WorldWideScience

Sample records for drug concentration profiles

  1. Predicting Drug Concentration-Time Profiles in Multiple CNS Compartments Using a Comprehensive Physiologically-Based Pharmacokinetic Model

    NARCIS (Netherlands)

    Yamamoto, Yumi; Välitalo, Pyry A; Huntjens, Dymphy R; Proost, Johannes H; Vermeulen, An; Krauwinkel, Walter; Beukers, Margot W; van den Berg, Dirk-Jan; Hartman, Robin; Wong, Yin Cheong; Danhof, Meindert; van Hasselt, John G C; de Lange, Elizabeth C M

    2017-01-01

    Drug development targeting the central nervous system (CNS) is challenging due to poor predictability of drug concentrations in various CNS compartments. We developed a generic physiologically based pharmacokinetic (PBPK) model for prediction of drug concentrations in physiologically relevant CNS

  2. Prescription Drug Profiles PUF

    Data.gov (United States)

    U.S. Department of Health & Human Services — This release contains the Prescription Drug Profiles Public Use Files (PUFs) drawn from Medicare prescription drug claims for the year of the date on which the...

  3. Concentration profiling in rat tissue by high-resolution magic-angle spinning NMR spectroscopy: investigation of a model drug.

    Science.gov (United States)

    Lucas, Laura H; Wilson, Sarah F; Lunte, Craig E; Larive, Cynthia K

    2005-05-01

    The utility of high-resolution magic-angle spinning (HR-MAS) NMR for studying drug delivery in whole tissues was explored by dosing female Sprague-Dawley rats with topical or injectable benzoic acid (BA). In principle, HR-MAS NMR permits the detection of both intra- and extracellular compounds. This is an advantage over the previous detection of topically applied BA using microdialysis coupled to HPLC/UV as microdialysis samples only the extracellular space. Skin and muscle samples were analyzed by (1)H HR-MAS NMR, and BA levels were determined using an external standard solution added to the sample rotor. One to two percent of the BA topical dose was detected in the muscle, showing that BA penetrated through the dermal and subcutaneous layers. Since BA was not detected in the muscle in the microdialysis studies, the NMR spectra revealed the intracellular localization of BA. The amount of BA detected in muscle after subcutaneous injection correlated with the distance from the dosing site. Overall, the results suggest that HR-MAS NMR can distinguish differences in the local concentration of BA varying with tissue type, dosage method, and tissue proximity to the dosing site. The results illustrate the potential of this technique for quantitative analysis of drug delivery and distribution and the challenges to be addressed as the method is refined.

  4. Concentration profiles near an activated enzyme.

    Science.gov (United States)

    Park, Soohyung; Agmon, Noam

    2008-09-25

    When a resting enzyme is activated, substrate concentration profile evolves in its vicinity, ultimately tending to steady state. We use modern theories for many-body effects on diffusion-influenced reactions to derive approximate analytical expressions for the steady-state profile and the Laplace transform of the transient concentration profiles. These show excellent agreement with accurate many-particle Brownian-dynamics simulations for the Michaelis-Menten kinetics. The steady-state profile has a hyperbolic dependence on the distance of the substrate from the enzyme, albeit with a prefactor containing the complexity of the many-body effects. These are most conspicuous for the substrate concentration at the surface of the enzyme. It shows an interesting transition as a function of the enzyme turnover rate. When it is high, the contact concentration decays monotonically to steady state. However, for slow turnover it is nonmonotonic, showing a minimum due to reversible substrate binding, then a maximum due to diffusion of new substrate toward the enzyme, and finally decay to steady state. Under certain conditions one can obtain a good estimate for the critical value of the turnover rate constant at the transition.

  5. [Health and drug consumption profile in Cameroon].

    Science.gov (United States)

    Commeyras, Christophe; Ndo, Jean Rolin; Merabet, Omar; Kone, Hamidou; Rakotondrabe, Faraniaina Patricia

    2006-01-01

    To begin a renewal of national health policy in Cameroon, a steering committee from the Cameroon Ministry of Health and its partners sought to analyze health demand through a national population survey and supply capacity through a national survey of retail drug stores. A survey of healthcare consumers was also conducted. The present publication describes the results of the consumer survey. Their socioeconomic profile of these consumers was much higher than that of the general population. This indicates that the poorest do not use health facilities or even self-medication. Within the population of healthcare consumers, women and children used private for-profit (60 %) and nonprofit (65 %) private health facilities most often, while men used mainly private pharmacies (60 %) and street drug (medication) sellers (62 %). In all, 85 % of the users of formal drug retailers had had a consultation with a healthcare provider. The average consultation cost was 1,440 CFA Francs, but the 7 % who paid the provider directly had an average cost of 1,794 CFA Francs. In all, 22 % did not pay at all, because of free consultations in some health facilities (40 %), personal relationships with prescribers, or other reasons. Hospitalization costs averaged 4,800 CFA Francs, and medical examinations 4,534 CFA Francs. These two categories had the highest percentage of insured patients (12 % and 5 %). Drug costs were 5,067 CFA Francs from pharmacies and 1,308 CFA Francs in the street. Total healthcare costs per person averaged 14,990 CFA Francs. Weighted, drugs accounted for the largest share, followed by hospitalisation, medical examinations, consultations, and transportation. In the formal sector, less than 10 % reported paying fees directly to the healthcare providers rather than to the HF cashier. Except for consultation in the public sector, paying providers was associated with a lower bill. However, 24 % purchased drugs from the healthcare workers, which indicates that drug sales are

  6. Seasonal variation in diurnal atmospheric grass pollen concentration profiles

    DEFF Research Database (Denmark)

    Peel, Robert George; Orby, P.V.; Skjoth, C. A.

    2014-01-01

    In this study, the diurnal atmospheric grass pollen concentration profile within the Danish city of Aarhus was shown to change in a systematic manner as the pollen season progressed. Although diurnal grass pollen profiles can differ greatly from day-to-day, it is common practice to establish...... the time of day when peak concentrations are most likely to occur using seasonally averaged diurnal profiles. Atmospheric pollen loads are highly dependent upon emissions, and different species of grass are known to flower and emit pollen at different times of the day and during different periods...... of the pollen season. Pollen concentrations are also influenced by meteorological factors - directly through those parameters that govern pollen dispersion and transport, and indirectly through the weather-driven flowering process. We found that three different profiles dominated the grass pollen season...

  7. Profiling evolutionary landscapes underlying drug resistance

    DEFF Research Database (Denmark)

    Hickman, Rachel

    bacterial communities i.e. biofilms or dormant metabolic states. Antibiotic drugs are currently our best medicine to treat (against) bacterial pathogens due to antibiotics unique properties of being small molecules that are soluble and act systemically. These qualities allow for many modern medical......, the work involved in this PhD thesis, examines the evolution of antibiotic resistance in bacterial populations. Two main studies were performed: the first to elucidate the molecular mechanisms of collateral sensitive drug pairs and collateral resistance drug pairs in adaptation of Escherichia coli...

  8. Using Potentiometric Free Drug Sensors to Determine the Free Concentration of Ionizable Drugs in Colloidal Systems

    DEFF Research Database (Denmark)

    Tran, Thuy; Chakraborty, Anjan; Xi, Xi

    2018-01-01

    The present study investigates the use of free drug sensors (FDS) to measure free ionized drug concentrations in colloidal systems, including micellar solutions, emulsions, and lipid formulations during in vitro lipolysis. Diphenhydramine hydrochloride (DPH) and loperamide hydrochloride (LOP) were...... selected as model drugs. Self-diffusion nuclear magnetic resonance studies were performed and confirmed the entrapment of drugs in micelles in Brij 35 and sodium taurodeoxycholate (TDC)/phosphatidylcholine (PC) micellar solutions. The FDS measurements indicated that with a constant level of drug...

  9. Case Studies: Profiles of Women Recovering from Drug Addiction.

    Science.gov (United States)

    Miller, Suzanne M.

    1995-01-01

    Profiles two women over an eight-month study who abused alcohol and other drugs while pregnant and describes their recovery from the addiction. Examines, from an ecological framework, the women's experiences with drug addiction, treatment, and recovery, and recounts their situation through each. (JPS)

  10. Validation of predicted exponential concentration profiles of chemicals in soils

    International Nuclear Information System (INIS)

    Hollander, Anne; Baijens, Iris; Ragas, Ad; Huijbregts, Mark; Meent, Dik van de

    2007-01-01

    Multimedia mass balance models assume well-mixed homogeneous compartments. Particularly for soils, this does not correspond to reality, which results in potentially large uncertainties in estimates of transport fluxes from soils. A theoretically expected exponential decrease model of chemical concentrations with depth has been proposed, but hardly tested against empirical data. In this paper, we explored the correspondence between theoretically predicted soil concentration profiles and 84 field measured profiles. In most cases, chemical concentrations in soils appear to decline exponentially with depth, and values for the chemical specific soil penetration depth (d p ) are predicted within one order of magnitude. Over all, the reliability of multimedia models will improve when they account for depth-dependent soil concentrations, so we recommend to take into account the described theoretical exponential decrease model of chemical concentrations with depth in chemical fate studies. In this model the d p -values should estimated be either based on local conditions or on a fixed d p -value, which we recommend to be 10 cm for chemicals with a log K ow > 3. - Multimedia mass model predictions will improve when taking into account depth dependent soil concentrations

  11. Drug problems in contemporary China: a profile of Chinese drug users in a metropolitan area.

    Science.gov (United States)

    Huang, Kaicheng; Zhang, Lening; Liu, Jianhong

    2011-03-01

    Drug problems are reemerging in China since the nation implemented economic reform and an "open door" policy in the early 1980s. This is causing both national and international concern. However, knowledge and understanding of the Chinese drug problem is fairly limited because of the nation's unique social and political history. In response to this shortage of information, our study presents a profile of Chinese drug users. Data were collected from a survey of drug users attending mandatory treatment centres in a large city in 2009. We present a demographic profile of the drug users, describe their patterns of drug use, their access to drugs and their history of drug treatment. Chinese drug users, like those from the U.S., are likely to be unemployed and have a low level of education. However, they are more likely than those in the U.S. to use heroin, Bingdu (methamphetamine) and Maguo (a derivative of methamphetamine), and they pay less for their drugs. This profile of drug users is informative and valuable for drug prevention, intervention, and treatment in the Chinese setting because knowing and understanding the drug population is essential for effective control. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. Human disease-drug network based on genomic expression profiles.

    Science.gov (United States)

    Hu, Guanghui; Agarwal, Pankaj

    2009-08-06

    Drug repositioning offers the possibility of faster development times and reduced risks in drug discovery. With the rapid development of high-throughput technologies and ever-increasing accumulation of whole genome-level datasets, an increasing number of diseases and drugs can be comprehensively characterized by the changes they induce in gene expression, protein, metabolites and phenotypes. We performed a systematic, large-scale analysis of genomic expression profiles of human diseases and drugs to create a disease-drug network. A network of 170,027 significant interactions was extracted from the approximately 24.5 million comparisons between approximately 7,000 publicly available transcriptomic profiles. The network includes 645 disease-disease, 5,008 disease-drug, and 164,374 drug-drug relationships. At least 60% of the disease-disease pairs were in the same disease area as determined by the Medical Subject Headings (MeSH) disease classification tree. The remaining can drive a molecular level nosology by discovering relationships between seemingly unrelated diseases, such as a connection between bipolar disorder and hereditary spastic paraplegia, and a connection between actinic keratosis and cancer. Among the 5,008 disease-drug links, connections with negative scores suggest new indications for existing drugs, such as the use of some antimalaria drugs for Crohn's disease, and a variety of existing drugs for Huntington's disease; while the positive scoring connections can aid in drug side effect identification, such as tamoxifen's undesired carcinogenic property. From the approximately 37K drug-drug relationships, we discover relationships that aid in target and pathway deconvolution, such as 1) KCNMA1 as a potential molecular target of lobeline, and 2) both apoptotic DNA fragmentation and G2/M DNA damage checkpoint regulation as potential pathway targets of daunorubicin. We have automatically generated thousands of disease and drug expression profiles using GEO

  13. Calculation of concentration depth profiles in electron probe microanalysis

    International Nuclear Information System (INIS)

    Andrae, M.

    1996-03-01

    The intention of this thesis is to calculate concentration depth-profiles with Electron Probe Microanalysis. In order to conclude the structure of the sample from the measured intensity of radiation, it is necessary to have an accurate correction procedure. In the first part of the thesis all physical quantities needed for the multiple reflection model are described in detail. There will be more possibilities to compare theoretical predictions with the experiment, if the correction procedure is also valid for tilted specimens. Therefore the model hat to generalize for oblique electron incidence. Several quantities in the multiple reflection model tilted specimens (transmission, coefficient, angular distribution of transmitted electrons most probable angle of transmitted electrons etc.) had to be derived. The possibility extending this model comparatively easily to the analysis of layered specimens is one advantage of this model. The alteration of the important quantities in this case is described. Measurements of some specimens with one layer on a substrate proved that the mean deviation of calculated thicknesses is about 10 %. In order to calculate depth profiles gold and copper were evaporated with Physical Vapour Deposition (PVD) on silver foils. The thicknesses of evaporated films for gold were 50 nm and 100 nm and for copper 65 nm and 130 nm. Then the specimens were annealed with a temperature of approximately 400 degree C. Finally the concentration depth profiles were quantified with Electron Probe Microanalysis. The shape of the profiles was derived from a simple diffusion model valid for the samples under consideration. In order to check the shape of obtained functions a comparison with measurement by Secondary Ion Mass Spectrometry (SIMS) was performed. Errors of calculated, depth profiles resulting from approximations of the multiple reflection model and the unknown mass of diffused substances of the samples, are estimated. (author)

  14. Predicting adverse drug reaction profiles by integrating protein interaction networks with drug structures.

    Science.gov (United States)

    Huang, Liang-Chin; Wu, Xiaogang; Chen, Jake Y

    2013-01-01

    The prediction of adverse drug reactions (ADRs) has become increasingly important, due to the rising concern on serious ADRs that can cause drugs to fail to reach or stay in the market. We proposed a framework for predicting ADR profiles by integrating protein-protein interaction (PPI) networks with drug structures. We compared ADR prediction performances over 18 ADR categories through four feature groups-only drug targets, drug targets with PPI networks, drug structures, and drug targets with PPI networks plus drug structures. The results showed that the integration of PPI networks and drug structures can significantly improve the ADR prediction performance. The median AUC values for the four groups were 0.59, 0.61, 0.65, and 0.70. We used the protein features in the best two models, "Cardiac disorders" (median-AUC: 0.82) and "Psychiatric disorders" (median-AUC: 0.76), to build ADR-specific PPI networks with literature supports. For validation, we examined 30 drugs withdrawn from the U.S. market to see if our approach can predict their ADR profiles and explain why they were withdrawn. Except for three drugs having ADRs in the categories we did not predict, 25 out of 27 withdrawn drugs (92.6%) having severe ADRs were successfully predicted by our approach. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Drug Use Patterns and Socio-Demographic Profiles of Substance ...

    African Journals Online (AJOL)

    Substance abuse is a critical problem in Botswana, yet empirical evidence on substance users is limited. The current study sought to examine patterns of drug use and sociodemographic profiles of clients who sought treatment at a substance abuse treatment centre in Gaborone, Botswana. Findings showed clients' age ...

  16. High Fidelity Drug Repurposing, Molecular Profiling, and Cell Reprogramming

    Science.gov (United States)

    2016-09-01

    the research community and, ultimately, directly to patients. For example, while family history , PSA profile and an abnormal digital rectal exam are...e.g. active surveillance, radical prostatectomy, radiation or hormonal /chemo therapies). CRCs are perfect for medium and high throughput drug

  17. Influence of drug concentration on the diffusion parameters of caffeine

    Science.gov (United States)

    Mustapha, R.Ben; Lafforgue, C.; Fenina, N.; Marty, J.P.

    2011-01-01

    Background and Objectives: In the fields of the pharmaceutical and cosmetic industries and in toxicology, the study of the skin penetration of molecules is very interesting. Various studies have considered the impact of different physicochemical drug characteristics, skin thickness, and formulations, on the transition from the surface of the skin to the underlying tissues or to the systemic circulation; however, the influence of drug concentration on the permeation flux of molecules has rarely been raised. Our study aims to discover the influence of caffeine concentration in a formulation on the percutaneous penetration from gels, as a result of different dose applications to polysulfate membrane and human skin. Materials and Methods: For this purpose, three identical base gels were used at 1, 3, and 5% of caffeine, to evaluate the effect of the concentration of caffeine on in vitro release through the synthetic membrane and ex vivo permeation through the human skin, using diffusion FranzTM cells. Results: The diffusion through the epidermal tissue was significantly slower than through the synthetic membrane, which recorded an increase of flux with an increase in the concentration of caffeine. The skin permeation study showed that diffusion depended not only on the concentration, but also on the deposited amount of gel. Nevertheless, for the same amount of caffeine applied, the flux was more significant from the less concentrated gel. Conclusion: Among all the different concentrations of caffeine examined, 1% gel of caffeine applied at 5 mg / cm2 showed the highest absorption characteristics across human skin. PMID:21572649

  18. Antihypertensive drugs metabolism: an update to pharmacokinetic profiles and computational approaches.

    Science.gov (United States)

    Zisaki, Aikaterini; Miskovic, Ljubisa; Hatzimanikatis, Vassily

    2015-01-01

    Drug discovery and development is a high-risk enterprise that requires significant investments in capital, time and scientific expertise. The studies of xenobiotic metabolism remain as one of the main topics in the research and development of drugs, cosmetics and nutritional supplements. Antihypertensive drugs are used for the treatment of high blood pressure, which is one the most frequent symptoms of the patients that undergo cardiovascular diseases such as myocardial infraction and strokes. In current cardiovascular disease pharmacology, four drug clusters - Angiotensin Converting Enzyme Inhibitors, Beta-Blockers, Calcium Channel Blockers and Diuretics - cover the major therapeutic characteristics of the most antihypertensive drugs. The pharmacokinetic and specifically the metabolic profile of the antihypertensive agents are intensively studied because of the broad inter-individual variability on plasma concentrations and the diversity on the efficacy response especially due to the P450 dependent metabolic status they present. Several computational methods have been developed with the aim to: (i) model and better understand the human drug metabolism; and (ii) enhance the experimental investigation of the metabolism of small xenobiotic molecules. The main predictive tools these methods employ are rule-based approaches, quantitative structure metabolism/activity relationships and docking approaches. This review paper provides detailed metabolic profiles of the major clusters of antihypertensive agents, including their metabolites and their metabolizing enzymes, and it also provides specific information concerning the computational approaches that have been used to predict the metabolic profile of several antihypertensive drugs.

  19. Molecular basis of high viscosity in concentrated antibody solutions: Strategies for high concentration drug product development.

    Science.gov (United States)

    Tomar, Dheeraj S; Kumar, Sandeep; Singh, Satish K; Goswami, Sumit; Li, Li

    2016-01-01

    Effective translation of breakthrough discoveries into innovative products in the clinic requires proactive mitigation or elimination of several drug development challenges. These challenges can vary depending upon the type of drug molecule. In the case of therapeutic antibody candidates, a commonly encountered challenge is high viscosity of the concentrated antibody solutions. Concentration-dependent viscosity behaviors of mAbs and other biologic entities may depend on pairwise and higher-order intermolecular interactions, non-native aggregation, and concentration-dependent fluctuations of various antibody regions. This article reviews our current understanding of molecular origins of viscosity behaviors of antibody solutions. We discuss general strategies and guidelines to select low viscosity candidates or optimize lead candidates for lower viscosity at early drug discovery stages. Moreover, strategies for formulation optimization and excipient design are also presented for candidates already in advanced product development stages. Potential future directions for research in this field are also explored.

  20. Impacts of feeding preweaned calves milk containing drug residues on the functional profile of the fecal microbiota

    OpenAIRE

    Pereira, Richard Van Vleck; Carroll, Laura M.; Lima, Svetlana; Foditsch, Carla; Siler, Julie D.; Bicalho, Rodrigo Carvalho; Warnick, Lorin D.

    2018-01-01

    Feeding drug residue-containing milk to calves is common worldwide and no information is currently available on the impact on the functional profile of the fecal microbiota. Our objective was to characterize the functional profile of the fecal microbiota of preweaned dairy calves fed raw milk with residual concentrations of antimicrobials commonly found in waste milk from birth to weaning. Calves were assigned to a controlled feeding trial being fed milk with no drug residues or milk with ant...

  1. Five-Factor Model personality profiles of drug users

    Directory of Open Access Journals (Sweden)

    Crum Rosa M

    2008-04-01

    Full Text Available Abstract Background Personality traits are considered risk factors for drug use, and, in turn, the psychoactive substances impact individuals' traits. Furthermore, there is increasing interest in developing treatment approaches that match an individual's personality profile. To advance our knowledge of the role of individual differences in drug use, the present study compares the personality profile of tobacco, marijuana, cocaine, and heroin users and non-users using the wide spectrum Five-Factor Model (FFM of personality in a diverse community sample. Method Participants (N = 1,102; mean age = 57 were part of the Epidemiologic Catchment Area (ECA program in Baltimore, MD, USA. The sample was drawn from a community with a wide range of socio-economic conditions. Personality traits were assessed with the Revised NEO Personality Inventory (NEO-PI-R, and psychoactive substance use was assessed with systematic interview. Results Compared to never smokers, current cigarette smokers score lower on Conscientiousness and higher on Neuroticism. Similar, but more extreme, is the profile of cocaine/heroin users, which score very high on Neuroticism, especially Vulnerability, and very low on Conscientiousness, particularly Competence, Achievement-Striving, and Deliberation. By contrast, marijuana users score high on Openness to Experience, average on Neuroticism, but low on Agreeableness and Conscientiousness. Conclusion In addition to confirming high levels of negative affect and impulsive traits, this study highlights the links between drug use and low Conscientiousness. These links provide insight into the etiology of drug use and have implications for public health interventions.

  2. Five-Factor Model personality profiles of drug users.

    Science.gov (United States)

    Terracciano, Antonio; Löckenhoff, Corinna E; Crum, Rosa M; Bienvenu, O Joseph; Costa, Paul T

    2008-04-11

    Personality traits are considered risk factors for drug use, and, in turn, the psychoactive substances impact individuals' traits. Furthermore, there is increasing interest in developing treatment approaches that match an individual's personality profile. To advance our knowledge of the role of individual differences in drug use, the present study compares the personality profile of tobacco, marijuana, cocaine, and heroin users and non-users using the wide spectrum Five-Factor Model (FFM) of personality in a diverse community sample. Participants (N = 1,102; mean age = 57) were part of the Epidemiologic Catchment Area (ECA) program in Baltimore, MD, USA. The sample was drawn from a community with a wide range of socio-economic conditions. Personality traits were assessed with the Revised NEO Personality Inventory (NEO-PI-R), and psychoactive substance use was assessed with systematic interview. Compared to never smokers, current cigarette smokers score lower on Conscientiousness and higher on Neuroticism. Similar, but more extreme, is the profile of cocaine/heroin users, which score very high on Neuroticism, especially Vulnerability, and very low on Conscientiousness, particularly Competence, Achievement-Striving, and Deliberation. By contrast, marijuana users score high on Openness to Experience, average on Neuroticism, but low on Agreeableness and Conscientiousness. In addition to confirming high levels of negative affect and impulsive traits, this study highlights the links between drug use and low Conscientiousness. These links provide insight into the etiology of drug use and have implications for public health interventions.

  3. Serum magnesium concentration in drug-addicted patients.

    Science.gov (United States)

    Karakiewicz, Beata; Kozielec, Tadeusz; Brodowski, Jacek; Chlubek, Dariusz; Noceń, Iwona; Starczewski, Andrzej; Brodowska, Agnieszka; Laszczyńska, Maria

    2007-03-01

    Drug addiction is a complex problem which leads to many somatic, psychic and social diseases. It is accompanied by the disturbed metabolism of various macro and micronutrients. The aim of this study was to assess serum magnesium concentration in drug-addicted patients and analyze whether Human Immunodeficiency Virus (HIV) infection and methadone treatment affect the level of serum magnesium in these patients. The examination was conducted in a group of 83 people - patients of Szczecin-Zdroje Psychiatric Hospital (Poland). They were 21 to 49 years old, and the mean age was 32 +/- 7 years. The control group consisted of 81 healthy individuals. Flame atomic-absorption spectrometry method was used to determine the magnesium concentration. The total serum magnesium concentration was calculated for the whole patient group, subgroups of women and men, a subgroup of people infected with HIV, and a subgroup receiving methadone substitution treatment. How magnesium behaves depending on age and addiction period, was checked. The mean concentration of magnesium in blood serum of the patients examined was 0.57 mmol/L, which was significantly lower than in the control group. In the subgroup of men it was 0.57 mmol/L, and in the subgroup of women - 0.55 mmol/L; the differences were not statistically significant. In the patient group nobody had the appropriate magnesium concentration in blood serum. No significant correlation was found between the magnesium concentration, age of the patients and addiction period. In the subgroup of seropositive people the mean concentration of magnesium was 0.55 mmol/L, and in the subgroup of non-infected patients - 0.58 mmol/L; the difference was not statistically significant. The mean concentration of magnesium in the subgroup treated with methadone was 0.59 mmol/L, and in the subgroup not involved in this type of therapy - 0.55 mmol/L; it was not a statistically significant difference.

  4. Colony Lysate Arrays for Proteomic Profiling of Drug-Tolerant Persisters of Cancer Cell.

    Science.gov (United States)

    Kume, Kohei; Nishizuka, Satoshi S

    2017-09-05

    Functional heterogeneity of cancer cells is one of the key properties to understanding relapse after drug treatment. Hence, clarification is needed with regard to which types of subgroups of cancer cells dominantly contribute to the initiation of relapse. Recently, we established the colony lysate array (CoLA), which is a method that allows comparison of individual colonies at the protein level to assess the initiation of anticancer drug-tolerant persisters (DTPs) based on the reverse-phase protein array (RPPA) system. DTPs grow in various drug concentrations and types showing 2-dimensional growth (∼1 mm) on a flat surface. The size of DTPs are larger than spheroids (∼0.3 mm) in agarose gel, which makes them easy to handle for a number of assays. DTPs provide functional information during the process of their formation, initiating from the origin of a drug-tolerant single cell. Using >2000 DTPs generated from various drugs and doses profiled on the basis of 44 proteins, we demonstrate that the DTPs are clustered on the basis of their proteomic profiles changing in response to drugs and doses. Of interest, nine transcription factors in the DTPs, such as STAT3 and OCT4A, were identified as having decreased or increased levels of proteins in response to gefitinib. Importantly, these results can be obtained only by individual proteomic colony profiling, which may identify alternative therapeutic targets and biomarkers for DTPs that may harbor critical mechanisms for cancer relapse.

  5. Exhaled methane concentration profiles during exercise on an ergometer

    Science.gov (United States)

    Szabó, A; Ruzsanyi, V; Unterkofler, K; Mohácsi, Á; Tuboly, E; Boros, M; Szabó, G; Hinterhuber, H; Amann, A

    2016-01-01

    Exhaled methane concentration measurements are extensively used in medical investigation of certain gastrointestinal conditions. However, the dynamics of endogenous methane release is largely unknown. Breath methane profiles during ergometer tests were measured by means of a photoacoustic spectroscopy based sensor. Five methane-producing volunteers (with exhaled methane level being at least 1 ppm higher than room air) were measured. The experimental protocol consisted of 5 min rest—15 min pedalling (at a workload of 75 W)—5 min rest. In addition, hemodynamic and respiratory parameters were determined and compared to the estimated alveolar methane concentration. The alveolar breath methane level decreased considerably, by a factor of 3–4 within 1.5 min, while the estimated ventilation-perfusion ratio increased by a factor of 2–3. Mean pre-exercise and exercise methane concentrations were 11.4 ppm (SD:7.3) and 2.8 ppm (SD:1.9), respectively. The changes can be described by the high sensitivity of exhaled methane to ventilationperfusion ratio and are in line with the Farhi equation. PMID:25749807

  6. Blood cadmium concentration and lipid profile in Korean adults

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kisok, E-mail: kimkisok@kmu.ac.kr [Department of Public Health, Keimyung University, 1000 Shindang-dong, Daegu 704-701 (Korea, Republic of)

    2012-01-15

    Although animal experiments have shown that cadmium exposure induces alterations in lipid profiles, no epidemiological study of this relationship has been performed. The objective of this study was to evaluate the association between blood cadmium concentration and blood lipid levels in Korean adults. A cross-sectional study comprising participants (n=3903) aged 20 years or older from the 2005, 2008, and 2009 Korea National Health and Nutrition Examination Surveys was conducted. Demographic characteristics and dietary intake were obtained from the participants by questionnaire, and cadmium and lipid levels were determined by analysis of blood samples. After adjusting for demographic and dietary factors, blood concentration of cadmium was positively associated with the risk of low high-density lipoprotein cholesterol (HDL-C) in a dose-dependent manner (p for trend <0.001). In addition, the odds ratios (ORs) of a high triglyceride to HDL-C ratio was significantly increased in the high blood cadmium groups [OR=1.36; 95% confidence interval (CI), 1.03-1.79 for fourth quintile and OR=1.41; 95% CI, 1.07-1.86 for fifth quintile] compared with the lowest quintile group. However, high blood cadmium was not associated with a risk of high total cholesterol, high low-density lipoprotein cholesterol, or high triglycerides. These data suggest that an increased cadmium body burden increases the risk of dyslipidemia, mainly due to the increased risk of low HDL-C and the high ratio of triglycerides to HDL-C.

  7. Skin test concentrations for systemically administered drugs -- an ENDA/EAACI Drug Allergy Interest Group position paper

    DEFF Research Database (Denmark)

    Brockow, K; Garvey, L H; Aberer, W

    2013-01-01

    .We recommend drug concentration for skin testing aiming to achieve a specificity of at least 95%. It has been possible to recommend specific drug concentration for betalactam antibiotics, perioperative drugs, heparins, platinum salts and radiocontrast media. For many other drugs, there is insufficient evidence...... to recommend appropriate drug concentration. There is urgent need for multicentre studies designed to establish and validate drug skin test concentration using standard protocols. For most drugs, sensitivity of skin testing is higher in immediate hypersensitivity compared to nonimmediate hypersensitivity.......Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable...

  8. Cardiovascular Safety Profile of Currently Available Diabetic Drugs

    Science.gov (United States)

    Azimova, Komola; Juan, Zinnia San; Mukherjee, Debabrata

    2014-01-01

    Background Cardiovascular disease is the leading cause of morbidity and mortality among patients with diabetes, underscoring the importance of choosing drugs that do not increase cardiovascular risk and reduce the risk of cardiovascular events. Since 2008, the US Food and Drug Administration has recommended that new drugs for type 2 diabetes undergo clinical trials to demonstrate cardiovascular safety in addition to glycemic benefit. In 2012, the European Medicines Agency issued a similar recommendation. Methods We searched the PubMed, Cochrane CENTRAL, EMBASE, and CINAHL databases from inception through August 2013 and compiled and reviewed the existing data on the cardiovascular safety profiles of currently available diabetic drugs. Results While intensive glycemic control in diabetics has been consistently shown to reduce the risk of microvascular complications, the data on macrovascular risk reduction have not been as clear, and questions have been raised about possible increases in cardiovascular morbidity and mortality. Conclusion Careful selection of drug therapy—paying particular attention to cardiovascular safety—is important in optimizing diabetic therapy. PMID:25598727

  9. Blood cadmium concentration and lipid profile in Korean adults

    International Nuclear Information System (INIS)

    Kim, Kisok

    2012-01-01

    Although animal experiments have shown that cadmium exposure induces alterations in lipid profiles, no epidemiological study of this relationship has been performed. The objective of this study was to evaluate the association between blood cadmium concentration and blood lipid levels in Korean adults. A cross-sectional study comprising participants (n=3903) aged 20 years or older from the 2005, 2008, and 2009 Korea National Health and Nutrition Examination Surveys was conducted. Demographic characteristics and dietary intake were obtained from the participants by questionnaire, and cadmium and lipid levels were determined by analysis of blood samples. After adjusting for demographic and dietary factors, blood concentration of cadmium was positively associated with the risk of low high-density lipoprotein cholesterol (HDL-C) in a dose-dependent manner (p for trend <0.001). In addition, the odds ratios (ORs) of a high triglyceride to HDL-C ratio was significantly increased in the high blood cadmium groups [OR=1.36; 95% confidence interval (CI), 1.03–1.79 for fourth quintile and OR=1.41; 95% CI, 1.07–1.86 for fifth quintile] compared with the lowest quintile group. However, high blood cadmium was not associated with a risk of high total cholesterol, high low-density lipoprotein cholesterol, or high triglycerides. These data suggest that an increased cadmium body burden increases the risk of dyslipidemia, mainly due to the increased risk of low HDL-C and the high ratio of triglycerides to HDL-C.

  10. Zeolite-filled silicone rubber membranes. Experimental determination of concentration profiles

    NARCIS (Netherlands)

    te Hennepe, H.J.C.; Boswerger, W.B.F.; Bargeman, D.; Bargeman, D.; Mulder, M.H.V.; Smolders, C.A.; Smolders, C.A.

    1994-01-01

    Permeant concentrations in silicalite-filled silicone rubber membranes during pervaporation of propanol/water mixtures were measured using multi-layered membranes. Experimentally determined concentration profiles show that the propanol concentration in the silicalite-filled membrane increases with

  11. Profiling online recreational/prescription drugs' customers and overview of drug vending virtual marketplaces.

    Science.gov (United States)

    Orsolini, Laura; Francesconi, Giulia; Papanti, Duccio; Giorgetti, Arianna; Schifano, Fabrizio

    2015-07-01

    Internet and social networking sites play a significant role in the marketing and distribution of recreational/prescription drugs without restrictions. We aimed here at reviewing data relating to the profile of the online drug customer and at describing drug vending websites. The PubMed, Google Scholar, and Scopus databases were searched here in order to elicit data on the socio-demographic characteristics of the recreational marketplaces/online pharmacies' customers and the determinants relating to online drug purchasing activities. Typical online recreational drugs' customers seem to be Caucasian, men, in their 20s, highly educated, and using the web to impact as minimally as possible on their existing work/professional status. Conversely, people without any health insurance seemed to look at the web as a source of more affordable prescription medicines. Drug vending websites are typically presented here with a "no prescription required" approach, together with aggressive marketing strategies. The online availability of recreational/prescriptions drugs remains a public health concern. A more precise understanding of online vending sites' customers may well facilitate the drafting and implementation of proper prevention campaigns aimed at counteracting the increasing levels of online drug acquisition and hence intake activities. Copyright © 2015 John Wiley & Sons, Ltd.

  12. Skin test concentrations for systemically administered drugs -- an ENDA/EAACI Drug Allergy Interest Group position paper.

    Science.gov (United States)

    Brockow, K; Garvey, L H; Aberer, W; Atanaskovic-Markovic, M; Barbaud, A; Bilo, M B; Bircher, A; Blanca, M; Bonadonna, B; Campi, P; Castro, E; Cernadas, J R; Chiriac, A M; Demoly, P; Grosber, M; Gooi, J; Lombardo, C; Mertes, P M; Mosbech, H; Nasser, S; Pagani, M; Ring, J; Romano, A; Scherer, K; Schnyder, B; Testi, S; Torres, M; Trautmann, A; Terreehorst, I

    2013-06-01

    Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable indicator of true hypersensitivity.To promote and standardize reproducible skin testing with safe and nonirritant drug concentrations in the clinical practice, the European Network and European Academy of Allergy and Clinical Immunology (EAACI) Interest Group on Drug Allergy has performed a literature search on skin test drug concentration in MEDLINE and EMBASE, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. Where the literature is poor, we have taken into consideration the collective experience of the group.We recommend drug concentration for skin testing aiming to achieve a specificity of at least 95%. It has been possible to recommend specific drug concentration for betalactam antibiotics, perioperative drugs, heparins, platinum salts and radiocontrast media. For many other drugs, there is insufficient evidence to recommend appropriate drug concentration. There is urgent need for multicentre studies designed to establish and validate drug skin test concentration using standard protocols. For most drugs, sensitivity of skin testing is higher in immediate hypersensitivity compared to nonimmediate hypersensitivity. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Plasma drug concentrations and physiological measures in 'dance party' participants.

    Science.gov (United States)

    Irvine, Rodney J; Keane, Michael; Felgate, Peter; McCann, Una D; Callaghan, Paul D; White, Jason M

    2006-02-01

    The increasing use of (+/-) 3,4-methylenedioxymethamphetamine (MDMA) in the setting of large dance parties ('raves') and clubs has been the source of some concern, because of potential acute adverse events, and because animal studies suggest that MDMA has the potential to damage brain serotonin (5-HT) neurons. However, it is not yet known whether MDMA, as used in the setting of dance parties, leads to plasma levels of MDMA that are associated with toxicity to 5-HT neurons in animals. The present study sought to address this question. Plasma MDMA concentrations, vital signs, and a variety of blood and urine measures were obtained prior to, and hours after, individuals attended a dance party. After the dance party, subjects were without clinical complaints, had measurable amounts of residual MDMA in plasma, and nearly half of the subjects also tested positive for methamphetamine, another amphetamine analog that has been shown to have 5-HT neurotoxic potential in animals. Plasma concentrations of MDMA did not correlate with self-reported use of 'ecstasy' and, in some subjects, overlapped with those that have been associated with 5-HT neurotoxicity in non-human primates. Additional subjects were likely to have had similar concentrations while at the dance party, when one considers the reported time of drug ingestion and the plasma half-life of MDMA in humans. Hematological and biochemical analyses were generally unremarkable. Moderate increases in blood pressure, heart rate and body temperature were observed in the subjects with the highest MDMA plasma concentrations. These findings are consistent with epidemiological findings that most people who use MDMA at dance parties do not develop serious clinical complications, and suggest that some of these individuals may be at risk for developing MDMA-induced toxicity to brain serotonin neurons.

  14. Metabolic profiling using HPLC allows classification of drugs according to their mechanisms of action in HL-1 cardiomyocytes

    International Nuclear Information System (INIS)

    Strigun, Alexander; Wahrheit, Judith; Beckers, Simone; Heinzle, Elmar; Noor, Fozia

    2011-01-01

    Along with hepatotoxicity, cardiotoxic side effects remain one of the major reasons for drug withdrawals and boxed warnings. Prediction methods for cardiotoxicity are insufficient. High content screening comprising of not only electrophysiological characterization but also cellular molecular alterations are expected to improve the cardiotoxicity prediction potential. Metabolomic approaches recently have become an important focus of research in pharmacological testing and prediction. In this study, the culture medium supernatants from HL-1 cardiomyocytes after exposure to drugs from different classes (analgesics, antimetabolites, anthracyclines, antihistamines, channel blockers) were analyzed to determine specific metabolic footprints in response to the tested drugs. Since most drugs influence energy metabolism in cardiac cells, the metabolite 'sub-profile' consisting of glucose, lactate, pyruvate and amino acids was considered. These metabolites were quantified using HPLC in samples after exposure of cells to test compounds of the respective drug groups. The studied drug concentrations were selected from concentration response curves for each drug. The metabolite profiles were randomly split into training/validation and test set; and then analysed using multivariate statistics (principal component analysis and discriminant analysis). Discriminant analysis resulted in clustering of drugs according to their modes of action. After cross validation and cross model validation, the underlying training data were able to predict 50%-80% of conditions to the correct classification group. We show that HPLC based characterisation of known cell culture medium components is sufficient to predict a drug's potential classification according to its mode of action.

  15. Simulation of nitrogen concentration depth profiles in low temperature nitrided stainless steel

    DEFF Research Database (Denmark)

    Christiansen, Thomas; Dahl, Kristian Vinter; Somers, Marcel A. J.

    2006-01-01

    A numerical model is presented, which simulates nitrogen concentration-depth profiles as obtained with low temperature gaseous nitriding of stainless steel. The evolution of the calculated nitrogen concentration-depth profiles is compared with experimental nitriding kinetics. It is shown...

  16. Skin test concentrations for systemically administered drugs -- an ENDA/EAACI Drug Allergy Interest Group position paper

    NARCIS (Netherlands)

    Brockow, K.; Garvey, L. H.; Aberer, W.; Atanaskovic-Markovic, M.; Barbaud, A.; Bilo, M. B.; Bircher, A.; Blanca, M.; Bonadonna, B.; Campi, P.; Castro, E.; Cernadas, J. R.; Chiriac, A. M.; Demoly, P.; Grosber, M.; Gooi, J.; Lombardo, C.; Mertes, P. M.; Mosbech, H.; Nasser, S.; Pagani, M.; Ring, J.; Romano, A.; Scherer, K.; Schnyder, B.; Testi, S.; Torres, M.; Trautmann, A.; Terreehorst, I.

    2013-01-01

    Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable

  17. Evaluation of Postmortem Drug Concentrations in Bile Compared with Blood and Urine in Forensic Autopsy Cases.

    Science.gov (United States)

    Tominaga, Mariko; Michiue, Tomomi; Oritani, Shigeki; Ishikawa, Takaki; Maeda, Hitoshi

    2016-06-01

    For drug screening and pharmaco-/toxicokinetic analysis, bile as a major drug excretion route in addition to urine may be used in forensic autopsy cases; however, there are limited published data on correlations between bile and blood or urine drug concentrations. The present study retrospectively investigated drug concentrations in bile, compared with blood and urine concentrations, reviewing forensic autopsy cases during 6 years (January 2009-December 2014). Drugs were analyzed using automated gas chromatography-mass spectrometry following solid-liquid phase extraction. Compared with peripheral blood concentrations, bile concentrations were higher for most drugs; however, caffeine concentrations were similar. Bile concentrations were mostly lower than urine concentrations for amphetamines, caffeine and methylephedrine, but were usually similar to or higher for other drugs. Significant correlations were detected between bile and peripheral blood concentrations for amphetamines, several cold remedies, phenobarbital, phenothiazine derivatives and diazepam, as well as between bile and urine concentrations for amphetamines, caffeine, diphenhydramine, phenobarbital and promethazine derivatives. These findings suggest that bile can provide supplemental data useful in routine forensic toxicology, for the spectrum of drugs mentioned above, as well as for investigating pharmaco-/toxicokinetics and postmortem redistribution when analyzed in combination with drug concentrations at other sites. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Effect of sodium tripolyphosphate concentration and simulated gastrointestinal fluids on release profile of paracetamol from chitosan microsphere

    Science.gov (United States)

    Mulia, Kamarza; Andrie; Krisanti, Elsa A.

    2018-03-01

    The problem to overcome in oral drug administration is the significant pH changes present in the human digestive system. In this study, ionotropic gelation method employing 2-8% (w/v) tripolyphosphate solutions were used to crosslink chitosan microspheres for a controlled release of paracetamol as a model drug. The release profiles of paracetamol from chitosan microspheres were determined using simulated gastrointestinal fluids having pH values of 1.2, 6.8, and 7.4. The results showed that the paracetamol loading and the encapsulation efficiency values increased with increasing concentration of tripolyphosphate solutions used in the preparation step. Paracetamol released at pH 1.2 and 6.8 buffer solutions was significantly higher than that at pH 7.4; also, more paracetamol was released in the presence of α-amylase and β-glucosidase enzymes. The release profiles showed zero-order release behaviour up to 8 hours where the highest drug release was 39% of the paracetamol loaded in the chitosan microspheres, indicating a strong crosslinking between chitosan and TPP anions. The relatively low accumulated drug release could be compensated by employing suitable enzymes, lower TPP solution concentration, and addition of other biodegradable polymer to reduce the TPP crosslink.

  19. The deconvolution of sputter-etching surface concentration measurements to determine impurity depth profiles

    International Nuclear Information System (INIS)

    Carter, G.; Katardjiev, I.V.; Nobes, M.J.

    1989-01-01

    The quasi-linear partial differential continuity equations that describe the evolution of the depth profiles and surface concentrations of marker atoms in kinematically equivalent systems undergoing sputtering, ion collection and atomic mixing are solved using the method of characteristics. It is shown how atomic mixing probabilities can be deduced from measurements of ion collection depth profiles with increasing ion fluence, and how this information can be used to predict surface concentration evolution. Even with this information, however, it is shown that it is not possible to deconvolute directly the surface concentration measurements to provide initial depth profiles, except when only ion collection and sputtering from the surface layer alone occur. It is demonstrated further that optimal recovery of initial concentration depth profiles could be ensured if the concentration-measuring analytical probe preferentially sampled depths near and at the maximum depth of bombardment-induced perturbations. (author)

  20. Temporal Profiles Dissociate Regional Extracellular Ethanol versus Dopamine Concentrations

    Science.gov (United States)

    2015-01-01

    In vivo monitoring of dopamine via microdialysis has demonstrated that acute, systemic ethanol increases extracellular dopamine in regions innervated by dopaminergic neurons originating in the ventral tegmental area and substantia nigra. Simultaneous measurement of dialysate dopamine and ethanol allows comparison of the time courses of their extracellular concentrations. Early studies demonstrated dissociations between the time courses of brain ethanol concentrations and dopaminergic responses in the nucleus accumbens (NAc) elicited by acute ethanol administration. Both brain ethanol and extracellular dopamine levels peak during the first 5 min following systemic ethanol administration, but the dopamine response returns to baseline while brain ethanol concentrations remain elevated. Post hoc analyses examined ratios of the dopamine response (represented as a percent above baseline) to tissue concentrations of ethanol at different time points within the first 25–30 min in the prefrontal cortex, NAc core and shell, and dorsomedial striatum following a single intravenous infusion of ethanol (1 g/kg). The temporal patterns of these “response ratios” differed across brain regions, possibly due to regional differences in the mechanisms underlying the decline of the dopamine signal associated with acute intravenous ethanol administration and/or to the differential effects of acute ethanol on the properties of subpopulations of midbrain dopamine neurons. This Review draws on neurochemical, physiological, and molecular studies to summarize the effects of acute ethanol administration on dopamine activity in the prefrontal cortex and striatal regions, to explore the potential reasons for the regional differences observed in the decline of ethanol-induced dopamine signals, and to suggest directions for future research. PMID:25537116

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Koenig, Xaver; Kovar, Michael; Rubi, Lena; Mike, Agnes K.; Lukacs, Peter; Gawali, Vaibhavkumar S.; Todt, Hannes [Center for Physiology and Pharmacology, Department of Neurophysiology and -pharmacology, Medical University of Vienna, 1090 Vienna (Austria); Hilber, Karlheinz, E-mail: karlheinz.hilber@meduniwien.ac.at [Center for Physiology and Pharmacology, Department of Neurophysiology and -pharmacology, Medical University of Vienna, 1090 Vienna (Austria); Sandtner, Walter [Center for Physiology and Pharmacology, Institute of Pharmacology, Medical University of Vienna, 1090 Vienna (Austria)

    2013-12-01

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

  3. Impact of active metabolites on monitoring plasma concentrations of therapeutic drugs.

    Science.gov (United States)

    Atkinson, A J; Stec, G P; Lertora, J J; Ruo, T I; Thenot, J P

    1980-01-01

    Monitoring plasma concentrations of therapeutic drugs presents special problems when these drugs are metabolized to compounds that have pharmacologic activity. This presentation reviews several methods for evaluating the pharmacologic activity of drug metabolites and describes the impact of active drug metabolites on the pharmacokinetic design of dose regimens and on the formulation of guidelines for plasma level interpretation. Lidocaine and monoethylglycinexylidide illustrate the considerations that pertain when both a drug and its active metabolite have similar therapeutic and toxic actions. Procainamide and N-acetylprocainamide exemplify the much more complex situation that arises when a drug and its active metabolite have different pharmacologic activity.

  4. Modeling of breath methane concentration profiles during exercise on an ergometer*

    Science.gov (United States)

    Szabó, Anna; Unterkofler, Karl; Mochalski, Pawel; Jandacka, Martin; Ruzsanyi, Vera; Szabó, Gábor; Mohácsi, Árpád; Teschl, Susanne; Teschl, Gerald; King, Julian

    2016-01-01

    We develop a simple three compartment model based on mass balance equations which quantitatively describes the dynamics of breath methane concentration profiles during exercise on an ergometer. With the help of this model it is possible to estimate the endogenous production rate of methane in the large intestine by measuring breath gas concentrations of methane. PMID:26828421

  5. Profile of People Who Inject Drugs in Tehran, Iran

    Directory of Open Access Journals (Sweden)

    Masoumeh Amin-Esmaeili

    2017-01-01

    Full Text Available The marked shift in the patterns of drug use in Iran, from opium smoking to injecting drug use, has led to serious health-related outcomes. This study was designed to explore characteristics of people who inject drugs (PWID in Tehran, Iran. Nine hundred and four PWID were recruited from treatment and harm reduction facilities, as well as drug user hangouts in public areas in Tehran. Participants were interviewed using the Persian version of the World Health Organization Drug Injecting Study Phase II questionnaire. The median age at the time of the first illegal drug use, at the time of the first injection and current age was 20, 24 and 32, respectively. In more than 80% of the cases, the first drug used was opium. The transition from the first drug use to the first drug injection occurred after an average of 6.6 and 2.7 years for those who had started drug use with opium and heroin, respectively. Two-thirds of the participants shared injecting equipment within the last 6 months. Difficulty in obtaining sterile needles and thehigh cost of syringes were reported as the major reasons for needle/syringe sharing. Approximately 80% of community-recruited PWID reported difficulties in using treatment or harm reduction services. Self-detoxification and forced detoxification were the most common types of drug abuse treatment in alifetime. Despite a dramatic shift in drug policy in Iran during the past few years, wider coverage of harm reduction services, improvement of the quality of services, and education about such services are still necessary.

  6. Enantiomeric profiling of chiral drugs in wastewater and receiving waters

    OpenAIRE

    Kasprzyk-Hordern, Barbara; Baker, D R

    2012-01-01

    The aim of this paper is to discuss the enantiomer-specific fate of chiral drugs during wastewater treatment and in receiving waters. Several chiral drugs were studied: amphetamine-like drugs of abuse (amphetamine, methamphetamine, MDMA, MDA), ephedrines (ephedrine and pseudoephedrine), antidepressant venlafaxine, and beta-blocker atenolol. A monitoring program was undertaken in 7 WWTPs (utilizing mainly activated sludge and trickling filters technologies) and at 6 sampling points in receivin...

  7. Probing the carrier concentration profiles in phosphorus-implanted germanium using infrared spectroscopic ellipsometry

    Science.gov (United States)

    D'Costa, Vijay Richard; Yeo, Yee-Chia

    2015-02-01

    Spectroscopic ellipsometry with photon energy in the 0.045-0.65 eV range was used to investigate germanium samples implanted with 30 keV phosphorus ions and annealed at 700 °C. The infrared response of implanted layers is dominated by free carrier absorption which is modeled using a Drude oscillator. The carrier concentration profiles were modeled using an error function, and compared with those obtained by electrochemical capacitance-voltage profiling and secondary ion mass spectrometry. In the flat region of the carrier concentration profile, average carrier concentration and mobility of 1.40 × 1019 cm-3 and 336 cm2V-1s-1, respectively, were obtained. A phosphorus diffusivity of ˜1.2 × 10-13 cm2/s was obtained. The mobility versus carrier concentration relationships obtained for the implanted samples are close to the empirical relationship for bulk Ge.

  8. Importance of Drug Concentrations and Nutritional Status During ...

    African Journals Online (AJOL)

    The concentrations of CQ and sulfadoxine (S) were determined by HPLC in 100μl of capillary blood on filter paper. Multiple logistic regressions were used to determine associations with outcomes. Stunting (height-for-age <-2 Z-scores) was more common (27.7%) compared to underweight (wt-for-age <-2 Z-scores, 19.3%) ...

  9. Profiling of drug action using reporter mice and molecular imaging.

    Science.gov (United States)

    Rando, Gianpaolo; Biserni, Andrea; Ciana, Paolo; Maggi, Adriana

    2010-01-01

    Reporter mice associated to molecular imaging represent a major asset for the study of the spatio-temporal effects of drugs in living animals. The field is still relatively young and so far the number of animals genetically modified to express a given reporter gene ubiquitously and under the control of specific drugs is still limited. For a reporter animal the indispensable elements for the application to drug research and development are (i) the short life of the reporter enabling to have a clear view of the onset as well as the termination of drug effects, (ii) the generalized, drug-dependent activation of the reporter, and (iii) imaging modality suitable for high-throughput analysis. Because of its relative cheapness and ease to perform, in addition to all the above considerations, bioluminescence-based imaging is now regarded as the best imaging technology to be applied to the field of drug research. We show here the application of reporter mouse systems for drug screening in living animals in order to compare drug potency on target and specificity of action.

  10. Incidence microbiological profile and drug resistance pattern of ...

    African Journals Online (AJOL)

    Klebsiella was the most commonest uropathogen found in our study followed by Enterococcus , E.coli and Pseudomonas. E.coli and Pseudomonas showed high rates of drug resistance. Nitrofurantoin and Amikacin was the most effective drugs for majority of the isolates. Hence routine monitoring and screening for ASB in ...

  11. Tissue concentration-time profile of selenium after sodium selenite administration to rats

    International Nuclear Information System (INIS)

    Kaneko, Megumi; Natsuhori, Masahiro; Ito, Nobuhiko; Sera, Koichiro; Futatsugawa, Shoji

    1999-01-01

    Selenium (Se) concentration-time profiles in plasma and organs including liver, kidney, heart, lung, spleen and brain of rats (Jcl Wister, 9 wks old, n=32) were investigated after a single intravenous (iv) / oral (po) administration of sodium selenite (dose is equivalent to 2 mg/kg b.w. of Se). The Se concentration was determined by PIXE analysis. Among the investigated biological samples, Se concentration was the highest in the kidney or liver, followed by the heart, lung or spleen, then plasma, and the brain. Se concentrations in these organs were 0.5 to 5 times of plasma Se. The distribution profiles of Se in the organs were dependent on the route of administration. Furthermore, their profiles appeared almost parallel to the plasma Se-concentration in a logarithmic scale. Compared to the Se concentration-time profiles in plasma and organs by the route of administration, po group showed about 1/4-1/2 of the Se concentration in iv group except for kidney. Kidney kept relatively higher concentration of Se, which was similar in the both groups. This may explain our recently published data that urinary excretion was similar in the both groups. The relative oral bioavailability of plasma and each organ was calculated by the ratio of area under the concentration-time curve after oral administration (AUCpo) to AUCiv. Each organ appeared to have their own bioavailability (i.e., liver 39%, kidney 97%, heart 37%, lung 18%, spleen 10%, and brain 72%), where plasma was 46%. These results highly suggested that different Se distribution in organs by the different route of administration was due to the different metabolic profile. (author)

  12. Texture profile in processed cheese: influence of the use of milk protein concentrates and whey protein concentrates

    Directory of Open Access Journals (Sweden)

    Alisson Borges Souza

    2014-07-01

    Full Text Available The techno-functional properties of proteins related with the molecular characteristics are facilitated by partial unfolding of structures. From these interactions, the medium pH is presented as a major interferer in intensity and type of reaction that takes place. The intensity of denaturation and interaction of different proteins occur in different forms and intensity accordingly to the pH value of the medium in which they are located. This study aimed to verify the influence of interactions between whey protein concentrate/milk protein concentrate on the evolution of the texture profile of processed cheese at different pH values. We have analyzed samples of commercial whey protein concentrate (WPC and milk protein concentrate (MPC using 112.5g/kg processed cheese. The results were interpreted in terms of texture profile. It was also possible to optimize the different proportions of WPC and MPC, and pH value change the parameters of texture for creamy processed cheese and the pH was also an influencing factor in this optimization.

  13. Anticancer drugs in Portuguese surface waters - Estimation of concentrations and identification of potentially priority drugs.

    Science.gov (United States)

    Santos, Mónica S F; Franquet-Griell, Helena; Lacorte, Silvia; Madeira, Luis M; Alves, Arminda

    2017-10-01

    Anticancer drugs, used in chemotherapy, have emerged as new water contaminants due to their increasing consumption trends and poor elimination efficiency in conventional water treatment processes. As a result, anticancer drugs have been reported in surface and even drinking waters, posing the environment and human health at risk. However, the occurrence and distribution of anticancer drugs depend on the area studied and the hydrological dynamics, which determine the risk towards the environment. The main objective of the present study was to evaluate the risk of anticancer drugs in Portugal. This work includes an extensive analysis of the consumption trends of 171 anticancer drugs, sold or dispensed in Portugal between 2007 and 2015. The consumption data was processed aiming at the estimation of predicted environmental loads of anticancer drugs and 11 compounds were identified as potentially priority drugs based on an exposure-based approach (PEC b > 10 ng L -1 and/or PEC c > 1 ng L -1 ). In a national perspective, mycophenolic acid and mycophenolate mofetil are suspected to pose high risk to aquatic biota. Moderate and low risk was also associated to cyclophosphamide and bicalutamide exposition, respectively. Although no evidences of risk exist yet for the other anticancer drugs, concerns may be associated with long term effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Enantiomeric profiling of chiral illicit drugs in a pan-European study

    NARCIS (Netherlands)

    Castrignanò, E.; Yang, Z.; Bade, R.; Baz-Lomba, J.A.; Castiglioni, S.; Causanilles, A.; Covaci, A.; Gracia-Lor, E.; Hernández, F.; Kinyua, J.; McCall, A.-K.; van Nuijs, A.L.N.; Ort, C.; Plósz, B.G.; Ramin, P.; Rousis, N.I.; Ryu, Y.; Thomas, K.V.; de Voogt, P.; Zuccato, E.; Kasprzyk-Hordern, B.

    2018-01-01

    The aim of this paper is to present the first study on spatial and temporal variation in the enantiomeric profile of chiral drugs in eight European cities. Wastewater-based epidemiology (WBE) and enantioselective analysis were combined to evaluate trends in illicit drug use in the context of their

  15. Choice of capillary electrophoresis systems for the impurity profiling of drugs

    NARCIS (Netherlands)

    Hilhorst, M.J; Somsen, G.W; de Jong, G.J.

    In order to develop a strategy for the impurity profiling of drugs, the possibilities of some capillary electrophoresis systems were investigated. A mixture containing a drug and some of its possible impurities has been used as a model problem. The test compounds were investigated by capillary zone

  16. Chemometrics for drug impurity profiling : optimisation of capillary electrophoresis and deconvolution of overlapping peaks

    NARCIS (Netherlands)

    Zomeren, Paul Vincent van

    2008-01-01

    The potential of chemometrics for drug impurity profiling has been examined in this thesis. Generally, various hyphenated methods are used for the analysis of drug sub¬stance and product in order to enable the identification and quantification of impuri¬ties. chemometrics can be used to enhance the

  17. Identification of drug targets by chemogenomic and metabolomic profiling in yeast

    KAUST Repository

    Wu, Manhong

    2012-12-01

    OBJECTIVE: To advance our understanding of disease biology, the characterization of the molecular target for clinically proven or new drugs is very important. Because of its simplicity and the availability of strains with individual deletions in all of its genes, chemogenomic profiling in yeast has been used to identify drug targets. As measurement of drug-induced changes in cellular metabolites can yield considerable information about the effects of a drug, we investigated whether combining chemogenomic and metabolomic profiling in yeast could improve the characterization of drug targets. BASIC METHODS: We used chemogenomic and metabolomic profiling in yeast to characterize the target for five drugs acting on two biologically important pathways. A novel computational method that uses a curated metabolic network was also developed, and it was used to identify the genes that are likely to be responsible for the metabolomic differences found. RESULTS AND CONCLUSION: The combination of metabolomic and chemogenomic profiling, along with data analyses carried out using a novel computational method, could robustly identify the enzymes targeted by five drugs. Moreover, this novel computational method has the potential to identify genes that are causative of metabolomic differences or drug targets. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

  18. Metabolic profile of amphetamine and methamphetamine following administration of the drug famprofazone.

    Science.gov (United States)

    Greenhill, Brandy; Valtier, Sandra; Cody, John T

    2003-10-01

    There are a several drugs that lead to the production of methamphetamine and/or amphetamine in the body which are subsequently excreted in the urine. These drugs raise obvious concerns when interpreting positive amphetamine drug testing results. Famprofazone is an analgesic found in a multi-ingredient medication (Gewodin) used for pain relief. Two Gewodin tablets (50 mg of famprofazone) were administered orally to healthy volunteers with no history of amphetamine, methamphetamine, or famprofazone use. Following administration, urine samples were collected ad lib for up to six days, and pH, specific gravity, and creatinine values were determined. In order to determine the quantitative excretion profile of amphetamine and methamphetamine, samples were extracted using liquid-liquid extraction, derivatized with heptafluorobutyric anhydride, and analyzed by gas chromatography-mass spectrometry (GC-MS). The ions monitored were 91, 118, 240 for amphetamine and 254, 210, 118 for methamphetamine. Amphetamine-d(6) and methamphetamine-d(11) were used as internal standards. Peak concentrations for amphetamine ranged from 148 to 2271 ng/mL and for methamphetamine 615 to 7361 ng/mL. Concentrations of both compounds peaked between 3 and 7 h post-dose. Amphetamine and methamphetamine could be detected (limit of detection = 5 ng/mL) at 121 and 143 h post-dose, respectively. Using a cutoff of 500 ng/mL, all subjects had individual urine samples that tested positive. One subject had 14 samples above the cutoff with the last positive being detected over 48 h post-dose. The profile of methamphetamine and amphetamine enantiomers was also determined using liquid-liquid extraction, derivatization with N-trifluoroacetyl-l-prolyl chloride and analysis by GC-MS. Data showed the famprofazone metabolites amphetamine and methamphetamine to be both d- and l-enantiomers. The proportion of l-methamphetamine exceeded that of its d-enantiomer from the first sample collected. Initially, the

  19. Non-irritant concentrations and amounts of active ingredient in drug patch tests.

    Science.gov (United States)

    Brajon, Delphine; Menetre, Sophie; Waton, Julie; Poreaux, Claire; Barbaud, Annick

    2014-09-01

    Drug patch tests (DPTs) with medicaments suspected of causing an allergic reaction represent a method of diagnostic testing that is low risk; DPTs can reproduce delayed hypersensitivity to drugs, and entail only a moderate re-exposure of patients to potential offending drugs. We assessed the non-irritating concentrations of DPTs and determined the amounts of active ingredient (AI) contained in the drugs used in the tests. The objectives were to assess the non-irritating concentration of DPTs and determine the amounts of active ingredient (AI) contained in the drugs used in the tests. From a retrospective, single-centre study of all patients investigated during a 6-year period with a drug eruption, each potentially responsible drug was tested with the commercially available preparation diluted to 30% in water, petrolatum, or alcohol. Data collection was performed with a customized computer database. For each type of DPT studied, the numbers of positive and negative test results were recorded. The amount of AI contained in the DPT (as a percentage) was then calculated after weighing of each tablet. Of the 5558 DPTs studied, all were non-irritant. The average concentration of AI was 9.8%; 25% of DPTs had an AI concentration of concentration of > 16%. The AI concentration ranged from 0.05% (digoxin) to 30% (paracetamol lyophilisate). These data provide thresholds for the non-irritating concentration of AI of 68 different drugs, and thresholds for the non-irritating dilution for 82 drugs, and will help to standardize DPT methods. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Lung Tissue Concentrations of Pyrazinamide among Patients with Drug-Resistant Pulmonary Tuberculosis

    OpenAIRE

    Kempker, Russell R.; Heinrichs, M. Tobias; Nikolaishvili, Ketino; Sabulua, Irina; Bablishvili, Nino; Gogishvili, Shota; Avaliani, Zaza; Tukvadze, Nestani; Little, Brent; Bernheim, Adam; Read, Timothy D.; Guarner, Jeannette; Derendorf, Hartmut; Peloquin, Charles A.; Blumberg, Henry M.

    2017-01-01

    Improved knowledge regarding the tissue penetration of antituberculosis drugs may help optimize drug management. Patients with drug-resistant pulmonary tuberculosis undergoing adjunctive surgery were enrolled. Serial serum samples were collected, and microdialysis was performed using ex vivo lung tissue to measure pyrazinamide concentrations. Among 10 patients, the median pyrazinamide dose was 24.7 mg/kg of body weight. Imaging revealed predominant lung lesions as cavitary (n = 6 patients), m...

  1. The frequency of drugs among Danish drivers before and after the introduction of fixed concentration limits

    DEFF Research Database (Denmark)

    Steentoft, Anni; Simonsen, Kirsten Wiese; Linnet, Kristian

    2010-01-01

    Until July 2007, the driving under the influence of drugs (DUID) legislation in Denmark was based on impairment, evaluated on the basis of a clinical investigation and toxicological analyses, but in 2007 fixed concentration limits were introduced into the Danish traffic legislation. The objective...... for this study was to investigate the prevalence of medication and illicit drugs among Danish drivers before and after 2007....

  2. Profiles of drug addicts in relation to personality variables and disorders.

    Science.gov (United States)

    Carou, María; Romero, Estrella; Luengo, Mª Ángeles

    2016-10-07

    In recent decades, research has identified a set of impulsive/disinhibited personality variables closely associated with drug addiction. As well as this, disorders linked with these variables, such as ADHD and personality disorders, are being closely studied in the field of drug addiction. Although much knowledge has been accumulated about the relation of these variables and disorders taken separately, less is known about how these constructs allow identify-specific profiles within the drug dependent population to be identified. This work, on the basis of data collected on a sample of drug addicts in treatment, analyzes how impulsiveness, sensation seeking, self-control, ADHD and personality disorders contribute to identifying specific profiles of addicts. Cluster analysis allowed two profiles to be outlined according to these personality and psychopathology characteristics. Self-control, impulsiveness, impulsive and antisocial personality disorders, as well as scores in ADHD, emerge as the variables that contribute more to profile differentiation. One of these profiles (56.1% of participants) with a high disinhibition pattern, is associated with severe indicators of consumption and criminal career patterns. These results allow us to emphasize the role of personality and impulsiveness-related disorders in the identification of distinctive profiles within the addict population, and suggest the need to generate treatment strategies adapted to personal/psychopathology configurations of drug addicts.

  3. Integrative relational machine-learning for understanding drug side-effect profiles.

    Science.gov (United States)

    Bresso, Emmanuel; Grisoni, Renaud; Marchetti, Gino; Karaboga, Arnaud Sinan; Souchet, Michel; Devignes, Marie-Dominique; Smaïl-Tabbone, Malika

    2013-06-26

    Drug side effects represent a common reason for stopping drug development during clinical trials. Improving our ability to understand drug side effects is necessary to reduce attrition rates during drug development as well as the risk of discovering novel side effects in available drugs. Today, most investigations deal with isolated side effects and overlook possible redundancy and their frequent co-occurrence. In this work, drug annotations are collected from SIDER and DrugBank databases. Terms describing individual side effects reported in SIDER are clustered with a semantic similarity measure into term clusters (TCs). Maximal frequent itemsets are extracted from the resulting drug x TC binary table, leading to the identification of what we call side-effect profiles (SEPs). A SEP is defined as the longest combination of TCs which are shared by a significant number of drugs. Frequent SEPs are explored on the basis of integrated drug and target descriptors using two machine learning methods: decision-trees and inductive-logic programming. Although both methods yield explicit models, inductive-logic programming method performs relational learning and is able to exploit not only drug properties but also background knowledge. Learning efficiency is evaluated by cross-validation and direct testing with new molecules. Comparison of the two machine-learning methods shows that the inductive-logic-programming method displays a greater sensitivity than decision trees and successfully exploit background knowledge such as functional annotations and pathways of drug targets, thereby producing rich and expressive rules. All models and theories are available on a dedicated web site. Side effect profiles covering significant number of drugs have been extracted from a drug ×side-effect association table. Integration of background knowledge concerning both chemical and biological spaces has been combined with a relational learning method for discovering rules which explicitly

  4. Parallel monitoring of plasma and intraluminal drug concentrations in man after oral administration of fosamprenavir in the fasted and fed state.

    Science.gov (United States)

    Brouwers, Joachim; Tack, Jan; Augustijns, Patrick

    2007-10-01

    The purpose of this study was to explore the feasibility of linking the pharmacokinetic profile of a drug with its gastrointestinal behavior by simultaneously monitoring plasma and intraluminal drug concentrations. Fosamprenavir, a phosphate ester prodrug of the poorly water-soluble HIV-inhibitor amprenavir, was selected as model compound. A single tablet of fosamprenavir (Telzir) was administered to 5 volunteers in the fasted and fed state (simulated by intake of a nutritional drink). Gastric and duodenal fluids were aspirated in function of time and characterized with respect to the concentration of (fos)amprenavir, inorganic phosphate and pH. In parallel, blood samples were collected and analyzed for amprenavir. The observed plasma concentration-time profiles suggested a food-induced delay in the absorption of amprenavir: in the fed state, mean tmax increased by more than 150 min compared to the fasted state. A similar delay was seen in the duodenal appearance of fosamprenavir (concentrations in mM-range) and, after dephosphorylation, amprenavir (concentrations below 160 microM). This observation could be related to the behavior of fosamprenavir in the stomach. In the fasted state, gastric dissolution of fosamprenavir started immediately, resulting in a Cmax of 4 +/- 2 mM after 43 +/- 15 min; however, in the fed state, the fosamprenavir concentration remained below 20 microM for the first 90 min after drug intake. The postponed gastric dissolution may be attributed to a food-induced delay in tablet disintegration. For the first time, the pharmacokinetic profile of a drug was monitored in parallel with its gastrointestinal concentrations. The observed food effect in the plasma concentration-time profile of amprenavir after intake of its phosphate ester prodrug could be related to a food-induced delay in gastric dissolution of fosamprenavir.

  5. Multi-analytical approach for profiling some essential medical drugs

    International Nuclear Information System (INIS)

    Abubakar, M.

    2015-07-01

    Counterfeit and substandard pharmaceutical drugs are chiefly rampant in developing countries due to inadequate analytical facilities and lack of regulatory oversight. The production of counterfeit or substandard drugs is broadly problematic. Underestimating it therefore leads to morbidity, mortality, drug resistance, introduction of toxic substances into the body and loss of confidence in health care systems. Medical drugs that are often counterfeited range from antimalarial drugs to antiretroviral drugs with antibiotics being counterfeited the most. This research work, therefore, aims at contributing towards the establishment of measures/processes for distinguishing between fake and genuine amoxicillin drugs. This was achieved by the identification and quantification of the Active Pharmaceutical Ingredient (API) and the excipients in the drug formulation. The major analytical techniques employed for this research work were Instrumental Neutron Activation Analysis (INAA), X-ray Powder Diffraction (XRD), High Performance Liquid Chromatography (HPLC) and in vitro Dissolution Test. The amoxicillin samples analyzed were the foreign generic amoxicillin purchased from Ernest Chemists pharmacy at East Legon, Accra, the National Health Insurance Scheme (NHIS) amoxicillin purchased at Fair Mile pharmacy at West Legon, Accra and the Suspected Fake amoxicillin purchased at Okaishi market. For the establishment of fingerprint for identification of substandard amoxicillin, INAA was used to qualitatively determine the short lived radionuclides (excipients) which then facilitated the correct identification of the API and the excipient phases in each of the amoxicillin groups. The phases identified were Amoxicillin Trihydrate as the excipient, Magnesium Stearate (hydrated) and Magnesium Stearate (anhydrous) as the excipients. For Quality control purposes, High Performance Liquid Chromatography approach and also, the in vitro Dissolution test were conducted on each of the groups of

  6. Determining concentration depth profiles in fluorinated networks by means of electric force microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Miccio, Luis A. [Institute of Materials Science and Technology (INTEMA), University of Mar del Plata and National Research Council (CONICET), JB. Justo 4302, Mar del Plata, Buenos Aires (Argentina); Centro de Fisica de Materiales CSIC-UPV/EHU, Materials Physics Center (MPC), Paseo Manuel de Lardizabal 5, 20018 San Sebastian (Spain); Kummali, Mohammed M.; Alegria, Angel [Centro de Fisica de Materiales CSIC-UPV/EHU, Materials Physics Center (MPC), Paseo Manuel de Lardizabal 5, 20018 San Sebastian (Spain); Departamento de Fisica de Materiales UPV/EHU, Facultad de Quimica, 20080 San Sebastian (Spain); Montemartini, Pablo E.; Oyanguren, Patricia A. [Institute of Materials Science and Technology (INTEMA), University of Mar del Plata and National Research Council (CONICET), JB. Justo 4302, Mar del Plata, Buenos Aires (Argentina); Schwartz, Gustavo A. [Centro de Fisica de Materiales CSIC-UPV/EHU, Materials Physics Center (MPC), Paseo Manuel de Lardizabal 5, 20018 San Sebastian (Spain); Colmenero, Juan [Centro de Fisica de Materiales CSIC-UPV/EHU, Materials Physics Center (MPC), Paseo Manuel de Lardizabal 5, 20018 San Sebastian (Spain); Departamento de Fisica de Materiales UPV/EHU, Facultad de Quimica, 20080 San Sebastian (Spain); Donostia International Physics Center, Paseo Manuel de Lardizabal 4, 20018 San Sebastian (Spain)

    2011-08-14

    By means of electric force microscopy, composition depth profiles were measured with nanometric resolution for a series of fluorinated networks. By mapping the dielectric permittivity along a line going from the surface to the bulk, we were able to experimentally access to the fluorine concentration profile. Obtained data show composition gradient lengths ranging from 30 nm to 80 nm in the near surface area for samples containing from 0.5 to 5 wt. % F, respectively. In contrast, no gradients of concentration were detected in bulk. This method has several advantages over other techniques because it allows profiling directly on a sectional cut of the sample. By combining the obtained results with x-ray photoelectron spectroscopy measurements, we were also able to quantify F/C ratio as a function of depth with nanoscale resolution.

  7. Estimation of the degree of authenticity of concentrational element profile derived from RBS measurements

    International Nuclear Information System (INIS)

    Egorov, V.K.; Okhulkov, A.V.

    1993-01-01

    A simple technique is offered for estimating the degree of authenticity of element concentrational profile which does not depend on the complicated character of RBS spectra and possible intercorrelation of parameters. The technique can be implemented with any program simulating RBS spectra, for instance, RUMP. 5 refs.; 1 fig.; 1 tab

  8. Ion-beam-induced migration and its effect on concentration profiles

    International Nuclear Information System (INIS)

    Myers, S.M.

    1979-01-01

    The mechanisms by which ion irradiation influences atomic transport are reviewed, including cascade mixing, enhanced diffusion via mobile point defects, rapid diffusion along extended defects, and solute trapping at irradiation damage. The effects of these processes on measured concentration profiles are considered for high-energy ion beam analysis

  9. Pentobarbital self-administration in rhesus monkeys: drug concentration and fixed-ratio size interactions.

    OpenAIRE

    Lemaire, G A; Meisch, R A

    1984-01-01

    Performances of three rhesus monkeys were reinforced by the oral delivery of pentobarbital and studied as functions of fixed-ratio size and drug concentration. Pentobarbital solutions and water were concurrently available on identical reinforcement schedules from separate liquid-delivery systems during 3-hour sessions. Under a fixed-ratio 16 schedule of drug availability, a descending series of drug concentrations was tested (4, 2, 1, 0.5, 0.25, 0.125, and 0.0625 mg/ml, followed by a retest a...

