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Sample records for significantly higher potency

  1. Competitive Intelligence: Significance in Higher Education

    Science.gov (United States)

    Barrett, Susan E.

    2010-01-01

    Historically noncompetitive, the higher education sector is now having to adjust dramatically to new and increasing demands on numerous levels. To remain successfully operational within the higher educational market universities today must consider all relevant forces which can impact present and future planning. Those institutions that were…

  2. Towards an improved prediction of the free radical scavenging potency of flavonoids: the significance of double PCET mechanisms.

    Science.gov (United States)

    Amić, Ana; Marković, Zoran; Dimitrić Marković, Jasmina M; Stepanić, Višnja; Lučić, Bono; Amić, Dragan

    2014-01-01

    The 1H(+)/1e(-) and 2H(+)/2e(-) proton-coupled electron transfer (PCET) processes of free radical scavenging by flavonoids were theoretically studied for aqueous and lipid environments using the PM6 and PM7 methods. The results reported here indicate that the significant contribution of the second PCET mechanism, resulting in the formation of a quinone/quinone methide, effectively discriminates the active from inactive flavonoids. The predictive potency of descriptors related to the energetics of second PCET mechanisms (the second O-H bond dissociation enthalpy (BDE2) related to hydrogen atom transfer (HAT) mechanism, and the second electron transfer enthalpy (ETE2) related to sequential proton loss electron transfer (SPLET) mechanism) are superior to the currently used indices, which are related to the first 1H(+)/1e(-) processes, and could serve as primary descriptors in development of the QSAR (quantitative structure-activity relationships) of flavonoids. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Comparison of the interleukin-1β-inducing potency of allergenic spores from higher fungi (Basidiomycetes) in a cryopreserved human whole blood system

    Science.gov (United States)

    Rivera-Mariani, Félix E.; Vysyaraju, Kranthi; Negherbon, Jesse; Levetin, Estelle; Horner, W. Elliot; Hartung, Thomas; Breysse, Patrick N.

    2014-01-01

    Background Spores from basidiomycete fungi (basidiospores) are highly prevalent in the atmosphere of urban and rural settings. Studies have confirmed their potential to affect human health as allergens. Less is known about their potential to serve as stimuli of the innate immune system and induce pro-inflammatory reactions. Methods In this study, we evaluated the pro-inflammatory potential of spores from 11 allergenic gilled (Pleurotus ostreatus, Oudemansiella radicata, Armillaria tabescens, Coprinus micaceus, Pluteus cervinus, Chlorophyllum molybdites) and non-gilled (Pisolithus arhizus, Merulius tremullosus, Calvatia cyathiformis, Lycoperdon pyriforme, Boletus bicolor) basidiomycetes fungi based on their potency to induce the release of the pro-inflammatory cytokine interleukin (IL)-1β in a cryopreserved human whole blood system. In addition, the role of morphological features of the spores (surface area, shape, and pigmentation) were examined for their role in the spores’ interleukin (IL)-1β-including potency. Peripheral blood from healthy volunteers was collected, pooled, and cryopreserved. After stimulating the cryopreserved pooled blood with 106 to 103 basidiospores/ml, the concentration of IL-1β in culture supernatants was determined with ELISA. Results Basidiospores manifested concentration-dependent IL-1β-inducing potency, which was more noteworthy among basidiospores from gilled basidiomycetes. At higher concentrations of basidiospores, the IL-1β-inducing potency was able to be differentiated in the cryopreserved human whole blood system. Morphological features did not correlate with the IL-1β-inducing potency of the basidiospores, suggesting that non-morphological properties modulate the IL-1β-inducing potency. Conclusion Our data provides evidence of the pro-inflammatory potential of basidiospores, and the utility of cryopreserved human whole blood as a human-based in-vitro system to study the immune reactivity of allergenic basidiospores. PMID

  4. Potency backprojection

    Science.gov (United States)

    Okuwaki, R.; Kasahara, A.; Yagi, Y.

    2017-12-01

    The backprojection (BP) method has been one of the powerful tools of tracking seismic-wave sources of the large/mega earthquakes. The BP method projects waveforms onto a possible source point by stacking them with the theoretical-travel-time shifts between the source point and the stations. Following the BP method, the hybrid backprojection (HBP) method was developed to enhance depth-resolution of projected images and mitigate the dummy imaging of the depth phases, which are shortcomings of the BP method, by stacking cross-correlation functions of the observed waveforms and theoretically calculated Green's functions (GFs). The signal-intensity of the BP/HBP image at a source point is related to how much of observed waveforms was radiated from that point. Since the amplitude of the GF associated with the slip-rate increases with depth as the rigidity increases with depth, the intensity of the BP/HBP image inherently has depth dependence. To make a direct comparison of the BP/HBP image with the corresponding slip distribution inferred from a waveform inversion, and discuss the rupture properties along the fault drawn from the waveforms in high- and low-frequencies with the BP/HBP methods and the waveform inversion, respectively, it is desirable to have the variants of BP/HBP methods that directly image the potency-rate-density distribution. Here we propose new formulations of the BP/HBP methods, which image the distribution of the potency-rate density by introducing alternative normalizing factors in the conventional formulations. For the BP method, the observed waveform is normalized with the maximum amplitude of P-phase of the corresponding GF. For the HBP method, we normalize the cross-correlation function with the squared-sum of the GF. The normalized waveforms or the cross-correlation functions are then stacked for all the stations to enhance the signal to noise ratio. We will present performance-tests of the new formulations by using synthetic waveforms and the

  5. Progestin and estrogen potency of combination oral contraceptives and endometrial cancer risk.

    Science.gov (United States)

    Maxwell, G L; Schildkraut, J M; Calingaert, B; Risinger, J I; Dainty, L; Marchbanks, P A; Berchuck, A; Barrett, J C; Rodriguez, G C

    2006-11-01

    Using data from a case-control study of endometrial cancer, we investigated the relationship between the progestin and estrogen potency in combination oral contraceptives (OCs) and the risk of developing endometrial cancer. Subjects included 434 endometrial cancer cases and 2,557 controls identified from the Cancer and Steroid Hormone (CASH) study. OCs were classified into four categories according to the individual potencies of each hormonal constituent (high versus low estrogen or progestin potency). Logistic regression was used to evaluate associations between endometrial cancer risk and combination OC formulations. With non-users as the referent group, use of OCs with either high potency progestin [odds ratio for endometrial cancer (OR)=0.21, 95% confidence interval (CI)=0.10 to 0.43] or with low potency progestin (OR=0.39, 95% CI=0.25 to 0.60) were both associated with a decreased risk of endometrial cancer. Overall high progestin potency OCs did not confer significantly more protection than low progestin potency OCs (OR=0.52, 95% CI=0.24 to 1.14). However, among women with a body mass index of 22.1 kg/m2 or higher, those who used high progestin potency oral contraceptives had a lower risk of endometrial cancer than those who used low progestin potency oral contraceptives (OR=0.31, 95% CI=0.11 to 0.92) while those with a BMI below 22.1 kg/m2 did not (OR=1.36, 95% CI=0.39 to 4.70). The potency of the progestin in most OCs appears adequate to provide a protective effect against endometrial cancer. Higher progestin-potency OCs may be more protective than lower progestin potency OCs among women with a larger body habitus.

  6. The Effects of Medical Marijuana Laws on Potency

    Science.gov (United States)

    Pacula, Rosalie Liccardo; Heaton, Paul

    2014-01-01

    Background Marijuana potency has risen dramatically over the past two decades. In the United States, it is unclear whether state medical marijuana policies have contributed to this increase. Methods Employing a differences-in-differences model within a mediation framework, we analyzed data on n = 39,157 marijuana samples seized by law enforcement in 51 U.S. jurisdictions between 1990-2010, producing estimates of the direct and indirect effects of state medical marijuana laws on potency, as measured by Δ9-tetrahydrocannabinol content. Results We found evidence that potency increased by a half percentage point on average after legalization of medical marijuana, although this result was not significant. When we examined specific medical marijuana supply provisions, results suggest that legal allowances for retail dispensaries had the strongest influence, significantly increasing potency by about one percentage point on average. Our mediation analyses examining the mechanisms through which medical marijuana laws influence potency found no evidence of direct regulatory impact. Rather, the results suggest that the impact of these laws occurs predominantly through a compositional shift in the share of the market captured by high-potency sinsemilla. Conclusion Our findings have important implications for policymakers and those in the scientific community trying to understand the extent to which greater availability of higher potency marijuana increases the risk of negative public health outcomes, such as drugged driving and drug-induced psychoses. Future work should reconsider the impact of medical marijuana laws on health outcomes in light of dramatic and ongoing shifts in both marijuana potency and the medical marijuana policy environment. PMID:24502887

  7. Synthetic risks, risk potency, and carcinogen regulation.

    Science.gov (United States)

    Viscusi, W K; Hakes, J K

    1998-01-01

    This article analyzes a comprehensive sample of over 350 chemicals tested for carcinogenicity to assess the determinants of the probability of regulation. Controlling for differences in the risk potency and noncancer risks, synthetic chemicals have a significantly higher probability of regulation overall: this is due to the greater likelihood of U.S. Food and Drug Administration (FDA) regulation. Measures of risk potency increase the probability of regulation by the U.S. Environmental Protection Agency (EPA), have a somewhat weaker positive effect on regulation by the U.S. Occupational Safety and Health Administration (OSHA), and decrease the likelihood of regulation by the FDA. The overall regulatory pattern is one in which the FDA targets synthetic chemicals and chemicals that pose relatively minor cancer risk. The EPA particularly performed more sensibly than many critics have suggested.

  8. Potency of Stem Cells

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Potency of Stem Cells. Totipotent Stem Cells (Zygote + first 2 divisions). -Can form placenta, embryo, and any cell of the body. Pluripotent (Embryonic Stem Cells). -Can form any cell of the body but can not form placenta, hence no embryo. Multipotent (Adult stem cells).

  9. Potency probability following conformal megavoltage radiotherapy using conventional doses for localized prostate cancer

    International Nuclear Information System (INIS)

    Mantz, C.A.; Song, P.; Farhangi, E.; Nautiyal, J.; Awan, A.; Ignacio, L.; Weichselbaum, R.; Vijayakumar, S.

    1997-01-01

    test, p = 0.741) between ages 50 and 65. Finally, potency probability after follow-up of 1 year or more in EBRT-treated patients was stratified by age and substratified by clinical stage and then compared to similarly stratified potencies for patients treated with NSRP. The prostatectomy data were derived from the pooled data of six large (total n, 952), independent series conducted at academic centers. For patients older than 70 years, 79.1% of EBRT patients and 32.9% of NSRP patients remained potent after treatment. For patients with stage B2 disease, 75.0% of EBRT patients and 49.3% of NSRP patients remained potent after treatment. Overall EBRT patient potency was 76.1% vs. 66.2% for NSRP patients. Conclusions: 1) By 36 months after completion of EBRT for localized prostate cancer, fully one-third of all patients becomes impotent; however, for patients younger than 70 years, the probability of impotence does not depart significantly from that for normal males. 2) In the EBRT-treated population, pre-EBRT partial potency, vascular disease, and diabetes are the most significant predispositions to the development of impotence. Patients with these predispositions, though, do not become impotent significantly earlier than other patients. 3) When comparing age and stage-stratified potency rates for EBRT and NSRP patients, potency is roughly equal for both modalities for most age and stage groups; however, for patients older than 70 years or with stage B2 disease, EBRT offers notably higher posttreatment potency rates than NSRP. Thus, for the treatment of localized prostate cancer, EBRT may not affect the normal age trend of impotence in younger patients and may induce impotence less frequently than NSRP in older patients or in patients with later stage disease

  10. Significantly higher Carabid beetle (Coleoptera: Carabidae) catch in conventionally than in organically managed Christmas tree plantations

    DEFF Research Database (Denmark)

    Bagge, Søren; Lund, Malthe; Rønn, Regin

    2012-01-01

    Carabid beetles play an important role as consumers of pest organisms in forestry and agriculture. Application of pesticides may negatively affect abundance and activity of carabid beetles, thus reducing their potential beneficial effect. We investigated how abundance and diversity of pitfall...... trapped carabid beetles (Coleoptera, Carabidae) varied between conventionally and organically managed Caucasian Fir (Abies nordmanniana (Stev.)) plantations, in northern Zealand, Denmark. We recorded significantly higher numbers of carabid beetle specimens and species at conventionally than at organically...

  11. The prevalence of coeliac disease is significantly higher in children compared with adults.

    Science.gov (United States)

    Mariné, M; Farre, C; Alsina, M; Vilar, P; Cortijo, M; Salas, A; Fernández-Bañares, F; Rosinach, M; Santaolalla, R; Loras, C; Marquès, T; Cusí, V; Hernández, M I; Carrasco, A; Ribes, J; Viver, J M; Esteve, M

    2011-02-01

    Some limited studies of coeliac disease have shown higher frequency of coeliac disease in infancy and adolescence than in adulthood. This finding has remained unnoticed and not adequately demonstrated. To assess whether there are age and gender differences in coeliac disease prevalence. A total of 4230 subjects were included consecutively (1 to ≥80 years old) reproducing the reference population by age and gender. Sample size was calculated assuming a population-based coeliac disease prevalence of 1:250. After an interim analysis, the paediatric sample was expanded (2010 children) due to high prevalence in this group. Anti-transglutaminase and antiendomysial antibodies were determined and duodenal biopsy was performed if positive. Log-linear models were fitted to coeliac disease prevalence by age allowing calculation of percentage change of prevalence. Differences between groups were compared using Chi-squared test. Twenty-one subjects had coeliac disease (male/female 1:2.5). Coeliac disease prevalence in the total population was 1:204. Coeliac disease prevalence was higher in children (1:71) than in adults (1:357) (P = 0.00005). A significant decrease of prevalence in older generations was observed [change of prevalence by age of -5% (95% CI: -7.58 to -2.42%)]. In the paediatric expanded group (1-14 years), a decrease of coeliac disease prevalence was also observed [prevalence change: -17% (95% CI: -25.02 to -6.10)]. The prevalence of coeliac disease in childhood was five times higher than in adults. Whether this difference is due to environmental factors influencing infancy, or latency of coeliac disease in adulthood, remains to be demonstrated in prospective longitudinal studies. © 2010 Blackwell Publishing Ltd.

  12. Quantitative structure - mesothelioma potency model ...

    Science.gov (United States)

    Cancer potencies of mineral and synthetic elongated particle (EP) mixtures, including asbestos fibers, are influenced by changes in fiber dose composition, bioavailability, and biodurability in combination with relevant cytotoxic dose-response relationships. A unique and comprehensive rat intra-pleural (IP) dose characterization data set with a wide variety of EP size, shape, crystallographic, chemical, and bio-durability properties facilitated extensive statistical analyses of 50 rat IP exposure test results for evaluation of alternative dose pleural mesothelioma response models. Utilizing logistic regression, maximum likelihood evaluations of thousands of alternative dose metrics based on hundreds of individual EP dimensional variations within each test sample, four major findings emerged: (1) data for simulations of short-term EP dose changes in vivo (mild acid leaching) provide superior predictions of tumor incidence compared to non-acid leached data; (2) sum of the EP surface areas (ÓSA) from these mildly acid-leached samples provides the optimum holistic dose response model; (3) progressive removal of dose associated with very short and/or thin EPs significantly degrades resultant ÓEP or ÓSA dose-based predictive model fits, as judged by Akaike’s Information Criterion (AIC); and (4) alternative, biologically plausible model adjustments provide evidence for reduced potency of EPs with length/width (aspect) ratios 80 µm. Regar

  13. External Stakeholders of Higher Education Institutions in Poland: Their Identification and Significance

    Science.gov (United States)

    Piotrowska-Piatek, Agnieszka

    2017-01-01

    In the context of the ongoing changes in the management systems of higher education, the issue of higher education institutions' (HEIs) relationships with external stakeholders are of key importance. This article discusses this problem from the perspective of Polish higher education system. The aim of it is to answer the following questions: (1)…

  14. Significant enhancement in thermoelectric performance of nanostructured higher manganese silicides synthesized employing a melt spinning technique.

    Science.gov (United States)

    Muthiah, Saravanan; Singh, R C; Pathak, B D; Avasthi, Piyush Kumar; Kumar, Rishikesh; Kumar, Anil; Srivastava, A K; Dhar, Ajay

    2018-01-25

    The limited thermoelectric performance of p-type Higher Manganese Silicides (HMS) in terms of their low figure-of-merit (ZT), which is far below unity, is the main bottle-neck for realising an efficient HMS based thermoelectric generator, which has been recognized as the most promising material for harnessing waste-heat in the mid-temperature range, owing to its thermal stability, earth-abundant and environmentally friendly nature of its constituent elements. We report a significant enhancement in the thermoelectric performance of nanostructured HMS synthesized using rapid solidification by optimizing the cooling rates during melt-spinning followed by spark plasma sintering of the resulting melt-spun ribbons. By employing this experimental strategy, an unprecedented ZT ∼ 0.82 at 800 K was realized in spark plasma sintered 5 at% Al-doped MnSi 1.73 HMS, melt spun at an optimized high cooling rate of ∼2 × 10 7 K s -1 . This enhancement in ZT represents a ∼25% increase over the best reported values thus far for HMS and primarily originates from a nano-crystalline microstructure consisting of a HMS matrix (20-40 nm) with excess Si (3-9 nm) uniformly distributed in it. This nanostructure, resulting from the high cooling rates employed during the melt-spinning of HMS, introduces a high density of nano-crystallite boundaries in a wide spectrum of nano-scale dimensions, which scatter the low-to-mid-wavelength heat-carrying phonons. This abundant phonon scattering results in a significantly reduced thermal conductivity of ∼1.5 W m -1 K -1 at 800 K, which primarily contributes to the enhancement in ZT.

  15. ASSESSING SELF-STUDY WORK’S SIGNIFICANT SKILLS FOR SUCCESSFUL LEARNING IN THE HIGHER SCHOOL

    Directory of Open Access Journals (Sweden)

    Galina V. Milovanova

    2017-06-01

    Full Text Available Introduction: the problem of organizing students’ independent work/self-study is not new, but the changes in the higher school for the last two decades show that the experience accumulated in the traditional educational model can be applied only when it is processed in the present-day conditions. The article analyses the innovative component of the educational process in terms of a significant increase in the volume of compulsory independent work in the university. Particular attention is paid to determining the levels of the formation of skills for independent work in terms of students’ readiness for its implementa¬tion. The aim of the research is to identify the most significant skills of independent work for successful study at the university. Materials and Methods: the research is based on general scholarly methods: analysis, comparison, generalisation. A questionnaire survey was carried out and a correlation analysis of the results was presented. The mathematical statistics methods in Excel application were u sed for processing the survey data. Results: the article focused on the relevance of formation the students’ ability to work independently in the learning process. Requirements for professionals recognize the need for knowledge and skills, but more importantly, the ability and readiness to complete this knowledge and be in a state of continuous education and self-education. In turn, readiness to self-education cannot exist without independent work. The ratio of students to work independently and their skills’ levels in this area of the gnostic, design, structural, organisational and communicative blocks were identified because o f the research. Discussion and Conclusions: the levels of the formation of the skills for independent work influence on the success of the learning. There is a correlation between indicators of achievement and the ability to work independently. Organisation and communication skills have significant

  16. Mediating Potency and Fear

    DEFF Research Database (Denmark)

    Christiansen, Steen Ledet

    2018-01-01

    Action movies participate in the administration of fear [Virilio, P., 2012. The administration of fear. Translated by Ames Hodges. Los Angeles, CA: Semiotext(e)], and the networked affects of contemporary warfare [Anderson, B., 2013. Targeting affective life from above: morale and airpower. In: P......’ [Shaviro, S., 2010. Post-cinematic affect. Winchester: Zero Books]. These intensity effects mediate between the age of terror's ecology of fear [Massumi, Brian, 2002. Parables for the virtual: movement, affect, sensation. Durham: Duke University Press] and our bodies. Rather than producing fear, action...... movies work to dispel fear by producing potency and bolstering resolve. We can thus understand action movies as participating in the biopolitical effects of contemporary warfare. Affect is globalized and intensified through action movies’ aesthetics, with the aim of producing a kind of drone subject...

  17. The Significance of Blackstone's Understanding of Sovereign Immunity for America's Public Institutions of Higher Education.

    Science.gov (United States)

    Snow, Brian A.; Thro, William E.

    2001-01-01

    Asserts that from the perspective of America's public institutions of higher education, Blackstone's greatest legacy is his understanding of sovereign immunity. Explores the similarities between Blackstone's understanding of sovereign immunity and the current jurisprudence of the U.S. Supreme Court. (EV)

  18. The risk of being depressed is significantly higher in cancer patients than in the general population

    DEFF Research Database (Denmark)

    Hartung, T J; Brähler, E; Faller, H

    2017-01-01

    BACKGROUND: Depression is a common co-morbidity of cancer that has a detrimental effect on quality of life, treatment adherence and potentially survival. We conducted an epidemiological multi-center study including a population-based random comparison sample and estimated the prevalence...... of depressive symptoms by cancer site, thereby identifying cancer patients with the highest prevalence of depression. PATIENTS AND METHODS: We included 4020 adult cancer inpatients and outpatients from five distinct regions across Germany in a proportional stratified random sample based on the nationwide cancer......% participated (51% women, mean age = 58 years). We estimated that one in four cancer patients (24%) is depressed (PHQ-9 ≥ 10). The odds of being depressed among cancer patients were more than five times higher than in the general population (OR, 5.4; 95% CI, 4.6-6.2). Patients with pancreatic (M = 8.0, SD = 5...

  19. Solar cells from 120 PPMA carbon-contaminated feedstock without significantly higher reverse current or shunt

    Energy Technology Data Exchange (ETDEWEB)

    Manshanden, P.; Coletti, G. [ECN Solar Energy, Petten (Netherlands)

    2012-09-15

    In a bid to drive down the cost of silicon wafers, several options for solar grade silicon feedstock have been investigated over the years. All methods have in common that the resulting silicon contains higher levels of impurities like dopants, oxygen, carbon or transition metals, the type and level of impurities depending on the raw materials and refining processes. In this work wafers from a p-type mc-Si ingot made with feedstock contaminated with 120 ppma of carbon have been processed into solar cells together with reference uncontaminated feedstock from semiconductor grade polysilicon with <0.4 ppma carbon. The results show that comparable reverse current, shunts, and efficiencies can be reached for both types of wafers. Gettering and defect hydrogenation effectiveness also did not deviate from the reference. Electroluminescence pictures do not show increased hotspot formation, even at -16V.

  20. Spatially resolved flux measurements of NOx from London suggest significantly higher emissions than predicted by inventories.

    Science.gov (United States)

    Vaughan, Adam R; Lee, James D; Misztal, Pawel K; Metzger, Stefan; Shaw, Marvin D; Lewis, Alastair C; Purvis, Ruth M; Carslaw, David C; Goldstein, Allen H; Hewitt, C Nicholas; Davison, Brian; Beevers, Sean D; Karl, Thomas G

    2016-07-18

    To date, direct validation of city-wide emissions inventories for air pollutants has been difficult or impossible. However, recent technological innovations now allow direct measurement of pollutant fluxes from cities, for comparison with emissions inventories, which are themselves commonly used for prediction of current and future air quality and to help guide abatement strategies. Fluxes of NOx were measured using the eddy-covariance technique from an aircraft flying at low altitude over London. The highest fluxes were observed over central London, with lower fluxes measured in suburban areas. A footprint model was used to estimate the spatial area from which the measured emissions occurred. This allowed comparison of the flux measurements to the UK's National Atmospheric Emissions Inventory (NAEI) for NOx, with scaling factors used to account for the actual time of day, day of week and month of year of the measurement. The comparison suggests significant underestimation of NOx emissions in London by the NAEI, mainly due to its under-representation of real world road traffic emissions. A comparison was also carried out with an enhanced version of the inventory using real world driving emission factors and road measurement data taken from the London Atmospheric Emissions Inventory (LAEI). The measurement to inventory agreement was substantially improved using the enhanced version, showing the importance of fully accounting for road traffic, which is the dominant NOx emission source in London. In central London there was still an underestimation by the inventory of 30-40% compared with flux measurements, suggesting significant improvements are still required in the NOx emissions inventory.

  1. Estrogenic and esterase-inhibiting potency in rainwater in relation to pesticide concentrations, sampling season and location

    International Nuclear Information System (INIS)

    Hamers, T.; Brink, P.J. van den; Mos, L.; Linden, S.C. van der; Legler, J.; Koeman, J.H.; Murk, A.J.

    2003-01-01

    Estrogenic potency of rainwater correlated well with organochlorine concentrations, but could not be attributed to specific pesticides. - In a year-round monitoring program (1998), pesticide composition and toxic potency of the mix of pollutants present in rainwater were measured. The goal of the study was to relate atmospheric deposition of toxic potency and pesticide composition to each other and to sampling period and local agricultural activity. Rainwater was collected in 26 consecutive periods of 14 days in a background location (BACK) and in two locations representative for different agricultural practices, i.e. intensive greenhouse horticulture (HORT) and flower bulb culture (BULB). Samples were chemically analyzed for carbamate (CARB), organophosphate (OP) and organochlorine (OC) pesticides and metabolites. Esterase inhibiting potency of rainwater extracts was measured in a specially developed bio-assay with honeybee esterases and was expressed as an equivalent concentration of the model inhibitor dichlorvos. Estrogenic potency of the extracts was measured in the ER-CALUX reporter gene assay and was expressed as an equivalent concentration of estradiol. Multivariate principal component analysis (PCA) techniques proved to be valuable tools to analyze the numerous pesticide concentrations in relation to toxic potency, sampling location, and sampling season. Pesticide composition in rainwater depended much more on sampling season than on sampling location, but differences between SPRING and SUMMER were mainly attributed to local differences in agricultural practice. On average, the esterase inhibiting potency exceeded the maximum permissible concentration set for dichlorvos in The Netherlands, and was significantly higher in HORT than in BACK and BULB. Esterase inhibition correlated significantly with OP and CARB concentrations, as expected given the working mechanism of these insecticides. The estrogenic potency incidentally exceeded NOEC levels reported for

  2. Estrogenic and esterase-inhibiting potency in rainwater in relation to pesticide concentrations, sampling season and location

    Energy Technology Data Exchange (ETDEWEB)

    Hamers, T.; Brink, P.J. van den; Mos, L.; Linden, S.C. van der; Legler, J.; Koeman, J.H.; Murk, A.J

    2003-05-01

    Estrogenic potency of rainwater correlated well with organochlorine concentrations, but could not be attributed to specific pesticides. - In a year-round monitoring program (1998), pesticide composition and toxic potency of the mix of pollutants present in rainwater were measured. The goal of the study was to relate atmospheric deposition of toxic potency and pesticide composition to each other and to sampling period and local agricultural activity. Rainwater was collected in 26 consecutive periods of 14 days in a background location (BACK) and in two locations representative for different agricultural practices, i.e. intensive greenhouse horticulture (HORT) and flower bulb culture (BULB). Samples were chemically analyzed for carbamate (CARB), organophosphate (OP) and organochlorine (OC) pesticides and metabolites. Esterase inhibiting potency of rainwater extracts was measured in a specially developed bio-assay with honeybee esterases and was expressed as an equivalent concentration of the model inhibitor dichlorvos. Estrogenic potency of the extracts was measured in the ER-CALUX reporter gene assay and was expressed as an equivalent concentration of estradiol. Multivariate principal component analysis (PCA) techniques proved to be valuable tools to analyze the numerous pesticide concentrations in relation to toxic potency, sampling location, and sampling season. Pesticide composition in rainwater depended much more on sampling season than on sampling location, but differences between SPRING and SUMMER were mainly attributed to local differences in agricultural practice. On average, the esterase inhibiting potency exceeded the maximum permissible concentration set for dichlorvos in The Netherlands, and was significantly higher in HORT than in BACK and BULB. Esterase inhibition correlated significantly with OP and CARB concentrations, as expected given the working mechanism of these insecticides. The estrogenic potency incidentally exceeded NOEC levels reported for

  3. Comparative potency of formulations of mometasone furoate in terms of inhibition of ′PIRHR′ in the forearm skin of normal human subjects measured with laser doppler velocimetry

    Directory of Open Access Journals (Sweden)

    Kulhalli Prabhakar

    2005-01-01

    Full Text Available BACKGROUND AND AIMS: Topical glucocorticoid formulations are widely used for effective treatment and control of a variety of dermatoses. Mometasone furoate is a newer corticoid that has high potency but low systemic toxicity. Pharmaceutical factors are known to significantly influence potency and systemic absorption of topically applied glucocorticoids. We studied the potency of "Elocon", a topical formulation of mometasone furoate, compared with two other branded formulations of the same corticoid. METHODS: Corticoid potency was measured by employing a pharmacodynamic parameter of an inhibitory effect of the corticoid on post-ischemic-reactive-hyperemic-response (PIRHR in human forearm skin under occlusive dressing. The PIRHR was expressed in terms of % increase in the skin blood flow (SBF as measured with laser doppler velocimetry (LDV. RESULTS : All three active branded formulations of mometasone furoate produced significant inhibition of PIRHR. The AUC(0-2min of PIRHR was ( Mean ± SEM , Control = 213.52 ± 11.80, Placebo = 209.77 ± 19.31, Formulation A = 119.83 ± 13.71, Formulation C = 53.67 ± 4.85 and Formulation D = 111.46 ± 22.87. Formulation "C" exhibited significantly higher topical anti-inflammatory potency than formulations "A" or "D". CONCLUSIONS: Thus, branded formulations of the same glucocorticoid, mometasone furoate significantly differed in their topical anti-inflammatory potency. "Elocon" was significantly more potent than the two other branded formulations studied.

  4. Potency after permanent prostate brachytherapy for localized prostate cancer

    International Nuclear Information System (INIS)

    Potters, Louis; Torre, Taryn; Fearn, Paul A.; Leibel, Steven A.; Kattan, Michael W.

    2001-01-01

    Purpose: The evaluation of potency preservation after treatment of localized prostate cancer with transperineal permanent prostate brachytherapy (PPB) and the efficacy of sildenafil were studied. Methods and Materials: This study comprised 482 patients who were able to maintain an erection suitable for intercourse before treatment from a cohort of 1166 patients with clinically localized prostate cancer treated with PPB. All patients have been followed prospectively, and actuarial analysis was performed to assess potency preservation over time. Patients treated with sildenafil were evaluated as to its efficacy. Results: The median follow-up of this cohort was 34 months (6-92), with a median age of 68 years (47-80). Potency was preserved in 311 of the 482 patients, with a 5-year actuarial potency rate of 52.7%. The 5-year actuarial potency rate for patients treated with PPB as monotherapy was 76%, and, for those treated with combination external beam radiotherapy (EBT) + PPB, 56% (p=0.08). Patients treated with neoadjuvant androgen deprivation (NAAD) + PPB had a 5-year potency rate of 52%, whereas those with combination EBT + PPB + NAAD had a potency rate of 29% (p=0.13). Cox regression analysis identified that pretreatment use of NAAD and patient age predicted for impotence (p=0.0001 and 0.04, respectively). Of 84 patients treated with sildenafil, 52 had a successful outcome (62%). The response to sildenafil was significantly better in those patients not treated with NAAD (p=0.04). Conclusions: The actuarial potency rates at 5 years for patients treated with PPB are lower than generally acknowledged, except for those patients treated with PPB as monotherapy. Patients who received sildenafil exhibited improved potency in a majority of cases

  5. Potency of Mangrove Apple (Sonneratia alba as Mercury Bioindicator

    Directory of Open Access Journals (Sweden)

    Muhammad Reza Cordova

    2017-12-01

    Full Text Available The anthropogenic provide a negative impact on the surrounding environment. Mangrove species, such as Sonneratia alba would get the impact of anthropogenic activities, to accumulate the pollution of heavy metals. The aim of this study were to evaluate mercury accumulation in Mangrove Apple (S. alba and to analyze mangrove apple potency as mercury bioindicator. Samples were taken in April 2016 at Pari Island, Seribu Islands by purposive sampling. The results showed that the highest concentration of Hg in the Northern of Pari Island was found in the leaves and the lowest was in the fruit. The highest concentration of Hg in the Eastern of Pari Island was found in the leaves and lowest was in the fruit. The concentrations of Hg in the Eastern area higher the Northern area (significantly different. The accumulation of Hg mainly collected on the leaves with TF> 1, but the ability of S. alba trees absorb Hg in the environment showed a small value, namely BCF <1. The ability of S. alba in sediments, contaminated with mercury showed a high value of the leaves in the East Pari Island, but the fruit of S. alba both in the North and East of the Pari Island showed a small value.  Mangrove Apple leaves has a potency as mercury bioindicator organ.

  6. A study on relation between nitroxyl radical reduction potency and X-ray irradiation on mouse lung using L-band electron spin resonance

    International Nuclear Information System (INIS)

    Taneike, Makoto; Sho, Keizen; Morita, Rikushi

    1999-01-01

    Changes in nitroxy radical reduction potency (''reduction potency''), caused by different doses and different number of fractions of X-ray irradiation were studied using a L-band electron spin resonance system on mouse lungs into which 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (hydroxy-TEMPO) was introduced through the trachea. The ''reduction potency'' lineally decreased as the irradiation dose increased from 1.0 to 5.0 Gy, but no further decrease was observed at higher doses of 7.5 and 10 Gy. The reduction potency'' dropped at 20 min after each irradiation, but it recovered to the control levels after 1 week in all 3 groups of single dose of 10 Gy, 3 fractions and 5 fractions in a similar manner. Although the levels of the ''reduction potency'' were kept high in the groups of fractionated irradiation through 1-4 weeks after irradiation, the levels dropped again in the single dose group at 1 week and the levels were kept significantly low until 4 weeks after irradiation. suggesting that the fractionation of X-ray irradiation would also be effective to prevent the deterioration of the ''reduction potency''. Pre-treatment with sufficient ascorbic acid inhibited the lowering effects of radiation on the ''reduction potency'' in a dose dependent manner. Furthermore the levels of the reduction potency'' ever elevated higher than those of controls with the large amount of ascorbic acid of 750 mg/kg or more, suggesting that the large amounts of ascorbic acid could prevent the adverse effects associated with radiation therapy for the lung malignancy. (author)

  7. Serum concentration of alpha-1 antitrypsin is significantly higher in colorectal cancer patients than in healthy controls

    International Nuclear Information System (INIS)

    Pérez-Holanda, Sergio; Blanco, Ignacio; Menéndez, Manuel; Rodrigo, Luis

    2014-01-01

    The association between alpha-1 antitrypsin (AAT) deficiency and colorectal cancer (CRC) is currently controversial. The present study compares AAT serum concentrations and gene frequencies between a group of CRC patients and a control group of healthy unrelated people (HUP). 267 CRC subjects (63% males, 72 ± 10 years old) were enlisted from a Hospital Clinic setting in Asturias, Spain. The HUP group comprised 327 subjects (67% males, mean age 70 ± 7.5 years old) from the same geographical region. Outcome measures were AAT serum concentrations measured by nephelometry, and AAT phenotyping characterization by isoelectric focusing. Significantly higher serum concentrations were found among CRC (208 ± 60) than in HUP individuals (144 ± 20.5) (p = 0.0001). No differences were found in the phenotypic distribution of the Pi*S and Pi*Z allelic frequencies (p = 0.639), although the frequency of Pi*Z was higher in CRC (21%) than in HUP subjects (15%). The only statistically significant finding in this study was the markedly higher AAT serum concentrations found in CRC subjects compared with HUP controls, irrespective of whether their Pi* phenotype was normal (Pi*MM) or deficient (Pi*MS, Pi*MZ and Pi*SZ). Although there was a trend towards the more deficient Pi* phenotype the more advanced the tumor, the results were inconclusive due to the small sample size. Consequently, more powerful studies are needed to reach firmer conclusions on this matter

  8. Dental pulp-derived stromal cells exhibit a higher osteogenic potency than bone marrow-derived stromal cells in vitro and in a porcine critical-size bone defect model

    DEFF Research Database (Denmark)

    Jensen, Jonas; Tvedesøe, Claus; Rölfing, Jan Hendrik Duedal

    2016-01-01

    marrow and the molar teeth of each pig, respectively. BMSCs and DPSCs were cultured in monolayer and on a three-dimensional (3D) polycaprolactone (PCL) - hyaluronic acid - tricalcium phosphate (HT-PCL) scaffold. Population doubling (PD), alkaline phosphatase (ALP) activity, and calcium deposition were...... measured in monolayer. In the 3D culture ALP activity, DNA content, and calcium deposition were evaluated. Six non-penetrating critical-size defects were made in each calvarium of 14 pigs. Three paired sub-studies were conducted: (1) empty defects vs. HT-PCL scaffolds; (2) PCL scaffolds vs. HT...... a higher ALP activity and calcium deposition of the DPSC cultures compared with BMSC cultures. Significantly more bone was present in the HT-PCL group than in both the pure PCL scaffold group and the empty defect group in vivo. DPSCs generated more bone than BMSCs when seeded on HT-PCL. In conclusion...

  9. Water Exchange Produces Significantly Higher Adenoma Detection Rate Than Water Immersion: Pooled Data From 2 Multisite Randomized Controlled Trials.

    Science.gov (United States)

    Leung, Felix W; Koo, Malcolm; Cadoni, Sergio; Falt, Premysl; Hsieh, Yu-Hsi; Amato, Arnaldo; Erriu, Matteo; Fojtik, Petr; Gallittu, Paolo; Hu, Chi-Tan; Leung, Joseph W; Liggi, Mauro; Paggi, Silvia; Radaelli, Franco; Rondonotti, Emanuele; Smajstrla, Vit; Tseng, Chih-Wei; Urban, Ondrej

    2018-03-02

    To test the hypothesis that water exchange (WE) significantly increases adenoma detection rates (ADR) compared with water immersion (WI). Low ADR was linked to increased risk for interval colorectal cancers and related deaths. Two recent randomized controlled trials of head-to-head comparison of WE, WI, and traditional air insufflation (AI) each showed that WE achieved significantly higher ADR than AI, but not WI. The data were pooled from these 2 studies to test the above hypothesis. Two trials (5 sites, 14 colonoscopists) that randomized 1875 patients 1:1:1 to AI, WI, or WE were pooled and analyzed with ADR as the primary outcome. The ADR of AI (39.5%) and WI (42.4%) were comparable, significantly lower than that of WE (49.6%) (vs. AI P=0.001; vs. WI P=0.033). WE insertion time was 3 minutes longer than that of AI (Prate (vs. AI) of the >10 mm advanced adenomas. Right colon combined advanced and sessile serrated ADR of AI (3.4%) and WI (5%) were comparable and were significantly lower than that of WE (8.5%) (vs. AI P<0.001; vs. WI P=0.039). Compared with AI and WI, the superior ADR of WE offsets the drawback of a significantly longer insertion time. For quality improvement focused on increasing adenoma detection, WE is preferred over WI. The hypothesis that WE could lower the risk of interval colorectal cancers and related deaths should be tested.

  10. Dental pulp-derived stromal cells exhibit a higher osteogenic potency than bone marrow-derived stromal cells in vitro and in a porcine critical-size bone defect model

    Directory of Open Access Journals (Sweden)

    Jensen Jonas

    2016-01-01

    Full Text Available Introduction: The osteogenic differentiation of bone marrow-derived mesenchymal stromal cells (BMSCs was compared with that of dental pulp-derived stromal cells (DPSCs in vitro and in a pig calvaria critical-size bone defect model. Methods: BMSCs and DPSCs were extracted from the tibia bone marrow and the molar teeth of each pig, respectively. BMSCs and DPSCs were cultured in monolayer and on a three-dimensional (3D polycaprolactone (PCL – hyaluronic acid – tricalcium phosphate (HT-PCL scaffold. Population doubling (PD, alkaline phosphatase (ALP activity, and calcium deposition were measured in monolayer. In the 3D culture ALP activity, DNA content, and calcium deposition were evaluated. Six non-penetrating critical-size defects were made in each calvarium of 14 pigs. Three paired sub-studies were conducted: (1 empty defects vs. HT-PCL scaffolds; (2 PCL scaffolds vs. HT-PCL scaffolds; and (3 autologous BMSCs on HT-PCL scaffolds vs. autologous DPSCs on HT-PCL scaffolds. The observation time was five weeks. Bone volume fractions (BV/TV were assessed with micro-computed tomography (μCT and histomorphometry. Results and discussion: The results from the in vitro study revealed a higher ALP activity and calcium deposition of the DPSC cultures compared with BMSC cultures. Significantly more bone was present in the HT-PCL group than in both the pure PCL scaffold group and the empty defect group in vivo. DPSCs generated more bone than BMSCs when seeded on HT-PCL. In conclusion, DPSCs exhibited a higher osteogenic potential compared with BMSCs both in vitro and in vivo, making it a potential cell source for future bone tissue engineering.

  11. ANTIOXIDANT POTENCY OF WATER KEFIR

    Directory of Open Access Journals (Sweden)

    Muneer Alsayadi M.S.

    2013-06-01

    Full Text Available Reactive oxygen species (ROS have strong relationship with several diseases. Many fermented foods were reported to be important sources for antioxidant compounds. Antioxidant activity of water kefir never reported in the scientific literature. The objective of this study was to detect and investigate the antioxidant potency of water kefir. Water kefir was prepared by fermentation of sugar solution with kefir grains for 24h. Antioxidant activity of fresh water kefir drink and its extract with (0.125–5 mg/ml was evaluated using 2,2,-diphenyl-1-pricrylhydrozyl (DPPH scavenging method, and inhibition of ascorbate autoxidation and the reducing power of water kefir were determined, Butylated hydroxyanisole (BHA and ascorbic acid were used for comparison. Water kefir demonstrated great ability to DPPH scavenging ranged (9.88-63.17%. And inhibit ascorbate oxidation by (6.08-25.57% increased in consequent with concentration raising. These results prime to conclude that water kefir could be promisor source of natural antioxidants with good potency in health developing.

  12. Rib fractures and their association With solid organ injury: higher rib fractures have greater significance for solid organ injury screening.

    Science.gov (United States)

    Rostas, Jack W; Lively, Timothy B; Brevard, Sidney B; Simmons, Jon D; Frotan, Mohammad A; Gonzalez, Richard P

    2017-04-01

    The purpose of this study was to identify patients with rib injuries who were at risk for solid organ injury. A retrospective chart review was performed of all blunt trauma patients with rib fractures during the period from July 2007 to July 2012. Data were analyzed for association of rib fractures and solid organ injury. In all, 1,103 rib fracture patients were identified; 142 patients had liver injuries with 109 (77%) associated right rib fractures. Right-sided rib fractures with highest sensitivity for liver injury were middle rib segment (5 to 8) and lower segment (9 to 12) with liver injury sensitivities of 68% and 43%, respectively (P rib fractures. Left middle segment rib fractures and lower segment rib fractures had sensitivities of 80% and 63% for splenic injury, respectively (P Rib fractures higher in the thoracic cage have significant association with solid organ injury. Using rib fractures from middle plus lower segments as indication for abdominal screening will significantly improve rib fracture sensitivity for identification of solid organ injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Tribes and Territories in the 21st Century: Rethinking the Significance of Disciplines in Higher Education. International Studies in Higher Education

    Science.gov (United States)

    Trowler, Paul, Ed.; Saunders, Murray, Ed.; Bamber, Veronica, Ed.

    2012-01-01

    The "tribes and territories" metaphor for the cultures of academic disciplines and their roots in different knowledge characteristics has been used by those interested in university life and work since the early 1990s. This book draws together research, data and theory to show how higher education has gone through major change since then…

  14. A Review of OIE Country Status Recovery Using Vaccinate-to-Live Versus Vaccinate-to-Die Foot-and-Mouth Disease Response Policies I: Benefits of Higher Potency Vaccines and Associated NSP DIVA Test Systems in Post-Outbreak Surveillance.

    Science.gov (United States)

    Barnett, P V; Geale, D W; Clarke, G; Davis, J; Kasari, T R

    2015-08-01

    To rapidly return to trade, countries with OIE status, FMD-free country where vaccination is not practised, have destroyed emergency vaccinated animals, raising ethical concerns with respect to social values, the environment, animal welfare and global food security. This two-part review explores whether science could support eligibility to return to previous OIE status in 3 months irrespective of vaccinate-to-live or vaccinate-to-die policies. Here, we examine the benefits of higher potency (≥ 6 PD50 ), high-purity vaccines formulated from antigen banks for emergency use, their efficacy and performance in differentiating infected from vaccinated animals (DIVA) assays for post-outbreak surveillance. From an intensive programme of research, we conclude that high-quality, higher potency vaccines are proven to reduce FMD virus (FMDV) subclinical circulation and the risk of carriers. Broader coverage than predicted by serology suggests the potential to hold a few 'key' vaccine strains improving logistics and reducing the financial burden of antigen banks. The OIE should adopt formal definitions for emergency vaccination and emergency vaccines. In terms of supportive tools, we consider that the lack of OIE recognition of DIVA tests other than those of PANAFTOSA in cattle is a shortcoming. There is need for research on maternal antibody interference with DIVA tests and on the use of such tests to establish whether greater purification of vaccines improves performance. We consider that alignment of waiting periods for vaccinate-to-live and vaccinate-to-die in OIE Code Article 8.5.9 1 b. and c. is feasible until an acceptable level of statistical certainty for surveillance or target probability of freedom is established to substantiate the absence of FMDV infection or circulation. It is surveillance intensity rather than waiting periods that establishes the risk of residual FMDV. EU Directive 2003/85/EC implicitly recognizes this, permitting derogation of the OIE waiting

  15. Human isolates of Salmonella enterica serovar Typhimurium from Taiwan displayed significantly higher levels of antimicrobial resistance than those from Denmark.

    Science.gov (United States)

    Torpdahl, Mia; Lauderdale, Tsai-Ling; Liang, Shiu-Yun; Li, Ishien; Wei, Sung-Hsi; Chiou, Chien-Shun

    2013-02-01

    Salmonella enterica serovar Typhimurium is a major zoonotic pathogen with a high prevalence of antimicrobial resistance. This pathogen can disseminate across borders and spread far distances via the food trade and international travel. In this study, we compared the genotypes and antimicrobial resistance of 378 S. Typhimurium isolates collected in Taiwan and Denmark between 2009 and 2010. Genotyping revealed that many S. Typhimurium strains were concurrently circulating in Taiwan, Denmark and other countries in 2009 and 2010. When compared to the isolates collected from Denmark, the isolates from Taiwan displayed a significantly higher level of resistance to 11 of the 12 tested antimicrobials. Seven genetic clusters (A-G) were designated for the isolates. A high percentage of the isolates in genetic clusters C, F and G were multidrug-resistant. Of the isolates in cluster C, 79.2% were ASSuT-resistant, characterized by resistance to ampicillin, streptomycin, sulfamethoxazole, and tetracycline. In cluster F, 84.1% of the isolates were ACSSuT-resistant (resistant to ASSuT and chloramphenicol). Cluster G was unique to Taiwan and characterized in most isolates by the absence of three VNTRs (ST20, ST30 and STTR6) as well as a variety of multidrug resistance profiles. This cluster exhibited very high to extremely high levels of resistance to several first-line drugs, and among the seven clusters, it displayed the highest levels of resistance to cefotaxime and ceftazidime, ciprofloxacin and gentamicin. The high prevalence of antimicrobial resistance in S. Typhimurium from Taiwan highlights the necessity to strictly regulate the use of antimicrobials in the agriculture and human health care sectors. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Protective effects of high-potency FMDV O

    NARCIS (Netherlands)

    Horsington, Jacquelyn; Perez, Claudia Beascoechea; Maradei, Eduardo; Novo, Sabrina Galdo; Gonzales, Jose L.; Singanallur, Nagendrakumar B.; Bonastre, Paula; Vosloo, Wilna

    2017-01-01

    Serotype O foot-and-mouth disease (FMD) virus belonging to the SEA topotype continues to be a significant problem in the Eastern Asia region, with outbreaks in Japan and South Korea resulting in the culling of over 3.5 million cattle and pigs in recent years. High-potency O1 Manisa vaccine was

  17. Higher Education in the United Arab Emirates: An Analysis of the Outcomes of Significant Increases in Supply and Competition

    Science.gov (United States)

    Wilkins, Stephen

    2010-01-01

    During the last decade, several countries across the Middle and Far East have established higher education hubs, some of which have grown rapidly by attracting foreign universities to set up international branch campuses. The United Arab Emirates (UAE) is by far the largest host of international branch campuses globally, having over 40 providers…

  18. Accreditation and Its Significance for Programs of Higher Education in Criminology and Criminal Justice: A Review of the Literature.

    Science.gov (United States)

    Simpson, Antony E.

    The development of minimum standards in higher education through the evolution of accreditation in specialized disciplines, and standard setting in criminology and criminal justice education are examined. The very different experiences with the concept of accreditation encountered in the fields of public administration and law are considered. Law…

  19. Sexual Function and the Use of Medical Devices or Drugs to Optimize Potency After Prostate Brachytherapy

    International Nuclear Information System (INIS)

    Whaley, J. Taylor; Levy, Lawrence B.; Swanson, David A.; Pugh, Thomas J.; Kudchadker, Rajat J.; Bruno, Teresa L.; Frank, Steven J.

    2012-01-01

    Purpose: Prospective evaluation of sexual outcomes after prostate brachytherapy with iodine-125 seeds as monotherapy at a tertiary cancer care center. Methods and Materials: Subjects were 129 men with prostate cancer with I-125 seed implants (prescribed dose, 145 Gy) without supplemental hormonal or external beam radiation therapy. Sexual function, potency, and bother were prospectively assessed at baseline and at 1, 4, 8, and 12 months using validated quality-of-life self-assessment surveys. Postimplant dosimetry values, including dose to 10% of the penile bulb (D10), D20, D33, D50, D75, D90, and penile volume receiving 100% of the prescribed dose (V100) were calculated. Results: At baseline, 56% of patients recorded having optimal erections; at 1 year, 62% of patients with baseline erectile function maintained optimal potency, 58% of whom with medically prescribed sexual aids or drugs. Variables associated with pretreatment-to-posttreatment decline in potency were time after implant (p = 0.04) and age (p = 0.01). Decline in urinary function may have been related to decline in potency. At 1 year, 69% of potent patients younger than 70 years maintained optimal potency, whereas 31% of patients older than 70 maintained optimal potency (p = 0.02). Diabetes was related to a decline in potency (p = 0.05), but neither smoking nor hypertension were. For patients with optimal potency at baseline, mean sexual bother scores had declined significantly at 1 year (p < 0.01). Sexual potency, sexual function, and sexual bother scores failed to correlate with any dosimetric variable tested. Conclusions: Erections firm enough for intercourse can be achieved at 1 year after treatment, but most men will require medical aids to optimize potency. Although younger men were better able to maintain erections firm enough for intercourse than older men, there was no correlation between potency, sexual function, or sexual bother and penile bulb dosimetry.

  20. Sexual Function and the Use of Medical Devices or Drugs to Optimize Potency After Prostate Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Whaley, J. Taylor; Levy, Lawrence B. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Swanson, David A. [Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Pugh, Thomas J. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Kudchadker, Rajat J.; Bruno, Teresa L. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Frank, Steven J., E-mail: sjfrank@mdnaderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States)

    2012-04-01

    Purpose: Prospective evaluation of sexual outcomes after prostate brachytherapy with iodine-125 seeds as monotherapy at a tertiary cancer care center. Methods and Materials: Subjects were 129 men with prostate cancer with I-125 seed implants (prescribed dose, 145 Gy) without supplemental hormonal or external beam radiation therapy. Sexual function, potency, and bother were prospectively assessed at baseline and at 1, 4, 8, and 12 months using validated quality-of-life self-assessment surveys. Postimplant dosimetry values, including dose to 10% of the penile bulb (D10), D20, D33, D50, D75, D90, and penile volume receiving 100% of the prescribed dose (V100) were calculated. Results: At baseline, 56% of patients recorded having optimal erections; at 1 year, 62% of patients with baseline erectile function maintained optimal potency, 58% of whom with medically prescribed sexual aids or drugs. Variables associated with pretreatment-to-posttreatment decline in potency were time after implant (p = 0.04) and age (p = 0.01). Decline in urinary function may have been related to decline in potency. At 1 year, 69% of potent patients younger than 70 years maintained optimal potency, whereas 31% of patients older than 70 maintained optimal potency (p = 0.02). Diabetes was related to a decline in potency (p = 0.05), but neither smoking nor hypertension were. For patients with optimal potency at baseline, mean sexual bother scores had declined significantly at 1 year (p < 0.01). Sexual potency, sexual function, and sexual bother scores failed to correlate with any dosimetric variable tested. Conclusions: Erections firm enough for intercourse can be achieved at 1 year after treatment, but most men will require medical aids to optimize potency. Although younger men were better able to maintain erections firm enough for intercourse than older men, there was no correlation between potency, sexual function, or sexual bother and penile bulb dosimetry.

  1. Sterol 27-Hydroxylase Polymorphism Significantly Associates With Shorter Telomere, Higher Cardiovascular and Type-2 Diabetes Risk in Obese Subjects

    Directory of Open Access Journals (Sweden)

    Sofia Pavanello

    2018-06-01

    Full Text Available Background/objectivesThe pathologic relationship linking obesity and lipid dismetabolism with earlier onset of aging-related disorders, including cardiovascular disease (CVD and type-2 diabetes (T2D, is not fully elucidate. Chronic inflammatory state, in obese individuals, may accelerate cellular aging. However, leukocyte telomere length (LTL, the cellular biological aging indicator, is elusively linked with obesity. Recent studies indicate that sterol 27-hydroxylase (CYP27A1 is an emerging antiatherogenic enzyme, that, by converting extrahepatic cholesterol to 27-hydroxycholesterol, facilitates cholesterol removal via high-density lipoprotein-cholesterol (HDL-C. We tested the hypothesis that obese subjects who carry at least three copies of CYP27A1 low-hydroxylation (LH activity genome-wide-validated alleles (rs4674345A, rs1554622A, and rs4674338G present premature aging, as reflected in shorter LTL and higher levels of CVD/T2D risk factors, including reduced HDL-C.Subjects/methodsObese subjects from SPHERE project {n = 1,457; overweight [body mass index (BMI 25–30 kg/m2] 65.8% and severe-obese (BMI > 30 kg/m2 34.2%} were characterized for the presence from 0 to 6 LH-CYP27A1 allele copy number. Univariate and multivariable sex–age–smoking-adjusted linear-regression models were performed to compare CVD/T2D risk factors and biological aging (LTL in relation to the combined BMI-LH groups: overweight-LH: 0–2, overweight-LH: 3–6, severe-obese-LH: 0–2, and severe-obese-LH: 3–6.ResultsHigher LTL attrition was found in severe-obese than overweight individuals (p < 0.001. Multivariable model reveals that among severe-obese patients those with LH: 3–6 present higher LTL attrition than LH: 0–2 (p < 0.05. Univariate and multivariable models remarkably show that insulin resistance is higher both in overweight-LH: 3–6 vs overweight-LH: 0–2 (p < 0.001 and in severe-obese-LH: 3–6 vs severe-obese-LH: 0–2 (p

  2. The H3 antagonist ABT-288 is tolerated at significantly higher exposures in subjects with schizophrenia than in healthy volunteers.

    Science.gov (United States)

    Othman, Ahmed A; Haig, George; Florian, Hana; Locke, Charles; Gertsik, Lev; Dutta, Sandeep

    2014-06-01

    ABT-288 is a potent and selective H3 receptor antagonist with procognitive effects in several preclinical models. In previous studies, 3 mg once daily was the maximal tolerated dose in healthy volunteers. This study characterized the safety, tolerability and pharmacokinetics of ABT-288 in stable subjects with schizophrenia. This was a randomized, double-blind, placebo-controlled, dose-escalating study of ABT-288 (10 dose levels, from 1 to 60 mg once daily for 14 days) in stable subjects with schizophrenia treated with an atypical antipsychotic. In each dose group, five to seven and two to three participants were assigned to ABT-288 and placebo, respectively. Of the 67 participants enrolled, nine participants (on ABT-288) were prematurely discontinued, in seven of these due to adverse events. ABT-288 was generally safe and tolerated at doses up to 45 mg once daily. The most common adverse events, in decreasing frequency (from 31 to 5%), were abnormal dreams, headache, insomnia, dizziness, somnolence, dysgeusia, dry mouth, psychotic disorder, parosmia and tachycardia. Adverse events causing early termination were psychotic events (four) and increased creatine phosphokinase, pyrexia and insomnia (one each). The half-life of ABT-288 ranged from 28 to 51 h, and steady state was achieved by day 12 of dosing. At comparable multiple doses, ABT-288 exposure in subjects with schizophrenia was 45% lower than that previously observed in healthy subjects. At trough, ABT-288 cerebrospinal fluid concentrations were 40% of the total plasma concentrations. ABT-288 was tolerated at a 15-fold higher dose and 12-fold higher exposures in subjects with schizophrenia than previously observed in healthy volunteers. The greater ABT-288 tolerability was not due to limited brain uptake. © 2013 The British Pharmacological Society.

  3. Sources of Inspiration: The role of significant persons in young people's choice of science in higher education

    Science.gov (United States)

    Sjaastad, Jørgen

    2012-07-01

    The objectives of this article were to investigate to which extent and in what ways persons influence students' choice of science, technology, engineering, and mathematics (STEM) in tertiary education, and to assess the suitability of an analytical framework for describing this influence. In total, 5,007 Norwegian STEM students completed a questionnaire including multiple-choice as well as open-ended questions about sources of inspiration for their educational choice. Using the conceptualisation of significant persons suggested by Woelfel and Haller, the respondents' descriptions of parents and teachers are presented in order to elaborate on the different ways these significant persons influence a STEM-related educational choice. Parents engaged in STEM themselves are models, making the choice of STEM familiar, and they help youngsters define themselves through conversation and support, thus being definers. Teachers are models by displaying how STEM might bring fulfilment in someone's life and by giving pupils a positive experience with the subjects. They help young people discover their STEM abilities, thus being definers. Celebrities are reported to have minor influence on STEM-related educational choices. Both qualitative and quantitative analyses indicate that interpersonal relationships are key factors in order to inspire and motivate a choice of STEM education. Implications for recruitment issues and for research on interpersonal influence are discussed. It is suggested that initiatives to increase recruitment to STEM might be aimed at parents and other persons in interpersonal relationships with youth as a target group.

  4. Plucking the Golden Goose: Higher Royalty Rates on the Oil Sands Generate Significant Increases in Government Revenue

    Directory of Open Access Journals (Sweden)

    Kenneth J. McKenzie

    2011-09-01

    Full Text Available The Alberta government’s 2009 New Royalty Framework elicited resistance on the part of the energy industry, leading to subsequent reductions in the royalties imposed on natural gas and conventional oil. However, the oil sands sector, subject to different terms, quickly accepted the new arrangement with little complaint, recognizing it as win-win situation for industry and the government. Under the framework, Alberta recoups much more money in royalties — about $1 billion over the two year period of 2009 and 2010 — without impinging significantly on investment in the oil sands. This brief paper demonstrates that by spreading the financial risks and benefits to everyone involved, the new framework proves it’s possible to generate increased revenue without frightening off future investment. The same model could conceivably be applied to the conventional oil and natural gas sectors.

  5. Low Carbon Rice Farming Practices in the Mekong Delta Yield Significantly Higher Profits and Lower Greenhouse Gas Emissions

    Science.gov (United States)

    Rudek, J.; Van Sanh, N.; Tinh, T. K.; Tin, H. Q.; Thu Ha, T.; Pha, D. N.; Cui, T. Q.; Tin, N. H.; Son, N. N.; Thanh, H. H.; Kien, H. T.; Kritee, K.; Ahuja, R.

    2014-12-01

    The Vietnam Low-Carbon Rice Project (VLCRP) seeks to significantly reduce GHG emissions from rice cultivation, an activity responsible for more than 30% of Vietnam's overall GHG emissions, while improving livelihoods for the rice farmer community by decreasing costs and enhancing yield as well as providing supplemental farmer income through the sale of carbon credits. The Mekong Delta makes up 12% of Vietnam's land area, but produces more than 50% of the country's rice, including more than 90% of the rice for export. Rice cultivation is the main source of income for 80% of farmers in the Mekong Delta. VLCRP was launched in late 2012 in the Mekong Delta in two major rice production provinces, Kien Giang and An Giang. To date, VLCRP has completed 11 crop seasons (in Kien Giang and An Giang combined), training over 400 farmer households in applying VLCRP's package of practices (known as 1 Must - 6 Reductions) and building technical capacity to its key stakeholders and rice farmer community leaders. By adopting the 1 Must- 6 Reductions practices (including reduced seeding density, reduced fertilizer and pesticide application, and alternative wetting and drying water management), rice farmers reduce their input costs while maintaining or improving yields, and decreasing greenhouse gas emissions. The VLCRP package of practices also deliver other environmental and social co-benefits, such as reduced water pollution, improved habitat for fishery resources and reduced health risks for farmers through the reduction of agri-chemicals. VLCRP farmers use significantly less inputs (50% reduction in seed, 30% reduction in fertilizer, 40-50% reduction in water) while improving yields 5-10%, leading to an increase in profit from 10% to as high as 60% per hectare. Preliminary results indicate that the 1 Must- 6 Reductions practices have led to approximately 40-65% reductions in greenhouse gas emissions, equivalent to 4 tons of CO2e/ha/yr in An Giang and 35 tons of CO2e/ha/yr in Kien

  6. Potency preservation following stereotactic body radiation therapy for prostate cancer

    International Nuclear Information System (INIS)

    Obayomi-Davies, Olusola; Pahira, John; McGeagh, Kevin G; Collins, Brian T; Kowalczyk, Keith; Bandi, Gaurav; Kumar, Deepak; Suy, Simeng; Dritschilo, Anatoly; Lynch, John H; Collins, Sean P; Chen, Leonard N; Bhagat, Aditi; Wright, Henry C; Uhm, Sunghae; Kim, Joy S; Yung, Thomas M; Lei, Siyuan; Batipps, Gerald P

    2013-01-01

    Erectile dysfunction after prostate radiation therapy remains an ongoing challenge and critical quality of life issue. Given the higher dose of radiation per fraction using stereotactic body radiation therapy (SBRT) there is concern that post-SBRT impotency would be higher than conventional radiation therapy approaches. This study sought to evaluate potency preservation and sexual function following SBRT for prostate cancer. Between February 2008 and March 2011, 216 men with clinically localized prostate cancer were treated definitively with SBRT monotherapy at Georgetown University Hospital. Potency was defined as the ability to have an erection firm enough for intercourse with or without sexual aids while sexual activity was defined as the ability to have an erection firm enough for masturbation and foreplay. Patients who received androgen deprivation therapy (ADT) were excluded from this study. Ninety-seven hormone-naïve men were identified as being potent at the initiation of therapy and were included in this review. All patients were treated to 35–36.25 Gy in 5 fractions delivered with the CyberKnife Radiosurgical System (Accuray). Prostate specific antigen (PSA) and total testosterone levels were obtained pre-treatment, every 3 months for the first year and every 6 months for the subsequent year. Sexual function was assessed with the Sexual Health Inventory for Men (SHIM), the Expanded Prostate Index Composite (EPIC)-26 and Utilization of Sexual Medication/Device questionnaires at baseline and all follow-up visits. Ninety-seven men (43 low-, 50 intermediate- and 4 high-risk) at a median age of 68 years (range, 48–82 years) received SBRT. The median pre-treatment PSA was 5.9 ng/ml and the minimum follow-up was 24 months. The median pre-treatment total serum testosterone level was 11.4 nmol/L (range, 4.4-27.9 nmol/L). The median baseline SHIM was 22 and 36% of patients utilized sexual aids prior to treatment. Although potency rates declined following

  7. Correlation of liquid chromatographic and biological assay for potency assessment of filgrastim and related impurities.

    Science.gov (United States)

    Skrlin, Ana; Kosor Krnic, Ela; Gosak, Darko; Prester, Berislav; Mrsa, Vladimir; Vuletic, Marko; Runac, Domagoj

    2010-11-02

    In vivo and in vitro potency assays have always been a critical tool for confirmation of protein activity. However, due to their complexity and time consuming procedures, it remains a challenge to find an alternative analytical approach that would enable their replacement with no impact on the quality of provided information. The goal of this research was to determine if a correlation between liquid chromatography assays and in vitro biological assay could be established for filgrastim (recombinant human granulocyte-colony stimulating factor, rhG-CSF) samples containing various amounts of related impurities. For that purpose, relevant filgrastim related impurities were purified to homogeneity and characterized by liquid chromatography and mass spectrometry. A significant correlation (R(2)>0.90) between the two types of assays was revealed. Potency of oxidized filgrastim was determined to be approximately 25% of filgrastim stated potency (1 x 10(8)IU/mg of protein). Formyl-methionine filgrastim had potency of 89% of the filgrastim stated potency, while filgrastim dimer had 67% of filgrastim stated potency. A mathematical model for the estimation of biological activity of filgrastim samples from chromatography data was established and a significant correlation between experimental potency values and potency values estimated by the mathematical model was obtained (R(2)=0.92). Based on these results a conclusion was made that reversed phase high performance liquid chromatography could be used as an alternative for the in vitro biological assay for potency assessment of filgrastim samples. Such an alternative model would enable substitution of a complex and time consuming biological assay with a robust and precise instrumental method in many practical cases. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  8. Comparative analysis of the intracerebral mouse protection test and serological method for potency assays of pertussis component in DTP vaccine

    Directory of Open Access Journals (Sweden)

    Denise Cristina Souza Matos

    2012-06-01

    Full Text Available The aim of this study was to compare the PSPT standardized in-house as an alternative to MPT for potency assays of pertussis component. Statistical analyses have showed similar pertussis potency values when PSPT was compared to MPT. Significant correlation between the potency results obtained by in vivo and in vitro assays was also been observed. Results by PSPT have demonstrated reproducibility and accuracy for potency pertussis control and this approach has been considered promising for use at least during the steps of production.

  9. Kinetic microplate bioassays for relative potency of antibiotics improved by partial Least Square (PLS) regression.

    Science.gov (United States)

    Francisco, Fabiane Lacerda; Saviano, Alessandro Morais; Almeida, Túlia de Souza Botelho; Lourenço, Felipe Rebello

    2016-05-01

    Microbiological assays are widely used to estimate the relative potencies of antibiotics in order to guarantee the efficacy, safety, and quality of drug products. Despite of the advantages of turbidimetric bioassays when compared to other methods, it has limitations concerning the linearity and range of the dose-response curve determination. Here, we proposed to use partial least squares (PLS) regression to solve these limitations and to improve the prediction of relative potencies of antibiotics. Kinetic-reading microplate turbidimetric bioassays for apramacyin and vancomycin were performed using Escherichia coli (ATCC 8739) and Bacillus subtilis (ATCC 6633), respectively. Microbial growths were measured as absorbance up to 180 and 300min for apramycin and vancomycin turbidimetric bioassays, respectively. Conventional dose-response curves (absorbances or area under the microbial growth curve vs. log of antibiotic concentration) showed significant regression, however there were significant deviation of linearity. Thus, they could not be used for relative potency estimations. PLS regression allowed us to construct a predictive model for estimating the relative potencies of apramycin and vancomycin without over-fitting and it improved the linear range of turbidimetric bioassay. In addition, PLS regression provided predictions of relative potencies equivalent to those obtained from agar diffusion official methods. Therefore, we conclude that PLS regression may be used to estimate the relative potencies of antibiotics with significant advantages when compared to conventional dose-response curve determination. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Interferon-α Subtypes in an Ex Vivo Model of Acute HIV-1 Infection: Expression, Potency and Effector Mechanisms.

    Directory of Open Access Journals (Sweden)

    Michael S Harper

    Full Text Available HIV-1 is transmitted primarily across mucosal surfaces and rapidly spreads within the intestinal mucosa during acute infection. The type I interferons (IFNs likely serve as a first line of defense, but the relative expression and antiviral properties of the 12 IFNα subtypes against HIV-1 infection of mucosal tissues remain unknown. Here, we evaluated the expression of all IFNα subtypes in HIV-1-exposed plasmacytoid dendritic cells by next-generation sequencing. We then determined the relative antiviral potency of each IFNα subtype ex vivo using the human intestinal Lamina Propria Aggregate Culture model. IFNα subtype transcripts from the centromeric half of the IFNA gene complex were highly expressed in pDCs following HIV-1 exposure. There was an inverse relationship between IFNA subtype expression and potency. IFNα8, IFNα6 and IFNα14 were the most potent in restricting HIV-1 infection. IFNα2, the clinically-approved subtype, and IFNα1 were both highly expressed but exhibited relatively weak antiviral activity. The relative potencies correlated with binding affinity to the type I IFN receptor and the induction levels of HIV-1 restriction factors Mx2 and Tetherin/BST-2 but not APOBEC3G, F and D. However, despite the lack of APOBEC3 transcriptional induction, the higher relative potency of IFNα8 and IFNα14 correlated with stronger inhibition of virion infectivity, which is linked to deaminase-independent APOBEC3 restriction activity. By contrast, both potent (IFNα8 and weak (IFNα1 subtypes significantly induced HIV-1 GG-to-AG hypermutation. The results unravel non-redundant functions of the IFNα subtypes against HIV-1 infection, with strong implications for HIV-1 mucosal immunity, viral evolution and IFNα-based functional cure strategies.

  11. Significant determinants of academic performance by new students enrolled in the higher distance education system of Ecuador. The case of the Universidad Técnica Particular de Loja

    Directory of Open Access Journals (Sweden)

    Luis F. Moncada Mora

    2011-12-01

    Full Text Available In this article we present the significant determiners of academic performance of new students enrolled in the higher distance education system of Ecuador. A description and correlation of the variables were undertaken to formalize the probabilistic model that confirms the positive, negative, individual and global effects.

  12. A retrospective evaluation of the efficacy of intravenous bumetanide and comparison of potency with furosemide

    Directory of Open Access Journals (Sweden)

    Nappi JM

    2013-03-01

    Full Text Available Background: The potency of intravenous bumetanide to furosemide using a ratio of 1:40 has been suggested; however, there are little data supporting this ratio. Recent drug shortages required the use of bumetanide in a large patient population, enabling further characterization of the efficacy of IV bumetanide.Objective: The primary objective of this study was to estimate a dose-response effect of IV bumetanide on urine output (UOP in all patients that received 48 hours of therapy as well as in a subgroup of patients with heart failure (HF. This subgroup was used to compare the potency of bumetanide with furosemide. A secondary safety objective described electrolyte replacement required during therapy. Methods: This was a single-center retrospective study examining the dose-response effect of IV bumetanide in patients receiving at least 48 hours of intermittent (iIV or continuous (cIV dosing, measured by UOP per mg of drug received (mL/mg. The potency of IV bumetanide was compared with furosemide in a subset of patients with HF using pre-existing data. The safety of IV bumetanide was analyzed by quantifying electrolyte replacement received during the study period.Results: The primary outcome was higher in the iIV group (n=93 at 1273 ± 844 mL/mg compared with the cIV group (n=16 at 749 ± 370 mL/mg (P=0.002. Among patients with HF who received furosemide (iIV n=30, cIV n=26 or bumetanide (iIV n=30, cIV n=3, a potency ratio of 41:1 was found for the iIV group and 34:1 for all patients with HF. There was no significant difference in electrolyte replacement between groups.Conclusion: A greater response was seen with intermittent bumetanide compared with continuous infusion bumetanide. This study supports the 40:1 dose equivalence ratio (furosemide:bumetanide in patients with HF receiving at least 48 hours of intravenous intermittent bumetanide.

  13. Normal LVEF measurements are significantly higher in females asassessed by post-stress resting Tc-99m sestamibi gated myocardial perfusion SPECT

    International Nuclear Information System (INIS)

    Kim, Jong Ho; Shin, Eak Kyun

    1999-01-01

    Volume-LVEF relationship is one of the most important factors of automatic EF quantification algorithm from gated myocardial perfusion SPECT(gMPS) (Germano et al. JNM, 1995). Gender difference whereby normal LVEF measurements are higher in females assessed by gMPS (Yao et al. JNM 1997). To validate true physiologic value of LVEF vs sampling or measured error, various parameters were evaluated statistically in both gender and age matched 200 subjects (mean age= 58.41±15.01) with normal LVEF more than 50%, and a low likelihood of coronary artery disease. Correlation between LVEDVi(ml/m2) and LVEF was highly significant (r=-0.62, p<0.0001) with similar correlations noted in both male (r=-0.45, p<0.0001) and female (r=-0.67, p<0.0001) subgroups. By multivariate analysis, LV volume and stroke volume was the most significant factor influencing LVEF in male and female, respectively. In conclusion, there is a significant negative correlation between LV volume and LVEF as measured by Tc-99m gated SPECT. Higher normal LVEF value should be applied to females as assessed by post-stress resting Tc-99m Sestamibi gated myocardial perfusion SPECT

  14. Potency of Animal Models in KANSEI Engineering

    Science.gov (United States)

    Ozaki, Shigeru; Hisano, Setsuji; Iwamoto, Yoshiki

    Various species of animals have been used as animal models for neuroscience and provided critical information about the brain functions. Although it seems difficult to elucidate a highly advanced function of the human brain, animal models have potency to clarify the fundamental mechanisms of emotion, decision-making and social behavior. In this review, we will pick up common animal models and point to both the merits and demerits caused by the characteristics. We will also mention that wide-ranging approaches from animal models are advantageous to understand KANSEI as well as mind in humans.

  15. Chemical applicability domain of the local lymph node assay (LLNA) for skin sensitisation potency. Part 4. Quantitative correlation of LLNA potency with human potency.

    Science.gov (United States)

    Roberts, David W; Api, Anne Marie

    2018-07-01

    Prediction of skin sensitisation potential and potency by non-animal methods is the target of many active research programmes. Although the aim is to predict sensitisation potential and potency in humans, data from the murine local lymph node assay (LLNA) constitute much the largest source of quantitative data on in vivo skin sensitisation. The LLNA has been the preferred in vivo method for identification of skin sensitising chemicals and as such is potentially valuable as a benchmark for assessment of non-animal approaches. However, in common with all predictive test methods, the LLNA is subject to false positives and false negatives with an overall level of accuracy said variously to be approximately 80% or 90%. It is also necessary to consider the extent to which, for true positives, LLNA potency correlates with human potency. In this paper LLNA potency and human potency are compared so as to express quantitatively the correlation between them, and reasons for non-agreement between LLNA and human potency are analysed. This leads to a better definition of the applicability domain of the LLNA, within which LLNA data can be used confidently to predict human potency and as a benchmark to assess the performance of non-animal approaches. Copyright © 2018. Published by Elsevier Inc.

  16. The ratio of nurse consultation and physician efficiency index of senior rheumatologists is significantly higher than junior physicians in rheumatology residency training

    DEFF Research Database (Denmark)

    Emamifar, Amir; van Bui Hansen, Morten Hai; Jensen Hansen, Inger Marie

    2017-01-01

    To elucidate the difference between ratios of nurse consultation sought by senior rheumatologists and junior physicians in rheumatology residency training, and also to evaluate physician efficiency index respecting patients with rheumatoid arthritis (RA). Data regarding outpatient visits for RA...... patients between November 2013 and 2015 were extracted. The mean interval (day) between consultations, the nurse/physician visits ratio, and physician efficiency index (nurse/physician visits ratio × mean interval) for each senior and junior physicians were calculated. Disease Activity Score in 28 joints....../physician visits ratio (P = .01) and mean efficiency index (P = .04) of senior rheumatologists were significantly higher than that of junior physicians. Regression analysis showed a positive correlation between physician postgraduate experience and physician efficiency index adjusted for DAS28 at baseline...

  17. Patients with Duchenne muscular dystrophy are significantly shorter than those with Becker muscular dystrophy, with the higher incidence of short stature in Dp71 mutated subgroup.

    Science.gov (United States)

    Matsumoto, Masaaki; Awano, Hiroyuki; Lee, Tomoko; Takeshima, Yasuhiro; Matsuo, Masafumi; Iijima, Kazumoto

    2017-11-01

    Duchenne and Becker muscular dystrophy (DMD/BMD) are caused by mutations in the dystrophin gene and are characterized by severe and mild progressive muscle wasting, respectively. Short stature has been reported as a feature of DMD in the Western hemisphere, but not yet confirmed in Orientals. Height of young BMD has not been fully characterized. Here, height of ambulant and steroid naive Japanese 179 DMD and 42 BMD patients between 4 and 10 years of age was retrospectively examined using height standard deviation score (SDS). The mean height SDS of DMD was -1.08 SD that was significantly smaller than normal (p < 0.001), indicating short stature of Japanese DMD. Furthermore, the mean height SDS of BMD was -0.27 SD, suggesting shorter stature than normal. Remarkably, the mean height SDS of DMD was significantly smaller than that of BMD (p < 0.0001). In DMD higher incidence of short stature (height SDS < -2.5 SD) was observed in Dp71 subgroup having mutations in dystrophin exons 63-79 than others having mutations in exons 1-62 (27.8% vs. 7.5%, p = 0.017). These suggested that height is influenced by dystrophin in not only DMD but also BMD and that dystrophin Dp71 has a role in height regulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Potency of high-intensity ultrasonic treatment for grain refinement of magnesium alloys

    International Nuclear Information System (INIS)

    Ramirez, A.; Qian Ma; Davis, B.; Wilks, T.; StJohn, D.H.

    2008-01-01

    High-intensity ultrasonic treatment (UT) for grain refinement of magnesium alloys has been investigated using a novel theoretical approach in order to better understand its grain-refining potential and the mechanism of nucleation. The process demonstrated significantly superior grain-refining potency to carbon inoculation for Al-containing magnesium alloys but inferior potency to zirconium for Al-free alloys. Details revealed by applying the theoretical approach to ultrasonic grain refinement provide new clues to understanding the mechanism of grain nucleation by UT

  19. A puzzle form of a non-verbal intelligence test gives significantly higher performance measures in children with severe intellectual disability.

    Science.gov (United States)

    Bello, Katrina D; Goharpey, Nahal; Crewther, Sheila G; Crewther, David P

    2008-08-01

    Assessment of 'potential intellectual ability' of children with severe intellectual disability (ID) is limited, as current tests designed for normal children do not maintain their interest. Thus a manual puzzle version of the Raven's Coloured Progressive Matrices (RCPM) was devised to appeal to the attentional and sensory preferences and language limitations of children with ID. It was hypothesized that performance on the book and manual puzzle forms would not differ for typically developing children but that children with ID would perform better on the puzzle form. The first study assessed the validity of this puzzle form of the RCPM for 76 typically developing children in a test-retest crossover design, with a 3 week interval between tests. A second study tested performance and completion rate for the puzzle form compared to the book form in a sample of 164 children with ID. In the first study, no significant difference was found between performance on the puzzle and book forms in typically developing children, irrespective of the order of completion. The second study demonstrated a significantly higher performance and completion rate for the puzzle form compared to the book form in the ID population. Similar performance on book and puzzle forms of the RCPM by typically developing children suggests that both forms measure the same construct. These findings suggest that the puzzle form does not require greater cognitive ability but demands sensory-motor attention and limits distraction in children with severe ID. Thus, we suggest the puzzle form of the RCPM is a more reliable measure of the non-verbal mentation of children with severe ID than the book form.

