WorldWideScience

Sample records for affecting lipofection potency

  1. Exogenous DNA internalisation by sperm cells is improved by combining lipofection and restriction enzyme mediated integration.

    Science.gov (United States)

    Churchil, R R; Gupta, J; Singh, A; Sharma, D

    2011-06-01

    1. Three types of exogenous DNA inserts, i.e. complete linearised pVIVO2-GFP/LacZ vector (9620 bp), the LacZ gene (5317 bp) and the GFP gene (2152 bp) were used to transfect chicken spermatozoa through simple incubation of sperm cells with insert. 2. PCR assay, Dot Blot hybridisation and Southern hybridisation showed the successful internalisation of exogenous DNA by chicken sperm cells. 3. Lipofection and Restriction Enzyme Mediated Integration (REMI) were used to improve the rate of internalisation of exogenous DNA by sperm cells. 4. Results from dot blot as well as Southern hybridisation were semi-quantified and improved exogenous DNA uptake by sperm cells through lipofection and REMI. Stronger signals were observed from hybridisation of LacZ as well as GFP specific probe with the DNA from lipofected exogenous DNA transfected sperm DNA in comparison with those transfected with nude exogenous DNA.

  2. Single-cell real-time imaging of transgene expression upon lipofection

    Energy Technology Data Exchange (ETDEWEB)

    Fiume, Giuseppe [Center for Nanotechnology Innovation @NEST, Istituto Italiano di Tecnologia, Piazza San Silvestro 12, 56127 Pisa (Italy); Di Rienzo, Carmine [Center for Nanotechnology Innovation @NEST, Istituto Italiano di Tecnologia, Piazza San Silvestro 12, 56127 Pisa (Italy); NEST, Scuola Normale Superiore and Istituto Nanoscienze-CNR, Piazza San Silvestro 12, 56127, Pisa (Italy); Marchetti, Laura [Center for Nanotechnology Innovation @NEST, Istituto Italiano di Tecnologia, Piazza San Silvestro 12, 56127 Pisa (Italy); Pozzi, Daniela; Caracciolo, Giulio [Department of Molecular Medicine, “Sapienza” University of Rome, Viale Regina Elena 291, 00161, Rome (Italy); Cardarelli, Francesco, E-mail: francesco.cardarelli@iit.it [Center for Nanotechnology Innovation @NEST, Istituto Italiano di Tecnologia, Piazza San Silvestro 12, 56127 Pisa (Italy)

    2016-05-20

    Here we address the process of lipofection by quantifying the expression of a genetically-encoded fluorescent reporter at the single-cell level, and in real-time, by confocal imaging in live cells. The Lipofectamine gold-standard formulation is compared to the alternative promising DC-Chol/DOPE formulation. In both cases, we report that only dividing cells are able to produce a detectable amount of the fluorescent reporter protein. Notably, by measuring fluorescence over time in each pair of daughter cells, we find that Lipofectamine-based transfection statistically yields a remarkably higher degree of “symmetry” in protein expression between daughter cells as compared to DC-Chol/DOPE. A model is envisioned in which the degree of symmetry of protein expression is linked to the number of bioavailable DNA copies within the cell before nuclear breakdown. Reported results open new perspectives for the understanding of the lipofection mechanism and define a new experimental platform for the quantitative comparison of transfection reagents. -- Highlights: •The process of lipofection is followed by quantifying the transgene expression in real time. •The Lipofectamine gold-standard is compared to the promising DC-Chol/DOPE formulation. •We report that only dividing cells are able to produce the fluorescent reporter protein. •The degree of symmetry of protein expression in daughter cells is linked to DNA bioavailability. •A new experimental platform for the quantitative comparison of transfection reagents is proposed.

  3. Single-cell real-time imaging of transgene expression upon lipofection

    International Nuclear Information System (INIS)

    Fiume, Giuseppe; Di Rienzo, Carmine; Marchetti, Laura; Pozzi, Daniela; Caracciolo, Giulio; Cardarelli, Francesco

    2016-01-01

    Here we address the process of lipofection by quantifying the expression of a genetically-encoded fluorescent reporter at the single-cell level, and in real-time, by confocal imaging in live cells. The Lipofectamine gold-standard formulation is compared to the alternative promising DC-Chol/DOPE formulation. In both cases, we report that only dividing cells are able to produce a detectable amount of the fluorescent reporter protein. Notably, by measuring fluorescence over time in each pair of daughter cells, we find that Lipofectamine-based transfection statistically yields a remarkably higher degree of “symmetry” in protein expression between daughter cells as compared to DC-Chol/DOPE. A model is envisioned in which the degree of symmetry of protein expression is linked to the number of bioavailable DNA copies within the cell before nuclear breakdown. Reported results open new perspectives for the understanding of the lipofection mechanism and define a new experimental platform for the quantitative comparison of transfection reagents. -- Highlights: •The process of lipofection is followed by quantifying the transgene expression in real time. •The Lipofectamine gold-standard is compared to the promising DC-Chol/DOPE formulation. •We report that only dividing cells are able to produce the fluorescent reporter protein. •The degree of symmetry of protein expression in daughter cells is linked to DNA bioavailability. •A new experimental platform for the quantitative comparison of transfection reagents is proposed.

  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

    to covalent conjugation was compared with regards to the transepithelial permeation. CPP-conjugated PTH(1-34) fusion peptides were successfully expressed in Escherichia coli and purified from inclusion bodies. No clear correlation between the degree of secondary structure of the CPP-conjugated PTH(1......Delivery of therapeutic peptides and proteins by the use of cell-penetrating peptides (CPPs) as carriers has been suggested as a feasible strategy. The aim of the present study was to investigate the effect of conjugating a series of well-known CPPs to the biologically active part of parathyroid...... 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. 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

  6. Lipofection of siRNA into bovine 8-16-cell stage embryos using zona removal and the well-of-the-well culture system.

    Science.gov (United States)

    Ikeda, Shuntaro; Sugimoto, Miki; Kume, Shinichi

    2018-04-13

    Bovine preimplantation embryos exhibit dramatic biological changes between before and after the 8-16-cell stage. Here we report a simple lipofection method to transfect siRNA into bovine 8-16-cell stage embryos using zona removal and the well-of-the-well (WOW) culture system. Bovine one-cell embryos produced in vitro were freed from the zona pellucida and cultured up to the 8-16-cell stage in WOW dishes. The 8-16-cell embryos were lipofected with siRNA and the transfection efficiency was assessed at 48 h of transfection. Lipofection with a red fluorescent non-targeting siRNA revealed the importance of zona removal for transfection of siRNA into embryos. Using this method, we knocked down the methionine adenosyltransferase 2A (MAT2A) gene, achieving a significant reduction in MAT2A expression (P < 0.05) concomitant with the marked inhibition of blastocyst development. Our proposed method, tentatively named 'Octo-lipofection', may be useful to analyze gene functions in bovine preimplantation embryos without expensive equipment and skill-intensive techniques.

  7. 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.

  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. Opioid analgesics: does potency matter?

    Science.gov (United States)

    Passik, Steven D; Webster, Lynn

    2014-01-01

    Prescription opioid analgesics with a wide range of potencies are currently used for the treatment of chronic pain. Yet understanding the clinical relevance and therapeutic consequences of opioid potency remains ill defined. Both patients and clinicians alike have misperceptions about opioid potency, expecting that less-potent opioids will be less effective or fearing that more-potent opioids are more dangerous or more likely to be abused. In this review, common myths about the potency of opioid analgesics will be discussed. Clinicians should understand that pharmacologic potency per se does not necessarily imply more effective analgesia or higher abuse liability. Published dose conversion tables may not accurately calculate the dose for effective and safe rotation from one opioid to another in patients receiving long-term opioid therapy because they are based on limited data that may not apply to chronic pain. Differences in pharmacologic potency are largely accounted for by the actual doses prescribed, according to individualized patient need. Factors for achieving effective analgesia and reducing the risks involved with opioid use include careful medication selection based on patient characteristics, appropriate dosing titration and opioid rotation practices, knowledge of product formulation characteristics (eg, extended release, immediate release, and tamper-resistant features), and an awareness of differences in opioid pharmacokinetics and metabolism. Clinicians should remain vigilant in monitoring patients on any opioid medication, regardless of classification along the opioid potency continuum.

  10. Mediating Potency and Fear

    DEFF Research Database (Denmark)

    Christiansen, Steen Ledet

    2018-01-01

    ’ [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....... Adey, M. Whitehead, and A.J. Williams, eds. From above: war, violence and verticality. London: Hurst & Company]. Through a sensory assault of intense bass soundtracks, kinetic camera movements, and intense CGI effects action movies work to produce what Steven Shaviro has termed ‘intensity effects....... Robin James significantly posits a drone atmosphere where our perceptual limit reconfigures through ‘droning’ – the creation of an affective timbre [James, R., 2013. Drones, sound, and super-panoptic surveillance. Cyborgology]. As James argues, ‘[d]roning rivets you to material conditions, affects...

  11. SHORT COMMUNICATION CARCINOGENIC POTENCY OF ...

    African Journals Online (AJOL)

    SHORT COMMUNICATION. CARCINOGENIC POTENCY OF POLYCYCLIC AROMATIC HYDROCARBONS IN. SOIL. Okoro Dukea* and Ikolo O. Albertb. aDepartment of Chemistry, Delta State University, Abraka, Delta State, Nigeria. bNational Agency for Food and Drug Administration and Control, Central Laboratory, ...

  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. 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.

  14. 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.

  15. 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

    Purpose: Impotence is a familiar sequela of definitive external beam radiation therapy (EBRT) for localized prostate cancer; however, nerve-sparing radical prostatectomy (NSRP) has offered potency rates as high as 70% for selected for patients in several large series. To the authors' knowledge, age and stage-matched comparisons between the effects of EBRT and NSRP upon the normal age trend of impotence have not been performed. Herein, we report the change in potency over time in an EBRT-treated population, determine the significantly predisposing health factors affecting potency in this population, and compare age and stage-matched potency rates with those of normal males and prostatectomy patients. Methods and Materials: Our results are obtained from a retrospective study of 114 patients ranging in age from 52 to 85 (mean, 68) who were diagnosed with clinical stages A-C C (T1-T4N0M0) prostate cancer and then treated conformally with megavoltage x-rays to 6500-7000 cGy (180-200 cGy per fraction) using the four-field box technique. Information concerning pre-RT potency, medical and surgical history, and medications was documented for each patient as was time of post-RT change in potency during regular follow-up. The median follow-up time was 18.5 months. Results: The actuarial probability of potency for all patients gradually decreased throughout post-RT follow-up. At months 1, 12, 24, and 36, potency rates were 98, 92, 75, and 66%, respectively. For those patients who became impotent, the median time to impotence was 14 months. Factors identified from logistic regression analysis as significant predictors of post-EBRT impotence include pre-EBRT partial potency (p < 0.001), vascular disease (p < 0.001), and diabetes (p = 0.003). Next, an actuarial plot of potency probability to patient age for the EBRT-treated population was compared to that obtained from the Massachusetts Male Aging Study of normal males. The two curves were not significantly different (logrank

  16. Assaying the Potency of Influenza Vaccines

    Directory of Open Access Journals (Sweden)

    Philip D. Minor

    2015-02-01

    Full Text Available The potency of vaccines must be determined to ensure that the appropriate dose is given. The manufacture and assessment of influenza vaccines are complicated by the continuously changing nature of the pathogen, which makes efficacy estimates difficult but also confounds attempts to produce a well-validated, consistent potency assay. Single radial diffusion has been used for decades and provides a relatively simple way to measure the amount of biologically active materials present in the vaccine. It requires reagents, which are updated on a regular, frequently yearly, basis and alternative methods continue to be sought.

  17. The Effects of Word Potency, Frequency, and Graphic Characteristics on Word Recognition in the Parafoveal Field.

    Science.gov (United States)

    Gima, Shinye

    A study investigated the theory that the affective dimension of words can have a significant effect on the process of word recognition. Specifically, the study examined whether word potency (the emotional impact of a word), frequency, and certain graphic characteristics affected word recognition in the parafoveal field under very brief exposure…

  18. Anaesthetic potency and physiological effects of refrigerated ...

    African Journals Online (AJOL)

    Several in vitro studies have justified the use of thiopentone solutions beyond the period recommended by the manufacturer. We conducted this in vivo study to investigate the anaesthetic potency and physiological effect of refrigerated thiopentone solution. Rabbits in four groups designated A, B, C and D were ...

  19. 21 CFR 640.56 - Quality control test for potency.

    Science.gov (United States)

    2010-04-01

    ... 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 test for potency. (a) Quality control tests for potency of antihemophilic factor shall be conducted...

  20. Incipient cytotoxicity: A time-independent measure of cytotoxic potency in vitro.

    Science.gov (United States)

    Gülden, Michael; Kähler, Daria; Seibert, Hasso

    2015-09-01

    Time is an important determinant of toxicity but largely ignored in in vitro toxicity assays where exposure times chosen are rather arbitrary. To investigate the impact of time on the cytotoxic potency of chemicals in vitro, the concentration dependent cytotoxic action of selected chemicals (surfactants, metals, oxidative stressors, a mitochondrial poison) was determined after various exposure times (1-72 h) in cultures of Balb/c 3T3 cells. Time affected the cytotoxic potency as well as the cytotoxic efficacy. The median cytotoxic concentrations, EC50, decreased and in most cases approached an "incipient" value, EC50,∞, within 72 h. Cytotoxicity due to mitochondrial insult occurred after a threshold time which was dependent on the medium glucose concentration. Within the chemicals studied the extent of potency change with time ranged from 3- to >1000-fold and the "time to incipient cytotoxicity", tic, from 4 to >72 h. Hence, also the relative cytotoxic potencies depend on exposure time. Ignoring this may lead to severe bias in toxicological hazard and risk assessment. Therefore it is recommended to determine the incipient cytotoxic potency of chemical compounds, represented by, e.g., the incipient median effect (EC50,∞), no effect (NEC∞) or lowest effect concentrations (LEC∞) instead of measures obtained after arbitrary exposure times. If this is not possible, the 72 h-potency measurements appear to be useful surrogates. These time-independent incipient potency values can be reasonably compared between substances, endpoints, cells and biological test systems and may serve to define points of departure for quantitative in vitro-in vivo extrapolations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Clostridium oedematiens: observations on potency assaying.

    Science.gov (United States)

    Macheak, M E

    1976-01-01

    The United States has established a Standard Requirement for the potency testing of biological products containing Clostridium oedematiens belonging to two types: type B (Cl. novyi) and type D (Cl. haemolyticum). Guinea pig testing has provided widely varying results depending on the origin of the animals. The tests reported are intended to determine the efficacity of the vaccines (Cl. novyi and Cl. haemolyticum) depending on the animal tested: guinea pigs, sheep and bovines; they further establish a parallelism between the antitoxin titer and the immunity of the animal.

  2. Differential influence of dopamine transport rate on the potencies of cocaine, amphetamine, and methylphenidate.

    Science.gov (United States)

    Calipari, Erin S; Ferris, Mark J; Siciliano, Cody A; Jones, Sara R

    2015-01-21

    Dopamine transporter (DAT) levels vary across brain regions and individuals, and are altered by drug history and disease states; however, the impact of altered DAT expression on psychostimulant effects in brain has not been systematically explored. Using fast scan cyclic voltammetry, we measured the effects of elevated DAT levels on presynaptic dopamine parameters as well as the uptake inhibition potency of the blockers cocaine and methylphenidate (MPH) and the releaser amphetamine (AMPH) in the nucleus accumbens core. Here we found that increases in DAT levels, resulting from either genetic overexpression or MPH self-administration, caused markedly increased maximal rates of uptake (Vmax) that were positively correlated with the uptake inhibition potency of AMPH and MPH, but not cocaine. AMPH and MPH were particularly sensitive to DAT changes, with a 100% increase in Vmax resulting in a 200% increase in potency. The relationship between Vmax and MPH potency was the same as that for AMPH, but was different from that for cocaine, indicating that MPH more closely resembles a releaser with regard to uptake inhibition. Conversely, the effects of MPH on stimulated dopamine release were similar to those of cocaine, with inverted U-shaped increases in release over a concentration-response curve. This was strikingly different from the release profile of AMPH, which showed only reductions at high concentrations, indicating that MPH is not a pure releaser. These data indicate that although MPH is a DAT blocker, its uptake-inhibitory actions are affected by DAT changes in a similar manner to releasers. Together, these data show that fluctuations in DAT levels alter the potency of releasers and MPH but not blockers and suggest an integral role of the DAT in the addictive potential of AMPH and related compounds.

  3. 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

  4. 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

  5. Effect of high-potency cannabis on corpus callosum microstructure.

    Science.gov (United States)

    Rigucci, S; Marques, T R; Di Forti, M; Taylor, H; Dell'Acqua, F; Mondelli, V; Bonaccorso, S; Simmons, A; David, A S; Girardi, P; Pariante, C M; Murray, R M; Dazzan, P

    2016-03-01

    The use of cannabis with higher Δ9-tetrahydrocannabinol content has been associated with greater risk, and earlier onset, of psychosis. However, the effect of cannabis potency on brain morphology has never been explored. Here, we investigated whether cannabis potency and pattern of use are associated with changes in corpus callosum (CC) microstructural organization, in patients with first-episode psychosis (FEP) and individuals without psychosis, cannabis users and non-users. The CC of 56 FEP (37 cannabis users) and 43 individuals without psychosis (22 cannabis users) was virtually dissected and segmented using diffusion tensor imaging tractography. The diffusion index of fractional anisotropy, mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity was calculated for each segment. Across the whole sample, users of high-potency cannabis had higher total CC MD and higher total CC AD than both low-potency users and those who never used (p = 0.005 and p = 0.004, respectively). Daily users also had higher total CC MD and higher total CC AD than both occasional users and those who never used (p = 0.001 and p cannabis is associated with disturbed callosal microstructural organization in individuals with and without psychosis. Since high-potency preparations are now replacing traditional herbal drugs in many European countries, raising awareness about the risks of high-potency cannabis is crucial.

  6. Solvatochromic dyes detect the presence of homeopathic potencies.

    Science.gov (United States)

    Cartwright, Steven J

    2016-02-01

    A systematic approach to the design of simple, chemical systems for investigating the nature of homeopathic medicines has led to the development of an experimental protocol in which solvatochromic dyes are used as molecular probes of serially diluted and agitated solutions. Electronic spectroscopy has been used to follow changes in the absorbance of this class of dyes across the visible spectrum in the presence of homeopathic potencies. Evidence is presented using six different solvatochromic dyes in three different solvent systems. In all cases homeopathic potencies produce consistent and reproducible changes in the spectra of the dyes. Results suggest that potencies influence the supramolecular chemistry of solvatochromic dyes, enhancing either dye aggregation or disaggregation, depending upon dye structure. Comparable dyes lacking the intramolecular charge transfer feature of solvatochromic dyes are unaffected by homeopathic potencies, suggesting potencies require the oscillating dipole of solvatochromic dyes for effective interaction. The implications of the results presented, both for an eventual understanding of the nature of homeopathic medicines and their mode of action, together with future directions for research in this area, are discussed. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

  7. Developing of Environmental Education Textbook Based on Local Potencies

    Science.gov (United States)

    Ilma, Silfia; Wijarini, Fitri

    2017-01-01

    Environmental education subject aims to form students who have the character to maintain the environment. One effort to achieve the objectives of the Environmental education subject is the local Environmental Education Textbook Based on Local Potencies. This research was aimed to produce textbook of environment-based education subject…

  8. Comparative Study on The Potency of Antibiotic Discs With ...

    African Journals Online (AJOL)

    Our results showed that antibiotics disc was more effective than the commercially sold antibiotics and that both organisms were resistant to Ampicillin but susceptible to Gentamicin and. Ciprofloxacin. Keywords: Potency, Antibiotics, Disc Isolates, Urinary tract. INTRODUCTION. The urinary system is structured in a way that.

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

    African Journals Online (AJOL)

    Marking (1967) and Houston & Woods (1976) also showed that the anaesthetic potency of a drug depends on the temperature of the water at which anaesthesia is in- duced. The results of this study confmn these fmdings because the induction of anaesthesia at different water temperatures resulted in different anaesthetic ...

  10. Are High Potency Multivitamin Syrups Toxic | Mendle | Nigerian ...

    African Journals Online (AJOL)

    Background: High potency liquid multivitamin preparations contain many active vitamin ingredients having maximal daily dosage and formulated for prolonged administrations. They are intended to be used as food supplements and in the treatment or prophylaxis of vitamin deficiencies. Multivitamin preparations are highly ...

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

    African Journals Online (AJOL)

    Three fibrolytic bacteria were isolated from sheep's colon using cellulose (b), xylan (c) and lignin (d) as selective substrates. The potency of fibrolytic was identified by Subbarao methods. These isolates were then used both in pure and mixed culture with cattle cellulolytic bacteria (a) from the previous research. The isolates ...

  12. 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 ...

  13. Potency of aqueous stem bark extract of Khaya senegalensis ...

    African Journals Online (AJOL)

    In order to assess the potency of aqueous stem bark extract of Khaya senegalensis (KS) against liver diseases, serum aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were assayed in rats treated with two (2) different doses of the extract after the induction of liver damage in the ...

  14. A laboratory assessment of the potential molluscicidal potency of ...

    African Journals Online (AJOL)

    Preliminary laboratory studies were conducted to determine the molluscicidal potency of Jatropha curcas, the physic nut. Biomphalaria glabrata and Bulinus globosus snails were exposed to varying concentrations of aqueous extracts of crushed J. curcas seeds from unripe, ripe and overripe fruits collected from two ...

  15. Relative potency of ethanol extracts of stem bark of Sacoglottis ...

    African Journals Online (AJOL)

    Larvae in the controls were agile throughout the duration of experiment. Thus stem bark of S. gabonensis and seed of P.nitida are potential agents for the control of An. gambiae which is one of the vectors of malaria and filariasis. Key Words: Relative potency, Sacoglottis gabonensis, Picralima nitida, Anopheles gambiae ...

  16. 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 ...

  17. Comparison Of The Safety, Immunogeni City And Potency Of La ...

    African Journals Online (AJOL)

    Some Poultry vaccines found in Nigeria are imported. Therefore, there is a need to compare the safety, immunogenicity and potency of some of the vaccines used to control Newcastle disease (ND) particularly La Sota ND vaccines and the V4 ND vaccine. A total of 120 day — o Id pullets were obtained from a commercial ...

  18. carcinogenic potency of polycyclic aromatic hydrocarbons in soil

    African Journals Online (AJOL)

    Carcinogenic potency of polycyclic aromatic hydrocarbons (PAHs) in soils obtained from seven different sampling locations in Effurun metropolis and its environs of Niger Delta Area of Nigeria were evaluated. The 16 US EPA priority PAHs were determined with GC-MS. The concentrations of individual PAHs observed were ...

  19. Polycyclic Aromatic Hydrocarbons in Air and their Toxic Potency

    Indian Academy of Sciences (India)

    GENERAL I ARTICLE. Polycyclic Aromatic Hydrocarbons in Air and their Toxic Potency. R Mohanraj is currently working as Senior Research. Fellow in Environmental. Impact Assessment (EIA). Division of Salim Ali Centre for Ornithology and Natural. History (SACON),. Coimbatore. His primary interest lies in aerosol.

  20. 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 ...

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

    African Journals Online (AJOL)

    The anaesthetic potency of benzocaine-hydrochloride in three freshwater fish species. J.T. Ferreira, H.J. Schoonbee and G.L. Smit. Research Unit for Fish Biology, Rand Afrikaans University, Johannesburg. Anaesthesia was induced in the common carp, Cyprinus carpio, tilapia, Oreochromis mossambicus and rainbow trout, ...

  2. 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.

  3. 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.

  4. 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...

  5. 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.

  6. 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...

  7. 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.

  8. Epoxy resin monomers with reduced skin sensitizing potency.

    Science.gov (United States)

    O'Boyle, Niamh M; Niklasson, Ida B; Tehrani-Bagha, Ali R; Delaine, Tamara; Holmberg, Krister; Luthman, Kristina; Karlberg, Ann-Therese

    2014-06-16

    Epoxy resin monomers (ERMs), especially diglycidyl ethers of bisphenol A and F (DGEBA and DGEBF), are extensively used as building blocks for thermosetting polymers. However, they are known to commonly cause skin allergy. This research describes a number of alternative ERMs, designed with the aim of reducing the skin sensitizing potency while maintaining the ability to form thermosetting polymers. The compounds were designed, synthesized, and assessed for sensitizing potency using the in vivo murine local lymph node assay (LLNA). All six epoxy resin monomers had decreased sensitizing potencies compared to those of DGEBA and DGEBF. With respect to the LLNA EC3 value, the best of the alternative monomers had a value approximately 2.5 times higher than those of DGEBA and DGEBF. The diepoxides were reacted with triethylenetetramine, and the polymers formed were tested for technical applicability using thermogravimetric analysis and differential scanning calorimetry. Four out of the six alternative ERMs gave polymers with a thermal stability comparable to that obtained with DGEBA and DGEBF. The use of improved epoxy resin monomers with less skin sensitizing effects is a direct way to tackle the problem of contact allergy to epoxy resin systems, particularly in occupational settings, resulting in a reduction in the incidence of allergic contact dermatitis.

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

    Science.gov (United States)

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

    2017-10-10

    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. 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.

  11. 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.

  12. 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.

  13. Geohydrology, geochemistry, geothermal potency of Rianiate Toba Lake North Sumatera

    Science.gov (United States)

    Nainggolan, Juliper; Sitepu, Cristin; Pardede, Sanggam; Diantoro, Markus

    2017-09-01

    This research was performed to determine the potency of Rianiate’s geothermal an alternative of energy source and determine the types of geothermal that was begun with the position’s measurement by using GPS (Global Position System), and then the direct observation of chemical and physical properties such as pH, surface’s temperature, color etc. The following steps were taking sample in four different springs indicated by spring 1, spring 2, spring 3, and spring 4. The chemical nature was measured by titrimetry method by using AAS, XRD, and gas Chromathology. The calculating of temperature of subsurface has done by using geothermometer and sequentially followed by geothermal potency’s calculation. The position of four springs are located about N: 02° 31,852’ and E: 098° 44. 021’ where were average height from sea’s level is 958 m. The highest surface’s temperature is 80 °C and the temperature under soil is about 130.5 °C described the average of geothermal. The calculation of content of chloride, sulfate, bicarbonations revealed that the water can be categorized as chloride type. The trilateral diagram Na/1000 - K/100 - √Mg of hot water is in the regime of immature water. From the calculation of Indonesia’s Standardized Geotherm, it was obtained that the estimated reservoir potency of Rianiate geotherm is 2,68 MWe.

  14. The Potency of Halim Perdanakusuma Airport Development as Commercial Airport

    Directory of Open Access Journals (Sweden)

    Miming Miharja

    2017-04-01

    Full Text Available Nowadays, Halim Perdanakusuma Airport plays a role in facilitating commercial and military flight activities. In the commercial flight segment, the role of Halim Perdanakusuma airport is expected to reduce the load of Soekarno-Hatta International Airport in serving the ever increasing flight volume. As part of this concern, this article analyzes the potency of Halim Perdanakusuma Aiport to respond the growing demand of commercial flight based on land side and air side development potential factors. The potency of development from land side is based on the space availability to meet the standard of passenger service facilities, whereas the air side is based on the airport runway capacity in accommodating the number of aircraft take-off and landing activities according to their types as well as loading capacities. The need for airport development is based on the standard of space needs for each passenger during the peak time. Analysis result shows that the most critical constraint is coming from land sidedue to space limitation for the development of various facilities required to fulfil the service standard, which available only for up to 2,750,369 total passengers per year. Meanwhile, there is no significant constraint for airport development from the air side point of view.

  15. 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.

  16. Serum Concentration of Nine Hormones in Aging Male Population and Association with Potency and Libido Problems

    OpenAIRE

    Galić, Josip; Šimunović, Dalibor

    2006-01-01

    Aim was to determine if a serum levels of free testosterone and selected eight hormones are in correlation with potency and libido problems in aging male. Male population older then 45 years of two Slavonian villages was called for voluntary examination. Every patient filled a questionnaire concerning medical history, operations and potency and libido problems. Based on answers we formed six groups of patients, but only three were analyzed further. Population with potency and libi...

  17. 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

  18. A comparison of potency differences among thyroid peroxidase (TPO) inhibitors to induce developmental toxicity and other thyroid gland-linked toxicities in humans and rats.

    Science.gov (United States)

    Motonaga, Kozo; Ota, Mika; Odawara, Kyoko; Saito, Shoji; Welsch, Frank

    2016-10-01

    The potencies of resorcinol, 6-propylthiouracil (PTU) and methimazole (MMI) for inducing developmental toxicity and neurotoxicity were compared in pregnant rats, regarded as valid model for human thyroid toxicity. Profound differences on maternal thyroid hormone levels (THs), maternal toxicity as well as developmental and neurotoxicity sequelae occurred. Resorcinol affected none of those end points. PTU and MMI caused significant effects. Therapy with either PTU or MMI during the first trimester of human pregnancy can cause reductions of maternal THs, accompanied by disruptions of prenatal development. Clinical MMI studies show sporadic evidence of teratogenic effects, with equivocal relation to thyroid peroxidase (TPO) inhibition. In recent decades no MMI associated prenatal toxicity has been reported, an outcome possibly related to carefully managed therapy. Orally administered resorcinol was rapidly absorbed, metabolized and excreted and was undetectable in the thyroid. In contrast, PTU or MMI accumulated. Resorcinol's potency to inhibit TPO was profoundly lower than that of PTU or MMI. Quantum chemical calculations may explain low resorcinol reactivity with TPO. Thus, distinctions in the target organ and the TPO inhibitory potency between these chemicals are likely contributing to different reductions of maternal THs levels and affecting the potency to cause developmental toxicity and neurotoxicity. Copyright © 2016. Published by Elsevier Inc.

  19. Iloprost, Prostaglandin E1, and Papaverine Relax Human Mesenteric Arteries With Similar Potency.

    Science.gov (United States)

    Mahlke, Christoph; Kühn, Jens-Peter; Mensel, Birger; Schreiber, André; Juretzko, Annett; Steinbach, Antje; Grisk, Olaf

    2017-09-01

    Nonocclusive mesenteric ischemia (NOMI) is accompanied by mesenteric artery spasms that are at least in part due to endothelin system activation. Acute treatment includes intra-arterial infusion of vasodilators such as iloprost, prostaglandin E1 (PGE1), and papaverine. Their effectiveness is not well characterized in human mesenteric arteries. We directly compared their potency to relax isolated human mesenteric arteries. To explore the potential of Rock inhibition to treat mesenteric artery spasms, we tested if endothelin-1 (ET-1)-induced mesenteric artery constrictions depend on rho kinase (Rock). Mesenteric artery segments were obtained from patients who underwent elective abdominal surgery. Vasodilator concentration-response curves were recorded from ET-1-preconstricted vessels by small vessel myography. Rock expression was investigated by Western blot and the potency of Rock inhibition to blunt ET-1-induced mesenteric artery constriction was tested. Iloprost, PGE1, and papaverine similarly reduced vascular tone to 20% to 30% of ET-1-induced wall tension. In human mesenteric arteries, logEC50 was significantly less for iloprost than for PGE1 or papaverine. Respective logEC50 values were -7.72 ± 0.08 mol/L, -6.58 ± 0.17 mol/L, and -6.73 ± 0.19 mol/L in 150 μm to 300 μm lumen diameter arteries. These vessels were also more sensitive to iloprost than 500 μm to 1,000 μm lumen diameter arteries (logEC50 -7.29 ± 0.07 mol/L). Rock1 and Rock2 were expressed in human mesenteric arteries but Rock inhibition did not significantly affect ET-1-induced vasoconstrictions. Iloprost, PGE1, and papaverine have a similar potency to relax mesenteric arteries. Our data suggest that iloprost but not Rock inhibition may be particularly useful to treat ET-1-induced spasms of distal mesenteric arteries.

  20. Replacing antibodies with modified DNA aptamers in vaccine potency assays.

    Science.gov (United States)

    Trausch, Jeremiah J; Shank-Retzlaff, Mary; Verch, Thorsten

    2017-10-04

    Vaccine in vitro potency assays are vital regulatory tests that are used to confirm the presence and concentration of an antigen of interest in a form that directly or indirectly relates to protective activity in patients. Current assays come in many forms, but they almost exclusively use antibody reagents for selective detection of the target antigen. Antibodies provide specific recognition of vaccine antigens but also exhibit drawbacks such as stability limitations, cost, and lot-to-lot variation, which can make it challenging to maintain the reagent throughout the lifetime of the vaccine. We explored replacing antibodies with aptamers. Aptamers are macromolecules, such as nucleic acids, which can bind to their targets with high specificity and affinity, similar to that of antibodies. Some of the advantages of using aptamers over antibodies is that aptamers can be more stable, smaller, less expensive to produce, synthesized in vitro, and logistically easier to supply throughout the multi-decade lifespan of a commercial vaccine. We created modified DNA aptamers against the common vaccine carrier protein, CRM 197 . Several aptamers were discovered and one was chosen for further characterization. The binding kinetics of the aptamer revealed an off-rate 16-fold slower than anti-CRM 197 antibodies used for comparison. The aptamers were more sensitive than available antibodies in some assay formats and comparable in others. The aptamer epitope was mapped to the receptor-binding domain of CRM 197 , a site adjacent to a known antibody binding site. These data address some key aspects for a path forward in replacing antibodies with aptamers for use as critical reagents in vaccine assays. We further highlight the possibility of using nucleic acid reagents to develop next generation potency assays. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Glycogen-gold nanohybrid escalates the potency of silymarin.

    Science.gov (United States)

    Kandimalla, Raghuram; Dash, Suvakanta; Bhowal, Ashim Chandra; Kalita, Sanjeeb; Talukdar, Narayan Chandra; Kundu, Sarathi; Kotoky, Jibon

    2017-01-01

    In this study, a glycogen-gold nanohybrid was fabricated to enhance the potency of a promising hepatoprotective agent silymarin (Sly) by improving its solubility and gut permeation. By utilizing a facile green chemistry approach, biogenic gold nanoparticles were synthesized from Annona reticulata leaf phytoconstituents in combination with Sly (SGNPs). Further, the SGNPs were aggregated in glycogen biopolymer to yield the therapeutic nanohybrids (GSGNPs). Transmission electron microscopy, UV-Vis spectroscopy, X-ray diffraction, and Fourier transform infrared spectroscopy analysis confirmed the successful formation and conjugation of both SGNPs and GSGNPs. The fabricated nanohybrids showed significant protection against CCl 4 -induced hepatic injury in Wistar rats and maintained natural antioxidant (superoxide dismutase and catalase) levels. Animals treated with GSGNPs (10 mg/kg) and SGNPs (20 mg/kg) retained usual hepatic functions with routine levels of hepatobiliary enzymes (aspartate transferase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase) and inflammatory markers (interleukin-1β and tumor necrosis factor-α) with minimal lipid peroxidation, whereas those treated with 100 mg/kg of Sly showed the similar effect. These results were also supported by histopathology of the livers where pronounced hepatoprotection with normal hepatic physiology and negligible inflammatory infiltrate were observed. Significant higher plasma C max supported the enhanced bioavailability of Sly upon GSGNPs treatment compared to SGNPs and free Sly. Graphite furnace atomic absorption spectrophotometry analysis also substantiated the efficient delivery of GSGNPs over SGNPs. The fabricated therapeutic nanohybrids were also found to be biocompatible toward human erythrocytes and L929 mouse fibroblast cells. Overall, due to increased solubility, bioavailability and profuse gut absorption; GSGNPs demonstrated tenfold enhanced potency compared to free Sly.

  2. Glycogen–gold nanohybrid escalates the potency of silymarin

    Science.gov (United States)

    Kandimalla, Raghuram; Dash, Suvakanta; Bhowal, Ashim Chandra; Kalita, Sanjeeb; Talukdar, Narayan Chandra; Kundu, Sarathi; Kotoky, Jibon

    2017-01-01

    In this study, a glycogen–gold nanohybrid was fabricated to enhance the potency of a promising hepatoprotective agent silymarin (Sly) by improving its solubility and gut permeation. By utilizing a facile green chemistry approach, biogenic gold nanoparticles were synthesized from Annona reticulata leaf phytoconstituents in combination with Sly (SGNPs). Further, the SGNPs were aggregated in glycogen biopolymer to yield the therapeutic nanohybrids (GSGNPs). Transmission electron microscopy, UV–Vis spectroscopy, X-ray diffraction, and Fourier transform infrared spectroscopy analysis confirmed the successful formation and conjugation of both SGNPs and GSGNPs. The fabricated nanohybrids showed significant protection against CCl4-induced hepatic injury in Wistar rats and maintained natural antioxidant (superoxide dismutase and catalase) levels. Animals treated with GSGNPs (10 mg/kg) and SGNPs (20 mg/kg) retained usual hepatic functions with routine levels of hepatobiliary enzymes (aspartate transferase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase) and inflammatory markers (interleukin-1β and tumor necrosis factor-α) with minimal lipid peroxidation, whereas those treated with 100 mg/kg of Sly showed the similar effect. These results were also supported by histopathology of the livers where pronounced hepatoprotection with normal hepatic physiology and negligible inflammatory infiltrate were observed. Significant higher plasma Cmax supported the enhanced bioavailability of Sly upon GSGNPs treatment compared to SGNPs and free Sly. Graphite furnace atomic absorption spectrophotometry analysis also substantiated the efficient delivery of GSGNPs over SGNPs. The fabricated therapeutic nanohybrids were also found to be biocompatible toward human erythrocytes and L929 mouse fibroblast cells. Overall, due to increased solubility, bioavailability and profuse gut absorption; GSGNPs demonstrated tenfold enhanced potency compared to free Sly. PMID

  3. Potency of Mahakam Delta in East Kalimantan, Indonesia

    Directory of Open Access Journals (Sweden)

    Zairin Zain

    2014-04-01

    Full Text Available Normal 0 false false false IN X-NONE X-NONE Mahakam Delta is not only utilized for fishery activities but also for several industrial purposes such as coal and oil mining, shipping and timber. The objective of this paper is to provide information in term of the potency of Mahakam Delta located in East Kalimantan province, Indonesia. The study was conducted in Mahakam Delta, East Kalimantan Province, Indonesia. Participatory rural appraisal is a group of methods to collect information in a participatory fashion from rural communities. The method employed in this research was descriptive analysis describing the environmental potency found in Mahakam Delta. Massive conversion of mangrove forest particularly Nypa (Nypa fruticans area into pond has driven conflict among related stakeholders on the utilization of natural resource and land which subsequently impacts on the fish and shrimp source regeneration, loss of ecological functions of mangrove forest for feeding, nursery and spawning ground of fish and other organisms. Besides of fisheries, oil and gas activity also exists in Mahakam Delta. Mahakam Delta is regarded as important area due to the largest producer of oil and gas mining. Thus, oil and gas industry is the most reliable sector that contributes to the economic development of Kutai Kartanegara district. As a resource provider, Mahakam Delta ecosystem provides various resources for livelihoods. As a life-support service provider, Mahakam Delta ecosystem provides habitat and ideal environment to support variety of living kinds. As a convenience provider, Mahakam Delta ecosystem provides unique and interesting recreation site. As a protector from natural disaster, Mahakam Delta ecosystem is able to protect human kinds from natural disaster threatening coastal area.

  4. 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

    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...... of EDCs was reduced in the STPs but not eliminated, as verified by the applied bioassays that all responded to the extracts of effluent samples. Our data suggest that the wastewater treatment processes are not efficient enough to prevent contamination of environmental surface waters. © 2010 SETAC....

  5. 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.

  6. 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.

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

    African Journals Online (AJOL)

    PRECIOUS

    2009-11-16

    Nov 16, 2009 ... The potency of vaccines was tested using the Karber's Formula. Key words: Oral polio vaccine, rhabdomyosarcoma, thermostability, potency. INTRODUCTION. Poliomyelitis, often called polio or infantile paralysis, is an acute viral infectious disease spread from person to person, primarily via the faecal-oral ...

  8. 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...

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

    DEFF Research Database (Denmark)

    Allermann, L; Pejtersen, J; Gunnarsen, L

    2007-01-01

    symptoms correlated with the potency of surface dust. The PD was not related to single building factors. The inflammatory PD may be used as an integrated proxy measure of biologically active compounds in dust, reflecting health relevant properties of the dust. PRACTICAL IMPLICATIONS: The potency of surface...

  10. Serum concentration of nine hormones in aging male population and association with potency and libido problems.

    Science.gov (United States)

    Galić, Josip; Simunović, Dalibor

    2006-12-01

    Aim was to determine if a serum levels of free testosterone and selected eight hormones are in correlation with potency and libido problems in aging male. Male population older then 45 years of two Slavonian villages was called for voluntary examination. Every patient filled a questionnaire concerning medical history, operations and potency and libido problems. Based on answers we formed six groups of patients, but only three were analyzed further. Population with potency and libido problems is on average older. In group of patients with normal potency and libido (PNLN group) average levels of free testosterone are 46.01 pmol/L, LH 4.62 IU/L and FSH 6.20 IU/L. In group of patients with mild-damaged potency and normal libido (PMLN group) average levels of free testosterone are 44.61 pmol/L, LH 6.19 IU/L and FSH 8.18 IU/L. In PALA group of patients with absent potency and libido (PALA group) average levels of free testosterone are 41,89 pmol/L, LH 8.07 IU/L and FSH 11.27 IU/L. Significant higher levels of FSH and LH were found compared with the control group (for FSH plibido and potency problems, this difference is not significant and testosterone deficiency itself can not explain potency and libido problems in aging male.

  11. 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

  12. 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

  13. 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.

  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. Potency of Fish Collagen as a Scaffold for Regenerative Medicine

    Directory of Open Access Journals (Sweden)

    Shizuka Yamada

    2014-01-01

    Full Text Available Cells, growth factors, and scaffold are the crucial factors for tissue engineering. Recently, scaffolds consisting of natural polymers, such as collagen and gelatin, bioabsorbable synthetic polymers, such as polylactic acid and polyglycolic acid, and inorganic materials, such as hydroxyapatite, as well as composite materials have been rapidly developed. In particular, collagen is the most promising material for tissue engineering due to its biocompatibility and biodegradability. Collagen contains specific cell adhesion domains, including the arginine-glycine-aspartic acid (RGD motif. After the integrin receptor on the cell surface binds to the RGD motif on the collagen molecule, cell adhesion is actively induced. This interaction contributes to the promotion of cell growth and differentiation and the regulation of various cell functions. However, it is difficult to use a pure collagen scaffold as a tissue engineering material due to its low mechanical strength. In order to make up for this disadvantage, collagen scaffolds are often modified using a cross-linker, such as gamma irradiation and carbodiimide. Taking into account the possibility of zoonosis, a variety of recent reports have been documented using fish collagen scaffolds. We herein review the potency of fish collagen scaffolds as well as associated problems to be addressed for use in regenerative medicine.

  16. Potency of Fish Collagen as a Scaffold for Regenerative Medicine

    Science.gov (United States)

    Yamamoto, Kohei; Yanagiguchi, Kajiro

    2014-01-01

    Cells, growth factors, and scaffold are the crucial factors for tissue engineering. Recently, scaffolds consisting of natural polymers, such as collagen and gelatin, bioabsorbable synthetic polymers, such as polylactic acid and polyglycolic acid, and inorganic materials, such as hydroxyapatite, as well as composite materials have been rapidly developed. In particular, collagen is the most promising material for tissue engineering due to its biocompatibility and biodegradability. Collagen contains specific cell adhesion domains, including the arginine-glycine-aspartic acid (RGD) motif. After the integrin receptor on the cell surface binds to the RGD motif on the collagen molecule, cell adhesion is actively induced. This interaction contributes to the promotion of cell growth and differentiation and the regulation of various cell functions. However, it is difficult to use a pure collagen scaffold as a tissue engineering material due to its low mechanical strength. In order to make up for this disadvantage, collagen scaffolds are often modified using a cross-linker, such as gamma irradiation and carbodiimide. Taking into account the possibility of zoonosis, a variety of recent reports have been documented using fish collagen scaffolds. We herein review the potency of fish collagen scaffolds as well as associated problems to be addressed for use in regenerative medicine. PMID:24982861

  17. RELATIVE POTENCY OF FUNGAL EXTRACTS IN INDUCING ALLERGIC ASTHMA-LIKE RESPONSES IN BALB/C MICE

    Science.gov (United States)

    Indoor mold has been associated with the development of allergic asthma. However, relative potency of molds in the induction of allergic asthma is not clear. In this study, we tested the relative potency of fungal extracts (Metarizium anisophilae [MACA], Stachybotrys ...

  18. 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.

  19. Osteogenic Potency of Nacre on Human Mesenchymal Stem Cells

    Science.gov (United States)

    Green, David W.; Kwon, Hyuk-Jae; Jung, Han-Sung

    2015-01-01

    Nacre seashell is a natural osteoinductive biomaterial with strong effects on osteoprogenitors, osteoblasts, and osteoclasts during bone tissue formation and morphogenesis. Although nacre has shown, in one study, to induce bridging of new bone across large non-union bone defects in 8 individual human patients, there have been no succeeding human surgical studies to confirm this outstanding potency. But the molecular mechanisms associated with nacre osteoinduction and the influence on bone marrow-derived mesenchymal stem cells (BMSC’s), skeletal stem cells or bone marrow stromal cells remain elusive. In this study we highlight the phenotypic and biochemical effects of Pinctada maxima nacre chips and the global nacre soluble protein matrix (SPM) on primary human bone marrow-derived stromal cells (hBMSCs) in vitro. In static co-culture with nacre chips, the hBMSCs secreted Alkaline phosphatase (ALP) at levels that exceeded bone morphogenetic protein (rhBMP-2) treatment. Concentrated preparation of SPM applied to Stro-1 selected hBMSC’s led to rapid ALP secretions, at concentrations exceeding the untreated controls even in osteogenic conditions. Within 21 days the same population of Stro-1 selected hBMSCs proliferated and secreted collagens I–IV, indicating the premature onset of an osteoblast phenotype. The same SPM was found to promote unselected hBMSC differentiation with osteocalcin detected at 7 days, and proliferation increased at 7 days in a dose-dependent manner. In conclusion, nacre particles and nacre SPM induced the early stages of human bone cell differentiation, indicating that they may be promising soluble factors with osteoinductive capacity in primary human bone cell progenitors such as, hBMSC’s. PMID:25666352

  20. 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.

  1. [On the efficacy of a spleenic dialysate (M 40,412) in disturbed potency (author's transl)].

    Science.gov (United States)

    Jovanović, U J

    1976-01-01

    By means of a combined phallographic-exploratory method and using statistical classification we were able to confirm clinically the potency enhancing action of a spleenic dialysate (M 40,412, Solcosplen). The remarkable alleviation of chronic and acute disturbances of potency can be explained not only by the elevated serum testosterone levels but likewise by biochemical mechanisms of action in the target organ, as was demonstrated by a research group. The treatment of potency disorders of different genetical origins yielded as the outstanding conclusions: 1. The interdependence of dream- and erection phases, usually injured in disturbed potency, could be restored by M 40,412. 2. The effect of 40,412 was the more striking the more pronounced were the initial values. 3. A particular type of experiencing (feeling of inferiority and disturbed contact) appears to respond prevailingly well to M 40,412. Further clinical studies are suggested.

  2. 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.

  3. Comparison of Leg Regeneration Potency Between Holometabolous Helicoverpa armigera (Lepidoptera: Noctuidae) and Hemimetabolous Locusta migratoria manilensis (Orthoptera: Acrididae).

    Science.gov (United States)

    Yang, Qingpo; Li, Zhen; Li, Hui; Li, Yanrong; Yang, Yuhui; Zhang, Qingwen; Liu, Xiaoxia

    2016-12-01

    After injury many insects could regenerate lost limb. In this study, Helicoverpa armigera Hubner and Locusta migratoria manilensis (Meyen, 1835) were chosen to compare the regeneration potency of holometabolous and hemimetabolous insects. We employed the classical approach of surgical excision to verify the regeneration ability and to investigate the factors that affect the extent of regeneration. The results found that H. armigera could regenerate intact legs when the larval legs were excised at the first and second instar and that legs of adult H. armigera had a close relationship with their larval counterparts. However, the adult legs became malformed or disappeared when excised at other older instars. For the L. migratoria, we found the legs have weak partial regeneration ability when amputation was conducted at the joint of two segments. The regeneration potency might be stronger the more proximal the operation. Regeneration process had a negative impact on the larval development. This is the first report of complete leg regeneration capacity having a strong correlation with the instar but not with the position where amputation occurred for H. armigera, while for the L. migratoria, partial regenerative ability had a close relationship with the position where amputation occurred but not with instars. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. 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 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.

  5. Parameterizing Dose-Response Models to Estimate Relative Potency Functions Directly

    Science.gov (United States)

    Dinse, Gregg E.

