Fate of Escherichia coli O157:H7 and bacterial diversity in corn silage contaminated with the pathogen and treated with chemical or microbial additives.

PubMed

Ogunade, I M; Jiang, Y; Kim, D H; Cervantes, A A Pech; Arriola, K G; Vyas, D; Weinberg, Z G; Jeong, K C; Adesogan, A T

2017-03-01

Inhibiting the growth of Escherichia coli O157:H7 (EC) in feeds may prevent the transmission or cycling of the pathogen on farms. The first objective of this study was to examine if addition of propionic acid or microbial inoculants would inhibit the growth of EC during ensiling, at silo opening, or after aerobic exposure. The second objective was to examine how additives affected the bacterial community composition in corn silage. Corn forage was harvested at approximately 35% dry matter, chopped to a theoretical length of cut of 10 mm, and ensiled after treatment with one of the following: (1) distilled water (control); (2) 1 × 10 5 cfu/g of EC (ECCH); (3) EC and 1 × 10 6 cfu/g of Lactobacillus plantarum (ECLP); (4) EC and 1 × 10 6 cfu/g of Lactobacillus buchneri (ECLB); and (5) EC and 2.2 g/kg (fresh weight basis) of propionic acid, containing 99.5% of the acid (ECA). Each treatment was ensiled in quadruplicate in laboratory silos for 0, 3, 7, and 120 d and analyzed for EC, pH, and organic acids. Samples from d 0 and 120 were also analyzed for chemical composition. Furthermore, samples from d 120 were analyzed for ammonia N, yeasts and molds, lactic acid bacteria, bacterial community composition, and aerobic stability. The pH of silages from all treatments decreased below 4 within 3 d of ensiling. Escherichia coli O157:H7 counts were below the detection limit in all silages after 7 d of ensiling. Treatment with L. buchneri and propionic acid resulted in fewer yeasts and greater aerobic stability compared with control, ECCH, and ECLP silages. Compared with the control, the diversity analysis revealed a less diverse bacterial community in the ECLP silage and greater abundance of Lactobacillus in the ECLP and ECA silages. The ECLB silage also contained greater abundance of Acinetobacter and Weissella than other silages. Subsamples of silages were reinoculated with 5 × 10 5 cfu/g of EC either immediately after silo opening or after 168 h of aerobic exposure, and EC were enumerated after 6 or 24 h, respectively. All silages reinoculated with EC immediately after silo opening (120 h) had similar low pH values (<4.0) and EC counts were below the detection limit. The ECCH and ECLP silages reinoculated with EC after 168 h of aerobic exposure had relatively high pH values (>5.0) and EC counts (5.39 and 5.30 log cfu/g, respectively) 24 h later. However, those treated with L. buchneri or propionic acid had lower pH values (4.24 or 3.96, respectively) and lower EC counts (1.32 log cfu/g or none, respectively). During ensiling, EC was eliminated from all silages at pH below 4.0. During aerobic exposure, the growth of EC was reduced or prevented in silages that had been treated with L. buchneri or propionic acid at ensiling, respectively. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Tolerance of anaerobic bacteria to chlorinated solvents.

PubMed

Koenig, Joanna C; Groissmeier, Kathrin D; Manefield, Mike J

2014-01-01

The aim of this research was to evaluate the effects of four chlorinated aliphatic hydrocarbons (CAHs), perchloroethene (PCE), carbon tetrachloride (CT), chloroform (CF) and 1,2-dichloroethane (1,2-DCA), on the growth of eight anaerobic bacteria: four fermentative species (Escherichia coli, Klebsiella sp., Clostridium sp. and Paenibacillus sp.) and four respiring species (Pseudomonas aeruginosa, Geobacter sulfurreducens, Shewanella oneidensis and Desulfovibrio vulgaris). Effective concentrations of solvents which inhibited growth rates by 50% (EC50) were determined. The octanol-water partition coefficient or log Po/w of a CAH proved a generally satisfactory measure of its toxicity. Most species tolerated approximately 3-fold and 10-fold higher concentrations of the two relatively more polar CAHs CF and 1,2-DCA, respectively, than the two relatively less polar compounds PCE and CT. EC50 values correlated well with growth rates observed in solvent-free cultures, with fast-growing organisms displaying higher tolerance levels. Overall, fermentative bacteria were more tolerant to CAHs than respiring species, with iron- and sulfate-reducing bacteria in particular appearing highly sensitive to CAHs. These data extend the current understanding of the impact of CAHs on a range of anaerobic bacteria, which will benefit the field of bioremediation.

Tolerance of Anaerobic Bacteria to Chlorinated Solvents

PubMed Central

Koenig, Joanna C.; Groissmeier, Kathrin D.; Manefield, Mike J.

2014-01-01

The aim of this research was to evaluate the effects of four chlorinated aliphatic hydrocarbons (CAHs), perchloroethene (PCE), carbon tetrachloride (CT), chloroform (CF) and 1,2-dichloroethane (1,2-DCA), on the growth of eight anaerobic bacteria: four fermentative species (Escherichia coli, Klebsiella sp., Clostridium sp. and Paenibacillus sp.) and four respiring species (Pseudomonas aeruginosa, Geobacter sulfurreducens, Shewanella oneidensis and Desulfovibrio vulgaris). Effective concentrations of solvents which inhibited growth rates by 50% (EC50) were determined. The octanol-water partition coefficient or log Po/w of a CAH proved a generally satisfactory measure of its toxicity. Most species tolerated approximately 3-fold and 10-fold higher concentrations of the two relatively more polar CAHs CF and 1,2-DCA, respectively, than the two relatively less polar compounds PCE and CT. EC50 values correlated well with growth rates observed in solvent-free cultures, with fast-growing organisms displaying higher tolerance levels. Overall, fermentative bacteria were more tolerant to CAHs than respiring species, with iron- and sulfate-reducing bacteria in particular appearing highly sensitive to CAHs. These data extend the current understanding of the impact of CAHs on a range of anaerobic bacteria, which will benefit the field of bioremediation. PMID:24441515

[Diagnostic values of salivary versus and plasma microRNA-21 for early esophageal cancer].

PubMed

Ye, Minhua; Ye, Penghui; Zhang, Weizhu; Rao, Jiaqi; Xie, Zijun

2014-06-01

To evaluate the diagnostic value of salivary and plasma miR-21 in patients with esophageal cancer (EC). Total RNA was extracted from saliva and plasma samples from 50 stage I and 50 stage II patients with EC and 50 healthy controls for measurement of miR-21 levels using qPCR. The diagnostic values of salivary and plasma miR-21 levels were assessed for stage I, stage II, and stage I+II EC. Salivary and plasma miR-21 were significantly higher in the EC patients than in the control group. The diagnostic sensitivities of plasma miR-21 for stage I, stage II, and stage I+II EC were 96%, 64% and 97%, with specificities of 44%, 84%, and 56%, respectively; the sensitivities of salivary miR-21 were 90%, 88%, and 89%, respectively, with the same specificities of 64%. Regardless of EC staging, the expression of plasma miR-21 showed a significant positive correlation with that of salivary miR-21, and their diagnostic values were comparable. Both salivary and plasmatic miR-21 can be sensitive biomarkers for EC, and salivary miR-21 detection has the potential to replace plasma detection for EC diagnosis.

Shear-wave seismic reflection imaging and impedance inversion for a near-surface point-bar

NASA Astrophysics Data System (ADS)

Benton, N. W.; Morrison, M.; Lorenzo, J. M.; Odom, B.; Clift, P. D.; Olson, E.; Gostic, A.

2017-12-01

Imaging and inversion of SH-waves are useful to detect, map, and quantitatively characterize near-surface point-bar strata. We conduct a horizontally-polarized (SH) reflection survey across and along a near-surface (9 - 40 m) downstream point-bar. We invert for shear-impedance profiles and correlate our interpretation to electrical conductivity (EC) logs in adjacent wells to study the internal architecture and lithology of point-bars. We acquire two common-midpoint (CMP) SH-wave seismic reflection lines at False River (Point Coupee Parish, Louisiana). A 104 m long seismic line (L1) is oriented orthogonal (NW - SE) to point-bar strike. A second line (L2) is 48 m long and set parallel to point-bar strike (NE - SW). Two EC wells lie 33 m apart. Both wells are parallel with respect to the L1 survey and offset from it by 15 m. EC log measurements range from 1 - 25 m depth. Interference of Love-waves prevents seismic imaging at depths less than 9 m. The L1 and L2 data sets are inverted for shear-impedance using a model-based band-limited impedance (BLIMP) algorithm that incorporates a low-frequency velocity model. This model is also used for the depthing processing. The L1 cross-section shows coherent dipping reflection events ( 4 - 7º) from 0.15 - 0.35 s (10 - 40 m). The corresponding shear-impedance profile also reveals coherent and dipping impedance contrasts that grow in magnitude with increasing depth. The L2 cross-section shows comparatively less dip ( 1º) as well as sharper and shallower continuity of reflection events (0.1 - 0.28 s TWT or 9 - 25 m). Depth-converted (TVD) seismic amplitudes and impedance values correlate to near-surface point-bar geology via superposition of log data. The first well (W5) shows distinct EC local maxima (+50 - 70 mS/m) at 14.5 and 15.5 m depth that correlate well with the seismic amplitudes and impedance values from both L1 and L2 data sets. The second well (W7) shows comparatively lower local maxima (+40 - 60 mS/m) but at greater depths (15.5 and 16.5 m). W5 correlates better with the seismic cross-section and impedance profile from L2 at 10, 12.5, 14.5, 15.5, and 19 m depth. EC maxima align with distinct shear-impedance values for L1 and L2 profiles. Our results provide a new and useful perspective of remotely analyzing the architecture and lithological properties of near-surface point-bars.

The guinea pig ileum lacks the direct, high-potency, M(2)-muscarinic, contractile mechanism characteristic of the mouse ileum.

PubMed

Griffin, Michael T; Matsui, Minoru; Ostrom, Rennolds S; Ehlert, Frederick J

2009-10-01

We explored whether the M(2) muscarinic receptor in the guinea pig ileum elicits a highly potent, direct-contractile response, like that from the M(3) muscarinic receptor knockout mouse. First, we characterized the irreversible receptor-blocking activity of 4-DAMP mustard in ileum from muscarinic receptor knockout mice to verify its M(3) selectivity. Then, we used 4-DAMP mustard to inactivate M(3) responses in the guinea pig ileum to attempt to reveal direct, M(2) receptor-mediated contractions. The muscarinic agonist, oxotremorine-M, elicited potent contractions in ileum from wild-type, M(2) receptor knockout, and M(3) receptor knockout mice characterized by negative log EC(50) (pEC (50)) values +/- SEM of 6.75 +/- 0.03, 6.26 +/- 0.05, and 6.99 +/- 0.08, respectively. The corresponding E (max) values in wild-type and M(2) receptor knockout mice were approximately the same, but that in the M(3) receptor knockout mouse was only 36% of wild type. Following 4-DAMP mustard treatment, the concentration-response curve of oxotremorine-M in wild-type ileum resembled that of the M(3) knockout mouse in terms of its pEC (50), E (max), and inhibition by selective muscarinic antagonists. Thus, 4-DAMP mustard treatment appears to inactivate M(3) responses selectively and renders the muscarinic contractile behavior of the wild-type ileum similar to that of the M(3) knockout mouse. Following 4-DAMP mustard treatment, the contractile response of the guinea pig ileum to oxotremorine-M exhibited low potency and a competitive-antagonism profile consistent with an M(3) response. The guinea pig ileum, therefore, lacks a direct, highly potent, M(2)-contractile component but may have a direct, lower potency M(2) component.

High-precision Q EC values of superallowed 0 + → 0 + β-emitters 46Cr, 50Fe and 54Ni

DOE PAGES

Zhang, P.; Xu, X.; Shuai, P.; ...

2017-01-23

Short-lived 46Cr, 50Fe and 54Ni were studied by isochronous mass spectrometry at the HIRFL-CSR facility in Lanzhou. The measured precision mass excesses (ME) of 46Cr, 50Fe and 54Ni are -29471(11) keV, -34477(6) keV and -39278(4) keV, respectively. The superallowed 0 +→0+β-decay Q values were derived to be Q EC( 46Cr) =7604(11) keV, Q EC( 50Fe) =8150(6) keV and Q EC( 54Ni) =8731(4) keV. The values for 50Fe and 54Ni are by one order of magnitude more precise than the adopted literature values. By combining the existing half-lives and branching ratios, we obtained the corrected ℱt values to be ℱt(more » 50Fe) =3103(70) s and ℱt( 54Ni) =3076(50) s. The main contribution to the ℱt uncertainties is now due to β-decay branching ratios, still, more high-precision measurements of the half-lives, the masses, and especially the branching ratios are needed in order to satisfy the requirements for a stringent CVC test.« less

High-precision Q EC values of superallowed 0 + → 0 + β-emitters 46Cr, 50Fe and 54Ni

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, P.; Xu, X.; Shuai, P.

Short-lived 46Cr, 50Fe and 54Ni were studied by isochronous mass spectrometry at the HIRFL-CSR facility in Lanzhou. The measured precision mass excesses (ME) of 46Cr, 50Fe and 54Ni are -29471(11) keV, -34477(6) keV and -39278(4) keV, respectively. The superallowed 0 +→0+β-decay Q values were derived to be Q EC( 46Cr) =7604(11) keV, Q EC( 50Fe) =8150(6) keV and Q EC( 54Ni) =8731(4) keV. The values for 50Fe and 54Ni are by one order of magnitude more precise than the adopted literature values. By combining the existing half-lives and branching ratios, we obtained the corrected ℱt values to be ℱt(more » 50Fe) =3103(70) s and ℱt( 54Ni) =3076(50) s. The main contribution to the ℱt uncertainties is now due to β-decay branching ratios, still, more high-precision measurements of the half-lives, the masses, and especially the branching ratios are needed in order to satisfy the requirements for a stringent CVC test.« less

Antiviral Evaluation of Octadecyloxyethyl Esters of (S)-3-Hydroxy-2-(phosphonomethoxy)propyl Nucleosides Against Herpesviruses and Orthopoxviruses≠

PubMed Central

Valiaeva, Nadejda; Prichard, Mark N.; Buller, R. Mark; Beadle, James R.; Hartline, Caroll B.; Keith, Kathy A.; Schriewer, Jill; Trahan, Julissa; Hostetler, Karl Y.

