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Sample records for facilitate drug absorption

  1. A review of advanced oral drug delivery technologies facilitating the protection and absorption of protein and peptide molecules.

    Science.gov (United States)

    Choonara, Bibi F; Choonara, Yahya E; Kumar, Pradeep; Bijukumar, Divya; du Toit, Lisa C; Pillay, Viness

    2014-11-15

    The oral delivery of proteins and peptides is a dynamic research field despite the numerous challenges limiting their effective delivery. Successful oral delivery of proteins and peptides requires the accomplishment of three key tasks: protection of the macromolecules from degradation in the gastrointestinal tract (GIT), permeation through the intestinal barrier and absorption of molecules into the systemic circulation. Currently, no clinically useful oral formulations have been developed but several attempts have been made to overcome the challenges of low oral bioavailability resulting from poor absorption, poor permeation and enzymatic degradation of the proteins and peptides in the GIT. Present strategies attempt to provide structural protection of the proteins and peptides and improved absorption through the use of enzyme inhibitors, absorption enhancers, novel polymeric delivery systems and chemical modification. However, each of these technologies has their limitations despite showing positive results. This review attempts to discuss the physical and chemical barriers of the GIT with particular emphasis on the current approaches employed to overcome these barriers, including the evaluation of other non-parenteral routes of protein and peptide delivery. In addition, this review assimilates oral formulation strategies under development and within the clinical trial stage in relation to their benefits and drawbacks with regard to facilitating optimal protection and absorption of proteins and peptides, as well as pertinent future challenges and opportunities governing oral drug delivery. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Effect of oils on drug absorption

    OpenAIRE

    Palin, K.J.

    1981-01-01

    Oil and emulsion vehicles have been shown to alter the oral absorption of many drugs. This may be due to enhanced lymph flow and/or altered gastro-intestinal motility in the presence of the oils. The oral absorption of a model compound (DOT) in the presence of three chemically different oils, arachis oil, Miglyol 812 and liquid paraffin was investigated in rats, the influence of lymphatic absorption and gastro-intestinal motility being determined. The findings were applied to the for.mulation...

  3. Drug facilitated sexual assault with lethal outcome

    DEFF Research Database (Denmark)

    Mehling, Lena-Maria; Johansen, Sys Stybe; Wang, Xin

    2016-01-01

    A very serious case of DFSA (drug facilitated sexual assault) is presented, in which a six-year-old girl died following sedation with γ-hydroxybutyric acid (GHB). She had been sexually abused by a relative. Samples of cardiac blood, bile, vitreous humour, liver, kidney, brain tissues and hair were...

  4. Drug absorption from the irradiated rat small intestine in situ

    International Nuclear Information System (INIS)

    Venho, V.M.K.

    1976-01-01

    The absorption of acidic drugs phenobarbitone and sulphafurazole, basic drugs mecamylamine and quinidine, and a neutral drug isoniazid was studied in situ. Rats were irradiated 750 rad whole-body with 60 Co and the absorption experiment was done three and six days thereafter using the cannulated small intestine of urethane-anaesthetized rats. Drug disappearance from the intestinal lumen and drug levels in the whole blood and intestinal wall were measured. In control rats phenobarbitone showed the most rapid absorption and mecamylamine the slowest. Irradiation retarded the disappearance of all drugs from the intestinal lumen on the third postirradiation day. Fluid absorption was also diminished. On the sixth postirradiation day the absorption of phenobarbitone, sulphafurazole and mecamylamine had returned to the control level, but the absorption of quinidine and isoniazid was still retarded. After i.v. administration of drugs they were not significantly excreted into the intestinal contents and irradiation did not modify excretion. The distribution of drugs between the intestinal fluid and the intestinal wall was complete in the first 10 min of experiment. Mecamylamine and quinidine were lowered in the whole blood by irradiation. Blood levels of drugs did not correlate well to the rate of disappearance of drugs from the intestinal lumen. The reversible changes in absorption induced by irradiation are probably secondary effects of irradiation on intestinal morphology, permeability and transport capacity, composition, and possibly blood flow. (orig.) [de

  5. Systematic review: Helicobacter pylori infection and impaired drug absorption.

    Science.gov (United States)

    Lahner, E; Annibale, B; Delle Fave, G

    2009-02-15

    Impaired acid secretion may affect drug absorption and may be consequent to corporal Helicobacter pylori-gastritis, which may affect the absorption of orally administered drugs. To focus on the evidence of impaired drug absorption associated with H. pylori infection. Data sources were the systematic search of MEDLINE/EMBASE/SCOPUS databases (1980-April 2008) for English articles using the keywords: drug malabsorption/absorption, stomach, Helicobacter pylori, gastritis, gastric acid, gastric pH, hypochlorhydria, gastric hypoacidity. Study selection was made from 2099 retrieved articles, five studies were identified. Data were extracted from selected papers, investigated drugs, study type, main features of subjects, study design, intervention type and results were extracted. In all, five studies investigated impaired absorption of l-dopa, thyroxine and delavirdine in H. pylori infection. Eradication treatment led to 21-54% increase in l-dopa in Parkinson's disease. Thyroxine requirement was higher in hypochlorhydric goitre with H. pylori-gastritis and thyrotropin levels decreased by 94% after treatment. In H. pylori- and HIV-positive hypochlorhydric subjects, delavirdine absorption increased by 57% with orange juice administration and by 150% after eradication. A plausible mechanism of impaired drug absorption is decreased acid secretion in H. pylori-gastritis patients. Helicobacter pylori infection and hypochlorhydria should be considered in prescribing drugs the absorption of which is potentially affected by intragastric pH.

  6. Advancement in integrin facilitated drug delivery.

    Science.gov (United States)

    Arosio, Daniela; Casagrande, Cesare

    2016-02-01

    The research of integrin-targeted anticancer agents has recorded important advancements in ingenious design of delivery systems, based either on the prodrug approach, or on nanoparticle carriers, but for now, none of these has reached a clinical stage of development. Past work in this area has been extensively reviewed by us and others. Thus, the purpose and scope of the present review is to survey the advancement reported in the last 3years, with focus on innovative delivery systems that appear to afford openings for future developments. These systems exploit the labelling with conventional and novel integrin ligands for targeting the interface of cancer cells and of endothelial cells involved in cancer angiogenesis, with the proteins of the extracellular matrix, in the circulation, in tissues, and in tumour stroma, as the site of progression and metastatic evolution of the disease. Furthermore, these systems implement the expertise in the development of nanomedicines to the purpose of achieving preferential biodistribution and uptake in cancer tissues, internalisation in cancer cells, and release of the transported drugs at intracellular sites. The assessment of the value of controlling these factors, and their combination, for future developments requires support of biological testing in appropriate mechanistic models, but also imperatively demand confirmation in therapeutically relevant in vivo models for biodistribution, efficacy, and lack of off-target effects. Thus, among many studies, we have tried to point out the results supported by relevant in vivo studies, and we have emphasised in specific sections those addressing the medical needs of drug delivery to brain tumours, as well as the delivery of oligonucleotides modulating gene-dependent pathological mechanism. The latter could constitute the basis of a promising third branch in the therapeutic armamentarium against cancer, in addition to antibody-based agents and to cytotoxic agents. Copyright © 2015

  7. Facilitating Intracellular Drug Delivery by Ultrasound-Activated Microbubbles

    NARCIS (Netherlands)

    Lammertink, BHA

    2017-01-01

    The goal of this thesis was to investigate the combination of ultrasound and microbubbles (USMB) for intracellular delivery of (model) drugs in vitro. We have focused on clinically approved drugs, i.e. cisplatin, and microbubbles, i.e. SonoVue™, to facilitate clinical translation. In addition, model

  8. Quantitation of small intestinal permeability during normal human drug absorption

    OpenAIRE

    Levitt, David G

    2013-01-01

    Background Understanding the quantitative relationship between a drug?s physical chemical properties and its rate of intestinal absorption (QSAR) is critical for selecting candidate drugs. Because of limited experimental human small intestinal permeability data, approximate surrogates such as the fraction absorbed or Caco-2 permeability are used, both of which have limitations. Methods Given the blood concentration following an oral and intravenous dose, the time course of intestinal absorpti...

  9. Drug gastrointestinal absorption in rat: Strain and gender differences.

    Science.gov (United States)

    Oltra-Noguera, Davinia; Mangas-Sanjuan, Victor; González-Álvarez, Isabel; Colon-Useche, Sarin; González-Álvarez, Marta; Bermejo, Marival

    2015-10-12

    Predictive animal models of intestinal drug absorption are essential tools in drug development to identify compounds with promising biopharmaceutical properties. In situ perfusion absorption studies are routinely used in the preclinical setting to screen drug candidates. The objective of this work is to explore the differences in magnitude and variability on intestinal absorption associated with rat strain and gender. Metoprolol and Verapamil absorption rate coefficients were determined using the in situ closed loop perfusion model in four strains of rats and in both genders. Strains used were Sprague-Dawley, Wistar-Han, Wistar-Unilever, Long-Evans and CD∗IGS. In the case of Metoprolol only CD∗IGS and Wistar Unilever showed differences between males and females. For Verapamil, Wistar Han and Sprague-Dawley strains do not show differences between male and female rats. That means that in these strains permeability data from male and female could be combined. In male rats, which are commonly used for permeability estimation, there were differences for Metoprolol permeability between Sprague-Dawley (with lower permeability values) and the other strains, while for Verapamil Sprague-Dawley and Wistar-Han showed the lower permeability values. In conclusion, the selection of rat's strain and gender for intestinal absorption experiments is a relevant element during study design and data from different strains may not be always comparable. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Forensic toxicology in drug-facilitated sexual assault.

    Science.gov (United States)

    Dinis-Oliveira, Ricardo Jorge; Magalhães, Teresa

    2013-09-01

    The low rates of reporting, prosecution and conviction that characterize sexual assault, is likely even more evident in drug-facilitated cases. Typically, in these crimes, victims are incapacitated and left unable to resist sexual advances, unconscious, unable to fight off the abuser or to say "no" and unable to clearly remember the circumstances surrounding the events due to anterograde amnesia. The consequence is the delay in performing toxicological analysis aggravated by the reluctance of the victim to disclose the crime. Moreover since "date rape drugs" are often consumed with ethanol and exhibit similar toxicodynamic effects, the diagnosis is erroneously performed as being classical ethanol intoxication. Therefore, it is imperative to rapidly consider toxicological analysis in drug-facilitated sexual assaults. The major focus of this review is to harmonize practical approaches and guidelines to rapidly uncover drug-facilitated sexual assault, namely issues related to when to perform toxicological analysis, toxicological requests, samples to be collected, storage, preservation and transport precautions and xenobiotics or endobiotics to be analyzed.

  11. In Silico Modeling of Gastrointestinal Drug Absorption: Predictive Performance of Three Physiologically Based Absorption Models.

    Science.gov (United States)

    Sjögren, Erik; Thörn, Helena; Tannergren, Christer

    2016-06-06

    Gastrointestinal (GI) drug absorption is a complex process determined by formulation, physicochemical and biopharmaceutical factors, and GI physiology. Physiologically based in silico absorption models have emerged as a widely used and promising supplement to traditional in vitro assays and preclinical in vivo studies. However, there remains a lack of comparative studies between different models. The aim of this study was to explore the strengths and limitations of the in silico absorption models Simcyp 13.1, GastroPlus 8.0, and GI-Sim 4.1, with respect to their performance in predicting human intestinal drug absorption. This was achieved by adopting an a priori modeling approach and using well-defined input data for 12 drugs associated with incomplete GI absorption and related challenges in predicting the extent of absorption. This approach better mimics the real situation during formulation development where predictive in silico models would be beneficial. Plasma concentration-time profiles for 44 oral drug administrations were calculated by convolution of model-predicted absorption-time profiles and reported pharmacokinetic parameters. Model performance was evaluated by comparing the predicted plasma concentration-time profiles, Cmax, tmax, and exposure (AUC) with observations from clinical studies. The overall prediction accuracies for AUC, given as the absolute average fold error (AAFE) values, were 2.2, 1.6, and 1.3 for Simcyp, GastroPlus, and GI-Sim, respectively. The corresponding AAFE values for Cmax were 2.2, 1.6, and 1.3, respectively, and those for tmax were 1.7, 1.5, and 1.4, respectively. Simcyp was associated with underprediction of AUC and Cmax; the accuracy decreased with decreasing predicted fabs. A tendency for underprediction was also observed for GastroPlus, but there was no correlation with predicted fabs. There were no obvious trends for over- or underprediction for GI-Sim. The models performed similarly in capturing dependencies on dose and

  12. [Drug-facilitated crime and sexual abuse: a pediatric observation].

    Science.gov (United States)

    Rey-Salmon, C; Pépin, G

    2007-11-01

    Drug-facilitated crime in sexual assault situations remains insufficiently recognized by physicians. In the possible context of an assault and in front of recent neuropsychicological disturbances in a child, such an issue has to be considered. The quality of sampling, the use of ultra-sensitive and specific toxicologic methods and a clinical-biological collaboration allow to recognize this form of delinquency whose consequences are both medical and legal.

  13. A two-dimensional mathematical model of percutaneous drug absorption

    Directory of Open Access Journals (Sweden)

    Kubota K

    2004-06-01

    Full Text Available Abstract Background When a drug is applied on the skin surface, the concentration of the drug accumulated in the skin and the amount of the drug eliminated into the blood vessel depend on the value of a parameter, r. The values of r depend on the amount of diffusion and the normalized skin-capillary clearence. It is defined as the ratio of the steady-state drug concentration at the skin-capillary boundary to that at the skin-surface in one-dimensional models. The present paper studies the effect of the parameter values, when the region of contact of the skin with the drug, is a line segment on the skin surface. Methods Though a simple one-dimensional model is often useful to describe percutaneous drug absorption, it may be better represented by multi-dimensional models. A two-dimensional mathematical model is developed for percutaneous absorption of a drug, which may be used when the diffusion of the drug in the direction parallel to the skin surface must be examined, as well as in the direction into the skin, examined in one-dimensional models. This model consists of a linear second-order parabolic equation with appropriate initial conditions and boundary conditions. These boundary conditions are of Dirichlet type, Neumann type or Robin type. A finite-difference method which maintains second-order accuracy in space along the boundary, is developed to solve the parabolic equation. Extrapolation in time is applied to improve the accuracy in time. Solution of the parabolic equation gives the concentration of the drug in the skin at a given time. Results Simulation of the numerical methods described is carried out with various values of the parameter r. The illustrations are given in the form of figures. Conclusion Based on the values of r, conclusions are drawn about (1 the flow rate of the drug, (2 the flux and the cumulative amount of drug eliminated into the receptor cell, (3 the steady-state value of the flux, (4 the time to reach the steady

  14. PS-109 Barriers and facilitators to implementing drug changes caused by drug tenders and shortages

    DEFF Research Database (Denmark)

    Rishøj, Rikke Mie; Christrup, Lona Louring; Clemmensen, Marianne H

    2015-01-01

    . Purpose To identify barriers and facilitators for implementing drug changes due to drug tenders and shortages in Danish public hospitals. Material and methods Six focus group interviews were conducted at three hospitals in different regions of the country. At each hospital two focus group interviews were...... thematically through content analysis. Results Barriers Identified included: frequent changes of labelling, packages and drug names. Furthermore, implementing drug changes requires extra resources and finance. Technologies such as computerised physician order entry and barcode scanning systems were perceived...... as potential facilitators, but also as barriers in cases where the quality and implementation of the systems were not adequate. Facilitators included: hospital pharmacy services and lower drug prices. Furthermore recommendations on generic prescription, optimisation of the tendering process and support...

  15. Remote controlled capsules in human drug absorption (HDA) studies.

    Science.gov (United States)

    Wilding, Ian R; Prior, David V

    2003-01-01

    The biopharmaceutical complexity of today's new drug candidates provides significant challenges for pharmaceutical scientists in terms of both candidate selection and optimizing subsequent development strategy. In addition, life cycle management of marketed drugs has become an important income stream for pharmaceutical companies, but the selection of least risk/highest benefit strategies is far from simple. The proactive adoption of human drug absorption (HDA) studies using remote controlled capsules offers the pharmaceutical scientist significant guidance for planning a route through the maze of product development. This review examines the position of HDA studies in drug development, using a variety of case histories and an insightful update on remote controlled capsules to achieve site-specific delivery.

  16. Facilitation of transscleral drug delivery by drug loaded magnetic polymeric particles.

    Science.gov (United States)

    Mousavikhamene, Zeynab; Abdekhodaie, Mohammad J; Ahmadieh, Hamid

    2017-10-01

    A unique method was used to facilitate ocular drug delivery from periocular route by drug loaded magnetic sensitive particles. Injection of particles in periocular space along the eye axis followed by application of magnetic field in front of the eye would trigger the magnetic polymeric particles to move along the direction of magnetic force and reside against the outer surface of the sclera. This technique prevents removal of drug in the periocular space, observed in conventional transscleral drug delivery systems and hence higher amount of drug can enter the eye in a longer period of time. The experiments were performed by fresh human sclera and an experimental setup. Experimental setup was designed by side by side diffusion cell and hydrodynamic and thermal simulation of the posterior segment of the eye were applied. Magnetic polymeric particles were synthesized by alginate as a model polymer, iron oxide nanoparticles as a magnetic agent and diclofenac sodium as a model drug and characterized by SEM, TEM, DLS and FT-IR techniques. According to the SEM images, the size range of particles is around 60 to 800nm. The results revealed that the cumulative drug transfer from magnetic sensitive particles across the sclera improves by 70% in the presence of magnetic field. The results of this research show promising method of drug delivery to use magnetic properties to facilitate drug delivery to the back of the eye. Copyright © 2017. Published by Elsevier B.V.

  17. An adverse drug event manager facilitates spontaneous reporting of adverse drug reactions

    DEFF Research Database (Denmark)

    Vinther, Siri; Klarskov, Pia; Borgeskov, Hanne

    2017-01-01

    INTRODUCTION: Spontaneous reporting of adverse drug reactions (ADRs) is used for continuous risk-benefit evaluation of marketed pharmaceutical products and for signal detection. The Adverse Drug Event Manager (ADEM) is a service offered to clinicians employed at hospitals in the Capital Region......%). The drugs most frequently reported were lisdexamphetamine (n = 40), rivaroxaban (n = 16) and warfarin (n = 15) (vaccines excluded). In 13 out of 484 reports, the ADR was associated with a fatal outcome. CONCLUSION: The findings of this study indicate that an ADEM promotes and facilitates spontaneous ADR...

  18. Functionalization of nanodiamond with vitamin E TPGS to facilitate oral absorption of curcumin.

    Science.gov (United States)

    Cheng, Bingchao; Pan, Hao; Liu, Dandan; Li, Dongyang; Li, Jinyu; Yu, Shihui; Tan, Guoxin; Pan, Weisan

    2018-04-05

    The purpose of this work was to develop a d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) decorated nanodiamond (ND) system loading water-insoluble curcumin (ND/CUR/TPGS) to improve the colloidal dispersity and oral bioavailability of the preparation. CUR was physically loaded into ND clusters, then TPGS was coated to the ND/CUR complex forming amorphous nanostructure on the interparticle nanocage of the ND substrate. The formulation of the nanocomplexes was optimized using response surface methodology, and the optimal ND/CUR/TPGS showed small particle size (196.32 nm), high drug loading efficiency (81.59%) and core-shell structure. In vitro release study demonstrated that the nanocomplexes provided a sustained release behavior. The absorptive concentration of ND/CUR/TPGS was dramatically improved in total intestinal tract compared with CUR suspension, and the absorption was controlled by multiple transcytosis mechanisms. Furthermore, the pharmacokinetic studies demonstrated that ND/CUR/TPGS had significantly higher C max (4.50-fold), larger AUC 0-t (10.67-fold), and longer MRT 0-t (3.07-fold) in contrast with that of CUR suspension. Therefore, ND/CUR/TPGS presented great potential for oral delivery of insoluble and poorly permeable drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Solid dispersions in oncology: a solution to solubility-limited oral drug absorption

    NARCIS (Netherlands)

    Sawicki, Emilia

    2017-01-01

    This thesis discusses the formulation method solid dispersion and how it works to resolve solubility-limited absorption of orally dosed anticancer drugs. Dissolution in water is essential for drug absorption because only dissolved drug molecules are absorbed. The problem is that half of the arsenal

  20. Gastrointestinal drug absorption in rats exposed to 60Co γ-radiation

    International Nuclear Information System (INIS)

    Brady, M.E.

    1976-01-01

    Following exposure of the gastrointestinal (GI) tract to ionizing radiation, its structure and function are altered for several days. Such alterations may affect the bioavailability of orally administered drugs. The potential mechanisms by which radiation may affect drug absorption were explored by studying the absorption of four test drugs, sulfanilamide, bretylium, sulfisoxazole acetyl, and riboflavin, in rats that were exposed to 850 R cobalt-60 gamma-radiation or sham irradiated. In one series of experiments, the drugs were administered orally and the amount of drug excreted in urine was used as a measure of the extent of their absorption. Cumulative urinary excretion of the drugs was shown to be a valid measure of absorption since it was not affected by radiation after intravenous administration of the drugs. At one day post-irradiation, the extent of absorption of sulfanilamide and bretylium was not affected by radiation but the absorption of sulfisoxazole acetyl and riboflavin was increased. At five days post-irradiation, there was no detectable difference between irradiated and control animals in the extent of absorption of the drugs. The fraction of sulfanilamide excreted in the urine as 4 N-conjugate was increased at one day post-irradiation. The increased excretion of metabolite appeared to result from metabolism of the drug by gut flora prior to absorption. This study shows that radiation-induced alterations in the absorption of orally administered drugs are due primarily to slowed gastric emptying. In general, slowed gastric emptying causes the rate of drug absorption to decline. The extent of absorption of drugs that are normally well absorbed is not affected by radiation while the extent of absorption of drugs that normally are absorbed poorly may be increased after irradiation of the GI tract

  1. Interplay of Drug-Metabolizing Enzymes and Transporters in Drug Absorption and Disposition.

    Science.gov (United States)

    Shi, Shaojun; Li, Yunqiao

    2014-01-01

    In recent years, the functional interplay between drug-metabolizing enzymes (DMEs) and drug transporters (DTs) in drug absorption and disposition, as well as the complex drug interactions (DIs), has become an intriguing contention, which has also been termed the "transport-metabolism interplay". The current mechanistic understanding for this interplay is first discussed. In the present article, studies investigating the interplay between cytochrome P450 enzymes (CYPs) and efflux transporters have been systematically reviewed in vitro, in situ, in silico, in animals and humans, followed by CYPs-uptake transporters, CYPs-uptake transporters-efflux transporters, and phase II metabolic enzymes-transporters interplay studies. Although several cellular, isolated organ and whole animal studies, in conjunction with simulation and modelling, have addressed the issue that DMEs and DTs can work cooperatively to affect the bioavailability of shared substrate drugs, convincing evidences in human studies are still lacking. Furthermore, the functional interplay between DMEs and DTs will be highly substrate- and dose- dependent. Additionally, we review recent studies to evaluate the influence of genetic variations in the interplay between DMEs and DTs, which might be helpful for the prediction of pharmacokinetics (PK) and possible DIs in human more correctly. There is strong evidence of coordinately regulated DEMs and DTs gene expression and protein activity (e.g. nuclear receptors). Taken together, further investigations and analysis are urgently needed to explore the functional interplay of DMEs and DTs and to delineate the underlying mechanisms.

  2. Drug Facilitated Sexual Assault and That the Problems in Turkey

    Directory of Open Access Journals (Sweden)

    Nabi Kantarcı

    2012-10-01

    Full Text Available The assailants of sexuel assault to serve this purpose to the victims of many different drug can use. These drugs can be applied together with alcohol, soft drinks, water and other drinks can be given together. Most of these drugs tasteless and odorless. In a few minutes after ingestion chemical effect of drugs can start. Victims the conscious reduction and limitation of the physical move occur. Drug drinking from the pass the time until impact memory loss can occur. For this purpose the main benzodiazepines (Diazepam, flunitrazepam, lorazepam, etc., hypnotics (Zopiclone, zolpidem, anesthetics (Gama-hydroxybutyrate, ketamine, amphetamines (Metylendioxymetamphetamine=ecstasy, opiats (Cocaine, cannabis=marihuana and alcohols such as ethanol substances used. However in study frequently encountered in the literature; cocaine, cannabis, metylendioxymetamphetamine, zolpidem, ketamine hydrochloride, zopiclone, gamma hydroxybutirate, diazepam, flunitrazepam and the effects of these substances after oral ingestion were evaluated and the approach to victims.

  3. Radiological absorption characteristics of sedatives, hypnotic drugs and psychopharmaceuticals with respect to drug intoxications in suicides

    International Nuclear Information System (INIS)

    Melchert, H.

    1980-01-01

    When in cases of patients with severe intoxication aspiration is suspected clinically, an X-ray image of the thorax is made in order to prevent that atelectases or inflammatory pulmonary infiltrations remain undetected, in addition, an X-ray image of the abdomen should be made in each in which the swallowed preparation has not been identified, because our investigations have proved that any drugs of any kind with an absorption coefficient above 0.23 are radiologically detectable, when the resorption process is not finished yet. In shadow-producing pharmaceuticals these abdominal X-ray images allow not only the examination and supervision of the toxic resorption of an enterally taken preparation, but also the possible identification of the type the drug belongs to. Moreover, information about quantity, resorption, and localisation of the tablets being somewhere in the gastrointestinal tract can be obtained. (orig.) [de

  4. Fitness-compensatory mutations facilitate the spread of drug ...

    Indian Academy of Sciences (India)

    Charissa C. Naidoo

    2017-08-19

    Aug 19, 2017 ... Cells were seeded at 2×105 cells/mL in 24-well cell culture plates (Porvair). Infection ..... the intermediary metabolism and respiration group, and conserved hypotheticals ... cellular growth in F15/LAM4/KZN strains. Mycobacte- .... drugs and is thought to occur as a result of metabolic shut- down (Gomez and ...

  5. Effects of PEGylated lipid nanoparticles on the oral absorption of one BCS II drug: a mechanistic investigation

    Directory of Open Access Journals (Sweden)

    Zhang XW

    2014-11-01

    Full Text Available Xingwang Zhang,* Guijiang Chen,* Tianpeng Zhang, Zhiguo Ma, Baojian WuDivision of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, People’s Republic of China*These authors contributed equally to this workAbstract: Lipid nanocarriers are becoming a versatile platform for oral delivery of lipophilic drugs. In this article, we aimed to explore the gastrointestinal behaviors of lipid nanoparticles and the effect of PEGylation on oral absorption of fenofibrate (FN, a Biopharmaceutics Classification System (BCS II model drug. FN-loaded PEGylated lipid nanoparticles (FN-PLNs were prepared by the solvent-diffusion method and characterized by particle size distribution, morphology, Fourier transform infrared spectroscopy, and drug release. Lipolytic experiments were performed to assess the resistance of lipid nanoparticles against pancreatic lipase. Pharmacokinetics was evaluated in rats after oral administration of FN preparations. The obtained FN-PLNs were 186.7 nm in size with an entrapment efficiency of >95%. Compared to conventional lipid nanoparticles, PLNs exhibited slower drug release in the lipase-containing medium, strikingly reduced mucin binding, and suppressed lipolysis in vitro. Further, oral absorption of FN was significantly enhanced using PLNs with relative bioavailability of 123.9% and 157.0% to conventional lipid nanoparticles and a commercial formulation (Lipanthyl®, respectively. It was demonstrated that reduced mucin trapping, suppressed lipolysis, and/or improved mucosal permeability were responsible for increased oral absorption. These results facilitated a better understanding of the in vivo fate of lipid nanoparticles, and suggested the potential of PLNs as oral carriers of BCS II drugs.Keywords: fenofibrate, lipid nanoparticles, PEGylation, oral bioavailability, absorption mechanism

  6. Mapping Quantitatively Regional Drug Absorption in Canines with IntelliCap System

    NARCIS (Netherlands)

    Becker, D.; Schütz, H.; Beyerbach, A.; Zou, H.; Shimizu, J.; Iordanov, V.P.

    2011-01-01

    Quantitative regional absorption of a drug under development was studied by using the novel IntelliCap system. IntelliCap is an orally swallowable programmable drug delivery capsule and capable of real-time monitoring of physiological conditions (pH, temperature), consequently allowing localization

  7. Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells

    International Nuclear Information System (INIS)

    Artursson, P.; Karlsson, J.

    1991-01-01

    Monolayers of a well differentiated human intestinal epithelial cell line, Caco-2, were used as a model to study passive drug absorption across the intestinal epithelium. Absorption rate constants (expressed as apparent permeability coefficients) were determined for 20 drugs and peptides with different structural properties. The permeability coefficients ranged from approximately 5 x 10 - 8 to 5 x 10 - 5 cm/s. A good correlation was obtained between data on oral absorption in humans and the results in the Caco-2 model. Drugs that are completely absorbed in humans had permeability coefficients greater than 1 x 10 - 6 cm/s. Drugs that are absorbed to greater than 1% but less than 100% had permeability coefficients of 0.1-1.0 x 10 - 6 cm/s while drugs and peptides that are absorbed to less than 1% had permeability coefficients of less than or equal to 1 x 10 - 7 cm/s. The results indicate that Caco-2 monolayers can be used as a model for studies on intestinal drug absorption

  8. Terahertz absorption spectra of commonly used antimalarial drugs

    Science.gov (United States)

    Bawuah, Prince; Zeitler, J. Axel; Ketolainen, Jarkko; Peiponen, Kai-Erik

    2018-03-01

    Terahertz (THz) spectra from the pure forms [i.e. the active pharmaceutical ingredients (APIs)] of four commonly used antimalarial drugs are reported. The well-defined spectral fingerprints obtained for these APIs in the spectral range of 0.1 THz-3 THz show the sensitivity of the THz time-domain spectroscopic (THz-TDS) method for screening antimalarial drugs. For identification purpose, two commercially available antimalarial tablets were detected. Clear spectral fingerprints of the APIs in the antimalarial tablets were obtained even amidst the several types of excipients present in the tablets. This observation further proves the high sensitivity of the THz techniques in tracking the presence or absence of API in a pharmaceutical tablet. We envisage that the spectral data obtained for these drugs can contribute to a spectroscopic database in the far infrared spectral region and hence support the modelling of THz sensing to differentiate between genuine and counterfeit antimalarial tablets.

  9. Terahertz absorption spectra of commonly used antimalarial drugs

    Science.gov (United States)

    Bawuah, Prince; Zeitler, J. Axel; Ketolainen, Jarkko; Peiponen, Kai-Erik

    2018-06-01

    Terahertz (THz) spectra from the pure forms [i.e. the active pharmaceutical ingredients (APIs)] of four commonly used antimalarial drugs are reported. The well-defined spectral fingerprints obtained for these APIs in the spectral range of 0.1 THz-3 THz show the sensitivity of the THz time-domain spectroscopic (THz-TDS) method for screening antimalarial drugs. For identification purpose, two commercially available antimalarial tablets were detected. Clear spectral fingerprints of the APIs in the antimalarial tablets were obtained even amidst the several types of excipients present in the tablets. This observation further proves the high sensitivity of the THz techniques in tracking the presence or absence of API in a pharmaceutical tablet. We envisage that the spectral data obtained for these drugs can contribute to a spectroscopic database in the far infrared spectral region and hence support the modelling of THz sensing to differentiate between genuine and counterfeit antimalarial tablets.

  10. New Insights into Drug Absorption from Oil Depots

    NARCIS (Netherlands)

    Kalicharan, R.W.

    2017-01-01

    Sustained delivery formulations are used in order to prolong the pharmacological activity of a drug. A commonly used parenteral sustained delivery formulation is an oil depot which consists of a solution of lipophilic molecules in a vegetable oil. These are normally administered either

  11. Piracetam, an AMPAkine drug, facilitates memory consolidation in the day-old chick.

    Science.gov (United States)

    Samartgis, Jodi R; Schachte, Leslie; Hazi, Agnes; Crowe, Simon F

    2012-12-01

    Piracetam is an AMPAkine drug that may have a range of different mechanisms at the cellular level, and which has been shown to facilitate memory, amongst its other effects. This series of experiments demonstrated that a 10mg/kg dose of piracetam facilitated memory consolidation in the day-old chick when injected from immediately until 120min after weak training (i.e. using a 20% v/v concentration of methyl anthranilate) with the passive avoidance learning task. Administration of piracetam immediately after training led to memory facilitation which lasted for up to 24h following training. This dose of the AMPAkine was not shown to facilitate memory reconsolidation. These findings support the contention that application of the AMPAkine piracetam facilitates memory using a weak training task, and extend the range of actions previously noted with NMDA-related agents to those which also facilitate the AMPA receptor. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Early pharmaceutical profiling to predict oral drug absorption

    DEFF Research Database (Denmark)

    Bergström, Christel A S; Holm, René; Jørgensen, Søren Astrup

    2014-01-01

    Preformulation measurements are used to estimate the fraction absorbed in vivo for orally administered compounds and thereby allow an early evaluation of the need for enabling formulations. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary of the pharmac......Preformulation measurements are used to estimate the fraction absorbed in vivo for orally administered compounds and thereby allow an early evaluation of the need for enabling formulations. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary...... and state-of-the art methodologies to study API properties impacting on oral absorption are reviewed. Assays performed during early development, i.e. physicochemical characterization, dissolution profiles under physiological conditions, permeability assays and the impact of excipients on these properties...

  13. Development and Evaluation of Naproxen Sodium Gel Using Piper cubeba for Enhanced Transdermal Drug Delivery and Therapeutic Facilitation.

    Science.gov (United States)

    Patwardhan, Sunetra; Patil, Manohar; Sockalingam, Anbazhagan

    2017-01-01

    The absorption of drug through skin avoids many side effects of oral route like gastric irritation, nausea, systemic toxicity etc and thus improves patient compliance. Naproxen sodium (NPRS) is one of the potent NSAID agents. The present study was aimed to develop and evaluate the gel formulation containing NPRS for transdermal drug delivery reducing the side effects and improving patient compliance. The patents on topical delivery of NSAIDS (US 9012402 B1, US 9072659 B2, US 20150258196 A1) and patents indicating use of herbal penetration enhancers (US 20100273746A1, WO 2005009510 A2, US 6004969 A) helped in selecting the drug, excipients. Current protocol employs various extracts of Piper cubeba fruit to evaluate its role in absorption of NPRS. Various batches containing 1% NPRS and varying concentrations of synthetic permeation enhancers or the extracts were formulated in carbopol gel. Gel was evaluated for parameters like organoleptic parameters, pH, viscosity and spreadability. An ex-vivo percutaneous absorption of NPRS from gel was investigated and compared with best performing synthetic enhancer, transcutol P (TP). The batch containing 2% n-hexane extract (NHE) of Piper cubeba showed higher permeation than TP and Chloroform (CE), Methanolic (ME) and aqueous (AE) extracts as well. It showed improved % cumulative release (85.09%) and flux (278.61μg/cm2.h), as compared to TP and other extracts. Histopathology indicated the formulation safer as compared to that with synthetic enhancer. It suggests P. cubeba as effective and safer tool for transdermal delivery and acts as therapeutic facilitator for naproxen. GC-MS analysis indicates lignans & terpenes in NHE to which this permeation enhancement activity may be attributed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Active intestinal drug absorption and the solubility-permeability interplay.

    Science.gov (United States)

    Porat, Daniel; Dahan, Arik

    2018-02-15

    The solubility-permeability interplay deals with the question: what is the concomitant effect on the drug's apparent permeability when increasing the apparent solubility with a solubility-enabling formulation? The solubility and the permeability are closely related, exhibit certain interplay between them, and ongoing research throughout the past decade shows that treating the one irrespectively of the other may be insufficient. The aim of this article is to provide an overview of the current knowledge on the solubility-permeability interplay when using solubility-enabling formulations for oral lipophilic drugs, highlighting active permeability aspects. A solubility-enabling formulation may affect the permeability in opposite directions; the passive permeability may decrease as a result of the apparent solubility increase, according to the solubility-permeability tradeoff, but at the same time, certain components of the formulation may inhibit/saturate efflux transporters (when relevant), resulting in significant apparent permeability increase. In these cases, excipients with both solubilizing and e.g. P-gp inhibitory properties may lead to concomitant increase of both the solubility and the permeability. Intelligent development of such formulation will account for the simultaneous effects of the excipients' nature/concentrations on the two arms composing the overall permeability: the passive and the active arms. Overall, thorough mechanistic understanding of the various factors involved in the solubility-permeability interplay may allow developing better solubility-enabling formulations, thereby exploiting the advantages analyzed in this article, offering oral delivery solution even for BCS class IV drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Bile salts and their importance for drug absorption

    DEFF Research Database (Denmark)

    Holm, René; Müllertz, Anette; Mu, Huiling

    2013-01-01

    Bile salts are present in the intestines of humans as well as the animals used during the development of pharmaceutical products. This review provides a short introduction into the physical chemical properties of bile salts, a description of the bile concentration and composition of bile...... in different animal species and an overview of the literature investigating the influence of bile salts on the in vivo performance of different compounds and drug formulations. Generally, there is a positive effect on bioavailability when bile is present in the gastro-intestinal tract, independent...

  16. Hydrodynamic Impacts on Dissolution, Transport and Absorption from Thousands of Drug Particles Moving within the Intestines

    Science.gov (United States)

    Behafarid, Farhad; Brasseur, James G.

    2017-11-01

    Following tablet disintegration, clouds of drug particles 5-200 μm in diameter pass through the intestines where drug molecules are absorbed into the blood. Release rate depends on particle size, drug solubility, local drug concentration and the hydrodynamic environment driven by patterned gut contractions. To analyze the dynamics underlying drug release and absorption, we use a 3D lattice Boltzmann model of the velocity and concentration fields driven by peristaltic contractions in vivo, combined with a mathematical model of dissolution-rate from each drug particle transported through the grid. The model is empirically extended for hydrodynamic enhancements to release rate by local convection and shear-rate, and incorporates heterogeneity in bulk concentration. Drug dosage and solubility are systematically varied along with peristaltic wave speed and volume. We predict large hydrodynamic enhancements (35-65%) from local shear-rate with minimal enhancement from convection. With high permeability boundary conditions, a quasi-equilibrium balance between release and absorption is established with volume and wave-speed dependent transport time scale, after an initial transient and before a final period of dissolution/absorption. Supported by FDA.

  17. Facilitation of Drug Transport across the Blood–Brain Barrier with Ultrasound and Microbubbles

    OpenAIRE

    Meairs, Stephen

    2015-01-01

    Medical treatment options for central nervous system (CNS) diseases are limited due to the inability of most therapeutic agents to penetrate the blood–brain barrier (BBB). Although a variety of approaches have been investigated to open the BBB for facilitation of drug delivery, none has achieved clinical applicability. Mounting evidence suggests that ultrasound in combination with microbubbles might be useful for delivery of drugs to the brain through transient opening of the BBB. This techni...

  18. Concomitant intake of alcohol may increase the absorption of poorly soluble drugs.

    Science.gov (United States)

    Fagerberg, Jonas H; Sjögren, Erik; Bergström, Christel A S

    2015-01-25

    Ethanol can increase the solubility of poorly soluble and hence present a higher drug concentration in the gastrointestinal tract. This may produce a faster and more effective absorption resulting in variable and/or high drug plasma concentrations, both of which can lead to adverse drug reactions. In this work we therefore studied the solubility and absorption effects of nine diverse compounds when ethanol was present. The apparent solubility was measured using the μDiss Profiler Plus (pION, MA) in four media representing gastric conditions with and without ethanol. The solubility results were combined with in-house data on solubility in intestinal fluids (with and without ethanol) and pharmacokinetic parameters extracted from the literature and used as input in compartmental absorption simulations using the software GI-Sim. Apparent solubility increased more than 7-fold for non-ionized compounds in simulated gastric fluid containing 20% ethanol. Compounds with weak base functions (cinnarizine, dipyridamole and terfenadine) were completely ionized at the studied gastric pH and their solubility was therefore unaffected by ethanol. Compounds with low solubility in intestinal media and a pronounced solubility increase due to ethanol in the upper gastric compartments showed an increased absorption in the simulations. The rate of absorption of the acidic compounds indomethacin and indoprofen was slightly increased but the extent of absorption was unaffected as the complete doses were readily absorbed even without ethanol. This was likely due to a high apparent solubility in the intestinal compartment where the weak acids are ionized. The absorption of the studied non-ionizable compounds increased when ethanol was present in the gastric and intestinal media. These results indicate that concomitant intake of alcohol may significantly increase the solubility and hence, the plasma concentration for non-ionizable, lipophilic compounds with the potential of adverse drug

  19. Facilitating adverse drug event detection in pharmacovigilance databases using molecular structure similarity: application to rhabdomyolysis

    Science.gov (United States)

    Vilar, Santiago; Harpaz, Rave; Chase, Herbert S; Costanzi, Stefano; Rabadan, Raul

    2011-01-01

    Background Adverse drug events (ADE) cause considerable harm to patients, and consequently their detection is critical for patient safety. The US Food and Drug Administration maintains an adverse event reporting system (AERS) to facilitate the detection of ADE in drugs. Various data mining approaches have been developed that use AERS to detect signals identifying associations between drugs and ADE. The signals must then be monitored further by domain experts, which is a time-consuming task. Objective To develop a new methodology that combines existing data mining algorithms with chemical information by analysis of molecular fingerprints to enhance initial ADE signals generated from AERS, and to provide a decision support mechanism to facilitate the identification of novel adverse events. Results The method achieved a significant improvement in precision in identifying known ADE, and a more than twofold signal enhancement when applied to the ADE rhabdomyolysis. The simplicity of the method assists in highlighting the etiology of the ADE by identifying structurally similar drugs. A set of drugs with strong evidence from both AERS and molecular fingerprint-based modeling is constructed for further analysis. Conclusion The results demonstrate that the proposed methodology could be used as a pharmacovigilance decision support tool to facilitate ADE detection. PMID:21946238

  20. A new in vitro lipid digestion - in vivo absorption model to evaluate the mechanisms of drug absorption from lipid-based formulations.

    Science.gov (United States)

    Crum, Matthew F; Trevaskis, Natalie L; Williams, Hywel D; Pouton, Colin W; Porter, Christopher J H

    2016-04-01

    In vitro lipid digestion models are commonly used to screen lipid-based formulations (LBF), but in vitro-in vivo correlations are in some cases unsuccessful. Here we enhance the scope of the lipid digestion test by incorporating an absorption 'sink' into the experimental model. An in vitro model of lipid digestion was coupled directly to a single pass in situ intestinal perfusion experiment in an anaesthetised rat. The model allowed simultaneous real-time analysis of the digestion and absorption of LBFs of fenofibrate and was employed to evaluate the influence of formulation digestion, supersaturation and precipitation on drug absorption. Formulations containing higher quantities of co-solvent and surfactant resulted in higher supersaturation and more rapid drug precipitation in vitro when compared to those containing higher quantities of lipid. In contrast, when the same formulations were examined using the coupled in vitro lipid digestion - in vivo absorption model, drug flux into the mesenteric vein was similar regardless of in vitro formulation performance. For some drugs, simple in vitro lipid digestion models may underestimate the potential for absorption from LBFs. Consistent with recent in vivo studies, drug absorption for rapidly absorbed drugs such as fenofibrate may occur even when drug precipitation is apparent during in vitro digestion.

  1. Contact-facilitated drug delivery with Sn2 lipase labile prodrugs optimize targeted lipid nanoparticle drug delivery.

    Science.gov (United States)

    Pan, Dipanjan; Pham, Christine T N; Weilbaecher, Katherine N; Tomasson, Michael H; Wickline, Samuel A; Lanza, Gregory M

    2016-01-01

    Sn2 lipase labile phospholipid prodrugs in conjunction with contact-facilitated drug delivery offer an important advancement in Nanomedicine. Many drugs incorporated into nanosystems, targeted or not, are substantially lost during circulation to the target. However, favorably altering the pharmacokinetics and volume of distribution of systemic drug delivery can offer greater efficacy with lower toxicity, leading to new prolonged-release nanoexcipients. However, the concept of achieving Paul Erhlich's inspired vision of a 'magic bullet' to treat disease has been largely unrealized due to unstable nanomedicines, nanosystems achieving low drug delivery to target cells, poor intracellular bioavailability of endocytosed nanoparticle payloads, and the substantial biological barriers of extravascular particle penetration into pathological sites. As shown here, Sn2 phospholipid prodrugs in conjunction with contact-facilitated drug delivery prevent premature drug diffusional loss during circulation and increase target cell bioavailability. The Sn2 phospholipid prodrug approach applies equally well for vascular constrained lipid-encapsulated particles and micelles the size of proteins that penetrate through naturally fenestrated endothelium in the bone marrow or thin-walled venules of an inflamed microcirculation. At one time Nanomedicine was considered a 'Grail Quest' by its loyal opposition and even many in the field adsorbing the pains of a long-learning curve about human biology and particles. However, Nanomedicine with innovations like Sn2 phospholipid prodrugs has finally made 'made the turn' toward meaningful translational success. © 2015 The Authors. WIREs Nanomedicine and Nanobiotechnology published by Wiley Periodicals, Inc.

  2. Drug-Facilitated Sexual Assault: College Women's Risk Perception and Behavioral Choices

    Science.gov (United States)

    Crawford, Emily; Wright, Margaret O'Dougherty; Birchmeier, Zachary

    2008-01-01

    Objective: The authors investigated relationships among prior victimization, risk perceptions, and behavioral choices in responding to drug-facilitated sexual assault in a college party where alcohol is available. Participants and Methods: From fall 2003 to spring 2004, over 400 female undergraduates rated risk perception following an acquaintance…

  3. Evaluation of skin absorption of drugs from topical and transdermal formulations

    Directory of Open Access Journals (Sweden)

    André Luís Morais Ruela

    Full Text Available ABSTRACT The skin barrier function has been attributed to the stratum corneum and represents a major challenge in clinical practice pertaining to cutaneous administration of drugs. Despite this, a large number of bioactive compounds have been successfully administered via cutaneous administration because of advances in the design of topical and transdermal formulations. In vitro and in vivo evaluations of these novel drug delivery systems are necessary to characterize their quality and efficacy. This review covers the most well-known methods for assessing the cutaneous absorption of drugs as an auxiliary tool for pharmaceutical formulation scientists in the design of drug delivery systems. In vitro methods as skin permeation assays using Franz-type diffusion cells, cutaneous retention and tape-stripping methods to study the cutaneous penetration of drugs, and in vivo evaluations as pre-clinical pharmacokinetic studies in animal models are discussed. Alternative approaches to cutaneous microdialysis are also covered. Recent advances in research on skin absorption of drugs and the effect of skin absorption enhancers, as investigated using confocal laser scanning microscopy, Raman confocal microscopy, and attenuated total reflectance Fourier-transform infrared spectroscopy, are reviewed.

  4. A global epidemiological perspective on the toxicology of drug-facilitated sexual assault: A systematic review.

    Science.gov (United States)

    Anderson, Laura Jane; Flynn, Asher; Pilgrim, Jennifer Lucinda

    2017-04-01

    A systematic review was undertaken to determine the current global prevalence of drug-facilitated sexual assault (DFSA) reported in adults in order to identify trends in the toxicology findings in DFSA around the world over the past 20 years. Databases PubMed, PsycINFO and Scopus were systematically searched using the terms: "drug-facilitated sexual assault", "chemical submission", "date rape", "rape drugs" and "drink-spiking" to identify relevant studies for inclusion in the review. This study focused on adult victims of suspected DFSA aged 16 years and above in which toxicology results were reported. The majority of studies included were published in the United States, followed by the United Kingdom, with only a single study dedicated to this area in both Australia and Europe. Epidemiology, prevalence rates, and toxicology for DFSA appear broadly commensurate across different continents, although there are some differences in how "drug-facilitated sexual assault" is defined, as well as differences in the sensitivity of toxicological analyses. Nonetheless, alcohol is the most commonly detected substance and co-occurrence with other drugs is common. Aside from alcohol there was no other specific drug category associated with DFSA. Cannabinoids and benzodiazepines were frequently detected, but a lack of contextual information made it difficult to establish the extent that these substances contributed to suspected cases of DFSA. This comprehensive review suggests that alcohol intoxication combined with voluntary drug consumption presents the greatest risk factor for DFSA, despite populist perceptions that covert drink-spiking is a common occurrence. There is a need to develop policies that encourage early responders to suspected DFSA (e.g., law enforcement agencies, medical staff, support agencies, etc), to collect detailed information about the individual's licit and illicit drug consumption history, in order to assist in providing appropriate and more thorough

  5. An analytical solution for percutaneous drug absorption: application and removal of the vehicle.

    Science.gov (United States)

    Simon, L; Loney, N W

    2005-10-01

    The methods of Laplace transform were used to solve a mathematical model developed for percutaneous drug absorption. This model includes application and removal of the vehicle from the skin. A system of two linear partial differential equations was solved for the application period. The concentration of the medicinal agent in the skin at the end of the application period was used as the initial condition to determine the distribution of the drug in the skin following instantaneous removal of the vehicle. The influences of the diffusion and partition coefficients, clearance factor and vehicle layer thickness on the amount of drug in the vehicle and the skin were discussed.

  6. Computational Studies of Drug Release, Transport and Absorption in the Human Intestines

    Science.gov (United States)

    Behafarid, Farhad; Brasseur, J. G.; Vijayakumar, G.; Jayaraman, B.; Wang, Y.

    2016-11-01

    Following disintegration of a drug tablet, a cloud of particles 10-200 μm in diameter enters the small intestine where drug molecules are absorbed into the blood. Drug release rate depends on particle size, solubility and hydrodynamic enhancements driven by gut motility. To quantify the interrelationships among dissolution, transport and wall permeability, we apply lattice Boltzmann method to simulate the drug concentration field in the 3D gut released from polydisperse distributions of drug particles in the "fasting" vs. "fed" motility states. Generalized boundary conditions allow for both solubility and gut wall permeability to be systematically varied. We apply a local 'quasi-steady state' approximation for drug dissolution using a mathematical model generalized for hydrodynamic enhancements and heterogeneity in drug release rate. We observe fundamental differences resulting from the interplay among release, transport and absorption in relationship to particle size distribution, luminal volume, motility, solubility and permeability. For example, whereas smaller volume encourages higher bulk concentrations and reduced release rate, it also encourages higher absorption rate, making it difficult to generalize predictions. Supported by FDA.

  7. Application of Absorption Modeling in Rational Design of Drug Product Under Quality-by-Design Paradigm.

    Science.gov (United States)

    Kesisoglou, Filippos; Mitra, Amitava

    2015-09-01

    Physiologically based absorption models can be an important tool in understanding product performance and hence implementation of Quality by Design (QbD) in drug product development. In this report, we show several case studies to demonstrate the potential application of absorption modeling in rational design of drug product under the QbD paradigm. The examples include application of absorption modeling—(1) prior to first-in-human studies to guide development of a formulation with minimal sensitivity to higher gastric pH and hence reduced interaction when co-administered with PPIs and/or H2RAs, (2) design of a controlled release formulation with optimal release rate to meet trough plasma concentrations and enable QD dosing, (3) understanding the impact of API particle size distribution on tablet bioavailability and guide formulation design in late-stage development, (4) assess impact of API phase change on product performance to guide specification setting, and (5) investigate the effect of dissolution rate changes on formulation bioperformance and enable appropriate specification setting. These case studies are meant to highlight the utility of physiologically based absorption modeling in gaining a thorough understanding of the product performance and the critical factors impacting performance to drive design of a robust drug product that would deliver the optimal benefit to the patients.

  8. Automation of cell-based drug absorption assays in 96-well format using permeable support systems.

    Science.gov (United States)

    Larson, Brad; Banks, Peter; Sherman, Hilary; Rothenberg, Mark

    2012-06-01

    Cell-based drug absorption assays, such as Caco-2 and MDCK-MDR1, are an essential component of lead compound ADME/Tox testing. The permeability and transport data they provide can determine whether a compound continues in the drug discovery process. Current methods typically incorporate 24-well microplates and are performed manually. Yet the need to generate absorption data earlier in the drug discovery process, on an increasing number of compounds, is driving the use of higher density plates. A simple, more efficient process that incorporates 96-well permeable supports and proper instrumentation in an automated process provides more reproducible data compared to manual methods. Here we demonstrate the ability to perform drug permeability and transport assays using Caco-2 or MDCKII-MDR1 cells. The assay procedure was automated in a 96-well format, including cell seeding, media and buffer exchanges, compound dispense, and sample removal using simple robotic instrumentation. Cell monolayer integrity was confirmed via transepithelial electrical resistance and Lucifer yellow measurements. Proper cell function was validated by analyzing apical-to-basolateral and basolateral-to-apical movement of rhodamine 123, a known P-glycoprotein substrate. Apparent permeability and efflux data demonstrate how the automated procedure provides a less variable method than manual processing, and delivers a more accurate assessment of a compound's absorption characteristics.

  9. Using servant leadership to facilitate healing after a drug diversion experience.

    Science.gov (United States)

    Ramer, Lynne Marie

    2008-08-01

    Although much has been written about substance abuse in nursing, little attention has been paid to the reaction of a nurse's coworkers after he or she has been caught diverting drugs. The remaining staff members may enter into a grieving process, which can have a serious effect on the delivery of patient care and staff satisfaction. Devoting time and energy to addressing the challenges faced by staff members after a drug diversion experience is essential to reestablishing equilibrium in the department. Using the servant leadership model, managers can exemplify the characteristics of commitment, persuasion, awareness, and foresight to facilitate the grieving process and solidify staff cohesion to help ensure quality patient care.

  10. Cognitive Enhancers for Facilitating Drug Cue Extinction: Insights from Animal Models

    Science.gov (United States)

    Nic Dhonnchadha, Bríd Áine; Kantak, Kathleen M.

    2011-01-01

    Given the success of cue exposure (extinction) therapy combined with a cognitive enhancer for reducing anxiety, it is anticipated that this approach will prove more efficacious than exposure therapy alone in preventing relapse in individuals with substance use disorders. Several factors may undermine the efficacy of exposure therapy for substance use disorders, but we suspect that neurocognitive impairments associated with chronic drug use are an important contributing factor. Numerous insights on these issues are gained from research using animal models of addiction. In this review, the relationship between brain sites whose learning, memory and executive functions are impaired by chronic drug use and brain sites that are important for effective drug cue extinction learning is explored first. This is followed by an overview of animal research showing improved treatment outcome for drug addiction (e.g. alcohol, amphetamine, cocaine, heroin) when explicit extinction training is conducted in combination with acute dosing of a cognitive-enhancing drug. The mechanism by which cognitive enhancers are thought to exert their benefits is by facilitating consolidation of drug cue extinction memory after activation of glutamatergic receptors. Based on the encouraging work in animals, factors that may be important for the treatment of drug addiction are considered. PMID:21295059

  11. Circumvention of the tumor membrane barrier to WR-2721 absorption by reduction of drug hydrophilicity

    International Nuclear Information System (INIS)

    Yuhas, J.M.; Davis, M.E.; Glover, D.; Brown, D.Q.; Ritter, M.

    1982-01-01

    In attempting to account for the ability of most solid tumors to restrict the absorption of WR-2721, aminopropyl-aminoethylphosphorothioate, we examined a number of drug characteristics which might allow for this restriction, and observed that drug hypdrophilicity was a major contributing factor. When the highly hydrophilic WR-2721 was dephosphorylated, the drug became less hydrophilic and could readily cross tumor cell membranes. In addition, conventional radioprotectants, such as cysteine and mercaptoethylamine, were shown to be less hydrophilic than WR-2721 and also to cross tumor membranes readily. Therefore, drug hydrophilicity would appear to be the factor underlying the ability of WR-2721 to selectively protect normal tissues while most other protectors alter the radiation resistance of normal and tumor tissue alike. A red blood cell model for studying this problem in greater detail is described

  12. Facilitation of Drug Transport across the Blood–Brain Barrier with Ultrasound and Microbubbles

    Directory of Open Access Journals (Sweden)

    Stephen Meairs

    2015-08-01

    Full Text Available Medical treatment options for central nervous system (CNS diseases are limited due to the inability of most therapeutic agents to penetrate the blood–brain barrier (BBB. Although a variety of approaches have been investigated to open the BBB for facilitation of drug delivery, none has achieved clinical applicability. Mounting evidence suggests that ultrasound in combination with microbubbles might be useful for delivery of drugs to the brain through transient opening of the BBB. This technique offers a unique non-invasive avenue to deliver a wide range of drugs to the brain and promises to provide treatments for CNS disorders with the advantage of being able to target specific brain regions without unnecessary drug exposure. If this method could be applied for a range of different drugs, new CNS therapeutic strategies could emerge at an accelerated pace that is not currently possible in the field of drug discovery and development. This article reviews both the merits and potential risks of this new approach. It assesses methods used to verify disruption of the BBB with MRI and examines the results of studies aimed at elucidating the mechanisms of opening the BBB with ultrasound and microbubbles. Possible interactions of this novel delivery method with brain disease, as well as safety aspects of BBB disruption with ultrasound and microbubbles are addressed. Initial translational research for treatment of brain tumors and Alzheimer’s disease is presented.

  13. Facilitation of Drug Transport across the Blood-Brain Barrier with Ultrasound and Microbubbles.

    Science.gov (United States)

    Meairs, Stephen

    2015-08-31

    Medical treatment options for central nervous system (CNS) diseases are limited due to the inability of most therapeutic agents to penetrate the blood-brain barrier (BBB). Although a variety of approaches have been investigated to open the BBB for facilitation of drug delivery, none has achieved clinical applicability. Mounting evidence suggests that ultrasound in combination with microbubbles might be useful for delivery of drugs to the brain through transient opening of the BBB. This technique offers a unique non-invasive avenue to deliver a wide range of drugs to the brain and promises to provide treatments for CNS disorders with the advantage of being able to target specific brain regions without unnecessary drug exposure. If this method could be applied for a range of different drugs, new CNS therapeutic strategies could emerge at an accelerated pace that is not currently possible in the field of drug discovery and development. This article reviews both the merits and potential risks of this new approach. It assesses methods used to verify disruption of the BBB with MRI and examines the results of studies aimed at elucidating the mechanisms of opening the BBB with ultrasound and microbubbles. Possible interactions of this novel delivery method with brain disease, as well as safety aspects of BBB disruption with ultrasound and microbubbles are addressed. Initial translational research for treatment of brain tumors and Alzheimer's disease is presented.