  10. Linking Suspension Nasal Spray Drug Deposition Patterns to Pharmacokinetic Profiles: A Proof-of-Concept Study Using Computational Fluid Dynamics.

    Science.gov (United States)

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

    2016-06-01

    The objective of this study was to link regional nasal spray deposition patterns of suspension formulations, predicted with computational fluid dynamics, to in vivo human pharmacokinetic plasma concentration profiles. This is accomplished through the use of computational fluid dynamics simulations coupled with compartmental pharmacokinetic modeling. Results showed a rapid initial rise in plasma concentration that is due to the absorption of drug particles deposited in the nasal middle passages, followed by a slower increase in plasma concentration that is governed by the transport of drug particles from the nasal vestibule to the middle passages. Although drug deposition locations in the nasal cavity had a significant effect on the shape of the concentration profile, the absolute bioavailability remained constant provided that all the drug remained in the nose over the course of the simulation. Loss of drug through the nostrils even after long periods resulted in a significant decrease in bioavailability and increased variability. The results of this study quantify how differences in nasal drug deposition affect transient plasma concentrations and overall bioavailability. These findings are potentially useful for establishing bioequivalence for nasal spray devices and reducing the burden of in vitro testing, pharmacodynamics, and clinical studies. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  11. Binding kinetics of five drugs to beta2-adrenoceptor using peak profiling method and nonlinear chromatography.

    Science.gov (United States)

    Liang, Yuan; Wang, Jing; Fei, Fuhuan; Sun, Huanmei; Liu, Ting; Li, Qian; Zhao, Xinfeng; Zheng, Xiaohui

    2018-02-23

    Investigations of drug-protein interactions have advanced our knowledge of ways to design more rational drugs. In addition to extensive thermodynamic studies, ongoing works are needed to enhance the exploration of drug-protein binding kinetics. In this work, the beta2-adrenoceptor (β 2 -AR) was immobilized on N, N'-carbonyldiimidazole activated amino polystyrene microspheres to prepare an affinity column (4.6 mm × 5.0 cm, 8 μm). The β 2 -AR column was utilized to determine the binding kinetics of five drugs to the receptor. Introducing peak profiling method into this receptor chromatographic analysis, we determined the dissociation rate constants (k d ) of salbutamol, terbutaline, methoxyphenamine, isoprenaline hydrochloride and ephedrine hydrochloride to β 2 -AR to be 15 (±1), 22 (±1), 3.3 (±0.2), 2.3 (±0.2) and 2.1 (±0.1) s -1 , respectively. The employment of nonlinear chromatography (NLC) in this case exhibited the same rank order of k d values for the five drugs bound to β 2 -AR. We confirmed that both the peak profiling method and NLC were capable of routine measurement of receptor-drug binding kinetics. Compared with the peak profiling method, NLC was advantageous in the simultaneous assessment of the kinetic and apparent thermodynamic parameters. It will become a powerful method for high throughput drug-receptor interaction analysis. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Bradsim-prediction of solute concentration. Temperature and physical property profiles along pulsed plate columns

    International Nuclear Information System (INIS)

    Logsdail, D.H.; Evans, S.F.; Jenkins, J.A.; Smith, I.J.

    1988-01-01

    Dynamic model of the operation of the BRADSIM pulsed plate column is developed. Examples of simulation of the pures process extraction system are given. Profiles of dissolved substances concentrations and profiles of physical properties of liquid along the column are provided. Calculated values are compared with the experimental data, obtained in case of the column 50 mm in diameter, Harwell extractional facility and Sellafield pulsed column 300 mm in diameter for extraction systems uranyl nitrate-nitric acid-20% and 30% TBP in kerosene. 2 refs.; 6 figs

  13. Characterizing contaminant concentrations with depth by using the USGS well profiler in Oklahoma, 2003-9

    Science.gov (United States)

    Smith, S. Jerrod; Becker, Carol J.

    2011-01-01

    Since 2003, the U.S. Geological Survey (USGS) Oklahoma Water Science Center has been using the USGS well profiler to characterize changes in water contribution and contaminant concentrations with depth in pumping public-supply wells in selected aquifers. The tools and methods associated with the well profiler, which were first developed by the USGS California Water Science Center, have been used to investigate common problems such as saline water intrusion in high-yield irrigation wells and metals contamination in high-yield public-supply wells.

  14. Cure of tuberculosis despite serum concentrations of antituberculosis drugs below published reference ranges.

    Science.gov (United States)

    Meloni, Monica; Corti, Natascia; Müller, Daniel; Henning, Lars; Gutteck, Ursula; von Braun, Amrei; Weber, Rainer; Fehr, Jan

    2015-01-01

    Therapeutic target serum concentrations of first-line antituberculosis drugs have not been well defined in clinical studies in tuberculosis (TB) patients. We retrospectively investigated the estimated maximum serum concentrations (eC max) of antituberculosis drugs and clinical outcome of TB patients with therapeutic drug monitoring performed between 2010-2012 at our institution, and follow-up until March 2014. The eC max was defined as the highest serum concentration during a sampling period (2, 4 and 6 hours after drug ingestion). We compared the results with published eC max values, and categorised them as either "within reference range", "low eC max", or "very low eC max".Low/very low eC max-levels were defined as follows: isoniazid 2-3/max levels were classified as "low" or "very low". The eC max was below the relevant reference range in 80% of isoniazid, 95% of rifampicin, 30% of pyrazinamide, and 30% of ethambutol measurements. All but one patient were cured of tuberculosis. Although many antituberculosis drug serum concentrations were below the widely used reference ranges, 16 of 17 patients were cured of tuberculosis. These results challenge the use of the published reference ranges for therapeutic drug monitoring.

  15. Behavioural profile of drug users attending public drug-treatment centres in Sicily: the role of social context

    Directory of Open Access Journals (Sweden)

    Francesco Vitale

    2007-12-01

    Full Text Available

    Objective: Investigations of injecting drug users (IDUs have suggested that the social context may influence high-risk behaviours in this population. The aim of this study was to describe knowledge, attitudes and behaviours of IDUs attending public drug-treatment centres in our area.

    Study design and methods: A cross-sectional survey was conducted between July 2002 and February 2004, enrolling 607 drug users attending four public drug-treatment centres in the Palermo area. Two of them were located inside the urban area, whereas the other two were in rural districts near the city. All participants answered an anonymous questionnaire concerning social and demographic characteristic and potential high-risk behaviours.

    Results: IDUs living in urban context have a higher educational level, higher number of sexual partners, as well as a lower prevalence of exchanging sex for drugs. Conversely, IDUs living in suburban/rural context are less likely to share syringes and more likely to have used light drugs in the past. Suburban/rural IDUs drink more alcohol but smoke less cigarettes/day, although both groups are strong smokers.

    Conclusions: The results suggest that public drug-treatment centres should take in consideration the adoption of specific programs targeting specific groups, in line with the profile and needs of the subjects in each context in order to promote approaches leading to risk reduction.

  16. 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...

  17. HT-SPOTi: A Rapid Drug Susceptibility Test (DST) to Evaluate Antibiotic Resistance Profiles and Novel Chemicals for Anti-Infective Drug Discovery.

    Science.gov (United States)

    Danquah, Cynthia A; Maitra, Arundhati; Gibbons, Simon; Faull, Jane; Bhakta, Sanjib

    2016-02-08

    Antibiotic resistance is one of the major threats to global health and well-being. The past decade has seen an alarming rise in the evolution and spread of drug-resistant strains of pathogenic microbes. The emergence of extensively drug resistant (XDR) strains of Mycobacterium tuberculosis and antimicrobial resistance among the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species) as well as fungal pathogens (such as certain species of Candida, Aspergillus, Cryptococcus, and Trichophyton) poses a significant 21st century scientific challenge. With an extremely limited arsenal of efficacious antibiotics, techniques that can (a) identify novel antimicrobials and (b) detect antimicrobial resistance are becoming increasingly important. In this article, we illustrate the HT-SPOTi, an assay that is principally based on the growth of an organism on agar medium containing a range of different concentrations of drugs or inhibitors. The simple methodology makes this assay ideal for evaluating novel antimicrobial compounds as well as profiling an organism's antibiotic resistance profile. Copyright © 2016 John Wiley & Sons, Inc.

  18. Hypnosis control based on the minimum concentration of anesthetic drug for maintaining appropriate hypnosis.

    Science.gov (United States)

    Furutani, Eiko; Nishigaki, Yuki; Kanda, Chiaki; Takeda, Toshihiro; Shirakami, Gotaro

    2013-01-01

    This paper proposes a novel hypnosis control method using Auditory Evoked Potential Index (aepEX) as a hypnosis index. In order to avoid side effects of an anesthetic drug, it is desirable to reduce the amount of an anesthetic drug during surgery. For this purpose many studies of hypnosis control systems have been done. Most of them use Bispectral Index (BIS), another hypnosis index, but it has problems of dependence on anesthetic drugs and nonsmooth change near some particular values. On the other hand, aepEX has an ability of clear distinction between patient consciousness and unconsciousness and independence of anesthetic drugs. The control method proposed in this paper consists of two elements: estimating the minimum effect-site concentration for maintaining appropriate hypnosis and adjusting infusion rate of an anesthetic drug, propofol, using model predictive control. The minimum effect-site concentration is estimated utilizing the property of aepEX pharmacodynamics. The infusion rate of propofol is adjusted so that effect-site concentration of propofol may be kept near and always above the minimum effect-site concentration. Simulation results of hypnosis control using the proposed method show that the minimum concentration can be estimated appropriately and that the proposed control method can maintain hypnosis adequately and reduce the total infusion amount of propofol.

  19. [Detection of Carbon Dioxide Concentration in Soil Profile Based on Nondispersive Infrared Spectroscopy Technique].

    Science.gov (United States)

    Tu, Zhi-hua; Zhao, Yang; Zheng, Li-wen; Jia, Guo-dong; Chen, Li-hua; Yu, Xin-xiao

    2015-04-01

    In order to explore the variation of CO2 concentration and soil respiration in soil profile, the nondispersive infrared (NDIR) spectroscopy technique was applied to continually estimate the soil CO2 concentration in different soil layers (the humus horizon, A-, B-, C-horizon) in situ. The main instrument used in this experiment was silicon-based nondispersive infrared sensor, which could work in severe environment. We collected the Measurement value by NDIR spectroscopy technique throughout 2013. The values of soil carbon flux in different soil layers were calculated based on the model of gradient method and calibrated by measuring with an automated soil CO2 efflux system (LI-8100). The results showed that: a vertical gradient for the carbon dioxide concentration in soil profile was found, and the concentration was highest in the deepest soil horizon. Moreover, A linear correlation between the soil CO2 effluxes was calculated based on model and measurement, and the model prediction correlation coefficient was 0.9069, 0.7185, 0.8382, and 0.9030 in the H-, A-, B-, and C-horizon, respectively. The roots of mean square error (RMSE) were 0.2067, 0.1041, 0.0156, and 0.0096 in the H-, A-, B-, and C-horizon, respectively. These results suggest that the gradient method based on the NDIR spectroscopy technique can be successfully used to measure soil CO2 efflux in different soil layers, which reveal that diffusion and convection transport CO2 between the soil layers. It is a promising sensor for detecting CO2 concentration in soil profile, providing the basic data for calculating the global carbon in soil profile.

  20. [Predictive factors of drug prescription: profile of the overprescribing physician].

    Science.gov (United States)

    Espigares Arroyo, M; Montes Salas, G; Altimiras Roset, J; Iglesias Sánchez, J M; Brioso Jerez, F

    1994-01-01

    Because of increasing pharmaceutical costs, several programs aimed at optimizing physician's prescription have been set up in the last years. However, factors determining prescription volume are not well known yet. The aim of study is to determine which the characteristics of the practitioner (GP) or the working place are related with a higher amount of drug prescription. With data obtained from PE-29, PE-20, and the managing center Human Resources Department databases, concerning the whole GP staff (N = 293), via a multiple regression model, we were able to determine the following factors predicting higher prescription:rural work place, longer distance to reference specialty center, care to children, lack of postgraduate education, short term work contract, and part time staff.

  1. Drug utilization profile in adult patients with refractory epilepsy at a tertiary referral center

    OpenAIRE

    Freitas-Lima, Priscila de; Baldoni, Andre de Oliveira; Alexandre, Veriano; Pereira, Leonardo Regis Leira; Sakamoto, Americo Ceiki

    2013-01-01

    Objective To evaluate the utilization profile of antiepileptic drugs in a population of adult patients with refractory epilepsy attending a tertiary center. Method Descriptive analyses of data were obtained from the medical records of 112 patients. Other clinical and demographic characteristics were also registered. Results Polytherapies with ≥3 antiepileptic drugs were prescribed to 60.7% of patients. Of the old agents, carbamazepine and clobazam were the most commonly prescribed (72.3% ...

  2. Experimental and numerical results for CO2 concentration and temperature profiles in an occupied room

    Science.gov (United States)

    Cotel, Aline; Junghans, Lars; Wang, Xiaoxiang

    2014-11-01

    In recent years, a recognition of the scope of the negative environmental impact of existing buildings has spurred academic and industrial interest in transforming existing building design practices and disciplinary knowledge. For example, buildings alone consume 72% of the electricity produced annually in the United States; this share is expected to rise to 75% by 2025 (EPA, 2009). Significant reductions in overall building energy consumption can be achieved using green building methods such as natural ventilation. An office was instrumented on campus to acquire CO2 concentrations and temperature profiles at multiple locations while a single occupant was present. Using openFOAM, numerical calculations were performed to allow for comparisons of the CO2 concentration and temperature profiles for different ventilation strategies. Ultimately, these results will be the inputs into a real time feedback control system that can adjust actuators for indoor ventilation and utilize green design strategies. Funded by UM Office of Vice President for Research.

  3. Evaluation of drug toxicity profiles based on the phenotypes of ascidian Ciona intestinalis.

    Science.gov (United States)

    Mizotani, Yuji; Itoh, Shun; Hotta, Kohji; Tashiro, Etsu; Oka, Kotaro; Imoto, Masaya

    2015-08-07

    In vivo toxicity evaluation using model organisms is an important step for the development of new drugs. Here, we report that Ciona intestinalis, a chordate invertebrate, is beneficial to drug toxicity evaluation for the following reasons: rapid embryonic and larval development, resemblance to vertebrates, ease of management, low cost, transparent body, and low risk of ethical issues. The dynamic phenotypic change of Ciona larvae during metamorphosis prompted us to examine the effect of cytotoxic drugs on its development by quantifying six toxicity endpoints: degenerated tail size, ampulla length, rotation of body axis, stomach size, heart rate, and body size. As a result, mitochondrial respiratory inhibitors, tubulin polymerization/depolymerization inhibitors, or DNA/RNA synthesis inhibitors showed distinct toxicity profiles against these six endpoints, but drugs with the same targets showed a similar toxicity profile in Ciona. Our results suggest Ciona is an effective animal model for profiling drug toxicity and exploring the mechanisms of drugs with unknown targets. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Derangement of lipid profile in antiepileptic drugs treated patients in local population

    International Nuclear Information System (INIS)

    Zuberi, N.A.; Perveen, T.

    2012-01-01

    Epilepsy is the third most common neurological disorder. It is not a single entity. The abnormal electrical activity may result in a variety of events, including loss of consciousness, abnormal movements, a typical or odd behavior or distorted perceptions falls seizers. Epilepsy is a chronic disorder and often requiring years of treatment. A large number of drugs are used for the treatment of epilepsy. The choice among the antiepileptic drugs depends on its effectiveness and side effects. Our retrospective study investigated the effect of anti epileptic drugs on lipid profile. Serum lipid profile was measured in 160 patients in which 40 patients were not started any antiepileptic drug .The remaining 120 patients were receiving antiepileptic drugs (AEDs). 40 control subjects were taken from general population for comparison. The height, weight and body mass index (BMI) and lipid profile of antiepileptic drugs treated patients were compared with control and untreated group. The weight and body mass index of antiepileptic drugs treated group was significantly increased when compared to the control group. Total Cholesterol (TC), Triglyceride (TO), High density lipoprotein (HDL-C), low density lipoprotein (LDL-C), ratio TC/HDL-C and ratio LDL-C/HDL-C were investigated for each group of drugs and controls. TC, TO, LDL-C, ratio TC/HDL-C and ratio LDL-C/HDL-C were significantly increased in patients who were on AEDs when compared with control but HDL-C of all drug treated groups showed significantly decreased when compared with control group. There was significant change in lipid profile was seen in AEDs treated group when compared with control group. Ratio TC/HDL-C and ratio LDUHDL-C alteration showed the risk of atherosclerosis and cardiovascular diseases. Anti-epileptic drugs also alter the BMI and so it could potentially facilitate the development of diabetes mellitus. Our results additionally suggest that there is a need for careful monitoring of lipid profile in

  5. Association between the use of anticholinergic antiparkinson drugs and safety and receptor drug-binding profiles of antipsychotic agents.

    Science.gov (United States)

    Gjerden, Pål; Slørdal, Lars; Bramness, Jørgen G

    2009-12-01

    The use of anticholinergic antiparkinson drugs is almost exclusively confined to treating antipsychotic-induced extrapyramidal side effects (EPS). We investigated the prevalence of concomitant prescription of anticholinergics as a proxy for antipsychotic-induced EPS and compared variance in prevalence with differences in the assumed mechanisms of action of antipsychotics on central nervous system (CNS) transmitter systems (i.e., receptor drug-binding profiles). We paid special attention to potential differences between typical and atypical antipsychotics. Data were drawn from the Norwegian Prescription Database on sales of antipsychotic and anticholinergic antiparkinson drugs to a total of 57,130 outpatients in 2004. We assessed concomitant dispensations of antipsychotic and anticholinergic drugs and correlated the prevalence of concomitantly prescribed anticholinergics to previously assessed receptor-binding profiles of antipsychotics. The concurrent use of anticholinergics varied between 0.4% and 26.0% for patients using a single antipsychotic agent. The prevalence of anticholinergic comedication was more than twice as high in patients using two or more antipsychotic drugs. Four typical antipsychotics (fluphenazine, zuclopenthixol, haloperidol, and perphenazine) were associated with higher concomitant use of anticholinergics than the rest. For the remaining 14 antipsychotic agents, the difference between typical and atypical antipsychotics was neither pronounced nor systematic. A high degree of D2-receptor antagonism and a high 5-HT2A/D2-receptor-affinity ratio coincided with the use of anticholinergics. The liability of antipsychotic drugs to cause EPS seemed to vary considerably and largely independently of the distinction between typical and atypical antipsychotics.

  6. Mitochondrial Profiling of Acute Myeloid Leukemia in the Assessment of Response to Apoptosis Modulating Drugs.

    Science.gov (United States)

    Ishizawa, Jo; Kojima, Kensuke; McQueen, Teresa; Ruvolo, Vivian; Chachad, Dhruv; Nogueras-Gonzalez, Graciela M; Huang, Xuelin; Pierceall, William E; Dettman, E J; Cardone, Michael H; Shacham, Sharon; Konopleva, Marina; Andreeff, Michael

    2015-01-01

    BH3 profiling measures the propensity of transformed cells to undergo intrinsic apoptosis and is determined by exposing cells to BH3-mimicking peptides. We hypothesized that basal levels of prosurvival BCL-2 family proteins may modulate the predictive power of BH3 profiling and termed it mitochondrial profiling. We investigated the correlation between cell sensitivity to apoptogenic agents and mitochondrial profiling, using a panel of acute myeloid leukemias induced to undergo apoptosis by exposure to cytarabine, the BH3 mimetic ABT-199, the MDM2 inhibitor Nutlin-3a, or the CRM1 inhibitor KPT-330. We found that the apoptogenic efficacies of ABT-199 and cytarabine correlated well with BH3 profiling reflecting BCL2, but not BCL-XL or MCL-1 dependence. Baseline BCL-2 protein expression analysis increased the ability of BH3 profiling to predict resistance mediated by MCL-1. By utilizing engineered cells with overexpression or knockdown of BCL-2 family proteins, Ara-C was found to be independent, while ABT-199 was dependent on BCL-XL. BCL-2 and BCL-XL overexpression mediated resistance to KPT-330 which was not reflected in the BH3 profiling assay, or in baseline BCL-2 protein levels. In conclusion, mitochondrial profiling, the combination of BH3 profiling and prosurvival BCL-2 family protein analysis, represents an improved approach to predict efficacy of diverse agents in AML and may have utility in the design of more effective drug combinations.

  7. Capillary electrokinetic separation techniques for profiling of drugs and related products

    NARCIS (Netherlands)

    Hilhorst, M.J; Somsen, G.W; de Jong, G.J.

    Capillary electrokinetic separation techniques offer high efficiency and peak capacity, and can be very useful for the analysis of samples containing a large variety of (unknown) compounds. Such samples are frequently met in impurity profiling of drugs (detection of potential impurities in a

  8. Anti-tuberculosis drug concentrations in tuberculosis patients with and without diabetes mellitus.

    Science.gov (United States)

    Kumar, A K Hemanth; Chandrasekaran, V; Kannan, T; Murali, A Lakshmi; Lavanya, J; Sudha, V; Swaminathan, Soumya; Ramachandran, Geetha

    2017-01-01

    The aim of the study was to compare plasma concentrations of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) between tuberculosis (TB) patients with and without diabetes mellitus (DM). Two-hour post-dosing concentrations of RMP, INH and PZA were determined in adult TB patients that were studied with (n = 452) and without DM (n = 1460), treated with a thrice-weekly regimen in India. Drug concentrations were estimated by HPLC. The median (IQR) INH [6.6 (3.9-10.0) and 7.8 (4.6-11.3)] and PZA [31.0 (22.3-38.0) and 34.1 (24.6-42.7)] microgram per milliliter concentrations were significantly lower in diabetic than non-diabetic TB patients (p < 0.001 for both drugs). Blood glucose was negatively correlated with plasma INH (r = -0.09, p < 0.001) and PZA (r = -0.092, p < 0.001). Multiple linear regression analysis showed RMP, INH and PZA concentrations were influenced by age and drug doses, INH and PZA by DM, RMP by alcohol use and PZA by gender and category of ATT. DM reduced INH and PZA concentrations by 0.8 and 3.0 μg/ml, respectively. TB patients with DM had lower INH and PZA concentrations. Negative correlation between blood glucose and drug concentrations suggests delayed absorption/faster elimination of INH and PZA in the presence of elevated glucose.

  9. Impact of the nature and concentration of plasticizers on the ability of PVC to sorb drug.

    Science.gov (United States)

    Al Salloum, H; Saunier, J; Aymes-Chodur, C; Barakat, H; Yagoubi, N

    2015-12-30

    The sorption of a drug by an infusion set may dramatically reduce the drug delivery efficiency. In this paper, we investigated how the drug sorption, in static conditions, is affected by the plasticizer's nature and ratio in the case of plasticized PVC, one of the most common material for infusion set tubing. Within the study, the drug concentration in diazepam solutions was studied after contact with PVC films containing different amounts of DEHP, DEHT, TOTM and DINCH® plasticizers. Moreover the partition coefficients between material and water were calculated. The drug sorption levels were equivalent for the different plasticizers and there was a plasticizer ratio for which the drug uptake was enhanced. As a consequence, the amount of sorbed drug might not be only linked to the amount of plasticizer in the film and to the solubility of the drug in the plasticizer alone: it must probably depend on specific interactions between plasticizer and PVC. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. An insight into the drug resistance profile & mechanism of drug resistance in Neisseria gonorrhoeae.

    Science.gov (United States)

    Patel, Achchhe Lal; Chaudhry, Uma; Sachdev, Divya; Sachdeva, Poonam Nagpal; Bala, Manju; Saluja, Daman

    2011-10-01

    Among the aetiological agents of treatable sexually transmitted diseases (STDs), Neissseria gonorrhoeae is considered to be most important because of emerging antibiotic resistant strains that compromise the effectiveness of treatment of the disease - gonorrhoea. In most of the developing countries, treatment of gonorrhoea relies mainly on syndromic management rather than the aetiological based therapy. Gonococcal infections are usually treated with single-dose therapy with an agent found to cure > 95 per cent of cases. Unfortunately during the last few decades, N. gonorrhoeae has developed resistance not only to less expensive antimicrobials such as sulphonamides, penicillin and tetracyclines but also to fluoroquinolones. The resistance trend of N. gonorrhoeae towards these antimicrobials can be categorised into pre-quinolone, quinolone and post-quinolone era. Among the antimicrobials available so far, only the third-generation cephalosporins could be safely recommended as first-line therapy for gonorrhoea globally. However, resistance to oral third-generation cephalosporins has also started emerging in some countries. Therefore, it has become imperative to initiate sustained national and international efforts to reduce infection and misuse of antibiotics so as to prevent further emergence and spread of antimicrobial resistance. It is necessary not only to monitor drug resistance and optimise treatment regimens, but also to gain insight into how gonococcus develops drug resistance. Knowledge of mechanism of resistance would help us to devise methods to prevent the occurrence of drug resistance against existing and new drugs. Such studies could also help in finding out new drug targets in N. gonorrhoeae and also a possibility of identification of new drugs for treating gonorrhoea.

  11. Profiling of some amoxicillin drugs in Ghana using Nuclear Magnetic Resonance Spectroscopy

    International Nuclear Information System (INIS)

    Aboagye, Mary Esi

    2016-07-01

    The prevalence of counterfeit drugs is seen as a problem faced in both developed and developing countries where Ghana is not an exception. Antibiotics are amongst the most counterfeit drugs in developing countries. What is less understood is that there are inadequate and ineffective quality control procedures in monitoring of drugs manufactured and imported into the country. This research work is aimed at contributing towards the development of routine analytical procedures that will facilitate distinguishing between fake and genuine amoxicillin drugs. This was accomplished by elaborating operating procedures for the analysis of specific antibiotic drug using nuclear magnetic resonance (NMR) spectroscopy and establishing the NMR profile of active principal ingredient (API) of amoxicillin drug and assessing the API in samples of amoxicillin drug purchased in Accra. Three brands of amoxicillin samples consisting of imported amoxicillin, National Health Insurance Scheme (NHIS) amoxicillin were purchased from a licensed pharmacy shop in Accra and amoxicillin purchased from Okaishie market were used for analysis. Standard amoxicillin known as amoxicillin trihydrate obtained from Ernest Chemist in Accra was also used analysed. The authenticity of the drugs was analysed using 1H and C-13 nuclear magnetic resonance spectroscopy. Upon analysis H-NMR and C-13 NMR profiles were obtained for the API (Amoxicillin Trihydrate) in amoxicillin. H NMR showed relatively higher sensitivities for the drug than C-13 NMR therefore analysis for the antibiotics was focused on H-NMR. After analysis amoxicillin trihydrate was identified as the API. A procedure suitable for NMR sample preparation of amoxicillin for NMR analysis was elaborated. Dimethyl sulfoxide was identified as a suitable solvent for the experiments. The samples were prepared by dissolving suitable quantities (10mg) of the drug in (1ml) of the chosen solvent. H-NMR technique was used to provide an NMR profile for the Active

  12. Rapid Identification of Potential Drugs for Diabetic Nephropathy Using Whole-Genome Expression Profiles of Glomeruli

    Directory of Open Access Journals (Sweden)

    Jingsong Shi

    2016-01-01

    Full Text Available Objective. To investigate potential drugs for diabetic nephropathy (DN using whole-genome expression profiles and the Connectivity Map (CMAP. Methodology. Eighteen Chinese Han DN patients and six normal controls were included in this study. Whole-genome expression profiles of microdissected glomeruli were measured using the Affymetrix human U133 plus 2.0 chip. Differentially expressed genes (DEGs between late stage and early stage DN samples and the CMAP database were used to identify potential drugs for DN using bioinformatics methods. Results. (1 A total of 1065 DEGs (FDR 1.5 were found in late stage DN patients compared with early stage DN patients. (2 Piperlongumine, 15d-PGJ2 (15-delta prostaglandin J2, vorinostat, and trichostatin A were predicted to be the most promising potential drugs for DN, acting as NF-κB inhibitors, histone deacetylase inhibitors (HDACIs, PI3K pathway inhibitors, or PPARγ agonists, respectively. Conclusion. Using whole-genome expression profiles and the CMAP database, we rapidly predicted potential DN drugs, and therapeutic potential was confirmed by previously published studies. Animal experiments and clinical trials are needed to confirm both the safety and efficacy of these drugs in the treatment of DN.

  13. Drug Release Profile from Calcium-Induced Alginate-Phosphate Composite Gel Beads

    Directory of Open Access Journals (Sweden)

    Yoshifumi Murata

    2009-01-01

    Full Text Available Calcium-induced alginate-phosphate composite gel beads were prepared, and model drug release profiles were investigated in vitro. The formation of calcium phosphate in the alginate gel matrix was observed and did not affect the rheological properties of the hydrogel beads. X-ray diffraction patterns showed that the calcium phosphate does not exist in crystalline form in the matrix. The initial release amount and release rate of a water-soluble drug, diclofenac, from the alginate gel beads could be controlled by modifying the composition of the matrix with calcium phosphate. In contrast, the release profile was not affected by the modification for hydrocortisone, a drug only slightly soluble in water.

  14. Numerical simulation of ozone concentration profile and flow characteristics in paddy bulks.

    Science.gov (United States)

    Pandiselvam, Ravi; Chandrasekar, Veerapandian; Thirupathi, Venkatachalam

    2017-08-01

    Ozone has shown the potential to control stored product insect pests. The high reactivity of ozone leads to special problems when it passes though an organic medium such as stored grains. Thus, there is a need for a simulation study to understand the concentration profile and flow characteristics of ozone in stored paddy bulks as a function of time. Simulation of ozone concentration through the paddy grain bulks was explained by applying the principle of the law of conservation along with a continuity equation. A higher ozone concentration value was observed at regions near the ozone diffuser whereas a lower concentration value was observed at regions away from the ozone diffuser. The relative error between the experimental and predicted ozone concentration values for the entire bin geometry was less than 42.8%. The simulation model described a non-linear change of ozone concentration in stored paddy bulks. Results of this study provide a valuable source for estimating the parameters needed for effectively designing a storage bin for fumigation of paddy grains in a commercial scale continuous-flow ozone fumigation system. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  15. TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models.

    Science.gov (United States)

    Yao, Zhi-Jiang; Dong, Jie; Che, Yu-Jing; Zhu, Min-Feng; Wen, Ming; Wang, Ning-Ning; Wang, Shan; Lu, Ai-Ping; Cao, Dong-Sheng

    2016-05-01

    Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com .

  16. TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models

    Science.gov (United States)

    Yao, Zhi-Jiang; Dong, Jie; Che, Yu-Jing; Zhu, Min-Feng; Wen, Ming; Wang, Ning-Ning; Wang, Shan; Lu, Ai-Ping; Cao, Dong-Sheng

    2016-05-01

    Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com.

  17. Modifications of sodium concentration profiles after electron and proton irradiation of glasses

    Energy Technology Data Exchange (ETDEWEB)

    Battaglin, G.; Delle Mea, G.; De Marchi, G.; Mazzoldi, P. (Padua Univ. (Italy). Ist. di Fisica); Puglisi, O. (Catania Univ. (Italy). Ist. Dipartimentale di Chimica e Chimica Industriale)

    1982-09-01

    The effect is reported of electron and proton irradiation on the depth distribution of sodium in commercial soda-lime glasses. Samples have been irradiated at different energies and fluences. The /sup 23/Na (p,..cap alpha..) /sup 20/Ne nuclear reaction has been used to determine the sodium profiles. No detectable changes in the sodium concentration profiles have been introduced during the measurements, the proton fluences and doses needed in this type of analysis being very low. The results obtained support the hypothesis that the driving force for Na diffusion is mainly connected to the build-up of an electric field whose direction is determined by the projectile charge, while Na mobility changes because of the local temperature increase due to the beam power dissipation.

  18. Diffusion-controlled spherulite growth in obsidian inferred from H2O concentration profiles

    Energy Technology Data Exchange (ETDEWEB)

    Watkins, Jim; Watkins, Jim; Manga, Michael; Huber, Christian; Martin, Michael C.

    2007-11-02

    Spherulites are spherical clusters of radiating crystals that occur naturally in rhyolitic obsidian. The growth of spherulites requires diffusion and uptake of crystal forming components from the host rhyolite melt or glass, and rejection of non-crystal forming components from the crystallizing region. Water concentration profiles measured by synchrotron-source Fourier transform spectroscopy reveal that water is expelled into the surrounding matrix during spherulite growth, and that it diffuses outward ahead of the advancing crystalline front. We compare these profiles to models of water diffusion in rhyolite to estimate timescales for spherulite growth. Using a diffusion-controlled growth law, we find that spherulites can grow on the order of days to months at temperatures above the glass transition. The diffusion-controlled growth law also accounts for spherulite size distribution, spherulite growth below the glass transition, and why spherulitic glasses are not completely devitrified.

  19. Influence of polymethacrylates and compritol on release profile of a highly water soluble drug metformin hydrochloride

    Directory of Open Access Journals (Sweden)

    Sunita Dahiya

    2015-01-01

    Full Text Available Aims: The present investigation studied effect of polymethacrylates Eudragit RSPO, Eudragit RLPO and compritol 888 ATO on release profile of highly water soluble drug metformin hydrochloride (MET. Materials and Methods: The solid dispersions were prepared using drug:polymer ratios 1:1 and 1:5 by coevaporation and coprecipitation techniques. Solid dispersions were characterized by infrared Spectroscopy (IR, differential scanning calorimetry (DSC, X-ray diffractometry (XRD as well as content uniformity, in vitro dissolution studies in 0.1 N HCl pH 1.2, phosphate buffer pH 6.8. Results and Discussion: Results of the studies suggested that there were progressive disappearance or changes of prominent peaks in IR, X-ray diffraction and thermotropic drug signals in coevaporates and coprecipitates with increased amount of polymers. Moreover, the in vitro release of highly water soluble MET could be extended at higher drug:polymer ratios. Conclusion: It was summarized that Eudragit RLPO had greater capacity of drug release than Eudragit RSPO and Comproitol 888 and its coevaporates in 1:5 drug:polymer ratio (F11 displayed extended drug release with comparatively higher dissolution rates (92.15 % drug release at 12 hour following near Zero order kinetics (r² =0.9822.

  20. Computational Analysis of Epidermal Growth Factor Receptor Mutations Predicts Differential Drug Sensitivity Profiles toward Kinase Inhibitors.

    Science.gov (United States)

    Akula, Sravani; Kamasani, Swapna; Sivan, Sree Kanth; Manga, Vijjulatha; Vudem, Dashavantha Reddy; Kancha, Rama Krishna

    2018-01-31

    A significant proportion of patients with lung cancer carry mutations in the EGFR kinase domain. The presence of a deletion mutation in exon 19 or L858R point mutation in the EGFR kinase domain has been shown to cause enhanced efficacy of inhibitor treatment in patients with NSCLC. Several less frequent (uncommon) mutations in the EGFR kinase domain with potential implications in treatment response have also been reported. The role of a limited number of uncommon mutations in drug sensitivity was experimentally verified. However, a huge number of these mutations remain uncharacterized for inhibitor sensitivity or resistance. A large-scale computational analysis of clinically reported 298 point mutants of EGFR kinase domain has been performed, and drug sensitivity profiles for each mutant toward seven kinase inhibitors has been determined by molecular docking. In addition, the relative inhibitor binding affinity toward each drug as compared with that of adenosine triphosphate was calculated for each mutant. The inhibitor sensitivity profiles predicted in this study for a set of previously characterized mutants correlated well with the published clinical, experimental, and computational data. Both the single and compound mutations displayed differential inhibitor sensitivity toward first- and next-generation kinase inhibitors. The present study provides predicted drug sensitivity profiles for a large panel of uncommon EGFR mutations toward multiple inhibitors, which may help clinicians in deciding mutant-specific treatment strategies. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  1. Doxorubicin-Loaded QuadraSphere Microspheres: Plasma Pharmacokinetics and Intratumoral Drug Concentration in an Animal Model of Liver Cancer

    International Nuclear Information System (INIS)

    Lee, Kwang-Hun; Liapi, Eleni A.; Cornell, Curt; Reb, Philippe; Buijs, Manon; Vossen, Josephina A.; Ventura, Veronica Prieto; Geschwind, Jean-Francois H.

    2010-01-01

    The purpose of this study was to evaluate, in vitro and in vivo, doxorubicin-loaded poly (vinyl alcohol-sodium acrylate) copolymer microspheres [QuadraSphere microspheres (QSMs)] for transcatheter arterial delivery in an animal model of liver cancer. Doxorubicin loading efficiency and release profile were first tested in vitro. In vivo, 15 rabbits, implanted with a Vx-2 tumor in the liver, were divided into three groups of five rabbits each, based on the time of euthanasia. Twenty-five milligrams of QSMs was diluted in 10 ml of a 10 mg/ml doxorubicin solution and 10 ml of nonionic contrast medium for a total volume of 20 ml. One milliliter of a drug-loaded QSM solution containing 5 mg of doxorubicin was injected into the tumor feeding artery. Plasma doxorubicin and doxorubicinol concentrations, and intratumoral and peritumoral doxorubicin tissue concentrations, were measured. Tumor specimens were pathologically evaluated to record tumor necrosis. As a control, one animal was blandly embolized with plain QSMs in each group. In vitro testing of QSM doxorubicin loadability and release over time showed 82-94% doxorubicin loadability within 2 h and 6% release within the first 6 h after loading, followed by a slow release pattern. In vivo, the doxorubicin plasma concentration declined at 40 min. The peak doxorubicin intratumoral concentration was observed at 3 days and remained detectable till the study's end point (7 days). Mean percentage tumor cell death in the doxorubicin QSM group was 90% at 7 days and 60% in the bland QSM embolization group. In conclusion, QSMs can be efficiently loaded with doxorubicin. Initial experiments with doxorubicin-loaded QSMs show a safe pharmacokinetic profile and effective tumor killing in an animal model of liver cancer.

  2. Determination of the concentration profile of chemical elements in superheater pipes

    International Nuclear Information System (INIS)

    Aldape U, F.; Aspiazu F, J.

    1986-05-01

    This work has for object to determine the profile of concentration of chemical elements at trace level in a superheater pipe of Thermoelectric Plants using the X-ray emission spectroscopy technique induced by protons coming from the Accelerator of the Nuclear Center. In the X-ray detection, a Si Li detector was used. The technique was chosen because it allows a multielemental analysis, of high sensitivity and precision. The results can help to understand the problems that are had in the change of flexibility or of corrosion. This will be from utility to the Federal Electricity Commission (CFE). (Author)

  3. Use of nuclear methods for the analysis of materials and the determination of concentration profiles

    International Nuclear Information System (INIS)

    Darras, R.

    1976-01-01

    The possibilities of the activation analysis and nuclear reaction analysis are presented. These methods allow the oligo-elements and impurities (in trace amounts) to be determined in materials with accuracy and a high sensitivity. They can also be applied to the determination of major elements in a small amount of materials. Surface analysis and concentration profile determination are possible when the nature and energy of the incident particles are judiciously selected. Exemples of analysis of steels, pure iron and refractories are given [fr

  4. Radon concentrations profiles over the brazilian Amazon basin during wet season

    International Nuclear Information System (INIS)

    Pereira, E.B.; Dias, P.L.S.; Nordemann, D.J.R.

    1991-01-01

    Atmospheric radon measurements were performed airborne in the Brazilian Amazon Basin during the wet season ABLE-2B experiment. The vertical profiles of radon showed a small decrease of concentration with increasing altitude at a rate varying from 6.5 to 11 x 10 - 2 Bq m - 3 km - 1. The calculation of the flux balance of radon in the troposphere above the Amazon Basin indicated a residual flux at the upper boundary of the measurement domain (6 km) of 0.14 atom cm - 2 s - 1. This residue may be associated with the turbulent transport of radon due to cloud activity. (author)

  5. The prediction of concentration profiles for a NIMCIX column absorbing uranium from aqueous solution

    International Nuclear Information System (INIS)

    Wright, R.S.

    1979-01-01

    A procedure is proposed for the prediction of concentration profiles for a countercurrent ion-exchange absorption column, use being made of equilibrium and kinetic data derived from small-scale batch tests. A comparison is presented between the predictions and the measured performance of a column (2,5 m in diameter) absorbing uranium from solution. The method is shown to be adequate for design purposes provided that the data used are from tests in which the solution and resin conditions approximate those for which the plant is being designed [af

  6. Therapeutic and toxic blood concentrations of nearly 1,000 drugs and other xenobiotics

    Science.gov (United States)

    2012-01-01

    Introduction In order to assess the significance of drug levels measured in intensive care medicine, clinical and forensic toxicology, as well as for therapeutic drug monitoring, it is essential that a comprehensive collection of data is readily available. Therefore, it makes sense to offer a carefully referenced compilation of therapeutic and toxic plasma concentration ranges, as well as half-lives, of a large number of drugs and other xenobiotics for quick and comprehensive information. Methods Data have been abstracted from original papers and text books, as well as from previous compilations, and have been completed with data collected in our own forensic and clinical toxicology laboratory. The data presented in the table and corresponding annotations have been developed over the past 20 years and longer. A previous compilation has been completely revised and updated. In addition, more than 170 substances, especially drugs that have been introduced to the market since 2003 as well as illegal drugs, which became known to cause intoxications, were added. All data were carefully referenced and more than 200 new references were included. Moreover, the annotations providing details were completely revised and more than 100 annotations were added. Results For nearly 1,000 drugs and other xenobiotics, therapeutic ("normal") and, if data were available, toxic and comatose-fatal blood-plasma concentrations and elimination half-lives were compiled in a table. Conclusions In case of intoxications, the concentration of the ingested substances and/or metabolites in blood plasma better predicts the clinical severity of the case when compared to the assumed amount and time of ingestion. Comparing and contrasting the clinical case against the data provided, including the half-life, may support the decision for or against further intensive care. In addition, the data provided are useful for the therapeutic monitoring of pharmacotherapies, to facilitate the diagnostic assessment

  7. A Novel 96well-formatted Micro-gap Plate Enabling Drug Response Profiling on Primary Tumour Samples

    Science.gov (United States)

    Ma, Wei-Yuan; Hsiung, Lo-Chang; Wang, Chen-Ho; Chiang, Chi-Ling; Lin, Ching-Hung; Huang, Chiun-Sheng; Wo, Andrew M.

    2015-04-01

    Drug-based treatments are the most widely used interventions for cancer management. Personalized drug response profiling remains inherently challenging with low cell count harvested from tumour sample. We present a 96well-formatted microfluidic plate with built-in micro-gap that preserves up to 99.2% of cells during multiple assay/wash operation and only 9,000 cells needed for a single reagent test (i.e. 1,000 cells per test spot x 3 selected concentration x triplication), enabling drug screening and compatibility with conventional automated workstations. Results with MCF7 and MDA-MB-231 cell lines showed that no statistical significance was found in dose-response between the device and conventional 96-well plate control. Primary tumour samples from breast cancer patients tested in the device also showed good IC50 prediction. With drug screening of primary cancer cells must consider a wide range of scenarios, e.g. suspended/attached cell types and rare/abundant cell availability, the device enables high throughput screening even for suspended cells with low cell count since the signature microfluidic cell-trapping feature ensures cell preservation in a multiple solution exchange protocol.

  8. Relationships of serum illicit drug concentrations during pregnancy to maternal nutritional status.

    Science.gov (United States)

    Knight, E M; James, H; Edwards, C H; Spurlock, B G; Oyemade, U J; Johnson, A A; West, W L; Cole, O J; Westney, L S; Westney, O E

    1994-06-01

    Findings reported are for a subset of African American subjects, residing in the urban area of Washington, D. C., who participated in a Program Project designed to study nutrition, other factors, and the outcome of pregnancy. Fasting blood samples, drawn during each trimester of pregnancy and at delivery, were screened for concentrations of cocaine, phencyclidine (PCP) and marijuana. Since substance abusers are expected to consume inadequate diets, these samples were also analyzed for serum folate, vitamin B12, ferritin and ascorbic acid. Data for these biochemical variables were compared for subjects whose serum values for drugs were either above or below the drug screening threshold concentrations established by ADAMHA/NIDA. Pearson's correlations were used to determine relationships between pregnancy outcome variables and maternal serum drug concentrations. Blood samples drawn at delivery showed higher maternal: cord ratios (mean +/- SEM) for marijuana (3.3 +/- 2.2) and PCP (2.9 +/- 1.0) than for cocaine (1.0 +/- 0.2). The subjects whose serum values were above the ADAMHA/NIDA ranges for marijuana, PCP and cocaine had concentrations of folate and ferritin that were significantly less than those of subjects with lower serum drug levels (P illicit drugs were accompanied by a significant increase in leukocyte count (P < or = 0.05). The level of maternal cocaine during the third trimester was inversely correlated with birthweight (r = -0.29; n = 52; P = 0.038) and head circumference (r = -0.28; n = 52; P = 0.047).(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Flexing the PECs: Predicting environmental concentrations of veterinary drugs in Canadian agricultural soils.

    Science.gov (United States)

    Kullik, Sigrun A; Belknap, Andrew M

    2017-03-01

    Veterinary drugs administered to food animals primarily enter ecosystems through the application of livestock waste to agricultural land. Although veterinary drugs are essential for protecting animal health, their entry into the environment may pose a risk for nontarget organisms. A means to predict environmental concentrations of new veterinary drug ingredients in soil is required to assess their environmental fate, distribution, and potential effects. The Canadian predicted environmental concentrations in soil (PECsoil) for new veterinary drug ingredients for use in intensively reared animals is based on the approach currently used by the European Medicines Agency for VICH Phase I environmental assessments. The calculation for the European Medicines Agency PECsoil can be adapted to account for regional animal husbandry and land use practices. Canadian agricultural practices for intensively reared cattle, pigs, and poultry differ substantially from those in the European Union. The development of PECsoil default values and livestock categories representative of typical Canadian animal production methods and nutrient management practices culminates several years of research and an extensive survey and analysis of the scientific literature, Canadian agricultural statistics, national and provincial management recommendations, veterinary product databases, and producers. A PECsoil can be used to rapidly identify new veterinary drugs intended for intensive livestock production that should undergo targeted ecotoxicity and fate testing. The Canadian PECsoil model is readily available, transparent, and requires minimal inputs to generate a screening level environmental assessment for veterinary drugs that can be refined if additional data are available. PECsoil values for a hypothetical veterinary drug dosage regimen are presented and discussed in an international context. Integr Environ Assess Manag 2017;13:331-341. © 2016 Her Majesty the Queen in Right of Canada

  10. Drug release profiles and microstructural characterization of cast and freeze dried vitamin B12 buccal films by positron annihilation lifetime spectroscopy.

    Science.gov (United States)

    Szabó, Barnabás; Kállai, Nikolett; Tóth, Gergő; Hetényi, Gergely; Zelkó, Romána

    2014-02-01

    Solvent cast and freeze dried films, containing the water-soluble vitamin B12 as model drug were prepared from two polymers, sodium alginate (SA), and Carbopol 71G (CP). The proportion of the CP was changed in the films. The microstructural characterization of various samples was carried out by positron annihilation lifetime spectroscopy (PALS). The drug release kinetics of untreated and stored samples was evaluated by the conventionally applied semi-empirical power law. Correlation was found between the changes of the characteristic parameters of the drug release and the ortho-positronium (o-Ps) lifetime values of polymer samples. The results indicated that the increase of CP concentration, the freeze-drying process and the storage at 75% R.H. decreased the rate of drug release. The PALS method enabled the distinction between the micro- and macrostructural factors influencing the drug release profile of polymer films. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Protein corona change the drug release profile of nanocarriers: the "overlooked" factor at the nanobio interface.

    Science.gov (United States)

    Behzadi, Shahed; Serpooshan, Vahid; Sakhtianchi, Ramin; Müller, Beate; Landfester, Katharina; Crespy, Daniel; Mahmoudi, Morteza

    2014-11-01

    The emergence of nanocarrier systems in drug delivery applications has ushered in rapid development of new classes of therapeutic agents which can provide an essential breakthrough in the fight against refractory diseases. However, successful clinical application of nano-drug delivery devices has been limited mainly due to the lack of control on sustained release of therapeutics from the carriers. A wide range of sophisticated approaches employs the formation of crosslinkable, non-crosslinkable, stimuli-responsive polymer nanocarriers in order to enhance their delivery efficiency. Despite the extensive research conducted on the development of various nanocarriers, the effect of the biological milieu on the drug release profile of these constructs is not yet fully investigated. In particular, the formation of a protein corona on the surface of nanocarriers, when they interact with living organisms in vivo is largely decisive for their biological function. Using a number of synthetized (i.e., superparamagnetic iron oxide nanoparticles and polymeric nanocapsules) and commercialized nanocarriers (i.e., Abraxane®, albumin-bound paclitaxel drug), this study demonstrates that the protein corona can shield the nanocarriers and, consequently, alters the release profile of the drugs from the nanocarriers. More specifically, the protein corona could significantly reduce the burst effect of either protein conjugated nanocarriers or carriers with surface loaded drug (i.e., SPIONs). However, the corona shell only slightly changed the release profile of polymeric nanocapsules. Therefore, the intermediary, buffer effect of the protein shells on the surface of nanoscale carriers plays a crucial role in their successful high-yield applications in vivo. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Thermal Profile of the Lunar Interior Constrained by Revised Estimates of Concentrations of Heat Producing Elements

    Science.gov (United States)

    Fuqua-Haviland, H.; Panovska, S.; Mallik, A.; Bremner, P. M.; McDonough, W. F.

    2017-12-01

    Constraining the heat producing element (HPE) concentrations of the Moon is important for understanding the thermal state of the interior. The lunar HPE budget is debated to be suprachondritic [1] to chondritic [2]. The Moon is differentiated, thus, each reservoir has a distinct HPE signature complicating this effort. The thermal profile of the lunar interior has been constructed using HPE concentrations of an ordinary chondrite (U = 0.0068 ppm; Th = 0.025 ppm; K = 17 ppm) which yields a conservative low estimate [2, 3, 4]. A later study estimated the bulk lunar mantle HPE concentrations (U = 0.039 ppm; Th = 0.15 ppm; K = 212 ppm) based on measurements of Apollo pyroclastic glasses [5] assuming that these glasses represent the least fractionated, near-primary lunar mantle melts, hence, are the best proxies for capturing mantle composition. In this study, we independently validate the revised estimate by using HPE concentrations [5] to construct a conductive lunar thermal profile, or selenotherm. We compare our conductive profile to the range of valid temperatures. We demonstrate the HPE concentrations reported by [5], when used in a simple 1D spherical thermal conduction equation, yield an impossibly hot mantle with temperatures in excess of 4,000 K (Fig 1). This confirms their revised estimate is not representative of the bulk lunar mantle, and perhaps only representative of a locally enriched mantle domain. We believe that their Low-Ti avg. source estimate (Th = 0.055 ppm, Th/U=4; K/U=1700), with the least KREEP assimilation is the closest representation of the bulk lunar mantle, producing 3E-12 W/kg of heat. This estimate is close to that of the Earth (5E-12 W/kg), indicating that the bulk Earth and lunar mantles are similar in their HPE constituents. We have used the lunar mantle heat production, in conjunction with HPE estimates of the Fe-Ti-rich cumulates (high Ti-source estimate from [5]) and measurements of crustal ferroan anorthite [6], to capture the

  13. Circulating Irisin Concentrations Are Associated with a Favourable Lipid Profile in the General Population.

    Directory of Open Access Journals (Sweden)

    Simon Oelmann

    Full Text Available Irisin is a myokine, which is mainly inversely associated with the risk for non-communicable diseases. Irisin improves cellular energy metabolism by uncoupling the mitochondrial respiratory chain resulting in increased energy expenditure using lipids. To date potential associations between irisin concentration and lipid profile are poorly understood. Therefore, this investigation aimed to evaluate potential associations between irisin and lipid levels in the general population.Data of 430 men and 537 women from the population-based Study of Health in Pomerania (SHIP-TREND with available irisin and lipid concentrations were used. Analyses of variance, linear and logistic regression models adjusted for age, HBA1c, waist circumference, physical activity, smoking, alcohol consumption, systolic blood pressure, ALAT were calculated.We detected significantly inverse associations between irisin and circulating levels of total [beta coefficient 0.21 (standard error 0.08, p = 0.01], low-density cholesterol [-0.16 (0.07, p = 0.03] and triglycerides [-0.17 (0.08, p = 0.02] for men. Females without lipid lowering medication had an inverse association between irisin and total cholesterol [-0.12 (0.06, p = 0.05]. Further, male subjects with irisin concentrations in the third tertile had an increased odds for elevated low-density cholesterol [odds ratio 1.96 (95% confidence interval 1.07-3.48, p = 0.03 and triglyceride [1.95 (1.09-3.47, p = 0.02] levels, even after exclusion of subjects with lipid lowering medication. In addition, our data revealed an annual rhythm of serum irisin levels with peak levels arise in winter and summer months.This is the first investigation to report a significant association between circulating irisin and a favourable lipid profile in the general population. This may infer that higher irisin concentrations are associated with a reduced risk for non-communicable diseases.

  14. Dynamic changes in amino acid concentration profiles in patients with sepsis.

    Directory of Open Access Journals (Sweden)

    Longxiang Su

    Full Text Available The goal of this work was to explore the dynamic concentration profiles of 42 amino acids and the significance of these profiles in relation to sepsis, with the aim of providing guidance for clinical therapies.Thirty-five critically ill patients with sepsis were included. These patients were further divided into sepsis (12 cases and severe sepsis (23 cases groups or survivor (20 cases and non-survivor (15 cases groups. Serum samples from the patients were collected on days 1, 3, 5, 7, 10, and 14 following intensive care unit (ICU admission, and the serum concentrations of 42 amino acids were measured.The metabolic spectrum of the amino acids changed dramatically in patients with sepsis. As the disease progressed further or with poor prognosis, the levels of the different amino acids gradually increased, decreased, or fluctuated over time. The concentrations of sulfur-containing amino acids (SAAs, especially taurine, decreased significantly as the severity of sepsis worsened or with poor prognosis of the patient. The serum concentrations of SAAs, especially taurine, exhibited weak negative correlations with the Sequential Organ Failure Assessment (SOFA (r=-0.319 and Acute Physiology and Chronic Health Evaluation (APACHE II (r=-0.325 scores. The areas under the receiver operating characteristic curves of cystine, taurine, and SAA levels and the SOFA and APACHE II scores, which denoted disease prognosis, were 0.623, 0.674, 0.678, 0.86, and 0.857, respectively.Critically ill patients with disorders of amino acid metabolism, especially of SAAs such as cystine and taurine, may provide an indicator of the need for the nutritional support of sepsis in the clinic.ClinicalTrial.gov identifier NCT01818830.

  15. Nitrogen concentration profiles in oxy-nitrited high-speed steel

    International Nuclear Information System (INIS)

    Barcz, A.; Turos, A.; Wielunski, L.

    1976-01-01

    Nuclear microanalysis has been applied for the determination of in-depth concentration profiles of nitrogen in oxy-nitrided high-speed steel. The concentration profiles were deduced from measurements of the nitrogen content, determined by means of the 14 N(d,α) 12 C reaction for the set of initially identical samples after the removal of surface layers of sequentially increasing thicknesses. The 1.2 MeV deuterons were obtained from the Institute of Nuclear Research Van de Graaf accelerator LECH. The α-particles produced in the 14 N(d,α) 12 C reaction were detected by means of silicon surface barrier detector mounted at 150 deg C. Strong blocking of the nitrogen diffusion due to the presence of oxygen has been observed. The accuracy of nitrogen detection is of the order of 5% for nitrogen-rich regions and 10% for the matrix. However, the local non-uniformity of the steel may cause a spread of about 20% of the measured values. (T.G.)

  16. Relationship between RFC gene expression and intracellular drug concentration in methotrexate-resistant osteosarcoma cells.

    Science.gov (United States)

    Wang, J J; Li, G J

    2014-07-24

    Osteosarcoma is a primary malignant tumor in adolescents, associated with high mortality and morbidity. The high-dose methotrexate (MTX) chemotherapy used to treat this disease may induce primary or secondary drug resistance, resulting in a reduced effect of comprehensive treatment. In this study, the relationship between reduced folate carrier (RFC) gene expression and intracellular drug concentration in MTX-resistant osteosarcoma cells (Saos-2) was investigated. MTX-resistant human osteosarcoma cells (Saos-2/MTX2.2, Saos-2/MTX4.4) were prepared. The sensitivities of Saos-2 (primary cells), Saos-2/MTX2.2, and Saos-2/MTX4.4 cells to MTX, diamminedichloroplatinum (DDP), ifosfamide (IFO), epirubicine (EPI), adriamycin (ADM), theprubicin (THP), and paclitaxel (PTX) were detected by MTT. The median inhibitory concentration (IC50) and resistance index were measured. Semi-quantitative RT-PCR was used to evaluate the expression of RFC gene in cells. The intracellular (3)H-MTX concentration was determined. Results showed that IC50 of Saos-2/MTX2.2 and Saos-2/MTX4.4 was 4.87 and 12.73 times that of Saos-2, respectively. Both Saos-2/MTX2.2 and Saos-2/MTX4.4 had resistance to IFO, ADM, EPI, THP, and PTX, but not DDP. Compared to Saos-2/MTX2.2 and Saos-2/MTX4.4, the expression of RFC mRNA in Saos-2 was significantly higher. The intracellular (3)H-MTX concentration reached a peak at 50 min. After 70 min, the concentration was maintained at a plateau. During this phase, the (3)H-MTX concentration in Saos-2 cells was 2.15 times higher than the concentration in Saos-2/MTX4.4 cells. The reduced RFC mRNA expression in PTX-resistant osteosarcoma cells may be related to the decrease in intracellular (3)H-MTX concentration.

  17. Cheburator software for automatically calculating drug inhibitory concentrations from in vitro screening assays.

    Directory of Open Access Journals (Sweden)

    Dmitry Nevozhay

    Full Text Available In the process of new cancer drug development, as the first step of their assessment, their activities are usually studied in vitro against a panel of cancer cell lines. The results of these in vitro drug screening assays are commonly expressed as inhibitory concentration 50% (IC50: the concentration of the tested agent that inhibits the proliferation of the cancer cell population to 50% of the theoretically possible effect (absolute IC50 or maximum effect practically achieved by the drug (relative IC50. The currently available software for calculating IC50 values requires manual data entry, is time consuming, and is prone to calculation errors. Thus, we have developed open source, free, easy-to-use software for performing standardized data evaluations and automatically calculating the IC50. This software eliminates the laborious and error-prone manual entry of data, substantially reduces the amount of time spent for data analysis. It has been extensively used in our department as the main tool for in vitro data processing during the past several years and can be useful for other research groups working in the area of anticancer drug discovery, either alone or combined with other software packages. The current version of our program, Cheburator, together with sample data, source code, and documentation, is freely available at the following URL: http://www.cheburator.nevozhay.com (it is free for academic use, but a license is required for commercial use.

  18. Global transcriptional profiling of longitudinal clinical isolates of Mycobacterium tuberculosis exhibiting rapid accumulation of drug resistance.

    Science.gov (United States)

    Chatterjee, Anirvan; Saranath, Dhananjaya; Bhatter, Purva; Mistry, Nerges

    2013-01-01

    The identification of multidrug resistant (MDR), extensively and totally drug resistant Mycobacterium tuberculosis (Mtb), in vulnerable sites such as Mumbai, is a grave threat to the control of tuberculosis. The current study aimed at explaining the rapid expression of MDR in Directly Observed Treatment Short Course (DOTS) compliant patients, represents the first study comparing global transcriptional profiles of 3 pairs of clinical Mtb isolates, collected longitudinally at initiation and completion of DOTS. While the isolates were drug susceptible (DS) at onset and MDR at completion of DOTS, they exhibited identical DNA fingerprints at both points of collection. The whole genome transcriptional analysis was performed using total RNA from H37Rv and 3 locally predominant spoligotypes viz. MANU1, CAS and Beijing, hybridized on MTBv3 (BuG@S) microarray, and yielded 36, 98 and 45 differentially expressed genes respectively. Genes encoding transcription factors (sig, rpoB), cell wall biosynthesis (emb genes), protein synthesis (rpl) and additional central metabolic pathways (ppdK, pknH, pfkB) were found to be down regulated in the MDR isolates as compared to the DS isolate of the same genotype. Up regulation of drug efflux pumps, ABC transporters, trans-membrane proteins and stress response transcriptional factors (whiB) in the MDR isolates was observed. The data indicated that Mtb, without specific mutations in drug target genes may persist in the host due to additional mechanisms like drug efflux pumps and lowered rate of metabolism. Furthermore this population of Mtb, which also showed reduced DNA repair activity, would result in selection and stabilization of spontaneous mutations in drug target genes, causing selection of a MDR strain in the presence of drug pressures. Efflux pump such as drrA may play a significant role in increasing fitness of low level drug resistant cells and assist in survival of Mtb till acquisition of drug resistant mutations with least

  19. Global transcriptional profiling of longitudinal clinical isolates of Mycobacterium tuberculosis exhibiting rapid accumulation of drug resistance.

    Directory of Open Access Journals (Sweden)

    Anirvan Chatterjee

    Full Text Available The identification of multidrug resistant (MDR, extensively and totally drug resistant Mycobacterium tuberculosis (Mtb, in vulnerable sites such as Mumbai, is a grave threat to the control of tuberculosis. The current study aimed at explaining the rapid expression of MDR in Directly Observed Treatment Short Course (DOTS compliant patients, represents the first study comparing global transcriptional profiles of 3 pairs of clinical Mtb isolates, collected longitudinally at initiation and completion of DOTS. While the isolates were drug susceptible (DS at onset and MDR at completion of DOTS, they exhibited identical DNA fingerprints at both points of collection. The whole genome transcriptional analysis was performed using total RNA from H37Rv and 3 locally predominant spoligotypes viz. MANU1, CAS and Beijing, hybridized on MTBv3 (BuG@S microarray, and yielded 36, 98 and 45 differentially expressed genes respectively. Genes encoding transcription factors (sig, rpoB, cell wall biosynthesis (emb genes, protein synthesis (rpl and additional central metabolic pathways (ppdK, pknH, pfkB were found to be down regulated in the MDR isolates as compared to the DS isolate of the same genotype. Up regulation of drug efflux pumps, ABC transporters, trans-membrane proteins and stress response transcriptional factors (whiB in the MDR isolates was observed. The data indicated that Mtb, without specific mutations in drug target genes may persist in the host due to additional mechanisms like drug efflux pumps and lowered rate of metabolism. Furthermore this population of Mtb, which also showed reduced DNA repair activity, would result in selection and stabilization of spontaneous mutations in drug target genes, causing selection of a MDR strain in the presence of drug pressures. Efflux pump such as drrA may play a significant role in increasing fitness of low level drug resistant cells and assist in survival of Mtb till acquisition of drug resistant mutations with

  20. 3D printing of tablets containing multiple drugs with defined release profiles.

    Science.gov (United States)

    Khaled, Shaban A; Burley, Jonathan C; Alexander, Morgan R; Yang, Jing; Roberts, Clive J

    2015-10-30

    We have employed three-dimensional (3D) extrusion-based printing as a medicine manufacturing technique for the production of multi-active tablets with well-defined and separate controlled release profiles for three different drugs. This 'polypill' made by a 3D additive manufacture technique demonstrates that complex medication regimes can be combined in a single tablet and that it is viable to formulate and 'dial up' this single tablet for the particular needs of an individual. The tablets used to illustrate this concept incorporate an osmotic pump with the drug captopril and sustained release compartments with the drugs nifedipine and glipizide. This combination of medicines could potentially be used to treat diabetics suffering from hypertension. The room temperature extrusion process used to print the formulations used excipients commonly employed in the pharmaceutical industry. Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) and X-ray powder diffraction (XRPD) were used to assess drug-excipient interaction. The printed formulations were evaluated for drug release using USP dissolution testing. We found that the captopril portion showed the intended zero order drug release of an osmotic pump and noted that the nifedipine and glipizide portions showed either first order release or Korsmeyer-Peppas release kinetics dependent upon the active/excipient ratio used. Copyright © 2015. Published by Elsevier B.V.

  1. Enantiomeric profiling of chiral illicit drugs in a pan-European study

    DEFF Research Database (Denmark)

    Castrignanò, Erika; Yang, Zhugen; Bade, Richard

    2018-01-01

    The aim of this paper is to present the first study on spatial and temporal variation in the enantiomeric profile of chiral drugs in eight European cities. Wastewater-based epidemiology (WBE) and enantioselective analysis were combined to evaluate trends in illicit drug use in the context...... of their consumption vs direct disposal as well as their synthetic production routes. Spatial variations in amphetamine loads were observed with higher use in Northern European cities. Enantioselective analysis showed a general enrichment of amphetamine with the R-(−)-enantiomer in wastewater indicating its abuse...... with the other cities tested. An enrichment of MDMA with the R-(−)-enantiomer was observed in European wastewaters indicating MDMA consumption rather than disposal of unused drug. MDA's chiral signature indicated its enrichment with the S-(+)-enantiomer, which confirms its origin from MDMA metabolism in humans...

  2. Spatial profiles of potential, ion concentration and flux in short unipolar and bipolar nanopores.

    Science.gov (United States)

    Tajparast, Mohammad; Virdi, Gautam; Glavinović, Mladen I

    2015-10-01

    During release of vesicular content the resistance of the fusion pore sometimes changes rapidly and repeatedly. However, it is not clear why the pore 'flickers'. Engineered nanopores often rectify, but how different factors influence the rectification requires clarification. To better understand the ionic 'causes' of pore conductivity and its changes we simulated ion transport through a short nanopore using Poisson-Nernst-Planck equations, coupling it to the transport of water using Navier-Stokes equations. We extracted the potential, concentration, and ion flux profiles. In uniformly charged nanopores the voltage bias determines which counter-ion flux dominates, and it is carried by the counter-ions of the highest concentration. In unipolar nanopores this simple rule breaks down. The dominant counter-ion in the charged half is from the adjacent compartment, but the bias determines what counter-ion flux is dominant--the same ion (regular bias), or a different and smaller (reverse bias), and this difference determines the level of rectification. In bipolar nanopores the dominant counter-ions in each half are from the adjacent compartments, and the total ion concentration dips in the middle near the wall. With regular bias the total ion concentration peaks in the pore center; the ions that carry the current through the nanopore start as counter-ions and their fluxes are large. With reverse bias the total concentration dips near the wall and in the center, both dominant ion fluxes through the nanopore start as co-ions and are very small, whereas those starting as counter-ions do not go through. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. The potential of LIRIC to validate the vertical profiles of the aerosol mass concentration estimated by an air quality model

    Science.gov (United States)

    Siomos, Nikolaos; Filoglou, Maria; Poupkou, Anastasia; Liora, Natalia; Dimopoulos, Spyros; Melas, Dimitris; Chaikovsky, Anatoli; Balis, Dimitris

    2015-04-01

    Vertical profiles of the aerosol mass concentration derived by a retrieval algorithm that uses combined sunphotometer and LIDAR data (LIRIC) were used in order to validate the mass concentration profiles estimated by the air quality model CAMx. LIDAR and CIMEL measurements of the Laboratory of Atmospheric Physics of the Aristotle University of Thessaloniki were used for this validation.The aerosol mass concentration profiles of the fine and coarse mode derived by CAMx were compared with the respective profiles derived by the retrieval algorithm. For the coarse mode particles, forecasts of the Saharan dust transportation model BSC-DREAM8bV2 were also taken into account. Each of the retrieval algorithm's profiles were matched to the models' profile with the best agreement within a time window of four hours before and after the central measurement. OPAC, a software than can provide optical properties of aerosol mixtures, was also employed in order to calculate the angstrom exponent and the lidar ratio values for 355nm and 532nm for each of the model's profiles aiming in a comparison with the angstrom exponent and the lidar ratio values derived by the retrieval algorithm for each measurement. The comparisons between the fine mode aerosol concentration profiles resulted in a good agreement between CAMx and the retrieval algorithm, with the vertical mean bias error never exceeding 7 μgr/m3. Concerning the aerosol coarse mode concentration profiles both CAMx and BSC-DREAM8bV2 values are severely underestimated, although, in cases of Saharan dust transportation events there is an agreement between the profiles of BSC-DREAM8bV2 model and the retrieval algorithm.

  4. Rapid identification of a Mycobacterium tuberculosis full genetic drug resistance profile through whole genome sequencing directly from sputum

    Directory of Open Access Journals (Sweden)

    Camus Nimmo

    2017-09-01

    Discussion: Compared to rapid molecular tests (which can only examine a limited number of mutations and WGS of culture isolates (which requires a culture step, WGS directly from sputum can quickly generate a complete genetic drug resistance profile. In this case, WGS altered the clinical management of drug-resistant tuberculosis and demonstrated potential for guiding individualized drug treatment where second-line drug resistance is common.

  5. Spectroscopic Analysis of Ion Concentration Profile at Electrode/Electrolyte Interface by Interferometry

    Science.gov (United States)

    Moore, David; Saraf, Ravi

    2014-03-01

    Owing to the difference in Fermi levels at an electrode/electrolyte interface, ions form an electrical double layer (EDL) with ion concentrations well over 10-fold compared to bulk. The concentration profile of the EDL intrinsically affects the electrochemical reaction rates at the electrode, which is of great significance in many applications, such as batteries and biosensors. Conventionally, using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), the electrical properties of the EDL are represented as ``equivalent circuits'' consisting of the resistance to charge transfer (Rct), the double layer capacitance (Cdl) and a ``Warburg (constant phase) diffusion element'' that represents the long range diffusion of ions to the electrode. The translation to the well-understood physical structure can be lost as complicated effects are often lumped together. For example, the effect of subtle modification of the electrode surface by say, redox compounds, enzymes, or polymers is not directly measured, and must be inferred by capacitance changes. An interferometer method will be described to directly measure changes in concentration at the interface during redox process. This method in concert with CV or EIS performed concomitantly will lead to more information to model the diffuse layer for improved understanding of the kinetics of the reaction at different distances from the electrode. Applications to DNA and polymer adsorption binding will be discussed.

  6. Mode of action classification of chemicals using multi-concentration time-dependent cellular response profiles.

    Science.gov (United States)

    Xi, Zhankun; Khare, Swanand; Cheung, Aaron; Huang, Biao; Pan, Tianhong; Zhang, Weiping; Ibrahim, Fadi; Jin, Can; Gabos, Stephan

    2014-04-01

    In this paper, we present a new statistical pattern recognition method for classifying cytotoxic cellular responses to toxic agents. The advantage of the proposed method is to quickly assess the toxicity level of an unclassified toxic agent on human health by bringing cytotoxic cellular responses with similar patterns (mode of action, MoOA) into the same class. The proposed method is a model-based hierarchical classification approach incorporating principal component analysis (PCA) and functional data analysis (FDA). The cytotoxic cell responses are represented by multi-concentration time-dependent cellular response profiles (TCRPs) which are dynamically recorded by using the xCELLigence real-time cell analysis high-throughput (RTCA HT) system. The classification results obtained using our algorithm show satisfactory discrimination and are validated using biological facts by examining common chemical mechanisms of actions with treatment on human hepatocellular carcinoma cells (HepG2). Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Influence of drugs of abuse and alcohol upon patients admitted to acute psychiatric wards: physician's assessment compared to blood drug concentrations.

    Science.gov (United States)

    Mordal, Jon; Medhus, Sigrid; Holm, Bjørn; Mørland, Jørg; Bramness, Jørgen G

    2013-06-01

    In acute psychiatric services, rapid and accurate detection of psychoactive substance intake may be required for appropriate diagnosis and intervention. The aim of this study was to investigate the relationship between (a) drug influence as assessed by physicians and (b) blood drug concentrations among patients admitted to acute psychiatric wards. We also explored the possible effects of age, sex, and psychotic symptoms on physician's assessment of drug influence. In a cross-sectional study, the sample comprised 271 consecutive admissions from 2 acute psychiatric wards. At admission, the physician on call performed an overall judgment of drug influence. Psychotic symptoms were assessed with the positive subscale of the Positive and Negative Syndrome Scale. Blood samples were screened for a wide range of psychoactive substances, and quantitative results were used to calculate blood drug concentration scores. Patients were judged as being under the influence of drugs and/or alcohol in 28% of the 271 admissions. Psychoactive substances were detected in 56% of the blood samples. Altogether, 15 different substances were found; up to 8 substances were found in samples from 1 patient. Markedly elevated blood drug concentration scores were estimated for 15% of the patients. Physician's assessment was positively related to the blood drug concentration scores (r = 0.52; P < 0.001), to symptoms of excitement, and to the detection of alcohol, cannabis, and amphetamines. The study demonstrates the major impact of alcohol and drugs in acute psychiatric settings and illustrates the challenging nature of the initial clinical assessment.

  8. Physiological concentrations of zinc reduce taurine-activated GlyR responses to drugs of abuse

    Science.gov (United States)

    Kirson, Dean; Cornelison, Garrett L.; Philpo, Ashley E.; Todorovic, Jelena; Mihic, S. John

    2013-01-01

    Taurine is an endogenous ligand acting on glycine receptors in many brain regions, including the hippocampus, prefrontal cortex, and nucleus accumbens (nAcc). These areas also contain low concentrations of zinc, which is known to potentiate glycine receptor responses. Despite an increasing awareness of the role of the glycine receptor in the rewarding properties of drugs of abuse, the possible interactions of these compounds with zinc has not been thoroughly addressed. Two-electrode voltage-clamp electrophysiological experiments were performed on α1, α2 α1β and a2β glycine receptors expressed in Xenopus laevis oocytes. The effects of zinc alone, and zinc in combination with other positive modulators on the glycine receptor, were investigated when activated by the full agonist glycine versus the partial agonist taurine. Low concentrations of zinc enhanced responses of maximally-effective concentrations of taurine but not glycine. Likewise, chelation of zinc from buffers decreased responses of taurine- but not glycine-mediated currents. Potentiating concentrations of zinc decreased ethanol, isoflurane, and toluene enhancement of maximal taurine currents with no effects on maximal glycine currents. Our findings suggest that the concurrence of high concentrations of taurine and low concentrations of zinc attenuate the effects of additional modulators on the glycine receptor, and that these conditions are more representative of in vivo functioning than effects seen when these modulators are applied in isolation. PMID:23973295

  9. CH4 concentrations over the Amazon from GOSAT consistent with in situ vertical profile data

    Science.gov (United States)

    Webb, Alex J.; Bösch, Hartmut; Parker, Robert J.; Gatti, Luciana V.; Gloor, Emanuel; Palmer, Paul I.; Basso, Luana S.; Chipperfield, Martyn P.; Correia, Caio S. C.; Domingues, Lucas G.; Feng, Liang; Gonzi, Siegfried; Miller, John B.; Warneke, Thorsten; Wilson, Christopher

    2016-09-01

    The Amazon Basin contains large wetland ecosystems which are important sources of methane (CH4). Spaceborne observations of atmospheric CH4 can provide constraints on emissions from these remote ecosystems, but lack of validation precludes robust estimates. We present the first validation of CH4 columns in the Amazon from the Greenhouse gases Observing SATellite (GOSAT) using aircraft measurements of CH4 over five sites across the Amazon Basin. These aircraft profiles, combined with stratospheric results from the TOMCAT chemical transport model, are vertically integrated allowing direct comparison to the GOSAT XCH4 measurements (the column-averaged dry air mole fraction of CH4). The measurements agree within uncertainties or show no significant difference at three of the aircraft sites, with differences ranging from -1.9 ppb to 6.6 ppb, while at two sites GOSAT XCH4 is shown to be slightly higher than aircraft measurements, by 8.1 ppb and 9.7 ppb. The seasonality in XCH4 seen by the aircraft profiles is also well captured (correlation coefficients from 0.61 to 0.90). GOSAT observes elevated concentrations in the northwest corner of South America in the dry season and enhanced concentrations elsewhere in the Amazon Basin in the wet season, with the strongest seasonal differences coinciding with regions in Bolivia known to contain large wetlands. Our results are encouraging evidence that these GOSAT CH4 columns are generally in good agreement with in situ measurements, and understanding the magnitude of any remaining biases between the two will allow more confidence in the application of XCH4 to constrain Amazonian CH4 fluxes.