2009-01-01

Our previous studies showed that esterification of (S)-3-hydroxy-2-(phosphono-methoxy)propyl]adenine (HPMPA) or 1-(S)-[3-hydroxy-2-(phosphonomethoxy)-propyl]cytosine (HPMPC) with alkoxyalkyl groups such as hexadecyloxypropyl (HDP) or octadecyloxyethyl (ODE) resulted in large increases in antiviral activity and oral bioavailability. The HDP- and ODE- esters of HPMPA were shown to be active in cells infected with human immunodeficiency virus, type 1 (HIV-1), while HPMPA itself was virtually inactive. To explore this approach in greater detail, we synthesized four new compounds in this series, the ODE esters of 9-(S)-[3-hydroxy-2-(phosphonomethoxy)-propyl]guanine (HPMPG), 1-(S)-[3-hydroxy-2-(phosphono-methoxy)propyl]thymine (HPMPT), 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-2,6-diaminopurine (HPMPDAP) and 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-2-amino-6-cyclopropylaminopurine. (HPMP-cPrDAP) and evaluated their antiviral activity against herpes simplex virus, type 1 (HSV-1), human cytomegalovirus (HCMV), and vaccinia, cowpox and ectromelia. Against HSV-1, subnanomolar EC50 values were observed with ODE-HPMPA and ODE-HPMPC while ODE-HPMPG had intermediate antiviral activity with an EC50 of 40 nanomolar. In HFF cells infected with HCMV, the lowest EC50 values were observed with ODE-HPMPC, 0.9 nanomolar. ODE -HPMPA was highly active with an EC50 of 3 nanomolar, while ODE-HPMPG and ODE-HPMPDAP were also highly active with EC50s of 22 and 77 nanomolar, respectively. Against vaccinia and cowpox viruses, ODE-HPMPG and ODE-HPMPDAP were the most active and selective compounds with EC50 values of 20 to 60 nanomolar and selectivity index values of 600 to 3,500. ODE-HPMPG was also active against ectromelia virus with an EC50 value of 410 nanomolar and a selectivity index value of 166. ODE-HPMPG and ODE-HPMPDAP are proposed for further preclinical evaluation as possible candidates for treatment of HSV, HCMV or orthopoxvirus diseases. PMID:19800369

Biased ligand quantification in drug discovery: from theory to high throughput screening to identify new biased μ opioid receptor agonists

PubMed Central

Winpenny, David; Clark, Mellissa

2016-01-01

Background and Purpose Biased GPCR ligands are able to engage with their target receptor in a manner that preferentially activates distinct downstream signalling and offers potential for next generation therapeutics. However, accurate quantification of ligand bias in vitro is complex, and current best practice is not amenable for testing large numbers of compound. We have therefore sought to apply ligand bias theory to an industrial scale screening campaign for the identification of new biased μ receptor agonists. Experimental Approach μ receptor assays with appropriate dynamic range were developed for both Gαi‐dependent signalling and β‐arrestin2 recruitment. Δlog(Emax/EC50) analysis was validated as an alternative for the operational model of agonism in calculating pathway bias towards Gαi‐dependent signalling. The analysis was applied to a high throughput screen to characterize the prevalence and nature of pathway bias among a diverse set of compounds with μ receptor agonist activity. Key Results A high throughput screening campaign yielded 440 hits with greater than 10‐fold bias relative to DAMGO. To validate these results, we quantified pathway bias of a subset of hits using the operational model of agonism. The high degree of correlation across these biased hits confirmed that Δlog(Emax/EC50) was a suitable method for identifying genuine biased ligands within a large collection of diverse compounds. Conclusions and Implications This work demonstrates that using Δlog(Emax/EC50), drug discovery can apply the concept of biased ligand quantification on a large scale and accelerate the deliberate discovery of novel therapeutics acting via this complex pharmacology. PMID:26791140

Statistical strategies for averaging EC50 from multiple dose-response experiments.

PubMed

Jiang, Xiaoqi; Kopp-Schneider, Annette

2015-11-01

In most dose-response studies, repeated experiments are conducted to determine the EC50 value for a chemical, requiring averaging EC50 estimates from a series of experiments. Two statistical strategies, the mixed-effect modeling and the meta-analysis approach, can be applied to estimate average behavior of EC50 values over all experiments by considering the variabilities within and among experiments. We investigated these two strategies in two common cases of multiple dose-response experiments in (a) complete and explicit dose-response relationships are observed in all experiments and in (b) only in a subset of experiments. In case (a), the meta-analysis strategy is a simple and robust method to average EC50 estimates. In case (b), all experimental data sets can be first screened using the dose-response screening plot, which allows visualization and comparison of multiple dose-response experimental results. As long as more than three experiments provide information about complete dose-response relationships, the experiments that cover incomplete relationships can be excluded from the meta-analysis strategy of averaging EC50 estimates. If there are only two experiments containing complete dose-response information, the mixed-effects model approach is suggested. We subsequently provided a web application for non-statisticians to implement the proposed meta-analysis strategy of averaging EC50 estimates from multiple dose-response experiments.

Experimental determinations of soil copper toxicity to lettuce (Lactuca sativa) growth in highly different copper spiked and aged soils.

PubMed

Christiansen, Karen S; Borggaard, Ole K; Holm, Peter E; Vijver, Martina G; Hauschild, Michael Z; Peijnenburg, Willie J G M

2015-04-01

Accurate knowledge about factors and conditions determining copper (Cu) toxicity in soil is needed for predicting plant growth in various Cu-contaminated soils. Therefore, effects of Cu on growth (biomass production) of lettuce (Lactuca sativa) were tested on seven selected, very different soils spiked with Cu and aged for 2 months at 35 °C. Cu toxicity was expressed as pEC50(Cu(2+)), i.e., the negative logarithm of the EC50(Cu(2+)) activity to plant growth. The determined pEC50(Cu(2+)) was significantly and positively correlated with both the analytically readily available soil pH and concentration of dissolved organic carbon [DOC] which together could explain 87% of the pEC50(Cu(2+)) variation according to the simple equation: pEC50(Cu(2+)) = 0.98 × pH + 345 × [DOC] - 0.27. Other soil characteristics, including the base cation concentrations (Na(+), K(+), Ca(2+), Mg(2+)), the cation exchange capacity at soil pH (ECEC), and at pH 7 (CEC7), soil organic carbon, clay content, and electric conductivity as well as the distribution coefficient (Kd) calculated as the ratio between total soil Cu and water-extractable Cu did not correlate significantly with pEC50(Cu(2+)). Consequently, Cu toxicity, expressed as the negative log of the Cu(2+) activity, to plant growth increases at increasing pH and DOC, which needs to be considered in future management of plant growth on Cu-contaminated soils. The developed regression equation allows identification of soil types in which the phytotoxicity potential of Cu is highest.

Sensitivity of Ethiopian aquatic macroinvertebrates to the pesticides endosulfan and diazinon, compared to literature data.

PubMed

Teklu, Berhan M; Retta, Negussie; Van den Brink, Paul J

2016-08-01

The aims of the present study were to present a methodology for toxicity tests that can be used when analytical resources to verify the test concentrations are limited, and to evaluate whether the sensitivity of a limited number of Ethiopian species to pesticides differs from literature values for, mainly, temperate species. Acute toxicity tests were performed using three Ethiopian aquatic invertebrate species, one crustacean (Diaphanosoma brachyurum) and two insects (Anopheles pharoensis and Culex pipiens) and using the pesticides endosulfan and diazinon. All species-pesticide combinations were tested in duplicate to estimate the consistency, i.e. the intra-laboratory variation, in test results. Daphnia magna was tested as well to allow the test results to be compared directly with values from the literature. Results indicate that the differences between the EC50s obtained for D. magna in this study and those reported in the literature were less than a factor of 2. This indicates that the methodology used is able to provide credible toxicity values. The results of the duplicated tests showed intra-laboratory variation in EC50 values of up to a factor of 3, with one test showing a difference of a factor of 6 at 48 h. Comparison with available literature results for arthropod species using species sensitivity distributions indicated that the test results obtained in this study fit well in the log-normal distribution of the literature values. We conclude that the methodology of performing multiple tests to check for consistency of test results and performing tests with D. magna for comparison with literature values to check for accuracy is able to provide reliable effect threshold levels and that the tested Ethiopian species did not differ in sensitivity from the arthropod species reported on in the literature.

Fused heterocycles bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 3: optimization of [1,2,4]triazolo[1,5-a]pyrimidine core via structure-based and physicochemical property-driven approaches.

PubMed

Huang, Boshi; Li, Cuicui; Chen, Wenmin; Liu, Tao; Yu, Mingyan; Fu, Lu; Sun, Yueyue; Liu, Huiqing; De Clercq, Erik; Pannecouque, Christophe; Balzarini, Jan; Zhan, Peng; Liu, Xinyong

2015-03-06

In our arduous efforts to develop new potent HIV-1 non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs), novel piperidine-linked [1,2,4]triazolo[1,5-a]pyrimidine derivatives were designed, synthesized and evaluated for their antiviral activities in MT-4 cell cultures. Biological results showed that all of the title compounds displayed moderate to excellent activities against wild-type (wt) HIV-1 strain (IIIB) with EC50 values ranging from 8.1 nM to 2284 nM in a cell-based assay. Among them, the most promising analog 7d possessed an EC50 value of 8.1 nM against wt HIV-1, which was much more potent than the reference drugs DDI, 3 TC, NVP and DLV. Additionally, 7d demonstrated weak activity against the double mutant HIV-1 strain (K103N + Y181C), and was more efficient than NVP in a RT inhibition assay. Besides, some measured and calculated physicochemical properties of 7d, like log P and water solubility, as well as the structure-activity relationships (SARs) analysis have been discussed in detail. Furthermore, the binding mode of the active compound 7d was rationalized by molecular simulation studies. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Effects of fenoterol on beta-adrenoceptor and muscarinic M2 receptor function in bovine tracheal smooth muscle.

PubMed

De Vries, B; Roffel, A F; Kooistra, J M; Meurs, H; Zaagsma, J

2001-05-11

Prolonged (18 h) incubation of isolated bovine tracheal smooth muscle with the beta2-adrenoceptor agonist fenoterol (10 microM) induced desensitization of isoprenaline-induced adenylyl cyclase activity in bovine tracheal smooth muscle membranes, characterized by a 25% decrease in maximal effect (Emax) (P < 0.05), while the sensitivity to the agonist (pEC50) was unchanged. The Emax value of isoprenaline-induced smooth muscle relaxation of submaximal methacholine-induced contractile tones was similarly reduced by about 25% (P < 0.001), while the pEC50 value was diminished by 1.0 log unit (P < 0.001). As determined by 30 microM gallamine-induced muscarinic M2 receptor antagonism and pertussis toxin-induced inactivation of G(i alpha), muscarinic M2 receptor-mediated functional antagonism did not play a role in isoprenaline-induced relaxation of bovine tracheal smooth muscle contracted by methacholine, both in control and in 18-h fenoterol-treated tissue. In line with these observations, we found no enhanced muscarinic M2 receptor-mediated inhibition of 1 microM forskolin-stimulated adenylyl cyclase activity after 18-h fenoterol treatment. These data indicate that 18-h fenoterol treatment of bovine tracheal smooth muscle induces beta2-adrenoceptor desensitization and reduced functional antagonism of methacholine-induced contraction by beta-adrenoceptor agonists, without a change of muscarinic M2 receptor function.

Assessment of sublethal endpoints after chronic exposure of the nematode Caenorhabditis elegans to palladium, platinum and rhodium.

PubMed

Schertzinger, Gerhard; Zimmermann, Sonja; Grabner, Daniel; Sures, Bernd

2017-11-01

The aim of this study was to investigate chronic effects of the platinum-group elements (PGE) palladium (Pd), platinum (Pt) and rhodium (Rh) on the nematode Caenorhabditis elegans. Aquatic toxicity testing was carried out according to ISO 10872 by determining 96 h EC 50 values for sublethal endpoints, including growth, fertility and reproduction. Single PGE standard solutions were used as metal source. Based on the EC 50 values for Pt, reproduction (96 h EC 50  = 497 μg/L) was the most sensitive endpoint followed by fertility (96 h EC 50  = 726 μg/L) and growth (96 h EC 50  = 808 μg/L). For Pd, no precise EC 50 values could be calculated due to bell-shaped concentration response curves, but the 96 h EC 50 for reproduction ranged between 10 and 100 μg/L. Pd and Pt had effects on all endpoints. With raising element concentrations reproduction was inhibited first. At a certain concentration, fertility was also affected, which in turn had an additional effect on reproduction. Growth inhibition can also lead to a loss of fertility if the worms do not reach an appropriate body size to become fertile. Rhodium showed no inhibition of any endpoint between concentrations of 100 to 10,000 μg Rh/L. The results of this study allow the following order of PGE with respect to decreasing toxicity to C. elegans: Pd > Pt » Rh. Copyright © 2017 Elsevier Ltd. All rights reserved.

Preformulation studies of EFdA, a novel nucleoside reverse transcriptase inhibitor for HIV prevention

PubMed Central

Zhang, Wei; Parniak, Michael A.; Mitsuya, Hiroaki; Sarafianos, Stefan G.; Graebing, Phillip W.; Rohan, Lisa C.

2014-01-01

4′-Ethynyl-2-fluoro-2′-deoxyadenosine (EFdA) is a novel nucleoside analog of great interest because of its superior activity against wild-type and multidrug-resistant HIV-1 strains, and favorable safety profiles in vitro and in vivo. The aim of this work was to provide preformulation information of EFdA important for delivery system development. A simple, accurate and specific reverse-phase high performance liquid chromatographic (RP-HPLC) method with UV detection was developed for quantification of EFdA. In addition, physicochemical characterizations including pH solubility profile, octanol/water partition coefficient (Log Po/w), DSC analysis, field emission scanning electron microscopy, and stability studies under various conditions were conducted. EFdA existed in planar or flake shape, with a melting point of ~130 °C, and had a pH dependent solubility. The log Po/w value of EFdA was −1.19. The compound was stable upon exposure to pH levels from 3 to 9 and showed good stability at elevated temperature (65 °C). In vitro cytotoxicity assessments were performed in two different epithelial cell lines. In cell-based studies, the EFdA selectivity index (50% cytotoxic concentration [CC50] values/50% effective concentration [EC50]) was found to be greater than 1 × 103. Permeability studies using cell- and tissue-based models showed that EFdA had an apparent permeability coefficient (Papp) <1 × 10−6cm/s and that the paracelluar pathway was the dominant transport route for EFdA. Overall, EFdA possesses favorable characteristics for further formulation development. PMID:23841536

Preformulation studies of EFdA, a novel nucleoside reverse transcriptase inhibitor for HIV prevention.