    2012-01-01

    Many comparative analyses of toxicity assume that the potency of a test chemical relative to a reference chemical is constant, but employing such a restrictive assumption uncritically may generate misleading conclusions. Recent efforts to characterize non-constant relative potency rely on relative potency functions and estimate them secondarily after fitting dose-response models for the test and reference chemicals. We study an alternative approach of specifying a relative potency model a priori and estimating it directly using the dose-response data from both chemicals. We consider a power function in dose as a relative potency model and find that it keeps the two chemicals’ dose-response functions within the same family of models for families typically used in toxicology. When differences in the response limits for the test and reference chemicals are attributable to the chemicals themselves, the older two-stage approach is the more convenient. When differences in response limits are attributable to other features of the experimental protocol or when response limits do not differ, the direct approach is straightforward to apply with nonlinear regression methods and simplifies calculation of simultaneous confidence bands. We illustrate the proposed approach using Hill models with dose-response data from U.S. National Toxicology Program bioassays. Though not universally applicable, this method of estimating relative potency functions directly can be profitably applied to a broad family of dose-response models commonly used in toxicology. PMID:22700543

  6. Identification of sequence features that predict competition potency of siRNAs.

    Science.gov (United States)

    Li, Xin; Yoo, Jae Wook; Lee, June Hyung; Hahn, Yoonsoo; Kim, Soyoun; Lee, Dong-Ki

    2010-07-16

    Small interfering RNAs (siRNAs) specifically knock-down target mRNAs via RNA interference (RNAi) mechanism. During this process, introduction of excess amount of exogenous siRNAs could lead to the saturation of cellular RNAi machinery. One consequence of RNAi machinery saturation is the competition between two simultaneously introduced siRNAs, during which one siRNA loses gene silencing activity. Although competition phenomena have been well characterized, the molecular and sequence features of siRNAs that specify the competition potency remain poorly understood. Here, for the first time, we performed a large-scale siRNA competition potency analysis by measuring the competition potency of 56 different siRNAs and ranking them based on their competition potency. We have also established an algorithm to predict the competition potency of siRNAs based upon the conserved sequence features of strong and weak competitor siRNAs. The present study supports our hypothesis that the competition potency of siRNAs is specified by the 5'-half antisense sequence and provides a useful guideline to design siRNAs with minimal RNAi machinery saturation. Copyright 2010 Elsevier Inc. All rights reserved.

  7. 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

  8. 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

  9. Synthetic peptides for in vitro evaluation of the neutralizing potency of Loxosceles antivenoms.

    Science.gov (United States)

    Ramada, Juliani Salvini; Becker-Finco, Alessandra; Minozzo, João Carlos; Felicori, Liza Figueiredo; Machado de Avila, Ricardo Andrez; Molina, Franck; Nguyen, Christophe; de Moura, Juliana; Chávez-Olórtegui, Carlos; Alvarenga, Larissa Magalhães

    2013-10-01

    An important step in the development of therapeutic antivenoms is the pre-clinical testing using in vivo methods to assess their neutralizing potency. For spider antivenoms (Loxosceles species), horse serum potency against the necrotizing activities of Loxosceles intermedia crude venom is currently tested in rabbits. These procedures are time consuming and involve a large number of animals. The aim of this study was to develop an in vitro method to assess the neutralizing potency of anti-Loxosceles sera. We first demonstrated that it was not possible to establish a correlation between the ELISA antibody reactivity of horse anti-Loxosceles serum and their neutralizing potency. We then showed that the antivenoms recognized several peptide epitopes from different regions of SMase-D proteins, which are toxic antigens from Loxosceles venoms. The recognition of some peptides was observed only when high neutralizing potency sera was used. Based on these results, three peptides (peptide 1, DNRRPIWNLAHMVNA and peptide 3, DFSGPYLPSLPTLDA corresponding to residues 2-16 and 164-178, respectively, of SMase-1 protein from Loxosceles laeta, and peptide 2, EFVNLGANSIETDVS corresponding to residues 22-36 of A1H - LoxGa protein from Loxosceles gaucho and LiD1 protein from L. intermedia) were selected. The peptides were synthesized, coupled to bovine serum albumin (BSA), and used as antigens in indirect ELISA to test their reactivity with horse anti-Loxosceles serum of varying neutralizing potencies. We found certain assay conditions that discriminated between the high and low neutralizing potency sera. This study introduced an in vitro and peptide-based neutralization assay for anti-Loxosceles antivenoms. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. van der Waals interactions govern C-β-d-glucopyranosyl triazoles' nM inhibitory potency in human liver glycogen phosphorylase.

    Science.gov (United States)

    Kantsadi, Anastassia L; Stravodimos, George A; Kyriakis, Efthimios; Chatzileontiadou, Demetra S M; Solovou, Theodora G A; Kun, Sándor; Bokor, Éva; Somsák, László; Leonidas, Demetres D

    2017-07-01

    3-(C-Glucopyranosyl)-5aryl-1,2,4-triazoles with an aryl moiety larger than phenyl have been shown to have strong inhibitory potency (K i values in the range of upper nM) for human liver glycogen phosphorylase (hlGP), a pharmacologically relevant target for diabetes type 2. In this study we investigate in a comparative manner the inhibitory effect of the above triazoles and their respective imidazoles on hlGPa. Kinetic studies show that the imidazole derivatives are 6-8 times more potent than their corresponding triazoles. We also seek to answer how the type of the aryl moiety affects the potency in hlGPa, and by determination of the crystal structure of rmGPb in complex with the triazole derivatives the structural basis of their inhibitory efficacy is also elucidated. Our studies revealed that the van der Waals interactions between the aryl moiety and residues in a hydrophobic pocket within the active site are mainly responsible for the variations in the potency of these inhibitors. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. 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.

  12. Development and validation of a rapid, aldehyde dehydrogenase bright-based cord blood potency assay.

    Science.gov (United States)

    Shoulars, Kevin; Noldner, Pamela; Troy, Jesse D; Cheatham, Lynn; Parrish, Amanda; Page, Kristin; Gentry, Tracy; Balber, Andrew E; Kurtzberg, Joanne

    2016-05-12

    Banked, unrelated umbilical cord blood provides access to hematopoietic stem cell transplantation for patients lacking matched bone marrow donors, yet 10% to 15% of patients experience graft failure or delayed engraftment. This may be due, at least in part, to inadequate potency of the selected cord blood unit (CBU). CBU potency is typically assessed before cryopreservation, neglecting changes in potency occurring during freezing and thawing. Colony-forming units (CFUs) have been previously shown to predict CBU potency, defined as the ability to engraft in patients by day 42 posttransplant. However, the CFU assay is difficult to standardize and requires 2 weeks to perform. Consequently, we developed a rapid multiparameter flow cytometric CBU potency assay that enumerates cells expressing high levels of the enzyme aldehyde dehydrogenase (ALDH bright [ALDH(br)]), along with viable CD45(+) or CD34(+) cell content. These measurements are made on a segment that was attached to a cryopreserved CBU. We validated the assay with prespecified criteria testing accuracy, specificity, repeatability, intermediate precision, and linearity. We then prospectively examined the correlations among ALDH(br), CD34(+), and CFU content of 3908 segments over a 5-year period. ALDH(br) (r = 0.78; 95% confidence interval [CI], 0.76-0.79), but not CD34(+) (r = 0.25; 95% CI, 0.22-0.28), was strongly correlated with CFU content as well as ALDH(br) content of the CBU. These results suggest that the ALDH(br) segment assay (based on unit characteristics measured before release) is a reliable assessment of potency that allows rapid selection and release of CBUs from the cord blood bank to the transplant center for transplantation. © 2016 by The American Society of Hematology.

  13. Development and validation of a rapid, aldehyde dehydrogenase bright–based cord blood potency assay

    Science.gov (United States)

    Noldner, Pamela; Troy, Jesse D.; Cheatham, Lynn; Parrish, Amanda; Page, Kristin; Gentry, Tracy; Balber, Andrew E.; Kurtzberg, Joanne

    2016-01-01

    Banked, unrelated umbilical cord blood provides access to hematopoietic stem cell transplantation for patients lacking matched bone marrow donors, yet 10% to 15% of patients experience graft failure or delayed engraftment. This may be due, at least in part, to inadequate potency of the selected cord blood unit (CBU). CBU potency is typically assessed before cryopreservation, neglecting changes in potency occurring during freezing and thawing. Colony-forming units (CFUs) have been previously shown to predict CBU potency, defined as the ability to engraft in patients by day 42 posttransplant. However, the CFU assay is difficult to standardize and requires 2 weeks to perform. Consequently, we developed a rapid multiparameter flow cytometric CBU potency assay that enumerates cells expressing high levels of the enzyme aldehyde dehydrogenase (ALDH bright [ALDHbr]), along with viable CD45+ or CD34+ cell content. These measurements are made on a segment that was attached to a cryopreserved CBU. We validated the assay with prespecified criteria testing accuracy, specificity, repeatability, intermediate precision, and linearity. We then prospectively examined the correlations among ALDHbr, CD34+, and CFU content of 3908 segments over a 5-year period. ALDHbr (r = 0.78; 95% confidence interval [CI], 0.76-0.79), but not CD34+ (r = 0.25; 95% CI, 0.22-0.28), was strongly correlated with CFU content as well as ALDHbr content of the CBU. These results suggest that the ALDHbr segment assay (based on unit characteristics measured before release) is a reliable assessment of potency that allows rapid selection and release of CBUs from the cord blood bank to the transplant center for transplantation. PMID:26968535

  14. Rationale for further medical and health research on high-potency sweeteners.

    Science.gov (United States)

    Schiffman, Susan S

    2012-10-01

    High-potency or artificial sweeteners have historically been considered inert compounds without physiological consequences other than taste sensations. However, recent data suggest that some of these sweeteners have biological effects that may impact human health. Furthermore, there are significant gaps in our current knowledge of the pharmacokinetics of these sweeteners, their potential for "sweetener-drug interactions" and their impact on appetite and body weight regulation. Nine research needs are described that address some of the major unknown issues associated with ingestion of high-potency sweeteners.

  15. 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.

  16. 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...... to 2012, 232 patients underwent RARP. Self-reported continence, erection sufficient for intercourse (ESI) and scores on the five-item version of the International Index of Erectile Function-5 (IIEF-5) were registered by questionnaire and physician's interview preoperatively and at 3, 6 and 12 month follow...

  17. 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

  18. Evaluation of the potency activity of aphrodisiac in Eurycoma longifolia Jack.

    Science.gov (United States)

    Ang, H H; Ikeda, S; Gan, E K

    2001-08-01

    The butanol, methanol, water and chloroform extracts of the roots of Eurycoma longifolia Jack were studied using various tests of potency of treated male rats. The results showed that E. longifolia produced a dose-dependent, recurrent and significant increase in the episodes of penile reflexes as evidenced by increases in quick flips, long flips and erections of the treated male rats during the 30 min observation period. These results provide further evidence that E. longifolia increases the aphrodisiac potency activity in treated animals. Copyright 2001 John Wiley & Sons, Ltd.

  19. Embryonic Stem Cell Culture Conditions Support Distinct States Associated with Different Developmental Stages and Potency

    DEFF Research Database (Denmark)

    Martin Gonzalez, Javier; Morgani, Sophie M; Bone, Robert A

    2016-01-01

    Embryonic stem cells (ESCs) are cell lines derived from the mammalian pre-implantation embryo. Here we assess the impact of derivation and culture conditions on both functional potency and ESC transcriptional identity. Individual ESCs cultured in either two small-molecule inhibitors (2i) or with ......Embryonic stem cells (ESCs) are cell lines derived from the mammalian pre-implantation embryo. Here we assess the impact of derivation and culture conditions on both functional potency and ESC transcriptional identity. Individual ESCs cultured in either two small-molecule inhibitors (2i...

  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

    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...

  1. Antipsychotic-induced extrapyramidal syndromes - Risperidone compared with low- and high-potency conventional antipsychotic drugs

    NARCIS (Netherlands)

    Schillevoort, [No Value; de Boer, A; Herings, RMC; Roos, RAC; Jansen, PAF; Leufkens, HGM

    Aim: To compare the risk of extrapyramidal syndromes (EPS) between patients using risperidone and those using low-potency conventional antipsychotic drugs (APDs) in outpatient clinical practice, as measured by the use of anticholinergic medication. We tried to replicate results from previous

  2. Reduced antimicrobial potencies of oxytetracycline, tylosin, sulfadiazin, streptomycin, ciprofloxacin, and olaquindox due to environmental processes.

    Science.gov (United States)

    Halling-Sørensen, B; Sengeløv, G; Ingerslev, F; Jensen, L B

    2003-01-01

    The stability of oxytetracycline (OTC), tylosin (TYL), sulfadiazin (SDZ), streptomycin (ST), ciprofloxacin (CF) and olaquindox (O) was examined in environmentally relevant matrices, such as soil interstitial water and sewage sludge water. Compounds were assessed in both aerobic (OTC, TYL, SDZ, ST, and CF) and anaerobic experiments (OTC, TYL, and O) using analytical measurements (UV spectrophotometry or HPLC) combined with a growth inhibition pour plate assay using activated sludge bacteria. (OTC was additionally assessed using a soil bacterial assay.) This combination of results enabled the assessment of whether a loss in antibacterial potency was reflected in a similar reduction of substance concentration. If a potency reduction is not reflected in a decreased substance concentration, the results may indicate the formation of less potent degradation products possessing the same chromophoric system (same UV absorbance maximum) as the parent compound. With the exception of ST and CF, the antimicrobial agents generally lost a considerable amount of their antimicrobial potency in aerobic experiments. In the anaerobic experiments having either an experimental duration of 21 or 100 days only OTC retained potency. These results correspond well with the fact that several degradation products were encountered in the study for this compound

  3. IgE-binding potencies of three peach Pru p 1 isoforms

    NARCIS (Netherlands)

    Gao, Zhong-Shan; Zhou, Xiang; Yang, Zhao-Wei; Versteeg, Serge A.; Gao, Ling; Fu, Wan-Yi; Wang, Hui-Ying; Zhou, Jian-Ying; Akkerdaas, Jaap H.; van Ree, Ronald

    2016-01-01

    Pru p 1, the Bet v 1 homologue from peach, has been identified as a clinically relevant allergen. Three isoforms have been described, two in peach fruit (Pru p 1.0101 and Pru p 1.0201) and one in pollen (Pru p 1.0301). The present study aimed to compare their IgE-binding potencies. Three Pru p 1

  4. Sweetness potency and sweetness synergism of sweeteners in milk and coffee systems.

    Science.gov (United States)

    Choi, Ji-Hye; Chung, Seo-Jin

    2015-08-01

    This study investigated the presence of sweetness synergism in milk and instant coffee systems. It consists of three parts: 1) modeling concentration-sweetness intensity curves of sweeteners (stevia, sucralose, xylose, tagatose and erythritol); 2) measuring the sweetness potencies of sweeteners compared to sucrose at wide concentration range; and 3) investigating the presence of sweetness synergisms in binary sweetener mixtures. The panelists evaluated sweetness and other sensory characteristics of sweeteners using descriptive analysis. Based on the modeled curve derived from step 1, the concentration of each sweetener with sweetness intensity equal to 2.5% or 2.8% sucrose was calculated for milk and coffee systems, respectively. For the sweetness synergism study, one type of intense sweetener was mixed with one type of bulk sweetener, each eliciting 2.5% or 2.8% equi-sweetness to sucrose, and compared with 5% sucrose added to a milk system or 5.6% sucrose added to a coffee system. The sweetness potencies of bulk sweeteners generally increased whereas the sweetness potencies of intense sweeteners decreased as the concentration increased. The binary sweetener mixtures mostly showed additivity in milk and suppression in coffee system rather than synergism when the concentration dependent nature of sweetness potency for each sweetener was taken into account. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    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 microM were obtained; however, one compound, nicarbazin exhibited an EC(50)-value above the maximum tested concentration (21 microM, 9.1 mg L(-1))....

  6. 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.

  7. Second generation of hydroxyethylamine BACE-1 inhibitors: optimizing potency and oral bioavailability.

    Science.gov (United States)

    Charrier, Nicolas; Clarke, Brian; Cutler, Leanne; Demont, Emmanuel; Dingwall, Colin; Dunsdon, Rachel; East, Philip; Hawkins, Julie; Howes, Colin; Hussain, Ishrut; Jeffrey, Phil; Maile, Graham; Matico, Rosalie; Mosley, Julie; Naylor, Alan; O'Brien, Alistair; Redshaw, Sally; Rowland, Paul; Soleil, Virginie; Smith, Kathrine J; Sweitzer, Sharon; Theobald, Pam; Vesey, David; Walter, Daryl S; Wayne, Gareth

    2008-06-12

    BACE-1 inhibition has the potential to provide a disease-modifying therapy for the treatment of Alzheimer's disease. Optimization of a first generation of BACE-1 inhibitors led to the discovery of novel hydroxyethylamines (HEAs) bearing a tricyclic nonprime side. These derivatives have nanomolar cell potency and are orally bioavailable.

  8. Social Capital, Team Efficacy and Team Potency: The Mediating Role of Team Learning Behaviors

    Science.gov (United States)

    van Emmerik, Hetty; Jawahar, I. M.; Schreurs, Bert; de Cuyper, Nele

    2011-01-01

    Purpose: Drawing on social capital theory and self-identification theory, this study aims to examine the associations of two indicators of social capital, personal networks and deep-level similarity, with team capability measures of team efficacy and team potency. The central focus of the study is to be the hypothesized mediating role of team…

  9. 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...

  10. 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 ...

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

    Science.gov (United States)

    Teschendorff, Andrew E.; Enver, Tariq

    2017-06-01

    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.

  12. 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 ...

  13. Comparative Elongated Mineral Particle Toxicology & Erionite’s Apparent  High Potency for Inducing Mesothelioma

    Science.gov (United States)

    Recent NHEERL research under EPA's Libby Action Plan has determined that elongated particle relative potency for rat pleural mesothelioma is best predicted on the basis of total external surface area (TSA) of slightly acid leached test samples which simulate particle bio-durabili...

  14. Replacing the NIH test for rabies vaccine potency testing: a synopsis of drivers and barriers

    NARCIS (Netherlands)

    Schiffelers, M.J.; Blaauboer, B.J.; Bakker, W.; Hendriksen, C.F.M.

    Approximately 70% of animal use is utilized to demonstrate quality control of vaccines. Especially rabies vaccine potency testing, using the NIH challenge test, involves objections in terms of scientific relevance, animal welfare concern and costs. Several 3R models have been proposed to refine,

  15. 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.

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

    NARCIS (Netherlands)

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

    2003-01-01

    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

  17. Role of Homologous Fc Fragment in the Potency and Efficacy of Anti‐Botulinum Antibody Preparations

    Directory of Open Access Journals (Sweden)

    Amram Torgeman

    2017-05-01

    Full Text Available The only approved treatment for botulism relies on passive immunity which is mostly based on antibody preparations collected from hyper‐immune horses. The IgG Fc fragment is commonly removed from these heterologous preparations to reduce the incidence of hyper‐sensitivity reactions. New‐generation therapies entering the pipeline are based on a combination of humanized monoclonal antibodies (MAbs, which exhibit improved safety and pharmacokinetics. In the current study, a systematic and quantitative approach was applied to measure the direct contribution of homologous Fc to the potency of monoclonal and polyclonal antitoxin preparations in mice. Homologous Fc increased the potency of three individual anti‐botulinum toxin MAbs by up to one order of magnitude. Moreover, Fc fragment removal almost completely abolished the synergistic potency obtained from a combined preparation of these three MAbs. The MAb mixture neutralized a 400‐mouse median lethal dose (MsLD50 of botulinum toxin, whereas the F(ab′2 combination failed to neutralize 10 MsLD50 of botulinum toxin. Notably, increased avidity did not compensate for this phenomenon, as a polyclonal, hyper‐immune, homologous preparation lost 90% of its potency as well upon Fc removal. Finally, the addition of homologous Fc arms to a heterologous pharmaceutical anti‐botulinum toxin polyclonal horse F(ab′2 preparation improved its efficacy when administered to intoxicated symptomatic mice. Our study extends the aspects by which switching from animal‐based to human‐based antitoxins will improve not only the safety but also the potency and efficacy of passive immunity against toxins.

  18. Evaluation of residual antibacterial potency in antibiotic production wastewater using a real-time quantitative method.

    Science.gov (United States)

    Zhang, Hong; Zhang, Yu; Yang, Min; Liu, Miaomiao

    2015-11-01

    While antibiotic pollution has attracted considerable attention due to its potential in promoting the dissemination of antibiotic resistance genes in the environment, the antibiotic activity of their related substances has been neglected, which may underestimate the environmental impacts of antibiotic wastewater discharge. In this study, a real-time quantitative approach was established to evaluate the residual antibacterial potency of antibiotics and related substances in antibiotic production wastewater (APW) by comparing the growth of a standard bacterial strain (Staphylococcus aureus) in tested water samples with a standard reference substance (e.g. oxytetracycline). Antibiotic equivalent quantity (EQ) was used to express antibacterial potency, which made it possible to assess the contribution of each compound to the antibiotic activity in APW. The real-time quantitative method showed better repeatability (Relative Standard Deviation, RSD 1.08%) compared with the conventional fixed growth time method (RSD 5.62-11.29%). And its quantification limits ranged from 0.20 to 24.00 μg L(-1), depending on the antibiotic. We applied the developed method to analyze the residual potency of water samples from four APW treatment systems, and confirmed a significant contribution from antibiotic transformation products to potent antibacterial activity. Specifically, neospiramycin, a major transformation product of spiramycin, was found to contribute 13.15-22.89% of residual potency in spiramycin production wastewater. In addition, some unknown related substances with antimicrobial activity were indicated in the effluent. This developed approach will be effective for the management of antibacterial potency discharge from antibiotic wastewater and other waste streams.

  19. EMD638683, a novel SGK inhibitor with antihypertensive potency.

    Science.gov (United States)

    Ackermann, Teresa F; Boini, Krishna M; Beier, Norbert; Scholz, Wolfgang; Fuchss, Thomas; Lang, Florian

    2011-01-01

    The serum- and glucocorticoid-inducible kinase 1 (SGK1) is transcriptionally upregulated by mineralocorticoids and activated by insulin. The kinase enhances renal tubular Na(+)-reabsorption and accounts for blood pressure increase following high salt diet in mice made hyperinsulinemic by dietary fructose or fat. The present study describes the in vitro and in vivo efficacy of a novel SGK1 inhibitor (EMD638683). EMD638683 was tested in vitro by determination of SGK1-dependent phosphorylation of NDRG1 (N-Myc downstream-regulated gene 1) in human cervical carcinoma HeLa-cells. In vivo EMD638683 (4460 ppm in chow, i.e. approx. 600 mg/kg/day) was administered to mice drinking tap water or isotonic saline containing 10% fructose. Blood pressure was determined by the tail cuff method, and urinary electrolyte (flame photometry) concentrations determined in metabolic cages. In vitro testing disclosed EMD638683 as a SGK1 inhibitor with an IC50 of 3 μM. Within 24 hours in vivo EMD638683 treatment significantly decreased blood pressure in fructose/saline-treated mice but not in control animals or in SGK1 knockout mice. EMD638683 failed to alter the blood pressure in SGK1 knockout mice. Following chronic (4 weeks) fructose/high salt treatment, additional EMD638683 treatment again decreased blood pressure. EMD638683 thus abrogates the salt sensitivity of blood pressure in hyperinsulinism without appreciably affecting blood pressure in the absence of hyperinsulinism. EMD638683 tended to increase fluid intake and urinary excretion of Na(+), significantly increased urinary flow rate and significantly decreased body weight. EMD638683 could serve as a template for drugs counteracting hypertension in individuals with type II diabetes and metabolic syndrome. Copyright © 2011 S. Karger AG, Basel.

  20. 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.

  1. Potency trends of Δ9-THC and other cannabinoids in confiscated cannabis preparations from 1993 to 2008.

    Science.gov (United States)

    Mehmedic, Zlatko; Chandra, Suman; Slade, Desmond; Denham, Heather; Foster, Susan; Patel, Amit S; Ross, Samir A; Khan, Ikhlas A; ElSohly, Mahmoud A

    2010-09-01

    The University of Mississippi has a contract with the National Institute on Drug Abuse (NIDA) to carry out a variety of research activities dealing with cannabis, including the Potency Monitoring (PM) program, which provides analytical potency data on cannabis preparations confiscated in the United States. This report provides data on 46,211 samples seized and analyzed by gas chromatography-flame ionization detection (GC-FID) during 1993-2008. The data showed an upward trend in the mean Δ(9)-tetrahydrocannabinol (Δ(9)-THC) content of all confiscated cannabis preparations, which increased from 3.4% in 1993 to 8.8% in 2008. Hashish potencies did not increase consistently during this period; however, the mean yearly potency varied from 2.5-9.2% (1993-2003) to 12.0-29.3% (2004-2008). Hash oil potencies also varied considerably during this period (16.8 ± 16.3%). The increase in cannabis preparation potency is mainly due to the increase in the potency of nondomestic versus domestic samples. © 2010 American Academy of Forensic Sciences.

  2. Potency determination of inactivated H7 influenza vaccines using monoclonal antibody-based ELISA and biolayer interferometry assays.

    Science.gov (United States)

    Vasudevan, Anupama; Woerner, Amy; Schmeisser, Falko; Verma, Swati; Williams, Ollie; Weir, Jerry P

    2018-03-01

    The single radial immunodiffusion (SRID) assay, the accepted method for determining potency of inactivated influenza vaccines, measures an immunogenic form of the influenza hemagglutinin. Nevertheless, alternative methods for measuring vaccine potency have been explored to address some of the weaknesses of the SRID assay, including limited sensitivity and the requirement for large amounts of standardized reagents. Monoclonal antibody (mAb)-based potency assays also have the ability to detect and measure relevant immunogenic forms of HA. The objective of this study was to continue evaluation of mAb-based alternative methods for measuring the potency of inactivated influenza vaccines, focusing on A(H7N9) pandemic influenza vaccines. Several murine mAbs that recognize different epitopes on the H7 hemagglutinin (HA) were identified and characterized. These mAbs were evaluated in both a mAb-capture ELISA and a mAb-based biolayer interferometry (BLI) assay. Results indicated that potency of inactivated A(H7N9) vaccines, including vaccine samples that were stressed by heat treatment, measured by either alternative method correlated well with potency determined by the traditional SRID potency assay. The availability of multiple H7 mAbs, directed to different HA epitopes, provides needed redundancy in the potency analysis as A(H7N9) viruses continue to evolve antigenically and suggests the importance of having a broad, well-characterized panel of mAbs available for development of vaccines against influenza strains with pandemic potential. In addition, the results highlight the potential of mAb-based platform such as ELISA and BLI for development as alternative methods for determining the potency of inactivated influenza vaccines. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.

  3. The Potency of Hyaluronan of Different Molecular Weights in the Stimulation of Blood Phagocytes

    Directory of Open Access Journals (Sweden)

    Barbora Safrankova

    2010-01-01

    Full Text Available The regulatory functions of glycosaminoglycan hyaluronan (HA are suggested to be dependent on its molecular weight (MW. Proinflammatory and stimulatory effects are proposed mainly for the low MW HA. However, the complex response of blood phagocytes to HA of different MW is unclear. Herein, the effects of highly purified HA of precisely defined MW (52, 250, and 970 kDa on human blood phagocytes were tested. All MW HA activated blood phagocytes, including the spontaneous production of ROS, degranulation, and the production of tumor necrosis factor alpha, with low MW HA 52 kDa having the highest potency and high MW HA 970 kDa having the lowest potency. Interestingly, HA inhibited ROS production stimulated by opsonized zymosan particles and, in contrast, potentiated starch-activated ROS production, mostly independent of MW. Data showed a significant effect of HA of different MW on blood phagocytes, including high MW HA.

  4. The potency of hyaluronan of different molecular weights in the stimulation of blood phagocytes.

    Science.gov (United States)

    Safrankova, Barbora; Gajdova, Silvie; Kubala, Lukas

    2010-01-01

    The regulatory functions of glycosaminoglycan hyaluronan (HA) are suggested to be dependent on its molecular weight (MW). Proinflammatory and stimulatory effects are proposed mainly for the low MW HA. However, the complex response of blood phagocytes to HA of different MW is unclear. Herein, the effects of highly purified HA of precisely defined MW (52, 250, and 970  kDa) on human blood phagocytes were tested. All MW HA activated blood phagocytes, including the spontaneous production of ROS, degranulation, and the production of tumor necrosis factor alpha, with low MW HA 52  kDa having the highest potency and high MW HA 970  kDa having the lowest potency. Interestingly, HA inhibited ROS production stimulated by opsonized zymosan particles and, in contrast, potentiated starch-activated ROS production, mostly independent of MW. Data showed a significant effect of HA of different MW on blood phagocytes, including high MW HA.

  5. 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

    BACKGROUND: Acceleromyography (AMG) is increasingly being used in neuromuscular research, including in studies establishing the potency of neuromuscular blocking and reversal agents. However, AMG is insufficiently validated for use interchangeably with the gold standard, mechanomyography (MMG...... 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...... difference between AMG and MMG is so small that it justifies AMG to be used for establishing the potency of neuromuscular blocking agents. However, the wide CIs show that we cannot rule out a 13% higher ED(50) and a 26% higher ED(95) for AMG....

  6. Evaluating the Effect of Peptoid Lipophilicity on Antimicrobial Potency, Cytotoxicity, and Combinatorial Library Design.

    Science.gov (United States)

    Turkett, Jeremy A; Bicker, Kevin L

    2017-04-10

    Growing prevalence of antibiotic resistant bacterial infections necessitates novel antimicrobials, which could be rapidly identified from combinatorial libraries. We report the use of the peptoid library agar diffusion (PLAD) assay to screen peptoid libraries against the ESKAPE pathogens, including the optimization of assay conditions for each pathogen. Work presented here focuses on the tailoring of combinatorial peptoid library design through a detailed study of how peptoid lipophilicity relates to antibacterial potency and mammalian cell toxicity. The information gleaned from this optimization was then applied using the aforementioned screening method to examine the relative potency of peptoid libraries against Staphylococcus aureus, Acinetobacter baumannii, and Enterococcus faecalis prior to and following functionalization with long alkyl tails. The data indicate that overall peptoid hydrophobicity and not simply alkyl tail length is strongly correlated with mammalian cell toxicity. Furthermore, this work demonstrates the utility of the PLAD assay in rapidly evaluating the effect of molecular property changes in similar libraries.

  7. Evaluation of two serological methods for potency testing of whole cell pertussis vaccines.

    Science.gov (United States)

    von Hunolstein, C; Gomez Miguel, M J; Pezzella, C; Scopetti, F; Behr-Gross, M-E; Halder, M; Hoffmann, S; Levels, L; van der Gun, J; Hendriksen, C

    2008-12-01

    The European Pharmacopoeia (Ph. Eur.) and the World Health Organization (WHO) require the performance of extensive quality control testing including a potency test before a vaccine batch is released for human use. Whole cell pertussis (wP) vaccine potency is assessed by a mouse protection test (MPT) based on the Kendrick test. This test compares the vaccine dose necessary to protect 50% of mice against the effect of a lethal intracerebral dose of Bordetella pertussis and the dose of a suitable reference vaccine needed to give the same protection level. Due to the large variability in the results of this test and the severe distress which is inflicted on the many animals involved, its replacement by an alternative method is highly desirable. At the initiative of the European Directorate for the Quality of Medicines and HealthCare (EDQM) of the Council of Europe, in collaboration with the WHO and the In-vitro toxicology Unit/European Centre for the Validation of Alternative Methods (ECVAM) of the European Commission (EC) Joint Research Centre-Institute for Health and Consumer Protection (JRC-IHCP), wP vaccine specialists from all over the world were invited to present an overview of candidate alternatives at a symposium organised in Geneva (Switzerland) in March 2005. Although no alternative method was found suitable for immediate implementation of batch potency control, the Pertussis Serological Potency Test (PSPT), initially developed in mice and recently transferred to guinea pigs (gps), was identified as a model of interest. Using the PSPT in gps to test several components of combined vaccines such as Diphtheria-Tetanus-wP vaccines in the same animal series would allow further implementation of the European 3Rs policy to batch potency control, by additional method refinement and reduction of animal use. The present study evaluated 2 features of the serological response to wP vaccination: 1) the overall antibody response as measured by a "whole cell" ELISA (PSPT

  8. Fish model for assessing the in vivo estrogenic potency of the mycotoxin zearalenone and its metabolites.

    Science.gov (United States)

    Arukwe, A; Grotmol, T; Haugen, T B; Knudsen, F R; Goksøyr, A

    1999-09-15

    The in vivo estrogenic potency of zearalenone (ZEA), a mycotoxin produced by different strains of Fusarium fungi, and its metabolites (alpha- and beta-zearalenol), have been studied in fish. Estrogenicity was evaluated using an in vitro competitive receptor binding assay and in vivo induction of vitellogenesis and zonagenesis, two estrogen receptor (ER)-mediated responses that are integral aspects of fish oogenesis. The ER binding affinities of alpha-zearalenol and ZEA in rainbow trout (Oncorhynchus mykiss) were approximately 1/150 and 1/300 to that of estradiol, respectively. Juvenile salmon (Salmo salar) were exposed to a single intraperitoneal injection of ZEA, alpha-zearalenol and beta-zearalenol (each at 1 and 10 mg/kg) and compared to fish injected with estradiol-17 beta (E2; 5 mg/kg) and controls. Using indirect enzyme-linked immunosorbent assay (ELISA) with homologous antibodies, a dose-dependent induction of vitellogenin (Vtg) and eggshell zona radiata proteins (Zr-proteins) were observed 7 days after exposure to ZEA and alpha-zearalenol. beta-Zearalenol did not elevate plasma Vtg levels, but a non-significant elevation of plasma Zr-proteins levels was observed at the highest dose (10 mg/kg). Generally, alpha-zearalenol and ZEA possess estrogenic potencies that are approximately 50% compared to that of E2, and their order of estrogenic potency (in both in vitro receptor competitive binding and in vivo induction of Vtg and Zr-proteins levels) is: alpha-zearalenol > ZEA > beta-zearalenol. Our results show that blood plasma analysis of Vtg and Zr-proteins levels provides a suitable in vivo fish model for assessing the estrogenic potencies of ZEA and its metabolites.

  9. BACE-1 inhibitors part 3: identification of hydroxy ethylamines (HEAs) with nanomolar potency in cells.

    Science.gov (United States)

    Beswick, Paul; Charrier, Nicolas; Clarke, Brian; Demont, Emmanuel; Dingwall, Colin; Dunsdon, Rachel; Faller, Andrew; Gleave, Robert; Hawkins, Julie; Hussain, Ishrut; Johnson, Christopher N; MacPherson, David; Maile, Graham; Matico, Rosalie; Milner, Peter; Mosley, Julie; Naylor, Alan; O'Brien, Alistair; Redshaw, Sally; Riddell, David; Rowland, Paul; Skidmore, John; Soleil, Virginie; Smith, Kathrine J; Stanway, Steven; Stemp, Geoffrey; Stuart, Alistair; Sweitzer, Sharon; Theobald, Pam; Vesey, David; Walter, Daryl S; Ward, John; Wayne, Gareth

    2008-02-01

    This article is focusing on further optimization of previously described hydroxy ethylamine (HEA) BACE-1 inhibitors obtained from a focused library with the support of X-ray crystallography. Optimization of the non-prime side of our inhibitors and introduction of a 6-membered sultam substituent binding to Asn-294 as well as a fluorine in the C-2 position led to derivatives with nanomolar potency in cell-based assays.

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

    OpenAIRE

    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....

  11. 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

    potency. We find that the ratios of BaP/ mutagenicity and PAH/mutagenicity are highly variable. The processes responsible for the variation are formation and degradation of mutagens and transport of polluted air masses from heavily industrialized regions, Air masses from Central Europe are shown...... been used in the past as an indicator of the carcinogenic risk of airborne particles, it is suggested that the cancer risk of air pollution has to be re-evaluated....

  12. 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.

  13. Introduction of mismatches in a random shRNA-encoding library improves potency for phenotypic selection.

    Directory of Open Access Journals (Sweden)

    Yongping Wang

    Full Text Available RNA interference (RNAi is a mechanism for interfering with gene expression through the action of small, non-coding RNAs. We previously constructed a short-hairpin-loop RNA (shRNA encoding library that is random at the nucleotide level [1]. In this library, the stems of the hairpin are completely complementary. To improve the potency of initial hits, and therefore signal-to-noise ratios in library screening, as well as to simplify hit-sequence retrieval by PCR, we constructed a second-generation library in which we introduced random mismatches between the two halves of the stem of each hairpin, on a random template background. In a screen for shRNAs that protect an interleukin-3 (IL3 dependent cell line from IL3 withdrawal, our second-generation library yielded hit sequences with significantly higher potencies than those from the first-generation library in the same screen. Our method of random mutagenesis was effective for a random template and is likely suitable, therefore, for any DNA template of interest. The improved potency of our second-generation library expands the range of possible unbiased screens for small-RNA therapeutics and biologic tools.

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. Circadian Gene CLOCK Affects Drug-Resistant Gene Expression and Cell Proliferation in Ovarian Cancer SKOV3/DDP Cell Lines Through Autophagy.

    Science.gov (United States)

    Sun, Yang; Jin, Long; Sui, Yu-Xia; Han, Li-Li; Liu, Jia-Hua

    2017-05-01

    Abnormal autophagy regulation affects the chemoresistance of ovarian cancer, during which the circadian gene clock may play a major role. In this study, RNA interference plasmid pSUPER-Clock and overexpression plasmid pcDNA3.1-Clock of CLOCK were used to stably transfect the SKOV3/DDP cells by lipofection. Upon screening, the in vitro transfected cell lines with pSUPER-Clock, the autophagy level, and G 0 /G 1 phase cells were significantly reduced, and the expression levels of Clock, LC3, P-gp, and MRP2 were inhibited. In contrast, the autophagy level and G 0 /G 1 phase cells in cell lines transfected with pcDNA3.1-Clock were significantly increased, and the expressions of Clock, LC3, P-gp, and MRP2 were enhanced. In comparison with the untransfected control group showed the percentage of apoptotic cells in SKOV3/DDP cell lines of Clock interfering expression group after cisplatin treatment was significantly increased while the survival was substantially reduced. These results indicated that inhibiting the circadian gene Clock expression can reverse the cisplatin resistance of ovarian cancer SKOV3/DDP cell lines by affecting the protein expression of drug resistance genes during which autophagy plays an important role. The CLOCK gene may be designated as a novel candidate for targeted gene therapy in drug-resistant ovarian cancer.

  20. 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

  1. Proportion of patients in south London with first-episode psychosis attributable to use of high potency cannabis: a case-control study.

    Science.gov (United States)

    Di Forti, Marta; Marconi, Arianna; Carra, Elena; Fraietta, Sara; Trotta, Antonella; Bonomo, Matteo; Bianconi, Francesca; Gardner-Sood, Poonam; O'Connor, Jennifer; Russo, Manuela; Stilo, Simona A; Marques, Tiago Reis; Mondelli, Valeria; Dazzan, Paola; Pariante, Carmine; David, Anthony S; Gaughran, Fiona; Atakan, Zerrin; Iyegbe, Conrad; Powell, John; Morgan, Craig; Lynskey, Michael; Murray, Robin M

    2015-03-01

    The risk of individuals having adverse effects from drug use (eg, alcohol) generally depends on the frequency of use and potency of the drug used. We aimed to investigate how frequent use of skunk-like (high-potency) cannabis in south London affected the association between cannabis and psychotic disorders. We applied adjusted logistic regression models to data from patients aged 18-65 years presenting to South London and Maudsley NHS Foundation Trust with first-episode psychosis and population controls recruited from the same area of south London (UK) to estimate the effect of the frequency of use, and type of cannabis used on the risk of psychotic disorders. We then calculated the proportion of new cases of psychosis attributable to different types of cannabis use in south London. Between May 1, 2005, and May 31, 2011, we obtained data from 410 patients with first-episode psychosis and 370 population controls. The risk of individuals having a psychotic disorder showed a roughly three-times increase in users of skunk-like cannabis compared with those who never used cannabis (adjusted odds ratio [OR] 2·92, 95% CI 1·52-3·45, p=0·001). Use of skunk-like cannabis every day conferred the highest risk of psychotic disorders compared with no use of cannabis (adjusted OR 5·4, 95% CI 2·81-11·31, p=0·002). The population attributable fraction of first-episode psychosis for skunk use for our geographical area was 24% (95% CI 17-31), possibly because of the high prevalence of use of high-potency cannabis (218 [53%] of 410 patients) in our study. The ready availability of high potency cannabis in south London might have resulted in a greater proportion of first onset psychosis cases being attributed to cannabis use than in previous studies. UK National Institute of Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health, SLaM and the Institute of Psychiatry at King's College London, Psychiatry Research Trust, Maudsley Charity Research Fund, and

  2. Bayesian approach to potency estimation for aquatic toxicology experiments when a toxicant affects both fecundity and survival.

    Science.gov (United States)

    Zhang, Jing; Bailer, A John; Oris, James T

    2012-08-01

    Chemicals in aquatic systems may impact a variety of endpoints including mortality, growth, or reproduction. Clearly, growth or reproduction will only be observed in organisms that survive. Because it is common to observe mortality in studies focusing on the reproduction of organisms, especially in higher concentration conditions, the resulting observed numbers of young become a mixture of zeroes and positive counts. Zeroes are recorded for organisms that die before having any young and living organisms with no offspring. Positive counts are recorded for living organisms with offspring. Thus, responses reflect both fecundity and mortality of the organisms used in such tests. In the present study, the authors propose the estimation of the concentration associated with a specified level of reproductive inhibition (RIp) using a Bayesian zero-inflated Poisson (ZIP) regression model. This approach allows any prior information and expert knowledge about the model parameters to be incorporated into the regression coefficients or RIp estimation. Simulation studies are conducted to compare the Bayesian ZIP regression model and classical methods. The Bayesian estimator outperforms the frequentist alternative by producing more precise point estimates with smaller mean square differences between RIp estimates and true values, narrower interval estimates with better coverage probabilities. The authors also applied their proposed model to a study of Ceriodaphnia dubia exposed to a test toxicant. Copyright © 2012 SETAC.

  3. 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.

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

    Science.gov (United States)

    Cheng, Bing-Ho; Sheen, Lee-Yan; Chang, Shang-Tzen

    2015-01-01

    Cinnamomum osmophloeum ct. linalool ( 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.

  5. 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.

    Science.gov (United States)

    Strikwold, Marije; Woutersen, Ruud A; Spenkelink, Bert; Punt, Ans; Rietjens, Ivonne M C M

    2012-09-03

    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 EST was compared to in vivo embryotoxic potency data obtained from literature and to the potency ranking defined in the in vitro whole embryo culture (WEC) assay. From the results obtained it appears that the EST was able to identify the embryotoxic potential for p-substituted phenols, providing an identical potency ranking compared to the WEC assay. However, the EST was not able to predict an accurate ranking for the phenols compared to their potency observed in vivo. Only phenol, the least potent compound within this series, was correctly ranked. Furthermore, p-mercaptophenol was correctly identified as a relative potent congener of the phenols tested, but its ranking was distorted by p-heptyloxyphenol, of which the toxicity was overestimated in the EST. It is concluded that when attempting to explain the observed disparity in potency rankings between in vitro and in vivo embryotoxicity, the in vitro models should be combined with a kinetic model describing in vivo absorption, distribution, metabolism and excretion processes of the compounds. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  6. A Novel Lack-of-Fit Assessment as a System Suitability Test for Potency Assays.

    Science.gov (United States)

    Li, Ruojia; Cai, Weiguo; Zocher, Marcel

    2017-01-01

    Bioassay data analysis is used to determine the potency of protein therapeutics. To properly determine potency, the experimental data need to be fitted to a model that adequately describes the observed dose-response relationship. Typical models include 4-parameter logistic curve fits, 5-parameter logistic curve fits or parallel line analysis. Lack-of-fit assessment can be used as a measure of potency assay system suitability to ensure appropriate closeness of the chosen model fit to the experimental data. We present a novel lack-of-fit approach that overcomes the shortcomings of previously described lack-of-fit tests, such as the conventional analysis of variance (ANOVA) F-test and the lack-of-fit sum of squares test. Simulation studies and examples are used to assess the performance of the new lack-of-fit test. The results show that the described lack-of-fit approach can effectively reject poorly fitted data while retaining well-fitted data, and has advantages in potency assay applications where instrument-to-instrument variability in absolute readout is expected. LAY ABSTRACT: Potency assays are analytical procedures used for characterization as well as release and stability analysis in drug development and for approved products. Dose-response data generated from a drug sample and a well-characterized reference standard are evaluated to determine the potency of the drug sample relative to the reference standard. In order to obtain a potency determination, dose-response data need to be fitted to a proper model that adequately describes the observed dose-response relationship. There are different options described to assess the goodness-of-fit of the data. One approach is the goodness-of-fit assessment based on F-test. This approach compares the lack-of-fit error (representing the discrepancy between observed data and fitted curve) to the pure error (representing the random noise between replicate measurement) to determine if the observed lack-of-fit error can be

  7. 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

  8. 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

  9. 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.

  10. Diversification of Food Consumption for Food Security Based on Local Potency at Household Level in Semin, Gunung Kidul

    OpenAIRE

    Ni, Made Suyastiri.YP

    2008-01-01

    The purpose of the research is to investigate and analyze factors influecing consumption diversification system based on local potency to create household food security. This research uses descriptive method from survey result.Research area is determined by purposive method and household sample is taken by proportional stratified random sampling with 50 households. The result of this research indicates that staple food based on local potency is still dominated by rice followed by cassava and ...

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Moeller K.

    2014-06-01

    Full Text Available 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 is to establish a mean potency, a yield estimate for professionally grown plants, and an assessment of how „professionalism” applies to domestic cultivation. We find a mean THC content in our sample normally distributed around 12% for sinsemilla (n=35 and 11.7% for resin (n=99. This is markedly higher than the assumption of THC content in sinsemilla between 6-8% as is currently applied in Norway and Sweden. It is also higher than the previous estimate of resin potency. The yield in sinsemilla plants is found to be 46 grams per plant. This is much lower than the estimate applied in criminal cases, which indicates 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 thresholds between the (various grades of illicit drug crimes in the national legal systems. Finally, we introduce the nationality of the gardener as an indication of professionalism in combination with the equipment found on site. We conclude that proportionality in criminal sanctioning of large-scale cannabis cases would improve by applying a 1:1 potency level between sinsemilla and resin.

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

    Science.gov (United States)

    Hamers, Timo; van den Brink, Paul J; Mos, Lizzy; van der Linden, Sander C; Legler, Juliette; Koeman, Jan H; Murk, Albertinka J

    2003-01-01

    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 and 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 than in and . 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 aquatic organisms and was highest in . Although estrogenic potency of rainwater correlated with OC concentrations, the ER-CALUX responses could not be attributed to

  14. 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.

  15. 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....

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. Gestodene: a review of its pharmacology, potency and tolerability in combined contraceptive preparations.

    Science.gov (United States)

    Stanczyk, Frank Z; Archer, David F

    2014-04-01

    Combined progestin-estrogen pills are an established and reliable contraceptive option used by women worldwide. Combined oral contraceptives (COCs) containing the progestins--gestodene, desogestrel or norgestimate--were developed to minimize androgenic side effects and are considered an effective, well-tolerated contraceptive option. Gestodene achieves contraceptive efficacy with the lowest dose of any progestin in a COC, and has an established and favorable short- and long-term tolerability profile. In this review we present an overview of the pharmacology, potency and tolerability of gestodene. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Development of quantitative structure-activity relationship (QSAR) models to predict the carcinogenic potency of chemicals. II. Using oral slope factor as a measure of carcinogenic potency.

    Science.gov (United States)

    Wang, Nina Ching Yi; Venkatapathy, Raghuraman; Bruce, Robert Mark; Moudgal, Chandrika

    2011-03-01

    The overall risk associated with exposure to a chemical is determined by combining quantitative estimates of exposure to the chemical with their known health effects. For chemicals that cause carcinogenicity, oral slope factors (OSFs) and inhalation unit risks are used to quantitatively estimate the carcinogenic potency or the risk associated with exposure to the chemical by oral or inhalation route, respectively. Frequently, there is a lack of animal or human studies in the literature to determine OSFs. This study aims to circumvent this problem by developing quantitative structure-activity relationship (QSAR) models to predict the OSFs of chemicals. The OSFs of 70 chemicals based on male/female human, rat, and mouse bioassay data were obtained from the United States Environmental Protection Agency's Integrated Risk Information System (IRIS) database. A global QSAR model that considered all 70 chemicals as well as species and/or sex-specific QSARs were developed in this study. Study results indicate that the species and sex-specific QSARs (r(2)>0.8, q(2)>0.7) had a better predictive abilities than the global QSAR developed using data from all species and sexes (r(2)=0.77, q(2)=0.73). The QSARs developed in this study were externally validated, and demonstrated reasonable predictive abilities. Copyright © 2010 Elsevier Inc. All rights reserved.

  2. 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.