  14. Multi-purposable filaments of HPMC for 3D printing of medications with tailored drug release and timed-absorption.

    Science.gov (United States)

    Kadry, Hossam; Al-Hilal, Taslim A; Keshavarz, Ali; Alam, Farzana; Xu, Changxue; Joy, Abraham; Ahsan, Fakhrul

    2018-04-20

    Three-dimensional printing (3DP), though developed for nonmedical applications and once regarded as futuristic only, has recently been deployed for the fabrication of pharmaceutical products. However, the existing feeding materials (inks and filaments) that are used for printing drug products have various shortcomings, including the lack of biocompatibility, inadequate extrudability and printability, poor drug loading, and instability. Here, we have sought to develop a filament using a single pharmaceutical polymer, with no additives, which can be multi-purposed and manipulated by computational design for the preparation of tablets with desired release and absorption patterns. As such, we have used hydroxypropyl-methylcellulose (HPMC) and diltiazem, a model drug, to prepare both drug-free and drug-impregnated filaments, and investigated their thermal and crystalline properties, studied the cytotoxicity of the filaments, designed and printed tablets with various infill densities and patterns. By alternating the drug-free and drug-impregnated filaments, we fabricated various types of tablets, studied the drug release profiles, and assessed oral absorption in rats. Both diltiazem and HPMC were stable at extrusion and printing temperatures, and the drug loading was 10% (w/w). The infill density, as well as infill patterns, influenced the drug release profile, and thus, when the infill density was increased to 100%, the percentage of drug released dramatically declined. Tablets with alternating drug-free and drug-loaded layers showed delayed and intermittent drug release, depending on when the drug-loaded layers encountered the dissolution media. Importantly, the oral absorption patterns accurately reproduced the drug release profiles and showed immediate, extended, delayed and episodic absorption of the drug from the rat gastrointestinal tract (GIT). Overall, we have demonstrated here that filaments for 3D printers can be prepared from a pharmaceutical polymer with no

  15. Absorption-desorption of drugs in porous polymers obtained by plasma

    International Nuclear Information System (INIS)

    Gonzalez T, M.

    2016-01-01

    A study about drug absorption and release in plasma polymers is presented in this work, these materials can be used as implants in the human body. In these applications the polymer should be biocompatible and/or biodegradable. Poly pyrroles and poly allylamine s synthesized by plasma have amine groups in their structure which makes them biocompatible with potential as drug carriers. In this function, the polymers were lyophilized to induce pores where the drug can be hosted. Drug-polymer mixtures with 1:10 ratio were prepared. The mixture morphology was studied by Scanning Electron Microscopy while their chemical structure was studied by Infrared Spectroscopy and X-ray Photoelectron Spectroscopy. Two models were studied to assess drug release, dynamic and static, in two solutions: water and Krebs Ringer (Kr) using the UV characteristic absorbance of each drug. In the static model release, 5 mg of the mixture were placed in 10 ml of solution. In the dynamic model, the release was performed with 5 mg of the mixture in 10 ml of solution, 1.5 ml of release medium was removed for UV analysis and replaced with an equal volume of fresh medium. The results indicate that the morphology of the polymers was modified with the lyophilization, in Poly pyrrole pores were induced with diameter in the range of 0.7 to 19 μm, while in Polyallyl amine the surface changed from smooth to rough. Drugs were absorbed in Poly pyrrole by filling the pores first and then coating the polymer with a drug layer. In Poly allylamine the drugs adhered to the polymer surface. Analyzing the atomic orbitals of the mixtures, it was found that the drugs interacted with the polymer. The most affected orbital was S2p, whose separation between 1/2 and 3/2 sub orbitals increased from 0.9 eV in Dapsone and Heparin to 4 eV in the mixtures, where the oxidation state changed from valence 6 to 6 and 2 in the mixtures. This suggests physicochemical interaction between drug and polymer. The drugs were released

  16. A review of drug-facilitated sexual assault evidence: an Irish perspective.

    LENUS (Irish Health Repository)

    McBrierty, Dermot

    2013-05-01

    Drug-facilitated sexual assault (DFSA) is prevalent in Western society. There is a significant degree of confusion regarding the definition and prevalence of DFSA. It is a subject with medical, scientific and legal aspects. These facets are explored in this review through a detailed examination of published data. The legal issues are defined in the context of the Irish judicial system. Several key case-law studies are presented to aid in understanding unresolved difficulties that persist in this complex field of forensics. The aim of this paper is to aid individuals from disparate disciplines to increase their evidence base in the complex and evolving issue of DFSA.

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

    Directory of Open Access Journals (Sweden)

    Ryan D. Rykhus

    2017-12-01

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

  18. Improved intestinal absorption of a poorly water-soluble oral drug using mannitol microparticles containing a nanosolid drug dispersion.

    Science.gov (United States)

    Nishino, Yukiko; Kubota, Aya; Kanazawa, Takanori; Takashima, Yuuki; Ozeki, Tetsuya; Okada, Hiroaki

    2012-11-01

    A nozzle for a spray dryer that can prepare microparticles of water-soluble carriers containing various nanoparticles in a single step was previously developed in our laboratory. To enhance the solubility and intestinal absorption of poorly water-soluble drugs, we used probucol (PBL) as a poorly water-soluble drug, mannitol (MAN) as a water-soluble carrier for the microparticles, and EUDRAGIT (EUD) as a polymer vehicle for the solid dispersion. PBL-EUD-acetone-methanol and aqueous MAN solutions were simultaneously supplied through different liquid passages of the spray nozzle and dried together. PBL-EUD solid dispersion was nanoprecipitated in the MAN solution using an antisolvent mechanism and rapidly dried by surrounding it with MAN. PBL in the dispersion vehicle was amorphous and had higher physical stability according to powder X-ray diffraction and differential scanning calorimetry analysis. The bioavailability of PBL in PBL-EUD S-100-MAN microparticles after oral administration in rats was markedly higher (14- and 6.2-fold, respectively) than that of the original PBL powder and PBL-MAN microparticles. These results demonstrate that the composite microparticles containing a nanosized solid dispersion of a poorly water-soluble drug prepared using the spray nozzle developed by us should be useful to increase the solubility and bioavailability of drugs after oral administration. Copyright © 2012 Wiley Periodicals, Inc.

  19. Facilitators and barriers to the successful implementation of pediatric antibacterial drug trials: Findings from CTTI's survey of investigators

    Directory of Open Access Journals (Sweden)

    Amy Corneli

    2018-03-01

    Full Text Available An urgent need exists to develop new antibacterial drugs for children. We conducted research with investigators of pediatric antibacterial drug trials to identify facilitators and barriers in the conduct of these trials. Seventy-three investigators completed an online survey assessing the importance of 15 facilitators (grouped in 5 topical categories and the severity of 36 barriers (grouped in 6 topical categories to implementing pediatric antibacterial drug trials. Analysis focused on the identification of key factors that facilitate the successful implementation of pediatric antibacterial drug trials and the key barriers to implementation. Almost all investigators identified two factors as very important facilitators: having site personnel for enrollment and having adequate funding. Other top factors were related to staffing. Among the barriers, factors related to parent concerns and consent were prominent, particularly obtaining parental consent when there was disagreement between parents, concerns about the number of blood draws, and concerns about the number of invasive procedures. Having overly narrow eligibility criteria was also identified as a major barrier. The survey findings suggest three areas in which to focus efforts to help facilitate ongoing drug development: (1 improving engagement with parents of children who may be eligible to enroll in a pediatric antibacterial drug trial, (2 broadening inclusion criteria to allow more participants to enroll, and (3 ensuring adequate staffing and establishing sustainable financial strategies, such as funding pediatric trial networks. The pediatric antibacterial drug trials enterprise is likely to benefit from focused efforts by all stakeholders to remove barriers and enhance facilitation.

  20. A reaction limited in vivo dissolution model for the study of drug absorption: Towards a new paradigm for the biopharmaceutic classification of drugs.

    Science.gov (United States)

    Macheras, Panos; Iliadis, Athanassios; Melagraki, Georgia

    2018-05-30

    The aim of this work is to develop a gastrointestinal (GI) drug absorption model based on a reaction limited model of dissolution and consider its impact on the biopharmaceutic classification of drugs. Estimates for the fraction of dose absorbed as a function of dose, solubility, reaction/dissolution rate constant and the stoichiometry of drug-GI fluids reaction/dissolution were derived by numerical solution of the model equations. The undissolved drug dose and the reaction/dissolution rate constant drive the dissolution rate and determine the extent of absorption when high-constant drug permeability throughout the gastrointestinal tract is assumed. Dose is an important element of drug-GI fluids reaction/dissolution while solubility exclusively acts as an upper limit for drug concentrations in the lumen. The 3D plots of fraction of dose absorbed as a function of dose and reaction/dissolution rate constant for highly soluble and low soluble drugs for different "stoichiometries" (0.7, 1.0, 2.0) of the drug-reaction/dissolution with the GI fluids revealed that high extent of absorption was found assuming high drug- reaction/dissolution rate constant and high drug solubility. The model equations were used to simulate in vivo supersaturation and precipitation phenomena. The model developed provides the theoretical basis for the interpretation of the extent of drug's absorption on the basis of the parameters associated with the drug-GI fluids reaction/dissolution. A new paradigm emerges for the biopharmaceutic classification of drugs, namely, a model independent biopharmaceutic classification scheme of four drug categories based on either the fulfillment or not of the current dissolution criteria and the high or low % drug metabolism. Copyright © 2018. Published by Elsevier B.V.

  1. Influence of pH on Drug Absorption from the Gastrointestinal Tract: A Simple Chemical Model

    Science.gov (United States)

    Hickman, Raymond J. S.; Neill, Jane

    1997-07-01

    A simple model of the gastrointestinal tract is obtained by placing ethyl acetate in contact with water at pH 2 and pH 8 in separate test tubes. The ethyl acetate corresponds to the lipid material lining the tract while the water corresponds to the aqueous contents of the stomach (pH 2) and intestine (pH 8). The compounds aspirin, paracetamol and 3-aminophenol are used as exemplars of acidic, neutral and basic drugs respectively to illustrate the influence which pH has on the distribution of each class of drug between the aqueous and organic phases of the model. The relative concentration of drug in the ethyl acetate is judged by applying microlitre-sized samples of ethyl acetate to a layer of fluorescent silica which, after evaporation of the ethyl acetate, is viewed under an ultraviolet lamp. Each of the three drugs, if present in the ethyl acetate, becomes visible as a dark spot on the silica layer. The observations made in the model system correspond well to the patterns of drug absorption from the gastrointestinal tract described in pharmacology texts and these observations are convincingly explained in terms of simple acid-base chemistry.

  2. Pharmacy Student Facilitation of Reporting of Adverse Drug Reactions in a Hospital.

    Science.gov (United States)

    Wentzell, Jason; Nguyen, Tiffany; Bui, Stephanie; MacDonald, Erika

    2017-01-01

    Health Canada relies on health professionals to voluntarily report adverse reactions to the Canada Vigilance Program. Current rates of reporting adverse drug reactions (ADRs) are inadequate to detect important safety issues. To assess the impact of pharmacy student facilitation of ADR reporting by pharmacists at a tertiary care teaching hospital in Canada. The intervention of interest, implemented at one campus of the hospital, was facilitation of ADR reporting by pharmacy students. The students received training on how to submit ADR reports and presented information sessions on the topic to hospital pharmacists; the pharmacists were then encouraged to report ADRs to a designated student for formal reporting. Frequency of reporting by pharmacists at the intervention campus was compared with reporting at a control campus of the same hospital. Data were collected prospectively over a 6-month pilot period, starting in April 2015. During the pilot period, 27 ADR reports were submitted at the intervention campus, and 3 reports at the control campus. All student participants strongly agreed that they would recommend that responsibility for submitting ADR reports to the Canada Vigilance Program remain with pharmacy students during future rotations. Availability of a pharmacy student to facilitate reporting of ADRs may increase the frequency of ADR reporting and could alleviate pharmacist workload; this activity is also a potentially valuable learning experience for students.

  3. The Effect of Digestion and Drug Load on Halofantrine Absorption from Self-nanoemulsifying Drug Delivery System (SNEDDS)

    DEFF Research Database (Denmark)

    Michaelsen, Maria Hotoft; Wasan, Kishor M.; Sivak, Olena

    2016-01-01

    A super-saturated self-nanoemulsifying drug delivery system (super-SNEDDS), containing the poorly water-soluble drug halofantrine (Hf) at 150% of equilibrium solubility (Seq), was compared in vitro and in vivo with a conventional SNEDDS (75% of Seq) with respect to bioavailability and digestibility....... Further, the effect of digestion on oral absorption of Hf from SNEDDS and super-SNEDDS was assessed by incorporation of the lipase inhibitor tetrahydrolipstatin (orlistat) into the SNEDDS. The SNEDDS contained soybean oil/Maisine 34-I (1:1), Kolliphor RH40, and ethanol at a ratio of 55:35:10, w/w percent....... For the dynamic in vitro lipolysis, the precipitation of Hf at 60 min was significantly larger for the super-SNEDDS (66.8 ± 16.4%) than for the SNEDDS (18.5 ± 9.2%). The inhibition of the in vitro digestion by orlistat (1% (w/w)) lowered drug precipitation significantly for both the super-SNEDDS (36.8 ± 1...

  4. Analysis of Intra- and Intersubject Variability in Oral Drug Absorption in Human Bioequivalence Studies of 113 Generic Products.

    Science.gov (United States)

    Sugihara, Masahisa; Takeuchi, Susumu; Sugita, Masaru; Higaki, Kazutaka; Kataoka, Makoto; Yamashita, Shinji

    2015-12-07

    In this study, the data of 113 human bioequivalence (BE) studies of immediate release (IR) formulations of 74 active pharmaceutical ingredients (APIs) conducted at Sawai Pharmaceutical Co., Ltd., was analyzed to understand the factors affecting intra- and intersubject variabilities in oral drug absorption. The ANOVA CV (%) calculated from area under the time-concentration curve (AUC) in each BE study was used as an index of intrasubject variability (Vintra), and the relative standard deviation (%) in AUC was used as that of intersubject variability (Vinter). Although no significant correlation was observed between Vintra and Vinter of all drugs, Vintra of class 3 drugs was found to increase in association with a decrease in drug permeability (P(eff)). Since the absorption of class 3 drugs was rate-limited by the permeability, it was suggested that, for such drugs, the low P(eff) might be a risk factor to cause a large intrasubject variability. To consider the impact of poor water solubility on the variability in BE study, a parameter of P(eff)/Do (Do; dose number) was defined to discriminate the solubility-limited and dissolution-rate-limited absorption of class 2 drugs. It was found that the class 2 drugs with a solubility-limited absorption (P(eff)/Do high intrasubject variability. Furthermore, as a reason for high intra- or intersubject variability in AUC for class 1 drugs, effects of drug metabolizing enzymes were investigated. It was demonstrated that intrasubject variability was high for drugs metabolized by CYP3A4 while intersubject variability was high for drugs metabolized by CYP2D6. For CYP3A4 substrate drugs, the Km value showed the significant relation with Vintra, indicating that the affinity to the enzyme can be a parameter to predict the risk of high intrasubject variability. In conclusion, by analyzing the in house data of human BE study, low permeability, solubility-limited absorption, and high affinity to CYP3A4 are identified as risk factors for

  5. [A prospective study of drug-facilitated sexual assault in Barcelona].

    Science.gov (United States)

    Xifró-Collsamata, Alexandre; Pujol-Robinat, Amadeo; Barbería-Marcalain, Eneko; Arroyo-Fernández, Amparo; Bertomeu-Ruiz, Antonia; Montero-Núñez, Francisco; Medallo-Muñiz, Jordi

    2015-05-08

    To determine the frequency and characteristics of suspected drug-facilitated sexual assault (DFSA) among the victims of sexual assault in Barcelona. Prospective study of every adult consulting an emergency service because of alleged sexual assault and receiving forensic assessment in the city of Barcelona in 2011. A total of 35 of 114 cases (30.7%) met suspected DFSA criteria. Compared with the other victims, suspected DFSA cases were more likely to experience amnesia, to have been assaulted by night, after a social situation and by a recently acquainted man, to have used alcohol before the assault and to be foreigners. In this group ethanol was detected in blood or urine in 48.4% of analyzed cases; their mean back calculated blood alcohol concentration was 2.29g/l (SD 0.685). Also, at least one central nervous system drug other than ethanol was detected in 60,6%, mainly stimulant drugs of abuse. Suspected DFSA is frequent among victims of alleged sexual assault in Barcelona nowadays. The depressor substance most commonly encountered is alcohol, which contributes to victims' vulnerability. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  6. Cyanobacteria: photosynthetic factories combining biodiversity, radiation resistance, and genetics to facilitate drug discovery.

    Science.gov (United States)

    Cassier-Chauvat, Corinne; Dive, Vincent; Chauvat, Franck

    2017-02-01

    Cyanobacteria are ancient, abundant, and widely diverse photosynthetic prokaryotes, which are viewed as promising cell factories for the ecologically responsible production of chemicals. Natural cyanobacteria synthesize a vast array of biologically active (secondary) metabolites with great potential for human health, while a few genetic models can be engineered for the (low level) production of biofuels. Recently, genome sequencing and mining has revealed that natural cyanobacteria have the capacity to produce many more secondary metabolites than have been characterized. The corresponding panoply of enzymes (polyketide synthases and non-ribosomal peptide synthases) of interest for synthetic biology can still be increased through gene manipulations with the tools available for the few genetically manipulable strains. In this review, we propose to exploit the metabolic diversity and radiation resistance of cyanobacteria, and when required the genetics of model strains, for the production and radioactive ( 14 C) labeling of bioactive products, in order to facilitate the screening for new drugs.

  7. In Vitro Characterization of the Biomimetic Properties of Poly(dimethylsiloxane) To Simulate Oral Drug Absorption.

    Science.gov (United States)

    Sinko, Patrick D; Gidley, David; Vallery, Richard; Lamoureux, Aaron; Amidon, Gordon L; Amidon, Gregory E

    2017-12-04

    The potential use of poly(dimethylsiloxane) (PDMS) as an in vitro biomimetic analogue of the passive drug absorption process in the human gastrointestinal tract (GI) is assessed. PDMS is biomimetic because of similarities in small molecule transport, such as mechanism, ionization selectivity, lipophilicity. Nine molecular probes are used to evaluate the transport pathways and properties used to predict human oral absorption rates. The transport pathways through PDMS (bulk/pore) are analogous to transcellular (TCDT) and paracellular (PCDT) drug transport pathways. PDMS PCDT is assessed using positronium annihilation lifetime spectroscopy (PALS) and partition experiments; TCDT using diffusion and partition experiments. PALS determined that PDMS pores were uniform (D ∼ 0.85 nm), isolated, and void volume was unaffected by drug accumulation after equilibrium partitioning. Therefore, there is no PCDT or convective flow through PDMS. A strong linear correlation exists between predicted octanol-water partition coefficients and PDMS partition coefficients (LogK PDMS = 0.736 × LogP O-W - 0.971, R 2 = 0.981). The pH-partition hypothesis is confirmed in PDMS using ibuprofen over pH 2-12. Diffusivity through PDMS is a function of lipophilicity and polar surface area K × D PDMS = 4.46 × 10 -8 × e 2.91×LogK PDMS (R 2 = 0.963) and [Formula: see text] (R 2 = 0.973). Varying the mass% of curing agent changed the lipophilicity and diffusivity (p < 0.02), but not practically (K × D = 2.23 × 10 -5 cm 2 s -1 vs 2.60 × 10 -5 cm 2 s -1 ), and does affect elastic modulus (3.2% = 0.3 MPa to 25% = 3.2 MPa).

  8. In Vitro-In Vivo Predictive Dissolution-Permeation-Absorption Dynamics of Highly Permeable Drug Extended-Release Tablets via Drug Dissolution/Absorption Simulating System and pH Alteration.

    Science.gov (United States)

    Li, Zi-Qiang; Tian, Shuang; Gu, Hui; Wu, Zeng-Guang; Nyagblordzro, Makafui; Feng, Guo; He, Xin

    2018-05-01

    Each of dissolution and permeation may be a rate-limiting factor in the absorption of oral drug delivery. But the current dissolution test rarely took into consideration of the permeation property. Drug dissolution/absorption simulating system (DDASS) valuably gave an insight into the combination of drug dissolution and permeation processes happening in human gastrointestinal tract. The simulated gastric/intestinal fluid of DDASS was improved in this study to realize the influence of dynamic pH change on the complete oral dosage form. To assess the effectiveness of DDASS, six high-permeability drugs were chosen as model drugs, including theophylline (pK a1  = 3.50, pK a2  = 8.60), diclofenac (pK a  = 4.15), isosorbide 5-mononitrate (pK a  = 7.00), sinomenine (pK a  = 7.98), alfuzosin (pK a  = 8.13), and metoprolol (pK a  = 9.70). A general elution and permeation relationship of their commercially available extended-release tablets was assessed as well as the relationship between the cumulative permeation and the apparent permeability. The correlations between DDASS elution and USP apparatus 2 (USP2) dissolution and also between DDASS permeation and beagle dog absorption were developed to estimate the predictability of DDASS. As a result, the common elution-dissolution relationship was established regardless of some variance in the characteristic behavior between DDASS and USP2 for drugs dependent on the pH for dissolution. Level A in vitro-in vivo correlation between DDASS permeation and dog absorption was developed for drugs with different pKa. The improved DDASS will be a promising tool to provide a screening method on the predictive dissolution-permeation-absorption dynamics of solid drug dosage forms in the early-phase formulation development.

  9. Challenges and strategies to facilitate formulation development of pediatric drug products: Safety qualification of excipients.

    Science.gov (United States)

    Buckley, Lorrene A; Salunke, Smita; Thompson, Karen; Baer, Gerri; Fegley, Darren; Turner, Mark A

    2018-02-05

    A public workshop entitled "Challenges and strategies to facilitate formulation development of pediatric drug products" focused on current status and gaps as well as recommendations for risk-based strategies to support the development of pediatric age-appropriate drug products. Representatives from industry, academia, and regulatory agencies discussed the issues within plenary, panel, and case-study breakout sessions. By enabling practical and meaningful discussion between scientists representing the diversity of involved disciplines (formulators, nonclinical scientists, clinicians, and regulators) and geographies (eg, US, EU), the Excipients Safety workshop session was successful in providing specific and key recommendations for defining paths forward. Leveraging orthogonal sources of data (eg. food industry, agro science), collaborative data sharing, and increased awareness of the existing sources such as the Safety and Toxicity of Excipients for Paediatrics (STEP) database will be important to address the gap in excipients knowledge needed for risk assessment. The importance of defining risk-based approaches to safety assessments for excipients vital to pediatric formulations was emphasized, as was the need for meaningful stakeholder (eg, patient, caregiver) engagement. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Focused ultrasound-facilitated brain drug delivery using optimized nanodroplets: vaporization efficiency dictates large molecular delivery

    Science.gov (United States)

    Wu, Shih-Ying; Fix, Samantha M.; Arena, Christopher B.; Chen, Cherry C.; Zheng, Wenlan; Olumolade, Oluyemi O.; Papadopoulou, Virginie; Novell, Anthony; Dayton, Paul A.; Konofagou, Elisa E.

    2018-02-01

    Focused ultrasound with nanodroplets could facilitate localized drug delivery after vaporization with potentially improved in vivo stability, drug payload, and minimal interference outside of the focal zone compared with microbubbles. While the feasibility of blood-brain barrier (BBB) opening using nanodroplets has been previously reported, characterization of the associated delivery has not been achieved. It was hypothesized that the outcome of drug delivery was associated with the droplet’s sensitivity to acoustic energy, and can be modulated with the boiling point of the liquid core. Therefore, in this study, octafluoropropane (OFP) and decafluorobutane (DFB) nanodroplets were used both in vitro for assessing their relative vaporization efficiency with high-speed microscopy, and in vivo for delivering molecules with a size relevant to proteins (40 kDa dextran) to the murine brain. It was found that at low pressures (300-450 kPa), OFP droplets vaporized into a greater number of microbubbles compared to DFB droplets at higher pressures (750-900 kPa) in the in vitro study. In the in vivo study, successful delivery was achieved with OFP droplets at 300 kPa and 450 kPa without evidence of cavitation damage using ¼ dosage, compared to DFB droplets at 900 kPa where histology indicated tissue damage due to inertial cavitation. In conclusion, the vaporization efficiency of nanodroplets positively impacted the amount of molecules delivered to the brain. The OFP droplets due to the higher vaporization efficiency served as better acoustic agents to deliver large molecules efficiently to the brain compared with the DFB droplets.

  11. Development of a Unified Dissolution and Precipitation Model and Its Use for the Prediction of Oral Drug Absorption.

    Science.gov (United States)

    Jakubiak, Paulina; Wagner, Björn; Grimm, Hans Peter; Petrig-Schaffland, Jeannine; Schuler, Franz; Alvarez-Sánchez, Rubén

    2016-02-01

    Drug absorption is a complex process involving dissolution and precipitation, along with other kinetic processes. The purpose of this work was to (1) establish an in vitro methodology to study dissolution and precipitation in early stages of drug development where low compound consumption and high throughput are necessary, (2) develop a mathematical model for a mechanistic explanation of generated in vitro dissolution and precipitation data, and (3) extrapolate in vitro data to in vivo situations using physiologically based models to predict oral drug absorption. Small-scale pH-shift studies were performed in biorelevant media to monitor the precipitation of a set of poorly soluble weak bases. After developing a dissolution-precipitation model from this data, it was integrated into a simplified, physiologically based absorption model to predict clinical pharmacokinetic profiles. The model helped explain the consequences of supersaturation behavior of compounds. The predicted human pharmacokinetic profiles closely aligned with the observed clinical data. In summary, we describe a novel approach combining experimental dissolution/precipitation methodology with a mechanistic model for the prediction of human drug absorption kinetics. The approach unifies the dissolution and precipitation theories and enables accurate predictions of in vivo oral absorption by means of physiologically based modeling.

  12. Updates on drug-target network; facilitating polypharmacology and data integration by growth of DrugBank database.

    Science.gov (United States)

    Barneh, Farnaz; Jafari, Mohieddin; Mirzaie, Mehdi

    2016-11-01

    Network pharmacology elucidates the relationship between drugs and targets. As the identified targets for each drug increases, the corresponding drug-target network (DTN) evolves from solely reflection of the pharmaceutical industry trend to a portrait of polypharmacology. The aim of this study was to evaluate the potentials of DrugBank database in advancing systems pharmacology. We constructed and analyzed DTN from drugs and targets associations in the DrugBank 4.0 database. Our results showed that in bipartite DTN, increased ratio of identified targets for drugs augmented density and connectivity of drugs and targets and decreased modular structure. To clear up the details in the network structure, the DTNs were projected into two networks namely, drug similarity network (DSN) and target similarity network (TSN). In DSN, various classes of Food and Drug Administration-approved drugs with distinct therapeutic categories were linked together based on shared targets. Projected TSN also showed complexity because of promiscuity of the drugs. By including investigational drugs that are currently being tested in clinical trials, the networks manifested more connectivity and pictured the upcoming pharmacological space in the future years. Diverse biological processes and protein-protein interactions were manipulated by new drugs, which can extend possible target combinations. We conclude that network-based organization of DrugBank 4.0 data not only reveals the potential for repurposing of existing drugs, also allows generating novel predictions about drugs off-targets, drug-drug interactions and their side effects. Our results also encourage further effort for high-throughput identification of targets to build networks that can be integrated into disease networks. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  13. Hair analysis in toxicological investigation of drug-facilitated crimes in Denmark over a 8-year period

    DEFF Research Database (Denmark)

    Wang, Xin; Johansen, Sys Stybe; Nielsen, Marie Katrine Klose

    2018-01-01

    analgesics, antipsychotics, barbiturates, and illicit drugs from DFC cases. Drug detection in hair in DFC cases following a single or few intakes of chlorprothixene, codeine, diphenhydramine, oxazepam, oxycodone, promethazine, and phenobarbital is reported for the first time in forensic toxicology......Hair can serve as a specimen for identifying past drug exposure. Segmental hair analysis may differentiate a single exposure from chronic use. Consequently, segmental hair analysis is useful for disclosing a single drug ingestion, as well as for determining repeated exposures in drug......-facilitated crimes (DFCs). This paper presents an overview of toxicological investigations that have used hair analysis in DFC cases from 2009 to 2016 in Denmark. Hair concentrations were determined for 24 DFC-related drugs and metabolites, including benzodiazepines and other hypnotics, antihistamines, opioid...

  14. A modified physiological BCS for prediction of intestinal absorption in drug discovery.

    Science.gov (United States)

    Zaki, Noha M; Artursson, Per; Bergström, Christel A S

    2010-10-04

    In this study, the influence of physiologically relevant media on the compound position in a biopharmaceutical classification system (BCS) which resembled the intestinal absorption was investigated. Both solubility and permeability limited compounds (n = 22) were included to analyze the importance of each of these on the final absorption. Solubility was determined in three different dissolution media, phosphate buffer pH 6.5 (PhB 6.5), fasted state simulated intestinal fluid (FaSSIF), and fed state simulated intestinal fluid (FeSSIF) at 37 °C, and permeability values were determined using the 2/4/A1 cell line. The solubility data and membrane permeability values were used for sorting the compounds into a BCS modified to reflect the fasted and fed state. Three of the seven compounds sorted as BCS II in PhB 6.5 (high permeability, low solubility) changed their position to BCS I when dissolved in FaSSIF and/or FeSSIF (high permeability, high solubility). These were low dosed (20 mg or less) lipophilic molecules displaying solvation limited solubility. In contrast, compounds having solid-state limited solubility had a minor increase in solubility when dissolved in FaSSIF and/or FeSSIF. Although further studies are needed to enable general cutoff values, our study indicates that low dosed BCS Class II compounds which have solubility normally restricted by poor solvation may behave as BCS Class I compounds in vivo. The large series of compounds investigated herein reveals the importance of investigating solubility and dissolution under physiologically relevant conditions in all stages of the drug discovery process to push suitable compounds forward, to select proper formulations, and to reduce the risk of food effects.

  15. Strategies to facilitate integrated care for people with alcohol and other drug problems: a systematic review.

    Science.gov (United States)

    Savic, Michael; Best, David; Manning, Victoria; Lubman, Dan I

    2017-04-07

    There is a growing body of research highlighting the potential benefits of integrated care as a way of addressing the needs of people with alcohol and other drug (AOD) problems, given the broad range of other issues clients often experience. However, there has been little academic attention on the strategies that treatment systems, agencies and clinicians could implement to facilitate integrated care. We synthesised the existing evidence on strategies to improve integrated care in an AOD treatment context by conducting a systematic review of the literature. We searched major academic databases for peer-reviewed articles that evaluated strategies that contribute to integrated care in an AOD context between 1990 and 2014. Over 2600 articles were identified, of which 14 met the study inclusion criteria of reporting on an empirical study to evaluate the implementation of integrated care strategies. The types of strategies utilised in included articles were then synthesised. We identified a number of interconnected strategies at the funding, organisational, service delivery and clinical levels. Ensuring that integrated care is included within service specifications of commissioning bodies and is adequately funded was found to be critical in effective integration. Cultivating positive inter-agency relationships underpinned and enabled the implementation of most strategies identified. Staff training in identifying and responding to needs beyond clinicians' primary area of expertise was considered important at a service level. However, some studies highlight the need to move beyond discrete training events and towards longer term coaching-type activities focussed on implementation and capacity building. Sharing of client information (subject to informed consent) was critical for most integrated care strategies. Case-management was found to be a particularly good approach to responding to the needs of clients with multiple and complex needs. At the clinical level, screening

  16. Influences of doping mesoporous magnesium silicate on water absorption, drug release, degradability, apatite-mineralization and primary cells responses to calcium sulfate based bone cements

    International Nuclear Information System (INIS)

    Gu, Zhengrong; Wang, Sicheng; Weng, Weizong; Chen, Xiao; Cao, Liehu; Wei, Jie; Shin, Jung-Woog; Su, Jiacan

    2017-01-01

    In this study, composite cements containing mesoporous magnesium silicate (m-MS) and calcium sulfate (CS) were fabricated. The results revealed that the setting time of the m-MS/CS composite cements (m-MSC) slightly prolonged with the increase of m-MS content while the compressive strength suffered a little loss. The doping of m-MS improved the water absorption, drug release (vancomycin) and degradability of the m-MSC in Tris-HCl solution (pH = 7.4). In addition, addition of m-MS facilitated the apatite-mineralization of m-MSC in simulated body fluid (SBF), indicating good bioactivity. For cell cultural experiments, the results revealed that the m-MSC promoted the cells adhesion and proliferation, and improved the alkaline phosphatase (ALP) activity of MC3T3-E1 cells, revealing good cytocompatibility. It could be suggested that the m-MSC might be promising cements biomaterials for bone tissue regeneration. - Highlights: • The mesoporous magnesium silicate and calcium sulfate composite was fabricated. • The composite possessed good water absorption and drug release of vancomycin. • The bioactive composite could enhance the in vivo apatite formation in SBF. • The composite promoted cell adhesion, proliferation and osteogenic differentiation.

  17. Influences of doping mesoporous magnesium silicate on water absorption, drug release, degradability, apatite-mineralization and primary cells responses to calcium sulfate based bone cements

    Energy Technology Data Exchange (ETDEWEB)

    Gu, Zhengrong [Department of Trauma Orthopaedics, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); The Department of Orthopaedics, Jing' an District Centre Hospital of Shanghai (Huashan Hospital Fudan University Jing' An Branch), 200040 (China); Wang, Sicheng [Department of Trauma Orthopaedics, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Department of Orthopaedics, Zhongye Hospital, Shanghai 200941 (China); Weng, Weizong; Chen, Xiao; Cao, Liehu [Department of Trauma Orthopaedics, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Wei, Jie [Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China); Shin, Jung-Woog [Department of Biomedical Engineering, Inje University, Gimhae, 621749 (Korea, Republic of); Su, Jiacan, E-mail: jiacansu@sina.com [Department of Trauma Orthopaedics, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China)

    2017-06-01

    In this study, composite cements containing mesoporous magnesium silicate (m-MS) and calcium sulfate (CS) were fabricated. The results revealed that the setting time of the m-MS/CS composite cements (m-MSC) slightly prolonged with the increase of m-MS content while the compressive strength suffered a little loss. The doping of m-MS improved the water absorption, drug release (vancomycin) and degradability of the m-MSC in Tris-HCl solution (pH = 7.4). In addition, addition of m-MS facilitated the apatite-mineralization of m-MSC in simulated body fluid (SBF), indicating good bioactivity. For cell cultural experiments, the results revealed that the m-MSC promoted the cells adhesion and proliferation, and improved the alkaline phosphatase (ALP) activity of MC3T3-E1 cells, revealing good cytocompatibility. It could be suggested that the m-MSC might be promising cements biomaterials for bone tissue regeneration. - Highlights: • The mesoporous magnesium silicate and calcium sulfate composite was fabricated. • The composite possessed good water absorption and drug release of vancomycin. • The bioactive composite could enhance the in vivo apatite formation in SBF. • The composite promoted cell adhesion, proliferation and osteogenic differentiation.

  18. Hair analysis in toxicological investigation of drug-facilitated crimes in Denmark over a 8-year period.

    Science.gov (United States)

    Wang, Xin; Johansen, Sys Stybe; Nielsen, Marie Katrine Klose; Linnet, Kristian

    2018-04-01

    Hair can serve as a specimen for identifying past drug exposure. Segmental hair analysis may differentiate a single exposure from chronic use. Consequently, segmental hair analysis is useful for disclosing a single drug ingestion, as well as for determining repeated exposures in drug-facilitated crimes (DFCs). This paper presents an overview of toxicological investigations that have used hair analysis in DFC cases from 2009 to 2016 in Denmark. Hair concentrations were determined for 24 DFC-related drugs and metabolites, including benzodiazepines and other hypnotics, antihistamines, opioid analgesics, antipsychotics, barbiturates, and illicit drugs from DFC cases. Drug detection in hair in DFC cases following a single or few intakes of chlorprothixene, codeine, diphenhydramine, oxazepam, oxycodone, promethazine, and phenobarbital is reported for the first time in forensic toxicology. A literature review on concentrations in the published DFC-related hair cases and on concentrations in hair of these substances after single and multiple doses is included. These cases demonstrate the value of segmental hair analysis in DFCs and facilitate future interpretations of results. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Up-regulation of abscisic acid signaling pathway facilitates aphid xylem absorption and osmoregulation under drought stress.

    Science.gov (United States)

    Guo, Huijuan; Sun, Yucheng; Peng, Xinhong; Wang, Qinyang; Harris, Marvin; Ge, Feng

    2016-02-01

    The activation of the abscisic acid (ABA) signaling pathway reduces water loss from plants challenged by drought stress. The effect of drought-induced ABA signaling on the defense and nutrition allocation of plants is largely unknown. We postulated that these changes can affect herbivorous insects. We studied the effects of drought on different feeding stages of pea aphids in the wild-type A17 of Medicago truncatula and ABA signaling pathway mutant sta-1. We examined the impact of drought on plant water status, induced plant defense signaling via the abscisic acid (ABA), jasmonic acid (JA), and salicylic acid (SA) pathways, and on the host nutritional quality in terms of leaf free amino acid content. During the penetration phase of aphid feeding, drought decreased epidermis/mesophyll resistance but increased mesophyll/phloem resistance of A17 but not sta-1 plants. Quantification of transcripts associated with ABA, JA and SA signaling indicated that the drought-induced up-regulation of ABA signaling decreased the SA-dependent defense but increased the JA-dependent defense in A17 plants. During the phloem-feeding phase, drought had little effect on the amino acid concentrations and the associated aphid phloem-feeding parameters in both plant genotypes. In the xylem absorption stage, drought decreased xylem absorption time of aphids in both genotypes because of decreased water potential. Nevertheless, the activation of the ABA signaling pathway increased water-use efficiency of A17 plants by decreasing the stomatal aperture and transpiration rate. In contrast, the water potential of sta-1 plants (unable to close stomata) was too low to support xylem absorption activity of aphids; the aphids on sta-1 plants had the highest hemolymph osmolarity and lowest abundance under drought conditions. Taken together this study illustrates the significance of cross-talk between biotic-abiotic signaling pathways in plant-aphid interaction, and reveals the mechanisms leading to alter

  20. Erbium:YAG laser resurfacing increases skin permeability and the risk of excessive absorption of antibiotics and sunscreens: the influence of skin recovery on drug absorption.

    Science.gov (United States)

    Lee, Woan-Ruoh; Shen, Shing-Chuan; Al-Suwayeh, Saleh A; Li, Yi-Ching; Fang, Jia-You

    2012-06-01

    While laser skin resurfacing is expected to result in reduced barrier function and increased risk of drug absorption, the extent of the increment has not yet been systematically investigated. We aimed to establish the skin permeation profiles of tetracycline and sunscreens after exposure to the erbium:yttrium-aluminum-garnet (Er:YAG) laser during postoperative periods. Physiological and histopathological examinations were carried out for 5 days after laser treatment on nude mice. Percutaneous absorption of the permeants was determined by an in vitro Franz cell. Ablation depths varied in reaching the stratum corneum (10 μm, 2.5 J/cm²) to approach the epidermis (25 μm, 6.25 J/cm²) and upper dermis (40 μm, 10 J/cm²). Reepithelialization evaluated by transepidermal water loss was complete within 2-4 days and depended on the ablation depth. Epidermal hyperplasia was observed in the 40-μm-treated group. The laser was sufficient to disrupt the skin barrier and allow the transport of the permeants into and across the skin. The laser fluence was found to play an important role in modulating skin absorption. A 25-μm ablation depth increased tetracycline flux 84-fold. A much smaller enhancement (3.3-fold) was detected for tetracycline accumulation within the skin. The laser with different fluences produced enhancement of oxybenzone skin deposition of 3.4-6.4-fold relative to the untreated group. No penetration across the skin was shown regardless of whether titanium dioxide was applied to intact or laser-treated skin. However, laser resurfacing increased the skin deposition of titanium dioxide from 46 to 109-188 ng/g. Tetracycline absorption had recovered to the level of intact skin after 5 days, while more time was required for oxybenzone absorption. The in vivo skin accumulation and plasma concentration revealed that the laser could increase tetracycline absorption 2-3-fold. The experimental results indicated that clinicians should be cautious when determining the

  1. Convective transport of highly plasma protein bound drugs facilitates direct penetration into deep tissues after topical application

    Science.gov (United States)

    Dancik, Yuri; Anissimov, Yuri G; Jepps, Owen G; Roberts, Michael S

    2012-01-01

    AIMS To relate the varying dermal, subcutaneous and muscle microdialysate concentrations found in man after topical application to the nature of the drug applied and to the underlying physiology. METHODS We developed a physiologically based pharmacokinetic model in which transport to deeper tissues was determined by tissue diffusion, blood, lymphatic and intersitial flow transport and drug properties. The model was applied to interpret published human microdialysis data, estimated in vitro dermal diffusion and protein binding affinity of drugs that have been previously applied topically in vivo and measured in deep cutaneous tissues over time. RESULTS Deeper tissue microdialysis concentrations for various drugs in vivo vary widely. Here, we show that carriage by the blood to the deeper tissues below topical application sites facilitates the transport of highly plasma protein bound drugs that penetrate the skin, leading to rapid and significant concentrations in those tissues. Hence, the fractional concentration for the highly plasma protein bound diclofenac in deeper tissues is 0.79 times that in a probe 4.5 mm below a superficial probe whereas the corresponding fractional concentration for the poorly protein bound nicotine is 0.02. Their corresponding estimated in vivo lag times for appearance of the drugs in the deeper probes were 1.1 min for diclofenac and 30 min for nicotine. CONCLUSIONS Poorly plasma protein bound drugs are mainly transported to deeper tissues after topical application by tissue diffusion whereas the transport of highly plasma protein bound drugs is additionally facilitated by convective blood, lymphatic and interstitial transport to deep tissues. PMID:21999217

  2. A study of the energy absorption and exposure buildup factors of some anti-inflammatory drugs

    International Nuclear Information System (INIS)

    Ekinci, Neslihan; Kavaz, Esra; Özdemir, Yüksel

    2014-01-01

    Human radiation exposure is increasing due to radiation development in science and technology. The development of radioprotective agents is important for protecting patients from the side effects of radiotherapy and for protecting the public from unwanted irradiation. Radioprotective agents are used to reduce the damage caused by radiation in healthy tissues. There are several classes of radioprotective compounds that are under investigation. Analgesics and anti-inflammatory compounds are being considered for treating or preventing the effects of damage due to radiation exposure, or for increasing the chance of survival after exposure to a high dose of radiation. In this study, we investigated the radioprotective effects of some analgesic and anti-inflammatory compounds by evaluating buildup factors. The gamma ray energy absorption (EABF) and exposure buildup factors (EBF) were calculated to select compounds in a 0.015–15 MeV energy region up to a penetration depth of 40 mfp (mean free path). Variations of EABF and EBF with incident photon energy and penetration depth elements were also investigated. Significant variations in both EABF and EBF values were observed for several compounds at the moderate energy region. At energies below 0.15 MeV, EABF and EBF values increased with decreasing equivalent atomic number (Z eq ) of the samples. In addition, EABF and EBF were the largest for ibuprofen, aspirin, paracetamol, naproxen and ketoprofen at 0.05 and 0.06 MeV, respectively, and the EABF value was 0.1 MeV for aceclofenac. From these results, we concluded that the buildup of photons is less for aceclofenac compared to other materials. - Highlights: • Buildup factors of anti-inflammatory drugs have been calculated by a G-P fitting method. • Z eff of diclofenac was observed higher than other compounds. • It was found that buildup of photons is less for aceclofenac and diclofenac. • It would be appealing to use aceclofenac and diclofenac as radioprotective

  3. Rapid screening and identification of illicit drugs by IR absorption spectroscopy and gas chromatography

    Science.gov (United States)

    Mengali, Sandro; Liberatore, Nicola; Luciani, Domenico; Viola, Roberto; Cardinali, Gian Carlo; Elmi, Ivan; Poggi, Antonella; Zampolli, Stefano; Biavardi, Elisa; Dalcanale, Enrico; Bonadio, Federica; Delemont, Olivier; Esseiva, Pierre; Romolo, Francesco S.

    2013-01-01

    Analytical instruments based on InfraRed Absorption Spectroscopy (IRAS) and Gas Chromatography (GC) are today available only as bench-top instrumentation for forensic labs and bulk analysis. Within the 'DIRAC' project funded by the European Commission, we are developing an advanced portable sensor, that combines miniaturized GC as its key chemical separation tool, and IRAS in a Hollow Fiber (HF) as its key analytical tool, to detect and recognize illicit drugs and key precursors, as bulk and as traces. The HF-IRAS module essentially consists of a broadly tunable External Cavity (EC) Quantum Cascade Laser (QCL), thermo-electrically cooled MCT detectors, and an infrared hollow fiber at controlled temperature. The hollow fiber works as a miniaturized gas cell, that can be connected to the output of the GC column with minimal dead volumes. Indeed, the module has been coupled to GC columns of different internal diameter and stationary phase, and with a Vapour Phase Pre-concentrator (VPC) that selectively traps target chemicals from the air. The presentation will report the results of tests made with amphetamines and precursors, as pure substances, mixtures, and solutions. It will show that the sensor is capable of analyzing all the chemicals of interest, with limits of detection ranging from a few nanograms to about 100-200 ng. Furthermore, it is suitable to deal with vapours directly trapped from the headspace of a vessel, and with salts treated in a basic solution. When coupled to FAST GC columns, the module can analyze multi-components mixes in less than 5 minutes.

  4. Paracetamol as a Post Prandial Marker for Gastric Emptying, A Food-Drug Interaction on Absorption.

    Directory of Open Access Journals (Sweden)

    R Bartholomé

    Full Text Available The use of paracetamol as tool to determine gastric emptying was evaluated in a cross over study. Twelve healthy volunteers were included and each of them consumed two low and two high caloric meals. Paracetamol was mixed with a liquid meal and administered by a nasogastric feeding tube. The post prandial paracetamol plasma concentration time curve in all participants and the paracetamol concentration in the stomach content in six participants were determined. It was found that after paracetamol has left the stomach, based on analysis of the stomach content, there was still a substantial rise in the plasma paracetamol concentration time curve. Moreover, the difference in gastric emptying between high and low caloric meals was missed using the plasma paracetamol concentration time curve. The latter curves indicate that (i part of the paracetamol may leave the stomach much quicker than the meal and (ii part of the paracetamol may be relatively slowly absorbed in the duodenum. This can be explained by the partition of the homogenous paracetamol-meal mixture in the stomach in an aqueous phase and a solid bolus. The aqueous phase leaves the stomach quickly and the paracetamol in this phase is quickly absorbed in the duodenum, giving rise to the relatively steep increase of the paracetamol concentration in the plasma. The bolus leaves the stomach relatively slowly, and encapsulation by the bolus results in relatively slow uptake of paracetamol from the bolus in the duodenum. These findings implicate that paracetamol is not an accurate post prandial marker for gastric emptying. The paracetamol concentration time curve rather illustrates the food-drug interaction on absorption, which is not only governed by gastric emptying.ClinicalTrials.gov NCT01335503 Nederlands Trial Register NTR2780.

  5. In vivo assessment of the impact of efflux transporter on oral drug absorption using portal vein-cannulated rats.

    Science.gov (United States)

    Matsuda, Yoshiki; Konno, Yoshihiro; Hashimoto, Takashi; Nagai, Mika; Taguchi, Takayuki; Satsukawa, Masahiro; Yamashita, Shinji

    2013-08-01

    The purpose of this study was to evaluate the impact of intestinal efflux transporters on the in vivo oral absorption process. Three model drugs-fexofenadine (FEX), sulfasalazine (SASP), and topotecan (TPT)-were selected as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and P-gp and BCRP substrates, respectively. The drugs were orally administered to portal vein-cannulated rats after pretreatment with zosuquidar (ZSQ), P-gp inhibitor, and/or Ko143, BCRP inhibitor. Intestinal availability (Fa·Fg) of the drugs was calculated from the difference between portal and systemic plasma concentrations. When rats were orally pretreated with ZSQ, Fa·Fg of FEX increased 4-fold and systemic clearance decreased to 75% of the control. In contrast, intravenous pretreatment with ZSQ did not affect Fa·Fg of FEX, although systemic clearance decreased significantly. These data clearly show that the method presented herein using portal vein-cannulated rats can evaluate the effects of intestinal transporters on Fa·Fg of drugs independently of variable systemic clearance. In addition, it was revealed that 71% of FEX taken up into enterocytes underwent selective efflux via P-gp to the apical surface, while 79% of SASP was effluxed by Bcrp. In the case of TPT, both transporters were involved in its oral absorption. Quantitative analysis indicated a 3.5-fold higher contribution from Bcrp than P-gp. In conclusion, the use of portal vein-cannulated rats enabled the assessment of the impact of efflux transporters on intestinal absorption of model drugs. This experimental system is useful for clarifying the cause of low bioavailability of various drugs.

  6. Supersaturation-nucleation behavior of poorly soluble drugs and its impact on the oral absorption of drugs in thermodynamically high-energy forms.

    Science.gov (United States)

    Ozaki, Shunsuke; Minamisono, Takuma; Yamashita, Taro; Kato, Takashi; Kushida, Ikuo

    2012-01-01

    In order to better understand the oral absorption behavior of poorly water-soluble drugs, their supersaturation-nucleation behavior was characterized in fasted state simulated intestinal fluid. The induction time (t(ind)) for nucleation was measured for four model drugs: itraconazole, erlotinib, troglitazone, and PLX4032. Supersaturated solutions were prepared by solvent shift method, and nucleation initiation was monitored by ultraviolet detection. The relationship between t(ind) and degree of supersaturation was analyzed in terms of classical nucleation theory. The defined supersaturation stability proved to be compound specific. Clinical data on oral absorption were investigated for drugs in thermodynamically high-energy forms such as amorphous forms and salts and was compared with in vitro supersaturation-nucleation characteristics. Solubility-limited maximum absorbable dose was proportionate to intestinal effective drug concentrations, which are related to supersaturation stability and thermodynamic solubility. Supersaturation stability was shown to be an important factor in determining the effect of high-energy forms. The characterization of supersaturation-nucleation behavior by the presented method is, therefore, valuable for assessing the potential absorbability of poorly water-soluble drugs. Copyright © 2011 Wiley-Liss, Inc.

  7. Ethanol-drug absorption interaction: potential for a significant effect on the plasma pharmacokinetics of ethanol vulnerable formulations.

    Science.gov (United States)

    Lennernäs, Hans

    2009-01-01

    Generally, gastric emptying of a drug to the small intestine is controlled by gastric motor activity and is the main factor affecting the onset of absorption. Accordingly, the emptying rate from the stomach is mainly affected by the digestive state, the properties of the pharmaceutical formulation and the effect of drugs, posture and circadian rhythm. Variability in the gastric emptying of drugs is reflected in variability in the absorption rate and the shape of the plasma pharmacokinetic profile. When ethanol interacts with an oral controlled release product, such that the mechanism controlling drug release is impaired, the delivery of the dissolved dose into the small intestine and the consequent absorption may result in dangerously high plasma concentrations. For example, the maximal plasma concentration of hydromorphone has individually been shown to be increased as much as 16 times through in vivo testing as a result of this specific pharmacokinetic ethanol-drug formulation interaction. Thus, a pharmacokinetic ethanol-drug interaction is a very serious safety concern when substantially the entire dose from a controlled release product is rapidly emptied into the small intestine (dose dumping), having been largely dissolved in a strong alcoholic beverage in the stomach during a sufficient lag-time in gastric emptying. Based on the literature, a two hour time frame for screening the in vitro dissolution profile of a controlled release product in ethanol concentrations of up to 40% is strongly supported and may be considered as the absolute minimum standard. It is also evident that the dilution, absorption and metabolism of ethanol in the stomach are processes with a minor effect on the local ethanol concentration and that ethanol exposure will be highly dependent on the volume and ethanol concentration of the fluid ingested, together with the rate of intake and gastric emptying. When and in which patients a clinically significant dose dumping will happen is

  8. Mechanism of enhanced oral absorption of morin by phospholipid complex based self-nanoemulsifying drug delivery system.

    Science.gov (United States)

    Zhang, Jinjie; Li, Jianbo; Ju, Yuan; Fu, Yao; Gong, Tao; Zhang, Zhirong

    2015-02-02

    Phospholipid complex (PLC) based self-nanoemulsifying drug delivery system (PLC-SNEDDS) has been developed for efficient delivery of drugs with poor solubility and low permeability. In the present study, a BCS class IV drug and a P-glycoprotein (P-gp) substrate, morin, was selected as the model drug to elucidate the oral absorption mechanism of PLC-SNEDDS. PLC-SNEDDS was superior to PLC in protecting morin from degradation by intestinal enzymes in vitro. In situ perfusion study showed increased intestinal permeability by PLC was duodenum-specific. In contrast, PLC-SNEDDS increased morin permeability in all intestinal segments and induced a change in the main absorption site of morin from colon to ileum. Moreover, ileum conducted the lymphatic transport of PLC-SNEDDS, which was proven by microscopic intestinal visualization of Nile red labeled PLC-SNEDDS and lymph fluids in vivo. Low cytotoxicity and increased Caco-2 cell uptake suggested a safe and efficient delivery of PLC-SNEDDS. The increased membrane fluidity and disrupted actin filaments were closely associated with the increased cell uptake of PLC-SNEDDS. PLC-SNEDDS could be internalized into enterocytes as an intact form in a cholesterol-dependent manner via clathrin-mediated endocytosis and macropinocytosis. The enhanced oral absorption of morin was attributed to the P-gp inhibition by Cremophor RH and the intact internalization of M-PLC-SNEDDS into Caco-2 cells bypassing P-gp recognition. Our findings thus provide new insights into the development of novel nanoemulsions for poorly absorbed drugs.

  9. MALDI imaging facilitates new topical drug development process by determining quantitative skin distribution profiles.

    Science.gov (United States)

    Bonnel, David; Legouffe, Raphaël; Eriksson, André H; Mortensen, Rasmus W; Pamelard, Fabien; Stauber, Jonathan; Nielsen, Kim T

    2018-04-01

    Generation of skin distribution profiles and reliable determination of drug molecule concentration in the target region are crucial during the development process of topical products for treatment of skin diseases like psoriasis and atopic dermatitis. Imaging techniques like mass spectrometric imaging (MSI) offer sufficient spatial resolution to generate meaningful distribution profiles of a drug molecule across a skin section. In this study, we use matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to generate quantitative skin distribution profiles based on tissue extinction coefficient (TEC) determinations of four different molecules in cross sections of human skin explants after topical administration. The four drug molecules: roflumilast, tofacitinib, ruxolitinib, and LEO 29102 have different physicochemical properties. In addition, tofacitinib was administrated in two different formulations. The study reveals that with MALDI-MSI, we were able to observe differences in penetration profiles for both the four drug molecules and the two formulations and thereby demonstrate its applicability as a screening tool when developing a topical drug product. Furthermore, the study reveals that the sensitivity of the MALDI-MSI techniques appears to be inversely correlated to the drug molecules' ability to bind to the surrounding tissues, which can be estimated by their Log D values. Graphical abstract.

  10. Enabling the intestinal absorption of highly polar antiviral agents: ion-pair facilitated membrane permeation of zanamivir heptyl ester and guanidino oseltamivir.

    Science.gov (United States)

    Miller, Jonathan M; Dahan, Arik; Gupta, Deepak; Varghese, Sheeba; Amidon, Gordon L

    2010-08-02

    Antiviral drugs often suffer from poor intestinal permeability, preventing their delivery via the oral route. The goal of this work was to enhance the intestinal absorption of the low-permeability antiviral agents zanamivir heptyl ester (ZHE) and guanidino oseltamivir (GO) utilizing an ion-pairing approach, as a critical step toward making them oral drugs. The counterion 1-hydroxy-2-naphthoic acid (HNAP) was utilized to enhance the lipophilicity and permeability of the highly polar drugs. HNAP substantially increased the log P of the drugs by up to 3.7 log units. Binding constants (K(11(aq))) of 388 M(-1) for ZHE-HNAP and 2.91 M(-1) for GO-HNAP were obtained by applying a quasi-equilibrium transport model to double-reciprocal plots of apparent octanol-buffer distribution coefficients versus HNAP concentration. HNAP enhanced the apparent permeability (P(app)) of both compounds across Caco-2 cell monolayers in a concentration-dependent manner, as substantial P(app) (0.8-3.0 x 10(-6) cm/s) was observed in the presence of 6-24 mM HNAP, whereas no detectable transport was observed without counterion. Consistent with a quasi-equilibrium transport model, a linear relationship with slope near 1 was obtained from a log-log plot of Caco-2 P(app) versus HNAP concentration, supporting the ion-pair mechanism behind the permeability enhancement. In the rat jejunal perfusion assay, the addition of HNAP failed to increase the effective permeability (P(eff)) of GO. However, the rat jejunal permeability of ZHE was significantly enhanced by the addition of HNAP in a concentration-dependent manner, from essentially zero without HNAP to 4.0 x 10(-5) cm/s with 10 mM HNAP, matching the P(eff) of the high-permeability standard metoprolol. The success of ZHE-HNAP was explained by its >100-fold stronger K(11(aq)) versus GO-HNAP, making ZHE-HNAP less prone to dissociation and ion-exchange with competing endogenous anions and able to remain intact during membrane permeation. Overall, this

  11. A Comparative Study of Molecular Structure, pKa, Lipophilicity, Solubility, Absorption and Polar Surface Area of Some Antiplatelet Drugs

    Directory of Open Access Journals (Sweden)

    Milan Remko

    2016-03-01

    Full Text Available Theoretical chemistry methods have been used to study the molecular properties of antiplatelet agents (ticlopidine, clopidogrel, prasugrel, elinogrel, ticagrelor and cangrelor and several thiol-containing active metabolites. The geometries and energies of most stable conformers of these drugs have been computed at the Becke3LYP/6-311++G(d,p level of density functional theory. Computed dissociation constants show that the active metabolites of prodrugs (ticlopidine, clopidogrel and prasugrel and drugs elinogrel and cangrelor are completely ionized at pH 7.4. Both ticagrelor and its active metabolite are present at pH = 7.4 in neutral undissociated form. The thienopyridine prodrugs ticlopidine, clopidogrel and prasugrel are lipophilic and insoluble in water. Their lipophilicity is very high (about 2.5–3.5 logP values. The polar surface area, with regard to the structurally-heterogeneous character of these antiplatelet drugs, is from very large interval of values of 3–255 Å2. Thienopyridine prodrugs, like ticlopidine, clopidogrel and prasugrel, with the lowest polar surface area (PSA values, exhibit the largest absorption. A high value of polar surface area (PSA of cangrelor (255 Å2 results in substantial worsening of the absorption in comparison with thienopyridine drugs.

  12. Specificity of drug transport mediated by CaMDR1: a major facilitator ...

    Indian Academy of Sciences (India)

    Unknown

    CaMDR1 encodes a major facilitator superfamily (MFS) protein in Candida albicans whose expression has been linked to .... by plaque assay and the integration of CaMDR1 at the ... with recombinant virus, vAcCaMDR1 and cells infected.

  13. Drug- and Alcohol-Facilitated, Incapacitated, and Forcible Rape in Relation to Mental Health among a National Sample of Women

    Science.gov (United States)

    Zinzow, Heidi M.; Resnick, Heidi S.; Amstadter, Ananda B.; McCauley, Jenna L.; Ruggiero, Kenneth J.; Kilpatrick, Dean G.

