Science.gov

Sample records for assessing drug distribution

  1. Multimodal assessment of spatial distribution of drug-tracer uptake by brain tissue after intra-arterial injections

    NASA Astrophysics Data System (ADS)

    Singh-Moon, Rajinder; Chaudhuri, Durba; Wang, Mei; Straubinger, Robert; Bigio, Irving J.; Joshi, Shailendra

    2014-02-01

    It is challenging to track the rapid changes in drug concentrations after intra-arterial (IA) administration to elucidate the pharmacokinetics of this method of drug delivery. Traditional pharmacokinetic parameters (such as protein binding) that are highly relevant to intravenous (IV) administration do not seem to apply to IA injections. Regional drug delivery is affected by the biomechanics of drug injection, resting blood flow, and local tissue extraction. In-vivo and ex-vivo, optical methods for spatial mapping of drug deposition can assist in visualizing drug distributions and aid in the screening of potential drugs and carrier candidates. We present a multimodal approach for the assessment of drug distribution in postmortem tissue specimens using diffuse reflectance spectroscopy, multispectral imaging, and confocal microscopy and demonstrate feasibility of distinguishing route of administration advantages of liposome-dye conjugate delivery. The results of this study suggest that insight on drug dynamics gained by this aggregated approach can be used to help screen and/or optimize potential drug candidates and drug delivery protocols.

  2. Simultaneous confocal fluorescence microscopy and optical coherence tomography for drug distribution and tissue integrity assessment

    NASA Astrophysics Data System (ADS)

    Rinehart, Matthew T.; LaCroix, Jeffrey; Henderson, Marcus; Katz, David; Wax, Adam

    2011-03-01

    The effectiveness of microbicidal gels, topical products developed to prevent infection by sexually transmitted diseases including HIV/AIDS, is governed by extent of gel coverage, pharmacokinetics of active pharmaceutical ingredients (APIs), and integrity of vaginal epithelium. While biopsies provide localized information about drug delivery and tissue structure, in vivo measurements are preferable in providing objective data on API and gel coating distribution as well as tissue integrity. We are developing a system combining confocal fluorescence microscopy with optical coherence tomography (OCT) to simultaneously measure local concentrations and diffusion coefficients of APIs during transport from microbicidal gels into tissue, while assessing tissue integrity. The confocal module acquires 2-D images of fluorescent APIs multiple times per second allowing analysis of lateral diffusion kinetics. The custom Fourier domain OCT module has a maximum a-scan rate of 54 kHz and provides depth-resolved tissue integrity information coregistered with the confocal fluorescence measurements. The combined system is validated by imaging phantoms with a surrogate fluorophore. Time-resolved API concentration measured at fixed depths is analyzed for diffusion kinetics. This multimodal system will eventually be implemented in vivo for objective evaluation of microbicide product performance.

  3. Drug distribution in enteric microparticles.

    PubMed

    Nilkumhang, Suchada; Alhnan, Mohamed A; McConnell, Emma L; Basit, Abdul W

    2009-09-01

    The aim of this study was to assess the distribution of three fluorescent drug or drug-like molecules in enteric microparticles. Microparticles were prepared using the pH-responsive methylmethacrylate polymer Eudragit L by an emulsion solvent evaporation process. In the process drug and polymer are dissolved in ethanol, and dispersed in a liquid paraffin external phase using sorbitan sesquioleate as stabiliser. The incorporation and distribution of riboflavin, dipyridamole and acridine orange into these microparticles were investigated using confocal laser scanning microscopy (CLSM). The influence of the physicochemical properties of the molecules (solubility in the inner phase, partition coefficient [ethanol/paraffin]) on the distribution, encapsulation efficiency and pH-responsive dissolution behaviour of the microparticles were examined. The drug that tended to partition in ethanol rather than liquid paraffin (riboflavin) was efficiently encapsulated and evenly distributed. In contrast, compounds which partitioned in favour of the liquid paraffin localised towards the surface of the microparticles and exhibited lower encapsulation efficiency (dipyridamole and acridine orange). All three sets of drug-loaded microparticles showed a limited release in acid (<10% release); drug distribution appeared to have a minimum effect on drug release. This microparticle technology has the potential to provide effective enteric drug release with a wide variety of molecules. PMID:19505543

  4. Vaginal drug distribution modeling.

    PubMed

    Katz, David F; Yuan, Andrew; Gao, Yajing

    2015-09-15

    This review presents and applies fundamental mass transport theory describing the diffusion and convection driven mass transport of drugs to the vaginal environment. It considers sources of variability in the predictions of the models. It illustrates use of model predictions of microbicide drug concentration distribution (pharmacokinetics) to gain insights about drug effectiveness in preventing HIV infection (pharmacodynamics). The modeling compares vaginal drug distributions after different gel dosage regimens, and it evaluates consequences of changes in gel viscosity due to aging. It compares vaginal mucosal concentration distributions of drugs delivered by gels vs. intravaginal rings. Finally, the modeling approach is used to compare vaginal drug distributions across species with differing vaginal dimensions. Deterministic models of drug mass transport into and throughout the vaginal environment can provide critical insights about the mechanisms and determinants of such transport. This knowledge, and the methodology that obtains it, can be applied and translated to multiple applications, involving the scientific underpinnings of vaginal drug distribution and the performance evaluation and design of products, and their dosage regimens, that achieve it. PMID:25933938

  5. Safety assessment of drug residues

    SciTech Connect

    Jackson, B.A.

    1980-05-15

    The safety assessment of drug residues is part of the process for defining the conditions for the safe use of drugs in food-producing animals. The information needed to assess the safety of drug residues is provided by chemical and toxicity tests. Toxicity tests are conducted to identify the type of effect produced and to determine the exposure concentrations that would be expected not to produce the effect. These tests include acute, subacute, and chronic toxicity tests, as well as reproduction studies and other special tests. The results are used to find an acceptable daily intake for drug residues that can be used to set a tolerance.

  6. Patterns of Drug Distribution: Implications and Issues#

    PubMed Central

    Johnson, Bruce D.

    2007-01-01

    This article delineates various patterns of illicit sales of drugs, especially at the retail (and near-retail) level, addressing a variety of central issues about drug sales and distribution documented during the past 30 years, including: a) the links between drug consumption and drug distribution activities; b) the various distribution roles; c) various levels of the distribution hierarchy; d) types of retail and wholesale markets; e) the association of drug distribution with nondrug associated criminality and violence. The article also will address the implications of drug distribution: whether various public policies such as supply reduction and source interdiction affect illicit drug markets, and how policing strategies and various law enforcement strategies can influence the involvement of individual participation in drug distribution activities. The overlooked contribution of treatment for “drug abuse” to reducing drug sales and distribution activities also will be considered as will other critical unresolved issues. PMID:14582578

  7. Distributed road assessment system

    DOEpatents

    Beer, N. Reginald; Paglieroni, David W

    2014-03-25

    A system that detects damage on or below the surface of a paved structure or pavement is provided. A distributed road assessment system includes road assessment pods and a road assessment server. Each road assessment pod includes a ground-penetrating radar antenna array and a detection system that detects road damage from the return signals as the vehicle on which the pod is mounted travels down a road. Each road assessment pod transmits to the road assessment server occurrence information describing each occurrence of road damage that is newly detected on a current scan of a road. The road assessment server maintains a road damage database of occurrence information describing the previously detected occurrences of road damage. After the road assessment server receives occurrence information for newly detected occurrences of road damage for a portion of a road, the road assessment server determines which newly detected occurrences correspond to which previously detected occurrences of road damage.

  8. Comparative assessment of four drug interaction compendia

    PubMed Central

    Vitry, Agnes I

    2007-01-01

    Aims To assess the consistency of inclusion and grading of major drug interactions for 50 drugs in four leading international drug interaction compendia. Methods Four international drug interaction compendia were compared: the drug interactions appendix of the British National Formulary, the interaction supplement in the French drug compendium Vidal, and two US drug interaction compendia, Drug Interaction Facts and the Micromedex (Drug-Reax) program. Major interactions were defined as potentially hazardous in BNF or with the warning ‘contraindication’ or ‘avoid’ in Vidal or with the significance grading 1 or 2 in DIF. Major interactions for a list of 50 drugs were searched in all four compendia. Results A total of 1264 interactions meeting the inclusion criteria were identified for these 50 drugs. After deletion of 169 duplicates, 1095 interactions were included in the analysis. Of the drug interactions classified as major in any one compendium between 14% and 44% were not listed in the other compendia. The grading systems used for the severity and the quality of the supporting evidence in Micromedex and DIF were inconsistent. Conclusions There is a lack of consistency in the inclusion and grading of drug interactions of major significance for 50 drugs across the four drug compendia examined. This may reflect the lack of standardization of the terminology used to classify drug interactions and the lack of good epidemiological evidence on which to base the assessment of the clinical relevance of drug interactions. PMID:17166171

  9. Environmental assessment requirements for live biological drugs.

    PubMed

    Sutton, Ann

    2008-02-01

    Marketing approval of biological products by the US Food and Drug Administration must comply with requirements of Code of Federal Regulations title 21 part 25, "Environmental Impact Considerations." An environmental impact statement is usually not required. Environmental assessment is required unless excluded. As naturally occurring substances, biological products qualify for categorical exclusion if manufacture and use do not significantly alter their concentration or distribution in the human environment. The manufacturing process and establishment descriptions in the license application should include enough detail to ensure that waste is controlled and inactivated. During clinical development of a live biotherapeutic product, data should be collected regarding the shedding of live organisms from treated patients. The ability of the live organism to persist in the environment should be assessed, and instructions for safe handling by health care providers and consumers should be incorporated into the package insert. PMID:18181713

  10. Multistep, effective drug distribution within solid tumors.

    PubMed

    Shemi, Amotz; Khvalevsky, Elina Zorde; Gabai, Rachel Malka; Domb, Abraham; Barenholz, Yechezkel

    2015-11-24

    The distribution of drugs within solid tumors presents a long-standing barrier for efficient cancer therapies. Tumors are highly resistant to diffusion, and the lack of blood and lymphatic flows suppresses convection. Prolonged, continuous intratumoral drug delivery from a miniature drug source offers an alternative to both systemic delivery and intratumoral injection. Presented here is a model of drug distribution from such a source, in a multistep process. At delivery onset the drug mainly affects the closest surroundings. Such 'priming' enables drug penetration to successive cell layers. Tumor 'void volume' (volume not occupied by cells) increases, facilitating lymphatic perfusion. The drug is then transported by hydraulic convection downstream along interstitial fluid pressure (IFP) gradients, away from the tumor core. After a week tumor cell death occurs throughout the entire tumor and IFP gradients are flattened. Then, the drug is transported mainly by 'mixing', powered by physiological bulk body movements. Steady state is achieved and the drug covers the entire tumor over several months. Supporting measurements are provided from the LODER™ system, releasing siRNA against mutated KRAS over months in pancreatic cancer in-vivo models. LODER™ was also successfully employed in a recent Phase 1/2 clinical trial with pancreatic cancer patients. PMID:26416413

  11. [Update of the French drug reaction assessment method].

    PubMed

    Arimone, Yannick; Bidault, Irène; Dutertre, Jean-Paul; Gérardin, Marie; Guy, Claire; Haramburu, Françoise; Hillaire-Buys, Dominique; Meglio, Carmine; Penfornis, Catherine; Théophile, Hélène; Valnet-Rabier, Marie-Blanche

    2011-01-01

    A tripartite group, entitled « CRI » (for Cercle de réflexion sur l'imputabilité), involving French pharmacovigilance staff from the French network of the Regional centers of pharmacovigilance, from pharmaceutical companies, and from French Health Authorities (Agence française de sécurité sanitaire des produits de santé) has worked to update the French drug reaction assessment method. Following assessment of strengths and weaknesses of the previous method, several points for improvement are proposed: a more precise wording and a more discriminating scale for some of the chronological and semiological criteria, a wider distribution of the intrinsic score from 5 to 7 levels, a new bibliographic scale for differentiating expected and unexpected adverse drug reactions, and a new informativness scale. This updated method would lead to a more relevant assessment of relationship between a drug and the occurrence of an adverse reaction. Furthermore, this method is a teaching tool to assess the level of relationship between a drug and the occurrence of an adverse reaction. PMID:22186077

  12. Pricing, distribution, and use of antimalarial drugs.

    PubMed

    Foster, S D

    1991-01-01

    Prices of new antimalarial drugs are targeted at the "travellers' market" in developed countries, which makes them unaffordable in malaria-endemic countries where the per capita annual drug expenditures are US$ 5 or less. Antimalarials are distributed through a variety of channels in both public and private sectors, the official malaria control programmes accounting for 25-30% of chloroquine distribution. The unofficial drug sellers in markets, streets, and village shops account for as much as half of antimalarials distributed in many developing countries. Use of antimalarials through the health services is often poor; drug shortages are common and overprescription and overuse of injections are significant problems. Anxiety over drug costs may prevent patients from getting the necessary treatment for malaria, especially because of the seasonal appearance of this disease when people's cash reserves are very low. The high costs may lead them to unofficial sources, which will sell a single tablet instead of a complete course of treatment, and subsequently to increased, often irrational demand for more drugs and more injections. Increasingly people are resorting to self-medication for malaria, which may cause delays in seeking proper treatment in cases of failure, especially in areas where chloroquine resistance has increased rapidly. Self-medication is now widespread, and measures to restrict the illicit sale of drugs have been unsuccessful. The "unofficial" channels thus represent an unacknowledged extension of the health services in many countries; suggestions are advanced to encourage better self-medication by increasing the knowledge base among the population at large (mothers, schoolchildren, market sellers, and shopkeepers), with an emphasis on correct dosing and on the importance of seeking further treatment without delay, if necessary. PMID:1893512

  13. Assessment of drug delivery devices.

    PubMed

    Batista, Elsa; Almeida, Nelson; Furtado, Andreia; Filipe, Eduarda; Sousa, Luis; Martins, Rui; Lucas, Peter; Petter, Harm Tido; Snijder, Roland; Timmerman, Annemoon

    2015-08-01

    For critical drug delivery, it is important to have a constant and well-known infusion rate delivered by the complete infusion set-up (pump, tubing, and accessories). Therefore, various drug delivery devices and accessories were tested in this article in terms of their infusion accuracy, start-up delay, response time, and dependency on the viscosity. These measurements were performed as part of the European funded research project MeDD. The obtained results show that the infusion accuracy of the devices is flow rate and accessory depended, especially for low flow rates. Viscosity does not have a significant impact on the flow rate accuracy. PMID:25945719

  14. Exploration of heterogeneity in distributed research network drug safety analyses.

    PubMed

    Hansen, Richard A; Zeng, Peng; Ryan, Patrick; Gao, Juan; Sonawane, Kalyani; Teeter, Benjamin; Westrich, Kimberly; Dubois, Robert W

    2014-12-01

    Distributed data networks representing large diverse populations are an expanding focus of drug safety research. However, interpreting results is difficult when treatment effect estimates vary across datasets (i.e., heterogeneity). In a previous study, risk estimates were generated for selected drugs and potential adverse outcomes. Analyses were replicated across eight distributed data sources using an identical analytic structure. To evaluate heterogeneity of risk estimates across data sources, the estimates were combined with summary-level data characterizing the population of each data source. Meta-analysis, meta-regression, and plots of the influence on overall results versus contribution to heterogeneity were examined and used to illustrate an approach to heterogeneity assessment. Heterogeneity, as measured by the I-squared statistic, was high with variability across outcomes. Plots of the relationship between influence on overall results and contribution to heterogeneity suggest that certain datasets and characteristics were influential but there was variability dependent on the drug and outcome being assessed. Exploratory meta-regression identified many possible influential factors, but may be subject to ecological bias and false positive conclusions. Distributed data network drug safety analyses can produce heterogeneous risk estimates that may not be easily explained. Approaches illustrated here can be useful for research that is subject to similar problems with heterogeneity. PMID:26052957

  15. 77 FR 44177 - Antimicrobial Animal Drug Sales and Distribution Reporting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-27

    ...DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 514 [Docket No. FDA-2012-N-0447] Antimicrobial Animal Drug Sales and Distribution Reporting AGENCY: Food and Drug Administration, HHS. ACTION: Advance...

  16. Appropriately assessing renal function for drug dosing.

    PubMed

    Dong, Kimberly; Quan, David J

    2010-01-01

    Chronic kidney disease affects millions of Americans. Many drugs are eliminated from the body by the kidneys. As renal function declines due to the disease, drugs that are normally eliminated by the kidneys can accumulate, potentially leading to toxicity. Assessing kidney function in patients is essential in determining the appropriate dose of medications to achieve the desired clinical outcome while minimizing the potential for toxicity. PMID:20629469

  17. Physiologically based pharmacokinetic modeling for assessing the clinical drug-drug interaction of alisporivir.

    PubMed

    Xia, Binfeng; Barve, Avantika; Heimbach, Tycho; Zhang, Tao; Gu, Helen; Wang, Lai; Einolf, Heidi; Alexander, Natalya; Hanna, Imad; Ke, June; Mangold, James B; He, Handan; Sunkara, Gangadhar

    2014-10-15

    Alisporivir is a novel cyclophilin-binding molecule with potent anti-hepatitis C virus (HCV) activity. In vitro data from human liver microsomes suggest that alisporivir is a substrate and a time-dependent inhibitor (TDI) of CYP3A4. The aim of the current work was to develop a novel physiologically based pharmacokinetic (PBPK) model to quantitatively assess the magnitude of CYP3A4 mediated drug-drug interactions with alisporivir as the substrate or victim drug. Towards that, a Simcyp PBPK model was developed by integrating in vitro data with in vivo clinical findings to characterize the clinical pharmacokinetics of alisporivir and further assess the magnitude of drug-drug interactions. Incorporated with absorption, distribution, elimination, and TDI data, the model accurately predicted AUC, Cmax, and tmax values after single or multiple doses of alisporivir with a prediction deviation within ± 32%. The model predicted an alisporivir AUC increase by 9.4-fold and a decrease by 86% when alisporivir was co-administrated with ketoconazole (CYP3A4 inhibitor) or rifampin (CYP3A4 inducer), respectively. Predictions were within ± 20% of the observed changes. In conclusion, the PBPK model successfully predicted the alisporivir PK and the magnitude of drug-drug interactions. PMID:25008118

  18. Distributed Assessment of Network Centrality

    E-print Network

    Wehmuth, Klaus

    2011-01-01

    We propose a method for the Distributed Assessment of Network CEntrality (DANCE) in complex networks. DANCE attributes to each node a volume-based centrality computed using only localized information, thus not requiring knowledge of the full network topology. We show DANCE is simple, yet efficient, in assessing node centrality in a distributed way. Our proposal also provides a way for locating the most central nodes, again using only the localized information at each node. We also show that the node rankings based on DANCE's centrality and the traditional closeness centrality correlate very well. This is quite useful given the vast potential applicability of closeness centrality, which is however limited by its high computational costs. We experimentally evaluate DANCE against a state-of-the-art proposal to distributively assess network centrality. Results attest that DANCE achieves similar effectiveness in assessing network centrality, but with a significant reduction in the associated costs for practical ap...

  19. 77 FR 44177 - Antimicrobial Animal Drug Sales and Distribution Reporting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-27

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 514 Antimicrobial Animal Drug Sales and Distribution Reporting AGENCY: Food and Drug Administration, HHS. ACTION: Advance notice of proposed rulemaking. SUMMARY: The Food and Drug Administration (FDA or Agency) is soliciting comments regarding...

  20. Drug interactions evaluation: An integrated part of risk assessment of therapeutics

    SciTech Connect

    Zhang, Lei; Reynolds, Kellie S.; Zhao, Ping; Huang, Shiew-Mei

    2010-03-01

    Pharmacokinetic drug interactions can lead to serious adverse events or decreased drug efficacy. The evaluation of a new molecular entity's (NME's) drug-drug interaction potential is an integral part of risk assessment during drug development and regulatory review. Alteration of activities of enzymes or transporters involved in the absorption, distribution, metabolism, or excretion of a new molecular entity by concomitant drugs may alter drug exposure, which can impact response (safety or efficacy). The recent Food and Drug Administration (FDA) draft drug interaction guidance ( (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072101.pdf)) highlights the methodologies and criteria that may be used to guide drug interaction evaluation by industry and regulatory agencies and to construct informative labeling for health practitioner and patients. In addition, the Food and Drug Administration established a 'Drug Development and Drug Interactions' website to provide up-to-date information regarding evaluation of drug interactions ( (http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm080499.htm)). This review summarizes key elements in the FDA drug interaction guidance and new scientific developments that can guide the evaluation of drug-drug interactions during the drug development process.

  1. 21 CFR 1310.10 - Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act. 1310.10 Section 1310.10 Food and Drugs DRUG ENFORCEMENT... Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act. (a)...

  2. 21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 9 2012-04-01 2012-04-01 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)...

  3. 21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 9 2011-04-01 2011-04-01 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)...

  4. 21 CFR 1310.10 - Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act. 1310.10 Section 1310.10 Food and Drugs DRUG ENFORCEMENT... Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act. (a)...

  5. 21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 9 2013-04-01 2013-04-01 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)...

  6. 21 CFR 1310.10 - Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act. 1310.10 Section 1310.10 Food and Drugs DRUG ENFORCEMENT... Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act. (a)...

  7. 21 CFR 1310.10 - Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act. 1310.10 Section 1310.10 Food and Drugs DRUG ENFORCEMENT... Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act. (a) The...

  8. 21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 9 2014-04-01 2014-04-01 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)...

  9. 21 CFR 1310.10 - Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act. 1310.10 Section 1310.10 Food and Drugs DRUG ENFORCEMENT... Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act. (a) The...

  10. 21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2010 CFR

    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)...

  11. Effects of cellular pharmacology on drug distribution in tissues.

    PubMed Central

    Rippley, R K; Stokes, C L

    1995-01-01

    The efficacy of targeted therapeutics such as immunotoxins is directly related to both the extent of distribution achievable and the degree of drug internalization by individual cells in the tissue of interest. The factors that influence the tissue distribution of such drugs include drug transport; receptor/drug binding; and cellular pharmacology, the processing and routing of the drug within cells. To examine the importance of cellular pharmacology, previously treated only superficially, we have developed a mathematical model for drug transport in tissues that includes drug and receptor internalization, recycling, and degradation, as well as drug diffusion in the extracellular space and binding to cell surface receptors. We have applied this "cellular pharmacology model" to a model drug/cell system, specifically, transferrin and the well-defined transferrin cycle in CHO cells. We compare simulation results to models with extracellular diffusion only or diffusion with binding to cell surface receptors and present a parameter sensitivity analysis. The comparison of models illustrates that inclusion of intracellular trafficking significantly increases the total transferrin concentration throughout much of the tissue while decreasing the penetration depth. Increasing receptor affinity or tissue receptor density reduces permeation of extracellular drug while increasing the peak value of the intracellular drug concentration, resulting in "internal trapping" of transferrin near the source; this could account for heterogeneity of drug distributions observed in experimental systems. Other results indicate that the degree of drug internalization is not predicted by the total drug profile. Hence, when intracellular drug is required for a therapeutic effect, the optimal treatment may not result from conditions that produce the maximal total drug distribution. Examination of models that include cellular pharmacology may help guide rational drug design and provide useful information for whole body pharmacokinetic studies. PMID:8519983

  12. 21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...exemption for drug products distributed under the Food, Drug and Cosmetic Act. 1310.11 Section 1310.11 Food and Drugs DRUG...exemption for drug products distributed under the Food, Drug and Cosmetic Act. (a) The Administrator has reinstated the...

  13. 21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...exemption for drug products distributed under the Food, Drug and Cosmetic Act. 1310.11 Section 1310.11 Food and Drugs DRUG...exemption for drug products distributed under the Food, Drug and Cosmetic Act. (a) The Administrator has reinstated the...

  14. 21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...exemption for drug products distributed under the Food, Drug and Cosmetic Act. 1310.11 Section 1310.11 Food and Drugs DRUG...exemption for drug products distributed under the Food, Drug and Cosmetic Act. (a) The Administrator has reinstated the...

  15. 21 CFR 1310.10 - Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act. 1310.10 Section 1310.10 Food and Drugs DRUG...exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act. (a) The Administrator may remove from...

  16. 21 CFR 1310.10 - Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act. 1310.10 Section 1310.10 Food and Drugs DRUG...exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act. (a) The Administrator may remove from...

  17. 21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...exemption for drug products distributed under the Food, Drug and Cosmetic Act. 1310.11 Section 1310.11 Food and Drugs DRUG...exemption for drug products distributed under the Food, Drug and Cosmetic Act. (a) The Administrator has reinstated the...

  18. 21 CFR 1310.10 - Removal of the exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act. 1310.10 Section 1310.10 Food and Drugs DRUG...exemption of drugs distributed under the Federal Food, Drug and Cosmetic Act. (a) The Administrator may remove from...

  19. 21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...exemption for drug products distributed under the Food, Drug and Cosmetic Act. 1310.11 Section 1310.11 Food and Drugs DRUG...exemption for drug products distributed under the Food, Drug and Cosmetic Act. (a) The Administrator has reinstated the...

  20. Distribution of veterinary drug residues among muscles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The U.S. Food and Drug Administration sets tolerances for veterinary drug residues in muscle, but does not specify which muscle should be sampled for analysis. The goal of this research was to determine if antibiotic residue levels are dependent on muscle type. In this study, penicillin G (Pen G) d...

  1. Assessment of the consistency among three drug compendia in listing and ranking of drug-drug interactions

    PubMed Central

    Nikoli?, Božana S.; Ili?, Maja S.

    2013-01-01

    Inconsistent information about drug-drug interactions can cause variations in prescribing, and possibly increase the incidence of morbidity and mortality. The aim of this study was to assess whether there is an inconsistency in drug-drug interaction listing and ranking in three authoritative, freely accessible online drug information sources: The British National Formulary; The Compendium about Drugs Licensed for Use in the United Kingdom (the Electronic Medicines Compendium) and the Compendium about Drugs Licensed for Use in the United States (the DailyMed). Information on drug-drug interactions for thirty drugs which have a high or medium potential for interactions have been selected for analysis. In total, 1971 drug-drug interactions were listed in all three drug information sources, of these 992 were ranked as the interactions with the potential of clinical significance. Comparative analysis identified that 63.98% of interactions were listed in only one drug information source, and 66.63% of interactions were ranked in only one drug information source. Only 15.12% listed and 11.19% ranked interactions were identified in all three information sources. Intraclass correlation coefficient indicated a weak correlation among the three drug information sources in listing (0.366), as well as in ranking drug interactions (0.467). This study showed inconsistency of information on drug-drug interaction for the selected drugs in three authoritative, freely accessible online drug information sources. The application of a uniform methodology in assessment of information, and then the presentation of information in a standardized format is required to prevent and adequately manage drug-drug interactions. PMID:24289762

  2. 77 FR 20025 - Draft Guidance for Industry on Compliance Policy for Reporting Drug Sample Distribution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-03

    ... Sample Distribution Information; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice... industry entitled ``Compliance Policy on Reporting Drug Sample Distribution Information Under the... ``Compliance Policy on Reporting Drug Sample Distribution Information.'' On March 23, 2010, the Affordable...

  3. Assessing Website Pharmacy Drug Quality: Safer Than You Think?

    PubMed Central

    Bate, Roger; Hess, Kimberly

    2010-01-01

    Background Internet-sourced drugs are often considered suspect. The World Health Organization reports that drugs from websites that conceal their physical address are counterfeit in over 50 percent of cases; the U.S. Food and Drug Administration (FDA) works with the National Association of Boards of Pharmacy (NABP) to regularly update a list of websites likely to sell drugs that are illegal or of questionable quality. Methods and Findings This study examines drug purchasing over the Internet, by comparing the sales of five popular drugs from a selection of websites stratified by NABP or other ratings. The drugs were assessed for price, conditions of purchase, and basic quality. Prices and conditions of purchase varied widely. Some websites advertised single pills while others only permitted the purchase of large quantities. Not all websites delivered the exact drugs ordered, some delivered no drugs at all; many websites shipped from multiple international locations, and from locations that were different from those advertised on the websites. All drug samples were tested against approved U.S. brand formulations using Raman spectrometry. Many (17) websites substituted drugs, often in different formulations from the brands requested. These drugs, some of which were probably generics or perhaps non-bioequivalent copy versions, could not be assessed accurately. Of those drugs that could be assessed, none failed from “approved”, “legally compliant” or “not recommended” websites (0 out of 86), whereas 8.6% (3 out of 35) failed from “highly not recommended” and unidentifiable websites. Conclusions Of those drugs that could be assessed, all except Viagra® passed spectrometry testing. Of those that failed, few could be identified either by a country of manufacture listed on the packaging, or by the physical location of the website pharmacy. If confirmed by future studies on other drug samples, then U.S. consumers should be able to reduce their risk by relying on credentialing agencies recommended lists and by using common sense when examining packaging and pills. PMID:20730049

  4. Photophysical probes to assess the potential of cholic acid aggregates as drug carriers.

    PubMed

    Gomez-Mendoza, Miguel; Nuin, Edurne; Andreu, Inmaculada; Marin, M Luisa; Miranda, Miguel A

    2012-08-30

    The two enantiomers of the nonsteroidal antiinflammatory drug naproxen and of its methyl ester have been selected as representative probes with markedly different hydrophobicity to assess the potential of cholic acid aggregates as drug carriers by means of photophysical techniques. The different distribution of the probes between bulk solution and aggregates has been assessed by quenching of their singlet and triplet excited states by iodide and nitrite anions, respectively. This straightforward photophysical methodology can, in principle, be extended to a variety of drugs containing a photoactive chromophore. PMID:22882252

  5. Implicit and Explicit Drug-Related Cognitions during Detoxification Treatment Are Associated with Drug Relapse: An Ecological Momentary Assessment Study

    ERIC Educational Resources Information Center

    Marhe, Reshmi; Waters, Andrew J.; van de Wetering, Ben J. M.; Franken, Ingmar H. A.

    2013-01-01

    Objective: Relapse is a major problem in drug addiction treatment. Both drug craving and drug-related cognitions (e.g., attentional bias and implicit attitudes to drugs) may contribute to relapse. Using ecological momentary assessments, we examined whether craving and cognitions assessed during drug detoxification treatment were associated with…

  6. 21 CFR 1310.10 - Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    21 Food and Drugs 9 2010-04-01 2010-04-01 false Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act. 1310.10 Section 1310.10 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION,...

  7. 21 CFR 1310.10 - Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    21 Food and Drugs 9 2011-04-01 2011-04-01 false Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act. 1310.10 Section 1310.10 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION,...

  8. DISSERTATION Spatially Distributed Model to Assess Watershed

    E-print Network

    Julien, Pierre Y.

    DISSERTATION Spatially Distributed Model to Assess Watershed Contaminant Transport and Fate OF DISSERTATION SPATIALLY DISTRIBUTED MODEL TO ASSESS WATERSHED CONTAMINANT TRANSPORT AND FATE Unmanaged to simulate chemical transport and fate at the watershed scale. In addition to runoff and sediment transport

  9. A reliability assessment methodology for distribution systems with distributed generation 

    E-print Network

    Duttagupta, Suchismita Sujaya

    2006-08-16

    Reliability assessment is of primary importance in designing and planning distribution systems that operate in an economic manner with minimal interruption of customer loads. With the advances in renewable energy sources, ...

  10. Experienced drug users assess the relative harms and benefits of drugs: a web-based survey.

    PubMed

    Carhart-Harris, Robin Lester; Nutt, David John

    2013-01-01

    A web-based survey was used to consult the opinions of experienced drug users on matters related to drug harms. We identified a rare sample of 93 drug users with personal experience with 11 different illicit drugs that are widely used in the UK. Asked to assess the relative harms of these drugs, they ranked alcohol and tobacco as the most harmful, and three "Class A" drugs (MDMA, LSD, and psilocybin) and one class B (cannabis) were ranked as the four least harmful drugs. When asked to assess the relative potential for benefit of the 11 drugs, MDMA, LSD, psilocybin, and cannabis were ranked in the top four; and when asked why these drugs are beneficial, rather than simply report hedonic properties, they referred to potential therapeutic applications (e.g., as tools to assist psychotherapy). These results provide a useful insight into the opinions of experienced drug users on a subject about which they have a rare and intimate knowledge. PMID:24377171

  11. Laser speckle imaging of intra organ drug distribution

    PubMed Central

    Postnov, Dmitry D; Holstein-Rathlou, Niels-Henrik; Sosnovtseva, Olga

    2015-01-01

    Laminar flow in arteries causes streaming and uneven distribution of infused agents within the organ. This may lead to misinterpretation of experimental results and affect treatment outcomes. We monitor dynamical changes of superficial cortical blood flow in the rat kidney following different routes of administration of the vasoconstrictor angiotensin II. Our analysis reveals the appearance of large scale oscillations of the blood flow caused by inhomogeneous intra organ drug distribution. PMID:26713217

  12. Laser speckle imaging of intra organ drug distribution.

    PubMed

    Postnov, Dmitry D; Holstein-Rathlou, Niels-Henrik; Sosnovtseva, Olga

    2015-12-01

    Laminar flow in arteries causes streaming and uneven distribution of infused agents within the organ. This may lead to misinterpretation of experimental results and affect treatment outcomes. We monitor dynamical changes of superficial cortical blood flow in the rat kidney following different routes of administration of the vasoconstrictor angiotensin II. Our analysis reveals the appearance of large scale oscillations of the blood flow caused by inhomogeneous intra organ drug distribution. PMID:26713217

  13. Designer drugs 2015: assessment and management.

    PubMed

    Weaver, Michael F; Hopper, John A; Gunderson, Erik W

    2015-01-01

    Recent designer drugs, also known as "legal highs," include substituted cathinones (e.g., mephedrone, methylone, and methylenedioxypyrovalerone, often referred to as "bath salts"); synthetic cannabinoids (SCs; e.g., Spice); and synthetic hallucinogens (25I-NBOMe, or N-bomb). Compound availability has evolved rapidly to evade legal regulation and detection by routine drug testing. Young adults are the primary users, but trends are changing rapidly; use has become popular among members of the military. Acute toxicity is common and often manifests with a constellation of psychiatric and medical effects, which may be severe (e.g., anxiety, agitation, psychosis, and tachycardia), and multiple deaths have been reported with each of these types of designer drugs. Clinicians should keep designer drugs in mind when evaluating substance use in young adults or in anyone presenting with acute neuropsychiatric complaints. Treatment of acute intoxication involves supportive care targeting manifesting signs and symptoms. Long-term treatment of designer drug use disorder can be challenging and is complicated by a lack of evidence to guide treatment. PMID:25928069

  14. [Assessment of the legal awareness regarding drug consumption].

    PubMed

    Morawska, Jowanka; Satora, Leszek

    2004-01-01

    The latest legislation against drug addiction has changed the approach of Pursuing Organs in Poland to the problem of taking and distribution of drugs. Many tests have been carried out in order to evaluate the extent of legal regulations as the appropriate instrument in the struggle against drug addiction. The survey and interview were introduced during the research. The results make it possible to form the following conclusions. Law, only as a supplementary means supporting other methods may help prevent and counteract the addictions. Legal regulation on drug addiction which are based on compulsion and punishment should be widely taken into account. PMID:15521595

  15. 21 CFR 203.50 - Requirements for wholesale distribution of prescription drugs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Requirements for wholesale distribution of... HUMAN SERVICES (CONTINUED) DRUGS: GENERAL PRESCRIPTION DRUG MARKETING Wholesale Distribution § 203.50 Requirements for wholesale distribution of prescription drugs. (a) Identifying statement for sales...

  16. 21 CFR 203.50 - Requirements for wholesale distribution of prescription drugs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Requirements for wholesale distribution of... HUMAN SERVICES (CONTINUED) DRUGS: GENERAL PRESCRIPTION DRUG MARKETING Wholesale Distribution § 203.50 Requirements for wholesale distribution of prescription drugs. (a) Identifying statement for sales...

  17. Use of radioactive compounds and autoradiography to determine drug tissue distribution.

    PubMed

    Solon, Eric G

    2012-03-19

    Radioactivity has been used in drug discovery and development for several decades because it offers researchers a highly sensitive way to quantitatively assess the absorption, distribution, metabolism, and/or excretion (ADME) of chemical entities by incorporating a radioactive isotope into the structure of the drug molecule. Regulatory agencies around the world require drug makers to characterize the ADME properties of prospective new drugs as one way to help ensure that patients are not exposed to dangerous drug and/or drug metabolite levels before they can be approved for human use. Radiolabeled compounds have consistently proved to be the most efficient tool for determining that information, even though attempts have been made to use nonradioactive techniques. The techniques of quantitative whole-body autoradiography (QWBA) and microautoradiography (MARG), which rely on the use of radiolabeled drugs, are two techniques that are routinely used to examine tissue distribution of drugs in discovery and development. These techniques provide drug researchers with quantitative tissue concentration data and a visual location of those concentrations in intact organs, tissues, and cells of laboratory animals. It is important for readers to realize that these techniques visualize total radioactivity, which can include the parent molecule along with its metabolites, and/or degradation products or impurities. This requires investigators to treat the quantitative data with caution unless the identity of the radioactivity is determined using some type of other bioanalytical techniques, such as mass spectroscopy and/or radio-HPLC, which can be easily performed on the tissue obtained from the animals used for QWBA and/or MARG. Nevertheless, these data are used in drug discovery and development to answer questions related to tissue penetration, fetal/placental transfer, tissue retention, routes of elimination, drug-drug interactions, enzyme induction/inhibition, formulation comparisons, in vivo compound solubility, differential metabolite distribution, interspecies comparisons, and to predict human exposure to parent drugs, metabolites, and radiation during clinical studies. This review will consider the strategic use of WBA, QWBA, and MARG in the pharmaceutical industry. Case studies and anecdotal information will also be presented; however, readers should realize that these are general examples and that some details have been omitted for brevity and/or because the data is proprietary and could not be presented at this time. Nevertheless, the images and discussions are provided to demonstrate how the techniques can and have been used to examine in situ tissue distribution of therapeutic compounds. PMID:22280496

  18. microRNAs as pharmacogenomic biomarkers for drug efficacy and drug safety assessment.

    PubMed

    Koturbash, Igor; Tolleson, William H; Guo, Lei; Yu, Dianke; Chen, Si; Hong, Huixiao; Mattes, William; Ning, Baitang

    2015-11-01

    Much evidence has documented that microRNAs (miRNAs) play an important role in the modulation of interindividual variability in the production of drug metabolizing enzymes and transporters (DMETs) and nuclear receptors (NRs) through multidirectional interactions involving environmental stimuli/stressors, the expression of miRNA molecules and genetic polymorphisms. MiRNA expression has been reported to be affected by drugs and miRNAs themselves may affect drug metabolism and toxicity. In cancer research, miRNA biomarkers have been identified to mediate intrinsic and acquired resistance to cancer therapies. In drug safety assessment, miRNAs have been found associated with cardiotoxicity, hepatotoxicity and nephrotoxicity. This review article summarizes published studies to show that miRNAs can serve as early biomarkers for the evaluation of drug efficacy and drug safety. PMID:26501795

  19. High-Throughput Cytochrome P450 Cocktail Inhibition Assay for Assessing Drug-Drug and Drug-Botanical Interactions.

    PubMed

    Li, Guannan; Huang, Ke; Nikolic, Dejan; van Breemen, Richard B

    2015-11-01

    Detection of drug-drug interactions is essential during the early stages of drug discovery and development, and the understanding of drug-botanical interactions is important for the safe use of botanical dietary supplements. Among the different forms of drug interactions that are known, inhibition of cytochrome P450 (P450) enzymes is the most common cause of drug-drug or drug-botanical interactions. Therefore, a rapid and comprehensive mass spectrometry-based in vitro high-throughput P450 cocktail inhibition assay was developed that uses 10 substrates simultaneously against nine CYP isoforms. Including probe substrates for CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and two probes targeting different binding sites of CYP3A4/5, this cocktail simultaneously assesses at least as many P450 enzymes as previous assays while remaining among the fastest due to short incubation times and rapid analysis using ultrahigh pressure liquid chromatography-tandem mass spectrometry. The method was validated using known inhibitors of each P450 enzyme and then shown to be useful not only for single-compound testing but also for the evaluation of potential drug-botanical interactions using the botanical dietary supplement licorice (Glycyrrhiza glabra) as an example. PMID:26285764

  20. 78 FR 59308 - Antimicrobial Animal Drug Sales and Distribution Annual Summary Report Data Tables

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-26

    ...OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 514 [Docket...FDA-2012-N-0447] Antimicrobial Animal Drug Sales and Distribution Annual Summary Report Data Tables AGENCY: Food and Drug Administration, HHS. ACTION:...

  1. A hybrid approach to advancing quantitative prediction of tissue distribution of basic drugs in human

    SciTech Connect

    Poulin, Patrick; Ekins, Sean; Theil, Frank-Peter

    2011-01-15

    A general toxicity of basic drugs is related to phospholipidosis in tissues. Therefore, it is essential to predict the tissue distribution of basic drugs to facilitate an initial estimate of that toxicity. The objective of the present study was to further assess the original prediction method that consisted of using the binding to red blood cells measured in vitro for the unbound drug (RBCu) as a surrogate for tissue distribution, by correlating it to unbound tissue:plasma partition coefficients (Kpu) of several tissues, and finally to predict volume of distribution at steady-state (V{sub ss}) in humans under in vivo conditions. This correlation method demonstrated inaccurate predictions of V{sub ss} for particular basic drugs that did not follow the original correlation principle. Therefore, the novelty of this study is to provide clarity on the actual hypotheses to identify i) the impact of pharmacological mode of action on the generic correlation of RBCu-Kpu, ii) additional mechanisms of tissue distribution for the outlier drugs, iii) molecular features and properties that differentiate compounds as outliers in the original correlation analysis in order to facilitate its applicability domain alongside the properties already used so far, and finally iv) to present a novel and refined correlation method that is superior to what has been previously published for the prediction of human V{sub ss} of basic drugs. Applying a refined correlation method after identifying outliers would facilitate the prediction of more accurate distribution parameters as key inputs used in physiologically based pharmacokinetic (PBPK) and phospholipidosis models.

  2. 21 CFR 212.90 - What actions must I take to control the distribution of PET drug products?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., purity, or quality of the PET drug product. (b) Distribution records. You must maintain distribution... distribution of PET drug products? 212.90 Section 212.90 Food and Drugs FOOD AND DRUG ADMINISTRATION... distribution of PET drug products? (a) Written distribution procedures. You must establish, maintain,...

  3. In Vivo Methods for the Assessment of Topical Drug Bioavailability

    PubMed Central

    Herkenne, Christophe; Alberti, Ingo; Naik, Aarti; Kalia, Yogeshvar N.; Mathy, François-Xavier; Préat, Véronique

    2007-01-01

    This paper reviews some current methods for the in vivo assessment of local cutaneous bioavailability in humans after topical drug application. After an introduction discussing the importance of local drug bioavailability assessment and the limitations of model-based predictions, the focus turns to the relevance of experimental studies. The available techniques are then reviewed in detail, with particular emphasis on the tape stripping and microdialysis methodologies. Other less developed techniques, including the skin biopsy, suction blister, follicle removal and confocal Raman spectroscopy techniques are also described. PMID:17985216

  4. 21 CFR 1405.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false To whom must I distribute my drug-free workplace statement? 1405.210 Section 1405.210 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements for Recipients Other Than Individuals § 1405.210 To whom must...

  5. Layered double hydroxide nanocomposite for drug delivery systems; bio-distribution, toxicity and drug activity enhancement.

    PubMed

    Kura, Aminu Umar; Hussein, Mohd Zobir; Fakurazi, Sharida; Arulselvan, Palanisamy

    2014-01-01

    The production of layered double hydroxide(LDH) nanocomposite as an alternative drug delivery system against various ailments is on the increase. Their toxicity potential is usually dose and time dependent with particle sizes, shapes and surface charge playing some role both in the in vitro and in vivo studies. The reticular endothelial system of especially the liver and spleen were shown to sequestrate most of these nanocomposite, especially those with sizes greater than 50 nm. The intracellular drug delivery by these particles is mainly via endocytotic pathways aided by the surface charges in most cases. However, structural modification of these nanocomposite via coating using different types of material may lower the toxicity where present. More importantly, the coating may serve as targeting ligand hence, directing drug distribution and leading to proper drug delivery to specific area of need; it equally decreases the unwanted nanocomposite accumulation in especially the liver and spleen. These nanocomposite have the advantage of wider bio-distribution irrespective of route of administration, excellent targeted delivery potential with ease of synthetic modification including coating. PMID:25177361

  6. Assessment of drug interactions relevant to pharmacodynamic indirect response models.

    PubMed

    Earp, Justin; Krzyzanski, Wojciech; Chakraborty, Abhijit; Zamacona, Miren K; Jusko, William J

    2004-10-01

    The assessment of drug interactions for a simple turnover system when the basic pharmacodynamic response is governed by indirect mechanisms was explored. This report describes a diverse array of possible in vivo pharmacodynamic effects from a combination of two drugs acting by similar or different indirect mechanisms. Various conditions of pharmacodynamic drug combinations were explored mathematically and by simulation: (a) interactions of two drugs acting simultaneously either on the production (k(in)) or on the dissipation (k(out)) processes controlling the in vivo response by competitive (four cases) or non-competitive interaction (six cases); and (b) combinations of two drugs acting on separate k(in) and k(out) processes simultaneously (four cases). A range of different combinations of drug doses was used. Plasma concentration time profiles were generated according to monoexponential disposition. Pharmacodynamic response profiles were simulated using the above conditions and characterized by descriptors such as Area Between Effect (and Baseline) Curve (ABEC) values. The interaction of agents by competitive mechanisms produced net responses that were additive in nature. Response profiles for non-competitive interactions on the same process were both antagonistic (for two drugs with effects that oppose each other) and synergistic (for two drugs that produce the same response). On the other hand, response signatures for agents acting non-competitively on the production and dissipation factors by opposing mechanisms (e.g. inhibiting k(in) plus stimulating k(out)) showed dramatic changes in net effects and produced apparent drug synergy. Net indirect response profiles for joint use of two or more drugs measured by ABEC values may look "additive", "antagonistic", or "synergistic" depending on doses, their intrinsic potencies, the nature of interaction (competitive or non-competitive) as well as their mechanisms of action. These models may help explain changes in pharmacologic responses to two agents in a more rational and mechanistic fashion than older empirical methods. PMID:15669772

  7. Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals

    PubMed Central

    Winand, Raf; Theys, Kristof; Eusébio, Mónica; Aerts, Jan; Camacho, Ricardo J.; Gomes, Perpetua; Suchard, Marc A.; Vandamme, Anne-Mieke; Abecasis, Ana B.

    2015-01-01

    Objectives: Surveillance drug resistance mutations (SDRMs) in drug-naive patients are typically used to survey HIV-1-transmitted drug resistance (TDR). We test here how SDRMs in patients failing treatment, the original source of TDR, contribute to assessing TDR, transmissibility and transmission source of SDRMs. Design: This is a retrospective observational study analyzing a Portuguese cohort of HIV-1-infected patients. Methods: The prevalence of SDRMs to protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) in drug-naive and treatment-failing patients was measured for 3554 HIV-1 subtype B patients. Transmission ratio (prevalence in drug-naive/prevalence in treatment-failing patients), average viral load and robust linear regression with outlier detection (prevalence in drug-naive versus in treatment-failing patients) were analyzed and used to interpret transmissibility. Results: Prevalence of SDRMs in drug-naive and treatment-failing patients were linearly correlated, but some SDRMs were classified as outliers – above (PRO: D30N, N88D/S, L90?M, RT: G190A/S/E) or below (RT: M184I/V) expectations. The normalized regression slope was 0.073 for protease inhibitors, 0.084 for NRTIs and 0.116 for NNRTIs. Differences between SDRMs transmission ratios were not associated with differences in viral loads. Conclusion: The significant linear correlation between prevalence of SDRMs in drug-naive and in treatment-failing patients indicates that the prevalence in treatment-failing patients can be useful to predict levels of TDR. The slope is a cohort-dependent estimate of rate of TDR per drug class and outlier detection reveals comparative persistence of SDRMs. Outlier SDRMs with higher transmissibility are more persistent and more likely to have been acquired from drug-naive patients. Those with lower transmissibility have faster reversion dynamics after transmission and are associated with acquisition from treatment-failing patients. PMID:26355575

  8. 21 CFR 212.90 - What actions must I take to control the distribution of PET drug products?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... affect the identity, purity, or quality of the PET drug product. (b) Distribution records. You must... distribution of PET drug products? 212.90 Section 212.90 Food and Drugs FOOD AND DRUG ADMINISTRATION... control the distribution of PET drug products? (a) Written distribution procedures. You must...

  9. An algorithm for evaluating potential tissue drug distribution in toxicology studies from readily available pharmacokinetic parameters.

    PubMed

    Poulin, Patrick; Dambach, Donna M; Hartley, Dylan H; Ford, Kevin; Theil, Frank-Peter; Harstad, Eric; Halladay, Jason; Choo, Edna; Boggs, Jason; Liederer, Bianca M; Dean, Brian; Diaz, Dolores

    2013-10-01

    Having an understanding of drug tissue accumulation can be informative in the assessment of target organ toxicities; however, obtaining tissue drug levels from toxicology studies by bioanalytical methods is labor-intensive and infrequently performed. Additionally, there are no described methods for predicting tissue drug distribution for the experimental conditions in toxicology studies, which typically include non-steady-state conditions and very high exposures that may saturate several processes. The aim was the development of an algorithm to provide semiquantitative and quantitative estimates of tissue-to-plasma concentration ratios (Kp ) for several tissues from readily available parameters of pharmacokinetics (PK) such as volume of distribution (Vd ) and clearance of each drug, without performing tissue measurement in vivo. The computational approach is specific for the oral route of administration and non-steady-state conditions and was applied for a dataset of 29 Genentech small molecules such as neutral compounds as well as weak and strong organic bases. The maximum success rate in predicting Kp values within 2.5-fold error of observed Kp values was 82% at low doses (<100 mg/kg) in preclinical species. Prediction accuracy was relatively lower with saturation at high doses (?100 mg/kg); however, an approach to perform low-to-high dose extrapolations of Kp values was presented and applied successfully in most cases. An approach for the interspecies scaling was also applied successfully. Finally, the proposed algorithm was used in a case study and successfully predicted differential tissue distribution of two small-molecule MET kinase inhibitors, which had different toxicity profiles in mice. This newly developed algorithm can be used to predict the partition coefficients Kp for small molecules in toxicology studies, which can be leveraged to optimize the PK drivers of tissue distribution in an attempt to decrease drug tissue level, and improve safety margins. PMID:23878104

  10. Critical Assessment of Implantable Drug Delivery Devices in Glaucoma Management

    PubMed Central

    Manickavasagam, Dharani; Oyewumi, Moses O.

    2013-01-01

    Glaucoma is a group of heterogeneous disorders involving progressive optic neuropathy that can culminate into visual impairment and irreversible blindness. Effective therapeutic interventions must address underlying vulnerability of retinal ganglion cells (RGCs) to degeneration in conjunction with correcting other associated risk factors (such as elevated intraocular pressure). However, realization of therapeutic outcomes is heavily dependent on suitable delivery system that can overcome myriads of anatomical and physiological barriers to intraocular drug delivery. Development of clinically viable sustained release systems in glaucoma is a widely recognized unmet need. In this regard, implantable delivery systems may relieve the burden of chronic drug administration while potentially ensuring high intraocular drug bioavailability. Presently there are no FDA-approved implantable drug delivery devices for glaucoma even though there are several ongoing clinical studies. The paper critically assessed the prospects of polymeric implantable delivery systems in glaucoma while identifying factors that can dictate (a) patient tolerability and acceptance, (b) drug stability and drug release profiles, (c) therapeutic efficacy, and (d) toxicity and biocompatibility. The information gathered could be useful in future research and development efforts on implantable delivery systems in glaucoma. PMID:24066234

  11. Technology assessment and the Food and Drug Administration

    NASA Technical Reports Server (NTRS)

    Kaplan, A. H.; Becker, R. H.

    1972-01-01

    The statutory standards underlying the activities of the FDA, and the problems the Agency faces in decision making are discussed from a legal point of view. The premarketing clearance of new drugs and of food additives, the two most publicized and criticized areas of FDA activity, are used as illustrations. The importance of statutory standards in technology assessment in a regulatory setting is developed. The difficulties inherent in the formulation of meaningful standards are recognized. For foods, the words of the statute are inadequate, and for drugs, a statutory recognition of the various other objectives would be useful to the regulator and the regulated.

  12. Risk assessment of drug-induced QT prolongation

    PubMed Central

    Isbister, Geoffrey K

    2015-01-01

    SUMMARY Drugs can cause prolongation of the QT interval, alone or in combination, potentially leading to fatal arrhythmias such as torsades de pointes. When prescribing drugs that prolong the QT interval, the balance of benefit versus harm should always be considered. Readouts from automated ECG machines are unreliable. The QT interval should be measured manually. Changes in heart rate influence the absolute QT interval. Heart rate correction formulae are inaccurate, particularly for fast and slow heart rates. The QT nomogram, a plot of QT interval versus heart rate, can be used as a risk assessment tool to detect an abnormal QT interval. PMID:26648606

  13. Probabilistic modeling of percutaneous absorption for risk-based exposure assessments and transdermal drug delivery.

    SciTech Connect

    Ho, Clifford Kuofei

    2004-06-01

    Chemical transport through human skin can play a significant role in human exposure to toxic chemicals in the workplace, as well as to chemical/biological warfare agents in the battlefield. The viability of transdermal drug delivery also relies on chemical transport processes through the skin. Models of percutaneous absorption are needed for risk-based exposure assessments and drug-delivery analyses, but previous mechanistic models have been largely deterministic. A probabilistic, transient, three-phase model of percutaneous absorption of chemicals has been developed to assess the relative importance of uncertain parameters and processes that may be important to risk-based assessments. Penetration routes through the skin that were modeled include the following: (1) intercellular diffusion through the multiphase stratum corneum; (2) aqueous-phase diffusion through sweat ducts; and (3) oil-phase diffusion through hair follicles. Uncertainty distributions were developed for the model parameters, and a Monte Carlo analysis was performed to simulate probability distributions of mass fluxes through each of the routes. Sensitivity analyses using stepwise linear regression were also performed to identify model parameters that were most important to the simulated mass fluxes at different times. This probabilistic analysis of percutaneous absorption (PAPA) method has been developed to improve risk-based exposure assessments and transdermal drug-delivery analyses, where parameters and processes can be highly uncertain.

  14. Drug-likeness analysis of traditional Chinese medicines: 1. property distributions of drug-like compounds, non-drug-like compounds and natural compounds from traditional Chinese medicines

    PubMed Central

    2012-01-01

    Background In this work, we analyzed and compared the distribution profiles of a wide variety of molecular properties for three compound classes: drug-like compounds in MDL Drug Data Report (MDDR), non-drug-like compounds in Available Chemical Directory (ACD), and natural compounds in Traditional Chinese Medicine Compound Database (TCMCD). Results The comparison of the property distributions suggests that, when all compounds in MDDR, ACD and TCMCD with molecular weight lower than 600 were used, MDDR and ACD are substantially different while TCMCD is much more similar to MDDR than ACD. However, when the three subsets of ACD, MDDR and TCMCD with similar molecular weight distributions were examined, the distribution profiles of the representative physicochemical properties for MDDR and ACD do not differ significantly anymore, suggesting that after the dependence of molecular weight is removed drug-like and non-drug-like molecules cannot be effectively distinguished by simple property-based filters; however, the distribution profiles of several physicochemical properties for TCMCD are obviously different from those for MDDR and ACD. Then, the performance of each molecular property on predicting drug-likeness was evaluated. No single molecular property shows good performance to discriminate between drug-like and non-drug-like molecules. Compared with the other descriptors, fractional negative accessible surface area (FASA-) performs the best. Finally, a PCA-based scheme was used to visually characterize the spatial distributions of the three classes of compounds with similar molecular weight distributions. Conclusion If FASA- was used as a drug-likeness filter, more than 80% molecules in TCMCD were predicted to be drug-like. Moreover, the principal component plots show that natural compounds in TCMCD have different and even more diverse distributions than either drug-like compounds in MDDR or non-drug-like compounds in ACD. PMID:23181938

  15. 29 CFR 94.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 1 2013-07-01 2013-07-01 false To whom must I distribute my drug-free workplace statement? 94.210 Section 94.210 Labor Office of the Secretary of Labor GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements for Recipients Other Than Individuals § 94.210 To whom must I distribute my drug-free...

  16. 29 CFR 94.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 1 2012-07-01 2012-07-01 false To whom must I distribute my drug-free workplace statement? 94.210 Section 94.210 Labor Office of the Secretary of Labor GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements for Recipients Other Than Individuals § 94.210 To whom must I distribute my drug-free...

  17. 22 CFR 312.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 2 2011-04-01 2009-04-01 true To whom must I distribute my drug-free workplace statement? 312.210 Section 312.210 Foreign Relations PEACE CORPS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements for Recipients Other Than Individuals § 312.210 To whom must I distribute my drug-free...

  18. 29 CFR 94.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 1 2011-07-01 2011-07-01 false To whom must I distribute my drug-free workplace statement? 94.210 Section 94.210 Labor Office of the Secretary of Labor GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements for Recipients Other Than Individuals § 94.210 To whom must I distribute my drug-free...

  19. Drug distribution in wet granulation: foam versus spray.

    PubMed

    Tan, Melvin X L; Nguyen, Thanh H; Hapgood, Karen P

    2013-09-01

    Foam granulation technology is a new wet granulation approach for pharmaceutical formulations. This study evaluates the performance of foam and spray granulation in achieving uniform drug distribution using a model formulation. To observe wetting and nuclei formation, single drop/foam penetration experiments were performed on a static powder bed comprised of varying compositions of hydrophilic/hydrophobic glass ballotini, and hydrophilic lactose/hydrophobic salicylic acid respectively. High shear granulation experiments were performed in a 5L mixer using varying compositions of hydrophilic lactose and hydrophobic salicylic acid. Four percent hydroxylpropyl methylcellulose (HPMC) solution was delivered at 90?g/min as either a foam (92% FQ) or an atomized spray whilst recording impeller power consumption. After drying, the granule size distribution was measured and the granule composition was estimated using gravimetric filtration in methanol. Foam penetration was less dependent on the powder hydrophobicity compared to drop penetration. For glass ballotini powder mixtures, foam induced nucleation created nuclei with relatively uniform structure and size regardless of the powder hydrophobicity. For salicylic acid and lactose mixtures, increasing the proportion of salicylic acid reduced the nuclei granule size for both foam and drop binder addition. The granule drug distribution was not significantly affected by the binder addition method. Processing conditions, including liquid binder amount, impeller speed, wet massing, and the wettability properties of the formulation were the dominant factors for delivering homogeneous granules. The study reveals that foam and spray granulation involve different nucleation mechanisms - spray tends to incur early liquid penetration whereas foam granulation operates well in mechanical dispersion. PMID:23057532

  20. Statistical assessment of Monte Carlo distributional tallies

    SciTech Connect

    Kiedrowski, Brian C; Solomon, Clell J

    2010-12-09

    Four tests are developed to assess the statistical reliability of distributional or mesh tallies. To this end, the relative variance density function is developed and its moments are studied using simplified, non-transport models. The statistical tests are performed upon the results of MCNP calculations of three different transport test problems and appear to show that the tests are appropriate indicators of global statistical quality.

  1. Impact of flow pulsatility on arterial drug distribution in stent-based therapy

    E-print Network

    O'Brien, Caroline C.

    Drug-eluting stents reside in a dynamic fluid environment where the extent to which drugs are distributed within the arterial wall is critically modulated by the blood flowing through the arterial lumen. Yet several factors ...

  2. 77 FR 59156 - Antimicrobial Animal Drug Sales and Distribution Reporting; Extension of Comment Period

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-26

    ...DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 514 [Docket No. FDA-2012-N-0447] Antimicrobial Animal Drug Sales and Distribution Reporting; Extension of Comment...

  3. Mapping Drug Distribution in Brain Tissue Using Liquid Extraction Surface Analysis Mass Spectrometry Imaging.

    PubMed

    Swales, John G; Tucker, James W; Spreadborough, Michael J; Iverson, Suzanne L; Clench, Malcolm R; Webborn, Peter J H; Goodwin, Richard J A

    2015-10-01

    Liquid extraction surface analysis mass spectrometry (LESA-MS) is a surface sampling technique that incorporates liquid extraction from the surface of tissue sections with nanoelectrospray mass spectrometry. Traditional tissue analysis techniques usually require homogenization of the sample prior to analysis via high-performance liquid chromatography mass spectrometry (HPLC-MS), but an intrinsic weakness of this is a loss of all spatial information and the inability of the technique to distinguish between actual tissue penetration and response caused by residual blood contamination. LESA-MS, in contrast, has the ability to spatially resolve drug distributions and has historically been used to profile discrete spots on the surface of tissue sections. Here, we use the technique as a mass spectrometry imaging (MSI) tool, extracting points at 1 mm spatial resolution across tissue sections to build an image of xenobiotic and endogenous compound distribution to assess drug blood-brain barrier penetration into brain tissue. A selection of penetrant and "nonpenetrant" drugs were dosed to rats via oral and intravenous administration. Whole brains were snap-frozen at necropsy and were subsequently sectioned prior to analysis by matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and LESA-MSI. MALDI-MSI, as expected, was shown to effectively map the distribution of brain penetrative compounds but lacked sufficient sensitivity when compounds were marginally penetrative. LESA-MSI was used to effectively map the distribution of these poorly penetrative compounds, highlighting its value as a complementary technique to MALDI-MSI. The technique also showed benefits when compared to traditional homogenization, particularly for drugs that were considered nonpenetrant by homogenization but were shown to have a measurable penetration using LESA-MSI. PMID:26350423

  4. IVAN: intelligent van for the distribution of pharmaceutical drugs.

    PubMed

    Moreno, Asier; Angulo, Ignacio; Perallos, Asier; Landaluce, Hugo; García Zuazola, Ignacio Julio; Azpilicueta, Leire; Astrain, José Javier; Falcone, Francisco; Villadangos, Jesús

    2012-01-01

    This paper describes a telematic system based on an intelligent van which is capable of tracing pharmaceutical drugs over delivery routes from a warehouse to pharmacies, without altering carriers' daily conventional tasks. The intelligent van understands its environment, taking into account its location, the assets and the predefined delivery route; with the capability of reporting incidences to carriers in case of failure according to the established distribution plan. It is a non-intrusive solution which represents a successful experience of using smart environments and an optimized Radio Frequency Identification (RFID) embedded system in a viable way to resolve a real industrial need in the pharmaceutical industry. The combination of deterministic modeling of the indoor vehicle, the implementation of an ad-hoc radiating element and an agile software platform within an overall system architecture leads to a competitive, flexible and scalable solution. PMID:22778659

  5. IVAN: Intelligent Van for the Distribution of Pharmaceutical Drugs

    PubMed Central

    Moreno, Asier; Angulo, Ignacio; Perallos, Asier; Landaluce, Hugo; Zuazola, Ignacio Julio García; Azpilicueta, Leire; Astrain, José Javier; Falcone, Francisco; Villadangos, Jesús

    2012-01-01

    This paper describes a telematic system based on an intelligent van which is capable of tracing pharmaceutical drugs over delivery routes from a warehouse to pharmacies, without altering carriers' daily conventional tasks. The intelligent van understands its environment, taking into account its location, the assets and the predefined delivery route; with the capability of reporting incidences to carriers in case of failure according to the established distribution plan. It is a non-intrusive solution which represents a successful experience of using smart environments and an optimized Radio Frequency Identification (RFID) embedded system in a viable way to resolve a real industrial need in the pharmaceutical industry. The combination of deterministic modeling of the indoor vehicle, the implementation of an ad-hoc radiating element and an agile software platform within an overall system architecture leads to a competitive, flexible and scalable solution. PMID:22778659

  6. Numerical simulation on the effects of drug eluting stents at different Reynolds numbers on hemodynamic and drug concentration distribution

    PubMed Central

    2015-01-01

    Background The changes of hemodynamics and drug concentration distribution caused by the implantation of drug eluting stents (DESs) in curved vessels have significant effects on In-Stent Restenosis. Methods A 3D virtual stent with 90°curvature was modelled and the distribution of wall shear stress (WSS) and drug concentration in this model were numerically studied at Reynolds numbers of 200, 400, 600, 800. Results The results showed that (1) the intensity of secondary flow at the 45° cross-section was stronger than that at the 90° cross-section; (2) As the Reynolds number increases, the WSS decreases. When the Reynolds number reaches 600, the low-WSS region only accounts for 3% of the total area. (3) The effects of Reynolds number on drug concentration in the vascular wall decreases in proportionally and then the blood velocity increased 4 times, the drug concentration in the vascular wall decreased by about 30%. (4) The size of the high drug concentration region is inversely proportional to the Reynolds number. As the blood velocity increases, the drug concentration in the DES decreases, especially at the outer bend. Conclusions It is beneficial for the patient to decrease vigorous activities and keep calm at the beginning of the stent implantation, because a substantial amount of the drug is released in the first two months of stent implantation, thus a calm status is conducive to drug release and absorption; Subsequently, appropriate exercise which increases the blood velocity is helpful in decreasing regions of low-WSS. PMID:25602685

  7. 7 CFR 1230.72 - Distribution of assessments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Distribution of assessments. 1230.72 Section 1230.72 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... § 1230.72 Distribution of assessments. Assessments remitted to the Board shall be distributed as...

  8. 7 CFR 1230.72 - Distribution of assessments.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Distribution of assessments. 1230.72 Section 1230.72 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... § 1230.72 Distribution of assessments. Assessments remitted to the Board shall be distributed as...

  9. Understanding pharmacokinetics using realistic computational models of fluid dynamics: biosimulation of drug distribution within the CSF space for intrathecal drugs.

    PubMed

    Kuttler, Andreas; Dimke, Thomas; Kern, Steven; Helmlinger, Gabriel; Stanski, Donald; Finelli, Luca A

    2010-12-01

    We introduce how biophysical modeling in pharmaceutical research and development, combining physiological observations at the tissue, organ and system level with selected drug physiochemical properties, may contribute to a greater and non-intuitive understanding of drug pharmacokinetics and therapeutic design. Based on rich first-principle knowledge combined with experimental data at both conception and calibration stages, and leveraging our insights on disease processes and drug pharmacology, biophysical modeling may provide a novel and unique opportunity to interactively characterize detailed drug transport, distribution, and subsequent therapeutic effects. This innovative approach is exemplified through a three-dimensional (3D) computational fluid dynamics model of the spinal canal motivated by questions arising during pharmaceutical development of one molecular therapy for spinal cord injury. The model was based on actual geometry reconstructed from magnetic resonance imaging data subsequently transformed in a parametric 3D geometry and a corresponding finite-volume representation. With dynamics controlled by transient Navier-Stokes equations, the model was implemented in a commercial multi-physics software environment established in the automotive and aerospace industries. While predictions were performed in silico, the underlying biophysical models relied on multiple sources of experimental data and knowledge from scientific literature. The results have provided insights into the primary factors that can influence the intrathecal distribution of drug after lumbar administration. This example illustrates how the approach connects the causal chain underlying drug distribution, starting with the technical aspect of drug delivery systems, through physiology-driven drug transport, then eventually linking to tissue penetration, binding, residence, and ultimately clearance. Currently supporting our drug development projects with an improved understanding of systems physiology, biophysical models are being increasingly used to characterize drug transport and distribution in human tissues where pharmacokinetic measurements are difficult or impossible to perform. Importantly, biophysical models can describe emergent properties of a system, i.e. properties not identifiable through the study of the system's components taken in isolation. PMID:21132572

  10. The Development of a Test to Assess Drug Using Behavior.

    ERIC Educational Resources Information Center

    Althoff, Michael E.