  3. G-protein based ELISA as a potency test for rabies vaccines.

    Science.gov (United States)

    Chabaud-Riou, Martine; Moreno, Nadège; Guinchard, Fabien; Nicolai, Marie Claire; Niogret-Siohan, Elisabeth; Sève, Nicolas; Manin, Catherine; Guinet-Morlot, Françoise; Riou, Patrice

    2017-03-01

    The NIH test is currently used to assess the potency of rabies vaccine, a key criterion for vaccine release. This test is based on mice immunization followed by intracerebral viral challenge. As part of global efforts to reduce animal experimentation and in the framework of the development of Sanofi Pasteur next generation, highly-purified vaccine, produced without any material of human or animal origin, we developed an ELISA as an alternative to the NIH test. This ELISA is based on monoclonal antibodies recognizing specifically the native form of the viral G-protein, the major antigen that induces neutralizing antibody response to rabies virus. We show here that our ELISA is able to distinguish between potent and different types of sub-potent vaccine lots. Satisfactory agreement was observed between the ELISA and the NIH test in the determination of the vaccine titer and their capacity to discern conform from non-conform batches. Our ELISA meets the criteria for a stability-indicating assay and has been successfully used to develop the new generation of rabies vaccine candidates. After an EPAA international pre-collaborative study, this ELISA was selected as the assay of choice for the EDQM collaborative study aimed at replacing the rabies vaccine NIH in vivo potency test. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. 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.

  5. Potency of marbofloxacin for pig pneumonia pathogens Actinobacillus pleuropneumoniae and Pasteurella multocida: Comparison of growth media.

    Science.gov (United States)

    Dorey, L; Hobson, S; Lees, P

    2017-04-01

    Pharmacodynamic properties of marbofloxacin were established for six isolates each of the pig respiratory tract pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida. Three in vitro indices of potency were determined; Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and Mutant Prevention Concentration (MPC). For MIC determination Clinical Laboratory Standards Institute guidelines were modified in three respects: (1) comparison was made between two growth media, an artificial broth and pig serum; (2) a high inoculum count was used to simulate heavy clinical bacteriological loads; and (3) five overlapping sets of two-fold dilutions were used to improve accuracy of determinations. Similar methods were used for MBC and MPC estimations. MIC and MPC serum:broth ratios for A. pleuropneumoniae were 0.79:1 and 0.99:1, respectively, and corresponding values for P. multocida were 1.12:1 and 1.32:1. Serum protein binding of marbofloxacin was 49%, so that fraction unbound (fu) serum MIC values were significantly lower than those predicted by correction for protein binding; fu serum:broth MIC ratios were 0.40:1 (A. pleuropneumoniae) and 0.50:1 (P. multocida). For broth, MPC:MIC ratios were 13.7:1 (A. pleuropneumoniae) and 14.2:1 (P. multocida). Corresponding ratios for serum were similar, 17.2:1 and 18.8:1, respectively. It is suggested that, for dose prediction purposes, serum data might be preferable to potency indices measured in broths. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. 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.

  7. 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

  8. Relative potency as a means of evaluating ELF (Extremely Low Frequency) health risks

    Energy Technology Data Exchange (ETDEWEB)

    Easterly, C.E.; Glass, L.R.

    1990-09-01

    In the 1970's, a variety of developments took place to heightened public and scientific interest in electromagnetic fields. During this time, biological studies of nonionizing electromagnetic fields were taking place, but no clear evidence of risks to public health was identified. Then came the surprising epidemiological finding suggesting that 60 Hz magnetic fields may be related to some childhood leukemias. Our particular interest at ORNL was how to interpret the available data with respect to human exposures to the nearly ubiquitous fields. A review of the available data showed that consistent biological effects were difficult to identify. Classical toxicological tests used in chemical risk assessment had not been performed with Extremely Low Frequency (ELF) fields but rather a wide range of mechanistic studies had been pursued. To evaluate the level of anticipated hazard or risk there was neither a mechanistic understanding nor a consistent phenomenological outcome. A risk evaluation normally requires one or the other of these two types of information. Two quite different approaches were pursued: meta-analysis and relative potency. The first of these is a method to combine data from similar experiments to enhance the relative statistical power of a collection of small sample size studies, and will not be discussed further. The second, relative potency, will be the focus of this paper. 20 refs., 2 figs.

  9. A fully validated microbiological assay to evaluate the potency of ceftriaxone sodium

    Directory of Open Access Journals (Sweden)

    Maria Luisa Manfio

    2013-12-01

    Full Text Available Ceftriaxone (CFTX sodium is a third-generation, broad-spectrum cephalosporin that is resistant to beta-lactamases. An alternative bioassay for the assessment of the potency of this drug in pharmaceutical formulations has not been previously reported. Thus, this paper reports the development and full validation of a 3 x 3 agar diffusion bioassay using a cylinder-plate method to quantify CFTX sodium in pharmaceutical samples. The strain Staphylococcus aureus ATCC 6538P was used as the test microorganism, and the results of the proposed bioassay displayed high linearity, precision, accuracy, specificity and robustness. All potency results were statistically analyzed using an analysis of variance (ANOVA and were found to be linear (r=0.99999 in the range of 16-64 µg/mL, accurate (100.5%, and precise [repeatability: relative standard deviation (RSD=1.4%; intermediate precision: between-day RSD=2.1% and between-analyst RSD=2.5%]. The specificity of the bioassay was determined by evaluating a degraded sample (50 ºC at 0, 24 and 48 hours as compared against the results from the pharmacopeial liquid chromatography method for CFTX. The results validated the proposed microbiological assay, which allows reliable quantitation of CFTX in pharmaceutical samples. Moreover, it is a useful, simple and low-cost alternative method for monitoring the quality of this medicine.

  10. Successful prevalidation of the slug mucosal irritation test to assess the eye irritation potency of chemicals.

    Science.gov (United States)

    Adriaens, E; Bytheway, H; De Wever, B; Eschrich, D; Guest, R; Hansen, E; Vanparys, P; Schoeters, G; Warren, N; Weltens, R; Whittingham, A; Remon, J P

    2008-08-01

    A previous 'in house' validation study showed that the SMI assay can be used as an alternative to the in vivo Draize eye irritation test. The aim of this multi-centre study with four participating laboratories was to assess the transferability and inter-laboratory variability of the assay using 20 reference chemicals covering the whole irritancy range. The eye irritation potency of the chemicals was assessed by measuring the amount of mucus produced during a 60-min contact period with a 1% dilution, and a second 60-min treatment with a 3.5% dilution. After each contact period the protein release from the mucosal surface was measured. Linear discriminant equations were used to convert the results into the corresponding EU eye irritation categories (NI, R36 and R41). All the non-irritants were predicted correctly by the four laboratories resulting in a 100% specificity. For the R36 compounds a correct classification rate of 89% (VITO) and 100% (SPL, JNJ and UGent) was obtained. The R41 compounds were classified correctly in 78% of the cases for VITO, 89% for SPL and JNJ and 100% for UGent. We can conclude that the SMI assay is a relevant, easily transferable and reproducible alternative to predict the eye irritation potency of chemicals.

  11. Modular Assembly of Allosteric MEK Inhibitor Structural Elements Unravels Potency and Feedback-Modulation Handles.

    Science.gov (United States)

    Hartung, Ingo V; Pühler, Florian; Neuhaus, Roland; Scholz, Arne; Siemeister, Gerhard; Geisler, Jens; Hillig, Roman C; von Ahsen, Oliver; Hitchcock, Marion

    2015-12-01

    Having recently identified a so-far unexplored area adjacent to the known binding site of allosteric mitogen-activated protein kinase kinase (MEK) inhibitors, we now report an extension of these studies by combining our new side chains with different MEK inhibitor cores in a modular manner. Replacement of the amide headgroup with inverse sulfonamides resulted in the identification of new MEK inhibitors with at least 10-fold higher cellular potency against K-Ras-mutated tumor cells. A selected inhibitor from this new series retained the favorable pharmacokinetic profile of its predecessor in rodent and non-rodent species and displayed significant in vivo efficacy at once-daily oral doses of 0.25-1 mg kg(-1) in a K-Ras-mutated xenograft model. The brain penetration potential of this analogue was significantly attenuated relative to PD325901. In a second series, the central fluorophenyl core was replaced by a pyridine moiety which gave rise to a similar boost in cellular potency. Most notably, analogues from this second series do not show MEK feedback phosphorylation in K-Ras-mutated A549 cells. Our results complement recent reports on the structural intricacies of MEK-Raf feedback interactions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Effect of volume of solution per cylinder on estimation of antibiotic potency in diffusion assay.

    Science.gov (United States)

    Ragheb, H S

    1988-01-01

    The volume of antibiotic solutions in cylinders used for diffusion assays is assumed to have no significant effect on estimation of potency. The size of zones of inhibition from cylinders containing 0.10, 0.20, and 0.30 mL of sample solution was compared with zones of inhibition from cylinders containing 0.20 mL of standard solutions. For zinc bacitracin, chlortetracycline.HCl, oxytetracycline, lincomycin.HCl, monensin Na, neomycin sulfate, K penicillin, streptomycin sulfate, and tylosin, the percent recovery (95-102) was optimum when both standard and sample cylinders contained the same volume (0.20 mL/cylinder). At 0.30 mL/cylinder for sample and 0.20 mL for standard solutions, there was a positive bias in potency of about 50%. At 0.10 mL/cylinder, there was a negative bias of approximately 25% except for neomycin, monensin, and bacitracin. For these antibiotics, the bias was about -50%. For hygromycin B, variation in volume of solution per cylinder has little effect on assay results. Experiments on commercial feeds and premixes gave essentially the same results as for the standard solutions experiments.

  13. 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.

  14. 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.

  15. 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.

  16. Potency of energy saving and emission reduction from lighting system in residential sector of Indonesia

    Science.gov (United States)

    Ambarita, H.

    2018-03-01

    The Government of Indonesia (GoI) has a strong commitment to the target of decreasing energy intensity and reducing Greenhouse gas emissions. One of the significant solutions to reach the target is increasing energy efficiency in the lighting system in the residential sector. The objective of this paper is twofold, to estimate the potency of energy saving and emission reduction from lighting in the residential sector. Literature related to the lighting system in Indonesia has been reviewed to provide sufficient data for the estimation of the energy saving and emission reduction. The results show that the in the year 2016, a total of 95.33 TWh of nationally produced electricity is used in the residential sector. This is equal to 44% of total produced electricity. The number of costumers is 64.78 million houses. The average number of lamps and average wattage of lamps used in Indonesia are 8.35 points and 13.8 W, respectively. The number of lighting and percentage of electricity used for lighting in the residential sector in Indonesia are 20.03 TWh (21.02 %) and 497 million lamps, respectively. The projection shows that in the year 2026 the total energy for lighting and number of lamps in the residential sector are 25.05 TWh and 619 million, respectively. By promoting the present technology of high efficient lamps (LED), the potency of energy saving and emission reduction in 2026 are 2.6 TWh and 2.1 million tons CO2eq, respectively.

  17. A multi-dose serological assay suitable to quantify the potency of inactivated rabies vaccines for veterinary use.

    Science.gov (United States)

    Krämer, Beate; Kamphuis, Elisabeth; Hanschmann, Kay-Martin; Milne, Catherine; Daas, Arnold; Duchow, Karin

    2013-11-01

    The mouse vaccination-challenge test, which is the most widely used method for determining the potency of inactivated rabies vaccines, is imprecise, time-consuming, and causes severe distress to the test animals. An alternative single-dose serological method has been implemented in the European Pharmacopoeia Monograph 0451 to replace the mouse challenge test for batch release. This single-dose limit method provides semi-quantitative results, but is not suitable for quantifying potency. We have now extended this serological method to a multi-dose format which allows a quantification of vaccine potency. In studies including all rabies vaccine strains relevant for Europe, we found dose-dependency for all vaccines and standard preparations. We have demonstrated that the multi-dose serological approach provides reliable quantitative potency results and is more precise than the mouse vaccination-challenge test. We have shown that adjuvanted vaccines can be calibrated against non-adjuvanted material, and that reference material can be calibrated against the International Standard. The method is therefore capable of assigning potency with the additional advantage of requiring fewer animals and reducing distress. Once the applicability of the method has been further verified in a collaborative study, it can complement the single-dose assay and eventually eliminate the need for the mouse challenge test. Copyright © 2013 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  18. Evaluation of different extraction methods on antimicrobial potency of Adenium obesum stem against food borne pathogenic bacterial strains in Oman

    Directory of Open Access Journals (Sweden)

    Mohammad Amzad Hossain

    2014-09-01

    Full Text Available Objective: To determine and compare the effect on antimicrobial potency of crude stems extract of Adenium obesum (A. obesum by Soxhlet and maceration extraction methods. Methods: The crude extracts were prepared from the coarse samples of stems with methanol by using Soxhlet and maceration extraction methods. Both the crude extracts from two extraction methods were dissolved in water and successively extracted by different polarities solvents with increasing polarities. In vitro antimicrobial potency of different polarities crude extracts obtained from Soxhlet and maceration methods was determined by agar gel diffusion method against different food borne pathogenic bacterial strains. Results: The results for antimicrobial potency of different crude extracts were almost similar by Soxhlet and maceration and methods. The average range of inhibition potency of different polarities crude extracts was 0%-17% by Soxhlet method and inhibition potency 0%-24% by maceration method. Conclusions: These results obtained from in vitro approach give promising basic information about this plant as well as some potential crude extracts can be used for the treatment of infectious diseases.

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

    Science.gov (United States)

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

    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 48h. The compounds tested showed embryotoxicity in a dose-response fashion. Functional analysis of differential gene expression after 4h 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. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Do Mesenchymal Stem Cells Derived From Atypical Lipomatous Tumors Have Greater Differentiation Potency Than Cells From Normal Adipose Tissues?

    Science.gov (United States)

    Inatani, Hiroyuki; Yamamoto, Norio; Hayashi, Katsuhiro; Kimura, Hiroaki; Takeuchi, Akihiko; Miwa, Shinji; Higuchi, Takashi; Abe, Kensaku; Taniguchi, Yuta; Yamada, Satoshi; Asai, Kiyofumi; Otsuka, Takanobu; Tsuchiya, Hiroyuki

    2017-06-01

    The p53 protein in mesenchymal stem cells (MSCs) regulates differentiation to osteogenic or adipogenic lineage. Because p53 function is depressed in most malignancies, if MSCs in malignancy also have p53 hypofunction, differentiation therapy to osteogenic or adipogenic lineage may be an effective treatment. We therefore wished to begin to explore this idea by evaluating atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) cells, because murine double minute 2 (MDM2) gene amplification, which leads to p53 hypofunction, is found in almost all ALT/WDLs. We compared osteogenic and adipogenic differentiation potency between MSCs isolated and cultured from normal adipose tissues and ALT/WDLs from the same patients. During tumor resections in six patients with ALT/WDL, we analyzed 3 mL of tumor, and for comparison, we harvested a similar amount of normal-appearing subcutaneous adipose tissue from an area remote from the tumor for comparison. Adipogenic differentiation potency was quantitatively assessed using spectrometry after oil red O staining. Osteogenic differentiation potency was semiquantitatively assessed by measuring a specific colored area after alkaline phosphatase (ALP) and alizarin red S staining. ALP is related to preosseous cellular metabolism, and alizarin red is related to calcium deposits in cell culture. There were three observers for each assessment, and each assessment (including induced-differentiation and histologic analysis) was performed in duplicate. We then analyzed the mechanism of the difference of osteogenic differentiation potency using the MDM2-specific inhibitor Nutlin-3 at various concentrations. In terms of adipogenic differentiation potency, contrary to our expectations, more fatty acid droplets were observed in MSCs derived from normal fat than in MSCs derived from ALT/WDL, although we found no significant difference between MSCs derived from ALT/WDL and MSCs derived from normal fat; the mean differentiation potency

  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. 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

  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. 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

    Full Text Available Abstract Background 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. Methods 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. Results 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

  5. 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.

  6. 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

  7. Novel natural-product-like caged xanthones with improved druglike properties and in vivo antitumor potency.

    Science.gov (United States)

    Wu, Yue; Hu, Mingyang; Yang, Li; Li, Xiang; Bian, Jinlei; Jiang, Fen; Sun, Haopeng; You, Qidong; Zhang, Xiaojin

    2015-06-15

    DDO-6101, a natural-product-like caged xanthone discovered previously in our laboratory based on the pharmacophoric scaffold of Garcinia natural product gambogic acid (GA), shows potent cytotoxicity in vitro but poor efficacy in vivo due to its poor druglike properties. In order to improve the druglike properties and in vivo cytotoxic potency, a novel series of 19 prenyl group-modified derivatives of DDO-6101 was synthesized and evaluated for their in vitro antitumor activity and druglike properties. The SAR and SPR information of these compounds was also obtained. In the light of the in vitro antitumor activity and druglike properties such as aqueous solubility and permeability, compound 6f (named as DDO-6306) was advanced into in vivo efficacy experiment. The results showed that DDO-6306 is more potent than DDO-6101 in vivo and is a promising antitumor candidate for further evaluation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Optimization of transfection conditions and analysis of siRNA potency using real-time PCR.

    Science.gov (United States)

    Cheng, Angie; Magdaleno, Susan; Vlassov, Alexander V

    2011-01-01

    RNA interference (RNAi) is a mechanism by which the introduction of small interfering RNAs (siRNAs) into cultured cells causes degradation of the complementary mRNA. Applications of RNAi include gene function analysis, pathway analysis, and target validation. While RNAi experiments have become common practice in research labs, multiple factors can influence the extent of siRNA-induced knockdown (and thus biological outcome). A properly designed and selected siRNA sequence, siRNA modification format, choice of transfection reagent/technique, optimized protocols of siRNA in vitro delivery, and an appropriate and optimized readout are all critical for ensuring a successful experiment. In this chapter, we describe a typical in vitro siRNA experiment with optimization of transfection conditions and analysis of siRNA potency, i.e., mRNA knockdown with quantitative real-time PCR.

  9. Gastropods as an evaluation tool for screening the irritating potency of absorption enhancers and drugs.

    Science.gov (United States)

    Adriaens, E; Remon, J P

    1999-08-01

    The objective of this study was to develop a simple alternative test using naked snails (slugs) for screening the irritating potency of chemicals on mucosal surfaces. The effect of various absorption enhancers and two beta-blocking agents on the mucosal tissue was determined from the total protein and lactate dehydrogenase released from the foot mucosa after treatment. Additionally, mucus production and reduction in body weight of the slugs caused by the treatment were measured. According to the effects on the mucosal epithelium of the slugs the following rank order of increasing toxicity was established: PBS, HP-beta-CD (5%), beta-CD (1.8%) and oxprenolol hydrochloride (1%) mucus production and weight loss reliable toxicity information can be obtained. This demonstrates rapid screening tests can be carried out using simple toxicity endpoints.

  10. Intelligibility in potency, intellectual potentiality and intrinsic intelligibility: Three analogical levels of perfection in Thomas Aquinas

    Directory of Open Access Journals (Sweden)

    María del Rosario Neuman

    2015-09-01

    Full Text Available ABSTRACT: One of the notions used by Saint Tomas Aquinas to refer to the corporeal being and to the spiritual being is that of «intelligible in potency» and «intelligible in act». This article delves into the meaning and scope of these concepts and in the ontological foundations of the previous distinction. The soul is considered as occupying the last place among the intelligible beings and this explains the distinction subject-object with occurs in the act of human knowledge. When considering the notion of intelligible in act an argument is found in favour of that distinction being overcome in the act of self-knowledge of a separate form. Finally, following Francisco Canals in this point, the article shows the preeminence, in the Aquinas' thoughts, of the intimacy and subsistence of the spirit above any passivity or receptivity.

  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. 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...... is to establish a mean potency, a yield estimate for professionally grown plants, and an assessment of how „professionalism” applies to domestic cultivation. We find a mean THC content in our sample normally distributed around 12% for sinsemilla (n=35) and 11.7% for resin (n=99). This is markedly higher than...... 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...

  13. Antibacterial and Antioxidant Potency of Floral Honeys from Different Botanical and Geographical Origins

    Directory of Open Access Journals (Sweden)

    Balkees A. Bakhotmah

    2012-09-01

    Full Text Available In order to assess their physicochemical and antioxidant properties as well as their antimicrobial potency, four varieties of honey from different botanical and geographical origins were used. The agar incorporation method was used to determine the antimicrobial potency of honeys. The total phenol content was determined by a modified Folin–Ciocalteu method and the free radical scavenging activity by the Fe3+ reducing power (FRAP assay. Manuka honey was the most effective against Staphylococcus aureus Oxa R and S. aureus Oxa S with a Minimum Inhibitory Concentration (MIC of 6% and 7%, respectively, whereas wild carrot honey was the most effective against Pseudomonas aeruginosa, with a MIC of 12%. Lavender honey was the least effective against all tested strains, even though was found to have the lowest pH and water content. Manuka honey had the highest content of polyphenols, with 899.09 ± 11.75 mg gallic acid/kg, whereas lavender honey had the lowest, with 111.42 ± 3.54 mg gallic acid/kg. A very significant correlation (r value was 0.9079 at P < 0.05 was observed between the total polyphenolic content and the Fe2+ content formed in the presence of the honey antioxidants. The differences between honey samples in terms of antibacterial and antioxidant activity could be attributed to the natural variations in floral sources of nectar and the different locations.

  14. 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.

  15. 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.

  16. Searching for Drug Synergy in Complex Dose-Response Landscapes Using an Interaction Potency Model.

    Science.gov (United States)

    Yadav, Bhagwan; Wennerberg, Krister; Aittokallio, Tero; Tang, Jing

    2015-01-01

    Rational design of multi-targeted drug combinations is a promising strategy to tackle the drug resistance problem for many complex disorders. A drug combination is usually classified as synergistic or antagonistic, depending on the deviation of the observed combination response from the expected effect calculated based on a reference model of non-interaction. The existing reference models were proposed originally for low-throughput drug combination experiments, which make the model assumptions often incompatible with the complex drug interaction patterns across various dose pairs that are typically observed in large-scale dose-response matrix experiments. To address these limitations, we proposed a novel reference model, named zero interaction potency (ZIP), which captures the drug interaction relationships by comparing the change in the potency of the dose-response curves between individual drugs and their combinations. We utilized a delta score to quantify the deviation from the expectation of zero interaction, and proved that a delta score value of zero implies both probabilistic independence and dose additivity. Using data from a large-scale anticancer drug combination experiment, we demonstrated empirically how the ZIP scoring approach captures the experimentally confirmed drug synergy while keeping the false positive rate at a low level. Further, rather than relying on a single parameter to assess drug interaction, we proposed the use of an interaction landscape over the full dose-response matrix to identify and quantify synergistic and antagonistic dose regions. The interaction landscape offers an increased power to differentiate between various classes of drug combinations, and may therefore provide an improved means for understanding their mechanisms of action toward clinical translation.

  17. Searching for Drug Synergy in Complex Dose–Response Landscapes Using an Interaction Potency Model

    Science.gov (United States)

    Yadav, Bhagwan; Wennerberg, Krister; Aittokallio, Tero; Tang, Jing

    2015-01-01

    Rational design of multi-targeted drug combinations is a promising strategy to tackle the drug resistance problem for many complex disorders. A drug combination is usually classified as synergistic or antagonistic, depending on the deviation of the observed combination response from the expected effect calculated based on a reference model of non-interaction. The existing reference models were proposed originally for low-throughput drug combination experiments, which make the model assumptions often incompatible with the complex drug interaction patterns across various dose pairs that are typically observed in large-scale dose–response matrix experiments. To address these limitations, we proposed a novel reference model, named zero interaction potency (ZIP), which captures the drug interaction relationships by comparing the change in the potency of the dose–response curves between individual drugs and their combinations. We utilized a delta score to quantify the deviation from the expectation of zero interaction, and proved that a delta score value of zero implies both probabilistic independence and dose additivity. Using data from a large-scale anticancer drug combination experiment, we demonstrated empirically how the ZIP scoring approach captures the experimentally confirmed drug synergy while keeping the false positive rate at a low level. Further, rather than relying on a single parameter to assess drug interaction, we proposed the use of an interaction landscape over the full dose–response matrix to identify and quantify synergistic and antagonistic dose regions. The interaction landscape offers an increased power to differentiate between various classes of drug combinations, and may therefore provide an improved means for understanding their mechanisms of action toward clinical translation. PMID:26949479

  18. 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.

  19. 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.

  20. Potency of Polycyclic Aromatic Hydrocarbons (PAHs) in chicken and Japanese quail embryos.

    Science.gov (United States)

    Franci, Cynthia D; Aleksieva, Angelika; Boulanger, Emily; Brandenburg, Jonas; Johnston, Theresa; Malinova, Asya; Head, Jessica A

    2018-01-19

    Birds are receptors of concern for polycyclic aromatic hydrocarbons (PAHs), and yet limited data describing the relative potency of PAH congeners are available for avian species. Here, we determine embryonic LD50 values for 5 PAH congeners in chicken (Gallus gallus) and one PAH congener in Japanese quail (Coturnix japonica). Graded concentrations of each test compound were injected into the air cell of chicken or quail eggs before incubation. Embryos were monitored through development (quail) or hatching (chicken). All PAHs tested caused dose-dependent increases in embryo mortality but few other effects (e.g. weight changes, deformities) were observed. In chicken, windows of developmental sensitivity were identified between embryonic days 4-9 and 20-22. The rank order potency of benzo[k]fluoranthene (76 µg/kg) ≈ dibenz[ah]anthracene (83 µg/kg) > indeno[1,2,3-cd]pyrene (325 µg/kg) > benzo[a]pyrene (461 µg/kg) > benz[a]anthracene (529 µg/kg) corresponded well with previous in vitro estimates in birds. Previously published ethoxyresorufin-O-deethylase (EROD) EC 50 values from cultured chicken embryo hepatocytes were highly predictive of our LD 50 values (p Japanese quail eggs were injected with the most potent PAH - benzo[k]fluoranthene. We found that chicken and quail were nearly equally sensitive to BkF. These results contribute to our developing understanding of variability in responses to PAHs among congeners and species. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  1. 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.

  2. 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.

  3. Sexual outcomes after organ potency-sparing surgery and glans reconstruction in patients with penile carcinoma

    Directory of Open Access Journals (Sweden)

    Gaetano Gulino

    2013-01-01

    Full Text Available Introduction: Radical surgery is the "gold standard" for treatment of invasive penile carcinoma but very poor aesthetic, functional and psychological outcomes have been reported. Our purpose was to assess the impact of organ potency-sparing surgery in locally confined carcinoma of the penis. Materials and Methods: We evaluated retrospectively 42 patients with early penile cancer (Ta,T1,T2, treated with glandulectomy and glanduloplasty with urethral mucosa and sparing of cavernosal apexes, or glandulectomy and limited apical resection in cases of Stage T2. Sexual function, ejaculation and libido were evaluated with an IIEF-15 questionnaire before the appearance of neoplasia (about three months before the surgery and six months after surgery. Quality of life was evaluated by the Bigelow-Young questionnaire. The scores relating to two weeks prior to the surgery have been compared to those obtained six months after surgery. The statistical analysis was conducted using t-Student for repeated measures and analysis of variance. Results: Six months after surgery 73% of patients reported spontaneous rigid erections, 60% coital activity while 76% of the group treated with urethral glanduloplasty reported normal ejaculation and orgasm, regained an average of 35 days after surgery. The average IIEF-15 scores reported in the entire series in the domains of erection, libido and coital activity of the pre-cancer period were not statistically different than those recorded six months after surgery. In the group treated with glandular reconstruction, pre-and postoperative IIEF-15 mean scores related to ejaculation and orgasm domains were not significantly different. Mean scores of Bigelow-Young questionnaires related to sexual pleasure, familial, social and professional relationships showed significant improvement after surgery. Conclusions: Potency sparing-sparing surgical treatments have a positive impact on a wide spectrum of the patient′s life including

  4. 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.

  5. Ultra-low-dose naltrexone reduces the rewarding potency of oxycodone and relapse vulnerability in rats.

    Science.gov (United States)

    Leri, Francesco; Burns, Lindsay H

    2005-10-01

    Ultra-low-dose opioid antagonists have been shown to enhance opioid analgesia and alleviate opioid tolerance and dependence. Our present studies in male Sprague-Dawley rats assessed the abuse potential of oxycodone+ultra-low-dose naltrexone (NTX) versus oxycodone alone. The lowest NTX dose (1 pg/kg/infusion), but not slightly higher doses (10 and 100 pg/kg/infusion), enhanced oxycodone (0.1 mg/kg/infusion) intravenous self-administration, suggesting a reduced rewarding potency per infusion. During tests of reinstatement performed in extinction conditions, co-self-administration of any of these three NTX doses significantly reduced drug-seeking precipitated by priming injections of oxycodone (0.25 mg/kg, s.c.), a drug-conditioned cue, or foot-shock stress. During self-administration on a progressive-ratio schedule, animals self-administering oxycodone (0.1 mg/kg/infusion)+NTX (1 pg/kg/infusion) reached a "break-point" sooner and showed a trend toward less responding compared to rats self-administering oxycodone alone (0.1 mg/kg/infusion). In the final experiment, the addition of ultra-low-dose NTX (10 pg/kg, s.c.) enhanced the acute stimulatory effect of oxycodone (1 mg/kg, s.c.), as well as locomotor sensitization produced by repeated oxycodone administration (7 x 1 mg/kg, s.c.). In summary, this work shows that ultra-low-dose NTX co-treatment augments the locomotor effects of oxycodone as it enhances opioid analgesia, but reduces oxycodone's rewarding potency and subsequent vulnerability to relapse.

  6. Silanol suppressing potency of alkyl-imidazolium ionic liquids on C18 stationary phases.

    Science.gov (United States)

    Fernández-Navarro, J J; Torres-Lapasió, J R; Ruiz-Ángel, M J; García-Álvarez-Coque, M C

    2012-04-06

    Residual silanols on C18 columns yield undesirable slow-kinetics ion-exchange interactions with positively charged basic compounds that result in asymmetrical peaks, low efficiencies and long retention times. The purity of the silica employed as supporting material, and the technique used to form the bonded phase, which varies with the brand and manufacturer, give rise to different amounts of residual silanols in the packings, and consequently, different chromatographic performance. One of the most efficient and widespread strategies to reduce or even eliminate the different performance among columns is the addition of a reagent to the mobile phase to block the silanol sites. However, the intrinsic nature of both stationary phase and additive leads to particular results. In this work, a group of basic compounds were analysed using six C18 stationary phases (Zorbax SB-C18, X-Terra MS C18, Kromasil, Lichrospher, Nucleosil, and Spherisorb) and acetonitrile-water mixtures. Two ionic liquids (ILs), 1-butyl- and 1-hexyl-3-methyl-imidazolium tetrafluoroborates, were added to the mobile phases to evaluate their silanol suppressing potency, based on the decreased retention of the basic compounds when the silanols are blocked (described by the Horváth equation), and the improvement in peak profile (described by the plots of the peak half-widths at diverse retention times). The suppressing potency based on the retention can be misleading when the adsorption of the IL anion is not negligible, since the anion attracts the cationic basic compounds increasing the retention. However, the accessibility of basic compounds to the silanols is prevented by both IL cation and anion, improving the peak profiles for all stationary phases. This was especially remarkable for Spherisorb, which in the absence of additive yielded by far the worst performance. 1-Hexyl-3-methyl-imidazolium tetrafluoroborate was the best additive in terms of retention and peak profile (width and asymmetry

  7. 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

  8. Determination of in vitro relative potency (REP) values for mono-ortho polychlorinated biphenyls after purification with active charcoal

    NARCIS (Netherlands)

    Peters, A.K.; Leonards, P.E.G.; Zhao, B.; Bergman, A.; Denison, M.S.; Berg, van den M.

    2006-01-01

    The TEF system for dioxin-like compounds has included assignment of TEF values for mono-ortho polychlorinated biphenyls (MO-PCBs). Small traces of aryl hydrocarbon receptor (AhR)-active impurities could result in artifactually higher relative potency (REP) values. MO-PCBs -105, -118, -156, and -167

  9. 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...

  10. Principles for identification of High Potency Category Chemicals for which the Dermal Sensitisation Threshold (DST) approach should not be applied.

    Science.gov (United States)

    Roberts, David W; Api, Anne Marie; Safford, Robert J; Lalko, Jon F

    2015-08-01

    An essential step in ensuring the toxicological safety of chemicals used in consumer products is the evaluation of their skin sensitising potential. The sensitising potency, coupled with information on exposure levels, can be used in a Quantitative Risk Assessment (QRA) to determine an acceptable level of a given chemical in a given product. Where consumer skin exposure is low, a risk assessment can be conducted using the Dermal Sensitisation Threshold (DST) approach, avoiding the need to determine potency experimentally. Since skin sensitisation involves chemical reaction with skin proteins, the first step in the DST approach is to assess, on the basis of the chemical structure, whether the chemical is expected to be reactive or not. Our accompanying publication describes the probabilistic derivation of a DST of 64 μg/cm(2) for chemicals assessed as reactive. This would protect against 95% of chemicals assessed as reactive, but the remaining 5% would include chemicals with very high potency. Here we discuss the chemical properties and structural features of high potency sensitisers, and derive an approach whereby they can be identified and consequently excluded from application of the DST. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Post-synthetic modification of human alpha-fetoprotein revealed by isoelectric focusing controls its immunosuppressive potency

    Energy Technology Data Exchange (ETDEWEB)

    Lester, E. P.; Miller, J. B.; Yachnin, S.

    1977-01-01

    We have demonstrated 3 variants of human alpha-fetoprotein (HAFP) by crossed immunoelectrophoresis, and have correlated the capacity of HAFP isolates to suppress human lymphocyte transformation in vitro with the relative proportion of the electronegative variant, HAFP-3, present in each isolate. We have now isolated HAFP from the serum, ascitic fluid, and saline extract of tumor from a single hepatoma patient, and from an homogenate of fetal livers. When tested for their capacity to inhibit human lymphocyte transformation in vitro, tumor and fetal liver HAFP were found to be extremely potent; serum HAFP had intermediate potency, and ascitic fluid HAFP was the least potent. Analysis of these HAFP isolates by crossed immunoelectrophoresis confirmed the correlation between the proportion of HAFP-3 and the immunosuppressive potency of each isolate. In addition, analysis of these HAFP isolates by isoelectric focusing in polyacrylamide gels containing 8 M urea revealed further evidence of microheterogeneity; at least 6 molecular variants were apparent. The proportion of one of these variants, termed HAFP-3a, in each isolate was correlated with the immunosuppressive potency of the isolate. The sialic acid content of the various HAFP isolates did not vary significantly. Our data suggest that a post-synthetic modification of HAFP occurs, which modulates its immunosuppressive potency.

  12. 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

  13. 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.

  14. Avian influenza in ovo vaccination with replication defective recombinant adenovirus in chickens: Vaccine potency, antibody persistence, and maternal antibody transfer

    Science.gov (United States)

    Protective immunity against avian influenza (AI) can be elicited in chickens in a single-dose regimen by in ovo vaccination with a replication-competent adenovirus (RCA)-free human adenovirus serotype 5 (Ad)-vector encoding the AI virus (AIV) hemagglutinin (HA). We evaluated vaccine potency, antibo...

  15. 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

    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...

  16. Prediction of cyclin-dependent kinase 2 inhibitor potency using the fragment molecular orbital method

    Directory of Open Access Journals (Sweden)

    Mazanetz Michael P

    2011-01-01

    Full Text Available Abstract Background The reliable and robust estimation of ligand binding affinity continues to be a challenge in drug design. Many current methods rely on molecular mechanics (MM calculations which do not fully explain complex molecular interactions. Full quantum mechanical (QM computation of the electronic state of protein-ligand complexes has recently become possible by the latest advances in the development of linear-scaling QM methods such as the ab initio fragment molecular orbital (FMO method. This approximate molecular orbital method is sufficiently fast that it can be incorporated into the development cycle during structure-based drug design for the reliable estimation of ligand binding affinity. Additionally, the FMO method can be combined with approximations for entropy and solvation to make it applicable for binding affinity prediction for a broad range of target and chemotypes. Results We applied this method to examine the binding affinity for a series of published cyclin-dependent kinase 2 (CDK2 inhibitors. We calculated the binding affinity for 28 CDK2 inhibitors using the ab initio FMO method based on a number of X-ray crystal structures. The sum of the pair interaction energies (PIE was calculated and used to explain the gas-phase enthalpic contribution to binding. The correlation of the ligand potencies to the protein-ligand interaction energies gained from FMO was examined and was seen to give a good correlation which outperformed three MM force field based scoring functions used to appoximate the free energy of binding. Although the FMO calculation allows for the enthalpic component of binding interactions to be understood at the quantum level, as it is an in vacuo single point calculation, the entropic component and solvation terms are neglected. For this reason a more accurate and predictive estimate for binding free energy was desired. Therefore, additional terms used to describe the protein-ligand interactions were then

  17. Potency of Palm Oil Plantation and Mill Byproduct as Ruminant Feed in Paser Regency, East Kalimantan

    Directory of Open Access Journals (Sweden)

    Hamdi Mayulu

    2013-10-01

    Full Text Available By-product produced from plantation and palm oil mill can be utilized for energy and protein source of ruminant feed. Thus, it still has potency for further exploration. The objective of the research was to investigate the nutrient value of palm oil plantation and mill’s by-product used to formulate ruminant feed. The research located in 66,118.5 ha of palm oil plantation in Paser regency, East Kalimantan province. The research was carried out in palm oil plantation and mill of PTPN XIII comprising productive plants (TM in +14,000 ha arranged in 9 divisions (afdeling. Measured variables consisted of: 1 dry mass production (mass of midrib every cutting and frond (kg;                        2 Centrosema sp mass production (kg; 3 mass of empty fruit bunches (kg; palm pressed fiber (PPF (kg, palm kernel cake (PKC (kg dan palm oil sludge (POS (kg; 4 nutrient content analyzed under proximate analysis in accordance with the procedure of Ruminant Feed Nutrient Laboratory, Faculty of Livestock, Diponegoro University. The result showed that total dry matter (DM production was 14.82 ton/ha/year, consisting: midrib 29.09% (crude protein (CP 3.16% and crude fiber (CF 37.85%, frond 10.31% (CP 6.53% dan CF 30.39%, Centrosema sp. 2.48% (CP 22.58% and CF 35.12, EFB 24.31% (CP 7.01% and CF 40.22%, PPF 1.23% (CP 5.56% and CF 50.36%, PKC 1.29% (CP 15.49% and CF10.45 and POS 1.20% (CP 17.86% and CF 45.99%. This could be concluded that palm oil plantation and mill’s by-product was recommended for ruminant feed as it had huge amount and appropriate nutrient contentDoi: 10.12777/ijse.5.2.56-60 [How to cite this article: Mayulu, H., Sunarso, C. I. Sutrisno, Sumarsono, M. Christiyanto, K. Isharyudono. (2013.  Potency of Palm Oil Plantation and Mill Byproduct as Ruminant Feed in Paser Regency, East Kalimantan, 5(2,56-60. Doi: 10.12777/ijse.5.2.56-60

  18. Alternative splicing in nicotinic acetylcholine receptor subunits from Locusta migratoria and its influence on acetylcholine potencies.

    Science.gov (United States)

    Zhang, Yixi; Liu, Yang; Bao, Haibo; Sun, Huahua; Liu, Zewen

    2017-01-18

    Due to the great abundance within insect central nervous system (CNS), nicotinic acetylcholine receptors (nAChRs) play key roles in insect CNS, which makes it to be the targets of several classes of insecticides, such as neonicotinoids. Insect nAChRs are pentameric complexes consisting of five subunits, and a dozen subunits in one insect species can theoretically comprise diverse nAChRs. The alternative splicing in insect nAChR subunits may increase the diversity of insect nAChRs. In the oriental migratory locust (Locusta migratoria manilensis Meyen), a model insect species with agricultural importance, the alternative splicing was found in six α subunits among nine α and two β subunits, such as missing conserved residues in Loop D from Locα1, Locα6 and Locα9, a 34-residue insertion in Locα8 cytoplasmic loop, and truncated transcripts for Locα4, Locα7 and Locα9. Hybrid nAChRs were successfully constructed in Xenopus oocytes through co-expression with rat β2 and one α subunit from L. migratoria, which included Locα1, Locα2, Locα3, Locα4, Locα5, Locα8 and Locα9. Influences of alternative splicing in Locα1, Locα8 and Locα9 on acetylcholine potency were tested on hybrid nAChRs. The alternative splicing in Locα1 and Locα9 could increase acetylcholine sensitivities on recombinant receptors, while the splicing in Locα8 showed significant influences on the current amplitudes of oocytes. The results revealed that the alternative splicing at or close to the ligand-binding sites, as well as at cytoplasmic regions away from the ligand-binding sites, in insect nAChR subunits would change the agonist potencies on the receptors, which consequently increased nAChR diversity in functional and pharmacological properties. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Novel Fusion Protein Targeting Mitochondrial DNA Improves Pancreatic Islet Functional Potency and Islet Transplantation Outcomes.

    Science.gov (United States)

    Danobeitia, Juan S; Chlebeck, Peter J; Shokolenko, Inna; Ma, Xiaobo; Wilson, Glenn; Fernandez, Luis A

    2017-11-01

    Long-term graft survival is an ongoing challenge in the field of islet transplantation. With the growing demand for transplantable organs, therapies to improve organ quality and reduce the incidence of graft dysfunction are of paramount importance. We evaluated the protective role of a recombinant DNA repair protein targeted to mitochondria (Exscien I-III), as a therapeutic agent using a rodent model of pancreatic islet transplantation. We first investigated the effect of therapy on isolated rat islets cultured with pro-inflammatory cytokines (interleukin-1 β, interferon γ, and tumor necrosis factor α) for 48 h and documented a significant reduction in apoptosis by flow cytometry, improved viability by immunofluorescence, and conserved functional potency in vitro and in vivo in Exscien I-III-treated islets. We then tested the effect of therapy in systemic inflammation using a rat model of donor brain death (BD) sustained for a 6-h period. Donor rats were allocated to 4 groups: (non-BD + vehicle, non-BD + Exscien I-III, BD + vehicle, and BD + Exscien I-III) and treated with Exscien I-III (4 mg/kg) or vehicle 30 min after BD induction. Sham (non-BD)-operated animals receiving either Exscien I-III or vehicle served as controls. Islets purified from BD + Exscien I-III-treated donors showed a significant increase in glucose-stimulated insulin release in vitro when compared to islets from vehicle-treated counterparts. In addition, donor treatment with Exscien I-III attenuated the effects of BD and significantly improved the functional potency of transplanted islets in vivo. Our data indicate that mitochondrially targeted antioxidant therapy is a novel strategy to protect pancreas and islet quality from the deleterious effects of cytokines in culture and during the inflammatory response associated with donation after BD. The potential for rapid translation into clinical practice makes Exscien I-III an attractive therapeutic option for the management of brain

  20. The potency of plant extracts as antimicrobials for the skin or hide preservation

    Science.gov (United States)

    Suparno, Ono; Afifah, Amalia; Panandita, Tania; Marimin, Purnawati, Rini

    2017-03-01

    and antimicrobial potency compared to the extracts of moringa, cucumber tree starfruit, and cherry leaves. Therefore, the ethanol extract of white leadtree leaf had a potency as a preservative of animal skin or hide and might be able to substitute the biocides used in the skin or hide preservation.

  1. La terapia láser de baja potencia en la medicina cubana Low potency laser therapy in Cuban medicine

    Directory of Open Access Journals (Sweden)

    Adel Hernández Díaz

    2008-06-01

    Full Text Available El surgimiento y desarrollo del láser fue posible gracias a los avances previamente logrados en otras disciplinas científicas en el pasado siglo. Desde el punto de vista práctico puede ser considerado como un haz estrecho de luz monocromática y coherente que puede encontrarse en el rango visible, infrarrojo o ultravioleta del espectro de las radiaciones electromagnéticas. Motivados por la incorporación de los equipos láser de producción nacional en las salas de rehabilitación de los policlínicos universitarios de la atención primaria y otros centros de salud del país, nos dimos a la tarea de realizar este trabajo, cuyo objetivo fundamental es presentar las distintas aplicaciones del láser de baja potencia en la medicina, y los equipos láser cubanos disponibles en la red nacional de salud pública. Además se muestran los efectos terapéuticos de la radiación láser y los mecanismos internos para lograrlos, y se detallan ampliamente las contraindicaciones de la terapia. Este tipo de tratamiento ofrece muchas posibilidades de ayuda terapéutica y permite ser utilizado con éxito en patologías de diversas especialidades. La terapia láser constituye un tratamiento de primera línea para muchas de las afecciones con que acuden los pacientes a consulta médica.The appearance and development of laser was possible thanks to the advances previously attained in other scientific disciplines in the last century. From the practical point of view, it may be considered as a narrow monochromatic and coherent beam of light that may be found in the visible infrared or ultraviolet range of the spectrum of electromagnetic radiations. Motivated by the introduction of the laser equipment of national production into the rehabilitation wards of the teaching polyclinics and other health centres of the country, we made this paper aimed at presenting the different applications of low potency laser in the medical sphere, as well as the Cuban laser

  2. Immunomodulatory Potency of Microcystin, an Important Water-Polluting Cyanobacterial Toxin.

    Science.gov (United States)

    Adamovsky, Ondrej; Moosova, Zdena; Pekarova, Michaela; Basu, Amrita; Babica, Pavel; Svihalkova Sindlerova, Lenka; Kubala, Lukas; Blaha, Ludek

    2015-10-20

    Microcystins (MCs) are primarily hepatotoxins produced by cyanobacteria and are responsible for intoxication in humans and animals. There are many incidents of chronic exposure to MCs, which have been attributed to the inappropriate treatment of water supplies or contaminated food. Using RAW 264.7 macrophages, we showed the potency of microcystin-LR (MC-LR) to stimulate production of pro-inflammatory cytokines (tumor necrosis factor α and interleukin-6) as a consequence of fast nuclear factor κB and nitrogen-activated protein kinase activation. In contrast to other studies, the observed effects were not attributed to the intracellular inhibition of protein phosphatases 1/2A due to lack of specific transmembrane transporters for MCs. However, the MC-LR-induced activation of macrophages was effectively inhibited by a specific peptide that blocks signaling of receptors, which play a pivotal role in the innate immune responses. Taken together, we showed for the first time that MC-LR could interfere with macrophage receptors that are responsible for triggering the above-mentioned signaling pathways. These findings provide an interesting mechanistic explanation of some adverse health outcomes associated with toxic cyanobacteria and MCs.

  3. 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.

  4. 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.

  5. 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.

  6. Operating a motor vehicle after marijuana use: Perspectives from people who use high-potency marijuana.

    Science.gov (United States)

    Cavazos-Rehg, Patricia A; Krauss, Melissa J; Sowles, Shaina J; Zewdie, Kidist; Bierut, Laura

    2018-01-02

    With advancing marijuana legalization in the United States, a primary concern is the possible increase in consequences relating to marijuana driving impairment, especially among people who use high-potency marijuana (i.e., extracts). In this study, the research team assessed the risk perception and experiences of driving under the influence of marijuana by investigating people who use extracts. Participants from 2 studies were queried about driving after using marijuana. In Study 1, phone interviews (n = 19) were conducted with people who use extracts. In Study 2, people who use extracts (n = 174) were recruited to participate in a nationwide survey via an online existing panel. Responses to marijuana and driving-related questions were qualitatively coded for themes (e.g., riskiness, engagement in behavior) developed by the research team. Prominent themes identified in Study 1 suggested a belief that driving risk following marijuana use is dependent on the individual (i.e., response/tolerance) or the amount/type of marijuana consumed. This theme was corroborated by Study 2 participants. Those who perceived no or minimal risk from driving following marijuana use were more likely to report engagement in driving following extracts use. More research is needed to understand how marijuana, especially in its concentrated form, impacts driving ability in order to develop appropriate and scientifically sound regulations. Such research could subsequently fill the need to improve and more widely disseminate prevention messages on marijuana use and driving risks.

  7. Estimation of cytotoxic potency by brine shrimp lethality bioassay application of Clerodendrum infortunatum Linn.

    Directory of Open Access Journals (Sweden)

    Talukdar Muhammad Waliullah

    2015-08-01

    Full Text Available Objective: To learn a scientific and systematic knowledge of anticancer, antimicrobial and pharmacological activities of natural products and estimate cytotoxic potency by using ethanol and chloroform extracts of root, leaf and stem of Clerodendrum infortunatum (Verbenaceae due to its random use in customary and traditional medicine to cure common ailments such as intestinal disorder, diarrhea, tuberculosis and respiratory problems etc. Methods: The in vitro application was carried out with the bench-top bioassay method by using brine shrimp lethality bioassay. Results: All of the crude extracts were found to be lethal and effective. The LC50 value of ethyl alcohol fraction of root was 20.845 mg/L compared to the standard drug tetracycline of 14.675 mg/L to brine shrimp nauplii, indicating that the extracts were biologically active. Conclusions: The cytotoxic study of LC50 value showed that a good correlation with the antibiotic tetracycline. From the comparative correlation error bars and percentage, we understood that ethyl alcohol fraction of root extract was very effective. This study serves as a basis for further research to lead compounds to be isolated so that it may be as a template for the implications of these results for bioactivity and drug discovery potential of herbal products.

