WorldWideScience

Sample records for highest drug concentration

  1. Measurement of radon concentration in dwellings in the region of highest lung cancer incidence in India

    International Nuclear Information System (INIS)

    Zoliana, B.; Rohmingliana, P.C.; Sahoo, B.K.; Mayya, Y.S.

    2015-01-01

    Monitoring of radon exhalation from soil and its concentration in indoor is found to be helpful in many investigations such as health risk assessment and others as radiation damage to bronchial cells which eventually can be the second leading cause of lung cancer next to smoking. The fact that Aizawl District, Mizoram, India has the highest lung cancer incidence rates among males and females in Age Adjusted Rate (AAR) in India as declared by Population Based Cancer Registry Report 2008 indicates the need for quantification of radon and its anomalies attached to it. Measurement of radon concentration had been carried out inside the dwellings in Aizawl district, Mizoram. A time integrated method of measurement was employed by using a solid state nuclear track detector (SSNTD) type (LR-115 films) kept in a twin cup dosimeter for measurement of concentration of radon and thoron. The dosimeters were suspended over bed rooms or living rooms in selected dwellings. They were deployed for a period of about 120 days at a time in 63 houses which were selected according to their place of location viz. fault region, places where fossil remains were found and geologically unidentified region. After the desired period of exposure, the detectors were retrieved and chemically etched which were then counted by using a spark counter. The recorded nuclear tract densities are then converted into air concentrations of Radon and Thoron

  2. Relation of average and highest solvent vapor concentrations in workplaces in small to medium enterprises and large enterprises.

    Science.gov (United States)

    Ukai, Hirohiko; Ohashi, Fumiko; Samoto, Hajime; Fukui, Yoshinari; Okamoto, Satoru; Moriguchi, Jiro; Ezaki, Takafumi; Takada, Shiro; Ikeda, Masayuki

    2006-04-01

    The present study was initiated to examine the relationship between the workplace concentrations and the estimated highest concentrations in solvent workplaces (SWPs), with special references to enterprise size and types of solvent work. Results of survey conducted in 1010 SWPs in 156 enterprises were taken as a database. Workplace air was sampled at > or = 5 crosses in each SWP following a grid sampling strategy. An additional air was grab-sampled at the site where the worker's exposure was estimated to be highest (estimated highest concentration or EHC). The samples were analyzed for 47 solvents designated by regulation, and solvent concentrations in each sample were summed up by use of additiveness formula. From the workplace concentrations at > or = 5 points, geometric mean and geometric standard deviations were calculated as the representative workplace concentration (RWC) and the indicator of variation in workplace concentration (VWC). Comparison between RWC and EHC in the total of 1010 SWPs showed that EHC was 1.2 (in large enterprises with>300 employees) to 1.7 times [in small to medium (SM) enterprises with enterprises and large enterprises, both RWC and EHC were significantly higher in SM enterprises than in large enterprises. Further comparison by types of solvent work showed that the difference was more marked in printing, surface coating and degreasing/cleaning/wiping SWPs, whereas it was less remarkable in painting SWPs and essentially nil in testing/research laboratories. In conclusion, the present observation as discussed in reference to previous publications suggests that RWC, EHC and the ratio of EHC/WRC varies substantially among different types of solvent work as well as enterprise size, and are typically higher in printing SWPs in SM enterprises.

  3. The highest global concentrations and increased abundance of oceanic plastic debris in the North Pacific: Evidence from seabirds

    Science.gov (United States)

    Robards, Martin D.; Gould, Patrick J.; Coe, James M.; Rogers, Donald B.

    1997-01-01

    Plastic pollution has risen dramatically with an increase in production of plastic resin during the past few decades. Plastic production in the United States increased from 2.9 million tons in I960 to 47.9 million tons in 1985 (Society of the Plastics Industry 1986). This has been paralleled by a significant increase in the concentration of plastic particles in oceanic surface waters of the North Pacific from the 1970s to the late 1980s (Day and Shaw 1987; Day et al. 1990a). Research during the past few decades has indicated two major interactions between marine life and oceanic plastic: entanglement and ingestion (Laist 1987). Studies in the last decade have documented the prevalence of plastic in the diets of many seabird species in the North Pacific and the need for further monitoring of those species and groups that ingest the most plastic (Day et al. 1985).

  4. Canada’s highest court unchains injection drug users; implications for harm reduction as standard of healthcare

    Directory of Open Access Journals (Sweden)

    Small Dan

    2012-07-01

    Full Text Available Abstract North America’s only supervised injection facility, Insite, opened its doors in September of 2003 with a federal exemption as a three-year scientific study. The results of the study, evaluated by an independent research team, showed it to be successful in engaging the target group in healthcare, preventing overdose death and HIV infections while increasing uptake and retention in detox and treatment. The research, published in peer-reviewed medical and scientific journals, also showed that the program did not increase public disorder, crime or drug use. Despite the substantial evidence showing the effectiveness of the program, the future of Insite came under threat with the election of a conservative federal government in 2006. As a result, the PHS Community Services Society (PHS, the non-profit organization that operates Insite, launched a legal case to protect the program. On 30 September 2011, Supreme Court of Canada ruled in favour of Insite and underscored the rights of people with addictions to the security of their person under section 7 of the Charter of Rights and Freedoms (Charter of Rights. The decision clears the ground for other jurisdictions in Canada, and perhaps North America, to implement supervised injection and harm reduction where it is epidemiologically indicated. The legal case validates the personhood of people with addictions while metaphorically unchaining them from the criminal justice system.

  5. 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

  6. Application of trajectory clustering and source attribution methods for investigating regional CO2 and CH4 concentrations at Germany's highest mountain site

    Science.gov (United States)

    Giemsa, Esther; Jacobeit, Jucundus; Ries, Ludwig; Frank, Gabriele; Hachinger, Stephan; Meyer-Arnek, Julian

    2017-04-01

    Carbon dioxide (CO2) and methane (CH4) represent the most important contributors to increased radiative forcing enhancing it together by contemporary 2.65 W/m2 on the global average (IPCC 2013). The unbroken increase of atmospheric greenhouse gases (GHG) has been unequivocally attributed to human emissions mainly coming from fossil fuel burning and land-use changes, while the oceans and terrestrial ecosystems slightly attenuate this rise with seasonally varying strength. Short-term fluctuations in the GHG concentrations that superimpose the seasonal cycle and the climate change driven trend reflect the presence of regional sources and sinks. A perfect place for investigating the comprehensive influence of these regional emissions is provided by the Environmental Research Station Schneefernerhaus (47.42°N, 10.98°E, 2.650m a.s.l.) situated in the eastern Alps at the southern side of Zugspitze mountain. Located just 300m below the highest peak of the German Alps, the exposed site is one of the currently 30 global core sites of the World Meteorological Organisation (WMO) Global Atmosphere Watch (GAW) programme and thus provides ideal conditions to study source-receptor relationships for greenhouse gases. We propose a stepwise statistical methodology for examining the relationship between synoptic-scale atmospheric transport patterns and climate gas mole fractions to finally receive a characterization of the sampling site with regard to the key processes driving CO2 and CH4 concentration levels. The first step entails a reliable radon-based filtering approach to subdivide the detected air masses according to their regional or 'background' origin. Simultaneously, a large number of ten-day back-trajectories from Schneefernerhaus every two hours over the entire study period 2011 - 2015 is calculated with the Lagrangian transport and dispersion model FLEXPART (Stohl et al. 2005) and subjected to cluster analysis. The weather- and emission strength-related (short

  7. 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) wer...

  8. Urine Creatinine Concentrations in Drug Monitoring Participants and Hospitalized Patients.

    Science.gov (United States)

    Love, Sara A; Seegmiller, Jesse C; Kloss, Julie; Apple, Fred S

    2016-10-01

    Urine drug testing is commonly performed in both clinical and forensic arenas for screening, monitoring and compliance purposes. We sought to determine if urine creatinine concentrations in monitoring program participants were significantly different from hospital in-patients and out-patients undergoing urine drug testing. We retrospectively reviewed urine creatinine submitted in June through December 2015 for all specimens undergoing urine drug testing. The 20,479 creatinine results were categorized as hospitalized patients (H) and monitoring/compliance groups for pain management (P), legal (L) or recovery (R). Median creatinine concentrations (interquartile range, mg/dL) were significantly different (P creatinine concentrations were significantly lower in the R vs. L group (Pcreatinine concentration and may indicate participants' attempts to tamper with their drug test results through dilution means. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Highest energy cosmic rays

    International Nuclear Information System (INIS)

    Nikolskij, S.

    1984-01-01

    Primary particles of cosmic radiation with highest energies cannot in view of their low intensity be recorded directly but for this purpose the phenomenon is used that these particles interact with nuclei in the atmosphere and give rise to what are known as extensive air showers. It was found that 40% of primary particles with an energy of 10 15 to 10 16 eV consist of protons, 12 to 15% of helium nuclei, 15% of iron nuclei, the rest of nuclei of other elements. Radiation intensity with an energy of 10 18 to 10 19 eV depends on the direction of incoming particles. Maximum intensity is in the direction of the centre of the nearest clustre of galaxies, minimal in the direction of the central area of our galaxy. (Ha)

  10. Highest priority in Pakistan.

    Science.gov (United States)

    Adil, E

    1968-01-01

    Responding to the challenge posed by its population problem, Pakistan's national leadership gave the highest priority to family planning in its socioeconomic development plan. In Pakistan, as elsewhere in the world, the first family planning effort originated in the private sector. The Family Planning Association of Pakistan made a tentative beginning in popularizing family planning in the country. Some clinics were opened and some publicity and education were undertaken to emphasize the need for family limitation. It was recognized soon that the government needed to assume the primarily responsibility if family planning efforts were to be successful. For the 1st plan period, 1955-60, about $10 million was allocated by the central government in the social welfare sector for voluntary family planning. The level of support continued on the same basis during the 2nd plan, 1960-65, but has been raised 4-fold in the 1965-70 scheme of family planning. Pakistan's Family Planning Association continues to play vital collaborative roles in designing and pretesting of prototype publicity material, involvement of voluntary social workers, and functional research in the clinical and public relations fields. The real breakthrough in the program came with the 3rd 5-year plan, 1965-70. High priority assigned to family planning is reflected by the total initial budget of Rs.284 million (about $60,000,000) for the 5-year period. Current policy is postulated on 6 basic assumptions: family planning efforts need to be public relations-oriented; operations should be conducted through autonomous bodies with decentralized authority at all tiers down to the grassroots level, for expeditious decision making; monetary incentives play an important role; interpersonal motivation in terms of life experience of the clientele through various contacts, coupled with mass media for publicity, can produce a sociological breakthrough; supplies and services in all related disciplines should be

  11. Highest Resolution Gaspra Mosaic

    Science.gov (United States)

    1992-01-01

    This picture of asteroid 951 Gaspra is a mosaic of two images taken by the Galileo spacecraft from a range of 5,300 kilometers (3,300 miles), some 10 minutes before closest approach on October 29, 1991. The Sun is shining from the right; phase angle is 50 degrees. The resolution, about 54 meters/pixel, is the highest for the Gaspra encounter and is about three times better than that in the view released in November 1991. Additional images of Gaspra remain stored on Galileo's tape recorder, awaiting playback in November. Gaspra is an irregular body with dimensions about 19 x 12 x 11 kilometers (12 x 7.5 x 7 miles). The portion illuminated in this view is about 18 kilometers (11 miles) from lower left to upper right. The north pole is located at upper left; Gaspra rotates counterclockwise every 7 hours. The large concavity on the lower right limb is about 6 kilometers (3.7 miles) across, the prominent crater on the terminator, center left, about 1.5 kilometers (1 mile). A striking feature of Gaspra's surface is the abundance of small craters. More than 600 craters, 100-500 meters (330-1650 feet) in diameter are visible here. The number of such small craters compared to larger ones is much greater for Gaspra than for previously studied bodies of comparable size such as the satellites of Mars. Gaspra's very irregular shape suggests that the asteroid was derived from a larger body by nearly catastrophic collisions. Consistent with such a history is the prominence of groove-like linear features, believed to be related to fractures. These linear depressions, 100-300 meters wide and tens of meters deep, are in two crossing groups with slightly different morphology, one group wider and more pitted than the other. Grooves had previously been seen only on Mars's moon Phobos, but were predicted for asteroids as well. Gaspra also shows a variety of enigmatic curved depressions and ridges in the terminator region at left. The Galileo project, whose primary mission is the

  12. Gaspra - Highest Resolution Mosaic

    Science.gov (United States)

    1992-01-01

    This picture of asteroid 951 Gaspra is a mosaic of two images taken by the Galileo spacecraft from a range of 5,300 kilometers (3,300 miles), some 10 minutes before closest approach on October 29, 1991. The Sun is shining from the right; phase angle is 50 degrees. The resolution, about 54 meters/pixel, is the highest for the Gaspra encounter and is about three times better than that in the view released in November 1991. Additional images of Gaspra remain stored on Galileo's tape recorder, awaiting playback in November. Gaspra is an irregular body with dimensions about 19 x 12 x 11 kilometers (12 x 7.5 x 7 miles). The portion illuminated in this view is about 18 kilometers (11 miles) from lower left to upper right. The north pole is located at upper left; Gaspra rotates counterclockwise every 7 hours. The large concavity on the lower right limb is about 6 kilometers (3.7 miles) across, the prominent crater on the terminator, center left, about 1.5 kilometers (1 mile). A striking feature of Gaspra's surface is the abundance of small craters. More than 600 craters, 100-500 meters (330-1650 feet) in diameter are visible here. The number of such small craters compared to larger ones is much greater for Gaspra than for previously studied bodies of comparable size such as the satellites of Mars. Gaspra's very irregular shape suggests that the asteroid was derived from a larger body by nearly catastrophic collisions. Consistent with such a history is the prominence of groove-like linear features, believed to be related to fractures. These linear depressions, 100-300 meters wide and tens of meters deep, are in two crossing groups with slightly different morphology, one group wider and more pitted than the other. Grooves had previously been seen only on Mars's moon Phobos, but were predicted for asteroids as well. Gaspra also shows a variety of enigmatic curved depressions and ridges in the terminator region at left. The Galileo project, whose primary mission is the

  13. 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.

  14. 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.

  15. Catching the Highest Energy Neutrinos

    Energy Technology Data Exchange (ETDEWEB)

    Stanev, Todor [Bartol Research Institute and Department of Physics and Astronomy, University of Delaware, Newark, DE 19716 (United States)

    2011-08-15

    We briefly discuss the possible sources of ultrahigh energy neutrinos and the methods for their detection. Then we present the results obtained by different experiments for detection of the highest energy neutrinos.

  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. Lowest cost due to highest productivity and highest quality

    Science.gov (United States)

    Wenk, Daniel

    2003-03-01

    Since global purchasing in the automotive industry has been taken up all around the world there is one main key factor that makes a TB-supplier today successful: Producing highest quality at lowest cost. The fact that Tailored Blanks, which today may reach up to 1/3 of a car body weight, are purchased on the free market but from different steel suppliers, especially in Europe and NAFTA, the philosophy on OEM side has been changing gradually towards tough evaluation criteria. "No risk at the stamping side" calls for top quality Tailored- or Tubular Blank products. Outsourcing Tailored Blanks has been starting in Japan but up to now without any quality request from the OEM side like ISO 13919-1B (welding quality standard in Europe and USA). Increased competition will automatically push the quality level and the ongoing approach to combine high strength steel with Tailored- and Tubular Blanks will ask for even more reliable system concepts which enables to weld narrow seams at highest speed. Beside producing quality, which is the key to reduce one of the most important cost driver "material scrap," in-line quality systems with true and reliable evaluation is going to be a "must" on all weld systems. Traceability of all process related data submitted to interfaces according to customer request in combination with ghost-shift-operation of TB systems are tomorrow's state-of-the-art solutions of Tailored Blank-facilities.

  18. 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

    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...

  19. Up to the highest peak!

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    In the early hours of this morning, the beam energy was ramped up to 3.5 TeV, a new world record and the highest energy for this year’s run. Now operators will prepare the machine to make high-energy collisions later this month. CERN Operations Group leader Mike Lamont (foreground) and LHC engineer in charge Alick Macpherson in the CERN Control Centre early this morning. At 5:23 this morning, Friday 19 March, the energy of both beams in the LHC was ramped up to 3.5 TeV, a new world record. During the night, operators had tested the performance of the whole machine with two so-called ‘dry runs’, that is, without beams. Given the good overall response, beams were injected at around 3:00 a.m. and stabilized soon after. The ramp started at around 4:10 and lasted about one hour. Over the last couple of weeks, operation of the LHC at 450 GeV has become routinely reproducible. The operators were able to test and optimize the beam orbit, the beam collimation, the injection and ext...

  20. 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.

  1. Plasma vs heart tissue concentration in humans - literature data analysis of drugs distribution.

    Science.gov (United States)

    Tylutki, Zofia; Polak, Sebastian

    2015-03-12

    Little is known about the uptake of drugs into the human heart, although it is of great importance nowadays, when science desires to predict tissue level behavior rather than to measure it. Although the drug concentration in cardiac tissue seems a better predictor for physiological and electrophysiological changes than its level in plasma, knowledge of this value is very limited. Tissue to plasma partition coefficients (Kp) come to rescue since they characterize the distribution of a drug among tissues as being one of the input parameters in physiologically based pharmacokinetic (PBPK) models. The article reviews cardiac surgery and forensic medical studies to provide a reference for drug concentrations in human cardiac tissue. Firstly, the focus is on whether a drug penetrates into heart tissue at a therapeutic level; the provided values refer to antibiotics, antifungals and anticancer drugs. Drugs that directly affect cardiomyocyte electrophysiology are another group of interest. Measured levels of amiodarone, digoxin, perhexiline and verapamil in different sites in human cardiac tissue where the compounds might meet ion channels, gives an insight into how these more lipophilic drugs penetrate the heart. Much data are derived from postmortem studies and they provide insight to the cardiac distribution of more than 200 drugs. The analysis depicts potential problems in defining the active concentration location, what may indirectly suggest multiple mechanisms involved in the drug distribution within the heart. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  2. The toxicological significance of post-mortem drug concentrations in bile.

    Science.gov (United States)

    Ferner, Robin E; Aronson, Jeffrey K

    2018-01-01

    Some authors have proposed that post-mortem drug concentrations in bile are useful in estimating concentrations in blood. Both The International Association of Forensic Toxicologists (TIAFT) and the US Federal Aviation Administration recommend that samples of bile should be obtained in some circumstances. Furthermore, standard toxicological texts compare blood and bile concentrations, implying that concentrations in bile are of forensic value. To review the evidence on simultaneous measurements of blood and bile drug concentrations reported in the medical literature. We made a systematic search of EMBASE 1980-2016 using the search terms ("bile/" OR "exp drug bile level/concentration/") AND "drug blood level/concentration/", PubMed 1975-2017 for ("bile[tw]" OR "biliary[tw]") AND ("concentration[tw]" OR "concentrations[tw]" OR "level[tw]" OR "levels[tw]") AND "post-mortem[tw]" and also MEDLINE 1990-2016 for information on drugs whose biliary concentrations were mentioned in standard textbooks. The search was limited to human studies without language restrictions. We also examined recent reviews, indexes of relevant journals and citations in Web of Science and Google Scholar. We calculated the bile:blood concentration ratio. The searches together yielded 1031 titles with abstracts. We scanned titles and abstracts for relevance and retrieved 230, of which 161 were considered further. We excluded 49 papers because: the paper reported only one case (30 references); the data referred only to a metabolite (1); the work was published before 1980 (3); the information concerned only samples taken during life (10); or the paper referred to a toxin or unusual recreational drug (5). The remaining 112 papers provided data for analysis, with at least two observations for each of 58 drugs. Bile:blood concentration ratios: Median bile:blood concentration ratios varied from 0.18 (range 0.058-0.32) for dextromoramide to 520 (range 0.62-43,000) for buprenorphine. Median bile

  3. Aspirin plus dipyridamole has the highest surface under the cumulative ranking curves (SUCRA) values in terms of mortality, intracranial hemorrhage, and adverse event rate among 7 drug therapies in the treatment of cerebral infarction.

    Science.gov (United States)

    Zhang, Jian-Jun; Liu, Xin

    2018-03-01

    The standardization for the clinical use of drug therapy for cerebral infarction (CI) has not yet determined in some aspects. In this paper, we discussed the efficacies of different drug therapies (aspirin, aspirin plus dipyridamole, aspirin plus clopidogrel, aspirin plus warfarin, cilostazol, warfarin, and ticlopidine) for CI. We searched databases of PubMed and Cochrane Library from the inception to April, 2017, randomized controlled trials (RCTs) met the inclusion and exclusion criteria were enrolled in this study. The network meta-analysis integrated evidences of direct and indirect comparisons to assess odd ratios (OR) and surface under the cumulative ranking curves (SUCRA) value. Thirteen eligible RCTs including 7 drug therapies were included into this network meta-analysis. The network meta-analysis results showed that CI patients who received aspirin plus dipyridamole presented lower mortality when compared with those received aspirin plus clopidogrel (OR = 0.46, 95% CI = 0.18-0.99), indicating aspirin plus dipyridamole therapy had better efficacy for CI. As for intracranial hemorrhage (ICH), stroke recurrence, and adverse event (AE) rate, there were no significant differences of efficacy among 7 drug therapies. Besides, SUCRA values demonstrated that in the 7 drug therapies, aspirin plus dipyridamole therapy was more effective than others (mortality: 80.67%; ICH: 76.6%; AE rate: 90.2%). Our findings revealed that aspirin plus dipyridamole therapy might be the optimum one for patients with CI, which could help to improve the survival of CI patients.

  4. Suspended particle and drug ingredient concentrations in hospital dispensaries and implications for pharmacists' working environments.

    Science.gov (United States)

    Inaba, Ryoichi; Hioki, Atsushi; Kondo, Yoshihiro; Nakamura, Hiroki; Nakamura, Mitsuhiro

    2016-03-01

    The aim of this study was to assess the present status of working environments for pharmacists, including the concentrations of suspended particles and suspended drug ingredients in dispensaries. We conducted a survey on the work processes and working environment in 15 hospital dispensaries, and measured the concentrations of suspended particles and suspended drug ingredients using digital dust counter and high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS), respectively. Of 25 types of powdered drugs that were frequently handled in the 15 dispensaries surveyed, 11 could be quantitatively determined. The amounts of suspended particles were relatively high, but below the reference value, in three dispensaries without dust collectors. The sedative-hypnotic drug zopiclone was detected in the suspended particles at one dispensary that was not equipped with dust collectors, and the antipyretic and analgesic drug acetaminophen was detected in two dispensaries equipped with dust collectors. There was no correlation between the daily number of prescriptions containing powdered drugs and the concentration of suspended particles in dispensaries. On the basis of the suspended particle concentrations measured, we concluded that dust collectors were effective in these dispensaries. However, suspended drug ingredients were detected also in dispensaries with dust collectors. These results suggest that the drug dust control systems of individual dispensaries should be properly installed and managed.

  5. 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.......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...

  6. Can fluconazole concentrations in saliva be used for therapeutic drug monitoring?

    NARCIS (Netherlands)

    Koks, C. H.; Crommentuyn, K. M.; Hoetelmans, R. M.; Mathôt, R. A.; Beijnen, J. H.

    2001-01-01

    The saliva/plasma concentration ratio of fluconazole was investigated in 22 HIV-1-infected individuals with an oropharyngeal Candida infection to determine whether saliva fluconazole concentrations could provide useful information for therapeutic drug monitoring in this population. Steady-state

  7. Clinical significance of 2 h plasma concentrations of first-line anti-tuberculosis drugs

    DEFF Research Database (Denmark)

    Prahl, Julie B; Johansen, Isik S; Cohen, Arieh S

    2014-01-01

    OBJECTIVES: To study 2 h plasma concentrations of the first-line tuberculosis drugs isoniazid, rifampicin, ethambutol and pyrazinamide in a cohort of patients with tuberculosis in Denmark and to determine the relationship between the concentrations and the clinical outcome. METHODS: After 6......-207 days of treatment (median 34 days) 2 h blood samples were collected from 32 patients with active tuberculosis and from three patients receiving prophylactic treatment. Plasma concentrations were determined using LC-MS/MS. Normal ranges were obtained from the literature. Clinical charts were reviewed...... failure occurred more frequently when the concentrations of isoniazid and rifampicin were both below the normal ranges (P = 0.013) and even more frequently when they were below the median 2 h drug concentrations obtained in the study (P = 0.005). CONCLUSIONS: At 2 h, plasma concentrations of isoniazid...

  8. Mathematical Model to Predict Skin Concentration after Topical Application of Drugs

    Directory of Open Access Journals (Sweden)

    Hiroaki Todo

    2013-12-01

    Full Text Available Skin permeation experiments have been broadly done since 1970s to 1980s as an evaluation method for transdermal drug delivery systems. In topically applied drug and cosmetic formulations, skin concentration of chemical compounds is more important than their skin permeations, because primary target site of the chemical compounds is skin surface or skin tissues. Furthermore, the direct pharmacological reaction of a metabolically stable drug that binds with specific receptors of known expression levels in an organ can be determined by Hill’s equation. Nevertheless, little investigation was carried out on the test method of skin concentration after topically application of chemical compounds. Recently we investigated an estimating method of skin concentration of the chemical compounds from their skin permeation profiles. In the study, we took care of “3Rs” issues for animal experiments. We have proposed an equation which was capable to estimate animal skin concentration from permeation profile through the artificial membrane (silicone membrane and animal skin. This new approach may allow the skin concentration of a drug to be predicted using Fick’s second law of diffusion. The silicone membrane was found to be useful as an alternative membrane to animal skin for predicting skin concentration of chemical compounds, because an extremely excellent extrapolation to animal skin concentration was attained by calculation using the silicone membrane permeation data. In this chapter, we aimed to establish an accurate and convenient method for predicting the concentration profiles of drugs in the skin based on the skin permeation parameters of topically active drugs derived from steady-state skin permeation experiments.

  9. An introduction to predictive modelling of drug concentration in anaesthesia monitors.

    Science.gov (United States)

    DeCou, J; Johnson, K

    2017-01-01

    A significant amount of anaesthetists' work involves the prediction of drug effects and interactions to produce a smooth general anaesthetic that minimises drug side effects and promotes rapid emergence. Successfully managing this process requires a basic understanding of drug effects, experience and inevitably some guesswork, since it is difficult (and in some cases impossible) to anticipate all relevant patient and surgical factors. Although data are generally available to allow calculation of plasma drug and effect site concentrations, this is often difficult to apply in complex clinical contexts, particularly when multiple drug types are used. In recent years, manufacturers have developed and incorporated into anaesthetic workstations technologies that use drug pharmacodynamic and pharmacokinetic data to predict drug effects and interactions. Such systems can predict the duration and effects of drugs during anaesthesia and assist the anaesthetist to understand complex drug interactions. With this information available, different drug types, doses and combinations may be tailored in a scientific way to maximise useful effects whilst minimising overdose and side-effects, particularly in high-risk patients. Examples are used to illustrate how such systems can be used in practice, and how drug effects and interactions can be simulated to "rehearse" an anaesthetic before any drugs are actually administered. At present only a small number of anaesthetic workstations use this technology, and as yet they are not able to manage all drugs used in anaesthetic practice. However, such systems have the potential to help anaesthetists manage the complexity of their work, and to provide information on predicted drug effects in a way that is useful and relevant to both experienced anaesthetists and trainees. © 2017 The Association of Anaesthetists of Great Britain and Ireland.

  10. 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.

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

    Science.gov (United States)

    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.; Vashakidze, Sergo

    2017-01-01

    ABSTRACT 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), mass-like (n = 3 patients), or consolidative (n = 1 patient). On histopathology examination, all tissue samples had necrosis; eight had a pH of ≤5.5. Tissue samples from two patients were positive for Mycobacterium tuberculosis by culture (pH 5.5 and 7.2). All 10 patients had maximal serum pyrazinamide concentrations within the recommended range of 20 to 60 μg/ml. The median lung tissue free pyrazinamide concentration was 20.96 μg/ml. The median tissue-to-serum pyrazinamide concentration ratio was 0.77 (range, 0.54 to 0.93). There was a significant inverse correlation between tissue pyrazinamide concentrations and the amounts of necrosis (R = −0.66, P = 0.04) and acid-fast bacilli (R = −0.75, P = 0.01) identified by histopathology. We found good penetration of pyrazinamide into lung tissue among patients with pulmonary tuberculosis with a variety of radiological lesion types. Our tissue pH results revealed that most lesions had a pH conducive to pyrazinamide activity. The tissue penetration of pyrazinamide highlights its importance in both drug-susceptible and drug-resistant antituberculosis treatment regimens. PMID:28373198

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

    Science.gov (United States)

    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; Vashakidze, Sergo

    2017-06-01

    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), mass-like ( n = 3 patients), or consolidative ( n = 1 patient). On histopathology examination, all tissue samples had necrosis; eight had a pH of ≤5.5. Tissue samples from two patients were positive for Mycobacterium tuberculosis by culture (pH 5.5 and 7.2). All 10 patients had maximal serum pyrazinamide concentrations within the recommended range of 20 to 60 μg/ml. The median lung tissue free pyrazinamide concentration was 20.96 μg/ml. The median tissue-to-serum pyrazinamide concentration ratio was 0.77 (range, 0.54 to 0.93). There was a significant inverse correlation between tissue pyrazinamide concentrations and the amounts of necrosis ( R = -0.66, P = 0.04) and acid-fast bacilli ( R = -0.75, P = 0.01) identified by histopathology. We found good penetration of pyrazinamide into lung tissue among patients with pulmonary tuberculosis with a variety of radiological lesion types. Our tissue pH results revealed that most lesions had a pH conducive to pyrazinamide activity. The tissue penetration of pyrazinamide highlights its importance in both drug-susceptible and drug-resistant antituberculosis treatment regimens. Copyright © 2017 American Society for Microbiology.

  13. 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

  14. An inert 3D emulsification device for individual precipitation and concentration of amorphous drug nanoparticles.

    Science.gov (United States)

    Lorenz, T; Bojko, S; Bunjes, H; Dietzel, A

    2018-02-13

    Nanosizing increases the specific surface of drug particles, leading to faster dissolution inside the organism and improving the bioavailability of poorly water-soluble drugs. A novel approach for the preparation of drug nanoparticles in water using chemically inert microfluidic emulsification devices is presented in this paper. A lithographic fabrication sequence was established, allowing fabrication of intersecting and coaxial channels of different depths in glass as is required for 3D flow-focusing. Fenofibrate was used as a model for active pharmaceutical ingredients with very low water solubility in the experiments. It was dissolved in ethyl acetate and emulsified in water, as allowed by the 3D flow-focusing geometry. In the thread formation regime, the drug solution turned into monodisperse droplets of sizes down to below 1 μm. Fast supersaturation occurs individually in each droplet, as the disperse phase solvent progressively diffuses into the surrounding water. Liquid antisolvent precipitation results in highly monodisperse and amorphous nanoparticles of sizes down to 128 nm which can be precisely controlled by the continuous and disperse phase pressure. By comparing optically measured droplet sizes with particle sizes by dynamic light scattering, we could confirm that exactly one particle forms in every droplet. Furthermore, a downstream on-chip concentration allowed withdrawal of major volumes of only the continuous phase fluid which enabled an increase of particle concentration by up to 250 times.

  15. 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.

  16. Considerations for effect site pharmacokinetics to estimate drug exposure: concentrations of antibiotics in the lung.

    Science.gov (United States)

    Rodvold, Keith A; Hope, William W; Boyd, Sara E

    2017-10-01

    Bronchoalveolar lavage (BAL) and microdialysis have become the most reliable and relevant methods for measuring lung concentrations of antibiotics, with the majority of BAL studies involving either healthy adult subjects or patients undergoing diagnostic bronchoscopy. Emphasis on the amount of drug that reaches the site of infection is increasingly recognized as necessary to determine whether a dose selection will translate to good clinical outcomes in the treatment of patients with pneumonia. Observed concentrations and/or parameters of exposure (e.g. area-under-the-curve) need to be incorporated with pharmacokinetic-pharmacodynamic indices so that rational dose selection can be identified for specific pathogens and types of pneumonic infection (community-acquired vs hospital-acquired bacterial pneumonia, including ventilator-associated bacterial pneumonia). Although having measured plasma or lung concentration-time data from critically ill patients to incorporate into pharmacokinetic-pharmacodynamic models is very unlikely during drug development, it is essential that altered distribution, augmented renal clearance, and renal or hepatic dysfunction should be considered. Notably, the number of published studies involving microdialysis and intrapulmonary penetration of antibiotics has been limited and mainly involve beta-lactam agents, levofloxacin, and fosfomycin. Opportunities to measure in high-resolution effect site spatial pharmacokinetics (e.g. with MALDI-MSI or PET imaging) and in vivo continuous drug concentrations (e.g. with aptamer-based probes) now exist. Going forward these studies could be incorporated into antibiotic development programs for pneumonia in order to further increase the probability of candidate success. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. 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.

  18. 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.

  19. Suboptimal Antituberculosis Drug Concentrations and Outcomes in Small and HIV-Coinfected Children in India: Recommendations for Dose Modifications.

    Science.gov (United States)

    Guiastrennec, Benjamin; Ramachandran, Geetha; Karlsson, Mats O; Kumar, A K Hemanth; Bhavani, Perumal Kannabiran; Gangadevi, N Poorana; Swaminathan, Soumya; Gupta, Amita; Dooley, Kelly E; Savic, Radojka M

    2017-12-16

    This work aimed to evaluate the once-daily antituberculosis treatment as recommended by the new Indian pediatric guidelines. Isoniazid, rifampin, and pyrazinamide concentration-time profiles and treatment outcome were obtained from 161 Indian children with drug-sensitive tuberculosis undergoing thrice-weekly dosing as per previous Indian pediatric guidelines. The exposure-response relationships were established using a population pharmacokinetic-pharmacodynamic approach. Rifampin exposure was identified as the unique predictor of treatment outcome. Consequently, children with low body weight (4-7 kg) and/or HIV infection, who displayed the lowest rifampin exposure, were associated with the highest probability of unfavorable treatment (therapy failure, death) outcome (P unfavorable ). Model-based simulation of optimized (P unfavorable ≤ 5%) rifampin once-daily doses were suggested per treatment weight band and HIV coinfection status (33% and 190% dose increase, respectively, from the new Indian guidelines). The established dose-exposure-response relationship could be pivotal in the development of future pediatric tuberculosis treatment guidelines. © 2017, The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  20. 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

  1. Origin of the highest energy cosmic rays

    Energy Technology Data Exchange (ETDEWEB)

    Biermann, Peter L.; Ahn, Eun-Joo; Medina-Tanco, Gustavo; Stanev, Todor

    2000-06-01

    Introducing a simple Galactic wind model patterned after the solar wind we show that back-tracing the orbits of the highest energy cosmic events suggests that they may all come from the Virgo cluster, and so probably from the active radio galaxy M87. This confirms a long standing expectation. Those powerful radio galaxies that have their relativistic jets stuck in the interstellar medium of the host galaxy, such as 3C147, will then enable us to derive limits on the production of any new kind of particle, expected in some extensions of the standard model in particle physics. New data from HIRES will be crucial in testing the model proposed here.

  2. Directional clustering in highest energy cosmic rays

    International Nuclear Information System (INIS)

    Goldberg, Haim; Weiler, Thomas J.

    2001-01-01

    An unexpected degree of small-scale clustering is observed in highest-energy cosmic ray events. Some directional clustering can be expected due to purely statistical fluctuations for sources distributed randomly in the sky. This creates a background for events originating in clustered sources. We derive analytic formulas to estimate the probability of random cluster configurations, and use these formulas to study the strong potential of the HiRes, Auger, Telescope Array and EUSO-OWL-AirWatch facilities for deciding whether any observed clustering is most likely due to nonrandom sources. For a detailed comparison to data, our analytical approach cannot compete with Monte Carlo simulations, including experimental systematics. However, our derived formulas do offer two advantages: (i) easy assessment of the significance of any observed clustering, and most importantly, (ii) an explicit dependence of cluster probabilities on the chosen angular bin size

  3. The highest energies in the Universe

    International Nuclear Information System (INIS)

    Rebel, H.

    2006-01-01

    There are not many issues of fundamental importance which have induced so many problems for astrophysicists like the question of the origin of cosmic rays. This radiation from the outer space has an energy density comparable with that of the visible starlight or of the microwave background radiation. It is an important feature of our environment with many interesting aspects. A most conspicuous feature is that the energy spectrum of cosmic rays seems to have no natural end, though resonant photopion production with the cosmic microwave background predicts a suppression of extragalactic protons above the so-called Greisen-Zatsepin-Kuz’min cutoff at about EGZK = 5 × 10"1"9 eV. In fact the highest particle energies ever observed on the Earth, stem from observations of Ultrahigh Energy Cosmic Rays (E > 3 × 10"1"9 eV). But the present observations by the AGASA and HiRes Collaborations, partly a matter of debate, are origin of a number of puzzling questions, where these particles are coming from, by which gigantic acceleration mechanism they could gain such tremendous energies and how they have been able to propagate to our Earth. These questions imply serious problems of the understanding of our Universe. There are several approaches to clarify the mysteries of the highest energies and to base the observations on larger statistical accuracy. The Pierre Auger Observatory, being in installation in the Pampa Amarilla in the Province Mendoza in Argentina, is a hybrid detector, combining a large array of water Cerenkov detectors (registering charged particles generated in giant extended air showers) with measurements of the fluorescence light produced during the air shower development. This contribution will illustrate the astrophysical motivation and the current status of the experimental efforts, and sketch the ideas about the origin of these particles.

  4. 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.

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

    DEFF Research Database (Denmark)

    Sindrup, Søren Hein; Holbech, Jakob Vormstrup; 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...... polyneuropathy were used. Treatment periods were of 4 weeks' duration, outcome was the weekly median of daily pain rated by a 0-10 numeric scale, and drug concentrations were determined by high-performance liquid chromatography. RESULTS: In 47 patients pain was reduced -1.0 (95% CI -1.5:-0.6) by imipramine, -0.......178). There was no correlation between drug concentration and pain reduction for imipramine (r= 0.17, P=0.247), whereas there was a marginally, positive correlation for pregabalin (r=0.28, P=0.057). There was no interaction between treatment and concentration classes (imipramine

  6. 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 <38.10 mg/L and rifampin peak concentration <3.01 mg/L. The relative risk of these poor outcomes below these peak concentration thresholds was 3.64 (95% confidence interval [CI], 2.28-5.83). Isoniazid had concentration-dependent antagonism with rifampin and pyrazinamide, with an adjusted odds ratio for therapy failure of 3.00 (95% CI, 2.08-4.33) in antagonism concentration range. In regard to death alone as an outcome, the same drug concentrations, plus z scores (indicators of malnutrition), and age <3 years, were highly ranked predictors. In children <3 years old, isoniazid 0- to 24-hour area under the concentration-time curve <11.95 mg/L × hour and/or rifampin peak <3.10 mg/L were the best predictors of therapy failure, with relative risk of 3.43 (95% CI, .99-11.82).  We have identified new antibiotic target concentrations, which are potential biomarkers associated with treatment failure and death in children with tuberculosis. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  7. Five year results of an international proficiency testing programme for measurement of antifungal drug concentrations

    NARCIS (Netherlands)

    Lempers, V.J.C.; Alffenaar, J.W.C.; Touw, D.J.; Burger, D.M.; Uges, D.R.A.; Aarnoutse, R.E.; Brüggemann, R.J.M.

    2014-01-01

    OBJECTIVES: Since 2007 the Dutch Association for Quality Assessment in Therapeutic Drug Monitoring (KKGT) has organized an international interlaboratory proficiency testing (PT) programme for measurement of antifungal drugs in plasma. We describe the 5 year results of the laboratories' performance.

  8. 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.

  9. Spectrophotometric Method for the Determination of Two Coformulated Drugs with Highly Different Concentrations. Application on Vildagliptin and Metformin Hydrochloride

    Science.gov (United States)

    Zaazaa, H. E.; Elzanfaly, E. S.; Soudi, A. T.; Salem, M. Y.

    2016-03-01

    A new smart simple validated spectrophotometric method was developed for the determination of two drugs one of which is in a very low concentration compared to the other. The method is based on spiking and dilution then simple mathematical manipulation of the absorbance spectra. This method was applied for the determination of a binary mixture of vildagliptin and metformin hydrochloride in the ratio 50:850 in laboratory prepared mixtures containing both drugs in this ratio and in pharmaceutical dosage form with good recoveries. The developed method was validated according to ICH guidelines and can be used for routine quality control testing.

  10. 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.

  11. 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.

  12. High affinity capture and concentration of quinacrine in polymorphonuclear neutrophils via vacuolar ATPase-mediated ion trapping: Comparison with other peripheral blood leukocytes and implications for the distribution of cationic drugs

    Energy Technology Data Exchange (ETDEWEB)

    Roy, Caroline; Gagné, Valérie; Fernandes, Maria J.G.; Marceau, François, E-mail: francois.marceau@crchul.ulaval.ca

    2013-07-15

    Many cationic drugs are concentrated in acidic cell compartments due to low retro-diffusion of the protonated molecule (ion trapping), with an ensuing vacuolar and autophagic cytopathology. In solid tissues, there is evidence that phagocytic cells, e.g., histiocytes, preferentially concentrate cationic drugs. We hypothesized that peripheral blood leukocytes could differentially take up a fluorescent model cation, quinacrine, depending on their phagocytic competence. Quinacrine transport parameters were determined in purified or total leukocyte suspensions at 37 °C. Purified polymorphonuclear leukocytes (PMNLs, essentially neutrophils) exhibited a quinacrine uptake velocity inferior to that of lymphocytes, but a consistently higher affinity (apparent K{sub M} 1.1 vs. 6.3 μM, respectively). However, the vacuolar (V)-ATPase inhibitor bafilomycin A1 prevented quinacrine transport or initiated its release in either cell type. PMNLs capture most of the quinacrine added at low concentrations to fresh peripheral blood leukocytes compared with lymphocytes and monocytes (cytofluorometry). Accumulation of the autophagy marker LC3-II occurred rapidly and at low drug concentrations in quinacrine-treated PMNLs (significant at ≥ 2.5 μM, ≥ 2 h). Lymphocytes contained more LAMP1 than PMNLs, suggesting that the mass of lysosomes and late endosomes is a determinant of quinacrine uptake V{sub max}. PMNLs, however, exhibited the highest capacity for pinocytosis (uptake of fluorescent dextran into endosomes). The selectivity of quinacrine distribution in peripheral blood leukocytes may be determined by the collaboration of a non-concentrating plasma membrane transport mechanism, tentatively identified as pinocytosis in PMNLs, with V-ATPase-mediated concentration. Intracellular reservoirs of cationic drugs are a potential source of toxicity (e.g., loss of lysosomal function in phagocytes). - Highlights: • Quinacrine is concentrated in acidic organelles via V-ATPase-mediated ion

  13. High affinity capture and concentration of quinacrine in polymorphonuclear neutrophils via vacuolar ATPase-mediated ion trapping: Comparison with other peripheral blood leukocytes and implications for the distribution of cationic drugs

    International Nuclear Information System (INIS)

    Roy, Caroline; Gagné, Valérie; Fernandes, Maria J.G.; Marceau, François

    2013-01-01

    Many cationic drugs are concentrated in acidic cell compartments due to low retro-diffusion of the protonated molecule (ion trapping), with an ensuing vacuolar and autophagic cytopathology. In solid tissues, there is evidence that phagocytic cells, e.g., histiocytes, preferentially concentrate cationic drugs. We hypothesized that peripheral blood leukocytes could differentially take up a fluorescent model cation, quinacrine, depending on their phagocytic competence. Quinacrine transport parameters were determined in purified or total leukocyte suspensions at 37 °C. Purified polymorphonuclear leukocytes (PMNLs, essentially neutrophils) exhibited a quinacrine uptake velocity inferior to that of lymphocytes, but a consistently higher affinity (apparent K M 1.1 vs. 6.3 μM, respectively). However, the vacuolar (V)-ATPase inhibitor bafilomycin A1 prevented quinacrine transport or initiated its release in either cell type. PMNLs capture most of the quinacrine added at low concentrations to fresh peripheral blood leukocytes compared with lymphocytes and monocytes (cytofluorometry). Accumulation of the autophagy marker LC3-II occurred rapidly and at low drug concentrations in quinacrine-treated PMNLs (significant at ≥ 2.5 μM, ≥ 2 h). Lymphocytes contained more LAMP1 than PMNLs, suggesting that the mass of lysosomes and late endosomes is a determinant of quinacrine uptake V max . PMNLs, however, exhibited the highest capacity for pinocytosis (uptake of fluorescent dextran into endosomes). The selectivity of quinacrine distribution in peripheral blood leukocytes may be determined by the collaboration of a non-concentrating plasma membrane transport mechanism, tentatively identified as pinocytosis in PMNLs, with V-ATPase-mediated concentration. Intracellular reservoirs of cationic drugs are a potential source of toxicity (e.g., loss of lysosomal function in phagocytes). - Highlights: • Quinacrine is concentrated in acidic organelles via V-ATPase-mediated ion trapping

  14. 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

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

    Science.gov (United States)

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

    2004-09-01

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

  16. 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

  17. Concentration and drug prices in the retail market for malaria treatment in rural Tanzania.

    Science.gov (United States)

    Goodman, Catherine; Kachur, S Patrick; Abdulla, Salim; Bloland, Peter; Mills, Anne

    2009-06-01

    The impact of market concentration has been little studied in markets for ambulatory care in the developing world, where the retail sector often accounts for a high proportion of treatments. This study begins to address this gap through an analysis of the consumer market for malaria treatment in rural areas of three districts in Tanzania. We developed methods for investigating market definition, sales volumes and concentration, and used these to explore the relationship between antimalarial retail prices and competition.The market was strongly geographically segmented and highly concentrated in terms of antimalarial sales. Antimalarial prices were positively associated with market concentration. High antimalarial prices were likely to be an important factor in the low proportion of care-seekers obtaining appropriate treatment.Retail sector distribution of subsidised antimalarials has been proposed to increase the coverage of effective treatment, but this analysis indicates that local market power may prevent such subsidies from being passed on to rural customers. Policymakers should consider the potential to maintain lower retail prices by decreasing concentration among antimalarial providers and recommending retail price levels. Copyright (c) 2009 John Wiley & Sons, Ltd.

  18. Probe for intracellular concentrations of drugs: delayed fluorescence from acridine orange

    International Nuclear Information System (INIS)

    Wardman, P.; Dennis, M.F.; White, J.

    1989-01-01

    The aim of this work is to develop fluorescent probes that will indicate effective concentrations of therapeutic agents, or endogenous protectors, at important cellular sites. Acridine orange associates with nucleic acids and emits a 'delayed' fluorescence signal. This signal is quenched by oxidants such as oxygen, nitroaryl radiosensitizers, adriamycin and mitomycin-c, and reductants such as thiols, ascorbate and other radioprotectors. The quenching of the acridine orange delayed fluorescence reflects the effective concentration of these therapeutically-important oxidants and reductants near DNA. The relative concentration of basic radiosensitizers such as pimonidazole (Ro 03-8799) near the DNA is greater than that of misonidazole. Thiols quench the delayed fluorescence signal according to the degree of ionization of the thiol function; this may model the reactivity of thiols with guanine radical sites in DNA. Ascorbate and aminopyrine do not quench the delayed fluorescence from cells stained with acridine orange as these compounds are taken up by cells very inefficiently

  19. 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

  20. 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

  1. 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

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

    DEFF Research Database (Denmark)

    Di Cagno, Massimiliano Pio; Clarelli, Fabrizio; Vabenø, Jon

    2018-01-01

    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...... 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...

  3. 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

  4. 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...

  5. Plasma drug concentrations and clinical effects of a peripheral alpha-2-adrenoceptor antagonist, MK-467, in horses sedated with detomidine.

    Science.gov (United States)

    Vainionpää, Mari H; Raekallio, Marja R; Pakkanen, Soile A E; Ranta-Panula, Ville; Rinne, Valtteri M; Scheinin, Mika; Vainio, Outi M

    2013-05-01

    To investigate plasma drug concentrations and the effect of MK-467 (L-659'066) on sedation, heart rate and gut motility in horses sedated with intravenous (IV) detomidine. Experimental randomized blinded crossover study. Six healthy horses. Detomidine (10 μg kg(-1) IV) was administered alone (DET) and in combination with MK-467 (250 μg kg(-1) IV; DET + MK). The level of sedation and intestinal sounds were scored. Heart rate (HR) and central venous pressure (CVP) were measured. Blood was collected to determine plasma drug concentrations. Repeated measures anova was used for HR, CVP and intestinal sounds, and the Student's t-test for pairwise comparisons between treatments for the area under the time-sedation curve (AUCsed ) and pharmacokinetic parameters. Significance was set at p Detomidine-induced intestinal hypomotility was prevented by MK-467. AUCsed was significantly higher with DET than DET + MK, but maximal sedations scores did not differ significantly between treatments. MK-467 lowered the AUC of the plasma concentration of detomidine, and increased its volume of distribution and clearance. MK-467 prevented detomidine induced bradycardia and intestinal hypomotility. MK-467 did not affect the clinical quality of detomidine-induced sedation, but the duration of the effect was reduced, which may have been caused by the effects of MK-467 on the plasma concentration of detomidine. MK-467 may be useful clinically in the prevention of certain peripheral side effects of detomidine in horses. © 2013 The Authors. Veterinary Anaesthesia and Analgesia © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  6. Green Pharmaceutical Analysis of Drugs Coformulated with Highly Different Concentrations Using Spiking and Manipulation of Their Ratio Spectra.

    Science.gov (United States)

    Ayoub, Bassam M

    2017-07-01

    Introducing green analysis to pharmaceutical products is considered a significant approach to preserving the environment. This method can be an environmentally friendly alternative to the existing methods, accompanied by a validated automated procedure for the analysis of a drug with the lowest possible number of samples. Different simple spectrophotometric methods were developed for the simultaneous determination of empagliflozin (EG) and metformin (MT) by manipulating their ratio spectra in their application on a recently approved pharmaceutical combination, Synjardy tablets. A spiking technique was used to increase the concentration of EG in samples prepared from the tablets to allow for the simultaneous determination of EG with MT without prior separation. Validation parameters according to International Conference on Harmonization guidelines were acceptable over a concentration range of 2-12 μg/mL for both drugs using derivative ratio and ratio subtraction coupled with extended ratio subtraction. The optimized methods were compared using one-way analysis of variance and proved to be suitable as ecofriendly approaches for industrial QC laboratories.

  7. Soybean greatly reduces valproic acid plasma concentrations: A food–drug interaction study

    Science.gov (United States)

    Marahatta, Anu; Bhandary, Bidur; Jeong, Seul-Ki; Kim, Hyung-Ryong; Chae, Han-Jung

    2014-01-01

    The aim of this study was to investigate the effects of soy on the pharmacokinetics and pharmacodynamics of valproic acid (VPA). In a preclinical study, rats were pretreated with two different amounts of soy extract for five days (150 mg/kg and 500 mg/kg), which resulted in decreases of 57% and 65% in the Cmax of VPA, respectively. AUC of VPA decreased to 83% and 70% in the soy pretreatment groups. Interestingly, the excretion rate of VPA glucuronide (VPAG) was higher in the soy-fed groups. Levels of UDP-glucuronosyltransferase (UGT) UGT1A3, UGT1A6, UGT2B7 and UGT2B15 were elevated in the soy-treated group, and GABA concentrations were elevated in the brain after VPA administration. However, this was less pronounced in soy extract pretreated group than for the untreated group. This is the first study to report the effects of soy pretreatment on the pharmacokinetics and pharmacodynamics of VPA in rodents. PMID:24618639

  8. Soybean greatly reduces valproic acid plasma concentrations: a food-drug interaction study.

    Science.gov (United States)

    Marahatta, Anu; Bhandary, Bidur; Jeong, Seul-Ki; Kim, Hyung-Ryong; Chae, Han-Jung

    2014-03-12

    The aim of this study was to investigate the effects of soy on the pharmacokinetics and pharmacodynamics of valproic acid (VPA). In a preclinical study, rats were pretreated with two different amounts of soy extract for five days (150 mg/kg and 500 mg/kg), which resulted in decreases of 57% and 65% in the Cmax of VPA, respectively. AUC of VPA decreased to 83% and 70% in the soy pretreatment groups. Interestingly, the excretion rate of VPA glucuronide (VPAG) was higher in the soy-fed groups. Levels of UDP-glucuronosyltransferase (UGT) UGT1A3, UGT1A6, UGT2B7 and UGT2B15 were elevated in the soy-treated group, and GABA concentrations were elevated in the brain after VPA administration. However, this was less pronounced in soy extract pretreated group than for the untreated group. This is the first study to report the effects of soy pretreatment on the pharmacokinetics and pharmacodynamics of VPA in rodents.

  9. 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.

  10. Doxorubicin-loaded QuadraSphere microspheres: plasma pharmacokinetics and intratumoral drug concentration in an animal model of liver cancer.

    Science.gov (United States)

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

    2010-06-01

    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.

  11. 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.

  12. Evaluation of Flexible Tacrolimus Drug Concentration Monitoring Approach in Patients Receiving Extended-Release Once-Daily Tacrolimus Tablets.

    Science.gov (United States)

    Philosophe, Benjamin; Leca, Nicolae; West-Thielke, Patricia M; Horwedel, Timothy; Culkin-Gemmell, Christine; Kistler, Kristin; Stevens, Daniel R

    2018-02-20

    The majority of United States kidney transplant patients are treated with tacrolimus, a drug effective in preventing graft rejection, but with a narrow therapeutic range, necessitating close monitoring to avoid increased risks of transplant rejection or toxicity if the tacrolimus concentration is too low or too high, respectively. The trough drug concentration tests are time sensitive; patients treated on a twice-daily basis have blood draws exactly 12 hours after their previous dose. The schedule's rigidity causes problems for both patients and health care providers. Novel once-daily tacrolimus formulations such as LCPT (an extended-release tablet by Veloxis Pharmaceuticals, Inc., Cary, North Carolina) have allowed for blood draws on a once-daily basis; however, even that schedule can be restrictive. Results from tests taken either before or after that 24-hour target time may be discarded, or worse, may lead to inappropriate dose changes. Data from ASTCOFF, a phase 3B pharmacokinetic clinical trial (NCT02339246), demonstrated that the unique pharmacokinetic curve of LCPT may allow for a therapeutic monitoring window that extends for 3 hours before or after the 24-hour monitoring target. Furthermore, important tools to help clinicians interpret these levels, such as formulas to estimate the 24-hour trough level if an alternative monitoring time is used, were constructed from these data. These study results give treating clinicians access to data that allow them to safely use and monitor LCPT in their patients and expand the body of evidence surrounding differentiation and practical application of the novel LCPT tacrolimus formulation. © 2018, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  13. Cortex Matures Faster in Youths With Highest IQ

    Science.gov (United States)

    ... NIH Cortex Matures Faster in Youths With Highest IQ Past Issues / Summer 2006 Table of Contents For ... on. Photo: Getty image (StockDisc) Youths with superior IQ are distinguished by how fast the thinking part ...

  14. Which Kids Are at Highest Risk for Suicide?

    Science.gov (United States)

    ... Share Which Kids are at Highest Risk for Suicide? Page Content Article Body No child is immune, ... who have lost a friend or relative to suicide. Studies show that a considerable number of youth ...

  15. Optimization of a model of red blood cells for the study of anti-oxidant drugs, in terms of concentration of oxidant and phosphate buffer.

    Science.gov (United States)

    Bureau, A; Lahet, J-J; Lenfant, F; Bouyer, F; Petitjean, M; Chaillot, B; Freysz, M

    2005-08-01

    The aggression of erythrocytes by an oxidative stress induces hemolysis. This paper aims to valid a model of erythrocytes in terms of composition of the phosphate buffer solution and of concentration of a well-known oxidant, AAPH. Three compositions of phosphate buffer solution are mixed with three concentrations of oxidant. The influence of these two parameters on hemolysis is independently studied by a variance analysis and a Kruskal-Wallis test when ANOVA is not available. The hemolysis rate increases with time at fixed oxidant concentration, but is not influenced by the composition of the buffer solution. The highest hemolysis rate, 90%, was only measured within 2 h with the highest oxidant concentration. If we retain this concentration of oxidant, the lower concentration of the buffer can by eliminated by a significant less hemolysis and the highest concentration of the buffer can by chosen in regard of the better precision for a similar hemolysis compared to the mean buffer. We hope to study the effect of anti-oxidant agent with such a model of erythrocytes.

  16. Identification of intestinal loss of a drug through physiologically based pharmacokinetic simulation of plasma concentration-time profiles.

    Science.gov (United States)

    Peters, Sheila Annie

    2008-01-01

    Despite recent advances in understanding of the role of the gut as a metabolizing organ, recognition of gut wall metabolism and/or other factors contributing to intestinal loss of a compound has been a challenging task due to the lack of well characterized methods to distinguish it from first-pass hepatic extraction. The implications of identifying intestinal loss of a compound in drug discovery and development can be enormous. Physiologically based pharmacokinetic (PBPK) simulations of pharmacokinetic profiles provide a simple, reliable and cost-effective way to understand the mechanisms underlying pharmacokinetic processes. The purpose of this article is to demonstrate the application of PBPK simulations in bringing to light intestinal loss of orally administered drugs, using two example compounds: verapamil and an in-house compound that is no longer in development (referred to as compound A in this article). A generic PBPK model, built in-house using MATLAB software and incorporating absorption, metabolism, distribution, biliary and renal elimination models, was employed for simulation of concentration-time profiles. Modulation of intrinsic hepatic clearance and tissue distribution parameters in the generic PBPK model was done to achieve a good fit to the observed intravenous pharmacokinetic profiles of the compounds studied. These optimized clearance and distribution parameters are expected to be invariant across different routes of administration, as long as the kinetics are linear, and were therefore employed to simulate the oral profiles of the compounds. For compounds with reasonably good solubility and permeability, an area under the concentration-time curve for the simulated oral profile that far exceeded the observed would indicate some kind of loss in the intestine. PBPK simulations applied to compound A showed substantial loss of the compound in the gastrointestinal tract in humans but not in rats. This accounted for the lower bioavailability of the

  17. 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

  18. Lung Cancer Screening May Benefit Those at Highest Risk

    Science.gov (United States)

    People at the highest risk for lung cancer, based on a risk model, may be more likely to benefit from screening with low-dose CT, a new analysis suggests. The study authors believe the findings may better define who should undergo lung cancer screening, as this Cancer Currents blog post explains.

  19. Highest weight representations of the quantum algebra Uh(gl∞)

    International Nuclear Information System (INIS)

    Palev, T.D.; Stoilova, N.I.

    1997-04-01

    A class of highest weight irreducible representations of the quantum algebra U h (gl-∞) is constructed. Within each module a basis is introduced and the transformation relations of the basis under the action of the Chevalley generators are explicitly written. (author). 16 refs

  20. Exploring the cultural dimensions of the right to the highest ...

    African Journals Online (AJOL)

    The right to enjoying the highest attainable standard of health is incorporated in many international and regional human rights instruments. This right contains both freedoms and entitlements, including the freedom to control one's own health and body and the right to an accessible system of health care, goods and services.

  1. 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-enantiome......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...

  2. Usefulness of saliva for measurement of 3,4-methylenedioxymethamphetamine and its metabolites: correlation with plasma drug concentrations and effect of salivary pH.

    Science.gov (United States)

    Navarro, M; Pichini, S; Farré, M; Ortuño, J; Roset, P N; Segura, J; de la Torre, R

    2001-10-01

    Saliva is an alternative biologic matrix for drugs-of-abuse testing that offers the advantages of noninvasive, rapid, and easy sampling. We studied the excretion profile of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolites in both saliva and plasma, as well the effect of the drug on salivary pH. Saliva and plasma samples were obtained from eight healthy MDMA consumers after ingestion of a single 100-mg dose of the drug. Concentrations of MDMA and its main metabolites, 3,4-methylenedioxyamphetamine (MDA) and 4-hydroxy-3-methoxymethamphetamine (HMMA), in saliva and plasma were measured by gas chromatography-mass spectrometry. Apparent pharmacokinetic parameters for MDMA in saliva were estimated, and the saliva-to-plasma ratio at each time interval was calculated and correlated with salivary pH. MDMA, MDA, and HMMA were detected in saliva. Salivary concentrations of MDMA were 1728.9-6510.6 microg/L and peaked at 1.5 h after drug intake. This was followed by a progressive decrease, with a mean concentration of 126.2 microg/L at 24 h. The saliva-to-plasma ratio was 32.3-1.2, with a peak of 18.1 at 1.5 h after drug administration. Salivary pH seemed to be affected by MDMA administration; pH values decreased by 0.6 units (mean pH values of 6.9 and 6.8 at 1.5 and 4 h after drug administration vs predose pH of 7.4). Measurement of MDMA in saliva is a valuable alternative to determination of plasma drug concentrations in both clinical and toxicologic studies. On-site testing is also facilitated by noninvasive and rapid collection of salivary specimens.