    The objective of the study was to develop a test which could measure both the qualitative and quantitative aspects of drug-using behavior, including such factors as attitudes toward drugs, experience with drugs, and knowledge about drugs. The Drug Use Scale was developed containing 134 items and dealing with five classes of drugs: marijuana,…

  11. Distributed Drug Discovery: Advancing Chemical Education through Contextualized Combinatorial Solid-Phase Organic Laboratories

    ERIC Educational Resources Information Center

    Scott, William L.; Denton, Ryan E.; Marrs, Kathleen A.; Durrant, Jacob D.; Samaritoni, J. Geno; Abraham, Milata M.; Brown, Stephen P.; Carnahan, Jon M.; Fischer, Lindsey G.; Glos, Courtney E.; Sempsrott, Peter J.; O'Donnell, Martin J.

    2015-01-01

    The Distributed Drug Discovery (D3) program trains students in three drug discovery disciplines (synthesis, computational analysis, and biological screening) while addressing the important challenge of discovering drug leads for neglected diseases. This article focuses on implementation of the synthesis component in the second-semester…

  12. 78 FR 59308 - Antimicrobial Animal Drug Sales and Distribution Annual Summary Report Data Tables

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-26

    ... distribution data collected from sponsors of antimicrobial new animal drugs in accordance with the new animal... new animal drug applications to establish and maintain records and make such reports to FDA of data and other information relating to experience with their new animal drugs as required by regulation...

  13. A Drug Education Needs Assessment in a Rural Elementary School System: Results and Curriculum Recommendations.

    ERIC Educational Resources Information Center

    Sarvela, Paul D.; And Others

    This report presents the results of a needs assessment study on comprehensive drug education conducted for a small rural K-8 school. A brief review examines the literature on drug and alcohol abuse among rural youth. Parents, teachers, and students were surveyed to assess their needs, interests, and knowledge of drug and alcohol abuse. Twenty…

  14. Estimation of Drug Binding to Brain Tissue: Methodology and in Vivo Application of a Distribution Assay in Brain Polar Lipids.

    PubMed

    Belli, Sara; Assmus, Frauke; Wagner, Bjoern; Honer, Michael; Fischer, Holger; Schuler, Franz; Alvarez-Sánchez, Rubén

    2015-12-01

    The unbound drug concentration-effect relationship in brain is a key aspect in CNS drug discovery and development. In this work, we describe an in vitro high-throughput distribution assay between an aqueous buffer and a microemulsion of porcine brain polar lipids (BPL). The derived distribution coefficient LogDBPL was applied to the prediction of unbound drug concentrations in brain (Cu,b) and nonspecific binding to brain tissue. The in vivo relevance of the new assay was assessed for a large set of proprietary drug candidates and CNS drugs by (1) comparing observed compound concentrations in rat CSF with Cu,b calculated using the LogDBPL assay in combination with total drug brain concentrations, (2) comparing Cu,b derived from LogDBPL and total drug brain concentrations to Cu,b estimated using in vitro P-glycoprotein efflux ratio data and unbound drug plasma levels, and (3) comparing tissue nonspecific binding data from human brain autoradiography studies for 17 PET tracer candidates to distribution in BPL. In summary, the LogDBPL assay provides a predicted drug fraction unbound in brain tissue that is nearly identical to brain homogenate equilibrium dialysis with an estimation of in vivo Cu,b that is superior to LogD in octanol. LogDBPL complements the approach for predicting Cu,b based on in vitro P-glycoprotein efflux ratio and in vivo unbound plasma concentration and stands as a fast and cost-effective tool for nonspecific brain binding optimization of PET ligand candidates. PMID:26560069

  15. 22 CFR 1008.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 2 2014-04-01 2014-04-01 false To whom must I distribute my drug-free workplace statement? 1008.210 Section 1008.210 Foreign Relations INTER-AMERICAN FOUNDATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements for Recipients Other Than Individuals § 1008.210 To whom must I distribute...

  16. 34 CFR 84.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 1 2012-07-01 2012-07-01 false To whom must I distribute my drug-free workplace statement? 84.210 Section 84.210 Education Office of the Secretary, Department of Education GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements for Recipients Other Than Individuals § 84.210 To whom must I distribute...

  17. 22 CFR 312.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 2 2014-04-01 2014-04-01 false To whom must I distribute my drug-free workplace statement? 312.210 Section 312.210 Foreign Relations PEACE CORPS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements for Recipients Other Than Individuals § 312.210 To whom must I distribute my...

  18. 28 CFR 83.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false To whom must I distribute my drug-free workplace statement? 83.210 Section 83.210 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) GOVERNMENT-WIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (GRANTS) Requirements for Recipients Other Than Individuals § 83.210 To whom must I distribute...

  19. 22 CFR 1008.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 2 2011-04-01 2009-04-01 true To whom must I distribute my drug-free workplace statement? 1008.210 Section 1008.210 Foreign Relations INTER-AMERICAN FOUNDATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements for Recipients Other Than Individuals § 1008.210 To whom must I distribute...

  20. Examining the spatial distribution of law enforcement encounters among people who inject drugs after implementation of Mexico's drug policy reform.

    PubMed

    Gaines, Tommi L; Beletsky, Leo; Arredondo, Jaime; Werb, Daniel; Rangel, Gudelia; Vera, Alicia; Brouwer, Kimberly

    2015-04-01

    In 2009, Mexico decriminalized the possession of small amounts of illicit drugs for personal use in order to refocus law enforcement resources on drug dealers and traffickers. This study examines the spatial distribution of law enforcement encounters reported by people who inject drugs (PWID) in Tijuana, Mexico to identify concentrated areas of policing activity after implementation of the new drug policy. Mapping the physical location of law enforcement encounters provided by PWID (n?=?461) recruited through targeted sampling, we identified hotspots of extra-judicial encounters (e.g., physical/sexual abuse, syringe confiscation, and money extortion by law enforcement) and routine authorized encounters (e.g., being arrested or stopped but not arrested) using point density maps and the Getis-Ord Gi* statistic calculated at the neighborhood-level. Approximately half of the participants encountered law enforcement more than once in a calendar year and nearly one third of these encounters did not result in arrest but involved harassment or abuse by law enforcement. Statistically significant hotspots of law enforcement encounters were identified in a limited number of neighborhoods located in areas with known drug markets. At the local-level, law enforcement activities continue to target drug users despite a national drug policy that emphasizes drug treatment diversion rather than punitive enforcement. There is a need for law enforcement training and improved monitoring of policing tactics to better align policing with public health goals. PMID:25300503

  1. Spatial distribution and characteristics of injecting drug users (IDU) in five Northeastern states of India

    PubMed Central

    2011-01-01

    Background Injecting drugs is the major driving force of human immunodeficiency virus (HIV) epidemic in Northeastern India. We have assessed the spatial distribution of locations where injecting drug users (IDU) congregate, as well as the risk behaviour and key characteristics of IDUs to develop new strategies strengthening intervention measures for HIV prevention in this region. Methods Locations of IDUs congregation for buying and injecting drugs were identified through Key Informants (KI). Verification of the location and its characteristics were confirmed through field visits. We also conducted semi-structured and structured interviews with IDUs to learn more about their injecting behaviour and other characteristics. Results Altogether, 2462 IDU locations were identified in 5 states. The number of IDU locations was found to be greater in the states bordering Myanmar. Private houses, parks, abandoned buildings, pharmacies, graveyards, and isolated places were the most frequently chosen place for injecting drugs. Many injecting locations were visited by IDUs of varying ages, of which about 10-20% of locations were for females. In some locations, female IDUs were also involved in sex work. Sharing of needle and syringes was reported in all the states by large proportion of IDUs, mainly with close friends. However, even sharing with strangers was not uncommon. Needle and syringes were mainly procured from pharmacies, drug peddlers and friends. Lack of access to free sterile needles and syringes, and inconsistent supplies from intervention programs, were often given as the cause of sharing or re-use of needles and syringes by IDUs. Most of the IDUs described a negative attitude of the community towards them. Conclusion We highlight the injection of drugs as a problem in 5 Northeastern India states where this is the major driving force of an HIV epidemic. Also highlighted are the large numbers of females that are unrecognized as IDUs and the association between drug use and sex work. Understanding of risk behaviours and other key charecteristics of IDUs in the region will help in strengthening harm reduction efforts that can prevent HIV transmission. PMID:21281465

  2. Reducing attrition in drug development: smart loading preclinical safety assessment.

    PubMed

    Roberts, Ruth A; Kavanagh, Stefan L; Mellor, Howard R; Pollard, Christopher E; Robinson, Sally; Platz, Stefan J

    2014-03-01

    Entry into the crucial preclinical good laboratory practice (GLP) stage of toxicology testing triggers significant R&D investment yet >20% of AstraZeneca's potential new medicines have been stopped for safety reasons in this GLP phase alone. How could we avoid at least some of these costly failures? An analysis of historical toxicities that caused stopping ('stopping toxicities') showed that >50% were attributable to target organ toxicities emerging within 2 weeks of repeat dosing or to acute cardiovascular risks. By frontloading 2-week repeat-dose toxicity studies and a comprehensive assessment of cardiovascular safety, we anticipate a potential 50% reduction in attrition in the GLP phase. This will reduce animal use overall, save significant R&D costs and improve drug pipeline quality. PMID:24269835

  3. Open drug scenes and drug-related public nuisance: a visual rapid assessment research study in Dublin, Ireland.

    PubMed

    Van Hout, Marie Claire; Bingham, Tim

    2013-01-01

    The research was undertaken at a time of increasing public concerns for drug- and alcohol-related public nuisance in the city center of Dublin, Ireland. Rapid Assessment Research was conducted involving qualitative interviewing with drug service users; business, transport, community, voluntary, and statutory stakeholders (n = 61); and an environmental mapping exercise. The interplay between homelessness, loitering, an influx of drug users via city metro systems, transient open drug scenes, street drinking, drug injecting, intimidation, knife crime, and prescribed medication abuse was evident. Potential strategies to address drug and alcohol related public nuisance are advised to include the relocation of treatment services, targeted harm reduction initiatives, urban regeneration, improved community rehabilitation pathways, and heightened policing intensity. PMID:23768432

  4. Impact of drug administration route on drug delivery and distribution into the lung: an imaging mass spectrometry approach.

    PubMed

    Zecchi, Riccardo; Trevisani, Marcello; Pittelli, Maria; Pedretti, Pamela; Manni, Maria Elena; Pieraccini, Giuseppe; Pioselli, Barbara; Amadei, Francesco; Moneti, Gloriano; Catinella, Silvia

    2013-01-01

    During the last decade, significant technological improvements in mass spectrometry have had a great impact on drug discovery. The development of matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) has set a new frontier for the study of the distribution of endogenous and exogenous molecules present within a tissue. MALDI-IMS is a surface sampling technique that allows not only the detection of multiple analytes but also gives the spatial distribution of those analytes. Active compounds for pulmonary disease need an optimal and well-studied delivery into the lungs, in order to assure distribution with greater penetration into the peripheral or the alveolar region of the lung to maximize the therapeutic effects. IMS is very useful in the field of drug discovery, showing drug delivery and distribution in the body and organs. In this study, we present a comparison between two different ways of carrying out pulmonary drug administration: inhalation of a nebulized aerosol of aqueous drug solutions and intratracheal administration, which is much simpler, not expensive and commonly used during in vivo screening. Tiotropium bromide is a long-acting anticholinergic medicine used for maintenance treatment of chronic obstructive pulmonary disease. In the present work, tiotropium was administered by nebulization and by intratracheal instillation to guinea pigs at doses able to induce significant anti-bronchoconstrictive activity. Lung samples were dissected, frozen, cryosectioned and coated with matrix (?-hydroxy-cinnamic acid). IMS analyses were performed using a MALDI-LTQ-Orbitrap XL. Using this technique we were able to compare different distributions of the drug depending on the method of administration. PMID:24378465

  5. A Rational Probabilistic Method for Spatially Distributed Landslide Hazard Assessment

    E-print Network

    Haneberg, William C.

    A Rational Probabilistic Method for Spatially Distributed Landslide Hazard Assessment WILLIAM C, Landslides, Probabi- listic, Computer Applications, West Virginia ABSTRACT First-order, second-moment (FOSM models to perform spatially distributed probabilistic landslide hazard analyses. This is most easily

  6. Serotype Distribution and Drug Resistance in Streptococcus pneumoniae, Palestinian Territories

    PubMed Central

    Kattan, Randa; Abu Rayyan, Amal; Zheiman, Inas; Idkeidek, Suzan; Baraghithi, Sabri; Rishmawi, Nabeel; Turkuman, Sultan; Abu-Diab, Afaf; Ghneim, Riyad; Zoughbi, Madeleine; Dauodi, Rula; Ghneim, Raed; Issa, Abed-El-Razeq; Siryani, Issa; Al Qas, Randa; Liddawi, Rawan; Khamash, Hatem; Kanaan, Moein; Marzouqa, Hiyam

    2011-01-01

    To determine antimicrobial drug resistance of Streptococcus pneumoniae serotypes, we analyzed isolates from blood cultures of sick children residing in the West Bank before initiation of pneumococcal vaccination. Of 120 serotypes isolated, 50.8%, 73.3%, and 80.8% of the bacteremia cases could have been prevented by pneumococcal conjugate vaccines. Serotype 14 was the most drug-resistant serotype isolated. PMID:21192863

  7. 10 CFR 607.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false To whom must I distribute my drug-free workplace statement? 607.210 Section 607.210 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements for Recipients Other Than...

  8. 45 CFR 630.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 3 2014-10-01 2014-10-01 false To whom must I distribute my drug-free workplace statement? 630.210 Section 630.210 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements for Recipients Other...

  9. 49 CFR 32.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false To whom must I distribute my drug-free workplace statement? 32.210 Section 32.210 Transportation Office of the Secretary of Transportation GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements for Recipients Other Than Individuals § 32.210 To whom must I...

  10. 13 CFR 147.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false To whom must I distribute my drug-free workplace statement? 147.210 Section 147.210 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (NONPROCUREMENT) Requirements for Recipients Other Than Individuals § 147.210 To...

  11. 29 CFR 1472.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 4 2011-07-01 2011-07-01 false To whom must I distribute my drug-free workplace statement? 1472.210 Section 1472.210 Labor Regulations Relating to Labor (Continued) FEDERAL MEDIATION AND CONCILIATION SERVICE GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements for Recipients Other Than Individuals §...

  12. 45 CFR 1155.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 3 2011-10-01 2011-10-01 false To whom must I distribute my drug-free workplace statement? 1155.210 Section 1155.210 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES NATIONAL ENDOWMENT FOR THE ARTS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE...

  13. 45 CFR 630.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 3 2011-10-01 2011-10-01 false To whom must I distribute my drug-free workplace statement? 630.210 Section 630.210 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements for Recipients Other...

  14. 31 CFR 20.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance: Treasury 1 2013-07-01 2013-07-01 false To whom must I distribute my drug-free workplace statement? 20.210 Section 20.210 Money and Finance: Treasury Office of the Secretary of the Treasury GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements for Recipients Other Than Individuals § 20.210...

  15. 29 CFR 1472.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 4 2014-07-01 2014-07-01 false To whom must I distribute my drug-free workplace statement? 1472.210 Section 1472.210 Labor Regulations Relating to Labor (Continued) FEDERAL MEDIATION AND CONCILIATION SERVICE GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements for Recipients Other Than Individuals §...

  16. 22 CFR 1509.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 2 2014-04-01 2014-04-01 false To whom must I distribute my drug-free workplace statement? 1509.210 Section 1509.210 Foreign Relations AFRICAN DEVELOPMENT FOUNDATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements for Recipients Other Than Individuals § 1509.210 To whom must I...

  17. 32 CFR 26.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 1 2013-07-01 2013-07-01 false To whom must I distribute my drug-free workplace statement? 26.210 Section 26.210 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements for...

  18. 13 CFR 147.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false To whom must I distribute my drug-free workplace statement? 147.210 Section 147.210 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (NONPROCUREMENT) Requirements for Recipients Other Than Individuals § 147.210 To...

  19. 45 CFR 1155.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 3 2014-10-01 2014-10-01 false To whom must I distribute my drug-free workplace statement? 1155.210 Section 1155.210 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES NATIONAL ENDOWMENT FOR THE ARTS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE...

  20. 36 CFR 1212.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false To whom must I distribute my drug-free workplace statement? 1212.210 Section 1212.210 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION GENERAL RULES GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements...

  1. 36 CFR 1212.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false To whom must I distribute my drug-free workplace statement? 1212.210 Section 1212.210 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION GENERAL RULES GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements...

  2. A less irritant norcantharidin lipid microspheres: formulation and drug distribution.

    PubMed

    Lixin, Wang; Haibing, He; Xing, Tang; Ruiying, Shao; Dawei, Chen

    2006-10-12

    Lipid microspheres (LM) have recently been used as intravenous (i.v.) carriers for drugs, which are sufficiently soluble in oil. However, in the case of norcantharidin (NCTD), which is poorly soluble in both the water and oil phases, this approach is not feasible. In this study, NCTD-loaded LM was prepared by transferring the drug to the interfacial surface of the oil and aqueous phases to produce a less irritating i.v. formulation of NCTD. A probe type sonicator was used to disperse NCTD into the oil phase together with lecithin and Tween 80. A high-pressure homogenization process was used to prepare the lipid microspheres and localize the drug at the surfactant layer. The LM loaded with NCTD consisted of 0.02% drug. Characterization of LMs and short-term stability was performed by photon correlation spectroscopy (PCS) and a centrifugation test was also carried out. The results showed that NCTD-loaded LM (2 mg/ml) with over 80% NCTD loaded in the interfacial surface were stable for a period of 2 months, and were suitable for i.v. injection in terms of size and stability, whether be diluted or not. Such formulations produced less pain and irritation in animal studies. PMID:16828998

  3. Intracellular distribution of psychotropic drugs in the grey and white matter of the brain: the role of lysosomal trapping

    PubMed Central

    Daniel, W?adys?awa A; Wójcikowski, Jacek; Pa?ucha, Agnieszka

    2001-01-01

    Since the brain is not a homogenous organ (i.e. the phospholipid pattern and density of lysosomes may vary in its different regions), in the present study we examined the uptake of psychotropic drugs by vertically cut slices of whole brain, grey (cerebral cortex) and white (corpus callosum, internal capsule) matter of the brain and by neuronal and astroglial cell cultures.Moreover, we assessed the contribution of lysosomal trapping to total drug uptake (total uptake=lysosomal trapping+phospholipid binding) by tissue slices or cells conducting experiments in the presence and absence of ‘lysosomal inhibitors', i.e., the lysosomotropic compound ammonium chloride (20?mM) or the Na+/H+-ionophore monensin (10??M), which elevated the internal pH of lysosomes. The initial concentration of psychotropic drug in the incubation medium was 5??M.Both total uptake and lysosomal trapping of the antidepressants investigated (imipramine, amitriptyline, fluoxetine, sertraline) and neuroleptics (promazine, perazine, thioridazine) were higher in the grey matter and neurones than in the white matter and astrocytes, respectively. Lysosomal trapping of the psychotropics occurred mainly in neurones where thioridazine sertraline and perazine showed the highest degree of lysosomotropism.Distribution interactions between antidepressants and neuroleptics took place in neurones via mutual inhibition of lysosomal trapping of drugs.A differential number of neuronal and glial cells in the brain may mask the lysosomal trapping and the distribution interactions of less potent lysosomotropic drugs in vertically cut brain slices.A reduction (via a distribution interaction) in the concentration of psychotropics in lysosomes (depot), which leads to an increase in their level in membranes and tissue fluids, may intensify the pharmacological action of the combined drugs. PMID:11606321

  4. Drugs for rare diseases: mixed assessment in Europe.

    PubMed

    2007-02-01

    (1) Worldwide, there are an estimated 6000 to 7000 rare diseases. Patients face special difficulties in obtaining an accurate diagnosis, adequate information about the disease, and access to qualified specialists. (2) Drug companies do not spontaneously conduct research on drugs for rare diseases, mainly because of the limited market for each indication. Only a few dozen of these drugs were available in France before 2000. (3) In 2000 the European Union adopted a Regulation, based on experience in the United States, aimed at promoting the development of drugs for patients suffering from rare diseases, i.e. 'orphan drugs'. (4) In Europe, orphan drug status can be granted when the prevalence of the disease does not exceed 5 cases per 10 000 inhabitants (or when it is more frequent but profitability is likely to be inadequate). (5) Companies that market an orphan drug receive a variety of financial assistance as well as a 10-year marketing monopoly. (6) Between April 2000 and April 2005, 268 medicinal products received European orphan drug status and 22 were granted European marketing authorization. (7) Access to these drugs varies greatly from one European Union Member State to another, mainly because of the high annual treatment costs (up to 300 000 euros per patient). Worldwide sales of the orphan drug imatinib reached more than two thousand million dollars in 2005. (8) Our systematic analyses (see the New Products column of our French edition la revue Prescrire) show that only 5 drugs which received European orphan drug status before May 2005 were for diseases for which there had previously been no treatment. (9) Clinical evaluation of orphan drugs is hindered by the small number of patients available for clinical trials. Some orphan drugs are adequately tested before being brought to market. Others are not compared to existing treatments. In many cases, surrogate criteria are used instead of clinical endpoints. These methodological flaws are in no way limited to orphan drugs. (10) Not all orphan drugs represent therapeutic advances. Clinical research and evaluation should continue after marketing authorization has been granted. (11) More drugs, with better-documented efficacy and safety, are now available for patients who previously had no effective treatment options. Yet there is too much duplication and too little evaluation, and too many drugs are extremely expensive, meaning that patients in many European countries cannot benefit. And many rare diseases are still neglected. PMID:17323539

  5. High Concentrations of Drug in Target Tissues Following Local Controlled Release Are Utilized for Both Drug Distribution and Biologic Effect: An Example with Epicardial Inotropic Drug Delivery

    PubMed Central

    Maslov, Mikhail Y.; Edelman, Elazer R.; Wei, Abraham E.; Pezone, Matthew J.; Lovich, Mark A.

    2015-01-01

    Local drug delivery preferentially loads target tissues with a concentration gradient from the surface or point of release that tapers down to more distant sites. Drug that diffuses down this gradient must be in unbound form, but such drug can only elicit a biologic effect through receptor interactions. Drug excess loads tissues, increasing gradients and driving penetration, but with limited added biological response. We examined the hypothesis that local application reduces dramatically systemic circulating drug levels but leads to significantly higher tissue drug concentration than might be needed with systemic infusion in a rat model of local epicardial inotropic therapy. Epinephrine was infused systemically or released locally to the anterior wall of the heart using a novel polymeric platform that provides steady, sustained release over a range of precise doses. Epinephrine tissue concentration, upregulation of cAMP, and global left ventricular response were measured at equivalent doses and at doses equally effective in raising indices of contractility. The contractile stimulation by epinephrine was linked to drug tissue levels and commensurate cAMP upregulation for IV systemic infusion, but not with local epicardial delivery. Though cAMP was a powerful predictor of contractility with local application, tissue epinephrine levels were high and variable - only a small fraction of the deposited epinephrine was utilized in second messenger signaling and biologic effect. The remainder of deposited drug was likely used in diffusive transport and distribution. Systemic side effects were far more profound with IV infusion which, though it increased contractility, also induced tachycardia and loss of systemic vascular resistance, which were not seen with local application. Local epicardial inotropic delivery illustrates then a paradigm of how target tissues differentially handle and utilize drug compared to systemic infusion. PMID:23872515

  6. Anticancer efficacy and absorption, distribution, metabolism, and toxicity studies of Aspergiolide A in early drug development

    PubMed Central

    Wang, Yuanyuan; Qi, Xin; Li, Dehai; Zhu, Tianjiao; Mo, Xiaomei; Li, Jing

    2014-01-01

    Since the first anthracycline was discovered, many other related compounds have been studied in order to overcome its defects and improve efficacy. In the present paper, we investigated the anticancer effects of a new anthracycline, aspergiolide A (ASP-A), from a marine-derived fungus in vitro and in vivo, and we evaluated the absorption, distribution, metabolism, and toxicity drug properties in early drug development. We found that ASP-A had activity against topoisomerase II that was comparable to adriamycin. ASP-A decreased the growth of various human cancer cells in vitro and induced apoptosis in BEL-7402 cells via a caspase-dependent pathway. The anticancer efficacy of ASP-A on the growth of hepatocellular carcinoma xenografts was further assessed in vivo. Results showed that, compared with the vehicle group, ASP-A exhibited significant anticancer activity with less loss of body weight. A pharmacokinetics and tissue distribution study revealed that ASP-A was rapidly cleared in a first order reaction kinetics manner, and was enriched in cancer tissue. The maximal tolerable dose (MTD) of ASP-A was more than 400 mg/kg, and ASP-A was not considered to be potentially genotoxic or cardiotoxic, as no significant increase of micronucleus rates or inhibition of the hERG channel was seen. Finally, an uptake and transport assay of ASP-A was performed in monolayers of Caco-2 cells, and ASP-A was shown to be absorbed through the active transport pathway. Altogether, these results indicate that ASP-A has anticancer activity targeting topoisomerase II, with a similar structure and mechanism to adriamycin, but with much lower toxicity. Nonetheless, further molecular structure optimization is necessary. PMID:25378909

  7. Methodological Issues in Assessing the Impact of Prenatal Drug Exposure

    PubMed Central

    Konijnenberg, Carolien

    2015-01-01

    Prenatal drug exposure is a common public health concern that can result in perinatal complications, birth defects, and developmental disorders. The growing literature regarding the effects of prenatal exposure to specific drugs such as tobacco, alcohol, cocaine, and heroin is often conflicting and constantly changing. This review discusses several reasons why the effects of prenatal drug exposure are so difficult to determine, including variations in dose, timing, duration of exposure, polydrug use, unreliable measures of drug exposure, latent or “sleeper” effects, genetic factors, and socioenvironmental influences. In addition to providing research guidelines, this review also aims to help clinicians and policy makers to identify the strengths and weaknesses in studies investigating the effects of prenatal drug exposure. This knowledge may be used to make better informed decisions regarding the appropriate treatment for pregnant, drug-dependent women and their children. PMID:26604776

  8. Health technology assessment in the Balkans: opportunities for a balanced drug assessment system

    PubMed Central

    Dankó, Dávid; Petrova, Guenka

    2014-01-01

    Countries in the Balkan region use pharmaco-economic data for decisions about the inclusion of new pharmaceuticals into their positive drug lists, but no predefined frameworks are used and resources for health technology assessment (HTA) are limited. The goal of this analysis is to investigate into possible development directions for the HTA system in the region, and provide some practical recommendations for a sustainable model. For this purpose, the main factors currently influencing HTA in Balkan countries are briefly presented, and possible development strategies are compared. A resource-saving balanced assessment approach is proposed. It is aligned with available resources and capabilities, and helps access to new pharmaceuticals while ensuring the transparency of decision-making processes and the stability of the pharmaceutical budget. PMID:26019605

  9. Comparison of self-reported drug use with quantitative and qualitative urinalysis for assessment of drug use in treatment studies.

    PubMed

    Preston, K L; Silverman, K; Schuster, C R; Cone, E J

    1997-01-01

    The effectiveness of substance abuse treatment programs can be monitored by self-reported drug use and objectively measured by qualitative and quantitative urinalysis. The advantages and disadvantages of each of these three methods of assessing drug use are reviewed. Data collected in a clinical trial of a behavioral treatment for cocaine abuse are used to evaluate the relationships among qualitative and quantitative urinalysis for cocaine metabolite and self-reported cocaine use. Qualitative and quantitative urine testing showed greater rates of drug use than that shown by self-report, though there were significant correlations between self-reported use and urine toxicology results. Benzoylecgonine concentrations in urine specimens supported the suggestions that rates of drug use as determined by qualitative urinalysis are artificially high due to carryover and were informative about subjects' patterns of use. PMID:9243560

  10. 21 CFR 809.40 - Restrictions on the sale, distribution, and use of OTC test sample collection systems for drugs...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Restrictions on the sale, distribution, and use of OTC test sample collection systems for drugs of abuse testing. 809.40 Section 809.40 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IN VITRO DIAGNOSTIC PRODUCTS FOR HUMAN...

  11. 21 CFR 212.90 - What actions must I take to control the distribution of PET drug products?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    21 Food and Drugs 4 2014-04-01 2014-04-01 false What actions must I take to control the distribution of PET drug products? 212.90 Section 212.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

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

    PubMed

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

    2015-11-30

    Health Technology Assessment (HTA) is a multidisciplinary health political instrument that evaluates the consequences, mainly clinical and economical, of a health care technology; the HTA aim is to produce and spread information on scientific and technological innovation for health political decision making process. Drug delivery systems (DDS), such as nanocarriers, are technologically complex but they have pivotal relevance in therapeutic innovation. The HTA process, as commonly applied to conventional drug evaluation, should upgrade to a full pharmaceutical assessment, considering the DDS complexity. This is useful to study more in depth the clinical outcome and to broaden its critical assessment toward pharmaceutical issues affecting the patient and not measured by the current clinical evidence approach. We draw out the expertise necessary to perform the pharmaceutical assessment and we propose a format to evaluate the DDS technological topics such as formulation and mechanism of action, physicochemical characteristics, manufacturing process. We integrated the above-mentioned three points in the Evidence Based Medicine approach, which is data source for any HTA process. In this regard, the introduction of a Pharmaceutics Expert figure in the HTA could be fundamental to grant a more detailed evaluation of medicine product characteristics and performances and to help optimizing DDS features to overcome R&D drawbacks. Some aspects of product development, such as manufacturing processes, should be part of the HTA as innovative manufacturing processes allow new products to reach more effectively patient bedside. HTA so upgraded may encourage resource allocating payers to invest in innovative technologies and providers to focus on innovative material properties and manufacturing processes, thus contributing to bring more medicines in therapy in a sustainable manner. PMID:26399633

  13. Assessment of AIDS Risk among Treatment Seeking Drug Abusers.

    ERIC Educational Resources Information Center

    Black, John L.; And Others

    Intravenous (IV) drug abusers are at risk for contracting transmittable diseases such as acquired immunodeficiency syndrome (AIDS) and hepatitis B. This study was conducted to investigate the prevalence of risk behaviors for acquiring and transmitting AIDS and hepatitis B among treatment-seeking drug abusers (N=168). Subjects participated in a…

  14. Effect of heterogeneous microvasculature distribution on drug delivery to solid tumour

    NASA Astrophysics Data System (ADS)

    Zhan, Wenbo; Gedroyc, Wladyslaw; Xu, Xiao Yun

    2014-11-01

    Most of the computational models of drug transport in vascular tumours assume a uniform distribution of blood vessels through which anti-cancer drugs are delivered. However, it is well known that solid tumours are characterized by dilated microvasculature with non-uniform diameters and irregular branching patterns. In this study, the effect of heterogeneous vasculature on drug transport and uptake is investigated by means of mathematical modelling of the key physical and biochemical processes in drug delivery. An anatomically realistic tumour model accounting for heterogeneous distribution of blood vessels is reconstructed based on magnetic resonance images of a liver tumour. Numerical simulations are performed for different drug delivery modes, including direct continuous infusion and thermosensitive liposome-mediated delivery, and the anti-cancer effectiveness is evaluated through changes in tumour cell density based on predicted intracellular concentrations. Comparisons are made between regions of different vascular density, and between the two drug delivery modes. Our numerical results show that both extra- and intra-cellular concentrations in the liver tumour are non-uniform owing to the heterogeneous distribution of tumour vasculature. Drugs accumulate faster in well-vascularized regions, where they are also cleared out more quickly, resulting in less effective tumour cell killing in these regions. Compared with direct continuous infusion, the influence of heterogeneous vasculature on anti-cancer effectiveness is more pronounced for thermosensitive liposome-mediated delivery.

  15. Assessment of Drug-Drug Interactions between Daclatasvir and Methadone or Buprenorphine-Naloxone

    PubMed Central

    Wang, R.; Luo, W.-L.; Wastall, P.; Kandoussi, H.; DeMicco, M.; Bruce, R. D.; Hwang, C.; Bertz, R.; Bifano, M.

    2015-01-01

    Hepatitis C virus (HCV) infection is common among people who inject drugs, including those managed with maintenance opioids. Pharmacokinetic interactions between opioids and emerging oral HCV antivirals merit evaluation. Daclatasvir is a potent pangenotypic inhibitor of the HCV NS5A replication complex recently approved for HCV treatment in Europe and Japan in combination with other antivirals. The effect of steady-state daclatasvir (60 mg daily) on stable plasma exposure to oral opioids was assessed in non-HCV-infected subjects receiving methadone (40 to 120 mg; n = 14) or buprenorphine plus naloxone (8 to 24 mg plus 2 to 6 mg; n = 11). No relevant interaction was inferred if the 90% confidence interval (CI) of the geometric mean ratio (GMR) of opioid area under the plasma concentration-time curve over the dosing interval (AUC?) or maximum concentration in plasma (Cmax) with versus without daclatasvir was within literature-derived ranges of 0.7 to 1.43 (R- and S-methadone) or 0.5 to 2.0 (buprenorphine and norbuprenorphine). Dose-normalized AUC? for R-methadone (GMR, 1.08; 90% CI, 0.94 to 1.24), S-methadone (1.13; 0.99 to 1.30), and buprenorphine (GMR, 1.37; 90% CI, 1.24 to 1.52) were within the no-effect range. The norbuprenorphine AUC? was slightly elevated in the primary analysis (GMR, 1.62; 90% CI, 1.30 to 2.02) but within the no-effect range in a supplementary analysis of all evaluable subjects. Dose-normalized Cmax for both methadone enantiomers, buprenorphine and norbuprenorphine, were within the no-effect range. Standardized assessments of opioid pharmacodynamics were unchanged throughout daclatasvir administration with methadone or buprenorphine. Daclatasvir pharmacokinetics were similar to historical data. Coadministration of daclatasvir and opioids was generally well tolerated. In conclusion, these data suggest that daclatasvir can be administered with buprenorphine or methadone without dose adjustments. PMID:26124175

  16. Scientometric assessment of drugs for chronic pain, 1979–2013: rapid growth of publications, paucity of successful drugs

    PubMed Central

    Kissin, Igor

    2014-01-01

    The aim of this study was to find signs of progress in the pharmacotherapy of chronic pain over the past 35 years using scientometric analysis. The following scientometric indices were used: 1) popularity index, representing the share of articles on a specific drug(s) relative to all articles in the field of chronic pain; 2) index of change, representing the degree of growth in publications on a topic from one period to the next; 3) index of expectations, representing the ratio of the number of articles on a topic in the top 20 journals relative to the number of articles in all (>5,000) biomedical journals covered by PubMed; and 4) index of ultimate success, representing a publication outcome when a new drug takes the place of a common drug previously used for the same purpose. Publications on 55 drugs used in the treatment of chronic pain were assessed during seven 5-year periods, from 1979 to 2013. The rate of rise in the number of publications on chronic pain was exponential, with an increase of nearly ninefold from 2,346 articles over the 5-year period 1979–1983 to 21,095 articles in 2009–2013. However, despite this huge increase in publications, our scientometric analysis did not reveal signs of really successful drugs in this field. For the 2009–2013 period, the popularity index had a meaningful magnitude (from 0.5–2.8) for only 13 of 55 drugs. Five of them were opioids, including morphine, which had the highest index value of all drugs (2.8). None of the drugs had a high index of expectations in 2009–2013. The index of ultimate success was positive only with triptans in the relatively limited area of acute treatment of migraine. As a result, despite rapid growth in the number of publications, our scientometric analysis did not reveal signs of substantial progress in the field of pharmacotherapy for chronic pain. PMID:25187736

  17. Assessment of mechanical integrity for drug-eluting renal stent with micro-sized drug reservoirs.

    PubMed

    Hsiao, Hao-Ming; Chiu, Yi-Hsiang

    2013-01-01

    The drug-eluting stent (DES) has become the gold standard worldwide for the treatment of cardiovascular diseases. In recent years, an innovative variation of the DES with micro-sized drug reservoirs has been introduced. It allows programmable drug delivery with both spatial and temporal control and has several potential advantages over traditional DESs. However, creating such reservoirs on the stent struts may weaken the structure of the stent scaffolding and compromise its mechanical integrity. In this study, we propose to use this innovative stent concept in the renal indication for potential treatment of both renal artery stenosis (upstream) and its associated kidney diseases (downstream) at the same time. The effects of these micro-sized drug reservoirs on several key clinically relevant functional attributes of the drug-eluting renal stent were systematically and quantitatively investigated. Finite element models were developed to predict the mechanical integrity of a balloon-expandable stent at various stages. Results show that (1) creating drug reservoirs on a stent could impact the stent fatigue resistance to certain degrees; (2) drug reservoirs on the stent crowns lead to greater loss in all key stent attributes than reservoirs on either bar arms or connectors and (3) the proposed optimised depot stent was proven to be feasible and could triple drug capacity than the current DESs, with marginal trade-off in its key clinical attributes. These results can serve as the guidelines to help future stent designs to achieve the best combination of stent structural integrity and smart drug delivery in the future. PMID:22436070

  18. An informatics approach to assess pediatric pharmacotherapy: design and implementation of a hospital drug utilization system.

    PubMed

    Zuppa, Athena; Vijayakumar, Sundararajan; Jayaraman, Bhuvana; Patel, Dimple; Narayan, Mahesh; Vijayakumar, Kalpana; Mondick, John T; Barrett, Jeffrey S

    2007-09-01

    Drug utilization in the inpatient setting can provide a mechanism to assess drug prescribing trends, efficiency, and cost-effectiveness of hospital formularies and examine subpopulations for which prescribing habits may be different. Such data can be used to correlate trends with time-dependent or seasonal changes in clinical event rates or the introduction of new pharmaceuticals. It is now possible to provide a robust, dynamic analysis of drug utilization in a large pediatric inpatient setting through the creation of a Web-based hospital drug utilization system that retrieves source data from our accounting database. The production implementation provides a dynamic and historical account of drug utilization at the authors' institution. The existing application can easily be extended to accommodate a multi-institution environment. The creation of a national or even global drug utilization network would facilitate the examination of geographical and/or socioeconomic influences in drug utilization and prescribing practices in general. PMID:17656617

  19. Surveying Teens in School to Assess the Prevalence of Problematic Drug Use

    ERIC Educational Resources Information Center

    Falck, Russel S.; Nahhas, Ramzi W.; Li, Linna; Carlson, Robert G.

    2012-01-01

    Background: Illicit drug use by school-aged teens can adversely affect their health and academic achievement. This study used a survey administered in schools to assess the prevalence of problematic drug use among teenagers in a Midwestern community. Methods: Self-report data were collected from 11th- and 12th-grade students (N = 3974) in 16…

  20. A Choice Procedure to Assess the Aversive Effects of Drugs in Rodents

    ERIC Educational Resources Information Center

    Podlesnik, Christopher A.; Jimenez-Gomez, Corina; Woods, James H.

    2010-01-01

    The goal of this series of experiments was to develop an operant choice procedure to examine rapidly the punishing effects of intravenous drugs in rats. First, the cardiovascular effects of experimenter-administered intravenous histamine, a known aversive drug, were assessed to determine a biologically active dose range. Next, rats responded on…

  1. Assessing dietary intake of drug abusing Hispanic adults with and without HIV infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Drug abuse is an important risk factor for Human Immunodeficiency Virus (HIV) among Hispanics in the Northeastern United States and both drug abuse and HIV are associated with nutritional deficiencies. The selection of a dietary assessment method most appropriate for Hispanic adults with/without HIV...

  2. Assessment of Alcohol and Other Drug Use Behaviors in Health Professions Students

    ERIC Educational Resources Information Center

    Baldwin, Jeffrey N.; Scott, David M.; Agrawal, Sangeeta; Bartek, Jean K.; Davis-Hall, R. Ellen; Reardon, Thomas P.; DeSimone, Edward M., II

    2006-01-01

    Alcohol and other drug (AOD) use behaviors of health professions students (HPS) were assessed by surveying both university-based HPS and other nursing programs in a Midwestern state in 1999. Response was 2,646 (56.4%) of surveyed students. Family history of alcohol-related and drug-related problems were reported by 39.8% and 13.9%, respectively,…

  3. 78 FR 36787 - Rechanneling the Current Cardiac Risk Paradigm: Arrhythmia Risk Assessment During Drug...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-19

    ... From the Federal Register Online via the Government Printing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Rechanneling the Current Cardiac Risk Paradigm: Arrhythmia Risk... Cardiac Risk Paradigm: Arrhythmia Risk Assessment During Drug Development Without the Thorough QT...

  4. ADVANCED TOOLS FOR ASSESSING SELECTED PRESCRIPTION AND ILLICIT DRUGS IN TREATED SEWAGE EFFLUENTS AND SOURCE WATERS

    EPA Science Inventory

    The purpose of this poster is to present the application and assessment of advanced technologies in a real-world environment - wastewater effluent and source waters - for detecting six drugs (azithromycin, fluoxetine, omeprazole, levothyroxine, methamphetamine, and methylenedioxy...

  5. A study of the distribution of schistosomicidal drug H-3-7505 in mice

    SciTech Connect

    Hao, T.

    1985-05-01

    The authors have studied the distribution of H-3 labelled schistosomicidal drug in mice by autoradiography. The H-3-labelled substances were found in liver and kidney and in successfully decreasing amounts in brain, lung, heart, fat, testis, pancreas and spleen. In various cells the silver granules were present mainly in the cytoplasms but a few in the nucleus. After administration of this labelled schistosomicidal drug, the mice were killed and studied in groups successively at 4, 8, 24 hrs. No difference in the distribution of silver granules were observed. This fact indicated that, this drug was rapidly absorbed and highly concentrated with a long duration of reservation in liver. All of these favours the schistosomicidal effect of the drug. As this drug was highly concentrated in the cytoplasm of liver cells, that might provide a pathophysiologic basis for the explanation of jaundice in the clinical practice. Moreover, the appearance of toxic reaction in nervous system may be related to the relatively high concentration of the drug distributed in the brain.

  6. Risk Assessment of Drug Management Process in Women Surgery Department of Qaem Educational Hospital (QEH) Using HFMEA Method (2013)

    PubMed Central

    khani-Jazani, Reza; Molavi-Taleghani, Yasamin; Seyedin, Hesam; Vafaee-Najar, Ali; Ebrahimipour, Hossein; Pourtaleb, Arefeh

    2015-01-01

    Evaluation and improvement of drug management process are essential for patient safety. The present study was performed whit the aim of assessing risk of drug management process in Women Surgery Department of QEH using HFMEA method in 2013. A mixed method was used to analyze failure modes and their effects with HFMEA. To classify failure modes; nursing errors in clinical management model, for classifying factors affecting error; approved model by the UK National Health System, and for determining solutions for improvement; Theory of Inventive Problem Solving, were used. 48 failure modes were identified for 14 sub-process of five steps drug management process. The frequency of failure modes were as follow :35.3% in supplying step, 20.75% in prescription step, 10.4% in preparing step, 22.9% in distribution step and 10.35% in follow up and monitoring step. Seventeen failure modes (35.14%) were considered as non-acceptable risk (hazard score? 8) and were transferred to decision tree. Among 51 Influencing factors, the most common reasons for error were related to environmental factors (21.5%), and the less common reasons for error were related to patient factors (4.3%). HFMEA is a useful tool to evaluating, prioritization and analyzing failure modes in drug management process. Revision drug management process based focus-PDCA, assessing adverse drug reactions (ADR), USE patient identification bracelet, holding periodical pharmaceutical conferences to improve personnel knowledge, patient contribution in drug therapy; are performance solutions which were placed in work order. PMID:25901157

  7. How the Probability and Potential Clinical Significance of Pharmacokinetically Mediated Drug-Drug Interactions Are Assessed in Drug Development: Desvenlafaxine as an Example

    PubMed Central

    Nichols, Alice I.; Preskorn, Sheldon H.

    2015-01-01

    Objective: The avoidance of adverse drug-drug interactions (DDIs) is a high priority in terms of both the US Food and Drug Administration (FDA) and the individual prescriber. With this perspective in mind, this article illustrates the process for assessing the risk of a drug (example here being desvenlafaxine) causing or being the victim of DDIs, in accordance with FDA guidance. Data Sources/Study Selection: DDI studies for the serotonin-norepinephrine reuptake inhibitor desvenlafaxine conducted by the sponsor and published since 2009 are used as examples of the systematic way that the FDA requires drug developers to assess whether their new drug is either capable of causing clinically meaningful DDIs or being the victim of such DDIs. In total, 8 open-label studies tested the effects of steady-state treatment with desvenlafaxine (50–400 mg/d) on the pharmacokinetics of cytochrome (CYP) 2D6 and/or CYP 3A4 substrate drugs, or the effect of CYP 3A4 inhibition on desvenlafaxine pharmacokinetics. The potential for DDIs mediated by the P-glycoprotein (P-gp) transporter was assessed in in vitro studies using Caco-2 monolayers. Data Extraction: Changes in area under the plasma concentration-time curve (AUC; CYP studies) and efflux (P-gp studies) were reviewed for potential DDIs in accordance with FDA criteria. Results: Desvenlafaxine coadministration had minimal effect on CYP 2D6 and/or 3A4 substrates per FDA criteria. Changes in AUC indicated either no interaction (90% confidence intervals for the ratio of AUC geometric least-squares means [GM] within 80%–125%) or weak inhibition (AUC GM ratio 125% to < 200%). Coadministration with ketoconazole resulted in a weak interaction with desvenlafaxine (AUC GM ratio of 143%). Desvenlafaxine was not a substrate (efflux ratio < 2) or inhibitor (50% inhibitory drug concentration values > 250 ?M) of P-gp. Conclusions: A 2-step process based on FDA guidance can be used first to determine whether a pharmacokinetically mediated interaction occurs and then to assess the potential clinical significance of the DDI. In the case of the drug tested in this series of studies, the potential for clinically meaningful DDIs mediated by CYP 2D6, CYP 3A4, or P-gp was found to be low. PMID:26445693

  8. The distribution of controlled drugs on banknotes via counting machines.

    PubMed

    Carter, James F; Sleeman, Richard; Parry, Joanna

    2003-03-27

    Bundles of paper, similar to sterling banknotes, were counted in banks in England and Wales. Subsequent analysis showed that the counting process, both by machine and by hand, transferred nanogram amounts of cocaine to the paper. Crystalline material, similar to cocaine hydrochloride, could be observed on the surface of the paper following counting. The geographical distribution of contamination broadly followed Government statistics for cocaine usage within the UK. Diacetylmorphine, Delta(9)-tetrahydrocannabinol (THC) and 3,4-methylenedioxymethylamphetamine (MDMA) were not detected during this study. PMID:12711189

  9. Causality assessment for suspected DILI during clinical phases of drug development.

    PubMed

    Regev, Arie; Seeff, Leonard B; Merz, Michael; Ormarsdottir, Sif; Aithal, Guruprasad P; Gallivan, Jim; Watkins, Paul B

    2014-11-01

    Causality assessment is a critical step in establishing the diagnosis of drug induced liver injury (DILI) during drug development. DILI may resemble almost any type of liver disease, and often presents a serious challenge to clinical investigators and drug makers. The diagnosis of DILI is largely based upon a combination of a compatible clinical course, exclusion of all other reasonable causes, resemblance of clinical and pathological features to known features of liver injury due to the drug (i.e., "drug's signature"), and incidence of liver injury among patients treated with the drug compared to placebo or comparator. Causality assessment for suspected DILI is currently performed using either evaluation by physicians with expertise in liver disorders (i.e., expert opinion) or standardized scoring instruments such as the Roussel Uclaf Causality Assessment Method (RUCAM). Both approaches are widely used in the post marketing setting. Causality assessment based on expert opinion is considered superior to standardized instruments such as RUCAM, in the setting of drug development, and is currently the preferred approach during clinical trials. There is a need for a systematic revision of RUCAM that will render it more suitable for the setting of clinical trials and drug development. Careful monitoring and meticulous data collection during clinical trials are essential in all cases with established liver injury to allow for a proper causality assessment. A workshop was convened to discuss best practices for the assessment of drug-induced liver injury (DILI) in clinical trials. This publication is based on the conclusions of this workshop. PMID:25352327

  10. Assessment of Drug Transporter Function Using Fluorescent Cell Imaging

    PubMed Central

    Bircsak, Kristin M.; Gibson, Christopher J.; Robey, Robert W.

    2013-01-01

    ATP-binding cassette (ABC) proteins, including the breast cancer resistance protein (BCRP) and the multidrug resistance proteins (MDRs), actively transport structurally diverse chemicals from a number of tissues. Moreover, transporters are being increasingly cited as mediators of clinically relevant drug-drug interactions. The potential outcomes of concomitantly administering two drugs that interact at the same transporter include altered disposition and toxicity and/or efficacy of one or both of the drugs. Research demonstrating the role of transporters in clinical pharmacokinetics has shed light on the need for in vitro screening methods that detect drug-transporter interactions during preclinical development. This paper describes a cell-based model for the detection of functional inhibitors of BCRP and MDR1 by measuring fluorescent substrate accumulation in suspended cells that overexpress or endogenously express these proteins using an automated cell counter. An alternate protocol is provided describing the use of a spectrophotometer with fluorescence detection capabilities to identify functional inhibitors of BCRP and MDR1 in transporter overexpressing cells. While a spectrophotometer is available in most laboratories, an automatic cell counter offers convenience, sensitivity, and speed in measuring the cellular accumulation of fluorescent substrates and identification of novel inhibitors. PMID:24510579

  11. Impact of biomarker development on drug safety assessment

    SciTech Connect

    Marrer, Estelle; Dieterle, Frank

    2010-03-01

    Drug safety has always been a key aspect of drug development. Recently, the Vioxx case and several cases of serious adverse events being linked to high-profile products have increased the importance of drug safety, especially in the eyes of drug development companies and global regulatory agencies. Safety biomarkers are increasingly being seen as helping to provide the clarity, predictability, and certainty needed to gain confidence in decision making: early-stage projects can be stopped quicker, late-stage projects become less risky. Public and private organizations are investing heavily in terms of time, money and manpower on safety biomarker development. An illustrative and 'door opening' safety biomarker success story is the recent recognition of kidney safety biomarkers for pre-clinical and limited translational contexts by FDA and EMEA. This milestone achieved for kidney biomarkers and the 'know how' acquired is being transferred to other organ toxicities, namely liver, heart, vascular system. New technologies and molecular-based approaches, i.e., molecular pathology as a complement to the classical toolbox, allow promising discoveries in the safety biomarker field. This review will focus on the utility and use of safety biomarkers all along drug development, highlighting the present gaps and opportunities identified in organ toxicity monitoring. A last part will be dedicated to safety biomarker development in general, from identification to diagnostic tests, using the kidney safety biomarkers success as an illustrative example.

  12. Opinion: Assessing the Barriers to Image Guided Drug Delivery

    PubMed Central

    Lanza, Gregory M.; Moonen, Chrit; Baker, James R.; Chang, Esther; Cheng, Zheng; Grodzinski, Piotr; Ferrara, Katherine; Hynynen, Kullervo; Kelloff, Gary; Koo Lee, Yong-Eun; Patri, Anil K; Sept, David; Schnitzer, Jan E.; Wood, Bradford J.; Zhang, Miqin; Zheng, Gang; Farahani, Keyvan

    2014-01-01

    Imaging has become a cornerstone for medical diagnosis and the guidance of patient management. A new field called Image Guided Drug Delivery (IGDD) now combines the vast potential of the radiological sciences with the delivery of treatment and promises to fulfill the vision of personalized medicine. Whether imaging is used to deliver focused energy to drug-laden particles for enhanced, local drug release around tumors, or it is invoked in the context of nanoparticle-based agents to quantify distinctive biomarkers that could risk-stratify patients for improved targeted drug delivery efficiency, the overarching goal of IGDD is to use imaging to maximize effective therapy in diseased tissues and to minimize systemic drug exposure in order to reduce toxicities. Over the last several years innumerable reports and reviews covering the gamut of IGDD technologies have been published, but inadequate attention has been directed towards identifying and addressing the barriers limiting clinical translation. In this consensus opinion, the opportunities and challenges impacting the clinical realization of IGDD-based personalized medicine were discussed as a panel and recommendations were proffered to accelerate the field forward. PMID:24339356

  13. Assessing the barriers to image-guided drug delivery.

    PubMed

    Lanza, Gregory M; Moonen, Chrit; Baker, James R; Chang, Esther; Cheng, Zheng; Grodzinski, Piotr; Ferrara, Katherine; Hynynen, Kullervo; Kelloff, Gary; Lee, Yong-Eun Koo; Patri, Anil K; Sept, David; Schnitzer, Jan E; Wood, Bradford J; Zhang, Miqin; Zheng, Gang; Farahani, Keyvan

    2014-01-01

    Imaging has become a cornerstone for medical diagnosis and the guidance of patient management. A new field called image-guided drug delivery (IGDD) now combines the vast potential of the radiological sciences with the delivery of treatment and promises to fulfill the vision of personalized medicine. Whether imaging is used to deliver focused energy to drug-laden particles for enhanced, local drug release around tumors, or it is invoked in the context of nanoparticle-based agents to quantify distinctive biomarkers that could risk stratify patients for improved targeted drug delivery efficiency, the overarching goal of IGDD is to use imaging to maximize effective therapy in diseased tissues and to minimize systemic drug exposure in order to reduce toxicities. Over the last several years, innumerable reports and reviews covering the gamut of IGDD technologies have been published, but inadequate attention has been directed toward identifying and addressing the barriers limiting clinical translation. In this consensus opinion, the opportunities and challenges impacting the clinical realization of IGDD-based personalized medicine were discussed as a panel and recommendations were proffered to accelerate the field forward. PMID:24339356

  14. Evolution of the Food and Drug Administration approach to liver safety assessment for new drugs: current status and challenges.

    PubMed

    Senior, John R

    2014-11-01

    Prompted by approval in 1997 of troglitazone and bromfenac, two drugs that promptly began to show serious and sometimes fatal liver toxicity, we began at the Food and Drug Administration (FDA) a series of annual conferences in 1999 to consider issues of drug-induced liver injury (DILI). First inviting reviewers of new drug applications we opened the audiences in 2001 to pharmaceutical industry and academic consultants to industry and FDA, and slides shown at the meetings were posted on the internet to be available at the website of the American Association for the Study of Liver Diseases (AASLD)-go to ( http://www.aasld.org/dili/Pages/default.aspx ). Observations by Dr. Hyman J. Zimmerman that "drug-induced hepatocellular jaundice is a serious lesion" with possible mortality formed a basis for developing a computer program to plot peak serum values for alanine aminotransferase (ALT) and total bilirubin (TBL) in an x-y log-log graph for all subjects enrolled in clinical trials. This program had the capability to show the time course of all liver tests for individuals who had both hepatocellular injury and reduced whole liver function, plus clinical narratives to diagnose the severity and most likely cause of the abnormalities. We called the program eDISH (for evaluation of Drug-Induced Serious Hepatotoxicity), and began in 2004 to use it to assess DILI in clinical trial subjects. From 2008, comments made by the presenters at the conferences about their slides and ensuing discussions have been added to the website. All this has raised awareness of the problem, and since 1997, the FDA has not had to withdraw a single drug because of post-marketing hepatotoxicity. Many issues still remain to be resolved; among the most controversial is the best method to estimate likelihood that a given liver injury was actually caused by the drug in question. On November 9, 2012, a workshop was convened to discuss the best practices for the assessment of drug-induced liver injury (DILI) in clinical trials. PMID:25352324

  15. Assessment of the Biological Effects of a Multifunctional Nano-Drug-Carrier and Its Encapsulated Drugs.

    PubMed

    Song, Yipeng; Zhao, Ruifang; Hu, Yili; Hao, Fuhua; Li, Ning; Nie, Guangjun; Tang, Huiru; Wang, Yulan

    2015-12-01

    Polymer-nanoparticle-encapsulated doxorubicin (DOX) and paclitaxel (TAX) have the potential for novel therapeutic use against cancer in the clinic. However, the systemic biological effect of the nanoparticle material, namely, methoxypoly(ethylene glycol)-poly(lactide-co-glycolide) (mPEG-PLGA), and its encapsulated drugs have not been fully studied. We have applied NMR-based metabonomics methodology to characterize and analyze the systemic metabolic changes in mice after being exposed to mPEG-PLGA, mPEG-PLGA-encapsulated DOX and TAX (NP-D/T), and their free forms. The study revealed that mPEG-PLGA exposure only induces temporary and slight metabolic alternations and that there are detoxification effects of nanoparticle packed with D/T drugs on the heart when comparing with free-form D/T drugs. Both NP-D/T and their free forms induce a shift in energy metabolism, stimulate antioxidation pathways, and disturb the gut microbial activity of the host. However, mPEG-PLGA packaging can relieve the energy metabolism inhibition and decrease the activation of antioxidation pathways caused by D/T exposure. These findings provide a holistic insight into the biological effect of polymer nanoparticle and nanoparticle-encapsulated drugs. This study also furthers our understanding of the molecular mechanisms involved in the amelioration effects of mPEG-PLGA packaging on the toxicity of the incorporated drugs. PMID:26531143

  16. Influence of drug distribution and solubility on release from geopolymer pellets--a finite element method study.

    PubMed

    Jämstorp, Erik; Strømme, Maria; Bredenberg, Susanne

    2012-05-01

    This study investigates the influence of drug solubility and distribution on its release from inert geopolymer pellets of three different sizes (1.5 × 1.5, 3 × 6, and 6 × 6 mm), having the same geopolymer composition and containing highly potent opioid fentanyl, sumatriptan, theophylline, or saccharin. Scanning electron microscopy, nitrogen sorption, drug solubility, permeation, and release experiments were performed, and estimates of the drug diffusion coefficients and solubilities in the geopolymer matrix were derived with the aid of finite element method (FEM). FEM was further employed to investigate the effect of a nonuniform drug distribution on the drug release profile. When inspecting the release profiles for each drug, it was observed that their solubilities in the geopolymer matrix imposed a much greater influence on the drug release rate than their diffusion coefficients. Concentrating the initial drug load in FEM into nonuniformly distributed drug regions inside the matrix created drug release profiles that more closely resembled experimental data than an FEM-simulated uniform drug distribution did. The presented FEM simulations and visualization of drug release from geopolymers under varying initial and dynamic conditions should open up for more systematic studies of additional factors that influence the drug release profile from porous delivery vehicles. PMID:22308066

  17. Preclinical assessment of proconvulsant drug activity and its relevance for predicting adverse events in humans.

    PubMed

    Löscher, Wolfgang

    2009-05-21

    Safety pharmacology studies, which are performed before first studies with investigational drugs in humans, often include experiments on proconvulsant drug activity, because such drugs are thought to promote seizures by decreasing seizure threshold. A commonly used model for the assessment of proconvulsant activity of investigational or marketed drugs is the timed intravenous pentylenetetrazole (PTZ) infusion seizure test, in which the latency to myoclonic or clonic seizures is determined by PTZ infusion in mice or rats. This test provides an extremely sensitive parametric method for assessing seizure threshold and allows detecting both anticonvulsant and proconvulsant drug effects. The aim of this review is to critically review the concept of "proconvulsant" drug activity and discuss data obtained by the PTZ and other seizure threshold tests as well as the various factors that may affect seizure threshold determinations. Furthermore, preclinical and clinical data on proconvulsant drug activity are compared. It is concluded that a battery of different tests is needed to provide the most reliable conclusions about the proconvulsant profile, if any, of drugs. Furthermore, misconceptions regarding proconvulsant drug effects, which can result in the undertreatment of brain diseases, are discussed. PMID:19292981

  18. Interrogating the relationship between rat in vivo tissue distribution and drug property data for >200 structurally unrelated molecules

    PubMed Central

    Harrell, Andrew W; Sychterz, Caroline; Ho, May Y; Weber, Andrew; Valko, Klara; Negash, Kitaw

    2015-01-01

    The ability to explain distribution patterns from drug physicochemical properties and binding characteristics has been explored for more than 200 compounds by interrogating data from quantitative whole body autoradiography studies (QWBA). These in vivo outcomes have been compared to in silico and in vitro drug property data to determine the most influential properties governing drug distribution. Consistent with current knowledge, in vivo distribution was most influenced by ionization state and lipophilicity which in turn affected phospholipid and plasma protein binding. Basic and neutral molecules were generally better distributed than acidic counterparts demonstrating weaker plasma protein and stronger phospholipid binding. The influence of phospholipid binding was particularly evident in tissues with high phospholipid content like spleen and lung. Conversely, poorer distribution of acidic drugs was associated with stronger plasma protein and weaker phospholipid binding. The distribution of a proportion of acidic drugs was enhanced, however, in tissues known to express anionic uptake transporters such as the liver and kidney. Greatest distribution was observed into melanin containing tissues of the eye, most likely due to melanin binding. Basic molecules were consistently better distributed into parts of the eye and skin containing melanin than those without. The data, therefore, suggest that drug binding to macromolecules strongly influences the distribution of total drug for a large proportion of molecules in most tissues. Reducing lipophilicity, a strategy often used in discovery to optimize pharmacokinetic properties such as absorption and clearance, also decreased the influence of nonspecific binding on drug distribution. PMID:26516585

  19. Distribution and drug resistance profile of methicillin-resistant Staphylococcus aureus after orthopaedic surgery.

    PubMed

    Song, Wen Chao; Zhang, Si Sen; Gong, Yu Hong

    2015-05-01

    This paper is aimed to comprehend clinical distribution and drug-resistance situation of methicillin-resistant Staphylococcus aureus. This study applied automatic microbe instrument Microscan W/A 96 for strain identification and drug susceptibility screening on the isolated strains. It was found that 312 MRSA strains were isolated in three years, which account for 58.1% of Staphylococcus aureus. MRSA were mainly focused in wound secretion, purulent sputum and prostatic fluid and a few of them were isolated from blood specimens; Endemic area distribution was mainly located in intensive care unit, neurosurgery, respiratory department, dermatology, orthopaedic burns and orthopaedics. MRSA strains showed high drug resistance of 82.37%~100% to most of the antibiotics including vancomycin, cotrimoxazole and rifampicin. Strain was 100% resistance towards ampicillin, amoxicillin/acid, cefalotin, cefazolin, tienam, benzylpenicillin, penicillin and tetracycline and 90% strains resisted clindamycin, cefotaxime, clarithromycin and gentamicin. PMID:26051737

  20. 10 CFR 32.21 - Radioactive drug: Manufacture, preparation, or transfer for commercial distribution of capsules...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Radioactive drug: Manufacture, preparation, or transfer for commercial distribution of capsules containing carbon-14 urea each for âin vivoâ diagnostic use for humans to persons exempt from licensing; Requirements for a license. 32.21 Section 32.21 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC...

  1. 10 CFR 32.21 - Radioactive drug: Manufacture, preparation, or transfer for commercial distribution of capsules...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Radioactive drug: Manufacture, preparation, or transfer for commercial distribution of capsules containing carbon-14 urea each for âin vivoâ diagnostic use for humans to persons exempt from licensing; Requirements for a license. 32.21 Section 32.21 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC...

  2. 10 CFR 32.21 - Radioactive drug: Manufacture, preparation, or transfer for commercial distribution of capsules...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Radioactive drug: Manufacture, preparation, or transfer for commercial distribution of capsules containing carbon-14 urea each for âin vivoâ diagnostic use for humans to persons exempt from licensing; Requirements for a license. 32.21 Section 32.21 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC...

  3. 10 CFR 32.21 - Radioactive drug: Manufacture, preparation, or transfer for commercial distribution of capsules...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Radioactive drug: Manufacture, preparation, or transfer for commercial distribution of capsules containing carbon-14 urea each for âin vivoâ diagnostic use for humans to persons exempt from licensing; Requirements for a license. 32.21 Section 32.21 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC...

  4. 45 CFR 156.295 - Prescription drug distribution and cost reporting.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 1 2012-10-01 2012-10-01 false Prescription drug distribution and cost reporting. 156.295 Section 156.295 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS HEALTH INSURANCE ISSUER STANDARDS UNDER THE AFFORDABLE CARE ACT, INCLUDING STANDARDS RELATED TO EXCHANGES Qualified...

  5. 75 FR 52765 - Development and Distribution of Patient Medication Information for Prescription Drugs; Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-27

    ... comment (75 FR 23775, May 4, 2010) and expert panel input, FDA is also finalizing the design of the...'s Risk Communication Advisory Committee meeting, held on February 26 and 27, 2009 (73 FR 74505... SERVICES Food and Drug Administration Development and Distribution of Patient Medication Information...

  6. Neuroleptic drugs in the human brain: clinical impact of persistence and region-specific distribution.

    PubMed

    Kornhuber, Johannes; Wiltfang, Jens; Riederer, Peter; Bleich, Stefan

    2006-08-01

    After discontinuation of neuroleptic agents, their effects are still present for a long time. The exact underlaying mechanisms are still unclear. In two previous studies we measured the concentrations and region-specific distribution of haloperidol (Kornhuber et al. 1999) and levomepromazine (Kornhuber et al. 2006) in postmortem human brain tissues. The aim of the present paper is to compare the results of these two studies. Even after short-term treatment, haloperidol and levomepromazine concentrations reach high levels in human brain tissue. Haloperidol concentrations in brain tissue are 10-30 times higher than the optimum serum concentrations in the treatment of schizophrenia. The brain-to-blood concentration ratio of levomepromazine is about 10. The estimated elimination half-life of these drugs in brain tissue are 6.8 days (haloperidol), 7.9 days (levomepromazine) and 27.8 days for the metabolite desmethyl-levomepromazine, respectively. After two half-lives (about 2 weeks), a considerable amount of drug remains in brain tissue. Haloperidol concentrations appeared to be homogeneously distributed across different brain areas, whereas levomepromazine shows a region-specific distribution, with highest values in the basal ganglia. The persistence of neuroleptic drugs in the human brain might explain their prolonged effects and side effects. The region-specific distribution of levomepromazine may increase our understanding of both the preferential toxicity of neuroleptic drugs against basal ganglia structures and higher basal ganglia volumes in patients treated with neuroleptics. PMID:16788768

  7. Comparison of equilibrium and non-equilibrium distribution coefficients for the human drug carbamazepine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The distribution coefficient (KD) for the human drug carbamazepine was measured using a non-equilibrium technique. Repacked soil columns were prepared using an Airport silt loam (Typic Natrustalf) with an average organic matter content of 2.45%. Carbamazepine solutions were then leached through th...

  8. Training Needs of Rehabilitation Counselors concerning Alcohol and Other Drugs Abuse Assessment and Treatment

    ERIC Educational Resources Information Center

    Ong, Lee Za; Cardoso, Elizabeth; Chan, Fong; Chronister, Julie; Chou, Chih Chin

    2007-01-01

    Forty-two rehabilitation counselors participated in a study regarding perceived training needs concerning alcohol and other drug abuse (AODA) treatment and assessment. Participants reported that 85% of consumers with whom they worked had AODA issues, yet over half rated their graduate training in AODA treatment and assessment as poor, and their…

  9. Establishing the Validity of the Personality Assessment Inventory Drug and Alcohol Scales in a Corrections Sample

    ERIC Educational Resources Information Center

    Patry, Marc W.; Magaletta, Philip R.; Diamond, Pamela M.; Weinman, Beth A.

    2011-01-01

    Although not originally designed for implementation in correctional settings, researchers and clinicians have begun to use the Personality Assessment Inventory (PAI) to assess offenders. A relatively small number of studies have made attempts to validate the alcohol and drug abuse scales of the PAI, and only a very few studies have validated those…

  10. Quantitative Assessment of Distributed Energy Resource Benefits

    SciTech Connect

    Hadley, S.W.

    2003-05-22

    Distributed energy resources (DER) offer many benefits, some of which are readily quantified. Other benefits, however, are less easily quantifiable because they may require site-specific information about the DER project or analysis of the electrical system to which the DER is connected. The purpose of this study is to provide analytical insight into several of the more difficult calculations, using the PJM power pool as an example. This power pool contains most of Pennsylvania, New Jersey, Maryland, and Delaware. The techniques used here could be applied elsewhere, and the insights from this work may encourage various stakeholders to more actively pursue DER markets or to reduce obstacles that prevent the full realization of its benefits. This report describes methodologies used to quantify each of the benefits listed in Table ES-1. These methodologies include bulk power pool analyses, regional and national marginal cost evaluations, as well as a more traditional cost-benefit approach for DER owners. The methodologies cannot however determine which stakeholder will receive the benefits; that must be determined by regulators and legislators, and can vary from one location to another.