  8. The impact of gallium content on degradation, bioactivity, and antibacterial potency of zinc borate bioactive glass.

    Science.gov (United States)

    Rahimnejad Yazdi, Alireza; Torkan, Lawrence; Stone, Wendy; Towler, Mark R

    2018-01-01

    Zinc borate glasses with increasing gallium content (0, 2.5, 5, 10, and 15 Wt % Ga) were synthesized and their degradation, bioactivity in simulated body fluid (SBF), and antibacterial properties were investigated. ICP measurements showed that increased gallium content in the glass resulted in increased gallium ion release and decreased release of other ions. Degradability declined with the addition of gallium, indicating the formation of more symmetric BO 3 units with three bridging oxygens and asymmetric BO 3 units with two bridging oxygens in the glass network as the gallium content in the series increased. The formation of amorphous CaP on the glass surface after 24 h of incubation in SBF was confirmed by SEM, XRD, and FTIR analyses. Finally, antibacterial evaluation of the glasses using the agar disc-diffusion method demonstrated that the addition of gallium increased the antibacterial potency of the glasses against P. aeruginosa (Gram-negative) while decreasing it against S. epidermidis (Gram-positive); considering the ion release trends, this indicates that the gallium ion is responsible for the glasses' antibacterial behavior against P. aeruginosa while the zinc ion controls the antibacterial activity against S. epidermidis. The statistical significance of the observed trends in the measurements were confirmed by applying the Kruskal-Wallis H Test. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 367-376, 2018. © 2017 Wiley Periodicals, Inc.

  9. 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.

  10. 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.

  11. 3,4',5-trans-Trimethoxystilbene; a natural analogue of resveratrol with enhanced anticancer potency.

    Science.gov (United States)

    Aldawsari, Fahad S; Velázquez-Martínez, Carlos A

    2015-06-01

    Resveratrol is a phytoalexin produced by many plant species as a defence mechanism. Over the last decade, this polyphenol has been reported to be active against multiple targets associated with chronic disorders. However, its poor pharmacokinetic profile, as well as multiple discrepancies related to its in vitro and in vivo profile, has resulted not only on the study of suitable delivery systems, but the use of resveratrol derivatives. In this regard, the 3,4',5-trans-trimethoxystilbene (TMS), a natural analogue of resveratrol, has emerged as a strong candidate. TMS has an enhanced anticancer profile compared to resveratrol, exhibiting higher potency than resveratrol, as shown by multiple reports describing an improved cancer cell proliferation inhibition, induction of cell cycle arrest, decreased metastasis, reduced angiogenesis, and increased apoptosis. In this review, we provide a concise summary of results reported in the literature, related to the similarities and differences between resveratrol and TMS, and we submit to the scientific community that TMS is a promising and (still) understudied natural agent candidate, with potential applications in cancer research. Nevertheless, based on the available evidence, we also submit to the scientific community that TMS may also find a niche in any other research area in which resveratrol has been used.

  12. A Web Server and Mobile App for Computing Hemolytic Potency of Peptides

    Science.gov (United States)

    Chaudhary, Kumardeep; Kumar, Ritesh; Singh, Sandeep; Tuknait, Abhishek; Gautam, Ankur; Mathur, Deepika; Anand, Priya; Varshney, Grish C.; Raghava, Gajendra P. S.

    2016-03-01

    Numerous therapeutic peptides do not enter the clinical trials just because of their high hemolytic activity. Recently, we developed a database, Hemolytik, for maintaining experimentally validated hemolytic and non-hemolytic peptides. The present study describes a web server and mobile app developed for predicting, and screening of peptides having hemolytic potency. Firstly, we generated a dataset HemoPI-1 that contains 552 hemolytic peptides extracted from Hemolytik database and 552 random non-hemolytic peptides (from Swiss-Prot). The sequence analysis of these peptides revealed that certain residues (e.g., L, K, F, W) and motifs (e.g., “FKK”, “LKL”, “KKLL”, “KWK”, “VLK”, “CYCR”, “CRR”, “RFC”, “RRR”, “LKKL”) are more abundant in hemolytic peptides. Therefore, we developed models for discriminating hemolytic and non-hemolytic peptides using various machine learning techniques and achieved more than 95% accuracy. We also developed models for discriminating peptides having high and low hemolytic potential on different datasets called HemoPI-2 and HemoPI-3. In order to serve the scientific community, we developed a web server, mobile app and JAVA-based standalone software (http://crdd.osdd.net/raghava/hemopi/).

  13. Evaluation of a digital dispenser for direct curve dilutions in a vaccine potency assay.

    Science.gov (United States)

    Roselle, Christopher; Whitehouse, Dana; Follmer, Thy; Ansbro, Fran; Bouaraphan, Silikhone; Guan, Liming; Wang, Sha-Ke; Shank-Retzlaff, Mary; Verch, Thorsten

    2017-03-01

    Dilutions are a common source of analytical error, both in terms of accuracy and precision, and a common source of analyst mistakes. When serial dilutions are used, errors compound, even when employing laboratory automation. Direct point dilutions instead of serial dilutions can reduce error but is often impractical as they require either large diluent volumes or very small sample volumes when performed with traditional liquid handling equipment. We evaluated preparation of dilution curves using a picoliter digital dispenser, the HP, Inc. / TECAN D300 which is capable of accurately delivering picoliter volumes directly into sample wells filled with assay diluent. Dilution linearity and variability of the direct dilutions were similar to or less than those generated with a traditional liquid handler as measured using a fluorophore assay and an ELISA used to measure vaccine potency. Minimum concentrations for detergent in the dispensed sample were identified but no correlation with detergent characteristics was observed. The tolerance to protein in the sample was evaluated as well with up to 5% BSA having no impact on dispense linearity and precision. We found the digital dispenser to reduce automation complexity while maintaining or improving assay performance in addition to facilitating complex plate lay-outs. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. 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.

  15. A new carbohydrate-based wound dressing fibre with superior absorption and antimicrobial potency.

    Science.gov (United States)

    Miraftab, M; Masood, R; Edward-Jones, V

    2014-01-30

    Heavily exudating wounds can lead to infection and unnecessary trauma if they are not adequately managed. Manufacturers involved in production and marketing of high absorption silver dressings, besides emphasising high absorptions of their dressings are keen to highlight potent antimicrobial abilities of their products against all kinds of pathogens including MRSA. However, there are little or no credible reports on minimal but potent quantities of silver needed in a dressing to eliminate bacteria spread and growth or how effectively the silver within a dressing is released over time. This paper introduces a new hybrid biomaterial fibre made from polysaccharide-based polymers with inbuilt ability to gel and absorb large quantities of pseudo exudates. Furthermore, it will be reported that the new fibre carries up to six times less silver than it is conventionally used in silver dressings and displays a very slow rate of release whilst maintaining full potency over time against known Gram positive, Gram negative micro-organisms including MRSA. The paper concludes that the developed hybrid fibre has long lasting antimicrobial and gelling properties comparable, if not better, than Acticoat AA and Aquacel Ag, two commercially available silver dressings. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Estimation of Maximum Recommended Therapeutic Dose Using Predicted Promiscuity and Potency.

    Science.gov (United States)

    Liu, T; Oprea, T; Ursu, O; Hasselgren, C; Altman, R B

    2016-12-01

    We report a simple model that predicts the maximum recommended therapeutic dose (MRTD) of small molecule drugs based on an assessment of likely protein-drug interactions. Previously, we reported methods for computational estimation of drug promiscuity and potency. We used these concepts to build a linear model derived from 238 small molecular drugs to predict MRTD. We applied this model successfully to predict MRTDs for 16 nonsteroidal antiinflammatory drugs (NSAIDs) and 14 antiretroviral drugs. Of note, based on the estimated promiscuity of low-dose drugs (and active chemicals), we identified 83 proteins as "high-risk off-targets" (HROTs) that are often associated with low doses; the evaluation of interactions with HROTs may be useful during early phases of drug discovery. Our model helps explain the MRTD for drugs with severe adverse reactions caused by interactions with HROTs. © 2016 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  17. 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.

  18. α-Methylation enhances the potency of isoprenoid triazole bisphosphonates as geranylgeranyl diphosphate synthase inhibitors.

    Science.gov (United States)

    Matthiesen, Robert A; Varney, Michelle L; Xu, Pauline C; Rier, Alex S; Wiemer, David F; Holstein, Sarah A

    2018-01-15

    Disruption of protein geranylgeranylation via inhibition of geranylgeranyl diphosphate synthase (GGDPS) represents a novel therapeutic strategy for a variety of malignancies, especially those characterized by excessive protein secretion such as multiple myeloma. Our work has demonstrated that some isoprenoid triazole bisphosphonates are potent and selective inhibitors of GGDPS. Here we present the synthesis and biological evaluation of a new series of isoprenoid triazoles modified by incorporation of a methyl group at the α-carbon. These studies reveal that incorporation of an α-methyl substituent enhances the potency of these compounds as GGDPS inhibitors, and, in the case of the homogeranyl/homoneryl series, abrogates the effects of olefin stereochemistry on inhibitory activity. The incorporation of the methyl group allowed preparation of a POM-prodrug, which displayed a 10-fold increase in cellular activity compared to the corresponding salt. These studies form the basis for future preclinical studies investigating the anti-myeloma activity of these novel α-methyl triazole bisphosphonates. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. 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.

  20. 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.

  1. 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.

  2. Antibacterial potency of housefly larvae extract from sewage sludge through bioconversion.

    Science.gov (United States)

    Zheng, Chaocheng; Zhou, Lixiang

    2013-09-01

    Use of the fly to convert sewage sludge into nutrient-rich soil conditioner and amendment is an attractive approach for sludge bioconversion. During this process, fecal coliforms, an indicating pathogen, in sludge were reduced to 5.3 x 10(2) most probable number/g dry solid from initial 3.32 x 10(6) MPN/g dry solid. It was also found that the extract of larvae grown in sludge during bioconversion have an observable inhibitory effect against bacteria compared to larvae grown in wheat bran as measured by minimum bacterial concentration tests. In vitro antimicrobial assay tests over time also showed that the extract had strong inhibitory efficiencies of ca. 99% against Bacillus cereus, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Serratia marcescens, while the efficiency was 69% and 57% against Bacillus subtilis and Klebsiella pneumoniae, respectively. The observed pathogenic bacterial cell membrane damage was found to be responsible for the phenomenon mentioned above, with nuclear acids leaching out quickly and alkaline phosphatase increasing in the outer membrane, followed by an increase of beta-galactosidase in the inner membrane. Clearly, housefly larvae extract from sewage sludge through bioconversion possesses antibacterial potency against pathogenic bacteria.

  3. Replacing the NIH test for rabies vaccine potency testing: a synopsis of drivers and barriers.

    Science.gov (United States)

    Schiffelers, Marie-Jeanne; Blaauboer, Bas; Bakker, Wieger; Hendriksen, Coenraad

    2014-07-01

    Approximately 70% of animal use is utilized to demonstrate quality control of vaccines. Especially rabies vaccine potency testing, using the NIH challenge test, involves objections in terms of scientific relevance, animal welfare concern and costs. Several 3R models have been proposed to refine, reduce or replace this test. Some are formally incorporated into regulatory requirements, but actual regulatory acceptance and use by industry lags behind, raising the question concerning which factors influence this process. This question is answered by a combination of literature review, interviews and a survey among 50 rabies vaccine experts. The findings are analyzed using the multilevel perspective on technology transition, which distinguishes 3 levels of factors influencing innovation acceptance. At the micro level (where 3R models are developed and validated) the dis-advantages of, and fractional experience with, 3R models, scarce data sharing and demanding validation processes exist. The meso level (existing regulatory regime) encloses the barriers of the 'gold standard', the lack of harmonization and the driving force of legislation stimulating 3Rs use. The macro level (the societal context) combines risk aversion and increased concern for animal welfare. Regulatory acceptance and use of 3R models requires dedicated stakeholder communication, cooperation and coordination at all three levels. Copyright © 2014 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  4. 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

  5. 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

  6. 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

  7. 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.

  8. A Web Server and Mobile App for Computing Hemolytic Potency of Peptides.

    Science.gov (United States)

    Chaudhary, Kumardeep; Kumar, Ritesh; Singh, Sandeep; Tuknait, Abhishek; Gautam, Ankur; Mathur, Deepika; Anand, Priya; Varshney, Grish C; Raghava, Gajendra P S

    2016-03-08

    Numerous therapeutic peptides do not enter the clinical trials just because of their high hemolytic activity. Recently, we developed a database, Hemolytik, for maintaining experimentally validated hemolytic and non-hemolytic peptides. The present study describes a web server and mobile app developed for predicting, and screening of peptides having hemolytic potency. Firstly, we generated a dataset HemoPI-1 that contains 552 hemolytic peptides extracted from Hemolytik database and 552 random non-hemolytic peptides (from Swiss-Prot). The sequence analysis of these peptides revealed that certain residues (e.g., L, K, F, W) and motifs (e.g., "FKK", "LKL", "KKLL", "KWK", "VLK", "CYCR", "CRR", "RFC", "RRR", "LKKL") are more abundant in hemolytic peptides. Therefore, we developed models for discriminating hemolytic and non-hemolytic peptides using various machine learning techniques and achieved more than 95% accuracy. We also developed models for discriminating peptides having high and low hemolytic potential on different datasets called HemoPI-2 and HemoPI-3. In order to serve the scientific community, we developed a web server, mobile app and JAVA-based standalone software (http://crdd.osdd.net/raghava/hemopi/).

  9. Ultra-low doses of naltrexone or etorphine increase morphine's antinociceptive potency and attenuate tolerance/dependence in mice.

    Science.gov (United States)

    Shen, K F; Crain, S M

    1997-05-23

    In previous studies we showed that low (pM) concentrations of naloxone (NLX), naltrexone (NTX) or etorphine selectively antagonize excitatory, but not inhibitory, opioid receptor-mediated functions in nociceptive types of sensory neurons in culture. Cotreatment of these neurons with pM NTX or etorphine not only results in marked enhancement of the inhibitory potency of acutely applied nM morphine [or other bimodally-acting (inhibitory/excitatory) opioid agonists], but also prevents development of cellular manifestations of tolerance and dependence during chronic exposure to microM morphine. These in vitro studies were confirmed in vivo by demonstrating that acute cotreatment of mice with morphine plus a remarkably low dose of NTX (ca. 10 ng/kg) does, in fact, enhance the antinociceptive potency of morphine, as measured by hot-water tail-flick assays. Furthermore, chronic cotreatment of mice with morphine plus low doses of NTX markedly attenuates development of naloxone-precipitated withdrawal-jumping in physical dependence assays. The present study provides systematic dose-response analyses indicating that NTX elicited optimal enhancement of morphine's antinociceptive potency in mice when co-administered (i.p.) at about 100 ng/kg together with morphine (3 mg/kg). Doses of NTX as low as 1 ng/kg or as high as 1 microg/kg were still effective, but to a lesser degree. Oral administration of NTX in the drinking water of mice was equally effective as i.p. injections in enhancing the antinociceptive potency of acute morphine injections and even more effective in attenuating development of tolerance and NLX-precipitated withdrawal-jumping during chronic cotreatment. Cotreatment with a subanalgesic dose of etorphine (10 ng/kg) was equally effective as NTX in enhancing morphine's antinociceptive potency and attenuating withdrawal-jumping after chronic exposure. These studies provide a rationale for the clinical use of ultra-low-dose NTX or etorphine so as to increase the

  10. Report on the international workshop on alternative methods for Leptospira vaccine potency testing: state of the science and the way forward.

    Science.gov (United States)

    Stokes, William; Srinivas, Geetha; McFarland, Richard; Kulpa-Eddy, Jodie; Casey, Warren; Walker, Angela; Draayer, Hans; Sebring, Randy; Brown, Karen; Balks, Elisabeth; Stirling, Catrina; Klaasen, Eric; Hill, Richard; Rippke, Byron; Ruby, Kevin; Alt, David; Mukhopadhyay, Suman; Kojima, Hajime; Johnson, Nelson; Rinckel, Lori; Doelling, Vivian; Jones, Brett

    2013-09-01

    Routine potency testing of Leptospira vaccines is mostly conducted using a vaccination-challenge test that involves large numbers of hamsters and unrelieved pain and distress. NICEATM, ICCVAM, and their international partners organized a workshop to review the state of the science of alternative methods that might replace, reduce, and refine the use of animals for veterinary Leptospira vaccine potency testing and to identify ways to advance improved alternative methods. Vaccine manufacturers were encouraged to initiate or continue product-specific validation using in vitro enzyme-linked immunosorbent assays as replacements for potency testing of four common Leptospira serogroups. Participants discussed the potential for eliminating the back-titration procedure in the hamster challenge assay, which could reduce animal use by 50% for each individual potency test. Further animal reduction may also be possible by using cryopreserved Leptospira stock to replace continual passaging through hamsters. Serology assays were identified as a way to further reduce and refine animal use but should be considered only after attempting in vitro assays. Workshop participants encouraged consideration of analgesics and use of earlier humane endpoints when the hamster vaccination-challenge potency assay is used. International harmonization of alternative potency methods was recommended to avoid duplicative potency testing to meet regionally different requirements. Copyright © 2013. Published by Elsevier Ltd.. All rights reserved.

  11. Affective Urbanism

    DEFF Research Database (Denmark)

    Samson, Kristine

    Urban design and architecture are increasingly used as material and affective strategies for setting the scene, for manipulation and the production of urban life: The orchestration of atmospheres, the framing and staging of urban actions, the programming for contemplation, involvement, play......, experience and consumption are all strategic design tools applied by planners and architects. Whereas urban design in former modernist planning served merely functional or political means, urban design has increasingly become an aesthetical mediator of ideologies embedded in the urban field of life forces....... Under these circumstances affective aesthetics operate strategically within the urban field of interests, capital flows and desires of the social. This ‘affective urbanism’ (Anderson & Holden 2008) is linked to a society influenced by new kinds of information flows, where culture is mediated and enacted...

  12. Affective Maps

    DEFF Research Database (Denmark)

    Salovaara-Moring, Inka

    . In particular, mapping environmental damage, endangered species, and human made disasters has become one of the focal point of affective knowledge production. These ‘more-than-humangeographies’ practices include notions of species, space and territory, and movement towards a new political ecology. This type...... of digital cartographies has been highlighted as the ‘processual turn’ in critical cartography, whereas in related computational journalism it can be seen as an interactive and iterative process of mapping complex and fragile ecological developments. This paper looks at computer-assisted cartography as part...... of environmental knowledge production. It uses InfoAmazonia, the databased platform on Amazon rainforests, as an example of affective geo-visualization within information mapping that enhances embodiment in the experience of the information. Amazonia is defined as a digitally created affective (map)space within...

  13. INSULIN ANALOGUES: ANALYSIS OF PROLIFERATIVE POTENCY AND CHARACTERIZATION OF RECEPTORS AND SIGNALLING PATHWAYS ACTIVATED IN HUMAN MAMMARY EPITHELIAL CELLS

    OpenAIRE

    Shukla, Ashish

    2009-01-01

    Insulin analogues have been developed with the aim to provide better glycaemic control to diabetic patients. They are generated by modifying the insulin backbone which, however, may alter relevant biochemical characteristics such as the affinity to insulin receptor and type I insulin-like growth factor receptor (IGF-IR), and the insulin receptor dissociation rate. As a result insulin analogues may exhibit stronger mitogenic potency than regular insulin. Normal mammary epithelial cells show hi...

  14. Evaluation of different extraction methods on antimicrobial potency of Adenium obesum stem against food borne pathogenic bacterial strains in Oman

    OpenAIRE

    Mohammad Amzad Hossain; Tahiya Hilal Ali Al-Abri; Amira Hamood Salim Al-Musalami; Md. Sohail Akhtar; Sadri Said

    2014-01-01

    Objective: To determine and compare the effect on antimicrobial potency of crude stems extract of Adenium obesum (A. obesum) by Soxhlet and maceration extraction methods. Methods: The crude extracts were prepared from the coarse samples of stems with methanol by using Soxhlet and maceration extraction methods. Both the crude extracts from two extraction methods were dissolved in water and successively extracted by different polarities solvents with increasing polarities. In vit...

  15. Improving animal welfare and reducing animal use for veterinary vaccine potency testing: state of the science and future directions

    OpenAIRE

    STOKES William; BROWN Karen; KULPA-EDDY Jodie; SRINIVAS Geetha; HALDER Maria; DRAAYER Hans; GALVIN Jeffrey; CLAASEN Ivo; GIFFORD Glen; WOODLAND Ralph; DOELLING Vivian; JONES Brett

    2011-01-01

    Veterinary vaccines contribute to improved human and animal health and welfare by preventing diseases and deaths caused by a wide range of infectious agents. However, testing necessary to ensure vaccine effectiveness and safety can involve large numbers of animals and significant pain and distress. NICEATM and ICCVAM convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing methods and to identify opportunities to advance ...

  16. Affect Regulation

    DEFF Research Database (Denmark)

    Pedersen, Signe Holm; Poulsen, Stig Bernt; Lunn, Susanne

    2014-01-01

    Gergely and colleagues’ state that their Social Biofeedback Theory of Parental Affect Mirroring” can be seen as a kind of operationalization of the classical psychoanalytic concepts of holding, containing and mirroring. This article examines to what extent the social biofeedback theory of parenta...

  17. 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 (C3...... selectivity to C2 and C3 resulted from broad differences in SCFAs potency at the mouse orthologs. In studies to define the molecular basis for these observations, marked variation in ligand-independent constitutive activity was identified using a [(35)S]GTPγS assay. The orthologs with higher potency...

  18. 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.

  19. Development of a robust and validated 2D-QSPR model for sweetness potency of diverse functional organic molecules.

    Science.gov (United States)

    Ojha, Probir Kumar; Roy, Kunal

    2018-02-01

    In the present report, we have developed a predictive QSPR model using only easily computable two-dimensional (2D) descriptors from diverse classes of sweetening agents to find out the key structural properties which regulate their sweet potency. The available data set was curated to remove salts, mixtures and compounds without having a definite structure. A k-fold double cross validation technique was employed for variable selection prior to development of the final model. The final model was developed using partial least squares (PLS) regression analysis and selected based on a mean absolute error (MAE) based criteria for the validation sets. The model was validated extensively using different internal and external validation strategies in accordance with the Organization for Economic Co-operation and Development (OECD) guidelines. This work presented development of a validated quantitative structure-property relationship (QSPR) model obtained from k-fold double cross-validation technique in order to find out the key structural information required to enhance the sweet potency of the molecules. Finally, we have designed and proposed 13 new molecules based on the insights obtained from the QSPR model. The designed compounds showed good in silico predicted sweetness potency with acceptable ADMET profile. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. The sweetness concentration-response of r,r-monatin, a naturally occurring high-potency sweetener.

    Science.gov (United States)

    Fry, John C; Yurttas, Nese; Biermann, Kari L; Lindley, Michael G; Goulson, Melanie J

    2012-10-01

    Monatin, known by the common and usual name arruva, is a zero-calorie, high-potency sweetener naturally occurring in the plant Sclerochiton ilicifolius A.Meeuse. The sweetness concentration-response (C-R) behavior of the most potent isomer (R,R-) in room-temperature (21 °C) water was determined using two-alternative forced choice discrimination tests with a minimum of 69 tasters. Results were processed by a method previously published to obtain isosweet concentrations of sucrose for 8 monatin concentrations up to 240 mg/L. These were used to construct a C-R plot. The equation for the resultant hyperbolic curve relating sucrose equivalent (SE,%) to monatin concentration ([monatin], mg/L) was SE = 26.7 ×[monatin]/(69.6 +[monatin]). R,R-monatin has a potency above 3000 at 5% sucrose equivalent, making it one of the most potently sweet naturally occurring substances known. Monatin is a naturally occurring, zero-calorie, high-potency sweetener. We have measured the sweetness of monatin over a range of concentrations. This information will help developers of zero-, low- and reduced-calorie products formulate with monatin. © 2012 Cargill, Inc. Journal of Food Science © 2012 Institute of Food Technologists®

  1. 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.

  2. The role of peer respect in linking abusive supervision to follower outcomes: Dual moderation of group potency.

    Science.gov (United States)

    Schaubroeck, John M; Peng, Ann C; Hannah, Sean T

    2016-02-01

    We develop a model in which abusive supervision undermines individuals' perceptions of the level of respect they are accorded by their group peers, which in turn reduces their performance and disconnects them psychologically from the organization. High group potency strengthens each of these connections. We studied the theorized relationships across 3 periods during a 10-week residential organizational entry program. Group potency, representing shared group perceptions, moderated relationships at the individual level. These included the negative relationship between abusive supervision (Time 1) and perceived peer respect (Time 2) and the relationship between perceived peer respect and organizational commitment, organizational identification, and turnover intention (Time 3). We found stronger relationships between abusive supervision and perceived peer respect--and between peer respect and the attitudinal outcomes and turnover intention--among groups with higher potency. Perceived peer respect was also positively related to followers' task performance. We discuss implications of the conceptual framework and findings for future research and theory development concerning how groups and individuals respond to abusive supervision and to treatment by their peers. (c) 2016 APA, all rights reserved).

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Cannabis policies and user practices: market separation, price, potency, and accessibility in Amsterdam and San Francisco.

    Science.gov (United States)

    Reinarman, Craig

    2009-01-01

    This paper explores user perceptions and practices in contrasting legal-policy milieux-Amsterdam (de facto decriminalization) and San Francisco (de jure criminalization) on four policy issues: sources of cannabis and separation of markets for it and other drugs; user perceptions of effects of price on consumption; effects of potency on consumption; and perceived risk of arrest and accessibility of cannabis. Questions on these issues were added to surveys on career use patterns amongst representative samples of experienced cannabis users using comparable methods. Most San Francisco respondents obtained cannabis through friends who knew dealers, whereas most Amsterdam respondents obtained it from regulated shops. Only one in seven Amsterdam respondents but half the San Francisco respondents could obtain other drugs from their cannabis sources. Majorities under both systems had never found cannabis "too expensive." Amsterdam respondents preferred milder cannabis whilst San Francisco respondents preferred stronger; majorities in both cities reported self-titrating with potent cannabis. Risk and fear of arrest were higher in San Francisco, but most in both cities perceived arrest as unlikely. Estimated search times were somewhat longer in San Francisco, but a majority reported being able to access it within half a day. There is substantial separation of markets in the Dutch system. Policies designed to increase cannabis prices appear unlikely to impact consumption. Decriminalization was associated with a preference for milder cannabis, but under both policy regimes most respondents self-titrated when using more potent strains. Criminalization was associated with somewhat higher risk and fear of arrest and somewhat longer search times, but these did not appear to significantly impede access for most respondents.

  8. Stem cells expanded from the human embryonic hindbrain stably retain regional specification and high neurogenic potency.

    Science.gov (United States)

    Tailor, Jignesh; Kittappa, Raja; Leto, Ketty; Gates, Monte; Borel, Melodie; Paulsen, Ole; Spitzer, Sonia; Karadottir, Ragnhildur Thora; Rossi, Ferdinando; Falk, Anna; Smith, Austin

    2013-07-24

    Stem cell lines that faithfully maintain the regional identity and developmental potency of progenitors in the human brain would create new opportunities in developmental neurobiology and provide a resource for generating specialized human neurons. However, to date, neural progenitor cultures derived from the human brain have either been short-lived or exhibit restricted, predominantly glial, differentiation capacity. Pluripotent stem cells are an alternative source, but to ascertain definitively the identity and fidelity of cell types generated solely in vitro is problematic. Here, we show that hindbrain neuroepithelial stem (hbNES) cells can be derived and massively expanded from early human embryos (week 5-7, Carnegie stage 15-17). These cell lines are propagated in adherent culture in the presence of EGF and FGF2 and retain progenitor characteristics, including SOX1 expression, formation of rosette-like structures, and high neurogenic capacity. They generate GABAergic, glutamatergic and, at lower frequency, serotonergic neurons. Importantly, hbNES cells stably maintain hindbrain specification and generate upper rhombic lip derivatives on exposure to bone morphogenetic protein (BMP). When grafted into neonatal rat brain, they show potential for integration into cerebellar development and produce cerebellar granule-like cells, albeit at low frequency. hbNES cells offer a new system to study human cerebellar specification and development and to model diseases of the hindbrain. They also provide a benchmark for the production of similar long-term neuroepithelial-like stem cells (lt-NES) from pluripotent cell lines. To our knowledge, hbNES cells are the first demonstration of highly expandable neuroepithelial stem cells derived from the human embryo without genetic immortalization.

  9. 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

  10. 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.

  11. 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.

  12. Increased potency and binding of mazindol to putative brain anorectic receptors in obesity-prone rats.

    Science.gov (United States)

    Levin, B E; Brown, K L; Vincent, G

    1994-12-30

    A class of sodium-sensitive, low affinity binding sites in the brain recognizes [3H]mazindol (MAZ). Competition for [3H]MAZ binding at these sites correlates with the anorectic potency of various phenethylamine drugs suggesting that these might be anorectic binding sites. Here [3H]MAZ binding, in the absence of sodium, was assessed by quantitative receptor autoradiography in rat brain. Binding was saturable, widespread and heterogenous with Kd = 3-229 microM and Bmax = 0.64-21.9 nmol/mg protein in various brain areas. By saturation studies, highest binding was in the somatosensory cortex, central amygdalar nucleus and bed nucleus of the stria terminalis. Hypothalamic subnuclei had intermediate and the piriform cortex had low binding. Rats were identified as prone to develop (DIO-prone) or resist (DR-prone) diet-induced obesity by their low vs. high 24 h urine norepinephrine excretion, respectively. While similar in body weight and basal 30 min intake of 4% sucrose, DIO-prone rats had 28% greater inhibition of sucrose intake by 3 mg/kg MAZ, i.p. (86 +/- 5%) than DR-prone rats (67 +/- 6%; P = 0.05). DIO-prone rats also had 23-55% higher levels of 10 nM [3H]MAZ binding in various hypothalamic and amygdalar nuclei, the somatosensory, piriform and gustatory cortices and thalamus. Given their greater sensitivity the highest dose of MAZ used and their higher binding of MAZ to putative brain anorectic receptors, DIO-prone rats might have a deficiency of an endogenous satiety factor which could predispose them to develop obesity when challenged with high energy, high sucrose diets.

  13. 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.

  14. Application of agonist-receptor modeling to the sweetness synergy between high fructose corn syrup and sucralose, and between high-potency sweeteners.

    Science.gov (United States)

    Wolf, P A; Bridges, J R; Wicklund, R

    2010-03-01

    The agonist-receptor-transducer model of D. Ennis is applied to beverage formulations sweetened with high fructose corn syrup, sucralose, and other high-potency sweeteners, confirming the utility of the model, and supports the growing volume of evidence for multiple binding sites on the sweetness receptor. The model is further simplified to require less parameters for other sweetener blend systems whenever potency information is available for the single sweeteners.

  15. Synthesis and Potency of Novel Uracil Nucleotides and Derivatives as P2Y2 and P2Y6 Receptor Agonists

    OpenAIRE

    Ko, Hyojin; Carter, Rhonda L.; Cosyn, Liesbet; Petrelli, Riccardo; de Castro, Sonia; Besada, Pedro; Zhou, Yixing; Cappellacci, Loredana; Franchetti, Palmarisa; Grifantini, Mario; Van Calenbergh, Serge; Harden, T. Kendall; Jacobson, Kenneth A.

    2008-01-01

    The phosphate, uracil, and ribose moieties of uracil nucleotides were varied structurally for evaluation of agonist activity at the human P2Y2, P2Y4, and P2Y6 receptors. The 2-thio modification, found previously to enhance P2Y2 receptor potency, could be combined with other favorable modifications to produce novel molecules that exhibit high potencies and receptor selectivities. Phosphonomethylene bridges introduced for stability in analogues of UDP, UTP and uracil dinucleotides markedly redu...

  16. Influence of age and ways of treatment in the parasitemia in mice infected with Trypanosoma cruzi treated with high potency biotherapy

    OpenAIRE

    Silvana Marques de Araujo; Fabiana Nabarro Ferraz; Camila Fernanda Brustolin; Neide Martins Moreira; Caroline Felicio Braga; Paula Fernanda Massini; Denise Lessa Aleixo

    2011-01-01

    Introduction: The infection of mice by Trypanosoma cruzi is well known, making this a good model for understanding the effect of highly diluted medications. Mice of different ages show different responses to biotherapic T. cruzi [1]. Other data from our laboratory using biotherapic treatment at low potencies show that long lasting treatment has a better effect in mice infected with T. cruzi. However, the use of high potency biotherapics in mice of different ages infected with T. cruzi has not...

  17. Affective Maps

    DEFF Research Database (Denmark)

    Salovaara-Moring, Inka

    . In particular, mapping environmental damage, endangered species, and human made disasters has become one of the focal point of affective knowledge production. These ‘more-than-humangeographies’ practices include notions of species, space and territory, and movement towards a new political ecology. This type...... of digital cartographies has been highlighted as the ‘processual turn’ in critical cartography, whereas in related computational journalism it can be seen as an interactive and iterative process of mapping complex and fragile ecological developments. This paper looks at computer-assisted cartography as part...

  18. Nutrient Potency of Rice Straw Processed with Amofer as Cattle Feed Stuff in East Kalimantan

    Directory of Open Access Journals (Sweden)

    Hamdi Mayulu

    2015-12-01

    Full Text Available Forage demand can be supplied from rice straw which processed with certain feed technology innovation. Some advantages can be derived under this technology i.e. increasing nutrient content, optimizing the utilization, improving the efficiency and reducing production cost by minimizing feed cost. Ammoniation fermentation (amofer as an applied technology could give solution over the limitation of rice straw availability. The objective of this research was to determine the potency of rice straw processed with amofer (amofer-rice straw as raw material to formulate complete feed. The experiment was carried out with randomized block design with three treatments and six replications. Amofer treatment was carried out by adding urea 3% from the total material and then placed into plastic jar +12 liter and then incubated under an-aerobic process for 18 days. Fermentation material i.e. biology starter by 1% of total material was added at the ninth day. Dry Matter (DM content resulted from each treatments was 87,28%, 85,96% and 84,61% for T1, T2 and T3, respectively. Crude Protein (CP content was T1=24,48%, T2=21,04%; and T3=24,46%, Crude Fiber (CF content was T1=31,30%; T2=31,30%; and T3=31,39%. Total Digestible Nutrient (TDN for version 1 was  T1=57,29; T2=56,19; and T3=56,89 and version 2 was T1=53,11%; T2=52,28%; and T3=51,10%. The average value of Non Nitrogen Free Extract (NNFE was T1=23,49%; T2=28,08%; and T3=26,57%. The utilization of amofer as applicable technology is considered as the most appropriate method to increase the quality of rice straw by significantly increase nutrient content in term of crude protein (CP and reduce crude fiber (CF content. This increasing quality can be seen from the result of proximate analysis, NNFE and TDN content

  19. 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

  20. 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

  1. 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

  2. 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.

  3. The Effect of Teaching Vocabulary through Semantic Mapping on EFL Learners' Awareness of the Affective Dimensions of Deep Vocabulary Knowledge

    Science.gov (United States)

    Nilforoushan, Somayeh

    2012-01-01

    This study focused on the effect of teaching vocabulary through semantic mapping on the awareness of two affective dimensions, evaluation and potency dimensions of deep vocabulary knowledge as well as the general vocabulary knowledge of EFL students. Sixty intermediate EFL female adult learners participated in this study; they were chosen among 90…

  4. [Affective dependency].

    Science.gov (United States)

    Scantamburlo, G; Pitchot, W; Ansseau, M

    2013-01-01

    Affective dependency is characterized by emotional distress (insecure attachment) and dependency to another person with a low self-esteem and reassurance need. The paper proposes a reflection on the definition of emotional dependency and the confusion caused by various denominations. Overprotective and authoritarian parenting, cultural and socio-environmental factors may contribute to the development of dependent personality. Psychological epigenetic factors, such as early socio-emotional trauma could on neuronal circuits in prefronto-limbic regions that are essential for emotional behaviour.We also focus on the interrelations between dependent personality, domestic violence and addictions. The objective for the clinician is to propose a restoration of self-esteem and therapeutic strategies focused on autonomy.

  5. Development of a flow cytometric bead immunoassay and its assessment as a possible aid to potency evaluation of enterotoxaemia vaccines

    Directory of Open Access Journals (Sweden)

    Angela Buys

    2014-03-01

    Full Text Available Enterotoxaemia, an economically important disease of sheep, goats and calves, is caused by systemic effects of the epsilon toxin produced by the anaerobic bacterium Clostridium perfringens type D. The only practical means of controlling the occurrence of enterotoxaemia is to immunise animals by vaccination. The vaccine is prepared by deriving a toxoid from the bacterial culture filtrate and the potency of the vaccine is tested with the in vivo mouse neutralisation test (MNT. Due to ethical, economic and technical reasons, alternative in vitro assays are needed. In this study an indirect cytometric bead immunoassay (I-CBA was developed for use in vaccine potency testing and the results were compared with those obtained using an indirect enzyme-linked immunosorbent assay (I-ELISA and the MNT. Sera were collected from guinea pigs immunised with three different production batches of enterotoxaemia vaccine and the levels of anti-epsilon toxin antibodies were determined. Although the intra- and inter-assay variability was satisfactory, epsilon antitoxin levels determined by both the I-ELISA and indirect cytometric bead immunoassay (I-CBA tests were higher than those of the MNT assay. In contrast to the MNT, all of the serum samples were identified as having antitoxin levels above the required minimum (not less than 5 U/mL. These results indicate that the respective in vitro tests in their current formats are not yet suitable alternatives to the in vivo MNT. The growing demand for a more humane, cost-effective and efficient method for testing the potency of enterotoxaemia vaccines, however, provides a strong impetus for further optimisation and standardisation of the I-CBA assay but further analytical research is required.

  6. 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.

  7. Equivalent potency and pharmacokinetics of recombinant human growth hormones with or without an N-terminal methionine.

    Science.gov (United States)

    Moore, J A; Rudman, C G; MacLachlan, N J; Fuller, G B; Burnett, B; Frane, J W

    1988-06-01

    Two forms of human GH (hGH) have been produced by recombinant DNA technology. One form has an amino acid sequence identical to that of the natural pituitary hormone (rhGH) and the other form has an additional N-terminal methionine (Met-hGH). The biological potencies of these 2 polypeptides have been compared in hypophysectomized rats in a multidose study measuring body weights and several long bone growth parameters. The pharmacokinetic profiles after iv and sc injection were determined in cynomolgus monkeys in a 4-period cross-over study. All of the measured parameters in all the studies indicated that there was no difference in the two forms of hGH. Measurements taken after 27 daily injections of rhGH or Met-hGH (30-500 micrograms/kg.day) indicated that femur length and width of the proliferative zone in the tibial epiphysis showed dose-related effects for both forms of hGH but no difference between them. The relative potency, based on body weight gain, was calculated using a parallel line bioassay. Weight gain after 8 daily injections in the 5-dose long bone growth study indicated a rhGH potency of 0.80 (95% confidence interval, 0.5-1.23) relative to Met-hGH. It was concluded that the presence of an N-terminal methionine on hGH has no effect on potency in this model. The pharmacokinetic parameters after iv administration were estimated by fitting serum concentration-time data to a 2-compartment model. Parameters after sc injection were computed by compartment-independent methods. Met-hGH and rhGH had very similar pharmacokinetic profiles after both routes of administration. Comparison of the pharmacokinetic parameters indicated that the clearance after iv administration (rhGH, 15 ml/min; Met-hGH, 13 ml/min) and the sc bioavailability (rhGH, 0.72 +/- 0.21; Met-hGH, 0.59 +/- 0.21) were not significantly different for the 2 forms of hGH. It was concluded that rhGH and Met-hGH have equivalent bioavailability and pharmacokinetics in cynomolgus monkeys.

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

    OpenAIRE

    Cheng, Bing-Ho; Sheen, Lee-Yan; Chang, Shang-Tzen

    2014-01-01

    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 hydroc...

  9. 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

  10. 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...

  11. 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.

  12. 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.

  13. 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.

  14. Comparing clinical effectiveness and drug toxicity with hydrochlorothiazide and chlorthalidone using two potency ratios in a managed care population.

    Science.gov (United States)

    Saseen, Joseph J; Ghushchyan, Vahram; Nair, Kavita V

    2015-02-01

    This study compared the clinical effectiveness and drug toxicity of chlorthalidone and hydrochlorothiazide. Electronic health records and claims data were used to identify patients initially prescribed chlorthalidone or hydrochlorothiazide. A total of 214 patients prescribed chlorthalidone 25 mg were matched with 428 patients prescribed hydrochlorothiazide 25 mg (1:1 potency ratio) and 214 patients prescribed hydrochlorothiazide 50 mg (1:2 potency ratio). Mean systolic blood pressure/diastolic blood pressure values at least 30 days after initial prescription were lower with chlorthalidone (132.2/74 mm Hg) compared with hydrochlorothiazide 25 mg (137.0/77.5 mm Hg) and hydrochlorothiazide 50 mg (138.6/78.5 mm Hg) (Phydrochlorothiazide 25 mg (32.1%/63.9%) or hydrochlorothiazide 50 mg (32.8%/68.9%) (Phydrochlorothiazide 25 mg (Phydrochlorothiazide 50 mg. These findings indicate that chlorthalidone 25 mg is associated with a better antihypertensive response than hydrochlorothiazide 25 mg or 50 mg, without clinically significant differences in serum potassium. © 2014 Wiley Periodicals, Inc.

  15. Fluctuation of the dopamine uptake inhibition potency of cocaine, but not amphetamine, at mammalian cells expressing the dopamine transporter

    Science.gov (United States)

    Ukairo, Okechukwu T.; Ramanujapuram, Suneetha; Surratt, Christopher K.

    2007-01-01

    Cocaine, amphetamines and other psychostimulants inhibit synaptic dopamine uptake by interfering with dopamine transporter (DAT) function. The resultant potentiation of dopaminergic neurotransmission is associated with psychostimulant addiction. Fluctuations in dopamine uptake inhibition potency (DUIP) were observed for classical DAT blockers including cocaine, mazindol, methylphenidate (Ritalin™) and benztropine in CHO cells expressing wildtype DAT; cocaine potency also decreased in DAT-expressing non-neuronal COS-7 cells and neuronal N2A neuroblastoma cells. In contrast, the DAT substrate (+)-amphetamine did not display this DUIP fluctuation. In parallel experiments, no fluctuation was observed for the apparent binding affinities of these 5 drugs. The DUIP decrease appeared to correlate with an increase in cell surface DAT expression level, as measured by Bmax values and confocal microscopy. The fact that the DUIP profile of amphetamine diverged from that of the classical DAT blockers is consistent with the idea of fundamental differences between the mechanisms of abused psychostimulant DAT substrates and inhibitors. Identification of the cellular factors that underlie the DAT inhibitor DUIP fluctuation phenomenon may be relevant to anti-psychostimulant drug discovery efforts. PMID:17169338

  16. 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.

  17. THE DEVELOPMENT OF SCIENTIFIC-APPROACH-BASED LEARNING INSTRUMENTSINTEGRATED WITH RED ONION FARMING POTENCY IN BREBES INDONESIA

    Directory of Open Access Journals (Sweden)

    D. Setiawan

    2016-04-01

    Full Text Available This study aimed to describe the eligibility category of science learning instrument based on scientific approach integrated with onion farming potency. Also, this study aimed to analyze the effectiveness of the application of the science learning instrument in terms ofscience process skills development and the cognitive learning outcomes in the student of class VII SMPN 1 Bulakamba.This study used thedevelopment research methods by adapting the 4D model that includes define, design, develop, and disseminate. The learning instruments developed in this research were the learning implementation plan (RPP and the student worksheet (LKS. The data collection was done by using non-test technique using interview guides, product validation sheet, students’ response sheet to the readability of LKS and the instructional observation sheets; as well as using theworksheet of process skills and cognitive learning outcomes. The results showed that the eligibility of the science learning instruments integrated with onion farming potency was categorized as excellent. The application of scientific-approach-based learning instruments was effective to improve the process skills and the students’ cognitive learning outcomes in class VII SMPN 1 Bulakamba.

  18. 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.

  19. D-Isonucleotide (isoNA) incorporation around cleavage site of passenger strand promotes the vibration of Ago2-PAZ domain and enhances in vitro potency of siRNA.

    Science.gov (United States)

    Huang, Ye; Tian, Miao; Zhang, Yichao; Sheng, Gang; Chen, Zhuo; Ma, Yuan; Chen, Yue; Peng, Yihong; Zhao, Yi-Lei; Wang, Yanli; Zhang, Lihe; Yang, Zhenjun

    2015-11-28

    It has been demonstrated that passenger strand cleavage is important for the activation of RNA-induced silencing complex (RISC), which is a crucial step for siRNA-mediated gene silencing. Herein, we report that isonucleotide (isoNA) modification around the cleavage site of the passenger strand would affect the in vitro potency of modified siRNAs by altering the motion pattern of the Ago2-PAZ domain. According to western blotting, q-PCR and antiviral test results, we proved that D-isonucleotide (isoNA) modification at the position 8 of the passenger strand (siMek1-S08D), which is adjacent to the cleavage site, markedly improved the in vitro potency of the modified siRNA, whereas siRNAs with D-isoNA incorporation at position 9 (siMek1-S09D) or L-isoNA incorporation at positions 8 and 9 (siMek1-S08L, siMek1-S09L) displayed lower activity compared to native siRNA. Kinetics evaluation of passenger strand cleavage induced by T. thermophilus Ago (Tt-Ago) showed that D-isoNA modification at position 8 of the passenger strand had no significant influence on the cleavage rate, but L-isoNA modification at position 8 slowed the cleavage rate markedly. Moreover, the results of molecular dynamics simulations showed that D-isoNA modification at position 8 affected the open-close motion of the PAZ domain in the Ago/siRNA complex, which may promote the loading of RISC and release of a passenger strand cleavage product, and consequently accelerate the activation of RISC and enhance silencing activity. However, D-isoNA modification at position 9 or L-isoNA modification at position 8 or 9 exerted opposite influences on the motion of the Ago-PAZ domain.

  20. A step forward in the quality control testing of inactivated rabies vaccines - extensive evaluation of European vaccines by using alternative methods to the in vivo potency tests.

    Science.gov (United States)

    Servat, Alexandre; Kempff, Sébastien; Brogat, Valère; Litaize, Estelle; Schereffer, Jean-Luc; Cliquet, Florence

    2015-03-01

    The mouse challenge test still remains the reference method for the potency determination of human and animal inactivated rabies vaccines, and it is still widely used throughout the world. This test suffers from many disadvantages - it is expensive and time consuming, uses a large number of mice, causes significant animal distress, and suffers from high variability. Recently, the European Pharmacopoeia has recognised the use of a serological potency assay (SPA) as an alternative method to the challenge test. This new test is based on the determination of rabies neutralising antibody titres in vaccinated mice, by using the modified Rapid Fluorescent Focus Inhibition Test (mRFFIT). With the objective of adopting this new method for the batch release of inactivated rabies vaccines, we evaluated its performance on a large collection of rabies vaccines currently assessed in our laboratory. The Fluorescent Antibody Virus Neutralisation test (FAVNt) was used in parallel with the mRFFIT, and the results were compared to the mouse challenge test. Our results demonstrate that the SPA is capable of estimating the potency of vaccines formulated with a potency margin well above the minimum of 1IU/dose. For low potency vaccines, this new method demonstrated some limitations, due to the recurrent invalidation of the assay. We have also demonstrated the superior sensitivity of the FAVNt when compared to the mRFFIT, and the importance of minimising the risk of detecting non-responders in vaccinated mice. 2015 FRAME.

  1. 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.

  2. Accounting for data variability, a key factor in in vivo/in vitro relationships: application to the skin sensitization potency (in vivo LLNA versus in vitro DPRA) example.

    Science.gov (United States)

    Dimitrov, S; Detroyer, A; Piroird, C; Gomes, C; Eilstein, J; Pauloin, T; Kuseva, C; Ivanova, H; Popova, I; Karakolev, Y; Ringeissen, S; Mekenyan, O

    2016-12-01

    When searching for alternative methods to animal testing, confidently rescaling an in vitro result to the corresponding in vivo classification is still a challenging problem. Although one of the most important factors affecting good correlation is sample characteristics, they are very rarely integrated into correlation studies. Usually, in these studies, it is implicitly assumed that both compared values are error-free numbers, which they are not. In this work, we propose a general methodology to analyze and integrate data variability and thus confidence estimation when rescaling from one test to another. The methodology is demonstrated through the case study of rescaling the in vitro Direct Peptide Reactivity Assay (DPRA) reactivity to the in vivo Local Lymph Node Assay (LLNA) skin sensitization potency classifications. In a first step, a comprehensive statistical analysis evaluating the reliability and variability of LLNA and DPRA as such was done. These results allowed us to link the concept of gray zones and confidence probability, which in turn represents a new perspective for a more precise knowledge of the classification of chemicals within their in vivo OR in vitro test. Next, the novelty and practical value of our methodology introducing variability into the threshold optimization between the in vitro AND in vivo test resides in the fact that it attributes a confidence probability to the predicted classification. The methodology, classification and screening approach presented in this study are not restricted to skin sensitization only. They could be helpful also for fate, toxicity and health hazard assessment where plenty of in vitro and in chemico assays and/or QSARs models are available. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. 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.

  4. 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.

  5. Spectrum and potency of ceftaroline tested against leading pathogens causing community-acquired respiratory tract infections in Europe (2010).