    2009-01-01

    Objective Rape is a well-established risk factor for mental health disorders such as posttraumatic stress disorder (PTSD) and depression. However, most studies have focused on forcible rape tactics and have not distinguished these from tactics that involve drug or alcohol intoxication. Our aim was to examine correlates of PTSD and depression in a community sample of women, with particular emphasis on evaluating the unique effects of lifetime exposure to three specific rape tactics. Methods A nationally representative sample of 3,001 non-institutionalized, civilian, English or Spanish speaking women (aged 18–86 years) participated in a structured telephone interview by use of Computer-Assisted Telephone Interviewing technology. Results Multivariable models showed that history of drug or alcohol facilitated rape tactics (OR = 1.87, prape tactics (OR = 3.46, prape was associated with depression (OR = 3.65, prape tactics were associated with a number of factors that may have contributed to their stronger association with mental health outcomes, including force, injury, lower income, revictimization history, and labeling the event as rape. Conclusions Our results underscore the importance of using a behaviorally specific assessment of rape history, as rape tactic and multiple rape history differentially predicted psychopathology outcomes. The association between drug or alcohol facilitated rape tactics and PTSD suggests that these are important rape tactics to include in assessments and future studies. PMID:20100896

  14. Effects of gastric pH on oral drug absorption: In vitro assessment using a dissolution/permeation system reflecting the gastric dissolution process.

    Science.gov (United States)

    Kataoka, Makoto; Fukahori, Miho; Ikemura, Atsumi; Kubota, Ayaka; Higashino, Haruki; Sakuma, Shinji; Yamashita, Shinji

    2016-04-01

    The aim of the present study was to evaluate the effects of gastric pH on the oral absorption of poorly water-soluble drugs using an in vitro system. A dissolution/permeation system (D/P system) equipped with a Caco-2 cell monolayer was used as the in vitro system to evaluate oral drug absorption, while a small vessel filled with simulated gastric fluid (SGF) was used to reflect the gastric dissolution phase. After applying drugs in their solid forms to SGF, SGF solution containing a 1/100 clinical dose of each drug was mixed with the apical solution of the D/P system, which was changed to fasted state-simulated intestinal fluid. Dissolved and permeated amounts on applied amount of drugs were then monitored for 2h. Similar experiments were performed using the same drugs, but without the gastric phase. Oral absorption with or without the gastric phase was predicted in humans based on the amount of the drug that permeated in the D/P system, assuming that the system without the gastric phase reflected human absorption with an elevated gastric pH. The dissolved amounts of basic drugs with poor water solubility, namely albendazole, dipyridamole, and ketoconazole, in the apical solution and their permeation across a Caco-2 cell monolayer were significantly enhanced when the gastric dissolution process was reflected due to the physicochemical properties of basic drugs. These amounts resulted in the prediction of higher oral absorption with normal gastric pH than with high gastric pH. On the other hand, when diclofenac sodium, the salt form of an acidic drug, was applied to the D/P system with the gastric phase, its dissolved and permeated amounts were significantly lower than those without the gastric phase. However, the oral absorption of diclofenac was predicted to be complete (96-98%) irrespective of gastric pH because the permeated amounts of diclofenac under both conditions were sufficiently high to achieve complete absorption. These estimations of the effects of

  15. Magnetic Nanoparticle Facilitated Drug Delivery for Cancer Therapy with Targeted and Image-Guided Approaches.

    Science.gov (United States)

    Huang, Jing; Li, Yuancheng; Orza, Anamaria; Lu, Qiong; Guo, Peng; Wang, Liya; Yang, Lily; Mao, Hui

    2016-06-14

    With rapid advances in nanomedicine, magnetic nanoparticles (MNPs) have emerged as a promising theranostic tool in biomedical applications, including diagnostic imaging, drug delivery and novel therapeutics. Significant preclinical and clinical research has explored their functionalization, targeted delivery, controllable drug release and image-guided capabilities. To further develop MNPs for theranostic applications and clinical translation in the future, we attempt to provide an overview of the recent advances in the development and application of MNPs for drug delivery, specifically focusing on the topics concerning the importance of biomarker targeting for personalized therapy and the unique magnetic and contrast-enhancing properties of theranostic MNPs that enable image-guided delivery. The common strategies and considerations to produce theranostic MNPs and incorporate payload drugs into MNP carriers are described. The notable examples are presented to demonstrate the advantages of MNPs in specific targeting and delivering under image guidance. Furthermore, current understanding of delivery mechanisms and challenges to achieve efficient therapeutic efficacy or diagnostic capability using MNP-based nanomedicine are discussed.

  16. Emerging integrated nanoclay-facilitated drug delivery system for papillary thyroid cancer therapy

    Science.gov (United States)

    Zhang, Yi; Long, Mei; Huang, Peng; Yang, Huaming; Chang, Shi; Hu, Yuehua; Tang, Aidong; Mao, Linfeng

    2016-09-01

    Nanoclay can be incorporated into emerging dual functional drug delivery systems (DDSs) to promote efficiency in drug delivery and reduce the toxicity of doxorubicin (DOX) used for thyroid cancer treatment. This paper reports the expansion of the basal spacing of kaolinite nanoclay was expanded from 0.72 nm to 0.85 nm, which could provide sufficiently spacious site for hosting doxorubicin molecules and controlling the diffusion rate. A targeted design for papillary thyroid cancer cells was achieved by introducing KI, which is consumed by the sodium-iodide symporter (NIS). As indicated by MTT assays, confocal laser scanning microscopy and bio-TEM observations, methoxy-intercalated kaolinite (KaolinMeOH) exhibited negligible cytotoxicity against papillary thyroid cancer cells. By contrast, DOX-KaolinMeOH showed dose-dependent therapeutic effects in vitro, and KI@DOX-KaolinMeOH was found to act as a powerful targeted therapeutic drug. Furthermore, active and passive targeting strategies played a role in the accumulation of the drug molecules, as verified by an in vivo bio-distribution analysis.

  17. Detection of the antipsychotic drug quetiapine in the blood, urine and hair samples of the victim of a drug-facilitated sexual assault

    DEFF Research Database (Denmark)

    Johansen, Sys Stybe

    2017-01-01

    A drug rape facilitated with the sedative antipsychotic drug quetiapine is presented here. A teenage girl and her girlfriend went to the home of an adult couple they had met at a bar. Here, the teenage girl (victim) felt tired after consuming some alcoholic drinks and fell asleep. While she......-three hours after the suspected drug-facilitated sexual assault (DFSA), blood and urine samples were collected and the initial toxicological screening detected quetiapine. Confirmation and quantification by ultra high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) revealed...... a concentration of 0.007mg/kg quetiapine in blood and 0.19mg/l in urine. Six months after the DFSA, a hair sample was collected and segmental hair analysis was performed on four washed segments (0-3cm, 3-5cm, 5-7cm, and 7-9cm). The last segment contained 0.011ng/mg of quetiapine, whereas the other segments were...

  18. Intestinal absorption of the antiepileptic drug substance vigabatrin is altered by infant formula in vitro and in vivo

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd

    2014-01-01

    Vigabatrin is an antiepileptic drug substance mainly used in pediatric treatment of infantile spasms. The main source of nutrition for infants is breast milk and/or infant formula. Our hypothesis was that infant formula may affect the intestinal absorption of vigabatrin. The aim was therefore...... to investigate the potential effect of coadministration of infant formula with vigabatrin on the oral absorption in vitro and in vivo. The effect of vigabatrin given with an infant formula on the oral uptake and transepithelial transport was investigated in vitro in Caco-2 cells. In vivo effects of infant...... formula and selected amino acids on the pharmacokinetic profile of vigabatrin was investigated after oral coadministration to male Sprague–Dawley rats using acetaminophen as a marker for gastric emptying. The presence of infant formula significantly reduced the uptake rate and permeability of vigabatrin...

  19. Aminoclay–lipid hybrid composite as a novel drug carrier of fenofibrate for the enhancement of drug release and oral absorption

    Directory of Open Access Journals (Sweden)

    Yang L

    2016-03-01

    Full Text Available Liang Yang, Yating Shao, Hyo-Kyung Han BK Plus Project Team, College of Pharmacy, Dongguk University, Goyang, South Korea Abstract: This study aimed to prepare the aminoclay–lipid hybrid composite to enhance the drug release and improve the oral bioavailability of poorly water-soluble fenofibrate. Antisolvent precipitation coupled with an immediate freeze-drying method was adopted to incorporate fenofibrate into aminoclay–lipid hybrid composite (ALC. The optimal composition of the ALC formulation was determined as the ratios of aminoclay to krill oil of 3:1 (w/w, krill oil to fenofibrate of 2:1 (w/w, and antisolvent to solvent of 6:4 (v/v. The morphological characteristics of ALC formulation were determined using scanning electron microscopy, differential scanning calorimetry, and X-ray powder diffraction, which indicated microcrystalline state of fenofibrate in ALC formulation. The ALC formulation achieved almost complete dissolution within 30 minutes, whereas the untreated powder and physical mixture exhibited less than 15% drug release. Furthermore, ALC formulation effectively increased the peak plasma concentration (Cmax and area under the curve (AUC of fenofibric acid (an active metabolite in rats by approximately 13- and seven-fold, respectively. Furthermore, ALC formulation exhibited much lower moisture sorption behavior than the lyophilized formulation using sucrose as a cryoprotectant. Taken together, the present findings suggest that ALC formulation is promising for improving the oral absorption of poorly soluble fenofibrate. Keywords: aminoclay, omega-3 phospholipids, fenofibrate, drug release, oral absorption 

  20. In silico prediction of drug dissolution and absorption with variation in intestinal pH for BCS class II weak acid drugs: ibuprofen and ketoprofen.

    Science.gov (United States)

    Tsume, Yasuhiro; Langguth, Peter; Garcia-Arieta, Alfredo; Amidon, Gordon L

    2012-10-01

    The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS class III and BCS class II have been proposed, in particular, BCS class II weak acids. However, a discrepancy between the in vivo BE results and in vitro dissolution results for BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH of 6.0. Further the experimental dissolution of ibuprofen tablets in a low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol l (-1) /pH) was dramatically reduced compared with the dissolution in SIF (the average buffer capacity 12.6 mmol l (-1) /pH). Thus these predictions for the oral absorption of BCS class II acids indicate that the absorption patterns depend largely on the intestinal pH and buffer strength and must be considered carefully for a bioequivalence test. Simulation software may be a very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard. Copyright © 2012 John Wiley & Sons, Ltd.

  1. In Silico Prediction of Drug Dissolution and Absorption with variation in Intestinal pH for BCS Class II Weak Acid Drugs: Ibuprofen and Ketoprofen§

    Science.gov (United States)

    Tsume, Yasuhiro; Langguth, Peter; Garcia-Arieta, Alfredo; Amidon, Gordon L.

    2012-01-01

    The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS Class III and BCS class II have been proposed, particularly, BCS class II weak acids. However, a discrepancy between the in vivo- BE results and in vitro- dissolution results for a BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH=6.0. Further the experimental dissolution of ibuprofen tablets in the low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol L-1/pH) was dramatically reduced compared to the dissolution in SIF (the average buffer capacity 12.6 mmol L -1/pH). Thus these predictions for oral absorption of BCS class II acids indicate that the absorption patterns largely depend on the intestinal pH and buffer strength and must be carefully considered for a bioequivalence test. Simulation software may be very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard. PMID:22815122

  2. Cognitive Enhancers for Facilitating Drug Cue Extinction: Insights from Animal Models

    OpenAIRE

    Nic Dhonnchadha, Bríd Áine; Kantak, Kathleen M.

    2011-01-01

    Given the success of cue exposure (extinction) therapy combined with a cognitive enhancer for reducing anxiety, it is anticipated that this approach will prove more efficacious than exposure therapy alone in preventing relapse in individuals with substance use disorders. Several factors may undermine the efficacy of exposure therapy for substance use disorders, but we suspect that neurocognitive impairments associated with chronic drug use are an important contributing factor. Numerous insigh...

  3. The contribution of the in-vivo fate of an oil depot to drug absorption

    NARCIS (Netherlands)

    Kalicharan, R. W.; Oussoren, C; Schot, Peter; Rijk, de, E.; Vromans, H.

    2017-01-01

    Sustained release of lipophilic compounds can be achieved with oil depots. These parenteral formulations are generally injected in the vastus lateralis and deltoid muscle. It is known that the absorption rate differs between these two muscles. The reason for this is not fully understood. The aim of

  4. Drug facilitated sexual assault: detection and stability of benzodiazepines in spiked drinks using gas chromatography-mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Lata Gautam

    Full Text Available Benzodiazepines are detected in a significant number of drug facilitated sexual assaults (DFSA. Whilst blood and urine from the victim are routinely analysed, due to the delay in reporting DFSA cases and the short half lives of most of these drugs in blood and urine, drug detection in such samples is problematic. Consideration of the drinks involved and analysis for drugs may start to address this. Here we have reconstructed the 'spiking' of three benzodiazepines (diazepam, flunitrazepam and temazepam into five drinks, an alcopop (flavoured alcoholic drink, a beer, a white wine, a spirit, and a fruit based non-alcoholic drink (J2O chosen as representative of those drinks commonly used by women in 16-24 year old age group. Using a validated GC-MS method for the simultaneous detection of these drugs in the drinks we have studied the storage stability of the benzodiazepines under two different storage conditions, uncontrolled room temperature and refrigerator (4°C over a 25 day period. All drugs could be detected in all beverages over this time period. Diazepam was found to be stable in all of the beverages, except the J2O, under both storage conditions. Flunitrazepam and temazepam were found not to be stable but were detectable (97% loss of temazepam and 39% loss of flunitrazepam from J2O. The recommendations from this study are that there should be a policy change and that drinks thought to be involved in DFSA cases should be collected and analysed wherever possible to support other evidence types.

  5. A magnetic bead-based ligand binding assay to facilitate human kynurenine 3-monooxygenase drug discovery.

    Science.gov (United States)

    Wilson, Kris; Mole, Damian J; Homer, Natalie Z M; Iredale, John P; Auer, Manfred; Webster, Scott P

    2015-02-01

    Human kynurenine 3-monooxygenase (KMO) is emerging as an important drug target enzyme in a number of inflammatory and neurodegenerative disease states. Recombinant protein production of KMO, and therefore discovery of KMO ligands, is challenging due to a large membrane targeting domain at the C-terminus of the enzyme that causes stability, solubility, and purification difficulties. The purpose of our investigation was to develop a suitable screening method for targeting human KMO and other similarly challenging drug targets. Here, we report the development of a magnetic bead-based binding assay using mass spectrometry detection for human KMO protein. The assay incorporates isolation of FLAG-tagged KMO enzyme on protein A magnetic beads. The protein-bound beads are incubated with potential binding compounds before specific cleavage of the protein-compound complexes from the beads. Mass spectrometry analysis is used to identify the compounds that demonstrate specific binding affinity for the target protein. The technique was validated using known inhibitors of KMO. This assay is a robust alternative to traditional ligand-binding assays for challenging protein targets, and it overcomes specific difficulties associated with isolating human KMO. © 2014 Society for Laboratory Automation and Screening.

  6. Variational finite element method to study the absorption rate of drug ...

    African Journals Online (AJOL)

    M.A. Khanday

    2014-11-25

    Nov 25, 2014 ... Abstract Background: The delivery of drugs through dermal layers known as transdermal ... number of factors which includes the physio-co-chemical prop- ..... 9. Kumari B, Adlakha N. One dimensional model to study the effect.

  7. Variational finite element method to study the absorption rate of drug ...

    African Journals Online (AJOL)

    M.A. Khanday

    2014-11-25

    Nov 25, 2014 ... ematical transport models describing the release of drug from various delivery systems and ... numerical simulations to describe the pharmacokinetics of ... studied the diffusion of heat and mass in biological tissues particularly ...

  8. In vivo evaluation of thiolated poly(acrylic acid) as a drug absorption modulator for MRP2 efflux pump substrates.

    Science.gov (United States)

    Greindl, Melanie; Föger, Florian; Hombach, Juliane; Bernkop-Schnürch, Andreas

    2009-08-01

    Recently, several polymers have been reported to modulate drug absorption by inhibition of intestinal efflux pumps such as multidrug resistance proteins (MRPs) and P-glycoprotein (P-gp). The aim of the present study was to evaluate the efficiency of thiolated poly(acrylic acid) (PAA-Cys) to act as a drug absorption modulator for MRP2 efflux pump substrates in vivo, using sulforhodamine 101 as representative MRP2 substrate. In vitro, the permeation-enhancing effect of unmodified PAA and PAA(250)-Cys(,) displaying 580 micromol free thiol groups per gram polymer, was evaluated by using freshly excised rat intestinal mucosa mounted in Ussing-type chambers. In comparison to that of the buffer control, the sulforhodamine 101 transport in the presence of 0.5% unmodified PAA(250) and 0.5% (w/v) PAA(250)-Cys was 1.3- and 4.0-fold improved, respectively. In vivo, sulforhodamine 101 solutions containing 4% (w/v) unmodified PAA(250) or 4% (w/v) thiolated PAA(250) were orally given to rats. The PAA(250)-Cys solution increased the area under the plasma concentration-time curve (AUC(0-12)) of sulforhodamine 101 3.8-fold in comparison to control and 2.2-fold in comparison to unmodified PAA(250). This in vivo study revealed that PAA(250)-Cys significantly increased the oral bioavailability of MRP2 substrate sulforhodamine 101.

  9. Recent Advances in Delivery Systems and Therapeutics of Cinnarizine: A Poorly Water Soluble Drug with Absorption Window in Stomach

    Directory of Open Access Journals (Sweden)

    Smita Raghuvanshi

    2014-01-01

    Full Text Available Low solubility causing low dissolution in gastrointestinal tract is the major problem for drugs meant for systemic action after oral administration, like cinnarizine. Pharmaceutical products of cinnarizine are commercialized globally as immediate release preparations presenting low absorption with low and erratic bioavailability. Approaches to enhance bioavailability are widely cited in the literature. An attempt has been made to review the bioavailability complications and clinical therapeutics of poorly water soluble drug: cinnarizine. The interest of writing this paper is to summarize the pharmacokinetic limitations of drug with special focus on strategies to improvise bioavailability along with effectiveness of novel dosage forms to circumvent the obstacle. The paper provides insight to the approaches to overcome low and erratic bioavailability of cinnarizine by cyclodextrin complexes and novel dosage forms: self-nanoemulsifying systems and buoyant microparticulates. Nanoformulations need to systematically explored in future, for their new clinical role in prophylaxis of migraine attacks in children. Clinical reports have affirmed the role of cinnarizine in migraine prophylaxis. Research needs to be dedicated to develop dosage forms for efficacious bioavailability and drug directly to brain.

  10. Enhancement of in-vitro drug dissolution of ketoconazole for its optimal in-vivo absorption using Nanoparticles and Solid Dispersion forms of the drug

    Science.gov (United States)

    Syed, Mohammed Irfan

    was modified to include 0.02%, 0.05% and 0.1% sodium lauryl sulfate. Here, after 2 hours, the amount of drug dissolved was calculated to be 10% from controls, 21% from solid dispersion and 36% from nanoparticles in SIF with 0.02% SLS. Drug release was 20% from controls, 41% from solid dispersion and 52% from nanoparticle formulation in SIF with 0.05% SLS. Whereas amount of drug released in SIF with 0.1% SLS showed 21% from the control, 62% from solid dispersion and 85% from Nanoparticles respectively. This data supports that the ketoconazole Nanoparticles and its solid-dispersion exhibit many fold increase in dissolution of the drug, which could lead to a less variable and enhanced in-vivo drug absorption profiles. In addition, the data from the Physical Characterization (DSC, XRD and FTIR) supports that there were no interaction within the ingredients occurred in Nanoparticles and solid-dispersion formulations of the drug sample. Wet Bead Milling and Hot Melt methods proved useful in developing the Nanoparticles and solid dispersion form of ketoconazole. Results from particle size analysis were in correlation with data obtained from Scanning electron Microscopy and size of the nanoparticles was below 100nm. The dissolution studies with the modified simulated intestinal fluid (SIF) exhibited several fold increase in the dissolution of the drug compared to the pure drug powder and the commercial products used as the control. Also, the results from the physical characterization studies clearly support the stability of ketoconazole in both of these formulations.

  11. MRP2 mediated drug-drug interaction: indomethacin increases sulfasalazine absorption in the small intestine, potentially decreasing its colonic targeting.

    Science.gov (United States)

    Dahan, Arik; Amidon, Gordon L

    2010-02-15

    We have recently shown that efflux transport, mediated by multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP), is responsible for sulfasalazine low-permeability in the small intestine, thereby enabling its colonic targeting and therapeutic action. The purpose of the present study was to evaluate the potential pharmacokinetic interaction between indomethacin and sulfasalazine, in the mechanism of efflux transporter competition. The concentration-dependent effects of indomethacin on sulfasalazine intestinal epithelial transport were investigated across Caco-2 cell monolayers, in both apical to basolateral (AP-BL) and BL-AP directions. The interaction was then investigated in the in situ single-pass rat jejunal perfusion model. Sulfasalazine displayed 30-fold higher BL-AP than AP-BL Caco-2 permeability, indicative of net mucosal secretion. Indomethacin significantly increased AP-BL and decreased BL-AP sulfasalazine Caco-2 transport, in a concentration-dependent manner, with IC(50) values of 75 and 196 microM respectively. In the rat model, higher sulfasalazine concentrations resulted in higher intestinal permeability, consistent with saturation of efflux transporter. Without indomethacin, sulfasalazine demonstrated low rat jejunal permeability (vs. metoprolol). Indomethacin significantly increased sulfasalazine P(eff), effectively shifting it from BCS (biopharmaceutics classification system) Class IV to II. In conclusion, the data indicate that concomitant intake of indomethacin and sulfasalazine may lead to increased absorption of sulfasalazine in the small intestine, thereby reducing its colonic concentration and potentially altering its therapeutic effect. Copyright 2009 Elsevier B.V. All rights reserved.

  12. Folate absorption

    International Nuclear Information System (INIS)

    Baker, S.J.

    1976-01-01

    Folate is the generic term given to numerous compounds of pteroic acid with glutamic acid. Knowledge of absorption is limited because of the complexities introduced by the variety of compounds and because of the inadequacy of investigational methods. Two assay methods are in use, namely microbiological and radioactive. Techniques used to study absorption include measurement of urinary excretion, serum concentration, faecal excretion, intestinal perfusion, and haematological response. It is probably necessary to test absorption of both pteroylmonoglutamic acid and one or more polyglutamates, and such tests would be facilitated by availability of synthesized compounds labelled with radioactive tracers at specifically selected sites. (author)

  13. Impact of concentration and rate of intraluminal drug delivery on absorption and gut wall metabolism of verapamil in humans.

    Science.gov (United States)

    Glaeser, Hartmut; Drescher, Siegfried; Hofmann, Ute; Heinkele, Georg; Somogyi, Andrew A; Eichelbaum, Michel; Fromm, Martin F

    2004-09-01

    In humans gut wall metabolism can be quantitatively as important as hepatic drug metabolism in limiting the systemic exposure to drugs after oral administration. However, it has been proposed that the role of gut wall metabolism might be overemphasized, because high luminal drug concentrations would lead to a saturation of gut wall metabolism. Therefore we investigated the impact of concentration and rate of intraluminal drug delivery on absorption (F(abs)) and gastrointestinal extraction (E(GI)) of a luminally administered cytochrome P450 (CYP) 3A4 substrate (verapamil) using a multilumen perfusion catheter in combination with a stable isotope technique. Two 20-cm-long, adjacent jejunal segments were isolated with the multilumen perfusion catheter in 7 subjects. In this study 80 mg of unlabeled verapamil (d0-verapamil 15 min) was infused into one segment over a 15-minute period, 80 mg of 3-fold deuterated verapamil (d3-verapamil 240 min) was administered over a 240-minute period into the other segment, and simultaneously, 5 mg of 7-fold deuterated verapamil (d7-verapamil) was injected intravenously over a 15-minute period. The rate of intraluminal drug delivery had only a modest effect on bioavailability of the verapamil isotopes (after correction for F abs ) (F/F abs d3-verapamil 240 min versus d0-verapamil 15 min, 0.24 +/- 0.10 versus 0.20 +/- 0.09; P d3-verapamil 240 min was 0.50 +/- 0.18 compared with 0.59 +/- 0.14 for d0 -verapamil 15 min ( P d0-verapamil 15 min ) correlated strongly with E GI (d3-verapamil 240 min ) (r = 0.94, P d0-verapamil 15 min /d3-verapamil 240 min (r = 0.62, P =.03). Substantial gut wall metabolism of verapamil occurs in humans and can be predicted from ex vivo data by use of shed enterocytes. The different intraluminal concentrations and rates of intraluminal drug delivery did not lead to a pronounced saturation of intestinal drug metabolism.

  14. Microbiome-mediated bile acid modification: Role in intestinal drug absorption and metabolism.

    Science.gov (United States)

    Enright, Elaine F; Griffin, Brendan T; Gahan, Cormac G M; Joyce, Susan A

    2018-04-13

    Once regarded obscure and underappreciated, the gut microbiota (the microbial communities colonizing the gastrointestinal tract) is gaining recognition as an influencer of many aspects of human health. Also increasingly apparent is the breadth of interindividual variation in these co-evolved microbial-gut associations, presenting novel quests to explore implications for disease and therapeutic response. In this respect, the unearthing of the drug-metabolizing capacity of the microbiota has provided impetus for the integration of microbiological and pharmacological research. This review considers a potential mechanism, 'microbial bile acid metabolism', by which the intricate interplay between the host and gut bacteria may influence drug pharmacokinetics. Bile salts traditionally regarded as biological surfactants, synthesized by the host and biotransformed by gut bacteria, are now also recognized as signalling molecules that affect diverse physiological processes. Accumulating data indicate that bile salts are not equivalent with respect to their physicochemical properties, micellar solubilization capacities for poorly water-soluble drugs, crystallization inhibition tendencies nor potencies for bile acid receptor activation. Herein, the origin, physicochemical properties, physiological functions, plasticity and pharmaceutical significance of the human bile acid pool are discussed. Microbial dependant differences in the composition of the human bile acid pool, simulated intestinal media and commonly used preclinical species is highlighted to better understand in vivo performance predictiveness. While the precise impact of an altered gut microbiome, and consequently bile acid pool, in the biopharmaceutical setting remains largely elusive, the objective of this article is to aid knowledge acquisition through a detailed review of the literature. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. In silico and in vitro prediction of gastrointestinal absorption from potential drug eremantholide C.

    Science.gov (United States)

    Caldeira, Tamires G; Saúde-Guimarães, Dênia A; Dezani, André B; Serra, Cristina Helena Dos Reis; de Souza, Jacqueline

    2017-11-01

    Analysis of the biopharmaceutical properties of eremantholide C, sesquiterpene lactone with proven pharmacological activity and low toxicity, is required to evaluate its potential to become a drug. Preliminary analysis of the physicochemical characteristics of eremantholide C was performed in silico. Equilibrium solubility was evaluated using the shake-flask method, at 37.0 °C, 100 rpm during 72 h in biorelevant media. The permeability was analysed using parallel artificial membrane permeability assay, at 37.0 °C, 50 rpm for 5 h. The donor compartment was composed of an eremantholide C solution in intestinal fluid simulated without enzymes, while the acceptor compartment consisted of phosphate buffer. Physicochemical characteristics predicted in silico indicated that eremantholide C has a low solubility and high permeability. In-vitro data of eremantholide C showed low solubility, with values for the dose/solubility ratio (ml): 9448.82, 10 389.61 e 15 000.00 for buffers acetate (pH 4.5), intestinal fluid simulated without enzymes (pH 6.8) and phosphate (pH 7.4), respectively. Also, it showed high permeability, with effective permeability of 30.4 × 10 -6 cm/s, a higher result compared with propranolol hydrochloride (9.23 × 10 -6 cm/s). The high permeability combined with its solubility, pharmacological activity and low toxicity demonstrate the importance of eremantholide C as a potential drug candidate. © 2017 Royal Pharmaceutical Society.

  16. Microneedles as Enhancer of Drug Absorption Through the Skin and Applications in Medicine and Cosmetology.

    Science.gov (United States)

    Serrano-Castañeda, Pablo; Escobar-Chavez, Jose Juan; Rodriguez-Cruz, Isabel Marlen; Melgoza, Luz Maria; Martinez-Hernandez, Jessica

    2018-01-01

    The microneedles technology has found applications in many health-related fields. For example, their application in drugs and vaccines delivery as well, as the determination of biomarkers, has been reported. They also have a place in the dermatology and cosmetic areas such as the treatment of wounds from burns, scars, acne, depigmentation, and alopecia will be shown. Microneedles are used in therapeutic applications and are manufactured using materials such as metal (steel, titanium, nickel), polymer (oly-glycolic acid (PGA), poly-lactide-co-glycolide acid (PLGA), poly-L-lactic acid (PLA), chitosan), glass, silicon, ceramic, carbohydrates (trehalose, sucrose, mannitol). Examples of application of microneedles and their advantages and disadvantages are discussed. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  17. Correlation between octanol/water and liposome/water distribution coefficients and drug absorption of a set of pharmacologically active compounds.

    Science.gov (United States)

    Esteves, Freddy; Moutinho, Carla; Matos, Carla

    2013-06-01

    Absorption and consequent therapeutic action are key issues in the development of new drugs by the pharmaceutical industry. In this sense, different models can be used to simulate biological membranes to predict the absorption of a drug. This work compared the octanol/water and the liposome/water models. The parameters used to relate the two models were the distribution coefficients between liposomes and water and octanol and water and the fraction of drug orally absorbed. For this study, 66 drugs were collected from literature sources and divided into four groups according to charge and ionization degree: neutral; positively charged; negatively charged; and partially ionized/zwitterionic. The results show a satisfactory linear correlation between the octanol and liposome systems for the neutral (R²= 0.9324) and partially ionized compounds (R²= 0.9367), contrary to the positive (R²= 0.4684) and negatively charged compounds (R²= 0.1487). In the case of neutral drugs, results were similar in both models because of the high fraction orally absorbed. However, for the charged drugs (positively, negatively, and partially ionized/zwitterionic), the liposomal model has a more-appropriate correlation with absorption than the octanol model. These results show that the neutral compounds only interact with membranes through hydrophobic bonds, whereas charged drugs favor electrostatic interactions established with the liposomes. With this work, we concluded that liposomes may be a more-appropriate biomembrane model than octanol for charged compounds.

  18. Potential drug – nanosensor conjugates: Raman, infrared absorption, surface – enhanced Raman, and density functional theory investigations of indolic molecules

    Energy Technology Data Exchange (ETDEWEB)

    Pięta, Ewa, E-mail: Ewa.Pieta@ifj.edu.pl [Institute of Nuclear Physics, Polish Academy of Sciences, PL-31342 Krakow (Poland); Paluszkiewicz, Czesława [Institute of Nuclear Physics, Polish Academy of Sciences, PL-31342 Krakow (Poland); Oćwieja, Magdalena [J. Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, PL-30239 Krakow (Poland); Kwiatek, Wojciech M. [Institute of Nuclear Physics, Polish Academy of Sciences, PL-31342 Krakow (Poland)

    2017-05-15

    Highlights: • Molecular fragments involved in the adsorption process were determined. • Formation of hydrogen bonds with the negatively charged gold substrates was observed. • Indole moiety strongly interacts with gold nanosensors. • The synthesized sensors are characterized by high stability and reproducibility. • Chemical mechanism plays a crucial role in the enhancement of the Raman signal. - Abstract: An extremely important aspect of planning cancer treatment is not only the drug efficiency but also a number of challenges associated with the side effects and control of this process. That is why it is worth paying attention to the promising potential of the gold nanoparticles combined with a compound treated as a potential drug. This work presents Raman (RS), infrared absorption (IR) and surface–enhanced Raman scattering (SERS) spectroscopic investigations of N–acetyl–5–methoxytryptamine (melatonin) and α–methyl–DL–tryptophan, regarding as anti breast cancer agents. The experimental spectroscopic analysis was supported by the quantum-chemical calculations based on the B3LYP hybrid density functional theory (DFT) at the B3LYP 6–311G(d,p) level of theory. The studied compounds were adsorbed onto two colloidal gold nanosensors synthesized by a chemical reduction method using sodium borohydride (SB) and trisodium citrate (TC), respectively. Its morphology characteristics were obtained using transmission electron microscopy (TEM). It has been suggested that the NH moiety from the aromatic ring, a well-known proton donor, causes the formation of hydrogen bonds with the negatively charged gold surface.

  19. Drug Delivery and Transport into the Central Circulation: An Example of Zero-Order In vivo Absorption of Rotigotine from a Transdermal Patch Formulation.

    Science.gov (United States)

    Cawello, Willi; Braun, Marina; Andreas, Jens-Otto

    2018-01-13

    Pharmacokinetic studies using deconvolution methods and non-compartmental analysis to model clinical absorption of drugs are not well represented in the literature. The purpose of this research was (1) to define the system of equations for description of rotigotine (a dopamine receptor agonist delivered via a transdermal patch) absorption based on a pharmacokinetic model and (2) to describe the kinetics of rotigotine disposition after single and multiple dosing. The kinetics of drug disposition was evaluated based on rotigotine plasma concentration data from three phase 1 trials. In two trials, rotigotine was administered via a single patch over 24 h in healthy subjects. In a third trial, rotigotine was administered once daily over 1 month in subjects with early-stage Parkinson's disease (PD). A pharmacokinetic model utilizing deconvolution methods was developed to describe the relationship between drug release from the patch and plasma concentrations. Plasma-concentration over time profiles were modeled based on a one-compartment model with a time lag, a zero-order input (describing a constant absorption via skin into central circulation) and first-order elimination. Corresponding mathematical models for single- and multiple-dose administration were developed. After single-dose administration of rotigotine patches (using 2, 4 or 8 mg/day) in healthy subjects, a constant in vivo absorption was present after a minor time lag (2-3 h). On days 27 and 30 of the multiple-dose study in patients with PD, absorption was constant during patch-on periods and resembled zero-order kinetics. Deconvolution based on rotigotine pharmacokinetic profiles after single- or multiple-dose administration of the once-daily patch demonstrated that in vivo absorption of rotigotine showed constant input through the skin into the central circulation (resembling zero-order kinetics). Continuous absorption through the skin is a basis for stable drug exposure.

  20. Polymeric nanoparticles for increased oral bioavailability and rapid absorption using celecoxib as a model of a low-solubility, high-permeability drug.

    Science.gov (United States)

    Morgen, Michael; Bloom, Corey; Beyerinck, Ron; Bello, Akintunde; Song, Wei; Wilkinson, Karen; Steenwyk, Rick; Shamblin, Sheri

    2012-02-01

    To demonstrate drug/polymer nanoparticles can increase the rate and extent of oral absorption of a low-solubility, high-permeability drug. Amorphous drug/polymer nanoparticles containing celecoxib were prepared using ethyl cellulose and either sodium caseinate or bile salt. Nanoparticles were characterized using dynamic light scattering, transmission and scanning electron microscopy, and differential scanning calorimetry. Drug release and resuspension studies were performed using high-performance liquid chromatography. Pharmacokinetic studies were performed in dogs and humans. A physical model is presented describing the nanoparticle state of matter and release performance. Nanoparticles dosed orally in aqueous suspensions provided higher systemic exposure and faster attainment of peak plasma concentrations than commercial capsules, with median time to maximum drug concentration (Tmax) of 0.75 h in humans for nanoparticles vs. 3 h for commercial capsules. Nanoparticles released celecoxib rapidly and provided higher dissolved-drug concentrations than micronized crystalline drug. Nanoparticle suspensions are stable for several days and can be spray-dried to form dry powders that resuspend in water. Drug/polymer nanoparticles are well suited for providing rapid oral absorption and increased bioavailability of BCS Class II drugs.

  1. Evaluation of the use of Göttingen minipigs to predict food effects on the oral absorption of drugs in humans

    DEFF Research Database (Denmark)

    Christiansen, Martin Lau; Müllertz, Anette; Garmer, Mats

    2015-01-01

    This study investigated the oral absorption of drugs in minipigs to predict food effects in man. The protocol was based on a previously described model in dogs and further investigated the food source (i.e., US FDA breakfast or a nutritional drink) and food quantities. Two poorly soluble compounds...

  2. Investigation of the effect of solubility increase at the main absorption site on bioavailability of BCS class II drug (risperidone) using liquisolid technique.

    Science.gov (United States)

    Khames, Ahmed

    2017-11-01

    BCS class II drugs usually suffer inadequate bioavailability as dissolution step is the absorption rate limiting step. In this work, the effect of solubility increase at the main absorption site for these drugs was investigated using risperidone as a drug model. Liquisolid technique was applied to prepare risperidone per-oral tablets of high dissolution rate at intestinal pH (6.8) using versatile nonionic surfactants of high solubilizing ability [Transcutol HP, Labrasol and Labrasol/Labrafil (1:1) mixture] as liquid vehicles at different drug concentrations (10-30%) and fixed (R). The prepared liquisolid tablets were fully evaluated and the dissolution rate at pH 6.8 was investigated. The formulae that showed significantly different release rate were selected and subjected to mathematical modeling using DE 25 , MDT and similarity factor (f2). Depending on mathematical modeling results, formula of higher dissolution rate was subjected to solid state characterization using differential scanning calorimetric (DSC), infrared spectroscopy (IR) and X-ray diffraction (XRD). Finally, the drug bioavailability was studied in comparison to conventional tablets in rabbits. Results showed that liquisolid tablet prepared using Labrasol/Labrafil (1:1) mixture as liquid vehicle containing 10% risperidone is a compatible formula with law drug crystallinity and higher dissolution rate (100% in 25 min). The drug bioavailability was significantly increased in comparison to the conventional tablets (1441.711 μg h/mL and 137.518 μg/mL in comparison to 321.011 μg h/mL and 38.673 μg/mL for AUC and Cp max , respectively). This led to the conclusion that liquisolid technique was efficiently improved drug solubility and solubility increase of BCS class II drugs at their main absorption site significantly increases their bioavailability.

  3. Curcumin-carboxymethyl chitosan (CNC) conjugate and CNC/LHR mixed polymeric micelles as new approaches to improve the oral absorption of P-gp substrate drugs.

    Science.gov (United States)

    Ni, Jiang; Tian, Fengchun; Dahmani, Fatima Zohra; Yang, Hui; Yue, Deren; He, Shuwang; Zhou, Jianping; Yao, Jing

    2016-11-01

    The low oral bioavailability of numerous drugs has been mostly attributed to the significant effect of P-gp-mediated efflux on intestinal drug transport. Herein, we developed mixed polymeric micelles (MPMs) comprised of curcumin-carboxymethyl chitosan (CNC) conjugate, as a potential inhibitor of P-gp-mediated efflux and gastrointestinal absorption enhancer, and low-molecular-weight heparin-all-trans-retinoid acid (LHR) conjugate, as loading material, with the aim to improve the oral absorption of P-gp substrate drugs. CNC conjugate was synthesized by chemical bonding of curcumin (Cur) and carboxymethyl chitosan (CMCS) taking advantage of the inhibition of intestinal P-gp-mediated secretion by Cur and the intestinal absorption enhancement by CMCS. The chemical structure of CNC conjugate was characterized by 1 H NMR with a degree of substitution of Cur of 4.52-10.20%. More importantly, CNC conjugate markedly improved the stability of Cur in physiological pH. Cyclosporine A-loaded CNC/LHR MPMs (CsA-CNC/LHR MPMs) were prepared by dialysis method, with high drug loading 25.45% and nanoscaled particle size (∼200 nm). In situ single-pass perfusion studies in rats showed that both CsA + CNC mixture and CsA-CNC/LHR MPMs achieved significantly higher K a and P eff than CsA suspension in the duodenum and jejunum segments (p CNC mixture and CsA-CNC/LHR MPMs significantly increased the oral bioavailability of CsA as compared to CsA suspension. These results suggest that CNC conjugate might be considered as a promising gastrointestinal absorption enhancer, while CNC/LHR MPMs had the potential to improve the oral absorption of P-gp substrate drugs.

  4. Quantification of the fluorine containing drug 5-fluorouracil in cancer cells by GaF molecular absorption via high-resolution continuum source molecular absorption spectrometry

    International Nuclear Information System (INIS)

    Krüger, Magnus; Huang, Mao-Dong; Becker-Roß, Helmut; Florek, Stefan; Ott, Ingo; Gust, Ronald

    2012-01-01

    The development of high-resolution continuum source molecular absorption spectrometry made the quantification of fluorine feasible by measuring the molecular absorption as gallium monofluoride (GaF). Using this new technique, we developed on the example of 5-fluorouracil (5-FU) a graphite furnace method to quantify fluorine in organic molecules. The effect of 5-FU on the generation of the diatomic GaF molecule was investigated. The experimental conditions such as gallium nitrate amount, temperature program, interfering anions (represented as corresponding acids) and calibration for the determination of 5-FU in standard solution and in cellular matrix samples were investigated and optimized. The sample matrix showed no effect on the sensitivity of GaF molecular absorption. A simple calibration curve using an inorganic sodium fluoride solution can conveniently be used for the calibration. The described method is sensitive and the achievable limit of detection is 0.23 ng of 5-FU. In order to establish the concept of “fluorine as a probe in medicinal chemistry” an exemplary application was selected, in which the developed method was successfully demonstrated by performing cellular uptake studies of the 5-FU in human colon carcinoma cells. - Highlights: ► Development of HR-CS MAS for quantification of fluorine bound to organic molecules ► Measuring as molecular absorption of gallium monofluoride ► Quantification of organic-bound fluorine in biological material ► The concept of “fluorine as a probe in medicinal chemistry” could be established

  5. Quantification of the fluorine containing drug 5-fluorouracil in cancer cells by GaF molecular absorption via high-resolution continuum source molecular absorption spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Krueger, Magnus [Freie Universitaet Berlin, Institut fuer Pharmazie, Pharmazeutische Chemie, Koenigin-Luise-Str. 2-4, 14195 Berlin (Germany); Huang, Mao-Dong; Becker-Ross, Helmut; Florek, Stefan [Leibniz Institut fuer Analytische Wissenschaften, ISAS-e.V., Department Berlin, Albert-Einstein-Str. 9, 12489 Berlin (Germany); Ott, Ingo [Technische Universitaet Carolo Wilhelmina zu Braunschweig, Institut fuer Medizinische und Pharmazeutische Chemie, Beethovenstr. 55, 38106 Braunschweig (Germany); Gust, Ronald, E-mail: ronald.gust@uibk.ac.at [Universitaet Innsbruck, Institut fuer Pharmazie, Pharmazeutische Chemie, Innrain 80/82, 6020 Innsbruck (Austria)

    2012-03-15

    The development of high-resolution continuum source molecular absorption spectrometry made the quantification of fluorine feasible by measuring the molecular absorption as gallium monofluoride (GaF). Using this new technique, we developed on the example of 5-fluorouracil (5-FU) a graphite furnace method to quantify fluorine in organic molecules. The effect of 5-FU on the generation of the diatomic GaF molecule was investigated. The experimental conditions such as gallium nitrate amount, temperature program, interfering anions (represented as corresponding acids) and calibration for the determination of 5-FU in standard solution and in cellular matrix samples were investigated and optimized. The sample matrix showed no effect on the sensitivity of GaF molecular absorption. A simple calibration curve using an inorganic sodium fluoride solution can conveniently be used for the calibration. The described method is sensitive and the achievable limit of detection is 0.23 ng of 5-FU. In order to establish the concept of 'fluorine as a probe in medicinal chemistry' an exemplary application was selected, in which the developed method was successfully demonstrated by performing cellular uptake studies of the 5-FU in human colon carcinoma cells. - Highlights: Black-Right-Pointing-Pointer Development of HR-CS MAS for quantification of fluorine bound to organic molecules Black-Right-Pointing-Pointer Measuring as molecular absorption of gallium monofluoride Black-Right-Pointing-Pointer Quantification of organic-bound fluorine in biological material Black-Right-Pointing-Pointer The concept of 'fluorine as a probe in medicinal chemistry' could be established.

  6. Quantification of the fluorine containing drug 5-fluorouracil in cancer cells by GaF molecular absorption via high-resolution continuum source molecular absorption spectrometry

    Science.gov (United States)

    Krüger, Magnus; Huang, Mao-Dong; Becker-Roß, Helmut; Florek, Stefan; Ott, Ingo; Gust, Ronald

    The development of high-resolution continuum source molecular absorption spectrometry made the quantification of fluorine feasible by measuring the molecular absorption as gallium monofluoride (GaF). Using this new technique, we developed on the example of 5-fluorouracil (5-FU) a graphite furnace method to quantify fluorine in organic molecules. The effect of 5-FU on the generation of the diatomic GaF molecule was investigated. The experimental conditions such as gallium nitrate amount, temperature program, interfering anions (represented as corresponding acids) and calibration for the determination of 5-FU in standard solution and in cellular matrix samples were investigated and optimized. The sample matrix showed no effect on the sensitivity of GaF molecular absorption. A simple calibration curve using an inorganic sodium fluoride solution can conveniently be used for the calibration. The described method is sensitive and the achievable limit of detection is 0.23 ng of 5-FU. In order to establish the concept of "fluorine as a probe in medicinal chemistry" an exemplary application was selected, in which the developed method was successfully demonstrated by performing cellular uptake studies of the 5-FU in human colon carcinoma cells.

  7. Impaired drug absorption due to high stomach pH: a review of strategies for mitigation of such effect to enable pharmaceutical product development.

    Science.gov (United States)

    Mitra, Amitava; Kesisoglou, Filippos

    2013-11-04

    Published reports have clearly shown that weakly basic drugs which have low solubility at high pH could have impaired absorption in patients with high gastric pH thus leading to reduced and variable bioavailability. Since such reduction in exposure can lead to significant loss of efficacy, it is imperative to (1) understand the behavior of the compound as a function of stomach pH to inform of any risk of bioavailability loss in clinical studies and (2) develop a robust formulation which can provide adequate exposure in achlorhydric patients. In this review paper, we provide an overview of the factors that can cause high gastric pH in human, discuss clinical and preclinical pharmacokinetic data for weak bases under conditions of normal and high gastric pH, and give examples of formulation strategies to minimize or mitigate the reduced absorption of weakly basic drugs under high gastric pH conditions. It should be noted that the ability to overcome pH sensitivity issues is highly compound dependent and there are no obvious and general solutions to overcome such effect. Further, we discuss, along with several examples, the use of biopharmaceutical tools such as in vitro dissolution, absorption modeling, and gastric pH modified animal models to assess absorption risk of weak bases in high gastric pH and also the use of these tools to enable development of formulations to mitigate such effects.

  8. A new concept of efficient therapeutic drug monitoring using the high-resolution continuum source absorption spectrometry and the surface enhanced Raman spectroscopy

    Science.gov (United States)

    Xing, Yanlong; Fuss, Harald; Lademann, Jürgen; Huang, Mao Dong; Becker-Ross, Helmut; Florek, Stefan; Patzelt, Alexa; Meinke, Martina C.; Jung, Sora; Esser, Norbert

    2018-04-01

    In this study, a new therapeutic drug monitoring approach has been tested based on the combination of CaF molecular absorption using high-resolution continuum source absorption spectrometry (HR-CSAS) and surface enhanced Raman spectroscopy (SERS). HR-CSAS with mini graphite tube was successfully tested for clinical therapeutic drug monitoring of the fluorine-containing drug capecitabine in sweat samples of cancer patients: It showed advantageous features of high selectivity (no interference from Cl), high sensitivity (characteristic mass of 0.1 ng at CaF 583.069 nm), low sample consumption (down to 30 nL) and fast measurement (no sample pretreatment and less than 1 min of responding time) in tracing the fluorine signal out of capecitabine. However, this technique has the disadvantage of the total loss of the drug's structure information after burning the sample at very high temperature. Therefore, a new concept of combining HR-CSAS with a non-destructive spectroscopic method (SERS) was proposed for the sensitive sensing and specific identification of capecitabine. We tested and succeed in obtaining the molecular characteristics of the metabolite of capecitabine (named 5-fluorouracil) by the non-destructive SERS technique. With the results shown in this work, it is demonstrated that the combined spectroscopic technique of HR-CSAS and SERS will be very useful in efficient therapeutic drug monitoring in the future.

  9. Barriers and facilitators to disease-modifying antirheumatic drug use in patients with inflammatory rheumatic diseases: a qualitative theory-based study.

    Science.gov (United States)

    Voshaar, Marieke; Vriezekolk, Johanna; van Dulmen, Sandra; van den Bemt, Bart; van de Laar, Mart

    2016-10-21

    Although disease-modifying anti-rheumatic drugs (DMARDs) are the cornerstone of treatment for inflammatory rheumatic diseases, medication adherence to DMARDs is often suboptimal. Effective interventions to improve adherence to DMARDs are lacking, and new targets are needed to improve adherence. The aim of the present study was to explore patients' barriers and facilitators of optimal DMARD use. These factors might be used as targets for adherence interventions. In a mixed method study design, patients (n = 120) with inflammatory arthritis (IA) completed a questionnaire based on an existing adapted Theoretical Domains Framework (TDF) to identify facilitators and barriers of DMARD use. A subgroup of these patients (n = 21) participated in focus groups to provide insights into their facilitators and barriers. The answers to the questionnaires and responses of the focus groups were thematically coded by three researchers independently and subsequently categorized. The barriers and facilitators that were reported by IA patients presented large inter-individual variations. The identified barriers and facilitators could be captured in the following domains based on an adapted TDF: (i) knowledge, (ii) emotions, (iii) attention, memory, and decision processes, (iv) social influences, (v) beliefs about capability, (vi) beliefs about consequences, (vii) motivation and goals, (viii) goal conflict, (ix) environmental context and resources, and (x) skills. Patients with IA have a variety of barriers and facilitators with regard to their DMARD use. All of these barriers and facilitators could be categorized into adapted domains of the TDF. Interventions that address individual facilitators and barriers, based on capability, opportunity, and motivation, are needed to develop strategies for medication adherence that are tailored to individual patient needs.

  10. Macromolecular bipill of gemcitabine and methotrexate facilitates tumor-specific dual drug therapy with higher benefit-to-risk ratio

    DEFF Research Database (Denmark)

    Das, Manasmita; Jain, Roopal; Agrawal, Ashish Kumar

    2014-01-01

    -PEG-MTX conjugate over all other pharmaceutical preparations including free drugs, physical mixture of GEM and MTX, and PEGylated GEM/MTX. Toxicity studies in tumor bearing rats as well as healthy mice corroborated that dual drug conjugation is an effective means to synergize the therapeutic indices of potential...

  11. The impact of supersaturation level for oral absorption of BCS class IIb drugs, dipyridamole and ketoconazole, using in vivo predictive dissolution system: Gastrointestinal Simulator (GIS).

    Science.gov (United States)

    Tsume, Yasuhiro; Matsui, Kazuki; Searls, Amanda L; Takeuchi, Susumu; Amidon, Gregory E; Sun, Duxin; Amidon, Gordon L

    2017-05-01

    The development of formulations and the assessment of oral drug absorption for Biopharmaceutical Classification System (BCS) class IIb drugs is often a difficult issue due to the potential for supersaturation and precipitation in the gastrointestinal (GI) tract. The physiological environment in the GI tract largely influences in vivo drug dissolution rates of those drugs. Thus, those physiological factors should be incorporated into the in vitro system to better assess in vivo performance of BCS class IIb drugs. In order to predict oral bioperformance, an in vitro dissolution system with multiple compartments incorporating physiologically relevant factors would be expected to more accurately predict in vivo phenomena than a one-compartment dissolution system like USP Apparatus 2 because, for example, the pH change occurring in the human GI tract can be better replicated in a multi-compartmental platform. The Gastrointestinal Simulator (GIS) consists of three compartments, the gastric, duodenal and jejunal chambers, and is a practical in vitro dissolution apparatus to predict in vivo dissolution for oral dosage forms. This system can demonstrate supersaturation and precipitation and, therefore, has the potential to predict in vivo bioperformance of oral dosage forms where this phenomenon may occur. In this report, in vitro studies were performed with dipyridamole and ketoconazole to evaluate the precipitation rates and the relationship between the supersaturation levels and oral absorption of BCS class II weak base drugs. To evaluate the impact of observed supersaturation levels on oral absorption, a study utilizing the GIS in combination with mouse intestinal infusion was conducted. Supersaturation levels observed in the GIS enhanced dipyridamole and ketoconazole absorption in mouse, and a good correlation between their supersaturation levels and their concentration in plasma was observed. The GIS, therefore, appears to represent in vivo dissolution phenomena and

  12. Expression Profile of Drug and Nutrient Absorption Related Genes in Madin-Darby Canine Kidney (MDCK Cells Grown under Differentiation Conditions

    Directory of Open Access Journals (Sweden)

    Balvinder S. Vig

    2012-06-01

    Full Text Available The expression levels of genes involved in drug and nutrient absorption were evaluated in the Madin-Darby Canine Kidney (MDCK in vitro drug absorption model. MDCK cells were grown on plastic surfaces (for 3 days or on Transwell® membranes (for 3, 5, 7, and 9 days. The expression profile of genes including ABC transporters, SLC transporters, and cytochrome P450 (CYP enzymes was determined using the Affymetrix® Canine GeneChip®. Expression of genes whose probe sets passed a stringent confirmation process was examined. Expression of a few transporter (MDR1, PEPT1 and PEPT2 genes in MDCK cells was confirmed by RT-PCR. The overall gene expression profile was strongly influenced by the type of support the cells were grown on. After 3 days of growth, expression of 28% of the genes was statistically different (1.5-fold cutoff, p < 0.05 between the cells grown on plastic and Transwell® membranes. When cells were differentiated on Transwell® membranes, large changes in gene expression profile were observed during the early stages, which then stabilized after 5–7 days. Only a small number of genes encoding drug absorption related SLC, ABC, and CYP were detected in MDCK cells, and most of them exhibited low hybridization signals. Results from this study provide valuable reference information on endogenous gene expression in MDCK cells that could assist in design of drug-transporter and/or drug-enzyme interaction studies, and help interpret the contributions of various transporters and metabolic enzymes in studies with MDCK cells.

  13. Flow analysis-hydride generation-gas phase derivative molecular absorption spectrophotometric determination of antimony in antileishmanial drugs

    Directory of Open Access Journals (Sweden)

    Máximo Gallignani

    2009-01-01

    Full Text Available In the present work, the development of a method based on the coupling of flow analysis (FA, hydride generation (HG, and derivative molecular absorption spectrophotometry (D-EAM in gas phase (GP, is described in order to determine total antimony in antileishmanial products. Second derivative order (D²224nm of the absorption spectrum (190 - 300 nm is utilized as measurement criterion. Each one of the parameters involved in the development of the proposed method was examined and optimized. The utilization of the EAM in GP as detection system in a continuous mode instead of atomic absorption spectrometry represents the great potential of the analytic proposal.

  14. Risk assessment of excess drug and sunscreen absorption via skin with ablative fractional laser resurfacing : optimization of the applied dose for postoperative care.

    Science.gov (United States)

    Chen, Wei-Yu; Fang, Chia-Lang; Al-Suwayeh, Saleh A; Yang, Hung-Hsu; Li, Yi-Ching; Fang, Jia-You

    2013-09-01

    The ablative fractional laser is a new modality used for surgical resurfacing. It is expected that laser treatment can generally deliver drugs into and across the skin, which is toxicologically relevant. The aim of this study was to establish skin absorption characteristics of antibiotics, sunscreens, and macromolecules via laser-treated skin and during postoperative periods. Nude mice were employed as the animal model. The skin received a single irradiation of a fractional CO2 laser, using fluences of 4-10 mJ with spot densities of 100-400 spots/cm(2). In vitro skin permeation using Franz cells was performed. Levels of skin water loss and erythema were evaluated, and histological examinations with staining by hematoxylin and eosin, cyclooxygenase-2, and claudin-1 were carried out. Significant signs of erythema, edema, and scaling of the skin treated with the fractional laser were evident. Inflammatory infiltration and a reduction in tight junctions were also observed. Laser treatment at 6 mJ increased tetracycline and tretinoin fluxes by 70- and 9-fold, respectively. A higher fluence resulted in a greater tetracycline flux, but lower skin deposition. On the other hand, tretinoin skin deposition increased following an increase in the laser fluence. The fractional laser exhibited a negligible effect on modulating oxybenzone absorption. Dextrans with molecular weights of 4 and 10 kDa showed increased fluxes from 0.05 to 11.05 and 38.54 μg/cm(2)/h, respectively. The optimized drug dose for skin treated with the fractional laser was 1/70-1/60 of the regular dose. The skin histology and drug absorption had recovered to a normal status within 2-3 days. Our findings provide the first report on risk assessment of excessive skin absorption after fractional laser resurfacing.

  15. Absorption-desorption of drugs in porous polymers obtained by plasma; Absorcion-desorcion de farmacos en polimeros porosos obtenidos por plasma

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez T, M.

    2016-07-01

    A study about drug absorption and release in plasma polymers is presented in this work, these materials can be used as implants in the human body. In these applications the polymer should be biocompatible and/or biodegradable. Poly pyrroles and poly allylamine s synthesized by plasma have amine groups in their structure which makes them biocompatible with potential as drug carriers. In this function, the polymers were lyophilized to induce pores where the drug can be hosted. Drug-polymer mixtures with 1:10 ratio were prepared. The mixture morphology was studied by Scanning Electron Microscopy while their chemical structure was studied by Infrared Spectroscopy and X-ray Photoelectron Spectroscopy. Two models were studied to assess drug release, dynamic and static, in two solutions: water and Krebs Ringer (Kr) using the UV characteristic absorbance of each drug. In the static model release, 5 mg of the mixture were placed in 10 ml of solution. In the dynamic model, the release was performed with 5 mg of the mixture in 10 ml of solution, 1.5 ml of release medium was removed for UV analysis and replaced with an equal volume of fresh medium. The results indicate that the morphology of the polymers was modified with the lyophilization, in Poly pyrrole pores were induced with diameter in the range of 0.7 to 19 μm, while in Polyallyl amine the surface changed from smooth to rough. Drugs were absorbed in Poly pyrrole by filling the pores first and then coating the polymer with a drug layer. In Poly allylamine the drugs adhered to the polymer surface. Analyzing the atomic orbitals of the mixtures, it was found that the drugs interacted with the polymer. The most affected orbital was S2p, whose separation between 1/2 and 3/2 sub orbitals increased from 0.9 eV in Dapsone and Heparin to 4 eV in the mixtures, where the oxidation state changed from valence 6 to 6 and 2 in the mixtures. This suggests physicochemical interaction between drug and polymer. The drugs were released

  16. Studies on effective atomic numbers for photon energy absorption and electron density of some narcotic drugs in the energy range 1 keV-20 MeV

    Science.gov (United States)

    Gounhalli, Shivraj G.; Shantappa, Anil; Hanagodimath, S. M.

    2013-04-01

    Effective atomic numbers for photon energy absorption ZPEA,eff, photon interaction ZPI,eff and for electron density Nel, have been calculated by a direct method in the photon-energy region from 1 keV to 20 MeV for narcotic drugs, such as Heroin (H), Cocaine (CO), Caffeine (CA), Tetrahydrocannabinol (THC), Cannabinol (CBD), Tetrahydrocannabivarin (THCV). The ZPEA,eff, ZPI,eff and Nel values have been found to change with energy and composition of the narcotic drugs. The energy dependence ZPEA,eff, ZPI,eff and Nel is shown graphically. The maximum difference between the values of ZPEA,eff, and ZPI,eff occurs at 30 keV and the significant difference of 2 to 33% for the energy region 5-100 keV for all drugs. The reason for these differences is discussed.