  11. Imaging of drug loading distributions in individual microspheres of calcium silicate hydrate - an X-ray spectromicroscopy study

    NASA Astrophysics Data System (ADS)

    Guo, Xiaoxuan; Wang, Zhiqiang; Wu, Jin; Wang, Jian; Zhu, Ying-Jie; Sham, Tsun-Kong

    2015-04-01

    Imaging is one of the most direct and ideal ways to track drug loading distributions in drug carriers on the molecular level, which will facilitate the optimization of drug carriers and drug loading capacities. Herein, we report the mapping of an individual mesoporous calcium silicate hydrate (CSH) microsphere before and after the loading of ibuprofen (IBU) and the interactions between drug carriers and drug molecules simultaneously by scanning transmission X-ray microscopy (STXM). Nanoscaled X-ray absorption near edge structure (XANES) spectroscopy clearly indicates that IBU is bonded to calcium and silicate sites via carboxylic acid groups. More importantly, STXM has been successfully used to determine the absolute thickness of IBU, revealing its distribution in the CSH microsphere.Imaging is one of the most direct and ideal ways to track drug loading distributions in drug carriers on the molecular level, which will facilitate the optimization of drug carriers and drug loading capacities. Herein, we report the mapping of an individual mesoporous calcium silicate hydrate (CSH) microsphere before and after the loading of ibuprofen (IBU) and the interactions between drug carriers and drug molecules simultaneously by scanning transmission X-ray microscopy (STXM). Nanoscaled X-ray absorption near edge structure (XANES) spectroscopy clearly indicates that IBU is bonded to calcium and silicate sites via carboxylic acid groups. More importantly, STXM has been successfully used to determine the absolute thickness of IBU, revealing its distribution in the CSH microsphere. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr07471h

  12. Application of GIS in water distribution system assessment.

    PubMed

    Sargaonkar, Aabha; Islam, Raisul

    2009-10-01

    Water distribution system (WDS) is the most important component of water supply chain--supplying water from source to consumer. When supply system is poorly maintained, contaminants enter into the supply pipes through cracks and this leads to significant public health risk. Being underground, pipe condition assessment is a difficult task. In this paper, a case study is presented for assessment of pipe condition in a water distribution network of Moinbagh area in Hyderabad (India). The mathematical model-Pipe Condition Assessment (PCA) Model was used, which utilizes GIS based maps of water distribution network, sewer network, drains and soil as input in addition to data on physical properties of the network as well as operational parameters. The application of PCA identified that only 3% pipes in the network were in bad condition. PMID:21117426

  13. Distribution of primaquine in human blood: Drug-binding to alpha 1-glycoprotein

    SciTech Connect

    Kennedy, E.; Frischer, H. )

    1990-12-01

    To clarify the distribution of the antimalarial primaquine in human blood, we measured the drug separately in the liquid, cellular, and ultrafiltrate phases. Washed red cells resuspended at a hematocrit of 0.4 were exposed to a submaximal therapeutic level of 250 ng/ml of carbon 14-labeled primaquine. The tracer was recovered quantitatively in separated plasma and red cells. Over 75% of the total labeled drug was found in red cells suspended in saline solution, but only 10% to 30% in red cells suspended in plasma. The plasma effect was not mediated by albumin. Studies with alpha 1-acid glycoprotein (AGP), tris(2-butoxyethyl)phosphate, an agent that displaces AGP-bound drugs, and cord blood known to have decreased AGP established that primaquine binds to physiologic amounts of the glycoprotein in plasma. Red cell primaquine concentration increased linearly as AGP level fell and as the free drug fraction rose. We suggest that clinical blood levels of primaquine include the red cell fraction or whole blood level because (1) erythrocytic primaquine is a sizable and highly variable component of the total drug in blood; (2) this component reflects directly the free drug in plasma, and inversely the extent of binding to AGP; (3) the amount of free primaquine may influence drug transport into specific tissues in vivo; and (4) fluctuations of AGP, an acute-phase reactant that increases greatly in patients with malaria and other infections, markedly affect the partition of primaquine in blood. Because AGP binds many basic drugs, unrecognized primaquine-drug interactions may exist.

  14. The association between sterilizing activity and drug distribution into tuberculosis lesions.

    PubMed

    Prideaux, Brendan; Via, Laura E; Zimmerman, Matthew D; Eum, Seokyong; Sarathy, Jansy; O'Brien, Paul; Chen, Chao; Kaya, Firat; Weiner, Danielle M; Chen, Pei-Yu; Song, Taeksun; Lee, Myungsun; Shim, Tae Sun; Cho, Jeong Su; Kim, Wooshik; Cho, Sang Nae; Olivier, Kenneth N; Barry, Clifton E; Dartois, Véronique

    2015-10-01

    Finding new treatment-shortening antibiotics to improve cure rates and curb the alarming emergence of drug resistance is the major objective of tuberculosis (TB) drug development. Using a matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging suite in a biosafety containment facility, we show that the key sterilizing drugs rifampicin and pyrazinamide efficiently penetrate the sites of TB infection in lung lesions. Rifampicin even accumulates in necrotic caseum, a critical lesion site where persisting tubercle bacilli reside. In contrast, moxifloxacin, which is active in vitro against a subpopulation of Mycobacterium tuberculosis that persists in specific niches under drug pressure and has achieved treatment shortening in mice, does not diffuse well in caseum, concordant with its failure to shorten therapy in recent clinical trials. We suggest that such differential spatial distribution and kinetics of accumulation in lesions may create temporal and spatial windows of monotherapy in specific niches, allowing the gradual development of multidrug-resistant TB. We propose an alternative working model to prioritize new antibiotic regimens based on quantitative and spatial distribution of TB drugs in the major lesion types found in human lungs. The finding that lesion penetration may contribute to treatment outcome has wide implications for TB. PMID:26343800

  15. Prediction and Prevention of Prescription Drug Abuse: Role of Preclinical Assessment of Substance Abuse Liability

    PubMed Central

    Marusich, Julie A.; Lefever, Timothy W.; Novak, Scott P.; Blough, Bruce E.; Wiley, Jenny L.

    2013-01-01

    In 2011, the prevalence of prescription drug abuse exceeded that of any other illicit drug except marijuana. Consequently, efforts to curtail abuse of new medications should begin during the drug development process, where abuse liability can be identified and addressed before a candidate medication has widespread use. The first step in this process is scheduling with the Drug Enforcement Agency so that legal access is appropriately restricted, dependent upon levels of abuse risk and medical benefit. To facilitate scheduling, the Food and Drug Administration (FDA) has published guidance for industry that describes assessment of abuse liability. The purpose of this paper is to review methods that may be used to satisfy the FDA’s regulatory requirements for animal behavioral and dependence pharmacology. Methods include psychomotor activity, self-administration (an animal model of the rewarding effects of a drug), drug discrimination (an animal model of the subjective effects of a drug), and evaluation of tolerance and dependence. Data from tests conducted at RTI with known drugs of abuse illustrate typical results, and demonstrate that RTI is capable of performing these tests. While using preclinical data to predict abuse liability is an imperfect process, it has substantial predictive validity. The ultimate goal is to increase consumer safety through appropriate scheduling of new medications. PMID:24008590

  16. Assessment of Adverse Drug Reactions Based on Spontaneous Signals at Secondary Care Public Hospital

    PubMed Central

    Ponnusankar, S.; Tejaswini, M.; Chaitanya, M.

    2015-01-01

    Adverse drug reactions are considered to be among the leading causes of morbidity and mortality. Approximately 5-25% of hospital admissions are due to adverse drug reactions and 6-15% of hospitalized patients experience serious adverse drug reactions, causing significant prolongation of hospital stay. Thus this study was aimed at determining adverse drug reactions by conducting spontaneous reporting in secondary care Govt. District Head Quarters Hospital at Ooty. A prospective Spontaneous Adverse Drug Reaction reporting study was conducted over a period of 12 months from July 2012 to June 2013. The assessment, categorization, causality, severity and preventability were assessed using standard criteria. A total of 47 suspected adverse drug reactions were reported during the study period. Over all incidences was 1.29% among the study population. Antibiotics (31.91%) were the class of drug most commonly involved, while ciprofloxacin (14.89%) was the most frequently reported. Type H (Hypersensitivity) reactions (51.06%) accounted for majority of the reports and a greater share of the adverse drug reactions are probable (89.36%) based on causality assessment. Mild reactions accounted 82.97% based on modified Hartwig and Siegel severity scale. In 76.59% of the reports, the reaction was considered to be preventable based on Schumock and Thornton preventability scale. The implementation of monitoring based on spontaneous reporting will be useful for the detection and evaluation is associated with increase in morbidity and duration of hospitalization. This study also has established the vital role of clinical pharmacist in the adverse drug reaction monitoring program.

  17. [Drugs use assessment in a group of bus drivers].

    PubMed

    Maccà, I; Maso, S; Marcuzzo, G; Bartolucci, G B

    2012-01-01

    Bus driver is one of those tasks inherent transport activity, which involves special risks to safety and health of others and for which it is necessary, according to art. 41 of Decree No. 81/08, to check the consumption of psychoactive substances during the health surveillance. This assumption was investigated in a group of 461 bus drivers of a large trucking company. In medical history, one subject reported a previous history of opiate addiction and another, in the past, occasional taking of cannabis, and at the time of the visit, in no cases the objectivity has shown intoxication or abstinence signs, or signs of parenteral injection. Laboratory tests were found positive in one case of screening texts, not confirmed by subsequent laboratory analysis and a case of positive analysis for confirmation. The worker, temporarily suspended from driving and taken over by the Service for Drug Addiction of competence, was then reinstated in his job, having held that the absence of drug addiction. PMID:23405659

  18. Assessment of intestinal availability (FG) of substrate drugs of cytochrome p450s by analyzing changes in pharmacokinetic properties caused by drug-drug interactions.

    PubMed

    Hisaka, Akihiro; Nakamura, Mikiko; Tsukihashi, Ayako; Koh, Saori; Suzuki, Hiroshi

    2014-10-01

    In this study, we developed the drug-drug interaction (DDI) method as a new assessment technique of intestinal availability (F(G), the fraction of drug transferred from the intestinal enterocytes into the liver, escaping from intestinal metabolism) based on the clearance theory. This method evaluates F(G) from changes caused by DDIs in the area under the blood concentration-time curve and in the elimination half-life of victim drugs. Application of the DDI method to data from the literature revealed that the mean and S.D. of F(G) values for 20 substrate drugs of CYP3A was 0.56 ± 0.29, whereas that for 8 substrate drugs of CYP2C9, CYP2C19, and CYP2D6 was 0.86 ± 0.11. These results were consistent with the fact that intestinal metabolism is mediated predominantly by CYP3A. The DDI method showed reasonable correlations with the conventional i.v./p.o. method and the grape fruit juice (GFJ) method (coefficients of determination of 0.41 and 0.81, respectively). The i.v./p.o. method was more susceptible to fluctuations in the hepatic blood flow rate compared with the DDI and GFJ methods. The DDI method evaluates F(G) separating from the absorption ratio (F(A)) although it requires approximation of F(A). Since preciseness of approximation of F(A) does not greatly affect the evaluation of F(G) by the DDI method, we proposed a reasonable approximation method of F(A) for the evaluation of F(G) in the DDI method. The DDI method would be applicable to a broad range of situations in which various DDI data are utilizable. PMID:25061161

  19. Perpetrators of pharmacokinetic drug–drug interactions arising from altered cytochrome P450 activity: a criteria-based assessment

    PubMed Central

    Polasek, Thomas M; Lin, Frank P Y; Miners, John O; Doogue, Matthew P

    2011-01-01

    AIMS To catalogue the perpetrators of CYP-mediated pharmacokinetic drug–drug interactions (PK-DDIs) using clinically relevant criteria, and to compare this with an analogous catalogue. METHODS Candidate inhibitors and inducers of CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A (‘perpetrators’) were evaluated using published clinical pharmacokinetic interaction studies. Studies were selected on the basis of ?six human subjects, use of a validated in vivo probe substrate for the CYP enzyme, and clinically relevant dosing. Inhibitors were described according to the FDA classifications of strong, moderate or weak, whereas inducers were classified as major (?twofold decrease in AUC) or weak (Drug Interaction Table (CDIT) were compared with the ‘accepted’ major perpetrators. RESULTS From a list of 216 candidate drugs (349 CYP-perpetrator pairs, CYP-PPs), 36 inhibitors and eight inducers were accepted as major perpetrators of PK-DDIs, resulting in 58 CYP-PPs. In comparison, the clinical version of the CDIT had a sensitivity of 33% and a positive predictive value of 68%. One hundred and ninety-nine CYP-PPs were rejected as major perpetrators, and 92 CYP-PPs had insufficient published human pharmacokinetic data for robust classification. CONCLUSIONS Using a criteria-based assessment, the number of drugs that are proven or likely major perpetrators of CYP-mediated PK-DDIs is relatively small. Current clinical decision support on PK-DDIs is inconsistent with the published evidence and can be improved using simple criteria. PMID:21223357

  20. Condition Assessment Technologies for Water Transmission and Distribution Systems

    EPA Science Inventory

    As part of the U.S. Environmental Protection Agency’s (EPA’s) Aging Water Infrastructure Research Program, this research was conducted to identify and characterize the state of the technology for structural condition assessment of drinking water transmission and distribution syst...

  1. Condition Assessment of Drinking Water Transmission and Distribution Systems

    EPA Science Inventory

    Condition assessment of water transmission and distribution mains is the collection of data and information through direct and/or indirect methods, followed by analysis of the data and information, to make a determination of the current and/or future structural, water quality, an...

  2. Distribution of Drug Molecules in Lipid Membranes: Neutron Diffraction and MD Simulations.

    NASA Astrophysics Data System (ADS)

    Boggara, Mohan; Mihailescu, Ella; Krishnamoorti, Ramanan

    2009-03-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) e.g. Aspirin and Ibuprofen, with chronic usage cause gastro intestinal (GI) toxicity. It has been shown experimentally that NSAIDs pre-associated with phospholipids reduce the GI toxicity and also increase the therapeutic activity of these drugs compared to the unmodified ones. In this study, using neutron diffraction, the DOPC lipid bilayer structure (with and without drug) as well as the distribution of a model NSAID (Ibuprofen) as a function of its position along the membrane normal was obtained at sub-nanometer resolution. It was found that the bilayer thickness reduces as the drug is added. Further, the results are successfully compared with atomistic Molecular Dynamics simulations. Based on this successful comparison and motivated by atomic details from MD, quasi-molecular modeling of the lipid membrane is being carried out and will be presented. The above study is expected to provide an effective methodology to design drug delivery nanoparticles based on a variety of soft condensed matter such as lipids or polymers.

  3. Rapid assessment of drug use and sexual HIV risk patterns among vulnerable drug-using populations in Cape Town, Durban and Pretoria, South Africa.

    PubMed

    Parry, Charles; Petersen, Petal; Carney, Tara; Dewing, Sarah; Needle, Richard

    2008-09-01

    This exploratory study examines the links between drug use and high-risk sexual practices and HIV in vulnerable drug-using populations in South Africa, including commercial sex workers (CSWs), men who have sex with men (MSM), injecting drug users (IDUs) and non-injecting drug users who are not CSWs or MSM (NIDUs). A rapid assessment ethnographic study was undertaken using observation, mapping, key informant interviews and focus groups in known 'hotspots' for drug use and sexual risk in Cape Town, Durban and Pretoria. Key informant (KI) and focus group interviews involved drug users and service providers. Purposeful snowball sampling and street intercepts were used to recruit drug users. Outcome measures included drug-related sexual HIV risk behaviour, and risk behaviour related to injection drug use, as well as issues related to service use. HIV testing of drug-using KIs was conducted using the SmartCheck Rapid HIV-1 Antibody Test. Non-injection drug use (mainly cannabis, methaqualone, crack cocaine and crystal methamphetamine) and injection drug use (mainly heroin) was occurring in these cities. Drug users report selling sex for money to buy drugs, and CSWs used drugs before, during and after sex. Most (70%) of the drug-using KIs offered HIV testing accepted and 28% were positive, with rates highest among CSWs and MSM. IDUs reported engaging in needle sharing and needle disposal practices that put them and others at risk for contracting HIV. There was a widespread lack of awareness about where to access HIV treatment and preventive services, and numerous barriers to accessing appropriate HIV and drug-intervention services were reported. Multiple risk behaviours of vulnerable populations and lack of access to HIV prevention services could accelerate the diffusion of HIV. Targeted interventions could play an important role in limiting the spread of HIV in and through these under-reached and vulnerable populations. PMID:18979044

  4. Criteria for assessing high-priority drug-drug interactions for clinical decision support in electronic health records

    PubMed Central

    2013-01-01

    Background High override rates for drug-drug interaction (DDI) alerts in electronic health records (EHRs) result in the potentially dangerous consequence of providers ignoring clinically significant alerts. Lack of uniformity of criteria for determining the severity or validity of these interactions often results in discrepancies in how these are evaluated. The purpose of this study was to identify a set of criteria for assessing DDIs that should be used for the generation of clinical decision support (CDS) alerts in EHRs. Methods We conducted a 20-year systematic literature review of MEDLINE and EMBASE to identify characteristics of high-priority DDIs. These criteria were validated by an expert panel consisting of medication knowledge base vendors, EHR vendors, in-house knowledge base developers from academic medical centers, and both federal and private agencies involved in the regulation of medication use. Results Forty-four articles met the inclusion criteria for assessing characteristics of high-priority DDIs. The panel considered five criteria to be most important when assessing an interaction- Severity, Probability, Clinical Implications of the interaction, Patient characteristics, and the Evidence supporting the interaction. In addition, the panel identified barriers and considerations for being able to utilize these criteria in medication knowledge bases used by EHRs. Conclusions A multi-dimensional approach is needed to understanding the importance of an interaction for inclusion in medication knowledge bases for the purpose of CDS alerting. The criteria identified in this study can serve as a first step towards a uniform approach in assessing which interactions are critical and warrant interruption of a provider’s workflow. PMID:23763856

  5. Rapid assessment response (RAR) study: drug use and health risk - Pretoria, South Africa

    PubMed Central

    2011-01-01

    Background Within a ten year period South Africa has developed a substantial illicit drug market. Data on HIV risk among drug using populations clearly indicate high levels of HIV risk behaviour due to the sharing of injecting equipment and/or drug-related unprotected sex. While there is international evidence on and experience with adequate responses, limited responses addressing drug use and drug-use-related HIV and other health risks are witnessed in South Africa. This study aimed to explore the emerging problem of drug-related HIV transmission and to stimulate the development of adequate health services for the drug users, by linking international expertise and local research. Methods A Rapid Assessment and Response (RAR) methodology was adopted for the study. For individual and focus group interviews a semi-structured questionnaire was utilised that addressed key issues. Interviews were conducted with a total of 84 key informant (KI) participants, 63 drug user KI participants (49 males, 14 females) and 21 KI service providers (8 male, 13 female). Results and Discussion Adverse living conditions and poor education levels were cited as making access to treatment harder, especially for those living in disadvantaged areas. Heroin was found to be the substance most available and used in a problematic way within the Pretoria area. Participants were not fully aware of the concrete health risks involved in drug use, and the vague ideas held appear not to allow for concrete measures to protect themselves. Knowledge with regards to substance related HIV/AIDS transmission is not yet widespread, with some information sources disseminating incorrect or unspecific information. Conclusions The implementation of pragmatic harm-reduction and other evidence-based public health care policies that are designed to reduce the harmful consequences associated with substance use and HIV/AIDS should be considered. HIV testing and treatment services also need to be made available in places accessed by drug users. PMID:21631928

  6. Effect of alpha-cyclodextrin on drug distribution studied by electrochemistry at interfaces between immiscible electrolyte solutions.

    PubMed

    Deryabina, Maria A; Hansen, Steen H; Østergaard, Jesper; Jensen, Henrik

    2009-05-21

    The description and understanding of noncovalent interactions and distribution of potential new drug compounds in an organism is of paramount importance for the successful development of new drugs. In this work, a new procedure based on electrochemistry at the interface between two immiscible electrolyte solutions (ITIES) for addressing and discriminating between drug compound/ligand interactions in aqueous solution and nonspecific ligand effects on oil-water distribution behavior has been developed. The procedure is demonstrated using five drug compounds with different physical chemical parameters and alpha-cyclodextrin as the aqueous phase ligand. Alpha-cyclodextrin was chosen as an aqueous phase ligand, as it is frequently used in drug formulations to enhance solubility and bioavailability of drug compounds. Supplementary capillary electrophoresis experiments provided more detailed information on alpha-cyclodextrin drug complexation and, in combination with the electrochemical studies, provided information on solvation effects affecting the oil-water distribution of the drug compounds. The use of ligand shift ion partition diagrams for data presentation is a convenient format for the visualization of ligand effects on distribution behavior of related drug compounds. PMID:19397256

  7. Chemical, genetic and structural assessment of pyridoxal kinase as a drug target in the African trypanosomemmi_8189 51..64

    E-print Network

    Schnaufer, Achim

    such as the need for parenteral administration, increasing treat- ment failures, possibly due to drug resistanceChemical, genetic and structural assessment of pyridoxal kinase as a drug target in the African of Biological Chemistry & Drug Discovery, College of Life Sciences, University of Dundee, Dundee, UK. Summary

  8. Assessing malaria drug resistance in US military areas of operation using microarrays.

    E-print Network

    Gleeson, Joseph G.

    Assessing malaria drug resistance in US military areas of operation using microarrays. A. Taylor Bright University of California, San Diego Background: Malaria inflicts an incredible burden of the developed world, roughly 40% of the world's population live in areas where malaria is endemic(1

  9. A Guide to Multicultural Drug Abuse Prevention: Needs Assessment. Series Booklet.

    ERIC Educational Resources Information Center

    Harrison-Burns, Bettye; And Others

    This guide is designed to help planners of drug abuse prevention programs for minority groups to assess the specific needs of their communities. Covered are: (1) sources of and methods of acquiring statistical and background information; (2) community survey techniques; (3) developing problem statements; (4) choosing a remedy; (5) writing a…

  10. ADVANCED TOOLS FOR ASSESSING SELECTED PRESCRIPTION AND ILLICIT DRUGS IN TREATED SEWAGE EFFLUENTS AND SOURCE WATERS

    EPA Science Inventory

    The purpose of this poster is to present the application and assessment of advanced state-of-the-art technologies in a real-world environment - wastewater effluent and source waters - for detecting six drugs [azithromycin, fluoxetine, omeprazole, levothyroxine, methamphetamine, m...

  11. USE OF CASE REPORTS IN ASSESSING ADVERSE OUTCOMES OF HUMAN PRENATAL DRUG EXPOSURES: AN APPROACH

    EPA Science Inventory

    The use of case reports for assessing the developmental consequences of prenatal drug exposure is limited by the inability to determine the incidence of adverse outcomes and by the high likelihood for bias. Yet, because it is impossible to conduct clinical trials for the assessme...

  12. Probabilistic Vulnerability Assessment Based on Power Flow and Voltage Distribution

    SciTech Connect

    Ma, Jian; Huang, Zhenyu; Wong, Pak C.; Ferryman, Thomas A.

    2010-04-30

    Risk assessment of large scale power systems has been an important problem in power system reliability study. Probabilistic technique provides a powerful tool to solve the task. In this paper, we present the results of a study on probabilistic vulnerability assessment on WECC system. Cumulant based expansion method is applied to obtain the probabilistic distribution function (PDF) and cumulative distribution function (CDF) of power flows on transmission lines and voltage. Overall risk index based on the system vulnerability analysis is calculated using the WECC system. The simulation results based on WECC system is used to demonstrate the effectiveness of the method. The methodology can be applied to the risk analysis on large scale power systems.

  13. 78 FR 9701 - Draft Joint Food and Drug Administration/Health Canada Quantitative Assessment of the Risk of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-11

    ...The Food and Drug Administration (FDA or we) is announcing the availability of a draft ``Joint Food and Drug Administration/Health Canada--Sant[eacute] Canada Quantitative Assessment of the Risk of Listeriosis From Soft-Ripened Cheese Consumption in the United States and Canada.'' This draft Quantitative Risk Assessment (the draft QRA) includes an Interpretative Summary, a Technical Report,......

  14. Hepatocyte-based in vitro model for assessment of drug-induced cholestasis

    SciTech Connect

    Chatterjee, Sagnik; Richert, Lysiane; Augustijns, Patrick; Annaert, Pieter

    2014-01-01

    Early detection of drug-induced cholestasis remains a challenge during drug development. We have developed and validated a biorelevant sandwich-cultured hepatocytes- (SCH) based model that can identify compounds causing cholestasis by altering bile acid disposition. Human and rat SCH were exposed (24–48 h) to known cholestatic and/or hepatotoxic compounds, in the presence or in the absence of a concentrated mixture of bile acids (BAs). Urea assay was used to assess (compromised) hepatocyte functionality at the end of the incubations. The cholestatic potential of the compounds was expressed by calculating a drug-induced cholestasis index (DICI), reflecting the relative residual urea formation by hepatocytes co-incubated with BAs and test compound as compared to hepatocytes treated with test compound alone. Compounds with clinical reports of cholestasis, including cyclosporin A, troglitazone, chlorpromazine, bosentan, ticlopidine, ritonavir, and midecamycin showed enhanced toxicity in the presence of BAs (DICI ? 0.8) for at least one of the tested concentrations. In contrast, the in vitro toxicity of compounds causing hepatotoxicity by other mechanisms (including diclofenac, valproic acid, amiodarone and acetaminophen), remained unchanged in the presence of BAs. A safety margin (SM) for drug-induced cholestasis was calculated as the ratio of lowest in vitro concentration for which was DICI ? 0.8, to the reported mean peak therapeutic plasma concentration. SM values obtained in human SCH correlated well with reported % incidence of clinical drug-induced cholestasis, while no correlation was observed in rat SCH. This in vitro model enables early identification of drug candidates causing cholestasis by disturbed BA handling. - Highlights: • Novel in vitro assay to detect drug-induced cholestasis • Rat and human sandwich-cultured hepatocytes (SCH) as in vitro models • Cholestatic compounds sensitize SCH to toxic effects of accumulating bile acids • Drug-induced cholestasis index (DICI) as measure of a drug's cholestatic signature • In vitro findings correlate well with clinical reports on cholestasis.

  15. QTc prolongation assessment in anticancer drug development: clinical and methodological issues

    PubMed Central

    Curigliano, G; Spitaleri, G; de Braud, F; Cardinale, D; Cipolla, C; Civelli, M; Colombo, N; Colombo, A; Locatelli, M; Goldhirsch, A

    2009-01-01

    Cardiac safety assessments are commonly employed in the clinical development of investigational oncology medications. In anti-cancer drug development there has been increasing consideration for the potential of a compound to cause adverse electrocardiographic changes, especially QT interval prolongation, which can be associated with risk of torsades de pointes and sudden death. Irrespective of overt clinical toxicities, QTc assessment can potentially influence decision making at many levels during the conduct of clinical studies, including eligibility for protocol therapy, dose delivery or discontinuation, and analyses of optimal dose for subsequent development. Given the potential for serious and irreversible morbidity from cardiac adverse events, it is understandable that cardiac safety results can have broad impact on study conduct and patient management. The methodologies for risk management of QTc prolongation for non cardiac drugs have been developed out of experiences primarily from drugs used to treat non life-threatening illnesses in a chronic setting such as antibiotics or antihistamines. Extrapolating these approaches to drugs for treating cancer over an acute period may not be appropriate. Few specific guidelines are available for risk management of cardiac safety in the development and use of oncology drugs. In this manuscript, clinical and methodological issues related to QTc prolongation assessment will be reviewed. Discussions about limitations in phase-I design and oncology drug development will be highlighted. Efforts are needed to refine strategies for risk management, avoiding unintended consequences that negatively affect patient access and clinical development of promising new cancer treatments. A thoughtful risk management plan generated by an organized collaboration between oncologists, cardiologists, and regulatory agencies to support a development programme essential for oncology agents with cardiac safety concerns. PMID:22275999

  16. Assessment of drug disposition in the perfused rat brain by statistical moment analysis

    SciTech Connect

    Sakane, T.; Nakatsu, M.; Yamamoto, A.; Hashida, M.; Sezaki, H.; Yamashita, S.; Nadai, T. )

    1991-06-01

    Drug disposition in the brain was investigated by statistical moment analysis using an improved in situ brain perfusion technique. The right cerebral hemisphere of the rat was perfused in situ. The drug and inulin were injected into the right internal carotid artery as a rapid bolus and the venous outflow curve at the posterior facial vein was obtained. The infusion rate was adjusted to minimize the flow of perfusion fluid into the left hemisphere. The obtained disposition parameters were characteristics and considered to reflect the physicochemical properties of each drug. Antipyrine showed a small degree of initial uptake. Therefore, its apparent distribution volume (Vi) and apparent intrinsic clearance (CLint,i) were small. Diazepam showed large degrees of both influx and efflux and, thus, a large Vi. Water showed parameters intermediate between those of antipyrine and those of diazepam. Imipramine, desipramine, and propranolol showed a large CLint,i compared with those of the other drugs. The extraction ratio of propranolol significantly decreased with increasing concentrations of unlabeled propranolol in the perfusion fluid. These findings may be explained partly by the tissue binding of these drugs. In conclusion, the present method is useful for studying drug disposition in the brain.

  17. Clinical and laboratory assessment of the subjective experience of drug craving.

    PubMed

    Rosenberg, Harold

    2009-08-01

    Measures of subjective drug craving - often defined as the experience of an intense or compelling urge or desire - may be used to predict relapse, evaluate psychological and pharmacological treatments, and test theories of addiction and craving. This review summarizes both direct self-report questionnaires and indirect behavioral, physiological and reaction time measures designed to assess craving for alcohol, amphetamines, cocaine, heroin, marijuana, and tobacco. Multi-item questionnaires have typically been based on one of four underlying conceptualizations of addiction or craving (obsessive-compulsive, approach-avoidance, multi-dimensional, intensity-frequency-duration). Most multi-item self-report questionnaires have high internal consistency, correlate significantly with single-item craving ratings, and demonstrate several aspects of construct validity. Proposed indirect or proxy measures of craving include drug dreams, speed of drug consumption, willingness to work for drug access, selection of monetary rewards over drug access, psychophysiological reactivity, and attentional bias to drug cues. These proxy measures of craving are presumed to obviate self-report biases, to be less subject to conscious self-control, and to reflect craving which the person may not be able to articulate; however, there have been too few demonstrations of their validity and they have too many practical limitations to supplant self-report measures of craving at this time. PMID:19577831

  18. Developing and evaluating distributions for probabilistic human exposure assessments

    SciTech Connect

    Maddalena, Randy L.; McKone, Thomas E.

    2002-08-01

    This report describes research carried out at the Lawrence Berkeley National Laboratory (LBNL) to assist the U. S. Environmental Protection Agency (EPA) in developing a consistent yet flexible approach for evaluating the inputs to probabilistic risk assessments. The U.S. EPA Office of Emergency and Remedial Response (OERR) recently released Volume 3 Part A of Risk Assessment Guidance for Superfund (RAGS), as an update to the existing two-volume set of RAGS. The update provides policy and technical guidance on performing probabilistic risk assessment (PRA). Consequently, EPA risk managers and decision-makers need to review and evaluate the adequacy of PRAs for supporting regulatory decisions. A critical part of evaluating a PRA is the problem of evaluating or judging the adequacy of input distributions PRA. Although the overarching theme of this report is the need to improve the ease and consistency of the regulatory review process, the specific objectives are presented in two parts. The objective of Part 1 is to develop a consistent yet flexible process for evaluating distributions in a PRA by identifying the critical attributes of an exposure factor distribution and discussing how these attributes relate to the task-specific adequacy of the input. This objective is carried out with emphasis on the perspective of a risk manager or decision-maker. The proposed evaluation procedure provides consistency to the review process without a loss of flexibility. As a result, the approach described in Part 1 provides an opportunity to apply a single review framework for all EPA regions and yet provide the regional risk manager with the flexibility to deal with site- and case-specific issues in the PRA process. However, as the number of inputs to a PRA increases, so does the complexity of the process for calculating, communicating and managing risk. As a result, there is increasing effort required of both the risk professionals performing the analysis and the risk manager reviewing it. For deterministic risk assessments, the use of default inputs has improved the ease and the consistency of both performing and reviewing assessments. By analogy, it is expected that similar advantage will be seen in the field of probabilistic risk assessment through the introduction of default distributions. In Part 2 of this report, we consider when a default distribution might be appropriate for use in PRA and work towards development of recommended task-specific distributions for several frequently used exposure factors. An approach that we develop using body weight and exposure duration as case studies offers a transparent way for developing task-specific exposure factor distributions. A third case study using water intake highlights the need for further study aimed at improving the relevance of ''short-term'' data before recommendations on task-specific distributions of water intake can be made.

  19. Population data analysis of dissolution time profiles: Assessment of physicochemical properties of the drug, drug particles and the pharmaceutical formulation.

    PubMed

    Horkovics-Kovats, Stefan; Brunovský, Pavel; Pichler, Arthur; Bulitta, Jürgen B

    2015-10-12

    Disintegration of finished dosage forms (FDF) and drug dissolution are fundamentally important processes that affect bioavailability. Established theories do not account for disintegration and usually assume sink conditions for drug dissolution that often do not apply. We present the theory to describe the disintegration of FDF with subsequent dissolution of liberated particles containing the active pharmaceutical ingredient (API) and its application using population data analysis. Population modeling, using dissolution profiles of 400mg cefditoren pivoxil tablets manufactured under various tableting pressures, characterized the intrinsic lifetime distribution of the particles and identified the presence of crystalline API in the formulation that was proven by X-ray diffraction. Modeling further estimated the disintegration time of FDF, the solubility of the amorphous API and its chemical instability in the medium that were in agreement with the experimentally determined values. This novel approach provides a quantitative understanding of the manufacturing process of FDF and can substantially contribute to the targeted development of finished dosage forms. PMID:26215465

  20. Communication Needs Assessment for Distributed Turbine Engine Control

    NASA Technical Reports Server (NTRS)

    Culley, Dennis E.; Behbahani, Alireza R.

    2008-01-01

    Control system architecture is a major contributor to future propulsion engine performance enhancement and life cycle cost reduction. The control system architecture can be a means to effect net weight reduction in future engine systems, provide a streamlined approach to system design and implementation, and enable new opportunities for performance optimization and increased awareness about system health. The transition from a centralized, point-to-point analog control topology to a modular, networked, distributed system is paramount to extracting these system improvements. However, distributed engine control systems are only possible through the successful design and implementation of a suitable communication system. In a networked system, understanding the data flow between control elements is a fundamental requirement for specifying the communication architecture which, itself, is dependent on the functional capability of electronics in the engine environment. This paper presents an assessment of the communication needs for distributed control using strawman designs and relates how system design decisions relate to overall goals as we progress from the baseline centralized architecture, through partially distributed and fully distributed control systems.

  1. In silico assessment of drug safety in human heart applied to late sodium current blockers

    PubMed Central

    Trenor, Beatriz; Gomis-Tena, Julio; Cardona, Karen; Romero, Lucia; Rajamani, Sridharan; Belardinelli, Luiz; Giles, Wayne R; Saiz, Javier

    2013-01-01

    Drug-induced action potential (AP) prolongation leading to Torsade de Pointes is a major concern for the development of anti-arrhythmic drugs. Nevertheless the development of improved anti-arrhythmic agents, some of which may block different channels, remains an important opportunity. Partial block of the late sodium current (INaL) has emerged as a novel anti-arrhythmic mechanism. It can be effective in the settings of free radical challenge or hypoxia. In addition, this approach can attenuate pro-arrhythmic effects of blocking the rapid delayed rectifying K+ current (IKr). The main goal of our computational work was to develop an in-silico tool for preclinical anti-arrhythmic drug safety assessment, by illustrating the impact of IKr/INaL ratio of steady-state block of drug candidates on “torsadogenic” biomarkers. The O’Hara et al. AP model for human ventricular myocytes was used. Biomarkers for arrhythmic risk, i.e., AP duration, triangulation, reverse rate-dependence, transmural dispersion of repolarization and electrocardiogram QT intervals, were calculated using single myocyte and one-dimensional strand simulations. Predetermined amounts of block of INaL and IKr were evaluated. “Safety plots” were developed to illustrate the value of the specific biomarker for selected combinations of IC50s for IKr and INaL of potential drugs. The reference biomarkers at baseline changed depending on the “drug” specificity for these two ion channel targets. Ranolazine and GS967 (a novel potent inhibitor of INaL) yielded a biomarker data set that is considered safe by standard regulatory criteria. This novel in-silico approach is useful for evaluating pro-arrhythmic potential of drugs and drug candidates in the human ventricle. PMID:23696033

  2. New investigation of distribution imaging and content uniformity of very low dose drugs using hot-melt extrusion method.

    PubMed

    Park, Jun-Bom; Kang, Chin-Yang; Kang, Wie-Soo; Choi, Han-Gon; Han, Hyo-Kyung; Lee, Beom-Jin

    2013-12-31

    The content uniformity of low dose drugs in dosage forms is very important for quality assurance. The aim of this study was to prepare uniformly and homogeneously distributed dosage forms of very low-dose drugs using twin screw hot-melt extrusion (HME) and to investigate the distribution of drugs using instrumental analyses. For the feasibility of HME method, a very low amount of coumarin-6, a fluorescent dye, was used to visualize distribution images using confocal laser scanning microscope (CLSM). Limaprost, tamsulosin and glimepiride were then used as low-dose model drugs to study the applicability of HME for content uniformity and distribution behaviors. Hydrophilic thermosensitive polymers with low melting point, such as Poloxamer188 and polyethylene glycol (PEG) 6000, were chosen as carriers. The melt extrusion was carried out around 50°C, at which both carriers were easily dissolved but model drugs remained in solid form. The physicochemical properties of the hot-melt extrudates, including differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR), were measured. Content uniformity of the drugs was also checked by HPLC. CLSM imaging showed that model drugs were well distributed throughout the hot-melt extrudate, giving better content uniformity with low batch-to-batch variations compared with simple physical mixtures. DSC, PXRD and FT-IR data showed that there was no interaction or interference between model drugs and thermosensitive polymers. The current HME methods could be used to prepare uniformly distributed and reproducible solid dosage forms containing very low dose drugs for further pharmaceutical applications. PMID:24157343

  3. Cold Air Distribution in Office Buildings: Technology Assessment for California

    SciTech Connect

    Bauman, F.S.; Borgers, T.; LaBerge, P.; Gadgil, A.J.

    1992-06-01

    This paper presents the results of a study to assess the current state of practice, and energy and operating cost implications of cold air distribution in California, and to identify the key research needs for the continued development of this technology in new commercial buildings in the state. Whole-building energy simulations were made to compare the energy performance of a prototypical office building in three California climates using conventional and cold air distribution, with and without ice storage, to show the impacts of load shifting, energy use, and utility costs for three typical utility rate structures. The merits of economizers and fan-powered mixing boxes were also studied when used in conjunction with cold air delivery. A survey was conducted to assess the perceived strengths and limitations of this technology, perceived barriers to its widespread use, and user experience. The survey was based on interviews with consulting engineers, equipment manufacturers, researchers, utility representatives, and other users of cold air distribution technology. Selected findings from the industry survey are also discussed. Cold air distribution (CoAD) is found to always reduce fan energy use in comparison to conventional 55 F (13 C) air distribution systems, when conditioned air is delivered directly to the space (no fan-powered mixing boxes). Total building energy use for ice storage/CoAD systems was always higher than a well-designed conventional system, but significantly lower than a commonly-installed packaged system. When a favorable utility rate structure was applied, the load-shifting benefits of ice storage/CoAD systems produced the lowest annual operating costs of all system-plant configurations studied.

  4. Cold air distribution in office buildings: Technology assessment for California

    SciTech Connect

    Bauman, F.S.; LaBege, P. . Center for Environmental Design Research); Borgers, T. . Dept. of Chemistry); Gadgil, A.J. )

    1992-06-01

    This paper presents the results of a study to assess the current state of practice, and energy and operating cost implications of cold air distribution in California, and to identify the key research needs for the continued development of this technology in new commercial buildings in the state. Whole-building energy simulations were made to compare the energy performance of a prototypical office building in three California climates using conventional and cold air distribution, with and without ice storage, to show the impacts of load shifting, energy use, and utility costs for three typical utility rate structures. The merits of economizers and fan-powered mixing boxes were also studied when used in conjunction with cold air delivery. A survey was conducted to assess the perceived strengths and limitations of this technology, perceived barriers to its widespread use, and user experience. The survey was based on interviews with consulting engineers, equipment manufacturers, researchers, utility representatives, and other users of cold air distribution technology. Selected findings from the industry survey are also discussed. Cold air distribution (CoAD) is found to always reduce fan energy use in comparison to conventional 55[degrees]F (13[degrees]C) air distribution systems, when conditioned air is delivered directly to the space (no fan-powered mixing boxes). Total building energy use for ice storage/CoAD systems was always higher than a well-designed conventional system, but significantly lower than a commonly-installed packaged system. When a favorable utility rate structure was applied, the load-shifting benefits of ice storage/CoAD systems produced the lowest annual operating costs of all system-plant configurations studied.

  5. Life cycle assessment of overhead and underground primary power distribution.

    PubMed

    Bumby, Sarah; Druzhinina, Ekaterina; Feraldi, Rebe; Werthmann, Danae; Geyer, Roland; Sahl, Jack

    2010-07-15

    Electrical power can be distributed in overhead or underground systems, both of which generate a variety of environmental impacts at all stages of their life cycles. While there is considerable literature discussing the trade-offs between both systems in terms of aesthetics, safety, cost, and reliability, environmental assessments are relatively rare and limited to power cable production and end-of-life management. This paper assesses environmental impacts from overhead and underground medium voltage power distribution systems as they are currently built and managed by Southern California Edison (SCE). It uses process-based life cycle assessment (LCA) according to ISO 14044 (2006) and SCE-specific primary data to the extent possible. Potential environmental impacts have been calculated using a wide range of midpoint indicators, and robustness of the results has been investigated through sensitivity analysis of the most uncertain and potentially significant parameters. The studied underground system has higher environmental impacts in all indicators and for all parameter values, mostly due to its higher material intensity. For both systems and all indicators the majority of impact occurs during cable production. Promising strategies for impact reduction are thus cable failure rate reduction for overhead and cable lifetime extension for underground systems. PMID:20553042

  6. A community effort to assess and improve drug sensitivity prediction algorithms.

    PubMed

    Costello, James C; Heiser, Laura M; Georgii, Elisabeth; Gönen, Mehmet; Menden, Michael P; Wang, Nicholas J; Bansal, Mukesh; Ammad-ud-din, Muhammad; Hintsanen, Petteri; Khan, Suleiman A; Mpindi, John-Patrick; Kallioniemi, Olli; Honkela, Antti; Aittokallio, Tero; Wennerberg, Krister; Collins, James J; Gallahan, Dan; Singer, Dinah; Saez-Rodriguez, Julio; Kaski, Samuel; Gray, Joe W; Stolovitzky, Gustavo

    2014-12-01

    Predicting the best treatment strategy from genomic information is a core goal of precision medicine. Here we focus on predicting drug response based on a cohort of genomic, epigenomic and proteomic profiling data sets measured in human breast cancer cell lines. Through a collaborative effort between the National Cancer Institute (NCI) and the Dialogue on Reverse Engineering Assessment and Methods (DREAM) project, we analyzed a total of 44 drug sensitivity prediction algorithms. The top-performing approaches modeled nonlinear relationships and incorporated biological pathway information. We found that gene expression microarrays consistently provided the best predictive power of the individual profiling data sets; however, performance was increased by including multiple, independent data sets. We discuss the innovations underlying the top-performing methodology, Bayesian multitask MKL, and we provide detailed descriptions of all methods. This study establishes benchmarks for drug sensitivity prediction and identifies approaches that can be leveraged for the development of new methods. PMID:24880487

  7. Assessment of tailor-made HPMC-based matrix minitablets comprising a weakly basic drug compound.

    PubMed

    Siepe, Stefanie; Lueckel, Barbara; Kramer, Andrea; Ries, Angelika; Gurny, Robert

    2008-01-01

    Tailor-made, pH-controlled matrix minitablets based on different HPMC types were developed comprising the weakly basic drug dipyridamole. The incorporation of pH modifiers, i.e., fumaric and succinic acid, enhanced the drug release at pH 6.8. Assessing the drug release, acid release, and the microenvironmental pH (pHM) provided detailed understanding of pH-controlled mini-matrices. The extent and duration of pHM alteration was more pronounced in presence of fumaric acid. Minitablets based on the fast dissolving Methocel K100LV (< or = 100 cps) showed simultaneous release rates of dipyridamole and fumaric acid with a constant low average pHM. PMID:18214754

  8. Laser-evoked potentials as a tool for assessing the efficacy of antinociceptive drugs.

    PubMed

    Truini, A; Panuccio, G; Galeotti, F; Maluccio, M R; Sartucci, F; Avoli, M; Cruccu, G

    2010-02-01

    Laser-evoked potentials (LEPs) are brain responses to laser radiant heat pulses and reflect the activation of Adelta nociceptors. LEPs are to date the reference standard technique for studying nociceptive pathway function in patients with neuropathic pain. To find out whether LEPs also provide a useful neurophysiological tool for assessing antinociceptive drug efficacy, in this double-blind placebo-controlled study we measured changes induced by the analgesic tramadol on LEPs in 12 healthy subjects. We found that tramadol decreased the amplitude of LEPs, whereas placebo left LEPs unchanged. The opioid antagonist naloxone partially reversed the tramadol-induced LEP amplitude decrease. We conclude that LEPs may be reliably used in clinical practice and research for assessing the efficacy of antinociceptive drugs. PMID:19477145

  9. AN ASSESSMENT OF WOOD DUCK DISTRIBUTION, ABUNDANCE AND RIPARIAN BREEDING PAIR HABITATS IN SOUTH DAKOTA

    E-print Network

    AN ASSESSMENT OF WOOD DUCK DISTRIBUTION, ABUNDANCE AND RIPARIAN BREEDING PAIR HABITATS IN SOUTH #12;AN ASSESSMENT OF WOOD DUCK DISTRIBUTION, ABUNDANCE AND RIPARIAN BREEDING PAIR HABITATS IN SOUTH Wildlife and Fisheries Sciences #12;AN ASSESSMENT OF WOOD DUCK DISTRIBUTION, ABUNDANCE AND RIPARIAN

  10. Digital technologies for cognitive assessment to accelerate drug development in Alzheimer's disease.

    PubMed

    Leurent, C; Ehlers, M D

    2015-11-01

    For many neurological and psychiatric diseases, novel therapeutics have been elusive for decades. By focusing on attention interference in Alzheimer's disease (AD), we provide a future vision on how emerging mobile, computer, and device-based cognitive tools are converting classically noisy, subjective, data-poor clinical endpoints associated with neuropsychiatric disease assessment into a richer, scalable, and objective set of measurements. Incorporation of such endpoints into clinical drug trials holds promise for more quickly and efficiently developing new medicines. PMID:26272508

  11. Raman and infrared techniques for fighting drug-related crime: a preliminary assessment

    NASA Astrophysics Data System (ADS)

    Valussi, Silvia; Underhill, Mark

    2006-09-01

    A proof-of-concept hand-held Raman spectrometer and a commercial portable system based on Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) were assessed for the rapid, "at scene" analysis of illicit drugs. The objectives of such an assessment were twofold: 1) to determine the suitability of the systems in practical forensic casework and 2) to determine the potential of the use of such systems in covert operations. Data obtained are promising and demonstrate the potential advantages and limitations of the use of these techniques in these fields of operation.

  12. Anti-angiogenesis or pro-angiogenesis for cancer treatment: focus on drug distribution

    PubMed Central

    Huang, Dongsheng; Lan, Huanrong; Liu, Fanlong; Wang, Shibing; Chen, Xiaoyi; Jin, Ketao; Mou, Xiaozhou

    2015-01-01

    Enhancing chemotherapy delivery to tumors, improving tumor growth control, reducing metastasis, and increasing survival are all critical objectives of improved cancer therapy. One of the obstacles to the success of anticancer therapies is related to the inefficient distribution of drugs to tumor cells. To be effective, chemotherapeutics must reach a concentration in cancer cells that is sufficient to inhibit its targets. In the past years, the vascular normalization theory has gained widespread acceptance for explaining additional antitumor effects of inhibitors of vascular endothelial growth factor (VEGF) signaling, when combined with chemotherapeutics. Vascular normalization is a strategy to enhance the antitumor effects of chemotherapeutics, but this is time and dose dependent and therefore difficult to implement clinically. Thus, alternative strategies that overcome these issues are needed. Accumulating scientific data demonstrate an alternative approach called “vascular promotion therapy” can increase chemotherapeutics delivery and intracellular uptake of the drug and reduces hypoxia by increasing tumor blood vessel density, blood flow, leakiness, and dilation, which leads to reduced cancer growth and metastasis. In this article, we first summarize the structural and functional abnormalities of the tumor microvasculature to highlight the importance of this phenomenon for chemotherapeutics distribution. Next, we summarize the limitations of anti-angiogenic strategy in cancer treatment, discuss some key prototypical underlying mechanisms of vascular normalization and initial clinical evidence of vascular promotion therapy, and speculate on the clinical potential of anticoagulation as a novel paradigm to improve cancer treatment. PMID:26309490

  13. Trends in HCV prevalence, risk factors and distribution of viral genotypes in injecting drug users: findings from two cross-sectional studies.

    PubMed

    Oliveira, M L A; Yoshida, C F T; Telles, P R; Hacker, M A; Oliveira, S A N; Miguel, J C; do O, K M R; Bastos, F I

    2009-07-01

    In the last decade, a declining prevalence of HCV infection has been described in injecting drug users (IDUs) in different countries. This study is the first to assess temporal trends in drug-injecting patterns, HCV infection rates and viral genotype distribution in 770 Brazilian IDUs, recruited by two cross-sectional studies (1994-1997 and 1999-2001). A substantial decline in the prevalence of HCV infection was found over the years (75% in 1994 vs. 20.6% in 2001, P<0.001) that may be a consequence of the significant reduction in the overall frequencies of drug injection and needle-sharing, as well as the participation of IDUs in initiatives aimed at reducing drug-related harm. No trend was found in terms of viral genotype distribution. Despite the favourable scenario, preventive measures must be maintained, especially in vulnerable subgroups such as young or new injectors, where risky behaviours through direct and indirect sharing practices remain common. PMID:19144250

  14. Microbial degradation of illicit drugs, their precursors, and manufacturing by-products: implications for clandestine drug laboratory investigation and environmental assessment.

    PubMed

    Janusz, A; Kirkbride, K P; Scott, T L; Naidu, R; Perkins, M V; Megharaj, M

    2003-06-24

    Chemicals associated with clandestine drug laboratories are often disposed of covertly into soil, sewerage systems, or public waste management facilities. There are two significant issues relating to such dumps of materials; they might contain valuable evidence as to drug manufacture, and they might be a source of pollution. This study presents initial findings in relation to the impact microorganisms from environmental sources have upon drugs, their precursors, and manufacturing by-products. The aim of this study was to identify which chemicals associated with clandestine drug laboratories persist in the environment in order to allow forensic drug chemists to link discarded residues with the method of manufacture, and to allow the environmental impact of clandestine drug laboratories to be assessed accurately. When exposed to soil microorganisms, phenyl-2-propanone (P2P) was rapidly metabolized into mixtures of 1-phenyl-2-propanol, 1-phenyl-1,2-propanedione, 1-hydroxy-1-phenyl-2-propanone, 2-hydroxy-1-phenyl-1-propanone, and the two diastereoisomers of 1-phenyl-1,2-propanediol. On the other hand, when exposed under the same conditions, methylamphetamine sulphate (MAS) remained virtually unchanged. Implications relating to evidence gathering for forensic purposes and to environmental assessment of clandestine drug laboratories are discussed. PMID:12842360

  15. Parental and offspring assessment of driving capability under the influence of drugs or alcohol: gender and inter-generational differences.

    PubMed

    Rosenbloom, Tova; Beigel, Ariela; Perlman, Amotz; Eldror, Ehud

    2010-11-01

    The current study set to examine whether there are inter-generational and gender-based differences between family members self-assessing their ability to drive under normal conditions and while under the influence of either alcohol or drugs. Participants were 135 young-adults and both their parents, consisting 45 family triads, who received self-assessment questionnaires relating to their driving skills in various road scenarios. Each family triad was randomly assigned to one of three groups: either requested to base the assessments on normal driving conditions, or under the influence of either drugs or alcohol, thus forming a control group, and two experimental groups (alcohol and drugs), respectively. The findings indicate the assessments of both the alcohol and drugs groups were more severe than those of the control group. The alcohol group assessments were less strict than the drug group assessment (non-significantly). Inter-generational differences indicated that the parents' driving-skills assessments were lower than those of their offspring, corresponding with previous findings (Elkind, 1967; Finn and Bragg, 1986). A significant within-subject interaction has been found between the respondent's gender and familial relations regarding the self-assessment of driving skills: male respondents assessed better driving skills compared to the self estimates of both parents (which did not significantly differ). In contrast, female respondents' estimates did not differ from their fathers' and both fathers' and daughters' estimates were significantly higher than that of the mothers in each family. PMID:20728671

  16. Assessment of temperature-induced hERG channel blockade variation by drugs.

    PubMed

    Kauthale, Rahul R; Dadarkar, Shruta S; Husain, Raghib; Karande, Vikas V; Gatne, Madhumanjiri M

    2015-07-01

    Drug-induced QT prolongation has been reported in humans and animals. This potentially lethal effect can be induced by drugs interacting with a cardiac potassium channel, namely hERG (human ether-a go-go-related gene) leading to arrhythmia or torsade de pointes (TdP). Hence, in vitro evaluation of therapeutics for their effects on the rapid delayed rectifier current (IKr) mediated by the K(+) ion channel encoded by hERG is a valuable tool for identifying potential arrhythmic side effects during drug safety testing. Our objective was to evaluate the temperature-induced hERG channel blockade variation by human and veterinary drugs using the IonFlux 16 system. A panel of eight drugs was tested for IKr inhibition at both ambient (23?°C) and physiological (37?°C) temperatures at various concentrations using IonFlux 16, an automated patch clamp system. Our results established that both amiodarone (IC(50) ?=?0.56??M at 23?°C and 0.30??M at 37?°C) and ?-estradiol (IC(50) ?=?24.72??M at 23?°C and 8.17??M at 37?°C) showed a dose-dependent IKr blockade with a higher blockade at 37?°C. Whereas, blockade of IKr by both ivermectin (IC(50) ?=?12.52??M at 23?°C and 24.41??M at 37?°C) and frusemide (IC(50) ?=?12.58??M at 23?°C and 25.55??M at 37?°C) showed a dose-dependent IKr blockade with a lower blockade at 37?°C. Gentamicin, enrofloxacin, xylazine and albendazole did not block IKr at both the assessed temperatures. Collectively, these results demonstrate that the effect of temperature variation should be taken into consideration during the evaluation of test drugs for their hERG channel blockade potential. PMID:25348819

  17. Myocardial drug distribution generated from local epicardial application: potential impact of cardiac capillary perfusion in a swine model using epinephrine.

    PubMed

    Maslov, Mikhail Y; Edelman, Elazer R; Pezone, Matthew J; Wei, Abraham E; Wakim, Matthew G; Murray, Michael R; Tsukada, Hisashi; Gerogiannis, Iraklis S; Groothuis, Adam; Lovich, Mark A

    2014-11-28

    Prior studies in small mammals have shown that local epicardial application of inotropic compounds drives myocardial contractility without systemic side effects. Myocardial capillary blood flow, however, may be more significant in larger species than in small animals. We hypothesized that bulk perfusion in capillary beds of the large mammalian heart not only enhances drug distribution after local release, but also clears more drug from the tissue target than in small animals. Epicardial (EC) drug releasing systems were used to apply epinephrine to the anterior surface of the left heart of swine in either point-sourced or distributed configurations. Following local application or intravenous (IV) infusion at the same dose rates, hemodynamic responses, epinephrine levels in the coronary sinus and systemic circulation, and drug deposition across the ventricular wall, around the circumference and down the axis, were measured. EC delivery via point-source release generated transmural epinephrine gradients directly beneath the site of application extending into the middle third of the myocardial thickness. Gradients in drug deposition were also observed down the length of the heart and around the circumference toward the lateral wall, but not the interventricular septum. These gradients extended further than might be predicted from simple diffusion. The circumferential distribution following local epinephrine delivery from a distributed source to the entire anterior wall drove drug toward the inferior wall, further than with point-source release, but again, not to the septum. This augmented drug distribution away from the release source, down the axis of the left ventricle, and selectively toward the left heart follows the direction of capillary perfusion away from the anterior descending and circumflex arteries, suggesting a role for the coronary circulation in determining local drug deposition and clearance. The dominant role of the coronary vasculature is further suggested by the elevated drug levels in the coronary sinus effluent. Indeed, plasma levels, hemodynamic responses, and myocardial deposition remote from the point of release were similar following local EC or IV delivery. Therefore, the coronary vasculature shapes the pharmacokinetics of local myocardial delivery of small catecholamine drugs in large animal models. Optimal design of epicardial drug delivery systems must consider the underlying bulk capillary perfusion currents within the tissue to deliver drug to tissue targets and may favor therapeutic molecules with better potential retention in myocardial tissue. PMID:25234821

  18. Myocardial Drug Distribution Generated from Local Epicardial Application: Potential Impact of Cardiac Capillary Perfusion in a Swine Model Using Epinephrine

    PubMed Central

    Maslov, Mikhail Y.; Edelman, Elazer R.; Pezone, Matthew J.; Wei, Abraham E.; Wakim, Matthew G.; Murray, Michael R.; Tsukada, Hisashi; Gerogiannis, Iraklis S.; Groothuis, Adam; Lovich, Mark A.

    2014-01-01

    Prior studies in small mammals have shown that local epicardial application of inotropic compounds drives myocardial contractility without systemic side effects. Myocardial capillary blood flow, however, may be more significant in larger species than in small animals. We hypothesized that bulk perfusion in capillary beds of the large mammalian heart enhances drug distribution after local release, but also clears more drug from the tissue target than in small animals. Epicardial (EC) drug releasing systems were used to apply epinephrine to the anterior surface of the left heart of swine in either point-sourced or distributed configurations. Following local application or intravenous (IV) infusion at the same dose rates, hemodynamic responses, epinephrine levels in the coronary sinus and systemic circulation, and drug deposition across the ventricular wall, around the circumference and down the axis, were measured. EC delivery via point-source release generated transmural epinephrine gradients directly beneath the site of application extending into the middle third of the myocardial thickness. Gradients in drug deposition were also observed down the length of the heart and around the circumference toward the lateral wall, but not the interventricular septum. These gradients extended further than might be predicted from simple diffusion. The circumferential distribution following local epinephrine delivery from a distributed source to the entire anterior wall drove drug toward the inferior wall, further than with point-source release, but again, not to the septum. This augmented drug distribution away from the release source, down the axis of the left ventricle, and selectively towards the left heart follows the direction of capillary perfusion away from the anterior descending and circumflex arteries, suggesting a role for the coronary circulation in determining local drug deposition and clearance. The dominant role of the coronary vasculature is further suggested by the elevated drug levels in the coronary sinus effluent. Indeed, plasma levels, hemodynamic responses, and myocardial deposition remote from the point of release were similar following local EC or IV delivery. Therefore, the coronary vasculature shapes the pharmacokinetics of local myocardial delivery of small catecholamine drugs in large animal models. Optimal design of epicardial drug delivery systems must consider the underlying bulk capillary perfusion currents within the tissue to deliver drug to tissue targets and may favor therapeutic molecules with better potential retention in myocardial tissue. PMID:25234821

  19. Are zebrafish larvae suitable for assessing the hepatotoxicity potential of drug candidates?

    PubMed

    Mesens, Natalie; Crawford, Alexander D; Menke, Aswin; Hung, Pham Duc; Van Goethem, Freddy; Nuyts, Rik; Hansen, Erik; Wolterbeek, Andre; Van Gompel, Jacky; De Witte, Peter; Esguerra, Camila V

    2015-09-01

    Drug-induced liver injury (DILI) is poorly predicted by single-cell-based assays, probably because of the lack of physiological interactions with other cells within the liver. An intact whole liver system such as one present in zebrafish larvae could provide added value in a screening strategy for DILI; however, the possible occurrence of other organ toxicities and the immature larval stage of the zebrafish might complicate accurate and fast analysis. We investigated whether expression analysis of liver-specific fatty acid binding protein 10a (lfabp10a) was an appropriate endpoint for assessing hepatotoxic effects in zebrafish larvae. It was found that expression analysis of lfabp10a was a valid marker, as after treatment with hepatotoxicants, dose-response curves could be obtained and statistically significant abnormal lfabp10 expression levels correlated with hepatocellular histopathological changes in the liver. However, toxicity in other vital organs such as the heart could impact liver outgrowth and thus had to be assessed concurrently. Whether zebrafish larvae were suitable for assessing human relevant drug-induced hepatotoxicity was assessed with hepatotoxicants and non-hepatotoxicants that have been marketed for human use and classified according to their mechanism of toxicity. The zebrafish larva showed promising predictivity towards a number of mechanisms and was capable of distinguishing between hepatotoxic and non-hepatotoxic chemical analogues, thus implying its applicability as a potential screening model for DILI. PMID:25663337

  20. The practice of pre-marketing safety assessment in drug development.

    PubMed

    Chuang-Stein, Christy; Xia, H Amy

    2013-01-01

    The last 15 years have seen a substantial increase in efforts devoted to safety assessment by statisticians in the pharmaceutical industry. While some of these efforts were driven by regulations and public demand for safer products, much of the motivation came from the realization that there is a strong need for a systematic approach to safety planning, evaluation, and reporting at the program level throughout the drug development life cycle. An efficient process can help us identify safety signals early and afford us the opportunity to develop effective risk minimization plan early in the development cycle. This awareness has led many pharmaceutical sponsors to set up internal systems and structures to effectively conduct safety assessment at all levels (patient, study, and program). In addition to process, tools have emerged that are designed to enhance data review and pattern recognition. In this paper, we describe advancements in the practice of safety assessment during the premarketing phase of drug development. In particular, we share examples of safety assessment practice at our respective companies, some of which are based on recommendations from industry-initiated working groups on best practice in recent years. PMID:23331218

  1. Analysis of Diffusion-Controlled Dissolution from Polydisperse Collections of Drug Particles with an Assessed Mathematical Model.

    PubMed

    Wang, Yanxing; Abrahamsson, Bertil; Lindfors, Lennart; Brasseur, James G

    2015-09-01

    We introduce a "hierarchical" modeling strategy designed to be systematically extensible to increase the detail of dissolution predictions from polydisperse collections of drug particles and to be placed on firm mathematical and physical foundations with diffusion-dominated dissolution at its core to predict dissolution and the evolution of particle size distribution. We assess the model with experimental data and demonstrate higher accuracy by treating the polydisperse nature of dissolution. A level in the hierarchy is applied to study elements of diffusion-driven dissolution, in particular the role of particle-size distribution width with varying dose level and the influences of "confinement" on the process of dissolution. Confinement influences surface molecular flux, directly by the increase in bulk concentration and indirectly by the relative volume of particles to container. We find that the dissolution process can be broadly categorized within three "regimes" defined by the ratio of total concentration Ctot to solubility CS . Sink conditions apply in the first regime, when C tot /CS?5 (regime 3) dissolution is dominated by confinement and normalized saturation time follows a simple power law relationship. Regime 2 is characterized by a "saturation singularity" where dissolution is sensitive to both initial particle size distribution and confinement. PMID:25989144

  2. Understanding the Assessment of Psychotropic Drug Harms in Clinical Trials to Improve Social Workers' Role in Medication Monitoring

    ERIC Educational Resources Information Center

    Hughes, Shannon; Cohen, David

    2010-01-01

    The purpose of this integrative review is to facilitate social work practitioners' understanding of how psychotropic drug harms are assessed in clinical trials and to make specific suggestions for social workers' increased involvement in detecting drug harms in their clients. The authors undertook a comprehensive review of interdisciplinary…

  3. Assessing a Tornado Climatology from Global Tornado Intensity Distributions.

    NASA Astrophysics Data System (ADS)

    Feuerstein, Bernold; Dotzek, Nikolai; Grieser, Jürgen

    2005-02-01

    Recent work demonstrated that the shape of tornado intensity distributions from various regions worldwide is well described by Weibull functions. This statistical modeling revealed a strong correlation between the fit parameters c for shape and b for scale regardless of the data source. In the present work it is shown that the quality of the Weibull fits is optimized if only tornado reports of F1 and higher intensity are used and that the c-b correlation does indeed reflect a universal feature of the observed tornado intensity distributions. For regions with likely supercell tornado dominance, this feature is the number ratio of F4 to F3 tornado reports R(F4/F3) = 0.238. The c-b diagram for the Weibull shape and scale parameters is used as a climatological chart, which allows different types of tornado climatology to be distinguished, presumably arising from supercell versus nonsupercell tornadogenesis. Assuming temporal invariance of the climatology and using a detection efficiency function for tornado observations, a stationary climatological probability distribution from large tornado records (U.S. decadal data 1950-99) is extracted. This can be used for risk assessment, comparative studies on tornado intensity distributions worldwide, and estimates of the degree of underreporting for areas with poor databases. For the 1990s U.S. data, a likely tornado underreporting of the weak events (F0, F1) by a factor of 2 can be diagnosed, as well as asymptotic climatological c,b values of c = 1.79 and b = 2.13, to which a convergence in the 1950-99 U.S. decadal data is verified.