  20. Degree of Response to Homeopathic Potencies Correlates with Dipole Moment Size in Molecular Detectors: Implications for Understanding the Fundamental Nature of Serially Diluted and Succussed Solutions.

    Science.gov (United States)

    Cartwright, Steven J

    2018-02-01

     The use of solvatochromic dyes to investigate homeopathic potencies holds out the promise of understanding the nature of serially succussed and diluted solutions at a fundamental physicochemical level. Recent studies have shown that a range of different dyes interact with potencies and, moreover, the nature of the interaction is beginning to allow certain specific characteristics of potencies to be delineated.  The study reported in this article takes previous investigations further and aims to understand more about the nature of the interaction between potencies and solvatochromic dyes. To this end, the UV-visible spectra of a wide range of potential detectors of potencies have been examined using methodologies previously described.  Results presented demonstrate that solvatochromic dyes are a sub-group of a larger class of compounds capable of demonstrating interactions with potencies. In particular, amino acids containing an aromatic bridge also show marked optical changes in the presence of potencies. Several specific features of molecular detectors can now be shown to be necessary for significant interactions with homeopathic potencies. These include systems with a large dipole moment, electron delocalisation, polarizability and molecular rigidity.  Analysis of the optical changes occurring on interaction with potencies suggests that in all cases potencies increase the polarity of molecular detectors to a degree that correlates with the size of the compound's permanent or ground dipole moment. These results can be explained by inferring that potencies themselves have polarity. Possible candidates for the identity of potencies, based on these and previously reported results, are discussed. The Faculty of Homeopathy.

  1. Differential responses to cannabis potency: a typology of users based on self-reported consumption behaviour.

    Science.gov (United States)

    Korf, Dirk J; Benschop, Annemieke; Wouters, Marije

    2007-05-01

    To determine whether a classification of cannabis users into different types can help to clarify the relationship between cannabis potency and consumption behaviour, harmful physical effects and psychological dependency. A field sample of 388 respondents was recruited who had smoked cannabis at least once in the past month. They were contacted and interviewed in 28 cannabis coffee shops located in five Dutch cities. Data were collected with an assisted self-completion questionnaire. Cluster analysis was performed using the k-means method. Various ways were observed in which cannabis users in natural settings adjusted their intake to the potency of the drug. Cluster analysis identified three broad types of cannabis users. The strongest high type was the youngest, consumed the highest monthly dose, inhaled higher-potency cannabis more deeply, and scored highest on psychological cannabis dependency. The consistent high type preferred milder cannabis, consumed the lowest monthly dose, and compensated for stronger cannabis by inhaling less deeply and smoking less. The steady quantity type was the oldest, usually smoked alone, consumed an intermediate monthly dose, and did not tend to adjust the depth of inhalation to the potency of the cannabis. The results suggest that this typology might also reflect three successive stages in the careers of continuing cannabis users. Laboratory studies to assess the effects of higher THC concentrations on external and internal exposure to cannabis should allow for the possibility that the types of users studied can affect the results.

  2. Indexed effective orifice area is a significant predictor of higher mid- and long-term mortality rates following aortic valve replacement in patients with prosthesis-patient mismatch.

    Science.gov (United States)

    Chen, Jian; Lin, Yiyun; Kang, Bo; Wang, Zhinong

    2014-02-01

    Prosthesis-patient mismatch (PPM) is defined as a too-small effective orifice area (EOA) of an inserted prosthetic relative to body size, resulting in an abnormally high postoperative gradient. It is unclear, however, whether residual stenosis after aortic valve replacement (AVR) has a negative impact on mid- and long-term survivals. We searched electronic databases, including PubMed, Embase, Medline and the Cochrane controlled trials register, through October 2012, to identify published full-text English studies on the association between PPM and mortality rates. A significant PPM was defined as an indexed EOA (iEOA)<0.85 cm2/m2, and severe PPM as an iEOA<0.65 cm2/m2. Two reviewers independently assessed the studies for inclusion and extracted data. Fourteen observational studies, involving 14 874 patients, met our final inclusion criteria. Meta-analysis demonstrated that PPM significantly increased mid-term (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.19-1.69) and long-term (OR 1.52, 95% CI 1.26-1.84) all-cause mortalities. Subgroup analysis showed that PPM was associated with higher mid- and long-term mortality rates only in younger and predominantly female populations. Risk-adjusted sensitivity analysis showed that severe PPM was associated with reduced survival (adjusted hazard ratio [HR] 1.50, 95% CI 1.24-1.80), whereas moderate PPM was not (adjusted HR 0.96, 95% CI 0.86-1.07). Regardless of severity, however, PPM had a negative effect on survival in patients with impaired ejection fraction (adjusted HR 1.26, 95% CI 1.09-1.47). PPM (iEOA<0.85 cm2/m2) after AVR tended to be associated with increased long-term all-cause mortality in younger patients, females and patients with preoperative left ventricular dysfunction. Severe PPM (iEOA<0.65 cm2/m2) was a significant predictor of reduced long-term survival in all populations undergoing AVR.

  3. Variation in cannabis potency and prices in a newly legal market: evidence from 30 million cannabis sales in Washington state.

    Science.gov (United States)

    Smart, Rosanna; Caulkins, Jonathan P; Kilmer, Beau; Davenport, Steven; Midgette, Greg

    2017-12-01

    To (1) assess trends and variation in the market share of product types and potency sold in a legal cannabis retail market and (2) estimate how potency and purchase quantity influence price variation for cannabis flower. Secondary analysis of publicly available data from Washington State's cannabis traceability system spanning 7 July 2014 to 30 September 2016. Descriptive statistics and linear regressions assessed variation and trends in cannabis product variety and potency. Hedonic regressions estimated how purchase quantity and potency influence cannabis flower price variation. Washington State, USA. (1) A total of 44 482 176 million cannabis purchases, including (2) 31 052 123 cannabis flower purchases after trimming price and quantity outliers. Primary outcome measures were (1) monthly expenditures on cannabis, total delta-9-tetrahydrocannabinol (THC) concentration and cannabidiol (CBD) concentration by product type and (2) excise tax-inclusive price per gram of cannabis flower. Key covariates for the hedonic price regressions included quantity purchased, THC and CBD. Traditional cannabis flowers still account for the majority of spending (66.6%), but the market share of extracts for inhalation increased by 145.8% between October 2014 and September 2016, now comprising 21.2% of sales. The average THC-level for cannabis extracts is more than triple that for cannabis flowers (68.7% compared to 20.6%). For flower products, there is a statistically significant relationship between price per gram and both THC [coefficient = 0.012; 95% confidence interval (CI) = 0.011-0.013] and CBD (coefficient = 0.017; CI = 0.015-0.019). The estimated discount elasticity is -0.06 (CI = -0.07 to -0.05). In the state of Washington, USA, the legal cannabis market is currently dominated by high-THC cannabis flower, and features growing expenditures on extracts. For cannabis flower, both THC and CBD are associated with higher per-gram prices, and there are small but

  4. Conformational Flexibility Determines Selectivity and Antibacterial, Antiplasmodial, and Anticancer Potency of Cationic α-Helical Peptides*

    OpenAIRE

    Vermeer, Louic S.; Lan, Yun; Abbate, Vincenzo; Ruh, Emrah; Bui, Tam T.; Wilkinson, Louise J.; Kanno, Tokuwa; Jumagulova, Elmira; Kozlowska, Justyna; Patel, Jayneil; McIntyre, Caitlin A.; Yam, W. C.; Siu, Gilman; Atkinson, R. Andrew; Lam, Jenny K. W.

    2012-01-01

    Background: Antimicrobial peptides (AMPs) have the potential to act against multiple pathogenic targets. Results: AMPs that maintain conformational flexibility are more potent against multiple pathogens and less hemolytic. Conclusion: Antimicrobial action and hemolysis proceed via differing mechanisms. Significance: The potency, selectivity, and ability of AMPs to reach intracellular pathogens can be modulated using general principles.

  5. Antecendents and consequences of group potency : a study of self-managing teams in customer services

    NARCIS (Netherlands)

    Jong, de A.; Ruyter, de J.C.; Wetzels, M.G.M.

    2005-01-01

    This paper proposes and tests a model of antecedents and consequences of group potency in self-managing teams in retail banking. Based on data collected from boundary-spanning service employees organized in 60 teams and their customers, our findings reveal a significant positive impact of group

  6. 21 CFR 640.56 - Quality control test for potency.

    Science.gov (United States)

    2010-04-01

    ... quality control test for potency may be performed by a clinical laboratory which meets the standards of... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Quality control test for potency. 640.56 Section...) BIOLOGICS ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Cryoprecipitate § 640.56 Quality control...

  7. 21 CFR 660.25 - Potency tests without reference preparations.

    Science.gov (United States)

    2010-04-01

    ... recommended for slide tests or microplate techniques. Blood Grouping Reagent recommended for slide test... Grouping Reagent § 660.25 Potency tests without reference preparations. Products for which Reference Blood Grouping Reagents are not available shall be tested for potency by a method approved by the Director...

  8. Prion potency in stem cells biology.

    Science.gov (United States)

    Lopes, Marilene H; Santos, Tiago G

    2012-01-01

    Prion protein (PrP) can be considered a pivotal molecule because it interacts with several partners to perform a diverse range of critical biological functions that might differ in embryonic and adult cells. In recent years, there have been major advances in elucidating the putative role of PrP in the basic biology of stem cells in many different systems. Here, we review the evidence indicating that PrP is a key molecule involved in driving different aspects of the potency of embryonic and tissue-specific stem cells in self-perpetuation and differentiation in many cell types. It has been shown that PrP is involved in stem cell self-renewal, controlling pluripotency gene expression, proliferation, and neural and cardiomyocyte differentiation. PrP also has essential roles in distinct processes that regulate tissue-specific stem cell biology in nervous and hematopoietic systems and during muscle regeneration. Results from our own investigations have shown that PrP is able to modulate self-renewal and proliferation in neural stem cells, processes that are enhanced by PrP interactions with stress inducible protein 1 (STI1). Thus, the available data reveal the influence of PrP in acting upon the maintenance of pluripotent status or the differentiation of stem cells from the early embryogenesis through adulthood.

  9. The relationship between potency of oxidative stress and severity of dilated cardiomyopathy.

    Science.gov (United States)

    Demirbag, Recep; Yilmaz, Remzi; Erel, Ozcan; Gultekin, Unal; Asci, Durmus; Elbasan, Zafer

    2005-08-01

    It has been suggested that oxidative stress may have a role in the etiopathogenesis of congestive heart failure. To investigate and compare the oxidative-antioxidative status and oxidative stress index (OSI) of patients with idiopathic dilated cardiomyopathy (IDC) with those of healthy volunteers, and to determine the relationship between total antioxidant capacity (TAC) and ejection fraction (EF). Twenty-eight patients with IDC and 24 control subjects were enrolled in the study. Antioxidative status was evaluated by measuring the TAC and the vitamin C and thiol levels in the plasma. Oxidative status was evaluated by measuring the total peroxide level. The per cent ratio of TAC to total peroxide level was accepted as the OSI. EF was measured using Simpson's method. TAC and vitamin C and thiol levels of plasma were found to be significantly lower in patients with IDC than in control subjects (P total peroxide levels and OSIs were significantly higher in patients with IDC than in control subjects (P = 0.002 and P = 0.002, respectively). An important positive correlation was found between TAC and EF (r = 0.772; P total peroxide levels in patients. Oxidants are increased and antioxidants are decreased in patients with IDC; as a result, the oxidative-antioxidative balance is shifted to the oxidative side. There is a significant correlation between the potency of oxidative stress and the severity of IDC. It is believed that supplementation of antioxidants in the treatment of IDC may be helpful to these patients.

  10. Significance of the sexual openings and supplementary structures on the phylogeny of brachyuran crabs (Crustacea, Decapoda, Brachyura), with new nomina for higher-ranked podotreme taxa.

    Science.gov (United States)

    Guinot, Danièle; Tavares, Marcos; Castro, Peter

    2013-01-01

    The patterns of complexity of the male and female sexual openings in Brachyura, which have been the source of uncertainties and conflicting opinions, are documented, together with a study of the morphologies of the coxal and sternal gonopores in both sexes, penises, spermathecae, and gonopods. The vulvae, male gonopores and penises are described among selected taxa of Eubrachyura, and their function and evolution examined in the context of a wide variety of mating behaviours. The location of female and male gonopores, the condition of the penis (coxal and sternal openings and modalities of protection), and related configurations of thoracic sternites 7 and 8, which are modified by the intercalation of a wide sternal part (thoracic sternites 7 and 8) during carcinisation, show evidence of deep homology. They represent taxonomic criteria at all ranks of the family-series and may be used to test lineages. Of particular significance are the consequences of the posterior expansion of the thoracic sternum, which influences the condition, shape, and sclerotisation of the penis, and its emergence from coxal (heterotreme) to coxo-sternal, which is actually still coxal (heterotreme), in contrast to a sternal emergence (thoracotreme). The heterotreme-thoracotreme distinction results from two different trajectories of the vas deferens and its ejaculatory duct via the P5 coxa (Heterotremata) or through the thoracic sternum (Thoracotremata). Dissections of males of several families have demonstrated that this major difference not only affects the external surface (perforation of the coxa or the sternum by the ejaculatory duct) but also the internal anatomy. There is no evidence for an ejaculatory duct passing through the articular membrane between the P5 coxa and the thoracic sternum in any Brachyura, even when the sternal male gonopore is very close to the P5 coxa. Trends towards the coxo-sternal condition are exemplified by multistate characters, varying from a shallow

  11. The significance of recruiting underrepresented minorities in medicine: an examination of the need for effective approaches used in admissions by higher education institutions

    Directory of Open Access Journals (Sweden)

    Obed Figueroa

    2014-09-01

    Full Text Available The purpose of this paper is to examine the significance of recruiting underrepresented minorities in medicine (URM. This would include African Americans, Hispanics, and Native Americans. The research findings support the belief that URMs, upon graduating, are more likely to become practitioners in underserved communities, thereby becoming a resource that prompts us to find effective ways to help increase their college enrollments statewide. This paper analyzes the recruitment challenges for institutions, followed by a review of creative and effective approaches used by organizations and universities. The results have shown positive outcomes averaging a 50% increase in minority enrollments and retention. In other areas, such as cognitive development, modest gains were achieved in programs that were shorter in duration. The results nevertheless indicated steps in the right direction inspiring further program developments.

  12. An endogenous immune adjuvant released by necrotic cells for enhancement of DNA vaccine potency.

    Science.gov (United States)

    Dorostkar, Rohollah; Bamdad, Taravat; Parsania, Masoud; Pouriayevali, Hassan

    2012-12-01

    Improving vaccine potency in the induction of a strong cell-mediated cytotoxicity can enhance the efficacy of vaccines. Necrotic cells and the supernatant of necrotic tumor cells are attractive adjuvants, on account of their ability to recruit antigen-presenting cells to the site of antigen synthesis as well as its ability to stimulate the maturation of dendritic cells. To evaluate the utility of supernatant of necrotic tumor cells as a DNA vaccine adjuvant in a murine model. The supernatant of EL4 necrotic cells was co-administered with a DNA vaccine expressing the glycoprotein B of Herpes simplex virus-1 as an antigen model under the control of Cytomegalovirus promoter. C57BL/6 mice were vaccinated three times at two weeks intervals with glycoprotein B DNA vaccine and supernatant of necrotic EL4 cells. Five days after the last immunization, cell cytotoxicity, IFN-γ and IL-4 were evaluated. The obtained data showed that the production of IFN-γ from the splenocytes after antigenic stimulation in the presence of the supernatant of necrotic EL4 cells was significantly higher than the other groups (pEL4 cells in the mice immunized with DNA vaccine and supernatant of necrotic EL4 cells comparing to the other groups (p<0.001). The supernatant of necrotic cells contains adjuvant properties that can be considered as a candidate for tumor vaccination.

  13. PCR reveals significantly higher rates of Trypanosoma cruzi infection than microscopy in the Chagas vector, Triatoma infestans: High rates found in Chuquisaca, Bolivia

    Directory of Open Access Journals (Sweden)

    Lucero David E

    2007-06-01

    ' and TCZ2 (5' – CCT CCA AGC AGC GGA TAG TTC AGG – 3' primers. Amplicons were chromatographed on a 2% agarose gel with a 100 bp size standard, stained with ethidium bromide and viewed with UV fluorescence. For both the microscopy and PCR assays, we calculated sensitivity (number of positives by a method divided by the number of positives by either method and discrepancy (one method was negative and the other was positive at the locality, life stage and habitat level. The degree of agreement between PCR and microscopy was determined by calculating Kappa (k values with 95% confidence intervals. Results We observed a high prevalence of T. cruzi infection in T. infestans (81.16% by PCR and 56.52% by microscopy and discovered that PCR is significantly more sensitive than microscopic observation. The overall degree of agreement between the two methods was moderate (Kappa = 0.43 ± 0.07. The level of infection is significantly different among communities; however, prevalence was similar among habitats and life stages. Conclusion PCR was significantly more sensitive than microscopy in all habitats, developmental stages and localities in Chuquisaca, Bolivia. Overall we observed a high prevalence of T. cruzi infection in T. infestans in this area of Bolivia; however, microscopy underestimated infection at all levels examined.

  14. A new ELISA for determination of potency in snake antivenoms.

    Science.gov (United States)

    Rial, A; Morais, V; Rossi, S; Massaldi, H

    2006-09-15

    A competitive ELISA for potency determination of bothropic equine antivenom was developed and compared to the conventional in vivo ED(50) assay, with the aim of partially substituting the in vivo assay in the monitoring of antivenom immunoglobulin levels. On this purpose, blood samples were taken at different times during and after the immunization protocol of the lot of horses used for production of snake antivenom at the Instituto de Higiene, Uruguay. Both the competitive ELISA and the ED(50) assay were performed on those samples. In addition, a group of five commercial pepsin-digested antivenoms were tested by both methods. A significant (P<0.001) correlation (Pearson's r=0.957) was found between the ELISA titres and the corresponding ED(50) values, indicating that the in vitro test can estimate the neutralizing antibody capacity of the sera as well as the in vivo assay. By means of this new ELISA, it was found that the immunized animals maintained good venom antibody titres, in the order of 20-50% of the maximum achieved, even 10 month after the end of the immunization schedule. The main advantage of our ELISA design is its ability to correctly estimate the neutralization capacity of crude hyperimmune plasma and antivenom sera independently of their antibody composition in terms of whole IgG or F(ab')(2) fragment.

  15. Stereoselective potencies and relative toxicities of coniine enantiomers.

    Science.gov (United States)

    Lee, Stephen T; Green, Benedict T; Welch, Kevin D; Pfister, James A; Panter, Kip E

    2008-10-01

    Coniine, one of the major toxic alkaloids present in poison hemlock ( Conium maculatum), occurs in two optically active forms. A comparison of the relative potencies of (+)- and (-)-coniine enantiomers has not been previously reported. In this study, we separated the enantiomers of coniine and determined the biological activity of each enantiomer in vitro and in vivo. The relative potencies of these enantiomers on TE-671 cells expressing human fetal nicotinic neuromuscular receptors had the rank order of (-)-coniine > (+/-)-coniine > (+)-coniine. A mouse bioassay was used to determine the relative lethalities of (-)-, (+/-)-, and (+)-coniine in vivo. The LD 50 values of the coniine enantiomers were 7.0, 7.7, and 12.1 mg/kg for the (-)-, (+/-)-, and (+)- forms of coniine, respectively. The results from this study demonstrate that there is a stereoselective difference in the in vitro potencies of the enantiomers of coniine that directly correlates with the relative toxicities of the enantiomers in vivo.

  16. Roles of participation and feedback in group potency.

    Science.gov (United States)

    Gamero, Nuria; Peiró, José M; Zornoza, Ana; Picazo, Carmen

    2009-08-01

    The roles of group participation and group performance feedback were examined as antecedents of group potency, i.e., beliefs shared among a work group's members about the general effectiveness of the work group. Also examined were how group participation and the congruence of the feedback received from different sources about performance predicted convergence in members' beliefs about group effectiveness. The sample comprised 61 work groups of professionals involved in Master in Business Administration (MBA) programs (284 participants). Mean group size was 4.6 members (SD = .58). 65% of participants were male, and 51% were between 30 and 40 years of age. Data were gathered at two measurement times. Increases in group participation were positively related to increases in group potency and the convergence in beliefs about group effectiveness among group members over time. Results supported the premise that group performance feedback is an antecedent of changes in group potency over time.

  17. Correlation of initiating potency of skin carcinogens with potency to induce resistance to terminal differentiation in cultured mouse keratinocytes

    International Nuclear Information System (INIS)

    Kilkenny, A.E.; Morgan, D.; Spangler, E.F.; Yuspa, S.H.

    1985-01-01

    The induction by chemical carcinogens of resistance to terminal differentiation in cultured mouse keratinocytes has been proposed to represent a cellular change associated with the initiation phase of skin carcinogenesis. Previous results with this culture model indicated that the number of differentiation-resistant foci was correlated with the dose and known potency for several chemical carcinogens. Assay conditions were optimized to provide quantitative results for screening a variety of carcinogens for their potency as inducers of foci resistant to terminal differentiation. Eight skin initiators of varying potency and from different chemical classes and ultraviolet light were studied for their activity to induce this alteration in cultured epidermal cells from newborn BALB/c mice. There was an excellent positive correlation for the potency of these agents as initiators in vivo and as inducers of altered differentiation in vitro. The induction of resistant foci was independent of the relative cytotoxic effects of each agent except where cytotoxicity was extensive and reduced the number of foci. The results support the hypothesis that initiation of carcinogenesis in skin results in an alteration in the program of epidermal cell differentiation. The results also suggest that the assay is useful for identifying relative potency classes (strong, moderate, weak) of initiating agents

  18. Potency assay design for adjuvanted recombinant proteins as malaria vaccines.

    Science.gov (United States)

    Giersing, Birgitte K; Dubovsky, Filip; Saul, Allan; Denamur, Francoise; Minor, Philip; Meade, Bruce

    2006-05-15

    Many licensed vaccines are composed of live, attenuated or inactivated whole-cell microorganisms, or they comprise purified components from whole-cell extracts or culture supernatants. For some diseases, pathology is fairly well understood, and there may be known correlates of protection that provide obvious parameters for assessment of vaccine potency. However, this is not always the case, and some effective vaccines are routinely used even though the mechanisms or correlates of protection are unknown. Some more modern vaccine approaches employ purified recombinant proteins, based on molecules that appear on the surface of the pathogen. This is one of the strategies that has been adopted in the quest to develop a malaria vaccine. Use of these parasite antigens as vaccine candidates is supported by substantial epidemiological data, and some have demonstrated the ability to elicit protective responses in animal models of malaria infection. However, there is as yet no immunological correlate of protection and no functional assays or animal models that have demonstrated the ability to predict efficacy in humans. There is little precedence for the most appropriate and practical method for assessing potency of vaccines based on these recombinant molecules for malaria vaccines. This is likely because the majority of malaria vaccine candidates have only recently entered clinical evaluation. The PATH Malaria Vaccine Initiative (MVI) convened a panel with expertise in potency assay design from industry, governmental institutions, and regulatory bodies to discuss and review the rationale, available methods, and best approaches for assessing the potency of recombinant proteins, specifically for their use as malarial vaccines. The aim of this meeting was to produce a discussion document on the practical potency assessment of recombinant protein malaria vaccines, focusing on early phase potency assay development.

  19. Sexual potency following interactive ultrasound-guided brachytherapy for prostate cancer

    International Nuclear Information System (INIS)

    Stock, Richard G.; Stone, Nelson N.; Iannuzzi, Christopher

    1996-01-01

    Purpose: The effect of a therapeutic modality on sexual potency is often an important consideration for patients choosing a treatment for prostate cancer. We prospectively assessed patients' penile erectile function before and following interactive ultrasound-guided transperineal permanent radioactive seed implantation to determine its effect on sexual function. Methods and Materials: Eighty-nine patients underwent permanent radioactive seed implantation from June 1990 to April 1994 for localized prostate cancer (T1-T2) and were followed for a median of 15 months (1.5-52 months). 125 I seeds were implanted in 73 patients with a combined Gleason grade of 2-6, and 103 Pd seeds were implanted in 16 patients with higher grade lesions. The sexual potency of these patients was assessed prior to, at 3 and 6 months, and every 6 months after implantation. Erectile function was graded using a numerical score of 0 to 3 (0 = impotent (no erections), 1 = ability to have erections but insufficient for vaginal penetration, 2 = erectile function sufficient for vaginal penetration but suboptimal, 3 = normal erectile function). The pretreatment potency scores were as follows: 0 in 24 patients, 1 in 6 patients, 2 in 22 patients, and 3 in 37 patients. Results: The actuarial impotency rates (score = 0) following implantation for those patients possessing some degree of erectile function prior to implantation (65 patients) were 2.5% at 1 year and 6% at 2 years. The actuarial decrease in sexual function rates (a drop in score of at least one point) were 29% at 1 year and 39% at 2 years. Only two patients became impotent following treatment and this occurred at 1 year and 16 months. The time period for a decrease in erectile function to occur ranged from 1.8 months to 32.7 months, with a median of 6.8 months. Patients with higher grade tumors showed a greater decrease in potency score compared to patients with lower grade tumors. Conclusion: Interactive ultrasound-guided transperineal

  20. The comparative performance of the single intradermal test and the single intradermal comparative tuberculin test in Irish cattle, using tuberculin PPD combinations of differing potencies.

    Science.gov (United States)

    Good, M; Clegg, T A; Costello, E; More, S J

    2011-11-01

    In national bovine tuberculosis (BTB) control programmes, testing is generally conducted using a single source of bovine purified protein derivative (PPD) tuberculin. Alternative tuberculin sources should be identified as part of a broad risk management strategy as problems of supply or quality cannot be discounted. This study was conducted to compare the impact of different potencies of a single bovine PPD tuberculin on the field performance of the single intradermal comparative tuberculin test (SICTT) and single intradermal test (SIT). Three trial potencies of bovine PPD tuberculin, as assayed in naturally infected bovines, namely, low (1192IU/dose), normal (6184IU/dose) and high (12,554IU/dose) were used. Three SICTTs (using) were conducted on 2102 animals. Test results were compared based on reactor-status and changes in skin-thickness at the bovine tuberculin injection site. There was a significant difference in the number of reactors detected using the high and low potency tuberculins. In the SICTT, high and low potency tuberculin detected 40% more and 50% fewer reactors, respectively, than normal potency tuberculin. Furthermore, use of the low potency tuberculin in the SICTT failed to detect 20% of 35 animals with visible lesions, and in the SIT 11% of the visible lesion animals would have been classified as negative. Tuberculin potency is critical to the performance of both the SICTT and SIT. Tuberculin of different potencies will affect reactor disclosure rates, confounding between-year or between-country comparisons. Independent checks of tuberculin potency are an important aspect of quality control in national BTB control programmes. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. An Unusual Ligand Coordination Gives Rise to a New Family of Rhodium Metalloinsertors with Improved Selectivity and Potency

    Science.gov (United States)

    2015-01-01

    Rhodium metalloinsertors are octahedral complexes that bind DNA mismatches with high affinity and specificity and exhibit unique cell-selective cytotoxicity, targeting mismatch repair (MMR)-deficient cells over MMR-proficient cells. Here we describe a new generation of metalloinsertors with enhanced biological potency and selectivity, in which the complexes show Rh–O coordination. In particular, it has been found that both Δ- and Λ-[Rh(chrysi)(phen)(DPE)]2+ (where chrysi =5,6 chrysenequinone diimmine, phen =1,10-phenanthroline, and DPE = 1,1-di(pyridine-2-yl)ethan-1-ol) bind to DNA containing a single CC mismatch with similar affinities and without racemization. This is in direct contrast with previous metalloinsertors and suggests a possible different binding disposition for these complexes in the mismatch site. We ascribe this difference to the higher pKa of the coordinated immine of the chrysi ligand in these complexes, so that the complexes must insert into the DNA helix with the inserting ligand in a buckled orientation; spectroscopic studies in the presence and absence of DNA along with the crystal structure of the complex without DNA support this assignment. Remarkably, all members of this new family of compounds have significantly increased potency in a range of cellular assays; indeed, all are more potent than cisplatin and N-methyl-N′-nitro-nitrosoguanidine (MNNG, a common DNA-alkylating chemotherapeutic agent). Moreover, the activities of the new metalloinsertors are coupled with high levels of selective cytotoxicity for MMR-deficient versus proficient colorectal cancer cells. PMID:25254630

  2. Comparative reactivity of human IgE to cynomolgus monkey and human effector cells and effects on IgE effector cell potency

    Science.gov (United States)

    Saul, Louise; Saul, Louise; Josephs, Debra H; Josephs, Debra H; Cutler, Keith; Cutler, Keith; Bradwell, Andrew; Bradwell, Andrew; Karagiannis, Panagiotis; Karagiannis, Panagiotis; Selkirk, Chris; Selkirk, Chris; Gould, Hannah J; Gould, Hannah J; Jones, Paul; Jones, Paul; Spicer, James F; Spicer, James F; Karagiannis, Sophia N; Karagiannis, Sophia N

    2014-01-01

    Background: Due to genetic similarities with humans, primates of the macaque genus such as the cynomolgus monkey are often chosen as models for toxicology studies of antibody therapies. IgE therapeutics in development depend upon engagement with the FcεRI and FcεRII receptors on immune effector cells for their function. Only limited knowledge of the primate IgE immune system is available to inform the choice of models for mechanistic and safety evaluations.   Methods: The recognition of human IgE by peripheral blood lymphocytes from cynomolgus monkey and man was compared. We used effector cells from each species in ex vivo affinity, dose-response, antibody-receptor dissociation and potency assays. Results: We report cross-reactivity of human IgE Fc with cynomolgus monkey cells, and comparable binding kinetics to peripheral blood lymphocytes from both species. In competition and dissociation assays, however, human IgE dissociated faster from cynomolgus monkey compared with human effector cells. Differences in association and dissociation kinetics were reflected in effector cell potency assays of IgE-mediated target cell killing, with higher concentrations of human IgE needed to elicit effector response in the cynomolgus monkey system. Additionally, human IgE binding on immune effector cells yielded significantly different cytokine release profiles in each species. Conclusion: These data suggest that human IgE binds with different characteristics to human and cynomolgus monkey IgE effector cells. This is likely to affect the potency of IgE effector functions in these two species, and so has relevance for the selection of biologically-relevant model systems when designing pre-clinical toxicology and functional studies. PMID:24492303

  3. Phenolic acids significantly contribute to antioxidant potency of Gynostemma pentaphyllum aqueous and methanol extracts

    Czech Academy of Sciences Publication Activity Database

    Samec, D.; Valek-Zulj, L.; Martinez, S.; Grúz, Jiří; Piljac, A.; Piljac-Žegarac, J.

    2016-01-01

    Roč. 84, JUN (2016), s. 104-107 ISSN 0926-6690 R&D Projects: GA ČR GA14-34792S; GA MŠk(CZ) LO1204; GA MŠk LK21306 Institutional support: RVO:61389030 Keywords : Gynostemma pentaphyllum * Phenolic acids * Mass spectrometry Subject RIV: CE - Biochemistry Impact factor: 3.181, year: 2016

  4. High Throughput Combinatorial Formatting of PcrV Nanobodies for Efficient Potency Improvement*

    Science.gov (United States)

    De Tavernier, Evelyn; Detalle, Laurent; Morizzo, Erika; Roobrouck, Annelies; De Taeye, Severine; Rieger, Melanie; Verhaeghe, Tom; Correia, Andreia; Van Hegelsom, Rob; Figueirido, Rita; Noens, Jeroen; Steffensen, Søren; Stöhr, Thomas; Van de Velde, Willem; Depla, Erik; Dombrecht, Bruno

    2016-01-01

    Improving potencies through concomitant blockage of multiple epitopes and avid binding by fusing multiple (different) monovalent Nanobody building blocks via linker sequences into one multivalent polypeptide chain is an elegant alternative to affinity maturation. We explored a large and random formatting library of bivalent (combinations of two identical) and biparatopic (combinations of two different) Nanobodies for functional blockade of Pseudomonas aeruginosa PcrV. PcrV is an essential part of the P. aeruginosa type III secretion system (T3SS), and its oligomeric nature allows for multiple complex binding and blocking options. The library screening yielded a large number of promising biparatopic lead candidates, revealing significant (and non-trivial) preferences in terms of Nanobody building block and epitope bin combinations and orientations. Excellent potencies were confirmed upon further characterization in two different P. aeruginosa T3SS-mediated cytotoxicity assays. Three biparatopic Nanobodies were evaluated in a lethal mouse P. aeruginosa challenge pneumonia model, conferring 100% survival upon prophylactic administration and reducing lung P. aeruginosa burden by up to 2 logs. At very low doses, they protected the mice from P. aeruginosa infection-related changes in lung histology, myeloperoxidase production, and lung weight. Importantly, the most potent Nanobody still conferred protection after therapeutic administration up to 24 h post-infection. The concept of screening such formatting libraries for potency improvement is applicable to other targets and biological therapeutic platforms. PMID:27226529

  5. Potency trends of delta9-THC and other cannabinoids in confiscated marijuana from 1980-1997.

    Science.gov (United States)

    ElSohly, M A; Ross, S A; Mehmedic, Z; Arafat, R; Yi, B; Banahan, B F

    2000-01-01

    The analysis of 35,312 cannabis preparations confiscated in the USA over a period of 18 years for delta-9-tetrahydrocannabinol (delta9-THC) and other major cannabinoids is reported. Samples were identified as cannabis, hashish, or hash oil. Cannabis samples were further subdivided into marijuana (loose material, kilobricks and buds), sinsemilla, Thai sticks and ditchweed. The data showed that more than 82% of all confiscated samples were in the marijuana category for every year except 1980 (61%) and 1981 (75%). The potency (concentration of delta9-THC) of marijuana samples rose from less than 1.5% in 1980 to approximately 3.3% in 1983 and 1984, then fluctuated around 3% till 1992. Since 1992, the potency of confiscated marijuana samples has continuously risen, going from 3.1% in 1992 to 4.2% in 1997. The average concentration of delta9-THC in all cannabis samples showed a gradual rise from 3% in 1991 to 4.47% in 1997. Hashish and hash oil, on the other hand, showed no specific potency trends. Other major cannabinoids [cannabidiol (CBD), cannabinol (CBN), and cannabichromene (CBC)] showed no significant change in their concentration over the years.

  6. Assessment of the efficacies, potencies and bacteriological qualities ...

    African Journals Online (AJOL)

    The efficacies, potencies and qualities of these antibiotics were tested against some clinical isolates which include Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pyogenes in vitro. The overall mean zones of inhibition for the test organisms ranged from 33.0 ...

  7. The anaesthetic potency of benzocaine-hydrochloride in three ...

    African Journals Online (AJOL)

    The suitability of this substance in fish physiological research was assessed and it compared very favourably with MS 222 in inducing anaesthesia in freshwater fishes (Ferreira et al. 1979a). We have now compared the anaesthetic potency of four different concentrations of BH on three freshwater fish species at three ...

  8. Assessment of the insecticidal potency of neem ( Azadirachta Indica ...

    African Journals Online (AJOL)

    The potency of aqueous and methanolic extracts of neem (Azadirachta indica A. Juss) seed kernel, in inhibiting and disrupting development of Anopheles mosquito was assessed in the laboratory. Different concentrations of aqueous and methanolic extracts were tested on eggs, larvae and pupae. Both extracts were found ...

  9. Potency Studies of live- Attenuated Viral Vaccines Administered in ...

    African Journals Online (AJOL)

    We critically carried out a potency study in 1992 and 1997 on measles and poliovirus vaccines administered at five different vaccination centers in the metropolitan Lagos, Nigeria. using WHO guidelines on titration of live- viral vaccines, our results revealed that only 6 (16.7%) of 36 measles vaccine (MV) vials and 11 ...

  10. Steroselective Potencies and Relative Toxicities of Coniine Enantiomers

    Science.gov (United States)

    Coniine, one of the major toxic alkaloids present in poison hemlock (Conium maculatum), occurs in two optically active forms. A comparison of the relative potencies of (+)- and (-)-coniine enantiomers has not been previously reported. In this study, we separated the enantiomers of coniine and dete...

  11. Prediction of skin sensitization potency using machine learning approaches.

    Science.gov (United States)

    Zang, Qingda; Paris, Michael; Lehmann, David M; Bell, Shannon; Kleinstreuer, Nicole; Allen, David; Matheson, Joanna; Jacobs, Abigail; Casey, Warren; Strickland, Judy

    2017-07-01

    The replacement of animal use in testing for regulatory classification of skin sensitizers is a priority for US federal agencies that use data from such testing. Machine learning models that classify substances as sensitizers or non-sensitizers without using animal data have been developed and evaluated. Because some regulatory agencies require that sensitizers be further classified into potency categories, we developed statistical models to predict skin sensitization potency for murine local lymph node assay (LLNA) and human outcomes. Input variables for our models included six physicochemical properties and data from three non-animal test methods: direct peptide reactivity assay; human cell line activation test; and KeratinoSens™ assay. Models were built to predict three potency categories using four machine learning approaches and were validated using external test sets and leave-one-out cross-validation. A one-tiered strategy modeled all three categories of response together while a two-tiered strategy modeled sensitizer/non-sensitizer responses and then classified the sensitizers as strong or weak sensitizers. The two-tiered model using the support vector machine with all assay and physicochemical data inputs provided the best performance, yielding accuracy of 88% for prediction of LLNA outcomes (120 substances) and 81% for prediction of human test outcomes (87 substances). The best one-tiered model predicted LLNA outcomes with 78% accuracy and human outcomes with 75% accuracy. By comparison, the LLNA predicts human potency categories with 69% accuracy (60 of 87 substances correctly categorized). These results suggest that computational models using non-animal methods may provide valuable information for assessing skin sensitization potency. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Increasing vaccine potency through exosome antigen targeting.

    Science.gov (United States)

    Hartman, Zachary C; Wei, Junping; Glass, Oliver K; Guo, Hongtao; Lei, Gangjun; Yang, Xiao-Yi; Osada, Takuya; Hobeika, Amy; Delcayre, Alain; Le Pecq, Jean-Bernard; Morse, Michael A; Clay, Timothy M; Lyerly, Herbert K

    2011-11-21

    While many tumor associated antigens (TAAs) have been identified in human cancers, efforts to develop efficient TAA "cancer vaccines" using classical vaccine approaches have been largely ineffective. Recently, a process to specifically target proteins to exosomes has been established which takes advantage of the ability of the factor V like C1C2 domain of lactadherin to specifically address proteins to exosomes. Using this approach, we hypothesized that TAAs could be targeted to exosomes to potentially increase their immunogenicity, as exosomes have been demonstrated to traffic to antigen presenting cells (APC). To investigate this possibility, we created adenoviral vectors expressing the extracellular domain (ECD) of two non-mutated TAAs often found in tumors of cancer patients, carcinoembryonic antigen (CEA) and HER2, and coupled them to the C1C2 domain of lactadherin. We found that these C1C2 fusion proteins had enhanced expression in exosomes in vitro. We saw significant improvement in antigen specific immune responses to each of these antigens in naïve and tolerant transgenic animal models and could further demonstrate significantly enhanced therapeutic anti-tumor effects in a human HER2+ transgenic animal model. These findings demonstrate that the mode of secretion and trafficking can influence the immunogenicity of different human TAAs, and may explain the lack of immunogenicity of non-mutated TAAs found in cancer patients. They suggest that exosomal targeting could enhance future anti-tumor vaccination protocols. This targeting exosome process could also be adapted for the development of more potent vaccines in some viral and parasitic diseases where the classical vaccine approach has demonstrated limitations. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Can biochemistry drive drug discovery beyond simple potency measurements?

    Science.gov (United States)

    Chène, Patrick

    2012-04-01

    Among the fields of expertise required to develop drugs successfully, biochemistry holds a key position in drug discovery at the interface between chemistry, structural biology and cell biology. However, taking the example of protein kinases, it appears that biochemical assays are mostly used in the pharmaceutical industry to measure compound potency and/or selectivity. This limited use of biochemistry is surprising, given that detailed biochemical analyses are commonly used in academia to unravel molecular recognition processes. In this article, I show that biochemistry can provide invaluable information on the dynamics and energetics of compound-target interactions that cannot be obtained on the basis of potency measurements and structural data. Therefore, an extensive use of biochemistry in drug discovery could facilitate the identification and/or development of new drugs. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Comparative sensitizing potencies of fragrances, preservatives, and hair dyes

    DEFF Research Database (Denmark)

    Lidén, Carola; Yazar, Kerem; Johansen, Jeanne Duus

    2016-01-01

    the sensitizing potencies of fragrance substances, preservatives, and hair dye substances, which are skin sensitizers that frequently come into contact with the skin of consumers and workers, LLNA results and EC3 values for 72 fragrance substances, 25 preservatives and 107 hair dye substances were obtained from...... two published compilations of LLNA data and opinions by the Scientific Committee on Consumer Safety and its predecessors. The median EC3 values of fragrances (n = 61), preservatives (n = 19) and hair dyes (n = 59) were 5.9%, 0.9%, and 1.3%, respectively. The majority of sensitizing preservatives...... and hair dyes are thus strong or extreme sensitizers (EC3 value of ≤2%), and fragrances are mostly moderate sensitizers. Although fragrances are typically moderate sensitizers, they are among the most frequent causes of contact allergy. This indicates that factors other than potency need to be addressed...

  15. The effectivenes of science domain-based science learning integrated with local potency

    Science.gov (United States)

    Kurniawati, Arifah Putri; Prasetyo, Zuhdan Kun; Wilujeng, Insih; Suryadarma, I. Gusti Putu

    2017-08-01

    This research aimed to determine the significant effect of science domain-based science learning integrated with local potency toward science process skills. The research method used was a quasi-experimental design with nonequivalent control group design. The population of this research was all students of class VII SMP Negeri 1 Muntilan. The sample of this research was selected through cluster random sampling, namely class VII B as an experiment class (24 students) and class VII C as a control class (24 students). This research used a test instrument that was adapted from Agus Dwianto's research. The aspect of science process skills in this research was observation, classification, interpretation and communication. The analysis of data used the one factor anova at 0,05 significance level and normalized gain score. The significance level result of science process skills with one factor anova is 0,000. It shows that the significance level < alpha (0,05). It means that there was significant effect of science domain-based science learning integrated with local potency toward science learning process skills. The results of analysis show that the normalized gain score are 0,29 (low category) in control class and 0,67 (medium category) in experiment class.

  16. Progestin potency – Assessment and relevance to choice of oral contraceptives

    Directory of Open Access Journals (Sweden)

    Norman Goldstuck

    2011-12-01

    Conclusions: Newer progestins are more receptor selective and potency is less relevant than it was with older progestins. Epidemiological studies of progestin potency and its role in disease generally use out of date information. There is still confusion about the relationship of dose and potency in some studies. The use of the EPA can help eliminate this.

  17. Noise frame duration, masking potency and whiteness of temporal noise

    OpenAIRE

    Kukkonen, Helja; Rovamo, Jyrki; Donner, Kristian; Tammikallio, Marja; Raninen, Antii

    2002-01-01

    PURPOSE. Because of the limited contrast range, increasing the duration of the noise frame is often the only option for increasing the masking potency of external, white temporal noise. This, however, reduces the high-frequency cutoff beyond which noise is no longer white. This study was conducted to determine the longest noise frame duration that produces the strongest masking effect and still mimics white noise on the detection of sinusoidal flicker. \\ud \\ud METHODS. Contrast energy thresho...

  18. MAPPING OF SOIL DEGRADATION POTENCY IN PADDY FIELD WONOGIRI, INDONESIA

    Directory of Open Access Journals (Sweden)

    Mujiyo

    2016-06-01

    Full Text Available Sustainability of paddy field becomes the main concern as the media of biomass production, thus it is needed a datum and information about land characteristics to find out its degradation. Mapping of soil degradation potency in paddy field is an identification of initial soil condition to discover the land degradation potency. Mapping was done by overlaying map of soil, slope, rainfall and land use with standard procedures to obtain its value and status of soil degradation potency. Area mapping is an effective land for biomass production (natural forest, mixed farm, savanna, paddy field, shrub and dry field with approximately 43,291.00 hectares (ha in Sidoharjo, Girimarto, Jatipurno, Jatisrono, Jatiroto, Tirtomoyo, Nguntoronadi and Ngadirojo District. The result shows that soil degradation potency (SDP in Districts of Sidoharjo, Girimarto, Jatipurno, Jatisrono, Jatiroto, Tirtomoyo, Nguntoronadi and Ngadirojo are very low, low (DP II 20,702.47 ha (47.82%, moderate (DP III 15,823.80 ha (36,55% and high (DP IV 6,764.73 ha (15.63%. Paddy field covered 22,036.26 ha or about 50.90% of all area as effective biomass production, its SDP considers as low (DP II 16,021.04 ha (37.01% and moderate (DP III 6,015.22 ha (13,89%. Paddy field has a low SDP because it is commonly lies on flat area and conservation method by the farmer is maintaining the paddy bund and terrace. This study needs an advanced study to identify actual SDP through detail verification in the field, and also support by soil sample analysis in the laboratory.

  19. Relative potency estimation for synthetic petroleum skin carcinogens.

    OpenAIRE

    Holland, J M; Wolf, D A; Clark, B R

    1981-01-01

    A procedure for quantitative analysis of skin carcinogenesis data, for the purpose of establishing carcinogenic potency, has been applied to observations obtained from C3H mice exposed continuously to synthetic and natural petroleums. The importance of total polynuclear aromatic (PNA) content to the skin carcinogenic activity of the crude materials was also examined. Of three synthetic petroleums evaluated, all were shown capable of inducing skin neoplasms within a two-year exposure period. U...

  20. Formulation of Biocides Increases Antimicrobial Potency and Mitigates the Enrichment of Nonsusceptible Bacteria in Multispecies Biofilms

    Science.gov (United States)

    Forbes, Sarah; Cowley, Nicola; Mistry, Hitesh; Amézquita, Alejandro

    2017-01-01

    ABSTRACT The current investigation aimed to generate data to inform the development of risk assessments of biocide usage. Stabilized domestic drain biofilm microcosms were exposed daily over 6 months to increasing concentrations (0.01% to 1%) of the biocide benzalkonium chloride (BAC) in a simple aqueous solution (BAC-s) or in a complex formulation (BAC-f) representative of a domestic cleaning agent. Biofilms were analyzed by culture, differentiating by bacterial functional group and by BAC or antibiotic susceptibility. Bacterial isolates were identified by 16S rRNA sequencing, and changes in biofilm composition were assessed by high-throughput sequencing. Exposure to BAC-f resulted in significantly larger reductions in levels of viable bacteria than exposure to BAC-s, while bacterial diversity greatly decreased during exposure to both BAC-s and BAC-f, as evidenced by sequencing and viable counts. Increases in the abundance of bacteria exhibiting reduced antibiotic or BAC susceptibility following exposure to BAC at 0.1% were significantly greater for BAC-s than BAC-f. Bacteria with reduced BAC and antibiotic susceptibility were generally suppressed by higher BAC concentrations, and formulation significantly enhanced this effect. Significant decreases in the antimicrobial susceptibility of bacteria isolated from the systems before and after long-term BAC exposure were not detected. In summary, dose-dependent suppression of bacterial viability by BAC was enhanced by formulation. Biocide exposure decreased bacterial diversity and transiently enriched populations of organisms with lower antimicrobial susceptibility, and the effects were subsequently suppressed by exposure to 1% BAC-f, the concentration most closely reflecting deployment in formulated products. IMPORTANCE Assessment of the risks of biocide use has been based mainly on the exposure of axenic cultures of bacteria to biocides in simple aqueous solutions. The current investigation aimed to assess the

  1. Regulatory T cell suppressive potency dictates the balance between bacterial proliferation and clearance during persistent Salmonella infection.

    Directory of Open Access Journals (Sweden)

    Tanner M Johanns

    2010-08-01

    Full Text Available The pathogenesis of persistent infection is dictated by the balance between opposing immune activation and suppression signals. Herein, virulent Salmonella was used to explore the role and potential importance of Foxp3-expressing regulatory T cells in dictating the natural progression of persistent bacterial infection. Two distinct phases of persistent Salmonella infection are identified. In the first 3-4 weeks after infection, progressively increasing bacterial burden was associated with delayed effector T cell activation. Reciprocally, at later time points after infection, reductions in bacterial burden were associated with robust effector T cell activation. Using Foxp3(GFP reporter mice for ex vivo isolation of regulatory T cells, we demonstrate that the dichotomy in infection tempo between early and late time points is directly paralleled by drastic changes in Foxp3(+ Treg suppressive potency. In complementary experiments using Foxp3(DTR mice, the significance of these shifts in Treg suppressive potency on infection outcome was verified by enumerating the relative impacts of regulatory T cell ablation on bacterial burden and effector T cell activation at early and late time points during persistent Salmonella infection. Moreover, Treg expression of CTLA-4 directly paralleled changes in suppressive potency, and the relative effects of Treg ablation could be largely recapitulated by CTLA-4 in vivo blockade. Together, these results demonstrate that dynamic regulation of Treg suppressive potency dictates the course of persistent bacterial infection.

  2. A novel antilithiatic protein from Tribulus terrestris having cytoprotective potency.

    Science.gov (United States)

    Aggarwal, Anshu; Tandon, Simran; Singla, Surinder Kumar; Tandon, Chanderdeep

    2012-08-01

    Adhesion of calcium oxalate (CaOx) crystals to kidney cells is a key event in kidney stones associated with marked hyperoxaluria. As the propensity of stone recurrence and persistent side effects are not altered by surgical techniques available, phytotherapeutic agents could be useful as an adjuvant therapy. The present study is aimed at examining the antilithiatic potency of the protein biomolecules of Tribulus terrestris, a plant which is a common constituent of herbal marketed preparations to treat urolithiasis. Various biochemical methods with mass spectrometry were used to purify and characterize the purified protein. The protective potency of the protein was tested on the oxalate induced injury on renal epithelial cell lines (NRK 52E). An antilithiatic protein having molecular weight of ~ 60kDa was purified. This purified protein showed similarities with Carotenoid cleavage dioxygenase 7 (CCD7) of Arabidopsis thaliana after matching peptide mass fingerprints in MASCOT search engine. An EF hand domain was identified in CCD7 by SCAN PROSITE. Presence of an EF hand domain, a characteristic feature of calcium binding proteins and a role in the synthesis of retinol which is transported by retinol binding protein, a protein found in kidney stone matrix; of CCD7 support the role of TTP as an antilithiatic protein. The protective potency of TTP on NRK 52E was quite comparable to the aqueous extract of cystone. Our findings suggest that this purified protein biomolecule from Tribulus terrestris could open new vista in medical management of urolithiasis.

  3. Potential application of the consistency approach for vaccine potency testing.

    Science.gov (United States)

    Arciniega, J; Sirota, L A

    2012-01-01

    The Consistency Approach offers the possibility of reducing the number of animals used for a potency test. However, it is critical to assess the effect that such reduction may have on assay performance. Consistency of production, sometimes referred to as consistency of manufacture or manufacturing, is an old concept implicit in regulation, which aims to ensure the uninterrupted release of safe and effective products. Consistency of manufacture can be described in terms of process capability, or the ability of a process to produce output within specification limits. For example, the standard method for potency testing of inactivated rabies vaccines is a multiple-dilution vaccination challenge test in mice that gives a quantitative, although highly variable estimate. On the other hand, a single-dilution test that does not give a quantitative estimate, but rather shows if the vaccine meets the specification has been proposed. This simplified test can lead to a considerable reduction in the number of animals used. However, traditional indices of process capability assume that the output population (potency values) is normally distributed, which clearly is not the case for the simplified approach. Appropriate computation of capability indices for the latter case will require special statistical considerations.

  4. Trypsin diminishes the rat potency of polio serotype 3.

    Science.gov (United States)

    ten Have, R; Westdijk, J; Levels, L M A R; Koedam, P; de Haan, A; Hamzink, M R J; Metz, B; Kersten, G F A

    2015-11-01

    This study addresses observations made in view of testing in practice the guideline in the European Pharmacopoeia (EP) on omitting the rat potency test for release of polio containing vaccines. In general, use of the guideline is valid and the D-antigen ELISA can indeed be used as an in vitro alternative for the in vivo test. However, the set-up of the ELISA is crucial and should include detection of antigenic site 1 in polio serotype 3 as destruction of that site by trypsin results in a reduced rat potency. Antigenic site 1 in polio serotype 2 may also be modified by trypsin, but the cleavage of viral protein 1 (VP1) did not affect the rat potency. Therefore, any antigenic site, except site 1, can be used for detection of polio serotype 2. It is advised to include testing of the effect of trypsin treatment in the EP-guideline. This allows polio vaccine manufacturers to check whether their in-house ELISA needs improvement. Copyright © 2015 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  5. The solidarization potencies of Buddhist axiological system and humanistic grounding of its priorities

    Directory of Open Access Journals (Sweden)

    Stefaniv Maryana Ivanivna

    2016-10-01

    Full Text Available The article is devoted to the analysis of the value system of the Buddhist religion in the context of current globalization trends. The author considers the stereotypes about the confrontation in the parameters “West – East” and offers the alternative view on the model of Buddhist values and its solidarization potencies. The author extrapolates her ideas on the intellectual and practical sense of a famous Buddhist philosopher Daisaku Ikeda. The author emphasizes the importance of a practical way of aesthetic and ethical projects initiated by Ikeda and justifies their humanistic social significance.

  6. Homeopathic Individualized Q-Potencies versus Fluoxetine for Moderate to Severe Depression: Double-Blind, Randomized Non-Inferiority Trial

    Directory of Open Access Journals (Sweden)

    U. C. Adler

    2011-01-01

    Full Text Available Homeopathy is a complementary and integrative medicine used in depression, The aim of this study is to investigate the non-inferiority and tolerability of individualized homeopathic medicines [Quinquagintamillesmial (Q-potencies] in acute depression, using fluoxetine as active control. Ninety-one outpatients with moderate to severe depression were assigned to receive an individualized homeopathic medicine or fluoxetine 20 mg day−1 (up to 40 mg day−1 in a prospective, randomized, double-blind double-dummy 8-week, single-center trial. Primary efficacy measure was the analysis of the mean change in the Montgomery & Åsberg Depression Rating Scale (MADRS depression scores, using a non-inferiority test with margin of 1.45. Secondary efficacy outcomes were response and remission rates. Tolerability was assessed with the side effect rating scale of the Scandinavian Society of Psychopharmacology. Mean MADRS scores differences were not significant at the 4th (P = .654 and 8th weeks (P = .965 of treatment. Non-inferiority of homeopathy was indicated because the upper limit of the confidence interval (CI for mean difference in MADRS change was less than the non-inferiority margin: mean differences (homeopathy-fluoxetine were −3.04 (95% CI −6.95, 0.86 and −2.4 (95% CI −6.05, 0.77 at 4th and 8th week, respectively. There were no significant differences between the percentages of response or remission rates in both groups. Tolerability: there were no significant differences between the side effects rates, although a higher percentage of patients treated with fluoxetine reported troublesome side effects and there was a trend toward greater treatment interruption for adverse effects in the fluoxetine group. This study illustrates the feasibility of randomized controlled double-blind trials of homeopathy in depression and indicates the non-inferiority of individualized homeopathic Q-potencies as compared to fluoxetine in acute treatment of

  7. Homeopathic Individualized Q-Potencies versus Fluoxetine for Moderate to Severe Depression: Double-Blind, Randomized Non-Inferiority Trial

    Science.gov (United States)

    Adler, U. C.; Paiva, N. M. P.; Cesar, A. T.; Adler, M. S.; Molina, A.; Padula, A. E.; Calil, H. M.

    2011-01-01

    Homeopathy is a complementary and integrative medicine used in depression, The aim of this study is to investigate the non-inferiority and tolerability of individualized homeopathic medicines [Quinquagintamillesmial (Q-potencies)] in acute depression, using fluoxetine as active control. Ninety-one outpatients with moderate to severe depression were assigned to receive an individualized homeopathic medicine or fluoxetine 20 mg day−1 (up to 40 mg day−1) in a prospective, randomized, double-blind double-dummy 8-week, single-center trial. Primary efficacy measure was the analysis of the mean change in the Montgomery & Åsberg Depression Rating Scale (MADRS) depression scores, using a non-inferiority test with margin of 1.45. Secondary efficacy outcomes were response and remission rates. Tolerability was assessed with the side effect rating scale of the Scandinavian Society of Psychopharmacology. Mean MADRS scores differences were not significant at the 4th (P = .654) and 8th weeks (P = .965) of treatment. Non-inferiority of homeopathy was indicated because the upper limit of the confidence interval (CI) for mean difference in MADRS change was less than the non-inferiority margin: mean differences (homeopathy-fluoxetine) were −3.04 (95% CI −6.95, 0.86) and −2.4 (95% CI −6.05, 0.77) at 4th and 8th week, respectively. There were no significant differences between the percentages of response or remission rates in both groups. Tolerability: there were no significant differences between the side effects rates, although a higher percentage of patients treated with fluoxetine reported troublesome side effects and there was a trend toward greater treatment interruption for adverse effects in the fluoxetine group. This study illustrates the feasibility of randomized controlled double-blind trials of homeopathy in depression and indicates the non-inferiority of individualized homeopathic Q-potencies as compared to fluoxetine in acute treatment of outpatients

  8. Assessment of the analgesic potency of constant rate infusion of ...

    African Journals Online (AJOL)

    Parameters determined were heart and respiratory rates, blood glucose level, pain score and body weight. Results showed that mean heart rate, respiratory rate and body weight were not differed significantly (p > 0.05) within and among the groups. Mean blood glucose level of group 4 was significantly higher (p < 0.05) ...

  9. In vivo potency revisited - Keep the target in sight.

    Science.gov (United States)

    Gabrielsson, Johan; Peletier, Lambertus A; Hjorth, Stephan

    2018-04-01

    Potency is a central parameter in pharmacological and biochemical sciences, as well as in drug discovery and development endeavors. It is however typically defined in terms only of ligand to target binding affinity also in in vivo experimentation, thus in a manner analogous to in in vitro studies. As in vivo potency is in fact a conglomerate of events involving ligand, target, and target-ligand complex processes, overlooking some of the fundamental differences between in vivo and in vitro may result in serious mispredictions of in vivo efficacious dose and exposure. The analysis presented in this paper compares potency measures derived from three model situations. Model A represents the closed in vitro system, defining target binding of a ligand when total target and ligand concentrations remain static and constant. Model B describes an open in vivo system with ligand input and clearance (Cl (L) ), adding in parallel to the turnover (k syn , k deg ) of the target. Model C further adds to the open in vivo system in Model B also the elimination of the target-ligand complex (k e(RL) ) via a first-order process. We formulate corresponding equations of the equilibrium (steady-state) relationships between target and ligand, and complex and ligand for each of the three model systems and graphically illustrate the resulting simulations. These equilibrium relationships demonstrate the relative impact of target and target-ligand complex turnover, and are easier to interpret than the more commonly used ligand-, target- and complex concentration-time courses. A new potency expression, labeled L 50 , is then derived. L 50 is the ligand concentration at half-maximal target and complex concentrations and is an amalgamation of target turnover, target-ligand binding and complex elimination parameters estimated from concentration-time data. L 50 is then compared to the dissociation constant K d (target-ligand binding affinity), the conventional Black & Leff potency estimate EC 50

  10. Vasorelaxant potencies and receptor binding affinities of atrial natriuretic hormone (ANH) analogues

    International Nuclear Information System (INIS)

    Bush, E.N.; Green, E.M.; Artman, L.D.; Devine, E.M.; Sarin, V.; Rockway, T.W.; Connolly, P.J.; Kiso, Y.; Holleman, W.H.

    1986-01-01

    ANH (1-28) (α-rat ANP) produces hypotensive effects in vivo, presumably via interaction with specific receptors. Vasorelaxant potencies (pD 2 ) and intrinsic activities of ANH analogues were measured in histamine constricted rabbit aorta rings. Binding affinities (K/sub I/) of the compounds were studied in rabbit aorta renal cortex and adrenal, using the radio-ligand 125 I-Tyr 28 -ANH (1-28). Significant correlations (r 2 s in aorta, and the log D/sub I/s in each of the three tissues were observed for the following cyclic compounds, listed in order of potency: ANH (1-28) greater than or equal to ANH (6-28) greater than or equal to Met 12 -ANH (1-28) (α-human ANP) greater than or equal to cyclohexyl-Ala (Cha) 8 -ANH (5-28) > Lys 11 -ANH (5-28) = ANH (5-28) (atriopeptin III) = ANH (5-27) (atriopeptin II) = Cha 21 -ANH (5-28) greater than or equal to ANH (7-28) > Cha 15 -ANH (5-28) = Pro 10 -ANH (5-28) = ANH (5-25) (atriopeptin I) = Asn 13 -ANH (5-28) = Tyr 9 -ANH (5-28) > des-Gly 9 -ANH (5-28) > ANH (7-23) = Pro 10 -ANH (7-23) greater than or equal to (D)Ala 9 -ANH (7-23) > Pro 9 -ANH (7-13). In summary, the affinities of several ANH analogues for both vascular and nonvascular receptors agree with their vasorelaxant potencies

  11. Effects of Pomegranate Seed Oil on the Fertilization Potency of Rat's Sperm.

    Science.gov (United States)

    Nikseresht, Mohsen; Fallahzadeh, Ali Reza; Toori, Mehdi Akbartabar; Mahmoudi, Reza

    2015-12-01

    Pomegranate has been taken great scientific attention in recent years due to its health benefits. Pomegranate seed oil is a rich source of 9-cis, and 11-trans conjugate linolenic acid. The aim of this study was to evaluate the effect of dietary pomegranate seed oil on the fertilization potency of rat's sperm. Twenty-four male Wistar rats were divided into four groups. The first group, which served as the control group, received 1 mL of corn oil for seven weeks. Groups II, III, IV served as the experimental groups received 200, 500 and 1000 mg/kg of pomegranate seed oil, for the same period of time respectively. After seven weeks, all of the rats were sacrificed, and their epididymis sperm was collected and added to IVF medium (T6) containing metaphase II oocytes. Almost 21 oocytes had been removed from every female rat oviduct. In this medium, oocyte fertilization, cleavage rates, and embryo development into blastocysts, were evaluated by inverted microscopy. Levels of LD50 in the oral route in male rats were more than 5000 mg/kg body weight. Our data showed that the rates of fertilization, cleavage and embryo development into blastocysts were higher in the groups that had received 500 and 1000 mg/kg body weight of pomegranate seed oil. This study demonstrated that pomegranate seed oil had a positive effect on the fertilization potency of male rats. These beneficial effects may be useful in assisted reproductive technology.

  12. Analysis of potency and development of renewable energy based on agricultural biomass waste in Jambi province

    Science.gov (United States)

    Devita, W. H.; Fauzi, A. M.; Purwanto, Y. A.

    2018-05-01

    Indonesia has the big potency of biomass. The source of biomass energy is scattered all over the country. The big potential in concentrated scale is on the island of Sumatera. Jambi province which is located in Sumatra Island has the potency of biomass energy due to a huge area for estate crop and agriculture. The Indonesian government had issued several policies which put a higher priority on the utilization of renewable energy. This study aimed to identify the conditions and distribution of biomass waste potential in Jambi province. The potential biomass waste in Jambi province was 27,407,183 tons per year which dominated of oil palm residue (46.16%), rice husk and straw (3.52%), replanting rubberwood (50.32%). The total power generated from biomass waste was 129 GWhth per year which is consisted of palm oil residue (56 GWhth per year), rice husk and straw (3.22 GWhth per year), rubberwood (70.56 GWhth per year). Based on the potential of biomass waste, then the province of Jambi could obtain supplies of renewable energy from waste biomass with electricity generated amount to 32.34 GWhe per year.

  13. Enterocin A mutants identified by saturation mutagenesis enhance potency towards vancomycin-resistant Enterococci.

    Science.gov (United States)

    McClintock, Maria K; Kaznessis, Yiannis N; Hackel, Benjamin J

    2016-02-01

    Vancomycin-resistant Enterococci infections are a significant clinical problem. One proposed solution is to use probiotics, such as lactic acid bacteria, to produce antimicrobial peptides at the site of infection. Enterocin A, a class 2a bacteriocin, exhibits inhibitory activity against E. faecium and E. faecalis, which account for 86% of vancomycin-resistant Enterococci infections. In this study, we aimed to engineer enterocin A mutants with enhanced potency within a lactic acid bacterial production system. Peptide mutants resulting from saturation mutagenesis at sites A24 and T27 were efficiently screened in a 96-well plate assay for inhibition of pathogen growth. Several mutants exhibit increased potency relative to wild-type enterocin A in both liquid- and solid-medium growth assays. In particular, A24P and T27G exhibit enhanced inhibition of multiple strains of E. faecium and E. faecalis, including clinically isolated vancomycin-resistant strains. A24P and T27G enhance killing of E. faecium 8 by 13 ± 3- and 18 ± 4-fold, respectively. The engineered enterocin A/lactic acid bacteria systems offer significant potential to combat antibiotic-resistant infections. © 2015 Wiley Periodicals, Inc.

  14. Potency of delta 9-THC and other cannabinoids in cannabis in England in 2005: implications for psychoactivity and pharmacology.

    Science.gov (United States)

    Potter, David J; Clark, Peter; Brown, Marc B

    2008-01-01

    Gas chromatography was used to study the cannabinoid content ("potency") of illicit cannabis seized by police in England in 2004/5. Of the four hundred and fifty two samples, indoor-grown unpollinated female cannabis ("sinsemilla") was the most frequent form, followed by resin (hashish) and imported outdoor-grown herbal cannabis (marijuana). The content of the psychoactive cannabinoid delta 9-tetrahydrocannabinol (THC) varied widely. The median THC content of herbal cannabis and resin was 2.1% and 3.5%, respectively. The median 13.9% THC content of sinsemilla was significantly higher than that recorded in the UK in 1996/8. In sinsemilla and imported herbal cannabis, the content of the antipsychotic cannabinoid cannabidiol (CBD) was extremely low. In resin, however, the average CBD content exceeded that of THC, and the relative proportions of the two cannabinoids varied widely between samples. The increases in average THC content and relative popularity of sinsemilla cannabis, combined with the absence of the anti-psychotic cannabinoid CBD, suggest that the current trends in cannabis use pose an increasing risk to those users susceptible to the harmful psychological effects associated with high doses of THC.

  15. Establishing criteria for human mesenchymal stem cell potency.

    Science.gov (United States)

    Samsonraj, Rebekah M; Rai, Bina; Sathiyanathan, Padmapriya; Puan, Kia Joo; Rötzschke, Olaf; Hui, James H; Raghunath, Michael; Stanton, Lawrence W; Nurcombe, Victor; Cool, Simon M

    2015-06-01

    This study sought to identify critical determinants of mesenchymal stem cell (MSC) potency using in vitro and in vivo attributes of cells isolated from the bone marrow of age- and sex-matched donors. Adherence to plastic was not indicative of potency, yet capacity for long-term expansion in vitro varied considerably between donors, allowing the grouping of MSCs from the donors into either those with high-growth capacity or low-growth capacity. Using this grouping strategy, high-growth capacity MSCs were smaller in size, had greater colony-forming efficiency, and had longer telomeres. Cell-surface biomarker analysis revealed that the International Society for Cellular Therapy (ISCT) criteria did not distinguish between high-growth capacity and low-growth capacity MSCs, whereas STRO-1 and platelet-derived growth factor receptor alpha were preferentially expressed on high-growth capacity MSCs. These cells also had the highest mean expression of the mRNA transcripts TWIST-1 and DERMO-1. Irrespective of these differences, both groups of donor MSCs produced similar levels of key growth factors and cytokines involved in tissue regeneration and were capable of multilineage differentiation. However, high-growth capacity MSCs produced approximately double the volume of mineralized tissue compared to low-growth capacity MSCs when assessed for ectopic bone-forming ability. The additional phenotypic criteria presented in this study when combined with the existing ISCT minimum criteria and working proposal will permit an improved assessment of MSC potency and provide a basis for establishing the quality of MSCs prior to their therapeutic application. © 2015 AlphaMed Press.

  16. Potency of Microalgae as Biodiesel Source in Indonesia

    Directory of Open Access Journals (Sweden)

    H Hadiyanto

    2012-04-01

    Full Text Available Within 20 years, Indonesia should find another energy alternative to substitutecurrent fossil oil. Current use of renewable energy is only 5% and need to be improved up to 17%of our energy mix program. Even though, most of the area in Indonesia is covered by sea, howeverthe utilization of microalgae as biofuel production is still limited. The biodiesel from currentsources (Jatropha, palm oil, and sorghum is still not able to cover all the needs if the fossil oilcannot be explored anymore. In this paper, the potency of microalgae in Indonesia was analysed asthe new potential of energy (biodiesel sources.

  17. Potency of Microalgae as Biodiesel Source in Indonesia

    Directory of Open Access Journals (Sweden)

    H Hadiyanto

    2012-02-01

    Full Text Available Within 20 years, Indonesia should find another energy alternative to substitute current fossil oil. Current use of renewable energy is only 5% and need to be improved up to 17% of our energy mix program. Even though, most of the area in Indonesia is covered by sea, however the utilization of microalgae as biofuel production is still limited. The biodiesel from current sources (Jatropha, palm oil, and sorghum is still not able to cover all the needs if the fossil oil cannot be explored anymore. In this paper, the potency of microalgae in Indonesia was analysed as the new potential of energy (biodiesel sources.

  18. Cannabis-induced psychosis associated with high potency "wax dabs".

    Science.gov (United States)

    Pierre, Joseph M; Gandal, Michael; Son, Maya

    2016-04-01

    With mounting evidence that the risk of cannabis-induced psychosis may be related to both dose and potency of tetrahydrocannbinol (THC), increasing reports of psychosis associated with cannabinoids containing greater amounts of THC are anticipated. We report two cases of emergent psychosis after using a concentrated THC extract known as cannabis "wax," "oil," or "dabs" raising serious concerns about its psychotic liability. Although "dabbing" with cannabis wax is becoming increasingly popular in the US for both recreational and "medicinal" intentions, our cases raise serious concerns about its psychotic liability and highlight the importance of understanding this risk by physicians recommending cannabinoids for purported medicinal purposes. Published by Elsevier B.V.

  19. PROBIOTIC POTENCY OF LACTOBACILLUS SPP. ISOLATED FROM SUMBAWA MARE MILK

    Directory of Open Access Journals (Sweden)

    I Nengah Sujaya

    2008-03-01

    Full Text Available This research was deigned to elucidate the potency of Lactobacillus spp. isolated from sumbawa mare milk to be developed as a probiotic. Sixteen lacobacilli were screened based on their resitancy to a model of gastric juice at pH 2, 3, and 4, then followed by their resistncy to small intestional fluid model containing deoxycholic. Three lactobacilli i.e. Lactobacillus sp. SKA13, Lactobacillus rhamnosus SKG34 and Lactobacillus rhamnosus SKG49 were found to be resistentent to gastric juice at pH 3 and 4. However, there were no lactobacilli resisted to pH 2. Lactobacillus rhamnosus SKG34 and Lactobacillus rhamnosus SKG49 were able to reach the colon even after being expossed to a model of intestinal fluid containing 0,4 mM deoxycholate and pancreatine. Therefore, these isolates have a potency to be developed as probiotic lactobacilli. Nevertherless, these lactobcailli could probably transform cholic acid into secondary bile acids, which were not expected to be found in the probiotic, and this capability is not appropriate for probiotic. This character is worthly to be studied since it has never been reported in lactobacilli.

  20. Estimating skin sensitization potency from a single dose LLNA.

    Science.gov (United States)

    Roberts, David W

    2015-04-01

    Skin sensitization is an important aspect of safety assessment. The mouse local lymph node assay (LLNA) developed in the 1990 s is an in vivo test used for skin sensitization hazard identification and characterization. More recently a reduced version of the LLNA (rLLNA) has been developed as a means of identifying, but not quantifying, sensitization hazard. The work presented here is aimed at enabling rLLNA data to be used to give quantitative potency information that can be used, inter alia, in modeling and read-across approaches to non-animal based potency estimation. A probit function has been derived enabling estimation of EC3 from a single dose. This has led to development of a modified version of the rLLNA, whereby as a general principle the SI value at 10%, or at a lower concentration if 10% is not testable, is used to calculate the EC3. This version of the rLLNA has been evaluated against a selection of chemicals for which full LLNA data are available, and has been shown to give EC3 values in good agreement with those derived from the full LLNA. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Agmatine enhances antidepressant potency of MK-801 and conventional antidepressants in mice.

    Science.gov (United States)

    Neis, Vivian Binder; Moretti, Morgana; Manosso, Luana Meller; Lopes, Mark W; Leal, Rodrigo Bainy; Rodrigues, Ana Lúcia S

    2015-03-01

    Agmatine, an endogenous guanidine amine, has been shown to produce antidepressant-like effects in animal studies. This study investigated the effects of the combined administration of agmatine with either conventional monoaminergic antidepressants or the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 in the tail suspension test (TST) in mice. The aim was to evaluate the extent of the antidepressant synergism by examining the ability of a fixed dose of agmatine to shift the antidepressant potency of fluoxetine, imipramine, bupropion and MK-801. A sub-effective dose of agmatine (0.0001 mg/kg, p.o.) significantly increased the potency by which fluoxetine, imipramine, bupropion and MK-801 decreased immobility time in the TST by 2-fold (fluoxetine), 10-fold (imipramine and bupropion) and 100-fold (MK-801). Combined with previous evidence indicating a role of monoaminergic systems in the effect of agmatine, the current data suggest that agmatine may modulate monoaminergic neurotransmission and augment the activity of conventional antidepressants. Moreover, this study found that agmatine substantially augmented the antidepressant-like effect of MK-801, reinforcing the notion that this compound modulates NMDA receptor activation. These preclinical data may stimulate future clinical studies testing the effects of augmentation therapy with agmatine for the management of depressive disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Antibiotic Potency against E. coli Is Enhanced by Channel-Forming Alkyl Lariat Ethers.

    Science.gov (United States)

    Negin, Saeedeh; Patel, Mohit B; Gokel, Michael R; Meisel, Joseph W; Gokel, George W

    2016-11-17

    Several N,N'-bis(n-alkyl-4,13-diaza[18]crown-6) lariat ethers were found to significantly enhance the potency of rifampicin and tetracycline, but not erythromycin and kanamycin, against the non-pathogenic DH5α and K-12 strains of Escherichia coli when administered at levels below their minimum inhibitory concentrations (MICs). The enhancements in antibiotic potency observed for the lariat ethers ranged from three- to 20-fold, depending on the strain of E. coli, the antibiotic, and the lengths of the alkyl chains attached at the macroring nitrogen atoms. The dialkyl lariat ethers, previously thought to only be cation carriers, formed well-behaved, ion-conducting pores in soybean asolectin membranes, as judged by planar bilayer conductance measurements. The ability of lariat ethers to form stable pores, which appeared to be aggregated, depended in part on alkyl chain length and in part on the composition of the bilayer membrane in which they were studied. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Changes in Cannabis Potency Over the Last 2 Decades (1995-2014): Analysis of Current Data in the United States.

    Science.gov (United States)

    ElSohly, Mahmoud A; Mehmedic, Zlatko; Foster, Susan; Gon, Chandrani; Chandra, Suman; Church, James C

    2016-04-01

    Marijuana is the most widely used illicit drug in the United States and all over the world. Reports indicate that the potency of cannabis preparation has been increasing. This report examines the concentration of cannabinoids in illicit cannabis products seized by the U.S. Drug Enforcement Administration over the last 2 decades, with particular emphasis on Δ(9)-tetrahydrocannabinol and cannabidiol. Samples in this report were received over time from materials confiscated by the Drug Enforcement Administration and processed for analysis using a validated gas chromatography with flame ionization detector method. Between January 1, 1995, and December 31, 2014, 38,681 samples of cannabis preparations were received and analyzed. The data showed that although the number of marijuana samples seized over the last 4 years has declined, the number of sinsemilla samples has increased. Overall, the potency of illicit cannabis plant material has consistently increased over time since 1995 from ~4% in 1995 to ~12% in 2014. The cannabidiol content has decreased on average from ~.28% in 2001 to cannabis plant material from regular marijuana to sinsemilla. This increase in potency poses higher risk of cannabis use, particularly among adolescents. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  4. Determination of pesticides and toxic potency of rainwater samples in western Greece.

    Science.gov (United States)

    Rouvalis, Angela; Karadima, Constantina; Zioris, Ioannis V; Sakkas, Vasilios A; Albanis, Triantafyllos; Iliopoulou-Georgudaki, Joan

    2009-03-01

    Rainwater samples from four municipalities located in Achaia Prefecture, Greece, were collected from March to September 2006. The toxic potency of pollutants present in 36 rainwater samples was tested using Daphnia pulex. The pesticide determination was conducted with GC-MS. Only phosphamidon was detected, which appeared in 52% and 13% of the rural and urban areas, respectively. The toxicity of rainwater was determined in 52% and 46.7% of the rural and urban area samples, respectively. Chemical analyses showed that in rural areas, the PO(4)(3-) ions had higher concentrations than in urban areas. On the other hand, the SO(4)(2-), NO(-)(3), and NO(-)(2) anions are more highly concentrated in urban areas. Correlation analysis proved that the toxicity of the rainwater samples is moderate, affected by the presence of the insecticide only in the rural areas. The results indicated that toxicity can be directly assessed via bioassays, even when unknown pollutants are present.

  5. Potency of veterinary rabies vaccines in The Netherlands: A case for continued vigilance.

    OpenAIRE

    Rooijakkers, E.J.M.; Nieuwenhuijs, J.H.M.; Vermeulen, A.A.; Osterhaus, Albert; Steenis, Bert

    1996-01-01

    textabstractCommercial rabies vaccines, used by veterinarians in the Netherlands, were collected for testing in the mouse potency test. Of the six vaccines tested, two were clearly below the minimal requirements for potency of 1.0 IU. Of these six vaccines the rabies virus glycoprotein (GP) and nucleoprotein (NP) contents were determined in an antigen competition ELISA. The GP content proved to correlate well with the potency found in the mouse potency test (r = 0.95, p < 0.01), whereas no su...