  3. The highest energy cosmic rays, photons and neutrinos

    International Nuclear Information System (INIS)

    Zas, Enrique

    1998-01-01

    In these lectures I introduce and discuss aspects of currently active fields of interest related to the production, transport and detection of high energy particles from extraterrestrial sources. I have payed most attention to the highest energies and I have divided the material according to the types of particles which will be searched for with different experimental facilities in planning: hadrons, gamma rays and neutrinos. Particular attention is given to shower development, stochastic acceleration and detection techniques

  4. Do optimally ripe blackberries contain the highest levels of metabolites?

    Science.gov (United States)

    Mikulic-Petkovsek, Maja; Koron, Darinka; Zorenc, Zala; Veberic, Robert

    2017-01-15

    Five blackberry cultivars were selected for the study ('Chester Thornless', 'Cacanska Bestrna', 'Loch Ness', 'Smoothstem' and 'Thornfree') and harvested at three different maturity stages (under-, optimal- and over-ripe). Optimally ripe and over-ripe blackberries contained significantly higher levels of total sugars compared to under-ripe fruit. 'Loch Ness' cultivar was characterized by 2.2-2.6-fold higher levels of total sugars than other cultivars and consequently, the highest sugar/acids ratio. 'Chester Thornless' stands out as the cultivar with the highest level of vitamin C in under-ripe (125.87mgkg(-1)) and optimally mature fruit (127.66mgkg(-1)). Maturity stage significantly affected the accumulation of phenolic compounds. The content of total anthocyanins increased for 43% at optimal maturity stage and cinnamic acid derivatives for 57% compared to under-ripe fruit. Over-ripe blackberries were distinguished by the highest content of total phenolics (1251-2115mg GAE kg(-1) FW) and greatest FRAP values (25.9-43.2mM TE kg(-1) FW). Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. 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.

  6. 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.

  7. Relation between CYP2D6 Genotype, Phenotype and Therapeutic Drug Concentrations among Nortriptyline and Venlafaxine Users in Old Age Psychiatry

    NARCIS (Netherlands)

    Berm, E; Kok, R.; Hak, E; Wilffert, B

    2016-01-01

    Objectives: To determine relations between drug concentrations and the cytochrome P450-CYP2D6 genotype or phenotype among elderly patients treated with nortriptyline or venlafaxine. Methods: A post-hoc analysis of a clinical trial was performed. Patients were grouped into phenotypes according to the

  8. The fifty highest cited papers in anterior cruciate ligament injury.

    Science.gov (United States)

    Vielgut, Ines; Dauwe, Jan; Leithner, Andreas; Holzer, Lukas A

    2017-07-01

    The anterior cruciate ligament (ACL) is one of the most common injured knee ligaments and at the same time, one of the most frequent injuries seen in the sport orthopaedic practice. Due to the clinical relevance of ACL injuries, numerous papers focussing on this topic including biomechanical-, basic science-, clinical- or animal studies, were published. The purpose of this study was to determine the most frequently cited scientific articles which address this subject, establish a ranking of the 50 highest cited papers and analyse them according to their characteristics. The 50 highest cited articles related to Anterior Cruciate Ligament Injury were searched in Thomson ISI Web of Science® by the use of defined search terms. All types of scientific papers with reference to our topic were ranked according to the absolute number of citations and analyzed for the following characteristics: journal title, year of publication, number of citations, citation density, geographic origin, article type and level of evidence. The 50 highest cited articles had up to 1624 citations. The top ten papers on this topic were cited 600 times at least. Most papers were published in the American Journal of Sports Medicine. The publication years spanned from 1941 to 2007, with the 1990s and 2000s accounting for half of the articles (n = 25). Seven countries contributed to the top 50 list, with the USA having by far the most contribution (n = 40). The majority of articles could be attributed to the category "Clinical Science & Outcome". Most of them represent a high level of evidence. Scientific articles in the field of ACL injury are highly cited. The majority of these articles are clinical studies that have a high level of evidence. Although most of the articles were published between 1990 and 2007, the highest cited articles in absolute and relative numbers were published in the early 1980s. These articles contain well established scoring- or classification systems. The

  9. A Highest Order Hypothesis Compatibility Test for Monocular SLAM

    OpenAIRE

    Edmundo Guerra; Rodrigo Munguia; Yolanda Bolea; Antoni Grau

    2013-01-01

    Simultaneous Location and Mapping (SLAM) is a key problem to solve in order to build truly autonomous mobile robots. SLAM with a unique camera, or monocular SLAM, is probably one of the most complex SLAM variants, based entirely on a bearing-only sensor working over six DOF. The monocular SLAM method developed in this work is based on the Delayed Inverse-Depth (DI-D) Feature Initialization, with the contribution of a new data association batch validation technique, the Highest Order Hyp...

  10. Robert Aymar receives one of the highest Finnish distinctions

    CERN Multimedia

    2008-01-01

    On 9 December 2008 Robert Aymar, CERN Director-General, was awarded the decoration of Commander, first class, of the Order of the Lion of Finland by the President of the Republic of Finland. This decoration, one of the highest of Finland, was presented in a ceremony by the Ambassador Hannu Himanen, Permanent Representative of Finland to the UN and other international organisations in Geneva. Robert Aymar was honoured for his service to CERN, the LHC, his role in the cooperation between Finland and CERN, as well as his contribution to science in general. In his speech the ambassador underlined CERN’s efforts in the field of education, mentioning the High school teachers programme.

  11. Comparison of direct sampling and brochoalveolar lavage for determining active drug concentrations in the pulmonary epithelial lining fluid of calves injected with enrofloxacin or tilmicosin.

    Science.gov (United States)

    Foster, D M; Sylvester, H J; Papich, M G

    2017-12-01

    Antibiotic distribution to interstitial fluid (ISF) and pulmonary epithelial fluid (PELF) was measured and compared to plasma drug concentrations in eight healthy calves. Enrofloxacin (Baytril ® 100) was administered at a dose of 12.5 mg/kg subcutaneously (SC), and tilmicosin (Micotil ® 300) was administered at a dose of 20 mg/kg SC. PELF, sampled by two different methods-bronchoalveolar lavage (BAL) and direct sampling (DS)-plasma, and ISF were collected from each calf and measured for tilmicosin, enrofloxacin and its metabolite ciprofloxacin by HPLC. Pharmacokinetic analysis was performed on the concentrations in each fluid, for each drug. The enrofloxacin/ciprofloxacin concentration as measured by AUC in DS samples was 137 ± 72% higher than in plasma, but in BAL samples, this value was 535 ± 403% (p enrofloxacin/ciprofloxacin concentrations collected by DS were significantly different than those collected by BAL, but the tilmicosin concentrations were not significantly different between the two methods. Concentrations of enrofloxacin/ciprofloxacin exceeded the MIC values for bovine respiratory disease pathogens but tilmicosin did not reach MIC levels for these pathogens in any fluids. © 2017 John Wiley & Sons Ltd.

  12. Comparison of Drug Concentrations in Human Aqueous Humor after the Administration of 0.3% Gatifloxacin Ophthalmic Gel, 0.3% Gatifloxacin and 0.5% Levofloxacin Ophthalmic Solutions.

    Science.gov (United States)

    Ding, Wenting; Ni, Weiling; Chen, Huilian; Yuan, Jingqun; Huang, Xiaodan; Zhang, Zheng; Wang, Yao; Yu, Yibo; Yao, Ke

    2015-01-01

    To investigate the penetration of 0.3% gatifloxacin ophthalmic gel, 0.3% gatifloxacin ophthalmic solution and 0.5% levofloxacin ophthalmic solution into aqueous humor after topical application. Age-related cataract patients (150 eyes in 150 cases) receiving phacoemulsification were randomly divided into three groups: a 0.3% gatifloxacin gel group (n=50), a 0.3% gatifloxacin solution group (n=50), and a 0.5% levofloxacin solution group (n=50). Each group was administered one drop of gel or solution every 15 minutes for four doses. Aqueous samples were collected at different time points after the last drop. High pressure liquid chromatography (HPLC) was applied to determine the concentrations. The one-way ANOVA analysis was performed. Our data indicated that the concentration of the gatifloxacin gel group was higher than that of the gatifloxacin solution group at all time points (P solution group at 120.0 min and 180.0 min (Psolutions reached their peak values at 60.0 min. 0.3% gatifloxacin ophthalmic gel application produced highest aqueous humor drug concentration, maintained the longest time, had the best penetration and bioavailability.

  13. Z-burst scenario for the highest energy cosmic rays

    International Nuclear Information System (INIS)

    Fodor, Z.

    2002-10-01

    The origin of highest energy cosmic rays is yet unknown. An appealing possibility is the so-called Z-burst scenario, in which a large fraction of these cosmic rays are decay products of Z bosons produced in the scattering of ultrahigh energy neutrinos on cosmological relic neutrinos. The comparison between the observed and predicted spectra constrains the mass of the heaviest neutrino. The required neutrino mass is fairly robust against variations of the presently unknown quantities, such as the amount of relic neutrino clustering, the universal photon radio background and the extragalactic magnetic field. Considering different possibilities for the ordinary cosmic rays the required neutrino masses are determined. In the most plausible case that the ordinary cosmic rays are of extragalactic origin and the universal radio background is strong enough to suppress high energy photons, the required neutrino mass is 0.08 eV ≤ m ν ≤ 0.40 eV. The required ultrahigh energy neutrino flux should be detected in the near future by experiments such as AMANDA, RICE or the Pierre Auger Observatory. (orig.)

  14. Compatibility of Firm Positioning Strategy and Website Content: Highest

    Directory of Open Access Journals (Sweden)

    Evla MUTLU KESİCİ

    2017-07-01

    Full Text Available Corporate websites are essential platforms through which firms introduce their goods and services on B2B and B2C level, express financial information for the stakeholders and share corporate values, purposes and activities. Due to its facilities, websites take part in firm positioning strategy. Accordingly this study aims to understand the innovation oriented positioning through corporate websites. The method applied in this study has been adapted from the 2QCV2Q Model developed by Mich and Franch (2000 to evaluate websites and top 30 firms with the highest Research and Development expenditures listed in Turkishtime (2015 have been analyzed. Within this context, this study presents a revised and updated method for the assessments of websites through positioning strategy framework. Findings indicate no direct relationship between website evaluation and R&D expenditure, though some common weaknesses have been put forward, such as information about management of the firms. Besides, publicly traded firms are recognized to facilitate websites more efficiently than non-publicly traded firms. Study contribute to both academia and practitioners as putting forward a new approach for 2QCV2Q Model and indicating the similarities and differences among the corporate websites through positioning perspective.

  15. Estimation of the center frequency of the highest modulation filter.

    Science.gov (United States)

    Moore, Brian C J; Füllgrabe, Christian; Sek, Aleksander

    2009-02-01

    For high-frequency sinusoidal carriers, the threshold for detecting sinusoidal amplitude modulation increases when the signal modulation frequency increases above about 120 Hz. Using the concept of a modulation filter bank, this effect might be explained by (1) a decreasing sensitivity or greater internal noise for modulation filters with center frequencies above 120 Hz; and (2) a limited span of center frequencies of the modulation filters, the top filter being tuned to about 120 Hz. The second possibility was tested by measuring modulation masking in forward masking using an 8 kHz sinusoidal carrier. The signal modulation frequency was 80, 120, or 180 Hz and the masker modulation frequencies covered a range above and below each signal frequency. Four highly trained listeners were tested. For the 80-Hz signal, the signal threshold was usually maximal when the masker frequency equaled the signal frequency. For the 180-Hz signal, the signal threshold was maximal when the masker frequency was below the signal frequency. For the 120-Hz signal, two listeners showed the former pattern, and two showed the latter pattern. The results support the idea that the highest modulation filter has a center frequency in the range 100-120 Hz.

  16. Kyle Cranmer receives the highest recognition from the US government

    CERN Multimedia

    Allen Mincer

    Kyle Cranmer with Clay Sell, Deputy Secretary of EnergyKyle Cranmer, who has worked on ATLAS as a graduate student at the University of Wisconsin-Madison, a Goldhaber Fellow at Brookhaven National Laboratory, and, most recently, an Assistant Professor at New York University, has been awarded a Presidential Early Career Award for Scientists and Engineers (PECASE). As described at the United States Department of Energy web page: "The PECASE Awards are intended to recognize some of the finest scientists and engineers who, while early in their research careers, show exceptional potential for leadership at the frontiers of scientific knowledge during the twenty-first century...The PECASE Award is the highest honor bestowed by the U.S. government on outstanding scientists and engineers beginning their independent careers." Kyle's work on ATLAS focuses on tools and strategies for data analysis, triggering, and searches for the Higgs.At the awards ceremony, which took place on Thursday Nov. 1st in Washington, D.C.,...

  17. Recreational fishing selectively captures individuals with the highest fitness potential.

    Science.gov (United States)

    Sutter, David A H; Suski, Cory D; Philipp, David P; Klefoth, Thomas; Wahl, David H; Kersten, Petra; Cooke, Steven J; Arlinghaus, Robert

    2012-12-18

    Fisheries-induced evolution and its impact on the productivity of exploited fish stocks remains a highly contested research topic in applied fish evolution and fisheries science. Although many quantitative models assume that larger, more fecund fish are preferentially removed by fishing, there is no empirical evidence describing the relationship between vulnerability to capture and individual reproductive fitness in the wild. Using males from two lines of largemouth bass (Micropterus salmoides) selectively bred over three generations for either high (HV) or low (LV) vulnerability to angling as a model system, we show that the trait "vulnerability to angling" positively correlates with aggression, intensity of parental care, and reproductive fitness. The difference in reproductive fitness between HV and LV fish was particularly evident among larger males, which are also the preferred mating partners of females. Our study constitutes experimental evidence that recreational angling selectively captures individuals with the highest potential for reproductive fitness. Our study further suggests that selective removal of the fittest individuals likely occurs in many fisheries that target species engaged in parental care. As a result, depending on the ecological context, angling-induced selection may have negative consequences for recruitment within wild populations of largemouth bass and possibly other exploited species in which behavioral patterns that determine fitness, such as aggression or parental care, also affect their vulnerability to fishing gear.

  18. Academic Training - Tevatron: studying pp collisions at the highest energy

    CERN Multimedia

    2006-01-01

    ACADEMIC TRAINING LECTURE SERIES 15, 16, 17, 18 May Main Auditorium, bldg. 500 on 15, 16, 17 May - Council Chamber on 18 May Physics at the Tevatron B. HEINEMANN, Univ. of Liverpool, FERMILAB Physics Results from the Tevatron The Tevatron proton-antiproton collider at Fermilab in the US is currently the world's highest energy collider. At the experiments CDF and D0 a broad physics programme is being pursued, ranging from flavour physics via electroweak precision measurements to searches for the Higgs boson and new particles beyond the Standard Model. In my lecture I will describe some of the highlight measurements in the flavour, electroweak and searches sectors, and the experimental techniques that are used. ENSEIGNEMENT ACADEMIQUE ACADEMIC TRAINING Françoise Benz 73127 academic.training@cern.ch If you wish to participate in one of the following courses, please tell to your supervisor and apply electronically from the course description pages that can be found on the Web at: http://www.cern.ch/...

  19. A Highest Order Hypothesis Compatibility Test for Monocular SLAM

    Directory of Open Access Journals (Sweden)

    Edmundo Guerra

    2013-08-01

    Full Text Available Simultaneous Location and Mapping (SLAM is a key problem to solve in order to build truly autonomous mobile robots. SLAM with a unique camera, or monocular SLAM, is probably one of the most complex SLAM variants, based entirely on a bearing-only sensor working over six DOF. The monocular SLAM method developed in this work is based on the Delayed Inverse-Depth (DI-D Feature Initialization, with the contribution of a new data association batch validation technique, the Highest Order Hypothesis Compatibility Test, HOHCT. The Delayed Inverse-Depth technique is used to initialize new features in the system and defines a single hypothesis for the initial depth of features with the use of a stochastic technique of triangulation. The introduced HOHCT method is based on the evaluation of statistically compatible hypotheses and a search algorithm designed to exploit the strengths of the Delayed Inverse-Depth technique to achieve good performance results. This work presents the HOHCT with a detailed formulation of the monocular DI-D SLAM problem. The performance of the proposed HOHCT is validated with experimental results, in both indoor and outdoor environments, while its costs are compared with other popular approaches.

  20. Effects of the summer holiday season on UV filter and illicit drug concentrations in the Korean wastewater system and aquatic environment.

    Science.gov (United States)

    Kim, Ki Yong; Ekpeghere, Kalu Ibe; Jeong, Hee-Jin; Oh, Jeong-Eun

    2017-08-01

    Seasonal variations in the concentrations of eight ultraviolet (UV) filters and 22 illicit drugs including their metabolites in the Korean aquatic environment were investigated. Seawater samples from three beaches, water samples from two rivers, and influents and effluents from three wastewater treatment plants were analyzed. The UV filter concentrations in the seawater, river water, and effluent samples were 39.4-296, 35.4-117, and 6.84-51.1 ng L -1 , respectively. The total UV filter concentrations in the seawater samples were 1.9-4.4 times higher at the peak of the holiday season than outside the peak holiday season. An environmental risk assessment showed that ethylhexyl methoxy cinnamate (EHMC) could cause adverse effects on aquatic organisms in the seawater at the three beaches during the holiday period. Seven of the 22 target illicit drugs including their metabolites were detected in the wastewater influent samples, and the total illicit drug concentrations in the influent samples were 0.08-65.4 ng L -1 . The estimated daily consumption rates for cis-tramadol (Cis-TRM), methamphetamine (MTP), meperidine (MEP), and codeine (COD) were 25.7-118.4, 13.8-36.1, 1.36-12.6, and 1.75-8.64 mg d -1 (1000 people) -1 , respectively. In popular vacation area, the illicit drug consumption rates (Cis-TRM, MTP and MEP) were 1.6-2.6 times higher at the peak of the summer holiday season than at the beginning of the summer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Dimethadione embryotoxicity in the rat is neither correlated with maternal systemic drug concentrations nor embryonic tissue levels

    Energy Technology Data Exchange (ETDEWEB)

    Ozolinš, Terence R.S., E-mail: ozolinst@queensu.ca [Department of Biomedical and Molecular Sciences, Program in Pharmacology and Toxicology, Queen’s University, Botterell Hall, Kingston, ON K7L 3N6 (Canada); Weston, Andrea D. [Currently at Applied Biotechnology/Lead Discovery, Bristol-Myers Squibb, 5 Research Pkwy Wallingford, CT 06492-1996 (United States); Perretta, Anthony [Currently at Pfizer Research and Development, Eastern Point Road, Groton, CT 06340 (United States); Thomson, Jason J. [Currently at Yale Stem Cell Center, Yale School of Medicine, PO Box 208073, New Haven, CT 06520-8073 (United States); Brown, Nigel A. [Division of Basic Medical Sciences, St. George’s University of London, UK SW17 0RE (United Kingdom)

    2015-11-15

    Pregnant rats treated with dimethadione (DMO), the N-demethylated metabolite of the anticonvulsant trimethadione, produce offspring having a 74% incidence of congenital heart defects (CHD); however, the incidence of CHD has high inter-litter variability (40–100%) that presents a challenge when studying the initiating events prior to the presentation of an abnormal phenotype. We hypothesized that the variability in CHD incidence was the result of differences in maternal systemic concentrations or embryonic tissue concentrations of DMO. To test this hypothesis, dams were administered 300 mg/kg DMO every 12 h from the evening of gestational day (GD) 8 until the morning of GD 11 (six total doses). Maternal serum levels of DMO were assessed on GD 11, 12, 13, 14, 15, 18 and 21. Embryonic tissue concentrations of DMO were assessed on GD 11, 12, 13 and 14. In a separate cohort of GD 12 embryos, DMO concentrations and parameters of growth and development were assessed to determine if tissue levels of DMO were correlated with these endpoints. Embryos were exposed directly to different concentrations of DMO with whole embryo culture (WEC) and their growth and development assessed. Key findings were that neither maternal systemic concentrations nor tissue concentrations of DMO identified embryos that were sensitive or resistant to DMO in vivo. Direct exposure of embryos to DMO via WEC also failed to show correlations between embryonic concentrations of DMO with developmental outcomes in vitro. We conclude that neither maternal serum nor embryonic tissue concentrations of DMO predict embryonic outcome. - Highlights: • Dimethadione (DMO) induces septation defects (VSD) in rat offspring. • Despite high rate of VSD defects inter-litter variability is 40–100%. • Maternal and embryonic concentrations of DMO were assessed. • Neither serum nor tissue levels of DMO were correlated with embryotoxicity.

  2. Dimethadione embryotoxicity in the rat is neither correlated with maternal systemic drug concentrations nor embryonic tissue levels

    International Nuclear Information System (INIS)

    Ozolinš, Terence R.S.; Weston, Andrea D.; Perretta, Anthony; Thomson, Jason J.; Brown, Nigel A.

    2015-01-01

    Pregnant rats treated with dimethadione (DMO), the N-demethylated metabolite of the anticonvulsant trimethadione, produce offspring having a 74% incidence of congenital heart defects (CHD); however, the incidence of CHD has high inter-litter variability (40–100%) that presents a challenge when studying the initiating events prior to the presentation of an abnormal phenotype. We hypothesized that the variability in CHD incidence was the result of differences in maternal systemic concentrations or embryonic tissue concentrations of DMO. To test this hypothesis, dams were administered 300 mg/kg DMO every 12 h from the evening of gestational day (GD) 8 until the morning of GD 11 (six total doses). Maternal serum levels of DMO were assessed on GD 11, 12, 13, 14, 15, 18 and 21. Embryonic tissue concentrations of DMO were assessed on GD 11, 12, 13 and 14. In a separate cohort of GD 12 embryos, DMO concentrations and parameters of growth and development were assessed to determine if tissue levels of DMO were correlated with these endpoints. Embryos were exposed directly to different concentrations of DMO with whole embryo culture (WEC) and their growth and development assessed. Key findings were that neither maternal systemic concentrations nor tissue concentrations of DMO identified embryos that were sensitive or resistant to DMO in vivo. Direct exposure of embryos to DMO via WEC also failed to show correlations between embryonic concentrations of DMO with developmental outcomes in vitro. We conclude that neither maternal serum nor embryonic tissue concentrations of DMO predict embryonic outcome. - Highlights: • Dimethadione (DMO) induces septation defects (VSD) in rat offspring. • Despite high rate of VSD defects inter-litter variability is 40–100%. • Maternal and embryonic concentrations of DMO were assessed. • Neither serum nor tissue levels of DMO were correlated with embryotoxicity.

  3. Linezolid Trough Concentrations Correlate with Mitochondrial Toxicity-Related Adverse Events in the Treatment of Chronic Extensively Drug-Resistant Tuberculosis.

    Science.gov (United States)

    Song, Taeksun; Lee, Myungsun; Jeon, Han-Seung; Park, Yumi; Dodd, Lori E; Dartois, Véronique; Follman, Dean; Wang, Jing; Cai, Ying; Goldfeder, Lisa C; Olivier, Kenneth N; Xie, Yingda; Via, Laura E; Cho, Sang Nae; Barry, Clifton E; Chen, Ray Y

    2015-11-01

    Long-term linezolid use is limited by mitochondrial toxicity-associated adverse events (AEs). Within a prospective, randomized controlled trial of linezolid to treat chronic extensively drug-resistant tuberculosis, we serially monitored the translational competence of mitochondria isolated from peripheral blood of participants by determining the cytochrome c oxidase/citrate synthase activity ratio. We compared this ratio with AEs associated with mitochondrial dysfunction. Linezolid trough concentrations were determined for 38 participants at both 600 mg and 300 mg doses. Those on 600 mg had a significantly higher risk of AE than those on 300 mg (HR 3·10, 95% CI 1·23-7 · 86). Mean mitochondrial function levels were significantly higher in patients before starting linezolid compared to their concentrations on 300 mg (P = 0·004) or 600 mg (P linezolid trough concentrations were associated with lower mitochondrial function levels (Spearman's ρ = - 0.48; P = 0.005). Mitochondrial toxicity risk increased with increasing linezolid trough concentrations, with all patients with mean linezolid trough > 2 μg/ml developing an AE related to mitochondrial toxicity, whether on 300 mg or 600 mg. Therapeutic drug monitoring may be useful to prevent the development of mitochondrial toxicity associated with long-term linezolid use.

  4. Biodegradable drug-eluting nanofiber-enveloped implants for sustained release of high bactericidal concentrations of vancomycin and ceftazidime: in vitro and in vivo studies

    Directory of Open Access Journals (Sweden)

    Hsu YH

    2014-09-01

    Full Text Available Yung-Heng Hsu,1,2 Dave Wei-Chih Chen,1 Chun-Der Tai,3 Ying-Chao Chou,1,2 Shih-Jung Liu,2 Steve Wen-Neng Ueng,1 Err-Cheng Chan4 1Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Guishan Township, 2Department of Mechanical Engineering, Chang Gung University, Guishan Township, 3Graduate Institute of Medical Mechatronics, Chang Gung University, Guishan Township, 4School of Medical Technology, Chang Gung University, Guishan Township, Taiwan Abstract: We developed biodegradable drug-eluting nanofiber-enveloped implants that provided sustained release of vancomycin and ceftazidime. To prepare the biodegradable nanofibrous membranes, poly(D,L-lactide-co-glycolide and the antibiotics were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into biodegradable drug-eluting membranes, which were then enveloped on the surface of stainless plates. An elution method and a high-performance liquid chromatography assay were employed to characterize the in vivo and in vitro release rates of the antibiotics from the nanofiber-enveloped plates. The results showed that the biodegradable nanofiber-enveloped plates released high concentrations of vancomycin and ceftazidime (well above the minimum inhibitory concentration for more than 3 and 8 weeks in vitro and in vivo, respectively. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The bioactivity ranged from 25% to 100%. In addition, the serum creatinine level remained within the normal range, suggesting that the high vancomycin concentration did not affect renal function. By adopting the electrospinning technique, we will be able to manufacture biodegradable drug-eluting implants for the long-term drug delivery of different antibiotics. Keywords: biodegradable nanofiber-enveloped plates, electrospinning, antibiotics, release characteristics

  5. 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

  6. 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

  7. Reduced antituberculosis drug concentrations in HIV-infected patients who are men or have low weight: implications for international dosing guidelines.

    Science.gov (United States)

    McIlleron, Helen; Rustomjee, Roxana; Vahedi, Mahnaz; Mthiyane, Thuli; Denti, Paolo; Connolly, Catherine; Rida, Wasima; Pym, Alexander; Smith, Peter J; Onyebujoh, Philip C

    2012-06-01

    Reduced antituberculosis drug concentrations may contribute to unfavorable treatment outcomes among HIV-infected patients with more advanced immune suppression, and few studies have evaluated pharmacokinetics of the first-line antituberculosis drugs in such patients given fixed-dose combination tablets according to international guidelines using weight bands. In this study, pharmacokinetics were evaluated in 60 patients on 4 occasions during the first month of antituberculosis therapy. Multilevel linear mixed-effects regression analysis was used to examine the effects of age, sex, weight, drug dose/kilogram, CD4(+) lymphocyte count, treatment schedule (5 versus 7 days/week), and concurrent antiretrovirals (efavirenz plus lamivudine plus zidovudine) on the area under the concentration-time curve from 0 to 12 h (AUC(0-12)) of the respective antituberculosis drugs and to compare AUC(0-12)s at day 8, day 15, and day 29 with the day 1 AUC(0-12). Median (range) age, weight, and CD4(+) lymphocyte count were 32 (18 to 47) years, 55.2 (34.4 to 98.7) kg, and 252 (12 to 500)/μl. For every 10-kg increase in body weight, the predicted day 29 AUC(0-12) increased by 14.1% (95% confidence interval [CI], 7.5, 20.8), 14.1% (95% CI, -0.7, 31.1), 6.1% (95% CI, 2.7, 9.6) and 6.0% (95% CI, 0.8, 11.3) for rifampin, isoniazid, pyrazinamide, and ethambutol, respectively. Males had day 29 AUC(0-12)s 19.3% (95% CI, 3.6, 35.1) and 14.0% (95% CI, 5.6, 22.4) lower than females for rifampin and pyrazinamide, respectively. Level of immune suppression and concomitant antiretrovirals had little effect on the concentrations of the antituberculosis agents. As they had reduced drug concentrations, it is important to review treatment responses in patients in the lower weight bands and males to inform future treatment guidelines, and revision of doses in these patients should be considered.

  8. 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

  9. Relationship between self-reported adherence, antiretroviral drug concentration measurement and self-reported symptoms in patients treated for HIV-1 infection.

    Science.gov (United States)

    Fabbiani, Massimiliano; Di Giambenedetto, Simona; Cingolani, Antonella; Fanti, Iuri; Colafigli, Manuela; Tamburrini, Enrica; Cauda, Roberto; Navarra, Pierluigi; De Luca, Andrea; Murri, Rita

    2016-01-01

    The aim of the study was to explore relationships between self-reported adherence, antiretroviral drug concentration measurement (TDM) and self-reported symptoms. We systematically administered to human immunodeficiency (HIV)-infected outpatients a questionnaire evaluating measures of self-reported adherence (missing doses during last week, deviations from the prescribed timing of therapy, self-initiated discontinuations for > 24 or 48 h, exhausting drugs and present sense of how patients are taking therapy) and a panel of referred symptoms (a symptom score was built summing self-reported scores for each listed symptom). We selected patients who completed the questionnaire and also had a TDM (mainly reflecting adherence in the past few days or weeks), thus comparing these two tools as measures of adherence. A total of 130 patients (64.6% males, median age 44 years, 76.2% with HIV RNA HIV RNA symptom score was associated with a lower self-reported adherence and with a higher proportion of undetectable drug levels. Self-reported adherence and TDM showed a correlation and seemed to be comparable tools for adherence estimation. Self-reported symptoms were associated with lower adherence and undetectable drug levels.

  10. Efavirenz Has the Highest Anti-Proliferative Effect of Non-Nucleoside Reverse Transcriptase Inhibitors against Pancreatic Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Markus Hecht

    Full Text Available Cancer prevention and therapy in HIV-1-infected patients will play an important role in future. The non-nucleoside reverse transcriptase inhibitors (NNRTI Efavirenz and Nevirapine are cytotoxic against cancer cells in vitro. As other NNRTIs have not been studied so far, all clinically used NNRTIs were tested and the in vitro toxic concentrations were compared to drug levels in patients to predict possible anti-cancer effects in vivo.Cytotoxicity was studied by Annexin-V-APC/7AAD staining and flow cytometry in the pancreatic cancer cell lines BxPC-3 and Panc-1 and confirmed by colony formation assays. The 50% effective cytotoxic concentrations (EC50 were calculated and compared to the blood levels in our patients and published data.The in vitro EC50 of the different drugs in the BxPC-3 pancreatic cancer cells were: Efavirenz 31.5 μmol/l (= 9944 ng/ml, Nevirapine 239 μmol/l (= 63,786 ng/ml, Etravirine 89.0 μmol/l (= 38,740 ng/ml, Lersivirine 543 μmol/l (= 168,523 ng/ml, Delavirdine 171 μmol/l (= 78,072 ng/ml, Rilpivirine 24.4 μmol/l (= 8941 ng/ml. As Efavirenz and Rilpivirine had the highest cytotoxic potential and Nevirapine is frequently used in HIV-1 positive patients, the results of these three drugs were further studied in Panc-1 pancreatic cancer cells and confirmed with colony formation assays. 205 patient blood levels of Efavirenz, 127 of Rilpivirine and 31 of Nevirapine were analyzed. The mean blood level of Efavirenz was 3587 ng/ml (range 162-15,363 ng/ml, of Rilpivirine 144 ng/ml (range 0-572 ng/ml and of Nevirapine 4955 ng/ml (range 1856-8697 ng/ml. Blood levels from our patients and from published data had comparable Efavirenz levels to the in vitro toxic EC50 in about 1 to 5% of all patients.All studied NNRTIs were toxic against cancer cells. A low percentage of patients taking Efavirenz reached in vitro cytotoxic blood levels. It can be speculated that in HIV-1 positive patients having high Efavirenz blood levels pancreatic

  11. 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.

  12. Application of Hill's equation for estimating area under the concentration-time curve (AUC) and use of time to AUC 90% for expressing kinetics of drug disposition.

    Science.gov (United States)

    Cheng, Hsien C

    2009-01-01

    Half life and its derived pharmacokinetic parameters are calculated on an assumption that the terminal phase of drug disposition follows a constant rate of disposition. In reality, this assumption may not necessarily be the case. A new method is needed for analyzing PK parameters if the disposition does not follow a first order PK kinetic. Cumulative area under the concentration-time curve (AUC) is plotted against time to yield a hyperbolic (or sigmoidal) AUC-time relationship curve which is then analyzed by Hill's equation to yield AUC(inf), time to achieving AUC50% (T(AUC50%)) or AUC90% (T(AUC90%)), and the Hill's slope. From these parameters, an AUC-time relationship curve can be reconstructed. Projected plasma concentration can be calculated for any time point. Time at which cumulative AUC reaches 90% (T(AUC90%)) can be used as an indicator for expressing how fast a drug is cleared. Clearance is calculated in a traditional manner (i.v. dose/AUC(inf)), and the volume of distribution is proposed to be calculated at T(AUC50%) (0.5 i.v. dose/plasma concentration at T(AUC50%)). This method of estimating AUC is applicable for both i.v. and oral data. It is concluded that the Hill's equation can be used as an alternative method for estimating AUC and analysis of PK parameters if the disposition does not follow a first order kinetic. T(AUC90%) is proposed to be used as an indicator for expressing how fast a drug is cleared from the system.

  13. 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

  14. Intraoperative radiotherapy in combination with misonidazole. In special reference to the drug concentration in tumors and normal tissues and to the initial effect of the treatment

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Masaji; Ono, Kouji; Hamanaka, Daizaburo; Dodo, Yoshihiro; Hiraoka, Masahiro [Kyoto Univ. (Japan). Faculty of Medicine

    1983-03-01

    A hypoxic cell radiosensitizer, misonidazole, was applied to 28 patients with carcinoma who received intraoperative radiotherapy. A single dose of 2-3g/m/sup 2/ of the drug was given orally to each patient three hours prior to the start of general anesthesia. The levels of misonidazole and its metabolite, desmethylmisonidazole, in blood, tumors and normal tissues taken from excised materials were measured by a high performance liquid chromatography. The results showed that the concentration levels of misonidazole and desmethylmisonidazole in blood correlated neither to oral doses of 2-3g/m/sup 2/ nor to the function of time after drug ingestion until eight hours. The mean value of blood levels was 77.1 +- 10.9..mu..g/ml. A wide range of 10-96% of the blood level was found in tumors. High levels were observed in gastric cancer and brain tumor (glioblastoma) but not in colorectal cancer and osteosarcoma. It was, however, likely that the concentrations in tumors depended on tumor sizes and/or necrotic areas rather than histologic types and/or sites of tumors. It was also noted that the concentration in normal tissues ranged widely from 11 to 87% of the blood level. Higher concentrations showing more than 75% were found in the ulnar nerve, the stomach and the skin. However, 3 of 4 materials for the stomach and 2 of 3 materials for the skin showed low levels of less than 30% and less than 22% respectively. In 27 of 28 cases different doses of 28-50 Gy with different energies of electrons were delivered intraoperatively. It is impossible so far to derive conclusive results of this study, really because of the short period of observation following the treatment.

  15. Vectorization efforts to increase Gram-negative intracellular drug concentration: a case study on HldE-K inhibitors.

    Science.gov (United States)

    Atamanyuk, Dmytro; Faivre, Fabien; Oxoby, Mayalen; Ledoussal, Benoit; Drocourt, Elodie; Moreau, François; Gerusz, Vincent

    2013-03-14

    In this paper, we present different strategies to vectorize HldE kinase inhibitors with the goal to improve their gram-negative intracellular concentration. Syntheses and biological effects of siderophoric, aminoglycosidic, amphoteric, and polycationic vectors are discussed. While siderophoric and amphoteric vectorization efforts proved to be disappointing in this series, aminoglycosidic and polycationic vectors were able for the first time to achieve synergistic effects of our inhibitors with erythromycin. Although these effects proved to be nonspecific, this study provides information about the required stereoelectronic arrangement of the polycationic amines and their basicity requirements to fulfill outer membrane destabilization resulting in better erythromycin synergies.

  16. 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

  17. The analysis of a trace amount of elements in crude drugs

    International Nuclear Information System (INIS)

    Wakayama, I.; Akagawa, J.; Yase, Y.; Yoshida, S.; Sasajima, Kazuhisa

    2001-01-01

    The concentrations and the pharmacological actions of iron and zinc in nearly 30 kinds of crude drugs of Chinese medicine are studied using the neutron activation analysis, quantitatively. The quantitative analytical results are also compared with the semi-quantitative analytical results of iron and zinc obtained by particle induced X-ray emission spectroscopy. The crude drugs with higher iron concentration were almost drugs for the mentality. The crude drugs with highest zinc concentration were also the drugs for the mentality. (H. Katsuta)

  18. Hepatitis C virus NS3 protease genotyping and drug concentration determination during triple therapy with telaprevir or boceprevir for chronic infection with genotype 1 viruses, southeastern France.

    Science.gov (United States)

    Aherfi, Sarah; Solas, Caroline; Motte, Anne; Moreau, Jacques; Borentain, Patrick; Mokhtari, Saadia; Botta-Fridlund, Danielle; Dhiver, Catherine; Portal, Isabelle; Ruiz, Jean-Marie; Ravaux, Isabelle; Bregigeon, Sylvie; Poizot-Martin, Isabelle; Stein, Andreas; Gérolami, René; Brouqui, Philippe; Tamalet, Catherine; Colson, Philippe

    2014-11-01

    Telaprevir and boceprevir, the two first hepatitis C virus (HCV) NS3 protease inhibitors (PIs), considerably increase rates of sustained virologic response in association with pegylated interferon and ribavirin in chronic HCV genotype 1 infections. The 30 first patients treated by telaprevir or boceprevir including anti-HCV therapies since 2011 in Marseille University hospitals, France, were monitored. HCV loads and plasmatic concentrations of telaprevir and boceprevir were determined on sequential blood samples. HCV NS3 protease gene population sequencing was performed at baseline of treatment and in case of treatment failure. Fifteen patients (including 7 co-infected with HIV) received telaprevir and the other 15 patients (including 4 co-infected with HIV) received boceprevir. At baseline, HCV NS3 protease from six patients harbored amino acid substitutions associated with PI-resistance. Treatment failure occurred at week 12 for 7 patients. Amino acid substitutions associated with PI-resistance were observed in six of these cases. HCV NS3 R155K and T54A/S mutants, all of genotype 1a, were found from four patients. Median (interquartile range) plasma concentrations were 3,092 ng/ml (2,320-3,525) for telaprevir and 486 ng/ml (265-619) for boceprevir. For HIV-HCV co-infected patients, median concentrations were 3,162 ng/ml (2,270-4,232) for telaprevir and 374 ng/ml (229-519) for boceprevir. Plasma drug concentration monitoring revealed undetectable concentrations for two patients at week 4, and probable non-adherence to therapy for another patient. These findings indicate that routine HCV NS3 protease sequencing and plasma PI concentration monitoring might be helpful to characterize cases of therapy failure, at a cost dramatically low compared to that of anti-HCV therapy. © 2014 Wiley Periodicals, Inc.

  19. Biochemistry of drugs. XXVII

    International Nuclear Information System (INIS)

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

    1979-01-01

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

  20. 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

  1. The Female Genital Tract Microbiome Is Associated With Vaginal Antiretroviral Drug Concentrations in Human Immunodeficiency Virus-Infected Women on Antiretroviral Therapy.

    Science.gov (United States)

    Donahue Carlson, Renee; Sheth, Anandi N; Read, Timothy D; Frisch, Michael B; Mehta, C Christina; Martin, Amy; Haaland, Richard E; Patel, Anar S; Pau, Chou-Pong; Kraft, Colleen S; Ofotokun, Igho

    2017-11-15

    The female genital tract (FGT) microbiome may affect vaginal pH and other factors that influence drug movement into the vagina. We examined the relationship between the microbiome and antiretroviral concentrations in the FGT. Over one menstrual cycle, 20 human immunodeficiency virus (HIV)-infected women virologically suppressed on tenofovir (TFV) disoproxil fumarate/emtricitabine and ritonavir-boosted atazanavir (ATV) underwent serial paired cervicovaginal and plasma sampling for antiretroviral concentrations using high-performance liquid chromatography-tandem mass spectrometry. Analysis of 16S ribosomal RNA gene sequencing of cervicovaginal lavage clustered each participant visit into a unique microbiome community type (mCT). Participants were predominantly African American (95%), with a median age of 38 years. Cervicovaginal lavage sequencing (n = 109) resulted in a low-diversity mCT dominated by Lactobacillus (n = 40), and intermediate-diversity (n = 28) and high-diversity (n = 41) mCTs with abundance of anaerobic taxa. In multivariable models, geometric mean FGT:plasma ratios varied significantly by mCT for all 3 drugs. For both ATV and TFV, FGT:plasma was significantly lower in participant visits with high- and low-diversity mCT groups (all P < .02). For emtricitabine, FGT:plasma was significantly lower in participant visits with low- vs intermediate-diversity mCT groups (P = .002). Certain FGT mCTs are associated with decreased FGT antiretroviral concentrations. These findings are relevant for optimizing antiretrovirals used for biomedical HIV prevention in women. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  2. Relationship of peak serum methotrexate concentration to prognosis and drug tolerance in non-metastatic extremity osteosarcomas.

    Science.gov (United States)

    Wang, Bo; Yao, Hao; Xie, Xianbiao; Yin, Junqiang; Zou, Changye; Huang, Gang; Shen, Jingnan

    2018-05-28

    This study aimed to explore whether peak serum methotrexate concentration (C max ) correlated with adverse events, overall survival (OS) and event-free survival (EFS) in patients with primary extremity osteosarcoma. Patients with extremity osteosarcoma who were treated at our center between 2005 and 2015 were retrospectively studied. All the patients were Enneking stage II and had received standard perioperative chemotherapy composed of high-dose methotrexate, doxorubicin, cisplatin and ifosfamide. C max and treatment-associated toxicities of each cycle were recorded. OS and EFS were estimated and compared by Kaplan-Meier survival analysis, and Cox regression models were performed for univariate comparisons. In total, 567 patients were followed for an average of 53 months (24-104 months). The estimated 3- and 5-year EFS were 71.7 and 63.1%, and the 3- and 5-year OS were 78.2 and 72.9%, respectively. C max ranged from 527 to 2495 µmol/L with a mean value of 931 ± 106 µmol/L. No significant differences in EFS and OS (p = 0.18 and p = 0.28) were observed among patients with a mean C max  > 1500, > 1000, > 700 and  1500 µmol/L had significantly increased rates of grade 3-5 toxicity. In the univariate analysis, C max was not a prognostic factor for EFS (p = 0.08) or OS (p = 0.16). C max did not correlate significantly with the oncologic prognosis of non-metastatic extremity osteosarcoma patients treated by multi-agent chemotherapy; however, C max correlated closely with toxicities and complications. The persistent inclusion of methotrexate in classical multidisciplinary chemotherapy was questioned and should be examined in future trials.

  3. 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.

  4. Applications of linking PBPK and PD models to predict the impact of genotypic variability, formulation differences, differences in target binding capacity and target site drug concentrations on drug responses and variability.

    Directory of Open Access Journals (Sweden)

    Manoranjenni eChetty

    2014-11-01

    Full Text Available This study aimed to demonstrate the added value of integrating prior in vitro data and knowledge-rich physiologically based pharmacokinetic (PBPK models with pharmacodynamics (PD models. Four distinct applications that were developed and tested are presented here. PBPK models were developed for metoprolol using different CYP2D6 genotypes based on in vitro data. Application of the models for prediction of phenotypic differences in the pharmacokinetics (PK and PD compared favourably with clinical data, demonstrating that these differences can be predicted prior to the availability of such data from clinical trials. In the second case, PK and PD data for an immediate release formulation of nifedipine together with in vitro dissolution data for a controlled release formulation (CR were used to predict the PK and PD of the CR. This approach can be useful to pharmaceutical scientists during formulation development. The operational model of agonism was used in the third application to describe the hypnotic effects of triazolam, and this was successfully extrapolated to zolpidem by changing only the drug related parameters from in vitro experiments. This PBPK modelling approach can be useful to developmental scientists who which to compare several drug candidates in the same therapeutic class. Finally, differences in QTc prolongation due to quinidine in Caucasian and Korean females were successfully predicted by the model using free heart concentrations as an input to the PD models. This PBPK linked PD model was used to demonstrate a higher sensitivity to free heart concentrations of quinidine in Caucasian females, thereby providing a mechanistic understanding of a clinical observation. In general, permutations of certain conditions which potentially change PK and hence PD may not be amenable to the conduct of clinical studies but linking PBPK with PD provides an alternative method of investigating the potential impact of PK changes on PD.

  5. Applications of linking PBPK and PD models to predict the impact of genotypic variability, formulation differences, differences in target binding capacity and target site drug concentrations on drug responses and variability.

    Science.gov (United States)

    Chetty, Manoranjenni; Rose, Rachel H; Abduljalil, Khaled; Patel, Nikunjkumar; Lu, Gaohua; Cain, Theresa; Jamei, Masoud; Rostami-Hodjegan, Amin

    2014-01-01

    This study aimed to demonstrate the added value of integrating prior in vitro data and knowledge-rich physiologically based pharmacokinetic (PBPK) models with pharmacodynamics (PDs) models. Four distinct applications that were developed and tested are presented here. PBPK models were developed for metoprolol using different CYP2D6 genotypes based on in vitro data. Application of the models for prediction of phenotypic differences in the pharmacokinetics (PKs) and PD compared favorably with clinical data, demonstrating that these differences can be predicted prior to the availability of such data from clinical trials. In the second case, PK and PD data for an immediate release formulation of nifedipine together with in vitro dissolution data for a controlled release (CR) formulation were used to predict the PK and PD of the CR. This approach can be useful to pharmaceutical scientists during formulation development. The operational model of agonism was used in the third application to describe the hypnotic effects of triazolam, and this was successfully extrapolated to zolpidem by changing only the drug related parameters from in vitro experiments. This PBPK modeling approach can be useful to developmental scientists who which to compare several drug candidates in the same therapeutic class. Finally, differences in QTc prolongation due to quinidine in Caucasian and Korean females were successfully predicted by the model using free heart concentrations as an input to the PD models. This PBPK linked PD model was used to demonstrate a higher sensitivity to free heart concentrations of quinidine in Caucasian females, thereby providing a mechanistic understanding of a clinical observation. In general, permutations of certain conditions which potentially change PK and hence PD may not be amenable to the conduct of clinical studies but linking PBPK with PD provides an alternative method of investigating the potential impact of PK changes on PD.

  6. Tenofovir alafenamide (TAF) does not deplete mitochondrial DNA in human T-cell lines at intracellular concentrations exceeding clinically relevant drug exposures.

    Science.gov (United States)

    Stray, Kirsten M; Park, Yeojin; Babusis, Darius; Callebaut, Christian; Cihlar, Tomas; Ray, Adrian S; Perron, Michel

    2017-04-01

    HIV-infected patients treated with certain nucleoside reverse transcriptase inhibitors (NRTIs) have experienced adverse effects due to drug-related mitochondrial toxicity. Tenofovir alafenamide (TAF) is a novel prodrug of the NRTI tenofovir (TFV) with an improved safety profile compared to tenofovir disoproxil fumarate (TDF). Prior in vitro studies have demonstrated that the parent nucleotide TFV has no significant effects on mtDNA synthesis. This study investigated whether clinically relevant TAF and TDF exposures affect mtDNA content in human lymphocytes. First, activated or resting peripheral blood mononuclear cells (PBMCs), as well as MT-2 and Jurkat T-cell lines, were continuously treated with ddC for 10 days to establish their susceptibility to mtDNA depletion. PBMCs had low sensitivity to NRTI-mediated mtDNA depletion in vitro. In contrast, ddC treatment of rapidly dividing MT-2 and Jurkat cells resulted in a dose-dependent decrease in mtDNA. Therefore, these two T-cell lines were selected for evaluating TAF and TDF treatment effects. MT-2 and Jurkat cells were pulse-treated with TAF or TDF every 24 h for 10 days to mimic pharmacologically relevant drug exposures. Pulse treatment of cells with 3.3 μM TAF or 1.1 μM TDF for 10 days resulted in 2- to 7-fold greater steady-state intracellular TFV-diphosphate (TFV-DP) levels than those observed clinically in TAF- or TDF-treated patients. At these concentrations, no significant TAF- (106.7% and 84.1% of control; p = 0.77 and 0.12 for MT-2 and Jurkat, respectively) or TDF- (100.6% and 91.0% of control; p = 0.91 and 0.37, respectively) associated reduction in mtDNA content was observed compared with untreated control cells. This study demonstrates that, despite delivering higher intracellular levels of TFV-DP than TDF, TAF does not inhibit mtDNA synthesis in vitro at concentrations exceeding the clinically relevant intracellular drug exposures. Thus, TAF has a low potential for mitochondrial toxicity in

  7. Matrix solid-phase dispersion on column clean-up/pre-concentration as a novel approach for fast isolation of abuse drugs from human hair.

    Science.gov (United States)

    Míguez-Framil, Martha; Moreda-Piñeiro, Antonio; Bermejo-Barrera, Pilar; Alvarez-Freire, Iván; Tabernero, María Jesús; Bermejo, Ana María

    2010-10-08

    A simple and fast sample pre-treatment method based on matrix solid-phase dispersion (MSPD) for isolating cocaine, benzoylecgonine (BZE), codeine, morphine and 6-monoacethylmorphine (6-MAM) from human hair has been developed. The MSPD approach consisted of using alumina (1.80 g) as a dispersing agent and 0.6M hydrochloric acid (4 mL) as an extracting solvent. For a fixed hair sample mass of 0.050 g, the alumina mass to sample mass ratio obtained was 36. A previously conditioned Oasis HLB cartridge (2 mL methanol, plus 2 mL ultrapure water, plus 1 mL of 0.2M/0.2M sodium hydroxide/boric acid buffer solution at pH 9.2) was attached to the end of the MSPD syringe for on column clean-up of the hydrochloric acid extract and for transferring the target compounds to a suitable solvent for gas chromatography (GC) analysis. Therefore, the adsorbed analytes were directly eluted from the Oasis HLB cartridges with 2 mL of 2% acetic acid in methanol before concentration by N(2) stream evaporation and dry extract derivatization with N-methyl-tert-butylsilyltrifluoroacetamide (BSTFA) and chlorotrimethylsilane (TMCS). The optimization/evaluation of all the factors affecting the MSPD and on column clean-up procedures has led to a fast sample treatment, and analytes extraction and pre-concentration can be finished in approximately 30 min. The developed method has been applied to eight hair samples from poli-drug abusers and measured analyte concentrations have been found to be statistically similar (95% confidence interval) to those obtained after a conventional enzymatic hydrolysis method (Pronase E). Copyright © 2010. Published by Elsevier B.V.

  8. A new application of micellar liquid chromatography in the determination of free ampicillin concentration in the drug-human serum albumin standard solution in comparison with the adsorption method.

    Science.gov (United States)

    Stępnik, Katarzyna E; Malinowska, Irena; Maciejewska, Małgorzata

    2016-06-01

    The determination of free drug concentration is a very important issue in the field of pharmacology because only the unbound drug fraction can achieve a pharmacological effect. Due to the ability to solubilize many different compounds in micellar aggregates, micellar liquid chromatography (MLC) can be used for direct determination of free drug concentration. Proteins are not retained on the stationary phase probably due to the formation of protein - surfactant complexes which are excluded from the pores of stationary phase. The micellar method is simple and fast. It does not require any pre-preparation of the tested samples for analysis. The main aim of this paper is to demonstrate a completely new applicability of the analytical use of MLC concerning the determination of free drug concentration in the standard solution of human serum albumin. The well-known adsorption method using RP-HPLC and the spectrophotometric technique was applied as the reference method. The results show that the free drug concentration value obtained in the MLC system (based on the RP-8 stationary phase and CTAB) is similar to that obtained by the adsorption method: both RP-HPLC (95.83μgmL(-1), 79.86% of free form) and spectrophotometry (95.71μgmL(-1), 79.76%). In the MLC the free drug concentration was 93.98μgmL(-1) (78.3%). This indicates that the obtained results are within the analytical range of % of free ampicillin fraction and the MLC with direct sample injection can be treated like a promising method for the determination of free drug concentration. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Concentrations of trimethoprim and sulphadoxine in tissues from goats and a cow

    International Nuclear Information System (INIS)

    Nielsen, P.; Rasmussen, F.

    1975-01-01

    The concentration of trimethoprim and sulphadoxine in plasma and tissue from goats and a cow have been determined after a single intravenous injection. Furthermore, the concentration of the two drugs and their metabolites in plasma and tissues have been determined after continuous intravenous infusion for 2 1/2 - 3 hrs. Trimethoprim was present in all tissues but brain at higher concentrations than in plasma while the concentration of sulphadoxine in the different tissues were lower than in plasma. The highest concentration of the 2 drugs and their metabolites was found in the kidney. The distribution pattern of trimethoprim and sulphadoxine was similar in cow and goats. (author)

  10. Concentrations of trimethoprim and sulphadoxine in tissues from goats and a cow

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen, P; Rasmussen, F [Kongelige Veterinaer- og Landbohoejskole, Copenhagen (Denmark)

    1975-01-01

    The concentration of trimethoprim and sulphadoxine in plasma and tissue from goats and a cow have been determined after a single intravenous injection. Furthermore, the concentration of the two drugs and their metabolites in plasma and tissues have been determined after continuous intravenous infusion for 2 1/2 - 3 hrs. Trimethoprim was present in all tissues but brain at higher concentrations than in plasma while the concentration of sulphadoxine in the different tissues were lower than in plasma. The highest concentration of the 2 drugs and their metabolites was found in the kidney. The distribution pattern of trimethoprim and sulphadoxine was similar in cow and goats.

  11. Towards a better prediction of peak concentration, volume of distribution and half-life after oral drug administration in man, using allometry.

    Science.gov (United States)

    Sinha, Vikash K; Vaarties, Karin; De Buck, Stefan S; Fenu, Luca A; Nijsen, Marjoleen; Gilissen, Ron A H J; Sanderson, Wendy; Van Uytsel, Kelly; Hoeben, Eva; Van Peer, Achiel; Mackie, Claire E; Smit, Johan W

    2011-05-01

    It is imperative that new drugs demonstrate adequate pharmacokinetic properties, allowing an optimal safety margin and convenient dosing regimens in clinical practice, which then lead to better patient compliance. Such pharmacokinetic properties include suitable peak (maximum) plasma drug concentration (C(max)), area under the plasma concentration-time curve (AUC) and a suitable half-life (t(½)). The C(max) and t(½) following oral drug administration are functions of the oral clearance (CL/F) and apparent volume of distribution during the terminal phase by the oral route (V(z)/F), each of which may be predicted and combined to estimate C(max) and t(½). Allometric scaling is a widely used methodology in the pharmaceutical industry to predict human pharmacokinetic parameters such as clearance and volume of distribution. In our previous published work, we have evaluated the use of allometry for prediction of CL/F and AUC. In this paper we describe the evaluation of different allometric scaling approaches for the prediction of C(max), V(z)/F and t(½) after oral drug administration in man. Twenty-nine compounds developed at Janssen Research and Development (a division of Janssen Pharmaceutica NV), covering a wide range of physicochemical and pharmacokinetic properties, were selected. The C(max) following oral dosing of a compound was predicted using (i) simple allometry alone; (ii) simple allometry along with correction factors such as plasma protein binding (PPB), maximum life-span potential or brain weight (reverse rule of exponents, unbound C(max) approach); and (iii) an indirect approach using allometrically predicted CL/F and V(z)/F and absorption rate constant (k(a)). The k(a) was estimated from (i) in vivo pharmacokinetic experiments in preclinical species; and (ii) predicted effective permeability in man (P(eff)), using a Caco-2 permeability assay. The V(z)/F was predicted using allometric scaling with or without PPB correction. The t(½) was estimated from

  12. 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

  13. 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

    2015-06-07

    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.

  14. 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)

    Jenkins, Mark C; Parker, Carolyn; Ritter, Donald

    2017-06-01

    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 oocyst levels and broiler performance. Litter samples were collected from a total of 15 different broiler farms encompassing a total of 45 individual houses during at least one complete grow-out cycle over a 21-mo period. Of these 15 broiler farms, three were followed for the entire 21-mo period spanning three ACD and four VAC cycles. Samples were collected at 2, 4, and 7-8 wk of grow-out corresponding to starter, grower, and withdraw periods of the ACD cycle. On a number of occasions, litter samples were obtained just prior to chick placement. Eimeria oocysts were isolated from all samples, counted by microscopy, and extracted for DNA to identify Eimeria species by ITS1 PCR. In general, Eimeria oocyst concentration in litter reached peak levels at 2-4 wk of grow-out regardless of coccidiosis control measure being used. However, peak oocyst numbers were sometimes delayed until 7-8 wk, indicating some level of Eimeria spp. drug resistance or incomplete vaccine coverage. Eimeria maxima , Eimeria acervulina , Eimeria praecox, and Eimeria tenella were generally present in all samples, and no difference in the species composition was noted between houses on a particular farm. While Eimeria species composition was similar among houses, Eimeria spp. oocyst levels exhibited sporadic peaks in one house of a given location's houses. Of particular interest was the observed correlation between E. maxima oocyst abundance and chick mortality. However, no correlation was observed in E. maxima oocyst levels, and the performance parameters adjusted feed conversion ratio and average daily weight gain. This study showed that understanding the dynamics of Eimeria spp. oocyst levels and species

  15. Cytogenetic and oxidative status of human lymphocytes after exposure to clinically relevant concentrations of antimalarial drugs atovaquone and proguanil hydrochloride in vitro.

    Science.gov (United States)

    Dinter, Domagoj; Gajski, Goran; Domijan, Ana-Marija; Garaj-Vrhovac, Vera

    2015-12-01

    Atovaquone (ATO) and proguanil hydrochloride (PROG) is the fixed combination for the prevention and treatment of Plasmodium falciparum malaria. As safe and effective antimalarial drugs are needed in both the treatment and the prophylaxis of malaria, this study was performed to investigate their possible cyto/genotoxic potential towards human lymphocytes and the possible mechanism responsible for it. Two different concentrations of ATO and PROG were used with and without S9 metabolic activation. The concentrations used were those found in human plasma when a fixed-dose combination of ATO and PROG was used: 2950/130 ng/mL after prophylactic treatment and 11 800/520 ng/mL after treatment of malaria, respectively. Possible cellular and DNA-damaging effects were evaluated by cell viability and alkaline comet assays, while oxidative stress potential was evaluated by formamidopyrimidine-DNA glycosylase (Fpg)-modified comet assay, in addition to measuring malondialdehyde and glutathione levels. According to our results, the ATO/PROG combination displayed only weak cyto/genotoxic potential towards human lymphocytes with no impact on oxidative stress parameters, suggesting that oxidative stress is not implicated in their mechanism of action towards human lymphocytes. Given that the key portion of the damaging effects was induced after S9 metabolic activation, it is to presume that the principal metabolite of PROG, cycloguanil, had the greatest impact. The obtained results indicate that the ATO/PROG combination is relatively safe for the consumption from the aspect of cyto/genotoxicity, especially if used for prophylactic treatment. Nevertheless, further cytogenetic research and regular patient monitoring are needed to minimize the risk of adverse events especially among frequent travellers. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  16. [PK/PD breakpoints and clinical/bacteriological effects of cefcapene pivoxil fine granules for children at free drug concentrations in pediatric patients with respiratory infection].

    Science.gov (United States)

    Toyonaga, Yoshikiyo; Iwai, Naoichi; Motohiro, Takashi; Sunakawa, Keisuke; Fujii, Ryochi

    2008-06-01

    A post-marketing clinical study was previously conducted in pediatric patients with respiratory infection to evaluate the pharmacokinetics, efficacy and safety of cefcapene pivoxil (CFPN-PI) fine granules for children. Based on the results from this study, we evaluated PK/PD breakpoints and clinical/bacteriological effects of CFPN-PI at free drug concentrations in pediatric patients with respiratory infection to determine an effective and safe dosage regimen of CFPN-PI. The following results were obtained from 61 pediatric patients evaluated in our research. 1) The response rate of pediatric respiratory infection to CFPN-PI was 100% for laryngopharyngitis, 84.6% for acute bronchitis, 100% for tonsillitis, 100% for pneumonia and 95.8% for all. 2) The bacteriological response (eradication rate of Haemophilus influenzae, Streptococcus pyogenes, Moraxella catarrhalis, Streptococcus pneumoniae, etc.) of pediatric respiratory infection to CFPN-PI was 87.5% for laryngopharyngitis, 66.7% for acute bronchitis, 75.0% for tonsillitis, 63.6% for pneumonia and 73.8% for all. 3) The blood concentration simulation demonstrated that the PK/PD breakpoint exceeding the time above MIC (TAM) of 40% after administration of CFPN-PI 3 mg/kg three times daily was 0.27 microg/mL. 4) The pediatric patients with respiratory infection were stratified by the TAM (%) of CFPN-PI into 40% to 100% (TAM > or = 40% group) and 0% to 40% (TAM or = 40% group, and 88.9% and 62.5% in the TAM or = 40% group than in the TAM < 40% group, although the between-group difference was not statistically significant.