  10. Safety profile of drugs used in the treatment of osteoporosis: a systematical review of the literature

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    M. Varenna

    2013-10-01

    Full Text Available The range of osteoporosis treatments is increasingly large and, like any disease, the pharmacological management of patients should involve a risk/benefit evaluation to attain the greatest reduction in risk of fracture with the lowest incidence of adverse events. The aim of this review is to critically appraise the literature about the safety issues of the main pharmacological treatments of osteoporosis. This document is the result of a consensus of experts based on a systematic review of regulatory documents, randomized controlled trials, metaanalyses, pharmacovigilance surveys and case series related to possible adverse drug reactions to osteoporosis treatment with calcium and vitamin D supplements, bisphosphonates, strontium ranelate, selective estrogen receptor modulators, denosumab, and teriparatide. As expected, randomized controlled trials showed only the most common adverse events due to the samples size and the short observation time. Case series and observational studies are able to provide data about uncommon side effects, but in some cases a sure cause-effect relationship needs still to be confirmed. Consistently with methodological limitations, the newer drugs have a tolerance profile that has not been fully explored yet. Osteoporosis treatments showed an overall good tolerance profile with rare serious adverse events that, however, must be well known by the clinician who prescribes these drugs. The concern about possible adverse events should be weighed against the reduction of morbidity and mortality associated with a significant fracture risk reduction.

  11. Solubility-pH profiles of some acidic, basic and amphoteric drugs.

    Science.gov (United States)

    Shoghi, Elham; Fuguet, Elisabet; Bosch, Elisabeth; Ràfols, Clara

    2013-01-23

    The solubility vs. pH profiles of five ionizable drugs of different nature (a monoprotic acid, a monoprotic base, a diprotic base and two amphoteric compounds showing a zwitterionic species each one) have been determined through two different methodologies: the classical shake-flask (S-F) and the potentiometric Cheqsol methods using in both instances the appropriate Henderson-Hasselbalch (H-H) or derived relationships. The results obtained independently from both approaches are consistent. A critical revision about the influence of the electrolyte used as buffering agent in the S-F method on the obtained solubility values is also performed. Thus, some deviations of the experimental points with respect the H-H profiles can be attributed to specific interactions between the buffering electrolyte and the drug due to the hydrotrophic character of citric and lactic acids. In other cases, the observed deviations are independent of the buffers used since they are caused by the formation of new species such as drug aggregates (cefadroxil) or the precipitation of a salt from a cationic species of the analyzed compound (quetiapine). Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Pb and Cd concentrations in a southern Bavarian bog profile and the history of vegetation as recorded by pollen analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kuester, H.; Rehfuess, K.-E. [Universitaet Muenchen, Muenchen (Germany). Inst. fuer Vor- und Fruehgeschichte

    1997-12-01

    In the lower part of a raised bog profile from Langegger Filz, southern Bavaria, the Pb and Cd concentrations were comparatively low while considerably higher concentrations of both elements were observed in the upper section of the profile. The peat layers with the highest concentrations of Pb and Cd were found to date from the Iron Age, the Roman Age, and the Middle Ages. The Fagus pollen curve reflects the beginning of a beech decline exactly in those peat layers in which the start of the Pb increase is visible. Therefore it appears that metal smelting caused a local release of heavy metals which were subsequently deposited in the raised bog. Metals could only be smelted when wood was cut and burned, and beech charcoal was preferred as it produces relatively high temperatures. The good agreement between the Pb concentration profile and the pollen analyses suggests that the bog provides an accurate record of atmospheric Pb deposition. 14 refs., 3 figs.

  13. Psychotropic drugs in mixture alter swimming behaviour of Japanese medaka (Oryzias latipes) larvae above environmental concentrations.

    Science.gov (United States)

    Chiffre, Axelle; Clérandeau, Christelle; Dwoinikoff, Charline; Le Bihanic, Florane; Budzinski, Hélène; Geret, Florence; Cachot, Jérôme

    2016-03-01

    Psychiatric pharmaceuticals, such as anxiolytics, sedatives, hypnotics and antidepressors, are among the most prescribed active substances in the world. The occurrence of these compounds in the environment, as well as the adverse effects they can have on non-target organisms, justifies the growing concern about these emerging environmental pollutants. This study aims to analyse the effects of six psychotropic drugs, valproate, cyamemazine, citalopram, sertraline, fluoxetine and oxazepam, on the survival and locomotion of Japanese medaka Oryzias latipes larvae. Newly hatched Japanese medaka were exposed to individual compounds for 72 h, at concentrations ranging from 10 μg L(-1) to 10 mg L(-1). Lethal concentrations 50 % (LC50) were estimated at 840, 841 and 9,136 μg L(-1) for fluoxetine, sertraline and citalopram, respectively, while other compounds did not induce any significant increase in mortality. Analysis of the swimming behaviour of larvae, including total distance moved, mobility and location, provided an estimated lowest observed effect concentration (LOEC) of 10 μg L(-1) for citalopram and oxazepam, 12.2 μg L(-1) for cyamemazine, 100 μg L(-1) for fluoxetine, 1,000 μg L(-1) for sertraline and >10,000 μg L(-1) for valproate. Realistic environmental mixture of the six psychotropic compounds induced disruption of larval locomotor behaviour at concentrations about 10- to 100-fold greater than environmental concentrations.

  14. Adequate plasma drug concentrations suggest that amoxicillin can be administered by continuous infusion using elastomeric pumps.

    Science.gov (United States)

    Arensdorff, Lyne; Boillat-Blanco, Noémie; Decosterd, Laurent; Buclin, Thierry; de Vallière, Serge

    2017-09-01

    Elastomeric pumps can be useful for the administration of antibiotics in the outpatient setting. To determine amoxicillin degradation in elastomeric pumps, as well as the effectiveness of amoxicillin treatment administered by elastomeric pumps. Antibiotic degradation was measured in elastomeric pumps filled with 6 g of amoxicillin in 240 mL of NaCl 0.9% by drawing samples at 12 h intervals when stored in the fridge for 48 h and when worn around the waist for 24 h. Subsequently nine patients were treated with continuous infusions of 8 or 12 g of amoxicillin per day. Plasma amoxicillin concentrations were measured on each visit to the outpatient parenteral antibiotic therapy unit. Clinical outcome was verified 3 months after the end of treatment. Amoxicillin degradation in elastomeric pumps reached 10% after 48 h in the fridge and an additional 30% when worn around the waist for 24 h. Mean plasma drug concentrations achieved with 12 g of amoxicillin per day were 18.5 mg/L (95% CI 13.5-23.5), which is largely above the MIC of amoxicillin-susceptible bacteria. Nine patients treated for various complicated infections were cured and had no unexpected adverse effects. Adequate plasma drug concentrations and favourable clinical outcomes suggest that amoxicillin can be administered by continuous infusion using elastomeric pumps. This treatment modality does not fulfil formal requirements regarding pharmaceutical stability, but the resulting safety impact in patients is probably limited. Therapeutic drug monitoring and a close clinical follow-up are recommended if this route of administration is chosen. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Dexamethasone-releasing cochlear implant coatings: application of artificial neural networks for modelling of formulation parameters and drug release profile.

    Science.gov (United States)

    Nemati, Pedram; Imani, Mohammad; Farahmandghavi, Farhid; Mirzadeh, Hamid; Marzban-Rad, Ehsan; Nasrabadi, Ali Motie

    2013-08-01

    Over the past few decades, mathematical modelling and simulation of drug delivery systems has been steadily gained interest as a focus for academic and industrial attention. Here, simulation of dexamethasone (DEX, a corticosteroid anti-inflammatory agent) release profile from drug-eluting cochlear implant coatings is reported using artificial neural networks. The devices were fabricated as monolithic dispersions of the pharmaceutically active ingredient in a silicone rubber matrix. A two-phase exponential model was fitted on the experimentally obtained DEX release profiles. An artificial neural network (ANN) was trained to determine formulation parameters (i.e. DEX loading percentage, the devices surface area and their geometry) for a specific experimentally obtained drug release profile. In a reverse strategy, an ANN was trained for determining expected drug release profiles for the same set of formulation parameters. An algorithm was developed by combining the two previously developed ANNs in a serial manner, and this was successfully used for simulating the developed drug-eluting cochlear implant coatings. The models were validated by a leave-one-out method and performing new experiments. The developed ANN algorithms were capable to bilaterally predict drug release profile for a known set of formulation parameters or find out the levels for input formulation parameters to obtain a desired DEX release profile. © 2013 Royal Pharmaceutical Society.

  16. Drug-drug interaction and doping, part 1: an in vitro study on the effect of non-prohibited drugs on the phase I metabolic profile of toremifene.

    Science.gov (United States)

    Mazzarino, Monica; de la Torre, Xavier; Fiacco, Ilaria; Palermo, Amelia; Botrè, Francesco

    2014-05-01

    The present study was designed to provide preliminary information on the potential impact of metabolic drug-drug interaction on the effectiveness of doping control strategies currently followed by the anti-doping laboratories to detect the intake of banned agents. In vitro assays based on the use of human liver microsomes and recombinant CYP isoforms were designed and performed to characterize the phase I metabolic profile of the prohibited agent toremifene, selected as a prototype drug of the class of selective oestrogen receptor modulators, both in the absence and in the presence of medicaments (fluconazole, ketoconazole, itraconazole, miconazole, cimetidine, ranitidine, fluoxetine, paroxetine, nefazodone) not included in the World Anti-Doping Agency list of prohibited substances and methods and frequently administered to athletes. The results show that the in vitro model developed in this study was adequate to simulate the in vivo metabolism of toremifene, confirming the results obtained in previous studies. Furthermore, our data also show that ketoconazole, itraconazole, miconazole and nefazodone cause a marked modification in the production of the metabolic products (i.e. hydroxylated and carboxylated metabolites) normally selected by the anti-doping laboratories as target analytes to detect toremifene intake; moderate variations were registered in the presence of fluconazole, paroxetine and fluoxetine; while no significant modifications were measured in the presence of ranitidine and cimetidine. This evidence imposes that the potential effect of drug-drug interactions is duly taken into account in anti-doping analysis, also for a broader significance of the analytical results. Copyright © 2014 John Wiley & Sons, Ltd.

  17. Profile of users intoxicated by drugs of abuse and association with death

    Directory of Open Access Journals (Sweden)

    Lúcia Margarete dos Reis

    2016-01-01

    Full Text Available Objective: to characterize the profile of users intoxicated by drugs of abuse reported to a center of information and toxicological assistance and related this to the occurrence of deaths. Methods: study of case series reported in the 2010-2011 biennium after active case finding. Data were obtained from epidemiological records filed in the center and submitted to univariate analysis, with chi-squared test and Fischer test. Results: three hundred and thirty nine cases were found, most were men (87.3%, with basic education (61.0% and elderly (37.2%. Alcohol use (83.8% and chronic intoxications (89.9% were predominant. Clinical complications were present in most medical diagnoses (63.4%. However, mortality was higher in the event deferral by cold and fire weapons. Conclusion: the consumption of drugs of abuse influences morbidity and mortality, particularly in men aged at 60 years or above and with low level of education.

  18. Profile of users intoxicated by drugs of abuse and association with death

    Directory of Open Access Journals (Sweden)

    Lúcia Margarete dos Reis

    2016-05-01

    Full Text Available Objective: to characterize the profile of users intoxicated by drugs of abuse reported to a center of information and toxicological assistance and related this to the occurrence of deaths. Methods: study of case series reported in the 2010-2011 biennium after active case finding. Data were obtained from epidemiological records filed in the center and submitted to univariate analysis, with chi-squared test and Fischer test. Results: three hundred and thirty nine cases were found, most were men (87.3%, with basic education (61.0% and elderly (37.2%. Alcohol use (83.8% and chronic intoxications (89.9% were predominant. Clinical complications were present in most medical diagnoses (63.4%. However, mortality was higher in the event deferral by cold and fire weapons. Conclusion: the consumption of drugs of abuse influences morbidity and mortality, particularly in men aged at 60 years or above and with low level of education.

  19. HIV Drug Resistance Profiles and Clinical Outcomes in Patients with Viremia Maintained at Very Low Levels

    Science.gov (United States)

    Jordan, Michael R; Winsett, Julie; Tiro, Aileen; Bau, Vuth; Berbara, Rony S; Rowley, Christopher; Bellosillo, Nobel; Wanke, Christine; Coakley, Eoin P

    2014-01-01

    We describe an observational study of clinical, virologic and drug resistance profiles in HIV-positive antiretroviral adherent subjects with stable low level viremia (LLV) 50–1,000 copies/mL for more than 12 months. Subjects were followed from time of first detectable viral load (VL). In total, 102 episodes of LLV were detected among 80 individuals. The median (mean, range) HIV copy number at genotyping was 250 (486, 1000 copies/mL (p=0.03). Our data suggest that DR present in patients with LLV is likely to impact long term clinical outcomes, highlighting the importance of optimizing techniques to detect the presence of drug resistant HIV in the setting of LLV and the need for larger prospective studies to assess the emergence of DR in the setting of sustained LLV and the impact of this DR on treatment outcomes. PMID:25664219

  20. Lifetime victimization and psychological distress: cluster profiles of out of treatment drug-involved women.

    Science.gov (United States)

    Golder, Seana; Logan, T K

    2010-01-01

    K-means clustering techniques were used to identify four cluster profiles characterized by unique patterns of victimization and psychological distress and further differentiated by distinct patterns of risk and protection across multiple life domains among a sample of 149 crack-using women. Results of this study suggest that important differences exist in patterns of victimization and psychological distress among drug-involved women. Identification of this variation can be used to tailor intervention strategies to the particular needs of different subgroups within the population of crack-using women.

  1. Citalopram and escitalopram plasma drug and metabolite concentrations: genome-wide associations.

    Science.gov (United States)

    Ji, Yuan; Schaid, Daniel J; Desta, Zeruesenay; Kubo, Michiaki; Batzler, Anthony J; Snyder, Karen; Mushiroda, Taisei; Kamatani, Naoyuki; Ogburn, Evan; Hall-Flavin, Daniel; Flockhart, David; Nakamura, Yusuke; Mrazek, David A; Weinshilboum, Richard M

    2014-08-01

    Citalopram (CT) and escitalopram (S-CT) are among the most widely prescribed selective serotonin reuptake inhibitors used to treat major depressive disorder (MDD). We applied a genome-wide association study to identify genetic factors that contribute to variation in plasma concentrations of CT or S-CT and their metabolites in MDD patients treated with CT or S-CT. Our genome-wide association study was performed using samples from 435 MDD patients. Linear mixed models were used to account for within-subject correlations of longitudinal measures of plasma drug/metabolite concentrations (4 and 8 weeks after the initiation of drug therapy), and single-nucleotide polymorphisms (SNPs) were modelled as additive allelic effects. Genome-wide significant associations were observed for S-CT concentration with SNPs in or near the CYP2C19 gene on chromosome 10 (rs1074145, P = 4.1 × 10(-9) ) and with S-didesmethylcitalopram concentration for SNPs near the CYP2D6 locus on chromosome 22 (rs1065852, P = 2.0 × 10(-16) ), supporting the important role of these cytochrome P450 (CYP) enzymes in biotransformation of citalopram. After adjustment for the effect of CYP2C19 functional alleles, the analyses also identified novel loci that will require future replication and functional validation. In vitro and in vivo studies have suggested that the biotransformation of CT to monodesmethylcitalopram and didesmethylcitalopram is mediated by CYP isozymes. The results of our genome-wide association study performed in MDD patients treated with CT or S-CT have confirmed those observations but also identified novel genomic loci that might play a role in variation in plasma levels of CT or its metabolites during the treatment of MDD patients with these selective serotonin reuptake inhibitors. © 2014 The British Pharmacological Society.

  2. From drug response profiling to target addiction scoring in cancer cell models

    Directory of Open Access Journals (Sweden)

    Bhagwan Yadav

    2015-10-01

    Full Text Available Deconvoluting the molecular target signals behind observed drug response phenotypes is an important part of phenotype-based drug discovery and repurposing efforts. We demonstrate here how our network-based deconvolution approach, named target addiction score (TAS, provides insights into the functional importance of druggable protein targets in cell-based drug sensitivity testing experiments. Using cancer cell line profiling data sets, we constructed a functional classification across 107 cancer cell models, based on their common and unique target addiction signatures. The pan-cancer addiction correlations could not be explained by the tissue of origin, and only correlated in part with molecular and genomic signatures of the heterogeneous cancer cells. The TAS-based cancer cell classification was also shown to be robust to drug response data resampling, as well as predictive of the transcriptomic patterns in an independent set of cancer cells that shared similar addiction signatures with the 107 cancers. The critical protein targets identified by the integrated approach were also shown to have clinically relevant mutation frequencies in patients with various cancer subtypes, including not only well-established pan-cancer genes, such as PTEN tumor suppressor, but also a number of targets that are less frequently mutated in specific cancer types, including ABL1 oncoprotein in acute myeloid leukemia. An application to leukemia patient primary cell models demonstrated how the target deconvolution approach offers functional insights into patient-specific addiction patterns, such as those indicative of their receptor-type tyrosine-protein kinase FLT3 internal tandem duplication (FLT3-ITD status and co-addiction partners, which may lead to clinically actionable, personalized drug treatment developments. To promote its application to the future drug testing studies, we have made available an open-source implementation of the TAS calculation in the form

  3. Time-course measurements of drug concentrations in hair and toenails after single administrations of pharmaceutical products.

    Science.gov (United States)

    Kuwayama, Kenji; Miyaguchi, Hajime; Iwata, Yuko T; Kanamori, Tatsuyuki; Tsujikawa, Kenji; Yamamuro, Tadashi; Segawa, Hiroki; Inoue, Hiroyuki

    2017-04-01

    Hair and nails are often used to prove long-term intake of drugs in forensic drug testing. The aim of this study was to evaluate the effectiveness of drug testing using hair and nails and the feasibility of determining when drugs were ingested by measuring the time-courses of drug concentrations in hair and toenails after single administrations of various drugs. Healthy subjects ingested four pharmaceutical products containing eight active ingredients in single doses. Hair and toenails were collected at predetermined intervals, and drug concentrations in hair and nails were measured for 12 months. The administered drugs and their main metabolites were extracted using micropulverized extraction with a stainless steel bullet and were analyzed using liquid chromatography/tandem mass spectrometry. Acidic compounds such as ibuprofen and its metabolites were not detected in both specimens. Acetaminophen, a weakly acidic compound, was detected in nails more frequently than in hair. The maximum concentration of allyl isopropyl acetylurea, a neutral compound, in nails was significantly higher than in hair. Nails are an effective specimen to detect neutral and weakly acidic compounds. For fexofenadine, a zwitterionic compound, and for most basic compounds, the maximum concentrations in hair segments tended to be higher than those in nails. The hair segments showing the maximum concentrations varied between drugs, samples, and subjects. Drug concentrations in hair segments greatly depended on the selection of the hair. Careful interpretation of analytical results is required to predict the time of drug intake. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  4. Comparison of effectiveness of acupuncture therapy and conventional drug therapy on psychological profile of migraine patients.

    Science.gov (United States)

    Vijayalakshmi, I; Shankar, N; Saxena, A; Bhatia, M S

    2014-01-01

    Migraine is a painful condition in which patients suffer from recurrent episodes of disabling pain, which could be very severe and can lead to grave psychological disturbances. There is no curative treatment for migraine, but there are various treatment modalities, though, with conflicting reports on their efficacy. This study was conducted to compare the effectiveness of electro acupuncture therapy and the conventional drug therapy on the psychological profile of migraneurs based on the assessment of quality of life and disability parameters. Migraneurs (n = 60) were recruited from the Psychiatry and Neurology OPD, Guru Tegh Bahadur Hospital, Delhi. Following a written consent, migraneurs were randomly allocated into 2 study groups--Group A received 10 sittings of electro acupuncture on selected acupuncture points over a period of 30 days, while for the same duration the Group D received a conventional drug therapy in the form of oral flunarizine 20 mg OD along with paracetamol 500 mg SOS. The patients were assessed twice, before and after completion of the treatment programme (30 days). The quality of life was assessed with WHOQOL BREF (WHO Quality of Life Biomedical Research and Education Foundation) questionnaire and the disability was assessed with MIDAS (Migraine Disability Assessment) questionnaire. Statistical analysis was performed using repeated measure's ANOVA with Tukey's test. Migraneurs were found to have lower quality of life and higher disability scores but following the treatment regimes, the 2 study groups showed a significant improvement in both the parameters studied. It was however observed, that the acupuncture group showed a better response and was thus found to be more effective as compared to the drug group (P = 0.005 to 0.000). We thus conclude that acupuncture is a better treatment option than the conventional drug therapy in not only relieving the pain of migraine but in also improving the psychological profile in migraneurs. Hence its

  5. Effects of Risperidone on Cytokine Profile in Drug-Naïve First-Episode Psychosis

    Science.gov (United States)

    Noto, Cristiano; Ota, Vanessa Kiyomi; Gouvea, Eduardo S.; Rizzo, Lucas B.; Spindola, Leticia M. N.; Honda, Pedro H. S.; Cordeiro, Quirino; Belangero, Sintia Iole; Bressan, Rodrigo Affonseca; Gadelha, Ary; Maes, Michael

    2015-01-01

    Background: There is robust evidence that schizophrenia is characterized by immune-inflammatory abnormalities, including variations on cytokine levels. The results of previous studies, however, are heterogeneous due to several confounding factors, such as the effects of antipsychotic drugs. Therefore, research on drug-naïve first-episode psychosis (FEP) patients is essential to elucidate the role of immune processes in that disorder. Methods: The aim of this study is to compare cytokine levels (IL-2, IL-10, IL-4, IL-6, IFN-γ, TNF-α, and IL-17) in drug-naïve FEP patients both before and after treatment with risperidone for 10 weeks, and to investigate possible associations between cytokine levels and clinical responses to treatment and presence of depressive symptoms. It this study, we included 55 drug-naïve FEP patients who had repeated measurements of cytokine levels and 57 healthy controls. Results: We found that FEP patients had significantly higher IL-6, IL-10 and TNF-α levels than healthy controls. After risperidone treatment, these three cytokines and additionally IL-4 decreased significantly. No significant difference was found between the post-treatment cytokine levels in FEP patients and in healthy controls, suggesting that these alterations in cytokine profiles are a state marker of FEP. No significant association was found between risperidone-induced changes in cytokines and the clinical response to treatment or the presence of depression. There was a significant inverse association between the risperidone-induced changes in IL-10 and the negative symptoms. Conclusions: In conclusion, our results show a specific cytokine profile in FEP patients (monocytic and regulatory T-cell activation) and suggest immunoregulatory effects of risperidone treatment, characterized by suppressant effects on monocytic, Th2, and T-regulatory functions. PMID:25522386

  6. Profile of male Brazilian injecting drug users who have sex with men

    Directory of Open Access Journals (Sweden)

    Ferreira Aline Dayrell

    2006-01-01

    Full Text Available This study aims to characterize the profile of male injecting drug users who have sex with other men (MSM IDUs recruited through a cross-sectional multi-city survey (AjUDE-Brasil II Project in six Brazilian cities, in 2000-2001. MSM IDUs were compared to other male IDUs using bivariate and multivariate procedures (logistic regression and answer tree analysis with the CHAID algorithm. Among the 709 male IDUs, 187 (26.4% reported ever having had sex with other men, while only 37 reported sex with other men in the previous six months. MSM IDUs were more likely to be unemployed (OR = 2.3, to have injected tranquilizers (OR = 3.6, and to be HIV-seropositive (OR = 2.1, compared to other male IDUs. Male same-sex relations in this subgroup appear to be associated with strategies to finance drug consuming habits, including sex for drugs with occasional female partners or obtaining injection paraphernalia from occasional sex partners. Further studies should focus on this especially vulnerable subgroup of IDUs, due to the bidirectional and complex interrelationships between their drug injecting habits and sexual risk behaviors.

  7. Height profile of particle concentration in an aeolian saltating cloud: A wind tunnel investigation by PIV MSD

    Science.gov (United States)

    Dong, Zhibao; Wang, Hongtao; Zhang, Xiaohang; Ayrault, Michael

    2003-10-01

    Attempt is made to define the particle concentration in an aeolian saltating cloud and its variation with height using artificial spherical quartz sand in a wind tunnel. The height profiles of the relative particle concentration in aeolian saltating cloud at three wind velocities were detected by the state of the art PIV (Particle Image Velocimetry) MSD (Mie Scattering Diffusion) technique, and converted to actual concentration based on sand transport rate and the variation with height of velocity of the saltating cloud. The particle concentration was found to decay exponentially with height and to increase with wind velocity. It decayed more rapidly when the wind velocity decreased. The volume/volume concentration in the near-surface layer was at the order of 10-4. The results obtained by PIV MSD technique were in good agreement with those derived from the sand flux and velocity profiles, the former being about 15% greater than the later.

  8. Experimental Determination of Drug Diffusion Coefficients in Unstirred Aqueous Environments by Temporally Resolved Concentration Measurements.

    Science.gov (United States)

    di Cagno, Massimiliano Pio; Clarelli, Fabrizio; Våbenø, Jon; Lesley, Christina; Rahman, Sokar Darsim; Cauzzo, Jennifer; Franceschinis, Erica; Realdon, Nicola; Stein, Paul C

    2018-04-02

    The diffusion coefficient (also known as diffusivity) of an active pharmaceutical ingredient (API) is a fundamental physicochemical parameter that affects passive diffusion through biological barriers and, as a consequence, bioavailability and biodistribution. However, this parameter is often neglected, and it is quite difficult to find diffusion coefficients of small molecules of pharmaceutical relevance in the literature. The available methods to measure diffusion coefficients of drugs all suffer from limitations that range from poor sensitivity to high selectivity of the measurements or the need for dedicated instrumentation. In this work, a simple but reliable method based on time-resolved concentration measurements by UV-visible spectroscopy in an unstirred aqueous environment was developed. This method is based on spectroscopic measurement of the variation of the local concentration of a substance during spontaneous migration of molecules, followed by standard mathematical treatment of the data in order to solve Fick's law of diffusion. This method is extremely sensitive and results in highly reproducible data. The technique was also employed to verify the influence of the environmental characteristics (i.e., ionic strength and presence of complexing agents) on the diffusivity. The method can be employed in any research laboratory equipped with a standard UV-visible spectrophotometer and could become a useful and straightforward tool in order to characterize diffusion coefficients in physiological conditions and help to better understand the drug permeability process.

  9. Artificial neural networks to evaluate the boron concentration decreasing profile in Blood-BPA samples of BNCT patients

    International Nuclear Information System (INIS)

    García-Reiriz, Alejandro; Magallanes, Jorge; Zupan, Jure; Líberman, Sara

    2011-01-01

    For the prediction of decay concentration profiles of the p-boronophenylalanine (BPA) in blood during BNCT treatment, a method is suggested based on Kohonen neural networks. The results of a model trained with the concentration profiles from the literature are described. The prediction of the model was validated by the leave-one-out method. Its robustness shows that it is mostly independent on small variations. The ability to fit retrospective experimental data shows an uncertainty lower than the two compartment model used previously. - Highlights: ► We predicted decaying concentration profiles of BPA in blood during BNCT therapy. ► Is suggested a method based on Kohonen neural networks. ► The results show that it is very robust and mostly independent of small variations. ► It has a better ability to fit retrospective experimental data. ► The model could be progressively improved by adding new data to the training matrix.

  10. The use of forensic case data in intelligence-led policing: the example of drug profiling.

    Science.gov (United States)

    Morelato, Marie; Beavis, Alison; Tahtouh, Mark; Ribaux, Olivier; Kirkbride, Paul; Roux, Claude

    2013-03-10

    To date, forensic science has predominantly focused on generating evidence for judicial proceedings. While many recognise its broader and important contribution to the initial stages of the forensic process, resources do not seem to be employed efficiently. It is often discovered retrospectively that necessary information was previously available in a database or within existing files. Such information could have been proactively used in order to solve a particular case, a number of linked cases or better understand the criminal activity as a whole. This article reviews this broader contribution of forensic science, with a particular emphasis on drug intelligence at the Australian Federal Police (AFP) in Australia. Using the AFP as a model organisation, an overview of the current situation and the contribution of physical and chemical profiling are first discussed. The situation in Europe, and in particular in Switzerland, is also presented. It is argued that a change of attitude towards a more intelligence-led perspective is required in forensic science in general, and in drug profiling in particular. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2015-01-01

    The multidrug resistant Enterococcus faecium (MEF) strains originating from farm animals are proliferating at a substantial pace to impact downstream food chains and could reach hospitals. This study was conducted to elucidate the drug susceptibility profile of MEF strains collected from poultry products in Ann Arbor, MI area and clinical settings from Michigan State Lab and Moffitt Cancer Center (MCC) in Florida. Presumptive positive Enterococcus isolates at species level were identified by Matrix Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) analysis. The antibiotic susceptibility profile for both poultry and clinical strains was determined by the Thermo Scientific's Sensititre conform to the National Committee for Clinical Laboratory Standards (NCCLS) and validated via quantitative real-time PCR (qPCR) methods. Out of 50 poultry samples (Turkey: n = 30; Chicken: n = 20), 36 samples were positive for Enterococcus species from which 20.83% were identified as E. faecium. All the E. faecium isolates were multidrug resistant and displayed resistance to the last alternative drug, quinupristin/dalfopristin (QD) used to treat vancomycin resistant E. faecium (VRE) in hospitals. Results indicate the presence of MEF strains in food animals and clinical settings that are also resistant to QD.

  12. User characteristics and effect profile of Butane Hash Oil: An extremely high-potency cannabis concentrate.

    Science.gov (United States)

    Chan, Gary C K; Hall, Wayne; Freeman, Tom P; Ferris, Jason; Kelly, Adrian B; Winstock, Adam

    2017-09-01

    Recent reports suggest an increase in use of extremely potent cannabis concentrates such as Butane Hash Oil (BHO) in some developed countries. The aims of this study were to examine the characteristics of BHO users and the effect profiles of BHO. Anonymous online survey in over 20 countries in 2014 and 2015. Participants aged 18 years or older were recruited through onward promotion and online social networks. The overall sample size was 181,870. In this sample, 46% (N=83,867) reported using some form of cannabis in the past year, and 3% reported BHO use (n=5922). Participants reported their use of 7 types of cannabis in the past 12 months, the source of their cannabis, reasons for use, use of other illegal substances, and lifetime diagnosis for depression, anxiety and psychosis. Participants were asked to rate subjective effects of BHO and high potency herbal cannabis. Participants who reported a lifetime diagnosis of depression (OR=1.15, p=0.003), anxiety (OR=1.72, pcannabis. BHO users also reported stronger negative effects and less positive effects when using BHO than high potency herbal cannabis (pcannabis. Copyright © 2017. Published by Elsevier B.V.

  13. Quantification and Analysis of Suspended Sediments Concentration Using Mobile and Static Acoustic Doppler Current Profiler Instruments

    Directory of Open Access Journals (Sweden)

    Angga Dwinovantyo

    2017-01-01

    Full Text Available The application of Acoustic Doppler Current Profiler (ADCP can be used not only for measuring ocean currents, but also for quantifying suspended sediment concentrations (SSC from acoustic backscatter strength based on sonar principle. Suspended sediment has long been recognized as the largest sources of sea contaminant and must be considered as one of the important parameters in water quality of seawater. This research was to determine SSC from measured acoustic backscattered intensity of static and mobile ADCP. In this study, vertically mounted 400 kHz and 750 kHz static ADCP were deployed in Lembeh Strait, North Sulawesi. A mobile ADCP 307.2 kHz was also mounted on the boat and moved to the predefined cross-section, accordingly. The linear regression analysis of echo intensity measured by ADCP and by direct measurement methods showed that ADCP is a reliable method to measure SSC with correlation coefficient (r 0.92. Higher SSC was observed in low water compared to that in high water and near port area compared to those in observed areas. All of this analysis showed that the combination of static and mobile ADCP methods produces reasonably good spatial and temporal data of SSC.

  14. A Generic Multi-Compartmental CNS Distribution Model Structure for 9 Drugs Allows Prediction of Human Brain Target Site Concentrations

    NARCIS (Netherlands)

    Yamamoto, Yumi; Valitalo, Pyry A.; van den Berg, Dirk-Jan; Hartman, Robin; van den Brink, Willem; Wong, Yin Cheong; Huntjens, Dymphy R.; Proost, Johannes H.; Vermeulen, An; Krauwinkel, Walter; Bakshi, Suruchi; Aranzana-Climent, Vincent; Marchand, Sandrine; Dahyot-Fizelier, Claire; Couet, William; Danhof, Meindert; van Hasselt, Johan G. C.; de lange, Elizabeth C. M.

    Purpose Predicting target site drug concentration in the brain is of key importance for the successful development of drugs acting on the central nervous system. We propose a generic mathematical model to describe the pharmacokinetics in brain compartments, and apply this model to predict human

  15. Proteomic profiling of the antifungal drug response of Aspergillus fumigatus to voriconazole.

    Science.gov (United States)

    Amarsaikhan, Nansalmaa; Albrecht-Eckardt, Daniela; Sasse, Christoph; Braus, Gerhard H; Ogel, Zumrut B; Kniemeyer, Olaf

    2017-10-01

    Antifungal resistance is an emerging problem and one of the reasons for treatment failure of invasive aspergillosis (IA). Voriconazole has become a standard therapeutic for the treatment of this often fatal infection. We studied the differentially expressed proteins as a response of Aspergillus fumigatus to voriconazole by employing the two-dimensional difference gel electrophoresis (DIGE) technique. Due to addition of drug, a total of 135 differentially synthesized proteins were identified by MALDI-TOF/TOF-mass spectrometry. In particular, the level of proteins involved in the general stress response and cell detoxification increased prominently. In contrast, cell metabolism and energy proteins were down-regulated, which suggests the cellular effort to maintain balance in energy utilization while trying to combat the cellular stress exerted by the drug. We detected several so-far uncharacterized proteins which may play a role in stress response and drug metabolism and which could be future targets for antifungal treatment. A mutant strain, which is deleted in the cross-pathway control gene cpcA, was treated with voriconazole to investigate the contribution of the general control of amino acid biosynthesis to drug resistance. We compared the mutant strain's protein expression profile with the wild-type strain. The absence of CpcA led to an increased resistance to voriconazole and a reduced activation of some general stress response proteins, while the transcript level of the triazole target gene erg11A (cyp51A) remained unchanged. In contrast, the sensitivity of strain ΔcpcA to terbinafine and amphotericin B was slightly increased. These findings imply a role of CpcA in the cellular stress response to azole drugs at the post transcriptional level. Copyright © 2017 Elsevier GmbH. All rights reserved.

  16. Transcriptional profiling of the dose response: a more powerful approach for characterizing drug activities.

    Directory of Open Access Journals (Sweden)

    Rui-Ru Ji

    2009-09-01

    Full Text Available The dose response curve is the gold standard for measuring the effect of a drug treatment, but is rarely used in genomic scale transcriptional profiling due to perceived obstacles of cost and analysis. One barrier to examining transcriptional dose responses is that existing methods for microarray data analysis can identify patterns, but provide no quantitative pharmacological information. We developed analytical methods that identify transcripts responsive to dose, calculate classical pharmacological parameters such as the EC50, and enable an in-depth analysis of coordinated dose-dependent treatment effects. The approach was applied to a transcriptional profiling study that evaluated four kinase inhibitors (imatinib, nilotinib, dasatinib and PD0325901 across a six-logarithm dose range, using 12 arrays per compound. The transcript responses proved a powerful means to characterize and compare the compounds: the distribution of EC50 values for the transcriptome was linked to specific targets, dose-dependent effects on cellular processes were identified using automated pathway analysis, and a connection was seen between EC50s in standard cellular assays and transcriptional EC50s. Our approach greatly enriches the information that can be obtained from standard transcriptional profiling technology. Moreover, these methods are automated, robust to non-optimized assays, and could be applied to other sources of quantitative data.

  17. Effect of whey protein concentrate and sodium chloride concentrations on the odour profile of sous vide cooked whole-muscle beef from Argentina.

    Science.gov (United States)

    Grigioni, G; Langman, L; Szerman, N; Irurueta, M; Vaudagna, S R

    2008-07-01

    Semitendinosus muscles added with whey protein concentrate (WPC) and sodium chloride (NaCl) were submitted to sous vide cooking. Four enhancement treatments and a control were tested: 0.875% WPC (w/w)+0.625% NaCl, 2.625% WPC+0.625% NaCl, 0.875% WPC+1.875% NaCl, 2.625% WPC+1.875% NaCl, and control (non-injected muscles). Odour analyses were carried out with an electronic nose (EN) system. EN data were evaluated applying Principal Component Analysis, Linear Discriminant Analysis and Partial Least Squares algorithm. EN was able to discriminate the odour profiles of cooked enhanced beef as a function of the amount of WPC added. No significant differences in odour profiles were observed regarding NaCl concentration. These results agreed with those obtained when odour profiles were analysed in WPC dispersions. The reported results support the applicability of EN methodology for analysing the impact of processing parameters on beef odour profiles.

  18. Wastewater-based epidemiology and enantiomeric profiling for drugs of abuse in South African wastewaters.

    Science.gov (United States)

    Archer, E; Castrignanò, E; Kasprzyk-Hordern, B; Wolfaardt, G M

    2018-06-01

    The current study is aimed to introduce a wastewater-based epidemiology (WBE) approach for the first time on the African continent where substance abuse data is limited. The study included the quantification of several drugs of abuse (DOA) in raw wastewater samples. Quantification of urinary metabolites as drug target residues (DTR), as well as enantiomeric profiling of chiral DOA was performed to distinguish between consumption and direct disposal into sewage. Monitoring campaigns were undertaken at two South African wastewater treatment works (WWTWs) located within two provinces of the country. The presence of non-racemic 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine, as well as the metabolite of cocaine, benzoylecgonine (BEG), confirmed their consumption within the areas investigated. Enantiomeric profiling further pointed to the abuse of methamphetamine as the primary DOA with use estimates calculated between 181.9 and 1184.8mg·day -1 ·1000inhabitants -1 . Population-normalised mass loads for MDMA and cocaine confirmed their status as secondary DOA within the study sites. Use estimates for the new psychoactive substance (NPS) mephedrone were performed for one WWTW. The minor metabolite of heroin, O-6-monoacetylmorphine (O-6-MAM), was also detected at one WWTW and served as a qualitative indicator for heroin abuse within the area. These findings provide a novel comparison of the WBE approach in a developing-country with other global studies, with the aim to strengthen this approach as a tool to inform drug prevention strategies in countries where substance abuse data is limited due to financial constraints and lack of government structures to facilitate conventional monitoring. Copyright © 2017. Published by Elsevier B.V.

  19. A self-assembled nanocarrier loading teniposide improves the oral delivery and drug concentration in tumor.

    Science.gov (United States)

    Zhang, Zhiwen; Ma, Li; Jiang, Shijun; Liu, Zeying; Huang, Jian; Chen, Lingli; Yu, Haijun; Li, Yaping

    2013-02-28

    We attempted to improve the oral delivery of lipophilic teniposide to achieve higher drug concentration in tumor by self-assembled nanocarrier for further oral chemotherapy. The teniposide loaded self-assembled nanocarrier (TSN) was spherical nanometric particles with narrow size distribution. The intestinal absorption of teniposide from TSN was obviously improved 4.09- and 6.35-fold in duodenum and jejunum at 0.5h after oral administration, then significantly decreased with the prolongation of time. The cellular uptake of TSN in Caco-2 cell monolayer was significantly enhanced over 3 folds and increased with incubation time. Moreover, TSN could be internalized into Caco-2 cell monolayer through clathrin-mediated endocytosis pathway, and then mainly transported into the systemic circulation via portal vein and intestinal lymphatic pathway. The pharmacokinetic results indicated that the AUC(0-t) value of TSN in rats was significantly improved 5.41-fold than that of teniposide solution, moreover, the teniposide concentration in tumor from TSN was obviously improved over 7-fold in tumor bearing mice. The captured image indicated that the oral administered TSN could specifically accumulate in tumor in the xenograft model. Therefore, the self-assembled nanocarrier was promising to enhance the oral delivery of lipophilic teniposide and its concentration in tumor for oral chemotherapy. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Pharmacokinetic drug interaction profile of omeprazole with adverse consequences and clinical risk management

    Directory of Open Access Journals (Sweden)

    Li W

    2013-05-01

    Full Text Available Wei Li,1 Su Zeng,2 Lu-Shan Yu,2 Quan Zhou31Division of Medical Affairs, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People’s Republic of China; 3Department of Pharmacy, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of ChinaBackground: Omeprazole, a proton pump inhibitor (PPI, is widely used for the treatment of dyspepsia, peptic ulcer, gastroesophageal reflux disease, and functional dyspepsia. Polypharmacy is common in patients receiving omeprazole. Drug toxicity and treatment failure resulting from inappropriate combination therapy with omeprazole have been reported sporadically. Systematic review has not been available to address the pharmacokinetic drug-drug interaction (DDI profile of omeprazole with adverse consequences, the factors determining the degree of DDI between omeprazole and comedication, and the corresponding clinical risk management.Methods: Literature was identified by performing a PubMed search covering the period from January 1988 to March 2013. The full text of each article was critically reviewed, and data interpretation was performed.Results: Omeprazole has actual adverse influences on the pharmacokinetics of medications such as diazepam, carbamazepine, clozapine, indinavir, nelfinavir, atazanavir, rilpivirine, methotrexate, tacrolimus, mycophenolate mofetil, clopidogrel, digoxin, itraconazole, posaconazole, and oral iron supplementation. Meanwhile, low efficacy of omeprazole treatment would be anticipated, as omeprazole elimination could be significantly induced by comedicated efavirenz and herb medicines such as St John's wort, Ginkgo biloba, and yin zhi huang. The mechanism for DDI involves induction or inhibition of cytochrome P450, inhibition of P-glycoprotein or breast

  1. [Analysis of voriconazole serum concentrations and safety profile in pediatric oncology patients].

    Science.gov (United States)

    Silva, Felipe; Navea, Daniel; Saias, Carolina; Torres, Juan P; Catalán, Paula; Morales, Jorge

    2016-04-01

    Voriconazole (VCZ) serum drug levels (SDL) vary widely and are associated with increased mortality when they are below the therapeutic range for invasive aspergillosis (IA). To describe VCZ SDL in oncology pediatric patients in order to reach adequate concentrations for prophylaxis (≥ 0.5 mg/L) and treatment (≥ 1.0 y 2.0 mg/L) for IA and their relationship with toxicity. Retrospective analysis of VCZ SDL and toxicities recorded in oncology pediatric patients between February 2013 and November 2014. The daily dosage and SDLs were analyzed according to administration route: intravenous (IV) and oral (PO), type of therapy (prophylaxis and treatment) and patient age (patients were analyzed and the average age was 9.3 years-old. The SDL obtained from the IV route were 43.7%. There were more SDL ≥ 0.5 mg/L and ≥ 1.0 mg/L with the IV route than the PO route (p Patients younger than 12-years-old received a higher dosage than those ≥ 12 years old (median 18.6 and 9.2 mg/kg/d, respectively, p patients (80-100% SDL ≥ 0.5 mg/L). With an IV dosage between 14 and 20 mg/kg/day in patients > 12-years-old, 80% of the SDL were ≥ 1 mg/L and ≥ 2 mg/L. In patients younger than 12-year-old, dosages between 8-30 mg/ kg/day showed similar results (50-63% of SDL ≥ 1 mg/L and 36-40% of SDL ≥ 2 mg/L). Eight patients (30.8%) presented an adverse drug reaction and no relationship with the SDL was found. Conclusión: A VCZ standard dosage of 200 mg every 12 hours PO showed the best results for IA prophylaxis in all patients. Patients younger than 12-years-old would require higher dosages than the doses used in this study to attain adequate SDL for IA treatment. No relation with SDL and adverse reactions was found.

  2. Plasma Drug Concentrations of Orally Administered Rosuvastatin in Hispaniolan Amazon Parrots (Amazona ventralis).

    Science.gov (United States)

    Beaufrère, Hugues; Papich, Mark G; Brandão, João; Nevarez, Javier; Tully, Thomas N

    2015-03-01

    Atherosclerotic diseases are common in pet psittacine birds, in particular Amazon parrots. While hypercholesterolemia and dyslipidemia have not definitely been associated with increased susceptibility to atherosclerosis in parrots, these are important and well-known risk factors in humans. Therefore statin drugs such as rosuvastatin constitute the mainstay of human treatment of dyslipidemia and the prevention of atherosclerosis. No pharmacologic studies have been performed in psittacine birds despite the high prevalence of atherosclerosis in captivity. Thirteen Hispaniolan Amazon parrots were used to test a single oral dose of 10 mg/kg of rosuvastatin with blood sampling performed according to a balanced incomplete block design over 36 hours. Because low plasma concentrations were produced in the first study, a subsequent pilot study using a dose of 25 mg/kg in 2 Amazon parrots was performed. Most plasma samples for the 10 mg/kg dose and all samples for the 25 mg/kg dose had rosuvastatin concentration below the limits of quantitation. For the 10 mg/kg study, the median peak plasma concentration and time to peak plasma concentration were 0.032 μg/mL and 2 hours, respectively. Our results indicate that rosuvastatin does not appear suitable in Amazon parrots as compounded and used at the dose in this study. Pharmacodynamic studies investigating lipid-lowering effects of statins rather than pharmacokinetic studies may be more practical and cost effective in future studies to screen for a statin with more ideal properties for potential use in psittacine dyslipidemia and atherosclerotic diseases.

  3. Feeding low or pharmacological concentrations of zinc oxide changes the hepatic proteome profiles in weaned piglets.

    Directory of Open Access Journals (Sweden)

    Angelika Bondzio

    Full Text Available Pharmacological levels of zinc oxide can promote growth and health of weaning piglets, but the underlying molecular mechanisms are yet not fully understood. The aim of this study was to determine changes in the global hepatic protein expression in response to dietary zinc oxide in weaned piglets. Nine half-sib piglets were allocated to three dietary zinc treatment groups (50, 150, 2500 mg/kg dry matter. After 14 d, pigs were euthanized and liver samples taken. The increase in hepatic zinc concentration following dietary supplementation of zinc was accompanied by up-regulation of metallothionein mRNA and protein expression. Global hepatic protein profiles were obtained by two-dimensional difference gel electrophoresis following matrix-assisted laser desorption ionization/time-of-flight mass spectrometry. A total of 15 proteins were differentially (P<0.05 expressed between groups receiving control (150 mg/kg or pharmacological levels of zinc (2500 mg/kg with 7 down- (e.g. arginase1, thiosulfate sulfurtransferase, HSP70 and 8 up-regulated (e.g. apolipoprotein AI, transferrin, C1-tetrahydrofolate synthase proteins. Additionally, three proteins were differentially expressed with low zinc supply (50 mg/kg Zn in comparison to the control diet. The identified proteins were mainly associated with functions related to cellular stress, transport, metabolism, and signal transduction. The differential regulation was evaluated at the mRNA level and a subset of three proteins of different functional groups was selected for confirmation by western blotting. The results of this proteomic study suggest that zinc affects important liver functions such as blood protein secretion, protein metabolism, detoxification and redox homeostasis, thus supporting the hypothesis of intermediary effects of pharmacological levels of zinc oxide fed to pigs.

  4. In situ quantitative measurement of concentration profiles in a microreactor with submicron resolution using multiplex CARS microscopy

    NARCIS (Netherlands)

    Schafer, D.; Squier, J.A.; van Maarseveen, J.; Bonn, D.; Bonn, M.; Müller, M.

    2008-01-01

    In situ quantitative imaging of concentration profiles of reactants and products inside a microfluidic reactor is achieved, with submicron spatial resolution with similar to mM sensitivity and on similar to ms time scales, for a given position. The label-free approach relies on quantitative

  5. Load Concentration Factor Based Analytical Method for Optimal Placement of Multiple Distribution Generators for Loss Minimization and Voltage Profile Improvement

    NARCIS (Netherlands)

    Shahzad, Mohsin; Ahmad, Ishtiaq; Gawlik, Wolfgang; Palensky, P.

    2016-01-01

    This paper presents novel separate methods for finding optimal locations, sizes of multiple distributed generators (DGs) simultaneously and operational power factor in order to minimize power loss and improve the voltage profile in the distribution system. A load concentration factor (LCF) is

  6. Functional profiling of microtumors to identify cancer associated fibroblast-derived drug targets.

    Science.gov (United States)

    Horman, Shane R; To, Jeremy; Lamb, John; Zoll, Jocelyn H; Leonetti, Nicole; Tu, Buu; Moran, Rita; Newlin, Robbin; Walker, John R; Orth, Anthony P

    2017-11-21

    Recent advances in chemotherapeutics highlight the importance of molecularly-targeted perturbagens. Although these therapies typically address dysregulated cancer cell proteins, there are increasing therapeutic modalities that take into consideration cancer cell-extrinsic factors. Targeting components of tumor stroma such as vascular or immune cells has been shown to represent an efficacious approach in cancer treatment. Cancer-associated fibroblasts (CAFs) exemplify an important stromal component that can be exploited in targeted therapeutics, though their employment in drug discovery campaigns has been relatively minimal due to technical logistics in assaying for CAF-tumor interactions. Here we report a 3-dimensional multi-culture tumor:CAF spheroid phenotypic screening platform that can be applied to high-content drug discovery initiatives. Using a functional genomics approach we systematically profiled 1,024 candidate genes for CAF-intrinsic anti-spheroid activity; identifying several CAF genes important for development and maintenance of tumor:CAF co-culture spheroids. Along with previously reported genes such as WNT, we identify CAF-derived targets such as ARAF and COL3A1 upon which the tumor compartment depends for spheroid development. Specifically, we highlight the G-protein-coupled receptor OGR1 as a unique CAF-specific protein that may represent an attractive drug target for treating colorectal cancer. In vivo , murine colon tumor implants in OGR1 knockout mice displayed delayed tumor growth compared to tumors implanted in wild type littermate controls. These findings demonstrate a robust microphysiological screening approach for identifying new CAF targets that may be applied to drug discovery efforts.

  7. Plutonium, americium, and uranium concentrations in Nevada Test Site soil profiles

    International Nuclear Information System (INIS)

    Essington, E.H.; Gilbert, R.O.; Eberhardt, L.L.; Fowler, E.B.

    1975-01-01

    Many soil profile samples were collected by the Nevada Applied Ecology Group from five nuclear safety test sites on the Nevada Test Site and Tonopah Test Range in Nevada, U.S.A. The profile samples were analyzed for 239 Pu, 240 Pu, 241 Am, and in some cases 235 U and 238 U, in order to estimate the depth of radionuclide penetration and level of contamination at specific sampling depths after an extended period of time since deposition on the surface. Nearly 70 individual profiles were examined. About one-half of the profiles exhibited a smooth leaching pattern with more than 95 percent of the plutonium in the top 5 cm. Other profile patterns are discussed relative to mechanical disturbance of the profile after the initial deposition, accumulation of plutonium in specific zones within the soil profile, and occurrence of large amounts of plutonium in the deepest parts of the soil profile. The implications of these observations are discussed with respect to redistribution of radioactivity by wind, water, and burrowing animals, ingestion by burrowing and grazing animals, uptake by vegetation, and cleanup operations. (auth)

  8. Determination of rare earth elements concentration at different depth profile of Precambrian pegmatites using instrumental neutron activation analysis.

    Science.gov (United States)

    Sadiq Aliyu, Abubakar; Musa, Yahaya; Liman, M S; Abba, Habu T; Chaanda, Mohammed S; Ngene, Nnamani C; Garba, N N

    2018-01-01

    The Keffi area hosts abundant pegmatite bodies as a result of the surrounding granitic intrusions. Keffi is part of areas that are geologically classified as North Central Basement Complex. Data on the mineralogy and mineralogical zonation of the Keffi pegmatite are scanty. Hence the need to understand the geology and mineralogical zonation of Keffi pegmatites especially at different depth profiles is relevant as a study of the elemental composition of the pegmatite is essential for the estimation of its economic viability. Here, the relative standardization method of instrumental neutron activation analysis (INAA) has been used to investigate the vertical deviations of the elemental concentrations of rare earth elements (REEs) at different depth profile of Keffi pegmatite. This study adopted the following metrics in investigating the vertical variations of REEs concentrations. Namely, the total contents of rare earth elements (∑REE); ratio of light to heavy rare earth elements (LREE/HREE), which defines the enrichment or depletion of REEs; europium anomaly (Eu/Sm); La/Lu ratio relative to chondritic meteorites. The study showed no significant variations in the total content of rare elements between the vertical depth profiles (100-250m). However, higher total concentrations of REEs (~ 92.65ppm) were recorded at the upper depth of the pegmatite and the europium anomaly was consistently negative at all the depth profiles suggesting that the Keffi pegmatite is enriched with light REEs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Studying the personality profile of drug addicts by utilizing two models of Cloninger and Eysneck

    Directory of Open Access Journals (Sweden)

    2008-11-01

    Full Text Available Objectives: Identifying personality factors of tendency to drugs can be helpful in better recognition and treatment of drug-dependency and also by providing consulting and psychological services can relatively prevents from vulnerable people to be addicted. This research therefore aims to investigate personality profile of substance dependent by using personality models of Cloninger and Eysenck. Methods: 100 substance-dependent and 100 normal men selected by available sampling method and completed Temperament and Character Inventory of Cloninger (TCI and Eysenck Personality Questionnaire _ Revised (EPQ-R. Also, some democratic information regarding substance- dependents collected. Research data were analyzed by inferential and descriptive statistics. Findings: This research showed that there are significant differences in temperament dimensions of novelty seeking and harm avoidance and character dimensions of self-direction and cooperativeness of Cloninger model and neuroticism and psychosis dimensions of Eysenck model between substance- dependent men and normal men. Results: Comparing in normal men, substance dependent men gained higher scores at novelty seeking and neuroticism and psychosis, and lower scores at self-direction and cooperativeness.

  10. Correlates of Sex Trading among Drug-Involved Women in Committed Intimate Relationships: A Risk Profile.

    Science.gov (United States)

    Jiwatram-Negrón, Tina; El-Bassel, Nabila

    2015-01-01

    Despite a slight decline in new human immunodeficiency virus (HIV) infections in New York, marked increases and concentrated epidemics continue among subsets of the population, including women engaged in sex trading. We examined the prevalence and correlates of sex trading among 346 low-income, HIV-negative women in HIV-concordant intimate relationships. Women and their long-term main partners were recruited to participate in an HIV prevention intervention. Baseline data were used in this article. Of the 346 women in the study, 28% reported sex trading during the prior 90 days. Multivariate analyses showed increased relative risk of sex trading by lifetime experience of severe intimate partner violence (IPV), drug, and alcohol use, and marginal significance for mental health hospitalization, partner drug dependency, and homelessness. These findings suggest an urgent need for HIV prevention and intervention efforts targeted toward women in intimate relationships who trade sex for money or drugs, with an emphasis on IPV, mental health, history of incarceration, and substance abuse. Copyright © 2015 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

  11. Oxygen 18 concentration profile measurements near the surface by 18O(p,α)15N resonance reaction

    International Nuclear Information System (INIS)

    Amsel, G.; David, D.

    1975-01-01

    The method of spectrum reduction in nuclear reaction microanalysis does not allow to obtain depth resolutions better than the order of 2000A. Resolutions of the order of 200A may be obtained by using the narrow resonance technique, when applied to thin films. The latter technique was extended to thick targets, with deep concentration profiles presenting a sharp gradient near the surface. This method is presented and illustrated by the study of 18 O profiles in oxygen diffusion measurements in growing ZrO 2 , using the 629keV resonance of the reaction 18 O(p,α) 15 N [fr

  12. Profile of drug administration errors in anesthesia among anesthesiologists from Santa Catarina

    Directory of Open Access Journals (Sweden)

    Thomas Rolf Erdmann

    2016-02-01

    Full Text Available INTRODUCTION: Anesthesiology is the only medical specialty that prescribes, dilutes, and administers drugs without conferral by another professional. Adding to the high frequency of drug administration, a propitious scenario to errors is created. OBJECTIVE: Access the prevalence of drug administration errors during anesthesia among anesthesiologists from Santa Catarina, the circumstances in which they occurred, and possible associated factors. MATERIALS AND METHODS: An electronic questionnaire was sent to all anesthesiologists from Sociedade de Anestesiologia do Estado de Santa Catarina, with direct or multiple choice questions on responder demographics and anesthesia practice profile; prevalence of errors, type and consequence of error; and factors that may have contributed to the errors. RESULTS: Of the respondents, 91.8% reported they had committed administration errors, adding the total error of 274 and mean of 4.7 (6.9 errors per respondent. The most common error was replacement (68.4%, followed by dose error (49.1%, and omission (35%. Only 7% of respondents reported neuraxial administration error. Regarding circumstances of errors, they mainly occurred in the morning (32.7%, in anesthesia maintenance (49%, with 47.8% without harm to the patient and 1.75% with the highest morbidity and irreversible damage, and 87.3% of cases with immediate identification. As for possible contributing factors, the most frequent were distraction and fatigue (64.9% and misreading of labels, ampoules, or syringes (54.4%. CONCLUSION: Most respondents committed more than one error in anesthesia administration, mainly justified as a distraction or fatigue, and of low gravity.

  13. [Profile of drug administration errors in anesthesia among anesthesiologists from Santa Catarina].

    Science.gov (United States)

    Erdmann, Thomas Rolf; Garcia, Jorge Hamilton Soares; Loureiro, Marcos Lázaro; Monteiro, Marcelo Petruccelli; Brunharo, Guilherme Muriano

    2016-01-01

    Anesthesiology is the only medical specialty that prescribes, dilutes, and administers drugs without conferral by another professional. Adding to the high frequency of drug administration, a propitious scenario to errors is created. Access the prevalence of drug administration errors during anesthesia among anesthesiologists from Santa Catarina, the circumstances in which they occurred, and possible associated factors. An electronic questionnaire was sent to all anesthesiologists from Sociedade de Anestesiologia do Estado de Santa Catarina, with direct or multiple choice questions on responder demographics and anesthesia practice profile; prevalence of errors, type and consequence of error; and factors that may have contributed to the errors. Of the respondents, 91.8% reported they had committed administration errors, adding the total error of 274 and mean of 4.7 (6.9) errors per respondent. The most common error was replacement (68.4%), followed by dose error (49.1%), and omission (35%). Only 7% of respondents reported neuraxial administration error. Regarding circumstances of errors, they mainly occurred in the morning (32.7%), in anesthesia maintenance (49%), with 47.8% without harm to the patient and 1.75% with the highest morbidity and irreversible damage, and 87.3% of cases with immediate identification. As for possible contributing factors, the most frequent were: distraction and fatigue (64.9%) and misreading of labels, ampoules, or syringes (54.4%). Most respondents committed more than one error in anesthesia administration, mainly justified as a distraction or fatigue, and of low gravity. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  14. Profile of drug administration errors in anesthesia among anesthesiologists from Santa Catarina.

    Science.gov (United States)

    Erdmann, Thomas Rolf; Garcia, Jorge Hamilton Soares; Loureiro, Marcos Lázaro; Monteiro, Marcelo Petruccelli; Brunharo, Guilherme Muriano

    2016-01-01

    Anesthesiology is the only medical specialty that prescribes, dilutes, and administers drugs without conferral by another professional. Adding to the high frequency of drug administration, a propitious scenario to errors is created. Access the prevalence of drug administration errors during anesthesia among anesthesiologists from Santa Catarina, the circumstances in which they occurred, and possible associated factors. An electronic questionnaire was sent to all anesthesiologists from Sociedade de Anestesiologia do Estado de Santa Catarina, with direct or multiple choice questions on responder demographics and anesthesia practice profile; prevalence of errors, type and consequence of error; and factors that may have contributed to the errors. Of the respondents, 91.8% reported they had committed administration errors, adding the total error of 274 and mean of 4.7 (6.9) errors per respondent. The most common error was replacement (68.4%), followed by dose error (49.1%), and omission (35%). Only 7% of respondents reported neuraxial administration error. Regarding circumstances of errors, they mainly occurred in the morning (32.7%), in anesthesia maintenance (49%), with 47.8% without harm to the patient and 1.75% with the highest morbidity and irreversible damage, and 87.3% of cases with immediate identification. As for possible contributing factors, the most frequent were distraction and fatigue (64.9%) and misreading of labels, ampoules, or syringes (54.4%). Most respondents committed more than one error in anesthesia administration, mainly justified as a distraction or fatigue, and of low gravity. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  15. Quantitatively integrating molecular structure and bioactivity profile evidence into drug-target relationship analysis

    Directory of Open Access Journals (Sweden)

    Xu Tianlei

    2012-05-01

    Full Text Available Abstract Background Public resources of chemical compound are in a rapid growth both in quantity and the types of data-representation. To comprehensively understand the relationship between the intrinsic features of chemical compounds and protein targets is an essential task to evaluate potential protein-binding function for virtual drug screening. In previous studies, correlations were proposed between bioactivity profiles and target networks, especially when chemical structures were similar. With the lack of effective quantitative methods to uncover such correlation, it is demanding and necessary for us to integrate the information from multiple data sources to produce an comprehensive assessment of the similarity between small molecules, as well as quantitatively uncover the relationship between compounds and their targets by such integrated schema. Results In this study a multi-view based clustering algorithm was introduced to quantitatively integrate compound similarity from both bioactivity profiles and structural fingerprints. Firstly, a hierarchy clustering was performed with the fused similarity on 37 compounds curated from PubChem. Compared to clustering in a single view, the overall common target number within fused classes has been improved by using the integrated similarity, which indicated that the present multi-view based clustering is more efficient by successfully identifying clusters with its members sharing more number of common targets. Analysis in certain classes reveals that mutual complement of the two views for compound description helps to discover missing similar compound when only single view was applied. Then, a large-scale drug virtual screen was performed on 1267 compounds curated from Connectivity Map (CMap dataset based on the fused similarity, which obtained a better ranking result compared to that of single-view. These comprehensive tests indicated that by combining different data representations; an improved

  16. Drug Concentration Thresholds Predictive of Therapy Failure and Death in Children With Tuberculosis: Bread Crumb Trails in Random Forests.

    Science.gov (United States)

    Swaminathan, Soumya; Pasipanodya, Jotam G; Ramachandran, Geetha; Hemanth Kumar, A K; Srivastava, Shashikant; Deshpande, Devyani; Nuermberger, Eric; Gumbo, Tawanda

    2016-11-01

     The role of drug concentrations in clinical outcomes in children with tuberculosis is unclear. Target concentrations for dose optimization are unknown.  Plasma drug concentrations measured in Indian children with tuberculosis were modeled using compartmental pharmacokinetic analyses. The children were followed until end of therapy to ascertain therapy failure or death. An ensemble of artificial intelligence algorithms, including random forests, was used to identify predictors of clinical outcome from among 30 clinical, laboratory, and pharmacokinetic variables.  Among the 143 children with known outcomes, there was high between-child variability of isoniazid, rifampin, and pyrazinamide concentrations: 110 (77%) completed therapy, 24 (17%) failed therapy, and 9 (6%) died. The main predictors of therapy failure or death were a pyrazinamide peak concentration children children with tuberculosis. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  17. Longitudinal community plasma HIV-1 RNA concentrations and incidence of HIV-1 among injecting drug users: prospective cohort study

    OpenAIRE

    Wood, Evan; Kerr, Thomas; Marshall, Brandon D L; Li, Kathy; Zhang, Ruth; Hogg, Robert S; Harrigan, P Richard; Montaner, Julio S G

    2009-01-01

    Objective To examine the relation between plasma HIV-1 RNA concentrations in the community and HIV incidence among injecting drug users. Design Prospective cohort study. Setting Inner city community in Vancouver, Canada. Participants Injecting drug users, with and without HIV, followed up every six months between 1 May 1996 and 30 June 2007. Main outcome measures Estimated community plasma HIV-1 RNA in the six months before each HIV negative participant?s follow-up visit. Associated HIV incid...

  18. Commercial viability of CNS drugs: balancing the risk/reward profile.

    Science.gov (United States)

    Johnson, Ginger S

    2014-01-01

    CNS has historically been a formidable therapeutic area in which to innovate owing to biological (e.g., complex neurobiology, difficulty reaching the target), as well as clinical (e.g., subjective clinical endpoints, high placebo response, lack of biomarkers) challenges. In the current market where many of the larger diseases are dominated by a generic standard of care, commercial challenges now make the triple threat of scientific-clinical-commercial risk too much for many players to tackle. However, opportunities do exist for smaller biotech companies to concentrate on narrowly focused patient populations associated with high unmet need for which risk can be tightly defined. In CNS, there are two major areas to balance the risk/reward profile and create commercially viable opportunities: To realize value, all companies (start-ups and big players) must define, measure and quantify clear and meaningful value to all stakeholders: physicians, patients, caregivers and payers. © 2013.

  19. Mg concentration profile and its control in the low temperature grown Mg-doped GaN epilayer

    Science.gov (United States)

    Liu, S. T.; Yang, J.; Zhao, D. G.; Jiang, D. S.; Liang, F.; Chen, P.; Zhu, J. J.; Liu, Z. S.; Liu, W.; Xing, Y.; Zhang, L. Q.; Wang, W. J.; Li, M.; Zhang, Y. T.; Du, G. T.

    2018-01-01

    In this work, the Cp2Mg flux and growth pressure influence to Mg doping concentration and depth profiles is studied. From the SIMS measurement we found that a transition layer exists at the bottom region of the layer in which the Mg doping concentration changes gradually. The thickness of transition layer decreases with the increases of Mg doping concentration. Through analysis, we found that this is caused by Ga memory effect which the Ga atoms stay residual in MOCVD system will react with Mg source, leading a transition layer formation and improve the growth rate. And the Ga memory effect can be well suppressed by increasing Mg doping concentration and growth pressure and thus get a steep Mg doping at the bottom region of p type layer.

  20. Inventories and concentration profiles of 137Cs in undisturbed soils in the northeast of Buenos Aires Province, Argentina

    International Nuclear Information System (INIS)

    Montes, M.L.; Silva, L.M.S.; Sá, C.S.A.; Runco, J.; Taylor, M.A.; Desimoni, J.

    2013-01-01

    Inventories and vertical distribution of 137 Cs were determined in La Plata region undisturbed soils, Argentina. A mean inventory value of 891 ± 220 Bq/m 2 was established, which is compatible with the values expected from atmospheric weapon tests fallout. The study was complemented with pH, organic carbon fraction, texture and mineralogical soil analyses. Putting together Southern Hemisphere 137 Cs inventory data, it is possible to correlate these data with the mean annual precipitations. The large differences in 137 Cs concentration profiles were attributed to soil properties, especially the clay content and the pH values. A convection–dispersion model with irreversible retention was used to fit the activity concentration profiles. The obtained effective diffusion coefficient and effective convection velocity parameters values were in the range from 0.2 cm 2 /y to 0.4 cm 2 /y and from 0.23 cm/y to 0.43 cm/y, respectively. These data are in agreement with values reported in literature. In general, with the growth of clay content in the soil, there was an increase in the transfer rate from free to bound state. Finally, the highest transfer rate from free to bound state was obtained for soil pH value equal to 8. - Highlights: ► Inventories and vertical distribution of 137 Cs were determined in undisturbed soils of La Plata city region, Argentina. ► The study was complemented with soil analyses of pH, organic carbon, texture and mineralogy. ► Inventory data were correlated with the mean annual precipitations. ► Concentration profile differences were attributed to soil properties, especially the clay content and the pH value. ► A convection–dispersion model with irreversible retention was used to fit the measured 137 Cs concentration profiles.

  1. Effects of moisture and temperature during grain storage on the functional properties and isoflavone profile of soy protein concentrate.

    Science.gov (United States)

    Ziegler, Valmor; Ferreira, Cristiano Dietrich; Hoffmann, Jéssica Fernanda; de Oliveira, Maurício; Elias, Moacir Cardoso

    2018-03-01

    The objective of this study was evaluate the effects of moisture and temperature during grain storage on the functional properties and isoflavone profile of soy protein concentrate. The protein concentrate was extracted from soybeans on the first day of storage and after 12months of storage, at 12 and 15% moisture and at temperatures of 11, 18, 25, and 32°C. The protein concentrate obtained from grains stored at 32°C showed decreased extraction yield (51.6% with 15% of moisture) and protein solubility (24.8% with 15% of moisture) with increased emulsifying capacity (52.2% with 12% of moisture) and foam formation, compared with sample obtained at the start of the storage period. The isoflavone profile showed a decrease in the concentrations of glycosylated, malonyl, and acetyl isoflavones and a corresponding increase in the concentrations of aglycone isoflavones, with the magnitude of these changes increasing with increasing storage temperature and moisture content. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Effect of abnormal outflow from end stages on concentration profile in uranium-stripping bank of PUREX flowsheet

    International Nuclear Information System (INIS)

    Ueda, Yoshinori; Matsumoto, Shiro

    2002-01-01

    The effect of the abnormal outflow from the end stages on the concentration profile was studied for the uranium-stripping bank to consider the design and the operation of the solvent extraction process, which eases the undesirable effects due to such abnormal flow. The abnormal outflow affected the concentration profile in the same manner as the decrease in the rate of the corresponding liquid flow rate entering the bank. The results suggested that the solvent extractor at the aqueous inlet stage in stripping banks and the solvent extractor at the organic inlet stage in extraction banks should be carefully designed to restrict the respective abnormal aqueous and organic outflows within the normal operational liquid flow rate range. Combining the result and the inherent phase separation behavior of the extractor suggested the possibility of designing the process with the self-controlled function of throughput, which eases the change of the concentration profile due to the undesirable increase in the rate of liquid flow rate entering the bank. Basically the proposed approaches are probably applicable to other general extraction and stripping processes. (author)

  3. Pollutant concentration profile reconstruction using digital soft sensors for biodegradation and exposure assessment in the presence of model uncertainty.

    Science.gov (United States)

    Kazantzis, Nikolaos; Kazantzi, Vasiliki; Christodoulou, Emmanuel G

    2014-01-01

    A new approach to the problem of environmental hazard assessment and monitoring for pollutant biodegradation reaction systems in the presence of uncertainty is proposed using soft sensor-based pollutant concentration dynamic profile reconstruction techniques. In particular, a robust reduced-order soft sensor is proposed that can be digitally implemented in the presence of inherent complexity and the inevitable model uncertainty. The proposed method explicitly incorporates all the available information associated with a process model characterized by varying degrees of uncertainty, as well as available sensor measurements of certain physicochemical quantities. Based on the above information, a reduced-order soft sensor is designed enabling the reliable reconstruction of pollutant concentration profiles in complex biodegradation systems that can not be always achieved due to physical and/or technical limitations associated with current sensor technology. The option of using the aforementioned approach to compute toxic load and persistence indexes on the basis of the reconstructed concentration profiles is also pursued. Finally, the performance of the proposed method is evaluated in two illustrative environmental hazard assessment case studies.

  4. Artificial neural networks to evaluate the boron concentration decreasing profile in Blood-BPA samples of BNCT patients

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Reiriz, Alejandro, E-mail: garciareiriz@gmail.com [Department of Analytical Chemistry, Faculty of Biochemical and Pharmaceutical Sciences, National University of Rosario, Rosario Institute of Chemistry (IQUIR-CONICET), Suipacha 531, Rosario S2002LRK (Argentina); Magallanes, Jorge [Comision Nacional de Energia Atomica, Av. Gral. Paz 1499, San Martin, B1650KNA, Buenos Aires (Argentina); Zupan, Jure [National Institute of Chemistry, Hajdrihova 19, SLO-1000 Ljubljana, Eslovenia (Slovenia); Liberman, Sara [Comision Nacional de Energia Atomica, Av. Gral. Paz 1499, San Martin, B1650KNA, Buenos Aires (Argentina)

    2011-12-15

    For the prediction of decay concentration profiles of the p-boronophenylalanine (BPA) in blood during BNCT treatment, a method is suggested based on Kohonen neural networks. The results of a model trained with the concentration profiles from the literature are described. The prediction of the model was validated by the leave-one-out method. Its robustness shows that it is mostly independent on small variations. The ability to fit retrospective experimental data shows an uncertainty lower than the two compartment model used previously. - Highlights: Black-Right-Pointing-Pointer We predicted decaying concentration profiles of BPA in blood during BNCT therapy. Black-Right-Pointing-Pointer Is suggested a method based on Kohonen neural networks. Black-Right-Pointing-Pointer The results show that it is very robust and mostly independent of small variations. Black-Right-Pointing-Pointer It has a better ability to fit retrospective experimental data. Black-Right-Pointing-Pointer The model could be progressively improved by adding new data to the training matrix.

  5. High-Resolution Vertical Profile Measurements for Carbon Dioxide and Water Vapour Concentrations Within and Above Crop Canopies

    Science.gov (United States)

    Ney, Patrizia; Graf, Alexander

    2018-03-01

    We present a portable elevator-based facility for measuring CO2, water vapour, temperature and wind-speed profiles between the soil surface and the atmospheric surface layer above crop canopies. The end of a tube connected to a closed-path gas analyzer is continuously moved up and down over the profile range (in our case, approximately 2 m) while concentrations are logged at a frequency of 20 s^{-1}. Using campaign measurements in winter wheat, winter barley and a catch crop mixture (spring 2015 to autumn 2016) during different stages of crop development and different times of the day, we demonstrate a simple approach to correct for time lags, and the resulting profiles of 30-min mean mole fractions of CO2 and H2O over height increments of 0.025 m. The profiles clearly show the effects of soil respiration and photosynthetic carbon assimilation, varying both during the diurnal cycle and during the growing season. Profiles of temperature and wind speed are based on a ventilated finewire thermocouple and a hot-wire anemometer, respectively. Measurements over bare soil and a short plant canopy were analyzed in the framework of Monin-Obukhov similarity theory to check the validity of the measurements and raw-data-processing approach. Derived fluxes of CO2, latent and sensible heat and momentum show good agreement with eddy-covariance measurements.