  6. An ex vivo human cartilage repair model to evaluate the potency of a cartilage cell transplant.

    Science.gov (United States)

    Bartz, Christoph; Meixner, Miriam; Giesemann, Petra; Roël, Giulietta; Bulwin, Grit-Carsta; Smink, Jeske J

    2016-11-15

    Cell-based therapies such as autologous chondrocyte implantation are promising therapeutic approaches to treat cartilage defects to prevent further cartilage degeneration. To assure consistent quality of cell-based therapeutics, it is important to be able to predict the biological activity of such products. This requires the development of a potency assay, which assesses a characteristic of the cell transplant before implantation that can predict its cartilage regeneration capacity after implantation. In this study, an ex vivo human cartilage repair model was developed as quality assessment tool for potency and applied to co.don's chondrosphere product, a matrix-associated autologous chondrocyte implant (chondrocyte spheroids) that is in clinical use in Germany. Chondrocyte spheroids were generated from 14 donors, and implanted into a subchondral cartilage defect that was manually generated in human articular cartilage tissue. Implanted spheroids and cartilage tissue were co-cultured ex vivo for 12 weeks to allow regeneration processes to form new tissue within the cartilage defect. Before implantation, spheroid characteristics like glycosaminoglycan production and gene and protein expression of chondrogenic markers were assessed for each donor sample and compared to determine donor-dependent variation. After the co-cultivation, histological analyses showed the formation of repair tissue within the cartilage defect, which varied in amount for the different donors. In the repair tissue, aggrecan protein was expressed and extra-cellular matrix cartilage fibers were present, both indicative for a cartilage hyaline-like character of the repair tissue. The amount of formed repair tissue was used as a read-out for regeneration capacity and was correlated with the spheroid characteristics determined before implantation. A positive correlation was found between high level of aggrecan protein expression in spheroids before implantation and a higher regeneration potential

  7. An ex vivo human cartilage repair model to evaluate the potency of a cartilage cell transplant

    Directory of Open Access Journals (Sweden)

    Christoph Bartz

    2016-11-01

    before implantation and a higher regeneration potential after implantation, reflected by more newly formed repair tissue. Conclusion This demonstrated that aggrecan protein expression levels in spheroids before implantation can potentially be used as surrogate potency assay for the cartilage cell transplant to predict its regenerative capacity after implantation in human patients.

  8. Oral Presentations Have a Significantly Higher Publication Rate, But Not Impact Factors, Than Poster Presentations at the International Society for Study of Lumbar Spine meeting: Review of 1126 Abstracts From 2010 to 2012 Meetings.

    Science.gov (United States)

    Ohtori, Seiji; Orita, Sumihisa; Eguchi, Yawara; Aoki, Yasuchika; Suzuki, Miyako; Kubota, Gou; Inage, Kazuhide; Shiga, Yasuhiro; Abe, Koki; Kinoshita, Hideyuki; Inoue, Masahiro; Kanamoto, Hirohito; Norimoto, Masaki; Umimura, Tomotaka; Furuya, Takeo; Masao, Koda; Maki, Satoshi; Akazawa, Tsutomu; Takahashi, Kazuhisa

    2018-03-05

    A retrospective study. The aim of this study was to determine the publication rate and impact factors (IFs) among all abstracts presented at the 2010 and 2012 meetings of the International Society for the Study of Lumbar Spine (ISSLS). The publication rate of abstracts presented at overseas meetings was reported to be around 50%. However, the publication rate and IFs of oral and poster presentations made at ISSLS meetings were unclear. Moreover, whether the publication rates and IFs differed for papers associated with oral or poster presentations at ISSLS meetings was unknown. We investigated all 1126 abstracts (oral, special posters, general posters) presented at ISSLS meetings held between 2010 and 2012. PubMed was searched to identify publications and IFs were determined using journal citation reports. We also compared the publication rates and IFs between oral and poster presentations. The overall publication rate was 50.1% for three ISSLS meetings (564 publications/1126 abstracts). The overall publication rate for oral presentations, special posters, and general posters given in the 2010 to 2012 meetings was 62.0%, 48.3, and 46.6%, respectively. Overall, papers related to oral presentations had significantly higher publication rates than those of special and general posters (P = 0.0002). The average IFs of publications associated with abstracts presented at three ISSLS meetings was 2.802 for oral presentations, 2.593 for special posters, and 2.589 for general posters. There were no significant differences in average IFs between oral and poster presentations (P > 0.05). The publication rate for abstracts presented at ISSLS meetings was high and similar to publication rates for abstracts presented at other meetings concerning orthopedic and spine research. However, there was no significant difference in IFs between oral and poster presentations, suggesting that abstract evaluations cannot predict IFs of the eventual publication. 4.

  9. Fine-tuning the CAR spacer improves T-cell potency

    Science.gov (United States)

    Watanabe, Norihiro; Bajgain, Pradip; Sukumaran, Sujita; Ansari, Salma; Heslop, Helen E.; Rooney, Cliona M.; Brenner, Malcolm K.; Leen, Ann M.; Vera, Juan F.

    2016-01-01

    ABSTRACT The adoptive transfer of genetically engineered T cells expressing chimeric antigen receptors (CARs) has emerged as a transformative cancer therapy with curative potential, precipitating a wave of preclinical and clinical studies in academic centers and the private sector. Indeed, significant effort has been devoted to improving clinical benefit by incorporating accessory genes/CAR endodomains designed to enhance cellular migration, promote in vivo expansion/persistence or enhance safety by genetic programming to enable the recognition of a tumor signature. However, our efforts centered on exploring whether CAR T-cell potency could be enhanced by modifying pre-existing CAR components. We now demonstrate how molecular refinements to the CAR spacer can impact multiple biological processes including tonic signaling, cell aging, tumor localization, and antigen recognition, culminating in superior in vivo antitumor activity. PMID:28180032

  10. Effect of seed treatment with low-potency laser in peppers plants (Capsicum annuum L.

    Directory of Open Access Journals (Sweden)

    Alexander Álvarez Fonseca,

    2014-01-01

    Full Text Available The influence of seed treatment with low-potency laser radiation on some physiological parameters and yield of peppers plants, California Wonder variety, was studied. The seeds were irradiated with a laser He- Ne, 25 mW powers, at different exposure periods 5, 10, 20, 30 and 60 seconds, using untreated seeds as controls. We evaluated plant height (mm, root length (mm, stem diameter (mm, polar average diameter (mm equatorial mean diameter (mm, mean fruit mass (g and yield per plant (kg.plant-1. The results showed a significant increase (p?0.001 in the indicators of plants height (50 %, root length (13 %, stem diameter (17 %, equatorial mean diameter (7 %, mean fruit mass (13 % and yield per plant (67 %, compared to control.

  11. Discovery and computer aided potency optimization of a novel class of small molecule CXCR4 antagonists.

    Directory of Open Access Journals (Sweden)

    Victoria Vinader

    Full Text Available Amongst the chemokine signalling axes involved in cancer, chemokine CXCL12 acting on chemokine receptor CXCR4 is particularly significant since it orchestrates migration of cancer cells in a tissue-specific metastatic process. High CXCR4 tumour expression is associated with poor prognosis of lung, brain, CNS, blood and breast cancers. We have identified a new class of small molecule CXCR4 antagonists based on the use of computational modelling studies in concert with experimental determination of in vitro activity against CXCL12-induced intracellular calcium mobilisation, proliferation and chemotaxis. Molecular modelling proved to be a useful tool in rationalising our observed potencies, as well as informing the direction of the synthetic efforts aimed at producing more potent compounds.

  12. Sensory irritating potency of some microbial volatile organic compounds (MVOCs) and a mixture of five MVOCs.

    Science.gov (United States)

    Korpi, A; Kasanen, J P; Alarie, Y; Kosma, V M; Pasanen, A L

    1999-01-01

    The authors investigated the ability/potencies of 3 microbial volatile organic compounds and a mixture of 5 microbial volatile organic compounds to cause eye and upper respiratory tract irritation (i.e., sensory irritation), with an animal bioassay. The authors estimated potencies by determining the concentration capable of decreasing the respiratory frequency of mice by 50% (i.e., the RD50 value). The RD50 values for 1-octen-3-ol, 3-octanol, and 3-octanone were 182 mg/m3 (35 ppm), 1359 mg/m3 (256 ppm), and 17586 mg/m3 (3360 ppm), respectively. Recommended indoor air levels calculated from the individual RD50 values for 1-octen-3-ol, 3-octanol, and 3-octanone were 100, 1000, and 13000 microg/m3, respectively-values considerably higher than the reported measured indoor air levels for these compounds. The RD50 value for a mixture of 5 microbial volatile organic compounds was also determined and found to be 3.6 times lower than estimated from the fractional concentrations and the respective RD50s of the individual components. The data support the conclusion that a variety of microbial volatile organic compounds may have some synergistic effects for the sensory irritation response, which constrains the interpretation and application of recommended indoor air levels of individual microbial volatile organic compounds. The results also showed that if a particular component of a mixture was much more potent than the other components, it may dominate the sensory irritation effect. With respect to irritation symptoms reported in moldy houses, the results of this study indicate that the contribution of microbial volatile organic compounds to these symptoms seems less than previously supposed.

  13. The relative potency of inverse opioid agonists and a neutral opioid antagonist in precipitated withdrawal and antagonism of analgesia and toxicity.

    Science.gov (United States)

    Sirohi, Sunil; Dighe, Shveta V; Madia, Priyanka A; Yoburn, Byron C

    2009-08-01

    Opioid antagonists can be classified as inverse agonists and neutral antagonists. In the opioid-dependent state, neutral antagonists are significantly less potent in precipitating withdrawal than inverse agonists. Consequently, neutral opioid antagonists may offer advantages over inverse agonists in the management of opioid overdose. In this study, the relative potency of three opioid antagonists to block opioid analgesia and toxicity and precipitate withdrawal was examined. First, the potency of two opioid inverse agonists (naltrexone and naloxone) and a neutral antagonist (6beta-naltrexol) to antagonize fentanyl-induced analgesia and lethality was determined. The order of potency to block analgesia was naltrexone > naloxone > 6beta-naltrexol (17, 4, 1), which was similar to that to block lethality (13, 2, 1). Next, the antagonists were compared using withdrawal jumping in fentanyl-dependent mice. The order of potency to precipitate withdrawal jumping was naltrexone > naloxone 6beta-naltrexol (1107, 415, 1). The relative potencies to precipitate withdrawal for the inverse agonists compared with the neutral antagonist were dramatically different from that for antagonism of analgesia and lethality. Finally, the effect of 6beta-naltrexol pretreatment on naloxone-precipitated jumping was determined in morphine and fentanyl-dependent mice. 6beta-Naltrexol pretreatment decreased naloxone precipitated withdrawal, indicating that 6beta-naltrexol is a neutral antagonist. These data demonstrate that inverse agonists and neutral antagonists have generally comparable potencies to block opioid analgesia and lethality, whereas the neutral opioid antagonist is substantially less potent in precipitating opioid withdrawal. These results support suggestions that neutral antagonists may have advantages over inverse agonists in the management of opioid overdose.

  14. Insecticidal potency of RNAi-based catalase knockdown in Rhynchophorus ferrugineus (Oliver) (Coleoptera: Curculionidae).

    Science.gov (United States)

    Al-Ayedh, Hassan; Rizwan-Ul-Haq, Muhammad; Hussain, Abid; Aljabr, Ahmed M

    2016-11-01

    Palm trees around the world are prone to notorious Rhynchophorus ferrugineus, which causes heavy losses of palm plantations. In Middle Eastern countries, this pest is a major threat to date palm orchards. Conventional pest control measures with the major share of synthetic insecticides have resulted in insect resistance and environmental issues. Therefore, in order to explore better alternatives, the RNAi approach was employed to knock down the catalase gene in fifth and tenth larval instars with different dsRNA application methods, and their insecticidal potency was studied. dsRNA of 444 bp was prepared to knock down catalase in R. ferrugineus. Out of the three dsRNA application methods, dsRNA injection into larvae was the most effective, followed by dsRNA application by artificial feeding. Both methods resulted in significant catalase knockdown in various tissues, especially the midgut. As a result, the highest growth inhibition of 123.49 and 103.47% and larval mortality of 80 and 40% were observed in fifth-instar larvae, whereas larval growth inhibition remained at 86.83 and 69.08% with larval mortality at 30 and 10% in tenth-instar larvae after dsRNA injection and artificial diet treatment. The topical application method was the least efficient, with the lowest larval growth inhibition of 57.23 and 45.61% and 0% mortality in fifth- and tenth-instar larvae. Generally, better results were noted at the high dsRNA dose of 5 µL. Catalase enzyme is found in most insect body tissues, and thus its dsRNA can cause broad-scale gene knockdown within the insect body, depending upon the application method. Significant larval mortality and growth inhibition after catalase knockdown in R. ferrugineus confirms its insecticidal potency and suggests a bright future for RNAi-based bioinsecticides in pest control. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  15. Potency of veterinary rabies vaccines in The Netherlands: A case for continued vigilance.

    NARCIS (Netherlands)

    E.J.M. Rooijakkers; J.H.M. Nieuwenhuijs; A.A. Vermeulen; A.D.M.E. Osterhaus (Albert); G. van Steenis (Bert)

    1996-01-01

    textabstractCommercial rabies vaccines, used by veterinarians in the Netherlands, were collected for testing in the mouse potency test. Of the six vaccines tested, two were clearly below the minimal requirements for potency of 1.0 IU. Of these six vaccines the rabies virus glycoprotein (GP) and

  16. Vasoconstriction Potency Induced by Aminoamide Local Anesthetics Correlates with Lipid Solubility

    Directory of Open Access Journals (Sweden)

    Hui-Jin Sung

    2012-01-01

    Full Text Available Aminoamide local anesthetics induce vasoconstriction in vivo and in vitro. The goals of this in vitro study were to investigate the potency of local anesthetic-induced vasoconstriction and to identify the physicochemical property (octanol/buffer partition coefficient, pKa, molecular weight, or potency of local anesthetics that determines their potency in inducing isolated rat aortic ring contraction. Cumulative concentration-response curves to local anesthetics (levobupivacaine, ropivacaine, lidocaine, and mepivacaine were obtained from isolated rat aorta. Regression analyses were performed to determine the relationship between the reported physicochemical properties of local anesthetics and the local anesthetic concentration that produced 50% (ED50 of the local anesthetic-induced maximum vasoconstriction. We determined the order of potency (ED50 of vasoconstriction among local anesthetics to be levobupivacaine > ropivacaine > lidocaine > mepivacaine. The relative importance of the independent variables that affect the vasoconstriction potency is octanol/buffer partition coefficient > potency > pKa > molecular weight. The ED50 in endothelium-denuded aorta negatively correlated with the octanol/buffer partition coefficient of local anesthetics (r2=0.9563; P<0.001. The potency of the vasoconstriction in the endothelium-denuded aorta induced by local anesthetics is determined primarily by lipid solubility and, in part, by other physicochemical properties including potency and pKa.

  17. 76 FR 9028 - Guidance for Industry: Potency Tests for Cellular and Gene Therapy Products; Availability

    Science.gov (United States)

    2011-02-16

    ...] Guidance for Industry: Potency Tests for Cellular and Gene Therapy Products; Availability AGENCY: Food and... Therapy Products'' dated January 2011. The guidance document provides manufacturers of cellular and gene... for Industry: Potency Tests for Cellular and Gene Therapy Products'' dated January 2011. The guidance...

  18. Fate and antibacterial potency of anticoccidal drugs and their main abiotic degradation products

    DEFF Research Database (Denmark)

    Hansen, Martin; Krogh, Kristine Andersen; Brandt, Asbjørn

    2009-01-01

    )). The potency of mixtures of two of the compounds, narasin and nicarbazin, was synergistic (more than additive) with 10-fold greater antibacterial potency of the mixture than can be explained by their individual EC(50)-values. The influence of pH, temperature, oxygen concentration and light...

  19. Comparing BMD-derived genotoxic potency estimations across variants of the transgenic rodent gene mutation assay.

    Science.gov (United States)

    Wills, John W; Johnson, George E; Battaion, Hannah L; Slob, Wout; White, Paul A

    2017-12-01

    There is growing interest in quantitative analysis of in vivo genetic toxicity dose-response data, and use of point-of-departure (PoD) metrics such as the benchmark dose (BMD) for human health risk assessment (HHRA). Currently, multiple transgenic rodent (TGR) assay variants, employing different rodent strains and reporter transgenes, are used for the assessment of chemically-induced genotoxic effects in vivo. However, regulatory issues arise when different PoD values (e.g., lower BMD confidence intervals or BMDLs) are obtained for the same compound across different TGR assay variants. This study therefore employed the BMD approach to examine the ability of different TGR variants to yield comparable genotoxic potency estimates. Review of over 2000 dose-response datasets identified suitably-matched dose-response data for three compounds (ethyl methanesulfonate or EMS, N-ethyl-N-nitrosourea or ENU, and dimethylnitrosamine or DMN) across four commonly-used murine TGR variants (Muta™Mouse lacZ, Muta™Mouse cII, gpt delta and BigBlue® lacI). Dose-response analyses provided no conclusive evidence that TGR variant choice significantly influences the derived genotoxic potency estimate. This conclusion was reliant upon taking into account the importance of comparing BMD confidence intervals as opposed to directly comparing PoD values (e.g., comparing BMDLs). Comparisons with earlier works suggested that with respect to potency determination, tissue choice is potentially more important than choice of TGR assay variant. Scoring multiple tissues selected on the basis of supporting toxicokinetic information is therefore recommended. Finally, we used typical within-group variances to estimate preliminary endpoint-specific benchmark response (BMR) values across several TGR variants/tissues. We discuss why such values are required for routine use of genetic toxicity PoDs for HHRA. Environ. Mol. Mutagen. 58:632-643, 2017. © 2017 Her Majesty the Queen in Right of Canada

  20. Building-related symptoms and inflammatory potency of dust from office buildings

    DEFF Research Database (Denmark)

    Allermann, Leila; Pejtersen, Jan; Gunnarsen, Lars Bo

    2007-01-01

    Abstract The aim was to investigate the association between building-related symptoms (BRS) in office buildings and the inflammatory potency of dust (PD). Furthermore, the association between dust potency and various building characteristics was investigated. Occupants of 22 office buildings...... received a retrospective questionnaire about BRS (2301 respondents). Dust was collected from groups of offices and building characteristics were recorded. The potency of a dust sample to induce interleukin-8 (IL-8) secretion from the lung epithelial cell line A549 was measured as the slope of the initial...... linear part of the concentration- response curve. Symptoms of the central nervous system (CNS) were associated with the potency of surface dust (OR ¼ 1.4). This association may be due to an association between an index of CNS symptoms and dust potency in offices of 1-6 occupants (OR ¼ 1.5). No single...

  1. Building-related symptoms and inflammatory potency of dust from office buildings

    DEFF Research Database (Denmark)

    Allermann, L; Pejtersen, J; Gunnarsen, L

    2007-01-01

    UNLABELLED: The aim was to investigate the association between building-related symptoms (BRS) in office buildings and the inflammatory potency of dust (PD). Furthermore, the association between dust potency and various building characteristics was investigated. Occupants of 22 office buildings...... received a retrospective questionnaire about BRS (2301 respondents). Dust was collected from groups of offices and building characteristics were recorded. The potency of a dust sample to induce interleukin-8 (IL-8) secretion from the lung epithelial cell line A549 was measured as the slope of the initial...... linear part of the concentration-response curve. Symptoms of the central nervous system (CNS) were associated with the potency of surface dust (OR = 1.4). This association may be due to an association between an index of CNS symptoms and dust potency in offices of 1-6 occupants (OR = 1.5). No single...

  2. Efficacy of a high potency O1 Manisa monovalent vaccine against heterologous challenge with foot-and-mouth disease virus of O/SEA/Mya-98 lineage in sheep.

    Science.gov (United States)

    Singanallur, N B; Pacheco, J M; Arzt, J; Stenfeldt, C; Fosgate, G T; Rodriguez, L; Vosloo, W

    2017-09-01

    Potency tests for commercial oil-adjuvanted foot-and-mouth disease (FMD) vaccines are usually carried out in cattle, using a full dose (2 ml) of vaccine and homologous virus challenge. However, in sheep the recommended vaccine dose is half of the cattle dose (1 ml) and most vaccines have not been potency tested for this species, especially with heterologous viruses. To determine the efficacy of a high potency (>6PD 50 ) FMD virus (FMDV) O1Manisa vaccine in sheep, we carried out a study using a heterologous FMDV (FMDV O/SKR/2010 - Mya-98 strain) challenge. Groups of seven animals each were vaccinated with 2×, 1×, 1/2× or 1/4× dose (2 ml, 1 ml, 0.5 ml or 0.25 ml respectively) and challenged at 7 days post vaccination (dpv). Only 3 of the 7 sheep in the group vaccinated with 2 ml were protected. With 2 additional groups, receiving double or single doses and challenged at 14 dpv, 4 of 7 sheep were protected in each group. None of the sheep had measurable neutralising antibodies against the vaccine or challenge virus at 7 dpv. However, all vaccinated animals challenged at 14 dpv had a homologous neutralising response against FMDV O1 Manisa on the day of challenge and all but one animal also had a heterologous response to FMDV O/SKR/2010. Infectious FMDV and viral RNA could be found in nasal swabs between 1 and 6 days post challenge (dpc) in most vaccinated sheep, but those vaccinated with higher doses or challenged at 14 dpv showed significant decreases in the level of FMDV detection. Intermittent virus shedding was noticed between 1 and 35 dpc in all vaccinated groups, but persistent infection could be demonstrated only in 4 sheep (20%). This study showed that at the recommended dose, a high potency (>6 PD 50 ) FMDV O1Manisa vaccine does not protect sheep against a heterologous challenge at 7 dpv. However, partial protection was observed when a double dose was used at 7 dpv or when double or single dose vaccinated sheep were challenged at 14 dpv. Copyright

  3. Analysis of cannabis seizures in NSW, Australia: cannabis potency and cannabinoid profile.

    Directory of Open Access Journals (Sweden)

    Wendy Swift

    Full Text Available Recent analysis of the cannabinoid content of cannabis plants suggests a shift towards use of high potency plant material with high levels of Δ(9-tetrahydrocannabinol (THC and low levels of other phytocannabinoids, particularly cannabidiol (CBD. Use of this type of cannabis is thought by some to predispose to greater adverse outcomes on mental health and fewer therapeutic benefits. Australia has one of the highest per capita rates of cannabis use in the world yet there has been no previous systematic analysis of the cannabis being used. In the present study we examined the cannabinoid content of 206 cannabis samples that had been confiscated by police from recreational users holding 15 g of cannabis or less, under the New South Wales "Cannabis Cautioning" scheme. A further 26 "Known Provenance" samples were analysed that had been seized by police from larger indoor or outdoor cultivation sites rather than from street level users. An HPLC method was used to determine the content of 9 cannabinoids: THC, CBD, cannabigerol (CBG, and their plant-based carboxylic acid precursors THC-A, CBD-A and CBG-A, as well as cannabichromene (CBC, cannabinol (CBN and tetrahydrocannabivarin (THC-V. The "Cannabis Cautioning" samples showed high mean THC content (THC+THC-A = 14.88% and low mean CBD content (CBD+CBD-A = 0.14%. A modest level of CBG was detected (CBG+CBG-A = 1.18% and very low levels of CBC, CBN and THC-V (<0.1%. "Known Provenance" samples showed no significant differences in THC content between those seized from indoor versus outdoor cultivation sites. The present analysis echoes trends reported in other countries towards the use of high potency cannabis with very low CBD content. The implications for public health outcomes and harm reduction strategies are discussed.

  4. Bridging the Gap Between Validation and Implementation of Non-Animal Veterinary Vaccine Potency Testing Methods

    Science.gov (United States)

    Dozier, Samantha; Brown, Jeffrey; Currie, Alistair

    2011-01-01

    Simple Summary Many vaccines are tested for quality in experiments that require the use of large numbers of animals in procedures that often cause significant pain and distress. Newer technologies have fostered the development of vaccine quality control tests that reduce or eliminate the use of animals, but the availability of these newer methods has not guaranteed their acceptance by regulators or use by manufacturers. We discuss a strategic approach that has been used to assess and ultimately increase the use of non-animal vaccine quality tests in the U.S. and U.K. Abstract In recent years, technologically advanced high-throughput techniques have been developed that replace, reduce or refine animal use in vaccine quality control tests. Following validation, these tests are slowly being accepted for use by international regulatory authorities. Because regulatory acceptance itself has not guaranteed that approved humane methods are adopted by manufacturers, various organizations have sought to foster the preferential use of validated non-animal methods by interfacing with industry and regulatory authorities. After noticing this gap between regulation and uptake by industry, we began developing a paradigm that seeks to narrow the gap and quicken implementation of new replacement, refinement or reduction guidance. A systematic analysis of our experience in promoting the transparent implementation of validated non-animal vaccine potency assays has led to the refinement of our paradigmatic process, presented here, by which interested parties can assess the local regulatory acceptance of methods that reduce animal use and integrate them into quality control testing protocols, or ensure the elimination of peripheral barriers to their use, particularly for potency and other tests carried out on production batches. PMID:26486625

  5. Deletion Genotypes Reduce Occlusion Body Potency but Increase Occlusion Body Production in a Colombian Spodoptera frugiperda Nucleopolyhedrovirus Population

    Science.gov (United States)

    Barrera, Gloria; Williams, Trevor; Villamizar, Laura; Caballero, Primitivo; Simón, Oihane

    2013-01-01

    A Colombian field isolate (SfCOL-wt) of Spodoptera frugiperda multiple nucleopolyhedrovirus (SfMNPV) is a mixture of different genotypes. To evaluate the insecticidal properties of the different genotypic variants, 83 plaque purified virus were characterized. Ten distinct genotypes were identified (named A through J). SfCOL-A was the most prevalent (71±2%; mean ± SE) showing a PstI restriction profile indistinguishable to that of SfCOL-wt. The remaining nine genotypes presented genomic deletions of 3.8 - 21.8 Kb located mainly between nucleotides 11,436 and 33,883 in the reference genome SfMNPV-B, affecting the region between open reading frames (ORFs) sf20 and sf33. The insecticidal activity of each genotype from SfCOL-wt and several mixtures of genotypes was compared to that of SfCOL-wt. The potency of SfCOL-A occlusion bodies (OBs) was 4.4-fold higher than SfCOL-wt OBs, whereas the speed of kill of SfCOL-A was similar to that of SfCOL-wt. Deletion genotype OBs were similarly or less potent than SfCOL-wt but six deletion genotypes were faster killing than SfCOL-wt. The potency of genotype mixtures co-occluded within OBs were consistently reduced in two-genotype mixtures involving equal proportions of SfCOL-A and one of three deletion genotypes (SfCOL-C, -D or -F). Speed of kill and OB production were improved only when the certain genotype mixtures were co-occluded, although OB production was higher in the SfCOL-wt isolate than in any of the component genotypes, or mixtures thereof. Deleted genotypes reduced OB potency but increased OB production of the SfCOL-wt population, which is structured to maximize the production of OBs in each infected host. PMID:24116220

  6. Deletion genotypes reduce occlusion body potency but increase occlusion body production in a Colombian Spodoptera frugiperda nucleopolyhedrovirus population.

    Directory of Open Access Journals (Sweden)

    Gloria Barrera

    Full Text Available A Colombian field isolate (SfCOL-wt of Spodoptera frugiperda multiple nucleopolyhedrovirus (SfMNPV is a mixture of different genotypes. To evaluate the insecticidal properties of the different genotypic variants, 83 plaque purified virus were characterized. Ten distinct genotypes were identified (named A through J. SfCOL-A was the most prevalent (71±2%; mean ± SE showing a PstI restriction profile indistinguishable to that of SfCOL-wt. The remaining nine genotypes presented genomic deletions of 3.8 - 21.8 Kb located mainly between nucleotides 11,436 and 33,883 in the reference genome SfMNPV-B, affecting the region between open reading frames (ORFs sf20 and sf33. The insecticidal activity of each genotype from SfCOL-wt and several mixtures of genotypes was compared to that of SfCOL-wt. The potency of SfCOL-A occlusion bodies (OBs was 4.4-fold higher than SfCOL-wt OBs, whereas the speed of kill of SfCOL-A was similar to that of SfCOL-wt. Deletion genotype OBs were similarly or less potent than SfCOL-wt but six deletion genotypes were faster killing than SfCOL-wt. The potency of genotype mixtures co-occluded within OBs were consistently reduced in two-genotype mixtures involving equal proportions of SfCOL-A and one of three deletion genotypes (SfCOL-C, -D or -F. Speed of kill and OB production were improved only when the certain genotype mixtures were co-occluded, although OB production was higher in the SfCOL-wt isolate than in any of the component genotypes, or mixtures thereof. Deleted genotypes reduced OB potency but increased OB production of the SfCOL-wt population, which is structured to maximize the production of OBs in each infected host.

  7. Potency Of Bacteriocin For Animal Health And Food Safety

    Directory of Open Access Journals (Sweden)

    Siti Chotiah

    2013-06-01

    Full Text Available The emergence of antibiotic resistance in many bacteria related to animal and public health stresses the importance of decreasing the use of antibiotics in animal production. The reduction of antibiotic application in livestock can only be achieved if alternative antimicrobial strategies are available. A number of strategies have been explored to control microbial pathogens and to improve growth and feed efficiency in livestock without the use of antibiotics. Bacteriocins have been more extensively studied and proposed as potential alternatives to conventional antibiotics in animal husbandry. Bacteriocins are antimicrobial peptides ribosomally synthesized by many species of Bacteria and some strains of Archaea. In general, bacteriocins just exhibited bactericidal or bacteriostatic activity against other bacteria that are closely related to the producing strain. The main mechanisms of bacteriocin activity vary from pore formation in cytoplasmic membranes to the inhibition of cell wall biosynthesis and enzyme activities (RNAse or DNAse in target cells. The use of bacteriocins in probiotic applications, as preservatives, and most excitingly as alternatives to conventional antibiotics is being broadly explored and studied. This review will describe the bacteriocins potency for animal health and food safety, as well as the results of bacteriocin study that had been conducted in Indonesia.

  8. Minor oxygenated cannabinoids from high potency Cannabis sativa L.

    Science.gov (United States)

    Ahmed, Safwat A; Ross, Samir A; Slade, Desmond; Radwan, Mohamed M; Khan, Ikhlas A; ElSohly, Mahmoud A

    2015-09-01

    Nine oxygenated cannabinoids were isolated from a high potency Cannabis sativa L. variety. Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR, HRMS and GC-MS. These minor compounds include four hexahydrocannabinols, four tetrahydrocannabinols, and one hydroxylated cannabinol, namely 9α-hydroxyhexahydrocannabinol, 7-oxo-9α-hydroxyhexa-hydrocannabinol, 10α-hydroxyhexahydrocannabinol, 10aR-hydroxyhexahydrocannabinol, Δ(9)-THC aldehyde A, 8-oxo-Δ(9)-THC, 10aα-hydroxy-10-oxo-Δ(8)-THC, 9α-hydroxy-10-oxo-Δ(6a,10a)-THC, and 1'S-hydroxycannabinol, respectively. The latter compound showed moderate anti-MRSa (IC50 10.0 μg/mL), moderate antileishmanial (IC50 14.0 μg/mL) and mild antimalarial activity against Plasmodium falciparum (D6 clone) and P. falciparum (W2 clone) with IC50 values of 3.4 and 2.3 μg/mL, respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Indanones as high-potency reversible inhibitors of monoamine oxidase.

    Science.gov (United States)

    Mostert, Samantha; Petzer, Anél; Petzer, Jacobus P

    2015-05-01

    Recent reports document that α-tetralone (3,4-dihydro-2H-naphthalen-1-one) is an appropriate scaffold for the design of high-potency monoamine oxidase (MAO) inhibitors. Based on the structural similarity between α-tetralone and 1-indanone, the present study involved synthesis of 34 1-indanone and related indane derivatives as potential inhibitors of recombinant human MAO-A and MAO-B. The results show that C6-substituted indanones are particularly potent and selective MAO-B inhibitors, with IC50 values ranging from 0.001 to 0.030 μM. C5-Substituted indanone and indane derivatives are comparatively weaker MAO-B inhibitors. Although the 1-indanone and indane derivatives are selective inhibitors of the MAO-B isoform, a number of homologues are also potent MAO-A inhibitors, with three homologues possessing IC50 values 1-indanone as a reversible MAO inhibitor with a competitive mode of inhibition. It may be concluded that 1-indanones are promising leads for the design of therapies for neurodegenerative and neuropsychiatric disorders such as Parkinson's disease and depression. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Slow self-activation enhances the potency of viridin prodrugs.

    Science.gov (United States)

    Blois, Joseph; Yuan, Hushan; Smith, Adam; Pacold, Michael E; Weissleder, Ralph; Cantley, Lewis C; Josephson, Lee

    2008-08-14

    When the viridin wortmannin (Wm) is modified by reaction with certain nucleophiles at the C20 position, the compounds obtained exhibit an improved antiproliferative activity even though a covalent reaction between C20 and a lysine in the active site of PI3 kinase is essential to Wm's ability to inhibit this enzyme. Here we show that this improved potency results from an intramolecular attack by the C6 hydroxyl group that slowly converts these inactive prodrugs to the active species Wm over the 48 h duration of the antiproliferative assay. Our results provide a guide for selecting Wm-like compounds to maximize kinase inhibition with the variety of protocols used to assess the role of PI3 kinase in biological systems, or for achieving optimal therapeutic effects in vivo . In addition, the slow self-activation of WmC20 derivatives provides a mechanism that can be exploited to obtain kinase inhibitors endowed with physical and pharmacokinetic properties far different from man-made kinase inhibitors because they do not bind to kinase active sites.

  11. Potency of Thorium and Uranium in West Bangka Region

    International Nuclear Information System (INIS)

    Ngadenin; Heri Syaeful; Kurnia Setiawan Widana; Muhammad Nurdin

    2014-01-01

    Thorium and uranium in Bangka Island are mainly found in monazite mineral. In the geological point of view the monazite formed in S type granite, sandstones and alluvial deposits. In Bangka Barat where several S types granite and also alluvial deposits and this area considered as a potential area for monazite placer. S type granites are predicted as a source of monazite while alluvial deposits are considered as a dispersion place for deposition of monazite. The purpose of this study is to determine the geological information and to know the hypothetical potency of thorium and uranium resources in alluvial deposits. The methods used in this study are geological mapping, measurement of thorium and uranium contents in the rock, sampling of granite for petrographic analysis, sampling of heavy mineral in alluvial deposits for grain size analysis. Results of the research show that the lithology of West Bangka region composed of schist unit, meta-sandstone unit, granite intrusion, diabase intrusion, sandstone unit and alluvial deposits. Monazite is found in granite intrusion, sandstone unit and alluvial deposits. Evolving fault strand to northwest-southeast, northeast-southwest and west-east. The results of the grain size analysis of heavy mineral shows the average percentage of monazite in the heavy mineral is 6.34%. Other potential minerals contained in placer deposits are zircon 36.65%, ilmenite 19.67% and cassiterite 14.75%. (author)

  12. Temporal Variation in the Estrogenicity of a Sewage Treatment Plant Effluent and its Biological Significance

    Science.gov (United States)

    This paper describes variations in the estrogenic potency of effluent from a "model" wastewater treatment plant in Duluth, MN, and explores the significance of these variations relative to sampling approaches for monitoring effluents and their toxicity to fish.

  13. Using a mass balance to determine the potency loss during the production of a pharmaceutical blend.

    Science.gov (United States)

    Mackaplow, Michael B

    2010-09-01

    The manufacture of a blend containing the active pharmaceutical ingredient (API) and inert excipients is a precursor for the production of most pharmaceutical capsules and tablets. However, if there is a net water gain or preferential loss of API during production, the potency of the final drug product may be less than the target value. We use a mass balance to predict the mean potency loss during the production of a blend via wet granulation and fluidized bed drying. The result is an explicit analytical equation for the change in blend potency a function of net water gain, solids losses (both regular and high-potency), and the fraction of excipients added extragranularly. This model predicts that each 1% gain in moisture content (as determined by a loss on drying test) will decrease the API concentration of the final blend at least 1% LC. The effect of pre-blend solid losses increases with their degree of superpotency. This work supports Quality by Design by providing a rational method to set the process design space to minimize blend potency losses. When an overage is necessary, the model can help justify it by providing a quantitative, first-principles understanding of the sources of potency loss. The analysis is applicable to other manufacturing processes where the primary sources of potency loss are net water gain and/or mass losses.

  14. Examining the profile of high-potency cannabis and its association with severity of cannabis dependence.

    Science.gov (United States)

    Freeman, T P; Winstock, A R

    2015-11-01

    Cannabis use is decreasing in England and Wales, while demand for cannabis treatment in addiction services continues to rise. This could be partly due to an increased availability of high-potency cannabis. Adults residing in the UK were questioned about their drug use, including three types of cannabis (high potency: skunk; low potency: other grass, resin). Cannabis types were profiled and examined for possible associations between frequency of use and (i) cannabis dependence, (ii) cannabis-related concerns. Frequent use of high-potency cannabis predicted a greater severity of dependence [days of skunk use per month: b = 0.254, 95% confidence interval (CI) 0.161-0.357, p effect became stronger as age decreased (b = -0.006, 95% CI -0.010 to -0.002, p = 0.004). By contrast, use of low-potency cannabis was not associated with dependence (days of other grass use per month: b = 0.020, 95% CI -0.029 to 0.070, p = 0.436; days of resin use per month: b = 0.025, 95% CI -0.019 to 0.067, p = 0.245). Frequency of cannabis use (all types) did not predict severity of cannabis-related concerns. High-potency cannabis was clearly distinct from low-potency varieties by its marked effects on memory and paranoia. It also produced the best high, was preferred, and most available. High-potency cannabis use is associated with an increased severity of dependence, especially in young people. Its profile is strongly defined by negative effects (memory, paranoia), but also positive characteristics (best high, preferred type), which may be important when considering clinical or public health interventions focusing on cannabis potency.

  15. Introduction of a methoxymethyl side chain into p-phenylenediamine attenuates its sensitizing potency and reduces the risk of allergy induction

    Energy Technology Data Exchange (ETDEWEB)

    Goebel, Carsten, E-mail: goebel.c.1@pg.com [The Procter and Gamble Co., Central Product Safety and Communications, Darmstadt (Germany); Troutman, John [The Procter and Gamble Co., Central Product Safety, Cincinnati, OH (United States); Hennen, Jenny [Dept. of Environmental Toxicology, Trier University, Trier (Germany); Rothe, Helga; Schlatter, Harald [The Procter and Gamble Co., Central Product Safety and Communications, Darmstadt (Germany); Gerberick, G. Frank [The Procter and Gamble Co., Central Product Safety, Cincinnati, OH (United States); Blömeke, Brunhilde [Dept. of Environmental Toxicology, Trier University, Trier (Germany)

    2014-02-01

    The strong sensitizing potencies of the most important primary intermediates of oxidative hair dyes, p-phenylenediamine (PPD) and p-toluylenediamine (PTD, i.e. 2-methyl-PPD) are well established. They are considered as the key sensitizers in hair dye allergic contact dermatitis. While modification of their molecular structure is expected to alter their sensitizing properties, it may also impair their color performance. With introduction of a methoxymethyl side chain we found the primary intermediate 2-methoxymethyl-p-phenylenediamine (ME-PPD) with excellent hair coloring performance but significantly reduced sensitizing properties compared to PPD and PTD: In vitro, ME-PPD showed an attenuated innate immune response when analyzed for its protein reactivity and dendritic cell activation potential. In vivo, the effective concentration of ME-PPD necessary to induce an immune response 3-fold above vehicle control (EC3 value) in the local lymph node assay (LLNA) was 4.3%, indicating a moderate skin sensitizing potency compared to values of 0.1 and 0.17% for PPD and PTD, respectively. Finally, assessing the skin sensitizing potency of ME-PPD under consumer hair dye usage conditions through a quantitative risk assessment (QRA) indicated an allergy induction risk negligible compared to PPD or PTD. - Highlights: • Methoxymethyl side chain in p-phenylenediamine reduces its strong skin sensitizing properties. • Reduced protein reactivity and dendritic cell activation. • Reduced skin sensitizing potency in local lymph node assay (LLNA). • Negligible allergy induction risk under hair dye usage conditions.

  16. Introduction of a methoxymethyl side chain into p-phenylenediamine attenuates its sensitizing potency and reduces the risk of allergy induction

    International Nuclear Information System (INIS)

    Goebel, Carsten; Troutman, John; Hennen, Jenny; Rothe, Helga; Schlatter, Harald; Gerberick, G. Frank; Blömeke, Brunhilde

    2014-01-01

    The strong sensitizing potencies of the most important primary intermediates of oxidative hair dyes, p-phenylenediamine (PPD) and p-toluylenediamine (PTD, i.e. 2-methyl-PPD) are well established. They are considered as the key sensitizers in hair dye allergic contact dermatitis. While modification of their molecular structure is expected to alter their sensitizing properties, it may also impair their color performance. With introduction of a methoxymethyl side chain we found the primary intermediate 2-methoxymethyl-p-phenylenediamine (ME-PPD) with excellent hair coloring performance but significantly reduced sensitizing properties compared to PPD and PTD: In vitro, ME-PPD showed an attenuated innate immune response when analyzed for its protein reactivity and dendritic cell activation potential. In vivo, the effective concentration of ME-PPD necessary to induce an immune response 3-fold above vehicle control (EC3 value) in the local lymph node assay (LLNA) was 4.3%, indicating a moderate skin sensitizing potency compared to values of 0.1 and 0.17% for PPD and PTD, respectively. Finally, assessing the skin sensitizing potency of ME-PPD under consumer hair dye usage conditions through a quantitative risk assessment (QRA) indicated an allergy induction risk negligible compared to PPD or PTD. - Highlights: • Methoxymethyl side chain in p-phenylenediamine reduces its strong skin sensitizing properties. • Reduced protein reactivity and dendritic cell activation. • Reduced skin sensitizing potency in local lymph node assay (LLNA). • Negligible allergy induction risk under hair dye usage conditions

  17. Anti-inflammatory potency testing of topical corticosteroids and calcineurin inhibitors in human volunteers sensitized to diphenylcyclopropenone

    DEFF Research Database (Denmark)

    Mose, Kristian F; Andersen, Flemming; Røpke, Mads A

    2018-01-01

    by visual scoring and measurements of the oedema thickness with ultrasound. RESULTS: When applied both before and after the DPCP challenge, significant anti-inflammatory effects were seen in descending order for tacrolimus 0.1% ointment, clobetasol propionate ointment, betamethasone valerate ointment...... in which the inflammation of experimentally-induced allergic patch test reactions is quantified by objective measurement allows an analysis of the anti-inflammatory potency of not only topical corticosteroids, but also of drugs that have no effect on vasoconstriction. The method allowed comparison...

  18. Noise frame duration, masking potency and whiteness of temporal noise.

    Science.gov (United States)

    Kukkonen, Heljä; Rovamo, Jyrki; Donner, Kristian; Tammikallio, Marja; Raninen, Antti

    2002-09-01

    Because of the limited contrast range, increasing the duration of the noise frame is often the only option for increasing the masking potency of external, white temporal noise. This, however, reduces the high-frequency cutoff beyond which noise is no longer white. This study was conducted to determine the longest noise frame duration that produces the strongest masking effect and still mimics white noise on the detection of sinusoidal flicker. Contrast energy thresholds (E(th)) were measured for flicker at 1.25 to 20 Hz in strong, purely temporal (spatially uniform), additive, external noise. The masking power of white external noise, characterized by its spectral density at zero frequency N0, increases with the duration of the noise frame. For short noise frame durations, E(th) increased in direct proportion to N0, keeping the nominal signal-to-noise ratio [SNR = (E(th)/N0)(0.5)] constant at threshold. The masking effect thus increased with the duration of the noise frame and the noise mimicked white noise. When noise frame duration and N0 increased further, the nominal SNR at threshold started to decrease, indicating that noise no longer mimicked white noise. The minimum number of noise frames per flicker cycle needed to mimic white noise decreased with increasing flicker frequency from 8.3 at 1.25 Hz to 1.6 at 20 Hz. The critical high-frequency cutoff of detection-limiting temporal noise in terms of noise frames per signal cycle depends on the temporal frequency of the signal. This is opposite to the situation in the spatial domain and must be taken into consideration when temporal signals are masked with temporal noise.

  19. POTENCY OF KIPO, A TRADITIONAL FOOD FROM KOTAGEDE – YOGYAKARTA

    Directory of Open Access Journals (Sweden)

    Wahyu Supartono

    2016-04-01

    Full Text Available Kipo is a traditional food from Kotagede Region – Yogyakarta, which is produced from glutinous rice. It was processed through some steps such as weighing, mixing, melting, roasting and packing. This traditional food is not popular like other traditional foods such as gudeg or yangko. Problems concerning this situation were, the information of kipo was not well delivered to the consumers and people who were doing business with kipo were very limited and only in Kotagede.This research was aimed to disclosure the potency of kipo, if it was developed as industrial foods. The aspects of market, technical and financial were conducted and analyzed. These aspects were used for giving considerations, if this product could be developed in the future. The results depicted, that from the market aspect, value kipoconsumer’s attitude index was good (3.8845 from 5. The technical aspect showed, that this industry was quite small scale with processing capacity only 19 kg product per day, used 5 menpower and 60 m2 area.Based on the financial aspect at actual capacity, the results showed Net Present Value was Rp. 70,180,679; Payback Period 1.21 years; Profitability Index 5.51;Internal Rate of Return 98.5% and Break Even Point was Rp. 505,414 or 212,693 kipo. This industry was very sensitive to the increase of interest level, total cost and decrease of price product. Some challenged aspects of kipo were, it was produced from naural sources such as glutinous rice, coconut, brown sugar and also natural food colouring agent. The traditional process was still kept and the people could enjoy how it was produced. This is the challenge to develop the traditional food as part of culinary or historical tour.

  20. Indian women with higher serum concentrations of folate and vitamin B12 are significantly less likely to be infected with carcinogenic or high-risk (HR types of human papillomaviruses (HPVs

    Directory of Open Access Journals (Sweden)

    Chandrika J Piyathilake

    2010-01-01

    Full Text Available Chandrika J Piyathilake1, Suguna Badiga1, Proma Paul2, Vijayaraghavan K3, Haripriya Vedantham3, Mrudula Sudula3, Pavani Sowjanya3, Gayatri Ramakrishna4, Keerti V Shah5, Edward E Partridge6, Patti E Gravitt21Department of Nutrition Sciences, The University of Alabama at Birmingham (UAB, Birmingham, AL, USA; 2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; 3SHARE INDIA, Mediciti Institute of Medical Sciences, Ghanpur, India; 4Center for DNA Fingerprinting and Diagnostics, Hyderabad, India; 5Department of Molecular biology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD USA; 6UAB Comprehensive Cancer Center, The University of Alabama Birmingham (UAB, Birmingham, AL, USABackground: Studies conducted in the USA have demonstrated that micronutrients such as folate and vitamin B12 play a significant role in modifying the natural history of high-risk human papillomaviruses (HR-HPVs, the causative agent for developing invasive cervical cancer (CC and its precursor lesions.Objective: The purpose of the current study was to investigate whether these micronutrients have similar effects on HR-HPV infections in Indian women.Methods: The associations between serum concentrations of folate and vitamin B12 and HR-HPV infections were evaluated in 724 women who participated in a CC screening study in the southern state of Andhra Pradesh, India. Serum folate and vitamin B12 concentrations were measured by using a competitive radio-binding assay. Digene hybrid capture 2 (HC2 assay results were used to categorize women into two groups, positive or negative for HR-HPVs. Unconditional logistic regression models specified a binary indicator of HC2 (positive/negative as the dependent variable and serum folate concentrations combined with serum vitamin B12 concentrations as the independent predictor of primary interest. Models were fitted, adjusting for age, education, marital status, parity

  1. The incidence of kidney injury for patients treated with a high-potency versus moderate-potency statin regimen after an acute coronary syndrome.

    Science.gov (United States)

    Sarma, Amy; Cannon, Christopher P; de Lemos, James; Rouleau, Jean L; Lewis, Eldrin F; Guo, Jianping; Mega, Jessica L; Sabatine, Marc S; O'Donoghue, Michelle L

    2014-05-01

    Observational studies have raised concerns that high-potency statins increase the risk of acute kidney injury. We therefore examined the incidence of kidney injury across 2 randomized trials of statin therapy. PROVE IT-TIMI 22 enrolled 4162 subjects after an acute coronary syndrome (ACS) and randomized them to atorvastatin 80 mg/day versus pravastatin 40 mg/day. A-to-Z enrolled 4497 subjects after ACS and randomized them to a high-potency (simvastatin 40 mg/day × 1 months, then simvastatin 80 mg/day) versus a delayed moderate-potency statin strategy (placebo × 4 months, then simvastatin 20 mg/day). Serum creatinine was assessed centrally at serial time points. Adverse events (AEs) relating to kidney injury were identified through database review. Across both trials, mean serum creatinine was similar between treatment arms at baseline and throughout follow-up. In A-to-Z, the incidence of a 1.5-fold or ≥ 0.3 mg/dL rise in serum creatinine was 11.4% for subjects randomized to a high-potency statin regimen versus 12.4% for those on a delayed moderate-potency regimen (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.76 to 1.10; P=0.33). In PROVE IT-TIMI 22, the incidence was 9.4% for subjects randomized to atorvastatin 80 mg/day and 10.6% for subjects randomized to pravastatin 40 mg/day (OR, 0.88; 95% CI, 0.71 to 1.09; P=0.25). Consistent results were observed for different kidney injury thresholds and in individuals with diabetes mellitus or with moderate renal dysfunction. The incidence of kidney injury-related adverse events (AEs) was not statistically different for patients on a high-potency versus moderate-potency statin regimen (OR, 1.06; 95% CI, 0.68 to 1.67; P=0.78). For patients enrolled in 2 large randomized trials of statin therapy after ACS, the use of a high-potency statin regimen did not increase the risk of kidney injury.

  2. Early biochemical recurrence, urinary continence and potency outcomes following robot-assisted radical prostatectomy

    DEFF Research Database (Denmark)

    Berg, Kasper Drimer; Thomsen, Frederik Birkebæk; Hvarness, Helle

    2014-01-01

    OBJECTIVE: The aim of this study was to describe recovery of urinary continence and potency and report oncological and functional outcomes using the survival, continence and potency (SCP) system for patients undergoing robot-assisted radical prostatectomy (RARP). MATERIAL AND METHODS: From 2009...... with preoperative ESI, 77.6% (67.9-86.1) and 34.4% (24.1-47.5) maintained ESI 12 months postoperatively after bilateral and unilateral nerve-sparing surgery (NS), respectively. NS (p .... Using the SCP system and defining potency as ESI, functional and oncological success 12 months after surgery was achieved in 69 out of 135 (51.1%) preoperative continent and potent patients who underwent unilateral or bilateral NS, and did not require adjuvant treatment; when defining potency as IIEF...

  3. Specific Stereoisomeric Conformations Determine the Drug Potency of Cladosporin Scaffold against Malarial Parasite.

    Science.gov (United States)

    Das, Pronay; Babbar, Palak; Malhotra, Nipun; Sharma, Manmohan; Jachak, Gorakhnath R; Gonnade, Rajesh G; Shanmugam, Dhanasekaran; Harlos, Karl; Yogavel, Manickam; Sharma, Amit; Reddy, D Srinivasa

    2018-05-21

    The dependence of drug potency on diastereomeric configurations is a key facet. Using a novel general divergent synthetic route for a three-chiral centre anti-malarial natural product cladosporin, we built its complete library of stereoisomers (cladologs) and assessed their inhibitory potential using parasite-, enzyme- and structure-based assays. We show that potency is manifest via tetrahyropyran ring conformations that are housed in the ribose binding pocket of parasite lysyl tRNA synthetase (KRS). Strikingly, drug potency between top and worst enantiomers varied 500-fold, and structures of KRS-cladolog complexes reveal that alterations at C3 and C10 are detrimental to drug potency where changes at C3 are sensed by rotameric flipping of Glutamate332. Given that scores of anti-malarial and anti-infective drugs contain chiral centers, this work provides a new foundation for focusing on inhibitor stereochemistry as a facet of anti-microbial drug development.

  4. High Efficacy but Low Potency of δ-Opioid Receptor-G Protein Coupling in Brij-58-Treated, Low-Density Plasma Membrane Fragments.

    Science.gov (United States)

    Roubalova, Lenka; Vosahlikova, Miroslava; Brejchova, Jana; Sykora, Jan; Rudajev, Vladimir; Svoboda, Petr

    2015-01-01

    HEK293 cells stably expressing PTX-insensitive δ-opioid receptor-Gi1α (C351I) fusion protein were homogenized, treated with low concentrations of non-ionic detergent Brij-58 at 0°C and fractionated by flotation in sucrose density gradient. In optimum range of detergent concentrations (0.025-0.05% w/v), Brij-58-treated, low-density membranes exhibited 2-3-fold higher efficacy of DADLE-stimulated, high-affinity [32P]GTPase and [35S]GTPγS binding than membranes of the same density prepared in the absence of detergent. The potency of agonist DADLE response was significantly decreased. At high detergent concentrations (>0.1%), the functional coupling between δ-opioid receptors and G proteins was completely diminished. The same detergent effects were measured in plasma membranes isolated from PTX-treated cells. Therefore, the effect of Brij-58 on δ-opioid receptor-G protein coupling was not restricted to the covalently bound Gi1α within δ-opioid receptor-Gi1α fusion protein, but it was also valid for PTX-sensitive G proteins of Gi/Go family endogenously expressed in HEK293 cells. Characterization of the direct effect of Brij-58 on the hydrophobic interior of isolated plasma membranes by steady-state anisotropy of diphenylhexatriene (DPH) fluorescence indicated a marked increase of membrane fluidity. The time-resolved analysis of decay of DPH fluorescence by the "wobble in cone" model of DPH motion in the membrane indicated that the exposure to the increasing concentrations of Brij-58 led to a decreased order and higher motional freedom of the dye. Limited perturbation of plasma membrane integrity by low concentrations of non-ionic detergent Brij-58 results in alteration of δ-OR-G protein coupling. Maximum G protein-response to agonist stimulation (efficacy) is increased; affinity of response (potency) is decreased. The total degradation plasma membrane structure at high detergent concentrations results in diminution of functional coupling between

  5. Assessment of the skin sensitising potency of the lower alkyl methacrylate esters.

    Science.gov (United States)

    Kimber, Ian; Pemberton, Mark A

    2014-10-01

    There is continued interest in, and imperatives for, the classification of contact allergens according to their relative skin sensitising potency. However, achieving that end can prove problematic, not least when there is an apparent lack of concordance between experimental assessments of potency and the prevalence allergic contact dermatitis as judged by clinical experience. For the purpose of exploring this issue, and illustrating the important considerations that are required to reach sound judgements about potency categorisation, the lower alkyl methacrylate esters (LAM) have been employed here as a case study. Although the sensitising potential of methyl methacrylate (MMA) has been reviewed previously, there is available new information that is relevant for assessment of skin sensitising potency. Moreover, for the purposes of this article, analyses have been extended to include also other LAM for which relevant data are available: ethyl methacrylate (EMA), n-butyl methacrylate (nBMA), isobutyl methacrylate (iBMA), and 2-ethylhexyl methacrylate (EHMA). In addressing the skin sensitising activity of these chemicals and in drawing conclusions regarding relative potency, a number of sources of information has been considered, including estimates of potency derived from local lymph node assay (LLNA) data, the results of guinea pig assays, and data derived from in silico methods and from recently developed in vitro approaches. Moreover, clinical experience of skin sensitisation of humans by LAM has also been evaluated. The conclusion drawn is that MMA and other LAM are contact allergens, but that none of these chemicals has any more than weak skin sensitising potency. We have also explored here the possible bases for this modest sensitising activity. Finally, the nature of exposure to LAM has been reviewed briefly and on the basis of that information, together with an understanding of skin sensitising potency, a risk assessment has been prepared. Copyright © 2014

  6. Assessment of pepper spray product potency in Asian and Caucasian forearm skin using transepidermal water loss, skin temperature and reflectance colorimetry.

    Science.gov (United States)

    Pershing, Lynn K; Reilly, Christopher A; Corlett, Judy L; Crouch, Dennis J

    2006-01-01

    Historically, pepper spray product potency has been established using a taste test evaluation. A taste test is subjective and may not be appropriate for assessing pepper potency in skin. The current study evaluated chemically diverse pepper sprays in human forearm skin using three objective, noninvasive parameters: transepidermal water loss, skin surface temperature and erythema, as a means for assessing dermal pharmacology, toxicology and product potency. Five commercial pepper spray products containing various capsaicinoid analogs at various concentrations were evaluated in duplicate on volar forearms of six Caucasians and six Asians using a 10 min exposure. Mean surface skin temperature, transepidermal water loss results were highly variable and therefore did not demonstrate dose responsive behavior to increasing capsaicinoid concentrations. Erythema, as measured by increases in a* (reflected light in the red-to-green color spectrum) of the L*a*b* uniform color scale, was superior among parameters evaluated in discriminating pepper spray potency and correlated well with the relative and total capsaicinoid concentration in the products. Products containing greater than 16 mg ml(-1) capsaicinoid concentration produced greater erythema responses in Caucasians than Asians. Asians responded greater to the synthetic analog, nonivamide, than to mixtures of capsaicinoids, while Caucasians responded equally to both capsaicinoid analogs. Thus, pepper spray product potency in human skin reflects the total capsaicinoid concentration, the specific capsaicin analog(s) present, and the race of the individual exposed. The finding that the reflectance colorimeter a* scale can differentiate these parameters in skin will have a significant impact on evaluating the use and efficacy of pepper spray products in humans. 2005 John Wiley & Sons, Ltd.

  7. What is the true in vitro potency of oxytetracycline for the pig pneumonia pathogens Actinobacillus pleuropneumoniae and Pasteurella multocida?

    Science.gov (United States)

    Dorey, L; Hobson, S; Lees, P

    2017-10-01

    The pharmacodynamics of oxytetracycline was determined for pig respiratory tract pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida. Indices of potency were determined for the following: (i) two matrices, broth and pig serum; (ii) five overlapping sets of twofold dilutions; and (iii) a high strength starting culture. For A. pleuropneumoniae, minimum inhibitory concentration (MIC) was similar for the two matrices, but for P. multocida, differences were marked and significantly different. MIC and minimum bactericidal concentration (MBC) serum: broth ratios for A. pleuropneumoniae were 0.83:1 and 1.22:1, respectively, and corresponding values for P. multocida were 22.0:1 and 7.34:1. For mutant prevention concentration (MPC) serum: broth ratios were 0.79:1 (A. pleuropneumoniae) and 20.9:1 (P. multocida). These ratios were corrected for serum protein binding to yield fraction unbound (fu) serum: broth MIC ratios of 0.24:1 (A. pleuropneumoniae) and 6.30:1 (P. multocida). Corresponding fu serum: broth ratios for MPC were almost identical, 0.23:1 and 6.08:1. These corrections for protein binding did not account for potency differences between serum and broth for either species; based on fu serum MICs, potency in serum was approximately fourfold greater than predicted for A. pleuropneumoniae and sixfold smaller than predicted for P. multocida. For both broth and serum and both bacterial species, MICs were also dependent on initial inoculum strength. The killing action of oxytetracycline had the characteristics of codependency for both A. pleuropneumoniae and P. multocida in both growth media. The in vitro potency of oxytetracycline in pig serum is likely to be closer to the in vivo plasma/serum concentration required for efficacy than potency estimated in broths. © 2017 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

  8. Fasxiator, a novel factor XIa inhibitor from snake venom, and its site-specific mutagenesis to improve potency and selectivity.

    Science.gov (United States)

    Chen, W; Carvalho, L P D; Chan, M Y; Kini, R M; Kang, T S

    2015-02-01

    Bleeding remains a major limitation of standard anticoagulant drugs that target the extrinsic and common coagulation pathways. Recently, intrinsic coagulation factors are increasingly being investigated as alternative targets for developing anticoagulant drugs with lower bleeding risk. Goals were to (i) identify novel anticoagulants selectively targeting intrinsic coagulation pathway and (ii) characterize and further improve the properties of the identified anticoagulants. We have isolated and sequenced a specific factor XIa (FXIa) inhibitor, henceforth named Fasxiator, from the venom of the banded krait snake, Bungarus fasciatus. It is a Kunitz-type protease inhibitor that prolonged activated partial thromboplastin time without significant effects on prothrombin time. Fasxiator was recombinantly expressed (rFasxiator), purified, and characterized to be a slow-type inhibitor of FXIa that exerts its anticoagulant activities (doubled activated partial thromboplastin time at ~ 3 μmol L(-1) ) by selectively inhibiting human FXIa in in vitro assays. A series of mutants were subsequently generated to improve the potency and selectivity of recombinant rFasxiator. rFasxiatorN17R,L19E showed the best balance between potency (IC50 ~ 1 nmol L(-1) ) and selectivity (> 100 times). rFasxiatorN17R,L19E is a competitive slow-type inhibitor of FXIa (Ki  = 0.86 nmol L(-1) ), possesses anticoagulant activity that is ~ 10 times stronger in human plasma than in murine plasma, and prolonged the occlusion time of mice carotid artery in FeCl3 -induced thrombosis models. We have isolated an exogenous FXIa specific inhibitor, engineered it to improve its potency by ~ 1000 times and demonstrated its in vitro and in vivo efficacy. These proof-of-principle data supported the further development of Fasxiator as a novel anticoagulant candidate. © 2014 International Society on Thrombosis and Haemostasis.

  9. Retained Myogenic Potency of Human Satellite Cells from Torn Rotator Cuff Muscles Despite Fatty Infiltration.

    Science.gov (United States)

    Koide, Masashi; Hagiwara, Yoshihiro; Tsuchiya, Masahiro; Kanzaki, Makoto; Hatakeyama, Hiroyasu; Tanaka, Yukinori; Minowa, Takashi; Takemura, Taro; Ando, Akira; Sekiguchi, Takuya; Yabe, Yutaka; Itoi, Eiji

    2018-01-01

    Rotator cuff tears (RCTs) are a common shoulder problem in the elderly that can lead to both muscle atrophy and fatty infiltration due to less physical load. Satellite cells, quiescent cells under the basal lamina of skeletal muscle fibers, play a major role in muscle regeneration. However, the myogenic potency of human satellite cells in muscles with fatty infiltration is unclear due to the difficulty in isolating from small samples, and the mechanism of the progression of fatty infiltration has not been elucidated. The purpose of this study was to analyze the population of myogenic and adipogenic cells in disused supraspinatus (SSP) and intact subscapularis (SSC) muscles of the RCTs from the same patients using fluorescence-activated cell sorting. The microstructure of the muscle with fatty infiltration was observed as a whole mount condition under multi-photon microscopy. Myogenic differentiation potential and gene expression were evaluated in satellite cells. The results showed that the SSP muscle with greater fatty infiltration surrounded by collagen fibers compared with the SSC muscle under multi-photon microscopy. A positive correlation was observed between the ratio of muscle volume to fat volume and the ratio of myogenic precursor to adipogenic precursor. Although no difference was observed in the myogenic potential between the two groups in cell culture, satellite cells in the disused SSP muscle showed higher intrinsic myogenic gene expression than those in the intact SSC muscle. Our results indicate that satellite cells from the disused SSP retain sufficient potential of muscle growth despite the fatty infiltration.

  10. Which mode and potency of electrocoagulation yields the Smallest Unobstructed Area of the Fallopian Tubes?

    Science.gov (United States)

    Campagnolo, Marcelo Ivo; Reis, Ricardo Dos; Santos, Marcele Oliveira Dos; Kliemann, Lúcia Maria; Savaris, Ricardo Francalacci

    2018-05-29

     To determine which mode and potency of electrocoagulation, using a modern electrosurgical generator, yields the smallest unobstructed area of the Fallopian tubes.  In an experimental study, tubes from 48 hysterectomies or tubal ligation were evaluated. Tubes were randomly allocated to one of the following groups: group A) 25 W x 5 seconds ( n  = 17); group B) 30 W x 5 seconds ( n  = 17); group C) 35 W x 5 seconds ( n  = 18), group D) 40 W x 5 seconds ( n  = 20); group E) 40 W x 5 seconds with visual inspection (blanch, swells, collapse) ( n  = 16); group F) 50 W x 5 seconds ( n  = 8). Bipolar electrocoagulation was performed in groups A to E, and monopolar electrocoagulation was performed in group F. Coagulation mode was used in all groups. Digital photomicrography of the transversal histological sections of the isthmic segment of the Fallopian tube were taken, and the median percentage of unobstructed luminal area (mm 2 ) was measured with ImageJ software (ImageJ, National Institutes of Health, Bethesda, MD, USA). The Kruskal-Wallis test or analysis of variance (ANOVA) was used for statistical analysis.  Ninety-six Fallopian tube sections were analyzed. The smallest median occluded area (%; range) of the Fallopian tube was obtained in the group with 40 W with visual inspection (8.3%; 0.9-40%), followed by the groups 25 W (9.1%; 0-35.9%), 40 W (14.2; 0.9-43.2%), 30 W (14.2; 0.9-49.7%), 35 W (15.1; 3-46.4%) and 50 W (38.2; 3.1-51%). No statistically significant difference was found among groups ( p  = 0.09, Kruskal-Wallis test).  The smallest unobstructed area was obtained with power setting at 40 W with visual inspection using a modern electrosurgical generator. However, no statistically significant difference in the unobstructed area was observed among the groups using these different modes and potencies. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

  11. Prenatal developmental toxicity testing of petroleum substances: Application of the mouse embryonic stem cell test (EST) to compare in vitro potencies with potencies observed in vivo.

    Science.gov (United States)

    Kamelia, Lenny; Louisse, Jochem; de Haan, Laura; Rietjens, Ivonne M C M; Boogaard, Peter J

    2017-10-01

    Prenatal developmental toxicity (PDT) as observed with some petroleum substances (PS) has been associated with the presence of 3-7 ring polycyclic aromatic hydrocarbons (PAHs). In the present study, the applicability of ES-D3 cell differentiation assay of the EST to evaluate in vitro embryotoxicity potencies of PS and gas-to-liquid (GTL) products as compared to their in vivo potencies was investigated. DMSO-extracts of a range of PS, containing different amounts of PAHs, and GTL-products, which are devoid of PAHs, were tested in the ES-D3 cell proliferation and differentiation assays of the EST. The results show that PS inhibited the differentiation of ES-D3 cells into cardiomyocytes in a concentration-dependent manner at non-cytotoxic concentrations, and that their potency was proportional to their PAH content. In contrast, as expected, GTL-products did not inhibit ES-D3 cell viability or differentiation at all. The in vitro PDT potencies were compared to published in vivo PDT studies, and a good correlation was found between in vitro and in vivo results (R 2 =0.97). To conclude, our results support the hypothesis that PAHs are the primary inducers of the PDT in PS. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Evaluation of the use of various rat strains for immunogenic potency tests of Sabin-derived inactivated polio vaccines.

    Science.gov (United States)

    Someya, Yuichi; Ami, Yasushi; Takai-Todaka, Reiko; Fujimoto, Akira; Haga, Kei; Murakami, Kosuke; Fujii, Yoshiki; Shirato, Haruko; Oka, Tomoichiro; Shimoike, Takashi; Katayama, Kazuhiko; Wakita, Takaji

    2018-03-01

    Slc:Wistar rats have been the only strain used in Japan for purpose of evaluating a national reference vaccine for the Sabin-derived inactivated polio vaccine (sIPV) and the immunogenicity of sIPV-containing products. However, following the discovery that the Slc:Wistar strain was genetically related to the Fischer 344 strain, other "real" Wistar strains, such as Crlj:WI, that are available worldwide were tested in terms of their usefulness in evaluating the immunogenicity of the past and current lots of a national reference vaccine. The response of the Crlj:WI rats against the serotype 1 of sIPV was comparable to that of the Slc:Wistar rats, while the Crlj:WI rats exhibited a higher level of response against the serotypes 2 and 3. The immunogenic potency units of a national reference vaccine determined using the Slc:Wistar rats were reproduced on tests using the Crlj:WI rats. These results indicate that a titer of the neutralizing antibody obtained in response to a given dose of sIPV cannot be directly compared between these two rat strains, but that, more importantly, the potency units are almost equivalent for the two rat strains. Copyright © 2018 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  13. MATHEMATICAL MODELING FOR BENZYLPENICILIN POTASSIUM AND STREPTOMYCIN SULPHATE POTENCY DETERMINATION OF ASCOMICIN

    Directory of Open Access Journals (Sweden)

    Viviana Ciuca

    2016-12-01

    Full Text Available Ascomicin is an antibacterial unguent for treatment of local infections of skin, eyes, outer ear, in cattle, sheep, pig, dog and cat. The product contains two active substances: benzylpenicillin potassium (Penicillin G potassium and streptomycin sulphate. The main characteristic of commercial product is benzylpenicillin potassium and streptomycin sulphate potency. The potency is estimated by comparing the inhibition of growth of sensitive micro-organisms produced by known concentrations of the antibiotic to be examined and a reference substance. The validation study aims to demonstrate the determination of the potency of benzylpenicillin potassium and streptomycin sulphate, it is an appropriate analytical method, reproducible and meets the quality requirements of Ascomicin product. The paper establishes the performance characteristics of the method considered and identify the factors that influence these characteristics. The diameters of inhibition zones, directly proportional to the logarithm of the concentration of the antibiotic used for the assay, measured and calculated using statistical methods (Combistats Soft. The assay is designed in such a way that the mathematical model on which the potency equation is based can be proved to be valid. A parallel-line model is chosen. The two log dose response lines of the preparation under examination and the standard preparation are parallel; they are rectilinear over the range of doses used in the calculation. These conditions are verified by validity tests for a given probability (P = 0.05. The test is not valid unless the confidence limits (P = 0.95 are not less than 50 per cent and not more than 200 per cent of the estimated potency. The estimated potency is not less than 95 per cent and not more than 105 per cent of the stated potency. The stated potency is not less than 19400 international units/g benzylpenicillin potassium and 13960 international units/g streptomycin sulphate. The validation

  14. Preliminary study of histamine H4 receptor expressed on human CD4+ T cells and its immunomodulatory potency in the IL-17 pathway of psoriasis.

    Science.gov (United States)

    Han, Song Hee; Hur, Min Seok; Kim, Min Jung; Kim, Bo Mi; Kim, Kyoung Woon; Kim, Hae Rim; Choe, Yong Beom; Ahn, Kyu Joong; Lee, Yang Won

    2017-10-01

    Previous studies have shown the expression of histamine H 4 receptor (H4R) on CD4 + T cells, especially human CD4 + T h 2-polarized T cells. This study aimed to investigate the role of H4R on these effector T cells in psoriasis. We enrolled three patients each with active psoriasis, inactive psoriasis, scalp seborrheic dermatitis, and three normal controls, and compared the basal expression of H4R mRNA in their peripheral blood CD4 + T cells. Then, we identified H4R expression in dermal CD4 + T cells. Furthermore, we investigated H4R expression after stimulating separated peripheral blood CD4 + T cells with several inflammatory cytokines. The results showed higher H4R expression in the active psoriasis group compared to the inactive psoriasis group. It was interesting that interleukin (IL)-23, which is a representative cytokine contributing to T h 17 cell differentiation, stimulated H4R expression significantly. After adding a selective H4R antagonist (JNJ-7777120) while the CD4 + T cells were polarized into T h 17 cells, we observed a tendency toward suppressed IL-17 secretion. Histamine stimulation influences the IL-17 pathway in psoriasis via the fourth histamine receptor subtype, H4R, on CD4 + T cells. The immunomodulatory roles of H4R suggest its potency as a new therapeutic target for obstinate psoriasis. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  15. Radioprotective potency of ginseng on some haematopoietic and physiological parameters in irradiated rats

    International Nuclear Information System (INIS)

    Ashry, O.M.; Hussein, E.M.

    2007-01-01

    Currently, investigations focus on co administration of natural products with radiation treatment. The present study was assessed to investigate the potency of ginseng as a radioprotective agent on haematopoietic cell recovery, the content of reduced glutathione (GSH) and malonaldehyde (MDA) level in addition to physiological bio markers. Panax ginseng was intraperitoneally injected (100 mg/ kg) to female rats 24 h before gamma irradiation of 7 Gy which is liable to disturb the haematopoietic system and the organs involved as the bone marrow and spleen. Animals were investigated after 5 and 9 days from irradiation, ginseng or dual treatments. Irradiation caused significant wt loss of the body and spleen, decrease in bone marrow (B.M.) viable cells, significant depression in leukocytes with its differential counts, significant drop in erythrocytes, haemoglobin and haematocrite values besides elevation in MCV. Gamma-irradiation treatment resulted in significant increase in serum MDA and glucose as well as significant reduction in blood GSH. Significant elevations in transaminases (ALT and AST) and alkaline phosphatase (ALP) activities were recorded after gamma irradiation. Preservation of body wt, B.M. viable cells, spleen wt and haematopoietic cell recovery was evident upon ginseng pre-administration. It ameliorated the depression in GSH content and the elevation in MDA level. ALT, AST and ALP were depressed approaching the control level after 9 days from dual treatments and blood sugar level was maintained. The study points out the promising positive role played by ginseng as a nontoxic natural product to reduce the time necessary for reconstituting haematopoietic cells and protecting vital physiological processes after irradiation

  16. Development of quantitative structure-activity relationship (QSAR) models to predict the carcinogenic potency of chemicals

    International Nuclear Information System (INIS)

    Venkatapathy, Raghuraman; Wang Chingyi; Bruce, Robert Mark; Moudgal, Chandrika

    2009-01-01

    Determining the carcinogenicity and carcinogenic potency of new chemicals is both a labor-intensive and time-consuming process. In order to expedite the screening process, there is a need to identify alternative toxicity measures that may be used as surrogates for carcinogenic potency. Alternative toxicity measures for carcinogenic potency currently being used in the literature include lethal dose (dose that kills 50% of a study population [LD 50 ]), lowest-observed-adverse-effect-level (LOAEL) and maximum tolerated dose (MTD). The purpose of this study was to investigate the correlation between tumor dose (TD 50 ) and three alternative toxicity measures as an estimator of carcinogenic potency. A second aim of this study was to develop a Classification and Regression Tree (CART) between TD 50 and estimated/experimental predictor variables to predict the carcinogenic potency of new chemicals. Rat TD 50 s of 590 structurally diverse chemicals were obtained from the Cancer Potency Database, and the three alternative toxicity measures considered in this study were estimated using TOPKAT, a toxicity estimation software. Though poor correlations were obtained between carcinogenic potency and the three alternative toxicity (both experimental and TOPKAT) measures for the CPDB chemicals, a CART developed using experimental data with no missing values as predictor variables provided reasonable estimates of TD 50 for nine chemicals that were part of an external validation set. However, if experimental values for the three alternative measures, mutagenicity and logP are not available in the literature, then either the CART developed using missing experimental values or estimated values may be used for making a prediction

  17. In vitro and in vivo potency of insulin analogues designed for clinical use.

    Science.gov (United States)

    Vølund, A; Brange, J; Drejer, K; Jensen, I; Markussen, J; Ribel, U; Sørensen, A R; Schlichtkrull, J

    1991-11-01

    Analogues of human insulin designed to have improved absorption properties after subcutaneous injection have been prepared by recombinant DNA technology. Five rapidly absorbed analogues, being predominantly in mono- or di-meric states in the pharmaceutical preparation, and a hexameric analogue with very low solubility at neutral pH and slow absorption, were studied. Receptor binding assays with HEP-G2 cells showed overall agreement with mouse free adipocyte assays. Two analogues, B28Asp and A21Gly + B27Arg + B30Thr-NH2, had nearly the same molar in vitro potency as human insulin. Another two showed increased adipocyte potency and receptor binding, B10Asp 194% and 333% and A8His + B4His + B10Glu + B27His 575% and 511%, while B9Asp + B27Glu showed 29% and 18% and the B25Asp analogue only 0.12% and 0.05% potency. Bioassays in mice or rabbits of the analogues except B25Asp showed that they had the same in vivo potency as human insulin 1.00 IU = 6.00 nmol. Thus the variation had the same in vivo potency as human insulin 1.00 IU = 6.00 nmol. Thus the variation in in vivo potency reflects the differences in receptor binding affinity. Relative to human insulin a low concentration is sufficient for a high affinity analogue to produce a given receptor complex formation and metabolic response. In conclusion, human insulin and analogues with markedly different in vitro potencies were equipotent in terms of hypoglycaemic effect. This is in agreement with the concept that elimination of insulin from blood and its subsequent degradation is mediated by insulin receptors.

  18. Potency assay development for cellular therapy products: an ISCT review of the requirements and experiences in the industry.

    Science.gov (United States)

    Bravery, Christopher A; Carmen, Jessica; Fong, Timothy; Oprea, Wanda; Hoogendoorn, Karin H; Woda, Juliana; Burger, Scott R; Rowley, Jon A; Bonyhadi, Mark L; Van't Hof, Wouter

    2013-01-01

    The evaluation of potency plays a key role in defining the quality of cellular therapy products (CTPs). Potency can be defined as a quantitative measure of relevant biologic function based on the attributes that are linked to relevant biologic properties. To achieve an adequate assessment of CTP potency, appropriate in vitro or in vivo laboratory assays and properly controlled clinical data need to be created. The primary objective of a potency assay is to provide a mechanism by which the manufacturing process and the final product for batch release are scrutinized for quality, consistency and stability. A potency assay also provides the basis for comparability assessment after process changes, such as scale-up, site transfer and new starting materials (e.g., a new donor). Potency assays should be in place for early clinical development, and validated assays are required for pivotal clinical trials. Potency is based on the individual characteristics of each individual CTP, and the adequacy of potency assays will be evaluated on a case-by-case basis by regulatory agencies. We provide an overview of the expectations and challenges in development of potency assays specific for CTPs; several real-life experiences from the cellular therapy industry are presented as illustrations. The key observation and message is that aggressive early investment in a solid potency evaluation strategy can greatly enhance eventual CTP deployment because it can mitigate the risk of costly product failure in late-stage development. Copyright © 2013. Published by Elsevier Inc.

  19. The Relative Potency of Inverse Opioid Agonists and a Neutral Opioid Antagonist in Precipitated Withdrawal and Antagonism of Analgesia and Toxicity

    OpenAIRE

    Sirohi, Sunil; Dighe, Shveta V.; Madia, Priyanka A.; Yoburn, Byron C.

    2009-01-01

    Opioid antagonists can be classified as inverse agonists and neutral antagonists. In the opioid-dependent state, neutral antagonists are significantly less potent in precipitating withdrawal than inverse agonists. Consequently, neutral opioid antagonists may offer advantages over inverse agonists in the management of opioid overdose. In this study, the relative potency of three opioid antagonists to block opioid analgesia and toxicity and precipitate withdrawal was exa...

  20. Response surface methodology to simplify calculation of wood energy potency from tropical short rotation coppice species

    Science.gov (United States)

    Haqiqi, M. T.; Yuliansyah; Suwinarti, W.; Amirta, R.