  17. Competing pathways in drug metabolism. I. Effect of input concentration on the conjugation of gentisamide in the once-through in situ perfused rat liver preparation

    International Nuclear Information System (INIS)

    Morris, M.E.; Yuen, V.; Tang, B.K.; Pang, K.S.

    1988-01-01

    Sulfation and glucuronidation are two parallel pathways for the metabolism of phenolic substrates. Gentisamide (GAM) was used as a model compound to examine the effects of parallel competing pathways on drug disappearance and metabolite formation in the once-through perfused rat liver preparation. GAM was found to form one glucuronide (GAM-5G) and two sulfate (GAM-2S and GAM-5S) conjugates. These GAM conjugates were biosynthesized in recirculating rat liver preparations, and were isolated by preparative high-performance liquid chromatography. Specific incorporation of 35S-sodium sulfate and [14C]glucose into GAM sulfate and glucuronide conjugates revealed corresponding elution patterns as labeled GAM metabolites. Their identities were characterized by enzymatic and acid hydrolyses and by NMR spectroscopy. Gentisamide-5-sulfate (GAM-5S) and gentisamide-5-glucuronide (GAM-5G) are major metabolites, and gentisamide-2-sulfate (GAM-2S) is a minor metabolite. Single-pass rat liver perfusions were used to examine the effect of stepwise increases/decreases of input GAM concentration (CIn) on the extraction ratio (E) of GAM and formation of metabolites. The E of GAM remained constant (about 0.89) at input concentrations from 0.9 to 120 microM and decreased at CIn greater than 120 microM. Metabolite patterns, however, changed with GAM CIn, even when E was constant at CIn up to 120 microM. GAM-5S was present as the major metabolite of GAM at all GAM CInS in most liver preparations but the proportions of GAM-5S and GAM-2S decreased at increasing CIn; the proportion of GAM-5G, a minor metabolite at low CIn, increased with increasing CIn. Biliary excretion rates at steady state accounted for 5.3 +/- 2.7% (mean +/- S.D.) of the input rate: GAM-5G was the predominant metabolite found

  18. Effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory drugs on the production of reactive oxygen species by activated rat neutrophils

    Directory of Open Access Journals (Sweden)

    Paino I.M.M.

    2005-01-01

    Full Text Available The release of reactive oxygen specie (ROS by activated neutrophil is involved in both the antimicrobial and deleterious effects in chronic inflammation. The objective of the present investigation was to determine the effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory drugs (NSAIDs on the production of ROS by stimulated rat neutrophils. Diclofenac (3.6 µM, indomethacin (12 µM, naproxen (160 µM, piroxicam (13 µM, and tenoxicam (30 µM were incubated at 37ºC in PBS (10 mM, pH 7.4, for 30 min with rat neutrophils (1 x 10(6 cells/ml stimulated by phorbol-12-myristate-13-acetate (100 nM. The ROS production was measured by luminol and lucigenin-dependent chemiluminescence. Except for naproxen, NSAIDs reduced ROS production: 58 ± 2% diclofenac, 90 ± 2% indomethacin, 33 ± 3% piroxicam, and 45 ± 6% tenoxicam (N = 6. For the lucigenin assay, naproxen, piroxicam and tenoxicam were ineffective. For indomethacin the inhibition was 52 ± 5% and diclofenac showed amplification in the light emission of 181 ± 60% (N = 6. Using the myeloperoxidase (MPO/H2O2/luminol system, the effects of NSAIDs on MPO activity were also screened. We found that NSAIDs inhibited both the peroxidation and chlorinating activity of MPO as follows: diclofenac (36 ± 10, 45 ± 3%, indomethacin (97 ± 2, 100 ± 1%, naproxen (56 ± 8, 76 ± 3%, piroxicam (77 ± 5, 99 ± 1%, and tenoxicam (90 ± 2, 100 ± 1%, respectively (N = 3. These results show that therapeutic levels of NSAIDs are able to suppress the oxygen-dependent antimicrobial or oxidative functions of neutrophils by inhibiting the generation of hypochlorous acid.

  19. ASSESSMENT OF PAHS AND SELECTED PESTICIDES IN SHALLOW GROUNDWATER IN THE HIGHEST PROTECTED AREAS IN THE OPOLE REGION, POLAND

    Directory of Open Access Journals (Sweden)

    Mariusz Głowacki

    2014-04-01

    Full Text Available The ground water quality was determined after the analyses of water samples from 18 wells. The wells were in the Groundwater Area with the Highest Protection (Triassic water, Opole region, Poland, rural build up. The water table level was low: 0.5 – 18.0 m below the ground surface level (except for one artesian well. The following parameters were determined: pH, EC, colour, ammonium, nitrite, nitrate, dissolved orthophosphate, total phosphorus, dissolved oxygen, BOD, COD-Mn, COD-Cr, humic substances, chloride, sulphate, total hardness, alkalinity, dry residue PAHs (16 compounds, pesticides (6 compounds, however, only selected data were presented in this paper. In all the analysed water samples chloro-organic pesticides were observed. The analysed water contained heptachlor in the highest concentrations of 15.97 mg/dm3. Good quality water must not include concentrations higher than 0.5 mg/dm3 of heptachlor. However, the concentration was circa 32 times higher than this value. The second pesticide determining poor water quality is dieldrin. This compound in the investigated groundwater was 1.94 mg/dm3 – 4 times higher than the limit for acceptable quality ground water. The concentration of pesticides also changed over the course of the research; the concentration in the analysed groundwater in the same well changed quite dramatically over a period of 1 year. Although PAHs and pesticides are potentially toxic for biological organisms they do exist in the environment as a product of the natural biological transformation of organic matter. The noted concentrations and compositions of PAH compounds were different to natural PAHs. It confirms the fact that agricultural activity influences groundwater quality.

  20. A review on the relation between the brain-serum concentration ratio of drugs and the influence of P-glycoprotein

    DEFF Research Database (Denmark)

    Ejsing, Thomas Broeng; Morling, Niels; Linnet, Kristian

    2007-01-01

    This overview on the brain-serum relationship for drugs illustrates the importance of the drug transporter P-glycoprotein at the blood-brain barrier. Generally, an inverse relationship exists between the magnitude of the brain-serum ratio and the influence of P-glycoprotein. Concerning the pharma...... the pharmacogenomics of P-glycoprotein, no clear effect of single nucleotide polymorphisms (SNPs) has been demonstrated in humans....

  1. A new derivation of the highest-weight polynomial of a unitary lie algebra

    International Nuclear Information System (INIS)

    P Chau, Huu-Tai; P Van, Isacker

    2000-01-01

    A new method is presented to derive the expression of the highest-weight polynomial used to build the basis of an irreducible representation (IR) of the unitary algebra U(2J+1). After a brief reminder of Moshinsky's method to arrive at the set of equations defining the highest-weight polynomial of U(2J+1), an alternative derivation of the polynomial from these equations is presented. The method is less general than the one proposed by Moshinsky but has the advantage that the determinantal expression of the highest-weight polynomial is arrived at in a direct way using matrix inversions. (authors)

  2. The Highest Good and the Practical Regulative Knowledge in Kant’s Critique of Practical Reason

    OpenAIRE

    Joel Thiago Klein

    2016-01-01

    In this paper I defend three different points: first, that the concept of highest good is derived from an a priori but subjective argument, namely a maxim of pure practical reason; secondly, that the theory regarding the highest good has the validity of a practical regulative knowledge; and thirdly, that the practical regulative knowledge can be understood as the same “holding something to be true” as Kant attributes to hope and believe.

  3. Exfoliation in ecstasy: liquid crystal formation and concentration-dependent debundling observed for single-wall nanotubes dispersed in the liquid drug γ-butyrolactone

    Science.gov (United States)

    Bergin, Shane D.; Nicolosi, Valeria; Giordani, Silvia; de Gromard, Antoine; Carpenter, Leslie; Blau, Werner J.; Coleman, Jonathan N.

    2007-11-01

    Large-scale debundling of single-walled nanotubes has been demonstrated by dilution of nanotube dispersions in the solvent γ-butyrolactone. This liquid, sometimes referred to as 'liquid ecstasy', is well known for its narcotic properties. At high concentrations the dispersions form an anisotropic, liquid crystalline phase which can be removed by mild centrifugation. At lower concentrations an isotropic phase is observed with a biphasic region at intermediate concentrations. By measuring the absorbance before and after centrifugation, as a function of concentration, the relative anisotropic and isotropic nanotube concentrations can be monitored. The upper limit of the pure isotropic phase was CNT~0.004 mg ml-1, suggesting that this can be considered the nanotube dispersion limit in γ-butyrolactone. After centrifugation, the dispersions are stable against sedimentation and further aggregation for a period of 8 weeks at least. Atomic-force-microscopy studies on films deposited from the isotropic phase reveal that the bundle diameter distribution decreases dramatically as concentration is decreased. Detailed data analysis suggests the presence of an equilibrium bundle number density. A population of individual nanotubes is always observed which increases with decreasing concentration until almost 40% of all dispersed objects are individual nanotubes at a concentration of 6 × 10-4 mg ml-1. The number density of individual nanotubes peaks at a concentration of ~6 × 10-3 mg ml-1 where almost 10% of the nanotubes by mass are individualized.

  4. Exfoliation in ecstasy: liquid crystal formation and concentration-dependent debundling observed for single-wall nanotubes dispersed in the liquid drug γ-butyrolactone

    International Nuclear Information System (INIS)

    Bergin, Shane D; Nicolosi, Valeria; Giordani, Silvia; Gromard, Antoine de; Carpenter, Leslie; Blau, Werner J; Coleman, Jonathan N

    2007-01-01

    Large-scale debundling of single-walled nanotubes has been demonstrated by dilution of nanotube dispersions in the solvent γ-butyrolactone. This liquid, sometimes referred to as 'liquid ecstasy', is well known for its narcotic properties. At high concentrations the dispersions form an anisotropic, liquid crystalline phase which can be removed by mild centrifugation. At lower concentrations an isotropic phase is observed with a biphasic region at intermediate concentrations. By measuring the absorbance before and after centrifugation, as a function of concentration, the relative anisotropic and isotropic nanotube concentrations can be monitored. The upper limit of the pure isotropic phase was C NT ∼0.004 mg ml -1 , suggesting that this can be considered the nanotube dispersion limit in γ-butyrolactone. After centrifugation, the dispersions are stable against sedimentation and further aggregation for a period of 8 weeks at least. Atomic-force-microscopy studies on films deposited from the isotropic phase reveal that the bundle diameter distribution decreases dramatically as concentration is decreased. Detailed data analysis suggests the presence of an equilibrium bundle number density. A population of individual nanotubes is always observed which increases with decreasing concentration until almost 40% of all dispersed objects are individual nanotubes at a concentration of 6 x 10 -4 mg ml -1 . The number density of individual nanotubes peaks at a concentration of ∼6 x 10 -3 mg ml -1 where almost 10% of the nanotubes by mass are individualized

  5. Population pharmacokinetics/pharmacodynamics of erlotinib and pharmacogenomic analysis of plasma and cerebrospinal fluid drug concentrations in Japanese patients with non-small cell lung cancer.

    Science.gov (United States)

    Fukudo, Masahide; Ikemi, Yasuaki; Togashi, Yosuke; Masago, Katsuhiro; Kim, Young Hak; Mio, Tadashi; Terada, Tomohiro; Teramukai, Satoshi; Mishima, Michiaki; Inui, Ken-Ichi; Katsura, Toshiya

    2013-07-01

    Erlotinib shows large inter-patient pharmacokinetic variability, but the impact of early drug exposure and genetic variations on the clinical outcomes of erlotinib remains fully investigated. The primary objective of this study was to clarify the population pharmacokinetics/pharmacodynamics of erlotinib in Japanese patients with non-small cell lung cancer (NSCLC). The secondary objective was to identify genetic determinant(s) for the cerebrospinal fluid (CSF) permeability of erlotinib and its active metabolite OSI-420. A total of 88 patients treated with erlotinib (150 mg/day) were enrolled, and CSF samples were available from 23 of these patients with leptomeningeal metastases. Plasma and CSF concentrations of erlotinib and OSI-420 were measured by high-performance liquid chromatography with UV detection. Population pharmacokinetic analysis was performed with the nonlinear mixed-effects modelling program NONMEM. Germline mutations including ABCB1 (1236C>T, 2677G>T/A, 3435C>T), ABCG2 (421C>A), and CYP3A5 (6986A>G) polymorphisms, as well as somatic EGFR activating mutations if available, were examined. Early exposure to erlotinib and its safety/efficacy relationship were evaluated. The apparent clearance of erlotinib and OSI-420 were significantly decreased by 24 and 35 % in patients with the ABCG2 421A allele, respectively (p OSI-420 (p model showed that erlotinib trough (C0) levels on day 8 were an independent risk factor for the development of grade ≥2 diarrhea (p = 0.037) and skin rash (p = 0.031). Interstitial lung disease (ILD)-like events occurred in 3 patients (3.4 %), and the median value of erlotinib C0 levels adjacent to these events was approximately 3 times higher than that in patients who did not develop ILD (3253 versus 1107 ng/mL; p = 0.014). The objective response rate in the EGFR wild-type group was marginally higher in patients achieving higher erlotinib C0 levels (≥1711 ng/mL) than that in patients having lower erlotinib C0

  6. Possibility of Predicting Serotonin Transporter Occupancy From the In Vitro Inhibition Constant for Serotonin Transporter, the Clinically Relevant Plasma Concentration of Unbound Drugs, and Their Profiles for Substrates of Transporters.

    Science.gov (United States)

    Yahata, Masahiro; Chiba, Koji; Watanabe, Takao; Sugiyama, Yuichi

    2017-09-01

    Accurate prediction of target occupancy facilitates central nervous system drug development. In this review, we discuss the predictability of serotonin transporter (SERT) occupancy in human brain estimated from in vitro K i values for human SERT and plasma concentrations of unbound drug (C u,plasma ), as well as the impact of drug transporters in the blood-brain barrier. First, the geometric means of in vitro K i values were compared with the means of in vivo K i values (K i,u,plasma ) which were calculated as C u,plasma values at 50% occupancy of SERT obtained from previous clinical positron emission tomography/single photon emission computed tomography imaging studies for 6 selective serotonin transporter reuptake inhibitors and 3 serotonin norepinephrine reuptake inhibitors. The in vitro K i values for 7 drugs were comparable to their in vivo K i,u,plasma values within 3-fold difference. SERT occupancy was overestimated for 5 drugs (P-glycoprotein substrates) and underestimated for 2 drugs (presumably uptake transporter substrates, although no evidence exists as yet). In conclusion, prediction of human SERT occupancy from in vitro K i values and C u,plasma was successful for drugs that are not transporter substrates and will become possible in future even for transporter substrates, once the transporter activities will be accurately estimated from in vitro experiments. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  7. [The gender gap in highest quality medical research - A scientometric analysis of the representation of female authors in highest impact medical journals].

    Science.gov (United States)

    Bendels, Michael H K; Wanke, Eileen M; Benik, Steffen; Schehadat, Marc S; Schöffel, Norman; Bauer, Jan; Gerber, Alexander; Brüggmann, Dörthe; Oremek, Gerhard M; Groneberg, David A

    2018-05-01

     The study aims to elucidate the state of gender equality in high-impact medical research, analyzing the representation of female authorships from January, 2008 to September, 2017.  133 893 male and female authorships from seven high-impact medical journals were analyzed. The key methodology was the combined analysis of the relative frequency, odds ratio and citations of female authorships. The Prestige Index measures the distribution of prestigious authorships between the two genders.  35.0 % of all authorships and 34.3 % of the first, 36.1 % of the co- and 24.2 % of the last authorships were held by women. Female authors have an odds ratio of 0.97 (KI: 0.93 - 1.01) for first, 1.36 (KI: 1.32 - 1.40) for co- und 0.57 (KI: 0.54 - 0.60) for last authorships compared to male authors. The proportion of female authorships exhibits an annual growth of 1.3 % overall, with 0.5 % for first, 1.2 % for co-, and 0.8 % for last authorships. Women are underrepresented at prestigious authorship compared to men (Prestige Index = -0.38). The underrepresentation accentuates in highly competitive articles attracting the highest citation rates, namely, articles with many authors and articles that were published in highest-impact journals. Multi-author articles with male key authors are more frequently cited than articles with female key authors. The gender-specific differences in citation rates increase the more authors contribute to an article. Women publish fewer articles compared to men (39.6 % female authors are responsible for 35.0 % of the authorships) and are underrepresented at productivity levels of more than 1 article per author. Distinct differences at the country level were revealed.  High impact medical research is characterized by few female group leaders as last authors and many female researchers being first or co-authors early in their career. It is very likely that this gender-specific career dichotomy will persistent in

  8. Exfoliation in ecstasy: liquid crystal formation and concentration-dependent debundling observed for single-wall nanotubes dispersed in the liquid drug {gamma}-butyrolactone

    Energy Technology Data Exchange (ETDEWEB)

    Bergin, Shane D [School of Physics, Trinity College Dublin, University of Dublin, Dublin 2 (Ireland); Nicolosi, Valeria [School of Physics, Trinity College Dublin, University of Dublin, Dublin 2 (Ireland); Giordani, Silvia [School of Physics, Trinity College Dublin, University of Dublin, Dublin 2 (Ireland); Gromard, Antoine de [School of Physics, Trinity College Dublin, University of Dublin, Dublin 2 (Ireland); Carpenter, Leslie [School of Physics, Trinity College Dublin, University of Dublin, Dublin 2 (Ireland); Blau, Werner J [School of Physics, Trinity College Dublin, University of Dublin, Dublin 2 (Ireland); Coleman, Jonathan N [School of Physics, Trinity College Dublin, University of Dublin, Dublin 2 (Ireland)

    2007-11-14

    Large-scale debundling of single-walled nanotubes has been demonstrated by dilution of nanotube dispersions in the solvent {gamma}-butyrolactone. This liquid, sometimes referred to as 'liquid ecstasy', is well known for its narcotic properties. At high concentrations the dispersions form an anisotropic, liquid crystalline phase which can be removed by mild centrifugation. At lower concentrations an isotropic phase is observed with a biphasic region at intermediate concentrations. By measuring the absorbance before and after centrifugation, as a function of concentration, the relative anisotropic and isotropic nanotube concentrations can be monitored. The upper limit of the pure isotropic phase was C{sub NT}{approx}0.004 mg ml{sup -1}, suggesting that this can be considered the nanotube dispersion limit in {gamma}-butyrolactone. After centrifugation, the dispersions are stable against sedimentation and further aggregation for a period of 8 weeks at least. Atomic-force-microscopy studies on films deposited from the isotropic phase reveal that the bundle diameter distribution decreases dramatically as concentration is decreased. Detailed data analysis suggests the presence of an equilibrium bundle number density. A population of individual nanotubes is always observed which increases with decreasing concentration until almost 40% of all dispersed objects are individual nanotubes at a concentration of 6 x 10{sup -4} mg ml{sup -1}. The number density of individual nanotubes peaks at a concentration of {approx}6 x 10{sup -3} mg ml{sup -1} where almost 10% of the nanotubes by mass are individualized.

  9. Determination of the total concentration of highly protein-bound drugs in plasma by on-line dialysis and column liquid chromatography: application to non-steroidal anti-inflammatory drugs.

    NARCIS (Netherlands)

    Herraez-Hernandez, R.; van de Merbel, N.C.; Brinkman, U.A.T.

    1995-01-01

    The potential of on-line dialysis as a sample preparation procedure for compounds highly bound to plasma proteins is evaluated, using non-steroidal anti-inflammatory drugs as model compounds and column liquid chromatography as the separation technique. Different strategies to reduce the degree of

  10. Determination of the total concentration of highly protein-bound drugs in plasma by on-line dialysis and column liquid chromatography : application to non-steroidal anti-inflammatory drugs

    NARCIS (Netherlands)

    Herráez-Hernández, R; van de Merbel, N C; Brinkman, U A

    1995-01-01

    The potential of on-line dialysis as a sample preparation procedure for compounds highly bound to plasma proteins is evaluated, using non-steroidal anti-inflammatory drugs as model compounds and column liquid chromatography as the separation technique. Different strategies to reduce the degree of

  11. Determination of optical properties, drug concentration, and tissue oxygenation in human pleural tissue before and after Photofrin-mediated photodynamic therapy

    Science.gov (United States)

    Ong, Yi Hong; Padawer-Curry, Jonah; Finlay, Jarod C.; Kim, Michele M.; Dimofte, Andreea; Cengel, Keith; Zhu, Timothy C.

    2018-02-01

    PDT efficacy depends on the concentration of photosensitizer, oxygen, and light delivery in patient tissues. In this study, we measure the in-vivo distribution of important dosimetric parameters, namely the tissue optical properties (absorption μa (λ) and scattering μs ' (λ) coefficients), photofrin concentration (cphotofrin), blood oxygen saturation (%StO2), and total hemoglobin concentration (THC), before and after PDT. We characterize the inter- and intra-patient heterogeneity of these quantities and explore how these properties change as a result of PDT treatment. The result suggests the need for real-time dosimetry during PDT to optimize the treatment condition depending on the optical and physiological properties.

  12. Dipole model analysis of highest precision HERA data, including very low Q"2's

    International Nuclear Information System (INIS)

    Luszczak, A.; Kowalski, H.

    2016-12-01

    We analyse, within a dipole model, the final, inclusive HERA DIS cross section data in the low χ region, using fully correlated errors. We show, that these highest precision data are very well described within the dipole model framework starting from Q"2 values of 3.5 GeV"2 to the highest values of Q"2=250 GeV"2. To analyze the saturation effects we evaluated the data including also the very low 0.35< Q"2 GeV"2 region. The fits including this region show a preference of the saturation ansatz.

  13. The Experience Elicited by Hallucinogens Presents the Highest Similarity to Dreaming within a Large Database of Psychoactive Substance Reports

    Science.gov (United States)

    Sanz, Camila; Zamberlan, Federico; Erowid, Earth; Erowid, Fire; Tagliazucchi, Enzo

    2018-01-01

    Ever since the modern rediscovery of psychedelic substances by Western society, several authors have independently proposed that their effects bear a high resemblance to the dreams and dreamlike experiences occurring naturally during the sleep-wake cycle. Recent studies in humans have provided neurophysiological evidence supporting this hypothesis. However, a rigorous comparative analysis of the phenomenology (“what it feels like” to experience these states) is currently lacking. We investigated the semantic similarity between a large number of subjective reports of psychoactive substances and reports of high/low lucidity dreams, and found that the highest-ranking substance in terms of the similarity to high lucidity dreams was the serotonergic psychedelic lysergic acid diethylamide (LSD), whereas the highest-ranking in terms of the similarity to dreams of low lucidity were plants of the Datura genus, rich in deliriant tropane alkaloids. Conversely, sedatives, stimulants, antipsychotics, and antidepressants comprised most of the lowest-ranking substances. An analysis of the most frequent words in the subjective reports of dreams and hallucinogens revealed that terms associated with perception (“see,” “visual,” “face,” “reality,” “color”), emotion (“fear”), setting (“outside,” “inside,” “street,” “front,” “behind”) and relatives (“mom,” “dad,” “brother,” “parent,” “family”) were the most prevalent across both experiences. In summary, we applied novel quantitative analyses to a large volume of empirical data to confirm the hypothesis that, among all psychoactive substances, hallucinogen drugs elicit experiences with the highest semantic similarity to those of dreams. Our results and the associated methodological developments open the way to study the comparative phenomenology of different altered states of consciousness and its relationship with non-invasive measurements of brain physiology. PMID

  14. The Experience Elicited by Hallucinogens Presents the Highest Similarity to Dreaming within a Large Database of Psychoactive Substance Reports

    Directory of Open Access Journals (Sweden)

    Camila Sanz

    2018-01-01

    Full Text Available Ever since the modern rediscovery of psychedelic substances by Western society, several authors have independently proposed that their effects bear a high resemblance to the dreams and dreamlike experiences occurring naturally during the sleep-wake cycle. Recent studies in humans have provided neurophysiological evidence supporting this hypothesis. However, a rigorous comparative analysis of the phenomenology (“what it feels like” to experience these states is currently lacking. We investigated the semantic similarity between a large number of subjective reports of psychoactive substances and reports of high/low lucidity dreams, and found that the highest-ranking substance in terms of the similarity to high lucidity dreams was the serotonergic psychedelic lysergic acid diethylamide (LSD, whereas the highest-ranking in terms of the similarity to dreams of low lucidity were plants of the Datura genus, rich in deliriant tropane alkaloids. Conversely, sedatives, stimulants, antipsychotics, and antidepressants comprised most of the lowest-ranking substances. An analysis of the most frequent words in the subjective reports of dreams and hallucinogens revealed that terms associated with perception (“see,” “visual,” “face,” “reality,” “color”, emotion (“fear”, setting (“outside,” “inside,” “street,” “front,” “behind” and relatives (“mom,” “dad,” “brother,” “parent,” “family” were the most prevalent across both experiences. In summary, we applied novel quantitative analyses to a large volume of empirical data to confirm the hypothesis that, among all psychoactive substances, hallucinogen drugs elicit experiences with the highest semantic similarity to those of dreams. Our results and the associated methodological developments open the way to study the comparative phenomenology of different altered states of consciousness and its relationship with non-invasive measurements of brain

  15. An integrated approach to care attracts people living with HIV who use illicit drugs in an urban centre with a concentrated HIV epidemic

    Directory of Open Access Journals (Sweden)

    S. Fernando

    2016-11-01

    Full Text Available Abstract Background People living with HIV (PLHIV who are also marginalized by social and structural inequities often face barriers to accessing and adhering to HIV treatment and care. The Dr. Peter Centre (DPC is a non-profit integrated care facility with a supervised injection room that serves PLHIV experiencing multiple barriers to social and health services in Vancouver, Canada. This study examines whether the DPC is successful in drawing in PLHIV with complex health issues, including addiction. Methods Using data collected by the Longitudinal Investigations into Supportive and Ancillary health services (LISA study from July 2007 to January 2010, linked with clinical variables available through the British Columbia Centre for Excellence in HIV/AIDS Drug Treatment Program, we identified DPC and non-DPC clients with a history of injection drug use. Bivariable and multivariable logistic regression analyses compared socio-demographic and clinical characteristics of DPC clients (n = 76 and non-DPC clients (n = 482 with a history of injection drug use. Results Of the 917 LISA participants included within this analysis, 100 (10.9% reported being a DPC client, of which 76 reported a history of injection drug use. Adjusted results found that compared to non-DPC clients with a history of injection drug use, DPC-clients were more likely to be male (AOR: 4.18, 95% CI = 2.09–8.37; use supportive services daily vs. less than daily (AOR: 3.16, 95% CI = 1.79–5.61; to have been diagnosed with a mental health disorder (AOR: 2.11; 95% CI: 1.12–3.99; to have a history of interpersonal violence (AOR: 2.76; 95% CI: 1.23–6.19; and to have ever experienced ART interruption longer than 1 year (AOR: 2.39; 95% CI: 1.38–4.15. Conclusions Our analyses suggest that the DPC operating care model engages PLHIV with complex care needs, highlighting that integrated care facilities are needed to support the multiple intersecting vulnerabilities faced

  16. Subtoxic Concentrations of Hepatotoxic Drugs Lead to Kupffer Cell Activation in a Human In Vitro Liver Model: An Approach to Study DILI

    Directory of Open Access Journals (Sweden)

    Victoria Kegel

    2015-01-01

    Full Text Available Drug induced liver injury (DILI is an idiosyncratic adverse drug reaction leading to severe liver damage. Kupffer cells (KC sense hepatic tissue stress/damage and therefore could be a tool for the estimation of consequent effects associated with DILI. Aim of the present study was to establish a human in vitro liver model for the investigation of immune-mediated signaling in the pathogenesis of DILI. Hepatocytes and KC were isolated from human liver specimens. The isolated KC yield was 1.2±0.9×106 cells/g liver tissue with a purity of >80%. KC activation was investigated by the measurement of reactive oxygen intermediates (ROI, DCF assay and cell activity (XTT assay. The initial KC activation levels showed broad donor variability. Additional activation of KC using supernatants of hepatocytes treated with hepatotoxic drugs increased KC activity and led to donor-dependent changes in the formation of ROI compared to KC incubated with supernatants from untreated hepatocytes. Additionally, a compound- and donor-dependent increase in proinflammatory cytokines or in anti-inflammatory cytokines was detected. In conclusion, KC related immune signaling in hepatotoxicity was successfully determined in a newly established in vitro liver model. KC were able to detect hepatocyte stress/damage and to transmit a donor- and compound-dependent immune response via cytokine production.

  17. Subtoxic Concentrations of Hepatotoxic Drugs Lead to Kupffer Cell Activation in a Human In Vitro Liver Model: An Approach to Study DILI

    Science.gov (United States)

    Kegel, Victoria; Pfeiffer, Elisa; Burkhardt, Britta; Liu, Jia L.; Zeilinger, Katrin; Nüssler, Andreas K.; Seehofer, Daniel; Damm, Georg

    2015-01-01

    Drug induced liver injury (DILI) is an idiosyncratic adverse drug reaction leading to severe liver damage. Kupffer cells (KC) sense hepatic tissue stress/damage and therefore could be a tool for the estimation of consequent effects associated with DILI. Aim of the present study was to establish a human in vitro liver model for the investigation of immune-mediated signaling in the pathogenesis of DILI. Hepatocytes and KC were isolated from human liver specimens. The isolated KC yield was 1.2 ± 0.9 × 106 cells/g liver tissue with a purity of >80%. KC activation was investigated by the measurement of reactive oxygen intermediates (ROI, DCF assay) and cell activity (XTT assay). The initial KC activation levels showed broad donor variability. Additional activation of KC using supernatants of hepatocytes treated with hepatotoxic drugs increased KC activity and led to donor-dependent changes in the formation of ROI compared to KC incubated with supernatants from untreated hepatocytes. Additionally, a compound- and donor-dependent increase in proinflammatory cytokines or in anti-inflammatory cytokines was detected. In conclusion, KC related immune signaling in hepatotoxicity was successfully determined in a newly established in vitro liver model. KC were able to detect hepatocyte stress/damage and to transmit a donor- and compound-dependent immune response via cytokine production. PMID:26491234

  18. Correlation of the highest-energy cosmic rays with the positions of nearby active galactic nuclei

    NARCIS (Netherlands)

    Abraham, J.; Abreu, P.; Aglietta, M.; Aguirre, C.; Allard, D.; Allekotte, I.; Allen, J.; Allison, P.; Alvarez-Muniz, J.; Ambrosio, M.; Anchordoqui, L.; Andringa, S.; Anzalone, A.; Aramo, C.; Argiro, S.; Arisaka, K.; Armengaud, E.; Arneodo, F.; Arqueros, F.; Asch, T.; Asorey, H.; Assis, P.; Atulugama, B. S.; Aublin, J.; Ave, M.; Avila, G.; Baecker, T.; Badagnani, D.; Barbosa, A. F.; Barnhill, D.; Barroso, S. L. C.; Bauleo, P.; Beatty, J. J.; Beau, T.; Becker, B. R.; Becker, K. H.; Bellido, J. A.; BenZvi, S.; Berat, C.; Bergmann, T.; Bernardini, P.; Bertou, X.; Biermann, P. L.; Billoir, P.; Blanch-Bigas, O.; Blanco, F.; Blasi, P.; Bleve, C.; Bluemer, H.; Bohacova, M.; Bonifazi, C.; Bonino, R.; Brack, J.; Brogueira, P.; Brown, W. C.; Buchholz, P.; Bueno, A.; Burton, R. E.; Busca, N. G.; Caballero-Mora, K. S.; Cai, B.; Camin, D. V.; Caramete, L.; Caruso, R.; Carvalho, W.; Castellina, A.; Catalano, O.; Cataldi, G.; Cazon, L.; Cester, R.; Chauvin, J.; Chiavassa, A.; Chinellato, J. A.; Chou, A.; Chye, J.; Clay, R. W.; Colombo, E.; Conceicao, R.; Connolly, B.; Contreras, F.; Coppens, J.; Cordier, A.; Cotti, U.; Coutu, S.; Covault, C. E.; Creusot, A.; Criss, A.; Cronin, J.; Curutiu, A.; Dagoret-Campagne, S.; Daumiller, K.; Dawson, B. R.; de Almeida, R. M.; De Donato, C.; Bg, S. J. de Jong; De La Vega, G.; de Mello, W. J. M.; de Mello Neto, J. R. T.; De Mitri, I.; de Souza, V.; del Peral, L.; Deligny, O.; Della Selva, A.; Delle Fratte, C.; Dembinski, H.; Di Giulio, C.; Diaz, J. C.; Diep, P. N.; Dobrigkeit, C.; D'Olivo, J. C.; Dong, P. N.; Dornic, D.; Dorofeev, A.; dos Anjos, J. C.; Dova, M. T.; D'Urso, D.; Dutan, I.; DuVernois, M. A.; Engel, R.; Epele, L.; Escobar, C. O.; Etchegoyen, A.; Luis, P. Facal San; Falcke, H.; Farrar, G.; Fauth, A. C.; Fazzini, N.; Ferrer, F.; Ferry, S.; Fick, B.; Filevich, A.; Filipcic, A.; Fleck, I.; Fracchiolla, C. E.; Fulgione, W.; Garcia, B.; Gaimez, D. Garcia; Garcia-Pinto, D.; Garrido, X.; Geenen, H.; Gelmini, G.; Gemmeke, H.; Ghia, P. L.; Giller, M.; Glass, H.; Gold, M. S.; Golup, G.; Albarracin, F. Gomez; Berisso, M. Gomez; Herrero, R. Gomez; Goncalves, P.; do Amaral, M. Goncalves; Gonzalez, D.; Gonzalezc, J. G.; Gonzalez, M.; Gora, D.; Gorgi, A.; Gouffon, P.; Grassi, V.; Grillo, A. F.; Grunfeld, C.; Guardincerri, Y.; Guarino, F.; Guedes, G. P.; Gutierrez, J.; Hague, J. D.; Hamilton, J. C.; Hansen, P.; Harari, D.; Harmsma, S.; Harton, J. L.; Haungs, A.; Hauschildt, T.; Healy, M. D.; Hebbeker, T.; Hebrero, G.; Heck, D.; Hojvat, C.; Holmes, V. C.; Homola, P.; Hoerandel, J.; Horneffer, A.; Horvat, M.; Hrabovsky, M.; Huege, T.; Hussain, M.; Larlori, M.; Insolia, A.; Ionita, F.; Italiano, A.; Kaducak, M.; Kampert, K. H.; Karova, T.; Kegl, B.; Keilhauer, B.; Kemp, E.; Kieckhafer, R. M.; Klages, H. O.; Kleifges, M.; Kleinfeller, J.; Knapik, R.; Knapp, J.; Koanga, V. -H.; Krieger, A.; Kroemer, O.; Kuempel, D.; Kunka, N.; Kusenko, A.; La Rosa, G.; Lachaud, C.; Lago, B. L.; Lebrun, D.; LeBrun, P.; Lee, J.; de Oliveira, M. A. Leigui; Lopez, R.; Letessier-Selvon, A.; Leuthold, M.; Lhenry-Yvon, I.; Aguera, A. Lopez; Bahilo, J. Lozano; Garcia, R. Luna; Maccarone, M. C.; Macolino, C.; Maldera, S.; Mancarella, G.; Mancenido, M. E.; Mandatat, D.; Mantsch, P.; Mariazzi, A. G.; Maris, I. C.; Falcon, H. R. Marquez; Martello, D.; Martinez, J.; Bravo, O. Martinez; Mathes, H. J.; Matthews, J.; Matthews, J. A. J.; Matthiae, G.; Maurizio, D.; Mazur, P. O.; McCauley, T.; McEwen, M.; McNeil, R. R.; Medina, M. C.; Medina-Tanco, G.; Meli, A.; Melo, D.; Menichetti, E.; Menschikov, A.; Meurer, Chr.; Meyhandan, R.; Micheletti, M. I.; Miele, G.; Miller, W.; Mollerach, S.; Monasor, M.; Ragaigne, D. Monnier; Montanet, F.; Morales, B.; Morello, C.; Moreno, J. C.; Morris, C.; Mostafa, M.; Muller, M. A.; Mussa, R.; Navarra, G.; Navarro, J. L.; Navas, S.; Necesal, P.; Nellen, L.; Newman-Holmes, C.; Newton, D.; Nhung, P. T.; Nierstenhoefer, N.; Nitz, D.; Nosek, D.; Nozka, L.; Oehlschlaeger, J.; Ohnuki, T.; Olinto, A.; Olmos-Gilbaja, V. M.; Ortiz, M.; Ortolani, F.; Ostapchenko, S.; Otero, L.; Pacheco, N.; Selmi-Dei, D. Pakk; Palatka, M.; Pallotta, J.; Parente, G.; Parizot, E.; Parlati, S.; Pastor, S.; Patel, M.; Paul, T.; Pavlidou, V.; Payet, K.; Pech, M.; Pekala, J.; Pelayo, R.; Pepe, I. M.; Perrone, L.; Petrera, S.; Petrinca, P.; Petrov, Y.; Pichel, A.; Piegaia, R.; Pierog, T.; Pimenta, M.; Pinto, T.; Pirronello, V.; Pisanti, O.; Platino, M.; Pochon, J.; Privitera, P.; Prouza, M.; Quel, E. J.; Rautenberg, J.; Redondo, A.; Reucroft, S.; Revenu, B.; Rezende, F. A. S.; Ridky, J.; Riggi, S.; Risse, M.; Riviere, C.; Rizi, V.; Roberts, M.; Robledo, C.; Rodriguez, G.; Martino, J. Rodriguez; Rojo, J. Rodriguez; Rodriguez-Cabo, I.; Rodriguez-Frias, M. D.; Ros, G.; Rosado, J.; Roth, M.; Rouille-d'Orfeuil, B.; Roulet, E.; Roverok, A. C.; Salamida, F.; Salazar, H.; Salina, G.; Sanchez, F.; Santander, M.; Santo, C. E.; Santos, E. M.; Sarazin, F.; Sarkar, S.; Sato, R.; Scherini, V.; Schieler, H.; Schmidt, A.; Schmidt, F.; Schmidt, T.; Scholten, O.; Schovanek, P.; Schuessler, F.; Sciutto, S. J.; Scuderi, M.; Segreto, A.; Semikoz, D.; Settimo, M.; Shellard, R. C.; Sidelnik, I.; Siffert, B. B.; Sigl, G.; De Grande, N. Smetniansky; Smialkowski, A.; Smida, R.; Smith, A. G. K.; Smith, B. E.; Snow, G. R.; Sokolsky, P.; Sommers, P.; Sorokin, J.; Spinka, H.; Squartini, R.; Strazzeri, E.; Stutz, A.; Suarez, F.; Suomijarvi, T.; Supanitsky, A. D.; Sutherland, M. S.; Swain, J.; Szadkowski, Z.; Takahashi, J.; Tamashiro, A.; Tamburro, A.; Tascau, O.; Tcaciuc, R.; Thao, N. T.; Thomas, D.; Ticona, R.; Tiffenberg, J.; Timmermans, C.; Tkaczyk, W.; Peixoto, C. J. Todero; Tome, B.; Tonachini, A.; Torres, I.; Travnicek, P.; Tripathi, A.; Tristram, G.; Tscherniakhovski, D.; Tueros, M.; Ulrich, R.; Unger, M.; Urban, M.; Galicia, J. F. Valdes; Valino, I.; Valore, L.; van den Berg, A. M.; van Elewyck, V.; Vazquez, R. A.; Veberic, D.; Veiga, A.; Velarde, A.; Venters, T.; Verzi, V.; Videla, M.; Villasenor, L.; Vorobiov, S.; Voyvodic, L.; Wahlberg, H.; Wainberg, O.; Warner, D.; Watson, A. A.; Westerhoff, S.; Wieczorek, G.; Wiencke, L.; Wilczynska, B.; Wilczynski, H.; Wileman, C.; Winnick, M. G.; Wu, H.; Wundheiler, B.; Yamamoto, T.; Younk, P.; Zas, E.; Zavrtanik, D.; Zavrtanik, M.; Zech, A.; Zepeda, A.; Ziolkowski, M.

    Data collected by the Pierre Auger Observatory provide evidence for anisotropy in the arrival directions of the cosmic rays with the highest-energies, which are correlated with the positions of relatively nearby active galactic nuclei (AGN) [Pierre Auger Collaboration, Science 318 (2007) 938]. The

  19. Alpha-1-antitrypsin deficiency in Madeira (Portugal): the highest prevalence in the world.

    Science.gov (United States)

    Spínola, Carla; Bruges-Armas, Jácome; Pereira, Conceição; Brehm, António; Spínola, Hélder

    2009-10-01

    Alpha-1-antitrypsin (AAT) deficiency is a common genetic disease which affects both lung and liver. Early diagnosis can help asymptomatic patients to adjust their lifestyle choices in order to reduce the risk of Chronic Obstructive Pulmonary Disease (COPD). The determination of this genetic deficiency prevalence in Madeira Island (Portugal) population is important to clarify susceptibility and define the relevance of performing genetic tests for AAT on individuals at risk for COPD. Two hundred samples of unrelated individuals from Madeira Island were genotyped for the two most common AAT deficiency alleles, PI*S and PI*Z, using Polymerase Chain Reaction-Mediated Site-Directed Mutagenesis. Our results show one of the highest frequencies for both mutations when compared to any already studied population in the world. In fact, PI*S mutation has the highest prevalence (18%), and PI*Z mutation (2.5%) was the third highest worldwide. The frequency of AAT deficiency genotypes in Madeira (PI*ZZ, PI*SS, and PI*SZ) is estimated to be the highest in the world: 41 per 1000. This high prevalence of AAT deficiency on Madeira Island reveals an increased genetic susceptibility to COPD and suggests a routine genetic testing for individuals at risk.

  20. Effects of Spray-Drying and Choice of Solid Carriers on Concentrations of Labrasol® and Transcutol® in Solid Self-Microemulsifying Drug Delivery Systems (SMEDDS

    Directory of Open Access Journals (Sweden)

    Christopher Wai-Kei Lam

    2013-01-01

    Full Text Available Solid self-microemulsifying drug delivery systems (SMEDDS have been used increasingly for improving the bioavailability of hydrophobic drugs. Labrasol® and Transcutol® are used widely as surfactant and solubilizer in the formulation of solid SMEDDS. We investigated the effects of spray-drying and the use of different solid carriers on concentrations of Labrasol® and Transcutol® in solid SMEDDS with scutellarin as the formulated drug. Liquid and gas chromatography tandem mass spectrometry (LC-MS and GC-MS methods were developed for measuring low concentrations of Labrasol® and Transcutol®. In the preparation of solid SMEDDS, lactose, hydroxypropylmethyl cellulose (HPMC and microcrystalline cellulose (MCC were used as solid carriers. Judging from the retention ratios of Labrasol® and Transcutol®, the droplet size of solid SMEDDS increased after spray-drying of liquid SMEDDS, and concentrations of these excipients decreased after the solidifying procedure. In such reduction, Lactose and HPMC were found to preserve Labrasol® and Transcutol® better than MCC during spray-drying, and the resultant droplet sizes were smaller than that of MCC. Labrasol® and Transcutol® showed good thermal stability at 60 °C degree for 10 days. It can be concluded that spray-drying could increase the droplet size of solid SMEDDS and decreased the concentration of Labrasol® and Transcutol® therein, while water-soluble solid carriers could preserve Labrasol® and Transcutol® better than insoluble carriers in the solid SMEDDS.

  1. Human drug metabolism: an introduction

    National Research Council Canada - National Science Library

    Coleman, Michael D

    2010-01-01

    ... metabolism and its impact on patient welfare. After underlining the relationship between efficacy, toxicity and drug concentration, the book then considers how metabolizing systems operate and how they impact upon drug concentration...

  2. Administration of the non-steroidal anti-inflammatory drug ibuprofen increases macrophage concentrations but reduces necrosis during modified muscle use

    Science.gov (United States)

    Cheung, E. V.; Tidball, J. G.

    2003-01-01

    OBJECTIVE: To test the hypothesis that ibuprofen administration during modified muscle use reduces muscle necrosis and invasion by select myeloid cell populations. METHODS: Rats were subjected to hindlimb unloading for 10 days, after which they experienced muscle reloading by normal weight-bearing to induce muscle inflammation and necrosis. Some animals received ibuprofen by intraperitoneal injection 8 h prior to the onset of muscle reloading, and then again at 8 and 16 h following the onset of reloading. Other animals received buffer injection at 8 h prior to reloading and then ibuprofen at 8 and 16 h following the onset of reloading. Control animals received buffer only at each time point. Quantitative immunohistochemical analysis was used to assess the presence of necrotic muscle fibers, total inflammatory infiltrate, neutrophils, ED1+ macrophages and ED2+ macrophages at 24 h following the onset of reloading. RESULT: Administration of ibuprofen beginning 8 h prior to reloading caused significant reduction in the concentration of necrotic fibers, but increased the concentration of inflammatory cells in muscle. The increase in inflammatory cells was attributable to a 2.6-fold increase in the concentration of ED2+ macrophages. Animals treated with ibuprofen 8 h following the onset of reloading showed no decrease in muscle necrosis or increase in ED2+ macrophage concentrations. CONCLUSION: Administration of ibuprofen prior to increased muscle loading reduces muscle damage, but increases the concentration of macrophages that express the ED2 antigen. The increase in ED2+ macrophage concentration and decrease in necrosis may be mechanistically related because ED2+ macrophages have been associated with muscle regeneration and repair.

  3. Drug Facts

    Medline Plus

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

  4. Highest manageable level of radioactivity in the waste storage facilities of power plants

    International Nuclear Information System (INIS)

    Elkert, J.; Lennartsson, R.

    1991-01-01

    This project presents and discusses an investigation of the highest level of radioactivity possible to handle in the waste storage facilities. The amount of radioactivity, about 0.1% of the fuel inventory, is the same in both of the cases but the amount of water is very different. The hypothetical accident was supposed to be damage of the reactor fuel caused by loss of coolant. (K.A.E.)

  5. Highest cited papers published in Neurology India: An analysis for the years 1993-2014.

    Science.gov (United States)

    Pandey, Paritosh; Subeikshanan, V; Madhugiri, Venkatesh S

    2016-01-01

    The highest cited papers published in a journal provide a snapshot of the clinical practice and research in that specialty and/or region. The aim of this study was to determine the highest cited papers published in Neurology India and analyze their attributes. This study was a citation analysis of all papers published in Neurology India since online archiving commenced in 1993. All papers published in Neurology India between the years 1993-2014 were listed. The number of times each paper had been cited up till the time of performing this study was determined by performing a Google Scholar search. Published papers were then ranked on the basis of total times cited since publication and the annual citation rate. Statistical Techniques: Simple counts and percentages were used to report most results. The mean citations received by papers in various categories were compared using the Student's t-test or a one-way analysis of variance, as appropriate. All analyses were carried out on SAS University Edition (SAS/STAT®, SAS Institute Inc, NC, USA) and graphs were generated on MS Excel 2016. The top papers on the total citations and annual citation rate rank lists pertained to basic neuroscience research. The highest cited paper overall had received 139 citations. About a quarter of the papers published had never been cited at all. The major themes represented were vascular diseases and infections. The highest cited papers reflect the diseases that are of major concern in India. Certain domains such as trauma, allied neurosciences, and basic neuroscience research were underrepresented.

  6. ATLAS event at 13 TeV - Highest mass dijets resonance event in 2015 data

    CERN Multimedia

    ATLAS Collaboration

    2015-01-01

    The highest-mass, central dijet event passing the dijet resonance selection collected in 2015 (Event 1273922482, Run 280673) : the two central high-pT jets have an invariant mass of 6.9 TeV, the two leading jets have a pT of 3.2 TeV. The missing transverse momentum in this event is 46 GeV.

  7. ATLAS event at 13 TeV - Highest mass dijets angular event in 2015 data

    CERN Multimedia

    ATLAS Collaboration

    2015-01-01

    The highest-mass dijet event passing the angular selection collected in 2015 (Event 478442529, Run 280464): the two central high-pT jets have an invariant mass of 7.9 TeV, the three leading jets have a pT of 1.99, 1.86 and 0.74 TeV respectively. The missing transverse momentum in this event is 46 GeV

  8. Eyebrow hairs from actinic keratosis patients harbor the highest number of cutaneous human papillomaviruses.

    Science.gov (United States)

    Schneider, Ines; Lehmann, Mandy D; Kogosov, Vlada; Stockfleth, Eggert; Nindl, Ingo

    2013-04-24

    Cutaneous human papillomavirus (HPV) infections seem to be associated with the onset of actinic keratosis (AK). This study compares the presence of cutaneous HPV types in eyebrow hairs to those in tissues of normal skin and skin lesions of 75 immunocompetent AK patients. Biopsies from AK lesions, normal skin and plucked eyebrow hairs were collected from each patient. DNA from these specimens was tested for the presence of 28 cutaneous HPV (betaPV and gammaPV) by a PCR based method. The highest number of HPV prevalence was detected in 84% of the eyebrow hairs (63/75, median 6 types) compared to 47% of AK lesions (35/75, median 3 types) (pAK and 69 in normal skin. In all three specimens HPV20, HPV23 and/or HPV37 were the most prevalent types. The highest number of multiple types of HPV positive specimens was found in 76% of the eyebrow hairs compared to 60% in AK and 57% in normal skin. The concordance of at least one HPV type in virus positive specimens was 81% (three specimens) and 88-93% of all three combinations with two specimens. Thus, eyebrow hairs revealed the highest number of cutaneous HPV infections, are easy to collect and are an appropriate screening tool in order to identify a possible association of HPV and AK.

  9. In vitro killing of Escherichia coli, Staphylococcus pseudintermedius and Pseudomonas aeruginosa by enrofloxacin in combination with its active metabolite ciprofloxacin using clinically relevant drug concentrations in the dog and cat.

    Science.gov (United States)

    Blondeau, J M; Borsos, S; Blondeau, L D; Blondeau, B J

    2012-03-23

    Enrofloxacin is a fluoroquinolone antibacterial agent used to treat infections in companion animals. Enrofloxacin's antimicrobial spectrum includes Gram positive and Gram-negative bacteria and demonstrates concentration-dependent bacteriocidal activity. In dogs and cats, enrofloxacin is partially metabolized to ciprofloxacin and both active agents circulate simultaneously in treated animals at ratios of approximately 60-70% enrofloxacin to 30-40% ciprofloxacin. We were interested in determining the killing of companion animal isolates of Escherichia coli, Staphylococcus pseudintermedius and Pseudomonas aeruginosa by enrofloxacin and ciprofloxacin combined using clinically relevant drug concentrations and ratios. For E. coli isolates exposed to 2.1 and 4.1μg/ml of enrofloxacin/ciprofloxacin at 50:50, 60:40 and 70:30 ratios, a 1.7-2.5log(10) reduction (94-99% kill) was seen following 20min of drug exposure; 0.89-1.7log(10) (92-99% kill) of S. pseudintermedius following 180min of drug exposure; 0.85-3.4log(10) (98-99% kill) of P. aeruginosa following 15min of drug exposure. Killing of S. pseudintermedius was enhanced in the presence of enrofloxacin whereas killing of P. aeruginosa was enhanced in the presence of ciprofloxacin. Antagonism was not seen when enrofloxacin and ciprofloxacin were used in kill assays. The unique feature of partial metabolism of enrofloxacin to ciprofloxacin expands the spectrum of enhanced killing of common companion animal pathogens. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Highest recorded electrical conductivity and microstructure in polypropylene-carbon nanotubes composites and the effect of carbon nanofibers addition

    Science.gov (United States)

    Ramírez-Herrera, C. A.; Pérez-González, J.; Solorza-Feria, O.; Romero-Partida, N.; Flores-Vela, A.; Cabañas-Moreno, J. G.

    2018-04-01

    In the last decade, numerous investigations have been devoted to the preparation of polypropylene-multiwalled carbon nanotubes (PP/MWCNT) nanocomposites having enhanced properties, and in particular, high electrical conductivities (> 1 S cm-1). The present work establishes that the highest electrical conductivity in PP/MWCNT nanocomposites is limited by the amount of nanofiller content which can be incorporated in the polymer matrix, namely, about 20 wt%. This concentration of MWCNT in PP leads to a maximum electrical conductivity slightly lower than 8 S cm-1, but only by assuring an adequate combination of dispersion and spatial distribution of the carbon nanotubes. The realization of such an optimal microstructure depends on the characteristics of the production process of the PP/MWCNT nanocomposites; in our experiments, involving composite fabrication by melt mixing and hot pressing, a second re-processing cycle is shown to increase the electrical conductivity values by up to two orders of magnitude, depending on the MWCNT content of the nanocomposite. A modest increase of the highest electrical conductivity obtained in nanocomposites with 21.5 wt% MWCNT content has been produced by the combined use of carbon nanofibers (CNF) and MWCNT, so that the total nanofiller content was increased to 30 wt% in the nanocomposite with PP—15 wt% MWCNT—15 wt%CNF.

  11. Production of human metabolites by gastrointestinal bacteria as a potential source of post-mortem alteration of antemortem drug/metabolite concentrations.

    Science.gov (United States)

    Martindale, Stephanie M; Powers, Robert H; Bell, Suzanne C

    2015-01-01

    Previous studies have demonstrated that bacterial species are capable of transforming complex chemical substances. Several of these species, native to the human gastrointestinal tract, are active in postmortem decomposition. They have potential to cause biotransformations affecting compound-to-metabolite ratios within the human body, especially after death. Investigation of postmortem effects could supply valuable information, especially concerning compound identification and confirmation. The purpose of this research was to investigate the effects of Escherichia coli, Bacteroides fragilis, and Clostridium perfringens on diazepam and flunitrazepam in Reinforced Clostridial Medium, and to compare bacterial biotransformation products to those of human metabolism. A decrease in diazepam concentration between pre- and post-incubation was observed for samples inoculated with Escherichia coli (14.7-20.2%) as well as Bacteroides fragilis (13.9-25.7%); however there was no corresponding increase in concentration for the monitored human metabolites. Flunitrazepam demonstrated a greater concentration loss when incubated with individual bacterial species as well as mixed culture (79.2-100.0%). Samples incubated with Bacteroides fragilis, Clostridium perfringens, and mixed culture resulted in nearly complete conversion of flunitrazepam. Increased 7-aminoflunitrazepam concentrations accounted for the majority of the conversion; however discrepancies in the mass balance of the reaction suggested the possibility of a minor metabolite that was not monitored in the current analysis. These experiments served as a pilot study and proof of concept that can be adapted and applied to a realm of possibilities. Ultimately, this methodology would be ideal to study compounds that are too toxic or lethal for animal and human metabolic investigations. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Measurement of adherence, drug concentrations and the effectiveness of artemether-lumefantrine, chlorproguanil-dapsone or sulphadoxine-pyrimethamine in the treatment of uncomplicated malaria in Malawi

    Directory of Open Access Journals (Sweden)

    Chimpeni Phillips

    2009-08-01

    Full Text Available Abstract Background Sulphadoxine-pyrimethamine (SP is the only single dose therapy for uncomplicated malaria, but there is widespread resistance. At the time of this study, artemether-lumefantrine (AL and chlorproguanil-dapsone (CPD, both multi-dose regimes, were considered possible alternatives to SP in Malawi. The aim of this study was to investigate the impact of poor adherence on the effectiveness of AL and CPD. Methods Children ≥12 months and adults with uncomplicated malaria were randomized to receive AL, CPD or SP. Adherence was measured using a questionnaire and electronic monitoring devices, MEMS™, pill bottles that recorded the date and time of opening. Day-7 plasma dapsone or lumefantrine concentrations were measured to examine their relationship with adherence and clinical response. Results 841 patients were recruited. The day-28 adequate clinical and parasitological response (ACPR rates, using intention to treat analysis (missing data treated as failure, were AL 85.2%, CPD 63.7% and SP 50%. ACPR rates for AL were higher than CPD or SP on days 28 and 42 (p ≤ 0.002 for all comparisons. CPD was more effective than SP on day-28 (p = 0.01, but not day-42. Very high adherence was reported using the questionnaire, 100% for AL treated patients and 99.2% for the CPD group. Only three CPD participants admitted missing any doses. 164/181 (90.6% of CPD treated patients took all their doses out of the MEMS™ container and they were more likely to have a day-28 ACPR than those who did not take all their medication out of the container, p = 0.024. Only 7/87 (8% AL treated patients did not take all of their doses out of their MEMS™ container and none had treatment failure. Median day-7 dapsone concentrations were higher in CPD treated patients with ACPR than in treatment failures, p = 0.012. There were no differences in day-7 dapsone or lumefantrine concentrations between those who took all their doses from the MEMS™ container and those

  13. Eyebrow hairs from actinic keratosis patients harbor the highest number of cutaneous human papillomaviruses

    Science.gov (United States)

    2013-01-01

    Background Cutaneous human papillomavirus (HPV) infections seem to be associated with the onset of actinic keratosis (AK). This study compares the presence of cutaneous HPV types in eyebrow hairs to those in tissues of normal skin and skin lesions of 75 immunocompetent AK patients. Methods Biopsies from AK lesions, normal skin and plucked eyebrow hairs were collected from each patient. DNA from these specimens was tested for the presence of 28 cutaneous HPV (betaPV and gammaPV) by a PCR based method. Results The highest number of HPV prevalence was detected in 84% of the eyebrow hairs (63/75, median 6 types) compared to 47% of AK lesions (35/75, median 3 types) (p< 0.001) and 37% of normal skin (28/75, median 4 types) (p< 0.001), respectively. A total of 228 HPV infections were found in eyebrow hairs compared to only 92 HPV infections in AK and 69 in normal skin. In all three specimens HPV20, HPV23 and/or HPV37 were the most prevalent types. The highest number of multiple types of HPV positive specimens was found in 76% of the eyebrow hairs compared to 60% in AK and 57% in normal skin. The concordance of at least one HPV type in virus positive specimens was 81% (three specimens) and 88-93% of all three combinations with two specimens. Conclusions Thus, eyebrow hairs revealed the highest number of cutaneous HPV infections, are easy to collect and are an appropriate screening tool in order to identify a possible association of HPV and AK. PMID:23618013

  14. 17-Year-Old Boy with Renal Failure and the Highest Reported Creatinine in Pediatric Literature

    Directory of Open Access Journals (Sweden)

    Vimal Master Sankar Raj

    2015-01-01

    Full Text Available The prevalence of chronic kidney disease (CKD is on the rise and constitutes a major health burden across the world. Clinical presentations in early CKD are usually subtle. Awareness of the risk factors for CKD is important for early diagnosis and treatment to slow the progression of disease. We present a case report of a 17-year-old African American male who presented in a life threatening hypertensive emergency with renal failure and the highest reported serum creatinine in a pediatric patient. A brief discussion on CKD criteria, complications, and potential red flags for screening strategies is provided.

  15. Observations of the highest energy gamma-rays from gamma-ray bursts

    International Nuclear Information System (INIS)

    Dingus, Brenda L.

    2001-01-01

    EGRET has extended the highest energy observations of gamma-ray bursts to GeV gamma rays. Such high energies imply the fireball that is radiating the gamma-rays has a bulk Lorentz factor of several hundred. However, EGRET only detected a few gamma-ray bursts. GLAST will likely detect several hundred bursts and may extend the maximum energy to a few 100 GeV. Meanwhile new ground based detectors with sensitivity to gamma-ray bursts are beginning operation, and one recently reported evidence for TeV emission from a burst

  16. Addressing the Highest Risk: Environmental Programs at Los Alamos National Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Forbes, Elaine E [Los Alamos National Laboratory

    2012-06-08

    Report topics: Current status of cleanup; Shift in priorities to address highest risk; Removal of above-ground waste; and Continued focus on protecting water resources. Partnership between the National Nuclear Security Administration's Los Alamos Site Office, DOE Carlsbad Field Office, New Mexico Environment Department, and contractor staff has enabled unprecedented cleanup progress. Progress on TRU campaign is well ahead of plan. To date, have completed 130 shipments vs. 104 planned; shipped 483 cubic meters of above-ground waste (vs. 277 planned); and removed 11,249 PE Ci of material at risk (vs. 9,411 planned).

  17. Automatic orbital GTAW welding: Highest quality welds for tomorrow's high-performance systems

    Science.gov (United States)

    Henon, B. K.