  6. Profile of rheumatology patients willing to report adverse drug reactions: bias from selective reporting

    Directory of Open Access Journals (Sweden)

    Protić D

    2016-02-01

    Full Text Available Dragana Protić,1 Nada Vujasinović-Stupar,2 Zoran Bukumirić,3 Slavica Pavlov-Dolijanović,4 Snežana Baltić,5 Slavica Mutavdžin,6 Ljiljana Markovic-Denić,7 Marija Zdravković,8 Zoran Todorović1 1Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; 2Department 2, Institute of Rheumatology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; 3Institute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; 4Department 5, Institute of Rheumatology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; 5Department 5, Institute of Rheumatology, Belgrade, Serbia; 6Institute of Physiology “Rihard Burjan”, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; 7Institute of Epidemiology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; 8Department of Cardiology, Medical Center “Bežanijska kosa”, Faculty of Medicine, University of Belgrade, Belgrade, Serbia Background: Adverse drug reactions (ADRs have a significant impact on human health and health care costs. The aims of our study were to determine the profile of rheumatology patients willing to report ADRs and to identify bias in such a reporting system. Methods: Semi-intensive ADRs reporting system was used in our study. Patients willing to participate (N=261 completed the questionnaire designed for the purpose of the study at the hospital admission. They were subsequently classified into two groups according to their ability to identify whether they had experienced ADRs during the previous month. Group 1 included 214 out of 261 patients who were able to identify ADRs, and group 2 consisted of 43 out of 261 patients who were not able to identify ADRs in their recent medical history. Results: Group 1 patients were more significantly aware of their diagnosis than the patients from group 2. Marginal significance was found

  7. Driving under the influence of drugs in Sweden with zero concentration limits in blood for controlled substances.

    Science.gov (United States)

    Jones, Alan Wayne

    2005-12-01

    This article describes the background and implementation in Sweden of zero-concentration limits for controlled drugs in the blood of drivers. Eliminating the need to prove that a person's ability to drive safely was impaired by drugs has greatly simplified the prosecution case, which now rests primarily on the forensic toxicology report. Driving under the influence of a prescription drug listed as a controlled substance is exempt from the zero-limit law provided the medication was being used in accordance with a physician's direction and the person was not considered unfit to drive. The prevalence of driving under the influence of drugs (DUID) in Sweden was evaluated from police reports with the main focus on the toxicological findings. A large case series of DUID suspects was compared before and after introducing zero concentration limits in blood for controlled substances on July 1, 1999. The spectrum of drugs used by typical offenders and the concentrations of various licit and illicit substances in blood were evaluated and compared. Immediately after the zero-limit law came into force, the number of cases of DUID submitted by the police for toxicological analysis increased sharply and is currently ten-fold higher than before the new legislation. Statistics show that about 85% of all blood samples sent for toxicological analysis have one or more banned substances present. Amphetamine is by far the leading drug of abuse in Sweden and was identified in about 50-60% of all DUID suspects either alone or together with other controlled substances. The next most frequently encountered illicit drug was tetrahydrocannabinol (THC), with positive findings in about 20-25% of cases. Various prescription drugs, mainly sedative-hypnotics like diazepam and flunitrazepam, were also highly prevalent and these occurred mostly together with illicit substances. Opiates, such as 6-acetyl morphine and morphine, the metabolites of heroin, were high on the list of substances identified

  8. Control of Sewer systems and Wastewater treatment plants using pollutant concentration profiles

    DEFF Research Database (Denmark)

    Bechmann, Henrik; Nielsen, Marinus K.; Madsen, Henrik

    1998-01-01

    On-line measurements of pollutants in the wastewater combined with grey-box modelling are used to estimate the amount of deposits in the sewer system. The pollutant mass flow at the wastewater treatment plant is found to consist of a diurnal profile minus the deposited amount of pollutants...

  9. Global LC/MS Metabolomics Profiling of Calcium Stressed and Immunosuppressant Drug Treated Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Stefan Jenkins

    2013-12-01

    Full Text Available Previous studies have shown that calcium stressed Saccharomyces cerevisiae, challenged with immunosuppressant drugs FK506 and Cyclosporin A, responds with comprehensive gene expression changes and attenuation of the generalized calcium stress response. Here, we describe a global metabolomics workflow for investigating the utility of tracking corresponding phenotypic changes. This was achieved by efficiently analyzing relative abundance differences between intracellular metabolite pools from wild-type and calcium stressed cultures, with and without prior immunosuppressant drugs exposure. We used pathway database content from WikiPathways and YeastCyc to facilitate the projection of our metabolomics profiling results onto biological pathways. A key challenge was to increase the coverage of the detected metabolites. This was achieved by applying both reverse phase (RP and aqueous normal phase (ANP chromatographic separations, as well as electrospray ionization (ESI and atmospheric pressure chemical ionization (APCI sources for detection in both ion polarities. Unsupervised principle component analysis (PCA and ANOVA results revealed differentiation between wild-type controls, calcium stressed and immunosuppressant/calcium challenged cells. Untargeted data mining resulted in 247 differentially expressed, annotated metabolites, across at least one pair of conditions. A separate, targeted data mining strategy identified 187 differential, annotated metabolites. All annotated metabolites were subsequently mapped onto curated pathways from YeastCyc and WikiPathways for interactive pathway analysis and visualization. Dozens of pathways showed differential responses to stress conditions based on one or more matches to the list of annotated metabolites or to metabolites that had been identified further by MS/MS. The purine salvage, pantothenate and sulfur amino acid pathways were flagged as being enriched, which is consistent with previously published

  10. Genome-wide codon usage profiling of ocular infective Chlamydia trachomatis serovars and drug target identification.

    Science.gov (United States)

    Sadhasivam, Anupriya; Vetrivel, Umashankar

    2017-07-04

    Chlamydia trachomatis (C.t) is a Gram-negative obligate intracellular bacteria and is a major causative of infectious blindness and sexually transmitted diseases. Among the varied serovars of this organism, A, B and C are reported as prominent ocular pathogens. Genomic studies of these strains shall aid in deciphering potential drug targets and genomic influence on pathogenesis. Hence, in this study we performed deep statistical profiling of codon usage in these serovars. The overall base composition analysis reveals that these serovars are over biased to AU than GC. Similarly, relative synonymous codon usage also showed preference towards A/U ending codons. Parity Rule 2 analysis inferred unequal distribution of AT and GC, indicative of other unknown factors acting along with mutational pressure to influence codon usage bias (CUB). Moreover, absolute quantification of CUB also revealed lower bias across these serovars. The effect of natural selection on CUB was also confirmed by neutrality plot, reinforcing natural selection under mutational pressure turned to be a pivotal role in shaping the CUB in the strains studied. Correspondence analysis (COA) clarified that, C.t C/TW-3 to show a unique trend in codon usage variation. Host influence analysis on shaping the codon usage pattern also inferred some speculative relativity. In a nutshell, our finding suggests that mutational pressure is the dominating factor in shaping CUB in the strains studied, followed by natural selection. We also propose potential drug targets based on cumulative analysis of strand bias, CUB and human non-homologue screening.

  11. Synthesis, characterization, release kinetics and toxicity profile of drug-loaded starch nanoparticles.

    Science.gov (United States)

    El-Naggar, Mehrez E; El-Rafie, M H; El-sheikh, M A; El-Feky, Gina S; Hebeish, A

    2015-11-01

    The current research work focuses on the medical application of the cost-effective cross-linked starch nanoparticles, for the transdermal delivery using Diclofenac sodium (DS) as a model drug. The prepared DS-cross-linked starch nanoparticles were synthesized using nanoprecipitation technique at different concentrations of sodium tripolyphosphate (STPP) in the presence of Tween 80 as a surfactant. The resultant cross-linked starch nanoparticles loaded with DS were characterized using world-class facilities such as TEM, DLS, FT-IR, XRD, and DSc. The efficiency of DS loading was also evaluated via entrapment efficiency as well as in vitro release and histopathological study on rat skin. The optimum nanoparticles formulation selected by the JMP(®) software was the formula that composed of 5% maize starch, 57.7mg DS and 0.5% STPP and 0.4% Tween 80, with particle diameter of about 21.04nm, polydispersity index of 0.2 and zeta potential of -35.3mV. It is also worth noting that this selected formula shows an average entrapment efficiency of 95.01 and sustained DS release up to 6h. The histophathological studies using the best formula on rat skin advocate the use of designed transdermal DS loaded cross-linked starch nanoparticles as it is safe and non-irritant to rat skin. The overall results indicate that, the starch nanoparticles could be considered as a good carrier for DS drug regarding the enhancement in its controlled release and successful permeation, thus, offering a promising nanoparticulate system for the transdermal delivery non-steroidal anti-inflammatory drug (NSAID). Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Prevalence of alcohol and other drugs and the concentrations in blood of drivers killed in road traffic crashes in Sweden.

    Science.gov (United States)

    Ahlner, Johan; Holmgren, Anita; Jones, Alan Wayne

    2014-03-01

    Drunk or drug-impaired drivers represent a major public health and societal problem worldwide. Because over 95% of drivers killed on the roads in Sweden are autopsied, reliable information is available about the use of alcohol and/or other drug before the crash. This retrospective 4-year study (2008-2011) used a forensic toxicology database (TOXBASE) to evaluate the concentrations of alcohol and other drugs in blood samples from drivers killed in road-traffic crashes. The mean age of all victims (N = 895) was 48 ± 20 years, and the majority were male (86%). In 504 drivers (56%), the results of toxicological analysis were negative and these victims were older; mean age (± SD) 47 ± 20 years, than alcohol positive cases (35 ± 14 years) and illicit drug users (34 ± 15 years). In 21% of fatalities, blood-alcohol concentration (BAC) was above the statutory limit for driving (0.2 g/L), although the median BAC was appreciably higher (1.72 g/L). Illicit drugs (mainly amphetamine and cannabis) were identified in ~7% of victims, either alone (2.5%), together with alcohol (1.8%) or a prescription drug (2%). The psychoactive prescription drugs identified were mainly benzodiazepines, z-hypnotics and tramadol, which were found in the blood of 7.6% of crash victims. The high median BAC in fatally-injured drivers speaks strongly towards alcohol-induced impairment as being responsible for the crash. Compared with alcohol, the prevalence of illicit and psychoactive prescription drugs was fairly low despite a dramatic increase in the number of drug-impaired drivers arrested by the police after a zero-tolerance law was introduced in 1999.

  13. MicroRNA expression profiles associated with development of drug resistance in Ehrlich ascites tumor cells

    DEFF Research Database (Denmark)

    Husted, Susanne; Søkilde, Rolf; Rask, Lene

    2011-01-01

    Multidrug resistance (MDR) poses a major obstacle to successful chemotherapeutic treatment of cancer, and often involves multiple genes, which may be regulated post-transcriptionally by microRNAs (miRNAs). The purpose of the present study was therefore to identify any resistance-associated changes...... in miRNA expression in a sensitive and five increasingly drug-resistant Ehrlich ascites tumor (EAT) cell lines, representing different steps in the development of resistance. We used an LNA-enhanced microarray platform to study the global miRNA expression profiles in the six murine EAT cell lines......, and identified growth-, hypoxia-, and resistance-specific miRNA patterns. Among the differentially expressed miRNAs, we found the two clusters miR-183∼miR-96∼miR-182 and miR-200b∼miR-200a∼miR-429 as well as miR-141 to be consistently upregulated in the MDR cell lines, while miR-125b-5p and the two clusters mi...

  14. Adverse drug reaction profile of anti-snake venom in a rural tertiary care teaching hospital

    Science.gov (United States)

    Deshpande, Rushikesh Prabhakar; Motghare, Vijay Motiram; Padwal, Sudhir Laxman; Pore, Rakesh Ramkrishna; Bhamare, Chetanraj Ghanshyam; Deshmukh, Vinod Shivaji; Pise, Harshal Nutan

    2013-01-01

    Objectives The study was carried out with the aim of evaluation of the adverse drug reaction profile of anti-snake venom serum (ASV) in a rural tertiary care hospital. Methods An observational study was conducted in SRTR Medical College, Ambajogai, Maharashtra, India. A total number of 296 indoor case papers of snake bite from February to September 2011 and June to August 2012 were retrieved from the record section and the antivenom reactions were assessed. In addition, basic epidemiological data and prescribing practices of ASV were also analyzed. Results Vasculotoxic snake bites were more common (50.61%) than neuroparalytic ones (22.56%). Mild envenomation was the commonest presentation. A total of 92 (56.10%) patients who received ASV suffered from antivenom reactions. The most common nature of reaction was chills, rigors (69.56%) followed by nausea and vomiting (34.8%). 10-15% patients suffered from moderate to severe reactions like hypotension and sudden respiratory arrest. We did not find any dose response relationship of ASV to risk of reactions (odds ratio 0.37). Intradermal sensitivity test was performed in about 72% cases. Conclusion Our study showed a higher incidence of reactions to ASV at our institute. PMID:24396245

  15. Standard drug concentrations and smart-pump technology reduce continuous-medication-infusion errors in pediatric patients.

    Science.gov (United States)

    Larsen, Gitte Y; Parker, Howard B; Cash, Jared; O'Connell, Mary; Grant, MaryJo C

    2005-07-01

    To determine if combining standard drug concentrations with "smart-pump" technology reduces reported medication-infusion errors. Preintervention and postintervention comparison of reported medication errors related to infusion therapies during the calendar years 2002 and 2003. A 242-bed university-affiliated tertiary pediatric hospital. Change in continuous-medication-infusion process, comprising the adoption of (1) standard drug concentrations, (2) "smart" syringe pumps, and (3) human-engineered medication labels. Comparison of reported continuous-medication-infusion errors before and after the intervention. The number of reported errors dropped by 73% for an absolute risk reduction of 3.1 to 0.8 per 1000 doses. Preparation errors that occurred in the pharmacy decreased from 0.66 to 0.16 per 1000 doses; the number of 10-fold errors in dosage decreased from 0.41 to 0.08 per 1000 doses. The use of standard drug concentrations, smart syringe pumps, and user-friendly labels reduces reported errors associated with continuous medication infusions. Standard drug concentrations can be chosen to allow most neonates to receive needed medications without concerns related to excess fluid administration.

  16. Effects of age, adipose percent, and reproduction on PCB concentrations and profiles in an extreme fasting North Pacific marine mammal.

    Directory of Open Access Journals (Sweden)

    Sarah H Peterson

    Full Text Available Persistent organic pollutants, including polychlorinated biphenyls (PCBs, are widely distributed and detectable far from anthropogenic sources. Northern elephant seals (Mirounga angustirostris biannually travel thousands of kilometers to forage in coastal and open-ocean regions of the northeast Pacific Ocean and then return to land where they fast while breeding and molting. Our study examined potential effects of age, adipose percent, and the difference between the breeding and molting fasts on PCB concentrations and congener profiles in blubber and serum of northern elephant seal females. Between 2005 and 2007, we sampled blubber and blood from 58 seals before and after a foraging trip, which were then analyzed for PCBs. Age did not significantly affect total PCB concentrations; however, the proportion of PCB congeners with different numbers of chlorine atoms was significantly affected by age, especially in the outer blubber. Younger adult females had a significantly greater proportion of low-chlorinated PCBs (tri-, tetra-, and penta-CBs than older females, with the opposite trend observed for hepta-CBs, indicating that an age-associated process such as parity (birth may significantly affect congener profiles. The percent of adipose tissue had a significant relationship with inner blubber PCB concentrations, with the highest mean concentrations observed at the end of the molting fast. These results highlight the importance of sampling across the entire blubber layer when assessing contaminant levels in phocid seals and taking into account the adipose stores and reproductive status of an animal when conducting contaminant research.

  17. Profiling of drug binding proteins by monolithic affinity chromatography in combination with liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Zhang, Xuepei; Wang, Tongdan; Zhang, Hanzhi; Han, Bing; Wang, Lishun; Kang, Jingwu

    2014-09-12

    A new approach for proteome-wide profiling drug binding proteins by using monolithic capillary affinity chromatography in combination with HPLC-MS/MS is reported. Two immunosuppresive drugs, namely FK506 and cyclosporin A, were utilized as the experimental models for proof-of-concept. The monolithic capillary affinity columns were prepared through a single-step copolymerization of the drug derivatives with glycidyl methacrylate and ethylene dimethacrylate. The capillary chromatography with the affinity monolithic column facilitates the purification of the drug binding proteins from the cell lysate. By combining the capillary affinity column purification and the shot-gun proteomic analysis, totally 33 FK506- and 32 CsA-binding proteins including all the literature reported target proteins of these two drugs were identified. Among them, two proteins, namely voltage-dependent anion-selective channel protein 1 and serine/threonine-protein phosphatase PGAM5 were verified by using the recombinant proteins. The result supports that the monolithic capillary affinity chromatography is likely to become a valuable tool for profiling of binding proteins of small molecular drugs as well as bioactive compounds. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2013-01-01

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

  19. Platinum-based anticancer drugs in waste waters of a major UK hospital and predicted concentrations in recipient surface waters.

    Science.gov (United States)

    Vyas, Nitin; Turner, Andrew; Sewell, Graham

    2014-09-15

    Concentrations of the cytotoxic platinum-based anticancer drugs, as total Pt, have been measured over a three week period in one of the main drains and in the effluent of the oncology ward of a major UK hospital (Derriford, Plymouth). Concentrations of Pt were highly variable in both discharges, and ranged from about 0.02 to 140 μg L(-1) in the oncology effluent and from about 0.03 to 100 μg L(-1) in the main drain. A comparison of drug administration figures over the study period with an estimate of the quantity of Pt discharged through the drains suggests that about 22% of total Pt is emitted to the environment from the hospital with the remainder being discharged by treated patients in the wider community. Administration figures for the three Pt-based drugs used in the hospital (cisplatin, carboplatin and oxaliplatin) coupled with published measurements on the removal of the drugs by conventional sewage treatment allowed the concentrations of Pt arising from each drug to be predicted in recipient surface waters as a function of water flow rate. For conditions representative of the region under study, concentrations of total Pt between a few tens and in excess of 100 pg L(-1) are predicted, with the principal form of the metal occurring as carboplatin and its metabolites. Although predicted concentrations are below EMEA guidelines warranting further risk assessment, the presence of substances in surface waters that are potentially carcinogenic, mutagenic and teratogenic and yet whose environmental effects are not understood is cause for concern. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Effect of balanced concentrate ration on the performance and hematobiochemical profile of lactating native ewes and lambs in coastal Odisha

    Directory of Open Access Journals (Sweden)

    Sasanka Sekhar Beura

    2014-12-01

    Full Text Available Aim: The present study was conducted to evaluate the effect of supplementation of balanced concentrate ration during lactation on the growth performance, blood and metabolic profiles of native ewes and lambs in coastal Odisha. Materials and Methods: A total of 40 numbers of lactating ewes of the same parity comprised the experimental animals. The selected ewes were randomly assigned to two groups of twenty each, maintaining uniformity in body weight (13.36±0.33 kg for Group 1 and 13.48±0.37 kg for Group 2. Group 1 was maintained on grazing only while Group 2 was supplemented with a balanced concentrate mixture @ 200 g/head/day during the first 2 months of lactation. The concentrate was fed individually in separate containers in the morning hours before the animals were taken out for grazing. Results: The ewes in Group 2 registered higher body weights at every fortnight. The differences were found to be highly significant (p<0.01 from 2nd to 5th fortnight and significant (p<0.05 for the remaining fortnights. The ewes in Group 2 showed significantly (p<0.01 higher daily gains than those in Group 1 at every fortnight. The hemoglobin (Hb concentration, mean cell hemoglobin (MCH and total leukocyte count (TLC values were significant (p<0.05 between groups at the end of 4th fortnight after lambing and the mean cell hemoglobin concentration (MCHC values is significantly (p<0.05 higher in Group 2 over Group 1. Conclusion: It was concluded that supplementation of a balanced concentrate mixture (crude protein 18.21% @ 200 g/ewe/day along with grazing during the first 2 months of lactation resulted in higher ewe body weight gain. It improved their hematological and metabolic profiles and also resulted in higher body weight gain in lambs born to these supplemented ewes.

  1. The Impact of Serum Drug Concentration on the Efficacy of Imipramine, Pregabalin and their Combination in Painful Polyneuropathy

    DEFF Research Database (Denmark)

    Sindrup, Søren H; Holbech, Jakob V; Bach, Flemming W.

    2017-01-01

    OBJECTIVE: The serum concentration-effect relation was explored for first line drugs in neuropathic pain and aimed to determine if efficacy could be increased. METHODS: Data from a randomized, placebo-controlled, cross-over trial on imipramine, pregabalin and their combination in painful polyneur......OBJECTIVE: The serum concentration-effect relation was explored for first line drugs in neuropathic pain and aimed to determine if efficacy could be increased. METHODS: Data from a randomized, placebo-controlled, cross-over trial on imipramine, pregabalin and their combination in painful.......4 (95% CI -0.9: 0.1) by pregabalin and -1.6 (95% CI-2.1:-1.1) by combination therapy. On monotherapy, there was no difference between responders and non-responders with respect to concentrations of imipramine (mean 161 nmol/L vs. 229 nmol/L, P=0.129) and pregabalin (mean 9.8 μmol/L vs. 11.7 μmol/L, P=0...... for mono-therapy nor for combination therapy (P=0.161-0.797). Isobulographic presentations of reponders with imipramine and pregabalin concentrations during combination therapy did not indicate synergistic interaction. DISCUSSION: There were no important relations between drug concentrations and efficacy...

  2. Concentrations and composition profiles of parabens in currency bills and paper products including sanitary wipes.

    Science.gov (United States)

    Liao, Chunyang; Kannan, Kurunthachalam

    2014-03-15

    Parabens (alkyl esters of p-hydroxybenzoic acid) are widely used as antimicrobial preservatives in personal care products, pharmaceuticals, and foodstuffs. Although parabens have been reported to be used as antimicrobials in certain types of papers (e.g., wet sanitary or hygiene wipes), little is known about the occurrence of these compounds in paper products. In this study, we determined the concentrations of six paraben analogs, methyl (MeP), ethyl (EtP), propyl (PrP), butyl (BuP), benzyl (BzP), and heptyl parabens (HepP), in 253 paper products divided into 18 categories, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). At least one of the six parabens was detected in almost all (detection rate: 98%) paper samples, and the total concentrations (∑PBs; sum of six parabens) ranged from 1.85 to 3,220,000 ng/g (geometric mean (GM): 103; median: 55.1 ng/g). Sanitary wipes contained very high concentrations of ∑PBs (GM: 8300 ng/g). Paper currencies, tickets, business cards, food cartons, flyers, and newspapers contained notable concentrations of ∑PBs, and the GM concentrations in these paper categories were on the order of a few tens to thousands of nanograms per gram. One source of parabens in paper products is the use of these chemicals as antifungal agents. MeP and PrP were the predominant analogs, accounting for approximately 62% and 16% of the total concentrations of parabens, respectively. On the basis of measured concentrations and frequency of handling of paper products, we estimated the daily intake (EDI) of parabens through dermal absorption. The GM and 95th percentile EDI values were 6.31 and 2050 ng/day, respectively, for the general population. Among the paper categories analyzed, sanitary wipes contributed to the majority (>90%) of the exposures. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Linseed oil supplemented concentrate fed to Brahman crossbred fattening steers on carcass quality traits and intramuscular fatty acid profiles

    Directory of Open Access Journals (Sweden)

    Pitunart Noosen

    2017-02-01

    Full Text Available The objective of this study was to determine the linseed oil supplemented concentrate fed to Brahman crossbred fattening steers on carcass quality trait and intramuscular fatty acid (FA profiles. All steers were fed 14% CP concentrate. The treatments included: (1 7 kg/d concentrate; (2 4 kg/d concentrate supplemented with 200 g/d palm oil (PO; (3 4 kg/d concentrate supplemented with 100 g/d PO and 100 g/d linseed oil (LSO; and (4 4 kg/d concentrate supplemented with 200 g/d LSO. The animals in the treatment 1 were fed ad libitum rice straw (RS, whereas the animals in other treatments were fed ad libitum fresh grass (FG. Dietary treatments had no effect on nutrient intake while oil supplement decreased dry matter intake (DMI. Inclusion of LSO did not negatively affect carcass quality, but increasing amount of LSO supplement increased the n-3 fatty acids and lowered the n-6/n-3 ratio in beef

  4. Profiles

    International Nuclear Information System (INIS)

    2004-01-01

    Profiles is a synthetic overview of more than 100 national energy markets in the world, providing insightful facts and key energy statistics. A Profile is structured around 6 main items and completed by key statistics: Ministries, public agencies, energy policy are concerned; main companies in the oil, gas, electricity and coal sectors, status, shareholders; reserve, production, imports and exports, electricity and refining capacities; deregulation of prices, subsidies, taxes; consumption trends by sector, energy market shares; main energy projects, production and consumption prospects. Statistical Profiles are present in about 3 pages the main data and indicators on oil, gas, coal and electricity. (A.L.B.)

  5. Profile of organic acid concentrations in the digestive gland and hemolymph of Biomphalaria glabrata under estivation

    Directory of Open Access Journals (Sweden)

    José Clecildo Barreto Bezerra

    1999-11-01

    Full Text Available Using high performance liquid chromatography (HPLC analysis it was possible to determine simultaneously the concentration of organic acids (pyruvate, lactate, succinate, fumarate, malate, acetate, propionate, acetoacetate, and ß-hydroxybutyrate in the digestive gland and the extracellular concentration of these same acids in the hemolymph of estivating Biomphalaria glabrata, the intermediate host of Schistosoma mansoni. After a 7 day period of estivation, there was a significant increase in the tissue levels of lactate, succinate, malate and acetate compared to non-estivating snails. After 14 days of estivation, the levels of lactate and acetate were also significantly elevated. The hemolymph concentrations of pyruvate and acetate increased significantly after 7 days and acetate concentrations continued to be significantly increased up to 14 days of estivation. The other organic acids studied, such as ketone body acetoacetate and ß-hydroxybutyrate or the volatile acid propionate, did not accumulate. Their tissue concentrations, however, increased on the 7th day of estivation and reached normal levels within two weeks of estivation for some of them. One should take into consideration how the reduction in metabolism can be handled under aerobic conditions, and what role anaerobic pathways may play in both energy formation and redox balance processes.

  6. Tracking control of concentration profiles in a fed-batch bioreactor using a linear algebra methodology.

    Science.gov (United States)

    Rómoli, Santiago; Serrano, Mario Emanuel; Ortiz, Oscar Alberto; Vega, Jorge Rubén; Eduardo Scaglia, Gustavo Juan

    2015-07-01

    Based on a linear algebra approach, this paper aims at developing a novel control law able to track reference profiles that were previously-determined in the literature. A main advantage of the proposed strategy is that the control actions are obtained by solving a system of linear equations. The optimal controller parameters are selected through Monte Carlo Randomized Algorithm in order to minimize a proposed cost index. The controller performance is evaluated through several tests, and compared with other controller reported in the literature. Finally, a Monte Carlo Randomized Algorithm is conducted to assess the performance of the proposed controller. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

  7. Multilayer Coating of Tetrandrine-loaded PLGA nanoparticles: Effect of surface charges on cellular uptake rate and drug release profile.

    Science.gov (United States)

    Meng, Rui; Li, Ke; Chen, Zhe; Shi, Chen

    2016-02-01

    The effect of surface charges on the cellular uptake rate and drug release profile of tetrandrine-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TPNs) was studied. Stabilizer-free nanoprecipitation method was used in this study for the synthesis of TPNs. A typical layer-by-layer approach was applied for multi-coating particles' surface with use of poly(styrene sulfonate) sodium salt (PSS) as anionic layer and poly(allylamine hydrochloride) (PAH) as cationic layer. The modified TPNs were characterized by different physicochemical techniques such as Zeta sizer, scanning electron microscopy and transmission electron microscopy. The drug loading efficiency, release profile and cellular uptake rate were evaluated by high performance liquid chromatography and confocal laser scanning microscopy, respectively. The resultant PSS/PAH/PSS/PAH/TPNs (4 layers) exhibited spherical-shaped morphology with the average size of 160.3±5.165 nm and zeta potential of-57.8 mV. The encapsulation efficiency and drug loading efficiency were 57.88% and 1.73%, respectively. Multi-layer coating of polymeric materials with different charges on particles' surface could dramatically influence the drug release profile of TPNs (4 layers vs. 3 layers). In addition, variable layers of surface coating could also greatly affect the cellular uptake rate of TPNs in A549 cells within 8 h. Overall, by coating particles' surface with those different charged polymers, precise control of drug release as well as cellular uptake rate can be achieved simultaneously. Thus, this approach provides a new strategy for controllable drug delivery.

  8. Polychlorinated biphenyl (PCB) contamination in Galveston Bay, Texas: Comparing concentrations and profiles in sediments, passive samplers, and fish.

    Science.gov (United States)

    Oziolor, Elias M; Apell, Jennifer N; Winfield, Zach C; Back, Jeffrey A; Usenko, Sascha; Matson, Cole W

    2018-05-01

    The industrialized portion of the Houston Ship Channel (HSC) is heavily contaminated with anthropogenic contaminants, most prominent of which are the polychlorinated biphenyls (PCBs). This contamination has driven adaptive evolution in a keystone species for Galveston Bay, the Gulf killifish (Fundulus grandis). We investigated the geographical extent of PCB impacts by sampling 12 sites, ranging from the heavily industrialized upper portion of the HSC to Galveston Island. At each site, PCB concentrations and profiles were determined in three environmental compartments: sediment, water (polyethylene passive samplers), and fish tissue (resident Gulf killifish). We observed a steep gradient of PCB contamination, ranging from 4.00 to 100,000 ng/g organic carbon in sediment, 290-110,000 ng/g lipid in fish, and 4.5-2300 ng/g polyethylene in passive samplers. The PCB congener profiles in Gulf killifish at the most heavily contaminated sites were shifted toward the higher chlorinated PCBs and were highly similar to the sediment contamination profiles. In addition, while magnitude of total PCB concentrations in sediment and total fish contamination levels were highly correlated between sites, the relative PCB congener profiles in fish and passive samplers were more alike. This strong correlation, along with a lack of dependency of biota-sediment accumulation factors with total contamination rates, confirm the likely non-migratory nature of Gulf killifish and suggest their contamination levels are a good site-specific indicator of contamination in the Galveston Bay area. The spatial gradient of PCB contamination in Galveston Bay was evident in all three matrices studied and was observed effectively using Gulf killifish contamination as an environmentally relevant bioindicator of localized contamination in this environment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Elastic recoil detection analysis for the determination of hydrogen concentration profiles in switchable mirrors

    NARCIS (Netherlands)

    Huisman, M.C.; van der Molen, S.J.; Vis, R.D.

    1999-01-01

    Switchable mirrors made of thin films of Y, La or rare-earth (RE) metals exhibit spectacular changes in their optical and electrical properties upon hydrogen loading. The study of these materials has indicated that the occurring phenomena are highly sensitive to the actual hydrogen concentration in

  10. Progesterone Profiles During the Estrous Cycle and Pregnancy of Grazing Bali Cows Supplemented with Concentrate

    Directory of Open Access Journals (Sweden)

    HLL Belli

    2009-05-01

    Full Text Available The influence of concentrate during estrous cycle and pregnancy on pattern of progesterone were studied. Seventeen calf-rearing cows were devided randomly into two groups, group A (N=9 were grazed on natural pasture as basal diet, whereas goup B (n=8 received additional 2.4 kg concentrate consists of 1.2 kg corn meal, 0.6 kg rice bran and 0.6 coconut cake. Animals from each group were closely observed for estrous characteristics i.e. estrus detection two times a day by two experienced technisians. Blood sample taken 3-times per week from jugular vein were used for assessing plasma progesterone concentrations using RIA procedure. Plasma progesterone concentrations were not influenced by concentrate supplementation neither during successive estrous cycles nor during pregnancy. The concentrations began to rise on day 4 of the cycle (1.9 ng/mL and 1.8 ng/mL and increased to concentrations as high as 5.4 ng/mL and 5.1 ng/mL for supplemented and non-supplemented cows during the luteal phase (day 12 before returning to basal levels i.e. 0.1 ng/mL and 0.1 ng/mL, before ovulation. Following conception, plasma progesterone increased from 0,16 ng/mL and 0.21 ng/mL at estrus to 3.6 ng/mL and 2.73 ng/mL at week-1 and then rose to 5.09 and 4.57 ng/mL at week-2 for NS and S groups, respectively. Aftewards, progesterone continued to rise to 5,46 ng/mL and 5.17 ng/mL on week-3, and then reached 6.25 and 5.3 ng/mL for non-supplemented and supplemented cow, respectively. During 10 weeks pre-calving period, progesterone levels declined gradualli achieving levels 2.83 ng/mL and 2.87 ng/mL in the non-supplemented and supplemented groups, respectively, declined markedly 1 to 2 days prior to parturition and remained at these levels before reaching the basal level after parturition. (Animal Production 11(2: 79-87 (2009 Key Words: Bali cows, progesterone, estrous cycle, pregnancy

  11. Cytotoxic and genotoxic effects of high concentrations of the immunosuppressive drugs cyclosporine and tacrolimus in MRC-5 cells.

    Science.gov (United States)

    Cilião, H L; Ribeiro, D L; Camargo-Godoy, R B O; Specian, A F L; Serpeloni, J M; Cólus, I M S

    2015-02-01

    Immunosuppressive drugs are used to suppress immune system activity in transplant patients and reduce the risk of organ rejection. The present study evaluated the potential cytotoxic, genotoxic and mutagenic of the immunosuppressive drugs cyclosporine (CsA) and tacrolimus (FK-506) on normal human fibroblasts (MRC-5 cells). Based on plasma concentrations of the immunosuppressive drugs, which were obtained from the records of kidney transplant patients at the Kidney Institute of Londrina, Brazil, 11 concentrations of each immunosuppressive were chosen to evaluate cell viability using the MTT assay. From these results, CsA and FK-506 concentrations of 135, 300, 675, and 1520 ng/ml and 8, 16, 24, and 32 ng/ml, respectively, were evaluated using (i) the comet assay, (ii) the nuclear division index (NDI), (iii) the micronucleus test (CBMN) and (iv) cell proliferation curves generated by quantifying cell numbers and protein levels. In this study, 1520 to 3420 ng/ml CsA decreased cell viability after 48 h of exposure. Genotoxic effects were observed only with a concentration of 1520 ng/ml after 3h of exposure and with concentrations of 675 and 1520 ng/ml after 24h of exposure. Mutagenic effects were observed only for the concentration of 1520 ng/ml. FK-506 decreased cell viability after 72 h of exposure for concentrations up to 20 ng/ml; genotoxic effects were observed with concentrations up to 8 ng/ml for both treatment times (3 and 24h) and mutagenic effects were observed with concentrations of 24 and 32 ng/ml after 24h of treatment. The cell proliferation curves demonstrated the absence of cytostatic effects of these drugs, and these data were confirmed by the NDI analysis. Our results suggest that concentrations lower than 300 ng/ml of CsA and 16 ng/ml of FK-506 are safe for use, as they did not induce genotoxic and mutagenic damage or affect MRC-5 cell viability and proliferation. Copyright © 2014 Elsevier GmbH. All rights reserved.

  12. Polycyclic aromatic hydrocarbons in urban street dust and surface soil: comparisons of concentration, profile, and source.

    Science.gov (United States)

    Wang, De-Gao; Yang, Meng; Jia, Hong-Liang; Zhou, Lei; Li, Yi-Fan

    2009-02-01

    Street dust and surface soil samples in urban areas of Dalian, a coastal city in Liaoning Province, China, were collected and analyzed for 25 polycyclic aromatic hydrocarbons (PAHs). The concentrations, distribution, and sources of PAHs in dust and soil were determined. The concentrations of total PAHs in street dust ranged between 1890 and 17,070 ng/g (dry weight), with an average of 7460 ng/g, whereas the concentrations of total PAHs in surface soil varied greatly, from 650 to 28,900 ng/g, with a mean value of 6440 ng/g. Statistical paired t-test confirmed that total PAH concentrations have no significant difference between street dust and surface soil. Mean PAH concentrations in two type samples were much higher at industrial sites than at business/residential or garden sites. PAHs were dominated by higher molecular weight PAH (4- to 6-ring) homologues, which accounted for about 73% and 72% of total PAHs in street dust and surface soil, respectively. Principal component analysis was used in source apportionment of PAHs in dust and soil. Pyrogenic and petrogenic sources contributed 70% and 22.4% of total PAHs in street dusts, and fossil fuel (coal and petroleum) and biomass combustion accounted for 64.4% and 5.6% of total PAHs in pyrogenic sources, respectively. In surface soil, total PAHs were dominated by pyrogenic sources. The diagnostic ratios of benz[a]anthracene/chrysene confirmed that PAHs in street dust and surface soil of a Dalian urban zone might come mostly from the emission of local sources.

  13. Lead fluxes, isotopic and concentration profiles in a peat deposit near a lead smelter (Príbram, Czech Republic).

    Science.gov (United States)

    Mihaljevic, M; Zuna, M; Ettler, V; Sebek, O; Strnad, L; Goliás, V

    2006-12-15

    The content and the isotopic composition of lead (Pb) were studied in a peat deposit on the ridge of the Brdy Hills, in the vicinity of the Príbram metallurgical works, in the Czech Republic. Quadrupole ICP MS was employed to determine the elemental composition and (206)Pb/(207)Pb and (208)Pb/(206)Pb isotope ratios. The individual layers were dated using alpha spectrometric measurement of the (210)Pb activity. The historical time period covered by the studied cores reached back to the 18th century. The Pb concentration in the studied profiles varied from 10 to 550 mg kg(-1). The (206)Pb/(207)Pb ratio varied in the range from 1.154 to 1.194 in the individual parts of the profile. The metallurgy of the Pb ores ((206)Pb/(207)Pb approximately 1.16), lithogenic Pb ((206)Pb/(207)Pb approximately 1.2), metallurgical processing of automobile batteries ((206)Pb/(207)Pb approximately 1.17) and the combustion of coal ((206)Pb/(207)Pb approximately 1.17-1.19) yield isotopic signatures that determine the isotope compositions of the individual profiles. Deposition rates between 15 mg m(-2) year(-1) at the beginning of the 19th century and 320 mg m(-2) year(-1) in the 1980s were determined in the dated profiles. The increased deposition rates determined on the dated profiles correspond to the increasing production of Pb ores in the Príbram mining area at the turn of the 19th and 20th centuries. The maximum for metallurgical production corresponds to the highest deposition rates recorded in 1960s and 1970s. The current deposition rate of 5-89 mg m(-2) year(-1) Pb is related to erosion of contaminated soils and waste dumps.

  14. Pathogens Causing Blood Stream Infections and their Drug Susceptibility Profile in Immunocompromised Patients

    International Nuclear Information System (INIS)

    Fayyaz, M.; Mirza, I.A.; Ikram, A.; Hussain, A.; Ghafoor, T.; Shujat, U.

    2013-01-01

    Objective: To determine the types of pathogens causing blood stream infections and their drug susceptibility profile in immunocompromised patients. Study Design: Cross-sectional, observational study. Place and Duration of Study: Department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi, from January to September 2012. Methodology: Blood culture bottles received from immunocompromised patients were dealt by two methods, brain heart infusion (BHI) broth based manual method and automated BACTEC system. The samples yielding positive growth from either of two methods were further analyzed. The identification of isolates was done with the help of biochemical reactions and rapid tests. Antimicrobial susceptibility of the isolates was carried out as per recommendations of Clinical and Laboratory Standards Institute (CLSI). Results: Out of the 938 blood culture specimens received from immunocompromised patients, 188 (20%) yielded positive growth. Out of these, 89 (47.3%) isolates were Gram positive and Gram negative each, while 10 (5.3%) isolates were fungi (Candida spp.). In case of Gram positive isolates, 75 (84.3%) were Staphylococcus spp. and 51 (67%) were Methicillin resistant. Amongst Gram negative group 49 (55.1%) isolates were of enterobacteriaceae family, while 40 (44.9%) were non-lactose fermenters (NLF). In vitro antimicrobial susceptibility of Staphylococci revealed 100% susceptibility to vancomycin and linezolid. The enterobacteriaceae isolates had better susceptibility against amikacin 85.7% compared to tigecycline 61.2% and imipenem 59.2%. For NLF, the in vitro efficacy of aminoglycosides was 72.5%. Conclusion: The frequency of Gram positive and Gram negative organisms causing blood stream infections in immunocompromised patients was equal. Vancomycin in case of Gram positive and amikacin for Gram negative organisms revealed better in vitro efficacy as compared to other antibiotics. (author)

  15. Proteomic profiling in incubation medium of mouse, rat and human precision-cut liver slices for biomarker detection regarding acute drug-induced liver injury

    NARCIS (Netherlands)

    van Swelm, Rachel P. L.; Hadi, Mackenzie; Laarakkers, Coby M. M.; Masereeuw, Rosalinde; Groothuis, Geny M. M.; Russel, Frans G. M.

    Drug-induced liver injury is one of the leading causes of drug withdrawal from the market. In this study, we investigated the applicability of protein profiling of the incubation medium of human, mouse and rat precision-cut liver slices (PCLS) exposed to liver injury-inducing drugs for biomarker

  16. Effects of drugs in subtoxic concentrations on the metabolic fluxes in human hepatoma cell line Hep G2

    International Nuclear Information System (INIS)

    Niklas, Jens; Noor, Fozia; Heinzle, Elmar

    2009-01-01

    Commonly used cytotoxicity assays assess the toxicity of a compound by measuring certain parameters which directly or indirectly correlate to the viability of the cells. However, the effects of a given compound at concentrations considerably below EC 50 values are usually not evaluated. These subtoxic effects are difficult to identify but may eventually cause severe and costly long term problems such as idiosyncratic hepatotoxicity. We determined the toxicity of three hepatotoxic compounds, namely amiodarone, diclofenac and tacrine on the human hepatoma cell line Hep G2 using an online kinetic respiration assay and analysed the effects of subtoxic concentrations of these drugs on the cellular metabolism by using metabolic flux analysis. Several changes in the metabolism could be detected upon exposure to subtoxic concentrations of the test compounds. Upon exposure to diclofenac and tacrine an increase in the TCA-cycle activity was observed which could be a signature of an uncoupling of the oxidative phosphorylation. The results indicate that metabolic flux analysis could serve as an invaluable novel tool for the investigation of the effects of drugs. The described methodology enables tracking the toxicity of compounds dynamically using the respiration assay in a range of concentrations and the metabolic flux analysis permits interesting insights into the changes in the central metabolism of the cell upon exposure to drugs.

  17. Concentrations and profiles of PCDD/Fs in sediments of major Polish rivers and the Gdansk Basin--Baltic Sea.

    Science.gov (United States)

    Niemirycz, Elżbieta; Jankowska, Daria

    2011-10-01

    The present state of contamination of bottom sediments in southern part of the Baltic Sea with PCDD/Fs was compared to the findings made for the north-western and eastern Baltic Sea coastal areas of Finland, Sweden and Denmark. The extent of the study area--from marine the Gdańsk Basin, the lower Oder and Vistula Rivers up till Włocławek reservoir--allowed to obtain the sediment samples with diversified properties. Dioxin's concentrations in sediments examined in the Polish costal area allows us to evaluate this zone as relatively less contaminated. Higher dioxin concentration has been found in Wloclawek Dam Reservoir. Differences in congener patterns and temporal changes in marine sediment profiles were examined. The highest concentrations of tetra- and penta-congeners still remain in the surface layer of Gdansk Deep, whereas the decline in concentrations of these most toxic congeners, have been observed in the sediments from some other parts of the Baltic coast. Excess concentration of dioxins in sediments has a great impact on human being due to special ability of accumulation in the trophic chain as well as in water (fishes) and land (milk, meat). Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. A comparative performance study of a photovoltaic concentrator system with discrete mirror and continuos profile for two different absorber shapes

    Energy Technology Data Exchange (ETDEWEB)

    H, Saiful; Rezau, K.M [University of Dhaka, Dhaka (Bangladesh)

    2000-07-01

    Profiles of parabolic concentrators of discrete mirror and continuos surface mirror have been designed for combined electrical thermal photovoltaic systems. In the design the changes of concentration ratio, effect of reflection, angle of incidence over the absorber have been taken into account for maximum energy collection. The performances of the system are studied for solar cells of modified grid finger for illuminations from 1-10 sun. The local concentration ratio (LCR) distribution over the absorbers for both the concentrator, the optical efficiency, thermal efficiency, electrical and thermal power output and overall efficiency have been evaluated for different values of beam radiation concentration ratio and focal distance. [Spanish] Se han disenado perfiles de concentradores parabolicos de espejo discreto y de superficie continua para sistemas fotovoltaicos combinados electricos y termicos. En el diseno los cambios de la proporcion de concentracion, del efecto de la reflexion, del angulo de incidencia sobre el observador se han tenido en cuenta para una maxima recoleccion de energia. Los rendimientos del sistema se han estudiado para celdas solares de parrilla modificada para iluminaciones solares de 1-10. Han sido evaluados para diferentes valores de la proporcion de la concentracion de la radiacion en el rayo y la distancia focal la proporcion de concentracion local (LCR) de la distribucion en los absorbedores, para el concentrador la eficiencia optica, la eficiencia termica, electrica, la produccion de energia termica y electrica y la eficiencia total.

  19. Plutonium and americium concentrations and vertical profiles in some Italian mosses used as bioindicators

    International Nuclear Information System (INIS)

    Testa, C.; Desideri, D.; Meli, M.A.; Guerra, F.; Degetto, S.; Jia, G.; Gerdol, R.

    1998-01-01

    We have examined the uptake of actinide elements Am and Pu by different species of lichen and moss collected in two locations (Urbino, Central Italy; Alps region, North-east Italy). Plutonium and americium were separated and determined by extraction chromatography, electrodeposition and alpha-spectrometry. This paper summarizes our results with a special emphasis on the vertical profiles of these actinides in two different species of mosses. Several 1-2 cm depth sections were obtained and dated by 210 Pb method. A typical peak for 239,240 Pu and 241 Am was found in the very old moss species ('Sphagnum Compactum') at a depth corresponding to the period 1960-1970 which was the period characterized by the maximum nuclear weapon tests. In a younger moss species ('Neckeria Crispa') no peak was observed and the regression curves showed that Am is more mobile than 239,240 Pu and 238 Pu. (author)

  20. Fine mapping the spatial distribution and concentration of unlabeled drugs within tissue micro-compartments using imaging mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Anna Nilsson

    Full Text Available Readouts that define the physiological distributions of drugs in tissues are an unmet challenge and at best imprecise, but are needed in order to understand both the pharmacokinetic and pharmacodynamic properties associated with efficacy. Here we demonstrate that it is feasible to follow the in vivo transport of unlabeled drugs within specific organ and tissue compartments on a platform that applies MALDI imaging mass spectrometry to tissue sections characterized with high definition histology. We have tracked and quantified the distribution of an inhaled reference compound, tiotropium, within the lungs of dosed rats, using systematic point by point MS and MS/MS sampling at 200 microm intervals. By comparing drug ion distribution patterns in adjacent tissue sections, we observed that within 15 min following exposure, tiotropium parent MS ions (mass-to-charge; m/z 392.1 and fragmented daughter MS/MS ions (m/z 170.1 and 152.1 were dispersed in a concentration gradient (80 fmol-5 pmol away from the central airways into the lung parenchyma and pleura. These drug levels agreed well with amounts detected in lung compartments by chemical extraction. Moreover, the simultaneous global definition of molecular ion signatures localized within 2-D tissue space provides accurate assignment of ion identities within histological landmarks, providing context to dynamic biological processes occurring at sites of drug presence. Our results highlight an important emerging technology allowing specific high resolution identification of unlabeled drugs at sites of in vivo uptake and retention.

  1. Effect of Na2SO3 concentration to drug loading and drug release of ascorbic acid in chitosan edible film as drug delivery system membrane

    Directory of Open Access Journals (Sweden)

    Kistriyani Lilis

    2018-01-01

    Full Text Available Chitosan is a type of carbohydrate compounds produced from waste marine products, in particular the class of shrimp, crabs and clams. Chitosan is often process into edible films and utilized for food packaging also has potential as a membrane for drug delivery system. Drug loading and drug release can be controlled by improve the characteristics of the membrane by adding crosslinker. The purpose of this research is to study the effect of addition of crosslinker to the rate of loading and release of ascorbic acid in the chitosan edible film. Na2SO3 was used as crosslinker. Two grams of chitosan was dissolved into 100 ml of distilled water. Acetic acid and plasticizer were added in the solution then heated at 50°C. Na2SO3 solution with mass various of Na2SO3 dissolved, 01026 0.3; and 0.5 grams were added about 30 mL to make edible film. The analysis include of drug loading, drug release and tensile strength. The result showed that the loading of edible film with crosslinker 0.15 g; 0.3 g; and 0.5 g respectively were 60.98 ppm; 52.53 ppm; and 40.88 ppm, meanwhile for the release with crosslinker 0.15 g; 0.3 g; and 0.5 g respectively were 3.78 ppm; 5.72 ppm; and 5.97 ppm.

  2. Violent Behaviors in Drug Addiction: Differential Profiles of Drug-Addicted Patients with and without Violence Problems

    Science.gov (United States)

    Fernandez-Montalvo, Javier; Lopez-Goni, Jose J.; Arteaga, Alfonso

    2012-01-01

    This study explored the prevalence of violent behaviors in patients who are addicted to drugs. A sample of 252 addicted patients (203 male and 49 female) who sought outpatient treatment was assessed. Information on violent behaviors, sociodemographic factors, consumption factors (assessed by the European version of the Addiction Severity Index…

  3. The internet as a source of drug information: a profile of utilization by ...

    African Journals Online (AJOL)

    Introduction: The internet is a useful tool which could provide quality drug information if well applied. Its utilization as a source of drug information by junior doctors in Nigeria is not well documented. Objective: To assess the use of the internet by junior doctors as a source of objective drug information in Nigeria. Methods: The ...

  4. The importance of Pharmacovigilance for the drug safety: Focus on cardiovascular profile of incretin-based therapy.

    Science.gov (United States)

    Sportiello, Liberata; Rafaniello, Concetta; Scavone, Cristina; Vitale, Cristiana; Rossi, Francesco; Capuano, Annalisa

    2016-01-01

    With the recent introduction of the new European Pharmacovigilance legislation, all new drugs must be carefully monitored after admission on the European market, in order to assess the long safety profile. Currently, special attention is given to several hypoglycemic agents with recent market approval (agonists of glucagon-like peptide-1 [GLP-1] receptor and dipeptidyl peptidase 4 inhibitors [DPP-4i]), which act through the potentiation of incretin hormone signaling. Their inclusion in European additional monitoring is also due to safety problems, which seem to characterize their pharmacological class. In fact, these drugs initially showed a good tolerability profile with mainly gastrointestinal adverse events, low risk of hypoglycemia and minor effects on body weight. But, new concerns such as infections, pancreatitis, pancreatic cancer and above all cardiovascular events (especially risk of heart failure requiring hospitalization) are now arising. In this review, we highlighted aspects of the new Pharmacovigilance European dispositions, and then we investigated the tolerability profile of incretin-based therapies, in particular DPP-4 inhibitors. Notably, we focused our attention on new safety concerns, which are emerging mostly in the post-marketing period, as the cardiovascular risk profile. Evidence in literature and opinions of regulatory agencies (e.g., European Medicines Agency and Food and Drug Administration) about risks of incretin-based therapies are yet controversial, and there are many open questions in particular on cancer and cardiovascular effects. Thus, it is important to continue to monitor closely the use of these drugs in clinical practice to improve the knowledge on their long-term safety and their place in diabetes therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Soil erosion determination using the Cs-137 concentration in the soil profile, in a rain fall seasonal ecosystem of Mexico

    International Nuclear Information System (INIS)

    Martinez, L.R.; Garcia, O.F.; Mass, J.M.

    1992-01-01

    The soils erosion is one of the main processes of environmental degradation. Latin America presents high levels of erosion however the works that quantificate this problem are few. The application of methods agreed to the tropical countries conditions represents an important limitation in the developing of these works. A methodological option that has arisen in the last years is the application of the distribution analysis of Cs-137 concentration in the soil profile, for estimating the soil motion in a seasonal tropical ecosystem in Chamela, Jalisco, Mexico. The low concentrations of Cs-137 were determined with a gamma spectroscopy system of high resolution and low noise. It is confirmed that the redistribution of Cs-137 in the landscape depends on erosive processes. The conclusion is that in the interpretation of Cs-137 levels it is necessary to incorporate morphology analysis of declivity since this is a low scale measurement. (Author)

  6. An Excel®-based visualization tool of 2-D soil gas concentration profiles in petroleum vapor intrusion.

    Science.gov (United States)

    Verginelli, Iason; Yao, Yijun; Suuberg, Eric M

    2016-01-01

    In this study we present a petroleum vapor intrusion tool implemented in Microsoft ® Excel ® using Visual Basic for Applications (VBA) and integrated within a graphical interface. The latter helps users easily visualize two-dimensional soil gas concentration profiles and indoor concentrations as a function of site-specific conditions such as source strength and depth, biodegradation reaction rate constant, soil characteristics and building features. This tool is based on a two-dimensional explicit analytical model that combines steady-state diffusion-dominated vapor transport in a homogeneous soil with a piecewise first-order aerobic biodegradation model, in which rate is limited by oxygen availability. As recommended in the recently released United States Environmental Protection Agency's final Petroleum Vapor Intrusion guidance, a sensitivity analysis and a simplified Monte Carlo uncertainty analysis are also included in the spreadsheet.

  7. Therapeutic drug monitoring of cerebrospinal fluid vancomycin concentration during intraventricular administration.

    Science.gov (United States)

    Popa, D; Loewenstein, L; Lam, S W; Neuner, E A; Ahrens, C L; Bhimraj, A

    2016-02-01

    Limited data are available on intraventricular vancomycin dosing for meningitis. This study explored clinical characteristics that correlated with cerebrospinal fluid (CSF) concentrations. Over a nine-year period, 13 patients with 34 CSF vancomycin concentrations were evaluated. CSF output and time from dose correlated with CSF vancomycin concentration. No relationship was seen with regards to CSF protein, white blood cell count or glucose. Copyright © 2015. Published by Elsevier Ltd.

  8. Metabolic and muscle damage profiles of concentric versus repeated eccentric cycling.

    Science.gov (United States)

    Peñailillo, Luis; Blazevich, Anthony; Numazawa, Hideo; Nosaka, Kazunori

    2013-09-01

    Eccentric cycling is an exercise modality that could elicit multiple health benefits with low metabolic cost, but unaccustomed performance results in significant muscle damage. It is not known whether muscle damage is attenuated when eccentric cycling is repeated; thus, this study compared metabolic and muscle damage responses to concentric (CONC) and two consecutive eccentric (ECC1 and ECC2) cycling bouts. Ten men (28 ± 8 yr) performed each cycling bout for 30 min at 60% of the maximal concentric power output at 60 rpm, with 2 wk between bouts. HR, oxygen consumption (V˙O2), blood lactate (BLa), RPE, and muscle activity (EMG) data were collected during cycling. Maximal voluntary isometric knee extensor (MVC) strength, squat (SJ), countermovement jump (CMJ) height, muscle soreness indicators, and plasma creatine kinase (CK) activity were measured before, immediately after, and 1-4 d after exercise. Average HR, V˙O2, BLa, and RPE were lower (P < 0.05) during ECC1 than CONC, and EMG amplitude was also lower during ECC1 than CONC. Decreases in MVC, CMJ, and SJ and the increase in muscle soreness were greater (P x0003C; 0.05) after ECC1 than CONC. Increases in creatine kinase were minimal after all bouts. When comparing ECC1 and ECC2, HR and BLa were lower (P < 0.05) during ECC2 than ECC1, and decreases in MVC, CMJ, and SJ and the increase in muscle soreness were greater (P < 0.05) after ECC1 than ECC2. After ECC2, MVC, CMJ, and SJ did not change and no muscle soreness was developed. Eccentric cycling was less metabolically demanding than concentric cycling, and HR and BLa were further reduced during ECC2. Muscle damage is minimal after ECC2 and should not influence the choice to undertake eccentric cycling training.

  9. Cell Line Derived 5-FU and Irinotecan Drug-Sensitivity Profiles Evaluated in Adjuvant Colon Cancer Trial Data

    DEFF Research Database (Denmark)

    Buhl, Ida Kappel; Gerster, Sarah; Delorenzi, Mauro

    2016-01-01

    PURPOSE: This study evaluates whether gene signatures for chemosensitivity for irinotecan and 5-fluorouracil (5-FU) derived from in vitro grown cancer cell lines can predict clinical sensitivity to these drugs. METHODS: To test if an irinotecan signature and a SN-38 signature could identify...... patients who benefitted from the addition of irinotecan to 5-FU, we used gene expression profiles based on cell lines and clinical tumor material. These profiles were applied to expression data obtained from pretreatment formalin fixed paraffin embedded (FFPE) tumor tissue from 636 stage III colon cancer...... patients enrolled in the PETACC-3 prospective randomized clinical trial. A 5-FU profile developed similarly was assessed by comparing the PETACC-3 cohort with a cohort of 359 stage II colon cancer patients who underwent surgery but received no adjuvant therapy. RESULTS: There was no statistically...

  10. Profiles in drug metabolism and toxicology: Richard Tecwyn Williams (1909-1979).

    Science.gov (United States)

    Jones, Alan Wayne

    2015-01-01

    This article pays homage to the life and work of a veritable pioneer in toxicology and drug metabolism, namely a Welshman, Richard Tecwyn Williams, FRS. Professor Williams, or RT as he was known, made major contributions to knowledge about the metabolism and toxicology of drugs and xenobiotics during a scientific career spanning nearly 50 years. Author or coauthor of close to 400 research articles and reviews, including a classic book, entitled Detoxication Mechanisms, Williams and his research school investigated virtually all aspects of drug metabolism, especially conjugations. In particular, the concepts of phase 1 and phase II metabolic pathways were introduced by Williams; the biliary excretion of drugs was extensively studied as were species differences in drug metabolism and detoxication. Besides investigating the metabolism of many pharmaceutical drugs, such as sulfonamides and thalidomide, Williams and his group investigated the disposition and fate in the body of organic pesticides and recreational drugs of abuse, such as amphetamine, methamphetamine and lysergic acid diethylamide (LSD).

  11. An alkaline comet assay study on the antimalarial drug atovaquone in human peripheral blood lymphocytes: a study based on clinically relevant concentrations.

    Science.gov (United States)

    Dinter, Domagoj; Gajski, Goran; Garaj-Vrhovac, Vera

    2013-01-01

    Atovaquone, a hydroxynaphthoquinone, is an anti-parasite drug, selectively targeting the mitochondrial respiratory chain of malaria parasite. It is used for both the treatment and prevention of malaria, usually in a fixed combination with proguanil. Although atovaquone has not often been associated with severe adverse reactions in the recommended dosages and has a relatively favorable side effect profile, the present study was undertaken to evaluate its cytogenotoxic potential towards human peripheral blood lymphocytes. Two different concentrations of atovaquone found in plasma when used in fixed-dose combination with proguanile hydrochloride were used with and without S9 metabolic activation: 2950 ng ml(-1) used for prophylactic treatment and 11 800 ng ml(-1) used in treatment of malaria. The results showed that lymphocyte viability was not affected after the treatment, suggesting that atovaquone was not cytotoxic in the given concentrations. With the alkaline comet assay we demonstrated that in human peripheral blood lymphocytes no significant changes in comet parameters occurred after the treatment. There were no differences in tested parameters with the addition of S9 metabolic activation, indicating that atovaquone either has no metabolite or it is not toxic in the given concentrations. Since no effects were observed after the treatment, it is to be concluded that atovaquone is safe from the aspect of genototoxicity in the recommended dosages. Copyright © 2011 John Wiley & Sons, Ltd.

  12. Dynamic Analysis of the Temperature and the Concentration Profiles of an Industrial Rotary Kiln Used in Clinker Production

    Directory of Open Access Journals (Sweden)

    DIULIA C.Q. RODRIGUES

    Full Text Available ABSTRACT Cement is one of the most used building materials in the world. The process of cement production involves numerous and complex reactions that occur under different temperatures. Thus, there is great interest in the optimization of cement manufacturing. Clinker production is one of the main steps of cement production and it occurs inside the kiln. In this paper, the dry process of clinker production is analysed in a rotary kiln that operates in counter flow. The main phenomena involved in clinker production is as follows: free residual water evaporation of raw material, decomposition of magnesium carbonate, decarbonation, formation of C3A and C4AF, formation of dicalcium silicate, and formation of tricalcium silicate. The main objective of this study was to propose a mathematical model that realistically describes the temperature profile and the concentration of clinker components in a real rotary kiln. In addition, the influence of different speeds of inlet gas and solids in the system was analysed. The mathematical model is composed of partial differential equations. The model was implemented in Mathcad (available at CCA/UFES and solved using industrial input data. The proposal model is satisfactory to describe the temperature and concentration profiles of a real rotary kiln.

  13. Dynamic Analysis of the Temperature and the Concentration Profiles of an Industrial Rotary Kiln Used in Clinker Production.

    Science.gov (United States)

    Rodrigues, Diulia C Q; Soares, Atílio P; Costa, Esly F; Costa, Andréa O S

    2017-01-01

    Cement is one of the most used building materials in the world. The process of cement production involves numerous and complex reactions that occur under different temperatures. Thus, there is great interest in the optimization of cement manufacturing. Clinker production is one of the main steps of cement production and it occurs inside the kiln. In this paper, the dry process of clinker production is analysed in a rotary kiln that operates in counter flow. The main phenomena involved in clinker production is as follows: free residual water evaporation of raw material, decomposition of magnesium carbonate, decarbonation, formation of C3A and C4AF, formation of dicalcium silicate, and formation of tricalcium silicate. The main objective of this study was to propose a mathematical model that realistically describes the temperature profile and the concentration of clinker components in a real rotary kiln. In addition, the influence of different speeds of inlet gas and solids in the system was analysed. The mathematical model is composed of partial differential equations. The model was implemented in Mathcad (available at CCA/UFES) and solved using industrial input data. The proposal model is satisfactory to describe the temperature and concentration profiles of a real rotary kiln.

  14. Development of a μDissolution-Permeation model with in situ drug concentration monitoring

    DEFF Research Database (Denmark)

    Berthelsen, Ragna; Byrialsen, Julie Pelle; Holm, René

    2016-01-01

    state biorelevant medium consisting of HBSS pH 6.5 supplemented with bile salts and lecithin was used as the apical dissolution media, while HBSS pH 7.4 was used as the basolateral medium. The apparent permeability (Papp) and dissolution-time profiles for albendazole, felodipine and fenofibrate were...

  15. Measurement of Fuel Concentration Profile at Leading Edge of Lifted Flame with Acetone Laser-Induced Fluorescence

    Science.gov (United States)

    Hirota, Mitsutomo; Sekine, Kazushi; Hashimoto, Kouta; Saiki, Atsushi; Takahashi, Hidemi; Masuya, Goro

    This is a study of the leading-edge characteristics of a methane-air triple flame. Few experiment results are available for physical examination of such characteristics, so further experimental investigations are strongly needed to understand the stability mechanism in a mixture with a steep concentration gradient. To this end, we measured concentration profiles at the leading edge of a flame using acetone laser-induced fluorescence (acetone LIF). The results demonstrated that the lifted height of the flame changed when acetone was added to the mixture and correlated well with increased C2 radical behind the flame edge. However, the OH radical luminous intensity, measured with a spectroscope, did not change with addition of acetone. Moreover, the burning velocity obtained by the Bunsen-burner method remained constant when acetone was added to the mixture. Therefore, acetone had little influence on burning intensity. Acetone LIF can thus be employed to measure the local concentration gradient at the leading edge of a flame. The acetone LIF signals could be corrected to consider the thermal effect by using silicone oil vanishing-plane data. From the corrected acetone LIF data, the width between the lean and rich flammability limits (flammability limit width) in the flow upstream of the flame with a steep concentration gradient was clearly observed and could be quantitatively compared with the recent numerical results.

  16. What’s normal? Oligosaccharide concentrations and profiles in milk produced by healthy women vary geographically12

    Science.gov (United States)

    Meehan, Courtney L; McGuire, Mark A; Foster, James; Sellen, Daniel W; Kamau-Mbuthia, Elizabeth W; Kamundia, Egidioh W; Mbugua, Samwel; Moore, Sophie E; Prentice, Andrew M; Kvist, Linda J; Otoo, Gloria E; Brooker, Sarah L; Price, William J; Shafii, Bahman; Placek, Caitlyn; Lackey, Kimberly A; Robertson, Bianca; Ruíz, Lorena; Pareja, Rossina G; Bode, Lars

    2017-01-01

    Background: Human milk is a complex fluid comprised of myriad substances, with one of the most abundant substances being a group of complex carbohydrates referred to as human milk oligosaccharides (HMOs). There has been some evidence that HMO profiles differ in populations, but few studies have rigorously explored this variability. Objectives: We tested the hypothesis that HMO profiles differ in diverse populations of healthy women. Next, we examined relations between HMO and maternal anthropometric and reproductive indexes and indirectly examined whether differences were likely related to genetic or environmental variations. Design: In this cross-sectional, observational study, milk was collected from a total of 410 healthy, breastfeeding women in 11 international cohorts and analyzed for HMOs by using high-performance liquid chromatography. Results: There was an effect of the cohort (P 4 times higher in milk collected in Sweden than in milk collected in rural Gambia (mean ± SEM: 473 ± 55 compared with 103 ± 16 nmol/mL, respectively; P < 0.05), and disialyllacto-N-tetraose (DSLNT) concentrations ranged from 216 ± 14 nmol/mL (in Sweden) to 870 ± 68 nmol/mL (in rural Gambia) (P < 0.05). Maternal age, time postpartum, weight, and body mass index were all correlated with several HMOs, and multiple differences in HMOs [e.g., lacto-N-neotetrose and DSLNT] were shown between ethnically similar (and likely genetically similar) populations who were living in different locations, which suggests that the environment may play a role in regulating the synthesis of HMOs. Conclusions: The results of this study support our hypothesis that normal HMO concentrations and profiles vary geographically, even in healthy women. Targeted genomic analyses are required to determine whether these differences are due at least in part to genetic variation. A careful examination of sociocultural, behavioral, and environmental factors is needed to determine their roles in this regard. This

  17. Evaluations of dielectric property and drug release profile of 5-FU patches based on plasma charged electrets

    Science.gov (United States)

    Wang, YUAN; Hejuan, LIANG; Ping, HUANG; Xiaoqiang, AN; Jian, JIANG; Lili, CUI

    2018-05-01

    In the present study, the electret 5-fluorouracil patch was developed, the effective surface potential, piezoelectric coefficient d 33, open-circuit thermally stimulated discharge (TSD) current spectra and shear adhesion of the patch were measured. The drug release profile of the patch was determined by using high performance liquid chromatography method. A stable potential difference which was positively dependent on the surface potential of the electret was generated on two sides of the patch. The measurements of d 33 coefficient, TSD current spectra and adhesion performance showed that the electrostatic field of the electret could cause polarization and cohesive strength decreasing of the matrix molecules, change the distribution and interaction of the drug molecules in patch, therefore to increase the release of drug from the transdermal patch.

  18. Gene expression profile of coronary artery cells treated with nonsteroidal anti-inflammatory drugs reveals off-target effects.

    Science.gov (United States)

    Palayoor, Sanjeewani T; J-Aryankalayil, Molykutty; Makinde, Adeola Y; Cerna, David; Falduto, Michael T; Magnuson, Scott R; Coleman, C Norman

    2012-06-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have come under scrutiny because of the gastrointestinal, renal, and cardiovascular toxicity associated with prolonged use of these drugs. The purpose of this study was to identify molecular targets for NSAIDs related to cellular toxicity with a view to optimize drug efficacy in the clinic. Coronary artery smooth muscle cells and endothelial cells were treated with low (clinically achievable) and high (typically used in preclinical studies) concentrations of celecoxib, NS398, and ibuprofen for 24 hours. NSAIDs-induced gene expression changes were evaluated by microarray analysis and validated by real-time reverse-transcription polymerase chain reaction and western blotting. The functional significance of differentially expressed genes was evaluated by Ingenuity Pathway Analysis. At high concentrations, NSAIDs altered the expression of genes regulating cell proliferation and cell death. NSAIDs also altered genes associated with cardiovascular functions including inflammation, thrombosis, fibrinolysis, coronary artery disease, and hypertension. The gene expression was most impacted by ibuprofen, celecoxib, and NS398, in that order. This study revealed that NSAIDs altered expression of an array of genes associated with cardiovascular events and emphasizes the potential for fingerprinting drugs in preclinical studies to assess the potential drug toxicity and to optimize the drug efficacy in clinical settings.

  19. Genetic diversity & drug sensitivity profiles of Mycobacterium tuberculosis isolates from two slums of Jaipur city, Rajasthan, India.

    Science.gov (United States)

    Malhotra, Bharti; Dashora, Deepti; Kumar, Vipin; Goyal, Sumit; Sharma, Bhavana; Kumar, Madhu; Gupta, Kailash Narayan; Sharma, Vishnu Dutt; Chauhan, D S; Katoch, Kiran; Katoch, Vishwa Mohan

    2017-01-01

    Slums are considered as hotspots of tuberculosis (TB). The study of genetic diversity and drug susceptibility profile of Mycobacterium tuberculosis (MTB) will help understand the transmission dynamics and can be used for better prevention and control of the disease. The aim of this study was to determine the drug susceptibility profiles and genetic diversity using the random amplified polymorphic DNA (RAPD) and mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU VNTR) of MTB isolates from sputum samples of pulmonary TB patients residing in the two slums of Jaipur city in Rajasthan, India. Sputum samples collected from pulmonary TB patients, their contacts and suspects during 2010-2012 were processed for microscopy and mycobacterial culture. Drug susceptibility testing was done by one per cent indirect proportion method on Lowenstein-Jensen medium for first-line anti-TB drugs rifampicin, isoniazid, ethambutol and streptomycin. MTB DNA was extracted by physicochemical method, and DNA fingerprinting was done by RAPD and MIRU VNTR analysis. Among 175 sputum samples collected, 75 were positive (43.8%) for acid-fast bacilli, 83 for MTB culture and four were contaminated. Fifty two isolates (62.7%) were fully sensitive to four drugs, and five (6%) were multidrug resistant (MDR). RAPD analysis of 81 isolates revealed six clusters containing 23 (28.4%) isolates, and 58 (71.6%) were unique. MIRU VNTR analysis clustered 20 (24.7%) isolates, and 61 (75.3%) were unique. About 62.7 per cent isolates from the sputum samples from slum areas were sensitive to four drugs; six per cent of isolates were MDR. Poly-resistance other than MDR was high (16%). About one-fourth isolates were clustered by either method. RAPD was rapid, less expensive but had low reproducibility. MIRU VNTR analysis could identify to greater extent the epidemiological link in the population studied.

  20. Mass Spectrometry to Determine Intracellular Concentrations of Antiretroviral Drugs: From chemistry to clinical application

    NARCIS (Netherlands)

    J.J.A. van Kampen (Jeroen)

    2009-01-01

    textabstractAround 1995 – 1996, treatment options for patients infected with the human immunodefiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS) 1, 2, improved dramatically. Therapy with a combination of several classes of antiretroviral drugs resulted in a

  1. Validation of an ultra-high-performance liquid chromatography-tandem mass spectrometry method to quantify illicit drug and pharmaceutical residues in wastewater using accuracy profile approach.

    Science.gov (United States)

    Hubert, Cécile; Roosen, Martin; Levi, Yves; Karolak, Sara

    2017-06-02

    The analysis of biomarkers in wastewater has become a common approach to assess community behavior. This method is an interesting way to estimate illicit drug consumption in a given population: by using a back calculation method, it is therefore possible to quantify the amount of a specific drug used in a community and to assess the consumption variation at different times and locations. Such a method needs reliable analytical data since the determination of a concentration in the ngL -1 range in a complex matrix is difficult and not easily reproducible. The best analytical method is liquid chromatography - mass spectrometry coupling after solid-phase extraction or on-line pre-concentration. Quality criteria are not specially defined for this kind of determination. In this context, it was decided to develop an UHPLC-MS/MS method to analyze 10 illicit drugs and pharmaceuticals in wastewater treatment plant influent or effluent using a pre-concentration on-line system. A validation process was then carried out using the accuracy profile concept as an innovative tool to estimate the probability of getting prospective results within specified acceptance limits. Influent and effluent samples were spiked with known amounts of the 10 compounds and analyzed three times a day for three days in order to estimate intra-day and inter-day variations. The matrix effect was estimated for each compound. The developed method can provide at least 80% of results within ±25% limits except for compounds that are degraded in influent. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Alterations in Polysomnographic (PSG profile in drug-naïve Parkinson′s disease

    Directory of Open Access Journals (Sweden)

    Sanju P Joy

    2014-01-01

    Full Text Available Objective: We studied the changes in Polysomnographic (PSG profile in drug-naïve patients of Parkinson′s disease (PD who underwent evaluation with sleep overnight PSG. Materials and Methods: This prospective study included 30 with newly diagnosed levodopa-naïve patients with PD, fulfilling the UK-PD society brain bank clinical diagnostic criteria (M:F = 25:5; age: 57.2 ± 10.7 years. The disease severity scales and sleep related questionnaires were administered, and then patients were subjected to overnight PSG. Results: The mean duration of illness was 9.7 ± 9.5 months. The mean Hoehn and Yahr stage was 1.8 ± 0.4. The mean Unified Parkinson′s Disease Rating Scale (UPDRS motor score improved from 27.7 ± 9.2 to 17.5 ± 8.9 with sustained usage of levodopa. Nocturnal sleep as assessed by Pittsburgh Sleep Quality Index (PSQI was impaired in 10 (33.3% patients (mean PSQI score: 5.1 ± 3.1. Excessive day time somnolence was recorded in three patients with Epworth Sleepiness Scale (ESS score ≥ 10 (mean ESS score: 4.0 ± 3.4. PSG analysis revealed that poor sleep efficiency of <85% was present in 86.7% of patients (mean: 68.3 ± 21.3%. The latencies to sleep onset (mean: 49.8 ± 67.0 minutes and stage 2 sleep (36.5 ± 13.1% were prolonged while slow wave sleep was shortened. Respiration during sleep was significantly impaired in which 43.3% had impaired apnoea hyperpnoea index (AHI ≥5, mean AHI: 8.3 ± 12.1. Apnoeic episodes were predominantly obstructive (obstructive sleep apnea, OSA index = 2.2 ± 5.1. These patients had periodic leg movement (PLM disorder (56.7% had PLM index of 5 or more, mean PLMI: 27.53 ± 4 9.05 that resulted in excessive daytime somnolence. Conclusions: To conclude, sleep macro-architecture is altered in frequently and variably in levodopa-naοve patients of PD and the alterations are possibly due to disease process per se.