  17. Competitive release and facilitation of drug-resistant parasites after therapeutic chemotherapy in a rodent malaria model

    Science.gov (United States)

    Wargo, A.R.; Huijben, S.; De Roode, J. C.; Shepherd, J.; Read, A.F.

    2007-01-01

    Malaria infections frequently consist of mixtures of drug-resistant and drug-sensitive parasites. If crowding occurs, where clonal population densities are suppressed by the presence of coinfecting clones, removal of susceptible clones by drug treatment could allow resistant clones to expand into the newly vacated niche space within a host. Theoretical models show that, if such competitive release occurs, it can be a potent contributor to the strength of selection, greatly accelerating the rate at which resistance spreads in a population. A variety of correlational field data suggest that competitive release could occur in human malaria populations, but direct evidence cannot be ethically obtained from human infections. Here we show competitive release after pyrimethamine curative chemotherapy of acute infections of the rodent malaria Plasmodium chabaudi in laboratory mice. The expansion of resistant parasite numbers after treatment resulted in enhanced transmission-stage densities. After the elimination or near-elimination of sensitive parasites, the number of resistant parasites increased beyond that achieved when a competitor had never been present. Thus, a substantial competitive release occurred, markedly elevating the fitness advantages of drug resistance above those arising from survival alone. This finding may explain the rapid spread of drug resistance and the subsequently brief useful lifespans of some antimalarial drugs. In a second experiment, where subcurative chemotherapy was administered, the resistant clone was only partly released from competitive suppression and experienced a restriction in the size of its expansion after treatment. This finding raises the prospect of harnessing in-host ecology to slow the spread of drug resistance. ?? 2007 by The National Academy of Sciences of the USA.

  18. Micro-segmental hair analysis for proving drug-facilitated crimes: Evidence that a victim ingested a sleeping aid, diphenhydramine, on a specific day.

    Science.gov (United States)

    Kuwayama, Kenji; Nariai, Maika; Miyaguchi, Hajime; Iwata, Yuko T; Kanamori, Tatsuyuki; Tsujikawa, Kenji; Yamamuro, Tadashi; Segawa, Hiroki; Abe, Hiroko; Iwase, Hirotaro; Inoue, Hiroyuki

    2018-07-01

    Sleeping aids are often abused in the commission of drug-facilitated crimes. Generally, there is little evidence that a victim ingested a spiked drink unknowingly because the unconscious victim cannot report the situation to the police immediately after the crime occurred. Although conventional segmental hair analysis can estimate the number of months since a targeted drug was ingested, this analysis cannot determine the specific day of ingestion. We recently developed a method of micro-segmental hair analysis using internal temporal markers (ITMs) to estimate the day of drug ingestion. This method was based on volunteer ingestion of ITMs to determine a timescale within individual hair strands, by segmenting a single hair strand at 0.4-mm intervals, corresponding to daily hair growth. This study assessed the ability of this method to estimate the day of ingestion of an over-the-counter sleeping aid, diphenhydramine, which can be easily abused. To model ingestion of a diphenhydramine-spiked drink unknowingly, each subject ingested a dose of diphenhydramine, followed by ingestion of two doses of the ITM, chlorpheniramine, 14days apart. Several hair strands were collected from each subject's scalp several weeks after the second ITM ingestion. Diphenhydramine and ITM were detected at specific regions within individual hair strands. The day of diphenhydramine ingestion was estimated from the distances between the regions and the days of ITM ingestion. The error between estimated and actual ingestion day ranged from -0.1 to 1.9days regardless of subjects and hair collection times. The total time required for micro-segmental analysis of 96 hair segments (hair length: 3.84cm) was approximately 2days and the cost was almost the same as in general drug analysis. This procedure may be applicable to the investigation of crimes facilitated by various drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Cytotoxicity Enhancement in Breast Cancer Cells with Carbonate Apatite-Facilitated Intracellular Delivery of Anti-Cancer Drugs

    Directory of Open Access Journals (Sweden)

    Tahereh Fatemian

    2018-02-01

    Full Text Available Pharmacotherapy as the mainstay in the management of breast cancer has demonstrated various drawbacks, including non-targeted bio distribution and narrow therapeutic and safety windows. Thus, enhancements in pharmacodynamic and pharmacokinetic profiles of the classical anti-cancer drugs could lead to improved efficacy against cancer cells. Therefore, inorganic pH-dependent carbonate apatite (CA nanoparticles were utilized to efficiently deliver various drugs into cancer cells. Following characterization and various modifications in the structure of CA complexes with different drugs, lifted outcomes were achieved. Markedly, complexing paclitaxel with CA resulted in 20.71 ± 4.34% loading efficiency together with 24.14 ± 2.21% enhancement in cytotoxicity on MCF-7 cells plus superior in vivo anti-tumour efficacy compared to free paclitaxel.

  20. Cytotoxicity Enhancement in Breast Cancer Cells with Carbonate Apatite-Facilitated Intracellular Delivery of Anti-Cancer Drugs

    Science.gov (United States)

    Fatemian, Tahereh; Chowdhury, Ezharul Hoque

    2018-01-01

    Pharmacotherapy as the mainstay in the management of breast cancer has demonstrated various drawbacks, including non-targeted bio distribution and narrow therapeutic and safety windows. Thus, enhancements in pharmacodynamic and pharmacokinetic profiles of the classical anti-cancer drugs could lead to improved efficacy against cancer cells. Therefore, inorganic pH-dependent carbonate apatite (CA) nanoparticles were utilized to efficiently deliver various drugs into cancer cells. Following characterization and various modifications in the structure of CA complexes with different drugs, lifted outcomes were achieved. Markedly, complexing paclitaxel with CA resulted in 20.71 ± 4.34% loading efficiency together with 24.14 ± 2.21% enhancement in cytotoxicity on MCF-7 cells plus superior in vivo anti-tumour efficacy compared to free paclitaxel. PMID:29401738

  1. Drug quantification in turbid media by fluorescence imaging combined with light-absorption correction using white Monte Carlo simulations

    DEFF Research Database (Denmark)

    Xie, Haiyan; Liu, Haichun; Svenmarker, Pontus

    2011-01-01

    Accurate quantification of photosensitizers is in many cases a critical issue in photodynamic therapy. As a noninvasive and sensitive tool, fluorescence imaging has attracted particular interest for quantification in pre-clinical research. However, due to the absorption of excitation and emission...... in vivo by the fluorescence imaging technique. In this paper we present a novel approach to compensate for the light absorption in homogeneous turbid media both for the excitation and emission light, utilizing time-resolved fluorescence white Monte Carlo simulations combined with the Beer-Lambert law......-absorption correction and absolute fluorophore concentrations. These results suggest that the technique potentially provides the means to quantify the fluorophore concentration from fluorescence images. © 2011 Society of Photo-Optical Instrumentation Engineers (SPIE)....

  2. Rapid freeze-drying cycle optimization using computer programs developed based on heat and mass transfer models and facilitated by tunable diode laser absorption spectroscopy (TDLAS).

    Science.gov (United States)

    Kuu, Wei Y; Nail, Steven L

    2009-09-01

    Computer programs in FORTRAN were developed to rapidly determine the optimal shelf temperature, T(f), and chamber pressure, P(c), to achieve the shortest primary drying time. The constraint for the optimization is to ensure that the product temperature profile, T(b), is below the target temperature, T(target). Five percent mannitol was chosen as the model formulation. After obtaining the optimal sets of T(f) and P(c), each cycle was assigned with a cycle rank number in terms of the length of drying time. Further optimization was achieved by dividing the drying time into a series of ramping steps for T(f), in a cascading manner (termed the cascading T(f) cycle), to further shorten the cycle time. For the purpose of demonstrating the validity of the optimized T(f) and P(c), four cycles with different predicted lengths of drying time, along with the cascading T(f) cycle, were chosen for experimental cycle runs. Tunable diode laser absorption spectroscopy (TDLAS) was used to continuously measure the sublimation rate. As predicted, maximum product temperatures were controlled slightly below the target temperature of -25 degrees C, and the cascading T(f)-ramping cycle is the most efficient cycle design. In addition, the experimental cycle rank order closely matches with that determined by modeling.

  3. Drug- or Alcohol-Facilitated, Incapacitated, and Forcible Rape in Relationship to Mental Health among a National Sample of Women

    Science.gov (United States)

    Zinzow, Heidi M.; Resnick, Heidi S.; Amstadter, Ananda B.; McCauley, Jenna L.; Ruggiero, Kenneth J.; Kilpatrick, Dean G.

    2010-01-01

    Rape is a well-established risk factor for mental health disorders such as posttraumatic stress disorder (PTSD) and depression. However, most studies have focused on forcible rape tactics and have not distinguished these from tactics that involve drug or alcohol intoxication. The authors' aim was to examine correlates of PTSD and depression in a…

  4. Assessment of veterinary drugs in plants using pharmacokinetic approaches: The absorption, distribution and elimination of tetracycline and sulfamethoxazole in ephemeral vegetables

    Science.gov (United States)

    Chen, Hui-Ru; Rairat, Tirawat; Loh, Shih-Hurng; Wu, Yu-Chieh; Vickroy, Thomas W.

    2017-01-01

    The present study was carried out to demonstrate novel use of pharmacokinetic approaches to characterize drug behaviors/movements in the vegetables with implications to food safety. The absorption, distribution, metabolism and most importantly, the elimination of tetracycline (TC) and sulfamethoxazole (SMX) in edible plants Brassica rapa chinensis and Ipomoea aquatica grown hydroponically were demonstrated and studied using non-compartmental pharmacokinetic analysis. The results revealed drug-dependent and vegetable-dependent pharmacokinetic differences and indicated that ephemeral vegetables could have high capacity accumulating antibiotics (up to 160 μg g-1 for TC and 38 μg g-1 for SMX) within hours. TC concentration in the root (Cmax) could reach 11 times higher than that in the cultivation fluid and 3–28 times higher than the petioles/stems. Based on the volume of distribution (Vss), SMX was 3–6 times more extensively distributed than TC. Both antibiotics showed evident, albeit slow elimination phase with elimination half-lives ranging from 22 to 88 hours. For the first time drug elimination through the roots of a plant was demonstrated, and by viewing the root as a central compartment and continuous infusion without a loading dose as drug administration mode, it is possible to pharmacokinetically monitor the movement of antibiotics and their fate in the vegetables with more detailed information not previously available. Phyto-pharmacokinetic could be a new area worth developing new models for the assessment of veterinary drugs in edible plants. PMID:28797073

  5. Secreted phospholipase A(2) as a new enzymatic trigger mechanism for localised liposomal drug release and absorption in diseased tissue

    DEFF Research Database (Denmark)

    Davidsen, Jesper; Jørgensen, K.; Andresen, Thomas Lars

    2003-01-01

    Polymer-coated liposomes can act as versatile drug-delivery systems due to long vascular circulation time and passive targeting by leaky blood vessels in diseased tissue. We present an experimental model system illustrating a new principle for improved and programmable drug-delivery, which takes ...

  6. Alleged drug facilitated sexual assault (DFSA) in Northern Ireland from 1999 to 2005. A study of blood alcohol levels.

    Science.gov (United States)

    Hall, Janet; Goodall, Edward A; Moore, Tara

    2008-11-01

    Alleged sexual assault cases, identified from the forensic science Northern Ireland (FSNI) database, which had toxicology assays carried out on either blood or urine samples, were examined for the years 1999 up to and including 2005. In 1999 there were 30 toxicology requests while in 2005 there were 51, representing a 70% increase. The percentage of cases containing alcohol, drugs or both increased from 66% in 1999 to 78% in 2005. The estimated average blood alcohol concentration remained broadly similar throughout the spread of years. It was found to be 218mg% (milligrams per 100 millilitres) in 1999 and 217mg% in 2005. The actual number of cases studied within the 12h cut-off time rose from 9 in 1999 to 22 in 2005. The relationship between negative toxicology results and time delay between the alleged assault and forensic sampling was examined. This showed that between 44% and 74% of cases were found to have a time delay of >12h. Some of these cases may therefore represent false negative results. The presence of drugs, either alone or in combination with other drugs, doubled between 1999 and 2005. Increased identification was found with antidepressants, recreational drugs, benzodiazepines and analgesics, some of which were also associated with alcohol consumption. The findings are sufficient to cause alarm for the health and safety of certain individuals and their increased vulnerability to sexual assault in some social settings. Additionally, the legal implications of what constitutes valid consent needs to be considered further in the light of these findings, if attrition rates are to improve.

  7. Combining in vitro and in silico methods for better prediction of surfactant effects on the absorption of poorly water soluble drugs-a fenofibrate case example.

    Science.gov (United States)

    Berthelsen, Ragna; Sjögren, Erik; Jacobsen, Jette; Kristensen, Jakob; Holm, René; Abrahamsson, Bertil; Müllertz, Anette

    2014-10-01

    The aim of this study was to develop a sensitive and discriminative in vitro-in silico model able to simulate the in vivo performance of three fenofibrate immediate release formulations containing different surfactants. In addition, the study was designed to investigate the effect of dissolution volume when predicting the oral bioavailability of the formulations. In vitro dissolution studies were carried out using the USP apparatus 2 or a mini paddle assembly, containing 1000 mL or 100mL fasted state biorelevant medium, respectively. In silico simulations of small intestinal absorption were performed using the GI-Sim absorption model. All simulation runs were performed twice adopting either a total small intestinal volume of 533 mL or 105 mL, in order to examine the implication of free luminal water volumes for the in silico predictions. For the tested formulations, the use of a small biorelevant dissolution volume was critical for in vitro-in silico prediction of drug absorption. Good predictions, demonstrating rank order in vivo-in vitro-in silico correlations for Cmax, were obtained with in silico predictions utilizing a 105 mL estimate for the human intestinal water content combined with solubility and dissolution data performed in a mini paddle apparatus with 100mL fasted state simulated media. Copyright © 2014. Published by Elsevier B.V.

  8. A heuristic model to quantify the impact of excess cyclodextrin on oral drug absorption from aqueous solution

    DEFF Research Database (Denmark)

    Olesen, Niels Erik; Westh, Peter; Holm, René

    2016-01-01

    , the cyclodextrin concentration in the drug product must be higher than the amount needed to solubilise the compound, due to the displacement of the drug from the cyclodextrin cavity by bile salts in the intestinal lumen. On the other hand, dosing cyclodextrin at View the MathML source>DtotSC is expected to result...... the implication of having excess cyclodextrin in an oral solution....

  9. A tale of two citizens: a State Attorney General and a hematologist facilitate translation of research into US Food and Drug Administration actions--a SONAR report.

    Science.gov (United States)

    Chen, Brian; Restaino, John; Norris, LeAnn; Xirasagar, Sudha; Qureshi, Zaina P; McKoy, June M; Lopez, Isaac S; Trenery, Alyssa; Murday, Alanna; Kahn, Adam; Mattison, Donald R; Ray, Paul; Sartor, Oliver; Bennett, Charles L

    2012-11-01

    Pharmaceutical safety is a public health issue. In 2005, the Connecticut Attorney General (AG) raised concerns over adverse drug reactions in off-label settings, noting that thalidomide was approved to treat a rare illness, but more than 90% of its use was off label. A hematologist had reported thalidomide with doxorubicin or dexamethasone was associated with venous thromboembolism (VTE) rates of 25%. We review US Food and Drug Administration (FDA) and manufacturer responses to a citizen petition filed to address these thalidomide safety issues. Case study. The AG petitioned the FDA requesting thalidomide-related safety actions. Coincidentally, the manufacturer submitted a supplemental New Drug Approval (sNDA), requesting approval to treat multiple myeloma with thalidomide-dexamethasone. FDA safety officers reviewed the petition and the literature and noted that VTE risks with thalidomide were not appropriately addressed in the existing package insert. In the sNDA application, the manufacturer reported thalidomide-associated toxicities for multiple myeloma were primarily somnolence and neurotoxicity, and a proposed package insert did not focus on VTE risks. In October, the FDA informed the Oncology Drug Division that VTE risks with thalidomide were poorly addressed in the existing label. After reviewing this memorandum, an Oncology Drug Division reviewer informed the manufacturer that approval of the sNDA would be delayed until several thalidomide-associated VTE safety actions, including revisions of the package insert, were implemented. The manufacturer and FDA agreed on these actions, and the sNDA was approved. New approaches addressing off-label safety are needed. The conditions that facilitated the successful response to this citizen petition are uncommon.

  10. A Tale of Two Citizens: A State Attorney General and a Hematologist Facilitate Translation of Research Into US Food and Drug Administration Actions—A SONAR Report

    Science.gov (United States)

    Chen, Brian; Restaino, John; Norris, LeAnn; Xirasagar, Sudha; Qureshi, Zaina P.; McKoy, June M.; Lopez, Isaac S.; Trenery, Alyssa; Murday, Alanna; Kahn, Adam; Mattison, Donald R.; Ray, Paul; Sartor, Oliver; Bennett, Charles L.

    2012-01-01

    Purpose: Pharmaceutical safety is a public health issue. In 2005, the Connecticut Attorney General (AG) raised concerns over adverse drug reactions in off-label settings, noting that thalidomide was approved to treat a rare illness, but more than 90% of its use was off label. A hematologist had reported thalidomide with doxorubicin or dexamethasone was associated with venous thromboembolism (VTE) rates of 25%. We review US Food and Drug Administration (FDA) and manufacturer responses to a citizen petition filed to address these thalidomide safety issues. Methods: Case study. Results: The AG petitioned the FDA requesting thalidomide-related safety actions. Coincidentally, the manufacturer submitted a supplemental New Drug Approval (sNDA), requesting approval to treat multiple myeloma with thalidomide-dexamethasone. FDA safety officers reviewed the petition and the literature and noted that VTE risks with thalidomide were not appropriately addressed in the existing package insert. In the sNDA application, the manufacturer reported thalidomide-associated toxicities for multiple myeloma were primarily somnolence and neurotoxicity, and a proposed package insert did not focus on VTE risks. In October, the FDA informed the Oncology Drug Division that VTE risks with thalidomide were poorly addressed in the existing label. After reviewing this memorandum, an Oncology Drug Division reviewer informed the manufacturer that approval of the sNDA would be delayed until several thalidomide-associated VTE safety actions, including revisions of the package insert, were implemented. The manufacturer and FDA agreed on these actions, and the sNDA was approved. Conclusion: New approaches addressing off-label safety are needed. The conditions that facilitated the successful response to this citizen petition are uncommon. PMID:23598851

  11. Exploring the Barriers to and Facilitators of Using Evidence-Based Drugs in the Secondary Prevention of Cardiovascular Diseases: Findings From a Multistakeholder, Qualitative Analysis.

    Science.gov (United States)

    Miller, Victoria; Nambiar, Lavanya; Saxena, Malvika; Leong, Darryl; Banerjee, Amitava; Werba, José Pablo; Faria Neto, Jose Rocha; Quinto, Katherine Curi; Moniruzzaman, Mohammed; Khandelwal, Shweta

    2018-03-01

    Health-system barriers and facilitators associated with cardiovascular medication adherence have seldom been studied, particularly in low- and middle-income countries where uptake rates are poorest. This study sought to explore the major obstacles and facilitators to the use of evidence-supported medications for secondary prevention of cardiovascular disease using qualitative analysis in 2 diverse countries across multiple levels of their health care systems. A qualitative descriptive study approach was implemented in Hamilton, Ontario, Canada, and Delhi, India. A purposeful sample (n = 69) of 23 patients, 10 physicians, 2 nurse practitioners, 5 Department of Ayurveda, Yoga and Naturopathy, Unani, Siddha, and Homoeopathy physicians, 11 pharmacists, 3 nurses, 4 hospital administrators, 1 social worker, 3 nongovernmental organization workers, 2 pharmaceutical company representatives, and 5 policy makers participated in interviews in Hamilton, Ontario, Canada (n = 21), and Delhi, India (n = 48). All interviews were digitally recorded and transcribed followed by directed content analysis to summarize and categorize the interviews. Themes that emerged across the stakeholder groups included: medication counseling; monitoring adherence; medication availability; medication affordability and drug coverage; time restrictions; and task shifting. The depth of verbal medication counseling provided varied substantially between countries, with prescribers in India unable to convey relevant information about drug treatments due to time constraint and high patient load. Canadian patients reported drug affordability as a common issue and very few patients were familiar with government subsidized drug programs. In India, patients purchased medications out-of-pocket from private, community pharmacies to avoid long commutes, lost wages, and unavailability of medications from hospitals formularies. Task shifting medication-refilling and titration to nonphysician health workers was

  12. Effect of pH and comedication on gastrointestinal absorption of posaconazole: monitoring of intraluminal and plasma drug concentrations.

    Science.gov (United States)

    Walravens, Jeroen; Brouwers, Joachim; Spriet, Isabel; Tack, Jan; Annaert, Pieter; Augustijns, Patrick

    2011-11-01

    Posaconazole (Noxafil®) is an extended-spectrum triazole antifungal agent for prevention and treatment of invasive fungal infections. An inadequate dietary intake and abnormal gastric pH levels are common in critically ill patients receiving antifungal treatment with posaconazole, resulting in unpredictable bioavailability and sub-therapeutic plasma concentrations. This study was carried out to elucidate the impact of pH on posaconazole absorption and to explore the underlying mechanisms of enhanced intestinal absorption when coadministering an acidic carbonated beverage. In contrast to previously published studies, in which only plasma concentrations were determined, we also explored the gastric and intestinal behaviour of posaconazole after a single oral dose. A crossover study was performed in five healthy subjects. A single dose (10 mL) of posaconazole suspension (40 mg/mL) was administered orally in four different conditions: with 330 mL of water (condition 1); with 330 mL of a cola beverage [Coca-Cola®] (condition 2); with 330 mL of water following intake of the proton pump inhibitor esomeprazole 40 mg once daily for 3 days (condition 3); or with 330 mL of Coca-Cola® following intake of esomeprazole 40 mg once daily for 3 days (condition 4). After administration, gastrointestinal fluid and plasma samples were collected at regular time points, and posaconazole concentrations were determined. Compared with administration with water, coadministration of Coca-Cola® did not alter the pH of the intraluminal environment but did significantly increase posaconazole gastric concentrations (+102%; p Coca-Cola® and prolonged gastric residence. Coadministration of esomeprazole led to an increased gastric pH, which was accompanied by decreased posaconazole absorption; the mean plasma and gastric area under the concentration-time curve (AUC) values decreased by 37% and 84%, respectively. Simultaneous intake of Coca-Cola® could not completely compensate for the

  13. Information sought, information shared: exploring performance and image enhancing drug user-facilitated harm reduction information in online forums.

    Science.gov (United States)

    Tighe, Boden; Dunn, Matthew; McKay, Fiona H; Piatkowski, Timothy

    2017-07-21

    There is good evidence to suggest that performance and image enhancing drug (PIED) use is increasing in Australia and that there is an increase in those using PIEDs who have never used another illicit substance. Peers have always been an important source of information in this group, though the rise of the Internet, and the increased use of Internet forums amongst substance consumers to share harm reduction information, means that PIED users may have access to a large array of views and opinions. The aim of this study was to explore the type of information that PIED users seek and share on these forums. An online search was conducted to identify online forums that discussed PIED use. Three discussion forums were included in this study: aussiegymjunkies.com, bodybuildingforums.com.au, and brotherhoodofpain.com. The primary source of data for this study was the 'threads' from the online forums. Threads were thematically analysed for overall content, leading to the identification of themes. One hundred thirty-four threads and 1716 individual posts from 450 unique avatars were included in this analysis. Two themes were identified: (1) personal experiences and advice and (2) referral to services and referral to the scientific literature. Internet forums are an accessible way for members of the PIED community to seek and share information to reduce the harms associated with PIED use. Forum members show concern for both their own and others' use and, where they lack information, will recommend seeking information from medical professionals. Anecdotal evidence is given high credence though the findings from the scientific literature are used to support opinions. The engagement of health professionals within forums could prove a useful strategy for engaging with this population to provide harm reduction interventions, particularly as forum members are clearly seeking further reliable information, and peers may act as a conduit between users and the health and medical

  14. Rapid molecular detection of rifampicin resistance facilitates early diagnosis and treatment of multi-drug resistant tuberculosis: case control study.

    Directory of Open Access Journals (Sweden)

    Philly O'Riordan

    2008-09-01

    Full Text Available Multi-drug resistant tuberculosis (MDR-TB is a major public health concern since diagnosis is often delayed, increasing the risk of spread to the community and health care workers. Treatment is prolonged, and the total cost of treating a single case is high. Diagnosis has traditionally relied upon clinical suspicion, based on risk factors and culture with sensitivity testing, a process that can take weeks or months. Rapid diagnostic molecular techniques have the potential to shorten the time to commencing appropriate therapy, but have not been put to the test under field conditions.This retrospective case-control study aimed to identify risk factors for MDR-TB, and analyse the impact of testing for rifampicin resistance using RNA polymerase B (rpoB mutations as a surrogate for MDR-TB. Forty two MDR-TB cases and 84 fully sensitive TB controls were matched by date of diagnosis; and factors including demographics, clinical presentation, microbiology findings, management and outcome were analysed using their medical records. Conventionally recognised risk factors for MDR-TB were absent in almost half (43% of the cases, and 15% of cases were asymptomatic. A significant number of MDR-TB cases were identified in new entrants to the country. Using rpoB mutation testing, the time to diagnosis of MDR-TB was dramatically shortened by a median of 6 weeks, allowing patients to be commenced on appropriate therapy a median of 51days earlier than those diagnosed by conventional culture and sensitivity testing.MDR-TB is frequently an unexpected finding, may be asymptomatic, and is particularly prevalent among TB infected new entrants to the country. Molecular resistance testing of all acid fast bacilli positive specimens has the potential to rapidly identify MDR-TB patients and commence them on appropriate therapy significantly earlier than by conventional methods.

  15. Prenatal exposure to ethanol during late gestation facilitates operant self-administration of the drug in 5-day-old rats.

    Science.gov (United States)

    Miranda-Morales, Roberto Sebastián; Nizhnikov, Michael E; Spear, Norman E

    2014-02-01

    Prenatal ethanol exposure modifies postnatal affinity to the drug, increasing the probability of ethanol use and abuse. The present study tested developing rats (5-day-old) in a novel operant technique to assess the degree of ethanol self-administration as a result of prenatal exposure to low ethanol doses during late gestation. On a single occasion during each of gestational days 17-20, pregnant rats were intragastrically administered ethanol 1 g/kg, or water (vehicle). On postnatal day 5, pups were tested on a novel operant conditioning procedure in which they learned to touch a sensor to obtain 0.1% saccharin, 3% ethanol, or 5% ethanol. Immediately after a 15-min training session, a 6-min extinction session was given in which operant behavior had no consequence. Pups were positioned on a smooth surface and had access to a touch-sensitive sensor. Physical contact with the sensor activated an infusion pump, which served to deliver an intraoral solution as reinforcement (Paired group). A Yoked control animal evaluated at the same time received the reinforcer when its corresponding Paired pup touched the sensor. Operant behavior to gain access to 3% ethanol was facilitated by prenatal exposure to ethanol during late gestation. In contrast, operant learning reflecting ethanol reinforcement did not occur in control animals prenatally exposed to water only. Similarly, saccharin reinforcement was not affected by prenatal ethanol exposure. These results suggest that in 5-day-old rats, prenatal exposure to a low ethanol dose facilitates operant learning reinforced by intraoral administration of a low-concentration ethanol solution. This emphasizes the importance of intrauterine experiences with ethanol in later susceptibility to drug reinforcement. The present operant conditioning technique represents an alternative tool to assess self-administration and seeking behavior during early stages of development. Published by Elsevier Inc.

  16. Statins, fibrates, nicotinic acid, cholesterol absorption inhibitors, anion-exchange resins, omega-3 fatty acids: which drugs for which patients?

    Science.gov (United States)

    Drexel, Heinz

    2009-12-01

    Classes of lipid lowering drugs differ strongly with respect to the types of lipids or lipoproteins they predominantly affect. Statins inhibit the de-novo synthesis of cholesterol. Consequently, the liver produces less VLDL, and the serum concentration primarily of LDL cholesterol (but, to a lesser extent, also of triglycerides) is lowered. Further, statins somewhat increase HDL cholesterol. There is abundant evidence that statins lower the rate of cardiovascular events. Cardiovascular risk reduction is the better, the lower the LDL cholesterol values achieved with statin therapy are. Some evidence is available that anion exchange resins which also decrease LDL cholesterol decrease vascular risk, too. This is not the case for the ezetimibe, which strongly lowers LDL cholesterol: its potential to decrease vascular risk remains to be proven. In contrast evidence for cardiovascular risk reduction through the mainly triglyceride lowering fibrates as well as for niacin is available. Niacin is the most potent HDL increasing drug currently available and besides increasing HDL cholesterol efficaciously lowers triglycerides and LDL cholesterol. Large ongoing trials address the decisive question whether treatment with fibrates and niacin provides additional cardiovascular risk reduction when given in addition to statin treatment.

  17. “We fear the police, and the police fear us”: Structural and individual barriers and facilitators to HIV medication adherence among injection drug users in Kiev, Ukraine

    Science.gov (United States)

    Mimiaga, Matthew J.; Safren, Steven A.; Dvoryak, Sergiy; Reisner, Sari L.; Needle, Richard; Woody, George

    2010-01-01

    Ukraine has one of the most severe HIV/AIDS epidemics in Europe, with an estimated 1.63% of the population living with HIV/AIDS in 2007. Injection drug use (IDU) remains the predominant mode of transmission in Kiev—the capital and largest city. Prior reports suggest that the HIV infection rate among IDUs in Kiev reaches 33%, and many have poor and inequitable access to highly active antiretroviral therapy (HAART). Among those with access to HAART, little is understood about barriers and facilitators to HAART medication adherence. In 5/2009, two semi-structured focus groups were conducted with HIV-infected IDUs seeking treatment at the City AIDS Center, Kiev. The goal was to use this information to adapt and tailor, to Ukrainian culture, an evidence-based intervention for improving adherence to HAART. All 16 participants attributed HIV infection to IDU. Their average age was 31.6 (SD=7.0), average time with HIV 5.7 years (SD=4.0), average time on HAART 2.5 years (SD=1.7), average time as IDU 14.6 years (SD=6.8), and 88% were on opioid substitution therapy. The most salient themes related to adherence barriers included: (1) harassment and discrimination by police; (2) opioid dependence; (3) complexity of drug regimen; (4) side effects; (5) forgetting; (6) co-occurring mental health problems; and (7) HIV stigma. Facilitators of adherence included: (1) cues for pill taking; (2) support and reminders from family, significant other, and friends; (3) opioid substitution therapy; and (4) wanting improved health. Additional factors explored included: 1) knowledge about HAART; (2) storage of medications; and (3) IDU and sexual risk behaviors. Findings highlighted structural and individual barriers to adherence. At the structural level, police discrimination and harassment was reported to be a major barrier to adherence to opioid substitution therapy and HAART. Privacy and stigma were barriers at the individual level. Recommendations for adherence interventions included

  18. The Small GTPase Rac1 Contributes to Extinction of Aversive Memories of Drug Withdrawal by Facilitating GABAA Receptor Endocytosis in the vmPFC.

    Science.gov (United States)

    Wang, Weisheng; Ju, Yun-Yue; Zhou, Qi-Xin; Tang, Jian-Xin; Li, Meng; Zhang, Lei; Kang, Shuo; Chen, Zhong-Guo; Wang, Yu-Jun; Ji, Hui; Ding, Yu-Qiang; Xu, Lin; Liu, Jing-Gen

    2017-07-26

    Extinction of aversive memories has been a major concern in neuropsychiatric disorders, such as anxiety disorders and drug addiction. However, the mechanisms underlying extinction of aversive memories are not fully understood. Here, we report that extinction of conditioned place aversion (CPA) to naloxone-precipitated opiate withdrawal in male rats activates Rho GTPase Rac1 in the ventromedial prefrontal cortex (vmPFC) in a BDNF-dependent manner, which determines GABA A receptor (GABA A R) endocytosis via triggering synaptic translocation of activity-regulated cytoskeleton-associated protein (Arc) through facilitating actin polymerization. Active Rac1 is essential and sufficient for GABA A R endocytosis and CPA extinction. Knockdown of Rac1 expression within the vmPFC of rats using Rac1-shRNA suppressed GABA A R endocytosis and CPA extinction, whereas expression of a constitutively active form of Rac1 accelerated GABA A R endocytosis and CPA extinction. The crucial role of GABA A R endocytosis in the LTP induction and CPA extinction is evinced by the findings that blockade of GABA A R endocytosis by a dynamin function-blocking peptide (Myr-P4) abolishes LTP induction and CPA extinction. Thus, the present study provides first evidence that Rac1-dependent GABA A R endocytosis plays a crucial role in extinction of aversive memories and reveals the sequence of molecular events that contribute to learning experience modulation of synaptic GABA A R endocytosis. SIGNIFICANCE STATEMENT This study reveals that Rac1-dependent GABA A R endocytosis plays a crucial role in extinction of aversive memories associated with drug withdrawal and identifies Arc as a downstream effector of Rac1 regulations of synaptic plasticity as well as learning and memory, thereby suggesting therapeutic targets to promote extinction of the unwanted memories. Copyright © 2017 the authors 0270-6474/17/377096-15$15.00/0.

  19. Delayed absorption of many (paracetamol, aspirin, other NSAIDs and zolmitriptan) but not all (sumatriptan, rizatriptan) drugs during migraine attacks and most likely normal gastric emptying outside attacks. A review

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer Carsten

    2017-01-01

    Background In most pharmacokinetic studies, the oral absorption of drugs is impaired during migraine attacks but exceptions occur. A study on gastric emptying using gastric scintigraphy indicated that gastric stasis also occurs interictally in migraine. These studies were reviewed critically. Res...

  20. Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin: Fragment-Based Drug Design Facilitated by Dynamic Combinatorial Chemistry.

    Science.gov (United States)

    Mondal, Milon; Radeva, Nedyalka; Fanlo-Virgós, Hugo; Otto, Sijbren; Klebe, Gerhard; Hirsch, Anna K H

    2016-08-01

    Fragment-based drug design (FBDD) affords active compounds for biological targets. While there are numerous reports on FBDD by fragment growing/optimization, fragment linking has rarely been reported. Dynamic combinatorial chemistry (DCC) has become a powerful hit-identification strategy for biological targets. We report the synergistic combination of fragment linking and DCC to identify inhibitors of the aspartic protease endothiapepsin. Based on X-ray crystal structures of endothiapepsin in complex with fragments, we designed a library of bis-acylhydrazones and used DCC to identify potent inhibitors. The most potent inhibitor exhibits an IC50 value of 54 nm, which represents a 240-fold improvement in potency compared to the parent hits. Subsequent X-ray crystallography validated the predicted binding mode, thus demonstrating the efficiency of the combination of fragment linking and DCC as a hit-identification strategy. This approach could be applied to a range of biological targets, and holds the potential to facilitate hit-to-lead optimization. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  1. Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin: Fragment‐Based Drug Design Facilitated by Dynamic Combinatorial Chemistry

    Science.gov (United States)

    Mondal, Milon; Radeva, Nedyalka; Fanlo‐Virgós, Hugo; Otto, Sijbren; Klebe, Gerhard

    2016-01-01

    Abstract Fragment‐based drug design (FBDD) affords active compounds for biological targets. While there are numerous reports on FBDD by fragment growing/optimization, fragment linking has rarely been reported. Dynamic combinatorial chemistry (DCC) has become a powerful hit‐identification strategy for biological targets. We report the synergistic combination of fragment linking and DCC to identify inhibitors of the aspartic protease endothiapepsin. Based on X‐ray crystal structures of endothiapepsin in complex with fragments, we designed a library of bis‐acylhydrazones and used DCC to identify potent inhibitors. The most potent inhibitor exhibits an IC50 value of 54 nm, which represents a 240‐fold improvement in potency compared to the parent hits. Subsequent X‐ray crystallography validated the predicted binding mode, thus demonstrating the efficiency of the combination of fragment linking and DCC as a hit‐identification strategy. This approach could be applied to a range of biological targets, and holds the potential to facilitate hit‐to‐lead optimization. PMID:27400756

  2. Isavuconazole absorption following oral administration in healthy subjects is comparable to intravenous dosing, and is not affected by food, or drugs that alter stomach pH.

    Science.gov (United States)

    Schmitt-Hoffmann, Anne; Desai, Amit; Kowalski, Donna; Pearlman, Helene; Yamazaki, Takao; Townsend, Robert

    2016-08-01

    Two openlabel, single-dose, randomized crossover studies and one open-label, multiple-dose, parallel group study in healthy volunteers were conducted with the prodrug, isavuconazonium sulfate, to determine absolute bioavailability of the active triazole, isavuconazole (EudraCT 2007-004949-15; n = 14), and the effect of food (EudraCT 2007- 004940-63; n = 26), and pH (NCT02128893; n = 24) on the absorption of isavuconazole. Isavuconazonium sulfate 744 mg designed to deliver 400 mg of the active triazole isavuconazole was administered in the absolute bioavailability (oral or intravenous (IV) (2-hour infusion)) and food-effect studies (oral). In the pH-effect study, isavuconazonium sulfate 372 mg designed to deliver 200 mg of isavuconazole was administered orally three times daily (t.i.d.) for 2 days, followed by a single daily oral dose for 3 days, in the presence of steady state esomeprazole dosed orally at 40 mg/day. Isavuconazole was well tolerated in each study. Bioavailability: Geometric least squares mean ratios (GLSMR; oral/IV) for isavuconazole AUC∞, and Cmax were 98% (90% confidence interval (CI): 94, 101) and 78% (90% CI: 72, 85), respectively. Food-effect: GLSMR (fed/fasted) for AUC∞ and Cmax of isavuconazole in plasma were 110% (90% CI: 102, 118) and 92% (90% CI: 86, 98), respectively. Median tmax was 5 hours with food and 3 hours under fasted conditions. pH-effect: GLSMR for isavuconazole AUCtau and Cmax were 108% (90% CI: 89, 130) and 105% (90% CI: 89, 124), respectively. Orally administered isavuconazonium sulfate effectively delivers isavuconazole, as evidenced by the fact that oral isavuconazole is bioequivalent to the IV formulation. Dose adjustments are not required when switching between oral and IV formulations, regardless of food or drugs that increase gastric pH.

  3. Effect of food intake and co-administration of placebo self-nanoemulsifying drug delivery systems on the absorption of cinnarizine in healthy human volunteers.

    Science.gov (United States)

    Christiansen, Martin Lau; Holm, Rene; Abrahamsson, Bertil; Jacobsen, Jette; Kristensen, Jakob; Andersen, Jens Rikardt; Müllertz, Anette

    2016-03-10

    Positive food effects may be observed for low aqueous soluble compounds, these effects could potentially be circumvented using lipid based formulations. However, as all compounds are not chemically stable in lipid based systems, alternative dosage regimes could be investigated to evade the stability issue. The two aims for this present study were therefore; i) to investigate if a nutritional drink, Fresubin Energy®, could induce food effect in humans for the poorly soluble compound cinnarizine; and ii) to investigate if co-administration of a self-nano-emulsifying drug delivery systems (SNEDDS) with a conventional cinnarizine tablet could reduce the observed food-effect. A commercial conventional cinnarizine tablet was dosed to 10 healthy volunteers in a cross-over design in both fasted and fed state, with and without co-administration of a SNEDDS, with a one week wash-out period between dosing. The fed state was induced using a nutritional drink (Fresubin Energy®) and gastric emptying was assessed by administration of paracetamol as a marker. The pharmacokinetic analysis showed that the nutritional drink delayed the uptake and increased the fraction of absorbed cinnarizine, indicative of a food effect on the compound. This was in agreement with a previous dog study and indicates that the nutritional drink can be used for inducing the same level of food effect in humans. Though not statistically significant, the co-administration of SNEDDS exhibited a tendency towards a reduction of the observed food effect and an increased absorption of cinnarizine in the fasted state; based upon the individual ratios, which was not reflected in the mean data. However, the co-administration of SNEEDS in the fasted state, also induce a slower gastric emptying rate, which was observed as a delayed tmax for both cinnarizine and paracetamol. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Study on the interactions of antiemetic drugs and 12-tungstophosphoric acid by absorption and resonance Rayleigh scattering spectra and their analytical applications

    Science.gov (United States)

    Wang, Yaqiong; Liu, Shaopu; Liu, Zhongfang; Yang, Jidong; Hu, Xiaoli

    2013-03-01

    In 0.1 mol L-1 HCl medium, antiemetic drugs (ATM), such as granisetron hydrochloride (GS) and tropisetron hydrochloride (TS), reacted with H3PW12O40·nH2O and formed 3:1 ion-association complex of [(ATM)3PW12O40], then self-aggregated into nanoparticles-[(ATM)3PW12O40]n with an average size of 100 nm. The reaction resulted in the enhancement of resonance Rayleigh scattering (RRS) and the absorption spectra. The increments of scattering intensity (ΔIRRS) and the change of absorbance (ΔA) were both directly proportional to the concentrations of ATM in certain ranges. Accordingly, two new RRS and spectrophotometric methods were proposed for ATM detection. The detection limits (3σ) of GS and TS were 3.2 ng mL-1 and 4.0 ng mL-1(RRS method), 112.5 ng mL-1 and 100.0 ng mL-1(spectrophotometric method). These two methods were applied to determine GS in orally disintegrating tablets and the results were in good agreement with the official method. The ground-state geometries and electronic structures of GS and TS were optimized by the hybrid density functional theory (DFT) method and the shape of [(ATM)3PW12O40]n was characterized by atomic force microscopy (AFM). Take the RRS method with higher sensitivity as an example, the reaction mechanism and the reasons for enhancement of scattering were discussed.

  5. Barriers and facilitating factors to the uptake of antiretroviral drugs for prevention of mother-to-child transmission of HIV in sub-Saharan Africa: a systematic review

    Science.gov (United States)

    Gourlay, Annabelle; Birdthistle, Isolde; Mburu, Gitau; Iorpenda, Kate; Wringe, Alison

    2013-01-01

    Objectives To investigate and synthesize reasons for low access, initiation and adherence to antiretroviral drugs by mothers and exposed babies for prevention of mother-to-child transmission (PMTCT) of HIV in sub-Saharan Africa. Methods A systematic literature review was conducted. Four databases were searched (Medline, Embase, Global Health and Web of Science) for studies conducted in sub-Saharan Africa from January 2000 to September 2012. Quantitative and qualitative studies were included that met pre-defined criteria. Antiretroviral (ARV) prophylaxis (maternal/infant) and combination antiretroviral therapy (ART) usage/registration at HIV care and treatment during pregnancy were included as outcomes. Results Of 574 references identified, 40 met the inclusion criteria. Four references were added after searching reference lists of included articles. Twenty studies were quantitative, 16 were qualitative and eight were mixed methods. Forty-one studies were conducted in Southern and East Africa, two in West Africa, none in Central Africa and one was multi-regional. The majority (n=25) were conducted before combination ART for PMTCT was emphasized in 2006. At the individual-level, poor knowledge of HIV/ART/vertical transmission, lower maternal educational level and psychological issues following HIV diagnosis were the key barriers identified. Stigma and fear of status disclosure to partners, family or community members (community-level factors) were the most frequently cited barriers overall and across time. The extent of partner/community support was another major factor impeding or facilitating the uptake of PMTCT ARVs, while cultural traditions including preferences for traditional healers and birth attendants were also common. Key health-systems issues included poor staff-client interactions, staff shortages, service accessibility and non-facility deliveries. Conclusions Long-standing health-systems issues (such as staffing and service accessibility) and community

  6. Examination of oral absorption and lymphatic transport of halofantrine in a triple-cannulated canine model after administration in self-microemulsifying drug delivery systems (SMEDDS) containing structured triglycerides

    DEFF Research Database (Denmark)

    Holm, René; Porter, Christopher J H; Edwards, Glenn A

    2003-01-01

    The potential for lipidic self-microemulsifying drug delivery systems (SMEDDS) containing triglycerides with a defined structure, where the different fatty acids on the glycerol backbone exhibit different metabolic fate, to improve the lymphatic transport and the portal absorption of a poorly water......-soluble drug, halofantrine, were investigated in fasted lymph cannulated canines. Two different structured triglycerides were incorporated into the SMEDDS; 1,3-dioctanoyl-2-linoleyl-sn-glycerol (C8:0-C18:2-C8:0) (MLM) and 1,3-dilinoyl-2-octanoyl-sn-glycerol (C18:2-C8:0-C18:2) (LML). A previously optimised...... availability was affected by the triglyceride incorporated into the multi-component delivery system and availabilities of 56.9% (MLM) and 37.2% (LML) were found. These data indicate that the pharmaceutical scientist can use the structure of the lipid to affect the relative contribution of the two absorption...

  7. Calcium absorption

    International Nuclear Information System (INIS)

    Carlmark, B.; Reizenstein, P.; Dudley, R.A.

    1976-01-01

    The methods most commonly used to measure the absorption and retention of orally administered calcium are reviewed. Nearly all make use of calcium radioisotopes. The magnitude of calcium absorption and retention depends upon the chemical form and amount of calcium administered, and the clinical and nutritional status of the subject; these influences are briefly surveyed. (author)

  8. Absorption studies

    International Nuclear Information System (INIS)

    Ganatra, R.D.

    1992-01-01

    Absorption studies were once quite popular but hardly anyone does them these days. It is easier to estimate the blood level of the nutrient directly by radioimmunoassay (RIA). However, the information obtained by estimating the blood levels of the nutrients is not the same that can be obtained from the absorption studies. Absorption studies are primarily done to find out whether some of the essential nutrients are absorbed from the gut or not and if they are absorbed, to determine how much is being absorbed. In the advanced countries, these tests were mostly done to detect pernicious anaemia where vitamin B 12 is not absorbed because of the lack of the intrinsic factor in the stomach. In the tropical countries, ''malabsorption syndrome'' is quire common. In this condition, several nutrients like fat, folic acid and vitamin B 12 are not absorbed. It is possible to study absorption of these nutrients by radioisotopic absorption studies

  9. Facilitating Transfers

    DEFF Research Database (Denmark)

    Kjær, Poul F.

    to specific logics of temporalisation and spatial expansion of a diverse set of social processes in relation to, for example, the economy, politics, science and the mass media. On this background, the paper will more concretely develop a conceptual framework for classifying different contextual orders...... that the essential functional and normative purpose of regulatory governance is to facilitate, stabilise and justify the transfer of condensed social components (such as economic capital and products, political decisions, legal judgements, religious beliefs and scientific knowledge) from one social contexts...

  10. Potentiation of intraocular absorption and drug metabolism of N-acetylcarnosine lubricant eye drops: drug interaction with sight threatening lipid peroxides in the treatment for age-related eye diseases.

    Science.gov (United States)

    Babizhayev, Mark A

    2009-01-01

    lenses obtained from patients with senile and complicated cataracts as compared to normal donors. Utilizing the pharmacokinetic studies and the specific purity N-acetylcarnosine (NAC) ingredient as a source of pharmacological principal L-carnosine, we have created an ophthalmic time-release prodrug form combined with a muco-adhesive lubricant compound carboxymethylcellulose and other essential corneal absorption promoter excipients tailoring the increased intraocular absorption of L-carnosine in the aqueous humor and optimizing its specific effect in producing the basic antioxidant activity in vivo and reducing toxic effects of lipid peroxides to the crystalline lens. L-Carnosine that finds its way into the aqueous humor can accumulate in the lens tissue for a reasonable period of time. However, administration of pure L-carnosine (1% solution) to the rabbit eye (instillation, subconjunctival injection) does not lead to accumulation of this natural compound in the aqueous humor over 30 min in concentration exceeding that in the placebo-treated matched eyes, and its effective concentration is exhausted more rapidly. The NAC prodrug eye drops optimize the clinical effects for the treatment of ophthalmic disorders (such as prevention and reversal of cataracts in human and animal [canine] eyes). The data provided predict a particular NAC ophthalmic prodrug's clinical effect; the suitable magnitude and duration of this effect suggest dose-related bioavailability of L-camosine released from NAC in the aqueous humor of the anterior eye segment. The ophthalmic NAC drug shows promise in the treatment of a range of ophthalmic disorders which have a component of oxidative stress in their genesis (including cataract and after-cataract, glaucoma, dry eye, vitreous floaters, inflammatory disorders, corneal, retinal and systemic diseases [such as diabetes mellitus and its ophthalmic complications]). The clinical efficacy of N-acetylcarnosine lubricant eye drops in ripe cataracts and

  11. Examination of oral absorption and lymphatic transport of halofantrine in a triple-cannulated canine model after administration in self-microemulsifying drug delivery systems (SMEDDS) containing structured triglycerides.

    Science.gov (United States)

    Holm, René; Porter, Christopher J H; Edwards, Glenn A; Müllertz, Anette; Kristensen, Henning G; Charman, William N

    2003-09-01

    The potential for lipidic self-microemulsifying drug delivery systems (SMEDDS) containing triglycerides with a defined structure, where the different fatty acids on the glycerol backbone exhibit different metabolic fate, to improve the lymphatic transport and the portal absorption of a poorly water-soluble drug, halofantrine, were investigated in fasted lymph cannulated canines. Two different structured triglycerides were incorporated into the SMEDDS; 1,3-dioctanoyl-2-linoleyl-sn-glycerol (C8:0-C18:2-C8:0) (MLM) and 1,3-dilinoyl-2-octanoyl-sn-glycerol (C18:2-C8:0-C18:2) (LML). A previously optimised SMEDDS formulation for halofantrine, comprising of triglyceride, Cremophor EL, Maisine 35-1 and ethanol was selected for bioavailability assessment. The extent of lymphatic transport via the thoracic duct was 17.9% of the dose for the animals dosed with the MLM SMEDDS and 27.4% for LML. Also the plasma availability was affected by the triglyceride incorporated into the multi-component delivery system and availabilities of 56.9% (MLM) and 37.2% (LML) were found. These data indicate that the pharmaceutical scientist can use the structure of the lipid to affect the relative contribution of the two absorption pathways. The MLM formulation produced a total bioavailability of 74.9%, which is higher than the total absorption previously observed after post-prandial administration. This could indicate the utility of disperse lipid-base formulations based on structured triglycerides for the oral delivery of halofantrine, and potentially other lipophilic drugs.

  12. Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin : Fragment-Based Drug Design Facilitated by Dynamic Combinatorial Chemistry

    NARCIS (Netherlands)

    Mondal, Milon; Radeva, Nedyalka; Fanlo-Virgos, Hugo; Otto, Sijbren; Klebe, Gerhard; Hirsch, Anna K. H.

    2016-01-01

    Fragment-based drug design (FBDD) affords active compounds for biological targets. While there are numerous reports on FBDD by fragment growing/optimization, fragment linking has rarely been reported. Dynamic combinatorial chemistry (DCC) has become a powerful hit-identification strategy for

  13. Facilitating participation

    DEFF Research Database (Denmark)

    Skøtt, Bo

    2018-01-01

    the resulting need for a redefinition of library competence. In doing this, I primarily address the first two questions from Chapter 1 and how they relate to the public’s informal, leisure-time activities in a networked society. In particular, I focus on the skills of reflexive self-perception and informed...... opinion formation. Further, I point out the significance which these informal leisure-time activities have for public library staff’s cultural dissemination skills. In this way, I take on the question of the skills required for facilitating the learning of a participatory public (cf. Chapter 1......), exemplifying with the competence required of library staff. My discussion will proceed by way of a literature review. In the next section, I shall explain how and what sources were chosen and section three and four present the theoretical framework and how the applied theories are related. In the fifth section...

  14. Facilitating Transfers

    DEFF Research Database (Denmark)

    Kjær, Poul F.

    2018-01-01

    Departing from the paradox that globalisation has implied an increase, rather than a decrease, in contextual diversity, this paper re-assesses the function, normative purpose and location of Regulatory Governance Frameworks in world society. Drawing on insights from sociology of law and world...... society studies, the argument advanced is that Regulatory Governance Frameworks are oriented towards facilitating transfers of condensed social components, such as economic capital and products, legal acts, political decisions and scientific knowledge, from one legally-constituted normative order, i.......e. contextual setting, to another. Against this background, it is suggested that Regulatory Governance Frameworks can be understood as schemes which act as ‘rites of passage’ aimed at providing legal stabilisation to social processes characterised by liminality, i.e ambiguity, hybridity and in-betweenness....

  15. Narrative absorption

    DEFF Research Database (Denmark)

    Narrative Absorption brings together research from the social sciences and Humanities to solve a number of mysteries: Most of us will have had those moments, of being totally absorbed in a book, a movie, or computer game. Typically we do not have any idea about how we ended up in such a state. No...

  16. An analysis of the hypothalamic sites at which substituted benzamide drugs act to facilitate gastric emptying in the guinea-pig.

    Science.gov (United States)

    Costall, B; Gunning, S J; Naylor, R J

    1985-09-01

    An analysis of the hypothalamic sites at which the substituted benzamides, metoclopramide and clebopride, act to facilitate gastric emptying was undertaken in the guinea-pig. Standard stereotaxic techniques for intracerebral injection via chronically indwelling intracerebral guides were combined with measurement of gastric emptying by fluoroscopic following of the passage of barium sulphate spheroids from the stomach. Injections were made at 7 different locations within the hypothalamus at Ant. 8.0, 8.9 and 9.6, Lat. +/- 1.0, +/- 1.6, +/- 2.2 (relative to the stereotaxic frame) and at 7.0, 8.0 and 9.0 mm below guide tips in the cortex. The most sensitive sites for gastric facilitation by the substituted benzamides were located at Ant. 8.9, Lat. +/- 1.6, Vert. -8.0, -9.0, the "perifornical area". As the distance of the injection site from the area of the fornix increased, so the facilitatory gastric action diminished, with marked delays or loss in response occurring when injection sites were moved 1 mm above, 0.6 mm lateral, 0.4 mm medial, 0.9 mm posterior or 0.7 mm anterior. The facilitatory gastric actions of metoclopramide and clebopride in the perifornical area of the hypothalamus were not mimicked by haloperidol, domperidone or sulpiride. Atropine, injected into the hypothalamus, markedly reduced gastric emptying; hexamethonium was less effective, and phentolamine, propranolol and methysergide were inactive. Atropine (but not hexamethonium, phentolamine, propranolol or methysergide), injected into the hypothalamus, dose-dependently antagonised the facilitatory gastric action of metoclopramide injected at the same site. Carbachol (but not serotonin, noradrenaline, dopamine or apomorphine), injected into the perifornical area, caused marked facilitation of gastric emptying.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Effects of the antituberculous drug ethambutol on zinc absorption, turnover and distribution in rats fed diet marginal and adequate in zinc

    Energy Technology Data Exchange (ETDEWEB)

    King, A.B.; Schwartz, R.

    1987-04-01

    Ethambutol, (CH/sub 3/CH/sub 2/-CH(CH/sub 2/OH)-NH-CH/sub 2/)/sub 2/ (EMB), is an oral antituberculous agent that is administered therapeutically over extended time periods. It has chelating properties and may affect mineral metabolism. Male weanling Sprague-Dawley rats received 0, 400 or 600 mg EMB per kilogram body weight daily by gavage for 30 d. They were fed a casein-based diet with either adequate (49 ppm) or marginal (11 ppm) zinc. Both adequate-Zn (AZn) and marginal-Zn (MZn) rats receiving EMB showed alopecia and dose-dependent reductions in feed intake, weight gain and feed efficiency. None of these changes was seen in rats fed the MZn diet without EMB. Serum and tissue zinc levels were similar in rats not receiving EMB, regardless of the dietary zinc level. Serum zinc was consistently lower in AZn and MZn rats receiving EMB than in rats without EMB. Apparent zinc absorption, measured by /sup 65/Zn balance, was higher in AZn rats receiving EMB than in AZn rats without EMB. Thus, changes in absorption could not account for lower serum zinc levels in EMB-treated rats. However, /sup 65/Zn turnover was also higher in EMB groups. This suggests that EMB may have increased urinary zinc losses resulting in reduced circulating zinc and a consequent increase in zinc absorption.

  18. Effects of the antituberculous drug ethambutol on zinc absorption, turnover and distribution in rats fed diet marginal and adequate in zinc

    International Nuclear Information System (INIS)

    King, A.B.; Schwartz, R.

    1987-01-01

    Ethambutol, [CH 3 CH 2 -CH(CH 2 OH)-NH-CH 2 ] 2 (EMB), is an oral antituberculous agent that is administered therapeutically over extended time periods. It has chelating properties and may affect mineral metabolism. Male weanling Sprague-Dawley rats received 0, 400 or 600 mg EMB per kilogram body weight daily by gavage for 30 d. They were fed a casein-based diet with either adequate (49 ppm) or marginal (11 ppm) zinc. Both adequate-Zn (AZn) and marginal-Zn (MZn) rats receiving EMB showed alopecia and dose-dependent reductions in feed intake, weight gain and feed efficiency. None of these changes was seen in rats fed the MZn diet without EMB. Serum and tissue zinc levels were similar in rats not receiving EMB, regardless of the dietary zinc level. Serum zinc was consistently lower in AZn and MZn rats receiving EMB than in rats without EMB. Apparent zinc absorption, measured by 65 Zn balance, was higher in AZn rats receiving EMB than in AZn rats without EMB. Thus, changes in absorption could not account for lower serum zinc levels in EMB-treated rats. However, 65 Zn turnover was also higher in EMB groups. This suggests that EMB may have increased urinary zinc losses resulting in reduced circulating zinc and a consequent increase in zinc absorption

  19. Absorptive products

    International Nuclear Information System (INIS)

    Assarsson, P.G.; King, P.A.

    1976-01-01

    Applications for hydrophile gels produced by the radiation induced cross-linking in aqueous solution of polyethylene oxide and starch, as described in Norwegian patent 133501 (INIS RN 281494), such as sanitary napkins (diapers) and sanitary towels, are discussed. The process itself is also discussed and results, expressed as the percentage of insoluble gel and its absorptive capacity for saline solution as functions of the ratio of polyethylene oxide to starch and the radiation dose, are presented. (JIW)

  20. Artificial Lipid Membrane Permeability Method for Predicting Intestinal Drug Transport: Probing the Determining Step in the Oral Absorption of Sulfadiazine; Influence of the Formation of Binary and Ternary Complexes with Cyclodextrins.

    Science.gov (United States)

    Delrivo, Alicia; Aloisio, Carolina; Longhi, Marcela R; Granero, Gladys

    2018-04-01

    We propose an in vitro permeability assay by using a modified lipid membrane to predict the in vivo intestinal passive permeability of drugs. Two conditions were tested, one with a gradient pH (pH 5.5 donor/pH 7.4 receptor) and the other with an iso-pH 7.4. The predictability of the method was established by correlating the obtained apparent intestinal permeability coefficients (P app ) and the oral dose fraction absorbed in humans (f a ) of 16 drugs with different absorption properties. The P app values correlated well with the absorption rates under the two conditions, and the method showed high predictability and good reproducibility. On the other hand, with this method, we successfully predicted the transport characteristics of oral sulfadiazine (SDZ). Also, the tradeoff between the increase in the solubility of SDZ by its complex formation with cyclodextrins and/or aminoacids and its oral permeability was assessed. Results suggest that SDZ is transported through the gastrointestinal epithelium by passive diffusion in a pH-dependent manner. These results support the classification of SDZ as a high/low borderline permeability compound and are in agreement with the Biopharmaceutics Classification Systems (BCS). This conclusion is consistent with the in vivo pharmacokinetic properties of SDZ.