  4. Role of transporters in the distribution of platinum-based drugs

    PubMed Central

    Harrach, Saliha; Ciarimboli, Giuliano

    2015-01-01

    Platinum derivatives used as chemotherapeutic drugs such as cisplatin and oxaliplatin have a potent antitumor activity. However, severe side effects such as nephro-, oto-, and neurotoxicity are associated with their use. Effects and side effects of platinum-based drugs are in part caused by their transporter-mediated uptake in target and non target cells. In this mini review, the transport systems involved in cellular handling of platinum derivatives are illustrated, focusing on transporters for cisplatin. The copper transporter 1 seems to be of particular importance for cisplatin uptake in tumor cells, while the organic cation transporter (OCT) 2, due to its specific organ distribution, may play a major role in the development of undesired cisplatin side effects. In polarized cells, e.g., in renal proximal tubule cells, apically expressed transporters, such as multidrug and toxin extrusion protein 1, mediate secretion of cisplatin and in this way contribute to the control of its toxic effects. Specific inhibition of cisplatin uptake transporters such as the OCTs may be an attractive therapeutic option to reduce its toxicity, without impairing its antitumor efficacy. PMID:25964760

  5. Assessing the HIV-1 Epidemic in Brazilian Drug Users: A Molecular Epidemiology Approach.

    PubMed

    Guimarães, Monick Lindenmeyer; Marques, Bianca Cristina Leires; Bertoni, Neilane; Teixeira, Sylvia Lopes Maia; Morgado, Mariza Gonçalves; Bastos, Francisco Inácio

    2015-01-01

    Person who inject illicit substances have an important role in HIV-1 blood and sexual transmission and together with person who uses heavy non-injecting drugs may have less than optimal adherence to anti-retroviral treatment and eventually could transmit resistant HIV variants. Unfortunately, molecular biology data on such key population remain fragmentary in most low and middle-income countries. The aim of the present study was to assess HIV infection rates, evaluate HIV-1 genetic diversity, drug resistance, and to identify HIV transmission clusters in heavy drug users (DUs). For this purpose, DUs were recruited in the context of a Respondent-Driven Sampling (RDS) study in different Brazilian cities during 2009. Overall, 2,812 individuals were tested for HIV, and 168 (6%) of them were positive, of which 19 (11.3%) were classified as recent seroconverters, corresponding to an estimated incidence rate of 1.58%/year (95% CI 0.92-2.43%). Neighbor joining phylogenetic trees from env and pol regions and bootscan analyses were employed to subtype the virus from132 HIV-1-infected individuals. HIV-1 subtype B was prevalent in most of the cities under analysis, followed by BF recombinants (9%-35%). HIV-1 subtype C was the most prevalent in Curitiba (46%) and Itajaí (86%) and was also detected in Brasília (9%) and Campo Grande (20%). Pure HIV-1F infections were detected in Rio de Janeiro (9%), Recife (6%), Salvador (6%) and Brasília (9%). Clusters of HIV transmission were assessed by Maximum likelihood analyses and were cross-compared with the RDS network structure. Drug resistance mutations were verified in 12.2% of DUs. Our findings reinforce the importance of the permanent HIV-1 surveillance in distinct Brazilian cities due to viral resistance and increasing subtype heterogeneity all over Brazil, with relevant implications in terms of treatment monitoring, prophylaxis and vaccine development. PMID:26536040

  6. Assessing the HIV-1 Epidemic in Brazilian Drug Users: A Molecular Epidemiology Approach

    PubMed Central

    Guimarães, Monick Lindenmeyer; Marques, Bianca Cristina Leires; Bertoni, Neilane; Teixeira, Sylvia Lopes Maia; Morgado, Mariza Gonçalves; Bastos, Francisco Inácio

    2015-01-01

    Person who inject illicit substances have an important role in HIV-1 blood and sexual transmission and together with person who uses heavy non-injecting drugs may have less than optimal adherence to anti-retroviral treatment and eventually could transmit resistant HIV variants. Unfortunately, molecular biology data on such key population remain fragmentary in most low and middle-income countries. The aim of the present study was to assess HIV infection rates, evaluate HIV-1 genetic diversity, drug resistance, and to identify HIV transmission clusters in heavy drug users (DUs). For this purpose, DUs were recruited in the context of a Respondent-Driven Sampling (RDS) study in different Brazilian cities during 2009. Overall, 2,812 individuals were tested for HIV, and 168 (6%) of them were positive, of which 19 (11.3%) were classified as recent seroconverters, corresponding to an estimated incidence rate of 1.58%/year (95% CI 0.92–2.43%). Neighbor joining phylogenetic trees from env and pol regions and bootscan analyses were employed to subtype the virus from132 HIV-1-infected individuals. HIV-1 subtype B was prevalent in most of the cities under analysis, followed by BF recombinants (9%-35%). HIV-1 subtype C was the most prevalent in Curitiba (46%) and Itajaí (86%) and was also detected in Brasília (9%) and Campo Grande (20%). Pure HIV-1F infections were detected in Rio de Janeiro (9%), Recife (6%), Salvador (6%) and Brasília (9%). Clusters of HIV transmission were assessed by Maximum likelihood analyses and were cross-compared with the RDS network structure. Drug resistance mutations were verified in 12.2% of DUs. Our findings reinforce the importance of the permanent HIV-1 surveillance in distinct Brazilian cities due to viral resistance and increasing subtype heterogeneity all over Brazil, with relevant implications in terms of treatment monitoring, prophylaxis and vaccine development. PMID:26536040

  7. In vivo drug distribution dynamics in thermoablated and normal rabbit livers from biodegradable polymers

    E-print Network

    Gao, Jinming

    : intratumoral drug delivery; Poly(D,L-lactide- co-glycolide); in vivo drug transport; RF ablation; polymer-Targeted Drug Delivery Laboratory, Department of Biomedical Engineering, Case Western Reserve University-guided radiofrequency ablation com- bined with intratumoral drug delivery provides a novel and minimally invasive

  8. Causality assessment of adverse drug reaction in Pulmonology Department of a Tertiary Care Hospital

    PubMed Central

    Khan, Amer; Adil, Mir S.; Nematullah, K.; Ihtisham, S.; Aamer, K.; Aamir, Syed

    2015-01-01

    Background: Adverse drug reaction (ADR) is considered to be the sixth leading cause of death. The incidence rate estimates approximately 2% of hospital admissions are due to ADRs. Objective: To monitor ADRs in Pulmonology department of a tertiary care hospital patient with pulmonary diseases in an inpatient department of pulmonology. Materials and Methods: A prospective, single centered, observational and open labeled study was carried out in Princess Esra Hospital. The patient population was broadly divided into four categories based on diagnosis - chronic obstructive pulmonary disease, Infections, Asthma and Others. Suspected ADRs were reported, analyzed, and causality assessment was carried out using Naranjo's algorithm scale. Results: A total of 302 patients were observed, of which 98 patients experienced ADRs, which accounted for 32.23% of the incidence and totally 160 ADEs were observed. Adult Patients were found to have higher incidence (32.09%) while the incidence rate was slightly greater in geriatric patients (32.39%). The highest incidence of ADEs were found in others group (78.57%). Majority of ADRs were suspected to be due to theophylline (19.39%). Gastrointestinal system (38.75%) was the most common organ system affected due to ADRs. Drug was withdrawn in 12 patients, and specific treatment was administered to 32 patients in view of clinical status. Specific treatment for the management of suspected reaction was administered in 32.65% of ADR reports. Conclusion: A relatively high incidence of adverse drug events (32.2%) have been recorded which shows that not only Geriatric patients, but also adults are more susceptible to adverse drug effects. A number of drugs in combination were used, and ADEs often get multiplied. Careful therapeutic monitoring and dose individualization is necessary. PMID:26229344

  9. Exposure time independent summary statistics for assessment of drug dependent cell line growth inhibition

    PubMed Central

    2014-01-01

    Background In vitro generated dose-response curves of human cancer cell lines are widely used to develop new therapeutics. The curves are summarised by simplified statistics that ignore the conventionally used dose-response curves’ dependency on drug exposure time and growth kinetics. This may lead to suboptimal exploitation of data and biased conclusions on the potential of the drug in question. Therefore we set out to improve the dose-response assessments by eliminating the impact of time dependency. Results First, a mathematical model for drug induced cell growth inhibition was formulated and used to derive novel dose-response curves and improved summary statistics that are independent of time under the proposed model. Next, a statistical analysis workflow for estimating the improved statistics was suggested consisting of 1) nonlinear regression models for estimation of cell counts and doubling times, 2) isotonic regression for modelling the suggested dose-response curves, and 3) resampling based method for assessing variation of the novel summary statistics. We document that conventionally used summary statistics for dose-response experiments depend on time so that fast growing cell lines compared to slowly growing ones are considered overly sensitive. The adequacy of the mathematical model is tested for doxorubicin and found to fit real data to an acceptable degree. Dose-response data from the NCI60 drug screen were used to illustrate the time dependency and demonstrate an adjustment correcting for it. The applicability of the workflow was illustrated by simulation and application on a doxorubicin growth inhibition screen. The simulations show that under the proposed mathematical model the suggested statistical workflow results in unbiased estimates of the time independent summary statistics. Variance estimates of the novel summary statistics are used to conclude that the doxorubicin screen covers a significant diverse range of responses ensuring it is useful for biological interpretations. Conclusion Time independent summary statistics may aid the understanding of drugs’ action mechanism on tumour cells and potentially renew previous drug sensitivity evaluation studies. PMID:24902483

  10. 75 FR 4400 - Draft Guidance for Industry on Assessment of Abuse Potential of Drugs; Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-27

    ...the Controlled Substances Act. Drugs with abuse potential generally include drugs...under medical supervision. If a drug has abuse potential, the Secretary of Health...with the National Institute on Drug Abuse (NIDA), as described in a...

  11. Distributed Energy Resources and Dynamic Microgrid: An Integrated Assessment

    NASA Astrophysics Data System (ADS)

    Shang, Duo Rick

    The overall goal of this thesis is to improve understanding in terms of the benefit of DERs to both utility and to electricity end-users when integrated in power distribution system. To achieve this goal, a series of two studies was conducted to assess the value of DERs when integrated with new power paradigms. First, the arbitrage value of DERs was examined in markets with time-variant electricity pricing rates (e.g., time of use, real time pricing) under a smart grid distribution paradigm. This study uses a stochastic optimization model to estimate the potential profit from electricity price arbitrage over a five-year period. The optimization process involves two types of PHEVs (PHEV-10, and PHEV-40) under three scenarios with different assumptions on technology performance, electricity market and PHEV owner types. The simulation results indicate that expected arbitrage profit is not a viable option to engage PHEVs in dispatching and in providing ancillary services without more favorable policy and PHEV battery technologies. Subsidy or change in electricity tariff or both are needed. Second, it examined the concept of dynamic microgrid as a measure to improve distribution resilience, and estimates the prices of this emerging service. An economic load dispatch (ELD) model is developed to estimate the market-clearing price in a hypothetical community with single bid auction electricity market. The results show that the electricity market clearing price on the dynamic microgrid is predominantly decided by power output and cost of electricity of each type of DGs. At circumstances where CHP is the only source, the electricity market clearing price in the island is even cheaper than the on-grid electricity price at normal times. Integration of PHEVs in the dynamic microgrid will increase electricity market clearing prices. It demonstrates that dynamic microgrid is an economically viable alternative to enhance grid resilience.

  12. Applying Linear and Non-Linear Methods for Parallel Prediction of Volume of Distribution and Fraction of Unbound Drug

    PubMed Central

    del Amo, Eva M.; Ghemtio, Leo; Xhaard, Henri; Yliperttula, Marjo; Urtti, Arto; Kidron, Heidi

    2013-01-01

    Volume of distribution and fraction unbound are two key parameters in pharmacokinetics. The fraction unbound describes the portion of free drug in plasma that may extravasate, while volume of distribution describes the tissue access and binding of a drug. Reliable in silico predictions of these pharmacokinetic parameters would benefit the early stages of drug discovery, as experimental measuring is not feasible for screening purposes. We have applied linear and nonlinear multivariate approaches to predict these parameters: linear partial least square regression and non-linear recursive partitioning classification. The volume of distribution and fraction of unbound drug in plasma are predicted in parallel within the model, since the two are expected to be affected by similar physicochemical drug properties. Predictive models for both parameters were built and the performance of the linear models compared to models included in the commercial software Volsurf+. Our models performed better in predicting the unbound fraction (Q2 0.54 for test set compared to 0.38 with Volsurf+ model), but prediction accuracy of the volume of distribution was comparable to the Volsurf+ model (Q2 of 0.70 for test set compared to 0.71 with Volsurf+ model). The nonlinear classification models were able to identify compounds with a high or low volume of distribution (sensitivity 0.81 and 0.71, respectively, for test set), while classification of fraction unbound was less successful. The interrelationship between the volume of distribution and fraction unbound is investigated and described in terms of physicochemical descriptors. Lipophilicity and solubility descriptors were found to have a high influence on both volume of distribution and fraction unbound, but with an inverse relationship. PMID:24116008

  13. Assessment of the use of oral fluid as a matrix for drug monitoring in patients undergoing treatment for opioid addiction.

    PubMed

    Kunkel, Frank; Fey, Elizabeth; Borg, Damon; Stripp, Richard; Getto, Christine

    2015-01-01

    Drug testing is an important clinical tool that is available to physicians who are assessing the effectiveness of drug treatment as well as patient compliance to the administered program. While urine has traditionally been the matrix of choice for drug monitoring, oral fluid, a filtrate of the blood, has shown great promise as an alternative matrix for such applications. Oral fluid collection can be accomplished without the need for highly trained medical staff through the use of a simple, noninvasive oral fluid collection device, which obtains an adequate sample in only a few minutes. There has been a significant amount of research performed on the use of oral fluid for forensic toxicology application; however, more studies assessing the use of oral fluid drug testing are required to validate its ability to achieve clinical drug monitoring goals. Testing for various drugs in oral fluid may yield a different result when compared to the same drugs in urine, requiring an assessment of the utility of oral fluid for such practices. The purpose of this study was to examine the application of oral fluid drug testing in patients undergoing buprenorphine treatment for opioid dependence. A retrospective analysis of drug testing results obtained from 6,928 patients (4,560 unobserved urine collections and 2,368 observed oral fluid collections) monitored for heroin metabolite, amphetamine, benzodiazepines, buprenorphine, tetrahydrocannabinol, cocaine, codeine, hydrocodone, hydromorphone, methadone, morphine, oxycodone, and oxymorphone was completed. Results of this statistical exercise indicated that patients undergoing observed oral fluid collection tested positive more frequently than those unobserved urine collections for several illicit drugs and prescription medications targeted. Oral fluid was shown to detect illicit drug use as well as noncompliance in this patient population under the studied conditions more often than the urine specimens. PMID:26535971

  14. Drug Use Prevention Data, Missing Assessments and Survival Jennifer M. Bacik1, Susan A. Murphy1, AND James C. Anthony2

    E-print Network

    Murphy, Susan A.

    Drug Use Prevention Data, Missing Assessments and Survival Analysis Jennifer M. Bacik1, Susan A of interest to investigate the incidence of initial drug experimentation or other drug use milestones;1. INTRODUCTION In many drug use prevention studies, researchers are interested in the relationship between

  15. Drug Use Prevention Data, Missing Assessments and Survival Jennifer M. Bacik 1 , Susan A. Murphy 1 , AND James C. Anthony 2

    E-print Network

    Murphy, Susan A.

    Drug Use Prevention Data, Missing Assessments and Survival Analysis Jennifer M. Bacik 1 , Susan A of interest to investigate the incidence of initial drug experimentation or other drug use milestones, Censoring 1 #12; 1. INTRODUCTION In many drug use prevention studies, researchers are interested

  16. Evaluation of higher distribution and/or utilization voltages. Fourth interim report (August 1980): assessment of optimum distribution configuration

    SciTech Connect

    Not Available

    1981-04-01

    This interim report provides documentation on the fourth task, Assessment of Optimum Distribution Configuration, of DOE Contract No. ET-78-C-01-2866, Evaluation of Higher Distribution and/or Utilization Voltages. The work performed under this task includes the development of a computer model for assessment of life cycle costs for the distribution and utilization systems, the development of an optimization algorithm to enable distribution system configuration optimization and a net energy analysis to determine potential net energy savings. Input data for this task derive from Task 3. The major output of this task is a documented computer code.

  17. Literature based drug interaction prediction with clinical assessment using electronic medical records: novel myopathy associated drug interactions.

    PubMed

    Duke, Jon D; Han, Xu; Wang, Zhiping; Subhadarshini, Abhinita; Karnik, Shreyas D; Li, Xiaochun; Hall, Stephen D; Jin, Yan; Callaghan, J Thomas; Overhage, Marcus J; Flockhart, David A; Strother, R Matthew; Quinney, Sara K; Li, Lang

    2012-01-01

    Drug-drug interactions (DDIs) are a common cause of adverse drug events. In this paper, we combined a literature discovery approach with analysis of a large electronic medical record database method to predict and evaluate novel DDIs. We predicted an initial set of 13197 potential DDIs based on substrates and inhibitors of cytochrome P450 (CYP) metabolism enzymes identified from published in vitro pharmacology experiments. Using a clinical repository of over 800,000 patients, we narrowed this theoretical set of DDIs to 3670 drug pairs actually taken by patients. Finally, we sought to identify novel combinations that synergistically increased the risk of myopathy. Five pairs were identified with their p-values less than 1E-06: loratadine and simvastatin (relative risk or RR?=?1.69); loratadine and alprazolam (RR?=?1.86); loratadine and duloxetine (RR?=?1.94); loratadine and ropinirole (RR?=?3.21); and promethazine and tegaserod (RR?=?3.00). When taken together, each drug pair showed a significantly increased risk of myopathy when compared to the expected additive myopathy risk from taking either of the drugs alone. Based on additional literature data on in vitro drug metabolism and inhibition potency, loratadine and simvastatin and tegaserod and promethazine were predicted to have a strong DDI through the CYP3A4 and CYP2D6 enzymes, respectively. This new translational biomedical informatics approach supports not only detection of new clinically significant DDI signals, but also evaluation of their potential molecular mechanisms. PMID:22912565

  18. Literature Based Drug Interaction Prediction with Clinical Assessment Using Electronic Medical Records: Novel Myopathy Associated Drug Interactions

    PubMed Central

    Subhadarshini, Abhinita; Karnik, Shreyas D.; Li, Xiaochun; Hall, Stephen D.; Jin, Yan; Callaghan, J. Thomas; Overhage, Marcus J.; Flockhart, David A.; Strother, R. Matthew; Quinney, Sara K.; Li, Lang

    2012-01-01

    Drug-drug interactions (DDIs) are a common cause of adverse drug events. In this paper, we combined a literature discovery approach with analysis of a large electronic medical record database method to predict and evaluate novel DDIs. We predicted an initial set of 13197 potential DDIs based on substrates and inhibitors of cytochrome P450 (CYP) metabolism enzymes identified from published in vitro pharmacology experiments. Using a clinical repository of over 800,000 patients, we narrowed this theoretical set of DDIs to 3670 drug pairs actually taken by patients. Finally, we sought to identify novel combinations that synergistically increased the risk of myopathy. Five pairs were identified with their p-values less than 1E-06: loratadine and simvastatin (relative risk or RR?=?1.69); loratadine and alprazolam (RR?=?1.86); loratadine and duloxetine (RR?=?1.94); loratadine and ropinirole (RR?=?3.21); and promethazine and tegaserod (RR?=?3.00). When taken together, each drug pair showed a significantly increased risk of myopathy when compared to the expected additive myopathy risk from taking either of the drugs alone. Based on additional literature data on in vitro drug metabolism and inhibition potency, loratadine and simvastatin and tegaserod and promethazine were predicted to have a strong DDI through the CYP3A4 and CYP2D6 enzymes, respectively. This new translational biomedical informatics approach supports not only detection of new clinically significant DDI signals, but also evaluation of their potential molecular mechanisms. PMID:22912565

  19. The use of 2D fingerprint methods to support the assessment of structural similarity in orphan drug legislation

    PubMed Central

    2014-01-01

    Background In the European Union, medicines are authorised for some rare disease only if they are judged to be dissimilar to authorised orphan drugs for that disease. This paper describes the use of 2D fingerprints to show the extent of the relationship between computed levels of structural similarity for pairs of molecules and expert judgments of the similarities of those pairs. The resulting relationship can be used to provide input to the assessment of new active compounds for which orphan drug authorisation is being sought. Results 143 experts provided judgments of the similarity or dissimilarity of 100 pairs of drug-like molecules from the DrugBank 3.0 database. The similarities of these pairs were also computed using BCI, Daylight, ECFC4, ECFP4, MDL and Unity 2D fingerprints. Logistic regression analyses demonstrated a strong relationship between the human and computed similarity assessments, with the resulting regression models having significant predictive power in experiments using data from submissions of orphan drug medicines to the European Medicines Agency. The BCI fingerprints performed best overall on the DrugBank dataset while the BCI, Daylight, ECFP4 and Unity fingerprints performed comparably on the European Medicines Agency dataset. Conclusions Measures of structural similarity based on 2D fingerprints can provide a useful source of information for the assessment of orphan drug status by regulatory authorities. PMID:24485002

  20. Using ICR and SCID mice as animal models for smallpox to assess antiviral drug efficacy.

    PubMed

    Titova, Ksenya A; Sergeev, Alexander A; Zamedyanskaya, Alena S; Galahova, Darya O; Kabanov, Alexey S; Morozova, Anastasia A; Bulychev, Leonid E; Sergeev, Artemiy A; Glotova, Tanyana I; Shishkina, Larisa N; Taranov, Oleg S; Omigov, Vladimir V; Zavjalov, Evgenii L; Agafonov, Alexander P; Sergeev, Alexander N

    2015-09-01

    The possibility of using immunocompetent ICR mice and immunodeficient SCID mice as model animals for smallpox to assess antiviral drug efficacy was investigated. Clinical signs of the disease did not appear following intranasal (i.n.) challenge of mice with strain Ind-3a of variola virus (VARV), even when using the highest possible dose of the virus (5.2 log10 p.f.u.). The 50?% infective doses (ID50) of VARV, estimated by the virus presence or absence in the lungs 3 and 4?days post-infection, were 2.7?±?0.4 log10 p.f.u. for ICR mice and 3.5?±?0.7 log10 p.f.u. for SCID mice. After i.n. challenge of ICR and SCID mice with VARV 30 and 50 ID50, respectively, steady reproduction of the virus occurred only in the respiratory tract (lungs and nose). Pathological inflammatory destructive changes were revealed in the respiratory tract and the primary target cells for VARV (macrophages and epithelial cells) in mice, similar to those in humans and cynomolgus macaques. The use of mice to assess antiviral efficacies of NIOCH-14 and ST-246 demonstrated the compliance of results with those described in scientific literature, which opens up the prospect of their use as an animal model for smallpox to develop anti-smallpox drugs intended for humans. PMID:26067292

  1. Personalized Risk Assessment of Drug-Related Harm Is Associated with Health Outcomes

    PubMed Central

    Jones, Andrea A.; Vila-Rodriguez, Fidel; Panenka, William J.; Leonova, Olga; Strehlau, Verena; Lang, Donna J.; Thornton, Allen E.; Wong, Hubert; Barr, Alasdair M.; Procyshyn, Ric M.; Smith, Geoffrey N.; Buchanan, Tari; Krajden, Mel; Krausz, Michael; Montaner, Julio S.; MacEwan, G. William; Nutt, David J.; Honer, William G.

    2013-01-01

    Background The Independent Scientific Committee on Drugs (ISCD) assigned quantitative scores for harm to 20 drugs. We hypothesized that a personalized, ISCD-based Composite Harm Score (CHS) would be associated with poor health outcomes in polysubstance users. Methods A prospective community sample (n=293) of adults living in marginal housing was assessed for substance use. The CHS was calculated based on the ISCD index, and the personal substance use characteristics over four weeks. Regression models estimated the association between CHS and physical, psychological, and social health outcomes. Results Polysubstance use was pervasive (95.8%), as was multimorbid illness (median 3, possible range 0–12). The median CHS was 2845 (interquartile range 1865–3977). Adjusting for age and sex, every 1000-unit CHS increase was associated with greater mortality (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.07–2.01, p = 0.02), and persistent hepatitis C infection (OR 1.29, 95% CI 1.02–1.67, p = 0.04). The likelihood of substance-induced psychosis increased 1.39-fold (95% CI 1.13–1.67, p = 0.001). The amount spent on drugs increased 1.51-fold (1.40–1.62, p < 0.001) and the odds of having committed a crime increased 1.74-fold (1.46–2.10, p < 0.001). Multimorbid illness increased 1.43-fold (95% CI 1.26–1.63, p < 0.001). Conclusions Greater CHS predicts poorer physical, psychological, and social health, and may be a useful quantitative, personalized measure of risk for drug-related harm. PMID:24223192

  2. 41 CFR 102-41.230 - May SASPs pick up or store donated drug paraphernalia in their distribution centers?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 41 Public Contracts and Property Management 3 2013-07-01 2013-07-01 false May SASPs pick up or store donated drug paraphernalia in their distribution centers? 102-41.230 Section 102-41.230 Public Contracts and Property Management Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION PERSONAL PROPERTY...

  3. 41 CFR 105-74.210 - To whom must I distribute my drug-free workplace statement?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 41 Public Contracts and Property Management 3 2013-07-01 2013-07-01 false To whom must I distribute my drug-free workplace statement? 105-74.210 Section 105-74.210 Public Contracts and Property Management Federal Property Management Regulations System (Continued) GENERAL SERVICES ADMINISTRATION Regional Offices-General Services Administration...

  4. On the assessment of adverse drug reactions from spontaneous reporting systems: the influence of under-reporting on odds ratios.

    PubMed

    van der Heijden, Peter G M; van Puijenbroek, Eugène P; van Buuren, Stef; van der Hofstede, Jacques W

    2002-07-30

    A well-known problem in spontaneous reporting systems (SRSs) for adverse drug reactions (ADRs) is under-reporting, that is, the problem that not all occurrences of ADRs are reported to the SRS. We look at the question of how to draw statistical conclusions from analyses of SRS data using reporting odds ratios. We will show that certain under-reporting problems play no role in assessing ADRs from SRSs: the results from the analyses turn out to be biased by some specific under-reporting problems, but not by others. SRS data can be particularly useful for the assessment of drug-drug interactions. If the assumption holds that there is an under-reporting problem for a first drug, and an under-reporting problem for a second drug, but that these two under-reporting problems do not influence each other, then reporting odds ratios estimated from SRSs are useful for signalling drug-drug interactions in the ADR-experiencing population. Similar results hold for covariate-drug interactions. We illustrate our results using two examples. PMID:12111885

  5. 10 CFR 32.72 - Manufacture, preparation, or transfer for commercial distribution of radioactive drugs containing...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... requirements specified in 10 CFR 30.33; (2) The applicant submits evidence that the applicant is at least one... processing of a drug under 21 CFR 207.20(a); (ii) Registered or licensed with a state agency as a drug... prepare radioactive drugs for medical use, as defined in 10 CFR 35.2, provided that the radioactive...

  6. 10 CFR 32.72 - Manufacture, preparation, or transfer for commercial distribution of radioactive drugs containing...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... requirements specified in 10 CFR 30.33; (2) The applicant submits evidence that the applicant is at least one... processing of a drug under 21 CFR 207.20(a); (ii) Registered or licensed with a state agency as a drug... prepare radioactive drugs for medical use, as defined in 10 CFR 35.2, provided that the radioactive...

  7. 10 CFR 32.72 - Manufacture, preparation, or transfer for commercial distribution of radioactive drugs containing...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... requirements specified in 10 CFR 30.33; (2) The applicant submits evidence that the applicant is at least one... processing of a drug under 21 CFR 207.20(a); (ii) Registered or licensed with a state agency as a drug... prepare radioactive drugs for medical use, as defined in 10 CFR 35.2, provided that the radioactive...

  8. 10 CFR 32.72 - Manufacture, preparation, or transfer for commercial distribution of radioactive drugs containing...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... requirements specified in 10 CFR 30.33; (2) The applicant submits evidence that the applicant is at least one... processing of a drug under 21 CFR 207.20(a); (ii) Registered or licensed with a state agency as a drug... prepare radioactive drugs for medical use, as defined in 10 CFR 35.2, provided that the radioactive...

  9. 10 CFR 32.72 - Manufacture, preparation, or transfer for commercial distribution of radioactive drugs containing...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... requirements specified in 10 CFR 30.33; (2) The applicant submits evidence that the applicant is at least one... processing of a drug under 21 CFR 207.20(a); (ii) Registered or licensed with a state agency as a drug... prepare radioactive drugs for medical use, as defined in 10 CFR 35.2, provided that the radioactive...

  10. The Distributive Impact Assessment Model (DIAM): Technology share component

    SciTech Connect

    Poyer, D.A.; Earl, E.; Bonner, B.

    1995-03-01

    The models described in this report are used to allocate total energy consumption in an energy end-use service area by fuel type (including electricity) within the Distributive Impact Assessment Model (DIAM) framework. The primary objective of the DIAM is to provide energy consumption and expenditure forecasts for different population categories that are consistent with the US Department of Energy (DOE) Energy Information Administration`s (EIA`s) National Energy Modeling System (NEMS) forecast, which is produced annually in the Annual Energy Outlook and periodically in support of DOE policy formulation and analysis. The models are multinominal logit models that have been estimated using EIA`s 1990 Residential Energy Consumption Survey. Three models were estimated: space heating share, water heating share, and cooking share. These models are used to allocate total end-use service consumption over different technologies defined by fuel type characteristics. For each of the end-use service categories, consumption shares are estimated for a subset of six fuel types: natural gas, electricity, liquid petroleum gas, fuel oil/kerosene, wood, and other fuel.

  11. Phospholipid vesicle-based permeation assay and EpiSkin® in assessment of drug therapies destined for skin administration.

    PubMed

    Engesland, André; Škalko-Basnet, Nataša; Flaten, Gøril Eide

    2015-03-01

    Cost-effective and efficient methods for permeability screening are crucial during early development of drugs, drug formulations, and cosmeceuticals. Alternatives to animal experiments are impelled for both economical and ethical reasons. The aim of this study was to determine the ability of the phospholipid vesicle-based permeation assay (PVPA) to assess the effect of different formulations on drug permeability and thus establish its utility in formulation development. Three model drugs were tested in solutions and as liposomal formulations. The permeability results for the PVPA models were compared with the results for the reconstructed human skin model, EpiSkin(®). The drugs were ranked based on their estimated penetration potentials, and the results were in accordance with what was expected considering the physicochemical properties of the drugs. PVPAs (E-80, ceramide, cholesterol, cholesteryl sulfate, and palmitic acid) was able to distinguish between drug solutions and liposomal formulations; however, EpiSkin(®) detected only small differences between the drugs in solution and formulations. In contrast with EpiSkin(®), which is limited by a 3-day testing window, PVPA barriers can be stored frozen for up to 2 weeks or even up to 16 months, depending on their compositions. The PVPA models are thus more cost effective and efficient than the EpiSkin(®) model for permeability screening during early drug development. PMID:25558045

  12. Evolution of health technology assessment: best practices of the pan-Canadian Oncology Drug Review

    PubMed Central

    Rocchi, Angela; Chabot, Isabelle; Glennie, Judith

    2015-01-01

    Background In 2007, Canada chose to develop a separate and distinct path for oncology drug health technology assessment (HTA). In 2013, the decision was made to transfer the pan-Canadian Oncology Drug Review (pCODR) to the Canadian Agency for Drugs and Technologies in Health (CADTH), to align the pCODR and CADTH Common Drug Review processes while building on the best practices of both. The objective of this research was to conduct an examination of the best practices established by the pCODR. Methods A qualitative research approach was taken to assess the policies, processes, and practices of the pCODR, based on internationally accepted best practice “principles” in HTA, with a particular focus on stakeholder engagement. Publicly available information regarding the approach of the pCODR was used to gauge the agency’s performance against these principles. In addition, stakeholder observations and real-world experiences were gathered through key informant interviews to be inclusive of perspectives from patient advocacy groups, provincial and/or cancer agency decision-makers, community and academic oncologists, industry, expert committee members, and health economists. Results This analysis indicated that, through the pCODR, oncology stakeholders have had a voice in and have come to trust the quality and relevance of oncology HTA as a vital tool to ensure the best decisions for Canadians with cancer and their health care system. It could be expected that adoption of the principles and processes of the pCODR would bring a similar level of engagement and trust to other HTA organizations in Canada and elsewhere. Conclusion The results of this research led to recommendations for improvement and potential extrapolation of these best practices to other HTA organizations worldwide, along with suggestions for continued evolution of the pCODR in conjunction with its integration into the CADTH. It is clear that the transition of the pCODR to CADTH provides an opportunity for practices initiated by the pCODR to become the standard for these newly amalgamated HTA agencies in Canada. PMID:26082654

  13. Rapid assessment of HIV risk behavior in drug using sex workers in three cities in South Africa.

    PubMed

    Parry, Charles D H; Dewing, Sarah; Petersen, Petal; Carney, Tara; Needle, Richard; Kroeger, Karen; Treger, Latasha

    2009-10-01

    A rapid assessment was undertaken with drug using commercial sex workers (CSWs) to investigate practices putting them at risk for contracting HIV. It included key informant (KI) (N = 67) and focus group (N = 10) interviews in locations with a high prevalence of drug use in Cape Town, Durban and Pretoria, South Africa. HIV testing of KIs was conducted. Cocaine, Ecstasy, heroin and methaqualone are used by CSWs prior to, during and after sex. Drugs enhance the sexual experience and prolong sex sessions. Interviews revealed inconsistent condom use among CSWs together with other risky sexual practices such as needle sharing. Among CSWs who agreed to HIV testing, 34% tested positive. Barriers to accessing drug treatment and HIV treatment and preventive services were identified. Interventions recognizing the role of drug abuse in HIV transmission should be prioritized, and issues of access to services, stigma and power relations must be considered. PMID:18324470

  14. Assessment of a candidate marker constituent predictive of a dietary substance-drug interaction: case study with grapefruit juice and CYP3A4 drug substrates.

    PubMed

    Ainslie, Garrett R; Wolf, Kristina K; Li, Yingxin; Connolly, Elizabeth A; Scarlett, Yolanda V; Hull, J Heyward; Paine, Mary F

    2014-12-01

    Dietary substances, including herbal products and citrus juices, can perpetrate interactions with conventional medications. Regulatory guidances for dietary substance-drug interaction assessment are lacking. This deficiency is due in part to challenges unique to dietary substances, a lack of requisite human-derived data, and limited jurisdiction. An in vitro-in vivo extrapolation (IVIVE) approach to help address some of these hurdles was evaluated using the exemplar dietary substance grapefruit juice (GFJ), the candidate marker constituent 6',7'-dihydroxybergamottin (DHB), and the purported victim drug loperamide. First, the GFJ-loperamide interaction was assessed in 16 healthy volunteers. Loperamide (16 mg) was administered with 240 ml of water or GFJ; plasma was collected from 0 to 72 hours. Relative to water, GFJ increased the geometric mean loperamide area under the plasma concentration-time curve (AUC) significantly (1.7-fold). Second, the mechanism-based inhibition kinetics for DHB were recovered using human intestinal microsomes and the index CYP3A4 reaction, loperamide N-desmethylation (KI [concentration needed to achieve one-half kinact], 5.0 ± 0.9 µM; kinact [maximum inactivation rate constant], 0.38 ± 0.02 minute(-1)). These parameters were incorporated into a mechanistic static model, which predicted a 1.6-fold increase in loperamide AUC. Third, the successful IVIVE prompted further application to 15 previously reported GFJ-drug interaction studies selected according to predefined criteria. Twelve of the interactions were predicted to within the 25% predefined criterion. Results suggest that DHB could be used to predict the CYP3A4-mediated effect of GFJ. This time- and cost-effective IVIVE approach could be applied to other dietary substance-drug interactions to help prioritize new and existing drugs for more advanced (dynamic) modeling and simulation and clinical assessment. PMID:25253884

  15. Assessment of a Candidate Marker Constituent Predictive of a Dietary Substance–Drug Interaction: Case Study with Grapefruit Juice and CYP3A4 Drug Substrates

    PubMed Central

    Ainslie, Garrett R.; Wolf, Kristina K.; Li, Yingxin; Connolly, Elizabeth A.; Scarlett, Yolanda V.; Hull, J. Heyward

    2014-01-01

    Dietary substances, including herbal products and citrus juices, can perpetrate interactions with conventional medications. Regulatory guidances for dietary substance–drug interaction assessment are lacking. This deficiency is due in part to challenges unique to dietary substances, a lack of requisite human-derived data, and limited jurisdiction. An in vitro–in vivo extrapolation (IVIVE) approach to help address some of these hurdles was evaluated using the exemplar dietary substance grapefruit juice (GFJ), the candidate marker constituent 6?,7?-dihydroxybergamottin (DHB), and the purported victim drug loperamide. First, the GFJ-loperamide interaction was assessed in 16 healthy volunteers. Loperamide (16 mg) was administered with 240 ml of water or GFJ; plasma was collected from 0 to 72 hours. Relative to water, GFJ increased the geometric mean loperamide area under the plasma concentration–time curve (AUC) significantly (1.7-fold). Second, the mechanism-based inhibition kinetics for DHB were recovered using human intestinal microsomes and the index CYP3A4 reaction, loperamide N-desmethylation (KI [concentration needed to achieve one-half kinact], 5.0 ± 0.9 µM; kinact [maximum inactivation rate constant], 0.38 ± 0.02 minute?1). These parameters were incorporated into a mechanistic static model, which predicted a 1.6-fold increase in loperamide AUC. Third, the successful IVIVE prompted further application to 15 previously reported GFJ-drug interaction studies selected according to predefined criteria. Twelve of the interactions were predicted to within the 25% predefined criterion. Results suggest that DHB could be used to predict the CYP3A4-mediated effect of GFJ. This time- and cost-effective IVIVE approach could be applied to other dietary substance–drug interactions to help prioritize new and existing drugs for more advanced (dynamic) modeling and simulation and clinical assessment. PMID:25253884

  16. Mining hidden knowledge for drug safety assessment: topic modeling of LiverTox as a case study

    PubMed Central

    2014-01-01

    Background Given the significant impact on public health and drug development, drug safety has been a focal point and research emphasis across multiple disciplines in addition to scientific investigation, including consumer advocates, drug developers and regulators. Such a concern and effort has led numerous databases with drug safety information available in the public domain and the majority of them contain substantial textual data. Text mining offers an opportunity to leverage the hidden knowledge within these textual data for the enhanced understanding of drug safety and thus improving public health. Methods In this proof-of-concept study, topic modeling, an unsupervised text mining approach, was performed on the LiverTox database developed by National Institutes of Health (NIH). The LiverTox structured one document per drug that contains multiple sections summarizing clinical information on drug-induced liver injury (DILI). We hypothesized that these documents might contain specific textual patterns that could be used to address key DILI issues. We placed the study on drug-induced acute liver failure (ALF) which was a severe form of DILI with limited treatment options. Results After topic modeling of the "Hepatotoxicity" sections of the LiverTox across 478 drug documents, we identified a hidden topic relevant to Hy's law that was a widely-accepted rule incriminating drugs with high risk of causing ALF in humans. Using this topic, a total of 127 drugs were further implicated, 77 of which had clear ALF relevant terms in the "Outcome and management" sections of the LiverTox. For the rest of 50 drugs, evidence supporting risk of ALF was found for 42 drugs from other public databases. Conclusion In this case study, the knowledge buried in the textual data was extracted for identification of drugs with potential of causing ALF by applying topic modeling to the LiverTox database. The knowledge further guided identification of drugs with the similar potential and most of them could be verified and confirmed. This study highlights the utility of topic modeling to leverage information within textual drug safety databases, which provides new opportunities in the big data era to assess drug safety. PMID:25559675

  17. Duplex quantitative Reverse-Transcriptase PCR for simultaneous assessment of drug activity against Leishmania intracellular amastigotes and their host cells.

    PubMed

    van den Bogaart, Erika; Schoone, Gerard J; Adams, Emily R; Schallig, Henk D F H

    2014-04-01

    Currently available drugs for treatment of Leishmania infections are highly toxic and drug resistance to first line therapies has been observed. New, safer and more effective drugs are urgently needed to improve clinical resolution of the disease and reduce the risks associated with it. High-throughput screening of new compounds against cultured promastigotes is easy to perform, but the results are poorly predictive of in vivo efficacy. Intra-macrophage amastigote models provide a better proxy of the clinically relevant stage of disease and should be routinely implemented in the search for new anti-leishmanial agents, despite being labor intensive. This study describes the use of a duplex quantitative Reverse-Transcriptase PCR (qRT-PCR) for assessment of drug activity against Leishmania intracellular amastigotes and their host cells. The assay simultaneously quantifies Leishmania 18S ribosomal RNA and the human ?2-microglobulin (?-2M) mRNA, used for monitoring drug cytotoxicity and test performance. Accurate determination of parasite viability by the newly developed qRT-PCR was confirmed by parallel assessment of compound performance against standard microscopy. Highly reproducible anti-leishmanial activities were obtained with a set of structurally- and pharmacologically-diverse compounds, whose toxicity against host cells correlated with a low ?-2M amplification. Sensitive and versatile, this duplex qRT-PCR offers a valuable tool for assessment of drug activities against Leishmania amastigotes and their host cells. PMID:24596664

  18. An assessment of the use of drug and non-drug interventions in the treatment of Ichthyophthirius multifiliis Fouquet, 1876, a protozoan parasite of freshwater fish.

    PubMed

    Picón-Camacho, S M; Marcos-Lopez, M; Bron, J E; Shinn, A P

    2012-02-01

    Infection by the ciliate protozoan Ichthyophthirius multifiliis Fouquet, 1876 causes significant economic losses in freshwater aquaculture worldwide. Following the ban on the use of malachite green for treating food fish, there has been extensive research aimed at identifying suitable replacements. In this paper we critically assess drug and non-drug interventions, which have been tested for use or have been employed against this parasite and evaluate possibilities for their application in farm systems. Current treatments include the administration of formaldehyde, sodium chloride (salt), copper sulphate and potassium permanganate. However, purportedly more environmentally friendly drugs such as humic acid, potassium ferrate (VI), bronopol and the peracetic acid-based products have recently been tested and represent promising alternatives. Further investigation, is required to optimize the treatments and to establish precise protocols in order to minimize the quantity of drug employed whilst ensuring the most efficacious performance. At the same time, there needs to be a greater emphasis placed on the non-drug aspects of management strategies, including the use of non-chemical interventions focusing on the removal of free-swimming stages and tomocysts of I. multifiliis from farm culture systems. Use of such strategies provides the hope of more environmentally friendly alternatives for the control of I. multifiliis infections. PMID:22078025

  19. Drug release-modulating mechanism of hydrophilic hydroxypropylmethylcellulose matrix tablets: distribution of atoms and carrier and texture analysis.

    PubMed

    Park, Jun-Bom; Lim, Jisung; Kang, Chin-Yang; Lee, Beom-Jin

    2013-12-01

    Although release profiles of drug from hydrophilic matrices have been well recognized, the visual distribution of hydroxypropylmethylcellulose (HPMC) and atoms inside of internal structures of hydrophilic HPMC matrices has not been characterized. In this paper, drug release mechanism from HPMC matrix tablet was investigated based on the release behaviors of HPMC, physical properties of gelled HPMC tablet and atomic distributions of formulation components using diverse instruments. A matrix tablet consisting of hydroxypropyl methylcellulose (HPMC 6, 4,000 and 100,000 mPa·s), chlorpheniramine maleate (CPM) as a model and fumed silicon dioxide (Aerosil(®) 200) was prepared via direct compression. The distribution of atoms and HPMC imaging were characterized using scanning electron microscope (SEM)/ energy-dispersive X-ray spectroscopy (EDX), and near-infrared (NIR) analysis, respectively as a function of time. A texture analyzer was also used to characterize the thickness and maintenance of gel layer of HPMC matrix tablet. The HPMC matrix tablets showed Higuchi release kinetics with no lag time against the square root of time. High viscosity grades of HPMC gave retarded release rate because of the greater swelling and gel thickness as characterized by texture analyzer. According to the NIR imaging, low-viscosity-grade HPMC (6 mPa·s) quickly leached out onto the surface of the tablet, while the high-viscosity-grade HPMC (4000 mPa·s) formed much thicker gel layer around the tablet and maintained longer via slow erosion, resulting in retarded drug release. The atomic distribution of the drug (chlorine, carbon, oxygen), HPMC (carbon, oxygen) and silicon dioxide (silica, oxygen) and NIR imaging of HPMC corresponded with the dissolution behaviors of drug as a function of time. The use of imaging and texture analyses could be applicable to explain the release- modulating mechanism of hydrophilic HPMC matrix tablets. PMID:23855499

  20. Learn More about Normal Distribution | Dietary Assessment Primer

    Cancer.gov

    In statistics, the "distribution function" of a random variable is a function that specifies the probability that the variable's observed value will lie in any given region of possible values. The "normal distribution" is the most commonly used distribution in statistics. A variable that is normally distributed has a histogram (or "density function") that is bell-shaped, with only one peak, and is symmetric around the mean.

  1. Subcellular daunorubicin distribution and its relation to multidrug resistance phenotype in drug-resistant cell line SMMC-7721/R

    PubMed Central

    Yang, Jia-Yin; Luo, Hua-You; Lin, Qi-Yuan; Liu, Zi-Ming; Yan, Lu-Nan; Lin, Ping; Zhang, Jie; Lei, Shong

    2002-01-01

    AIM: To investigate the correlation between subcellular daunorubicin distribution and the multidrug resistance phenotype in drug-resistant cell line SMMC-7721/R. METHODS: The multidrug resistant cell line SMMC-7721/R, a human hepatocellular carcinoma cell line, was established. Antisense oligonucleotides (AS-ODN) were used to obtain different multidrug resistance phenotypes by inhibiting the expression of mdr1 gene and/or multidrug resistance-related protein gene (mrp) using Lipofectamine as delivery agent. Expression of mdr1 and mrp genes was evaluated by RT-PCR and Western blotting. Intracellular daunorubicin (DNR) concentration was measured by flow cytometry. Subcellular DNR distribution was analyzed by confocal laser scanning microscopy. Adriamycin (ADM) and DNR sensitivity was examined by MTT method. RESULTS: Low level expression of mdr1 and mrp mRNAs and no expression of P-Glycoprotein (P-gp) and multidrug resistance-related protein (P190) were detected in parental sensitive cells SMMC-7721/S, but over-expression of these two genes was observed in drug-resistant cell SMMC-7721/R. The expression of mdr1 and mrp genes in SMMC-7721/R cells was down-regulated to the level in the SMMC-7721/S cells by AS-ODN. Intracellular DNR concentration in SMMC-7721/S cells was 10 times higher than that in SMMC-7721/R cells. In SMMC7721/S cells intracellular DNR distributed evenly in the nucleus and cytoplasm, while in SMMC-7721/R cells DNR distributed in a punctate pattern in the cytoplasm and was reduced in the nucleus. DNR concentration in SMMC-7721/R cells co-transfected with AS-ODNs targeting to mdr1 and mrp mRNAs recovered to 25 percent of that in SMMC7721/S cells. Intracellular DNR distribution pattern in drug-resistant cells treated by AS-ODN was similar to drug-sensitive cell, and the cells resistance index (RI) to DNR and ADM decreased at most from 88.0 and 116.0 to 4.0 and 2.3, respectively. Co-Transfection of two AS-ODNs showed a stronger synergistic effect than separate transfection. CONCLUSIONS: P-gp and P190 are two members mediating MDR in cell line SMMC7721/R. Intracellular drug concentration increase and subcellular distribution change are two important factors in multidrug resistance (MDR) formation. The second factor, drugs transport by P-gp and P190 from cell nucleus to organell in cytoplasm, may play a more important role. PMID:12174371

  2. Independent Orbiter Assessment (IOA): Assessment of the Electrical Power Distribution and Control Subsystem, Volume 2

    NASA Technical Reports Server (NTRS)

    Schmeckpeper, K. R.

    1988-01-01

    The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA first completed an analysis of the Electrical Power Distribution and Control (EPD and C) hardware, generating draft failure modes and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The IOA results were then compared to the NASA FMEA/CIL baseline with proposed Post 51-L updates included. A resolution of each discrepancy from the comparison is provided through additional analysis as required. This report documents the results of that comparison for the Orbiter EPD and C hardware. Volume 2 continues the presentation of IOA worksheets.

  3. Independent Orbiter Assessment (IOA): Assessment of the electrical power distribution and control subsystem, volume 3

    NASA Technical Reports Server (NTRS)

    Schmeckpeper, K. R.

    1988-01-01

    The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA first completed an analysis of the Electrical Power Distribution and Control (EPD and C) hardware, generating draft failure modes and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The IOA results were then compared to the NASA FMEA/CIL baseline with proposed Post 51-L updates included. A resolution of each discrepancy from the comparison is provided through additional analysis as required. This report documents the results of that comparison for the Orbiter EPD and C hardware. Volume 3 continues the presentation of IOA worksheets and contains the potential critical items list and the NASA FMEA to IOA worksheet cross reference and recommendations.

  4. Anti-addiction drug ibogaine inhibits voltage-gated ionic currents: A study to assess the drug's cardiac ion channel profile

    SciTech Connect

    Koenig, Xaver; Kovar, Michael; Rubi, Lena; Mike, Agnes K.; Lukacs, Peter; Gawali, Vaibhavkumar S.; Todt, Hannes; Hilber, Karlheinz; Sandtner, Walter

    2013-12-01

    The plant alkaloid ibogaine has promising anti-addictive properties. Albeit not licenced as a therapeutic drug, and despite hints that ibogaine may perturb the heart rhythm, this alkaloid is used to treat drug addicts. We have recently reported that ibogaine inhibits human ERG (hERG) potassium channels at concentrations similar to the drugs affinity for several of its known brain targets. Thereby the drug may disturb the heart's electrophysiology. Here, to assess the drug's cardiac ion channel profile in more detail, we studied the effects of ibogaine and its congener 18-Methoxycoronaridine (18-MC) on various cardiac voltage-gated ion channels. We confirmed that heterologously expressed hERG currents are reduced by ibogaine in low micromolar concentrations. Moreover, at higher concentrations, the drug also reduced human Na{sub v}1.5 sodium and Ca{sub v}1.2 calcium currents. Ion currents were as well reduced by 18-MC, yet with diminished potency. Unexpectedly, although blocking hERG channels, ibogaine did not prolong the action potential (AP) in guinea pig cardiomyocytes at low micromolar concentrations. Higher concentrations (? 10 ?M) even shortened the AP. These findings can be explained by the drug's calcium channel inhibition, which counteracts the AP-prolonging effect generated by hERG blockade. Implementation of ibogaine's inhibitory effects on human ion channels in a computer model of a ventricular cardiomyocyte, on the other hand, suggested that ibogaine does prolong the AP in the human heart. We conclude that therapeutic concentrations of ibogaine have the propensity to prolong the QT interval of the electrocardiogram in humans. In some cases this may lead to cardiac arrhythmias. - Highlights: • We study effects of anti-addiction drug ibogaine on ionic currents in cardiomyocytes. • We assess the cardiac ion channel profile of ibogaine. • Ibogaine inhibits hERG potassium, sodium and calcium channels. • Ibogaine’s effects on ion channels are a potential source of cardiac arrhythmias. • 18-Methoxycoronaridine has a lower affinity for cardiac ion channels than ibogaine.

  5. 75 FR 4400 - Draft Guidance for Industry on Assessment of Abuse Potential of Drugs; Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-27

    ... Abuse (NIDA), as described in a Memorandum of Understanding (MOU) of March 8, 1985 (50 FR 9518). When a... Controlled Substances Act. Drugs with abuse potential generally include drugs that affect the central nervous system, drugs that are chemically or pharmacologically similar to other drugs with known abuse...

  6. Blood-brain barrier in vitro models as tools in drug discovery: assessment of the transport ranking of antihistaminic drugs.

    PubMed

    Neuhaus, W; Mandikova, J; Pawlowitsch, R; Linz, B; Bennani-Baiti, B; Lauer, R; Lachmann, B; Noe, C R

    2012-05-01

    In the course of our validation program testing blood-brain barrier (BBB) in vitro models for their usability as tools in drug discovery it was evaluated whether an established Transwell model based on porcine cell line PBMEC/C1-2 was able to differentiate between the transport properties of first and second generation antihistaminic drugs. First generation antihistamines can permeate the BBB and act in the central nervous system (CNS), whereas entry to the CNS of second generation antihistamines is restricted by efflux pumps such as P-glycoprotein (P-gP) located in brain endothelial cells. P-gP functionality of PBMEC/C1-2 cells grown on Transwell filter inserts was proven by transport studies with P-gP substrate rhodamine 123 and P-gP blocker verapamil. Subsequent drug transport studies with the first generation antihistamines promethazine, diphenhydramine and pheniramine and the second generation antihistamines astemizole, ceterizine, fexofenadine and loratadine were accomplished in single substance as well as in group studies. Results were normalised to diazepam, an internal standard for the transcellular transport route. Moreover, effects after addition of P-gP inhibitor verapamil were investigated. First generation antihistamine pheniramine permeated as fastest followed by diphenhydramine, diazepam, promethazine and second generation antihistaminic drugs ceterizine, fexofenadine, astemizole and loratadine reflecting the BBB in vivo permeability ranking well. Verapamil increased the transport rates of all second generation antihistamines, which suggested involvement of P-gP during their permeation across the BBB model. The ranking after addition of verapamil was significantly changed, only fexofenadine and ceterizine penetrated slower than internal standard diazepam in the presence of verapamil. In summary, permeability data showed that the BBB model based on porcine cell line PBMEC/C1-2 was able to reflect the BBB in vivo situation for the transport of antihistaminc drugs and to distinguish between first and second generation antihistamines. PMID:22764578

  7. Causes and consequences of increasing club drug use in China: a descriptive assessment.

    PubMed

    Yang, Xiushi; Xia, Guomei

    2010-01-01

    Club drugs have quickly become the most widespread "drugs of abuse" in China. Using data from a convenience sample of 730 club drug users in Shanghai in 2006 , we explored the causes and consequences of club drug use. Descriptive analyses suggest that club drug use is typically polydrug use. Polydrug use is strongly associated with weakened social control, drug use social influences, and a sensation-seeking personality; in addition, it is associated with more negative health and social consequences. Both polydrug and single-club-drug users are at high risk of sexually acquiring and/or transmitting HIV. The study's limitations are noted, and future research is suggested. PMID:20025450

  8. Detecting drug-induced prolongation of the QRS complex: New insights for cardiac safety assessment

    SciTech Connect

    Cros, C.; Skinner, M.; Moors, J.; Lainee, P.; Valentin, J.P.

    2012-12-01

    Background: Drugs slowing the conduction of the cardiac action potential and prolonging QRS complex duration by blocking the sodium current (I{sub Na}) may carry pro-arrhythmic risks. Due to the frequency-dependent block of I{sub Na}, this study assesses whether activity-related spontaneous increases in heart rate (HR) occurring during standard dog telemetry studies can be used to optimise the detection of class I antiarrhythmic-induced QRS prolongation. Methods: Telemetered dogs were orally dosed with quinidine (class Ia), mexiletine (class Ib) or flecainide (class Ic). QRS duration was determined standardly (5 beats averaged at rest) but also prior to and at the plateau of each acute increase in HR (3 beats averaged at steady state), and averaged over 1 h period from 1 h pre-dose to 5 h post-dose. Results: Compared to time-matched vehicle, at rest, only quinidine and flecainide induced increases in QRS duration (E{sub max} 13% and 20% respectively, P < 0.01–0.001) whereas mexiletine had no effect. Importantly, the increase in QRS duration was enhanced at peak HR with an additional effect of + 0.7 ± 0.5 ms (quinidine, NS), + 1.8 ± 0.8 ms (mexiletine, P < 0.05) and + 2.8 ± 0.8 ms (flecainide, P < 0.01) (calculated as QRS at basal HR-QRS at high HR). Conclusion: Electrocardiogram recordings during elevated HR, not considered during routine analysis optimised for detecting QT prolongation, can be used to sensitise the detection of QRS prolongation. This could prove useful when borderline QRS effects are detected. Analysing during acute increases in HR could also be useful for detecting drug-induced effects on other aspects of cardiac function. -- Highlights: ? We aimed to improve detection of drug-induced QRS prolongation in safety screening. ? We used telemetered dogs to test class I antiarrhythmics at low and high heart rate. ? At low heart rate only quinidine and flecainide induced an increase in QRS duration. ? At high heart rate the effects of two out of three antiarrhythmics were enhanced. ? Detection of a drug-induced prolongation of QRS was improved at high heart rate.

  9. Comparison of equilibrium and non-equilibrium distribution coefficients for the human drug carbamazepine in soil.

    PubMed

    Williams, C F; Watson, J E; Nelson, S D

    2014-01-01

    The distribution coefficient (KD) for the human drug carbamazepine was measured using a non-equilibrium technique. Repacked soil columns were prepared using an Airport silt loam (Typic Natrustalf) with an average organic matter content of 2.45%. Carbamazepine solutions were then leached through the columns at 0.5, 1.0 and 1.5 mL min(-1) representing average linear velocities of 1.8, 3.5 and 5.3 cm h(-1) respectively. Each flow rate was replicated three times and three carbamazepine pulses were applied to each column resulting in a total of 9 columns with 27 total carbamazepine pulses. Breakthrough curves were used to determine KD using the parameter fitting software CXTFIT. Results indicate that as flow rate decreased from 5.3 to 1.8 cm h(-1), KD increased an average of 21%. Additionally, KD determined by column leaching (14.7-22.7 L kg(-1)) was greater than KD determined by a 2h batch equilibrium adsorption (12.6 L kg(-1)). Based on these KD's carbamazepine would be generally characterized as non-mobile in the soil investigated. However, repeated carbamazepine applications resulted in an average 22% decrease in KD between the first and third applications. Decreasing KD is attributed to differences in sorption site kinetics and carbamazepine residence time in contact with the soil. This would indicate that the repeated use of reclaimed wastewater at high application rates for long-term irrigation or groundwater recharge has the potential to lead to greater transport of carbamazepine than KD determined by batch equilibrium would predict. PMID:24050717

  10. Development of a Questionnaire to Assess Drug Abuse among High School Students of Isfahan Province, Iran: An Action Research

    PubMed Central

    Geramian, Nahid; Gharaat, Leila; Taheri, Shohreh Akhavan; Mohebpour, Fatemeh; Nahvizadeh, Mahmonir; Farajzadegan, Ziba; Heidari, Kamal

    2014-01-01

    Background: Considering the problem of drug abuse in Iran especially in adolescents and the youth, recent alterations in drug abuse rate and its trend, the necessity to have local information about this problem, applied research has a determining role in management of this problem and making proper decisions. Therefore, the current study was conducted to develop a questionnaire to assess the status of drug abuse among high school students of Isfahan Province, Iran. Methods: This cross-sectional study was conducted out in 2009 in 20 cities of Isfahan Province. A researcher-made questionnaire was developed to determine knowledge, attitude, and practice of high school students regarding addictive drugs and their associated causes. This was accomplished by recruiting 7137 students who were selected by multistage random cluster sampling. Results: The designed questionnaire identified the status quo of drug abuse according to age, gender, and different cities of Isfahan Province. We also accessed information about the type of abused drug, the most common causes of drug abuse for the first time, the most important causes of drug abuse, mean age of abusers and mean age at the first abuse, common time and locations of drug abuse, and the most common routes of drug abuse according to gender as well as urban and rural areas of Isfahan Province. Reliability of the questionnaire, based on the calculated Cronbach's alpha coefficient, was 77% considering a cut-off point of 0.07. Conclusions: According to the obtained results, the designed questionnaire is capable to assess the drug abuse status among high school students of Isfahan Province. Regarding the importance of teenage years in forming the future behaviors of adolescents and the opportunities provided at schools, it is prudent to pay more attention to interventions in this age group in order to increase their knowledge and correct their attitude toward illegal drugs and strengthening their confidence in this regard. These interventions can have an important role in decreasing the rate of drug abuse in this age group and consequently in the whole community. PMID:26157565

  11. 77 FR 59156 - Antimicrobial Animal Drug Sales and Distribution Reporting; Extension of Comment Period

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-26

    ... rulemaking that published July 27, 2012 (77 FR 44177) is extended. Submit written or electronic comments by.... Background In the Federal Register of July 27, 2012 (77 FR 44177), FDA published an advance notice of... SERVICES Food and Drug Administration 21 CFR Part 514 Antimicrobial Animal Drug Sales and...

  12. 7 CFR 1230.74 - Prohibited use of distributed assessments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PORK PROMOTION, RESEARCH, AND CONSUMER INFORMATION Pork Promotion, Research, and Consumer Information Order Expenses and Assessments §...

  13. 7 CFR 1230.73 - Uses of distributed assessments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PORK PROMOTION, RESEARCH, AND CONSUMER INFORMATION Pork Promotion, Research, and Consumer Information Order Expenses and Assessments §...

  14. Understanding the assessment of psychotropic drug harms in clinical trials to improve social workers' role in medication monitoring.

    PubMed

    Hughes, Shannon; Cohen, David

    2010-04-01

    The purpose of this integrative review is to facilitate social work practitioners' understanding of how psychotropic drug harms are assessed in clinical trials and to make specific suggestions for social workers' increased involvement in detecting drug harms in their clients. The authors undertook a comprehensive review of interdisciplinary sources relating to policies, procedures, and evidence of current practices in adverse event assessment in clinical trial research. Results revealed that few guidelines exist for assessing harms in clinical drug research. Current practices consist primarily of asking research trial subjects general, open-ended questions or relying on spontaneous patient reports. These methods produce inconsistent data and are inadequate to fully inform. Meta-analysis of adverse effect rates across studies has further proven difficult and inconclusive. To address some of these limitations, the authors recommend that social workers contribute to a fuller understanding of drug effects by eliciting clients' own views of treatment effects and by monitoring ongoing effects using a concise yet comprehensive treatment emergent effects checklist. Social workers should also support policy initiatives that lessen or remove control over drug testing from pharmaceutical companies. PMID:20408352

  15. Application of electroretinography (ERG) in early drug development for assessing retinal toxicity in rats.

    PubMed

    Huang, Wenhu; Collette, Walter; Twamley, Michelle; Aguirre, Shirley A; Sacaan, Aida

    2015-12-15

    Retinal ocular toxicity is among the leading causes of drug development attrition in the pharmaceutical industry. Electroretinography (ERG) is a non-invasive functional assay used to assess neuro-retinal physiological integrity by measuring the electrical responses. To directly assess the utility of ERG, a series of studies was conducted following intravitreal and/or iv administration of pan-cyclin-dependent kinase inhibitors: AG-012,986 and AG-024,322 in rats. Both compounds have previously shown to induce retinal toxicity. Retinal injury was evaluated by ERG, histopathology and TUNEL staining. Intravitreal injection of AG-012,986 at ?10?g/eye resulted in decreases (60%) in ERG b-wave and microscopic changes of mild to moderate retinal degeneration, and at 30?g/eye led to additional ophthalmic findings. Intravenous administration of AG-012,986 daily at ?5mg/kg resulted in dose-related decreases (25 to 40%) in b-wave and sporadic to intense positive TUNEL staining. Intravitreal injection of AG-024,322 at 30?g/eye also resulted in decreases (50 to 60%) in b-wave, mild to marked retinal degeneration and mild vitreous debris. These experiments demonstrate that ERG can be used as a sensitive and reliable functional tool to evaluate retinal toxicity induced by test compounds in rats complementing other classical ocular safety measurements. PMID:26482841

  16. Assessing the drug release from nanoparticles: Overcoming the shortcomings of dialysis by using novel optical techniques and a mathematical model.

    PubMed

    Xie, Li; Beyer, Susanne; Vogel, Vitali; Wacker, Matthias G; Mäntele, Werner

    2015-07-01

    The aim of the present investigation was to develop a reliable method which can be applied to the measurement of in vitro drug release from nanocarriers. Since the limited membrane transport is one major obstacle to the assessment of drug release with dialysis techniques, the determination of this parameter was our objective. Therefore, a novel drug release automatic monitoring system (DREAMS) was designed to conduct continuous measurements during the dialysis process. Moreover, a mathematical model was used for evaluation of the experimental data. This combination of mathematical and analytical tools enabled the quantification of the total amount of free drug in the system. Eudragit(®) RS 100 nanoparticles loaded with the model compound 5,10,15,20-tetrakis(m-hydroxypheny)chlorin (mTHPC) were investigated and the drug release was continuously monitored by using a fluorescence spectrometer that is part of the setup. Free drug and drug-loaded nanoparticles were tested to discriminate between the two formulations. In addition, two types of membranes composed of different materials were evaluated and the kinetics of membrane transport was determined. The data obtained from the apparatus were further treated by a mathematical model, which yielded distinguishable release profiles between samples of different compositions. The method offers a promising option for release testing of nanoparticles. PMID:25847513

  17. Relevance of Campus Climate for Alcohol and Other Drug Use among LGBTQ Community College Students: A Statewide Qualitative Assessment

    ERIC Educational Resources Information Center

    Manning, Patricia; Pring, Lauren; Glider, Peggy

    2012-01-01

    Literature suggests that individuals who identify as LGBTQ may engage in more alcohol and other drug (AOD) use/abuse than others. Little data is available about these populations on college campuses where AOD use may be seen as part of the general campus climate and culture. This article will describe a qualitative needs assessment conducted on 10…

  18. The role of health technology assessment bodies in shaping drug development

    PubMed Central

    Ciani, Oriana; Jommi, Claudio

    2014-01-01

    The use of health technology assessment (HTA) to inform policy-making is established in most developed countries. Compared to licensing agencies, HTA agencies have different interests and, therefore, different evidence requirements. Criteria for coverage or reimbursement decisions on pharmaceutical compounds vary; however, it is common to include, as part of the HTA, a comparative effectiveness evaluation. This type of clinical data might go beyond that required for market authorization, thus creating an additional evidence gap between the regulatory and the reimbursement submission. The relevance of submissions to HTA agencies is consistently increasing in a pharmaceutical company’s perspective, as market prospects are strongly influenced by third-party payers’ coverage. In this study, we aim to describe current HTA activities with a potential impact throughout the drug development process of pharmaceuticals, with a comparative emphasis on the systems in place in Italy and in the UK. Based on an extensive literature and website review, we identified three major classes of HTA activities, beyond mainstream HTA, with the potential to influence the drug development program: 1) horizon scanning and early HTA; 2) bipartite and tripartite early dialogue between manufacturers, regulators, and HTA assessors; and 3) managed market entry agreements. From early stages of clinical research up to postauthorization studies, there is a trend toward increased collaboration between parties, anticipation of market access evidence collection, and postmarketing risk-sharing. Heterogeneity of HTA practices increases the complexity of the market access environment. Overall, there are signals that market access departments are gaining importance in the pharmaceutical companies, but there is still a lack of evidence and reporting on how the increasing relevance of HTA has reshaped the way clinical development is designed and managed. PMID:25419117

  19. Transmission Assessment Surveys (TAS) to Define Endpoints for Lymphatic Filariasis Mass Drug Administration: A Multicenter Evaluation

    PubMed Central

    Chu, Brian K.; Deming, Michael; Biritwum, Nana-Kwadwo; Bougma, Windtaré R.; Dorkenoo, Améyo M.; El-Setouhy, Maged; Fischer, Peter U.; Gass, Katherine; Gonzalez de Peña, Manuel; Mercado-Hernandez, Leda; Kyelem, Dominique; Lammie, Patrick J.; Flueckiger, Rebecca M.; Mwingira, Upendo J.; Noordin, Rahmah; Offei Owusu, Irene; Ottesen, Eric A.; Pavluck, Alexandre; Pilotte, Nils; Rao, Ramakrishna U.; Samarasekera, Dilhani; Schmaedick, Mark A.; Settinayake, Sunil; Simonsen, Paul E.; Supali, Taniawati; Taleo, Fasihah; Torres, Melissa; Weil, Gary J.; Won, Kimberly Y.

    2013-01-01

    Background Lymphatic filariasis (LF) is targeted for global elimination through treatment of entire at-risk populations with repeated annual mass drug administration (MDA). Essential for program success is defining and confirming the appropriate endpoint for MDA when transmission is presumed to have reached a level low enough that it cannot be sustained even in the absence of drug intervention. Guidelines advanced by WHO call for a transmission assessment survey (TAS) to determine if MDA can be stopped within an LF evaluation unit (EU) after at least five effective rounds of annual treatment. To test the value and practicality of these guidelines, a multicenter operational research trial was undertaken in 11 countries covering various geographic and epidemiological settings. Methodology The TAS was conducted twice in each EU with TAS-1 and TAS-2 approximately 24 months apart. Lot quality assurance sampling (LQAS) formed the basis of the TAS survey design but specific EU characteristics defined the survey site (school or community), eligible population (6–7 year olds or 1st–2nd graders), survey type (systematic or cluster-sampling), target sample size, and critical cutoff (a statistically powered threshold below which transmission is expected to be no longer sustainable). The primary diagnostic tools were the immunochromatographic (ICT) test for W. bancrofti EUs and the BmR1 test (Brugia Rapid or PanLF) for Brugia spp. EUs. Principal Findings/Conclusions In 10 of 11 EUs, the number of TAS-1 positive cases was below the critical cutoff, indicating that MDA could be stopped. The same results were found in the follow-up TAS-2, therefore, confirming the previous decision outcome. Sample sizes were highly sex and age-representative and closely matched the target value after factoring in estimates of non-participation. The TAS was determined to be a practical and effective evaluation tool for stopping MDA although its validity for longer-term post-MDA surveillance requires further investigation. PMID:24340120

  20. Cortical EEG oscillations and network connectivity as efficacy indices for assessing drugs with cognition enhancing potential.