  3. Measuring plasma paracetamol concentrations in all patients with drug overdose or altered consciousness: Does it change outcome?

    Science.gov (United States)

    Dargan, P; Ladhani, S; Jones, A

    2001-01-01

    Objective—To assess whether measuring plasma paracetamol concentrations in all patients with drug overdose or collapse (altered consciousness) changes outcome. Method—A retrospective survey was performed of all patients attending the Accident and Emergency Department at Guy's Hospital, London over a 12 month period who had plasma paracetamol concentrations measured (it is hospital policy that patients presenting after any drug overdose, or with a collapse/altered consciousness have a plasma paracetamol concentration). Results—A total of 440 patients were identified who had plasma paracetamol concentrations measured, of whom 411 were eligible for the study. Altogether 115 patients presented after a collapse and paracetamol was detected in four of these. A total of 296 patients presented after a drug overdose—136 denied overdose with a paracetamol containing product and paracetamol was not detected in any of these 136 cases. Of the remaining 160 patients who gave a positive history for overdose with paracetamol, 122 presented within 24 hours and 94 had detectable paracetamol values with 16 cases above the treatment line, 12 presented more than 24 hours after ingestion, and 26 presented with a staggered overdose. One patient died as a result of paracetamol overdose. Conclusions—This is the first study in the United Kingdom to evaluate the clinical value of routine paracetamol levels in patients presenting to the emergency department after any overdose or a collapse. Taking blood samples for plasma paracetamol estimation in patients who deny taking paracetamol is of little clinical value. However, there is the potential for missing significant paracetamol poisoning in patients presenting with collapse and so screening with a plasma paracetamol concentration is clinically justified in these patients. Such an approach can only be justified in a country in which paracetamol poisoning is prevalent, such as the United Kingdom. PMID:11354207

  4. 3-D thermalhydraulics flow effects on wall concentration gradient profiles of corrosion/precipitation phenomena in LBE loop fittings

    International Nuclear Information System (INIS)

    Armbya, Narain; Li, Guanjun; Chen, Yitung; Moujaes, Samir

    2004-01-01

    Work is ongoing at UNLV to provide a computer simulation framework that will characterize the behavior and effect of thermalhydraulics on the corrosion/precipitation chemical kinetics processes that take place on the inside surfaces of an LBE flow loop. To that end detailed models are being constructed to study these effects first in several expected loop fittings such as sudden expansion and tee-fittings. The typical flow rates chosen for these simulations are typical of design criteria chosen for the loop with Re numbers expected around 200,000 and the usual axial temperature profiles which are being characterized in the DELTA loop at LANL. STAR-CD is the simulation package used to make these predictions which include detailed 3-D velocity, temperature and concentration gradient profiles of the corrosion/precipitation on the inner surface of these fittings initially. The different predicted variables from these simulations indicate that special attention needs to be placed when designing loops with these fittings especially in the regions of sudden velocity changes and stagnation zones. These wall gradients can determine eventually the expected longevity of these fittings in an LBE flow environment. Presently though very little experimental data exists that would be suitable to corroborate the simulation results. Graphs of concentration gradient v/s distance from the inlet of these fittings were plotted. Eventually these individual fitting models will become part of an overall closed loop that will yield more realistic core concentration values and hence more realistic wall gradient values which are dependent on these core values. (author)

  5. A Profile of Substance Abuse, Gender, Crime, and Drug Policy in the United States and Canada

    Science.gov (United States)

    Grant, Judith

    2009-01-01

    The climate of domestic drug policy in the United States as it pertains to both women and men at the beginning of the 21st century is the criminalization mode of regulation--a mode that is based on the model of addiction as a crime and one that is used to prohibit the use of illegal drugs. In Canada, drug policy is based mainly on the harm…

  6. The Potential of The Synergy of Sunphotometer and Lidar Data to Validate Vertical Profiles of The Aerosol Mass Concentration Estimated by An Air Quality Model

    Directory of Open Access Journals (Sweden)

    Siomos N.

    2016-01-01

    Full Text Available Vertical profiles of the aerosol mass concentration derived by the Lidar/Radiometer Inversion Code (LIRIC, that uses combined sunphotometer and lidar data, were used in order to validate the aerosol mass concentration profiles estimated by the air quality model CAMx. Lidar and CIMEL measurements performed at the Laboratory of Atmospheric Physics of the Aristotle University of Thessaloniki, Greece (40.5N, 22.9E from the period 2013-2014 were used in this study.

  7. Superior Effects of Eccentric to Concentric Knee Extensor Resistance Training on Physical Fitness, Insulin Sensitivity and Lipid Profiles of Elderly Men

    OpenAIRE

    Chen, Trevor Chung-Ching; Tseng, Wei-Chin; Huang, Guan-Ling; Chen, Hsin-Lian; Tseng, Kuo-Wei; Nosaka, Kazunori

    2017-01-01

    It has been reported that eccentric training of knee extensors is effective for improving blood insulin sensitivity and lipid profiles to a greater extent than concentric training in young women. However, it is not known whether this is also the case for elderly individuals. Thus, the present study tested the hypothesis that eccentric training of the knee extensors would improve physical function and health parameters (e.g., blood lipid profiles) of older adults better than concentric trainin...

  8. Drug-drug interaction profile of components of a fixed combination of netupitant and palonosetron: Review of clinical data.

    Science.gov (United States)

    Natale, James J; Spinelli, Tulla; Calcagnile, Selma; Lanzarotti, Corinna; Rossi, Giorgia; Cox, David; Kashef, Kimia

    2016-06-01

    Neurokinin-1 (NK1) receptor antagonists (RAs) are commonly coadministered with serotonin (5-HT3) RAs (e.g. palonosetron (PALO)) to prevent chemotherapy-induced nausea/vomiting. Netupitant/palonosetron (NEPA), an oral fixed combination of netupitant (NETU)-a new NK1 RA-and PALO, is currently under development. In vitro data suggest that NETU inhibits CYP3A4 and is a substrate for and weak inhibitor of P-glycoprotein (P-gp). This review evaluates potential drug-drug interactions between NETU or NEPA and CYP3A4 substrates/inducers/inhibitors or P-gp substrates in healthy subjects. Pharmacokinetic (PK) parameters were evaluated for each drug when NETU was coadministered with PALO (single doses) and when single doses of NETU or NEPA were coadministered with CYP3A4 substrates (erythromycin (ERY), midazolam (MID), dexamethasone (DEX), or oral contraceptives), inhibitors (ketoconazole (KETO)), or inducers (rifampicin (RIF)), or a P-gp substrate (digoxin (DIG)). Results showed no relevant PK interactions between NETU and PALO. Coadministration of NETU increased MID and ERY exposure and significantly increased DEX exposure in a dose-dependent manner; NETU exposure was unaffected. NEPA coadministration had no clinically significant effect on oral contraception, although levonorgestrel exposure increased. NETU exposure increased after coadministration of NEPA with KETO and decreased after coadministration with RIF; PALO exposure was unaffected. NETU coadministration did not influence DIG exposure. In conclusion, there were no clinically relevant interactions between NETU and PALO, or NEPA and oral contraceptives (based on levonorgestrel and ethinylestradiol exposure). Coadministration of NETU or NEPA with CYP3A4 inducers/inhibitors/substrates should be done with caution. Dose reduction is recommended for DEX. Dose adjustments are not needed for NETU coadministration with P-gp substrates. © The Author(s) 2015.

  9. Neurophysiological and subjective profile of marijuana with varying concentrations of cannabinoids.

    Science.gov (United States)

    Ilan, A B; Gevins, A; Coleman, M; ElSohly, M A; de Wit, H

    2005-09-01

    This study investigated the contribution of different cannabinoids to the subjective, behavioral and neurophysiological effects of smoked marijuana. Healthy marijuana users (12 men, 11 women) participated in four sessions. They were randomly assigned to a low or a high delta9-tetrahydrocannabinol group (THC; 1.8% versus 3.6%). In the four sessions under blinded conditions subjects smoked marijuana cigarettes containing placebo (no active cannabinoids), or cigarettes containing THC with low or high levels of cannabichromene (CBC; 0.1% versus 0.5%) and low or high levels of cannabidiol (CBD; 0.2% versus 1.0%). Dependent measures included subjective reports, measures of cognitive task performance and neurophysiological measures [electroencephalographic (EEG) and event-related potential (ERP)]. Compared to placebo, active THC cigarettes produced expected effects on mood, behavior and brain activity. A decrease in performance, reduction in EEG power and attenuation of ERP components reflecting attentional processes were observed during tests of working memory and episodic memory. Most of these effects were not dose-dependent. Varying the concentrations of CBC and CBD did not change subjects' responses on any of the outcome measures. These findings are consistent with previous studies indicating that THC and its metabolites are the primary active constituents of marijuana. They also suggest that neurophysiological EEG and ERP measures are useful biomarkers of the effects of THC.

  10. Direct measurement of local dissolved oxygen concentration spatial profiles in a cell culture environment.

    Science.gov (United States)

    Kagawa, Yuki; Matsuura, Katsuhisa; Shimizu, Tatsuya; Tsuneda, Satoshi

    2015-06-01

    Controlling local dissolved oxygen concentration (DO) in media is critical for cell or tissue cultures. Various biomaterials and culture methods have been developed to modulate DO. Direct measurement of local DO in cultures has not been validated as a method to test DO modulation. In the present study we developed a DO measurement system equipped with a Clark-type oxygen microelectrode manipulated with 1 μm precision in three-dimensional space to explore potential applications for tissue engineering. By determining the microelectrode tip position precisely against the bottom plane of culture dishes with rat or human cardiac cells in static monolayer culture, we successfully obtained spatial distributions of DO in the medium. Theoretical quantitative predictions fit the obtained data well. Based on analyses of the variance between samples, we found the data reflected "local" oxygen consumption in the vicinity of the microelectrode and the detection of temporal changes in oxygen consumption rates of cultured cells was limited by the diffusion rate of oxygen in the medium. This oxygen measuring system monitors local oxygen consumption and production with high spatial resolution, and can potentially be used with recently developed oxygen modulating biomaterials to design microenvironments and non-invasively monitor local DO dynamics during culture. © 2015 Wiley Periodicals, Inc.

  11. Real-time investigation of human topoisomerase I reaction kinetics using an optical sensor: a fast method for drug screening and determination of active enzyme concentrations

    Science.gov (United States)

    Kristoffersen, Emil L.; Jørgensen, Line A.; Franch, Oskar; Etzerodt, Michael; Frøhlich, Rikke; Bjergbæk, Lotte; Stougaard, Magnus; Ho, Yi-Ping; Knudsen, Birgitta R.

    2015-05-01

    Human DNA topoisomerase I (hTopI) is a nuclear enzyme that catalyzes relaxation of super helical tension that arises in the genome during essential DNA metabolic processes. This is accomplished through a common reaction mechanism shared among the type IB topoisomerase enzymes, including eukaryotic and poxvirus topoisomerase I. The mechanism of hTopI is specifically targeted in cancer treatment using camptothecin derivatives. These drugs convert the hTopI activity into a cellular poison, and hence the cytotoxic effects of camptothecin derivatives correlate with the hTopI activity. Therefore, fast and reliable techniques for high throughput measurements of hTopI activity are of high clinical interest. Here we demonstrate potential applications of a fluorophore-quencher based DNA sensor designed for measurement of hTopI cleavage-ligation activities, which are the catalytic steps affected by camptothecin. The kinetic analysis of the hTopI reaction with the DNA sensor exhibits a characteristic burst profile. This is the result of a two-step ping-pong reaction mechanism, where a fast first reaction, the one creating the signal, is followed by a slower second reaction necessary for completion of the catalytic cycle. Hence, the burst profile holds information about two reactions in the enzymatic mechanism. Moreover, it allows the amount of active enzyme in the reaction to be determined. The presented results pave the way for future high throughput drug screening and the potential of measuring active hTopI concentrations in clinical samples for individualized treatment.Human DNA topoisomerase I (hTopI) is a nuclear enzyme that catalyzes relaxation of super helical tension that arises in the genome during essential DNA metabolic processes. This is accomplished through a common reaction mechanism shared among the type IB topoisomerase enzymes, including eukaryotic and poxvirus topoisomerase I. The mechanism of hTopI is specifically targeted in cancer treatment using

  12. ADVERSE EVENT OF DRUG THERAPY (THE FIRST RESULTS OF THE STUDY ACCORDING TO THE PROFILE OUTPATIENT REGISTER

    Directory of Open Access Journals (Sweden)

    Yu. V. Lukina

    2016-01-01

    Full Text Available Adverse events (As of medicines are becoming a more serious problem of health care and society due to the growth of the pharmaceutical market. Incomplete information about AEs of drug therapy is an important aspect of this problem. The use of the register method is very promising in the study of adverse drug reactions in clinical practice. Aim. To study the AEs of drug therapy in the PROFILE outpatient register. Material and methods. Primary patients (n=1531 were included into the PROFILE outpatient register from January 2011 to August 2015. The median age of patients was 63 (54; 71 years. The registration card of patients and patient questionnaires were used within the register for the database creation. Analysis of retrospective data of the register was fulfilled Results. Various AEs were reported in 223 (14.6% patients. Total anamnestic information on 301 cases of AEs was collected: 223 cases were recorded once, 63 – twice, 15 – three times. Patients with AEs were older than patients without AEs ((p<0.0001. AEs were registered most frequently in the use of ACE inhibitors and acetylsalicylic acid: an average of 15% of all cases, each. Various allergic reactions and symptoms of gastrointestinal disorders (pain, nausea, vomiting, diarrhea, etc. were leaders in the structure of AEs. Naturally there were more patients without AEs among those, who did not take medications. Among patients treated with 6 to 10 medications per day, there were 1.5 times more people who had at least one AE (p<0.0001. Conclusion. The use of the register method allows to add information about the safety of various drugs. However, analysis of the prospective data of the PROFILE register looks the most promising for the solution of this problem.

  13. Polycyclic aromatic hydrocarbons in soils and lichen from the western Tibetan Plateau: Concentration profiles, distribution and its influencing factors.

    Science.gov (United States)

    Zhou, Ruichen; Yang, Ruiqiang; Jing, Chuanyong

    2018-05-15

    The Tibetan Plateau (TP) is a huge area and rarely affected by human activity, and is regarded as one of the most remote regions on the earth. Many studies about the long-range atmospheric transport (LRAT) of semi-volatile organic compounds (SVOCs) were conducted in southern and central TP. However, there are very limited studies focused on PAHs in the western TP and the concentrations profiles, distribution and its controlling factors in this area remains unclear. Thus, to explore this knowledge gap, 37 surface soil samples and 23 lichen samples were collected and analyzed for PAHs. The total concentration of 16 US EPA's priority PAHs (∑ 16 PAHs) in western TP ranges 14.4-59.5ng/g and 38.0-133ng/g dry weight (dw) with a mean value of 30.8 and 84.6ng/g dw in soil and lichen, respectively, which is lower than the concentrations in most remote areas worldwide. In the western TP, low molecular weight PAHs (2-3 rings) are dominant (occupied 77.4% and 87.9% on average in soil and lichen, respectively), implying a significant contribution of LRAT in this area. The significant linear correlations (R 2 = 0.372-0.627, p < 0.05) between longitude and soil concentration suggest a strong impact of the westerly wind on the distribution of PAHs in soil. In addition, the concentration ratio of lichen/soil (L/S) was found to linearly increase with the increasing log K OA of individual PAH, suggesting lichen has a strong ability in filtering more lipophilic airborne pollutants in western TP. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Gut Microbiota, Microinflammation, Metabolic Profile, and Zonulin Concentration in Obese and Normal Weight Subjects

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    Agnieszka Żak-Gołąb

    2013-01-01

    Full Text Available The association between gut microbiota and circulating zonulin level, a marker of intestinal permeability, has not been studied yet. The aim of the study is the assessment of plasma zonulin, haptoglobin and proinflammatory cytokines (TNF-α and IL-6 levels in relation to composition of gut microbiota in obese and normal weight subjects. Circulating inflammation markers, such as TNF-α, sTNFR1, sTNFR2, IL-6, zonulin, and haptoglobin levels were measured and semiquantitative analysis of gut microbiota composition was carried out in 50 obese and 30 normal weight subjects without concomitant diseases. Higher circulating zonulin, TNF-α, sTNFR1, sTNFR2, and IL-6 levels were found in the obese subjects. Plasma zonulin level correlated positively with age (r=0.43, P<0.001, body mass (r=0.30, P<0.01, BMI (r=0.33, P<0.01, fat mass and fat percentage (r=0.31, P<0.01 and r=0.23, P<0.05, resp.. Positive correlations between bacterial colony count and sTNFR1 (r=0.33, P<0.01 and plasma zonulin (r=0.26, P<0.05 but not haptoglobin levels were found. Additionally, plasma zonulin level was proportional to daily energy intake (r=0.27, P<0.05 and serum glucose concentration (r=0.18, P<0.05 and inversely proportional to diet protein percentage (r=-0.23, P<0.05. Gut microbiota-related systemic microinflammation in the obese is reflected by circulating zonulin level, a potential marker of interstitial permeability.

  15. Rheological profiling of organogels prepared at critical gelling concentrations of natural waxes in a triacylglycerol solvent.

    Science.gov (United States)

    Patel, Ashok R; Babaahmadi, Mehrnoosh; Lesaffer, Ans; Dewettinck, Koen

    2015-05-20

    The aim of this study was to use a detailed rheological characterization to gain new insights into the gelation behavior of natural waxes. To make a comprehensive case, six natural waxes (differing in the relative proportion of chemical components: hydrocarbons, fatty alcohols, fatty acids, and wax esters) were selected as organogelators to gel high-oleic sunflower oil. Flow and dynamic rheological properties of organogels prepared at critical gelling concentrations (Cg) of waxes were studied and compared using drag (stress ramp and steady flow) and oscillatory shear (stress and frequency sweeps) tests. Although, none of the organogels satisfied the rheological definition of a "strong gel" (G″/G' (ω) ≤ 0.1), on comparing the samples, the strongest gel (highest critical stress and dynamic, apparent, and static yield stresses) was obtained not with wax containing the highest proportion of wax esters alone (sunflower wax, SFW) but with wax containing wax esters along with a higher proportion of fatty alcohols (carnauba wax, CRW) although at a comparatively higher Cg (4%wt for latter compared to 0.5%wt for former). As expected, gel formation by waxes containing a high proportion of lower melting fatty acids (berry, BW, and fruit wax, FW) required a comparatively higher Cg (6 and 7%wt, respectively), and in addition, these gels showed the lowest values for plateau elastic modulus (G'LVR) and a prominent crossover point at higher frequency. The gelation temperatures (TG'=G″) for all the studied gels were lower than room temperature, except for SFW and CRW. The yielding-type behavior of gels was evident, with most gels showing strong shear sensitivity and a weak thixotropic recovery. The rheological behavior was combined with the results of thermal analysis and microstructure studies (optical, polarized, and cryo-scanning electron microscopy) to explain the gelation properties of these waxes.

  16. Concentrations of veterinary drug residues in milk from individual farms in Croatia

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    Nina Bilandžić

    2011-09-01

    Full Text Available A total of 119 raw milk samples collected at individual small milk-producing facilities and collection tanks of milk routes from five counties of east and north continental Croatia were examined for chloramphenicol, sulfonamides, tetracyclines, gentamicin, streptomycin, dihydrostreptomycin, flumequine and enrofloxacin from January to March of 2011. Immunoassay methods used for drug determination were validated according to the guidelines laid down by European Commission Decision 2002/657/EC. Data indicated that the methods are appropriate for the detection of antibiotics measured. Measured mean values (μg L-1 of antibiotics were: 0.005 for chloramphenicol, 3.67 for sulfonamides, 2.83 for tetracyclines, 1.10 for gentamicin, 2.64 for streptomycin, 7.67 for dihydrostreptomycin, 10.4 for flumequine and 4.11 for enrofloxacin. None of samples analyzed showed the presence of veterinary drug residues above the maximum residues levels (MRLs established by European Union and Croatian legislation. The calculated estimated daily intakes (EDIs for the average daily milk consumption of 300 mL for an adult in Croatia for examined antibiotics showed levels 20 to 1640 times lower than the values of acceptable daily intakes (ADIs fixed by European Medicines Agency and World Health Organization. This suggested that toxicological risk associated with the consumption of analysed milk could not be considered a public health issue with regards to these veterinary drugs.

  17. Serum concentrations and profiles of polychlorinated biphenyls in Taiwan Yu-cheng victims twenty years after the incident

    Energy Technology Data Exchange (ETDEWEB)

    Lung, S.-C. Candice [Research Center for Environmental Changes, Academia Sinica, Nankang, Taipei, Taiwan 115 (China); Guo, Y.-L.L. [Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng-Li Rd., Tainan, Taiwan 70428 (China); Chang, H.-Y.[Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng-Li Rd., Tainan, Taiwan 70428 (China)]. E-mail: h7154@mail.ncku.edu.tw

    2005-07-15

    In 1979, about 2000 people in central Taiwan were intoxicated via rice oil consumption that was contaminated with polychlorinated biphenyls (PCBs). This 'Yu-cheng' incident was one of the two known major human PCB intoxication episodes. Twenty years after the intoxication, serum samples of 435 Yu-cheng victims, 414 adults and 21 children, were collected. Sixteen PCB congeners were analyzed with a gas chromatograph-electron capture detector. We found the median concentration of total PCBs in the adult serum was 1500 ng/g lipid, still substantially higher than that of the general population in Taiwan (3.7-fold) and most seafood consumers in the world. Most of analyzed PCB congeners in children were below or around the detection limits. Congener no. 138, however, had the highest concentrations, approximately accounting for 55% and 29% in the child and adult groups, respectively. Given that PCBs are persistent organic pollutants and endocrine disruptors, the concentrations and congener-specific profiles regarding the Yu-cheng victims provide valuable information for the investigation of such chemicals in humans. - Total serum PCBs in the Yu-cheng adult victims twenty years after the incident were still higher than that of the general population in Taiwan.

  18. Evaluating Oil and Gas Speciation Profiles with Factor Analysis of Ambient Volatile Organic Compound Concentrations in the Colorado Front Range

    Science.gov (United States)

    Capps, S.; Paranjothi, G.; Pierce, G. E.; Milford, J. B.

    2016-12-01

    Increased oil and gas (O&G) development, particularly through the use of hydraulic fracturing, in the Denver-Julesburg Basin (DJB) in Colorado over the last decade has been identified as a source of emissions of air pollutants, which are now included in chemical transport modeling. As one effort to evaluate its impact, ambient concentrations of volatile organic compounds (VOCs) that serve as precursors to ozone formation were measured in an Ozone Precursor Study conducted by the Colorado Department of Public Health and Environment during 2013 and 2014. The study included 6 - 9 a.m. measurements of an extensive suite of ozone-precursor VOCs from a site in an area of intensive O&G development in Platteville, CO, and another site in downtown Denver, CO. To evaluate the influences of urban activity or O&G development on these ambient concentrations, we used the U.S. EPA's Positive Matrix Factorization (PMF) tool. A five-factor PMF solution was selected as providing the best fit to the dataset comprised of VOC measurements for both years and both sites. One PMF factor matches the VOC emissions speciation profile for the flashing gas composition for condensate tanks in the DJB that was developed by the Western Regional Air Partnership for use in chemical transport modeling in the region. The contribution of this factor to individual and total VOC concentrations and ozone production reactivity is evaluated for Platteville and Denver.

  19. Sub-therapeutic nevirapine concentration during antiretroviral treatment initiation among children living with HIV: Implications for therapeutic drug monitoring.

    Directory of Open Access Journals (Sweden)

    Bindu Parachalil Gopalan

    Full Text Available Nevirapine, a component of antiretroviral therapy (ART in resource-limited settings, known for auto-induction of metabolism, is initiated at half therapeutic dose until day 14 ('lead-in period', and subsequently escalated to full dose. However, studies have shown that this dosing strategy based on adult studies may not be appropriate in children, given that younger children have higher drug clearance rates. In this prospective cohort study, we studied trough plasma nevirapine levels by high performance liquid chromatography (HPLC at days 7, 14 (lead-in period and 28 (full dose period after ART initiation amongst HIV-1 infected children initiating nevirapine-based ART in southern India. Among the 20 children (50% male, median age 9 years included in the study, sub-therapeutic trough plasma nevirapine concentration (<4μg/ml was seen in 65% (13/20 of children during the lead-in period within two weeks of ART initiation and among 10% of children at 4 weeks during full-dose nevirapine. Adherence was documented as ≥95% in all children by both caregiver self-report and pill count. Median nevirapine concentrations achieved at week 1 was 4.8 μg/ml, significantly lower than 8 μg/ml, the concentration achieved at week 4 (p = 0.034. Virological failure at one year of ART was observed in six children, and was not associated with median nevirapine concentration achieved during week 1, 2 or 4. We conclude that the dose escalation strategy currently practiced among young children living with HIV-1 resulted in significant subtherapeutic nevirapine concentration (≤4μg/ml during the lead-in period. We call for a closer look at pediatric-focused dosing strategies for nevirapine initiation in young children. Further studies to establish age-appropriate threshold nevirapine concentration are warranted in young children to corroborate the role of therapeutic drug monitoring in predicting virological outcome.

  20. Cost-effectiveness of routine measuring of serum drug concentrations and anti-drug antibodies in treatment of rheumatoid arthritis patients with TNF-α blockers

    Directory of Open Access Journals (Sweden)

    Laine J

    2016-04-01

    Full Text Available Juha Laine,1 T Sakari Jokiranta,2,3 Kari K Eklund,4,5 Merja Väkeväinen,1 Kari Puolakka6 1Pfizer Oy, Helsinki, 2United Medix Laboratories Ltd, Espoo, 3Research Programs Unit, Immunobiology, 4Department of Rheumatology, University of Helsinki, 5Helsinki University Central Hospital, Helsinki, 6Department of Medicine, South Karelia, Finland Abstract: Monitoring of anti-drug antibodies (ADAbs or serum concentrations of biologicals in treatment of rheumatoid arthritis could provide an explanation for a loss of efficacy and help in the choice of subsequent medication. Current clinical practices do not generally include such monitoring of tumor necrosis factor (TNF-α blockers on a routine basis. The main aims of this study were to estimate the probabilities of optimal and nonoptimal treatment decisions if infliximab or adalimumab drug trough level (DL and ADAbs are tested or not in rheumatoid arthritis, and to model cost-effectiveness of performing such monitoring on a routine basis. Data on DLs and ADAbs concentrations were obtained in Finland from clinically requested monitoring analyses of 486 and 1,137 samples from patients on adalimumab and infliximab, respectively. DL was within the target range in 42% of samples from adalimumab- and 50.4% of infliximab-treated patients. ADAbs were detected in approximately 20% and 13.5% of samples from adalimumab- and infliximab-treated patients, respectively. ADAbs were found in 52.3% and 41.3% of those with low adalimumab or infliximab DLs, respectively. The monitoring data were incorporated into probabilities for making the optimal treatment decision. Economic impact of clinical decision-making was modeled in a short-term (3–6 months scenario with 100 hypothetical patients. In the model, the combined measurement of DLs and ADAbs was cost-saving compared to the nontesting scenario when the monitoring results affected the treatment decision in at least 2–5 of 100 patients, a proportion which is easily

  1. Quantitative interpretation of Cl, Br and I porewater concentration profiles in lake sediments of Loch Lomond, Scotland

    International Nuclear Information System (INIS)

    Falck, W.E.; Hooker, P.J.

    1991-01-01

    One of the four natural analogue sites being investigated by the British Geological Survey is Loch Lomond, Scotland. Naturally occurring halogen elements (Cl, Br and I) have been migrating from a thin marine horizon into overlying freshwater deposits by a diffusion process which has been occurring for at least 5 400 years. This report summarizes the main findings accumulated since 1983 when the work was first begun, and provides a modelling interpretation of the measured concentration-depth profiles using a new numerical code called Diagen. The release rates of I and Br from the organic matter association in the shallow buried marine layer are very slow; subsequent anion movement by diffusion is affected by tortuosity differences in the sediments rather than by chemical reaction with the sediments. The bulk of the evidence supports conservative transport of iodide, bromide and chloride anions towards the sediment/loch interface. The report discusses some implications of the findings

  2. Comparison of Active Drug Concentrations in the Pulmonary Epithelial Lining Fluid and Interstitial Fluid of Calves Injected with Enrofloxacin, Florfenicol, Ceftiofur, or Tulathromycin.

    Directory of Open Access Journals (Sweden)

    Derek M Foster

    Full Text Available Bacterial pneumonia is the most common reason for parenteral antimicrobial administration to beef cattle in the United States. Yet there is little information describing the antimicrobial concentrations at the site of action. The objective of this study was to compare the active drug concentrations in the pulmonary epithelial lining fluid and interstitial fluid of four antimicrobials commonly used in cattle. After injection, plasma, interstitial fluid, and pulmonary epithelial lining fluid concentrations and protein binding were measured to determine the plasma pharmacokinetics of each drug. A cross-over design with six calves per drug was used. Following sample collection and drug analysis, pharmacokinetic calculations were performed. For enrofloxacin and metabolite ciprofloxacin, the interstitial fluid concentration was 52% and 78% of the plasma concentration, while pulmonary fluid concentrations was 24% and 40% of the plasma concentration, respectively. The pulmonary concentrations (enrofloxacin + ciprofloxacin combined exceeded the MIC90 of 0.06 μg/mL at 48 hours after administration. For florfenicol, the interstitial fluid concentration was almost 98% of the plasma concentration, and the pulmonary concentrations were over 200% of the plasma concentrations, exceeding the breakpoint (≤ 2 μg/mL, and the MIC90 for Mannheimia haemolytica (1.0 μg/mL for the duration of the study. For ceftiofur, penetration to the interstitial fluid was only 5% of the plasma concentration. Pulmonary epithelial lining fluid concentration represented 40% of the plasma concentration. Airway concentrations exceeded the MIC breakpoint for susceptible respiratory pathogens (≤ 2 μg/mL for a short time at 48 hours after administration. The plasma and interstitial fluid concentrations of tulathromcyin were lower than the concentrations in pulmonary fluid throughout the study. The bronchial concentrations were higher than the plasma or interstitial concentrations

  3. Comparison of Active Drug Concentrations in the Pulmonary Epithelial Lining Fluid and Interstitial Fluid of Calves Injected with Enrofloxacin, Florfenicol, Ceftiofur, or Tulathromycin

    Science.gov (United States)

    Foster, Derek M.; Martin, Luke G.; Papich, Mark G.

    2016-01-01

    Bacterial pneumonia is the most common reason for parenteral antimicrobial administration to beef cattle in the United States. Yet there is little information describing the antimicrobial concentrations at the site of action. The objective of this study was to compare the active drug concentrations in the pulmonary epithelial lining fluid and interstitial fluid of four antimicrobials commonly used in cattle. After injection, plasma, interstitial fluid, and pulmonary epithelial lining fluid concentrations and protein binding were measured to determine the plasma pharmacokinetics of each drug. A cross-over design with six calves per drug was used. Following sample collection and drug analysis, pharmacokinetic calculations were performed. For enrofloxacin and metabolite ciprofloxacin, the interstitial fluid concentration was 52% and 78% of the plasma concentration, while pulmonary fluid concentrations was 24% and 40% of the plasma concentration, respectively. The pulmonary concentrations (enrofloxacin + ciprofloxacin combined) exceeded the MIC90 of 0.06 μg/mL at 48 hours after administration. For florfenicol, the interstitial fluid concentration was almost 98% of the plasma concentration, and the pulmonary concentrations were over 200% of the plasma concentrations, exceeding the breakpoint (≤ 2 μg/mL), and the MIC90 for Mannheimia haemolytica (1.0 μg/mL) for the duration of the study. For ceftiofur, penetration to the interstitial fluid was only 5% of the plasma concentration. Pulmonary epithelial lining fluid concentration represented 40% of the plasma concentration. Airway concentrations exceeded the MIC breakpoint for susceptible respiratory pathogens (≤ 2 μg/mL) for a short time at 48 hours after administration. The plasma and interstitial fluid concentrations of tulathromcyin were lower than the concentrations in pulmonary fluid throughout the study. The bronchial concentrations were higher than the plasma or interstitial concentrations, with over 900

  4. Determination of safety margins for whole blood concentrations of alcohol and nineteen drugs in driving under the influence cases.

    Science.gov (United States)

    Kristoffersen, Lena; Strand, Dag Helge; Liane, Veronica Horpestad; Vindenes, Vigdis; Tvete, Ingunn Fride; Aldrin, Magne

    2016-02-01

    Legislative limits for driving under the influence of 20 non-alcohol drugs were introduced in Norway in February 2012. Per se limits corresponding to blood alcohol concentrations (BAC) of 0.2g/kg were established for 20 psychoactive drugs, and limits for graded sanctions corresponding to BACs of 0.5 and 1.2g/kg were determined for 13 of these drugs. This new legislation made it possible for the courts to make sentences based on the analytical results, similar to the situation for alcohol. To ensure that the reported concentration is as least as high as the true concentration, with a 99% safety level, safety margins had to be calculated for each of the substances. Diazepam, tetrahydrocannabinol (THC) and alcohol were used as model substances to establish a new model for estimating the safety margins. The model was compared with a previous used model established several years ago, by a similar yet much simpler model, and they were found to be in agreement. The measurement uncertainties depend on the standard batch used, the work list and the measurements' replicate. A Bayesian modelling approach was used to determine the parameters in the model, using a dataset of 4700 diazepam positive specimens and 5400 THC positive specimens. Different safety margins were considered for low and high concentration levels of diazepam (≤2μM (0.6mg/L) and >2μM) and THC (≤0.01μM (0.003mg/L) and >0.01μM). The safety margins were for diazepam 19.5% (≤2μM) and 34% (>2μM), for THC 19.5% (≤0.01μM) and 24.9% (>0.01μM). Concentration dependent safety margins for BAC were based on a dataset of 29500 alcohol positive specimens, and were in the range 10.4% (0.1g/kg) to 4.0% (4.0g/kg) at a 99% safety level. A simplified approach was used to establish safety margins for the compounds amphetamine, MDMA, methamphetamine, alprazolam, phenazepam, flunitrazepam, clonazepam, nitrazepam, oxazepam, buprenorphine, GHB, methadone, ketamine, cocaine, morphine, zolpidem and zopiclone. The

  5. Quinine unbound concentration is the best marker for therapeutic drug monitoring.

    Science.gov (United States)

    de Pablos-Martinez, Carlos; Porte, Lydie; Fraissinet, François; Berry, Antoine; Séraissol, Patrick; Lavit, Michel; Chatelut, Etienne; Concordet, Didier; Gandia, Peggy

    2016-10-01

    Quinine monitoring should be based on unbound concentration due to variable unbound fraction in malaria patients. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  6. Amino acid profile of metabolisable protein in lactating dairy cows is affected by dry matter concentration in grass-clover silage

    DEFF Research Database (Denmark)

    Johansen, Marianne; Lund, Peter; Weisbjerg, Martin Riis

    2018-01-01

    Our previous study showed that supply of metabolisable protein (MP) to lactating dairy cows increased with increasing dry matter (DM) concentration in grass-clover silage. The aim of this study was to examine how amino acid (AA) profile of MP was affected by silage DM concentration. Eight grass-c...

  7. Differential mechanism of Escherichia coli Inactivation by (+)-limonene as a function of cell physiological state and drug's concentration.

    Science.gov (United States)

    Chueca, Beatriz; Pagán, Rafael; García-Gonzalo, Diego

    2014-01-01

    (+)-limonene is a lipophilic antimicrobial compound, extracted from citrus fruits' essential oils, that is used as a flavouring agent and organic solvent by the food industry. A recent study has proposed a common and controversial mechanism of cell death for bactericidal antibiotics, in which hydroxyl radicals ultimately inactivated cells. Our objective was to determine whether the mechanism of Escherichia coli MG1655 inactivation by (+)-limonene follows that of bactericidal antibiotics. A treatment with 2,000 μL/L (+)-limonene inactivated 4 log10 cycles of exponentially growing E. coli cells in 3 hours. On one hand, an increase of cell survival in the ΔacnB mutant (deficient in a TCA cycle enzyme), or in the presence of 2,2'-dipyridyl (inhibitor of Fenton reaction by iron chelation), thiourea, or cysteamine (hydroxyl radical scavengers) was observed. Moreover, the ΔrecA mutant (deficient in an enzyme involved in SOS response to DNA damage) was more sensitive to (+)-limonene. Thus, this indirect evidence indicates that the mechanism of exponentially growing E. coli cells inactivation by 2,000 μL/L (+)-limonene is due to the TCA cycle and Fenton-mediated hydroxyl radical formation that caused oxidative DNA damage, as observed for bactericidal drugs. However, several differences have been observed between the proposed mechanism for bactericidal drugs and for (+)-limonene. In this regard, our results demonstrated that E. coli inactivation was influenced by its physiological state and the drug's concentration: experiments with stationary-phase cells or 4,000 μL/L (+)-limonene uncovered a different mechanism of cell death, likely unrelated to hydroxyl radicals. Our research has also shown that drug's concentration is an important factor influencing the mechanism of bacterial inactivation by antibiotics, such as kanamycin. These results might help in improving and spreading the use of (+)-limonene as an antimicrobial compound, and in clarifying the controversy about

  8. A pharmacodynamic analysis method to determine the relative importance of drug concentration and treatment time on effect.

    Science.gov (United States)

    Millenbaugh, N J; Wientjes, M G; Au, J L

    2000-01-01

    The pharmacodynamics of most drugs follow the empirical relationship, C(n) x T = h, where C is drug concentration, T is exposure time and h is drug exposure constant. The value of n indicates the relative importance of C and T in determining the effect. An n value greater than 1.0 indicates that for two infusions that produce the same C x T, a short infusion that delivers high concentrations over a short duration will produce a greater C(n) x T and therefore a greater effect, compared to a long infusion that delivers lower concentrations. The reverse is true for an n value less than 1.0 and would support the use of a slow infusion. Hence, it is important to determine the n values and whether the n value significantly differs from 1.0. This report describes a three-step method for this purpose. First, we obtained experimental data on the relationship between drug concentration, treatment time and effect, and analyzed the data with a three-dimensional surface response method to obtain the pharmacodynamic model parameters and the magnitude of data variability. The experiments used mitomycin C and two human cancer cell lines, i.e. bladder RT4 and pharynx FaDu cells. The n values obtained from four experiments ranged from 1.04 to 1.16 for FaDu cells and from 1.14 to 1.46 for RT4 cells. The variability in the effect data decreased from 11.9% at 0% effect to 6.14% at 100% effect. Second, these results were used with Monte Carlo simulations to generate 100 concentration-time-effect data sets, which contained randomly and normally distributed data variability comparable to the experimentally observed variability, for each experimentally determined n value. This is analogous to performing 100 experiments under the same experimental conditions. Third, we analyzed the simulated data sets to obtain 100 estimated n values. The frequency with which these estimated n values fell above or below 1.0 indicated the probability that the experimentally determined n value used in the

  9. A Profile of Drug Abuse in the United States. Volume I. Basic Report.

    Science.gov (United States)

    problem in three areas--law enforcement, education, and rehabilitation; and a projection of national trends over the next several years. It excludes consideration of alcohol abuse and drug abuse in the Armed Forces.

  10. Homeless drug users in Rotterdam, the Netherlands: profile, way of life, and the need for assistance.

    Science.gov (United States)

    Lempens, Ankie; van de Mheen, Dike; Barendregt, Cas

    2003-01-01

    Decreasing the number of homeless drug users is one of the main characteristics of inner city drugs policy. The present study selected an urban-ethnographic perspective (the subculture theory) in order to explore why one drug user is homeless and another 7 not, and to attempt to describe and define the homeless and their immediate social environment. These issues were formulated into the following research questions: 1. What are the sociodemographic characteristics of homeless drug users in Rotterdam, and do they differ from domiciled drug users? 2. What are their living conditions? 3. What are the reasons for being homeless? 4. Does the period of homelessness play a role in the need to change one's lifestyle? Five research methods were employed for this study: a literature search, interviews with key persons, field notes from community fieldworkers, a survey among drug users (n = 204), and photographic reports from six homeless users. Data were collected in 1998/1999. The results document that in our study population there were more women, more illegal persons, and more foreigners than among domiciled drug users, and that the homeless group used heroin and cocaine on more days. A large proportion of the homeless users had no identity papers and no health insurance. This did not, however, lead to more self-reported sickness or a higher prevalence of infectious diseases compared with nonhomeless drug users. Easily accessible (low threshold) social care centers and assistance are very important. Few of the homeless had voluntarily chosen a homeless life-most describe an event that was a trigger for their homelessness. The average duration of being homeless was 17 months, and the longer someone had been homeless the less inclined they were to change their situation. This paper also discusses policymaking implications.

  11. A risk profile of elite Australian athletes who use illicit drugs.

    Science.gov (United States)

    Dunn, Matthew; Thomas, Johanna O

    2012-01-01

    Much of the literature investigating the relationship between sports participation and substance use has focused upon student populations, with little focus being given to athletes who participate at elite levels. Identifying why some athletes may be at a greater risk for substance use can help in the design and implementation of prevention initiatives. Data for the current study was from 1684 self-complete surveys with elite Australian athletes. Eight percent (n=134) of the sample reported the use of at least one of the six illicit drugs under investigation (ecstasy, cannabis, cocaine, meth/amphetamine, ketamine and GHB) in the past year. Having been offered or having had the opportunity to use illicit drugs in the past year, knowing other athletes who use drugs and identifying as a 'full-time athlete' were significant predictors of past-year illicit drug use, while having completed secondary education or a post-school qualification was associated with a lower likelihood of past-year illicit drug use. Athletes are part of a sportsnet that includes family, coaches, support staff and other athletes, and these relationships may encourage the use, supply and demand for drugs. The current findings suggest that relationships with some of those in the sportsnet may play an important role when understanding illicit drug use among elite athletes. As education appears to be associated with a lower likelihood of illicit drug use among this group, initiatives should encourage athletes to engage in off-field pursuits which may also help prepare them for life after sport. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  12. Clinical and epidemiological profiles of individuals with drug-resistant tuberculosis

    Science.gov (United States)

    Pedro, Heloisa da Silveira Paro; Nardi, Susilene Maria Tonelli; Pereira, Maria Izabel Ferreira; Oliveira, Rosângela Siqueira; Suffys, Philip Noel; Gomes, Harrison Magdinier; Finardi, Amanda Juliane; de Moraes, Eloise Brasil; Baptista, Ida Maria Foschiani Dias; Machado, Ricardo Luiz Dantas; Castiglioni, Lilian

    2015-01-01

    Drug-resistant tuberculosis (TB) is a growing global threat. Approximately 450,000 people developed multidrug-resistant TB worldwide in 2012 and an estimated 170,000 people died from the disease. This paper describes the sociodemographic, clinical-epidemiological and bacteriological aspects of TB and correlates these features with the distribution of anti-TB drug resistance. Mycobacterium tuberculosis (MT) cultures and drug susceptibility testing were performed according to the BACTEC MGIT 960 method. The results demonstrated that MT strains from individuals who received treatment for TB and people who were infected with human immunodeficiency virus were more resistant to TB drugs compared to other individuals (p < 0.05). Approximately half of the individuals received supervised treatment, but most drug-resistant cases were positive for pulmonary TB and exhibited positive acid-fast bacilli smears, which are complicating factors for TB control programs. Primary healthcare is the ideal level for early disease detection, but tertiary healthcare is the most common entry point for patients into the system. These factors require special attention from healthcare managers and professionals to effectively control and monitor the spread of TB drug-resistant cases. PMID:25946248

  13. Drug profiling: a new scientific contribution to law enforcement operations in Viet Nam.

    Science.gov (United States)

    Hung, H M; Tien, N D; Truong, N X

    2005-01-01

    Since 1995 heroin sample comparisons have been carried out in Viet Nam to establish links between wholesalers and retailers. To that end, the physical and chemical characteristics of samples are analysed: their colour, the packaging material, including fingerprints, diacetylmorphine (heroin) content and the composition of some main alkaloids. At the beginning of 2002, having acquired expertise on impurity profiling and with the support of new instruments, the Institute of Forensic Sciences of Viet Nam introduced the routine impurity profiling of seized heroin and methamphetamine and later undertook to explain that process to national law enforcement bodies. Since then, 375 heroin and 29 methamphetamine samples have been analysed for major and minor impurities. Substances detected in the analysis of illicit heroin include diacetylmorphine, morphine, codeine, 06-monoacetylmorphine and acetylcodeine as well as adulterants such as paracetamol and caffeine. Since methamphetamine impurity profiling began, 29 samples have so far been analysed, and some samples have been grouped through the application of cluster analysis. In the case of heroin, impurity profiling has established a link between two major trafficking groups suspected of obtaining heroin from the same source of production. Analysis has also revealed a link between one wholesaler and several retailers in one region. In addition, impurity profiling provides new information on the preparation and production of some methamphetamine and fake Ecstasy tablets.

  14. Estimation of suspended sediment concentration from Acoustic Doppler Current Profiler (ADCP) instrument: A case study of Lembeh Strait, North Sulawesi

    Science.gov (United States)

    Dwinovantyo, Angga; Manik, Henry M.; Prartono, Tri; Susilohadi; Ilahude, Delyuzar

    2017-01-01

    Measurement of suspended sediment concentration (SSC) is one of the parameters needed to determine the characteristics of sediment transport. However, the measurement of SSC nowadays still uses conventional technique and it has limitations; especially in temporal resolution. With advanced technology, the measurement can use hydroacoustic technology such as Acoustic Doppler Current Profiler (ADCP). ADCP measures the intensity of backscatter as echo intensity unit from sediment particles. The frequency of ADCP used in this study was 400 kHz. The samples were measured and collected from Lembeh Strait, North Sulawesi. The highest concentration of suspended sediment was 98.89 mg L-1 and the lowest was 45.20 mg L-1. Time series data showed the tidal condition affected the SSC. From the research, we also made correction from sound signal losses effect such as spherical spreading and sound absorption to get more accurate results by eliminating these parameters in echo intensity data. Simple linear regression analysis at echo intensity measured from ADCP to direct measurement of SSC was performed to obtain the estimation of the SSC. The comparison result of estimation of SSC from ADCP measurements and SSC from laboratory analyses was insignificantly different based on t-test statistical analysis with 95% confidence interval percentage.

  15. Determination of the vertical profile of particle number concentration adjacent to a motorway using an unmanned aerial vehicle.

    Science.gov (United States)

    Villa, T F; Jayaratne, E R; Gonzalez, L F; Morawska, L

    2017-11-01

    A quantitative assessment of the vertical profile of traffic pollution, specifically particle number concentration (PNC), in an open space adjacent to a motorway was possible for the first time, to the knowledge of the authors, using an Unmanned Aerial Vehicle (UAV) system. Until now, traffic pollution has only been measured at ground level while the vertical distribution, is limited to studies conducted from buildings or fixed towers and balloons. This new UAV system demonstrated that the PNC sampled during the period form 10 a.m. to 4 p.m., outside the rush hours with a constant traffic flow, increased from a concentration of 2 × 10 4 p/cm 3 near the ground up to 10 m, and then sharply decreased attaining a steady value of 4 × 10 3 p/cm 3 beyond a height of about 40 m. While more comprehensive investigations would be warranted under different conditions, such as topography and vehicle and fuel type, this finding is of great significance, given that it demonstrates the impact of traffic emissions on human exposure, but less so to pollution within the upper part of the boundary layer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Serum Adiponectin and Leptin Concentrations in Relation to Body Fat Distribution, Hematological Indices and Lipid Profile in Humans

    Directory of Open Access Journals (Sweden)

    Anna Lubkowska

    2015-09-01

    Full Text Available The purpose of the study was to evaluate the relationship between serum adiponectin and leptin concentrations and body composition, hematological indices and lipid profile parameters in adults. The study involved 95 volunteers (BMI from 23.3 to 53 kg/m2. Anthropometric parameters were measured: body weight and height, waist and hip circumference, waist-to-hip ratio, body fat mass (BMF, subcutaneous and visceral fat mass (SFM, VFM, lean body mass (LBM, skeletal muscle mass (SMM. In serum we determined adiponectin and leptin concentrations, extracellular hemoglobin, total bilirubin, as well as lipid metabolism (TCh, HDL-Ch, LDL-Ch, TG. Mean adipokine levels were significantly higher in women (p ≤ 0.01, adiponectin significantly negatively correlated with body height and weight, systolic blood pressure and absolute LBM and SMM values. The same relation was observed for erythroid system indicators and lipid indicators. A positive correlation was exceptionally found between adiponectin and HDL-Ch. LEP negatively correlated with some percentage rates (%LBM, %SMM. Only in women, we observed a positive correlation between LEP and body weight, BMI and WHR. Studies on ADPN and the ADPN/LEP ratio as a valuable complementary diagnostic element in the prediction and prevention of cardiovascular diseases need to be continued.

  17. Drug concentrations in the serum and cerebrospinal fluid of patients treated with norvancomycin after craniotomy.

    Science.gov (United States)

    Wu, Y; Kang, J; Wang, Q

    2017-02-01

    Intracranial infection by gram-positive cocci is commonly found after craniotomy. Norvancomycin was independently developed in China, and had demonstrated therapeutic capability against gram-positive infection. This study investigated the serum and cerebrospinal fluid (CSF) concentrations in patients that received intravenous injection of norvancomycin after craniotomy. Patients with an indwelling catheter in the operational area/ventricle after craniotomy were administered norvancomycin by two approaches: (1) The conventional group consisted of 14 cases that were infused with 0.8 g norvancomycin for 1 h, every 12 h; (2) The continuous administration group consisted of 14 cases that were infused with 0.8 g norvancomycin for 1 h, and then another 0.4 g for 11 h with extended infusion, followed by continuous infusion of 0.4 g norvancomycin for 12 h. Samples of serum and CSF were collected at different time-points to measure norvancomycin levels after administration. In the conventional and continuous administration groups, the peak serum concentrations of norvancomycin were 55.52 ± 26.04 and 59.22 ± 41.88 mg/L, respectively, while those at 24 h were 8.21 ± 6.04 and 8.01 ± 4.17 mg/L, respectively. Meanwhile, peak CSF concentrations were 16.31 ± 11.15 and 8.82 ± 8.91 mg/L, respectively, while those at 24 h were 6.12 ± 2.34 and 6.24 ± 4.38 mg/L, respectively. This preliminary study showed that for the early administration of standard doses of norvancomycin post-neurosurgery, the CSF concentration in both the conventional and continuous administration groups reached or exceeded the 90 % minimum inhibitory concentration (MIC 90 , 2 mg/L) of target bacteria such as methicillin-resistant Staphylococcus aureus (MRSA).

  18. Molecular characterization and drug susceptibility profile of a Mycobacterium avium subspecies avium isolate from a dog with disseminated infection.

    Science.gov (United States)

    Armas, Federica; Furlanello, Tommaso; Camperio, Cristina; Trotta, Michele; Novari, Gianluca; Marianelli, Cinzia

    2016-01-12

    Mycobacterium avium complex (MAC) infections have been described in many mammalian species including humans and pets. We isolated and molecularly typed the causative agent of a rare case of disseminated mycobacteriosis in a dog. We identified the pathogen as a M. avium subspecies avium by sequencing the partial genes gyrB and rpsA. Considering the zoonotic potential of this infection, and in an attempt to ensure the most effective treatment for the animal, we also determined the drug susceptibility profile of the isolate to the most common drugs used to treat MAC disease in humans. The pathogen was tested in vitro against the macrolide clarithromycin, as well as against amikacin, ciprofloxacin, rifampicin, ethambutol and linezolid by the resazurin microdilution assay. It was found to be sensitive to all tested drugs save ethambutol. Despite the fact that the pathogen was sensitive to the therapies administered, the dog's overall clinical status worsened, and the animal died shortly after antimicrobial susceptibility results became available. Nucleotide sequencing of the embB gene, the target gene most commonly associated with ethambutol resistance, showed new missense mutations when compared to sequences available in public databases. In conclusion, we molecularly identified the MAC pathogen and determined its drug susceptibility profile in a relatively short period of time (seven days). We also characterized new genetic mutations likely to have been involved in the observed ethambutol resistance. Our results confirm the usefulness of both the gyrB and the rpsA genes as biomarkers for an accurate identification and differentiation of MAC pathogens.

  19. Polysubstance use in cannabis users referred for treatment: Drug use profiles, psychiatric comorbidity and cannabis-related beliefs

    Directory of Open Access Journals (Sweden)

    Jason Paul Connor

    2013-08-01

    Full Text Available Background: Population-based surveys demonstrate cannabis users are more likely to use both illicit and licit substances, compared with non-cannabis users. Few studies have examined the substance use profiles of cannabis users referred for treatment. Coexisting mental health symptoms and underlying cannabis-related beliefs associated with these profiles remains unexplored.Methods: Comprehensive drug use and dependence severity (Severity of Dependence Scale- Cannabis [SDS-C] data were collected on a sample of 826 cannabis users referred for treatment. Patients completed the General Health Questionnaire (GHQ-28, Cannabis Expectancy Questionnaire (CEQ, and Cannabis Refusal Self-Efficacy Questionnaire (CRSEQ and Positive Symptoms and Manic-Excitement subscales of the Brief Psychiatric Rating Scale (BPRS. Latent class analysis (LCA was performed on last month use of drugs to identify patterns of multiple drug use. Mental health comorbidity and cannabis beliefs were examined by identified drug use pattern.Results: A three-class solution provided the best fit to the data- (1 Cannabis and tobacco users (n = 176, (2 Cannabis, tobacco, and alcohol users (n = 498, and (3 wide-ranging substance users (n = 132. Wide-ranging substance users (3 reported higher levels of cannabis dependence severity, negative cannabis expectancies, lower opportunistic and emotional relief self-efficacy, higher levels of depression and anxiety, and higher manic-excitement and positive psychotic symptoms.Conclusion: In a sample of cannabis users referred for treatment, wide-ranging substance use was associated with elevated risk on measures of cannabis dependence, comorbid psychopathology and dysfunctional cannabis cognitions. These findings have implications for cognitive-behavioural assessment and treatment.

  20. Differential profiles of drug-addicted patients according to gender and the perpetration of intimate partner violence.

    Science.gov (United States)

    Arteaga, Alfonso; López-Goñi, José J; Fernández-Montalvo, Javier

    2015-10-01

    This study explored the differential profiles of drug-addicted patients according to gender and the perpetration of intimate partner violence (IPV). The study assessed a sample of 127 drug-addicted patients (84 male and 43 female) who sought treatment. Information about socio-demographic and consumption characteristics, IPV, psychopathological symptoms, personality characteristics and maladjustment variables was obtained. Four groups were created according to gender and the presence or absence of the perpetration of IPV: (a) men with IPV (n=41), (b) women with IPV (n=29), (c) men without IPV (n=43), and (d) women without IPV (n=14). The four groups were compared in terms of all of studied variables. There were significant differences between the groups in the severity of the addiction and personality characteristics. In general, the drug-addicted patients with associated IPV perpetration exhibited greater scores for nearly all of the studied variables, independent of gender. Moreover, the differences among groups were more strongly related to perpetration of IPV than to the gender of the patients. According to the results obtained, treatment programs for drug addiction are a suitable context for identifying the presence of IPV, but IPV is typically unnoticed in addiction treatment programs. The implications of these results for future research and clinical practice are discussed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Germline genetic predictors of aromatase inhibitor concentrations, estrogen suppression and drug efficacy and toxicity in breast cancer patients.

    Science.gov (United States)

    Hertz, Daniel L; Henry, N Lynn; Rae, James M

    2017-04-01

    The third-generation aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, are highly effective for the treatment of estrogen receptor-positive breast cancer in postmenopausal women. AIs inhibit the aromatase (CYP19A1)-mediated production of estrogens. Most patients taking AIs achieve undetectable blood estrogen concentrations resulting in drug efficacy with tolerable side effects. However, some patients have suboptimal outcomes, which may be due, in part, to inherited germline genetic variants. This review summarizes published germline genetic associations with AI treatment outcomes including systemic AI concentrations, estrogenic response to AIs, AI treatment efficacy and AI treatment toxicities. Significant associations are highlighted with commentary about prioritization for future validation to identify pharmacogenetic predictors of AI treatment outcomes that can be used to inform personalized treatment decisions in patients with estrogen receptor-positive breast cancer.

  2. Potential life-threatening variations of drug concentrations in intravenous infusion systems: potassium chloride, insulin, and heparin

    Energy Technology Data Exchange (ETDEWEB)

    Bergman, N.; Vellar, I.D.

    1982-09-18

    The investigation of concentrations of active agents in common carrier media for intravenous infusion revealed that potassium chloride tends to form a pool when it is added without mixing to carrier media in glass or polyvinyl chloride (PVC) containers which are already suspended in their functional position with ports pointing downwards. Heparin behaves in a similar fashion when added without mixing to carrier media in PVC containers. Such uneven distribution may expose a patient to potentially dangerous, possibly lethal, concentrations of a drug even when a relatively small amount of it is used. Insulin floats to the top of a Haemaccel container if its contents are not adequately mixed after addition of insulin. The resultant irregularity of insulin dosage may make the management of diabetic ketoacidosis more difficult. It is recommended that the instructions for the adequate mixing of contents should appear on all containers of carrier media for intravenous infusions.

  3. Interdependence of initial cell density, drug concentration and exposure time revealed by real-time impedance spectroscopic cytotoxicity assay

    DEFF Research Database (Denmark)

    Caviglia, Claudia; Zor, Kinga; Canepa, Silvia

    2015-01-01

    We investigated the combined effect of the initial cell density (12 500, 35 000, 75 000, and 100 000 cells cm−2) and concentration of the anti-cancer drug doxorubicin on HeLa cells by performing timedependent cytotoxicity assays using real-time electrochemical impedance spectroscopy. A correlation...... between the rate of cell death and the initial cell seeding density was found at 2.5 μM doxorubicin concentration, whereas this was not observed at 5 or 100 μM. By sensing the changes in the cell–substrate interaction using impedance spectroscopy under static conditions, the onset of cytotoxicity...... was observed 5 h earlier than when using a standard colorimetric end-point assay (MTS) which measures changes in the mitochondrial metabolism. Furthermore, with the MTS assay no cytotoxicity was observed after 15 h of incubation with 2.5 μM doxorubicin, whereas the impedance showed at this time point cell...

  4. Significant interaction between activated charcoal and antiretroviral therapy leading to subtherapeutic drug concentrations, virological breakthrough and development of resistance.

    Science.gov (United States)

    Tseng, Alice L; la Porte, Charles; Salit, Irving E

    2013-01-01

    A 42-year-old, treatment-experienced woman, virologically suppressed on tenofovir/emtricitabine and boosted atazanavir, experienced virological breakthrough, drop in CD4(+) T-cell count and undetectable drug concentrations. Adherence to treatment was confirmed, but repeat testing yielded similar results. After 2 months, the patient stated that she had been taking activated charcoal to manage gastrointestinal symptoms associated with her combination antiretroviral therapy, but she had recently discontinued the charcoal. Atazanavir concentrations were therapeutic but the patient's viral load rebounded and genotype testing revealed new reverse transcriptase mutations. The patient was changed to zidovudine, lamivudine, and boosted darunavir and achieved viral suppression. At 1 year follow-up, her viral load remained activated charcoal and atazanavir/ritonavir leading to virological breakthrough and development of resistance.

  5. Drug metabolism: Comparison of biodistribution profile of holmium in three different compositions in healthy Wistar rats

    International Nuclear Information System (INIS)

    Cerqueira-Coutinho, Cristal; Vidal, Lluis Pascual; Pinto, Suyene Rocha; Santos-Oliveira, Ralph

    2016-01-01

    Radioisotope holmium is a candidate to be used in cancer treatment and diagnosis. There are different holmium salts and they present distinct solubility and consequently different biodistribution profiles. In this work, we aimed to evaluate the biodistribution profiles of two holmium salts (chloride and sulfate) and holmium nanoparticles (oxide) through an in vivo biodistribution assay using animal model. Samples were labeled with technetium-99m and administered in Wistar rats by retro-orbital route. Holmium chloride is highly soluble in water and it was quickly filtered by the kidneys while holmium sulfate that presents lower solubility in water was mainly found in the liver and the spleen. However, both the salts showed a similar biodistribution profile. On the other hand, holmium oxide showed a very different biodistribution profile since it seemed to interact with all organs. Due to its particle size range (approximately 100 nm) it was not intensively filtered by the kidneys being found in high quantities in many organs, for this reason its use as a nanoradiopharmaceutical could be promising in the oncology field. - Highlights: • This article brings the biodistribution of holmium in 3 different compositions. • The results, as a technical note may help other researchers around the world to elucidate the mechanism (biological behavior) and the best strategy to use holmium as radiopharmaceutical.

  6. Comparison of concentrations of two proteinase inhibitors, porcine pancreatic elastase inhibitory capacity, and cell profiles in sequential bronchoalveolar lavage samples.

    Science.gov (United States)

    Morrison, H M; Kramps, J A; Dijkman, J H; Stockley, R A

    1986-01-01

    Bronchoalveolar lavage is used to obtain cells and proteins from the lower respiratory tract for diagnosis and research. Uncertainity exists about which site in the lung is sampled by the lavage fluid and what effect different lavage volumes have on recovery of the constituents of lavage fluid. Dilution of alveolar lining fluid by lavage fluid is variable and results are usually expressed as protein ratios to surmount this problem. We have compared cell profiles and the concentrations of two proteinase inhibitors--the low molecular weight bronchial protease inhibitor antileucoprotease and alpha 1 proteinase inhibitor, together with alpha 1 proteinase inhibitor function and its relationship to the cell profile in sequential bronchoalveolar lavage fluid samples from patients undergoing bronchoscopy. There was no difference in total or differential cell counts or albumin or alpha 1 proteinase inhibitor concentrations between the first and second halves of the lavage. Both the concentration of antileucoprotease and the ratio of antileucoprotease to albumin were, however, lower in the second half of the lavage (2p less than 0.01 and 2p less than 0.05 respectively). There was no difference in the function of alpha 1 proteinase inhibitor (assessed by inhibition of porcine pancreatic elastase--PPE) between aliquots (0.28 mole PPE inhibited/mol alpha 1 proteinase inhibitor; range 0-1.19 for the first half and 0.37 mol PPE inhibited/mol alpha 1 proteinase inhibitor; range 0.10-0.80 for the second half). About 60-70% of alpha 1 proteinase inhibitor in each half of the lavage fluid was inactive as an inhibitor. The function of alpha 1 proteinase inhibitor did not differ between bronchitic smokers and ex-smokers. Alpha 1 proteinase inhibitor function was not related to the number of total white cells, macrophages, or neutrophils in the lavage fluid. Contamination of lavage by red blood cells was found to alter the concentration of alpha 1 proteinase inhibitor but not its

  7. A novel doxorubicin-loaded in situ forming gel based high concentration of phospholipid for intratumoral drug delivery.

    Science.gov (United States)

    Wu, Wenqi; Chen, Hui; Shan, Fengying; Zhou, Jing; Sun, Xun; Zhang, Ling; Gong, Tao

    2014-10-06

    The purpose of this study was to develop a safe and effective drug delivery system for local chemotherapy. A novel injectable in-situ-forming gel system was prepared using small molecule materials, including phospholipids, medium chain triglycerides (MCTs), and ethanol. Thus, this new sustained release system was named PME (first letter of phospholipids, MCT, and ethanol). PME has a well-defined molecule structure, a high degree of safety, and better biocompatible characteristics. It was in sol state with low viscosity in vitro and turned into a solid or semisolid gel in situ after injection. When loaded with doxorubicin (Dox), PME-D (doxorubicin-loaded PME) exhibited notably antitumor efficiency in S180 sarcoma tumors bearing mice after a single intratumoral injection. In vitro, PME-D had remarkable antiproliferative efficacies against MCF-7 breast cancer cells for over 5 days. Moreover, the initial burst effect can hardly be observed from PME system, which was different from many other in-situ-forming gels. The in vivo biodistribution study showed the high Dox concentration in tumors compared with other major organs after PME-D intratumoral administration. The strong signal in tumors was retained for more than 14 days after one single injection. The high concentration of Dox in tumor and long-term retention may explain the superior therapeutic efficacy and reduced side effects. The PME-D in-situ-forming gel system is a promising drug delivery system for local chemotherapy.

  8. Preparation of sustained release co-extrudates by hot-melt extrusion and mathematical modelling of in vitro/in vivo drug release profiles.

    Science.gov (United States)

    Quintavalle, U; Voinovich, D; Perissutti, B; Serdoz, F; Grassi, G; Dal Col, A; Grassi, M

    2008-03-03

    Aim of this work was to develop a cylindrical co-extrudate characterised by an in vivo sustained release profile by means of a hot-melt extrusion process. Co-extrudate was made up of two concentric extruded matrices: an inner one having a hydrophilic character, based on polyethylene glycol, and an outer one with lipophilic character, based on microcrystalline wax. Both segments contained theophylline as a model drug. A screening between several devices differing for dimensions (diameter and length) and relative proportions of the inner and outer part was carried out on the basis of their in vitro drug release and the release mechanism was studied by means of a mathematical model. The co-extrudate exhibiting the desired sustained release was selected for in vivo bioavailability studies. In vivo studies confirmed the achievement of the purpose of the research, demonstrating the desired release of theophylline on four healthy volunteers. Accordingly, hot-melt extrusion process is a viable method to produce in a single step co-extrudates showing a sustained release. In addition, the developed mathematical model proved to be a reliable descriptor of the both in vitro and in vivo experimental data.

  9. Cytostatic versus cytocidal profiling of quinoline drug combinations via modified fixed-ratio isobologram analysis

    Science.gov (United States)

    2013-01-01

    Background Drug combination therapy is the frontline of malaria treatment. There is an ever-accelerating need for new, efficacious combination therapies active against drug resistant malaria. Proven drugs already in the treatment pipeline, such as the quinolines, are important components of current combination therapy and also present an attractive test bank for rapid development of new concepts. Methods The efficacy of several drug combinations versus chloroquine-sensitive and chloroquine-resistant strains was measured using both cytostatic and cytocidal potency assays. Conclusions These screens identify quinoline and non-quinoline pairs that exhibit synergy, additivity, or antagonism using the fixed-ratio isobologram method and find tafenoquine – methylene blue combination to be the most synergistic. Also, interestingly, for selected pairs, additivity, synergy, or antagonism defined by quantifying IC50 (cytostatic potency) does not necessarily predict similar behaviour when potency is defined by LD50 (cytocidal potency). These data further support an evolving new model for quinoline anti-malarials, wherein haem and haemozoin are the principle target for cytostatic activity, but may not be the only target relevant for cytocidal activity. PMID:24044530

  10. Addiction research centres and the nurturing of creativity: National Drug Dependence Treatment Centre, India--a profile.

    Science.gov (United States)

    Ray, Rajat; Dhawan, Anju; Chopra, Anita

    2013-10-01

    The National Drug Dependence Treatment Centre (NDDTC) is a part of the All India Institute of Medical Sciences, a premier autonomous medical university in India. This article provides an account of its origin and its contribution to the field of substance use disorder at the national and international levels. Since its establishment, the NDDTC has played a major role in the development of various replicable models of care, the training of post-graduate students of psychiatry, research, policy development and planning. An assessment of the magnitude of drug abuse in India began in the early 1990s and this was followed by a National Survey on Extent, Patterns and Trends of Drug Abuse in 2004. Several models of clinical care have been developed for population subgroups in diverse settings. The centre played an important role in producing data and resource material which helped to scale up opioid substitution treatment in India. A nationwide database on the profile of patients seeking treatment (Drug Abuse Monitoring System) at government drug treatment centres has also been created. The centre has provided valuable inputs for the Government of India's programme planning. Besides clinical studies, research has also focused on pre-clinical studies. Capacity-building is an important priority, with training curricula and resource material being developed for doctors and paramedical staff. Many of these training programmes are conducted in collaboration with other institutions in the country. The NDDTC has received funding from several national and international organizations for research and scientific meetings, and, most recently (2012), it has been designated as a World Health Organization Collaborating Centre on Substance Abuse. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

  11. Genetic diversity and drug resistance profiles in HIV type 1- and HIV type 2-infected patients from Cape Verde Islands.

    Science.gov (United States)

    Oliveira, Vânia; Bártolo, Inês; Borrego, Pedro; Rocha, Cheila; Valadas, Emília; Barreto, Jorge; Almeida, Elsa; Antunes, Francisco; Taveira, Nuno

    2012-05-01

    Our aim was to characterize for the first time the genetic diversity of HIV in Cape Verde Islands as well as the drug resistance profiles in treated and untreated patients. Blood specimens were collected from 41 HIV-1 and 14 HIV-2 patients living in Santiago Island. Half of the patients were on antiretroviral treatment (ART). Pol and env gene sequences were obtained using in-house methods. Phylogenetic analysis was used for viral subtyping and the Stanford Algorithm was used for resistance genotyping. For HIV-1, the amplification of pol and env was possible in 27 patients (66%). HIV-1 patients were infected with subtypes G (13, 48%), B (2, 7%), F1 (2, 7%), and CRF02_AG (2, 7%), and complex recombinant forms including a new C/G variant (n=8, 30%). Drug resistance mutations were detected in the PR and RT of three (10%) treated patients. M41L and K103N transmitted drug resistance mutations were found in 2 of 17 (12%) untreated patients. All 14 HIV-2 isolates belonged to group A. The origin of 12 strains was impossible to determine whereas two strains were closely related to the historic ROD strain. In conclusion, in Cape Verde there is a long-standing HIV-2 epidemic rooted in ROD-like strains and a more recent epidemic of unknown origin. The HIV-1 epidemic is caused by multiple subtypes and complex recombinant forms. Drug resistance HIV-1 strains are present at moderate levels in both treated and untreated patients. Close surveillance in these two populations is crucial to prevent further transmission of drug-resistant strains.

  12. Early pharmaceutical profiling to predict oral drug absorption: current status and unmet needs.

    Science.gov (United States)

    Bergström, Christel A S; Holm, René; Jørgensen, Søren Astrup; Andersson, Sara B E; Artursson, Per; Beato, Stefania; Borde, Anders; Box, Karl; Brewster, Marcus; Dressman, Jennifer; Feng, Kung-I; Halbert, Gavin; Kostewicz, Edmund; McAllister, Mark; Muenster, Uwe; Thinnes, Julian; Taylor, Robert; Mullertz, Anette

    2014-06-16

    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 pharmaceutical profiling methods available, with focus on in silico and in vitro models typically used to forecast active pharmaceutical ingredient's (APIs) in vivo performance after oral administration. An overview of the composition of human, animal and simulated gastrointestinal (GI) fluids is provided 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 are discussed in detail and future demands on pharmaceutical profiling are identified. It is expected that innovative computational and experimental methods that better describe molecular processes involved in vivo during dissolution and absorption of APIs will be developed in the OrBiTo. These methods will provide early insights into successful pathways (medicinal chemistry or formulation strategy) and are anticipated to increase the number of new APIs with good oral absorption being discovered. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. In vitro dissolution profile study of mucolytic drug ambroxol hydrochloride from solid oral dosage form by UHPLC-MS/MS

    Directory of Open Access Journals (Sweden)

    Vujović Maja M.

    2017-01-01

    Full Text Available In this paper a simplified dissolution test was performed for the release of ambroxol from tablets according to the European Pharmacopoeia. In vitro, three different dissolution media; 0.1 M HCl pH 1.2, acetate buffer (ABS pH 4.5 and phosphate buffer (PBS pH 6.8 were used for the simulation of the gastrointestinal conditions at temperature of 37.0±0.5°C. The drug release was evaluated by a new ultra - high performance liquid chromatography (UHPLC - tandem mass spectrometry (MS/MS method. The method was validated to meet requirements as per ICH guidelines which include linearity, specificity, precision, accuracy and robustness. The corresponding dissolution profiles showed more than 80% drug release within 30 minutes without significant differences. Further, the developed and validated UHPLC-MS/MS method could find a useful application in the process of production, quality control and bioavailability/bioequivalence studies of new pharmaceutical formulations of drugs in order to achieve a safe therapeutic efficacy. [Projekat Ministarstva nauke Republike Srbije, br. 175045

  14. Evaluation of air jet erosion profiles in metal mesh supported SCR plate catalyst based on glass fiber concentrations

    Science.gov (United States)

    Rajath, S.; Nandakishora, Y.; Siddaraju, C.; Roy, Sukumar

    2018-04-01

    This paper explains the evaluation of erosion profiles in metal mesh supported SCR plate catalyst structures in which the glass fibers concentration in the catalyst material is considered as prime factor for erosion resistance and mechanical strength. The samples are prepared and tested at the specified and constant conditions like velocity as 30m/s, sand flow rate as 2g/min, average particle diameter 300 µm and all these samples were tested at different angles at impact preferably 15°,30°,45°,60°,75°,and 90° as per ASTM G76 standards. Say, if 5% glass fibers are present in catalyst material, then erosion resistance increases, but the density of glass fibers is very less because each glass fiber is approximately 20 microns in diameter and weight of individual is negligible. The composition in which 2% fiber is present has slightly higher erosion comparatively, but 3% glass fibers or more foreign inclusion like excessive binders can be eliminated that contributes much for the conversion of NOx. So 2% -3% glass fibers are preferred and optimized based on NOx conversion and erosion resistance property.

  15. HIV-1 subtypes and drug resistance profiles in a cohort of heterosexual patients in Istanbul, Turkey.

    Science.gov (United States)

    Köksal, Muammer Osman; Beka, Hayati; Lübke, Nadine; Verheyen, Jens; Eraksoy, Haluk; Cagatay, Atahan; Kaiser, Rolf; Akgül, Baki; Agacfidan, Ali

    2015-08-01

    Turkey is seeing a steady rise in rates of HIV infection in the country. The number of individuals with HIV/AIDS was greater than 7000 in 2014 according to data released by the Ministry of Health, and heterosexual contacts were reported to be the main transmission routes. Istanbul has the highest number of reported cases of HIV infection. The aim of the study was to determine the prevalence of HIV-1 drug resistance in 50 heterosexual patients from Istanbul. The most prevalent subtype was found to be subtype B (56.2 %). Resistance-associated mutations were found in 14 patients with 6/14 patients being therapy-experienced and 8/14 therapy naive at the time point of analysis. With increasing number of patients who require treatment and the rapid up-scaling of the antiretroviral therapy in Turkey, HIV-1 drug resistance testing is recommended before starting treatment in order to achieve better clinical outcomes.

  16. Serum concentrations of psychotropic drugs in neonates as a PROgnOstic Factor for admission to the neonatology ward and withdrawal symptoms: PROOF-1.