PubMed

Zhang, Wei; Parniak, Michael A; Mitsuya, Hiroaki; Sarafianos, Stefan G; Graebing, Phillip W; Rohan, Lisa C

2014-08-01

4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) is a novel nucleoside analog of great interest because of its superior activity against wild-type and multidrug-resistant HIV-1 strains, and favorable safety profiles in vitro and in vivo. The aim of this work was to provide preformulation information of EFdA important for delivery system development. A simple, accurate and specific reverse-phase high performance liquid chromatographic (RP-HPLC) method with UV detection was developed for quantification of EFdA. In addition, physicochemical characterizations including pH solubility profile, octanol/water partition coefficient (Log Po/w), DSC analysis, field emission scanning electron microscopy, and stability studies under various conditions were conducted. EFdA existed in planar or flake shape, with a melting point of ∼130 °C, and had a pH dependent solubility. The log Po/w value of EFdA was -1.19. The compound was stable upon exposure to pH levels from 3 to 9 and showed good stability at elevated temperature (65 °C). In vitro cytotoxicity assessments were performed in two different epithelial cell lines. In cell-based studies, the EFdA selectivity index (50% cytotoxic concentration [CC50] values/50% effective concentration [EC50]) was found to be greater than 1 × 10(3). Permeability studies using cell- and tissue-based models showed that EFdA had an apparent permeability coefficient (Papp) <1 × 10(-6)cm/s and that the paracelluar pathway was the dominant transport route for EFdA. Overall, EFdA possesses favorable characteristics for further formulation development.

Synthesis and antifungal evaluation of PCA amide analogues.

PubMed

Qin, Chuan; Yu, Di-Ya; Zhou, Xu-Dong; Zhang, Min; Wu, Qing-Lai; Li, Jun-Kai

2018-04-18

To improve the physical and chemical properties of phenazine-1-carboxylic acid (PCA) and find higher antifungal compounds, a series of PCA amide analogues were designed and synthesized and their structures were confirmed by 1 H NMR, HRMS, and X-ray. Most compounds showed some antifungal activities in vitro. Particularly, compound 3d exhibited inhibition effect against Pyriculariaoryzac Cavgra with EC 50 value of 28.7 μM and compound 3q exhibited effect against Rhizoctonia solani with EC 50 value of 24.5 μM, more potently active than that of the positive control PCA with its EC 50 values of 37.3 μM (Pyriculariaoryzac Cavgra) and 33.2 μM (Rhizoctonia solani), respectively.

Assessing single and joint toxicity of three phenylurea herbicides using Lemna minor and Vibrio fischeri bioassays.

PubMed

Gatidou, Georgia; Stasinakis, Athanasios S; Iatrou, Evangelia I

2015-01-01

Single and joint toxicity of three substituted urea herbicides, namely monolinuron [3-(4-chlorophenyl)-1-methoxy-1-methylurea], linuron [3-(3,4-dichlorophenyl)-1-methoxy-1-methylurea] and diuron [1-(3,4 dichlorophenyl)-3,3 dimethyl urea], were studied. The duckweed Lemna minor and the luminescent bacterium Vibrio fischeri were used for the toxicity assessment and they were exposed to various concentrations of the herbicides, individually and in binary mixtures. The exposure time was 7d for the duckweed and 30 min for the bacterium. Estimation of EC50 values was performed by frond counting and reduction in light output for Lemna minor and Vibrio fischeri, respectively. Lemna minor was found to be much more sensitive than Vibrio fischeri to target compounds. The toxicity of the three herbicides applied solely was estimated to be in decreasing order: diuron (EC50=28.3 μg L(-1))≈linuron (EC50=30.5 μg L(-1))>monolinuron (EC50=300 μg L(-1)) for the duckweed and linuron (EC50=8.2 mg L(-1))>diuron (EC50=9.2 mg L(-1))>monolinuron (EC50=11.2 mg L(-1)) for the bacterium. Based on the environmental concentrations reported in the literature and EC50 values obtained from Lemna minor experiments, Risk Quotients (RQ) much higher than 1 were calculated for diuron and linuron. In Lemna minor experiments, combination of target compounds resulted to additive effects due to their same mode of phenylurea action on photosynthetic organisms. Regarding Vibrio fischeri, synergistic, additive and antagonistic effects were observed, which varied according to the concentrations of target compounds. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of whole-body and local heating on cutaneous vasoconstrictor responses in humans

NASA Technical Reports Server (NTRS)

Wilson, Thad E.; Cui, Jian; Crandall, Craig G.

2002-01-01

Animal studies suggest that alpha-adrenergic-mediated vasoconstriction is compromised during whole-body heating. The purpose of this study was to identify whether whole-body heating and/or local surface heating reduce cutaneous alpha-adrenergic vasoconstrictor responsiveness in human skin. Protocol I: Six subjects were exposed to neutral skin temperature (i.e., 34 degrees C), whole-body heating, and local heating of forearm skin to increase skin blood flow to the same relative magnitude as that observed during whole-body heating. Protocol II: In eight subjects forearm skin was locally heated to 34, 37, 40, and 42 degrees C. During both protocols, alpha-adrenergic vasoconstrictor responsiveness was assessed by local delivery of norepinephrine (NE) via intradermal microdialysis. Skin blood flow was continuously monitored over each microdialysis membrane via laser-Doppler flowmetry. In protocol I, whole-body and local heating caused similar increases in cutaneous vascular conductance (CVC). The EC50 (log NE dose) of the dose-response curves for both whole body (-4.2 +/- 0.1 M) and local heating (-4.7 +/- 0.4 M) were significantly greater (i.e., high dose required to cause 50% reduction in CVC) relative to neutral skin temperature (- 5.6 +/- 0.0 M; P<0.05 for both). In both local and whole-body heated conditions CVC did not return to pre-heating values even at the highest dose of NE. In protocol II, calculated EC50 for 34, 37, 40, and 42 degrees C local heating was - 5.5 +/- 0.4, -4.6 +/- 0.3, -4.5 +/- 0.3, - 4.2 +/- 0.4 M, respectively. Statistical analyses revealed that the EC50 for 37,40 and 42 degrees C were significantly greater than the EC50 for 34 degrees C. These results indicate that even during administration of high concentrations of NE, alpha-adrenergic vasoconstriction does not fully compensate for local heating and whole-body heating induced vasodilatation in young, healthy subjects. Moreover, these data suggest that elevated local temperatures, above 37 degrees C, and whole-body heating similarly attenuate cutaneous alpha-adrenergic vasoconstriction responsiveness.

Nematicidal activity of acetophenones and chalcones against Meloidogyne incognita and structure-activity considerations.

PubMed

Caboni, Pierluigi; Aissani, Nadhem; Demurtas, Monica; Ntalli, Nikoletta; Onnis, Valentina

2016-01-01

With the ultimate goal of identifying new compounds active against root-knot nematodes, a set of 14 substituted chalcones were synthesised, starting from acetophenones. These chalcones and various acetophenones were tested in vitro against Meloidogyne incognita. The most potent acetophenones were 4-nitroacetophenone and 4-iodoacetophenone, with EC(50/24 h) values of 12 ± 5 and 15 ± 4 mg L(-1) respectively, somewhat weaker than that of the chemical control fosthiazate in our previous experiments (EC(50/24 h) 0.4 ± 0.3 mg L(-1)). When we converted the acetophenones to chalcones, the nematicidal activity differed, based on their substitution pattern. The condensation of 4-nitroacetophenone with 2,4,6-trihydroxybenzaldehyde to give the corresponding chalcone (E)-1-(4-nitrophenyl)-3-(2,4,6-trihydroxyphenyl)prop-2-en-1-one led to a slight reduction in activity (EC(50/24 h) value 25 ± 17 mg L(-1)). Moreover, (E)-3-(2-hydroxy-5-iodophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one showed better activity (EC(50/24) h value 26 ± 15 mg L(-1)) than 4-methoxyacetophenone (EC(50/24 h) value 43 ± 10 mg L(-1)). Acetophenones and chalcones may represent good leads in the discovery of new nematicidal compounds and may have potential use in crop management as active ingredients. © 2015 Society of Chemical Industry.

Radical scavenging activity of protein from tentacles of jellyfish Rhopilema esculentum.

PubMed

Yu, Huahua; Liu, Xiguang; Xing, Ronge; Liu, Song; Li, Cuiping; Li, Pengcheng

2005-05-16

In this study, radical scavenging activity of protein from tentacles of jellyfish Rhopilema esculentum (R. esculentum) was assayed including superoxide anion radical and hydroxyl radical scavenging. The protein samples showed strong scavenging activity on superoxide anion radical and values EC50 of full protein (FP), first fraction (FF), second fraction (SF), and 30% (NH4)2 SO4 precipitate (Fr-1) were 2.65, 7.28, 1.10, and 22.51 microg/mL, respectively, while values EC50 of BHA, BHT, and alpha-tocopherol were 31, 61, and 88 microg/mL, respectively. Also, the protein samples had strong scavenging effect on hydroxyl radical and the values EC50 of FP, FF, SF, Fr-1, and Fr-2 were 48.91, 27.72, 1.82, 16.36, and 160.93 microg/mL, but values EC50 of Vc and mannitol were 1907 and 4536 microg/mL, respectively. Of the five protein samples, SF had the strongest radical scavenging activity and may have a use as a possible supplement in the food and pharmaceutical industries. The radical scavenging activity was stable at high temperature so that R. esculentum may be used as a kind of natural functional food.

Evaluation of a three-dimensional human dermal model as a predictor of shampoo ocular irritation.

PubMed

Decker, D; Harper, R

1994-04-01

A three-dimensional human tissue model (Skin(2) ZK1100) was used to evaluate 43 adult and baby shampoos. The ZK1100 model consists of metabolically active proliferating human fibroblasts isolated from the dermis of neonatal foreskins and seeded onto a nylon mesh. The fibroblasts multiply and produce matrix proteins to form a living tissue. MTT reduction (mitochondrial function) was used as the cytotoxicity endpoint. The primary components of the adult shampoos are alkyl sulfate surfactants, while the baby shampoos contain ethoxylated alkyl sulfates and amphoteric surfactants. All shampoos were diluted to five concentrations (100, 300, 700, 1000 and 3000 mug/ml) in aqueous cell culture media and the tissue exposed for 24 hr. An EC(50) value for each test was generated from a dose-response curve. All samples were tested in two or more separate experiments, and the EC(50) values were averaged and plotted versus their respective 24-hr unwashed Draize eye irritation values (r(2) = 0.81). The adult shampoos had Draize values in the moderate irritation category and EC(50) values ranging from 220 to 1051 mug/ml, while the baby shampoos had Draize values in the minimal irritation category and EC(50) values ranging from 820 to 2285 mug/ml. These results indicate that the three-dimensional human tissue model can be useful in predicting the Draize ocular irritation category for shampoos.

Sensitivity limits and EC50 values of the Vibrio fischeri test for organic micropollutants in natural and spiked extracts from sediments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salizzato, M.; Bertato, V.; Pavoni, B.

1998-04-01

Chemical analyses and bioassays were used in conjunction to assess the quality of sediments of the Venice lagoon. Organic micropollutants (polycyclic aromatic hydrocarbons [PAHs] polychlorinated biphenyls [PCBs], and chlorinated pesticides) were extracted from sediment samples and analyzed by gas chromatography after fractionation into classes of compounds. The Vibrio fischeri test was used to assess the acute toxicity of sediment extracts. The test was applied to organic extracts before cleanup and to extracts purified from sulfur and fractionated into single classes of compounds. Extracts before purification were much more toxic than single fractions. In particular, sulfur was toxic to V. fischeri.more » For PAHs and PCBs the 50% effective concentration (EC50) and EC20 values were determined using natural and spiked extracts. Sensitivity limits of the method for these compounds were also estimated as was in EC50 value of elemental sulfur dissolved in ethanol. A mathematical model was used to fit the concentration-response data to a sigmoid curve.« less

Interaction of carvacrol with the Ascaris suum nicotinic acetylcholine receptors and gamma-aminobutyric acid receptors, potential mechanism of antinematodal action

PubMed Central

Marjanović, Djordje S.; Trailović, Jelena Nedeljković; Robertson, Alan P.; Martin, Richard J.

2015-01-01

Essential plant oils (or their active principles) are safe to use and a potentially attractive alternative to current antiparasitic drugs. In the present study, we tested the effects of carvacrol on the isolated tissues of Ascaris suum and investigated potential interactions with other antiparasitic drugs. We used somatic muscle flaps for contraction assays, as well as for electrophysiological investigations. Carvacrol 300 μM highly significantly inhibited contractions caused by 1, 3, 10, 30, and 100 μM of ACh (p=0.0023, p=0.0002, p=0.0002, p<0.0001, and p<0.0001). The control EC50 for acetylcholine was 8.87 μM (log EC50=0.95±0.26), while Rmax was 2.53±0.24 g. The EC50 of acetylcholine in the presence of 300 μM of carvacrol was 27.71 μM (log EC50=1.44±0.28) and the Rmax decreased to 1.63±0.32 g. Furthermore, carvacrol highly significant potentiates inhibitory effect of GABA and piperazine on the contractions induced by ACh. However, carvacrol (100 and 300 μM), did not produce any changes in the membrane potential or conductance of the A. suum muscle cell. While, 300 μM of carvacrol showed a significant inhibitory effect on ACh-induced depolarization response. The mean control depolarization was 13.58±0.66 mV and decreased in presence of carvacrol to 4.50±1.02 mV (p<0.0001). Mean control Δg was 0.168±0.017 μS, while in the presence of 300 μM of carvacrol, Δg significantly decreased to 0.060±0.018 ΔS (p=0.0017). The inhibitory effect on contractions may be the explanation of the antinematodal potential of carvacrol. Moreover, inhibition of depolarizations caused by ACh and reduction of conductance changes directly points to an interaction with the nAChR in A. suum. PMID:25944741

Screening for unicellular algae as possible bioassay organisms for monitoring marine water samples.