    Science.gov (United States)

    Farrell, David J; Flamm, Robert K; Jones, Ronald N; Sader, Helio S

    2013-01-01

    Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a novel cephalosporin exhibiting in vitro bactericidal activity against Gram-positive organisms, including Streptococcus pneumoniae and methicillin-susceptible and -resistant Staphylococcus aureus, as well as common Gram-negative organisms. The objective of this study was to determine the spectrum and potency of ceftaroline against recent leading pathogens causing community-acquired respiratory tract infections (CARTI) isolated in Europe. A total of 1563 isolates from the 2010 Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) Program were identified as CARTI pathogens by the infection type and/or specimen type recorded by the participating laboratory. Isolates were collected from patients in 52 medical centers located in 19 European countries (including Israel and Turkey). Susceptibility testing for ceftaroline and commonly used antimicrobials was performed by Clinical and Laboratory Standards Institute (CLSI) broth microdilution methodology. Susceptibility interpretations for comparators were as published in CLSI and the European Committee on Antimicrobial Susceptibility Testing guidelines, and for ceftaroline US-FDA breakpoints were also applied. Ceftaroline was very active overall against 799 S. pneumoniae (MIC(50/90,) ≤ 0.008/0.12 μg/mL) and inhibited 100.0% of all isolates at a MIC ≤ 0.5 μg/mL. Ceftaroline was very potent against penicillin-resistant (CLSI oral penicillin V breakpoints) and -intermediate S. pneumoniae (MIC(50/90), 0.12/0.25 and 0.03/0.12 μg/mL, respectively), but potency was lower than observed against penicillin-susceptible isolates (MIC(50/90), ≤ 0.008/≤ 0.008 μg/mL). Ceftaroline was also very active (MIC(50/90), ≤ 0.008/0.015 μg/mL) against 515 Haemophilus influenzae, including β-lactamase-producing strains (MIC(50/90), 0.015/0.06 μg/mL). Ceftaroline also demonstrated good activity against 205 Moraxella catarrhalis isolates (MIC(50

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. Open source software implementation of an integrated testing strategy for skin sensitization potency based on a Bayesian network.

    Science.gov (United States)

    Pirone, Jason R; Smith, Marjolein; Kleinstreuer, Nicole C; Burns, Thomas A; Strickland, Judy; Dancik, Yuri; Morris, Richard; Rinckel, Lori A; Casey, Warren; Jaworska, Joanna S

    2014-01-01

    An open-source implementation of a previously published integrated testing strategy (ITS) for skin sensitization using a Bayesian network has been developed using R, a free and open-source statistical computing language. The ITS model provides probabilistic predictions of skin sensitization potency based on in silico and in vitro information as well as skin penetration characteristics from a published bioavailability model (Kasting et al., 2008). The structure of the Bayesian network was designed to be consistent with the adverse outcome pathway published by the OECD (Jaworska et al., 2011, 2013). In this paper, the previously published data set (Jaworska et al., 2013) is improved by two data corrections and a modified application of the Kasting model. The new data set implemented in the original commercial software package and the new R version produced consistent results. The data and a fully documented version of the code are publicly available (http://ntp.niehs.nih.gov/go/its).

  12. 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

  13. Procedure for Calculation of Potency and Efficacy for Ligands Acting on G(s)- and G (i)-Coupled Receptors

    DEFF Research Database (Denmark)

    Meier, Eddi; Schousboe, Arne; Belhage, Bo

    2012-01-01

    rank orders will therefore change considerably, when estimations are based on incorrect calculation of the original experimental results. Thus, the only correct way to calculate effect data on which to base E(MAX) and EC(50) estimations is to use cAMP concentrations derived from transformation......Structure activity relationship (SAR) analyses of pharmacological data of compounds constitute an important part of the discovery process in the design of new drug candidates with improved pharmacological properties. In particular G-Protein Coupled Receptors (GPCRs) associated with the cAMP second....... It appears, however, to be a common practice to omit the use of cAMP standard curves to transform the measured signals (cpm or cps) into cAMP concentrations on which estimations of potencies (EC(50) values) and efficacies (E(MAX) values) in G(s) and G(i) coupled receptor stimulation are based. Such practice...

  14. Passive air sampler as a tool for long-term air pollution monitoring: Part 2. Air genotoxic potency screening assessment

    International Nuclear Information System (INIS)

    Cupr, Pavel; Klanova, Jana; Bartos, Tomas; Flegrova, Zuzana; Kohoutek, Jiri; Holoubek, Ivan

    2006-01-01

    The capability of passive air sampling to be employed in the evaluation of direct genotoxicity of ambient air samples was assessed. Genotoxic effects of the total extracts from the polyurethane foam filters exposed for 28 days during a regional passive air sampling campaign were investigated. Twenty sampling sites were selected in Brno city on the area of approximately 20 x 20 km in October and November 2004. Brno is the second largest city of the Czech Republic, highly industrialized with approximately 370,000 of permanent inhabitants. The levels of PAHs, PCBs, and chlorinated pesticides were determined in all samples. Fraction of each extract was also assayed in the bacterial genotoxicity test using Escherichia coli sulA::lacZ. Complete dose-response relationships of the air extracts were determined. The statistical analysis showed significant correlation between observed biological effects and PAHs concentrations in samples. - Extracts from passive air samples can be used to assess genotoxic potency

  15. 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.

  16. 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

    2014-11-01

    Cannabis use is associated with an earlier age of onset of psychosis (AOP). However, the reasons for this remain debated. 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. 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. Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users. © The Author 2013. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  17. Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro

    Science.gov (United States)

    Thomas, A; Baillie, G L; Phillips, A M; Razdan, R K; Ross, R A; Pertwee, R G

    2007-01-01

    Background and purpose: A nonpsychoactive constituent of the cannabis plant, cannabidiol has been demonstrated to have low affinity for both cannabinoid CB1 and CB2 receptors. We have shown previously that cannabidiol can enhance electrically evoked contractions of the mouse vas deferens, suggestive of inverse agonism. We have also shown that cannabidiol can antagonize cannabinoid receptor agonists in this tissue with a greater potency than we would expect from its poor affinity for cannabinoid receptors. This study aimed to investigate whether these properties of cannabidiol extend to CB1 receptors expressed in mouse brain and to human CB2 receptors that have been transfected into CHO cells. Experimental approach: The [35S]GTPγS binding assay was used to determine both the efficacy of cannabidiol and the ability of cannabidiol to antagonize cannabinoid receptor agonists (CP55940 and R-(+)-WIN55212) at the mouse CB1 and the human CB2 receptor. Key results: This paper reports firstly that cannabidiol displays inverse agonism at the human CB2 receptor. Secondly, we demonstrate that cannabidiol is a high potency antagonist of cannabinoid receptor agonists in mouse brain and in membranes from CHO cells transfected with human CB2 receptors. Conclusions and implications: This study has provided the first evidence that cannabidiol can display CB2 receptor inverse agonism, an action that appears to be responsible for its antagonism of CP55940 at the human CB2 receptor. The ability of cannabidiol to behave as a CB2 receptor inverse agonist may contribute to its documented anti-inflammatory properties. PMID:17245363

  18. 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

  19. Effects of ocean acidification on the potency of macroalgal allelopathy to a common coral

    Science.gov (United States)

    Del Monaco, Carlos; Hay, Mark E.; Gartrell, Patrick; Mumby, Peter J.; Diaz-Pulido, Guillermo

    2017-02-01

    Many coral reefs have phase shifted from coral to macroalgal dominance. Ocean acidification (OA) due to elevated CO2 is hypothesised to advantage macroalgae over corals, contributing to these shifts, but the mechanisms affecting coral-macroalgal interactions under OA are unknown. Here, we show that (i) three common macroalgae are more damaging to a common coral when they compete under CO2 concentrations predicted to occur in 2050 and 2100 than under present-day conditions, (ii) that two macroalgae damage corals via allelopathy, and (iii) that one macroalga is allelopathic under conditions of elevated CO2, but not at ambient levels. Lipid-soluble, surface extracts from the macroalga Canistrocarpus (=Dictyota) cervicornis were significantly more damaging to the coral Acropora intermedia growing in the field if these extracts were from thalli grown under elevated vs ambient concentrations of CO2. Extracts from the macroalgae Chlorodesmis fastigiata and Amansia glomerata were not more potent when grown under elevated CO2. Our results demonstrate increasing OA advantages seaweeds over corals, that algal allelopathy can mediate coral-algal interactions, and that OA may enhance the allelopathy of some macroalgae. Other mechanisms also affect coral-macroalgal interactions under OA, and OA further suppresses the resilience of coral reefs suffering blooms of macroalgae.

  20. The Teratogenic Potencies of Valproic Acid Derivatives and Their Effects on Biological End-points are Related to Changes in Histone Deacetylase and Erk1/2 Activities

    DEFF Research Database (Denmark)

    Gotfryd, Kamil; Hansen, Maria; Kawa, Anna

    2011-01-01

    Valproic acid (VPA) is a known teratogen. In the present study, the effects of VPA and seven VPA derivatives with different teratogenic potencies (isobutyl-, 5-methyl-, ethyl-, propyl-, butyl-, pentyl- and hexyl-4-yn-VPA) were investigated in L929 cells in vitro. Evaluated end-points included cha...

  1. A Mechanism-based 3D-QSAR Approach for Classification and Prediction of Acetylcholinesterase Inhibitory Potency of Organophosphate and Carbamate Analogs

    Science.gov (United States)

    Organophosphate (OP) and carbamate esters can inhibit acetylcholinesterase (AChE) by binding covalently to a serine residue in the enzyme active site, and their inhibitory potency depends largely on affinity for the enzyme and the reactivity of the ester. Despite this understandi...

  2. 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

  3. 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

  4. 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

  5. Synthesis and potency of novel uracil nucleotides and derivatives as P2Y2 and P2Y6 receptor agonists.

    Science.gov (United States)

    Ko, Hyojin; Carter, Rhonda L; Cosyn, Liesbet; Petrelli, Riccardo; de Castro, Sonia; Besada, Pedro; Zhou, Yixing; Cappellacci, Loredana; Franchetti, Palmarisa; Grifantini, Mario; Van Calenbergh, Serge; Harden, T Kendall; Jacobson, Kenneth A

    2008-06-15

    The phosphate, uracil, and ribose moieties of uracil nucleotides were varied structurally for evaluation of agonist activity at the human P2Y(2), P2Y(4), and P2Y(6) receptors. The 2-thio modification, found previously to enhance P2Y(2) receptor potency, could be combined with other favorable modifications to produce novel molecules that exhibit high potencies and receptor selectivities. Phosphonomethylene bridges introduced for stability in analogues of UDP, UTP, and uracil dinucleotides markedly reduced potency. Truncation of dinucleotide agonists of the P2Y(2) receptor, in the form of Up(4)-sugars, indicated that a terminal uracil ring is not essential for moderate potency at this receptor and that specific SAR patterns are observed at this distal end of the molecule. Key compounds reported in this study include 9, alpha,beta-methylene-UDP, a P2Y(6) receptor agonist; 30, Up(4)-phenyl ester and 34, Up(4)-[1]glucose, selective P2Y(2) receptor agonists; dihalomethylene phosphonate analogues 16 and 41, selective P2Y(2) receptor agonists; 43, the 2-thio analogue of INS37217 (P(1)-(uridine-5')-P(4)-(2'-deoxycytidine-5')tetraphosphate), a potent and selective P2Y(2) receptor agonist.

  6. 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

  7. 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.

  8. Potency of isothiocyanates to induce luciferase reporter gene expression via the electrophile-responsive element from murine glutathione S-transferase Ya

    NARCIS (Netherlands)

    Vermeulen, M.; Boerboom, A.M.M.J.F.; Blankvoort, B.M.G.; Aarts, J.M.M.J.G.; Rietjens, I.M.C.M.; Bladeren, P.J. van; Vaes, W.H.J.

    2009-01-01

    Isothiocyanates are electrophiles that are able to induce phase II biotransformation enzyme gene expression via an electrophile-responsive element (EpRE) in the gene regulatory region. To study the potency of different isothiocyanates to induce the expression of EpRE-regulated genes, a Hepa-1c1c7

  9. Two-tiered keratinocyte assay: IL-18 production by NCTC2544 cells to determine the skin sensitizing capacity and an epidermal equivalent assay to determine sensitizer potency

    DEFF Research Database (Denmark)

    Teunis, Marc; Corsini, Emanuela; Smits, Mieke

    2012-01-01

    sensitizers (DNCB, resorcinol, PPD) and 1 non sensitizer (lactic acid) were tested in tier 1. DNCB (extreme) and resorcinol (moderate) were ranked according to their potency in tier 2. These assays were successfully transferred to laboratories that did not perform both assays previously. Second, the actual...

  10. 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...

  11. 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

  12. Immunomodulatory potencies of isolated compounds from Crataegus azarolus through their antioxidant activities.

    Science.gov (United States)

    Mustapha, Nadia; Mokdad-Bzéouich, Imèn; Sassi, Aicha; Abed, Besma; Ghedira, Kamel; Hennebelle, Thierry; Chekir-Ghedira, Leila

    2016-06-01

    The search of natural immunomodulatory agents has become an area of great interest in order to reduce damage to the human body. In this study, the immunomodulatory potential of Crataegus azarolus and its isolated hyperoside on mouse lymphocytes and macrophages in vitro was assessed. The effect of C. azarolus natural compounds on splenocytes proliferation, natural killer (NK) and cytotoxic T lymphocytes (CTL) activities, and on macrophage-mediated cytotoxicity were assessed by MTT test. Phagocytic activity and inhibition of nitric oxide (NO) release by macrophages were also evaluated. The antioxidant capacity of these products was evaluated by determining their cellular antioxidant activity (CAA) in splenocytes and macrophages. Depending on the concentrations, both ethyl acetate (EA) extract and hyperoside (Hyp) from C. azarolus affect macrophage functions by modulating their lysosomal enzyme activity and nitric oxide release. Whereas, the above-mentioned products significantly promote LPS and lectin-stimulated splenocyte proliferation, implying a potential activation of lymphocytes B and T enhancing humoral and cellular immune responses. Moreover, EA extract and Hyp could enhance the activity of NK and T lymphocytes cells, as well as the macrophages-mediated cytotoxicity against B16F10 cells. The anti-inflammatory activity was concomitant with the cellular antioxidant effect of the tested compounds against macrophages and splenocytes. Collectively, C. azarolus and its isolated hyperoside exhibited an immunomodulatory effect through their antioxidant activity. These findings suggest that C. azarolus should be explored as a novel potential immunomodulatory agent for the treatment of inflammatory diseases.

  13. Factors influencing the potency of marbofloxacin for pig pneumonia pathogens Actinobacillus pleuropneumoniae and Pasteurella multocida.

    Science.gov (United States)

    Dorey, L; Hobson, S; Lees, P

    2017-04-01

    For the pig respiratory tract pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida, Minimum Inhibitory Concentration (MIC) of marbofloxacin was determined in recommended broths and pig serum at three inoculum strengths. MICs in both growth matrices increased progressively from low, through medium to high starting inoculum counts, 10 4 , 10 6 and 10 8 CFU/mL, respectively. P. multocida MIC ratios for high:low inocula were 14:4:1 for broth and 28.2:1 for serum. Corresponding MIC ratios for A. pleuropneumoniae were lower, 4.1:1 (broth) and 9.2:1 (serum). MIC high:low ratios were therefore both growth matrix and bacterial species dependent. The effect of alterations to the chemical composition of broths and serum on MIC were also investigated. Neither adjusting broth or serum pH in six increments over the range 7.0 to 8.0 nor increasing calcium and magnesium concentrations of broth in seven incremental steps significantly affected MICs for either organism. In time-kill studies, the killing action of marbofloxacin had the characteristics of concentration dependency against both organisms in both growth matrices. It is concluded that MIC and time-kill data for marbofloxacin, generated in serum, might be preferable to broth data, for predicting dosages of marbofloxacin for clinical use. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Evaluation and comparison of Hela, Hep2C and Vero cell lines sensitivity to polio vaccinal virus using micro and macro vaccine potency tests

    Directory of Open Access Journals (Sweden)

    Soleimani, S.,

    2012-11-01

    Full Text Available Poliomyelitis, an acute viral infectious disease caused by poliovirus, still remains a public health problem in developing countries. Despite the global effort to eradicate polio, continuing the polio immunization with a potent and safe vaccine is essential. For accurate vaccine evaluation, three types of cell lines including Hela, Hep2C and Vero were evaluated and compared using two methods of polio vaccine potency tests (micro & macro. For cells comparison, five different batches from polio vaccines were tested and to develop the test, five variables including viruses, cells, serum, media and Co2 were studied. For validation, the titer of which has been well established as a working reference preparation (WRP was applied to control the accuracy and reproducibility of the testing system. Multiple comparisons were performed by analysis of variance (ANOVA followed by Tokey HDS and LSD. No significant differences were found between the potency of vaccine batches and between macro and micro methods. Reduction in cells sensitivity and potency of vaccines was found with increasing passage number. Significant differences were found between the sensitivity of the cell lines. The highest potency of polio vaccines was obtained using Hela cells (GMT in macro and micro test = 10 6.35; Hep2C cells were afterwards (GMT in macro= 10 6.01 and in micro test= 10 5.94; Vero cells were lowest (GMT in macro= 10 5.78 and in micro test= 10 5.72. So, the sensitivity and accuracy of the potency test for evaluation of the polio vaccine in immunization program in Iran will be assured using the Hela cell line with low passage number in macro and micro methods.

  15. Synergistic radical scavenging potency of curcumin-in-β-cyclodextrin-in-nanomagnetoliposomes

    Energy Technology Data Exchange (ETDEWEB)

    Aadinath, W.; Bhushani, Anu; Anandharamakrishnan, C., E-mail: anandhram@cftri.res.in

    2016-07-01

    Curcumin is a highly potent nutraceutical associated with various health benefits. However, its hydrophobic nature affects its bioavailability and bioactivity, and limits nutraceutical applications. Drug-in-cyclodextrin-in-liposome has the ability to mask the hydrophobic nature of drug and achieve better encapsulation. Also, encapsulating iron oxide nanoparticles (IONPs) within liposomes endow additional beneficial functionalities of IONPs. In the present study, curcumin-β-cyclodextrin inclusion complex (IC) and IONPs were co-encapsulated within liposomes (curcumin-in-β-cyclodextrin-in-nanomagnetoliposomes) to achieve the synergistic antioxidant potential of curcumin and IONPs. IC of curcumin-β-cyclodextrin was prepared by a simple rapid method and successful inclusion was confirmed by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR). Mean diameter of IONPs was found to be 180 nm and X-ray diffraction pattern confirmed the formation of hematite nanoparticles. Band gap energy calculated using absorption spectra was 2.25 eV, which falls in close proximity with the theoretically calculated values of hematite. Mean diameter of curcumin-in-β-cyclodextrin-in-nanomagnetoliposomes was 67 nm and encapsulation efficiency of curcumin was found to be 71%. Further, the co-encapsulated particles possessed significantly low IC{sub 50} value (64.7791 μg/ml, p < 0.01) compared to conventional curcumin liposome and IONPs, indicating its synergistically enhanced radical scavenging property. - Highlights: • Curcumin-in-β-cyclodextrin-in-nanomagnetoliposomes (mean diameter, 67 nm) has been prepared. • Encapsulation efficiency of curcumin was found to be 71%. • IONPs in the nano-carrier play dual role of targeted delivery and radical scavenging activities. • Conjunction of IONPs and curcumin into the liposomes increases the radical scavenging activity.

  16. Long-term exposure investigating the estrogenic potency of estriol in Japanese medaka (Oryzias latipes).

    Science.gov (United States)

    Lei, Bingli; Kang, Jia; Yu, Yingxin; Zha, Jinmiao; Li, Wei; Wang, Zijian; Wang, Yipei; Wen, Yu

    2014-03-01

    The growth, development, and ERα and Vtg-I gene expressions of Japanese ricefish (Oryzias latipes; medaka) exposed to different concentrations of estriol (E3), including one environmentally relevant concentration, during embryo-adult life stages were evaluated. At the early life stage, fertilized eggs were exposed to 5, 50, 500, 5000ng/L E3 for 15days, and the hatched fry were exposed continuously to the same concentrations for an additional 15days. Exposure to 500 and 5000ng/L E3 resulted in adverse effects on hatchability and time to hatching. At 5000ng/L, the gross abnormality rate was increased and the number of females that hatched was twice that of males. When the fish were exposed to 5-5000ng/L E3 for further 60days, the male hepatosomatic index (HSI) was increased at 5000ng/L. The female gonadosomatic index (GSI) was decreased at 500 and 5000ng/L E3, while the male GSI at 5000ng/L E3 was increased and sex reversal was also found at this concentration. Quantitative RT-PCR showed that the hepatic vitellogenin-I (Vtg-I) genes were up-regulated in females at 500 and 5000ng/L E3 and in males at all E3 concentrations, whereas E3 did not affect estrogen receptor α (ERα) mRNA transcription. These results showed that E3 at environmental concentration of 5ng/L has no adverse effects on growth and development of the Japanese medaka. However, in this study, if we only focused on Vtg gene change in males, E3 had strong estrogenic effects on male medaka under the conditions of these experiments. Copyright © 2013 Elsevier Inc. All rights reserved.

  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, Pcannabis resin. Linear regression models were used to study the trends in THC of the different cannabis products over time. A marginal, but significant (Pcannabis 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) content of the most popular herbal cannabis products in the Netherlands has decreased slightly since 2005. The popular

  18. 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

  19. 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

  20. Optimisation of the antifungal potency of the amidated peptide H-Orn-Orn-Trp-Trp-NH2 against food contaminants.

    Science.gov (United States)

    Thery, Thibaut; O'Callaghan, Yvonne; O'Brien, Nora; Arendt, Elke K

    2018-01-16

    The design of novel efficient antimicrobial peptides (AMPs) faces several issues, such as cost of synthesis, proteolytic stability or cytotoxicity. The identification of key determinants involved in the activity of AMPs, such as cationicity and amphipathicity, allowed the synthesis of short peptides with optimized properties. An ultrashort peptide made of the sequence H-Orn-Orn-Trp-Trp-NH2 (O3TR) showed antifungal activity against several contaminants from food products. This peptide inhibited the growth of the filamentous fungi Fusarium culmorum, Penicillium expansum and Aspergillus niger within a range of concentration of 12.5-50μg/ml. In addition, O3TR inhibited the growth of the yeast Saccharomyces cerevisiae, Zygosaccharomyces bailii, Zygosaccharomyces rouxii, Debaryomyces hansenii and Kluyveromyces lactis within the range 12.5-50μg/ml. A derivative peptide, called C12O3TR, made by the addition of lauric acid at the N-terminus of O3TR was 2- to 8-fold more active than O3TR against every species. In addition to the inhibition of conidial germination, O3TR and C12O3TR killed F. culmorum hyphae at 100 and 50μg/ml respectively. The MIC of the two peptides against F. culmorum and Z. bailii after heat treatment at 100°C for 60 min and within the pH range 3-10, were not changed. However, the activity of O3TR against F.culmorum and Z. bailii was strongly reduced in salt solutions, whereas the lauric acid peptide kept its antifungal activity and resistance to proteolytic digestion. The conjugation with lauric acid reduced the random coiled structure and increased the α-helical content of O3TR. After conjugation with the dye tetramethylrhodamine (TMR), both peptides entered F. culmorum spores. They also both induced permeabilization of F. culmorum hyphae but only C12O3TR permeabilized Z. bailii membrane. In contrast to the lipopeptide, O3TR did not show haemolytic or cytotoxic activity when applied at the concentrations that exhibited antifungal potency. The two

  1. 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

    in B16F10 and primary human keratinocyte cells. Our results indicate that hawthorn could be considered as a promising agent for the treatment of melanoma as it shows antitumor activity in vitro and in vivo. Moreover, hawthorn constituents are shown to be highly effective at inhibiting tyrosinase-mediated melanogenesis in vitro on melanoma cells by preventing oxidation in these cells and without affecting the viability of normal human keratinocyte cells. Then, hawthorn might also be used as a new candidate of natural skin depigmenting agents in skin care products.

  2. First-line treatment of pemphigus vulgaris with a combination of rituximab and high-potency topical corticosteroids.

    Science.gov (United States)

    Ingen-Housz-Oro, Saskia; Valeyrie-Allanore, Laurence; Cosnes, Anne; Ortonne, Nicolas; Hüe, Sophie; Paul, Muriel; Wolkenstein, Pierre; Chosidow, Olivier

    2015-02-01

    The main component of the first-line treatment of pemphigus vulgaris is high doses of systemic corticosteroids, but adverse effects of these drugs are frequent and sometimes severe. Rituximab has shown effectiveness as a corticosteroid-sparing agent or in case of relapse. To our knowledge, the effectiveness of rituximab as a first-line treatment without systemic corticosteroids has not been evaluated. Five women in their 50s, 60s, or 70s with pemphigus vulgaris (Pemphigus Disease Area Index score, 15-84 at diagnosis) and contraindications to systemic corticosteroid treatment received rituximab with high-potency topical corticosteroids as first-line treatment. All patients experienced a favorable response, with a mean time to healing of skin and mucosal lesions of 15 weeks. Two patients, with 42- and 48-month follow-up evaluations, did not experience relapse. Three patients developed 2 to 4 relapses, with effective retreatment achieved using rituximab and topical corticosteroids. No severe adverse effects were observed. Considering the high rate of severe adverse effects induced by prolonged administration of high doses of systemic corticosteroids, new therapeutic options are warranted in the treatment of pemphigus vulgaris. The combination of rituximab and topical corticosteroids could be considered in mild to severe cutaneous disease. Larger long-term studies are needed to evaluate the optimal treatment strategies according to the severity of the disease and the benefit-risk ratio of rituximab.

  3. Effect of the Contents and Form of Rabies Glycoprotein on the Potency of Rabies Vaccination in Cattle

    Directory of Open Access Journals (Sweden)

    Piza AT

    2002-01-01

    Full Text Available One of the methods used for controlling cattle rabies in Brazil consists of vaccination. Sometimes, however, rabies occurs in cattle supposedly protected. Since rabies vaccine batches are officially controlled by tests performed on laboratory animals, it is questionable whether the minimal mandatory requirements really correspond to immunogenicity in the target species. We have analyzed the association among potencies of rabies vaccines tested by the NIH test, the contents and form (free-soluble or virus-attached of rabies glycoprotein (G in the vaccine batches, and the virus-neutralizing antibodies (VNA titers elicited in cattle. No correlation was found between G contents in the vaccine batches and the NIH values, whatever the presentation of G. There was no correlation either between NIH values and VNA titers elicited in cattle. There was, however, a positive correlation (r = 0.8681; p = 0.0001 between the amounts of virion-attached G present in the vaccine batches and VNA elicited in cattle. This was not observed when the same analysis was performed with total-glycoprotein or free-soluble glycoprotein. The study demonstrated that NIH values can not predict the effect of the immunogen in cattle. On the other hand, the quantification of virus-attached rabies glycoprotein has a strong correlation with VNA elicited in cattle.

  4. Neurocognitive function and schizophrenia-proneness in individuals dependent on ketamine, on high potency cannabis ('skunk') or on cocaine.

    Science.gov (United States)

    Morgan, C J A; Duffin, S; Hunt, S; Monaghan, L; Mason, O; Curran, H V

    2012-11-01

    Ketamine, psychostimulants and cannabis have all been associated with psychotic phenomena but no study has directly compared users of these drugs. The aim of this study was to assess schizophrenia proneness and neurocognitive function in individuals dependent upon ketamine, cannabis and cocaine. 130 volunteers - 29 'skunk' users, 22 cocaine users, 21 ketamine users, along with 28 'recreational' poly-drug users and 30 drug-naïve controls - were assessed on the Schizophrenia Proneness Instrument, Adult version (SPI-A). They were specifically asked to rate symptoms when not under the acute influence of a psychoactive drug. Ketamine and skunk users manifested the greatest attentional and cognitive disturbances. The symptom profile of the dependent ketamine users was very similar to that of prodromal individuals who transitioned to psychosis. Given the recent rapid rise in use of high potency cannabis and of ketamine, these findings are important and clinicians should be careful to rule out the effects of persistent drug use, especially in users of ketamine or skunk, when assessing an individual's risk of psychosis. A longitudinal study is needed to differentiate which basic symptoms persist following abstention from ketamine and skunk. © Georg Thieme Verlag KG Stuttgart · New York.

  5. 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

  6. Azure B, a metabolite of methylene blue, is a high-potency, reversible inhibitor of monoamine oxidase.

    Science.gov (United States)

    Petzer, Anél; Harvey, Brian H; Wegener, Gregers; Petzer, Jacobus P

    2012-02-01

    Methylene blue (MB) has been shown to act at multiple cellular and molecular targets and as a result possesses diverse medical applications. Among these is a high potency reversible inhibition of monoamine oxidase A (MAO-A) that may, at least in part, underlie its adverse effects but also its psycho- and neuromodulatory actions. MB is metabolized to yield N-demethylated products of which azure B, the monodemethyl species, is the major metabolite. Similar to MB, azure B also displays a variety of biological activities and may therefore contribute to the pharmacological profile of MB. Based on these observations, the present study examines the interactions of azure B with recombinant human MAO-A and -B. The results show that azure B is a potent MAO-A inhibitor (IC₅₀=11 nM), approximately 6-fold more potent than is MB (IC₅₀=70 nM) under identical conditions. Measurements of the time-dependency of inhibition suggest that the interaction of azure B with MAO-A is reversible. Azure B also reversibly inhibits the MAO-B isozyme with an IC₅₀ value of 968 nM. These results suggest that azure B may be a hitherto under recognized contributor to the pharmacology and toxicology of MB by blocking central and peripheral MAO-A activity and as such needs to be considered during its use in humans and animals. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. 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.

  8. What determines skin sensitization potency: Myths, maybes and realities. The 500 molecular weight cut-off: An updated analysis.

    Science.gov (United States)

    Fitzpatrick, Jeremy M; Roberts, David W; Patlewicz, Grace

    2017-01-01

    It is widely accepted that substances must have a molecular weight (MW) system and identified that of the 13 substances with a MW > 500, five were sensitizers. This provided good evidence to refute such a MW 500 threshold. While Roberts et al. (2012) made a convincing case that the MW > 500 cut-off was not a true requirement for sensitization, the number of counter examples identified were too few to draw any statistical conclusions. This updated analysis systematically interrogated a large repository of sensitization information collected under the EU REACH regulation. A data set of 2904 substances that had been tested for skin sensitization, using guinea pigs and/or mice were collected. The data set contained 197 substances with a MW > 500; 33 of these were skin sensitizers. Metal containing complexes, reaction products and mixtures were excluded from further consideration. The final set of 14 sensitizers substantiated the original findings. The study also assessed whether the same reaction chemistry principles established for low MW sensitizers applied to chemicals with a MW > 500. The existing reaction chemistry considerations were found appropriate to rationalize the sensitization behaviour of the 14 sensitizers with a MW > 500. The existence of the MW 500 threshold, based on the widespread misconception that the ability to penetrate efficiently the stratum corneum is a key determinant of skin sensitization potential and potency, was refuted. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  9. A newly described scorpion species, Leiurus abdullahbayrami (Scorpion: Buthidae, and the lethal potency and in vivo effects of its venom

    Directory of Open Access Journals (Sweden)

    O Ozkan

    2011-01-01

    Full Text Available Currently, medically significant scorpion species belong to the Buthidae family and are represented by the genera Androctonus, Buthus, Mesobuthus, Hottentotta, Parabuthus, Tityus, Centruroides, Leiurus. Although Leiurus was originally considered a monotypic genus, four additional species have since been described. Leiurus abdullahbayrami (previously identified as L. quinquestriatus in Turkey was classified as a new Leiurus species. This is the first report conducted on the lethality and biologic effects of L. abdullahbayrami scorpion venom in mice. In this study, the electrophoretic protein pattern of its venom was also determined. Two protein bands with molecular masses of 4 and 6 kDa were more strongly detected than other protein bands in the venom sample. Electrophoresis showed that L. abdullahbayrami scorpion venom possesses both short- and long-chain neurotoxins. The median lethal dose of this venom was found to be 0.19 mg/kg by subcutaneous (SC injection in mice. Animals experimentally envenomed with L. abdullahbayrami venom exhibited hyperexcitability, agitation, aggressive behavior, squeaking and fighting, tachypnea, weakness, convulsions, and death due to cardiac and respiratory failure. In further studies, the potency of antivenom should be investigated in relation to the scorpion venom. Molecular and pharmacological studies are also required to identify and characterize L. abdullahbayrami scorpion venom.

  10. Potency of fiber rumen bacterial isolates from local buffalo inoculated into Frisian Holstein calves during preweaning period

    Directory of Open Access Journals (Sweden)

    Iwan Prihantoro

    2012-12-01

    Full Text Available Fiber-digesting bacteria are the main rumen bacteria that play an important role in digesting feed. These bacteria are adapted to low quality forage from agricultural byproduct. The aim of these study was to determine the potency of fiber-digesting bacteria consortium obtained from buffalo rumen inoculated to Frisian Holstein calves during preweaning on feed consumption, utilization, mineral uptake and physiological status. This study used 14 isolates of bacteria obtained from collection of Faculty of Animal Science, Bogor Agricultural University. The experimental unit consisted of six Frisian Holstein calves at two week old with the average body weight of 38.00 ± 6.23 kg. Calves were inoculated by 20 ml of fiber-digesting rumen bacterial isolates [4.56 x 109 cfu/ml] every morning for four weeks. Experimental design used was based on a completly randomized design with three calves received the respective inoculation (treatment group and three calves without any inoculation (control group. Data were analyzed statistically using t-test method with α = 0.05 and 0.01. The results showed that fiber-digesting bacteria (FDB from rumen buffalo have adapted in the calves rumen since preweaning periode. Inoculation FDB increased the number of rumen bacteria, digestibility of protein and P uptake calves at eight weeks old. Increased feed intake, uptake of Mg and cobalt calves at 14 weeks old. Without causing any negative effects on ADG, physiological status and rumen fermentability.

  11. 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.

  12. Diphenyl ether non-nucleoside reverse transcriptase inhibitors with excellent potency against resistant mutant viruses and promising pharmacokinetic properties.

    Science.gov (United States)

    Sweeney, Zachary K; Kennedy-Smith, Joshua J; Wu, Jeffrey; Arora, Nidhi; Billedeau, J Roland; Davidson, James P; Fretland, Jennifer; Hang, Julie Q; Heilek, Gabrielle M; Harris, Seth F; Hirschfeld, Donald; Inbar, Petra; Javanbakht, Hassan; Jernelius, Jesper A; Jin, Qingwu; Li, Yu; Liang, Weiling; Roetz, Ralf; Sarma, Keshab; Smith, Mark; Stefanidis, Dimitrio; Su, Guoping; Suh, Judy M; Villaseñor, Armando G; Welch, Michael; Zhang, Fang-Jie; Klumpp, Klaus

    2009-01-01

    Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are part of the preferred treatment regimens for individuals infected with HIV. These NNRTI-based regimens are efficacious, but the most popular NNRTIs have a low genetic barrier to resistance and have been associated with adverse events. There is therefore still a need for efficacious antiviral medicines that facilitate patient adherence and allow durable suppression of viral replication. As part of an extensive program targeted toward the discovery of NNRTIs that have favorable pharmacokinetic properties, good potency against NNRTI-resistant viruses, and a high genetic barrier to drug resistance, we focused on the optimization of a series of diaryl ether NNRTIs. In the course of this effort, we employed molecular modeling to design a new set of NNRTIs that that are active against wild-type HIV and key NNRTI-resistant mutant viruses. The structure-activity relationships observed in this series of compounds provide insight into the structural features required for NNRTIs that inhibit the replication of a wide range of mutant viruses. Selected compounds have promising pharmacokinetic profiles.

  13. 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.

  14. 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

  15. 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.

  16. Evaluation of phenolic content and antioxidant potency in various parts of Cassia auriculata L.: a traditionally valued plant.

    Science.gov (United States)

    Purushotham, K N; Annegowda, H V; Sathish, N K; Ramesh, B; Mansor, S M

    2014-01-01

    Presence of polyphenolic content in various part of the plant exhibit wide pharmacological activities including antioxidant activity. The present study was designed to evaluate the phenolic contents (total phenols, flavonoid and tannins) and antioxidant properties of ethanolic extracts of flower, leaf, pod, bark and root obtained from Cassia auriculata. Ethanolic extracts of various parts of C. auriculata obtained by sonication extraction techniques are studied for their phenolic contents and DPPH (2,2-diphenyl-1-picrylhydrazine) radical scavenging assay as well as total antioxidant assays using UV visible spectrophotometer. Among the various parts of the plant studied, bark showed significant content of phenolics, flavonoids and tannins followed by the root, leaf, flower and pod. Even bark extract exhibited highest antioxidant capacity in DPPH assay followed by root, leaf, flower and pod with a value of 766.7, 679.3, 644.9, 572.5 and 474.7 mg vitamin C equivalent antioxidant capacity (mg VCEAC)/sample, respectively. In addition, mg VCEAC values obtained from the total antioxidant assay was in the increasing order of bark > root > leaf > flower > pod. Moreover, a strong correlation was also found between phenolic contents and antioxidant values indicating their influence in the found antioxidant activity, hence the bark extract can be employed as an ideal candidate for herbal based pharmaceutical product. Results of the present study also emphasize variation in the chemical composition as well as biological activity ensuring the importance of proper selection of particular part of the plant to evaluate their therapeutic potency.

  17. Classification of HIV protease inhibitors on the basis of their antiviral potency using radial basis function neural networks

    Science.gov (United States)

    Patankar, S. J.; Jurs, P. C.

    2003-02-01

    HIV protease inhibitors are being used as frontline therapy in the treatment of HIV patients. Multi-drug-resistant HIV mutant strains are emerging with the initial aggressive multi-drug treatment of HIV patients. This necessitates continued search for novel inhibitors of viral replication. These protease inhibitors may further be useful as pharmacological agents for inhibition of other viral replication. Classification models of HIV Protease inhibitors are developed using a data set of 123 compounds containing several heterocycles. Their inhibitory concentrations expressed as log (IC50) ranged from -1.52 to 2.12 log units. The dataset was divided into active and inactive classes on the basis of their antiviral potency. Initially a two-class problem (active, inactive) is explored using k-nearest neighbor approach. In order to introduce non-linearity in the classifier different approaches were investigated. This led to the goal of a fast, simple, minimum user input, radial basis function neural network (RBFNN) classifier development. Then the same two-class problem was resolved using the (RBFNN) classifier. A genetic algorithm with RBFNN fitness evaluator was used to search for the optimum descriptor subsets. The application of majority rules was also tested for the RBFNN classification. The best six descriptor model found by the new cost function showed predictive ability in the high 80% range for an external prediction set.

  18. Comparative potency of subtilisin-cleaved and intact human growth hormone measured in growth hormone-deficient human subjects.

    Science.gov (United States)

    Bunner, D L; Lewis, U J; Vanderlaan, W P

    1979-02-01

    Eight GH-deficient subjects received both subtilisin-cleaved human GH (hGH-S) and intact hGH (hGH-I) during short term balance studies to compare the potency of these two forms of GH. Both forms caused nitrogen retention, calciuria, postassium retention, and elevation of blood glucose. The effects on plasma insulin concentrations were inconstant at the doses used. hGH-S was more potent than hGH-I, as measured by nitrogen and potassium retention, and the differences reached levels of statistical significance. hGH-S also caused greater calciuria and increases in fasting the postprandial blood glucose and in postprandial insulin in absolute terms, but these differences did not reach levels of statistical significance. In no instance was hGH-I significantly more potent than hGH-S. We conclude hGH-S, a two-chain form of hGH, caused significantly greater nitrogen and potassium retention in human subjects in short term balance studies than hGH-I.

  19. How does real affect affect affect recognition in speech?

    NARCIS (Netherlands)

    Truong, Khiet Phuong

    2009-01-01

    The automatic analysis of affect is a relatively new and challenging multidisciplinary research area that has gained a lot of interest over the past few years. The research and development of affect recognition systems has opened many opportunities for improving the interaction between man and

  20. Inhibition of P-glycoprotein-mediated Multidrug Resistance (MDR) by N,N-bis(cyclohexanol)amine aryl esters: further restriction of molecular flexibility maintains high potency and efficacy.

    Science.gov (United States)

    Martelli, Cecilia; Dei, Silvia; Lambert, Catherine; Manetti, Dina; Orlandi, Francesca; Romanelli, Maria Novella; Scapecchi, Serena; Salerno, Milena; Teodori, Elisabetta

    2011-01-01

    Conformational modulation of the aryl portion of a set of N,N-bis(cyclohexanol)amine aryl esters (1a-d) that are potent Pgp-dependent MDR inhibitors has been performed. Toward this end the trans-3-(3,4,5-trimethoxyphenyl)acrylic acid present in set 1 was substituted with 3-(3,4,5-trimethoxyphenyl)propanoic and 3-(3,4,5-trimethoxyphenyl)propiolic moieties to give sets 2 and 3, respectively. While the introduction of 3-(3,4,5-trimethoxyphenyl)propanoic moiety resulted in a definite drop in potency and efficacy, esterification with 3-(3,4,5-trimethoxyphenyl)propiolic acid gave four isomers (3a-d) that maintain high potency and possess optimal efficacy. These results are discussed in terms of conformational flexibility of the different sets of compounds. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. Predictive Modeling of Two-Year Potency Outcomes via a Novel 90-Day Percent 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) following robot-assisted radical prostatectomy as a qualitative adjunct to the IIEF-5 and as a 90-day predictor of two-year potency outcomes. Prospective data was collected from 540 men with preoperative IIEF-5 22-25 who underwent RARP by a single surgeon, of which 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), patients were asked to "indicate the fullness you are able to achieve in erections compared to before surgery?" (0-10…100%). The primary outcome was prediction of potency (defined as ESI) at 24 months, based on 90-day % fullness (0-24%, 25-74%, and 75-100%). 299 men with complete follow-up were included. Significant predictors of 24 month potency included age, BMI, pathologic stage, nerve-sparing status, and % fullness tertiles. When men (pre-op IIEF-5 22-25) were assessed at 90 days post-RARP, 181/299 (61%) men had erections inadequate for intercourse. If IIEF-5 scores 1-6 is used, 142/181 (78%) would be targeted for early intervention. In distinction, if 0-24% fullness is used, 88/181 (49%) are targeted. If both the IIEF-5 and % fullness are used, this is reduced to 77/181 (43%). We introduce % fullness as a qualitative adjunct to the IIEF-5 and separately as a 90-day predictor of two-year potency recovery. This initial report is hypothesis-generating such that the use of % fullness enables the identification of men most likely to benefit from early, secondary intervention. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. A mechanism-based 3D-QSAR approach for classification and prediction of acetylcholinesterase inhibitory potency of organophosphate and carbamate analogs

    Science.gov (United States)

    Lee, Sehan; Barron, Mace G.

    2016-04-01

    Organophosphate (OP) and carbamate esters can inhibit acetylcholinesterase (AChE) by binding covalently to a serine residue in the enzyme active site, and their inhibitory potency depends largely on affinity for the enzyme and the reactivity of the ester. Despite this understanding, there has been no mechanism-based in silico approach for classification and prediction of the inhibitory potency of ether OPs or carbamates. This prompted us to develop a three dimensional prediction framework for OPs, carbamates, and their analogs. Inhibitory structures of a compound that can form the covalent bond were identified through analysis of docked conformations of the compound and its metabolites. Inhibitory potencies of the selected structures were then predicted using a previously developed three dimensional quantitative structure-active relationship. This approach was validated with a large number of structurally diverse OP and carbamate compounds encompassing widely used insecticides and structural analogs including OP flame retardants and thio- and dithiocarbamate pesticides. The modeling revealed that: (1) in addition to classical OP metabolic activation, the toxicity of carbamate compounds can be dependent on biotransformation, (2) OP and carbamate analogs such as OP flame retardants and thiocarbamate herbicides can act as AChEI, (3) hydrogen bonds at the oxyanion hole is critical for AChE inhibition through the covalent bond, and (4) π-π interaction with Trp86 is necessary for strong inhibition of AChE. Our combined computation approach provided detailed understanding of the mechanism of action of OP and carbamate compounds and may be useful for screening a diversity of chemical structures for AChE inhibitory potency.

  3. Recombinant HA1 produced in E. coli forms functional oligomers and generates strain-specific SRID potency antibodies for pandemic influenza vaccines.

    Science.gov (United States)

    Khurana, Surender; Larkin, Christopher; Verma, Swati; Joshi, Manju B; Fontana, Juan; Steven, Alasdair C; King, Lisa R; Manischewitz, Jody; McCormick, William; Gupta, Rajesh K; Golding, Hana

    2011-08-05

    Vaccine production and initiation of mass vaccination is a key factor in rapid response to new influenza pandemic. During the 2009-2010 H1N1 pandemic, several bottlenecks were identified, including the delayed availability of vaccine potency reagents. Currently, antisera for the single-radial immunodiffusion (SRID) potency assay are generated in sheep immunized repeatedly with HA released and purified after bromelain-treatment of influenza virus grown in eggs. This approach was a major bottleneck for pandemic H1N1 (H1N1pdm09) potency reagent development in 2009. Alternative approaches are needed to make HA immunogens for generation of SRID reagents in the shortest possible time. In this study, we found that properly folded recombinant HA1 globular domain (rHA1) from several type A viruses including H1N1pdm09 and two H5N1 viruses could be produced efficiently using a bacterial expression system and subsequent purification. The rHA1 proteins were shown to form functional oligomers of trimers, similar to virus derived HA, and elicited high titer of neutralizing antibodies in rabbits and sheep. Importantly, the immune sera formed precipitation rings with reference antigens in the SRID assay in a dose-dependent manner. The HA contents in multiple H1N1 vaccine products from different manufacturers (and in several lots) as determined with the rHA1-generated sheep sera were similar to the values obtained with a traditionally generated sheep serum from NIBSC. We conclude that bacterially expressed recombinant HA1 proteins can be produced rapidly and used to generate SRID potency reagents shortly after new influenza strains with pandemic potential are identified. Published by Elsevier Ltd.

  4. Potency of a human monoclonal antibody to diphtheria toxin relative to equine diphtheria anti-toxin in a guinea pig intoxication model.

    Science.gov (United States)

    Smith, Heidi L; Cheslock, Peter; Leney, Mark; Barton, Bruce; Molrine, Deborah C

    2016-08-17

    Prompt administration of anti-toxin reduces mortality following Corynebacterium diphtheriae infection. Current treatment relies upon equine diphtheria anti-toxin (DAT), with a 10% risk of serum sickness and rarely anaphylaxis. The global DAT supply is extremely limited; most manufacturers have ceased production. S315 is a neutralizing human IgG1 monoclonal antibody to diphtheria toxin that may provide a safe and effective alternative to equine DAT and address critical supply issues. To guide dose selection for IND-enabling pharmacology and toxicology studies, we dose-ranged S315 and DAT in a guinea pig model of diphtheria intoxication based on the NIH Minimum Requirements potency assay. Animals received a single injection of antibody premixed with toxin, were monitored for 30 days, and assigned a numeric score for clinical signs of disease. Animals receiving ≥ 27.5 µg of S315 or ≥ 1.75 IU of DAT survived whereas animals receiving ≤ 22.5 µg of S315 or ≤ 1.25 IU of DAT died, yielding a potency estimate of 17 µg S315/IU DAT (95% CI 16-21) for an endpoint of survival. Because some surviving animals exhibited transient limb weakness, likely a systemic sign of toxicity, DAT and S315 doses required to prevent hind limb paralysis were also determined, yielding a relative potency of 48 µg/IU (95% CI 38-59) for this alternate endpoint. To support advancement of S315 into clinical trials, potency estimates will be used to evaluate the efficacy of S315 versus DAT in an animal model with antibody administration after toxin exposure, more closely modeling anti-toxin therapy in humans.

  5. The variable potency of TiB{sub 2} nucleant particles in the grain refinement of aluminium by Al-Ti-B additions

    Energy Technology Data Exchange (ETDEWEB)

    Quested, T.E.; Greer, A.L. [Cambridge Univ. (United Kingdom). Dept. of Metallurgy and Materials Science; Cooper, P.S. [London and Scandinavian Metallurgical Co. Ltd., Rotherham (United Kingdom)

    2002-07-01

    The development of Al-Ti-B grain-refiners is outlined. The relationships between nucleant particle potency, number and volume efficiencies, and overall refiner performance are explored. The importance of the particle size distribution is illustrated using hypothetical log-normal distributions in a thermal model for grain refinement which uses a free-growth criterion for grain initiation. In this way the degree of optimization of a current commercial refiner is assessed. (orig.)

  6. 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...

  7. Different Inhibitory Potencies of Oseltamivir Carboxylate, Zanamivir, and Several Tannins on Bacterial and Viral Neuraminidases as Assessed in a Cell-Free Fluorescence-Based Enzyme Inhibition Assay.

    Science.gov (United States)

    Quosdorf, Stefanie; Schuetz, Anja; Kolodziej, Herbert

    2017-11-17

    Neuraminidaseis a key enzyme in the life cycle of influenza viruses and is present in some bacterial pathogens. We here assess the inhibitory potency of plant tannins versus clinically used inhibitors on both a viral and a bacterial model neuraminidase by applying the 2'-(4-methylumbelliferyl)-α-d- N -acetylneuraminic acid (MUNANA)-based activity assay. A range of flavan-3-ols, ellagitannins and chemically defined proanthocyanidin fractions was evaluated in comparison to oseltamivir carboxylate and zanamivir for their inhibitory activities against viral influenza A (H1N1) and bacterial Vibrio cholerae neuraminidase (VCNA). Compared to the positive controls, all tested polyphenols displayed a weak inhibition of the viral enzyme but similar or even higher potency on the bacterial neuraminidase. Structure-activity relationship analyses revealed the presence of galloyl groups and the hydroxylation pattern of the flavan skeleton to be crucial for inhibitory activity. The combination of zanamivir and EPs ® 7630 (root extract of Pelargonium sidoides ) showed synergistic inhibitory effects on the bacterial neuraminidase. Co-crystal structures of VCNA with oseltamivir carboxylate and zanamivir provided insight into bacterial versus viral enzyme-inhibitor interactions. The current data clearly indicate that inhibitor potency strongly depends on the biological origin of the enzyme and that results are not readily transferable. The therapeutic relevance of our findings is briefly discussed.