    1985-01-01

    Automatic orbital gas tungsten arc welding (GTAW) or TIG welding is certain to play an increasingly prominent role in tomorrow's technology. The welds are of the highest quality and the repeatability of automatic weldings is vastly superior to that of manual welding. Since less heat is applied to the weld during automatic welding than manual welding, there is less change in the metallurgical properties of the parent material. The possibility of accurate control and the cleanliness of the automatic GTAW welding process make it highly suitable to the welding of the more exotic and expensive materials which are now widely used in the aerospace and hydrospace industries. Titanium, stainless steel, Inconel, and Incoloy, as well as, aluminum can all be welded to the highest quality specifications automatically. Automatic orbital GTAW equipment is available for the fusion butt welding of tube-to-tube, as well as, tube to autobuttweld fittings. The same equipment can also be used for the fusion butt welding of up to 6 inch pipe with a wall thickness of up to 0.154 inches.

  18. Optimasi Penggunaan Lahan Kosong di Kecamatan Baturiti Untuk Properti Komersial Dengan Prinsip Highest and Best Use

    Directory of Open Access Journals (Sweden)

    Made Darmawan Saputra Mahardika

    2013-09-01

    Full Text Available Kecamatan Baturiti merupakan satu-satunya kecamatan di Kabupaten Tabanan yang berkembang dalam sektor ekonomi agrowisata karena lokasinya yang strategis dekat dengan berbagai obyek wisata terkenal. Dengan lokasi yang strategis, pembangunan untuk properti komersial tentu akan memberikan potensi keuntungan tinggi bagi investor yang memiliki lahan kosong di Kecamatan Baturiti. Kondisi seperti ini menyebabkan permintaan yang tinggi akan lahan, padahal ketersediaan lahan selalu berkurang. Pembangunan properti komersial di Kecamatan Baturiti perlu dioptimalisasi agar dicapai keuntungan maksimum bagi investor. Berdasarkan hal tersebut, investor yang ingin membangun di Kecamatan Baturiti memerlukan analisa untuk mendapatkan alternatif pemanfaatan lahan kosong. Lahan yang dianalisa merupakan lahan kosong belum terbangun seluas 22.175 m2 di Kecamatan Baturiti, Kabupaten Tabanan. Metode yang digunakan untuk mengetahui alternatif pendirian bangunan komersial yang memiliki nilai pasar tertinggi adalah Highest and Best Use (HBU. Dengan metode tersebut, pemilik lahan dapat mengetahui alternatif terbaik yang memenuhi syarat-syarat diijinkan secara legal, memungkinkan secara fisik, layak secara finansial, dan memiliki produktivitas maksimum. Hasil yang diperoleh dari analisa Highest and Best Use ini adalah alternatif mixed-use berupa hotel dan toko souvenir dengan nilai lahan tertinggi dibandingkan alternatif lainnya sebesar Rp 7,950,714.60 per m2.

  19. A novel method to predict the highest hardness of plasma sprayed coating without micro-defects

    Science.gov (United States)

    Zhuo, Yukun; Ye, Fuxing; Wang, Feng

    2018-04-01

    The plasma sprayed coatings are stacked by splats, which are regarded generally as the elementary units of coating. Many researchers have focused on the morphology and formation mechanism of splat. However, a novel method to predict the highest hardness of plasma sprayed coating without micro-defects is proposed according to the nanohardness of splat in this paper. The effectiveness of this novel method was examined by experiments. Firstly, the microstructure of splats and coating, meanwhile the 3D topography of the splats were observed by SEM (SU1510) and video microscope (VHX-2000). Secondly, the nanohardness of splats was evaluated by nanoindentation (NHT) in order to be compared with microhardness of coating measured by microhardness tester (HV-1000A). The results show that the nanohardness of splats with diameter of 70 μm, 100 μm and 140 μm were in the scope of 11∼12 GPa while the microhardness of coating were in the range of 8∼9 GPa. Because the splats had not micro-defects such as pores and cracks in the nanohardness evaluated nano-zone, the nanohardness of the splats can be utilized to predict the highest hardness of coating without micro-defects. This method indicates the maximum of sprayed coating hardness and will reduce the test number to get high hardness coating for better wear resistance.

  20. Drug Facts

    Medline Plus

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

  1. Drug Facts

    Medline Plus

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

  2. Drug Facts

    Medline Plus

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

  3. Effect of vitamin D3, other drugs altering serum calcium or phosphorus concentrations, and desoxycorticosterone on the distribution of Tc-99m pyrophosphate between target and nontarget tissues

    International Nuclear Information System (INIS)

    Carr, E.A. Jr.; Carroll, M.; Montes, M.

    1981-01-01

    Radioactive imaging agents are chemically designed for selective distribution. Another approach to selectivity is to find stable compounds that favorably influence this distribution. Using a rat model of myocardial necrosis, we studied effects of various stable compounds (as a single, large dose or fractionated into short series) on the ratio, uptake of Tc-99m pyrophosphate (PPi) by the target lesion/uptake by the principal nontarget, bone (L/B). Vitamin D3s ability to increase L/B was mediated by the hypercalcemia and hyperphosphatemia that it caused. The hypercalcemia was accompanied by increased [Ca] in the lesion. In contrast, pulse doses of desoxycorticosterone acetate (DOCA) at 7 and 6 hr before killing increased uptake by lesion, increasing L/B from 0.19 +/- 0.03 to 0.45 +/- 0.08 (p less than 0.01), with no change in serum [Ca] and minimal changes in serum [P], [Na], and [K]. DOCA also increased the lesion-to-blood ratio from 6.5 +/- 0.07 to 15.4 +/- 3.9 (p less than 0.05). These results encourage further study of DOCA's effect and investigation of other stable drugs that may influence distribution of other imaging agents

  4. Stereocomplex-Reinforced PEGylated Polylactide Micelle for Optimized Drug Delivery

    Directory of Open Access Journals (Sweden)

    Chunsheng Feng

    2016-04-01

    Full Text Available The instability of PEGylated polylactide micelles is a challenge for drug delivery. Stereocomplex interaction between racemic polylactide chains with different configurations provides an effective strategy to enhance the stability of micelles as the nanocarriers of drugs. In this work, a stereocomplex micelle (SCM self-assembled from the amphiphilic triblock copolymers comprising poly(ethylene glycol (PEG, and dextrorotatory and levorotatory polylactides (PDLA and PLLA was applied for efficient drug delivery. The spherical SCM showed the smallest scale and the lowest critical micelle concentration (CMC than the micelles with single components attributed to the stereocomplex interaction between PDLA and PLLA. 10-Hydroxycamptothecin (HCPT as a model antitumor drug was loaded into micelles. Compared with the loading micelles from individual PDLA and PLLA, the HCPT-loaded SCM exhibited the highest drug loading efficiency (DLE and the slowest drug release in phosphate-buffered saline (PBS at pH 7.4, indicating its enhanced stability in circulation. More fascinatingly, the laden SCM was demonstrated to have the highest cellular uptake of HCPT and suppress malignant cells most effectively in comparison to the HCPT-loaded micelles from single copolymer. In summary, the stereocomplex-enhanced PLA–PEG–PLA micelle may be promising for optimized drug delivery in the clinic.

  5. Analisa Highest and Best Use Pada Lahan Kosong Di Jemur Gayungan II Surabaya

    Directory of Open Access Journals (Sweden)

    Finda Virgitta Faradiany

    2014-09-01

    Full Text Available Perkembangan bisnis properti di Surabaya yang semakin pesat, mengakibatkan permintaan terhadap lahan semakin tinggi. Namun fakta di lapangan menampakkan hal yang sebaliknya karena ternyata masih terdapat lahan-lahan yang dibiarkan kosong tidak dimanfaatkan oleh pemiliknya. Kondisi yang demikian memerlukan efisiensi dan optimalisasi penggunaan lahan dengan mendirikan sebuah properti komersial yang memberikan keuntungan bagi pemilik serta lingkungan sekitarnya.Lahan “X” seluas 1786 m2 berlokasi di Jl. Jemur Gayungan II merupakan lahan kosong yang terletak di dekat daerah perkantoran dan berpotensi dikembangkan menjadi properti komersial. Penentuan nilai lahan “X” bergantung pada penggunaan lahan. Metode penilaian yang digunakan adalah analisa penggunaan tertinggi dan terbaik atau Highest and Best Use (HBU yang secara legal diijinkan, secara fisik memungkinkan, layak secara finansial dan memiliki produktifitas maksimum. Dari hasil penelitian didapatkan alternatif yang menghasilkan nilai lahan tertinggi dan produktivitas maksimum adalah hotel. Nilai lahan yang didapatkan sebesar Rp 9.722.718/m2 dengan produktivitas meningkat sebesar 486%.

  6. Soil pollution from motor car emissions in the highest region of the Tauern mountains autobahn

    International Nuclear Information System (INIS)

    Kasperowski, E.; Frank, E.

    1990-01-01

    In a pilot study, pollutant loads from motor traffic were investigated and quantified in soils and grassland near the autobahn. Near the motorway, increased concentrations of inorganic and organic pollutants were found, depending on distance, both in soil and in grassland. The decreased soil life is also attributed to this. (orig.) [de

  7. Failure of ETV in patients with the highest ETV success scores.

    Science.gov (United States)

    Gianaris, Thomas J; Nazar, Ryan; Middlebrook, Emily; Gonda, David D; Jea, Andrew; Fulkerson, Daniel H

    2017-09-01

    OBJECTIVE Endoscopic third ventriculostomy (ETV) is a surgical alternative to placing a CSF shunt in certain patients with hydrocephalus. The ETV Success Score (ETVSS) is a reliable, simple method to estimate the success of the procedure by 6 months of postoperative follow-up. The highest score is 90, estimating a 90% chance of the ETV effectively treating hydrocephalus without requiring a shunt. Treatment with ETV fails in certain patients, despite their being the theoretically best candidates for the procedure. In this study the authors attempted to identify factors that further predicted success in patients with the highest ETVSSs. METHODS A retrospective review was performed of all patients treated with ETV at 3 institutions. Demographic, radiological, and clinical data were recorded. All patients by definition were older than 1 year, had obstructive hydrocephalus, and did not have a prior shunt. Failure of ETV was defined as the need for a shunt by 1 year. The ETV was considered a success if the patient did not require another surgery (either shunt placement or a repeat endoscopic procedure) by 1 year. A statistical analysis was performed to identify factors associated with success or failure. RESULTS Fifty-nine patients met the entry criteria for the study. Eleven patients (18.6%) required further surgery by 1 year. All of these patients received a shunt. The presenting symptom of lethargy statistically correlated with success (p = 0.0126, odds ratio [OR] = 0.072). The preoperative radiological finding of transependymal flow (p = 0.0375, OR 0.158) correlated with success. A postoperative larger maximum width of the third ventricle correlated with failure (p = 0.0265). CONCLUSIONS The preoperative findings of lethargy and transependymal flow statistically correlated with success. This suggests that the best candidates for ETV are those with a relatively acute elevation of intracranial pressure. Cases without these findings may represent the failures in this

  8. The highest velocity and the shortest duration permitting attainment of VO2max during running

    Directory of Open Access Journals (Sweden)

    Tiago Turnes

    2015-02-01

    Full Text Available DOI: http://dx.doi.org/10.5007/1980-0037.2015v17n2p226   The severe-intensity domain has important applications for the prescription of running training and the elaboration of experimental designs. The objectives of this study were: 1 to investigate the validity of a previously proposed model to estimate the shortest exercise duration (TLOW and the highest velocity (VHIGH at which VO2max is reached during running, and 2 to evaluate the effects of aerobic training status on these variables. Eight runners and eight physically active subjects performed several treadmill running exercise tests to fatigue in order to mathematically estimate and to experimentally determine TLOW and VHIGH. The relationship between the time to achieve VO2max and time to exhaustion (Tlim was used to estimate TLOW. VHIGH was estimated using the critical velocity model. VHIGH was assumed to be the highest velocity at which VO2 was equal to or higher than the average VO2max minus one standard deviation. TLOW was defined as Tlim associated with VHIGH. Runners presented better aerobic fitness and higher VHIGH (22.2 ± 1.9 km.h-1 than active subjects (20.0 ± 2.1 km.h-1. However, TLOW did not differ between groups (runners: 101 ± 39 s; active subjects: 100 ± 35 s. TLOW and VHIGH were not well estimated by the model proposed, with high coefficients of variation (> 6% and a low correlation coefficient (r<0.70, a fact reducing the validity of the model. It was concluded that aerobic training status positively affected only VHIGH. Furthermore, the model proposed presented low validity to estimate the upper boundary of the severe-intensity domain (i.e., VHIGH, irrespective of the subjects’ training status.

  9. Drug: D08821 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08821 Drug Concentrated human red blood cells; Red cells concentrates -leukocytes... reduced (RCC-LR) (TN); Irradiated red cells concentrates -leukocytes reduced (Ir-RCC-LR) (TN) ... PubChem: 96025504 ...

  10. African American Women: Surviving Breast Cancer Mortality against the Highest Odds

    Directory of Open Access Journals (Sweden)

    Shelley White-Means

    2015-12-01

    Full Text Available Among the country’s 25 largest cities, the breast cancer mortality disparity is highest in Memphis, Tennessee, where African American women are twice as likely to die from breast cancer as White women. This qualitative study of African-American breast cancer survivors explores experiences during and post treatment that contributed to their beating the high odds of mortality. Using a semi-structured interview guide, a focus group session was held in 2012 with 10 breast cancer survivors. Thematic analysis and a deductive a priori template of codes were used to analyze the data. Five main themes were identified: family history, breast/body awareness and preparedness to manage a breast cancer event, diagnosis experience and reaction to the diagnosis, family reactions, and impact on life. Prayer and family support were central to coping, and survivors voiced a cultural acceptance of racial disparities in health outcomes. They reported lack of provider sensitivity regarding pain, financial difficulties, negative responses from family/friends, and resiliency strategies for coping with physical and mental limitations. Our research suggested that a patient-centered approach of demystifying breast cancer (both in patient-provider communication and in community settings would impact how women cope with breast cancer and respond to information about its diagnosis.

  11. THE IMPACT OF FREQUENCY STANDARDS ON COHERENCE IN VLBI AT THE HIGHEST FREQUENCIES

    Energy Technology Data Exchange (ETDEWEB)

    Rioja, M.; Dodson, R. [ICRAR, University of Western Australia, Perth (Australia); Asaki, Y. [Institute of Space and Astronautical Science, 3-1-1 Yoshinodai, Chuou, Sagamihara, Kanagawa 252-5210 (Japan); Hartnett, J. [School of Physics, University of Western Australia, Perth (Australia); Tingay, S., E-mail: maria.rioja@icrar.org [ICRAR, Curtin University, Perth (Australia)

    2012-10-01

    We have carried out full imaging simulation studies to explore the impact of frequency standards in millimeter and submillimeter very long baseline interferometry (VLBI), focusing on the coherence time and sensitivity. In particular, we compare the performance of the H-maser, traditionally used in VLBI, to that of ultra-stable cryocooled sapphire oscillators over a range of observing frequencies, weather conditions, and analysis strategies. Our simulations show that at the highest frequencies, the losses induced by H-maser instabilities are comparable to those from high-quality tropospheric conditions. We find significant benefits in replacing H-masers with cryocooled sapphire oscillator based frequency references in VLBI observations at frequencies above 175 GHz in sites which have the best weather conditions; at 350 GHz we estimate a 20%-40% increase in sensitivity over that obtained when the sites have H-masers, for coherence losses of 20%-10%, respectively. Maximum benefits are to be expected by using co-located Water Vapor Radiometers for atmospheric correction. In this case, we estimate a 60%-120% increase in sensitivity over the H-maser at 350 GHz.

  12. Exchange Interactions on the Highest-Spin Reported Molecule: the Mixed-Valence Fe42 Complex

    Science.gov (United States)

    Aravena, Daniel; Venegas-Yazigi, Diego; Ruiz, Eliseo

    2016-04-01

    The finding of high-spin molecules that could behave as conventional magnets has been one of the main challenges in Molecular Magnetism. Here, the exchange interactions, present in the highest-spin molecule published in the literature, Fe42, have been analysed using theoretical methods based on Density Functional Theory. The system with a total spin value S = 45 is formed by 42 iron centres containing 18 high-spin FeIII ferromagnetically coupled and 24 diamagnetic low-spin FeII ions. The bridging ligands between the two paramagnetic centres are two cyanide ligands coordinated to the diamagnetic FeII cations. Calculations were performed using either small Fe4 or Fe3 models or the whole Fe42 complex, showing the presence of two different ferromagnetic couplings between the paramagnetic FeIII centres. Finally, Quantum Monte Carlo simulations for the whole system were carried out in order to compare the experimental and simulated magnetic susceptibility curves from the calculated exchange coupling constants with the experimental one. This comparison allows for the evaluation of the accuracy of different exchange-correlation functionals to reproduce such magnetic properties.

  13. Analisis Highest and Best Use (HBU pada Lahan Jl. Gubeng Raya No. 54 Surabaya

    Directory of Open Access Journals (Sweden)

    Akmaluddin Akmaluddin

    2013-03-01

    Full Text Available Laju pertumbuhan penduduk dan tingkat perekonomian yang semakin meningkat di  kota-kota besar seperti Surabaya, bertolak belakang dengan  ketersediaan lahan yang terbatas. Selayaknya properti yang akan dibangun di atas suatu lahan dapat memberikan manfaat yang maksimal serta efisien agar hasilnya dapat dirasakan demi pembangunan wilayah tersebut. Oleh karena itu, perlu dilakukan perhitungan  penggunaan yang paling memungkinkan dan diizinkan dari suatu tanah kosong atau tanah yang  sudah dibangun, dimana secara fisik dimungkinkan, didukung atau dibenarkan oleh peraturan, layak secara keuangan dan menghasilkan nilai tertinggi. Dalam penelitian ini dilakukan analisis Highest and Best Use (HBU pada lahan di Jl. Gubeng Raya No. 54 Surabaya seluas 1.150 m2 yang direncanakan akan dibangun hotel. Lahan tersebut berpotensi untuk dikembangkan menjadi properti komersial seperti hotel, apartemen, perkantoran dan pertokoan. Analisis tersebut menggunakan tinjauan terhadap aspek fisik, legal, finansial dan produktivitas maksimumnya. Dari hasil penelitian ini didapatkan alternatif properti komersial hotel yang memiliki penggunaan tertinggi dan terbaik pada pemanfaatan lahan dengan nilai lahan Rp. 67.069.980,31/ m2.

  14. Analisa Alternatif Revitalisasi Pasar Gubeng Masjid Surabaya dengan Metode Highest And Best Use

    Directory of Open Access Journals (Sweden)

    Marsha Swalia Mustika

    2017-01-01

    Full Text Available Dalam era globalisasi ini banyak bermunculan pasar-pasar modern yang dibangun dengan segala kelebihan dan fasilitasnya. Munculnya pasar-pasar modern membuat keberadaan pasar tradisional tersudut, tidak terkecuali Pasar Gubeng Masjid Surabaya. Namun keberadaan pasar yang strategis yaitu dekat dengan perkantoran, hotel dan pusat perbelanjaan, serta stasiun kereta api membuat pasar tersebut memiliki potensi untuk dikembangkan menjadi properti yang memberikan nilai lahan tertinggi dan terbaik. Oleh karena itu, perlu dilakukan analisa Highest and Best Use (HBU yang dapat memberikan masukan untuk melakukan investasi terbaik. Analisa HBU ini menggunakan empat kriteria yaitu secara fisik dimungkinkan, secara legal diizinkan , secara finansial layak, dan memiliki produktivitas maksimum. Alternatif yang memiliki produktivitas maksimum tersebut dapat dijadikan sebagai nilai lahan tertinggi dan terbaik pada lahan Pasar Gubeng Masjid Surabaya. Dari hasil penelitian didapatkan alternatif yang menghasilkan nilai lahan tertinggi dan produktivitas maksimum adalah alternatif pengembangan multi use pasar dengan pusat perbelanjaan.. Nilai lahan yang didapatkan sebesar Rp 46.946.524,-/m2 dengan produktivitas meningkat sebesar 312%.

  15. Transitional care for the highest risk patients: findings of a randomised control study

    Directory of Open Access Journals (Sweden)

    Kheng Hock Lee

    2015-10-01

    Full Text Available Background: Interventions to prevent readmissions of patients at highest risk have not been rigorously evaluated. We conducted a randomised controlled trial to determine if a post-discharge transitional care programme can reduce readmissions of such patients in Singapore. Methods: We randomised 840 patients with two or more unscheduled readmissions in the prior 90 days and Length of stay, Acuity of admission, Comorbidity of patient, Emergency department utilisation score ≥10 to the intervention programme (n = 419 or control (n = 421. Patients allocated to the intervention group received post-discharge surveillance by a multidisciplinary integrated care team and early review in the clinic. The primary outcome was the proportion of patients with at least one unscheduled readmission within 30 days after discharge. Results: We found no statistically significant reduction in readmissions or emergency department visits in patients on the intervention group compared to usual care. However, patients in the intervention group reported greater patient satisfaction (p < 0.001. Conclusion: Any beneficial effect of interventions initiated after discharge is small for high-risk patients with multiple comorbidity and complex care needs. Future transitional care interventions should focus on providing the entire cycle of care for such patients starting from time of admission to final transition to the primary care setting. Trial Registration: Clinicaltrials.gov, no NCT02325752

  16. Transitional care for the highest risk patients: findings of a randomised control study

    Directory of Open Access Journals (Sweden)

    Kheng Hock Lee

    2015-10-01

    Full Text Available Background: Interventions to prevent readmissions of patients at highest risk have not been rigorously evaluated. We conducted a randomised controlled trial to determine if a post-discharge transitional care programme can reduce readmissions of such patients in Singapore.Methods: We randomised 840 patients with two or more unscheduled readmissions in the prior 90 days and Length of stay, Acuity of admission, Comorbidity of patient, Emergency department utilisation score ≥10 to the intervention programme (n = 419 or control (n = 421. Patients allocated to the intervention group received post-discharge surveillance by a multidisciplinary integrated care team and early review in the clinic. The primary outcome was the proportion of patients with at least one unscheduled readmission within 30 days after discharge.Results: We found no statistically significant reduction in readmissions or emergency department visits in patients on the intervention group compared to usual care. However, patients in the intervention group reported greater patient satisfaction (p < 0.001.Conclusion: Any beneficial effect of interventions initiated after discharge is small for high-risk patients with multiple comorbidity and complex care needs. Future transitional care interventions should focus on providing the entire cycle of care for such patients starting from time of admission to final transition to the primary care setting.Trial Registration: Clinicaltrials.gov, no NCT02325752

  17. A System with a Choice of Highest-Bidder-First and FIFO Services

    Directory of Open Access Journals (Sweden)

    Tejas Bodas

    2015-02-01

    Full Text Available Service systems using a highest-bidder-first (HBF policy have been studied in queueing literature for various applications and in economics literature to model corruption. Such systems have applications in modern problems like scheduling jobs in cloud computing scenarios or placement of ads on web pages. However, using a HBF service is like using a spot market and may not be preferred by many users. For such users, it may be good to provide a simple scheduler, e.g., a FIFO service. Further, in some situations it may even be necessary that a free service queue operates alongside a HBF queue. Motivated by such a scenario, we propose and analyze a service system with a FIFO server and a HBF server in parallel. Arriving customers are from a heterogeneous population with different valuations of their delay costs. They strategically choose between FIFO and HBF service; if HBF is chosen, they also choose the bid value to optimize an individual cost. We characterize the Wardrop equilibrium in such a system and analyze the revenue to the server. We see that when the total capacity is fixed and is shared between the FIFO and HBF servers, revenue is maximised when the FIFO capacity is non zero. However, if the FIFO server is added to an HBF server, then the revenue decreases with increasing FIFO capacity. We also discuss the case when customers are allowed to balk.

  18. African American Women: Surviving Breast Cancer Mortality against the Highest Odds

    Science.gov (United States)

    White-Means, Shelley; Rice, Muriel; Dapremont, Jill; Davis, Barbara; Martin, Judy

    2015-01-01

    Among the country’s 25 largest cities, the breast cancer mortality disparity is highest in Memphis, Tennessee, where African American women are twice as likely to die from breast cancer as White women. This qualitative study of African-American breast cancer survivors explores experiences during and post treatment that contributed to their beating the high odds of mortality. Using a semi-structured interview guide, a focus group session was held in 2012 with 10 breast cancer survivors. Thematic analysis and a deductive a priori template of codes were used to analyze the data. Five main themes were identified: family history, breast/body awareness and preparedness to manage a breast cancer event, diagnosis experience and reaction to the diagnosis, family reactions, and impact on life. Prayer and family support were central to coping, and survivors voiced a cultural acceptance of racial disparities in health outcomes. They reported lack of provider sensitivity regarding pain, financial difficulties, negative responses from family/friends, and resiliency strategies for coping with physical and mental limitations. Our research suggested that a patient-centered approach of demystifying breast cancer (both in patient-provider communication and in community settings) would impact how women cope with breast cancer and respond to information about its diagnosis. PMID:26703655

  19. A cosmopolitan design of teacher education and a progressive orientation towards the highest good

    Directory of Open Access Journals (Sweden)

    Klas Roth

    2013-01-01

    Full Text Available In this paper I discuss a Kantian conception of cosmopolitan education. It suggests that we pursue the highest good – an object of morality – in the world together, and requires that we acknowledge the value of freedom, render ourselves both efficacious and autonomous in practice, cultivate our judgment, and unselfishly co-operate in the co-ordination and fulfilment of our morally permissible ends. Now, such an accomplishment is one of the most difficult challenges, and may not be achieved in our time, if ever. In the first part of the paper I show that we, according to Kant, have to interact with each other, and comply with the moral law in the quest of general happiness, not merely personal happiness. In the second part, I argue that a cosmopolitan design of teacher education in Kantian terms can establish moral character, even though good moral character is ultimately the outcome of free choice. Such a design can do so by optimizing the freedom of those concerned to set and pursue their morally permissible ends, and to cultivate their judgment through the use of examples. This requires, inter alia, that they be enabled, and take responsibility, to think for themselves, in the position of everyone else, and consistently; and to strengthen their virtue or self-mastery to comply, in practice, with the moral law.

  20. Oxygen pathway modeling estimates high reactive oxygen species production above the highest permanent human habitation.

    Directory of Open Access Journals (Sweden)

    Isaac Cano

    Full Text Available The production of reactive oxygen species (ROS from the inner mitochondrial membrane is one of many fundamental processes governing the balance between health and disease. It is well known that ROS are necessary signaling molecules in gene expression, yet when expressed at high levels, ROS may cause oxidative stress and cell damage. Both hypoxia and hyperoxia may alter ROS production by changing mitochondrial Po2 (PmO2. Because PmO2 depends on the balance between O2 transport and utilization, we formulated an integrative mathematical model of O2 transport and utilization in skeletal muscle to predict conditions to cause abnormally high ROS generation. Simulations using data from healthy subjects during maximal exercise at sea level reveal little mitochondrial ROS production. However, altitude triggers high mitochondrial ROS production in muscle regions with high metabolic capacity but limited O2 delivery. This altitude roughly coincides with the highest location of permanent human habitation. Above 25,000 ft., more than 90% of exercising muscle is predicted to produce abnormally high levels of ROS, corresponding to the "death zone" in mountaineering.

  1. Towards highest peak intensities for ultra-short MeV-range ion bunches

    Science.gov (United States)

    Busold, Simon; Schumacher, Dennis; Brabetz, Christian; Jahn, Diana; Kroll, Florian; Deppert, Oliver; Schramm, Ulrich; Cowan, Thomas E.; Blažević, Abel; Bagnoud, Vincent; Roth, Markus

    2015-01-01

    A laser-driven, multi-MeV-range ion beamline has been installed at the GSI Helmholtz center for heavy ion research. The high-power laser PHELIX drives the very short (picosecond) ion acceleration on μm scale, with energies ranging up to 28.4 MeV for protons in a continuous spectrum. The necessary beam shaping behind the source is accomplished by applying magnetic ion lenses like solenoids and quadrupoles and a radiofrequency cavity. Based on the unique beam properties from the laser-driven source, high-current single bunches could be produced and characterized in a recent experiment: At a central energy of 7.8 MeV, up to 5 × 108 protons could be re-focused in time to a FWHM bunch length of τ = (462 ± 40) ps via phase focusing. The bunches show a moderate energy spread between 10% and 15% (ΔE/E0 at FWHM) and are available at 6 m distance to the source und thus separated from the harsh laser-matter interaction environment. These successful experiments represent the basis for developing novel laser-driven ion beamlines and accessing highest peak intensities for ultra-short MeV-range ion bunches. PMID:26212024

  2. Medical school dropout--testing at admission versus selection by highest grades as predictors.

    Science.gov (United States)

    O'Neill, Lotte; Hartvigsen, Jan; Wallstedt, Birgitta; Korsholm, Lars; Eika, Berit

    2011-11-01

    Very few studies have reported on the effect of admission tests on medical school dropout. The main aim of this study was to evaluate the predictive validity of non-grade-based admission testing versus grade-based admission relative to subsequent dropout. This prospective cohort study followed six cohorts of medical students admitted to the medical school at the University of Southern Denmark during 2002-2007 (n=1544). Half of the students were admitted based on their prior achievement of highest grades (Strategy 1) and the other half took a composite non-grade-based admission test (Strategy 2). Educational as well as social predictor variables (doctor-parent, origin, parenthood, parents living together, parent on benefit, university-educated parents) were also examined. The outcome of interest was students' dropout status at 2 years after admission. Multivariate logistic regression analysis was used to model dropout. Strategy 2 (admission test) students had a lower relative risk for dropping out of medical school within 2 years of admission (odds ratio 0.56, 95% confidence interval 0.39-0.80). Only the admission strategy, the type of qualifying examination and the priority given to the programme on the national application forms contributed significantly to the dropout model. Social variables did not predict dropout and neither did Strategy 2 admission test scores. Selection by admission testing appeared to have an independent, protective effect on dropout in this setting. © Blackwell Publishing Ltd 2011.

  3. Extreme Markup: The Fifty US Hospitals With The Highest Charge-To-Cost Ratios.

    Science.gov (United States)

    Bai, Ge; Anderson, Gerard F

    2015-06-01

    Using Medicare cost reports, we examined the fifty US hospitals with the highest charge-to-cost ratios in 2012. These hospitals have markups (ratios of charges over Medicare-allowable costs) approximately ten times their Medicare-allowable costs compared to a national average of 3.4 and a mode of 2.4. Analysis of the fifty hospitals showed that forty-nine are for profit (98 percent), forty-six are owned by for-profit hospital systems (92 percent), and twenty (40 percent) operate in Florida. One for-profit hospital system owns half of these fifty hospitals. While most public and private health insurers do not use hospital charges to set their payment rates, uninsured patients are commonly asked to pay the full charges, and out-of-network patients and casualty and workers' compensation insurers are often expected to pay a large portion of the full charges. Because it is difficult for patients to compare prices, market forces fail to constrain hospital charges. Federal and state governments may want to consider limitations on the charge-to-cost ratio, some form of all-payer rate setting, or mandated price disclosure to regulate hospital markups. Project HOPE—The People-to-People Health Foundation, Inc.

  4. Towards highest peak intensities for ultra-short MeV-range ion bunches

    Science.gov (United States)

    Busold, Simon; Schumacher, Dennis; Brabetz, Christian; Jahn, Diana; Kroll, Florian; Deppert, Oliver; Schramm, Ulrich; Cowan, Thomas E.; Blažević, Abel; Bagnoud, Vincent; Roth, Markus

    2015-07-01

    A laser-driven, multi-MeV-range ion beamline has been installed at the GSI Helmholtz center for heavy ion research. The high-power laser PHELIX drives the very short (picosecond) ion acceleration on μm scale, with energies ranging up to 28.4 MeV for protons in a continuous spectrum. The necessary beam shaping behind the source is accomplished by applying magnetic ion lenses like solenoids and quadrupoles and a radiofrequency cavity. Based on the unique beam properties from the laser-driven source, high-current single bunches could be produced and characterized in a recent experiment: At a central energy of 7.8 MeV, up to 5 × 108 protons could be re-focused in time to a FWHM bunch length of τ = (462 ± 40) ps via phase focusing. The bunches show a moderate energy spread between 10% and 15% (ΔE/E0 at FWHM) and are available at 6 m distance to the source und thus separated from the harsh laser-matter interaction environment. These successful experiments represent the basis for developing novel laser-driven ion beamlines and accessing highest peak intensities for ultra-short MeV-range ion bunches.

  5. Highest-order optical phonon-mediated relaxation in CdTe/ZnTe quantum dots

    International Nuclear Information System (INIS)

    Masumoto, Yasuaki; Nomura, Mitsuhiro; Okuno, Tsuyoshi; Terai, Yoshikazu; Kuroda, Shinji; Takita, K.

    2003-01-01

    The highest 19th-order longitudinal optical (LO) phonon-mediated relaxation was observed in photoluminescence excitation spectra of CdTe self-assembled quantum dots grown in ZnTe. Hot excitons photoexcited highly in the ZnTe barrier layer are relaxed into the wetting-layer state by emitting multiple LO phonons of the barrier layer successively. Below the wetting-layer state, the LO phonons involved in the relaxation are transformed to those of interfacial Zn x Cd 1-x Te surrounding CdTe quantum dots. The ZnTe-like and CdTe-like LO phonons of Zn x Cd 1-x Te and lastly acoustic phonons are emitted in the relaxation into the CdTe dots. The observed main relaxation is the fast relaxation directly into CdTe quantum dots and is not the relaxation through either the wetting-layer quantum well or the band bottom of the ZnTe barrier layer. This observation shows very efficient optical phonon-mediated relaxation of hot excitons excited highly in the ZnTe conduction band through not only the ZnTe extended state but also localized state in the CdTe quantum dots reflecting strong exciton-LO phonon interaction of telluride compounds

  6. Which Environmental Factors Have the Highest Impact on the Performance of People Experiencing Difficulties in Capacity?

    Directory of Open Access Journals (Sweden)

    Verena Loidl

    2016-04-01

    Full Text Available Disability is understood by the World Health Organization (WHO as the outcome of the interaction between a health condition and personal and environmental factors. Comprehensive data about environmental factors is therefore essential to understand and influence disability. We aimed to identify which environmental factors have the highest impact on the performance of people with mild, moderate and severe difficulties in capacity, who are at risk of experiencing disability to different extents, using data from a pilot study of the WHO Model Disability Survey in Cambodia and random forest regression. Hindering or facilitating aspects of places to socialize in community activities, transportation and natural environment as well as use and need of personal assistance and use of medication on a regular basis were the most important environmental factors across groups. Hindering or facilitating aspects of the general environment were the most relevant in persons experiencing mild levels of difficulties in capacity, while social support, attitudes of others and use of medication on a regular basis were highly relevant for the performance of persons experiencing moderate to higher levels of difficulties in capacity. Additionally, we corroborate the high importance of the use and need of assistive devices for people with severe difficulties in capacity.

  7. Drug Facts

    Medline Plus

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

  8. Drug Allergy

    Science.gov (United States)

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

  9. Entry time effects and follow-on drug competition.

    Science.gov (United States)

    Andrade, Luiz Flavio; Sermet, Catherine; Pichetti, Sylvain

    2016-01-01

    Pharmaceutical firms have been criticized for concentrating efforts of R&D on the so-called me-too or follow-on drugs. There have been many comments for and against the dissemination of these incremental innovations but few papers have broached the subject from an econometric point of view, possibly because identification of me-too or follow-on drugs is not so obvious. This paper focuses on the impact of entry order on follow-on drug competition in the French market between the years 2001 and 2007. More precisely, this study examines the effects on market share of first entrants in the follow-on drug market and how this possible competitive advantage changes over time. First results are coherent with theoretical microeconomic issues concerning the importance of being first. We find evidence that first movers in the follow-on drug market have the ability to capture and maintain greater market share for a long period of time. The hierarchical market position of follow-on drugs does not seem to be affected by generic drug emergence. From a dynamic perspective, our analysis shows that market share is positively correlated with the ability of follow-on drugs to set prices higher than the average follow-on drug prices in a specific therapeutic class, which means that market power remains considerably important for first movers. Moreover, we found that the optimum level of innovation to maximize market share is the highest one.

  10. Information ranks highest: Expectations of female adolescents with a rare genital malformation towards health care services.

    Directory of Open Access Journals (Sweden)

    Elisabeth Simoes

    Full Text Available Access to highly specialized health care services and support to meet the patient's specific needs is critical for health outcome, especially during age-related transitions within the health care system such as with adolescents entering adult medicine. Being affected by an orphan disease complicates the situation in several important respects. Long distances to dedicated institutions and scarcity of knowledge, even among medical doctors, may present major obstacles for proper access to health care services and health chances. This study is part of the BMBF funded TransCareO project examining in a mixed-method design health care provisional deficits, preferences, and barriers in health care access as perceived by female adolescents affected by the Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS, a rare (orphan genital malformation.Prior to a communicative validation workshop, critical elements of MRKHS related care and support (items were identified in interviews with MRKHS patients. During the subsequent workshop, 87 persons involved in health care and support for MRKHS were asked to rate the items using a 7-point Likert scale (7, strongly agree; 1, strongly disagree as to 1 the elements' potential importance (i.e., health care expected to be "best practice", or priority and 2 the presently experienced care. A gap score between the two was computed highlighting fields of action. Items were arranged into ten separate questionnaires representing domains of care and support (e.g., online-portal, patient participation. Within each domain, several items addressed various aspects of "information" and "access". Here, we present the outcome of items' evaluation by patients (attended, NPAT = 35; respondents, NRESP = 19.Highest priority scores occurred for domains "Online-Portal", "Patient participation", and "Tailored informational offers", characterizing them as extremely important for the perception as best practice. Highest gap scores yielded domains

  11. A New Orally Active, Aminothiol Radioprotector-Free of Nausea and Hypotension Side Effects at Its Highest Radioprotective Doses

    Energy Technology Data Exchange (ETDEWEB)

    Soref, Cheryl M. [ProCertus BioPharm, Inc., Madison, WI (United States); Hacker, Timothy A. [Department of Medicine, Cardiovascular Physiology Core, University of Wisconsin-Madison, Madison, WI (United States); Fahl, William E., E-mail: fahl@oncology.wisc.edu [ProCertus BioPharm, Inc., Madison, WI (United States); McArdle Laboratory for Cancer Research, University of Wisconsin Carbone Cancer Center, Madison, WI (United States)

    2012-04-01

    Purpose: A new aminothiol, PrC-210, was tested for orally conferred radioprotection (rats, mice; 9.0 Gy whole-body, which was otherwise lethal to 100% of the animals) and presence of the debilitating side effects (nausea/vomiting, hypotension/fainting) that restrict use of the current aminothiol, amifostine (Ethyol, WR-2721). Methods and Materials: PrC-210 in water was administered to rats and mice at times before irradiation, and percent-survival was recorded for 60 days. Subcutaneous (SC) amifostine (positive control) or SC PrC-210 was administered to ferrets (Mustela putorius furo) and retching/emesis responses were recorded. Intraperitoneal amifostine (positive control) or PrC-210 was administered to arterial cannulated rats to score drug-induced hypotension. Results: Oral PrC-210 conferred 100% survival in rat and mouse models against an otherwise 100% lethal whole-body radiation dose (9.0 Gy). Oral PrC-210, administered by gavage 30-90 min before irradiation, conferred a broad window of radioprotection. The comparison of PrC-210 and amifostine side effects was striking because there was no retching or emesis in 10 ferrets treated with PrC-210 and no induced hypotension in arterial cannulated rats treated with PrC-210. The tested PrC-210 doses were the ferret and rat equivalent doses of the 0.5 maximum tolerated dose (MTD) PrC-210 dose in mice. The human equivalent of this mouse 0.5 MTD PrC-210 dose would likely be the highest PrC-210 dose used in humans. By comparison, the mouse 0.5 MTD amifostine dose, 400 {mu}g/g body weight (equivalent to the human amifostine dose of 910 mg/m{sup 2}), when tested at equivalent ferret and rat doses in the above models produced 100% retching/vomiting in ferrets and 100% incidence of significant, progressive hypotension in rats. Conclusions: The PrC-210 aminothiol, with no detectable nausea/vomiting or hypotension side effects in these preclinical models, is a logical candidate for human drug development to use in healthy

  12. Nonlinear Analysis to Detect if Excellent Nursing Work Environments Have Highest Well-Being.

    Science.gov (United States)

    Casalicchio, Giuseppe; Lesaffre, Emmanuel; Küchenhoff, Helmut; Bruyneel, Luk

    2017-09-01

    To detect potentially nonlinear associations between nurses' work environment and nurse staffing on the one hand and nurse burnout on the other hand. A cross-sectional multicountry study for which data collection using a survey of 33,731 registered nurses in 12 European countries took place during 2009 to 2010. A semiparametric latent variable model that describes both linear and potentially nonlinear associations between burnout (Maslach Burnout Inventory: emotional exhaustion, depersonalization, personal accomplishment) and work environment (Practice Environment Scale of the Nursing Work Index: managerial support for nursing, doctor-nurse collegial relations, promotion of care quality) and staffing (patient-to-nurse ratio). Similar conclusions are reached from linear and nonlinear models estimating the association between work environment and burnout. For staffing, an increase in the patient-to-nurse ratio is associated with an increase in emotional exhaustion. At about 15 patients per nurse, no further increase in emotional exhaustion is seen. Absence of evidence for diminishing returns of improving work environments suggests that continuous improvement and achieving excellence in nurse work environments pays off strongly in terms of lower nurse-reported burnout rates. Nurse staffing policy would benefit from a larger number of studies that identify specific minimum as well as maximum thresholds at which inputs affect nurse and patient outcomes. Nurse burnout is omnipresent and has previously been shown to be related to worse patient outcomes. Additional increments in characteristics of excellent work environments, up to the highest possible standard, correspond to lower nurse burnout. © 2017 Sigma Theta Tau International.

  13. Lost opportunities in HIV prevention: programmes miss places where exposures are highest

    Science.gov (United States)

    Sandøy, Ingvild F; Siziya, Seter; Fylkesnes, Knut

    2008-01-01

    Background Efforts at HIV prevention that focus on high risk places might be more effective and less stigmatizing than those targeting high risk groups. The objective of the present study was to assess risk behaviour patterns, signs of current preventive interventions and apparent gaps in places where the risk of HIV transmission is high and in communities with high HIV prevalence. Methods The PLACE method was used to collect data. Inhabitants of selected communities in Lusaka and Livingstone were interviewed about where people met new sexual partners. Signs of HIV preventive activities in these places were recorded. At selected venues, people were interviewed about their sexual behaviour. Peer educators and staff of NGOs were also interviewed. Results The places identified were mostly bars, restaurants or sherbeens, and fewer than 20% reported any HIV preventive activity such as meetings, pamphlets or posters. In 43% of places in Livingstone and 26% in Lusaka, condoms were never available. There were few active peer educators. Among the 432 persons in Lusaka and 676 in Livingstone who were invited for interview about sexual behaviour, consistent condom use was relatively high in Lusaka (77%) but low in Livingstone (44% of men and 34% of women). Having no condom available was the most common reason for not using one. Condom use in Livingstone was higher among individuals socializing in places where condoms always were available. Conclusion In the places studied we found a high prevalence of behaviours with a high potential for HIV transmission but few signs of HIV preventive interventions. Covering the gaps in prevention in these high exposure places should be given the highest priority. PMID:18218124

  14. How to identify the person holding the highest position in the criminal hierarchy?

    Directory of Open Access Journals (Sweden)

    Grigoryev D.A.

    2014-12-01

    Full Text Available The current version of the resolution of the RF Supreme Court Plenum of June 10, 2010 N 12, clarifying the provisions of the law on liability for crimes committed by a person holding the highest position in the criminal hierarchy (Part 4 of Article 210 of the RF Criminal Code, is criticized. Evaluative character of the considered aggravating circumstance doesn’t allow to develop clear criteria for identifying the leaders of the criminal environment. Basing on the theory provisions and court practice, the authors suggest three criteria. The first criterion is specific actions including: establishment and leadership of the criminal association (criminal organization; coordinating criminal acts; creating sustainable links between different organized groups acting independently; dividing spheres of criminal influence, sharing criminal income and other criminal activities, indicating person’s authority and leadership in a particular area or in a particular sphere of activity. The second is having money, valuables and other property obtained by criminal means, without the person’s direct participation in their acquisition; transferring money, valuables and other property to that person systematically, without legal grounds (unjust enrichment; spending that money, valuables and other property to carry out criminal activities (crimes themselves and conditions of their commission. The third is international criminal ties manifested in committing one of the crimes under Part 1 of Article 210 of the RF Criminal Code, if this crime is transnational in nature; ties with extremist and (or terrorist organizations, as well as corruption ties. The court may use one or several of these criteria.

  15. Analisa Penggunaan Tertinggi dan Terbaik (Highest and Best Use Analysis pada Lahan Pasar Turi Lama Surabaya

    Directory of Open Access Journals (Sweden)

    Maulida Herradiyanti

    2017-01-01

    Full Text Available Pasar  Turi  merupakan  pasar  yang  telah lama  menjadi  ikon  perdagangan  tidak  hanya  di Surabaya,  namun  juga  di  Indonesia  Timur.  Kebakaran hebat yang terjadi pada Juli 2007 telah menghanguskan bangunan Pasar Turi. Aktivitas perdagangan di tempat tersebut  otomatis  terhenti.  Hingga saat ini, lahan Pasar Turi  Tahap  III  atau  yang  biasa  disebut  Pasar  Turi Lama  masih  terbengkalai.  Padahal,  lahan  seluas  16281 m2tersebut terletak di wilayah sentra perdagangan dan cocok  untuk  dikembangkan  menjadi properti komersial seperti perkantoran, pertokoan, rumah toko (ruko, danpasar tradisional. Salah  satu  cara  untuk  menentukan  penggunaan lahan Pasar Turi Lama adalah dengan metode Highest and  Best  Use  (HBU.  HBU  adalah  suatu  metode  untuk menentukan  penggunaan  aset  yang  memberikan peruntukan  paling  optimal sehingga dapat memberikan nilai  lahan  tertinggi.  Kriteria  HBU  yaitu  diijinkan secara  legal,  memungkinkan  secara  fisik,  layak  secara finansial, dan memiliki produktivitas maksimum.Hasil penelitian ini didapatkan alternatif pertokoan sebagai  alternatif  penggunaan  lahan  terbaik  dengan nilai  lahan  tertinggi  yaitu  sebesar  Rp27.994.695,78/m2dengan produktivitas maksimum sebesar  124%.

  16. Risk of influenza transmission in a hospital emergency department during the week of highest incidence.

    Science.gov (United States)

    Esteve-Esteve, Miguel; Bautista-Rentero, Daniel; Zanón-Viguer, Vicente

    2018-02-01

    To estimate the risk of influenza transmission in patients coming to a hospital emergency department during the week of highest incidence and to analyze factors associated with transmission. Retrospective observational analysis of a cohort of patients treated in the emergency room during the 2014-2015 flu season. The following variables were collected from records: recorded influenza diagnosis, results of a rapid influenza confirmation test, point of exposure (emergency department, outpatient clinic, or the community), age, sex, flu vaccination or not, number of emergency visits, time spent in the waiting room, and total time in the hospital. We compiled descriptive statistics and performed bivariate and multivariate analyses by means of a Poisson regression to estimate relative risk (RR) and 95% CIs. The emergency department patients had a RR of contracting influenza 3.29 times that of the communityexposed population (95% CI, 1.53-7.08, P=.002); their risk was 2.05 times greater than that of outpatient clinic visitors (95% CI, 1.04-4.02, P=.036). Emergency patients under the age of 15 years had a 5.27 greater risk than older patients (95% CI, 1.59-17.51; P=.007). The RR of patients visiting more than once was 11.43 times greater (95% CI, 3.58-36.44; P<.001). The risk attributable to visiting the emergency department risk was 70.5%, whereas risk attributable to community exposure was 2%. The risk of contracting influenza is greater for emergency department patients than for the general population or for patients coming to the hospital for outpatient clinic visits. Patients under the age of 15 years incur greater risk.

  17. Trace elements in natural drugs determined by INAA

    International Nuclear Information System (INIS)

    Chen Kehshaw; Tseng Chialiang; Lin Tehsien

    1993-01-01

    Natural drugs are widely used for diuretic, phlegm elimination and stomach invigoration purposes. Seventy-five of the most common remedies used by Chinese people have been subjected to trace element survey analysis by instrumental neutron activation. Within this large number of different natural products, fourteen trace elements (K, Sc, Cr, Fe, Co, Zn, Br, Rb, Cs, La, Sm, Eu, Au and Th) are commonly detected. Among these elements, Fe had the highest concentration followed by Zn, and Rb, Sm, Eu and Au were found to have the lowest concentrations. Although the three groups of natural drugs exhibit a widely different therapeutic action, the concentration ranges of the fourteen elements were very similar. While this suggests no apparent specific role for the trace elements in the drug function, parallels are drawn between the known drug related functions of Rb, Zn, Br, Fe, Co and K and the levels of elements found in the natural drugs. It is concluded that the various natural drugs also provide human benefits through supplements of essential elements such as Fe, Zn, Cr, Sc, Rb and Co. (author) 13 refs.; 5 tabs

  18. Drugs in breast milk.

    Science.gov (United States)

    Hervada, A R; Feit, E; Sagraves, R

    1978-09-01

    The amount of drug excreted into breast milk is dependent upon the lipid solubility of the medication, the mechanism of transport, the degree of ionization, and change in plasma pH. The higher the lipid solubility, the greater the concentration in human milk. The majority of drugs are transported into mammary blood capillaries by passive diffusion. The rest are transported by reverse pinocytosis. Once the drug has entered the epithelial cells of breast tissue, the drug molecules are excreted into the human milk by active transport, passive diffusion, or apocrine secretion. The amount of free (active) drug available for transport depends on the degree of protein binding the plasma pH. Another factor affecting excretion of drugs is the time when breast feeding occurs. In the 1st few days of life, when colostrum is present, water-soluble drugs pass through the breast more easily than afterwards when milk is produced. Then lipid-soluble drugs cross in higher concentrations. The effect on nursing infants is dependent on the amount excreted into the milk, the total amount absorbed by the infant, and the toxicity of the drug. The use of the following drugs in breast feeding mothers is reviewed: anticoagulants, antihypertensives and diuretics, antimicrobials, drugs affecting the central nervous system (alcohol, chloral hydrate, meprobamate, lithium, and aspirin), marijuana, other drugs (antihistamines, atropine, ergot alkaloids, laxatives, nicotine, iodides, propylthiouracil, theophylline), hormones (insulin, thyroxine, and oral contraceptives), and radiopharmaceuticals.

  19. Drug-Target Kinetics in Drug Discovery.

    Science.gov (United States)

    Tonge, Peter J

    2018-01-17

    The development of therapies for the treatment of neurological cancer faces a number of major challenges including the synthesis of small molecule agents that can penetrate the blood-brain barrier (BBB). Given the likelihood that in many cases drug exposure will be lower in the CNS than in systemic circulation, it follows that strategies should be employed that can sustain target engagement at low drug concentration. Time dependent target occupancy is a function of both the drug and target concentration as well as the thermodynamic and kinetic parameters that describe the binding reaction coordinate, and sustained target occupancy can be achieved through structural modifications that increase target (re)binding and/or that decrease the rate of drug dissociation. The discovery and deployment of compounds with optimized kinetic effects requires information on the structure-kinetic relationships that modulate the kinetics of binding, and the molecular factors that control the translation of drug-target kinetics to time-dependent drug activity in the disease state. This Review first introduces the potential benefits of drug-target kinetics, such as the ability to delineate both thermodynamic and kinetic selectivity, and then describes factors, such as target vulnerability, that impact the utility of kinetic selectivity. The Review concludes with a description of a mechanistic PK/PD model that integrates drug-target kinetics into predictions of drug activity.

  20. Concentrated Ownership

    DEFF Research Database (Denmark)

    Rose, Caspar

    2014-01-01

    This entry summarizes the main theoretical contributions and empirical findings in relation to concentrated ownership from a law and economics perspective. The various forms of concentrated ownership are described as well as analyzed from the perspective of the legal protection of investors......, especially minority shareholders. Concentrated ownership is associated with benefits and costs. Concentrated ownership may reduce agency costs by increased monitoring of top management. However, concentrated ownership may also provide dominating owners with private benefits of control....

  1. Highest Plasma Phenylalanine Levels in (Very Premature Infants on Intravenous Feeding; A Need for Concern.

    Directory of Open Access Journals (Sweden)

    Ernesto Cortés-Castell

    Full Text Available To analyse the association in newborns between blood levels of phenylalanine and feeding method and gestational age.This observational, cross-sectional study included a sample of 11,829 infants between 2008 and 2013 in a Spanish region. Data were recorded on phenylalanine values, feeding method [breast, formula, mixed (breast plus formula, or partial or fully intravenous feeding], gestational age in weeks (<32, 32-37, ≥37, gender and days since birth at the moment of blood collection. Outcomes were [phenylalanine] and [phenylalanine] ≥95th percentile. Associations were analysed using multivariate models [linear (means difference and logistic regression (adjusted odds ratios].Higher phenylalanine values were associated with lower gestational age (p<0.001 and with intravenous feeding (p<0.001.The degree of prematurity and intravenous feeding influenced the plasma concentration of phenylalanine in the newborn. Caution should be taken in [phenylalanine] for newborns with intravenous feeding, monitoring them carefully. Very preterm infants given the recommended amount of amino acids should also be strictly monitored. These findings should be taken into consideration and call for adapting the amounts to the needs of the infant.

  2. Consumer Airfare Report: Table 5 - Detailed Fare Information For Highest and Lowest Fare Markets Under 750 Miles

    Data.gov (United States)

    Department of Transportation — Provides detailed fare information for highest and lowest fare markets under 750 miles. For a more complete explanation, please read the introductory information at...

  3. Illicit drugs in Canadian municipal wastewater and estimates of community drug use

    Energy Technology Data Exchange (ETDEWEB)

    Metcalfe, Chris, E-mail: cmetcalfe@trentu.c [Worsfold Water Quality Centre, Trent University, 1600 West Bank Drive Peterborough, ON, K9J 7B8 (Canada); Tindale, Kathryn [Worsfold Water Quality Centre, Trent University, 1600 West Bank Drive Peterborough, ON, K9J 7B8 (Canada); Li, Hongxia, E-mail: lihongxia@trentu.c [Worsfold Water Quality Centre, Trent University, 1600 West Bank Drive Peterborough, ON, K9J 7B8 (Canada); Rodayan, Angela [Department of Chemical Engineering, McGill University, 3610 University St., Montreal, QC, H3A 2B2 (Canada); Yargeau, Viviane, E-mail: viviane.yargeau@mcgill.c [Department of Chemical Engineering, McGill University, 3610 University St., Montreal, QC, H3A 2B2 (Canada)

    2010-10-15

    In this study of wastewater treatment plants in three Canadian cities, selected illicit drugs, including cocaine and its major metabolite, benzoylecgonine (BE), amphetamine, methamphetamine and ecstasy (i.e. MDMA) were detected in untreated wastewater. Cocaine was the most widely used illicit drug at a median level for the 3 cities of 15.7 doses per day per 1000 people. For the other drugs, the median doses per day per 1000 people were 1.8 for amphetamine, 4.5 for methamphetamine and 0.4 for ecstasy. Methamphetamine use was highest in the largest city and cocaine use was lowest in the smallest city. Removal of the illicit drugs by wastewater treatment was generally >50%, except in a WWTP that uses primary treatment. The community consumption estimate for ecstasy in the present study is far below published estimates of the prevalence of ecstasy use among the Canadian population, which may be due to only occasional use of ecstasy. - Cocaine and amphetamines were detected in untreated and treated sewage in the wastewater treatment plants of three Canadian cities, and community consumption patterns estimated from the concentrations of the drugs in untreated wastewater were consistent with estimates of the use of illicit drugs in Canada.

  4. Illicit drugs in Canadian municipal wastewater and estimates of community drug use

    International Nuclear Information System (INIS)

    Metcalfe, Chris; Tindale, Kathryn; Li, Hongxia; Rodayan, Angela; Yargeau, Viviane

    2010-01-01

    In this study of wastewater treatment plants in three Canadian cities, selected illicit drugs, including cocaine and its major metabolite, benzoylecgonine (BE), amphetamine, methamphetamine and ecstasy (i.e. MDMA) were detected in untreated wastewater. Cocaine was the most widely used illicit drug at a median level for the 3 cities of 15.7 doses per day per 1000 people. For the other drugs, the median doses per day per 1000 people were 1.8 for amphetamine, 4.5 for methamphetamine and 0.4 for ecstasy. Methamphetamine use was highest in the largest city and cocaine use was lowest in the smallest city. Removal of the illicit drugs by wastewater treatment was generally >50%, except in a WWTP that uses primary treatment. The community consumption estimate for ecstasy in the present study is far below published estimates of the prevalence of ecstasy use among the Canadian population, which may be due to only occasional use of ecstasy. - Cocaine and amphetamines were detected in untreated and treated sewage in the wastewater treatment plants of three Canadian cities, and community consumption patterns estimated from the concentrations of the drugs in untreated wastewater were consistent with estimates of the use of illicit drugs in Canada.

  5. Elliptical concentrators.

    Science.gov (United States)

    Garcia-Botella, Angel; Fernandez-Balbuena, Antonio Alvarez; Bernabeu, Eusebio

    2006-10-10

    Nonimaging optics is a field devoted to the design of optical components for applications such as solar concentration or illumination. In this field, many different techniques have been used to produce optical devices, including the use of reflective and refractive components or inverse engineering techniques. However, many of these optical components are based on translational symmetries, rotational symmetries, or free-form surfaces. We study a new family of nonimaging concentrators called elliptical concentrators. This new family of concentrators provides new capabilities and can have different configurations, either homofocal or nonhomofocal. Translational and rotational concentrators can be considered as particular cases of elliptical concentrators.

  6. The antioxidant level of Alaska's wild berries: high, higher and highest

    Directory of Open Access Journals (Sweden)

    Roxie Rodgers Dinstel

    2013-08-01

    . Alaska wild berries have extraordinarily high antioxidant levels. Though cooking lowered the antioxidant level, and adding ingredients such as sugar diluted the antioxidant concentration, products made from berries are high sources of antioxidants.

  7. Mercury contamination from artisanal gold mining in Antioquia, Colombia: The world's highest per capita mercury pollution.

    Science.gov (United States)

    Cordy, Paul; Veiga, Marcello M; Salih, Ibrahim; Al-Saadi, Sari; Console, Stephanie; Garcia, Oseas; Mesa, Luis Alberto; Velásquez-López, Patricio C; Roeser, Monika

    2011-12-01

    The artisanal gold mining sector in Colombia has 200,000 miners officially producing 30tonnes Au/a. In the Northeast of the Department of Antioquia, there are 17 mining towns and between 15,000 and 30,000 artisanal gold miners. Guerrillas and paramilitary activities in the rural areas of Antioquia pushed miners to bring their gold ores to the towns to be processed in Processing Centers or entables. These Centers operate in the urban areas amalgamating the whole ore, i.e. without previous concentration, and later burn gold amalgam without any filtering/condensing system. Based on mercury mass balance in 15 entables, 50% of the mercury added to small ball mills (cocos) is lost: 46% with tailings and 4% when amalgam is burned. In just 5 cities of Antioquia, with a total of 150,000 inhabitants: Segovia, Remedios, Zaragoza, El Bagre, and Nechí, there are 323 entables producing 10-20tonnes Au/a. Considering the average levels of mercury consumption estimated by mass balance and interviews of entables owners, the mercury consumed (and lost) in these 5 municipalities must be around 93tonnes/a. Urban air mercury levels range from 300ng Hg/m(3) (background) to 1million ng Hg/m(3) (inside gold shops) with 10,000ng Hg/m(3) being common in residential areas. The WHO limit for public exposure is 1000ng/m(3). The total mercury release/emissions to the Colombian environment can be as high as 150tonnes/a giving this country the shameful first position as the world's largest mercury polluter per capita from artisanal gold mining. One necessary government intervention is to cut the supply of mercury to the entables. In 2009, eleven companies in Colombia legally imported 130tonnes of metallic mercury, much of it flowing to artisanal gold mines. Entables must be removed from urban centers and technical assistance is badly needed to improve their technology and reduce emissions. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Drug Safety

    Science.gov (United States)

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

  9. Drug Abuse

    Science.gov (United States)

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

  10. Drug Facts

    Medline Plus

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

  11. Drug Facts

    Medline Plus

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

  12. Club Drugs

    Science.gov (United States)

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

  13. Concentration risk

    Directory of Open Access Journals (Sweden)

    Matić Vesna

    2016-01-01

    Full Text Available Concentration risk has been gaining a special dimension in the contemporary financial and economic environment. Financial institutions are exposed to this risk mainly in the field of lending, mostly through their credit activities and concentration of credit portfolios. This refers to the concentration of different exposures within a single risk category (credit risk, market risk, operational risk, liquidity risk.