PubMed

Millán de Kuhn, Rosmary; Streb, Christine; Breiter, Roman; Richter, Peter; Neesse, Thomas; Häder, Donat-Peter

2006-08-01

ECOTOX is an automatic early warning system to monitor potential pollution of freshwater, municipal or industrial waste waters or aquatic ecosystems. It is based on a real time image analysis of the motility and orientation parameters of the unicellular, photosynthetic flagellate Euglena gracilis. In order to widen the use of the device to marine habitats and saline waters nine marine flagellates were evaluated as putative bioassay organisms, viz. Dunaliella salina, Dunaliella viridis, Dunaliella bardawil, Prorocentrum minimum Kattegat, P. minimum Lissabon, Tetraselmis suecica, Heterocapsa triquetra, Gyrodinium dorsum and Cryptomonas maculata. Because of their slow growth the last three strains were excluded from further evaluation. Selection criteria were ease of culture, density of cell suspension, stability of motility and gravitactic orientation. The sensitivity toward toxins was tested using copper(II) ions. The instrument allows the user to automatically determine effect-concentration (EC) curves from which the EC(50) values can be calculated. For the interpretation of the EC curves a sigmoid logistic model was proposed which proved to be satisfactory for all tested strains. The inhibition of the motility was considered as the most appropriate movement parameter as an endpoint. The Dunaliella species had the lowest sensitivity to copper with EC(50) values of 220, 198 and 176 mg/L for D. salina, D. bardawil and D. viridis, respectively, followed by T. suecica with an EC(50) value of 40 mg/L. The Prorocentrum species were found to be the most sensitive with an EC(50) value of 13.5 mg/L for P. minimum Lissabon and 7.5 mg/L for P. minimum Kattegat.

Evaluating the Teratogenicity of Ritodrine and Nifedipine using a Frog Embryo Teratogenesis assay (FETAX).

PubMed

Boğa Pekmezekmek, Ayper; Binokay, Uğur Seçil; Seçilmiş, Mehmet Ata; Kumcu, Eda; Şimşek, Erhan; Akillioğlu, Kübra; Sertdemir, Yaşar; Özaykan, Besim

2015-01-01

The Frog Embryo Teratogenesis Assay-Xenopus (FETAX) was used to assess the teratogenic potential of two tocolytics. Embryos of the South African clawed frog, Xenopus laevis, were exposed to ritodrine or nifedipine. Exposure media were changed and monitored at 24-hour intervals. The 96-hour LC50 (Lethal concentration), the 96-hour EC50 (Malformation), and the No Observable Adverse Effect Concentrations (NOAEC) and the Lowest Observable Adverse Effect Concentration (LOAEC) for mortality, malformation and length were determined for each drug. Nifedipine was determined to be the more toxic and teratogenic than ritodrine, with a LC50 of 0.606 µg/L, an EC50 of 0.006 µg/L, and a teratogenicity Index (TI) value (LC50/EC50) of 101. On the other hand, the LC50 of ritodrine was 28.571 mg/L. In addition; the LC50, EC50 and TI values for nifedipine in the 5 mg/L ritodrine + nifedipine combination group were determined as 1.050 µg/L, 0.868 µg/L and 1.5 respectively. For ritodrine, the NOAEC and LOAEC values were determined as 2 mg/L and 4 mg/L, respectively. For the nifedipine and the ritodrine + nifedipine groups; while the LOAEC values of these groups were 0.0001 µg/L and 0.1 µg/L, respectively. NOAEC value couldn't be determined. Our results demonstrated that nifedipine administration was associated with higher levels of teratogenic and toxic effects. However, the ritodrine + nifedipine combination form reduced the toxic and teratogenic effects of nifedipine on Xenopus embryos. Further studies should be conducted in order to investigate the optimal combination concentrations of these substances for the treatment of preterm labor.

40 CFR 799.4360 - Tributyl phosphate.

Code of Federal Regulations, 2010 CFR

2010-07-01

... or aquatic invertebrate EC50 or LC50 is ≤ 100 mg/L and either the rainbow trout or gammarid 24-hour... value is ≤ 1 mg/L; or any fish or aquatic invertebrate EC50 or LC50 is ≤ 100 mg/L and either the rainbow... invertebrate bioassay—(i) Required testing. (A) A benthic sediment invertebrate bioassay shall be conducted on...

Syntheses of cytotoxic novel arctigenin derivatives bearing halogen and alkyl groups on aromatic rings.

PubMed

Yamauchi, Satoshi; Wukirsari, Tuti; Ochi, Yoshiaki; Nishiwaki, Hisashi; Nishi, Kosuke; Sugahara, Takuya; Akiyama, Koichi; Kishida, Taro

2017-09-01

The new lignano-9,9'-lactones (α,β-dibenzyl-γ-butyrolactone lignans), which showed the higher cytotoxicity than arctigenin, were synthesized. The well-known cytotoxic arctigenin showed activity against HL-60 cells (EC 50 =12μM), however, it was inactive against HeLa cells (EC 50 >100μM). The synthesized (3,4-dichloro, 2'-butoxy)-derivative 55 and (3,4-dichloro, 4'-butyl)-derivative 66 bearing the lignano-9,9'-lactone structures showed the EC 50 values of 10μM and 9.4μM against HL-60 cells, respectively. Against HeLa cells, the EC 50 value of the derivative 66 was 27μM. By comparing the activities with the corresponding 9,9'-epoxy structure (tetrahydrofuran compounds), the importance of the lactone structure of 55 and 66 for the higher activities was shown. The substituents on the aromatic ring of the lignano-9,9'-lactones affected the cytotoxicity level, observing more than 10-fold difference. Copyright © 2017. Published by Elsevier Ltd.

Near-equipartition Jets with Log-parabola Electron Energy Distribution and the Blazar Spectral-index Diagrams

NASA Astrophysics Data System (ADS)

Dermer, Charles D.; Yan, Dahai; Zhang, Li; Finke, Justin D.; Lott, Benoit

2015-08-01

Fermi-LAT analyses show that the γ-ray photon spectral indices {{{Γ }}}γ of a large sample of blazars correlate with the ν {F}ν peak synchrotron frequency {ν }s according to the relation {{{Γ }}}γ =d-k{log} {ν }s. The same function, with different constants d and k, also describes the relationship between {{{Γ }}}γ and peak Compton frequency {ν }{{C}}. This behavior is derived analytically using an equipartition blazar model with a log-parabola description of the electron energy distribution (EED). In the Thomson regime, k={k}{EC}=3b/4 for external Compton (EC) processes and k={k}{SSC}=9b/16 for synchrotron self-Compton (SSC) processes, where b is the log-parabola width parameter of the EED. The BL Lac object Mrk 501 is fit with a synchrotron/SSC model given by the log-parabola EED, and is best fit away from equipartition. Corrections are made to the spectral-index diagrams for a low-energy power-law EED and departures from equipartition, as constrained by absolute jet power. Analytic expressions are compared with numerical values derived from self-Compton and EC scattered γ-ray spectra from Lyα broad-line region and IR target photons. The {{{Γ }}}γ versus {ν }s behavior in the model depends strongly on b, with progressively and predictably weaker dependences on γ-ray detection range, variability time, and isotropic γ-ray luminosity. Implications for blazar unification and blazars as ultra-high energy cosmic-ray sources are discussed. Arguments by Ghisellini et al. that the jet power exceeds the accretion luminosity depend on the doubtful assumption that we are viewing at the Doppler angle.

Chronic sensitivity of white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss) to cadmium, copper, lead, or zinc in laboratory water-only exposures

USGS Publications Warehouse

Wang, Ning; Ingersoll, Christopher G.; Dorman, Rebecca A.; Brumbaugh, William G.; Mebane, Christopher A.; Kunz, James L.; Hardesty, Douglas K.

2014-01-01

Chronic toxicity of cadmium, copper, lead, or zinc to white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss) was evaluated in water-only exposures started with newly hatched larvae or approximately 1-mo-old juveniles. The 20% effect concentration (EC20) for cadmium from the sturgeon tests was higher than the EC20 from the trout tests, whereas the EC20 for copper, lead, or zinc for the sturgeon were lower than those EC20s for the trout. When the EC20s from the present study were included in compiled toxicity databases for all freshwater species, species mean chronic value for white sturgeon was in a relatively low percentile of the species sensitivity distribution for copper (9th percentile) and in the middle percentile for cadmium (55th percentile), zinc (40th percentile), or lead (50th percentile). However, the species mean chronic value for rainbow trout was in a high percentile for copper, lead, and zinc (∼68th–82nd percentile), but in a low percentile for cadmium (23rd percentile). The trout EC20s for each of the 4 metals and the sturgeon EC20s for cadmium or lead were above US Environmental Protection Agency chronic ambient water quality criteria (AWQC) or Washington State chronic water quality standards (WQS), whereas the sturgeon EC20s for copper or zinc were approximately equal to or below the chronic AWQC and WQS. In addition, acute 50% effect concentrations (EC50s) for copper obtained in the first 4 d of the chronic sturgeon test were below the final acute value used to derive acute AWQC and below acute WQS for copper.

Effects of ozone on the cholinergic secretory responsiveness of ferret tracheal glands

DOE Office of Scientific and Technical Information (OSTI.GOV)

McBride, R.K.; Oberdoerster, G.; Marin, M.G.

1991-06-01

Oxidant air pollutants exacerbate several pulmonary diseases. Inhalation of ozone has been shown to induce airway smooth muscle hyperresponsiveness. Oxidant injury could also affect airway secretory mechanisms. The authors postulated that oxidant exposure would alter the glycoconjugate secretory function of airway submucosal glands. To test this hypothesis they examined the effects of in vivo ozone exposure on the in vitro secretory responsiveness of ferret tracheal glands. Ferrets were exposed to 1 ppm ozone, 24 hr/day for 3 or 7 days. Following exposure, glandular explants, denuded of surface epithelial cells, were prepared and incubated in medium containing 3H-glucosamine for 18 hr.more » Basal secretion of labeled glycoconjugates was significantly increased 31% following 3 days of ozone exposure (P less than or equal to 0.05) and remained elevated 11% after 7 days of exposure compared to the air-exposed group. After 3 or 7 days of exposure to ozone, tracheal gland responsiveness to carbachol was increased as indicated by significantly lower EC50 values (log molar concentration) of -6.43 {plus minus} 0.04 (n = 6) and -6.50 {plus minus} 0.11 (n = 5), respectively; compared to -6.20 {plus minus} 0.08 (n = 6) for the air-exposed group. There was no difference in carbachol EC50 values for air and 7-day ozone-exposed animals treated with dexamethasone. Dexamethasone did not attenuate the ozone-induced increase in basal secretion. Tracheal gland responsiveness to {alpha}- or {beta}-adrenergic agonists was not changed by oxidant exposure. These experiments suggest that oxidant injury not only increases basal secretion of respiratory glycoconjugates but also increases tracheal gland sensitivity to a cholinergic agonist.« less

Chronic alcoholism increases the induction dose of propofol.

PubMed

Liang, C; Chen, J; Gu, W; Wang, H; Xue, Z

2011-10-01

The present study was designed to investigate the possible effect of chronic alcohol intake on propofol and remifentanil requirements, which was determined by quantifying the 50% (EC(50) ) and 95% (EC(95) ) effective effect-site concentrations for propofol and remifentanil at loss of consciousness (LOC) and after a painful stimulus. Thirty male patients (alcoholic group; n = 30) with chronic alcoholism and 30 patients (control group; n = 30) with a history of small alcohol intake were anaesthetized with propofol and remifentanil by target-controlled infusion. The predicted drug concentrations and Bispectral Index (BIS) values were recorded at LOC and after no response to painful stimuli. The EC(50) and EC(95) of propofol at LOC in alcoholic group were 3.15 [95% confidence interval (CI), 2.77-3.37] and 4.05 (95% CI, 3.18-5.26) μg/ml, respectively, and those of the control group were 2.21 (95% CI, 1.92-2.86) and 3.04 (95% CI, 2.45-4.64) μg/ml, respectively. The EC(50) and EC(95) of remifentanil measured after no response to painful stimuli in the alcoholic group were 3.02 (95% CI, 2.70-3.38) and 4.98 (95% CI, 4.56-5.89) ng/ml, respectively, and those of the control group were 2.95 (95% CI, 2.68-3.33) and 4.86 (95% CI, 4.55-5.92) ng/ml, respectively. The EC(50) and EC(95) values of propofol at LOC in the control group were significantly lower than that of the alcoholic group. These findings suggest that the induction dose requirements of propofol are increased in alcoholic patients anaesthetized with propofol and remifentanil administered by target controlled infusion. 2011 The Authors Acta Anaesthesiologica Scandinavica, 2011 The Acta Anaesthesiologica Scandinavica Foundation.

Is the tier-1 effect assessment for herbicides protective for aquatic algae and vascular plant communities?

PubMed

van Wijngaarden, René P A; Arts, Gertie H P

2018-01-01

In the aquatic tier-1 effect assessment for plant protection products with an herbicidal mode of action in Europe, it is usually algae and/or vascular plants that determine the environmental risks. This tier includes tests with at least 2 algae and 1 macrophyte (Lemna). Although such tests are considered to be of a chronic nature (based on the duration of the test in relation to the life cycle of the organism), the measurement endpoints derived from the laboratory tests with plants (including algae) and used in the first-tier effect assessment for herbicides are acute effect concentrations affecting 50% of the test organisms (EC50 values) and not no-observed-effect concentrations (NOECs) or effect concentrations affecting 10% of the test organisms (EC10) values. Other European legislative frameworks (e.g., the Water Framework Directive) use EC10 values. The present study contributes to a validation of the tiered herbicide risk assessment approach by comparing the standard first-tier effect assessment with results of microcosm and mesocosm studies. We evaluated EC50 and EC10 values for standard test algae and macrophytes based on either the growth rate endpoint (E r C50) or the lowest available endpoint for growth rate or biomass/yield (E r /E y C50). These values were compared with the regulatory acceptable concentrations for the threshold option as derived from microcosm and mesocosm studies. For these studies, protection is maintained if growth rate is taken as the regulatory endpoint instead of the lowest value of either growth rate or biomass/yield in conjunction with the standard assessment factor of 10. Based on a limited data set of 14 herbicides, we did not identify a need to change the current practice. Environ Toxicol Chem 2018;37:175-183. © 2017 SETAC. © 2017 SETAC.

Thiol reactivity and its impact on the ciliate toxicity of α,β-unsaturated aldehydes, ketones, and esters.