  8. Different Inhibitory Potencies of Oseltamivir Carboxylate, Zanamivir, and Several Tannins on Bacterial and Viral Neuraminidases as Assessed in a Cell-Free Fluorescence-Based Enzyme Inhibition Assay

    Directory of Open Access Journals (Sweden)

    Stefanie Quosdorf

    2017-11-01

    Full Text Available Neuraminidase is a key enzyme in the life cycle of influenza viruses and is present in some bacterial pathogens. We here assess the inhibitory potency of plant tannins versus clinically used inhibitors on both a viral and a bacterial model neuraminidase by applying the 2′-(4-methylumbelliferyl-α-d-N-acetylneuraminic acid (MUNANA-based activity assay. A range of flavan-3-ols, ellagitannins and chemically defined proanthocyanidin fractions was evaluated in comparison to oseltamivir carboxylate and zanamivir for their inhibitory activities against viral influenza A (H1N1 and bacterial Vibrio cholerae neuraminidase (VCNA. Compared to the positive controls, all tested polyphenols displayed a weak inhibition of the viral enzyme but similar or even higher potency on the bacterial neuraminidase. Structure–activity relationship analyses revealed the presence of galloyl groups and the hydroxylation pattern of the flavan skeleton to be crucial for inhibitory activity. The combination of zanamivir and EPs® 7630 (root extract of Pelargonium sidoides showed synergistic inhibitory effects on the bacterial neuraminidase. Co-crystal structures of VCNA with oseltamivir carboxylate and zanamivir provided insight into bacterial versus viral enzyme-inhibitor interactions. The current data clearly indicate that inhibitor potency strongly depends on the biological origin of the enzyme and that results are not readily transferable. The therapeutic relevance of our findings is briefly discussed.

  9. The antioxidant potency of Punica granatum L. Fruit peel reduces cell proliferation and induces apoptosis on breast cancer.

    Science.gov (United States)

    Dikmen, Miris; Ozturk, Nilgün; Ozturk, Yusuf

    2011-12-01

    Pomegranate (Punica granatum L.) is known to possess pharmacological activities, such as antioxidant and anticancer. In this study, we evaluated the antioxidant potency of a methanolic pomegranate fruit peel extract (PPE) and the relation with its antiproliferative and apoptotic effects on MCF-7 human breast cancer cells. Total phenolic content and antioxidant activity of PPE were determined using the Folin-Ciocalteau and the 2,2-diphenyl-l-picrylhydrazyl free radical methods, respectively. Phenolic acids present in the extract were characterized by a reverse-phase high-performance liquid chromatography (HPLC) method. Cell proliferation was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay. The apoptotic effects were determined by in situ Tdt-mediated dUTP nick end-labeling assay, and Bax/Bcl-2 mRNA expression levels were measured by reverse transcription-polymerase chain reaction. The extraction yield as a percentage of plant material was 37.97% (wt/wt), and total phenolic content was 331.28 mg of gallic acid equivalents/g of extract. According to HPLC analysis, the most abundant phenolic acid detected in the extract was ellagic acid. MCF-7 cell proliferation decreased depending on PPE concentration (25, 50, 100, 200, and 300 μg/mL) and incubation times (24, 48, and 72 hours). After 48 and 72 hours, the apoptotic cell numbers were significantly increased at 100, 200, and 300 μg/mL PPE concentrations. In addition, expression of the pro-apoptotic gene Bax was increased, and that of the anti-apoptotic gene Bcl-2 was decreased after 200 and 300 μg/mL PPE treatment for 48 and 72 hours. Because PPE reduced cell proliferation and induced apoptosis on MCF-7 cancer cells, we believe that PPE has important antioxidant and apoptotic effects.

  10. Synthesize of zinc nanoparticles using Indonesian velvet bean (Mucuna pruriens) extract and evaluate its potency in lowering catalepsy in mice

    Science.gov (United States)

    Eko Sardjono, Ratnaningsih; Khoerunnisa, Fitri; Musthopa, Iqbal; Khairunisa, Dinar; Astuti Suganda, Putri; Rachmawati, Rahmi

    2018-01-01

    This study aims to synthesize zinc nanoparticles using Indonesian velvet bean (Mucuna pruriens) seed extract and evaluate its potency in lowering catalepsy in mice. The research conducted consist of extraction of M. pruriens seed powder, synthesis of zinc-M. pruriens seed extract nanoparticles (Zn-MPn), characterization of Zn-MPn, and catalepsy test of Zn-MPn. M. pruriens seed powder was extracted by maceration using ethanol-water (1:1) at pH 3 adjusted with citric acid. The Zn-MPn was synthesized by reacting zinc acetate dihydrate (Zn(CH3COO2)2.2H2O) solution with M. pruriens seed extract for 40 min, dispersibility of the reaction was controlled by using sonication and ultrasonic homogenizer. The Zn-MPn obtained was characterized by scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX), transmission electron microscopy (TEM), and Fourier-transform infrared (FTIR). Catalepsy test of Zn-MPn was conducted at doses of 5, 10, 15, 20 and 25 mg/kg body weight. The results of SEM-EDX and TEM analysis showed that the Zn-MPn formed nanoparticles with a particle diameter of 55 nm. Based on FTIR analysis, the absorption band at 464.8 cm-1 was a typical absorption indicated the Zn-O interaction on Zn-MPn. Catalepsy test showed that Zn-MPn on the all five doses were able to lower the catalepsy in mice with the best dose was 10 mg/kg body weight.

  11. Exploiting potency of negative pressure in wound dressing using limited access dressing and suction-assisted dressing

    Directory of Open Access Journals (Sweden)

    Pramod Kumar

    2012-01-01

    Full Text Available Role of negative pressure dressing and moist wound healing are well established in the treatment of both acute and chronic wounds with certain advantages and disadvantages in both the techniques. Both these techniques prevents wound colonization, but the negative pressure dressing method has proved to have a greater potency to remove secretions, prevent wound invasion and eradication established infection. In both these techniques there is no accessibility to wound environment. Limited access dressing (LAD is a moist wound dressing with negative pressure. It provides limited access to the wound through two small ports for both dressers and pathogens. The LAD design has notable advantages like wound isolation that reduces chance of wound colonization and safe disposal of infected materials (important factor to reduce hospital-acquired infections, while avoiding some major disadvantages such as opacity of dressing materials, inaccessible offensive smelling wound environment, and relatively high treatment costs. In LAD a definite intermittent negative pressure regimen is followed. The intermittent negative pressure (cycle of 30 minutes suction and 3 1 / 2 hours rest is effective. Overall, the LAD is a safe and effective alternative to conventional dressing methods. LAD is an excellent research tool for wound healing as frequent/continuous record of wound healing is possible without disturbing the wound healing process. LAD is an effective dressing for limb salvage in cases of acute and chronic complex wounds. Leech effect prevents wound related systematic response syndrome and sepsis. Suction-assisted dressing (SAD is a combination of semiocclusive dressing with negative pressure. It works by removal of fluids by intermittent (like LAD negative pressure and preventing bacterial invasion. SAD is especially advantageous where soakage is less, there is no dead tissue covering the wound (e.g., following skin grafting, superficial skin wounds (e

  12. POTENCY AND EFFICACY TEST OF A VACCINE IN ADDITION WITH ADJUVANT AGAINST KOI HERPESVIRUS IN KOI (Cyprinus carpio

    Directory of Open Access Journals (Sweden)

    Lili Sholichah

    2016-12-01

    Full Text Available Koi Herpesvirus (KHV is a malignant virus infecting the goldfish and koi in all stadia and cause mortality up to 95%. The purpose of this study was to determine the potency and efficacy of inactivated-vaccine in addition with adjuvant against KHV in koi fish. The viral propagation was done using a KF-1 cell line in 25 cm3 flask. The cultured virus was harvested on 12 days post inoculation, and then the harvested virus was inactivated with 0.1% formalin as inactivated-vaccine. Three hundred of test fish (10.38 ± 1.25 g maintained in 126 L of plastic containers with aeration, and fed with pellets twice a day. After 14 days of adaptation, the fish were divided into five treatments (A= vaccine; B= vaccine + Complete Freund’s Adjuvant; C= vaccine + Incomplete Freund’s Adjuvant; K+= positive control, and K-= negative control and each treatment has four replicates. Vaccine was given by injecting intramuscularly of 0.1 mL per fish. All fish were challenged by injecting intramuscularly of 0.1 mL of KHV virus with concentration of 104.58 TCID50/mL after 21 days post vaccination. The results showed that the B treatment had higher (P<0.05 values of hematocrit level, lysozyme activity, and titer of antibody compared with positive control. In addition, the survival of fish in B treatment also had the highest percentages and significantly different compared to other treatments (P<0.05. The conclusion of this research was the application of inactivated KHV vaccine in 0.1% formalin with the addition of Complete Freund’s Adjuvant through the injection dose 0.1 mL fish-1 in 104.58 TCID50/mL capable to enhance the immune responses and raised the optimal protection of KHV antibody in koi fish.

  13. 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.

  14. Azure B, a metabolite of methylene blue, is a high-potency, reversible inhibitor of monoamine oxidase

    International Nuclear Information System (INIS)

    Petzer, Anél; Harvey, Brian H.; Wegener, Gregers; Petzer, Jacobus P.

    2012-01-01

    Methylene blue (MB) has been shown to act at multiple cellular and molecular targets and as a result possesses diverse medical applications. Among these is a high potency reversible inhibition of monoamine oxidase A (MAO-A) that may, at least in part, underlie its adverse effects but also its psycho- and neuromodulatory actions. MB is metabolized to yield N-demethylated products of which azure B, the monodemethyl species, is the major metabolite. Similar to MB, azure B also displays a variety of biological activities and may therefore contribute to the pharmacological profile of MB. Based on these observations, the present study examines the interactions of azure B with recombinant human MAO-A and -B. The results show that azure B is a potent MAO-A inhibitor (IC 50 = 11 nM), approximately 6-fold more potent than is MB (IC 50 = 70 nM) under identical conditions. Measurements of the time-dependency of inhibition suggest that the interaction of azure B with MAO-A is reversible. Azure B also reversibly inhibits the MAO-B isozyme with an IC 50 value of 968 nM. These results suggest that azure B may be a hitherto under recognized contributor to the pharmacology and toxicology of MB by blocking central and peripheral MAO-A activity and as such needs to be considered during its use in humans and animals. Highlights: ► Methylene blue (MB) is a known potent MAO-A inhibitor. ► Azure B, the major metabolite of MB, is more potent as a MAO-A inhibitor. ► Azure B may be a contributor to the CNS pharmacology and toxicology of MB.

  15. Azure B, a metabolite of methylene blue, is a high-potency, reversible inhibitor of monoamine oxidase

    Energy Technology Data Exchange (ETDEWEB)

    Petzer, Anél, E-mail: 12264954@nwu.ac.za [Unit for Drug Research and Development, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom, 2520 (South Africa); Harvey, Brian H. [Division of Pharmacology, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom, 2520 (South Africa); Wegener, Gregers [Centre for Psychiatric Research, Aarhus University Hospital-Risskov, Skovagervej 2, 8240 Risskov (Denmark); Petzer, Jacobus P. [Division of Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom, 2520 (South Africa)

    2012-02-01

    Methylene blue (MB) has been shown to act at multiple cellular and molecular targets and as a result possesses diverse medical applications. Among these is a high potency reversible inhibition of monoamine oxidase A (MAO-A) that may, at least in part, underlie its adverse effects but also its psycho- and neuromodulatory actions. MB is metabolized to yield N-demethylated products of which azure B, the monodemethyl species, is the major metabolite. Similar to MB, azure B also displays a variety of biological activities and may therefore contribute to the pharmacological profile of MB. Based on these observations, the present study examines the interactions of azure B with recombinant human MAO-A and -B. The results show that azure B is a potent MAO-A inhibitor (IC{sub 50} = 11 nM), approximately 6-fold more potent than is MB (IC{sub 50} = 70 nM) under identical conditions. Measurements of the time-dependency of inhibition suggest that the interaction of azure B with MAO-A is reversible. Azure B also reversibly inhibits the MAO-B isozyme with an IC{sub 50} value of 968 nM. These results suggest that azure B may be a hitherto under recognized contributor to the pharmacology and toxicology of MB by blocking central and peripheral MAO-A activity and as such needs to be considered during its use in humans and animals. Highlights: ► Methylene blue (MB) is a known potent MAO-A inhibitor. ► Azure B, the major metabolite of MB, is more potent as a MAO-A inhibitor. ► Azure B may be a contributor to the CNS pharmacology and toxicology of MB.

  16. CS2164, a novel multi-target inhibitor against tumor angiogenesis, mitosis and chronic inflammation with anti-tumor potency.

    Science.gov (United States)

    Zhou, You; Shan, Song; Li, Zhi-Bin; Xin, Li-Jun; Pan, De-Si; Yang, Qian-Jiao; Liu, Ying-Ping; Yue, Xu-Peng; Liu, Xiao-Rong; Gao, Ji-Zhou; Zhang, Jin-Wen; Ning, Zhi-Qiang; Lu, Xian-Ping

    2017-03-01

    Although inhibitors targeting tumor angiogenic pathway have provided improvement for clinical treatment in patients with various solid tumors, the still very limited anti-cancer efficacy and acquired drug resistance demand new agents that may offer better clinical benefits. In the effort to find a small molecule potentially targeting several key pathways for tumor development, we designed, discovered and evaluated a novel multi-kinase inhibitor, CS2164. CS2164 inhibited the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRα and c-Kit), mitosis-related kinase Aurora B and chronic inflammation-related kinase CSF-1R in a high potency manner with the IC 50 at a single-digit nanomolar range. Consequently, CS2164 displayed anti-angiogenic activities through suppression of VEGFR/PDGFR phosphorylation, inhibition of ligand-dependent cell proliferation and capillary tube formation, and prevention of vasculature formation in tumor tissues. CS2164 also showed induction of G2/M cell cycle arrest and suppression of cell proliferation in tumor tissues through the inhibition of Aurora B-mediated H3 phosphorylation. Furthermore, CS2164 demonstrated the inhibitory effect on CSF-1R phosphorylation that led to the suppression of ligand-stimulated monocyte-to-macrophage differentiation and reduced CSF-1R + cells in tumor tissues. The in vivo animal efficacy studies revealed that CS2164 induced remarkable regression or complete inhibition of tumor growth at well-tolerated oral doses in several human tumor xenograft models. Collectively, these results indicate that CS2164 is a highly selective multi-kinase inhibitor with potent anti-tumor activities against tumor angiogenesis, mitosis and chronic inflammation, which may provide the rationale for further clinical assessment of CS2164 as a therapeutic agent in the treatment of cancer. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  17. Estrogenic potency of benzophenone UV filters in breast cancer cells: proliferative and transcriptional activity substantiated by docking analysis.

    Directory of Open Access Journals (Sweden)

    Gwenneg Kerdivel

    Full Text Available The results from recent studies show that some benzophenones (BPs and their hydroxylated metabolites can function as weak estrogens (E2 in the environment. However, little is known about the structure-activity relationship of these molecules. We have examined the effects of exposure to ten different BPs on the proliferation of estrogen receptor (ER-positive breast cancer cells and on the transcriptional activity of E2-target genes. We analyzed two genes that are tightly linked with estrogen-mediated proliferation, the CXCL12 and amphiregulin genes and two classical estrogen-responsive genes, the pS2 and progesterone receptor. Significant differences in the BPs efficiency to induce cell proliferation and endogenous E2-target gene expressions were observed. Using ERE-, Sp1-, AP1- and C3-reporter genes that contain different ER-binding sites in their promoter, we also showed significant differences in the BPs efficiency in activation of the ER transactivation. Together, our analyzes showed that the most active molecule is 4-hydroxy-BP. Docking analysis of the interaction of BPs in the ligand-binding pocket of ERα suggests that the minimum structural requirement for the estrogenic activity of BPs is a hydroxyl (OH group in the phenyl A-ring that allows interaction with Glu-353, Arg-394 or Phe-404, which enhances the stability between BPs and ERα. Our modeling also indicates a loss of interaction between the OH groups of the phenyl B-ring and His-524. In addition, the presence of some OH groups in the phenyl B-ring can create repulsion forces, which may constrain helix 12 in an unfavorable position, explaining the differential estrogenic effects of BPs. These results, together with our analysis of BPs for their potency in activation of cell proliferation and ER-mediated transcription, report an improved understanding of the mechanism and structure-activity relationship of BPs.

  18. 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.

  19. A tool for rapid screening of direct DNA agents using reaction rates and relative interaction potency: towards screening environmental contaminants for hazard.

    Science.gov (United States)

    Gavina, Jennilee M A; Rubab, Mamoona; Zhang, Huijuan; Zhu, Jiping; Nong, Andy; Feng, Yong-Lai

    2011-11-01

    DNA damage represents a potential biomarker for determining the exposure risk to chemicals and may provide early warning data for identifying chemical hazards to human health. Here, we have demonstrated a simple chromatography-based method that can be used to rapidly screen for the presence of chemical hazards as well as to determine parameters relevant to hazard assessment. In this proof-of-principle study, a simple in vitro system was used to determine the interaction of pollutants and probable carcinogens, phenyl glycidyl ether (PGE), tetrachlorohydroquinone (Cl(4)HQ), methylmethane sulfonate (MMS), styrene-7,8-oxide (SO), and benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), a metabolite of benzo[a]pyrene (B[a]P), with single- and double-stranded DNA probes. Differences in potency and reaction kinetics were studied for chemical and DNA type. A relative interaction potency equivalency (PEQ) of a chemical was determined by ratio of interaction potency of a chemical to BPDE as the reference chemical in the reaction with single- and double-stranded oligodeoxynucleotides. PEQs were found to be BPDE > PGE > SO > MMS > Cl(4)HQ for single-stranded oligodeoxynucleotides while they were found to be BPDE > PGE > Cl(4)HQ > MMS > SO for double-stranded oligodeoxynucleotides. Kinetics evaluation revealed that BPDE reacted with both DNA probes at a significantly faster rate, as compared to the remaining test chemicals. Equilibrium was reached within an hour for BPDE, but required a minimum of 48 h for the remaining chemicals. First-order rate constants were (1.61 ± 0.2) × 10(-3) s(-1) and (3.18 ± 0.4) × 10(-4) s(-1) for reaction of BPDE with double- and single-stranded DNA, respectively. The remaining chemicals possessed rate constants from 2 to 13 × 10(-6) s(-1) with a relative kinetic order for reaction with DNA of BPDE ≫ MMS > SO > PGE > Cl(4)HQ for ds-DNA and BPDE ≫ SO ≈ Cl(4)HQ ≈ MMS > PGE for ss-DNA. We further found that the reaction potency, defined by

  20. Stem cells: their source, potency and use in regenerative therapies with focus on adipose-derived stem cells - a review.

    Science.gov (United States)

    Bacakova, Lucie; Zarubova, Jana; Travnickova, Martina; Musilkova, Jana; Pajorova, Julia; Slepicka, Petr; Kasalkova, Nikola Slepickova; Svorcik, Vaclav; Kolska, Zdenka; Motarjemi, Hooman; Molitor, Martin

    2018-03-18

    Stem cells can be defined as units of biological organization that are responsible for the development and the regeneration of organ and tissue systems. They are able to renew their populations and to differentiate into multiple cell lineages. Therefore, these cells have great potential in advanced tissue engineering and cell therapies. When seeded on synthetic or nature-derived scaffolds in vitro, stem cells can be differentiated towards the desired phenotype by an appropriate composition, by an appropriate architecture, and by appropriate physicochemical and mechanical properties of the scaffolds, particularly if the scaffold properties are combined with a suitable composition of cell culture media, and with suitable mechanical, electrical or magnetic stimulation. For cell therapy, stem cells can be injected directly into damaged tissues and organs in vivo. Since the regenerative effect of stem cells is based mainly on the autocrine production of growth factors, immunomodulators and other bioactive molecules stored in extracellular vesicles, these structures can be isolated and used instead of cells for a novel therapeutic approach called "stem cell-based cell-free therapy". There are four main sources of stem cells, i.e. embryonic tissues, fetal tissues, adult tissues and differentiated somatic cells after they have been genetically reprogrammed, which are referred to as induced pluripotent stem cells (iPSCs). Although adult stem cells have lower potency than the other three stem cell types, i.e. they are capable of differentiating into only a limited quantity of specific cell types, these cells are able to overcome the ethical and legal issues accompanying the application of embryonic and fetal stem cells and the mutational effects associated with iPSCs. Moreover, adult stem cells can be used in autogenous form. These cells are present in practically all tissues in the organism. However, adipose tissue seems to be the most advantageous tissue from which to

  1. 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

  2. Potencies of red seabream AHR1- and AHR2-mediated transactivation by dioxins: implication of both AHRs in dioxin toxicity.

    Science.gov (United States)

    Bak, Su-Min; Iida, Midori; Hirano, Masashi; Iwata, Hisato; Kim, Eun-Young

    2013-03-19

    To evaluate species- and isoform-specific responses to dioxins and related compounds (DRCs) via aryl hydrocarbon receptor (AHR) in the red seabream ( Pagrus major ), we constructed a reporter gene assay system. Each expression plasmid of red seabream AHR1 (rsAHR1) and AHR2 (rsAHR2) together with a reporter plasmid containing red seabream CYP1A 5'-flanking region were transfected into COS-7 cells. The cells were treated with graded concentrations of seven DRC congeners including 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD, 1,2,3,4,7,8-HxCDD, 2,3,7,8-TCDF, 2,3,4,7,8-PeCDF, 1,2,3,4,7,8-HxCDF, and PCB126. Both rsAHR1 and rsAHR2 exhibited dose-dependent responses for all the tested congeners. The rsAHR isoform-specific TCDD induction equivalency factors (rsAHR1- and rsAHR2-IEFs) were calculated on the basis of 2,3,7,8-TCDD relative potency derived from the dose-response of each congener. The rsAHR1-IEFs of PeCDD, HxCDD, TCDF, PeCDF, and HxCDF were estimated as 0.17, 0.29, 2.5, 1.5, and 0.27, respectively. For PCB126, no rsAHR1-IEF was given because of less than 10% 2,3,7,8-TCDD maximum response. The rsAHR2-IEFs of PeCDD, HxCDD, TCDF, PeCDF, HxCDF, and PCB126 were estimated as 0.38, 0.13, 1.5, 0.93, 0.20, and 0.0085, respectively. The rsAHR1/2-IEF profiles were different from WHO toxic equivalency factors for fish. In silico docking simulations supported that both rsAHRs have potentials to bind to these congeners. These results suggest that dioxin toxicities may be mediated by both rsAHRs in red seabreams.

  3. Gene-silencing potency of symmetric and asymmetric lipid-conjugated siRNAs and its correlation with dicer recognition.

    Science.gov (United States)

    Kubo, Takanori; Yanagihara, Kazuyoshi; Sato, Yuichiro; Nishimura, Yoshio; Kondo, Shinichi; Seyama, Toshio

    2013-12-18

    Three types of siRNAs and three types of left-overhang siRNAs (LoRNAs) were synthesized along with their conjugations with palmitic acid (C16) to investigate the correlation between Dicer recognition and gene-silencing potency. The siRNA types were composed of 21-nucleotide (nt), 23-nt, and 25-nt lengths of sense and antisense strands with a 2-nt overhang at each 3'-end. The three LoRNA types were composed of a 21-nt, a 23-nt, and a 25-nt length of sense strand with a 2-nt DNA at the 3'-blunt-end and a 23-nt, a 25-nt, and a 27-nt length of antisense strand with a 2-nt overhang at the 3'-end. Additionally, each of these siRNAs and LoRNAs was modified with a C16 at the 5'- or 3'-end of the sense strand; these were named C16-siRNAs and C16-LoRNAs, respectively. The siRNAs and C16-siRNAs were barely cleaved by Dicer, and their gene-silencing efficacies were not excellent, contrary to our expectations. In contrast, most of the LoRNAs and C16-LoRNAs became substrates of Dicer, and they showed both strong gene-silencing efficacies and high nuclease resistance. Among the LoRNAs, the 25D-C16/27-nt LoRNA, which is composed of a 25-nt sense strand with a 2-nt DNA conjugated with C16 at the 3'-end and a 27-nt antisense strand with a 2-nt overhang at the 3'-end, showed an excellent gene-silencing effect with high cell membrane permeability and strong resistance against nuclease degradation. Additionally, the Lo25D-C16/27RNA excelled in all three aspects, nuclease resistance, cell membrane permeability, and RNAi efficacy, compared with the cholesterol conjugation. We are certain that Lo25D-C16/27RNA can be useful as a new generation of RNAi molecules with which to overcome some of the limitations of RNAi technology.

  4. Rapid blockade of telomerase activity and tumor cell growth by the DPL lipofection of ribbon antisense to hTR.

    Science.gov (United States)

    Bajpai, Arun K; Park, Jeong-Hoh; Moon, Ik-Jae; Kang, Hyungu; Lee, Yun-Han; Doh, Kyung-Oh; Suh, Seong-Il; Chang, Byeong-Churl; Park, Jong-Gu

    2005-09-29

    Ribbon antisense (RiAS) to the hTR RNA, a component of the telomerase complex, was employed to inhibit telomerase activity and cancer cell growth. The antisense molecule, hTR-RiAS, combined with enhanced cellular uptake was shown to effectively inhibit telomerase activity and cause rapid cell death in various cancer cell lines. When cancer cells were treated with hTR-RiAS, the level of hTR RNA was reduced by more than 90% accompanied with reduction in telomerase activity. When checked for cancer cell viability, cancer cell lines treated with hTR-RiAS using DNA+Peptide+Lipid complex showed 70-80% growth inhibition in 3 days. The reduced cell viability was due to apoptosis as the percentage of cells exhibiting the sub-G0 arrest and DNA fragmentation increased after antisense treatment. Further, when subcutaneous tumors of a colon cancer cell line (SW480) were treated intratumorally with hTR-RiAS, tumor growth was markedly suppressed with almost total ablation of hTR RNA in the tumor tissue. Cells in the tumor tissue were also found to undergo apoptosis after hTR-RiAS treatment. These results suggest that hTR-RiAS is an effective anticancer reagent, with a potential for broad efficacy to diverse malignant tumors.

  5. Engaging in Affective Practices

    DEFF Research Database (Denmark)

    Galløe, Lotte Rannveig

    schools, the paper develops an affective-power approach drawing on Foucault’s notion of power and Whetherell’s conceptualisation of affect. The approach captures the affective dimension of governing and resistance in interactional practice that engages teachers and pupils. This enables a research focus...

  6. Overexpressing cell systems are a competitive option to primary adipocytes when predicting in vivo potency of dual GPR81/GPR109A agonists.

    Science.gov (United States)

    Almquist, Joachim; Hovdal, Daniel; Ahlström, Christine; Fjellström, Ola; Gennemark, Peter; Sundqvist, Monika

    2018-03-01

    Mathematical models predicting in vivo pharmacodynamic effects from in vitro data can accelerate drug discovery, and reduce costs and animal use. However, data integration and modeling is non-trivial when more than one drug-target receptor is involved in the biological response. We modeled the inhibition of non-esterified fatty acid release by dual G-protein-coupled receptor 81/109A (GPR81/GPR109A) agonists in vivo in the rat, to estimate the in vivo EC 50 values for 12 different compounds. We subsequently predicted those potency estimates using EC 50 values obtained from concentration-response data in isolated primary adipocytes and cell systems overexpressing GPR81 or GPR109A in vitro. A simple linear regression model based on data from primary adipocytes predicted the in vivo EC 50 better than simple linear regression models based on in vitro data from either of the cell systems. Three models combining the data from the overexpressing cell systems were also evaluated: two piecewise linear models defining logical OR- and AND-circuits, and a multivariate linear regression model. All three models performed better than the simple linear regression model based on data from primary adipocytes. The OR-model was favored since it is likely that activation of either GPR81 or GPR109A is sufficient to deactivate the cAMP pathway, and thereby inhibit non-esterified fatty acid release. The OR-model was also able to predict the in vivo selectivity between the two receptors. Finally, the OR-model was used to predict the in vivo potency of 1651 new compounds. This work suggests that data from the overexpressing cell systems are sufficient to predict in vivo potency of GPR81/GPR109A agonists, an approach contributing to faster and leaner drug discovery. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Potency following high-dose three-dimensional conformal radiotherapy and the impact of prior major urologic surgical procedures in patients treated for prostate cancer

    International Nuclear Information System (INIS)

    Chinn, Daniel M.; Holland, John; Crownover, Richard L.; Roach, Mack

    1995-01-01

    Purpose: To assess the impact of high-dose three-dimensional conformal radiotherapy (3DCRT) on potency in patients treated for clinically localized prostate cancer and to identify factors that might predict the outcome of sexual function following treatment. Methods and Materials: One hundred twenty-four consecutive patients treated with 3DCRT for localized prostate cancer at UCSF between 1991-1993 were included in this retrospective analysis. Patient responses were obtained from a mailed questionnaire, telephone interviews, or departmental records. Median follow-up was 21 months. Results: Sixty patients reported having sexual function prior to 3DCRT, including 47 who were fully potent and 13 who were marginally potent. Of the remaining 64 patients, 45 were impotent, 7 were on hormones, 1 was status-postorchiectomy, and 11 were not evaluable. Following 3DCRT, 37 of 60 patients (62%) retained sexual function sufficient for intercourse. Of those with sexual function before irradiation, 33 of 47 (70%) of patients fully potent and 4 of 13 (31%) of patients marginally potent maintained function sufficient for intercourse (p < 0.01). Potency was retained in 6 of 15 (40%) patients with a history of a major urologic surgical procedure (MUSP) and in 31 of 45 (69%) with no history of a MUSP (p < 0.04). Transurethral resection of the prostate was the MUSP in eight of these patients, with four (50%) maintaining sexual function. Conclusions: Patients who receive definitive 3DCRT for localized prostate cancer appear to maintain potency similar to patients treated with conventional radiotherapy. However, patients who are marginally potent at presentation or who have a history of a MUSP appear to be at increased risk of impotence following 3DCRT

  8. The influence of temperature treatment before cryopreservation on the viability and potency of cryopreserved and thawed CD34+and CD45+cord blood cells.

    Science.gov (United States)

    Schwandt, Svenja; Liedtke, Stefanie; Kogler, Gesine

    2017-08-01

    Hematopoietic stem cell (HSC) viability and potency is crucial for qualified cord blood (CB) transplants. This study analyzes time and temperature condition before cryopreservation for the viability of CD34 + /CD45 + cells after cryopreservation. Cell viabilities were determined by antibody co-staining with 7-aminoactinomycin D detecting necrotic cells, and subsequent flow cytometric analysis. Additionally, Annexin V staining for determination of apoptotic cells and colony-forming unit (CFU) assays for testing functional potency of HSCs were performed. For all cell types assessed (CD45 + /CD34 + cells, lymphocytes and granulocytes), the highest viabilities were obtained for CB maintained at 4°C or room temperature (RT; 22 ± 4°C) and cryopreserved directly after collection. Starting material were CB units with an age of 24.7 ± 3.5 h after birth. Post-thaw CD34 + cell results were > 90% after temperature treatment of t = 24 h (48 h total age) and > 70% after t = 48 h (72 h total age) at 4°C (48 h, 91.4 ± 5.5%; 72 h, 75.0 ± 12.0%) and RT (48 h, 84.2 ± 9.7%; 72 h, 72.6 ± 0.6%). Viabilities for 30°C samples were cryopreservation should be minimized because increasing time reduces numbers of viable cells and CFUs before/after cryopreservation. CB units should be maintained at 4°C/RT to retain the highest possible potency of the cells after thawing. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  9. CCR5 Antagonist TD-0680 Uses a Novel Mechanism for Enhanced Potency against HIV-1 Entry, Cell-mediated Infection, and a Resistant Variant*

    Science.gov (United States)

    Kang, Yuanxi; Wu, Zhiwei; Lau, Terrence C. K.; Lu, Xiaofan; Liu, Li; Cheung, Allen K. L.; Tan, Zhiwu; Ng, Jenny; Liang, Jianguo; Wang, Haibo; Li, Saikam; Zheng, Bojian; Li, Ben; Chen, Li; Chen, Zhiwei

    2012-01-01

    Regardless of the route of transmission, R5-tropic HIV-1 predominates early in infection, rendering C-C chemokine receptor type 5 (CCR5) antagonists as attractive agents not only for antiretroviral therapy but also for prevention. Here, we report the specificity, potency, and underlying mechanism of action of a novel small molecule CCR5 antagonist, TD-0680. TD-0680 displayed the greatest potency against a diverse group of R5-tropic HIV-1 and SIV strains when compared with its prodrug, TD-0232, the Food and Drug Administration-approved CCR5 antagonist Maraviroc, and TAK-779, with EC50 values in the subnanomolar range (0.09–2.29 nm). Importantly, TD-0680 was equally potent at blocking envelope-mediated cell-cell fusion and cell-mediated viral transmission as well as the replication of a TAK-779/Maraviroc-resistant HIV-1 variant. Interestingly, TD-0232 and TD-0680 functioned differently despite binding to a similar transmembrane pocket of CCR5. Site-directed mutagenesis, drug combination, and antibody blocking assays identified a novel mechanism of action of TD-0680. In addition to binding to the transmembrane pocket, the unique exo configuration of this molecule protrudes and sterically blocks access to the extracellular loop 2 (ECL2) region of CCR5, thereby interrupting the interaction between virus and its co-receptor more effectively. This mechanism of action was supported by the observations of similar TD-0680 potency against CD4-dependent and -independent SIV strains and by molecular docking analysis using a CCR5 model. TD-0680, therefore, merits development as an anti-HIV-1 agent for therapeutic purposes and/or as a topical microbicide for the prevention of sexual transmission of R5-tropic HIV-1. PMID:22447925

  10. Affectivity and race

    DEFF Research Database (Denmark)

    Vitus, Kathrine; Andreassen, Rikke

    of the Nordic countries, Affectivity and Race draws on a variety of sources, including television programmes, news media, fictional literature, interviews, ethnographic observations, teaching curricula and policy documents, to explore the ways in which ideas about affectivity and emotion afford new insights...... into the experience of racial difference and the unfolding of political discourses on race in various social spheres. Organised around the themes of the politicisation of race through affect, the way that race produces affect and the affective experience of race, this interdisciplinary collection sheds light...

  11. Finding the perfect spot for fluorine: improving potency up to 40-fold during a rational fluorine scan of a Bruton's Tyrosine Kinase (BTK) inhibitor scaffold.

    Science.gov (United States)

    Lou, Yan; Sweeney, Zachary K; Kuglstatter, Andreas; Davis, Dana; Goldstein, David M; Han, Xiaochun; Hong, Junbae; Kocer, Buelent; Kondru, Rama K; Litman, Renee; McIntosh, Joel; Sarma, Keshab; Suh, Judy; Taygerly, Joshua; Owens, Timothy D

    2015-01-15

    A rational fluorine scan based on co-crystal structures was explored to increase the potency of a series of selective BTK inhibitors. While fluorine substitution on a saturated bicyclic ring system yields no apparent benefit, the same operation on an unsaturated bicyclic ring can increase HWB activity by up to 40-fold. Comparison of co-crystal structures of parent molecules and fluorinated counterparts revealed the importance of placing fluorine at the optimal position to achieve favorable interactions with protein side chains. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Study of the effect of thiols on the vasodilatory potency of S-nitrosothiols by using a modified aortic ring assay

    International Nuclear Information System (INIS)

    Giustarini, Daniela; Tsikas, Dimitrios; Rossi, Ranieri

    2011-01-01

    Both low-molecular-mass thiols (LMM-SH) and protein thiols (P-SH) can modulate the biological activity of S-nitrosothiols (RSNO) via S-transnitrosation reactions. It has been difficult to evaluate the entity of this effect in blood circulation by in vitro assays with isolated aorta rings so far, because media rich in proteins cannot be used due to the foaming as a consequence of the needed gas bubbling. We have modified the original apparatus for organ bioassay in order to minimize foaming and to increase analytical performance. By using this modified bioassay we investigated the vasodilatory potency of various endogenous RSNOs in the presence of physiologically relevant concentrations of albumin and LMM-SH. Our results show that the sulfhydryl group of the cysteine moiety of albumin and LMM-SH has a dramatic effect on the vasodilatory potency of RSNO. Considering the equilibrium constants for S-transnitrosation reactions and the concentration of P-SH and LMM-SH we measured in healthy humans (aged 18-85 years), we infer that the age-dependency of hematic levels of LMM-SH may have a considerable impact in RSNO-mediated vasodilation. S-Nitrosoproteins such as S-nitrosoalbumin may constitute a relatively silent and constant amount of circulating RSNO. On the other hand, LMM-SH may mediate and control the biological actions of S-nitrosoproteins via S-transnitrosation reactions, by forming more potent nitric oxide-releasing LMM-S-nitrosothiols. Lifestyle habits, status of health and individual age are proven factors that, in turn, may influence the concentration of these compounds. These aspects should be taken into consideration when testing the vasodilatory effects of RSNO in pre-clinical studies. - Highlights: → A modification of the organ chamber apparatus for aortic ring bioassays is proposed. → The new apparatus can work in the presence of albumin at physiological concentrations. → Potency of RSNOs was studied in the presence of albumin and low molecular

  13. Affectivity and Race

    DEFF Research Database (Denmark)

    of the Nordic countries, Affectivity and Race draws on a variety of sources, including television programmes, news media, fictional literature, interviews, ethnographic observations, teaching curricula and policy documents, to explore the ways in which ideas about affectivity and emotion afford new insights...... into the experience of racial difference and the unfolding of political discourses on race in various social spheres. Organised around the themes of the politicisation of race through affect, the way that race produces affect and the affective experience of race, this interdisciplinary collection sheds light...... on the role of feelings in the formation of subjectivities, how race and whiteness are affectively circulated in public life and the ways in which emotions contribute to regimes of inclusion and exclusion. As such it will appeal to scholars across the social sciences, with interests in sociology, anthropology...

  14. Affectivity and race

    DEFF Research Database (Denmark)

    of the Nordic countries, Affectivity and Race draws on a variety of sources, including television programmes, news media, fictional literature, interviews, ethnographic observations, teaching curricula and policy documents, to explore the ways in which ideas about affectivity and emotion afford new insights...... into the experience of racial difference and the unfolding of political discourses on race in various social spheres. Organised around the themes of the politicisation of race through affect, the way that race produces affect and the affective experience of race, this interdisciplinary collection sheds light...... on the role of feelings in the formation of subjectivities, how race and whiteness are affectively circulated in public life and the ways in which emotions contribute to regimes of inclusion and exclusion. As such it will appeal to scholars across the social sciences, with interests in sociology, anthropology...

  15. 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.

  16. Study of the design and analytical properties of the lethality neutralization assay used to estimate antivenom potency against Bothrops asper snake venom.

    Science.gov (United States)

    Solano, Gabriela; Segura, Alvaro; Herrera, María; Gómez, Aarón; Villalta, Mauren; Gutiérrez, José María; León, Guillermo

    2010-09-01

    The lethality neutralization assay performed in mice is the standard recommended by the World Health Organization to estimate antivenom potency. The interpretation of its results without considering its analytical capacity may lead to erroneous conclusions. Therefore, laboratories that manufacture or control antivenoms must demonstrate the appropriateness of their models. A study of the method used at Instituto Clodomiro Picado, Costa Rica, to estimate the potency of antivenoms against Bothrops asper snake venom was performed. Results show that venom doses ranging from 2 to 6 Median Lethal Doses (LD50) are appropriate to be used as challenge in this test. Variables such as the injection route, number of mice used per venom/antivenom level, and weight of the animals are critical in the estimation of the Median Effective Dose (ED50), whereas incubation time is not. The assay has an acceptable selectivity, linearity, and limits of detection and quantification. Accuracy of the lethality neutralization assay, expressed as percentage recovery, was between 71% and 127%. Intermediate precision, expressed as relative standard deviation, was < or = 17%. It is concluded that the analytical characteristics of this assay are adequate enough to prove product compliance and to have statistical control over an industrial line of antivenom serial production. Copyright 2010 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.

  17. Comparative potencies of contemporary generic vancomycin lot: in vitro assay results from nine products and a reference reagent-grade sample.

    Science.gov (United States)

    Jones, Ronald N; Watters, Amy A; Flamm, Robert K; Sader, Helio S

    2013-06-01

    Numerous studies of generic vancomycin (GV) lots have emerged since the 1980s, casting some doubt on product quality. Publications question the in vivo activity, even when concurrent in vitro and chemical assays meet regulatory guidelines. This study assessed contemporary GV lots by an in vitro assay capable of measuring small variations from target-benchmark (BM) activity. Nine GV lots (Hospira [6 lots; 0.5- or 1.0-g vials], Akorn [1 lot; 1.0-g vial], APP [2 lots; 1.0-g vials]) were obtained from local United States distributors. A reagent-grade lot (Sigma lot 080M1341V) was tested as BM component due to the inability to purchase branded product vials in the USA. All lots of GV did not vary significantly from the analytical control when testing the 3 Staphylococcus aureus (wild-type 4B25, ATCC 25923, and 29213) and Enterococcus faecalis (ATCC 29212) strains. These MIC end points were read at 18 h of incubation, and Hospira lots averaged +3.5% potency (range, -3% to +8%), and Akorn and APP at 0% variance, e.g., acceptable performance. In conclusion, with a validated, precise multi-organism assay, current GV lots marketed in the USA showed minimal activity variations from a selected BM control lot. Generic antimicrobial products, in general, should be regularly monitored for potency, chemical purity, and in vivo activity before routine use in medical centers. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Structure-Based Design of an Organoruthenium Phosphatidyl-inositol-3-Kinase Inhibitor Reveals a Switch Governing Lipid Kinase Potency and Selectivity

    Energy Technology Data Exchange (ETDEWEB)

    Xie,P.; Williams, D.; Atilla-Gokcumen, G.; Milk, L.; Xiao, M.; Smalley, K.; Herlyn, M.; Meggers, E.; Marmorstein, R.

    2008-01-01

    Mutations that constitutively activate the phosphatidyl-inositol-3-kinase (PI3K) signaling pathway, including alterations in PI3K, PTEN, and AKT, are found in a variety of human cancers, implicating the PI3K lipid kinase as an attractive target for the development of therapeutic agents to treat cancer and other related diseases. In this study, we report on the combination of a novel organometallic kinase inhibitor scaffold with structure-based design to develop a PI3K inhibitor, called E5E2, with an IC50 potency in the mid-low-nanomolar range and selectivity against a panel of protein kinases. We also show that E5E2 inhibits phospho-AKT in human melanoma cells and leads to growth inhibition. Consistent with a role for the PI3K pathway in tumor cell invasion, E5E2 treatment also inhibits the migration of melanoma cells in a 3D spheroid assay. The structure of the PI3K?/E5E2 complex reveals the molecular features that give rise to this potency and selectivity toward lipid kinases with implications for the design of a subsequent generation of PI3K-isoform-specific organometallic inhibitors.

  19. 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.

  20. Introducing metallocene into a triazole peptide conjugate reduces its off-rate and enhances its affinity and antiviral potency for HIV-1 gp120

    Science.gov (United States)

    Gopi, Hosahudya; Cocklin, Simon; Pirrone, Vanessa; McFadden, Karyn; Tuzer, Ferit; Zentner, Isaac; Ajith, Sandya; Baxter, Sabine; Jawanda, Navneet; Krebs, Fred C.; Chaiken, Irwin M.

    2013-01-01

    In this work, we identified a high affinity and potency metallocene-containing triazole peptide conjugate that suppresses the interactions of HIV-1 envelope gp120 at both its CD4 and co-receptor binding sites. The ferrocene-peptide conjugate, HNG-156, was formed by an on-resin copper-catalysed [2 + 3] cycloaddition reaction. Surface plasmon resonance interaction analysis revealed that, compared to a previously reported phenyl-containing triazole conjugate HNG-105 (105), peptide 156 had a higher direct binding affinity for several subtypes of HIV-1 gp120 due mainly to the decreased dissociation rate of the conjugate-gp120 complex. The ferrocene triazole conjugate bound to gp120 of both clade A (92UG037-08) and clade B (YU-2 and SF162) virus subtypes with nanomolar KD in direct binding and inhibited the binding of gp120 to soluble CD4 and to antibodies that bind to HIV-1YU-2 gp120 at both the CD4 binding site and CD4-induced binding sites. HNG-156 showed a close-to nanomolar IC50 for inhibiting cell infection by HIV-1BaL whole virus. The dual receptor site antagonist activity and potency of HNG-156 make it a promising viral envelope inhibitor lead for developing anti-HIV-1 treatments. PMID:18498083

  1. Ekotūrisma attīstīšanas potenciāls Zebrus-Īles mežu masīvā

    OpenAIRE

    Bērziņa, Anete

    2014-01-01

    Maģistra darbs „Ekotūrisma attīstīšanas potenciāls Zebrus-Īles mežu masīvā” izstrādāts ar mērķi novērtēt Zebrus-Īles mežu masīva piemērotību ekotūrisma specializācijai. Pētījuma būtība ir novērtēt, vai pētījuma teritorijai ir potenciāls attīstīt ekotūrismu, ņemot vērā tās ekotūrisma resursus un vietējo iedzīvotāju attieksmi. Galvenie rezultāti norāda uz vides gida lielo nozīmi ekotūrisma organizēšanā un nepieciešamajām zināšanām par vietu un prasmi to nodot citiem. Kopumā iedzīvotāji atbalsta...

  2. Affects and assemblages

    DEFF Research Database (Denmark)

    Samson, Kristine

    Affects and assemblages are Deleuzian Guattarian notions related to aesthetics and spatial territories. In recent urban geography and urban studies these notions are increasingly gaining more impact (Amin & Thrift 2002, Pile 2008, Farías & Bender 2010, Andersen & Harrison 2010, Thrift 2008). What...... happens to aesthetics and how does it change the existing social and geographical understanding of urban space? The paper sets out to reintroduce aesthetical aspects of affects and assemblages in relation to urban space and urban planning. It presupposes urban space as a continuous state of becoming where...... affects and assemblages produce subjective feelings and emotions (Pile 2009) Recently, urban experience designs and events aim at evoking affects through affects and assemblages. A Danish example is the Carlsberg city in Copenhagen another is The High line in Chelsea, New York (Samson 2011). Thus...

  3. Affectivity and race

    DEFF Research Database (Denmark)

    This book presents new empirical studies of social difference in the Nordic welfare states, in order to advance novel theoretical perspectives on the everyday practices and macro-politics of race and gender in multi-ethnic societies. With attention to the specific political and cultural landscapes...... of the Nordic countries, Affectivity and Race draws on a variety of sources, including television programmes, news media, fictional literature, interviews, ethnographic observations, teaching curricula and policy documents, to explore the ways in which ideas about affectivity and emotion afford new insights...... into the experience of racial difference and the unfolding of political discourses on race in various social spheres. Organised around the themes of the politicisation of race through affect, the way that race produces affect and the affective experience of race, this interdisciplinary collection sheds light...

  4. Affectivity and Race

    DEFF Research Database (Denmark)

    This book presents new empirical studies of social difference in the Nordic welfare states, in order to advance novel theoretical perspectives on the everyday practices and macro-politics of race and gender in multi-ethnic societies. With attention to the specific political and cultural landscapes...... of the Nordic countries, Affectivity and Race draws on a variety of sources, including television programmes, news media, fictional literature, interviews, ethnographic observations, teaching curricula and policy documents, to explore the ways in which ideas about affectivity and emotion afford new insights...... into the experience of racial difference and the unfolding of political discourses on race in various social spheres. Organised around the themes of the politicisation of race through affect, the way that race produces affect and the affective experience of race, this interdisciplinary collection sheds light...

  5. αO-Conotoxin GeXIVA disulfide bond isomers exhibit differential sensitivity for various nicotinic acetylcholine receptors but retain potency and selectivity for the human α9α10 subtype.

    Science.gov (United States)

    Zhangsun, Dongting; Zhu, Xiaopeng; Kaas, Quentin; Wu, Yong; Craik, David J; McIntosh, J Michael; Luo, Sulan

    2017-12-01

    Nicotinic acetylcholine receptor (nAChR) subtypes exhibit distinct neuropharmacological properties that are involved in a range of neuropathological conditions, including pain, addiction, epilepsy, autism, schizophrenia, Tourette's syndrome, Alzheimer's and Parkinson's diseases, as well as many types of cancer. The α9α10 nAChR is a potential target in chronic pain, wound healing, the pathophysiology of the auditory system, and breast and lung cancers. αO-conotoxin GeXIVA is a potent antagonist of rat α9α10 nAChRs, with the 'bead' disulfide bond isomer displaying the lowest IC 50 of the three possible isomers. In the rat chronic constriction injury model of neuropathic pain, this isomer reduced mechanical hyperalgesia without affecting motor performance. Here, we report the effects of the three disulfide bond isomers of GeXIVA on human α9α10 nAChRs, other human nAChR subtypes, various rat nAChR subtypes, and 10 rat α9α10 nAChR mutants. The three isomers displayed only ∼5-fold difference in potency on the human vs rat α9α10 receptors and had similar affinities at wild-type rat α9α10 nAChRs and all 10 α9α10 receptor mutants. From these findings, the binding site and mechanism of action of GeXIVA on rat and human α9α10 nAChR was deduced to be different from that of other conotoxins targeting this nAChR subtype. GeXIVA is therefore a unique ligand that might prove useful for further probing of binding sites on the α9α10 nAChR. This article is part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools.' Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Affect and criminal responsibility

    Directory of Open Access Journals (Sweden)

    Drakić Dragiša S.