  1. Barriers and facilitators of adherence to antiretroviral drug therapy and retention in care among adult HIV-positive patients: a qualitative study from Ethiopia.

    Directory of Open Access Journals (Sweden)

    Woldesellassie M Bezabhe

    Full Text Available BACKGROUND: Antiretroviral therapy (ART has been life saving for hundreds of thousands of Ethiopians. With increased availability of ART in recent years, achievement of optimal adherence and patient retention are becoming the greatest challenges in the management of HIV/AIDS in Ethiopia. However, few studies have explored factors influencing medication adherence to ART and retention in follow-up care among adult Ethiopian HIV-positive patients, especially in the Amhara region of the country, where almost one-third of the country's ART is prescribed. The aim of this qualitative study was to collect such data from patients and healthcare providers in the Amhara region of Ethiopia. METHODS: Semi-structured interviews were conducted with 24 patients, of whom 11 had been lost to follow-up and were non-persistent with ART. In addition, focus group discussions were performed with 15 ART nurses and 19 case managers. All interviews and focus groups were audio-recorded, transcribed, and coded for themes and patterns in Amharic using a grounded theory approach. The emergent concepts and categories were translated into English. RESULTS: Economic constraints, perceived stigma and discrimination, fasting, holy water, medication side effects, and dissatisfaction with healthcare services were major reasons for patients being non-adherent and lost to follow-up. Disclosure of HIV status, social support, use of reminder aids, responsibility for raising children, improved health on ART, and receiving education and counseling emerged as facilitators of adherence to ART. CONCLUSIONS: Improving adherence and retention requires integration of enhanced treatment access with improved job and food security. Healthcare providers need to be supported to better equip patients to cope with the issues associated with ART. Development of social policies and cooperation between various agencies are required to facilitate optimal adherence to ART, patient retention, and improved

  2. Barriers and facilitators of adherence to antiretroviral drug therapy and retention in care among adult HIV-positive patients: a qualitative study from Ethiopia.

    Science.gov (United States)

    Bezabhe, Woldesellassie M; Chalmers, Leanne; Bereznicki, Luke R; Peterson, Gregory M; Bimirew, Mekides A; Kassie, Desalew M

    2014-01-01

    Antiretroviral therapy (ART) has been life saving for hundreds of thousands of Ethiopians. With increased availability of ART in recent years, achievement of optimal adherence and patient retention are becoming the greatest challenges in the management of HIV/AIDS in Ethiopia. However, few studies have explored factors influencing medication adherence to ART and retention in follow-up care among adult Ethiopian HIV-positive patients, especially in the Amhara region of the country, where almost one-third of the country's ART is prescribed. The aim of this qualitative study was to collect such data from patients and healthcare providers in the Amhara region of Ethiopia. Semi-structured interviews were conducted with 24 patients, of whom 11 had been lost to follow-up and were non-persistent with ART. In addition, focus group discussions were performed with 15 ART nurses and 19 case managers. All interviews and focus groups were audio-recorded, transcribed, and coded for themes and patterns in Amharic using a grounded theory approach. The emergent concepts and categories were translated into English. Economic constraints, perceived stigma and discrimination, fasting, holy water, medication side effects, and dissatisfaction with healthcare services were major reasons for patients being non-adherent and lost to follow-up. Disclosure of HIV status, social support, use of reminder aids, responsibility for raising children, improved health on ART, and receiving education and counseling emerged as facilitators of adherence to ART. Improving adherence and retention requires integration of enhanced treatment access with improved job and food security. Healthcare providers need to be supported to better equip patients to cope with the issues associated with ART. Development of social policies and cooperation between various agencies are required to facilitate optimal adherence to ART, patient retention, and improved patient outcomes.

  3. In Vivo Optical Imaging for Targeted Drug Kinetics and Localization for Oral Surgery and Super-Resolution, Facilitated by Printed Phantoms

    Science.gov (United States)

    Bentz, Brian Z.

    Many human cancer cell types over-express folate receptors, and this provides an opportunity to develop targeted anti-cancer drugs. For these drugs to be effective, their kinetics must be well understood in vivo and in deep tissue where tumors occur. We demonstrate a method for imaging these parameters by incorporating a kinetic compartment model and fluorescence into optical diffusion tomography (ODT). The kinetics were imaged in a live mouse, and found to be in agreement with previous in vitro studies, demonstrating the validity of the method and its feasibility as an effective tool in preclinical drug development studies. Progress in developing optical imaging for biomedical applications requires customizable and often complex objects known as "phantoms" for testing and evaluation. We present new optical phantoms fabricated using inexpensive 3D printing methods with multiple materials, allowing for the placement of complex inhomogeneities in heterogeneous or anatomically realistic geometries, as opposed to previous phantoms which were limited to simple shapes formed by molds or machining. Furthermore, we show that Mie theory can be used to design the optical properties to match a target tissue. The phantom fabrication methods are versatile, can be applied to optical imaging methods besides diffusive imaging, and can be used in the calibration of live animal imaging data. Applications of diffuse optical imaging in the operating theater have been limited in part due to computational burden. We present an approach for the fast localization of arteries in the roof of the mouth that has the potential to reduce complications. Furthermore, we use the extracted position information to fabricate a custom surgical guide using 3D printing that could protect the arteries during surgery. The resolution of ODT is severely limited by the attenuation of high spatial frequencies. We present a super-resolution method achieved through the point localization of fluorescent

  4. Calculation of absorption parameters for selected narcotic drugs in the energy range from 1 keV to 100 GeV

    Science.gov (United States)

    Akman, Ferdi; Kaçal, Mustafa Recep; Akdemir, Fatma; Araz, Aslı; Turhan, Mehmet Fatih; Durak, Rıdvan

    2017-04-01

    The total mass attenuation coefficients (μ/ρ), total molecular (σt,m), atomic (σt,a) and electronic (σt,e) cross sections, effective atomic numbers (Zeff) and electron density (NE) were computed in the wide energy region from 1 keV to 100 GeV for the selected narcotic drugs such as morphine, heroin, cocaine, ecstasy and cannabis. The changes of μ/ρ, σt,m, σt,a, σt,e, Zeff and NE with photon energy for total photon interaction shows the dominance of different interaction process in different energy regions. The variations of μ/ρ, σt,m, σt,a, σt,e, Zeff and NE depend on the atom number, photon energy and chemical composition of narcotic drugs. Also, these parameters change with number of elements, the range of atomic numbers in narcotic drugs and total molecular weight. These data can be useful in the field of forensic sciences and medical diagnostic.

  5. Absorption and Metabolism of Xanthophylls

    Directory of Open Access Journals (Sweden)

    Eiichi Kotake-Nara

    2011-06-01

    Full Text Available Dietary carotenoids, especially xanthophylls, have attracted significant attention because of their characteristic biological activities, including anti-allergic, anti-cancer, and anti-obese actions. Although no less than forty carotenoids are ingested under usual dietary habits, only six carotenoids and their metabolites have been found in human tissues, suggesting selectivity in the intestinal absorption of carotenoids. Recently, facilitated diffusion in addition to simple diffusion has been reported to mediate the intestinal absorption of carotenoids in mammals. The selective absorption of carotenoids may be caused by uptake to the intestinal epithelia by the facilitated diffusion and an unknown excretion to intestinal lumen. It is well known that β-carotene can be metabolized to vitamin A after intestinal absorption of carotenoids, but little is known about the metabolic transformation of non provitamin A xanthophylls. The enzymatic oxidation of the secondary hydroxyl group leading to keto-carotenoids would occur as a common pathway of xanthophyll metabolism in mammals. This paper reviews the absorption and metabolism of xanthophylls by introducing recent advances in this field.

  6. Absorption and metabolism of xanthophylls.

    Science.gov (United States)

    Kotake-Nara, Eiichi; Nagao, Akihiko

    2011-01-01

    Dietary carotenoids, especially xanthophylls, have attracted significant attention because of their characteristic biological activities, including anti-allergic, anti-cancer, and anti-obese actions. Although no less than forty carotenoids are ingested under usual dietary habits, only six carotenoids and their metabolites have been found in human tissues, suggesting selectivity in the intestinal absorption of carotenoids. Recently, facilitated diffusion in addition to simple diffusion has been reported to mediate the intestinal absorption of carotenoids in mammals. The selective absorption of carotenoids may be caused by uptake to the intestinal epithelia by the facilitated diffusion and an unknown excretion to intestinal lumen. It is well known that β-carotene can be metabolized to vitamin A after intestinal absorption of carotenoids, but little is known about the metabolic transformation of non provitamin A xanthophylls. The enzymatic oxidation of the secondary hydroxyl group leading to keto-carotenoids would occur as a common pathway of xanthophyll metabolism in mammals. This paper reviews the absorption and metabolism of xanthophylls by introducing recent advances in this field.

  7. Segmental dependent transport of low permeability compounds along the small intestine due to P-glycoprotein: the role of efflux transport in the oral absorption of BCS class III drugs.

    Science.gov (United States)

    Dahan, Arik; Amidon, Gordon L

    2009-01-01

    The purpose of this study was to investigate the role of P-gp efflux in the in vivo intestinal absorption process of BCS class III P-gp substrates, i.e. high-solubility low-permeability drugs. The in vivo permeability of two H (2)-antagonists, cimetidine and famotidine, was determined by the single-pass intestinal perfusion model in different regions of the rat small intestine, in the presence or absence of the P-gp inhibitor verapamil. The apical to basolateral (AP-BL) and the BL-AP transport of the compounds in the presence or absence of various efflux transporters inhibitors (verapamil, erythromycin, quinidine, MK-571 and fumitremorgin C) was investigated across Caco-2 cell monolayers. P-gp expression levels in the different intestinal segments were confirmed by immunoblotting. Cimetidine and famotidine exhibited segmental dependent permeability through the gut wall, with decreased P(eff) in the distal ileum in comparison to the proximal regions of the intestine. Coperfusion of verapamil with the drugs significantly increased the permeability in the ileum, while no significant change in the jejunal permeability was observed. Both drugs exhibited significantly greater BL-AP than AP-BL Caco-2 permeability, indicative of net mucosal secretion. Concentration dependent decrease of this secretion was obtained by the P-gp inhibitors verapamil, erythromycin and quinidine, while no effect was evident by the MRP2 inhibitor MK-571 and the BCRP inhibitor FTC, indicating that P-gp is the transporter mediates the intestinal efflux of cimetidine and famotidine. P-gp levels throughout the intestine were inversely related to the in vivo permeability of the drugs from the different segments. The data demonstrate that for these high-solubility low-permeability P-gp substrates, P-gp limits in vivo intestinal absorption in the distal segments of the small intestine; however P-gp plays a minimal role in the proximal intestinal segments due to significant lower P-gp expression levels

  8. Evaluation of the use of partition coefficients and molecular surface properties as predictors of drug absorption: a provisional biopharmaceutical classification of the list of national essential medi

    Directory of Open Access Journals (Sweden)

    NU Rahman

    2011-05-01

    Full Text Available Background and the purpose of the study: Partition coefficients (log D and log P and molecular surface area (PSA are potential predictors of the intestinal permeability of drugs. The aim of this investigation was to evaluate and compare these intestinal permeability indicators.   Methods: Aqueous solubility data were obtained from literature or calculated using ACD/Labs and ALOGPS. Permeability data were predicted based on log P, log D at pH 6.0 (log D6.0, and PSA.  Results: Metoprolol's log P, log D6.0 and a PSA of <65 Å correctly predicted 55.9%, 50.8% and 54.2% of permeability classes, respectively. Labetalol's log P, log D6.0, and PSA correctly predicted 54.2%, 64.4% and 61% of permeability classes, respectively. Log D6.0 correlated well (81% with Caco-2 permeability (Papp. Of the list of national essential medicines, 135 orally administered drugs were classified into biopharmaceutical classification system (BCS. Of these, 57 (42.2%, 28 (20.7%, 44 (32.6%, and 6 (4.4% were class I, II, III and IV respectively. Conclusion: Log D6.0 showed better prediction capability than log P. Metoprolol as permeability internal standard was more conservative than labetalol.

  9. Correlates of reasons for not reporting rape to police: results from a national telephone household probability sample of women with forcible or drug-or-alcohol facilitated/incapacitated rape.

    Science.gov (United States)

    Cohn, Amy M; Zinzow, Heidi M; Resnick, Heidi S; Kilpatrick, Dean G

    2013-02-01

    Rape tactics, rape incident characteristics, and mental health problems (lifetime depression, PTSD, and substance abuse) were investigated as correlates of eight different reasons for not reporting a rape to police among women who had experienced but did not report a rape to police (n = 441) within a national telephone household probability sample. Rape tactics (nonmutually exclusive) included drug or alcohol-facilitated or incapacitated rape (DAFR/IR; n = 119) and forcible rape (FR; n = 376). Principal Components Analysis (PCA) was conducted to extract a dominant set of patterns among the eight reasons for not reporting, and to reduce the set of dependent variables. PCA results indicated three unique factors: Not Wanting Others to Know, Nonacknowledgment of Rape, and Criminal Justice Concerns. Hierarchical regression analyses showed DAFR/IR and FR were both positively and significantly associated with Criminal Justice Concerns, whereas DAFR/IR, but not FR, was associated with Nonacknowledgment as a reason for not reporting to police. Neither DAFR/IR nor FR emerged as significant predictors of Others Knowing after controlling for fear of death or injury at the time of the incident. Correlations among variables showed that the Criminal Justice Concerns factor was positively related to lifetime depression and PTSD and the Nonacknowledgement factor was negatively related to lifetime PTSD. Findings suggest prevention programs should educate women about the definition of rape, which may include incapacitation due to alcohol or drugs, to increase acknowledgement and decrease barriers to police reporting.

  10. Iron absorption studies

    International Nuclear Information System (INIS)

    Ekenved, G.

    1976-01-01

    The main objective of the present work was to study iron absorption from different iron preparations in different types of subjects and under varying therapeutic conditions. The studies were performed with different radioiron isotope techniques and with a serum iron technique. The preparations used were solutions of ferrous sulphate and rapidly-disintegrating tablets containing ferrous sulphate, ferrous fumarate and ferrous carbonate and a slow-release ferrous sulphate tablet of an insoluble matrix type (Duroferon Durules). The serum iron method was evaluated and good correlation was found between the serum iron response and the total amount of iron absorbed after an oral dose of iron given in solution or in tablet form. New technique for studying the in-vivo release properties of tablets was presented. Iron tablets labelled with a radio-isotope were given to healthy subjects. The decline of the radioactivity in the tablets was followed by a profile scanning technique applied to different types of iron tablets. The release of iron from the two types of tablets was shown to be slower in vivo than in vitro. It was found that co-administration of antacids and iron tablets led to a marked reduction in the iron absorption and that these drugs should not be administered sumultaneously. A standardized meal markedly decreased the absorbability of iron from iron tablets. The influence of the meal was more marked with rapidly-disintegrating than with slow-release ferrous sulphate tablets. The absorption from rapidly-disintegrating and slow-release ferrous sulphate tablets was compared under practical clinical conditions during an extended treatment period. The studies were performed in healthy subjects, blood donors and patients with iron deficiency anaemia and it was found that the absorption of iron from the slow-release tablets was significantly better than from the rapidly-disintegrating tablets in all three groups of subjects. (author)

  11. pH-sensitive polymeric nanoparticles to improve oral bioavailability of peptide/protein drugs and poorly water-soluble drugs.

    Science.gov (United States)

    Wang, Xue-Qing; Zhang, Qiang

    2012-10-01

    pH-sensitive polymeric nanoparticles are promising for oral drug delivery, especially for peptide/protein drugs and poorly water-soluble medicines. This review describes current status of pH-sensitive polymeric nanoparticles for oral drug delivery and introduces the mechanisms of drug release from them as well as possible reasons for absorption improvement, with emphasis on our contribution to this field. pH-sensitive polymeric nanoparticles are prepared mainly with polyanions, polycations, their mixtures or cross-linked polymers. The mechanisms of drug release are the result of carriers' dissolution, swelling or both of them at specific pH. The possible reasons for improvement of oral bioavailability include the following: improve drug stability, enhance mucoadhesion, prolong resident time in GI tract, ameliorate intestinal permeability and increase saturation solubility and dissolution rate for poorly water-soluble drugs. As for the advantages of pH-sensitive nanoparticles over conventional nanoparticles, we conclude that (1) most carriers used are enteric-coating materials and their safety has been approved. (2) The rapid dissolution or swelling of carriers at specific pH results in quick drug release and high drug concentration gradient, which is helpful for absorption. (3) At the specific pH carriers dissolve or swell, and the bioadhesion of carriers to mucosa becomes high because nanoparticles turn from solid to gel, which can facilitate drug absorption. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Improved oral absorption of tacrolimus by a solid dispersion with hypromellose and sodium lauryl sulfate.

    Science.gov (United States)

    Jung, Hyuck Jun; Ahn, Hye In; Park, Ji Yeon; Ho, Myoung Jin; Lee, Dae Ro; Cho, Ha Ra; Park, Jun Seo; Choi, Yong Seok; Kang, Myung Joo

    2016-02-01

    A novel surfactant-incorporated hydroxypropyl methylcellulose (HPMC) solid dispersion (SD) system was constructed in order to facilitate the release rate and oral absorption of tacrolimus (FK506), a poorly water-soluble immunosuppressant. Several emulsifiers including sodium lauryl sulfate (SLS), as drug release promotors, were employed with HPMC to fabricate SD using the solvent wetting method. The solid state characteristics using differential scanning calorimetry and X-ray powder diffraction, revealed that FK506 was molecularly distributed within all dispersions in amorphous form. The dissolution rates of FK506 in SLS-incorporated SDs were much higher than those in SDs prepared with HPMC alone, and even with stearoyl polyoxyl-32 glycerides or tocopheryl polyethylene glycol 1000 succinate. In particular, the greatest dissolution enhancement was obtained from the SD consisting of the drug, HPMC, and SLS in a weight ratio of 1:1:3, providing a 50-fold higher drug concentration within 15 min, compared with HPMC SD. In vivo absorption study in rats demonstrates that the optimized formula remarkably increased the oral absorption of FK506, providing about 4.0-fold greater bioavailability (p<0.05) compared with the marketed product (Prograf®, Astellas Pharma). These data suggest that a novel SLS/HPMC SD may be an advantageous dosage form of FK506, boosting the dissolution and absorption in gastrointestinal tract. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Pharmacokinetic-Pharmacodynamic (PKPD) Analysis with Drug Discrimination.

    Science.gov (United States)

    Negus, S Stevens; Banks, Matthew L

    2016-08-30

    Discriminative stimulus and other drug effects are determined by the concentration of drug at its target receptor and by the pharmacodynamic consequences of drug-receptor interaction. For in vivo procedures such as drug discrimination, drug concentration at receptors in a given anatomical location (e.g., the brain) is determined both by the dose of drug administered and by pharmacokinetic processes of absorption, distribution, metabolism, and excretion that deliver drug to and from that anatomical location. Drug discrimination data are often analyzed by strategies of dose-effect analysis to determine parameters such as potency and efficacy. Pharmacokinetic-Pharmacodynamic (PKPD) analysis is an alternative to conventional dose-effect analysis, and it relates drug effects to a measure of drug concentration in a body compartment (e.g., venous blood) rather than to drug dose. PKPD analysis can yield insights on pharmacokinetic and pharmacodynamic determinants of drug action. PKPD analysis can also facilitate translational research by identifying species differences in pharmacokinetics and providing a basis for integrating these differences into interpretation of drug effects. Examples are discussed here to illustrate the application of PKPD analysis to the evaluation of drug effects in rhesus monkeys trained to discriminate cocaine from saline.

  14. Slowing down with resonance absorption

    International Nuclear Information System (INIS)

    Moura Neto, C. de; Nair, R.P.K.

    1979-08-01

    The presence of heavy nuclei in nuclear reactors, in significant concentrations, facilitates the appearance of absorption resonances. For the moderation in the presence of absorbers an exact solution of the integral equations is possible by numerical methods. Approximated solutions for separated resonances in function of the practical width, (NR and NRIM approximations) are discussed in this paper. The method is generalized, presenting the solution by an intermediate approximation, in the definition of the resonance integral. (Author) [pt

  15. Absorption and Metabolism of Xanthophylls

    OpenAIRE

    Kotake-Nara, Eiichi; Nagao, Akihiko

    2011-01-01

    Dietary carotenoids, especially xanthophylls, have attracted significant attention because of their characteristic biological activities, including anti-allergic, anti-cancer, and anti-obese actions. Although no less than forty carotenoids are ingested under usual dietary habits, only six carotenoids and their metabolites have been found in human tissues, suggesting selectivity in the intestinal absorption of carotenoids. Recently, facilitated diffusion in addition to simple diffusion has bee...

  16. Low Buffer Capacity and Alternating Motility along the Human Gastrointestinal Tract: Implications for in Vivo Dissolution and Absorption of Ionizable Drugs.

    Science.gov (United States)

    Hens, Bart; Tsume, Yasuhiro; Bermejo, Marival; Paixao, Paulo; Koenigsknecht, Mark J; Baker, Jason R; Hasler, William L; Lionberger, Robert; Fan, Jianghong; Dickens, Joseph; Shedden, Kerby; Wen, Bo; Wysocki, Jeffrey; Loebenberg, Raimar; Lee, Allen; Frances, Ann; Amidon, Greg; Yu, Alex; Benninghoff, Gail; Salehi, Niloufar; Talattof, Arjang; Sun, Duxin; Amidon, Gordon L

    2017-12-04

    In this study, we determined the pH and buffer capacity of human gastrointestinal (GI) fluids (aspirated from the stomach, duodenum, proximal jejunum, and mid/distal jejunum) as a function of time, from 37 healthy subjects after oral administration of an 800 mg immediate-release tablet of ibuprofen (reference listed drug; RLD) under typical prescribed bioequivalence (BE) study protocol conditions in both fasted and fed states (simulated by ingestion of a liquid meal). Simultaneously, motility was continuously monitored using water-perfused manometry. The time to appearance of phase III contractions (i.e., housekeeper wave) was monitored following administration of the ibuprofen tablet. Our results clearly demonstrated the dynamic change in pH as a function of time and, most significantly, the extremely low buffer capacity along the GI tract. The buffer capacity on average was 2.26 μmol/mL/ΔpH in fasted state (range: 0.26 and 6.32 μmol/mL/ΔpH) and 2.66 μmol/mL/ΔpH in fed state (range: 0.78 and 5.98 μmol/mL/ΔpH) throughout the entire upper GI tract (stomach, duodenum, and proximal and mid/distal jejunum). The implication of this very low buffer capacity of the human GI tract is profound for the oral delivery of both acidic and basic active pharmaceutical ingredients (APIs). An in vivo predictive dissolution method would require not only a bicarbonate buffer but also, more significantly, a low buffer capacity of dissolution media to reflect in vivo dissolution conditions.

  17. Systems Pharmacology in Small Molecular Drug Discovery

    Directory of Open Access Journals (Sweden)

    Wei Zhou

    2016-02-01

    Full Text Available Drug discovery is a risky, costly and time-consuming process depending on multidisciplinary methods to create safe and effective medicines. Although considerable progress has been made by high-throughput screening methods in drug design, the cost of developing contemporary approved drugs did not match that in the past decade. The major reason is the late-stage clinical failures in Phases II and III because of the complicated interactions between drug-specific, human body and environmental aspects affecting the safety and efficacy of a drug. There is a growing hope that systems-level consideration may provide a new perspective to overcome such current difficulties of drug discovery and development. The systems pharmacology method emerged as a holistic approach and has attracted more and more attention recently. The applications of systems pharmacology not only provide the pharmacodynamic evaluation and target identification of drug molecules, but also give a systems-level of understanding the interaction mechanism between drugs and complex disease. Therefore, the present review is an attempt to introduce how holistic systems pharmacology that integrated in silico ADME/T (i.e., absorption, distribution, metabolism, excretion and toxicity, target fishing and network pharmacology facilitates the discovery of small molecular drugs at the system level.

  18. Transdermic absorption of Melagenina II

    International Nuclear Information System (INIS)

    Hernandez Gonzalez, I.; Martinez Lopez, B.; Ruiz Pena, M.; Caso Pena, R.

    1997-01-01

    The transdermic absorption of Melagenina II (MII) was evaluated. MII was a labelled with 125I by the yodogen method and purified by column chromatography with Sephadex LH-20 in ethanol: water (7:3). In vitro absorption of ( 125I ) - MII thought human skin was carried out in Keshary-Chien modified diffusion cells. Tape stripping method was applied after 24 hours to evaluate the accumulated activity in dermis and epidermis. In vivo assays were performed in Sprague Dawley rats to analyze absorption of MII until 24 hours after a single application and for five days a low penetrability of the drug while in vivo there were not found blood levels significantly greater than zero , nevertheless and important amount of radioactivity was found in feces and urine. The activity was concentrated mainly in the application site in both models

  19. Automated applications of sandwich-cultured hepatocytes in the evaluation of hepatic drug transport.

    Science.gov (United States)

    Perry, Cassandra H; Smith, William R; St Claire, Robert L; Brouwer, Kenneth R

    2011-04-01

    Predictions of the absorption, distribution, metabolism, excretion, and toxicity of compounds in pharmaceutical development are essential aspects of the drug discovery process. B-CLEAR is an in vitro system that uses sandwich-cultured hepatocytes to evaluate and predict in vivo hepatobiliary disposition (hepatic uptake, biliary excretion, and biliary clearance), transporter-based hepatic drug-drug interactions, and potential drug-induced hepatotoxicity. Automation of predictive technologies is an advantageous and preferred format in drug discovery. In this study, manual and automated studies are investigated and equivalence is demonstrated. In addition, automated applications using model probe substrates and inhibitors to assess the cholestatic potential of drugs and evaluate hepatic drug transport are examined. The successful automation of this technology provides a more reproducible and less labor-intensive approach, reducing potential operator error in complex studies and facilitating technology transfer.

  20. Clinical Pharmacokinetics of Systemically Administered Antileishmanial Drugs

    NARCIS (Netherlands)

    Kip, Anke E; Schellens, Jan H M; Beijnen, Jos H; Dorlo, Thomas P C

    This review describes the pharmacokinetic properties of the systemically administered antileishmanial drugs pentavalent antimony, paromomycin, pentamidine, miltefosine and amphotericin B (AMB), including their absorption, distribution, metabolism and excretion and potential drug-drug interactions.

  1. Evaluation of transporters in drug development: Current status and contemporary issues.

    Science.gov (United States)

    Lee, Sue-Chih; Arya, Vikram; Yang, Xinning; Volpe, Donna A; Zhang, Lei

    2017-07-01

    Transporters govern the access of molecules to cells or their exit from cells, thereby controlling the overall distribution of drugs to their intracellular site of action. Clinically relevant drug-drug interactions mediated by transporters are of increasing interest in drug development. Drug transporters, acting alone or in concert with drug metabolizing enzymes, can play an important role in modulating drug absorption, distribution, metabolism and excretion, thus affecting the pharmacokinetics and/or pharmacodynamics of a drug. The drug interaction guidance documents from regulatory agencies include various decision criteria that may be used to predict the need for in vivo assessment of transporter-mediated drug-drug interactions. Regulatory science research continues to assess the prediction performances of various criteria as well as to examine the strength and limitations of each prediction criterion to foster discussions related to harmonized decision criteria that may be used to facilitate global drug development. This review discusses the role of transporters in drug development with a focus on methodologies in assessing transporter-mediated drug-drug interactions, challenges in both in vitro and in vivo assessments of transporters, and emerging transporter research areas including biomarkers, assessment of tissue concentrations, and effect of diseases on transporters. Published by Elsevier B.V.

  2. D-xylose absorption

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003606.htm D-xylose absorption To use the sharing features on this page, please enable JavaScript. D-xylose absorption is a laboratory test to determine ...

  3. Absorption and excretion tests

    International Nuclear Information System (INIS)

    Berberich, R.

    1988-01-01

    The absorption and excretion of radiopharmaceuticals is still of interest in diagnostic investigations of nuclear medicine. In this paper the most common methods of measuring absorption and excretion are described. The performance of the different tests and their standard values are discussed. More over the basic possibilities of measuring absorption and excretion including the needed measurement equipments are presented. (orig.) [de

  4. Barriers and facilitators of the HIV care continuum in Southern New England for people with drug or alcohol use and living with HIV/AIDS: perspectives of HIV surveillance experts and service providers.

    Science.gov (United States)

    Grau, Lauretta E; Griffiths-Kundishora, Abbie; Heimer, Robert; Hutcheson, Marguerite; Nunn, Amy; Towey, Caitlin; Stopka, Thomas J

    2017-10-02

    Contemporary studies about HIV care continuum (HCC) outcomes within substance using populations primarily focus on individual risk factors rather than provider- or systems-level influences. Over 25% of people living with HIV (PLWH) have substance use disorders that can alter their path through the HCC. As part of a study of HCC outcomes in nine small cities in Southern New England (population 100,000-200,000 and relatively high HIV prevalence particularly among substance users), this qualitative analysis sought to understand public health staff and HIV service providers' perspectives on how substance use may influence HCC outcomes. Interviews with 49 participants, collected between November 2015 and June 2016, were analyzed thematically using a modified social ecological model as the conceptual framework and codes for substance use, HCC barriers and facilitators, successes and failures of initiatives targeting the HCC, and criminal justice issues. Eight themes were identified concerning the impact of substance use on HCC outcomes. At the individual level, these included coping and satisfying basic needs and could influence all HCC steps (i.e., testing, treatment linkage, adherence, and retention, and viral load suppression). The interpersonal level themes included stigma issues and providers' cultural competence and treatment attitudes and primarily influenced treatment linkage, retention, and viral load suppression. These same HCC steps were influenced at the health care systems level by organizations' physical environment and resources as well as intra-/inter-agency communication. Testing and retention were the most likely steps to affect at the policy/society level, and the themes included opposition within an organization or community, and activities with unintended consequences. The most substantial HCC challenges for PLWH with substance use problems included linking and retaining in treatment those with multiple co-morbidities and meeting their basic living

  5. Slow-light enhancement of Beer-Lambert-Bouguer absorption

    DEFF Research Database (Denmark)

    Mortensen, Asger; Xiao, Sanshui

    2007-01-01

    We theoretically show how slow light in an optofluidic environment facilitates enhanced light-matter interactions, by orders of magnitude. The proposed concept provides strong opportunities for improving existing miniaturized chemical absorbance cells for Beer-Lambert-Bouguer absorption measureme......We theoretically show how slow light in an optofluidic environment facilitates enhanced light-matter interactions, by orders of magnitude. The proposed concept provides strong opportunities for improving existing miniaturized chemical absorbance cells for Beer-Lambert-Bouguer absorption...

  6. Absorptive capacity and smart companies

    Directory of Open Access Journals (Sweden)

    Patricia Moro González

    2014-12-01

    .Originality/value: This paper presents a novel integration of various concepts: the concept of absorptive capacity from academic research and strategic consulting associated with the tools of information management. This allows us to develop better management practices by obtaining profit from these investments and facilitating the creation of intelligence inside organizations.

  7. Calcium absorption and achlorhydria

    International Nuclear Information System (INIS)

    Recker, R.R.

    1985-01-01

    Defective absorption of calcium has been thought to exist in patients with achlorhydria. The author compared absorption of calcium in its carbonate form with that in a pH-adjusted citrate form in a group of 11 fasting patients with achlorhydria and in 9 fasting normal subjects. Fractional calcium absorption was measured by a modified double-isotope procedure with 0.25 g of calcium used as the carrier. Mean calcium absorption (+/- S.D.) in the patients with achlorhydria was 0.452 +/- 0.125 for citrate and 0.042 +/- 0.021 for carbonate (P less than 0.0001). Fractional calcium absorption in the normal subjects was 0.243 +/- 0.049 for citrate and 0.225 +/- 0.108 for carbonate (not significant). Absorption of calcium from carbonate in patients with achlorhydria was significantly lower than in the normal subjects and was lower than absorption from citrate in either group; absorption from citrate in those with achlorhydria was significantly higher than in the normal subjects, as well as higher than absorption from carbonate in either group. Administration of calcium carbonate as part of a normal breakfast resulted in completely normal absorption in the achlorhydric subjects. These results indicate that calcium absorption from carbonate is impaired in achlorhydria under fasting conditions. Since achlorhydria is common in older persons, calcium carbonate may not be the ideal dietary supplement

  8. Visual explorer facilitator's guide

    CERN Document Server

    Palus, Charles J

    2010-01-01

    Grounded in research and practice, the Visual Explorer™ Facilitator's Guide provides a method for supporting collaborative, creative conversations about complex issues through the power of images. The guide is available as a component in the Visual Explorer Facilitator's Letter-sized Set, Visual Explorer Facilitator's Post card-sized Set, Visual Explorer Playing Card-sized Set, and is also available as a stand-alone title for purchase to assist multiple tool users in an organization.

  9. Learning facilitating leadership

    DEFF Research Database (Denmark)

    Rasmussen, Lauge Baungaard; Hansen, Mette Sanne

    2016-01-01

    This paper explains how engineering students at a Danish university acquired the necessary skills to become emergent facilitators of organisational development. The implications of this approach are discussed and related to relevant viewpoints and findings in the literature. The methodology deplo....... By connecting the literature, the authors’ and engineering students’ reflections on facilitator skills, this paper adds value to existing academic and practical discussions on learning facilitating leadership....

  10. Organizational forms and knowledge absorption

    Directory of Open Access Journals (Sweden)

    Radovanović Nikola

    2016-01-01

    Full Text Available Managing the entire portion of knowledge in an organization is a challenging task. At the organizational level, there can be enormous quantities of unknown, poorly valued or inefficiently applied knowledge. This is normally followed with the underdeveloped potential or inability of organizations to absorb knowledge from external sources. Facilitation of the efficient internal flow of knowledge within the established communication network may positively affect organizational capacity to absorb or identify, share and subsequently apply knowledge to commercial ends. Based on the evidences that the adoption of different organizational forms affects knowledge flows within an organization, this research analyzed the relationship between common organizational forms and absorptive capacity of organizations. In this paper, we test the hypothesis stating that the organizational structure affects knowledge absorption and exploitation in the organization. The methodology included quantitative and qualitative research method based on a questionnaire, while the data has been statistically analyzed and the hypothesis has been tested with the use of cross-tabulation and chi-square tests. The findings suggest that the type of organizational form affects knowledge absorption capacity and that having a less formalized and more flexible structure in an organization increases absorbing and exploiting opportunities of potentially valuable knowledge.

  11. [Study on lead absorption in pumpkin by atomic absorption spectrophotometry].

    Science.gov (United States)

    Li, Zhen-Xia; Sun, Yong-Dong; Chen, Bi-Hua; Li, Xin-Zheng

    2008-07-01

    A study was carried out on the characteristic of lead absorption in pumpkin via atomic absorption spectrophotometer. The results showed that lead absorption amount in pumpkin increased with time, but the absorption rate decreased with time; And the lead absorption amount reached the peak in pH 7. Lead and cadmium have similar characteristic of absorption in pumpkin.

  12. Containers, facilitators, innovators?

    DEFF Research Database (Denmark)

    Makkonen, Teemu; Merisalo, Maria; Inkinen, Tommi

    2018-01-01

    : are they containers, facilitators or innovators? This is investigated here through empirical material derived from 27 interviews with top departmental management in three Finnish cities (Helsinki, Espoo and Vantaa). The results show that local city governments (LCGs) consider cities as facilitators of innovation...

  13. Training facilitators and supervisors

    DEFF Research Database (Denmark)

    Kjær, Louise Binow; O Connor, Maja; Krogh, Kristian

    At the Master’s program in Medicine at Aarhus University, Denmark, we have developed a faculty development program for facilitators and supervisors in 4 progressing student modules in communication, cooperation, and leadership. 1) A course for module 1 and 3 facilitators inspired by the apprentic...

  14. Absorption heat pumps

    International Nuclear Information System (INIS)

    Formigoni, C.

    1998-01-01

    A brief description of the difference between a compression and an absorption heat pump is made, and the reasons why absorption systems have spread lately are given. Studies and projects recently started in the field of absorption heat pumps, as well as criteria usually followed in project development are described. An outline (performance targets, basic components) of a project on a water/air absorption heat pump, running on natural gas or LPG, is given. The project was developed by the Robur Group as an evolution of a water absorption refrigerator operating with a water/ammonia solution, which has been on the market for a long time and recently innovated. Finally, a list of the main energy and cost advantages deriving from the use of absorption heat pumps is made [it

  15. Modulation of intestinal absorption of calcium

    Energy Technology Data Exchange (ETDEWEB)

    Fournier, P; Dupuis, Y [Ecole Pratique des Hautes Etudes, 75 - Paris (France); Paris-11 Univ., 92 - Chatenay-Malabry (France))

    1975-01-01

    Absorption of ingested calcium (2ml of a 10mM CaCl/sub 2/ solution + /sup 45/Ca) by the adult rat was shown to be facilitated by the simultaneous ingestion of an active carbohydrate, L-arabinose. As the carbohydrate concentration is increased from 10 to 200mM, the absorption of calcium is maximised at a level corresponding to about twice the control absorption level. A similar doubling of calcium absorption is obtained when a 100mM concentration of any one of a number of other carbohydrates is ingested simultaneously with a 10mM CaCl/sub 2/ solution. Conversely, the simultaneous ingestion of increasing doses (10 to 100mM) of phosphate (NaH/sub 2/PO/sub 4/) with a 10mM CaCl/sub 2/ solution results in decreased /sup 45/Ca absorption and retention by the adult rat. The maximum inhibition of calcium absorption by phosphate is independent of the concentration of the ingested calcium solution (from 5 to 50mM CaCl/sub 2/). The simultaneous ingestion of CaCl/sub 2/ (10mM) with lactose and sodium phosphate (50 and 10mM respectively) shows that the activation effect of lactose upon /sup 45/Ca absorption may be partly dissimulated by the presence of phosphate. These various observations indicate that, within a large concentration range (2 to 50mM CaCl/sub 2/) calcium absorption appears to be a precisely modulated diffusion process. Calcium absorption varies (between minimum and maximum levels) as a function of the state of saturation by the activators (carbohydrates) and inhibitors (phosphate) of the calcium transport system.

  16. Absorption mechanism of three curcumin constituents through in situ intestinal perfusion method

    Directory of Open Access Journals (Sweden)

    Y.-H. Wang

    2017-09-01

    Full Text Available This study aimed to investigate the absorption mechanism of three curcumin constituents in rat small intestines. Self-emulsification was used to solubilize the three curcumin constituents, and the rat in situ intestinal perfusion method was used to study factors on drug absorption, including drug mass concentration, absorption site, and the different types and concentrations of absorption inhibitors. Within the scope of experimental concentrations, three curcumin constituents were absorbed in rat small intestines through the active transport mechanism.

  17. MNC Knowledge Transfer, Subsidiary Absorptive Capacity and HRM

    DEFF Research Database (Denmark)

    Minbaeva, Dana; Pedersen, Torben; Björkman, Ingmar

    2014-01-01

    Based on a sample of 169 subsidiaries of multinational corporations (MNCs) operating in the USA, Russia, and Finland, this paper investigates the relationship between MNC subsidiary HRM practices, absorptive capacity and knowledge transfer. First, we examine the relationship between the application...... of specific HRM practices and the level of the absorptive capacity. Second, we suggest that absorptive capacity should be conceptualized as being comprised of both employees’ ability and motivation. Further, results indicate that both ability and motivation (absorptive capacity) are needed to facilitate...

  18. Solar absorption surface panel

    Science.gov (United States)

    Santala, Teuvo J.

    1978-01-01

    A composite metal of aluminum and nickel is used to form an economical solar absorption surface for a collector plate wherein an intermetallic compound of the aluminum and nickel provides a surface morphology with high absorptance and relatively low infrared emittance along with good durability.

  19. Nutrition and magnesium absorption

    NARCIS (Netherlands)

    Brink, E.J.

    1992-01-01

    The influence of various nutrients present in dairy products and soybean-based products on absorption of magnesium has been investigated. The studies demonstrate that soybean protein versus casein lowers apparent magnesium absorption in rats through its phytate component. However, true

  20. Zeeman atomic absorption spectroscopy

    International Nuclear Information System (INIS)

    Loos-Vollebregt, M.T.C. de.

    1980-01-01

    A new method of background correction in atomic absorption spectroscopy has recently been introduced, based on the Zeeman splitting of spectral lines in a magnetic field. A theoretical analysis of the background correction capability observed in such instruments is presented. A Zeeman atomic absorption spectrometer utilizing a 50 Hz sine wave modulated magnetic field is described. (Auth.)

  1. Effect of food and acid-reducing agents on the absorption of oral targeted therapies in solid tumors

    NARCIS (Netherlands)

    Willemsen, A.E.C.A.B.; Lubberman, F.J.E.; Tol, J.; Gerritsen, W.R.; Herpen, C.M.L. van; Erp, N. van

    2016-01-01

    Oral targeted therapies represent an increasingly important group of drugs within modern oncology. With the shift from intravenously to orally administered drugs, drug absorption is a newly introduced factor in drug disposition. The process of absorption can have a large effect on inter- and

  2. Quasar Absorption Studies

    Science.gov (United States)

    Mushotzky, Richard (Technical Monitor); Elvis, Martin

    2004-01-01

    The aim of the proposal is to investigate the absorption properties of a sample of inter-mediate redshift quasars. The main goals of the project are: Measure the redshift and the column density of the X-ray absorbers; test the correlation between absorption and redshift suggested by ROSAT and ASCA data; constrain the absorber ionization status and metallicity; constrain the absorber dust content and composition through the comparison between the amount of X-ray absorption and optical dust extinction. Unanticipated low energy cut-offs where discovered in ROSAT spectra of quasars and confirmed by ASCA, BeppoSAX and Chandra. In most cases it was not possible to constrain adequately the redshift of the absorber from the X-ray data alone. Two possibilities remain open: a) absorption at the quasar redshift; and b) intervening absorption. The evidences in favour of intrinsic absorption are all indirect. Sensitive XMM observations can discriminate between these different scenarios. If the absorption is at the quasar redshift we can study whether the quasar environment evolves with the Cosmic time.

  3. Impact of pharmaceutical cocrystals: the effects on drug pharmacokinetics.

    Science.gov (United States)

    Shan, Ning; Perry, Miranda L; Weyna, David R; Zaworotko, Michael J

    2014-09-01

    Pharmaceutical cocrystallization has emerged in the past decade as a new strategy to enhance the clinical performance of orally administered drugs. A pharmaceutical cocrystal is a multi-component crystalline material in which the active pharmaceutical ingredient is in a stoichiometric ratio with a second compound that is generally a solid under ambient conditions. The resulting cocrystal exhibits different solid-state thermodynamics, leading to changes in physicochemical properties that offer the potential to significantly modify drug pharmacokinetics. The impact of cocrystallization upon drug pharmacokinetics has not yet been well delineated. Herein, we compile previously published data to address two salient questions: what effect does cocrystallization impart upon physicochemical properties of a drug substance and to what degree can those effects impact its pharmacokinetics. Cocrystals can impact various aspects of drug pharmacokinetics, including, but not limited to, drug absorption. The diversity of solid forms offered through cocrystallization can facilitate drastic changes in solubility and pharmacokinetics. Therefore, it is unsurprising that cocrystal screening is now a routine step in early-stage drug development. With the increasing recognition of pharmaceutical cocrystals from clinical, regulatory and legal perspectives, the systematic commercialization of cocrystal containing drug products is just a matter of time.

  4. Uranium absorption study pile

    International Nuclear Information System (INIS)

    Raievski, V.; Sautiez, B.

    1959-01-01

    The report describes a pile designed to measure the absorption of fuel slugs. The pile is of graphite and comprises a central section composed of uranium rods in a regular lattice. RaBe sources and BF 3 counters are situated on either side of the center. A given uranium charge is compared with a specimen charge of about 560 kg, and the difference in absorption between the two noted. The sensitivity of the equipment will detect absorption variations of about a few ppm boron (10 -6 boron per gr. of uranium) or better. (author) [fr

  5. Total photon absorption

    International Nuclear Information System (INIS)

    Carlos, P.

    1985-06-01

    The present discussion is limited to a presentation of the most recent total photonuclear absorption experiments performed with real photons at intermediate energy, and more precisely in the region of nucleon resonances. The main sources of real photons are briefly reviewed and the experimental procedures used for total photonuclear absorption cross section measurements. The main results obtained below 140 MeV photon energy as well as above 2 GeV are recalled. The experimental study of total photonuclear absorption in the nuclear resonance region (140 MeV< E<2 GeV) is still at its beginning and some results are presented

  6. Coal export facilitation

    International Nuclear Information System (INIS)

    Eeles, L.

    1998-01-01

    There is a wide range of trade barriers, particularly tariffs, in current and potential coal market. Commonwealth departments in Australia play a crucial role in supporting government industry policies. This article summarises some of more recent activities of the Department of Primary Industries and Energy (DPIE) in facilitating the export of Australian Coals. Coal export facilitation activities are designed to assist the Australian coal industry by directing Commonwealth Government resources towards issues which would be inappropriate or difficult for the industry to address itself

  7. ORAL COLON TARGETED DRUG DELIVERY SYSTEM: A REVIEW ON CURRENT AND NOVEL PERSPECTIVES

    OpenAIRE

    Asija Rajesh; Chaudhari Bharat; Asija Sangeeta

    2012-01-01

    Small intestine is mostly the site for drug absorption but in some cases the drug needs to be targeted to colon due to some factors like local colonic disease, degradation related conditions, delayed release of drugs, systemic delivery of protein and peptide drugs etc. Colon targeted drug delivery is important and relatively new concept for the absorption of drugs because it offers almost neutral pH and long residence time, thereby increasing the drug absorption. Colon has proved to be a site...

  8. Absorption heat pump system

    Science.gov (United States)

    Grossman, G.

    1982-06-16

    The efficiency of an absorption heat pump system is improved by conducting liquid from a second stage evaporator thereof to an auxiliary heat exchanger positioned downstream of a primary heat exchanger in the desorber of the system.

  9. Zeeman atomic absorption spectrometry

    International Nuclear Information System (INIS)

    Hadeishi, T.; McLaughlin, R.

    1978-08-01

    The design and development of a Zeeman atomic absorption spectrometer for trace element analysis are described. An instruction manual is included which details the operation, adjustment, and maintenance. Specifications and circuit diagrams are given

  10. Revisiting Absorptive Capacity

    DEFF Research Database (Denmark)

    de Araújo, Ana Luiza Lara; Ulhøi, John Parm; Lettl, Christopher

    Absorptive capacity has mostly been perceived as a 'passive' outcome of R&D investments. Recently, however, a growing interest into its 'proactive' potentials has emerged. This paper taps into this development and proposes a dynamic model for conceptualizing the determinants of the complementary...... learning processes of absorptive capacity, which comprise combinative and adaptive capabilities. Drawing on survey data (n=169), the study concludes that combinative capabilities primarily enhance transformative and exploratory learning processes, while adaptive capabilities strengthen all three learning...

  11. Comment on resonant absorption

    International Nuclear Information System (INIS)

    Hammerling, P.

    1977-01-01

    An average over angles of incidence of the usual resonant absorption function is presented. This form is appropriate under experimental conditions where the angles of incidence vary greatly and in an unknown manner. For comparison a lens-ellipsoidal mirror illumination system with a known longitudinal aberration is considered. In the latter example the angles of incidence are readily obtained and the resulting resonance absorption function evaluated. The associated fields are calculated in a similar fashion. (author)

  12. Optical absorption measurement system

    International Nuclear Information System (INIS)

    Draggoo, V.G.; Morton, R.G.; Sawicki, R.H.; Bissinger, H.D.

    1989-01-01

    This patent describes a non-intrusive method for measuring the temperature rise of optical elements under high laser power optical loading to determine the absorption coefficient. The method comprises irradiating the optical element with a high average power laser beam, viewing the optical element with an infrared camera to determine the temperature across the optical element and calculating the absorption of the optical element from the temperature

  13. Asexual sporulation facilitates adaptation

    NARCIS (Netherlands)

    Zhang, Jianhua; Debets, A.J.M.; Verweij, P.E.; Melchers, W.J.G.; Zwaan, B.J.; Schoustra, S.E.

    2015-01-01

    Understanding the occurrence and spread of azole resistance in Aspergillus fumigatus is crucial for public health. It has been hypothesized that asexual sporulation, which is abundant in nature, is essential for phenotypic expression of azole resistance mutations in A. fumigatus facilitating

  14. Facilitators in Ambivalence

    Science.gov (United States)

    Karlsson, Mikael R.; Erlandson, Peter

    2018-01-01

    This is part of a larger ethnographical study concerning how school development in a local educational context sets cultural and social life in motion. The main data "in this article" consists of semi-structural interviews with teachers (facilitators) who have the responsibility of carrying out a project about formative assessment in…

  15. Facilitation of Adult Development

    Science.gov (United States)

    Boydell, Tom

    2016-01-01

    Taking an autobiographical approach, I tell the story of my experiences facilitating adult development, in a polytechnic and as a management consultant. I relate these to a developmental framework of Modes of Being and Learning that I created and elaborated with colleagues. I connect this picture with a number of related models, theories,…

  16. From Teaching to Facilitation

    DEFF Research Database (Denmark)

    de Graaff, Erik

    2013-01-01

    A shift from teaching to learning is characteristic of the introduction of Problem Based Learning (PBL) in an existing school. As a consequence the teaching staff has to be trained in skills like facilitating group work and writing cases. Most importantly a change in thinking about teaching...

  17. Trade Facilitation in Ethiopia:

    African Journals Online (AJOL)

    Tilahun_EK

    so doing, it attempts to examine how Ethiopia's WTO Accession and trade facilitation ... the more expensive imports, exports and production becomes rendering. Ethiopian ..... can reserve the right to refuse requests of importers for the fifth valuation method to ..... units may find it easier to deal with post clearance audit. In the ...

  18. Dynamics of water absorption through superabsorbent polymer

    Science.gov (United States)

    Chang, Sooyoung; Kim, Wonjung

    2017-11-01

    Superabsorbent polymers (SAPs) consist of hydrophilic cross-linked polymer networks that can absorb and retain a great amount of water relative to their own mass, so that they are widely used for disposable diapers and holding soil moisture in agriculture. SAPs are typically available in the form of submillimeter-sized particles, and the water absorption is driven by capillary flows between particles as well as diffusion that entail swelling. Although the control of water absorption of SAPs is important in engineering applications, but the dynamics of water absorption in SAP particles has not been fully understood. We examine the dynamics of the water absorption of sodium polyacrylate, one of the most common SAP. We experimentally measured the water absorption of sodium polyacrylate particles in one-dimensional confined channel. The water flows through the particles were analyzed by capillarity dominant at the early stage and by diffusion involving volume expansion critical at a later stage. The results provide a quantitative basis of the hydrodynamic analysis of the water flow through SAP particles from a macroscopic point of view, facilitating the prediction of water uptake of SAPs in hygienic and agricultural applications. This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIP) (No.2015R1A2A2A04006181).

  19. [The percutaneous absorption of diclofenac].

    Science.gov (United States)

    Riess, W; Schmid, K; Botta, L; Kobayashi, K; Moppert, J; Schneider, W; Sioufi, A; Strusberg, A; Tomasi, M

    1986-07-01

    The percutaneous absorption of diclofenac diethylammonium 1.16% (w/w) in a combination of emulsion cream and gel (Voltaren Emulgel) and of diclofenac sodium 1% (w/w) in a cream formulation (Voltaren cream) was investigated in guinea-pig, rabbit and man. The percutaneous absorption of diclofenac sodium in guinea-pig was 3 to 6% of the dose when the cream formulation in doses of 320, 100 or 40 mg was applied on 10 cm2 of occluded skin and left in place for 6 h. The transdermal delivery of 14C-labelled diclofenac yielded plateau plasma concentrations of radiotracer from 1.5 h after application until removal of the residual cream. Subsequently the steady state drug depots in the skin and muscle tissue were depleted promptly. During daily administration the steady state levels in the muscle tissue in proximity to the application site were about 3 times higher than in distant muscle tissue. By topical application on knee joints of rabbits diclofenac penetrated into the patellar ligament, the adipose corpus and the synovial fluid. In man the percutaneous absorption was 6% of the dose when the Emulgel formulation was spread by 5 mg/cm2 and left for 12 h on non-occluded skin. The pattern of metabolites of diclofenac in human urine was the same after topical and oral administration. In man, upon daily topical administration of 3 times 2.5 g cream formulation (10 mg/cm2) the diclofenac steady state plasma levels were 20 to 40 nmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Nasal Absorption of Macromolecules from Powder Formulations and Effects of Sodium Carboxymethyl Cellulose on Their Absorption.

    Directory of Open Access Journals (Sweden)

    Akiko Tanaka

    Full Text Available The nasal absorption of macromolecules from powder formulations and the effect of sodium carboxymethyl cellulose (CMC-Na as a pharmaceutical excipient on their absorption were studied. Model macromolecules were fluorescein isothiocyanate-labeled dextran (average molecular weight of 4.4kDa, FD4 and insulin. The plasma concentration of FD4 after application of the powder containing 50% starch (control was higher than that after application of the solution, and the absorption from 50% starch powder was enhanced by the substitution of starch with CMC-Na. The fractional absorption of FD4 after administration of the CMC-Na powder formulation was 30% and 40% higher than that after administration from the solution and the starch powder, respectively. The nasal absorption of insulin from the powder and the effect of CMC-Na were similar with those of FD4. The effective absorption of FD4 and insulin after application of powder with CMC-Na could be due to the increase in the nasal residence of FD4 and insulin. No damage in the nasal mucosa or dysfunction of the mucociliary clearance was observed after application of the drug powder and CMC-Na. The present findings indicate that nasal delivery of powder formulations with the addition of CMC-Na as an excipient is a promising approach for improving the nasal absorption of macromolecules.

  1. Laser facilitates vaccination

    Directory of Open Access Journals (Sweden)

    Ji Wang

    2016-01-01

    Full Text Available Development of novel vaccine deliveries and vaccine adjuvants is of great importance to address the dilemma that the vaccine field faces: to improve vaccine efficacy without compromising safety. Harnessing the specific effects of laser on biological systems, a number of novel concepts have been proposed and proved in recent years to facilitate vaccination in a safer and more efficient way. The key advantage of using laser technology in vaccine delivery and adjuvantation is that all processes are initiated by physical effects with no foreign chemicals administered into the body. Here, we review the recent advances in using laser technology to facilitate vaccine delivery and augment vaccine efficacy as well as the underlying mechanisms.

  2. Facilitating Learning at Conferences

    DEFF Research Database (Denmark)

    Ravn, Ib; Elsborg, Steen

    2011-01-01

    The typical conference consists of a series of PowerPoint presentations that tend to render participants passive. Students of learning have long abandoned the transfer model that underlies such one-way communication. We propose an al-ternative theory of conferences that sees them as a forum...... for learning, mutual inspiration and human flourishing. We offer five design principles that specify how conferences may engage participants more and hence increase their learning. In the research-and-development effort reported here, our team collaborated with conference organizers in Denmark to introduce...... and facilitate a variety of simple learning techniques at thirty one- and two-day conferences of up to 300 participants each. We present ten of these techniques and data evaluating them. We conclude that if conference organizers allocate a fraction of the total conference time to facilitated processes...

  3. Mindfulness for group facilitation

    DEFF Research Database (Denmark)

    Adriansen, Hanne Kirstine; Krohn, Simon

    2014-01-01

    In this paper, we argue that mindfulness techniques can be used for enhancing the outcome of group performance. The word mindfulness has different connotations in the academic literature. Broadly speaking there is ‘mindfulness without meditation’ or ‘Western’ mindfulness which involves active...... thinking and ‘Eastern’ mindfulness which refers to an open, accepting state of mind, as intended with Buddhist-inspired techniques such as meditation. In this paper, we are interested in the latter type of mindfulness and demonstrate how Eastern mindfulness techniques can be used as a tool for facilitation....... A brief introduction to the physiology and philosophy of Eastern mindfulness constitutes the basis for the arguments of the effect of mindfulness techniques. The use of mindfulness techniques for group facilitation is novel as it changes the focus from individuals’ mindfulness practice...

  4. Vitamin A absorption

    International Nuclear Information System (INIS)

    Baker, S.J.

    1976-01-01

    Investigation of the absorption of vitamin A and related substances is complicated by the multiplicity of forms in which they occur in the diet and by the possibility that they may be subject to different mechanisms of absorption. Present knowledge of these mechanisms is inadequate, especially in the case of carotenoids. Numerous tests of absorption have been developed. The most common has been the biochemical measurement of the rise in plasma vitamin A after an oral dose of retinol or retinyl ester, but standardization is inadequate. Radioisotope tests based upon assay of serum or faecal activity following oral administration of tritiated vitamin A derivaties hold considerable promise, but again standardization is inadequate. From investigations hitherto performed it is known that absorption of vitamin A is influenced by several diseases, although as yet the consistency of results and the correlation with other tests of intestinal function have often been poor. However, the test of vitamin A absorption is nevertheless of clinical importance as a specialized measure of intestinal function. (author)

  5. 21 CFR 862.2850 - Atomic absorption spectrophotometer for clinical use.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Atomic absorption spectrophotometer for clinical... Laboratory Instruments § 862.2850 Atomic absorption spectrophotometer for clinical use. (a) Identification. An atomic absorption spectrophotometer for clinical use is a device intended to identify and measure...

  6. Transporter-Guided Delivery of Nanoparticles to Improve Drug Permeation across Cellular Barriers and Drug Exposure to Selective Cell Types

    Directory of Open Access Journals (Sweden)

    Longfa Kou

    2018-01-01

    Full Text Available Targeted nano-drug delivery systems conjugated with specific ligands to target selective cell-surface receptors or transporters could enhance the efficacy of drug delivery and therapy. Transporters are expressed differentially on the cell-surface of different cell types, and also specific transporters are expressed at higher than normal levels in selective cell types under pathological conditions. They also play a key role in intestinal absorption, delivery via non-oral routes (e.g., pulmonary route and nasal route, and transfer across biological barriers (e.g., blood–brain barrier and blood–retinal barrier. As such, the cell-surface transporters represent ideal targets for nano-drug delivery systems to facilitate drug delivery to selective cell types under normal or pathological conditions and also to avoid off-target adverse side effects of the drugs. There is increasing evidence in recent years supporting the utility of cell-surface transporters in the field of nano-drug delivery to increase oral bioavailability, to improve transfer across the blood–brain barrier, and to enhance delivery of therapeutics in a cell-type selective manner in disease states. Here we provide a comprehensive review of recent advancements in this interesting and important area. We also highlight certain key aspects that need to be taken into account for optimal development of transporter-assisted nano-drug delivery systems.

  7. Drug Facts

    Medline Plus

    Full Text Available ... Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug ... Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug ...

  8. [Drugs in pregnancy].