  14. Concentrator Photovoltaics

    CERN Document Server

    Luque, Antonio L

    2007-01-01

    Photovoltaic solar-energy conversion is one of the most promising technologies for generating renewable energy, and conversion of concentrated sunlight can lead to reduced cost for solar electricity. In fact, photovoltaic conversion of concentrated sunlight insures an efficient and cost-effective sustainable power resource. This book gives an overview of all components, e.g. cells, concentrators, modules and systems, for systems of concentrator photovoltaics. The authors report on significant results related to design, technology, and applications, and also cover the fundamental physics and market considerations. Specific contributions include: theory and practice of sunlight concentrators; an overview of concentrator PV activities; a description of concentrator solar cells; design and technology of modules and systems; manufacturing aspects; and a market study.

  15. Highest weight generating functions for hyperKähler T{sup ⋆}(G/H) spaces

    Energy Technology Data Exchange (ETDEWEB)

    Hanany, Amihay [Theoretical Physics Group, Imperial College London,Prince Consort Road, London, SW7 2AZ (United Kingdom); Ramgoolam, Sanjaye [Centre for Research in String Theory,School of Physics and Astronomy, Queen Mary University of London,Mile End Road, London E1 4NS (United Kingdom); Rodriguez-Gomez, Diego [Department of Physics, Universidad de Oviedo,Avda. Calvo Sotelo 18, 33007, Oviedo (Spain)

    2016-10-05

    We develop an efficient procedure for counting holomorphic functions on a hyperKahler cone that has a resolution as a cotangent bundle of a homogeneous space by providing a formula for computing the corresponding Highest Weight Generating function.

  16. Influence of sports games classes in specialized sections on formation of healthy lifestyle at students of the highest educational institutions

    OpenAIRE

    Kudryavtsev, M.; Galimova, A.; Alshuvayli, Kh.; Altuvayni, A.

    2018-01-01

    In modern society, the problem of formation of healthy lifestyle at youth, in particular, at students of the highest educational institutions is very relevant. Sport is a good mean for motivation, in this case – sports games. Purpose: to reveal consequences of participation in sports games and influence of these actions on healthy lifestyle of students of the highest educational institutions, to designate a role of classes in the sections, specializing in preparation for sports games in this ...

  17. The part of the solar spectrum with the highest influence on the formation of SOA in the continental boundary layer

    Directory of Open Access Journals (Sweden)

    M. Boy

    2002-01-01

    Full Text Available The relationship between nucleation events and spectral solar irradiance was analysed using two years of data collected at the Station for Measuring Forest Ecosystem-Atmosphere Relations (SMEAR II in Hyytiälä, Finland. We analysed the data in two different ways. In the first step we calculated ten nanometer average values from the irradiance measurements between 280 and 580 nm and explored if any special wavelengths groups showed higher values on event days compared to a spectral reference curve for all the days for 2 years or to reference curves for every month. The results indicated that short wavelength irradiance between 300 and 340 nm is higher on event days in winter (February and March compared to the monthly reference graph but quantitative much smaller than in spring or summer. By building the ratio between the average values of different event classes and the yearly reference graph we obtained peaks between 1.17 and 1.6 in the short wavelength range (300--340 nm. In the next step we included number concentrations of particles between 3 and 10 nm and calculated correlation coefficients between the different wavelengths groups and the particles. The results were quite similar to those obtained previously; the highest correlation coefficients were reached for the spectral irradiance groups 3--5 (300--330 nm with average values for the single event classes around 0.6 and a nearly linear decrease towards higher wavelengths groups by 30%. Both analyses indicate quite clearly that short wavelength irradiance between 300 and 330 or 340 nm is the most important solar spectral radiation for the formation of newly formed aerosols. In the end we introduce a photochemical mechanism as one possible pathway how short wavelength irradiance can influence the formation of SOA by calculating the production rate of excited oxygen. This mechanism shows in which way short wavelength irradiance can influence the formation of new particles even though the

  18. Discontinued drugs in 2012: cardiovascular drugs.

    Science.gov (United States)

    Zhao, Hong-Ping; Jiang, Hong-Min; Xiang, Bing-Ren

    2013-11-01

    The continued high rate of cardiovascular morbidity and mortality has attracted wide concern and great attention of pharmaceutical industry. In order to reduce the attrition of cardiovascular drug R&D, it might be helpful recapitulating previous failures and identifying the potential factors to success. This perspective mainly analyses the 30 cardiovascular drugs dropped from clinical development in 2012. Reasons causing the termination of the cardiovascular drugs in the past 5 years are also tabulated and analysed. The analysis shows that the attrition is highest in Phase II trials and financial and strategic factors and lack of clinical efficacy are the principal reasons for these disappointments. To solve the four problems (The 'better than the Beatles' problem, the 'cautious regulator' problem, the 'throw money at it' tendency and the 'basic researchbrute force' bias) is recommended as the main measure to increase the number and quality of approvable products.

  19. Drug allergies

    Science.gov (United States)

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

  20. Study Drugs

    Science.gov (United States)

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

  1. Drug Facts

    Medline Plus

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

  2. Drug Facts

    Medline Plus

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

  3. Drug Reactions

    Science.gov (United States)

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

  4. Drug Facts

    Science.gov (United States)

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

  5. Concentrating Radioactivity

    Science.gov (United States)

    Herrmann, Richard A.

    1974-01-01

    By concentrating radioactivity contained on luminous dials, a teacher can make a high reading source for classroom experiments on radiation. The preparation of the source and its uses are described. (DT)

  6. Grapefruit and drug interactions.

    Science.gov (United States)

    2012-12-01

    Since the late 1980s, grapefruit juice has been known to affect the metabolism of certain drugs. Several serious adverse effects involving drug interactions with grapefruit juice have been published in detail. The components of grapefruit juice vary considerably depending on the variety, maturity and origin of the fruit, local climatic conditions, and the manufacturing process. No single component accounts for all observed interactions. Other grapefruit products are also occasionally implicated, including preserves, lyophylised grapefruit juice, powdered whole grapefruit, grapefruit seed extract, and zest. Clinical reports of drug interactions with grapefruit juice are supported by pharmacokinetic studies, each usually involving about 10 healthy volunteers, in which the probable clinical consequences were extrapolated from the observed plasma concentrations. Grapefruit juice inhibits CYP3A4, the cytochrome P450 isoenzyme most often involved in drug metabolism. This increases plasma concentrations of the drugs concerned, creating a risk of overdose and dose-dependent adverse effects. Grapefruit juice also inhibits several other cytochrome P450 isoenzymes, but they are less frequently implicated in interactions with clinical consequences. Drugs interacting with grapefruit and inducing serious clinical consequences (confirmed or very probable) include: immunosuppressants, some statins, benzodiazepines, most calcium channel blockers, indinavir and carbamazepine. There are large inter-individual differences in enzyme efficiency. Along with the variable composition of grapefruit juice, this makes it difficult to predict the magnitude and clinical consequences of drug interactions with grapefruit juice in a given patient. There is increasing evidence that transporter proteins such as organic anion transporters and P-glycoprotein are involved in interactions between drugs and grapefruit juice. In practice, numerous drugs interact with grapefruit juice. Although only a few

  7. Highest PBDE levels (max 63 ppm) yet found in biota measured in seabird eggs from San Francisco Bay

    Energy Technology Data Exchange (ETDEWEB)

    She, J.; Holden, A.; Tanner, M.; Sharp, M.; Hooper, K. [Department of Toxic Substances Control, Berkeley, CA (United States). Hazardous Materials Lab.; Adelsbach, T. [Environmental Contaminants Division, Sacramento Fish and Wildlife Office, US Fish and Wildlife Service, Sacramento, CA (United States)

    2004-09-15

    High levels of polybrominated diphenylethers (PBDEs) have been found in humans and wildlife from the San Francisco Bay Area, with levels in women among the highest in the world, and levels in piscivorous seabird eggs at the ppm level. Seabirds are useful for monitoring and assessing ecosystem health at various times and places because they occupy a high trophic level in the marine food web, are long-lived, and are generally localized near their breeding and non-breeding sites. In collaboration with the US Fish and Wildlife Services (USFWS), we are carrying out a three-year investigation of dioxin, PCB and PBDE levels in eggs from fish-eating seabirds. Year 1 (2002) PBDE measurements from 73 bird eggs were reported at Dioxin2003. Year 2 (2003) PBDE measurements from 45 samples are presented in this report. The highest PBDE level measured in eggs was 63 ppm, lipid, which is the highest PBDE level, yet reported in biota.

  8. A REVIEW ON OSMOTIC DRUG DELIVERY SYSTEM

    OpenAIRE

    Harnish Patel; Upendra Patel; Hiren Kadikar; Bhavin Bhimani; Dhiren Daslaniya; Ghanshyam Patel

    2012-01-01

    Conventional oral drug delivery systems supply an instantaneous release of drug, which cannot control the release of the drug and effective concentration at the target site. This kind of dosing pattern may result in constantly changing, unpredictable plasma concentrations. Drugs can be delivered in a controlled pattern over a long period of time by the process of osmosis. Osmotic devices are the most promising strategy based systems for controlled drug delivery. They are the most reliable con...

  9. Inclusion of Highest Glasgow Coma Scale Motor Component Score in Mortality Risk Adjustment for Benchmarking of Trauma Center Performance.

    Science.gov (United States)

    Gomez, David; Byrne, James P; Alali, Aziz S; Xiong, Wei; Hoeft, Chris; Neal, Melanie; Subacius, Harris; Nathens, Avery B

    2017-12-01

    The Glasgow Coma Scale (GCS) is the most widely used measure of traumatic brain injury (TBI) severity. Currently, the arrival GCS motor component (mGCS) score is used in risk-adjustment models for external benchmarking of mortality. However, there is evidence that the highest mGCS score in the first 24 hours after injury might be a better predictor of death. Our objective was to evaluate the impact of including the highest mGCS score on the performance of risk-adjustment models and subsequent external benchmarking results. Data were derived from the Trauma Quality Improvement Program analytic dataset (January 2014 through March 2015) and were limited to the severe TBI cohort (16 years or older, isolated head injury, GCS ≤8). Risk-adjustment models were created that varied in the mGCS covariates only (initial score, highest score, or both initial and highest mGCS scores). Model performance and fit, as well as external benchmarking results, were compared. There were 6,553 patients with severe TBI across 231 trauma centers included. Initial and highest mGCS scores were different in 47% of patients (n = 3,097). Model performance and fit improved when both initial and highest mGCS scores were included, as evidenced by improved C-statistic, Akaike Information Criterion, and adjusted R-squared values. Three-quarters of centers changed their adjusted odds ratio decile, 2.6% of centers changed outlier status, and 45% of centers exhibited a ≥0.5-SD change in the odds ratio of death after including highest mGCS score in the model. This study supports the concept that additional clinical information has the potential to not only improve the performance of current risk-adjustment models, but can also have a meaningful impact on external benchmarking strategies. Highest mGCS score is a good potential candidate for inclusion in additional models. Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  10. Vaginal drug distribution modeling.

    Science.gov (United States)

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

    2015-09-15

    This review presents and applies fundamental mass transport theory describing the diffusion and convection driven mass transport of drugs to the vaginal environment. It considers sources of variability in the predictions of the models. It illustrates use of model predictions of microbicide drug concentration distribution (pharmacokinetics) to gain insights about drug effectiveness in preventing HIV infection (pharmacodynamics). The modeling compares vaginal drug distributions after different gel dosage regimens, and it evaluates consequences of changes in gel viscosity due to aging. It compares vaginal mucosal concentration distributions of drugs delivered by gels vs. intravaginal rings. Finally, the modeling approach is used to compare vaginal drug distributions across species with differing vaginal dimensions. Deterministic models of drug mass transport into and throughout the vaginal environment can provide critical insights about the mechanisms and determinants of such transport. This knowledge, and the methodology that obtains it, can be applied and translated to multiple applications, involving the scientific underpinnings of vaginal drug distribution and the performance evaluation and design of products, and their dosage regimens, that achieve it. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Dominant psychoactive drugs in the Central European region: A wastewater study.

    Science.gov (United States)

    Mackuľak, Tomáš; Bodík, Igor; Hasan, Jamal; Grabic, Roman; Golovko, Oksana; Vojs-Staňová, Andrea; Gál, Miroslav; Naumowicz, Monika; Tichý, Jozef; Brandeburová, Paula; Híveš, Ján

    2016-10-01

    The aim of this study was to analyze 26 various illicit drugs, psychopharmaceuticals and metabolites thereof in sewer from 17 selected wastewater treatment plants (WWTPs) in the Slovak and Czech Republics. Urinary bio-markers used were analyzed using liquid chromatography coupled with the tandem mass spectrometry (LC-MS/MS). We then compared our results with data obtained in other parts of Europe and the world. The present study shows that the Slovak and Czech Republics have one of the highest methamphetamine consumption rates in Europe. Within Slovakia, the highest level of methamphetamine consumption was found in Dunajská Streda with the mean specific load of the drug in sewage being up to 479mg/day/1000 inhabitants; the next highest load was detected in Trnava (354mg/day/1000 inhabitants). The methamphetamine, ecstasy and cannabis consumptions in our study were comparable to those found in other European cities, whereas cocaine consumption was lower. Among all of the studied psychopharmaceuticals, tramadol and venlafaxine were represented in the highest concentrations. The highest mean specific load of tramadol was detected in the spa town of Piešťany (371mg/day/1000 inhabitants) and Košice (372mg/day/1000 inhabitants), while the highest mean loads of venlafaxine were recorded for the towns of Trenčín (230mg/day/1000 inhabitants) and Piešťany (108mg/day/1000 inhabitants). Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Role of drug transporters and drug accumulation in the temporal acquisition of drug resistance

    International Nuclear Information System (INIS)

    Hembruff, Stacey L; Laberge, Monique L; Villeneuve, David J; Guo, Baoqing; Veitch, Zachary; Cecchetto, Melanie; Parissenti, Amadeo M

    2008-01-01

    Anthracyclines and taxanes are commonly used in the treatment of breast cancer. However, tumor resistance to these drugs often develops, possibly due to overexpression of drug transporters. It remains unclear whether drug resistance in vitro occurs at clinically relevant doses of chemotherapy drugs and whether both the onset and magnitude of drug resistance can be temporally and causally correlated with the enhanced expression and activity of specific drug transporters. To address these issues, MCF-7 cells were selected for survival in increasing concentrations of doxorubicin (MCF-7 DOX-2 ), epirubicin (MCF-7 EPI ), paclitaxel (MCF-7 TAX-2 ), or docetaxel (MCF-7 TXT ). During selection cells were assessed for drug sensitivity, drug uptake, and the expression of various drug transporters. In all cases, resistance was only achieved when selection reached a specific threshold dose, which was well within the clinical range. A reduction in drug uptake was temporally correlated with the acquisition of drug resistance for all cell lines, but further increases in drug resistance at doses above threshold were unrelated to changes in cellular drug uptake. Elevated expression of one or more drug transporters was seen at or above the threshold dose, but the identity, number, and temporal pattern of drug transporter induction varied with the drug used as selection agent. The pan drug transporter inhibitor cyclosporin A was able to partially or completely restore drug accumulation in the drug-resistant cell lines, but had only partial to no effect on drug sensitivity. The inability of cyclosporin A to restore drug sensitivity suggests the presence of additional mechanisms of drug resistance. This study indicates that drug resistance is achieved in breast tumour cells only upon exposure to concentrations of drug at or above a specific selection dose. While changes in drug accumulation and the expression of drug transporters does occur at the threshold dose, the magnitude of

  13. Drug Facts

    Medline Plus

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

  14. Drug Facts

    Medline Plus

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

  15. 21 CFR 131.115 - Concentrated milk.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Concentrated milk. 131.115 Section 131.115 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION MILK AND CREAM Requirements for Specific Standardized Milk and Cream § 131.115...

  16. Development of an Interferometric Phased Array Trigger for Balloon-Borne Detection of the Highest Energy Cosmic Particles

    Science.gov (United States)

    Vieregg, Abigail

    Through high energy neutrino astrophysics, we explore the structure and evolution of the universe in a unique way and learn about the physics inside of astrophysical sources that drives the acceleration of the highest energy particles. Neutrinos travel virtually unimpeded through the universe, making them unique messenger particles for cosmic sources and carrying information about very distant sources that would otherwise be unavailable. The highest energy neutrinos (E>10^{18} eV), created as a by-product of the interaction of the highest energy cosmic rays with the cosmic microwave background, are an important tool for determining the origin of the highest energy cosmic rays and still await discovery. Balloon-borne and ground-based experiments are poised to discover these ultra-high energy (UHE) cosmogenic neutrinos by looking for radio emission from two different types of neutrino interactions: particle cascades induced by neutrinos in glacial ice, and extensive air showers in the atmosphere induced by the charged-particle by-product of tau neutrinos interacting in the earth. These impulsive radio detectors are also sensitive to radio emission from extensive air showers induced directly by UHE cosmic rays. Balloon-borne experiments are especially well-suited for discovering the highest energy neutrinos, and are the only way to probe the high energy cutoff of the sources themselves to reveal the astrophysics that drives the central engines inside the most energetic accelerators in the universe. Balloon platforms offer the chance to monitor extremely large volumes of ice and atmosphere, but with a higher energy threshold compared to ground-based observatories, since the neutrino interaction happens farther from the detector. This tradeoff means that the sensitivity of balloon-borne experiments, such as the Antarctic Impulsive Transient Antenna (ANITA) or the ExaVolt Antenna, is optimized for discovery of the highest energy neutrinos. We are developing an

  17. Ground-state energies and highest occupied eigenvalues of atoms in exchange-only density-functional theory

    Science.gov (United States)

    Li, Yan; Harbola, Manoj K.; Krieger, J. B.; Sahni, Viraht

    1989-11-01

    The exchange-correlation potential of the Kohn-Sham density-functional theory has recently been interpreted as the work required to move an electron against the electric field of its Fermi-Coulomb hole charge distribution. In this paper we present self-consistent results for ground-state total energies and highest occupied eigenvalues of closed subshell atoms as obtained by this formalism in the exchange-only approximation. The total energies, which are an upper bound, lie within 50 ppm of Hartree-Fock theory for atoms heavier than Be. The highest occupied eigenvalues, as a consequence of this interpretation, approximate well the experimental ionization potentials. In addition, the self-consistently calculated exchange potentials are very close to those of Talman and co-workers [J. D. Talman and W. F. Shadwick, Phys. Rev. A 14, 36 (1976); K. Aashamar, T. M. Luke, and J. D. Talman, At. Data Nucl. Data Tables 22, 443 (1978)].

  18. Substance use - prescription drugs

    Science.gov (United States)

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

  19. Herb-drug interactions.

    Science.gov (United States)

    Fugh-Berman, A

    2000-01-08

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

  20. A case-control study estimating accident risk for alcohol, medicines and illegal drugs.

    Directory of Open Access Journals (Sweden)

    Kim Paula Colette Kuypers

    Full Text Available The aim of the present study was to assess the risk of having a traffic accident after using alcohol, single drugs, or a combination, and to determine the concentrations at which this risk is significantly increased.A population-based case-control study was carried out, collecting whole blood samples of both cases and controls, in which a number of drugs were detected. The risk of having an accident when under the influence of drugs was estimated using logistic regression adjusting for gender, age and time period of accident (cases/sampling (controls. The main outcome measures were odds ratio (OR for accident risk associated with single and multiple drug use. In total, 337 cases (negative: 176; positive: 161 and 2726 controls (negative: 2425; positive: 301 were included in the study.Main findings were that 1 alcohol in general (all the concentrations together caused an elevated crash risk; 2 cannabis in general also caused an increase in accident risk; at a cut-off of 2 ng/mL THC the risk of having an accident was four times the risk associated with the lowest THC concentrations; 3 when ranking the adjusted OR from lowest to highest risk, alcohol alone or in combination with other drugs was related to a very elevated crash risk, with the highest risk for stimulants combined with sedatives.The study demonstrated a concentration-dependent crash risk for THC positive drivers. Alcohol and alcohol-drug combinations are by far the most prevalent substances in drivers and subsequently pose the largest risk in traffic, both in terms of risk and scope.

  1. Drug Facts

    Medline Plus

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

  2. Prescription Drugs

    Science.gov (United States)

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

  3. Drug Facts

    Medline Plus

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

  4. Drug Facts

    Medline Plus

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

  5. Drug Facts

    Medline Plus

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

  6. Drug Control

    Science.gov (United States)

    Leviton, Harvey S.

    1975-01-01

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

  7. Drug Facts

    Medline Plus

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

  8. Drug Facts

    Medline Plus

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

  9. Drug Facts

    Medline Plus

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

  10. Drug Facts

    Medline Plus

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

  11. Drug Facts

    Medline Plus

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

  12. Parenteral formulation of an antileishmanial drug candidate--tackling poor solubility, chemical instability, and polymorphism.

    Science.gov (United States)

    Kupetz, Eva; Preu, Lutz; Kunick, Conrad; Bunjes, Heike

    2013-11-01

    The paullon chalcone derivative KuRei300 is active against Leishmania donovani, the protozoans causing visceral leishmaniasis. The aim of this study was the development of a parenteral formulation of the virtually water insoluble compound in order to enable future studies in mice. Mixed lecithin/bile salt micelles, liposomes, supercooled smectic cholesterol myristate nanoparticles, cubic phase nanoparticles and a triglyceride emulsion were screened for their solubilizing properties. Due to the limited available amount of KuRei300 a passive loading approach with pre-formulated carriers that were incubated with drug substance deposited onto the walls of glass vials was used. The loading capacities of the nanocarriers, the influence of the solid state properties of the drug and its deposits on the loading results and chemical stability aspects of KuRei300 were investigated. Employed methods included HPLC, UV spectroscopy, (1)H NMR, XRPD, and DSC. All nanocarriers substantially improved the solubility of KuRei300; the mixed micelles exhibited the highest drug load. Related to the lipid matrix, however, the smectic nanoparticles solubilized the significantly highest amount of drug. Loading from physically altered drug deposits improved the obtainable concentration to the threefold compared with untreated drug powder. Formulations with KuRei300 must be stored excluded from light under a nitrogen atmosphere as the substance is susceptible to photoisomerization and decomposition. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Orphan drugs

    OpenAIRE

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

    2013-01-01

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

  14. Target concentration intervention: beyond Y2K.

    Science.gov (United States)

    Holford, N H

    2001-01-01

    Target concentration intervention (TCI) is proposed as an alternative conceptual strategy to therapeutic drug monitoring (TDM). It is argued that the idea of a therapeutic range has limited the interpretation of measured drug concentrations and diminished the anticipated clinical benefit to patients by use of an oversimplified pharmacodynamic model. TCI on the other hand embraces pharmacokinetic and pharmacodynamic concepts and uses the idea of a target effect and associated target concentration to make rational individual dose decisions.

  15. Drug Testing

    Science.gov (United States)

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

  16. Drug Facts

    Medline Plus

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

  17. Drug Facts

    Medline Plus

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

  18. Drug Facts

    Medline Plus

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

  19. Drug Facts

    Medline Plus

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

  20. Drug Facts

    Medline Plus

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

  1. Drug Facts

    Medline Plus

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

  2. Short communication: cheminformatics analysis to identify predictors of antiviral drug penetration into the female genital tract.

    Science.gov (United States)

    Thompson, Corbin G; Sedykh, Alexander; Nicol, Melanie R; Muratov, Eugene; Fourches, Denis; Tropsha, Alexander; Kashuba, Angela D M

    2014-11-01

    The exposure of oral antiretroviral (ARV) drugs in the female genital tract (FGT) is variable and almost unpredictable. Identifying an efficient method to find compounds with high tissue penetration would streamline the development of regimens for both HIV preexposure prophylaxis and viral reservoir targeting. Here we describe the cheminformatics investigation of diverse drugs with known FGT penetration using cluster analysis and quantitative structure-activity relationships (QSAR) modeling. A literature search over the 1950-2012 period identified 58 compounds (including 21 ARVs and representing 13 drug classes) associated with their actual concentration data for cervical or vaginal tissue, or cervicovaginal fluid. Cluster analysis revealed significant trends in the penetrative ability for certain chemotypes. QSAR models to predict genital tract concentrations normalized to blood plasma concentrations were developed with two machine learning techniques utilizing drugs' molecular descriptors and pharmacokinetic parameters as inputs. The QSAR model with the highest predictive accuracy had R(2)test=0.47. High volume of distribution, high MRP1 substrate probability, and low MRP4 substrate probability were associated with FGT concentrations ≥1.5-fold plasma concentrations. However, due to the limited FGT data available, prediction performances of all models were low. Despite this limitation, we were able to support our findings by correctly predicting the penetration class of rilpivirine and dolutegravir. With more data to enrich the models, we believe these methods could potentially enhance the current approach of clinical testing.

  3. Therapeutic drug monitoring of aminoglycosides in neonates

    NARCIS (Netherlands)

    Touw, Daniël J; Westerman, Elsbeth M; Sprij, Arwen J

    2009-01-01

    The efficacy and toxicity of aminoglycosides show a strong direct positive relationship with blood drug concentrations, therefore, therapy with aminoglycosides in adults is usually guided by therapeutic drug monitoring. Dosing regimens in adults have evolved from multiple daily dosing to

  4. Communication: The highest frequency hydrogen bond vibration and an experimental value for the dissociation energy of formic acid dimer

    DEFF Research Database (Denmark)

    Kollipost, F.; Larsen, René Wugt; Domanskaya, A.V.

    2012-01-01

    The highest frequency hydrogen bond fundamental of formic acid dimer, ν24 (Bu), is experimentally located at 264 cm−1. FTIR spectra of this in-plane bending mode of (HCOOH)2 and band centers of its symmetric D isotopologues (isotopomers) recorded in a supersonic slit jet expansion are presented...... thermodynamics treatment of the dimerization process up to room temperature. We obtain D0 = 59.5(5) kJ/mol as the best experimental estimate for the dimer dissociation energy at 0 K. Further improvements have to wait for a more consistent determination of the room temperature equilibrium constant....

  5. The Physikalisch-Technische Bundesanstalt PTB (physical-technical Federal institution) - research institute and highest technical authority

    International Nuclear Information System (INIS)

    Klages, H.

    1976-01-01

    The PTB Braunschweig and Berlin is a Federal institution for the natural sciences and engineering and the highest technical authority for measurements. It is subject to the directions of the Federal Ministry for Economic Affairs. Its main tasks are representation, maintenance and development of physical units and, in connection with this, research, examinations, and granting permissions for calibration measuring equipment, as well as examinations of building types and permissions. The types of measuring equipment are represented. Many examinations are carried out on a voluntary basis. The advisory activities and the PTB's publications are also reported on. An organizational plan informs of the structure of the PTB. (orig.) [de

  6. The Licancabur Project: Exploring the Limits of Life in the Highest Lake on Earth as an Analog to Martian Paleolakes

    Science.gov (United States)

    Cabrol, N. A.; Grin, E. A.; McKay, C. P.; Friedmann, I.; Diaz, G. Chong; Demergasso, C.; Kisse, K.; Grigorszky, I.; Friedmann, R. Ocampo; Hock, A.

    2003-01-01

    The Licancabur volcano (6017 m) hosts the highest and one of the least explored lakes in the world in its summit crater. It is located 22 deg.50 min. South / 67 deg.53 min. West at the boundary of Chile and Bolivia in the High-Andes. In a freezing environment, the lake located in volcano-tectonic environment combines low-oxygen, low atmospheric pressure due to altitude, and high-UV radiation (see table). However, its bottom water temperature remains above 0 C year-round. These conditions make Licancabur a unique analog to Martian paleolakes considered high-priority sites for the search for life on Mars.

  7. Potential need for re-definition of the highest priority recovery action in the Krsko SAG-1

    International Nuclear Information System (INIS)

    Bilic Zabric, T.; Basic, I.

    2005-01-01

    Replacement of old SG (Steam Generators) [7] and the characteristic of new ones throws the question of proper accident management strategy, which leans on philosophy that repair and recovery actions have first priority. In the current NPP Krsko SAMGs (Severe Accident Management Guidelines), water supply to the SG has priority over re-injection water into the core. NPP Krsko reconsidered the highest priority of SAG-1 (inject water to the SG), against the WOG (Westinghouse Owners Group) generic approach (inject water into the core) and potential revision of Severe Accident Phenomenology Evaluations using MAAP (Modular accident Analysis Program) 4.0.5 code. (author)

  8. Therapeutic drug monitoring of atypical antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Grundmann Milan

    2014-12-01

    Full Text Available Schizophrenia is a severe psychiatric disorder often associated with cognitive impairment and affective, mainly depressive, symptoms. Antipsychotic medication is the primary intervention for stabilization of acute psychotic episodes and prevention of recurrences and relapses in patients with schizophrenia. Typical antipsychotics, the older class of antipsychotic agents, are currently used much less frequently than newer atypical antipsychotics. Therapeutic drug monitoring (TDM of antipsychotic drugs is the specific method of clinical pharmacology, which involves measurement of drug serum concentrations followed by interpretation and good cooperation with the clinician. TDM is a powerful tool that allows tailor-made treatment for the specific needs of individual patients. It can help in monitoring adherence, dose adjustment, minimizing the risk of toxicity and in cost-effectiveness in the treatment of psychiatric disorders. The review provides complex knowledge indispensable to clinical pharmacologists, pharmacists and clinicians for interpretation of TDM results.

  9. WAr on DrugS

    African Journals Online (AJOL)

    2009-04-12

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

  10. Presentation and verification of a simple mathematical model foridentification of the areas behind noise barrierwith the highest performance

    Directory of Open Access Journals (Sweden)

    M. Monazzam

    2009-07-01

    Full Text Available Background and aims   Traffic noise barriers are the most important measure to control the environmental noise pollution. Diffraction from top edge of noise barriers is the most important path of indirect sound wave moves towards receiver.Therefore, most studies are focused on  improvement of this kind.   Methods   T-shape profile barriers are one of the most successful barrier among many different profiles. In this investigation the theory of destructive effect of diffracted waves from real edge of barrier and the wave diffracted from image of the barrier with phase difference of radians is used. Firstly a simple mathematical representation of the zones behind rigid and absorbent T- shape barriers with the highest insertion loss using the destructive effect of indirect path via barrier  image is introduced and then two different profile reflective and absorption barrier is used for  verification of the introduced model   Results   The results are then compared with the results of a verified two dimensional boundary element method at 1/3 octave band frequencies and in a wide field behind those barriers. Avery good agreement between the results has been achieved. In this method effective height is used for any different profile barriers.   Conclusion   The introduced model is very simple, flexible and fast and could be used for choosing the best location of profile rigid and absorptive barriers to achieve the highest  performance.  

  11. The Idea of a Highest Divine Principle — Founding Reason and Spirituality. A Necessary Concept of a Comparative Philosophy?

    Directory of Open Access Journals (Sweden)

    Claudia Bickmann

    2012-10-01

    Full Text Available By reference to the Platonic, Aristotelian, and Neo-Platonic philosophical traditions (and then to German Idealism, including Husserl and Heidegger, I will indicate the way in which the concept of reason—on the one side—depends on the horizon of spirituality (by searching for the ultimate ground within us and the striving for the highest good; and inversely—how far the idea of the divine or our spiritual self may be deepened, understood and transmitted by reference to reason and rationality. But whereas philosophical analysis aims at the universal dimensions of spirituality or the divine (as in Plato's idea of the 'highest good', the Aristotelian 'Absolute substance', the 'Oneness of the One' (Plotinus and the Neo-Platonists or the Hegelian 'Absolute spirit',—Comparative Theology may preserve the dimension of spirituality or divinity in its individuality and specifity. Comparative Theology mediates between the universality of the philosophical discourse and the uniqueness of our individual experience (symbolized by a sacred person—such as Jesus, Brahman, Buddha or Mohammed by reflecting and analyzing our religious experiences and practices. Religion may lose its specificity by comparative conceptual analysis within the field of philosophy, but Comparative Theology may enhance the vital dimensions of the very same spiritual experience by placing them in a comparative perspective.

  12. Increased Risk of Drug-Induced Hyponatremia during High Temperatures

    Directory of Open Access Journals (Sweden)

    Anna K Jönsson

    2017-07-01

    Full Text Available Purpose: To investigate the relationship between outdoor temperature in Sweden and the reporting of drug-induced hyponatremia to the Medical Products Agency (MPA. Methods: All individual adverse drug reactions (ADR reported to MPA from 1 January 2010 to 31 October 2013 of suspected drug-induced hyponatremia and random controls were identified. Reports where the ADR had been assessed as having at least a possible relation to the suspected drug were included. Information on administered drugs, onset date, causality assessment, sodium levels, and the geographical origin of the reports was extracted. A case-crossover design was used to ascertain the association between heat exposure and drug-induced hyponatremia at the individual level, while linear regression was used to study its relationship to sodium concentration in blood. Temperature exposure data were obtained from the nearest observation station to the reported cases. Results: During the study period, 280 reports of hyponatremia were identified. More cases of drug-induced hyponatremia were reported in the warmer season, with a peak in June, while other ADRs showed an opposite annual pattern. The distributed lag non-linear model indicated an increasing odds ratio (OR with increasing temperature in the warm season with a highest odds ratio, with delays of 1–5 days after heat exposure. A cumulative OR for a lag time of 1 to 3 days was estimated at 2.21 at an average daily temperature of 20 °C. The change in sodium per 1 °C increase in temperature was estimated to be −0.37 mmol/L (95% CI: −0.02, −0.72. Conclusions: Warm weather appears to increase the risk of drug-induced hyponatremia

  13. Impaired psychomotor function and plasma methadone and levo-alpha-acetylmethadol (LAAM) concentrations in opioid-substitution patients.

    Science.gov (United States)

    Newcombe, David A L; Somogyi, Andrew A; Bochner, Felix; White, Jason M

    2017-06-01

    Tolerance to the psychomotor impairing effects of opioid drugs is expected to develop with repeated dosing, but may be incomplete. The relationship between plasma opioid concentration and psychomotor function in opioid-dependent patients was examined to determine whether impairment was more likely at the time of highest plasma drug concentration. Sixteen patients participating in a cross-over trial comparing methadone and LAAM completed a tracking task (OSPAT) 11 times over the dosing-interval for methadone (24-hrs) and LAAM (48-hrs). Venous blood was collected for the quantification of plasma (R)-(-)-methadone, LAAM, and nor-LAAM concentrations. The Digit Symbol Substitution Test (DSST) and Trail-Making Test were administered at the time of peak plasma concentration. Ten healthy controls (HCs) also participated. OSPAT scores (obtained for 15 patients) fluctuated significantly across the dosing-interval for both drugs and were lower in patients than HCs at the times of peak concentrations of (R)-(-)-methadone (1 hr: (mean difference; 95% CI) (2.13; 0.18-4.08); 2 hrs: (2.38; 0.48-4.28) postdosing) and LAAM (2 hrs: (1.81; 0.09-3.53), and 4 hrs (1.90: 0.9-3.71) postdosing). Within-participant analysis of the peak-change from baseline for OSPAT scores found that 10 of the 15 patients could be categorized as impaired on methadone and 9 on LAAM. No HCs were impaired. Patients performed worse on the DSST and Trails-A than HCs, but not on Trails-B. Results suggest that some patients receiving opioids long term may exhibit impairment at the time of highest plasma drug concentration. These patients should be made aware that their ability to undertake complex tasks may be affected. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  14. A new self-emulsifying formulation of mefenamic acid with enhanced drug dissolution

    Directory of Open Access Journals (Sweden)

    Pornsak Sriamornsak

    2015-04-01

    Full Text Available To enhance the dissolution of poorly soluble mefenamic acid, self-emulsifying formulation (SEF, composing of oil, surfactant and co-surfactant, was formulated. Among the oils and surfactants studied, Imwitor® 742, Tween® 60, Cremophore® EL and Transcutol® HP were selected as they showed maximal solubility to mefenamic acid. The ternary phase diagram was constructed to find optimal concentration that provided the highest drug loading. The droplet size after dispersion and drug dissolution of selected formulations were investigated. The results showed that the formulation containing Imwitor® 742, Tween® 60 and Transcutol® HP (10:30:60 can encapsulate high amount of mefenamic acid. The dissolution study demonstrated that, in the medium containing surfactant, nearly 100% of mefenamic acid were dissolved from SEF within 5 min while 80% of drugs were dissolved from the commercial product in 45 min. In phosphate buffer (without surfactant, 80% of drug were dissolved from the developed SEF within 5 min while only about 13% of drug were dissolved in 45 min, from the commercial product. The results suggested that the SEF can enhance the dissolution of poorly soluble drug and has a potential to enhance drug absorption and improve bioavailability of drug.

  15. Prevalence of alcohol and drugs among car and van drivers killed in road accidents in Norway: an overview from 2001 to 2010.

    Science.gov (United States)

    Christophersen, Asbjørg S; Gjerde, Hallvard

    2014-01-01

    To examine the prevalence of alcohol and drugs in blood samples collected from car and van drivers killed in traffic accidents in Norway during the time period from 2001 to 2010. Blood samples (n = 676, 63% of all killed drivers) were analyzed for alcohol, psychoactive medications, and illicit drugs. The cutoff limits for positive results were set according to the new legislative limits under the Norwegian Road Traffic Act. The results were assessed in relation to sex and age, time of day and day of week, and single- versus multiple-vehicle and all investigated vehicle accidents. Alcohol or one or more drugs was detected in samples from 40.2 percent of all investigated drivers, with 28.7 percent showing blood concentrations of at least 5 times the legislative limits. For the investigated female drivers, the total prevalence was 24.0 percent. Among the single-vehicle accidents, alcohol or drugs was found in 63.8 percent of the cases, with 49.1 percent showing blood concentrations of at least 5 times the legislative limits. Alcohol was detected in 25.3 and 49.1 percent of samples from all investigated drivers and among drivers killed in single-vehicle accidents, respectively. Psychoactive medications were found in 14.4 and 17.7 percent and illicit drugs in 14.1 and 19.2 percent, respectively. The most commonly detected group of medications was benzodiazepines, and amphetamines and tetrahydrocannabinol were the most commonly detected illicit drugs. The prevalence of alcohol alone was highest among drivers under the age of 25, and the combination of alcohol with other drugs was highest among drivers under the age of 35. Drivers between the ages of 25 and 54 showed the highest prevalence of medications and/or illicit drugs without the presence of alcohol. The highest prevalence of alcohol or drugs was found among drivers killed in single-vehicle accidents on weeknights (83.8%) and on weekend nights (89.3%). The findings confirm that a large number of fatally injured

  16. Who jumps the highest? Anthropometric and physiological correlations of vertical jump in youth elite female volleyball players.

    Science.gov (United States)

    Nikolaidis, Pantelis T; Gkoudas, Konstantinos; Afonso, José; Clemente-Suarez, Vicente J; Knechtle, Beat; Kasabalis, Stavros; Kasabalis, Athanasios; Douda, Helen; Tokmakidis, Savvas; Torres-Luque, Gema

    2017-06-01

    The aim of the present study was to examine the relationship of vertical jump (Abalakov jump [AJ]) with anthropometric and physiological parameters in youth elite female volleyball players. Seventy-two selected volleyball players from the region of Athens (age 13.3±0.7 years, body mass 62.0±7.2 kg, height 171.5±5.7 cm, body fat 21.2±4.5%), classified into quartiles according to AJ performance (group A, 21.4-26.5 cm; group B, 26.8-29.9 cm; group C, 30.5-33.7 cm; group D, 33.8-45.9 cm), performed a series of physical fitness tests. AJ was correlated with anthropometric (age at peak height velocity [APHV]: r=0.38, Pvolleyball players that jumped the highest were those who matured later than others.

  17. Repeated Radionuclide therapy in metastatic paraganglioma leading to the highest reported cumulative activity of 131I-MIBG

    International Nuclear Information System (INIS)

    Ezziddin, Samer; Sabet, Amir; Ko, Yon-Dschun; Xun, Sunny; Matthies, Alexander; Biersack, Hans-Jürgen

    2012-01-01

    131 I-MIBG therapy for neuroendocrine tumours may be dose limited. The common range of applied cumulative activities is 10-40 GBq. We report the uneventful cumulative administration of 111 GBq (= 3 Ci) 131 I-MIBG in a patient with metastatic paraganglioma. Ten courses of 131 I-MIBG therapy were given within six years, accomplishing symptomatic, hormonal and tumour responses with no serious adverse effects. Chemotherapy with cisplatin/vinblastine/dacarbazine was the final treatment modality with temporary control of disease, but eventually the patient died of progression. The observed cumulative activity of 131 I-MIBG represents the highest value reported to our knowledge, and even though 12.6 GBq of 90 Y-DOTATOC were added intermediately, no associated relevant bone marrow, hepatic or other toxicity were observed. In an individual attempt to palliate metastatic disease high cumulative activity alone should not preclude the patient from repeat treatment

  18. Impact of thermal frequency drift on highest precision force microscopy using quartz-based force sensors at low temperatures

    Directory of Open Access Journals (Sweden)

    Florian Pielmeier

    2014-04-01

    Full Text Available In frequency modulation atomic force microscopy (FM-AFM the stability of the eigenfrequency of the force sensor is of key importance for highest precision force measurements. Here, we study the influence of temperature changes on the resonance frequency of force sensors made of quartz, in a temperature range from 4.8–48 K. The sensors are based on the qPlus and length extensional principle. The frequency variation with temperature T for all sensors is negative up to 30 K and on the order of 1 ppm/K, up to 13 K, where a distinct kink appears, it is linear. Furthermore, we characterize a new type of miniaturized qPlus sensor and confirm the theoretically predicted reduction in detector noise.

  19. Analysis of the highest transverse energy events seen in the UAl detector at the Spp-barS collider

    International Nuclear Information System (INIS)

    1987-06-01

    The first full solid angle analysis is presented of large transverse energy events in pp-bar collisions at the CERN collider. Events with transverse energies in excess of 200 GeV at √s = 630 GeV are studied for any non-standard physics and quantitatively compared with expectations from perturbative QCD Monte Carlo models. A corrected differential cross section is presented. A detailed examination is made of jet profiles, event jet multiplicities and the fraction of the transverse energy carried by the two jets with the highest transverse jet energies. There is good agreement with standard theory for events with transverse energies up to the largest observed values (approx. √s/2) and the analysis shows no evidence for any non-QCD mechanism to account for the event characteristics. (author)

  20. A common founder mutation in FANCA underlies the world's highest prevalence of Fanconi anemia in Gypsy families from Spain.

    Science.gov (United States)

    Callén, Elsa; Casado, José A; Tischkowitz, Marc D; Bueren, Juan A; Creus, Amadeu; Marcos, Ricard; Dasí, Angeles; Estella, Jesús M; Muñoz, Arturo; Ortega, Juan J; de Winter, Johan; Joenje, Hans; Schindler, Detlev; Hanenberg, Helmut; Hodgson, Shirley V; Mathew, Christopher G; Surrallés, Jordi

    2005-03-01

    Fanconi anemia (FA) is a genetic disease characterized by bone marrow failure and cancer predisposition. Here we have identified Spanish Gypsies as the ethnic group with the world's highest prevalence of FA (carrier frequency of 1/64-1/70). DNA sequencing of the FANCA gene in 8 unrelated Spanish Gypsy FA families after retroviral subtyping revealed a homozygous FANCA mutation (295C>T) leading to FANCA truncation and FA pathway disruption. This mutation appeared specific for Spanish Gypsies as it is not found in other Gypsy patients with FA from Hungary, Germany, Slovakia, and Ireland. Haplotype analysis showed that Spanish Gypsy patients all share the same haplotype. Our data thus suggest that the high incidence of FA among Spanish Gypsies is due to an ancestral founder mutation in FANCA that originated in Spain less than 600 years ago. The high carrier frequency makes the Spanish Gypsies a population model to study FA heterozygote mutations in cancer.

  1. Analysis of the highest transverse energy events seen in the UA1 detector at the Spanti pS collider

    International Nuclear Information System (INIS)

    Albajar, C.; Bezaguet, A.; Cennini, P.

    1987-01-01

    This is the first full solid angle analysis of large transverse energy events in panti p collisions at the CERN collider. Events with transverse energies in excess of 200 GeV at √s=630 GeV are studied for any non-standard physics and quantitatively compared with expectations from perturbative QCD Monte Carlo models. A corrected differential cross section is presented. A detailed examination is made of jet profiles, event jet multiplicities and the fraction of the transverse energy carried by the two jets with the highest transverse jet energies. There is good agreement with standard theory for events with transverse energies up to the largest observed values (≅ √s/2) and the analysis shows no evidence for any non-QCD mechanism to account for the event characteristics. (orig.)

  2. The Mass Elevation Effect of the Central Andes and Its Implications for the Southern Hemisphere's Highest Treeline

    Directory of Open Access Journals (Sweden)

    Wenhui He

    2016-05-01

    Full Text Available One of the highest treelines in the world is at 4810 m above sea level on the Sajama Volcano in the central Andes. The climatological cause of that exceptionally high treeline position is still unclear. Although it has been suggested that the mass elevation effect (MEE explains the upward shift of treelines in the Altiplano region, the magnitude of MEE has not yet been quantified for that region. This paper defines MEE as the air temperature difference in summer at the same elevation between the inner mountains/plateaus (Altiplano and the free atmosphere above the adjacent lowlands of the Andean Cordillera. The Altiplano air temperature was obtained from the Global Historical Climatology Network-Monthly temperature database, and the air temperature above the adjacent lowlands was interpolated based on the National Center for Environmental Prediction/National Center for Atmospheric Research Reanalysis 1 data set. We analyzed the mean air temperature differences for January, July, and the warm months from October to April. The air temperature was mostly higher on the Altiplano than over the neighboring lowlands at the same altitude. The air temperature difference increased from the outer Andean east-facing slope to the interior of the Altiplano in summer, and it increased from high latitudes to low latitudes in winter. The mean air temperature in the Altiplano in summer is approximately 5 K higher than it is above the adjacent lowlands at the same mean elevation, averaging about 3700 m above sea level. This upward shift of isotherms in the inner part of the Cordillera enables the treeline to climb to 4810 m, with shrub-size trees reaching even higher. Therefore, the MEE explains the occurrence of one of the world’s highest treelines in the central Andes.

  3. Contact with HIV prevention services highest in gay and bisexual men at greatest risk: cross-sectional survey in Scotland

    Directory of Open Access Journals (Sweden)

    Hart Graham J

    2010-12-01

    Full Text Available Abstract Background Men who have sex with men (MSM remain the group most at risk of acquiring HIV in the UK and new HIV prevention strategies are needed. In this paper, we examine what contact MSM currently have with HIV prevention activities and assess the extent to which these could be utilised further. Methods Anonymous, self-complete questionnaires and Orasure™ oral fluid collection kits were distributed to men visiting the commercial gay scenes in Glasgow and Edinburgh in April/May 2008. 1508 men completed questionnaires (70.5% response rate and 1277 provided oral fluid samples (59.7% response rate; 1318 men were eligible for inclusion in the analyses. Results 82.5% reported some contact with HIV prevention activities in the past 12 months, 73.1% obtained free condoms from a gay venue or the Internet, 51.1% reported accessing sexual health information (from either leaflets in gay venues or via the Internet, 13.5% reported talking to an outreach worker and 8.0% reported participating in counselling on sexual health or HIV prevention. Contact with HIV prevention activities was associated with frequency of gay scene use and either HIV or other STI testing in the past 12 months, but not with sexual risk behaviours. Utilising counselling was also more likely among men who reported having had an STI in the past 12 months and HIV-positive men. Conclusions Men at highest risk, and those likely to be in contact with sexual health services, are those who report most contact with a range of current HIV prevention activities. Offering combination prevention, including outreach by peer health workers, increased uptake of sexual health services delivering behavioural and biomedical interventions, and supported by social marketing to ensure continued community engagement and support, could be the way forward. Focused investment in the needs of those at highest risk, including those diagnosed HIV-positive, may generate a prevention dividend in the long

  4. COPD - control drugs

    Science.gov (United States)

    Chronic obstructive pulmonary disease - control drugs; Bronchodilators - COPD - control drugs; Beta agonist inhaler - COPD - control drugs; Anticholinergic inhaler - COPD - control drugs; Long-acting inhaler - COPD - control drugs; ...

  5. [Orphan drugs].

    Science.gov (United States)

    Golocorbin Kon, Svetlana; Vojinović, Aleksandra; Lalić-Popović, Mladena; Pavlović, Nebojsa; Mikov, Momir

    2013-01-01

    Drugs used for treatment of rare diseases are known worldwide under the term of orphan drugs because pharmaceutical companies have not been interested in "adopting" them, that is in investing in research, developing and producing these drugs. This kind of policy has been justified by the fact that these drugs are targeted for small markets, that only a small number of patients is available for clinical trials, and that large investments are required for the development of drugs meant to treat diseases whose pathogenesis has not yet been clarified in majority of cases. The aim of this paper is to present previous and present status of orphan drugs in Serbia and other countries. THE BEGINNING OF ORPHAN DRUGS DEVELOPMENT: This problem was first recognized by Congress of the United States of America in January 1983, and when the "Orphan Drug Act" was passed, it was a turning point in the development of orphan drugs. This law provides pharmaceutical companies with a series of reliefs, both financial ones that allow them to regain funds invested into the research and development and regulatory ones. Seven years of marketing exclusivity, as a type of patent monopoly, is the most important relief that enables companies to make large profits. There are no sufficient funds and institutions to give financial support to the patients. It is therefore necessary to make health professionals much more aware of rare diseases in order to avoid time loss in making the right diagnosis and thus to gain more time to treat rare diseases. The importance of discovery, development and production of orphan drugs lies in the number of patients whose life quality can be improved significantly by administration of these drugs as well as in the number of potential survivals resulting from the treatment with these drugs.

  6. AIDSinfo Drug Database

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content Drugs Home Drugs Find information on FDA-approved HIV/ ... infection drugs and investigational HIV/AIDS drugs. Search Drugs Search drug Search Icon What's this? Close Popup ...

  7. Influence of molar mass, dispersity, and type and location of hydrophobic side chain moieties on the critical micellar concentration and stability of amphiphilic HPMA-based polymer drug carriers

    Czech Academy of Sciences Publication Activity Database

    Filippov, Sergey K.; Vishnevetskaya, N. S.; Niebuur, B.-J.; Koziolová, Eva; Lomkova, Ekaterina A.; Chytil, Petr; Etrych, Tomáš; Papadakis, C. M.

    2017-01-01

    Roč. 295, č. 8 (2017), s. 1313-1325 ISSN 0303-402X R&D Projects: GA MZd(CZ) NV16-28600A; GA ČR(CZ) GC15-10527J Institutional support: RVO:61389013 Keywords : drug delivery * HPMA copolymers * fluorescence correlation spectroscopy Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 1.723, year: 2016

  8. Prevalence and sunlight photolysis of controlled and chemotherapeutic drugs in aqueous environments

    International Nuclear Information System (INIS)

    Lin, Angela Yu-Chen; Lin, Yen-Ching; Lee, Wan-Ning

    2014-01-01

    This study addresses the occurrences and natural fates of chemotherapeutics and controlled drugs when found together in hospital effluents and surface waters. The results revealed the presence of 11 out of 16 drugs in hospital effluents, and the maximum detected concentrations were at the μg L −1 level in the hospital effluents and the ng L −1 level in surface waters. The highest concentrations corresponded to meperidine, morphine, 5-fluorouracil and cyclophosphamide. The sunlight photolysis of the target compounds was investigated, and the results indicated that morphine and codeine can be significantly attenuated, with half-lives of 0.27 and 2.5 h, respectively, in natural waters. Photolysis can lower the detected environmental concentrations, also lowering the estimated environmental risks of the target drugs to human health. Nevertheless, 5-fluorouracil and codeine were found to have a high risk quotient (RQ), demonstrating the high risks of directly releasing hospital wastewater into the environment. - Highlights: • High occurrence of chemotherapeutics and controlled substances in aqueous systems. • Photolysis lowers the detected concentrations of morphine and codeine. • 5-fluorouracil and codeine in hospital effluents have high risk quotients. - Chemotherapeutics and controlled drugs occur at significant levels in hospital effluents and surface waters. Natural sunlight photolysis reduces their environmental occurrence

  9. Occurrence of illicit drugs and selected pharmaceuticals in Slovak municipal wastewater.

    Science.gov (United States)

    Bodík, Igor; Mackuľak, Tomáš; Fáberová, Milota; Ivanová, Lucia

    2016-10-01

    We analyzed illicit drugs and their metabolites and pharmaceuticals in wastewater from 15 selected wastewater treatment plants (WWTPs) in Slovakia. Our results indicate that methamphetamine is one of the most commonly used illegal drugs in all the regions of Slovakia monitored in this study. Compared with the international results, the Slovak cities of Dunajská Streda (479 mg/day/1000inh) and Trnava (354 mg/day/1000inh) are among the cities with the largest numbers of methamphetamine users in Europe. These results indicate an increase in the incidence of drugs in big cities and in the satellite cities (Trnava and Dunajská Streda) near Bratislava. These results also confirm the police statistics about production and use of illicit drugs in Slovakia. The highest specific loads of cocaine were found in Bratislava (112 mg/day/1000inh), followed by Petržalka (74 mg/day/1000inh). Compared with other European cities, Bratislava and the other Slovak cities in this study have a relatively low number of COC consumers. The ecstasy load in wastewater from larger cities also significantly increased over the weekend and during music festivals. The highest 2-year mean concentrations of THC-COOH, a cannabis biomarker, were observed in the sewage from BA-Petržalka and BA-Central (191 and 171 ng/L, respectively). A first complex monitoring of pharmaceuticals in all therapeutic groups was also realized in selected Slovak WWTPs. Occurrence of wide spectrum of pharmaceuticals with very high concentrations as well as consumptions were observed mainly in small Slovak cities. Considering all 120 monitored pharmaceuticals, Valsartan had the highest concentrations: 6000 ng/L, on average.

  10. Blood lead concentration and related factors in Korea from the 2008 National Survey for Environmental Pollutants in the Human Body.

    Science.gov (United States)

    Jeong, Seong Wook; Lee, Chae Kwan; Suh, Chun Hui; Kim, Kun Hyung; Son, Byung Chul; Kim, Jeong Ho; Lee, Jong Tae; Lee, Soo Woong; Park, Yeong Beom; Lee, Jong Wha; Yu, Seung-Do; Moon, Chan Seok; Kim, Dae Hwan; Lee, Sang Yoon

    2014-11-01

    This study evaluated blood lead concentrations in the Korean general population and the correlation between various exposure sources using data from the 2008 Korea National Survey for Environmental Pollutants in the Human Body (National Institute of Environmental Research, Korea). The general and occupational characteristics were gathered from 5136 participants who were 20 years of age and older using a structured questionnaire. Blood lead concentrations were analyzed using an atomic absorption spectrophotometer. Statistical analysis was performed using multiple linear regressions of the log lead concentrations to the independent variables such as age, gender, smoke, herbal medication and drug consumption, drinking water, and living area. Geometric mean (GM) blood lead concentrations in Korean adults were 19.7 μg/l. The blood lead concentrations increased with age; the highest concentrations were found in the 50-69-year age group (pdrug consumption were higher than those who did not (plead concentration (plead concentration (plead concentration, but not significantly. For drinking water, the underground water (spring or well water) drinking group had higher concentrations than other types of water drinking groups, but not significantly (p=0.063). The blood lead concentrations by occupation were significant (plead concentrations tended to decrease with increasing delivery times, but not significantly. The blood lead concentration (GM) of the general adult population in Korea has decreased over time from 45.8 μg/l (1999) to 19.7 μg/l (2008). Although it is still higher than in other countries such as the United States and Canada, it is rapidly decreasing. Gender, age, smoking and alcohol drinking status, herbal medication and drug consumption, education level, living area and occupation were significantly related to the blood lead concentrations in Korea. Copyright © 2014. Published by Elsevier GmbH.

  11. Drug affordability-potential tool for comparing illicit drug markets.

    Science.gov (United States)

    Groshkova, Teodora; Cunningham, Andrew; Royuela, Luis; Singleton, Nicola; Saggers, Tony; Sedefov, Roumen

    2018-06-01

    The importance of illicit drug price data and making appropriate adjustments for purity has been repeatedly highlighted for understanding illicit drug markets. The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) has been collecting retail price data for a number of drug types alongside drug-specific purity information for over 15 years. While these data are useful for a number of monitoring and analytical purposes, they are not without their limitations and there are circumstances where additional adjustment needs to be considered. This paper reviews some conceptual issues and measurement challenges relevant to the interpretation of price data. It also highlights the issues with between-country comparisons of drug prices and introduces the concept of affordability of drugs, going beyond purity-adjustment to account for varying national economies. Based on a 2015 European data set of price and purity data across the heroin and cocaine retail markets, the paper demonstrates a new model for drug market comparative analysis; calculation of drug affordability is achieved by applying to purity-adjusted prices 2015 Price Level Indices (PLI, Eurostat). Available data allowed retail heroin and cocaine market comparison for 27 European countries. The lowest and highest unadjusted prices per gram were observed for heroin: in Estonia, Belgium, Greece and Bulgaria (lowest) and Finland, Ireland, Sweden and Latvia (highest); for cocaine: the Netherlands, Belgium and the United Kingdom (lowest) and Turkey, Finland, Estonia and Romania (highest). The affordability per gram of heroin and cocaine when taking into account adjustment for both purity and economy demonstrates different patterns. It is argued that purity-adjusted price alone provides an incomplete comparison of retail price across countries. The proposed new method takes account of the differing economic conditions within European countries, thus providing a more sophisticated tool for cross

  12. Drug Facts

    Medline Plus

    Full Text Available ... Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of Abuse What ... Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800- ...

  13. Drug Facts

    Medline Plus

    Full Text Available ... Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? ... Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800-662- ...

  14. Antineoplastic Drugs

    Science.gov (United States)

    Sadée, Wolfgang; El Sayed, Yousry Mahmoud

    The limited scope of therapeutic drug-level monitoring in cancer chemotherapy results from the often complex biochemical mechanisms that contribute to antineoplastic activity and obscure the relationships among drug serum levels and therapeutic benefits. Moreover, new agents for cancer chemotherapy are being introduced at a more rapid rate than for the treatment of other diseases, although the successful application of therapeutic drug-level monitoring may require several years of intensive study of the significance of serum drug levels. However, drug level monitoring can be of considerable value during phase I clinical trials of new antineoplastic agents in order to assess drug metabolism, bioavailability, and intersubject variability; these are important parameters in the interpretation of clinical studies, but have no immediate benefit to the patient. High performance liquid chromatography (HPLC) probably represents the most versatile and easily adaptable analytical technique for drug metabolite screening (1). HPLC may therefore now be the method of choice during phase I clinical trials of antineoplastic drugs. For example, within a single week we developed an HPLC assay—using a C18 reverse-phase column, UV detection, and direct serum injection after protein precipitation—for the new radiosensitizer, misonidazole (2).

  15. Drugged Driving

    Science.gov (United States)

    ... Survey Results Synthetic Cannabinoids (K2/Spice) Unpredictable Danger Drug and Alcohol Use in College-Age Adults in 2016 Monitoring the Future 2016 Survey Results Drug and Alcohol Use in College-Age Adults in 2015 View All NIDA Home ...

  16. ACHIEVEMENT OF THE HIGHEST LEVEL OF SAFETY AND HEALTH AT WORK AND THE SATISFACTION OF EMPLOYEES IN THE TEXTILE INDUSTRY

    Directory of Open Access Journals (Sweden)

    Snezana Urosevic

    2016-12-01

    Full Text Available Safety and health at work involves the exercise of such working conditions that take certain measures and activities in order to protect the life and health of employees. The interest of society, of all stakeholders and every individual is to achieve the highest level of safety and health at work, to unwanted consequences such as injuries, occupational diseases and diseases related to work are reduced to a minimum, and to create the conditions work in which employees have a sense of satisfaction in the performance of their professional duties. Textile industry is a sector with higher risk, because the plants of textile industry prevailing unfavorable microclimate conditions: high air temperature and high humidity, and often insufficient illumination of rooms and increased noise. The whole line of production in the textile industry, there is a risk of injury, the most common with mechanical force, or gaining burns from heat or chemicals. All of these factors are present in the process of production and processing of textiles and the same may affect the incidence of occupational diseases of workers, absenteeism, reduction of their working capacity and productivity. With the progress of the textile industry production increases in the number of hazardous and harmful substances that may pose a potential danger to the employee in this branch of the economy as well as the harmful impact on the environment. Therefore, it is important to give special attention to these problems.

  17. Density functional theory, comparative vibrational spectroscopic studies, highest occupied molecular orbital and lowest unoccupied molecular orbital analysis of Linezolid

    Science.gov (United States)

    Rajalakshmi, K.; Gunasekaran, S.; Kumaresan, S.