    2017-01-01

    Full Text Available In this article the author deals with an issue of relationship between the affect and criminal responsibility. In order to provide a multi-angle approach to analysis of this issue the author resorted to multidisciplinary - criminal law and psychiatric-psychological approach. Although the topic covered by this article is significant and complex, it appears to be of virtually no interest in the literature. For that reason the author's endeavor to research this topic should not go unmentioned. In the first part of the article the author tried to provide answers to some preliminary questions without which it would be impossible to understand the relationship between the affect and criminal responsibility. Those are the following questions: what are affects, what is their nature and intensity, how long they last and how they influence psychological functions of a person acting in affect? Central part of the article is dedicated to examining the importance of the affect as a phenomenon in criminal law dogma and in judicial rulings, as well as its effect on criminal responsibility. The author finds that acting in affect may be considered as a mitigating circumstance in the sentencing, but can also be a basis for mitigation of the sentence or even suspension of the sentence, as part of some general criminal law norms. Also, for certain offenses it may be considered as a favorable condition that renders that offence to be less grave. Finally, the affect may be considered as a psychological basis diminished, or even lack of, mental capacity. The last above mentioned issue receives special attention of the author, and claims that only the affect that is 'of extreme proportions' may lead to mental incapacity. Such affect is the one that 'demolishes restrains and removes reasonable and target-oriented actions'. In further analysis the author proposes criteria and methodology for assessment of person's sanity in criminal law and criminal procedure. Further

  7. Affectivity in the Liminal

    DEFF Research Database (Denmark)

    Thomassen, Bjørn

    In this paper I propose a return to the work of Arnold van Gennep, in order to briefly discuss how the terms of liminality and affectivity were always already connected. By linking the concept of liminality that van Gennep made famous to affectivity, we are actually not proposing new and alternat......In this paper I propose a return to the work of Arnold van Gennep, in order to briefly discuss how the terms of liminality and affectivity were always already connected. By linking the concept of liminality that van Gennep made famous to affectivity, we are actually not proposing new...... and alternative interpretations of what liminality is, or could be, taking it to territories distant from its place of origin, quite the contrary: we are moving the concept back to its rightful place in intellectual history and back to the core of its significance, back to the centre of human emotions trembling...... at the threshold. The paper contains three sections: a) liminality and affectivity in van Gennep’s life; b) liminality and affectivity as a theme in his work; c) liminality and affectivity as developed in the early reception of his work....

  8. Summary data of potency and parameter information from semi-mechanistic PKPD modeling of prolactin release following administration of the dopamine D2 receptor antagonists risperidone, paliperidone and remoxipride in rats

    Directory of Open Access Journals (Sweden)

    Amit Taneja

    2016-09-01

    Full Text Available We provide the reader with relevant data related to our recently published paper, comparing two mathematical models to describe prolactin turnover in rats following one or two doses of the dopamine D2 receptor antagonists risperidone, paliperidone and remoxipride, “A comparison of two semi-mechanistic models for prolactin release and prediction of receptor occupancy following administration of dopamine D2 receptor antagonists in rats” (Taneja et al., 2016 [1]. All information is tabulated. Summary level data on the in vitro potencies and the physicochemical properties is presented in Table 1. Model parameters required to explore the precursor pool model are presented in Table 2. In Table 3, estimated parameter comparisons for both models are presented, when separate potencies are estimated for risperidone and paliperidone, as compared to a common potency for both drugs. In Table 4, parameter estimates are compared when the drug effect is parameterized in terms of drug concentration or receptor occupancy.

  9. Factors affecting vaccine handling and storage practices among ...

    African Journals Online (AJOL)

    Background: Improper handling has been identified as one of the major reasons for the decline in vaccine potency at the time of administration. Loss of potency becomes evident when immunised individuals contract the diseases the vaccines were meant to prevent. Objective: Assessing the factors associated with vaccine ...

  10. Plant diversity and energy potency of community forest in East Kalimantan, Indonesia: Searching for fast growing wood species for energy production

    Directory of Open Access Journals (Sweden)

    RUDIANTO AMIRTA

    2016-05-01

    Full Text Available Abstract. Amirta R, Yuliansyah, Angi EM, Ananto BR, Setiyono B, Haqiqi MT, Septiana HA, Lodong M, Oktavianto RN. 2016. Plant diversity and energy potency of community forest in East Kalimantan, Indonesia: Searching for fast growing wood species for energy production. Nusantara Bioscience 8: 22-30. Nowadays, there is an increasing interest in intensifying the production and use of biomass to replace fossil fuels for the production of heat and electricity, especially for a remote area that generally abundance with the wood biomass resources including in East Kalimantan, Indonesia. In this work, diversity of plant species that commonly growth in community forest area of East Kutai District, East Kalimantan, Indonesia had been studied to point out their energy potency to be used as biomass feedstock for the electricity generated. Diversity of plant species in the community forest was evaluated by making 13 sampling plots with 20mx20m size approximately. Concurently, the energy properties of plant biomass such as proximate and ultimate compositions were also analyzed using ASTM methods. Results showed that more than 30 species of tropical trees and wood shrubs were grown in the community forest. The presence of them was classified into two different growth of origins: natural and artificial plantation, and also three different categories of plant resources: tree species from logged over forest, commercial fast growing plant tree species for the fiber production and woody shrubs. The highest dominancy and productivity was found in Paraserianthes falcataria (L. Nielsen since the wood biomass was artificially planted for the commercial purposes. Among the 31 plant species analyzed we found the highest energy potency was obtained from Cratoxylum cochinchinense (Lour. Blume that produced 3.17 MWh/ton, and the lowest was from Trema orientalis (L. Blume 0.97 MWh/ton. The woody shrubs species such as Vernonia amigdalina Delile., Piper aduncum L., Gliricidia

  11. A practical approach for the validation of sterility, endotoxin and potency testing of bone marrow mononucleated cells used in cardiac regeneration in compliance with good manufacturing practice

    Directory of Open Access Journals (Sweden)

    Gola Mauro

    2009-09-01

    Full Text Available Abstract Background Main scope of the EU and FDA regulations is to establish a classification criterion for advanced therapy medicinal products (ATMP. Regulations require that ATMPs must be prepared under good manufacturing practice (GMP. We have validated a commercial system for the determination of bacterial endotoxins in compliance with EU Pharmacopoeia 2.6.14, the sterility testing in compliance with EU Pharmacopoeia 2.6.1 and a potency assay in an ATMP constituted of mononucleated cells used in cardiac regeneration. Methods For the potency assay, cells were placed in the upper part of a modified Boyden chamber containing Endocult Basal Medium with supplements and transmigrated cells were scored. The invasion index was expressed as the ratio between the numbers of invading cells relative to cell migration through a control insert membrane. For endotoxins, we used a commercially available system based on the kinetic chromogenic LAL-test. Validation of sterility was performed by direct inoculation of TSB and FTM media with the cell product following Eu Ph 2.6.1 guideline. Results and discussion The calculated MVD and endotoxin limit were 780× and 39 EU/ml respectively. The 1:10 and 1:100 dilutions were selected for the validation. For sterility, all the FTM cultures were positive after 3 days. For TSB cultures, Mycetes and B. subtilis were positive after 5 and 3 days respectively. The detection limit was 1-10 colonies. A total of four invasion assay were performed: the calculated invasion index was 28.89 ± 16.82% (mean ± SD. Conclusion We have validated a strategy for endotoxin, sterility and potency testing in an ATMP used in cardiac regeneration. Unlike pharmaceutical products, many stem-cell-based products may originate in hospitals where personnel are unfamiliar with the applicable regulations. As new ATMPs are developed, the regulatory framework is likely to evolve. Meanwhile, existing regulations provide an appropriate structure for

  12. A practical approach for the validation of sterility, endotoxin and potency testing of bone marrow mononucleated cells used in cardiac regeneration in compliance with good manufacturing practice.

    Science.gov (United States)

    Soncin, Sabrina; Lo Cicero, Viviana; Astori, Giuseppe; Soldati, Gianni; Gola, Mauro; Sürder, Daniel; Moccetti, Tiziano

    2009-09-08

    Main scope of the EU and FDA regulations is to establish a classification criterion for advanced therapy medicinal products (ATMP). Regulations require that ATMPs must be prepared under good manufacturing practice (GMP). We have validated a commercial system for the determination of bacterial endotoxins in compliance with EU Pharmacopoeia 2.6.14, the sterility testing in compliance with EU Pharmacopoeia 2.6.1 and a potency assay in an ATMP constituted of mononucleated cells used in cardiac regeneration. For the potency assay, cells were placed in the upper part of a modified Boyden chamber containing Endocult Basal Medium with supplements and transmigrated cells were scored. The invasion index was expressed as the ratio between the numbers of invading cells relative to cell migration through a control insert membrane. For endotoxins, we used a commercially available system based on the kinetic chromogenic LAL-test. Validation of sterility was performed by direct inoculation of TSB and FTM media with the cell product following Eu Ph 2.6.1 guideline. The calculated MVD and endotoxin limit were 780x and 39 EU/ml respectively. The 1:10 and 1:100 dilutions were selected for the validation. For sterility, all the FTM cultures were positive after 3 days. For TSB cultures, Mycetes and B. subtilis were positive after 5 and 3 days respectively. The detection limit was 1-10 colonies. A total of four invasion assay were performed: the calculated invasion index was 28.89 +/- 16.82% (mean +/- SD). We have validated a strategy for endotoxin, sterility and potency testing in an ATMP used in cardiac regeneration. Unlike pharmaceutical products, many stem-cell-based products may originate in hospitals where personnel are unfamiliar with the applicable regulations. As new ATMPs are developed, the regulatory framework is likely to evolve. Meanwhile, existing regulations provide an appropriate structure for ensuring the safety and efficacy of the next generation of ATMPs. Personnel

  13. Caffeine has greater potency and efficacy than theophylline to reverse the motor impairment caused by chronic but not acute interruption of striatal dopaminergic transmission in rats.

    Science.gov (United States)

    Acuña-Lizama, Miguel M; Bata-García, José L; Alvarez-Cervera, Fernando J; Góngora-Alfaro, José L

    2013-07-01

    In order to assess whether caffeine and theophylline have the same potency and efficacy to reverse the impairment of motor function caused by acute or chronic interruption of striatal dopamine transmission, a comparison of their dose-response relationship was made in the acute model of haloperidol-induced catalepsy, and the chronic model of unilateral lesion of the dopamine nigrostriatal pathway with 6-hydroxydopamine. At equimolar doses, both drugs reduced catalepsy intensity and increased its onset latency in a dose-dependent fashion, showing comparable potencies and attaining the maximal effect at similar doses. Catalepsy intensity: caffeine ED₅₀ = 24.1 μmol/kg [95% CI, 18.4-31.5]; theophylline ED₅₀ = 22.0 μmol/kg [95% CI, 17.0-28.4]. Catalepsy latency: caffeine ED₅₀ = 27.0 μmol/kg [95% CI, 21.1-34.6]; theophylline ED₅₀ = 28.8 μmol/kg [95% CI, 22.5-36.7]. In one group of hemiparkinsonian rats (n = 5), caffeine caused a dose-dependent recovery of the contralateral forepaw stepping: ED₅₀ = 2.4 μmol/kg/day [95% CI, 1.9-3.1]), reaching its maximum at the dose of 5.15 μmol/kg/day. When the treatment of these same rats was switched to 5.15 μmol/kg/day of theophylline, the stepping recovery was only 51 ± 12% of that induced by caffeine. Assessing the dose-response relationship of theophylline in another group of hemiparkinsonian rats (n = 7) revealed that it caused stepping recovery in an all-or-none fashion. Thus, the three lower doses had no effect, but at the dose of 5.15 μmol/kg/day theophylline suddenly increased the stepping to 56 ± 5% of the maximal effect observed when the treatment of these same rats was switched to an equimolar dose of caffeine. Increasing the dose of theophylline up to 15.45 μmol/kg/day caused no further stepping improvement since it was only 41 ± 6% of the maximal effect produced by caffeine at the dose of 5.15 μmol/kg/day. Given that theophylline showed less potency and efficacy than caffeine to reverse the

  14. Dementia in affective disorder

    DEFF Research Database (Denmark)

    Kessing, L V; Olsen, E W; Mortensen, P B

    1999-01-01

    OBJECTIVE: The aim of the study was to investigate whether patients with affective disorder have increased risk of developing dementia compared to other groups of psychiatric patients and compared to the general population. METHOD: In the Danish psychiatric central register, 3363 patients...... with unipolar affective disorder, 518 patients with bipolar affective disorder, 1025 schizophrenic and 8946 neurotic patients were identified according to the diagnosis at the first ever discharge from psychiatric hospital during the period from 1970 to 1974. The rate of discharge diagnosis of dementia...... on readmission was estimated during 21 years of follow-up. In addition, the rates were compared with the rates for admission to psychiatric hospitals with a discharge diagnosis of dementia for the total Danish population. RESULTS: Patients with unipolar and with bipolar affective disorder had a greater risk...

  15. What affects women's participation?

    International Development Research Centre (IDRC) Digital Library (Canada)

    Karen Kershaw

    What affects women's participation? Variables. Men. Women. Presence. Caste, Age. Education. Political Experience. Attendance in Training. Region, Caste. Religion, Age. Number of Children. Political Experience. Attendance in training. Influence. Region, Education. Type of Family. Party Membership. Political Experience.

  16. Pain, Affect, and Attachment

    Directory of Open Access Journals (Sweden)

    Carl Eduard Scheidt

    2015-05-01

    Full Text Available Various psychodynamic processes may underlie the development of psychogenic pain disorder such as conversion, the displacement of affect, or narcissistic defenses. However, many of the processes suggested are related to a disorder of affect regulation. The term affect regulation in psychoanalytic literature refers to phenomena which are often described by the concept of alexithymia. Empirical observations suggest that alexithymia is correlated to insecure attachment, especially an insecure dismissing representation of attachment. Psychodynamic psychotherapy in psychogenic pain disorder should focus on the reintegration of split-off affects which may provoke intensive counter-transference and which in order to be used therapeutically must be linked to attachment experiences within and outside of the therapeutic relationship.

  17. Forward Affect Bridge.

    Science.gov (United States)

    Bonshtein, Udi; Torem, Moshe

    2017-01-01

    This article presents a modification of the affect bridge technique. The Forward Affect Bridge enables practitioners to create and maintain hope when it is missing. Hope is relevant for diminishing avoidance and being involved with necessary activities. The main idea is to build up a positive atmosphere in the here and now (relying on rapport), to amplify it, and to project it forward. By using clinical vignettes, the authors illustrate these techniques.

  18. Theoretical study of the HAP crystal growth inhibition potency of pyrophosphate, etidronate, citrate and phytate. Deciphered the adsorbed conformation of phytate on the HAP (001) surface

    Science.gov (United States)

    Fernández, David; Ortega-Castro, Joaquín; Frau, Juan

    2017-06-01

    The study of hydroxyapatite (HAP) crystal growth inhibitors has become an important field of research since HAP was identified as the main mineral component involved in pathological calcifications of soft tissues. In this work we performed a theoretical study of the deposition and the adsorption of a series of the most important HAP crystal inhibitors, such as pyrophosphate, etidronate, citrate and phytate, by means the Density Functional Theory. We showed that the adsorption energies of the inhibitors increased in the sequence: pyrophosphate functional groups of the molecules that interact with the HAP surface, and the total molecular negative charge. The study highlights phytate as the best inhibitor of pathological calcifications of the series, but also opened the door to further structural modifications of citrate that will match the inhibition potency of phytate.

  19. Replacement of in vivo human rabies vaccine potency testing by in vitro glycoprotein quantification using ELISA - Results of an international collaborative study.

    Science.gov (United States)

    Morgeaux, Sylvie; Poirier, Bertrand; Ragan, C Ian; Wilkinson, Dianna; Arabin, Ulrich; Guinet-Morlot, Françoise; Levis, Robin; Meyer, Heidi; Riou, Patrice; Shaid, Shahjahan; Volokhov, Dmitriy; Tordo, Noël; Chapsal, Jean-Michel

    2017-02-07

    Three different ELISAs quantifying rabies glycoprotein were evaluated as in vitro alternatives to the National Institutes of Health (NIH) in vivo potency test for batch release of human rabies vaccines. The evaluation was carried out as an international collaborative study supported by the European Partnership for Alternatives to Animal Testing (EPAA). This pre-validation study, the results of which are presented in this paper, compared three different ELISA designs, assessing their within- and between-laboratory precision. One of the ELISA designs was proposed to the European Directorate for the Quality of Medicines & HealthCare (EDQM) and accepted for an international collaborative study under the umbrella of the Biological Standardisation Programme. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. 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.

  1. Evaluation of Potency of Known Oximes (Pralidoxime, Trimedoxime, HI-6, Methoxime, Obidoxime to in vitro Reactivate Acetylcholinesterase Inhibited by Pesticides (Chlorpyrifos and Methylchlorpyrifos and Nerve Agent (Russian VX

    Directory of Open Access Journals (Sweden)

    Kamil Musílek

    2007-01-01

    Full Text Available Nerve agents and pesticides belong to the group of organophosphates. They are able to inhibit irreversibly the enzyme acetylcholinesterase (AChE. Acetylcholinesterase reactivators were designed for the treatment of nerve agent intoxications. Their potency to reactivate pesticide-inhibited AChE was many times evaluated. In this study, five commonly used AChE reactivators (pralidoxime, methoxime, HI-6, obidoxime, trimedoxime for the reactivation of AChE inhibited by two pesticides (chlorpyrifos and methylchlorpyrifos were used. Russian VX (nerve agent as a member of nerve agents’ family was taken for comparison. Obtained results show that oximes developed against nerve agent intoxication are less effective for intoxication with organophosphorus pesticides. Especially, methylchlorpyrifos-inhibited AChE was found to be poorly reactivated by the compounds used.

  2. Pharmacological Identification of a Guanidine-Containing β-Alanine Analogue with Low Micromolar Potency and Selectivity for the Betaine/GABA Transporter 1 (BGT1)

    DEFF Research Database (Denmark)

    Al-Khawaja, Anas Mohammad Ali; Petersen, Jette Gellert; Damgaard, Maria

    2014-01-01

    of the amino group in β-alanine or GABA, a series of compounds was generated, and their pharmacological activity assessed at human GAT subtypes. Using a cell-based [(3)H]GABA uptake assay, several selective inhibitors at human BGT1 were identified. The guanidine-containing compound 9 (2-amino-1......,4,5,6-tetrahydropyrimidine-5-carboxylic acid hydrochloride) displayed more than 250 times greater potency than the parent compound β-alanine at BGT1 and is thus the most potent inhibitor reported to date for this subtype (IC50 value of 2.5 µM). In addition, compound 9 displayed about 400, 16 and 40 times lower inhibitory...

  3. Determination of potency and paraspecific effects of Androctonus crassicauda (Olivier, 1807 antivenom against Mesobuthus gibbosus (Brullé, 1832 venom (Scorpiones: Buthidae

    Directory of Open Access Journals (Sweden)

    O. Ozkan

    2007-01-01

    Full Text Available Scorpion envenomation remains a real health problem in many countries. In scorpionism cases, it is often recommended that patients be treated with species-specific antivenom. Androctonus crassicauda venom has been used as antigen for antivenom production in Turkey, where this antivenom, called Turkish antivenom, has also been effective in the treatment of envenomation caused by species other than A. crassicauda. The present study aimed at determining the paraspecific effects and potency of the Turkish antivenom against Mesobuthus gibbosus (Brullé, 1832 venom. To assess the venom toxicity and the antivenom efficacy, we determined the Minimum Lethal Dose (MLD and the Minimum Effective Dose (MED instead of LD50 and ED50, respectively. Androctonus crassicauda antivenom was capable of neutralizing M. gibbosus venom (20 MLD. This was the first study indicating that A. crassicauda antivenom can be used for the treatment of Mesobuthus gibbosus stings, especially in Aegean Region, Turkey.

  4. Synthesis and anti-microbial potencies of 1-(2-hydroxyethyl)-3-alkylimidazolium chloride ionic liquids: microbial viabilities at different ionic liquids concentrations.

    Science.gov (United States)

    Hossain, M Ismail; El-Harbawi, Mohanad; Alitheen, Noorjahan Banu Mohamed; Noaman, Yousr Abdulhadi; Lévêque, Jean-Marc; Yin, Chun-Yang

    2013-01-01

    Three 1-(2-hydroxyethyl)-3-alkylimidazolium chloride room temperature ionic liquids (ILs) [2OHimC(n)][Cl]; (n=0, 1, 4) have been synthesized from the appropriate imidazole precursors and characterized by IR and NMR spectroscopies and elemental analysis. Their anti-microbial activities were investigated using the well-diffusion method. The viabilities of Escherichia coli, Aeromonas hydrophila, Listeria monocytogenes and Salmonella enterica as a function of IL concentrations were studied. The minimal inhibitory concentrations (MICs) and EC₅₀ values for the present ILs were within the concentration range from 60 to 125 mM and 23 to 73 mM. The anti-microbial potencies of the present ILs were compared to a standard antibiotic, gentamicin. The finding affords additional perspective on the level of ILs toxicity to aquatic lifeforms and yet, this characteristic can be readily harnessed to detect microbial growth and activity. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Increase of the ejaculatory potency by the systemic administration of aqueous crude extracts of cihuapatli (Montanoa genus) plants in spinal male rats.

    Science.gov (United States)

    Carro-Juárez, Miguel; Franco, Miguel Ángel; Rodríguez-Peña, María de Lourdes

    2014-01-01

    In the present study, evidence on the aphrodisiac activity of Montanoa frutescens and Montanoa grandiflora and a comparison with the aphrodisiac activity of Montanoa tomentosa is presented. By using the fictive ejaculation model in spinal male rats, electromyographic recordings of the genital motor pattern of ejaculation were obtained in the bulbospongiosus muscles and analyzed after the intravenous injection of aqueous crude extracts of Montanoa tomentosa, Montanoa frutescens, and Montanoa grandiflora. Results showed that the systemic administration of the aqueous crude extracts of Montanoa plants elicits a significant increase in the ejaculatory capacity of spinal male rats with very robust ejaculatory motor patterns that included the expression of tonic penile erections and penile movements and the potent expulsion of urethral contents. In conclusion, Montanoa frutescens and Montanoa grandiflora increase the ejaculatory potency with aphrodisiac activity similar to Montanoa tomentosa.

  6. Comparison of anorectic potencies of the trichothecenes T-2 toxin, HT-2 toxin and satratoxin G to the ipecac alkaloid emetine

    Directory of Open Access Journals (Sweden)

    Wenda Wu

    2015-01-01

    Full Text Available Trichothecene mycotoxins, potent translational inhibitors that are associated with human food poisonings and damp-building illnesses, are of considerable concern to animal and human health. Food refusal is a hallmark of exposure of experimental animals to deoxynivalenol (DON and other Type B trichothecenes but less is known about the anorectic effects of foodborne Type A trichothecenes (e.g., T-2 toxin, HT-2 toxin, airborne Type D trichothecenes (e.g., satratoxin G [SG] or functionally analogous metabolites that impair protein synthesis. Here, we utilized a well-described mouse model of food intake to compare the anorectic potencies of T-2 toxin, HT-2 toxin, and SG to that of emetine, a medicinal alkaloid derived from ipecac that inhibits translation. Intraperitoneal (IP administration with T-2 toxin, HT-2 toxin, emetine and SG evoked anorectic responses that occurred within 0.5 h that lasted up to 96, 96, 3 and 96 h, respectively, with lowest observed adverse effect levels (LOAELs being 0.1, 0.1, 2.5 and 0.25 mg/kg BW, respectively. When delivered via natural routes of exposure, T-2 toxin, HT-2 toxin, emetine (oral and SG (intranasal induced anorectic responses that lasted up to 48, 48, 3 and 6 h, respectively with LOAELs being 0.1, 0.1, 0.25, and 0.5 mg/kg BW, respectively. All four compounds were generally much more potent than DON which was previously observed to have LOAELs of 1 and 2.5 mg/kg BW after IP and oral dosing, respectively. Taken together, these anorectic potency data will be valuable in discerning the relative risks from trichothecenes and other translational inhibitors of natural origin.

  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. 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.

  9. Bis-picolinamide Ruthenium(III) Dihalide Complexes: Dichloride-to-Diiodide Exchange Generates Single trans Isomers with High Potency and Cancer Cell Selectivity.

    Science.gov (United States)

    Basri, Aida M; Lord, Rianne M; Allison, Simon J; Rodríguez-Bárzano, Andrea; Lucas, Stephanie J; Janeway, Felix D; Shepherd, Helena J; Pask, Christopher M; Phillips, Roger M; McGowan, Patrick C

    2017-05-05

    A library of new bis-picolinamide ruthenium(III) dihalide complexes of the type [RuX 2 L 2 ] (X=Cl or I, L=picolinamide) have been synthesised and characterised. The complexes exhibit different picolinamide ligand binding modes, whereby one ligand is bound (N,N) and the other bound (N,O). Structural studies revealed a mixture of cis and trans isomers for the [RuCl 2 L 2 ] complexes but upon a halide exchange reaction to yield [RuI 2 L 2 ], only single trans isomers were detected. High cytotoxic activity against human cancer cell lines was observed, with the potencies of some complexes similar to or better than cisplatin. The conversion to [RuI 2 L 2 ] substantially increased the activity towards cancer cell lines by more than twelvefold. The [RuI 2 L 2 ] complexes displayed potent activity against the A2780cis (cisplatin-resistant human ovarian cancer) cell line, with a more than fourfold higher potency than cisplatin. Equitoxic activity was observed against normoxic and hypoxic cancer cells, which indicates the potential to eradicate both the hypoxic and aerobic fractions of solid tumours with similar efficiency. The activity of selected complexes against non-cancer ARPE-19 cells was also tested. The [RuI 2 L 2 ] complexes were found to be more potent than the [RuCl 2 L 2 ] analogues and also more selective towards cancer cells with a selectivity factor in excess of sevenfold. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Ultra-low concentrations of naloxone selectively antagonize excitatory effects of morphine on sensory neurons, thereby increasing its antinociceptive potency and attenuating tolerance/dependence during chronic cotreatment.

    Science.gov (United States)

    Crain, S M; Shen, K F

    1995-11-07

    Ultra-low picomolar concentrations of the opioid antagonists naloxone (NLX) and naltrexone (NTX) have remarkably potent antagonist actions on excitatory opioid receptor functions in mouse dorsal root ganglion (DRG) neurons, whereas higher nanomolar concentrations antagonize excitatory and inhibitory opioid functions. Pretreatment of naive nociceptive types of DRG neurons with picomolar concentrations of either antagonist blocks excitatory prolongation of the Ca(2+)-dependent component of the action potential duration (APD) elicited by picomolar-nanomolar morphine and unmasks inhibitory APD shortening. The present study provides a cellular mechanism to account for previous reports that low doses of NLX and NTX paradoxically enhance, instead of attenuate, the analgesic effects of morphine and other opioid agonists. Furthermore, chronic cotreatment of DRG neurons with micromolar morphine plus picomolar NLX or NTX prevents the development of (i) tolerance to the inhibitory APD-shortening effects of high concentrations of morphine and (ii) supersensitivity to the excitatory APD-prolonging effects of nanomolar NLX as well as of ultra-low (femtomolar-picomolar) concentrations of morphine and other opioid agonists. These in vitro studies suggested that ultra-low doses of NLX or NTX that selectively block the excitatory effects of morphine may not only enhance the analgesic potency of morphine and other bimodally acting opioid agonists but also markedly attenuate their dependence liability. Subsequent correlative studies have now demonstrated that cotreatment of mice with morphine plus ultra-low-dose NTX does, in fact, enhance the antinociceptive potency of morphine in tail-flick assays and attenuate development of withdrawal symptoms in chronic, as well as acute, physical dependence assays.

  11. [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.

  12. 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.

  13. Affective responses to dance.

    Science.gov (United States)

    Christensen, Julia F; Pollick, Frank E; Lambrechts, Anna; Gomila, Antoni

    2016-07-01

    The objective of the present work was the characterization of mechanisms by which affective experiences are elicited in observers when watching dance movements. A total of 203 dance stimuli from a normed stimuli library were used in a series of independent experiments. The following measures were obtained: (i) subjective measures of 97 dance-naïve participants' affective responses (Likert scale ratings, interviews); and (ii) objective measures of the physical parameters of the stimuli (motion energy, luminance), and of the movements represented in the stimuli (roundedness, impressiveness). Results showed that (i) participants' ratings of felt and perceived affect differed, (ii) felt and perceived valence but not arousal ratings correlated with physical parameters of the stimuli (motion energy and luminance), (iii) roundedness in posture shape was related to the experience of more positive emotion than edgy shapes (1 of 3 assessed rounded shapes showed a clear effect on positiveness ratings while a second reached trend level significance), (iv) more impressive movements resulted in more positive affective responses, (v) dance triggered affective experiences through the imagery and autobiographical memories it elicited in some people, and (vi) the physical parameters of the video stimuli correlated only weakly and negatively with the aesthetics ratings of beauty, liking and interest. The novelty of the present approach was twofold; (i) the assessment of multiple affect-inducing mechanisms, and (ii) the use of one single normed stimulus set. The results from this approach lend support to both previous and present findings. Results are discussed with regards to current literature in the field of empirical aesthetics and affective neuroscience. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Factors that affect the onset of action of non-depolarizing neuromuscular blocking agents.

    Science.gov (United States)

    Kim, Yong Byum; Sung, Tae-Yun; Yang, Hong Seuk

    2017-10-01

    Neuromuscular blockade plays an important role in the safe management of patient airways, surgical field improvement, and respiratory care. Rapid-sequence induction of anesthesia is indispensable to emergency surgery and obstetric anesthesia, and its purpose is to obtain a stable airway, adequate depth of anesthesia, and appropriate respiration within a short period of time without causing irritation or damage to the patient. There has been a continued search for new neuromuscular blocking drugs (NMBDs) with a rapid onset of action. Factors that affect the onset time include the potency of the NMBDs, the rate of NMBDs reaching the effect site, the onset time by dose control, metabolism and elimination of NMBDs, buffered diffusion to the effect site, nicotinic acetylcholine receptor subunit affinity, drugs that affect acetylcholine (ACh) production and release at the neuromuscular junction, drugs that inhibit plasma cholinesterase, presynaptic receptors responsible for ACh release at the neuromuscular junction, anesthetics or drugs that affect muscle contractility, site and methods for monitoring neuromuscular function, individual variability, and coexisting disease. NMBDs with rapid onset without major adverse events are expected in the next few years, and the development of lower potency NMBDs will continue. Anesthesiologists should be aware of the use of NMBDs in the management of anesthesia. The choice of NMBD and determination of the appropriate dosage to modulate neuromuscular blockade characteristics such as onset time and duration of neuromuscular blockade should be considered along with factors that affect the effects of the NMBDs. In this review, we discuss the factors that affect the onset time of NMBDs.

  15. Amyloid Beta Peptides Differentially Affect Hippocampal Theta Rhythms In Vitro

    Directory of Open Access Journals (Sweden)

    Armando I. Gutiérrez-Lerma

    2013-01-01

    Full Text Available Soluble amyloid beta peptide (Aβ is responsible for the early cognitive dysfunction observed in Alzheimer's disease. Both cholinergically and glutamatergically induced hippocampal theta rhythms are related to learning and memory, spatial navigation, and spatial memory. However, these two types of theta rhythms are not identical; they are associated with different behaviors and can be differentially modulated by diverse experimental conditions. Therefore, in this study, we aimed to investigate whether or not application of soluble Aβ alters the two types of theta frequency oscillatory network activity generated in rat hippocampal slices by application of the cholinergic and glutamatergic agonists carbachol or DHPG, respectively. Due to previous evidence that oscillatory activity can be differentially affected by different Aβ peptides, we also compared Aβ25−35 and Aβ1−42 for their effects on theta rhythms in vitro at similar concentrations (0.5 to 1.0 μM. We found that Aβ25−35 reduces, with less potency than Aβ1−42, carbachol-induced population theta oscillatory activity. In contrast, DHPG-induced oscillatory activity was not affected by a high concentration of Aβ25−35 but was reduced by Aβ1−42. Our results support the idea that different amyloid peptides might alter specific cellular mechanisms related to the generation of specific neuronal network activities, instead of exerting a generalized inhibitory effect on neuronal network function.

  16. The Affective Turn

    Directory of Open Access Journals (Sweden)

    Alí Lara

    2013-11-01

    Full Text Available In the last decade studies on affect and emotions have become relevant in the social sciences. This is not just a fad guideline, but instead a simultaneous reader of public life changes and subjective experience, from which it is also being transformed the knowledge production. Such a trend has been known as ‘The Affective Turn’ within the Anglophone Academy. Here we will translate it as ‘El Giro Afectivo’. This turn, so far, has not dabbled in the social science literature that is written in Spanish. This paper draws on a singular panorama of discussions about contemporary social studies of affect and emotion, and it’s vertebrate by some of its expressions in the contemporary academy.

  17. Affected in the nightclub

    DEFF Research Database (Denmark)

    Demant, Jakob Johan

    2013-01-01

    The nightclub as a space is presented as a free and hedonistic place for pleasure. This space is also part of a wider socio-spatial-economic framework in which various forms of regulation apply to clubbers and the cultivation of affects. This paper researches marginal and contested forms of exper......The nightclub as a space is presented as a free and hedonistic place for pleasure. This space is also part of a wider socio-spatial-economic framework in which various forms of regulation apply to clubbers and the cultivation of affects. This paper researches marginal and contested forms...... of experiences within a club as a way of understanding the complexities of pleasure. The study does so by addressing experiences through the concept of affects, which is situated within a framework of a non-representational theory of space. Anxiety, pride, anger, shame and embarrassment are embodied...

  18. Mediatised affective activism

    DEFF Research Database (Denmark)

    Reestorff, Camilla Møhring

    2014-01-01

    , 2005) of protesting women and various human and non-human, mediatised (Hepp, 2013; Hjarvard, 2008; Lundby 2009) and localized actors. The article suggests that Femen’s protests undergo a dual process of mediatisation that aims to both generate a spreadable imaginary and enable communication between...... bodies by addressing affective registers. The mediatised ‘affective environment’ (Massumi, 2009) cues bodies and generates spreadability, yet it also produces disconnections. These disconnections might redistribute the ‘economy of recognizability’ (Butler and Athanasiou, 2013); however, the Femen...

  19. Radon affected areas: Scotland

    International Nuclear Information System (INIS)

    Miles, J.C.H.; Green, B.M.R.; Lomas, P.R.

    1993-01-01

    Board advice on radon in homes issued in 1990 specifies that areas of the UK where 1% or more of homes exceed the Action Level of 200 becquerels per cubic metre of air should be regarded as Affected Areas. Results of radon measurements in homes in the districts of Kincardine and Deeside and Gordon in Grampian Region and Caithness and Sutherland in Highland Region are mapped and used to delineate Affected Areas in these areas where required. The Scottish Office is advised to consider the desirability of developing guidance on precautions against radon in future homes. (author)

  20. Affectivity and race

    DEFF Research Database (Denmark)

    This book presents new empirical studies of social difference in the Nordic welfare states, in order to advance novel theoretical perspectives on the everyday practices and macro-politics of race and gender in multi-ethnic societies. With attention to the specific political and cultural landscapes...... of the Nordic countries, Affectivity and Race draws on a variety of sources, including television programmes, news media, fictional literature, interviews, ethnographic observations, teaching curricula and policy documents, to explore the ways in which ideas about affectivity and emotion afford new insights...

  1. Recurrence in affective disorder

    DEFF Research Database (Denmark)

    Kessing, L V; Olsen, E W; Andersen, P K

    1999-01-01

    The risk of recurrence in affective disorder is influenced by the number of prior episodes and by a person's tendency toward recurrence. Newly developed frailty models were used to estimate the effect of the number of episodes on the rate of recurrence, taking into account individual frailty toward...

  2. Affective public choice

    NARCIS (Netherlands)

    van Winden, F.A.A.M.; Casas Pardo, J.; Schwartz, P.

    2007-01-01

    This paper argues that due to the neglect of the affective side of human decision making we find it hard to explain political economic phenomena such as tax revolts, voting, political rituals, terrorism, and entitlements. Taking into account the action tendencies of emotions like resentment, hatred,

  3. Affective Tourism Ethnography

    NARCIS (Netherlands)

    Buda, Dorina; Tucker, Hazel

    2015-01-01

    In this paper we aim to advance the concept of affective tourism ethnography. We take ethnography to refer to a research strategy rather than simply a methodological tool. This is because ethnography entails methods (individual interviews, focus groups, participant observation amongst others) and

  4. Factors affecting nuclear development

    International Nuclear Information System (INIS)

    Stevens, G.H.; Girouard, P.

    1995-01-01

    Among the factors affecting nuclear development, some depend more or less on public authorities, but many are out of public authorities control (foreign policies, market and deregulation, socials and environmental impacts, public opinion). As far as possible, the following study tries to identify those factors. (D.L.). 2 photos

  5. What Variables Affect Solubility?

    Science.gov (United States)

    Baker, William P.; Leyva, Kathryn

    2003-01-01

    Helps middle school students understand the concept of solubility through hands-on experience with a variety of liquids and solids. As they explore factors that affect solubility and saturation, students gain content mastery and an understanding of the inquiry process. Also enables teachers to authentically assess student performance on several…

  6. Seasonal Affective Disorder (SAD)

    Science.gov (United States)

    ... SAD. This decrease in sunlight may disrupt your body's internal clock and lead to feelings of depression. Serotonin levels. A drop in serotonin, a brain chemical (neurotransmitter) that affects mood, ... disrupt the balance of the body's level of melatonin, which plays a role in ...

  7. Personalized affective music player

    NARCIS (Netherlands)

    Janssen, Joris H.; van den Broek, Egon; Westerink, Joyce H.D.M.; Cohn, J.; Nijholt, Antinus; Pantic, Maja

    2009-01-01

    We introduce and test an affective music player (AMP) that selects music for mood enhancement. Through a concise overview of content, construct, and ecological validity, we elaborate five considerations that form the foundation of the AMP. Based on these considerations, computational models are

  8. CRISPR/Cas9-mediated gene knockout is insensitive to target copy number but is dependent on guide RNA potency and Cas9/sgRNA threshold expression level.

    Science.gov (United States)

    Yuen, Garmen; Khan, Fehad J; Gao, Shaojian; Stommel, Jayne M; Batchelor, Eric; Wu, Xiaolin; Luo, Ji

    2017-11-16

    CRISPR/Cas9 is a powerful gene editing tool for gene knockout studies and functional genomic screens. Successful implementation of CRISPR often requires Cas9 to elicit efficient target knockout in a population of cells. In this study, we investigated the role of several key factors, including variation in target copy number, inherent potency of sgRNA guides, and expression level of Cas9 and sgRNA, in determining CRISPR knockout efficiency. Using isogenic, clonal cell lines with variable copy numbers of an EGFP transgene, we discovered that CRISPR knockout is relatively insensitive to target copy number, but is highly dependent on the potency of the sgRNA guide sequence. Kinetic analysis revealed that most target mutation occurs between 5 and 10 days following Cas9/sgRNA transduction, while sgRNAs with different potencies differ by their knockout time course and by their terminal-phase knockout efficiency. We showed that prolonged, low level expression of Cas9 and sgRNA often fails to elicit target mutation, particularly if the potency of the sgRNA is also low. Our findings provide new insights into the behavior of CRISPR/Cas9 in mammalian cells that could be used for future improvement of this platform. Published by Oxford University Press on behalf of Nucleic Acids Research 2017.

  9. Evaluation and validation of a single-dilution potency assay based upon serology of vaccines containing diphtheria toxoid: analysis for consistency in production and testing at the laboratory of the Control of Biological Products of the RIVM

    NARCIS (Netherlands)

    Akkermans AM; Hendriksen CFM; Marsman FR; de Jong WH; van de Donk HJM

    1993-01-01

    A single-dilution assay can be a valid procedure to demonstrate that a product exceeds the minimal requirement given for potency provided that consistency in production and testing has been proven. Information is presented justifying the use of a single dilution assay based upon quantitative

  10. Yes, you can? A speaker's potency to act upon his words orchestrates early neural responses to message-level meaning.

    Science.gov (United States)

    Bornkessel-Schlesewsky, Ina; Krauspenhaar, Sylvia; Schlesewsky, Matthias

    2013-01-01

    Evidence is accruing that, in comprehending language, the human brain rapidly integrates a wealth of information sources-including the reader or hearer's knowledge about the world and even his/her current mood. However, little is known to date about how language processing in the brain is affected by the hearer's knowledge about the speaker. Here, we investigated the impact of social attributions to the speaker by measuring event-related brain potentials while participants watched videos of three speakers uttering true or false statements pertaining to politics or general knowledge: a top political decision maker (the German Federal Minister of Finance at the time of the experiment), a well-known media personality and an unidentifiable control speaker. False versus true statements engendered an N400 - late positivity response, with the N400 (150-450 ms) constituting the earliest observable response to message-level meaning. Crucially, however, the N400 was modulated by the combination of speaker and message: for false versus true political statements, an N400 effect was only observable for the politician, but not for either of the other two speakers; for false versus true general knowledge statements, an N400 was engendered by all three speakers. We interpret this result as demonstrating that the neurophysiological response to message-level meaning is immediately influenced by the social status of the speaker and whether he/she has the power to bring about the state of affairs described.

  11. Insight into the interactions, residue snorkeling, and membrane disordering potency of a single antimicrobial peptide into different lipid bilayers.

    Directory of Open Access Journals (Sweden)

    Majid Jafari

    Full Text Available Pardaxin, with a bend-helix-bend-helix structure, is a membrane-active antimicrobial peptide that its membrane activity depends on the lipid bilayer composition. Herein, all-atom molecular dynamics (MD simulations were performed to provide further molecular insight into the interactions, structural dynamics, orientation behavior, and cationic residues snorkeling of pardaxin in the DMPC, DPPC, POPC, POPG, POPG/POPE (3:1, and POPG/POPE (1:3 lipid bilayers. The results showed that the C-terminal helix of the peptide was maintained in all six types of the model-bilayers and pardaxin was tilted into the DMPC, DPPC, and POPG/POPE mixed bilayers more than the POPC and POPG bilayers. As well as, the structure of zwitterionic membranes was more affected by the peptide than the anionic bilayers. Taken together, the study demonstrated that the cationic residues of pardaxin snorkeled toward the interface of lipid bilayers and all phenylalanine residues of the peptide played important roles in the peptide-membrane interactions. We hope that this work will provide a better understanding of the interactions of antimicrobial peptides with the membranes.

  12. Affect in electoral politics.

    Science.gov (United States)

    Glaser, J; Salovey, P

    1998-01-01

    Recent U.S. history provides vivid illustrations of the importance of politicians' emotional displays in subsequent judgments of them. Yet, a review of empirical research on the role of affect (emotion, mood, and evaluation) in electoral politics reveals little work that has focused on the impact of candidates' emotional expression on voters' preferences for them. A theoretical framework is proposed to identify psychological mechanisms by which a target's displays of emotion influence judgments of that target. Findings from the emerging literature on emotions and politics challenge the traditional assumption of political science that voters make decisions based solely on the cold consideration of nonaffectively charged information. The affect and politics literature, although somewhat unfocused and broad, represents an interdisciplinary domain of study that contributes to the understanding of both electoral politics and social interaction more generally.

  13. Affective public choice

    OpenAIRE

    van Winden, F.A.A.M.; Casas Pardo, J.; Schwartz, P.

    2007-01-01

    This paper argues that due to the neglect of the affective side of human decision making we find it hard to explain political economic phenomena such as tax revolts, voting, political rituals, terrorism, and entitlements. Taking into account the action tendencies of emotions like resentment, hatred, shame, fear, and hope, makes these kinds of behavior better understandable and predictable. To phrase the argument of this paper in a more polemical way: Who cannot stand the heat should stay out ...

  14. Factors Affecting Wound Healing

    OpenAIRE

    Guo, S.; DiPietro, L.A.

    2010-01-01

    Wound healing, as a normal biological process in the human body, is achieved through four precisely and highly programmed phases: hemostasis, inflammation, proliferation, and remodeling. For a wound to heal successfully, all four phases must occur in the proper sequence and time frame. Many factors can interfere with one or more phases of this process, thus causing improper or impaired wound healing. This article reviews the recent literature on the most significant factors that affect cutane...

  15. 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

  16. 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

    There is currently no standard paradigm for hazard and human risk assessment of environmental metabolites for agrochemicals. Using an actual case study, solutions to challenges faced are described and used to propose a generic concept to address risk posed by metabolites to human safety. A novel approach - built on the foundation of predicted human exposures to metabolites in various compartments (such as food and water), the threshold of toxicological concern (TTC) and the concept of comparative toxicity - was developed for environmental metabolites of a new chemical, sulfoxaflor (X11422208). The ultimate aim was to address the human safety of the metabolites with the minimum number of in vivo studies, while at the same time, ensuring that human safety would be considered addressed on a global regulatory scale. The third component, comparative toxicity, was primarily designed to determine whether the metabolites had the same or similar toxicity profiles to their parent molecule, and also to one another. The ultimate goal was to establish whether the metabolites had the potential to cause key effects - such as cancer and developmental toxicity, based on mode-of-action (MoA) studies - and to develop a relative potency factor (RPF) compared to the parent molecule. Collectively, the work presented here describes the toxicology programme developed for sulfoxaflor and its metabolites, and how it might be used to address similar future challenges aimed at determining the relevance of the metabolites from a human hazard and risk perspective. Sulfoxaflor produced eight environmental metabolites at varying concentrations in various compartments - soil, water, crops and livestock. The MoA for the primary effects of the parent molecule were elucidated in detail and a series of in silico, in vitro, and/or in vivo experiments were conducted on the environmental metabolites to assess relative potency of their toxicity profiles when compared to the parent. The primary metabolite

  17. 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

  18. Social and Affective Robotics Tutorial

    NARCIS (Netherlands)

    Pantic, Maja; Evers, Vanessa; Deisenroth, Marc; Merino, Luis; Schuller, Björn

    2016-01-01

    Social and Affective Robotics is a growing multidisciplinary field encompassing computer science, engineering, psychology, education, and many other disciplines. It explores how social and affective factors influence interactions between humans and robots, and how affect and social signals can be

  19. Ultrasonic variables affecting inspection

    International Nuclear Information System (INIS)

    Lautzenheiser, C.E.; Whiting, A.R.; McElroy, J.T.

    1977-01-01

    There are many variables which affect the detection of the effects and reproducibility of results when utilizing ultrasonic techniques. The most important variable is the procedure, as this document specifies, to a great extent, the controls that are exercised over the other variables. The most important variable is personnel with regards to training, qualification, integrity, data recording, and data analysis. Although the data is very limited, these data indicate that, if the procedure is carefully controlled, reliability of defect detection and reproducibility of results are both approximately 90 percent for reliability of detection, this applies to relatively small defects as reliability increases substantially as defect size increases above the recording limit. (author)

  20. Risk, Affect and Emotion

    Directory of Open Access Journals (Sweden)

    Jens O. Zinn

    2006-01-01

    Full Text Available For a long time theorising has underestimated the importance of affect and emotion in decision making and the management of risk and uncertainty. In relatively one-sided interpretations emotions were often interpreted as threats for rational decision making, and could be triggered by uncertainties, which would go along with social change. Recent interdisciplinary research has shown the importance to acknowledge the more complex link between reasoning and emotions. The article outlines different perspectives on emotion in risk research of economics, psychology and sociology and argues for further research. URN: urn:nbn:de:0114-fqs0601293

  1. The Affective Turn

    DEFF Research Database (Denmark)

    Carnera, Alexander

    2012-01-01

    ’ (Governmentality) related to different forms of control, and on the other hand new modes of existences connected to co-operation, social innovation and experimental projects. The paper then argues for a more positive conception of biopolitics using self-management as a strategy since it is through self...... organizing good affective encounters based on limitations enhance and facilitate the performative dimension of self-management. Finally, the paper addresses the problem of critique confronting self-relation with Spinoza's ethics as an ethical difference of powe...

  2. The Potency of White Rice (Oryza sativa), Black Rice (Oryza sativa L. indica), and Red Rice (Oryza nivara) as Antioxidant and Tyrosinase Inhibitor

    Science.gov (United States)

    Batubara, I.; Maharni, M.; Sadiah, S.