    Science.gov (United States)

    Danchev, N; Astrug, A; Tsankova, V; Nikolova, I

    2006-01-01

    The use of drugs in pregnancy is being discussed. The influence of different factors, both physiological and drug related (physicochemical characteristics, dose, duration of pharmacotherapy) on the processes of absorption, distribution, protein binding, metabolism and excretion are reviewed. The up-to-date classification of the drugs in relation to their effects on the fetus is presented. Special emphasize is given to drugs (antibiotics, cardio-vascular, psychotropic etc.) used for the treatment of acute and chronic conditions in the course of pregnancy. Drugs used for symptoms like pain, high temperature and constipation are also reviewed. Recommendations for the use of safer drugs in pregnancy are given. Drugs with proven teratogenic effects are presented.

  9. Facilitation as a teaching strategy : experiences of facilitators

    Directory of Open Access Journals (Sweden)

    E Lekalakala-Mokgele

    2006-09-01

    Full Text Available Changes in nursing education involve the move from traditional teaching approaches that are teacher-centred to facilitation, a student centred approach. The studentcentred approach is based on a philosophy of teaching and learning that puts the learner on centre-stage. The aim of this study was to identify the challenges of facilitators of learning using facilitation as a teaching method and recommend strategies for their (facilitators development and support. A qualitative, explorative and contextual design was used. Four (4 universities in South Africa which utilize facilitation as a teaching/ learning process were identified and the facilitators were selected to be the sample of the study. The main question posed during in-depth group interviews was: How do you experience facilitation as a teaching/learning method?. Facilitators indicated different experiences and emotions when they first had to facilitate learning. All of them indicated that it was difficult to facilitate at the beginning as they were trained to lecture and that no format for facilitation was available. They experienced frustrations and anxieties as a result. The lack of knowledge of facilitation instilled fear in them. However they indicated that facilitation had many benefits for them and for the students. Amongst the ones mentioned were personal and professional growth. Challenges mentioned were the fear that they waste time and that they do not cover the content. It is therefore important that facilitation be included in the training of nurse educators.

  10. Essence: Facilitating Software Innovation

    DEFF Research Database (Denmark)

    Aaen, Ivan

    2008-01-01

      This paper suggests ways to facilitate creativity and innovation in software development. The paper applies four perspectives – Product, Project, Process, and People –to identify an outlook for software innovation. The paper then describes a new facility–Software Innovation Research Lab (SIRL......) – and a new method concept for software innovation – Essence – based on views, modes, and team roles. Finally, the paper reports from an early experiment using SIRL and Essence and identifies further research....

  11. Physiologically Based Pharmacokinetic and Absorption Modeling for Osmotic Pump Products.

    Science.gov (United States)

    Ni, Zhanglin; Talattof, Arjang; Fan, Jianghong; Tsakalozou, Eleftheria; Sharan, Satish; Sun, Dajun; Wen, Hong; Zhao, Liang; Zhang, Xinyuan

    2017-07-01

    Physiologically based pharmacokinetic (PBPK) and absorption modeling approaches were employed for oral extended-release (ER) drug products based on an osmotic drug delivery system (osmotic pumps). The purpose was to systemically evaluate the in vivo relevance of in vitro dissolution for this type of formulation. As expected, in vitro dissolution appeared to be generally predictive of in vivo PK profiles, because of the unique feature of this delivery system that the in vitro and in vivo release of osmotic pump drug products is less susceptible to surrounding environment in the gastrointestinal (GI) tract such as pH, hydrodynamic, and food effects. The present study considered BCS (Biopharmaceutics Classification System) class 1, 2, and 3 drug products with half-lives ranging from 2 to greater than 24 h. In some cases, the colonic absorption models needed to be adjusted to account for absorption in the colon. C max (maximum plasma concentration) and AUCt (area under the concentration curve) of the studied drug products were sensitive to changes in colon permeability and segmental GI transit times in a drug product-dependent manner. While improvement of the methodology is still warranted for more precise prediction (e.g., colonic absorption and dynamic movement in the GI tract), the results from the present study further emphasized the advantage of using PBPK modeling in addressing product-specific questions arising from regulatory review and drug development.

  12. Understanding the Oral Mucosal Absorption and Resulting Clinical Pharmacokinetics of Asenapine

    NARCIS (Netherlands)

    Bartlett, Jeremy A.; Maarschalk, Kees van der Voort

    2012-01-01

    Absorption of drugs from the oral cavity into the mucosal tissues is typically a fast event. Dissolved drugs partition into the mucosal membranes and within minutes will reach equilibrium with drug in solution in the oral cavity. However, this does not always equate to rapid drug appearance in the

  13. Neutron resonance absorption theory

    International Nuclear Information System (INIS)

    Reuss, P.

    1991-11-01

    After some recalls on the physics of neutron resonance absorption during their slowing down, this paper presents the main features of the theoretical developments performed by the french school of reactor physics: the effective reaction rate method so called Livolant-Jeanpierre theory, the generalizations carried out by the author, and the probability table method [fr

  14. Noble gas absorption process

    International Nuclear Information System (INIS)

    Thomas, J.W.

    1975-01-01

    A method of removing a noble gas from air comprising the use of activated carbon filters in stages in which absorption and desorption steps in succession are conducted in order to increase the capacity of the filters is described. (U.S.)

  15. Total photon absorption

    International Nuclear Information System (INIS)

    Carlos, P.

    1985-01-01

    Experimental methods using real photon beams for measurements of total photonuclear absorption cross section σ(Tot : E/sub γ/) are recalled. Most recent σ(Tot : E/sub γ/)results for complex nuclei and in the nucleon resonance region are presented

  16. Chemical Absorption Materials

    DEFF Research Database (Denmark)

    Thomsen, Kaj

    2011-01-01

    Chemical absorption materials that potentially can be used for post combustion carbon dioxide capture are discussed. They fall into five groups, alkanolamines, alkali carbonates, ammonia, amino acid salts, and ionic liquids. The chemistry of the materials is discussed and advantages and drawbacks...

  17. Potential of amino acid/dipeptide monoester prodrugs of floxuridine in facilitating enhanced delivery of active drug to interior sites of tumors: a two-tier monolayer in vitro study.

    Science.gov (United States)

    Tsume, Yasuhiro; Hilfinger, John M; Amidon, Gordon L

    2011-10-01

    To evaluate the advantages of amino acid/dipeptide monoester prodrugs for cancer treatments by assessing the uptake and cytotoxic effects of floxuridine prodrugs in a secondary cancer cell monolayer following permeation across a primary cancer cell monolayer. The first Capan-2 monolayer was grown on membrane transwell inserts; the second monolayer was grown at the bottom of a plate. The permeation of floxuridine and its prodrugs across the first monolayer and the uptake and cell proliferation assay on secondary layer were sequentially determined. All floxuridine prodrugs exhibited greater permeation across the first Capan-2 monolayer than the parent drug. The correlation between uptake and growth inhibition in the second monolayer with intact prodrug permeating the first monolayer suggests that permeability and enzymatic stability are essential for sustained action of prodrugs in deeper layers of tumors. The correlation of uptake and growth inhibition were vastly superior for dipeptide prodrugs to those obtained with mono amino acid prodrugs. Although a tentative general overall correlation between intact prodrug and uptake or cytotoxic action was obtained, it appears that a mixture of floxuridine prodrugs with varying beneficial characteristics may be more effective in treating tumors.

  18. Different mathematical processing of absorption, ratio and derivative spectra for quantification of mixtures containing minor component: An application to the analysis of the recently co-formulated antidiabetic drugs; canagliflozin and metformin

    Science.gov (United States)

    Lotfy, Hayam M.; Mohamed, Dalia; Elshahed, Mona S.

    2018-01-01

    In the presented work several spectrophotometric methods were performed for the quantification of canagliflozin (CGZ) and metformin hydrochloride (MTF) simultaneously in their binary mixture. Two of these methods; response correlation (RC) and advanced balance point-spectrum subtraction (ABP-SS) were developed and introduced for the first time in this work, where the latter method (ABP-SS) was performed on both the zero order and the first derivative spectra of the drugs. Besides, two recently established methods; advanced amplitude modulation (AAM) and advanced absorbance subtraction (AAS) were also accomplished. All the proposed methods were validated in accordance to the ICH guidelines, where all methods were proved to be accurate and precise. Additionally, the linearity range, limit of detection and limit of quantification were determined and the selectivity was examined through the analysis of laboratory prepared mixtures and the combined dosage form of the drugs. The proposed methods were capable of determining the two drugs in the ratio present in the pharmaceutical formulation CGZ:MTF (1:17) without the requirement of any preliminary separation, further dilution or standard spiking. The results obtained by the proposed methods were in compliance with the reported chromatographic method when compared statistically, proving the absence of any significant difference in accuracy and precision between the proposed and reported methods.

  19. Drug Facts

    Medline Plus

    Full Text Available ... Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? ... Drug Use and Other People Drug Use and Families Drug Use and Kids Drug Use and Unborn ...

  20. Drug Facts

    Medline Plus

    Full Text Available ... Facts Search form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, ... Drugs? Effects of Drugs Drug Use and Other People Drug Use and Families Drug Use and Kids ...

  1. Drug Facts

    Medline Plus

    Full Text Available ... People Drug Use and Families Drug Use and Kids Drug Use and Unborn Children Drug Use and ... Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used ...

  2. Facilitating Knowledge Sharing

    DEFF Research Database (Denmark)

    Holdt Christensen, Peter

    knowledge sharing is to ensure that the exchange is seen as equitable for the parties involved, and by viewing the problems of knowledge sharing as motivational problems situated in different organizational settings, the paper explores how knowledge exchange can be conceptualized as going on in four...... distinct situations of exchange denominated organizational exchange yielding extrinsic rewards, organizational exchange yielding intrinsic rewards, financial exchange, and social exchange. The paper argues that each situation of exchange has distinct assumptions about individual behaviour...... and the intermediaries regulating the exchange, and facilitating knowledge sharing should therefore be viewed as a continuum of practices under the influence of opportunistic behaviour, obedience or organizational citizenship behaviour. Keywords: Knowledge sharing, motivation, organizational settings, situations...

  3. Supersaturating drug delivery systems

    DEFF Research Database (Denmark)

    Laitinen, Riikka; Löbmann, Korbinian; Grohganz, Holger

    2017-01-01

    of the bioavailability of poorly water-soluble drugs by increasing the driving force for drug absorption. However, ASDs often require a high weight percentage of carrier (usually a hydrophilic polymer) to ensure molecular mixing of the drug in the carrier and stabilization of the supersaturated state, often leading......Amorphous solid dispersions (ASDs) are probably the most common and important supersaturating drug delivery systems for the formulation of poorly water-soluble compounds. These delivery systems are able to achieve and maintain a sustained drug supersaturation which enables improvement...... strategy for poorly-soluble drugs. While the current research on co-amorphous formulations is focused on preparation and characterization of these systems, more detailed research on their supersaturation and precipitation behavior and the effect of co-formers on nucleation and crystal growth inhibition...

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

    Science.gov (United States)

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

    2008-09-24

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

  5. Mechanisms for oral absorption of poorly water-soluble compounds

    DEFF Research Database (Denmark)

    Lind, Marianne Ladegaard

    Abstract A large part of the new drug candidates discovered by the pharmaceutical industry have poor solubility in aqueous media. The preferred route of drug administration is the oral route, but for these poorly water-soluble drug candidates the oral bioavailability can be low and variable. Often......, phospholipids) and exogenous surfactants used in pharmaceutical formulations on the oral absorption of poorly water-soluble drug substances. Three different models were used for this purpose. The first model was the in vitro Caco-2 cell model. Simulated intestinal fluids which did not decrease cellular...... products are important for the solubilization of poorly water-soluble drug substances and thus absorption. The second model used was the lipoprotein secreting Caco-2 cell model, which was used to simulate intestinal lymphatic transport in vitro. Various simulated intestinal fluids were composed...

  6. Linear absorptive dielectrics

    Science.gov (United States)

    Tip, A.

    1998-06-01

    Starting from Maxwell's equations for a linear, nonconducting, absorptive, and dispersive medium, characterized by the constitutive equations D(x,t)=ɛ1(x)E(x,t)+∫t-∞dsχ(x,t-s)E(x,s) and H(x,t)=B(x,t), a unitary time evolution and canonical formalism is obtained. Given the complex, coordinate, and frequency-dependent, electric permeability ɛ(x,ω), no further assumptions are made. The procedure leads to a proper definition of band gaps in the periodic case and a new continuity equation for energy flow. An S-matrix formalism for scattering from lossy objects is presented in full detail. A quantized version of the formalism is derived and applied to the generation of Čerenkov and transition radiation as well as atomic decay. The last case suggests a useful generalization of the density of states to the absorptive situation.

  7. Gamma absorption meter

    International Nuclear Information System (INIS)

    Dincklage, R.D. von.

    1984-01-01

    The absorption meter consists of a radiation source, a trough for the absorbing liquid and a detector. It is characterized by the fact that there is a foil between the detector and the trough, made of a material whose binding energy of the K electrons is a little greater than the energy of the photons emitted by the radiation source. The source of radiation and foil are replaceable. (orig./HP) [de

  8. Total Absorption Spectroscopy

    International Nuclear Information System (INIS)

    Rubio, B.; Gelletly, W.

    2007-01-01

    The problem of determining the distribution of beta decay strength (B(GT)) as a function of excitation energy in the daughter nucleus is discussed. Total Absorption Spectroscopy is shown to provide a way of determining the B(GT) precisely. A brief history of such measurements and a discussion of the advantages and disadvantages of this technique, is followed by examples of two recent studies using the technique. (authors)

  9. Expert and novice facilitated modelling

    DEFF Research Database (Denmark)

    Tavella, Elena; Papadopoulos, Thanos

    2015-01-01

    , and empirically supports the claim that facilitation skills can be taught to participants to enable them to self-facilitate workshops. Differences were also found, which led to the introduction of a new dimension—‘internal versus external’ facilitation. The implications of our findings for effective training...

  10. Drug metabolism and ageing.

    Science.gov (United States)

    Wynne, Hilary

    2005-06-01

    Older people are major consumers of drugs and because of this, as well as co-morbidity and age-related changes in pharmacokinetics and pharmacodynamics, are at risk of associated adverse drug reactions. While age does not alter drug absorption in a clinically significant way, and age-related changes in volume of drug distribution and protein binding are not of concern in chronic therapy, reduction in hepatic drug clearance is clinically important. Liver blood flow falls by about 35% between young adulthood and old age, and liver size by about 24-35% over the same period. First-pass metabolism of oral drugs avidly cleared by the liver and clearance of capacity-limited hepatically metabolized drugs fall in parallel with the fall in liver size, and clearance of drugs with a high hepatic extraction ratio falls in parallel with the fall in hepatic blood flow. In normal ageing, in general, activity of the cytochrome P450 enzymes is preserved, although a decline in frail older people has been noted, as well as in association with liver disease, cancer, trauma, sepsis, critical illness and renal failure. As the contribution of age, co-morbidity and concurrent drug therapy to altered drug clearance is impossible to predict in an individual older patient, it is wise to start any drug at a low dose and increase this slowly, monitoring carefully for beneficial and adverse effects.

  11. Slow-light enhancement of Beer-Lambert-Bouguer absorption

    OpenAIRE

    Mortensen, Niels Asger; Xiao, Sanshui

    2007-01-01

    We theoretically show how slow light in an optofluidic environment facilitates enhanced light-matter interactions, by orders of magnitude. The proposed concept provides strong opportunities for improving existing miniaturized chemical absorbance cells for Beer-Lambert-Bouguer absorption measurements widely employed in analytical chemistry.

  12. Facilitating post traumatic growth

    Directory of Open Access Journals (Sweden)

    Cox Helen

    2004-07-01

    Full Text Available Abstract Background Whilst negative responses to traumatic injury have been well documented in the literature, there is a small but growing body of work that identifies posttraumatic growth as a salient feature of this experience. We contribute to this discourse by reporting on the experiences of 13 individuals who were traumatically injured, had undergone extensive rehabilitation and were discharged from formal care. All participants were injured through involvement in a motor vehicle accident, with the exception of one, who was injured through falling off the roof of a house. Methods In this qualitative study, we used an audio-taped in-depth interview with each participant as the means of data collection. Interviews were transcribed verbatim and analysed thematically to determine the participants' unique perspectives on the experience of recovery from traumatic injury. In reporting the findings, all participants' were given a pseudonym to assure their anonymity. Results Most participants indicated that their involvement in a traumatic occurrence was a springboard for growth that enabled them to develop new perspectives on life and living. Conclusion There are a number of contributions that health providers may make to the recovery of individuals who have been traumatically injured to assist them to develop new views of vulnerability and strength, make changes in relationships, and facilitate philosophical, physical and spiritual growth.

  13. SSRI Facilitated Crack Dancing

    Directory of Open Access Journals (Sweden)

    Ravi Doobay

    2017-01-01

    Full Text Available Choreoathetoid movement secondary to cocaine use is a well-documented phenomenon better known as “crack dancing.” It consists of uncontrolled writhing movements secondary to excess dopamine from cocaine use. We present a 32-year-old male who had been using cocaine for many years and was recently started on paroxetine, a selective serotonin reuptake inhibitor (SSRI for worsening depression four weeks before presentation. He had been doing cocaine every 2 weeks for the last three years and had never “crack danced” before this episode. The authors have conducted a thorough literature review and cited studies that suggest “crack dancing” is associated with excess dopamine. There has never been a documented case report of an SSRI being linked with “crack dancing.” The authors propose that the excess dopaminergic effect of the SSRI lowered the dopamine threshold for “crack dancing.” There is a communication with the Raphe Nucleus and the Substantia Nigra, which explains how the SSRI increases dopamine levels. This is the first documented case of an SSRI facilitating the “crack dance.”

  14. Skin absorption through atopic dermatitis skin

    DEFF Research Database (Denmark)

    Halling-Overgaard, A-S; Kezic, S; Jakasa, I

    2017-01-01

    Patients with atopic dermatitis have skin barrier impairment in both lesional and non-lesional skin. They are typically exposed to emollients daily and topical anti-inflammatory medicaments intermittently, hereby increasing the risk of developing contact allergy and systemic exposed to chemicals...... ingredients found in these topical preparations. We systematically searched for studies that investigated skin absorption of various penetrants, including medicaments, in atopic dermatitis patients, but also animals with experimentally induced dermatitis. We identified 40 articles, i.e. 11 human studies...... examining model penetrants, 26 human studies examining atopic dermatitis drugs and 3 animal studies. We conclude that atopic dermatitis patients have nearly two-fold increased skin absorption when compared to healthy controls. There is a need for well-designed epidemiological and dermato...

  15. Drugs and the Brain: An Introduction to Neuropharmacology. Pamphlet Series.

    Science.gov (United States)

    Brick, John

    The thousands of different drugs on the market can be separated into two categories: drugs that affect behavior, called psychoactive drugs, and drugs that do not affect behavior. Drugs get into the body by mouth, inhalation into the lungs, by injection into a vein, muscle or under the skin, and by absorption through mucous membranes. Regardless of…

  16. Optical absorption in dendrimers

    International Nuclear Information System (INIS)

    Supritz, C.; Engelmann, A.; Reineker, P.

    2004-01-01

    Dendrimers are highly branched molecules, which are expected to be useful, for example, as efficient artificial light harvesting systems in nano-technological applications. There are two different classes of dendrimers: compact dendrimers with constant distance between neighboring branching points throughout the macromolecule and extended dendrimers, where this distance increases from the system periphery to the center. We investigate the linear absorption spectra of these dendrimer types using the Frenkel exciton concept. The electron-phonon interaction is taken into account by introducing a heat bath that interacts with the exciton in a stochastic manner

  17. Rapidly variable relatvistic absorption

    Science.gov (United States)

    Parker, M.; Pinto, C.; Fabian, A.; Lohfink, A.; Buisson, D.; Alston, W.; Jiang, J.

    2017-10-01

    I will present results from the 1.5Ms XMM-Newton observing campaign on the most X-ray variable AGN, IRAS 13224-3809. We find a series of nine absorption lines with a velocity of 0.24c from an ultra-fast outflow. For the first time, we are able to see extremely rapid variability of the UFO features, and can link this to the X-ray variability from the inner accretion disk. We find a clear flux dependence of the outflow features, suggesting that the wind is ionized by increasing X-ray emission.

  18. Impact of Pharmacist Facilitated Discharge Medication Reconciliation

    Directory of Open Access Journals (Sweden)

    Todd M. Super

    2014-07-01

    Full Text Available Preventable adverse drug events occur frequently at transitions in care and are a problem for many patients following hospital discharge. Many of these problems can be attributed to poor medication reconciliation. The purpose of this study was to assess the impact that direct pharmacist involvement in the discharge medication reconciliation process had on medication discrepancies, patient outcomes, and satisfaction. A cohort study of 70 patients was designed to assess the impact of pharmacist facilitated discharge medication reconciliation at a 204-bed community hospital in Battle Creek, Michigan, USA. Discharge summaries were analyzed to compare patients who received standard discharge without pharmacist involvement to those having pharmacist involvement. The total number of discrepancies in the group without pharmacist involvement was significantly higher than that of the pharmacist facilitated group.

  19. Pharmacokinetic aspects of the anti-epileptic drug substance vigabatrin

    DEFF Research Database (Denmark)

    Nøhr, Martha Kampp; Frølund, Sidsel; Holm, René

    2014-01-01

    are discussed in detail. Special focus is on the contribution of the proton-coupled amino acid transporter 1 (PAT1) for intestinal vigabatrin absorption. Furthermore, the review gives an overview of the pharmacokinetic parameters of vigabatrin across different species and drug-food and drug-drug interactions......Drug transporters in various tissues, such as intestine, kidney, liver and brain, are recognized as important mediators of absorption, distribution, metabolism and excretion of drug substances. This review gives a current status on the transporter(s) mediating the absorption, distribution......, metabolism and excretion properties of the anti-epileptic drug substance vigabatrin. For orally administered drugs, like vigabatrin, the absorption from the intestine is a prerequisite for the bioavailability. Therefore, transporter(s) involved in the intestinal absorption of vigabatrin in vitro and in vivo...

  20. Geospatial Absorption and Regional Effects

    Directory of Open Access Journals (Sweden)

    IOAN MAC

    2009-01-01

    Full Text Available The geospatial absorptions are characterized by a specific complexity both in content and in their phenomenological and spatial manifestation fields. Such processes are differentiated according to their specificity to pre-absorption, absorption or post-absorption. The mechanisms that contribute to absorption are extremely numerous: aggregation, extension, diffusion, substitution, resistivity (resilience, stratification, borrowings, etc. Between these mechanisms frequent relations are established determining an amplification of the process and of its regional effects. The installation of the geographic osmosis phenomenon in a given territory (a place for example leads to a homogenization of the geospatial state and to the installation of the regional homogeneity.

  1. Drug Facts

    Medline Plus

    Full Text Available ... Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used Drugs in the Past Drug Use ... Videos Information About Drugs Alcohol ...

  2. Drug Allergy

    Science.gov (United States)

    ... Loss of consciousness Other conditions resulting from drug allergy Less common drug allergy reactions occur days or ... you take the drug. Drugs commonly linked to allergies Although any drug can cause an allergic reaction, ...

  3. Facilitating functional annotation of chicken microarray data

    Directory of Open Access Journals (Sweden)

    Gresham Cathy R

    2009-10-01

    Full Text Available Abstract Background Modeling results from chicken microarray studies is challenging for researchers due to little functional annotation associated with these arrays. The Affymetrix GenChip chicken genome array, one of the biggest arrays that serve as a key research tool for the study of chicken functional genomics, is among the few arrays that link gene products to Gene Ontology (GO. However the GO annotation data presented by Affymetrix is incomplete, for example, they do not show references linked to manually annotated functions. In addition, there is no tool that facilitates microarray researchers to directly retrieve functional annotations for their datasets from the annotated arrays. This costs researchers amount of time in searching multiple GO databases for functional information. Results We have improved the breadth of functional annotations of the gene products associated with probesets on the Affymetrix chicken genome array by 45% and the quality of annotation by 14%. We have also identified the most significant diseases and disorders, different types of genes, and known drug targets represented on Affymetrix chicken genome array. To facilitate functional annotation of other arrays and microarray experimental datasets we developed an Array GO Mapper (AGOM tool to help researchers to quickly retrieve corresponding functional information for their dataset. Conclusion Results from this study will directly facilitate annotation of other chicken arrays and microarray experimental datasets. Researchers will be able to quickly model their microarray dataset into more reliable biological functional information by using AGOM tool. The disease, disorders, gene types and drug targets revealed in the study will allow researchers to learn more about how genes function in complex biological systems and may lead to new drug discovery and development of therapies. The GO annotation data generated will be available for public use via AgBase website and

  4. Chitosan Based Self-Assembled Nanoparticles in Drug Delivery

    Directory of Open Access Journals (Sweden)

    Javier Pérez Quiñones

    2018-02-01

    Full Text Available Chitosan is a cationic polysaccharide that is usually obtained by alkaline deacetylation of chitin poly(N-acetylglucosamine. It is biocompatible, biodegradable, mucoadhesive, and non-toxic. These excellent biological properties make chitosan a good candidate for a platform in developing drug delivery systems having improved biodistribution, increased specificity and sensitivity, and reduced pharmacological toxicity. In particular, chitosan nanoparticles are found to be appropriate for non-invasive routes of drug administration: oral, nasal, pulmonary and ocular routes. These applications are facilitated by the absorption-enhancing effect of chitosan. Many procedures for obtaining chitosan nanoparticles have been proposed. Particularly, the introduction of hydrophobic moieties into chitosan molecules by grafting to generate a hydrophobic-hydrophilic balance promoting self-assembly is a current and appealing approach. The grafting agent can be a hydrophobic moiety forming micelles that can entrap lipophilic drugs or it can be the drug itself. Another suitable way to generate self-assembled chitosan nanoparticles is through the formation of polyelectrolyte complexes with polyanions. This paper reviews the main approaches for preparing chitosan nanoparticles by self-assembly through both procedures, and illustrates the state of the art of their application in drug delivery.

  5. Drug-mineral interactions

    International Nuclear Information System (INIS)

    Kramer, L.

    1986-01-01

    The effect of drugs such as glucocorticoids and thyroid extract on calcium metabolism is unknown. However, several other medications affect the excretion and intestinal absorption of calcium. A controlled study was carried out to investigate these aspects. Urinary calcium was determined for 3 months during the long-term intake of the antituberculous drug isoniazid (INH) and of the antibiotic tetracycline. The effect of the diuretics furosemide and hydrochlorothiazide, of several aluminum-containing antacids, of thyroid extract and of corticosteroids was also studied. Metabolic balances of calcium, phosphorus, magnesium and zinc were determined, as well as the intestinal absorption of calcium using Ca 47. Plasma levels, urinary and fecal excretions of Ca 47 were determined. All drugs tested increased urinary calcium except for the diuretic hydrochlorothiazide. Regarding the effect of corticosteroids: the intestinal absorption of calcium was unchanged after the short-term use and was very high after long-term use. The studies have shown that several commonly used drugs induce an increase in urinary calcium excretion which may contribute to calcium loss, if this increase persists for prolonged periods of time. Urinary excretions of phosphorus, magnesium and zinc increased in some of the studies

  6. Atomic absorption spectrometry

    International Nuclear Information System (INIS)

    Haswell, S.J.

    1991-01-01

    Atomic absorption spectroscopy is now well established and widely used technique for the determination of trace and major elements in a wide range analyte types. There have been many advances in the atomic spectroscopy over the last decade and for this reason and to meet the demand, it was felt that there was a need for an updated book. Whilst interest in instrumental design has tended to dominate the minds of the spectrocopist, the analyst concerned with obtaining reliable and representative data, in diverse areas of application, has been diligently modifying and developing sample treatment and instrumental introduction techniques. Such methodology is de fundamental part of analysis and form the basis of the fourteen application chapters of this book. The text focuses in the main on AAS; however, the sample handling techniques described are in many cases equally applicable to ICP-OES and ICP-MS analysis. (author). refs.; figs.; tabs

  7. Atomic absorption spectrophotometer

    International Nuclear Information System (INIS)

    Stockdale, T. J.

    1985-01-01

    In atomic absorption spectrophotometer, a reference path may be provided for radiation which excludes the flame. This radiation provides a signal from a detector which varies only with the instrumental drift produced by variations in the radiation source brightness and by variations in detector gain. The signal can be used to compensate for drift in other signals received through a sample path including the flame. In the present invention, radiation passes through the sample path continuously during measurement, and only through the reference path between sample measurements. Movable mirrors shift the radiation between the paths upon externally applied commands. Conveniently, the reference path measurement is made while the flame is stabilized during the change between samples. The reference path measurements are stored and used to correct for drift

  8. Analyzing Water's Optical Absorption

    Science.gov (United States)

    2002-01-01

    A cooperative agreement between World Precision Instruments (WPI), Inc., and Stennis Space Center has led the UltraPath(TM) device, which provides a more efficient method for analyzing the optical absorption of water samples at sea. UltraPath is a unique, high-performance absorbance spectrophotometer with user-selectable light path lengths. It is an ideal tool for any study requiring precise and highly sensitive spectroscopic determination of analytes, either in the laboratory or the field. As a low-cost, rugged, and portable system capable of high- sensitivity measurements in widely divergent waters, UltraPath will help scientists examine the role that coastal ocean environments play in the global carbon cycle. UltraPath(TM) is a trademark of World Precision Instruments, Inc. LWCC(TM) is a trademark of World Precision Instruments, Inc.

  9. The role of social capital in the creation of organisational absorptive capacity

    DEFF Research Database (Denmark)

    Bergenholtz, Carsten

    2010-01-01

    Based on a double case-study, this paper discusses the role of social capital in the creation of organisational absorptive capacity. Bridging social capital makes it possible to acquire new knowledge whereas bonding social capital assists the exploitation of that knowledge. In addition, this study...... presents a concept of creative social capital to facilitate the transition from assimilation to transformation. Two action research cases present the generation of social interaction mechanisms that facilitate the move from potential absorptive capacity to realised absorptive capacity. In these cases...... the creative social capital is being concretised as a) group-based identity, and b) willingness to form a mutual goal....

  10. Preeclampsia – Will Orphan Drug Status Facilitate Innovative Biological Therapies?

    Science.gov (United States)

    Hahn, Sinuhe

    2015-01-01

    It is generally accepted that the development of novel therapies to treat pregnancy-related disorders, such as preeclampsia, is hampered by the paucity of research funding. Hence, it is with great interest to become aware of at least three novel therapeutic approaches for the treatment of this disorder: exploiting either the anticoagulant activity of antithrombin, the free radical scavenging activity of alpha-1-microglobulin, or the regenerative capacity of placenta-derived mesenchymal stem cells. As these projects are being carried out by small biotech enterprises, the question arises of how they are able to fund such undertakings. A novel strategy adopted by two of these companies is that they successfully petitioned US and EU agencies in order that preeclampsia is accepted in the register of rare or orphan diseases. This provides a number of benefits including market exclusivity, assistance with clinical trials, and dedicated funding schemes. Other strategies to supplement meager research funds, especially to test novel approaches, could be crowdfunding, a venture that relies on intimate interaction with advocacy groups. In other words, preeclampsia meets Facebook. Perhaps similar strategies can be adopted to examine novel therapies targeting either the imbalance in pro- or anti-angiogenic growth factors, complement activation, reduced levels of placenta protein 13, or excessive neutrophil activation evident in preeclampsia. PMID:25767802

  11. Preeclampsia - will orphan drug status facilitate innovative biological therapies?

    Science.gov (United States)

    Hahn, Sinuhe

    2015-01-01

    It is generally accepted that the development of novel therapies to treat pregnancy-related disorders, such as preeclampsia, is hampered by the paucity of research funding. Hence, it is with great interest to become aware of at least three novel therapeutic approaches for the treatment of this disorder: exploiting either the anticoagulant activity of antithrombin, the free radical scavenging activity of alpha-1-microglobulin, or the regenerative capacity of placenta-derived mesenchymal stem cells. As these projects are being carried out by small biotech enterprises, the question arises of how they are able to fund such undertakings. A novel strategy adopted by two of these companies is that they successfully petitioned US and EU agencies in order that preeclampsia is accepted in the register of rare or orphan diseases. This provides a number of benefits including market exclusivity, assistance with clinical trials, and dedicated funding schemes. Other strategies to supplement meager research funds, especially to test novel approaches, could be crowdfunding, a venture that relies on intimate interaction with advocacy groups. In other words, preeclampsia meets Facebook. Perhaps similar strategies can be adopted to examine novel therapies targeting either the imbalance in pro- or anti-angiogenic growth factors, complement activation, reduced levels of placenta protein 13, or excessive neutrophil activation evident in preeclampsia.

  12. Preeclampsia – will Orphan Drug Status facilitate innovative biological therapies?

    Directory of Open Access Journals (Sweden)

    Sinuhe eHahn

    2015-02-01

    Full Text Available It is generally accepted that development of novel therapies to treat pregnancy-relates disorders, such as preeclampsia, is hampered to the paucity of research funding. Hence, it is with great interest to become aware of at least three novel therapeutic approaches for the treatment of this disorder, exploiting either the anticoagulant activity of antithrombin, the free radical scavenging activity of alpha-1-microglobulin, or the regenerative capacity of placenta-derived mesenchymal stem cells. As these projects are being carried out by small biotech enterprises, the question arises of how they are able to fund such undertakings. A novel strategy adopted by two of these companies is that they successfully petitioned US and EU agencies in order that preeclampsia be accepted in the register of rare or orphan diseases. This provides a number of benefits including market exclusivity, assistance with clinical trials and dedicated funding schemes. Other strategies to supplement meager research funds, especially to test novel approaches, could be crowdfunding, a venture which relies on intimate interaction with advocacy groups. In other words, preeclampsia meets Facebook. Perhaps similar strategies can be adopted to examine novel therapies targeting either the imbalance in angiogenic growth factors, complement activation, reduced levels of placenta protein 13 or excessive neutrophil activation evident in preeclampsia.

  13. Atomic absorption spectrophotometry in perspective

    International Nuclear Information System (INIS)

    Soffiantini, V.

    1981-01-01

    Atomic absorption spectrophotometry is essentially an analytical technique used for quantitative trace metal analysis in a variety of materials. The speed and specificity of the technique is its greatest advantage over other analytical techniques. What atomic absorption spectrophotometry can and cannot do and its advantages and disadvantages are discussed, a summary of operating instructions are given, as well as a summary of analytical interferences. The applications of atomic absorption spectrophotometry are also shortly discussed

  14. Nonlinear effects in collective absorption

    International Nuclear Information System (INIS)

    Uenoyama, Takeshi; Mima, Kunioki; Watanabe, Tsuguhiro.

    1981-01-01

    The collective absorption of high intensity laser radiation is analyzed numerically. Density profile modification due to the ponderomotive force associating laser radiation and the excited electron plasma waves is self-consistently taken into account, and the intensity dependences of the absorption efficiency are obtained. In the high intensity regime, the absorption efficiency is found to be strongly enhanced in the plasma without flow, but reduced with supersonic flow. (author)

  15. X-ray Absorption Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Yano, Junko; Yachandra, Vittal K.

    2009-07-09

    This review gives a brief description of the theory and application of X-ray absorption spectroscopy, both X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS), especially, pertaining to photosynthesis. The advantages and limitations of the methods are discussed. Recent advances in extended EXAFS and polarized EXAFS using oriented membranes and single crystals are explained. Developments in theory in understanding the XANES spectra are described. The application of X-ray absorption spectroscopy to the study of the Mn4Ca cluster in Photosystem II is presented.

  16. Use of a standard meal to study iron absorption in humans

    International Nuclear Information System (INIS)

    Reddy, M.B.; Cook, J.D.

    1994-01-01

    Iron absorption varies widely between subjects and groups of subjects because of differences in iron status which markedly influence iron assimilation from the gastrointestinal tract. A small dose of isotopically labelled inorganic iron termed the reference dose (3 mg iron as FeSO 4 ) has been used extensively during the past two decades to standardize food iron absorption in human subjects and thereby eliminate the effect of differences in iron status. Recent studies from this laboratory have shown that because of the high variability of absorption from the reference dose, nonheme iron absorption from a standardized meal provides a more reliable means of standardizing absorption from regional diets. We therefore performed initial studies with a rice based meal but we found a relatively high variation in absorption from 2.0 to 4.7% that presumably reflects differences in the phytate content of rice fours. We then undertook the evaluation of meals prepared with farina, a wheat product that is available in most regions of the world. In six different studies from a farina based meal, iron absorption ranged from 3.4 to 6.5%. Nonheme iron absorption from the farina meal when evaluated in separate laboratories extensively engaged in human studies of iron absorption, ranged from 5.1 to 10.8% but when related to the FeSO 4 dose, a more consistent ratio between 0.21 to 0.26 was observed with the exception of one laboratory where a very low absorption of 1.1.% was observed. Percentage absorption from the farina based meal decreased when the iron content of the meal was increased and showed the expected facilitation of absorption when increasing amounts of ascorbic acid were added. By reducing variability and measuring iron absorption from food rather than inorganic iron, we believe that the use of this standard meal will facilitate comparison of iron absorption data obtained in laboratories throughout the world. 4 refs, 2 tabs

  17. Glucose Absorption by the Bacillary Band of Trichuris muris.

    Directory of Open Access Journals (Sweden)

    Tina V A Hansen

    2016-09-01

    Full Text Available A common characteristic of Trichuris spp. infections in humans and animals is the variable but low efficacy of single-dose benzimidazoles currently used in mass drug administration programmes against human trichuriasis. The bacillary band, a specialised morphological structure of Trichuris spp., as well as the unique partly intracellular habitat of adult Trichuris spp. may affect drug absorption and perhaps contribute to the low drug accumulation in the worm. However, the exact function of the bacillary band is still unknown.We studied the dependency of adult Trichuris muris on glucose and/or amino acids for survival in vitro and the absorptive function of the bacillary band. The viability of the worms was evaluated using a motility scale from 0 to 3, and the colorimetric assay Alamar Blue was utilised to measure the metabolic activity. The absorptive function of the bacillary band in living worms was explored using a fluorescent glucose analogue (6-NBDG and confocal microscopy. To study the absorptive function of the bacillary band in relation to 6-NBDG, the oral uptake was minimised or excluded by sealing the oral cavity with glue and agarose.Glucose had a positive effect on both the motility (p < 0.001 and metabolic activity (p < 0.001 of T. muris in vitro, whereas this was not the case for amino acids. The 6-NBDG was observed in the pores of the bacillary band and within the stichocytes of the living worms, independent of oral sealing.Trichuris muris is dependent on glucose for viability in vitro, and the bacillary band has an absorptive function in relation to 6-NBDG, which accumulates within the stichocytes. The absorptive function of the bacillary band calls for an exploration of its possible role in the uptake of anthelmintics, and as a potential anthelmintic target relevant for future drug development.

  18. Drug Safety

    Science.gov (United States)

    ... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

  19. Drug Abuse

    Science.gov (United States)

    ... Cocaine Heroin Inhalants Marijuana Prescription drugs, including opioids Drug abuse also plays a role in many major social problems, such as drugged driving, violence, stress, and child abuse. Drug abuse can lead to ...

  20. Drug Facts

    Medline Plus

    Full Text Available ... Use and Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug ...

  1. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use and Kids Drug Use and Unborn Children Drug Use and Your Health Other Effects on ... Someone Find Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids ...

  2. Club Drugs

    Science.gov (United States)

    ... uses. Other uses of these drugs are abuse. Club drugs are also sometimes used as "date rape" drugs, to make someone unable to say no to or fight back against sexual assault. Abusing these drugs can ...

  3. Galactic absorption line coronae

    International Nuclear Information System (INIS)

    Bregman, J.N.

    1981-01-01

    We have investigated whether gaseous coronae around galaxies rise to the absorption systems seen in quasar spectra. In our model, gas originally located in the disk is heated to the million degree range and rises to surround the galaxy; the gas remains bound to the galaxy. Optically thin radiative cooling drives a thermal instability in the hot gas which causes cool clouds (T 4 K) to condense out of the corona. These clouds, which follow ballistic trajectories back to the disk, are the absorption sites. A two-dimensional hydrodynamic code with radiative cooling was used to study the dynamics and thermodynamics of the corona as well as the position rate at which clouds form. Coupled to the code is a galaxy with two mass components, a disk (approx.10 11 M/sub sun/) and a dark halo (approx.10 12 M/sub sun/). In a model where the temperature at the base of the corona (in the disk) is 3 x 10 6 K, absorbing gas of column density NL> or approx. =10 18 cm 2 extends radially to 100 kpc (face-on orientation) and vertically to 60 Kpc (edge-on orientation). The total mass of gas required here (coronal plus cloud gas) is 1.4 x 10 10 M/sub sun/, while the minimum supernova heating rate is one supernova per 27 years. In two other models (base coronal temperatures of 0.50 x 10 6 K and 1 x 10 6 K), coronal gas rises from an extended gaseous disk (in the previous model, the gas comes from a typical gaseous disk approximately 15 kpc in extent). Here, column densities of 10 19 cm -2 out to a radius of 70 kpc (face-on orientation) are achieved with a total gas mass of 1.7 x 10 9 M/sub direct-product/ and 2.0 x 10 9 M/sub sun/ and minimum heating rates of approximately one supernova per 170 years and one supernova per 60 years

  4. Cell-patterned glass spray for direct drug assay using mass spectrometry

    International Nuclear Information System (INIS)

    Wu, Jing; Wang, Shiqi; Chen, Qiushui; Jiang, Hao; Liang, Shuping; Lin, Jin-Ming

    2015-01-01

    In this work, the establishment of a glass spray mass spectrometry (GS-MS) platform for direct cell-based drug assay was described. Cell co-culture, drug-induced cell apoptosis, proliferation analysis and intracellular drug absorption measurement were performed simultaneously on this specifically designed platform. Two groups of co-cultured cells (NIH-3T3/HepG2 and HepG2/MCF-7) were cultivated and they showed high viability within 3 days. The biocompatibility of the platform facilitated the subsequent bioassays, in which, cyclophosphamide (CPA) and genistein were used as the model drugs. The distinctions of cell apoptosis and proliferation between the mono-cultured and co-cultured cells were clearly observed and well explained by in situ GS-MS measurements. A satisfactory linearity of the calibration curve between the relative MS intensity and CPA concentrations was obtained using stable isotope labeling method (y = 0.16545 + 0.0985x, R"2 = 0.9937). The variations in the quantity of absorbed drug were detected and the results were consistent with the concentration-dependence of cell apoptosis. All the results demonstrated that direct cell-based drug assay could be performed on the stable isotope labeling assisted GS-MS platform in a facile and quantitative manner. - Highlights: • A versatile glass spray mass spectrometry (GS-MS) platform for direct cell-based drug assay was developed in this paper. • It has characteristics of the atmospheric pressure ionization method. • It is multifunctional for cell co-culture, bioassays, qualitative and quantitative intracellular drug absorption measurement. • GS-MS has the potential to increase the use of mass spectrometry in biological analysis.

  5. Nasal Inserts for Drug Delivery: An Overview

    African Journals Online (AJOL)

    In this review, the benefits, limitations and absorption mechanisms of the nasal route, as well ... molecules including peptide and proteins for ... (Mw) drugs, rapid and fast onset of action due to ... while the former act by disrupting the nasal.

  6. Polymeric nanoparticles developed by vitamin E-modified aliphatic polycarbonate polymer to promote oral absorption of oleanolic acid

    Directory of Open Access Journals (Sweden)

    Wenjuan Zhang

    2017-11-01

    Full Text Available Oleanolic acid (OA exhibited good pharmacological activities in the clinical treatment of hypoglycemia, immune regulation, acute jaundice and chronic toxic hepatitis. However, the oral delivery of OA is greatly limited by its inferior water solubility and poor intestinal mucosa permeability. Herein, we developed a novel polymeric nanoparticle (NP delivery system based on vitamin E modified aliphatic polycarbonate (mPEG-PCC-VE to facilitate oral absorption of OA. OA encapsulated mPEG-PCC-VE NPs (OA/mPEG-PCC-VE NPs showed uniform particle size of about 170 nm with high drug loading capability (8.9%. Furthermore, the polymeric mPEG-PCC-VE NPs, with good colloidal stability and pH-sensitive drug release characteristics, significantly enhanced the in vitro dissolution of OA in the alkaline medium. The in situ single pass intestinal perfusion (SPIP studies performed on rats demonstrated that the OA/mPEG-PCC-VE NPs showed significantly improved permeability in the whole intestinal tract when compared to OA solution, especially for duodenum and colon. As a result, the in vivo pharmacokinetics study indicated that the bioavailability of OA/mPEG-PCC-VE NPs showed 1.5-fold higher than commercially available OA tablets. These results suggest that mPEG-PCC-VE NPs are a promising platform to facilitate the oral delivery of OA.

  7. Wave energy absorption by ducks

    OpenAIRE

    Kurniawan, Adi

    2017-01-01

    We study the absorption of wave energy by a single and multiple cam-shaped bodies referred to as ducks. Numerical models are developed under the assumptions of linear theory. We consider wave absorption by a single duck as well as by two lines of ducks meeting at an angle.

  8. Wave energy absorption by ducks

    DEFF Research Database (Denmark)

    Kurniawan, Adi

    2018-01-01

    We study the absorption of wave energy by a single and multiple cam-shaped bodies referred to as ducks. Numerical models are developed under the assumptions of linear theory. We consider wave absorption by a single duck as well as by two lines of ducks meeting at an angle....

  9. Atomic absorption instrument functional description

    International Nuclear Information System (INIS)

    Bystroff, R.I.; Boyle, W.G. Jr.; Barton, G.W. Jr.

    1976-01-01

    This report describes a proposed system for automating atomic absorption analysis. The system consists of two atomic absorption instruments and an automatic sampler that can be attached to either instrument. A computer program controls the sampling and gathers data. The program then uses the data to perform bookkeeping, data processing, and report writing

  10. Sublinear absorption in OCS gas

    International Nuclear Information System (INIS)

    Bogani, F.; Querzoli, R.; Ernst, K.

    1988-01-01

    Sublinear absorption in OCS gas has been experimentally studied in detail by means of an optoacustic technique and transmission measurements. The best fit of the results is obtained by a phenomenological model, that considers the process as the sum of one-and two-photon absorptions

  11. Optical absorption of irradiated carbohydrates

    International Nuclear Information System (INIS)

    Supe, A.A.; Tiliks, Yu.E.

    1994-01-01

    The optical absorption spectra of γ-irradiated carbohydrates (glucose, lactose, sucrose, maltose, and starch) and their aqueous solutions were studied. The comparison of the data obtained with the determination of the concentrations of molecular and radical products of radiolysis allows the absorption bands with maxima at 250 and 310 nm to be assigned to the radicals trapped in the irradiated carbohydrates

  12. Water absorption in brick masonry

    NARCIS (Netherlands)

    Brocken, H.J.P.; Smolders, H.R.

    1996-01-01

    The water absorption in brick, mortar that was cured separately, and masonry samples was studied using NMR. Models of the moisture transport are usually formulated on the basis of a diffusion equation. In the case of water absorption in separate brick and mortar samples, the moisture diffusivity in

  13. Subgap absorption in conjugated polymers

    Energy Technology Data Exchange (ETDEWEB)

    Sinclair, M.; Seager, C.H. (Sandia National Labs., Albuquerque, NM (USA)); McBranch, D.; Heeger, A.J. (California Univ., Santa Barbara, CA (USA)); Baker, G.L. (Bell Communications Research, Inc., Red Bank, NJ (USA))

    1991-01-01

    Along with X{sup (3)}, the magnitude of the optical absorption in the transparent window below the principal absorption edge is an important parameter which will ultimately determine the utility of conjugated polymers in active integrated optical devices. With an absorptance sensitivity of < 10{sup {minus}5}, Photothermal Deflection Spectroscopy (PDS) is ideal for determining the absorption coefficients of thin films of transparent'' materials. We have used PDS to measure the optical absorption spectra of the conjugated polymers poly(1,4-phenylene-vinylene) (and derivitives) and polydiacetylene-4BCMU in the spectral region from 0.55 eV to 3 eV. Our spectra show that the shape of the absorption edge varies considerably from polymer to polymer, with polydiacetylene-4BCMU having the steepest absorption edge. The minimum absorption coefficients measured varied somewhat with sample age and quality, but were typically in the range 1 cm{sup {minus}1} to 10 cm{sup {minus}1}. In the region below 1 eV, overtones of C-H stretching modes were observed, indicating that further improvements in transparency in this spectral region might be achieved via deuteration of fluorination. 11 refs., 4 figs.

  14. Multifunctional hybrids for electromagnetic absorption

    International Nuclear Information System (INIS)

    Huynen, I.; Quievy, N.; Bailly, C.; Bollen, P.; Detrembleur, C.; Eggermont, S.; Molenberg, I.; Thomassin, J.M.; Urbanczyk, L.

    2011-01-01

    Highlights: → EM absorption requires low dielectric constant and ∼1 S/m electrical conductivity. → New hybrids were processed with CNT-filled polymer foam inserted in Al honeycomb. → The EM absorption in the GHz range is superior to any known material. → A closed form model is used to guide the design of the hybrid. → The architectured material is light with potential for thermal management. - Abstract: Electromagnetic (EM) interferences are ubiquitous in modern technologies and impact on the reliability of electronic devices and on living cells. Shielding by EM absorption, which is preferable over reflection in certain instances, requires combining a low dielectric constant with high electrical conductivity, which are antagonist properties in the world of materials. A novel class of hybrid materials for EM absorption in the gigahertz range has been developed based on a hierarchical architecture involving a metallic honeycomb filled with a carbon nanotube-reinforced polymer foam. The waveguide characteristics of the honeycomb combined with the performance of the foam lead to unexpectedly large EM power absorption over a wide frequency range, superior to any known material. The peak absorption frequency can be tuned by varying the shape of the honeycomb unit cell. A closed form model of the EM reflection and absorption provides a tool for the optimization of the hybrid. This designed material sets the stage for a new class of sandwich panels combining high EM absorption with mass efficiency, stiffness and thermal management.

  15. Assessment of absorption of four lignan constituents of JingNing ...

    African Journals Online (AJOL)

    Purpose: To study small intestinal absorption of schisadrol A, schisandrol B, schizandrin A and schisandrin B in JingNing particles using in situ single-pass intestinal perfusion (SPIP). Methods: Absorption rate constant (Ka) and apparent permeability (Papp) of the drugs at different concentrations in various parts of rat small ...

  16. Near-infrared free carrier absorption in heavily doped silicon

    International Nuclear Information System (INIS)

    Baker-Finch, Simeon C.; McIntosh, Keith R.; Yan, Di; Fong, Kean Chern; Kho, Teng C.

    2014-01-01

    Free carrier absorption in heavily doped silicon can have a significant impact on devices operating in the infrared. In the near infrared, the free carrier absorption process can compete with band to band absorption processes, thereby reducing the number of available photons to optoelectronic devices such as solar cells. In this work, we fabricate 18 heavily doped regions by phosphorus and boron diffusion into planar polished silicon wafers; the simple sample structure facilitates accurate and precise measurement of the free carrier absorptance. We measure and model reflectance and transmittance dispersion to arrive at a parameterisation for the free carrier absorption coefficient that applies in the wavelength range between 1000 and 1500 nm, and the range of dopant densities between ∼10 18 and 3 × 10 20  cm −3 . Our measurements indicate that previously published parameterisations underestimate the free carrier absorptance in phosphorus diffusions. On the other hand, published parameterisations are generally consistent with our measurements and model for boron diffusions. Our new model is the first to be assigned uncertainty and is well-suited to routine device analysis

  17. Learning to Facilitate (Online) Meetings

    DEFF Research Database (Denmark)

    Reimann, Peter; Bull, Susan; Vatrapu, Ravi

    2013-01-01

    We describe an approach to teaching collaboration skills directly by building on competences for meeting facilitation. (Online) meetings provide a rich arena to practice collaboration since they can serve multiple purposes: learning, problem solving, decision making, idea generation and advancement...

  18. Facilitative root interactions in intercrops

    DEFF Research Database (Denmark)

    Hauggaard-Nielsen, H.; Jensen, E.S.

    2005-01-01

    of root architecture, exudation of growth stimulating substances, and biofumigation. Facilitative root interactions are most likely to be of importance in nutrient poor soils and in low-input agroecosystems due to critical interspecific competition for plant growth factors. However, studies from more...... nitrogen transfer between legumes and non-leguminous plants, exploitation of the soil via mycorrhizal fungi and soil-plant processes which alter the mobilisation of plant growth resources such as through exudation of amino acids, extra-cellular enzymes, acidification, competition-induced modification......Facilitation takes place when plants ameliorate the environment of their neighbours, and increase their growth and survival. Facilitation occurs in natural ecosystems as well as in agroecosystems. We discuss examples of facilitative root interactions in intercropped agroecosystems; including...

  19. On novice facilitators doing research

    DEFF Research Database (Denmark)

    Tavella, Elena

    2018-01-01

    Opportunities for novices to facilitate Problem Structuring Methods (PSMs) workshops are limited, especially because of a lack of access to real-world interventions and confidence in their capabilities. Novices are usually young academics building their careers through publishing. Publishing...... is challenging if facilitation and opportunities for data collection are limited. To address this challenge, this paper suggests autoethnography as a framework for addressing difficulties that novices face in conducting research and publishing on PSMs. This suggestion grows out of a literature study...

  20. Facilitation Skills for Library Professionals

    OpenAIRE

    O'Shea, Anne; Matheson, Laura

    2010-01-01

    Session summary: Brainstorming, problem-solving, team-building and group communication – all of these things can be made easier through facilitation! Come to this fun, interactive workshop to learn techniques and exercises to boost your group meetings. Taught by two information professionals with formal facilitation training and experience, this workshop will give you theory, hands-on practice time and feedback. What participants will learn: Participants will learn techniques to he...

  1. Subgap Absorption in Conjugated Polymers

    Science.gov (United States)

    Sinclair, M.; Seager, C. H.; McBranch, D.; Heeger, A. J; Baker, G. L.

    1991-01-01

    Along with X{sup (3)}, the magnitude of the optical absorption in the transparent window below the principal absorption edge is an important parameter which will ultimately determine the utility of conjugated polymers in active integrated optical devices. With an absorptance sensitivity of materials. We have used PDS to measure the optical absorption spectra of the conjugated polymers poly(1,4-phenylene-vinylene) (and derivitives) and polydiacetylene-4BCMU in the spectral region from 0.55 eV to 3 eV. Our spectra show that the shape of the absorption edge varies considerably from polymer to polymer, with polydiacetylene-4BCMU having the steepest absorption edge. The minimum absorption coefficients measured varied somewhat with sample age and quality, but were typically in the range 1 cm{sup {minus}1} to 10 cm{sup {minus}1}. In the region below 1 eV, overtones of C-H stretching modes were observed, indicating that further improvements in transparency in this spectral region might be achieved via deuteration of fluorination.

  2. Sabine absorption coefficients to random incidence absorption coefficients

    DEFF Research Database (Denmark)

    Jeong, Cheol-Ho

    2014-01-01

    into random incidence absorption coefficients for porous absorbers are investigated. Two optimization-based conversion methods are suggested: the surface impedance estimation for locally reacting absorbers and the flow resistivity estimation for extendedly reacting absorbers. The suggested conversion methods...

  3. Herb-drug interactions.

    Science.gov (United States)

    Fugh-Berman, A

    2000-01-08

    Concurrent use of herbs may mimic, magnify, or oppose the effect of drugs. Plausible cases of herb-drug interactions include: bleeding when warfarin is combined with ginkgo (Ginkgo biloba), garlic (Allium sativum), dong quai (Angelica sinensis), or danshen (Salvia miltiorrhiza); mild serotonin syndrome in patients who mix St John's wort (Hypericum perforatum) with serotonin-reuptake inhibitors; decreased bioavailability of digoxin, theophylline, cyclosporin, and phenprocoumon when these drugs are combined with St John's wort; induction of mania in depressed patients who mix antidepressants and Panax ginseng; exacerbation of extrapyramidal effects with neuroleptic drugs and betel nut (Areca catechu); increased risk of hypertension when tricyclic antidepressants are combined with yohimbine (Pausinystalia yohimbe); potentiation of oral and topical corticosteroids by liquorice (Glycyrrhiza glabra); decreased blood concentrations of prednisolone when taken with the Chinese herbal product xaio chai hu tang (sho-salko-to); and decreased concentrations of phenytoin when combined with the Ayurvedic syrup shankhapushpi. Anthranoid-containing plants (including senna [Cassia senna] and cascara [Rhamnus purshiana]) and soluble fibres (including guar gum and psyllium) can decrease the absorption of drugs. Many reports of herb-drug interactions are sketchy and lack laboratory analysis of suspect preparations. Health-care practitioners should caution patients against mixing herbs and pharmaceutical drugs.

  4. Absorption factor for cylindrical samples

    International Nuclear Information System (INIS)

    Sears, V.F.

    1984-01-01

    The absorption factor for the scattering of X-rays or neutrons in cylindrical samples is calculated by numerical integration for the case in which the absorption coefficients of the incident and scattered beams are not equal. An extensive table of values having an absolute accuracy of 10 -4 is given in a companion report [Sears (1983). Atomic Energy of Canada Limited, Report No. AECL-8176]. In the present paper an asymptotic expression is derived for the absorption factor which can be used with an error of less than 10 -3 for most cases of interest in both neutron inelastic scattering and neutron diffraction in crystals. (Auth.)

  5. Facilitating RNA structure prediction with microarrays.

    Science.gov (United States)

    Kierzek, Elzbieta; Kierzek, Ryszard; Turner, Douglas H; Catrina, Irina E

    2006-01-17

    Determining RNA secondary structure is important for understanding structure-function relationships and identifying potential drug targets. This paper reports the use of microarrays with heptamer 2'-O-methyl oligoribonucleotides to probe the secondary structure of an RNA and thereby improve the prediction of that secondary structure. When experimental constraints from hybridization results are added to a free-energy minimization algorithm, the prediction of the secondary structure of Escherichia coli 5S rRNA improves from 27 to 92% of the known canonical base pairs. Optimization of buffer conditions for hybridization and application of 2'-O-methyl-2-thiouridine to enhance binding and improve discrimination between AU and GU pairs are also described. The results suggest that probing RNA with oligonucleotide microarrays can facilitate determination of secondary structure.

  6. Drugs in sport.

    Science.gov (United States)

    McGrath, J C; Cowan, D A

    2008-06-01

    This themed issue of the British Journal of Pharmacology has been compiled and edited by Ian McGrath, Regius Professor of Physiology at University of Glasgow and David Cowan, Director of the Drug Control Centre at King's College London. It contains 11 articles covering the mechanisms of action of the major groups of drugs used illicitly in sport. The articles, written by experts in how drugs work, set out where drugs can or cannot affect sporting performance, how this relates to their legitimate medicinal use, their other detrimental effects and how they can be detected. Publication coincides with Olympic year, when sport is highlighted in the public mind and much speculation is made concerning the use of drugs. The articles provide a framework of expert, accurate knowledge to inform and facilitate these debates and to help to overcome the ill-informed and dangerous anecdotal information by which sports men and women are persuaded to misuse drugs in the mistaken belief that this will improve their performance without present or future ill effects. A unique article is included by the Spedding brothers, Mike with a long career in drug discovery and Charlie, the 1984 Los Angeles Olympic Marathon Bronze Medallist and still the English National Marathon record holder. From their unique experience, they describe the insidious and unfair way that drug-assisted performance undermines the ethos of sport and endangers the vital place of sport in maintaining the health of the population.