    2018-04-01

    Short Rotation Coppice (SRC) system is an option to provide renewable and sustainable feedstock in generating electricity for rural area. Here in this study, we focussed on application of Response Surface Methodology (RSM) to simplify calculation protocols to point out wood chip production and energy potency from some tropical SRC species identified as Bauhinia purpurea, Bridelia tomentosa, Calliandra calothyrsus, Fagraea racemosa, Gliricidia sepium, Melastoma malabathricum, Piper aduncum, Vernonia amygdalina, Vernonia arborea and Vitex pinnata. The result showed that the highest calorific value was obtained from V. pinnata wood (19.97 MJ kg-1) due to its high lignin content (29.84 %, w/w). Our findings also indicated that the use of RSM for estimating energy-electricity of SRC wood had significant term regarding to the quadratic model (R2 = 0.953), whereas the solid-chip ratio prediction was accurate (R2 = 1.000). In the near future, the simple formula will be promising to calculate energy production easily from woody biomass, especially from SRC species.

  1. First systematic evaluation of the potency of Cannabis sativa plants grown in Albania.

    Science.gov (United States)

    Bruci, Zana; Papoutsis, Ioannis; Athanaselis, Sotirios; Nikolaou, Panagiota; Pazari, Ermira; Spiliopoulou, Chara; Vyshka, Gentian

    2012-10-10

    Cannabis products (marijuana, hashish, cannabis oil) are the most frequently abused illegal substances worldwide. Delta-9-tetrahydrocannabinol (THC) is the main psychoactive component of Cannabis sativa plant, whereas cannabidiol (CBD) and cannabinol (CBN) are other major but no psychoactive constituents. Many studies have already been carried out on these compounds and chemical research was encouraged due to the legal implications concerning the misuse of marijuana. The aim of this study was to determine THC, CBD and CBN in a significant number of cannabis samples of Albanian origin, where cannabis is the most frequently used drug of abuse, in order to evaluate and classify them according to their cannabinoid composition. A GC-MS method was used, in order to assay cannabinoid content of hemp samples harvested at different maturation degree levels during the summer months and grown in different areas of Albania. This method can also be used for the determination of plant phenotype, the evaluation of psychoactive potency and the control of material quality. The highest cannabinoid concentrations were found in the flowers of cannabis. The THC concentrations in different locations of Albania ranged from 1.07 to 12.13%. The influence of environmental conditions on cannabinoid content is discussed. The cannabinoid content of cannabis plants were used for their profiling, and it was used for their classification, according to their geographical origin. The determined concentrations justify the fact that Albania is an area where cannabis is extensively cultivated for illegal purposes. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. The human skin/chick chorioallantoic membrane model accurately predicts the potency of cosmetic allergens.

    Science.gov (United States)

    Slodownik, Dan; Grinberg, Igor; Spira, Ram M; Skornik, Yehuda; Goldstein, Ronald S

    2009-04-01

    The current standard method for predicting contact allergenicity is the murine local lymph node assay (LLNA). Public objection to the use of animals in testing of cosmetics makes the development of a system that does not use sentient animals highly desirable. The chorioallantoic membrane (CAM) of the chick egg has been extensively used for the growth of normal and transformed mammalian tissues. The CAM is not innervated, and embryos are sacrificed before the development of pain perception. The aim of this study was to determine whether the sensitization phase of contact dermatitis to known cosmetic allergens can be quantified using CAM-engrafted human skin and how these results compare with published EC3 data obtained with the LLNA. We studied six common molecules used in allergen testing and quantified migration of epidermal Langerhans cells (LC) as a measure of their allergic potency. All agents with known allergic potential induced statistically significant migration of LC. The data obtained correlated well with published data for these allergens generated using the LLNA test. The human-skin CAM model therefore has great potential as an inexpensive, non-radioactive, in vivo alternative to the LLNA, which does not require the use of sentient animals. In addition, this system has the advantage of testing the allergic response of human, rather than animal skin.

  3. Environmental levels and toxicological potencies of a novel mixed halogenated carbazole

    Directory of Open Access Journals (Sweden)

    Miren Pena-Abaurrea

    2016-09-01

    Full Text Available The present work involves an extensive analytical and toxicological description of a recently identified mixed halogenated carbazole found in sediment samples, 1,8-dibromo-3,6-dichloro-9H-carbazole (BCCZ. Concentrations and the relative effect potency (REP were calculated for the target BCCZ in a set of stream sediments collected in 2008 in Ontario, Canada. The levels calculated for BCCZ as compared to those previously assessed for legacy persistent organic pollutants (POPs in the same samples revealed a significant contribution of BCCZ to the total organic chemical contamination (<1%–95%; average 37%. The corresponding dioxin toxic equivalencies (TEQs of BCCZ in the sediment extracts were estimated from experimental REP data. The experimental data presented supports the classification of this emerging halogenated chemical as a contaminant of emerging environmental concern. Although potential emission sources could not be identified, this study highlights the importance of on-going research for complete characterization of halogenated carbazoles and related compounds.

  4. Drug binding affinities and potencies are best described by a log-normal distribution and use of geometric means

    International Nuclear Information System (INIS)

    Stanisic, D.; Hancock, A.A.; Kyncl, J.J.; Lin, C.T.; Bush, E.N.

    1986-01-01

    (-)-Norepinephrine (NE) is used as an internal standard in their in vitro adrenergic assays, and the concentration of NE which produces a half-maximal inhibition of specific radioligand binding (affinity; K/sub I/), or half-maximal contractile response (potency; ED 50 ) has been measured numerous times. The goodness-of-fit test for normality was performed on both normal (Gaussian) or log 10 -normal frequency histograms of these data using the SAS Univariate procedure. Specific binding of 3 H-prazosin to rat liver (α 1 -), 3 H rauwolscine to rat cortex (α 2 -) and 3 H-dihydroalprenolol to rat ventricle (β 1 -) or rat lung (β 2 -receptors) was inhibited by NE; the distributions of NE K/sub I/'s at all these sites were skewed to the right, with highly significant (p 50 's of NE in isolated rabbit aorta (α 1 ), phenoxybenzamine-treated dog saphenous vein (α 2 ) and guinea pig atrium (β 1 ). The vasorelaxant potency of atrial natriuretic hormone in histamine-contracted rabbit aorta also was better described by a log-normal distribution, indicating that log-normalcy is probably a general phenomenon of drug-receptor interactions. Because data of this type appear to be log-normally distributed, geometric means should be used in parametric statistical analyses

  5. Luteinizing hormone reduction by the male potency herb, Butea superba Roxb.

    Directory of Open Access Journals (Sweden)

    S. Malaivijitnond

    2010-09-01

    Full Text Available To determine if Butea superba Roxb., a traditional Thai male potency herb, has androgenic activity in 60-day-old male Wistar rats, we measured its effects on the pituitary-testicular axis and sex organs. Intact and orchidectomized adult male rats were subdivided into five groups (10 rats/group: distilled water, Butea superba (BS-10, BS-50, BS-250, and testosterone propionate (TP. They received 0, 10, 50, and 250 mg·kg body weight-1·day-1 BS in distilled water by gavage and 6 mg·kg body weight-1·day-1 TP sc, respectively, during the 30-day treatment period. Blood was collected every 15 days and luteinizing hormone (LH, follicle-stimulating hormone (FSH and testosterone were measured. Changes of weight and histological appearance of sex organs were determined at the end of the 30-day treatment and 15-day post-treatment periods. TP treatment reduced serum FSH and LH levels and significantly increased the weight of the seminal vesicles and epididymis, in accordance with histopathological changes, in both intact and orchidectomized rats. No changes in serum testosterone, LH, and FSH levels were observed in any of the intact rats treated with BS, but a significant increase in seminal vesicle weight was observed only in the BS-250 group. Although a significant reduction in serum LH was detected in the BS-50 and BS-250 groups of orchidectomized rats, no significant change in weight or histology of sex organs was observed. Thus, we conclude that B. superba needs endogenous testosterone to work synergistically to stimulate the accessory sex organ of intact animals and can potentially exhibit an LH reduction effect in orchidectomized animals.

  6. Fate and antibacterial potency of anticoccidial drugs and their main abiotic degradation products

    International Nuclear Information System (INIS)

    Hansen, Martin; Krogh, Kristine A.; Brandt, Asbjorn; Christensen, Jan H.; Halling-Sorensen, Bent

    2009-01-01

    The antibacterial potency of eight anticoccidial drugs was tested in a soil bacteria bioassay (pour plate method), EC 50 -values between 2.4 and 19.6 μM were obtained; however, one compound, nicarbazin exhibited an EC 50 -value above the maximum tested concentration (21 μM, 9.1 mg L -1 ). The potency of mixtures of two of the compounds, narasin and nicarbazin, was synergistic (more than additive) with 10-fold greater antibacterial potency of the mixture than can be explained by their individual EC 50 -values. The influence of pH, temperature, oxygen concentration and light on the transformation of robenidine and salinomycin was investigated. Robenidine was transformed by photolysis (DT 50 of 4.1 days) and was unstable at low pH (DT 50 of approximately 4 days); salinomycin was merely transformed at low pH, the latter into an unknown number of products. The antibacterial potency of the mixtures of transformation products of robenidine after photolysis and at low pH was comparable with that of the parent compound. Finally five photo-transformation products of robenidine were structural elucidated by accurate mass measurements, i-FIT values (isotopic pattern fit) and MS/MS fragmentation patterns. - Five photo-transformation products of robenidine were structural elucidated. This mixture was found to have similar antibacterial potency as the parent compound

  7. The local lymph node assay and the assessment of relative potency: status of validation.

    Science.gov (United States)

    Basketter, David A; Gerberick, Frank; Kimber, Ian

    2007-08-01

    For the prediction of skin sensitization potential, the local lymph node assay (LLNA) is a fully validated alternative to guinea-pig tests. More recently, information from LLNA dose-response analyses has been used to assess the relative potency of skin sensitizing chemicals. These data are then deployed for risk assessment and risk management. In this commentary, the utility and validity of these relative potency measurements are reviewed. It is concluded that the LLNA does provide a valuable assessment of relative sensitizing potency in the form of the estimated concentration of a chemical required to produce a threefold stimulation of draining lymph node cell proliferation compared with concurrent controls (EC3 value) and that all reasonable validation requirements have been addressed successfully. EC3 measurements are reproducible in both intra- and interlaboratory evaluations and are stable over time. It has been shown also, by several independent groups, that EC3 values correlate closely with data on relative human skin sensitization potency. Consequently, the recommendation made here is that LLNA EC3 measurements should now be regarded as a validated method for the determination of the relative potency of skin sensitizing chemicals, a conclusion that has already been reached by a number of independent expert groups.

  8. Fate and antibacterial potency of anticoccidial drugs and their main abiotic degradation products

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, Martin [Section of Toxicology and Environmental Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen (Denmark)], E-mail: mah@farma.ku.dk; Krogh, Kristine A. [Section of Toxicology and Environmental Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen (Denmark); Brandt, Asbjorn [Section of Veterinary Medicines, Danish Medicines Agency, Axel Heides Gade 1, DK-2300 Copenhagen (Denmark); Christensen, Jan H. [Section of Soil and Environmental Chemistry, Department of Basic Sciences and Environment, Faculty of Life Sciences, University of Copenhagen, Thorvaldsensvej 40, DK-1871 Frederiksberg (Denmark); Halling-Sorensen, Bent [Section of Toxicology and Environmental Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen (Denmark)

    2009-02-15

    The antibacterial potency of eight anticoccidial drugs was tested in a soil bacteria bioassay (pour plate method), EC{sub 50}-values between 2.4 and 19.6 {mu}M were obtained; however, one compound, nicarbazin exhibited an EC{sub 50}-value above the maximum tested concentration (21 {mu}M, 9.1 mg L{sup -1}). The potency of mixtures of two of the compounds, narasin and nicarbazin, was synergistic (more than additive) with 10-fold greater antibacterial potency of the mixture than can be explained by their individual EC{sub 50}-values. The influence of pH, temperature, oxygen concentration and light on the transformation of robenidine and salinomycin was investigated. Robenidine was transformed by photolysis (DT{sub 50} of 4.1 days) and was unstable at low pH (DT{sub 50} of approximately 4 days); salinomycin was merely transformed at low pH, the latter into an unknown number of products. The antibacterial potency of the mixtures of transformation products of robenidine after photolysis and at low pH was comparable with that of the parent compound. Finally five photo-transformation products of robenidine were structural elucidated by accurate mass measurements, i-FIT values (isotopic pattern fit) and MS/MS fragmentation patterns. - Five photo-transformation products of robenidine were structural elucidated. This mixture was found to have similar antibacterial potency as the parent compound.

  9. Potency of fibrolytic bacteria isolated from Indonesian sheep's colon ...

    African Journals Online (AJOL)

    USER

    2010-05-17

    May 17, 2010 ... straw meal (2 mm in size) + 7 ml dairy cattle feces and 28 ml .... This publication is part of Competitive Grant Research funded by Directorate of Higher Education, Ministry of. National Education Republic of Indonesia.

  10. Investigation of landfill leachate toxic potency: An integrated approach with the use of stress indices in tissues of mussels

    Energy Technology Data Exchange (ETDEWEB)

    Tsarpali, Vasiliki [Section of Animal Biology, Department of Biology, Faculty of Sciences, University of Patras, 26500 Patras (Greece); Dailianis, Stefanos, E-mail: sdailianis@upatras.gr [Section of Animal Biology, Department of Biology, Faculty of Sciences, University of Patras, 26500 Patras (Greece)

    2012-11-15

    Highlights: Black-Right-Pointing-Pointer Leachate induces mortality of mussels and their cell death at very low doses. Black-Right-Pointing-Pointer Prepathological alterations occur in tissues of leachate-exposed mussels. Black-Right-Pointing-Pointer Alterations of stress indices reveal neurotoxic and genotoxic potency of leachate. Black-Right-Pointing-Pointer Leachate could induce oxidative damage in tissues of leachate-exposed mussels. - Abstract: The present study investigates the harmful impacts of landfill leachate release and/or disposal into the marine environment, as well as its ability to induce lethal and pre-pathological alterations in marine organisms, such as the mussel Mytilus galloprovincialis. In specific, mortality test (96 h), performed first in order to estimate leachate lethal endpoints, showed increased levels of mussel mortality after exposure to leachate higher than 0.5%, v/v (96 h LC{sub 50} = 0.526%, v/v), while the exposure to 0.01 and 0.1% (v/v) of leachate showed negligible levels of mortality (96 h LC{sub 10} = 0.167%, v/v). Furthermore, the estimation of lysosomal membrane integrity in hemocytes of exposed mussels (Neutral Red Retention Time assay) showed increased levels of lysosomal destabilization in cells of mussels exposed to sub-lethal concentrations of leachate (0.01, 0.1 and 0.5%, v/v) for 4 days. In order to exclude parameters, such as mussel mortality and cell death, which could interfere with the obtained results, leachate at final concentrations of 0.01 and 0.1% (v/v) were finally used for the estimation of a battery of stress indices in target tissues of mussels, such as hemolymph, gills and digestive gland. According to the results, leachate-exposed mussels showed a significant inhibition of acetylcholinesterase activity, increased levels of nuclear abnormalities, as well as increased levels of metallothionein, superoxide anion and lipid peroxides (in terms of malondialdehyde equivalents) in each tissue tested. The

  11. Higher Education

    African Journals Online (AJOL)

    Kunle Amuwo: Higher Education Transformation: A Paradigm Shilt in South Africa? ... ty of such skills, especially at the middle management levels within the higher ... istics and virtues of differentiation and diversity. .... may be forced to close shop for lack of capacity to attract ..... necessarily lead to racial and gender equity,.

  12. Hydraphiles enhance antimicrobial potency against Escherichia coli, Pseudomonas aeruginosa, and Bacillus subtilis.

    Science.gov (United States)

    Patel, Mohit B; Garrad, Evan C; Stavri, Ariel; Gokel, Michael R; Negin, Saeedeh; Meisel, Joseph W; Cusumano, Zachary; Gokel, George W

    2016-06-15

    Hydraphiles are synthetic amphiphiles that form ion-conducting pores in liposomal membranes. These pores exhibit open-close behavior when studied by planar bilayer conductance techniques. In previous work, we showed that when co-administered with various antibiotics to the DH5α strain of Escherichia coli, they enhanced the drug's potency. We report here potency enhancements at low concentrations of hydraphiles for the structurally and mechanistically unrelated antibiotics erythromycin, kanamycin, rifampicin, and tetracycline against Gram negative E. coli (DH5α and K-12) and Pseudomonas aeruginosa, as well as Gram positive Bacillus subtilis. Earlier work suggested that potency increases correlated to ion transport function. The data presented here comport with the function of hydraphiles to enhance membrane permeability in addition to, or instead of, their known function as ion conductors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Polycyclic Aromatic Hydrocarbons in Air and their Toxic Potency

    Indian Academy of Sciences (India)

    to have additive or synergistic effects with other PAH mixtures and with other ... PAH in fossil fuels has concluded that pyrolysis of organic materials even at ..... invertebrates and fish can be many times higher than the con- tent of the PAR in ...

  14. In ova angiogenesis analgesic and anti inflammatory potency of Aerva monsoniae (Amaranthaceae

    Directory of Open Access Journals (Sweden)

    Sandhya S

    2012-10-01

    Full Text Available Objective: To evaluate the wound healing potency of aqueous extract of Aerva monsoniae (A. monsoniae by in vitro method using fertilized eggs, in vivo analgesic and anti inflammatory activity in rodents and the anti bacterial activity on the bacterial strains that infect the wound. Methods: The whole plant of A. monsoniae was extracted with water and then subjected to preliminary chemical screening. It was then evaluated for in ova angiogenesis on fertilized white leg horn eggs using the concentrations of 200-600 毺 g/mL. The analgesic activity was evaluated in mice using the dose 100 and 250 mg/kg. The anti inflammatory activity was evaluated in rats using the dose 250 mg/kg and 500 mg/kg. In both the parameters water was used as the control and diclofenac was used the standard. The anti bacterial activity on Staphylococcus aureus and Pseudomonas aerugenosa was performed. Results: The phytochemical screening revealed the presence of tannins, flavonoids and saponins. The in ova angiogenesis revealed a dose dependent activity which proves the wound healing claim of the plant as more number of blood capillaries were formed at the site of the drug. The plant proved to be a potent analgesic and anti inflammatory agent at doses 1 00 mg/kg and 250 mg/kg. The anti bacterial activity was present but at higher doses. Conclusions: The parameters studied in the present investigation proved that the plant is a potent wound healer. Further in vivo wound healing studies on animal model is desired. As the extract showed potent analgesic, anti inflammatory and anti bacterial properties, it can be considered that when formulated into suitable formulation, and it can reduce the pain, inflammation and infections related to wound very well.

  15. Extracellular Ca(2+)-dependent enhancement of cytocidal potency of zoledronic acid in human oral cancer cells.

    Science.gov (United States)

    Inoue, Sayaka; Arai, Naoya; Tomihara, Kei; Takashina, Michinori; Hattori, Yuichi; Noguchi, Makoto

    2015-08-15

    Direct antitumor effects of bisphosphonates (BPs) have been demonstrated in various cancer cells in vitro. However, the effective concentrations of BPs are typically much higher than their clinically relevant concentrations. Oral cancers frequently invade jawbone and may lead to the release of Ca(2+) in primary lesions. We investigated the effects of the combined application of zoledronic acid (ZA) and Ca(2+) on proliferation and apoptosis of oral cancer cells. Human oral cancer cells, breast cancer cells, and colon cancer cells were treated with ZA at a wide range of concentrations in different Ca(2+) concentration environments. Under a standard Ca(2+) concentration (0.6mM), micromolar concentrations of ZA were required to inhibit oral cancer cell proliferation. Increasing extracellular Ca(2+) concentrations greatly enhanced the potency of the ZA cytocidal effect. The ability of Ca(2+) to enhance the cytocidal effects of ZA was negated by the Ca(2+)-selective chelator EGTA. In contrast, the cytocidal effect of ZA was less pronounced in breast and colon cancer cells regardless of whether extracellular Ca(2+) was elevated. In oral cancer cells incubated with 1.6mM Ca(2+), ZA up-regulated mitochondrial Bax expression and increased mitochondrial Ca(2+) uptake. This was associated with decreased mitochondrial membrane potential and increased release of cytochrome c. We suggest that ZA can specifically produce potent cytocidal activity in oral cancer cells in an extracellular Ca(2+)-dependent manner, implying that BPs may be useful for treatment of oral squamous cell carcinoma with jawbone invasion leading to the hypercalcemic state. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. The spermicidal potency of Coca-Cola and Pepsi-Cola.

    Science.gov (United States)

    Hong, C Y; Shieh, C C; Wu, P; Chiang, B N

    1987-09-01

    The inhibitory effect of Old Coke, caffeine-free New Coke, New Coke, Diet Coke and Pepsi-Cola on human sperm motility was studied with a trans-membrane migration method. None of them could decrease sperm motility to less than 70% of control within one hour. A previous study which claimed a marked variation of spermicidal potencies among different formulations of Coca-Cola could not be confirmed. Even if cola has a spermicidal effect, its potency is relatively weak as compared with other well-known spermicidal agents.

  17. Higher Education

    Science.gov (United States)

    & Development (LDRD) National Security Education Center (NSEC) Office of Science Programs Richard P Databases National Security Education Center (NSEC) Center for Nonlinear Studies Engineering Institute Scholarships STEM Education Programs Teachers (K-12) Students (K-12) Higher Education Regional Education

  18. A comparison of the relative antioxidant potency of L-ergothioneine and idebenone.

    Science.gov (United States)

    Dong, Kelly K; Damaghi, Niusha; Kibitel, Jeannie; Canning, Matthew T; Smiles, Kenneth A; Yarosh, Daniel B

    2007-09-01

    L-ergothioneine (EGT) is a stable antioxidant found in food plants as well as in animal tissue undergoing relatively high levels of oxidative stress. Idebenone is a stable analog of the antioxidant coenzyme Q(10). All are potent antioxidants found in skincare products, but their relative potencies are not well described. To establish the physiological relevance of EGT by examining transcription of the EGT transporter gene OCTN-1 and production of the receptor protein in skin fibroblasts. In addition, to compare the inhibition of lipid peroxide formation by coenzyme Q(10) and EGT. Furthermore, to compare the peroxide-scavenging abilities of EGT and idebenone in both simple solution and in cell cultures exposed to ultraviolet A (UVA). OCTN-1 expression and production in cultured fibroblasts were measured through real-time reverse transcription-PCR and Western blotting, respectively. Alloxan-induced lipid peroxidation in liposomes was used to evaluate the inhibition of lipid peroxide formation. The abilities of EGT and idebenone to directly scavenge hydroxyl radicals produced by H(2)O(2 )were determined. Finally, we irradiated fibroblasts with UVA340 radiation and compared antioxidant capabilities to scavenge free radicals. We found that OCTN-1 is expressed and readily detectable in cultured human fibroblasts. EGT was more efficient in inhibiting lipid peroxide formation than coenzyme Q(10) or idebenone. Samples treated with EGT had significantly less peroxide than those treated with idebenone 120 min after adding the antioxidants to H(2)O(2). EGT acted significantly quicker and more efficiently in capturing reactive oxygen species (ROS) after UVA340 irradiation. EGT is a natural skin antioxidant, as evidenced by the presence of the EGT transporter in fibroblasts. EGT is a more powerful antioxidant than either coenzyme Q(10) or idebenone due to its relatively greater efficiency in directly scavenging free radicals and in protecting cells from UV-induced ROS.

  19. Antimicrobial, Cytotoxic and Phytotoxic Potency of Ethyl Acetate ...

    African Journals Online (AJOL)

    The antifungal activity was determined by inhibitory effect on the growth of. Alternaria ... Results: The extract showed phytotoxic activity (at 95% level of significance) against Lemna minor ..... screening of various organic extracts of caesalpinia.

  20. Higher Education.

    Science.gov (United States)

    Hendrickson, Robert M.

    This chapter reports 1982 cases involving aspects of higher education. Interesting cases noted dealt with the federal government's authority to regulate state employees' retirement and raised the questions of whether Title IX covers employment, whether financial aid makes a college a program under Title IX, and whether sex segregated mortality…

  1. Glycemic potency of muffins made with wheat, rice, corn, oat and barley flours: a comparative study between in vivo and in vitro.

    Science.gov (United States)

    Soong, Yean Yean; Quek, Rina Yu Chin; Henry, Christiani Jeyakumar

    2015-12-01

    Muffins made with wheat flour are a popular snack consumed in western and emerging countries. This study aimed to examine the content of amylose, glycemic response (GR) and glycemic index (GI) of muffins baked with refined wheat and rice flours, as well as wholegrain corn, oat and barley flours. This study adopted a randomized, controlled, crossover, non-blind design. Twelve healthy participants consumed wheat, rice, corn, oat and barley muffins once and the reference glucose solution three times in a random order on non-consecutive day. Capillary blood samples were taken every 15 min in the first 60 min and every 30 min for the remaining 60 min for blood glucose analysis. The Megazyme amylose/amylopectin assay procedure was employed to measure amylose content. The GR elicited from the consumption of wheat, rice and corn muffins was comparable between these samples but significantly greater when compared with oat and barley muffins. Consumption of wholegrain muffins, apart from corn muffin, blunted postprandial GR when compared with muffins baked with refined cereal flours. Muffins baked with wheat, rice, corn, oat and barley flours gave rise to GI values of 74, 79, 74, 53 and 55, respectively. The content of amylose was significantly higher in corn, oat and barley muffins than wheat and rice muffins. The greater content of amylose and fibre may play a part in the reduced glycemic potency of oat and barley muffins. Wheat flour can be substituted with oat and barley flours for healthier muffins and other bakery products.

  2. Bioactive potency of epidermal mucus extracts from greasy grouper, Epinephelus tauvina (Forsskal, 1775

    Directory of Open Access Journals (Sweden)

    Ganesh Manikantan

    2016-07-01

    Full Text Available Objective: To study the bio-potency of epidermal mucus from Epinephelus tauvina. Methods: Mucus was extracted with acidic, organic and aqueous solvents. Protein, carbohydrate, lipid, amino acid and fatty acid content of mucus extracts were quantified by UV-spectrophotometer, high performance liquid chromatography and gas chromatographymass spectrometer, respectively. Antimicrobial activity was tested against five human and fish pathogens by using agar well diffusion method. The molecular weight of peptides was determined using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The haemolytic activity of extracts was tested against chick, goat, cow and human red blood cell. Results: Protein contributed with maximum of 26.25% in crude mucus. Arginine was recorded maximum of (133.9 nmol/mL in crude mucus. 2,4,6-Decatrienoic acid and bis (a-chloroethyl sulfone were confirmed in organic extract. The antimicrobial activity of acidic extract was significant. Among the human pathogens, maximum zone of inhibition [(26.0 ± 0.3 mm] was observed against Proteus mirabilis. Whereas, among fish pathogens maximum zone of inhibition [(25.0 ± 0.1 mm] was observed against Vibrio parahemolyticus. The activity of other two extracts was not remarkable. The molecular weight of peptides ranged from 115.5– 37.1 kDa in acidic extract was determined. Chicken and goat blood were found to be highly vulnerable to the lysis. Conclusions: The whole mucus could be a promising source with numerous bioactivepotency. Consequently, this preliminary information suggested that mucus is a source of novel antimicrobial agents for fish and human health related applications.

  3. An epidermal equivalent assay for identification and ranking potency of contact sensitizers

    NARCIS (Netherlands)

    Gibbs, S.; Corsini, E.; Spiekstra, S.W.; Galbiati, V.; Fuchs, H.W.; Degeorge, G.; Troese, M.; Hayden, P.; Deng, W.; Roggen, E.

    2013-01-01

    The purpose of this study was to explore the possibility of combining the epidermal equivalent (EE) potency assay with the assay which assesses release of interleukin-18 (IL-18) to provide a single test for identification and classification of skin sensitizing chemicals, including chemicals of low

  4. Single-cell entropy for accurate estimation of differentiation potency from a cell's transcriptome

    Science.gov (United States)

    Teschendorff, Andrew E.; Enver, Tariq

    2017-01-01

    The ability to quantify differentiation potential of single cells is a task of critical importance. Here we demonstrate, using over 7,000 single-cell RNA-Seq profiles, that differentiation potency of a single cell can be approximated by computing the signalling promiscuity, or entropy, of a cell's transcriptome in the context of an interaction network, without the need for feature selection. We show that signalling entropy provides a more accurate and robust potency estimate than other entropy-based measures, driven in part by a subtle positive correlation between the transcriptome and connectome. Signalling entropy identifies known cell subpopulations of varying potency and drug resistant cancer stem-cell phenotypes, including those derived from circulating tumour cells. It further reveals that expression heterogeneity within single-cell populations is regulated. In summary, signalling entropy allows in silico estimation of the differentiation potency and plasticity of single cells and bulk samples, providing a means to identify normal and cancer stem-cell phenotypes. PMID:28569836

  5. Observations of the effect of atmospheric processes on the genotoxic potency of airborne particulate matter

    DEFF Research Database (Denmark)

    Feilberg, Anders; Nielsen, Torben; Binderup, Mona-Lise

    2002-01-01

    In this study, the relationship between genotoxic potency and the occurrence of polycyclic aromatic hydrocarbons (PAH), including benzo(a)pyrene (BaP), and nitro-PAH in urban and semi-rural air masses has been investigated. The Salmonella/microsome assay has been used as a measure of genotoxic po...

  6. Collaborative study for the validation of alternative in vitro potency assays for human tetanus immunoglobulins.

    Science.gov (United States)

    Gross, S; Janssen, S W J; de Vries, B; Terao, E; Daas, A; Buchheit, K-H

    2010-07-01

    An international collaborative study to validate 2 alternative in vitro methods for the potency testing of human tetanus immunoglobulin products was organised by the European Directorate for the Quality of Medicines & HealthCare (EDQM). The study, run in the framework of the Biological Standardisation Programme (BSP) under the aegis of the European Commission and the Council of Europe, involved 21 official medicines control and industry laboratories from 15 countries. Both methods, an enzyme-linked immunoassay (EIA) and a toxoid inhibition assay (TIA), showed good reproducibility, repeatability and precision. EIA and TIA discriminated between low, medium and high potency samples. Potency estimates correlated well and both values were in close agreement with those obtained by in vivo methods. Moreover, these alternative methods allowed to resolve discrepant results between laboratories that were due to product potency loss and reporting errors. The study demonstrated that EIA and TIA are suitable quality control methods for tetanus immunoglobulin, which can be standardised in a control laboratory using a quality assurance system. Consequently, the Group of Experts on Human Blood and Blood Products of the European Pharmacopoeia revised the monograph on human tetanus immunoglobulins to include both the methods as compendial alternatives to the in vivo mouse challenge assay. 2010 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.

  7. 75 FR 8937 - Development of a Relative Potency Factor (RPF) Approach for Polycyclic Aromatic Hydrocarbon (PAH...

    Science.gov (United States)

    2010-02-26

    ... Relative Potency Factor (RPF) Approach for Polycyclic Aromatic Hydrocarbon (PAH) Mixtures AGENCY... Aromatic Hydrocarbon (PAH) Mixtures'' (EPA/635/R-08/012A). The draft document was prepared by the National... 27, 2010. The listening session on the draft document for PAH mixtures will be held on April 7, 2010...

  8. Stereoselective potencies and relative toxicities of y-Coniceine and N-Methylconiine enantiomers

    Science.gov (United States)

    '-Coniceine, coniine, and N-methylconiine are toxic alkaloids present in poison hemlock (Conium maculatum). We previously reported the comparison of the relative potencies of (+)- and (-)-coniine enantiomers. In this study, we synthesized '-coniceine and the enantiomers of N-methylconiine and dete...

  9. Validation of self-reported cannabis dose and potency: an ecological study

    NARCIS (Netherlands)

    van der Pol, P.; Liebregts, N.; de Graaf, R.; Korf, D.J.; van den Brink, W.; van Laar, M.

    2013-01-01

    Aims To assess the reliability and validity of self-reported cannabis dose and potency measures. Design Cross-sectional study comparing self-reports with objective measures of amount of cannabis and delta-9-tetrahydrocannabinol (THC) concentration. Setting Ecological study with assessments at

  10. Validation of self-reported cannabis dose and potency: an ecological study

    NARCIS (Netherlands)

    van der Pol, Peggy; Liebregts, Nienke; de Graaf, Ron; Korf, Dirk J.; van den Brink, Wim; van Laar, Margriet

    2013-01-01

    To assess the reliability and validity of self-reported cannabis dose and potency measures. Cross-sectional study comparing self-reports with objective measures of amount of cannabis and delta-9-tetrahydrocannabinol (THC) concentration. Ecological study with assessments at participants' homes or in

  11. Studies on the potency of oral polio vaccine using RD cell line and ...

    African Journals Online (AJOL)

    Studies on the potency of oral polio vaccine using RD cell line and evaluation of growth using different serum concentration and volume of media. ... The culture flasks containing different volumes of growth medium with 10% serum concentration such as 8, 9, 10, 11 and 12 ml were added to a series of culture flasks. All the ...

  12. Novel view on predicting acute toxicity: Decomposing toxicity data in species vulnerability and chemical potency.

    NARCIS (Netherlands)

    Jager, D.T.; Posthuma, L.; Zwart, D.D.; van de Meent, D.

    2007-01-01

    Chemical risk assessment usually applies empirical methods to predict toxicant effects on different species. We propose a more mechanism-oriented approach, and introduce a method to decompose toxicity data in a contribution from the chemical (potency) and from the exposed species (vulnerability). We

  13. Cold chain facility status and the potency of animal rabies vaccine ...

    African Journals Online (AJOL)

    Rabies vaccine failures were reported in literature. Realising that rabies vaccine is sensitive to temperature change, there is need to assess the storage condition of rabies vaccine from distribution centres to veterinary clinics where they are used. This is to establish the sustained potency from source to use. Cold-Chain ...

  14. Allergic contact dermatitis: A commentary on the relationship between T lymphocytes and skin sensitising potency

    International Nuclear Information System (INIS)

    Kimber, Ian; Maxwell, Gavin; Gilmour, Nicky; Dearman, Rebecca J.; Friedmann, Peter S.; Martin, Stefan F.

    2012-01-01

    T lymphocytes mediate skin sensitisation and allergic contact dermatitis. Not unexpectedly, therefore, there is considerable interest in the use of T lymphocyte-based assays as alternative strategies for the identification of skin sensitising chemicals. However, in addition to accurate identification of hazards the development of effective risk assessments requires that information is available about the relative skin sensitising potency of contact allergens. The purpose of this article is to consider the relationships that exist between the characteristics of T lymphocyte responses to contact allergens and the effectiveness/potency of sensitisation. We propose that there are 3 aspects of T lymphocyte responses that have the potential to impact on the potency of sensitisation. These are: (a) the magnitude of response, and in particular the vigour and duration of proliferation and the clonal expansion of allergen-reactive T lymphocytes, (b) the quality of response, including the balance achieved between effector and regulatory cells, and (c) the breadth of response and the clonal diversity of T lymphocyte responses. A case is made that there may be opportunities to exploit an understanding of T lymphocyte responses to contact allergens to develop novel paradigms for predicting skin sensitising potency and new approaches to risk assessment.

  15. In vitro screening of the endocrine disrupting potency of brominated flame retardants and their metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Hamers, T.; Kamstra, J.H. [Inst. for Environmental Studies (IVM), Amsterdam (Netherlands); Sonneveld, E. [BioDetection Systems (BDS), Amsterdam (Netherlands); Murk, A.J. [Wageningen Univ., Toxicology Group, Wageningen (Netherlands); Zegers, B.N.; Boon, J.P. [Royal Netherlands Inst. for Sea Research (NIOZ), Den Burg (Netherlands); Brouwer, A. [Umea Univ., Umea (Sweden)

    2004-09-15

    Substantial evidence is recently becoming available that brominated flame retardants (BFRs) are potential endocrine disruptors. The toxicological profile of BFRs, however, is too incomplete and insufficient to perform human and ecological risk assessment. To fill these gaps, the EU funded research program FIRE was started in December 2002. This program aims at the identification and toxicological characterization of the most potent and environmentally relevant BFRs and their possible risk for human and wildlife health. As part of a hazard identification approach, twenty seven BFRs have been selected within the framework of FIRE for pre-screening their endocrinedisrupting potencies. Selection of test compounds was based on a maximal variation in physicochemical characteristics of BFRs within the test set, allowing the establishment of quantitative structure-activity relationships (QSARs). In addition, environmental relevance (e.g. high production volumes and persistence) and availability for testing were used as selection criteria. BFRs were tested in seven different in vitro bioassays for their potency to interfere via estrogenic, thyroidal, androgenic, progestagenic, and Ah-receptor mediated pathways. Metabolisation rates of BFRs were determined using phenobarbital-induced rat liver microsomes. Finally, the endocrine disrupting potency of the metabolites was determined in the same in vitro bio-assays and compared to the potency of the parent compounds.

  16. Complementary three-dimensional quantitative structure-activity relationship modeling of binding affinity and functional potency

    DEFF Research Database (Denmark)

    Tosco, Paolo; Ahring, Philip K; Dyhring, Tino

    2009-01-01

    Complementary 3D-QSAR modeling of binding affinity and functional potency is proposed as a tool to pinpoint the molecular features of the ligands, and the corresponding amino acids in the receptor, responsible for high affinity binding vs those driving agonist behavior and receptor activation. Th...

  17. Opportunities and strategies to further reduce animal use for Leptospira vaccine potency testing.

    Science.gov (United States)

    Walker, A; Srinivas, G B

    2013-09-01

    Hamsters are routinely infected with virulent Leptospira for two purposes in the regulation of biologics: the performance of Codified potency tests and maintenance of challenge culture for the Codified potency tests. Options for reducing animal use in these processes were explored in a plenary lecture at the "International Workshop on Alternative Methods for Leptospira Vaccine Potency Testing: State of the Science and the Way Forward" held at the Center for Veterinary Biologics in September 2012. The use of validated in vitro potency assays such as those developed by the U.S. Department of Agriculture for Leptospira (L.) canicola, Leptospira grippotyphosa, Leptospira pomona, and Leptospira icterohaemorrhagiae rather than the Codified hamster vaccination-challenge assay was encouraged. Alternatives such as reduced animal numbers in the hamster vaccination-challenge testing were considered for problematic situations. Specifically, the merits of sharing challenge controls, reducing group sizes, and eliminating animals for concurrent challenge dose titration were assessed. Options for maintaining virulent, stable cultures without serial passage through hamsters or with decreased hamster use were also discussed. The maintenance of virulent Leptospira without the use of live animals is especially difficult since a reliable means to maintain virulence after multiple in vitro passages has not yet been identified. Published by Elsevier Ltd.

  18. Embryotoxic and pharmacologic potency ranking of six azoles in the rat whole embryo culture by morphological and transcriptomic analysis

    International Nuclear Information System (INIS)

    Dimopoulou, Myrto; Verhoef, Aart; Pennings, Jeroen L.A.; Ravenzwaay, Bennard van; Rietjens, Ivonne M.C.M.; Piersma, Aldert H.

    2017-01-01

    Differential gene expression analysis in the rat whole embryo culture (WEC) assay provides mechanistic insight into the embryotoxicity of test compounds. In our study, we hypothesized that comparative analysis of the transcriptomes of rat embryos exposed to six azoles (flusilazole, triadimefon, ketoconazole, miconazole, difenoconazole and prothioconazole) could lead to a better mechanism-based understanding of their embryotoxicity and pharmacological action. For evaluating embryotoxicity, we applied the total morphological scoring system (TMS) in embryos exposed for 48 h. The compounds tested showed embryotoxicity in a dose-response fashion. Functional analysis of differential gene expression after 4 h exposure at the ID 10 (effective dose for 10% decreased TMS), revealed the sterol biosynthesis pathway and embryonic development genes, dominated by genes in the retinoic acid (RA) pathway, albeit in a differential way. Flusilazole, ketoconazole and triadimefon were the most potent compounds affecting the RA pathway, while in terms of regulation of sterol function, difenoconazole and ketoconazole showed the most pronounced effects. Dose-dependent analysis of the effects of flusilazole revealed that the RA pathway related genes were already differentially expressed at low dose levels while the sterol pathway showed strong regulation at higher embryotoxic doses, suggesting that this pathway is less predictive for the observed embryotoxicity. A similar analysis at the 24-hour time point indicated an additional time-dependent difference in the aforementioned pathways regulated by flusilazole. In summary, the rat WEC assay in combination with transcriptomics could add a mechanistic insight into the embryotoxic potency ranking and pharmacological mode of action of the tested compounds. - Highlights: • Embryonic exposure to azoles revealed concentration-dependent malformations. • Transcriptomics could enhance the mechanistic knowledge of embryotoxicants. • Retinoic

  19. Embryotoxic and pharmacologic potency ranking of six azoles in the rat whole embryo culture by morphological and transcriptomic analysis

    Energy Technology Data Exchange (ETDEWEB)

    Dimopoulou, Myrto, E-mail: myrto.dimopoulou@wur.nl [Division of Toxicology, Wageningen University (Netherlands); National Institute of Public Health and the Environment (RIVM), Bilthoven (Netherlands); Verhoef, Aart; Pennings, Jeroen L.A. [National Institute of Public Health and the Environment (RIVM), Bilthoven (Netherlands); Ravenzwaay, Bennard van [Division of Toxicology, Wageningen University (Netherlands); BASF SE, Experimental Toxicology and Ecology, Ludwigshafen (Germany); Rietjens, Ivonne M.C.M. [Division of Toxicology, Wageningen University (Netherlands); Piersma, Aldert H. [National Institute of Public Health and the Environment (RIVM), Bilthoven (Netherlands); Institute for Risk Assessment Sciences, Utrecht University, Utrecht (Netherlands)

    2017-05-01

    Differential gene expression analysis in the rat whole embryo culture (WEC) assay provides mechanistic insight into the embryotoxicity of test compounds. In our study, we hypothesized that comparative analysis of the transcriptomes of rat embryos exposed to six azoles (flusilazole, triadimefon, ketoconazole, miconazole, difenoconazole and prothioconazole) could lead to a better mechanism-based understanding of their embryotoxicity and pharmacological action. For evaluating embryotoxicity, we applied the total morphological scoring system (TMS) in embryos exposed for 48 h. The compounds tested showed embryotoxicity in a dose-response fashion. Functional analysis of differential gene expression after 4 h exposure at the ID{sub 10} (effective dose for 10% decreased TMS), revealed the sterol biosynthesis pathway and embryonic development genes, dominated by genes in the retinoic acid (RA) pathway, albeit in a differential way. Flusilazole, ketoconazole and triadimefon were the most potent compounds affecting the RA pathway, while in terms of regulation of sterol function, difenoconazole and ketoconazole showed the most pronounced effects. Dose-dependent analysis of the effects of flusilazole revealed that the RA pathway related genes were already differentially expressed at low dose levels while the sterol pathway showed strong regulation at higher embryotoxic doses, suggesting that this pathway is less predictive for the observed embryotoxicity. A similar analysis at the 24-hour time point indicated an additional time-dependent difference in the aforementioned pathways regulated by flusilazole. In summary, the rat WEC assay in combination with transcriptomics could add a mechanistic insight into the embryotoxic potency ranking and pharmacological mode of action of the tested compounds. - Highlights: • Embryonic exposure to azoles revealed concentration-dependent malformations. • Transcriptomics could enhance the mechanistic knowledge of embryotoxicants.

  20. The potency of monoethanolamine in biogas purification and upgrading

    Directory of Open Access Journals (Sweden)

    O.I. Maile

    2017-12-01

    Full Text Available Biogas has been exploited as one of the alternative sources of renewable energy having the potential to replace fossil fuels. It contains impurities when raw, as it consists of 50–70% methane (CH4, 30–50% carbon dioxide (CO2 and trace gases such as hydrogen sulfide (H2S. Chemical absorption is often a preferred purification technique in industrial applications because it has high efficiencies, removes H2S completely, operates at low pressures, and has higher reaction rates. The focus of this study is on amines as they are widely used worldwide to purify biogas. A continuous system was used where 1 L digester was used for biogas production which was bubbled through an absorbent in 500 mL gas washing bottle. The gas exiting the absorption column was analyzed using Gas Chromatography. The methane yield obtained in this study was higher because MEA is a good absorbent. The biomethane potential was found to be 0.40 m3 CH4/kg VS (volatile solids. An increase in concentration resulted in increased co2 absorption capacity and rate, an average of 76%, 78%, and 84% vol from an initial concentration of 52% vol were achieved for the respective concentrations. The CH4 content of the purified biogas improved with increasing temperature. The removal efficiency of carbon dioxide increased from 66% at room temperature to 77% at 40 °C. Temperature of the solvent increased the absorption capacity and carbon dioxide removal efficiency of the process. Keywords: Absorption rate, Concentration, Removal efficiency, Solvent, Temperature

  1. Peptide and small molecules rescue the functional activity and agonist potency of dysfunctional human melanocortin-4 receptor polymorphisms.

    Science.gov (United States)

    Xiang, Zhimin; Pogozheva, Irina D; Sorenson, Nicholas B; Wilczynski, Andrzej M; Holder, Jerry Ryan; Litherland, Sally A; Millard, William J; Mosberg, Henry I; Haskell-Luevano, Carrie

    2007-07-17

    The melanocortin pathway, specifically the melanocortin-4 receptor and the cognate endogenous agonist and antagonist ligands, have been strongly implicated in the regulation of energy homeostasis and satiety. Genetic studies of morbidly obese human patients and normal weight control patients have resulted in the discovery of over 70 human melanocortin-4 receptor (MC4R) polymorphisms observed as both heterozygous and homozygous forms. A number of laboratories have been studying these hMC4R polymorphisms attempting to understand the molecular mechanism(s) that might explain the obese human phenotype. Herein, we have studied 13 polymorphic hMC4Rs that have been identified to possess statistically significant decreased endogenous agonist potency with synthetic peptides and small molecules attempting to identify ligands that can pharmacologically rescue the hMC4R polymorphic agonist response. The ligands examined in this study include NDP-MSH, MTII, Ac-His-DPhe-Arg-Trp-NH2 (JRH887-9), Ac-Anc-DPhe-Arg-Trp-NH2 (amino-2-naphtylcarboxylic acid, Anc, JRH420-12), Ac-His-(pI)DPhe-Arg-Trp-NH2 (JRH322-18), chimeric AGRP-melanocortin based ligands (Tyr-c[Cys-His-DPhe-Arg-Trp-Asn-Ala-Phe-Cys]-Tyr-NH2, AMW3-130 and Ac-mini-(His-DPhe-Arg-Trp)-hAGRP-NH2, AMW3-106), and the small molecules JB25 and THIQ. The hMC4R polymorphisms included in this study are S58C, N97D, I102S, L106P, S127L, T150I, R165Q, R165W, L250Q, G252S, C271Y, Y287Stop, and I301T. These studies resulted in the NDP-MSH, MTII, AMW3-130, THIQ, and AMW3-106 ligands possessing nanomolar to subnanomolar agonist potency at the hMC4R polymorphisms examined in this study. Thus, these ligands could generically rescue the potency and stimulatory response of the abnormally functioning hMC4Rs studied and may provide tools to further clarify the molecular mechanism(s) involving these receptor modifications.

  2. Validation of self-reported cannabis dose and potency: an ecological study.

    Science.gov (United States)

    van der Pol, Peggy; Liebregts, Nienke; de Graaf, Ron; Korf, Dirk J; van den Brink, Wim; van Laar, Margriet

    2013-10-01

    To assess the reliability and validity of self-reported cannabis dose and potency measures. Cross-sectional study comparing self-reports with objective measures of amount of cannabis and delta-9-tetrahydrocannabinol (THC) concentration. Ecological study with assessments at participants' homes or in a coffee shop. Young adult frequent cannabis users (n = 106) from the Dutch Cannabis Dependence (CanDep) study. The objectively measured amount of cannabis per joint (dose in grams) was compared with self-reported estimates using a prompt card and average number of joints made from 1 g of cannabis. In addition, objectively assessed THC concentration in the participant's cannabis was compared with self-reported level of intoxication, subjective estimate of cannabis potency and price per gram of cannabis. Objective estimates of doses per joint (0.07-0.88 g/joint) and cannabis potency (1.1-24.7%) varied widely. Self-reported measures of dose were imprecise, but at group level, average dose per joint was estimated accurately with the number of joints made from 1 g [limit of agreement (LOA) = -0.02 g, 95% confidence interval (CI) = -0.29; 0.26], whereas the prompt card resulted in serious underestimation (LOA = 0.14 g, 95% CI = -0.10; 0.37). THC concentration in cannabis was associated with subjective potency ['average' 3.77% (P = 0.002) and '(very) strong' 5.13% more THC (P cannabis] and with cannabis price (about 1% increase in THC concentration per euro spent on 1 g of cannabis, P cannabis use appear at best to be associated weakly with objective measures. Of the self-report measures, number of joints per gram, cannabis price and subjective potency have at least some validity. © 2013 Society for the Study of Addiction.

  3. Development of a surrogate angiogenic potency assay for clinical-grade stem cell production.

    Science.gov (United States)

    Lehman, Nicholas; Cutrone, Rochelle; Raber, Amy; Perry, Robert; Van't Hof, Wouter; Deans, Robert; Ting, Anthony E; Woda, Juliana

    2012-09-01

    Clinical results from acute myocardial infarction (AMI) patients treated with MultiStem®, a large-scale expanded adherent multipotent progenitor cell population (MAPC), have demonstrated a strong safety and benefit profile for these cells. The mechanism of benefit with MAPC treatment is a result, in part, of its ability to induce neovascularization through trophic support. Production of clinical-grade stem cell products requires the development of lot-release criteria based on potency assays that directly reflect the fundamental mechanistic pathway underlying the therapeutic response to verify manufacturing process consistency and product potency. Using an in vitro endothelial tube formation assay, a potency assay has been developed that reflects MAPC pro-angiogenic activity. Serum-free conditioned media collected from MAPC culture induced endothelial tube formation. A proteomic survey of angiogenic factors produced by the cells in vitro revealed candidate factors linked to angiogenic potency. Three cytokines, chemokine (C-X-C motif) ligand 5 (CXCL5), interleukin 8 (IL-8) and vascular endothelial growth factor (VEGF), were required for this angiogenic activity. Depletion of any of these factors from the media prevented tube formation, while adding back increasing amounts of these cytokines into the depleted serum-free conditioned media established the lower limits of each of the cytokines required to induce angiogenesis. A necessary threshold of angiogenic factor expression was established using an in vitro angiogenesis assay. By correlating the levels of the cytokines required to induce tube formation in vitro with levels of the factors found in the spent media from manufacturing production runs, detection of these factors was identified as a surrogate potency assay with defined pass/fail criteria.

  4. Potency of carbapenems for the prevention of carbapenem-resistant mutants of Pseudomonas aeruginosa: the high potency of a new carbapenem doripenem.

    Science.gov (United States)

    Sakyo, Shihomi; Tomita, Haruyoshi; Tanimoto, Koichi; Fujimoto, Shuhei; Ike, Yasuyoshi

    2006-04-01

    The potencies of the carbapenems; doripenem (DRPM), meropenem (MEPM) and imipenem (IPM) in preventing the emergence of carbapenem-resistant mutants were examined in Pseudomonas aeruginosa strains. The carbapenems predominantly selected carbapenem-resistant mutants or carbapenem mutants with reduced susceptibilities that were specifically resistant to carbapenems and had arisen as a result of the reduced level of expression of the outer membrane protein with a molecular weight of about 48,000 (OprD). The potency of carbapenems in preventing the growth of the mutants differed for DRPM, MEPM and IPM. The isolation frequency of the mutant was examined on agar plates containing each of the carbapenems at a concentration of 1/2 or 1/4 MIC of each carbapenem for that mutant. Mutants were not selected on agar containing DRPM at a frequency of greater than 10(-9) per cell per generation, whereas mutants of each strain were selected on agar containing MEPM or IPM at frequencies of 10(-7) to 10(-9) per cell per generation. The drug concentrations and the drug concentration range for the selective increase of carbapenem resistant mutants in the broth culture containing each carbapenem differed for each carbapenem. DRPM exhibited both the lowest drug concentration and the narrowest range of drug concentration for selection of the carbapenem-resistant mutants. The results shown in this report indicated that DRPM exhibited the greatest ability to prevent the emergence of the mutant.

  5. Considerations for potency equivalent calculations in the Ah receptor-based CALUX bioassay: normalization of superinduction results for improved sample potency estimation.

    Science.gov (United States)

    Baston, David S; Denison, Michael S

    2011-02-15

    The chemically activated luciferase expression (CALUX) system is a mechanistically based recombinant luciferase reporter gene cell bioassay used in combination with chemical extraction and clean-up methods for the detection and relative quantitation of 2,3,7,8-tetrachlorodibenzo-p-dioxin and related dioxin-like halogenated aromatic hydrocarbons in a wide variety of sample matrices. While sample extracts containing complex mixtures of chemicals can produce a variety of distinct concentration-dependent luciferase induction responses in CALUX cells, these effects are produced through a common mechanism of action (i.e. the Ah receptor (AhR)) allowing normalization of results and sample potency determination. Here we describe the diversity in CALUX response to PCDD/Fs from sediment and soil extracts and not only report the occurrence of superinduction of the CALUX bioassay, but we describe a mechanistically based approach for normalization of superinduction data that results in a more accurate estimation of the relative potency of such sample extracts. Copyright © 2010 Elsevier B.V. All rights reserved.

  6. Assessment of metal sensitizer potency with the reconstructed human epidermis IL-18 assay.

    Science.gov (United States)

    Gibbs, Susan; Kosten, Ilona; Veldhuizen, Rosalien; Spiekstra, Sander; Corsini, Emanuela; Roggen, Erwin; Rustemeyer, Thomas; Feilzer, Albert J; Kleverlaan, Cees J

    2018-01-15

    According to the new EU Medical Devices (MDR) legislation coming into effect in 2017, manufactures will have to comply with higher standards of quality and safety for medical devices in order to meet common safety concerns regarding such products. Metal alloys are extensively used in dentistry and medicine (e.g. orthopedic surgery and cardiology) even though clinical experience suggests that many metals are sensitizers. The aim of this study was to further test the applicability domain of the in vitro reconstructed human epidermis (RhE) IL-18 assay developed to identify contact allergens and in doing so: i) determine whether different metal salts, representing leachables from metal alloys used in medical devices, could be correctly labelled and classified; and ii) assess the ability of different salts for the same metal to penetrate the skin stratum corneum. Twenty eight chemicals including 15 metal salts were topically exposed to RhE. Nickel, chrome, gold, palladium were each tested in two different salt forms, and titanium in 4 different salt forms. Metal salts were labelled (YES/NO) as sensitizer if a threshold of more than 5 fold IL18 release was reached. The in vitro estimation of expected sensitization induction level (potency) was assessed by interpolating in vitro EC50 and IL-18 SI2 with LLNA EC3 and human NOEL values from standard reference curves generated using DNCB (extreme) and benzocaine (weak). Metal salts, in contrast to other chemical sensitizers and with the exception of potassium dichromate (VI) and cobalt (II) chloride, were not identified as contact allergens since they only induced a small or no increase in IL-18 production. This finding was not related to a lack of stratum corneum skin penetration since EC50 values (decrease in metabolic activity; MTT assay) were obtained after topical RhE exposure to 8 of the 15 metal salts. For nickel, gold and palladium salts, differences in EC50 values between two salts for the same metal could not be

  7. Toots, tastes and tester shots: user accounts of drug sampling methods for gauging heroin potency.

    Science.gov (United States)

    Mars, Sarah G; Ondocsin, Jeff; Ciccarone, Daniel

    2018-05-16

    Internationally, overdose is the primary cause of death among people injecting drugs. However, since 2001, heroin-related overdose deaths in the United States (US) have risen sixfold, paralleled by a rise in the death rate attributed to synthetic opioids, particularly the fentanyls. This paper considers the adaptations some US heroin injectors are making to protect themselves from these risks. Between 2015 and 2016, a team of ethnographers collected data through semi-structured interviews and observation captured in field notes and video recording of heroin preparation/consumption. Ninety-one current heroin injectors were interviewed (Baltimore, n = 22; Chicago, n = 24; Massachusetts and New Hampshire, n = 36; San Francisco, n = 9). Experience injecting heroin ranged from methods of sampling "heroin" were identified, sometimes used in combination, ranging from non-injecting routes (snorting, smoking or tasting a small amount prior to injection) to injecting a partial dose and waiting. Partial injection took different forms: a "slow shot" where the user injected a portion of the solution in the syringe, keeping the needle in the injection site, and continuing or withdrawing the syringe or a "tester shot" where the solution was divided into separate injections. Other techniques included getting feedback from others using heroin of the same batch or observing those with higher tolerance injecting heroin from the same batch before judging how much to inject themselves. Although a minority of those interviewed described using these drug sampling techniques, there is clearly receptivity among some users to protecting themselves by using a variety of methods. The use of drug sampling as a means of preventing an overdose from injection drug use reduces the quantity absorbed at any one time allowing users to monitor drug strength and titrate their dose accordingly. Given the highly unpredictable potency of the drugs currently being sold as heroin in the US

  8. ECETOC Florence workshop on risk assessment of endocrine substances, including the potency concept.

    Science.gov (United States)

    Fegert, Ivana

    2013-12-16

    The European regulation on plant protection products (1107/2009) and the Biocidal Products Regulation (EC Regulation 528/2012) only support the marketing and use of chemicals if they do not cause endocrine disruption in humans or wildlife species. Also, substances with endocrine properties are subject to authorization under the European regulation on the registration, evaluation, authorization and restriction of chemicals (REACH; 1907/2006). Therefore, the regulatory consequences of identifying a substance as an endocrine disrupting chemical are severe. In contrast to that, basic scientific criteria, necessary to define endocrine disrupting properties, are not described in any of these legislative documents. Thus, the European Center for Ecotoxicology and Toxicology of Chemicals (ECETOC) established a task force to provide scientific criteria for the identification and assessment of chemicals with endocrine disrupting properties that may be used within the context of these three legislative texts (ECETOC, 2009a). In 2009, ECETOC introduced a scientific framework as a possible concept for identifying endocrine disrupting properties within a regulatory context (ECETOC, 2009b; Bars et al., 2011a,b). The proposed scientific criteria integrated, in a weight of evidence approach, information from regulatory (eco)toxicity studies and mechanistic/screening studies by combining evidence for adverse effects detected in apical whole-organism studies with an understanding of the mode of action (MoA) of endocrine toxicity. However, since not all chemicals with endocrine disrupting properties are of equal hazard, an adequate concept should also be able to differentiate between chemicals with endocrine properties of low concern from those of higher concern (for regulatory purposes). For this purpose, the task force refined this part of their concept. Following an investigation of the key factors at a second workshop of invited regulatory, academic and industry scientists, the

  9. [Effect of 2-phenoxyethanol on potency of Sabin inactivated poliomyelitis vaccine and its safety].

    Science.gov (United States)

    Bian, Chuan-xiu; Jiang, Shu-de; Yang, Jian-yong; Sun, Ming-bo; Xie, Ming-xue; Zhang, Xin-wen; Liao, Guo-yang; Li, Wei-dong

    2007-03-01

    To investigate the effect of 2-phenoxyethanol on potency of Sabin inactivated poliomyelitis vaccine (IPV). Sabin IPV samples containing 5 mg or 7 mg 2-phenoxyethanol each dosage respectively were placed separately at 4 degrees C, 37 degrees C for 2 days and 7 days. D-antigen contents were tested with ELISA method. Then neutralizing antibodies in mice and guinea pigs were detected. The safety experiment was performed according to unusual toxicity test of China requirement for biological product. After addition of 2-phenoxyethanol, the I, II, and III D-antigen contents of Sabin IPV did not change. The antibody levels in mice and guinea pigs were not different between experimental group and control group. Animals were safe during observation period. 2-Phenoxyethanol had no effect on potency and safety of Sabin IPV. It can be used as antiseptic for Sabin IPV.

  10. Potency of Education Historical Tourismof World War II Japanese Cavesand Bunkersin Coastal Banyuwangi

    Science.gov (United States)

    Rahmi, Miftahul; Qiram, Ikhwanul

    2018-05-01

    Banyuwangi district has some Japanese caves and bunkers of World War II. The location of the objects are along the Banyuwangi coast as a maritime defense during the war. This structures can be used as education historical tourism object. There are many similar structures in other area that have been neglected and do not get enough preservation attention. This research is aimed to identify the potency of education historical tourism of Japanese caves and bunker in Banyuwangi. The research is done by field research for the observation of objects physical condition. It is also done by interviewing local government, historical actors and surrounding community. The result shows that the caves and bunker have a great potency but have not been used as education historical object.

  11. Potency of carcinogens derived from covalent DNA binding and stimulation of DNA synthesis in rat liver

    International Nuclear Information System (INIS)

    Lutz, W.K.; Buesser, M.T.; Sagelsdorff, P.

    1984-01-01

    In order to investigate the role of the stimulation of cell division for the initiation (and possibly promotion) of liver tumors by chemical carcinogens, the incorporation of radiolabelled thymidine into liver DNA was determined in male rats. Single doses of various levels of aflatoxin B1, benzidine and carbon tetrachloride (all known to be genotoxic via DNA binding) did not affect cell division, whereas several hepatocarcinogens known not to bind to DNA (alpha-HCH, clofibrate, and 2,3,7,8-tetrachlorodibenzo-p-dioxin) gave rise to a dose-dependent stimulation of liver DNA synthesis within 24 h. An equation combining the influences of mitotic stimulation, expressed as dose required to double the control level of DNA synthesis, and DNA binding potency, expressed as the Covalent Binding Index, correlated well with the carcinogenic potency for both classes of hepatocarcinogens

  12. Relationship between potency and boiling point of general anesthetics: a thermodynamic consideration.

    Science.gov (United States)

    Dastmalchi, S; Barzegar-Jalali, M

    2000-07-20

    The most important group of nonspecific drugs is that of the general anesthetics. These nonspecific compounds vary greatly in structure, from noble gases such as Ar or Xe to complex steroids. Since the development of clinical anesthesia over a century ago, there has been a vast amount of research and speculation concerning the mechanism of action of general anesthetics. Despite these efforts, the exact mechanism remains unknown. Many theories of narcosis do not explain how unconsciousness is produced at a molecular level, but instead relate some physicochemical property of anesthetic agents to their anesthetic potencies. In this paper, we address some of those physicochemical properties, with more emphasis on correlating the anesthetic potency of volatile anesthetics to their boiling points based on thermodynamic principles.

  13. In vivo potency of different ligands on voltage-gated sodium channels.

    Science.gov (United States)

    Safrany-Fark, Arpad; Petrovszki, Zita; Kekesi, Gabriella; Liszli, Peter; Benedek, Gyorgy; Keresztes, Csilla; Horvath, Gyongyi

    2015-09-05

    The Ranvier nodes of thick myelinated nerve fibers contain almost exclusively voltage-gated sodium channels (Navs), while the unmyelinated fibers have several receptors (e.g., cannabinoid, transient receptor potential vanilloid receptor 1), too. Therefore, a nerve which contains only motor fibers can be an appropriate in vivo model for selective influence of Navs. The goals were to evaluate the potency of local anesthetic drugs on such a nerve in vivo; furthermore, to investigate the effects of ligands with different structures (arachidonic acid, anandamide, capsaicin and nisoxetine) that were proved to inhibit Navs in vitro with antinociceptive properties. The marginal mandibular branch of the facial nerve was explored in anesthetized Wistar rats; after its stimulation, the electrical activity of the vibrissae muscles was registered following the perineural injection of different drugs. Lidocaine, bupivacaine and ropivacaine evoked dose-dependent decrease in electromyographic activity, i.e., lidocaine had lower potency than bupivacaine or ropivacaine. QX-314 did not cause any effect by itself, but its co-application with lidocaine produced a prolonged inhibition. Nisoxetine had a very low potency. While anandamide and capsaicin in high doses caused about 50% decrease in the amplitude of action potential, arachidonic acid did not influence the responses. We proved that the classical local anesthetics have high potency on motor nerves, suggesting that this method might be a reliable model for selective targeting of Navs in vivo circumstances. It is proposed that the effects of these endogenous lipids and capsaicin on sensory fibers are not primarily mediated by Navs. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. ''Spare'' alpha 1-adrenergic receptors and the potency of agonists in rat vas deferens

    International Nuclear Information System (INIS)

    Minneman, K.P.; Abel, P.W.

    1984-01-01

    The existence of ''spare'' alpha 1-adrenergic receptors in rat vas deferens was examined directly using radioligand binding assays and contractility measurements. Alpha 1-adrenergic receptors in homogenates of rat vas deferens were labeled with [ 125 I]BE 2254 ( 125 IBE). Norepinephrine and other full alpha 1-adrenergic receptor agonists were much less potent in inhibiting 125 IBE binding than in contracting the vas deferens in vitro. Treatment with 300 nM phenoxybenzamine for 10 min to irreversibly inactivate alpha 1-adrenergic receptors caused a large decrease in the potency of full agonists in causing contraction of this tissue and a 23-48% decrease in the maximal contraction observed. Using those data, equilibrium constants for activation (Kact values) of the receptors by agonists were calculated. These Kact values agreed well with the equilibrium binding constants (KD values) determined from displacement of 125 IBE binding. The reduction in alpha 1-adrenergic receptor density following phenoxybenzamine treatment was determined by Scatchard analysis of specific 125 IBE binding sites and compared with the expected reduction (q values) calculated from the agonist dose-response curves before and after phenoxybenzamine treatment. This suggests that phenoxybenzamine functionally inactivates alpha 1-adrenergic receptors at or near the receptor binding site. These experiments suggest that the potencies of agonists in activating alpha 1-adrenergic receptors in rat vas deferens agree well with their potencies in binding to the receptors. The greater potency of agonists in causing contraction may be due to spare receptors in this tissue. The data also demonstrate that phenoxybenzamine irreversibly inactivates alpha 1-adrenergic receptors in rat vas deferens, but that the decrease in receptor density is much smaller than that predicted from receptor theory

  15. Anticancer potency of black sea cucumber (Holothuria atra) from Mentawai Islands, Indonesia

    OpenAIRE

    Mieke Hemiawati Satari; Utmi Arma; Syafruddin Ilyas; Dian Handayani

    2017-01-01

    ABSTRACT Introduction: The source of bioactive compounds believed to have strong anticancer potency is derived from sea cucumber. Black sea cucumber (Holothuria atra) is a dominant species in Mentawai Islands, West Sumatera, Indonesia. Key factor compound that acts as anticancer in sea cucumber extract is tritepenoid also known as Frondoside A. The purpose of this study was to determine the effectiveness of the active compound taken from black sea cucumber as anticancer. Methods: Methods u...

  16. Generation of Arctic-like Rabies Viruses Containing Chimeric Glycoproteins Enables Serological Potency Studies.

    OpenAIRE

    Bentley, Emma; Ali, Ruqiyo; Horton, Daniel; Corti, Davide; Banyard, Ashley; Fooks, Anthony; Wright, Edward

    2017-01-01

    Rabies viruses have the highest case fatality rate of any known virus and are responsible for an estimated 60,000 deaths each year. This is despite the fact that there are highly efficacious vaccines and post-exposure prophylaxis available. However, while it is assumed these biologics provide protection against all rabies virus isolates, there are certain subdivisions of RABV lineages, such as within the Arctic-like RABV (AL rabies virus lineage, where data is limited and thus the potency of ...

  17. Chemical composition and antimicrobial potency of essential oils from roots of Pinus growing in Algeria

    OpenAIRE

    Nadia FEKIH; Hocine ALLALI; Abdeslem Nacer AREZKI AIT; Salima MERGHACHE; Djamila MAGHNIA; Jean COSTA

    2016-01-01

    The objective of this study is to determine the chemical composition and antimicrobial potency of essential oils of three roots of genus Pinus (P. halepensis, P. pinea and P. pinaster) growing in Algeria for the first time. The essential oils used in the present study were isolated by hydrodistillation using a Cleavenger-type apparatus according the European Pharmacopoeia, and identified by GC and GC-MS. 14, 12, 11 constituents were identified, representing an average of 98.8 %, 9...

  18. Progress in applying the Three Rs to the potency testing of Botulinum toxin type A.

    Science.gov (United States)

    Straughan, Donald

    2006-06-01

    Botulinum toxin type A (BTA) is being increasingly used for a range of therapeutic purposes and also for cosmetic reasons. For many years, the potency of BTA has been measured by using an LD50 assay in mice. This assay is a cause for concern due to its unpleasant nature and extreme severity, and the requirement for high numbers of mice to be used. Alternatives to this potency assay are presently reviewed with particular reference to the work at the National Institute for Biological Standards and Control (NIBSC), and to recent work by the UK manufacturer of the substance. An in vivo local paralysis assay with considerably less severity has been developed and is in use at the NIBSC. Alternative, ex vivo functional assays in use include the measurement of BTA-induced paralysis of neurally-stimulated rodent diaphragm or rat intercostal muscle. The latter method has the advantage of allowing more preparations to be derived from one animal. However, these ex vivo methods have not yet been fully validated and accepted by regulatory agencies as potency assays. Endopeptidase assays, although not measuring muscle paralysis directly, may provide a very useful consistency test for batch release and may replace the routine use of the LD50 test for that purpose. These assays measure the cleavage of the SNAP-25 protein (the final stage of BTA action), and have been validated for batch release by the National Control Laboratory (NIBSC), and are in regular use there. ELISA assays, used alongside the endopeptidase assay, also provide useful confirmatory information on the amounts of functional (and non-functional) BTA present. The UK manufacturer is further validating its endopeptidase assay, an ex vivo muscle assay and an ELISA. It is anticipated that their work will lead to a change in the product license, hopefully within the next two years, and will form a critical milestone towards the end of the LD50 potency test.

  19. Novel Anticonvulsant Analogs of Dextromethorphan: Improved Efficacy, Potency, Duration and Side-Effect Profile

    Science.gov (United States)

    1994-02-01

    dextromethorphan (014, [+J-3-aethyl-l7-methylmorphinan) may be, in part, due to its ____________________metabolism to the PCP-like compound... Dextromethorphan : Improved Efficacy, Potency, Duration and Side-Effect Profile1 FRANK C. TORTELLA, LYDIA ROBLES, JEFFREY M. WITKIN and AMY HAUCK NEWMAN... dextromethorphan ; NMDA, N-methyl-D-aspartate; PCP, phencyclidine hydrochloride; DX, dextrorphan; AHN649, [(+)-3- amino-1 7-methylmorphinan]; AHN1 -036

  20. Development and Rainfed Paddy Soils Potency Derived From Lacustrine Material in Paguyaman, Gorontalo

    OpenAIRE

    Nurdin

    2011-01-01

    Rainfed paddy soils that are derived from lacustrine and include of E4 agroclimatic zone have many unique properties and potentially for paddy and corn plantations. This sreseach was aimed to: (1) study the soil development of rainfed paddy soils derived from lacustrine and (2) evaluate rainfed paddy soils potency for paddy and corn in Paguyaman. Soil samples were taken from three profiles according to toposequent, and they were analyzed in laboratory. Data were analyzed with descripti...

  1. Parametric Effect of Sodium Hydroxide and Sodium Carbonate on the Potency of a Degreaser

    OpenAIRE

    Babatope Abimbola Olufemi

    2016-01-01

    Experimental and statistical analysis was carried out on the comparative effect of sodium hydroxide and sodium carbonate on the potency of a laboratory produced degreaser in this work. The materials used include; octadecyl benzene sulphonic acid, sodium hydroxide, sodium carbonate, sodium metasilicate, carboxyl methyl cellulose (C.M.C), formadelhyde, perfume, colourant and distilled water. Different samples of degreaser were produced with varying composition of sodium hydroxide and sodium car...

  2. N-Aryl-oxazolidin-2-imine Muscle Selective Androgen Receptor Modulators Enhance Potency through Pharmacophore Reorientation

    Energy Technology Data Exchange (ETDEWEB)

    Nirschl, Alexandra A.; Zou, Yan; Krystek, Jr., Stanley R.; Sutton, James C.; Simpkins, Ligaya M.; Lupisella, John A.; Kuhns, Joyce E.; Seethala, Ramakrishna; Golla, Rajasree; Sleph, Paul G.; Beehler, Blake C.; Grover, Gary J.; Egan, Donald; Fura, Aberra; Vyas, Viral P.; Li, Yi-Xin; Sack, John S.; Kish, Kevin F.; An, Yongmi; Bryson, James A.; Gougoutas, Jack Z.; DiMarco, John; Zahler, Robert; Ostrowski, Jacek; Hamann, Lawrence G.; (BMS)

    2010-11-09

    A novel selective androgen receptor modulator (SARM) scaffold was discovered as a byproduct obtained during synthesis of our earlier series of imidazolidin-2-ones. The resulting oxazolidin-2-imines are among the most potent SARMs known, with many analogues exhibiting sub-nM in vitro potency in binding and functional assays. Despite the potential for hydrolytic instability at gut pH, compounds of the present class showed good oral bioavailability and were highly active in a standard rodent pharmacological model.

  3. Critical elements in the development of cell therapy potency assays for ischemic conditions.

    Science.gov (United States)

    Porat, Yael; Abraham, Eytan; Karnieli, Ohad; Nahum, Sagi; Woda, Juliana; Zylberberg, Claudia

    2015-07-01

    A successful potency assay for a cell therapy product (CTP) used in the treatment of ischemic conditions should quantitatively measure relevant biological properties that predict therapeutic activity. This is especially challenging because of numerous degrees of complexity stemming from factors that include a multifactorial complex mechanism of action, cell source, inherent cell characteristics, culture method, administration mode and the in vivo conditions to which the cells are exposed. The expected biological function of a CTP encompasses complex interactions that range from a biochemical, metabolic or immunological activity to structural replacement of damaged tissue or organ. Therefore, the requirements for full characterization of the active substance with respect to biological function could be taxing. Moreover, the specific mechanism of action is often difficult to pinpoint to a specific molecular entity; rather, it is more dependent on the functionality of the cellular components acting in a in a multifactorial fashion. In the case of ischemic conditions, the cell therapy mechanism of action can vary from angiogenesis, vasculogenesis and arteriogenesis that may activate different pathways and clinical outcomes. The CTP cellular attributes with relation to the suggested mechanism of action can be used for the development of quantitative and reproducible analytical potency assays. CTPs selected and released on the basis of such potency assays should have the highest probability of providing meaningful clinical benefit for patients. This White Paper will discuss and give examples for key elements in the development of a potency assay for treatment of ischemic disorders treated by the use of CTPs. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  4. Potency testing of veterinary vaccines: the way from in vivo to in vitro.

    Science.gov (United States)

    Romberg, Judith; Lang, Stefan; Balks, Elisabeth; Kamphuis, Elisabeth; Duchow, Karin; Loos, Daniela; Rau, Henriette; Motitschke, Andreas; Jungbäck, Carmen

    2012-01-01

    Current quality control of inactivated animal vaccines still focuses on the potency of final products in a batch-wise manner. Animal welfare concerns as well as scientific considerations have led to the '3Rs-concept' that comprises the refinement of animal procedures, the reduction of animal numbers, and the replacement of animal models. Although the 3Rs-concept has been widely accepted as a fundamental principle, the number of approved alternatives for in vivo tests is still limited. To promote further progress, the international scientific workshop 'Potency Testing of Veterinary Vaccines: The Way from in vivo to in vitro' was held at the Paul-Ehrlich-Institut in Langen, Germany, on 01-03 December 2010. More than 130 participants from industry, academia and regulatory authorities discussed the current state of the 3Rs-concept, examples of its successful implementation as well as still existing hurdles. Special emphasis was laid on the 'consistency approach' that aims to ensure relevant quality attributes of vaccine batches by in vitro analyses during production rather than by in vivo potency tests on the final product. This report provides an overview of the insights gained, including the recommendations produced at the end of the workshop. Copyright © 2011. Published by Elsevier Ltd.. All rights reserved.

  5. Traditional marijuana, high-potency cannabis and synthetic cannabinoids: increasing risk for psychosis.

    Science.gov (United States)

    Murray, Robin M; Quigley, Harriet; Quattrone, Diego; Englund, Amir; Di Forti, Marta

    2016-10-01

    Epidemiological evidence demonstrates that cannabis use is associated with an increased risk of psychotic outcomes, and confirms a dose-response relationship between the level of use and the risk of later psychosis. High-potency cannabis and synthetic cannabinoids carry the greatest risk. Experimental administration of tetrahydrocannabinol, the active ingredient of cannabis, induces transient psychosis in normal subjects, but this effect can be ameliorated by co-administration of cannabidiol. This latter is a constituent of traditional hashish, but is largely absent from modern high-potency forms of cannabis. Argument continues over the extent to which genetic predisposition is correlated to, or interacts with, cannabis use, and what proportion of psychosis could be prevented by minimizing heavy use. As yet, there is not convincing evidence that cannabis use increases risk of other psychiatric disorders, but there are no such doubts concerning its detrimental effect on cognitive function. All of the negative aspects are magnified if use starts in early adolescence. Irrespective of whether use of cannabis is decriminalized or legalized, the evidence that it is a component cause of psychosis is now sufficient for public health messages outlining the risk, especially of regular use of high-potency cannabis and synthetic cannabinoids. © 2016 World Psychiatric Association.

  6. Traditional marijuana, high‐potency cannabis and synthetic cannabinoids: increasing risk for psychosis

    Science.gov (United States)

    Murray, Robin M.; Quigley, Harriet; Quattrone, Diego; Englund, Amir; Di Forti, Marta

    2016-01-01

    Epidemiological evidence demonstrates that cannabis use is associated with an increased risk of psychotic outcomes, and confirms a dose‐response relationship between the level of use and the risk of later psychosis. High‐potency cannabis and synthetic cannabinoids carry the greatest risk. Experimental administration of tetrahydrocannabinol, the active ingredient of cannabis, induces transient psychosis in normal subjects, but this effect can be ameliorated by co‐administration of cannabidiol. This latter is a constituent of traditional hashish, but is largely absent from modern high‐potency forms of cannabis. Argument continues over the extent to which genetic predisposition is correlated to, or interacts with, cannabis use, and what proportion of psychosis could be prevented by minimizing heavy use. As yet, there is not convincing evidence that cannabis use increases risk of other psychiatric disorders, but there are no such doubts concerning its detrimental effect on cognitive function. All of the negative aspects are magnified if use starts in early adolescence. Irrespective of whether use of cannabis is decriminalized or legalized, the evidence that it is a component cause of psychosis is now sufficient for public health messages outlining the risk, especially of regular use of high‐potency cannabis and synthetic cannabinoids. PMID:27717258

  7. Stereoselective potencies and relative toxicities of γ-coniceine and N-methylconiine enantiomers.

    Science.gov (United States)

    Lee, Stephen T; Green, Benedict T; Welch, Kevin D; Jordan, Glenn T; Zhang, Qian; Panter, Kip E; Hughes, David; Chang, Cheng-Wei Tom; Pfister, James A; Gardner, Dale R

    2013-04-15

    γ-Coniceine, coniine, and N-methylconiine are toxic alkaloids present in poison hemlock (Conium maculatum). We previously reported the comparison of the relative potencies of (+)- and (-)-coniine enantiomers. In this study, we synthesized γ-coniceine and the enantiomers of N-methylconiine and determined the biological activity of γ-coniceine and each of the N-methylconiine enantiomers in vitro and in vivo. The relative potencies of these piperidine alkaloids on cells expressing human fetal muscle-type nicotinic acetylcholine receptors had the rank order of γ-coniceine > (-)-N-methylconiine > (±)-N-methylconiine > (+)-N-methylconiine. The relative lethalities of γ-coniceine and (-)-, (±)-, and (+)-N-methylconiine in vivo using a mouse bioassay were 4.4, 16.1, 17.8, and 19.2 mg/kg, respectively. The results from this study suggest γ-coniceine is a more potent agonist than the enantiomers of N-methylconiine and that there is a stereoselective difference in the in vitro potencies of the enantiomers of N-methylconiine that correlates with the relative toxicities of the enantiomers in vivo.