    PubMed

    Ahnaou, A; Huysmans, H; Jacobs, T; Drinkenburg, W H I M

    2014-11-01

    Synchronization of electroencephalographic (EEG) oscillations represents a core mechanism for cortical and subcortical networks, and disturbance in neural synchrony underlies cognitive processing deficits in neurological and neuropsychiatric disorders. Here, we investigated the effects of cognition enhancers (donepezil, rivastigmine, tacrine, galantamine and memantine), which are approved for symptomatic treatment of dementia, on EEG oscillations and network connectivity in conscious rats chronically instrumented with epidural electrodes in different cortical areas. Next, EEG network indices of cognitive impairments with the muscarinic receptor antagonist scopolamine were modeled. Lastly, we examined the efficacy of cognition enhancers to normalize those aberrant oscillations. Cognition enhancers elicited systematic ("fingerprint") enhancement of cortical slow theta (4.5-6 Hz) and gamma (30.5-50 Hz) oscillations correlated with lower activity levels. Principal component analysis (PCA) revealed a compact cluster that corresponds to shared underlying mechanisms as compared to different drug classes. Functional network connectivity revealed consistent elevated coherent slow theta activity in parieto-occipital and between interhemispheric cortical areas. In rats instrumented with depth hippocampal CA1-CA3 electrodes, donepezil elicited similar oscillatory and coherent activities in cortico-hippocampal networks. When combined with scopolamine, the cognition enhancers attenuated the leftward shift in coherent slow delta activity. Such a consistent shift in EEG coherence into slow oscillations associated with altered slow theta and gamma oscillations may underlie cognitive deficits in scopolamine-treated animals, whereas enhanced coherent slow theta and gamma activity may be a relevant mechanism by which cognition enhancers exert their beneficial effect on plasticity and cognitive processes. The findings underscore that PCA and network connectivity are valuable tools to assess efficacy of novel therapeutic drugs with cognition enhancing potential. PMID:25181033

  1. 10 CFR 32.72 - Manufacture, preparation, or transfer for commercial distribution of radioactive drugs containing...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...abbreviation; and the quantity of radioactivity at a specified date and time. For...use instrumentation to measure the radioactivity of radioactive drugs. The licensee...measurements and calculations, the amount of radioactivity in dosages of alpha-, beta-,...

  2. 10 CFR 32.72 - Manufacture, preparation, or transfer for commercial distribution of radioactive drugs containing...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...abbreviation; and the quantity of radioactivity at a specified date and time. For...use instrumentation to measure the radioactivity of radioactive drugs. The licensee...measurements and calculations, the amount of radioactivity in dosages of alpha-, beta-,...

  3. 10 CFR 32.72 - Manufacture, preparation, or transfer for commercial distribution of radioactive drugs containing...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...abbreviation; and the quantity of radioactivity at a specified date and time. For...use instrumentation to measure the radioactivity of radioactive drugs. The licensee...measurements and calculations, the amount of radioactivity in dosages of alpha-, beta-,...

  4. 10 CFR 32.72 - Manufacture, preparation, or transfer for commercial distribution of radioactive drugs containing...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...abbreviation; and the quantity of radioactivity at a specified date and time. For...use instrumentation to measure the radioactivity of radioactive drugs. The licensee...measurements and calculations, the amount of radioactivity in dosages of alpha-, beta-,...

  5. 10 CFR 32.72 - Manufacture, preparation, or transfer for commercial distribution of radioactive drugs containing...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...abbreviation; and the quantity of radioactivity at a specified date and time. For...use instrumentation to measure the radioactivity of radioactive drugs. The licensee...measurements and calculations, the amount of radioactivity in dosages of alpha-, beta-,...

  6. Assessing the impact of tumor evolution on oncology drug development and commercialization

    E-print Network

    Sterk, Joseph P. (Sterk, Joseph Phillip)

    2011-01-01

    This thesis investigates the commercial viability of developing and commercializing targeted oncology drugs directed at a specific tumor mutation instead of all forms and mutations of a single target. While oncologic drugs ...

  7. Does mass drug administration for the integrated treatment of neglected tropical diseases really work? Assessing evidence for the control of schistosomiasis and soil-transmitted helminths in Uganda

    PubMed Central

    2011-01-01

    Background Less is known about mass drug administration [MDA] for neglected tropical diseases [NTDs] than is suggested by those so vigorously promoting expansion of the approach. This paper fills an important gap: it draws upon local level research to examine the roll out of treatment for two NTDs, schistosomiasis and soil-transmitted helminths, in Uganda. Methods Ethnographic research was undertaken over a period of four years between 2005-2009 in north-west and south-east Uganda. In addition to participant observation, survey data recording self-reported take-up of drugs for schistosomiasis, soil-transmitted helminths and, where relevant, lymphatic filariasis and onchocerciasis was collected from a random sample of at least 10% of households at study locations. Data recording the take-up of drugs in Ministry of Health registers for NTDs were analysed in the light of these ethnographic and social survey data. Results The comparative analysis of the take-up of drugs among adults revealed that although most long term residents have been offered treatment at least once since 2004, the actual take up of drugs for schistosomiasis and soil-transmitted helminths varies considerably from one district to another and often also within districts. The specific reasons why MDA succeeds in some locations and falters in others relates to local dynamics. Issues such as population movement across borders, changing food supply, relations between drug distributors and targeted groups, rumours and conspiracy theories about the 'real' purpose of treatment, subjective experiences of side effects from treatment, alternative understandings of affliction, responses to social control measures and historical experiences of public health control measures, can all make a huge difference. The paper highlights the need to adapt MDA to local circumstances. It also points to specific generalisable issues, notably with respect to health education, drug distribution and more effective use of existing public health legislation. Conclusion While it has been an achievement to have offered free drugs to so many adults, current standard practices of monitoring, evaluation and delivery of MDA for NTDs are inconsistent and inadequate. Efforts to integrate programmes have exacerbated the difficulties. Improved assessment of what is really happening on the ground will be an essential step in achieving long-term overall reduction of the NTD burden for impoverished communities. PMID:21211001

  8. Independent Orbiter Assessment (IOA): Assessment of the electrical power distribution and control subsystem, volume 1

    NASA Technical Reports Server (NTRS)

    Schmeckpeper, K. R.

    1988-01-01

    The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA first completed an analysis of the Electrical Power Distribution and Control (EPD and C) hardware, generating draft failure modes and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The IOA results were then compared to the NASA FMEA/CIL baseline with proposed Post 51-L updates included. A resolution of each discrepancy from the comparison is provided through additional analysis as required. This report documents the results of that comparison for the Orbiter EPD and C hardware. The IOA product for the EPD and C analysis consisted of 1671 failure mode analysis worksheets that resulted in 468 potential critical items being identified. Comparison was made to the proposed NASA Post 51-L baseline which consisted of FMEAs and 158 CIL items. Volume 1 contains the EPD and C subsystem description, analysis results, ground rules and assumptions, and some of the IOA worksheets.

  9. Characterization of four new designer drugs, 5-chloro-NNEI, NNEI indazole analog, ?-PHPP and ?-POP, with 11 newly distributed designer drugs in illegal products.

    PubMed

    Uchiyama, Nahoko; Matsuda, Satoru; Kawamura, Maiko; Shimokawa, Yoshihiko; Kikura-Hanajiri, Ruri; Aritake, Kosuke; Urade, Yoshihiro; Goda, Yukihiro

    2014-10-01

    Our continuous survey of illegal products in Japan revealed the new distribution of 15 designer drugs. We identified four synthetic cannabinoids, i.e., NNEI (1), 5-fluoro-NNEI (2), 5-chloro-NNEI (3) and NNEI indazole analog (4), and seven cathinone derivatives, i.e., MPHP (5), ?-PHPP (6), ?-POP (7), 3,4-dimethoxy-?-PVP (8), 4-fluoro-?-PVP (9), ?-ethylaminopentiophenone (10) and N-ethyl-4-methylpentedrone (11). We also determined LY-2183240 (12) and its 2'-isomer (13), which were reported to inhibit endocannabinoid uptake, a methylphenidate analog, 3,4-dichloromethylphenidate (14), and an MDA analog, 5-APDB (15). No chemical and pharmaceutical data for compounds 3, 4, 6 and 7 had been reported, making this the first report on these compounds. PMID:24769262

  10. Measuring topology of low-intensity DNA methylation sites for high-throughput assessment of epigenetic drug-induced effects in cancer cells

    SciTech Connect

    Gertych, Arkadiusz; Bioinformatics, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA ; Farkas, Daniel L.; Tajbakhsh, Jian

    2010-11-15

    Epigenetic anti-cancer drugs with demethylating effects have shown to alter genome organization in mammalian cell nuclei. The interest in the development of novel epigenetic drugs has increased the demand for cell-based assays to evaluate drug performance in pre-clinical studies. An imaging-based cytometrical approach that can measure demethylation effects as changes in the spatial nuclear distributions of methylated cytosine and global DNA in cancer cells is introduced in this paper. The cells were studied by immunofluorescence with a specific antibody against 5-methylcytosine (MeC), and 4,6-diamidino-2-phenylindole (DAPI) for delineation of methylated sites and global DNA in nuclei. In the preprocessing step the segmentation of nuclei in three-dimensional images (3-D) is followed by an automated assessment of nuclear DAPI/MeC patterns to exclude dissimilar entities. Next, low-intensity MeC (LIM) and low-intensity DNA (LID) sites of similar nuclei are localized and processed to obtain specific nuclear density profiles. These profiles sampled at half of the total nuclear volume yielded two parameters: LIM{sub 0.5} and LID{sub 0.5}. The analysis shows that zebularine and 5-azacytidine-the two tested epigenetic drugs introduce changes in the spatial distribution of low-intensity DNA and MeC signals. LIM{sub 0.5} and LID{sub 0.5} were significantly different (p < 0.001) in 5-azacytidine treated (n = 660) and zebularine treated (n = 496) vs. untreated (n = 649) DU145 human prostate cancer cells. In the latter case the LIM sites were predominantly found at the nuclear border, whereas treated populations showed different degrees of increase in LIMs towards the interior nuclear space, in which a large portion of heterochromatin is located. The cell-by-cell evaluation of changes in the spatial reorganization of MeC/DAPI signals revealed that zebularine is a more gentle demethylating agent than 5-azacytidine. Measuring changes in the topology of low-intensity sites can potentially be a valuable component in the high-throughput assessment of demethylation and risk of chromatin reorganization in epigenetic-drug screening tasks.

  11. Intravitreal clearance and volume of distribution of compounds in rabbits: In silico prediction and pharmacokinetic simulations for drug development.

    PubMed

    Del Amo, Eva M; Vellonen, Kati-Sisko; Kidron, Heidi; Urtti, Arto

    2015-09-01

    The aims of this research were to (1) create a curated universal database of intravitreal volumes of distribution (Vss, ivt) and clearances (CLivt) of small molecular weight compounds and macromolecules and (2) to develop quantitative structure property relationship (QSPR) and pharmacokinetic models for the estimation of vitreal drug concentrations based on the compound structure. Vss, ivt and CLivt values were determined from the available literature on intravitreal drug administration using compartmental models and curve fitting. A simple QSPR model for CLivt of small molecular weight compounds was obtained with two descriptors: LogD7.4 and hydrogen bond donor capacity. The model predicted the internal and external test sets reliably with a mean fold error of 1.50 and 1.33, respectively (Q(2)Y=0.62). For 80% of the compounds the Vss, ivt was 1.18-2.28ml; too narrow range for QSPR model building. Integration of the estimated Vss, ivt and predicted CLivt parameters into pharmacokinetic simulation models allows prediction of vitreous drug concentrations after intravitreal administration. The present work presents for the first time a database of CLivt and Vss, ivt values and the dependence of the CLivt values on the molecular structure. The study provides also useful in silico tools to investigate a priori the intravitreal pharmacokinetic profiles for intravitreally injected candidate compounds and drug delivery systems. PMID:25603198

  12. Risk assessment of distribution coefficient from 137Cs measurements.

    PubMed

    Külahci, Fatih; Sen, Zekai

    2009-02-01

    Classically distribution coefficient is defined as the ratio of solid total element concentration to surface water total concentration. This coefficient is obtained from the ion measurements in the Keban Dam, Turkey, which supplies water for domestic, irrigation and hydroelectric energy generation purposes. The measurements of 137Cs are carried out in 40 different sites and the general risk formulation and application is achieved for the distribution coefficient. The models are of exponential type and the spatial independence of the data is considered. Various charts are prepared for a set of risk levels as 5%, 10%, 20%, 25%, and 50%. PMID:18274870

  13. 75 FR 52765 - Development and Distribution of Patient Medication Information for Prescription Drugs; Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-27

    ...distribution of patient medication information (PMI) to be provided to patients who are prescribed...processes and procedures for standardizing PMI using a quality system approach for monitoring development and distribution of PMI. DATES: The public hearing will be...

  14. Drug biokinetic and toxicity assessments in rat and human primary hepatocytes and HepaRG cells within the EU-funded Predict-IV project.

    PubMed

    Mueller, Stefan O; Guillouzo, André; Hewitt, Philip G; Richert, Lysiane

    2015-12-25

    The overall aim of Predict-IV (EU-funded collaborative project #202222) was to develop improved testing strategies for drug safety in the late discovery phase. One major focus was the prediction of hepatotoxicity as liver remains one of the major organ leading to failure in drug development, drug withdrawal and has a poor predictivity from animal experiments. In this overview we describe the use and applicability of the three cell models employed, i.e., primary rat hepatocytes, primary human hepatocytes and the human HepaRG cell line, using four model compounds, chlorpromazine, ibuprofen, cyclosporine A and amiodarone. This overview described the data generated on mode of action of liver toxicity after long-term repeat-dosing. Moreover we have quantified parent compound and its distribution in various in vitro compartments, which allowed us to develop biokinetic models where we could derive real exposure concentrations in vitro. In conclusion, the complex data set enables quantitative measurements that proved the concept that we can define human relevant free and toxic exposure levels in vitro. Further compounds have to be analyzed in a broader concentration range to fully exploit these promising results for improved prediction of hepatotoxicity and hazard assessment for humans. PMID:25952325

  15. Assessing directed evolution methods for the generation of biosynthetic enzymes with potential in drug biosynthesis

    PubMed Central

    Nannemann, David P; Birmingham, William R; Scism, Robert A; Bachmann, Brian O

    2011-01-01

    To address the synthesis of increasingly structurally diverse small-molecule drugs, methods for the generation of efficient and selective biological catalysts are becoming increasingly important. ‘Directed evolution’ is an umbrella term referring to a variety of methods for improving or altering the function of enzymes using a nature-inspired twofold strategy of mutagenesis followed by selection. This article provides an objective assessment of the effectiveness of directed evolution campaigns in generating enzymes with improved catalytic parameters for new substrates from the last decade, excluding studies that aimed to select for only improved physical properties and those that lack kinetic characterization. An analysis of the trends of methodologies and their success rates from 81 qualifying examples in the literature reveals the average fold improvement for kcat (or Vmax), Km and kcat/Km to be 366-, 12- and 2548-fold, respectively, whereas the median fold improvements are 5.4, 3 and 15.6. Further analysis by enzyme class, library-generation methodology and screening methodology explores relationships between successful campaigns and the methodologies employed. PMID:21644826

  16. Toward a model of drug relapse: An assessment of the validity of the reinstatement procedure

    PubMed Central

    Epstein, David H.; Preston, Kenzie L.; Stewart, Jane; Shaham, Yavin

    2006-01-01

    Background and Rationale The reinstatement model is widely used animal model of relapse to drug addiction. However, the model’s validity is open to question. Objective We assess the reinstatement model in terms of criterion and construct validity. Research highlights and Conclusions We find that the reinstatement model has adequate criterion validity in the broad sense of the term, as evidenced by the fact that reinstatement in laboratory animals is induced by conditions reported to provoke relapse in humans. The model’s criterion validity in the narrower sense, as a medication screen, seems promising for relapse to heroin, nicotine, and alcohol. For relapse to cocaine, criterion validity has not yet established, primarily because clinical studies have examined medication’s effects on reductions in cocaine intake rather than relapse during abstinence. The model’s construct validity faces more substantial challenges and is yet to be established, but we argue that some of the criticisms of the model in this regard may have been overstated. PMID:17019567

  17. Correction: NanoSIMS analysis of an isotopically labelled organometallic ruthenium(ii) drug to probe its distribution and state in vitro.

    PubMed

    Lee, Ronald F S; Escrig, Stéphane; Croisier, Marie; Clerc-Rosset, Stéphanie; Knott, Graham W; Meibom, Anders; Davey, Curt A; Johnsson, Kai; Dyson, Paul J

    2015-11-01

    Correction for 'NanoSIMS analysis of an isotopically labelled organometallic ruthenium(ii) drug to probe its distribution and state in vitro' by Ronald F. S. Lee et al., Chem. Commun., 2015, DOI: . PMID:26507472

  18. ASSESSMENT AND IMPLICATIONS OF BACTERIAL REGROWTH IN WATER DISTRIBUTION SYSTEMS

    EPA Science Inventory

    Two water distribution systems were studied over a 1-year period. Temporal fluctuations in a number of physical, chemical and biological parameters were examined. Total and pigmented bacterial counts, total coliforms, and fecal coliforms were determined at four locations within e...

  19. URBAN WATER SYSTEM PATHOGEN ASSESSMENTS: SIGNIFICANCE OF DISTRIBUTION BIOFILMS

    EPA Science Inventory

    Quantitative microbial risk assessment (QMRA), while not new to science is now providing a fundamental role in framing water guidelines internationally as well as identifying research gaps to be filled. Professor Ashbolt has been instrumental in working QMRA concepts into WHO gui...

  20. URBAN WATER SYSTEM PATHOGEN ASSESSMENT: SIGNIFICANCE OF DISTRIBUTION BIOFILMS

    EPA Science Inventory

    Quantitative microbial risk assessment (QMRA), while not new to science is now providing a fundamental role in framing water guidelines internationally as well as identifying research gaps to be filled. Professor Ashbolt has been instrumental in working QMRA concepts into WHO gui...

  1. Condition Assessment Modeling for Distribution Systems Using Shared Frailty Analysis

    EPA Science Inventory

    Condition Assessment (CA) modeling is drawing increasing interest as a methodology for managing drinking water infrastructure. This paper develops a Cox Proportional Hazard (PH)/shared frailty model and applies it to the problem of investment in the repair and replacement of dri...

  2. 7 CFR 1230.72 - Distribution of assessments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...such State pursuant to the pork promotion program in existence in such State from July 1, 1984, to June 30, 1985, had the porcine animals subject to assessment, been produced from July 1, 1984, to June 30, 1985, and been subject to the rates...

  3. Usefulness of charge-transfer complexation for the assessment of sympathomimetic drugs: Spectroscopic properties of drug ephedrine hydrochloride complexed with some ?-acceptors

    NASA Astrophysics Data System (ADS)

    Refat, Moamen S.; Ibrahim, Omar B.; Saad, Hosam A.; Adam, Abdel Majid A.

    2014-05-01

    Recently, ephedrine (Eph) assessment in food products, pharmaceutical formulations, human fluids of athletes and detection of drug toxicity and abuse, has gained a growing interest. To provide basic data that can be used to assessment of Eph quantitatively based on charge-transfer (CT) complexation, the CT complexes of Eph with 7?,8,8?-tetracyanoquinodimethane (TCNQ), dichlorodicyanobenzoquinone (DDQ), 1,3-dinitrobenzene (DNB) or tetrabromothiophene (TBT) were synthesized and spectroscopically investigated. The newly synthesized complexes have been characterized via elemental analysis, IR, Raman, 1H NMR, and UV-visible spectroscopy. The formation constant (KCT), molar extinction coefficient (?CT) and other spectroscopic data have been determined using the Benesi-Hildebrand method and its modifications. The sharp, well-defined Bragg reflections at specific 2? angles have been identified from the powder X-ray diffraction patterns. Thermal decomposition behavior of these complexes was also studied, and their kinetic thermodynamic parameters were calculated with Coats-Redfern and Horowitz-Metzger equations.

  4. Structure-Based Prediction of Drug Distribution Across the Headgroup and Core Strata of a Phospholipid Bilayer Using Surrogate Phases

    PubMed Central

    2015-01-01

    Solvation of drugs in the core (C) and headgroup (H) strata of phospholipid bilayers affects their physiological transport rates and accumulation. These characteristics, especially a complete drug distribution profile across the bilayer strata, are tedious to obtain experimentally, to the point that even simplified preferred locations are only available for a few dozen compounds. Recently, we showed that the partition coefficient (P) values in the system of hydrated diacetyl phosphatidylcholine (DAcPC) and n-hexadecane (C16), as surrogates of the H- and C-strata of the bilayer composed of the most abundant mammalian phospholipid, PC, agree well with the preferred bilayer location of compounds. High P values are typical for lipophiles accumulating in the core, and low P values are characteristic of cephalophiles preferring the headgroups. This simple pattern does not hold for most compounds, which usually have more even distribution and may also accumulate at the H/C interface. To model complete distribution, the correlates of solvation energies are needed for each drug state in the bilayer: (1) for the H-stratum it is the DAcPC/W P value, calculated as the ratio of the C16/W and C16/DAcPC (W for water) P values; (2) for the C-stratum, the C16/W P value; (3) for the H/C interface, the P values for all plausible molecular poses are characterized using the fragment DAcPC/W and C16/W solvation parameters for the parts of the molecule embedded in the H- and C-strata, respectively. The correlates, each scaled by two Collander coefficients, were used in a nonlinear, mass-balance based model of intrabilayer distribution, which was applied to the easily measurable overall P values of compounds in the DMPC (M = myristoyl) bilayers and monolayers as the dependent variables. The calibrated model for 107 neutral compounds explains 94% of experimental variance, achieves similar cross-validation levels, and agrees well with the nontrivial, experimentally determined bilayer locations for 27 compounds. The resulting structure-based prediction system for intrabilayer distribution will facilitate more realistic modeling of passive transport and drug interactions with those integral membrane proteins, which have the binding sites located in the bilayer, such as some enzymes, influx and efflux transporters, and receptors. If only overall bilayer accumulation is of interest, the 1-octanol/W P values suffice to model the studied set. PMID:25179490

  5. Methodological approach to determine minor, considerable, and major treatment effects in the early benefit assessment of new drugs.

    PubMed

    Skipka, Guido; Wieseler, Beate; Kaiser, Thomas; Thomas, Stefanie; Bender, Ralf; Windeler, Jürgen; Lange, Stefan

    2016-01-01

    At the beginning of 2011, the early benefit assessment of new drugs was introduced in Germany with the Act on the Reform of the Market for Medicinal Products (AMNOG). The Federal Joint Committee (G-BA) generally commissions the Institute for Quality and Efficiency in Health Care (IQWiG) with this type of assessment, which examines whether a new drug shows an added benefit (a positive patient-relevant treatment effect) over the current standard therapy. IQWiG is required to assess the extent of added benefit on the basis of a dossier submitted by the pharmaceutical company responsible. In this context, IQWiG was faced with the task of developing a transparent and plausible approach for operationalizing how to determine the extent of added benefit. In the case of an added benefit, the law specifies three main extent categories (minor, considerable, major). To restrict value judgements to a minimum in the first stage of the assessment process, an explicit and abstract operationalization was needed. The present paper is limited to the situation of binary data (analysis of 2 × 2 tables), using the relative risk as an effect measure. For the treatment effect to be classified as a minor, considerable, or major added benefit, the methodological approach stipulates that the (two-sided) 95% confidence interval of the effect must exceed a specified distance to the zero effect. In summary, we assume that our approach provides a robust, transparent, and thus predictable foundation to determine minor, considerable, and major treatment effects on binary outcomes in the early benefit assessment of new drugs in Germany. After a decision on the added benefit of a new drug by G-BA, the classification of added benefit is used to inform pricing negotiations between the umbrella organization of statutory health insurance and the pharmaceutical companies. PMID:26134089

  6. Condition Assessment of Ferrous Water Transmission and Distribution Systems State of Technology Review Report

    EPA Science Inventory

    This White Paper was developed to serve as the basis for discussion at a Technology Forum on Condition Assessment of Water Transmission and Distribution Systems that was held on September 9 and 10, 2008, at Edison, NJ. It was distributed to the Forum participants for review in a...

  7. Assessment of Distributed Generation Potential in JapaneseBuildings

    SciTech Connect

    Zhou, Nan; Marnay, Chris; Firestone, Ryan; Gao, Weijun; Nishida,Masaru

    2005-05-25

    To meet growing energy demands, energy efficiency, renewable energy, and on-site generation coupled with effective utilization of exhaust heat will all be required. Additional benefit can be achieved by integrating these distributed technologies into distributed energy resource (DER) systems (or microgrids). This research investigates a method of choosing economically optimal DER, expanding on prior studies at the Berkeley Lab using the DER design optimization program, the Distributed Energy Resources Customer Adoption Model (DER-CAM). DER-CAM finds the optimal combination of installed equipment from available DER technologies, given prevailing utility tariffs, site electrical and thermal loads, and a menu of available equipment. It provides a global optimization, albeit idealized, that shows how the site energy loads can be served at minimum cost by selection and operation of on-site generation, heat recovery, and cooling. Five prototype Japanese commercial buildings are examined and DER-CAM applied to select the economically optimal DER system for each. The five building types are office, hospital, hotel, retail, and sports facility. Based on the optimization results, energy and emission reductions are evaluated. Furthermore, a Japan-U.S. comparison study of policy, technology, and utility tariffs relevant to DER installation is presented. Significant decreases in fuel consumption, carbon emissions, and energy costs were seen in the DER-CAM results. Savings were most noticeable in the sports facility (a very favourable CHP site), followed by the hospital, hotel, and office building.

  8. Illicit Drug Use Among South Korean Offenders: Assessing the Generality of Social Learning Theory.

    PubMed

    Yun, Minwoo; Kim, Eunyoung

    2015-10-01

    Since the mid-1990s, illicit drug use has become a problem in Korean society. This trend is likely due to the rapid globalization and expansion that occurred with the Internet revolution, which led to greater numbers of people socially learning about drug culture. The current study attempts to uncover criminogenic causality of such social learning about drug use by studying adult felony drug offenders in South Korea. The data used for the study were obtained from self-reported surveys, originally collected by the Korean Institution of Criminology (KIC). The final sample comprised 1,452 felony offenders convicted of illicit drug use, and their responses were analyzed with a set of multiple logistic regression tests. The current study found supportive evidence for the generalizability of social learning theory from the sample of the South Korean adult drug offenders. We argue that the current study provides additional empirical evidence that supports the generalizability of social learning theory. PMID:24752638

  9. A method for the assessment of specific energy distribution in a model tumor system

    SciTech Connect

    Noska, M.A.

    1996-12-31

    Due to the short range of alpha particles in tissue, the calculation of dose from internally deposited alpha emitters requires a detailed analysis of the microscopic distribution of the radionuclide in order to determine the spatial distribution of energy emission events and, from this, the spatial distribution of dose. In the present study, the authors used quantitative autoradiography (QAR) to assess the microdistribution of a radiolabeled monoclonal antibody (MAb) fragment in human glioma xenografts in mice.

  10. A Distributed, Collaborative Intelligent Agent System Approach for Proactive Postmarketing Drug Safety Surveillance

    PubMed Central

    Ji, Yanqing; Ying, Hao; Farber, Margo S.; Yen, John; Dews, Peter; Miller, Richard E.; Massanari, R. Michael

    2014-01-01

    Discovering unknown adverse drug reactions (ADRs) in postmarketing surveillance as early as possible is of great importance. The current approach to postmarketing surveillance primarily relies on spontaneous reporting. It is a passive surveillance system and limited by gross underreporting (<10% reporting rate), latency, and inconsistent reporting. We propose a novel team-based intelligent agent software system approach for proactively monitoring and detecting potential ADRs of interest using electronic patient records. We designed such a system and named it ADRMonitor. The intelligent agents, operating on computers located in different places, are capable of continuously and autonomously collaborating with each other and assisting the human users (e.g., the food and drug administration (FDA), drug safety professionals, and physicians). The agents should enhance current systems and accelerate early ADR identification. To evaluate the performance of the ADRMonitor with respect to the current spontaneous reporting approach, we conducted simulation experiments on identification of ADR signal pairs (i.e., potential links between drugs and apparent adverse reactions) under various conditions. The experiments involved over 275 000 simulated patients created on the basis of more than 1000 real patients treated by the drug cisapride that was on the market for seven years until its withdrawal by the FDA in 2000 due to serious ADRs. Healthcare professionals utilizing the spontaneous reporting approach and the ADRMonitor were separately simulated by decision-making models derived from a general cognitive decision model called fuzzy recognition-primed decision (RPD) model that we recently developed. The quantitative simulation results show that 1) the number of true ADR signal pairs detected by the ADRMonitor is 6.6 times higher than that by the spontaneous reporting strategy; 2) the ADR detection rate of the ADRMonitor agents with even moderate decision-making skills is five times higher than that of spontaneous reporting; and 3) as the number of patient cases increases, ADRs could be detected significantly earlier by the ADRMonitor. PMID:20007038

  11. Environmental justice, impact assessment and the politics of knowledge: The implications of assessing the social distribution of environmental outcomes

    SciTech Connect

    Walker, Gordon

    2010-09-15

    Claims of environmental injustice have increasingly become part of environmental conflicts, both explicitly through the work of environmental justice campaigning groups and implicitly through the arguments deployed about the rights and wrongs of a given situation. Such claims can centre on different notions of justice, including those concerned with questions of distribution and procedure. This paper focuses on distributional or outcome justice and explores what implications follow when the distributional concerns of environmental justice are included in the practice of impact assessment processes, including through social impact assessment (SIA). The current use of impact assessment methods in the UK is reviewed showing that although practices are evolving there is a little routine assessment of distributional inequalities. It is argued that whilst this should become part of established practice to ensure that inequalities are revealed and matters of justice are given a higher profile, the implications for conflict within decision making processes are not straightforward. On the one hand, there could be scope for conflict to be ameliorated by analysis of inequalities informing the debate between stakeholders, and facilitating the implementation of mitigation and compensation measures for disadvantaged groups. On the other hand, contestation over how evidence is produced and therefore what it shows, and disagreement as to the basis on which justice and injustice are to be determined, means that conflict may also be generated and sustained within what are essentially political and strategic settings.

  12. Assessing human vulnerability: Daytime residential distribution as a vulnerability indicator

    NASA Astrophysics Data System (ADS)

    Gokesch, Karin; Promper, Catrin; Papathoma-Köhle, Maria; Glade, Thomas

    2014-05-01

    Natural hazard risk management is based on detailed information on potential impacts of natural hazards. Especially concerning fast onset hazards such as flash floods, earthquakes but also debris flows and landslides, knowing potential hotspots of impact to both, assets and human lives is essential. This information is important for emergency management and decision making in the response phase of the disaster management cycle. Emergency managers are in need of information regarding not only the number of humans being potentially affected but also the respective vulnerability of the group affected based on characteristics such as age, income, health condition, mobility, etc. regarding a certain hazard. The analysis presented focuses on the distribution of the population, assuming a certain pattern of people in a certain radius of action. The method applied is based on a regular pattern of movement of different groups of people and a pattern of presence in certain units, e.g. schools, businesses or residential buildings. The distribution is calculated on a minimum of available data including the average household size, as well as information on building types. The study area is located in the Southwest of Lower Austria, Austria. The city of Waidhofen/Ybbs can be regarded as a regional center providing basic infrastructure, shops and schools. The high concentration of buildings combining shops and residential units leads to a high damage potential throughout the whole study area. The presented results indicate the population distribution within the study area on an average working day. It is clear that explicitly high numbers of people are located in specific buildings (e.g. schools and hospitals) which also include highly vulnerable groups especially to fast onset hazards. The results provide emergency services with the information that they need in order to intervene directly where large numbers of victims or people that need to be evacuated are located. In this way, emergency services can focus and prioritize their actions in order to save lives and reduce the number of potential victims.

  13. Application of distribution coefficients to radiological assessment models

    SciTech Connect

    Schell, W.R.; Sanchez, A.L.; Underhill, D.W.; Thomas, E.

    1985-01-01

    A field and laboratory investigation of the transport of fallout radionuclides in natural, organic rich ecosystems has been initiated. Mountain-top peat bogs in Pennsylvania, New York and Virginia were sampled by coring, dated by Pb-210 methods and measured for bomb-produced Sr-90, Pu-239, 240, and Cs-137; laboratory measurements of the distribution coefficients for Cs-137, Sr-85, Ru-106, Am-241, and Co-57 by the constant shaking method have been made. These natural terrestrial ecosystems are labeled with fallout radionuclides from nuclear weapons tests which are environmental tracers of element transport. To explain the differences between the input from fallout and the distribution of Cs-137 in peat cores, a simple ''theoretical plate'' transport model has been used. Each year of growth is assumed to be a ''theoretical plate'' and Cs-137 deposited is transferred between plates by advection and mixing processes. The annual deposition of Cs-137 occurs on the (then) uppermost layer and is proportional to the atmospheric input. The theoretical plate model finds values of the advection and mixing coefficients which give the best fit between Cs-137 profile in the bog and the atmospherically-derived Cs-137. For the three bogs tested so far, the advection coefficients indicate an upward movement of Cs-137 as well as downward transport. Values for the diffusion coefficient range from 10E/sup -7/ to 10E/sup -9/ cm/sup 2/ s/sup -1/ depending on organic content and porosity. The mass transport values from the model are compared to laboratory measurements of distribution coefficients in simulated acid rain conditions. Based on the diffusion coefficients calculated from the model, a thickness of 8 to 20 cm of peat surrounding a leaking cannister of Cs-137 would not allow the radionuclide to enter an aquifer for 300 years from a low level waste disposal site.

  14. Assessment of complex EMF exposure situations including inhomogeneous field distribution.

    PubMed

    Jokela, Kari

    2007-06-01

    Assessment of exposure to time varying electric and magnetic fields is difficult when the fields are non-uniform or very localized. Restriction of the local spatial peak value below the reference level may be too restrictive. Additional problems arise when the fields are not sinusoidal. The objective of this review is to present practical measurement procedures for realistic and not too conservative exposure assessment for verification of compliance with the exposure guidelines of ICNIRP. In most exposure situations above 10 MHz the electric field (E) is more important than the magnetic field (B). At frequencies above 500 MHz the equivalent electric field power density averaged over the body is the most relevant indicator of exposure. Assessment of specific absorption rate (SAR) is not needed when the spatial peak value does not exceed by 6 dB the average value. Below 50 MHz down to 50 Hz, the electric field induces currents flowing along the limbs and torso. The current is roughly directly proportional to the electric field strength averaged over the body. A convenient way to restrict current concentration and hot spots in the neck, ankle and wrist, is to measure the current induced in the body. This is not possible for magnetic fields. Instead, for a non-uniform magnetic field below 100 kHz the average magnetic flux density over the whole body and head are valid exposure indicators to protect the central nervous system. The first alternative to analyze exposure to non-sinusoidal magnetic fields below 100 kHz is based on the spectral comparison of each component to the corresponding reference level. In the second alternative the waveform of B or dB/dt is filtered in the time domain with a simple filter, where the attenuation varies proportionally to the reference level as a function of frequency, and the filtered peak value is compared to the peak reference level derived from the ICNIRP reference levels. PMID:17495653

  15. Rapid assessment of drug response in cancer cells using microwell array and molecular imaging

    PubMed Central

    Wang, Min S.; Luo, Zhen; Nitin, Nitin

    2015-01-01

    Selection of personalized chemotherapy regimen for individual patients has significant potential to improve chemotherapy efficacy and to reduce the deleterious effects of ineffective chemotherapy drugs. In this study, a rapid and high-throughput in vitro drug response assay was developed using a combination of microwell array and molecular imaging. The microwell array provided high-throughput analysis of drug response, which was quantified based on the reduction in intracellular uptake (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose) (2-NBDG). Using this synergistic approach, the drug response measurement was completed within 4 h, and only a couple thousand cells were needed for quantification. The broader application of this microwell molecular imaging approach was demonstrated by evaluating the drug response of two cancer cell lines, cervical (HeLa) and bladder (5637) cancer cells, to two distinct classes of chemotherapy drugs (cisplatin and paclitaxel). This approach did not require an extended cell culturing period, and the quantification of cellular drug response was 4–16 times faster compared with other cell-microarray drug response studies. Moreover, this molecular imaging approach had comparable sensitivity to traditional cell viability assays, i.e., the MTT assay and propidium iodide labeling of cellular nuclei;and similar throughput results as flow cytometry using only 1,000–2,000 cells. Given the simplicity and robustness of this microwell molecular imaging approach, it is anticipated that the assay can be adapted to quantify drug responses in a wide range of cancer cells and drugs and translated to clinical settings for a rapid in vitro drug response using clinically isolated samples. PMID:24760393

  16. In vitro, in vivo and pharmacokinetic assessment of amikacin sulphate laden polymeric nanoparticles meant for controlled ocular drug delivery

    NASA Astrophysics Data System (ADS)

    Sharma, Upendra Kumar; Verma, Amita; Prajapati, Sunil Kuamr; Pandey, Himanshu; Pandey, Avinash C.

    2015-02-01

    The rationale of current exploration was to formulate positively charged amikacin-loaded polymeric nanoparticles providing a controlled release attribute. Amikacin sulphate-loaded nanoparticles were prepared by w/o/w emulsification solvent evaporation approach succeeded by high-pressure homogenization. Two bioadhesive positively charged polymers, Eudragit® RS 100 and Eudragit® RL 100, were used in the blend, with variable ratios of drug and polymer. The formulations were assessed in terms of particle size and zeta potential. Thermal gravimetric analysis was brought out on the samples of drug, polymer and drug polymer complex. Drug loading and release attributes of the nanoparticles were scrutinized and antimicrobial activity in contrast to Staphylococcus aureus was appraised. Ocular irritation test, in vivo ocular retention study, in vivo release profile (permeation study) and in vivo antibacterial activity of polymeric nanosuspensions were executed. No rupture consequence but a lengthened drug release was contemplated from all formulations. Amikacin sulphate release from the polymeric nanoparticles reflected a better fit with Korsmeyer-Peppas model. In the course of the antibacterial activity of nanoparticles against S. aureus, formulation AE1 displays the most prominent inhibitory effect as compared with marketed formulation of amikacin sulphate.

  17. Assessment of the cytotoxicity of the photosensitizing drug BPD verteporfin using human vascular smooth muscle cells in culture.

    PubMed

    Labow, R S; Higginson, L A; Irvine, J; Keaney, M; Masters, R G; Marquis, J F; Meek, E; Mussivand, T; Walley, V M; Logan, P

    1995-11-01

    Photosensitizing drugs are selectively taken up by lipid-rich lesions such as atheromatous plaque which when exposed to light render the drugs cytotoxic. However, skin photosensitivity which persists for many weeks is a significant side effect. We investigated the cytotoxicity of a new photosensitizing drug, the benzoporphyrin derivative BPD verteporfin (Quadra Logic Technologies), which does not have this deleterious side effect. Vascular smooth muscle cells (VSMC) from normal human mammary and diseased human coronary arteries were grown in culture from explants and characterized with respect to their growth rates. The sensitivity to BPD with and without light was assessed by measuring viability after treatment. The lethal dose of drug for 50% viability loss (LD50) for BPD with light was approximately 12.5 ng/ml for mammary artery, with 52 +/- 8% cell survival (n = 6). The coronary artery VSMC from all patient sources, although differing significantly in growth rate, had a survival of 44 +/- 6% (n = 12) at the same concentration of BPD used for the mammary artery SMC (p = NS). Our results established the LD50 for BPD using human arterial sources of SMC and showed that the growth rates of the cells did not affect the cytotoxicity of the drug. PMID:8637187

  18. Characterisation of neutron fields: challenges in assessing the directional distribution.

    PubMed

    Cauwels, Vanessa; Vanhavere, Filip; Reginatto, Marcel

    2014-10-01

    The SCK·CEN has carried out neutron field characterisation campaigns at several nuclear reactors. The main goal of these measurement campaigns was to evaluate the performance of different neutron personal dosemeters. To be able to evaluate the performance of neutron personal dosemeters in terms of Hp(10), knowledge of the directional distribution is indispensable. This distribution was estimated by placing several personal dosemeters on all six sides of a slab phantom. The interpretation and conversion of this information into a reliable value for Hp(10) requires great care. The data were analysed using three methods. In the first approach, a linear interpolation was performed on three perpendicular axes. In the other two approaches, an icosahedron was used to model the angle of incidence of the neutrons and a linear interpolation or a Bayesian analysis was performed. This study describes the limitations and advantages of each of these methods and provides recommendations for their use to estimate the personal dose equivalent Hp(10) for neutron dosimetry. PMID:24966340

  19. Assessing mechanical vulnerability in water distribution networks under multiple failures

    NASA Astrophysics Data System (ADS)

    Berardi, Luigi; Ugarelli, Rita; Røstum, Jon; Giustolisi, Orazio

    2014-03-01

    Understanding mechanical vulnerability of water distribution networks (WDN) is of direct relevance for water utilities since it entails two different purposes. On the one hand, it might support the identification of severe failure scenarios due to external causes (e.g., natural or intentional events) which result into the most critical consequences on WDN supply capacity. On the other hand, it aims at figure out the WDN portions which are more prone to be affected by asset disruptions. The complexity of such analysis stems from the number of possible scenarios with single and multiple simultaneous shutdowns of asset elements leading to modifications of network topology and insufficient water supply to customers. In this work, the search for the most disruptive combinations of multiple asset failure events is formulated and solved as a multiobjective optimization problem. The higher vulnerability failure scenarios are detected as those causing the lower supplied demand due to the lower number of simultaneous failures. The automatic detection of WDN topology, subsequent to the detachments of failed elements, is combined with pressure-driven analysis. The methodology is demonstrated on a real water distribution network. Results show that, besides the failures causing the detachment of reservoirs, tanks, or pumps, there are other different topological modifications which may cause severe WDN service disruptions. Such information is of direct relevance to support planning asset enhancement works and improve the preparedness to extreme events.

  20. Assessing the distribution of sedimentary C40 carotenoids through time.

    PubMed

    French, K L; Rocher, D; Zumberge, J E; Summons, R E

    2015-03-01

    A comprehensive marine biomarker record of green and purple sulfur bacteria (GSB and PSB, respectively) is required to test whether anoxygenic photosynthesis represented a greater fraction of marine primary productivity during the Precambrian than the Phanerozoic, as current models of ocean redox evolution suggest. For this purpose, we analyzed marine rock extracts and oils from the Proterozoic to the Paleogene for C40 diagenetic products of carotenoid pigments using new analytical methods. Gas chromatography coupled with tandem mass spectrometry provides a new perspective on the temporal distributions of carotenoid biomarkers for phototrophic sulfur bacteria, specifically okenane, chlorobactane, and paleorenieratane. According to conventional paleoredox interpretations, this revised stratigraphic distribution of the GSB and PSB biomarkers implies that the shallow sunlit surface ocean (<24 m) became sulfidic more frequently in the geologic past than was previously thought. We reexamine whether there is evidence supporting a planktonic source of GSB and PSB pigments in marine systems or whether additional factors are required to explain the marine phototrophic sulfur bacteria record. To date, planktonic GSB and PSB and their pigments have been identified in restricted basins and lakes, but they have yet to be detected in the unrestricted, transiently sulfidic, marine systems. Based on modern observations, additional environmental factors, including basin restriction, microbial mats, or sediment transport, may be required to fully explain GSB and PSB carotenoids in the geologic record. PMID:25631735

  1. 10 CFR 32.21 - Radioactive drug: Manufacture, preparation, or transfer for commercial distribution of capsules...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...commercial distribution of capsules containing carbon-14 urea each for âin vivoâ diagnostic...commercial distribution of capsules containing carbon-14 urea each for “in vivo” diagnostic...capsules containing 37 kBq (1 µCi) carbon-14 urea (allowing for nominal...

  2. 10 CFR 32.21 - Radioactive drug: Manufacture, preparation, or transfer for commercial distribution of capsules...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...commercial distribution of capsules containing carbon-14 urea each for âin vivoâ diagnostic...commercial distribution of capsules containing carbon-14 urea each for “in vivo” diagnostic...capsules containing 37 kBq (1 µCi) carbon-14 urea (allowing for nominal...

  3. 10 CFR 32.21 - Radioactive drug: Manufacture, preparation, or transfer for commercial distribution of capsules...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...commercial distribution of capsules containing carbon-14 urea each for âin vivoâ diagnostic...commercial distribution of capsules containing carbon-14 urea each for “in vivo” diagnostic...capsules containing 37 kBq (1 µCi) carbon-14 urea (allowing for nominal...

  4. 10 CFR 32.21 - Radioactive drug: Manufacture, preparation, or transfer for commercial distribution of capsules...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...commercial distribution of capsules containing carbon-14 urea each for âin vivoâ diagnostic...commercial distribution of capsules containing carbon-14 urea each for “in vivo” diagnostic...capsules containing 37 kBq (1 µCi) carbon-14 urea (allowing for nominal...

  5. 10 CFR 32.21 - Radioactive drug: Manufacture, preparation, or transfer for commercial distribution of capsules...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...commercial distribution of capsules containing carbon-14 urea each for âin vivoâ diagnostic...commercial distribution of capsules containing carbon-14 urea each for “in vivo” diagnostic...capsules containing 37 kBq (1 µCi) carbon-14 urea (allowing for nominal...

  6. On the Use of the Beta Distribution in Probabilistic Resource Assessments

    SciTech Connect

    Olea, Ricardo A.

    2011-12-15

    The triangular distribution is a popular choice when it comes to modeling bounded continuous random variables. Its wide acceptance derives mostly from its simple analytic properties and the ease with which modelers can specify its three parameters through the extremes and the mode. On the negative side, hardly any real process follows a triangular distribution, which from the outset puts at a disadvantage any model employing triangular distributions. At a time when numerical techniques such as the Monte Carlo method are displacing analytic approaches in stochastic resource assessments, easy specification remains the most attractive characteristic of the triangular distribution. The beta distribution is another continuous distribution defined within a finite interval offering wider flexibility in style of variation, thus allowing consideration of models in which the random variables closely follow the observed or expected styles of variation. Despite its more complex definition, generation of values following a beta distribution is as straightforward as generating values following a triangular distribution, leaving the selection of parameters as the main impediment to practically considering beta distributions. This contribution intends to promote the acceptance of the beta distribution by explaining its properties and offering several suggestions to facilitate the specification of its two shape parameters. In general, given the same distributional parameters, use of the beta distributions in stochastic modeling may yield significantly different results, yet better estimates, than the triangular distribution.

  7. Human placental perfusion method in the assessment of transplacental passage of antiepileptic drugs

    SciTech Connect

    Myllynen, Paeivi . E-mail: paivi.k.myllynen@oulu.fi; Pienimaeki, Paeivi; Vaehaekangas, Kirsi

    2005-09-01

    Epilepsy is one of the most common neurological diseases, affecting about 0.5 to 1% of pregnant women. It is commonly accepted that older antiepileptic drugs bear teratogenic potential. So far, no agreement has been reached about the safest antiepileptic drug during pregnancy. It is known that nearly all drugs cross the placenta at least to some extent. Nowadays, there is very little information available of the pharmacokinetics of drugs in the feto-placental unit. Detailed information about drug transport across the placenta would be valuable for the development of safe and effective treatments. For reasons of safety, human studies on placental transfer are restricted to a limited number of drugs. Interspecies differences limit the extrapolation of animal data to humans. Several in vitro methods for the study of placental transfer have been developed over the past decades. The placental perfusion method is the only experimental method that has been used to study human placental transfer of substances in organized placental tissue. The aim of this article is to review human placental perfusion data on antiepileptic drugs. According to perfusion data, it seems that most of the antiepileptic drugs are transferred across the placenta meaning significant fetal exposure.

  8. Paclitaxel Drug-Eluting Stents in Peripheral Arterial Disease: A Health Technology Assessment

    PubMed Central

    2015-01-01

    Background Peripheral arterial disease is a condition in which atherosclerotic plaques partially or completely block blood flow to the legs. Although percutaneous transluminal angioplasty and metallic stenting have high immediate success rates in treating peripheral arterial disease, long-term patency and restenosis rates in long and complex lesions remain unsatisfactory. Objective The objective of this analysis was to evaluate the clinical effectiveness, safety, cost-effectiveness and budget impact of Zilver paclitaxel self-expanding drug-eluting stents for the treatment of de novo or restenotic lesions in above-the-knee peripheral arterial disease. Data Sources Literature searches were performed using Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid Embase, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), and EBM Reviews. For the economic review, a search filter was applied to limit search results to economics-related literature. Data sources for the budget impact analysis included expert opinion, published literature, and Ontario administrative data. Review Methods Systematic reviews, meta-analyses, randomized controlled trials, and observational studies were included in the clinical effectiveness review, and full economic evaluations were included in the economic literature review. Studies were included if they examined the effect of Zilver paclitaxel drug-eluting stents in de novo or restenotic lesions in above-the-knee arteries. For the budget impact analysis, 3 scenarios were constructed based on different assumptions. Results One randomized controlled trial reported a significantly higher patency rate with Zilver paclitaxel drug-eluting stents for lesions ? 14 cm than with angioplasty or bare metal stents. One observational study showed no difference in patency rates between Zilver paclitaxel drug-eluting stents and paclitaxel drug-coated balloons. Zilver paclitaxel drug-eluting stents were associated with a significantly higher event-free survival rate than angioplasty, but the event-free survival rate was similar for Zilver paclitaxel drug-eluting stents and paclitaxel drug-coated balloons. No economic evaluations compared Zilver paclitaxel drug-eluting stents with bare metal stents or angioplasty for peripheral arterial disease. A budget impact analysis showed that the cost savings associated with funding of Zilver paclitaxel drug-eluting stents would be $470,000 to $640,000 per year, assuming that the use of the Zilver paclitaxel drug-eluting stent was associated with a lower risk of subsequent revascularization. Conclusions Based on evidence of low to moderate quality, Zilver paclitaxel drug-eluting stents were associated with a higher patency rate than angioplasty or bare metal stents, and with fewer adverse events than angioplasty. The effectiveness and safety of Zilver paclitaxel drug-eluting stents and paclitaxel drug-coated balloons were similar. PMID:26719778

  9. Adolescent substance-use assessment: methodological issues in the use of the ADAD (Adolescent Drug Abuse Diagnosis).

    PubMed

    Chinet, Léonie; Plancherel, Bernard; Bolognini, Monique; Holzer, Laurent; Halfon, Olivier

    2005-01-01

    During the past twenty years, various instruments have been developed for the assessment of substance use in adolescents, mainly in the United States. However, few of them have been adapted to, and validated in, French-speaking populations. Consequently, although increasing alcohol and drug use among teenagers has become a major concern, the various health and social programs developed in response to this specific problem have received little attention with regard to follow-up and outcome assessment. A standardized multidimensional assessment instrument adapted for adolescents is needed to assess the individual needs of adolescents and assign them to the most appropriate treatment setting, to provide a single measurement within and across health and social systems, and to conduct treatment outcome evaluations. Moreover, having an available instrument makes it possible to develop longitudinal and trans-cultural research studies. For this reason, a French version of the Adolescent Drug Abuse Diagnosis (ADAD) was developed and validated at the University Child and Adolescent Psychiatric Clinic in Lausanne, Switzerland. This paper aims to discuss the methodological issues that we faced when using the ADAD instrument in a 4-year longitudinal study including adolescent substance users. Methodological aspects relating to the content and format of the instrument, the assessment administration and the statistical analyses are discussed. PMID:15776986

  10. Problematizing ‘drugs’: A cultural assessment of recreational pharmaceutical use among young adults in the US

    PubMed Central

    QUINTERO, GILBERT

    2013-01-01

    Recent trends in the recreational use of pharmaceuticals among young adults in the United States highlight a number of issues regarding the problematization of drugs. Two constructions of recreational pharmaceutical use are analyzed. On the one hand, categorical frameworks based upon epidemiological data are created by institutions and media and depict recreational pharmaceutical use as illicit in unqualified, absolute terms. This is done through discourses that equate nonmedical pharmaceutical use with culturally established forms of illicit drug use. On the other hand, users’ multi-dimensional constructions of recreational pharmaceutical use emphasise social context, personal experience, and individual risk perceptions. The problematization of recreational pharmaceutical use points to intergenerational conflicts, as well as to struggles over definitions of “drug abuse” and “hard drugs”, and highlights the impact of pharmaceuticalization on recreational drug use among young people. PMID:24431478

  11. Assessing the spectral distribution on different tracking confederations

    NASA Astrophysics Data System (ADS)

    Gaspar, G.; Pó, J. M.; Magarreiro, C.; Los, A.; Brito, M. C.

    2012-10-01

    In this paper we evaluate the local spectral resource of different tracking configurations for low CPV applications, under clear sky conditions. The Spectral Model for Atmospheric Transmission of Sunshine (SMARTS) is employed to compute the solar spectrum of cloud free weather conditions, together with a model that describes the performance of different tracking configurations. The required input data to run the models are gathered for one specific clear sky day at Cabauw, The Netherlans, where the measured radiative fluxes showed a good agreement. We also calculate the spectral indicator Average Photon Energy (APE) of the SMARTS output for the different tracking configurations, to study the spectral variation during the day. Results show that the spectral distribution of a tracking system varies more than a horizontal fixed surface, and also, that the different tracking configurations can have different shifts in the incident spectrum, which provides interesting information for a low CPV systems design.

  12. Content uniformity of potent drugs in tablets.

    PubMed

    Orr, N A; Sallam, E A

    1978-12-01

    The type of distribution of low dosage drugs that occurs in batches of commercially available tablets has been examined. The uniformity of content of ethinyloestradiol tablets 10 micrograms B.P. from different sources, assessed by single tablet assay showed that three batches exhibited some positive skewness and one marked positive skewness. At the high level of dilution required, the mixing theory indicates that particles of drug must be very fine if acceptable content uniformity is to be obtained. Cohesion of particles impairs the efficiency of the mixing process. It is shown theoretically that unless the drug is dispersed into its component particles the shape of the distribution curve for the content of drug per tablet, in a batch of tablets, will be positively skewed. The relation between the tensile strength of the powdered drug and the degree of skewness of the drug content is also discussed. A positively skewed distribution for tablets containing a small amount of potent drug is unacceptable because this can lead to the presence of relatively large doses of drug in a single tablet. Where one unexpectedly high result occurs in the quality control of the content uniformity of tablets containing potent drugs it is suggested that sufficient single tablet assays be performed to allow the shape of the distribution curve to be assessed. A test for skewness should be included in compendial standards. PMID:32236

  13. Hepatitis C Viremia and Genotype Distribution among a sample of HCV-exposed Nonmedical Prescription Drug Users in Rural Appalachia

    PubMed Central

    Young, April M.; Crosby, Richard A.; Oser, Carrie B.; Leukefeld, Carl G.; Stephens, Dustin B.; Havens, Jennifer R.

    2012-01-01

    Research has demonstrated that hepatitis C (HCV) genotype distribution varies geographically and demographically. This exploratory study examines HCV viremia, viral concentration, and genotype distribution among anti-HCV positive, rural Appalachian nonmedical prescription drug users. The study population was randomly selected from a pool of 200 anti-HCV positive participants in a longitudinal study. Those randomly chosen were representative of the overall pool in terms of demographics, drug use, and other risk behaviors. Participants were tested serologically for HCV RNA, viral concentration, and genotype, and interview-administered questionnaires examined behavioral and demographic characteristics. Of the 81 participants, 69% tested RNA positive, 59% of which had viral loads exceeding 800,000 IU/mL. Approximately 66% of the RNA positive sample had genotype 1a; types 2b (16%) and 3a (13%) were less common. RNA positive participants were not significantly different than RNA negative participants demographically or behaviorally. Likewise, with the exception of education, genotype 1 participants were not significantly different than those with genotype 2 or 3. The prevalence of active HCV infection highlights a need for prevention and treatment in this population. However, the predominance of genotype 1 may present challenges due to its association with decreased responsiveness to drug treatment, although the novel class of direct-acting antivirals such as telaprevir and boceprevir offer new hope in this regard. The prevalence of genotype 1 may also foreshadow heightened burden of hepatocellular carcinoma and elevated healthcare expenditures. More research is needed to characterize HCV infection and genotype in this population. PMID:22825816

  14. Can vesicle size distributions assess eruption intensity during volcanic activity?

    NASA Astrophysics Data System (ADS)

    LaRue, A.; Baker, D. R.; Polacci, M.; Allard, P.; Sodini, N.

    2013-10-01

    We studied three-dimensional (3-D) vesicle size distributions by X-ray microtomography in scoria collected during the relatively quiescent Phase II of the April-May 2010 eruption at Eyjafjallajökull volcano, Iceland. Our goal was to compare cumulative vesicle size distributions (VSDs) measured in these samples with those found in Stromboli volcano, Italy. Stromboli was chosen because its VSDs are well-characterized and show a correlation with eruption intensity: typical Strombolian activity produces VSDs with power-law exponents near 1, whereas larger and more energetic vulcanian-type explosions and Plinian eruptions produce VSDs with power-law exponents near 1.5. The first hypothesis to be tested was whether or not the samples studied in this work would contain VSDs similar to normal Strombolian products, display higher power-law exponents, or be described by exponential functions. Before making this comparison, we tested a second hypothesis, which was that the magma-water interactions in the Eyjafjallajökull eruption might have a significant effect on the VSDs. We performed 1 bar bubble-growth experiments in which the samples were inundated with water and compared them to similar control experiments without water inundation. No significant differences between the VSDs of the two sets of experiments were found, and the second hypothesis is not supported by the experimental evidence. The Phase II Eyjafjallajökull VSDs are described by power-law exponents of ~0.8, typical of normal Strombolian eruptions, and support the first hypothesis. The comparable VSDs and behavior of Phase II of the Eyjafjallajökull 2010 eruption to Stromboli are interpreted to be a reflection of similar conduit systems in both volcanoes that are being constantly fed by the ascent of mingled/mixed magma from depth. Such behavior implies that continued activity during Phase II of the Eyjafjallajökull eruption could be expected and would have been predicted, had our VSDs been measured in real time during the eruption. However, the products studied show no peculiar feature that could herald the renewed eruption intensity observed in the following Phase III of the eruption.

  15. Cell-based systems to assess nuclear receptor activation and their use in drug development.

    PubMed

    Raucy, Judy L; Lasker, Jerome M

    2013-02-01

    The evolution of scientific information relating to the regulation of xenobiotic disposition has extended to the discovery of an intricate group of receptor systems now recognized as master regulators. These ligand-activated transcription factors are commonly designated as "nuclear receptors", and include CAR (NR1I3), PXR (NR1I2), PPAR (NR1C1, NR1C2, and NR1C3) and AhR (HLHE76). As regulators of gene expression, activation of these receptors can elicit a plethora of drug-drug interactions. The aforementioned nuclear receptors bind a wide range of structurally-unrelated ligands, such as steroid hormones, bile acids, and small drug-type molecules. A pivotal nuclear receptor with regards to regulation of drug-drug interactions is the pregnane X receptor (PXR). Gene expression profiling has demonstrated that PXR regulates over 60 human genes that are involved not only in physiological functions but also in the metabolism of xenobiotics. Moreover, chemical library screening suggests that about 10% of the compounds comprising the U. S. Food and Drug Administration 1 and 2, Sigma-Aldrich LOPAC collection, Biomol, and Tocris/TimTec bioactive collection libraries exhibit some form of PXR binding. For these reasons, efficient, rapid and economical systems have been developed to identify nuclear receptor ligands. Cell-based assays encompassing transiently and stably-transfected cells and mammalian two-hybrid systems are currently being employed by the pharmaceutical industry to screen compounds for binding to and/or activation of nuclear receptors. Overall, these systems have the ability to predict in vivo responses to receptor activation that culminate in drug-drug interactions and adverse drug effects. PMID:23330544

  16. Considerations for assessing the potential effects of antidiabetes drugs on cardiac ventricular repolarization: A report from the Cardiac Safety Research Consortium.

    PubMed

    Heller, Simon; Darpö, Börje; Mitchell, Malcolm I; Linnebjerg, Helle; Leishman, Derek J; Mehrotra, Nitin; Zhu, Hao; Koerner, John; Fiszman, Mónica L; Balakrishnan, Suchitra; Xiao, Shen; Todaro, Thomas G; Hensley, Ingrid; Guth, Brian D; Michelson, Eric L; Sager, Philip

    2015-07-01

    Thorough QT studies conducted according to the International Council on Harmonisation E14 guideline are required for new nonantiarrhythmic drugs to assess the potential to prolong ventricular repolarization. Special considerations may be needed for conducting such studies with antidiabetes drugs as changes in blood glucose and other physiologic parameters affected by antidiabetes drugs may prolong the QT interval and thus confound QT/corrected QT assessments. This review discusses potential mechanisms for QT/corrected QT interval prolongation with antidiabetes drugs and offers practical considerations for assessing antidiabetes drugs in thorough QT studies. This article represents collaborative discussions among key stakeholders from academia, industry, and regulatory agencies participating in the Cardiac Safety Research Consortium. It does not represent regulatory policy. PMID:26093861

  17. Therapeutic drug monitoring for triazoles: A needs assessment review and recommendations from a Canadian perspective

    PubMed Central

    Laverdiere, Michel; Bow, Eric J; Rotstein, Coleman; Autmizguine, Julie; Broady, Raewyn; Garber, Gary; Haider, Shariq; Hussaini, Trana; Husain, Shahid; Ovetchkine, Philippe; Seki, Jack T; Théorêt, Yves

    2014-01-01

    Invasive fungal infections cause significant morbidity and mortality in patients with concomitant underlying immunosuppressive diseases. The recent addition of new triazoles to the antifungal armamentarium has allowed for extended-spectrum activity and flexibility of administration. Over the years, clinical use has raised concerns about the degree of drug exposure following standard approved drug dosing, questioning the need for therapeutic drug monitoring (TDM). Accordingly, the present guidelines focus on TDM of triazole antifungal agents. A review of the rationale for triazole TDM, the targeted patient populations and available laboratory methods, as well as practical recommendations based on current evidence from an extended literature review are provided in the present document. PMID:25587296

  18. Computational assessment of drug-induced effects on the electrocardiogram: from ion channel to body surface potentials

    PubMed Central

    Zemzemi, Nejib; Bernabeu, Miguel O; Saiz, Javier; Cooper, Jonathan; Pathmanathan, Pras; Mirams, Gary R; Pitt-Francis, Joe; Rodriguez, Blanca

    2013-01-01

    Background and Purpose Understanding drug effects on the heart is key to safety pharmacology assessment and anti-arrhythmic therapy development. Here our goal is to demonstrate the ability of computational models to simulate the effect of drug action on the electrical activity of the heart, at the level of the ion-channel, cell, heart and ECG body surface potential. Experimental Approach We use the state-of-the-art mathematical models governing the electrical activity of the heart. A drug model is introduced using an ion channel conductance block for the hERG and fast sodium channels, depending on the IC50 value and the drug dose. We simulate the ECG measurements at the body surface and compare biomarkers under different drug actions. Key Results Introducing a 50% hERG-channel current block results in 8% prolongation of the APD90 and 6% QT interval prolongation, hERG block does not affect the QRS interval. Introducing 50% fast sodium current block prolongs the QRS and the QT intervals by 12% and 5% respectively, and delays activation times, whereas APD90 is not affected. Conclusions and Implications Both potassium and sodium blocks prolong the QT interval, but the underlying mechanism is different: for potassium it is due to APD prolongation; while for sodium it is due to a reduction of electrical wave velocity. This study shows the applicability of in silico models for the investigation of drug effects on the heart, from the ion channel to the ECG-based biomarkers. PMID:22946617

  19. Preclinical Development of an anti-5T4 Antibody-Drug Conjugate: Pharmacokinetics in Mice, Rats, and NHP and Tumor/Tissue Distribution in Mice.

    PubMed

    Leal, Mauricio; Wentland, JoAnn; Han, Xiaogang; Zhang, Yanhua; Rago, Brian; Duriga, Nicole; Spriggs, Franklin; Kadar, Eugene; Song, Wei; McNally, James; Shakey, Quazi; Lorello, Leslie; Lucas, Judy; Sapra, Puja

    2015-11-18

    The pharmacokinetics of an antibody (huA1)-drug (auristatin microtubule disrupting MMAF) conjugate, targeting 5T4-expressing cells, were characterized during the discovery and development phases in female nu/nu mice and cynomolgus monkeys after a single dose and in S-D rats and cynomolgus monkeys from multidose toxicity studies. Plasma/serum samples were analyzed using an ELISA-based method for antibody and conjugate (ADC) as well as for the released payload using an LC-MS/MS method. In addition, the distribution of the Ab, ADC, and released payload (cys-mcMMAF) was determined in a number of tissues (tumor, lung, liver, kidney, and heart) in two tumor mouse models (H1975 and MDA-MB-361-DYT2 models) using similar LBA and LC-MS/MS methods. Tissue distribution studies revealed preferential tumor distribution of cys-mcMMAF and its relative specificity to the 5T4 target containing tissue (tumor). Single dose studies suggests lower CL values at the higher doses in mice, although a linear relationship was seen in cynomolgus monkeys at doses from 0.3 to 10 mg/kg with no evidence of TMDD. Evaluation of DAR (drug-antibody ratio) in cynomolgus monkeys (at 3 mg/kg) indicated that at least half of the payload was still on the ADC 1 to 2 weeks after IV dosing. After multiple doses, the huA1 and conjugate data in rats and monkeys indicate that exposure (AUC) increases with increasing dose in a linear fashion. Systemic exposure (as assessed by Cmax and AUC) of the released payload increased with increasing dose, although exposure was very low and its pharmacokinetics appeared to be formation rate limited. The incidence of ADA was generally low in rats and monkeys. We will discuss cross species comparison, relationships between the Ab, ADC, and released payload exposure after multiple dosing, and insights into the distribution of this ADC with a focus on experimental design as a way to address or bypass apparent obstacles and its integration into predictive models. PMID:26180901

  20. Assessment of ion-selective optical nanosensors for drug screening applications

    E-print Network

    Yun, Hannah

    2007-01-01

    Ion channels represent an important category of drug targets. They play a significant role in numerous physiological functions, from membrane excitation and signaling to fluid absorption and secretion. An ion-channel assay ...

  1. Cationic Albumin Nanoparticles for Enhanced Drug Delivery to Treat Breast Cancer: Preparation and In Vitro Assessment

    E-print Network

    Abbasi, Sana; Paul, Arghya; Shao, Wei; Prakash, Satya

    2012-01-01

    Most anticancer drugs are greatly limited by the serious side effects that they cause. Doxorubicin (DOX) is an antineoplastic agent, commonly used against breast cancer. However, it may lead to irreversible cardiotoxicity, ...

  2. Distributional Assumptions in Educational Assessments Analysis: Normal Distributions versus Generalized Beta Distribution in Modeling the Phenomenon of Learning

    ERIC Educational Resources Information Center

    Campos, Jose Alejandro Gonzalez; Moraga, Paulina Saavedra; Del Pozo, Manuel Freire

    2013-01-01

    This paper introduces the generalized beta (GB) model as a new modeling tool in the educational assessment area and evaluation analysis, specifically. Unlike normal model, GB model allows us to capture some real characteristics of data and it is an important tool for understanding the phenomenon of learning. This paper develops a contrast with the…

  3. The comparative accuracy of performance distribution assessments versus conventional summary judgment assessments 

    E-print Network

    McMonagle, David Coglan

    2002-01-01

    of two videotaped assessment center participants. One group (N = 88) reported frequency information, while the other group (N = 115) provided traditional summary judgments of performance. Accuracy indices (Kane, 2000), comparing the participants...