    Science.gov (United States)

    Sparla, Shirley C A; Coppens, Hans; Evers, Inge M; Stramrood, Claire A I; Pasker-de Jong, Pieternel C M; van der Westerlaken, Monique M L; Hogeman, Paul H G; Malingré, Mirte M

    2017-05-01

    The aim is to determine whether serum drug concentrations obtained from the neonate's umbilical cord can be used as a prognostic factor for admission to the neonatology ward and the occurrence of withdrawal symptoms. A retrospective observational monocenter cohort study was carried out among pregnant women using psychotropic drugs and their baby. Binary logistic regression was used for the multivariate analysis. Of the 186 neonates included, 22.6% (n=42) were admitted to the neonatology ward, 6.5% (n=12) because of withdrawal. Among women with therapeutic concentrations of psychotropic medication, 22.0% (n=5) of the neonates had withdrawal symptoms. When comparing neonates with therapeutic versus undetectable drug concentrations, an odds ratio of 3.1 (95% confidence interval: 1.1-8.6) was found for admission to the neonatology ward and an odds ratio of 20.5 (95% confidence interval: 2.2-186.1) for the occurrence of withdrawal symptoms. Therapeutic concentrations of psychotropic drugs in neonates' umbilical cord blood correspond with higher odds for admission to the neonatology ward and the occurrence of withdrawal symptoms compared with neonates with undetectable drug concentrations. The measurement of drug concentrations in the neonate may contribute toward the general clinical assessment of the physician to predict the necessity of admission to the neonatology ward and the risk of withdrawal symptoms.

  17. Effects of four different antihypertensive drugs on plasma metabolomic profiles in patients with essential hypertension.

    Directory of Open Access Journals (Sweden)

    Timo P Hiltunen

    Full Text Available In order to search for metabolic biomarkers of antihypertensive drug responsiveness, we measured >600 biochemicals in plasma samples of subjects participating in the GENRES Study. Hypertensive men received in a double-blind rotational fashion amlodipine, bisoprolol, hydrochlorothiazide and losartan, each as a monotherapy for one month, with intervening one-month placebo cycles.Metabolomic analysis was carried out using ultra high performance liquid chromatography-tandem mass spectrometry. Full metabolomic signatures (the drug cycles and the mean of the 3 placebo cycles became available in 38 to 42 patients for each drug. Blood pressure was monitored by 24-h recordings.Amlodipine (P values down to 0.002, bisoprolol (P values down to 2 x 10-5 and losartan (P values down to 2 x 10-4 consistently decreased the circulating levels of long-chain acylcarnitines. Bisoprolol tended to decrease (P values down to 0.002 the levels of several medium- and long-chain fatty acids. Hydrochlorothiazide administration was associated with an increase of plasma uric acid level (P = 5 x 10-4 and urea cycle metabolites. Decreases of both systolic (P = 0.06 and diastolic (P = 0.04 blood pressure after amlodipine administration tended to associate with a decrease of plasma hexadecanedioate, a dicarboxylic fatty acid recently linked to blood pressure regulation.Although this systematic metabolomics study failed to identify circulating metabolites convincingly predicting favorable antihypertensive response to four different drug classes, it provided accumulating evidence linking fatty acid metabolism to human hypertension.

  18. A novel experimental design method to optimize hydrophilic matrix formulations with drug release profiles and mechanical properties.

    Science.gov (United States)

    Choi, Du Hyung; Lim, Jun Yeul; Shin, Sangmun; Choi, Won Jun; Jeong, Seong Hoon; Lee, Sangkil

    2014-10-01

    To investigate the effects of hydrophilic polymers on the matrix system, an experimental design method was developed to integrate response surface methodology and the time series modeling. Moreover, the relationships among polymers on the matrix system were studied with the evaluation of physical properties including water uptake, mass loss, diffusion, and gelling index. A mixture simplex lattice design was proposed while considering eight input control factors: Polyethylene glycol 6000 (x1 ), polyethylene oxide (PEO) N-10 (x2 ), PEO 301 (x3 ), PEO coagulant (x4 ), PEO 303 (x5 ), hydroxypropyl methylcellulose (HPMC) 100SR (x6 ), HPMC 4000SR (x7 ), and HPMC 10(5) SR (x8 ). With the modeling, optimal formulations were obtained depending on the four types of targets. The optimal formulations showed the four significant factors (x1 , x2 , x3 , and x8 ) and other four input factors (x4 , x5 , x6 , and x7 ) were not significant based on drug release profiles. Moreover, the optimization results were analyzed with estimated values, targets values, absolute biases, and relative biases based on observed times for the drug release rates with four different targets. The result showed that optimal solutions and target values had consistent patterns with small biases. On the basis of the physical properties of the optimal solutions, the type and ratio of the hydrophilic polymer and the relationships between polymers significantly influenced the physical properties of the system and drug release. This experimental design method is very useful in formulating a matrix system with optimal drug release. Moreover, it can distinctly confirm the relationships between excipients and the effects on the system with extensive and intensive evaluations. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  19. Prevalence and differential profile of patients with drug addiction problems who commit intimate partner violence.

    Science.gov (United States)

    Arteaga, Alfonso; Fernández-Montalvo, Javier; López-Goñi, José J

    2015-12-01

    The objectives of this study were, first, to explore the prevalence of aggressors with lifetime intimate partner violence (IPV) among patients in the Proyecto Hombre of Navarra (Spain) addiction treatment programme; and second, to know the specific and differential characteristics of patients presenting IPV as aggressors. A sample of 162 patients (119 men and 43 women) was assessed. Data on socio-demographic and substance consumption characteristics, IPV variables, psychopathological symptoms, and personality variables were obtained. The profiles of patients in addiction treatment with and without a history of violence towards their partners were compared. The results showed that 33.6% of people in treatment for addiction had committed violence against their partners. This prevalence was significantly higher (χ(2)  = 15.6, p < .001) in women (63.3%) than in men (24.2%). In the 98.4% of the cases the IPV was bidirectional. Patients with a history of IPV perpetration showed greater severity in substance consumption variables, psychopathological symptoms, and personality traits. Gender, the family scale on the European version of the Addiction Severity Index (EuropASI), and the aggressive-sadistic scale on the Millon Clinical Multiaxial Inventory (MCMI-III) were the main variables related to the presence of IPV as aggressors. There was a differential profile in patients with IPV perpetration, showing more psychopathological and personality symptoms. Moreover, in this study being a woman was one of the main predictors of committing IPV. © American Academy of Addiction Psychiatry.

  20. Maternal grazing on stubble and Mediterranean shrubland improves meat lipid profile in light lambs fed on concentrates.

    Science.gov (United States)

    Mateo, L; Delgado, P; Ortuño, J; Bañón, S

    2017-12-04

    Concentrates-fed lamb meat is often associated with an unfavourable lipid profile (high levels of saturated and/or n-6 polyunsaturated fatty acids; SFA and PUFA). For this reason, Spanish sheep producers from Mediterranean areas are turning to traditional grazing by ewes to obtain healthier lamb meat. The objective of this research was to determine the effects of maternal grazing on the fatty acid (FA) composition of weaned lamb meat. The ewes (Segureña breed) were allocated to two different rearing systems during pregnancy (5 months) and lactation (45 days): (i) feeding indoors on barley grain and lucerne pellets; (ii) grazing on cereal stubble, fallow land and seasonal pastures consisting of Mediterranean shrubs, herbs and trees. Two groups of 20 autumn and spring lambs were sampled. The lambs were weaned at 13.1±0.9 kg and 45.0±4.1 days age and fed on grain-based concentrates until they reached 24.8±2.1 kg live weight (light lambs slaughtered at 98.3±3.6 days of age). The FA content was determined in the intramuscular loin fat by gas chromatography using a flame ionization detector. The ewe diet did not affect the levels of the main lamb FAs (C18:1c+t, C16:0 and C18:2c), and so did not provide any additional reduction in fat saturation. Saturated fatty acids represented around 40% of total FAs determined in the meat. Ewe grazing acted as an n-3 PUFA-promoting diet, providing a lamb meat with a lower n-6/n-3 ratio. Spring lamb meat had higher proportions of n-3 PUFA (C18:3n-3, C20:5, C22:5 and C22:6) and conjugated linoleic acid (C18:2c9t11+c11t9) to the detriment of the n-6 PUFAs (C20:4, C20:2 and C22:4), while autumn lamb meat also had higher levels of C18:3n-3 and C18:3n-6, and lower level of C20:4, which points to little seasonal differences. The n-6/n-3 ratio achieved by ewe grazing fell from 8.2 to 4.1 (Spring) and from 7.6 to 5.5 (Autumn), values which are close to those recommended in human diet for good cardiovascular health. These n-6/n-3

  1. Quantification of Hydrogen Concentrations in Surface and Interface Layers and Bulk Materials through Depth Profiling with Nuclear Reaction Analysis.

    Science.gov (United States)

    Wilde, Markus; Ohno, Satoshi; Ogura, Shohei; Fukutani, Katsuyuki; Matsuzaki, Hiroyuki

    2016-03-29

    Nuclear reaction analysis (NRA) via the resonant (1)H((15)N,αγ)(12)C reaction is a highly effective method of depth profiling that quantitatively and non-destructively reveals the hydrogen density distribution at surfaces, at interfaces, and in the volume of solid materials with high depth resolution. The technique applies a (15)N ion beam of 6.385 MeV provided by an electrostatic accelerator and specifically detects the (1)H isotope in depths up to about 2 μm from the target surface. Surface H coverages are measured with a sensitivity in the order of ~10(13) cm(-2) (~1% of a typical atomic monolayer density) and H volume concentrations with a detection limit of ~10(18) cm(-3) (~100 at. ppm). The near-surface depth resolution is 2-5 nm for surface-normal (15)N ion incidence onto the target and can be enhanced to values below 1 nm for very flat targets by adopting a surface-grazing incidence geometry. The method is versatile and readily applied to any high vacuum compatible homogeneous material with a smooth surface (no pores). Electrically conductive targets usually tolerate the ion beam irradiation with negligible degradation. Hydrogen quantitation and correct depth analysis require knowledge of the elementary composition (besides hydrogen) and mass density of the target material. Especially in combination with ultra-high vacuum methods for in-situ target preparation and characterization, (1)H((15)N,αγ)(12)C NRA is ideally suited for hydrogen analysis at atomically controlled surfaces and nanostructured interfaces. We exemplarily demonstrate here the application of (15)N NRA at the MALT Tandem accelerator facility of the University of Tokyo to (1) quantitatively measure the surface coverage and the bulk concentration of hydrogen in the near-surface region of a H2 exposed Pd(110) single crystal, and (2) to determine the depth location and layer density of hydrogen near the interfaces of thin SiO2 films on Si(100).

  2. Effects of forage type, forage to concentrate ratio, and crushed linseed supplementation on milk fatty acid profile in lactating dairy cows

    NARCIS (Netherlands)

    Sterk, A.R.; Johansson, B.E.O.; Taweel, H.Z.H.; Murphy, M.; Vuuren, van A.M.; Hendriks, W.H.; Dijkstra, J.

    2011-01-01

    The effects of an increasing proportion of crushed linseed (CL) in combination with varying forage type (grass or corn silage) and forage to concentrate ratio (F:C), and their interactions on milk fatty acid (FA) profile of high-producing dairy cows was studied using a 3-factor Box-Behnken design.

  3. Mycobacterium tuberculosis Complex Genotype Diversity and Drug Resistance Profiles in a Pediatric Population in Mexico

    Directory of Open Access Journals (Sweden)

    Mercedes Macías Parra

    2011-01-01

    Full Text Available The aim of this study was to determine the frequency of drug resistance and the clonality of genotype patterns in M. tuberculosis clinical isolates from pediatric patients in Mexico (n=90 patients from 19 states; time period—January 2002 to December 2003. Pulmonary disease was the most frequent clinical manifestation (71%. Children with systemic tuberculosis (TB were significantly younger compared to patients with localized TB infections (mean 7.7±6.2 years versus 15±3.4 years P=0.001. Resistance to any anti-TB drug was detected in 24/90 (26.7% of the isolates; 21/90 (23.3% and 10/90 (11.1% were resistant to Isoniazid and Rifampicin, respectively, and 10/90 (11.1% strains were multidrug-resistant (MDR. Spoligotyping produced a total of 55 different patterns; 12/55 corresponded to clustered isolates (n=47, clustering rate of 52.2%, and 43/55 to unclustered isolates (19 patterns were designated as orphan by the SITVIT2 database. Database comparison led to designation of 36 shared types (SITs; 32 SITs (n=65 isolates matched a preexisting shared type in SITVIT2, whereas 4 SITs (n=6 isolates were newly created. Lineage classification based on principal genetic groups (PGG revealed that 10% of the strains belonged to PGG1 (Bovis and Manu lineages. Among PGG2/3 group, the most predominant clade was the Latin-American and Mediterranean (LAM in 27.8% of isolates, followed by Haarlem and T lineages. The number of single drug-resistant (DR and multidrug-resistant (MDR-TB isolates in this study was similar to previously reported in studies from adult population with risk factors. No association between the spoligotype, age, region, or resistance pattern was observed. However, contrary to a study on M. tuberculosis spoligotyping in Acapulco city that characterized a single cluster of SIT19 corresponding to the EAI2-Manila lineage in 70 (26% of patients, not a single SIT19 isolate was found in our pediatric patient population. Neither did we find any

  4. Bacterial microbiota profiling in gastritis without Helicobacter pylori infection or non-steroidal anti-inflammatory drug use.

    Directory of Open Access Journals (Sweden)

    Xiao-Xing Li

    Full Text Available Recent 16S ribosomal RNA gene (rRNA molecular profiling of the stomach mucosa revealed a surprising complexity of microbiota. Helicobacter pylori infection and non-steroidal anti-inflammatory drug (NSAID use are two main contributors to gastritis and peptic ulcer. However, little is known about the association between other members of the stomach microbiota and gastric diseases. In this study, cloning and sequencing of the 16S rRNA was used to profile the stomach microbiota from normal and gastritis patients. One hundred and thirty three phylotypes from eight bacterial phyla were identified. The stomach microbiota was found to be closely adhered to the mucosa. Eleven Streptococcus phylotypes were successfully cultivated from the biopsies. One to two genera represented a majority of clones within any of the identified phyla. We further developed two real-time quantitative PCR assays to quantify the relative abundance of the Firmicutes phylum and the Streptococcus genus. Significantly higher abundance of the Firmicutes phylum and the Streptococcus genus within the Firmicutes phylum was observed in patients with antral gastritis, compared with normal controls. This study suggests that the genus taxon level can largely represent much higher taxa such as the phylum. The clinical relevance and the mechanism underlying the altered microbiota composition in gastritis require further functional studies.

  5. Inhibition of EGF Uptake by Nephrotoxic Antisense Drugs In Vitro and Implications for Preclinical Safety Profiling

    Directory of Open Access Journals (Sweden)

    Annie Moisan

    2017-03-01

    Full Text Available Antisense oligonucleotide (AON therapeutics offer new avenues to pursue clinically relevant targets inaccessible with other technologies. Advances in improving AON affinity and stability by incorporation of high affinity nucleotides, such as locked nucleic acids (LNA, have sometimes been stifled by safety liabilities related to their accumulation in the kidney tubule. In an attempt to predict and understand the mechanisms of LNA-AON-induced renal tubular toxicity, we established human cell models that recapitulate in vivo behavior of pre-clinically and clinically unfavorable LNA-AON drug candidates. We identified elevation of extracellular epidermal growth factor (EGF as a robust and sensitive in vitro biomarker of LNA-AON-induced cytotoxicity in human kidney tubule epithelial cells. We report the time-dependent negative regulation of EGF uptake and EGF receptor (EGFR signaling by toxic but not innocuous LNA-AONs and revealed the importance of EGFR signaling in LNA-AON-mediated decrease in cellular activity. The robust EGF-based in vitro safety profiling of LNA-AON drug candidates presented here, together with a better understanding of the underlying molecular mechanisms, constitutes a significant step toward developing safer antisense therapeutics.

  6. [Drug registries: post-marketing evaluation of the benefit-risk profile and promotion of appropriateness. The regional point of view].

    Science.gov (United States)

    Martelli, Luisa; Venegoni, Mauro

    2013-06-01

    Italian Regions and the Italian regulatory agency share a common interest in promoting the appropriateness of drug use, containing drug expenditure and acquiring additional evidence on the effectiveness and safety of drugs. Drug registries can help attaining these objectives. Specifically, the registries implemented in Italy were able to cover the first two objectives, whereas some critical issues were raised on the third one. For instance, the data recorded in the registries are not available at regional level to conduct safety and effectiveness investigations. This is a paradox, when considering that drugs included in the registries have a risk-benefit profile that is only partially defined at the moment of marketing. Currently, researchers and regions can conduct epidemiological research (cohort and case control studies), on the basis of record-linkage procedures, on all drugs prescribed in general practice (which are older drugs with a better defined risk-benefit profile). The expected outcomes of registries should be more clearly defined: when the main aim is to promote appropriateness, the recording of only a very limited amount of data should be required (to avoid a bureaucratic burden on clinicians).The Italian centers of the ENCePP network might play an important role in planning and conducting drug registries: through the presence in the steering committees of the registries, and in conducting epidemiological studies that make the most of this powerful instrument.

  7. Institutional profile: the national Swedish academic drug discovery & development platform at SciLifeLab.

    Science.gov (United States)

    Arvidsson, Per I; Sandberg, Kristian; Sakariassen, Kjell S

    2017-06-01

    The Science for Life Laboratory Drug Discovery and Development Platform (SciLifeLab DDD) was established in Stockholm and Uppsala, Sweden, in 2014. It is one of ten platforms of the Swedish national SciLifeLab which support projects run by Swedish academic researchers with large-scale technologies for molecular biosciences with a focus on health and environment. SciLifeLab was created by the coordinated effort of four universities in Stockholm and Uppsala: Stockholm University, Karolinska Institutet, KTH Royal Institute of Technology and Uppsala University, and has recently expanded to other Swedish university locations. The primary goal of the SciLifeLab DDD is to support selected academic discovery and development research projects with tools and resources to discover novel lead therapeutics, either molecules or human antibodies. Intellectual property developed with the help of SciLifeLab DDD is wholly owned by the academic research group. The bulk of SciLifeLab DDD's research and service activities are funded from the Swedish state, with only consumables paid by the academic research group through individual grants.

  8. Chemical profiling of the genome with anti-cancer drugs defines target specificities.

    Science.gov (United States)

    Pang, Baoxu; de Jong, Johann; Qiao, Xiaohang; Wessels, Lodewyk F A; Neefjes, Jacques

    2015-07-01

    Many anticancer drugs induce DNA breaks to eliminate tumor cells. The anthracycline topoisomerase II inhibitors additionally cause histone eviction. Here, we performed genome-wide high-resolution mapping of chemotherapeutic effects of various topoisomerase I and II (TopoI and II) inhibitors and integrated this mapping with established maps of genomic or epigenomic features to show their activities in different genomic regions. The TopoI inhibitor topotecan and the TopoII inhibitor etoposide are similar in inducing DNA damage at transcriptionally active genomic regions. The anthracycline daunorubicin induces DNA breaks and evicts histones from active chromatin, thus quenching local DNA damage responses. Another anthracycline, aclarubicin, has a different genomic specificity and evicts histones from H3K27me3-marked heterochromatin, with consequences for diffuse large B-cell lymphoma cells with elevated levels of H3K27me3. Modifying anthracycline structures may yield compounds with selectivity for different genomic regions and activity for different tumor types.

  9. Method optimization for drug impurity profiling in supercritical fluid chromatography: Application to a pharmaceutical mixture.

    Science.gov (United States)

    Muscat Galea, Charlene; Didion, David; Clicq, David; Mangelings, Debby; Vander Heyden, Yvan

    2017-12-01

    A supercritical chromatographic method for the separation of a drug and its impurities has been developed and optimized applying an experimental design approach and chromatogram simulations. Stationary phase screening was followed by optimization of the modifier and injection solvent composition. A design-of-experiment (DoE) approach was then used to optimize column temperature, back-pressure and the gradient slope simultaneously. Regression models for the retention times and peak widths of all mixture components were built. The factor levels for different grid points were then used to predict the retention times and peak widths of the mixture components using the regression models and the best separation for the worst separated peak pair in the experimental domain was identified. A plot of the minimal resolutions was used to help identifying the factor levels leading to the highest resolution between consecutive peaks. The effects of the DoE factors were visualized in a way that is familiar to the analytical chemist, i.e. by simulating the resulting chromatogram. The mixture of an active ingredient and seven impurities was separated in less than eight minutes. The approach discussed in this paper demonstrates how SFC methods can be developed and optimized efficiently using simple concepts and tools. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Decline and changing profile of hepatitis delta among injection drug users in Spain.

    Science.gov (United States)

    Aguilera, Antonio; Trastoy, Rocio; Barreiro, Pablo; Costa, José Javier; de Mendoza, Carmen; Peña, Jose M; Soriano, Vicente

    2018-01-01

    Roughly 15 million people worldwide have hepatitis delta, the most severe form of chronic viral hepatitis that often leads to cirrhosis and liver cancer. Injection drug users (IDUs) are the largest HDV reservoir. Their resurgence in North America and Europe may represent a new opportunity for HDV to spread more widely. We examined all consecutive active IDUs seen for the first time and enrolled in detoxification programmes at two clinics in Spain during two periods (1993-1996 and 2011-2014, respectively). Serum markers of HIV, HBV and HDV infection were tested. A total of 209 IDUs were examined in the first period. Mean age was 27-years-old. All had markers of past or current HBV infection. The rate of HIV-antibody (Ab), hepatitis B surface antigen (HBsAg) and HDV-Ab was as follows: 122 (58.4%), 73 (34.9%) and 62 (29.7%), respectively. Serum HDV-Ab was recognized in 53.4% of HBsAg+ and 16.9% of HBsAg- patients (Pforeign immigrants. It may reflect the benefit of universal HBV vaccination as well as the success of needle exchange programmes in Spain.

  11. 1.6 μm DIAL Measurement and Back Trajectory Analysis of CO2 Concentration Profiles in the Lower-Atmosphere

    Science.gov (United States)

    Shibata, Y.; Nagasawa, C.; Abo, M.

    2016-12-01

    Carbon dioxide (CO2) is the primary greenhouse gas emitted through human activities. In addition to the ground level CO2 network, vertical CO2 concentration profiles also play an important role for the estimation of the carbon budget and global warming in the inversion method. Especially, for the detailed analysis of forest carbon dynamics and CO2 fluxes of urban area, vertical CO2 concentration profiles with high spatial and temporal resolution in the lower atmosphere have been conducted by a differential absorption lidar (DIAL). We have observed several vertical profiles of CO2 concentrations for nighttime and daytime from 0.25 to 2.5 km altitude with range resolution of 300 m and integration time of 1 hour. In order to extract information on the origin of the CO2 masses, one day back trajectories were calculated by using a three dimensional (3-D) atmospheric transport model. In many cases, CO2 low concentration layers of over 1.5km altitude were flown by westerly winds from the forest. In another case, high concentration layers of CO2 were flown from the urban areas. As the spectra of absorption lines of any molecules are influenced basically by the temperature in the atmosphere, laser beams of three wavelengths around a CO2 absorption spectrum are transmitted alternately to the atmosphere for simultaneous measurements of CO2 concentration and temperature profiles. Moreover, a few processing algorithms of CO2-DIAL are also performed for improvement of measurement accuracy. For computation of trajectories and drawing their figures, the JRA-25 data provided by the cooperative research project for the JRA-25 long-term reanalysis of the Japan Meteorological Agency (JMA) and the Central Research Institute of Electric Power Industry (CRIEPI) and the NIPR trajectory model (Tomikawa and Sato, 2005; http://firp-nitram.nipr.ac.jp) were used. This work was financially supported by the System Development Program for Advanced Measurement and Analysis of the Japan Science and

  12. Certain hormonal profiles of postpartum anestrus jersey crossbred cows treated with controlled internal drug release and ovsynch protocol

    Directory of Open Access Journals (Sweden)

    Dayanidhi Jena

    2016-10-01

    Full Text Available Aim: The study was conducted to determine the serum levels of certain hormones in post-partum anestrus cows following treatment with controlled internal drug release (CIDR and Ovsynch protocol. Materials and Methods: A total of 30 postpartum anestrus cows were divided into three equal groups after thorough gynecoclinical examination. The Group 1 animals received an intravaginal progesterone device on day 0 and 2 ml of prostaglandin F2α (PGF2α on day of CIDR removal (7th day, Group 2 cows were treated with ovsynch protocol (gonadotropinreleasing hormone [GnRH]-PGF2α-GnRH on day 0, 7 and 9, respectively, and Group 3 cows were supplemented with mineral mixture and treated as control. The serum estrogen, progesterone, triiodothyronine, and thyroxine concentration were estimated using enzyme-linked immunosorbent assay kit and absorbance was read at 450 nm with Perkin Elmer Wallac 1420 Microplate Reader. Results: There was a significant increase in progesterone level in Group 1 after withdrawal of CIDR as compared to other two groups. However, the estrogen assay revealed a greater concentration in Group 2 against Group 1 on day 7 of sampling. However, there was no significant difference for serum triiodothyronine (T3 and thyroxine (T4 irrespective of treatment protocols and days of sampling. Conclusion: Treatment with CIDR based progesterone therapy and drug combinations may affect the reproductive hormonal balance like estrogen and progesterone, which is inevitable for successful return to cyclicity and subsequent fertilization and conception. However, as far as serum T3 and T4 concentration concerned it may not give an astounding result.

  13. Lipid profile of rheumatoid arthritis patients treated with anti-tumor necrosis factor-alpha drugs changes according to disease activity and predicts clinical response.

    Science.gov (United States)

    Cacciapaglia, Fabio; Anelli, Maria Grazia; Rinaldi, Angela; Serafino, Lucia; Covelli, Michele; Scioscia, Crescenzio; Iannone, Florenzo; Lapadula, Giovanni

    2014-11-01

    Patients with active rheumatoid arthritis (RA) frequently show an atherogenic lipid profile, which has been linked with the inflammatory reaction. Inflammatory cytokines, and particularly tumor necrosis factor-alpha (TNF-α), are implicated in the pathogenesis of both atherosclerosis and RA, and also involved in the development of the impaired lipid profile detected in active RA. Although anti-TNF-α agents have been proven effective in controlling joint damage and systemic inflammation, controversy remains about the effect of these drugs on the lipid profile; therefore, the aim of our study was to investigate the effect of anti-TNF-α treatment, in combination with disease-modifying anti-rheumatic drugs (DMARDs) and corticosteroid therapy, on the lipid profile of patients with active RA. Our data suggest that the combination anti-TNF-α/DMARDs/steroids do not significantly interfere with the lipid profile of RA patients. However, analysis of clinical response data showed that patients achieving low disease activity or remission seem to have a protective lipid profile, suggesting that better control of inflammation and disease activity can affect lipid metabolism. The available evidence indicates that high inflammation interferes with lipid metabolism, whereas good control of the chronic inflammatory state may positively influence the lipid profile and cardiovascular risk. Low cholesterol levels at baseline could predict a favorable outcome with anti-TNF-α treatment, but these data need to be confirmed by large prospective studies with long-term follow-up. © 2014 Wiley Periodicals, Inc.

  14. Tacrolimus concentration/dose ratio as a therapeutic drug monitoring strategy: The influence of gender and comedication

    Directory of Open Access Journals (Sweden)

    Rančić Nemanja

    2015-01-01

    Full Text Available Background/Aim. A combination of tacrolimus and other drugs such as corticosteroids has been commonly used immunosuppresive regimens. On the other hand, there is a growing body of evidence that male and female may differ in their response to the equal drug treatment. The aim of the study was to estimated the use of tacrolimus concentration/dose (C/D ratio for the assessment of the influence of gender differences and comedication on tacrolimus exposure in renal transplant recipients. Methods. This prospective case series study included 54 patients, in which the unit of monitoring was outpatient examination (1,872 of the renal transplant patients. The patients were monitored in the period 2010-2014, starting one month after the transplantation. Tacrolimus trough concentrations (TTC were measured by chemiluminescence microparticles immunoassay. Results. TTC and the tacrolimus C/D ratio were significantly lower in the females comparing with the males. Contrary to the males, in the females a significant increase of the tacrolimus daily dose (TDD per body weight and TTC, along with the corticosteroid dose increase, was not accompanied by any significant changes in the tacrolimus C/D ratio; in different corticosteroid doses faster elimination of tacrolimus was found with the exception of the doses > 0.25 mg/kg. In the patients treated with proton pump inhibitors, mainly with pantoprazole TDD per body weight and TTC were significantly higher, while the tacrolimus C/D ratio was significantly lower compared to the patients without this treatment. In the patients treated with calcium channel blockers, TDD per body weight was significantly lower (particularly with amlodipine while the tacrolimus C/D ratio was higher compared to the patients who were not treated by them. Conclusion. A lower tacrolimus exposure was detected in females in comparison to males. When gender differences were considered in the context of different corticosteroid doses, faster

  15. Formulation Optimization of Sustained-Release Ammonio Methacrylate Copolymer Microspheres. Effects of Log P and Concentration of Polar Cosolvents, and Role of the Drug/Copolymer Ratio

    Directory of Open Access Journals (Sweden)

    Piroska Szabó-Révész

    2011-11-01

    Full Text Available The objectives of this work were the formulation optimization of the preparation process parameters and to evaluate spray-dried sustained-release microspheres using ammonio methacrylate copolymer (AMC as a polymer matrix. The effects of log P and the concentrations of the cosolvents (acetone, methyl ethyl ketone and n-butyl acetate and different drug/copolymer ratios as independent variables on the physicochemical parameters (the W1/O emulsion viscosity, the microsphere production yield, the average particle size, the encapsulation efficiency and the cumulative in vitro drug release as dependent variables were studied. The optimization was carried out on the basis of the 33 factorial design study. The optimization process results showed that addition of polar cosolvents proved effective, linear relationships were observed between the independent and the dependent variables. The best conditions were achieved by microspheres prepared by using a low/medium cosolvent log P, cosolvent concentration of 25–50% v/v and a drug/copolymer ratio of 1:16. The microspheres ensured sustained release with Nernst and Baker-Lonsdale release profiles.

  16. Experimental evaluation of the Continuous Risk Profile (CRP) approach to the current Caltrans methodology for high collision concentration location identification.

    Science.gov (United States)

    2012-03-01

    This report evaluates the performance of Continuous Risk Profile (CRP) compared with the : Sliding Window Method (SWM) and Peak Searching (PS) methods. These three network : screening methods all require the same inputs: traffic collision data and Sa...

  17. Considerations for automated machine learning in clinical metabolic profiling: Altered homocysteine plasma concentration associated with metformin exposure.

    Science.gov (United States)

    Orlenko, Alena; Moore, Jason H; Orzechowski, Patryk; Olson, Randal S; Cairns, Junmei; Caraballo, Pedro J; Weinshilboum, Richard M; Wang, Liewei; Breitenstein, Matthew K

    2018-01-01

    With the maturation of metabolomics science and proliferation of biobanks, clinical metabolic profiling is an increasingly opportunistic frontier for advancing translational clinical research. Automated Machine Learning (AutoML) approaches provide exciting opportunity to guide feature selection in agnostic metabolic profiling endeavors, where potentially thousands of independent data points must be evaluated. In previous research, AutoML using high-dimensional data of varying types has been demonstrably robust, outperforming traditional approaches. However, considerations for application in clinical metabolic profiling remain to be evaluated. Particularly, regarding the robustness of AutoML to identify and adjust for common clinical confounders. In this study, we present a focused case study regarding AutoML considerations for using the Tree-Based Optimization Tool (TPOT) in metabolic profiling of exposure to metformin in a biobank cohort. First, we propose a tandem rank-accuracy measure to guide agnostic feature selection and corresponding threshold determination in clinical metabolic profiling endeavors. Second, while AutoML, using default parameters, demonstrated potential to lack sensitivity to low-effect confounding clinical covariates, we demonstrated residual training and adjustment of metabolite features as an easily applicable approach to ensure AutoML adjustment for potential confounding characteristics. Finally, we present increased homocysteine with long-term exposure to metformin as a potentially novel, non-replicated metabolite association suggested by TPOT; an association not identified in parallel clinical metabolic profiling endeavors. While warranting independent replication, our tandem rank-accuracy measure suggests homocysteine to be the metabolite feature with largest effect, and corresponding priority for further translational clinical research. Residual training and adjustment for a potential confounding effect by BMI only slightly modified

  18. The effect of excessive disodium ethylene diamine tetraacetic acid (Na2EDTA anticoagulant concentration on leukocytes profile in peripheral blood examination

    Directory of Open Access Journals (Sweden)

    Usi Sukorini

    2007-09-01

    Full Text Available Accuracy of leukocytes profile assessment is influenced by several pre analytical factors, among others, the anticoagulant concentration. EDTA is one of the most frequently used anticoagulant in peripheral blood examination. Several references stated that inappropriate concentration of EDTA anticoagulant in blood sample may affect the result of leukocytes profile in peripheral blood examination. The aim of this study was to evaluate whether there are differences among leukocytes profile in peripheral blood examination specimens, which were prepared with excessive Na2EDTA anticoagulant in different concentration. This study was conducted in Faculty of Medicine, Gadjah Mada University. Blood samples from 30 subjects were taken using vein puncture. Two millimeters blood was divided into 4 Na2EDTA-containing tubes. Before that, one drop of blood without Na2EDTA anticoagulant was used to make blood film right after vein puncture, as control. Each tubes contained different concentration of anticoagulant. The first tube contained Na2EDTA in standard concentration 2 mg/ml; the remaining tubes contained 4 mg/ml, 6 mg/ml, and 8 mg/ml respectively. These samples were immediately examined using SYSMEX SE-9500 automatic cell counter to measure the total and differential leukocytes count; and were stained with Wright staining for morphological examination under the microscope. These procedures were done before 20 minutes of vein puncture. There were significant decrement of total leukocytes count, absolute differential leukocytes count and monocyte percentage following excessive Na2EDTA administration. Neutrophil percentage was found to be relatively increased and the difference was significant. Lymphocyte, eosinophil and basophil percentages were not significantly different. Morphological examination showed significant increment in irregular cytoplasm margin, vacoulation and irregular nuclei lobes following excessive Na2EDTA administration. It is concluded

  19. Mixed solvency concept in reducing surfactant concentration of self-emulsifying drug delivery systems of candesartan cilexetil using D-optimal mixture design

    OpenAIRE

    Chandna Chandan; R K Maheshwari

    2013-01-01

    The objective of this present study was to explore the utility of "mixed solvency" concept to enhance the solubility of poorly-water soluble drug, candesartan cilexetil (CC) in modified solubilizer system. The objective of this paper is to reduce the surfactant concentration traditionally involved in the formulation of self-emulsifying drug delivery systems (SEDDS) by proposing an alternate system of solubilizer to provide novel surfactant/cosurfactant system, to aid traditionally involved co...

  20. The effects of excessive disodium ethylene diamine tetraacetic acid (Na2EDTA anticoagulant concentration toward hematology profile and morphology of erythrocytes in peripheral blood examination

    Directory of Open Access Journals (Sweden)

    Tri Ratnaningsih

    2006-09-01

    Full Text Available The purpose of this study is to know whether there are differences between hematology profile and morphology of erythrocytes of blood specimens which are prepared with excessive Na2EDTA anticoagulant in different concentration. This study was conducted in Faculty of Medicine Gadjah Mada University. The criteria of subject were male, age from 18 until 22 years old and healthy, ascertained from history taking and vital sign examination. Blood samples from 33 subjects were taken using vein puncture. Two millimeters blood was divided into 4 Na2EDTA-containing tubes. Before that, one drop of blood without Na2EDTA anticoagulant was used for making control blood film right after vein puncture. Each tubes contained different concentration of anticoagulant. The first tube contained Na2EDTA in standard concentration 2 mg/dl; the remaining tubes contained consecutively, 4 mg/dl, 6 mg/dl, and 8 mg/dl. Those samples were immediately examined using SYSMEX SE-9500 automatic analyzer for measuring erythrocytes hematological profile and were stained with Wright staining for morphological examination. These procedures were done before 20 minutes of vein puncture. There were significant decrease of RBC count, HGB, HCT, and MCHC and also significant increase of MCV and RDW between different concentrations of excessive Na2EDTA anticoagulant. MCH did not have significant result. Morphological examination showed significant morphological changes in the form of echinocytes and appearance of ghost cells in the sample treated with excessive Na2EDTA anticoagulant concentration. In conclusion, there are differences in hematological profile and morphology of erythrocytes among blood specimen which are prepared with excessive Na2EDTA anticoagulant in different concentration, except for MCH. Excessive Na2EDTA anticoagulant concentration will affect the blood specimen for peripheral blood examination of erythrocytes by interfering morphology and some of hematological

  1. Effects of elevated atmospheric CO2 concentration and temperature on the soil profile methane distribution and diffusion in rice-wheat rotation system.

    Science.gov (United States)

    Yang, Bo; Chen, Zhaozhi; Zhang, Man; Zhang, Heng; Zhang, Xuhui; Pan, Genxing; Zou, Jianwen; Xiong, Zhengqin

    2015-06-01

    The aim of this experiment was to determine the impacts of climate change on soil profile concentrations and diffusion effluxes of methane in a rice-wheat annual rotation ecosystem in Southeastern China. We initiated a field experiment with four treatments: ambient conditions (CKs), CO2 concentration elevated to ~500 μmol/mol (FACE), temperature elevated by ca. 2°C (T) and combined elevation of CO2 concentration and temperature (FACE+T). A multilevel sampling probe was designed to collect the soil gas at four different depths, namely, 7 cm, 15 cm, 30 cm and 50 cm. Methane concentrations were higher during the rice season and decreased with depth, while lower during the wheat season and increased with depth. Compared to CK, mean methane concentration was increased by 42%, 57% and 71% under the FACE, FACE+T and T treatments, respectively, at the 7 cm depth during the rice season (ptemperature could significantly increase soil profile methane concentrations and their effluxes from a rice-wheat field annual rotation ecosystem (p<0.05). Copyright © 2015. Published by Elsevier B.V.

  2. Comparative QSAR studies on PAMPA/modified PAMPA for high throughput profiling of drug absorption potential with respect to Caco-2 cells and human intestinal absorption

    Science.gov (United States)

    Verma, Rajeshwar P.; Hansch, Corwin; Selassie, Cynthia D.

    2007-01-01

    Despite the dramatic increase in speed of synthesis and biological evaluation of new chemical entities, the number of compounds that survive the rigorous processes associated with drug development is low. Thus, an increased emphasis on thorough ADMET (absorption, distribution, metabolism, excretion and toxicity) studies based on in vitro and in silico approaches allows for early evaluation of new drugs in the development phase. Artificial membrane permeability measurements afford a high throughput, relatively low cost but labor intensive alternative for in vitro determination of drug absorption potential; parallel artificial membrane permeability assays have been extensively utilized to determine drug absorption potentials. The present study provides comparative QSAR analysis on PAMPA/modified PAMPA for high throughput profiling of drugs with respect to Caco-2 cells and human intestinal absorption.

  3. [Profile of prescription and adequacy of treatment with non-steroidal anti-inflammatory drugs in diabetic patients].

    Science.gov (United States)

    Navarro-Martínez, A; Vidal-Martínez, M; García-Rosa, I; Lázaro-Gómez, M J; Brotons-Román, J

    2015-01-01

    The aim of this study was to quantify and describe the prescription profile, as well as to assess the adequacy of treatment with non-steroidal anti-inflammatory drugs (NSAIDs) in the diabetic population of a health district. This is a descriptive, cross-sectional study aimed at a target population of 2,795 diabetic patients. Data were collected from the computerised clinical records of a sample of 380 individuals. The adequacy of treatment was assessed using the recommendations proposed by the Spanish societies of Rheumatology, Cardiology and Gastroenterology. More than one-quarter (28%) of the diabetic patients received treatment with NSAIDs. The most commonly used ones were ibuprofen, naproxen, and dexketoprofen, with a defined daily dose per 1,000 inhabitants per day of 35.3, 17.2, and 13.2, respectively. In patients with a history of chronic kidney disease and cardiovascular high risk, fewer NSAIDs were prescribed, while they were used most frequently in patients with a risk for gastrointestinal adverse events. The prescription was considered adequate in 46.5% of diabetic patients. The main causes of inappropriate use were the inadequate prescription of NSAIDs (25.2%), and the use of any NSAID other than naproxen (20.6%). The most prescribed NSAIDs were those showing a low cardiovascular risk profile. Treatment with NSAIDs was inadequate in more than half of the patients. Risk factors for cardiovascular, and especially gastrointestinal, events must be considered in order to avoid its use when not indicated, as well as the use of any NSAIDs other than naproxen. Copyright © 2015 SECA. Published by Elsevier Espana. All rights reserved.

  4. Superior Effects of Eccentric to Concentric Knee Extensor Resistance Training on Physical Fitness, Insulin Sensitivity and Lipid Profiles of Elderly Men.

    Science.gov (United States)

    Chen, Trevor Chung-Ching; Tseng, Wei-Chin; Huang, Guan-Ling; Chen, Hsin-Lian; Tseng, Kuo-Wei; Nosaka, Kazunori

    2017-01-01

    It has been reported that eccentric training of knee extensors is effective for improving blood insulin sensitivity and lipid profiles to a greater extent than concentric training in young women. However, it is not known whether this is also the case for elderly individuals. Thus, the present study tested the hypothesis that eccentric training of the knee extensors would improve physical function and health parameters (e.g., blood lipid profiles) of older adults better than concentric training. Healthy elderly men (60-76 years) were assigned to either eccentric training or concentric training group ( n = 13/group), and performed 30-60 eccentric or concentric contractions of knee extensors once a week. The intensity was progressively increased over 12 weeks from 10 to 100% of maximal concentric strength for eccentric training and from 50 to 100% for concentric training. Outcome measures were taken before and 4 days after the training period. The results showed that no sings of muscle damage were observed after any sessions. Functional physical fitness (e.g., 30-s chair stand) and maximal concentric contraction strength of the knee extensors increased greater ( P ≤ 0.05) after eccentric training than concentric training. Homeostasis model assessment, oral glucose tolerance test and whole blood glycosylated hemoglobin showed improvement of insulin sensitivity only after eccentric training ( P ≤ 0.05). Greater ( P ≤ 0.05) decreases in fasting triacylglycerols, total, and low-density lipoprotein cholesterols were evident after eccentric training than concentric training, and high-density lipoprotein cholesterols increased only after eccentric training. These results support the hypothesis and suggest that it is better to focus on eccentric contractions in exercise medicine.

  5. Superior Effects of Eccentric to Concentric Knee Extensor Resistance Training on Physical Fitness, Insulin Sensitivity and Lipid Profiles of Elderly Men

    Science.gov (United States)

    Chen, Trevor Chung-Ching; Tseng, Wei-Chin; Huang, Guan-Ling; Chen, Hsin-Lian; Tseng, Kuo-Wei; Nosaka, Kazunori

    2017-01-01

    It has been reported that eccentric training of knee extensors is effective for improving blood insulin sensitivity and lipid profiles to a greater extent than concentric training in young women. However, it is not known whether this is also the case for elderly individuals. Thus, the present study tested the hypothesis that eccentric training of the knee extensors would improve physical function and health parameters (e.g., blood lipid profiles) of older adults better than concentric training. Healthy elderly men (60–76 years) were assigned to either eccentric training or concentric training group (n = 13/group), and performed 30–60 eccentric or concentric contractions of knee extensors once a week. The intensity was progressively increased over 12 weeks from 10 to 100% of maximal concentric strength for eccentric training and from 50 to 100% for concentric training. Outcome measures were taken before and 4 days after the training period. The results showed that no sings of muscle damage were observed after any sessions. Functional physical fitness (e.g., 30-s chair stand) and maximal concentric contraction strength of the knee extensors increased greater (P ≤ 0.05) after eccentric training than concentric training. Homeostasis model assessment, oral glucose tolerance test and whole blood glycosylated hemoglobin showed improvement of insulin sensitivity only after eccentric training (P ≤ 0.05). Greater (P ≤ 0.05) decreases in fasting triacylglycerols, total, and low-density lipoprotein cholesterols were evident after eccentric training than concentric training, and high-density lipoprotein cholesterols increased only after eccentric training. These results support the hypothesis and suggest that it is better to focus on eccentric contractions in exercise medicine. PMID:28443029

  6. Compensating for literature annotation bias when predicting novel drug-disease relationships through Medical Subject Heading Over-representation Profile (MeSHOP) similarity.

    Science.gov (United States)

    Cheung, Warren A; Ouellette, B F Francis; Wasserman, Wyeth W

    2013-01-01

    Using annotations to the articles in MEDLINE®/PubMed®, over six thousand chemical compounds with pharmacological actions have been tracked since 1996. Medical Subject Heading Over-representation Profiles (MeSHOPs) quantitatively leverage the literature associated with biological entities such as diseases or drugs, providing the opportunity to reposition known compounds towards novel disease applications. A MeSHOP is constructed by counting the number of times each medical subject term is assigned to an entity-related research publication in the MEDLINE database and calculating the significance of the count by comparing against the count of the term in a background set of publications. Based on the expectation that drugs suitable for treatment of a disease (or disease symptom) will have similar annotation properties to the disease, we successfully predict drug-disease associations by comparing MeSHOPs of diseases and drugs. The MeSHOP comparison approach delivers an 11% improvement over bibliometric baselines. However, novel drug-disease associations are observed to be biased towards drugs and diseases with more publications. To account for the annotation biases, a correction procedure is introduced and evaluated. By explicitly accounting for the annotation bias, unexpectedly similar drug-disease pairs are highlighted as candidates for drug repositioning research. MeSHOPs are shown to provide a literature-supported perspective for discovery of new links between drugs and diseases based on pre-existing knowledge.

  7. A Ground-Based Direct Detection 1.6μm DIAL for Measurements of Vertical CO2 Concentration Profiles in the Atmosphere

    Science.gov (United States)

    Nagasawa, C.; Abo, M.; Shibata, Y.; Nagai, T.; Sakai, T.; Tsukamoto, M.; Honda, T.

    2011-12-01

    We have developed the ground-based CO2 1.6 μm differential absorption lidar (DIAL) which consists of the optical parametric generator (OPG) transmitter (10mJ/pulse) that excited by the LD pumped Nd:YAG laser with high repetition rate (500Hz) and the receiving optics that included the multi-telescope and the photomultiplier tubes (PMT) with high quantum efficiency (~8%) operating at the photon counting mode. The multi-telescope system is constructed from the combination of multiple telescopes with 20cm to 60cm diameters for the objective altitude range so that the system can reduce the saturation effect of PMTs. Consequentially, the CO2 concentration profiles from ground to an altitude of 10km have been measured with 200m (at the lower altitude range) and 500m (at the upper altitude range) altitude resolutions with better than 1% standard deviation by using this CO2 DIAL. This CO2 DIAL system can be used as the scanning lidar in the atmospheric boundary layer. We also report the 1.6μm DIAL system that can measure the vertical CO2 concentration and temperature profiles in the atmosphere simultaneously. The value of the retrieved CO2 concentration will be improved remarkably by processing the iteration assignment of the CO2 concentration and temperature profiles measured by the CO2 DIAL techniques and the pressure profiles provided from objective analysis data. The 1.6 μm CO2 DIAL system is available to measure the vertical CO2 concentration profiles for nighttime and daytime using the specially designed narrow band interference filter (bandwidth:0.5nm) and the narrow field of view of the receiving telescope. This work was financially supported by the System Development Program for Advanced Measurement and Analysis of the Japan Science and Technology Agency. Reference D. Sakaisawa, C. Nagasawa, T. Nagai, M. Abo, Y. Shibata, H. Nagai, M. Nakazato, and T. Sakai, Development of a 1.6μm differential absorption lidar with a quasi-phase-matching optical parametric

  8. Promising toxicological biomarkers for the diagnosis of liver injury types: Bile acid metabolic profiles and oxidative stress marker as screening tools in drug development.

    Science.gov (United States)

    Masubuchi, Noriko; Nishiya, Takayoshi; Imaoka, Masako; Mizumaki, Kiyoko; Okazaki, Osamu

    2016-08-05

    Promising biomarkers were identified in adult male Crl:CD (SD) rats for the screening of new chemical entities for their potential to cause liver injury. We examined the serum biochemistry, liver histopathology, and bile acid profiles by LC-MS/MS, and the mRNA expression of transporters and CYPs by an RT-PCR after the following treatments to male Crl:CD (SD) rats: (a) bile duct ligation (BDL); (b) a single oral dose of 150 mg/kg α-naphthylisothiocyanate (ANIT); and (c) repeated oral doses of a novel pyrrolidinecarboxylic acid derivative (abbreviated as PCA) at 30, 300, and 1000 mg/kg. The serum total bile acid levels and bilirubin concentrations were found to be elevated in all of the groups. However, the bile acid component profiles of the PCA group differed significantly from BDL and ANIT models: deoxycholic acid, lithocholic acid, and sulfated bile acids were upregulated in a dose-dependent manner only in the PCA group. In addition, the PCA group demonstrated high levels of hepatic heme oxygenase-1 expression, whereas the profiles of the mRNA levels of the hepatic transporters and CYPs of all groups were found to be similar. The histopathological findings, for both the BDL and ANIT groups, were of bile duct hyperplasia, hepatocyte degeneration and necrosis. In contrast, only bile duct hyperplasia and hepatocyte degeneration were observed in the PCA group, even at a lethal dose. These results indicated that PCA induced a cholestatic condition and the increase of oxidative stress markers implies that this will also lead hepatocellular injury. In conclusion, the serum bile acid components and sulfated bile acid levels, and the expression of oxidative stress markers could provide information that aids in the diagnosis of liver injury type and helps to elucidate the mechanisms of hepatotoxicity. These findings can be extrapolated into our clinical investigation. The analysis of these crucial biomarkers is likely to be a useful screening tool in the lead

  9. Genotoxicity assessment of high concentrations of 2,4-D, NAA and Dicamba on date palm callus (Phoenix dactylifera L. using protein profile and RAPD markers

    Directory of Open Access Journals (Sweden)

    Mohammed H. Abass

    2017-06-01

    Full Text Available Genetic stability and uniformity of in vitro-derived date palm plants has a major importance to ascertain true-to-typeness of produced plants. The goal of present study was to evaluate the genetic toxicity of different plant growth regulators on date palm callus at initiation stages using protein patterns and RAPD analysis. Date palm offshoots of Hillawii cultivar were dissected, apical meristems were divided into four segments and cultured on callus induction medium containing the plant growth regulators as 2,4-D at 50 and 100 mg/L; NAA at 30 mg/L and Dicamba at 10 mg/L. The changes occurred in protein profile of callus when treated with high concentration of 2,4-D (100 mg/L, including loss of normal fragments (19 and 66 KDa polypeptides in control, as well as, appearance of new fragments, while at low concentration of 2,4-D (50 mg/L and Dicamba treatment, the protein patterns showed no changes compared to control profile. Similar trends of polymorphisms were obtained with RAPD marker. The high concentration of 2,4-D produced more polymorphic fragments in comparison to control treatment. The DNA profile was identical between 2,4-D at low concentration and control. Dendrograms were generated using similarity indices of protein and RAPD results, and revealed that genetic similarity index was high between 2,4-D treatment at low concentration and control, as separated in one subcluster, followed by Dicamba and NAA, while, the highest genetic distance was obtained between 2,4-D at high concentration and control treatment and separated alone in one cluster.

  10. Variations of protein profiles and calcium and phospholipase A2 concentrations in thawed bovine semen and their relation to acrosome reaction

    Directory of Open Access Journals (Sweden)

    Marques V. Alonso

    2000-01-01

    Full Text Available Just as calcium plays an integral role in acrosome capacitation and reaction, several spermatozoon proteins have been reported as binding to the ovum at fertilization. We examined the relationship between thawed bovine semen protein profiles, seminal plasma calcium ion concentration, spermatozoon phospholipase A2 (PLA2 activity and acrosome reaction. Electrophoretic profile analysis of spermatozoa and bovine seminal plasma proteins (total and membrane revealed qualitative and quantitative differences among bulls. Variations in PLA2 and seminal plasma calcium concentration indicated genetic diversity among individuals. A 15.7-kDa membrane protein was significantly correlated (r = 0.71 with acrosome reaction, which in turn has been associated with in vivo fertility.

  11. Determination of the concentration profile and homogeneity of antioxidants and degradation products in a cross-linked polyethylene type A (PEXa) pipe

    DEFF Research Database (Denmark)

    Denberg, Martin; Mosbæk, Hans; Hassager, Ole

    2009-01-01

    , the concentration profile was measured at four different places on a 100 m PEXa pipe. A two-way ANOVA analysis showed that the composition of Irganox (R) 1076 was homogenous in the radial direction and heterogeneous in the longitudinal direction. Two degradation products of antioxidants were detected, 2,6-di......A solvent extraction technique has been developed to determine the concentration profile of two antioxidants and five degradation products of antioxidants in cross-linked polyethylene (PEX) materials. Irganox (R) 1076 and two degradation products in a PEX pipe type A (PEXa) were detected after...... extraction in chloroform. Fick's second law of diffusion was used to verify that 24 h of extraction at room temperature was sufficient to extract Irganox (R) 1076 and the degradation products from PEX materials with a thickness of 5 pm. With the use of gas chromatography and mass spectrometry...

  12. New procyanidin B3-human salivary protein complexes by mass spectrometry. Effect of salivary protein profile, tannin concentration, and time stability.

    Science.gov (United States)

    Perez-Gregorio, Maria Rosa; Mateus, Nuno; De Freitas, Victor

    2014-10-15

    Several factors could influence the tannin-protein interaction such as the human salivary protein profile, the tannin tested, and the tannin/protein ratio. The goal of this study aims to study the effect of different salivas (A, B, and C) and different tannin concentrations (0.5 and 1 mg/mL) on the interaction process as well as the complex's stability over time. This study is focused on the identification of new procyanidin B3-human salivary protein complexes. Thus, 48 major B3-human salivary protein aggregates were identified regardless of the saliva and tannin concentration tested. A higher number of aggregates was found at lower tannin concentration. Moreover, the number of protein moieties involved in the aggregation process was higher when the tannin concentration was also higher. The selectivity of the different groups of proteins to bind tannin was also confirmed. It was also verified that the B3-human salivary protein complexes formed evolved over time.

  13. Bacteriological Profile and Drug Resistance Patterns of Blood Culture Isolates in a Tertiary Care Nephrourology Teaching Institute

    Directory of Open Access Journals (Sweden)

    Kalpesh Gohel

    2014-01-01

    Full Text Available Blood stream infections can lead to life threatening sepsis and require rapid antimicrobial treatment. The organisms implicated in these infections vary with the geographical alteration. Infections caused by MDR organisms are more likely to increase the risk of death in these patients. The present study was aimed to study the profile of organisms causing bacteremia and understand antibiotic resistance patterns in our hospital. 1440 blood samples collected over a year from clinically suspected cases of bacteremia were studied. The isolates were identified by standard biochemical tests and antimicrobial resistance patterns were determined by CLSI guidelines. Positive blood cultures were obtained in 9.2% of cases of which Gram-positive bacteria accounted for 58.3% of cases with staph aureus predominance; gram negative bacteria accounted for 40.2% with enterobactereciea predominence; and 1.5% were fungal isolates. The most sensitive drugs for Gram-positive isolates were vancomycin, teicoplanin, daptomycin, linezolid, and tigecycline and for Gram-negative were carbapenems, colistin, aminoglycosides, and tigecycline. The prevalence of MRSA and vancomycin resistance was 70.6% and 21.6%, respectively. ESBL prevalence was 39.6%. Overall low positive rates of blood culture were observed.

  14. Profiling of aerosol concentrations, particle size distributions and relative humidity in the atmospheric surface layer over the North Sea

    NARCIS (Netherlands)

    Leeuw, G. de

    1990-01-01

    Results are presented from measurements in the lower 15 m of the marine atmospheric surface layer. The paper is focussed on the comparison of the profile data obtained with the Rotorod and the optical scatterometer. These instruments are based on different physical principles. Results show that

  15. Density profile and cholesterol concentration of serum lipoproteins in experimental animals and human subjects on hypercholesterolaemic diets

    NARCIS (Netherlands)

    Beynen, A.C.; Terpstra, A.H.M.

    1984-01-01

    1. 1. The density profile of Sudan black stained serum lipoproteins was studied in human subjects and various animal species on diets supplemented with cholesterol. 2. 2. In the animals studied (rabbits, calves, mice, chickens, rats and guinea-pigs), the feeding of cholesterol resulted in an

  16. Nonsmoker Exposure to Secondhand Cannabis Smoke. III. Oral Fluid and Blood Drug Concentrations and Corresponding Subjective Effects.

    Science.gov (United States)

    Cone, Edward J; Bigelow, George E; Herrmann, Evan S; Mitchell, John M; LoDico, Charles; Flegel, Ronald; Vandrey, Ryan

    2015-09-01

    The increasing use of highly potent strains of cannabis prompted this new evaluation of human toxicology and subjective effects following passive exposure to cannabis smoke. The study was designed to produce extreme cannabis smoke exposure conditions tolerable to drug-free nonsmokers. Six experienced cannabis users smoked cannabis cigarettes [5.3% Δ(9)-tetrahydrocannabinol (THC) in Session 1 and 11.3% THC in Sessions 2 and 3] in a closed chamber. Six nonsmokers were seated alternately with smokers during exposure sessions of 1 h duration. Sessions 1 and 2 were conducted with no ventilation and ventilation was employed in Session 3. Oral fluid, whole blood and subjective effect measures were obtained before and at multiple time points after each session. Oral fluid was analyzed by ELISA (4 ng/mL cutoff concentration) and by LC-MS-MS (limit of quantitation) for THC (1 ng/mL) and total THCCOOH (0.02 ng/mL). Blood was analyzed by LC-MS-MS (0.5 ng/mL) for THC, 11-OH-THC and free THCCOOH. Positive tests for THC in oral fluid and blood were obtained for nonsmokers up to 3 h following exposure. Ratings of subjective effects correlated with the degree of exposure. Subjective effect measures and amounts of THC absorbed by nonsmokers (relative to smokers) indicated that extreme secondhand cannabis smoke exposure mimicked, though to a lesser extent, active cannabis smoking. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Eimeria oocyst concentrations and species composition in litter from commercial broiler farms during anticoccidial drug or live Eimeria oocyst vaccine control programs

    Science.gov (United States)

    The purpose of this study was to determine if Eimeria oocyst concentrations and species composition in commercial broiler house litter changed during different cycles of anticoccidial drug (ACD) or live Eimeria oocyst vaccine (VAC) control programs, and if there was a correlation between Eimeria ooc...

  18. Nanocomposite formation between alpha-glucosyl stevia and surfactant improves the dissolution profile of poorly water-soluble drug.

    Science.gov (United States)

    Uchiyama, Hiromasa; Tozuka, Yuichi; Nishikawa, Masahiro; Takeuchi, Hirofumi

    2012-05-30

    The formation of a hybrid-nanocomposite using α-glucosyl stevia (Stevia-G) and surfactant was explored to improve the dissolution of flurbiprofen (FP). As reported previously, the dissolution amount of FP was enhanced in the presence of Stevia-G, induced by the formation of an FP and Stevia-G-associated nanostructure. When a small amount of sodium dodecyl sulfate (SDS) was present with Stevia-G, the amount of dissolved FP was extremely enhanced. This dissolution-enhancement effect was also observed with the cationic surfactant of dodecyl trimethyl ammonium bromide, but not with the non-ionic surfactant of n-octyl-β-D-maltopyranoside. To investigate the dissolution-enhancement effect of Stevia-G/SDS mixture, the pyrene I(1)/I(3) ratio was plotted versus the Stevia-G concentration. The pyrene I(1)/I(3) ratio of Stevia-G/SDS mixture had a sigmoidal curve at lower Stevia-G concentrations compared to the Stevia-G solution alone. These results indicate that the Stevia-G/SDS mixture provides a hydrophobic core around pyrene molecules at lower Stevia-G concentrations, leading to nanocomposite formation between Stevia-G and SDS. The nanocomposite of Stevia-G/SDS showed no cytotoxicity to Caco-2 cells at a mixture of 0.1% SDS and 1% Stevia-G solution, whereas 0.1% SDS solution showed high toxicity. These results suggest that the nanocomposite formation of Stevia-G/SDS may be useful way to enhance the dissolution of poorly water-soluble drugs without special treatment. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Tissue Drug Concentrations of Anti-tumor Necrosis Factor Agents Are Associated with the Long-term Outcome of Patients with Crohn's Disease.

    Science.gov (United States)

    Yoshihara, Takeo; Shinzaki, Shinichiro; Kawai, Shoichiro; Fujii, Hironobu; Iwatani, Shuko; Yamaguchi, Toshio; Araki, Manabu; Hiyama, Satoshi; Inoue, Takahiro; Hayashi, Yoshito; Watabe, Kenji; Iijima, Hideki; Takehara, Tetsuo

    2017-12-01

    Many reports indicate that a high-serum trough level of anti-tumor necrosis factor (TNF) agents is required for sustained remission in patients with Crohn's disease The pharmacokinetics of anti-TNF agents in inflamed intestinal tissue, however, is not well investigated. We investigated the association between the tissue concentration of anti-TNF agents and long-term disease outcome. This was a prospective single-center study that enrolled 25 patients with Crohn's disease who were administered infliximab or adalimumab. All participants underwent endoscopy 2 weeks after administration of the anti-TNF agents, and biopsy samples were obtained from both inflamed and noninflamed intestinal tissue. Tissue concentrations of anti-TNF agents were evaluated and the correlation with serum trough levels was compared. The relation between the tissue drug concentration and clinical course over 24 months was also investigated. Concentrations of anti-TNF agents were significantly higher in inflamed tissue than in noninflamed tissue. Patients with high-serum trough concentrations of anti-TNF agents had significantly higher drug levels in the noninflamed tissue than those with low-serum trough concentrations, but no difference in the levels was detected in the inflamed tissue. Patients with high-drug levels in the noninflamed tissue had a significantly higher sustained response rate than patients with low-drug levels. Concentrations of anti-TNF agents in the noninflamed tissue can reflect sustained remission and may be a useful biomarker for monitoring therapeutic intensity in patients with Crohn's disease treated with anti-TNF agents (see Video Abstract, Supplemental Digital Content 1, http://links.lww.com/IBD/B623).

  20. Concentration- and time-dependent genotoxicity profiles of isoprene monoepoxides and diepoxide, and the cross-linking potential of isoprene diepoxide in cells

    Directory of Open Access Journals (Sweden)

    Yan Li

    2014-01-01

    Full Text Available Isoprene, a possible carcinogen, is a petrochemical and a natural product being primarily produced by plants. It is biotransformed to 2-ethenyl-2-methyloxirane (IP-1,2-O and 2-(1-methylethenyloxirane (IP-3,4-O, both of which can be further metabolized to 2-methyl-2,2′-bioxirane (MBO. MBO is mutagenic, but IP-1,2-O and IP-3,4-O are not. While IP-1,2-O has been reported being genotoxic, the genotoxicity of IP-3,4-O and MBO, and the cross-linking potential of MBO have not been examined. In the present study, we used the comet assay to investigate the concentration- and time-dependent genotoxicity profiles of the three metabolites and the cross-linking potential of MBO in human hepatocyte L02 cells. For the incubation time of 1 h, all metabolites showed positive concentration-dependent profiles with a potency rank order of IP-3,4-O > MBO > IP-1,2-O. In human hepatocellular carcinoma (HepG2 and human leukemia (HL60 cells, IP-3,4-O was still more potent in inducing DNA breaks than MBO at high concentrations (>200 μM, although at low concentrations (≤200 μM IP-3,4-O exhibited slightly lower or similar potency to MBO. Interestingly, their time-dependent genotoxicity profiles (0.5–4 h in L02 cells were different from each other: IP-1,2-O and MBO (200 μM exhibited negative and positive profiles, respectively, with IP-3,4-O lying in between, namely, IP-3,4-O-caused DNA breaks did not change over the exposure time. Further experiments demonstrated that hydrolysis of IP-1,2-O contributed to the negative profile and MBO induced cross-links at high concentrations and long incubation times. Collectively, the results suggested that IP-3,4-O might play a significant role in the toxicity of isoprene.

  1. In vitro evaluation of the internalization and toxicological profile of silica nanoparticles and submicroparticles for the design of dermal drug delivery strategies.

    Science.gov (United States)

    Vicente, Sara; Moia, Claudia; Zhu, Huijun; Vigé, Xavier

    2017-12-01

    The use of colloidal silica nanoparticles and sub-microparticles (SiPs) have been considered a very interesting strategy for drug delivery applications. In the present study, we have focused our attention on the suitability of these nanomaterials as potential carriers for dermal drug delivery, thus studying their toxicological profile in vitro, cellular uptake and intracellular localization in both human keratinocytes (K17) and human dermal fibroblasts (HDF) as a function of their particle size (SiPs of 20, 70, 200 and 500 nm). Full characterization of these aspects enabled us to observe a strong cell-type dependency in terms of cytotoxicity and cell internalization, whereas particle size was only relevant for ultra-small SiPs (20 nm), being the most toxic SiPs. For 70, 200 and 500 nm SiPs, the differences in uptake and intracellular trafficking determined the different toxicological profiles in K17 and HDF. In addition, these characteristics can further define different drug delivery strategies. Hence, phagocytosis has been identified as the main internalization mechanism for K17, and caveolae-mediated endocytosis for HDF. This relevant information led us to conclude that fibroblasts would be optimal targets for delivering delicate therapeutic molecules such as proteins or genetic material using SiPs while maintaining a low toxicity profile, whereas keratinocytes could enable accelerated drug release therapies based on SiPs. Copyright © 2017 John Wiley & Sons, Ltd.

  2. Direct observation of solid-phase adsorbate concentration profile in powdered activated carbon particle to elucidate mechanism of high adsorption capacity on super-powdered activated carbon.

    Science.gov (United States)

    Ando, Naoya; Matsui, Yoshihiko; Matsushita, Taku; Ohno, Koichi

    2011-01-01

    Decreasing the particle size of powdered activated carbon (PAC) by pulverization increases its adsorption capacities for natural organic matter (NOM) and polystyrene sulfonate (PSS, which is used as a model adsorbate). A shell adsorption mechanism in which NOM and PSS molecules do not completely penetrate the adsorbent particle and instead preferentially adsorb near the outer surface of the particle has been proposed as an explanation for this adsorption capacity increase. In this report, we present direct evidence to support the shell adsorption mechanism. PAC particles containing adsorbed PSS were sectioned with a focused ion beam, and the solid-phase PSS concentration profiles of the particle cross-sections were directly observed by means of field emission-scanning electron microscopy/energy-dispersive X-ray spectrometry (FE-SEM/EDXS). X-ray emission from sulfur, an index of PSS concentration, was higher in the shell region than in the inner region of the particles. The X-ray emission profile observed by EDXS did not agree completely with the solid-phase PSS concentration profile predicted by shell adsorption model analysis of the PSS isotherm data, but the observed and predicted profiles were not inconsistent when the analytical errors were considered. These EDXS results provide the first direct evidence that PSS is adsorbed mainly in the vicinity of the external surface of the PAC particles, and thus the results support the proposition that the increase in NOM and PSS adsorption capacity with decreasing particle size is due to the increase in external surface area on which the molecules can be adsorbed. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. Soil concentrations and soil-air exchange of organochlorine pesticides along the Aba profile, east of the Tibetan Plateau, western China

    Science.gov (United States)

    Liu, Hongxia; Qi, Shihua; Yang, Dan; Hu, Ying; Li, Feng; Liu, Jia; Xing, Xinli

    2013-12-01

    Mianzhu—Aba profile, east of the Tibetan Plateau, was selected to study the occurrence of organochlorine pesticides (OCPs) along an altitudinal gradient. Dichlorodiphenyltrichloroethanes (DDTs), hexachlorocyclohexanes (HCHs) and Aldrin, Dieldrin and Endrin (Drins) in surface soils were detected in winter (March) and summer (July). Soil concentrations (ng·g-1, dw) in winter and summer ranged as follws: DDTs, 0.37-179.16 and 0.32-42.57; HCHs, 0.14-10.76 and 0.55-32.71; Drins, N.D-3.99 and 0.02-6.93, respectively. Main soil OCPs were p, p'-DDT, p, p'-DDE, β-HCH and Drins, among which Drins were rarely reported in current literature of the Tibetan Plateau. Higher OCP concentrations in the profile were attributed close to the agricultural fields of the Sichuan Basin, current lindane and nondicofol DDTs inputs, and also long-range atmospheric transport from abroad. Soil OCP concentrations underwent obvious seasonal variation, with higher DDTs in winter and higher HCHs and Drins in summer. It may be caused by climatic conditions, summer monsoon type, and physico-chemical properties of such contaminants. Though "rest" phenomenon occurred in some sampling sites, HCHs and Drins showed an increasing trend with increasing altitude, while DDTs showed an evident decrease with increasing altitude. The altitudinal distributions of OCPs were all consistent with previous findings in other mountainous regions. A primary fugacity analysis on OCPs soil-air exchange indicated that the profile may be secondary sources for HCHs and Endrin. As with Aldrin, Dieldrin, and DDTs, the profile may be both secondary sources and sinks.

  4. Non-steroidal anti-inflammatory drug related upper gastrointestinal bleeding: types of drug use and patient profiles in real clinical practice.

    Science.gov (United States)

    Sostres, Carlos; Carrera-Lasfuentes, Patrica; Lanas, Angel

    2017-10-01

    The best available evidence regarding non-steroidal anti-inflammatory drug (NSAID)-related gastrointestinal (GI) bleeding comes from randomized controlled trials including patients who use NSAIDs to manage chronic rheumatic diseases; however, patients with varying background profiles commonly take NSAIDs for many other reasons, often without prescription, and such usage has not been well studied. To define the characteristics of patients hospitalized for upper GI bleeding in clinical practice, we conducted a case-control study among patients with endoscopy-proven major upper GI bleeding due to gastroduodenal peptic lesions and control subjects. We used adjusted logistic regression models to estimate bleeding risks. Data analysis was performed using SPSS 22.0. Our analysis included 3785 cases and 6540 controls, including 1270 cases (33.55%) and 834 controls (12.75%) reporting recent use (NSAIDs including high-dose acetylsalicylic acid (ASA). NSAID use was associated with increased risk of upper GI bleeding, with an adjusted relative risk of 4.86 (95% CI, 4.32-5.46). Acute musculoskeletal pain (36.1%), chronic osteoarthritis (13.5%), and headache (13.6%) were the most common reasons for NSAID use. Among cases, only 17.31% took NSAIDs and 6.38% took high dose ASA due to chronic osteoarthritis. Demographic characteristics significantly differed between subjects with chronic vs. acute musculoskeletal pain. Proton pump inhibitor use was significantly higher in patients who used NSAIDs due to chronic osteoarthritis compared to patients with acute musculoskeletal pain. NSAID (65.15%) or high-dose ASA use (65.83%) preceding upper GI bleeding was most often short-term. In over half of cases (63.62%), the upper GI bleeding event was not preceded by dyspeptic warning symptoms. The majority of patients hospitalized due to NSAID-related upper GI bleeding reported short-term NSAID use for reasons other than chronic rheumatic disease. These findings suggest that current prevention

  5. Distribution of medium-to-coarse glass beads in slurry pipe flow: evaluation of measured concentration profiles

    Czech Academy of Sciences Publication Activity Database

    Matoušek, Václav; Krupička, Jan; Pěník, Vojtěch

    2014-01-01

    Roč. 32, č. 2 (2014), s. 186-196 ISSN 0272-6351. [7th International Conference for Conveying and Handling of Particulate Solids (CHoPS). Friedrichshafen, 10.09.2013-13.09.2012] R&D Projects: GA ČR GA103/09/0383 Institutional support: RVO:67985874 Keywords : concentration distribution * high concentrated slurry * pipeline flow * slurry flow experiment Subject RIV: BK - Fluid Dynamics Impact factor: 0.523, year: 2014

  6. Effect of Theobromine Consumption on Serum Lipoprotein Profiles in Apparently Healthy Humans with Low HDL-Cholesterol Concentrations.

    Science.gov (United States)

    Jacobs, Doris M; Smolders, Lotte; Lin, Yuguang; de Roo, Niels; Trautwein, Elke A; van Duynhoven, John; Mensink, Ronald P; Plat, Jogchum; Mihaleva, Velitchka V

    2017-01-01

    Scope: Theobromine is a major active compound in cocoa with allegedly beneficial effect on high-density-lipoprotein-cholesterol (HDL-CH). We have investigated the effect of theobromine (TB) consumption on the concentrations of triglyceride (TG) and cholesterol (CH) in various lipoprotein (LP) subclasses. Methods: In a randomized, double-blind, placebo-controlled, cross-over study, 44 apparently healthy women and men (age: 60 ± 6 years, BMI: 29 ± 3 kg/m 2 ) with low baseline HDL-CH concentrations consumed a drink supplemented with 500 mg/d theobromine for 4 weeks. TG and CH concentrations in 15 LP subclasses were predicted from diffusion-edited 1 H NMR spectra of fasting serum. Results: The LP phenotype of the subjects was characterized by low CH concentrations in the large HDL particles and high TG concentrations in large VLDL and chylomicron (CM) particles, which clearly differed from a LP phenotype of subjects with normal HDL-CH. TB only reduced CH concentrations in the LDL particles by 3.64 and 6.79%, but had no effect on TG and CH in any of the HDL, VLDL and CM subclasses. Conclusion: TB was not effective on HDL-CH in subjects with a LP phenotype characterized by low HDL-CH and high TG in VLDL.

  7. Effect of Theobromine Consumption on Serum Lipoprotein Profiles in Apparently Healthy Humans with Low HDL-Cholesterol Concentrations

    Directory of Open Access Journals (Sweden)

    Doris M. Jacobs

    2017-08-01

    Full Text Available Scope: Theobromine is a major active compound in cocoa with allegedly beneficial effect on high-density-lipoprotein-cholesterol (HDL-CH. We have investigated the effect of theobromine (TB consumption on the concentrations of triglyceride (TG and cholesterol (CH in various lipoprotein (LP subclasses.Methods: In a randomized, double-blind, placebo-controlled, cross-over study, 44 apparently healthy women and men (age: 60 ± 6 years, BMI: 29 ± 3 kg/m2 with low baseline HDL-CH concentrations consumed a drink supplemented with 500 mg/d theobromine for 4 weeks. TG and CH concentrations in 15 LP subclasses were predicted from diffusion-edited 1H NMR spectra of fasting serum.Results: The LP phenotype of the subjects was characterized by low CH concentrations in the large HDL particles and high TG concentrations in large VLDL and chylomicron (CM particles, which clearly differed from a LP phenotype of subjects with normal HDL-CH. TB only reduced CH concentrations in the LDL particles by 3.64 and 6.79%, but had no effect on TG and CH in any of the HDL, VLDL and CM subclasses.Conclusion: TB was not effective on HDL-CH in subjects with a LP phenotype characterized by low HDL-CH and high TG in VLDL.

  8. Characterisation of selected active agents regarding pKa values, solubility concentrations and pH profiles by SiriusT3.