  8. Potency values from the local lymph node assay: application to classification, labelling and risk assessment.

    Science.gov (United States)

    Loveless, S E; Api, A-M; Crevel, R W R; Debruyne, E; Gamer, A; Jowsey, I R; Kern, P; Kimber, I; Lea, L; Lloyd, P; Mehmood, Z; Steiling, W; Veenstra, G; Woolhiser, M; Hennes, C

    2010-02-01

    Hundreds of chemicals are contact allergens but there remains a need to identify and characterise accurately skin sensitising hazards. The purpose of this review was fourfold. First, when using the local lymph node assay (LLNA), consider whether an exposure concentration (EC3 value) lower than 100% can be defined and used as a threshold criterion for classification and labelling. Second, is there any reason to revise the recommendation of a previous ECETOC Task Force regarding specific EC3 values used for sub-categorisation of substances based upon potency? Third, what recommendations can be made regarding classification and labelling of preparations under GHS? Finally, consider how to integrate LLNA data into risk assessment and provide a rationale for using concentration responses and corresponding no-effect concentrations. Although skin sensitising chemicals having high EC3 values may represent only relatively low risks to humans, it is not possible currently to define an EC3 value below 100% that would serve as an appropriate threshold for classification and labelling. The conclusion drawn from reviewing the use of distinct categories for characterising contact allergens was that the most appropriate, science-based classification of contact allergens according to potency is one in which four sub-categories are identified: 'extreme', 'strong', 'moderate' and 'weak'. Since draining lymph node cell proliferation is related causally and quantitatively to potency, LLNA EC3 values are recommended for determination of a no expected sensitisation induction level that represents the first step in quantitative risk assessment. 2009 Elsevier Inc. All rights reserved.

  9. Titration calorimetry of anesthetic-protein interaction: negative enthalpy of binding and anesthetic potency.

    Science.gov (United States)

    Ueda, I; Yamanaka, M

    1997-04-01

    Anesthetic potency increases at lower temperatures. In contrast, the transfer enthalpy of volatile anesthetics from water to macromolecules is usually positive. The transfer decreases at lower temperature. It was proposed that a few selective proteins bind volatile anesthetics with negative delta H, and these proteins are involved in signal transduction. There has been no report on direct estimation of binding delta H of anesthetics to proteins. This study used isothermal titration calorimetry to analyze chloroform binding to bovine serum albumin. The calorimetrically measured delta H cal was -10.37 kJ.mol-1. Thus the negative delta H of anesthetic binding is not limited to signal transduction proteins. The binding was saturable following Fermi-Dirac statistics and is characterized by the Langmuir adsorption isotherms, which is interfacial. The high-affinity association constant, K, was 2150 +/- 132 M-1 (KD = 0.47 mM) with the maximum binding number, Bmax = 3.7 +/- 0.2. The low-affinity K was 189 +/- 3.8 M-1 (KD = 5.29 mM), with a Bmax of 13.2 +/- 0.3. Anesthetic potency is a function of the activity of anesthetic molecules, not the concentration. Because the sign of delta H determines the temperature dependence of distribution of anesthetic molecules, it is irrelevant to the temperature dependence of anesthetic potency.

  10. Developmental control of transcriptional and proliferative potency during the evolutionary emergence of animals

    Science.gov (United States)

    Arenas-Mena, Cesar; Coffman, James A.

    2016-01-01

    Summary It is proposed that the evolution of complex animals required repressive genetic mechanisms for controlling the transcriptional and proliferative potency of cells. Unicellular organisms are transcriptionally potent, able to express their full genetic complement as the need arises through their life cycle, whereas differentiated cells of multicellular organisms can only express a fraction of their genomic potential. Likewise, whereas cell proliferation in unicellular organisms is primarily limited by nutrient availability, cell proliferation in multicellular organisms is developmentally regulated. Repressive genetic controls limiting the potency of cells at the end of ontogeny would have stabilized the gene expression states of differentiated cells and prevented disruptive proliferation, allowing the emergence of diverse cell types and functional shapes. We propose that distal cis-regulatory elements represent the primary innovations that set the stage for the evolution of developmental gene regulatory networks and the repressive control of key multipotency and cell-cycle control genes. The testable prediction of this model is that the genomes of extant animals, unlike those of our unicellular relatives, encode gene regulatory circuits dedicated to the developmental control of transcriptional and proliferative potency. PMID:26173445

  11. Reduction of animal suffering in rabies vaccine potency testing by introduction of humane endpoints.

    Science.gov (United States)

    Takayama-Ito, Mutsuyo; Lim, Chang-Kweng; Nakamichi, Kazuo; Kakiuchi, Satsuki; Horiya, Madoka; Posadas-Herrera, Guillermo; Kurane, Ichiro; Saijo, Masayuki

    2017-03-01

    Potency controls of inactivated rabies vaccines for human use are confirmed by the National Institutes of Health challenge test in which lethal infection with severe neurological symptoms should be observed in approximately half of the mice inoculated with the rabies virus. Weight loss, decreased body temperature, and the presence of rabies-associated neurological signs have been proposed as humane endpoints. The potential for reduction of animal suffering by introducing humane endpoints in the potency test for inactivated rabies vaccine for human use was investigated. The clinical signs were scored and body weight was monitored. The average times to death following inoculation were 10.49 and 10.99 days post-inoculation (dpi) by the potency and challenge control tests, respectively, whereas the average times to showing Score-2 signs (paralysis, trembling, and coma) were 6.26 and 6.55 dpi, respectively. Body weight loss of more than 15% appeared at 5.82 and 6.42 dpi. The data provided here support the introduction of obvious neuronal signs combined with a body weight loss of ≥15% as a humane endpoint to reduce the time of animal suffering by approximately 4 days. Copyright © 2017 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  12. Potency Evaluation of Recombinant Human Erythropoietin in Brazil: Assessment of Reproducibility Using a Practical Approach

    Directory of Open Access Journals (Sweden)

    Michele Cardoso do Nascimento

    2015-08-01

    Full Text Available In this study, we compared the results of potency determination of recombinant human erythropoietin (rhEPO obtained between 2010 and 2012 by the National Institute of Quality Control in Health (INCQS/Fiocruz, i.e., the National Control Laboratory (NCL, and by a manufacturer of rhEPO. In total, 47 different batches of commercially prepared rhEPO (alpha isoform were analyzed. All results, including those of the control and warning limits, remained within the limits recommended by European Pharmacopoeia (Ph. Eur.. All relative error (RE values were less than ± 30%, wh ereas most were approximately ± 20%. Applying the Bland-Altman plot, only two of 47 values remained outside the limits of agreement (LA. In addition, agreement of potency determination between INCQS and the manufacturer coefficient of variation of reproducibility (% CVR was considered satisfactory. Taken together, our results demonstrate (i. the potency assay of rhEPO performed at INCQS, is standardized and controlled, (ii. the comparison of our results with those of the manufacturer, revealed an adequate inter-laboratory variation, and (iii. the critical appraisal proposed here appears to be a feasible tool to assess the reproducibility of biological activity, providing additional information regarding monitoring and production consistency to manufacturers and NCLs.

  13. Nano-titanium dioxide modulates the dermal sensitization potency of DNCB

    Directory of Open Access Journals (Sweden)

    Hussain Salik

    2012-05-01

    Full Text Available Abstract We determined the ability of a model nanoparticle (NP (titanium dioxide, TiO2 to modulate sensitization induced by a known potent dermal sensitizer (dinitrochlorobenzene using a variant of the local lymph node assay called lymph node proliferation assay. BALB/c mice received sub-cutaneous injections of vehicle (2.5 mM sodium citrate, TiO2 NPs (0.004, 0.04 or 0.4 mg/ml or pigment particles (0.04 mg/ml both stabilized in sodium citrate buffer at the base of each ear (2x50μl, before receiving dermal applications (on both ears of 2,4-Dinitrochlorobenzene (DNCB (2x25μl of 0.1% or its vehicle (acetone olive oil – AOO (4:1 on days 0, 1 and 2. On day 5, the stimulation index (SI was calculated as a ratio of 3HTdR incorporation in lymphocytes from DNBC-treated mice and AOO-treated controls. In a second experiment the EC3-value for DNCB (0 to 0.1% was assessed in the absence or presence of 0.04 mg/ml TiO2. In a third experiment, the lymphocyte subpopulations and the cytokine secretion profile were analyzed after TiO2 (0.04 mg/ml and DNCB (0.1% treatment. Injection of NPs in AOO-treated control mice did not have any effect on lymph node (LN proliferation. DNCB sensitization resulted in LN proliferation, which was further increased by injection of TiO2 NPs before DNCB sensitization. The EC3 of DNCB, with prior injection of vehicle control was 0.041%, while injection with TiO2 decreased the EC3 of DNCB to 0.015%. TiO2 NPs pre-treatment did not alter the lymphocyte subpopulations, but significantly increased the level of IL-4 and decreased IL-10 production in DNCB treated animals. In conclusion, our study demonstrates that administration of nano-TiO2 increases the dermal sensitization potency of DNCB, by augmenting a Th2 response, showing the immunomodulatory abilities of NPs.

  14. An overview of the report: Correlation between carcinogenic potency and the maximum tolerated dose: Implications for risk assessment

    International Nuclear Information System (INIS)

    Krewski, D.; Gaylor, D.W.; Soms, A.P.; Szyszkowicz, M.

    1993-01-01

    Current practice in carcinogen bioassay calls for exposure of experimental animals at doses up to and including the maximum tolerated dose (MTD). Such studies have been used to compute measures of carcinogenic potency such as the TD 50 as well as unit risk factors such as q 1 for predicting low-dose risks. Recent studies have indicated that these measures of carcinogenic potency are highly correlated with the MTD. Carcinogenic potency has also been shown to be correlated with indicators of mutagenicity and toxicity. Correlation of the MTDs for rats and mice implies a corresponding correlation in TD 50 values for these two species. The implications of these results for cancer risk assessment are examined in light of the large variation in potency among chemicals known to induce tumors in rodents. 119 refs., 2 figs., 4 tabs

  15. Antecedents of team potency and team effectiveness: an examination of goal and process clarity and servant leadership.

    Science.gov (United States)

    Hu, Jia; Liden, Robert C

    2011-07-01

    Integrating theories of self-regulation with team and leadership literatures, this study investigated goal and process clarity and servant leadership as 3 antecedents of team potency and subsequent team effectiveness, operationalized as team performance and organizational citizenship behavior. Our sample of 304 employees represented 71 teams in 5 banks. Results showed that team-level goal and process clarity as well as team servant leadership served as 3 antecedents of team potency and subsequent team performance and team organizational citizenship behavior. Furthermore, we found that servant leadership moderated the relationships between both goal and process clarity and team potency, such that the positive relationships between both goal and process clarity and team potency were stronger in the presence of servant leadership.

  16. Potency trends of Δ9-tetrahydrocannabinol, cannabidiol and cannabinol in cannabis in the Netherlands: 2005-15

    NARCIS (Netherlands)

    Niesink, Raymond J. M.; Rigter, Sander; Koeter, Maarten W.; Brunt, Tibor M.

    2015-01-01

    Between 2000 and 2005 the average percentage of Δ(9) -tetrahydrocannabinol (THC) in marijuana as sold in Dutch coffeeshops has increased substantially; the potency of domestic products (Nederwiet and Nederhasj) has particularly increased. In contrast with imported marijuana, Nederwiet hardly

  17. Potency trends of Δ9-tetrahydrocannabinol, cannabidiol and cannabinol in cannabis in the Netherlands: 2005-15.

    Science.gov (United States)

    Niesink, Raymond J M; Rigter, Sander; Koeter, Maarten W; Brunt, Tibor M

    2015-12-01

    Between 2000 and 2005 the average percentage of Δ(9) -tetrahydrocannabinol (THC) in marijuana as sold in Dutch coffeeshops has increased substantially; the potency of domestic products (Nederwiet and Nederhasj) has particularly increased. In contrast with imported marijuana, Nederwiet hardly contained any cannabidiol (CBD), a cannabinoid that is thought to offset some of the adverse effects of THC. In 2005, the THC content in Nederwiet was significantly lower than in 2004. This study investigates the further decrease or increase of cannabinoids in these cannabis products. From 2005 to 2015 five different cannabis products were bought anonymously in 50 coffeeshops that were selected randomly each year from all coffeeshops in the Netherlands. A total of 2126 cannabis samples were bought, consisting of 664 Nederwiet samples (most popular), 537 Nederwiet samples (supposed strongest varieties), 183 imported herbal cannabis samples, 140 samples of cannabis resin made of Nederwiet and 602 samples of imported cannabis resin. All samples were analysed chemically for their THC, CBD and cannabinol (CBN) content. Between 2005 and 2015, the mean potencies of the most popular and the strongest Nederwiet and of imported cannabis resin were 16.0±4.0%, 17.0±3,9% and 16.5±6.3%, respectively. Imported herbal cannabis (6.5±3.5%) and cannabis resin made from Nederwiet (30.2±16.4%) contained, respectively, less (β=-10.0, P<0.001) and more (β=13.7, P<0.001) THC than imported cannabis resin. Linear regression models were used to study the trends in THC of the different cannabis products over time. A marginal, but significant (P<0.001), overall decline of THC per year of 0.22% was found in all cannabis products. However, no significant difference was found between the five products in the THC linear trajectories across time. Of all the cannabis products, only imported cannabis resin contained a relatively high CBD/THC ratio (median 0.42). The average tetrahydrocannabinol (THC

  18. Potency determination of factor VIII and factor IX for new product labelling and postinfusion testing: challenges for caregivers and regulators.

    Science.gov (United States)

    Dodt, J; Hubbard, A R; Wicks, S J; Gray, E; Neugebauer, B; Charton, E; Silvester, G

    2015-07-01

    A workshop organized by the European Medicines Agency and the European Directorate for the Quality of Medicines and HealthCare was held in London, UK on November 28-29, 2013, to provide an overview of the current knowledge of the characterization of new factor VIII (FVIII) and factor IX (FIX) concentrates with respect to potency assays and testing of postinfusion material. The objective was to set the basis for regulatory authorities' discussion on the most appropriate potency assay for the individual products, and European Pharmacopoeia (Ph. Eur.) discussion on whether to propose revision of the Ph. Eur. monographs with respect to potency assays in the light of information on new FVIII and FIX concentrates. The workshop showed that for all products valid assays vs. the international concentrate standards were obtained and potency could be expressed in International Units. The Ph. Eur. chromogenic potency assay gave valid assay results which correlate with in vivo functionality of rFVIII products. For some modified rFVIII products and all modified rFIX products, one-stage clotting assay methods result in different potencies depending on the activated partial thromboplastin time reagent. As a consequence, monitoring of patients' postinfusion levels is challenging but it was pointed out that manufacturers are responsible for providing the users with appropriate information for use and laboratory testing of their product. Strategies to avoid misleading determination of patents' plasma levels, e.g. information on suitable assays, laboratory standards or correction factors were discussed. © 2015 John Wiley & Sons Ltd.

  19. Antagonistic targeting of the histamine H3 receptor decreases caloric intake in higher mammalian species.

    Science.gov (United States)

    Malmlöf, Kjell; Hastrup, Sven; Wulff, Birgitte Schellerup; Hansen, Barbara C; Peschke, Bernd; Jeppesen, Claus Bekker; Hohlweg, Rolf; Rimvall, Karin

    2007-04-15

    The main purpose of this study was to examine the effects of a selective histamine H(3) receptor antagonist, NNC 38-1202, on caloric intake in pigs and in rhesus monkeys. The compound was given intragastrically (5 or 15 mg/kg), to normal pigs (n=7) and subcutaneously (1 or 0.1mg/kg) to obese rhesus monkeys (n=9). The energy intake recorded following administration of vehicle to the same animals served as control for the effect of the compound. In addition, rhesus monkey and pig histamine H(3) receptors were cloned from hypothalamic tissues and expressed in mammalian cell lines. The in vitro antagonist potencies of NNC 38-1202 at the H(3) receptors were determined using a functional GTPgammaS binding assay. Porcine and human H(3) receptors were found to have 93.3% identity at the amino acid level and the close homology between the monkey and human H(3) receptors (98.4% identity) was confirmed. The antagonist potencies of NNC 38-1202 at the porcine, monkey and human histamine H(3) receptors were high as evidenced by K(i)-values being clearly below 20 nM, whereas the K(i)-value on the rat H(3) receptor was significantly higher (56+/-6.0 nM). NNC 38-1202, given to pigs in a dose of 15 mg/kg, produced a significant (p<0.05) reduction (55%) of calorie intake compared with vehicle alone, (132.6+/-10.0 kcal/kgday versus 59.7+/-10.2 kcal/kgday). In rhesus monkeys administration of 0.1 and 1mg/kg decreased (p<0.05) average calorie intakes by 40 and 75%, respectively. In conclusion, the present study demonstrates that antagonistic targeting of the histamine H(3) receptor decreases caloric intake in higher mammalian species.

  20. Screening for Endophytic Fungi from Turmeric Plant (Curcuma longa L.) of Sukabumi and Cibinong with Potency as Antioxidant Compounds Producer.

    Science.gov (United States)

    Bustanussalam; Rachman, Fauzy; Septiana, Eris; Lekatompessy, Sylvia J R; Widowati, Tiwit; Sukiman, Harmastini I; Simanjuntak, Partomuan

    2015-01-01

    Potency of medicinal plant is related to microorganisms lived in the plant tissue. Those microorganisms are known as endophytic microbes that live and form colonies in the plant tissue without harming its host. Each plant may contains several endophytic microbes that produce biological compounds or secondary metabolites due to co-evolution or genetic transfer from the host plant to endophytic microbes. Endophytic fungi research done for turmeric plant (Curcuma longa L.) gave 44 isolated fungi as results. Those 44 fungi isolated were fermented in Potato Dextrose Broth (PDB) media, filtered, extracted with ethylacetate and then were analyzed by Thin Layer Chromatography (TLC) method and tested for their antioxidant activity by radical scavenging method. The antioxidant activity of the ethylacetate filtrate extracts either from Sukabumi or Cibinong were higher than the biomass extracts. There were 6 fungi that showed antioxidant activities over 65%, i.e., with code name K.Cl.Sb.R9 (93.58%), K.Cl.Sb.A11 (81.49%), KCl.Sb.B1 (78.81%), KCl.Sb.R11 (71.67%) and K.Cl.Sb.A12 (67.76%) from Sukabumi and K.Cl.Cb.U1 (69.27%) from Cibinong. These results showed that bioproduction by endophytic microbes can gave potential antioxidant compounds.

  1. Antibacterial activity of Thymoquinone, an active principle of Nigella sativa and its potency to prevent bacterial biofilm formation

    Directory of Open Access Journals (Sweden)

    Bakhrouf Amina

    2011-04-01

    Full Text Available Abstract Background Thymoquinone is an active principle of Nigella sativa seed known as "Habbah Al-Sauda" in Arabic countries and "Sinouj" in Tunisia. Bacterial biofilms tend to exhibit significant tolerance to antimicrobials drugs during infections. Methods The antibacterial activity of Thymoquinone (TQ and its biofilm inhibition potencies were investigated on 11 human pathogenic bacteria. The growth and development of the biofilm were assessed using the crystal violet (CV and the 2, 3-bis [2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT reduction assay. Results TQ exhibited a significant bactericidal activity against the majority of the tested bacteria (MICs values ranged from 8 to 32 μg/ml especially Gram positive cocci (Staphylococcus aureus ATCC 25923 and Staphylococcus epidermidis CIP 106510. Crystal violet assay demonstrated that the minimum biofilm inhibition concentration (BIC50 was reached with 22 and 60 μg/ml for Staphylococcus aureus ATCC 25923 and Staphylococcus epidermidis CIP 106510 respectively. In addition our data revealed that cells oxidative activity was influenced by TQ supplementation. In the same way, TQ prevented cell adhesion to glass slides surface. Conclusion The ability of TQ to prevent biofilm formation warrants further investigation to explore its use as bioactive substances with antibiofilm potential.

  2. Biosorption of Congo Red from aqueous solution by Bacillus weihenstephanensis RI12; effect of SPB1 biosurfactant addition on biodecolorization potency.

    Science.gov (United States)

    Mnif, Inès; Fendri, Raouia; Ghribi, Dhouha

    2015-01-01

    Bacillus weihenstephanensis RI12, isolated from hydrocarbon contaminated soil, was assessed for Congo Red bio-treatment potency. Results suggested the potential of this bacterium for use in effective treatment of Congo Red contaminated wastewaters under shaking conditions at acidic and neutral pH value. The strain could tolerate higher doses of dyes as it could decolorize up to 1,000 mg/l of Congo Red. When used as microbial surfactant to enhance Congo Red biodecolorization, Bacillus subtilis SPB1-derived lipopeptide accelerated the decolorization rate and maximized the decolorization efficiency at an optimal concentration of biosurfactant of about 0.075%. Studies ensured that Congo Red removal by this strain could be due to an adsorption phenomena. Germination potencies of tomato seeds using the treated dyes under different conditions showed the efficient biotreatment of the azo dye Congo Red especially with the addition of SPB1 biosurfactant. To conclude, the addition of SPB1 bioemulsifier reduced energy costs by reducing the effective decolorization period; the biosurfactant stimulated bacterial decolorization method may provide a highly efficient, inexpensive and time-saving procedure in the treatment of textile effluents.

  3. Soluble HIV-1 envelope immunogens derived from an elite neutralizer elicit cross-reactive V1V2 antibodies and low potency neutralizing antibodies.

    Directory of Open Access Journals (Sweden)

    Sara Carbonetti

    Full Text Available We evaluated four gp140 Envelope protein vaccine immunogens that were derived from an elite neutralizer, subject VC10042, whose plasma was able to potently neutralize a wide array of genetically distinct HIV-1 isolates. We sought to determine whether soluble Envelope proteins derived from the viruses circulating in VC10042 could be used as immunogens to elicit similar neutralizing antibody responses by vaccination. Each gp140 was tested in its trimeric and monomeric forms, and we evaluated two gp140 trimer vaccine regimens in which adjuvant was supplied at all four immunizations or at only the first two immunizations. Interestingly, all four Envelope immunogens elicited high titers of cross-reactive antibodies that recognize the variable regions V1V2 and are potentially similar to antibodies linked with a reduced risk of HIV-1 acquisition in the RV144 vaccine trial. Two of the four immunogens elicited neutralizing antibody responses that neutralized a wide array of HIV-1 isolates from across genetic clades, but those responses were of very low potency. There were no significant differences in the responses elicited by trimers or monomers, nor was there a significant difference between the two adjuvant regimens. Our study identified two promising Envelope immunogens that elicited anti-V1V2 antibodies and broad, but low potency, neutralizing antibody responses.

  4. Enhanced bactericidal potency of nanoliposomes by modification of the fusion activity between liposomes and bacterium

    Directory of Open Access Journals (Sweden)

    Ma YF

    2013-06-01

    amount of negative charges in fluid liposomes reduces fluid liposomes-bacteria fusion when tested without calcium cations due to electric repulsion, but addition of calcium cations brings the fusion level of fluid liposomes to similar or higher levels. Among the negative phospholipids examined, DMPA gave the highest degree of fusion, DMPS and DMPG had intermediate fusion levels, and PI resulted in the lowest degree of fusion. Furthermore, the fluid liposomal encapsulated tobramycin was prepared, and the bactericidal effect occurred more quickly when bacteria were cultured with liposomal encapsulated tobramycin. Conclusion: The bactericidal potency of fluid liposomes is dramatically enhanced with respect to fusion ability when the fusogenic lipid, DOPE, is included. Regardless of changes in liposome composition, fluid liposomes-bacterium fusion is universally enhanced by calcium ions. The information obtained in this study will increase our understanding of fluid liposomal action mechanisms, and help in optimizing the new generation of fluid liposomal formulations for the treatment of pulmonary bacterial infections. Keywords: liposomes, fusion, bacteria, Pseudomonas aeruginosa, lipid composition

  5. Predictive modelling of 2-year potency outcomes using a novel 90-day erection fullness scale after robot-assisted radical prostatectomy.

    Science.gov (United States)

    Huynh, Linda M; Osann, Kathryn; Skarecky, Douglas; Ahlering, Thomas E

    2018-03-09

    To introduce a patient-reported erection fullness scale (%fullness) after robot-assisted radical prostatectomy (RARP) as a qualitative adjunct to the five-item version of the International Index of Erectile Function (IIEF-5) and as a 90-day predictor of 2-year potency outcomes. Prospective data were collected from 540 men with preoperative IIEF-5 scores of 22-25 who underwent RARP by a single surgeon, and of whom 299 had complete data at all time points up to 2 years. In addition to standard assessment tools (IIEF-5 and erections sufficient for intercourse [ESI]), the men were asked to 'indicate the fullness you are able to achieve in erections compared to before surgery?' (range: 0-100%). The primary outcome was prediction of potency (defined as ESI) at 24 months, based on 90-day %fullness tertile (0-24%, 25-74% and 75-100%). A total of 299 men with complete follow-up were included in the study. Significant predictors of 24-month potency included age, body mass index, pathological stage, nerve-sparing status and %fullness tertiles. When the men (preoperative IIEF-5 score 22-25) were assessed at 90 days after RARP, 181/299 (61%) had erections inadequate for intercourse. If IIEF-5 scores of 1-6 were used, 142/181 men (78%) would be targeted for early intervention. By contrast, if 0-24% fullness was used, 88/181 men (49%) would be targeted. If both the IIEF-5 score and %fullness were used, this would be reduced to 77/181 men (43%). We introduce %fullness as a qualitative adjunct to the IIEF-5 score, and separately as a 90-day predictor of 2-year potency recovery. This initial report is hypothesis-generating, such that the use of %fullness enables the identification of men who are most likely to benefit from early, secondary intervention. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

  6. Potency of sponge-associated bacteria producing bioactive compounds as biological control of vibriosis on shrimp

    Directory of Open Access Journals (Sweden)

    Adityawati Fajar Rini

    2017-07-01

    Full Text Available ABSTRACT The aims of this study were to obtain sponge-associated bacteria as biocontrol to inhibit vibriosis in vitro and in vivo, to identify the bacterial isolates based on 16S-rRNA gene, and to detect the presence of nonribosomal peptide synthetase (NRPS, and polyketide synthase (PKS genes to prove its ability of bioactive compounds synthesis. Aaptos sp. and Hyrtios sp. sponges were collected from Pramuka Island, Jakarta. The isolation using sea water complete (SWC and  zobel marine agar (ZMA medium obtained 174 isolates. A total 69 isolates were screened successfully based on their antibacterial activity. 47 isolates showed negative haemolysis through hemolytic assays. The pathogenicity test used twelve selected isolates that have a broad spectrum of antibacterial activity and haemolysis negative. The result of pathogenicity test showed  that 12 isolates were not pathogenic to the shrimp post larvae with no significantly different (P>0.05 between treatment and negative control. Results of challenge test with Vibrio harveyi have a significant difference survival (70±5.0–90±0.0% (P<0.05 compared with positive control (38.3±2.9%. Genetic analysis based on 16S-rRNA revealed the groups of three genera belonged to Pseudomonas, Staphylococcus, and Alcaligenes. Based on amplification of NRPS and PKS genes, four bacterial isolates have been detected to have only NRPS gene, one isolate has only PKS, and one isolate has both genes. The results indicate that the potency of six sponge-associated bacteria as bioactive compounds producers. Keywords: NRPS, PKS, anti-vibriosis, Pacific white shrimp  ABSTRAK Penelitian ini bertujuan untuk memperoleh isolat bakteri asosiasi spons yang mempunyai kemampuan dalam menghambat vibriosis secara in vitro, in vivo dan mendeteksi gen 16S-rRNA, nonribosomal peptide synthase (NRPS serta polyketide synthase (PKS untuk memastikan kemampuan mensintesis senyawa bioaktif. Spons Aaptos sp. dan Hyrtios sp. berhasil

  7. An epidermal equivalent assay for identification and ranking potency of contact sensitizers

    Energy Technology Data Exchange (ETDEWEB)

    Gibbs, Susan, E-mail: S.Gibbs@VUMC.nl [Department of Dermatology, VU University Medical Centre, Dept of Oral Cell Biology, ACTA, Amsterdam (Netherlands); Corsini, Emanuela [Laboratory of Toxicology, DiSFeB, Università degli Studi di Milano (Italy); Spiekstra, Sander W. [Department of Dermatology, VU University Medical Centre, Dept of Oral Cell Biology, ACTA, Amsterdam (Netherlands); Galbiati, Valentina [Laboratory of Toxicology, DiSFeB, Università degli Studi di Milano (Italy); Fuchs, Horst W. [CellSystems GmbH, Troisdorf (Germany); DeGeorge, George; Troese, Matthew [MB Research Labs, Spinnerstown, PA (United States); Hayden, Patrick; Deng, Wei [MatTek Corporation, Ashland, MA (United States); Roggen, Erwin [3Rs Management and Consultancy (Denmark)

    2013-10-15

    The purpose of this study was to explore the possibility of combining the epidermal equivalent (EE) potency assay with the assay which assesses release of interleukin-18 (IL-18) to provide a single test for identification and classification of skin sensitizing chemicals, including chemicals of low water solubility or stability. A protocol was developed using different 3D-epidermal models including in house VUMC model, epiCS® (previously EST1000™), MatTek EpiDerm™ and SkinEthic™ RHE and also the impact of different vehicles (acetone:olive oil 4:1, 1% DMSO, ethanol, water) was investigated. Following topical exposure for 24 h to 17 contact allergens and 13 non-sensitizers a robust increase in IL-18 release was observed only after exposure to contact allergens. A putative prediction model is proposed from data obtained from two laboratories yielding 95% accuracy. Correlating the in vitro EE sensitizer potency data, which assesses the chemical concentration which results in 50% cytotoxicity (EE-EC{sub 50}) with human and animal data showed a superior correlation with human DSA{sub 05} (μg/cm{sup 2}) data (Spearman r = 0.8500; P value (two-tailed) = 0.0061) compared to LLNA data (Spearman r = 0.5968; P value (two-tailed) = 0.0542). DSA{sub 05} = induction dose per skin area that produces a positive response in 5% of the tested population Also a good correlation was observed for release of IL-18 (SI-2) into culture supernatants with human DSA{sub 05} data (Spearman r = 0.8333; P value (two-tailed) = 0.0154). This easily transferable human in vitro assay appears to be very promising, but additional testing of a larger chemical set with the different EE models is required to fully evaluate the utility of this assay and to establish a definitive prediction model. - Highlights: • A potential epidermal equivalent assay to label and classify sensitizers • Il-18 release distinguishes sensitizers from non sensitizers • IL-18 release can rank sensitizer potency

  8. Synthesis of 3-alkyl enol mimics inhibitors of type II dehydroquinase: factors influencing their inhibition potency.

    Science.gov (United States)

    Blanco, Beatriz; Sedes, Antía; Peón, Antonio; Lamb, Heather; Hawkins, Alastair R; Castedo, Luis; González-Bello, Concepción

    2012-05-14

    Several 3-alkylaryl mimics of the enol intermediate in the reaction catalyzed by type II dehydroquinase were synthesized to investigate the effect on the inhibition potency of replacing the oxygen atom in the side chain by a carbon atom. The length and the rigidity of the spacer was also studied. The inhibitory properties of the reported compounds against type II dehydroquinase from Mycobacterium tuberculosis and Helicobacter pylori are also reported. The binding modes of these analogs in the active site of both enzymes were studied by molecular docking using GOLD 5.0 and dynamic simulations studies.

  9. THE ANTIGENIC POTENCY OF EPIDEMIC INFLUENZA VIRUS FOLLOWING INACTIVATION BY ULTRAVIOLET RADIATION

    Science.gov (United States)

    Salk, Jonas E.; Lavin, G. I.; Francis, Thomas

    1940-01-01

    A study of the antigenic potency of influenza virus inactivated by ultraviolet radiation has been made. Virus so inactivated is still capable of functioning as an immunizing agent when given to mice by the intraperitoneal route. In high concentrations inactivated virus appears to be nearly as effective as active virus but when quantitative comparisons of the immunity induced by different dilutions are made, it is seen that a hundredfold loss in immunizing capacity occurs during inactivation. Virus in suspensions prepared from the lungs of infected mice is inactivated more rapidly than virus in tissue culture medium. A standard for the comparison of vaccines of epidemic influenza virus is proposed. PMID:19871057

  10. Sanctioning Large-Scale Domestic Cannabis Production - Potency, Yield and Professionalism

    DEFF Research Database (Denmark)

    Møller, Kim; Lindholst, Christian

    2014-01-01

    Domestically cultivated cannabis, referred to as sinsemilla, constitutes a growing share of the illicit drug markets in the Scandinavian countries. In this study we present forensic evidence of THC content in sinsemilla and resin confiscated by the Danish police from 2008 to 2012. The purpose...... that courts do not apply a yield-percentage estimate. The specificities of domestic cannabis cultivation also relate to the sanction criteria „professionalism”. Firstly, the number of plants found can provide for calculation of an aggregate quantum. Secondly, this can be related to the formal quantum......-scale cannabis cases would improve by applying a 1:1 potency level between sinsemilla and resin....

  11. An epidermal equivalent assay for identification and ranking potency of contact sensitizers

    International Nuclear Information System (INIS)

    Gibbs, Susan; Corsini, Emanuela; Spiekstra, Sander W.; Galbiati, Valentina; Fuchs, Horst W.; DeGeorge, George; Troese, Matthew; Hayden, Patrick; Deng, Wei; Roggen, Erwin

    2013-01-01

    The purpose of this study was to explore the possibility of combining the epidermal equivalent (EE) potency assay with the assay which assesses release of interleukin-18 (IL-18) to provide a single test for identification and classification of skin sensitizing chemicals, including chemicals of low water solubility or stability. A protocol was developed using different 3D-epidermal models including in house VUMC model, epiCS® (previously EST1000™), MatTek EpiDerm™ and SkinEthic™ RHE and also the impact of different vehicles (acetone:olive oil 4:1, 1% DMSO, ethanol, water) was investigated. Following topical exposure for 24 h to 17 contact allergens and 13 non-sensitizers a robust increase in IL-18 release was observed only after exposure to contact allergens. A putative prediction model is proposed from data obtained from two laboratories yielding 95% accuracy. Correlating the in vitro EE sensitizer potency data, which assesses the chemical concentration which results in 50% cytotoxicity (EE-EC 50 ) with human and animal data showed a superior correlation with human DSA 05 (μg/cm 2 ) data (Spearman r = 0.8500; P value (two-tailed) = 0.0061) compared to LLNA data (Spearman r = 0.5968; P value (two-tailed) = 0.0542). DSA 05 = induction dose per skin area that produces a positive response in 5% of the tested population Also a good correlation was observed for release of IL-18 (SI-2) into culture supernatants with human DSA 05 data (Spearman r = 0.8333; P value (two-tailed) = 0.0154). This easily transferable human in vitro assay appears to be very promising, but additional testing of a larger chemical set with the different EE models is required to fully evaluate the utility of this assay and to establish a definitive prediction model. - Highlights: • A potential epidermal equivalent assay to label and classify sensitizers • Il-18 release distinguishes sensitizers from non sensitizers • IL-18 release can rank sensitizer potency • EC50 (chemical

  12. Acceleromyography and mechanomyography for establishing potency of neuromuscular blocking agents: a randomized-controlled trial

    DEFF Research Database (Denmark)

    Claudius, C; Viby-Mogensen, J; Skovgaard, Lene Theil

    2009-01-01

    ) for this purpose. The aim of this study was to compare AMG and MMG for establishing dose-response relationship and potency, using rocuronium as an example. METHODS: We included 40 adult patients in this randomized-controlled single-dose response study. Anaesthesia was induced and maintained with propofol...... and opioid. Neuromuscular blockade was induced with rocuronium 100, 150, 200 or 250 microg/kg. Neuromuscular monitoring was performed with AMG (TOF-Watch SX) with pre-load (Hand Adapter) at one arm and MMG (modified TOF-Watch SX) on the other, using 0.1 Hz single twitch stimulation. Dose...

  13. Potency of a novel saw palmetto ethanol extract, SPET-085, for inhibition of 5alpha-reductase II.

    Science.gov (United States)

    Pais, Pilar

    2010-08-01

    The nicotinamide adenine dinucleotide phosphate (NADPH)-dependent membrane protein 5alpha-reductase irreversibly catalyses the conversion of testosterone to the most potent androgen, 5alpha-dihydrotestosterone (DHT). In humans, two 5alpha-reductase isoenyzmes are expressed: type I and type II. Type II is found primarily in prostate tissue. Saw palmetto extract (SPE) has been widely used for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH). The mechanisms of the pharmacological effects of SPE include the inhibition of 5alpha-reductase, among other actions. Clinical studies of SPE have been equivocal, with some showing significant results and others not. These inconsistent results may be due, in part, to varying bioactivities of the SPE used in the studies. The aim of the present study was to determine the in vitro potency of a novel saw palmetto ethanol extract (SPET-085), an inhibitor of the 5alpha-reductase isoenzyme type II, in a cell-free test system. On the basis of the enzymatic conversion of the substrate androstenedione to the 5alpha-reduced product 5alpha-androstanedione, the inhibitory potency was measured and compared to those of finasteride, an approved 5alpha-reductase inhibitor. SPET-085 concentration-dependently inhibited 5alpha-reductase type II in vitro (IC(50)=2.88+/-0.45 microg/mL). The approved 5alpha-reductase inhibitor, finasteride, tested as positive control, led to 61% inhibition of 5alpha-reductase type II. SPET-085 effectively inhibits the enzyme that has been linked to BPH, and the amount of extract required for activity is very low compared to data reported for other extracts. It can be concluded from data in the literature that SPET-085 is as effective as a hexane extract of saw palmetto that exhibited the highest levels of bioactivity, and is more effective than other SPEs tested. This study confirmed that SPET-085 has prostate health-promoting bioactivity that also corresponds favorably to

  14. NanoDisk containing super aggregated amphotericin B: a high therapeutic index antifungal formulation with enhanced potency

    Directory of Open Access Journals (Sweden)

    Burgess BL

    2013-12-01

    Full Text Available Braydon L Burgess,1,2 Yumin He,1 Mandie M Baker,1,2 Bing Luo,2 Stephen F Carroll,2 Trudy M Forte,2 Michael N Oda11Children's Hospital Oakland Research Institute, Oakland, CA, USA; 2Lypro Biosciences, Berkeley, CA, USAObjectives: NanoDisk–amphotericin B (ND-AMB is a protein-phospholipid bioparticle containing a “super aggregate” form of antifungal AMB. While lipid-based formulations of AMB, including liposomal AMB (L-AMB, are safer than the deoxycholate (DOC solubilized form (DOC-AMB, the potency of lipid-based formulations is attenuated. We have developed an AMB-based therapy that is both well tolerated and fully efficacious.Methods: Potency was determined using broth culture growth-inhibition assays and candidacidal kinetics by quantitative culture plating. Toxicology studies were performed in healthy mice. Efficacy was assessed using both immune-competent and leukopenic murine models of systemic Candida albicans infection.Results: ND-AMB C. albicans and Aspergillus fumigatus minimum inhibitory concentrations were fourfold and sixfold lower, respectively, than that observed for L-AMB. ND-AMB exhibited candidacidal activity at 0.125 mg/L, 16-fold lower than L-AMB. In mice, ND-AMB produced no statistically significant kidney or liver toxicity at 15 mg/kg, the highest dose tested. When evaluated in immune-competent mice infected with C. albicans, ND-AMB was at least as effective as DOC-AMB or L-AMB. In a leukopenic model of candidiasis, the 50% effective dose of ND-AMB was around threefold lower than L-AMB.Conclusion: These results indicate that ND-AMB exhibits a more favorable safety profile while maintaining uncompromised antifungal properties compared to both DOC-AMB and L-AMB. ND-AMB is a promising therapy for the treatment of invasive fungal infections.Keywords: nanoparticles, infectious diseases, drug delivery, candidiasis, apolipoprotein A-I

  15. Potency of maternal folic acid supplementation on gamma irradiation- induced histological and embryological anomalies in albino rats

    International Nuclear Information System (INIS)

    Rezk, R.G.; Ibrahim, M.F.

    2006-01-01

    Folic acid, a member of the water-soluble vitamin B group, is emerged as an important nutritional factor especially during the course of pregnancy. It is rapidly absorbed from the proximal part of small intestine, distributed to the body tissues, stored in the liver and actively concentrated in the cerebrospinal fluid. The objective of this study was to evaluate the potency of maternal folic acid supplementation in ameliorating the maternal and fetal detrimental impacts of gamma irradiation. Folic acid, at a dose level of 4 mg/Kg body weight was daily administered via an oral stomach tube to pregnant adult albino rats from the 1st to the 20 th day of pregnancy, while mothers were subjected to gamma irradiation at the dose of 3 Gy on day 10 of gestation during the sensitive period of organogenesis. Experimental investigations carried out 1 day prior to parturition have demonstrated that folic acid intake throughout the whole gestational period had significantly diminished the deleterious histopathological disorders in large intestine, liver and uterus of irradiated mothers. Concomitantly, folic acid has been able to enfeeble the hazardous teratological effects of radiation including mainly the fetal intrauterine lethality, developmental delay and prominent morphological deformities. Conclusively, folic acid was found to offer protection during pregnancy against radiation injury, thus was capable of modulating the histopathological impacts of the studied maternal body organs and suppressing the embryonic mortality rates and serious fetal malformations induced by radiation

  16. Methylphenidate and cocaine have a similar in vivo potency to block dopamine transporters in the human brain

    International Nuclear Information System (INIS)

    Volkow, N.D.

    1999-01-01

    The reinforcing effects of cocaine and methylphenidate have been linked to their ability to block dopamine transporters (DAT). Though cocaine and methylphenidate have similar in vitro affinities for DAT the abuse of methylphenidate in humans is substantially lower than of cocaine. To test if differences in in vivo potency at the DAT between these two drugs could account for the differences in their abuse liability the authors compared the levels of DAT occupancies that they had previously reported separately for intravenous methylphenidate in controls and for intravenous cocaine in cocaine abusers. DAT occupancies were measured with Positron Emission Tomography using [ 11 C]cocaine, as a DAT ligand, in 8 normal controls for the methylphenidate study and in 17 active cocaine abusers for the cocaine study. The ratio of the distribution volume of [ 11 C]cocaine in striatum to that in cerebellum, which corresponds to Bmax/Kd+1, was used as measure of DAT availability. Parallel measures were obtained to assess the cardiovascular effects of these two drugs. Methylphenidate and cocaine produced comparable dose-dependent blockage of DAT with an estimated ED 50 for methylphenidate of 0.07 mg/kg and for cocaine of 0.13 mg/kg. Both drugs induced similar increases in heart rate and blood pressure but the duration of the effects were significantly longer for methylphenidate than for cocaine

  17. In ovo injection of prebiotics and synbiotics affects the digestive potency of the pancreas in growing chickens.

    Science.gov (United States)

    Pruszynska-Oszmalek, E; Kolodziejski, P A; Stadnicka, K; Sassek, M; Chalupka, D; Kuston, B; Nogowski, L; Mackowiak, P; Maiorano, G; Jankowski, J; Bednarczyk, M

    2015-08-01

    The purpose of the study was to examine the effect of 2 prebiotics and 2 synbiotics on the digestive potency of pancreas in 1-, 3-, 7-, 14-, 21-, and 34-day-old cockerels. Prebiotics (inulin and Bi²tos) and synbiotics (inulin + Lactococcus lactis subsp. lactis and Bi²tos + Lactococcus lactis subsp. cremoris) were injected in ovo into the air cell on the 12th d embryonic development. Their application increased the activity of amylase, lipase, and trypsin in the pancreas. The most pronounced changes were observed at the end of the investigated rearing period (d 34). The strongest stimulative effects on amylase were shown by both synbiotics, on lipase synbiotic Bi²tos + Lactococcus lactis subsp. cremoris, and on trypsin all the used prebiotics and synbiotics. Simultaneously, neither the absolute nor the relative mass of the pancreas in comparison to control group were changed. Also, the injected in ovo compounds did not cause a deterioration in the posthatching condition of the chicken liver, as determined by measurement of the activity of marker enzymes in the blood (alanine aminotransferase and aspartate aminotransferase). Treatment with the prebiotics and synbiotics did not change the feed conversion ratio but Bi²tos (galacto-oligosaccharide) and inulin (fructan) + Lactococcus lactis subsp. lactis significantly increased final BW. © 2015 Poultry Science Association Inc.

  18. Clomiphene and Its Isomers Block Ebola Virus Particle Entry and Infection with Similar Potency: Potential Therapeutic Implications.

    Science.gov (United States)

    Nelson, Elizabeth A; Barnes, Alyson B; Wiehle, Ronald D; Fontenot, Gregory K; Hoenen, Thomas; White, Judith M

    2016-08-02

    The 2014 outbreak of Ebola virus (EBOV) in Western Africa highlighted the need for anti-EBOV therapeutics. Clomiphene is a U.S. Food and Drug Administration (FDA)-approved drug that blocks EBOV entry and infection in cells and significantly protects EBOV-challenged mice. As provided, clomiphene is, approximately, a 60:40 mixture of two stereoisomers, enclomiphene and zuclomiphene. The pharmacokinetic properties of the two isomers vary, but both accumulate in the eye and male reproductive tract, tissues in which EBOV can persist. Here we compared the ability of clomiphene and its isomers to inhibit EBOV using viral-like particle (VLP) entry and transcription/replication-competent VLP (trVLP) assays. Clomiphene and its isomers inhibited the entry and infection of VLPs and trVLPs with similar potencies. This was demonstrated with VLPs bearing the glycoproteins from three filoviruses (EBOV Mayinga, EBOV Makona, and Marburg virus) and in two cell lines (293T/17 and Vero E6). Visual problems have been noted in EBOV survivors, and viral RNA has been isolated from semen up to nine months post-infection. Since the clomiphene isomers accumulate in these affected tissues, clomiphene or one of its isomers warrants consideration as an anti-EBOV agent, for example, to potentially help ameliorate symptoms in EBOV survivors.

  19. Clomiphene and Its Isomers Block Ebola Virus Particle Entry and Infection with Similar Potency: Potential Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Elizabeth A. Nelson

    2016-08-01

    Full Text Available The 2014 outbreak of Ebola virus (EBOV in Western Africa highlighted the need for anti-EBOV therapeutics. Clomiphene is a U.S. Food and Drug Administration (FDA-approved drug that blocks EBOV entry and infection in cells and significantly protects EBOV-challenged mice. As provided, clomiphene is, approximately, a 60:40 mixture of two stereoisomers, enclomiphene and zuclomiphene. The pharmacokinetic properties of the two isomers vary, but both accumulate in the eye and male reproductive tract, tissues in which EBOV can persist. Here we compared the ability of clomiphene and its isomers to inhibit EBOV using viral-like particle (VLP entry and transcription/replication-competent VLP (trVLP assays. Clomiphene and its isomers inhibited the entry and infection of VLPs and trVLPs with similar potencies. This was demonstrated with VLPs bearing the glycoproteins from three filoviruses (EBOV Mayinga, EBOV Makona, and Marburg virus and in two cell lines (293T/17 and Vero E6. Visual problems have been noted in EBOV survivors, and viral RNA has been isolated from semen up to nine months post-infection. Since the clomiphene isomers accumulate in these affected tissues, clomiphene or one of its isomers warrants consideration as an anti-EBOV agent, for example, to potentially help ameliorate symptoms in EBOV survivors.

  20. Evaluation of anxiolytic potency of essential oil and S-(+-linalool from Cinnamomum osmophloeum ct. linalool leaves in mice

    Directory of Open Access Journals (Sweden)

    Bing-Ho Cheng

    2015-01-01

    Full Text Available Cinnamomum osmophloeum ct. linalool (土肉桂 tǔ ròu guì is one chemotype of the indigenous cinnamons in Taiwan. This study examined the anxiolytic potency of leaf essential oil (LEO from C. osmophloeum ct. linalool and its main constituent on 4-week ICR mice using an open field test (OFT, a light–dark test (LDT and an elevated plus maze test (EPT. After oral administration of corn oil, LEO (250 mg/kg and 500 mg/kg, S-(+-linalool (500 mg/kg, R-(−-linalool (500 mg/kg, and trazodone hydrochloride (75 mg/kg for 14 days, the anxiolytic effects on mice behavior were evaluated. The results showed that LEO from C. osmophloeum ct. linalool leaves and S-(+-linalool can significantly increase the time mice remained in the center area of the OFT, the illuminated area of the LDT and the open arms of the EPT without any side effects affecting motor activity, indicating excellent anxiolytic responses. Furthermore, results from the measurements of monoamines in mice brain revealed decreases in serotonin, dopamine, and norepinephrine, which are consistent with their anxiolytic effects in animal models. The findings obtained suggest that LEO from C. osmophloeum ct. linalool and its major compound, S-(+-linalool, possess anxiolytic properties without any side effects and thus support their potential use in treatment of anxiety disorders.

  1. The Low Pressure Gas Effects On The Potency Of An Electron Beam On Ceramic Fabric Materials For Space Welding

    Science.gov (United States)

    Nunes, Arthur C., Jr.; Fragomeni, James M.; Munafo, Paul M. (Technical Monitor)

    2001-01-01

    This investigation was undertaken to evaluate if molten metal or electron beam impingement could damage or burn through the fabric of the astronauts Extravehicular Mobility Unit (EMU) during electron beam welding exercises performed in space. An 8 kilovolt electron beam with a current in the neighborhood of 100 milliamps from the Ukrainian space welding "Universal Hand Tool" burned holes in Nextel AF-62 ceramic cloth designed to withstand temperatures up to 1427 C. The burnthrough time was on the order of 8 seconds at standoff distances between UHT and cloth ranging from 6 to 24 inches. At both closer (2") and farther (48") standoff distances the potency of the beam against the cloth declined and the burnthrough time went up significantly. Prior to the test it had been expected that the beam would lay down a static charge on the cloth and be deflected without damaging the cloth. The burnthrough is thought to be an effect of partial transmission of beam power by a stream of positive ions generated by the high voltage electron beam from contaminant gas in the "vacuum" chamber. A rough quantitative theoretical computation appears to substantiate this possibility.

  2. Potency of maternal folic acid supplementation on gamma irradiation- induced histological and embryological anomalies in albino rats

    Energy Technology Data Exchange (ETDEWEB)

    Rezk, R G [Health Rad. Res., NCRRT, Cairo (Egypt); Ibrahim, M F [Rad. Biology Dept., NCRRT, Cairo (Egypt)

    2006-07-01

    Folic acid, a member of the water-soluble vitamin B group, is emerged as an important nutritional factor especially during the course of pregnancy. It is rapidly absorbed from the proximal part of small intestine, distributed to the body tissues, stored in the liver and actively concentrated in the cerebrospinal fluid. The objective of this study was to evaluate the potency of maternal folic acid supplementation in ameliorating the maternal and fetal detrimental impacts of gamma irradiation. Folic acid, at a dose level of 4 mg/Kg body weight was daily administered via an oral stomach tube to pregnant adult albino rats from the 1st to the 20 th day of pregnancy, while mothers were subjected to gamma irradiation at the dose of 3 Gy on day 10 of gestation during the sensitive period of organogenesis. Experimental investigations carried out 1 day prior to parturition have demonstrated that folic acid intake throughout the whole gestational period had significantly diminished the deleterious histopathological disorders in large intestine, liver and uterus of irradiated mothers. Concomitantly, folic acid has been able to enfeeble the hazardous teratological effects of radiation including mainly the fetal intrauterine lethality, developmental delay and prominent morphological deformities. Conclusively, folic acid was found to offer protection during pregnancy against radiation injury, thus was capable of modulating the histopathological impacts of the studied maternal body organs and suppressing the embryonic mortality rates and serious fetal malformations induced by radiation.

  3. Bridging the Gap Between Validation and Implementation of Non-Animal Veterinary Vaccine Potency Testing Methods

    Directory of Open Access Journals (Sweden)

    Alistair Currie

    2011-11-01

    Full Text Available In recent years, technologically advanced high-throughput techniques have been developed that replace, reduce or refine animal use in vaccine quality control tests. Following validation, these tests are slowly being accepted for use by international regulatory authorities. Because regulatory acceptance itself has not guaranteed that approved humane methods are adopted by manufacturers, various organizations have sought to foster the preferential use of validated non-animal methods by interfacing with industry and regulatory authorities. After noticing this gap between regulation and uptake by industry, we began developing a paradigm that seeks to narrow the gap and quicken implementation of new replacement, refinement or reduction guidance. A systematic analysis of our experience in promoting the transparent implementation of validated non-animal vaccine potency assays has led to the refinement of our paradigmatic process, presented here, by which interested parties can assess the local regulatory acceptance of methods that reduce animal use and integrate them into quality control testing protocols, or ensure the elimination of peripheral barriers to their use, particularly for potency and other tests carried out on production batches.

  4. Immunotropic potency of microwave fields: preliminary studies on immunocompetent cells exposed in vitro

    International Nuclear Information System (INIS)

    Stankiewicz, W.; Dabrowski, M.P.; Sobiczewska, E.; Kubacki, R.; Szmigielski, S.

    2006-01-01

    Exposure in radiofrequency (RF) and microwave (MW) fields can influence the function of the immune system, but the data available on the immunotropic potency of RF/MW radiation are still full of uncertainties and controversies. In the available literature there exist no reports on complex assessment of function and responsiveness of the immune system. All investigations have been aimed to evaluate selected, fragmentary reaction of the system and/or functional response of immunocompetent cells in RF/MW-exposed subjects. However, at the present state of knowledge it is not possible to conclude about the possible immunotropic potencies of RF/MW radiation. The undisturbed defensive, tolerogenic, and proregenerative activities of the immune system are commonly recognised as one of the most important homeostatic functions of the organism. Thus, basic immunoregulatory activities which can be observed and precisely quantified in microcultures of immune cells separated from the human blood, represent a unique and objective model for the investigation of possible immunotropic effects of electromagnetic fields (EMFs). To determine the potential immunomodulatory influences of EMFs, the immunotropic effects of pulse modulated microwave (1300 MHz) were investigated in the cultures of blood mononuclear cells from sixteen healthy donors

  5. Potency and selectivity of carprofen enantiomers for inhibition of bovine cyclooxygenase in whole blood assays.

    Science.gov (United States)

    Brentnall, Claire; Cheng, Zhangrui; McKellar, Quintin A; Lees, Peter

    2012-12-01

    Whole blood in vitro assays were used to determine the potency and selectivity of carprofen enantiomers for inhibition of the isoforms of cyclooxygenase (COX), COX-1 and COX-2, in the calf. S(+)-carprofen possessed preferential activity for COX-2 inhibition but, because the slopes of inhibition curves differed, the COX-1:COX-2 inhibition ratio decreased from 9.04:1 for inhibitory concentration (IC)10 to 1.84:1 for IC95. R(-) carprofen inhibited COX-2 preferentially only for low inhibition of the COX isoforms (IC10 COX-1:COX-2=6.63:1), whereas inhibition was preferential for COX-1 for a high level of inhibition (IC95 COX-1:COX-2=0.20:1). S(+) carprofen was the more potent inhibitor of COX isoforms; potency ratios S(+):R(-) carprofen were 11.6:1 for IC10 and 218:1 for IC90. Based on serum concentrations of carprofen enantiomers obtained after administration of a therapeutic dose of 1.4 mg/kg to calves subcutaneously, S(+)-carprofen concentrations exceeded the in vitro IC80 COX-2 value for 32 h and the IC20 for COX-1 for 33 h. The findings are discussed in relation to efficacy and safety of carprofen in calves. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. In vitro vaccine potency testing: a proposal for reducing animal use for requalification testing.

    Science.gov (United States)

    Brown, K; Stokes, W

    2012-01-01

    This paper proposes a program under which the use of animals for requalification of in vitro potency tests could be eliminated. Standard References (USDA/CVB nomenclature) would be developed, characterized, stored and monitored by selected reference laboratories worldwide. These laboratories would employ scientists skilled in protein and glycoprotein chemistry and equipped with state-of-the-art instruments for required analyses. After Standard References are established, the reference laboratories would provide them to the animal health industry as "gold standards". Companies would then establish and validate a correlation between the Standard Reference and the company Master Reference (USDA/CVB nomenclature) using an internal in vitro assay. After this correlation is established, the company could use the Standard References for qualifying, monitoring and requalifying company Master References without the use of animals. Such a program would eliminate the need for animals for requalification of Master References and the need for each company to develop and validate a battery of Master Reference Monitoring assays. It would also provide advantages in terms of reduced costs and reduced time for requalification testing. As such it would provide a strong incentive for companies to develop and use in vitro assays for potency testing.

  7. Bridging the Gap Between Validation and Implementation of Non-Animal Veterinary Vaccine Potency Testing Methods.

    Science.gov (United States)

    Dozier, Samantha; Brown, Jeffrey; Currie, Alistair

    2011-11-29

    In recent years, technologically advanced high-throughput techniques have been developed that replace, reduce or refine animal use in vaccine quality control tests. Following validation, these tests are slowly being accepted for use by international regulatory authorities. Because regulatory acceptance itself has not guaranteed that approved humane methods are adopted by manufacturers, various organizations have sought to foster the preferential use of validated non-animal methods by interfacing with industry and regulatory authorities. After noticing this gap between regulation and uptake by industry, we began developing a paradigm that seeks to narrow the gap and quicken implementation of new replacement, refinement or reduction guidance. A systematic analysis of our experience in promoting the transparent implementation of validated non-animal vaccine potency assays has led to the refinement of our paradigmatic process, presented here, by which interested parties can assess the local regulatory acceptance of methods that reduce animal use and integrate them into quality control testing protocols, or ensure the elimination of peripheral barriers to their use, particularly for potency and other tests carried out on production batches.

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

    Science.gov (United States)

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

    2017-09-01

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

  9. Titer on chip: new analytical tool for influenza vaccine potency determination.

    Directory of Open Access Journals (Sweden)

    Laura R Kuck

    Full Text Available Titer on Chip (Flu-ToC is a new technique for quantification of influenza hemagglutinin (HA concentration. In order to evaluate the potential of this new technique, a comparison of Flu-ToC to more conventional methods was conducted using recombinant HA produced in a baculovirus expression system as a test case. Samples from current vaccine strains were collected from four different steps in the manufacturing process. A total of 19 samples were analysed by Flu-ToC (blinded, single radial immunodiffusion (SRID, an enzyme-linked immunosorbent assay (ELISA, and the purity adjusted bicinchoninic acid assay (paBCA. The results indicated reasonable linear correlation between Flu-ToC and SRID, ELISA, and paBCA, with regression slopes of log-log plots being 0.91, 1.03, and 0.91, respectively. The average ratio for HA content measured by Flu-ToC relative to SRID, ELISA, and paBCA was 83%, 147%, and 81%, respectively; indicating nearly equivalent potency determination for Flu-ToC relative to SRID and paBCA. These results, combined with demonstrated multiplexed analysis of all components within a quadrivalent formulation and robust response to HA strains over a wide time period, support the conclusion that Flu-ToC can be used as a reliable and time-saving alternative potency assay for influenza vaccines.

  10. Conformational Flexibility Determines Selectivity and Antibacterial, Antiplasmodial, and Anticancer Potency of Cationic α-Helical Peptides*

    Science.gov (United States)

    Vermeer, Louic S.; Lan, Yun; Abbate, Vincenzo; Ruh, Emrah; Bui, Tam T.; Wilkinson, Louise J.; Kanno, Tokuwa; Jumagulova, Elmira; Kozlowska, Justyna; Patel, Jayneil; McIntyre, Caitlin A.; Yam, W. C.; Siu, Gilman; Atkinson, R. Andrew; Lam, Jenny K. W.; Bansal, Sukhvinder S.; Drake, Alex F.; Mitchell, Graham H.; Mason, A. James

    2012-01-01

    We used a combination of fluorescence, circular dichroism (CD), and NMR spectroscopies in conjunction with size exclusion chromatography to help rationalize the relative antibacterial, antiplasmodial, and cytotoxic activities of a series of proline-free and proline-containing model antimicrobial peptides (AMPs) in terms of their structural properties. When compared with proline-free analogs, proline-containing peptides had greater activity against Gram-negative bacteria, two mammalian cancer cell lines, and intraerythrocytic Plasmodium falciparum, which they were capable of killing without causing hemolysis. In contrast, incorporation of proline did not have a consistent effect on peptide activity against Mycobacterium tuberculosis. In membrane-mimicking environments, structures with high α-helix content were adopted by both proline-free and proline-containing peptides. In solution, AMPs generally adopted disordered structures unless their sequences comprised more hydrophobic amino acids or until coordinating phosphate ions were added. Proline-containing peptides resisted ordering induced by either method. The roles of the angle subtended by positively charged amino acids and the positioning of the proline residues were also investigated. Careful positioning of proline residues in AMP sequences is required to enable the peptide to resist ordering and maintain optimal antibacterial activity, whereas varying the angle subtended by positively charged amino acids can attenuate hemolytic potential albeit with a modest reduction in potency. Maintaining conformational flexibility improves AMP potency and selectivity toward bacterial, plasmodial, and cancerous cells while enabling the targeting of intracellular pathogens. PMID:22869378

  11. The murine local lymph node assay: Regulatory and potency considerations under REACH

    International Nuclear Information System (INIS)

    McGarry, Helen F.

    2007-01-01

    From June 2007, new chemicals legislation on the registration, evaluation, authorisation and restriction of chemicals (REACH) will come into force across the European Union. This will require the submission of data on human health effects of chemicals, including chemical safety assessments which will require measurements of potency. For skin sensitization hazard identification, REACH states that the first-choice in vivo assay is the local lymph node assay (LLNA). This test has also been the UK competent authority's preferred test for skin sensitization since 2002, and has now replaced guinea pig tests in dossiers submitted to it under the Notification of New Substances Regulations. Advantages of the LLNA over guinea pig tests include improvements in animal welfare, a more scientific approach to hazard identification, and the inclusion of a dose-response element in the endpoint, which enables an estimation of potency. However, notifiers to the UK competent authority have sometimes been reluctant to use the assay because of concerns over false-positive reactions. Across Europe, these concerns have been heightened in the lead-up to the introduction of REACH, since the use of in vivo alternatives to the LLNA will require scientific justification. This review will address some of these concerns from a regulatory perspective

  12. The murine local lymph node assay: regulatory and potency considerations under REACH.

    Science.gov (United States)

    McGarry, Helen F

    2007-09-05

    From June 2007, new chemicals legislation on the registration, evaluation, authorization and restriction of chemicals (REACH) will come into force across the European Union. This will require the submission of data on human health effects of chemicals, including chemical safety assessments which will require measurements of potency. For skin sensitization hazard identification, REACH states that the first-choice in vivo assay is the local lymph node assay (LLNA). This test has also been the UK competent authority's preferred test for skin sensitization since 2002, and has now replaced guinea pig tests in dossiers submitted to it under the Notification of New Substances Regulations. Advantages of the LLNA over guinea pig tests include improvements in animal welfare, a more scientific approach to hazard identification, and the inclusion of a dose-response element in the endpoint, which enables an estimation of potency. However, notifiers to the UK competent authority have sometimes been reluctant to use the assay because of concerns over false-positive reactions. Across Europe, these concerns have been heightened in the lead-up to the introduction of REACH, since the use of in vivo alternatives to the LLNA will require scientific justification. This review will address some of these concerns from a regulatory perspective.

  13. Potency of Agroindustrial Wastewaters to Increase the Dissolution of Phosphate Rock Fertilizers

    Directory of Open Access Journals (Sweden)

    Ainin Niswati

    2014-06-01

    Full Text Available The used of agroindustrial wastewaters are not maximum yet in Lampung Province, althought it can be used as an acid solvent because of its acidic properties. This study was aimed to explore the most potential agroindustrial wastewaters in dissolving phosphate rock through acidulation in the laboratory scale. The experiment was arranged in a factorial. The first factor was origined of phosphate rock (Sukabumi, west Java and Selagailingga, central Lampung and the second factor was solvent types (agroindustrial wastewaters which were pineapple, tapioca, tofu industry, and palm oil as well as conventional acid solvents which were HCl, H2SO4, and CH3COOH. The incubation processes were 0, 1, 2, and 3 months. The results showed that agroindustrial wastewaters that have the highest potency to solubize phosphate rock was industrial tofu wastewaters and followed by industrial wastewaters of tapioca, palm oil, and pineapple. Both the conventional acid and agroindustrial wastewaters solvent had a big potency to solubilize phosphate rock, however, its highest soluble P-value did not match with the ISO criteria for phosphate fertilizers Quality I (SNI because it did not reach the solubility of 80% of its total P2O5, but it has been qualified as a fertilizer both the quality phosphate A, B, and C (SNI.

  14. The Nucleation Potency of In Situ-Formed Oxides in Liquid Iron

    Science.gov (United States)

    Xu, Mingqin; Wang, Lu; Lu, Wenquan; Zeng, Long; Nadendla, Hari-Babu; Wang, Yun; Li, Jun; Hu, Qiaodan; Xia, Mingxu; Li, Jianguo

    2018-03-01

    The nucleation potency of iron oxides was verified experimentally through nucleation undercooling of liquid iron using aerodynamic levitation technology for minimized container contaminations. Steady undercooling values were subsequently obtained from multiple melting and freezing thermal cycles, with the average undercooling values of 223 K ± 3 K and 75 K ± 6 K (223 °C ± 3 °C and 75 °C ± 6 °C) for FeO-contained liquid and Fe3O4-contained liquid, respectively. The statistical results showed a negligible difference in the sizes and numbers of particles between FeO and Fe3O4 particles, indicating that the nucleation potency difference is attributed to the nature of nucleants rather than particle size or numbers. Furthermore, high-resolution transmission electron microscopy analysis showed that the potential nucleation interfaces can be assumed as { 1 1 0}_{{δ {{-Fe}}}} //( 0 0\\bar{2})_{FeO} and { 1 1 2}_{{δ {{-Fe}}}} //(\\bar{2} 0 2 )_{{{Fe}3 {O}4 }} , based on the detected exposed crystal planes of the oxide particles. Both the interfaces have relatively large values of lattice misfit, consistent with the experimentally measured undercooling based on Turnbull's lattice matching theory.

  15. Mirtazapine has a therapeutic potency in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of Parkinson's disease.

    Science.gov (United States)

    Kadoguchi, Naoto; Okabe, Shinji; Yamamura, Yukio; Shono, Misaki; Fukano, Tatsuya; Tanabe, Akie; Yokoyama, Hironori; Kasahara, Jiro

    2014-06-25

    Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), shows multiple pharmacological actions such as inhibiting presynaptic α2 noradrenaline receptor (NAR) and selectively activating 5-hydroxytriptamine (5-HT) 1A receptor (5-HT1AR). Mirtazapine was also reported to increase dopamine release in the cortical neurons with 5-HT dependent manner. To examine whether mirtazapine has a therapeutic potency in Parkinson's disease (PD), we examined this compound in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice model of PD. Male C57BL/6 mice were subjected to MPTP treatment to establish a PD model. Mirtazapine was administered once a day for 3 days after MPTP treatment. MPTP-induced motor dysfunction, assessed by beam-walking and rota-rod tests, was significantly improved by administration of mirtazapine. Biochemical examinations by high performance liquid chromatography and western blot analysis suggested mirtazapine facilitated utilization of dopamine by increasing turnover and protein expression of transporters, without affecting on neurodegenerative process by MPTP. These therapeutic effects of mirtazapine were reduced by administration of WAY100635, an inhibitor for 5HT1AR, or of clonidine, a selective agonist for α2-NAR, or of prazosin, an inhibitor for α1-NAR, respectively. Our results showed mirtazapine had a therapeutic potency against PD in a mouse model. Because PD patients sometimes show depression together, it will be a useful drug for a future PD treatment.

  16. Mirtazapine has a therapeutic potency in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of Parkinson’s disease

    Science.gov (United States)

    2014-01-01

    Background Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), shows multiple pharmacological actions such as inhibiting presynaptic α2 noradrenaline receptor (NAR) and selectively activating 5-hydroxytriptamine (5-HT) 1A receptor (5-HT1AR). Mirtazapine was also reported to increase dopamine release in the cortical neurons with 5-HT dependent manner. To examine whether mirtazapine has a therapeutic potency in Parkinson’s disease (PD), we examined this compound in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice model of PD. Results Male C57BL/6 mice were subjected to MPTP treatment to establish a PD model. Mirtazapine was administered once a day for 3 days after MPTP treatment. MPTP-induced motor dysfunction, assessed by beam-walking and rota-rod tests, was significantly improved by administration of mirtazapine. Biochemical examinations by high performance liquid chromatography and western blot analysis suggested mirtazapine facilitated utilization of dopamine by increasing turnover and protein expression of transporters, without affecting on neurodegenerative process by MPTP. These therapeutic effects of mirtazapine were reduced by administration of WAY100635, an inhibitor for 5HT1AR, or of clonidine, a selective agonist for α2-NAR, or of prazosin, an inhibitor for α1-NAR, respectively. Conclusion Our results showed mirtazapine had a therapeutic potency against PD in a mouse model. Because PD patients sometimes show depression together, it will be a useful drug for a future PD treatment. PMID:24965042

  17. The lethality test used for estimating the potency of antivenoms against Bothrops asper snake venom: pathophysiological mechanisms, prophylactic analgesia, and a surrogate in vitro assay.

    Science.gov (United States)

    Chacón, Francisco; Oviedo, Andrea; Escalante, Teresa; Solano, Gabriela; Rucavado, Alexandra; Gutiérrez, José María

    2015-01-01

    The potency of antivenoms is assessed by analyzing the neutralization of venom-induced lethality, and is expressed as the Median Effective Dose (ED50). The present study was designed to investigate the pathophysiological mechanisms responsible for lethality induced by the venom of Bothrops asper, in the experimental conditions used for the evaluation of the neutralizing potency of antivenoms. Mice injected with 4 LD50s of venom by the intraperitoneal route died within ∼25 min with drastic alterations in the abdominal organs, characterized by hemorrhage, increment in plasma extravasation, and hemoconcentration, thus leading to hypovolemia and cardiovascular collapse. Snake venom metalloproteinases (SVMPs) play a predominat role in lethality, as judged by partial inhibition by the chelating agent CaNa2EDTA. When venom was mixed with antivenom, there was a venom/antivenom ratio at which hemorrhage was significantly reduced, but mice died at later time intervals with evident hemoconcentration, indicating that other components in addition to SVMPs also contribute to plasma extravasation and lethality. Pretreatment with the analgesic tramadol did not affect the outcome of the neutralization test, thus suggesting that prophylactic (precautionary) analgesia can be introduced in this assay. Neutralization of lethality in mice correlated with neutralization of in vitro coagulant activity in human plasma. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. (-)-Meptazinol-melatonin hybrids as novel dual inhibitors of cholinesterases and amyloid-β aggregation with high antioxidant potency for Alzheimer's therapy.

    Science.gov (United States)

    Cheng, Shaobing; Zheng, Wei; Gong, Ping; Zhou, Qiang; Xie, Qiong; Yu, Lining; Zhang, Peiyi; Chen, Liangkang; Li, Juan; Chen, Jianxing; Chen, Hailin; Chen, Hongzhuan

    2015-07-01

    The multifactorial pathogenesis of Alzheimer's disease (AD) implicates that multi-target-directed ligands (MTDLs) intervention may represent a promising therapy for AD. Amyloid-β (Aβ) aggregation and oxidative stress, two prominent neuropathological hallmarks in patients, play crucial roles in the neurotoxic cascade of this disease. In the present study, a series of novel (-)-meptazinol-melatonin hybrids were designed, synthesized and biologically characterized as potential MTDLs against AD. Among them, hybrids 7-7c displayed higher dual inhibitory potency toward cholinesterases (ChEs) and better oxygen radical absorbance capacity (ORAC) than the parental drugs. Furthermore, compound 7c could effectively inhibit Aβ self-aggregation, showed favorable safety and the blood-brain barrier (BBB) permeability. Therefore, 7c may serve as a valuable candidate that is worthy of further investigations in the treatment of AD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Potency of whole virus particle and split virion vaccines using dissolving microneedle against challenges of H1N1 and H5N1 influenza viruses in mice.

    Science.gov (United States)

    Nakatsukasa, Akihiro; Kuruma, Koji; Okamatsu, Masatoshi; Hiono, Takahiro; Suzuki, Mizuho; Matsuno, Keita; Kida, Hiroshi; Oyamada, Takayoshi; Sakoda, Yoshihiro

    2017-05-15

    Transdermal vaccination using a microneedle (MN) confers enhanced immunity compared with subcutaneous (SC) vaccination. Here we developed a novel dissolving MN patch for the influenza vaccine. The potencies of split virion and whole virus particle (WVP) vaccines prepared from A/Puerto Rico/8/1934 (H1N1) and A/duck/Hokkaido/Vac-3/2007 (H5N1), respectively, were evaluated. MN vaccination induced higher neutralizing antibody responses than SC vaccination in mice. Moreover, MN vaccination with a lower dose of antigens conferred protective immunity against lethal challenges of influenza viruses than SC vaccination in mice. These results suggest that the WVP vaccines administered using MN are an effective combination for influenza vaccine to be further validated in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. A Study of the potency of construction service industries to support the first nuclear power plant construction in Indonesia

    International Nuclear Information System (INIS)

    Dharu Dewi; Sriyana

    2008-01-01

    The study was conducted to identify the potency of construction service industries to participate in nuclear power plant program in Indonesia. The potency is identified by evaluation results of national industries potency in some multinational construction service industries. The research methodology chosen was the survey method by sending questionnaires, visits to National industries, interview, and literature study. The data collection technique was sampling purposive. Data can be obtained from both primary and secondary data. The study results showed that the performance of construction service industries to support the NPP program must be increased through the selection of competent human resources, reliable equipment and an effective and efficient project management system, so that they can be expected to play necessary role in the nuclear power plant construction in Indonesia. (author)

  1. Transformational leadership and group potency in small military units: The mediating role of group identification and cohesion

    Directory of Open Access Journals (Sweden)

    Carlos García-Guiu

    2016-12-01

    Full Text Available In the present study, we examined an exploratory model to assess the relationship between transformational leadership and group potency and analyze the mediating role of group identification and cohesion. The research was conducted with squads of the Spanish Army. The sample was composed of 243 members of 51 squads of operational units. Our findings highlighted the importance of the transformational leadership style of command of non-commissioned officers (NCOs due to its positive relationship with the group potency of the squad. We also analyzed the indirect relationships between transformational leadership and group identification and group cohesion and found that the latter variables played a mediating role between transformational leadership and group potency. The conclusions of this study are relevant due to the growing importance of transformational leadership and actions implemented at lower levels of the command chain for the success of missions of security organizations and defense.

  2. Practice insights on patient care-management overview for chemoradiation toxic mucositis-guidelines, guideline-supported therapies and high potency polymerized cross-linked sucralfate (ProThelial).

    Science.gov (United States)

    McCullough, Ricky W

    2018-01-01

    Aim To offer a practice insight for the management of chemoradiation toxic mucositis. Method Review chemoradiation toxic mucositis, its pathobiology and breadth of symptom presentation. Review mucositis guidelines and guideline-supported anti-mucositis therapies. Offer guidance on guidelines and an abbreviated review of high potency cross-linked sucralfate for management of chemoradiation toxic mucositis. Result There are six major mucositis guidelines but only one that is current and regularly updated. Guidelines from the Multinational Association Supportive Cancer Care suggest 14 interventions gleaned from controlled trials, 12 of which are off-label uses of therapies that offer statistically significant but incrementally beneficial outcomes. Several evidence-based limitations of guidelines are discussed. Data on high potency polymerized cross-linked sucralfate confirming complete prevention and rapid (2-3 days) elimination, sustained throughout cancer treatment is verified as high quality evidence in accordance to standards adopted by Agency for Healthcare Research and Quality. A 96-97% reduction in mucositis duration qualifies as a positive Glasziou treatment effect, which is discussed as an additional measure of evidence-based medicine. Conclusion Statistically significant but fractional treatment effects of guideline-supported interventions are not likely to substantially alter the course of mucositis when it occurs nor completely prevent its onset. Complete prevention and rapid sustained elimination should be the goal, therefore high potency polymerized cross-linked sucralfate may be useful. Where guidelines fail, institution-based protocols led by oncology pharmacists could succeed. In an effort to eliminate toxic mucositis, enhance compliance to chemoradiation regimens, and improve survival, such protocols for practice may verify pharmacoeconomic benefits, if any, in using high potency polymerized cross-linked sucralfate to manage toxic mucositis.

  3. Development of an in vitro potency assay for human skeletal muscle derived cells.

    Science.gov (United States)

    Thurner, Marco; Asim, Faheem; Garczarczyk-Asim, Dorota; Janke, Katrin; Deutsch, Martin; Margreiter, Eva; Troppmair, Jakob; Marksteiner, Rainer

    2018-01-01

    Potency is a quantitative measure of the desired biological function of an advanced therapy medicinal product (ATMP) and is a prerequisite for market approval application (MAA). To assess the potency of human skeletal muscle-derived cells (SMDCs), which are currently investigated in clinical trials for the regeneration of skeletal muscle defects, we evaluated acetylcholinesterase (AChE), which is expressed in skeletal muscle and nervous tissue of all mammals. CD56+ SMDCs were separated from CD56- SMDCs by magnetic activated cell sorting (MACS) and both differentiated in skeletal muscle differentiation medium. AChE activity of in vitro differentiated SMDCs was correlated with CD56 expression, fusion index, cell number, cell doubling numbers, differentiation markers and compared to the clinical efficacy in patients treated with SMDCs against fecal incontinence. CD56- SMDCs did not form multinucleated myotubes and remained low in AChE activity during differentiation. CD56+ SMDCs generated myotubes and increased in AChE activity during differentiation. AChE activity was found to accurately reflect the number of CD56+ SMDCs in culture, their fusion competence, and cell doubling number. In patients with fecal incontinence responding to SMDCs treatment, the improvement of clinical symptoms was positively linked with the AChE activity of the SMDCs injected. AChE activity was found to truly reflect the in vitro differentiation status of SMDCs and to be superior to the mere use of surface markers as it reflects not only the number of myogenic SMDCs in culture but also their fusion competence and population doubling number, thus combining cell quality and quantification of the expected mode of action (MoA) of SMDCs. Moreover, the successful in vitro validation of the assay proves its suitability for routine use. Most convincingly, our results demonstrate a link between clinical efficacy and the AChE activity of the SMDCs preparations used for the treatment of fecal

  4. The impact of vehicle on the relative potency of skin-sensitizing chemicals in the local lymph node assay.

    Science.gov (United States)

    Jowsey, Ian R; Clapp, Catherine J; Safford, Bob; Gibbons, Ben T; Basketter, David A

    2008-01-01

    The identification and characterization of chemicals that possess skin-sensitizing potential are typically performed using predictive tests. However, human exposure to skin-sensitizing chemicals often occurs via a matrix (vehicle) that differs from that used in these tests. It is thus important to account for the potential impact of vehicle differences when undertaking quantitative risk assessment for skin sensitization. This is achieved through the application of a specific sensitization assessment factor (SAF), scaled between 1 and 10, when identifying an acceptable exposure level. The objective of the analysis described herein is to determine the impact of vehicle differences on local lymph node assay (LLNA) EC3 values (concentrations of test chemical required to provoke a 3-fold increase in lymph node cell proliferation). Initially, the inherent variability of the LLNA was investigated by examining the reproducibility of EC3 values for 14 chemicals that have been tested more than once in the same vehicle (4:1 acetone:olive oil, AOO). This analysis reveals that the variability in EC3 value for these chemicals following multiple assessments is LLNA using at least 2 of 15 different vehicles. These data demonstrate that often the variability in EC3 values observed for a given chemical in different vehicles is no greater than the 5-fold inherent variability observed when assessing a chemical in the same vehicle on multiple occasions. However, there are examples where EC3 values for a chemical differ by a factor of more than 10 between different vehicles. These observations were often associated with an apparent underestimation of potency (higher EC3 values) with predominantly aqueous vehicles or propylene glycol. These data underscore the need to consider vehicle effects in the context of skin-sensitization risk assessments.