  4. The Differences across Distributed Leadership Practices by School Position According to the Comprehensive Assessment of Leadership for Learning (CALL)

    ERIC Educational Resources Information Center

    Blitz, Mark H.; Modeste, Marsha

    2015-01-01

    The Comprehensive Assessment of Leadership for Learning (CALL) is a multi-source assessment of distributed instructional leadership. As part of the validation of CALL, researchers examined differences between teacher and leader ratings in assessing distributed leadership practices. The authors utilized a t-test for equality of means for the…

  5. Studies on the drug resistance profile of Enterococcus faecium distributed from poultry retailers to hospitals.

    PubMed

    Limayem, Alya; Donofrio, Robert Scott; Zhang, Chao; Haller, Edward; Johnson, Michael G

    2015-11-01

    The multidrug resistant Enterococcus faecium (MEF) strains originating from farm animals are proliferating at a substantial pace to impact downstream food chains and could reach hospitals. This study was conducted to elucidate the drug susceptibility profile of MEF strains collected from poultry products in Ann Arbor, MI area and clinical settings from Michigan State Lab and Moffitt Cancer Center (MCC) in Florida. Presumptive positive Enterococcus isolates at species level were identified by Matrix Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) analysis. The antibiotic susceptibility profile for both poultry and clinical strains was determined by the Thermo Scientific's Sensititre conform to the National Committee for Clinical Laboratory Standards (NCCLS) and validated via quantitative real-time PCR (qPCR) methods. Out of 50 poultry samples (Turkey: n = 30; Chicken: n = 20), 36 samples were positive for Enterococcus species from which 20.83% were identified as E. faecium. All the E. faecium isolates were multidrug resistant and displayed resistance to the last alternative drug, quinupristin/dalfopristin (QD) used to treat vancomycin resistant E. faecium (VRE) in hospitals. Results indicate the presence of MEF strains in food animals and clinical settings that are also resistant to QD. PMID:26357893

  6. Application of Hansen solubility parameters for understanding and prediction of drug distribution in microspheres.

    PubMed

    Vay, Kerstin; Scheler, Stefan; Friess, Wolfgang

    2011-09-15

    In an emulsion solvent extraction/evaporation process for the preparation of microspheres the employed solvents have a tremendous influence on the characteristics of the resulting particles. Nevertheless the solvent selection is often based on empirical data rather than on calculated values. The purpose of this investigation was to use the concept of solubility parameters for interpretation and improved understanding of solvent effects in the process of microparticle preparation. Partial solubility parameters of 3-{2-[4-(6-Fluor-1,2-benzisoxazol-3-yl)piperidino]ethyl}-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-on, which was used as a model drug, were determined experimentally using an extended Hansen regression model. Poly(lactide-co-glycolide) microparticles were prepared with an emulsion solvent removal process employing methylene chloride and its mixtures with benzyl alcohol and n-butanol. It could be shown, that the encapsulation efficiency was influenced by the change of the solvent composition during the extraction process. Furthermore the solvent selection had an essential influence on the morphological state of the drug and it could be shown and explained, that by a decrease of the dissolving power a completely amorphous product was obtained. PMID:21745557

  7. Gold island films as biocompatible SERS substrates for imaging of the intracellular distribution of anticancer drugs

    NASA Astrophysics Data System (ADS)

    Sockalingum, Ganesh D.; Beljebbar, Abdelilah; Morjani, Hamid; Manfait, Michel

    1998-04-01

    Highly reproducible and stable surface gold island films exhibiting long-range enhancement have been investigated and characterized as compatible for biological systems. These surface-enhanced Raman scattering (SERS) substrates allowed the non-invasive detection of micromolar concentrations of antitumor drugs using red and near-infrared excitations. Thus, good quality SERS spectra of dimethylcrocetin (DMCRT) in a single living HL60 cell have been recorded on these substrates using red excitation, without any noticeable perturbation of the cell integrity. Comparison of these spectra with FT-Raman data obtained in HL60 cells on one hand, and with FT-SERS data of the DMCRT-retinoic acid receptor (RAR) complex on the other, shows practically the same spectral profiles. However, it should be noted that with the red laser the spectrum gives additional information on the cellular components. Similarity between the signal of DMCRT-treated K562 cells and the free drug is explained by either an absence of RAR in this cell line or a lack of binding.

  8. COMPARISON OF IN VITRO METHODS AND THE IN VIVO METABOLISM OF LINDANE FOR ASSESSING THE EFFECTS OF REPEATED ADMINISTRATION OF ETHANOL ON HEPATIC DRUG METABOLISM

    EPA Science Inventory

    In vitro methods of assessing alterations in drug metabolism and the measurement of lindane metabolites in urine were compared for their ability to determine the influence of ethanol on drug metabolism. Ethanol was administered to young adult female rats daily for seven days at d...

  9. Similarity between obesity and drug addiction as assessed by neurofunctional imaging: a concept review.

    PubMed

    Wang, Gene-Jack; Volkow, Nora D; Thanos, Panayotis K; Fowler, Joanna S

    2004-01-01

    Overeating in obese individuals shares similarities with the loss of control and compulsive drug taking behavior observed in drug-addicted subjects. The mechanism of these behaviors is not well understood. Our prior studies with positron emission tomography (PET) in drug-addicted subjects documented reductions in striatal dopamine (DA) D2 receptors. In pathologically obese subjects, we found reductions in striatal DA D2 receptors similar to that in drug-addicted subjects. Moreover, DA D2 receptor levels were found to have an inverse relationship to the body mass index of the obese subjects. We postulated that decreased levels of DA D2 receptors predisposed subjects to search for reinforcers; in the case of drug-addicted subjects for the drug and in the case of the obese subjects for food as a means to temporarily compensate for a decreased sensitivity of DA D2 regulated reward circuits. Understanding the mechanism in food intake will help to suggest strategies for the treatment of obesity. PMID:15256343

  10. Identification of phototransformation products of the antiepileptic drug gabapentin: Biodegradability and initial assessment of toxicity.

    PubMed

    Herrmann, Manuel; Menz, Jakob; Olsson, Oliver; Kümmerer, Klaus

    2015-11-15

    The anticonvulsant drug Gabapentin (GAB) is used for the treatment of various diseases (e.g. epilepsy, bipolar disorder, neuropathic pain) and is being consumed in high amounts. As GAB is not metabolized and shows a weak elimination in sewage treatment plants (STPs), it has been detected in surface water and even in raw potable water. Moreover, the confirmed teratogenic effects of GAB indicate the need for further investigations regarding options for the elimination of GAB in the water cycle. Little is known about the behavior of GAB during treatment with UV light, which is normally used for the disinfection of potable water and discussed for advanced wastewater treatment. In this study, GAB was exposed to polychromatic UV irradiation at different initial concentrations in aqueous solution. Afterwards the structures of the resulting phototransformation products (PTPs) were identified and elucidated by means of high-resolution mass spectrometry. GAB and photolytic mixtures were submitted to the Closed Bottle Test (CBT; OECD 301 D) to assess biodegradability. Furthermore, the toxicity of GAB and its photolytic mixtures was initially addressed on screening level using a modified luminescent bacteria test (LBT) and the umu-test (ISO/FDIS 13829). Environmentally realistic concentrations of GAB were disclosed by predicting STP influent concentrations (24.3 and 23.2 ?g L(-1)). GAB with initial concentration of 100 mg L(-1) was eliminated by 80% after 128 min of direct UV irradiation, but just 9% of non-purgeable organic carbon (NPOC) was removed indicating the formation of dead-end transformation products (TPs). Structures of different PTPs were elucidated and several identical PTPs could also be identified at lower initial treatment concentrations (20 mg L(-1), 5 mg L(-1), 1 mg L(-1) and 0.1 mg L(-1)). GAB was classified as not readily biodegradable. Moreover, photo treatment did not result in better biodegradable PTPs. With increasing UV treatment duration, photolytic mixtures of GAB showed an increased inhibition of both, the bacterial luminescence emission as well as the growth in the modified LBT. In the umu-test no significant induction of the umuC gene as an indicator of genotoxicity was observed. Our results show that UV irradiation of GAB containing water would lead to the formation of recalcitrant PTPs. Considering that GAB was found in raw drinking water, the formation of toxic PTPs during drinking water treatment with UV light might be possible. Therefore, further studies should be conducted regarding the fate and effects on human health and the environment of GAB and the PTPs identified within this study. PMID:26281960

  11. Down-regulation of Hsp90 could change cell cycle distribution and increase drug sensitivity of tumor cells

    PubMed Central

    Liu, Xian-Ling; Xiao, Bing; Yu, Zhao-Cai; Guo, Jian-Cheng; Zhao, Qing-Chuan; Xu, Li; Shi, Yong-Quan; Fan, Dai-Ming

    1999-01-01

    AIM: To construct Hsp90 antisense RNA eukaryotic expression vector, transfect it into SGC7901 and SGC7901/VCR of MDR-type human gastric cancer cell lines, HCC7402 of human hepatic cancer and Ec109 of human esophageal cancer cell lines, and to study the cell cycle distribution of the gene transected cells and their response to chemotherapeutic drugs. METHODS: A 1.03 kb cDNA sequence of Hsp90? was obtained from the primary plasmid phHSP90 by EcoRI and BamHI nuclease diges tion and was cloned to the EcoRI and BamHI site of the pcDNA by T4DNA ligase and an antisense orientation of Hsp90? expression vector was constructed. The constructs were transfected with lipofectamine and positive clones were selected with G418. The expression of RNA was determined with dot blotting and RNase protecti on assay, and the expression of Hsp90 protein determined with western blot. Cell cycle distribution of the transfectants was analyzed with flow cytometry, and the drug sensitivity of the transfectants to Adriamycin (ADR), vincrinstine (VCR), mitomycin (MMC ) and cyclophosphamide (CTX) with MTT and intracellular drug concentration of the transfectants was determined with flow cytometry. RESULTS: In EcoRI and BamHI restriction analysis, the size and the direction of the cloned sequence of Hsp90? remained what had been designed and the gene constructs were named pcDNA-Hsp90. AH-SGC790, AH-SGC7901/VCR, AH-HCC7402 and AH-Ec109 cell clones all expressed Hsp90 anti-sense RNA. The expression of Hsp90 was down-regulated in AH-SGC7901, AH SGC7901/VCR, AH-HCC7402 and AH-Ec109 cell clones. Cell cycle distribution was changed differently. In AH-SGC7901/VCR and AH-Ec109 cells, G1 phase cells were increased; S phase and G2 phase cells were decreased as compared with their parental cell lines. In AH-SGC7901 cell, G1 phase cells were decreased, G2 phase cells increased and S phase cells were not changed, and in AH-HCC7402 cells G1, S and G2 phase cells remai ned unchanged as compared with their parental cell lines. The sensitivity of AH SGC7901, AH-SGC7901/VCR, AH-HCC7402 and AH-Ec109 to chemotherapeutic drugs, the sensitivity of AH-SGC7901/VCR to ADR, VCR, MMC and CTX the sensitivity of AH-HCC7402 to ADR and VCR, and the sensitivity of Ec109 to ADR, VCR and CTX all increased as compared with their parental cell lines. The mean fluorescence intensity of ADR in AH-SGC7901, AH-SGC7901/VCR, AH-HCC7402 and AH-Ec109 was also significantly elevated (P < 0.05). CONCLUSION: Down-regulation of Hsp90 could change cell cycle distribution and increase the drug sensitivity of tumor cells. PMID:11819430

  12. Effects of drugs on the temporal distribution of schedule-induced polydipsia in rats.

    PubMed

    Pellon, R; Blackman, D E

    1992-11-01

    Drinking was induced in food-deprived rats by a fixed-time 1-min schedule of food presentation. With three rats, d-amphetamine (0.25, 0.5, 1.0, and 2.0 mg/kg) led to a dose-related increase in licking early in the interfood intervals, the peak of the temporal distribution of licking being shifted to earlier values. These effects were seen even when d-amphetamine had no effect on overall rates of licking and drinking. With another three rats, however, diazepam (0.5, 1.0, 2.0, and 4.0 mg/kg) did not shift the peak of the temporal distribution of licks in interfood intervals, even at doses that produced small increases in overall rates of licking and drinking. However, diazepam did reduce the peak of the distributions of licks at doses that did not decrease water intake and licks per minute. PMID:1448466

  13. Hp-?-CD-voriconazole in situ gelling system for ocular drug delivery: in vitro, stability, and antifungal activities assessment.

    PubMed

    Pawar, Pravin; Kashyap, Heena; Malhotra, Sakshi; Sindhu, Rakesh

    2013-01-01

    The objective of the present study was to design ophthalmic delivery systems based on polymeric carriers that undergo sol-to-gel transition upon change in temperature or in the presence of cations so as to prolong the effect of HP- ? -CD Voriconazole (VCZ) in situ gelling formulations. The in situ gelling formulations of Voriconazole were prepared by using pluronic F-127 (PF-127) or with combination of pluronic F-68 (PF-68) and sodium alginate by cold method technique. The prepared formulations were evaluated for their physical appearance, drug content, gelation temperature (T gel), in vitro permeation studies, rheological properties, mucoadhesion studies, antifungal studies, and stability studies. All batches of in situ formulations had satisfactory pH ranging from 6.8 to 7.4, drug content between 95% and 100%, showing uniform distribution of drug. As the concentration of each polymeric component was increased, that is, PF-68 and sodium alginate, there was a decrease in T gel with increase in viscosity and mucoadhesive strength. The in vitro drug release decreased with increase in polymeric concentrations. The stability data concluded that all formulations showed the low degradation and maximum shelf life of 2 years. The antifungal efficiency of the selected formulation against Candida albicans and Asperigillus fumigatus confirmed that designed formulation has prolonged effect and retained its properties against fungal infection. PMID:23762839

  14. Rapid Assessment Response (RAR) study: drug use, health and systemic risks—Emthonjeni Correctional Centre, Pretoria, South Africa

    PubMed Central

    2014-01-01

    Background Correctional centre populations are one of the populations most at risk of contracting HIV infection for many reasons, such as unprotected sex, violence, rape and tattooing with contaminated equipment. Specific data on drug users in correctional centres is not available for the majority of countries, including South Africa. The study aimed to identify the attitudes and knowledge of key informant (KI) offender and correctional centre staff regarding drug use, health and systemic-related problems so as to facilitate the long-term planning of activities in the field of drug-use prevention and systems strengthening in correctional centres, including suggestions for the development of appropriate intervention and rehabilitation programmes. Method A Rapid Assessment Response (RAR) methodology was adopted which included observation, mapping of service providers (SP), KI interviews (staff and offenders) and focus groups (FGs). The study was implemented in Emthonjeni Youth Correctional Centre, Pretoria, South Africa. Fifteen KI staff participants were interviewed and 45 KI offenders. Results Drug use is fairly prevalent in the centre, with tobacco most commonly smoked, followed by cannabis and heroin. The banning of tobacco has also led to black-market features such as transactional sex, violence, gangsterism and smuggling in order to obtain mainly prohibited tobacco products, as well as illicit substances. Conclusion HIV, health and systemic-related risk reduction within the Correctional Service sector needs to focus on measures such as improvement of staff capacity and security measures, deregulation of tobacco products and the development and implementation of comprehensive health promotion programmes. PMID:24708609

  15. Network Capacity Assessment of CHP-based Distributed Generation on Urban Energy Distribution Networks

    NASA Astrophysics Data System (ADS)

    Zhang, Xianjun

    The combined heat and power (CHP)-based distributed generation (DG) or dis-tributed energy resources (DERs) are mature options available in the present energy market, considered to be an effective solution to promote energy efficiency. In the urban environment, the electricity, water and natural gas distribution networks are becoming increasingly interconnected with the growing penetration of the CHP-based DG. Subsequently, this emerging interdependence leads to new topics meriting serious consideration: how much of the CHP-based DG can be accommodated and where to locate these DERs, and given preexisting constraints, how to quantify the mutual impacts on operation performances between these urban energy distribution networks and the CHP-based DG. The early research work was conducted to investigate the feasibility and design methods for one residential microgrid system based on existing electricity, water and gas infrastructures of a residential community, mainly focusing on the economic planning. However, this proposed design method cannot determine the optimal DG sizing and siting for a larger test bed with the given information of energy infrastructures. In this context, a more systematic as well as generalized approach should be developed to solve these problems. In the later study, the model architecture that integrates urban electricity, water and gas distribution networks, and the CHP-based DG system was developed. The proposed approach addressed the challenge of identifying the optimal sizing and siting of the CHP-based DG on these urban energy networks and the mutual impacts on operation performances were also quantified. For this study, the overall objective is to maximize the electrical output and recovered thermal output of the CHP-based DG units. The electricity, gas, and water system models were developed individually and coupled by the developed CHP-based DG system model. The resultant integrated system model is used to constrain the DG's electrical output and recovered thermal output, which are affected by multiple factors and thus analyzed in different case studies. The results indicate that the designed typical gas system is capable of supplying sufficient natural gas for the DG normal operation, while the present water system cannot support the complete recovery of the exhaust heat from the DG units.

  16. 21 CFR 809.40 - Restrictions on the sale, distribution, and use of OTC test sample collection systems for drugs...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...test sample collection systems for drugs of abuse testing. 809.40 Section...sample collection systems for drugs of abuse testing. (a) Over-the-counter...sample collection systems for drugs of abuse testing (§ 864.3260 of...

  17. 21 CFR 809.40 - Restrictions on the sale, distribution, and use of OTC test sample collection systems for drugs...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...test sample collection systems for drugs of abuse testing. 809.40 Section...sample collection systems for drugs of abuse testing. (a) Over-the-counter...sample collection systems for drugs of abuse testing (§ 864.3260 of...

  18. 21 CFR 809.40 - Restrictions on the sale, distribution, and use of OTC test sample collection systems for drugs...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...test sample collection systems for drugs of abuse testing. 809.40 Section...sample collection systems for drugs of abuse testing. (a) Over-the-counter...sample collection systems for drugs of abuse testing (§ 864.3260 of...

  19. 21 CFR 809.40 - Restrictions on the sale, distribution, and use of OTC test sample collection systems for drugs...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...test sample collection systems for drugs of abuse testing. 809.40 Section...sample collection systems for drugs of abuse testing. (a) Over-the-counter...sample collection systems for drugs of abuse testing (§ 864.3260 of...

  20. 21 CFR 809.40 - Restrictions on the sale, distribution, and use of OTC test sample collection systems for drugs...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...test sample collection systems for drugs of abuse testing. 809.40 Section...sample collection systems for drugs of abuse testing. (a) Over-the-counter...sample collection systems for drugs of abuse testing (§ 864.3260 of...

  1. Standardization of Nomenclature and Causality Assessment in Drug-Induced Liver Injury: Summary of a Clinical Research Workshop

    PubMed Central

    Fontana, Robert J.; Seeff, Leonard B.; Andrade, Raúl J.; Björnsson, Einar; Day, Christopher P.; Serrano, Jose; Hoofnagle, Jay H.

    2013-01-01

    Idiosyncratic drug-induced liver injury (DILI) is an important but relatively infrequent cause of potentially severe acute and chronic liver injury. The aim of this clinical research workshop was to review and attempt to standardize the current nomenclature and terminology used in DILI research. Because DILI is a diagnosis of exclusion, selected elements of the medical history, laboratory tests, and previous reports were proposed to improve causality assessment. Definitions and diagnostic criteria regarding the onset of DILI, evolution of liver injury, risk factors, and mandatory testing versus optional testing for competing causes were reviewed. In addition, the role of intentional and inadvertent rechallenge, liver histology, and host genetic polymorphisms in establishing the diagnosis and prognosis of DILI were reviewed. Consensus was established regarding the need to develop a web-of-knowledge database that provides concise, reliable, and updated information on cases of liver injury due to drugs and herbal and dietary supplements. In addition, the need to develop drug-specific computerized causality assessment methods that are derived from prospectively phenotyped cases was a high priority. Proposed scales for grading DILI severity and assessing the likelihood of an agent causing DILI and written criteria for improving the reliability, accuracy, and reproducibility of expert opinion were reviewed. Finally, the unique challenges of assessing causality in children, patients with underlying liver disease, and subjects taking herbal and dietary supplements were discussed. Conclusion: Workshop participants concluded that multicenter referral networks enrolling patients with suspected DILI according to standardized methodologies are needed. These networks should also collect biological samples that may provide crucial insights into the mechanism(s) of DILI with the ultimate aim of preventing future cases of DILI. PMID:20564754

  2. GWAMAR: Genome-wide assessment of mutations associated with drug resistance in bacteria

    PubMed Central

    2014-01-01

    Background Development of drug resistance in bacteria causes antibiotic therapies to be less effective and more costly. Moreover, our understanding of the process remains incomplete. One promising approach to improve our understanding of how resistance is being acquired is to use whole-genome comparative approaches for detection of drug resistance-associated mutations. Results We present GWAMAR, a tool we have developed for detecting of drug resistance-associated mutations in bacteria through comparative analysis of whole-genome sequences. The pipeline of GWAMAR comprises several steps. First, for a set of closely related bacterial genomes, it employs eCAMBer to identify homologous gene families. Second, based on multiple alignments of the gene families, it identifies mutations among the strains of interest. Third, it calculates several statistics to identify which mutations are the most associated with drug resistance. Conclusions Based on our analysis of two large datasets retrieved from publicly available data for M. tuberculosis, we identified a set of novel putative drug resistance-associated mutations. As a part of this work, we present also an application of our tool to detect putative compensatory mutations. PMID:25559874

  3. In vitro assessment of antiretroviral drugs demonstrates potential for ototoxicity.

    PubMed

    Thein, Pru; Kalinec, Gilda M; Park, Channy; Kalinec, Federico

    2014-04-01

    Several studies have reported an increased incidence of auditory dysfunction among HIV/AIDS patients. We used auditory HEI-OC1 cells in cell viability, flow cytometry and caspases 3/7-activation studies to investigate the potential ototoxicity of fourteen HIV antiretroviral agents: Abacavir, AZT, Delavirdine, Didenosine, Efavirenz, Emtricitabine, Indinavir, Lamivudine, Nefinavir, Nevirapine, Tenofovir, Ritonavir, Stavudine and Zalcitabine, as well as combinations of these agents as used in the common anti-HIV cocktails Atripla™, Combivir™, Epzicom™, Trizivir™, and Truvada™. Our results suggested that most of the single assayed anti-HIV drugs are toxic for HEI-OC1 auditory cells. The cocktails, on the other hand, decreased auditory cells' viability with high significance, with the following severity gradient: Epzicom ? Trizivir > Atripla ? Combivir > Truvada. Interestingly, our results suggest that Trizivir- and Epzicom-induced cell death would be mediated by a caspase-independent mechanism. l-Carnitine, a natural micronutrient known to protect HEI-OC1 cells against some ototoxic drugs as well as to decrease neuropathies associated with anti-HIV treatments, increased viability of cells treated with Lamivudine and Tenofovir as well as with the cocktail Atripla, but had only minor effects on cells treated with other drugs and drug combinations. Altogether, these results suggest that some frequently used anti-HIV agents could have deleterious effects on patients' hearing, and provide arguments in favor of additional studies aimed at elucidating the potential ototoxicity of current as well as future anti-HIV drugs. PMID:24487230

  4. EO-199, a specific antagonist of antiarrhythmic drugs: Assessment by binding experiments and in vivo studies

    SciTech Connect

    Oppenheimer, E.; Harel, G.; Lipinsky, D.; Sarne, Y. )

    1991-01-01

    EO-199, a demethylated analog of the novel class I antiarrhythmic drug EO-122 was found to antagonize the antiarrhythmic activity of EO-122 and that of procainamide (Class I{sub A}). EO-199 did not block significantly the activity of a class I{sub B} antiarrhythmic agent, lidocaine. EO-199 also displaced the specific binding of ({sup 3}H)EO-122 to rate heart membranes similarly to procainamide whereas lidocaine did not. The correlation between binding experiments and pharmacological effects points to a possible subclassification of these drugs; the two chemical analogs EO-199 and EO-122, as well as procainamide (I{sub A}) but not lidocaine (I{sub B}), compete at the same site or the same state of the sodium channel. The availability of a specific antagonist might be useful for studying the mechanism of action of antiarrhythmic drugs as well as an antidote in cases of antiarrhythmics overdose intoxication.

  5. [Assessment of legal awareness regarding illicit drug use among Kraków university students].

    PubMed

    Morawska, Jowanka; Krawczyk, Elzbieta; Satora, Leszek

    2005-01-01

    Social survey is a very important source of information concerned with planing the preventive strategy and protecting against problems relevant to the use of psychoactive substances. The survey covered a group of 211 first-year students from five colleges in Kraków. The students showed weak awareness of law. The respondents are of the opinion that the rules dealing with the addiction issue have been too liberal thus far. The emphasis should be put on enforcing the anti-drug law. Otherwise it will not became a powerful weapon to counteract the drug addiction. According to the opinion of respondents the trade and delivery of drugs are highly disapproving and they require inflicting stringent punishments. The results of our analysis are the integral part of Kraków model to help addicted to psychoactive substances and of prevention activities referred to the students of colleges. PMID:16225067

  6. Zebrafish: an emerging technology for in vivo pharmacological assessment to identify potential safety liabilities in early drug discovery

    PubMed Central

    Barros, T P; Alderton, W K; Reynolds, H M; Roach, A G; Berghmans, S

    2008-01-01

    The zebrafish is a well-established model organism used in developmental biology. In the last decade, this technology has been extended to the generation of high-value knowledge on safety risks of novel drugs. Indeed, the larval zebrafish appear to combine advantages of whole organism phenotypic assays and those (rapid production of results with minimal resource engagement) of in vitro high-throughput screening techniques. Thus, if appropriately evaluated, it can offer undeniable advantages in drug discovery for identification of target and off-target effects. Here, we review some applications of zebrafish to identify potential safety liabilities, particularly before lead/candidate selection. For instance, zebrafish cardiovascular system can be used to reveal decreases in heart rate and atrial–ventricular dissociation, which may signal human ether-a-go-go-related gene (hERG) channel blockade. Another main area of interest is the CNS, where zebrafish behavioural assays have been and are further being developed into screening platforms for assessment of locomotor activity, convulsant and proconvulsant liability, cognitive impairment, drug dependence potential and impaired visual and auditory functions. Zebrafish also offer interesting possibilities for evaluating effects on bone density and gastrointestinal function. Furthermore, available knowledge of the renal system in larval zebrafish can allow identification of potential safety issues of drug candidates on this often neglected area in early development platforms. Although additional validation is certainly needed, the zebrafish is emerging as a versatile in vivo animal model to identify off-target effects that need investigation and further clarification early in the drug discovery process to reduce the current, high degree of attrition in development. PMID:18552866

  7. Distributive Fluvial Systems of the Chaco Plain - Satellite Image Assessment of Fluvial Form and Facies Distributions

    NASA Astrophysics Data System (ADS)

    Weissmann, G. S.; Hartley, A. J.; Scuderi, L.; Bhattacharyya, P.; Buehler, H.; Leleu, S.; Mather, A.

    2009-12-01

    Distributive fluvial systems (DFS) dominate fluvial deposition inside modern continental sedimentary basins and are particularly extensive in modern foreland basins. The largest of these DFS are found in the Chaco Plain, Andean Foreland Basin, South America. We use published literature, field and satellite data (Landsat, Modis, and SRTM) to construct preliminary hypotheses about the geomorphic form and fluvial facies distributions on the DFSs in this basin. The Pilcomayo River DFS extends over 700 km from apex to toe. The river enters the DFS apex as a large braided river with a bankfull channel width of 2500 m. Gravels and cobbles occur in terraces cut through the apex. At ~70-km downstream the bankfull channel width is ~2000 m and the channel is dominated by fine sand with cut banks 2-3 m high. The proximal channel belt is surrounded by floodplain sediments, however many sandy abandoned channel belts are present across the DFS, indicating a mobile channel system. Abandoned channels have a similar form to the modern channel, with minor reworking by underfit meandering streams. At ~75-km downfan, the river system diminishes in size (bankfull channel width up to 2 km but generally <1.5 km) and becomes increasingly sinuous in planform. This point appears to serve as a node for a series of recently abandoned meander belts and splays associated with discrete channels surrounded by floodplain material. At 100 km downstream the planform is highly sinuous and bankfull width has decreased to 1500 m or less. Downstream of this area abandoned meander belts dominate along the flanks of the modern channel with oxbow lakes present adjacent to the active channel. At 150 km downstream the bankfull channel belt width is 500 m or less and the river bifurcates into splays and multiple active channels which extend downstream for a further 200 km. Vegetation maps derived from Modis imagery indicate an increase in tree density around the DFS at this elevation (230 m). Along the distal portion of the DFS, a springline at ~150 m elevation separates the upper, well drained, aridisol dominated dry Chaco area of the DFS from the poorly drained wet Chaco at the toe. Channels below this line remain wet, are mud-dominated, and associated soils are hydromorphic. At the termination of the DFS the main Pilcomayo channel has a bankfull width of 120 m with sediments consisting of interbedded fine sand and mudstone. The observations from the Pilcomayo can serve as important analogues for the development of DFS in ancient foreland basin successions, particularly the recognition of the radial distribution of distinct facies types and the downstream changes in soil types associated with the spring line.

  8. An investigation into solvent-membrane interactions when assessing drug release from organic vehicles using regenerated cellulose membranes.

    PubMed

    Reid, Monica L; Brown, Marc B; Moss, Gary P; Jones, Stuart A

    2008-09-01

    The influence of organic solvents on artificial membranes when assessing drug release from topical formulations is, generally, poorly characterised yet current guidelines require no characterisation of the membrane before, during or after an experiment. Therefore, the aim of this study was to determine the effect of solvent-membrane interactions when using in-vitro Franz cell methods for the assessment of corticosteroid release and to assess compliance or otherwise with Higuchi's equation. The rate of beclometasone dipropionate monohydrate (BDP) and betamethasone 17-valerate (BMV) release across a regenerated cellulose membrane (RCM), from both saturated solutions and commercial formulations, was determined. Increasing the ratio of organic solvent, compared with aqueous phase, in the donor fluid (DF) resulted in up to a 416-fold increase in steady-state flux. Further, alterations in the receiver fluid (RF) composition caused, in some cases, 337-fold increases in flux. Analysis indicated that the RCM remained chemically unchanged, that its pore size remained constant and that no drug partitioned into the membrane, regardless of the DF or RF employed. However, it was observed that the organic solvents had a thinning effect on the RCM, resulting in enhanced flux, which was potentially due to the variation in the diffusional path length. Such findings raise issues of the veracity of data produced from any membrane release study involving a comparison of formulations with differing solvent content. PMID:18718116

  9. DEVELOPMENT OF STATISTICAL DISTRIBUTIONS OR RANGES OF STANDARD FACTORS USED IN EXPOSURE ASSESSMENTS

    EPA Science Inventory

    This document is intended to support EPA's Exposure Assessment Guidelines by providing data and information on standard factors that are used to calculate human exposure to toxic substances. tatistical distributions or ranges of values were developed for body weight, skin surface...

  10. Assessment of species diversity from species abundance distributions at different localities

    E-print Network

    Engen, Steinar

    by analysing similarities of communities of rare and endangered species of oak-living beetles in southAssessment of species diversity from species abundance distributions at different localities, Norway. We show how the spatial structure of species diversity can be analyzed using the correlation

  11. Tracer methods to assess nutrient uptake distribution in multistrata agroforestry systems

    E-print Network

    Lehmann, Johannes

    relative root activity distribution by applying the tracer to different soil depths or distances from trees, 95440 Bayreuth, Germany; 2 Federal Research Institute for Forestry and Forest Products, Hamburg, Germany, phosphorus, radioisotopes, root activity, stable isotopes Abstract Separate assessment of nutrient uptake

  12. Spatially distributed pesticide exposure assessment in the Central Valley, California, USA

    E-print Network

    Zhang, Minghua

    Spatially distributed pesticide exposure assessment in the Central Valley, California, USA Yuzhou of pesticide sources. a r t i c l e i n f o Article history: Received 24 September 2009 Received in revised level a b s t r a c t Field runoff is an important transport mechanism by which pesticides move

  13. Development of Risk Assessment Methodology for Land Application and Distribution and Marketing of Municipal Sludge

    EPA Science Inventory

    This is one of a series of reports that present methodologies for assessing the potential risks to humans or other organisms from the disposal or reuse of municipal sludge. The sludge management practices addressed by this series include land application practices, distribution a...

  14. Niche markets and evidence assessment in transition: a critical review of proposed drug reforms.

    PubMed

    Gibson, Shannon G; Lemmens, Trudo

    2014-01-01

    In response to rising demands and treatment costs, and the need to achieve better value for money in the face of tight fiscal constraints, both the National Health Service and the public drug reimbursement system are undergoing important reforms. Concurrently, the pharmaceutical sector itself is also alleged to be experiencing significant changes, perhaps most notably, a decline of the blockbuster model of drug development and a growing focus on niche market products. As pharmaceutical development strategies evolve and the resulting drug products become more complex, regulatory and policy responses must be able to evolve along with them. We explore how in numerous jurisdictions, including the UK, proposals for 'adaptive licensing' on the regulatory side and 'performance-based risk sharing agreements' on the funding side are shifting the focus of drug regulation and reimbursement towards more incremental access to new therapies and more post-market evidence generation. However, serious questions remain about how such reforms can be successfully implemented and whether they can balance demands for earlier access to promising new therapies with the need for robust evidence on safety, efficacy, and cost-effectiveness. PMID:24841527

  15. Double Jeopardy: An Assessment of the Felony Drug Provision of the Welfare Reform Act.

    ERIC Educational Resources Information Center

    Adams, Rukaiyah; Onek, David; Riker, Alissa

    In 1996 the Aid to Families with Dependent Children program was replaced with a federal block grant program called Temporary Assistance for Needy Families (TANF), which imposed time limits and work requirements on welfare recipients. The welfare legislation placed a lifetime ban on TANF and food stamp benefits for convicted drug felons, although…

  16. A Population-Based Assessment of the Drug Interaction Between Levothyroxine and Warfarin

    PubMed Central

    Pincus, D; Gomes, T; Hellings, C; Zheng, H; Paterson, JM; Mamdani, MM; Juurlink, DN

    2013-01-01

    Most drug interaction resources suggest that levothyroxine can dramatically potentiate the effect of warfarin. However, the mechanistic basis of the interaction is speculative, and little evidence supports a meaningful drug interaction. We conducted a population-based nested case–control study to examine the risk of hospitalization for hemorrhage following the initiation of levothyroxine in a cohort of 260,076 older patients receiving warfarin. In this group, we identified 10,532 case subjects hospitalized for hemorrhage and 40,595 controls. In the primary analysis, we found no association between hospitalization for hemorrhage during warfarin therapy and initiation of levothyroxine in the preceding 30 days (adjusted odds ratio 1.11, 95% confidence interval 0.67–1.86). Secondary analyses using more remote initiation of levothyroxine also found no association. These findings suggest that concerns about a clinically meaningful levothyroxine–warfarin drug interaction are not justified. Drug interaction resources that presently characterize this interaction as important should reevaluate this classification. PMID:23093318

  17. A novel assay to assess the effectiveness of antiangiogenic drugs in human breast cancer.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many cytotoxic drugs maintain antiangiogenic properties, but there are no human, tumor-based assays to evaluate their antiangiogenic potential. We used a fibrin-thrombin clot-based angiogenesis model to evaluate the angiogenic response of human breast cancer to various cytotoxic agents commonly used...

  18. A General Causal Model to Guide Alcohol, Tobacco, and Illicit Drug Prevention: Assessing the Research Evidence

    ERIC Educational Resources Information Center

    Birckmayer, Johanna D.; Holder, Harold D.; Yacoubian, George S., Jr.; Friend, Karen B.

    2004-01-01

    The problems associated with the use of alcohol, tobacco, and other drugs (ATOD) extract a significant health, social, and economic toll on American society. While the field of substance abuse prevention has made great strides during the past decade, two major challenges remain. First, the field has been disorganized and fragmented with respect to…

  19. Comparison of Estimators of Gumbel Distribution for Assessment of Seasonal and Annual Rainfall

    NASA Astrophysics Data System (ADS)

    Vivekanandan, N.

    2015-09-01

    Estimation of seasonal and annual rainfall for a river basin is of importance in planning and management of water resources projects. This study illustrates the use of six different parameter estimation methods for Gumbel distribution for assessment of seasonal and annual rainfall for Krishna and Godavari river basins. Goodness-of-Fit tests involving Anderson-Darling and Kolmogorov-Smirnov are used for checking the adequacy of fitting of Gumbel distribution to the recorded rainfall data. Model performance indicators such as correlation coefficient, model efficiency and root mean square error are used for the selection of suitable method for estimation of rainfall. The study shows that the probability weighted moments are better suited for determination of parameters of Gumbel distribution for assessment of seasonal and annual rainfall for Krishna and Godavari basins.

  20. Assessing the In Vitro Drug Release from Lipid-Core Nanocapsules: a New Strategy Combining Dialysis Sac and a Continuous-Flow System.

    PubMed

    de Andrade, Diego Fontana; Zuglianello, Carine; Pohlmann, Adriana Raffin; Guterres, Silvia Stanisçuaski; Beck, Ruy Carlos Ruver

    2015-12-01

    The in vitro assessment of drug release from polymeric nanocapsules suspensions is one of the most studied parameters in the development of drug-loaded nanoparticles. Nevertheless, official methods for the evaluation of drug release from submicrometric carriers are not available. In this work, a new approach to assess the in vitro drug release profile from drug-loaded lipid-core nanocapsules (LNC) was proposed. A continuous-flow system (open system) was designed to evaluate the in vitro drug release profiles from different LNC formulations containing prednisolone or clobetasol propionate (LNC-CP) as drug model (LNC-PD) using a homemade apparatus. The release medium was constantly renewed throughout the experiment. A dialysis bag containing 5 mL of formulation (0.5 mg mL(-1)) was maintained inside the apparatus, under magnetic stirring and controlled temperature (37°C). In parallel, studies based on the conventional dialysis sac technique (closed system) were performed. It was possible to discriminate the in vitro drug release profile of different formulations using the open system. The proposed strategy improved the sink condition, by constantly renewing the release medium, thus maintaining the drug concentration farther from the saturated concentration in the release medium. Moreover, problems due to sampling errors can be easily overcome using this semi-automated system, since the collection is done automatically without interference from the analyst. The system proposed in this paper brings important methodological and analytical advantages, becoming a promising prototype semi-automated apparatus for performing in vitro drug release studies from drug-loaded lipid-core nanocapsules and other related nanoparticle drug delivery systems. PMID:25986595

  1. Evaluation of the use of reporter antigens in an auricular lymph node assay to assess the immunosensitizing potential of drugs.

    PubMed

    Nierkens, Stefan; Nieuwenhuijsen, Leonie; Thomas, Mieke; Pieters, Raymond

    2004-05-01

    Immune-mediated idiosyncratic drug reactions are a major problem for susceptible patients, physicians, and the pharmaceutical industry. Validated screening tools to assess the immunosensitizing capacity of orally or intravenously administered pharmaceuticals are currently not available. To date, the popliteal lymph node assay (PLNA) seems the most promising tool for this purpose. The PLNA has recently been extended with the use of reporter antigens (RA) that are coinjected together with the drug of interest. The measurement of isotypes of RA-specific antibody-secreting cells (ASC) enables the distinction of sensitizing chemicals and (nonsensitizing) irritants without radio-isotopic end points. However, the use of footpad injections raises ethical concerns. Therefore, we examined the use of RA after intradermal injection into the ear of BALB/c mice and measured RA-specific ASC in the draining auricular lymph node (ALN). We show that RA-specific IgG isotype ASC numbers are very useful and sensitive parameters to identify drug-induced hypersensitivity in both PLN and ALN. However, the type 1-associated parameters (CD8(+) cells, macrophages, IFN-gamma, TNF-alpha, and IL-1 beta) that are induced in the PLN by streptozotocin were less pronounced in the ALN. Thus, the PLNA may provide more immunologically relevant information on the mechanisms of certain chemical-induced hypersensitivity reactions. The RA-ALN assay may provide an alternative for the RA-PLNA; both assays can be used to distinguish sensitizing compounds from nonsensitizing ones. PMID:14976356

  2. In vitro co-culture model of medulloblastoma and human neural stem cells for drug delivery assessment.

    PubMed

    Ivanov, Delyan P; Parker, Terry L; Walker, David A; Alexander, Cameron; Ashford, Marianne B; Gellert, Paul R; Garnett, Martin C

    2015-07-10

    Physiologically relevant in vitro models can serve as biological analytical platforms for testing novel treatments and drug delivery systems. We describe the first steps in the development of a 3D human brain tumour co-culture model that includes the interplay between normal and tumour tissue along with nutrient gradients, cell-cell and cell-matrix interactions. The human medulloblastoma cell line UW228-3 and human foetal brain tissue were marked with two supravital fluorescent dyes (CDCFDASE, Celltrace Violet) and cultured together in ultra-low attachment 96-well plates to form reproducible single co-culture spheroids (d = 600 ?m, CV% = 10%). Spheroids were treated with model cytotoxic drug etoposide (0.3-100 ?M) and the viability of normal and tumour tissue quantified separately using flow cytometry and multiphoton microscopy. Etoposide levels of 10 ?M were found to maximise toxicity to tumours (6.5% viability) while stem cells maintained a surviving fraction of 40%. The flexible cell marking procedure and high-throughput compatible protocol make this platform highly transferable to other cell types, primary tissues and personalised screening programs. The model's key anticipated use is for screening and assessment of drug delivery strategies to target brain tumours, and is ready for further developments, e.g. differentiation of stem cells to a range of cell types and more extensive biological validation. PMID:25592050

  3. Distribution of CCR5 genotypes and HLA Class I B alleles in HIV-1 infected and uninfected injecting drug users from Rio de Janeiro, Brazil.

    PubMed

    Teixeira, Sylvia Lopes Maia; Bastos, Francisco Inácio; Hacker, Mariana A; Morgado, Mariza Gonçalves

    2009-07-01

    Host genetic factors play an important role in the HIV epidemic dynamics, and have been considered in studies assessing susceptibility/resistance to HIV-1 infection as well as clinical evolution. Class I and Class II HLA alleles have been associated with the heterogeneity of HIV-1 infection susceptibility, as protective or risk factors for HIV-1 transmission. Moreover, a 32-base pair deletion in the HIV-1 CCR5 gene-coding region confers resistance to HIV-1 infection in homozygous individuals for the deleted allele. In this study, DNA samples from HIV-1 infected and uninfected injecting drug users (IDUs) from Rio de Janeiro were PCR amplified to determine CCR5 genotypes based on the presence of the CCR5Delta32 mutation and typed for the HLA-B locus, in an attempt to assess possible associations between these genetic factors and susceptibility/resistance to HIV-1 infection. The distribution of CCR5 genotypes between the two IDU groups did not differ. The homozygous mutant genotype Delta32/Delta32 was not found in this study. Except for HLA-B*45 (4.0% vs. 3.0%; p=0.04) and for B*51 (12.1% vs. 4.4%; p=0.002), no statistically significant differences were made evident when analyzing the frequencies of each HLA-B allele between Caucasian and non-Caucasian IDUs. The most frequent HLA-B alleles were B*15; B*35; B*44 and B*51. Although some differences in the allele frequencies could be observed between the two IDU groups, none of these was statistically significant. Therefore, no putative association between these genetic markers and susceptibility/resistance to HIV-1 infection could be made evident in the present study. So far, the assessment of genetic markers among the IDU population has been restricted to North American, European, and Asian studies and this report represents a pioneer descriptive study of the distribution of CCR5 genotypes and HLA-B alleles in Rio de Janeiro, Brazil. PMID:19460331

  4. Drug deposition and distribution in healthy and atherosclerotic arteries and in models of atherosclerosis following bulk or stent-based drug delivery

    E-print Network

    Vukmirovic, Neda

    2007-01-01

    Drug eluting stents have revolutionized the practice of medicine and the landscape of medical devices. Yet, more than four years after introduction clinical trial data and clinical use have still not fully clarified what ...

  5. An integrated approach to improved toxicity prediction for the safety assessment during preclinical drug development using Hep G2 cells

    SciTech Connect

    Noor, Fozia Niklas, Jens Mueller-Vieira, Ursula Heinzle, Elmar

    2009-06-01

    Efficient and accurate safety assessment of compounds is extremely important in the preclinical development of drugs especially when hepatotoxicty is in question. Multiparameter and time resolved assays are expected to greatly improve the prediction of toxicity by assessing complex mechanisms of toxicity. An integrated approach is presented in which Hep G2 cells and primary rat hepatocytes are compared in frequently used cytotoxicity assays for parent compound toxicity. The interassay variability was determined. The cytotoxicity assays were also compared with a reliable alternative time resolved respirometric assay. The set of training compounds consisted of well known hepatotoxins; amiodarone, carbamazepine, clozapine, diclofenac, tacrine, troglitazone and verapamil. The sensitivity of both cell systems in each tested assay was determined. Results show that careful selection of assay parameters and inclusion of a kinetic time resolved assay improves prediction for non-metabolism mediated toxicity using Hep G2 cells as indicated by a sensitivity ratio of 1. The drugs with EC{sub 50} values 100 {mu}M or lower were considered toxic. The difference in the sensitivity of the two cell systems to carbamazepine which causes toxicity via reactive metabolites emphasizes the importance of human cell based in-vitro assays. Using the described system, primary rat hepatocytes do not offer advantage over the Hep G2 cells in parent compound toxicity evaluation. Moreover, respiration method is non invasive, highly sensitive and allows following the time course of toxicity. Respiration assay could serve as early indicator of changes that subsequently lead to toxicity.

  6. Assessment of modulated cytostatic drug resistance by automated ?H2AX analysis.

    PubMed

    Reddig, Annika; Lorenz, Sebastian; Hiemann, Rico; Guttek, Karina; Hartig, Roland; Heiserich, Lisa; Eberle, Caroline; Peters, Vanessa; Schierack, Peter; Sack, Ulrich; Roggenbuck, Dirk; Reinhold, Dirk

    2015-08-01

    The efficacy of many chemotherapeutic agents relies on the preferential destruction of rapidly dividing cancer cells by inducing various kinds of DNA damage. The most deleterious type of DNA lesions are DNA double-strand breaks (DSB), which can be detected by immunofluorescence staining of phosphorylated histone protein H2AX (?H2AX). Furthermore, ?H2AX has been suggested as clinical pharmacodynamic biomarker in chemotherapeutic cancer treatment. A great challenge in treating neoplastic diseases is the varying response behavior among cancer patients. Thus, intrinsic or drug-induced overexpression of efflux pumps often leads to multiple drug resistance (MDR) and treatment failure. In particular, inter-individual differences in expression levels of efflux pumps, such as the permeability glycoprotein (P-gp), were shown to correlate with cancer progression. Several efficient cytostatic drugs, including the DSB-inducing agent etoposide (ETP) are known P-gp substrates. In this respect, modulation of MDR by P-gp inhibitors, like the immunosuppressives cyclosporine A (CsA) and rapamycin (Rapa) have been described. Here, we investigated the application of ?H2AX focus assay to monitor the impact of CsA and Rapa on ETP-induced cytotoxicity in human peripheral blood mononuclear cells. Evaluation of ?H2AX foci was performed by the automated fluorescence microscopy and interpretation system AKLIDES. Compared to ETP treatment alone, our results revealed a significant rise in ?H2AX focus number and percentage of DSB-positive cells after cells have been treated with ETP in the presence of either CsA or Rapa. In contrast, DSB levels of cells incubated with CsA or Rapa alone were comparable to focus number of untreated cells. Our results successfully demonstrated how automated ?H2AX analysis can be used as fast and reliable approach to monitor drug resistance and the impact of MDR modulators during treatment with DSB-inducing cytostatics.. PMID:25845327

  7. Prescription sequence symmetry analysis: assessing risk, temporality, and consistency for adverse drug reactions across datasets in five countries

    PubMed Central

    Pratt, Nicole; Chan, Esther W; Choi, Nam-Kyong; Kimura, Michio; Kimura, Tomomi; Kubota, Kiyoshi; Lai, Edward Chia-Cheng; Man, Kenneth K C; Ooba, Nobuhiro; Park, Byung-Joo; Sato, Tsugumichi; Shin, Ju-Young; Wong, Ian C K; Kao Yang, Yea-Huei; Roughead, Elizabeth E

    2015-01-01

    Background Prescription sequence symmetry analysis (PSSA) is a signal detection method for adverse drug events. Its capacity to consistently detect adverse drug events across different settings has not been tested. We aimed to determine the consistency of PSSA results for detecting positive and negative control adverse drug events across different settings. Methods Using a distributed network model, we analyzed prescription dispensing data using PSSA in Australia, Hong Kong, Japan, Korea, and Taiwan. Positive control was amiodarone and thyroxine, as a marker of amiodarone-induced hypothyroidism, a known adverse event with a clear temporal relationship to amiodarone initiation. Negative controls were amiodarone and allopurinol, as a marker of amiodarone-induced gout and thyroxine and allopurinol, as a marker of thyroxine-induced gout. Gout is not recorded as an adverse event in product information for either medicine. Adjusted sequence ratios (ASR) were calculated for each country. Pooled estimates were obtained by using the generic inverse variance method. Results A positive association was identified between amiodarone and thyroxine in all settings with a pooled ASR 2.63 (95% confidence interval (CI) 1.47–4.72). Temporal analysis showed the effect occurred within the first few weeks of treatment. No significant associations were found for the negative controls in any setting; pooled ASR were 0.76 (95%CI 0.62–0.93) and 0.98 (95%CI 0.85–1.12) for amiodarone-allopurinol and thyroxine-allopurinol, respectively. Conclusion Despite different health settings, different populations, and different patterns of medicine utilization, PSSA gave consistent estimates across countries for a well-known positive association and two negative control adverse events. © 2015 The Authors Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd. PMID:25907076

  8. Performance of an In-House Human Immunodeficiency Virus Type 1 Genotyping System for Assessment of Drug Resistance in Cuba

    PubMed Central

    Alemán, Yoan; Vinken, Lore; Kourí, Vivian; Pérez, Lissette; Álvarez, Alina; Abrahantes, Yeissel; Fonseca, Carlos; Pérez, Jorge; Correa, Consuelo; Soto, Yudira; Schrooten, Yoeri; Vandamme, Anne-Mieke; Van Laethem, Kristel

    2015-01-01

    As commercial human immunodeficiency virus type 1 drug resistance assays are expensive, they are not commonly used in resource-limited settings. Hence, a more affordable in-house procedure was set up taking into account the specific epidemiological and economic circumstances of Cuba. The performance characteristics of the in-house assay were evaluated using clinical samples with various subtypes and resistance patterns. The lower limit of amplification was determined on dilutions series of 20 clinical isolates and ranged from 84 to 529 RNA copies/mL. For the assessment of trueness, 14 clinical samples were analyzed and the ViroSeq HIV-1 Genotyping System v2.0 was used as the reference standard. The mean nucleotide sequence identity between the two assays was 98.7% ± 1.0. Additionally, 99.0% of the amino acids at drug resistance positions were identical. The sensitivity and specificity in detecting drug resistance mutations was respectively 94.1% and 99.5%. Only few discordances in drug resistance interpretation patterns were observed. The repeatability and reproducibility were evaluated using 10 clinical samples with 3 replicates per sample. The in-house test was very precise as nucleotide sequence identity among paired nucleotide sequences ranged from 98.7% to 99.9%. The acceptance criteria were met by the in-house test for all performance characteristics, demonstrating a high degree of accuracy. Subsequently, the applicability in routine clinical practice was evaluated on 380 plasma samples. The amplification success rate was 91% and good quality consensus sequences encoding the entire protease and the first 335 codons in reverse transcriptase could be obtained for 99% of the successful amplicons. The reagent cost per sample using the in-house procedure was around € 80 per genotyping attempt. Overall, the in-house assay provided good results, was feasible with equipment and reagents available in Cuba and was half as expensive as commercial assays. PMID:25671421

  9. Crosswise Model to Assess Sensitive Issues: A Study on Prevalence of Drug Abuse Among University Students of Iran

    PubMed Central

    Khosravi, Ahmad; Mousavi, Seyed Abbas; Chaman, Reza; Khosravi, Faride; Amiri, Mohammad; Shamsipour, Mansour

    2015-01-01

    Background: Precise assessment of the prevalence of illicit drug use, face various methodological challenges. Objectives: The current study aimed to investigate the prevalence of illicit drug use among students studying at Universities in Shahroud (Northeast of Iran) through crosswise method. Patients and Methods: Participants of this cross-sectional study were 1646 students at Universities in Shahroud. The data collection instrument was a questionnaire designed based on crosswise model (CM). Results: The results of the study showed that 19% of students used at least one kind of illicit drug and 14.9% used opium residue once in their life. Moreover, 3.5% of students used drug and 3% used opium residue during the last month; 40.3% of the students admitted that they fully understood the instruction of the questionnaire; 9.6% said that did not comprehend the instruction at all, and 38.1% believed they partly understood the instruction. The result showed that 33.7% of the students fully trusted, 39.8% partly trusted, and 18.4% poorly trusted this method. There was a significant relationship between comprehension level and trust in CM (P < 0.001). Conclusions: This method can be appropriate to estimate sensitive issues; however, lack of understanding the method or doubting the confidentiality of the responses can lead to bias in the results. That is to say, if the instructions are introduced better, the level of trusting the method will increase and accordingly more reliable responses can be obtained. More studies under controlled conditions are required to interpret the findings of the current study better. PMID:26405682

  10. X-ray crystallography: Assessment and validation of protein-small molecule complexes for drug discovery

    PubMed Central

    Cooper, David R.; Porebski, Przemyslaw J.; Chruszcz, Maksymilian; Minor, Wladek

    2011-01-01

    Introduction Crystallography is the key initial component for structure-based and fragment-based drug design and can often generate leads that can be developed into high potency drugs. Therefore, huge sums of money are committed based on the outcome of crystallography experiments and their interpretation. Areas covered This review discusses how to evaluate the correctness of an X-ray structure, focusing on the validation of small molecule-protein complexes. Various types of inaccuracies found within the PDB are identified and the ramifications of these errors are discussed. The reader will gain an understanding of the key parameters that need to be inspected before a structure can be used in drug discovery efforts, as well as an appreciation of the difficulties of correctly interpreting electron density for small molecules. The reader will also be introduced to methods for validating small molecules within the context of a macromolecular structure. Expert opinion One of the reasons that ligand identification and positioning, within a macromolecular crystal structure, is so difficult is that the quality of small molecules widely varies in the PDB. For this reason, the PDB can not always be considered a reliable repository of structural information pertaining to small molecules, and this makes the derivation of general principles that govern small molecule-protein interactions more difficult. PMID:21779303

  11. A risk-benefit assessment of drugs used in the management of obsessive-compulsive disorder.

    PubMed

    Carpenter, L L; McDougle, C J; Epperson, C N; Price, L H

    1996-08-01

    Established efficacy and tolerability in large multicentre controlled studies have made serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SRIs) the mainstay of monotherapy for adult obsessive-compulsive disorder (OCD). When compared with the selective serotonin reuptake inhibitors (SSRIs), the tricyclic compound clomipramine has a higher incidence of adverse effects but is well tolerated by most OCD patients and may confer the best overall antiobsessional effects. Consideration of specific adverse effect profiles, special patient population characteristics, drug interactions and relative cost of the various agents may direct clinicians in choosing the most appropriate first-line drug. Alternative agents as monotherapies have been explored, but none has consistently proven effective to date. Investigations of SRI augmentation with serotonin-enhancing agents have also failed to demonstrate substantial benefits for treatment-refractory OCD. Combination treatment with SRIs and dopamine receptor antagonist drugs appears to provide an improved response for the subpopulation of OCD patients who have comorbid 'tic-spectrum' disorders, though large-scale studies of the efficacy and tolerability of these regimens are not yet available. PMID:8884163

  12. A formalism to generate probability distributions for performance-assessment modeling

    SciTech Connect

    Kaplan, P.G.

    1990-12-31

    A formalism is presented for generating probability distributions of parameters used in performance-assessment modeling. The formalism is used when data are either sparse or nonexistent. The appropriate distribution is a function of the known or estimated constraints and is chosen to maximize a quantity known as Shannon`s informational entropy. The formalism is applied to a parameter used in performance-assessment modeling. The functional form of the model that defines the parameter, data from the actual field site, and natural analog data are analyzed to estimate the constraints. A beta probability distribution of the example parameter is generated after finding four constraints. As an example of how the formalism is applied to the site characterization studies of Yucca Mountain, the distribution is generated for an input parameter in a performance-assessment model currently used to estimate compliance with disposal of high-level radioactive waste in geologic repositories, 10 CFR 60.113(a)(2), commonly known as the ground water travel time criterion. 8 refs., 2 figs.

  13. Waste prevention in liquid detergent distribution: a comparison based on life cycle assessment.

    PubMed

    Nessi, Simone; Rigamonti, Lucia; Grosso, Mario

    2014-11-15

    The distribution of liquid detergents through self-dispensing systems has been adopted in some Italian retail stores over the last few years. By enabling the consumer to refill several times the same container, it is proposed as a less waste-generating and more environmentally friendly alternative to the traditional distribution with single-use plastic containers. For this reason, its implementation is encouraged by the national waste prevention programme recently adopted in Italy. In order to assess such claims, a life cycle assessment was carried out to evaluate whether detergent distribution through self-dispensing systems actually allows to achieve the expected reduction in waste generation and environmental impacts. The focus was on the distribution within the large-scale retail trade and on the categories of laundry detergents, fabric softeners and hand dishwashing detergents. For each of them, a set of baseline single-use scenarios were compared with two alternative waste prevention scenarios, where the detergent is distributed through self-dispensing systems. Beyond waste generation, also the Cumulative Energy Demand and thirteen midpoint-level potential impact indicators were calculated for the comparison. Results showed that a reduction in waste generation up to 98% can be achieved, depending on the category of detergent, on the baseline scenario of comparison and on the number of times the refillable container is used. A progressive reduction in the energy demand and in most of the potential impacts was also observed, starting from a minimum number of uses of the refillable container. PMID:25209251

  14. Simulation tool for assessing the release and environmental distribution of nanomaterials

    PubMed Central

    Bilal, Muhammad; Lazareva, Anastasiya; Keller, Arturo

    2015-01-01

    Summary An integrated simulation tool was developed for assessing the potential release and environmental distribution of nanomaterials (RedNano) based on a life cycle assessment approach and multimedia compartmental modeling coupled with mechanistic intermedia transport processes. The RedNano simulation tool and its web-based software implementation enables rapid “what-if?” scenario analysis, in order to assess the response of an environmental system to various release scenarios of engineered nanomaterials (ENMs). It also allows for the investigation of the impact of geographical and meteorological parameters on ENM distribution in the environment, comparison of the impact of ENM production and potential releases on different regions, and estimation of source release rates based on monitored ENM concentrations. Moreover, the RedNano simulation tool is suitable for research, academic, and regulatory purposes. Specifically, it has been used in environmental multimedia impact assessment courses at both the undergraduate and graduate levels. The RedNano simulation tool can also serve as a decision support tool to rapidly and critically assess the potential environmental implications of ENMs and thus ensure that nanotechnology is developed in a productive and environmentally responsible manner. PMID:25977865

  15. Undersampling power-law size distributions: effect on the assessment of extreme natural hazards

    USGS Publications Warehouse

    Geist, Eric L.; Parsons, Thomas E.

    2014-01-01

    The effect of undersampling on estimating the size of extreme natural hazards from historical data is examined. Tests using synthetic catalogs indicate that the tail of an empirical size distribution sampled from a pure Pareto probability distribution can range from having one-to-several unusually large events to appearing depleted, relative to the parent distribution. Both of these effects are artifacts caused by limited catalog length. It is more difficult to diagnose the artificially depleted empirical distributions, since one expects that a pure Pareto distribution is physically limited in some way. Using maximum likelihood methods and the method of moments, we estimate the power-law exponent and the corner size parameter of tapered Pareto distributions for several natural hazard examples: tsunamis, floods, and earthquakes. Each of these examples has varying catalog lengths and measurement thresholds, relative to the largest event sizes. In many cases where there are only several orders of magnitude between the measurement threshold and the largest events, joint two-parameter estimation techniques are necessary to account for estimation dependence between the power-law scaling exponent and the corner size parameter. Results indicate that whereas the corner size parameter of a tapered Pareto distribution can be estimated, its upper confidence bound cannot be determined and the estimate itself is often unstable with time. Correspondingly, one cannot statistically reject a pure Pareto null hypothesis using natural hazard catalog data. Although physical limits to the hazard source size and by attenuation mechanisms from source to site constrain the maximum hazard size, historical data alone often cannot reliably determine the corner size parameter. Probabilistic assessments incorporating theoretical constraints on source size and propagation effects are preferred over deterministic assessments of extreme natural hazards based on historic data.

  16. Assessment of three systems to empower the patient and decrease the risk of adverse drug events.

    PubMed

    Lawton, Kitta; Skjoet, Peter

    2011-01-01

    One way to reduce adverse drug events (ADEs) is to empower the patient to participate in the control of medication. This empowerment can be supported in different ways by making knowledge and information available to the patient. This study examines the usefulness and safety of two different systems on the background of a paper-based medication list presenting prescribed medicine presently used in hospitals in Copenhagen. Each of the systems examined aims to reduce ADEs but presents information in different levels of detail, and anticipates different level of prior knowledge from the patient: a Web-based prototype presenting medication, lab-results and alerts, and a cell phone-based prototype presenting alerts. Six patients were introduced to each of the systems by performing small tasks and subsequently interviewed. The patients found the paper-based medication list useful and comprehensive for control of own prescribed medication. The Web-based prototype also proved to be useful, but drug and lab values were hard to correlate, and the alerts were hard to understand. The cell phone-based prototype proved less useful as the patients were challenged to vision the applicability of the system. Furthermore, it is a safety issue that the information the alert is based upon, stems from the patient alone. We conclude that, in order for the Web-based system as well as the cell phone system to empower patient and increase patient safety, further development of the systems is necessary. PMID:21685630

  17. A general causal model to guide alcohol, tobacco, and illicit drug prevention: assessing the research evidence.

    PubMed

    Birckmayer, Johanna D; Holder, Harold D; Yacoubian, George S; Friend, Karen B

    2004-01-01

    The problems associated with the use of alcohol, tobacco, and other drugs (ATOD) extract a significant health, social, and economic toll on American society. While the field of substance abuse prevention has made great strides during the past decade, two major challenges remain. First, the field has been disorganized and fragmented with respect to its research and prevention practices; that is, there are often separate ATOD prevention "specialists." Second, both the prevention researchers who test the efficacy of specific prevention strategies and the practitioners who implement prevention efforts often lack an overall perspective to guide strategy selection. To address these limitations, we present an ATOD causal model that seeks to identify those variables (Domains) that are theoretically salient and empirically connected across alcohol, tobacco, and illicit drugs. For the researcher, the model demonstrates important commonalities, as well as gaps, in the literature. For the practitioner, the model is a means to recognize both the complexity of the community system that produces ATOD problems and the multiple intervention points that are possible within this system. Researchers and practitioners are thus challenged to work synergistically to find effective and cost-effective approaches to change or reduce ATOD use and associated problems. PMID:15638215

  18. Drug pharmacokinetics and pharmacodynamics: Technological considerations

    SciTech Connect

    Fowler, J.S.; Volkow, N.D.; Wolf, A.P.

    1992-12-31

    Additionally, the use of PET to examine drug pharmacokinetics and pharmacadynamics and the relationship of these properties to the behavioral, therapeutic and toxic properties of drugs and substances of abuse is emerging as a powerful new scientific tool. The pharmacokinetic properties of a drug, which comprises all of the biological processes which determine the fraction of the drug available, can be measured using the labeled drug itself. For example, the labeled drug can be used to measure the absolute uptake, regional distribution and kinetics of a drug at its site of action in the body. Additionally the labeled drug and whole body its labeled metabolites and thus provide information an potential toxic effects as well as tissue half lives. On the other hand, different labeled tracers can be used to assess drug pharmacodynamics which include the biological Processes involved in the drug`s effects. For example, with appropriate radiotracers, the effects of a drug on metabolism, neurotransmitter activity, blood flew, enzyme activity or other processes can be probed.

  19. Assessment of size-dependent mercury distribution in King Mackerel, Scomberomorus cavalla

    SciTech Connect

    Voit, E.O.; Balthis, W.L. |

    1994-12-31

    The assessment of health risks from fish contamination and the issuance of advisories require accurate characterizations of the actual contaminant concentrations in fish of every relevant size. Such characterizations should not only contain statistical measures of location and variation, but provide a complete parameterization of the contaminant distribution for each given size class. This paper proposes two methods for determining such distributions from scatter diagrams of contaminant concentration versus fish length and illustrates them with an analysis of mercury contaminant in king mackerel, Scomberomorus cavalla. The first method consists of fitting contamination data with a family of S-distributions. This family shows trends in its defining parameter values, and these trends provide a comprehensive characterization of the measured contaminant concentrations. Each S-distribution has a rather simple mathematical structure from which one readily obtains secondary characteristics like quantiles, which are necessary for advanced simulation purposes. The second method takes into account that contaminant accumulation is the outcome of a metabolic process. When this process is modeled as a system of differential equations, it can be reformulated in such a way that it describes how the contaminant distribution changes over a given period of time. The resulting distributions have a more complicated structure than those obtained with the first method, but they allow them to bridge the gap between individual metabolic accumulation processes and trends in populations.

  20. Non-contact assessment of melanin distribution via multispectral temporal illumination coding

    NASA Astrophysics Data System (ADS)

    Amelard, Robert; Scharfenberger, Christian; Wong, Alexander; Clausi, David A.

    2015-03-01

    Melanin is a pigment that is highly absorptive in the UV and visible electromagnetic spectra. It is responsible for perceived skin tone, and protects against harmful UV effects. Abnormal melanin distribution is often an indicator for melanoma. We propose a novel approach for non-contact melanin distribution via multispectral temporal illumination coding to estimate the two-dimensional melanin distribution based on its absorptive characteristics. In the proposed system, a novel multispectral, cross-polarized, temporally-coded illumination sequence is synchronized with a camera to measure reflectance under both multispectral and ambient illumination. This allows us to eliminate the ambient illumination contribution from the acquired reflectance measurements, and also to determine the melanin distribution in an observed region based on the spectral properties of melanin using the Beer-Lambert law. Using this information, melanin distribution maps can be generated for objective, quantitative assessment of skin type of individuals. We show that the melanin distribution map correctly identifies areas with high melanin densities (e.g., nevi).

  1. The integration of renewable energy sources into electric power distribution systems. Volume 1: National assessment

    SciTech Connect

    Barnes, P.R.; Van Dyke, J.W.; Tesche, F.M.; Zaininger, H.W.

    1994-06-01

    Renewable energy technologies such as photovoltaic, solar thermal electricity, and wind turbine power are environmentally beneficial sources of electric power generation. The integration of renewable energy sources into electric power distribution systems can provide additional economic benefits because of a reduction in the losses associated with transmission and distribution lines. Benefits associated with the deferment of transmission and distribution investment may also be possible for cases where there is a high correlation between peak circuit load and renewable energy electric generation, such as photovoltaic systems in the Southwest. Case studies were conducted with actual power distribution system data for seven electric utilities with the participation of those utilities. Integrating renewable energy systems into electric power distribution systems increased the value of the benefits by about 20 to 55% above central station benefits in the national regional assessment. In the case studies presented in Vol. II, the range was larger: from a few percent to near 80% for a case where costly investments were deferred. In general, additional savings of at least 10 to 20% can be expected by integrating at the distribution level. Wind energy systems were found to be economical in good wind resource regions, whereas photovoltaic systems costs are presently a factor of 2.5 too expensive under the most favorable conditions.

  2. The integration of renewable energy sources into electric power distribution systems. Volume 1: National assessment

    NASA Astrophysics Data System (ADS)

    Barnes, P. R.; Vandyke, J. W.; Tesche, F. M.; Zaininger, H. W.