    Science.gov (United States)

    Schönherr, D; Wollatz, U; Haznar-Garbacz, D; Hanke, U; Box, K J; Taylor, R; Ruiz, R; Beato, S; Becker, D; Weitschies, W

    2015-05-01

    The aim of this work was to determine pKa values and solubility properties of 34active agents using the SiriusT3 apparatus. The selected drug substances belong to the groups of ACE-inhibitors, β-blockers, antidiabetics and lipid lowering substances. Experimentally obtained pKa and intrinsic solubility values were compared to calculated values (program ACD/ChemSketch) and pKa values to published data as well. Solubility-pH profiles were generated to visualise the substance solubility over the gastrointestinal pH range. The relationship between the solubility characteristic of a substance, its bioavailability and categorisation according to the Biopharmaceutics Classification System (BCS) was examined as well. The results showed a good agreement between experimentally obtained, calculated and published pKa values. The measured and calculated intrinsic solubility values indicated several major deviations. All solubility-pH profiles showed the expected shape and appearance for acids, bases or zwitterionic substances. The obtained results for the pKa and solubility measurements of the examined active agents may help to predict their physicochemical behaviour in vivo, and to understand the bioavailability of the substances according to their BCS categorisation. The easy and reproducible determination of pKa and solubility values makes the SiriusT3 apparatus a useful tool in early stages of drug and formulation development. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Modeling Cl{sup -} concentration and δ{sup 37}Cl profiles in pore water across a 250 m-thick indurated argillite at the Tournemire URL (France)

    Energy Technology Data Exchange (ETDEWEB)

    Le Gal La Salle, Corinne; Rebeix, Romain; Lancelot, Joel [Universite de Nimes / Site GIS - 30035 Nimes cedex 01 (France); Aix-Marseille Universite, CEREGE UMR7330, 13545 Aix en Provence (France); Matray, Jean-Michel [IRSN, BP17 - 92262 Fontenay-aux-Roses Cedex (France); Bensenouci, Fethic [IRSN, BP17 - 92262 Fontenay-aux-Roses Cedex (France); IDES, UMR CNRS 8148 Universite Paris-Sud - 91405 Orsay Cedex (France); Michelot, Jean-Luc [IDES, UMR CNRS 8148 Universite Paris-Sud - 91405 Orsay Cedex (France); Dauzeres, Alexandre; Wittebroodt, Charles [IRSN, BP17 - 92262 Fontenay-aux-Roses Cedex (France); Frape, Shaun; ShouakarStash, Orphane [University of Waterloo, 200 University Avenue. West Waterloo, Ontario N2L 3G (Canada)

    2013-07-01

    Dissolved chloride in argillite pore water has been studied as a natural analogue for radionuclides potentially released from radioactive waste disposal. The Tournemire URL intersects impervious and compacted argillite. A previously obtained chloride concentration profile of intact rock is symmetric with a maximum concentration of 0.6±0.1 g/L, compared to 19 g/L for the original connate seawater. Dissolved chloride shows high δ{sup 37}Cl values, ranging between +6 and +80/00 vs. SMOC. The modeled profile considers diffusive exchange between connate seawater and meteoric freshwater. Transport parameters were obtained by radial diffusion experiments. Numerical modeling was performed with the coupled reactive-transport code Hytec. Simulations suggest a diffusive-exchange time of 85±10 Ma for Cl, which correlates with a major erosional period. Simulated δ{sup 37}Cl values between 1.002 and 1.003 agree with observed pore water δ{sup 37}Cl. This study strongly suggests that the dissolved chloride profile in the argillites results from diffusive exchange and indicates that unfractured argillites can provide good confinement. (authors)

  10. Potential of saliva steroid profiling for the detection of endogenous steroid abuse: Reference thresholds for oral fluid steroid concentrations and ratios.

    Science.gov (United States)

    Polet, Michael; De Wilde, Laurie; Van Renterghem, Pieter; Van Gansbeke, Wim; Van Eenoo, Peter

    2018-01-25

    Urine and blood samples are the primary matrices for the detection of exogenous substances in doping control and toxicology. Although these matrices are, in general, very suitable for a wide range of substances, they do show some issues in particular cases. Here, alternative matrices may provide an answer. In this work, a quantitative method for steroid profiling (5 endogenous steroids and their ratios) in oral fluid was developed and validated. In total, 826 saliva samples were analyzed, and inter-individual reference population thresholds for saliva steroid profile parameters were set up. Alterations of this steroid profile after administration of naturally occurring anabolic androgenic steroids (e.g. testosterone (T) or dehydroepiandrosterone (DHEA)) were investigated. In addition, intra-individual short and long-term natural fluctuations were investigated. For longitudinal monitoring in oral fluid, steroid profile ratios (e.g., T/DHEA) were superior to absolute concentrations due to lower susceptibility towards the diurnal pattern. For the detection of a transdermal application of T, the salivary parameter T/DHEA proved to have the highest sensitivity. In contrast with the current screening procedures in urine, there is no need for an additional expensive and time-consuming isotope ratio mass spectrometry confirmation procedure to unequivocally attribute the elevated parameter to an exogenous origin. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. A Critical Review of the Current Evidence for Measuring Drug Concentrations of First-Line Agents Used to Treat Tuberculosis in Children.

    Science.gov (United States)

    Wilby, Kyle John; Shabana, Sara; Ensom, Mary H H; Marra, Fawziah

    2016-01-01

    Tuberculosis is a leading cause of infectious disease-related morbidity and mortality worldwide. Additionally, treatment is complex with most patients requiring combination therapy of first-line agents for multiple months. Children are especially at risk from the medications used to treat tuberculosis and therefore interventions to optimize both efficacy and safety are needed. Protocols exist for therapeutic drug monitoring in tuberculosis patients yet there is a gap in knowledge regarding the extent of any benefits achieved, especially in children. This review aims to summarize and evaluate literature reporting outcomes related to the measurement of drug concentrations of first-line agents used to treat tuberculosis (rifampin, isoniazid, pyrazinamide, ethambutol) in children. Findings showed a lack of strong evidence to support therapeutic drug monitoring in children with tuberculosis. Standard weight-based dosing of first-line agents does not commonly achieve target concentrations yet the effect on clinical outcomes remains unclear. As such, therapeutic drug monitoring should not be recommended currently as a widespread practice for all children with tuberculosis. However, future research should assess any benefit in special populations such as those with relapsing or recurrent disease, or those presenting with adverse drug reactions.

  12. Transcriptomic Profiling of the Saccharomyces cerevisiae Response to Quinine Reveals a Glucose Limitation Response Attributable to Drug-Induced Inhibition of Glucose Uptake▿ †

    Science.gov (United States)

    dos Santos, Sandra C.; Tenreiro, Sandra; Palma, Margarida; Becker, Jorg; Sá-Correia, Isabel

    2009-01-01

    Quinine has been employed in the treatment of malaria for centuries and is still used against severe Plasmodium falciparum malaria. However, its interactions with the parasite remain poorly understood and subject to debate. In this study, we used the Saccharomyces cerevisiae eukaryotic model to better understand quinine's mode of action and the mechanisms underlying the cell response to the drug. We obtained a transcriptomic profile of the yeast's early response to quinine, evidencing a marked activation of genes involved in the low-glucose response (e.g., CAT8, ADR1, MAL33, MTH1, and SNF3). We used a low inhibitory quinine concentration with no detectable effect on plasma membrane function, consistent with the absence of a general nutrient starvation response and suggesting that quinine-induced glucose limitation is a specific response. We have further shown that transport of [14C]glucose is inhibited by quinine, with kinetic data indicating competitive inhibition. Also, tested mutant strains deleted for genes encoding high- and low-affinity hexose transporters (HXT1 to HXT5, HXT8, and HXT10) exhibit resistance phenotypes, correlating with reduced levels of quinine accumulation in the mutants examined. These results suggest that the hexose transporters are facilitators of quinine uptake in S. cerevisiae, possibly through a competitive inhibition mechanism. Interestingly, P. falciparum is highly dependent on glucose uptake, which is mediated by the single-copy transporter PfHT1, a protein with high homology to yeast's hexose transporters. We propose that PfHT1 is an interesting candidate quinine target possibly involved in quinine import in P. falciparum, an uptake mechanism postulated in recent studies to occur through a still-unidentified importer(s). PMID:19805573

  13. Are adverse effects of antiepileptic drugs different in symptomatic partial and idiopathic generalized epilepsies? The Portuguese-Brazilian validation of the Liverpool Adverse Events Profile.

    Science.gov (United States)

    Martins, H H; Alonso, N B; Vidal-Dourado, M; Carbonel, T D; de Araújo Filho, G M; Caboclo, L O; Yacubian, E M; Guilhoto, L M

    2011-11-01

    We report the results of administration of the Portuguese-Brazilian translation of the Liverpool Adverse Events Profile (LAEP) to 100 patients (mean age=34.5, SD=12.12; 56 females), 61 with symptomatic partial epilepsy (SPE) and 39 with idiopathic generalized epilepsy (IGE) (ILAE, 1989) who were on a stable antiepileptic drug (AED) regimen and being treated in a Brazilian tertiary epilepsy center. Carbamazepine was the most commonly used AED (43.0%), followed by valproic acid (32.0%). Two or more AEDs were used by 69.0% of patients. The mean LAEP score (19 questions) was 37.6 (SD=13.35). The most common adverse effects were sleepiness (35.0%), memory problems (35.0%), and difficulty in concentrating (25.0%). Higher LAEP scores were associated with polytherapy with three or more AEDs (P=0.005), female gender (P0.001) and Hospital Anxiety and Depression Scale (Depression: r=0.637, P<0.001; Anxiety: r=0.621, P<0.001) dimensions. LAEP overall scores were similar in people with SPE and IGE and were not helpful in differentiating adverse effects in these two groups. Clinical variables that influenced global LAEP were seizure frequency (P=0.050) and generalized tonic-clonic seizures in the last month (P=0.031) in the IGE group, and polytherapy with three or more AEDs (P=0.003 and P=0.003) in both IGE and SPE groups. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Copper status, serum cholesterol, and milk fatty acid profile in Holstein cows fed varying concentrations of copper.

    Science.gov (United States)

    Engle, T E; Fellner, V; Spears, J W

    2001-10-01

    An experiment was conducted to determine the effects of dietary copper (Cu) on Cu status and lipid metabolism in Holstein cows. Three primiparous and 21 multiparous Holstein cows were utilized in this experiment. Groups of three cows similar in parity, days in milk, and milk yield were assigned randomly to one of the following three treatments: 1) control (no supplemental Cu), 2) 10 mg of Cu/kg of DM from Cu sulfate (CuSO4), and 3) 40 mg of Cu/kg of DM from CuSO4. Liver Cu concentrations were higher in Cu supplemented cows at the end of the 61-d study. Cows receiving 40 mg of Cu/kg of DM had higher liver Cu concentrations than cows receiving 10 mg of Cu. Plasma Cu concentrations were similar across treatments. Total serum cholesterol concentrations were higher in cows receiving supplemental Cu. Cows receiving 40 mg of Cu/kg of DM had higher serum cholesterol concentrations than cows receiving 10 mg of Cu. Dry matter intake, average daily milk production, and milk lipid, protein, and somatic cell numbers were similar across treatments. On d 61, milk fatty acids C18:1 trans and C18-conjugated dienes were lower in cows receiving supplemental Cu relative to the nonsupplemented controls. Cows receiving 40 mg of Cu/kg of DM had higher C12:0 and lower C18:2 and total polyunsaturated fatty acids in milk than cows receiving 10 mg of Cu/kg of DM. These results indicate that Cu supplementation alters lipid metabolism in high producing dairy cows and that Cu supplementation at 40 mg/kg of DM for 61 d can elevate liver Cu concentrations to levels considered to be marginally toxic in dairy cattle.

  15. Polychlorinated biphenyls (PCBs) in industrial and municipal effluents: Concentrations, congener profiles, and partitioning onto particulates and organic carbon

    Energy Technology Data Exchange (ETDEWEB)

    Balasubramani, Aparna, E-mail: aparna.27889@gmail.com; Howell, Nathan L., E-mail: nlhowell@central.uh.edu; Rifai, Hanadi S., E-mail: rifai@uh.edu

    2014-03-01

    Wastewater effluent samples were collected in the summer of 2009 from 16 different locations which included municipal and industrial wastewater treatment plants and petrochemical industrial outfalls in the Houston area. The effluent samples were analyzed for all 209 polychlorinated biphenyls (PCBs) congeners using high resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS) using the USEPA method 1668A. The total PCBs (∑ 209) concentration in the dissolved medium ranged from 1.01 to 8.12 ng/L and ranged from 2.03 to 31.2 ng/L in the suspended medium. Lighter PCB congeners exhibited highest concentrations in the dissolved phase whereas, in the suspended phase, heavier PCBs exhibited the highest concentrations. The PCB homolog concentrations were dominated by monochlorobiphenyls through hexachlorobiphenyls, with dichlorobiphenyls exhibiting the highest concentration amongst them at most of the effluent outfalls, in the suspended phase. Both total suspended solids (TSS) and various organic carbon fractions played an important role in the distribution of the suspended fractions of PCBs in the effluents. The log K{sub oc} values determined in the effluents suggest that effluent PCB loads might have more risk and impact than what standard partitioning models predict. - Highlights: • 209 PCB congeners were measured in 16 different municipal and industrial effluents. • PCB congener differences were elucidated for the various effluent types. • In addition to log K{sub ow}, organic carbon and TSS affect partitioning of PCBs. • High concentrations of homolog 2 maybe due to biotransformation of PCBs.

  16. Modelling of non-steady-state concentration profiles at ISFET-based coulometric sensor-actuator systems

    OpenAIRE

    Olthuis, Wouter; Luo, J.; Luo, J.; van der Schoot, B.H.; van der Schoot, B.H.; Bergveld, Piet; Bos, M.; van der Linden, W.E.

    1990-01-01

    Acid or base concentrations can be determined very rapidly by performing an acid—base titration with coulometrically generated OH− or H+ ions at a noble metal actuator electrode in close proximity to the pH-sensitive gate of an ion-sensitive field effect transistor (ISFET). The ISFET is used as the indicator electrode to detect the equivalence point in the titration curve. Typical values for the time needed to reach the equivalence point are 0.5–10 s for acid or base concentrations ranging fr...

  17. Postmortem Blood Concentrations of R- and S-Enantiomers of Methadone and EDDP in Drug Users: Influence of Co-Medication and P-glycoprotein Genotype

    DEFF Research Database (Denmark)

    Buchard, Anders; Linnet, Kristian; Johansen, Sys Stybe

    2010-01-01

    We investigated toxicological and pharmacogenetic factors that could influence methadone toxicity using postmortem samples. R- and S-methadone were measured in femoral blood from 90 postmortem cases, mainly drug users. The R-enantiomer concentrations significantly exceeded that of the S......-enantiomers (Wilcoxon's test, p methadone only, methadone and strong analgesics, methadone and benzodiazepines, or methadone and other drugs). There was no significant difference in any of the R-methadone/total methadone ratios among......- and S-methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine. No significant association was detected....

  18. Quantitative detection of mass concentration of sand-dust storms via wind-profiling radar and analysis of Z- M relationship

    Science.gov (United States)

    Wang, Minzhong; Ming, Hu; Ruan, Zheng; Gao, Lianhui; Yang, Di

    2018-02-01

    With the aim to achieve quantitative monitoring of sand-dust storms in real time, wind-profiling radar is applied to monitor and study the process of four sand-dust storms in the Tazhong area of the Taklimakan Desert. Through evaluation and analysis of the spatial-temporal distribution of reflectivity factor, it is found that reflectivity factor ranges from 2 to 18 dBz under sand-dust storm weather. Using echo power spectrum of radar vertical beams, sand-dust particle spectrum and sand-dust mass concentration at the altitude of 600 ˜ 1500 m are retrieved. This study shows that sand-dust mass concentration reaches 700 μg/m3 under blowing sand weather, 2000 μg/m3 under sand-dust storm weather, and 400 μg/m3 under floating dust weather. The following equations are established to represent the relationship between the reflectivity factor and sand-dust mass concentration: Z = 20713.5 M 0.995 under floating dust weather, Z = 22988.3 M 1.006 under blowing sand weather, and Z = 24584.2 M 1.013 under sand-dust storm weather. The retrieval results from this paper are almost consistent with previous monitoring results achieved by former researchers; thus, it is implied that wind-profiling radar can be used as a new reference device to quantitatively monitor sand-dust storms.

  19. Development of an achiral supercritical fluid chromatography method with ultraviolet absorbance and mass spectrometric detection for impurity profiling of drug candidates. Part I: Optimization of mobile phase composition.

    Science.gov (United States)

    Lemasson, Elise; Bertin, Sophie; Hennig, Philippe; Boiteux, Hélène; Lesellier, Eric; West, Caroline

    2015-08-21

    Supercritical fluid chromatography (SFC) is a very useful tool in the purpose of impurity profiling of drug candidates, as an adequate selection of stationary phases can provide orthogonal separations so as to maximize the chances to see all impurities. The purpose of the present work is to develop a method for chemical purity assessment. The first part, presented here, focuses on mobile phase selection to ensure adequate elution and detection of drug-like molecules, while the second part focuses on stationary phase selection for optimal separation and orthogonality. The use of additives in the carbon dioxide - solvent mobile phase in SFC is now commonplace, and enables in particular to increase the number of eluted compounds and to improve peak shapes. The objective of this first part was to test different additives (acids, bases, salts and water) for their chromatographic performance assessed in gradient elution with a diode-array detector, but also for the mass responses obtained with a single-quadrupole mass detector, equipped with an electrospray ionization source (Waters ACQUITY QDa). In this project, we used a selection of one hundred and sixty compounds issued from Servier Research Laboratories to screen a set of columns and additives in SFC with a Waters ACQUITY UPC(2) system. The selected columns were all high-performance columns (1.7-1.8μm with totally porous particles or 2.6-2.7μm with superficially porous particles) with a variety of stationary phase chemistries. Initially, eight additives dissolved in the methanol co-solvent were tested on a UPC(2) ACQUITY UPC(2) HSS C18 SB column. A Derringer desirability function was used to classify the additives according to selected criteria: elution capability, peak shapes, UV baseline drift, and UV and mass responses (signal-to-noise ratios). Following these tests, the two best additives (ammonium acetate and ammonium hydroxide) were tested on a larger number of columns (10) where the two additives appeared

  20. Modelling of non-steady-state concentration profiles at ISFET-based coulometric sensor-actuator systems

    NARCIS (Netherlands)

    Olthuis, Wouter; Luo, J.; Luo, J.; van der Schoot, B.H.; van der Schoot, B.H.; Bergveld, Piet; Bos, M.; van der Linden, W.E.

    1990-01-01

    Acid or base concentrations can be determined very rapidly by performing an acid—base titration with coulometrically generated OH− or H+ ions at a noble metal actuator electrode in close proximity to the pH-sensitive gate of an ion-sensitive field effect transistor (ISFET). The ISFET is used as the

  1. Effect of theobromine consumption on serum lipoprotein profiles in apparently healthy humans with low HDL-cholesterol concentrations

    NARCIS (Netherlands)

    Jacobs, Doris M.; Smolders, Lotte; Lin, Yuguang; Roo, de Niels; Trautwein, Elke A.; Duynhoven, van John; Mensink, Ronald P.; Plat, Jogchum; Mihaleva, Velitchka V.

    2017-01-01

    Scope: Theobromine is a major active compound in cocoa with allegedly beneficial effect on high-density-lipoprotein-cholesterol (HDL-CH). We have investigated the effect of theobromine (TB) consumption on the concentrations of triglyceride (TG) and cholesterol (CH) in various lipoprotein (LP)

  2. Effect of different levels of protein concentrates supplementation on the growth performance, plasma amino acids profile andmTORcascade genes expression in early-weaned yak calves.

    Science.gov (United States)

    Peng, Q H; Khan, N A; Xue, B; Yan, T H; Wang, Z S

    2018-02-01

    This study evaluated the effects of different levels of protein concentrate supplementation on the growth performance of yak calves, and correlated the growth rate to changes occurring in the plasma- amino acids, -insulin profile, and signaling activity of mammalian target of rapamycin ( mTOR ) cascade to characterize the mechanism through which the protein synthesis can be improved in early weaned yaks. For this study, 48 early (3 months old) weaned yak calves were selected, and assigned into four dietary treatments according to randomized complete block design. The four blocks were balanced for body weight and sex. The yaks were either grazed on natural pasture (control diet) in a single herd or the grazing yaks was supplemented with one of the three protein rich supplements containing low (17%; LP), medium (19%; MP), or high (21%; HP) levels of crude proteins for a period of 30 days. Results showed that the average daily gain of calves increased (0.14 vs 0.23-0.26 kg; pprotein concentrates supplementation. The concentration of plasma methionine increased (p0.05) when the grazing calves were supplemented with protein concentrates. Compared to control diet, the insulin level of calves increased (psupplementation of protein concentrates. Addition of protein concentrates up-regulated (pprotein sorting 34 homolog, the translational regulators eukaryotic translation initiation factor 4E binding protein 1, and S6 kinase 1 genes in both Longissimus dorsi and semitendinosus. In contrast, the expression of sequestosome 1 was down-regulated in the concentrate supplemented calves. Our results show that protein supplementation improves the growth performance of early weaned yak calves, and that plasma methionine and insulin concentrations were the key mediator for gene expression and protein deposition in the muscles.

  3. Hair cortisol concentrations exhibit a positive association with salivary cortisol profiles and are increased in obese prepubertal girls.

    Science.gov (United States)

    Papafotiou, Chrysanthe; Christaki, Eirini; van den Akker, Erica L T; Wester, Vincent L; Apostolakou, Filia; Papassotiriou, Ioannis; Chrousos, George P; Pervanidou, Panagiota

    2017-03-01

    Cortisol, a key mediator of the stress response, has been associated with obesity and metabolic syndrome manifestations as early as in childhood. Scalp hair cortisol has been proposed as a reliable index of long-term circulating cortisol. We aimed to investigate whether obese prepubertal girls have higher scalp hair cortisol than normal-weight controls and whether hair cortisol levels are correlated with salivary cortisol concentrations in these groups. In this cross-sectional study, 25 obese girls and 25 normal-weighted, age-matched girls were enrolled. Anthropometric evaluation, blood chemistry and salivary cortisol measurements were performed, and body mass index (BMI) and areas under the curve with respect to ground (AUCg) were calculated. Hair cortisol determination was performed with liquid chromatography-tandem mass spectrometry. Both hair cortisol concentrations and salivary cortisol AUCs were higher in the obese than the normal-weight girls (p cortisol and BMI Z-score was found (rho = .327, p = .025), while hair cortisol correlated positively with salivary cortisol AUCg (rho = .3, p = .048). We conclude that obese prepubertal girls have higher hair and salivary cortisol concentrations than their age-matched lean counterparts. Hair cortisol assessment seems to be a sensitive method of evaluating systemic cortisol exposure, which is supported by our finding that hair cortisol is associated with salivary concentrations of the hormone. Lay Summary: Cortisol is the key hormone of the stress response. Childhood obesity has been associated with cortisol production dysregulation. Our findings suggest a positive association between obesity in prepubertal girls and elevated cortisol concentrations, measured in saliva and hair.

  4. Dissolved Oxygen Concentration Profiles in the Hyporheic Zone Through the Use of a High-Density Fiber Optic Measurement Network

    Science.gov (United States)

    Reeder, William Jeffrey; Quick, Annika; Farrell, Tiffany B.; Benner, Shawn G.; Feris, Kevin P.; Tonina, Daniele

    2015-04-01

    The majority of chemical reactions in riverine systems occur within the hyporheic zone (HZ). Hyporheic exchange, flow into and out of the hyporheic zone, represents a primary control over those reactions because the flow rate will determine the residence time and amount of chemical constituents in the HZ. Hyporheic flow can be conceptualized as discreet streamlines that collectively represent a broad distribution of residence times. Within this context, dissolved oxygen (DO) concentration becomes a primary indicator of the redox and biochemical state of the HZ including, for example, the fate of carbon, contaminant behavior, nutrient cycling, stream DO levels and nitrous oxide (N2O) production. River systems have been identified as a significant source of N2O emissions, contributing an estimated 10% of anthropogenically generated N2O. The primary biochemical transformations that lead to N2O production are nitrification (NH4+ to NO3-) and denitrification (NO3- to N2) reactions that are mediated by microbes living in the HZ. Current theory describes a process in which DO enters the stoss side of the HZ and is consumed by respiration and nitrification in the upstream, oxic portion of the streamlines leading to a progressive partitioning of the HZ from oxic to anoxic. This conceptualization, however, has not been well validated in a physical sense, due to inherent difficulties associated with measuring chemical concentrations in the HZ. To test current theory, we measured HZ DO concentrations, in a large-scale flume experiment, almost continuously for five months using a multiplexed optical network and a precision robotic surface probe system. We were able to measure DO at higher spatial and temporal resolution than has been previously demonstrated. These measurements, coupled with detailed numerical modeling of HZ flowlines, allowed us to map HZ DO concentrations spatially and over time. Our findings validate the models that describe the consumption of DO through

  5. Regulatory Perspectives on Strength-Dependent Dissolution Profiles and Biowaiver Approaches for Immediate Release (IR) Oral Tablets in New Drug Applications.

    Science.gov (United States)

    Suarez-Sharp, Sandra; Delvadia, Poonam R; Dorantes, Angelica; Duan, John; Externbrink, Anna; Gao, Zongming; Ghosh, Tapash; Miksinski, Sarah Pope; Seo, Paul

    2016-05-01

    Dissolution profile comparisons are used by the pharmaceutical industry to assess the similarity in the dissolution characteristics of two formulations to decide whether the implemented changes, usually minor/moderate in nature, will have an impact on the in vitro/in vivo performance of the drug product. When similarity testing is applied to support the approval of lower strengths of the same formulation, the traditional approach for dissolution profile comparison is not always applicable for drug products exhibiting strength-dependent dissolution and may lead to incorrect conclusions about product performance. The objective of this article is to describe reasonable biopharmaceutic approaches for developing a biowaiver strategy for low solubility, proportionally similar/non-proportionally similar in composition immediate release drug products that exhibit strength-dependent dissolution profiles. The paths highlighted in the article include (1) approaches to address biowaiver requests, such as the use of multi-unit dissolution testing to account for sink condition differences between the higher and lower strengths; (2) the use of a single- vs. strength-dependent dissolution method; and (3) the use of single- vs. strength-dependent dissolution acceptance criteria. These approaches are cost- and time-effective and can avoid unnecessary bioequivalence studies.

  6. Metabolic profiling of urine and blood plasma in rat models of drug addiction on the basis of morphine, methamphetamine, and cocaine-induced conditioned place preference.

    Science.gov (United States)

    Zaitsu, Kei; Miyawaki, Izuru; Bando, Kiyoko; Horie, Hiroshi; Shima, Noriaki; Katagi, Munehiro; Tatsuno, Michiaki; Bamba, Takeshi; Sato, Takako; Ishii, Akira; Tsuchihashi, Hitoshi; Suzuki, Koichi; Fukusaki, Eiichiro

    2014-02-01

    The metabolic profiles of urine and blood plasma in drug-addicted rat models based on morphine (MOR), methamphetamine (MA), and cocaine (COC)-induced conditioned place preference (CPP) were investigated. Rewarding effects induced by each drug were assessed by use of the CPP model. A mass spectrometry (MS)-based metabolomics approach was applied to urine and plasma of MOR, MA, and COC-addicted rats. In total, 57 metabolites in plasma and 70 metabolites in urine were identified by gas chromatography-MS. The metabolomics approach revealed that amounts of some metabolites, including tricarboxylic acid cycle intermediates, significantly changed in the urine of MOR-addicted rats. This result indicated that disruption of energy metabolism is deeply relevant to MOR addiction. In addition, 3-hydroxybutyric acid, L-tryptophan, cystine, and n-propylamine levels were significantly changed in the plasma of MOR-addicted rats. Lactose, spermidine, and stearic acid levels were significantly changed in the urine of MA-addicted rats. Threonine, cystine, and spermidine levels were significantly increased in the plasma of COC-addicted rats. In conclusion, differences in the metabolic profiles were suggestive of different biological states of MOR, MA, and COC addiction; these may be attributed to the different actions of the drugs on the brain reward circuitry and the resulting adaptation. In addition, the results showed possibility of predict the extent of MOR addiction by metabolic profiling. This is the first study to apply metabolomics to CPP models of drug addiction, and we demonstrated that metabolomics can be a multilateral approach to investigating the mechanism of drug addiction.

  7. A Case Study on Observed and Simulated CO2 Concentration Profiles in Hefei based on Raman Lidar and GEOS-Chem Model

    Directory of Open Access Journals (Sweden)

    Wang Yinan

    2016-01-01

    Full Text Available Observations of atmospheric CO2 concentration profiles provide significative constraints on the global/regional inversions of carbon sources and sinks. Anhui Institute of Optics and Fine Mechanics of Chinese Academy of Sciences developed a Raman Lidar system to detect the vertical distribution of atmospheric CO2. This paper compared the observations with the modeled results from a three-dimensional global chemistry transport model-GEOS-Chem, which showed a good agreement in the trend of change with lidar measurements. The case study indicated a potential for better simulating vertical distribution of atmospheric CO2 by combining with lidar measurements.

  8. Use of the resonant reaction 1H(15N,αγ) for obtaining hydrogen concentration profiles in materials

    International Nuclear Information System (INIS)

    Thomas, J.P.; Pijolat, C.; Fallavier, M.

    1978-01-01

    Experimental results of hydrogen depth profiling in materials, using the resonant nuclear reaction 1 H( 15 N,αγ) (E = 6385 keV) are presented. Such an analysis can be performed with a 2500 kV accelerator. Among the problems inherent to such an ion beam analysis, the influence of the vacuum quality, of the surface state of the targets and of the in-depth hydrogen stability is discussed. Nevertheless it turns out that the analytical performance of the method (depth) resolution of 50 A, analysing depth about one micron and sensitivity down to 50 ppm in silicon) make it potentially the most attractive of the nuclear methods. Various examples are given about the problems encountered and the performance reported [fr

  9. Performance and metabolite profile of dairy cows fed tropical grasses and concentrates containing crude protein with low or high degradability

    Directory of Open Access Journals (Sweden)

    Raphael dos Santos Gomes

    Full Text Available ABSTRACT Ten Holstein-Zebu crossbred cows distributed into two simultaneous Latin squares (5 × 5 as a 2 × 2 factorial arrangement formed by chopped sugarcane or elephant grass silage, both with high or low protein degradability supplements and a corn silage as a control treatment, were compared using orthogonal contrasts. The studied variables were the performance, plasma concentrations of urea-N, glucose, and creatinine, urine-N and milk urea-N, and the nychthemeral variation in NH3-N in the rumen fluid of dairy cows. Nutrient intake, milk production, and milk composition were affected by the treatments. The total mixed ration containing elephant grass silage combined with rumen undegradable protein (RUP provided balanced amounts of carbon and nitrogen in the rumen. This effect may explain the 18% increase in milk yield compared with the other treatments. The diurnal pattern of ruminal NH3-N was interpreted with a sinusoid model. In general, cows fed elephant grass silage exhibited higher concentrations of blood plasma and milk urea-N than animals fed sugarcane. The cows that consumed elephant grass silage with rumen degradable protein concentrate showed a higher milk urea-N compared with animals that consumed elephant grass silage with the RUP concentrate. The use of diets based on corn silage leads to a better use of nitrogen compounds because these diets resulted in lower levels of urea-N in the plasma, urine, and milk at the same level of milk production compared with diets containing elephant grass silage or chopped sugarcane as roughages. In sugarcane-based diets, even greater nitrogen losses in the urine are observed, despite the presence of readily fermentable carbohydrates in the diet.

  10. Gene Expression Profile of Coronary Artery cells Treated with Non-steroidal Anti-inflammatory Drugs Reveals Off-target Effects

    Science.gov (United States)

    Palayoor, Sanjeewani T.; J-Aryankalayil, Molykutty; Makinde, Adeola. Y.; Cerna, David; Falduto, Michael T.; Magnuson, Scott. R.; Coleman, C. Norman

    2012-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) have come under scrutiny because of the gastrointestinal, renal and cardiovascular toxicity associated with prolonged use of these drugs. The purpose of this study was to identify molecular targets for NSAIDs related to cellular toxicity with a view to optimize drug efficacy in clinic. Coronary artery smooth muscle cells (CASMC) and endothelial cells (HCAEC) were treated with low (clinically achievable) and high (typically used in preclinical studies) concentrations of celecoxib (CXB), NS398 (NS) and ibuprofen (IBU) for 24h. NSAIDs-induced gene expression changes were evaluated by microarray analysis and validated by real-time RT-PCR and western blotting. The functional significance of differentially expressed genes was evaluated by Ingenuity Pathway Analysis (IPA). At high concentrations, NSAIDs altered the expression of genes regulating cell proliferation and cell death. NSAIDs also altered genes associated with cardiovascular functions including inflammation, thrombosis, fibrinolysis, coronary artery disease and hypertension. The gene expression was most impacted by IBU, CXB and NS, in that order. This study revealed that NSAIDs altered expression of an array of genes associated with cardiovascular events and emphasizes the potential for fingerprinting drugs in preclinical studies to assess the potential drug toxicity and to optimize the drug efficacy in clinical settings. PMID:22668799

  11. Modelling of the Hypothalamic-Pituitary-Adrenal Axis Perturbations by Externally Induced Cholesterol Pulses of Finite Duration and with Asymmetrically Distributed Concentration Profile

    Science.gov (United States)

    Stanojević, A.; Marković, V. M.; Čupić, Ž.; Vukojević, V.; Kolar-Anić, L.

    2017-12-01

    A model was developed that can be used to study the effect of gradual cholesterol intake by food on the HPA axis dynamics. Namely, well defined oscillatory dynamics of vital neuroendocrine hypothalamic-pituitary-adrenal (HPA) axis has proven to be necessary for maintaining regular basal physiology and formulating appropriate stress response to various types of perturbations. Cholesterol, as a precursor of all steroid HPA axis hormones, can alter the dynamics of HPA axis. To analyse its particular influence on the HPA axis dynamics we used stoichiometric model of HPA axis activity, and simulate cholesterol perturbations in the form of finite duration pulses, with asymmetrically distributed concentration profile. Our numerical simulations showed that there is a complex, nonlinear dependence between the HPA axis responsiveness and different forms of applied cholesterol concentration pulses, indicating the significance of kinetic modelling, and dynamical systems theory for the understanding of large-scale self-regulatory, and homeostatic processes within this neuroendocrine system.

  12. Response of Plasmodium falciparum to cotrimoxazole therapy: relationship with plasma drug concentrations and dihydrofolate reductase and dihydropteroate synthase genotypes

    DEFF Research Database (Denmark)

    Khalil, Insaf F; Rønn, Anita M; Alifrangis, Michael

    2005-01-01

    treatment and at days 3, 7, and 14 or upon recrudescence to ascertain drug absorption. Forty patients (89%) had an adequate clinical response, one patient (2%) had an early treatment failure response, while four patients (8%) showed late treatment failure responses. Genotyping of merozoite surface protein 1......, MSP-1, MSP-2, and glutamate-rich protein before treatment and upon recrudescence showed that all recurring parasites were recrudescences. The plasma levels of TRM, AcSMX, and SMX indicated adequate drug absorption in all patients. This suggests parasite resistance as a cause of treatment failure...

  13. Anticonvulsant profile and teratogenicity of 3,3-dimethylbutanoylurea: a potential for a second generation drug to valproic acid.

    Science.gov (United States)

    Shimshoni, Jakob Avi; Yagen, Boris; Pessah, Neta; Wlodarczyk, Bogdan; Finnell, Richard H; Bialer, Meir

    2008-07-01

    The purpose of this study was to evaluate the anticonvulsant activity and teratogenic potential of branched aliphatic acylureas represented by isovaleroylurea (IVU), pivaloylurea (PVU) and 3,3-dimethylbutanoylurea (DBU), as potential second-generation drugs to valproic acid (VPA). The anticonvulsant activity of IVU, PVU, and DBU was determined in mice and rats utilizing the maximal electroshock seizure (MES) and the pentylenetetrazole (scMet) tests. The ability of DBU to block electrical-, or chemical-induced seizures was further examined in three acute seizure models: the psychomotor 6 Hz model, the bicuculline and picrotoxin models and one model of chronic epilepsy (i.e., the hippocampal kindled rat model). The induction of neural tube defects (NTDs) by IVU, PVU, and DBU was evaluated after i.p. administration at day 8.5 of gestation to a mouse strain highly susceptible to VPA-induced teratogenicity. The pharmacokinetics of DBU was studied following i.v. administration to rats. DBU emerged as the most potent compound having an MES-ED(50)of 186 mg/kg (mice) and 64 mg/kg (rats) and an scMet-ED(50)of 66 mg/kg (mice) and 26 mg/kg (rats). DBU underwent further evaluation in the hippocampal kindled rat (ED(50)= 35 mg/kg), the psychomotor 6 Hz mouse model (ED(50)= 80 mg/kg at 32 mA and ED(50)= 133 mg/kg at 44 mA), the bicuculline- and picrotoxin-induced seizure mouse model (ED(50)= 205 mg/kg and 167 mg/kg, respectively). In contrast to VPA, DBU, IVU, and PVU did not induce a significant increase in NTDs as compared to control. DBU was eliminated by metabolism with a half-life of 4.5 h. DBU's broad spectrum and potent anticonvulsant activity, along with its high safety margin and favorable pharmacokinetic profile, make it an attractive candidate to become a new, potent, and safe AED.

  14. Profiling patterns of fecal 20-oxopregnane concentrations during ovarian cycles in free-ranging southern white rhinoceros (Ceratotherium simum simum).

    Science.gov (United States)

    van der Goot, Annemieke Catharina; Martin, Graeme Bruce; Millar, Robert Peter; Paris, Monique Christina Johanna; Ganswindt, Andre

    2015-10-01

    Unlike their wild counterparts, many white rhinoceros females in captivity fail to reproduce successfully such that current captive populations are not self-sustaining. The causes of the problem are poorly understood. Variation in cycle length and long periods of acyclicity are characteristics of the majority of these non-reproducing females in captivity but it is unknown whether these characteristics are a feature of reproductively successful free-ranging females. This study therefore aimed to monitor cyclic activity in a wild population of southern white rhinoceros at Lapalala Wilderness, South Africa, by measuring the concentrations of immunoreactive fecal progestagen metabolites (fPM). Five adult females were tracked twice per week for 20 months and if located a fresh fecal sample was collected. Reproductive events and group structural dynamics were also recorded and subsequently correlated with the fPM data. The baseline concentration of fPM was 0.69±0.20μg/g DW while concentrations during pregnancy were 30-400-fold higher. The females exhibited estrous cycle lengths of 30.6±7.7 days and, based on fPM data, gestation length in one female was 502±3 days. Year-round monitoring showed no clear evidence of seasonality in ovarian activity. During cyclic luteal activity females were often seen in the presence of a dominant bull. One female stopped cycling after removal of the local dominant bull and luteal activity only returned after a new bull was introduced. This suggests that white rhinoceros females in the wild might need external stimuli from a male to ovulate. These findings indicate that the irregular cyclicity reported for white rhinoceros housed in zoos and animal parks may result from conditions in captivity and account for reduced fertility. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Drug resistance in colorectal cancer cell lines is partially associated with aneuploidy status in light of profiling gene expression

    DEFF Research Database (Denmark)

    Guo, Jiao; Xu, Shaohang; Huang, Xuanlin

    2016-01-01

    A priority in solving the problem of drug resistance is to understand the molecular mechanism of how a drug induces the resistance response within cells. Because many cancer cells exhibit chromosome aneuploidy, we explored whether changes of aneuploidy status result in drug resistance. Two typical...... colorectal cancer cells, HCT116 and LoVo, were cultured with the chemotherapeutic drugs irinotecan (SN38) or oxaliplatin (QxPt), and the non- and drug-resistant cell lines were selected. Whole exome sequencing (WES) was employed to evaluate the aneuploidy status of these cells, and RNAseq and LC-MS/MS were...... the aneuploidy status in cancer cells, which was partially associated with the acquired drug resistance....

  16. Depth profiles of temperature, specific conductance and oxygen concentration in Lake Powell, Arizona-Utah, 1992-95

    Science.gov (United States)

    Marzolf, G. Richard; Hart, Robert J.; Stephens, Doyle W.

    1998-01-01

    The depth distribution of temperature in lakes and reservoirs establishes vertical-density gradients that regulate the distribution of a wide array of chemical and biological features. In Lake Powell, the depth at which inflowing river water enters the reservoir is controlled by the water temperature of the river compared to the vertical-thermal structure of the reservoir in late spring and early summer. The measurements reported here document the longitudinal and vertical pattern of temperature, specific conductance, and oxygen concentration on several dates in 1992, 1994, and 1995.

  17. Concentration profiles in the wake of a sphere buried in a granular bed through which fluid flows

    International Nuclear Information System (INIS)

    Guedes de Carvalho, J.R.F.; Delgado, J.M.P.Q.; Alves, M.A.

    2005-01-01

    The concentration distribution in the wake of a soluble sphere immersed in a granular bed of inerts has been obtained numerically, for transport by both advection and diffusion/dispersion. Fluid flow in the granular bed around the sphere was assumed to follow Darcy's law and, at each point, dispersion of solute was considered in both the cross-stream and stream-wise directions. The elliptic PDE equation, resulting from a differential material balance on the solute, has been solved numerically over a wide range of values of the relevant parameters. (authors)

  18. Concentration profiles in the wake of a sphere buried in a granular bed through which fluid flows

    Energy Technology Data Exchange (ETDEWEB)

    Guedes de Carvalho, J.R.F.; Delgado, J.M.P.Q.; Alves, M.A. [Porto Univ., Dpet. de Engenharia Quimica, Faculdade de Engenharia (Portugal)

    2005-07-01

    The concentration distribution in the wake of a soluble sphere immersed in a granular bed of inerts has been obtained numerically, for transport by both advection and diffusion/dispersion. Fluid flow in the granular bed around the sphere was assumed to follow Darcy's law and, at each point, dispersion of solute was considered in both the cross-stream and stream-wise directions. The elliptic PDE equation, resulting from a differential material balance on the solute, has been solved numerically over a wide range of values of the relevant parameters. (authors)

  19. Spectra and concentration profiles throughout the reaction of curing epoxy resins from near-infrared spectroscopy and multivariate curve resolution methods.

    Science.gov (United States)

    Larrechi, M S; Rius, F X

    2004-01-01

    When applied to near-infrared (NIR) data, multivariate curve resolution methods, in particular alternating least squares (ALS), make it possible to calculate the concentration profiles and the spectra of all species involved in the reaction of curing epoxy resins. In this paper, the model reaction between phenyl glicidyl ether and aniline (2:1) was studied at 95 degrees C. A NIR spectrum was recorded every five minutes throughout the eight-hour reaction process. The data display rank deficiency. This problem was overcome by supplying additional information to the system in the form of known spectra of some reactants. The recovered spectra and concentration profiles satisfactorily reproduced the experimental data. In this way, 99.99% of the variance associated with the experimental matrix was reproduced. A value of 0.87% was obtained for lack of fit while the similarity coefficient r between the spectra recovered and the spectra corresponding to the three pure species involved in the reaction were PGE (r = 0.994), aniline (r = 0.994), and tertiary amine (r = 0.999). The maximum and minimum limits associated with the ALS solutions were calculated, which made it possible to limit to a considerable extent the ambiguity that is characteristic of these curve resolution methods.

  20. Physically based method for measuring suspended-sediment concentration and grain size using multi-frequency arrays of acoustic-doppler profilers

    Science.gov (United States)

    Topping, David J.; Wright, Scott A.; Griffiths, Ronald; Dean, David

    2014-01-01

    As the result of a 12-year program of sediment-transport research and field testing on the Colorado River (6 stations in UT and AZ), Yampa River (2 stations in CO), Little Snake River (1 station in CO), Green River (1 station in CO and 2 stations in UT), and Rio Grande (2 stations in TX), we have developed a physically based method for measuring suspended-sediment concentration and grain size at 15-minute intervals using multifrequency arrays of acoustic-Doppler profilers. This multi-frequency method is able to achieve much higher accuracies than single-frequency acoustic methods because it allows removal of the influence of changes in grain size on acoustic backscatter. The method proceeds as follows. (1) Acoustic attenuation at each frequency is related to the concentration of silt and clay with a known grain-size distribution in a river cross section using physical samples and theory. (2) The combination of acoustic backscatter and attenuation at each frequency is uniquely related to the concentration of sand (with a known reference grain-size distribution) and the concentration of silt and clay (with a known reference grain-size distribution) in a river cross section using physical samples and theory. (3) Comparison of the suspended-sand concentrations measured at each frequency using this approach then allows theory-based calculation of the median grain size of the suspended sand and final correction of the suspended-sand concentration to compensate for the influence of changing grain size on backscatter. Although this method of measuring suspended-sediment concentration is somewhat less accurate than using conventional samplers in either the EDI or EWI methods, it is much more accurate than estimating suspended-sediment concentrations using calibrated pump measurements or single-frequency acoustics. Though the EDI and EWI methods provide the most accurate measurements of suspended-sediment concentration, these measurements are labor-intensive, expensive, and

  1. Organophosphate flame retardants (OPFRs) in indoor and outdoor air in the Rhine/Main area, Germany: comparison of concentrations and distribution profiles in different microenvironments.

    Science.gov (United States)

    Zhou, Lingli; Hiltscher, Marco; Gruber, Daniel; Püttmann, Wilhelm

    2017-04-01

    The concentrations of 9 organophosphate flame retardants (OPFRs) were determined in 56 indoor and 9 outdoor air samples in the Rhine/Main area in Germany. The indoor samples were collected from seven different indoor microenvironments including private cars, private homes, floor/carpet stores, building material markets, schools, offices, and day care centers, while outdoor samples were simultaneously collected close to the indoor sampling locations. The total OPFR concentrations (∑OPFRs) in indoor air ranged from 3.30 to 751.0 ng/m 3 with a median of 40.23 ng/m 3 , which was approximately eight times higher than those in outdoor air (median 5.38 ng/m 3 ), indicating that sources of OPFRs predominate in the indoor environment. Tris(2-chloroisopropyl)phosphate (TCPP), tris(isobutyl)phosphate (TiBP), and tributyl phosphate (TnBP) were the dominating compounds both in indoor and outdoor air. The median concentration of ∑OPFRs in private cars (180.3 ng/m 3 ) was significantly higher than that in private homes (12.51 ng/m 3 ), schools (36.23 ng/m 3 ), day care centers (31.80 ng/m 3 ), and building material markets (31.17 ng/m 3 ) (p TDCPP, and TCPP, whose concentrations were closely associated with the distribution profiles and pollution characteristics of materials predominating in different indoor microenvironments.

  2. The relationship between chemical concentration and odor activity value explains the inconsistency in making a comprehensive surrogate scent training tool representative of illicit drugs.

    Science.gov (United States)

    Rice, Somchai; Koziel, Jacek A

    2015-12-01

    This report highlights the importance of an individual chemical's odor impact in the olfactory identification of marijuana, cocaine, and heroin. There are small amounts of highly odorous compounds present in headspace of these drugs, with very low odor detection thresholds, that are more likely responsible for contributing to the overall odor of these drugs. Previous reports of the most abundant compounds in headspace can mislead researchers when dealing with whole odor of these drugs. Surrogate scent formulations, therefore, must match the odor impact of key compounds and not just the chemical abundance of compounds. The objective of this study was to compare odorous volatile organic compounds (VOCs) emitted from illicit drug samples of marijuana, cocaine, and heroin to surrogate smell formulations using simultaneous sensory (via human olfaction) and chemical analyses. Use of solid phase microextraction (SPME) allowed VOCs in drug headspace to be extracted and pre-concentrated on site, and analyzed by multidimensional gas chromatography-mass spectrometry-olfactometry (MDGC-MS-O). Use of MDGC-MS-O allowed for further separation of odorous compounds and simultaneous detection by the human nose of the separate odor parts that make up the total aroma of these drugs. The compounds most abundant in headspace were not the most odor impactful when ranked by odor activity values (OAVs) (defined as ratio of concentration to odor detection threshold, ODT). There were no apparent correlations between concentrations and OAVs. A 1g marijuana surrogate lacked in odor active acids, aldehydes, ethers, hydrocarbons, N-containing, and S-containing VOCs and was overabundant in odor active alcohols and aromatics compared with real marijuana. A 1g cocaine surrogate was overabundant in odor active alcohols, aldehydes, aromatics, esters, ethers, halogenates, hydrocarbons, ketones and N-containing compounds compared with real. A 1g heroin surrogate should contain less odor active acids

  3. Effect of different levels of protein concentrates supplementation on the growth performance, plasma amino acids profile and cascade genes expression in early-weaned yak calves

    Directory of Open Access Journals (Sweden)

    Q. H. Peng

    2018-02-01

    Full Text Available Objective This study evaluated the effects of different levels of protein concentrate supplementation on the growth performance of yak calves, and correlated the growth rate to changes occurring in the plasma- amino acids, -insulin profile, and signaling activity of mammalian target of rapamycin (mTOR cascade to characterize the mechanism through which the protein synthesis can be improved in early weaned yaks. Methods For this study, 48 early (3 months old weaned yak calves were selected, and assigned into four dietary treatments according to randomized complete block design. The four blocks were balanced for body weight and sex. The yaks were either grazed on natural pasture (control diet in a single herd or the grazing yaks was supplemented with one of the three protein rich supplements containing low (17%; LP, medium (19%; MP, or high (21%; HP levels of crude proteins for a period of 30 days. Results Results showed that the average daily gain of calves increased (0.14 vs 0.23–0.26 kg; p0.05 when the grazing calves were supplemented with protein concentrates. Compared to control diet, the insulin level of calves increased (p<0.05; 1.86 vs 2.16–2.54 μIU/mL with supplementation of protein concentrates. Addition of protein concentrates up-regulated (p<0.05 expression of mTOR-raptor, mammalian vacuolar protein sorting 34 homolog, the translational regulators eukaryotic translation initiation factor 4E binding protein 1, and S6 kinase 1 genes in both Longissimus dorsi and semitendinosus. In contrast, the expression of sequestosome 1 was down-regulated in the concentrate supplemented calves. Conclusion Our results show that protein supplementation improves the growth performance of early weaned yak calves, and that plasma methionine and insulin concentrations were the key mediator for gene expression and protein deposition in the muscles.

  4. Pore-water sulfate concentration profiles of sediment cores from Krishna-Godavari and Goa basins, India

    Digital Repository Service at National Institute of Oceanography (India)

    Mazumdar, A.; Paropkari, A.L.; Borole, D.V.; Rao, B.R.; Khadge, N.H.; Karisiddaiah, S.M.; Kocherla, M.; Joao, H.M.

    .002-0.006 g cm -2 y -1 respectively. This would mean an organic carbon burial flux of 1.61x10 -4 to 3.33x10 -4 gC cm -2 y -1 for K-G sediments and 1.08 x10 -5 to 4.19x10 -5 gC cm -2 y -1 for Goa sediments. The range of organic carbon burial flux... 302520151050 J= 3.6-3.7 Depth (cm) J = 9.2-9.5 0 100 200 300 GH4/GC-30 y = -0.0736x + 23.958 R 2 = 0.9479 J = 10.7-10.8 302520151050 y = -0.0708x + 22.422 R 2 = 0.9667 100 200 300 400 GH4/GC-48 302520151050 0 J = 10.5-10.8 Sulfate Concentration (mM) y = -0...

  5. Doxorubicin-Loaded QuadraSphere Microspheres: Plasma Pharmacokinetics and Intratumoral Drug Concentration in an Animal Model of Liver Cancer

    OpenAIRE

    Lee, Kwang-Hun; Liapi, Eleni A.; Cornell, Curt; Reb, Philippe; Buijs, Manon; Vossen, Josephina A.; Ventura, Veronica Prieto; Geschwind, Jean-Francois H.

    2010-01-01

    The purpose of this study was to evaluate, in vitro and in vivo, doxorubicin-loaded poly (vinyl alcohol-sodium acrylate) copolymer microspheres [QuadraSphere microspheres (QSMs)] for transcatheter arterial delivery in an animal model of liver cancer. Doxorubicin loading efficiency and release profile were first tested in vitro. In vivo, 15 rabbits, implanted with a Vx-2 tumor in the liver, were divided into three groups of five rabbits each, based on the time of euthanasia. Twenty-five millig...

  6. Analytical Profiling of Airplane Wastewater - a New Matrix for Mapping Worldwide Patterns of Drug Use and Abuse

    DEFF Research Database (Denmark)

    Mardal, Marie; Aarestrup, Frank Møller; Rasmussen, Brian Schou

    2017-01-01

    There is limited knowledge on the global prescription and consumption patterns of therapeutic (TD) and illicit drugs (ID). Pooled urine analysis and wastewater-based epidemiology (WBE) has been used for local-based drug screening. It is, however, difficult to study the global epidemiology due...

  7. Ketamine coadministration attenuates morphine tolerance and leads to increased brain concentrations of both drugs in the rat

    Science.gov (United States)

    Lilius, T O; Jokinen, V; Neuvonen, M S; Niemi, M; Kalso, E A; Rauhala, P V

    2015-01-01

    Background and Purpose The effects of ketamine in attenuating morphine tolerance have been suggested to result from a pharmacodynamic interaction. We studied whether ketamine might increase brain morphine concentrations in acute coadministration, in morphine tolerance and morphine withdrawal. Experimental Approach Morphine minipumps (6 mg·day–1) induced tolerance during 5 days in Sprague–Dawley rats, after which s.c. ketamine (10 mg·kg–1) was administered. Tail flick, hot plate and rotarod tests were used for behavioural testing. Serum levels and whole tissue brain and liver concentrations of morphine, morphine-3-glucuronide, ketamine and norketamine were measured using HPLC-tandem mass spectrometry. Key Results In morphine-naïve rats, ketamine caused no antinociception whereas in morphine-tolerant rats there was significant antinociception (57% maximum possible effect in the tail flick test 90 min after administration) lasting up to 150 min. In the brain of morphine-tolerant ketamine-treated rats, the morphine, ketamine and norketamine concentrations were 2.1-, 1.4- and 3.4-fold, respectively, compared with the rats treated with morphine or ketamine only. In the liver of morphine-tolerant ketamine-treated rats, ketamine concentration was sixfold compared with morphine-naïve rats. After a 2 day morphine withdrawal period, smaller but parallel concentration changes were observed. In acute coadministration, ketamine increased the brain morphine concentration by 20%, but no increase in ketamine concentrations or increased antinociception was observed. Conclusions and Implications The ability of ketamine to induce antinociception in rats made tolerant to morphine may also be due to increased brain concentrations of morphine, ketamine and norketamine. The relevance of these findings needs to be assessed in humans. PMID:25297798

  8. Mycobacterial interspersed repetitive unit typing and mutational profile for multidrug-resistant and extensively drug-resistant tuberculosis surveillance in Portugal: a 3-year period overview.

    Science.gov (United States)

    Silva, Carla; Perdigão, João; Jordão, Luísa; Portugal, Isabel

    2014-12-01

    Multidrug tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) cases constitute a serious health problem in Portugal, of which the majority of isolates belong to the Lisboa family and the Q1 cluster, highly related to the Lisboa family. Here we sought to investigate the molecular basis of resistant TB as well as to determine the prevalence of specific drug resistance mutations and their association with MDR-TB and/or XDR-TB. In total, 74 Mycobacterium tuberculosis clinical isolates collected in Lisbon Health Region were genotyped by 24-loci mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR), and the mutational profile associated with first- and second-line drug resistance was studied. Seven new mutations were found, whilst the remaining 28 mutations had been previously associated with drug resistance. None of the mutations was specifically associated with MDR-TB. The mutational patterns observed among isolates belonging to Lisboa3 and Q1 clusters were also observed in isolates with unique MIRU-VNTR patterns but closely related to these strains. Such data suggest that the genotyping technique employed discriminates isolates with the same mutational profile. To establish the most adequate genotyping technique, the discriminatory power of three different MIRU-VNTR sets was analysed. The 15-loci MIRU-VNTR set showed adequate discriminatory power, comparable with the 24-loci set, allowing clustering of 60% and 86% of the MDR-TB and XDR-TB isolates, respectively, the majority of which belonged to the Lisboa3 and Q1 clusters. From an epidemiological standpoint, this study suggests combined mutational and genotyping analysis as a valuable tool for drug resistance surveillance. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  9. Profile of female patients seeking in-patient treatment for prescription opioid abuse from a tertiary care drug dependence treatment centre from India

    Directory of Open Access Journals (Sweden)

    Prabhoo Dayal

    2016-01-01

    Full Text Available Background & objectives: There has been a limited focus on prescription drug abuse among women in the country. Choice of psychoactive substance, reasons for initiation and co-occurring disorders have been found to be different among men and women. The current study was aimed at studying the profile of female patients seeking in-patient treatment for prescription drug use over a period of five years at a tertiary care drug dependence treatment centre in India. Methods: Case records of all female patients admitted with substance use disorder at a national level drug dependence treatment centre in north India across five years (between January 2008 and December 2012 were reviewed retrospectively to study their socio-demographic and clinical profile. The information was gathered using a semi-structured proforma and detailed case records. Abstinence, relapse and retention rates were calculated. Results: Over the five years, 31 female patients were admitted with prescription drug abuse. Of them, 12 (39% used prescription opioids and 11 (36% used prescription opioid along with benzodiazepines. Commonest prescription opioid was pentazocine used by 87 per cent of the women. Twenty two (71% women were introduced to opioid by medical practitioners and commonest reason for introduction was pain (among 48%. Common co-occurring psychiatric diagnoses were depressive disorder (26%, cluster B traits/disorder (19% and somatoform disorder (13%. Eight women did not complete treatment and left against medical advice. Thirteen women were advised maintenance treatment, and 70 per cent of them were retained for at least six months. Interpretation & conclusions: Our findings revealed a link between mental illness, pain and non-medical use of prescription opioids among women. Majority of these women received opioids as a legitimate prescription form physician. Therefore, these legitimate prescribers should be trained for pain management to facilitate proper treatment of

  10. Comprehensive data-driven analysis of the impact of chemoinformatic structure on the genome-wide biological response profiles of cancer cells to 1159 drugs.

    Science.gov (United States)

    Khan, Suleiman A; Faisal, Ali; Mpindi, John Patrick; Parkkinen, Juuso A; Kalliokoski, Tuomo; Poso, Antti; Kallioniemi, Olli P; Wennerberg, Krister; Kaski, Samuel

    2012-05-30

    Detailed and systematic understanding of the biological effects of millions of available compounds on living cells is a significant challenge. As most compounds impact multiple targets and pathways, traditional methods for analyzing structure-function relationships are not comprehensive enough. Therefore more advanced integrative models are needed for predicting biological effects elicited by specific chemical features. As a step towards creating such computational links we developed a data-driven chemical systems biology approach to comprehensively study the relationship of 76 structural 3D-descriptors (VolSurf, chemical space) of 1159 drugs with the microarray gene expression responses (biological space) they elicited in three cancer cell lines. The analysis covering 11350 genes was based on data from the Connectivity Map. We decomposed the biological response profiles into components, each linked to a characteristic chemical descriptor profile. Integrated analysis of both the chemical and biological space was more informative than either dataset alone in predicting drug similarity as measured by shared protein targets. We identified ten major components that link distinct VolSurf chemical features across multiple compounds to specific cellular responses. For example, component 2 (hydrophobic properties) strongly linked to DNA damage response, while component 3 (hydrogen bonding) was associated with metabolic stress. Individual structural and biological features were often linked to one cell line only, such as leukemia cells (HL-60) specifically responding to cardiac glycosides. In summary, our approach identified several novel links between specific chemical structure properties and distinct biological responses in cells incubated with these drugs. Importantly, the analysis focused on chemical-biological properties that emerge across multiple drugs. The decoding of such systematic relationships is necessary to build better models of drug effects, including

  11. Profile of female patients seeking in-patient treatment for prescription opioid abuse from a tertiary care drug dependence treatment centre from India.

    Science.gov (United States)

    Dayal, Prabhoo; Balhara, Yatan Pal Singh

    2016-01-01

    There has been a limited focus on prescription drug abuse among women in the country. Choice of psychoactive substance, reasons for initiation and co-occurring disorders have been found to be different among men and women. The current study was aimed at studying the profile of female patients seeking in-patient treatment for prescription drug use over a period of five years at a tertiary care drug dependence treatment centre in India. Case records of all female patients admitted with substance use disorder at a national level drug dependence treatment centre in north India across five years (between January 2008 and December 2012) were reviewed retrospectively to study their socio-demographic and clinical profile. The information was gathered using a semi-structured proforma and detailed case records. Abstinence, relapse and retention rates were calculated. Over the five years, 31 female patients were admitted with prescription drug abuse. Of them, 12 (39%) used prescription opioids and 11 (36%) used prescription opioid along with benzodiazepines. Commonest prescription opioid was pentazocine used by 87 per cent of the women. Twenty two (71%) women were introduced to opioid by medical practitioners and commonest reason for introduction was pain (among 48%). Common co-occurring psychiatric diagnoses were depressive disorder (26%), cluster B traits/disorder (19%) and somatoform disorder (13%). Eight women did not complete treatment and left against medical advice. Thirteen women were advised maintenance treatment, and 70 per cent of them were retained for at least six months. Our findings revealed a link between mental illness, pain and non-medical use of prescription opioids among women. Majority of these women received opioids as a legitimate prescription form physician. Therefore, these legitimate prescribers should be trained for pain management to facilitate proper treatment of pain and to prevent the subsequent misuse of these medicines. Female patients with

  12. Further studies on the use of enzyme profiles to monitor residue accumulation in wildlife: Plasma enzymes in starlings fed graded concentrations of morsodren, DDE, Aroclor 1254, and malathion

    Science.gov (United States)

    Dieter, M.P.

    1975-01-01

    Wild-trapped starlings (Sturnus vulgaris) were fed concentrations of Morsodren (2, 4, and 8 ppm), DDE or Aroclor 1254 (5, 25, and 100 ppm), or malathion (8, 35, and 160 ppm) that were found to be sublethal in pen-reared Coturnix quail fed these amounts for 12 weeks. Plasma enzymes had to be measured earlier than planned in starlings fed Morsodren (at three weeks) or the organochlorine compounds (at seven weeks) because of unexpected, subsequent mortality. Variations in enzyme response were greater in wild than in pen-reared birds, but not enough to mask the toxicant-induced changes in enzyme activity. Cholinesterase activities decreased in birds fed Morsodren or malathion, and increased in those fed the organochlorine compounds. Lactate dehydrogenase activities increased two-fold in starlings fed Morsodren and two- to four-fold in those fed the organochlorine compounds, but only 50% in those fed malathion. Further examination of enzyme profiles showed that creatine kinase and aspartate aminotransferase activities increased two-to four-fold in birds fed Morsodren or the organochlorine compounds but not at all in those fed malathion. Thus the classes of environmental contaminants fed to starlings could be easily distinguished by these enzymatic parameters. Evaluation of enzymatic profiles appears to be a potentially valuable technique to monitor the presence of toxicants in wild populations, especially if used to complement standard chemical residue analyses. Here the residue analyses showed, after three weeks feeding, that mercury in the carcasses reflected the concentrations fed daily, whereas accumulation in the livers was two- to four-fold greater. After seven weeks feeding, liver residues of either organochlorine compound were about three-fold higher than the concentrations fed daily. However, four times as much DDE as Aroclor 1254 had accumulated in the carcasses.

  13. Gestodene and desogestrel do not have a different influence on concentration profiles of ethinylestradiol in women taking oral contraceptives--results of isotope dilution mass spectrometry measurements.

    Science.gov (United States)

    Siekmann, L; Siekmann, A; Bidlingmaier, F; Brill, K; Albring, M

    1998-08-01

    A new method for the quantitative determination of 17alpha-ethinylestradiol-17beta (EE2) in serum is presented here based on the principle of isotope dilution mass spectrometry (IDMS) with [13C]EE2 as internal standard. The technique was used to determine the concentration profiles of EE2 in the serum of female subjects who had taken oral contraceptives with different progestin components. The method has proved to be very reliable with respect to trueness, specificity, precision and detection sensitivity and offers considerable advantages compared with the immunological methods of measurement used to date. Forty-seven female volunteers took two different oral contraceptives containing EE2 combined with different progestins in accordance with a cross-over design. After the administration of 30 microg EE2 combined with 75 microg gestodene (EE2/GSD) or 150 microg desogestrel (EE2/DES), blood samples were taken from the subjects on certain days and in certain previously specified cycles in the course of 12 h after medication. The biometric analysis of the results showed that the concentration profiles of EE2 were in their statistics, significantly equivalent after the administration of either of the two oral contraceptives. The sometimes contradictory results found in former studies after the administration of the different contraceptives were presumably due to the methodological shortcomings of the radioimmunological measurement technique. With the use of the highly accurate and specific technique of IDMS it can now be unequivocally established that the different progestins in the tested oral contraceptives have no influence on the bioavailability of EE2 (area under EE2 serum concentration curves, as usually defined in pharmacokinetics).

  14. Clinical Response to Donepezil in Mild and Moderate Dementia: Relationship to Drug Plasma Concentration and CYP2D6 and APOE Genetic Polymorphisms.

    Science.gov (United States)

    Miranda, Luís F J R; Gomes, Karina B; Tito, Pedro A L; Silveira, Josianne N; Pianetti, Gerson A; Byrro, Ricardo M D; Peles, Patrícia R H; Pereira, Fernando H; Santos, Thiago R; Assini, Arthur G; Ribeiro, Valéria V; Moraes, Edgar N; Caramelli, Paulo

    2017-01-01

    The clinical response to donepezil in patients with mild and moderate dementia was investigated in relation to the drug plasma concentration and APOE and CYP2D6 polymorphisms. In a prospective naturalistic observational study, 42 patients with Alzheimer's disease (AD) and AD with cerebrovascular disease who took donepezil (10 mg) for 12 months were evaluated. Their DNA was genotyped, and the donepezil plasma concentrations were measured after 3, 6, and 12 months. Good responders scored ≥-1 on the Mini-Mental State Examination at 12 months in comparison to the baseline score. The study results indicated the good response pattern was influenced by the concentration of donepezil, but not by APOE and CYP2D6 polymorphisms.

  15. Evaluation of the Expression Profile of Extrapyramidal Symptoms Due to Antipsychotics by Data Mining of Japanese Adverse Drug Event Report (JADER) Database.

    Science.gov (United States)

    Kose, Eiji; Uno, Kana; Hayashi, Hiroyuki

    2017-01-01

     Typical antipsychotics are easily expressed as adverse events such as extrapyramidal symptom (EPS). On the other hand, incidence of adverse events due to atypical antipsychotics is low. Therefore, currently, atypical antipsychotics are widely used to treat schizophrenia. However, it has been reported that there is no difference in the frequency of EPS in atypical and typical antipsychotics. This study aimed to evaluate the expression profile of EPS in atypical and typical antipsychotics treatment using the Japanese Adverse Drug Event Report (JADER) database. We analyzed reports of EPS in the JADER database and calculated the reporting odds ratio (ROR) of antipsychotics potentially associated with EPS. We applied the Weibull shape parameter to time-to-event data in the JADER database. Consequently, there was little information to distinguish between the ROR of atypical and typical antipsychotics. A significant difference related to the time of onset of EPS in both antipsychotics was not recognized. However, when comparing each drug, Paliperidone, Perospirone, Blonanserin, and Aripiprazole were relatively developed as EPS in the early stage. On the other hand, Risperidone, Clozapine, Olanzapine, and Quetiapine were developed as EPS not only at an early stage but also after long-term use. In addition, this finding was suggested from the result of the cumulative incidence of EPS in each drug and of the time-to-onset analysis using Weibull distribution. These findings may contribute to future clinical practice because we revealed the expression profile of EPS in treatment with atypical and typical antipsychotics.

  16. Comparison of concentrations of drugs between blood samples with and without fluoride additive-important findings for Δ9-tetrahydrocannabinol and amphetamine.

    Science.gov (United States)

    Wiedfeld, Christopher; Krueger, Julia; Skopp, Gisela; Musshoff, Frank

    2018-02-17

    Fluoride is a common stabilizing agent in forensic toxicology to avoid the frequent problem of degradation of drugs in blood samples especially described for cocaine. In cases only samples with addition of fluoride are available, it is a crucial question if also concentrations of common drugs other than cocaine (amphetamines, opiates and cannabinoids) are affected by fluoride. So far, there are only rare literature data available on discrepant results especially for Δ 9 -tetrahydrocannabinol (THC). In this study, comparative analysis of positive tested paired routine plasma/serum samples (n = 375), collected at the same time point (one device with and one without fluoride), was carried out with special focus on cannabinoids. Samples were measured with validated routine liquid chromatography-tandem mass spectrometry methods for THC, 11-hydroxy-THC (THC-OH), 11-nor-9-carboxy-THC (THC-COOH), cocaine, benzoylecgonine, ecgonine methyl ester, morphine, codeine, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine, and 3,4-methylenedioxyethylamphetamine, and results were statistically evaluated. Beside the expected stabilization effect on cocaine and the consequently reduced concentration of ecgonine methyl ester in fluoride samples, benzoylecgonine was elevated compared to respective samples without fluoride. Most importantly, new findings were significantly reduced mean concentrations of THC (- 17%), THC-OH (- 17%), and THC-COOH (- 22%) in fluoride samples. Mean amphetamine concentration was significantly higher in samples with the additive (+ 6%). For the other amphetamine type of drugs as well as for morphine and codeine, no significant differences could be seen. Whenever specified thresholds have been set, such as in most European countries, the use of different blood sample systems may result in a motorist being differently charged or prosecuted. The findings will support forensic toxicologists at the

  17. Influence of dietary copper concentrations on growth performance, serum lipid profiles, antioxidant defenses, and fur quality in growing-furring male blue foxes (Vulpes lagopus).

    Science.gov (United States)

    Liu, Z; Wu, X; Zhang, T; Cui, H; Guo, J; Guo, Q; Gao, X; Yang, F

    2016-03-01

    A 75-d experiment was conducted to evaluate the influence of dietary Cu concentrations on growth performance, serum lipid profiles, antioxidant defenses, and fur quality in growing-furring male blue foxes. Seventy-five male blue foxes (5.78 ± 0.09 kg BW) were selected and randomly allocated to 1 of the following 5 dietary treatments: 1) control (basal diet without supplemental Cu; 7.78 mg Cu/kg), 2) 12.22 mg/kg supplemental Cu (Cu20), 3) 32.22 mg/kg supplemental Cu, 4) 72.22 mg/kg supplemental Cu (Cu80), and 5) 152.22 mg/kg supplemental Cu (Cu160). A dry feed that consisted of animal meals, soybean meal, extruded corn, and soybean oil was used as the basal diet and Cu was supplemented as reagent grade CuSO∙5HO. The results showed that Cu supplementation increased the ADG ( 0.10). Additionally, Cu supplementation linearly increased the concentration of fecal Cu, liver Cu, serum total protein, and albumin ( < 0.01). Foxes in the Cu160 group had higher serum Cu concentration than those in the control and Cu20 groups ( < 0.05). The concentration of serum cholesterol decreased with dietary Cu supplementation ( < 0.05). Serum high-density lipoprotein, on the contrary, tended to increase with Cu supplementation ( = 0.09). Copper supplementation increased the activity of glutathione peroxidase ( < 0.05) and tended to increase the activity of serum ceruloplasmin ( = 0.07). For fur quality, skin length in the Cu80 group was greater than that in the control and Cu20 groups. In addition, hair color tended to deepen with the increasing of dietary Cu concentrations ( = 0.08). In conclusion, this study demonstrates that Cu supplementation can promote growth and increase fat digestibility and fur length. Additionally, dietary Cu supplementation can enhance antioxidant capacity and reduce serum cholesterol in growing-furring blue foxes.

  18. AIDS Diarrhea and Antiretroviral Drug Concentrations: A Matched-Pair Cohort Study in Port au Prince, Haiti

    Science.gov (United States)

    Dillingham, Rebecca; Leger, Paul; Beauharnais, Carole-Anne; Miller, Erica; Kashuba, Angela; Jennings, Steven; Dupnik, Kathryn; Samie, Amidou; Eyma, Etna; Guerrant, Richard; Pape, Jean; Fitzgerald, Daniel

    2011-01-01

    Diarrhea in patients with acquired immunodeficiency syndrome (AIDS) may cause malabsorption of medications and failure of antiretroviral therapy (ART). We prospectively evaluated human immunodeficiency virus-1 (HIV-1)-infected patients with and without chronic diarrhea initiating ART in Haiti. We report mean plasma antiretroviral concentrations at 2 and 4 weeks. We measured plasma HIV-1 RNA levels at four points. Fifty-two HIV-1-infected patients (26 matched pairs) were enrolled. No differences in antiretroviral concentrations were detected. At week 24, 18/25 (72%) cases and 16/24 (68%) controls had undetectable plasma HIV-1 RNA levels (P = 0.69). Patients with plasma HIV-1 RNA levels > 50 copies/mL at week 24 had lower early efavirenz concentrations than patients with undetectable HIV-1 RNA (2,621 ng/mL versus 5,278 ng/mL; P = 0.02). Diarrhea at ART initiation does not influence plasma concentrations of the medications evaluated. Virologic outcome at Week 24 does correlate with efavirenz concentrations early in therapy but not with the presence of chronic diarrhea. PMID:21633022

  19. Protein profile and alpha-lactalbumin concentration in the milk of standard and transgenic goats expressing recombinant human butyrylcholinesterase.

    Science.gov (United States)

    Baldassarre, H; Schirm, M; Deslauriers, J; Turcotte, C; Bordignon, V

    2009-08-01

    The expression of recombinant proteins of pharmaceutical interest in the milk of transgenic farm animals can result in phenotypes exhibiting compromised lactation performance, as a result of the extraordinary demand placed on the mammary gland. In this study, we investigated differences in the protein composition of milk from control and transgenic goats expressing recombinant human butyrylcholinesterase. In Experiment 1, the milk was characterized by gel electrophoresis and liquid chromatography/mass spectrometry in order to identify protein bands that were uniquely visible in the transgenic milk and/or at differing band densities compared with controls. Differences in protein content were additionally evaluated by computer assisted band densitometry. Proteins identified in the transgenic milk only included serum proteins (i.e. complement component 3b, ceruloplasmin), a cytoskeleton protein (i.e. actin) and a stress-induced protein (94 kDA glucose-regulated protein). Proteins exhibiting evident differences in band density between the transgenic and control groups included immunoglobulins, serum albumin, beta-lactoglobulin and alpha-lactalbumin. These results were found to be indicative of compromised epithelial tight junctions, premature mammary cell death, and protein synthesis stress resulting from transgene expression. In Experiment 2, the concentration of alpha-lactalbumin was determined using the IDRing assay and was found to be significantly reduced on day 1 of lactation in transgenic goats (4.33 +/- 0.97 vs. 2.24 +/- 0.25 mg/ml, P 0.05). We concluded that a decreased/delayed expression of the alpha-lactalbumin gene may be the cause for the delayed start of milk production observed in this herd of transgenic goats.