PubMed

Böhme, Alexander; Thaens, Diana; Schramm, Franziska; Paschke, Albrecht; Schüürmann, Gerrit

2010-12-20

A recently introduced chemoassay has been used to determine second-order rate constants of the electrophile-nucleophile reaction of 15 α,β-unsaturated aldehydes with glutathione. The respective kGSH values vary for more than 3 orders of magnitude, and are within the range determined previously for 31 α,β-unsaturated ketones and esters. Structure-reactivity analyses yield distinct relationships between kGSH and structural features of the compounds. Moreover, increasing kGSH increases the aldehyde toxicity toward ciliates in terms of 48 h-EC50 values (effective concentration yielding 50% growth inhibition of Tetrahymena pyriformis within 48 h). A respective log-log regression equation including both kGSH and the octanol/water partition coefficient, Kow, yields a squared correlation coefficient of 0.96. Comparative analysis with corresponding data for 15 ketones and 16 esters reveals systematic differences between the three compound classes with regard to the individual contributions of hydrophobicity and electrophilic reactivity to aquatic toxicity. The former is particularly pronounced for aldehydes, while the ester toxicity is largely governed by reactivity, with ketones showing an intermediate pattern that is more similar to the one of esters than of aldehydes. It follows that within the Michael acceptor domain of α,β-unsaturated carbonyls, a distinction between aldehydes and nonaldehydic derivatives appears necessary when employing electrophilic reactivity as a component for the quantitative prediction of their reactive toxicity toward aquatic organisms.

Screening of plant extracts for anthelmintic activity against Dactylogyrus intermedius (Monogenea) in goldfish (Carassius auratus).

PubMed

Huang, Ai-Guo; Yi, Yang-Lei; Ling, Fei; Lu, Lin; Zhang, Qi-Zhong; Wang, Gao-Xue

2013-12-01

With the aim of finding natural anthelmintic agents against Dactylogyrus intermedius (Monogenea) in goldfish (Carassius auratus), 26 plants were screened for antiparasitic properties using in vivo anthelmintic efficacy assay. The results showed that Caesalpinia sappan, Lysima chiachristinae, Cuscuta chinensis, Artemisia argyi, and Eupatorium fortunei were found to have 100% anthelmintic efficacy at 125, 150, 225, 300, and 500 mg L(-1) after 48 h of exposure. Crude extract of the five plants were further partitioned with petroleum ether, chloroform, ethyl acetate, methanol, and water to obtain anthelmintically active fractions with various polarity. Among these fractions tested, the ethyl acetate extract of L. chiachristinae was found to be the most effective with a 50% effective concentration (EC50) value of 5.1 mg/L after 48 h of exposure. This was followed by ethyl acetate extract of C. chinensis (48 h-EC50 = 8.5 mg L(-1)), chloroform extracts of C. sappan (48 h-EC50 = 15.6 mg L(-1)), methanol extract of C. chinensis (48 h-EC50 = 15.9 mg L(-1)), and chloroform and petroleum ether extract of L. chiachristinae (EC50 values of 17.2 and 21.1 mg/L, respectively), suggesting that these plants, as well as the active fractions, provide potential sources of botanic drugs for the control of D. intermedius in aquaculture.

Pharmacokinetic-pharmacodynamic analysis of mnesic effects of lorazepam in healthy volunteers.

PubMed

Blin, O; Jacquet, A; Callamand, S; Jouve, E; Habib, M; Gayraud, D; Durand, A; Bruguerolle, B; Pisano, P

1999-10-01

To describe the pharmacokinetic-pharmacodynamic modelling of the psychomotor and mnesic effects of a single 2 mg oral dose of lorazepam in healthy volunteers. This was a randomized double-blind, placebo-controlled two-way cross-over study. The effect of lorazepam was examined with the following tasks: choice reaction time, immediate and delayed cued recall of paired words and immediate and delayed free recall and recognition of pictures. The mean calculated EC50 values derived from the PK/PD modelling of the different tests ranged from 12.2 to 15.3 ng ml-1. On the basis of the statistical comparison of the EC50 values, the delayed recall trials seemed to be more impaired than the immediate recall trials; similar observations were made concerning the recognition vs recall tasks. The parameter values derived from PK/PD modelling, and especially the EC50 values, may provide sensitive indices that can be used, rather than the raw data derived from pharmacodynamic measurements, to compare CNS effects of benzodiazepines.

Microbial toxicity of methyl tert-butyl ether (MTBE) determined with fluorescent and luminescent bioassays.

PubMed

Roslev, Peter; Lentz, Trine; Hesselsoe, Martin

2015-02-01

The inhibitory effects of the fuel additive methyl tert-butyl ether (MTBE) and potential degradation products tert-butanol (TBA) and formaldehyde was examined using mixed microbial biomass, and six strains of bioluminescent bacteria and yeast. The purpose was to assess microbial toxicity with quantitative bioluminescent and fluorescent endpoints, and to identify sensitive proxies suitable for monitoring MTBE contamination. Bioluminescent Aliivibrio fischeri DSM 7151 (formerly Vibrio fischeri) appeared highly sensitive to MTBE exposure, and was a superior test organisms compared to lux-tagged Escherichia coli DH5α, Pseudomonas fluorescens DF57-40E7 and Saccharomyces cerevisiae BLYR. EC10 and EC50 for acute MTBE toxicity in A. fischeri were 1.1 and 10.9 mg L(-1), respectively. Long term (24h) MTBE exposure resulted in EC10 values of 0.01 mg L(-1). TBA was significantly less toxic with EC10 and EC50 for acute and chronic toxicity >1000 mg L(-1). Inhibition of bioluminescence was generally a more sensitive endpoint for MTBE toxicity than measuring intracellular ATP levels and heterotrophic CO2 assimilation. A weak estrogenic response was detected for MTBE at concentrations ⩾ 3.7 g L(-1) using an estrogen inducible bioluminescent yeast strain (S. cerevisiae BLYES). Microbial hydrolytic enzyme activity in groundwater was affected by MTBE with EC10 values of 0.5-787 mg L(-1), and EC50 values of 59-3073 for alkaline phosphatase, arylsulfatase, beta-1,4-glucanase, N-acetyl-beta-d-glucosaminidase, and leucine-aminopeptidase. Microbial alkaline phosphatase and beta-1,4-glucanase activity were most sensitive to MTBE exposure with EC50 ⩽ 64.8 mg L(-1). The study suggests that bioassays with luminescent A. fischeri, and fluorescent assays targeting hydrolytic enzyme activity are good candidates for monitoring microbial MTBE toxicity in contaminated water. Copyright © 2014 Elsevier Ltd. All rights reserved.

Antiviral activities of extracts and selected pure constituents of Ocimum basilicum.

PubMed

Chiang, Lien-Chai; Ng, Lean-Teik; Cheng, Pei-Win; Chiang, Win; Lin, Chun-Ching

2005-10-01

1. Ocimum basilicum (OB), also known as sweet basil, is a well known medicinal herb in traditional Chinese medicine preparations. In the present study, extracts and purified components of OB were used to identify possible antiviral activities against DNA viruses (herpes viruses (HSV), adenoviruses (ADV) and hepatitis B virus) and RNA viruses (coxsackievirus B1 (CVB1) and enterovirus 71 (EV71)). 2. The results show that crude aqueous and ethanolic extracts of OB and selected purified components, namely apigenin, linalool and ursolic acid, exhibit a broad spectrum of antiviral activity. Of these compounds, ursolic acid showed the strongest activity against HSV-1 (EC50 = 6.6 mg/L; selectivity index (SI) = 15.2), ADV-8 (EC50 = 4.2 mg/L; SI = 23.8), CVB1 (EC50 = 0.4 mg/L; SI = 251.3) and EV71 (EC50 = 0.5 mg/L; SI = 201), whereas apigenin showed the highest activity against HSV-2 (EC50 = 9.7 mg/L; SI = 6.2), ADV-3 (EC50 = 11.1 mg/L; SI = 5.4), hepatitis B surface antigen (EC50 = 7.1 mg/L; SI = 2.3) and hepatitis B e antigen (EC50 = 12.8 mg/L; SI = 1.3) and linalool showed strongest activity against AVD-II (EC50 = 16.9 mg/L; SI = 10.5). 3. No activity was noted for carvone, cineole, beta-caryophyllene, farnesol, fenchone, geraniol, beta-myrcene and alpha-thujone. 4. The action of ursolic acid against CVB1 and EV71 was found to occur during the infection process and the replication phase. 5. With SI values greater than 200, the potential use of ursolic acid for treating infection with CVB1 and EV71 merits further investigation.

Acute toxicity, brine shrimp cytotoxicity and relaxant activity of fruits of callistemon citrinus curtis.

PubMed

Ali, Niaz; Ahmed, Ghayour; Shah, Syed Wadood Ali; Shah, Ismail; Ghias, Mehreen; Khan, Imran

2011-10-24

Callistemon citrinus Curtis belongs to family Myrtaceae that has a great medicinal importance. In our previous work, fruits of Callistemon citrinus were reported to have relaxant (antispasmodic) activity. The current work describes the screening of fractions of the crude methanol extract for tracing spasmolytic constituents so that it shall help us for isolation of bioactive compounds. Acute toxicity and brine shrimp cytotoxicity of crude methanol extract are also performed to standardize it. The crude methanol extract was obtained by maceration with distilled water (500 ml) three times and fractionated successively with n-hexane, chloroform, ethyl acetate and n-butanol (300 ml of each solvent). Phytochemical analysis for crude methanol extract was performed. Acute toxicity studies were performed in mice. Brine shrimp cytotoxicity studies were performed to determine its cytotoxicity and standardize it. In other series of experiments, rabbits' jejunum preparations were used in screening for possible relaxant activities of various fractions. They were applied in concentrations of 0.01, 0.03, 0.1, 0.3, 1.0, 3.0, 5.0 and 10.0 mg/ml on spontaneous rabbits' jejunum preparations. In similar fashion, fractions were also tested on KCl (80 mM) -induced contractions. Calcium chloride curves were constructed in K-rich Tyrode's solution. The effects of various fractions were tested on calcium chloride curves at concentrations 1.0, 3.0, 5.0 and 10.0 mg/ml. Curves of verapamil used as reference drug at concentration 0.1 μM and 0.3 μM were also constructed. The curves were compared with their respective controls for possible right shift. Methanol extract tested strongly positive for saponins and tannins. However, it tested mild positive for presence of proteins, amino acids, carbohydrates and phenolic compounds. LD(50) value for crude methanol extract is 476.25 ± 10.3 (470-481, n = 4) mg/ml. Similarly, EC(50) value for brine shrimp cytotoxicity is 65.5 ± 7.28 (60.8- 69.4, n = 4) mg/ml. All the fractions relaxed the spontaneous and KCl-induced contractions. EC(50) values (mg/ml) for effects of ethyl acetate fraction on spontaneous and KCl induced contractions are 2.62 ± 0.78 (2.15-3.0, n = 4) and 3.72 ± 0.86 (3.38-4.28, n = 4) respectively. Respective EC(50) values (mg/ml) for n-butanol fraction are 3.59 ± 0.2(3.07-3.9, n = 4) for spontaneous, and 5.57 ± 0.2 (5.07-6.11, n = 4) for KCl- induced contractions. EC(50) value for control calcium chloride curve (without extract) is -2.73 ± 0.19 (-2.6 - -2.81, n = 4) while EC(50) for curves treated with 5.0 mg/ml of chloroform is -2.22 ± 0.02 (-2.16 - -2.3, n = 4). EC(50) value for ethyl acetate treated (1.0 mg/ml) tissues is -1.95 ± 0.10 (-1.88 - -2.0, n = 4) vs. control EC(50) = -2.71 ± 0.08 (-2.66 - -2.76, n = 4). All the fractions, except n-hexane, showed a right shift like that of verapamil (EC(50) = -1.72 ± 0.15 (-1.62 - -1.8, n = 4) vs. Control EC(50) = -2.41 ± 0.06 (-2.38 - - 2.44, n = 4), a standard drug that blocks voltage operated calcium channels. Relaxant constituents were more concentrated in ethylacetate fraction followed by chloroform, n -butanol and aqueous fractions that warrant for its isolation. The crude methanol extract is safe at concentration 250 mg/ml or below and results of brine shrimp cytotoxicity assay imply the plant specie may be a source of cytotoxic agents.

Impaired calcium sensing distinguishes primary hyperparathyroidism (PHPT) patients with low bone mineral density.

PubMed

Weber, Thomas J; Koh, James; Thomas, Samantha M; Hogue, Joyce A; Scheri, Randall P; Roman, Sanziana A; Sosa, Julie A

2017-09-01

A subset of PHPT patients exhibit a more severe disease phenotype characterized by bone loss, fractures, recurrent nephrolithiasis, and other dysfunctions, but the underlying reasons for this disparity in clinical presentation remain unknown. We sought to identify new mechanistic indices that could inform more personalized management of PHPT. Pre-, peri-, and postoperative data and demographic, clinical, and pathological information from patients undergoing parathyroidectomy for PHPT were collected. Univariate and partial Spearman correlation was used to estimate the association of parathyroid tumor calcium sensing capacity with select variables. An unselected series of 237 patients aged >18years and undergoing parathyroidectomy for PHPT were enrolled. Calcium sensing capacity, expressed as the concentration required for half-maximal biochemical response (EC50), was evaluated in parathyroid tumors from an unselected series of 74 patients and assessed for association with clinical parameters. The hypothesis was that greater disease severity would be associated with attenuated calcium sensitivity and biochemically autonomous parathyroid tumor behavior. Parathyroid tumors segregated into two distinct groups of calcium responsiveness (EC50<3.0 and ≥3.0mM). The low EC50 group (n=27) demonstrated a mean calcium EC50 value of 2.49mM [95% confidence interval (CI): 2.43-2.54mM], consistent with reference normal activity. In contrast, the high EC50 group (n=47) displayed attenuated calcium sensitivity with a mean EC50 value of 3.48mM [95% CI: 3.41-3.55mM]. Retrospective analysis of the clinical registry data suggested that high calcium EC50 patients presented with a more significant preoperative bone mineral density (BMD) deficit with a t-score of -2.7, (95% CI: -3.4 to -1.9) versus 0.9, (95% CI: -2.1 to -0.4) in low EC50 patients (p<0.001). After adjusting for gender, age, BMI, 25 OH vitamin D level and preoperative iPTH, lowest t-score and calcium EC50 were inversely correlated, with a partial Spearman correlation coefficient of -0.35 (p=0.02). Impaired calcium sensing in parathyroid tumors is selectively observed in a subset of patients with more severe bone mineral density deficit. Assessment of parathyroid tumor biochemical behavior may be a useful predictor of disease severity as measured by bone mineral density in patients with PHPT. Copyright © 2017 Elsevier Inc. All rights reserved.

Mechanism-based pharmacodynamic modeling of the interaction of midazolam, bretazenil, and zolpidem with ethanol.