  5. Comparative potency approach based on H2AX assay for estimating the genotoxicity of polycyclic aromatic hydrocarbons.

    Science.gov (United States)

    Audebert, M; Zeman, F; Beaudoin, R; Péry, A; Cravedi, J-P

    2012-04-01

    Polycyclic Aromatic Hydrocarbons (PAHs) constitute a family of over one hundred compounds and can generally be found in complex mixtures. PAHs metabolites cause DNA damage which can lead to the development of carcinogenesis. Toxicity assessment of PAH complex mixtures is currently expressed in terms of toxic equivalents, based on Toxicity Equivalent Factors (TEFs). However, the definition of new TEFs for a large number of PAH could overcome some limitations of the current method and improve cancer risk assessment. The current investigation aimed at deriving the relative potency factors of PAHs, based on their genotoxic effect measured in vitro and analyzed with mathematical models. For this purpose, we used a new genotoxic assay (γH2AX) with two human cell lines (HepG2 and LS-174T) to analyze the genotoxic properties of 13 selected PAHs at low doses after 24h treatment. The dose-response for genotoxic effects was modeled with a Hill model; equivalency between PAHs at low dose was assessed by applying constraints to the model parameters. In the two cell lines tested, we observed a clear dose-response for genotoxic effects for 11 tested compounds. LS-174T was on average ten times more sensitive than HepG2 towards PAHs regarding genotoxicity. We developed new TEFs, which we named Genotoxic Equivalent Factor (GEF). Calculated GEF for the tested PAHs were generally higher than the TEF usually used. Our study proposed a new in vitro based method for the establishment of relevant TEFs for PAHs to improve cancer risk assessment. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Evaluation of the skin sensitizing potency of chemicals by using the existing methods and considerations of relevance for elicitation

    DEFF Research Database (Denmark)

    Basketter, David A; Andersen, Klaus E; Liden, Carola

    2005-01-01

    be translated into practical thresholds and whether these could be set for both induction and elicitation. Examples are given for substances falling into various potency groups for skin sensitization relating to results from the local lymph node assay, the guinea pig maximization test, the Buehler method...... products, cosmetics, food and feeding stuffs, which are subject to specific community legislation. The main questions that are answered in this report are whether it would be possible to give detailed guidance on how to grade allergen potency based on the existing methods, whether such grading could...

  7. Human Long Noncoding RNA Regulation of Stem Cell Potency and Differentiation

    Directory of Open Access Journals (Sweden)

    Seahyoung Lee

    2017-01-01

    Full Text Available Because of their capability of differentiation into lineage-specific cells, stem cells are an attractive therapeutic modality in regenerative medicine. To develop an effective stem cell-based therapeutic strategy with predictable results, deeper understanding of the underlying molecular mechanisms of stem cell differentiation and/or pluripotency maintenance is required. Thus, reviewing the key factors involved in the transcriptional and epigenetic regulation of stem cell differentiation and maintenance is important. Accumulating data indicate that long noncoding RNAs (lncRNAs mediate numerous biological processes, including stem cell differentiation and maintenance. Here, we review recent findings on the human lncRNA regulation of stem cell potency and differentiation. Although the clinical implication of these lncRNAs is only beginning to be elucidated, it is anticipated that lncRNAs will become important therapeutic targets in the near future.

  8. Non-cannabinoid constituents from a high potency Cannabis sativa variety

    Science.gov (United States)

    Radwan, Mohamed M.; ElSohly, Mahmoud A.; Slade, Desmond; Ahmed, Safwat A.; Wilson, Lisa; El-Alfy, Abir T.; Khan, Ikhlas A.; Ross, Samir A.

    2016-01-01

    Six new non-cannabinoid constituents were isolated from a high potency Cannabis sativa L. variety, namely 5-acetoxy-6-geranyl-3-n-pentyl-1,4-benzoquinone (1), 4,5-dihydroxy-2,3,6-trimethoxy-9,10-dihydrophenanthrene (2), 4-hydroxy-2,3,6,7-tetramethoxy-9,10-dihydrophenanthrene (3), 4,7-dimethoxy-1,2,5-trihydroxyphenanthrene (4), cannflavin C (5) and β-sitosteryl-3-O-β-D-glucopyranoside-2'-O-palmitate (6). In addition, five known compounds, α-cannabispiranol (7), chrysoeriol (8), 6-prenylapigenin (9), cannflavin A (10) and β-acetyl cannabispiranol (11) were identified, with 8 and 9 being reported for the first time from cannabis. Some isolates displayed weak to strong antimicrobial, antileishmanial, antimalarial and anti-oxidant activities. Compounds 2–4 were inactive as analgesics. PMID:18774146

  9. Assessment of the estrogenic potency of effluents from petrochemical facilities and a petroleum refinery in Ontario

    International Nuclear Information System (INIS)

    Sherry, J.P.; Trepanier, T.; Tinson, C.; Munro, S.

    2002-01-01

    Studies have shown that wastewater from refineries could induce vitellogenin (Vg) in juvenile rainbow trout. Vg is a biomarker of exposure to estrogenic chemicals. This study reassessed the estrogenic potency of the wastewater from an Ontario refinery and assessed the estrogenicity of wastewater from 3 petrochemical facilities. A 21 day static renewal test was conducted to test the effluents and in which a competitive binding ELISA detected induced Vg. Statistical testing for tank effects was performed in a replicated tank design and the St. Clair River water from upstream industrial facilities was used as a negative reference. The positive control treatment was waterborne 17β-estradiol. Wastewater from the petroleum refinery induced Vg in the treated fish, but wastewater from the petrochemical effluents did not induce detectable levels of Vg in treated trout. The information obtained through this study will be used to determine the potential for responses in feral fish

  10. New analogs of the CART peptide with anorexigenic potency: the importance of individual disulfide bridges.

    Science.gov (United States)

    Blechová, Miroslava; Nagelová, Veronika; Záková, Lenka; Demianová, Zuzana; Zelezná, Blanka; Maletínská, Lenka

    2013-01-01

    The CART (cocaine- and amphetamine-regulated transcript) peptide is an anorexigenic neuropeptide that acts in the hypothalamus. The receptor and the mechanism of action of this peptide are still unknown. In our previous study, we showed that the CART peptide binds specifically to PC12 rat pheochromocytoma cells in both the native and differentiated into neuronal phenotype. Two biologically active forms, CART(55-102) and CART(61-102), with equal biological activity, contain three disulfide bridges. To clarify the importance of each of these disulfide bridges in maintaining the biological activity of CART(61-102), an Ala scan at particular S-S bridges forming cysteines was performed, and analogs with only one or two disulfide bridges were synthesized. In this study, a stabilized CART(61-102) analog with norleucine instead of methionine at position 67 was also prepared and was found to bind to PC12 cells with an anorexigenic potency similar to that of CART(61-102). The binding study revealed that out of all analogs tested, [Ala(68,86)]CART(61-102), which contains two disulfide bridges (positions 74-94 and 88-101), preserved a high affinity to both native PC12 cells and those that had been differentiated into neurons. In food intake and behavioral tests with mice after intracerebroventricular administration, this analog showed strong and long-lasting anorexigenic potency. Therefore, the disulfide bridge between cysteines 68 and 86 in CART(61-102) can be omitted without a loss of biological activity, but the preservation of two other disulfide bridges and the full-length peptide are essential for biological activity. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Elucidating the structural basis for differing enzyme inhibitor potency by cryo-EM.

    Science.gov (United States)

    Rawson, Shaun; Bisson, Claudine; Hurdiss, Daniel L; Fazal, Asif; McPhillie, Martin J; Sedelnikova, Svetlana E; Baker, Patrick J; Rice, David W; Muench, Stephen P

    2018-02-20

    Histidine biosynthesis is an essential process in plants and microorganisms, making it an attractive target for the development of herbicides and antibacterial agents. Imidazoleglycerol-phosphate dehydratase (IGPD), a key enzyme within this pathway, has been biochemically characterized in both Saccharomyces cerevisiae ( Sc_ IGPD) and Arabidopsis thaliana ( At_ IGPD). The plant enzyme, having been the focus of in-depth structural analysis as part of an inhibitor development program, has revealed details about the reaction mechanism of IGPD, whereas the yeast enzyme has proven intractable to crystallography studies. The structure-activity relationship of potent triazole-phosphonate inhibitors of IGPD has been determined in both homologs, revealing that the lead inhibitor (C348) is an order of magnitude more potent against Sc_ IGPD than At_ IGPD; however, the molecular basis of this difference has not been established. Here we have used single-particle electron microscopy (EM) to study structural differences between the At and Sc_ IGPD homologs, which could influence the difference in inhibitor potency. The resulting EM maps at ∼3 Å are sufficient to de novo build the protein structure and identify the inhibitor binding site, which has been validated against the crystal structure of the At_ IGPD/C348 complex. The structure of Sc _IGPD reveals that a 24-amino acid insertion forms an extended loop region on the enzyme surface that lies adjacent to the active site, forming interactions with the substrate/inhibitor binding loop that may influence inhibitor potency. Overall, this study provides insights into the IGPD family and demonstrates the power of using an EM approach to study inhibitor binding. Copyright © 2018 the Author(s). Published by PNAS.

  12. Enhanced neutralization potency of botulinum neurotoxin antibodies using a red blood cell-targeting fusion protein.

    Directory of Open Access Journals (Sweden)

    Sharad P Adekar

    2011-03-01

    Full Text Available Botulinum neurotoxin (BoNT potently inhibits cholinergic signaling at the neuromuscular junction. The ideal countermeasures for BoNT exposure are monoclonal antibodies or BoNT antisera, which form BoNT-containing immune complexes that are rapidly cleared from the general circulation. Clearance of opsonized toxins may involve complement receptor-mediated immunoadherence to red blood cells (RBC in primates or to platelets in rodents. Methods of enhancing immunoadherence of BoNT-specific antibodies may increase their potency in vivo. We designed a novel fusion protein (FP to link biotinylated molecules to glycophorin A (GPA on the RBC surface. The FP consists of an scFv specific for murine GPA fused to streptavidin. FP:mAb:BoNT complexes bound specifically to the RBC surface in vitro. In a mouse model of BoNT neutralization, the FP increased the potency of single and double antibody combinations in BoNT neutralization. A combination of two antibodies with the FP gave complete neutralization of 5,000 LD50 BoNT in mice. Neutralization in vivo was dependent on biotinylation of both antibodies and correlated with a reduction of plasma BoNT levels. In a post-exposure model of intoxication, FP:mAb complexes gave complete protection from a lethal BoNT/A1 dose when administered within 2 hours of toxin exposure. In a pre-exposure prophylaxis model, mice were fully protected for 72 hours following administration of the FP:mAb complex. These results demonstrate that RBC-targeted immunoadherence through the FP is a potent enhancer of BoNT neutralization by antibodies in vivo.

  13. Enhancing potency of siRNA targeting fusion genes by optimization outside of target sequence.

    Science.gov (United States)

    Gavrilov, Kseniya; Seo, Young-Eun; Tietjen, Gregory T; Cui, Jiajia; Cheng, Christopher J; Saltzman, W Mark

    2015-12-01

    Canonical siRNA design algorithms have become remarkably effective at predicting favorable binding regions within a target mRNA, but in some cases (e.g., a fusion junction site) region choice is restricted. In these instances, alternative approaches are necessary to obtain a highly potent silencing molecule. Here we focus on strategies for rational optimization of two siRNAs that target the junction sites of fusion oncogenes BCR-ABL and TMPRSS2-ERG. We demonstrate that modifying the termini of these siRNAs with a terminal G-U wobble pair or a carefully selected pair of terminal asymmetry-enhancing mismatches can result in an increase in potency at low doses. Importantly, we observed that improvements in silencing at the mRNA level do not necessarily translate to reductions in protein level and/or cell death. Decline in protein level is also heavily influenced by targeted protein half-life, and delivery vehicle toxicity can confound measures of cell death due to silencing. Therefore, for BCR-ABL, which has a long protein half-life that is difficult to overcome using siRNA, we also developed a nontoxic transfection vector: poly(lactic-coglycolic acid) nanoparticles that release siRNA over many days. We show that this system can achieve effective killing of leukemic cells. These findings provide insights into the implications of siRNA sequence for potency and suggest strategies for the design of more effective therapeutic siRNA molecules. Furthermore, this work points to the importance of integrating studies of siRNA design and delivery, while heeding and addressing potential limitations such as restricted targetable mRNA regions, long protein half-lives, and nonspecific toxicities.

  14. Development and Rainfed Paddy Soils Potency Derived from Lacustrine Material in Paguyaman, Gorontalo

    Directory of Open Access Journals (Sweden)

    Nurdin

    2011-09-01

    Full Text Available Rainfed paddy soils that are derived from lacustrine and include of E4 agroclimatic zone have many unique properties and potentially for paddy and corn plantations. This sreseach was aimed to: (1 study the soil development of rainfed paddy soils derived from lacustrine and (2 evaluate rainfed paddy soils potency for paddy and corn in Paguyaman. Soil samples were taken from three profiles according to toposequent, and they were analyzed in laboratory. Data were analyzed with descriptive-quantitative analysis. Furthermore, assessment on rainfed paddy soils potency was conducted with land suitability analysis using parametric approach. Results indicate that all pedon had evolved with B horizons structurization. However, pedon located on the summit slope was more developed and intensely weathered than those of the shoulder and foot slopes.The main pedogenesis in all pedons were through elluviation, illuviation, lessivage, pedoturbation, and gleization processes. The main factors of pedogenesis were climate, age (time and topography factors. Therefore, P1 pedons are classified as Ustic Endoaquerts, fine, smectitic, isohypertermic; P2 as Vertic Endoaquepts, fine, smectitic, isohypertermic; and P3 as Vertic Epiaquepts, fine, smectitic, isohypertermic. Based on the potentials of the land, the highest of land suitability class (LSC of land utilization type (LUT local paddy was highly suitable (S1, while the lowest one was not suitable with nutrient availability as the limiting factor (Nna. The highest LCS of paddy-corn LUT was marginally suitable with water availability as the limiting factor (S3wa, while the lower LSC was not suitable with nutrient availabily as the limiting factor (Nna.

  15. Seminal vesicle sparing laparoscopic radical prostatectomy using a low-energy source: Better continence and potency

    Directory of Open Access Journals (Sweden)

    Shrenik J Shah

    2009-01-01

    Full Text Available Objectives: Ongoing with the newer developments in laparoscopic radical prostatectomy (LRP, we report our experience in a consecutive series of 42 patients with a mean 18-month follow-up. We also studied the use of a low-energy source, especially in the region of the prostatic apex and the neurovascular bundle and evaluated its outcome on continence and potency. Materials and Methods: Between November 2003 and December 2008, 50 patients aged 50-80 yrs underwent LRP with vesicourethral anastomosis and of these, 42 patients who had a minimum follow-up of 3 months were selected for the study. Of these, the initial 16 patients were operated by the routine method and the 26 patients operated in the later part of our experience were operated upon using a minimal energy source. Results: The mean follow-up was 18 months (range 3-60. Continence was evaluated at 1, 3, 6, and 12 months. Eleven of the 16 patients in Group I were continent as compared with 21 of 26 patients in Group II. The difference in continence rates was mainly due to less use of electrocautery and harmonic scalpel at the bladder neck. Of the eight patients who were potent pre-operatively in Group I, four remained potent 3 months after LRP. In Group II, 20 of the 26 patients were potent pre-operatively and 16 remained potent 3 months after LRP. Conclusions: Use of a low-energy source at the bladder neck and neurovascular bundle, sparing of seminal vesicle, and leaving behind a long, healthy stump of the urethra during apical dissection, is associated with better continence and potency without compromising oncological outcome.

  16. Petroleum distillates suppress in vitro metabolic activation: higher [S-9] required in the Salmonella/microsome mutagenicity assay.

    Science.gov (United States)

    Carver, J H; Machado, M L; MacGregor, J A

    1985-01-01

    To determine if standard conditions used in the Salmonella/mammalian microsome mutagenicity assay could reliably screen complex petroleum samples, two high-boiling (700-1,070 degrees F) distillates and their separated aromatic fractions were tested. The initial mutagenic activities were inconsistent with the samples' known polyaromatic hydrocarbon (PAH) contents and observed potencies in a dermal carcinogenesis bioassay. A significant mutagenic response was observed only at S-9 concentrations 5 to 10 times higher than those used in the standard assay, supporting the use of elevated levels of S-9 in the Salmonella/microsome assay to assess the carcinogenic potential of petroleum-derived materials. All four samples masked the expected mutagenic activity of added PAHs (benzo[a]pyrene and perylene). Data suggested that petroleum distillates suppress the functional efficacy of the S-9; possible mechanisms are discussed.

  17. Relative embryotoxic potency of p-substituted phenols in the embryonic stem cell test (EST) and comparison to their toxic potency in vivo and in the whole embryo culture (WEC) assay

    NARCIS (Netherlands)

    Strikwold, M.; Woutersen, R.A.; Spenkelink, B.; Punt, A.; Rietjens, I.M.C.M.

    2012-01-01

    The applicability of the embryonic stem cell test (EST) as an alternative for in vivo embryotoxicity testing was evaluated for a series of five p-substituted phenols. To this purpose, the potency ranking for this class of compounds derived from the inhibition of cardiomyocyte differentiation in the

  18. INTERNATIONALIZATION IN HIGHER EDUCATION

    Directory of Open Access Journals (Sweden)

    Catalina Crisan-Mitra

    2016-03-01

    Full Text Available Internationalization of higher education is one of the key trends of development. There are several approaches on how to achieve competitiveness and performance in higher education and international academic mobility; students’ exchange programs, partnerships are some of the aspects that can play a significant role in this process. This paper wants to point out the student’s perception regarding two main directions: one about the master students’ expectation regarding how an internationalized master should be organized and should function, and second the degree of satisfaction of the beneficiaries of internationalized master programs from Babe-Bolyai University. This article is based on an empirical qualitative research that was implemented to students of an internationalized master from the Faculty of Economics and Business Administration. This research can be considered a useful example for those preoccupied to increase the quality of higher education and conclusions drawn have relevance both theoretically and especially practically.

  19. Detecting Novelty and Significance

    Science.gov (United States)

    Ferrari, Vera; Bradley, Margaret M.; Codispoti, Maurizio; Lang, Peter J.

    2013-01-01

    Studies of cognition often use an “oddball” paradigm to study effects of stimulus novelty and significance on information processing. However, an oddball tends to be perceptually more novel than the standard, repeated stimulus as well as more relevant to the ongoing task, making it difficult to disentangle effects due to perceptual novelty and stimulus significance. In the current study, effects of perceptual novelty and significance on ERPs were assessed in a passive viewing context by presenting repeated and novel pictures (natural scenes) that either signaled significant information regarding the current context or not. A fronto-central N2 component was primarily affected by perceptual novelty, whereas a centro-parietal P3 component was modulated by both stimulus significance and novelty. The data support an interpretation that the N2 reflects perceptual fluency and is attenuated when a current stimulus matches an active memory representation and that the amplitude of the P3 reflects stimulus meaning and significance. PMID:19400680

  20. Significant NRC Enforcement Actions

    Data.gov (United States)

    Nuclear Regulatory Commission — This dataset provides a list of Nuclear Regulartory Commission (NRC) issued significant enforcement actions. These actions, referred to as "escalated", are issued by...

  1. Establishment of an animal challenge model as a potency assay for an inactivated Enterovirus Type 71 vaccine.

    Science.gov (United States)

    Wang, Kun-Teng; Lin, Shih-Jie; Wang, Hsiu-Chi; Chen, Pin-Chun; Lin, Jiao-Jung; Chiang, Jen-Ron; Chang, Chao-Liang; Shih, Daniel Yang-Chih; Lo, Chi-Fang; Wang, Der-Yuan

    2016-07-01

    Enterovirus 71 (EV71) belongs to the Enterovirus genus of the Picornaviridae family, and its occurrence in Asia is associated with hand-foot-and-mouth disease (HFMD), leading to death in some cases, in young children. An effective EV71 vaccine is therefore urgently needed. In this study, we established a two-step EV71 vaccine potency model. Intraperitoneal injections in 2-day-old suckling mice were used to establish the LD50 of EV71 B4, B5, C2, C4, and C5 subgenotypes. Only C4 caused hind limb paralysis in mice (LD50: 2.62 ± 0.45). EV71 VP1 protein was identified in the brain tissues at histology. In the second phase of the model, 3-week-old female ICR mice received one primary and two boosting i.p. injections of formalin-inactivated EV71 B4 and C4 vaccine. Immunized serum was neutralized in vitro with EV71 C4 and applied to the murine challenge model. The C4 vaccine-immunized serum exhibited the highest protective titre (ED50 = 114.6), while the B4 immunized serum had the weakest protective titre (ED50 = 34.3). Additionally, human plasma and intravenous immunoglobulin displayed significant protection in the neutralization assay. Our results could facilitate candidate EV71 vaccine immunogenicity and efficacy evaluations, and may help establish reference EV71 antisera in the future. Copyright © 2016 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  2. Tablet potency of Tianeptine in coated tablets by near infrared spectroscopy: model optimisation, calibration transfer and confidence intervals.

    Science.gov (United States)

    Boiret, Mathieu; Meunier, Loïc; Ginot, Yves-Michel

    2011-02-20

    A near infrared (NIR) method was developed for determination of tablet potency of active pharmaceutical ingredient (API) in a complex coated tablet matrix. The calibration set contained samples from laboratory and production scale batches. The reference values were obtained by high performance liquid chromatography (HPLC) and partial least squares (PLS) regression was used to establish a model. The model was challenged by calculating tablet potency of two external test sets. Root mean square errors of prediction were respectively equal to 2.0% and 2.7%. To use this model with a second spectrometer from the production field, a calibration transfer method called piecewise direct standardisation (PDS) was used. After the transfer, the root mean square error of prediction of the first test set was 2.4% compared to 4.0% without transferring the spectra. A statistical technique using bootstrap of PLS residuals was used to estimate confidence intervals of tablet potency calculations. This method requires an optimised PLS model, selection of the bootstrap number and determination of the risk. In the case of a chemical analysis, the tablet potency value will be included within the confidence interval calculated by the bootstrap method. An easy to use graphical interface was developed to easily determine if the predictions, surrounded by minimum and maximum values, are within the specifications defined by the regulatory organisation. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. Expansion of the in vitro assay for Leptospira potency testing to other Serovars: Case study with Leptospira hardjo

    Science.gov (United States)

    The Code for Federal Regulations (9 CFR 113:101-104) specifies how vaccine potency is evaluated in a hamster model for evaluation of leptospiral vaccines against pomona, icterohaemorrhagiae, canicola, and grippotyphosa serotypes of Leptospira interrogans. There are several issues which complicate th...

  4. Conjugation of a cell-penetrating peptide to parathyroid hormone affects its structure, potency, and transepithelial permeation

    DEFF Research Database (Denmark)

    Kristensen, Mie; de Groot, Anne Marit; Berthelsen, Jens

    2015-01-01

    hormone, i.e. PTH(1-34), and to evaluate the effect with regards to secondary structure, potency in Saos-2 cells, immunogenicity, safety as well as the transepithelial permeation across monolayers by using the Caco-2 cell culture model. Further, co-administration of CPP and PTH(1-34) as an alternative...

  5. Evaluation and validation of a single-dilution potency assay based upon serology of vaccines containing diphtheria toxoid: statistical analysis

    NARCIS (Netherlands)

    Marsman FR; Akkermans AM; Hendriksen CFM; de Jong WH

    1993-01-01

    This document presents the results of a validation study to the use of a single dilution assay in potency testing of the diphtheria component of DPT-polio vaccines. Based on historical data of multi-dilution assays on 27 consecutive batches a simulation study was performed to test the actual

  6. A novel variable antibody fragment dimerized by leucine zippers with enhanced neutralizing potency against rabies virus G protein compared to its corresponding single-chain variable antibody fragment.

    Science.gov (United States)

    Li, Zhuang; Cheng, Yue; Xi, Hualong; Gu, Tiejun; Yuan, Ruosen; Chen, Xiaoxu; Jiang, Chunlai; Kong, Wei; Wu, Yongge

    2015-12-01

    Fatal rabies can be prevented effectively by post-exposure prophylactic (PEP) with rabies immunoglobulin (RIG). Single-chain variable fragments (scFv), which are composed of a variable heavy chain (VH) and a variable light chain (VL) connected by a peptide linker, can potentially be used to replace RIG. However, in our previous study, a scFv (scFV57S) specific for the rabies virus (RV) G protein showed a lower neutralizing potency than that of its parent IgG due to lower stability and altered peptide assembly pattern. In monoclonal antibodies, the VH and VL interact non-covalently, while in scFvs the VH is connected covalently with the VL by the artificial linker. In this study, we constructed and expressed two peptides 57VL-JUN-HIS and 57VH-FOS-HA in Escherichia coli. The well-known Fos and Jun leucine zippers were utilized to dimerize VH and VL similarly to the IgG counterpart. The two peptides assembled to form zipFv57S in vitro. Due to the greater similarity in structure with IgG, the zipFv57S protein showed a higher binding ability and affinity resulting in notable improvement of in vitro neutralizing activity over its corresponding scFv. The zipFv57S protein was also found to be more stable and showed similar protective rate as RIG in mice challenged with a lethal dose of RV. Our results not only indicated zipFv57S as an ideal alternative for RIG in PEP but also offered a novel and efficient hetero-dimerization pattern of VH and VL leading to enhanced neutralizing potency. Copyright © 2015. Published by Elsevier Ltd.

  7. Microwave irradiation effects on vermicasts potency, and plant growth and antioxidant activity in seedlings of Chinese cabbage (Brassica rapa subsp. pekinensis

    Directory of Open Access Journals (Sweden)

    Lord Abbey

    2017-04-01

    Full Text Available Vermicasts is rich in beneficial microorganisms and plant growth factors. Unlike soils, the effect of microwave irradiation (MWI on vermicasts potency has not been reported. This study investigated MWI effects on vermicasts potency, plant growth and biochemical activity in Chinese cabbage ‘Bilko’ seedlings. Fresh, moist vermicasts were microwaved at power output levels: 0, 100, 200, 300, 400 and 800 Watts (W. Water loss, nutrients and total aerobic plate content were assessed. A complete randomized design greenhouse experiment was used to evaluate seedlings growth performance and tissue bioactivity. Water loss increased from 5 mg/g (0 W to 215 mg/g (800 W. Total dissolved solids and electrical conductivity of the vermicasts gradually increased with an increase in MWI power output level from 0 to 200 W. This was followed by a steep rise through treatment 300 W and a peak at 400 W. Total nitrogen and nitrate decreased, while ammonia-nitrogen and nitrite-nitrogen increased at higher power levels. Similarly, phosphorus, potassium, magnesium, calcium, manganese, barium and molybdenum contents increased while sodium and barium remained fairly constant. However, MWI irradiation reduced total aerobic plate count by ≥50%. Plant growth and biomass were increased by the 400 W and 800 W MWI treatments. Antioxidant activity was highest in 200, 400 and 800 W treated plants. Collectively the finding indicated that the 400 W treatment increased the bioavailability of nutrients, and represents the best option for plant growth enhancement and improved antioxidant activity.

  8. Protective effects of high-potency FMDV O1 Manisa monovalent vaccine in cattle challenged with FMDV O/SKR/2010 at 7 or 4 days post vaccination.

    Science.gov (United States)

    Horsington, Jacquelyn; Perez, Claudia Beascoechea; Maradei, Eduardo; Novo, Sabrina Galdo; Gonzales, Jose L; Singanallur, Nagendrakumar B; Bonastre, Paula; Vosloo, Wilna

    2017-09-12

    Serotype O foot-and-mouth disease (FMD) virus belonging to the SEA topotype continues to be a significant problem in the Eastern Asia region, with outbreaks in Japan and South Korea resulting in the culling of over 3.5 million cattle and pigs in recent years. High-potency O1 Manisa vaccine was previously shown to provide protection in cattle 21days post vaccination (dpv) following challenge with a representative virus, O/SKR/2010. This study tested the ability of the O1 Manisa vaccine to protect cattle from infection and disease with the O/SKR/2010 virus within just 4 or 7days post vaccination. The vaccine protected 50% of cattle from clinical disease when administered 7days prior to challenge, but was not protective with just 4days between vaccination and challenge. Viraemia was significantly reduced in animals challenged 7 dpv but not 4 dpv, compared to unvaccinated controls, however, there were no effects on the level of virus detected in nasal and oral secretions regardless of vaccination time. The level of neutralising antibodies detected in cattle challenged 7 dpv correlated with protection from clinical disease. All animals seroconverted to FMDV non-structural proteins, suggesting no sterile protection. An equal number of animals became persistently infected in both vaccine groups. The results indicated that high-potency O1 Manisa vaccine administered just 7days prior to challenge should provide partial protection of cattle if an outbreak of O/SKR/2010, or related viruses, occurs, and would be useful to limit spread of FMDV when used in conjunction with other control measures. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Toward Exosome-Based Therapeutics: Isolation, Heterogeneity, and Fit-for-Purpose Potency

    Directory of Open Access Journals (Sweden)

    Gareth R. Willis

    2017-10-01

    Full Text Available Exosomes are defined as submicron (30–150 nm, lipid bilayer-enclosed extracellular vesicles (EVs, specifically generated by the late endosomal compartment through fusion of multivesicular bodies with the plasma membrane. Produced by almost all cells, exosomes were originally considered to represent just a mechanism for jettisoning unwanted cellular moieties. Although this may be a major function in most cells, evolution has recruited the endosomal membrane-sorting pathway to duties beyond mere garbage disposal, one of the most notable examples being its cooption by retroviruses for the generation of Trojan virions. It is, therefore, tempting to speculate that certain cell types have evolved an exosome subclass active in intracellular communication. We term this EV subclass “signalosomes” and define them as exosomes that are produced by the “signaling” cells upon specific physiological or environmental cues and harbor cargo capable of modulating the programming of recipient cells. Our recent studies have established that signalosomes released by mesenchymal stem/stromal cells (MSCs represent the main vector of MSC immunomodulation and therapeutic action in animal models of lung disease. The efficacy of MSC-exosome treatments in a number of preclinical models of cardiovascular and pulmonary disease supports the promise of application of exosome-based therapeutics across a wide range of pathologies within the near future. However, the full realization of exosome therapeutic potential has been hampered by the absence of standardization in EV isolation, and procedures for purification of signalosomes from the main exosome population. This is mainly due to immature methodologies for exosome isolation and characterization and our incomplete understanding of the specific characteristics and molecular composition of signalosomes. In addition, difficulties in defining metrics for potency of exosome preparations and the challenges of industrial

  10. Structure-based lead optimization to improve antiviral potency and ADMET properties of phenyl-1H-pyrrole-carboxamide entry inhibitors targeted to HIV-1 gp120.

    Science.gov (United States)

    Curreli, Francesca; Belov, Dmitry S; Kwon, Young Do; Ramesh, Ranjith; Furimsky, Anna M; O'Loughlin, Kathleen; Byrge, Patricia C; Iyer, Lalitha V; Mirsalis, Jon C; Kurkin, Alexander V; Altieri, Andrea; Debnath, Asim K

    2018-05-12

    We are continuing our concerted effort to optimize our first lead entry antagonist, NBD-11021, which targets the Phe43 cavity of the HIV-1 envelope glycoprotein gp120, to improve antiviral potency and ADMET properties. In this report, we present a structure-based approach that helped us to generate working hypotheses to modify further a recently reported advanced lead entry antagonist, NBD-14107, which showed significant improvement in antiviral potency when tested in a single-cycle assay against a large panel of Env-pseudotyped viruses. We report here the synthesis of twenty-nine new compounds and evaluation of their antiviral activity in a single-cycle and multi-cycle assay to derive a comprehensive structure-activity relationship (SAR). We have selected three inhibitors with the high selectivity index for testing against a large panel of 55 Env-pseudotyped viruses representing a diverse set of clinical isolates of different subtypes. The antiviral activity of one of these potent inhibitors, 55 (NBD-14189), against some clinical isolates was as low as 63 nM. We determined the sensitivity of CD4-binding site mutated-pseudoviruses to these inhibitors to confirm that they target HIV-1 gp120. Furthermore, we assessed their ADMET properties and compared them to the clinical candidate attachment inhibitor, BMS-626529. The ADMET data indicate that some of these new inhibitors have comparable ADMET properties to BMS-626529 and can be optimized further to potential clinical candidates. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  11. Study Of Topical Anti-Inflammatory Potency And Clinical Efficacy Of Formulations Of Mometasone And Betamethasone By Cutaneous Blood Flow Measurements In Psoriatic Patients Using Laser Doppler Velocimetry

    Directory of Open Access Journals (Sweden)

    Mulekar S. V

    1997-01-01

    Full Text Available Laser Doppier Velocimetry (LDV was used to measure cutaneous blood flow (CBF in psoriatic skin lesions to assess the effect of once daily application of Mometasone furoate (MF in a base claimed to possess a “reservoir” effect, as against Betamethasone-17-valarate (BV in a conventional cream base, applied twice daily, for 4 weeks. Bilaterally symmetrical active lesions were studied in 10 psoriatics, at baseline and at the end of 2 and 4 weeks’ treatment. The formulations were also evaluated for topical anti-inflammatory potency in terms of their ability to inhibit the Post-Ischaemic-Reactive-Hyperaemic-Response (PIRHR induced on normal uninvolved skin treated under occlusion. The lesions were also assessed subjectively for clinical Psoriatic Hyperaemia Index (PHI = CBF on lesions/CBF on uninvolved skin: 8.42 + 1.74 & 10.13 + 1.70 correlating with high CPI (9 + 0.50 & 9.1 + 0.51. During treatment with MF or BV, the lesions resolved rapidly, with a concomitant decrease in PHI and CPI (Week 2 : PHI = 3.40 + 0.46 & 5.19 + 1.65, CPI = 4.15 + 0.86& 5.20 + 0.87 and Week 4 : PHI = 1.99 + 0.23 & 2.81 + 0.74 CPI = 2.00 + 0.50 & 2.88 + 0.72 respectively. The two formulations Inhibited PIRHR to same extent (auc/min: Control = 1871 + 399.22, MF = 536.11 + 153.34 & BV = 567.5 + 110.76, indicating equal potency. The results show that pharmaceutical factor such as vehicle can significantly influence the clinical efficacy of corticoids.

  12. [An experimental study on the Chinese lung adenocarcinoma cell clone CPA-Yang1-BR with brain metastasis potency in nude mice and in vivo imaging research].

    Science.gov (United States)

    Lei, Bei; Cao, Jie; Shen, Jie; Zhao, Lanxiang; Liang, Sheng; Meng, Qinggang; Xie, Wenhui; Yang, Shunfang

    2013-08-20

    Lung cancer is the leading cause of cancer-related death in men and women. It is also the most common cause of brain metastases. A brain metastasis model is difficult to be established because of the presence of the blood-brain barrier (BBB) and the lack of optimal methods for detecting brain metastasis in nude mice. Thus, the establishment of a Chinese lung adenocarcinoma cell line and its animal model with brain metastasis potency and in vivo research is of great significance. CPA-Yang1 cells were obtained from a patient with human lung adenocarcinoma by lentiviral vector-mediated transfection of green fluorescence protein. Intracardiac inoculation of the cells was performed in nude mice, and brain metastatic lesions were detected using micro ¹⁸F FDG-PET/CT scanners, small animal in vivo imaging system for fluorescence, radionuclide and X ray fused imaging, magnetic resonance imaging (MRI) with sense body detection, and resection. The samples were divided into two parts for cell culture and histological diagnosis. The process was repeated in vivo and in vitro for four cycles to obtain a novel cell clone, CPA-Yang1-BR. A novel cell clone, CPA-Yang1-BR, was obtained with a brain metastatic rate of 50%. The use of MRI for the detection of brain metastases has obvious advantages. An experimental Chinese lung adenocarcinoma cell clone (CPA-Yang1-BR) and its animal model with brain metastasis potency in nude mice were established. MRI with sense body or micro MRI may be used as a sensitive, accurate, and noninvasive method to detect experimental brain metastases in intact live immunodeficient mice. The results of this study may serve as a technical platform for brain metastases from lung adenocarcinoma.

  13. Radiosensitivity of higher plants

    International Nuclear Information System (INIS)

    Feng Zhijie

    1992-11-01

    The general views on radiosensitivity of higher plants have been introduced from published references. The radiosensitivity varies with species, varieties and organs or tissues. The main factors of determining the radiosensitivity in different species are nucleus volume, chromosome volume, DNA content and endogenous compounds. The self-repair ability of DNA damage and chemical group of biological molecules, such as -SH thiohydroxy of proteins, are main factors to determine the radiosensitivity in different varieties. The moisture, oxygen, temperature radiosensitizer and protector are important external factors for radiosensitivity. Both the multiple target model and Chadwick-Leenhouts model are ideal mathematical models for describing the radiosensitivity of higher plants and the latter has more clear significance in biology

  14. Factors mediating lipofection potency of a series of cationic phosphonolipids in human cell lines.

    Science.gov (United States)

    Koumbi, Daphne; Clement, Jean-Claude; Sideratou, Zili; Yaouanc, Jean-Jacques; Loukopoulos, Dimitris; Kollia, Panagoula

    2006-08-01

    A series of cationic liposomes known as cationic phosphonolipids (CPs) were evaluated as vehicles for in vitro gene transfer in K562 erythroleukemia cells and 5637 epithelial carcinoma cells. For each CP and target cell type examined, detailed analyses were performed to determine optimal transfection conditions (lipid/ DNA (+/-) charge ratio, amount of complexed episomal DNA, liposomal and lipoplex size, complexation medium and duration of complex-cell exposure time). Lipofection conditions were determined to be both cell- and lipid-type specific. Complexation medium critically affected transfection competence. The initial size of the liposome was not always predictive of lipofection potency. The lipid chemical composition had a strong impact upon lipofection efficiency; DOPE inclusion in the liposome formulations was found to affect the levels of transgene expression in a cell-dependent way. Notably, effective transgene expression was characterized by prominent plasmid nuclear incorporation. Human A gamma- and epsilon-globin transgene nuclear incorporation and expression in 5637 cells post GLB.391-mediated lipofection lends credence to its use as a vehicle of therapeutic transgene delivery.

  15. The glycaemic potency of breakfast and cognitive function in school children.

    Science.gov (United States)

    Micha, R; Rogers, P J; Nelson, M

    2010-09-01

    The aim of this study was to assess how the glycaemic potency (blood glucose (BG)-raising potential) of breakfast is associated with cognitive function (CF) in school children, taking into account important confounders, including iron status, underlying physiological adaptations and socio-economic status. Sixty children aged 11-14 years were selected on the basis of having breakfast habitually. Their breakfast and any snacks eaten on the morning of the study were recorded. They were categorized into four groups according to the glycaemic index (GI) and glycaemic load (GL) of the breakfast: low-GI, high-GL; high-GI, high-GL; low-GI, low-GL and high-GI, low-GL above or below the median for GI=61 and GL=27. BG levels were measured in finger-prick blood samples immediately before and immediately after the CF tests. A low-GI, high-GL breakfast was associated with better performance on a speed of information processing (Pbreakfast with better performance on an immediate word recall task (Pbreakfast with better performance on a Matrices task (Pperformance on the majority of the CF tests (4 of 7) used. This study describes the macronutrient composition of breakfast that could have a positive influence on the cognition of school children, proposes the use of both GI and GL to estimate exposure, and discusses future directions in this area of research.

  16. Free radical scavenging potency of quercetin catecholic colonic metabolites: Thermodynamics of 2H+/2e- processes.

    Science.gov (United States)

    Amić, Ana; Lučić, Bono; Stepanić, Višnja; Marković, Zoran; Marković, Svetlana; Dimitrić Marković, Jasmina M; Amić, Dragan

    2017-03-01

    Reaction energetics of the double (2H + /2e - ), i.e., the first 1H + /1e - (catechol→ phenoxyl radical) and the second 1H + /1e - (phenoxyl radical→ quinone) free radical scavenging mechanisms of quercetin and its six colonic catecholic metabolites (caffeic acid, hydrocaffeic acid, homoprotocatechuic acid, protocatechuic acid, 4-methylcatechol, and catechol) were computationally studied using density functional theory, with the aim to estimate the antiradical potency of these molecules. We found that second hydrogen atom transfer (HAT) and second sequential proton loss electron transfer (SPLET) mechanisms are less energy demanding than the first ones indicating 2H + /2e - processes as inherent to catechol moiety. The Gibbs free energy change for reactions of inactivation of selected free radicals indicate that catecholic colonic metabolites constitute an efficient group of more potent scavengers than quercetin itself, able to deactivate various free radicals, under different biological conditions. They could be responsible for the health benefits associated with regular intake of flavonoid-rich diet. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Development of a Sweetness Sensor for Aspartame, a Positively Charged High-Potency Sweetener

    Directory of Open Access Journals (Sweden)

    Masato Yasuura

    2014-04-01

    Full Text Available Taste evaluation technology has been developed by several methods, such as sensory tests, electronic tongues and a taste sensor based on lipid/polymer membranes. In particular, the taste sensor can individually quantify five basic tastes without multivariate analysis. However, it has proven difficult to develop a sweetness sensor, because sweeteners are classified into three types according to the electric charges in an aqueous solution; that is, no charge, negative charge and positive charge. Using membrane potential measurements, the taste-sensing system needs three types of sensor membrane for each electric charge type of sweetener. Since the commercially available sweetness sensor was only intended for uncharged sweeteners, a sweetness sensor for positively charged high-potency sweeteners such as aspartame was developed in this study. Using a lipid and plasticizers, we fabricated various lipid/polymer membranes for the sweetness sensor to identify the suitable components of the sensor membranes. As a result, one of the developed sensors showed responses of more than 20 mV to 10 mM aspartame and less than 5 mV to any other taste. The responses of the sensor depended on the concentration of aspartame. These results suggested that the developed sweetness sensor had high sensitivity to and high selectivity for aspartame.

  18. Enhanced Delivery and Potency of Self-Amplifying mRNA Vaccines by Electroporation in Situ

    Directory of Open Access Journals (Sweden)

    Kaustuv Banerjee

    2013-08-01

    Full Text Available Nucleic acid-based vaccines such as viral vectors, plasmid DNA (pDNA, and mRNA are being developed as a means to address limitations of both live-attenuated and subunit vaccines. DNA vaccines have been shown to be potent in a wide variety of animal species and several products are now licensed for commercial veterinary but not human use. Electroporation delivery technologies have been shown to improve the generation of T and B cell responses from synthetic DNA vaccines in many animal species and now in humans. However, parallel RNA approaches have lagged due to potential issues of potency and production. Many of the obstacles to mRNA vaccine development have recently been addressed, resulting in a revival in the use of non-amplifying and self-amplifying mRNA for vaccine and gene therapy applications. In this paper, we explore the utility of EP for the in vivo delivery of large, self-amplifying mRNA, as measured by reporter gene expression and immunogenicity of genes encoding HIV envelope protein. These studies demonstrated that EP delivery of self-amplifying mRNA elicited strong and broad immune responses in mice, which were comparable to those induced by EP delivery of pDNA.

  19. Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors.

    Science.gov (United States)

    Thorsell, Ann-Gerd; Ekblad, Torun; Karlberg, Tobias; Löw, Mirjam; Pinto, Ana Filipa; Trésaugues, Lionel; Moche, Martin; Cohen, Michael S; Schüler, Herwig

    2017-02-23

    Selective inhibitors could help unveil the mechanisms by which inhibition of poly(ADP-ribose) polymerases (PARPs) elicits clinical benefits in cancer therapy. We profiled 10 clinical PARP inhibitors and commonly used research tools for their inhibition of multiple PARP enzymes. We also determined crystal structures of these compounds bound to PARP1 or PARP2. Veliparib and niraparib are selective inhibitors of PARP1 and PARP2; olaparib, rucaparib, and talazoparib are more potent inhibitors of PARP1 but are less selective. PJ34 and UPF1069 are broad PARP inhibitors; PJ34 inserts a flexible moiety into hydrophobic subpockets in various ADP-ribosyltransferases. XAV939 is a promiscuous tankyrase inhibitor and a potent inhibitor of PARP1 in vitro and in cells, whereas IWR1 and AZ-6102 are tankyrase selective. Our biochemical and structural analysis of PARP inhibitor potencies establishes a molecular basis for either selectivity or promiscuity and provides a benchmark for experimental design in assessment of PARP inhibitor effects.

  20. Tetraploid Embryonic Stem Cells Maintain Pluripotency and Differentiation Potency into Three Germ Layers.

    Directory of Open Access Journals (Sweden)

    Hiroyuki Imai

    Full Text Available Polyploid amphibians and fishes occur naturally in nature, while polyploid mammals do not. For example, tetraploid mouse embryos normally develop into blastocysts, but exhibit abnormalities and die soon after implantation. Thus, polyploidization is thought to be harmful during early mammalian development. However, the mechanisms through which polyploidization disrupts development are still poorly understood. In this study, we aimed to elucidate how genome duplication affects early mammalian development. To this end, we established tetraploid embryonic stem cells (TESCs produced from the inner cell masses of tetraploid blastocysts using electrofusion of two-cell embryos in mice and studied the developmental potential of TESCs. We demonstrated that TESCs possessed essential pluripotency and differentiation potency to form teratomas, which differentiated into the three germ layers, including diploid embryonic stem cells. TESCs also contributed to the inner cell masses in aggregated chimeric blastocysts, despite the observation that tetraploid embryos fail in normal development soon after implantation in mice. In TESCs, stability after several passages, colony morphology, and alkaline phosphatase activity were similar to those of diploid ESCs. TESCs also exhibited sufficient expression and localization of pluripotent markers and retained the normal epigenetic status of relevant reprogramming factors. TESCs proliferated at a slower rate than ESCs, indicating that the difference in genomic dosage was responsible for the different growth rates. Thus, our findings suggested that mouse ESCs maintained intrinsic pluripotency and differentiation potential despite tetraploidization, providing insights into our understanding of developmental elimination in polyploid mammals.

  1. Isolation and Pharmacological Evaluation of Minor Cannabinoids from High-Potency Cannabis sativa.

    Science.gov (United States)

    Radwan, Mohamed M; ElSohly, Mahmoud A; El-Alfy, Abir T; Ahmed, Safwat A; Slade, Desmond; Husni, Afeef S; Manly, Susan P; Wilson, Lisa; Seale, Suzanne; Cutler, Stephen J; Ross, Samir A

    2015-06-26

    Seven new naturally occurring hydroxylated cannabinoids (1-7), along with the known cannabiripsol (8), have been isolated from the aerial parts of high-potency Cannabis sativa. The structures of the new compounds were determined by 1D and 2D NMR spectroscopic analysis, GC-MS, and HRESIMS as 8α-hydroxy-Δ(9)-tetrahydrocannabinol (1), 8β-hydroxy-Δ(9)-tetrahydrocannabinol (2), 10α-hydroxy-Δ(8)-tetrahydrocannabinol (3), 10β-hydroxy-Δ(8)-tetrahydrocannabinol (4), 10α-hydroxy-Δ(9,11)-hexahydrocannabinol (5), 9β,10β-epoxyhexahydrocannabinol (6), and 11-acetoxy-Δ(9)-tetrahydrocannabinolic acid A (7). The binding affinity of isolated compounds 1-8, Δ(9)-tetrahydrocannabinol, and Δ(8)-tetrahydrocannabinol toward CB1 and CB2 receptors as well as their behavioral effects in a mouse tetrad assay were studied. The results indicated that compound 3, with the highest affinity to the CB1 receptors, exerted the most potent cannabimimetic-like actions in the tetrad assay, while compound 4 showed partial cannabimimetic actions. Compound 2, on the other hand, displayed a dose-dependent hypolocomotive effect only.

  2. Antifungal Activity of the Volatiles of High Potency Cannabis sativa L. Against Cryptococcus neoformans

    Directory of Open Access Journals (Sweden)

    Amira S. Wanas

    2016-03-01

    Full Text Available The n-hexane extracted volatile fraction of high potency Cannabis sativa L (Cannabaceae . was assessed in vitro for antifungal, antibacterial and antileishmanial activities. The oil exhibited selective albeit modest, antifungal activity against Cryptococcus neoformans with an IC 50 value of 33.1 µg/mL. Biologically-guided fractionation of the volatile fraction resulted in the isolation of three major compounds (1-3 using various chromatographic techniques. The chemical structures of the isolated compounds were identified as α-humulene (1, b -caryophyllene (2 and caryophyllene oxide (3 using GC/FID, GC/MS, 1D- and 2D-NMR analyses, respectively. Compound 1 showed potent and selective antifungal activity against Cryptococcus neoformans with IC 50 and MIC values of 1.18 m g/mL and 5.0 m g/mL respectively. Whereas compound 2 showed weak activity (IC 50 19.4 µg/mL, while compound 3 was inactive against C. neoformans.

  3. Understanding the toxic potencies of xenobiotics inducing TCDD/TCDF-like effects.

    Science.gov (United States)

    Şahin, A D; Saçan, M T

    2018-02-01

    Toxic potencies of xenobiotics such as halogenated aromatic hydrocarbons inducing 2,3,7,8-tetrachlorodibenzo-p-dioxin/2,3,7,8-tetrachlorodibenzofuran (TCDD/TCDF)-like effects were investigated by quantitative structure-toxicity relationships (QSTR) using their aryl hydrocarbon receptor (AhR) binding affinity data. A descriptor pool was created using the SPARTAN 10, DRAGON 6.0 and ADMET 8.0 software packages, and the descriptors were selected using QSARINS (v.2.2.1) software. The QSTR models generated for AhR binding affinities of chemicals with TCDD/TCDF-like effects were internally and externally validated in line with the Organization of Economic Co-operation and Development (OECD) principles. The TCDD-based model had six descriptors from DRAGON 6.0 and ADMET 8.0, whereas the TCDF-based model had seven descriptors from DRAGON 6.0. The predictive ability of the generated models was tested on a diverse group of chemicals including polychlorinated/brominated biphenyls, dioxins/furans, ethers, polyaromatic hydrocarbons with fused heterocyclic rings (i.e. phenoxathiins, thianthrenes and dibenzothiophenes) and polyaromatic hydrocarbons (i.e. halogenated naphthalenes and phenanthrenes) with no AhR binding data. For the external set chemicals, the structural coverage of the generated models was 90% and 89% for TCDD and TCDF-like effects, respectively.

  4. Reducing animal experimentation in foot-and-mouth disease vaccine potency tests.

    Science.gov (United States)

    Reeve, Richard; Cox, Sarah; Smitsaart, Eliana; Beascoechea, Claudia Perez; Haas, Bernd; Maradei, Eduardo; Haydon, Daniel T; Barnett, Paul

    2011-07-26

    The World Organisation for Animal Health (OIE) Terrestrial Manual and the European Pharmacopoeia (EP) still prescribe live challenge experiments for foot-and-mouth disease virus (FMDV) immunogenicity and vaccine potency tests. However, the EP allows for other validated tests for the latter, and specifically in vitro tests if a "satisfactory pass level" has been determined; serological replacements are also currently in use in South America. Much research has therefore focused on validating both ex vivo and in vitro tests to replace live challenge. However, insufficient attention has been given to the sensitivity and specificity of the "gold standard"in vivo test being replaced, despite this information being critical to determining what should be required of its replacement. This paper aims to redress this imbalance by examining the current live challenge tests and their associated statistics and determining the confidence that we can have in them, thereby setting a standard for candidate replacements. It determines that the statistics associated with the current EP PD(50) test are inappropriate given our domain knowledge, but that the OIE test statistics are satisfactory. However, it has also identified a new set of live animal challenge test regimes that provide similar sensitivity and specificity to all of the currently used OIE tests using fewer animals (16 including controls), and can also provide further savings in live animal experiments in exchange for small reductions in sensitivity and specificity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Geology of Muntok area and the potency of menumbang granite as source of Uranium and Thorium

    International Nuclear Information System (INIS)

    Kurniawan Dwi Saksama; Ngadenin

    2013-01-01

    In the West Bangka there are some granites namely Menumbing, Pelangas, Tempilang, and Jebus granite. The granites is granite tin belt that stretches from Thailand-Malaysia-Bangka Belitung. Granite tin belt or granite source of tin (cassiterite) can act as a source of U and Th. Aims of the study is to find out the information on the geology of Muntok area and its surrounding and to determine the potency of Menumbing granite as a source of U and Th. The methods used is surface geological mapping in Muntok areas and its surrounding with scale 1 : 25.000, measurement grade of uranium and thorium in Menumbing granite areas and petrographic and grain size analysis of sample of Menumbing granite. Determination of granites a source of U and Th is based on content of radioactive mineral, anomaly of U and Th, megascopic and microscopic observation of granite. Morphology of Muntok areas and its surrounding is denudasional undulating plains to hills with an elevation ranging from 0 to 455 meters. Stratigraphy of research areas from old to young is meta sandstone units, granite intrusion of Menumbing and alluvial. Evolving fault is a fault trending West-East. Based on the presence of radioactive minerals, grade of U and Th as well as the type of granite, it was concluded that the Menumbing granite is a source of Th and not sources of U. (author)

  6. POTENCY AND DEVELOPMENT STRATEGY OF SPOTTED BUFFALO IN SANGGALANGI SUBDISTRICT, NORTH TORAJA DISTRICT, SOUTH SULAWESI

    Directory of Open Access Journals (Sweden)

    K. Komariah

    2014-10-01

    Full Text Available The aim of this research was to analyze the reproduction performances, potency and developmentstrategy of Torajan's spotted buffalo. This research was done from July to September 2010 inSanggalangi’ subdistrict, North Toraja district, South Sulawesi. Purposive sampling was applied toobserve data. The primary data were taken by purposive sampling method and collected by interview of90 farmers. Results showed that sex ratio of male-female was 3:2. The first estrus was 2.48 years old,the estrus period was 23 hours and the oestrus cycle was 19 days. The first mating was 2.87 years oldwith the conception period about 387 days. Furthermore, the first partus was at 3.74 years old, calvinginterval was 2 years. Calving rate and calf crops were relatively high. Calf crops were 77%, pre weaningmortality was 2.35%. Service per conception (S/C was 1.85 and conception rate (CR was 86.5%. Themost livelihoods in North Toraja is farmer. Spotted Buffalo population declined 24.31 % per year.SWOT analysis showed that score for internal factor was -0.25, whereas external factor was 2.25. It wasshowed that the sub-district Sanggalangi is in turnaround condition, so the development strategy ofTorajan’s spotted buffalo has to minimize the weakness and reached the opportunities.

  7. Tetraploid Embryonic Stem Cells Maintain Pluripotency and Differentiation Potency into Three Germ Layers.

    Science.gov (United States)

    Imai, Hiroyuki; Kano, Kiyoshi; Fujii, Wataru; Takasawa, Ken; Wakitani, Shoichi; Hiyama, Masato; Nishino, Koichiro; Kusakabe, Ken Takeshi; Kiso, Yasuo

    2015-01-01

    Polyploid amphibians and fishes occur naturally in nature, while polyploid mammals do not. For example, tetraploid mouse embryos normally develop into blastocysts, but exhibit abnormalities and die soon after implantation. Thus, polyploidization is thought to be harmful during early mammalian development. However, the mechanisms through which polyploidization disrupts development are still poorly understood. In this study, we aimed to elucidate how genome duplication affects early mammalian development. To this end, we established tetraploid embryonic stem cells (TESCs) produced from the inner cell masses of tetraploid blastocysts using electrofusion of two-cell embryos in mice and studied the developmental potential of TESCs. We demonstrated that TESCs possessed essential pluripotency and differentiation potency to form teratomas, which differentiated into the three germ layers, including diploid embryonic stem cells. TESCs also contributed to the inner cell masses in aggregated chimeric blastocysts, despite the observation that tetraploid embryos fail in normal development soon after implantation in mice. In TESCs, stability after several passages, colony morphology, and alkaline phosphatase activity were similar to those of diploid ESCs. TESCs also exhibited sufficient expression and localization of pluripotent markers and retained the normal epigenetic status of relevant reprogramming factors. TESCs proliferated at a slower rate than ESCs, indicating that the difference in genomic dosage was responsible for the different growth rates. Thus, our findings suggested that mouse ESCs maintained intrinsic pluripotency and differentiation potential despite tetraploidization, providing insights into our understanding of developmental elimination in polyploid mammals.

  8. POTENCY AND DEVELOPMENT STRATEGY OF SPOTTED BUFFALO IN SANGGALANGI SUBDISTRICT, NORTH TORAJA DISTRICT, SOUTH SULAWESI

    Directory of Open Access Journals (Sweden)

    D. J. Setyono

    2012-06-01

    Full Text Available The aim of this research was to analyze the reproduction performances, potency and development strategy of Torajans spotted buffalo. This research was done from July to September 2010 in Sanggalangi subdistrict, North Toraja district, South Sulawesi. Purposive sampling was applied to observe data. The primary data were taken by purposive sampling method and collected by interview of 90 farmers. Results showed that sex ratio of male-female was 3:2. The first estrus was 2.48 years old, the estrus period was 23 hours and the oestrus cycle was 19 days. The first mating was 2.87 years old with the conception period about 387 days. Furthermore, the first partus was at 3.74 years old, calving interval was 2 years. Calving rate and calf crops were relatively high. Calf crops were 77%, pre weaning mortality was 2.35%. Service per conception (S/C was 1.85 and conception rate (CR was 86.5%. The most livelihoods in North Toraja is farmer. Spotted Buffalo population declined 24.31 % per year. SWOT analysis showed that score for internal factor was -0.25, whereas external factor was 2.25. It was showed that the sub-district Sanggalangi is in turnaround condition, so the development strategy of Torajans spotted buffalo has to minimize the weakness and reached the opportunities.

  9. Composition and Potency Characterization of Mycobacterium avium subsp. paratuberculosis Purified Protein Derivatives.

    Directory of Open Access Journals (Sweden)

    Randal T Capsel

    Full Text Available Mycobacterium avium subsp. paratuberculosis (MAP purified protein derivatives (PPDs are immunologic reagents prepared from cultured filtrates of the type strain. Traditional production consists of floating culture incubation at 37°C, organism inactivation by autoclaving, coarse filtration, and protein precipitation. Three traditional production PPDs were used in this study including lot 9801, which served as a reference and has been used in the field for decades. Alternative production PPDs (0902A and 0902B, in which the autoclaving step was removed, were also analyzed in this study. SDS-PAGE analysis revealed protein smearing in traditional PPDs, but distinct bands were observed in the alternative PPD preparations. Antibody bound distinct protein bands in the alternative PPDs by immunoblot analysis, whereas an immunoreactive smear was observed with the traditional PPDs. Mass spectrometry identified 194 proteins among three PPD lots representing the two different production methods, ten of which were present in all PPDs examined. Selected proteins identified by mass spectrometry were recombinantly expressed and purified from E. coli and evaluated by the guinea pig potency test. Seven recombinant proteins showed greater erythema as compared to the reference PPD lot 9801 in paired guinea pigs and were able to stimulate interferon-gamma production in blood from Johne's positive animals. These results suggest that autoclaving culture suspensions is not a necessary step in PPD production and specific proteins could supplant the PPD antigen for intradermal skin testing procedures and for use as in-vitro assay reagents.

  10. Development of a sweetness sensor for aspartame, a positively charged high-potency sweetener.

    Science.gov (United States)

    Yasuura, Masato; Tahara, Yusuke; Ikezaki, Hidekazu; Toko, Kiyoshi

    2014-04-23

    Taste evaluation technology has been developed by several methods, such as sensory tests, electronic tongues and a taste sensor based on lipid/polymer membranes. In particular, the taste sensor can individually quantify five basic tastes without multivariate analysis. However, it has proven difficult to develop a sweetness sensor, because sweeteners are classified into three types according to the electric charges in an aqueous solution; that is, no charge, negative charge and positive charge. Using membrane potential measurements, the taste-sensing system needs three types of sensor membrane for each electric charge type of sweetener. Since the commercially available sweetness sensor was only intended for uncharged sweeteners, a sweetness sensor for positively charged high-potency sweeteners such as aspartame was developed in this study. Using a lipid and plasticizers, we fabricated various lipid/polymer membranes for the sweetness sensor to identify the suitable components of the sensor membranes. As a result, one of the developed sensors showed responses of more than 20 mV to 10 mM aspartame and less than 5 mV to any other taste. The responses of the sensor depended on the concentration of aspartame. These results suggested that the developed sweetness sensor had high sensitivity to and high selectivity for aspartame.

  11. Quantification of antibiotic drug potency by a two-compartment radioassay of bacterial growth

    International Nuclear Information System (INIS)

    Boonkitticharoen, V.; Ehrhardt, J.C.; Kirchner, P.T.

    1990-01-01

    The two-compartment radioassay for microbial kinetics based on continuous measurement of the 14 CO 2 released by bacterial metabolism of 14C-labeled substrate offers a valuable approach to testing the potency of antimicrobial drugs. By using a previously validated radioassay with gram-positive and gram-negative bacteria, a group of protein synthesis inhibitors was evaluated for their effect on microbial growth kinetics. All tested drugs induced changes in both the slopes and intercepts of the growth curves. An exponential growth model was applied to quantify the drug effect on the processes of bacterial 14 CO 2 liberation and cell generation. The response was measured in terms of a generation rate constant. A linear dependence of the generation rate constant on the dose of spectinomycin was observed with Escherichia coli. Sigmoidal-shaped curves were found in the assays of chloramphenicol and tetracycline. The implications of dose-response curves are discussed on the basis of the receptor site concept for drug action. The assay sensitivities for chloramphenicol and tetracycline were similar to those obtained by the cell counting method, but the sensitivity of the radioassay was at least 10 times greater for spectinomycin

  12. Invitro Assessment of Bacteriostatic Potency of Egg Yolk Immunoglobulin against Escherichia coli

    Directory of Open Access Journals (Sweden)

    Vikrama Chakravarthi. P1

    Full Text Available The present study was carried out in commercial layer chickens to assess the bacteriostatic potency of egg yolk immunoglobulin IgY against food poisoning pathogen. The O antigen of food poisoning pathogen Escherichia coli was prepared and used to immunize commercial layer chickens. The eggs which contain anti-E.Coli IgY was collected on 30 th day of first injection and stored at 4 0 C. The antibacterial IgY was separated by water dilution method (10 times diluted with distilled water, pH 5.0 - 5.5, incubated at 4 0 C for 6 hrs and purified by 60 % ammonium sulphate. The recovery of IgY was in range of 57-62 %. The pathogens in Tryptic soya broth (approx. 6X108/ ml were cultured with anti-E.coli IgY @ 20 mg /ml and inhibitory effect was measured in UV spectrophotometer at 550 nm. The resultant growth curve indicated that the application of polyclonal antibodies (Ig Y on meat could be used to prevent the E.coli food poisoning. [Veterinary World 2010; 3(10.000: 460-462

  13. Review of the use of high potencies in basic research on homeopathy.

    Science.gov (United States)

    Clausen, Jürgen; van Wijk, Roeland; Albrecht, Henning

    2011-10-01

    The HomBRex database includes details of about 1500 basic research experiments in homeopathy. A general overview on the experiments listed in the HomBRex database is presented, focusing on high dilutions and the different settings in which those were used. Though often criticised, many experiments with remedies diluted beyond Avogadro's number demonstrate specific effects. A total of 830 experiments employing high potencies was found; in 745 experiments of these (90%), at least one positive result was reported. Animals represent the most often used model system (n=371), followed by plants (n=201), human material (n=92), bacteria and viruses (n=37) and fungi (n=32). Arsenicum album (Ars.) is the substance most often applied (n=101), followed by Sulphur (Sulph.) and Thuja (Thuj.) (n=65 and 48, respectively). Proving, prophylactic and therapeutic study designs have all been used and appear appropriate for homeopathy basic research using high dilutions. The basic research data set to support specific effects unique to high dilutions and opposite to those observed with low dilutions is, to date, insufficient. Copyright © 2011 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

  14. Systematic review: The potency of Zataria multiflora Boiss in treatment of vaginal infections

    Directory of Open Access Journals (Sweden)

    Mohaddese Mahboubi Mahboubi

    2018-04-01

    Full Text Available Vaginitis as female infectious disease is accompanied with some clinical symptoms such as vaginal abnormal discharges, itching, burning and many other unpleasant signs in patients. The responsable microorganisms in vaginitis are belonged to different kind of microorganisms including bacteria (Gardenella vaginitis, yeast (Candida albicans and protozoa (Trichomonas vaginalis. The current treatments of these infections are chemical oral and vaginal drugs with many adverse effects for patients. Furthermore, appearance of resistant microorganisms to these drugs has intensified the treatment’s problem. The aim of this review article was to evaluate the potency of “Zataria multiflora” essential oil in treatment of women’s vaginitis. For preparing this manuscript, the information was extracted from different electronic and published resources. Investigation in different resources showed there were 6 clinical trials that evaluate it as suitable treatment for vaginitis. 5 clinical studies have been focused on 0.1% Z. multiflora essential oils in treatment of bacterial vaginosis (n=1, candidiasis (n=1 and trichomoniasis (n=1. Two clinical studies were related to treatments of bacterial vaginosis, trichomoniasis and mixed infection. There is one clinical study for treatment of candidiasis by 1% Z. multiflora methanol extract. Z. multiflora was formulated in cream form and applied for 5-7 continuous days. The results of clinical trials showed that Z. multiflora essential oil (0.1% can be used as safe and efficient alternative treatment for treatment of bacterial vaginosis, candidiasis and to a lesser extent for trichomoniasis.

  15. Functions of Heterogeneous Nuclear Ribonucleoproteins in Stem Cell Potency and Differentiation

    Directory of Open Access Journals (Sweden)

    Qishan Chen

    2013-01-01

    Full Text Available Stem cells possess huge importance in developmental biology, disease modelling, cell replacement therapy, and tissue engineering in regenerative medicine because they have the remarkable potential for self-renewal and to differentiate into almost all the cell types in the human body. Elucidation of molecular mechanisms regulating stem cell potency and differentiation is essential and critical for extensive application. Heterogeneous nuclear ribonucleoproteins (hnRNPs are modular proteins consisting of RNA-binding motifs and auxiliary domains characterized by extensive and divergent functions in nucleic acid metabolism. Multiple roles of hnRNPs in transcriptional and posttranscriptional regulation enable them to be effective gene expression regulators. More recent findings show that hnRNP proteins are crucial factors implicated in maintenance of stem cell self-renewal and pluripotency and cell differentiation. The hnRNPs interact with certain sequences in target gene promoter regions to initiate transcription. In addition, they recognize 3′UTR or 5′UTR of specific gene mRNA forming mRNP complex to regulate mRNA stability and translation. Both of these regulatory pathways lead to modulation of gene expression that is associated with stem cell proliferation, cell cycle control, pluripotency, and committed differentiation.

  16. POTENCY OF MUNG BEAN SPROUT AS ENZYME SOURCE (α-AMILASE

    Directory of Open Access Journals (Sweden)

    Suarni Suarni

    2010-06-01

    Full Text Available Mung bean sprouts contain enzyme of α-amylase. A research on the effect of the sprout age and sprout varieties to the α-amylase activity and the protein level has been carried out in Laboratorium Bioproses BB Pascapanen Bogor using  Full Factorial Random Design with two factorials (1 sprout age; 1, 2, 3, 4, and 5 days as well as (2 varieties of mung bean; Kenari, Bhakti and Parkit.  Parameters observed were water and protein content of sprout, pH, activities of α-amylase, and dissolved protein in the enzyme extract. Results showed that the optimum temperature of α-amylase was 30 ºC, the highest protein level of sprout and the highest activity of α-amylase were given by the sprout of Bhakti at the age of three days. The water content in sprout was 65.23%, the protein level was 12.93 %, the dissolved protein in the enzyme extract was 2.88743 mg/mL, pH was 5.45, and the activity of enzyme was 4.09 Unit/mL. The potency of enzyme found in mung bean can be utilized in industries processing materials having high starch content, such as maize flour.   Keywords;  sprout of mung bean, activity of α-amylase, protein

  17. Significant Tsunami Events

    Science.gov (United States)

    Dunbar, P. K.; Furtney, M.; McLean, S. J.; Sweeney, A. D.

    2014-12-01

    Tsunamis have inflicted death and destruction on the coastlines of the world throughout history. The occurrence of tsunamis and the resulting effects have been collected and studied as far back as the second millennium B.C. The knowledge gained from cataloging and examining these events has led to significant changes in our understanding of tsunamis, tsunami sources, and methods to mitigate the effects of tsunamis. The most significant, not surprisingly, are often the most devastating, such as the 2011 Tohoku, Japan earthquake and tsunami. The goal of this poster is to give a brief overview of the occurrence of tsunamis and then focus specifically on several significant tsunamis. There are various criteria to determine the most significant tsunamis: the number of deaths, amount of damage, maximum runup height, had a major impact on tsunami science or policy, etc. As a result, descriptions will include some of the most costly (2011 Tohoku, Japan), the most deadly (2004 Sumatra, 1883 Krakatau), and the highest runup ever observed (1958 Lituya Bay, Alaska). The discovery of the Cascadia subduction zone as the source of the 1700 Japanese "Orphan" tsunami and a future tsunami threat to the U.S. northwest coast, contributed to the decision to form the U.S. National Tsunami Hazard Mitigation Program. The great Lisbon earthquake of 1755 marked the beginning of the modern era of seismology. Knowledge gained from the 1964 Alaska earthquake and tsunami helped confirm the theory of plate tectonics. The 1946 Alaska, 1952 Kuril Islands, 1960 Chile, 1964 Alaska, and the 2004 Banda Aceh, tsunamis all resulted in warning centers or systems being established.The data descriptions on this poster were extracted from NOAA's National Geophysical Data Center (NGDC) global historical tsunami database. Additional information about these tsunamis, as well as water level data can be found by accessing the NGDC website www.ngdc.noaa.gov/hazard/

  18. Testing Significance Testing

    Directory of Open Access Journals (Sweden)

    Joachim I. Krueger

    2018-04-01

    Full Text Available The practice of Significance Testing (ST remains widespread in psychological science despite continual criticism of its flaws and abuses. Using simulation experiments, we address four concerns about ST and for two of these we compare ST’s performance with prominent alternatives. We find the following: First, the 'p' values delivered by ST predict the posterior probability of the tested hypothesis well under many research conditions. Second, low 'p' values support inductive inferences because they are most likely to occur when the tested hypothesis is false. Third, 'p' values track likelihood ratios without raising the uncertainties of relative inference. Fourth, 'p' values predict the replicability of research findings better than confidence intervals do. Given these results, we conclude that 'p' values may be used judiciously as a heuristic tool for inductive inference. Yet, 'p' values cannot bear the full burden of inference. We encourage researchers to be flexible in their selection and use of statistical methods.

  19. Safety significance evaluation system

    International Nuclear Information System (INIS)

    Lew, B.S.; Yee, D.; Brewer, W.K.; Quattro, P.J.; Kirby, K.D.

    1991-01-01

    This paper reports that the Pacific Gas and Electric Company (PG and E), in cooperation with ABZ, Incorporated and Science Applications International Corporation (SAIC), investigated the use of artificial intelligence-based programming techniques to assist utility personnel in regulatory compliance problems. The result of this investigation is that artificial intelligence-based programming techniques can successfully be applied to this problem. To demonstrate this, a general methodology was developed and several prototype systems based on this methodology were developed. The prototypes address U.S. Nuclear Regulatory Commission (NRC) event reportability requirements, technical specification compliance based on plant equipment status, and quality assurance assistance. This collection of prototype modules is named the safety significance evaluation system

  20. Predicting significant torso trauma.

    Science.gov (United States)

    Nirula, Ram; Talmor, Daniel; Brasel, Karen

    2005-07-01

    Identification of motor vehicle crash (MVC) characteristics associated with thoracoabdominal injury would advance the development of automatic crash notification systems (ACNS) by improving triage and response times. Our objective was to determine the relationships between MVC characteristics and thoracoabdominal trauma to develop a torso injury probability model. Drivers involved in crashes from 1993 to 2001 within the National Automotive Sampling System were reviewed. Relationships between torso injury and MVC characteristics were assessed using multivariate logistic regression. Receiver operating characteristic curves were used to compare the model to current ACNS models. There were a total of 56,466 drivers. Age, ejection, braking, avoidance, velocity, restraints, passenger-side impact, rollover, and vehicle weight and type were associated with injury (p < 0.05). The area under the receiver operating characteristic curve (83.9) was significantly greater than current ACNS models. We have developed a thoracoabdominal injury probability model that may improve patient triage when used with ACNS.

  1. Gas revenue increasingly significant

    International Nuclear Information System (INIS)

    Megill, R.E.

    1991-01-01

    This paper briefly describes the wellhead prices of natural gas compared to crude oil over the past 70 years. Although natural gas prices have never reached price parity with crude oil, the relative value of a gas BTU has been increasing. It is one of the reasons that the total amount of money coming from natural gas wells is becoming more significant. From 1920 to 1955 the revenue at the wellhead for natural gas was only about 10% of the money received by producers. Most of the money needed for exploration, development, and production came from crude oil. At present, however, over 40% of the money from the upstream portion of the petroleum industry is from natural gas. As a result, in a few short years natural gas may become 50% of the money revenues generated from wellhead production facilities

  2. Endocrine potency of wastewater: Contents of endocrine disrupting chemicals and effects measured by in vivo and in vitro assays

    DEFF Research Database (Denmark)

    Kusk, Kresten Ole; Krüger, Tanja; Long, Manhai

    2011-01-01

    chemical analysis and a battery of bioassays. Influent samples, collected at the first STP grate, and effluent samples, collected after the sewage treatment, were extracted using solid phase extraction. Extracts were analyzed for the content of a range of industrial chemicals with endocrine disrupting...... properties: phthalate metabolites, parabens, industrial phenols, ultraviolet screens, and natural and synthetic steroid estrogens. The endocrine disrupting bioactivity and toxicity of the extracts were analyzed in cell culture assay for the potency to affect the function of the estrogen, androgen, aryl......Industrial and municipal effluents are important sources of endocrine disrupting compounds (EDCs) discharged into the aquatic environment. This study investigated the endocrine potency of wastewater and the cleaning efficiency of two typical urban Danish sewage treatment plants (STPs), using...

  3. Vinblastine 20' Amides: Synthetic Analogues That Maintain or Improve Potency and Simultaneously Overcome Pgp-Derived Efflux and Resistance.

    Science.gov (United States)

    Lukesh, John C; Carney, Daniel W; Dong, Huijun; Cross, R Matthew; Shukla, Vyom; Duncan, Katharine K; Yang, Shouliang; Brody, Daniel M; Brütsch, Manuela M; Radakovic, Aleksandar; Boger, Dale L

    2017-09-14

    A series of 180 vinblastine 20' amides were prepared in three steps from commercially available starting materials, systematically exploring a typically inaccessible site in the molecule enlisting a powerful functionalization strategy. Clear structure-activity relationships and a structural model were developed in the studies which provided many such 20' amides that exhibit substantial and some even remarkable enhancements in potency, many that exhibit further improvements in activity against a Pgp overexpressing resistant cancer cell line, and an important subset of the vinblastine analogues that display little or no differential in activity against a matched pair of vinblastine sensitive and resistant (Pgp overexpressing) cell lines. The improvements in potency directly correlated with target tubulin binding affinity, and the reduction in differential functional activity against the sensitive and Pgp overexpressing resistant cell lines was found to correlate directly with an impact on Pgp-derived efflux.

  4. Derivation of an occupational exposure limit (OEL) for methylene chloride based on acute CNS effects and relative potency analysis.

    Science.gov (United States)

    Storm, J E; Rozman, K K

    1998-06-01

    The Occupational Safety and Health Administration (OSHA) methylene chloride Permissible Exposure Level (PEL) or 25 ppm is quantitatively derived from mouse tumor results observed in a high-exposure National Toxicology Program bioassay. Because this approach depends on controversial interspecies and low-dose extrapolations, the PEL itself has stimulated heated debate. Here, an alternative safety assessment for methylene chloride is presented. It is based on an acute human lowest-observed-adverse-effect level (LOAEL) of 200 ppm for subtle central nervous system (CNS) depression. Steep, parallel exposure-response curves for anesthetic and subanesthetic CNS effects associated with compounds mechanistically and structurally related to methylene chloride are shown to support a safety factor of two to account for inter-individual variability in response. LOAEL/no-observed-adverse-effect ratios for subtle CNS effects associated with structurally related solvents are shown to support a safety factor range of two to four to account for uncertainty in identifying a subthreshold exposure level. Anesthetic relative potencies and anesthetic/subanesthetic effect level ratios are shown to be constant for the compounds evaluated, demonstrating that subanesthetic relative potencies are also constant. Relative potencies among similarly derived occupational exposure limits (OELs) for solvents structurally related to methylene chloride are therefore used to validate the derived methylene chloride OEL range of 25-50 ppm. Because this safety assessment is based on human (rather than rodent) data and empirical (rather than theoretical) exposure-response relationships and is supported by relative potency analysis, it is a defensible alternative to to the OSHA risk assessment and should positively contribute to the debate regarding the appropriate basis and value for a methylene chloride PEL.

  5. Tumor significant dose

    International Nuclear Information System (INIS)

    Supe, S.J.; Nagalaxmi, K.V.; Meenakshi, L.