    2015-06-01

    The Fourier transform infrared spectra and Fourier transform Raman spectra of Linezolid have been recorded in the regions 4,000-400 and 4,000-100 cm-1, respectively. Utilizing the observed Fourier transform infrared spectra and Fourier transform Raman spectra data, a complete vibrational assignment and analysis of the fundamental modes of the compound have been carried out. The optimum molecular geometry, harmonic vibrational frequencies, infrared intensities and Raman scattering activities, have been calculated by density functional theory with 6-31G(d,p), 6-311G(d,p) and M06-2X/6-31G(d,p) levels. The difference between the observed and scaled wavenumber values of most of the fundamentals is very small. A detailed interpretation of the infrared and Raman spectra of Linezolid is reported. Mulliken's net charges have also been calculated. Ultraviolet-visible spectrum of the title molecule has also been calculated using time-dependent density functional method. Besides, molecular electrostatic potential, highest occupied molecular orbital and lowest unoccupied molecular orbital analysis and several thermodynamic properties have been performed by the density functional theoretical method.

  18. New hybrid magnet system for structure research at highest magnetic fields and temperatures in the millikelvin region

    International Nuclear Information System (INIS)

    Smeibidl, Peter; Ehmler, Hartmut; Tennant, Alan; Bird, Mark

    2012-01-01

    The Helmholtz Centre Berlin (HZB) is a user facility for the study of structure and dynamics with neutrons and synchrotron radiation with special emphasis on experiments under extreme conditions. Neutron scattering is uniquely suited to study magnetic properties on a microscopic length scale, because neutrons have comparable wavelengths and, due to their magnetic moment, they interact with the atomic magnetic moments. At HZB a dedicated instrument for neutron scattering at extreme magnetic fields and low temperatures is under construction, the Extreme Environment Diffractometer ExED. It is projected according to the time-of-flight principle for elastic and inelastic neutron scattering and for the special geometric constraints of analysing samples in a high field magnet. The new hybrid magnet will not only allow for novel experiments, it will be at the forefront of development in magnet technology itself. With a set of superconducting and resistive coils a maximum field above 30 T will be possible. To compromise between the needs of the magnet design for highest fields and the concept of the neutron instrument, the magnetic field will be generated by means of a coned, resistive inner solenoid and a superconducting outer solenoid with horizontal field orientation. To allow for experiments down to Millikelvin Temperatures the installation of a 3 He or a dilution cryostat with a closed cycle precooling stage is foreseen.

  19. Pleistocene climatic oscillations rather than recent human disturbance influence genetic diversity in one of the world's highest treeline species.

    Science.gov (United States)

    Peng, Yanling; Lachmuth, Susanne; Gallegos, Silvia C; Kessler, Michael; Ramsay, Paul M; Renison, Daniel; Suarez, Ricardo; Hensen, Isabell

    2015-10-01

    Biological responses to climatic change usually leave imprints on the genetic diversity and structure of plants. Information on the current genetic diversity and structure of dominant tree species has facilitated our general understanding of phylogeographical patterns. Using amplified fragment length polymorphism (AFLPs), we compared genetic diversity and structure of 384 adults of P. tarapacana with those of 384 seedlings across 32 forest sites spanning a latitudinal gradient of 600 km occurring between 4100 m and 5000 m a.s.l. in Polylepis tarapacana (Rosaceae), one of the world's highest treeline species endemic to the central Andes. Moderate to high levels of genetic diversity and low genetic differentiation were detected in both adults and seedlings, with levels of genetic diversity and differentiation being almost identical. Four slightly genetically divergent clusters were identified that accorded to differing geographical regions. Genetic diversity decreased from south to north and with increasing precipitation for adults and seedlings, but there was no relationship to elevation. Our study shows that, unlike the case for other Andean treeline species, recent human activities have not affected the genetic structure of P. tarapacana, possibly because its inhospitable habitat is unsuitable for agriculture. The current genetic pattern of P. tarapacana points to a historically more widespread distribution at lower altitudes, which allowed considerable gene flow possibly during the glacial periods of the Pleistocene epoch, and also suggests that the northern Argentinean Andes may have served as a refugium for historical populations. © 2015 Botanical Society of America.

  20. A Systematic Study to Optimize SiPM Photo-Detectors for Highest Time Resolution in PET

    CERN Document Server

    Gundacker, S.; Frisch, B.; Hillemanns, H.; Jarron, P.; Meyer, T.; Pauwels, K.; Lecoq, P.

    2012-01-01

    We report on a systematic study of time resolution made with three different commercial silicon photomultipliers (SiPMs) (Hamamatsu MPPC S10931-025P, S10931-050P, and S10931-100P) and two LSO scintillating crystals. This study aimed to determine the optimum detector conditions for highest time resolution in a prospective time-of-flight positron emission tomography (TOF-PET) system. Measurements were based on the time over threshold method in a coincidence setup using the ultrafast amplifier-discriminator NINO and a fast oscilloscope. Our tests with the three SiPMs of the same area but of different SPAD sizes and fill factors led to best results with the Hamamatsu type of 50×50×μm2 single-pixel size. For this type of SiPM and under realistic geometrical PET scanner conditions, i.e., with 2×2×10×mm3 LSO crystals, a coincidence time resolution of 220 ±4 ps FWHM could be achieved. The results are interpreted in terms of SiPM photon detection efficiency (PDE), dark noise, and photon yield.

  1. Site characterization of the highest-priority geologic formations for CO2 storage in Wyoming

    Energy Technology Data Exchange (ETDEWEB)

    Surdam, Ronald C. [Univ. of Wyoming, Laramie, WY (United States); Bentley, Ramsey [Univ. of Wyoming, Laramie, WY (United States); Campbell-Stone, Erin [Univ. of Wyoming, Laramie, WY (United States); Dahl, Shanna [Univ. of Wyoming, Laramie, WY (United States); Deiss, Allory [Univ. of Wyoming, Laramie, WY (United States); Ganshin, Yuri [Univ. of Wyoming, Laramie, WY (United States); Jiao, Zunsheng [Univ. of Wyoming, Laramie, WY (United States); Kaszuba, John [Univ. of Wyoming, Laramie, WY (United States); Mallick, Subhashis [Univ. of Wyoming, Laramie, WY (United States); McLaughlin, Fred [Univ. of Wyoming, Laramie, WY (United States); Myers, James [Univ. of Wyoming, Laramie, WY (United States); Quillinan, Scott [Univ. of Wyoming, Laramie, WY (United States)

    2013-12-07

    This study, funded by U.S. Department of Energy National Energy Technology Laboratory award DE-FE0002142 along with the state of Wyoming, uses outcrop and core observations, a diverse electric log suite, a VSP survey, in-bore testing (DST, injection tests, and fluid sampling), a variety of rock/fluid analyses, and a wide range of seismic attributes derived from a 3-D seismic survey to thoroughly characterize the highest-potential storage reservoirs and confining layers at the premier CO2 geological storage site in Wyoming. An accurate site characterization was essential to assessing the following critical aspects of the storage site: (1) more accurately estimate the CO2 reservoir storage capacity (Madison Limestone and Weber Sandstone at the Rock Springs Uplift (RSU)), (2) evaluate the distribution, long-term integrity, and permanence of the confining layers, (3) manage CO2 injection pressures by removing formation fluids (brine production/treatment), and (4) evaluate potential utilization of the stored CO2

  2. Compressive sensing-based wideband capacitance measurement with a fixed sampling rate lower than the highest exciting frequency

    International Nuclear Information System (INIS)

    Xu, Lijun; Ren, Ying; Sun, Shijie; Cao, Zhang

    2016-01-01

    In this paper, an under-sampling method for wideband capacitance measurement was proposed by using the compressive sensing strategy. As the excitation signal is sparse in the frequency domain, the compressed sampling method that uses a random demodulator was adopted, which could greatly decrease the sampling rate. Besides, four switches were used to replace the multiplier in the random demodulator. As a result, not only the sampling rate can be much smaller than the signal excitation frequency, but also the circuit’s structure is simpler and its power consumption is lower. A hardware prototype was constructed to validate the method. In the prototype, an excitation voltage with a frequency up to 200 kHz was applied to a capacitance-to-voltage converter. The output signal of the converter was randomly modulated by a pseudo-random sequence through four switches. After a low-pass filter, the signal was sampled by an analog-to-digital converter at a sampling rate of 50 kHz, which was three times lower than the highest exciting frequency. The frequency and amplitude of the signal were then reconstructed to obtain the measured capacitance. Both theoretical analysis and experiments were carried out to show the feasibility of the proposed method and to evaluate the performance of the prototype, including its linearity, sensitivity, repeatability, accuracy and stability within a given measurement range. (paper)

  3. [Archivos de Bronconeumología: among the 3 Spanish medical journals with the highest national impact factors].

    Science.gov (United States)

    Aleixandre Benavent, R; Valderrama Zurián, J C; Castellano Gómez, M; Simó Meléndez, R; Navarro Molina, C

    2004-12-01

    Citation analysis elucidates patterns of information consumption within professional communities. The aim of this study was to analyze the citations of 87 Spanish medical journals by calculating their impact factors and immediacy indices for 2001, and to estimate the importance of Archivos de Bronconeumología within the framework of Spanish medicine. Eighty-seven Spanish medical journals were included. All were listed in the Spanish Medical Index (Indice Medico Español) and in at least one of the following databases: MEDLINE, BIOSIS, EMBASE, or Science Citation Index. References to articles from 1999 through 2001 in citable articles from 2001 were analyzed. Using the method of the Institute for Scientific Information, we calculated the national impact factor and immediacy index for each journal. The journals with the highest national impact factors were Revista Española de Quimioterapia (0.894), Medicina Clínica (0.89), and Archivos de Bronconeumología (0.732). The self-citation percentage of Archivos de Bronconeumología was 18.3% and the immediacy index was 0.033. The impact factor obtained by Archivos de Bronconeumología confirms its importance in Spanish medicine and validates its inclusion as a source journal in Science Citation Index and Journal Citation Report.

  4. The Risk of Reported Cryptosporidiosis in Children Aged <5 Years in Australia is Highest in Very Remote Regions.

    Science.gov (United States)

    Lal, Aparna; Fearnley, Emily; Kirk, Martyn

    2015-09-18

    The incidence of cryptosporidiosis is highest in children <5 years, yet little is known about disease patterns across urban and rural areas of Australia. In this study, we examine whether the risk of reported cryptosporidiosis in children <5 years varies across an urban-rural gradient, after controlling for season and gender. Using Australian data on reported cryptosporidiosis from 2001 to 2012, we spatially linked disease data to an index of geographic remoteness to examine the geographic variation in cryptosporidiosis risk using negative binomial regression. The Incidence Risk Ratio (IRR) of reported cryptosporidiosis was higher in inner regional (IRR 1.4 95% CI 1.2-1.7, p < 0.001), and outer regional areas (IRR 2.4 95% CI 2.2-2.9, p < 0.001), and in remote (IRR 5.2 95% CI 4.3-6.2, p < 0.001) and very remote (IRR 8.2 95% CI 6.9-9.8, p < 0.001) areas, compared to major cities. A linear test for trend showed a statistically significant trend with increasing remoteness. Remote communities need to be a priority for future targeted health promotion and disease prevention interventions to reduce cryptosporidiosis in children <5 years.

  5. The Risk of Reported Cryptosporidiosis in Children Aged <5 Years in Australia is Highest in Very Remote Regions

    Directory of Open Access Journals (Sweden)

    Aparna Lal

    2015-09-01

    Full Text Available The incidence of cryptosporidiosis is highest in children <5 years, yet little is known about disease patterns across urban and rural areas of Australia. In this study, we examine whether the risk of reported cryptosporidiosis in children <5 years varies across an urban-rural gradient, after controlling for season and gender. Using Australian data on reported cryptosporidiosis from 2001 to 2012, we spatially linked disease data to an index of geographic remoteness to examine the geographic variation in cryptosporidiosis risk using negative binomial regression. The Incidence Risk Ratio (IRR of reported cryptosporidiosis was higher in inner regional (IRR 1.4 95% CI 1.2–1.7, p < 0.001, and outer regional areas (IRR 2.4 95% CI 2.2–2.9, p < 0.001, and in remote (IRR 5.2 95% CI 4.3–6.2, p < 0.001 and very remote (IRR 8.2 95% CI 6.9–9.8, p < 0.001 areas, compared to major cities. A linear test for trend showed a statistically significant trend with increasing remoteness. Remote communities need to be a priority for future targeted health promotion and disease prevention interventions to reduce cryptosporidiosis in children <5 years.

  6. Solving The Longstanding Problem Of Low-Energy Nuclear Reactions At the Highest Microscopic Level - Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Quaglioni, S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-09-22

    A 2011 DOE-NP Early Career Award (ECA) under Field Work Proposal (FWP) SCW1158 supported the project “Solving the Long-Standing Problem of Low-Energy Nuclear Reactions at the Highest Microscopic Level” in the five-year period from June 15, 2011 to June 14, 2016. This project, led by PI S. Quaglioni, aimed at developing a comprehensive and computationally efficient framework to arrive at a unified description of structural properties and reactions of light nuclei in terms of constituent protons and neutrons interacting through nucleon-nucleon (NN) and three-nucleon (3N) forces. Specifically, the project had three main goals: 1) arriving at the accurate predictions for fusion reactions that power stars and Earth-based fusion facilities; 2) realizing a comprehensive description of clustering and continuum effects in exotic nuclei, including light Borromean systems; and 3) achieving fundamental understanding of the role of the 3N force in nuclear reactions and nuclei at the drip line.

  7. Two Clock Transitions in Neutral Yb for the Highest Sensitivity to Variations of the Fine-Structure Constant

    Science.gov (United States)

    Safronova, Marianna S.; Porsev, Sergey G.; Sanner, Christian; Ye, Jun

    2018-04-01

    We propose a new frequency standard based on a 4 f146 s 6 p P0 3 -4 f136 s25 d (J =2 ) transition in neutral Yb. This transition has a potential for high stability and accuracy and the advantage of the highest sensitivity among atomic clocks to variation of the fine-structure constant α . We find its dimensionless α -variation enhancement factor to be K =-15 , in comparison to the most sensitive current clock (Yb+ E 3 , K =-6 ), and it is 18 times larger than in any neutral-atomic clocks (Hg, K =0.8 ). Combined with the unprecedented stability of an optical lattice clock for neutral atoms, this high sensitivity opens new perspectives for searches for ultralight dark matter and for tests of theories beyond the standard model of elementary particles. Moreover, together with the well-established 1S0-3P0 transition, one will have two clock transitions operating in neutral Yb, whose interleaved interrogations may further reduce systematic uncertainties of such clock-comparison experiments.

  8. Impacts of informal trails on vegetation and soils in the highest protected area in the Southern Hemisphere.

    Science.gov (United States)

    Barros, Agustina; Gonnet, Jorge; Pickering, Catherine

    2013-09-30

    There is limited recreation ecology research in South America, especially studies looking at informal trails. Impacts of informal trails formed by hikers and pack animals on vegetation and soils were assessed for the highest protected area in the Southern Hemisphere, Aconcagua Provincial Park. The number of braided trails, their width and depth were surveyed at 30 sites along the main access route to Mt Aconcagua (6962 m a.s.l.). Species composition, richness and cover were also measured on control and trail transects. A total of 3.3 ha of alpine meadows and 13.4 ha of alpine steppe were disturbed by trails. Trails through meadows resulted in greater soil loss, more exposed soil and rock and less vegetation than trails through steppe vegetation. Trampling also affected the composition of meadow and steppe vegetation with declines in sedges, herbs, grasses and shrubs on trails. These results highlight how visitor use can result in substantial cumulative damage to areas of high conservation value in the Andes. With unregulated use of trails and increasing visitation, park agencies need to limit the further spread of informal trails and improve the conservation of plant communities in Aconcagua Provincial Park and other popular parks in the region. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Diclofenac affects kidney histology in the three-spined stickleback (Gasterosteus aculeatus) at low μg/L concentrations.

    Science.gov (United States)

    Näslund, Johanna; Fick, Jerker; Asker, Noomi; Ekman, Elisabet; Larsson, D G Joakim; Norrgren, Leif

    2017-08-01

    Diclofenac, a commonly used non-steroidal anti-inflammatory drug, is considered for regulation under the European water framework directive. This is because effects on fish have been reported at concentrations around those regularly found in treated sewage effluents (∼1μg/L). However, a recent publication reports no effects on fish at 320μg/L. In this study, three-spined sticklebacks (Gasterosteus aculeatus) were exposed to 0, 4.6, 22, 82 and 271μg/L diclofenac in flow-through systems for 28days using triplicate aquaria per concentration. At the highest concentration, significant mortalities were observed already after 21days (no mortalities found up to 22μg/L). Histological analysis revealed a significant increase in the proportion of renal hematopoietic tissue (renal hematopoietic hyperplasia) after 28days at the lowest concentration and at all higher concentrations, following a clear dose-response pattern. Skin ulcerations of the jaw were noted by macroscopic observations, primarily at the two highest concentrations. No histological changes were observed in the liver. There was an increase in the relative hepatic mRNA levels of c7 (complement component 7), a gene involved in the innate immune system, at 22μg/L and at all higher concentrations, again following a clear dose-response. The bioconcentration factor was stable across concentrations, but lower than reported for rainbow trout, suggesting lower internal exposure to the drug in the stickleback. In conclusion, this study demonstrates that diclofenac causes histological changes in the three-spined stickleback at low μg/L concentrations, which cause concern for fish populations exposed to treated sewage effluents. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. [Drugs and occupational accident].

    Science.gov (United States)

    Bratzke, H; Albers, C

    1996-02-01

    In a case of a fatal occupational accident (construction worker, fall from roof, urine test positive for cocaine and THC, e.g. cannabis) the question arised to what extent those drug-related occupational accidents occur. In the literature only few cases, mainly dealing with cannabis influence, have been reported, however, a higher number is suspected. Cocaine and other stimulating drugs (amphetamine) are more often used to increase physical fitness. By direct or indirect interference with vigilance these compounds may provoke accidents. Due to the lack of a legal basis proving of the influence of drugs at the working place is still very limited, although highly sensitive chemical-toxicological assay procedures are available to detect even the chronic abuse (in hair). In the general conditions of accident insurances a compensation is excluded when alcohol is involved, but drugs are not mentioned. It is indeed difficult to establish a concentration limit for drugs like that existing for alcohol (1.1%). In each case the assay of the drug involved and exact knowledge of its specific effects is in an essential prerequisite to prove the causal relationship.

  11. A story about the discovery of the largest glacier and the highest peak in heart of the Pamirs

    Directory of Open Access Journals (Sweden)

    V. M. Kotlyakov

    2014-01-01

    Full Text Available The paper tells a story how the “blank spot” at the Pamirs center was puzzled out. In 1878, a small party of explorers headed by V.D. Oshanin had found here a big glacier about 30–40 km long and named it for Fedchenko. In 1884–85, known investigator G.E. Grumm-Grzhimailo made his important proposal about orographic structure of the Pamirs central part. In 1890, expedition headed by topographer N.I. Kosinenko investigated the lower part of the Fedchenko Glacier and, for the first time, saw a separate high peak. In 1916, astronomer Ya.I. Belyaev had put on a map a great pyramidal summit but he had mistaken it for the Garmo Peak well known to local Tadzhiks (Fig. 2.In 1927, N.L. Korzhenevsky published a chart of arrangement of ridges near sources of the river Muksu (Fig. 3 that became a basis for work of the Tadzhik-Pamir expedition of 1928–1932. In 1928, Ya.I. Belyaev determined a true length of the Fechenko Glacier that was 70 km, and geodesist I.G. Dorofeevmapped the whole basin of this glacier (Fig. 4 including also a high irregular truncated pyramid of 7495 m in height (as he believed. But earlier this summit was identified as known the Garmo Peak. And only in 1932, it was established that definitions made by Dorofeev in 1928 were related to this highest peak of the Pamirs and also of the whole Soviet Union. The chart of real Central Pamir orography constructed by I.G. Dorofeev is presented in the paper together with his letter addressed to the author (Fig. 5.Thus, the “Garmo peaks” which were observed by the above mentioned explorers were actually three different summits. One of them does tower on the north of the “knot being puzzled out” and reaches 7495 m, and namely this “one-tooth” peak was repeatedly seen by N.V. Krylenko from valleys Gando and Garmo. It was named then the Stalin peak, and later – the peak of Communism. Another one is located in 18 km southward, and this peak is actually the true Garmo Peak 6595 m

  12. Binding of higher alcohols onto Mn(12) single-molecule magnets (SMMs): access to the highest barrier Mn(12) SMM.

    Science.gov (United States)

    Lampropoulos, Christos; Redler, Gage; Data, Saiti; Abboud, Khalil A; Hill, Stephen; Christou, George

    2010-02-15

    Two new members of the Mn(12) family of single-molecule magnets (SMMs), [Mn(12)O(12)(O(2)CCH(2)Bu(t))(16)(Bu(t)OH)(H(2)O)(3)].2Bu(t)OH (3.2Bu(t)OH) and [Mn(12)O(12)(O(2)CCH(2)Bu(t))(16)(C(5)H(11)OH)(4)] (4) (C(5)H(11)OH is 1-pentanol), are reported. They were synthesized from [Mn(12)O(12)(O(2)CMe)(16)(H(2)O)(4)].2MeCO(2)H.4H(2)O (1) by carboxylate substitution and crystallization from the appropriate alcohol-containing solvent. Complexes 3 and 4 are new members of the recently established [Mn(12)O(12)(O(2)CCH(2)Bu(t))(16)(solv)(4)] (solv = H(2)O, alcohols) family of SMMs. Only one bulky Bu(t)OH can be accommodated into 3, and even this causes significant distortion of the [Mn(12)O(12)] core. Variable-temperature, solid-state alternating current (AC) magnetization studies were carried out on complexes 3 and 4, and they established that both possess an S = 10 ground state spin and are SMMs. However, the magnetic behavior of the two compounds was found to be significantly different, with 4 showing out-of-phase AC peaks at higher temperatures than 3. High-frequency electron paramagnetic resonance (HFEPR) studies were carried out on single crystals of 3.2Bu(t)OH and 4, and these revealed that the axial zero-field splitting constant, D, is very different for the two compounds. Furthermore, it was established that 4 is the Mn(12) SMM with the highest kinetic barrier (U(eff)) to date. The results reveal alcohol substitution as an additional and convenient means to affect the magnetization relaxation barrier of the Mn(12) SMMs without major change to the ligation or oxidation state.

  13. Investigation of Behçet's Disease and Recurrent Aphthous Stomatitis Frequency: The Highest Prevalence in Turkey

    Directory of Open Access Journals (Sweden)

    Yalçın Baş

    2016-08-01

    Full Text Available Background: The Recurrent Aphthous Stomatitis (RAS is the most frequently observed painful pathology of the oral mucosa in the society. It appears mostly in idiopathic form; however, it may also be related with systemic diseases like Behçet’s Disease (BD. Aims: Determining the prevalence of RAS and BD in the Northern Anatolian Region, which is one of the important routes on the Antique Silk Road. Study Design: Cross-sectional study. Methods: Overall, 85 separate exemplification groups were formed to reflect the population density, and the demographic data of the region they represent. In the first stage, the individuals, who were selected in random order, were invited to a Family Physician Unit at a certain date and time. The dermatological examinations of the volunteering individuals were performed by only 3 dermatology specialists. In the second stage, those individuals who had symptoms of BD were invited to our hospital, and the Pathergy Test and eye examinations were performed. Results: The annual prevalence of RAS was determined as 10.84%. The annual prevalence was determined to be higher in women than in men (p=0.000. It was observed that the prevalence was at the peak level in the 3rd decade, and then decreased proportionally in the following decades (p=0.000. It was also observed that the aphtha recurrence decreased in the following decades (p=0.048. The Behçet’s prevalence was found to be 0.60%. The prevalence in women was found to be higher than in men (0.86% female, 0.14% male; p=0.022. Conclusion: While the RAS prevalence ratio was at an average value when compared with the other societies; the BD prevalence was found as the highest ratio in the world according to the literature.

  14. Where do the highest energy CR's come from? and How does the Milky Way affect their arrival directions?

    Directory of Open Access Journals (Sweden)

    Kronberg Philipp

    2013-06-01

    Full Text Available A “grand magnetic design” for the Milky Way disk clearly emerges within ~1.5 kpc of the Galactic mid-plane near the Sun [1], and reveals a pitch angle of −5.5°. directed inward from the Solar tangential. This pitch angle can be expected to differ for Galactic disc locations other than ours. Above ~1.5 kpc, the field geometry is completely different, and its 3-D structure is not yet completely specified. However it appears that the UHECR (> 5 · 1019 eV propagation to us is not much affected by the halo field, at least for protons. I discuss new multi-parameter analyses of UHECR deflections which provide a conceptual “template” for future interpretations of energy-species-direction data from AUGER, HiRes etc., and their successors [2]. I show how the strength and structure of the cosmologically nearby intergalactic magnetic field, BIGM, is now well-estimated out to D ~5 Mpc from the Milky Way: − 20nG. These are the first VHECR data-based estimates of BIGM on nearby supragalactic scales, and are also important for understanding and modeling CR propagation in the more distant Universe. CR Acceleration to the highest energies is probably a natural accompanying phenomenon of Supermassive Black Hole (SMBH-associated jets and lobes [3]. I briefly describe what we know about magnetic configurations in these candidate sites for UHECR acceleration, and the first direct estimate of an extragalactic Poynting flux current, ~3 · 1018 Amperes [4, 5]. This number connects directly to SMBH accretion disk physics, and leads directly to ideas of how VHECR acceleration in jets and lobes, possibly involving magnetic reconnection, is likely to be common in the Universe. It remains to be fully understood.

  15. Identification of multiple sclerosis patients at highest risk of cognitive impairment using an integrated brain magnetic resonance imaging assessment approach.

    Science.gov (United States)

    Uher, T; Vaneckova, M; Sormani, M P; Krasensky, J; Sobisek, L; Dusankova, J Blahova; Seidl, Z; Havrdova, E; Kalincik, T; Benedict, R H B; Horakova, D

    2017-02-01

    While impaired cognitive performance is common in multiple sclerosis (MS), it has been largely underdiagnosed. Here a magnetic resonance imaging (MRI) screening algorithm is proposed to identify patients at highest risk of cognitive impairment. The objective was to examine whether assessment of lesion burden together with whole brain atrophy on MRI improves our ability to identify cognitively impaired MS patients. Of the 1253 patients enrolled in the study, 1052 patients with all cognitive, volumetric MRI and clinical data available were included in the analysis. Brain MRI and neuropsychological assessment with the Brief International Cognitive Assessment for Multiple Sclerosis were performed. Multivariable logistic regression and individual prediction analysis were used to investigate the associations between MRI markers and cognitive impairment. The results of the primary analysis were validated at two subsequent time points (months 12 and 24). The prevalence of cognitive impairment was greater in patients with low brain parenchymal fraction (BPF) (3.5 ml) than in patients with high BPF (>0.85) and low T2-LV (patients predicted cognitive impairment with 83% specificity, 82% negative predictive value, 51% sensitivity and 75% overall accuracy. The risk of confirmed cognitive decline over the follow-up was greater in patients with high T2-LV (OR 2.1; 95% CI 1.1-3.8) and low BPF (OR 2.6; 95% CI 1.4-4.7). The integrated MRI assessment of lesion burden and brain atrophy may improve the stratification of MS patients who may benefit from cognitive assessment. © 2016 EAN.

  16. Lyman alpha emission in nearby star-forming galaxies with the lowest metallicities and the highest [OIII]/[OII] ratios

    Science.gov (United States)

    Izotov, Yuri

    2017-08-01

    The Lyman alpha line of hydrogen is the strongest emission line in galaxies and the tool of predilection for identifying and studying star-forming galaxies over a wide range of redshifts, especially in the early universe. However, it has become clear over the years that not all of the Lyman alpha radiation escapes, due to its resonant scattering on the interstellar and intergalactic medium, and absorption by dust. Although our knowledge of the high-z universe depends crucially on that line, we still do not have a complete understanding of the mechanisms behind the production, radiative transfer and escape of Lyman alpha in galaxies. We wish here to investigate these mechanisms by studying the properties of the ISM in a unique sample of 8 extreme star-forming galaxies (SFGs) that have the highest excitation in the SDSS spectral data base. These dwarf SFGs have considerably lower stellar masses and metallicities, and higher equivalent widths and [OIII]5007/[OII]3727 ratios compared to all nearby SFGs with Lyman alpha emission studied so far with COS. They are, however, very similar to the dwarf Lyman alpha emitters at redshifts 3-6, which are thought to be the main sources of reionization in the early Universe. By combining the HST/COS UV data with data in the optical range, and using photoionization and radiative transfer codes, we will be able to study the properties of the Lyman alpha in these unique objects, derive column densities of the neutral hydrogen N(HI) and compare them with N(HI) obtained from the HeI emission-line ratios in the optical spectra. We will derive Lyman alpha escape fractions and indirectly Lyman continuum escape fractions.

  17. Can All Doctors Be Like This? Seven Stories of Communication Transformation Told by Physicians Rated Highest by Patients.

    Science.gov (United States)

    Janisse, Tom; Tallman, Karen

    2017-01-01

    The top predictors of patient satisfaction with clinical visits are the quality of the physician-patient relationship and the communications contributing to their relationship. How do physicians improve their communication, and what effect does it have on them? This article presents the verbatim stories of seven high-performing physicians describing their transformative change in the areas of communication, connection, and well-being. Data for this study are based on interviews from a previous study in which a 6-question set was posed, in semistructured 60-minute interviews, to 77 of the highest-performing Permanente Medical Group physicians in 4 Regions on the "Art of Medicine" patient survey. Transformation stories emerged spontaneously during the interviews, and so it was an incidental finding when some physicians identified that they were not always high performing in their communication with patients. Seven different modes of transformation in communication were described by these physicians: a listening tool, an awareness course, finding new meaning in clinical practice, a technologic tool, a sudden insight, a mentor observation, and a physician-as-patient experience. These stories illustrate how communication skills can be learned through various activities and experiences that transform physicians into those who are highly successful communicators. All modes result in a change of state-a new way of seeing, of being-and are not just a new tool or a new practice, but a change in state of mind. This state resulted in a marked change of behavior, and a substantial improvement of communication and relationship.

  18. 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.

  19. [Club drugs].

    Science.gov (United States)

    Guerreiro, Diogo Frasquilho; Carmo, Ana Lisa; da Silva, Joaquim Alves; Navarro, Rita; Góis, Carlos

    2011-01-01

    Club drugs are the following substances: Methylenedioxymethamphetamine (MDMA); Methamphetamine; Lysergic Acid Diethylamide (LSD); Ketamine; Gamma-hydroxybutyrate (GHB) and Flunitrazepam. These substances are mainly used by adolescents and young adults, mostly in recreational settings like dance clubs and rave parties. These drugs have diverse psychotropic effects, are associated with several degrees of toxicity, dependence and long term adverse effects. Some have been used for several decades, while others are relatively recent substances of abuse. They have distinct pharmacodynamic and pharmacokinetic properties, are not easy to detect and, many times, the use of club drugs is under diagnosed. Although the use of these drugs is increasingly common, few health professionals feel comfortable with the diagnosis and treatment. The authors performed a systematic literature review, with the goal of synthesising the existing knowledge about club drugs, namely epidemiology, mechanism of action, detection, adverse reactions and treatment. The purpose of this article is creating in Portuguese language a knowledge data base on club drugs, that health professionals of various specialties can use as a reference when dealing with individual with this kind of drug abuse.

  20. Emerging Frontiers in Drug Delivery.

    Science.gov (United States)

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

    2016-01-27

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

  1. Plasma concentrations of misonidazole

    Energy Technology Data Exchange (ETDEWEB)

    Notter, G; Rylander, U; Turesson, I

    1980-10-01

    The plasma concentrations of misonidazole doses between 0.6 and 2.0 g/m/sup 2/ were analyzed in respect to the variation within the same patient and between different patients. Peak plasma levels were observed after 2 hours. The mean plasma levels of misonidazole only at 3 hours were 23.8, 47.0 and 76.5 ..mu..g/ml after misonidazole doses of 0.6, 1.2 g/m/sup 2/, respectively. The half-life of misonidazole only was found to be 8.2 hours for women and 10.5 for men. Good linearity between plasma levels and drug doses was observed after administration of different single doses to the same patient within the dose range 0.6 to 2.0 g/m/sup 2/.

  2. Desktop analysis of potential impacts of visitor use: a case study for the highest park in the Southern Hemisphere.

    Science.gov (United States)

    Barros, Agustina; Pickering, Catherine; Gudes, Ori

    2015-03-01

    Nature-based tourism and recreation activities have a range of environmental impacts, but most protected area agencies have limited capacity to assess them. To prioritise where and what impacts to monitor and manage, we conducted a desktop assessment using Geographical Information Systems (GIS) by combining recreation ecology research with data on visitor usage and key environmental features for a popular protected area used for mountaineering and trekking, Aconcagua Provincial Park (2400-6962 m a.s.l.) in the Andes of Argentina. First, we integrated visitor data from permits with environmental data using GIS. We then identified key impact indicators for different activities based on the recreation ecology literature. Finally, we integrated this data to identify likely ecological impacts based on the types of activities, amount of use and altitudinal zones. Visitors only used 2% of the Park, but use was concentrated in areas of high conservation value including in alpine meadows and glacier lakes. Impacts on water resources were likely to be concentrated in campsites from the intermediate to the nival/glacial zones of the Park while impacts on terrestrial biodiversity were likely to be more severe in the low and intermediate alpine zones (2400-3800 m a.s.l.). These results highlight how visitor data can be used to identify priority areas for on-ground assessment of impacts in key locations. Improvements to the management of visitors in this Park involves more effective ways of dealing with water extraction and human waste in high altitude campsites and the impacts of hikers and pack animals in the low and intermediate alpine zones. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Time of highest tuberculosis death risk and associated factors: an observation of 12 years in Northern Thailand

    Directory of Open Access Journals (Sweden)

    Saiyud Moolphate

    2011-02-01

    Full Text Available Saiyud Moolphate1,2, Myo Nyein Aung1,3, Oranuch Nampaisan1, Supalert Nedsuwan4, Pacharee Kantipong5, Narin Suriyon6, Chamnarn Hansudewechakul6, Hideki Yanai7, Norio Yamada2, Nobukatsu Ishikawa21TB/HIV Research Foundation, Chiang Rai, Thailand; 2Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association (RIT-JATA, Tokyo, Japan; 3Department of Pharmacology, University of Medicine, Mandalay, Myanmar; 4Department of Preventive and Social Medicine, Chiang Rai Regional Hospital, Chiang Rai, Thailand; 5Department of Health Service System Development, Chiang Rai Regional Hospital, Chiang Rai, Thailand; 6Provincial Health Office, Chiang Rai, Thailand; 7Department of Clinical Laboratory, Fukujuji Hospital, Tokyo, JapanPurpose: Northern Thailand is a tuberculosis (TB endemic area with a high TB death rate. We aimed to establish the time of highest death risk during TB treatment, and to identify the risk factors taking place during that period of high risk.Patients and methods: We explored the TB surveillance data of the Chiang Rai province, Northern Thailand, retrospectively for 12 years. A total of 19,174 TB patients (including 5,009 deaths were investigated from 1997 to 2008, and the proportion of deaths in each month of TB treatment was compared. Furthermore, multiple logistic regression analysis was performed to identify the characteristics of patients who died in the first month of TB treatment. A total of 5,626 TB patients from 2005 to 2008 were included in this regression analysis.Result: The numbers of deaths in the first month of TB treatment were 38%, 39%, and 46% in the years 1997–2000, 2001–2004, and 2005–2008, respectively. The first month of TB treatment is the time of the maximum number of deaths. Moreover, advancing age, HIV infection, and being a Thai citizen were significant factors contributing to these earlier deaths in the course of TB treatment.Conclusion: Our findings have pointed to the specific time period and

  4. Drug Facts

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  5. Drug Facts

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  6. Drug Facts

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  7. Drug Facts

    Medline Plus

    Full Text Available ... Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain ... About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other ...

  8. Drug Metabolism

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 3. Drug Metabolism: A Fascinating Link Between Chemistry and Biology. Nikhil Taxak Prasad V Bharatam. General Article Volume 19 Issue 3 March 2014 pp 259-282 ...

  9. Drugged Driving

    Science.gov (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  10. Club Drugs

    Science.gov (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  11. Drug Metabolism

    Indian Academy of Sciences (India)

    IAS Admin

    behind metabolic reactions, importance, and consequences with several ... required for drug action. ... lism, which is catalyzed by enzymes present in the above-men- ... catalyze the transfer of one atom of oxygen to a substrate produc-.

  12. Drug Facts

    Medline Plus

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

  13. Drug Facts

    Medline Plus

    Full Text Available ... 800-662-HELP (4357) at any time to find drug treatment centers near you. I want my ... is making positive changes in her life. She finds support from family and friends who don't ...

  14. Drug Facts

    Medline Plus

    Full Text Available ... That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, ... Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) ...

  15. Drug Facts

    Medline Plus

    Full Text Available ... Together The Link Between Drug Use and HIV/AIDS Treatment & Recovery Why Does a Person Need Treatment? ... of Health (NIH) , the principal biomedical and behavioral research agency of the United States Government. NIH is ...

  16. Drug Reactions

    Science.gov (United States)

    ... Kids and Teens Pregnancy and Childbirth Women Men Seniors Your Health Resources Healthcare Management End-of-Life Issues Insurance & Bills Self Care Working With Your Doctor Drugs, Procedures & Devices Over-the- ...

  17. Drug Facts

    Medline Plus

    Full Text Available ... prescription drugs. The addiction slowly took over his life. I need different people around me. To stop ... marijuana, "Cristina" is making positive changes in her life. She finds support from family and friends who ...

  18. Drug Resistance

    Science.gov (United States)

    ... Drug-resistance testing is also recommended for all pregnant women with HIV before starting HIV medicines and also in some pregnant women already taking HIV medicines. Pregnant women will work with their health ...

  19. Drug Facts

    Medline Plus

    Full Text Available ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine ...

  20. Drug Addiction

    Science.gov (United States)

    ... as hearing colors Impulsive behavior Rapid shifts in emotions Permanent mental changes in perception Rapid heart rate ... Drug use can negatively affect academic performance and motivation to excel in school. Legal issues. Legal problems ...

  1. Drug Facts

    Medline Plus

    Full Text Available ... That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana ( ... Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) ...

  2. Toxins and drug discovery.

    Science.gov (United States)

    Harvey, Alan L

    2014-12-15

    Components from venoms have stimulated many drug discovery projects, with some notable successes. These are briefly reviewed, from captopril to ziconotide. However, there have been many more disappointments on the road from toxin discovery to approval of a new medicine. Drug discovery and development is an inherently risky business, and the main causes of failure during development programmes are outlined in order to highlight steps that might be taken to increase the chances of success with toxin-based drug discovery. These include having a clear focus on unmet therapeutic needs, concentrating on targets that are well-validated in terms of their relevance to the disease in question, making use of phenotypic screening rather than molecular-based assays, and working with development partners with the resources required for the long and expensive development process. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

  3. Enhanced drug delivery capabilities from stents coated with absorbable polymer and crystalline drug

    OpenAIRE

    Carlyle, Wenda C.; McClain, James B.; Tzafriri, Abraham R.; Bailey, Lynn; Zani, Brett G.; Markham, Peter M.; Stanley, James R.L.; Edelman, Elazer R.

    2012-01-01

    Current drug eluting stent (DES) technology is not optimized with regard to the pharmacokinetics of drug delivery. A novel, absorbable-coating sirolimus-eluting stent (AC-SES) was evaluated for its capacity to deliver drug more evenly within the intimal area rather than concentrating drug around the stent struts and for its ability to match coating erosion with drug release. The coating consisted of absorbable poly-lactide-co-glycolic acid (PLGA) and crystalline sirolimus deposited by a dry-p...

  4. Aerosol deposition (trace elements and black carbon) over the highest glacier of the Eastern European Alps during the last centuries

    Science.gov (United States)

    Bertò, Michele; Barbante, Carlo; Gabrieli, Jacopo; Gabrielli, Paolo; Spolaor, Andrea; Dreossi, Giuliano; Laj, Paolo; Zanatta, Marco; Ginot, Patrick; Fain, Xavier

    2016-04-01

    Ice cores are an archive of a wide variety of climatic and environmental information from the past, retaining them for hundreds of thousands of years. Anthropogenic pollutants, trace elements, heavy metals and major ions, are preserved as well providing insights on the past atmospheric circulations and allowing evaluating the human impact on the environment. Several ice cores were drilled in glaciers at mid and low latitudes, as in the European Alps. The first ice cores drilled to bedrock in the Eastern Alps were retrieved during autumn 2011 on the "Alto dell`Ortles glacier", the uppermost glacier of the Ortles massif (3905m, South Tirol, Italy), in the frame of the "Ortles Project". A preliminary dating of the core suggests that it should cover at least 300-400 years. Despite the summer temperature increase of the last decades this glacier still contain cold ice. Indeed, O and H isotopes profiles well describe the atmospheric warming as well as the low temperatures recorded during the Little Ice Age (LIA). Moreover, this glacier is located close to densely populated and industrialized areas and can be used for reconstructing for the first time past and recent air pollution and the human impact in the Eastern European Alps. The innermost part of the core is under analysis by means of a "Continuous Flow Analysis" system. This kind of analysis offers a high resolution in data profiles. The separation between the internal and the external parts of the core avoid any kind of contamination. An aluminum melting head melts the core at about 2.5 cm min-1. Simultaneous analyses of conductivity, dust concentration and size distribution (from 0.8 to 80 μm), trace elements with Inductive Coupled Plasma Mass Spectrometer (ICP-MS, Agilent 7500) and refractory black carbon (rBC) with the Single Particle Soot Photometer (SP2, Droplet Measurement Technologies) are performed. A fraction of the melt water is collected by an auto-sampler for further analysis. The analyzed elements

  5. Reversible pH-Sensitive Chitosan-Based Hydrogels. Influence of Dispersion Composition on Rheological Properties and Sustained Drug Delivery

    Directory of Open Access Journals (Sweden)

    Nieves Iglesias

    2018-04-01

    Full Text Available The present work deals with the synthesis of micro-structured biomaterials based on chitosan (CTS for their applications as biocompatible carriers of drugs and bioactive compounds. Twelve dispersions were prepared by means of functional cross-linking with tricarballylic acid (TCA; they were characterized by Fourier transform infrared spectroscopy (FT-IR, modulated temperature differential scanning calorimetry (MTDSC and scanning electron microscopy (SEM, and their rheological properties were studied. To the best of the authors’ knowledge, no study has been carried out on the influence of CTS concentration, degree of cross-linking and drug loading on chitosan hydrogels for drug delivery systems (DDS and is investigated herein for the first time. The influence of dispersion composition (polymer concentration and degree of cross-linking revealed to exert a marked impact on its rheological properties, going from liquid-like to viscoelastic gels. The release profiles of a model drug, diclofenac sodium (DCNa, as well as their relationships with polymer concentration, drug loading and degree of cross-linking were evaluated. Similar to the findings on rheological properties, a wide range of release profiles was encountered. These formulations were found to display a well-controlled drug release strongly dependent on the formulation composition. Cumulative drug release under physiological conditions for 96 h ranged from 8% to 67%. For comparative purpose, Voltaren emulgel® from Novartis Pharmaceuticals was also investigated and the latter was the formulation with the highest cumulative drug release (85%. Some formulations showed similar spreadability values to the commercial hydrogel. The comparative study of three batches confirmed the reproducibility of the method, leading to systems particularly suitable for their use as drug carriers.

  6. The use of drugs and medicines behind the wheel. [Previously called Driving under the influence of drugs and medicines.

    NARCIS (Netherlands)

    2009-01-01

    Research shows that about 4% of drivers in Europe participate in traffic after having taken drugs and/or medicines. With 3.4% this share was lower in the Netherlands; traces of drugs were found in approximately 2.8% of the car drivers and traces of drugs were found in 0.6%. Substance use is highest

  7. Impact of common cytostatic drugs on pollen fertility in higher plants.

    Science.gov (United States)

    Mišík, Miroslav; Kundi, Michael; Pichler, Clemens; Filipic, Metka; Rainer, Bernhard; Mišíková, Katarina; Nersesyan, Armen; Knasmueller, Siegfried

    2016-08-01

    Cytostatic drugs are among the most toxic chemicals which are produced. Many of them cause damage of the genetic material which may affect the fertility of higher organisms. To study the impact of the widely used anticancer drugs [cisplatin (CisPt), etoposide (Et), and 5-fluorouracil (5-FU)] on the reproduction of higher plants, pollen abortion experiments were conducted with species which belong to major plant families, namely with Tradescantia paludosa (Commelinaceae), Arabidopsis thaliana (Brassicaceae), Chelidonium majus (Papaveraceae), and Alisma plantago-aquatica (Alismataceae). All compounds increased the frequencies of abortive grains. The lowest effective doses were in general in a narrow range (i.e., 1 and 10 mg/kg of dry soil). The effects of the individual drugs were similar in T. paludosa, A. plantago-aquatica, and Ch. majus, while A. thaliana was consistently less sensitive. The highest abortion rate was obtained in most experiments with CisPt, followed by 5-FU and Et. Comparisons of the doses which caused effects in the present experiments in the different species with the predicted environment concentrations and with the levels of the cytostatics which were detected in hospital wastewaters show that the realistic environmental concentrations of the drugs are 4-6 orders of magnitude lower. Therefore, it is unlikely that these drugs affect the fertility of higher plants in aquatic and terrestrial ecosystems.

  8. Quantifying metabolic heterogeneity in head and neck tumors in real time: 2-DG uptake is highest in hypoxic tumor regions.

    Directory of Open Access Journals (Sweden)

    Erica C Nakajima

    Full Text Available Intratumoral metabolic heterogeneity may increase the likelihood of treatment failure due to the presence of a subset of resistant tumor cells. Using a head and neck squamous cell carcinoma (HNSCC xenograft model and a real-time fluorescence imaging approach, we tested the hypothesis that tumors are metabolically heterogeneous, and that tumor hypoxia alters patterns of glucose uptake within the tumor.Cal33 cells were grown as xenograft tumors (n = 16 in nude mice after identification of this cell line's metabolic response to hypoxia. Tumor uptake of fluorescent markers identifying hypoxia, glucose import, or vascularity was imaged simultaneously using fluorescent molecular tomography. The variability of intratumoral 2-deoxyglucose (IR800-2-DG concentration was used to assess tumor metabolic heterogeneity, which was further investigated using immunohistochemistry for expression of key metabolic enzymes. HNSCC tumors in patients were assessed for intratumoral variability of (18F-fluorodeoxyglucose ((18F-FDG uptake in clinical PET scans.IR800-2-DG uptake in hypoxic regions of Cal33 tumors was 2.04 times higher compared to the whole tumor (p = 0.0001. IR800-2-DG uptake in tumors containing hypoxic regions was more heterogeneous as compared to tumors lacking a hypoxic signal. Immunohistochemistry staining for HIF-1α, carbonic anhydrase 9, and ATP synthase subunit 5β confirmed xenograft metabolic heterogeneity. We detected heterogeneous (18F-FDG uptake within patient HNSCC tumors, and the degree of heterogeneity varied amongst tumors.Hypoxia is associated with increased intratumoral metabolic heterogeneity. (18F-FDG PET scans may be used to stratify patients according to the metabolic heterogeneity within their tumors, which could be an indicator of prognosis.

  9. Postmortem Femoral Blood Concentrations of Risperidone

    DEFF Research Database (Denmark)

    Linnet, Kristian; Johansen, Sys Stybe

    2014-01-01

    Postmortem femoral blood concentrations of the antipsychotic drug risperidone and the active metabolite 9-hydroxyrisperidone were determined by an achiral LC-MS/MS method in 38 cases. The cause of death was classified as unrelated to risperidone in 30 cases, in which the sum of the concentration ...

  10. Legal Drugs Are Good Drugs and Illegal Drugs Are Bad Drugs

    OpenAIRE

    Indrati, Dina; Prasetyo, Herry

    2011-01-01

    ABSTRACT : Labelling drugs are important issue nowadays in a modern society. Although it is generally believed that legal drugs are good drugs and illegal drugs are bad drugs, it is evident that some people do not aware about the side effects of drugs used. Therefore, a key contention of this philosophical essay is that explores harms minimisation policy, discuss whether legal drugs are good drugs and illegal drugs are bad drugs and explores relation of drugs misuse in a psychiatric nursing s...

  11. Drugs@FDA: FDA Approved Drug Products

    Science.gov (United States)

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

  12. Study Drugs

    OpenAIRE

    Lam, Stephanie Phuong; Roosta, Natalie; Nielsen, Mikkel Fuhr; Meyer, Maria Holmgaard; Friis, Katrine Birk

    2016-01-01

    In recent years, students around the world, started to use preparations as Ritalin and Modafinil,also known as study drugs, to improve their cognitive abilities1. It is a common use among thestudents in United States of America, but it is a new tendency in Denmark. Our main focus is tolocate whether study drugs needs to be legalized in Denmark or not. To investigate this ourstarting point is to understand central ethical arguments in the debate. We have chosen twoarguments from Nick Bostrom a...

  13. Repurposing salicylanilide anthelmintic drugs to combat drug resistant Staphylococcus aureus.

    Science.gov (United States)

    Rajamuthiah, Rajmohan; Fuchs, Beth Burgwyn; Conery, Annie L; Kim, Wooseong; Jayamani, Elamparithi; Kwon, Bumsup; Ausubel, Frederick M; Mylonakis, Eleftherios

    2015-01-01

    Staphylococcus aureus is a Gram-positive bacterium that has become the leading cause of hospital acquired infections in the US. Repurposing Food and Drug Administration (FDA) approved drugs for antimicrobial therapy involves lower risks and costs compared to de novo development of novel antimicrobial agents. In this study, we examined the antimicrobial properties of two commercially available anthelmintic drugs. The FDA approved drug niclosamide and the veterinary drug oxyclozanide displayed strong in vivo and in vitro activity against methicillin resistant S. aureus (minimum inhibitory concentration (MIC): 0.125 and 0.5 μg/ml respectively; minimum effective concentration: ≤ 0.78 μg/ml for both drugs). The two drugs were also effective against another Gram-positive bacteria Enterococcus faecium (MIC 0.25 and 2 μg/ml respectively), but not against the Gram-negative species Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter aerogenes. The in vitro antimicrobial activity of niclosamide and oxyclozanide were determined against methicillin, vancomycin, linezolid or daptomycin resistant S. aureus clinical isolates, with MICs at 0.0625-0.5 and 0.125-2 μg/ml for niclosamide and oxyclozanide respectively. A time-kill study demonstrated that niclosamide is bacteriostatic, whereas oxyclozanide is bactericidal. Interestingly, oxyclozanide permeabilized the bacterial membrane but neither of the anthelmintic drugs exhibited demonstrable toxicity to sheep erythrocytes. Oxyclozanide was non-toxic to HepG2 human liver carcinoma cells within the range of its in vitro MICs but niclosamide displayed toxicity even at low concentrations. These data show that the salicylanilide anthelmintic drugs niclosamide and oxyclozanide are suitable candidates for mechanism of action studies and further clinical evaluation for treatment of staphylococcal infections.

  14. Application of X-ray microanalysis to the study of drug uptake in cell culture

    International Nuclear Information System (INIS)

    Reasor, M.J.; Lee, P.; Kirk, R.G.

    1990-01-01

    X-ray microanalysis has been used previously to study the accumulation of iodine in alveolar macrophages of rats treated with the iodinated drug, amiodarone. Due to metabolism of the drug in vivo, primarily to desethylamiodarone, it was not possible to identify the source of the iodine signal. In the present study we have utilized primary cell cultures of alveolar macrophages to study the intracellular accumulation of each of these drug species in vitro. Neither drug is metabolized by these cells in culture, permitting characterization of the accumulation of each independent of the other. Cells were incubated with equimolar concentrations of either amiodarone or desethylamiodarone for 42 hr, and X-ray microanalysis of freeze-dried cryosections of cells was used to quantify accumulation by monitoring the iodine signal associated with each drug. For both drug exposures, the highest iodine content was present in amorphous bodies and dense granules, consistent with the pattern following in vivo exposure. Higher levels of desethylamiodarone, compared to amiodarone, were measured in all compartments of the cells. The results of the in vitro investigation further demonstrate the utility of X-ray microanalysis in the study of the cellular response to amiodarone and desethylamiodarone

  15. Topical Drugs for Pain Relief

    Directory of Open Access Journals (Sweden)

    Anjali Srinivasan

    2015-03-01

    Full Text Available Topical therapy helps patients with oral and perioral pain problems such as ulcers, burning mouth syndrome, temporomandibular disorders, neuromas, neuropathies and neuralgias. Topical drugs used in the field of dentistry are topical anaesthetics, topical analgesics, topical antibiotics and topical corticosteroids. It provides symptomatic/curative effect. Topical drugs are easy to apply, avoids hepatic first pass metabolism and more sites specific. But it can only be used for medications that require low plasma concentrations to achieve a therapeutic effect.

  16. Drug Facts

    Medline Plus

    Full Text Available ... Phone Numbers and Websites Search Share Listen English Español Information about this page Click on the button ... sobre el abuso de drogas, y adicción. English Español About the National Institute on Drug Abuse (NIDA) | ...

  17. Drugs reviews

    African Journals Online (AJOL)

    Angel_D

    tests (LFTs) to monitor hepatotoxicity (liver [hepatic] damage) is uncommon in many resource-poor ... cholesterol ester storage disease. ... The problem with many patients is that they are taking several drugs often ... Urine, saliva and other body fluids may be coloured orange-red: this can be very alarming to patients.

  18. Drug resistance

    NARCIS (Netherlands)

    Gorter, J.A.; Potschka, H.; Noebels, J.L.; Avoli, M.; Rogawski, M.A.; Olsen, R.W.; Delgado-Escueta, A.V.

    2012-01-01

    Drug resistance remains to be one of the major challenges in epilepsy therapy. Identification of factors that contribute to therapeutic failure is crucial for future development of novel therapeutic strategies for difficult-to-treat epilepsies. Several clinical studies have shown that high seizure

  19. Capping Drugs

    Indian Academy of Sciences (India)

    preventing disease in human beings or in animals. In the process ... of requirement. In the process, they may cause toxic side effects. .... the liver to release the physiologically active drug. Similarly ... patients addicted to alcohol. However, it is a ...

  20. Drug Facts

    Medline Plus

    Full Text Available ... Prevention Phone Numbers and Websites Search Share Listen English Español Information about this page Click on the ... información sobre el abuso de drogas, y adicción. English Español About the National Institute on Drug Abuse ( ...

  1. Adverse drug reactions induced by cardiovascular drugs in outpatients

    Directory of Open Access Journals (Sweden)

    Gholami K

    2008-03-01

    Full Text Available Considering increased use of cardiovascular drugs and limitations in pre-marketing trials for drug safety evaluation, post marketing evaluation of adverse drug reactions (ADRs induced by this class of medicinal products seems necessary.Objectives: To determine the rate and seriousness of adverse reactions induced by cardiovascular drugs in outpatients. To compare sex and different age groups in developing ADRs with cardiovascular agents. To assess the relationship between frequencies of ADRs and the number of drugs used. Methods: This cross-sectional study was done in cardiovascular clinic at a teaching hospital. All patients during an eight months period were evaluated for cardiovascular drugs induced ADRs. Patient and reaction factors were analyzed in detected ADRs. Patients with or without ADRs were compared in sex and age by using chi-square test. Assessing the relationship between frequencies of ADRs and the number of drugs used was done by using Pearson analysis. Results: The total number of 518 patients was visited at the clinic. ADRs were detected in 105 (20.3% patients. The most frequent ADRs were occurred in the age group of 51-60. The highest rate of ADRs was recorded to be induced by Diltiazem (23.5% and the lowest rate with Atenolol (3%. Headache was the most frequent detected ADR (23%. Assessing the severity and preventability of ADRs revealed that 1.1% of ADRs were detected as severe and 1.9% as preventable reactions. Women significantly developed more ADRs in this study (chi square = 3.978, P<0.05. ADRs more frequently occurred with increasing age in this study (chi square = 15.871, P<0.05. With increasing the number of drugs used, the frequency of ADRs increased (Pearson=0.259, P<0.05. Conclusion: Monitoring ADRs in patients using cardiovascular drugs is a matter of importance since this class of medicines is usually used by elderly patients with critical conditions and underlying diseases.

  2. Drug abuse first aid

    Science.gov (United States)

    ... use of these drugs is a form of drug abuse. Medicines that are for treating a health problem ... about local resources. Alternative Names Overdose from drugs; Drug abuse first aid References Myck MB. Hallucinogens and drugs ...

  3. Bioresponsive matrices in drug delivery

    Directory of Open Access Journals (Sweden)

    Ye George JC

    2010-11-01

    Full Text Available Abstract For years, the field of drug delivery has focused on (1 controlling the release of a therapeutic and (2 targeting the therapeutic to a specific cell type. These research endeavors have concentrated mainly on the development of new degradable polymers and molecule-labeled drug delivery vehicles. Recent interest in biomaterials that respond to their environment have opened new methods to trigger the release of drugs and localize the therapeutic within a particular site. These novel biomaterials, usually termed "smart" or "intelligent", are able to deliver a therapeutic agent based on either environmental cues or a remote stimulus. Stimuli-responsive materials could potentially elicit a therapeutically effective dose without adverse side effects. Polymers responding to different stimuli, such as pH, light, temperature, ultrasound, magnetism, or biomolecules have been investigated as potential drug delivery vehicles. This review describes the most recent advances in "smart" drug delivery systems that respond to one or multiple stimuli.

  4. Detection and aggregation of the antitumoral drug parietin in ethanol/water mixture and on plasmonic metal nanoparticles studied by surface-enhanced optical spectroscopy: Effect of pH and ethanol concentration

    Science.gov (United States)

    Lopez-Tobar, Eduardo; Verebova, Valeria; Blascakova, Ludmila; Jancura, Daniel; Fabriciova, Gabriela; Sanchez-Cortes, Santiago

    2016-04-01

    In the present paper, we have investigated the effect of ethanol in aqueous media, the pH and the presence of Ag nanoparticles (NPs) on the aggregation processes of the antitumoral anthraquinone parietin in aqueous media and on the metal surface. UV-visible absorption, fluorescence and Raman spectra of parietin were used for such purpose. The present study provides information about the deprotonation and molecular aggregation processes occurring in parietin under different environments: ethanol/water mixture and when adsorbed onto Ag nanoparticles. The effect of ethanol on the optical properties of parietin in alcohol-water mixtures was also investigated at different ethanol concentrations with the time. For the case of the adsorption and organization of parietin molecules on the surface of Ag NPs, special attention was paid to the use of surface-enhanced optical techniques, SEF (surface-enhanced fluorescence) and SERS (surface-enhanced Raman scattering), for the characterization of the parietin aggregates and the ionization of the molecule on the surface. In particular, we have studied the variation of the SEF signal with the pH, which depends on the molecular organization of the molecule on the surface. Furthermore, a detailed analysis of the SERS spectra at different pH was accomplished and the main Raman bands of the protonated, mono-deprotonated and di-deprotonated parietin were identified. Finally, the second ionization pK of parietin on metal NPs was deduced from the SERS spectra.

  5. 21 CFR 169.176 - Concentrated vanilla extract.

    Science.gov (United States)

    2010-04-01

    ... content of ethyl alcohol is not less than 35 percent by volume. (b) The specified name of the food is... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Concentrated vanilla extract. 169.176 Section 169.176 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

  6. 21 CFR 146.145 - Orange juice from concentrate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Orange juice from concentrate. 146.145 Section 146... Juices and Beverages § 146.145 Orange juice from concentrate. (a) Orange juice from concentrate is the food prepared by mixing water with frozen concentrated orange juice as defined in § 146.146 or with...

  7. 21 CFR 146.150 - Canned concentrated orange juice.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Canned concentrated orange juice. 146.150 Section... Fruit Juices and Beverages § 146.150 Canned concentrated orange juice. (a) Canned concentrated orange... labeling of ingredients prescribed for frozen concentrated orange juice by § 146.146, except that it is not...