PubMed

Tuk, Bert; van Gool, Toon; Danhof, Meindert

2002-06-01

The pharmacokinetic and pharmacodynamic interactions of ethanol with the full benzodiazepine agonist midazolam, the partial agonist bretazenil and the benzodiazepine BZ1 receptor subtype selective agonist zolpidem have been determined in the rat in vivo, using an integrated pharmacokinetic-pharmacodynamic approach. Ethanol was administered as a constant rate infusion resulting in constant plasma concentrations of 0.5 g/l. The pharmacokinetics and pharmacodynamics of midazolam, bretazenil, and zolpidem were determined following an intravenous infusion of 5.0, 2.5, and 18 mg/kg respectively. The amplitude in the 11.5-30 Hz frequency band of the EEG was used as measure of the pharmacological effect. For each of the benzodiazepines the concentration-EEG effect relationship could be described by the sigmoid Emax pharmacodynamic model. Significant differences in both EC50 and Emax were observed. The values of the EC50 were 76 +/- 11, 12 +/- 3, and 512 +/- 116 ng/ml for midazolam, bretazenil, and zolpidem respectively. The values of the Emax were 113 +/- 9, 44 +/- 3, and 175 +/- 10 microV/s. In the presence of ethanol the values of the EC50 of midazolam and zolpidem were reduced to approximately 50% of the original value. The values for Emax and Hill-factor were unchanged Due to a large interindividual variability no significant change in EC50 was observed for bretazenil. Analysis of the data on basis of a mechanism-based model showed only a decrease in the apparent affinity constant KPD for all three drugs, indicating that changes in EC50 can be explained entirely by a change in the apparent affinity constant KPD without concomitant changes in the efficacy parameter ePD and the stimulus-effect relationship. The findings of this study show that the pharmacodynamic interactions with a low dose of ethanol in vivo are qualitatively and quantitatively similar for benzodiazepine receptor full agonists, partial agonists, and benzodiazepine BZ1 receptor subtype selective agonists. This interaction can be explained entirely by a change in the affinity of the biological system for each benzodiazepine.

The toxicity of Roundup® 360 SL formulation and its main constituents: glyphosate and isopropylamine towards non-target water photoautotrophs.

PubMed

Lipok, Jacek; Studnik, Hanna; Gruyaert, Steven

2010-10-01

The toxicity of commercial formulation of Roundup® 360 SL, widely used, nonselective herbicide and its main constituents, glyphosate (PMG), equimolar (1:1) isopropylamine salt of glyphosate (GIPA) and isopropylamine (IPA) was examined towards eight aquatic microphotoautotrophs; seven cyanobacterial strains representing either saline or freshwater communities, and common eukaryotic algae Chlorella vulgaris Beijerinck. Autotrophs were cultured 21 days in their appropriate standard media supplemented with various amounts of Roundup®, glyphosate, GIPA and IPA. The determination of the growth of examined photoautotrophs was performed by time-course measurements of total chlorophyll content in experimental cultures. The growth rates related to corresponding concentrations of chemicals, the EC(50) values and generation doubling time were determined in order to present the toxicity Roundup® 360 SL formulation and its main constituents. Market available formulation of Roundup® was found to possess toxicity significantly higher than this, attributed to its main constituents; however both these compounds, isopropylamine and glyphosate, also inhibited the growth of examined strains in a dose-dependent manner. Notably, the interpretation of toxicity of the examined substances was found to be significantly dependent on the method of EC(50) calculation. The choice of molar or weight concentration of substances tested separately and in specific formulation was found to be essential in this matter. Due to these findings the EC(50) values were calculated based either on molar or on weight concentrations. Considering Roundup® 360 SL formulation, these values ranged from 10(-3) up to 10(-1) mM and they were one order of magnitude lower than those found for isopropylamine. Quite surprisingly the minimum EC(50) values found for glyphosate did not reach micromolar concentrations, whereas most of the EC(50) values revealed to IPA did not exceed this range. Notably, in all the cases except for Synechocystis aquatilis Sauvageau, isopropylamine alone was indicated as more toxic than glyphosate. Copyright © 2010 Elsevier Inc. All rights reserved.

Novel Tandem Biotransformation Process for the Biosynthesis of a Novel Compound, 4-(2,3,5,6-Tetramethylpyrazine-1)-4′-Demethylepipodophyllotoxin▿

PubMed Central

Tang, Ya-Jie; Zhao, Wei; Li, Hong-Mei

2011-01-01

According to the structure of podophyllotoxin and its structure-function relationship, a novel tandem biotransformation process was developed for the directional modification of the podophyllotoxin structure to directionally synthesize a novel compound, 4-(2,3,5,6-tetramethylpyrazine-1)-4′-demethylepipodophyllotoxin (4-TMP-DMEP). In this novel tandem biotransformation process, the starting substrate of podophyllotoxin was biotransformed into 4′-demethylepipodophyllotoxin (product 1) with the demethylation of the methoxyl group at the 4′ position by Gibberella fujikuroi SH-f13, which was screened out from Shennongjia prime forest humus soil (Hubei, China). 4′-Demethylepipodophyllotoxin (product 1) was then biotransformed into 4′-demethylpodophyllotoxone (product 2) with the oxidation of the hydroxyl group at the 4 position by Alternaria alternata S-f6, which was screened out from the gathered Dysosma versipellis plants in the Wuhan Botanical Garden, Chinese Academy of Sciences. Finally, 4′-demethylpodophyllotoxone (product 2) and ligustrazine were linked with a transamination reaction to synthesize the target product 4-TMP-DMEP (product 3) by Alternaria alternata S-f6. Compared with podophyllotoxin (i.e., a 50% effective concentration [EC50] of 529 μM), the EC50 of 4-TMP-DMEP against the tumor cell line BGC-823 (i.e., 0.11 μM) was significantly reduced by 5,199 times. Simultaneously, the EC50 of 4-TMP-DMEP against the normal human proximal tubular epithelial cell line HK-2 (i.e., 0.40 μM) was 66 times higher than that of podophyllotoxin (i.e., 0.006 μM). Furthermore, compared with podophyllotoxin (i.e., log P = 0.34), the water solubility of 4-TMP-DMEP (i.e., log P = 0.66) was significantly enhanced by 94%. For the first time, the novel compound 4-TMP-DMEP with superior antitumor activity was directionally synthesized from podophyllotoxin by the novel tandem biotransformation process developed in this work. PMID:21398491

Single- and mixture toxicity of three organic UV-filters, ethylhexyl methoxycinnamate, octocrylene, and avobenzone on Daphnia magna.

PubMed

Park, Chang-Beom; Jang, Jiyi; Kim, Sanghun; Kim, Young Jun

2017-03-01

In freshwater environments, aquatic organisms are generally exposed to mixtures of various chemical substances. In this study, we tested the toxicity of three organic UV-filters (ethylhexyl methoxycinnamate, octocrylene, and avobenzone) to Daphnia magna in order to evaluate the combined toxicity of these substances when in they occur in a mixture. The values of effective concentrations (ECx) for each UV-filter were calculated by concentration-response curves; concentration-combinations of three different UV-filters in a mixture were determined by the fraction of components based on EC 25 values predicted by concentration addition (CA) model. The interaction between the UV-filters were also assessed by model deviation ratio (MDR) using observed and predicted toxicity values obtained from mixture-exposure tests and CA model. The results from this study indicated that observed ECx mix (e.g., EC 10mix , EC 25mix , or EC 50mix ) values obtained from mixture-exposure tests were higher than predicted ECx mix (e.g., EC 10mix , EC 25mix , or EC 50mix ) values calculated by CA model. MDR values were also less than a factor of 1.0 in a mixtures of three different UV-filters. Based on these results, we suggest for the first time a reduction of toxic effects in the mixtures of three UV-filters, caused by antagonistic action of the components. Our findings from this study will provide important information for hazard or risk assessment of organic UV-filters, when they existed together in the aquatic environment. To better understand the mixture toxicity and the interaction of components in a mixture, further studies for various combinations of mixture components are also required. Copyright © 2016 Elsevier Inc. All rights reserved.

In vitro antiviral activities of Caesalpinia pulcherrima and its related flavonoids.

PubMed

Chiang, L C; Chiang, W; Liu, M C; Lin, C C

2003-08-01

The aim of this study was to search for new antiviral agents from Chinese herbal medicine. Pure flavonoids and aqueous extracts of Caesalpinia pulcherrima Swartz were used in experiments to test their influence on a series of viruses, namely herpesviruses (HSV-1, HSV-2) and adenoviruses (ADV-3, ADV-8, ADV-11). The EC50 was defined as the concentration required to achieve 50% protection against virus-induced cytopathic effects, and the selectivity index (SI) was determined as the ratio of CC50 (concentration of 50% cellular cytotoxicity) to EC50. Results showed that aqueous extracts of C. pulcherrima and its related quercetin possessed a broad-spectrum antiviral activity. Among them, the strongest activities against ADV-8 were fruit and seed (EC50 = 41.2 mg/l, SI = 83.2), stem and leaf (EC50 = 61.8 mg/l, SI = 52.1) and flower (EC50 = 177.9 mg/l, SI = 15.5), whereas quercetin possessed the strongest anti-ADV-3 activity (EC50 = 24.3 mg/l, SI = 20.4). In conclusion, some compounds of C. pulcherrima which possess antiviral activities may be derived from the flavonoid of quercetin. The mode of action of quercetin against HSV-1 and ADV-3 was found to be at the early stage of multiplication and with SI values greater than 20, suggesting the potential use of this compound for treatment of the infection caused by these two viruses.

Toxicities of triclosan, phenol, and copper sulfate in activated sludge.

PubMed

Neumegen, Rosalind A; Fernández-Alba, Amadeo R; Chisti, Yusuf

2005-04-01

The effect of toxicants on the BOD degradation rate constant was used to quantitatively establish the toxicity of triclosan, phenol, and copper (II) against activated sludge microorganisms. Toxicities were tested over the following ranges of concentrations: 0-450 mg/L for phenol, 0-2 mg/L for triclosan, and 0-35 mg/L for copper sulfate (pentahydrate). According to the EC(50) values, triclosan was the most toxic compound tested (EC(50) = 1.82 +/- 0.1 mg/L), copper (II) had intermediate toxicity (EC(50) = 18.3 +/- 0.37 mg/L), and phenol was the least toxic (EC(50) = 270 +/- 0.26 mg/L). The presence of 0.2% DMSO had no toxic effect on the activated sludge. The toxicity evaluation method used was simple, reproducible, and directly relevant to activated sludge wastewater treatment processes.

Interactions of pyrethroid insecticides with GABA sub A and peripheral-type benzodiazepine receptors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Devaud, L.L.

1988-01-01

Pyrethroid insecticides are potent proconvulsants in the rat. All pyrethroids evincing proconvulsant activity elicited a similar 25-30% maximal reduction of seizure threshold. The Type II pyrethroids were the most potent proconvulsants with 1R{alpha}S, cis cypermethrin having an ED{sub 50} value of 6.3 nmol/kg. The proconvulsant activity of both Type I and Type II pyrenthroids was blocked by pretreatment with PK 11195, the peripheral-type benzodiazepine receptor (PTBR) antagonist. In contrast, phenytoin did not antagonize the proconvulsant activity of either deltamethrin or permethrin. Pyrethroids displaced the specific binding of ({sup 3}H)Ro5-4864 to rat brain membranes with a significant correlation between the logmore » EC{sub 50} values for their activities as proconvulsants and the log IC{sub 50} values for their inhibition of ({sup 3}H)Ro5-4864 binding. Both Ro5-4864 and pyrethroid insecticides were found to influence specific ({sup 35}S)TBPS binding in a GABA-dependent manner. PK 11195 and the Type II pyrethroid, deltamethrin antagonized the Ro5-4864-induced modulation of ({sup 35}S)TBPS binding. Pyrethroid insecticides, Ro5-4864 and veratridine influenced GABA-gated {sup 36}Chloride influx. Moreover, the Type II pyrethroids elicited an increase in {sup 36}chloride influx in the absence of GABA-stimulation. Both of these actions were antagonized by PK 11195 and tetrodotoxin.« less

Fractionation and antioxidant activity potency of the extract of Garcinia lateriflora Blume var. javanica Boerl leaf

NASA Astrophysics Data System (ADS)

Mahayasih, Putu Gita Maya Widyaswari; Elya, Berna; Hanafi, Muhammad

2018-02-01

Garcinia lateriflora leaves extract of the family Guttiferae has been known to have excellent antioxidant activity. The objective of the study was to determine the antioxidant effect of the n-hexane, ethyl acetate and methanol extracts of G. lateriflora leaves extract. The antioxidant activity was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging methods and Feric Reducing Antioxidant Power (FRAP) to determine the antioxidant properties. The extracts were fractionated by using column chromatography. The Methanol extract exhibited the strongest antioxidant activity with EC50 values are 13.95 and 19.65 µg/mL by DPPH and FRAP methods respectively. E13 fraction was the most active fraction from ethyl acetate extract with EC50 value for DPPH scavenging method was 37.14 µg/mL and 34.46 µg/mL for reducing power by the FRAP method. Meanwhile M3 fraction was the most active fraction in methanol extract with EC50 value for DPPH scavenging method was 50.02 µg/mL and 37.32 µg/mL for reducing power by the FRAP method.

Comparative molecular field analysis to derive pharmacophore maps for induction doses of intravenous anaesthetic agents.

PubMed

Sear, J W

2011-03-01

The present study examines the molecular basis of induction of anaesthesia by i.v. hypnotic agents using comparative molecular field analysis (CoMFA). ED(50) induction doses for 14 i.v. anaesthetics in human subjects (expressed as molar dose per kilogram body weight) were obtained from the literature. Immobilizing potency data for the same 14 agents (expressed as the EC(50) plasma free drug concentrations that abolish movement in response to a noxious stimulus in 50% patients) were taken from our previous publication. These data were used to form CoMFA models for the two aspects of anaesthetic activity. Molecular alignment was achieved by field-fit minimization techniques. The lead structure for both models was eltanolone. The final CoMFA model for the ED(50) induction dose was based on two latent variables, and explained 99.3% of the variance in observed activities. It showed good intrinsic predictability (cross-validated q(2)=0.849). The equivalent model for immobilizing activity was also based on two latent variables, with r(2)=0.988 and q(2)=0.852. Although there was a correlation between -log ED(50) and -log EC(50) (r(2)=0.779), comparison of the pharmacophore maps showed poor correlation for both electrostatic and steric regions when isocontours were constructed by linking lattice grid points, making the greatest 40% contributions; the relative contributions of electrostatic and steric interactions differing between the models (induction dose: 2.5:1; immobilizing activity 1.8:1). Comparison of two CoMFA activity models shows only small elements of commonality, suggesting that different molecular features may be responsible for these two properties of i.v. anaesthetics.