    2017-04-01

    Rice is known to have many beneficial biological activities and is often used as “bedak dingin”, a face powder. The content of vitamins, minerals, fiber, and several types of antioxidants, such as ferulic acid, phytic acid, tocopherol, and oryzanols [1-2] are predicted to be potential as a tyrosinase inhibitor. The purpose of this study is to determine the potency of extracts from there types of rice, namely white, red, and black rice as an antioxidant and tyrosinase inhibitor. The rice was extracted with three different solvents, n-hexane, ethyl acetate, and methanol. The results showed that the highest antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl method was found in the methanol extract of black rice (IC50 290 μg/mL). Meanwhile, ethyl acetate extract of white rice has the highest antioxidant activity withphosphomolybdic acid method (41 mmol α-tocopherol equivalents/g sample). Thus, methanol extract of black rice and ethyl acetate extract of white rice are potential as an antioxidant. For tyrosinase inhibitor, n-hexane extract of red rice (IC50 3156 μg/mL) was the most active extract. The active component for radical scavenging is polar compound and for antioxidant by phosphomolybdate method is less polar compounds in black rice methanol extract based on TLC bioautogram. In conclusion, the black rice is the most potent in antioxidant while red rice is for tyrosinase inhibition.

  3. Adding an Artificial Tail—Anchor to a Peptide-Based HIV-1 Fusion Inhibitor for Improvement of Its Potency and Resistance Profile

    Directory of Open Access Journals (Sweden)

    Shan Su

    2017-11-01

    Full Text Available Peptides derived from the C-terminal heptad repeat (CHR of human immunodeficiency virus type 1 (HIV-1 envelope protein transmembrane subunit gp41, such as T20 (enfuvirtide, can bind to the N-terminal heptad repeat (NHR of gp41 and block six-helix bundle (6-HB formation, thus inhibiting HIV-1 fusion with the target cell. However, clinical application of T20 is limited because of its low potency and genetic barrier to resistance. HP23, the shortest CHR peptide, exhibits better anti-HIV-1 activity than T20, but the HIV-1 strains with E49K mutations in gp41 will become resistant to it. Here, we modified HP23 by extending its C-terminal sequence using six amino acid residues (E6 and adding IDL (Ile-Asp-Leu to the C-terminus of E6, which is expected to bind to the shallow pocket in the gp41 NHR N-terminal region. The newly designed peptide, designated HP23-E6-IDL, was about 2- to 16-fold more potent than HP23 against a broad spectrum of HIV-1 strains and more than 12-fold more effective against HIV-1 mutants resistant to HP23. These findings suggest that addition of an anchor–tail to the C-terminus of a CHR peptide will allow binding with the pocket in the gp41 NHR that may increase the peptide’s antiviral efficacy and its genetic barrier to resistance.

  4. The effect of honey bee venom on the differentiation potency of D-alpha tocopheryl succinate (vitamin E on HL-60 promyelocytic leukemia cell line.

    Directory of Open Access Journals (Sweden)

    mohammad Nabiuni

    2014-01-01

    Full Text Available Background: Acute promyelocytic leukemia is the most malignant type of myeloid leukemia characterized by chromosomal translocation (15 and 17 and also blocking the cells in promyelocytic stage of differentiation into myeloid. Nowadays, differentiation therapy is used to treat leukemia. Previous studies indicate that vitamin E inhibits proliferation and also induces differentiation of HL-60 cell line towards monocyte. Since high concentrations of vitamin E to induce differentiation have many side effects, the search for alternative compounds is inevitable. Regarding anti- proliferative and anti-cancer effect of bee venom (BV, in this study the effect of BV on alpha tocopheryl succinate function in differentiation was examined. Materials and Methods: In this study cellular differentiation was tested by immunocytochemistry ,Wright-Giemsa staining and NBT reduction.Data were analyzed using one-way ANOVA test and Instate 3 software. Results: The results showed that BV in non-toxic concentrations can increase the differentiation potency of vitamin E on HL-60 cancer cell line. Conclusion: Non- toxic concentration of BV can increase differentiational effects of vitamin E and it is expected that BV can increases the differentiating potential of differentiator components in the future .

  5. Relative potency of albendazole and its sulfoxide metabolite in two in vitro tests for developmental toxicity: the rat whole embryo culture and the mouse embryonic stem cell test.

    Science.gov (United States)

    Eckardt, Kathrin; Kaltenhäuser, Johanna; Kilb, Caroline; Seiler, Andrea; Stahlmann, Ralf

    2012-11-01

    The benzimidazole carbamate albendazole (ABZ), a potent anthelmintic, is a teratogenic compound in rats. At present it is unclear to which degree this effect is caused by the parent compound or its major metabolite, albendazole sulfoxide (ASO). Both substances were studied separately and in combinations to mimic incomplete bioactivation in two in vitro tests: mouse embryonic stem cell test (EST) and rat whole embryo culture (WEC). In both assays, ABZ and mixtures with ASO induced detrimental effects at lower concentrations compared to ASO alone. While ABZ caused half-maximal effects on cardiomyocyte differentiation at a mean concentration of 0.26 μM (EST) and dysmorphogenic development of rat embryos at 3.7 μM (WEC), effective concentrations of ASO were similar in both assays (10-13 μM). By using WEC and EST we demonstrate that ABZ exhibits stronger inherent embryotoxic potency although ASO might be the proximate teratogen in vivo because of higher plasma concentrations. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Mixed halogenated dioxins/furans (PXDD/Fs) and biphenyls (PXBs) in food: occurrence and toxic equivalent exposure using specific relative potencies.

    Science.gov (United States)

    Fernandes, Alwyn R; Mortimer, David; Wall, Richard J; Bell, David R; Rose, Martin; Carr, Melanie; Panton, Sean; Smith, Frankie

    2014-12-01

    The occurrence of nineteen mixed halogenated (bromo-chloro) dibenzo-p-dioxins, dibenzofurans (PXDD/Fs) and biphenyls (PXBs) in a range of foods (n>100) was investigated. The analytical methodology used dual activated carbon column fractionation with high resolution mass spectrometric measurement (13,500-15,000 res). Occurrence was observed in most commonly consumed foods but the most frequent detections of these environmental contaminants were made in shellfish and offal. The concentrations of the individual compounds were condensed into toxic equivalents (TEQs) using recently reported relative potency values. Although representing only a small subset of the full range of toxic PXDD/Fs and PXBs, the TEQs estimated for these compounds ranged from 0.2% to approximately 15% (depending on the food matrix) of the corresponding TEQ for the fully chlorinated analogues. This finding is of great toxicological importance as it implies that a potentially greater magnitude of TEQ could be associated with the full range of toxic PXDD/Fs and PXBs, thus making a significant contribution to dioxin-like toxicity from the diet, to human exposure. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  7. Reversion of somatic mutations of the respiratory syncytial virus-specific human monoclonal antibody Fab19 reveal a direct relationship between association rate and neutralizing potency.

    Science.gov (United States)

    Bates, John T; Keefer, Christopher J; Utley, Thomas J; Correia, Bruno E; Schief, William R; Crowe, James E

    2013-04-01

    The role of affinity in determining neutralizing potency of mAbs directed against viruses is not well understood. We investigated the kinetic, structural, and functional advantage conferred by individual naturally occurring somatic mutations in the Ab H chain V region of Fab19, a well-described neutralizing human mAb directed to respiratory syncytial virus. Comparison of the affinity-matured Ab Fab19 with recombinant Fab19 Abs that were variants containing reverted amino acids from the inferred unmutated ancestor sequence revealed the molecular basis for affinity maturation of this Ab. Enhanced binding was achieved through mutations in the third H chain CDR (HCDR3) that conferred a markedly faster on-rate and a desirable increase in antiviral neutralizing activity. In contrast, most somatic mutations in the HCDR1 and HCDR2 regions did not significantly enhance Ag binding or antiviral activity. We observed a direct relationship between the measured association rate (Kon) for F protein and antiviral activity. Modeling studies of the structure of the Ag-Ab complex suggested the HCDR3 loop interacts with the antigenic site A surface loop of the respiratory syncytial virus F protein, previously shown to contain the epitope for this Ab by experimentation. These studies define a direct relationship of affinity and neutralizing activity for a viral glycoprotein-specific human mAb.

  8. Evaluation of the resolving potency of a novel reconstruction filter on periodontal ligament space with dental cone-beam CT: a quantitative phantom study

    Science.gov (United States)

    Houno, Yuuki; Hishikawa, Toshimitsu; Gotoh, Ken-ichi; Naitoh, Munetaka; Ariji, Eiichiro; Kodera, Yoshie

    2014-03-01

    Diagnosis of the alveolar bone condition is important for the treatment planning of periodontal disease. Especially the determination of periodontal ligament space is the most important remark because it represents the periodontal tissue support for tooth retention. However, owing to the image blur of the current cone-beam CT (CBCT) imaging technique, the periodontal ligament space is difficult to visualize. In this study, we developed an original periodontal ligament phantom (PLP) and evaluated the image quality of simulated periodontal ligament space using a novel reconstruction filter for CBCT that emphasized high frequency component. PLP was composed from two resin blocks of different materials, the bone equivalent block and the dentine equivalent block. They were assembled to make continuously changing space from 0.0 to 1.0 millimeter that mimics periodontal ligament space. PLP was placed in water and the image was obtained by using Alphard-3030 dental cone-beam CT (Asahi Roentgen Industry Co., Ltd.). Then we reconstructed the projection data with a novel reconstruction filter. The axial images were compared with conventional reconstructed images. In novel filter reconstruction images, 0.4 millimeter of the space width was steadily detected by calculation of pixel value, on the other hand 0.6 millimeter was in conventional images. With our method, the resolving potency of conebeam CT images was improved.

  9. [Assessment of the sensitizing potency of cosmetic ingredients and commodities. How will the ingredients of cosmetics and commodities be tested in Europe today and tomorrow?].

    Science.gov (United States)

    Peiser, M; Platzek, T; Luch, A

    2012-03-01

    Cosmetics and certain commodities are applied or used by consumers directly on the skin. Creams may remain on the skin for longer periods, hair is dyed multiple times per year, nickel ions can be released from studs and piercings in areas of skin damage or migrate from toy materials into the skin of children. Accordingly, using or handling such products always entails a risk for developing a contact allergy. Moreover, daily usage and repeated contacts to certain cosmetics and commodities might lead to repeated elicitation of contact eczema in people already sensitized against allergenic ingredients. Unfortunately, contact allergy is not curable. For the assessment of the allergenic potential of chemicals, only testing based on animal experiments was available in the past. In 2003, the 7(th) amendment of the Cosmetics Directive 76/768/EWG laid down a ban on animal testing of cosmetic ingredients and from 2013 a general marketing ban of such products as well. Therefore, the development and validation of non-animal methods for assessing the toxicological endpoint sensitization/allergenic potency of chemicals is a major task for the years ahead and remains equally a challenge for industry and regulatory agencies.

  10. Quantitative structure-activity relationship and molecular docking revealed a potency of anti-hepatitis C virus drugs against human corona viruses.

    Science.gov (United States)

    Elfiky, Abdo A; Mahdy, Samah M; Elshemey, Wael M

    2017-06-01

    A number of human coronaviruses (HCoVs) were reported in the last and present centuries. Some outbreaks of which (eg, SARS and MERS CoVs) caused the mortality of hundreds of people worldwide. The problem of finding a potent drug against HCoV strains lies in the inability of finding a drug that stops the viral replication through inhibiting its important proteins. In spite of its limited efficacy and potential side effects, Ribavirin is extensively used as a first choice against HCoVs. Therefore, scientists reverted towards the investigation of different drugs that can more specifically target proteins. In this study, four anti-HCV drugs (one approved by FDA and others under clinical trials) are tested against HCoV polymerases. Quantitative Structure-Activity Relationship (QSAR) and molecular docking are both used to compare the performance of the selected nucleotide inhibitors to their parent nucleotides and Ribavirin. Both QSAR and molecular docking showed that IDX-184 is superior compared to Ribavirin against MERS CoV, a result that was also reported for HCV. MK-0608 showed a performance that is comparable to Ribavirin. We strongly suggest an in vitro study on the potency of these two drugs against MERS CoV. © 2017 Wiley Periodicals, Inc.

  11. 4-Aminopyridyl-based CYP51 inhibitors as anti-Trypanosoma cruzi drug leads with improved pharmacokinetic profile and in vivo potency.

    Science.gov (United States)

    Calvet, Claudia M; Vieira, Debora F; Choi, Jun Yong; Kellar, Danielle; Cameron, Michael D; Siqueira-Neto, Jair Lage; Gut, Jiri; Johnston, Jonathan B; Lin, Li; Khan, Susan; McKerrow, James H; Roush, William R; Podust, Larissa M

    2014-08-28

    CYP51 is a P450 enzyme involved in the biosynthesis of the sterol components of eukaryotic cell membranes. CYP51 inhibitors have been developed to treat infections caused by fungi, and more recently the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease. To specifically optimize drug candidates for T. cruzi CYP51 (TcCYP51), we explored the structure-activity relationship (SAR) of a N-indolyl-oxopyridinyl-4-aminopropanyl-based scaffold originally identified in a target-based screen. This scaffold evolved via medicinal chemistry to yield orally bioavailable leads with potent anti-T. cruzi activity in vivo. Using an animal model of infection with a transgenic T. cruzi Y luc strain expressing firefly luciferase, we prioritized the biaryl and N-arylpiperazine analogues by oral bioavailability and potency. The drug-target complexes for both scaffold variants were characterized by X-ray structure analysis. Optimization of both binding mode and pharmacokinetic properties of these compounds led to potent inhibitors against experimental T. cruzi infection.

  12. Engineering of a novel zipFv using leucine zipper motif against rabies virus glycoprotein G with improved protection potency in vivo.

    Science.gov (United States)

    Xi, Hualong; Zhang, Kaixin; Yin, Yanchun; Gu, Tiejun; Sun, Qing; Li, Zhuang; Cheng, Yue; Jiang, Chunlai; Kong, Wei; Wu, Yongge

    2017-06-01

    Rabies is an acute zoonotic infectious disease with a high fatality rate but is preventable with vaccination and rabies immunoglobulin (RIG). The single-chain Fv fragment (scFv), a small engineered antigen-binding protein derived from antibody variable heavy (V H ) and light (V L ) chains connected by a peptide linker, can potentially be used to replace RIG. Here, we produced two peptides V H -JUN-HIS and V L -FOS-HA separately in Escherichia coli and assembled them to form zipFv successfully in vitro. The new zipFv utilizes FOS and JUN leucine zippers to form an antibody structure similar to the IgG counterpart with two free N-terminal ends of V H and V L . The zipFv protein showed notable improvement in binding ability and affinity over its corresponding scFv. The zipFv also demonstrated greater stability in serum and the same protective rate as RIG against challenge with a standard rabies virus (CVS-24) in mice. Our results indicated zipFv as a novel and efficient antibody form with enhanced neutralizing potency. Copyright © 2017. Published by Elsevier B.V.

  13. Cytotoxic potency of self-assembled Ruthenium(II-NHC complexes with pincer type 2, 6-bis(N-methylimidazolylidene/benzimidazolylidenepyrazine ligands

    Directory of Open Access Journals (Sweden)

    Gourisannkar Roymahapatra

    2015-01-01

    Full Text Available Objective: To study the cytotoxic potency of self-assembled Ruthenium(II-NHC complexes with 2,6-di-(N-methylimidazolylidene/benzimidazolylidenepyrazine ligands. Materials and Methods: Ru(II-N-heterocyclic (Ru-NHC complexes, Bis-[2,6-di-(N-methylimidazol-2-ylidenepyrazine]ruthenium(II hexaflurophosphate (3, Bis-[2,6-di-(N-methylbenzimidazol-2-ylidenepyrazine]ruthenium(II hexaflurophosphate (4 have been synthesized from corresponding ligands 2,6-di-(N-methylimidazoliumpyrazine dichloride (1; 2,6-di-(N-methylbenzimidazoliumpyrazine dichloride (2. Complexes were studied to determine their pro-apoptotic activity against HCT15 and Hep2 cell lines, and antimicrobial activity against Pseudomonas aeruginosa, Staphylococcus epidermidis and Candida albicans. Results: Both, complex 3 and 4, formed a nanosphere structure in aqueous growth medium. Cytotoxicity study revealed that complex 3 was more effective than complex 4. Complexes mainly target cellular DNA and bacterial cell wall. Conclusion: This is the first report on the formation of nanoball structure of Ru(II-NHC complexes. Thus, complex 3 provides a new insight to develop antitumor or antimicrobial drug.

  14. Potenciální mikrobiologické nebezpečí v současných trendech kosmetiky - bio, vegan, raw.

    OpenAIRE

    Jančíková, Simona

    2017-01-01

    Bio-, vegan- a raw-kosmetika patří k stále oblíbenějším druhům kosmetických produktů z důvodu absence syntetických látek a konzervantů, z tohoto hlediska se ale zvyšuje pravděpodobnost mikrobiální kontaminace. Předmětem práce je tedy především praktické zjištění potenciální mikrobiologické kontaminace pomocí zátěžového testu a také stanovení aktivních složek v kosmetických přípravcích. V teorii byla zpracována legislativa kosmetických přípravků, a také informace o certifikátech, které se pro ...

  15. Anorectic activities of serotonin uptake inhibitors: correlation with their potencies at inhibiting serotonin uptake in vivo and /sup 3/H-mazindol binding in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Angel, I.; Taranger, M.A.; Claustre, Y.; Scatton, B.; Langer, S.Z.

    1988-01-01

    The mechanism of anorectic action of several serotonin uptake inhibitors was investigated by comparing their anorectic potencies with several biochemical and pharmacological properties and in reference to the novel compound SL 81.0385. The anorectic effect of the potent serotonin uptake inhibitor SL 81.0385 was potentiated by pretreatment with 5-hydroxytryptophan and blocked by the serotonin receptor antagonist metergoline. A good correlation was obtained between the ED/sub 50/ values of anorectic action and the ED/sub 50/ values of serotonin uptake inhibition in vivo (but not in vitro) for several specific serotonin uptake inhibitors. Most of the drugs tested displaced (/sup 3/H)-mazindol from its binding to the anorectic recognition site in the hypothalamus, except the pro-drug zimelidine which was inactive. Excluding zimelidine, a good correlation was obtained between the affinities of these drugs for (/sup 3/H)-mazindol binding and their anorectic action indicating that their anorectic activity may be associated with an effect mediated through this site. Taken together these results suggest that the anorectic action of serotonin uptake inhibitors is directly associated to their ability to inhibit serotonin uptake and thus increasing the synaptic levels of serotonin. The interactions of these drugs with the anorectic recognition site labelled with (/sup 3/H)-mazindol is discussed in connection with the serotonergic regulation of carbohydrate intake.

  16. Anorectic activities of serotonin uptake inhibitors: correlation with their potencies at inhibiting serotonin uptake in vivo and 3H-mazindol binding in vitro

    International Nuclear Information System (INIS)

    Angel, I.; Taranger, M.A.; Claustre, Y.; Scatton, B.; Langer, S.Z.

    1988-01-01

    The mechanism of anorectic action of several serotonin uptake inhibitors was investigated by comparing their anorectic potencies with several biochemical and pharmacological properties and in reference to the novel compound SL 81.0385. The anorectic effect of the potent serotonin uptake inhibitor SL 81.0385 was potentiated by pretreatment with 5-hydroxytryptophan and blocked by the serotonin receptor antagonist metergoline. A good correlation was obtained between the ED 50 values of anorectic action and the ED 50 values of serotonin uptake inhibition in vivo (but not in vitro) for several specific serotonin uptake inhibitors. Most of the drugs tested displaced [ 3 H]-mazindol from its binding to the anorectic recognition site in the hypothalamus, except the pro-drug zimelidine which was inactive. Excluding zimelidine, a good correlation was obtained between the affinities of these drugs for [ 3 H]-mazindol binding and their anorectic action indicating that their anorectic activity may be associated with an effect mediated through this site. Taken together these results suggest that the anorectic action of serotonin uptake inhibitors is directly associated to their ability to inhibit serotonin uptake and thus increasing the synaptic levels of serotonin. The interactions of these drugs with the anorectic recognition site labelled with [ 3 H]-mazindol is discussed in connection with the serotonergic regulation of carbohydrate intake

  17. B2B elektroniskās komercijas potenciāls un attīstības perspektīvas Latvijā

    OpenAIRE

    Ķigule, Monta

    2012-01-01

    Bakalaura darbs „B2B elektroniskās komercijas potenciāls un attīstības perspektīvas Latvijā” mērķis ir sniegt lasītājiem priekšstatu par e-komerciju priekšrocībām uzņēmējdarbībā, un kāds ir uzņēmumu skatījums uz B2B attīstību Latvijas un uzņēmuma ietvaros. Darbs sastāv no trim galvenajām daļām. Pirmajā daļā tiek aplūkots B2B kā e-komercijas forma.. Darba otrajā daļā mēs apskatījām B2B modeļus, un tiem piemītošās īpašības un raksturu. Trešās daļas ietvaros tika apskatīti pieejamies statisti...

  18. Optimization of the antiviral potency and lipophilicity of halogenated 2,6-diarylpyridinamines as a novel class of HIV-1 NNRTIS.

    Science.gov (United States)

    Wu, Zhi-Yuan; Liu, Na; Qin, Bingjie; Huang, Li; Yu, Fei; Qian, Keduo; Morris-Natschke, Susan L; Jiang, Shibo; Chen, Chin Ho; Lee, Kuo-Hsiung; Xie, Lan

    2014-07-01

    Nineteen new halogenated diarylpyridinamine (DAPA) analogues modified at the phenoxy C-ring were synthesized and evaluated for anti-HIV activity and certain drug-like properties. Ten compounds showed high anti-HIV activity (EC50 E138K or K101E mutations, which are associated with resistance to rilvipirine (1 b). Compound 8 c exhibited much lower resistance fold changes (RFC: 1.1-2.1) than 1 b (RFC: 11.8-13.0). Compound 8 c also exhibited better metabolic stability (in vitro half-life) than 1 b in human liver microsomes, possessed low lipophilicity (clog D: 3.29; measured log P: 3.31), and had desirable lipophilic efficiency indices (LE>0.3, LLE>5, LELP<10). With balanced potency and drug-like properties, 8 c merits further development as an anti-HIV drug candidate. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Synthesis and biological evaluation of isomeric methoxy substitutions on anti-cancer indolyl-pyridinyl-propenones: Effects on potency and mode of activity.

    Science.gov (United States)

    Trabbic, Christopher J; George, Sage M; Alexander, Evan M; Du, Shengnan; Offenbacher, Jennifer M; Crissman, Emily J; Overmeyer, Jean H; Maltese, William A; Erhardt, Paul W

    2016-10-21

    Certain indolyl-pyridinyl-propenone analogues kill glioblastoma cells that have become resistant to conventional therapeutic drugs. Some of these analogues induce a novel form of non-apoptotic cell death called methuosis, while others primarily cause microtubule disruption. Ready access to 5-indole substitution has allowed characterization of this position to be important for both types of mechanisms when a simple methoxy group is present. We now report the syntheses and biological effects of isomeric methoxy substitutions on the indole ring. Additionally, analogues containing a trimethoxyphenyl group in place of the pyridinyl moiety were evaluated for anticancer activity. The results demonstrate that the location of the methoxy group can alter both the potency and the mechanism of cell death. Remarkably, changing the methoxy from the 5-position to the 6-position switched the biological activity from induction of methuosis to disruption of microtubules. The latter may represent a prototype for a new class of mitotic inhibitors with potential therapeutic utility. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. Iron Deprivation Affects Drug Susceptibilities of Mycobacteria Targeting Membrane Integrity

    Directory of Open Access Journals (Sweden)

    Rahul Pal

    2015-01-01

    Full Text Available Multidrug resistance (MDR acquired by Mycobacterium tuberculosis (MTB through continuous deployment of antitubercular drugs warrants immediate search for novel targets and mechanisms. The ability of MTB to sense and become accustomed to changes in the host is essential for survival and confers the basis of infection. A crucial condition that MTB must surmount is iron limitation, during the establishment of infection, since iron is required by both bacteria and humans. This study focuses on how iron deprivation affects drug susceptibilities of known anti-TB drugs in Mycobacterium smegmatis, a “surrogate of MTB.” We showed that iron deprivation leads to enhanced potency of most commonly used first line anti-TB drugs that could be reverted upon iron supplementation. We explored that membrane homeostasis is disrupted upon iron deprivation as revealed by enhanced membrane permeability and hypersensitivity to membrane perturbing agent leading to increased passive diffusion of drug and TEM images showing detectable differences in cell envelope thickness. Furthermore, iron seems to be indispensable to sustain genotoxic stress suggesting its possible role in DNA repair machinery. Taken together, we for the first time established a link between cellular iron and drug susceptibility of mycobacteria suggesting iron as novel determinant to combat MDR.

  1. Gene duplication and divergence affecting drug content in Cannabis sativa.

    Science.gov (United States)

    Weiblen, George D; Wenger, Jonathan P; Craft, Kathleen J; ElSohly, Mahmoud A; Mehmedic, Zlatko; Treiber, Erin L; Marks, M David

    2015-12-01

    Cannabis sativa is an economically important source of durable fibers, nutritious seeds, and psychoactive drugs but few economic plants are so poorly understood genetically. Marijuana and hemp were crossed to evaluate competing models of cannabinoid inheritance and to explain the predominance of tetrahydrocannabinolic acid (THCA) in marijuana compared with cannabidiolic acid (CBDA) in hemp. Individuals in the resulting F2 population were assessed for differential expression of cannabinoid synthase genes and were used in linkage mapping. Genetic markers associated with divergent cannabinoid phenotypes were identified. Although phenotypic segregation and a major quantitative trait locus (QTL) for the THCA/CBDA ratio were consistent with a simple model of codominant alleles at a single locus, the diversity of THCA and CBDA synthase sequences observed in the mapping population, the position of enzyme coding loci on the map, and patterns of expression suggest multiple linked loci. Phylogenetic analysis further suggests a history of duplication and divergence affecting drug content. Marijuana is distinguished from hemp by a nonfunctional CBDA synthase that appears to have been positively selected to enhance psychoactivity. An unlinked QTL for cannabinoid quantity may also have played a role in the recent escalation of drug potency. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  2. Material and Affective Movements

    DEFF Research Database (Denmark)

    Rasmussen, Lisa Rosén

    2014-01-01

    This chapter offers a study of life at school as remembered by groups of people who finished secondary school in the 1950s, 1970s and 1990s. The article draws up three generational portraits based on in-depth interviews that demonstrate how school life is remembered in complex and textural ways. ...... the use of spoken memories is a rewarding source for the writing about school from the pupils’ perspective........ The chapter traces the former pupil’s memories of physical and affective movements within the larger context of school and discovers surprisingly diverse modes of knowing, relating, and attending to things, teachers and classmates among and between the three generations. It thus taps into the rich realms...

  3. Multisensory Perception of Affect

    Directory of Open Access Journals (Sweden)

    Beatrice de Gelder

    2011-10-01

    Full Text Available Multisensory integration must stand out among the fields of research that have witnessed a most impressive explosion of interest this last decade. One of these new areas of multisensory research concerns emotion. Since our first exploration of this phenomenon (de Gelder et al., 1999 a number of studies have appeared and they have used a wide variety of behavioral, neuropsychological and neuroscientifc methods. The goal of this presentation is threefold. First, we review the research on audiovisual perception of emotional signals from the face and the voice followed by a report or more recent studies on integrating emotional information provided by the voice and whole body expressions. We will also include some recent work on multisensory music perception. In the next section we discuss some methodological and theoretical issues. Finally, we will discuss findings about abnormal affective audiovisual integration in schizophrenia and in autism.

  4. Trauma-affected refugees

    DEFF Research Database (Denmark)

    Sonne, Charlotte Kærgaard

    2016-01-01

    treatment outcome for this patient group. Methods: This thesis includes four papers based on two studies – a literature review and a randomised trial called PTF3: The aim of the literature review was to provide an overview of the existing literature on the pharmacological treatment of refugees with PTSD and....... The aim of PTF3 was to examine differences in the effects of venlafaxine and sertraline on Post-traumatic Stress Disorder (PTSD), depression and functional impairments in trauma-affected refugees as well as research predictors for treatment outcome. The patients included were 207 adult refugees diagnosed...... with PTSD and/or depression who had their first appointment at Competence Centre for Transcultural Psychiatry (CTP) between April 1st 2012 and September 16th 2013. Patients were randomised into one of the two treatment groups: a sertraline group (n=109) or a venlafaxine group (n=98). Patients in both groups...

  5. Affective World Literature

    DEFF Research Database (Denmark)

    Vilslev, Annette Thorsen

    The PhD dissertation compares the literary theory and novels of modern Japanese writer Natsume Sōseki. It reads Sōseki’s Theory of Literature (2009, Bungakuron, 1907) as an inherently comparative and interdisciplinary approach to theorizing feelings in world literature. More broadly, the disserta......The PhD dissertation compares the literary theory and novels of modern Japanese writer Natsume Sōseki. It reads Sōseki’s Theory of Literature (2009, Bungakuron, 1907) as an inherently comparative and interdisciplinary approach to theorizing feelings in world literature. More broadly......, the dissertation investigates the critical negotiation of the novel as a travelling genre in Japan in the beginning of the 20th century, and, more specifically, Sōseki’s work in relation to world literature and affect theory. Sōseki’s work is highly influential in Japan and East Asia, and his novels widely...

  6. Factors Affecting Wound Healing

    Science.gov (United States)

    Guo, S.; DiPietro, L.A.

    2010-01-01

    Wound healing, as a normal biological process in the human body, is achieved through four precisely and highly programmed phases: hemostasis, inflammation, proliferation, and remodeling. For a wound to heal successfully, all four phases must occur in the proper sequence and time frame. Many factors can interfere with one or more phases of this process, thus causing improper or impaired wound healing. This article reviews the recent literature on the most significant factors that affect cutaneous wound healing and the potential cellular and/or molecular mechanisms involved. The factors discussed include oxygenation, infection, age and sex hormones, stress, diabetes, obesity, medications, alcoholism, smoking, and nutrition. A better understanding of the influence of these factors on repair may lead to therapeutics that improve wound healing and resolve impaired wounds. PMID:20139336

  7. Anticipated affect and behavioral choice

    NARCIS (Netherlands)

    Richard, R.; van der Pligt, J.; de Vries, N.K.

    1996-01-01

    Most research on the impact of affect on attitudes and behavior emphasizes the effect of past and present affective reactions. In this article we focus on anticipated, postbehavioral, affective reactions. The influence of anticipated affective reactions on a number of behaviors was investigated in

  8. Security affects us all!

    CERN Multimedia

    SMB Department

    2016-01-01

    In the hope of minimising the number of thefts of the Organization’s property, which can lead to months of work going to waste on certain projects, you are reminded of the importance that CERN attaches to the rules concerning the protection of equipment for which we are responsible. If you see any unusual behaviour or if you are the victim of a theft, don’t hesitate to report it by submitting a ticket through the CERN Portal or calling the CSA. Security affects us all!   CERN is attractive in more ways than one, and it remains as attractive as ever to thieves. With the nice weather and with the holiday season in full swing, the number of thefts recorded at CERN is on the rise. Items stolen include money, computers, electronic equipment, cable drums and copper antennae.   There are a few basic precautions that you should take to protect both your own and the Organization’s property: lock your door, don’t leave valuable items in your office, st...

  9. Affective World Literature

    DEFF Research Database (Denmark)

    Vilslev, Annette Thorsen

    The PhD dissertation compares the literary theory and novels of modern Japanese writer Natsume Sōseki. It reads Sōseki’s Theory of Literature (2009, Bungakuron, 1907) as an inherently comparative and interdisciplinary approach to theorizing feelings in world literature. More broadly, the disserta......The PhD dissertation compares the literary theory and novels of modern Japanese writer Natsume Sōseki. It reads Sōseki’s Theory of Literature (2009, Bungakuron, 1907) as an inherently comparative and interdisciplinary approach to theorizing feelings in world literature. More broadly......, the dissertation investigates the critical negotiation of the novel as a travelling genre in Japan in the beginning of the 20th century, and, more specifically, Sōseki’s work in relation to world literature and affect theory. Sōseki’s work is highly influential in Japan and East Asia, and his novels widely...... circulated beyond Japan. Using Sōseki’s theory as an example, and by comparing it to other theories, the dissertation argues that comparative literature needs to include not only more non-Western literature but also more non-Western literary theories in the ongoing debate of world literature. Close...

  10. How chain length and charge affect surfactant denaturation of acyl coenzyme a binding protein (ACBP)

    DEFF Research Database (Denmark)

    Andersen, Kell; Otzen, Daniel

    2009-01-01

    Using intrinsic tryptophan fluorescence, equilibria and kinetics of unfolding of acyl coenzyme A binding protein (ACBP) have been investigated in sodium alkyl sulfate surfactants of different chain length (8-16 carbon atoms) and with different proportions of the nonionic surfactant dodecyl...... maltoside (DDM). The aim has been to determine how surfactant chain length and micellar charge affect the denaturation mechanism. ACBP denatures in two steps irrespective of surfactant chain length, but with increasing chain length, the potency of the denaturant rises more rapidly than the critical micelle...... constants increases linearly with denaturant concentration below the cmc but declines at higher concentrations. Both shortening chain length and decreasing micellar charge reduce the overall kinetics of unfolding and makes the dependence of unfolding rate constants on surfactant concentration more complex...

  11. Affective match: Leader emotions, follower positive affect, and follower performance

    NARCIS (Netherlands)

    Damen, F.; van Knippenberg, B.M.; van Knippenberg, D.

    2008-01-01

    Leader emotions may play an important role in leadership effectiveness. Extending earlier research on leader emotional displays and leadership effectiveness, we propose that the affective match between follower positive affect (PA) and leaders' emotional displays moderates the effectiveness of

  12. Antihistamines suppress upregulation of histidine decarboxylase gene expression with potencies different from their binding affinities for histamine H1 receptor in toluene 2,4-diisocyanate-sensitized rats

    Directory of Open Access Journals (Sweden)

    Hiroyuki Mizuguchi

    2016-04-01

    Full Text Available Antihistamines inhibit histamine signaling by blocking histamine H1 receptor (H1R or suppressing H1R signaling as inverse agonists. The H1R gene is upregulated in patients with pollinosis, and its expression level is correlated with the severity of nasal symptoms. Here, we show that antihistamine suppressed upregulation of histidine decarboxylase (HDC mRNA expression in patients with pollinosis, and its expression level was correlated with that of H1R mRNA. Certain antihistamines, including mepyramine and diphenhydramine, suppress toluene-2,4-diisocyanate (TDI-induced upregulation of HDC gene expression and increase HDC activity in TDI-sensitized rats. However, d-chlorpheniramine did not demonstrate any effect. The potencies of antihistamine suppressive effects on HDC mRNA elevation were different from their H1R receptor binding affinities. In TDI-sensitized rats, the potencies of antihistamine inhibitory effects on sneezing in the early phase were related to H1R binding. In contrast, the potencies of their inhibitory effects on sneezing in the late phase were correlated with those of suppressive effects on HDC mRNA elevation. Data suggest that in addition to the antihistaminic and inverse agonistic activities, certain antihistamines possess additional properties unrelated to receptor binding and alleviate nasal symptoms in the late phase by inhibiting synthesis and release of histamine by suppressing HDC gene transcription.

  13. Antihistamines suppress upregulation of histidine decarboxylase gene expression with potencies different from their binding affinities for histamine H1 receptor in toluene 2,4-diisocyanate-sensitized rats.

    Science.gov (United States)

    Mizuguchi, Hiroyuki; Das, Asish K; Maeyama, Kazutaka; Dev, Shrabanti; Shahriar, Masum; Kitamura, Yoshiaki; Takeda, Noriaki; Fukui, Hiroyuki

    2016-04-01

    Antihistamines inhibit histamine signaling by blocking histamine H1 receptor (H1R) or suppressing H1R signaling as inverse agonists. The H1R gene is upregulated in patients with pollinosis, and its expression level is correlated with the severity of nasal symptoms. Here, we show that antihistamine suppressed upregulation of histidine decarboxylase (HDC) mRNA expression in patients with pollinosis, and its expression level was correlated with that of H1R mRNA. Certain antihistamines, including mepyramine and diphenhydramine, suppress toluene-2,4-diisocyanate (TDI)-induced upregulation of HDC gene expression and increase HDC activity in TDI-sensitized rats. However, d-chlorpheniramine did not demonstrate any effect. The potencies of antihistamine suppressive effects on HDC mRNA elevation were different from their H1R receptor binding affinities. In TDI-sensitized rats, the potencies of antihistamine inhibitory effects on sneezing in the early phase were related to H1R binding. In contrast, the potencies of their inhibitory effects on sneezing in the late phase were correlated with those of suppressive effects on HDC mRNA elevation. Data suggest that in addition to the antihistaminic and inverse agonistic activities, certain antihistamines possess additional properties unrelated to receptor binding and alleviate nasal symptoms in the late phase by inhibiting synthesis and release of histamine by suppressing HDC gene transcription. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  14. Non-coding RNAs in Mesenchymal Stem Cell-Derived Extracellular Vesicles: Deciphering Regulatory Roles in Stem Cell Potency, Inflammatory Resolve, and Tissue Regeneration

    Science.gov (United States)

    Fatima, Farah; Ekstrom, Karin; Nazarenko, Irina; Maugeri, Marco; Valadi, Hadi; Hill, Andrew F.; Camussi, Giovanni; Nawaz, Muhammad

    2017-01-01

    Extracellular vesicles (EVs) are heterogeneous populations of nano- and micro-sized vesicles secreted by various cell types. There is mounting evidence that EVs have widespread roles in transporting proteins, lipids, and nucleic acids between cells and serve as mediators of intercellular communication. EVs secreted from stem cells could function as paracrine factors, and appear to mimic and recapitulate several features of their secreting cells. EV-mediated transport of regulatory RNAs provides a novel source of trans-regulation between cells. As such, stem cells have evolved unique forms of paracrine mechanisms for recapitulating their potencies with specialized functions by transporting non-coding RNAs (ncRNAs) via EVs. This includes the dissemination of stem cell-derived EV-ncRNAs and their regulatory effects elicited in differentiation, self-renewal, pluripotency, and the induction of reparative programs. Here, we summarize and discuss the therapeutic effects of mesenchymal stem cell-derived EV-ncRNAs in the induction of intrinsic regenerative programs elicited through regulating several mechanisms. Among them, most noticeable are the EV-mediated enrichment of ncRNAs at the injury sites contributing the regulation of matrix remodeling, epithelial mesenchymal transitions, and attraction of fibroblasts. Additionally, we emphasize EV-mediated transmission of anti-inflammatory RNAs from stem cells to injury site that potentially orchestrate the resolution of the inflammatory responses and immune alleviation to better facilitate healing processes. Collectively, this knowledge indicates a high value and potential of EV-mediated RNA-based therapeutic approaches in regenerative medicine. PMID:29123544

  15. Stereoselective Blockage of Quinidine and Quinine in the hERG Channel and the Effect of Their Rescue Potency on Drug-Induced hERG Trafficking Defect

    Directory of Open Access Journals (Sweden)

    Meng Yan

    2016-09-01

    Full Text Available Diastereoisomers of quinidine and quinine are used to treat arrhythmia and malaria, respectively. It has been reported that both drugs block the hERG (human ether-a-go-go-related gene potassium channel which is essential for myocardium repolarization. Abnormality of repolarization increases risk of arrhythmia. The aim of our research is to study and compare the impacts of quinidine and quinine on hERG. Results show that both drugs block the hERG channel, with quinine 14-fold less potent than quinidine. In addition, they presented distinct impacts on channel dynamics. The results imply their stereospecific block effect on the hERG channel. However, F656C-hERG reversed this stereoselectivity. The mutation decreases affinity of the two drugs with hERG, and quinine was more potent than quinidine in F656C-hERG blockage. These data suggest that F656 residue contributes to the stereoselective pocket for quinidine and quinine. Further study demonstrates that both drugs do not change hERG protein levels. In rescue experiments, we found that they exert no reverse effect on pentamidine- or desipramine-induced hERG trafficking defect, although quinidine has been reported to rescue trafficking-deficient pore mutation hERG G601S based on the interaction with F656. Our research demonstrated stereoselective effects of quinidine and quinine on the hERG channel, and this is the first study to explore their reversal potency on drug-induced hERG deficiency.

  16. Potency determination of follitropin, lutropin And thyrotropin: a comparison between the quantification by reversed-phase high-performance liquid chromatography and in vivo bioassay

    International Nuclear Information System (INIS)

    Almeida, Beatriz Elane de

    2013-01-01

    With the intention of setting up physico-chemical methods as an alternative to in vivo bioassay for determining biological activity, the hFSH, hTSH and hLH content of native and recombinant preparations was determined by reversed-phase high-performance liquid chromatography (RP-HPLC) and compared with the data obtained by the classical mouse or rat in vivo bioassays (BA). A linear relationship between the two methods was found for these hormones: hFSH BA U= 0.9925 RP-HPLC U– 1.3165, r = 0.9371, p IU = 0.8771 RP-HPLC IU + 12.41, r = 0.9786, p < 0.01, n = 5. For nine other hFSH and eleven hTSH preparations, the mean difference ( ) between the bioactivity predicted from RP-HPLC data via these equations and the mean of the bioactivities obtained with the two methods was as follows. For hLH this difference could not be estimated due to lack of different samples. In the case of hFSH, ± SD = -2.11 ± 3.49% with a precision of 1.16% and in the case of hTSH, ± SD = -2.01 ± 5.56 %, with precision of 1.68%. Partly-degraded hFSH, hTSH and hLH samples presented different activity degrees that could be predicted by RP-HPLC, with an acceptable agreement with the in vivo bioassays. These results demonstrate that the employment of a non-animal physico-chemical assay, such as RP-HPLC, is a viable alternative to the use of an in vivo bioassay for hFSH and hTSH potency determination, thus reducing the number of animals currently used for assuring quality and efficacy of a pharmaceutical product. (author)

  17. Unexpected Potency Differences between B-Cell-Activating Factor (BAFF) Antagonist Antibodies against Various Forms of BAFF: Trimer, 60-Mer, and Membrane-Bound.

    Science.gov (United States)

    Nicoletti, Amy M; Kenny, Cynthia Hess; Khalil, Ashraf M; Pan, Qi; Ralph, Kerry L M; Ritchie, Julie; Venkataramani, Sathyadevi; Presky, David H; DeWire, Scott M; Brodeur, Scott R

    2016-10-01

    Therapeutic agents antagonizing B-cell-activating factor/B-lymphocyte stimulator (BAFF/BLyS) are currently in clinical development for autoimmune diseases; belimumab is the first Food and Drug Administration-approved drug in more than 50 years for the treatment of lupus. As a member of the tumor necrosis factor superfamily, BAFF promotes B-cell survival and homeostasis and is overexpressed in patients with systemic lupus erythematosus and other autoimmune diseases. BAFF exists in three recognized forms: membrane-bound and two secreted, soluble forms of either trimeric or 60-mer oligomeric states. To date, most in vitro pharmacology studies of BAFF neglect one or more of these forms. Here, we report a comprehensive in vitro cell-based analysis of BAFF in assay systems that measure all forms of BAFF-mediated activation. We demonstrate the effects of these BAFF forms in both a primary human B-cell proliferation assay and in nuclear factor κB reporter assay systems in Chinese hamster ovary cells expressing BAFF receptors and transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI). In contrast to the mouse system, we find that BAFF trimer activates the human TACI receptor. Further, we profiled the activities of two clinically advanced BAFF antagonist antibodies, belimumab and tabalumab. Unexpectedly, we revealed differences in inhibitory potencies against the various BAFF forms, in particular that belimumab does not potently inhibit BAFF 60-mer. Through this increased understanding of the activity of BAFF antagonists against different forms of BAFF, we hope to influence the discovery of BAFF antagonist antibodies with distinct therapeutic mechanisms for improvement in the treatment of lupus or other related autoimmune pathologies. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  18. A significantly lower potency observed for the 3rd WHO International Standard for Parvovirus B19V DNA with the cobas TaqScreen DPX test.

    Science.gov (United States)

    Pisani, G; Cristiano, K; Fabi, S; Simeoni, M; Marino, F; Gaggioli, A

    2016-08-01

    In the context of the Official Medicines Control Laboratories plasma pool testing for Parvovirus B19 DNA, we use the cobas TaqScreen DPX test. When we re-evaluated this method using the 3rd B19 DNA WHO IS at the final concentration of 4 log IU/mL, we observed a titre lower than expected, i.e. 3.79 log IU/mL. Therefore, we further investigated the accuracy of the DPX test. The following B19V DNA materials were tested by using both the DPX test and an in-house real-time PCR: The 1st, 2nd and 3rd WHO ISs for B19V DNA The Non WHO B19V DNA Reference Material for NAT The Biological Reference Preparation B19 virus DNA for NAT testing, batch 1 . The DPX test showed a good accuracy for all B19V DNA materials with the exception of the 3rd WHO IS for B19V DNA. In fact, an underestimation of about 38% was observed for all dilutions of this standard with respect to the nominal titre. With the B19V in-house real-time PCR, all four materials proved to be well calibrated against the 1(st) WHO IS for B19V DNA, used as external standard curve. In this study, we demonstrated that the DPX test underestimates the B19V DNA content of the 3rd WHO IS for B19V DNA and that this is not due to an incorrect potency assigned to the standard but, most probably, to a mismatch between the primers/probe and the sequence of the target region in the 3rd WHO IS for B19V DNA. © 2016 International Society of Blood Transfusion.

  19. Potency of Bacillus thuringiensis isolates from bareng Tenes-Malang City as a biological control agent for suppressing third instar of Aedes aegypti larvae

    Science.gov (United States)

    Lutfiana, Nihayatul; Gama, Zulfaidah Penata

    2017-11-01

    Dengue is a mosquito-borne viral disease that is transmitted by the female Aedes species. The number of dengue fever cases has increased in many geographic regions including Indonesia and one of them occurred in Bareng Tenes, Malang City, East Java Province. The objective of this research was to identify the potency of B. thuringeinsis isolates from Bareng Tenes, Malang, as the biological agent to control third instar Ae. aegypti larvae and to identify the potential B. thuringiensis isolates based on 16S rDNA sequence. B. thuringiensis was isolated from water and soil from 12 sites in the Bareng Tenes area. Bacterial isolation was performed using B. thuringiensis selective media. Several isolates had similar phenotypic characters with B. thuringiensis used to toxicity test against third instar Ae. aegypti larvae. The LC50-96h value was determined using probit regression. The most effective isolate was identified based on the 16S rDNA sequence, then aligned to the reference isolate using the BLAST program. A phylogeny tree was constructed using the Maximum Likelihood method. This study showed that among 22 isolates of B. thuringiensis, only BA02b, BS04a, and BA03a isolates have similar phenotypic characters with B. thuringiensis. Based on the toxicity test of B. thuringiensis against the third instar of Ae. aegypti larvae, it was indicated that BA02b and BA03a isolates were the potential agents to control Ae. aegypti larvae. BA02b isolate was the most effective B. thuringiensis (LC50-96h = 2,75 x 107 cell/mL). Based on 16S rDNA sequence, BA02b was identified as Bacillus thuringiensis var. Israelensis BGSC4Q2 (99 % similarities).

  20. Gemcitabine-(5'-phosphoramidate)-[anti-IGF-1R]: molecular design, synthetic organic chemistry reactions, and antineoplastic cytotoxic potency in populations of pulmonary adenocarcinoma (A549).

    Science.gov (United States)

    Coyne, Cody P; Narayanan, Lakshmi

    2017-03-01

    One molecular-based approach that increases potency and reduces dose-limited sequela is the implementation of selective 'targeted' delivery strategies for conventional small molecular weight chemotherapeutic agents. Descriptions of the molecular design and organic chemistry reactions that are applicable for synthesis of covalent gemcitabine-monophosphate immunochemotherapeutics have to date not been reported. The covalent immunopharmaceutical, gemcitabine-(5'-phosphoramidate)-[anti-IGF-1R] was synthesized by reacting gemcitabine with a carbodiimide reagent to form a gemcitabine carbodiimide phosphate ester intermediate which was subsequently reacted with imidazole to create amine-reactive gemcitabine-(5'-phosphorylimidazolide) intermediate. Monoclonal anti-IGF-1R immunoglobulin was combined with gemcitabine-(5'-phosphorylimidazolide) resulting in the synthetic formation of gemcitabine-(5'-phosphoramidate)-[anti-IGF-1R]. The gemcitabine molar incorporation index for gemcitabine-(5'-phosphoramidate)-[anti-IGF-R1] was 2.67:1. Cytotoxicity Analysis - dramatic increases in antineoplastic cytotoxicity were observed at and between the gemcitabine-equivalent concentrations of 10 -9  M and 10 -7  M where lethal cancer cell death increased from 0.0% to a 93.1% maximum (100.% to 6.93% residual survival), respectively. Advantages of the organic chemistry reactions in the multistage synthesis scheme for gemcitabine-(5'-phosphoramidate)-[anti-IGF-1R] include their capacity to achieve high chemotherapeutic molar incorporation ratios; option of producing an amine-reactive chemotherapeutic intermediate that can be preserved for future synthesis applications; and non-dedicated organic chemistry reaction scheme that allows substitutions of either or both therapeutic moieties, and molecular delivery platforms. © 2016 The Authors Chemical Biology & Drug Design Published by John Wiley & Sons Ltd.