  7. Drug allergies

    Science.gov (United States)

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... A drug allergy involves an immune response in the body that produces an allergic reaction to a medicine. The first time ...

  8. Study Drugs

    Science.gov (United States)

    ... to quit, they may have withdrawal symptoms like depression, thoughts of suicide, intense drug cravings, sleep problems, and fatigue. The health risks aren't the only downside to study drugs. Students caught with illegal prescription drugs may get suspended ...

  9. Drug Facts

    Medline Plus

    Full Text Available ... symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely to Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard to ...

  10. Drug Facts

    Medline Plus

    Full Text Available ... Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen ... to prescription drugs. The addiction slowly took over his life. I need different people around me. To ...

  11. Drug Reactions

    Science.gov (United States)

    ... problem is interactions, which may occur between Two drugs, such as aspirin and blood thinners Drugs and food, such as statins and grapefruit Drugs and supplements, such as ginkgo and blood thinners ...

  12. Drug Facts

    Science.gov (United States)

    ... Makes Someone More Likely to Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard ... the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol ...

  13. Clinical Drug-Drug Pharmacokinetic Interaction Potential of Sucralfate with Other Drugs: Review and Perspectives.

    Science.gov (United States)

    Sulochana, Suresh P; Syed, Muzeeb; Chandrasekar, Devaraj V; Mullangi, Ramesh; Srinivas, Nuggehally R

    2016-10-01

    Sucralfate, a complex of aluminium hydroxide with sulfated sucrose, forms a strong gastrointestinal tract (GIT) mucosal barrier with excellent anti-ulcer property. Because sucralfate does not undergo any significant oral absorption, sucralfate resides in the GIT for a considerable length of time. The unabsorbed sucralfate may alter the pharmacokinetics of the oral drugs by impeding its absorption and reducing the oral bioavailability. Because of the increased use of sucralfate, it was important to provide a reappraisal of the published clinical drug-drug interaction studies of sucralfate with scores of drugs. This review covers several category of drugs such as non-steroidal anti-inflammatory drugs, fluoroquinolones, histamine H2-receptor blockers, macrolides, anti-fungals, anti-diabetics, salicylic acid derivatives, steroidal anti-inflammatory drugs and provides pharmacokinetic data summary along with study design, objectives and key remarks. While the loss of oral bioavailability was significant for the fluoroquinolone class, it generally varied for other classes of drugs, suggesting that impact of the co-administration of sucralfate is manageable in clinical situations. Given the technology advancement in formulation development, it may be in order feasible to develop appropriate formulation strategies to either avoid or minimize the absorption-related issues when co-administered with sucralfate. It is recommended that consideration of both in vitro and preclinical studies may be in order to gauge the level of interaction of a drug with sucralfate. Such data may aid in the development of appropriate strategies to navigate the co-administration of sucralfate with other drugs in this age of polypharmacy.

  14. OZONE ABSORPTION IN RAW WATERS

    Directory of Open Access Journals (Sweden)

    LJILJANA TAKIĆ

    2008-03-01

    Full Text Available The ozone absorption in raw water entering the main ozonization step at the Belgrade drinking water supply plant was investigated in a continuous stirred tank reactor (CSTR. A slow chemical reaction rate of dissolved ozone and pollutants present in raw water have been experimentally determined. The modified Hatta number was defined and calculated as a criterion which determines whether and to which extent the reactions of ozone and pollutants influence the rate of the pure physical ozone absorption.

  15. Microwaves absorption in superconducting materials

    International Nuclear Information System (INIS)

    Biasi, R.S. de; Fernandes, A.A.R.; Pereira, R.F.R.

    1989-01-01

    Microwaves absorption measures in two superconductors ceramics systems, Y-Ba-Cu-O and Bi-Sr-Ca-Cu-O are compared with similars datas obtained in the same band of temperature by a conventional method, mutual inductance. The results suggest that the microwaves absorption can be used as single and non-destructive method for investigating the properties of ceramics superconductors. (C.G.C.) [pt

  16. Biochemistry of drugs. XXVII

    International Nuclear Information System (INIS)

    Raz, K.; Smolik, S.; Vinarova, M.; Janda, J.; Franc, Z.

    1979-01-01

    The erythro- and threoform of p-hydroxynorephedrine belong to the group of drugs affecting the course of hypertensive disease. For pharmacological studies both forms were labelled with 3 H radionuclide on the benzene ring. 90% of radioactivity was concentrated in the ortho positions with regard to the hydroxyl, 10% in the meta position. After the administration of the labelled drug to rats, rapid absorption occurs and radioactivity is eliminated from the organism, especially in the urine. Three radioactive substances were found in the urine of experimental animals. A substance with properties corresponding to those of the administered drug prevailed. The highest levels of radioactivity in the tissues were found after intravenous administration as early as after 5 minutes after administration, 15 minutes after subcutaneous administration. It was found that p-hydroxynorephedrine significantly restricted the detainment of labelled noradrenaline-7- 3 H in the tissues of premedicated animals. (author)

  17. Facilitation of learning: part 1.

    Science.gov (United States)

    Warburton, Tyler; Trish, Houghton; Barry, Debbie

    2016-04-06

    This article, the fourth in a series of 11, discusses the context for the facilitation of learning. It outlines the main principles and theories for understanding the process of learning, including examples which link these concepts to practice. The practical aspects of using these theories in a practice setting will be discussed in the fifth article of this series. Together, these two articles will provide mentors and practice teachers with knowledge of the learning process, which will enable them to meet the second domain of the Nursing and Midwifery Council's Standards to Support Learning and Assessment in Practice on facilitation of learning.

  18. Confusing the drug facts on one nonprescription drug label with those on another: The Drug Facts Label as a text schema

    Directory of Open Access Journals (Sweden)

    Michael P Ryan

    2016-04-01

    Full Text Available The Drug Facts Label is designed to guide consumers in comparing nonprescription drugs. Undergraduates studied and recalled drug facts for three analgesic or non-analgesic labels using Drug Facts Label headings as retrieval cues. They then studied and recalled drug facts from an aspirin label. Aspirin recall was greater when the prior labels were analgesics, but prior-label intrusion errors were also greater. These two effects were associated with the number of prior drug labels on which facilitating and interfering drug facts appeared. Using the Drug Facts Label schema to read drug labels can both enhance and degrade the recall of nonprescription drug facts.

  19. Ultrasonic absorption in solid specimens

    International Nuclear Information System (INIS)

    Siwabessy, P.J. W.; Stewart, G.A.

    1996-01-01

    As part of a project to measure the absorption of high frequency (50 - 500 kHz) sonar signals in warm sea-water, a laboratory apparatus has been constructed and tested against room temperature distilled water and various solutions of MgSO 4 (chemical relaxation of MgSO 4 is the major contribution to absorption below 200 kHz). The technique involves monitoring the decay of an acoustic signal for different sizes of vessels of water suspended in an evacuated chamber. So far, all containing vessels used have been spherical in shape. Extrapolation of the results to infinite volume yields the absorption due to the water alone. In order to accommodate variations in temperature and pressure, and to make the system more robust (e.g. for ship deck usage), it is desirable to employ stainless steel vessels. However, it was found that the quality of the data was greatly improved when pyrex glass spheres were used. The stainless steel spheres were manufactured by welding together mechanically spun hemispheres. The linear frequency dependence characteristic of acoustic absorption in solids was observed (in contrast to the quadratic frequency dependence of acoustic absorption in water), and the acoustic absorption was found to depend strongly on the thermal history of the steel

  20. DRUG-INTERACTIONS WITH QUINOLONE ANTIBACTERIALS

    NARCIS (Netherlands)

    BROUWERS, JRBJ

    1992-01-01

    The quinolone antibacterials are prone to many interactions with other drugs. Quinolone absorption is markedly reduced with antacids containing aluminium, magnesium and/or calcium and therapeutic failure may result. Other metallic ion-containing drugs, such as sucralfate, iron salts, and zinc salts,

  1. Facilitation of Mourning During Childhood.

    Science.gov (United States)

    Kliman, Gilbert; And Others

    This paper discusses case studies of children psychologically disturbed by the death of parents or siblings. Illustrations of mourning facilitation were mainly gathered from 16 orphaned children, ages 3-14. Some techniques used in helping children mourn include: discussing physical details of the illness, discussing previous deaths of animals and…

  2. Brug af mindfulness til facilitering

    DEFF Research Database (Denmark)

    Adriansen, Hanne Kirstine; Krohn, Simon

    2011-01-01

    Gennem de senere år er mindfulness gået fra udelukkende at være en eksistentiel praksis til også at være en behandlingsform og senest til også at blive brugt som et praktisk redskab i erhvervslivet. Denne artikel viser, at mindfulness også kan anvendes i forbindelse med facilitering. Facilitering...... er et værktøj, som bruges i arbejdslivet fx til møder og konferencer, hvor en gruppe mennesker er samlet for at lære eller udrette noget sammen. Det nye ved at kombinere mindfulness med facilitering er, at fokus hermed ændres fra individet, som er centrum for den eksistentielle fordybelse eller det...... terapeutiske forløb, til gruppen, som er udgangspunktet i facilitering. Artiklen viser, hvordan mindfulness konkret kan bruges på gruppeniveau og diskuterer samtidig hvilke problemer, der kan være forbundet hermed. Baseret på vores egne erfaringer, diskuterer vi, hvordan mindfulness kan påvirke en gruppes...

  3. Facilitating Conversations about Managerial Identities

    DEFF Research Database (Denmark)

    Madsen, Mona Toft

    -based organization in the engineering consulting sector b) a reflection meeting, where the same three managers were gathered, and conversations were facilitated based on identity work in the context of earlier interviews. More specifically, three themes were discussed; flat organizational structure, tensions between...

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

    Directory of Open Access Journals (Sweden)

    Miteva Maria A

    2008-09-01

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

  5. Emerging Frontiers in Drug Delivery.

    Science.gov (United States)

    Tibbitt, Mark W; Dahlman, James E; Langer, Robert

    2016-01-27

    Medicine relies on the use of pharmacologically active agents (drugs) to manage and treat disease. However, drugs are not inherently effective; the benefit of a drug is directly related to the manner by which it is administered or delivered. Drug delivery can affect drug pharmacokinetics, absorption, distribution, metabolism, duration of therapeutic effect, excretion, and toxicity. As new therapeutics (e.g., biologics) are being developed, there is an accompanying need for improved chemistries and materials to deliver them to the target site in the body, at a therapeutic concentration, and for the required period of time. In this Perspective, we provide an historical overview of drug delivery and controlled release followed by highlights of four emerging areas in the field of drug delivery: systemic RNA delivery, drug delivery for localized therapy, oral drug delivery systems, and biologic drug delivery systems. In each case, we present the barriers to effective drug delivery as well as chemical and materials advances that are enabling the field to overcome these hurdles for clinical impact.

  6. Nasal Delivery of High Molecular Weight Drugs

    Directory of Open Access Journals (Sweden)

    Erdal Cevher

    2009-09-01

    Full Text Available Nasal drug delivery may be used for either local or systemic effects. Low molecular weight drugs with are rapidly absorbed through nasal mucosa. The main reasons for this are the high permeability, fairly wide absorption area, porous and thin endothelial basement membrane of the nasal epithelium. Despite the many advantages of the nasal route, limitations such as the high molecular weight (HMW of drugs may impede drug absorption through the nasal mucosa. Recent studies have focused particularly on the nasal application of HMW therapeutic agents such as peptide-protein drugs and vaccines intended for systemic effects. Due to their hydrophilic structure, the nasal bioavailability of peptide and protein drugs is normally less than 1%. Besides their weak mucosal membrane permeability and enzymatic degradation in nasal mucosa, these drugs are rapidly cleared from the nasal cavity after administration because of mucociliary clearance. There are many approaches for increasing the residence time of drug formulations in the nasal cavity resulting in enhanced drug absorption. In this review article, nasal route and transport mechanisms across the nasal mucosa will be briefly presented. In the second part, current studies regarding the nasal application of macromolecular drugs and vaccines with nanoand micro-particulate carrier systems will be summarised.

  7. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use and HIV/AIDS Treatment & Recovery Why Does a Person Need Treatment? Does Drug Treatment Work? What Are the Treatment Options? What Is Recovery? ...

  8. Drug Facts

    Medline Plus

    Full Text Available ... 4357) at any time to find drug treatment centers near you. I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her daughter to stay away from drugs. But she's afraid ...

  9. Erbium-yttrium-aluminum-garnet laser irradiation ameliorates skin permeation and follicular delivery of antialopecia drugs.

    Science.gov (United States)

    Lee, Woan-Ruoh; Shen, Shing-Chuan; Aljuffali, Ibrahim A; Li, Yi-Ching; Fang, Jia-You

    2014-11-01

    Alopecia usually cannot be cured because of the available drug therapy being unsatisfactory. To improve the efficiency of treatment, erbium-yttrium-aluminum-garnet (Er-YAG) laser treatment was conducted to facilitate skin permeation of antialopecia drugs such as minoxidil (MXD), diphencyprone (DPCP), and peptide. In vitro and in vivo percutaneous absorption experiments were carried out by using nude mouse skin and porcine skin as permeation barriers. Fluorescence and confocal microscopies were used to visualize distribution of permeants within the skin. Laser ablation at a depth of 6 and 10 μm enhanced MXD skin accumulation twofold to ninefold depending on the skin barriers selected. DPCP absorption showed less enhancement by laser irradiation as compared with MXD. An ablation depth of 10 μm could increase the peptide flux from zero to 4.99 and 0.33 μg cm(-2) h(-1) for nude mouse skin and porcine skin, respectively. The laser treatment also promoted drug uptake in the hair follicles, with DPCP demonstrating the greatest enhancement (sixfold compared with the control). The imaging of skin examined by microscopies provided evidence of follicular and intercellular delivery assisted by the Er-YAG laser. Besides the ablative effect of removing the stratum corneum, the laser may interact with sebum to break up the barrier function, increasing the skin delivery of antialopecia drugs. The minimally invasive, well-controlled approach of laser-mediated drug permeation offers a potential way to treat alopecia. This study's findings provide the basis for the first report on laser-assisted delivery of antialopecia drugs. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  10. Absorption and Clearance of Pharmaceutical Aerosols in the Human Nose: Effects of Nasal Spray Suspension Particle Size and Properties.

    Science.gov (United States)

    Rygg, Alex; Hindle, Michael; Longest, P Worth

    2016-04-01

    The objective of this study was to use a recently developed nasal dissolution, absorption, and clearance (DAC) model to evaluate the extent to which suspended drug particle size influences nasal epithelial drug absorption for a spray product. Computational fluid dynamics (CFD) simulations of mucociliary clearance and drug dissolution were used to calculate total and microscale epithelial absorption of drug delivered with a nasal spray pump. Ranges of suspended particle sizes, drug solubilities, and partition coefficients were evaluated. Considering mometasone furoate as an example, suspended drug particle sizes in the range of 1-5 μm did not affect the total nasal epithelial uptake. However, the microscale absorption of suspended drug particles with low solubilities was affected by particle size and this controlled the extent to which the drug penetrated into the distal nasal regions. The nasal-DAC model was demonstrated to be a useful tool in determining the nasal exposure of spray formulations with different drug particle sizes and solubilities. Furthermore, the model illustrated a new strategy for topical nasal drug delivery in which drug particle size is selected to increase the region of epithelial surface exposure using mucociliary clearance while minimizing the drug dose exiting the nasopharynx.

  11. Absorption properties of identical atoms

    International Nuclear Information System (INIS)

    Sancho, Pedro

    2013-01-01

    Emission rates and other optical properties of multi-particle systems in collective and entangled states differ from those in product ones. We show the existence of similar effects in the absorption probabilities for (anti)symmetrized states of two identical atoms. The effects strongly depend on the overlapping between the atoms and differ for bosons and fermions. We propose a viable experimental verification of these ideas. -- Highlights: •The absorption rates of a pair of identical atoms in product and (anti)symmetrized states are different. •The modifications of the optical properties are essentially determined by the overlapping between the atoms. •The absorption properties differ, in some cases, for bosons and fermions

  12. Architecture for Absorption Based Heaters

    Science.gov (United States)

    Moghaddam, Saeed; Chugh, Devesh

    2018-04-24

    An absorption based heater is constructed on a fluid barrier heat exchanging plate such that it requires little space in a structure. The absorption based heater has a desorber, heat exchanger, and absorber sequentially placed on the fluid barrier heat exchanging plate. The vapor exchange faces of the desorber and the absorber are covered by a vapor permeable membrane that is permeable to a refrigerant vapor but impermeable to an absorbent. A process fluid flows on the side of the fluid barrier heat exchanging plate opposite the vapor exchange face through the absorber and subsequently through the heat exchanger. The absorption based heater can include a second plate with a condenser situated parallel to the fluid barrier heat exchanging plate and opposing the desorber for condensation of the refrigerant for additional heating of the process fluid.

  13. Mercury absorption in aqueous hypochlorite

    International Nuclear Information System (INIS)

    Zhao, L.L.; Rochelle, G.T.

    1999-01-01

    The absorption of elemental Hg vapor into aqueous hypochlorite was measured in a stirred tank reactor at 25 and 55C. NaOCl strongly absorbs Hg even at high pH. Low pH, high Cl - and high-temperature favor mercury absorption. Aqueous free Cl 2 was the active species that reacted with mercury. However, chlorine desorption was evident at high Cl - and pH 15 M -1 s -1 at 25C and 1.4x10 17 M -1 s -1 at 55C. Gas-phase reaction was observed between Hg and Cl 2 on apparatus surfaces. Strong mercury absorption in water was also detected with Cl 2 present. Results indicate that the chlorine concentration, moisture, and surface area contribute positively to mercury removal. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  14. Phytases for improved iron absorption

    DEFF Research Database (Denmark)

    Nielsen, Anne Veller Friis; Meyer, Anne S.

    2016-01-01

    Phytase enzymes present an alternative to iron supplements, because they have been shown to improve iron absorption by means of catalysing the degradation of a potent iron absorption inhibitor: phytic acid. Phytic acid is a hexaphosphate of inositol and is particularly prevalent in cereal grains......, where it serves as a storage molecule for phosphorous. Phytic acid is also associated with minerals. The minerals are bound by chelation to the negatively charged phosphate groups in phytic acid. Phytases catalyse the dephosphorylation of phytic acid, thus releasing bound minerals to make them available...... for absorption. This article presents research on phytase catalysis in gastric conditions and considers potential benefits and drawbacks for using phytases as a food supplement....

  15. Semantic Coherence Facilitates Distributional Learning.

    Science.gov (United States)

    Ouyang, Long; Boroditsky, Lera; Frank, Michael C

    2017-04-01

    Computational models have shown that purely statistical knowledge about words' linguistic contexts is sufficient to learn many properties of words, including syntactic and semantic category. For example, models can infer that "postman" and "mailman" are semantically similar because they have quantitatively similar patterns of association with other words (e.g., they both tend to occur with words like "deliver," "truck," "package"). In contrast to these computational results, artificial language learning experiments suggest that distributional statistics alone do not facilitate learning of linguistic categories. However, experiments in this paradigm expose participants to entirely novel words, whereas real language learners encounter input that contains some known words that are semantically organized. In three experiments, we show that (a) the presence of familiar semantic reference points facilitates distributional learning and (b) this effect crucially depends both on the presence of known words and the adherence of these known words to some semantic organization. Copyright © 2016 Cognitive Science Society, Inc.

  16. Characteristic sounds facilitate visual search.

    Science.gov (United States)

    Iordanescu, Lucica; Guzman-Martinez, Emmanuel; Grabowecky, Marcia; Suzuki, Satoru

    2008-06-01

    In a natural environment, objects that we look for often make characteristic sounds. A hiding cat may meow, or the keys in the cluttered drawer may jingle when moved. Using a visual search paradigm, we demonstrated that characteristic sounds facilitated visual localization of objects, even when the sounds carried no location information. For example, finding a cat was faster when participants heard a meow sound. In contrast, sounds had no effect when participants searched for names rather than pictures of objects. For example, hearing "meow" did not facilitate localization of the word cat. These results suggest that characteristic sounds cross-modally enhance visual (rather than conceptual) processing of the corresponding objects. Our behavioral demonstration of object-based cross-modal enhancement complements the extensive literature on space-based cross-modal interactions. When looking for your keys next time, you might want to play jingling sounds.

  17. A facile nanoaggregation strategy for oral delivery of hydrophobic drugs by utilizing acid-base neutralization reactions

    International Nuclear Information System (INIS)

    Chen Huabing; Wan Jiangling; Wang Yirui; Mou Dongsheng; Liu Hongbin; Xu Huibi; Yang Xiangliang

    2008-01-01

    Nanonization strategies have been used to enhance the oral availability of numerous drugs that are poorly soluble in water. Exploring a facile nanonization strategy with highly practical potential is an attractive focus. Here, we report a novel facile nanoaggregation strategy for constructing drug nanoparticles of poorly soluble drugs with pH-dependent solubility by utilizing acid-base neutralization in aqueous solution, thus facilitating the exploration of nanonization in oral delivery for general applicability. We demonstrate that hydrophobic itraconazole dissolved in acid solution formed a growing core and aggregated into nanoparticles in the presence of stabilizers. The nanoparticles, with an average diameter of 279.3 nm and polydispersity index of 0.116, showed a higher dissolution rate when compared with the marketed formulation; the average dissolution was about 91.3%. The in vivo pharmacokinetic studies revealed that the nanoparticles had a rapid absorption and enhanced oral availability. The diet state also showed insignificant impact on the absorption of itraconazole from nanoparticles. This nanoaggregation strategy is a promising nanonization method with a facile process and avoidance of toxic organic solvents for oral delivery of poorly soluble drugs with pH-dependent solubility and reveals a highly practical potential in the pharmaceutical and chemical industries

  18. Soluble polymer conjugates for drug delivery.

    Science.gov (United States)

    Minko, Tamara

    2005-01-01

    The use of water-soluble polymeric conjugates as drug carriers offers several possible advantages. These advantages include: (1) improved drug pharmacokinetics; (2) decreased toxicity to healthy organs; (3) possible facilitation of accumulation and preferential uptake by targeted cells; (4) programmed profile of drug release. In this review, we will consider the main types of useful polymeric conjugates and their role and effectiveness as carriers in drug delivery systems.: © 2005 Elsevier Ltd . All rights reserved.

  19. The effects of three absorption-modifying critical excipients on the in vivo intestinal absorption of six model compounds in rats and dogs.

    Science.gov (United States)

    David, Dahlgren; Carl, Roos; Pernilla, Johansson; Christer, Tannergren; Anders, Lundqvist; Peter, Langguth; Markus, Sjöblom; Erik, Sjögren; Hans, Lennernäs

    2018-05-11

    Pharmaceutical excipients that may affect gastrointestinal (GI) drug absorption are called critical pharmaceutical excipients (CPEs), or absorption-modifying excipients (AMEs) if they act by altering the integrity of the intestinal epithelial cell membrane. Some of these excipients increase intestinal permeability, and subsequently the absorption and bioavailability of the drug. This could have implications for both the assessment of bioequivalence and the efficacy of the absorption-enhancing drug delivery system. The absorption-enhancing effects of AMEs/CPEs with different mechanisms (chitosan, sodium caprate, sodium dodecyl sulfate (SDS)) have previously been evaluated in the rat single-pass intestinal perfusion (SPIP) model. However, it remains unclear whether these SPIP data are predictive in a more in vivo like model. The same excipients were in this study evaluated in rat and dog intraintestinal bolus models. SDS and chitosan did exert an absorption-enhancing effect in both bolus models, but the effect was substantially lower than those observed in the rat SPIP model. This illustrates the complexity of the AME/CPE effects, and indicates that additional GI physiological factors need to be considered in their evaluation. We therefore recommend that AME/CPE evaluations obtained in transit-independent, preclinical permeability models (e.g. Ussing, SPIP) should be verified in animal models better able to predict in vivo relevant GI effects, at multiple excipient concentrations. Copyright © 2018. Published by Elsevier B.V.

  20. Absorption-heat-pump system

    Science.gov (United States)

    Grossman, G.; Perez-Blanco, H.

    1983-06-16

    An improvement in an absorption heat pump cycle is obtained by adding adiabatic absorption and desorption steps to the absorber and desorber of the system. The adiabatic processes make it possible to obtain the highest temperature in the absorber before any heat is removed from it and the lowest temperature in the desorber before heat is added to it, allowing for efficient utilization of the thermodynamic availability of the heat supply stream. The improved system can operate with a larger difference between high and low working fluid concentrations, less circulation losses, and more efficient heat exchange than a conventional system.

  1. Absorption Efficiency of Receiving Antennas

    DEFF Research Database (Denmark)

    Andersen, Jørgen Bach; Frandsen, Aksel

    2005-01-01

    A receiving antenna with a matched load will always scatter some power. This paper sets an upper and a lower bound on the absorption efficiency (absorbed power over sum of absorbed and scattered powers), which lies between 0 and 100% depending on the directivities of the antenna and scatter...... patterns. It can approach 100% as closely as desired, although in practice this may not be an attractive solution. An example with a small endfire array of dipoles shows an efficiency of 93%. Several examples of small conical horn antennas are also given, and they all have absorption efficiencies less than...

  2. Aerosol Absorption Measurements in MILAGRO.

    Science.gov (United States)

    Gaffney, J. S.; Marley, N. A.; Arnott, W. P.; Paredes-Miranda, L.; Barnard, J. C.

    2007-12-01

    During the month of March 2006, a number of instruments were used to determine the absorption characteristics of aerosols found in the Mexico City Megacity and nearby Valley of Mexico. These measurements were taken as part of the Department of Energy's Megacity Aerosol Experiment - Mexico City (MAX-Mex) that was carried out in collaboration with the Megacity Interactions: Local and Global Research Observations (MILAGRO) campaign. MILAGRO was a joint effort between the DOE, NSF, NASA, and Mexican agencies aimed at understanding the impacts of a megacity on the urban and regional scale. A super-site was operated at the Instituto Mexicano de Petroleo in Mexico City (designated T-0) and at the Universidad Technologica de Tecamac (designated T-1) that was located about 35 km to the north east of the T-0 site in the State of Mexico. A third site was located at a private rancho in the State of Hidalgo approximately another 35 km to the northeast (designated T-2). Aerosol absorption measurements were taken in real time using a number of instruments at the T-0 and T-1 sites. These included a seven wavelength aethalometer, a multi-angle absorption photometer (MAAP), and a photo-acoustic spectrometer. Aerosol absorption was also derived from spectral radiometers including a multi-filter rotating band spectral radiometer (MFRSR). The results clearly indicate that there is significant aerosol absorption by the aerosols in the Mexico City megacity region. The absorption can lead to single scattering albedo reduction leading to values below 0.5 under some circumstances. The absorption is also found to deviate from that expected for a "well-behaved" soot anticipated from diesel engine emissions, i.e. from a simple 1/lambda wavelength dependence for absorption. Indeed, enhanced absorption is seen in the region of 300-450 nm in many cases, particularly in the afternoon periods indicating that secondary organic aerosols are contributing to the aerosol absorption. This is likely due

  3. Substance use - prescription drugs

    Science.gov (United States)

    Substance use disorder - prescription drugs; Substance abuse - prescription drugs; Drug abuse - prescription drugs; Drug use - prescription drugs; Narcotics - substance use; Opioid - substance use; Sedative - substance ...

  4. Effective photons in weakly absorptive dielectric media and the Beer–Lambert–Bouguer law

    International Nuclear Information System (INIS)

    Judge, A C; Brownless, J S; Martijn de Sterke, C; Bhat, N A R; Sipe, J E; Steel, M J

    2014-01-01

    We derive effective photon modes that facilitate an intuitive and convenient picture of photon dynamics in a structured Kramers–Kronig dielectric in the limit of weak absorption. Each mode is associated with a mode field distribution that includes the effects of both material and structural dispersion, and an effective line-width that determines the temporal decay rate of the photon. These results are then applied to obtain an expression for the Beer–Lambert–Bouguer law absorption coefficient for unidirectional propagation in structured media consisting of dispersive, weakly absorptive dielectric materials

  5. Future of the transdermal drug delivery market--have we barely touched the surface?

    Science.gov (United States)

    Watkinson, Adam C; Kearney, Mary-Carmel; Quinn, Helen L; Courtenay, Aaron J; Donnelly, Ryan F

    2016-01-01

    Transdermal drug delivery is the movement of drugs across the skin for absorption into the systemic circulation. Transfer of the drug can occur via passive or active means; passive transdermal products do not disrupt the stratum corneum to facilitate delivery whereas active technologies do. Due to the very specific physicochemical properties necessary for successful passive transdermal drug delivery, this sector of the pharmaceutical industry is relatively small. There are many well-documented benefits of this delivery route however, and as a result there is great interest in increasing the number of therapeutic substances that can be delivered transdermally. This review discusses the various transdermal products that are currently/have been marketed, and the paths that led to their success, or lack of. Both passive and active transdermal technologies are considered with the advantages and limitations of each highlighted. In addition to marketed products, technologies that are in the investigative stages by various pharmaceutical companies are reviewed. Passive transdermal drug delivery has made limited progress in recent years, however with the ongoing intense research into active technologies, there is great potential for growth within the transdermal delivery market. A number of active technologies have already been translated into marketed products, with other platforms including microneedles, rapidly progressing towards commercialisation.

  6. Peptide- and saccharide-conjugated dendrimers for targeted drug delivery: a concise review

    Science.gov (United States)

    Liu, Jie; Gray, Warren D.; Davis, Michael E.; Luo, Ying

    2012-01-01

    Dendrimers comprise a category of branched materials with diverse functions that can be constructed with defined architectural and chemical structures. When decorated with bioactive ligands made of peptides and saccharides through peripheral chemical groups, dendrimer conjugates are turned into nanomaterials possessing attractive binding properties with the cognate receptors. At the cellular level, bioactive dendrimer conjugates can interact with cells with avidity and selectivity, and this function has particularly stimulated interests in investigating the targeting potential of dendrimer materials for the design of drug delivery systems. In addition, bioactive dendrimer conjugates have so far been studied for their versatile capabilities to enhance stability, solubility and absorption of various types of therapeutics. This review presents a brief discussion on three aspects of the recent studies to use peptide- and saccharide-conjugated dendrimers for drug delivery: (i) synthesis methods, (ii) cell- and tissue-targeting properties and (iii) applications of conjugated dendrimers in drug delivery nanodevices. With more studies to elucidate the structure–function relationship of ligand–dendrimer conjugates in transporting drugs, the conjugated dendrimers hold promise to facilitate targeted delivery and improve drug efficacy for discovery and development of modern pharmaceutics. PMID:23741608

  7. Drug metabolism and pharmacokinetic diversity of ranunculaceae medicinal compounds.

    Science.gov (United States)

    Hao, Da-Cheng; Ge, Guang-Bo; Xiao, Pei-Gen; Wang, Ping; Yang, Ling

    2015-01-01

    The wide-reaching distributed angiosperm family Ranunculaceae has approximately 2200 species in around 60 genera. Chemical components of this family include several representative groups: benzylisoquinoline alkaloid (BIA), ranunculin, triterpenoid saponin and diterpene alkaloid, etc. Their extensive clinical utility has been validated by traditional uses of thousands of years and current evidence-based medicine studies. Drug metabolism and pharmacokinetic (DMPK) studies of plant-based natural products are an indispensable part of comprehensive medicinal plant exploration, which could facilitate conservation and sustainable utilization of Ranunculaceae pharmaceutical resources, as well as new chemical entity development with improved DMPK parameters. However, DMPK characteristics of Ranunculaceaederived medicinal compounds have not been summarized. Black cohosh (Cimicifuga) and goldenseal (Hydrastis) raise concerns of herbdrug interaction. DMPK studies of other Ranunculaceae genera, e.g., Nigella, Delphinium, Aconitum, Trollius, and Coptis, are also rapidly increasing and becoming more and more clinically relevant. In this contribution, we highlight the up-to-date awareness, as well as the challenges around the DMPK-related issues in optimization of drug development and clinical practice of Ranunculaceae compounds. Herb-herb interaction of Ranunculaceae herb-containing traditional Chinese medicine (TCM) formula could significantly influence the in vivo pharmacokinetic behavior of compounds thereof, which may partially explain the complicated therapeutic mechanism of TCM formula. Although progress has been made on revealing the absorption, distribution, metabolism, excretion and toxicity (ADME/T) of Ranunculaceae compounds, there is a lack of DMPK studies of traditional medicinal genera Aquilegia, Thalictrum and Clematis. Fluorescent probe compounds could be promising substrate, inhibitor and/or inducer in future DMPK studies of Ranunculaceae compounds. A better

  8. Role enactment of facilitation in primary care

    DEFF Research Database (Denmark)

    Due, Tina Drud; Thorsen, Thorkil; Waldorff, Frans Boch

    2017-01-01

    facilitation visits in 13 practice settings and had interviews and focus groups with facilitators. We applied an explorative approach in data collection and analysis, and conducted an inductive thematic analysis. RESULTS: The facilitators mainly enacted four facilitator roles: teacher, super user, peer...

  9. Role enactment of facilitation in primary care

    DEFF Research Database (Denmark)

    Due, Tina Drud; Thorsen, Thorkil; Waldorff, Frans Boch

    2017-01-01

    facilitation visits in 13 practice settings and had interviews and focus groups with facilitators. We applied an explorative approach in data collection and analysis, and conducted an inductive thematic analysis. Results: The facilitators mainly enacted four facilitator roles: teacher, super user, peer...

  10. Konference Distillation and Absorption 2010

    Czech Academy of Sciences Publication Activity Database

    Bendová, Magdalena

    2009-01-01

    Roč. 103, č. 10 (2009), s. 862 ISSN 0009-2770 R&D Projects: GA MŠk LA320 Institutional research plan: CEZ:AV0Z40720504 Keywords : conference * announcement * distillation and absorption Subject RIV: CF - Physical ; Theoretical Chemistry

  11. Gamm-ray absorption techniques

    International Nuclear Information System (INIS)

    Charlton, J.S.

    1986-01-01

    In this chapter the principles of gamma-ray absorption are described and important applications in plant and process techniques such as measurement of thickness of deposits on pipes, checking for voids in concrete, metal corrosion, measurement of the density of materials inside vessels in industrial radiography are discussed. (U.K.)

  12. Emission and absorption of radiation

    International Nuclear Information System (INIS)

    Fetter, S.

    1992-01-01

    A full understanding of fissile-material detection requires a solid knowledge of nuclear physics, especially the emission and absorption of radiation. The purpose of this paper is therefore to give a brief explanation of these processes so that the reader can better understand the assumptions leading to the results in the main text

  13. GIS-facilitated spatial narratives

    DEFF Research Database (Denmark)

    Møller-Jensen, Lasse; Jeppesen, Henrik; Kofie, Richard Y.

    2008-01-01

    on the thematically and narrative linking of a set of locations within an area. A spatial narrative that describes the - largely unsuccessful - history of Danish plantations on the Gold Coast (1788-1850) is implemented through the Google Earth client. This client is seen both as a type of media in itself for ‘home......-based' exploration of sites related to the narrative and as a tool that facilitates the design of spatial narratives before implementation within portable GIS devices. The Google Earth-based visualization of the spatial narrative is created by a Python script that outputs a web-accessible KML format file. The KML...

  14. Drug Facts

    Medline Plus

    Full Text Available ... abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can ...

  15. Prescription Drugs

    Science.gov (United States)

    ... different competition is going on: the National Football League (NFL) vs. drug use. Read More » 92 Comments ... Future survey highlights drug use trends among the Nation’s youth for marijuana, alcohol, cigarettes, e-cigarettes (e- ...

  16. Drug Facts

    Medline Plus

    Full Text Available ... abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth ... 662-HELP (4357) at any time to find drug treatment centers near you. I want my daughter ...

  17. Drug Facts

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    Full Text Available ... form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts ... addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain ...

  18. Drug Facts

    Medline Plus

    Full Text Available ... Ice) Facts Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of ... Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1- ...

  19. Drug Control

    Science.gov (United States)

    Leviton, Harvey S.

    1975-01-01

    This article attempts to assemble pertinent information about the drug problem, particularily marihuana. It also focuses on the need for an educational program for drug control with the public schools as the main arena. (Author/HMV)

  20. Drug Facts

    Medline Plus

    Full Text Available ... Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs ... Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call ...

  1. Drug Facts

    Medline Plus

    Full Text Available ... Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of someone ... use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely to Get Addicted ...

  2. Drug Facts

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    Full Text Available ... Numbers and Websites Search Share Listen English Español Information about this page Click on the button that ... about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana ...

  3. Drug Facts

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    Full Text Available ... Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) ... treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice ( ...

  4. Drug Facts

    Medline Plus

    Full Text Available ... call 1-800-662-HELP (4357) at any time to find drug treatment centers near you. I ... The National Institute on Drug Abuse (NIDA) is part of the National Institutes of Health (NIH) , the ...

  5. High-throughput liquid-absorption air-sampling apparatus and methods

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-07-11

    A portable high-throughput liquid-absorption air sampler [PHTLAAS] has an asymmetric air inlet through which air is drawn upward by a small and light-weight centrifugal fan driven by a direct current motor that can be powered by a battery. The air inlet is so configured as to impart both rotational and downward components of motion to the sampled air near said inlet. The PHTLAAS comprises a glass tube of relatively small size through which air passes at a high rate in a swirling, highly turbulent motion, which facilitates rapid transfer of vapors and particulates to a liquid film covering the inner walls of the tube. The pressure drop through the glass tube is < 10 cm of water, usually < 5 cm of water. The sampler's collection efficiency is usually > 20% for vapors or airborne particulates in the 2--3 microns range and > 50% for particles larger than 4 microns. In conjunction with various analyzers, the PHTLAAS can serve to monitor a variety of hazardous or illicit airborne substances, such as lead-containing particulates, tritiated water vapor, biological aerosols, or traces of concealed drugs or explosives.

  6. High-throughput liquid-absorption air-sampling apparatus and methods

    Science.gov (United States)

    Zaromb, Solomon

    2000-01-01

    A portable high-throughput liquid-absorption air sampler [PHTLAAS] has an asymmetric air inlet through which air is drawn upward by a small and light-weight centrifugal fan driven by a direct current motor that can be powered by a battery. The air inlet is so configured as to impart both rotational and downward components of motion to the sampled air near said inlet. The PHTLAAS comprises a glass tube of relatively small size through which air passes at a high rate in a swirling, highly turbulent motion, which facilitates rapid transfer of vapors and particulates to a liquid film covering the inner walls of the tube. The pressure drop through the glass tube is 20% for vapors or airborne particulates in the 2-3.mu. range and >50% for particles larger than 4.mu.. In conjunction with various analyzers, the PHTLAAS can serve to monitor a variety of hazardous or illicit airborne substances, such as lead-containing particulates, tritiated water vapor, biological aerosols, or traces of concealed drugs or explosives.

  7. High-throughput liquid-absorption air-sampling apparatus and methods

    International Nuclear Information System (INIS)

    2000-01-01

    A portable high-throughput liquid-absorption air sampler [PHTLAAS] has an asymmetric air inlet through which air is drawn upward by a small and light-weight centrifugal fan driven by a direct current motor that can be powered by a battery. The air inlet is so configured as to impart both rotational and downward components of motion to the sampled air near said inlet. The PHTLAAS comprises a glass tube of relatively small size through which air passes at a high rate in a swirling, highly turbulent motion, which facilitates rapid transfer of vapors and particulates to a liquid film covering the inner walls of the tube. The pressure drop through the glass tube is 20% for vapors or airborne particulates in the 2--3 microns range and > 50% for particles larger than 4 microns. In conjunction with various analyzers, the PHTLAAS can serve to monitor a variety of hazardous or illicit airborne substances, such as lead-containing particulates, tritiated water vapor, biological aerosols, or traces of concealed drugs or explosives

  8. Orphan drugs

    OpenAIRE

    Goločorbin-Kon, Svetlana; Vojinović, Aleksandra; Lalić-Popović, Mladena; Pavlović, Nebojša; Mikov, Momir

    2013-01-01

    Introduction. Drugs used for treatment of rare diseases are known worldwide under the term of orphan drugs because pharmaceutical companies have not been interested in ”adopting” them, that is in investing in research, developing and producing these drugs. This kind of policy has been justified by the fact that these drugs are targeted for small markets, that only a small number of patients is available for clinical trials, and that large investments are required for the development of ...

  9. Converting Sabine absorption coefficients to random incidence absorption coefficients

    DEFF Research Database (Denmark)

    Jeong, Cheol-Ho

    2013-01-01

    are suggested: An optimization method for the surface impedances for locally reacting absorbers, the flow resistivity for extendedly reacting absorbers, and the flow resistance for fabrics. With four porous type absorbers, the conversion methods are validated. For absorbers backed by a rigid wall, the surface...... coefficients to random incidence absorption coefficients are proposed. The overestimations of the Sabine absorption coefficient are investigated theoretically based on Miki's model for porous absorbers backed by a rigid wall or an air cavity, resulting in conversion factors. Additionally, three optimizations...... impedance optimization produces the best results, while the flow resistivity optimization also yields reasonable results. The flow resistivity and flow resistance optimization for extendedly reacting absorbers are also found to be successful. However, the theoretical conversion factors based on Miki's model...

  10. Drug Testing

    Science.gov (United States)

    ... testing, substance abuse testing, toxicology screen, tox screen, sports doping tests What is it used for? Drug screening is used to find out whether or not a person has taken a certain drug or drugs. It ... Sports organizations. Professional and collegiate athletes usually need to ...

  11. Drug Facts

    Medline Plus

    Full Text Available ... to main content Easy-to-Read Drug Facts Search form Search Menu Home Drugs That People Abuse Alcohol Facts ... Past Drug Use Prevention Phone Numbers and Websites Search Share Listen English Español Information about this page ...

  12. Drug Facts

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    Full Text Available ... can call 1-800-662-HELP (4357) at any time to find drug treatment centers near you. I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her daughter to stay away from ...

  13. Drug Facts

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    Full Text Available ... the computer will read the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos ... I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her daughter to stay away from ...

  14. Drug Facts

    Medline Plus

    Full Text Available ... the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs ... adicción. English Español About the National Institute on Drug Abuse (NIDA) | About This Website Tools and Resources | Contact ...

  15. Drug Facts

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    Full Text Available ... Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use and HIV/AIDS Treatment & Recovery Why Does a Person Need Treatment? Does Drug Treatment Work? What Are the Treatment Options? What Is Recovery? ...

  16. Drug Facts

    Medline Plus

    Full Text Available ... Makes Someone More Likely to Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard ... the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol ...

  17. Voice congruency facilitates word recognition.

    Directory of Open Access Journals (Sweden)

    Sandra Campeanu

    Full Text Available Behavioral studies of spoken word memory have shown that context congruency facilitates both word and source recognition, though the level at which context exerts its influence remains equivocal. We measured event-related potentials (ERPs while participants performed both types of recognition task with words spoken in four voices. Two voice parameters (i.e., gender and accent varied between speakers, with the possibility that none, one or two of these parameters was congruent between study and test. Results indicated that reinstating the study voice at test facilitated both word and source recognition, compared to similar or no context congruency at test. Behavioral effects were paralleled by two ERP modulations. First, in the word recognition test, the left parietal old/new effect showed a positive deflection reflective of context congruency between study and test words. Namely, the same speaker condition provided the most positive deflection of all correctly identified old words. In the source recognition test, a right frontal positivity was found for the same speaker condition compared to the different speaker conditions, regardless of response success. Taken together, the results of this study suggest that the benefit of context congruency is reflected behaviorally and in ERP modulations traditionally associated with recognition memory.

  18. Voice congruency facilitates word recognition.

    Science.gov (United States)

    Campeanu, Sandra; Craik, Fergus I M; Alain, Claude

    2013-01-01

    Behavioral studies of spoken word memory have shown that context congruency facilitates both word and source recognition, though the level at which context exerts its influence remains equivocal. We measured event-related potentials (ERPs) while participants performed both types of recognition task with words spoken in four voices. Two voice parameters (i.e., gender and accent) varied between speakers, with the possibility that none, one or two of these parameters was congruent between study and test. Results indicated that reinstating the study voice at test facilitated both word and source recognition, compared to similar or no context congruency at test. Behavioral effects were paralleled by two ERP modulations. First, in the word recognition test, the left parietal old/new effect showed a positive deflection reflective of context congruency between study and test words. Namely, the same speaker condition provided the most positive deflection of all correctly identified old words. In the source recognition test, a right frontal positivity was found for the same speaker condition compared to the different speaker conditions, regardless of response success. Taken together, the results of this study suggest that the benefit of context congruency is reflected behaviorally and in ERP modulations traditionally associated with recognition memory.

  19. Indolealkylamines: biotransformations and potential drug-drug interactions.

    Science.gov (United States)

    Yu, Ai-Ming

    2008-06-01

    Indolealkylamine (IAA) drugs are 5-hydroxytryptamine (5-HT or serotonin) analogs that mainly act on the serotonin system. Some IAAs are clinically utilized for antimigraine therapy, whereas other substances are notable as drugs of abuse. In the clinical evaluation of antimigraine triptan drugs, studies on their biotransformations and pharmacokinetics would facilitate the understanding and prevention of unwanted drug-drug interactions (DDIs). A stable, principal metabolite of an IAA drug of abuse could serve as a useful biomarker in assessing intoxication of the IAA substance. Studies on the metabolism of IAA drugs of abuse including lysergic acid amides, tryptamine derivatives and beta-carbolines are therefore emerging. An important role for polymorphic cytochrome P450 2D6 (CYP2D6) in the metabolism of IAA drugs of abuse has been revealed by recent studies, suggesting that variations in IAA metabolism, pharmaco- or toxicokinetics and dynamics can arise from distinct CYP2D6 status, and CYP2D6 polymorphism may represent an additional risk factor in the use of these IAA drugs. Furthermore, DDIs with IAA agents could occur additively at the pharmaco/toxicokinetic and dynamic levels, leading to severe or even fatal serotonin toxicity. In this review, the metabolism and potential DDIs of these therapeutic and abused IAA drugs are described.

  20. WAr on DrugS

    African Journals Online (AJOL)

    2009-04-12

    Apr 12, 2009 ... ABStrAct. Since drugs became both a public and social issue in Nigeria, fear about both the real and .... drugs as being morally reprehensible, and ..... tice system (see for instance, Shaw, 1995; ..... A cut throat business:.

  1. Absorption/desorption in sprays

    International Nuclear Information System (INIS)

    Naimpally, A.

    1987-01-01

    This survey paper shall seek to present the present state of knowledge concerning absorption and desorption in spray chambers. The first part of the paper presents the theories and formulas for the atomization and break-up of sprays in nozzles. Formulas for the average (sauter-mean) diameters are then presented. For the case of absorption processes, the formulas for the dimensionless mass transfer coefficients is in drops. The total; mass transfer is the total of the transfer in individual drops. For the case of desorption of sparingly soluble gases from liquids in a spray chamber, the mass transfer occurs in the spray just at the point of break-up of the jet. Formulas for the desorption of gases are presented

  2. Bent Electro-Absorption Modulator

    DEFF Research Database (Denmark)

    2002-01-01

    by applying a variable electric or electronmagnetic field. The modulation of the complex refractive index results in a modulation of the refractive index contrast and the absorption coefficient for the waveguide at the frequency of the light. By carefully adjusting the composition of the semiconducting...... components and the applied electric field in relation to the frequency of the modulated radiation, the bending losses (and possibly coupling losses) will provide extinction of light guided by the bent waveguide section. The refractive index contract may be modulated while keeping the absorption coefficient......The present invention relates to a method and a device for modulating optical signals based on modulating bending losses in bend, quantum well semiconductor waveguide sections. The complex refractive index of the optical active semiconducting components of the waveguide section is modulated...

  3. Repeated intravenous doxapram induces phrenic motor facilitation.

    Science.gov (United States)

    Sandhu, M S; Lee, K Z; Gonzalez-Rothi, E J; Fuller, D D

    2013-12-01

    Doxapram is a respiratory stimulant used to treat hypoventilation. Here we investigated whether doxapram could also trigger respiratory neuroplasticity. Specifically, we hypothesized that intermittent delivery of doxapram at low doses would lead to long-lasting increases (i.e., facilitation) of phrenic motor output in anesthetized, vagotomized, and mechanically-ventilated rats. Doxapram was delivered intravenously in a single bolus (2 or 6mg/kg) or as a series of 3 injections (2mg/kg) at 5min intervals. Control groups received pH-matched saline injections (vehicle) or no treatment (anesthesia time control). Doxapram evoked an immediate increase in phrenic output in all groups, but a persistent increase in burst amplitude only occurred after repeated dosing with 2mg/kg. At 60min following the last injection, phrenic burst amplitude was 168±24% of baseline (%BL) in the group receiving 3 injections (Pphrenic response to doxapram (2mg/kg) was reduced by 68% suggesting that at low doses the drug was acting primarily via the carotid chemoreceptors. We conclude that intermittent application of doxapram can trigger phrenic neuroplasticity, and this approach might be of use in the context of respiratory rehabilitation following neurologic injury. © 2013.

  4. Microcontainers - an oral drug delivery system for poorly soluble drugs

    DEFF Research Database (Denmark)

    Nielsen, Line Hagner; Petersen, Ritika Singh; Marizza, Paolo

    In oral delivery, it can sometimes be necessary to employ drug delivery systems to achieve targeted delivery to the intestine. Microcontainers are polymeric, cylindrical devices in the micrometer size range (Figure 1), and are suggested as a promising oral drug delivery system [1],[2]. The purpose...... of these studies was to fabricate microcontainers in either SU-8 or biodegradable poly-L-lactic acid (PLLA), and fill the microcontainers with poorly soluble drugs. Furthermore, the application of the microcontainers as an oral drug delivery system was investigated in terms of release, in situ intestinal perfusion...... medium at pH 6.5 was observed. In situ intestinal perfusions were performed in rats of the Eudragit-coated ASSF-filled microcontainers and compared to a furosemide solution. At the end of the study, the small intestine was harvested from the rat and imaged under a light microscope. The absorption rate...

  5. Geometrical interpretation of optical absorption

    Energy Technology Data Exchange (ETDEWEB)

    Monzon, J. J.; Barriuso, A. G.; Sanchez-Soto, L. L. [Departamento de Optica, Facultad de Fisica, Universidad Complutense, E-28040 Madrid (Spain); Montesinos-Amilibia, J. M. [Departamento de Geometria y Topologia, Facultad de Matematicas, Universidad Complutense, E-28040 Madrid (Spain)

    2011-08-15

    We reinterpret the transfer matrix for an absorbing system in very simple geometrical terms. In appropriate variables, the system appears as performing a Lorentz transformation in a (1 + 3)-dimensional space. Using homogeneous coordinates, we map that action on the unit sphere, which is at the realm of the Klein model of hyperbolic geometry. The effects of absorption appear then as a loxodromic transformation, that is, a rhumb line crossing all the meridians at the same angle.

  6. Modernization of Atomic Absorption Spectrophotometer

    International Nuclear Information System (INIS)

    Tasic, Visa; Milivojevic, Dragan; Karabasevic, Dejan

    2003-01-01

    In Copper Institute in Bor, connection has been made between absorption spectrophotometer and standard PC with the aim to make its operation more reliable and comfortable. Applied solution includes both software and hardware components. An I/O interface module has been installed in PC [1]. Software component consists of programs for measuring and interpretation of results. Paper presents details of this job realization.(Author)

  7. Turbulent effective absorptivity and refractivity

    International Nuclear Information System (INIS)

    Rax, J.M.

    1984-09-01

    The problem of wave propagation in a turbulent magnetized plasma is investigated. Considering small scale, low frequency density fluctuations we solve the Maxwell equations and show that the eikonal approximation remains valid with an effective refractivity and an effective absorptivity taking into account the energy diffusion due to the turbulent motion. Then the result is applied to the problem of lower hybrid waves scattering by drift waves density fluctuations in tokamaks

  8. Facilitating Shared Understandings of Risk

    DEFF Research Database (Denmark)

    Mitchell, Robb

    This thesis contributes an identification of a key mechanism and its constituent qualities, for facilitating shared understandings of risk. Globalisation and the pace of technological change increases the uncertainties of decision making within many design and innovation practices. Accordingly......, the focus of participatory workshops has expanded towards addressing broader questions of strategy, business models and other organizational and inter-organisational issues. To develop effective partnerships across the boundaries separating companies, I argue that is necessary for those involved to gain...... or proxy for absent others, 4) an incomplete comic with which children could contribute sketched ideas to a design process 5) a table top tool kits for discussing business relationship issues and 5) a number of bespoke interactive sculpture-like artifacts for provoking insights concerning business dilemmas...

  9. Anterior ethmoid anatomy facilitates dacryocystorhinostomy.

    Science.gov (United States)

    Blaylock, W K; Moore, C A; Linberg, J V

    1990-12-01

    The ethmoid air cell labyrinth lies adjacent to the medial orbital wall, extending even beyond the sutures of the ethmoid bone. Its anatomic relationship to the lacrimal sac fossa is important in lacrimal surgery. We evaluated computed tomographic scans of 190 orbits with normal ethmoid anatomy to define the anatomic relationship of anterior ethmoid air cells to the lacrimal sac fossa. In 93% of the orbits, the cells extended anterior to the posterior lacrimal crest, with 40% entering the frontal process of the maxilla. This anatomic relationship may be used to facilitate the osteotomy during dacryocystorhinostomy. During a 10-year period (310 cases), one of us routinely entered the anterior ethmoid air cells to initiate the osteotomy during dacryocystorhinostomy. This technique has helped to avoid lacerations of the nasal mucosa.

  10. Facilitating Value Co-Creation

    DEFF Research Database (Denmark)

    Veith, Anne; Assaf, Albert; Josiassen, Alexander

    2013-01-01

    will also lead to a high rewards. According to postmodern consumerism theory, consumers are intrinsically motivated to participate (Arnould et al., 2006; Borghini & Caru, 2008; Etgar, 2008; Fisher & Smith, 2011), but may also be extrinsic motivated by, for instance, appraisal and 'autonomy' (Etgar, 2008......). Therefore, for instance, being part of the process is a key incentive for consumers. Postmodern consumers' search for unique experiences calls for individualization, personalization, etc. Although Prahalad & Ramaswamy (2004), Karpen et al. (2008), and Karpen et al. (2011) have presented S-D Logic...... as a middle range theory it is still difficult for organizations to operationalize their co-creation efforts. This paper argues that postmodern consumerism can be used to guide the operationalization of the co-creation process by identifying the key facilitators of co-creation for the postmodern consumer...

  11. Profiling biopharmaceutical deciding properties of absorption of lansoprazole enteric-coated tablets using gastrointestinal simulation technology.

    Science.gov (United States)

    Wu, Chunnuan; Sun, Le; Sun, Jin; Yang, Yajun; Ren, Congcong; Ai, Xiaoyu; Lian, He; He, Zhonggui

    2013-09-10

    The aim of the present study was to correlate in vitro properties of drug formulation to its in vivo performance, and to elucidate the deciding properties of oral absorption. Gastrointestinal simulation technology (GST) was used to simulate the in vivo plasma concentration-time curve and was implemented by GastroPlus™ software. Lansoprazole, a typical BCS class II drug, was chosen as a model drug. Firstly, physicochemical and pharmacokinetic parameters of lansoprazole were determined or collected from literature to construct the model. Validation of the developed model was performed by comparison of the predicted and the experimental plasma concentration data. We found that the predicted curve was in a good agreement with the experimental data. Then, parameter sensitivity analysis (PSA) was performed to find the key parameters of oral absorption. The absorption was particularly sensitive to dose, solubility and particle size for lansoprazole enteric-coated tablets. With a single dose of 30 mg and the solubility of 0.04 mg/ml, the absorption was complete. A good absorption could be achieved with lansoprazole particle radius down to about 25 μm. In summary, GST is a useful tool for profiling biopharmaceutical deciding properties of absorption of lansoprazole enteric-coated tablets and guiding the formulation optimization. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  12. Prediction of Human Intestinal Absorption of Compounds Using Artificial Intelligence Techniques.

    Science.gov (United States)

    Kumar, Rajnish; Sharma, Anju; Siddiqui, Mohammed Haris; Tiwari, Rajesh Kumar

    2017-01-01

    Information about Pharmacokinetics of compounds is an essential component of drug design and development. Modeling the pharmacokinetic properties require identification of the factors effecting absorption, distribution, metabolism and excretion of compounds. There have been continuous attempts in the prediction of intestinal absorption of compounds using various Artificial intelligence methods in the effort to reduce the attrition rate of drug candidates entering to preclinical and clinical trials. Currently, there are large numbers of individual predictive models available for absorption using machine learning approaches. Six Artificial intelligence methods namely, Support vector machine, k- nearest neighbor, Probabilistic neural network, Artificial neural network, Partial least square and Linear discriminant analysis were used for prediction of absorption of compounds. Prediction accuracy of Support vector machine, k- nearest neighbor, Probabilistic neural network, Artificial neural network, Partial least square and Linear discriminant analysis for prediction of intestinal absorption of compounds was found to be 91.54%, 88.33%, 84.30%, 86.51%, 79.07% and 80.08% respectively. Comparative analysis of all the six prediction models suggested that Support vector machine with Radial basis function based kernel is comparatively better for binary classification of compounds using human intestinal absorption and may be useful at preliminary stages of drug design and development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Radiotracer investigation of the cold-vapour atomic absorption method of analysis for trace mercury

    International Nuclear Information System (INIS)

    Stuart, D.C.

    1978-01-01

    Because of certain problems found in application of the atomic absorption method for trace analysis of mercury, a careful check of the procedures used was undertaken, with radiotracer mercury to facilitate the investigation. The results obtained, in conjunction with those of sample ashing procedures, indicate that the method is less straightforward than its simplicity suggests. (Auth.)

  14. Enriching Absorptive Capacity through Social Interaction

    NARCIS (Netherlands)

    Hotho, Jasper J.; Becker-Ritterspach, Florian; Saka-Helmhout, Ayse

    Absorptive capacity is frequently highlighted as a key determinant of knowledge transfer within multinational enterprises. But how individual behaviour translates into absorptive capacity at the subsidiary level, and how this is contingent on subsidiaries' social context, remains under-addressed.

  15. Hopping absorption edge in silicon inversion layers

    International Nuclear Information System (INIS)

    Kostadinov, I.Z.

    1983-09-01

    The low frequency gap observed in the absorption spectrum of silicon inversion layers is related to the AC variable range hopping. The frequency dependence of the absorption coefficient is calculated. (author)

  16. In Vivo Dissolution and Systemic Absorption of Immediate Release Ibuprofen in Human Gastrointestinal Tract under Fed and Fasted Conditions.