EC03089-6421: a new, very rapidly pulsating sdO star

NASA Astrophysics Data System (ADS)

Kilkenny, D.; Worters, H. L.; Østensen, R. H.

2017-06-01

EC 03089-6421, classified sdO in the Edinburgh-Cape (EC) blue object survey, is shown to have unusually rapid pulsations with a dominant frequency near 32 mHz (amplitude ˜0.02 mag; period 31.1 s) - which appears to be strongly variable in amplitude on time-scales of hours and days - and a generally weaker frequency near 29 mHz (amplitude ˜0.004 mag; period 34.2 s), which is also variable in amplitude. This star varies at twice the frequency of any known hot subdwarf pulsator. Although the low-resolution EC spectrogram appears very similar to those of DAO stars, our analysis derives Teff = 40 200 ± 1600 K; log g = 6.25 ± 0.23 and log N(He)/N(H) = -1.63 ± 0.55; more recent spectrograms give Teff = 37 400 ± 1000 K; log g = 5.70 ± 0.13 and log N(He)/N(H) = -2.02 ± 0.17, both of which indicate that the gravity is too low for a white dwarf star, although the low temperature derived from the Balmer lines is at odds with the absence of neutral Helium and the strength of He II 4686. It is possible that EC 03089-6421 is a field analogue of the ω Cen sdO variables.

Developmental toxicity of p,p'-dichlorodiphenyltrichloroethane, 2,4,6-trinitrotoluene, their metabolites, and benzo[a]pyrene in Xenopus laevis embryos.

PubMed

Saka, Masahiro

2004-04-01

Since 1995, high incidences of deformed frogs have been documented in Kitakyushu, Japan. In this area, relatively high concentrations of DDT, trinitrotoluene (TNT), their metabolites (p,p'-dichlorodiphenyldichloroethylene [DDE], p,p'-dichlorodiphenyldichloroethane [DDD], 2-amino-4,6-dinitrotoluene [2ADNT], and 4-amino-2,6-dinitrotoluene [4ADNT]), and benzo[a]pyrene [BaP]) have been identified from field samples. I used a standardized assay with Xenopus laevis embryos (frog embryo teratogenesis assay--Xenopus, FETAX) to examine the developmental toxicity of these compounds. Both DDE and BaP were considered nearly nontoxic in embryonic development because they induced low (< 10%) mortality and malformation incidence even at the highest concentrations tested (DDE, 393 microM; BaP, 13.2 microM). The DDD (96-h median lethal concentration [LC50] = 44.1 microM, 96-h median effective concentration [EC50] for malformation = 14.9 microM) was more lethal and teratogenic than its parent compound, DDT (96-h LC50 = 101 microM, 96-h EC50 = 41.5 microM). Predominant symptoms observed were axial malformations (DDT and DDD) and irregular gut coiling (DDT). However, DDT and DDD should not act as major lethal or teratogenic toxicants in the aquatic environment within a short-term exposure via water because their 96-h LC50 and 96-h EC50 values were extremely high, considering their low solubility in water. The TNT (96-h LC50 = 16.7 microM) was more lethal than 2ADNT (96-h LC50 = 166 microM) or 4ADNT (96-h LC50 = 115 microM). Although 4ADNT (96-h EC50 = 85.8 microM) induced various tadpole malformations, it was a weak teratogen compared with TNT (96-h EC50 = 9.78 microM) and 2ADNT (96-h EC50 = 16.9 microM). The most typical malformations observed were axial malformations, eye abnormalities (TNT), edema, and irregular gut coiling (2ADNT and 4ADNT). The 96-h LC50 and 96-h EC50 values of TNT, 2ADNT, and 4ADNT were lower than their saturated concentrations in water. Therefore, these nitroaromatic compounds may show lethal or teratogenic effects on aquatic animals if their habitats are severely contaminated with TNT.

In Vitro Antiviral Activity and Resistance Profile Characterization of the Hepatitis C Virus NS5A Inhibitor Ledipasvir.

PubMed

Cheng, Guofeng; Tian, Yang; Doehle, Brian; Peng, Betty; Corsa, Amoreena; Lee, Yu-Jen; Gong, Ruoyu; Yu, Mei; Han, Bin; Xu, Simin; Dvory-Sobol, Hadas; Perron, Michel; Xu, Yili; Mo, Hongmei; Pagratis, Nikos; Link, John O; Delaney, William

2016-01-11

Ledipasvir (LDV; GS-5885), a component of Harvoni (a fixed-dose combination of LDV with sofosbuvir [SOF]), is approved to treat chronic hepatitis C virus (HCV) infection. Here, we report key preclinical antiviral properties of LDV, including in vitro potency, in vitro resistance profile, and activity in combination with other anti-HCV agents. LDV has picomolar antiviral activity against genotype 1a and genotype 1b replicons with 50% effective concentration (EC50) values of 0.031 nM and 0.004 nM, respectively. LDV is also active against HCV genotypes 4a, 4d, 5a, and 6a with EC50 values of 0.11 to 1.1 nM. LDV has relatively less in vitro antiviral activity against genotypes 2a, 2b, 3a, and 6e, with EC50 values of 16 to 530 nM. In vitro resistance selection with LDV identified the single Y93H and Q30E resistance-associated variants (RAVs) in the NS5A gene; these RAVs were also observed in patients after a 3-day monotherapy treatment. In vitro antiviral combination studies indicate that LDV has additive to moderately synergistic antiviral activity when combined with other classes of HCV direct-acting antiviral (DAA) agents, including NS3/4A protease inhibitors and the nucleotide NS5B polymerase inhibitor SOF. Furthermore, LDV is active against known NS3 protease and NS5B polymerase inhibitor RAVs with EC50 values equivalent to those for the wild type. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

In Vitro Antiviral Activity and Resistance Profile Characterization of the Hepatitis C Virus NS5A Inhibitor Ledipasvir

PubMed Central

Tian, Yang; Doehle, Brian; Peng, Betty; Corsa, Amoreena; Lee, Yu-Jen; Gong, Ruoyu; Yu, Mei; Han, Bin; Xu, Simin; Dvory-Sobol, Hadas; Perron, Michel; Xu, Yili; Mo, Hongmei; Pagratis, Nikos; Link, John O.; Delaney, William

2016-01-01

Ledipasvir (LDV; GS-5885), a component of Harvoni (a fixed-dose combination of LDV with sofosbuvir [SOF]), is approved to treat chronic hepatitis C virus (HCV) infection. Here, we report key preclinical antiviral properties of LDV, including in vitro potency, in vitro resistance profile, and activity in combination with other anti-HCV agents. LDV has picomolar antiviral activity against genotype 1a and genotype 1b replicons with 50% effective concentration (EC50) values of 0.031 nM and 0.004 nM, respectively. LDV is also active against HCV genotypes 4a, 4d, 5a, and 6a with EC50 values of 0.11 to 1.1 nM. LDV has relatively less in vitro antiviral activity against genotypes 2a, 2b, 3a, and 6e, with EC50 values of 16 to 530 nM. In vitro resistance selection with LDV identified the single Y93H and Q30E resistance-associated variants (RAVs) in the NS5A gene; these RAVs were also observed in patients after a 3-day monotherapy treatment. In vitro antiviral combination studies indicate that LDV has additive to moderately synergistic antiviral activity when combined with other classes of HCV direct-acting antiviral (DAA) agents, including NS3/4A protease inhibitors and the nucleotide NS5B polymerase inhibitor SOF. Furthermore, LDV is active against known NS3 protease and NS5B polymerase inhibitor RAVs with EC50 values equivalent to those for the wild type. PMID:26824950

Effects of five antifouling biocides on settlement and growth of zoospores from the marine macroalga Ulva lactuca L.

PubMed

Wendt, Ida; Arrhenius, Åsa; Backhaus, Thomas; Hilvarsson, Annelie; Holm, Kristina; Langford, Katherine; Tunovic, Timur; Blanck, Hans

2013-10-01

Antifouling biocides are found in the marine ecosystem were they can affect non-target organisms. In this study the effects of five antifouling biocides on the settlement and growth of Ulva lactuca zoospores were investigated. The biocides investigated were copper (Cu(2+)), 4,5-dichloro-2-n-octyl-3(2H)-isothiazolone (DCOIT), triphenylborane pyridine (TPBP), tolylfluanid and medetomidine. Full concentration-response curves where determined for each compound. EC50 values were determined for copper, DCOIT, TPBP and tolylfluanid, all of which inhibited settlement and growth in a concentration dependent manner with the following toxicity ranking; tolylfluanid (EC50 80 nmol L(-1)) ~ DCOIT (EC50 83 nmol L(-1)) > TPBP (EC50 400 nmol L(-1)) > Cu(2+) (EC50 2,000 nmol L(-1)). Medetomidine inhibited settlement and growth only at the extreme concentration of 100,000 nmol L(-1) (93% effect). The low toxicity is possibly a consequence of a lack of receptors that medetomidine can bind to in the U. lactuca zoospores.

Fused heterocycles bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 4: design, synthesis and biological evaluation of novel imidazo[1,2-a]pyrazines.

PubMed

Huang, Boshi; Liang, Xin; Li, Cuicui; Chen, Wenmin; Liu, Tao; Li, Xiao; Sun, Yueyue; Fu, Lu; Liu, Huiqing; De Clercq, Erik; Pannecouque, Christophe; Zhan, Peng; Liu, Xinyong

2015-03-26

Through a structure-guided core-refining approach, a series of novel imidazo[1,2-a]pyrazine derivatives were designed, synthesized and evaluated as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Biological results of antiviral assay in MT-4 cell cultures showed that 12 target compounds displayed moderate activities against wild-type (wt) HIV-1 strain (IIIB) with EC50 values ranging from 0.26 μM to 19 μM. Among them, 4a and 5a were found to be the two most active analogues possessing EC50 values of 0.26 μM and 0.32 μM respectively, comparable to delavirdine (DLV, EC50 = 0.54 μM) and nevirapine (NVP, EC50 = 0.31 μM) in a cell-based assay. Additionally, 9 compounds showed RT inhibitory activity superior to that of NVP. Moreover, some predicted drug-like properties of representative compounds 4a and 5a, as well as the structure-activity relationship (SAR) analysis were discussed in detail. The binding mode of compound 4a was investigated by molecular simulation studies. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Mechanisms of action of (meth)acrylates in hemolytic activity, in vivo toxicity and dipalmitoylphosphatidylcholine (DPPC) liposomes determined using NMR spectroscopy.

PubMed

Fujisawa, Seiichiro; Kadoma, Yoshinori

2012-01-01

We investigated the quantitative structure-activity relationships between hemolytic activity (log 1/H(50)) or in vivo mouse intraperitoneal (ip) LD(50) using reported data for α,β-unsaturated carbonyl compounds such as (meth)acrylate monomers and their (13)C-NMR β-carbon chemical shift (δ). The log 1/H(50) value for methacrylates was linearly correlated with the δC(β) value. That for (meth)acrylates was linearly correlated with log P, an index of lipophilicity. The ipLD(50) for (meth)acrylates was linearly correlated with δC(β) but not with log P. For (meth)acrylates, the δC(β) value, which is dependent on the π-electron density on the β-carbon, was linearly correlated with PM3-based theoretical parameters (chemical hardness, η; electronegativity, χ; electrophilicity, ω), whereas log P was linearly correlated with heat of formation (HF). Also, the interaction between (meth)acrylates and DPPC liposomes in cell membrane molecular models was investigated using (1)H-NMR spectroscopy and differential scanning calorimetry (DSC). The log 1/H(50) value was related to the difference in chemical shift (ΔδHa) (Ha: H (trans) attached to the β-carbon) between the free monomer and the DPPC liposome-bound monomer. Monomer-induced DSC phase transition properties were related to HF for monomers. NMR chemical shifts may represent a valuable parameter for investigating the biological mechanisms of action of (meth)acrylates.

Mechanisms of Action of (Meth)acrylates in Hemolytic Activity, in Vivo Toxicity and Dipalmitoylphosphatidylcholine (DPPC) Liposomes Determined Using NMR Spectroscopy

PubMed Central

Fujisawa, Seiichiro; Kadoma, Yoshinori

2012-01-01

We investigated the quantitative structure-activity relationships between hemolytic activity (log 1/H50) or in vivo mouse intraperitoneal (ip) LD50 using reported data for α,β-unsaturated carbonyl compounds such as (meth)acrylate monomers and their 13C-NMR β-carbon chemical shift (δ). The log 1/H50 value for methacrylates was linearly correlated with the δCβ value. That for (meth)acrylates was linearly correlated with log P, an index of lipophilicity. The ipLD50 for (meth)acrylates was linearly correlated with δCβ but not with log P. For (meth)acrylates, the δCβ value, which is dependent on the π-electron density on the β-carbon, was linearly correlated with PM3-based theoretical parameters (chemical hardness, η; electronegativity, χ; electrophilicity, ω), whereas log P was linearly correlated with heat of formation (HF). Also, the interaction between (meth)acrylates and DPPC liposomes in cell membrane molecular models was investigated using 1H-NMR spectroscopy and differential scanning calorimetry (DSC). The log 1/H50 value was related to the difference in chemical shift (ΔδHa) (Ha: H (trans) attached to the β-carbon) between the free monomer and the DPPC liposome-bound monomer. Monomer-induced DSC phase transition properties were related to HF for monomers. NMR chemical shifts may represent a valuable parameter for investigating the biological mechanisms of action of (meth)acrylates. PMID:22312284

Comparing the sensitivity of chlorophytes, cyanobacteria, and diatoms to major-use antibiotics.

PubMed

Guo, Jiahua; Selby, Katherine; Boxall, Alistair B A

2016-10-01

The occurrence of antibiotic residues in the aquatic environment is an emerging concern. In contrast to daphnia and fish, algae are known to be particularly sensitive to antibiotic exposure. However, to date, a systematic evaluation of the sensitivity of different algal species to antibiotics has not been performed. The aim of the present study was therefore to explore the sensitivity of a battery of algal species toward antibiotic exposures. The present study investigated the growth inhibition effects of 3 major-use antibiotics, tylosin, lincomycin, and trimethoprim, on 7 algal species from the chlorophyte, cyanobacteria, and diatom groups. Based on median effective concentration (EC50) values, cyanobacteria (EC50 = 0.095-0.13 μmol/L) were found to be the most sensitive group to lincomycin followed by chlorophytes (EC50 = 7.36-225.73 μmol/L) and diatoms (EC50 > 225.73 μmol/L). Cyanobacteria were also the most sensitive group to tylosin (EC50 = 0.09-0.092 μmol/L), but, for this compound, diatoms (EC50 = 1.33-5.7 μmol/L) were more sensitive than chlorophytes (EC50 = 4.14-81.2 μmol/L). Diatoms were most sensitive to trimethoprim (EC50 = 7.36-74.61 μmol/L), followed by cyanobacteria (EC50 = 315.78-344.45 μmol/L), and chlorophytes (EC50 > 344.45 μmol/L) for trimethoprim. Although these results partly support the current approach to regulatory environmental risk assessment (whereby cyanobacterial species are recommended for use with antibiotic compounds), they indicate that for some antibiotics this group might not be the most appropriate test organism. It is therefore suggested that environmental risk assessments consider data on 3 algal groups (chlorophytes, cyanobacteria, and diatoms) and use test species from these groups, which are consistently found to be the most sensitive (Pseudokirchneriella subcapitata, Anabaena flos-aquae, and Navicula pelliculosa). Environ Toxicol Chem 2016;35:2587-2596. © 2016 SETAC. © 2016 SETAC.