    1994-06-01

    Renewable energy technologies such as photovoltaic, solar thermal electricity, and wind turbine power are environmentally beneficial sources of electric power generation. The integration of renewable energy sources into electric power distribution systems can provide additional economic benefits because of a reduction in the losses associated with transmission and distribution lines. Benefits associated with the deferment of transmission and distribution investment may also be possible for cases where there is a high correlation between peak circuit load and renewable energy electric generation, such as photovoltaic systems in the Southwest. Case studies were conducted with actual power distribution system data for seven electric utilities with the participation of those utilities. Integrating renewable energy systems into electric power distribution systems increased the value of the benefits by about 20 to 55% above central station benefits in the national regional assessment. In the case studies presented in Vol. 2, the range was larger: from a few percent to near 80% for a case where costly investments were deferred. In general, additional savings of at least 10 to 20% can be expected by integrating at the distribution level. Wind energy systems were found to be economical in good wind resource regions, whereas photovoltaic systems costs are presently a factor of 2.5 too expensive under the most favorable conditions.

  3. A unique drug distribution process for radium Ra 223 dichloride injection and its implication for product quality, patient privacy, and delineation of professional responsibilities.

    PubMed

    Dansereau, Raymond N

    2014-11-01

    On May 15, 2013, Bayer Healthcare Pharmaceuticals announced that it had received marketing approval for the therapeutic radioactive medication radium Ra 223 dichloride injection (Xofigo; Ra 223). The product acquisition and distribution process for hospital-based nuclear pharmacies and nuclear medicine services is unlike any other. The product is distributed as a low-risk compounded sterile preparation through a single compounding nuclear pharmacy located in Denver, Colorado, pursuant to a prescription. This model for drug distribution and delivery to the user institution has implications for product quality, patient privacy, and delineation of professional responsibilities. PMID:25301826

  4. Drug Resistance of Enteric Bacteria XIII. Distribution of R Factors in Escherichia coli Strains Isolated from Livestock

    PubMed Central

    Mitsuhashi, Susumu; Hashimoto, Hajime; Suzuki, Kaname

    1967-01-01

    Escherichia coli strains isolated from 151 swine and 108 fowl, which were kept at the Animal Health Center, Maebashi, Japan, were surveyed for drug resistance and distribution of R factors. All of the swine and 38% of the fowl excreted E. coli strains resistant to tetracycline, chloramphenicol, streptomycin, and sulfanilamide, or certain combinations thereof. Among 278 resistant cultures isolated from swine, 13% were found to be resistant to one antibiotic, whereas 87% were resistant to more than one antibiotic. Among these resistant strains, 40% carried R factors which were transferable by the usual conjugal process. The resistance patterns of these R factors included 36% which were singly resistant and 64% which were multiply resistant. Among 54 resistant cultures isolated from fowl, 24% were singly resistant and 76% were multiply resistant. Of the resistant strains from fowl, 22% carried R factors. The resistance patterns of R factors included 50% of the singly resistant type and 50% which were multiply resistant. In spite of feeding with dairy products containing only tetracycline, a high incidence of multiple resistance was observed in the E. coli strains and the R factors isolated from these animals. PMID:4860911

  5. Independent Orbiter Assessment (IOA): Analysis of the Electrical Power Distribution and Control Subsystem, Volume 2

    NASA Technical Reports Server (NTRS)

    Schmeckpeper, K. R.

    1987-01-01

    The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. This report documents the independent analysis results corresponding to the Orbiter Electrical Power Distribution and Control (EPD and C) hardware. The EPD and C hardware performs the functions of distributing, sensing, and controlling 28 volt DC power and of inverting, distributing, sensing, and controlling 117 volt 400 Hz AC power to all Orbiter subsystems from the three fuel cells in the Electrical Power Generation (EPG) subsystem. Volume 2 continues the presentation of IOA analysis worksheets and contains the potential critical items list.

  6. Risk assessment of premature drug release during wet granulation of ordered mesoporous silica loaded with poorly soluble compounds itraconazole, fenofibrate, naproxen, and ibuprofen.

    PubMed

    Vialpando, Monica; Backhuijs, Floris; Martens, Johan A; Van den Mooter, Guy

    2012-05-01

    In this study, the potential of wet granulation of ordered mesoporous silica (OMS) material was evaluated to assess the risk of premature drug release during processing and to improve the bulk powder flow properties and compactibility for the development of an immediate release oral dosage form. The poorly water soluble model compounds, itraconazole, fenofibrate, naproxen, and ibuprofen were loaded into the model OMS, COK-12, and granulated using a polyvinylpyrrolidone (PVP) binder solution. Preliminary assessments were made with itraconazole loaded COK-12 to study the effects of the initial drug load, binder concentration, binder addition rate, and granulation temperature on premature drug release. Comparison to pure COK-12 revealed particle size enlargement and enhanced powder flow based on Carr Index and Hausner Ratio results. Following compression to 120 MPa, the compactibility of the granulated material also improved when compared to the untreated COK-12. In vitro release of itraconazole from the compressed granulated material was assessed with and without the disintegrant, croscarmellose sodium. Incorporation of 2.4 wt. croscarmellose sodium prior to compression successfully recovered the slight release loss following compression. To assess premature drug release, developments made with itraconazole loaded COK-12 were applied to loaded fenofibrate, naproxen, and ibuprofen. Results from modulated differential scanning calorimetry (MDSC) indicated that the risk of premature drug release during wet granulation was primarily compound dependent. These findings highlight challenges in preparation for a successful manufacturing process of OMS based formulations. PMID:22306694

  7. Assessment of dye distribution in sensitized solar cells by microprobe techniques

    NASA Astrophysics Data System (ADS)

    Barreiros, M. A.; Corregidor, V.; Alves, L. C.; Guimarães, F.; Mascarenhas, J.; Torres, E.; Brites, M. J.

    2015-04-01

    Dye sensitized solar cells (DSCs) have received considerable attention once this technology offers economic and environmental advantages over conventional photovoltaic (PV) devices. The PV performance of a DSC relies on the characteristics of its photoanode, which typically consists of a nanocrystalline porous TiO2 film, enabled with a large adsorptive surface area. Dye molecules that capture photons from light during device operation are attached to the film nanoparticles. The effective loading of the dye in the TiO2 electrode is of paramount relevance for controlling and optimizing solar cell parameters. Relatively few methods are known today for quantitative evaluation of the total dye adsorbed on the film. In this context, microprobe techniques come out as suitable tools to evaluate the dye surface distribution and depth profile in sensitized films. Electron Probe Microanalysis (EPMA) and Ion Beam Analytical (IBA) techniques using a micro-ion beam were used to quantify and to study the distribution of the Ru organometallic dye in TiO2 films, making use of the different penetration depth and beam sizes of each technique. Different 1D nanostructured TiO2 films were prepared, morphologically characterized by SEM, sensitized and analyzed by the referred techniques. Dye load evaluation in different TiO2 films by three different techniques (PIXE, RBS and EPMA/WDS) provided similar results of Ru/Ti mass fraction ratio. Moreover, it was possible to assess dye surface distribution and its depth profile, by means of Ru signal, and to visualize the dye distribution in sample cross-section through X-ray mapping by EPMA/EDS. PIXE maps of Ru and Ti indicated an homogeneous surface distribution. The assessment of Ru depth profile by RBS showed that some films have homogeneous Ru depth distribution while others present different Ru concentration in the top layer (2 ?m thickness). These results are consistent with the EPMA/EDS maps obtained.

  8. Blinded validation of the isolated arterially perfused rabbit ventricular wedge in preclinical assessment of drug-induced proarrhythmias

    PubMed Central

    Liu, Tengxian; Brown, Barry S; Wu, Ying; Antzelevitch, Charles; Kowey, Peter R; Yan, Gan-Xin

    2007-01-01

    BACKGROUND The development of preclinical models with high predictive value for the identification of drugs with a proclivity to induce Torsade de Pointes (TdP) in the clinic has long been a pressing goal of academia, industry and regulatory agencies alike. The present study provides a blinded appraisal of drugs, in an isolated arterially-perfused rabbit ventricular wedge preparation, with and without the potential to produce TdP. METHODS AND RESULTS Thirteen compounds were tested for their potential for TdP using the rabbit left ventricular wedges. All investigators were blinded to the names, concentrations and molecular weights of the drugs. The compounds were prepared by the study sponsor and sent to the investigator as 4 sets of 13 stock solutions with the order within each set being assigned by a random number generator. Each compound was scored semi-quantitatively for its relative potential for TdP based on its effect on ventricular repolarization measured as QT interval, dispersion of repolarization measured as Tp-e/QT ratio and early afterdepolarizations. Disclosure of the names and concentrations after completion of the study revealed that all compounds known to be free of TdP risk received a score of less or equal to 0.25, whereas those with known TdP risk received a score ranging from 1.00 to 7.25 at concentrations less than 100X their free therapeutic plasma Cmax. CONCLUSIONS Our study provides a blinded evaluation of the isolated arterially-perfused rabbit wedge preparation demonstrating both a high sensitivity and specificity in the assessment of 13 agents with varying propensity for causing TdP. PMID:16876745

  9. Information on new drugs at market entry: retrospective analysis of health technology assessment reports versus regulatory reports, journal publications, and registry reports

    PubMed Central

    Köhler, Michael; Haag, Susanne; Biester, Katharina; Brockhaus, Anne Catharina; McGauran, Natalie; Grouven, Ulrich; Kölsch, Heike; Seay, Ulrike; Hörn, Helmut; Moritz, Gregor; Staeck, Kerstin

    2015-01-01

    Background When a new drug becomes available, patients and doctors require information on its benefits and harms. In 2011, Germany introduced the early benefit assessment of new drugs through the act on the reform of the market for medicinal products (AMNOG). At market entry, the pharmaceutical company responsible must submit a standardised dossier containing all available evidence of the drug’s added benefit over an appropriate comparator treatment. The added benefit is mainly determined using patient relevant outcomes. The “dossier assessment” is generally performed by the Institute for Quality and Efficiency in Health Care (IQWiG) and then published online. It contains all relevant study information, including data from unpublished clinical study reports contained in the dossiers. The dossier assessment refers to the patient population for which the new drug is approved according to the summary of product characteristics. This patient population may comprise either the total populations investigated in the studies submitted to regulatory authorities in the drug approval process, or the specific subpopulations defined in the summary of product characteristics (“approved subpopulations”). Objective To determine the information gain from AMNOG documents compared with non-AMNOG documents for methods and results of studies available at market entry of new drugs. AMNOG documents comprise dossier assessments done by IQWiG and publicly available modules of company dossiers; non-AMNOG documents comprise conventional, publicly available sources—that is, European public assessment reports, journal publications, and registry reports. The analysis focused on the approved patient populations. Design Retrospective analysis. Data sources All dossier assessments conducted by IQWiG between 1 January 2011 and 28 February 2013 in which the dossiers contained suitable studies allowing for a full early benefit assessment. We also considered all European public assessment reports, journal publications, and registry reports referring to these studies and included in the dossiers. Data analysis We assessed reporting quality for each study and each available document for eight methods and 11 results items (three baseline characteristics and eight patient relevant outcomes), and dichotomised them as “completely reported” or “incompletely reported (including items not reported at all).” For each document type we calculated the proportion of items with complete reporting for methods and results, for each item and overall, and compared the findings. Results 15 out of 27 dossiers were eligible for inclusion and contained 22 studies. The 15 dossier assessments contained 28 individual assessments of 15 total study populations and 13 approved subpopulations. European public assessment reports were available for all drugs. Journal publications were available for 14 out of 15 drugs and 21 out of 22 studies. A registry report in ClinicalTrials.gov was available for all drugs and studies; however, only 11 contained results. In the analysis of total study populations, the AMNOG documents reached the highest grade of completeness, with about 90% of methods and results items completely reported. In non-AMNOG documents, the rate was 75% for methods and 52% for results items; journal publications achieved the best rates, followed by European public assessment reports and registry reports. The analysis of approved subpopulations showed poorer complete reporting of results items, particularly in non-AMNOG documents (non-AMNOG versus AMNOG: 11% v 71% for overall results items and 5% v 70% for patient relevant outcomes). The main limitation of our analysis is the small sample size. Conclusion Conventional, publicly available sources provide insufficient information on new drugs, especially on patient relevant outcomes in approved subpopulations. This type of information is largely available in AMNOG documents, albeit only partly in English. The AMNOG approach could be used internationally to dev

  10. Religiosity and HIV-related drug risk behavior: a multidimensional assessment of individuals from communities with high rates of drug use

    PubMed Central

    Billioux, Veena G.; Sherman, Susan G.; Latkin, Carl A.

    2012-01-01

    We examined the relationship between religiosity and HIV-related drug risk behavior among individuals from communities with high rates of drug use who participated in the SHIELD (Self-Help in Eliminating Life Threatening Disease) study. This analysis examined the dimensions of religious ideation, religious participation and religious support separately to further understand the relationship with risk taking. Results indicate that greater religious participation appeared to be the dimension most closely associated with drug behaviors. Specifically, we found that those with greater religious participation are significantly less likely to report recent opiates or cocaine use; injection drug use; crack use; needle, cotton or cooker sharing. Future work to understand the nature of these associations will assist in the development of interventions in communities with high rates of drug use. PMID:22399161

  11. Trafficking of drug candidates relevant for sports drug testing: detection of non-approved therapeutics categorized as anabolic and gene doping agents in products distributed via the Internet.

    PubMed

    Thevis, Mario; Geyer, Hans; Thomas, Andreas; Schänzer, Wilhelm

    2011-05-01

    Identifying the use of non-approved drugs by cheating athletes has been a great challenge for doping control laboratories. This is due to the additional complexities associated with identifying relatively unknown and uncharacterized compounds and their metabolites as opposed to known and well-studied therapeutics. In 2010, the prohibited drug candidates and gene doping substances AICAR and GW1516, together with the selective androgen receptor modulator (SARM) MK-2866 were obtained by the Cologne Doping Control Laboratory from Internet suppliers and their structure, quantity, and formulation elucidated. All three compounds proved authentic as determined by liquid chromatography-high resolution/high accuracy (tandem) mass spectrometry and comparison to reference material. While AICAR was provided as a colourless powder in 100 mg aliquots, GW1516 was obtained as an orange/yellow suspension in water/glycerol (150 mg/ml), and MK-2866 (25 mg/ml) was shipped dissolved in polyethylene glycol (PEG) 300. In all cases, the quantified amounts were considerably lower than indicated on the label. The substances were delivered via courier, with packaging identifying them as containing 'amino acids' and 'green tea extract', arguably to circumvent customs control. Although all of the substances were declared 'for research only', their potential misuse in illicit performance-enhancement cannot be excluded; moreover sports drug testing authorities should be aware of the facile availability of black market copies of these drug candidates. PMID:21538997

  12. Optimal Capacity and Location Assessment of Natural Gas Fired Distributed Generation in Residential Areas

    NASA Astrophysics Data System (ADS)

    Khalil, Sarah My

    With ever increasing use of natural gas to generate electricity, installed natural gas fired microturbines are found in residential areas to generate electricity locally. This research work discusses a generalized methodology for assessing optimal capacity and locations for installing natural gas fired microturbines in a distribution residential network. The overall objective is to place microturbines to minimize the system power loss occurring in the electrical distribution network; in such a way that the electric feeder does not need any up-gradation. The IEEE 123 Node Test Feeder is selected as the test bed for validating the developed methodology. Three-phase unbalanced electric power flow is run in OpenDSS through COM server, and the gas distribution network is analyzed using GASWorkS. The continual sensitivity analysis methodology is developed to select multiple DG locations and annual simulation is run to minimize annual average losses. The proposed placement of microturbines must be feasible in the gas distribution network and should not result into gas pipeline reinforcement. The corresponding gas distribution network is developed in GASWorkS software, and nodal pressures of the gas system are checked for various cases to investigate if the existing gas distribution network can accommodate the penetration of selected microturbines. The results indicate the optimal locations suitable to place microturbines and capacity that can be accommodated by the system, based on the consideration of overall minimum annual average losses as well as the guarantee of nodal pressure provided by the gas distribution network. The proposed method is generalized and can be used for any IEEE test feeder or an actual residential distribution network.

  13. Comparative risk assessment of alcohol, tobacco, cannabis and other illicit drugs using the margin of exposure approach

    PubMed Central

    Lachenmeier, Dirk W.; Rehm, Jürgen

    2015-01-01

    A comparative risk assessment of drugs including alcohol and tobacco using the margin of exposure (MOE) approach was conducted. The MOE is defined as ratio between toxicological threshold (benchmark dose) and estimated human intake. Median lethal dose values from animal experiments were used to derive the benchmark dose. The human intake was calculated for individual scenarios and population-based scenarios. The MOE was calculated using probabilistic Monte Carlo simulations. The benchmark dose values ranged from 2?mg/kg bodyweight for heroin to 531?mg/kg bodyweight for alcohol (ethanol). For individual exposure the four substances alcohol, nicotine, cocaine and heroin fall into the “high risk” category with MOE < 10, the rest of the compounds except THC fall into the “risk” category with MOE < 100. On a population scale, only alcohol would fall into the “high risk” category, and cigarette smoking would fall into the “risk” category, while all other agents (opiates, cocaine, amphetamine-type stimulants, ecstasy, and benzodiazepines) had MOEs > 100, and cannabis had a MOE > 10,000. The toxicological MOE approach validates epidemiological and social science-based drug ranking approaches especially in regard to the positions of alcohol and tobacco (high risk) and cannabis (low risk). PMID:25634572

  14. Substandard antimalarials available in Afghanistan: a case for assessing the quality of drugs in resource poor settings.

    PubMed

    Lalani, Mirza; Kaur, Harparkash; Mohammed, Nader; Mailk, Naiela; van Wyk, Albert; Jan, Sakhi; Kakar, Rishtya Meena; Mojadidi, Mohammed Khalid; Leslie, Toby

    2015-06-01

    Good-quality antimalarials are crucial for the effective treatment and control of malaria. A total of 7,740 individual and packaged tablets, ampoules, and syrups were obtained from 60 randomly selected public (N = 35) and private outlets (N = 25) in Afghanistan. Of these, 134 samples were screened using the Global Pharma Health Fund (GPHF) MiniLab® in Kabul with 33/126 (26%) samples failing the MiniLab® disintegration test. The quality of a subsample (N = 37) of cholorquine, quinine, and sulfadoxine/pyrimethamine tablets was assessed by in vitro dissolution testing following U.S. Pharmacopeia (USP) monographs at a bioanalytical laboratory in London, United Kingdom. Overall, 12/32 (32%) samples of sulfadoxine/pyrimethamine and quinine were found not to comply with the USP tolerance limits. Substandard antimalarials were available in Afghanistan demonstrating that continuous monitoring of drug quality is warranted. However, in Afghanistan as in many low-income countries, capacity to determine and monitor drug quality using methods such as dissolution testing needs to be established to empower national authorities to take appropriate action in setting up legislation and regulation. PMID:25897070

  15. Human CD34(+) progenitor hematopoiesis in liquid culture for in vitro assessment of drug-induced myelotoxicity.

    PubMed

    Guo, Liang; Hamre, John; Davis, Myrtle; Parchment, Ralph E

    2016-03-01

    Utilization of validated CFU-GM assays for myelotoxicity screening is hampered by its labor-intensive and low-throughput nature. Herein, we transformed the defined CFU-GM assay conditions and IC90 endpoint into a higher throughput format. Human CD34(+) hematopoietic progenitors were cultured in a 96-well plate for 14days with the same cytokine (rhGM-CSF) used in the CFU-GM assay. Expansion and differentiation toward myeloid lineages were manifested by characteristic changes in nuclear and cytoplasmic morphology and by temporal expression patterns of CD34, CD11b and CD13 markers. Inhibition of CD34(+) cell myelopoiesis by 12 anticancer drugs known to induce myelotoxicity in the clinic was quantifiable using either general cytotoxicity endpoints (cell growth area or total nucleus count) or lineage specific readouts (count of cells expressing CD11b and/or CD13). The IC50 and IC90 values derived from the concentration-response curves of 14-day drug exposure in CD34(+) cell culture were highly correlated with those from the international validation study of the CFU-GM assay, demonstrating capability to assess general cytotoxicity, cell proliferation and myelopoiesis simultaneously. These results suggest that this human CD34(+) hematopoietic progenitor cell assay can be used as a direct replacement for the validated, low throughput CFU-GM assay, and could expand application of in vitro myelotoxicity testing. PMID:26616282

  16. Substandard Antimalarials Available in Afghanistan: A Case for Assessing the Quality of Drugs in Resource Poor Settings

    PubMed Central

    Lalani, Mirza; Kaur, Harparkash; Mohammed, Nader; Mailk, Naiela; van Wyk, Albert; Jan, Sakhi; Kakar, Rishtya Meena; Mojadidi, Mohammed Khalid; Leslie, Toby

    2015-01-01

    Good-quality antimalarials are crucial for the effective treatment and control of malaria. A total of 7,740 individual and packaged tablets, ampoules, and syrups were obtained from 60 randomly selected public (N = 35) and private outlets (N = 25) in Afghanistan. Of these, 134 samples were screened using the Global Pharma Health Fund (GPHF) MiniLab® in Kabul with 33/126 (26%) samples failing the MiniLab® disintegration test. The quality of a subsample (N = 37) of cholorquine, quinine, and sulfadoxine/pyrimethamine tablets was assessed by in vitro dissolution testing following U.S. Pharmacopeia (USP) monographs at a bioanalytical laboratory in London, United Kingdom. Overall, 12/32 (32%) samples of sulfadoxine/pyrimethamine and quinine were found not to comply with the USP tolerance limits. Substandard antimalarials were available in Afghanistan demonstrating that continuous monitoring of drug quality is warranted. However, in Afghanistan as in many low-income countries, capacity to determine and monitor drug quality using methods such as dissolution testing needs to be established to empower national authorities to take appropriate action in setting up legislation and regulation. PMID:25897070

  17. Analysis of drugs of abuse by online SPE-LC high resolution mass spectrometry: communal assessment of consumption.

    PubMed

    Heuett, Nubia V; Ramirez, Cesar E; Fernandez, Adolfo; Gardinali, Piero R

    2015-04-01

    An online SPE-LC-HRMS method was developed to monitor the consumption of 18 drugs of abuse (DOAs) including amphetamines, opioids, cocainics, cannabinoids, lysergics, and their corresponding metabolites in a well characterized college campus setting via wastewater analysis. Filtered and diluted (10×) sewage water samples (5 mL inj.) were automatically pre-concentrated and analyzed in 15 min using a Thermo EQuan MAX online SPE system equipped with a HyperSep™ Retain PEP (20×2.1 mm×12 ?m) SPE column and a Hypersil Gold™ aQ (150×2.1 mm×3 ?m) analytical column. A Q Exactive™ Hybrid Quadrupole-Orbitrap HRMS was used in full scan mode (R=140,000) for positive identification, and quantitation of target compounds. Method detection limits for all analytes ranged between 0.6 and 1.7 ng/L in sewage. A total of 14 DOAs were detected from two different locations (dorms and main college campus) within a one-year period. Most frequently detected drugs throughout the entire study were amphetamine (>96%) and THC's metabolite 11-nor-9-carboxy-?-9-THC (>100%) with maximum concentrations of 5956 and 2413 ng/L respectively. Daily doses per 1000 people were determined in order to assess consumption of THC, amphetamine, heroin and cocaine, in both dorms and main campus. PMID:25553546

  18. Post-Mass Drug Administration Transmission Assessment Survey for Elimination of Lymphatic Filariasis in La Ciénaga, Dominican Republic.

    PubMed

    Noland, Gregory S; Blount, Stephen; Gonzalez, Manuel

    2015-12-01

    The Dominican Republic is one of four remaining countries in the Americas with lymphatic filariasis (LF). Annual mass drug administration (MDA) with albendazole and diethylcarbamazine was conducted in La Ciénaga, an impoverished urban barrio in Santo Domingo, from 2004 to 2006. Eight years after the last MDA, a transmission assessment survey (TAS) was conducted in November-December 2014 to determine if LF transmission remains absent. Of 815 first and second grade primary school students (mean age: 6.51 years; range 5-9) tested by immunochromatographic test (ICT), zero (0.0%) were positive. This is below the TAS critical cutoff of nine, indicating that the area "passed" TAS and that transmission remains interrupted in La Ciénaga. Importantly, this also provides evidence that three rounds of effective (> 65% coverage) MDA, likely aided by environmental improvements and periodic school-based albendazole monotherapy MDA, achieved interruption of LF transmission from a relatively low-transmission setting. PMID:26503279

  19. Utah Drug Use Questionnaire.

    ERIC Educational Resources Information Center

    Governor's Citizen Advisory Committee on Drugs, Salt Lake City, UT.

    This questionnaire assesses drug use practices in junior and senior high school students. The 21 multiple choice items pertain to drug use practices, use history, available of drugs, main reason for drug use, and demographic data. The questionnaire is untimed, group administered, and may be given by the classroom teacher in about 10 minutes. Item…

  20. A novel QSAR model of Salmonella mutagenicity and its application in the safety assessment of drug impurities

    SciTech Connect

    Valencia, Antoni; Prous, Josep; Mora, Oscar; Sadrieh, Nakissa; Valerio, Luis G.

    2013-12-15

    As indicated in ICH M7 draft guidance, in silico predictive tools including statistically-based QSARs and expert analysis may be used as a computational assessment for bacterial mutagenicity for the qualification of impurities in pharmaceuticals. To address this need, we developed and validated a QSAR model to predict Salmonella t. mutagenicity (Ames assay outcome) of pharmaceutical impurities using Prous Institute's Symmetry?, a new in silico solution for drug discovery and toxicity screening, and the Mold2 molecular descriptor package (FDA/NCTR). Data was sourced from public benchmark databases with known Ames assay mutagenicity outcomes for 7300 chemicals (57% mutagens). Of these data, 90% was used to train the model and the remaining 10% was set aside as a holdout set for validation. The model's applicability to drug impurities was tested using a FDA/CDER database of 951 structures, of which 94% were found within the model's applicability domain. The predictive performance of the model is acceptable for supporting regulatory decision-making with 84 ± 1% sensitivity, 81 ± 1% specificity, 83 ± 1% concordance and 79 ± 1% negative predictivity based on internal cross-validation, while the holdout dataset yielded 83% sensitivity, 77% specificity, 80% concordance and 78% negative predictivity. Given the importance of having confidence in negative predictions, an additional external validation of the model was also carried out, using marketed drugs known to be Ames-negative, and obtained 98% coverage and 81% specificity. Additionally, Ames mutagenicity data from FDA/CFSAN was used to create another data set of 1535 chemicals for external validation of the model, yielding 98% coverage, 73% sensitivity, 86% specificity, 81% concordance and 84% negative predictivity. - Highlights: • A new in silico QSAR model to predict Ames mutagenicity is described. • The model is extensively validated with chemicals from the FDA and the public domain. • Validation tests show desirable high sensitivity and high negative predictivity. • The model predicted 14 reportedly difficult to predict drug impurities with accuracy. • The model is suitable to support risk evaluation of potentially mutagenic compounds.

  1. Assessing protein conformational sampling methods based on bivariate lag-distributions of backbone angles

    PubMed Central

    Maadooliat, Mehdi; Huang, Jianhua Z.

    2013-01-01

    Despite considerable progress in the past decades, protein structure prediction remains one of the major unsolved problems in computational biology. Angular-sampling-based methods have been extensively studied recently due to their ability to capture the continuous conformational space of protein structures. The literature has focused on using a variety of parametric models of the sequential dependencies between angle pairs along the protein chains. In this article, we present a thorough review of angular-sampling-based methods by assessing three main questions: What is the best distribution type to model the protein angles? What is a reasonable number of components in a mixture model that should be considered to accurately parameterize the joint distribution of the angles? and What is the order of the local sequence–structure dependency that should be considered by a prediction method? We assess the model fits for different methods using bivariate lag-distributions of the dihedral/planar angles. Moreover, the main information across the lags can be extracted using a technique called Lag singular value decomposition (LagSVD), which considers the joint distribution of the dihedral/planar angles over different lags using a nonparametric approach and monitors the behavior of the lag-distribution of the angles using singular value decomposition. As a result, we developed graphical tools and numerical measurements to compare and evaluate the performance of different model fits. Furthermore, we developed a web-tool (http://www.stat.tamu.edu/?madoliat/LagSVD) that can be used to produce informative animations. PMID:22926831

  2. Photochemical fate and eco-genotoxicity assessment of the drug etodolac.

    PubMed

    Passananti, Monica; Lavorgna, Margherita; Iesce, Maria Rosaria; DellaGreca, Marina; Brigante, Marcello; Criscuolo, Emma; Cermola, Flavio; Isidori, Marina

    2015-06-15

    The photochemical behavior of etodolac was investigated under various irradiation conditions. Kinetic data were obtained after irradiation of 10(-4) M aqueous solutions by UVB, UVA and direct exposure to sunlight. The Xenon lamp irradiation was used in order to determine the photodegradation quantum yield under sun-simulated condition (?sun). The value was determined to be=0.10±0.01. In order to obtain photoproducts and for mechanistic purposes, experiments were carried out on more concentrated solutions by exposure to sunlight and to UVA and UVB lamps. The drug underwent photooxidative processes following an initial oxygen addition to the double bond of the five membered ring and was mainly converted into a spiro compound and a macrolactam. Ecotoxicity tests were performed on etodolac, its photostable spiro derivative and its sunlight irradiation mixture on two different aquatic trophic levels, plants (algae) and invertebrates (rotifers and crustaceans). Mutagenesis and genotoxicity were detected on bacterial strains. The results showed that only etodolac had long term effects on rotifers although at concentrations far from environmental detection values. A mutagenic and genotoxic potential was found for its derivative. PMID:25765378

  3. Mitochondrial Profiling of Acute Myeloid Leukemia in the Assessment of Response to Apoptosis Modulating Drugs

    PubMed Central

    Ishizawa, Jo; Kojima, Kensuke; McQueen, Teresa; Ruvolo, Vivian; Chachad, Dhruv; Nogueras-Gonzalez, Graciela M.; Huang, Xuelin; Pierceall, William E.; Dettman, E. J.; Cardone, Michael H.; Shacham, Sharon; Konopleva, Marina; Andreeff, Michael

    2015-01-01

    BH3 profiling measures the propensity of transformed cells to undergo intrinsic apoptosis and is determined by exposing cells to BH3-mimicking peptides. We hypothesized that basal levels of prosurvival BCL-2 family proteins may modulate the predictive power of BH3 profiling and termed it mitochondrial profiling. We investigated the correlation between cell sensitivity to apoptogenic agents and mitochondrial profiling, using a panel of acute myeloid leukemias induced to undergo apoptosis by exposure to cytarabine, the BH3 mimetic ABT-199, the MDM2 inhibitor Nutlin-3a, or the CRM1 inhibitor KPT-330. We found that the apoptogenic efficacies of ABT-199 and cytarabine correlated well with BH3 profiling reflecting BCL2, but not BCL-XL or MCL-1 dependence. Baseline BCL-2 protein expression analysis increased the ability of BH3 profiling to predict resistance mediated by MCL-1. By utilizing engineered cells with overexpression or knockdown of BCL-2 family proteins, Ara-C was found to be independent, while ABT-199 was dependent on BCL-XL. BCL-2 and BCL-XL overexpression mediated resistance to KPT-330 which was not reflected in the BH3 profiling assay, or in baseline BCL-2 protein levels. In conclusion, mitochondrial profiling, the combination of BH3 profiling and prosurvival BCL-2 family protein analysis, represents an improved approach to predict efficacy of diverse agents in AML and may have utility in the design of more effective drug combinations. PMID:26375587

  4. Distribution and quantitative assessment of world crude oil reserves and resources

    USGS Publications Warehouse

    Masters, Charles D.; Root, David H.; Dietzman, William D.

    1983-01-01

    World Demonstrated Reserves of crude oil are approximately 723 billion barrels of oil (BBO). Cumulative production is 445 BBO and annual production is 20 BBO. Demonstrated Reserves of crude-oil have declined over the past 10 years consistent with discoveries lagging production over the same period. The assessment of Undiscovered Resources shows a 90 percent probability that the amount discoverable lies between 321 and 1,417 BBO, 550 BBO being the most likely value. The most likely value for Ultimate recoverable resources is 1,718 BBO. The distribution of Ultimate Resources of crude oil will remain highly skewed toward the Middle East; no frontier areas that have potentials large enough to significantly affect present distribution are recognized. Rates of discovery have continued to decline over the past 20 years even though exploration activity has increased in recent years. Prudence dictates, therefore, that the low side of the assessment of Undiscovered Resources be responsibly considered and that alternate energy sources be a part of future planning. Extra-heavy oil and bitumen are assessed separately, with Reserves being figured as the annual productive capacity of installed facilities times 25 years. The annual production of extra-heavy oil is about 8 million barrels and of bitumen about 60 million barrels.

  5. Drug pharmacokinetics and pharmacodynamics: Technological considerations

    SciTech Connect

    Fowler, J.S.; Volkow, N.D.; Wolf, A.P.

    1992-01-01

    Additionally, the use of PET to examine drug pharmacokinetics and pharmacadynamics and the relationship of these properties to the behavioral, therapeutic and toxic properties of drugs and substances of abuse is emerging as a powerful new scientific tool. The pharmacokinetic properties of a drug, which comprises all of the biological processes which determine the fraction of the drug available, can be measured using the labeled drug itself. For example, the labeled drug can be used to measure the absolute uptake, regional distribution and kinetics of a drug at its site of action in the body. Additionally the labeled drug and whole body its labeled metabolites and thus provide information an potential toxic effects as well as tissue half lives. On the other hand, different labeled tracers can be used to assess drug pharmacodynamics which include the biological Processes involved in the drug's effects. For example, with appropriate radiotracers, the effects of a drug on metabolism, neurotransmitter activity, blood flew, enzyme activity or other processes can be probed.

  6. Screening of drugs and their assessment for use against the strobilate stage of Echinococcus

    PubMed Central

    Gemmell, M. A.

    1968-01-01

    From time to time, reports of anthelmintic trials are published indicating that a compound is, or is not, effective against Echinococcus granulosus in dogs. In some of these reports, an attempt is made to assess the efficacy of the compound from inadequate data. This paper reviews the problems associated with selecting, screening and defining the therapeutic dose-rate of a compound against E. granulosus. From this evaluation, a programme is defined, which, if followed, should result in the selection of promising compounds and the rejection of unsuccessful compounds at specific stages during the programme. PMID:5303840

  7. Antineoplastic Drugs

    NASA Astrophysics Data System (ADS)

    Sadée, Wolfgang; El Sayed, Yousry Mahmoud

    The limited scope of therapeutic drug-level monitoring in cancer chemotherapy results from the often complex biochemical mechanisms that contribute to antineoplastic activity and obscure the relationships among drug serum levels and therapeutic benefits. Moreover, new agents for cancer chemotherapy are being introduced at a more rapid rate than for the treatment of other diseases, although the successful application of therapeutic drug-level monitoring may require several years of intensive study of the significance of serum drug levels. However, drug level monitoring can be of considerable value during phase I clinical trials of new antineoplastic agents in order to assess drug metabolism, bioavailability, and intersubject variability; these are important parameters in the interpretation of clinical studies, but have no immediate benefit to the patient. High performance liquid chromatography (HPLC) probably represents the most versatile and easily adaptable analytical technique for drug metabolite screening (1). HPLC may therefore now be the method of choice during phase I clinical trials of antineoplastic drugs. For example, within a single week we developed an HPLC assay—using a C18 reverse-phase column, UV detection, and direct serum injection after protein precipitation—for the new radiosensitizer, misonidazole (2).

  8. Assessment of re-aggregated human pancreatic islets for secondary drug screening

    PubMed Central

    Ramachandran, K; Peng, X; Bokvist, K; Stehno-Bittel, L

    2014-01-01

    BACKGROUND AND PURPOSE Insulin secretion from isolated pancreatic islets is a pivotal assay in developing novel insulin secretagogues, given its good correlation with in vivo efficacy. Because the supply of human islets is limited, this assay is typically run with rodent islets, which do not address species differences and are low-throughput, because of the size matching or volume normalization required. Here we have evaluated the suitability of human re-aggregated islets for this assay. EXPERIMENTAL APPROACH We generated re-aggregated human islets of a consistent size, using micromolds and compared their responses with those of native human and rat islets, to known secretagogues and inhibitors of insulin release. KEY RESULTS Insulin secretion from rat islets, human islets and human re-aggregated cell clusters was concentration-dependently increased by glucose. The calcium channel agonist, Bay K 8644, stimulated insulin secretion in native rat islets and human re-aggregated islets, but not native human islets. Glibenclamide and tolbutamide were more effective and potent in re-aggregated human clusters compared with the other two preparations. Rat islets outperformed both human preparations of islets in response to caffeine, carbachol and glucagon-like peptide-1. Re-aggregated human islet clusters were more sensitive to somatostatin, diazoxide and sodium azide, but rodent islets were more sensitive to nifedipine. CONCLUSIONS AND IMPLICATIONS Human re-aggregated clusters of islet cells, of a constant size were more responsive to all compounds tested than native human islets. Importantly, the assay variability was less in the re-aggregated cluster preparations, which suggests that such re-aggregated cells could be useful for drug development. PMID:24641508

  9. Drug-protein interactions assessed by fluorescence measurements in the real complexes and in model dyads

    NASA Astrophysics Data System (ADS)

    Vayá, Ignacio; Pérez-Ruiz, Raúl; Lhiaubet-Vallet, Virginie; Jiménez, M. Consuelo; Miranda, Miguel A.

    2010-02-01

    In the present work, a systematic fluorescence study on supramolecular systems using two serum albumins (HSA or BSA) as hosts and the nonsteroidal antiinflammatory drugs carprofen (CPF) or naproxen (NPX) as guests has been undertaken. In parallel, model dyads containing Tyr or Trp covalently linked to CPF or NPX have also been investigated. In HSA/(S)-CPF and BSA/(S)-CPF ( ?exc = 266 nm), at 1:1 M ratio, an important degree (more than 40%) of singlet-singlet energy transfer (SSET) was observed to take place. The distance ( r) calculated for energy transfer from the SAs to (S)-CPF through a FRET mechanism was found to be ca. 21 Å. In the case of HSA/(S)-NPX and BSA/(S)-NPX, energy transfer occurred to a lower extent (ca. 7%), and r was determined as ca. 24 Å. In order to investigate the possible excited state interactions between bound ligands and the relevant amino acids present in the protein binding sites, four pairs of model dyads were designed and synthesised, namely ( S, S)-TyrCPF, ( S, R)-TyrCPF, ( S, S)-TrpCPF, ( S, R)-TrpCPF, ( S, S)-TyrNPX, ( S, R)-TyrNPX, ( S, S)-TrpNPX and ( S, R)-TrpNPX. A complete SSET was observed from Tyr or Trp to CPF, since no contribution from the amino acids was present in the emission of the dyads. Likewise, a very efficient Tyr or Trp to NPX energy transfer was observed. Remarkably, in ( S, S)-TrpNPX and ( S, R)-TrpNPX a configuration-dependent reduction in the emission intensity was observed, revealing a strong and stereoselective intramolecular quenching. This effect can be attributed to exciplex formation and is dynamic in nature, as the fluorescence lifetimes were much shorter in ( S, R)- and ( S, S)-TrpNPX (1.5 and 3.1 ns, respectively) than in (S)-NPX (11 ns).

  10. A Phylogeographic Study of the Tiger (Panthera tigris): Using Holocene Distribution Models to Assess Late Pleistocene Range Shifts 

    E-print Network

    Cooper, David Matthew

    2013-11-28

    Assessing tiger distributions through the Late Pleistocene can provide insight to the evolutionary histories of currently recognized tiger subspecies. If global tiger ranges have been continuous, and not sufficiently isolated through glacial...

  11. THE ACQUISITION AND APPLICATION OF ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION (ADME) DATA IN AGRICULTURAL CHEMICAL SAFETY ASSESSMENTS

    EPA Science Inventory

    A multi-sector international group of government, academic, and industry scientists has developed a proposal for an improved testing scheme for assessing the safety of crop protection chemicals. Incorporation of pharmacokinetic studies describing the absorption, distribution, me...

  12. Assessment of rainfall and NDVI anomalies in semi-arid regions using distributed lag models

    NASA Astrophysics Data System (ADS)

    Zewdie, Worku; Csaplovics, E.

    2015-05-01

    The semiarid regions of Ethiopia are exposed to anthropogenic and natural calamities. In this study, we assessed the relationship between Tropical Applications of Meteorology using Satellite data (TAMSAT) and MODIS Normalized Difference Vegetation Index (NDVI) data for the period 2000 to 2014 on decadal and annual basis using multivariate distributed lag (DL) models. Decadal growing season (June to September) values for kaftahumera were calculated from MODIS NDVI data. The growing season NDVI values are highly correlated with the precipitations during the whole study period. A lag of up to 30 days observed in most parts of our study region in which the rainfall has effects on vegetation growth after 40 days. The lag-time effects vary with the distribution of land use types and seasons. A lower correlation was observed in the woodland regions where significant deforestation occurred due to expansion of croplands. The loss in vegetation contributed to the low biomass production attributable to extended loss in vegetation cover.

  13. Examining the Relationship between Gender and Drug-Using Behaviors in Adolescents: The Use of Diagnostic Assessments and Biochemical Analyses of Urine Samples.

    ERIC Educational Resources Information Center

    James, William H.; Moore, David D.

    1999-01-01

    Examines the relationship between gender and drug use among adolescents using diagnostic assessments and biochemical analyses of urine samples. Statistical significance was found in the relationship between gender and marijuana use. The study confirms that more research is needed in this area. (Author/MKA)

  14. Use of In Vitro Absorption, Distribution, Metabolism, and Excretion (ADME) Data in Bioaccumulation Assessments for Fish

    SciTech Connect

    Nichols, John W.; Erhardt, Susan; Dyer, Scott; James, Margaret O.; Moore, Margo; Plotzke, Kathleen; Segner, Helmut; Schultz, Irvin R.; Thomas, Karluss; Vasiluk, Luba; Weisbrod, Anne V.

    2007-11-01

    A scientific workshop was held in 2006 to discuss the use of in vitro Absorption, Distribution, Metabolism, and Excretion (ADME) data in chemical bioaccumulation assessments for fish. Computer-based (in silico) modeling tools are widely used to estimate chemical bioaccumulation. These in silico methods have inherent limitations that result in inaccurate estimates for many compounds. Based on a review of the science workshop participants concluded that two factors, absorption and metabolism, represent the greatest sources of uncertainty in current bioaccumulation models. Both factors can be investigated experimentally using in vitro test systems.

  15. Assessment of the integration capability of system architectures from a complex and distributed software systems perspective

    NASA Astrophysics Data System (ADS)

    Leuchter, S.; Reinert, F.; Müller, W.

    2014-06-01

    Procurement and design of system architectures capable of network centric operations demand for an assessment scheme in order to compare different alternative realizations. In this contribution an assessment method for system architectures targeted at the C4ISR domain is presented. The method addresses the integration capability of software systems from a complex and distributed software system perspective focusing communication, interfaces and software. The aim is to evaluate the capability to integrate a system or its functions within a system-of-systems network. This method uses approaches from software architecture quality assessment and applies them on the system architecture level. It features a specific goal tree of several dimensions that are relevant for enterprise integration. These dimensions have to be weighed against each other and totalized using methods from the normative decision theory in order to reflect the intention of the particular enterprise integration effort. The indicators and measurements for many of the considered quality features rely on a model based view on systems, networks, and the enterprise. That means it is applicable to System-of-System specifications based on enterprise architectural frameworks relying on defined meta-models or domain ontologies for defining views and viewpoints. In the defense context we use the NATO Architecture Framework (NAF) to ground respective system models. The proposed assessment method allows evaluating and comparing competing system designs regarding their future integration potential. It is a contribution to the system-of-systems engineering methodology.

  16. Prediction of drug distribution in subcutaneous xenografts of human tumor cell lines and healthy tissues in mouse: application of the tissue composition-based model to antineoplastic drugs.

    PubMed

    Poulin, Patrick; Chen, Yung-Hsiang; Ding, Xiao; Gould, Stephen E; Hop, Cornelis Eca; Messick, Kirsten; Oeh, Jason; Liederer, Bianca M

    2015-04-01

    Advanced tissue composition-based models can predict the tissue-plasma partition coefficient (Kp ) values of drugs under in vivo conditions on the basis of in vitro and physiological input data. These models, however, focus on healthy tissues and do not incorporate data from tumors. The objective of this study was to apply a tissue composition-based model to six marketed antineoplastic drugs (docetaxel, DOC; doxorubicin, DOX; gemcitabine, GEM; methotrexate, MTX; topotecan, TOP; and fluorouracil, 5-FU) to predict their Kp values in three human tumor xenografts (HCT-116, H2122, and PC3) as well as in healthy tissues (brain, muscle, lung, and liver) under steady-state in vivo conditions in female NCR nude mice. The mechanisms considered in the tissue/tumor composition-based model are the binding to lipids and to plasma proteins, but the transporter effect was also investigated. The method consisted of analyzing tissue composition, performing the pharmacokinetics studies in mice, and calculating the corresponding in vivo Kp values. Analyses of tumor composition indicated that the tumor xenografts contained no or low amounts of common transporters by contrast to lipids. The predicted Kp values were within twofold and threefold of the measured values in 77% and 93% of cases, respectively. However, predictions for brain for each drug, for liver for MTX, and for each tumor xenograft for GEM were disparate from the observed values, and, therefore, not well served by the model. Overall, this study is the first step toward the mechanism-based prediction of Kp values of small molecules in healthy and tumor tissues in mouse when no transporter and permeation limitation effect is evident. This approach will be useful in selecting compounds based on their abilities to penetrate human cancer xenografts with a physiologically based pharmacokinetic (PBPK) model, thereby increasing therapeutic index for chemotherapy in oncology study. PMID:25615572

  17. Kinetic assessment of the potassium ferrate(VI) oxidation of antibacterial drug sulfamethoxazole.

    PubMed

    Sharma, Virender K; Mishra, Santosh K; Ray, Ajay K

    2006-01-01

    Sulfamethoxazole (SMX), a worldwide-applied antibacterial drug, was recently found in surface waters and in secondary wastewater effluents, which may result in ecotoxical effects in the environment. Herein, removal of SMX by environmentally-friendly oxidant, potassium ferrate(VI) (K(2)FeO(4)), is sought by studying the kinetics of the reaction between Fe(VI) and SMX as a function of pH (6.93-9.50) and temperature (15-45 degrees C). The rate law for the oxidation of SMX by Fe(VI) is first-order with respect to each reactant. The observed second-order rate constant decreased non-linearly from 1.33+/-0.08 x 10(3) M(-1)s(-1) to 1.33+/-0.10 x 10(0) M(-1)s(-1) with an increase of pH from 7.00 to 9.50. This is related to protonation of Fe(VI) (HFeO(4)(-) <==> H(+) + FeO(4)(2-); pK(a,HFeO(4)) = 7.23) and sulfamethoxazole (SH <==> H(+) + S(-); pK(a,SH)=5.7). The estimated rate constants were k(11)(HFeO(4)(-) + SH) = 3.0 x 10(4) M(-1)s(-1), k(12)(HFeO(4)(-) + S(-)) = 1.7 x 10(2) M(-1)s(-1), and k(13) (FeO(4)(2-) + SH) = 1.2 x 10(0) M(-1)s(-1). The energy of activation at pH 7.0 was found to be 1.86+/-0.04 kJ mol(-1). If excess potassium ferrate(VI) concentration (10 microM) is used than the SMX in water, the half-life of the reaction using a rate constant obtained in our study would be approximately 2 min at pH 7. The reaction rates are pH dependent; thus, so are the half-lives of the reactions. The results suggest that K(2)FeO(4) has the potential to serve as an oxidative treatment chemical for removing SMX in water. PMID:15950258

  18. Assessing the availability of the teratogenic drug isotretinoin outside the pregnancy prevention programme: a survey of e-pharmacies†

    PubMed Central

    Lagan, Briege M; Dolk, Helen; White, Bronagh; Uges, Donald R A; Sinclair, M

    2014-01-01

    Purpose The increase in online purchasing of medications raises safety concerns regarding teratogenic drugs. The use of the teratogenic drug ‘isotretinoin’ for women of childbearing age requires strict adherence to the Pregnancy Prevention Programme (PPP), a risk minimisation measure imposed on prescribers and users. We sought to determine how readily consumers can purchase isotretinoin online and the associated safety procedures and information. Methods A descriptive cross-sectional survey was conducted of 50 e-pharmacies identified from commonly used search engines. E-pharmacy characteristics and isotretinoin PPP specific criteria were evaluated. Purchases of isotretinoin from seven e-pharmacies not bearing authentication logos and not requiring a prescription were assessed for PPP policy adherence, purchasing procedures and compound quality. Results Forty-three (86%) of the e-pharmacies did not have an authentication seal/logo. Isotretinoin could be purchased from 42 sites without a valid prescription. Information on isotretinoin causing birth defects was lacking in 25 of the 50 sites, on not taking isotretinoin in pregnancy in 24 sites and not taking isotretinoin if planning or at risk of a pregnancy in 33 sites. Of the eight attempted purchases, seven arrived, all without any patient information leaflet. All were verified as isotretinoin. Conclusion The Internet provides a loophole for purchasing of medications known to cause congenital abnormalities, which needs to be addressed by medicines regulatory agencies worldwide. The current PPP for isotretinoin may be failing to protect mothers and babies from preventable harm—clinicians need to be aware of this, and the public needs to be educated about the potential risks. PMID:24493556

  19. Assessment of function and clinical utility of alcohol and other drug web sites: An observational, qualitative study

    PubMed Central

    2011-01-01

    Background The increasing popularity and use of the internet makes it an attractive option for providing health information and treatment, including alcohol/other drug use. There is limited research examining how people identify and access information about alcohol or other drug (AOD) use online, or how they assess the usefulness of the information presented. This study examined the strategies that individuals used to identify and navigate a range of AOD websites, along with the attitudes concerning presentation and content. Methods Members of the general community in Brisbane and Roma (Queensland, Australia) were invited to participate in a 30-minute search of the internet for sites related to AOD use, followed by a focus group discussion. Fifty one subjects participated in the study across nine focus groups. Results Participants spent a maximum of 6.5 minutes on any one website, and less if the user was under 25 years of age. Time spent was as little as 2 minutes if the website was not the first accessed. Participants recommended that AOD-related websites should have an engaging home or index page, which quickly and accurately portrayed the site's objectives, and provided clear site navigation options. Website content should clearly match the title and description of the site that is used by internet search engines. Participants supported the development of a portal for AOD websites, suggesting that it would greatly facilitate access and navigation. Treatment programs delivered online were initially viewed with caution. This appeared to be due to limited understanding of what constituted online treatment, including its potential efficacy. Conclusions A range of recommendations arise from this study regarding the design and development of websites, particularly those related to AOD use. These include prudent use of text and information on any one webpage, the use of graphics and colours, and clear, uncluttered navigation options. Implications for future website development are discussed. PMID:21545748

  20. Time-serial Assessment of Drug Combination Interventions in a Mouse Model of Colorectal Carcinogenesis Using Optical Coherence Tomography

    PubMed Central

    LeGendre-McGhee, Susan; Rice, Photini S.; Wall, R. Andrew; Sprute, Kyle J.; Bommireddy, Ramireddy; Luttman, Amber M.; Nagle, Raymond B.; Abril, Edward R.; Farrell, Katrina; Hsu, Chiu-Hsieh; Roe, Denise J.; Gerner, Eugene W.; Ignatenko, Natalia A.; Barton, Jennifer K.

    2015-01-01

    Optical coherence tomography (OCT) is a high-resolution, nondestructive imaging modality that enables time-serial assessment of adenoma development in the mouse model of colorectal cancer. In this study, OCT was utilized to evaluate the effectiveness of interventions with the experimental antitumor agent ?-difluoromethylornithine (DFMO) and a nonsteroidal anti-inflammatory drug sulindac during early [chemoprevention (CP)] and late stages [chemotherapy (CT)] of colon tumorigenesis. Biological endpoints for drug interventions included OCT-generated tumor number and tumor burden. Immunochistochemistry was used to evaluate biochemical endpoints [Ki-67, cleaved caspase-3, cyclooxygenase (COX)-2, ?-catenin]. K-Ras codon 12 mutations were studied with polymerase chain reaction-based technique. We demonstrated that OCT imaging significantly correlated with histological analysis of both tumor number and tumor burden for all experimental groups (P < 0.0001), but allows more accurate and full characterization of tumor number and burden growth rate because of its time-serial, nondestructive nature. DFMO alone or in combination with sulindac suppressed both the tumor number and tumor burden growth rate in the CP setting because of DFMO-mediated decrease in cell proliferation (Ki-67, P < 0.001) and K-RAS mutations frequency (P = 0.04). In the CT setting, sulindac alone and DFMO/sulindac combination were effective in reducing tumor number, but not tumor burden growth rate. A decrease in COX-2 staining in DFMO/sulindac CT groups (COX-2, P < 0.01) confirmed the treatment effect. Use of nondestructive OCT enabled repeated, quantitative evaluation of tumor number and burden, allowing changes in these parameters to be measured during CP and as a result of CT. In conclusion, OCT is a robust minimally invasive method for monitoring colorectal cancer disease and effectiveness of therapies in mouse models. PMID:26396545

  1. [The development from drug to designer drug.

    PubMed

    Askaa, Bjarke; Horwitz, Henrik; Wøien, Vidar André; Høgberg, Lotte C G; Jürgens, Gesche

    2014-10-13

    Synthetic "designer drugs" with hallucinogenic properties have become increasingly popular among recreational drug users in recent years. Some of the designer drugs are chemically modified drugs previously used in treatment of depression and chronic fatigue. The drugs are available from a large number of internet distributers. There is very little knowledge of the clinical symptoms and how intoxicated people should be treated. We present a review of published literature (including 284 intoxicated patients) and experiences from the Danish poison centre concerning two chemical derivatives of earlier registered drugs. PMID:25316367

  2. Principles for consistent value assessment and sustainable funding of orphan drugs in Europe.

    PubMed

    Gutierrez, Laura; Patris, Julien; Hutchings, Adam; Cowell, Warren

    2015-01-01

    The European Orphan Medicinal Products (OMP) Regulation has successfully encouraged research to develop treatments for rare diseases resulting in the authorisation of new OMPs in Europe. While decisions on OMP designation and marketing authorisation are made at the European Union level, reimbursement decisions are made at the national level. OMP value and affordability are high priority issues for policymakers and decisions regarding their pricing and funding are highly complex. There is currently no European consensus on how OMP value should be assessed and inequalities of access to OMPs have previously been observed. Against this background, policy makers in many countries are considering reforms to improve access to OMPs. This paper proposes ten principles to be considered when undertaking such reforms, from the perspective of an OMP manufacturer. We recommend the continued prioritisation of rare diseases by policymakers, an increased alignment between payer and regulatory frameworks, pricing centred on OMP value, and mechanisms to ensure long-term financial sustainability allowing a continuous and virtuous development of OMPs. Our recommendations support the development of more consistent frameworks and encourage collaboration between all stakeholders, including research-based industry, payers, clinicians, and patients. PMID:25935555

  3. Counterfeit Drug Penetration into Global Legitimate Medicine Supply Chains: A Global Assessment

    PubMed Central

    Mackey, Tim K.; Liang, Bryan A.; York, Peter; Kubic, Thomas

    2015-01-01

    Counterfeit medicines are a global public health risk. We assess counterfeit reports involving the legitimate supply chain using 2009–2011 data from the Pharmaceutical Security Institute Counterfeit Incident System (PSI CIS) database that uses both open and nonpublic data sources. Of the 1,510 identified CIS reports involving counterfeits, 27.6% reported China as the source country of the incident/detection. Further, 51.3% were reported as counterfeit but the specific counterfeit subcategory was not known or verifiable. The most prevalent therapeutic category was anti-infectives (21.1%) with most reports originating from health-related government agencies. Geographically, Asian and Latin American regions and, economically, middle-income markets were most represented. A total of 127 (64.8%) of a total of 196 countries had no legitimate supply chain CIS counterfeit reports. Improvements in surveillance, including detection of security breaches, data collection, analysis, and dissemination are urgently needed to address public health needs to combat the global counterfeit medicines trade. PMID:25897059

  4. Atmospheric Ozone 1985. Assessment of our understanding of the processes controlling its present distribution and change, volume 3

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Topics addressed include: assessment models; model predictions of ozone changes; ozone and temperature trends; trace gas effects on climate; kinetics and photchemical data base; spectroscopic data base (infrared to microwave); instrument intercomparisons and assessments; and monthly mean distribution of ozone and temperature.

  5. Kriging method evaluation for assessing the spatial distribution of urban soil lead contamination.

    PubMed

    Cattle, Julie A; McBratney, Alex B; Minasny, Budiman

    2002-01-01

    Describing contaminant spatial distribution is an integral component of risk assessment. Application of geostatistical techniques for this purpose has been demonstrated previously. These techniques may provide both an estimate of the concentration at a given unsampled location, as well as the probability that the concentration at that location will exceed a critical threshold concentration. This research is a comparative study between multiple indicator kriging and kriging with the cumulative distribution function of order statistics, with both local and global variograms. The aim was to determine which of the four methods is best able to delineate between "contaminated" and "clean" soil. The four methods were validated with a subset of data values that were not used in the prediction. Method performance was assessed by calculating the root mean square error (RMSE), analysis of variance, the proportion of sites misclassified by each method as either "clean" when they were actually "contaminated" or vice versa, and the expected loss for each misclassification type. The data used for the comparison were 807 topsoil Pb concentrations from the inner-Sydney suburbs of Glebe and Camperdown, Australia. While there was very little difference between the four methods, multiple indicator kriging was found to produce the most accurate predictions for delineating "clean" from "contaminated" soil. PMID:12371175

  6. In Vitro Method To Assess Soil Arsenic Metabolism by Human Gut Microbiota: Arsenic Speciation and Distribution.

    PubMed

    Yin, Naiyi; Zhang, Zhennan; Cai, Xiaolin; Du, Huili; Sun, Guoxin; Cui, Yanshan

    2015-09-01

    Arsenic (As) speciation and distribution are two important factors in assessing human health risk from As-contaminated soil. In this study, we used the combination of physiologically based extraction test (PBET) and Simulator of Human Intestinal Microbial Ecosystem (SHIME) to determine soil As metabolism by human gut microbiota. The results showed that the percentage of soil arsenate [As(V)] transformation reached 22.1-38.2%, while that of arsenite [As(III)] attained 66.5-92.0%; 30.1-56.4% of As(V) transformed was attached to the soil solid phase. In comparison to sequential extraction results, almost all amorphous Fe/Al-oxide-bound As was liberated in the colon phase. An X-ray absorption near-edge structure (XANES) showed that the As(III) percentage in the soil solid phase reached 16.6-26.9% and reached 73.4% (soil 1) in the colon phase. Additionally, plenty of As(III) and different extents of methylation were also observed in colon extraction solution. As bioaccessibility in the colon phase was 1.8-2.8 times that in the small intestinal phase. Our results indicated that human gut microbiota increased As bioaccessibility, and large amounts of As(III) were adsorbed onto the soil solid phase as a result of microbial reduction. Determining As speciation and distribution in extraction solution and soil solid phases will allow for an accurate assessment of the risk to human health upon soil As exposure. PMID:26248026

  7. Application of empirical hydration distribution functions around polar atoms for assessing hydration structures of proteins

    NASA Astrophysics Data System (ADS)

    Matsuoka, Daisuke; Nakasako, Masayoshi

    2013-06-01

    To quantitatively characterize hydrogen-bond geometry in local hydration structures of proteins, we constructed a set of empirical hydration distribution functions (EHDFs) around polar protein atoms in the main and side chains of 11 types of hydrophilic amino acids (D. Matsuoka, M. Nakasako, Journal of Physical Chemistry B 113 (2009) 11274). The functions are the ensemble average of possible hydration patterns around the polar atoms, and describe the anisotropic deviations from ideal hydrogen bond geometry. In addition, we defined probability distribution function of hydration water molecules (PDFH) over the hydrophilic surface of a protein as the sum of EHDFs of solvent accessible polar protein atoms. The functions envelop most of hydration sites identified in crystal structures of proteins (D. Matsuoka, M. Nakasako, Journal of Physical Chemistry B 114 (2010) 4652). Here we propose the application of EHDFs and PDFHs for assessing crystallographically identified hydration structures of proteins. First, hydration water molecules are classified with respect to the geometry in hydrogen bonds in referring EHDFs. Difference Fourier electron density map weighted by PDFH of protein is proposed to identify easily density peaks as candidates of hydration water molecules. A computer program implementing those ideas was developed and used for assessing hydration structures of proteins.

  8. Design of the National Water-Quality Assessment Program; occurrence and distribution of water-quality conditions

    USGS Publications Warehouse

    Gilliom, Robert J.; Alley, William M.; Gurtz, Martin E.

    1995-01-01

    The National Water-Quality Assessment Program assesses the status of and trends in the quality of the Nation's ground- and surface-water resources. The occurrence and distribution assessment component characterizes broad-scale water-quality conditions in relation to major contaminant sources and background conditions in each study area. The surface-water design focuses on streams. The ground-water design focuses on major aquifers, with emphasis on recently recharged ground water associated with human activities.

  9. Assessment of anti-atherogenic drugs in vivo and reconstitution of lipoproteins using radioiodinated cholesteryl iopanoate

    SciTech Connect

    DeGalan, M.R.

    1987-01-01

    A nonhydrolyzable radioiodinated cholesteryl ester, 125I-cholesteryl iopanoate (125I-Cl), was found to accumulate in high concentrations in atherosclerotic aortas of cholesterol-fed rabbits after intravenous administration. Aortas from normal chow-fed rabbits did not exhibit significant 125I-Cl accumulation. When cholesterol-fed rabbits were intravenously administered Tween-solubilized 125I-Cl and simultaneously treated with either of two anti-atherogenic compounds, estradiol 17..beta..-cypionate or colestipol, the extent of aortic atherosclerosis was found to dramatically decrease. Measurement of aortic radioactivity was found to strongly correlate with the severity of atherosclerosis. Although the specificity of 125I-Cl for atheromatous lesions was very good, gamma-camera scintigraphy of the abdomens of these rabbits 6 days after cessation of 125I-Cl administration was not able to consistently predict the severity of atherosclerosis. Tissue distribution studies suggested that high blood and spinal column bone marrow radioactivity produced aorta:nontarget radioactivity ratios unfavorable with respect to imaging. To improve this ratio so as to permit noninvasive imaging, attempts were made to incorporate 125I-Cl into serum lipoproteins. Labelling of either rabbit LDL by in vivo incorporation or human LDL by transfer of 125I-Cl from liposomes using cholesteryl ester transfer protein resulted in lipoproteins with low specific activity. Higher specific activity was achieved by reconstituting delipidated human LDL with a mixture of 125I-Cl and unlabeled cholesteryl oleate. These particles were taken up in high amounts by monolayers of human fibroblasts but not by fibroblasts deficient in LDL receptors or by normal fibroblasts during competition with unlabeled native LDL.

  10. Systematic assessment of analytical methods for drug sensitivity prediction from cancer cell line data.

    PubMed

    Jang, In Sock; Neto, Elias Chaibub; Guinney, Juistin; Friend, Stephen H; Margolin, Adam A

    2014-01-01

    Large-scale pharmacogenomic screens of cancer cell lines have emerged as an attractive pre-clinical system for identifying tumor genetic subtypes with selective sensitivity to targeted therapeutic strategies. Application of modern machine learning approaches to pharmacogenomic datasets have demonstrated the ability to infer genomic predictors of compound sensitivity. Such modeling approaches entail many analytical design choices; however, a systematic study evaluating the relative performance attributable to each design choice is not yet available. In this work, we evaluated over 110,000 different models, based on a multifactorial experimental design testing systematic combinations of modeling factors within several categories of modeling choices, including: type of algorithm, type of molecular feature data, compound being predicted, method of summarizing compound sensitivity values, and whether predictions are based on discretized or continuous response values. Our results suggest that model input data (type of molecular features and choice of compound) are the primary factors explaining model performance, followed by choice of algorithm. Our results also provide a statistically principled set of recommended modeling guidelines, including: using elastic net or ridge regression with input features from all genomic profiling platforms, most importantly, gene expression features, to predict continuous-valued sensitivity scores summarized using the area under the dose response curve, with pathway targeted compounds most likely to yield the most accurate predictors. In addition, our study provides a publicly available resource of all modeling results, an open source code base, and experimental design for researchers throughout the community to build on our results and assess novel methodologies or applications in related predictive modeling problems. PMID:24297534

  11. Lymphatic filariasis in Papua New Guinea: distribution at district level and impact of mass drug administration, 1980 to 2011

    PubMed Central

    2013-01-01

    Background Lymphatic filariasis (LF) caused by Wuchereria bancrofti is present at high prevalence in some parts of Papua New Guinea. However, there has been no rigorous data-based representative assessment of nationwide prevalence of LF. The LF programme has been daunted by the scope of the problem, and progress on mass drug administration (MDA) has been slow and lacking in resources. Methods A systematic literature review identified LF surveys in Papua New Guinea between 1980 and 2011. Results were extracted by location, time period and test used (blood slide, immunochromatographic test (ICT) or Og4C3 ELISA) and combined by district. Three criteria schemes based on the Global Programme to Eliminate Lymphatic Filariasis guidelines, with modifications, were developed to classify and prioritize districts by prevalence level. Results of repeated surveys in the same sites were used to investigate the impact of MDA on LF prevalence over the time period. Results There were 312 distinct survey sites identified in 80 of the 89 districts over the 31-year period. The overall LF prevalence in the sites tested was estimated at 18.5 to 27.5% by blood slide for microfilariae (Mf), 10.1% to 12.9% by ICT and 45.4% to 48.8% by Og4C3. Biases in site selection towards areas with LF, and change in type of assay used, affected the prevalence estimates, but overall decline in prevalence over the time period was observed. Depending on the criteria used, 34 to 36 districts (population 2.7 to 2.9 million) were classed as high endemic (?5% prevalence), 15 to 25 districts (1.7 to 1.9 million) as low endemic (<5%) and 20 to 31 (1.3 to 2.2 million) as non-endemic. Nine districts (0.7 million) had no information. The strong impact of MDA, especially on microfilaria (Mf) prevalence, was noted in sites with repeat surveys. Conclusions This analytical review of past surveys of LF in Papua New Guinea enables better estimation of the national burden, identifies gaps in knowledge, quantifies and locates the population at risk, and can be used to predict the likely impact of MDA and/or vector control. Better targeting of districts by level of prevalence will strengthen the control programme, facilitate monitoring of the disease trend and increase the likelihood of reaching the target of LF elimination by 2020. PMID:23311302

  12. A microcomputer program for energy assessment and aggregation using the triangular probability distribution

    NASA Astrophysics Data System (ADS)

    Crovelli, Robert A.; Balay, Richard H.

    A general risk-analysis method was developed for petroleum-resource assessment and other applications. The triangular probability distribution is used as a model with an analytic aggregation methodology based on probability theory rather than Monte-Carlo simulation. Among the advantages of the analytic method are its computational speed and flexibility, and the saving of time and cost on a microcomputer. The input into the model consists of a set of components (e.g. geologic provinces) and, for each component, three potential resource estimates: minimum, most likely (mode), and maximum. Assuming a triangular probability distribution, the mean, standard deviation, and seven fractiles ( F100, F95, F75, F50, F25, F5, and F0) are computed for each component, where for example, the probability of more than F95 is equal to 0.95. The components are aggregated by combining the means, standard deviations, and respective fractiles under three possible siutations (1) perfect positive correlation, (2) complete independence, and (3) any degree of dependence between these two polar situations. A package of computer programs named the TRIAGG system was written in the Turbo Pascal 4.0 language for performing the analytic probabilistic methodology. The system consists of a program for processing triangular probability distribution assessments and aggregations, and a separate aggregation routine for aggregating aggregations. The user's documentation and program diskette of the TRIAGG system are available from USGS Open File Services. TRIAGG requires an IBM-PC/XT/AT compatible microcomputer with 256kbyte of main memory, MS-DOS 3.1 or later, either two diskette drives or a fixed disk, and a 132 column printer. A graphics adapter and color display are optional.

  13. A microcomputer program for energy assessment and aggregation using the triangular probability distribution

    USGS Publications Warehouse

    Crovelli, R.A.; Balay, R.H.