    1983-01-01

    In the practice of radiotherapy, various concepts like NSD, CRE, TDF, and BIR are being used to evaluate the biological effectiveness of the treatment schedules on the normal tissues. This has been accepted as the tolerance of the normal tissue is the limiting factor in the treatment of cancers. At present when various schedules are tried, attention is therefore paid to the biological damage of the normal tissues only and it is expected that the damage to the cancerous tissues would be extensive enough to control the cancer. Attempt is made in the present work to evaluate the concent of tumor significant dose (TSD) which will represent the damage to the cancerous tissue. Strandquist in the analysis of a large number of cases of squamous cell carcinoma found that for the 5 fraction/week treatment, the total dose required to bring about the same damage for the cancerous tissue is proportional to T/sup -0.22/, where T is the overall time over which the dose is delivered. Using this finding the TSD was defined as DxN/sup -p/xT/sup -q/, where D is the total dose, N the number of fractions, T the overall time p and q are the exponents to be suitably chosen. The values of p and q are adjusted such that p+q< or =0.24, and p varies from 0.0 to 0.24 and q varies from 0.0 to 0.22. Cases of cancer of cervix uteri treated between 1978 and 1980 in the V. N. Cancer Centre, Kuppuswamy Naidu Memorial Hospital, Coimbatore, India were analyzed on the basis of these formulations. These data, coupled with the clinical experience, were used for choice of a formula for the TSD. Further, the dose schedules used in the British Institute of Radiology fraction- ation studies were also used to propose that the tumor significant dose is represented by DxN/sup -0.18/xT/sup -0.06/

  6. Uranium chemistry: significant advances

    International Nuclear Information System (INIS)

    Mazzanti, M.

    2011-01-01

    The author reviews recent progress in uranium chemistry achieved in CEA laboratories. Like its neighbors in the Mendeleev chart uranium undergoes hydrolysis, oxidation and disproportionation reactions which make the chemistry of these species in water highly complex. The study of the chemistry of uranium in an anhydrous medium has led to correlate the structural and electronic differences observed in the interaction of uranium(III) and the lanthanides(III) with nitrogen or sulfur molecules and the effectiveness of these molecules in An(III)/Ln(III) separation via liquid-liquid extraction. Recent work on the redox reactivity of trivalent uranium U(III) in an organic medium with molecules such as water or an azide ion (N 3 - ) in stoichiometric quantities, led to extremely interesting uranium aggregates particular those involved in actinide migration in the environment or in aggregation problems in the fuel processing cycle. Another significant advance was the discovery of a compound containing the uranyl ion with a degree of oxidation (V) UO 2 + , obtained by oxidation of uranium(III). Recently chemists have succeeded in blocking the disproportionation reaction of uranyl(V) and in stabilizing polymetallic complexes of uranyl(V), opening the way to to a systematic study of the reactivity and the electronic and magnetic properties of uranyl(V) compounds. (A.C.)

  7. Meaning and significance of

    Directory of Open Access Journals (Sweden)

    Ph D Student Roman Mihaela

    2011-05-01

    Full Text Available The concept of "public accountability" is a challenge for political science as a new concept in this area in full debate and developement ,both in theory and practice. This paper is a theoretical approach of displaying some definitions, relevant meanings and significance odf the concept in political science. The importance of this concept is that although originally it was used as a tool to improve effectiveness and eficiency of public governance, it has gradually become a purpose it itself. "Accountability" has become an image of good governance first in the United States of America then in the European Union.Nevertheless,the concept is vaguely defined and provides ambiguous images of good governance.This paper begins with the presentation of some general meanings of the concept as they emerge from specialized dictionaries and ancyclopaedies and continues with the meanings developed in political science. The concept of "public accontability" is rooted in economics and management literature,becoming increasingly relevant in today's political science both in theory and discourse as well as in practice in formulating and evaluating public policies. A first conclusin that emerges from, the analysis of the evolution of this term is that it requires a conceptual clarification in political science. A clear definition will then enable an appropriate model of proving the system of public accountability in formulating and assessing public policies, in order to implement a system of assessment and monitoring thereof.

  8. Dual deep modeling: multi-level modeling with dual potencies and its formalization in F-Logic.

    Science.gov (United States)

    Neumayr, Bernd; Schuetz, Christoph G; Jeusfeld, Manfred A; Schrefl, Michael

    2018-01-01

    An enterprise database contains a global, integrated, and consistent representation of a company's data. Multi-level modeling facilitates the definition and maintenance of such an integrated conceptual data model in a dynamic environment of changing data requirements of diverse applications. Multi-level models transcend the traditional separation of class and object with clabjects as the central modeling primitive, which allows for a more flexible and natural representation of many real-world use cases. In deep instantiation, the number of instantiation levels of a clabject or property is indicated by a single potency. Dual deep modeling (DDM) differentiates between source potency and target potency of a property or association and supports the flexible instantiation and refinement of the property by statements connecting clabjects at different modeling levels. DDM comes with multiple generalization of clabjects, subsetting/specialization of properties, and multi-level cardinality constraints. Examples are presented using a UML-style notation for DDM together with UML class and object diagrams for the representation of two-level user views derived from the multi-level model. Syntax and semantics of DDM are formalized and implemented in F-Logic, supporting the modeler with integrity checks and rich query facilities.

  9. Establishment of an in vivo potency assay for the recombinant hepatit is B surface antigen in monovalent and combined vaccines

    Directory of Open Access Journals (Sweden)

    Mabel Izquierdo-López

    2014-12-01

    Full Text Available In this paper the development of potency assay in animals (mice was made, with the objective of demonstrating the immunogenic power of the recombinant Hepatitis B surface antigen in monovalent and combined vaccines, produced at the Center of Genetic Engineering and Biotechnology. The potency test is a parameter in quality control and it is also a tool to demonstrate the consistency of the production process. Parameters such as duration of the test, number of animals in the test, as well as different areas for the maintenance of the animals were evaluated. The results on the applicability of the potency test, to two presentations of the vaccines; monovalent Heberbiovac HB and pentavalent liquid in one vial Heberpenta-L are shown, for which specificity studies, evaluating different vaccine lots, the behavior of linearity, and parallelism, as well as establishing quality specification of the test were performed. This assay led to the obtainment of reliable results for the vaccines evaluated, the consistent evaluation of the immunogenic power and the monitoring of different production processes.

  10. Antimicrobial Peptide Potency is Facilitated by Greater Conformational Flexibility when Binding to Gram-negative Bacterial Inner Membranes

    Science.gov (United States)

    Amos, Sarah-Beth T. A.; Vermeer, Louic S.; Ferguson, Philip M.; Kozlowska, Justyna; Davy, Matthew; Bui, Tam T.; Drake, Alex F.; Lorenz, Christian D.; Mason, A. James

    2016-11-01

    The interaction of antimicrobial peptides (AMPs) with the inner membrane of Gram-negative bacteria is a key determinant of their abilities to exert diverse bactericidal effects. Here we present a molecular level understanding of the initial target membrane interaction for two cationic α-helical AMPs that share structural similarities but have a ten-fold difference in antibacterial potency towards Gram-negative bacteria. The binding and insertion from solution of pleurocidin or magainin 2 to membranes representing the inner membrane of Gram-negative bacteria, comprising a mixture of 128 anionic and 384 zwitterionic lipids, is monitored over 100 ns in all atom molecular dynamics simulations. The effects of the membrane interaction on both the peptide and lipid constituents are considered and compared with new and published experimental data obtained in the steady state. While both magainin 2 and pleurocidin are capable of disrupting bacterial membranes, the greater potency of pleurocidin is linked to its ability to penetrate within the bacterial cell. We show that pleurocidin displays much greater conformational flexibility when compared with magainin 2, resists self-association at the membrane surface and penetrates further into the hydrophobic core of the lipid bilayer. Conformational flexibility is therefore revealed as a key feature required of apparently α-helical cationic AMPs for enhanced antibacterial potency.

  11. Universal Survival Curve and Single Fraction Equivalent Dose: Useful Tools in Understanding Potency of Ablative Radiotherapy

    International Nuclear Information System (INIS)

    Park, Clint; Papiez, Lech; Zhang Shichuan; Story, Michael; Timmerman, Robert D.

    2008-01-01

    Purpose: Overprediction of the potency and toxicity of high-dose ablative radiotherapy such as stereotactic body radiotherapy (SBRT) by the linear quadratic (LQ) model led to many clinicians' hesitating to adopt this efficacious and well-tolerated therapeutic option. The aim of this study was to offer an alternative method of analyzing the effect of SBRT by constructing a universal survival curve (USC) that provides superior approximation of the experimentally measured survival curves in the ablative, high-dose range without losing the strengths of the LQ model around the shoulder. Methods and Materials: The USC was constructed by hybridizing two classic radiobiologic models: the LQ model and the multitarget model. We have assumed that the LQ model gives a good description for conventionally fractionated radiotherapy (CFRT) for the dose to the shoulder. For ablative doses beyond the shoulder, the survival curve is better described as a straight line as predicted by the multitarget model. The USC smoothly interpolates from a parabola predicted by the LQ model to the terminal asymptote of the multitarget model in the high-dose region. From the USC, we derived two equivalence functions, the biologically effective dose and the single fraction equivalent dose for both CFRT and SBRT. Results: The validity of the USC was tested by using previously published parameters of the LQ and multitarget models for non-small-cell lung cancer cell lines. A comparison of the goodness-of-fit of the LQ and USC models was made to a high-dose survival curve of the H460 non-small-cell lung cancer cell line. Conclusion: The USC can be used to compare the dose fractionation schemes of both CFRT and SBRT. The USC provides an empirically and a clinically well-justified rationale for SBRT while preserving the strengths of the LQ model for CFRT

  12. Analysis of Cannabis Seizures in NSW, Australia: Cannabis Potency and Cannabinoid Profile

    Science.gov (United States)

    Li, Kong M.; Arnold, Jonathon C.; McGregor, Iain S.

    2013-01-01

    Recent analysis of the cannabinoid content of cannabis plants suggests a shift towards use of high potency plant material with high levels of Δ9-tetrahydrocannabinol (THC) and low levels of other phytocannabinoids, particularly cannabidiol (CBD). Use of this type of cannabis is thought by some to predispose to greater adverse outcomes on mental health and fewer therapeutic benefits. Australia has one of the highest per capita rates of cannabis use in the world yet there has been no previous systematic analysis of the cannabis being used. In the present study we examined the cannabinoid content of 206 cannabis samples that had been confiscated by police from recreational users holding 15 g of cannabis or less, under the New South Wales “Cannabis Cautioning” scheme. A further 26 “Known Provenance” samples were analysed that had been seized by police from larger indoor or outdoor cultivation sites rather than from street level users. An HPLC method was used to determine the content of 9 cannabinoids: THC, CBD, cannabigerol (CBG), and their plant-based carboxylic acid precursors THC-A, CBD-A and CBG-A, as well as cannabichromene (CBC), cannabinol (CBN) and tetrahydrocannabivarin (THC-V). The “Cannabis Cautioning” samples showed high mean THC content (THC+THC-A = 14.88%) and low mean CBD content (CBD+CBD-A = 0.14%). A modest level of CBG was detected (CBG+CBG-A = 1.18%) and very low levels of CBC, CBN and THC-V (cannabis with very low CBD content. The implications for public health outcomes and harm reduction strategies are discussed. PMID:23894589

  13. Chemical composition and antimicrobial potency of essential oils from roots of Pinus growing in Algeria

    Directory of Open Access Journals (Sweden)

    Nadia FEKIH

    2016-11-01

    Full Text Available The objective of this study is to determine the chemical composition and antimicrobial potency of essential oils of three roots of genus Pinus (P. halepensis, P. pinea and P. pinaster growing in Algeria for the first time. The essential oils used in the present study were isolated by hydrodistillation using a Cleavenger-type apparatus according the European Pharmacopoeia, and identified by GC and GC-MS. 14, 12, 11 constituents were identified, representing an average of 98.8 %, 91.3 % and 83.6 % of the total oil of roots of P. halepensis, P. pinea and P. pinaster respectively. The chemical profile reveals the dominance of monoterpenes compounds, although some quantitative variance was noticed. The main constituents of the oil root of P. halepensis were α-Pinene (87.4 % and trans-p-Caryophyllene (3.5 %. The oil of P. pinea was dominated by Limonene (66.3 %, Trans-p-Caryophyllene (9.6 %, Myrcene (3.2 % and Osmorhizol (3.2 %. The oil of P. pinaster was rich by α-Pinene (22 %, β-Pinene (27.1 % and Trans-p-Caryophyllene (21.4 %. The antimicrobial activities of the essential oils from roots of P. halepensis, P. pinea and P. pinaster were tested against a panel of bacteria and one yeast strain using the agar well diffusion technique and dilution methods. The diameters of zones of inhibition exhibited by the essential oils were between 7 and 25 mm. The minimal inhibitory concentration was 28.4 μg/mL of P. halepensis and P. pinaster against S. aureus and C. albicans respectively.

  14. Stat5 phosphorylation is responsible for the excessive potency of HB-EGF.

    Science.gov (United States)

    Heo, Jeongyeon; Kim, Jae Geun; Kim, Sunghwan; Kang, Hara

    2017-12-23

    Heparin-binding EGF-like growth factor (HB-EGF) is a potent growth factor involved in wound healing and tumorigenesis. Despite the sequence similarity between HB-EGF and EGF, HB-EGF induces cellular proliferation and migration more potently than EGF. However, the differential regulation by HB-EGF and EGF has not been thoroughly elucidated. In this study, we compared signaling pathways activated by HB-EGF and EGF to understand the details of the molecular mechanism of the high potency induced by HB-EGF. HB-EGF specifically induced the phosphorylation of EGFR-Y1045 and activated Stat5, which is responsible for promoting cell proliferation, and migration. The competition of phosphorylated EGFR-Y1045 inhibited Stat5 activation and consequently lowered the effect of HB-EGF on cell proliferation, suggesting that the phosphorylation of EGFR-Y1045 is essential for the activation of Stat5. The phosphorylation of EGFR-Y1045 and Stat5 induced by HB-EGF was prevented by sequestering the heparin-binding domain, suggesting that the heparin-binding domain is critical for HB-EGF-mediated signaling and cellular responses. In conclusion, the heparin-binding domain of HB-EGF was responsible for EGFR-mediated Stat5 activation, resulting in a more potent cellular proliferation, and migration than that mediated by EGF. This molecular mechanism is useful for understanding ligand-specific EGFR signaling and developing biomedicines for wound healing or cancer therapy. © 2017 Wiley Periodicals, Inc.

  15. Differential Potency of 2,6-Dimethylcyclohexanol Isomers for Positive Modulation of GABAA Receptor Currents.

    Science.gov (United States)

    Chowdhury, Luvana; Croft, Celine J; Goel, Shikha; Zaman, Naina; Tai, Angela C-S; Walch, Erin M; Smith, Kelly; Page, Alexandra; Shea, Kevin M; Hall, C Dennis; Jishkariani, D; Pillai, Girinath G; Hall, Adam C

    2016-06-01

    GABAA receptors meet all of the pharmacological requirements necessary to be considered important targets for the action of general anesthetic agents in the mammalian brain. In the following patch-clamp study, the relative modulatory effects of 2,6-dimethylcyclohexanol diastereomers were investigated on human GABAA (α1β3γ2s) receptor currents stably expressed in human embryonic kidney cells. Cis,cis-, trans,trans-, and cis,trans-isomers were isolated from commercially available 2,6-dimethylcyclohexanol and were tested for positive modulation of submaximal GABA responses. For example, the addition of 30 μM cis,cis-isomer resulted in an approximately 2- to 3-fold enhancement of the EC20 GABA current. Coapplications of 30 μM 2,6-dimethylcyclohexanol isomers produced a range of positive enhancements of control GABA responses with a rank order for positive modulation: cis,cis > trans,trans ≥ mixture of isomers > > cis,trans-isomer. In molecular modeling studies, the three cyclohexanol isomers bound with the highest binding energies to a pocket within transmembrane helices M1 and M2 of the β3 subunit through hydrogen-bonding interactions with a glutamine at the 224 position and a tyrosine at the 220 position. The energies for binding to and hydrogen-bond lengths within this pocket corresponded with the relative potencies of the agents for positive modulation of GABAA receptor currents (cis,cis > trans,trans > cis,trans-2,6-dimethylcyclohexanol). In conclusion, the stereochemical configuration within the dimethylcyclohexanols is an important molecular feature in conferring positive modulation of GABAA receptor activity and for binding to the receptor, a consideration that needs to be taken into account when designing novel anesthetics with enhanced therapeutic indices. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  16. Significant Radionuclides Determination

    Energy Technology Data Exchange (ETDEWEB)

    Jo A. Ziegler

    2001-07-31

    The purpose of this calculation is to identify radionuclides that are significant to offsite doses from potential preclosure events for spent nuclear fuel (SNF) and high-level radioactive waste expected to be received at the potential Monitored Geologic Repository (MGR). In this calculation, high-level radioactive waste is included in references to DOE SNF. A previous document, ''DOE SNF DBE Offsite Dose Calculations'' (CRWMS M&O 1999b), calculated the source terms and offsite doses for Department of Energy (DOE) and Naval SNF for use in design basis event analyses. This calculation reproduces only DOE SNF work (i.e., no naval SNF work is included in this calculation) created in ''DOE SNF DBE Offsite Dose Calculations'' and expands the calculation to include DOE SNF expected to produce a high dose consequence (even though the quantity of the SNF is expected to be small) and SNF owned by commercial nuclear power producers. The calculation does not address any specific off-normal/DBE event scenarios for receiving, handling, or packaging of SNF. The results of this calculation are developed for comparative analysis to establish the important radionuclides and do not represent the final source terms to be used for license application. This calculation will be used as input to preclosure safety analyses and is performed in accordance with procedure AP-3.12Q, ''Calculations'', and is subject to the requirements of DOE/RW-0333P, ''Quality Assurance Requirements and Description'' (DOE 2000) as determined by the activity evaluation contained in ''Technical Work Plan for: Preclosure Safety Analysis, TWP-MGR-SE-000010'' (CRWMS M&O 2000b) in accordance with procedure AP-2.21Q, ''Quality Determinations and Planning for Scientific, Engineering, and Regulatory Compliance Activities''.

  17. Disruptive Technologies in Higher Education

    Science.gov (United States)

    Flavin, Michael

    2012-01-01

    This paper analyses the role of "disruptive" innovative technologies in higher education. In this country and elsewhere, Higher Education Institutions (HEIs) have invested significant sums in learning technologies, with Virtual Learning Environments (VLEs) being more or less universal, but these technologies have not been universally…

  18. Chromogenic assay for BAY 81-8973 potency assignment has no impact on clinical outcome or monitoring in patient samples.

    Science.gov (United States)

    Kitchen, S; Katterle, Y; Beckmann, H; Maas Enriquez, M

    2016-06-01

    Essentials Discrepancies can exist in factor VIII activity measured by the one-stage or chromogenic assays. LEOPOLD trial data were used to assess clinical impact of BAY 81-8973 potency assignment assay. Efficacy was not affected by the assay used for potency assignment and dosing of BAY 81-8973. Either assay may be used to measure factor VIII activity after BAY 81-8973 infusion. Background Product-specific discrepancies have been reported for factor VIII (FVIII) activity determined with one-stage or chromogenic assays. Objective To assess the clinical impact of potency assignment of BAY 81-8973, a full-length, unmodified, recombinant human FVIII, by use of the chromogenic assay or chromogenic assay adjusted to mimic results obtained with the one-stage assay Patients/methods Patients aged 12-65 years with severe hemophilia A received BAY 81-8973 in LEOPOLD I (20-50 IU kg(-1) two or three times weekly [investigator decision]) and LEOPOLD II (randomized to 20-30 IU kg(-1) twice weekly, 30-40 IU kg(-1) three times weekly, or on-demand treatment). Both trials included two 6-month crossover periods in which potency labeling was determined with the chromogenic substrate assay as per the European Pharmacopoeia (CS/EP) or the chromogenic substrate assay adjusted to mimic results obtained with the one-stage assay (CS/ADJ). The annualized bleeding rate (ABR) and FVIII incremental recovery were assessed by the use of pooled data. Results The analysis was perfomed on 121 patients. Median (quartile [Q] 1; Q3) ABRs during the CS/EP and CS/ADJ periods were 1.98 (0; 5.92) and 1.98 (0; 7.34), respectively. The mean incremental recovery was > 2 IU dL(-1) per IU kg(-1) in both periods with the use of either assay for postinfusion FVIII measurements. The median (Q1; Q3) chromogenic/one-stage assay recovery ratio was 1.054 (0.892; 1.150) for the CS/EP period when a plasma standard was used for calibration. Conclusions No impact on the ABR was observed with chromogenic-based as compared

  19. Just say 'know': how do cannabinoid concentrations influence users' estimates of cannabis potency and the amount they roll in joints?

    Science.gov (United States)

    Freeman, Tom P; Morgan, Celia J A; Hindocha, Chandni; Schafer, Gráinne; Das, Ravi K; Curran, H Valerie

    2014-10-01

    (1) To determine whether measured concentrations of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in individuals' own cannabis predict their estimates of drug potency and actual titration; and (2) to ascertain if these effects are influenced by frequency of use and cannabis type. Cross-sectional, naturalistic. Participants' own homes. A total of 247 cannabis users in the United Kingdom: 152 'recreational' (1-24 days/month) and 95 'daily' (≥25 days/month). Participants rated their own cannabis for its potency (1-10) and type ('resin', 'herbal', 'skunk') before smoking it in front of the researcher. The amount of cannabis (g) used in their joints was recorded and an additional sample was analysed for THC and CBD concentrations (%). THC concentrations were related negatively to the amount of cannabis used [unstandardized regression coefficient: b = -0.009, 95% confidence interval (CI) = -0.017, -0.002]. Potency estimates were predicted by increasing THC (b = 0.055, 95% CI = 0.020, 0.090) and decreasing CBD (b = -0.160, 95% CI = -0.284, -0.062), and both of these associations were mediated by cannabis type (THC: b = 0.018, 95% CI = 0.006, 0.037; CBD: b = -0.105, 95% CI = -0.198, -0.028). Potency estimates were more reflective of THC as frequency of use increased (b = 0.004, 95% CI = 0.001, 0.007) and were 7.3 times more so in daily (partial r = 0.381) than recreational users (r = 0.052). When using their own cannabis in a naturalistic setting, people titrate the amount they roll in joints according to concentrations of delta-9-tetrahydrocannabinol (THC) but not cannabidiol (CBD). Recreational users thus show poor understanding of cannabis potency. © 2014 Society for the Study of Addiction.

  20. Myocardial potency of Bio-tea against Isoproterenol induced myocardial damage in rats.

    Science.gov (United States)

    Lobo, Reema Orison; Shenoy, Chandrakala K

    2015-07-01

    Kombucha (Bio-tea) is a beverage produced by the fermentation of sugared black tea using a symbiotic association of bacteria and yeasts. Traditional claims about Kombucha report beneficial effects such as antibiotic properties, gastric regulation, relief from joint rheumatism and positive influence on the cholesterol level, arteriosclerosis, diabetes, and aging problems. The present investigation was carried out to understand the preventive effect of Kombucha on heart weight, blood glucose, total protein, lipid profile and cardiac markers in rats with myocardial damage induced using Isoproterenol. As Bio-tea is produced by fermenting tea, the parameters were compared in rats pre-treated with normal black tea and Bio-tea for 30 days followed by subcutaneous injection of Isoproterenol (85 mg/kg body weight). Normal rats as well as Isoproterenol induced myocardial infarcted rats were also used, which served as controls. Isoproterenol induced myocardial infarcted control rats showed a significant increase in heart weight, blood glucose and cardiac markers and a decrease in plasma protein. Increased levels of cholesterol, triglycerides, low density lipids (LDL) and very low density lipids (VLDL) were also observed, while the high density lipid (HDL) content decreased. Bio-tea showed a higher preventive effect against myocardial infarction when compared to tea, as was observed by the significant reduction in heart weight, and blood glucose and increase in plasma albumin levels. Bio-tea significantly decreased cholesterol, triglycerides, LDL and VLDL while simultaneously increasing the levels of HDL. Similarly a decrease in leakage of cardiac markers from the myocardium was also observed.

  1. Towards higher intensities

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    Over the past 2 weeks, commissioning of the machine protection system has advanced significantly, opening up the possibility of higher intensity collisions at 3.5 TeV. The intensity has been increased from 2 bunches of 1010 protons to 6 bunches of 2x1010 protons. Luminosities of 6x1028 cm-2s-1 have been achieved at the start of fills, a factor of 60 higher than those provided for the first collisions on 30 March.   The recent increase in LHC luminosity as recorded by the experiments. (Graph courtesy of the experiments and M. Ferro-Luzzi) To increase the luminosity further, the commissioning crews are now trying to push up the intensity of the individual proton bunches. After the successful injection of nominal intensity bunches containing 1.1x1011 protons, collisions were subsequently achieved at 450 GeV with these intensities. However, half-way through the first ramping of these nominal intensity bunches to 3.5 TeV on 15 May, a beam instability was observed, leading to partial beam loss...

  2. 10−7 m 17β-oestradiol enhances odonto/osteogenic potency of human dental pulp stem cells by activation of the NF-κB pathway

    Science.gov (United States)

    Wang, Y; Zheng, Y; Wang, Z; Li, J; Wang, Z; Zhang, G; Yu, J

    2013-01-01

    Objectives Oestrogen has been proven to significantly enhance osteogenic potency, while oestrogen deficiency usually leads to impaired osteogenic differentiation of mesenchymal stem cells. However, little is known concerning direct effects of oestrogen on differentiation of human dental pulp stem cells (DPSCs). Materials and methods In this study, human DPSCs were isolated and treated with 10−7 m 17β-oestradiol (E2). Alkaline phosphatase (ALP) assay and alizarin red staining were performed. Results Alkaline phosphatase and alizarin red showed that E2 treatment significantly enhanced ALP activity and mineralization ability of DPSCs, but had no effect on cell proliferation. Real-time RT-PCR and western blot assay demonstrated that odonto/osteogenic markers (ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN and DSPP/DSP) were significantly upregulated in the cells after E2 treatment. Moreover, phosphorylation of cytoplasmic IκBα/P65 and expression of nuclear P65 were enhanced in a time-dependent manner following E2 treatment, suggesting activation of NF-κB signaling. Conversely, inhibition of the NF-κB pathway suppressed E2-mediated upregulation of odonto/osteogenic markers, indicating that the NF-κB pathway was pivotal for E2-mediated differentiation. Conclusion These findings provide evidence that 10−7 m 17β-oestradiol promoted odonto/osteogenic differentiation of human DPSCs via activation of the NF-κB signaling pathway. PMID:24152244

  3. Andrographolide sodium bisulphite-induced inactivation of urease: inhibitory potency, kinetics and mechanism.

    Science.gov (United States)

    Mo, Zhi-Zhun; Wang, Xiu-Fen; Zhang, Xie; Su, Ji-Yan; Chen, Hai-Ming; Liu, Yu-Hong; Zhang, Zhen-Biao; Xie, Jian-Hui; Su, Zi-Ren

    2015-07-16

    The inhibitory effect of andrographolide sodium bisulphite (ASB) on jack bean urease (JBU) and Helicobacter pylori urease (HPU) was performed to elucidate the inhibitory potency, kinetics and mechanism of inhibition in 20 mM phosphate buffer, pH 7.0, 2 mM EDTA, 25 °C. The ammonia formations, indicator of urease activity, were examined using modified spectrophotometric Berthelot (phenol-hypochlorite) method. The inhibitory effect of ASB was characterized with IC50 values. Lineweaver-Burk and Dixon plots for JBU inhibition of ASB was constructed from the kinetic data. SH-blocking reagents and competitive active site Ni2+ binding inhibitors were employed for mechanism study. Molecular docking technique was used to provide some information on binding conformations as well as confirm the inhibition mode. The IC50 of ASB against JBU and HPU was 3.28±0.13 mM and 3.17±0.34 mM, respectively. The inhibition proved to be competitive and concentration- dependent in a slow-binding progress. The rapid formation of initial ASB-JBU complex with an inhibition constant of Ki=2.86×10(-3) mM was followed by a slow isomerization into the final complex with an overall inhibition constant of Ki*=1.33×10(-4) mM. The protective experiment proved that the urease active site is involved in the binding of ASB. Thiol reagents (L-cysteine and dithiothreithol) strongly protect the enzyme from the loss of enzymatic activity, while boric acid and fluoride show weaker protection, indicating that the active-site sulfhydryl group of JBU was potentially involved in the blocking process. Moreover, inhibition of ASB proved to be reversible since ASB-inactivated JBU could be reactivated by dithiothreitol application. Molecular docking assay suggested that ASB made contacts with the important sulfhydryl group Cys-592 residue and restricted the mobility of the active-site flap. ASB was a competitive inhibitor targeting thiol groups of urease in a slow-binding manner both reversibly and concentration

  4. Antibacterial potency of V.A.C. GranuFoam Silver(®) Dressing.

    Science.gov (United States)

    Sachsenmaier, Saskia; Peschel, Andreas; Ipach, Ingmar; Kluba, Torsten

    2013-10-01

    V.A.C.(®) GranuFoam™ therapy is regularly used in the surgical therapy of infected wounds and soft tissue injuries. Silver nanoparticles can destroy bacterial cell walls and inhibit enzymes for cell replication. Silver dressings are therefore successfully used for many indications in wound therapy. In this study, we investigated the antimicrobial potency of ionic silver released from the silver-coated V.A.C.(®) GranuFoam™ during vacuum therapy. Silver dressing was exposed to agar plates populated with bacteria to measure silver release. A total of 15 agar plates colonised with either Staphylococcus aureus populations or with Staphylococcus epidermidis, were loaded with V.A.C. GranuFoam Silver(®) Dressing polyurethane foam (KCI, San Antonio, Texas). Each of 13 pieces of silver-coated foam was applied to an agar plate. Two plates were loaded with conventional black foam without any coating. After connecting to a vacuum pump, the vacuum therapy of the 15 plates lasted 5 days. The zone of inhibition of bacterial growth around the foam was measured daily. Silver release was also determined as a function of time. At each time point, there was evidence of silver in the agar independent of bacterial colonisation. The S. aureus agar showed a consecutive increase in silver concentration from baseline upon 48 h after exposure to the negative pressure of V.A.C. therapy. An increasing mean silver level after 48, 72 and 96 h was measured under V.A.C. therapy with a peak value after 120 h. In contrast, the results from the S. epidermidis plates did not follow a linear pattern. At the beginning of vacuum therapy, we documented a rise in silver concentration. After 48-96h, the silver levels fluctuated. A maximum zone of inhibition in both bacterial colonised plates (S. aureus and S. epidermidis) was found 39 h after the start of the V.A.C. GranuFoam Silver(®) therapy. From our results, we confirmed the antimicrobial effect of the silver ions against S. aureus and S

  5. In vitro versus in vivo concordance: a case study of the replacement of an animal potency test with an immunochemical assay.

    Science.gov (United States)

    Schofield, T

    2002-01-01

    Early in its development, the potency of Merck's recombinant hepatitis B vaccine, RECOMBIVAX HB, was monitored using an assay performed in mice. A specification was determined to be the lowest potency which induced acceptable response in clinical trials. As a post-licensing commitment, Merck was asked to replace its mouse potency assay with an in vitro procedure for product release in the US market. Early studies with a commercial enzyme immunoassay (EIA) yielded highly variable results. That assay, combined with a sample pretreatment step, proved more dependable and predictive of potency in the mouse assay. Based on measurements made on manufactured materials, combined with experiments contrived to yield a wide range of reactivity in the two assays, concordance was established between the EIA and the mouse potency assay. This concordance was used to calibrate a specification for the in vitro assay that is predictive of a satisfactory response in vivo. Data from clinical trials established a correspondence between human immunogenicity and these potency markers.

  6. A Retrospective Cohort Study of the Potency of lipid-lowering therapy and Race-gender Differences in LDL cholesterol control

    Directory of Open Access Journals (Sweden)

    Weiner Mark

    2011-09-01

    Full Text Available Abstract Background Reasons for race and gender differences in controlling elevated low density lipoprotein (LDL cholesterol may be related to variations in prescribed lipid-lowering therapy. We examined the effect of lipid-lowering drug treatment and potency on time until LDL control for black and white women and men with a baseline elevated LDL. Methods We studied 3,484 older hypertensive patients with dyslipidemia in 6 primary care practices over a 4-year timeframe. Potency of lipid-lowering drugs calculated for each treated day and summed to assess total potency for at least 6 and up to 24 months. Cox models of time to LDL control within two years and logistic regression models of control within 6 months by race-gender adjust for: demographics, clinical, health care delivery, primary/specialty care, LDL measurement, and drug potency. Results Time to LDL control decreased as lipid-lowering drug potency increased (P Conclusions Black women and, to a lesser extent, black men and white women were less likely to achieve LDL control than white men after accounting for lipid-lowering drug potency as well as diverse patient and provider factors. Future work should focus on the contributions of medication adherence and response to treatment to these clinically important differences.

  7. The local lymph node assay compared with the human maximization test as an indicator of allergic potency in humans using patch test clinic populations.

    Science.gov (United States)

    Zaghi, Danny; Maibach, Howard I

    2009-01-01

    The human maximization test (HMT) is a method to evaluate potency in humans, while the local lymph node assay (LLNA) is a test method that allows for the measuring of the allergic potency of a substance in a rodent. It has been proposed that an EC3 value (the value obtained by the LLNA test, ie, the concentration of an allergen leading to a 3-fold increase of baseline proliferation rate) would be a reliable indicator for a compound's allergic potency in humans. This paper compares the correlation between the EC3 value of a compound and its allergic occurrence in the general population with the correlation between the HMT of the compound and its allergic occurrence in the general population, to determine the relationship to potency. The correlation values when outliers were removed from the sample were -0.56 and -0.71 for LLNA and HMT, respectively, suggesting that there is a possible 20% error margin in LLNA's ability to predict potency. The data also suggest that other factors (such as exposure) could play up to a 30% role in the determination of allergic occurrence in the general population. The potency assays might be made more clinically relevant for predicting allergic frequencies by including a frequency factor and other factors in its dermatotoxicological interpretation.

  8. Measurement of micronuclei and internal dose in mice demonstrates that 3-monochloropropane-1,2-diol (3-MCPD) has no genotoxic potency in vivo.

    Science.gov (United States)

    Aasa, Jenny; Törnqvist, Margareta; Abramsson-Zetterberg, Lilianne

    2017-11-01

    In this study 3-monochloropropane-1,2-diol (3-MCPD), a compound that appears as contaminant in refined cooking oils, has been studied with regard to genotoxicity in vivo (mice) with simultaneous measurement of internal dose using state-of-the-art methodologies. Genotoxicity (chromosomal aberrations) was measured by flow cytometry with dual lasers as the frequency of micronuclei in erythrocytes in peripheral blood from BalbC mice intraperitoneally exposed to 3-MCPD (0, 50, 75, 100, 125 mg/kg). The internal doses of 3-MCPD in the mice were calculated from N-(2,3-dihydroxypropyl)-valine adducts to hemoglobin (Hb), quantified at very low levels by high-resolution mass spectrometry. Convincing evidence for absence of genotoxic potency in correlation to measured internal doses in the mice was demonstrated, despite relatively high administered doses of 3-MCPD. The results are discussed in relation to another food contaminant that is formed as ester in parallel to 3-MCPD esters in oil processing, i.e. glycidol, which has been studied previously by us in a similar experimental setup. Glycidol has been shown to be genotoxic, and in addition to have ca. 1000 times higher rate of adduct formation compared to that observed for 3-MCPD. The conclusion is that at simultaneous exposure to 3-MCPD and glycidol the concern about genotoxicity would be glycidol. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Point mutation of a conserved aspartate, D69, in the muscarinic M2 receptor does not modify voltage-sensitive agonist potency.

    Science.gov (United States)

    Ågren, Richard; Sahlholm, Kristoffer; Nilsson, Johanna; Århem, Peter

    2018-01-29

    The muscarinic M 2 receptor (M 2 R) has been shown to display voltage-sensitive agonist binding, based on G protein-activated inward rectifier potassium channel (GIRK) opening and radioligand binding at different membrane voltages. A conserved aspartate in transmembrane segment (TM) II of M 2 R, D69, has been proposed as the voltage sensor. While a recent paper instead presented evidence of tyrosines in TMs III, VI, and VII acting as voltage sensors, these authors were not able to record GIRK channel activation by a D69N mutant M 2 R. In the present study, we succeeded in recording ACh-induced GIRK channel activation by this mutant at -80 and 0 mV. The acetylcholine EC 50 was about 2.5-fold higher at 0 mV, a potency shift very similar to that observed at wild-type M 2 R, indicating that voltage sensitivity persists at the D69N mutant. Thus, our present observations corroborate the notion that D69 is not responsible for voltage sensitivity of the M 2 R. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Strategies to generate high-titer, high-potency recombinant AAV3 serotype vectors

    Directory of Open Access Journals (Sweden)

    Chen Ling

    2016-01-01

    Full Text Available Although recombinant adeno-associated virus serotype 3 (AAV3 vectors were largely ignored previously, owing to their poor transduction efficiency in most cells and tissues examined, our initial observation of the selective tropism of AAV3 serotype vectors for human liver cancer cell lines and primary human hepatocytes has led to renewed interest in this serotype. AAV3 vectors and their variants have recently proven to be extremely efficient in targeting human and nonhuman primate hepatocytes in vitro as well as in vivo. In the present studies, we wished to evaluate the relative contributions of the cis-acting inverted terminal repeats (ITRs from AAV3 (ITR3, as well as the trans-acting Rep proteins from AAV3 (Rep3 in the AAV3 vector production and transduction. To this end, we utilized two helper plasmids: pAAVr2c3, which carries rep2 and cap3 genes, and pAAVr3c3, which carries rep3 and cap3 genes. The combined use of AAV3 ITRs, AAV3 Rep proteins, and AAV3 capsids led to the production of recombinant vectors, AAV3-Rep3/ITR3, with up to approximately two to fourfold higher titers than AAV3-Rep2/ITR2 vectors produced using AAV2 ITRs, AAV2 Rep proteins, and AAV3 capsids. We also observed that the transduction efficiency of Rep3/ITR3 AAV3 vectors was approximately fourfold higher than that of Rep2/ITR2 AAV3 vectors in human hepatocellular carcinoma cell lines in vitro. The transduction efficiency of Rep3/ITR3 vectors was increased by ∼10-fold, when AAV3 capsids containing mutations in two surface-exposed residues (serine 663 and threonine 492 were used to generate a S663V+T492V double-mutant AAV3 vector. The Rep3/ITR3 AAV3 vectors also transduced human liver tumors in vivo approximately twofold more efficiently than those generated with Rep2/ITR2. Our data suggest that the transduction efficiency of AAV3 vectors can be significantly improved both using homologous Rep proteins and ITRs as well as by capsid optimization. Thus, the combined use of

  11. EVALUATION OF POTENCY OF MUMPS VACCINE USED IN IRAN: COMPARISON OF WHO AND NIBSC METHOD IN CELL CULTURE

    Directory of Open Access Journals (Sweden)

    S. Tavajohi

    2005-06-01

    Full Text Available Vaccination against mumps is included in world Health Organization (WHO program of global immunization. Safety and efficacy of vaccines must be confirmed by control units in charge of public health. In Iran, the secondary control on potency of vaccine has not been set up yet. We decided to overcome this problem by developing WHO and NIBSC methods in Food and Drug Control Lab. ‎Nine dilutions of vaccine from 10-1 to 10-5 in ‎0.5log10 steps were mixed with Vero cell suspension. In WHO method, the cell suspension was seeded in octaplicate (8 wells of each dilution in 24-well plate and incubated at 36°C for 10 days, during which the cells were checked for cytopathic changes everyday and positive wells were recorded. We used 5% serum and 1 × 105 cells for the assays. The test was repeated with six different vaccines produced in one batch. The mean potency was 10 4.475±0.134 CCID50/vial for each ten-dose vial. For NIBSC method the dilutions of vaccine were added to hexaplicate (6 well per dilution in 24-wells plate. After 3 hours, the medium was removed and overlay was added. Then the plates were incubated at 35°C for 10 days. After incubation period, the plaques were stained with methyl violet and counted. This assay was repeated three times and the mean of results was 5.93 log10 PFU/dose. ‎ Results indicate that the potency of the vaccine is in acceptable range in either method. WHO method is simple and less time consuming compared to NIBSC method.

  12. Development and validation of a quantitative competitive ELISA for potency testing of equine anti rabies sera with other potential use.

    Science.gov (United States)

    Korimbocus, Jehanara; Dehay, Nicolas; Tordo, Noël; Cano, François; Morgeaux, Sylvie

    2016-06-14

    In case of a bite by a rabies infected animal, the World Health Organisation recommends a prophylactic treatment including the administration of Human Rabies Immunoglobulins (HRIGs) or highly purified F(ab')2 fragments produced from Equine Rabies Immunoglobulin (F(ab')2 - ERIGs). According to international regulation, quality control of F(ab')2 - ERIGs lots requires potency testing by the in vivo Mouse Neutralisation Test (MNT) prior marketing. However, the strategy of the 3Rs (Reduce, Refine, Replace) for animal testing required by the European Directive encourages the replacement of the in vivo potency test by an in vitro assay. In this context, a competitive ELISA method (c-ELISA) has been developed by the Agence Nationale de Sécurité du Médicament et des Produits de Santé where F(ab')2 - ERIGs are in competition with a monoclonal antibody recognizing the trimeric native form of the rabies glycoprotein. After a full validation study, the c-ELISA has been applied to commercial batches of F(ab')2 - ERIGs. A correlation study with the MNT demonstrated a similarity between the two methods (r=0.751). Moreover, the c-ELISA method which does not need any species specific reagent has been applied to HRIGs potency testing as an alternative method to Rapid Fluorescent Focus Inhibition Test (RFFIT), thus avoiding the handling of live rabies virus in BSL3 containment. In conclusion, the c-ELISA has shown its potential to replace MNT and possibly RFFIT for the quantification of rabies immunoglobulin. After optimisation it may be used for the quantification of rabies immunoglobulin in any animal species, notably for rabies immunogenicity assay in mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Interim relative potency factors for the toxicological risk assessment of pyrrolizidine alkaloids in food and herbal medicines.

    Science.gov (United States)

    Merz, Karl-Heinz; Schrenk, Dieter

    2016-11-30

    Pyrrolizidine alkaloids (PAs) are among the most potent natural toxins occurring in a broad spectrum of plant species from various families. Recently, findings of considerable contamination of teas/herbal infusions prepared from non-PA plants have been reported. These are obviously due to cross-contamination with minor amounts of PA plants and can affect both food and herbal medicines. Another source of human exposure is honey collected from PA plants. These findings illustrate the requirement for a comprehensive risk assessment of PAs, hampered by the enormous number of different PA congeners occurring in nature. Up to now, risk assessment is based on the carcinogenicity of certain PAs after chronic application to rats using the sum of detected PAs as dose metric. Because of the well-documented large structure-dependent differences between sub-groups of PA congeners with respect to their genotoxicity and (cyto)toxicity, however, this procedure is inadequate. Here we provide an overview of recent attempts to assess the risk of PA exposure and the available literature on the toxic effects and potencies of different congeners. Based on these considerations, we have derived interim Relative Potency (REP) factors for a number of abundant PAs suggesting a factor of 1.0 for cyclic di-esters and open-chain di-esters with 7S configuration, of 0.3 for mono-esters with 7S configuration, of 0.1 for open-chain di-esters with 7R configuration and of 0.01 for mono-esters with 7R configuration. For N-oxides we suggest to apply the REP factor of the corresponding PA. We are confident that the use of these values can provide a more scientific basis for PA risk assessment until a more detailed experimental analysis of the potencies of all relevant congeners can be carried out. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. In silico modelling of permeation enhancement potency in Caco-2 monolayers based on molecular descriptors and random forest

    DEFF Research Database (Denmark)

    Welling, Søren Havelund; Clemmensen, Line Katrine Harder; Buckley, Stephen T.

    2015-01-01

    has been developed.The random forest-QSAR model was based upon Caco-2 data for 41 surfactant-like permeation enhancers from Whitehead et al. (2008) and molecular descriptors calculated from their structure.The QSAR model was validated by two test-sets: (i) an eleven compound experimental set with Caco......-2 data and (ii) nine compounds with Caco-2 data from literature. Feature contributions, a recent developed diagnostic tool, was applied to elucidate the contribution of individual molecular descriptors to the predicted potency. Feature contributions provided easy interpretable suggestions...

  15. Adenine Nucleotide Analogues Locked in a Northern Methanocarba Conformation: Enhanced Stability and Potency as P2Y1 Receptor Agonists

    Science.gov (United States)

    Ravi, R. Gnana; Kim, Hak Sung; Servos, Jörg; Zimmermann, Herbert; Lee, Kyeong; Maddileti, Savitri; Boyer, José L.; Harden, T. Kendall; Jacobson, Kenneth A.

    2016-01-01

    Preference for the Northern (N) ring conformation of the ribose moiety of nucleotide 5′-triphosphate agonists at P2Y1, P2Y2, P2Y4, and P2Y11 receptors, but not P2Y6 receptors, was established using a ring-constrained methanocarba (a 3.1.0-bicyclohexane) ring as a ribose substitute (Kim et al. J. Med. Chem. 2002, 45, 208–218.). We have now combined the ring-constrained (N)-methanocarba modification of adenine nucleotides with other functionalities known to enhance potency at P2 receptors. The potency of the newly synthesized analogues was determined in the stimulation of phospholipase C through activation of turkey erythrocyte P2Y1 or human P2Y1 and P2Y2 receptors stably expressed in astrocytoma cells. An (N)-methanocarba-2-methylthio-ADP analogue displayed an EC50 at the hP2Y1 receptor of 0.40 nM and was 55-fold more potent than the corresponding triphosphate and 16-fold more potent than the riboside 5′-diphosphate. 2-Cl–(N)-methanocarba-ATP and its N6-Me analogue were also highly selective, full agonists at P2Y1 receptors. The (N)-methanocarba-2-methylthio and 2-chloromonophosphate analogues were full agonists exhibiting micromolar potency at P2Y1 receptors, while the corresponding ribosides were inactive. Although β,γ-methylene-ATP was inactive at P2Y receptors, β,γ-methylene-(N)-methanocarba-ATP was a potent hP2Y1 receptor agonist with an EC50 of 160 nM and was selective versus hP2Y2 and hP2Y4 receptors. The rates of hydrolysis of Northern (N) and Southern (S) methanocarba analogues of AMP by rat 5′-ectonucleotidase were negligible. The rates of hydrolysis of the corresponding triphosphates by recombinant rat NTPDase1 and 2 were studied. Both isomers were hydrolyzed by NTPDase 1 at about half the rate of ATP hydrolysis. The (N) isomer was hardly hydrolyzed by NTPDase 2, while the (S) isomer was hydrolyzed at one-third of the rate of ATP hydrolysis. This suggests that new, more stable and selective nucleotide agonists may be designed on the basis of

  16. The potency and specificity of the interaction between the IA3 inhibitor and its target aspartic proteinase from Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Phylip, L H; Lees, W E; Brownsey, B G

    2001-01-01

    The yeast IA3 polypeptide consists of only 68 residues, and the free inhibitor has little intrinsic secondary structure. IA3 showed subnanomolar potency toward its target, proteinase A from Saccharomyces cerevisiae, and did not inhibit any of a large number of aspartic proteinases with similar...... by the nontarget aspartic proteinases, it was not cleaved by proteinase A. The random coil IA3 polypeptide escapes cleavage by being stabilized in a helical conformation upon interaction with the active site of proteinase A. This results, paradoxically, in potent selective inhibition of the target enzyme....

  17. Globalisation and Higher Education

    NARCIS (Netherlands)

    Marginson, Simon; van der Wende, Marijk

    2007-01-01

    Economic and cultural globalisation has ushered in a new era in higher education. Higher education was always more internationally open than most sectors because of its immersion in knowledge, which never showed much respect for juridical boundaries. In global knowledge economies, higher education

  18. Sport jako perspektivní potenciál rozvoje zaměstnanosti v EU [Sport as a prospective potentional for employment in the EU states

    Directory of Open Access Journals (Sweden)

    Tomáš Dohnal

    2008-03-01

    Full Text Available Zaměstnanost a ekonomický růst jsou dvěma nejdůležitějšími cíli, sledovanými v rámci Lisabonské strategie, pomocí níž by se z Evropy v dalších letech měl stát celosvětově nejdynamičtější a nejkonkurenceschopnější ekonomický region. Vlády jednotlivých zemí doposud plně nerozpoznaly prorůstový a zaměstnanostní potenciál, který skrývají dopady sportu a průmyslu volného času. Jejich vyhodnocení je velmi složité a přesto, že byly mnohé analýzy ve vyspělých zemích světa publikovány, jejich praktické využití je teprve na počátku. Prostřednictvím vybraných oblastí jsou dokumentovány případové studie potenciálního rozvoje zaměstnanosti iniciované rozvojem sportu. Možný vliv na potenciál zaměstnanosti a uplatnění na trhu práce se také staly jedním z významných faktorů tvorby nových curricul oboru rekreologie, které jsou zpracovávány v souvislosti s projektem Evropských sociálních fondů. [Employment and economic growth are monitored as two of the most important goals within the Lisbon strategy, which should make Europe the world's most dynamic and competitive region in the coming years. Governments of member states have not yet fully recognized the growth and employment potential of sport and leisure time industry. The valuation is very complicated and even though some analyses were already published in developed countries, the practical use is at the beginning. Case studies prove potential growth of employment in selected fields initiated by development of sport and leisure time industry. These fields include tourism, production and selling of sport equipment, services (physical condition, sport events, professional sport, media etc. The Czech Republic has an employment in sport of 0,3% which is just and average within the EU. Europe will need around 800 000 to 1 million professional experts for sport and leisure time. Considering this, all related fields of

  19. Utilizing relative potency factors (RPF) and threshold of toxicological concern (TTC) concepts to assess hazard and human risk assessment profiles of environmental metabolites: a case study.

    Science.gov (United States)

    Terry, C; Rasoulpour, R J; Knowles, S; Billington, R

    2015-03-01

    , X11719474 found in soil, crops and, potentially, at low concentrations, in groundwater, was the most extensively studied, with genetic, acute, short-term rat and dog, rodent reproductive and developmental toxicity studies, and MoA studies conducted. These data supported that the toxicity profile for X11719474 was limited to liver effects via the same MoA as the parent and, overall, X11719474 was significantly less toxic than parent. Subsequently, the comparative toxicology programme was extended to cover all metabolites of sulfoxaflor. Based on structure (i.e., similarity of metabolite structures to one another), toxic effects in comparison with parent (i.e., consistency of the toxicity profiles and confidence in terms of ability to read across), residue compartment (e.g., crop, soil, water) and predicted level of exposure, fewer studies were required for establishing safety of these metabolites compared to X11719474. For example, for some metabolites with very low predicted environmental concentrations only genotoxicity testing was required. For some metabolites with low predicted concentrations, for example only present in liver, a TTC approach was utilized. This strategy of comparative assessment utilizing MoA data, relative potency, hazard characterization, read-across, predicted exposure and TTC provided a robust database, which minimized animal use, comprehensively assessed the hazard and human risk presented by these metabolites. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. POTENSI ANTI-HIPERKOLESTEROLEMIA EKASTRAK CASSIA VERA [Anti-hypercholesterolemic Potency of Cassia Vera (Cinnamomum burmanni Nees ex Blume Bark Extract

    Directory of Open Access Journals (Sweden)

    Fauzan Azima1

    2004-08-01

    Full Text Available There has been limited report on the phytochemical content of cassia vera bark extract, and its potency as anti-hypercholesterolemic in rabbit is not known yet. The objectives of this research was to determine the phytochemical content and potency of anti-hypercholesterolemic of cassia vera bark extract using rabbit as the animal model.The research was devided into three stages, namely: (1 preparing cassia vera extraction with ethanol 96%; (2 analyzing phytochemical contents of cassia vera bark extract; (3 in vivo experiment, where twenty New Zealand White rabbits aged 5 months were used. Experimental rabbits were divided into 5 groups. The rabbits were fed with atherogenic cholesterol (0.1% as positive control, RB11 standard feed as negative control, or cassia vera extracts (100 mg/kg/day or 200 mg/kg/day or fenofibrat (15 mg/day together with the atherogenic feed for 12 weeks. Levels of serum total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol were determined at 0, 4, 8, and 12 week. At the end of the experiment formation of fatty liver were observed. The results showed that the ethanol extract of cassia vera bark contains total phenol (62.25%, flavonoids, triterpenoid, saponin and alkaloid. On the other hand, cassia vera bark extract was able to decrease total serum cholesterol from 443.3 mg/dl to 139.1 mg/dl, LDL cholesterol from 286.5 mg/dl to 95.8 mg/dl and triglyceride from 122.2 mg/dl to 61.2 mg/dl. Meanwhile, it increased HDL serum cholesterol from 29.1 mg/dl to 50.0 mg/dl in rabbit. It was also shown that the extract was able to decrease the everage fat globule on liver significantly from 27.47 globule to 3.59 globule per field view. Cassia vera bark extract with phytochemical content was found to be potential as anti-hypercholesterolemic and also in preventing fatty liver formatonr in rabbit

  1. RELATIVE POTENCIES OF MOTOR BLOCKADE AFTER INTRATHECAL ROPIVACAINE, LEVOBUPIVACAINE AND BUPIVACAINE

    Directory of Open Access Journals (Sweden)

    Udayagiri Ravisankar

    2015-12-01

    Full Text Available AIM Ever since the times spinal anaesthesia has been introduced by August Bier, multiple drugs at different dosages, concentrations and differing baricities have been studied. This study was conducted to compare the anaesthetic efficacy of intrathecal isobaric 0.5% ropivacaine, isobaric 0.5% bupivacaine and isobaric levobupivacaine in lower abdominal and lower limb surgeries, in 150 ASA grade I and II patients of both sexes in the age group of 19-65 years undergoing elective surgery under spinal anaesthesia. MATERIALS & METHODS After getting ethical committee approval and informed written consent from the patients, 150 patients were allocated into three groups of 50 patients each. The baseline pulse rate and mean arterial pressure were recorded. The first group A received 3ml of isobaric 0.5% ropivacaine (5mg/ml, the second group received 3ml of isobaric 0.5% bupivacaine and the third group C received 3ml of isobaric levobupivacaine intrathecally. The onset of sensory and motor blocks, duration of sensory and motor blocks was recorded in three groups. RESULTS The results were analyzed statistically using epidemiologically information package. On comparison of data we have found that the intrathecal isobaric 0.5% ropivacaine produces delayed onset of both sensory and motor block but of shorter duration which is statistically significant when compared with that of isobaric 0.5% bupivacaine and levobupivacaine. There is no significant inter-group difference between bupivacaine and levobupivacaine except for the mean duration of sensory block, which is more in levobupivacaine group. The quality of motor block which was assessed by Bromage scale, shows relatively lesser degree of motor block for ropivacaine group, when compared with that of bupivacaine and levobupivacaine groups. The haemodynamics were also recorded. The incidence of hypotension and Bradycardia is more in bupivacaine group. The height of block (peak sensory level is higher for

  2. The stress response and anesthetic potency of unilateral spinal anesthesia for total Hip Replacement in geriatric patients.

    Science.gov (United States)

    Zhu, Li; Tian, Chun; Li, Min; Peng, Ming-Qing; Ma, Kun-Long; Wang, Zhong-Lin; Ding, Jia-Hui; Cai, Yi

    2014-11-01

    Recently, some scholars suggested that it is important to keep a stablehemodynamic state and prevent the stress responses in geriatric patients undergoing total hip replacement (THR). We conducted this randomized prospective study to observe anesthetic potency of unilateral spinal anesthesia and stress response to it in geriatric patients during THR. We compared the effect of unilateral spinal and bilateral spinal on inhibition of stress response through measuring Norepinephrine (NE), epinephrine (E) and cortisol (CORT). Plasma concentrations of NE, E and CORT were determined in blood samples using ELISA (enzyme-linked immunosorbent assays) at three time points: To (prior to anesthesia) T1 (at the time point of skin closure), T2 (twenty-four hours after the operation). Sixty patients were randomly divided into two groups: group A (unilateral spinal anesthesia) and group B (conventional bilateral spinal anesthesia). 7.5tymg of hypobaric bupivacaine were injected into subarachnoid cavity at group A and 12mg hypobaric bupivacaine were given at group B. The onset time of sensory and motor block, loss of pinprick sensation, degree of motor block, regression of sensory and motor blocks and hemodynamic changes were also recorded. These data were used to evaluate anesthetic potency of spinal anesthesia. The results of this experiment show that unilateral spinal anesthesia can provide restriction of sensory and motor block, minimize the incidence of hypotension and prevent the stress responses undergoing THR. It is optimal anesthesia procedure for geriatric patients by rapid subarachnoid injection of small doses of bupivacaine.

  3. Tuberculin purified protein derivative (PPD) immunoassay as an in vitro alternative assay for identity and confirmation of potency.

    Science.gov (United States)

    Ho, Mei M; Kairo, Satnam K; Corbel, Michael J

    2006-01-01

    Tuberculin purified protein derivative (PPD) currently can only be standardised by delayed hypersensitivity skin reactions in sensitised guinea pigs. An in vitro dot blot immunoassay was developed for both identity and confirmation of potency estimation of PPD. Polyclonal antibodies (mainly IgG) were generated and immunoreacted with human, bovine and, to lesser extent, avian PPD preparations. Combining size exclusion chromatography (FPLC-SEC) and dot blot immunoassay, the results showed that PPD preparations were mixtures of very heterogeneous tuberculoproteins ranging in size from very large aggregates to very small degraded molecules. All individual fractions of PPD separated by size were immunoreactive, although those of the largest molecular sizes appeared the most immunoreactive in this in vitro dot blot immunoassay. This method is very sensitive and specific to tuberculoproteins and can be an in vitro alternative for the in vivo intradermal skin assay which uses guinea pigs for identity of PPD preparations. Although the capacity of PPD to elicit cell-mediated immune responses on intradermal testing has to be confirmed by in vivo assay, the dot blot immunoassay offers a rapid, sensitive and animal-free alternative to in vivo testing for confirming the identity of PPD preparations with appropriate potencies. This alternative assay would be particularly useful for national regulatory laboratories for confirming the data of manufacturers and thus reducing the use of animals.

  4. Potency of Micro Hydro Power Plant Development Use of Kelampuak River Flow Located in Tamblang Village – Buleleng

    Directory of Open Access Journals (Sweden)

    Dewa Ngakan Ketut Putra Negara

    2012-11-01

    Full Text Available Need of electrical energy is increasing along with people population and economic growth. According to PLN data, Bali Province’s electrical consumption is predicted growth 5,6% in average every year. Until year 2007, electrical condition in Bali is categorized critical. If Power Plat in Bali, PLTG Gilimanuk that has power 130 MW is out of system, affecting Bali’s electrical back up is minus. Consecuenlly, it will be extinguishing if there is not adding power plan or new energy supply. This problem needs to be anticipated by use of thermal energy program such as coal, gas and geothermal and use of alternative energy such as solar, wind and ocean energies. Regency of Buleleng is one of Regency in Bali having potency of renewable energy development especially water resource. It has some rivers that have potency to be developed as a Micro Hydro Power Plant (PLTMH. One of them is Kelampuak River which is located in Tamblang Village. As a first step in developing of Micro Hydro Power Plant, it needs to be known water debit and head of the river. For that reason, it needs to be investigated debit and head of Kelampuak River so that it can be predicted the power can be generated.

  5. Reverse engineering truncations of an antimicrobial peptide dimer to identify the origins of potency and broad spectrum of action.

    Science.gov (United States)

    Anantharaman, Aparna; Sahal, Dinkar

    2010-08-26

    Antimicrobial peptides hold promise against antibiotic resistant pathogens. Here, to find the physicochemical origins of potency and broad spectrum antimicrobial action, we report the structure-activity relationships of synthetic intermediates (peptides A-D) of a potent lysine branched dimeric antibacterial peptide DeltaFd. Our studies show that a tetracationic character in a weak helical fold (peptide C) elicits potent but narrow spectrum antimicrobial activity [Minimum inhibitory concentrations (MICs) E. coli 10 microM, S. aureus>100 microM]. In contrast, a hexacationic character in a strong, amphipathic helix (DeltaFd) confers potent and broad spectrum action [MICs E. coli 2.5 microM, S. aureus 5 microM]. While DeltaFd caused rapid and potent permeabilization of the E. coli membranes, the less helical intermediates (peptides A-D) showed slow and weak to no responses. Two seminal findings that may aid future drug design are (a) at identical helicity, increasing charge enhanced outer membrane permeabilization, and (b) at identical charge, increasing helicity stimulated rate of outer membrane permeabilization and kill kinetics besides enhancing potency leading to broad spectrum action.

  6. Enhancement of human immunodeficiency virus type 1-DNA vaccine potency through incorporation of T-helper 1 molecular adjuvants.

    Science.gov (United States)

    Calarota, Sandra A; Weiner, David B

    2004-06-01

    It is clear that the development of a safe and effective vaccine for human immunodeficiency virus type 1 (HIV-1) remains a crucial goal for controlling the acquired immunodeficiency syndrome epidemic. At present, it is not clear what arm of the immune response correlates with protection from HIV-1 infection or disease. Therefore, a strong cellular and humoral immune response will likely be needed to control this infection. Among different vaccine alternatives, DNA vaccines appeared more than a decade ago, demonstrating important qualities of inducing both humoral and cellular immune responses in animal models. However, after several years and various clinical studies in humans, supporting the safety of the HIV-DNA vaccine strategies, it has become clear that their potency should be improved. One way to modulate and enhance the immune responses induced by a DNA vaccine is by including genetic adjuvants such as cytokines, chemokines, or T-cell costimulatory molecules as part of the vaccine itself. Particularly, vaccine immunogenicity can be modulated by factors that attract professional antigen-presenting cells, provide additional costimulation, or enhance the uptake of plasmid DNA. This review focuses on developments in the coadministration of molecular adjuvants for the enhancement of HIV-1 DNA-vaccine potency.

  7. An In Vitro Potency Assay for Monitoring the Immunomodulatory Potential of Stromal Cell-Derived Extracellular Vesicles

    Directory of Open Access Journals (Sweden)

    Karin Pachler

    2017-07-01

    Full Text Available The regenerative and immunomodulatory activity of mesenchymal stromal cells (MSCs is partially mediated by secreted vesicular factors. Extracellular vesicles (EVs exocytosed by MSCs are gaining increased attention as prospective non-cellular therapeutics for a variety of diseases. However, the lack of suitable in vitro assays to monitor the therapeutic potential of EVs currently restricts their application in clinical studies. We have evaluated a dual in vitro immunomodulation potency assay that reproducibly reports the inhibitory effect of MSCs on induced T-cell proliferation and the alloantigen-driven mixed leukocyte reaction of pooled peripheral blood mononuclear cells in a dose-dependent manner. Phytohemagglutinin-stimulated T-cell proliferation was inhibited by MSC-derived EVs in a dose-dependent manner comparable to MSCs. In contrast, inhibition of alloantigen-driven mixed leukocyte reaction was only observed for MSCs, but not for EVs. Our results support the application of a cell-based in vitro potency assay for reproducibly determining the immunomodulatory potential of EVs. Validation of this assay can help establish reliable release criteria for EVs for future clinical studies.

  8. Detection of estrogen receptor endocrine disruptor potency of commonly used organochlorine pesticides using the LUMI-CELL ER bioassay

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, J D; Chu, A C; Clark, G C [Xenobiotic Detection Systems, Inc., Durham, NC (United States); Chu, M D [Alta Analytical Perspectives, Wilmington, NC (United States); Denison, M S [Dept. of Environmental Toxicology, Univ. of California, Davis, CA (United States)

    2004-09-15

    In order to detect the endocrine disrupting potency of organochlorine pesticides and other compounds, BG-1 (human ovarian carcinoma) cells containing a stably transfected estrogenresponsive luciferase reporter gene plasmid (BG1Luc4E2), was used. This cell line, termed the LUMI-CELL trademark ER estrogenic cell bioassay system, responds in a time-, dose dependent- and chemical-specific manner with the induction of luciferase gene expression in response to exposure to estrogen (but not other steroid hormones) and estrogenic chemicals in a high-throughput screening (HTPS) format6. Here we describe studies in which the LUMI-CELL trademark ER estrogenic cell bioassay system was used for high throughput screening (HTPS) analysis of the estrogenic disrupting potency of several commonly used pesticides and organochlorines: p,p'DDT; p,p'-DDE; DDD; {alpha}a-chlordane; {psi}-chlordane; Kepone; Methoxychlor; Vinclozolin; Fenarimol; 2,4,5-Trichlorophenoxyacetic Acid; and Dieldrin. Our results demonstrate the utility of XDS's LUMI-CELL trademark ER bioassay HTPS system for screening chemicals for estrogenic activity.

  9. Detection of estrogen receptor endocrine disruptor potency of commonly used organochlorine pesticides using the LUMI-CELL ER bioassay

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, J.D.; Chu, A.C.; Clark, G.C. [Xenobiotic Detection Systems, Inc., Durham, NC (United States); Chu, M.D. [Alta Analytical Perspectives, Wilmington, NC (United States); Denison, M.S. [Dept. of Environmental Toxicology, Univ. of California, Davis, CA (United States)

    2004-09-15

    In order to detect the endocrine disrupting potency of organochlorine pesticides and other compounds, BG-1 (human ovarian carcinoma) cells containing a stably transfected estrogenresponsive luciferase reporter gene plasmid (BG1Luc4E2), was used. This cell line, termed the LUMI-CELL trademark ER estrogenic cell bioassay system, responds in a time-, dose dependent- and chemical-specific manner with the induction of luciferase gene expression in response to exposure to estrogen (but not other steroid hormones) and estrogenic chemicals in a high-throughput screening (HTPS) format6. Here we describe studies in which the LUMI-CELL trademark ER estrogenic cell bioassay system was used for high throughput screening (HTPS) analysis of the estrogenic disrupting potency of several commonly used pesticides and organochlorines: p,p'DDT; p,p'-DDE; DDD; {alpha}a-chlordane; {psi}-chlordane; Kepone; Methoxychlor; Vinclozolin; Fenarimol; 2,4,5-Trichlorophenoxyacetic Acid; and Dieldrin. Our results demonstrate the utility of XDS's LUMI-CELL trademark ER bioassay HTPS system for screening chemicals for estrogenic activity.

  10. Functional enhancement of AT1R potency in the presence of the TPαR is revealed by a comprehensive 7TM receptor co-expression screen.

    Directory of Open Access Journals (Sweden)

    Jonas Tind Hansen

    Full Text Available BACKGROUND: Functional cross-talk between seven transmembrane (7TM receptors can dramatically alter their pharmacological properties, both in vitro and in vivo. This represents an opportunity for the development of novel therapeutics that potentially target more specific biological effects while causing fewer adverse events. Although several studies convincingly have established the existence of 7TM receptor cross-talk, little is known about the frequencey and biological significance of this phenomenon. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the extent of synergism in 7TM receptor signaling, we took a comprehensive approach and co-expressed 123 different 7TM receptors together with the angiotensin II type 1 receptor (AT1R and analyzed how each receptor affected the angiotensin II (AngII response. To monitor the effect we used integrative receptor activation/signaling assay called Receptor Selection and Amplification Technology (R-SAT. In this screen the thromboxane A2α receptor (TPαR was the only receptor which significantly enhanced the AngII-mediated response. The TPαR-mediated enhancement of AngII signaling was significantly reduced when a signaling deficient receptor mutant (TPαR R130V was co-expressed instead of the wild-type TPαR, and was completely blocked both by TPαR antagonists and COX inhibitors inhibiting formation of thromboxane A2 (TXA2. CONCLUSIONS/SIGNIFICANCE: We found a functional enhancement of AT1R only when co-expressed with TPαR, but not with 122 other 7TM receptors. In addition, the TPαR must be functionally active, indicating the AT1R enhancement is mediated by a paracrine mechanism. Since we only found one receptor enhancing AT1R potency, our results suggest that functional augmentation through 7TM receptor cross-talk is a rare event that may require specific conditions to occur.

  11. Potency test of a rape accused in India – Rationale, problems and suggestions in light of the Criminal Law (Amendment Act, 2013

    Directory of Open Access Journals (Sweden)

    Md Shadab Raheel

    2016-12-01

    Full Text Available Indian legal system makes it mandatory to medically examine any accused of rape as well as other forms of sexual assault. Accused is brought in the police custody for conducting medical examination which includes general physical examination, potency test and evidence collection. The medical examination report of the accused is labeled as the “POTENCY TEST REPORT”. As per the changed definition of rape after Criminal Law (Amendment Act, 2013, potency test stands irrelevant in rape cases because the changed law does not require peno-vaginal intercourse to call it as rape. However, even after the change in definition of rape and laws related to it, potency test is still a mandatory part of medical examination of accused. Displeasure about the same has also been raised by a fast track court of Delhi. In this paper, we have discussed the rationale of potency test of sexual assault in light of Criminal Law Amendment Act (2013, court judgment and other available literature.

  12. Higher Education and Inequality

    Science.gov (United States)

    Brown, Roger

    2018-01-01

    After climate change, rising economic inequality is the greatest challenge facing the advanced Western societies. Higher education has traditionally been seen as a means to greater equality through its role in promoting social mobility. But with increased marketisation higher education now not only reflects the forces making for greater inequality…

  13. Higher Education in California

    Science.gov (United States)

    Public Policy Institute of California, 2016

    2016-01-01

    Higher education enhances Californians' lives and contributes to the state's economic growth. But population and education trends suggest that California is facing a large shortfall of college graduates. Addressing this short­fall will require strong gains for groups that have been historically under­represented in higher education. Substantial…

  14. Reimagining Christian Higher Education

    Science.gov (United States)

    Hulme, E. Eileen; Groom, David E., Jr.; Heltzel, Joseph M.

    2016-01-01

    The challenges facing higher education continue to mount. The shifting of the U.S. ethnic and racial demographics, the proliferation of advanced digital technologies and data, and the move from traditional degrees to continuous learning platforms have created an unstable environment to which Christian higher education must adapt in order to remain…

  15. Happiness in Higher Education

    Science.gov (United States)

    Elwick, Alex; Cannizzaro, Sara

    2017-01-01

    This paper investigates the higher education literature surrounding happiness and related notions: satisfaction, despair, flourishing and well-being. It finds that there is a real dearth of literature relating to profound happiness in higher education: much of the literature using the terms happiness and satisfaction interchangeably as if one were…

  16. Gender and Higher Education

    Science.gov (United States)

    Bank, Barbara J., Ed.

    2011-01-01

    This comprehensive, encyclopedic review explores gender and its impact on American higher education across historical and cultural contexts. Challenging recent claims that gender inequities in U.S. higher education no longer exist, the contributors--leading experts in the field--reveal the many ways in which gender is embedded in the educational…

  17. Quality of Higher Education

    DEFF Research Database (Denmark)

    Zou, Yihuan

    is about constructing a more inclusive understanding of quality in higher education through combining the macro, meso and micro levels, i.e. from the perspectives of national policy, higher education institutions as organizations in society, individual teaching staff and students. It covers both......Quality in higher education was not invented in recent decades – universities have always possessed mechanisms for assuring the quality of their work. The rising concern over quality is closely related to the changes in higher education and its social context. Among others, the most conspicuous...... changes are the massive expansion, diversification and increased cost in higher education, and new mechanisms of accountability initiated by the state. With these changes the traditional internally enacted academic quality-keeping has been given an important external dimension – quality assurance, which...

  18. Two acidic, anticoagulant PLA2 isoenzymes purified from the venom of monocled cobra Naja kaouthia exhibit different potency to inhibit thrombin and factor Xa via phospholipids independent, non-enzymatic mechanism.

    Directory of Open Access Journals (Sweden)

    Ashis K Mukherjee

    Full Text Available The monocled cobra (Naja kaouthia is responsible for snakebite fatality in Indian subcontinent and in south-western China. Phospholipase A2 (PLA2; EC 3.1.1.4 is one of the toxic components of snake venom. The present study explores the mechanism and rationale(s for the differences in anticoagulant potency of two acidic PLA2 isoenzymes, Nk-PLA2α (13463.91 Da and Nk-PLA2β (13282.38 Da purified from the venom of N. kaouthia.By LC-MS/MS analysis, these PLA2s showed highest similarity (23.5% sequence coverage with PLA2 III isolated from monocled cobra venom. The catalytic activity of Nk-PLA2β exceeds that of Nk-PLA2α. Heparin differentially regulated the catalytic and anticoagulant activities of these Nk-PLA2 isoenzymes. The anticoagulant potency of Nk-PLA2α was comparable to commercial anticoagulants warfarin, and heparin/antithrombin-III albeit Nk-PLA2β demonstrated highest anticoagulant activity. The anticoagulant action of these PLA2s was partially contributed by a small but specific hydrolysis of plasma phospholipids. The strong anticoagulant effect of Nk-PLA2α and Nk-PLA2β was achieved via preferential, non-enzymatic inhibition of FXa (Ki = 43 nM and thrombin (Ki = 8.3 nM, respectively. Kinetics study suggests that the Nk-PLA2 isoenzymes inhibit their "pharmacological target(s" by uncompetitive mechanism without the requirement of phospholipids/Ca(2+. The anticoagulant potency of Nk-PLA2β which is higher than that of Nk-PLA2α is corroborated by its superior catalytic activity, its higher capacity for binding to phosphatidylcholine, and its greater strength of thrombin inhibition. These PLA2 isoenzymes thus have evolved to affect haemostasis by different mechanisms. The Nk-PLA2β partially inhibited the thrombin-induced aggregation of mammalian platelets suggesting its therapeutic application in the prevention of unwanted clot formation.In order to develop peptide-based superior anticoagulant therapeutics, future application of Nk-PLA2

  19. Higher English for CFE

    CERN Document Server

    Bridges, Ann; Mitchell, John

    2015-01-01

    A brand new edition of the former Higher English: Close Reading , completely revised and updated for the new Higher element (Reading for Understanding, Analysis and Evaluation) - worth 30% of marks in the final exam!. We are working with SQA to secure endorsement for this title. Written by two highly experienced authors this book shows you how to practice for the Reading for Understanding, Analysis and Evaluation section of the new Higher English exam. This book introduces the terms and concepts that lie behind success and offers guidance on the interpretation of questions and targeting answer

  20. POTENSI NETRALISASI IMUNOGLOBULIN Y ANTITETANUS YANG DIISOLASI DARI TELUR AYAM (THE POTENCY NETRALIZATION OF ANTI TETANUS IMMUNOGLOBULIN Y THAT WERE ISOLATED FROM CHICKEN EGGS

    Directory of Open Access Journals (Sweden)

    I Nyoman Suartha

    2007-06-01

    Full Text Available The porpuse of study was to explore the potential use of? anti tetanus IgY from eggs yolk as a substitute for anti tetanus serum raised in ?horses. The eggs were collected from chickens which have previously been immunized with tetanus toxoid. Neutralization potency test of anti tetanus IgY determined by ?Spearman-Karber method.? The highest mean titer of anti tetanus of egg yolk was 80.16 ? 33.55 IU/ml and the lowest was 1.69 ? 0.63 IU/ml. The concentration? of purified IgY was 1.644 ? 0.424 mg/ml. Spearman-Karber value of potency of anti tetanus IgY are 35 IU/ml. ?This research concluded that Chickens was capable of produced of anti tetanus in eggs yolk with value of potency are 35 IU/ml.

  1. Study on potency of municipal solid waste conversion into renewable energy by thermal incineration and bioconversion: case study of Medan city

    Science.gov (United States)

    Sarah, Maya; Misran, Erni

    2018-03-01

    Municipal solid waste (MSW) in Medan City is facing problems either with the quantity and management of MSW. Local authority only dumped approximately 73.9% MSW in the landfill over the years. Spontaneous phenomena of methane formation in dumping site indicates the potency of MSW conversion into energy by biochemical conversion. On the contrary, the presence of plastics, woods, papers, etc. in the MSW show the potency of MSW to be treated by thermal conversion. Both thermal incineration and anaerobic digestion may convert MSW Medan City into energy. This study evaluates potency of MSW conversion into renewable energy using proximate and ultimate analysis. Overall, MSW of Medan City has the opportunities to be converted into energy by both thermal and biochemical conversion with a special requirement such as pre-dry the MSW prior incineration process and degrade organic MSW in a bioreactor.

  2. Integrated chemical and biological analysis to explain estrogenic potency in bile extracts of red mullet (Mullus barbatus)

    Energy Technology Data Exchange (ETDEWEB)

    Martínez-Gómez, Concepción, E-mail: concepcion.martinez@mu.ieo.es [Instituto Español de Oceanografía, Oceanografic Centre of Murcia, Varadero 1, San Pedro del Pinatar, 30740 Murcia (Spain); Lamoree, M.; Hamers, T.; Velzen, M. van; Kamstra, J.H. [VU University Amsterdam, Amsterdam Global Change Institute, Institute for Environmental Studies, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Fernández, B.; Benedicto, J.; León, V.M. [Instituto Español de Oceanografía, Oceanografic Centre of Murcia, Varadero 1, San Pedro del Pinatar, 30740 Murcia (Spain); Vethaak, A.D. [VU University Amsterdam, Amsterdam Global Change Institute, Institute for Environmental Studies, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Deltares, Marine and Coastal Systems, P.O. Box 177, 2600 MH Delft (Netherlands)

    2013-06-15

    Highlights: •In vitro estrogenic activity was quantified in male bile extracts of feral red mullet. •Major PAH metabolites and alkylphenols were quantified in the same fish bile extracts. •Contribution of these compounds to the estrogenicity measured was found negligible. •PAH and alkylphenol fish exposure was low in most of the studied Mediterranean sites. •High estrogenicity in male fish from Mar Menor lagoon warrants further studies. -- Abstract: A biological screening was performed to establish the total exposure to estrogenic compounds of red mullet (Mullus barbatus) collected at several sites along the Spanish Mediterranean coast by testing male fish bile extracts using the in vitro ER-LUC reporter gene assay. In addition, major metabolites were identified and measurements of OH-PAHs (1-naphthol, 9-phenantrol, 9-fluorenol, 1-pyrenol, 1OH-BaP and 3OH-BaP) and alkylphenols (4-n-nonylphenol (4-n-NP) and 4-tertoctylphenol (4-tert-OP)) in the same fish bile extracts were taken by gas chromatography–mass spectrometry in electron ionization mode (GC–EI-MS). Relative in vitro estrogenic potencies of the chemically quantified compounds were also tested. The highest biliary concentrations of 1-pyrenol, 9-fluorenol and 4-n-NP were found in fish from Barcelona and from the Mar Menor coastal lagoon. However, these concentrations can be considered relatively low compared to values reported in red mullet from other polluted waters in the Mediterranean Sea. The contribution of 1-pyrenol, 4-n-NP and 4-tert-OP to the total estrogenic potency measured in male fish bile was found to be negligible, indicating the presence of other estrogenic compounds in red mullet bile. Estrogenic potency in bile from male fish was markedly elevated in Mar Menor lagoon (234.8 ± 5.7 pg E2EQ/μl), and further research will be necessary to explain whether the presence of natural and synthetic-hormones in the lagoon contributed to this finding. Values of approximately 15–16 E2EQ pg

  3. Integrated chemical and biological analysis to explain estrogenic potency in bile extracts of red mullet (Mullus barbatus)

    International Nuclear Information System (INIS)

    Martínez-Gómez, Concepción; Lamoree, M.; Hamers, T.; Velzen, M. van; Kamstra, J.H.; Fernández, B.; Benedicto, J.; León, V.M.; Vethaak, A.D.