  8. Gentamicin concentration gradients in scala tympani perilymph following systemic applications.

    Science.gov (United States)

    Hahn, Hartmut; Salt, Alec N; Schumacher, Ulrike; Plontke, Stefan K

    2013-01-01

    It has been shown in prior studies that round window membrane (RWM) application of gentamicin produced a robust basal-apical concentration gradient in the perilymph of scala tympani (ST) with peak concentrations in the basal turn of ST. These gradients potentially contribute to the clinical efficacy and safety of intratympanic gentamicin applications for the treatment of Ménière's disease. The present study aimed to establish the distribution of gentamicin along ST perilymph after systemic applications. Gentamicin sulfate was applied intravenously in the amounts of 100, 300 and 600 mg/kg body weight (BW) over a period of 3 h or as a 300 mg/kg BW subcutaneous bolus injection. At 3 and 5 h after the start of the application perilymph of ST was aspirated from the cochlea apex of the right and left cochlea, respectively, and 10 sequential 1-µl perilymph samples from the apex of each cochlea were quantitatively analyzed using a fluorescence polarization immunoassay. In contrast to local RWM delivery, systemic application of gentamicin resulted in the highest perilymph levels in the apex of the cochlea with decreasing concentrations towards the basal regions of ST. The absolute gentamicin concentrations increased with the amount of drug applied and time before sampling. While it is likely that the basal-apical gradient measured after local drug applications to the round window niche is the result of the direct uptake of drugs into the perilymph of the ST, distribution by diffusion and a very low perilymph flow towards the cochlear apex, computer simulations suggested that the apical-basal gradient observed with these systemic applications can be explained by higher entry rates of gentamicin in the apex compared to the basal turns of the cochlea. It is also possible that gentamicin enters perilymph indirectly from the blood via the endolymph. In this case the faster kinetics in apical turns could be due to the smaller cross-sectional area of ST relative to endolymph in

  9. Influence of tiamulin concentration in feed on its bioavailability in piglets.

    Science.gov (United States)

    Riond, J L; Schreiber, F; Wanner, M

    1993-01-01

    Tiamulin pharmacokinetic parameters were determined in 8 2-month-old male improved Swiss Landrace piglets after intake of 2,000 mg/kg feed, 500 mg/kg feed, 12.5 mg/ml aqueous solution administered via a stomach tube and 180 mg/kg feed offered ad libitum. In all cases, the total tiamulin dose received was 10 mg/kg body weight (bw) per day. For the 2,000 mg/kg and 500 mg/kg treatments, animals were restrictively fed a commercial mix in amounts corresponding to 3-fold their maintenance requirement of digestible energy. The piglets first individually received the amount of medicated feed and immediately thereafter the rest of the daily ration. The highest tiamulin serum concentrations (Cmax), the largest area under the curve (AUC0-->infinity), the largest absorption rate constant (Ka), and the shortest time at which the maximum serum concentration occurred (tmax) were obtained after administration via stomach tube followed in the respective order by the 2,000 mg/kg, 500 mg/kg and 180 mg/kg treatments. Ad libitum feeding of the medicated mix at 180 mg/kg failed to provide tiamulin serum concentration above minimum inhibitory concentrations (MIC) of some representative microorganisms. In conclusion, tiamulin concentration in medicated feed strongly influences its rate and extent of absorption and consequently serum concentrations. Larger tiamulin concentration in feed enhances its bioavailability. The common practice adopted by national regulatory agencies for the registration of a new drug is to conduct pharmacokinetic studies after administration agencies for the registration of a new drug is to conduct pharmacokinetic studies after administration via a stomach tube. This practice should be reevaluated because this mode of administration does not correspond to that in routine use.

  10. Study on interaction of gastrointestinal agents in the presence of cytoprotective drugs. Part III. In vitro study on the adsorption of selected prokinetic drugs on sucralfate.

    Science.gov (United States)

    Grimling, Bozena; Pluta, Janusz

    2005-01-01

    Adsorbance of certain prokinetic drugs, regulating the motility of the digestive tract, on a cytoprotective drug--sucralfate was investigated. The evaluation of adsorbance capability was carried out by means of a statistical method in in vitro conditions, taking into account environmental pH, concentration of the investigated drugs as well as the form of sucralfate. Obtained results prove that the analyzed active agents are adsorbed on sucralfate at all the investigated pH ranges and the capability of sucralfate binding depends on its form and environmental pH. The highest binding capability was revealed by samples with pH = 3.6 in the presence of sucralfate in the form of suspension, while the lowest binding capability was observed at pH = 1.5 in the presence of sucralfate in the form of paste. The adsorbance capacity of sucralfate (k) at pH = 3.6 is the highest for cisaprid (k = 8.5) and it is significantly lower for metoclopramide (k = 1.5)

  11. Drug Safety: Managing Multiple Drugs

    Science.gov (United States)

    ... This series is produced by Consumers Union and Consumer Reports Best Buy Drugs , a public information project sup- ported by grants from the Engelberg Foundation and the National Library of Medicine of ... Consumer and Prescriber Education Grant Program which is funded ...

  12. Legal Drugs Are Good Drugs And Illegal Drugs Are Bad Drugs

    Directory of Open Access Journals (Sweden)

    Dina Indrati

    2011-07-01

    Full Text Available ABSTRACT : Labelling drugs are important issue nowadays in a modern society. Although it is generally believed that legal drugs are good drugs and illegal drugs are bad drugs, it is evident that some people do not aware about the side effects of drugs used. Therefore, a key contention of this philosophical essay is that explores harms minimisation policy, discuss whether legal drugs are good drugs and illegal drugs are bad drugs and explores relation of drugs misuse in a psychiatric nursing setting and dual diagnosis.Key words: Legal, good drugs, illegal, bad drugs.

  13. Impact of orphan drugs on Latvian budget.

    Science.gov (United States)

    Logviss, Konstantins; Krievins, Dainis; Purvina, Santa

    2016-05-11

    Number of orphan medicinal products on the market and number of rare disease patients, taking these usually expensive products, are increasing. As a result, budget impact of orphan drugs is growing. This factor, along with the cost-effectiveness of orphan drugs, is often considered in the reimbursement decisions, directly affecting accessibility of rare disease therapies. The current study aims to assess the budget impact of orphan drugs in Latvia. Our study covered a 5-year period, from 2010 to 2014. Impact of orphan drugs on Latvian budget was estimated from the National Health Service's perspective. It was calculated in absolute values and relative to total pharmaceutical market and total drug reimbursement budget. A literature review was performed for comparison with other European countries. Orphan drug annual expenditure ranged between EUR 2.065 and 3.065 million, with total 5-year expenditure EUR 12.467 million. It constituted, on average, 0.84 % of total pharmaceutical market and 2.14 % of total drug reimbursement budget, respectively. Average annual per patient expenditures varied widely, from EUR 1 534 to EUR 580 952. The most costly treatment was enzyme replacement therapy (Elaprase) for MPS II. Glivec had the highest share (34 %) of the total orphan drug expenditure. Oncological drugs represented more than a half of the total orphan drug expenditure, followed by drugs for metabolic and endocrine conditions and medicines for cardiopulmonary diseases. Three indications: Ph+ CML, MPS II, and PAH accounted for nearly 90 % of the total orphan drug expenditure. Budget impact of orphan drugs in Latvia is very small. It increased slightly over a period of five years, due to the slight increase in the number of patients and the number of orphan drugs reimbursed. Current Latvian drug reimbursement system is not sufficient for most orphan drugs.

  14. mtct regimen choice, drug resistance and the treatment of hiv

    African Journals Online (AJOL)

    risk of transmission is highest during labour and delivery, ... will have a major impact on controlling perinatally acquired HIV infection. ... could result in the development of drug resistance with potential .... dosing, pharmacokinetics and safety.

  15. Drug induced rhabdomyolysis

    Science.gov (United States)

    Hohenegger, Martin

    2012-01-01

    Rhabdomyolysis is a clinical condition of potential life threatening destruction of skeletal muscle caused by diverse mechanisms including drugs and toxins. Given the fact that structurally not related compounds cause an identical phenotype pinpoints to common targets or pathways, responsible for executing rhabdomyolysis. A drop in myoplasmic ATP paralleled with sustained elevations in cytosolic Ca2+ concentration represents a common signature of rhabdomyolysis. Interestingly, cardiac tissue is hardly affected or only secondary, as a consequence of imbalance in electrolytes or acid–base equilibrium. This dogma is now impaired by compounds, which show up with combined toxicity in heart and skeletal muscle. In this review, cases of rhabdomyolysis with novel recently approved drugs will be explored for new target mechanisms in the light of previously described pathomechanisms. PMID:22560920

  16. Contamination profiles, mass loadings, and sewage epidemiology of neuropsychiatric and illicit drugs in wastewater and river waters from a community in the Midwestern United States.

    Science.gov (United States)

    Skees, Allie J; Foppe, Katelyn S; Loganathan, Bommanna; Subedi, Bikram

    2018-08-01

    In this study, residues of the neuropsychiatric and illicit drugs including stimulants, opioids, hallucinogens, antischizophrenics, sedatives, and antidepressants were determined in influent and effluent samples from a small wastewater treatment plant, a receiving creek, and river waters in the Four Rivers region of the Midwestern United States. Nineteen neuropsychiatric drugs, eight illicit drugs, and three metabolites of illicit drugs were detected and quantitated in the water samples using HPLC-MS/MS. Residual concentrations of the drugs varied from below the detection limit to sub-μg/L levels. The source of residual cocaine and benzoylecgonine in wastewater is primarily from human consumption of cocaine rather than direct disposal. Wastewater based epidemiology is utilized to estimate the community usage of drugs based on the concentration of drug residues in wastewater, wastewater inflow, and the population served by the centralized wastewater treatment plant. The per-capita consumption rate of methamphetamine (1740 mg/d/1000 people) and amphetamine (970 mg/d/1000 people) found in this study were the highest reported per-capita consumption rates in the USA. Antidepressant venlafaxine found to have the highest environmental emission from the WWTP (333 ± 160 mg/d/1000 people) followed by citalopram (132 ± 60.2 mg/d/1000 people), methamphetamine (111 ± 43.6 mg/d/1000 people), and hydrocodone (108 ± 90.1 mg/d/1000 people). Bee Creek, an immediate receiving water body, is found to be a source of several neuropsychiatric and illicit drugs including methamphetamine, methadone, alprazolam, oxazepam, temazepam, carbamazepine, venlafaxine, citalopram, sertraline, oxycodone, and hydrocodone (p < 0.036) in the Clarks River. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Adverse drug reactions induced by cardiovascular drugs in outpatients.

    Science.gov (United States)

    Gholami, Kheirollah; Ziaie, Shadi; Shalviri, Gloria

    2008-01-01

    Considering increased use of cardiovascular drugs and limitations in pre-marketing trials for drug safety evaluation, post marketing evaluation of adverse drug reactions (ADRs) induced by this class of medicinal products seems necessary. To determine the rate and seriousness of adverse reactions induced by cardiovascular drugs in outpatients. To compare sex and different age groups in developing ADRs with cardiovascular agents. To assess the relationship between frequencies of ADRs and the number of drugs used. This cross-sectional study was done in cardiovascular clinic at a teaching hospital. All patients during an eight months period were evaluated for cardiovascular drugs induced ADRs. Patient and reaction factors were analyzed in detected ADRs. Patients with or without ADRs were compared in sex and age by using chi-square test. Assessing the relationship between frequencies of ADRs and the number of drugs used was done by using Pearson analysis. The total number of 518 patients was visited at the clinic. ADRs were detected in 105 (20.3%) patients. The most frequent ADRs were occurred in the age group of 51-60. The highest rate of ADRs was recorded to be induced by Diltiazem (23.5%) and the lowest rate with Atenolol (3%). Headache was the most frequent detected ADR (23%). Assessing the severity and preventability of ADRs revealed that 1.1% of ADRs were detected as severe and 1.9% as preventable reactions. Women significantly developed more ADRs in this study (chi square = 3.978, PPearson=0.259, P<0.05). Monitoring ADRs in patients using cardiovascular drugs is a matter of importance since this class of medicines is usually used by elderly patients with critical conditions and underlying diseases.

  18. Electrodynamics at the highest energies

    International Nuclear Information System (INIS)

    Klein, Spencer R.

    2002-01-01

    At very high energies, the bremsstrahlung and pair production cross sections exhibit complex behavior due to the material in which the interactions occur. The cross sections in dense media can be dramatically different than for isolated atoms. This writeup discusses these in-medium effects, emphasizing how the cross section has different energy and target density dependencies in different regimes. Data from SLAC experiment E-146 will be presented to confirm the energy and density scaling. Finally, QCD analogs of the electrodynamics effects will be discussed

  19. Vermont Highest Priority Connectivity Blocks

    Data.gov (United States)

    Vermont Center for Geographic Information — Act 174 requires plans to identify potential areas for the development and siting of renewable energy resources and areas that are unsuitable for siting those...

  20. Fertility drugs and ovarian cancer.

    Science.gov (United States)

    Ali, Aus Tariq

    2017-06-20

    The aetiology of ovarian cancer is multifactorial with both endogenous and exogenous risk factors playing an important role. The exact pathogenesis of ovarian cancer is still not well understood, despite the number of hypotheses published. Due to an increase in the number of women using fertility drugs, much attention has been focused on the long-term health effects of such drugs. Although fertility drugs facilitate the ovulation process, it is however associated with a significant increase in hormone concentrations, placing exposed women at increased risk of gynaecological cancer. Many clinical and epidemiological studies have examined the association between fertility drugs and ovarian cancer risk. Results from these studies have been contradictory, as some studies have reported an increased risk of ovarian cancer while others reported no increased risk. Nevertheless, recent studies have shown that women who used fertility drugs and did not conceive had a higher risk of developing ovarian cancer, compared to women who used fertility drugs and conceived and delivered successfully. This review discusses the effect of fertility drugs on the risk of developing ovarian cancer, providing details on four possible scenarios associated with fertility treatment. In addition, the limitations of previous studies and their impact on our understanding of the association between fertility drugs and ovarian cancer also have been highlighted. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. [Interactions of cytostatic agents with other drugs].

    Science.gov (United States)

    Sauter, C

    1991-08-31

    With the degree of polypharmacy currently practiced in the field of oncology, there are undoubtedly many drug interactions. In the present study the influence of "non-cytotoxic" drugs on anticancer drugs is discussed, but not the reverse. Not only is the augmentation (reversal of multidrug resistance) or the reduction of antitumor properties of cytotoxic drugs observed, but also cytostatic activities of "non-cytotoxic" drugs themselves. Examples are calmodulin inhibitors such as phenothiazines and tricyclic antidepressants. Interactions may also increase side effects of cytostatic drugs or even neutralize the antitumoral activity. To ensure that interactions are not overlooked, all medicaments being administered should be listed. It is, however, not feasible yet to determine serum concentrations of all the drugs given to the patient. The antitumor activity of supportive care could be evaluated in randomized studies (e.g. cytostatic drugs +/- antidepressants).

  2. 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.

  3. [Influence of quaternary ammonium salt on liberation of drug with antiseptic effect].

    Science.gov (United States)

    Vitková, Zuzana; Herdová, Petra; Oremusová, Jarmila; Cižmárik, Jozef; Tóthová, Katarína

    2013-12-01

    The paper evaluates the influence of three surfactants (carbetopendecinium halogenides) on the liberation of the drug chlorhexidine dihydrochloride (CHX) in 0.1% (w/w) from the dosage form-gel and also the flow properties of gels. The following tensides were evaluated: carbetopendecinium bromide (SB), carbetopendecinium chloride (SC), and carbetopendecinium iodide (SI). The tenside concentration was set under the critical micelle concentration. The biopolymer - chitosan (CHIT) in 2.5% (w/w) concentration was used as a gel creating substance. Based on the flow properties of the studied gels, it was found that the employed tensides exhibited no influence on the character of the system. The gels exhibited the character of plastic systems with time-independent flow. The drug liberation was evaluated at the temperatures of 20, 30 and 40 °C. Between the types of the tensides, the statistically significant differences (P < 0.05) were found as to the amount of the liberated CHX, which was reflected by the increased amount of the liberated drug. Based on the obtained results, it can be concluded that the most suitable was the SI tenside. From the gel with this tenside the greatest amount of CHX was liberated, which had the highest value of the liberation rate constant.

  4. Drug screen in patient cells suggests quinacrine to be repositioned for treatment of acute myeloid leukemia

    International Nuclear Information System (INIS)

    Eriksson, A; Österroos, A; Hassan, S; Gullbo, J; Rickardson, L; Jarvius, M; Nygren, P; Fryknäs, M; Höglund, M; Larsson, R

    2015-01-01

    To find drugs suitable for repositioning for use against leukemia, samples from patients with chronic lymphocytic, acute myeloid and lymphocytic leukemias as well as peripheral blood mononuclear cells (PBMC) were tested in response to 1266 compounds from the LOPAC 1280 library (Sigma). Twenty-five compounds were defined as hits with activity in all leukemia subgroups (<50% cell survival compared with control) at 10 μM drug concentration. Only one of these compounds, quinacrine, showed low activity in normal PBMCs and was therefore selected for further preclinical evaluation. Mining the NCI-60 and the NextBio databases demonstrated leukemia sensitivity and the ability of quinacrine to reverse myeloid leukemia gene expression. Mechanistic exploration was performed using the NextBio bioinformatic software using gene expression analysis of drug exposed acute myeloid leukemia cultures (HL-60) in the database. Analysis of gene enrichment and drug correlations revealed strong connections to ribosomal biogenesis nucleoli and translation initiation. The highest drug–drug correlation was to ellipticine, a known RNA polymerase I inhibitor. These results were validated by additional gene expression analysis performed in-house. Quinacrine induced early inhibition of protein synthesis supporting these predictions. The results suggest that quinacrine have repositioning potential for treatment of acute myeloid leukemia by targeting of ribosomal biogenesis

  5. “Time for dabs”: Analyzing Twitter data on marijuana concentrates across the U.S.

    Science.gov (United States)

    Daniulaityte, Raminta; Nahhas, Ramzi W.; Wijeratne, Sanjaya; Carlson, Robert G.; Lamy, Francois R.; Martins, Silvia S.; Boyer, Edward W.; Smith, G. Alan; Sheth, Amit

    2015-01-01

    Aims Media reports suggest increasing popularity of marijuana concentrates (“dabs”; “earwax”; “budder”; “shatter; “butane hash oil”) that are typically vaporized and inhaled via a bong, vaporizer or electronic cigarette. However, data on the epidemiology of marijuana concentrate use remain limited. This study aims to explore Twitter data on marijuana concentrate use in the U.S. and identify differences across regions of the country with varying cannabis legalization policies. Methods Tweets were collected between October 20 and December 20, 2014, using Twitter's streaming API. Twitter data filtering framework was available through the eDrugTrends platform. Raw and adjusted percentages of dabs-related tweets per state were calculated. A permutation test was used to examine differences in the adjusted percentages of dabs-related tweets among U.S. states with different cannabis legalization policies. Results eDrugTrends collected a total of 125,255 tweets. Almost 22% (n=27,018) of these tweets contained identifiable state-level geolocation information. Dabs-related tweet volume for each state was adjusted using a general sample of tweets to account for different levels of overall tweeting activity for each state. Adjusted percentages of dabs-related tweets were highest in states that allowed recreational and/or medicinal cannabis use and lowest in states that have not passed medical cannabis use laws. The differences were statistically significant. Conclusions Twitter data suggest greater popularity of dabs in the states that legalized recreational and/or medical use of cannabis. The study provides new information on the epidemiology of marijuana concentrate use and contributes to the emerging field of social media analysis for drug abuse research. PMID:26338481

  6. "Time for dabs": Analyzing Twitter data on marijuana concentrates across the U.S.

    Science.gov (United States)

    Daniulaityte, Raminta; Nahhas, Ramzi W; Wijeratne, Sanjaya; Carlson, Robert G; Lamy, Francois R; Martins, Silvia S; Boyer, Edward W; Smith, G Alan; Sheth, Amit

    2015-10-01

    Media reports suggest increasing popularity of marijuana concentrates ("dabs"; "earwax"; "budder"; "shatter; "butane hash oil") that are typically vaporized and inhaled via a bong, vaporizer or electronic cigarette. However, data on the epidemiology of marijuana concentrate use remain limited. This study aims to explore Twitter data on marijuana concentrate use in the U.S. and identify differences across regions of the country with varying cannabis legalization policies. Tweets were collected between October 20 and December 20, 2014, using Twitter's streaming API. Twitter data filtering framework was available through the eDrugTrends platform. Raw and adjusted percentages of dabs-related tweets per state were calculated. A permutation test was used to examine differences in the adjusted percentages of dabs-related tweets among U.S. states with different cannabis legalization policies. eDrugTrends collected a total of 125,255 tweets. Almost 22% (n=27,018) of these tweets contained identifiable state-level geolocation information. Dabs-related tweet volume for each state was adjusted using a general sample of tweets to account for different levels of overall tweeting activity for each state. Adjusted percentages of dabs-related tweets were highest in states that allowed recreational and/or medicinal cannabis use and lowest in states that have not passed medical cannabis use laws. The differences were statistically significant. Twitter data suggest greater popularity of dabs in the states that legalized recreational and/or medical use of cannabis. The study provides new information on the epidemiology of marijuana concentrate use and contributes to the emerging field of social media analysis for drug abuse research. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Optimization of Drug Delivery by Drug-Eluting Stents.

    Directory of Open Access Journals (Sweden)

    Franz Bozsak

    Full Text Available Drug-eluting stents (DES, which release anti-proliferative drugs into the arterial wall in a controlled manner, have drastically reduced the rate of in-stent restenosis and revolutionized the treatment of atherosclerosis. However, late stent thrombosis remains a safety concern in DES, mainly due to delayed healing of the endothelial wound inflicted during DES implantation. We present a framework to optimize DES design such that restenosis is inhibited without affecting the endothelial healing process. To this end, we have developed a computational model of fluid flow and drug transport in stented arteries and have used this model to establish a metric for quantifying DES performance. The model takes into account the multi-layered structure of the arterial wall and incorporates a reversible binding model to describe drug interaction with the cells of the arterial wall. The model is coupled to a novel optimization algorithm that allows identification of optimal DES designs. We show that optimizing the period of drug release from DES and the initial drug concentration within the coating has a drastic effect on DES performance. Paclitaxel-eluting stents perform optimally by releasing their drug either very rapidly (within a few hours or very slowly (over periods of several months up to one year at concentrations considerably lower than current DES. In contrast, sirolimus-eluting stents perform optimally only when drug release is slow. The results offer explanations for recent trends in the development of DES and demonstrate the potential for large improvements in DES design relative to the current state of commercial devices.

  8. Acyclic cucurbit[n]uril-type molecular containers: influence of aromatic walls on their function as solubilizing excipients for insoluble drugs.

    Science.gov (United States)

    Zhang, Ben; Isaacs, Lyle

    2014-11-26

    We studied the influence of the aromatic sidewalls on the ability of acyclic CB[n]-type molecular containers (1a-1e) to act as solubilizing agents for 19 insoluble drugs including the developmental anticancer agent PBS-1086. All five containers exhibit good water solubility and weak self-association (Ks ≤ 624 M(-1)). We constructed phase solubility diagrams to extract Krel and Ka values for the container·drug complexes. The acyclic CB[n]-type containers generally display significantly higher Ka values than HP-β-CD toward drugs. Containers 1a-1e bind the steroidal ring system and aromatic moieties of insoluble drugs. Compound 1b displays highest affinity toward most of the drugs studied. Containers 1a and 1b are broadly applicable and can be used to formulate a wider variety of insoluble drugs than was previously possible with cyclodextrin technology. For drugs that are solubilized by both HP-β-CD and 1a-1e, lower concentrations of 1a-1e are required to achieve identical [drug].

  9. Dissolved Platinum Concentrations in Coastal Seawater: Boso to Sanriku Areas, Japan.

    Science.gov (United States)

    Mashio, Asami Suzuki; Obata, Hajime; Gamo, Toshitaka

    2017-08-01

    Platinum, one of the rarest elements in the earth's crust, is now widely used in a range of products, such as catalytic converters in automobiles and anticancer drugs. Increasing use and dispersal of platinum has the potential to affect aquatic environments. Platinum concentrations in open ocean seawater have been found to be very low (approximately 0.2 pmol/L); however, Pt distributions and biogeochemical cycles in coastal areas are unknown. In this study, we investigated Pt concentrations in coastal waters between the Boso and Sanriku areas, Japan, after the 2011 tsunami. We determined sub-picomolar levels of dissolved Pt using isotope-dilution Inductively coupled plasma mass spectrometry after column preconcentration with an anion exchange resin. Dissolved Pt concentrations were found to be in the range 0.20-1.5 pmol/L, with the highest concentration in bottom water of the Boso coastal area, and at stations close to Tokyo Bay. Assuming thermodynamical equilibrium, Pt was determined to be present in the form PtCl 5 (OH) 2- , even in low-oxygen coastal waters. Vertical profiles indicated Pt levels increased toward seafloors near coastal stations and were similar to those of the open ocean at trench stations. High concentrations of dissolved Pt are thought to be derived from coastal sediments.

  10. Hyaluronan-decorated liposomes as drug delivery systems for cutaneous administration.

    Science.gov (United States)

    Franzé, Silvia; Marengo, Alessandro; Stella, Barbara; Minghetti, Paola; Arpicco, Silvia; Cilurzo, Francesco

    2018-01-15

    The work aimed to evaluate the feasibility to design hyaluronic acid (HA) decorated flexible liposomes to enhance the skin penetration of nifedipine. Egg phosphatidylcholine (e-PC) based transfersomes (Tween 80) and transethosomes (ethanol) were prepared. HA was reacted with 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (HA-DPPE) and two molar ratios (0.5 and 3%) of conjugate with respect to e-PC were tested. The presence of HA significantly increased the packing order of the bilayer (as verified by differential scanning calorimetry), reducing both the encapsulation efficiency and the flexibility of the decorated liposomes in a dose-dependent manner. In fact, at the highest HA content the constant of deformability (K, N/mm) increased and the carriers remained on the skin surface after topical application. The stiffening effect of HA was counterbalanced by the addition of ethanol as fluidizing agent that allowed to maintain the highest HA concentration, meanwhile reducing the K value of the vesicles. HA-transethosomes allowed a suitable nifedipine permeation (J ∼ 30 ng/cm 2 /h) and significantly improved the drug penetration, favouring the formation of a drug depot in the epidermis. These data suggest the potentialities of HA-transethosomes as drug delivery systems intended for the treatment of cutaneous pathologies and underline the importance of studying the effect of surface functionalization on carrier deformability to rationalize the design of such systems. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Drugs Approved for Neuroblastoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for neuroblastoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  12. Drugs Approved for Leukemia

    Science.gov (United States)

    This page lists cancer drugs approved by the FDA for use in leukemia. The drug names link to NCI's Cancer Drug Information summaries. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  13. Drugs Approved for Retinoblastoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for retinoblastoma. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  14. National Drug Code Directory

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Drug Listing Act of 1972 requires registered drug establishments to provide the Food and Drug Administration (FDA) with a current list of all drugs manufactured,...

  15. Other Drugs of Abuse

    Science.gov (United States)

    ... People Abuse » Other Drugs of Abuse Other Drugs of Abuse Listen There are many other drugs of abuse, ... and Rehab Resources About the National Institute on Drug Abuse (NIDA) | About This Website Tools and Resources | Contact ...

  16. Urine drug screen

    Science.gov (United States)

    Drug screen - urine ... detect the presence of illegal and some prescription drugs in your urine. Their presence may indicate that you recently used these drugs. Some drugs may remain in your system for ...

  17. Polypharmacology of Approved Anticancer Drugs.

    Science.gov (United States)

    Amelio, Ivano; Lisitsa, Andrey; Knight, Richard A; Melino, Gerry; Antonov, Alexey V

    2017-01-01

    The major drug discovery efforts in oncology have been concentrated on the development of selective molecules that are supposed to act specifically on one anticancer mechanism by modulating a single or several closely related drug targets. However, a bird's eye view on data from multiple available bioassays implies that most approved anticancer agents do, in fact, target many more proteins with different functions. Here we will review and systematize currently available information on the targets of several anticancer drugs along with revision of their potential mechanisms of action. Polypharmacology of the current antineoplastic agents suggests that drug clinical efficacy in oncology can be achieved only via modulation of multiple cellular mechanisms. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Development and Evaluation of Chronotherapeutic Drug Delivery ...

    African Journals Online (AJOL)

    Conclusion: The developed system is capable of releasing the drug after a 4-h lag period. However ... concentration would be at its maximum level, ... spheronizer (Caleva MBS, UK)operating at .... capsules show that the color intensity of the.

  19. Understanding drugs and behaviour

    National Research Council Canada - National Science Library

    Parrott, Andrew

    2004-01-01

    ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix xi Part I Drugs and Their Actions . . . . . . . . . . . . . . . . . . . . . . 1 Psychoactive drugs: introduction and overview . . . . . . . . 2 The brain...

  20. Solid lipid nanoparticles as anti-inflammatory drug delivery system in a human inflammatory bowel disease whole-blood model.

    Science.gov (United States)

    Serpe, Loredana; Canaparo, Roberto; Daperno, Marco; Sostegni, Raffaello; Martinasso, Germana; Muntoni, Elisabetta; Ippolito, Laura; Vivenza, Nicoletta; Pera, Angelo; Eandi, Mario; Gasco, Maria Rosa; Zara, Gian Paolo

    2010-03-18

    Standard treatment for inflammatory bowel diseases (IBD) necessitates frequent intake of anti-inflammatory and/or immunosuppressive drugs, leading to significant adverse events. To evaluate the role solid lipid nanoparticles (SLN) play as drug delivery system in enhancing anti-inflammatory activity for drugs such as dexamethasone and butyrate in a human inflammatory bowel diseases whole-blood model. ELISA assay and the peripheral blood mononuclear cell (PBMC) cytokine mRNA expression levels were evaluated by quantitative SYBR Green real-time RT-PCR to determine the IL-1beta, TNF-alpha, IFN-gamma and IL-10 secretion in inflammatory bowel diseases patients' PBMC culture supernatants. There was a significant decrease in IL-1beta (p<0.01) and TNF-alpha (p<0.001) secretion, whilst IL-10 (p<0.05) secretion significantly increased after cholesteryl butyrate administration, compared to that of butyrate alone at the highest concentration tested (100 microM), at 24h exposure. There was a significant decrease in IL-1beta (p<0.01), TNF-alpha (p<0.001) and IL-10 (p<0.001) secretion after dexamethasone loaded SLN administration, compared to dexamethasone alone at the highest concentration tested (250 nM) at 24h exposure. No IFN-gamma was detected under any conditions and no cytotoxic effects observed even at the highest concentration tested. The incorporation of butyrate and dexamethasone into SLN has a significant positive anti-inflammatory effect in the human inflammatory bowel disease whole-blood model. Copyright 2010 Elsevier B.V. All rights reserved.

  1. Metals in the Scheldt estuary: From environmental concentrations to bioaccumulation.

    Science.gov (United States)

    Van Ael, Evy; Blust, Ronny; Bervoets, Lieven

    2017-09-01

    To investigate the relationship between metal concentrations in abiotic compartments and in aquatic species, sediment, suspended matter and several aquatic species (Polychaeta, Oligochaeta, four crustacean species, three mollusc species and eight fish species) were collected during three seasons at six locations along the Scheldt estuary (the Netherlands-Belgium) and analysed on their metal content (Ag, Cd, Co, Cr, Cu, Ni, Pb, Zn and the metalloid As). Sediment and biota tissue concentrations were significantly influenced by sampling location, but not by season. Measurements of Acid Volatile Sulphides (AVS) concentrations in relation to Simultaneously Extracted Metals (SEM) in the sediment suggested that not all metals in the sediment will be bound to sulphides and some metals might be bioavailable. For all metals but zinc, highest concentrations were measured in invertebrate species; Ag and Ni in periwinkle, Cr, Co and Pb in Oligochaete worms and As, Cd and Cu in crabs and shrimp. Highest concentrations of Zn were measured in the kidney of European smelt. In fish, for most of the metals, the concentrations were highest in liver or kidney and lowest in muscle. For Zn however, highest concentrations were measured in the kidney of European smelt. For less than half of the metals significant correlations between sediment metal concentrations and bioaccumulated concentrations were found (liver/hepatopancreas or whole organism). To calculate the possible human health risk by consumption, average and maximum metal concentrations in the muscle tissues were compared to the minimum risk levels (MRLs). Concentrations of As led to the highest risk potential for all consumable species. Cadmium and Cu posed only a risk when consuming the highest contaminated shrimp and shore crabs. Consuming blue mussel could result in a risk for the metals As, Cd and Cr. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. The concentrations of uranium in marine organisms

    Energy Technology Data Exchange (ETDEWEB)

    Matsuba, Mitsue; Ishii, Toshiaki; Nakahara, Motokazu; Nakamura, Ryoichi; Watabe, Teruhisa; Hirano, Shigeki [National Inst. of Radiological Sciences, Hitachinaka, Ibaraki (Japan). Laboratory for Radioecology

    2000-07-01

    Determination of uranium in sixty-one species of marine organisms was carried out by inductively coupled plasma mass spectrometry to obtain concentration factors and to estimate the internal radiation dose. The concentrations of uranium in soft tissues of marine animals were ranged from 0.077 to 5040 ng/g wet wt. Especially, the branchial heart of cephalopod molluscs showed the specific accumulation of uranium. The concentration factor of the branchial heart of Octopus vulgaris, which indicated the highest value, was calculated to be about 1.6 x 10{sup 3}, comparing with that (3.1 ng/ml) in coastal seawaters of Japan. The concentrations of uranium in hard tissues of marine invertebrates such as clam and sea urchin were similar to those in soft tissues. In contrast, hard tissues like bone, scale, fin, etc. of fishes showed much higher concentrations of uranium than soft tissues like muscle. The concentrations of uranium of twenty-two species of algae were ranged from 2 to 310 ng/g wet wt. Particularly, the brown alga Undaria pinnatifida showed the highest value of the uranium content in the algae and its concentration factor was calculated to be 10{sup 2}. (author)

  3. The concentrations of uranium in marine organisms

    International Nuclear Information System (INIS)

    Matsuba, Mitsue; Ishii, Toshiaki; Nakahara, Motokazu; Nakamura, Ryoichi; Watabe, Teruhisa; Hirano, Shigeki

    2000-01-01

    Determination of uranium in sixty-one species of marine organisms was carried out by inductively coupled plasma mass spectrometry to obtain concentration factors and to estimate the internal radiation dose. The concentrations of uranium in soft tissues of marine animals were ranged from 0.077 to 5040 ng/g wet wt. Especially, the branchial heart of cephalopod molluscs showed the specific accumulation of uranium. The concentration factor of the branchial heart of Octopus vulgaris, which indicated the highest value, was calculated to be about 1.6 x 10 3 , comparing with that (3.1 ng/ml) in coastal seawaters of Japan. The concentrations of uranium in hard tissues of marine invertebrates such as clam and sea urchin were similar to those in soft tissues. In contrast, hard tissues like bone, scale, fin, etc. of fishes showed much higher concentrations of uranium than soft tissues like muscle. The concentrations of uranium of twenty-two species of algae were ranged from 2 to 310 ng/g wet wt. Particularly, the brown alga Undaria pinnatifida showed the highest value of the uranium content in the algae and its concentration factor was calculated to be 10 2 . (author)

  4. On the possibility of highest energy cosmic rays bursts and their correlation with gamma rays bursts e.g. March 5th, 1979 event

    International Nuclear Information System (INIS)

    Drukier, K.

    1982-01-01

    The avalanche production of magnetic monopoles is possible in neutron stars. Big part of the magnetic field energy can be used to accelerate a pulse of 10 30 monopoles to the energy E > approximately 10 17 eV. Thus the neutron stars may be ''point'' sources of bursts of highest energy Cosmic Rays. The emission of brehmsstrahlung photons by these highly relativistic monopoles would be seen as X and gamma bursts. This ''exotic'' model for March 5th, 1979 event, predicts that it has been followed by burst of highest energy Cosmic Rays coming from the direction of LMC supernovae remanent N49

  5. Therapeutic drug monitoring in pregnancy.

    Science.gov (United States)

    Matsui, Doreen M

    2012-10-01

    Therapeutic drug monitoring (TDM) is commonly recommended to optimize drug dosing regimens of various medications. It has been proposed to guide therapy in pregnant women, in whom physiological changes may lead to altered pharmacokinetics resulting in difficulty in predicting the appropriate drug dosage. Ideally, TDM may play a role in enhancing the effectiveness of treatment while minimizing toxicity of both the mother and fetus. Monitoring of drug levels may also be helpful in assessing adherence to prescribed therapy in selected cases. Limitations exist as therapeutic ranges have only been defined for a limited number of drugs and are based on data obtained in nonpregnant patients. TDM has been suggested for anticonvulsants, antidepressants, and antiretroviral drugs, based on pharmacokinetic studies that have shown reduced drug concentrations. However, there is only relatively limited (and sometimes inconsistent) information regarding the clinical impact of these pharmacokinetic changes during pregnancy and the effect of subsequent dose adjustments. Further studies are required to determine whether implementation of TDM during pregnancy improves outcome and is associated with any benefit beyond that achieved by clinical judgment alone. The cost effectiveness of TDM programs during pregnancy also remains to be examined.

  6. Prescription Drug Abuse

    Science.gov (United States)

    ... drug abuse. And it's illegal, just like taking street drugs. Why Do People Abuse Prescription Drugs? Some people abuse prescription drugs ... common risk of prescription drug abuse is addiction . People who abuse ... as if they were taking street drugs. That's one reason most doctors won't ...

  7. Drug abuse

    International Nuclear Information System (INIS)

    Simon, T.R.; Seastrunk, J.W.; Malone, G.; Knesevich, M.A.; Hickey, D.C.

    1991-01-01

    This paper reports that this study used SPECT to examine patients who have abused drugs to determine whether SPECT could identify abnormalities and whether these findings have clinical importance. Fifteen patients with a history of substance abuse (eight with cocaine, six with amphetamine, and one with organic solvent) underwent SPECT performed with a triple-headed camera and Tc-99m HMPAO both early for blood flow and later for functional information. These images were then processed into a 3D videotaped display used in group therapy. All 15 patients had multiple areas of decreased tracer uptake peppered throughout the cortex but mainly affecting the parietal lobes, expect for the organic solvent abuser who had a large parietal defect. The videotapes were subjectively described by a therapist as an exceptional tool that countered patient denial of physical damage from substance abuse. Statistical studies of recidivism between groups is under way

  8. Prevalence of alcohol and drugs among motorcycle riders killed in road crashes in Norway during 2001-2010.

    Science.gov (United States)

    Christophersen, Asbjørg S; Gjerde, Hallvard

    2015-07-01

    The aim of the study was to examine the prevalence of alcohol and drugs in blood samples from motorcycle riders who died in road crashes in Norway from 2001 to 2010. An additional aim was to compare the prevalence of alcohol and drugs in blood samples from fatally injured motorcycle riders and car drivers who died during the same time period. Blood samples from motorcycle riders who died within 24h after the accident (n=207, 63% of all killed riders), were analysed for alcohol, psychoactive drugs (medicinal and illicit drugs). The cut-off concentrations for alcohol and drugs findings in blood samples (i.e., the drug concentrations above which a finding was regarded as positive) were set according to the legislative limits under the Norwegian Road Traffic Act. Results were assessed in relation to age, sex, time of the day and week, and single versus multiple-vehicle accidents. Alcohol or drugs were found in 27.1 percent of all investigated riders. For riders killed in single or multiple-vehicle accidents, alcohol or drugs were found in 44.6 and 15.3 percent, respectively. Alcohol was the most frequently found substance for all age groups and most prevalent in samples from riders below 25 years who died in single-vehicle accidents (45.8 percent). Drugs were most often found among riders between 25 and 34 years (19.6 percent in total and 25.9% for those killed in single-vehicle crashes). The prevalence of alcohol or drugs was highest among riders killed in single-vehicle accidents during weekend days and nights (60.9 and 65.2 percent). Alcohol and drugs were less often found in samples from killed motorcycles riders than in samples from car and van drivers (40.2 percent). For single-vehicle accidents, the total prevalence of alcohol or drugs among killed motorcycles riders and car drivers was 44.6 percent and 63.8 percent, respectively. The same pattern of alcohol and drugs was found among the two groups, except that the prevalence among motorcycle riders was lower

  9. Registration for public drug benefits across areas of differing ethnic composition in British Columbia, Canada

    Directory of Open Access Journals (Sweden)

    Wong Sabrina T

    2010-06-01

    Full Text Available Abstract Background In 2003, the government of British Columbia, Canada introduced a universal drug benefit plan to cover drug costs that are high relative to household income. Residents were required to register in order to be eligible for the income-based benefits. Given past research suggesting that registration processes may pose an access barrier to certain subpopulations, we aimed to determine whether registration rates varied across small geographic areas that differed in ethnic composition. Methods Using linked population-based administrative databases and census data, we conducted multivariate logistic regression analyses to determine whether the probability of registration for the public drug plan varied across areas of differing ethnic composition, controlling for household-level predisposing, enabling and needs factors. Results The adjusted odds of registration did not differ across regions characterized by high concentrations (greater than 30% of residents identifying as North American, British, French or other European. Households located in areas with concentrations of residents identifying as an Asian ethnicity had the highest odds of program registration: Chinese (OR = 1.21, CI: 1.19-1.23 and South Asian (OR = 1.19, CI: 1.16-1.22. Despite this positive finding, households residing in areas with relatively high concentrations of recent immigrants had slightly lower adjusted odds of registering for the program (OR = 0.97, CI: 0.95-0.98. Conclusions This study identified ethnic variation in registration for a new public drug benefit program in British Columbia. However, unlike previous studies, the variation observed did not indicate that areas with high concentrations of certain ethnicities experienced disadvantages. Potential explanations are discussed.

  10. Registration for public drug benefits across areas of differing ethnic composition in British Columbia, Canada.

    Science.gov (United States)

    Leong, Vivian W; Morgan, Steve; Wong, Sabrina T; Hanley, Gillian E; Black, Charlyn

    2010-06-17

    In 2003, the government of British Columbia, Canada introduced a universal drug benefit plan to cover drug costs that are high relative to household income. Residents were required to register in order to be eligible for the income-based benefits. Given past research suggesting that registration processes may pose an access barrier to certain subpopulations, we aimed to determine whether registration rates varied across small geographic areas that differed in ethnic composition. Using linked population-based administrative databases and census data, we conducted multivariate logistic regression analyses to determine whether the probability of registration for the public drug plan varied across areas of differing ethnic composition, controlling for household-level predisposing, enabling and needs factors. The adjusted odds of registration did not differ across regions characterized by high concentrations (greater than 30%) of residents identifying as North American, British, French or other European. Households located in areas with concentrations of residents identifying as an Asian ethnicity had the highest odds of program registration: Chinese (OR = 1.21, CI: 1.19-1.23) and South Asian (OR = 1.19, CI: 1.16-1.22). Despite this positive finding, households residing in areas with relatively high concentrations of recent immigrants had slightly lower adjusted odds of registering for the program (OR = 0.97, CI: 0.95-0.98). This study identified ethnic variation in registration for a new public drug benefit program in British Columbia. However, unlike previous studies, the variation observed did not indicate that areas with high concentrations of certain ethnicities experienced disadvantages. Potential explanations are discussed.

  11. Development and validation of a general approach to predict and quantify the synergism of anti-cancer drugs using experimental design and artificial neural networks.

    Science.gov (United States)

    Pivetta, Tiziana; Isaia, Francesco; Trudu, Federica; Pani, Alessandra; Manca, Matteo; Perra, Daniela; Amato, Filippo; Havel, Josef

    2013-10-15

    The combination of two or more drugs using multidrug mixtures is a trend in the treatment of cancer. The goal is to search for a synergistic effect and thereby reduce the required dose and inhibit the development of resistance. An advanced model-free approach for data exploration and analysis, based on artificial neural networks (ANN) and experimental design is proposed to predict and quantify the synergism of drugs. The proposed method non-linearly correlates the concentrations of drugs with the cytotoxicity of the mixture, providing the possibility of choosing the optimal drug combination that gives the maximum synergism. The use of ANN allows for the prediction of the cytotoxicity of each combination of drugs in the chosen concentration interval. The method was validated by preparing and experimentally testing the combinations with the predicted highest synergistic effect. In all cases, the data predicted by the network were experimentally confirmed. The method was applied to several binary mixtures of cisplatin and [Cu(1,10-orthophenanthroline)2(H2O)](ClO4)2, Cu(1,10-orthophenanthroline)(H2O)2(ClO4)2 or [Cu(1,10-orthophenanthroline)2(imidazolidine-2-thione)](ClO4)2. The cytotoxicity of the two drugs, alone and in combination, was determined against human acute T-lymphoblastic leukemia cells (CCRF-CEM). For all systems, a synergistic effect was found for selected combinations. © 2013 Elsevier B.V. All rights reserved.

  12. Education Pays Off! On Transition to Work for 25 Year Olds in Norway with Upper Secondary Education or Lower as Their Highest Educational Level

    Science.gov (United States)

    Markussen, Eifred

    2017-01-01

    In this article we examine the relationship between educational level and position in the labour market at age 25 for those who have completed upper secondary education or lower as their highest educational level. Whilst completion of upper secondary education is widely regarded as being important, we find that early and lasting work experience…

  13. On the Derivation of Highest-Order Compact Finite Difference Schemes for the One- and Two-Dimensional Poisson Equation with Dirichlet Boundary Conditions

    KAUST Repository

    Settle, Sean O.; Douglas, Craig C.; Kim, Imbunm; Sheen, Dongwoo

    2013-01-01

    - and two-dimensional Poisson equation on uniform, quasi-uniform, and nonuniform face-to-face hyperrectangular grids and directly prove the existence or nonexistence of their highest-order local accuracies. Our derivations are unique in that we do not make

  14. DRUG INTERACTIONS WITH DIAZEPAM

    Directory of Open Access Journals (Sweden)

    Zoran Bojanić

    2011-06-01

    Full Text Available Diazepam is a benzodiazepine derivative with anxyolitic, anticonvulsant, hypnotic, sedative, skeletal muscle relaxant, antitremor, and amnestic activity. It is metabolized in the liver by the cytochrome P (CYP 450 enzyme system. Diazepam is N-demethylated by CYP3A4 and CYP2C19 to the active metabolite N-desmethyldiazepam, and is hydroxylated by CYP3A4 to the active metabolite temazepam. N-desmethyl-diazepam and temazepam are both further metabolized to oxazepam. Concomitant intake of inhibitors or inducers of the CYP isozymes involved in the biotransformation of diazepam may alter plasma concentrations of this drug, although this effect is unlikely to be associated with clinically relevant interactions.The goal of this article was to review the current literature on clinically relevant pharmacokinetic drug interactions with diazepam.A search of MEDLINE and EMBASE was conducted for original research and review articles published in English between January 1971. and May 2011. Among the search terms were drug interactions, diazepam, pharmacokinetics, drug metabolism, and cytochrome P450. Only articles published in peer-reviewed journals were included, and meeting abstracts were excluded. The reference lists of relevant articles were hand-searched for additional publications.Diazepam is substantially sorbed by the plastics in flexible containers, volume control set chambers, and tubings of intravenous administration sets. Manufacturers recommend not mixing with any other drug or solution in syringe or solution, although diazepam is compatible in syringe with cimetidine and ranitidine, and in Y-site with cisatracurium, dobutamine, fentanyl, hydromorphone, methadone, morphine, nafcillin, quinidine gluconate, remifentanil, and sufentanil. Diazepam is compatible with: dextrose 5% in water, Ringers injection, Ringers injection lactated and sodium chloride 0.9%. Emulsified diazepam is compatible with Intralipid and Nutralipid.Diazepam has low potential

  15. 21 CFR 146.146 - Frozen concentrated orange juice.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Frozen concentrated orange juice. 146.146 Section... Fruit Juices and Beverages § 146.146 Frozen concentrated orange juice. (a) Frozen concentrated orange juice is the food prepared by removing water from the juice of mature oranges as provided in § 146.135...

  16. 21 CFR 146.154 - Concentrated orange juice with preservative.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Concentrated orange juice with preservative. 146... Canned Fruit Juices and Beverages § 146.154 Concentrated orange juice with preservative. (a) Concentrated orange juice with preservative complies with the requirements for composition and labeling of optional...

  17. Exploiting Large-Scale Drug-Protein Interaction Information for Computational Drug Repurposing

    Science.gov (United States)

    2014-06-20

    studies that have reported antimalarial activities of azole compounds [39-43] lend support to our model predictions. The highest-scored non-malarial...Table 4, verapamil and cimetidine, do not have antimal- arial activities themselves but exhibit synergism when used in combination with antimalarial ... activators . Because of their high frequencies among the antimalarial drugs, according to Eq. 3, the drug-protein interactions contributing most to the

  18. Financial Burden of Cancer Drug Treatment in Lebanon.

    Science.gov (United States)

    Elias, Fadia; Khuri, Fadlo R; Adib, Salim M; Karam, Rita; Harb, Hilda; Awar, May; Zalloua, Pierre; Ammar, Walid

    2016-01-01

    The Ministry of Public Health (MOPH) in Lebanon provides cancer drugs free of charge for uninsured patients who account for more than half the total caseload. Other categories of cancer care are subsidized under more stringent eligibility criteria. MOPH's large database offers an excellent opportunity to analyze the cost of cancer treatment in Lebanon. Using utilization and spending data accumulated at MOPH during 20082013, the cost to the public budget of cancer drugs was assessed per case and per drug type. The average annual cost of cancer drugs was 6,475$ per patient. Total cancer drug costs were highest for breast cancer, followed by chronic myeloid leukemia (CML), colorectal cancer, lung cancer, and NonHodgkin's lymphoma (NHL), which together represented 74% of total MOPH cancer drug expenditure. The annual average cancer drug cost per case was highest for CML ($31,037), followed by NHL ($11,566). Trastuzumab represented 26% and Imatinib 15% of total MOPH cancer drug expenditure over six years. Sustained increase in cancer drug cost threatens the sustainability of MOPH coverage, so crucial for socially vulnerable citizens. To enhance the bargaining position with pharmaceutical firms for drug cost containment in a small market like Lebanon, drug price comparisons with neighboring countries which have already obtained lower prices may succeed in lowering drug costs.

  19. How to reliably deliver narrow individual-patient error bars for optimization of pacemaker AV or VV delay using a "pick-the-highest" strategy with haemodynamic measurements.

    Science.gov (United States)

    Francis, Darrel P

    2013-03-10

    Intuitive and easily-described, "pick-the-highest" is often recommended for quantitative optimization of AV and especially VV delay settings of biventricular pacemakers (BVP; cardiac resynchronization therapy, CRT). But reliable selection of the optimum setting is challenged by beat-to-beat physiological variation, which "pick-the-highest" combats by averaging multiple heartbeats. Optimization is not optimization unless the optimum is identified confidently. This document shows how to calculate how many heartbeats must be averaged to optimize reliably by pick-the-highest. Any reader, by conducting a few measurements, can calculate for locally-available methods (i) biological scatter between replicate measurements, and (ii) curvature of the biological response. With these, for any clinically-desired precision of optimization, the necessary number of heartbeats can be calculated. To achieve 95% confidence of getting within ±∆x of the true optimum, the number of heartbeats needed is 2(scatter/curvature)(2)/∆x(4) per setting. Applying published scatter/curvature values (which readers should re-evaluate locally) indicates that optimizing AV, even coarsely with a 40ms-wide band of precision, requires many thousand beats. For VV delay, the number approaches a million. Moreover, identifying the optimum twice as precisely requires 30-fold more beats. "Pick the highest" is quick to say but slow to do. We must not expect staff to do the impossible; nor criticise them for not doing so. Nor should we assume recommendations and published protocols are well-designed. Reliable AV or VV optimization, using "pick-the-highest" on commonly-recommended manual measurements, is unrealistic. Improving time-efficiency of the optimization process to become clinically realistic may need a curve-fitting strategy instead, with all acquired data marshalled conjointly. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  20. Photovoltaic concentrator module improvements study

    Energy Technology Data Exchange (ETDEWEB)

    Levy, S.L.; Kerschen, K.A. (Black and Veatch, Kansas City, MO (United States)); Hutchison, G. (Solar Kinetics, Inc., Dallas, TX (United States)); Nowlan, M.J. (Spire Corp., Bedford, MA (United States))

    1991-08-01

    This report presents results of a project to design and fabricate an improved photovoltaic concentrator module. Using previous work as a baseline, this study conducted analyses and testing to select major module components and design features. The lens parquet and concentrator solar cell were selected from the highest performing, available components. A single 185X point-focus module was fabricated by the project team and tested at Sandia. Major module characteristics include a 6 by 4 compression-molded acrylic lens parquet (0.737 m{sup 2} area), twenty-four 0.2 ohms-cm, FZ, p-Si solar cells (1.56 cm{sup 2} area) soldered to ceramic substrates and copper heat spreaders, and an aluminized steel housing with corrugated bottom. This project marked the first attempt to use prismatic covers on solar cells in a high-concentration, point-focus application. Cells with 15 percent metallization were obtained, but problems with the fabrication and placement of prismatic covers on these cells lead to the decision not to use covers in the prototype module. Cell assembly fabrication, module fabrication, and module optical design activities are presented here. Test results are also presented for bare cells, cell assemblies, and module. At operating conditions of 981 watts/m{sup 2} DNI and an estimated cell temperature of 65{degrees}C, the module demonstrated an efficiency of 13.9 percent prior to stressed environmental exposure. 12 refs., 56 figs., 7 tabs.

  1. Drug overdose surveillance using hospital discharge data.

    Science.gov (United States)

    Slavova, Svetla; Bunn, Terry L; Talbert, Jeffery

    2014-01-01

    We compared three methods for identifying drug overdose cases in inpatient hospital discharge data on their ability to classify drug overdoses by intent and drug type(s) involved. We compared three International Classification of Diseases, Ninth Revision, Clinical Modification code-based case definitions using Kentucky hospital discharge data for 2000-2011. The first definition (Definition 1) was based on the external-cause-of-injury (E-code) matrix. The other two definitions were based on the Injury Surveillance Workgroup on Poisoning (ISW7) consensus recommendations for national and state poisoning surveillance using the principal diagnosis or first E-code (Definition 2) or any diagnosis/E-code (Definition 3). Definition 3 identified almost 50% more drug overdose cases than did Definition 1. The increase was largely due to cases with a first-listed E-code describing a drug overdose but a principal diagnosis that was different from drug overdose (e.g., mental disorders, or respiratory or circulatory system failure). Regardless of the definition, more than 53% of the hospitalizations were self-inflicted drug overdoses; benzodiazepines were involved in about 30% of the hospitalizations. The 2011 age-adjusted drug overdose hospitalization rate in Kentucky was 146/100,000 population using Definition 3 and 107/100,000 population using Definition 1. The ISW7 drug overdose definition using any drug poisoning diagnosis/E-code (Definition 3) is potentially the highest sensitivity definition for counting drug overdose hospitalizations, including by intent and drug type(s) involved. As the states enact policies and plan for adequate treatment resources, standardized drug overdose definitions are critical for accurate reporting, trend analysis, policy evaluation, and state-to-state comparison.

  2. Drug Overdose Surveillance Using Hospital Discharge Data

    Science.gov (United States)

    Bunn, Terry L.; Talbert, Jeffery

    2014-01-01

    Objectives We compared three methods for identifying drug overdose cases in inpatient hospital discharge data on their ability to classify drug overdoses by intent and drug type(s) involved. Methods We compared three International Classification of Diseases, Ninth Revision, Clinical Modification code-based case definitions using Kentucky hospital discharge data for 2000–2011. The first definition (Definition 1) was based on the external-cause-of-injury (E-code) matrix. The other two definitions were based on the Injury Surveillance Workgroup on Poisoning (ISW7) consensus recommendations for national and state poisoning surveillance using the principal diagnosis or first E-code (Definition 2) or any diagnosis/E-code (Definition 3). Results Definition 3 identified almost 50% more drug overdose cases than did Definition 1. The increase was largely due to cases with a first-listed E-code describing a drug overdose but a principal diagnosis that was different from drug overdose (e.g., mental disorders, or respiratory or circulatory system failure). Regardless of the definition, more than 53% of the hospitalizations were self-inflicted drug overdoses; benzodiazepines were involved in about 30% of the hospitalizations. The 2011 age-adjusted drug overdose hospitalization rate in Kentucky was 146/100,000 population using Definition 3 and 107/100,000 population using Definition 1. Conclusion The ISW7 drug overdose definition using any drug poisoning diagnosis/E-code (Definition 3) is potentially the highest sensitivity definition for counting drug overdose hospitalizations, including by intent and drug type(s) involved. As the states enact policies and plan for adequate treatment resources, standardized drug overdose definitions are critical for accurate reporting, trend analysis, policy evaluation, and state-to-state comparison. PMID:25177055

  3. [Study of personal best value of peak expiratory flow in patients with asthma--comparison of the highest value of daily PEF under good control and the highest value of daily PEF obtained after using repeated inhaled beta2-agonist during high-dose inhaled steroid treatment].

    Science.gov (United States)

    Watanabe, Naoto; Makino, Sohei; Kihara, Norio; Fukuda, Takeshi

    2008-12-01

    In the guideline for asthma management, it is important to find the personal best value of peak expiratory flow (best PEF). Recently, we have substituted the highest value of PEF in daily life under good control (daily highest PEF) for the best PEF. In the present study, we considered whether the daily highest PEF could be used as the best PEF or not. Subjects were 30 asthmatics who were well controlled but whose baseline PEF values were less than 80 percent of predicted values. We compared the daily highest PEF and the highest of PEF obtained after repeated inhaled beta2-agonist (salbutamol MDI every 20 minutes three times). All subjects then received 1600 microg/day of beclomethasone dipropionate (BDP) for 4 to 8 weeks. We studied the effect of high-dose inhaled steroid treatment on each PEF value and compared the daily highest PEF and the highest PEF obtained after using repeated salbutamol MDI during high dose inhaled steroid therapy on the examination day again. The baseline PEF, daily highest PEF and the highest PEF obtained after salbutamol MDI were significantly less than the each values obtained after high-dose BDP. The best PEF value of them was the value obtained after repeated salbutamol MDI during high dose BDP. We suggest that the daily highest PEF under good control is not a substitute for best PEF because it changes according to the degree of improvement of airway inflammation. We recommend that a course of high dose inhaled steroid is effective in finding the best value of PEF for each individual with moderate asthma.

  4. Chitosan microspheres in novel drug delivery systems.

    Science.gov (United States)

    Mitra, Analava; Dey, Baishakhi

    2011-07-01

    The main aim in the drug therapy of any disease is to attain the desired therapeutic concentration of the drug in plasma or at the site of action and maintain it for the entire duration of treatment. A drug on being used in conventional dosage forms leads to unavoidable fluctuations in the drug concentration leading to under medication or overmedication and increased frequency of dose administration as well as poor patient compliance. To minimize drug degradation and loss, to prevent harmful side effects and to increase drug bioavailability various drug delivery and drug targeting systems are currently under development. Handling the treatment of severe disease conditions has necessitated the development of innovative ideas to modify drug delivery techniques. Drug targeting means delivery of the drug-loaded system to the site of interest. Drug carrier systems include polymers, micelles, microcapsules, liposomes and lipoproteins to name some. Different polymer carriers exert different effects on drug delivery. Synthetic polymers are usually non-biocompatible, non-biodegradable and expensive. Natural polymers such as chitin and chitosan are devoid of such problems. Chitosan comes from the deacetylation of chitin, a natural biopolymer originating from crustacean shells. Chitosan is a biocompatible, biodegradable, and nontoxic natural polymer with excellent film-forming ability. Being of cationic character, chitosan is able to react with polyanions giving rise to polyelectrolyte complexes. Hence chitosan has become a promising natural polymer for the preparation of microspheres/nanospheres and microcapsules. The techniques employed to microencapsulate with chitosan include ionotropic gelation, spray drying, emulsion phase separation, simple and complex coacervation. This review focuses on the preparation, characterization of chitosan microspheres and their role in novel drug delivery systems.

  5. Fenton-like reaction: a possible way to efficiently remove illicit drugs and pharmaceuticals from wastewater.

    Science.gov (United States)

    Mackuľak, Tomáš; Mosný, Michal; Grabic, Roman; Golovko, Oksana; Koba, Olga; Birošová, Lucia

    2015-03-01

    We analyzed 13 psychoactive pharmaceuticals, illicit drugs and their metabolites in wastewater treatment plant influent and effluent and the possibility of their degradation by biological and chemical processes. Tramadol (413-853 ng/L) and methamphetamine (460-682 ng/L) were the most concentrated compounds in the wastewater in winter and summer, respectively. A significant decrease in the concentration of tramadol in wastewater was measured during the summer. The lowest efficiency was observed for tramadol, venlafaxine, citalopram and oxazepam (∼ 10%) and the highest efficiency was observed for amphetamine and THC-COOH (∼ 80%). The efficiency of compound degradation via the Fenton reaction, a modified Fenton reaction and different degradation (by algae, wood-rotting fungi and enzymes at influent versus effluent) was determined. The Fenton reaction and its modification were efficient at eliminating these substances in comparison with the tested biological processes. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Personality, Drug Preference, Drug Use, and Drug Availability

    Science.gov (United States)

    Feldman, Marc; Boyer, Bret; Kumar, V. K.; Prout, Maurice

    2011-01-01

    This study examined the relationship between drug preference, drug use, drug availability, and personality among individuals (n = 100) in treatment for substance abuse in an effort to replicate the results of an earlier study (Feldman, Kumar, Angelini, Pekala, & Porter, 2007) designed to test prediction derived from Eysenck's (1957, 1967)…

  7. The Research Progress of Targeted Drug Delivery Systems

    Science.gov (United States)

    Zhan, Jiayin; Ting, Xizi Liang; Zhu, Junjie

    2017-06-01

    Targeted drug delivery system (DDS) means to selectively transport drugs to targeted tissues, organs, and cells through a variety of drugs carrier. It is usually designed to improve the pharmacological and therapeutic properties of conventional drugs and to overcome problems such as limited solubility, drug aggregation, poor bio distribution and lack of selectivity, controlling drug release carrier and to reduce normal tissue damage. With the characteristics of nontoxic and biodegradable, it can increase the retention of drug in lesion site and the permeability, improve the concentration of the drug in lesion site. at present, there are some kinds of DDS using at test phase, such as slow controlled release drug delivery system, targeted drug delivery systems, transdermal drug delivery system, adhesion dosing system and so on. This paper makes a review for DDS.