    Science.gov (United States)

    Koenigsknecht, Mark J; Baker, Jason R; Wen, Bo; Frances, Ann; Zhang, Huixia; Yu, Alex; Zhao, Ting; Tsume, Yasuhiro; Pai, Manjunath P; Bleske, Barry E; Zhang, Xinyuan; Lionberger, Robert; Lee, Allen; Amidon, Gordon L; Hasler, William L; Sun, Duxin

    2017-12-04

    In vivo drug dissolution in the gastrointestinal (GI) tract is largely unmeasured. The purpose of this clinical study was to evaluate the in vivo drug dissolution and systemic absorption of the BCS class IIa drug ibuprofen under fed and fasted conditions by direct sampling of stomach and small intestinal luminal content. Expanding current knowledge of drug dissolution in vivo will help to establish physiologically relevant in vitro models predictive of drug dissolution. A multilumen GI catheter was orally inserted into the GI tract of healthy human subjects. Subjects received a single oral dose of ibuprofen (800 mg tablet) with 250 mL of water under fasting and fed conditions. The GI catheter facilitated collection of GI fluid from the stomach, duodenum, and jejunum. Ibuprofen concentration in GI fluid supernatant and plasma was determined by LC-MS/MS. A total of 23 subjects completed the study, with 11 subjects returning for an additional study visit (a total of 34 completed study visits). The subjects were primarily white (61%) and male (65%) with an average age of 30 years. The subjects had a median [min, max] weight of 79 [52, 123] kg and body mass index of 25.7 [19.4, 37.7] kg/m 2 . Ibuprofen plasma levels were higher under fasted conditions and remained detectable for 28 h under both conditions. The AUC 0-24 and C max were lower in fed subjects vs fasted subjects, and T max was delayed in fed subjects vs fasted subjects. Ibuprofen was detected immediately after ingestion in the stomach under fasting and fed conditions until 7 h after dosing. Higher levels of ibuprofen were detected in the small intestine soon after dosing in fasted subjects compared to fed. In contrast to plasma drug concentration, overall gastric concentrations remained higher under fed conditions due to increased gastric pH vs fasting condition. The gastric pH increased to near neutrality after feedingbefore decreasing to acidic levels after 7 h. Induction of the fed state reduced systemic

  17. Self-Nanoemulsifying Drug Delivery Systems Based on Melon Oil ...

    African Journals Online (AJOL)

    Erah

    Tropical Journal of Pharmaceutical Research June 2011; 10 (3): 299-307 ... membrane (the major pathway for absorption of drugs) ... [7,8] and a more reproducible plasma level - ... Proximate analysis ..... ionic surfactant-vegetable oil mixture.

  18. Mathematical models for drug diffusion through the compartments of ...

    African Journals Online (AJOL)

    M.A. Khanday

    2016-07-26

    Jul 26, 2016 ... partments have both favourable and adverse effects on human body. The researchers ... absorption, distribution and elimination process of the drug within the body ... models can be used to understand the transport processes.

  19. Evolution of absorption machines; Evolution des machines a absorption

    Energy Technology Data Exchange (ETDEWEB)

    Soide, I; Klemsdal, E [Gaz de France (GDF), 75 - Paris (France); Le Goff, P; Hornut, J M [LSGC-ENSIC, 54 - Nancy (France)

    1998-12-31

    Most of todays absorption air-conditioning machineries use the lithium bromide-water pair. The most performing can operate at a 150-160 deg. C, the temperature being limited by the corrosion resistance of metals with respect to LiBr solutions. Also, there is a revival of interest for water-ammonia systems. These systems require the use of a rectification column which reduces the coefficient of performance. Higher thermal performances are reached with hydrocarbon pairs and ternary mixtures (water-methanol-LiBr etc..). This paper presents different schemes of refrigerating heat pumps based on these different systems. (J.S.)

  20. Evolution of absorption machines; Evolution des machines a absorption

    Energy Technology Data Exchange (ETDEWEB)

    Soide, I.; Klemsdal, E. [Gaz de France (GDF), 75 - Paris (France); Le Goff, P.; Hornut, J.M. [LSGC-ENSIC, 54 - Nancy (France)

    1997-12-31

    Most of todays absorption air-conditioning machineries use the lithium bromide-water pair. The most performing can operate at a 150-160 deg. C, the temperature being limited by the corrosion resistance of metals with respect to LiBr solutions. Also, there is a revival of interest for water-ammonia systems. These systems require the use of a rectification column which reduces the coefficient of performance. Higher thermal performances are reached with hydrocarbon pairs and ternary mixtures (water-methanol-LiBr etc..). This paper presents different schemes of refrigerating heat pumps based on these different systems. (J.S.)

  1. Characteristics of water absorption of beans

    OpenAIRE

    上中, 登紀子; 森, 孝夫; 豊沢, 功; Tokiko, Uenaka; Takao, Mori; Isao, Toyosawa

    2001-01-01

    Characteristics of water absorption of soybean, azuki bean and kidney beans (cv. Toramame and Taishokintoki) were investigated. The way of water absorption of soybean was different from that of other beans, because soybeans absorbed water from whole surface of seed coat immediately after the immersion. Azuki beans absorbed extremely slowly water from only strophiole, and then the water absorption in other tissue was induced by a certain amount of water absorption playing a role of trigger. Th...

  2. Fat digestion and absorption in spice-pretreated rats.

    Science.gov (United States)

    Prakash, Usha N S; Srinivasan, Krishnapura

    2012-02-01

    A few common spices are known to stimulate secretion of bile with higher amount of bile acids which play a major role in digestion and absorption of dietary lipids. It would be appropriate to verify if these spices enable efficient digestion and absorption during high-fat intake. In this context, dietary ginger (0.05%), piperine (0.02%), capsaicin (0.015%), and curcumin (0.5%) were examined for their influence on bile secretion, digestive enzymes of pancreas and absorption of dietary fat in high-fat (30%) fed Wistar rats for 8 weeks. These spices enhanced the activity of pancreatic lipase, amylase, trypsin and chymotrypsin by 22-57%, 32-51%, 63-81% and 12-38%, respectively. Dietary intake of spices along with high-fat enhanced fat absorption. These dietary spices increased bile secretion with higher bile acid content. Stimulation of lipid mobilisation from adipose tissue was suggested by the decrease in perirenal adipose tissue weight by dietary capsaicin and piperine. This was also accompanied by prevention of the accumulation of triglyceride in liver and serum in high-fat fed rats. Activities of key lipogenic enzymes in liver were reduced which was accompanied by an increased activity of hormone-sensitive lipase. Thus, dietary ginger and other spice compounds enhance fat digestion and absorption in high-fat fed situation through enhanced secretion of bile salts and a stimulation of the activity pancreatic lipase. At the same time, the energy expenditure is facilitated by these spices to prevent the accumulation of absorbed fat. Copyright © 2011 Society of Chemical Industry.

  3. COPD - control drugs

    Science.gov (United States)

    Chronic obstructive pulmonary disease - control drugs; Bronchodilators - COPD - control drugs; Beta agonist inhaler - COPD - control drugs; Anticholinergic inhaler - COPD - control drugs; Long-acting inhaler - COPD - control drugs; ...

  4. Lactulose stimulates calcium absorption in postmenopausal women

    NARCIS (Netherlands)

    Heuvel, E.G.H.M. van den; Muijs, T.; Dokkum, W. van; Schaafsma, G.

    1999-01-01

    Animal studies have indicated that calcium absorption is increased by lactulose, a synthetic disaccharide. Therefore, the influence of lactulose on calcium absorption was measured in postmenopausal women who may benefit from the possible enhancing effect of lactulose on calcium absorption. Twelve

  5. Uniform semiclassical approximation for absorptive scattering systems

    International Nuclear Information System (INIS)

    Hussein, M.S.; Pato, M.P.

    1987-07-01

    The uniform semiclassical approximation of the elastic scattering amplitude is generalized to absorptive systems. An integral equation is derived which connects the absorption modified amplitude to the absorption free one. Division of the amplitude into a diffractive and refractive components is then made possible. (Author) [pt

  6. Iron absorption in relation to iron status

    International Nuclear Information System (INIS)

    Magnusson, B.; Bjoern-Rasmussen, E.; Hallberg, L.; Rossander, L.

    1981-01-01

    The absorption from a 3 mg dose of ferrous iron was measured in 250 male subjects. The absorption was related to the log concentration of serum ferritin in 186 subjects of whom 99 were regular blood donors (r= -0.76), and to bone marrow haemosiderin grading in 52 subjects with varying iron status. The purpose was to try and establish a percentage absorption from such a dose that is representative of subjects who are borderline iron deficient. This information is necessary for food iron absorption studies in order (1) to calculate the absorption of iron from the diet at a given iron status and (2) compare the absorption of iron from different meals studied in different groups of subjects by different investigarors. The results suggest that an absorption of about 40% of a 3 mg reference dose of ferrous iron is given in a fasting state, roughly corresponds to the absorption in borderline-iron-deficient subjects. The results indicate that this 40% absorption value corresponds to a serum ferritin level of 30 μg/l and that food iron absorption in a group of subjects should be expressed preferably as the absorption corresponding to a reference-dose absorption of 45%, or possibly a serum ferritin level of 30 μg/l. (author)

  7. [Orphan drugs].

    Science.gov (United States)

    Golocorbin Kon, Svetlana; Vojinović, Aleksandra; Lalić-Popović, Mladena; Pavlović, Nebojsa; Mikov, Momir

    2013-01-01

    Drugs used for treatment of rare diseases are known worldwide under the term of orphan drugs because pharmaceutical companies have not been interested in "adopting" them, that is in investing in research, developing and producing these drugs. This kind of policy has been justified by the fact that these drugs are targeted for small markets, that only a small number of patients is available for clinical trials, and that large investments are required for the development of drugs meant to treat diseases whose pathogenesis has not yet been clarified in majority of cases. The aim of this paper is to present previous and present status of orphan drugs in Serbia and other countries. THE BEGINNING OF ORPHAN DRUGS DEVELOPMENT: This problem was first recognized by Congress of the United States of America in January 1983, and when the "Orphan Drug Act" was passed, it was a turning point in the development of orphan drugs. This law provides pharmaceutical companies with a series of reliefs, both financial ones that allow them to regain funds invested into the research and development and regulatory ones. Seven years of marketing exclusivity, as a type of patent monopoly, is the most important relief that enables companies to make large profits. There are no sufficient funds and institutions to give financial support to the patients. It is therefore necessary to make health professionals much more aware of rare diseases in order to avoid time loss in making the right diagnosis and thus to gain more time to treat rare diseases. The importance of discovery, development and production of orphan drugs lies in the number of patients whose life quality can be improved significantly by administration of these drugs as well as in the number of potential survivals resulting from the treatment with these drugs.

  8. Facilitation of decommissioning light water reactors

    International Nuclear Information System (INIS)

    Moore, E.B. Jr.

    1979-12-01

    Information on design features, special equipment, and construction methods useful in the facilitation of decommissioning light water reactors is presented. A wide range of facilitation methods - from improved documentation to special decommissioning tools and techniques - is discussed. In addition, estimates of capital costs, cost savings, and radiation dose reduction associated with these facilitation methods are given

  9. Online interprofessional education facilitation: A scoping review.

    Science.gov (United States)

    Evans, Sherryn Maree; Ward, Catherine; Reeves, Scott

    2018-04-22

    The use of online media to deliver interprofessional education (IPE) is becoming more prevalent across health professions education settings. Facilitation of IPE activities is known to be critical to the effective delivery of IPE, however, specifics about the nature of online IPE facilitation remains unclear. To explore the health professions education literature to understand the extent, range and nature of research on online IPE facilitation. Scoping review methodology was used to guide a search of four electronic databases for relevant papers. Of the 2095 abstracts initially identified, after screening of both abstracts and full-text papers, 10 studies were selected for inclusion in this review. Following abstraction of key information from each study, a thematic analysis was undertaken. Three key themes emerged to describe the nature of the IPE facilitation literature: (1) types of online IPE facilitation contributions, (2) the experience of online IPE facilitation and (3) personal outcomes of online IPE facilitation. These IPE facilitation themes were particularly focused on facilitation of interprofessional student teams on an asynchronous basis. While the included studies provide some insight into the nature of online IPE facilitation, future research is needed to better understand facilitator contributions, and the facilitation experience and associated outcomes, both relating to synchronous and asynchronous online environments.

  10. Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation: Report of an FDA Public Workshop.

    Science.gov (United States)

    Zhang, X; Duan, J; Kesisoglou, F; Novakovic, J; Amidon, G L; Jamei, M; Lukacova, V; Eissing, T; Tsakalozou, E; Zhao, L; Lionberger, R

    2017-08-01

    On May 19, 2016, the US Food and Drug Administration (FDA) hosted a public workshop, entitled "Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation." The topic of mechanistic oral absorption modeling, which is one of the major applications of physiologically based pharmacokinetic (PBPK) modeling and simulation, focuses on predicting oral absorption by mechanistically integrating gastrointestinal transit, dissolution, and permeation processes, incorporating systems, active pharmaceutical ingredient (API), and the drug product information, into a systemic mathematical whole-body framework. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  11. 78 FR 48691 - Food and Drug Administration Patient Network Annual Meeting; Demystifying Food and Drug...

    Science.gov (United States)

    2013-08-09

    ... 240-316-3200 ext. 207. If you need special accommodations due to a disability, please specify those... impact the drug development and review paradigm. Though several programs exist that facilitate patient...

  12. AIDSinfo Drug Database

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content Drugs Home Drugs Find information on FDA-approved HIV/ ... infection drugs and investigational HIV/AIDS drugs. Search Drugs Search drug Search Icon What's this? Close Popup ...

  13. Facilitating Collaboration in Online Groups

    Directory of Open Access Journals (Sweden)

    Geralyn E Stephens

    2017-02-01

    Full Text Available Demonstrating the ability to collaborate effectively is essential for students moving into 21st century workplaces. Employers are expecting new hires to already possess group-work skills and will seek evidence of their ability to cooperate, collaborate, and complete projects with colleagues, including remotely or at a distance. Instructional activities and assignments that provide students with a variety of ways to engage each other have a direct and immediate effect on their academic performance. This paper shares the Facilitating Collaboration in Online Groups (FCOG instructional planning strategy. The strategy is designed for faculty use and familiarizes students with the process and technology necessary to collaborate effectively in online classroom groups. The strategy utilizes proven teaching techniques to maximize student-student and student-content relationships. Each of the four (4 sequential phases in the FCOG instructional planning strategy are discussed: 1 Creating Groups, 2 Establishing Expectations, 3 Communication Tools, and 4 Assignments and Activities. The discussion also contains implementation suggestions as well as examples of instructional assignments and activities that provide students with a variety of ways to collaborate to reach the learning outcomes.

  14. Carbon Dioxide Absorption Heat Pump

    Science.gov (United States)

    Jones, Jack A. (Inventor)

    2002-01-01

    A carbon dioxide absorption heat pump cycle is disclosed using a high pressure stage and a super-critical cooling stage to provide a non-toxic system. Using carbon dioxide gas as the working fluid in the system, the present invention desorbs the CO2 from an absorbent and cools the gas in the super-critical state to deliver heat thereby. The cooled CO2 gas is then expanded thereby providing cooling and is returned to an absorber for further cycling. Strategic use of heat exchangers can increase the efficiency and performance of the system.

  15. Phytases for Improved Iron Absorption

    DEFF Research Database (Denmark)

    Nielsen, Anne Veller Friis; Nyffenegger, Christian; Meyer, Anne S.

    2014-01-01

    Microbial phytases (EC 3.1.3.8) catalyse dephosphorylation of phytic acid, which is the primary storage compound for phosphorous in cereal kernels. The negatively charged phosphates in phytic acid chelate iron (Fe3+) and thus retards iron bioavailability in humans 1. Supplementation of microbial...... phytase can improve iron absorption from cereal-based diets 2. In order for phytase to catalyse iron release in vivo the phytase must be robust to low pH and proteolysis in the gastric ventricle. Our work has compared the robustness of five different microbial phytases, evaluating thermal stability...

  16. Iodine Absorption Cells Purity Testing

    Czech Academy of Sciences Publication Activity Database

    Hrabina, Jan; Zucco, M.; Philippe, Ch.; Pham, Minh Tuan; Holá, Miroslava; Acef, O.; Lazar, Josef; Číp, Ondřej

    2017-01-01

    Roč. 17, č. 1 (2017), s. 1-13, č. článku 17010102. ISSN 1424-8220 R&D Projects: GA ČR GA15-18430S; GA MŠk(CZ) LO1212; GA MŠk ED0017/01/01 Institutional support: RVO:68081731 Keywords : iodine cells * absorption spectroscopy * laser spectroscopy * laser standards * frequency stability Subject RIV: BH - Optics, Masers, Lasers OBOR OECD: Optics (including laser optics and quantum optics) Impact factor: 2.677, year: 2016

  17. Microwave Absorption Characteristics of Tire

    Science.gov (United States)

    Zhang, Yuzhe; Hwang, Jiann-Yang; Peng, Zhiwei; Andriese, Matthew; Li, Bowen; Huang, Xiaodi; Wang, Xinli

    The recycling of waste tires has been a big environmental problem. About 280 million waste tires are produced annually in the United States and more than 2 billion tires are stockpiled, which cause fire hazards and health issues. Tire rubbers are insoluble elastic high polymer materials. They are not biodegradable and may take hundreds of years to decompose in the natural environment. Microwave irradiation can be a thermal processing method for the decomposition of tire rubbers. In this study, the microwave absorption properties of waste tire at various temperatures are characterized to determine the conditions favorable for the microwave heating of waste tires.

  18. Obesity and Pediatric Drug Development.

    Science.gov (United States)

    Vaughns, Janelle D; Conklin, Laurie S; Long, Ying; Zheng, Panli; Faruque, Fahim; Green, Dionna J; van den Anker, John N; Burckart, Gilbert J

    2018-05-01

    There is a lack of dosing guidelines for use in obese children. Moreover, the impact of obesity on drug safety and clinical outcomes is poorly defined. The paucity of information needed for the safe and effective use of drugs in obese patients remains a problem, even after drug approval. To assess the current incorporation of obesity as a covariate in pediatric drug development, the pediatric medical and clinical pharmacology reviews under the Food and Drug Administration (FDA) Amendments Act of 2007 and the FDA Safety and Innovation Act (FDASIA) of 2012 were reviewed for obesity studies. FDA labels were also reviewed for statements addressing obesity in pediatric patients. Forty-five drugs studied in pediatric patients under the FDA Amendments Act were found to have statements and key words in the medical and clinical pharmacology reviews and labels related to obesity. Forty-four products were identified similarly with pediatric studies under FDASIA. Of the 89 product labels identified, none provided dosing information related to obesity. The effect of body mass index on drug pharmacokinetics was mentioned in only 4 labels. We conclude that there is little information presently available to provide guidance related to dosing in obese pediatric patients. Moving forward, regulators, clinicians, and the pharmaceutical industry should consider situations in drug development in which the inclusion of obese patients in pediatric trials is necessary to facilitate the safe and effective use of new drug products in the obese pediatric population. © 2018, The American College of Clinical Pharmacology.

  19. Small Airway Absorption and Microdosimetry of Inhaled Corticosteroid Particles after Deposition.

    Science.gov (United States)

    Longest, P Worth; Hindle, Michael

    2017-10-01

    To predict the cellular-level epithelial absorbed dose from deposited inhaled corticosteroid (ICS) particles in a model of an expanding and contracting small airway segment for different particle forms. A computational fluid dynamics (CFD)-based model of drug dissolution, absorption and clearance occurring in the surface liquid of a representative small airway generation (G13) was developed and used to evaluate epithelial dose for the same deposited drug mass of conventional microparticles, nanoaggregates and a true nanoaerosol. The ICS medications considered were budesonide (BD) and fluticasone propionate (FP). Within G13, total epithelial absorption efficiency (AE) and dose uniformity (microdosimetry) were evaluated. Conventional microparticles resulted in very poor AE of FP (0.37%) and highly nonuniform epithelial absorption, such that <5% of cells received drug. Nanoaggregates improved AE of FP by a factor of 57-fold and improved dose delivery to reach approximately 40% of epithelial cells. True nanoaerosol resulted in near 100% AE for both drugs and more uniform drug delivery to all cells. Current ICS therapies are absorbed by respiratory epithelial cells in a highly nonuniform manner that may partially explain poor clinical performance in the small airways. Both nanoaggregates and nanoaerosols can significantly improve ICS absorption efficiency and uniformity.

  20. Indolealkylamines: Biotransformations and Potential Drug–Drug Interactions

    OpenAIRE

    Yu, Ai-Ming

    2008-01-01

    Indolealkylamine (IAA) drugs are 5-hydroxytryptamine (5-HT or serotonin) analogs that mainly act on the serotonin system. Some IAAs are clinically utilized for antimigraine therapy, whereas other substances are notable as drugs of abuse. In the clinical evaluation of antimigraine triptan drugs, studies on their biotransformations and pharmacokinetics would facilitate the understanding and prevention of unwanted drug–drug interactions (DDIs). A stable, principal metabolite of an IAA drug of ab...

  1. Drug Facts

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    Full Text Available ... Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of Abuse What ... Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800- ...

  2. Drug Facts

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    Full Text Available ... Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? ... Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800-662- ...

  3. Antineoplastic Drugs

    Science.gov (United States)

    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).

  4. Drugged Driving

    Science.gov (United States)

    ... Survey Results Synthetic Cannabinoids (K2/Spice) Unpredictable Danger Drug and Alcohol Use in College-Age Adults in 2016 Monitoring the Future 2016 Survey Results Drug and Alcohol Use in College-Age Adults in 2015 View All NIDA Home ...

  5. Predicting transporter-mediated drug interactions: Commentary on: "Pharmacokinetic evaluation of a drug transporter cocktail consisting of digoxin, furosemide, metformin and rosuvastatin" and "Validation of a microdose probe drug cocktail for clinical drug interaction assessments for drug transporters and CYP3A".

    Science.gov (United States)

    Zhang, L; Sparreboom, A

    2017-04-01

    Transporters, expressed in various tissues, govern the absorption, distribution, metabolism, and excretion of drugs, and consequently their inherent safety and efficacy profiles. Drugs may interact with a transporter as a substrate and/or an inhibitor. Understanding transporter-mediated drug-drug interactions (DDIs), in addition to enzyme-mediated DDIs, is an integral part of risk assessment in drug development and regulatory review because the concomitant use of more than one medication in patients is common. © 2016 ASCPT.

  6. Mechanistic understanding of time-dependent oral absorption based on gastric motor activity in humans.

    Science.gov (United States)

    Higaki, Kazutaka; Choe, Sally Y; Löbenberg, Raimar; Welage, Lynda S; Amidon, Gordon L

    2008-09-01

    The relationship of gastric motor activity and gastric emptying of 0.7 mm caffeine pellets with their absorption was investigated in the fed state in healthy human subjects by simultaneous monitoring of antral motility and plasma concentrations. A kinetic model for gastric emptying-dependent absorption yielded multiple phases of gastric emptying and rate constants (k(g)) with large inter-individual differences and large variability in onset of gastric emptying (50-175 min). The model suggests that 50% of the dose is emptied in 1-2h and over 90% emptied by 3.5h following dosing, in all subjects. The maximum values of k(g) (k(g)(max)) were much greater than those reported for emptying of liquids in the fasted state and were comparable to k(g) values in the late Phase II/III of the migrating motor complex (MMC). The model described the observed irregular absorption rate-time and plasma concentration-time profiles adequately but not in detail. The model was more successful at simulating double-peak phenomena in absorption rate profiles and onset of caffeine absorption. The results suggest that gastric emptying regulates drug absorption of small particles in the fed state. Further, estimates of k(a) derived using the time-dependent absorption model were closer to the intrinsic absorption rate constant for caffeine.

  7. Iodine Absorption Cells Purity Testing

    Directory of Open Access Journals (Sweden)

    Jan Hrabina

    2017-01-01

    Full Text Available This article deals with the evaluation of the chemical purity of iodine-filled absorption cells and the optical frequency references used for the frequency locking of laser standards. We summarize the recent trends and progress in absorption cell technology and we focus on methods for iodine cell purity testing. We compare two independent experimental systems based on the laser-induced fluorescence method, showing an improvement of measurement uncertainty by introducing a compensation system reducing unwanted influences. We show the advantages of this technique, which is relatively simple and does not require extensive hardware equipment. As an alternative to the traditionally used methods we propose an approach of hyperfine transitions’ spectral linewidth measurement. The key characteristic of this method is demonstrated on a set of testing iodine cells. The relationship between laser-induced fluorescence and transition linewidth methods will be presented as well as a summary of the advantages and disadvantages of the proposed technique (in comparison with traditional measurement approaches.

  8. Drugs as instruments: a new framework for non-addictive psychoactive drug use.

    Science.gov (United States)

    Müller, Christian P; Schumann, Gunter

    2011-12-01

    Most people who are regular consumers of psychoactive drugs are not drug addicts, nor will they ever become addicts. In neurobiological theories, non-addictive drug consumption is acknowledged only as a "necessary" prerequisite for addiction, but not as a stable and widespread behavior in its own right. This target article proposes a new neurobiological framework theory for non-addictive psychoactive drug consumption, introducing the concept of "drug instrumentalization." Psychoactive drugs are consumed for their effects on mental states. Humans are able to learn that mental states can be changed on purpose by drugs, in order to facilitate other, non-drug-related behaviors. We discuss specific "instrumentalization goals" and outline neurobiological mechanisms of how major classes of psychoactive drugs change mental states and serve non-drug-related behaviors. We argue that drug instrumentalization behavior may provide a functional adaptation to modern environments based on a historical selection for learning mechanisms that allow the dynamic modification of consummatory behavior. It is assumed that in order to effectively instrumentalize psychoactive drugs, the establishment of and retrieval from a drug memory is required. Here, we propose a new classification of different drug memory subtypes and discuss how they interact during drug instrumentalization learning and retrieval. Understanding the everyday utility and the learning mechanisms of non-addictive psychotropic drug use may help to prevent abuse and the transition to drug addiction in the future.

  9. Radiation absorption, water content and contrast medium impregnation of gallstones

    International Nuclear Information System (INIS)

    Schmitt, W.G.H.

    1982-01-01

    Gallstones extracted by surgery were examined for CT density, which was compared with the X-ray film, floating performance and chemical analysis of the stones. So far, the water content of the biliary concrements - 14% on the average - has not been given much attention. Drying will considerably reduce the density; examination of the dried gallstones yields a false picture of direct ray absorption. Pure cholesterol stones do not float in water, and they show positive values on Hounsfield's scale (+30 - +60). The article discusses the question whether CT is suitable for effecting a better selection of gallstone patients who can be treated by drug therapy. (orig.) [de

  10. Drug repurposing based on drug-drug interaction.

    Science.gov (United States)

    Zhou, Bin; Wang, Rong; Wu, Ping; Kong, De-Xin

    2015-02-01

    Given the high risk and lengthy procedure of traditional drug development, drug repurposing is gaining more and more attention. Although many types of drug information have been used to repurpose drugs, drug-drug interaction data, which imply possible physiological effects or targets of drugs, remain unexploited. In this work, similarity of drug interaction was employed to infer similarity of the physiological effects or targets for the drugs. We collected 10,835 drug-drug interactions concerning 1074 drugs, and for 700 of them, drug similarity scores based on drug interaction profiles were computed and rendered using a drug association network with 589 nodes (drugs) and 2375 edges (drug similarity scores). The 589 drugs were clustered into 98 groups with Markov Clustering Algorithm, most of which were significantly correlated with certain drug functions. This indicates that the network can be used to infer the physiological effects of drugs. Furthermore, we evaluated the ability of this drug association network to predict drug targets. The results show that the method is effective for 317 of 561 drugs that have known targets. Comparison of this method with the structure-based approach shows that they are complementary. In summary, this study demonstrates the feasibility of drug repurposing based on drug-drug interaction data. © 2014 John Wiley & Sons A/S.

  11. [Club drugs].

    Science.gov (United States)

    Guerreiro, Diogo Frasquilho; Carmo, Ana Lisa; da Silva, Joaquim Alves; Navarro, Rita; Góis, Carlos

    2011-01-01

    Club drugs are the following substances: Methylenedioxymethamphetamine (MDMA); Methamphetamine; Lysergic Acid Diethylamide (LSD); Ketamine; Gamma-hydroxybutyrate (GHB) and Flunitrazepam. These substances are mainly used by adolescents and young adults, mostly in recreational settings like dance clubs and rave parties. These drugs have diverse psychotropic effects, are associated with several degrees of toxicity, dependence and long term adverse effects. Some have been used for several decades, while others are relatively recent substances of abuse. They have distinct pharmacodynamic and pharmacokinetic properties, are not easy to detect and, many times, the use of club drugs is under diagnosed. Although the use of these drugs is increasingly common, few health professionals feel comfortable with the diagnosis and treatment. The authors performed a systematic literature review, with the goal of synthesising the existing knowledge about club drugs, namely epidemiology, mechanism of action, detection, adverse reactions and treatment. The purpose of this article is creating in Portuguese language a knowledge data base on club drugs, that health professionals of various specialties can use as a reference when dealing with individual with this kind of drug abuse.

  12. Fertility drugs and ovarian cancer.

    Science.gov (United States)

    Ali, Aus Tariq

    2017-06-20

    The aetiology of ovarian cancer is multifactorial with both endogenous and exogenous risk factors playing an important role. The exact pathogenesis of ovarian cancer is still not well understood, despite the number of hypotheses published. Due to an increase in the number of women using fertility drugs, much attention has been focused on the long-term health effects of such drugs. Although fertility drugs facilitate the ovulation process, it is however associated with a significant increase in hormone concentrations, placing exposed women at increased risk of gynaecological cancer. Many clinical and epidemiological studies have examined the association between fertility drugs and ovarian cancer risk. Results from these studies have been contradictory, as some studies have reported an increased risk of ovarian cancer while others reported no increased risk. Nevertheless, recent studies have shown that women who used fertility drugs and did not conceive had a higher risk of developing ovarian cancer, compared to women who used fertility drugs and conceived and delivered successfully. This review discusses the effect of fertility drugs on the risk of developing ovarian cancer, providing details on four possible scenarios associated with fertility treatment. In addition, the limitations of previous studies and their impact on our understanding of the association between fertility drugs and ovarian cancer also have been highlighted. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Pharmacokinetic Variability of Drugs Used for Prophylactic Treatment of Migraine

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer; Ågesen, Frederik Nybye; Pavbro, Agniezka

    2017-01-01

    In this review, we evaluate the variability in the pharmacokinetics of 11 drugs with established prophylactic effects in migraine to facilitate 'personalized medicine' with these drugs. PubMed was searched for 'single-dose' and 'steady-state' pharmacokinetic studies of these 11 drugs. The maximum...

  14. Phosphorus absorption in drip irrigation

    International Nuclear Information System (INIS)

    Guennelon, R.; Habib, R.

    1979-01-01

    Introducing the use of solute phosphate with drip irrigation may be an unsatisfying practice on account of the very weak mobility of PO 4 anion. Nevertheless P can move down to 30-40 cm depth by following the saturated flux along earth-worms holes or crakes, or by displacement in very narrow structural porosity, even in heavy soils. In this case roots cannot easily absorb PO 4 from soil solution, as soon as the soil is quite saturated. On the other hand, it seems that P absorption occurs very quickly and easily when the implantation of 32 P tagged solution is carried out at the border of zone which is concerned by the irrigation effects [fr

  15. HI Absorption in Merger Remnants

    Science.gov (United States)

    Teng, Stacy H.; Veileux, Sylvain; Baker, Andrew J.

    2012-01-01

    It has been proposed that ultraluminous infrared galaxies (ULIRGs) pass through a luminous starburst phase, followed by a dust-enshrouded AGN phase, and finally evolve into optically bright "naked" quasars once they shed their gas/dust reservoirs through powerful wind events. We present the results of our recent 21- cm HI survey of 21 merger remnants with the Green Bank Telescope. These remnants were selected from the QUEST (Quasar/ULIRG Evolution Study) sample of ULIRGs and PG quasars; our targets are all bolometrically dominated by AGN and sample all phases of the proposed ULIRG -> IR-excess quasar -> optical quasar sequence. We explore whether there is an evolutionary connection between ULIRGs and quasars by looking for the occurrence of HI absorption tracing neutral gas outflows; our results will allow us to identify where along the sequence the majority of a merger's gas reservoir is expelled.

  16. Multistage quantum absorption heat pumps.

    Science.gov (United States)

    Correa, Luis A

    2014-04-01

    It is well known that heat pumps, while being all limited by the same basic thermodynamic laws, may find realization on systems as "small" and "quantum" as a three-level maser. In order to quantitatively assess how the performance of these devices scales with their size, we design generalized N-dimensional ideal heat pumps by merging N-2 elementary three-level stages. We set them to operate in the absorption chiller mode between given hot and cold baths and study their maximum achievable cooling power and the corresponding efficiency as a function of N. While the efficiency at maximum power is roughly size-independent, the power itself slightly increases with the dimension, quickly saturating to a constant. Thus, interestingly, scaling up autonomous quantum heat pumps does not render a significant enhancement beyond the optimal double-stage configuration.

  17. Sound absorption with green materials

    Science.gov (United States)

    Trematerra, Amelia; Lombardi, Ilaria

    2017-07-01

    Green materials are a valid alternative to traditional materials that are by-products of processing oil. At the end of their useful life, green materials can be disposed of without polluting the environment. They are now being used in the construction and automotive industries. While, studies are currently being carried out in the aviation sector on the use of green materials for non-structural components of airplanes. Green materials can be used to improve the acoustic comfort inside buildings as well as mitigate reverberation, echoes effects and reduce the transmission of noise between rooms. In this paper, the acoustic measurements of the properties of green materials are reported. The absorption coefficient of samples of the materials were measured in the frequency range from 200 Hz to 2,000 Hz with an impedance tube, with the flow resistance being measured.

  18. Mixture for plugging absorption zones

    Energy Technology Data Exchange (ETDEWEB)

    Sitinkov, G V; Kovalenko, N G; Makarov, L V; Zinnatulchin, Ts Kh

    1981-01-17

    A mixture is proposed for plugging absorption zones. The mixture contains synthetic polymer and a solvent. So as to increase the penetrability of the mixture through a reduction in its viscosity and an increase in insulation properties, the compound contains either Capron or Neilon as the synthetic polyamide resin polmyer, and concentrated chloride as the solvent. The mixture is prepared in a special AzINMASh-30 unit (acid cart). After the mixture has been produced, it is injected into the borehole by means of an acid cart pump. So as to prevent coaggulation at the point when the mixture in injected into the stratum through tubes, the mixture is placed betwen chemically inert fluids, for example, a clay mortar. The inert and compressed fluids are injected by means of a cementing unit. The entire process of production and application of the mixture is simple and fully automated through the use of well-known equipment.

  19. Characterization of particulate drug delivery systems for oral delivery of Peptide and protein drugs.

    Science.gov (United States)

    Christophersen, Philip Carsten; Fano, Mathias; Saaby, Lasse; Yang, Mingshi; Nielsen, Hanne Mørck; Mu, Huiling

    2015-01-01

    Oral drug delivery is a preferred route because of good patient compliance. However, most peptide/ protein drugs are delivered via parenteral routes because of the absorption barriers in the gastrointestinal (GI) tract such as enzymatic degradation by proteases and low permeability acrossthe biological membranes. To overcome these barriers, different formulation strategies for oral delivery of biomacromolecules have been proposed, including lipid based formulations and polymer-based particulate drug delivery systems (DDS). The aim of this review is to summarize the existing knowledge about oral delivery of peptide/protein drugs and to provide an overview of formulationand characterization strategies. For a better understanding of the challenges in oral delivery of peptide/protein drugs, the composition of GI fluids and the digestion processes of different kinds of excipients in the GI tract are summarized. Additionally, the paper provides an overview of recent studies on characterization of solid drug carriers for peptide/protein drugs, drug distribution in particles, drug release and stability in simulated GI fluids, as well as the absorption of peptide/protein drugs in cell-based models. The use of biorelevant media when applicable can increase the knowledge about the quality of DDS for oral protein delivery. Hopefully, the knowledge provided in this review will aid the establishment of improved biorelevant models capable of forecasting the performance of particulate DDS for oral peptide/protein delivery.

  20. Drug Facts

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    Full Text Available ... MDMA (Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco ... Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You ...

  1. Drug Facts

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    Full Text Available ... Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA ( ... Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/ ...

  2. Drug Facts

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    Full Text Available ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth ( ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine ...

  3. Drug Facts

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    Full Text Available ... Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain ... About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other ...

  4. Drug Metabolism

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 3. Drug Metabolism: A Fascinating Link Between Chemistry and Biology. Nikhil Taxak Prasad V Bharatam. General Article Volume 19 Issue 3 March 2014 pp 259-282 ...

  5. Drugged Driving

    Science.gov (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  6. Club Drugs

    Science.gov (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  7. Drug Metabolism

    Indian Academy of Sciences (India)

    IAS Admin

    behind metabolic reactions, importance, and consequences with several ... required for drug action. ... lism, which is catalyzed by enzymes present in the above-men- ... catalyze the transfer of one atom of oxygen to a substrate produc-.

  8. Drug Facts

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    Full Text Available ... Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and ... Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can ...

  9. Drug Facts

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    Full Text Available ... 800-662-HELP (4357) at any time to find drug treatment centers near you. I want my ... is making positive changes in her life. She finds support from family and friends who don't ...

  10. Drug Facts

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    Full Text Available ... That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, ... Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) ...

  11. Drug Facts

    Medline Plus

    Full Text Available ... Together The Link Between Drug Use and HIV/AIDS Treatment & Recovery Why Does a Person Need Treatment? ... of Health (NIH) , the principal biomedical and behavioral research agency of the United States Government. NIH is ...

  12. Drug Reactions

    Science.gov (United States)

    ... Kids and Teens Pregnancy and Childbirth Women Men Seniors Your Health Resources Healthcare Management End-of-Life Issues Insurance & Bills Self Care Working With Your Doctor Drugs, Procedures & Devices Over-the- ...

  13. Drug Facts

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    Full Text Available ... prescription drugs. The addiction slowly took over his life. I need different people around me. To stop ... marijuana, "Cristina" is making positive changes in her life. She finds support from family and friends who ...

  14. Drug Resistance

    Science.gov (United States)

    ... Drug-resistance testing is also recommended for all pregnant women with HIV before starting HIV medicines and also in some pregnant women already taking HIV medicines. Pregnant women will work with their health ...

  15. Drug Facts

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    Full Text Available ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine ...

  16. Drug Addiction

    Science.gov (United States)

    ... as hearing colors Impulsive behavior Rapid shifts in emotions Permanent mental changes in perception Rapid heart rate ... Drug use can negatively affect academic performance and motivation to excel in school. Legal issues. Legal problems ...

  17. Drug Facts

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    Full Text Available ... That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana ( ... Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) ...

  18. Ghana - Land Tenure Facilitation Impact Evaluation

    Data.gov (United States)

    Millennium Challenge Corporation — The MCC-supported Land Title Facilitation Activity (LTF) in Ghana was designed to increase investment and productivity by strengthening property rights. In Ghana,...

  19. 50 CFR 17.107 - Facilitating enforcement.

    Science.gov (United States)

    2010-10-01

    ... WILDLIFE AND PLANTS (CONTINUED) ENDANGERED AND THREATENED WILDLIFE AND PLANTS (CONTINUED) Manatee Protection Areas § 17.107 Facilitating enforcement. Water vehicles operating in manatee sanctuary or refuge...

  20. Phytosterol glycosides reduce cholesterol absorption in humans

    OpenAIRE

    Lin, Xiaobo; Ma, Lina; Racette, Susan B.; Anderson Spearie, Catherine L.; Ostlund, Richard E.

    2009-01-01

    Dietary phytosterols inhibit intestinal cholesterol absorption and regulate whole body cholesterol excretion and balance. However, they are biochemically heterogeneous and a portion is glycosylated in some foods with unknown effects on biological activity. We tested the hypothesis that phytosterol glycosides reduce cholesterol absorption in humans. Phytosterol glycosides were extracted and purified from soy lecithin in a novel two-step process. Cholesterol absorption was measured in a series ...

  1. Vitamin B12 absorption from eggs.

    Science.gov (United States)

    Doscherholmen, A; McMahon, J; Ripley, D

    1975-09-01

    The assimilation of 57Co B12 from in vivo labeled eggs was much inferior to that of a comparable amount of crystalline 57Co B12. Furthermore, the absorption varied with the form in which the eggs were served. Judged by the urinary excretion test and the plasma absorption of radioactivity the average absorption from boiled and fried eggs was more than twice that from scrambled whole eggs, but less than half that absorbed from crystalline 57Co B12.

  2. Flame emission, atomic absorption and fluorescence spectrometry

    International Nuclear Information System (INIS)

    Horlick, G.

    1980-01-01

    Six hundred and thirty references are cited in this review. The information in the review is divided into 12 major areas: books, reviews, and bibliographies; fundamental studies in flames; developments in instrumentation; measurement techniques and procedure; flame emission spectrometry; flame atomic absorption spectrometry; flame molecular absorption spectrometry; electrothermal atomization atomic absorption spectroscopy; hydride generation techniques; graphite furnace atomic emission spectrometry; atomic fluorescence spectrometry; and analytical comparisons

  3. The Effect of Soya bean ( Glycine max ) on Pefloxacin Absorption in ...

    African Journals Online (AJOL)

    The study was to investigate the effect of soya bean on the absorption of pefloxacin when given by oral route in rats. The first group of animals feeding on standard pellet feeds was given pefloxacin (8 mg/kg, p.o), while the second and third groups were also given the drug at the same dosage level but were fed with 50 ...

  4. Investigation of clinical pharmacokinetic variability of an opioid antagonist through physiologically based absorption modeling.

    Science.gov (United States)

    Ding, Xuan; He, Minxia; Kulkarni, Rajesh; Patel, Nita; Zhang, Xiaoyu

    2013-08-01

    Identifying the source of inter- and/or intrasubject variability in pharmacokinetics (PK) provides fundamental information in understanding the pharmacokinetics-pharmacodynamics relationship of a drug and project its efficacy and safety in clinical populations. This identification process can be challenging given that a large number of potential causes could lead to PK variability. Here we present an integrated approach of physiologically based absorption modeling to investigate the root cause of unexpectedly high PK variability of a Phase I clinical trial drug. LY2196044 exhibited high intersubject variability in the absorption phase of plasma concentration-time profiles in humans. This could not be explained by in vitro measurements of drug properties and excellent bioavailability with low variability observed in preclinical species. GastroPlus™ modeling suggested that the compound's optimal solubility and permeability characteristics would enable rapid and complete absorption in preclinical species and in humans. However, simulations of human plasma concentration-time profiles indicated that despite sufficient solubility and rapid dissolution of LY2196044 in humans, permeability and/or transit in the gastrointestinal (GI) tract may have been negatively affected. It was concluded that clinical PK variability was potentially due to the drug's antagonism on opioid receptors that affected its transit and absorption in the GI tract. Copyright © 2013 Wiley Periodicals, Inc.

  5. Can lipid nanoparticles improve intestinal absorption?

    Science.gov (United States)

    Mendes, M; Soares, H T; Arnaut, L G; Sousa, J J; Pais, A A C C; Vitorino, C

    2016-12-30

    Lipid nanoparticles and their multiple designs have been considered appealing nanocarrier systems. Bringing the benefits of these nanosystems together with conventional coating technology clearly results in product differentiation. This work aimed at developing an innovative solid dosage form for oral administration based on tableting nanostructured lipid carriers (NLC), coated with conventional polymer agents. NLC dispersions co-encapsulating olanzapine and simvastatin (Combo-NLC) were produced by high pressure homogenization, and evaluated in terms of scalability, drying procedure, tableting and performance from in vitro release, cytotoxicity and intestinal permeability stand points. Factorial design indicated that the scaling-up of the NLC production is clearly feasible. Spray-drying was the method selected to obtain dry particles, not only because it consists of a single step procedure, but also because it facilitates the coating process of NLC with different polymers. Modified NLC formulations with the polymers allowed obtaining distinct release mechanisms, comprising immediate, delayed and prolonged release. Sureteric:Combo-NLC provided a low cytotoxicity profile, along with a ca. 12-fold OL/3-fold SV higher intestinal permeability, compared to those obtained with commercial tablets. Such findings can be ascribed to drug protection and control over release promoted by NLC, supporting them as a versatile platform able to be modified according to the intended needs. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Emission and Absorption Entropy Generation in Semiconductors

    DEFF Research Database (Denmark)

    Reck, Kasper; Varpula, Aapo; Prunnila, Mika

    2013-01-01

    While emission and absorption entropy generation is well known in black bodies, it has not previously been studied in semiconductors, even though semiconductors are widely used for solar light absorption in modern solar cells [1]. We present an analysis of the entropy generation in semiconductor...... materials due to emission and absorption of electromagnetic radiation. It is shown that the emission and absorption entropy generation reduces the fundamental limit on the efficiency of any semiconductor solar cell even further than the Landsberg limit. The results are derived from purely thermodynamical...

  7. X-ray absorption in atomic potassium

    International Nuclear Information System (INIS)

    Gomilsek, Jana Padeznik; Kodre, Alojz; Arcon, Iztok; Nemanic, Vincenc

    2008-01-01

    A new high-temperature absorption cell for potassium vapor is described. X-ray absorption coefficient of atomic potassium is determined in the energy interval of 600 eV above the K edge where thresholds for simultaneous excitations of 1s and outer electrons, down to [1s2p] excitation, appear. The result represents also the atomic absorption background for XAFS (X-ray absorption fine structure) structure analysis. The K ionization energy in the potassium vapor is determined and compared with theoretical data and with the value for the metal

  8. Annette Bunge: developing the principles in percutaneous absorption using chemical engineering principles.

    Science.gov (United States)

    Stinchcomb, A L

    2013-01-01

    Annette Bunge and her research group have had the central theme of mathematically modeling the dermal absorption process. Most of the research focus has been on estimating dermal absorption for the purpose of risk assessment, for exposure scenarios in the environment and in the occupational setting. Her work is the basis for the United States Environmental Protection Agency's estimations for dermal absorption from contaminated water. It is also the basis of the dermal absorption estimates used in determining if chemicals should be assigned a 'skin notation' for potential systemic toxicity following occupational skin exposure. The work is truly translational in that it started with mathematical theory, is validated with preclinical and human experiments, and then is used in guidelines to protect human health. Her valued research has also extended into the topical drug bioavailability and bioequivalence assessment field.

  9. Investigating the correlation between in vivo absorption and in vitro release of fenofibrate from lipid matrix particles in biorelevant medium.

    Science.gov (United States)

    Borkar, Nrupa; Xia, Dengning; Holm, René; Gan, Yong; Müllertz, Anette; Yang, Mingshi; Mu, Huiling

    2014-01-23

    Lipid matrix particles (LMP) may be used as better carriers for poorly water-soluble drugs than liquid lipid carriers because of reduced drug mobilization in the formulations. However, the digestion process of solid lipid particles and their effect on the absorption of poorly water-soluble drugs are not fully understood. This study aimed at investigating the effect of particle size of LMP on drug release in vitro as well as absorption in vivo in order to get a better understanding on the effect of degradation of lipid particles on drug solubilisation and absorption. Fenofibrate, a model poorly water-soluble drug, was incorporated into LMP in this study using probe ultrasound sonication. The resultant LMP were characterised in terms of particle size, size distribution, zeta potential, entrapment efficiency, in vitro lipolysis and in vivo absorption in rat model. LMP of three different particle sizes i.e. approximately 100 nm, 400 nm, and 10 μm (microparticles) were produced with high entrapment efficiencies. The in vitro lipolysis study showed that the recovery of fenofibrate in the aqueous phase for 100 nm and 400 nm LMP was significantly higher (pmicroparticles>control. In summary, the present study demonstrated the particle size dependence of bioavailability of fenofibrate loaded LMP in rat model which correlates well with the in vitro drug release performed in the biorelevant medium. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Advances in buccal drug delivery.

    Science.gov (United States)

    Birudaraj, Raj; Mahalingam, Ravichandran; Li, Xiaoling; Jasti, Bhaskara R

    2005-01-01

    The buccal route offers an attractive alternative for systemic drug delivery of drugs because of better patient compliance, ease of dosage form removal in emergencies, robustness, and good accessibility. Use of buccal mucosa for drug absorption was first attempted by Sobrero in 1847, and since then much research was done to deliver drugs through this route. Today, research is more focused on the development of suitable delivery devices, permeation enhancement, and buccal delivery of drugs that undergo a first-pass effect, such as cardiovascular drugs, analgesics, and peptides. In addition, studies have been conducted on the development of controlled or slow release delivery systems for systemic and local therapy of diseases in the oral cavity. In this review, the anatomy and physiology of buccal mucosa, followed by discussion of recent literature on the buccal permeation enhancement, and pathways of enhancement for various molecules are detailed. In addition, bioadhesion theories from historic perspective and current status are discussed. The various dosage forms on the market and in different stages of development are also reviewed.

  11. Transcutaneous drug delivery by liposomes using fractional laser technology.

    Science.gov (United States)

    Fujimoto, Takahiro; Wang, Jian; Baba, Kazuki; Oki, Yuka; Hiruta, Yuki; Ito, Masayuki; Ito, Shinobu; Kanazawa, Hideko

    2017-07-01

    Transdermal delivery of hydrophilic peptides remains a challenge due to their poor cellular uptake and transdermal penetration. We hypothesize that combination of a CO 2 fractional laser to enhance percutaneous absorption and liposomes as transdermal carriers would improve skin penetration of hydrophilic drugs. NA. Liposomes were prepared using membrane fusion lipid dioleoylphosphatidylethanolamine, and used to deliver 5-carboxyfluorescein (CF) and fluorescein isothiocyanate-conjugated ovalbumin (OVA-FITC) as model hydrophilic peptide drugs. Liposome size was estimated by dynamic light scattering. Liposome uptake into murine macrophage cells and penetration or permeation into Yucatan micropig skin after irradiation by CO 2 fractional laser at varying energy levels (laser power and exposure duration) were investigated using Franz cell and fluorescence microscopy. Oxidative damage to the irradiated mouse skin was assessed by electron spin resonance. Size of CF and OVA-FITC encapsulated liposomes was 324 ± 75 nm. Cellular uptake of OVA-FITC delivered by liposomes was 10-fold higher (1,370 relative fluorescence units, RFU) than delivered in solution form (130 RFU). Fractional laser irradiation increased skin permeation rate of CF liposomes (0-10%) and OVA-FITC liposomes (4-40%) in a dose-dependent manner. Although peeling off the stratum corneum facilitated CF liposome penetration at low energy levels (2.69-3.29 J/cm 2 ; 10-20 W for 500 μs), drug permeation was similar (7-8%) in peeled or untreated skin at higher laser energy levels (6.06 J/cm 2 ; 20 W for 1,500 μs). FITC penetrated deeper in the skin after laser irradiation. However, OH, O2-, and VC reactive oxygen species were generated upon irradiation of the skin with a fractional CO 2 laser. Increasing laser power and irradiation, time increased liposome uptake by cells and penetration of peptide drugs across the skin in a dose-dependent manner. High-energy CO 2 fractional laser overcomes the

  12. Drug-drug interactions of antifungal agents and implications for patient care.

    Science.gov (United States)

    Gubbins, Paul O; Amsden, Jarrett R

    2005-10-01

    Drug interactions in the gastrointestinal tract, liver and kidneys result from alterations in pH, ionic complexation, and interference with membrane transport proteins and enzymatic processes involved in intestinal absorption, enteric and hepatic metabolism, renal filtration and excretion. Azole antifungals can be involved in drug interactions at all the sites, by one or more of the above mechanisms. Consequently, azoles interact with a vast array of compounds. Drug-drug interactions associated with amphotericin B formulations are predictable and result from the renal toxicity and electrolyte disturbances associated with these compounds. The echinocandins are unknown cytochrome P450 substrates and to date are relatively devoid of significant drug-drug interactions. This article reviews drug interactions involving antifungal agents that affect other agents and implications for patient care are highlighted.

  13. Promises of Machine Learning Approaches in Prediction of Absorption of Compounds.

    Science.gov (United States)

    Kumar, Rajnish; Sharma, Anju; Siddiqui, Mohammed Haris; Tiwari, Rajesh Kumar

    2018-01-01

    The Machine Learning (ML) is one of the fastest developing techniques in the prediction and evaluation of important pharmacokinetic properties such as absorption, distribution, metabolism and excretion. The availability of a large number of robust validation techniques for prediction models devoted to pharmacokinetics has significantly enhanced the trust and authenticity in ML approaches. There is a series of prediction models generated and used for rapid screening of compounds on the basis of absorption in last one decade. Prediction of absorption of compounds using ML models has great potential across the pharmaceutical industry as a non-animal alternative to predict absorption. However, these prediction models still have to go far ahead to develop the confidence similar to conventional experimental methods for estimation of drug absorption. Some of the general concerns are selection of appropriate ML methods and validation techniques in addition to selecting relevant descriptors and authentic data sets for the generation of prediction models. The current review explores published models of ML for the prediction of absorption using physicochemical properties as descriptors and their important conclusions. In addition, some critical challenges in acceptance of ML models for absorption are also discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Teachers as Friendship Facilitators: Respeto and Personalismo.

    Science.gov (United States)

    Turnbull, Ann P.; Pereira, Lourdes; Blue-Banning, Martha

    2000-01-01

    This article highlights three teachers who were actively involved as friendship facilitators by illuminating their use of a friendship-facilitator framework with three students with moderate/severe disabilities. The framework includes three strategies: finding opportunities to bring children and youth together, acknowledging individual strengths…

  15. Toward Facilitative Mentoring and Catalytic Interventions

    Science.gov (United States)

    Smith, Melissa K.; Lewis, Marilyn

    2015-01-01

    In TESOL teacher mentoring, giving advice can be conceptualized as a continuum, ranging from directive to facilitative feedback. The goal, over time, is to lead toward the facilitative end of the continuum and specifically to catalytic interventions that encourage self-reflection and autonomous learning. This study begins by examining research on…

  16. Smart Polymers in Nasal Drug Delivery.

    Science.gov (United States)

    Chonkar, Ankita; Nayak, Usha; Udupa, N

    2015-01-01

    Nasal drug delivery has now been recognized as a promising route for drug delivery due to its capability of transporting a drug to systemic circulation and central nervous system. Though nasal mucosa offers improved bioavailability and quick onset of action of the drug, main disadvantage associated with nasal drug delivery is mucocilliary clearance due to which drug particles get cleared from the nose before complete absorption through nasal mucosa. Therefore, mucoadhesive polymeric approach can be successfully used to enhance the retention of the drug on nasal mucosal surface. Here, some of the aspects of the stimuli responsive polymers have been discussed which possess liquid state at the room temperature and in response to nasal temperature, pH and ions present in mucous, can undergo in situ gelation in nasal cavity. In this review, several temperature responsive, pH responsive and ion responsive polymers used in nasal delivery, their gelling mechanisms have been discussed. Smart polymers not only able to enhance the retention of the drug in nasal cavity but also provide controlled release, ease of administration, enhanced permeation of the drug and protection of the drug from mucosal enzymes. Thus smart polymeric approach can be effectively used for nasal delivery of peptide drugs, central nervous system dugs and hormones.

  17. Practical-theological facilitation as skilled helping

    Directory of Open Access Journals (Sweden)

    Elmo Pienaar

    2013-11-01

    Full Text Available The article discussed the idea of skilled helping in relation to what has been put forward as practical theological facilitation. It has been argued that various helping relationships, amongst which the author refers to coaching, facilitation, and therapy has more in common than what differentiates them if epistemology is viewed as a unifying concept. As such the scope of practical theology in terms of the contexts and themes in which it might be involved is said to widen. The public dimension of the organisational context, more so than the congregational context, has been put forward as an important habitus of practical-theological facilitation. The organisational involvement of the practical-theological facilitator in terms of professional-vocational skilled helping takes on an actual role through facilitation and other helping modalities.

  18. Particulate absorption properties in the Red Sea from hyperspectral particulate absorption spectra

    KAUST Repository

    Tiwari, Surya Prakash; Zarokanellos, Nikolaos; Kheireddine, Malika; Shanmugam, Palanisamy; Jones, Burton

    2018-01-01

    This paper aims to describe the variability of particulate absorption properties using a unique hyperspectral dataset collected in the Red Sea as part of the TARA Oceans expedition. The absorption contributions by phytoplankton (aph) and non

  19. In vivo analysis of supersaturation/precipitation/absorption behavior after oral administration of pioglitazone hydrochloride salt; determinant site of oral absorption.

    Science.gov (United States)

    Tanaka, Yusuke; Sugihara, Masahisa; Kawakami, Ayaka; Imai, So; Itou, Takafumi; Murase, Hirokazu; Saiki, Kazunori; Kasaoka, Satoshi; Yoshikawa, Hiroshi

    2017-08-30

    The purpose of this study was to evaluate in vivo supersaturation/precipitation/absorption behavior in the gastrointestinal (GI) tract based on the luminal concentration-time profiles after oral administration of pioglitazone (PG, a highly permeable lipophilic base) and its hydrochloride salt (PG-HCl) to rats. In the in vitro precipitation experiment in the classic closed system, while the supersaturation was stable in the simulated gastric condition, PG drastically precipitated in the simulated intestinal condition, particularly at a higher initial degree of supersaturation. Nonetheless, a drastic and moderate improvement in absorption was observed in vivo at a low and high dose of PG-HCl, respectively. Analysis based on the luminal concentration of PG after oral administration of PG-HCl at a low dose revealed that most of the dissolved PG emptied from the stomach was rapidly absorbed before its precipitation in the duodenum. At a high dose of PG-HCl, PG partly precipitated in the duodenum but was absorbed to some extent. Therefore, the extent of the absorption was mainly dependent on the duodenal precipitation behavior. Furthermore, a higher-than expected absorption after oral administration of PG-HCl from in vitro precipitation study may be due to the absorption process in the small intestine, which suppresses the precipitation by removal of the drug. This study successfully clarify the impact of the absorption process on the supersaturation/precipitation/absorption behavior and key absorption site for a salt formulation of a highly permeable lipophilic base based on the direct observation of in vivo luminal concentration. Our findings may be beneficial in developing an ideal physiologically based pharmacokinetic model and in vitro predictive dissolution tools and/or translating the in silico and in vitro data to the in vivo outcome. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Infrared multiphoton absorption and decomposition

    International Nuclear Information System (INIS)

    Evans, D.K.; McAlpine, R.D.

    1984-01-01

    The discovery of infrared laser induced multiphoton absorption (IRMPA) and decomposition (IRMPD) by Isenor and Richardson in 1971 generated a great deal of interest in these phenomena. This interest was increased with the discovery by Ambartzumian, Letokhov, Ryadbov and Chekalin that isotopically selective IRMPD was possible. One of the first speculations about these phenomena was that it might be possible to excite a particular mode of a molecule with the intense infrared laser beam and cause decomposition or chemical reaction by channels which do not predominate thermally, thus providing new synthetic routes for complex chemicals. The potential applications to isotope separation and novel chemistry stimulated efforts to understand the underlying physics and chemistry of these processes. At ICOMP I, in 1977 and at ICOMP II in 1980, several authors reviewed the current understandings of IRMPA and IRMPD as well as the particular aspect of isotope separation. There continues to be a great deal of effort into understanding IRMPA and IRMPD and we will briefly review some aspects of these efforts with particular emphasis on progress since ICOMP II. 31 references