    2013-01-01

    Highlights: •In vitro estrogenic activity was quantified in male bile extracts of feral red mullet. •Major PAH metabolites and alkylphenols were quantified in the same fish bile extracts. •Contribution of these compounds to the estrogenicity measured was found negligible. •PAH and alkylphenol fish exposure was low in most of the studied Mediterranean sites. •High estrogenicity in male fish from Mar Menor lagoon warrants further studies. -- Abstract: A biological screening was performed to establish the total exposure to estrogenic compounds of red mullet (Mullus barbatus) collected at several sites along the Spanish Mediterranean coast by testing male fish bile extracts using the in vitro ER-LUC reporter gene assay. In addition, major metabolites were identified and measurements of OH-PAHs (1-naphthol, 9-phenantrol, 9-fluorenol, 1-pyrenol, 1OH-BaP and 3OH-BaP) and alkylphenols (4-n-nonylphenol (4-n-NP) and 4-tertoctylphenol (4-tert-OP)) in the same fish bile extracts were taken by gas chromatography–mass spectrometry in electron ionization mode (GC–EI-MS). Relative in vitro estrogenic potencies of the chemically quantified compounds were also tested. The highest biliary concentrations of 1-pyrenol, 9-fluorenol and 4-n-NP were found in fish from Barcelona and from the Mar Menor coastal lagoon. However, these concentrations can be considered relatively low compared to values reported in red mullet from other polluted waters in the Mediterranean Sea. The contribution of 1-pyrenol, 4-n-NP and 4-tert-OP to the total estrogenic potency measured in male fish bile was found to be negligible, indicating the presence of other estrogenic compounds in red mullet bile. Estrogenic potency in bile from male fish was markedly elevated in Mar Menor lagoon (234.8 ± 5.7 pg E2EQ/μl), and further research will be necessary to explain whether the presence of natural and synthetic-hormones in the lagoon contributed to this finding. Values of approximately 15–16 E2EQ pg

  4. Planning for Higher Education.

    Science.gov (United States)

    Lindstrom, Caj-Gunnar

    1984-01-01

    Decision processes for strategic planning for higher education institutions are outlined using these parameters: institutional goals and power structure, organizational climate, leadership attitudes, specific problem type, and problem-solving conditions and alternatives. (MSE)

  5. Advert for higher education

    OpenAIRE

    N.V. Provozin; А.S. Teletov

    2011-01-01

    The article discusses the features advertising higher education institution. The analysis results of marketing research students for their choice of institutions and further study. Principles of the advertising campaign on three levels: the university, the faculty, the separate department.

  6. On higher derivative gravity

    International Nuclear Information System (INIS)

    Accioly, A.J.

    1987-01-01

    A possible classical route conducting towards a general relativity theory with higher-derivatives starting, in a sense, from first principles, is analysed. A completely causal vacuum solution with the symmetries of the Goedel universe is obtained in the framework of this higher-derivative gravity. This very peculiar and rare result is the first known vcuum solution of the fourth-order gravity theory that is not a solution of the corresponding Einstein's equations.(Author) [pt

  7. Higher Spins & Strings

    CERN Multimedia

    CERN. Geneva

    2014-01-01

    The conjectured relation between higher spin theories on anti de-Sitter (AdS) spaces and weakly coupled conformal field theories is reviewed. I shall then outline the evidence in favour of a concrete duality of this kind, relating a specific higher spin theory on AdS3 to a family of 2d minimal model CFTs. Finally, I shall explain how this relation fits into the framework of the familiar stringy AdS/CFT correspondence.

  8. Relative effect potency estimates of dioxin-like activity for dioxins, furans, and dioxin-like PCBs in adults based on two thyroid outcomes.

    Science.gov (United States)

    Trnovec, Tomáš; Jusko, Todd A; Šovčíková, Eva; Lancz, Kinga; Chovancová, Jana; Patayová, Henrieta; Palkovičová, L'ubica; Drobná, Beata; Langer, Pavel; Van den Berg, Martin; Dedik, Ladislav; Wimmerová, Soňa

    2013-08-01

    Toxic equivalency factors (TEFs) are an important component in the risk assessment of dioxin-like human exposures. At present, this concept is based mainly on in vivo animal experiments using oral dosage. Consequently, the current human TEFs derived from mammalian experiments are applicable only for exposure situations in which oral ingestion occurs. Nevertheless, these "intake" TEFs are commonly-but incorrectly-used by regulatory authorities to calculate "systemic" toxic equivalents (TEQs) based on human blood and tissue concentrations, which are used as biomarkers for either exposure or effect. We sought to determine relative effect potencies (REPs) for systemic human concentrations of dioxin-like mixture components using thyroid volume or serum free thyroxine (FT4) concentration as the outcomes of interest. We used a benchmark concentration and a regression-based approach to compare the strength of association between each dioxin-like compound and the thyroid end points in 320 adults residing in an organochlorine-polluted area of eastern Slovakia. REPs calculated from thyroid volume and FT4 were similar. The regression coefficient (β)-derived REP data from thyroid volume and FT4 level were correlated with the World Health Organization (WHO) TEF values (Spearman r = 0.69, p = 0.01 and r = 0.62, p = 0.03, respectively). The calculated REPs were mostly within the minimum and maximum values for in vivo REPs derived by other investigators. Our REPs calculated from thyroid end points realistically reflect human exposure scenarios because they are based on chronic, low-dose human exposures and on biomarkers reflecting body burden. Compared with previous results, our REPs suggest higher sensitivity to the effects of dioxin-like compounds.

  9. [Experimental-morphological study of morphogenetic potencies of homogeneous aggregates of different types of cells from the freshwater sponge Ephydatia fluviatilis (L.)].

    Science.gov (United States)

    Nikitin, N S

    1977-01-01

    The morphogenetic potencies of somatic cells of the fresh-water sponge Ephydatia fluviatilis in the developing aggregates depend on their initial specialization and the number of cells in the aggregate. The aggregates of nucleolar amoebocytes consisting of 500 or more cells have the highest morphogenetic potencies. All main cell types can arise in the developing homogeneous aggregates of nucleolar amoebocytes. The fine structure of nucleolar amoebocytes at different stages of development of the homogeneous aggregates was studied by means of electron microscopy. The structural rearrangements are described which accompany the process of redifferentiation of the nucleolar amoebocytes in other cell types.

  10. Single prostacyclin receptor of gel-filtered platelets provides a correlation with antiaggregatory potency of PGI2 mimics

    International Nuclear Information System (INIS)

    Eggerman, T.L.; Hartzell, C.J.; Selfe, S.; Andersen, N.H.

    1987-01-01

    Gel-filtered human platelets (GFP) display only a single binding site for [ 3 H]-PGI2: KD = 61nM, 234 fmol/10(8) platelets (1410 sites/platelet). Platelet-rich plasma (PRP) displays the same receptor density but the KD value increases to 123 nM due to protein binding of PGI2 which lowers its effective concentration. The [ 3 H]-PGI2/GFP binding assay has been used to evaluate the molecular basis of aggregation inhibition for prostacyclin analogs and mimics, three PGE type structures, and PGD2. Antiaggregatory IC50s and radioligand binding IC50s correlate for PGE2, E1, and six PGI2 analogs. PGD2, and to a lesser extent 6-oxo-PGE1, display greater antiaggregatory potency than expected based on PGI2-binding site affinity data

  11. Anticonvulsant Potencies of the Enantiomers of the Neurosteroids Androsterone and Etiocholanolone Exceed those of the Natural Forms

    Science.gov (United States)

    Zolkowska, Dorota; Dhir, Ashish; Krishnan, Kathiresan; Covey, Douglas F.; Rogawski, Michael A.

    2014-01-01

    Rationale Androsterone [(3α,5α)-3-hydroxyandrostan-17-one; 5α,3α-A] and its 5β-epimer etiocholanolone [(3α,5β)-3-hydroxyandrostan-17-one; 5β,3α-A)], the major excreted metabolites of testosterone, are neurosteroid positive modulators of GABAA receptors. Such neurosteroids typically show enantioselectivity in which the natural form is more potent than the corresponding unnatural enantiomer. For 5α,3α-A and 5β,3α-A, the unnatural enantiomers are more potent at GABAA receptors than the natural forms. Objectives The aim of this study was to compare the anticonvulsant potencies and time courses of 5α,3α-A and 5β,3α-A with their enantiomers in mouse seizure models. Methods Steroids were administered intraperitoneally to male NIH Swiss mice 15 min (or up to 6 h in time course experiments) prior to administration of an electrical stimulus in the 6-Hz or maximal electroshock (MES) seizure tests or the convulsant pentylenetetrazol (PTZ). Results In the 6-Hz test, the ED50 values of ent-5α,3α-A was 5.0 mg/kg whereas the value for 5α,3α-A was 12.1 mg/kg; the corresponding values in the PTZ seizure test were 22.8 and 51.8 mg/kg. Neurosteroid GABAA receptor positive allosteric modulators are generally weak in the MES test and this was confirmed in the present study. However, the atypical relative potency relationship was maintained with ED50 values of 140 and 223 mg/kg for ent-5α,3α- A and 5α,3α-A, respectively. Similar relationships were obtained for the 5β-isomers, except that the enantioselectivity was accentuated. In the 6-Hz and PTZ tests, the ED50 values of ent-5β,3α-A were 11.8 and 20.4 mg/kg whereas the values for 5β,3α-A were 57.6 and 109.1 mg/kg. Protective activity in the 6-Hz test of ent-5α,3α-A persisted for somewhat longer (~5 h) than for 5α,3α-A (~4 h); protection by ent-5β,3α-A also persisted longer (~3 h) than for 5β,3α-A (~2 h). Conclusions The unnatural enantiomers of 17-keto androgen class neurosteroids have greater in

  12. Probing the inhibitory potency of epigallocatechin gallate against human γB-crystallin aggregation: Spectroscopic, microscopic and simulation studies

    Science.gov (United States)

    Chaudhury, Susmitnarayan; Dutta, Anirudha; Bag, Sudipta; Biswas, Pranandita; Das, Amit Kumar; Dasgupta, Swagata

    2018-03-01

    Aggregation of human ocular lens proteins, the crystallins is believed to be one of the key reasons for age-onset cataract. Previous studies have shown that human γD-crystallin forms amyloid like fibres under conditions of low pH and elevated temperature. In this article, we have investigated the aggregation propensity of human γB-crystallin in absence and presence of epigallocatechin gallate (EGCG), in vitro, when exposed to stressful conditions. We have used different spectroscopic and microscopic techniques to elucidate the inhibitory effect of EGCG towards aggregation. The experimental results have been substantiated by molecular dynamics simulation studies. We have shown that EGCG possesses inhibitory potency against the aggregation of human γB-crystallin at low pH and elevated temperature.

  13. Daily Use, Especially of High-Potency Cannabis, Drives the Earlier Onset of Psychosis in Cannabis Users

    Science.gov (United States)

    Di Forti, Marta; Sallis, Hannah; Allegri, Fabio; Trotta, Antonella; Ferraro, Laura; Stilo, Simona A.; Marconi, Arianna; La Cascia, Caterina; Reis Marques, Tiago; Pariante, Carmine; Dazzan, Paola; Mondelli, Valeria; Paparelli, Alessandra; Kolliakou, Anna; Prata, Diana; Gaughran, Fiona; David, Anthony S.; Morgan, Craig; Stahl, Daniel; Khondoker, Mizanur; MacCabe, James H.; Murray, Robin M.

    2014-01-01

    Cannabis use is associated with an earlier age of onset of psychosis (AOP). However, the reasons for this remain debated. Methods: We applied a Cox proportional hazards model to 410 first-episode psychosis patients to investigate the association between gender, patterns of cannabis use, and AOP. Results: Patients with a history of cannabis use presented with their first episode of psychosis at a younger age (mean years = 28.2, SD = 8.0; median years = 27.1) than those who never used cannabis (mean years = 31.4, SD = 9.9; median years = 30.0; hazard ratio [HR] = 1.42; 95% CI: 1.16–1.74; P cannabis at age 15 or younger had an earlier onset of psychosis (mean years = 27.0, SD = 6.2; median years = 26.9) than those who had started after 15 years (mean years = 29.1, SD = 8.5; median years = 27.8; HR = 1.40; 95% CI: 1.06–1.84; P = .050). Importantly, subjects who had been using high-potency cannabis (skunk-type) every day had the earliest onset (mean years = 25.2, SD = 6.3; median years = 24.6) compared to never users among all the groups tested (HR = 1.99; 95% CI: 1.50- 2.65; P cannabis had an onset an average of 6 years earlier than that of non-cannabis users. Conclusions: Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users. PMID:24345517

  14. Variability of cannabis potency in the Venice area (Italy): a survey over the period 2010-2012.

    Science.gov (United States)

    Zamengo, Luca; Frison, Giampietro; Bettin, Chiara; Sciarrone, Rocco

    2014-01-01

    Cannabis is the most widely used illicit substance globally, with an estimated annual prevalence in 2010 of 2.6-5.0% of the adult population. Concerns have been expressed about increases in the potency of cannabis products. A high tetrahydrocannabinol (THC) content can increase anxiety, depression, and psychotic symptoms, and can increase the risk of dependence and adverse effects on the respiratory and cardiovascular systems in regular users. The aim of this study was to report statistical data about the potency of cannabis products seized in the north-east of Italy, in a geographical area centred in Venice and extending for more than 10,000  km(2) with a population of more than two million, by investigating the variability observed in THC levels of about 4000 samples of cannabis products analyzed over the period 2010-2012. Overall median THC content showed an increasing trend over the study period from about 6.0% to 8.1% (6.2-8.9% for cannabis resin, 5.1-7.6% for herbal cannabis). The variation in the THC content of individual samples was very large, ranging from 0.3% to 31% for cannabis resin and from 0.1 to 19% for herbal cannabis. Median CBN:THC ratios showed a slightly decreasing trend over the study period, from 0.09 (2010) to 0.03 (2012), suggesting an increasing freshness of submitted materials. Median CBD:THC ratios also showed a decreasing trend over the study from about 0.52 (2010) to 0.18 (2012), likely due to the increase in submissions of materials from indoor and domestic cultivation with improved breeding methods. Copyright © 2013 John Wiley & Sons, Ltd.

  15. Adaptability to pain is associated with potency of local pain inhibition, but not conditioned pain modulation: a healthy human study.

    Science.gov (United States)

    Zheng, Zhen; Wang, Kelun; Yao, Dongyuan; Xue, Charlie C L; Arendt-Nielsen, Lars

    2014-05-01

    This study investigated the relationship between pain sensitivity, adaptability, and potency of endogenous pain inhibition, including conditioned pain modulation (CPM) and local pain inhibition. Forty-one healthy volunteers (20 male, 21 female) received conditioning stimulation (CS) over 2 sessions in a random order: tonic heat pain (46 °C) on the right leg for 7 minutes and cold pressor pain (1 °C to 4 °C) on the left hand for 5 minutes. Participants rated the intensity of pain continuously using a 0 to 10 electronic visual analogue scale. The primary outcome measures were pressure pain thresholds (PPT) measured at the heterotopic and homotopic location to the CS sites before, during, and 20 minutes after CS. Two groups of participants, pain adaptive and pain nonadaptive, were identified based on their response to pain in the cold pressor test. Pain-adaptive participants showed a pain reduction between peak pain and pain at end of the test by at least 2 of 10 (n=16); whereas the pain-nonadaptive participants reported unchanged peak pain during 5-minute CS (n=25). Heterotopic PPTs during the CS did not differ between the 2 groups. However, increased homotopic PPTs measured 20 minutes after CS correlated with the amount of pain reduction during CS. These results suggest that individual sensitivity and adaptability to pain does not correlate with the potency of CPM. Adaptability to pain is associated with longer-lasting local pain inhibition. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  16. High potency inhibition of hERG potassium channels by the sodium–calcium exchange inhibitor KB-R7943

    Science.gov (United States)

    Cheng, Hongwei; Zhang, Yihong; Du, Chunyun; Dempsey, Christopher E; Hancox, Jules C

    2012-01-01

    BACKGROUND AND PURPOSE KB-R7943 is an isothiourea derivative that is used widely as a pharmacological inhibitor of sodium–calcium exchange (NCX) in experiments on cardiac and other tissue types. This study investigated KB-R7943 inhibition of hERG (human ether-à-go-go-related gene) K+ channels that underpin the cardiac rapid delayed rectifier potassium current, IKr. EXPERIMENTAL APPROACH Whole-cell patch-clamp measurements were made of hERG current (IhERG) carried by wild-type or mutant hERG channels and of native rabbit ventricular IKr. Docking simulations utilized a hERG homology model built on a MthK-based template. KEY RESULTS KB-R7943 inhibited both IhERG and native IKr rapidly on membrane depolarization with IC50 values of ∼89 and ∼120 nM, respectively, for current tails at −40 mV following depolarizing voltage commands to +20 mV. Marked IhERG inhibition also occurred under ventricular action potential voltage clamp. IhERG inhibition by KB-R7943 exhibited both time- and voltage-dependence but showed no preference for inactivated over activated channels. Results of alanine mutagenesis and docking simulations indicate that KB-R7943 can bind to a pocket formed of the side chains of aromatic residues Y652 and F656, with the compound's nitrobenzyl group orientated towards the cytoplasmic side of the channel pore. The structurally related NCX inhibitor SN-6 also inhibited IhERG, but with a markedly reduced potency. CONCLUSIONS AND IMPLICATIONS KB-R7943 inhibits IhERG/IKr with a potency that exceeds that reported previously for acute cardiac NCX inhibition. Our results also support the feasibility of benzyloxyphenyl-containing NCX inhibitors with reduced potential, in comparison with KB-R7943, to inhibit hERG. PMID:21950687

  17. Fuel Class Higher Alcohols

    KAUST Repository

    Sarathy, Mani

    2016-08-17

    This chapter focuses on the production and combustion of alcohol fuels with four or more carbon atoms, which we classify as higher alcohols. It assesses the feasibility of utilizing various C4-C8 alcohols as fuels for internal combustion engines. Utilizing higher-molecular-weight alcohols as fuels requires careful analysis of their fuel properties. ASTM standards provide fuel property requirements for spark-ignition (SI) and compression-ignition (CI) engines such as the stability, lubricity, viscosity, and cold filter plugging point (CFPP) properties of blends of higher alcohols. Important combustion properties that are studied include laminar and turbulent flame speeds, flame blowout/extinction limits, ignition delay under various mixing conditions, and gas-phase and particulate emissions. The chapter focuses on the combustion of higher alcohols in reciprocating SI and CI engines and discusses higher alcohol performance in SI and CI engines. Finally, the chapter identifies the sources, production pathways, and technologies currently being pursued for production of some fuels, including n-butanol, iso-butanol, and n-octanol.

  18. Higher spin gauge theories

    CERN Document Server

    Henneaux, Marc; Vasiliev, Mikhail A

    2017-01-01

    Symmetries play a fundamental role in physics. Non-Abelian gauge symmetries are the symmetries behind theories for massless spin-1 particles, while the reparametrization symmetry is behind Einstein's gravity theory for massless spin-2 particles. In supersymmetric theories these particles can be connected also to massless fermionic particles. Does Nature stop at spin-2 or can there also be massless higher spin theories. In the past strong indications have been given that such theories do not exist. However, in recent times ways to evade those constraints have been found and higher spin gauge theories have been constructed. With the advent of the AdS/CFT duality correspondence even stronger indications have been given that higher spin gauge theories play an important role in fundamental physics. All these issues were discussed at an international workshop in Singapore in November 2015 where the leading scientists in the field participated. This volume presents an up-to-date, detailed overview of the theories i...

  19. Quality of Higher Education

    DEFF Research Database (Denmark)

    Zou, Yihuan; Zhao, Yingsheng; Du, Xiangyun

    . This transformation involves a broad scale of change at individual level, organizational level, and societal level. In this change process in higher education, staff development remains one of the key elements for university innovation and at the same time demands a systematic and holistic approach.......This paper starts with a critical approach to reflect on the current practice of quality assessment and assurance in higher education. This is followed by a proposal that in response to the global challenges for improving the quality of higher education, universities should take active actions...... of change by improving the quality of teaching and learning. From a constructivist perspective of understanding education and learning, this paper also discusses why and how universities should give more weight to learning and change the traditional role of teaching to an innovative approach of facilitation...

  20. Reputation in Higher Education

    DEFF Research Database (Denmark)

    Martensen, Anne; Grønholdt, Lars

    2005-01-01

    leaders of higher education institutions to set strategic directions and support their decisions in an effort to create even better study programmes with a better reputation. Finally, managerial implications and directions for future research are discussed.Keywords: Reputation, image, corporate identity......The purpose of this paper is to develop a reputation model for higher education programmes, provide empirical evidence for the model and illustrate its application by using Copenhagen Business School (CBS) as the recurrent case. The developed model is a cause-and-effect model linking image...

  1. Reputation in Higher Education

    DEFF Research Database (Denmark)

    Plewa, Carolin; Ho, Joanne; Conduit, Jodie

    2016-01-01

    Reputation is critical for institutions wishing to attract and retain students in today's competitive higher education setting. Drawing on the resource based view and configuration theory, this research proposes that Higher Education Institutions (HEIs) need to understand not only the impact...... of independent resources but of resource configurations when seeking to achieve a strong, positive reputation. Utilizing fuzzy set qualitative comparative analysis (fsQCA), the paper provides insight into different configurations of resources that HEIs can utilize to build their reputation within their domestic...

  2. Navigating in higher education

    DEFF Research Database (Denmark)

    Thingholm, Hanne Balsby; Reimer, David; Keiding, Tina Bering

    Denne rapport er skrevet på baggrund af spørgeskemaundersøgelsen – Navigating in Higher Education (NiHE) – der rummer besvarelser fra 1410 bachelorstuderende og 283 undervisere fordelt på ni uddannelser fra Aarhus Universitet: Uddannelsesvidenskab, Historie, Nordisk sprog og litteratur, Informati......Denne rapport er skrevet på baggrund af spørgeskemaundersøgelsen – Navigating in Higher Education (NiHE) – der rummer besvarelser fra 1410 bachelorstuderende og 283 undervisere fordelt på ni uddannelser fra Aarhus Universitet: Uddannelsesvidenskab, Historie, Nordisk sprog og litteratur...

  3. Exploring Higher Thinking.

    Science.gov (United States)

    Conover, Willis M.

    1992-01-01

    Maintains that the social studies reform movement includes a call for the de-emphasis of rote memory and more attention to the development of higher-order thinking skills. Discusses the "thinking tasks" concept derived from the work of Hilda Taba and asserts that the tasks can be used with almost any social studies topic. (CFR)

  4. Higher-Order Hierarchies

    DEFF Research Database (Denmark)

    Ernst, Erik

    2003-01-01

    This paper introduces the notion of higher-order inheritance hierarchies. They are useful because they provide well-known benefits of object-orientation at the level of entire hierarchies-benefits which are not available with current approaches. Three facets must be adressed: First, it must be po...

  5. Inflation from higher dimensions

    International Nuclear Information System (INIS)

    Shafi, Q.

    1987-01-01

    We argue that an inflationary phase in the very early universe is related to the transition from a higher dimensional to a four-dimensional universe. We present details of a previously considered model which gives sufficient inflation without fine tuning of parameters. (orig.)

  6. Higher Education Funding Formulas.

    Science.gov (United States)

    McKeown-Moak, Mary P.

    1999-01-01

    One of the most critical components of the college or university chief financial officer's job is budget planning, especially using formulas. A discussion of funding formulas looks at advantages, disadvantages, and types of formulas used by states in budgeting for higher education, and examines how chief financial officers can position the campus…

  7. Liberty and Higher Education.

    Science.gov (United States)

    Thompson, Dennis F.

    1989-01-01

    John Stuart Mill's principle of liberty is discussed with the view that it needs to be revised to guide moral judgments in higher education. Three key elements need to be modified: the action that is constrained; the constraint on the action; and the agent whose action is constrained. (MLW)

  8. Fuel Class Higher Alcohols

    KAUST Repository

    Sarathy, Mani

    2016-01-01

    This chapter focuses on the production and combustion of alcohol fuels with four or more carbon atoms, which we classify as higher alcohols. It assesses the feasibility of utilizing various C4-C8 alcohols as fuels for internal combustion engines

  9. Evaluation in Higher Education

    Science.gov (United States)

    Bognar, Branko; Bungic, Maja

    2014-01-01

    One of the means of transforming classroom experience is by conducting action research with students. This paper reports about the action research with university students. It has been carried out within a semester of the course "Methods of Upbringing". Its goal has been to improve evaluation of higher education teaching. Different forms…

  10. Higher-level Innovization

    DEFF Research Database (Denmark)

    Bandaru, Sunith; Tutum, Cem Celal; Deb, Kalyanmoy

    2011-01-01

    we introduce the higher-level innovization task through an application of a manufacturing process simulation for the Friction Stir Welding (FSW) process where commonalities among two different Pareto-optimal fronts are analyzed. Multiple design rules are simultaneously deciphered from each front...

  11. Benchmarking for Higher Education.

    Science.gov (United States)

    Jackson, Norman, Ed.; Lund, Helen, Ed.

    The chapters in this collection explore the concept of benchmarking as it is being used and developed in higher education (HE). Case studies and reviews show how universities in the United Kingdom are using benchmarking to aid in self-regulation and self-improvement. The chapters are: (1) "Introduction to Benchmarking" (Norman Jackson…

  12. Creativity in Higher Education

    Science.gov (United States)

    Gaspar, Drazena; Mabic, Mirela

    2015-01-01

    The paper presents results of research related to perception of creativity in higher education made by the authors at the University of Mostar from Bosnia and Herzegovina. This research was based on a survey conducted among teachers and students at the University. The authors developed two types of questionnaires, one for teachers and the other…

  13. California's Future: Higher Education

    Science.gov (United States)

    Johnson, Hans

    2015-01-01

    California's higher education system is not keeping up with the changing economy. Projections suggest that the state's economy will continue to need more highly educated workers. In 2025, if current trends persist, 41 percent of jobs will require at least a bachelor's degree and 36 percent will require some college education short of a bachelor's…

  14. Cyberbullying in Higher Education

    Science.gov (United States)

    Minor, Maria A.; Smith, Gina S.; Brashen, Henry

    2013-01-01

    Bullying has extended beyond the schoolyard into online forums in the form of cyberbullying. Cyberbullying is a growing concern due to the effect on its victims. Current studies focus on grades K-12; however, cyberbullying has entered the world of higher education. The focus of this study was to identify the existence of cyberbullying in higher…

  15. Teenage Smoking: Higher Excise Tax Should Significantly Reduce the Number of Smokers

    Science.gov (United States)

    1989-06-30

    12 to 17, in the United States, about 3.5 million use tobacco products, almost 3 million smoke marijuana , 6 million drink alcohol, and 1 million use...particularly in indoor environments. As a result nonsmokers tend to face a greater risk of cancer and of becoming less healthy in general. (The details on

  16. Knowing Feminism: The Significance of Higher Education to Women's Narratives of "Becoming Feminist"

    Science.gov (United States)

    Guest, Carly Joanne

    2016-01-01

    Educational spaces have long provided opportunities for politicisation and activism. However, research into the processes through which students become politicised can often focus on participation in recognised forms of political action, thereby ignoring the multiple factors active in developing a political consciousness. This paper draws on…

  17. Competitiveness - higher education

    Directory of Open Access Journals (Sweden)

    Labas Istvan

    2016-03-01

    Full Text Available Involvement of European Union plays an important role in the areas of education and training equally. The member states are responsible for organizing and operating their education and training systems themselves. And, EU policy is aimed at supporting the efforts of member states and trying to find solutions for the common challenges which appear. In order to make our future sustainable maximally; the key to it lies in education. The highly qualified workforce is the key to development, advancement and innovation of the world. Nowadays, the competitiveness of higher education institutions has become more and more appreciated in the national economy. In recent years, the frameworks of operation of higher education systems have gone through a total transformation. The number of applying students is continuously decreasing in some European countries therefore only those institutions can “survive” this shortfall, which are able to minimize the loss of the number of students. In this process, the factors forming the competitiveness of these budgetary institutions play an important role from the point of view of survival. The more competitive a higher education institution is, the greater the chance is that the students would like to continue their studies there and thus this institution will have a greater chance for the survival in the future, compared to ones lagging behind in the competition. Aim of our treatise prepared is to present the current situation and main data of the EU higher education and we examine the performance of higher education: to what extent it fulfils the strategy for smart, sustainable and inclusive growth which is worded in the framework of Europe 2020 programme. The treatise is based on analysis of statistical data.

  18. Determination of L-AP4-bound human mGlu8 receptor amino terminal domain structure and the molecular basis for L-AP4’s group III mGlu receptor functional potency and selectivity

    Energy Technology Data Exchange (ETDEWEB)

    Schkeryantz, Jeffery M.; Chen, Qi; Ho, Joseph D.; Atwell, Shane; Zhang, Aiping; Vargas, Michelle C.; Wang, Jing; Monn, James A.; Hao, Junliang (Lilly)

    2018-02-01

    Here, L-2-Amino-4-phosphonobutyric acid (L-AP4) is a known potent and selective agonist for the Group III mGlu receptors. However, it does not show any selectivity among the individual group III mGlu subtypes. In order to understand the molecular basis for this group selectivity, we solved the first human mGlu8 amino terminal domain (ATD) crystal structures in complex with L-glu and L-AP4. In comparison with other published L-glu-bound mGlu ATD structures, we have observed L-glu binds in a significantly different manner in mGlu1. Furthermore, these new structures provided evidence that both the electronic and steric nature of the distal phosphate of L-AP4 contribute to its exquisite Group III functional agonist potency and selectivity.

  19. 1,3-Oxazole-based selective picomolar inhibitors of cytosolic human carbonic anhydrase II alleviate ocular hypertension in rabbits: Potency is supported by X-ray crystallography of two leads.

    Science.gov (United States)

    Ferraroni, Marta; Lucarini, Laura; Masini, Emanuela; Korsakov, Mikhail; Scozzafava, Andrea; Supuran, Claudiu T; Krasavin, Mikhail

    2017-09-01

    Two lead 1,3-oxazole-based carbonic anhydrase inhibitors (CAIs) earlier identified as selective, picomolar inhibitors of hCA II (a cytosolic target for treatment of glaucoma) have been investigated further. Firstly, they were found to be conveniently synthesized on multigram scale, which enables further development. These compounds were found to be comparable in efficacy to dorzolamide eye drops when applied in the eye drop form as well. Finally, the reasons for unusually high potency of these compounds became understood from their high-resolution X-ray crystallography structures. These data significantly expand our understanding of heterocycle-based primary sulfonamides, many of which have recently emerged from our labs - particularly, from the corneal permeability standpoint. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Phytoalexin Elicitation- Potency As A Novel Technology for Biological Control and Protection Digitalis purpurea L. plants from Pre-Sowing Seed Treatment with Gamma Ray and Electric Current

    International Nuclear Information System (INIS)

    Bosila, H.A.; Lila, M.; Ahmed, T.E.S.

    2012-01-01

    Digitalis purpurea L seeds treated with gamma ray, (G) 0, 2.5, 5, 7.5 KR, and electric current (E), 0, 100, 150, 200 mA, then planted in splite-splite plot design for 3 replicates (R) and 2 successive seasons, in sandy soil irrigated with brackish water (900ppm) through surface drip irrigation system (SDI).The formed plants were foliar sprayed with manganese (M),0,3ppm-The formed Phytoalexin (PA) was bioassayed and chemically quantified.M3ppm could induce sistemic resistance (ISR) which initiate to farm 0.064, 0.070 mg PA 100mg fresh leaves. The formed PA exhibited PA-glycosidal structure wherefore, achieve therapeutic potency. (G) depress significantlly PA 73-91% of control while (E) activated (PA) significantly 134-154% of control. At (GE) interaction, such (G) dose PA increased significantlly by increasing (E) dose up to E200mA. Hence (E) efface a serious depression of (G). At (GEM) interaction, (G) 2.5, 5, 7.5 KR EO mA, M3ppm the formed. (PA) were; 91, 75, 63 were increased significantlly by increasing (E) dose up to E200mA M3ppm 128, 119, 109 – 129, 117, 107% of control for first and second season, respectively. Therefore, M elicitor application, in GEM combination, could be considered as a novel strategy for biological control and plant protection, from economic and environmental benefit point of view. It would occur by decreasing the cost of fungicides, bactericides and pesticides in Digitalis purpurea L biomass production, grown in extended agriculture area.

  1. Use of In Vivo and In Vitro Data to Derive a Chronic Reference Value for Crotonaldehyde Based on Relative Potency to Acrolein.

    Science.gov (United States)

    Grant, Roberta L; Jenkins, Allison F

    2015-01-01

    The Texas Commission on Environmental Quality (TCEQ) conducted a chronic inhalation noncancer toxicity assessment for crotonaldehyde (CRO). Since there were limited toxicity data for CRO, a reference value (ReV) was derived using a relative potency factor (RPF) approach with acrolein as the index chemical. Both CRO and acrolein are α,β-unsaturated carbonyls and share common steps in their mode of action (MOA). Only studies that investigated the effects of CRO and acrolein in the same study were used to calculate a CRO:acrolein RPF. In vivo findings measuring both 50% respiratory depression in rats and two species of mice and subcutaneous 50% lethality in rats and mice were used to calculate an RPF of 3 (rounded to one significant figure). In vitro data were useful to compare the MOA of CRO and acrolein and to support the RPF determined using in vivo data. In vitro cell culture studies investigating cytotoxicity in normal human lung fibroblast cultures using the propidium iodide cytotoxicity assay and in mouse lymphocyte cultures using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay were used to calculate an in vitro RPF of 3, which supports the in vivo RPF. The chronic ReV for acrolein of 1.2 ppb derived by TCEQ was multiplied by the RPF of 3 to calculate the ReV for CRO of 3.6 ppb (10 μg/m(3)). The ReV for CRO was developed to protect the general public from adverse health effects from chronic exposure to CRO in ambient air.

  2. Disturbances of ligand potency and enhanced degradation of the human glycine receptor at affected positions G160 and T162 originally identified in patients suffering from hyperekplexia

    Directory of Open Access Journals (Sweden)

    Sinem eAtak

    2015-12-01

    Full Text Available Ligand-binding of Cys-loop receptors is determined by N-terminal extracellular loop structures from the plus as well as from the minus side of two adjacent subunits in the pentameric receptor complex. An aromatic residue in loop B of the glycine receptor (GlyR undergoes direct interaction with the incoming ligand via cation-π interactions. Recently we showed that mutated residues in loop B identified from human patients suffering from hyperekplexia disturb ligand-binding. Here, we exchanged the affected human residues by amino acids found in related members of the Cys-loop receptor family to determine the effects of side chain volume for ion channel properties. GlyR variants were characterized in vitro following transfection into cell lines in order to analyze protein expression, trafficking, degradation and ion channel function. GlyR α1 G160 mutations significantly decrease glycine potency arguing for a positional effect on neighboring aromatic residues and consequently glycine-binding within the ligand-binding pocket. Disturbed glycinergic inhibition due to T162 α1 mutations is an additive effect of affected biogenesis and structural changes within the ligand-binding site. Protein trafficking from the ER towards ER-Golgi intermediate compartment, the secretory Golgi pathways and finally the cell surface is largely diminished, but still sufficient to deliver ion channels that are functional at least at high glycine concentrations. The majority of T162 mutant protein accumulates in the ER and is conducted to ER-associated proteasomal degradation. Hence, G160 is an important determinant during glycine binding. In contrast, T162 assigns primarily receptor biogenesis whereas exchanges in functionality are secondary effects thereof.

  3. Extracellular ionic locks determine variation in constitutive activity and ligand potency between species orthologs of the free fatty acid receptors FFA2 and FFA3

    DEFF Research Database (Denmark)

    Hudson, Brian D; Tikhonova, Irina G; Pandey, Sunil K

    2012-01-01

    Free fatty acid receptors 2 and 3 (FFA2 and FFA3) are G protein-coupled receptors for short chain free fatty acids (SCFAs). They respond to the same set of endogenous ligands but with distinct rank-order of potency such that acetate (C2) has been described as FFA2-selective, whereas propionate (C...

  4. High Efficacy but Low Potency of delta-Opioid Receptor-G Protein Coupling in Brij-58-Treated, Low-Density Plasma Membrane Fragments

    Czech Academy of Sciences Publication Activity Database

    Roubalová, Lenka; Vošahlíková, Miroslava; Brejchová, Jana; Sýkora, Jan; Rudajev, Vladimír; Svoboda, Petr

    2015-01-01

    Roč. 10, č. 8 (2015), e0135664 E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GAP207/12/0919 Institutional support: RVO:67985823 ; RVO:61388955 Keywords : delta - opioid receptor * G protein coupling * detergent * efficacy * potency Subject RIV: CE - Biochemistry; CF - Physical ; Theoretical Chemistry (UFCH-W) Impact factor: 3.057, year: 2015

  5. Recombinant pediocin in Lactococcus lactis : increased production by propeptide fusion and improved potency by co-production with PedC

    NARCIS (Netherlands)

    Back, Alexandre; Borges, Frederic; Mangavel, Cecile; Paris, Cedric; Rondags, Emmanuel; Kapel, Romain; Aymes, Arnaud; Rogniaux, Helene; Pavlovic, Marija; van Heel, Auke J.; Kuipers, Oscar P.; Revol-Junelles, Anne-Marie; Cailliez-Grimal, Catherine

    We describe the impact of two propeptides and PedC on the production yield and the potency of recombinant pediocins produced in Lactococcus lactis. On the one hand, the sequences encoding the propeptides SD or LEISSTCDA were inserted between the sequence encoding the signal peptide of Usp45 and the

  6. Multi-Level Analysis of Peer Support, Internet Self-Efficacy and E-Learning Outcomes--The Contextual Effects of Collectivism and Group Potency

    Science.gov (United States)

    Chu, Regina Juchun; Chu, Anita Zichun

    2010-01-01

    The present study intends to explore the role of collectivism and group potency at group level in predicting individual Internet self-efficacy (ISE) and individual e-learning outcomes for people aged over 45. Group learning has been widely discussed in the research into online formats. However, less study has been carried out about how…

  7. A small-volume bioassay for quantification of the esterase inhibiting potency of mixtures of organophosphate and carbamate insecticides in rainwater : development and optimization

    NARCIS (Netherlands)

    Hamers, T.; Molin, K.R.J.; Koeman, J.H.; Murk, A.J.

    2000-01-01

    The goal of this study was to develop a sensitive in vitro bioassay for quantification of the total esterase inhibiting potency of low concentrations of organophosphate and carbamate insecticides in relatively small rainwater samples. Purified acetylcholinesterase (AChE) from electric eel

  8. An International Standard for specifying the minimum potency of anti-D blood-grouping reagents: evaluation of a candidate preparation in an international collaborative study

    NARCIS (Netherlands)

    Thorpe, S. J.; Fox, B.; Heath, A. B.; Scott, M.; de Haas, M.; Kochman, S.; Padilla, A.

    2006-01-01

    The aim of this study was to evaluate a lyophilized monoclonal immunoglobulin M (IgM) anti-D preparation for use as an International Standard to specify a recommended minimum acceptable potency of anti-D blood-grouping reagents. The candidate International Standard (99/836) for specifying the

  9. An investigation to evaluate the analgesic and central nervous system depressant activities of Solanum nigrum (Linn. in Homoeopathic potencies in experimental animal models

    Directory of Open Access Journals (Sweden)

    Echur Natarajan Sundaram

    2015-01-01

    Full Text Available Background and Objective: In Homoeopathy, Solanum nigrum is clinically used in the treatment of ergotism, meningitis, irritation during dentition and some of the symptoms of neurological disorders but its Central Nervous System (CNS potential has not been explored experimentally yet. Therefore, a preliminary study was conducted with an objective to evaluate the analgesic and CNS depressant effects of homoeopathic potencies of S. nigrum in experimental animal models. Materials and Methods: The study was conducted in Wistar albino rats using a hot plate, ice plate and Randall-Selitto assay for analgesic; rota-rod and open field test for CNS depressant activities. The different potencies (3X, 6X, 12X and 30C of Solanum nigrum were administered orally (0.5 ml/rat/day for 30 days and response was assessed after 30 minutes of drug administration on 10 th , 20 th and 30 th day. Results: The result shows that all the four potencies of Solanum nigrum has increased the latency time required to raise and lick the paws for thermal sensation on hot plate test and for cold sensation on ice plate test and also increased the degree of threshold pressure to mechanically induced pain on Randall-Selitto assay but depressed the motor coordination and locomotor activities. Conclusion: The result obtained from this preliminary study suggests that homoeopathic preparation of Solanum nigrum in different potencies possess analgesic and CNS depressant activities. Further detailed investigations are required for its possible human use.

  10. Skin sensitization potency of methyl methacrylate in the local lymph node assay: comparisons with guinea-pig data and human experience.

    Science.gov (United States)

    Betts, Catherine J; Dearman, Rebecca J; Heylings, Jon R; Kimber, Ian; Basketter, David A

    2006-09-01

    There is compelling evidence that contact allergens differ substantially (by 4 or 5 orders of magnitude) with respect to their inherent skin-sensitizing potency. Relative potency can now be measured effectively using the mouse local lymph node assay (LLNA) and such data form the basis of risk assessment and risk management strategies. Such determinations also facilitate distinctions being drawn between the prevalence of skin sensitization to a particular contact allergen and inherent potency. The distinction is important because chemicals that are implicated as common causes of contact allergy are not necessarily potent sensitizers. One example is provided by nickel that is undoubtedly a common cause of allergic contact dermatitis, but is a comparatively weak sensitizer in predictive tests. In an attempt to explore other examples of contact allergens where there may exist a discrepancy between prevalence and potency, we describe here analyses conducted with methyl methacrylate (MMA). Results of LLNA studies have been interpreted in the context of historical clinical data on occupational allergic contact dermatitis associated with exposure to MMA.

  11. Impact of viral enhancin genes on potency of Lymantria dispar multiple nucleopolyhedrovirus in L. dispar following disruption of the peritrophic matrix

    Science.gov (United States)

    Kelli Hoover; Merideth A. Humphries; Alyssa R. Genfron; James M. Slavicek

    2010-01-01

    Enhancins are metalloproteases found in many betabaculoviruses and several alphabaculoviruses, which enhance alphabaculovirus potency by degrading a protein component of the peritrophic matrix (PM), facilitating passage of virions through this structure. Earlier studies on betabaculovirus enhancins within heterologous systems suggested that enhancins facilitate virion...

  12. An exceptionally potent inducer of cytoprotective enzymes: elucidation of the structural features that determine inducer potency and reactivity with Keap1.

    Science.gov (United States)

    Dinkova-Kostova, Albena T; Talalay, Paul; Sharkey, John; Zhang, Ying; Holtzclaw, W David; Wang, Xiu Jun; David, Emilie; Schiavoni, Katherine H; Finlayson, Stewart; Mierke, Dale F; Honda, Tadashi

    2010-10-29

    The Keap1/Nrf2/ARE pathway controls a network of cytoprotective genes that defend against the damaging effects of oxidative and electrophilic stress, and inflammation. Induction of this pathway is a highly effective strategy in combating the risk of cancer and chronic degenerative diseases, including atherosclerosis and neurodegeneration. An acetylenic tricyclic bis(cyano enone) bearing two highly electrophilic Michael acceptors is an extremely potent inducer in cells and in vivo. We demonstrate spectroscopically that both cyano enone functions of the tricyclic molecule react with cysteine residues of Keap1 and activate transcription of cytoprotective genes. Novel monocyclic cyano enones, representing fragments of rings A and C of the tricyclic compound, reveal that the contribution to inducer potency of the ring C Michael acceptor is much greater than that of ring A, and that potency is further enhanced by spatial proximity of an acetylenic function. Critically, the simultaneous presence of two cyano enone functions in rings A and C within a rigid three-ring system results in exceptionally high inducer potency. Detailed understanding of the structural elements that contribute to the reactivity with the protein sensor Keap1 and to high potency of induction is essential for the development of specific and selective lead compounds as clinically relevant chemoprotective agents.

  13. Establishment of the relative antiinflammatory potency of deflazacort and prednisone in polymyalgia rheumatica

    DEFF Research Database (Denmark)

    Lund, B; Egsmose, C; Jørgensen, S

    1987-01-01

    following prednisone treatment. Subsequently, in a similar regimen, prednisone was compared with deflazacort at a weight ratio of 1:1.2 in 10 patients, 1:1.5 in another 10 patients, and 1:1.8 in still another 10 patients for purposes of dose titration. Again, significant rises were seen in ESR, plasma...

  14. Synthesis and SAR of novel imidazoquinoxaline-based Lck inhibitors: improvement of cell potency.

    Science.gov (United States)

    Chen, Ping; Iwanowicz, Edwin J; Norris, Derek; Gu, Henry H; Lin, James; Moquin, Robert V; Das, Jagabandhu; Wityak, John; Spergel, Steven H; de Fex, Henry; Pang, Suhong; Pitt, Sydney; Shen, Ding Ren; Schieven, Gary L; Barrish, Joel C

    2002-11-04

    A series of anilino(imidazoquinoxaline) analogues bearing solubilizing side chains at the 6- and 7-positions of the fused phenyl ring has been prepared and evaluated for inhibition against Lck enzyme and of T-cell proliferation. Significant improvement of the cellular activity was achieved over the initial lead, compound 2.

  15. Higher Education Language Policy

    DEFF Research Database (Denmark)

    Lauridsen, Karen M.

    2013-01-01

    Summary of recommendations HEIs are encouraged, within the framework of their own societal context, mission, vision and strategies, to develop the aims and objectives of a Higher Education Language Policy (HELP) that allows them to implement these strategies. In this process, they may want......: As the first step in a Higher Education Language Policy, HEIs should determine the relative status and use of the languages employed in the institution, taking into consideration the answers to the following questions:  What is/are the official language(s) of the HEI?  What is/are the language...... and the level of internationalisation the HEI has or wants to have, and as a direct implication of that, what are the language proficiency levels expected from the graduates of these programme?  Given the profile of the HEI and its educational strategies, which language components are to be offered within...

  16. Influence of gamma rays radiation on lignin degradation potency of phanerochaete chrysosporium and ganoderma lucidum

    International Nuclear Information System (INIS)

    Tri Retno DL; Nana Mulyana; Nurhasni; Uswatun Hasanah

    2016-01-01

    This research aims to increase the activity of extracellular enzymes lignolitik fungi phanerochaete chrysosporium and ganoderma lucidum to degrade lignocellulosic waste. Lignocellulosic difficult to degrade because it is composed of lignin, cellulose and hemicellulose. Phanerochaete chrysosporium and ganoderma lucidum group white rot fungi can degrade lignin because it is able to synthesize enzymes lignin peroxidase (LiP). Irradiation low dose gamma rays capable menstimulsi increase extracellular enzyme activity. Fungi phanerochaete chrysosporium and ganoderma lucidum in medium slent exposed to gamma irradiation at doses of 0 (control), 200, 400, 600, 800 and 1000 Gy. In a liquid medium containing Potatoes Dextrose Broth (PDB), mineral salts with the substrate lignin alkali 0 and 5 % w/v, fungi phanerochaete chrysosporium were exposed to a dose of 600 Gy of gamma rays have LiP activity (30 U/mL) by 2.5 times higher compared with controls (12 U/mL). While ganoderma lucidum that are exposed to gamma radiation at a dose of 800 Gy has LiP activity (34 U/mL) was 1.7 times higher than the control (20 U/mL). On a solid substrate fermentation of white teak powder (Gmelina arborea Roxb.) For 12 days at pH 6.4 and water content of 79 % by fungi phanerochaete chrysosporium were exposed to gamma ray dose of 600 Gy has an efficiency of lignin degradation by 42 %, whereas on fungi ganoderma lucidum that are exposed gamma ray dose of 800 Gy has an efficiency of lignin degradation by 21 % with optimal conditions of pH 7. And; water content of 71.3 %. (author)

  17. Novel approach for classifying chemicals according to skin sensitizing potency by non-radioisotopic modification of the local lymph node assay.

    Science.gov (United States)

    Takeyoshi, Masahiro; Iida, Kenji; Shiraishi, Keiji; Hoshuyama, Satsuki

    2005-01-01

    The murine local lymph node assay (LLNA) is currently recognized as a stand-alone sensitization test for determining the sensitizing potential of chemicals, and it has the advantage of yielding a quantitative endpoint that can be used to predict the sensitization potency of chemicals. The EC3 has been proposed as a parameter for classifying chemicals according to the sensitization potency. We previously developed a non-radioisotopic endpoint for the LLNA based on 5-bromo-2'-deoxyuridine (BrdU) incorporation (non-RI LLNA), and we are proposing a new procedure to predict the sensitization potency of chemicals based on comparisons with known human contact allergens. Nine chemicals (i.e. diphencyclopropenone, p-phenylenediamine, glutaraldehyde, cinnamicaldehyde, citral, eugenol, isopropyl myristate, propyleneglycol and hexane) categorized as human contact allergen classes 1-5 were tested by the non-RI LLNA with the following reference allergens: 2,4-dinitrochlorobenzene (DNCB) as a class 1 human contact allergen, isoeugenol as a class 2 human contact allergen and alpha-hexylcinnamic aldehyde (HCA) as a class 3 human contact allergen. Consequently, nine test chemicals were almost assigned to their correct allergen class. The results suggested that the new procedure for non-RI LLNA can provide correct sensitization potency data. Sensitization potency data are useful for evaluating the sensitization risk to humans of exposure to new chemical products. Accordingly, this approach would be an effective modification of LLNA with regard to its experimental design. Moreover, this procedure can be applied also to the standard LLNA with radioisotopes and to other modifications of the LLNA. Copyright 2005 John Wiley & Sons, Ltd.

  18. Sensor potency of the moonlighting enzyme-decorated cytoskeleton: the cytoskeleton as a metabolic sensor

    Science.gov (United States)

    2013-01-01

    Background There is extensive evidence for the interaction of metabolic enzymes with the eukaryotic cytoskeleton. The significance of these interactions is far from clear. Presentation of the hypothesis In the cytoskeletal integrative sensor hypothesis presented here, the cytoskeleton senses and integrates the general metabolic activity of the cell. This activity depends on the binding to the cytoskeleton of enzymes and, depending on the nature of the enzyme, this binding may occur if the enzyme is either active or inactive but not both. This enzyme-binding is further proposed to stabilize microtubules and microfilaments and to alter rates of GTP and ATP hydrolysis and their levels. Testing the hypothesis Evidence consistent with the cytoskeletal integrative sensor hypothesis is presented in the case of glycolysis. Several testable predictions are made. There should be a relationship between post-translational modifications of tubulin and of actin and their interaction with metabolic enzymes. Different conditions of cytoskeletal dynamics and enzyme-cytoskeleton binding should reveal significant differences in local and perhaps global levels and ratios of ATP and GTP. The different functions of moonlighting enzymes should depend on cytoskeletal binding. Implications of the hypothesis The physical and chemical effects arising from metabolic sensing by the cytoskeleton would have major consequences on cell shape, dynamics and cell cycle progression. The hypothesis provides a framework that helps the significance of the enzyme-decorated cytoskeleton be determined. PMID:23398642

  19. Shared Leadership Transforms Higher Education IT

    Science.gov (United States)

    Duin, Ann Hill; Cawley, Steve; Gulachek, Bernard; O'Sullivan, Douglas M.; Wollner, Diane

    2011-01-01

    Globalization, immersive research and learning environments, unlimited access to information and analytics, and fiscal realities continue to impact higher education--and higher education IT. Although IT organizations face immense pressure to meet significantly greater expectations at significantly less cost, with such pressure comes the…

  20. Higher Education in Scandinavia

    DEFF Research Database (Denmark)

    Nielsen, Jørgen Lerche; Andreasen, Lars Birch

    2015-01-01

    Higher education systems around the world have been undergoing fundamental changes through the last 50 years from more narrow self-sustaining universities for the elite and into mass universities, where new groups of students have been recruited and the number of students enrolled has increased...... an impact on the educational systems in Scandinavia, and what possible futures can be envisioned?...... dramatically. In adjusting to the role of being a mass educational institution, universities have been challenged on how to cope with external pressures, such as forces of globalization and international markets, increased national and international competition for students and research grants, increased...

  1. Higher engineering mathematics

    CERN Document Server

    John Bird

    2014-01-01

    A practical introduction to the core mathematics principles required at higher engineering levelJohn Bird's approach to mathematics, based on numerous worked examples and interactive problems, is ideal for vocational students that require an advanced textbook.Theory is kept to a minimum, with the emphasis firmly placed on problem-solving skills, making this a thoroughly practical introduction to the advanced mathematics engineering that students need to master. The extensive and thorough topic coverage makes this an ideal text for upper level vocational courses. Now in

  2. Potency of Garlic Extract Against Koi Herpesvirus (KHV in Common Carp

    Directory of Open Access Journals (Sweden)

    Sri Nuryati

    2007-07-01

    Full Text Available Prevention of koi herpesvirus (KHV infection using chemicals or medicines was ineffective way.  In this study garlic extract was used to prevent KHV infection.  Virus suspension of 0.1 ml and garlic extract of 0.1 ml in different dosage, i.e., 100, 200 and 300 ppt, was injected into common carp body.  Hemoglobin concentration, red and white blood cell numbers, and leukocyte number were counted.  The results of study showed that administration of 300 ppt of garlic extract could produce higher survival rate (67.5%, good blood parameters and clinical symptoms compared to other treatments. Keywords: garlic, KHV, common carp   ABSTRAK Upaya penanggulangan wabah Koi Herpesvirus (KHV menggunakan bahan-bahan kimia atau obat-obatan adalah tidak efektif. Pada penelitian ini dilakukan pemberian ekstrak bawang putih untuk menanggulangi infeksi KHV.  Suspensi virus sebanyak 0,1 ml ditambahkan dengan 0,1 ml ekstrak bawang putih dengan berbagai konsentrasi, yaitu 100, 200 dan 300 ppt, disuntikkan ke dalam tubuh ikan mas.  Kadar hemoglobin, jumlah sel darah merah dan sel darah putih jenis dan jumlah leukosit diamati. Hasil penelitian menunjukkan bahwa pemberian ekstrak bawang putih sebanyak 300 ppt menghasilkan kelangsungan hidup (67,5% yang lebih baik dibandingkan dengan perlakuan lainnya, dan begitu pula dengan gambaran darah serta gejala klinisnya.   Kata kunci: bawang putih, KHV, ikan mas

  3. Ethical Leadership and Reporting of Ethical Problems: The Roles of Moral Potency and Moral Identity%伦理型领导与伦理问题报告:道德效力与道德认同的作用

    Institute of Scientific and Technical Information of China (English)

    章发旺; 廖建桥

    2017-01-01

    组织中的非伦理行为不仅普遍存在而且具有隐蔽性,鼓励员工报告身边的伦理问题成为组织强化伦理管理的重要方式.基于社会学习理论和道德意动能力视角,探讨伦理型领导对员工伦理问题报告的影响,尤其是道德效力在二者间的中介作用与道德认同的调节效应.采用两阶段问卷调查方式收集多个企业的326名员工样本,运用层级线性回归和Bootstrapping方法对假设进行检验.结果显示,伦理型领导显著正向影响员工的伦理问题报告,道德效力在二者间起部分中介作用.当员工的道德认同较高时,伦理型领导对伦理问题报告具有更强的正向作用;当员工的道德认同较低时,伦理型领导对道德效力具有更强的正向影响,并且通过道德效力对伦理问题报告的间接作用更强.研究结果为理解伦理型领导如何激发员工报告伦理问题提供了新的视角,对于加强组织的伦理管理具有重要的现实意义.%Given the prevalence and concealment of unethical behaviors in organizations,reporting of ethical problems to management represents an important ethical management resource for organizations.Based on social learning theory and moral conation perspective,we examine the relationship between ethical leadership and followers' reporting of ethical problems,and especially explore the mediating role of moral potency and the moderating effect of moral identity between them.Through a two-stage survey-based study of 326 employees in multiple organizations,hierarchical regression analysis and bootstrap are applied to test our hypotheses.The results reveal that ethical leadership has a positive effect on employees' reporting of ethical problems and moral potency partially mediates the relationship between the two.When employee has higher moral identity,ethical leadership is more positively related to reporting of ethical problems.For the employee with low moral identity

  4. The Potency of Bixa orellana Seedcouts Extract’s as Antiimflamation Drug

    Directory of Open Access Journals (Sweden)

    Atina Hussaana

    2012-12-01

    Design and Method: This study was post test only control group design. Twenty four mice is selected randomly then divided into four groups, KI (extract 0.09 mg, K.II (extract 0.18 mg dose, K.III (aspirin 90 mg, and K.IV (CMCNa 0.125%. Oedema volume was measured before injection karagenin 1%, two, 2.5, three and four hours after injection karagenin. The mean reduction in inflammation were tested by one way anova and pos hoc LSD. Result: Greatest reduction in inflammation indicated by K.III (0.100 ml, then in K.II (0.067 ml, KI (0.072 ml, and lowest in K.IV (-0.017 ml. Differences in the reduction of inflammation significantly different between KI and K.II K.IV; and K.III whereas no significant difference was found between KI and K.III K.II. Conclusion: The extract of the outer seed coats of annatto (Bixa orellana L. have antiimflamantory activity in mice that was induced by karagenin 1% (Sains Medika, 4(2:134-141.

  5. Selenazolinium Salts as “Small Molecule Catalysts” with High Potency against ESKAPE Bacterial Pathogens

    Directory of Open Access Journals (Sweden)

    Karolina Witek

    2017-12-01

    Full Text Available In view of the pressing need to identify new antibacterial agents able to combat multidrug-resistant bacteria, we investigated a series of fused selenazolinium derivatives (1–8 regarding their in vitro antimicrobial activities against 25 ESKAPE-pathogen strains. Ebselen was used as reference compound. Most of the selenocompounds demonstrated an excellent in vitro activity against all S. aureus strains, with activities comparable to or even exceeding the one of ebselen. In contrast to ebselen, some selenazolinium derivatives (1, 3, and 7 even displayed significant actions against all Gram-negative pathogens tested. The 3-bromo-2-(1-hydroxy-1-methylethyl[1,2]selenazolo[2,3-a]pyridinium chloride (1 was particularly active (minimum inhibitory concentrations, MICs: 0.31–1.24 µg/mL for MRSA, and 0.31–2.48 µg/mL for Gram-negative bacteria and devoid of any significant mutagenicity in the Ames assay. Our preliminary mechanistic studies in cell culture indicated that their mode of action is likely to be associated with an alteration of intracellular levels of glutathione and cysteine thiols of different proteins in the bacterial cells, hence supporting the idea that such compounds interact with the intracellular thiolstat. This alteration of pivotal cysteine residues is most likely the result of a direct or catalytic oxidative modification of such residues by the highly reactive selenium species (RSeS employed.

  6. Low Potency Homeopathic Remedies and Allopathic Herbal Medicines: Is There an Overlap?

    Science.gov (United States)

    Csupor, Dezső; Boros, Klára; Hohmann, Judit

    2013-01-01

    Classical homeopathy is based on the therapeutic application of highly diluted homeopathic stocks. The indications of such medicines are determined by proving, i.e. by applying the remedies in healthy subjects. However, there are several complex homeopathic medicinal products on the market with approved therapeutic indications. The efficacy of these medicines has been assessed in clinical trials on patients. There is no upper limit of dosing for such homeopathic remedies, and these products often contain undiluted mother tincture. The aim of our study was to compare an allopathic herbal medicine and a homeopathic product containing undiluted mother tincture based on the same plant. Two products (an allopathic herbal medicine and a homeopathic product) containing Vitex agnus-castus extract were analyzed by HPLC-DAD for their agnuside and casticin contents. The agnuside content of the allopathic product was approximately four times higher, while the amount of casticin was in the same order of magnitude. Our experiments revealed the presence of active ingredients in allopathic quantity in a homeopathic preparation, highlighting the controversy between the principles of classical and practice of contemporary homeopathy. According to the principles of classical homeopathy these remedies cannot be considered as homeopathic remedies but rather as (allopathic) herbal ones. This phenomenon necessitates a case-by-case approach towards the possible adverse effects and drug interactions of homeopathics in the daily medical practice. Homeopathic products containing active agents in allopathic doses should be treated the same way as allopathic medicines from the point of view of quality assurance and pharmacovigilance. PMID:24019954

  7. Low potency homeopathic remedies and allopathic herbal medicines: is there an overlap?

    Directory of Open Access Journals (Sweden)

    Dezső Csupor

    Full Text Available Classical homeopathy is based on the therapeutic application of highly diluted homeopathic stocks. The indications of such medicines are determined by proving, i.e. by applying the remedies in healthy subjects. However, there are several complex homeopathic medicinal products on the market with approved therapeutic indications. The efficacy of these medicines has been assessed in clinical trials on patients. There is no upper limit of dosing for such homeopathic remedies, and these products often contain undiluted mother tincture. The aim of our study was to compare an allopathic herbal medicine and a homeopathic product containing undiluted mother tincture based on the same plant. Two products (an allopathic herbal medicine and a homeopathic product containing Vitex agnus-castus extract were analyzed by HPLC-DAD for their agnuside and casticin contents. The agnuside content of the allopathic product was approximately four times higher, while the amount of casticin was in the same order of magnitude. Our experiments revealed the presence of active ingredients in allopathic quantity in a homeopathic preparation, highlighting the controversy between the principles of classical and practice of contemporary homeopathy. According to the principles of classical homeopathy these remedies cannot be considered as homeopathic remedies but rather as (allopathic herbal ones. This phenomenon necessitates a case-by-case approach towards the possible adverse effects and drug interactions of homeopathics in the daily medical practice. Homeopathic products containing active agents in allopathic doses should be treated the same way as allopathic medicines from the point of view of quality assurance and pharmacovigilance.

  8. Cigarette Smoking Impairs Adipose Stromal Cell Vasculogenic Activity and Abrogates Potency to Ameliorate Ischemia.

    Science.gov (United States)

    Barwinska, Daria; Traktuev, Dmitry O; Merfeld-Clauss, Stephanie; Cook, Todd G; Lu, Hongyan; Petrache, Irina; March, Keith L

    2018-06-01

    Cigarette smoking (CS) adversely affects the physiologic function of endothelial progenitor, hematopoietic stem and progenitor cells. However, the effect of CS on the ability of adipose stem/stromal cells (ASC) to promote vasculogenesis and rescue perfusion in the context of ischemia is unknown. To evaluate this, ASC from nonsmokers (nCS-ASC) and smokers (CS-ASC), and their activity to promote perfusion in hindlimb ischemia models, as well as endothelial cell (EC) survival and vascular morphogenesis in vitro were assessed. While nCS-ASC improved perfusion in ischemic limbs, CS-ASC completely lost this therapeutic effect. In vitro vasculogenesis assays revealed that human CS-ASC and ASC from CS-exposed mice showed compromised support of EC morphogenesis into vascular tubes, and the CS-ASC secretome was less potent in supporting EC survival/proliferation. Comparative secretome analysis revealed that CS-ASC produced lower amounts of hepatocyte growth factor (HGF) and stromal cell-derived growth factor 1 (SDF-1). Conversely, CS-ASC secreted the angiostatic/pro-inflammatory factor Activin A, which was not detected in nCS-ASC conditioned media (CM). Furthermore, higher Activin A levels were measured in EC/CS-ASC cocultures than in EC/nCS-ASC cocultures. CS-ASC also responded to inflammatory cytokines with 5.2-fold increase in Activin A secretion, whereas nCS-ASC showed minimal Activin A induction. Supplementation of EC/CS-ASC cocultures with nCS-ASC CM or with recombinant vascular endothelial growth factor, HGF, or SDF-1 did not rescue vasculogenesis, whereas inhibition of Activin A expression or activity improved network formation up to the level found in EC/nCS-ASC cocultures. In conclusion, ASC of CS individuals manifest compromised in vitro vasculogenic activity as well as in vivo therapeutic activity. Stem Cells 2018;36:856-867. © 2018 AlphaMed Press.

  9. Teaching at higher levels

    Science.gov (United States)

    1998-11-01

    Undergraduate physics programmes for the 21st century were under discussion at a recent event held in Arlington, USA, open to two or three members of the physics faculties of universities from across the whole country. The conference was organized by the American Association of Physics Teachers with co-sponsorship from the American Institute of Physics, the American Physical Society and Project Kaleidoscope. Among the various aims were to learn about physics departments that have successfully revitalized their undergraduate physics programmes with innovative introductory physics courses and multi-track majors programmes. Engineers and life scientists were to be asked directly how physics programmes can better serve their students, and business leaders would be speaking on how physics departments can help to prepare their students for the diverse careers that they will eventually follow. It was planned to highlight ways that departments could fulfil their responsibilities towards trainee teachers, to identify the resources needed for revitalizing a department's programme, and to develop guidelines and recommendations for a funding programme to support collaborative efforts among physics departments for carrying out the enhancements required. More details about the conference can be found on the AAPT website (see http://www.aapt.org/programs/rupc.html). Meanwhile the UK's Higher Education Funding Council has proposed a two-pronged approach to the promotion of high quality teaching and learning, as well as widening participation in higher education from 1999-2000. A total of £60m should be available to support these initiatives by the year 2001-2002. As part of this scheme the Council will invite bids from institutions to support individual academics in enhancing learning and teaching, as well as in recognition of individual excellence. As with research grants, such awards would enable staff to pursue activities such as the development of teaching materials

  10. Osteochondritis Dissecans Lesions in Family Members: Does a Positive Family History Impact Phenotypic Potency?

    Science.gov (United States)

    Gornitzky, Alex L; Mistovich, R Justin; Atuahuene, Brittany; Storey, Eileen P; Ganley, Theodore J

    2017-06-01

    Although repetitive microtrauma and athletic overuse patterns are most commonly associated with osteochondritis dissecans (OCD), recent studies have identified a potential genetic predisposition for OCD. Several case series have documented family pedigrees that support autosomal-dominant inheritance, but the families in these studies were all selected as a result of unique histories that may not accurately represent OCD inheritance patterns at large. Because there has been little investigation beyond these case reports, we aimed to describe a broader, more representative pattern of OCD inheritance applicable to all affected patients. (1) What proportion of patients treated for OCD of the knee have one or more immediate and/or extended family members with a history of OCD lesions? (2) Do patients with more phenotypically potent lesions, which we defined as patients with bilateral OCD lesions or patients who have undergone multiple procedures for OCD, have a higher frequency of affected relatives than those with less potent lesions? This retrospective study queried patient databases, diagnosis codes (International Classification of Diseases, 9th Revision), and surgical logs at a regional, tertiary care children's hospital to identify all patients treated over a 10-year period (March 2004-March 2014) by the senior author for OCD of the knee. All patients aged 0-18 years at the time of diagnosis were included. At our institution, patients with intact lesions are treated with a trial of conservative therapy; conversely, patients with a break in the articular cartilage and/or loose fragments of bone/cartilage are treated surgically. There were no OCD-specific contraindications to surgery. This search identified 543 patients. After patient identification, a questionnaire was designed that asked for the number, age, and gender of all immediate family members and the history of OCD lesions in any family member (immediate or extended). For all positive family members

  11. Discovery of a new function of curcumin which enhances its anticancer therapeutic potency

    Science.gov (United States)

    Nagahama, Koji; Utsumi, Tomoya; Kumano, Takayuki; Maekawa, Saeko; Oyama, Naho; Kawakami, Junji

    2016-08-01

    Curcumin has received immense attention over the past decades because of its diverse biological activities and recognized as a promising drug candidate in a large number of diseases. However, its clinical application has been hindered due to extremely low aqueous solubility, chemical stability, and cellular uptake. In this study, we discovered quite a new function of curcumin, i.e. pH-responsive endosomal disrupting activity, derived from curcumin’s self-assembly. We selected anticancer activity as an example of biological activities of curcumin, and investigated the contribution of pH-responsive property to its anticancer activity. As a result, we demonstrated that the pH-responsive property significantly enhances the anticancer activity of curcumin. Furthermore, we demonstrated a utility of the pH-responsive property of curcumin as delivery nanocarriers for doxorubicin toward combination cancer therapy. These results clearly indicate that the smart curcumin assemblies act as promising nanoplatform for development of curcumin-based therapeutics.

  12. The Potency of Local Bacterial Isolates Encapsulated Within Sodium Alginate in Carbofuran Degradation

    Science.gov (United States)

    Priyani, Nunuk; Pratiwi, Dian; Suryanto, Dwi

    2018-03-01

    Research on the viability of bacteria encapsulated within sodium alginate and their potential in carbofuran degradation has been done. A total of 8 bacterial isolates have been isolated from slaughter house waste. A 100 ml of Bushnell-Hass Broth (BHB) medium containing 146.982 ppm of carbofuran was used as a medium. As much as 2 gr of beads which equal to 108cells.ml‑1 was inoculated into each medium culture and incubated for 15 days at ambient temperature and was shaken at 100 rpm. Analysis of carbofuran residues using High Performance Liquid Chromatography (HPLC) showed that the best 2 isolates, DN 1 and OR 2, were able to decrease carbofuran phenol concentration up to 30.37 % and 32.09% respectively compared to control. These results suggested that no significant different from the ability of free cell which decreased carbofuran phenol concentration up to 32.54% and 28.29%.

  13. Subeffective doses of dexketoprofen trometamol enhance the potency and duration of fentanyl antinociception

    Science.gov (United States)

    Gaitán, Gema; Herrero, Juan F

    2002-01-01

    The combination of classic non-steroidal antiinflammatory drugs (NSAIDs) with opiates induces more analgesia than the summed effect of each drug given separately. No studies have been performed using new generation NSAIDs and fentanyl nor on the duration of this effect. We have studied the analgesic effect of fentanyl alone and after the administration of subeffective doses of dexketoprofen trometamol in rat nociceptive responses. The responses were evoked by noxious mechanical stimulation and were recorded as single motor units in male Wistar rats anaesthetized with α-chloralose. The effective dose 50 (ED50) observed with fentanyl was 22.4±1.5 μg kg−1 and full recovery was apparent 20 min later. The administration of a total dose of 40 μg kg−1 of dexketoprofen trometamol did not induce any significant effect on the nociceptive responses. In the presence of dexketoprofen trometamol, the ED50 for fentanyl was 5 fold lower than before: 3.8±1.1 μg kg−1 and no significant recovery was observed 45 min later. The opioid antagonist naloxone (200 μg kg−1) did not reverse the effect, although in control experiments the same dose was able to prevent any action of fentanyl given alone. We conclude that the combination of fentanyl and subeffective doses of dexketoprofen trometamol induces a more potent and longer lasting analgesic effect than that observed with fentanyl alone, and that this is not an opioid mediated action. PMID:11815374

  14. Higher Order Mode Fibers

    DEFF Research Database (Denmark)

    Israelsen, Stine Møller

    This PhD thesis considers higher order modes (HOMs) in optical fibers. That includes their excitation and characteristics. Within the last decades, HOMs have been applied both for space multiplexing in optical communications, group velocity dispersion management and sensing among others......-radial polarization as opposed to the linear polarization of the LP0X modes. The effect is investigated numerically in a double cladding fiber with an outer aircladding using a full vectorial modesolver. Experimentally, the bowtie modes are excited using a long period grating and their free space characteristics...... and polarization state are investigated. For this fiber, the onset of the bowtie effect is shown numerically to be LP011. The characteristics usually associated with Bessel-likes modes such as long diffraction free length and selfhealing are shown to be conserved despite the lack of azimuthal symmetry...

  15. Spiky higher genus strings

    International Nuclear Information System (INIS)

    Ambjoern, J.; Bellini, A.; Johnston, D.

    1990-10-01

    It is clear from both the non-perturbative and perturbative approaches to two-dimensional quantum gravity that a new strong coupling regime is setting in at d=1, independent of the genus of the worldsheet being considered. It has been suggested that a Kosterlitz-Thouless (KT) phase transition in the Liouville theory is the cause of this behaviour. However, it has recently been pointed out that the XY model, which displays a KT transition on the plane and the sphere, is always in the strong coupling, disordered phase on a surface of constant negative curvature. A higher genus worldsheet can be represented as a fundamental region on just such a surface, which might seem to suggest that the KT picture predicts a strong coupling region for arbitrary d, contradicting the known results. We resolve the apparent paradox. (orig.)

  16. Direct analysis of prostaglandin-E2 and -D2 produced in an inflammatory cell reaction and its application for activity screening and potency evaluation using turbulent flow chromatography liquid chromatography-high resolution mass spectrometry.

    Science.gov (United States)

    Shin, Jeong-Sook; Peng, Lei; Kang, Kyungsu; Choi, Yongsoo

    2016-09-09

    Direct analysis of prostaglandin-E2 (PGE2) and -D2 (PGD2) produced from a RAW264.7 cell-based reaction was performed by liquid chromatography high-resolution mass spectrometry (LC-HRMS), which was online coupled with turbulent flow chromatography (TFC). The capability of this method to accurately measure PG levels in cell reaction medium containing cytokines or proteins as a reaction byproduct was cross-validated by two conventional methods. Two methods, including an LC-HRMS method after liquid-liquid extraction (LLE) of the sample and a commercial PGE2 enzyme-linked immunosorbent assay (ELISA), showed PGE2 and/or PGD2 levels almost similar to those obtained by TFC LC-HRMS over the reaction time after LPS stimulation. After the cross-validation, significant analytical throughputs, allowing simultaneous screening and potency evaluation of 80 natural products including 60 phytochemicals and 20 natural product extracts for the inhibition of the PGD2 produced in the cell-based inflammatory reaction, were achieved using the TFC LC-HRMS method developed. Among the 60 phytochemicals screened, licochalcone A and formononetin inhibited PGD2 production the most with IC50 values of 126 and 151nM, respectively. For a reference activity, indomethacin and diclofenac were used, measuring IC50 values of 0.64 and 0.21nM, respectively. This method also found a butanol extract of Akebia quinata Decne (AQ) stem as a promising natural product for PGD2 inhibition. Direct and accurate analysis of PGs in the inflammatory cell reaction using the TFC LC-HRMS method developed enables the high-throughput screening and potency evaluation of as many as 320 samples in less than 48h without changing a TFC column. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Historical Significant Volcanic Eruption Locations

    Data.gov (United States)

    Department of Homeland Security — A significant eruption is classified as one that meets at least one of the following criteriacaused fatalities, caused moderate damage (approximately $1 million or...

  18. Antitumoral, antioxidant, and antimelanogenesis potencies of Hawthorn, a potential natural agent in the treatment of melanoma.

    Science.gov (United States)

    Mustapha, Nadia; Mokdad-Bzéouich, Imèn; Maatouk, Mouna; Ghedira, Kamel; Hennebelle, Thierry; Chekir-Ghedira, Leila

    2016-06-01

    The lack of an efficient agent that does not have the disadvantage of low activity (kojic acid), high cytotoxicity, and mutagenicity (hydroquinone), poor skin penetration (arbutin), or low stability in formulation (glabridin) led us to continue our research on new antipigmentation/skin-lightening agents. Therefore, research of natural products that can modulate the metabolism of pigmentation is of great interest. Otherwise, malignant melanoma is one of the most aggressive forms of skin cancer, with high metastatic potential, and currently, there is no effective chemotherapy against invasive melanoma. Therefore, it is necessary to develop new drugs with potent activity and weak side effects against melanoma. The in-vitro anticancer effect of hawthorn was analyzed against B16F10 melanoma cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effect of isolated compounds from hawthorn on melanogenesis in B16F10 melanoma cells was investigated by measuring the amounts of melanin and tyrosinase spectrophotometrically at 475 nm. Balb/c mice models inoculated with B16F10 mouse tumor cells were used to evaluate the in-vivo antitumoral potential of hawthorn by assessing its effect on the growth of transplanted tumors. The antioxidant potential of tested samples was evaluated in B16F10 and primary human keratinocyte cells using a cellular antioxidant activity assay. Hawthorn tested samples inhibited effectively the growth of melanoma cells in vitro. Furthermore, it appears that tested samples from hawthorn reduced melanogenesis by inhibiting the tyrosinase activity of B16F10 cells in a dose-dependent manner. In-vivo studies showed that hawthorn total oligomer flavonoids extract treatment at a dose of 150 mg/kg body weight for 21 days in implanted tumor mice resulted in significant inhibition of the tumor growth volume and weight. In addition, tested samples showed significant cellular antioxidant capacity against the reactive oxygen species

  19. Bivalent Llama Single-Domain Antibody Fragments against Tumor Necrosis Factor Have Picomolar Potencies due to Intramolecular Interactions

    Directory of Open Access Journals (Sweden)

    Els Beirnaert

    2017-07-01

    Full Text Available The activity of tumor necrosis factor (TNF, a cytokine involved in inflammatory pathologies, can be inhibited by antibodies or trap molecules. Herein, llama-derived variable heavy-chain domains of heavy-chain antibody (VHH, also called Nanobodies™ were generated for the engineering of bivalent constructs, which antagonize the binding of TNF to its receptors with picomolar potencies. Three monomeric VHHs (VHH#1, VHH#2, and VHH#3 were characterized in detail and found to bind TNF with sub-nanomolar affinities. The crystal structures of the TNF–VHH complexes demonstrate that VHH#1 and VHH#2 share the same epitope, at the center of the interaction area of TNF with its TNFRs, while VHH#3 binds to a different, but partially overlapping epitope. These structures rationalize our results obtained with bivalent constructs in which two VHHs were coupled via linkers of different lengths. Contrary to conventional antibodies, these bivalent Nanobody™ constructs can bind to a single trimeric TNF, thus binding with avidity and blocking two of the three receptor binding sites in the cytokine. The different mode of binding to antigen and the engineering into bivalent constructs supports the design of highly potent VHH-based therapeutic entities.

  20. Potency of Centrocema pubescence, Calopogonium mucunoides, and Micania cordata for cleaning metal contaminants of gold mines waste

    Directory of Open Access Journals (Sweden)

    NURIL HIDAYATI

    2006-01-01

    Full Text Available Based on some findings that some plants are tolerant to contaminated media, this research was conducted to study more thoroughly about characters and potencies of some of them as hyperaccumulators. Three of the most tolerant plants were studied in this research i.e Centrocema pubescence, Calopogonium mucunoides,and Micania cordata. The plants were grown in different waste media, i.e. tailing from PT. Aneka Tambang (ANTAM and people mine waste. Both waste have different characters, physically and chemically. Waste of PT ANTAM major contaminant was cianide (Cn whereas people mine waste major contamin