  8. Análise comparativa da concentração industrial e de turnover da indústria farmacêutica no Brasil para os segmentos de medicamentos de marca e genéricos Comparative analysis of the Industrial Concentration and Turnover of the pharmaceutical industry in Brazil for the segments of mark and generic drugs

    Directory of Open Access Journals (Sweden)

    Gerson Rosenberg

    2010-04-01

    Full Text Available Este artigo analisa a evolução da estrutura do segmento de medicamentos de marca e genéricos no Brasil a partir de 1997. Após a entrada dos medicamentos genéricos, constatou-se que não houve diminuição significativa da concentração na indústria farmacêutica brasileira, porém, o mesmo não ocorreu em nível mundial, verificando-se um aumento da concentração a partir de 2001, impulsionado pelo expressivo processo de fusões e aquisições nos últimos anos da década de 1990. Em relação ao turnover, notou-se que este foi muito baixo para o grupo das maiores empresas em ambos os segmentos de medicamentos. Entretanto, observa-se um elevado turnover com a entrada dos genéricos, mostrando o fortalecimento da indústria nacional. Verifica-se que o processo de fusões e aquisições entre empresas nacionais é pouco significativo, o que pode ser uma alternativa para as pequenas empresas farmacêuticas aumentarem a sua participação no mercado brasileiro.This paper analyzes the evolution of brand-name and generic drugs structure in Brazil since 1997. After the introduction of generic drugs it was not verified a significant decrease in the concentration of Brazilian pharmaceutical industry. The process of mergers and acquisitions in the 90's enhanced the process of concentration in the international market. However, a non-expressive turnover can be demonstrated in both pharmaceutical and generic markets. At the same time, the entrance of the generic industry in Brazil explains the invigoration of the national industry. The mergers and acquisitions process in the pharmaceutical industry is quite intense in Europe and in the USA, although in Brazil it is still not significant.

  9. Tocopheryl pullulan-based self assembling nanomicelles for anti-cancer drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jingyun, E-mail: wangjingyun67@dlut.edu.cn [School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024 (China); Cui, Shuang [School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024 (China); Bao, Yongming, E-mail: biosci@dlut.edu.cn [School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024 (China); Xing, Jishuang [School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024 (China); Hao, Wenbo [Department of Physics and Chemistry, Heihe University, Heihe 164300 (China)

    2014-10-01

    Amphiphilic α-tocopherol pullulan polymers (PUTC1, PUTC2, and PUTC3) with different degrees of substitution were synthesized as new carriers for anticancer drugs. The polymers easily self-assembled into nanomicelles through dialysis method. The critical micelle concentrations (CMCs) were 38.0, 8.0, and 4.3 mg/L for PUTC1, PUTC2, and PUTC3, respectively. 10-Hydroxycamptothecin (HCPT) used as a model drug was successfully loaded into the PUTC nanomicelles. Transmission electron microscopy images demonstrated that HCPT-loaded PUTC nanomicelles were almost spherical and had sizes ranging within 171.5–257.8 nm that increased with increased HCPT-loading content, as determined by dynamic laser scattering. The highest encapsulation efficiency of HCPT in PUTC nanomicelles reached 98.3%. The in vitro release of HCPT from PUTC micelles demonstrated sustained release for over 80 h. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays showed that blank PUTC micelles were nontoxic to normal cells and that the HCPT-loaded PUTC2 nanomicelles showed higher cytotoxicity than the free drug, which was attributed to the enhanced cellular uptake of drug-loaded nanomicelles. Biodistribution experiments showed that PUTC micelles provided an excellent approach to rapid drug transport into cell nuclei. Moreover, the cellular uptake of micelles was found to be an energy-dependent and actin polymerization-associated endocytic process by endocytosis inhibition experiments. These results suggested that PUTC nanomicelles had considerable potential as a drug carrier for drug intracellular delivery in cancer therapy. - Highlights: • Tocopheryl pullulan-based (PUTC) self-assembling nanomicelles were fabricated. • These micelles showed low CMC and dispersed uniformly with regular spherical shape. • High entrapment efficiency and in vitro sustained release of HCPT in PUTC micelles • HCPT–PUTC micelles accumulated in cell nuclei and showed higher anticancer activity.

  10. Tocopheryl pullulan-based self assembling nanomicelles for anti-cancer drug delivery

    International Nuclear Information System (INIS)

    Wang, Jingyun; Cui, Shuang; Bao, Yongming; Xing, Jishuang; Hao, Wenbo

    2014-01-01

    Amphiphilic α-tocopherol pullulan polymers (PUTC1, PUTC2, and PUTC3) with different degrees of substitution were synthesized as new carriers for anticancer drugs. The polymers easily self-assembled into nanomicelles through dialysis method. The critical micelle concentrations (CMCs) were 38.0, 8.0, and 4.3 mg/L for PUTC1, PUTC2, and PUTC3, respectively. 10-Hydroxycamptothecin (HCPT) used as a model drug was successfully loaded into the PUTC nanomicelles. Transmission electron microscopy images demonstrated that HCPT-loaded PUTC nanomicelles were almost spherical and had sizes ranging within 171.5–257.8 nm that increased with increased HCPT-loading content, as determined by dynamic laser scattering. The highest encapsulation efficiency of HCPT in PUTC nanomicelles reached 98.3%. The in vitro release of HCPT from PUTC micelles demonstrated sustained release for over 80 h. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays showed that blank PUTC micelles were nontoxic to normal cells and that the HCPT-loaded PUTC2 nanomicelles showed higher cytotoxicity than the free drug, which was attributed to the enhanced cellular uptake of drug-loaded nanomicelles. Biodistribution experiments showed that PUTC micelles provided an excellent approach to rapid drug transport into cell nuclei. Moreover, the cellular uptake of micelles was found to be an energy-dependent and actin polymerization-associated endocytic process by endocytosis inhibition experiments. These results suggested that PUTC nanomicelles had considerable potential as a drug carrier for drug intracellular delivery in cancer therapy. - Highlights: • Tocopheryl pullulan-based (PUTC) self-assembling nanomicelles were fabricated. • These micelles showed low CMC and dispersed uniformly with regular spherical shape. • High entrapment efficiency and in vitro sustained release of HCPT in PUTC micelles • HCPT–PUTC micelles accumulated in cell nuclei and showed higher anticancer activity.

  11. Five-year update on the occurrence of alcohol and other drugs in blood samples from drivers killed in road-traffic crashes in Sweden.

    Science.gov (United States)

    Jones, Alan Wayne; Kugelberg, Fredrik C; Holmgren, Anita; Ahlner, Johan

    2009-04-15

    According to statistics provided by the Swedish National Road Administration (Vägverket), a total of 1403 drivers were killed in road-traffic crashes in Sweden between 2003 and 2007. Forensic autopsies were performed in approximately 97% of all deaths and specimens of blood and urine were sent for toxicological analysis. In 60% of cases (N=835) the toxicology results were negative and 83% of these victims were men. The blood-alcohol concentration (BAC) was above the legal limit for driving (>0.2g/L) in 22% of cases (N=315) at mean, median and highest concentrations of 1.7 g/L, 1.7 g/L and 4.9 g/L, respectively. The proportions of male to female drivers with BAC>0.2g/L were 93% vs 7% compared with 83% vs 17% for those with drugs other than alcohol in blood. Drivers with a punishable BAC were over-represented in single vehicle crashes compared with multiple vehicle crashes (67% vs 33%). The opposite held for drivers who had taken a prescription drug (39% vs 61%) and also for drug-negative cases (31% vs 69%). Drugs other than alcohol were identified in 253 cases (18%); illicit drugs only in 39 cases (2.8%), both licit and illicit in 28 cases (2.0%) and in 186 cases (13.3%) one or more therapeutic drugs were present. Amphetamine was the most common illicit drug identified at mean, median and highest concentrations of 1.5mg/L, 1.1mg/L and 5.0mg/L, respectively (N=39). Blood specimens contained a wide spectrum of pharmaceutical products (mean 2.4 drugs/person), comprising sedative-hypnotics (N=93), opiates/opioids (N=69) as well non-scheduled substances, such as paracetamol (N=78) and antidepressants (N=93). The concentrations of these substances in blood were mostly in the therapeutic range. Despite an appreciable increase (12-fold) in number of arrests made by the police for drug-impaired driving after a zero-tolerance law was introduced (July 1999), alcohol still remains the psychoactive substance most frequently identified in the blood of drivers killed in road

  12. Polymorphic drug metabolising enzymes : Assessment of activities by phenotyping and genotyping in clinical pharmacology

    NARCIS (Netherlands)

    Tamminga, Willem Jan

    2001-01-01

    Drug effects (pharmacodynamics) are determined by drug concentration at target site and the affinity of the drug for a target. Pharmacogenetics describes inherited differences in drug metabolising enzyme activities and differences in drug transporters and receptors.Answers were sought on the

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

    Science.gov (United States)

    Negus, S Stevens; Banks, Matthew L

    2016-08-30

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

  14. Metal concentrations in selected organs and tissues of five Red ...

    African Journals Online (AJOL)

    The absence of metalprocessing industries in the catchments of the Florida Lake and the Steynsrus farm dams reflects the low liver and kidney concentrations of Cd, Ni and Cu, respectively. The blood of the Natalspruit wetland coots contained the highest dry weight concentrations of Ni (11.4 mg/g), Cd (1.8 mg/g) and Cu ...

  15. Ultra flat ideal concentrators of high concentration

    Energy Technology Data Exchange (ETDEWEB)

    Chaves, Julio [IST, Physics Dept., Lisboa (Portugal); INETI-DER, Lisboa (Portugal); Collares-Pereira, Manuel [INETI-DER, Lisboa (Portugal)

    2000-07-01

    A new method for the design of nonimaging devices is presented. Its application to the design of ultra flat compact concentrators is analysed. These new concentrators are based on a combination of two stages: the first one is composed of a large number of small structures placed side by side and the second one is a very compact single device concentrating the radiation to the limit. These devices are ideal for 2D. These compact designs are much more compact than the traditional ones like lens-mirror combinations or parabolic primaries with nonimaging secondaries. Besides, they can be designed for any acceptance angle, while the traditional ones are limited to small acceptance angles. (Author)

  16. Simplifying consent for HIV testing is associated with an increase in HIV testing and case detection in highest risk groups, San Francisco January 2003-June 2007.

    Directory of Open Access Journals (Sweden)

    Nicola M Zetola

    2008-07-01

    Full Text Available Populations at highest risk for HIV infection face multiple barriers to HIV testing. To facilitate HIV testing procedures, the San Francisco General Hospital Medical Center eliminated required written patient consent for HIV testing in its medical settings in May 2006. To describe the change in HIV testing rates in different hospital settings and populations after the change in HIV testing policy in the SFDH medical center, we performed an observational study using interrupted time series analysis.Data from all patients aged 18 years and older seen from January 2003 through June 2007 at the San Francisco Department of Public Health (SFDPH medical care system were included in the analysis. The monthly HIV testing rate per 1000 had patient-visits was calculated for the overall population and stratified by hospital setting, age, sex, race/ethnicity, homelessness status, insurance status and primary language.By June 2007, the average monthly rate of HIV tests per 1000 patient-visits increased 4.38 (CI, 2.17-6.60, p<0.001 over the number predicted if the policy change had not occurred (representing a 44% increase. The monthly average number of new positive HIV tests increased from 8.9 (CI, 6.3-11.5 to 14.9 (CI, 10.6-19.2, p<0.001, representing a 67% increase. Although increases in HIV testing were seen in all populations, populations at highest risk for HIV infection, particularly men, the homeless, and the uninsured experienced the highest increases in monthly HIV testing rates after the policy change.The elimination of the requirement for written consent in May 2006 was associated with a significant and sustained increase in HIV testing rates and HIV case detection in the SFDPH medical center. Populations facing the higher barriers to HIV testing had the highest increases in HIV testing rates and case detection in response to the policy change.

  17. Drug adsorption to plastic containers and retention of drugs in cultured cells under in vitro conditions.

    Science.gov (United States)

    Palmgrén, Joni J; Mönkkönen, Jukka; Korjamo, Timo; Hassinen, Anssi; Auriola, Seppo

    2006-11-01

    Loss of drug content during cell culture transport experiment can lead to misinterpretations in permeability analysis. This study analyses drug adsorption to various plastic containers and drug retention in cultured cells under in vitro conditions. The loss of various drugs to polystyrene tubes and well plates was compared to polypropylene and glass tubes both in deionised water and buffer solution. In cellular uptake experiments, administered drugs were obtained from cultured cells by liquid extraction. Samples were collected at various time points and drug concentrations were measured by a new HPLC-MS/MS method. Acidic drugs (hydrochlorothiazide, naproxen, probenicid, and indomethacin) showed little if any sorption to all tested materials in either water or buffer. In the case of basic drugs, substantial loss to polystyrene tubes and well plates was observed. After 4.5 h, the relative amount remaining in aqueous test solution stored in polystyrene tubes was 64.7 +/- 6.8%, 38.4 +/- 9.1%, 31.9 +/- 6.7%, and 23.5 +/- 6.1% for metoprolol, medetomidine, propranolol, and midazolam, respectively. Interestingly, there was no significant loss of drugs dissolved in buffer to any of the tested materials indicating that buffer reduced surficial interaction. The effect of drug concentration to sorption was also tested. Results indicated that the higher the concentration in the test solution the lower the proportional drug loss, suggesting that the polystyrene contained a limited amount of binding sites. Cellular uptake studies showed considerable retention of drugs in cultured cells. The amounts of absorbed drugs in cellular structures were 0.45%, 4.88%, 13.15%, 43.80%, 23.57% and 11.22% for atenolol, metoprolol, medetomidine, propranolol, midazolam, and diazepam, respectively. Overall, these findings will benefit development and validation of further in vitro drug permeation experiments.

  18. Application of gold nanoparticles for improved drug efficiency

    Science.gov (United States)

    Shittu, K. O.; Bankole, M. T.; Abdulkareem, A. S.; Abubakre, O. K.; Ubaka, A. U.

    2017-09-01

    Due to increasing resistance of microorganisms towards current antibiotics, there is a need for new or enhanced antibiotics. Nanotechnology is a technology that enhances the use of gold nanoparticles (AuNP) in area of medical applications, especially as a drug carrier for targeted drug delivery. In this research, AuNPs was synthesized using biological method via bioreduction of Piper guineense aqueous leaf extract on tetra gold chloride, characterized using UV-Vis spectrophometer, DLS, TEM/EDS and FTIR. The synthesized AuNPs was covalently functionalized with polyethylene glycol and encapsulated with Lincomycin and in vitro dissolution methods was used to evaluate the potential performance of the formulated nanodrug. The nanodrug has highest release efficiency at the 9th minutes (23.4 mg ml-1 for 40 °C) and (29.5 mg ml-1 for 60 °C) compared with the non-nanodrug. The antibacterial potential of the nanodrug was seen on the gram-positive bacteria of Staphylococcus aureus and Streptococcus pyogenes with highest inhibitions of 18 mm (at 40 °C) and 16 mm (at 60 °C) for S. aureus, and 16 mm for S. pyogenes (both at 40 °C and 60 °C). The bacteria growth inhibition continued and lasted for 15 min, while that of non-nanodrug lasted for 9 min with lesser growth inhibition compared to the formulated nanodrug. This work shows that the presence of the AuNPs increased the release efficiency of lincomycin even at a lower concentration and also bacteria growth inhibition thereby suggesting the effectiveness of the nanodrug formulation.

  19. Drugs Approved for Rhabdomyosarcoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for rhabdomyosarcoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries. There may be drugs used in rhabdomyosarcoma that are not listed here.

  20. Information for Consumers (Drugs)

    Science.gov (United States)

    ... approved drugs Drugs@FDA Information on FDA-approved brand name and generic drugs including labeling and regulatory history Drugs with Approved Risk Evaluation and Mitigation Strategies (REMS) REMS is a risk management plan required by FDA for certain prescription drugs, ...

  1. Drugs and lactation

    International Nuclear Information System (INIS)

    Kelssering, G.; Aguiar, L.F.; Ribeiro, R.M.; Souza, A.Z. de

    1988-01-01

    Different kinds of drugs who can be transferred through the mother's milk to the lactant and its effects are showed in this work. A list of them as below: cardiotonics, diuretics, anti-hypertensives, beta-blockings, anti-arrythmics, drugs with gastrintestinal tract action, hormones, antibiotics and chemotherapeutics, citostatic drugs, central nervous system action drugs and anticoagulants drugs. (L.M.J.) [pt

  2. Supported rhodium catalysts for ammonia-borane hydrolysis. Dependence of the catalytic activity on the highest occupied state of the single rhodium atoms

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Liangbing; Li, Hongliang; Zhang, Wenbo; Zhao, Xiao; Qiu, Jianxiang; Li, Aowen; Zheng, Xusheng; Zeng, Jie [Hefei National Lab. for Physical Sciences at the Microscale, Key Lab. of Strongly-Coupled Quantum Matter Physics, Chinese Academy of Sciences, Hefei, Anhui(China); Department of Chemical Physics, University of Science and Technology of China, Hefei, Anhui (China); Hu, Zhenpeng [School of Physics, Nankai University, Tianjin (China); Si, Rui [Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Sciences (China)

    2017-04-18

    Supported metal nanocrystals have exhibited remarkable catalytic performance in hydrogen generation reactions, which is influenced and even determined by their supports. Accordingly, it is of fundamental importance to determine the direct relationship between catalytic performance and metal-support interactions. Herein, we provide a quantitative profile for exploring metal-support interactions by considering the highest occupied state in single-atom catalysts. The catalyst studied consisted of isolated Rh atoms dispersed on the surface of VO{sub 2} nanorods. It was observed that the activation energy of ammonia-borane hydrolysis changed when the substrate underwent a phase transition. Mechanistic studies indicate that the catalytic performance depended directly on the highest occupied state of the single Rh atoms, which was determined by the band structure of the substrates. Other metal catalysts, even with non-noble metals, that exhibited significant catalytic activity towards NH{sub 3}BH{sub 3} hydrolysis were rationally designed by adjusting their highest occupied states. (copyright 2017 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

  3. Highly concentrating Fresnel lenses

    International Nuclear Information System (INIS)

    Kritchman, E.M.; Friesem, A.A.; Yekutieli, G.

    1979-01-01

    A new type of concave Fresnel lens capable of concentrating solar radiation very near the ultimate concentration limit is considered. The differential equations that describe the lens are solved to provide computed solutions which are then checked by ray tracing techniques. The performance (efficiency and concentration) of the lens is investigated and compared to that of a flat Fresnel lens, showing that the new lens is preferable for concentrating solar radiation. (author)

  4. Assessment of simvastatin niosomes for pediatric transdermal drug delivery.

    Science.gov (United States)

    Zidan, Ahmed S; Hosny, Khaled M; Ahmed, Osama A A; Fahmy, Usama A

    2016-06-01

    The prevalence of childhood dyslipidemia increases and is considered as an important risk factor for the incidence of cardiovascular disease in the adulthood. To improve dosing accuracy and facilitate the determination of dosing regimens in function of the body weight, the proposed study aims at preparing transdermal niosomal gels of simvastatin as possible transdermal drug delivery system for pediatric applications. Twelve formulations were prepared to screen the influence of formulation and processing variables on critical niosomal characteristics. Nano-sized niosomes with 0.31 μm number-weighted size displayed highest simvastatin release rate with 8.5% entrapment capacity. The niosomal surface coverage by negative charges was calculated according to Langmuir isotherm with n = 0.42 to suggest that the surface association was site-independent, probably producing surface rearrangements. Hypolipidemic activities after transdermal administration of niosomal gels to rats showed significant reduction in cholesterol and triglyceride levels while increasing plasma high-density lipoproteins concentration. Bioavailability estimation in rats revealed an augmentation in simvastatin bioavailability by 3.35 and 2.9 folds from formulation F3 and F10, respectively, compared with oral drug suspension. Hence, this transdermal simvastatin niosomes not only exhibited remarkable potential to enhance its bioavailability and hypolipidemic activity but also considered a promising pediatric antihyperlipidemic formulation.

  5. Solar cell concentrating system

    International Nuclear Information System (INIS)

    Garg, H.P.; Sharma, V.K.; Agarwal, R.K.

    1986-11-01

    This study reviews fabrication techniques and testing facilities for different solar cells under concentration which have been developed and tested. It is also aimed to examine solar energy concentrators which are prospective candidates for photovoltaic concentrator systems. This may provide an impetus to the scientists working in the area of solar cell technology

  6. Rheology of concentrated biomass

    Science.gov (United States)

    J.R. Samaniuk; J. Wang; T.W. Root; C.T. Scott; D.J. Klingenberg

    2011-01-01

    Economic processing of lignocellulosic biomass requires handling the biomass at high solids concentration. This creates challenges because concentrated biomass behaves as a Bingham-like material with large yield stresses. Here we employ torque rheometry to measure the rheological properties of concentrated lignocellulosic biomass (corn stover). Yield stresses obtained...

  7. Hydrogel-Forming Microneedle Arrays Allow Detection of Drugs and Glucose In Vivo: Potential for Use in Diagnosis and Therapeutic Drug Monitoring.

    Directory of Open Access Journals (Sweden)

    Ester Caffarel-Salvador

    Full Text Available We describe, for the first time the use of hydrogel-forming microneedle (MN arrays for minimally-invasive extraction and quantification of drug substances and glucose from skin in vitro and in vivo. MN prepared from aqueous blends of hydrolysed poly(methyl-vinylether-co-maleic anhydride (11.1% w/w and poly(ethyleneglycol 10,000 daltons (5.6% w/w and crosslinked by esterification swelled upon skin insertion by uptake of fluid. Post-removal, theophylline and caffeine were extracted from MN and determined using HPLC, with glucose quantified using a proprietary kit. In vitro studies using excised neonatal porcine skin bathed on the underside by physiologically-relevant analyte concentrations showed rapid (5 min analyte uptake. For example, mean concentrations of 0.16 μg/mL and 0.85 μg/mL, respectively, were detected for the lowest (5 μg/mL and highest (35 μg/mL Franz cell concentrations of theophylline after 5 min insertion. A mean concentration of 0.10 μg/mL was obtained by extraction of MN inserted for 5 min into skin bathed with 5 μg/mL caffeine, while the mean concentration obtained by extraction of MN inserted into skin bathed with 15 μg/mL caffeine was 0.33 μg/mL. The mean detected glucose concentration after 5 min insertion into skin bathed with 4 mmol/L was 19.46 nmol/L. The highest theophylline concentration detected following extraction from a hydrogel-forming MN inserted for 1 h into the skin of a rat dosed orally with 10 mg/kg was of 0.363 μg/mL, whilst a maximum concentration of 0.063 μg/mL was detected following extraction from a MN inserted for 1 h into the skin of a rat dosed with 5 mg/kg theophylline. In human volunteers, the highest mean concentration of caffeine detected using MN was 91.31 μg/mL over the period from 1 to 2 h post-consumption of 100 mg Proplus® tablets. The highest mean blood glucose level was 7.89 nmol/L detected 1 h following ingestion of 75 g of glucose, while the highest mean glucose concentration

  8. Assessment of radioactivity concentrations and effective of ...

    African Journals Online (AJOL)

    They find their ways in to the plants through the leaves and absorption of nutrients and water from the soil through the roots. ... The highest concentrations of 40K, 238U and 232Th were from pineapple of value 102.36 ± 10.81Bqkg-1, orange of value 12.18 ± 4.36Bqkg-1 and mango of value 8.01 ± 3.25 Bqkg-1 respectively.

  9. Triple-component nanocomposite films prepared using a casting method: Its potential in drug delivery

    Directory of Open Access Journals (Sweden)

    Sadia Gilani

    2018-04-01

    Full Text Available The purpose of this study was to fabricate a triple-component nanocomposite system consisting of chitosan, polyethylene glycol (PEG, and drug for assessing the application of chitosan–PEG nanocomposites in drug delivery and also to assess the effect of different molecular weights of PEG on nanocomposite characteristics. The casting/solvent evaporation method was used to prepare chitosan–PEG nanocomposite films incorporating piroxicam-β-cyclodextrin. In order to characterize the morphology and structure of nanocomposites, X-ray diffraction technique, scanning electron microscopy, thermogravimetric analysis, and Fourier transmission infrared spectroscopy were used. Drug content uniformity test, swelling studies, water content, erosion studies, dissolution studies, and anti-inflammatory activity were also performed. The permeation studies across rat skin were also performed on nanocomposite films using Franz diffusion cell. The release behavior of films was found to be sensitive to pH and ionic strength of release medium. The maximum swelling ratio and water content was found in HCl buffer pH 1.2 as compared to acetate buffer of pH 4.5 and phosphate buffer pH 7.4. The release rate constants obtained from kinetic modeling and flux values of ex vivo permeation studies showed that release of piroxicam-β-cyclodextrin increased with an increase in concentration of PEG. The formulation F10 containing 75% concentration of PEG showed the highest swelling ratio (3.42±0.02 in HCl buffer pH 1.2, water content (47.89±1.53% in HCl buffer pH 1.2, maximum cumulative drug permeation through rat skin (2405.15±10.97 μg/cm2 in phosphate buffer pH 7.4, and in vitro drug release (35.51±0.26% in sequential pH change mediums, and showed a significantly (p<0.0001 higher anti-inflammatory effect (0.4 cm. It can be concluded from the results that film composition had a particular impact on drug release properties. The different molecular weights of PEG have a

  10. Can medical students calculate drug doses? | Harries | Southern ...

    African Journals Online (AJOL)

    ... with calculations when the drug concentration was expressed either as a ratio or a percentage. Conclusion: Our findings support calls for the standardised labelling of drugs in solution and for dosage calculation training in the medical curriculum. Keywords: drug dosage calculations, clinical competence, medication errors

  11. Effect of paracentesis on ocular cloxacillin concentration

    International Nuclear Information System (INIS)

    Salminen, L.

    1978-01-01

    The effect of interior chamber puncture on cloxacillin concentration in the rabbit eye after intravenous injection was studied using a radioactive tracer method. The enhancement in drug concentration caused by paracentesis was most immediate and significant in the iris-ciliary body preparation. It was soon followed by high cloxacillin concentration in the aqueous humour, which contributed to elevated cloxacillin levels in the cornea, lens and anterior vitreous body, when compared to normal material. Contrary to normal eyes, cloxacillin concentration in the cornea of the punctured eyes was higher than in the limbal area. The morphological changes occurring after paracentesis are discussed. The breakdown of the hydrodynamic equilibrium in the eye, suggested as the only change after paracentesis by Raviola (1974), cannot merely explain the cloxacillin concentration changes measured in the punctured eye. (author)

  12. Drug Retention Times

    Energy Technology Data Exchange (ETDEWEB)

    Center for Human Reliability Studies

    2007-05-01

    The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user.

  13. Drug Reactions - Multiple Languages

    Science.gov (United States)

    ... PDF Drug Interactions - HIV medicines, part 6 - English MP3 Drug Interactions - HIV medicines, part 6 - 简体中文 (Chinese, Simplified (Mandarin dialect)) MP3 Drug Interactions - HIV medicines, part 6 - English MP4 ...

  14. Teenagers and drugs

    Science.gov (United States)

    Teenagers and drugs; Symptoms of drug use in teenagers; Drug abuse - teenagers; Substance abuse - teenagers ... for a specialist who has experience working with teenagers. Do not hesitate, get help right away. The ...

  15. Drug Interaction API

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Interaction API is a web service for accessing drug-drug interactions. No license is needed to use the Interaction API. Currently, the API uses DrugBank for its...

  16. Effect of intravenous drug administration mode on drug distribution in a tumor slab: a finite Fourier transform analysis.

    Science.gov (United States)

    Subramaniam, B; Claudius, J S

    1990-03-08

    Cancer therapy using chemotherapeutic drugs frequently involves injection of the drug into the body through some intravenous mode of administration, viz, continuous (drip) infusion or single/multiple bolus injection(s). An understanding of the effect of the various modes of administration upon tumor penetration of drug is essential to rational design of drug therapy. This paper investigates drug penetration into a model tumor of slab geometry (between two capillaries) in which the overall transport rate of drug is limited by intra-tumor transport characterized by an effective diffusion coefficient. Employing the method of Finite Fourier Transforms (FFT), analytical solutions have been obtained for transient drug distribution in both the plasma and the tumor following three modes of administration, viz, continuous infusion, single bolus injection and equally-spaced equal-dose multiple bolus injections, of a given amount of drug. The qualitative trends exhibited by the plasma drug distribution profiles are consistent with reported experimental studies. Two concepts, viz, the dimensionless decay constant and the plasma/tumor drug concentration trajectories, are found to be particularly useful in the rational design of drug therapy. The dimensionless decay constant provides a measure of the rate of drug decay in the plasma relative to the rate of drug diffusion into the tumor and is thus characteristic of the tumor/drug system. The magnitude of this parameter dictates the choice of drug administration mode for minimizing drug decay in the plasma while simultaneously maximizing drug transport into the tumor. The concentration trajectories provide a measure of the plasma drug concentration relative to the tumor drug concentration at various times following injection. When the tumor drug concentration exceeds the plasma drug concentration, the drug will begin to diffuse out of the tumor. Knowledge of the time at which this diffusion reversal occurs is especially useful

  17. Drug-drug interactions as a determinant of elevated lithium serum levels in daily clinical practice

    NARCIS (Netherlands)

    Wilting, [No Value; Movig, KL; Moolenaar, M; Hekster, YA; Brouwers, [No Value; Heerdink, ER; Nolen, WA; Egberts, AC

    Objective: Lithium is a drug with a narrow therapeutic window. Concomitantly used medication is a potentially influencing factor of lithium serum concentrations. We conducted a multicentre retrospective case-control study with the aim of investigating lithium-related drug interactions as

  18. The influence of drug distribution and drug-target binding on target occupancy : The rate-limiting step approximation

    NARCIS (Netherlands)

    Witte, de W.E.A.; Vauquelin, G.; Graaf, van der P.H.; Lange, de E.C.M.

    2017-01-01

    The influence of drug-target binding kinetics on target occupancy can be influenced by drug distribution and diffusion around the target, often referred to as "rebinding" or "diffusion-limited binding". This gives rise to a decreased decline of the drug-target complex concentration as a result of a

  19. Pulmonary toxicity of cytostatic drugs: cell kinetics

    International Nuclear Information System (INIS)

    Witschi, H.; Godfrey, G.; Frome, E.; Lindenschmidt, R.C.

    1987-01-01

    Mice were treated with three cytostatic drugs: cyclophosphamide, busulfan, or 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). The alveolar labeling index was measured following drug administration with a pulse of 3 H-labeled thymidine and autoradiography. In cyclophosphamide-treated animals, peak alveolar cell proliferation was seen 5 days after injection of the drug. In animals treated with busulfan or BCNU, proliferation was even more delayed (occurring 2-3 weeks after administration). In contrast, with oleic acid, the highest alveolar cell labeling was found 2 days after intravenous administration. In animals exposed to a cytostatic drug, proliferation of type II alveolar cells was never a prominent feature whereas in animals treated with oleic acid there was an initial burst of type II cell proliferation. It is concluded that the patterns of pulmonary repair vary between chemicals designed to interfere with DNA replication as compared to agents which produce acute lung damage such as oleic acid

  20. Adult Cigarette Smokers at Highest Risk for Concurrent Alternative Tobacco Product Use Among a Racially/Ethnically and Socioeconomically Diverse Sample.

    Science.gov (United States)

    Nollen, Nicole L; Ahluwalia, Jasjit S; Lei, Yang; Yu, Qing; Scheuermann, Taneisha S; Mayo, Matthew S

    2016-04-01

    Rates of alternative tobacco product use (ATPs; eg, cigars, cigarillos, pipes) among cigarette smokers are on the rise but little is known about the subgroups at highest risk. This study explored interactions between demographic, tobacco, and psychosocial factors to identify cigarette smokers at highest risk for ATP use from a racially/ethnically and socioeconomically diverse sample of adult smokers across the full smoking spectrum (nondaily, daily light, daily heavy). Two-thousand three-hundred seventy-six adult cigarette smokers participated in an online cross-sectional survey. Quotas ensured equal recruitment of African American (AA), white (W), Hispanic/Latino (H) as well as daily and nondaily smokers. Classification and Regression Tree modeling was used to identify subgroups of cigarette smokers at highest risk for ATP use. 51.3% were Cig+ATP smokers. Alcohol for men and age, race/ethnicity, and discrimination for women increased the probability of ATP use. Strikingly, 73.5% of men screening positive for moderate to heavy drinking and 62.2% of younger (≤45 years) African American/Hispanic/Latino women who experienced regular discrimination were Cig+ATP smokers. Screening for concurrent ATP use is necessary for the continued success of tobacco cessation efforts especially among male alcohol users and racial/ethnic minority women who are at greatest risk for ATP use. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Interaction of cephalosporin drugs with dodecyltrimethylammonium Bromide

    International Nuclear Information System (INIS)

    Hoque, Md. Anamul; Hossain, Mohammed Delwar; Khan, Mohammed Abdullah

    2013-01-01

    Highlights: • We carry out the interaction of cephalosporin drugs with DTAB conductometrically. • We examine the effect of drugs on the critical micelle concentration of DTAB. • Three critical micelle concentrations are obtained for drug- DTAB system. • Electrostatic and hydrophobic interactions between drugs and DTAB are proposed. • Drug supported micelle formation of DTAB is much favoured in aq. solution of K 2 SO 4 . -- Abstract: The interaction of three cephalosporin drugs namely cefadroxyl monohydrate (CFM), cephalexin monohydrate (CLM) and cephradine monohydrate (CDM) with dodecyltrimethylammonium Bromide (DTAB) has been carried out by conductance measurements in aqueous medium and in aqueous solution of K 2 SO 4 salt over temperature range of (303.15 to 318.15) K. For pure DTAB and drug-DTAB systems, three critical micelle concentrations were obtained. The third critical micelle concentration (c ∗ 3 ) indicates that the spherical micelle turns into rod shape that is sphere to rod transition. The c ∗ values of DTAB are changed due to the addition of cephalosporin drugs. In addition, the change of the values of c ∗ 1 , c ∗ 2 and c ∗ 3 with increase of the concentration of drugs indicate the presence of interaction between drug and DTAB. The c ∗ values indicate that micellization for the cephalosporins-surfactant systems in water follow the order: CFM-surfactant ∗ values for the cephalosporins - DTAB systems in aqueous K 2 SO 4 are lower in magnitude than those in pure water and the values decrease with increase of the concentrations of K 2 SO 4 at a particular temperature. A significant decrease of c ∗ values in the presence of K 2 SO 4 for cephalosporins-DTAB systems indicates that drug supported ionic micelle formation is much favoured in aqueous K 2 SO 4 solution compared to that in pure water. For cephalosporin-DTAB systems, ΔG 0 m values are negative which indicate that the drugs mediated ionic micelle formation processes are

  2. A at single nucleotide polymorphism-358 is required for G at -420 to confer the highest plasma resistin in the general Japanese population.

    Directory of Open Access Journals (Sweden)

    Hiroshi Onuma

    Full Text Available Insulin resistance is a feature of type 2 diabetes. Resistin, secreted from adipocytes, causes insulin resistance in mice. We previously reported that the G/G genotype of single nucleotide polymorphism (SNP at -420 (rs1862513 in the human resistin gene (RETN increased susceptibility to type 2 diabetes by enhancing its promoter activity. Plasma resistin was highest in Japanese subjects with G/G genotype, followed by C/G, and C/C. In this study, we cross-sectionally analyzed plasma resistin and SNPs in the RETN region in 2,019 community-dwelling Japanese subjects. Plasma resistin was associated with SNP-638 (rs34861192, SNP-537 (rs34124816, SNP-420, SNP-358 (rs3219175, SNP+299 (rs3745367, and SNP+1263 (rs3745369 (P<10(-13 in all cases. SNP-638, SNP -420, SNP-358, and SNP+157 were in the same linkage disequilibrium (LD block. SNP-358 and SNP-638 were nearly in complete LD (r(2 = 0.98, and were tightly correlated with SNP-420 (r(2 = 0.50, and 0.51, respectively. The correlation between either SNP-358 (or SNP-638 or SNP-420 and plasma resistin appeared to be strong (risk alleles for high plasma resistin; A at SNP-358, r(2 = 0.5224, P = 4.94x10(-324; G at SNP-420, r(2 = 0.2616, P = 1.71x10(-133. In haplotypes determined by SNP-420 and SNP-358, the estimated frequencies for C-G, G-A, and G-G were 0.6700, 0.2005, and 0.1284, respectively, and C-A was rare (0.0011, suggesting that subjects with A at -358, generally had G at -420. This G-A haplotype conferred the highest plasma resistin (8.24 ng/ml difference/allele compared to C-G, P<0.0001. In THP-1 cells, the RETN promoter with the G-A haplotype showed the highest activity. Nuclear proteins specifically recognized one base difference at SNP-358, but not at SNP-638. Therefore, A at -358 is required for G at -420 to confer the highest plasma resistin in the general Japanese population. In Caucasians, the association between SNP-420 and plasma resistin is not strong, and A at -358 may not exist

  3. The first cytogenetic description of Euleptes europaea (Gené, 1839 from Northern Sardinia reveals the highest diploid chromosome number among sphaerodactylid geckos (Sphaerodactylidae, Squamata

    Directory of Open Access Journals (Sweden)

    Ekaterina Gornung

    2013-06-01

    Full Text Available The karyotype of a sphaerodactylid gecko Euleptes europaea (Gené, 1839 was assembled for the first time in this species. It is made of 2n = 42 gradually decreasing in size chromosomes, the highest chromosome number so far acknowledged in the family Sphaerodactylidae. The second chromosome pair of the karyotype appears slightly heteromorphic in the male individual. Accordingly, FISH with a telomeric probe revealed an uneven distribution of telomeric repeats on the two homologues of this pair, which may be indicative of an XY sex-determination system in the species, to be further investigated.

  4. Target mediated drug disposition with drug-drug interaction, Part II: competitive and uncompetitive cases.

    Science.gov (United States)

    Koch, Gilbert; Jusko, William J; Schropp, Johannes

    2017-02-01

    We present competitive and uncompetitive drug-drug interaction (DDI) with target mediated drug disposition (TMDD) equations and investigate their pharmacokinetic DDI properties. For application of TMDD models, quasi-equilibrium (QE) or quasi-steady state (QSS) approximations are necessary to reduce the number of parameters. To realize those approximations of DDI TMDD models, we derive an ordinary differential equation (ODE) representation formulated in free concentration and free receptor variables. This ODE formulation can be straightforward implemented in typical PKPD software without solving any non-linear equation system arising from the QE or QSS approximation of the rapid binding assumptions. This manuscript is the second in a series to introduce and investigate DDI TMDD models and to apply the QE or QSS approximation.

  5. Isoflurane minimum alveolar concentration reduction by fentanyl.

    Science.gov (United States)

    McEwan, A I; Smith, C; Dyar, O; Goodman, D; Smith, L R; Glass, P S

    1993-05-01

    Isoflurane is commonly combined with fentanyl during anesthesia. Because of hysteresis between plasma and effect site, bolus administration of fentanyl does not accurately describe the interaction between these drugs. The purpose of this study was to determine the MAC reduction of isoflurane by fentanyl when both drugs had reached steady biophase concentrations. Seventy-seven patients were randomly allocated to receive either no fentanyl or fentanyl at several predetermined plasma concentrations. Fentanyl was administered using a computer-assisted continuous infusion device. Patients were also randomly allocated to receive a predetermined steady state end-tidal concentration of isoflurane. Blood samples for fentanyl concentration were taken at 10 min after initiation of the infusion and before and immediately after skin incision. A minimum of 20 min was allowed between the start of the fentanyl infusion and skin incision. The reduction in the MAC of isoflurane by the measured fentanyl concentration was calculated using a maximum likelihood solution to a logistic regression model. There was an initial steep reduction in the MAC of isoflurane by fentanyl, with 3 ng/ml resulting in a 63% MAC reduction. A ceiling effect was observed with 10 ng/ml providing only a further 19% reduction in MAC. A 50% decrease in MAC was produced by a fentanyl concentration of 1.67 ng/ml. Defining the MAC reduction of isoflurane by all the opioids allows their more rational administration with inhalational anesthetics and provides a comparison of their relative anesthetic potencies.

  6. Refractometry for quality control of anesthetic drug mixtures.

    Science.gov (United States)

    Stabenow, Jennifer M; Maske, Mindy L; Vogler, George A

    2006-07-01

    Injectable anesthetic drugs used in rodents are often mixed and further diluted to increase the convenience and accuracy of dosing. We evaluated clinical refractometry as a simple and rapid method of quality control and mixing error detection of rodent anesthetic or analgesic mixtures. Dilutions of ketamine, xylazine, acepromazine, and buprenorphine were prepared with reagent-grade water to produce at least 4 concentration levels. The refraction of each concentration then was measured with a clinical refractometer and plotted against the percentage of stock concentration. The resulting graphs were linear and could be used to determine the concentration of single-drug dilutions or to predict the refraction of drug mixtures. We conclude that refractometry can be used to assess the concentration of dilutions of single drugs and can verify the mixing accuracy of drug combinations when the components of the mixture are known and fall within the detection range of the instrument.

  7. Antimalarial drug quality in Africa.

    Science.gov (United States)

    Amin, A A; Kokwaro, G O

    2007-10-01

    continent have access to antimalarial drugs that are safe, of the highest quality standards and that retain their integrity throughout the distribution chain through adequate enforcement of existing legislation and enactment of new ones if necessary, and provision of the necessary resources for drug quality assurance.

  8. The Concentration of Nutrients in Tissues of Plantation-Grown Eastern Cottonwood (Populus deltoides Bart.)

    Science.gov (United States)

    M. G. Shelton; L. E. Nelson; G. L. Switzer; B. G. Blackmon

    1981-01-01

    Nutrient concentrations were determined for 10 tissues from each of 24 cottonwood trees that ranged in age from four to 16 years. Highest concentrations occurred in the most physiologically active tissues; i.e., stemtips, current branches and foliage. Tree age had little influence on the variation in nutrient concentration of tissues. Some differences in concentrations...

  9. A comparative study of vitamin E TPGS/HPMC supersaturated system and other solubilizer/polymer combinations to enhance the permeability of a poorly soluble drug through the skin.

    Science.gov (United States)

    Ghosh, Indrajit; Michniak-Kohn, Bozena

    2012-11-01

    In transdermal drug delivery systems (TDDS), it is a challenge to achieve stable and prolonged high permeation rates across skin, because the concentration of the drug dissolved in the matrix has to be high in order to maintain zero order release kinetics of the drug. In case of poorly soluble drugs, due to thermodynamic challenges, there is a high tendency for the drug to nucleate immediately after formulating or even during storage. The present study focuses on the efficiency of vitamin E TPGS/HPMC supersaturated solution and other solubilizer/polymer systems to improve the solubility of the drug and inhibit crystal growth in the transdermal formulation. Effect of several solubilizers, for example, Pluronic F-127, vitamin E TPGS and co-solvent, for example, propylene glycol (PG) were studied on the supersaturated systems of ibuprofen as model drug. Various stabilizers such as hydroxylpropyl methylcellulose (HPMC 3 cps) and polyvinylpyrrolidone (PVP K-30) were examined to evaluate their crystal inhibitory effects. Different analytical tools were used in this study to detect the growth of crystals in the systems. Vitamin E TPGS and HPMC 3 cps formulation produced the highest permeation rate of the drug as compared to other systems. In addition, the onset of crystallization time was shown to be longer with this formulation as compared to other solubilizer/polymer combinations.

  10. Ion-Responsive Drug Delivery Systems.

    Science.gov (United States)

    Yoshida, Takayuki; Shakushiro, Kohsuke; Sako, Kazuhiro

    2018-02-08

    Some kinds of cations and anions are contained in body fluids such as blood, interstitial fluid, gastrointestinal juice, and tears at relatively high concentration. Ionresponsive drug delivery is available to design the unique dosage formulations which provide optimized drug therapy with effective, safe and convenient dosing of drugs. The objective of the present review was to collect, summarize, and categorize recent research findings on ion-responsive drug delivery systems. Ions in body fluid/formulations caused structural changes of polymers/molecules contained in the formulations, allow formulations exhibit functions. The polymers/molecules responding to ions were ion-exchange resins/fibers, anionic or cationic polymers, polymers exhibiting transition at lower critical solution temperature, self-assemble supramolecular systems, peptides, and metalorganic frameworks. The functions of ion-responsive drug delivery systems were categorized to controlled drug release, site-specific drug release, in situ gelation, prolonged retention at the target sites, and enhancement of drug permeation. Administration of the formulations via oral, ophthalmic, transdermal, and nasal routes has showed significant advantages in the recent literatures. Many kinds of drug delivery systems responding to ions have been reported recently for several administration routes. Improvement and advancement of these systems can maximize drugs potential and contribute to patients in the world. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration.

    Directory of Open Access Journals (Sweden)

    Donghee Park

    Full Text Available Sonophoresis can increase skin permeability to various drugs in transdermal drug delivery. Cavitation is recognized as the predominant mechanism of sonophoresis. Recently, a new logical approach to enhance the efficiency of transdermal drug delivery was tried. It is to utilize the engineered microbubble and its resonant frequency for increase of cavitation activity. Actively-induced cavitation with low-intensity ultrasound (less than ~1 MPa causes disordering of the lipid bilayers and the formation of aqueous channels by stable cavitation which indicates a continuous oscillation of bubbles. Furthermore, the mutual interactions of microbubble determined by concentration of added bubble are also thought to be an important factor for activity of stable cavitation, even in different characteristics of drug. In the present study, we addressed the dependence of ultrasound contrast agent concentration using two types of drug on the efficiency of transdermal drug delivery. Two types of experiment were designed to quantitatively evaluate the efficiency of transdermal drug delivery according to ultrasound contrast agent concentration. First, an experiment of optical clearing using a tissue optical clearing agent was designed to assess the efficiency of sonophoresis with ultrasound contrast agents. Second, a Franz diffusion cell with ferulic acid was used to quantitatively determine the amount of drug delivered to the skin sample by sonophoresis with ultrasound contrast agents. The maximum enhancement ratio of sonophoresis with a concentration of 1:1,000 was approximately 3.1 times greater than that in the ultrasound group without ultrasound contrast agent and approximately 7.5 times greater than that in the control group. These results support our hypothesis that sonophoresis becomes more effective in transdermal drug delivery due to the presence of engineered bubbles, and that the efficiency of transdermal drug delivery using sonophoresis with

  12. Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration.

    Science.gov (United States)

    Park, Donghee; Song, Gillsoo; Jo, Yongjun; Won, Jongho; Son, Taeyoon; Cha, Ohrum; Kim, Jinho; Jung, Byungjo; Park, Hyunjin; Kim, Chul-Woo; Seo, Jongbum

    2016-01-01

    Sonophoresis can increase skin permeability to various drugs in transdermal drug delivery. Cavitation is recognized as the predominant mechanism of sonophoresis. Recently, a new logical approach to enhance the efficiency of transdermal drug delivery was tried. It is to utilize the engineered microbubble and its resonant frequency for increase of cavitation activity. Actively-induced cavitation with low-intensity ultrasound (less than ~1 MPa) causes disordering of the lipid bilayers and the formation of aqueous channels by stable cavitation which indicates a continuous oscillation of bubbles. Furthermore, the mutual interactions of microbubble determined by concentration of added bubble are also thought to be an important factor for activity of stable cavitation, even in different characteristics of drug. In the present study, we addressed the dependence of ultrasound contrast agent concentration using two types of drug on the efficiency of transdermal drug delivery. Two types of experiment were designed to quantitatively evaluate the efficiency of transdermal drug delivery according to ultrasound contrast agent concentration. First, an experiment of optical clearing using a tissue optical clearing agent was designed to assess the efficiency of sonophoresis with ultrasound contrast agents. Second, a Franz diffusion cell with ferulic acid was used to quantitatively determine the amount of drug delivered to the skin sample by sonophoresis with ultrasound contrast agents. The maximum enhancement ratio of sonophoresis with a concentration of 1:1,000 was approximately 3.1 times greater than that in the ultrasound group without ultrasound contrast agent and approximately 7.5 times greater than that in the control group. These results support our hypothesis that sonophoresis becomes more effective in transdermal drug delivery due to the presence of engineered bubbles, and that the efficiency of transdermal drug delivery using sonophoresis with microbubbles depends on the

  13. NSAIDs: can the presence of infectious agent influence the choice of analgesic drug?

    Directory of Open Access Journals (Sweden)

    О. А. Podpletnya

    2017-08-01

    Full Text Available Purpose. Considering the significant prevalence of comorbid pathology there is a high probability of NSAID use in patients with concomitant infection. In view of this screening of antimicrobial properties of their main groups was conducted for the purpose of selecting the most promising ones for further in-depth study. Materials and methods. The study of microorganisms’ sensitivity was conducted using standard research methods – the method of "wells" and by determining the antibacterial properties of drugs, using tablets, based on the ability of the drug to diffuse into agar, used for sowing the test-culture. As the test cultures S. aureus, S. mutans, S. pyogenes, P. aeruginosa, E. Coli, isolated from patients who were treated in hospital were used. Predominant blocker of COX-1 (acetylsalicylic acid, ASA, nonselective blockers of COX-1 and COX-2 (ketorolac, diclofenac sodium, ibuprofen, mefenamic acid, dexketoprofen, predominant blockers of COX-2 (meloxicam and nimesulide, selective blockers of COX-2 (celecoxib, selective blockers of COX-3 (COX-1 in the brain paracetamol and metamizole were tested. Results. The studies found that most of the tested NSAIDs have antimicrobial activity. Leader drugs in expressiveness of antimicrobial effects are drugs that have sufficient COX-1 (3 - activity: ASA, diclofenac, dexketoprofen, metamizole, and lesser extent – paracetamol. Tested NSAIDs showed the highest activity against gram-positive coccal flora, mostly affecting S. Pyogenes. Blockers of COX-3 paracetamol and metamizole, unlike other studied drugs, showed stronger antipseudomonal (both – moderate and antistaphylococcal action (metamizole. Conclusions. NSAIDs with antimicrobial activity can potentially increase the activity of antiinfectious therapy. At the same time, the antimicrobial activity of NSAIDs, theoretically, can promote microbial resistance because of existence of microorganisms in a medium with subthreshold concentrations of drugs

  14. Utility of coloured hair for the detection of drugs and alcohol.

    Science.gov (United States)

    Agius, Ronald

    2014-06-01

    The aim of this paper is to assess the utility of coloured hair for the detection of drugs and alcohol in a large statistically significant population. The positivity rate, the 1st, 5th, 50th, 95th, and 99th percentiles of five amphetamines, cannabinoids, cocaine, four opiates, methadone, buprenorphine, seven benzodiazepines, and ethyl glucuronide (EtG) in 9488 non-treated and 1026 cosmetically treated (dyed or bleached) authentic hair samples was compared. Analytical methods used were accredited for forensic purposes at the cut-offs defined by the German driving licence re-granting medical and psychological assessment (MPA) guidelines. Considering only the drug classes for which at least 10 positive samples were detected, the positivity rate in non-treated hair was highest for alcohol (4.50%; measured using EtG at concentrations ≥ 7 pg/mg hair), followed by THC (2.00%), cocaine (1.75%), and amphetamine (0.59%). While the 1st to 99th percentile range was significantly lower for drugs in treated, compared to non-treated hair, no significant change was observed for EtG. Additionally, no significant difference in the positivity rate was observed between treated hair and non-treated hair for both drugs and EtG. This study is the first attempt to evaluate the influence of cosmetic treatment, mainly dying, on the positivity rate for both drugs and EtG in hair samples submitted routinely for abstinence testing and the first to indicate that dyed and eventually bleached hair is not necessarily useless in detecting drugs and/or alcohol consumption, thus making coloured hair analysis still useful, often being the only possibility to prove such misuse. Copyright © 2014 John Wiley & Sons, Ltd.

  15. Predictors of in vitro fertilization outcomes in women with highest follicle-stimulating hormone levels ≥ 12 IU/L: a prospective cohort study.

    Directory of Open Access Journals (Sweden)

    Lina N Huang

    Full Text Available The purpose of this study is to evaluate factors predictive of outcomes in women with highest follicle-stimulating hormone (FSH levels ≥ 12 IU/L on basal testing, undergoing in vitro fertilization (IVF.A prospective cohort study was conducted at Stanford University Hospital in the Reproductive Endocrinology and Infertility Center for 12 months. Women age 21 to 43 undergoing IVF with highest FSH levels on baseline testing were included. Donor/Recipient and frozen embryo cycles were excluded from this study. Prognostic factors evaluated in association with clinical pregnancy rates were type of infertility diagnosis and IVF stimulation parameters.The current study found that factors associated with clinical pregnancy were: increased number of mature follicles on the day of triggering, number of oocytes retrieved, number of Metaphase II oocytes if intracytoplasmic sperm injection was done, and number of embryos developed 24 hours after retrieval.Our findings suggest that it would be beneficial for women with increased FSH levels to attempt a cycle of IVF. Results of ovarian stimulation, especially embryo quantity appear to be the best predictors of IVF outcomes and those can only be obtained from a cycle of IVF. Therefore, increased basal FSH levels should not discourage women from attempting a cycle of IVF.

  16. Evaluating the consistency of location of the most severe acute skin reaction and highest skin dose measured by thermoluminescent dosimeter during radiotherapy for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Li-Min, E-mail: limin.sun@yahoo.com [Department of Radiation Oncology, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung City, Taiwan (China); Huang, Chih-Jen [Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Faculty of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Chen, Hsiao-Yun [Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Chang, Gia-Hsin [Department of Radiation Oncology, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung City, Taiwan (China); Tsao, Min-Jen [Department of General Surgery, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung City, Taiwan (China)

    2016-10-01

    We conducted this prospective study to evaluate whether the location of the most severe acute skin reaction matches the highest skin dose measured by thermoluminescent dosimeter (TLD) during adjuvant radiotherapy (RT) for patients with breast cancer after breast conservative surgery. To determine whether TLD measurement can reflect the location of the most severe acute skin reaction, 80 consecutive patients were enrolled in this prospective study. We divided the irradiated field into breast, axillary, inframammary fold, and areola/nipple areas. In 1 treatment session when obvious skin reaction occurred, we placed the TLD chips onto the 4 areas and measured the skin dose. We determined whether the highest measured skin dose area is consistent with the location of the most severe skin reaction. The McNemar test revealed that the clinical skin reaction and TLD measurement are more consistent when the most severe skin reaction occurred at the axillary area, and the p = 0.0108. On the contrary, TLD measurement of skin dose is less likely consistent with clinical observation when the most severe skin reaction occurred at the inframammary fold, breast, and areola/nipple areas (all the p > 0.05). Considering the common site of severe skin reaction over the axillary area, TLD measurement may be an appropriate way to predict skin reaction during RT.

  17. On the Derivation of Highest-Order Compact Finite Difference Schemes for the One- and Two-Dimensional Poisson Equation with Dirichlet Boundary Conditions

    KAUST Repository

    Settle, Sean O.

    2013-01-01

    The primary aim of this paper is to answer the question, What are the highest-order five- or nine-point compact finite difference schemes? To answer this question, we present several simple derivations of finite difference schemes for the one- and two-dimensional Poisson equation on uniform, quasi-uniform, and nonuniform face-to-face hyperrectangular grids and directly prove the existence or nonexistence of their highest-order local accuracies. Our derivations are unique in that we do not make any initial assumptions on stencil symmetries or weights. For the one-dimensional problem, the derivation using the three-point stencil on both uniform and nonuniform grids yields a scheme with arbitrarily high-order local accuracy. However, for the two-dimensional problem, the derivation using the corresponding five-point stencil on uniform and quasi-uniform grids yields a scheme with at most second-order local accuracy, and on nonuniform grids yields at most first-order local accuracy. When expanding the five-point stencil to the nine-point stencil, the derivation using the nine-point stencil on uniform grids yields at most sixth-order local accuracy, but on quasi- and nonuniform grids yields at most fourth- and third-order local accuracy, respectively. © 2013 Society for Industrial and Applied Mathematics.

  18. Neonates need tailored drug formulations.

    Science.gov (United States)

    Allegaert, Karel

    2013-02-08

    Drugs are very strong tools used to improve outcome in neonates. Despite this fact and in contrast to tailored perfusion equipment, incubators or ventilators for neonates, we still commonly use drug formulations initially developed for adults. We would like to make the point that drug formulations given to neonates need to be tailored for this age group. Besides the obvious need to search for active compounds that take the pathophysiology of the newborn into account, this includes the dosage and formulation. The dosage or concentration should facilitate the administration of low amounts and be flexible since clearance is lower in neonates with additional extensive between-individual variability. Formulations need to be tailored for dosage variability in the low ranges and also to the clinical characteristics of neonates. A specific focus of interest during neonatal drug development therefore is a need to quantify and limit excipient exposure based on the available knowledge of their safety or toxicity. Until such tailored vials and formulations become available, compounding practices for drug formulations in neonates should be evaluated to guarantee the correct dosing, product stability and safety.

  19. Metals in the Scheldt estuary: From environmental concentrations to bioaccumulation

    International Nuclear Information System (INIS)

    Van Ael, Evy; Blust, Ronny; Bervoets, Lieven

    2017-01-01

    To investigate the relationship between metal concentrations in abiotic compartments and in aquatic species, sediment, suspended matter and several aquatic species (Polychaeta, Oligochaeta, four crustacean species, three mollusc species and eight fish species) were collected during three seasons at six locations along the Scheldt estuary (the Netherlands-Belgium) and analysed on their metal content (Ag, Cd, Co, Cr, Cu, Ni, Pb, Zn and the metalloid As). Sediment and biota tissue concentrations were significantly influenced by sampling location, but not by season. Measurements of Acid Volatile Sulphides (AVS) concentrations in relation to Simultaneously Extracted Metals (SEM) in the sediment suggested that not all metals in the sediment will be bound to sulphides and some metals might be bioavailable. For all metals but zinc, highest concentrations were measured in invertebrate species; Ag and Ni in periwinkle, Cr, Co and Pb in Oligochaete worms and As, Cd and Cu in crabs and shrimp. Highest concentrations of Zn were measured in the kidney of European smelt. In fish, for most of the metals, the concentrations were highest in liver or kidney and lowest in muscle. For Zn however, highest concentrations were measured in the kidney of European smelt. For less than half of the metals significant correlations between sediment metal concentrations and bioaccumulated concentrations were found (liver/hepatopancreas or whole organism). To calculate the possible human health risk by consumption, average and maximum metal concentrations in the muscle tissues were compared to the minimum risk levels (MRLs). Concentrations of As led to the highest risk potential for all consumable species. Cadmium and Cu posed only a risk when consuming the highest contaminated shrimp and shore crabs. Consuming blue mussel could result in a risk for the metals As, Cd and Cr. - Highlights: • This is the first study investigating metal distribution along the aquatic ecosystem of the Scheldt

  20. Cytotoxic Drugs Departments as a precondition for high-quality product

    Directory of Open Access Journals (Sweden)

    Katarzyna Głuszek

    2014-06-01

    Full Text Available Cancer control is a tremendous challenge not only for the ill patient and physicians, but also for the whole health care system. For the first time, during the European Conference of Oncology Pharmacists, the highest standards of pharmaceutical care were proposed for cancer patients. Undoubtedly, the lifestyle and prophylaxis which would enable the detection of cancer at an early stage exert an effect on the development of the disease. Cytostatics show toxic, mutagenic, oncogenic and immunosuppressive effects; therefore, their preparation should be handled by the Central Cytotoxic Drugs Department, because the majority of the drugs prepared belong to Register A. Drugs are manufactured in accordance with GMP principles. All-Polish Standards adopted by the Polish Pharmaceutical Association delineate the direction to be developed by every hospital with respect to its own procedures and instructions. The Master of Pharmacy is responsible for the preparation of cytotoxic drugs. At one bench should work an operator and an assistant. The recommended working time should not exceed 2 h without break, and 5 h daily. The person who collects cytotoxic drugs from the Central Department should use a legible sign and a stamp including the hour and date of collection. While manufacturing cytostatics for patients in daily doses it is recommended to use concentrates in the form of solutions rather than lyophilised powders, which results in the shortening of the stage of production of the drug and reduces the possibility of forming aerosols; in the case of closed infusion systems (containers for infusion liquids which are used for the production of daily doses, the cabinet should be equipped in two tight docks for dispensing. Needleless connection of the LUER-LOCK type – a recommendation of the ISOPP – guarantees a tight connection with the drug transfer port even in the case of an increase in pressure during the manufacture of drugs. To a certain extent