  20. Ex vivo drug sensitivity profiles of Plasmodium falciparum field isolates from Cambodia and Thailand, 2005 to 2010, determined by a histidine-rich protein-2 assay

    Directory of Open Access Journals (Sweden)

    Tyner Stuart D

    2012-06-01

    Full Text Available Abstract Background In vitro drug susceptibility assay of Plasmodium falciparum field isolates processed “immediate ex vivo” (IEV, without culture adaption, and tested using histidine-rich protein-2 (HRP-2 detection as an assay, is an expedient way to track drug resistance. Methods From 2005 to 2010, a HRP-2 in vitro assay assessed 451 P. falciparum field isolates obtained from subjects with malaria in western and northern Cambodia, and eastern Thailand, processed IEV, for 50% inhibitory concentrations (IC50 against seven anti-malarial drugs, including artesunate (AS, dihydroartemisinin (DHA, and piperaquine. Results In western Cambodia, from 2006 to 2010, geometric mean (GM IC50 values for chloroquine, mefloquine, quinine, AS, DHA, and lumefantrine increased. In northern Cambodia, from 2009–2010, GM IC50 values for most drugs approximated the highest western Cambodia GM IC50 values in 2009 or 2010. Conclusions Western Cambodia is associated with sustained reductions in anti-malarial drug susceptibility, including the artemisinins, with possible emergence, or spread, to northern Cambodia. This potential public health crisis supports continued in vitro drug IC50 monitoring of P. falciparum isolates at key locations in the region.

  1. Contamination Profiles and Mass Loadings of Macrolide Antibiotics and Illicit Drugs from a Small Urban Wastewater Treatment Plant

    Science.gov (United States)

    Information is limited regarding sources, distribution, environmental behavior, and fate of prescribed and illicit drugs. Wastewater treatment plant (WWTP) effluents can be one of the sources of pharmaceutical and personal care products (PPCP) into streams, rivers and lakes. The ...

  2. Distinctive Drug-resistant Mutation Profiles and Interpretations of HIV-1 Proviral DNA Revealed by Deep Sequencing in Reverse Transcriptase.

    Science.gov (United States)

    Yin, Qian Qian; Li, Zhen Peng; Zhao, Hai; Pan, Dong; Wang, Yan; Xu, Wei Si; Xing, Hui; Feng, Yi; Jiang, Shi Bo; Shao, Yi Ming; Ma, Li Ying

    2016-04-01

    To investigate distinctive features in drug-resistant mutations (DRMs) and interpretations for reverse transcriptase inhibitors (RTIs) between proviral DNA and paired viral RNA in HIV-1-infected patients. Forty-three HIV-1-infected individuals receiving first-line antiretroviral therapy were recruited to participate in a multicenter AIDS Cohort Study in Anhui and Henan Provinces in China in 2004. Drug resistance genotyping was performed by bulk sequencing and deep sequencing on the plasma and whole blood of 77 samples, respectively. Drug-resistance interpretation was compared between viral RNA and paired proviral DNA. Compared with bulk sequencing, deep sequencing could detect more DRMs and samples with DRMs in both viral RNA and proviral DNA. The mutations M184I and M230I were more prevalent in proviral DNA than in viral RNA (Fisher's exact test, PDNA, and 5 of these samples with different DRMs between proviral DNA and paired viral RNA showed a higher level of drug resistance to the first-line drugs. Considering 'minority resistant variants', 22 samples (28.57%) were associated with a higher level of drug resistance to the tested RTIs for proviral DNA when compared with paired viral RNA. Compared with viral RNA, the distinctive information of DRMs and drug resistance interpretations for proviral DNA could be obtained by deep sequencing, which could provide more detailed and precise information for drug resistance monitoring and the rational design of optimal antiretroviral therapy regimens. Copyright © 2016 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  3. Analytical Profiling of Airplane Wastewater - a New Matrix for Mapping Worldwide Patterns of Drug Use and Abuse

    Directory of Open Access Journals (Sweden)

    Mardal Marie

    2017-06-01

    Full Text Available There is limited knowledge on the global prescription and consumption patterns of therapeutic (TD and illicit drugs (ID. Pooled urine analysis and wastewater-based epidemiology (WBE has been used for local-based drug screening. It is, however, difficult to study the global epidemiology due to difficulties in obtaining samples. The aims of the study were to test the detectability of TD and ID in airplane wastewater samples categorized according to their geographical origin.

  4. Risk factors for virological failure and subtherapeutic antiretroviral drug concentrations in HIV-positive adults treated in rural northwestern Uganda

    Directory of Open Access Journals (Sweden)

    Ahoua Laurence

    2009-06-01

    Full Text Available Abstract Background Little is known about immunovirological treatment outcomes and adherence in HIV/AIDS patients on antiretroviral therapy (ART treated using a simplified management approach in rural areas of developing countries, or about the main factors influencing those outcomes in clinical practice. Methods Cross-sectional immunovirological, pharmacological, and adherence outcomes were evaluated in all patients alive and on fixed-dose ART combinations for 24 months, and in a random sample of those treated for 12 months. Risk factors for virological failure (>1,000 copies/ml and subtherapeutic antiretroviral (ARV concentrations were investigated with multiple logistic regression. Results At 12 and 24 months of ART, 72% (n = 701 and 70% (n = 369 of patients, respectively, were alive and in care. About 8% and 38% of patients, respectively, were diagnosed with immunological failure; and 75% and 72% of patients, respectively, had undetectable HIV RNA (1,000 copies/ml were poor adherence, tuberculosis diagnosed after ART initiation, subtherapeutic NNRTI concentrations, general clinical symptoms, and lower weight than at baseline. About 14% of patients had low ARV plasma concentrations. Digestive symptoms and poor adherence to ART were risk factors for low ARV plasma concentrations. Conclusion Efforts to improve both access to care and patient management to achieve better immunological and virological outcomes on ART are necessary to maximize the duration of first-line therapy.

  5. Life-cycle exposure of fathead minnows to environmentally relevant concentrations of the β-blocker drug propranolol.

    Science.gov (United States)

    Parrott, Joanne L; Balakrishnan, Vimal K

    2017-06-01

    Propranolol is a human pharmaceutical β-blocker that has been detected in municipal wastewater effluents at ng/L to low μg/L. To assess the potential of this compound to affect fish, fathead minnow (Pimephales promelas) were exposed for a life cycle in a flow-through system to nominal propranolol concentrations of 0.87 ng/L, 8.7 ng/L, 87 ng/L, 870 ng/L, and 8700 ng/L. Measured propranolol concentrations were below detection for the 2 lowest exposure concentrations, and were 76 ng/L, 580 ng/L, and 7800 ng/L for the 3 highest exposure concentrations. During the 162-d to 165-d exposure, no significant changes in weights or lengths were seen in fathead minnows, although the highest concentration of propranolol did cause a 15% decrease in survival of larval and juvenile stage fish compared with controls. At maturity, there were no significant changes in condition factor, liver-somatic index, or secondary sex characteristics in propranolol-exposed male or female fish. Female gonadosomatic index was significantly decreased in fish exposed to the highest concentrations of propranolol, probably because of increased egg-laying. Fathead minnows from all propranolol exposures produced more eggs than control fish, with fish exposed to 7800 ng/L propranolol producing 70% more eggs per female (p = 0.060), and having significantly increased clutch size (p = 0.008). Egg quality, % fertilization, % hatching, and % deformities in F1 fry were unaffected by propranolol exposure of fish. Propranolol exposure caused no effects in fathead minnows, except at the highest exposure concentration (7800 ng/L), where there were slight decreases in survival of juvenile minnows, and indications of increased reproduction. The present study is important because it is the first to assess the potential for effects in fish exposed to propranolol for a life cycle. Environ Toxicol Chem 2017;36:1644-1651. © 2016 SETAC. © 2016 SETAC.

  6. Monitoring the concentrations of nonsteroidal anti-inflammatory drugs and cyclooxygenase-inhibiting activities in the surface waters of the Tone Canal and Edo River Basin.

    Science.gov (United States)

    Nishi, Iwaki; Kawakami, Tsuyoshi; Onodera, Sukeo

    2015-01-01

    Environmental pollution by pharmaceuticals has become a major problem in many countries worldwide. However, little is known about the concentrations of pharmaceuticals in water sources in Japan. The objective of this study was to clarify variations in the concentrations of seven nonsteroidal anti-inflammatory drugs (NSAIDs) and in cyclooxygenase(COX)-inhibiting activities in river water and domestic wastewater collected from the Tone Canal and the Edo River Basin in Japan. Total NSAID concentrations were higher in the Tone Canal than in the Edo River, and the highest concentration was observed at the domestic wastewater inflow point located in the Tone Canal (concentration averages of salicylic acid, ibuprofen, felbinac, naproxen, mefenamic acid, diclofenac, and ketoprofen in wastewater samples were 55.3, 162.9, 39.7, 11.8, 30.8, 259.7, and 48.3 ng L(-1), respectively). Gas chromatography-tandem mass spectrometry showed that wastewater samples collected during cooler seasons contained higher levels of COX-inhibiting activity. COX-inhibiting activities were highly correlated with NSAID concentrations (particularly for ketoprofen and diclofenac); however, other COX inhibitors, such as NSAIDs that were not examined in this study and/or other chemicals with COX-inhibiting activity, could exist in the water samples because the concentrations of NSAIDs obtained from the water samples did not account for the total COX-inhibiting activities observed. Therefore, COX inhibition assays may be helpful for evaluating the aquatic toxicity of COX inhibitors. In this study, we demonstrated that COX inhibitors in surface water may influence aquatic organisms more than was expected based on NSAID concentrations. Thus, further studies examining other COX inhibitors in the aquatic environment are necessary.

  7. Anatomy of a turbidity current: Concentration and grain size structure of a deep-sea flow revealed by multiple-frequency acoustic profilers

    Science.gov (United States)

    Simmons, S.; Parsons, D. R.; Paull, C. K.; Barry, J.; Chaffey, M. R.; Gwiazda, R.; O'Reilly, T. C.; Maier, K. L.; Rosenberger, K. J.; Talling, P.; Xu, J.

    2017-12-01

    Turbidity currents are responsible for transporting large volumes of sediment to the deep ocean, yet remain poorly understood due to the limited number of field observations of these episodic, high energy events. As part of the Monterey Coordinated Canyon Experiment high resolution, sub-minute acoustic velocity and backscatter profiles were acquired with downward-looking acoustic Doppler current profilers (ADCPs) distributed along the canyon on moorings at depths ranging from 270 to 1,900 m over a period of 18 months. Additionally, three upward-looking ADCPs on different frequencies (300, 600 and 1200 kHz) profiled the water column above a seafloor instrument node (SIN) at 1850 m water depth. Traps on the moorings collected sediment carried by the flows at different heights above the seafloor and sediment cores were taken to determine the depositional record produced by the flows. Several sediment-laden turbidity flows were observed during the experiment, three of which ran out for more than 50 km to water depths of greater than 1,900 m and were observed on all of the moorings. Flow speeds of up to 6 m/s were observed and individual moorings, anchored by railroad wheels, moved up to 7.8 km down-canyon during these powerful events. We present results based on a novel analysis of the multiple-frequency acoustic data acquired by the ADCPs at the SIN integrated with grain size data from the sediment traps, close to the deepest mooring in the array where the flow thickened to the 70 m height of the ADCP above the bed. The analysis allows, for the first time, retrieval of the suspended sediment concentration and vertical distribution of grain size structure within a turbidity in spectacular detail. The details of the stratification and flow dynamics will be used to re-evaluate and discuss our existing models for these deep-sea flows.

  8. Profile-QSAR 2.0: Kinase Virtual Screening Accuracy Comparable to Four-Concentration IC50s for Realistically Novel Compounds.

    Science.gov (United States)

    Martin, Eric J; Polyakov, Valery R; Tian, Li; Perez, Rolando C

    2017-08-28

    While conventional random forest regression (RFR) virtual screening models appear to have excellent accuracy on random held-out test sets, they prove lacking in actual practice. Analysis of 18 historical virtual screens showed that random test sets are far more similar to their training sets than are the compounds project teams actually order. A new, cluster-based "realistic" training/test set split, which mirrors the chemical novelty of real-life virtual screens, recapitulates the poor predictive power of RFR models in real projects. The original Profile-QSAR (pQSAR) method greatly broadened the domain of applicability over conventional models by using as independent variables a profile of activity predictions from all historical assays in a large protein family. However, the accuracy still fell short of experiment on realistic test sets. The improved "pQSAR 2.0" method replaces probabilities of activity from naïve Bayes categorical models at several thresholds with predicted IC 50 s from RFR models. Unexpectedly, the high accuracy also requires removing the RFR model for the actual assay of interest from the independent variable profile. With these improvements, pQSAR 2.0 activity predictions are now statistically comparable to medium-throughput four-concentration IC 50 measurements even on the realistic test set. Beyond the yes/no activity predictions from a typical high-throughput screen (HTS) or conventional virtual screen, these semiquantitative IC 50 predictions allow for predicted potency, ligand efficiency, lipophilic efficiency, and selectivity against antitargets, greatly facilitating hitlist triaging and enabling virtual screening panels such as toxicity panels and overall promiscuity predictions.

  9. Short communication: Effects of lysolecithin on milk fat synthesis and milk fatty acid profile of cows fed diets differing in fiber and unsaturated fatty acid concentration.

    Science.gov (United States)

    Rico, D E; Ying, Y; Harvatine, K J

    2017-11-01

    Thirteen multiparous Holstein cows were used in a crossover design that tested the effect of lysolecithin in diets differing in neutral detergent fiber (NDF) and unsaturated fatty acid (FA) concentrations. Experimental periods were 20 d in length and included two 10-d phases. A standard fiber and lower fat diet was fed the first 10 d (30.5% NDF, no added oil, lower-risk phase) and a lower NDF and higher oil diet was fed during the second 10 d (29.0% NDF and 2% oil from whole soybeans and soybean oil, high-risk phase). Treatments were control and 10 g/d of lysolecithin (LYSO) extended in a ground corn carrier. Milk was sampled on d 0, 5, and 10 of each phase for determination of fat and protein concentration and FA profile. We found no effect of treatment or treatment by time interaction for dry matter intake, milk yield, or milk protein concentration. A treatment by time interaction was observed for milk fat concentration and yield. Milk fat concentration was higher in LYSO on d 5 of the lower-risk phase, but decreased progressively in both treatments during the high-risk phase. Milk fat yield was not different among treatments during the lower-risk phase, but was lower in LYSO on d 15 and tended to be lower on d 20 during the high-risk phase. Concentrations of milk de novo FA decreased and preformed FA increased during the high-risk phase, but we found no effect of treatment or treatment by time interactions. We noted an effect of time, but no treatment or treatment by time interactions for milk trans FA isomers. Briefly, trans-11 C18:1 and cis-9,trans-11 conjugated linoleic acid progressively decreased as trans-10 C18:1 and trans-10,cis-12 conjugated linoleic acid progressively increased during the high-risk phase. The LYSO increased milk fat concentration when feeding a higher fiber and lower unsaturated FA diet, but decreased milk fat yield when feeding a lower fiber and higher unsaturated FA diet, although biohydrogenation pathways and capacity did not appear

  10. Andrographis paniculata Extract and Andrographolide Modulate the Hepatic Drug Metabolism System and Plasma Tolbutamide Concentrations in Rats

    Directory of Open Access Journals (Sweden)

    Haw-Wen Chen

    2013-01-01

    Full Text Available Andrographolide is the most abundant terpenoid of A. paniculata which is used in the treatment of diabetes. In this study, we investigated the effects of A. paniculata extract (APE and andrographolide on the expression of drug-metabolizing enzymes in rat liver and determined whether modulation of these enzymes changed the pharmacokinetics of tolbutamide. Rats were intragastrically dosed with 2 g/kg/day APE or 50 mg/kg/day andrographolide for 5 days before a dose of 20 mg/kg tolbutamide was given. APE and andrographolide reduced the AUC0–12 h of tolbutamide by 37% and 18%, respectively, compared with that in controls. The protein and mRNA levels and enzyme activities of CYP2C6/11, CYP1A1/2, and CYP3A1/2 were increased by APE and andrographolide. To evaluate whether APE or andrographolide affected the hypoglycemic action of tolbutamide, high-fat diet-induced obese mice were used and treated in the same manner as the rats. APE and andrographolide increased CYP2C6/11 expression and decreased plasma tolbutamide levels. In a glucose tolerance test, however, the hypoglycemic effect of tolbutamide was not changed by APE or andrographolide. These results suggest that APE and andrographolide accelerate the metabolism rate of tolbutamide through increased expression and activity of drug-metabolizing enzymes. APE and andrographolide, however, do not impair the hypoglycemic effect of tolbutamide.

  11. Intrapartum tenofovir and emtricitabine reduces low-concentration drug resistance selected by single-dose nevirapine for perinatal HIV prevention.

    Science.gov (United States)

    Chi, Benjamin H; Ellis, Giovanina M; Chintu, Namwinga; Cantrell, Ronald A; Sinkala, Moses; Aldrovandi, Grace M; Warrier, Ranjit; Mbewe, Felistas; Nakamura, Kyle; Stringer, Elizabeth M; Frenkel, Lisa M; Stringer, Jeffrey S A

    2009-11-01

    A single dose of tenofovir/emtricitabine (TDF/FTC) during labor significantly reduces peripartum nevirapine-associated viral drug resistance when measured by consensus HIV sequencing. It is unknown whether this effect extends to HIV subpopulations of or = 2% of the viral population, we used an oligonucleotide ligation assay (OLA) at codons 103, 106, 181, and 190 of HIV reverse transcriptase. To assess development of drug resistance mutations to our study intervention, OLA was also performed at codons 65 and 184. Among the 328 women included in the 2-week analysis, those receiving TDF/FTC were less likely to have NNRTI resistance by OLA (RR = 0.40, 95% CI = 0.21-0.77). A similar trend was observed among the 315 women included in the 6-week analysis (RR = 0.45, 95% CI = 0.31-0.66). Only two (1%) specimens had detectable K65R by OLA. Both were at 6 weeks postpartum; one was detected in the intervention arm and one in the control arm (p = 0.96). M184V was not detected. The ability of single-dose TDF/FTC to protect against peripartum NVP-induced NNRTI resistance extends to minority populations. This efficacy is achieved without significant selection of TDF- or FTC-resistant viruses.

  12. Development of 1.6  μm DIAL using an OPG/OPA transmitter for measuring atmospheric CO2 concentration profiles.

    Science.gov (United States)

    Shibata, Yasukuni; Nagasawa, Chikao; Abo, Makoto

    2017-02-01

    An experiment for the measurement of atmospheric CO2 vertical profiles up to a 7 km altitude was successfully conducted using a 1.6 μm ground-based differential absorption Lidar developed by Tokyo Metropolitan University. To achieve a high pulse repetition rate, large power output, and high frequency stabilization, we developed a new 1.6 μm Lidar system using an optical parametric generator (OPG) transmitter. Unlike the previous system's transmitter, OPG does not need a resonator. We amplified its output with two optical parametric amplifiers. We validated our system against an in situ sensor and found the difference between their CO2 concentration measurements to be 0.06 ppm.

  13. Metabolic profiling and flux analysis of MEL-2 human embryonic stem cells during exponential growth at physiological and atmospheric oxygen concentrations.

    Directory of Open Access Journals (Sweden)

    Jennifer Turner

    Full Text Available As human embryonic stem cells (hESCs steadily progress towards regenerative medicine applications there is an increasing emphasis on the development of bioreactor platforms that enable expansion of these cells to clinically relevant numbers. Surprisingly little is known about the metabolic requirements of hESCs, precluding the rational design and optimisation of such platforms. In this study, we undertook an in-depth characterisation of MEL-2 hESC metabolic behaviour during the exponential growth phase, combining metabolic profiling and flux analysis tools at physiological (hypoxic and atmospheric (normoxic oxygen concentrations. To overcome variability in growth profiles and the problem of closing mass balances in a complex environment, we developed protocols to accurately measure uptake and production rates of metabolites, cell density, growth rate and biomass composition, and designed a metabolic flux analysis model for estimating internal rates. hESCs are commonly considered to be highly glycolytic with inactive or immature mitochondria, however, whilst the results of this study confirmed that glycolysis is indeed highly active, we show that at least in MEL-2 hESC, it is supported by the use of oxidative phosphorylation within the mitochondria utilising carbon sources, such as glutamine to maximise ATP production. Under both conditions, glycolysis was disconnected from the mitochondria with all of the glucose being converted to lactate. No difference in the growth rates of cells cultured under physiological or atmospheric oxygen concentrations was observed nor did this cause differences in fluxes through the majority of the internal metabolic pathways associated with biogenesis. These results suggest that hESCs display the conventional Warburg effect, with high aerobic activity despite high lactate production, challenging the idea of an anaerobic metabolism with low mitochondrial activity. The results of this study provide new insight that

  14. Using a two site-reactive model for simulating one century changes of Zn and Pb concentration profiles in soils affected by metallurgical fallout

    International Nuclear Information System (INIS)

    Kochem Mallmann, Fábio Joel; Rheinheimer dos Santos, Danilo; Cambier, Philippe; Labanowski, Jérôme; Lamy, Isabelle; Santanna, Maria Alice; Tessier, Daniel; Oort, Folkert van

    2012-01-01

    Predicting the transfer of contaminants in soils is often hampered by lacking validation of mathematical models. Here, we applied Hydrus-2D software to three agricultural soils for simulating the 1900–2005 changes of zinc and lead concentration profiles derived from industrial atmospheric deposition, to validate the tested models with plausible assumptions on past metal inputs to reach the 2005 situation. The models were set with data from previous studies on the geochemical background, estimated temporal metal deposition, and the 2005 metal distributions. Different hypotheses of chemical reactions of metals with the soil solution were examined: 100% equilibrium or partial equilibrium, parameterized following kinetic chemical extractions. Finally, a two-site model with kinetic constant values adjusted at 1% of EDTA extraction parameters satisfactory predicted changes in metal concentration profiles for two arable soils. For a grassland soil however, this model showed limited applicability by ignoring the role of earthworm activity in metal incorporation. - Highlights: ► We modeled 100-year changes of Zn and Pb in agricultural soils with Hydrus-2D. ► Different hypotheses of chemical reactions of metals – soil solution were tested. ► We used a two-site model with kinetic constants adjusted to 1% of EDTA extractions. ► Satisfactory prediction in arable soils; earthworm activity ignored under grassland. ► Land use must be considered consider when modeling metal pollutant transfer in soils. - Hydrus simulates Zn and Pb distributions in soils horizons of arable land, when a two-site model with adjusted kinetic parameters is used

  15. Effects of SULT1A1 Copy Number Variation on Estrogen Concentration and Tamoxifen-Associated Adverse Drug Reactions in Premenopausal Thai Breast Cancer Patients: A Preliminary Study.

    Science.gov (United States)

    Charoenchokthavee, Wanaporn; Ayudhya, Duangchit Panomvana Na; Sriuranpong, Virote; Areepium, Nutthada

    2016-01-01

    Tamoxifen is a pharmacological estrogen inhibitor that binds to the estrogen receptor (ER) in breast cells. However, it shows an estrogenic effect in other organs, which causes adverse drug reactions (ADRs). The sulfotransferase 1A1 (SULT1A1) enzyme encoded by the SULT1A1 gene is involved in estrogen metabolism. Previous research has suggested that the SULT1A1 copy number is linked with the plasma estradiol (E2) concentration. Here, a total of 34 premenopausal breast cancer patients, selected from the Thai Tamoxifen (TTAM) Project, were screened for their SULT1A1 copy number, plasma E2 concentration and ADRs. The mean age was 44.3±11.1 years, and they were subtyped as ER+/ progesterone receptor (PR) + (28 patients), ER+/ PR- (5 patients) and ER-/PR- (1 patient). Three patients reported ADRs, which were irregular menstruation (2 patients) and vaginal discharge (1 patient). Most (33) patients had two SULT1A1 copies, with one patient having three copies. The median plasma E2 concentration was 1,575.6 (IQR 865.4) pg/ml. Patients with ADRs had significantly higher plasma E2 concentrations than those patients without ADRs (p = 0.014). The plasma E2 concentration was numerically higher in the patient with three SULT1A1 copies, but this lacked statistical significance.

  16. 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

  17. The dynamic ocean biological pump: Insights from a global compilation of particulate organic carbon, CaCO3, and opal concentration profiles from the mesopelagic

    Science.gov (United States)

    Lam, Phoebe J.; Doney, Scott C.; Bishop, James K. B.

    2011-09-01

    We have compiled a global data set of 62 open ocean profiles of particulate organic carbon (POC), CaCO3, and opal concentrations collected by large volume in situ filtration in the upper 1000 m over the last 30 years. We define concentration-based metrics for the strength (POC concentration at depth) and efficiency (attenuation of POC with depth in the mesopelagic) of the biological pump. We show that the strength and efficiency of the biological pump are dynamic and are characterized by a regime of constant and high transfer efficiency at low to moderate surface POC and a bloom regime where the height of the bloom is characterized by a weak deep biological pump and low transfer efficiency. The variability in POC attenuation length scale manifests in a clear decoupling between the strength of the shallow biological pump (e.g., POC at the export depth) and the strength of the deep biological pump (POC at 500 m). We suggest that the paradigm of diatom-driven export production is driven by a too restrictive perspective on upper mesopelagic dynamics. Indeed, our full mesopelagic analysis suggests that large, blooming diatoms have low transfer efficiency and thus may not export substantially to depth; rather, our analysis suggests that ecosystems characterized by smaller cells and moderately high %CaCO3 have a high mesopelagic transfer efficiency and can have higher POC concentrations in the deep mesopelagic even with relatively low surface or near-surface POC. This has negative implications for the carbon sequestration prospects of deliberate iron fertilization.

  18. Viability of primary osteoblasts after treatment with tenofovir alafenamide: Lack of cytotoxicity at clinically relevant drug concentrations.

    Directory of Open Access Journals (Sweden)

    Christian Callebaut

    Full Text Available Tenofovir alafenamide (TAF is a phosphonoamidate prodrug of the nucleotide HIV reverse transcriptase inhibitor tenofovir (TFV. TAF is approved for the treatment of HIV-1 infection as part of the single-tablet regimen containing elvitegravir, cobicistat, emtricitabine, and TAF. When dosed once-daily, TAF results in approximately 90% lower levels of plasma TFV and a 4-fold increase in intracellular TFV-diphosphate (TFV-DP in PBMCs compared with the TFV prodrug tenofovir disoproxil fumarate (TDF. Several antiretrovirals, including TDF, have been associated with bone mineral density decreases in patients; the effect of clinically relevant TAF concentrations on primary osteoblast viability was therefore assessed in vitro. Studies in PBMCs determined that a 2-hour TAF exposure at concentrations similar to human plasma Cmax achieved intracellular TFV-DP levels comparable to those observed after the maximum recommended human dose of 25 mg TAF. Comparable intracellular TFV-DP levels were achieved in primary osteoblasts with 2-hour TAF exposure daily for 3 days at concentrations similar to those used for PBMCs (100-400 nM. No change in cell viability was observed in either primary osteoblasts or PBMCs. The mean TAF CC50 in primary osteoblasts after 3 days of daily 2-hour pulses was >500 μM, which is >1033 times higher than the TAF maximum recommended human dose plasma Cmax. In summary, primary osteoblasts were not preferentially loaded by TAF compared with PBMCs, with comparable TFV-DP levels achieved in both cell types. Furthermore, there was no impact on osteoblast cell viability at clinically relevant TAF concentrations.

  19. Evaluating vertical concentration profile of carbon source released from slow-releasing carbon source tablets and in situ biological nitrate denitrification activity

    Science.gov (United States)

    Yeum, Y.; HAN, K.; Yoon, J.; Lee, J. H.; Song, K.; Kang, J. H.; Park, C. W.; Kwon, S.; Kim, Y.

    2017-12-01

    Slow-releasing carbon source tablets were manufactured during the design of a small-scale in situ biological denitrification system to reduce high-strength nitrate (> 30 mg N/L) from a point source such as livestock complexes. Two types of slow-releasing tablets, precipitating tablet (PT, apparent density of 2.0 g/mL) and floating tablet (FT), were prepared to achieve a vertically even distribution of carbon source (CS) in a well and an aquifer. Hydroxypropyl methylcellulose (HPMC) was used to control the release rate, and microcrystalline cellulose pH 101 (MCC 101) was added as a binder. The #8 sand was used as a precipitation agent for the PTs, and the floating agents for the FTs were calcium carbonate and citric acid. FTs floated within 30 min. and remained in water because of the buoyance from carbon dioxide, which formed during the acid-base reaction between citric acid and calcium carbonate. The longevities of PTs with 300 mg of HPMC and FTs with 400 mg of HPMC were 25.4 days and 37.3 days, respectively. We assessed vertical CS profile in a continuous flowing physical aquifer model (release test, RT) and its efficiency on biological nitrate denitrification (denitrification test, DT). During the RT, PTs, FTs and a tracer (as 1 mg rhodamine B/L) were initially injected into a well of physical aquifer model (PAM). Concentrations of CS and the tracer were monitored along the streamline in the PAM to evaluate vertical profile of CS. During the DT, the same experiment was performed as RT, except continuous injection of solution containing 30 mg N/L into the PAM to evaluate biological denitrification activity. As a result of RT, temporal profiles of CS were similar at 3 different depths of monitoring wells. These results suggest that simultaneous addition of PT and FT be suitable for achieving a vertically even distribution of the CS in the injection well and an aquifer. In DT, similar profile of CS was detected in the injection well, and nitrate was biologically

  20. Prediction of Cytochrome P450 Profiles of Environmental Chemicals with QSAR Models Built from Drug-like Molecules

    Science.gov (United States)

    The human cytochrome P450 (CYP450) enzyme family is involved in the biotransformation of many environmental chemicals. As part of the U.S. Tox21 effort, we profiled the CYP450 activity of ~2800 chemicals predominantly of environmental concern against CYP1A2, CYP2C19, CYP2C9, CYP2...

  1. Property profiling of biosimilar mucus in a novel mucus-containing in vitro model for assessment of intestinal drug absorption

    DEFF Research Database (Denmark)

    Bøgh, Marie; Baldursdóttir, Stefania G; Müllertz, Anette

    2014-01-01

    to establish a more representative in vitro model for the intestinal mucosa. The rheological profile of a biosimilar mucus mixture composed of purified gastric mucin, lipids and protein in buffer was optimized by supplementing with an anionic polymer to display viscoelastic properties and a microstructure...

  2. Antimicrobial susceptibility profile of isolates of Aeromonas ...

    African Journals Online (AJOL)

    Antimicrobial susceptibility profile of 45 Aeromonas hydrophila isolates (from different sources) to 11 commonly used antimicrobial agents was determined by agar diffusion technique. Minimal inhibitory concentrations (MICs) of antimicrobial drugs were also determined using amylase property of Aeromonas as end-point ...

  3. 3D modeling of effects of increased oxygenation and activity concentration in tumors treated with radionuclides and antiangiogenic drugs

    Energy Technology Data Exchange (ETDEWEB)

    Lagerloef, Jakob H.; Kindblom, Jon; Bernhardt, Peter [Department of Radiation Physics, Goeteborg University, Goeteborg 41345 (Sweden); Department of Oncology, Sahlgrenska University Hospital, Goeteborg 41345 (Sweden); Department of Radiation Physics, Goeteborg University, Goeteborg, Sweden and Department of Nuclear Medicine, Sahlgrenska University Hospital, Goeteborg 41345 (Sweden)

    2011-08-15

    Purpose: Formation of new blood vessels (angiogenesis) in response to hypoxia is a fundamental event in the process of tumor growth and metastatic dissemination. However, abnormalities in tumor neovasculature often induce increased interstitial pressure (IP) and further reduce oxygenation (pO{sub 2}) of tumor cells. In radiotherapy, well-oxygenated tumors favor treatment. Antiangiogenic drugs may lower IP in the tumor, improving perfusion, pO{sub 2} and drug uptake, by reducing the number of malfunctioning vessels in the tissue. This study aims to create a model for quantifying the effects of altered pO{sub 2}-distribution due to antiangiogenic treatment in combination with radionuclide therapy. Methods: Based on experimental data, describing the effects of antiangiogenic agents on oxygenation of GlioblastomaMultiforme (GBM), a single cell based 3D model, including 10{sup 10} tumor cells, was developed, showing how radionuclide therapy response improves as tumor oxygenation approaches normal tissue levels. The nuclides studied were {sup 90}Y, {sup 131}I, {sup 177}Lu, and {sup 211}At. The absorbed dose levels required for a tumor control probability (TCP) of 0.990 are compared for three different log-normal pO{sub 2}-distributions: {mu}{sub 1} = 2.483, {sigma}{sub 1} = 0.711; {mu}{sub 2} = 2.946, {sigma}{sub 2} = 0.689; {mu}{sub 3} = 3.689, and {sigma}{sub 3} = 0.330. The normal tissue absorbed doses will, in turn, depend on this. These distributions were chosen to represent the expected oxygen levels in an untreated hypoxic tumor, a hypoxic tumor treated with an anti-VEGF agent, and in normal, fully-oxygenated tissue, respectively. The former two are fitted to experimental data. The geometric oxygen distributions are simulated using two different patterns: one Monte Carlo based and one radially increasing, while keeping the log-normal volumetric distributions intact. Oxygen and activity are distributed, according to the same pattern. Results: As tumor pO{sub 2

  4. Specific Clinical Profile and Risk Factors for Mortality in General Surgery Patients with Infections by Multi-Drug-Resistant Gram-Negative Bacteria.

    Science.gov (United States)

    Rubio-Perez, Ines; Martin-Perez, Elena; Domingo-García, Diego; Garcia-Olmo, Damian

    2017-07-01

    The incidence of gram-negative multi-drug-resistant (MDR) infections is increasing worldwide. This study sought to determine the incidence, clinical profiles, risk factors, and mortality of these infections in general surgery patients. All general surgery patients with a clinical infection by gram-negative MDR bacteria were studied prospectively for a period of five years (2007-2011). Clinical, surgical, and microbiologic parameters were recorded, with a focus on the identification of risk factors for MDR infection and mortality. Incidence of MDR infections increased (5.6% to 15.2%) during the study period; 106 patients were included, 69.8% presented nosocomial infections. Mean age was 65 ± 15 years, 61% male. Extended-spectrum β-lactamases (ESBL) Escherichia coli was the most frequent MDR bacteria. Surgical site infections and abscesses were the most common culture locations. The patients presented multiple pre-admission risk factors and invasive measures during hospitalization. Mortality was 15%, and related to older age (odds ratio [OR] 1.07), malnutrition (OR 13.5), chronic digestive conditions (OR 4.7), chronic obstructive pulmonary disease (OR 3.9), and surgical re-intervention (OR 9.2). Multi-drug resistant infections in the surgical population are increasing. The most common clinical profile is a 65-year-old male, with previous comorbidities, who has undergone a surgical intervention, intensive care unit (ICU) admission, and invasive procedures and who has acquired the MDR infection in the nosocomial setting.

  5. Mutations Conferring Resistance to Viral DNA Polymerase Inhibitors in Camelpox Virus Give Different Drug-Susceptibility Profiles in Vaccinia Virus

    Czech Academy of Sciences Publication Activity Database

    Duraffour, S.; Andrei, G.; Topalis, D.; Krečmerová, Marcela; Crance, J. M.; Garin, D.; Snoeck, R.

    2012-01-01

    Roč. 86, č. 13 (2012), s. 7310-7325 ISSN 0022-538X Institutional support: RVO:61388963 Keywords : camelpox virus * CMLV * vaccinia virus VACV * acyclic nucleoside phosphonates * HPMPDAP * cidofovir * drug resistance Subject RIV: CC - Organic Chemistry Impact factor: 5.076, year: 2012

  6. Organophosphate esters and phthalate esters in human hair from rural and urban areas, Chongqing, China: Concentrations, composition profiles and sources in comparison to street dust.

    Science.gov (United States)

    He, Ming-Jing; Lu, Jun-Feng; Ma, Jing-Ye; Wang, Huan; Du, Xiao-Fan

    2018-02-23

    Human hair and street dust from rural and urban areas in Chongqing were collected to analyze Organophosphate esters (OPEs) and phthalate esters (PAEs). Concentrations of OPEs in urban hair were significantly higher than those in rural hair, whereas PAEs concentrations in rural hair were significantly higher than those in urban hair. Different composition patterns of OPEs were observed in rural and urban hair, where tris (2-chloroisopropyl) phosphate (TCIPP), tris (butyl) phosphate (TNBP) and triphenyl phosphate (TPHP) were the dominating analogues in rural hair, accounting for 62.1% of the OPEs burden, and tris (methylphenyl) phosphate (TMPP) exhibited a high contribution in urban hair, responsible for 51.3% of total OPEs, which differed from the composition profiles in corresponding street dust. Analogous composition patterns of PAEs were found in hair of both areas. Di-(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DNBP), diisobutyl phthalate (DIBP) and diethyl phthalate (DEP) were the most abundant analogues in hair samples, while DEHP was the predominant analogue in dust samples. No clear tendency was obtained between the increasing ages and the concentrations of both compounds. Most OPEs and PAEs congeners showed significantly positive correlation with one another in rural hair. On the contrary, different correlation patterns were observed in urban hair for OPEs and PAEs, indicating multiple or additional sources existed in urban areas. Significant correlations of OPEs and PAEs were found between hair and corresponding street dust samples, but poor correlations of OPEs and PAEs were observed between rural hair and rural indoor dust, suggesting that street dust may be a predominant exogenous source for human exposure to OPEs and PAEs in this area. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Whole genome transcript profiling of drug induced steatosis in rats reveals a gene signature predictive of outcome.

    Directory of Open Access Journals (Sweden)

    Nishika Sahini

    Full Text Available Drug induced steatosis (DIS is characterised by excess triglyceride accumulation in the form of lipid droplets (LD in liver cells. To explore mechanisms underlying DIS we interrogated the publically available microarray data from the Japanese Toxicogenomics Project (TGP to study comprehensively whole genome gene expression changes in the liver of treated rats. For this purpose a total of 17 and 12 drugs which are diverse in molecular structure and mode of action were considered based on their ability to cause either steatosis or phospholipidosis, respectively, while 7 drugs served as negative controls. In our efforts we focused on 200 genes which are considered to be mechanistically relevant in the process of lipid droplet biogenesis in hepatocytes as recently published (Sahini and Borlak, 2014. Based on mechanistic considerations we identified 19 genes which displayed dose dependent responses while 10 genes showed time dependency. Importantly, the present study defined 9 genes (ANGPTL4, FABP7, FADS1, FGF21, GOT1, LDLR, GK, STAT3, and PKLR as signature genes to predict DIS. Moreover, cross tabulation revealed 9 genes to be regulated ≥10 times amongst the various conditions and included genes linked to glucose metabolism, lipid transport and lipogenesis as well as signalling events. Additionally, a comparison between drugs causing phospholipidosis and/or steatosis revealed 26 genes to be regulated in common including 4 signature genes to predict DIS (PKLR, GK, FABP7 and FADS1. Furthermore, a comparison between in vivo single dose (3, 6, 9 and 24 h and findings from rat hepatocyte studies (2 h, 8 h, 24 h identified 10 genes which are regulated in common and contained 2 DIS signature genes (FABP7, FGF21. Altogether, our studies provide comprehensive information on mechanistically linked gene expression changes of a range of drugs causing steatosis and phospholipidosis and encourage the screening of DIS signature genes at the preclinical stage.

  8. Effect of CLA supplementation to low-protein diets on the growth performance, carcass characteristics, plasma urea nitrogen concentration, and fatty acid profile in the meat of pigs

    Directory of Open Access Journals (Sweden)

    Manuel Martínez-Aispuro

    2014-10-01

    Full Text Available To analyze the effect of conjugated linoleic acid (CLA on the meat of pigs (0,1% and three crude protein (CP levels (nursery: 20.5, 16.0, 14.5%; growing: 16, 14.5, 11.5%; and finishing: 14.0, 12.5, 11% CP, studies were conducted with 36 hybrid (Yorkshire×Landrace×Duroc barrows (17.3-83.5 kg, which were individually penned and allotted in a completely randomized design in a factorial (2×3 arrangement for 84 d. The analysis by phases indicated that CP level affected some variables. Average daily gain, average daily feed intake, fat free lean gain, backfat thickness, longissimus muscle area and final body weight were reduced (P≤0.05 feeding the lowest CP diet in nursery and growing pigs. Plasma urea nitrogen concentration was also lower (P≤0.05 in the growing and finishing phases when fed the lowest CP level. The global analysis showed that all the analyzed variables (except feed gain ratio, lean meat percentage and plasma urea nitrogen concentration were reduced (P≤0.05 in the pigs fed low-protein diets; plasma urea nitrogen concentration tended to be lower (P=0.07 when CP was reduced. The fatty acid profile of the meat (semimembranosus and longissimus muscles indicated that CLA addition increased CLA isomers and total saturated fatty acids, and reduced the total monounsaturated fatty acids (P≤0.05. α-Linolenic acid was lowered in longissimus muscle of pigs fed LPD (P=0.08. These results indicated that reducing the crude protein concentration in the diet of fattening pigs from 20.5 to 16.0% in nursery phase; from 16.0 to 14.5% in growing stage; and from 14.0 to 12.5% in finishing pigs, did not negatively affect the growth performance, nor carcass characteristics. The results also showed that the addition of CLA did not improve pig response and the concentration of unsaturated fatty acids and total lipids altered the feeding LPD.

  9. The law of mass action and the pharmacological concentration-effect curve: resolving the paradox of apparently non-dose-related adverse drug reactions.

    Science.gov (United States)

    Aronson, Jeffrey K; Ferner, Robin E

    2016-01-01

    Adverse drug reactions are sometimes described as being 'non-dose-related' because no relationship has been found between increasing doses and either the intensity of the response or the proportion of individuals in whom the response occurs; furthermore, hypersensitivity reactions are often regarded as being non-dose-related, even if different doses have not been studied. However, the law of mass action implies that all pharmacological effects are concentration related and should increase in intensity with increasing dose. We set out to explain this paradox. We searched for published adverse drug reactions that have been described as non-dose-related and analysed them. We identified four categories of explanations that resolve the paradox: (i) the reaction is not real; it may have occurred by chance or there may be methodological problems, such as bias or confounding factors; (ii) the dose-response curve for the adverse effect reaches a maximum at doses lower than were studied (i.e. a hypersusceptibility reaction); this underpins the use of test doses to predict the possibility of an adverse reaction at therapeutic doses; (iii) susceptibility to the adverse reaction differs widely among individuals; and (iv) imprecision or inaccuracy in the measurement of either dose or effect obscures dose responsiveness. This last explanation encompasses: (a) reactions related to cumulative dose; (b) dissociation between dose and concentration through saturable pharmacokinetics; and (c) variability in the measurement of the effect. If an adverse drug reaction appears to be non-dose-related, the reasons should be sought, having these mechanisms in mind. © 2015 The British Pharmacological Society.

  10. Gonadotrophin stimulation in IVF alters the immune cell profile in follicular fluid and the cytokine concentrations in follicular fluid and serum.

    Science.gov (United States)

    Kollmann, Z; Schneider, S; Fux, M; Bersinger, N A; von Wolff, M

    2017-04-01

    Are the immune cell profiles and the cytokine concentrations in follicular fluid (FF) and serum at the preovulatory stage different in conventional exogenous gonadotrophin stimulated IVF (c-IVF) compared with natural cycle IVF (NC-IVF)? The cell counts of CD45+ leucocytes and T cell subpopulations and the cytokine concentrations in FF and serum are different in c-IVF compared to NC-IVF. FF-derived cells are heterogeneous. Immune cells are involved in intra-ovarian processes and cytokines are required for normal follicular development. Gonadotrophins stimulate the regulatory intrafollicular system and influence the local distribution of immune cells and the intrafollicular release of cytokines. Administration of exogenous gonadotrophins may have a significant effect on this local regulatory system, which then in turn could influence oocyte quality. The study included 105 patients, 69 undergoing c-IVF and 36 undergoing NC-IVF. c-IVF was performed by exogenous ovarian stimulation with hMG and GnRH antagonists. FF samples were collected from the first dominant follicle in c-IVF without pooling and from single leading preovulatory follicles in NC-IVF. Three different approaches were used to analyze FF samples: (i) microscopic investigation of CD45+ leucocytes, (ii) fluorescence-activated cell sorting to determine CD19+ B cells and CD3+ T cells including T cell subpopulations (CD4+, CD8+), and (iii) evaluation of tumour necrosis factor-alpha (TNF-α), interferon-gamma (INF-γ), interleukins (IL)-2, -6, -8, -10 and vascular endothelial growth factor (VEGF) levels in matched FF and serum samples using the Bio-Plex® platform. FF obtained from c-IVF contained proportionally more CD45+ leucocytes (P = 0.0384), but fewer CD8+ cytotoxic T cells than FF from NC-IVF. CD3+ T lymphocytes were the most common type of lymphocytes, and the number thereof was comparable in the two study groups. In c-IVF, serum VEGF levels were higher (P = 0.007) than in NC-IVF while FF contained

  11. Toward the establishment of standardized in vitro tests for lipid-based formulations. 2. The effect of bile salt concentration and drug loading on the performance of type I, II, IIIA, IIIB, and IV formulations during in vitro digestion.

    Science.gov (United States)

    Williams, Hywel D; Anby, Mette U; Sassene, Philip; Kleberg, Karen; Bakala-N'Goma, Jean-Claude; Calderone, Marilyn; Jannin, Vincent; Igonin, Annabel; Partheil, Anette; Marchaud, Delphine; Jule, Eduardo; Vertommen, Jan; Maio, Mario; Blundell, Ross; Benameur, Hassan; Carrière, Frédéric; Müllertz, Anette; Pouton, Colin W; Porter, Christopher J H

    2012-11-05

    The LFCS Consortium was established to develop standardized in vitro tests for lipid-based formulations (LBFs) and to examine the utility of these tests to probe the fundamental mechanisms that underlie LBF performance. In this publication, the impact of bile salt (sodium taurodeoxycholate, NaTDC) concentration and drug loading on the ability of a range of representative LBFs to generate and sustain drug solubilization and supersaturation during in vitro digestion testing has been explored and a common driver of the potential for drug precipitation identified. Danazol was used as a model poorly water-soluble drug throughout. In general, increasing NaTDC concentrations increased the digestion of the most lipophilic LBFs and promoted lipid (and drug) trafficking from poorly dispersed oil phases to the aqueous colloidal phase (AP(DIGEST)). High NaTDC concentrations showed some capacity to reduce drug precipitation, although, at NaTDC concentrations ≥3 mM, NaTDC effects on either digestion or drug solubilization were modest. In contrast, increasing drug load had a marked impact on drug solubilization. For LBFs containing long-chain lipids, drug precipitation was limited even at drug loads approaching saturation in the formulation and concentrations of solubilized drug in AP(DIGEST) increased with increased drug load. For LBFs containing medium-chain lipids, however, significant precipitation was evident, especially at higher drug loads. Across all formulations a remarkably consistent trend emerged such that the likelihood of precipitation was almost entirely dependent on the maximum supersaturation ratio (SR(M)) attained on initiation of digestion. SR(M) defines the supersaturation "pressure" in the system and is calculated from the maximum attainable concentration in the AP(DIGEST) (assuming zero precipitation), divided by the solubility of the drug in the colloidal phases formed post digestion. For LBFs where phase separation of oil phases did not occur, a

  12. Alterations in endo-lysosomal function induce similar hepatic lipid profiles in rodent models of drug-induced phospholipidosis and Sandhoff disease.

    Science.gov (United States)

    Lecommandeur, Emmanuelle; Baker, David; Cox, Timothy M; Nicholls, Andrew W; Griffin, Julian L

    2017-07-01

    Drug-induced phospholipidosis (DIPL) is characterized by an increase in the phospholipid content of the cell and the accumulation of drugs and lipids inside the lysosomes of affected tissues, including in the liver. Although of uncertain pathological significance for patients, the condition remains a major impediment for the clinical development of new drugs. Human Sandhoff disease (SD) is caused by inherited defects of the β subunit of lysosomal β-hexosaminidases (Hex) A and B, leading to a large array of symptoms, including neurodegeneration and ultimately death by the age of 4 in its most common form. The substrates of Hex A and B, gangliosides GM2 and GA2, accumulate inside the lysosomes of the CNS and in peripheral organs. Given that both DIPL and SD are associated with lysosomes and lipid metabolism in general, we measured the hepatic lipid profiles in rodent models of these two conditions using untargeted LC/MS to examine potential commonalities. Both model systems shared a number of perturbed lipid pathways, notably those involving metabolism of cholesteryl esters, lysophosphatidylcholines, bis(monoacylglycero)phosphates, and ceramides. We report here profound alterations in lipid metabolism in the SD liver. In addition, DIPL induced a wide range of lipid changes not previously observed in the liver, highlighting similarities with those detected in the model of SD and raising concerns that these lipid changes may be associated with underlying pathology associated with lysosomal storage disorders. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  13. Ex Vivo Drug Susceptibility Testing and Molecular Profiling of Clinical Plasmodium falciparum Isolates from Cambodia from 2008 to 2013 Suggest Emerging Piperaquine Resistance

    Science.gov (United States)

    Chaorattanakawee, Suwanna; Saunders, David L.; Sea, Darapiseth; Chanarat, Nitima; Yingyuen, Kritsanai; Sundrakes, Siratchana; Saingam, Piyaporn; Buathong, Nillawan; Sriwichai, Sabaithip; Chann, Soklyda; Se, Youry; Yom, You; Heng, Thay Kheng; Kong, Nareth; Kuntawunginn, Worachet; Tangthongchaiwiriya, Kuntida; Jacob, Christopher; Takala-Harrison, Shannon; Plowe, Christopher; Lin, Jessica T.; Chuor, Char Meng; Prom, Satharath; Tyner, Stuart D.; Gosi, Panita; Teja-Isavadharm, Paktiya; Lon, Chanthap

    2015-01-01

    Cambodia's first-line artemisinin combination therapy, dihydroartemisinin-piperaquine (DHA-PPQ), is no longer sufficiently curative against multidrug-resistant Plasmodium falciparum malaria at some Thai-Cambodian border regions. We report recent (2008 to 2013) drug resistance trends in 753 isolates from northern, western, and southern Cambodia by surveying for ex vivo drug susceptibility and molecular drug resistance markers to guide the selection of an effective alternative to DHA-PPQ. Over the last 3 study years, PPQ susceptibility declined dramatically (geomean 50% inhibitory concentration [IC50] increased from 12.8 to 29.6 nM), while mefloquine (MQ) sensitivity doubled (67.1 to 26 nM) in northern Cambodia. These changes in drug susceptibility were significantly associated with a decreased prevalence of P. falciparum multidrug resistance 1 gene (Pfmdr1) multiple copy isolates and coincided with the timing of replacing artesunate-mefloquine (AS-MQ) with DHA-PPQ as the first-line therapy. Widespread chloroquine resistance was suggested by all isolates being of the P. falciparum chloroquine resistance transporter gene CVIET haplotype. Nearly all isolates collected from the most recent years had P. falciparum kelch13 mutations, indicative of artemisinin resistance. Ex vivo bioassay measurements of antimalarial activity in plasma indicated 20% of patients recently took antimalarials, and their plasma had activity (median of 49.8 nM DHA equivalents) suggestive of substantial in vivo drug pressure. Overall, our findings suggest DHA-PPQ failures are associated with emerging PPQ resistance in a background of artemisinin resistance. The observed connection between drug policy changes and significant reduction in PPQ susceptibility with mitigation of MQ resistance supports reintroduction of AS-MQ, in conjunction with monitoring of the P. falciparum mdr1 copy number, as a stop-gap measure in areas of DHA-PPQ failure. PMID:26014942

  14. Real Time Extraction Kinetics of Electro Membrane Extraction Verified by Comparing Drug Metabolism Profiles Obtained from a Flow-Flow Electro Membrane Extraction-Mass Spectrometry System with LC-MS

    DEFF Research Database (Denmark)

    Fuchs, David; Jensen, Henrik; Pedersen-Bjergaard, Stig

    2015-01-01

    A simple to construct and operate, "dip-in" electromembrane extraction (EME) probe directly coupled to electrospray ionization-mass spectrometry (ESI-MS) for rapid extraction and real time analysis of various analytes was developed. The setup demonstrated that EME-MS can be used as a viable...... alternative to conventional protein precipitation followed by liquid chromatography-mass spectrometry (LC-MS) for studying drug metabolism. Comparison of EME-MS with LC-MS for drug metabolism analysis demonstrated for the first time that real time extraction of analytes by EME is possible. Metabolism kinetics...... were investigated for three different drugs: amitriptyline, promethazine, and methadone. By comparing the EME-MS extraction profiles of the drug substances and formed drug metabolites with the metabolism profiles obtained by conventional protein precipitation followed by LC-MS good correlation...

  15. Genetic diversity & drug sensitivity profiles of Mycobacterium tuberculosis isolates from two slums of Jaipur city, Rajasthan, India

    Directory of Open Access Journals (Sweden)

    Bharti Malhotra

    2017-01-01

    Interpretation & conclusions: About 62.7 per cent isolates from the sputum samples from slum areas were sensitive to four drugs; six per cent of isolates were MDR. Poly-resistance other than MDR was high (16%. About one-fourth isolates were clustered by either method. RAPD was rapid, less expensive but had low reproducibility. MIRU VNTR analysis could identify to greater extent the epidemiological link in the population studied.

  16. User profiles of a smartphone application to support drug adherence--experiences from the iNephro project.

    Directory of Open Access Journals (Sweden)

    Stefan Becker

    Full Text Available PURPOSE: One of the key problems in the drug therapy of patients with chronic conditions is drug adherence. In 2010 the initiative iNephro was launched (www.inephro.de. A software to support regular and correct drug intake was developed for a smartphone platform (iOS. The study investigated whether and how smartphone users deployed such an application. METHODS: Together with cooperating partners the mobile application "Medikamentenplan" ("Medication Plan" was developed. Users are able to keep and alter a list of their regular medication. A memory function supports regular intake. The application can be downloaded free of charge from the App Store™ by Apple™. After individual consent of users from December 2010 to April 2012 2042338 actions were recorded and analysed from the downloaded applications. Demographic data were collected from 2279 users with a questionnaire. RESULTS: Overall the application was used by 11688 smartphone users. 29% (3406/11688 used it at least once a week for at least four weeks. 27% (3209/11688 used the application for at least 84 days. 68% (1554/2279 of users surveyed were male, the stated age of all users was between 6-87 years (mean 44. 74% of individuals (1697 declared to be suffering from cardiovascular disease, 13% (292 had a previous history of transplantation, 9% (205 were suffering from cancer, 7% (168 reported an impaired renal function and 7% (161 suffered from diabetes mellitus. 69% (1568 of users were on <6 different medications, 9% (201 on 6 - 10 and 1% (26 on more than 10. CONCLUSION: A new smartphone application, which supports drug adherence, was used regularly by chronically ill users with a wide range of diseases over a longer period of time. The majority of users so far were middle-aged and male.

  17. Use of GeneXpert Remnants for Drug Resistance Profiling and Molecular Epidemiology of Tuberculosis in Libreville, Gabon.

    Science.gov (United States)

    Alame-Emane, Amel Kévin; Pierre-Audigier, Catherine; Aboumegone-Biyogo, Oriane Cordelia; Nzoghe-Mveang, Amandine; Cadet-Daniel, Véronique; Sola, Christophe; Djoba-Siawaya, Joël Fleury; Gicquel, Brigitte; Takiff, Howard E

    2017-07-01

    Multidrug-resistant (MDR) and extensively drug resistant (XDR) strains of Mycobacterium tuberculosis pose major problems for global health. The GeneXpert MTB/RIF (Xpert) assay rapidly detects resistance to rifampin (RIF r ), but for detection of the additional resistance that defines MDR-TB (MDR tuberculosis) and XDR-TB, and for molecular epidemiology, specimen cultures and a biosafe infrastructure are generally required. We sought to determine whether the remnants of sputa prepared for the Xpert assay could be used directly to find mutations associated with drug resistance and to study molecular epidemiology, thus providing precise characterization of MDR-TB cases in countries lacking biosafety level 3 (BSL3) facilities for M. tuberculosis cultures. After sputa were processed and run on the Xpert instrument, the leftovers of the samples prepared for the Xpert assay were used for PCR amplification and sequencing or for a line probe assay to detect mutations associated with resistance to additional drugs, as well as for molecular epidemiology with spoligotyping and selective mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing. Of 130 sputum samples from Gabon tested with the Xpert assay, 124 yielded interpretable results; 21 (17%) of these were determined to be RIF r Amplification and sequencing or a line probe assay of the Xpert remnants confirmed 18/21 samples as MDR, corresponding to 12/116 (9.5%) new and 6/8 (75%) previously treated TB patients. Spoligotyping and MIRU typing with hypervariable loci identified an MDR Beijing strain present in five samples. We conclude that the remnants of samples processed for the Xpert assay can be used in PCRs to find mutations associated with the resistance to the additional drugs that defines MDR and XDR-TB and to study molecular epidemiology without the need for culturing or a biosafe infrastructure. Copyright © 2017 Alame-Emane et al.

  18. Concentration profiles, source apportionment and risk assessment of polycyclic aromatic hydrocarbons (PAHs) in dumpsite soils from Agbogbloshie e-waste dismantling site, Accra, Ghana.

    Science.gov (United States)

    Daso, Adegbenro P; Akortia, Eric; Okonkwo, Jonathan O

    2016-06-01

    The concentrations of eighteen (18) polycyclic aromatic hydrocarbons (PAHs), including the 16 USEPA's priority PAHs as well as two alkyl-substituted naphthalenes were determined in dumpsite soils collected from different sampling sites within the Agbogbloshie e-waste dismantling site in Accra, Ghana. Following their isolation with ultrasonic-assisted extraction technique, the concentrations of the PAHs were determined by gas chromatography mass spectrometry (GC-MS). Loss-on-ignition (LOI) method was employed for the determination of total organic carbon (TOC) of the soil samples. The mean Σ18PAHs obtained were 3006, 5627, 3046, 5555, and 7199 ng g(-1) dry weight (dw) for sampling sites A (mosque), B (dismantling site), C (residential house/police station), D (personal computer repairers' shop) and E (e-waste open burning area), respectively. In all cases, the prevalence of phenanthrene, fluoranthene and pyrene was generally observed across the sampling sites. In this study, PAHs with two to three rings and four to six rings exhibited strong positive correlations, whereas BbF and BkF showed weak positive and negative correlations with other PAHs investigated. With the exception of BbF and BkF, all the PAHs had moderate to strong positive correlations with the TOC. Benzo[a]pyrene equivalent (BaPeq) concentration is a useful indicator of the carcinogenic potency of environmental matrices and these ranged between 111 and 454 ng g(-1), which are generally below the 'safe' level of 600 ng g(-1) established for the protection of the environment and human health. Interestingly, the seven carcinogenic PAHs were the major contributors to the BaPeq concentrations accounting between 97.7 and 98.3 %. Despite the minimal risk to cancer via exposure to the investigated dumpsite soil as indicated in the present study, the prolonged exposure to these pollutants via various exposure pathways may result in increased risk to cancer over time. The application of several

  19. Significance of higher drug concentration in erythrocytes of mice infected with Schistosoma japonicum and treated orally with mefloquine at single doses.

    Science.gov (United States)

    Tao, Yi; Xue, Jian; Jiang, Bin; Zhang, Hao-Bing; Xiao, Shu-Hua

    2015-12-01

    The purpose of the present study is to understand the pharmacokinetic feature of mefloquine measured by erythrocytes and plasma in Schistosoma japonicum (S. j.)-infected mice and non-infected mice after oral administration of the drug at single doses. A high-performance liquid chromatography (HPLC) method was used to measure the plasma and erythrocyte concentrations of mefloquine at varying intervals posttreatment. Our results demonstrated that in non-infected mice treated orally with mefloquine at an ineffective dose of 50 mg/kg or effective dose of 200 mg/kg for 2-72 h, the erythrocyte-to-plasma ratios of mefloquine were 5.8-11.2 or 2-14.2. On the other hand, in S. j.-infected mice treated with the same single doses of the drug, the erythrocyte and plasma drug concentration ratios were 3.1-4.6 or 2.9-8.5, manifesting that either in infected mice or in non-infected mice that received oral mefloquine resulted in higher concentration of mefloquine in erythrocytes than that in plasma. Unexpectedly, under oral administration of mefloquine at a higher single dose of 200 mg/kg, the pharmacokinetic parameter C max values for plasma from S. j.-infected and non-infected mice were 1.6 ± 0.3 and 2.0 ± 0.4 μg/mL, respectively, which were below the determined in vitro LC50 (50 % lethal concentration) value of 4.93 μg/mL. Therefore, the plasma concentration of mefloquine may display a little effect against schistosomes during the treatment. Although the values of T 1/2 and AUC0-∞ for erythrocytes were significantly longer and higher in infected mice than those of corresponding non-infect mice that received the same single mefloqine dose of 50 mg/kg, the C max value was only 2.6 ± 0.4 μg/mL lower than the determined in vitro LC50, which may explain why this low single dose is ineffective against schistosomes in vivo. After administration of higher mefloquine dose of 200 mg/kg, the C max value for erythrocytes in infected mice was 30 % (7.4 ± 0

  20. High azithromycin concentration in lungs by way of bovine serum albumin microspheres as targeted drug delivery: lung targeting efficiency in albino mice.

    Science.gov (United States)

    Ramaiah, Balakeshwa; Nagaraja, Sree Harsha; Kapanigowda, Usha Ganganahalli; Boggarapu, Prakash Rao; Subramanian, Rajarajan

    2016-05-05

    Following administration, the antibiotic travels freely through the body and also accumulates in other parts apart from the infection site. High dosage and repeated ingestion of antibiotics in the treatment of pneumonia leads to undesirable effects and inappropriate disposition of the drug. By way of targeted lung delivery, this study was intended to eliminate inappropriate azithromycin disposition and to achieve higher azithromycin concentration to treat deeper airway infections. The Azithromycin Albumin Microspheres (AAM) was prepared by emulsion polymerization technique. The optimized AAM was subjected to in vitro release study, release kinetics, XRD and stability studies. Further, in vivo pharmacokinetics and tissue distribution of azithromycin released from AAM and azithromycin solution in albino mice was investigated to prove suitability of moving forward the next steps in the clinic. The mean particle size of the optimized AAM was 10.02 μm, an optimal size to get deposited in the lungs by mechanical entrapment. The maximum encapsulation efficiency of 82.3 % was observed in this study. The release kinetic was significant and best fitted for Korsmeyer-Peppas model (R(2) = 0.9962, n = 0.41). The XRD and stability study showed favorable results. Azithromycin concentration in mice lungs (40.62 μg g(-1), 30 min) of AAM was appreciably higher than other tissues and plasma. In comparison with control, azithromycin concentration in lungs was 30.15 μg g(-1) after 30 min. The azithromycin AUC (929.94 μg h mL(-1)) and intake rate (re) (8.88) for lung were higher and statistically significant in AAM group. Compared with spleen and liver, the targeting efficacy (te) in mice lung increased by a factor of 40.15 and ~14.10 respectively. Subsequently by a factor of 8.94, the ratio of peak concentration (Ce) in lung was higher in AAM treated mice. The AAM lung tissue histopathology did not show any degenerative changes. High azithromycin concentration in

  1. 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.

  2. Assessment of metal, trace and rare earth element concentrations in a sedimentary profile from Ponte Nova reservoir, Sao Paulo state, Brazil, by NAA

    International Nuclear Information System (INIS)

    Rocha, Flavio R.; Bordon, Isabella C.C.L.; Silva, Paulo S.C.; Favaro, Deborah I.T.; Silva, Sharlleny A.; Franklin, Robson L.; Ferreira, Francisco J.

    2015-01-01

    Ponte Nova reservoir, located in the upper basin of the Tiete River in the southern region of Sao Paulo State, covers an area of 25.7 km 2 and drains an area of 320 km 2 . It was built in 1972 to control the rivers flow in the Metropolitan Region of Sao Paulo (MRSP) and water supply. A 30 cm sediment core was collected in the dam in August 2014, sliced at every 2.5 cm. Instrumental neutron activation analysis (INAA) was applied to the sediment samples to determine some major (Fe, K and Na), trace (As, Ba, Br, Co, Cr, Cs, Hf, Rb, Sb, Sc, Ta, Tb, Th, U and Zn) and rare earth (Ce, Eu, La, Lu, Nd, Sm, Tb and Yb) elements. The enrichment factor (EF) and Igeo were applied to the results by using NASC (North American Shale Composite) as reference values for sediment contamination index assessment. An EF>1.5 was obtained for As, Hf, Rb, Ta, Th, U, and rare earths Ce, Eu, La, Nd and Sm when NASC values were used, but only for Br, when the last layer concentration values were used as reference values. Similar results were obtained for the Igeo index. For semi-metal As and metals Cr and Zn concentration values were compared to oriented values from Environmental Canada (TEL and PEL) only Cr exceeded TEL value in some slices of the profile. These results may indicate that there is no anthropogenic contribution for the elements analyzed in this reservoir. Multivariate statistical analysis was applied to the results. (author)

  3. Assessment of metal, trace and rare earth element concentrations in a sedimentary profile from Ponte Nova reservoir, Sao Paulo state, Brazil, by NAA

    Energy Technology Data Exchange (ETDEWEB)

    Rocha, Flavio R.; Bordon, Isabella C.C.L.; Silva, Paulo S.C.; Favaro, Deborah I.T., E-mail: flavio@baquara.com, E-mail: defavaro@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Silva, Sharlleny A.; Franklin, Robson L.; Ferreira, Francisco J., E-mail: shasilva@sp.gov.br, E-mail: rfranklin@sp.gov.br [Companhia Ambiental do Estado de Sao Paulo (ELAI/CETESB), SP (Brazil). Setor de Quimica Inorganica

    2015-07-01

    Ponte Nova reservoir, located in the upper basin of the Tiete River in the southern region of Sao Paulo State, covers an area of 25.7 km{sup 2} and drains an area of 320 km{sup 2}. It was built in 1972 to control the rivers flow in the Metropolitan Region of Sao Paulo (MRSP) and water supply. A 30 cm sediment core was collected in the dam in August 2014, sliced at every 2.5 cm. Instrumental neutron activation analysis (INAA) was applied to the sediment samples to determine some major (Fe, K and Na), trace (As, Ba, Br, Co, Cr, Cs, Hf, Rb, Sb, Sc, Ta, Tb, Th, U and Zn) and rare earth (Ce, Eu, La, Lu, Nd, Sm, Tb and Yb) elements. The enrichment factor (EF) and Igeo were applied to the results by using NASC (North American Shale Composite) as reference values for sediment contamination index assessment. An EF>1.5 was obtained for As, Hf, Rb, Ta, Th, U, and rare earths Ce, Eu, La, Nd and Sm when NASC values were used, but only for Br, when the last layer concentration values were used as reference values. Similar results were obtained for the Igeo index. For semi-metal As and metals Cr and Zn concentration values were compared to oriented values from Environmental Canada (TEL and PEL) only Cr exceeded TEL value in some slices of the profile. These results may indicate that there is no anthropogenic contribution for the elements analyzed in this reservoir. Multivariate statistical analysis was applied to the results. (author)

  4. Recent Advances in Nanoparticle-Based Förster Resonance Energy Transfer for Biosensing, Molecular Imaging and Drug Release Profiling

    Directory of Open Access Journals (Sweden)

    Nai-Tzu Chen

    2012-12-01

    Full Text Available Förster resonance energy transfer (FRET may be regarded as a “smart” technology in the design of fluorescence probes for biological sensing and imaging. Recently, a variety of nanoparticles that include quantum dots, gold nanoparticles, polymer, mesoporous silica nanoparticles and upconversion nanoparticles have been employed to modulate FRET. Researchers have developed a number of “visible” and “activatable” FRET probes sensitive to specific changes in the biological environment that are especially attractive from the biomedical point of view. This article reviews recent progress in bringing these nanoparticle-modulated energy transfer schemes to fruition for applications in biosensing, molecular imaging and drug delivery.

  5. From Heuristic to Mathematical Modeling of Drugs Dissolution Profiles: Application of Artificial Neural Networks and Genetic Programming

    Directory of Open Access Journals (Sweden)

    Aleksander Mendyk

    2015-01-01

    Full Text Available The purpose of this work was to develop a mathematical model of the drug dissolution (Q from the solid lipid extrudates based on the empirical approach. Artificial neural networks (ANNs and genetic programming (GP tools were used. Sensitivity analysis of ANNs provided reduction of the original input vector. GP allowed creation of the mathematical equation in two major approaches: (1 direct modeling of Q versus extrudate diameter (d and the time variable (t and (2 indirect modeling through Weibull equation. ANNs provided also information about minimum achievable generalization error and the way to enhance the original dataset used for adjustment of the equations’ parameters. Two inputs were found important for the drug dissolution: d and t. The extrudates length (L was found not important. Both GP modeling approaches allowed creation of relatively simple equations with their predictive performance comparable to the ANNs (root mean squared error (RMSE from 2.19 to 2.33. The direct mode of GP modeling of Q versus d and t resulted in the most robust model. The idea of how to combine ANNs and GP in order to escape ANNs’ black-box drawback without losing their superior predictive performance was demonstrated. Open Source software was used to deliver the state-of-the-art models and modeling strategies.

  6. Survival of Listeria innocua in dry fermented sausages and changes in the typical microbiota and volatile profile as affected by the concentration of nitrate and nitrite.

    Science.gov (United States)

    Hospital, Xavier F; Hierro, Eva; Fernández, Manuela

    2012-02-15

    The involvement of nitrate and nitrite in the formation of N-nitrosamines in foods is a matter of great concern. This situation has led to revise the real amount of nitrate and nitrite needed in meat products to exert proper technological and safety activities, and also to extensive research to find alternatives to their use. The present study addresses the possibility of reducing the ingoing amounts of these additives below the legal limits established by the current European regulations. Different concentrations of nitrate and nitrite were tested on Spanish salchichón-type dry fermented sausages concerning their role in the microbiota and volatile profile. Sausages were manufactured with the maximum ingoing amounts established by the EU regulations (150 ppm NaNO(3) and 150 ppm NaNO(2)), a 25% reduction and a 50% reduction; control sausages with no nitrate/nitrite addition were also prepared. The mixtures were inoculated with 5 log cfu/g of Listeria innocua as a surrogate for Listeria monocytogenes. L. innocua numbers in the final product were approximately 1.5 log cfu/g lower in the batch with the maximum nitrate/nitrite concentration when compared to 25 and 50% reduced batches, and about 2 log cfu/g in comparison to the control sausages. The final numbers of catalase-positive cocci were 1 log cfu/g higher in the 50% nitrate/nitrite reduced batch and 2 log cfu/g higher in the control sausages, compared to products manufactured with the maximum nitrate/nitrite concentration. This increase was related to a higher amount of volatile compounds derived from carbohydrate fermentation and amino acid degradation. Sausages with no addition of nitrate/nitrite showed higher amount of volatiles from lipid oxidation. Enterobacteriaceae counts reached detectable values (1-2 log cfu/g) in both nitrate/nitrite reduced sausages and in the control batch, while these organisms were not detected in the batch with the maximum ingoing amount. Nitrate and nitrite exerted a significant

  7. Calculation of concentration profiles and their experimental verification with a pulsed sieve-plate column and the reactive material system of uranyl nitrate, nitric acid/tributyl phosphate, kerosine

    International Nuclear Information System (INIS)

    Ihle, E.

    1985-01-01

    The present study is concerned with the calculation of stationary and non-stationary concentration profiles as well as with the starting and disturbance behaviour of a pulsed sieve-plate extraction column. It investigates into the material system HNO 3 /uranyl nitrate in water with 30 per cent by volume of tributyl phosphate in kerosine. During the measurements of the concentration profiles for HNO 3 transition, which were effected in the direction of extraction and reextraction, it was shown that the concentration profiles measured in the mixer-settler range, in spite of a sixfold enlargement of the specific heat transfer area, do not differ essentially from those measured in the dispersion range. During the measurements of concentration profiles for HNO 3 /uranium transition, which were effected in the direction of coextraction and co-reextraction only for mixer-settler range, it was discovered that with increasing phase ratios, there is a depletion of the uranium concentration in the aqueous phase. If the phase ratio is further raised, it is the nitric acid, and not the uranium, that is depleted. (orig./PW) [de

  8. The risk/benefit profile of biologic drugs in real-world rheumatology practice. From ANTARES to MonitorNet

    Directory of Open Access Journals (Sweden)

    C.M. Montecucco

    2011-09-01

    Full Text Available Le principali artriti croniche ad eziopatogenesi immunoflogistica, nelle quali trovano applicazione i farmaci “biologici” (v. oltre sono la reumatoide e le sieronegative: artrite psoriasica, spondilite anchilosante, artriti reattive ed artriti “enteropatiche” (1-7. L’artrite reumatoide (AR è una malattia cronica progressiva delle articolazioni associata a significativa morbilità, deformità e riduzione della qualità di vita. La prevalenza nella popolazione, a livello mondiale, è compresa tra 0,3 ed 1%. Pur interessando in modo elettivo le articolazioni, l’AR è una malattia sistemica che può condurre a severa disabilità ed a complicanze talora fatali. La terapia farmacologica tradizionale si basa su varie combinazioni di farmaci definiti sintomatici, come gli anti-infiammatori non-steroidei (FANS, gli analgesici ed i corticosteroidi e quelli “di fondo” chiamati correntemente DMARDs (disease modifying anti-rheumatic drugs...

  9. Bacterial profile and patterns of antimicrobial drug resistance in intra-abdominal infections: Current experience in a teaching hospital

    Directory of Open Access Journals (Sweden)

    Neetu Shree

    2013-01-01

    Full Text Available Context: Bacterial isolates from intra-abdominal infections, in particular, peritonitis and their unpredictable antimicrobial resistance patterns, continue to be a matter of concern not only globally but regionally too. Aim: An attempt in the present study was made to study the patterns of drug resistance in bacterial isolates, especially gram negative bacilli in intra-abdominal infections (IAI in our hospital. Materials and Methods: From 100 cases of peritonitis, identification of isolates was done as per recommended methods. Antimicrobial susceptibility and extended-spectrum beta-lactamase (ESBL testing were performed following the CLSI guidelines. Results: A total of 133 clinical isolates were obtained, of which 108 were aerobes and 22 anaerobes. Fungal isolates were recovered in only three cases. Escherichia coli (47/108 emerged as the most predominant pathogen followed by Klebsiella spp. (27/108, while Bacteroides fragilis emerged as the predominant anaerobe (12/22. Among coliforms, 61.7% E. coli and 74.1% Klebsiella spp. were ESBL positive. A high level of resistance was observed for beta lacta