    1991-01-01

    A general risk-analysis method was developed for petroleum-resource assessment and other applications. The triangular probability distribution is used as a model with an analytic aggregation methodology based on probability theory rather than Monte-Carlo simulation. Among the advantages of the analytic method are its computational speed and flexibility, and the saving of time and cost on a microcomputer. The input into the model consists of a set of components (e.g. geologic provinces) and, for each component, three potential resource estimates: minimum, most likely (mode), and maximum. Assuming a triangular probability distribution, the mean, standard deviation, and seven fractiles (F100, F95, F75, F50, F25, F5, and F0) are computed for each component, where for example, the probability of more than F95 is equal to 0.95. The components are aggregated by combining the means, standard deviations, and respective fractiles under three possible siutations (1) perfect positive correlation, (2) complete independence, and (3) any degree of dependence between these two polar situations. A package of computer programs named the TRIAGG system was written in the Turbo Pascal 4.0 language for performing the analytic probabilistic methodology. The system consists of a program for processing triangular probability distribution assessments and aggregations, and a separate aggregation routine for aggregating aggregations. The user's documentation and program diskette of the TRIAGG system are available from USGS Open File Services. TRIAGG requires an IBM-PC/XT/AT compatible microcomputer with 256kbyte of main memory, MS-DOS 3.1 or later, either two diskette drives or a fixed disk, and a 132 column printer. A graphics adapter and color display are optional. ?? 1991.

  14. Parenting quality in drug-addicted mothers in a therapeutic mother–child community: the contribution of attachment and personality assessment

    PubMed Central

    De Palo, Francesca; Capra, Nicoletta; Simonelli, Alessandra; Salcuni, Silvia; Di Riso, Daniela

    2014-01-01

    Growing evidence shows that attachment is a key risk factor for the diagnosis and treatment of clinical diseases in Axis I, such as drug addiction. Recent literature regarding attachment, psychiatric pathology, and drug addiction demonstrates that there is a clear prevalence of insecure attachment patterns in clinical and drug addicted subjects. Specifically, some authors emphasize that the anxious-insecure attachment pattern is prevalent among drug-addicted women with double diagnosis (Fonagy et al., 1996). The construct of attachment as a risk factor in clinical samples of drug-addicted mothers needs to be studied more in depth though. The present explorative study focused on the evaluation of parenting quality in a therapeutic mother–child community using attachment and personality assessment tools able to outline drug-addicted mothers’ profiles. This study involved 30 drug addicted mothers, inpatients of a therapeutic community (TC). Attachment representations were assessed via the Adult Attachment Interview; personality diagnosis and symptomatic profiles were performed using the Structured Clinical Interview of the DSM-IV (SCID-II) and the Symptom Check List-90-R (SCL-90-R), respectively. Both instruments were administered during the first six months of residence in a TC. Results confirmed the prevalence of insecure attachment representations (90%), with a high presence of U patterns, prevalently scored for dangerous and/or not protective experiences in infanthood. Very high values (>5) were found for some experience scales (i.e., neglect and rejection scales). Data also showed very low values (1–3) in metacognitive monitoring, coherence of transcript and coherence of mind scales. Patients’ different profiles (U vs. E vs. Ds) were linked to SCID-II diagnosis, providing insightful indications both for treatment planning and intervention on parenting functions and for deciding if to start foster care or adoption proceedings for children. PMID:25309481

  15. What Matters Most? Assessing the Influence of Demographic Characteristics, College-Specific Risk Factors, and Poly-Drug Use on Nonmedical Prescription Drug Use

    ERIC Educational Resources Information Center

    Lanier, Christina; Farley, Erin J.

    2011-01-01

    Objective: Although prior recent research has revealed a significant relationship between the nonmedical use of prescription drugs, demographic characteristics, college-specific risk factors, and other substance use among college students, there remains a need to conduct a comparative analysis on the differential impact these factors may have on…

  16. Common Data Models and Efficient Reproducible Workflows for Distributed Ocean Model Skill Assessment

    NASA Astrophysics Data System (ADS)

    Signell, R. P.; Snowden, D. P.; Howlett, E.; Fernandes, F. A.

    2014-12-01

    Model skill assessment requires discovery, access, analysis, and visualization of information from both sensors and models, and traditionally has been possible only by a few experts. The US Integrated Ocean Observing System (US-IOOS) consists of 17 Federal Agencies and 11 Regional Associations that produce data from various sensors and numerical models; exactly the information required for model skill assessment. US-IOOS is seeking to develop documented skill assessment workflows that are standardized, efficient, and reproducible so that a much wider community can participate in the use and assessment of model results. Standardization requires common data models for observational and model data. US-IOOS relies on the CF Conventions for observations and structured grid data, and on the UGRID Conventions for unstructured (e.g. triangular) grid data. This allows applications to obtain only the data they require in a uniform and parsimonious way using web services: OPeNDAP for model output and OGC Sensor Observation Service (SOS) for observed data. Reproducibility is enabled with IPython Notebooks shared on GitHub (http://github.com/ioos). These capture the entire skill assessment workflow, including user input, search, access, analysis, and visualization, ensuring that workflows are self-documenting and reproducible by anyone, using free software. Python packages for common data models are Pyugrid and the British Met Office Iris package. Python packages required to run the workflows (pyugrid, pyoos, and the British Met Office Iris package) are also available on GitHub and on Binstar.org so that users can run scenarios using the free Anaconda Python distribution. Hosted services such as Wakari enable anyone to reproduce these workflows for free, without installing any software locally, using just their web browser. We are also experimenting with Wakari Enterprise, which allows multi-user access from a web browser to an IPython Server running where large quantities of model output reside, increasing the efficiency. The open development and distribution of these workflows, and the software on which they depend, is an educational resource for those new to the field and a center of focus where practitioners can contribute new software and ideas.

  17. Discussion on the influence of truncation of ground motion residual distribution on probabilistic seismic hazard assessment

    NASA Astrophysics Data System (ADS)

    Wu, Jian; Gao, Mengtan; Chen, Kun; Huang, Bei

    2011-09-01

    Recent studies on assessment of a very low annual probability of exceeding (APE) ground motions, 10-4 or less, have highlighted the importance of the upper bound of ground motions when very low probability results are acquired. The truncation level adopted in probabilistic seismic hazard analysis (PSHA) should be determined by an aleatory uncertainty model (i.e., distribution model) of ground motions and the possible maximum and minimum ground motion values of a specific earthquake. However, at the present time, it is impossible to establish the upper bound model for ground motions based on the source characteristics and/or ground motion propagation. McGuire suggested a truncation level be fixed at a number of ? = 6, or the distribution of residuals be truncated in such a manner that site intensity cannot be greater than the epicenter intensity. This study aims to find a reasonable and feasible truncation level to be used in PSHA when the physical mechanism is not available to find the extreme ground motion. A mathematical analysis of the influence of the truncation level on PSHA, case studies of sites in different seismotectonic settings, and a distribution analysis of ground motion residuals are conducted in this study. It is concluded that ? = 4 is the minimum acceptable value for engineering applications for APEs within 0.002 to 10-4, and for low APEs, such as 10-5 and 10-6, the value of ? should be no less than 5 in most regions of China.

  18. Use of sinkhole and specific capacity distributions to assess vertical gradients in a karst aquifer

    USGS Publications Warehouse

    McCoy, K.J.; Kozar, M.D.

    2008-01-01

    The carbonate-rock aquifer in the Great Valley, West Virginia, USA, was evaluated using a database of 687 sinkholes and 350 specific capacity tests to assess structural, lithologic, and topographic influences on the groundwater flow system. The enhanced permeability of the aquifer is characterized in part by the many sinkholes, springs, and solutionally enlarged fractures throughout the valley. Yet, vertical components of subsurface flow in this highly heterogeneous aquifer are currently not well understood. To address this problem, this study examines the apparent relation between geologic features of the aquifer and two spatial indices of enhanced permeability attributed to aquifer karstification: (1) the distribution of sinkholes and (2) the occurrence of wells with relatively high specific capacity. Statistical results indicate that sinkholes (funnel and collapse) occur primarily along cleavage and bedding planes parallel to subparallel to strike where lateral or downward vertical gradients are highest. Conversely, high specific capacity values are common along prominent joints perpendicular or oblique to strike. The similarity of the latter distribution to that of springs suggests these fractures are areas of upward-convergent flow. These differences between sinkhole and high specific capacity distributions suggest vertical flow components are primarily controlled by the orientation of geologic structure and associated subsurface fracturing. ?? 2007 Springer-Verlag.

  19. Independent Orbiter Assessment (IOA): Assessment of the electrical power generation/power reactant storage and distribution subsystem FMEA/CIL

    NASA Technical Reports Server (NTRS)

    Ames, B. E.

    1988-01-01

    The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) is presented. The IOA effort first completed an analysis of the Electrical Power Generation/Power Reactant Storage and Distribution (EPG/PRSD) subsystem hardware, generating draft failure modes and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The IOA results were then compared to the NASA FMEA/CIL baselines with proposed Post 51-L updates included. A resolution of each discrepancy from the comparison is provided through additional analysis as required. The results of that comparison are documented for the Orbiter EPG/PRSD hardware. The comparison produced agreement on all but 27 FMEAs and 9 CIL items. The discrepancy between the number of IOA findings and NASA FMEAs can be partially explained by the different approaches used by IOA and NASA to group failure modes together to form one FMEA. Also, several IOA items represented inner tank components and ground operations failure modes which were not in the NASA baseline.

  20. Affordable non-traditional source data mining for context assessment to improve distributed fusion system robustness

    NASA Astrophysics Data System (ADS)

    Bowman, Christopher; Haith, Gary; Steinberg, Alan; Morefield, Charles; Morefield, Michael

    2013-05-01

    This paper describes methods to affordably improve the robustness of distributed fusion systems by opportunistically leveraging non-traditional data sources. Adaptive methods help find relevant data, create models, and characterize the model quality. These methods also can measure the conformity of this non-traditional data with fusion system products including situation modeling and mission impact prediction. Non-traditional data can improve the quantity, quality, availability, timeliness, and diversity of the baseline fusion system sources and therefore can improve prediction and estimation accuracy and robustness at all levels of fusion. Techniques are described that automatically learn to characterize and search non-traditional contextual data to enable operators integrate the data with the high-level fusion systems and ontologies. These techniques apply the extension of the Data Fusion & Resource Management Dual Node Network (DNN) technical architecture at Level 4. The DNN architecture supports effectively assessment and management of the expanded portfolio of data sources, entities of interest, models, and algorithms including data pattern discovery and context conformity. Affordable model-driven and data-driven data mining methods to discover unknown models from non-traditional and `big data' sources are used to automatically learn entity behaviors and correlations with fusion products, [14 and 15]. This paper describes our context assessment software development, and the demonstration of context assessment of non-traditional data to compare to an intelligence surveillance and reconnaissance fusion product based upon an IED POIs workflow.

  1. Distributed temperature sensing (DTS) as an ecological assessment tool in stream environments

    NASA Astrophysics Data System (ADS)

    Hatch, C. E.; Tyler, S. W.; Boughton, D.; Belica, L.

    2009-12-01

    Temperature has long been used as an indicator of ecosystem health and suitability for aquatic species, particularly in sensitive areas crucial to the survival of declining important fish populations. Typically, temperature surveys are of long duration but very limited in spatial extent. In recent years, considerable attention has been paid to assessing the ecology, and particularly the thermal regimes, of remaining near-pristine headwater catchments. These studies hope to assess habitats for native species restoration and identify key stream reaches where reproduction takes place, as well as seasonal thermal refugia supporting species survival and local thermal heterogeneities in larger stream systems that allow migratory pathways to persist. Raman-spectra distributed temperature sensing (DTS) along fiber-optic cables provides a unique opportunity to measure continuous longitudinal stream temperatures for hundreds of meters, allowing researchers to assess groundwater inflows, thermal refugia, and temperature heterogeneities at an extremely detailed spatial scale. In this compilation of studies, we present data from three semi-arid catchments (Strawberry Creek in the Great Basin, Squaw Creek the Sierra Nevada, and Horse Creek in the coastal range of California) to investigate seasonal and diurnal thermal behavior, the feedback between hydrology, geology and ecosystem function, and most importantly, the identification and spatial variability of thermal refugia.

  2. Relationship Between Drug Discrimination and Ratings of Subjective Effects: Implications for Assessing and Understanding the Abuse Potential of d-Amphetamine in Humans

    PubMed Central

    Reynolds, Anna R.; Bolin, B. Levi; Stoops, William W.; Rush, Craig R.

    2014-01-01

    The discriminative and subjective effects of drugs in humans are related, but the full extent of this relationship remains to be determined. To further explore this relationship, a retrospective analysis was conducted on data from six studies completed in our laboratory that used identical procedures. The relationship between the discriminative and subjective effects of a range of doses of d-amphetamine (i.e., 2.5–15 mg) was examined using correlational analyses. Significant correlations with discrimination performance were observed on 15 of 20 items from the Drug-Effect Questionnaire across a range of qualities (e.g., Pay For [a positive effect indicative of abuse potential] and Active [a stimulant-like effect]), but the magnitude of these relationships was modest (r < 0.52). The current findings demonstrate that diverse subjective effects contribute to the discriminative effects of d-amphetamine and indicate that the former are a more practical means to assess abuse potential of drugs. Although these procedures are fundamentally related in that they rely on the presence of an interoceptive drug state, they differ in the dimension(s) of the interoceptive effects that participants must quantify. The simultaneous use of drug discrimination and subjective effects may, therefore, reveal complimentary aspects of drug effects that underlie their potential for abuse. PMID:23851485

  3. In Vitro Infectivity Assessment by Drug Susceptibility Comparison of Recombinant Leishmania major Expressing Enhanced Green Fluorescent Protein or EGFP-Luciferase Fused Genes with Wild-Type Parasite

    PubMed Central

    Sadeghi, Somayeh; Seyed, Negar; Etemadzadeh, Mohammad-Hossein; Abediankenari, Saeid; Rafati, Sima; Taheri, Tahereh

    2015-01-01

    Leishmaniasis is a worldwide uncontrolled parasitic disease due to the lack of effective drug and vaccine. To speed up effective drug development, we need powerful methods to rapidly assess drug effectiveness against the intracellular form of Leishmania in high throughput assays. Reporter gene technology has proven to be an excellent tool for drug screening in vitro. The effects of reporter proteins on parasite infectivity should be identified both in vitro and in vivo. In this research, we initially compared the infectivity rate of recombinant Leishmania major expressing stably enhanced green fluorescent protein (EGFP) alone or EGFP-luciferase (EGFP-LUC) with the wild-type strain. Next, we evaluated the sensitivity of these parasites to amphotericin B (AmB) as a standard drug in 2 parasitic phases, promastigote and amastigote. This comparison was made by MTT and nitric oxide (NO) assay and by quantifying the specific signals derived from reporter genes like EGFP intensity and luciferase activity. To study the amastigote form, both B10R and THP-1 macrophage cell lines were infected in the stationary phase and were exposed to AmB at different time points. Our results clearly revealed that the 3 parasite lines had similar in vitro infectivity rates with comparable parasite-induced levels of NO following interferon-?/lipopolysaccharide induction. Based on our results we proposed the more reporter gene, the faster and more sensitive evaluation of the drug efficiency. PMID:26323836

  4. In Vitro Infectivity Assessment by Drug Susceptibility Comparison of Recombinant Leishmania major Expressing Enhanced Green Fluorescent Protein or EGFP-Luciferase Fused Genes with Wild-Type Parasite.

    PubMed

    Sadeghi, Somayeh; Seyed, Negar; Etemadzadeh, Mohammad-Hossein; Abediankenari, Saeid; Rafati, Sima; Taheri, Tahereh

    2015-08-01

    Leishmaniasis is a worldwide uncontrolled parasitic disease due to the lack of effective drug and vaccine. To speed up effective drug development, we need powerful methods to rapidly assess drug effectiveness against the intracellular form of Leishmania in high throughput assays. Reporter gene technology has proven to be an excellent tool for drug screening in vitro. The effects of reporter proteins on parasite infectivity should be identified both in vitro and in vivo. In this research, we initially compared the infectivity rate of recombinant Leishmania major expressing stably enhanced green fluorescent protein (EGFP) alone or EGFP-luciferase (EGFP-LUC) with the wild-type strain. Next, we evaluated the sensitivity of these parasites to amphotericin B (AmB) as a standard drug in 2 parasitic phases, promastigote and amastigote. This comparison was made by MTT and nitric oxide (NO) assay and by quantifying the specific signals derived from reporter genes like EGFP intensity and luciferase activity. To study the amastigote form, both B10R and THP-1 macrophage cell lines were infected in the stationary phase and were exposed to AmB at different time points. Our results clearly revealed that the 3 parasite lines had similar in vitro infectivity rates with comparable parasite-induced levels of NO following interferon-?/lipopolysaccharide induction. Based on our results we proposed the more reporter gene, the faster and more sensitive evaluation of the drug efficiency. PMID:26323836

  5. Assessment of the health risks related to the presence of drug residues in water for human consumption: application to carbamazepine.

    PubMed

    Houeto, Paul; Carton, Aude; Guerbet, Michel; Mauclaire, Anne-Cécile; Gatignol, Chantal; Lechat, Philippe; Masset, Dominique

    2012-02-01

    Pharmaceutical residues have been detected at low (usually ng/L) concentrations in drinking water sources. The detection of drugs in water intended for human consumption (WIHC) has raised questions of safety. In the absence of regulatory or other official guidance, water utilities are faced with a problem of which pharmaceutical residues should be monitored and the toxicological limits that should be required. In this essay, we define an approach for the assessment of health risks related to chemicals found in drinking water. We use the examples of carbamazepine and its main metabolite 10,11-epoxycarbamazepine to demonstrate our approach, which involves application of the following algorithm: (1) when there is human or animal toxicity data, a toxicity reference value (TRV) can be calculated; (2) when this is not applicable, an attempt should be made to derive the TRV using known information about the minimum therapeutic dose (MTD); and (3) when no applicable data is available, at all, a threshold of toxicological concern (TTC) should be estimated. In the case of carbamazepine, where relevant toxicological data exists, we derived a TRV, based on the known minimum therapeutic dose (MTD). For carbamazepine's metabolite 10,11-epoxycarbamazepine, there is no toxicological data, so we applied the TTC approach. Using this approach, and combining our estimates with what is known about these chemicals' margin of exposure (MOE), suggests that there is likely to be no appreciable risk to human health exposure to carbamazepine or its major metabolite, even given the inevitable uncertainties in exposure scenarios. PMID:22178769

  6. Determination of the impurities in drug products containing montelukast and in silico/in vitro genotoxicological assessments of sulfoxide impurity.

    PubMed

    Emerce, Esra; Cok, Ismet; Degim, I Tuncer

    2015-10-14

    Impurities affecting safety, efficacy, and quality of pharmaceuticals are of increasing concern for regulatory agencies and pharmaceutical industries, since genotoxic impurities are understood to play important role in carcinogenesis. The study aimed to analyse impurities of montelukast chronically used in asthma theraphy and perform genotoxicological assessment considering regulatory approaches. Impurities (sulfoxide, cis-isomer, Michael adducts-I&II, methylketone, methylstyrene) were quantified using RP-HPLC analysis on commercial products available in Turkish market. For sulfoxide impurity, having no toxicity data and found to be above the qualification limit, in silico mutagenicity prediction analysis, miniaturized bacterial gene mutation test, mitotic index determination and in vitro chromosomal aberration test w/wo metabolic activation system were conducted. In the analysis of different batches of 20 commercial drug products from 11 companies, only sulfoxide impurity exceeded qualification limit in pediatric tablets from 2 companies and in adult tablets from 7 companies. Leadscope and ToxTree programs predicted sulfoxide impurity as nonmutagenic. It was also found to be nonmutagenic in Ames MPF Penta I assay. Sulfoxide impurity was dose-dependent cytotoxic in human peripheral lymphocytes, however, it was found to be nongenotoxic. It was concluded that sulfoxide impurity should be considered as nonmutagenic and can be classified as ordinary impurity according to guidelines. PMID:26205398

  7. Parental Drug Use as Child Abuse

    MedlinePLUS

    ... child 7 • Exposing a child to the criminal sale or distribution of drugs 8 Approximately 33 States ... use in the home environment • The distribution or sale of illegal drugs or drug paraphernalia occurs in ...

  8. Quantifying the chemical beauty of drugs

    NASA Astrophysics Data System (ADS)

    Bickerton, G. Richard; Paolini, Gaia V.; Besnard, Jérémy; Muresan, Sorel; Hopkins, Andrew L.

    2012-02-01

    Drug-likeness is a key consideration when selecting compounds during the early stages of drug discovery. However, evaluation of drug-likeness in absolute terms does not reflect adequately the whole spectrum of compound quality. More worryingly, widely used rules may inadvertently foster undesirable molecular property inflation as they permit the encroachment of rule-compliant compounds towards their boundaries. We propose a measure of drug-likeness based on the concept of desirability called the quantitative estimate of drug-likeness (QED). The empirical rationale of QED reflects the underlying distribution of molecular properties. QED is intuitive, transparent, straightforward to implement in many practical settings and allows compounds to be ranked by their relative merit. We extended the utility of QED by applying it to the problem of molecular target druggability assessment by prioritizing a large set of published bioactive compounds. The measure may also capture the abstract notion of aesthetics in medicinal chemistry.

  9. Distributed Drug Discovery, Part 2: Global Rehearsal of Alkylating Agents for the Synthesis of Resin-Bound Unnatural Amino Acids and Virtual D3 Catalog Construction

    PubMed Central

    2008-01-01

    Distributed Drug Discovery (D3) proposes solving large drug discovery problems by breaking them into smaller units for processing at multiple sites. A key component of the synthetic and computational stages of D3 is the global rehearsal of prospective reagents and their subsequent use in the creation of virtual catalogs of molecules accessible by simple, inexpensive combinatorial chemistry. The first section of this article documents the feasibility of the synthetic component of Distributed Drug Discovery. Twenty-four alkylating agents were rehearsed in the United States, Poland, Russia, and Spain, for their utility in the synthesis of resin-bound unnatural amino acids 1, key intermediates in many combinatorial chemistry procedures. This global reagent rehearsal, coupled to virtual library generation, increases the likelihood that any member of that virtual library can be made. It facilitates the realistic integration of worldwide virtual D3 catalog computational analysis with synthesis. The second part of this article describes the creation of the first virtual D3 catalog. It reports the enumeration of 24?416 acylated unnatural amino acids 5, assembled from lists of either rehearsed or well-precedented alkylating and acylating reagents, and describes how the resulting catalog can be freely accessed, searched, and downloaded by the scientific community. PMID:19105725

  10. Nutrients distribution and trophic status assessment in the northern Beibu Gulf, China

    NASA Astrophysics Data System (ADS)

    Lai, Junxiang; Jiang, Fajun; Ke, Ke; Xu, Mingben; Lei, Fu; Chen, Bo

    2014-09-01

    Using historical and 2010 field data, the distribution of nutrients in the northern Beibu Gulf of China is described. There was a decreasing trend in the concentration of nutrients from the north coast to offshore waters of the northern Beibu Gulf, reflecting the influence of inputs from land-based sources. High concentrations of dissolved inorganic nitrogen (DIN) and phosphate (PO4-P) occurred mainly at Fangchenggang Bay, Qinzhou Bay, and Lianzhou Bay. Four different methods were used to assess eutrophication. The trophic status of the Beibu Gulf was characterized using the single factor, Eutrophication index (EI), Trophic index (TRIX) and Assessment of Estuarine Trophic Status (ASSETS) methods. Based on nutrient concentrations, 73.9% of DIN and 26.7% of PO4-P samples exceeded the fourth grade Seawater Quality Standard of China. Eutrophication index values varied widely, but higher levels of eutrophication were generally found in bays and estuaries. TRIX values ranged from 2.61 to 7.27, with an average of 4.98, indicating a mesotrophic and moderately productive system. A positive correlation between TRIX and harmful algal species richness and abundance was observed. The ASSETS model evaluates eutrophication status based on a Pressure-State-Response approach, including three main indices: influencing factors, overall eutrophic condition, and future outlook. The Beibu Gulf was graded as moderate using ASSETS. The single factor and Chinese nutrient index methods were considered inadequate for the assessment of trophic status. TRIX can be used as an indicator of trophic state and ASSETS showed good potential to assess eutrophication. The results of TRIX and ASSETS depend on threshold values. To establish these values, further research is required within the northern Beibu Gulf.

  11. Metabolic Drug-Drug Interaction Potential of Macrolactin A and 7-O-Succinyl Macrolactin A Assessed by Evaluating Cytochrome P450 Inhibition and Induction and UDP-Glucuronosyltransferase Inhibition In Vitro

    PubMed Central

    Bae, Soo Hyeon; Kwon, Min Jo; Park, Jung Bae; Kim, Doyun; Kim, Dong-Hee; Kang, Jae-Seon; Kim, Chun-Gyu; Oh, Euichaul

    2014-01-01

    Macrolactin A (MA) and 7-O-succinyl macrolactin A (SMA), polyene macrolides containing a 24-membered lactone ring, show antibiotic effects superior to those of teicoplanin against vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. MA and SMA are currently being evaluated as antitumor agents in preclinical studies in Korea. We evaluated the potential of MA and SMA for the inhibition or induction of human liver cytochrome P450 (CYP) enzymes and UDP-glucuronosyltransferases (UGTs) in vitro to assess their safety as new molecular entities. We demonstrated that MA and SMA are potent competitive inhibitors of CYP2C9, with Ki values of 4.06 ?M and 10.6 ?M, respectively. MA and SMA also weakly inhibited UGT1A1 activity, with Ki values of 40.1 ?M and 65.3 ?M, respectively. However, these macrolactins showed no time-dependent inactivation of the nine CYPs studied. In addition, MA and SMA did not induce CYP1A2, CYP2B6, or CYP3A4/5. On the basis of an in vitro-in vivo extrapolation, our data strongly suggested that MA and SMA are unlikely to cause clinically significant drug-drug interactions mediated via inhibition or induction of most of the CYPs involved in drug metabolism in vivo, except for the inhibition of CYP2C9 by MA. Similarly, MA and SMA are unlikely to inhibit the activity of UGT1A1, UGT1A4, UGT1A6, UGT1A9, and UGT2B7 enzymes in vivo. Although further investigations will be required to clarify the in vivo interactions of MA with CYP2C9-targeted drugs, our findings offer a clearer understanding and prediction of drug-drug interactions for the safe use of MA and SMA in clinical practice. PMID:24890600

  12. Assessment of the Aerosol Distribution Over Indian Subcontinent in CMIP5 Models

    NASA Astrophysics Data System (ADS)

    Sanap, S. D.; Pandithurai, G.

    2014-12-01

    This paper examines the aerosol distribution over Indian subcontinent as represented in 21 models from Coupled Model Inter-comparison Project Phase 5 (CMIP5) simulations, wherein model simulated aerosol optical depth (AOD) is compared with Moderate Resolution Imaging Spectro-radiometer (MODIS) satellite observations. The objective of the study is to provide an assessment of the capability of various global models, participating in CMIP5 project, in capturing the realistic spatial and temporal distribution of aerosol species over the Indian subcontinent. Results from our analysis show that majority of the CMIP5 models seriously underestimates the spatio-temporal variability of aerosol species over the Indian subcontinent, in particular over Indo-Gangetic Plains(IGP). Though the representation of black carbon (BC) loading in many models is fairly good, the dust loading is observed to be significantly low in majority of the models. The presence of pronounced dust activity over northern India and dust being one of the major constituent of aerosol species, the biases in dust loading has a great impact on the AOD of that region. We found that considerable biases in simulating the 850 hPa wind field (which plays important role in transport of dust from adjacent deserts) would be the possible reason for poor representation of dust AOD and in turn total AOD over Indian region in CMIP5 models. In addition, aerosol radiative forcing (ARF) underestimated/overestimated in most of the models. However, spatial distribution of ARF in multi-model ensemble mean is comparable reasonably well with observations with bias in magnitudes. This analysis emphasizes the fundamental need to improve the representation of aerosol species in current state of the art climate models. As reported in Intergovernmental Panel on Climate Change (IPCC) fourth assessment report (AR4), the level of scientific understanding (LOSU) of climatic impact of aerosols is medium-low. For better understanding of short and long term implications of changing concentrations of aerosol species on climate, it is imperative to have a realistic representation of aerosol distribution over regions with high aerosol loading.

  13. Assessment of the aerosol distribution over Indian subcontinent in CMIP5 models

    NASA Astrophysics Data System (ADS)

    Sanap, S. D.; Ayantika, D. C.; Pandithurai, G.; Niranjan, K.

    2014-04-01

    This paper examines the aerosol distribution over Indian subcontinent as represented in 21 models from Coupled Model Inter-comparison Project Phase 5 (CMIP5) simulations, wherein model simulated aerosol optical depth (AOD) is compared with Moderate Resolution Imaging Spectro-radiometer (MODIS) satellite observations. The objective of the study is to provide an assessment of the capability of various global models, participating in CMIP5 project, in capturing the realistic spatial and temporal distribution of aerosol species over the Indian subcontinent. Results from our analysis show that majority of the CMIP5 models (excepting HADGEM2-ES, HADGEM2-CC) seriously underestimates the spatio-temporal variability of aerosol species over the Indian subcontinent, in particular over Indo-Gangetic Plains (IGP). Since IGP region is dominated by anthropogenic activities, high population density, and wind driven transport of dust and other aerosol species, MODIS observations reveal high AOD values over this region. Though the representation of black carbon (BC) loading in many models is fairly good, the dust loading is observed to be significantly low in majority of the models. The presence of pronounced dust activity over northern India and dust being one of the major constituent of aerosol species, the biases in dust loading has a great impact on the AOD of that region. We found that considerable biases in simulating the 850 hPa wind field (which plays important role in transport of dust from adjacent deserts) would be the possible reason for poor representation of dust AOD and in turn total AOD over Indian region in CMIP5 models. In addition, aerosol radiative forcing (ARF) underestimated/overestimated in most of the models. However, spatial distribution of ARF in multi-model ensemble mean is comparable reasonably well with observations with bias in magnitudes. This analysis emphasizes the fundamental need to improve the representation of aerosol species in current state of the art climate models. As reported in Intergovernmental Panel on Climate Change (IPCC) fourth assessment report (AR4), the level of scientific understanding (LOSU) of climatic impact of aerosols is medium-low. For better understanding of short and long term implications of changing concentrations of aerosol species on climate, it is imperative to have a realistic representation of aerosol distribution over regions with high aerosol loading.

  14. Comparison of in vitro methods and the in vivo metabolism of lindane for assessing the effects of repeated administration of ethanol on hepatic drug metabolism.

    PubMed

    Trela, B A; Carlson, G P; Chadwick, R W; Copeland, M F

    1985-12-01

    In vitro methods of assessing alterations in drug metabolism and the measurement of lindane metabolites in urine were compared for their ability to determine the influence of ethanol on drug metabolism. Ethanol was administered intraperitoneally (i.p.) to young adult female rats daily for 7 days at doses of 0.12, 0.60 and 3.0 ml/kg. No alterations were observed in ethylmorphine demethylation, hexobarbital oxidation or glucuronyltransferase. Aniline hydroxylation was decreased at the high dose level and aldrin epoxidation was increased at the intermediate dose. In vivo only the high dose of ethanol produced significant changes with significant increases observed for the oxidation of lindane to alcohol metabolites, the glucuronidation of the alcohol but not the chlorophenol metabolites, and glutathione conjugation. The latter increase was also observed in vitro. The in vivo and in vitro data suggest a minimal effect of ethanol on drug metabolism at low levels of administration. PMID:2418543

  15. Assessing T cell clonal size distribution: a non-parametric approach.

    PubMed

    Bolkhovskaya, Olesya V; Zorin, Daniil Yu; Ivanchenko, Mikhail V

    2014-01-01

    Clonal structure of the human peripheral T-cell repertoire is shaped by a number of homeostatic mechanisms, including antigen presentation, cytokine and cell regulation. Its accurate tuning leads to a remarkable ability to combat pathogens in all their variety, while systemic failures may lead to severe consequences like autoimmune diseases. Here we develop and make use of a non-parametric statistical approach to assess T cell clonal size distributions from recent next generation sequencing data. For 41 healthy individuals and a patient with ankylosing spondylitis, who undergone treatment, we invariably find power law scaling over several decades and for the first time calculate quantitatively meaningful values of decay exponent. It has proved to be much the same among healthy donors, significantly different for an autoimmune patient before the therapy, and converging towards a typical value afterwards. We discuss implications of the findings for theoretical understanding and mathematical modeling of adaptive immunity. PMID:25275470

  16. Distribution and assessment of marine debris in the deep Tyrrhenian Sea (NW Mediterranean Sea, Italy).

    PubMed

    Angiolillo, Michela; di Lorenzo, Bianca; Farcomeni, Alessio; Bo, Marzia; Bavestrello, Giorgio; Santangelo, Giovanni; Cau, Angelo; Mastascusa, Vincenza; Cau, Alessandro; Sacco, Flavio; Canese, Simonepietro

    2015-03-15

    Marine debris is a recognized global ecological concern. Little is known about the extent of the problem in the Mediterranean Sea regarding litter distribution and its influence on deep rocky habitats. A quantitative assessment of debris present in the deep seafloor (30-300 m depth) was carried out in 26 areas off the coast of three Italian regions in the Tyrrhenian Sea, using a Remotely Operated Vehicle (ROV). The dominant type of debris (89%) was represented by fishing gears, mainly lines, while plastic objects were recorded only occasionally. Abundant quantities of gears were found on rocky banks in Sicily and Campania (0.09-0.12 debris m(-2)), proving intense fishing activity. Fifty-four percent of the recorded debris directly impacted benthic organisms, primarily gorgonians, followed by black corals and sponges. This work provides a first insight on the impact of marine debris in Mediterranean deep ecosystems and a valuable baseline for future comparisons. PMID:25604749

  17. Assessing the occurrence and distribution of pyrethroids in water and suspended sediments

    USGS Publications Warehouse

    Hladik, M.L.; Kuivila, K.M.

    2009-01-01

    The distribution of pyrethroid insecticides in the environment was assessed by separately measuring concentrations in the dissolved and suspended sediment phases of surface water samples. Filtered water was extracted by HLB solid-phase extraction cartridges, while the sediment on the filter was sonicated and cleaned up using carbon and aluminum cartridges. Detection limits for the 13 pyrethroids analyzed by gas chromatography-tandem mass spectrometry were 0.5 to 1 ng L-1 for water and 2 to 6 ng g for the suspended sediments. Seven pyrethroids were detected in six water samples collected from either urban or agricultural creeks, with bifenthrin detected the most frequently and at the highest concentrations. In spiked water samples and field samples, the majority of the pyrethroids were associated with the suspended sediments.

  18. Assessment of trace metal distribution and contamination in surface soils of Hong Kong.

    PubMed

    Chen, T B; Wong, J W; Zhou, H Y; Wong, M H

    1997-01-01

    An intensive investigation was conducted to study the distribution of trace metals in surface soils of Hong Kong and to assess the soil environmental quality. From results of cluster analysis, and comparisons among soil types and areas, it is clearly shown that increases in trace metal concentrations in the soils were generally extensive and obvious in urban and orchard soils, less so in vegetable soils, whilst rural and forest soils were subjected to the least impact of anthropogenic sources of trace metals. However, some of the forest soils also contained elevated levels of As, Cu, and Pb. Urban soils in Hong Kong were heavily polluted by Pb from gasoline combustion. Agricultural soils, both orchard and vegetable soils, usually accumulated As, Cd, Cu, and Zn originating from applications of pesticides, animal manures, and fertilizers. In general, trace metal pollution in soils of the industrial areas and Pb pollution in the soils of the commercial and residential areas were obvious. PMID:15093432

  19. Importance of cyberspace for the assessment of the drug abuse market: preliminary results from the Psychonaut 2002 project.

    PubMed

    Schifano, Fabrizio; Leoni, Mauro; Martinotti, Giovanni; Rawaf, Salman; Rovetto, Francesco

    2003-08-01

    What do therapy and cybertherapy need to take into account to be effective for the treatment of drug-related disorders? The Psychonaut 2002 project is aimed to create a new and updated Web-based tool, which will be based on evolving drug scenarios, in order to provide professionals from the drug addiction field with easily accessible and reliable information. The drug abuse settings available on the Web will be described and the methodology will be discussed. Preliminary results of a search on MDMA and MDMA-like substances confirm that it is possible both to identify emerging trends and to provide information for prevention and appropriate intervention. PMID:14511453

  20. Anthelmintic drug residues in beef: UPLC-MS/MS method validation, European retail beef survey, and associated exposure and risk assessments.

    PubMed

    Cooper, K M; Whelan, M; Kennedy, D G; Trigueros, G; Cannavan, A; Boon, P E; Wapperom, D; Danaher, M

    2012-01-01

    Anthelmintic drugs are widely used to control parasitic infections in cattle. The ProSafeBeef project addressed the need for data on the exposure of European consumers of beef to potentially harmful drug residues. A novel analytical method based on matrix solid-phase dispersive extraction and ultra-performance liquid chromatography-tandem mass spectrometry was validated for 37 anthelmintic drugs and metabolites in muscle (assay decision limits, CC?,?=?0.15-10.2?µg?kg?¹). Seven European countries (France, Spain, Slovenia, Ireland, Italy, Belgium and Portugal) participated in a survey of retail beef purchased in local shops. Of 1061 beef samples analysed, 26 (2.45%) contained detectable residues of anthelmintic drugs (0.2-171?µg?kg?¹), none above its European Union maximum residue limit (MRL) or action level. Residues detected included closantel, levamisole, doramectin, eprinomectin, moxidectin, ivermectin, albendazole and rafoxanide. In a risk assessment applied to mean residue concentrations across all samples, observed residues accounted for less than 0.1% of the MRL for each compound. An exposure assessment based on the consumption of meat at the 99th percentile of consumption of adults in 14 European countries demonstrated that beef accounted for less than 0.02% of the acceptable daily intake for each compound in each country. This study is the first of its kind to apply such a risk-based approach to an extensive multi-residue survey of veterinary drug residues in food. It has demonstrated that the risk of exposure of the European consumer to anthelmintic drug residues in beef is negligible, indicating that regulation and monitoring is having the desired effect of limiting residues to non-hazardous concentrations. PMID:22360146

  1. Toward a unified model of passive drug permeation II: the physiochemical determinants of unbound tissue distribution with applications to the design of hepatoselective glucokinase activators.

    PubMed

    Ghosh, Avijit; Maurer, Tristan S; Litchfield, John; Varma, Manthema V; Rotter, Charles; Scialis, Renato; Feng, Bo; Tu, Meihua; Guimaraes, Cris R W; Scott, Dennis O

    2014-10-01

    In this work, we leverage a mathematical model of the underlying physiochemical properties of tissues and physicochemical properties of molecules to support the development of hepatoselective glucokinase activators. Passive distribution is modeled via a Fick-Nernst-Planck approach, using in vitro experimental data to estimate the permeability of both ionized and neutral species. The model accounts for pH and electrochemical potential across cellular membranes, ionization according to Henderson-Hasselbalch, passive permeation of the neutral species using Fick's law, and passive permeation of the ionized species using the Nernst-Planck equation. The mathematical model of the physiochemical system allows derivation of a single set of parameters governing the distribution of drug molecules across multiple conditions both in vitro and in vivo. A case study using this approach in the development of hepatoselective glucokinase activators via organic anion-transporting polypeptide-mediated hepatic uptake and impaired passive distribution to the pancreas is described. The results for these molecules indicate the permeability penalty of the ionized form is offset by its relative abundance, leading to passive pancreatic exclusion according to the Nernst-Planck extension of Fickian passive permeation. Generally, this model serves as a useful construct for drug discovery scientists to understand subcellular exposure of acids or bases using specific physiochemical properties. PMID:25024402

  2. ‘Oorja’ in India: Assessing a large-scale commercial distribution of advanced biomass stoves to households

    PubMed Central

    Thurber, Mark C.; Phadke, Himani; Nagavarapu, Sriniketh; Shrimali, Gireesh; Zerriffi, Hisham

    2015-01-01

    Replacing traditional stoves with advanced alternatives that burn more cleanly has the potential to ameliorate major health problems associated with indoor air pollution in developing countries. With a few exceptions, large government and charitable programs to distribute advanced stoves have not had the desired impact. Commercially-based distributions that seek cost recovery and even profits might plausibly do better, both because they encourage distributors to supply and promote products that people want and because they are based around properly-incentivized supply chains that could more be scalable, sustainable, and replicable. The sale in India of over 400,000 “Oorja” stoves to households from 2006 onwards represents the largest commercially-based distribution of a gasification-type advanced biomass stove. BP's Emerging Consumer Markets (ECM) division and then successor company First Energy sold this stove and the pelletized biomass fuel on which it operates. We assess the success of this effort and the role its commercial aspect played in outcomes using a survey of 998 households in areas of Maharashtra and Karnataka where the stove was sold as well as detailed interviews with BP and First Energy staff. Statistical models based on this data indicate that Oorja purchase rates were significantly influenced by the intensity of Oorja marketing in a region as well as by pre-existing stove mix among households. The highest rate of adoption came from LPG-using households for which Oorja's pelletized biomass fuel reduced costs. Smoke- and health-related messages from Oorja marketing did not significantly influence the purchase decision, although they did appear to affect household perceptions about smoke. By the time of our survey, only 9% of households that purchased Oorja were still using the stove, the result in large part of difficulties First Energy encountered in developing a viable supply chain around low-cost procurement of “agricultural waste” to make pellets. The business orientation of First Energy allowed the company to pivot rapidly to commercial customers when the household market encountered difficulties. The business background of managers also facilitated the initial marketing and distribution efforts that allowed the stove distribution to reach scale. PMID:25814822

  3. An inexpensive active optical remote sensing instrument for assessing aerosol distributions.

    PubMed

    Barnes, John E; Sharma, Nimmi C P

    2012-02-01

    Air quality studies on a broad variety of topics from health impacts to source/sink analyses, require information on the distributions of atmospheric aerosols over both altitude and time. An inexpensive, simple to implement, ground-based optical remote sensing technique has been developed to assess aerosol distributions. The technique, called CLidar (Charge Coupled Device Camera Light Detection and Ranging), provides aerosol altitude profiles over time. In the CLidar technique a relatively low-power laser transmits light vertically into the atmosphere. The transmitted laser light scatters off of air molecules, clouds, and aerosols. The entire beam from ground to zenith is imaged using a CCD camera and wide-angle (100 degree) optics which are a few hundred meters from the laser. The CLidar technique is optimized for low altitude (boundary layer and lower troposphere) measurements where most aerosols are found and where many other profiling techniques face difficulties. Currently the technique is limited to nighttime measurements. Using the CLidar technique aerosols may be mapped over both altitude and time. The instrumentation required is portable and can easily be moved to locations of interest (e.g. downwind from factories or power plants, near highways). This paper describes the CLidar technique, implementation and data analysis and offers specifics for users wishing to apply the technique for aerosol profiles. PMID:22442935

  4. Aromatic amine contents, component distributions and risk assessment in sludge from 10 textile-dyeing plants.

    PubMed

    Ning, Xun-An; Liang, Jie-Ying; Li, Rui-Jing; Hong, Zhen; Wang, Yu-Jie; Chang, Ken-Lin; Zhang, Ya-Ping; Yang, Zuo-Yi

    2015-09-01

    Aromatic amines (AAs), which are components of synthetic dyes, are recalcitrant to the wastewater treatment process and can accumulate in sludge produced by textile-dyeing, which may pose a threat to the environment. A comprehensive investigation of 10 textile-dyeing plants was undertaken in Guangdong Province in China. The contents and component distributions of AAs were evaluated in this study, and a risk assessment was performed. The total concentrations of 14 AAs (?14 AAs) varied from 11 ?g g(-1)dw to 82.5 ?g g(-1)dw, with a mean value of 25 ?g g(-1)dw. The component distributions of AAs were characterized by monocyclic anilines, of which 2-methoxy-5-methylaniline and 5-nitro-o-toluidine were the most dominant components. The risk quotient (RQ) value was used to numerically evaluate the ecological risk of 14 AAs in the environment. The result showed that the 14 AAs contents in textile-dyeing sludge may pose a high risk to the soil ecosystem after being discarded on soil or in a landfill. PMID:25973862

  5. Distribution, sources and health risk assessment of mercury in kindergarten dust

    NASA Astrophysics Data System (ADS)

    Sun, Guangyi; Li, Zhonggen; Bi, Xiangyang; Chen, Yupeng; Lu, Shuangfang; Yuan, Xin

    2013-07-01

    Mercury (Hg) contamination in urban area is a hot issue in environmental research. In this study, the distribution, sources and health risk of Hg in dust from 69 kindergartens in Wuhan, China, were investigated. In comparison with most other cities, the concentrations of total mercury (THg) and methylmercury (MeHg) were significantly elevated, ranging from 0.15 to 10.59 mg kg-1 and from 0.64 to 3.88 ?g kg-1, respectively. Among the five different urban areas, the educational area had the highest concentrations of THg and MeHg. The GIS mapping was used to identify the hot-spot areas and assess the potential pollution sources of Hg. The emissions of coal-power plants and coking plants were the main sources of THg in the dust, whereas the contributions of municipal solid waste (MSW) landfills and iron and steel smelting related industries were not significant. However, the emission of MSW landfills was considered to be an important source of MeHg in the studied area. The result of health risk assessment indicated that there was a high adverse health effect of the kindergarten dust in terms of Hg contamination on the children living in the educational area (Hazard index (HI) = 6.89).

  6. [Temporal distribution, sources, and risk assessment of polycyclic aromatic hydrocarbons in sediment core from Miyun reservoir].

    PubMed

    Guo, Jian-yang; Liao, Hai-qing; Han, Mei; Li, Wen; Zhang, Run-yu; Wang, Jing; Wu, Feng-chang

    2010-03-01

    The temporal distribution of polycyclic aromatic hydrocarbons (PAHs) was measured in sediment core from Miyun reservoir, and the possible sources and the potential risk assessment also have been identified. The aim of the present work is to understand the temporal trend of PAHs in Miyun reservoir recently. The concentrations of sigma PAH16 in sediment ranged from 618.5 ng/g to 1087.9 ng/g, and roughly, increased continuously from the bottom (16 cm under the surface) to the surface sediment. The PAHs in sediment core were mainly composed of phenanthrene and fluorene. The concentrations of phenanthrene and fluorene in sediment core were 236.1-417.9 ng/g and 91-130.8 ng/g, respectively. Both of them accounted for 47.2%-58.1% of the sigma PAH16 in sediments. Nevertheless, high-rings aromatic hydrocarbons (5-6 rings) were increased steadily in recent years. PAHs compositional profile indicated that the main source of PAHs was originated from the combustion of coal and biomass. However, the vertical profiles of Flu/Flu + Pyr and INP/INP + BghiP ratios suggested that the vehicles emission was increased very recently. Risk assessment suggested that PAHs in sediment from Miyun reservoir was no significant biological impairment, and low toxicological risk of PAHs was found up to now. PMID:20358818

  7. A Reverse Taxonomic Approach to Assess Macrofaunal Distribution Patterns in Abyssal Pacific Polymetallic Nodule Fields

    PubMed Central

    Janssen, Annika; Kaiser, Stefanie; Meißner, Karin; Brenke, Nils; Menot, Lenaick; Martínez Arbizu, Pedro

    2015-01-01

    Heightened interest in the exploitation of deep seafloor minerals is raising questions on the consequences for the resident fauna. Assessing species ranges and determination of processes underlying current species distributions are prerequisites to conservation planning and predicting faunal responses to changing environmental conditions. The abyssal central Pacific nodule belt, located between the Clarion and Clipperton Fracture Zones (CCZ), is an area prospected for mining of polymetallic nodules. We examined variations in genetic diversity and broad-scale connectivity of isopods and polychaetes across the CCZ. Faunal assemblages were studied from two mining claims (the eastern German and French license areas) located 1300 km apart and influenced by different productivity regimes. Using a reverse taxonomy approach based on DNA barcoding, we tested to what extent distance and large-scale changes in environmental parameters lead to differentiation in two macrofaunal taxa exhibiting different functions and life-history patterns. A fragment of the mitochondrial gene Cytochrome Oxidase Subunit 1 (COI) was analyzed. At a 97% threshold the molecular operational taxonomic units (MOTUs) corresponded well to morphological species. Molecular analyses indicated high local and regional diversity mostly because of large numbers of singletons in the samples. Consequently, variation in composition of genotypic clusters between sites was exceedingly large partly due to paucity of deep-sea sampling and faunal patchiness. A higher proportion of wide-ranging species in polychaetes was contrasted with mostly restricted distributions in isopods. Remarkably, several cryptic lineages appeared to be sympatric and occurred in taxa with putatively good dispersal abilities, whereas some brooding lineages revealed broad distributions across the CCZ. Geographic distance could explain variation in faunal connectivity between regions and sites to some extent, while assumed dispersal capabilities were not as important. PMID:25671322

  8. Distribution and risk assessment of 82 pesticides in Jiulong River and estuary in South China.

    PubMed

    Zheng, Senllin; Chen, Bin; Qiu, Xiaoyan; Chen, Meng; Ma, Zhiyuan; Yu, Xingguang

    2016-02-01

    To discover the distribution and risk of pesticides in Jiulong River and estuary, the residues of 102 pesticides were analyzed in water, sediment and clam samples collected from 35 sites in different seasons. A total number of 82 pesticides were detected and the occurrence and the risk to human and fish were assessed. Most of pesticides with high frequency were medium or low toxic except for DDTs. DDTs were the significant contaminant and the widely used dicofol was the new source of DDTs. The spatial and seasonal variation of pesticide distribution was linked with the distribution of orchards and farmlands. Health risk from river water consumption was low (RQ < 0.1) while that from clam consumption was medium (RQ = 0.84). Pesticides in water posed great risk to fish and among the 76 water samples analyzed, 65 of them showed high risk (RQ > 1) and 6 showed medium risk (0.1 ? QR < 1). The single chemical posed high risk to fish included DDTs, triazophos, fenvalerate, bifenthrin and cyfluthrin, and those showed medium risk included dicofol, butachlor, isocarbophos, terbufos and cyhalothrin. There were 14 single pesticides detected with concentration above 100 ng L(-1) in this study and the pesticide with the highest concentration was procymidone (3904 ng L(-1)). Further experiments illustrated that procymidone could disrupt the expression of vitellogenin in the estuarine fish even at environmental concentrations. DDTs, dicofol, triazophos, isocarbophos, terbufos, cyfluthrin, bifenthrin, fenvalerate, cyhalothrin, butachlor and procymidone have become the significant pesticides and should be considered in aquatic ecosystem risk management. PMID:26461443

  9. Ecological Niche Modelling using satellite data for assessing distribution of threatened species Ceropegia bulbosa Roxb.

    NASA Astrophysics Data System (ADS)

    Kumar, S.; Kulloli, R. N.; Tewari, J. C.; Singh, J. P.; Singh, A.

    2014-11-01

    Ceropegia bulbosa Roxb. is a narrow endemic, tuberous twiner of Asclepiadaceae family. It is medicinally important: tubers are nutritive and edible, leaves are digestive and a cure for dysentery and diarrhea. Exploitation for its tubers and poor regeneration of this species has shrunk its distribution. In order to know its present status, we report here the results of its appraisal in Rajasthan, using remote sensing and ground truthing in the past five years (2009-14). A base map of C. bulbosa was prepared using Geographical Information System (GIS), open source software Quantum GIS, SAGA. The Landsat Enhanced Thematic Mapper (ETM) +Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER), Global Digital Elevation Model (GDEM) Satellite Data were used in this study. ASTER and GDEM Data was clipped with district boundary and provided color range to get elevation information. A digital elevation model of Rajasthan physiography was developed from ASTER GDEM of 30-m resolution. GIS layers of Area of occurrences for C. bulbosa plant and elevation were created. This map along with topographic sheets of 1:50000 were used for field traversing and ground truthing as per GPS location inferred from map. Its geographic distribution was assessed using MaxEnt distribution modelling algorithm that employed 12 presence locality data, 19 bioclimatic variables, and elevation data. Results of this modelling predicted occurrence of C. bulbosa in the districts of Sirohi, Jalore, Barmer, Pali, Ajmer, Jhalawar, Dungarpur, Banswara, Baran, Kota, Bundi and Chittorgarh. Ground validation in these districts revealed its presence only at four places in three districts confirming its rarity. Analysis of dominance at their sites of occurrence revealed their poor populations and sub dominant status (RIV = 20-32) and very low density (2-12 plants per tenth ha).

  10. Independent Orbiter Assessment (IOA): Analysis of the electrical power distribution and control subsystem, volume 1

    NASA Technical Reports Server (NTRS)

    Schmeckpeper, K. R.

    1987-01-01

    The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. This report documents the independent analysis results corresponding to the Orbiter Electrical Power Distribution and Control (EPD and C) hardware. The EPD and C hardware performs the functions of distributing, sensing, and controlling 28 volt DC power and of inverting, distributing, sensing, and controlling 117 volt 400 Hz AC power to all Orbiter subsystems from the three fuel cells in the Electrical Power Generation (EPG) subsystem. Each level of hardware was evaluated and analyzed for possible failure modes and effects. Criticality was assigned based upon the severity of the effect for each failure mode. Of the 1671 failure modes analyzed, 9 single failures were determined to result in loss of crew or vehicle. Three single failures unique to intact abort were determined to result in possible loss of the crew or vehicle. A possible loss of mission could result if any of 136 single failures occurred. Six of the criticality 1/1 failures are in two rotary and two pushbutton switches that control External Tank and Solid Rocket Booster separation. The other 6 criticality 1/1 failures are fuses, one each per Aft Power Control Assembly (APCA) 4, 5, and 6 and one each per Forward Power Control Assembly (FPCA) 1, 2, and 3, that supply power to certain Main Propulsion System (MPS) valves and Forward Reaction Control System (RCS) circuits.

  11. Neurodevelopmental and Psychological Assessment of Adolescents Born to Drug-Addicted Parents: Effects of SES and Adoption

    ERIC Educational Resources Information Center

    Ornoy, Asher; Daka, Lulu; Goldzweig, Gil; Gil, Yoni; Mjen, Ludmila; Levit, Shabtai; Shufman, Emi; Bar-Hamburger, Rachel; Greenbaum, Charles W.

    2010-01-01

    Objectives: Prenatal exposure to heroin may have long-term consequences for development during early and middle childhood. The present research studied the cognitive, social, and emotional functioning of adolescents exposed to drugs prenatally, and investigated the extent to which the early adoption of children exposed prenatally to drugs would…

  12. [Environmental Hazards Assessment Program annual report, June 1992--June 1993]. Use of diatom distributions to monitor environmental health

    SciTech Connect

    Levine, R.H.

    1993-12-01

    A variety of approaches has been used in the past to assess the environmental impact of anthropogenic contaminants. One reliable index for aquatic environments is the analysis of diatom species distribution; the focus in this case being on the Savannah River. The completed objectives of this study were: (A) the development and use of procedures for measuring diatom distribution in the water column and (B) the development and evaluation of sediment sampling methods for retrospective analysis.

  13. Optimal sampling theory and population modelling - Application to determination of the influence of the microgravity environment on drug distribution and elimination

    NASA Technical Reports Server (NTRS)

    Drusano, George L.

    1991-01-01

    The optimal sampling theory is evaluated in applications to studies related to the distribution and elimination of several drugs (including ceftazidime, piperacillin, and ciprofloxacin), using the SAMPLE module of the ADAPT II package of programs developed by D'Argenio and Schumitzky (1979, 1988) and comparing the pharmacokinetic parameter values with results obtained by traditional ten-sample design. The impact of the use of optimal sampling was demonstrated in conjunction with NONMEM (Sheiner et al., 1977) approach, in which the population is taken as the unit of analysis, allowing even fragmentary patient data sets to contribute to population parameter estimates. It is shown that this technique is applicable in both the single-dose and the multiple-dose environments. The ability to study real patients made it possible to show that there was a bimodal distribution in ciprofloxacin nonrenal clearance.

  14. The crystallinity of cellulose controls the physical distribution of sorbed water and the capacity to present water for chemical degradation of a solid drug.

    PubMed

    Höckerfelt, Mina Heidarian; Alderborn, Göran

    2014-12-30

    The purpose of the research was to investigate the effect of moisture content of cellulose on the degradation of a drug in binary mixtures with cellulose. Physical mixtures of acetylsalicylic acid and two forms of cellulose, either microcrystalline cellulose or low crystalline cellulose, in the proportion 1:1 were stored at 50°C at a series of relative humidities (0-90%) for up to 175 days. The degradation rate constant of the drug increased with increased cellulose moisture content in a bi-regional fashion, with a low and a high degradation rate region. The shift from region 1 to 2 occurred at higher moisture content for the low crystalline cellulose. The relationships between rate constant and the temperature of maximum endothermic value overlapped for the two celluloses. It is proposed that the amount of water available for degradation of a solid drug is controlled by the water presenting capacity of cellulose which is dependent of the mechanism of sorption of water in cellulose. The water sorption of water can for cellulose satisfactorily be described by a two-site residence model with cellulose crystallinity as the structural correlate to the distribution between the two residence sites. PMID:25455777

  15. The epidemiology of drug use among New York State high school students: Distribution, trends, and change in rates of use.

    PubMed

    Kandel, D; Single, E; Kessler, R C

    1976-01-01

    A two-wave panel survey was carried out on a representative sample of New York State public secondary school students in fall 1971 and spring 1972. The majority of adolsecents have drunk beer or wine (82 per cent) smoked cigarettes (72 per cent) or used hard liquor (65 per cent). Better than one third (35 per cent) report the use of one or more illegal drugs. The illicit drugs most frequently used are marijuana (29 per cent) and hashish (21 per cent). About one in eight adolescents have used pills such as amphetamines and barbiturates, and about one in 12 have tried LSD or other psychedelics. Four per cent have used cocaine and 3 per cent heroin. Use of illicit drugs tends to be experimental and sporadic rather than regular. By contrast, about one in four regularly use beer or wine or smoke cigarettes. Self-reported rates of use increase over the course of a school year, and there is considerable turnover with respect to which adolescents are users. The increased number of hard liquor and marijuana users through the high school years results predominantly from more stability among users, rather than increased conversion of nonusers to users over the teen years. PMID:1247136

  16. Assessing potential impacts associated with contamination events in water distribution systems : a sensitivity analysis.

    SciTech Connect

    Davis, M. J.; Janke, R.; Taxon, T. N.

    2010-11-01

    An understanding of the nature of the adverse effects that could be associated with contamination events in water distribution systems is necessary for carrying out vulnerability analyses and designing contamination warning systems. This study examines the adverse effects of contamination events using models for 12 actual water systems that serve populations ranging from about 104 to over 106 persons. The measure of adverse effects that we use is the number of people who are exposed to a contaminant above some dose level due to ingestion of contaminated tap water. For this study the number of such people defines the impact associated with an event. We consider a wide range of dose levels in order to accommodate a wide range of potential contaminants. For a particular contaminant, dose level can be related to a health effects level. For example, a dose level could correspond to the median lethal dose, i.e., the dose that would be fatal to 50% of the exposed population. Highly toxic contaminants may be associated with a particular response at a very low dose level, whereas contaminants with low toxicity may only be associated with the same response at a much higher dose level. This report focuses on the sensitivity of impacts to five factors that either define the nature of a contamination event or involve assumptions that are used in assessing exposure to the contaminant: (1) duration of contaminant injection, (2) time of contaminant injection, (3) quantity or mass of contaminant injected, (4) population distribution in the water distribution system, and (5) the ingestion pattern of the potentially exposed population. For each of these factors, the sensitivities of impacts to injection location and contaminant toxicity are also examined. For all the factors considered, sensitivity tends to increase with dose level (i.e., decreasing toxicity) of the contaminant, with considerable inter-network variability. With the exception of the population distribution (factor 4 above), sensitivity to the various factors tends to be highest at lower impact levels (e.g., impacts below the 80th percentile). Conversely, for the population distribution factor, sensitivity is lowest at the lower impact levels. For injection duration, impacts generally are higher for longer duration injections. Definite patterns are present in the sensitivity of impacts to injection time, but these vary substantially across the networks. As would be expected, impacts are larger for larger mass injections, but the sensitivity can vary dramatically depending on dose level and the network. Estimated impacts can be sensitive to assumptions about how population is distributed in a network, particularly at high impact levels and high dose levels, again with considerable variability across networks. Finally, impacts can be sensitive to assumptions about ingestion patterns in the potentially exposed population, with sensitivities varying across networks and tending to be highest for high dose levels. When considered in combination with the other factors (but not including the ingestion model used), impacts at low dose levels (levels at which the effects of highly toxic contaminants can be significant) are most sensitive to injection duration. Similarly, when considered in combination, impacts at higher dose levels (levels required for significant effects from contaminants with low toxicity) are most sensitive to injection mass. At low dose levels, for a likely range in injection masses, impacts are not particularly sensitive to injection mass. The influence of the various factors on the location of high percentile injection locations can be as important or more important than their influence on the magnitudes of impacts. In addition, the choice of contaminant has a major influence on which nodes are high impact injection locations. The sharing (overlap) of the same high-percentile injection nodes for different values of a factor can vary substantially by contaminant and impact level (percentile of impact). Overlap tends to decrease with decreasing toxicity of the con

  17. Ovariectomized rats' femur treated with fibrates and statins. Assessment of pore-size distribution by 1H-NMR relaxometry.

    PubMed

    ?ipo?, Remus Sebastian; Fechete, Radu; Chelcea, Ramona Ioana; Moldovan, Dumitri?a; Pap, Zsuzsánna; Pávai, Zoltán; Demco, Dan Eugen

    2015-01-01

    The effects of two wonder drugs, simvastatins and fenofibrates on the proximal part of the femoris of a series of ovariectomized and non-ovariectomized Wistar albino rats was estimated qualitatively and semi-quantitatively by the modern method of 1D 1H-NMR T2-distribution. The 72 rats subjected to this study were divided in six groups and were sacrificed at two, four, six and eight weeks after ovariectomy and the proximal part of femoris was harvested. The CPMG (Carr-Purcell-Meiboom-Gill) echoes train curves were measured for the bones fully saturated with water during two months after two months of natural drying. These decays were analyzed by Laplace inversion and an average of normalized T2-distributions was considered for all rat's groups. The 1D averaged T2-distributions present four peaks, which were associated with protons in four major environments, from which the free water protons are used as spy molecules to explore the boundaries of cavities. In the approximation of spherical pores, the averaged T2-distributions were transformed in distributions of pores diameters. These were found in the range from 2 ?m up to 2 mm. The relative amplitudes, widths and position of deconvoluted distributions of small, medium and large cavities are used for a qualitatively analysis of the effect of our lipid-lowering drugs. For a semi-quantitatively analysis, we chose the diameter d of proximal part of femoris' trabecular cavities. We show that the positive or negative effects of treatments with simvastatins and fenofibrates are strongly dependent on the duration of treatment. Moreover, the treatment of healthy bone is generally counter-indicated. PMID:26429167

  18. Time-dependent Effects of Transcription- and Translation-halting Drugs on the Spatial Distributions of the E. coli Chromosome and Ribosomes

    PubMed Central

    Bakshi, Somenath; Choi, Heejun; Mondal, Jagannath; Weisshaar, James C.

    2014-01-01

    Summary Previously observed effects of rifampicin and chloramphenicol indicate that transcription and translation activity strongly affect the coarse spatial organization of the bacterial cytoplasm. Single-cell, time-resolved, quantitative imaging of chromosome and ribosome spatial distributions and ribosome diffusion in live E. coli provides insight into the underlying mechanisms. Monte Carlo simulations of model DNA-ribosome mixtures support a novel nucleoid-ribosome mixing hypothesis. In normal conditions, 70S-polysomes and the chromosomal DNA segregate, while 30S and 50S ribosomal subunits are able to penetrate the nucleoids. Growth conditions and drug treatments determine the partitioning of ribosomes into 70S-polysomes vs free 30S and 50S subunits. Entropic and excluded volume effects then dictate the resulting chromosome and ribosome spatial distributions. Direct observation of radial contraction of the nucleoids 0-5 min after treatment with either transcription- or translation-halting drugs supports the hypothesis that simultaneous transcription, translation, and insertion of proteins into the membrane (“transertion”) exerts an expanding force on the chromosomal DNA. Breaking of the DNA-RNA polymerase-mRNA-ribosome-membrane chain in either of two ways causes similar nucleoid contraction on a similar timescale. We suggest that chromosomal expansion due to transertion enables co-transcriptional translation throughout the nucleoids. PMID:25250841

  19. Preliminary assessment of the interaction of introduced biological agents with biofilms in water distribution systems.

    SciTech Connect

    Sinclair, Michael B.; Caldwell, Sara; Jones, Howland D. T.; Altman, Susan Jeanne; Souza, Caroline Ann; McGrath, Lucas K.

    2005-12-01

    Basic research is needed to better understand the potential risk of dangerous biological agents that are unintentionally or intentionally introduced into a water distribution system. We report on our capabilities to conduct such studies and our preliminary investigations. In 2004, the Biofilms Laboratory was initiated for the purpose of conducting applied research related to biofilms with a focus on application, application testing and system-scale research. Capabilities within the laboratory are the ability to grow biofilms formed from known bacteria or biofilms from drinking water. Biofilms can be grown quickly in drip-flow reactors or under conditions more analogous to drinking-water distribution systems in annular reactors. Biofilms can be assessed through standard microbiological techniques (i .e, aerobic plate counts) or with various visualization techniques including epifluorescent and confocal laser scanning microscopy and confocal fluorescence hyperspectral imaging with multivariate analysis. We have demonstrated the ability to grow reproducible Pseudomonas fluorescens biofilms in the annular reactor with plate counts on the order of 10{sup 5} and 10{sup 6} CFU/cm{sup 2}. Stationary phase growth is typically reached 5 to 10 days after inoculation. We have also conducted a series of pathogen-introduction experiments, where we have observed that both polystyrene microspheres and Bacillus cereus (as a surrogate for B. anthracis) stay incorporated in the biofilms for the duration of our experiments, which lasted as long as 36 days. These results indicated that biofilms may act as a safe harbor for bio-pathogens in drinking water systems, making it difficult to decontaminate the systems.

  20. Neutron Tomography Using Mobile Neutron Generators for Assessment of Void Distributions in Thermal Hydraulic Test Loops

    NASA Astrophysics Data System (ADS)

    Andersson, P.; Bjelkenstedt, T.; Sundén, E. Andersson; Sjöstrand, H.; Jacobsson-Svärd, S.

    Detailed knowledge of the lateral distribution of steam (void) and water in a nuclear fuel assembly is of great value for nuclear reactor operators and fuel manufacturers, with consequences for both reactor safety and economy of operation. Therefore, nuclear relevant two-phase flows are being studied at dedicated thermal-hydraulic test loop, using two-phase flow systems ranging from simplified geometries such as heated circular pipes to full scale mock-ups of nuclear fuel assemblies. Neutron tomography (NT) has been suggested for assessment of the lateral distribution of steam and water in such test loops, motivated by a good ability of neutrons to penetrate the metallic structures of metal pipes and nuclear fuel rod mock-ups, as compared to e.g. conventional X-rays, while the liquid water simultaneously gives comparatively good contrast. However, these stationary test loops require the measurement setup to be mobile, which is often not the case for NT setups. Here, it is acknowledged that fast neutrons of 14 MeV from mobile neutron generators constitute a viable option for a mobile NT system. We present details of the development of neutron tomography for this purpose at the division of Applied Nuclear Physics at Uppsala University. Our concept contains a portable neutron generator, exploiting the fusion reaction of deuterium and tritium, and a detector with plastic scintillator elements designed to achieveadequate spatial and energy resolution, all mounted in a light-weight frame without collimators or bulky moderation to allow for a mobile instrument that can be moved about the stationary thermal hydraulic test sections. The detector system stores event-to-event pulse-height information to allow for discrimination based on the energy deposition in the scintillator elements.