Using electrical resistivity tomography to assess the effectiveness of managed aquifer recharge in a salinized coastal aquifer.

PubMed

García-Menéndez, Olga; Ballesteros, Bruno J; Renau-Pruñonosa, Arianna; Morell, Ignacio; Mochales, Tania; Ibarra, Pedro I; Rubio, Félix M

2018-01-27

Over 40 years, the detrital aquifer of the Plana de Castellón (Spanish Mediterranean coast) has been subjected to seawater intrusion because of long dry periods combined with intensive groundwater exploitation. Against this backdrop, a managed artificial recharge (MAR) scheme was implemented to improve the groundwater quality. The large difference between the electrical conductivity (EC) of the ambient groundwater (brackish water due to marine intrusion) and the recharge water (freshwater) meant that there was a strong contrast between the resistivities of the brackish water saturated zone and the freshwater saturated zone. Electrical resistivity tomography (ERT) can be used for surveying similar settings to evaluate the effectiveness of artificial recharge schemes. By integrating geophysical data with lithological information, EC logs from boreholes, and hydrochemical data, we can interpret electrical resistivity (ER) with groundwater EC values and so identify freshwater saturated zones. Using this approach, ERT images provided a high-resolution spatial characterization and an accurate picture of the shape and extent of the recharge plume of the MAR site. After 5 months of injection, a freshwater plume with an EC of 400-600 μS/cm had formed that extended 400 m in the W-E direction, 250 m in the N-S direction, and to a depth of 40 m below piezometric level. This study also provides correlations between ER values with different lithologies and groundwater EC values that can be used to support other studies.

Role of exposure mode in the bioavailability of triphenyl phosphate to aquatic organisms

USGS Publications Warehouse

Huckins, James N.; Fairchild, James F.; Boyle, Terence P.

1991-01-01

A laboratory study was conducted to investigate the role of the route of triphenyl phosphate (TPP) entry on its aquatic bioavailability and acute biological effects. Three TPP treatments were used for exposures of fish and invertebrates. These consisted of TPP dosed directly into water with and without clean sediment and TPP spiked onto sediment prior to aqueous exposures. Results of static acute toxicity tests (no sediment) were 0.78 mg/L (96-h LC50) for bluegill, 0.36 mg/L (48-h EC50) for midge, and 0.25 mg/L (96-h EC50) for scud. At 24 h, the sediment (1.1% organic carbon)/water partition coefficient (Kp) for TPP was 112. Use of this partition coefficient model to predict the sediment-mediated reduction of TPP concentration in water during toxicity tests resulted in a value that was only 10% less than the nominal value. However, the required nominal concentration of TPP to cause acute toxicity responses in test organisms was significantly higher than the predicted value by the model for both clay and soil-derived sediment. Direct spiking of TPP to soil minimized TPP bioavailability. Data from parallel experiments designed to track TPP residues in water through time suggest that sorption kinetics control residue bioavailability in the initial 24 h of exposure and may account for observed differences in LC50 and EC50 values from the sediment treatments.

Synthesis of Artemisinin-Derived Dimers, Trimers and Dendrimers: Investigation of Their Antimalarial and Antiviral Activities Including Putative Mechanisms of Action.

PubMed

Fröhlich, Tony; Hahn, Friedrich; Belmudes, Lucid; Leidenberger, Maria; Friedrich, Oliver; Kappes, Barbara; Couté, Yohann; Marschall, Manfred; Tsogoeva, Svetlana B

2018-06-07

Generation of dimers, trimers and dendrimers of bioactive compounds is an approach that has recently been developed for the discovery of new potent drug candidates. Herein, we present the synthesis of new artemisinin-derived dimers and dendrimers and investigate their action against malaria parasite Plasmodium falciparum 3D7 strain and human cytomegalovirus (HCMV). Dimer 7 was the most active compound (EC 50 1.4 nm) in terms of antimalarial efficacy and was even more effective than the standard drugs dihydroartemisinin (EC 50 2.4 nm), artesunic acid (EC 50 8.9 nm) and chloroquine (EC 50 9.8 nm). Trimer 4 stood out as the most active agent against HCMV in vitro replication and exerted an EC 50 value of 0.026 μm, representing an even higher activity than the two reference drugs ganciclovir (EC 50 2.60 μm) and artesunic acid (EC 50 5.41 μm). In addition, artemisinin-derived dimer 13 and trimer 15 were for the first time both immobilized on TOYOPEARL AF-Amino-650M beads and used for mass spectrometry-based target identification experiments using total lysates of HCMV-infected primary human fibroblasts. Two major groups of novel target candidates, namely cytoskeletal and mitochondrial proteins were obtained. Two putatively compound-binding viral proteins, namely major capsid protein (MCP) and envelope glycoprotein pUL132, which are both essential for HCMV replication, were identified. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Randomized, Placebo-Controlled, Single-Ascending-Dose Study of BMS-791325, a Hepatitis C Virus (HCV) NS5B Polymerase Inhibitor, in HCV Genotype 1 Infection

PubMed Central

Lemm, Julie; Eley, Timothy; Liu, Menping; Berglind, Anna; Sherman, Diane; Lawitz, Eric; Vutikullird, Apinya B.; Tebas, Pablo; Gao, Min; Pasquinelli, Claudio; Grasela, Dennis M.

2014-01-01

BMS-791325 is a nonnucleoside inhibitor of hepatitis C virus (HCV) NS5B polymerase with low-nanomolar potency against genotypes 1a (50% effective concentration [EC50], 3 nM) and 1b (EC50, 7 nM) in vitro. BMS-791325 safety, pharmacokinetics, and antiviral activity were evaluated in a double-blind, placebo-controlled, single-ascending-dose study in 24 patients (interferon naive and experienced) with chronic HCV genotype 1 infection, randomized (5:1) to receive a single dose of BMS-791325 (100, 300, 600, or 900 mg) or placebo. The prevalence and phenotype of HCV variants at baseline and specific posttreatment time points were assessed. Antiviral activity was observed in all cohorts, with a mean HCV RNA decline of ≈2.5 log10 copies/ml observed 24 h after a single 300-mg dose. Mean plasma half-life among cohorts was 7 to 9 h; individual 24-hour levels exceeded the protein-adjusted EC90 for genotype 1 at all doses. BMS-791325 was generally well tolerated, with no serious adverse events or discontinuations. Enrichment for resistance variants was not observed at 100 to 600 mg. At 900 mg, variants (P495L/S) associated with BMS-791325 resistance in vitro were transiently observed in one patient, concurrent with an observed HCV RNA decline of 3.4 log10 IU/ml, but were replaced with wild type by 48 h. Single doses of BMS-791325 were well tolerated; demonstrated rapid, substantial, and exposure-related antiviral activity; displayed dose-related increases in exposure; and showed viral kinetic and pharmacokinetic profiles supportive of once- or twice-daily dosing. These results support its further development in combination with other direct-acting antivirals for HCV genotype 1 infection. (This trial has been registered at ClinicalTrials.gov under registration no. NCT00664625.) PMID:24733462

Functionalization of yogurts with Agaricus bisporus extracts encapsulated in spray-dried maltodextrin crosslinked with citric acid.

PubMed

Francisco, Cristhian R L; Heleno, Sandrina A; Fernandes, Isabel P M; Barreira, João C M; Calhelha, Ricardo C; Barros, Lillian; Gonçalves, Odinei Hess; Ferreira, Isabel C F R; Barreiro, Maria Filomena

2018-04-15

Mushroom extracts contain bioactive compounds potentially useful to functionalize foodstuffs. Herein, alcoholic extracts of Agaricus bisporus were studied for their bioactivity and viability as functional ingredients in a food product with high water content (yogurt). Extracts were microencapsulated (to improve their stability and hydrophilicity) by spray-drying, using maltodextrin crosslinked with citric acid as encapsulating material. The effect of thermal treatment (after atomization) on crosslinking and bioactivity of microspheres was tested. The incorporation of free and thermally untreated forms resulted in yogurts with higher initial antioxidant activity (EC 50 values: 214 and 272 mg.mL -1 ) that decreased after 7 days (EC 50 values: 248 and 314 mg.mL -1 ). Contrarily, thermally treated microencapsulated extracts showed higher antioxidant activity after the same period (EC 50 values, 0 days: 106 mg.mL -1 ; 7 days: 48.7 mg.mL -1 ), in result of an effective protection provided by microencapsulation with crosslinked maltodextrin and citric acid. Functionalized yogurts showed an overall maintenance of nutritional properties. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biodegradability and toxicity assessment of a real textile wastewater effluent treated by an optimized electrocoagulation process.

PubMed

Manenti, Diego R; Módenes, Aparecido N; Soares, Petrick A; Boaventura, Rui A R; Palácio, Soraya M; Borba, Fernando H; Espinoza-Quiñones, Fernando R; Bergamasco, Rosângela; Vilar, Vítor J P

2015-01-01

In this work, the application of an iron electrode-based electrocoagulation (EC) process on the treatment of a real textile wastewater (RTW) was investigated. In order to perform an efficient integration of the EC process with a biological oxidation one, an enhancement in the biodegradability and low toxicity of final compounds was sought. Optimal values of EC reactor operation parameters (pH, current density and electrolysis time) were achieved by applying a full factorial 3(3) experimental design. Biodegradability and toxicity assays were performed on treated RTW samples obtained at the optimal values of: pH of the solution (7.0), current density (142.9 A m(-2)) and different electrolysis times. As response variables for the biodegradability and toxicity assessment, the Zahn-Wellens test (Dt), the ratio values of dissolved organic carbon (DOC) relative to low-molecular-weight carboxylates anions (LMCA) and lethal concentration 50 (LC50) were used. According to the Dt, the DOC/LMCA ratio and LC50, an electrolysis time of 15 min along with the optimal values of pH and current density were suggested as suitable for a next stage of treatment based on a biological oxidation process.

Toxicity of marine pollutants on the ascidian oocyte physiology: an electrophysiological approach.

PubMed

Gallo, Alessandra

2018-02-01

In marine animals with external fertilization, gametes are released into seawater where fertilization and embryo development occur. Consequently, pollutants introduced into the marine environment by human activities may affect gametes and embryos. These xenobiotics can alter cell physiology with consequent reduction of fertilization success. Here the adverse effects on the reproductive processes of the marine invertebrate Ciona intestinalis (ascidian) of different xenobiotics: lead, zinc, an organic tin compound and a phenylurea herbicide were evaluated. By using the electrophysiological technique of whole-cell voltage clamping, the effects of these compounds on the mature oocyte plasma membrane electrical properties and the electrical events of fertilization were tested by calculating the concentration that induced 50% normal larval formation (EC50). The results demonstrated that sodium currents in mature oocytes were reduced in a concentration-dependent manner by all tested xenobiotics, with the lowest EC50 value for lead. In contrast, fertilization current frequencies were differently affected by zinc and organic tin compound. Toxicity tests on gametes demonstrated that sperm fertilizing capability and fertilization oocyte competence were not altered by xenobiotics, whereas fertilization was inhibited in zinc solution and underwent a reduction in organic tin compound solution (EC50 value of 1.7 µM). Furthermore, fertilized oocytes resulted in a low percentage of normal larvae with an EC50 value of 0.90 µM. This study shows that reproductive processes of ascidians are highly sensitive to xenobiotics suggesting that they may be considered a reliable biomarker and that ascidians are suitable model organisms to assess marine environmental quality.

Five-Year Incidence of Visual Impairment in Middle-Aged Iranians: The Shahroud Eye Cohort Study.

PubMed

Hashemi, Hassan; Mehravaran, Shiva; Emamian, Mohammad Hassan; Fotouhi, Akbar

2017-02-01

To study the 5-year incidence of visual impairment and its causes and risk factors, in the middle-aged Iranian sample of the Shahroud Eye Cohort Study (ShECS). Data from subjects who had participated in both phases of the ShECS were used to determine age- and sex-specific incidence rates of visual impairment using the World Health Organization (WHO) definitions for bilateral low vision (visual acuity, VA, >0.5 and ≤1.3 LogMAR in the better eye) and blindness (VA worse than 1.3 LogMAR in the better eye). Risk ratios (RR) and 95% confidence intervals (CIs) were calculated using multivariable log-binomial regression. Of the 5079 ShECS I survivors, 4737 (93.3%) completed the 5-year follow-up. Their mean age at baseline was 50.9 ± 6.2 years, and 58.9% were female. The incidence of visual impairment was 1.12% (95% CI 0.82-1.42%) by presenting VA and 0.19% (95% CI 0.07-0.32%) by best-corrected VA; leading causes of the former were uncorrected refractive error (81.3%) and diabetic retinopathy (15.1%). In the multivariable model, risk factors for incident visual impairment by presenting VA were older age (RR 1.05, p = 0.044), lower education (RR 0.89, p = 0.002), and diabetes (RR 3.74, p < 0.001). This is the first incidence study of visual impairment in a middle-aged Iranian population. Since age is a major risk factor, the number of visually impaired is expected to increase as the population ages, and less treatable causes such as diabetic retinopathy begin to surface. Measures for tackling uncorrected refractive error and enhancing diabetes screening and preventive programs are recommended.

Arylazolyl(azinyl)thioacetanilides: Part 19: Discovery of Novel Substituted Imidazo[4,5-b]pyridin-2-ylthioacetanilides as Potent HIV NNRTIs Via a Structure-based Bioisosterism Approach.

PubMed

Li, Xiao; Huang, Boshi; Zhou, Zhongxia; Gao, Ping; Pannecouque, Christophe; Daelemans, Dirk; De Clercq, Erik; Zhan, Peng; Liu, Xinyong

2016-08-01

With the continuation of our unremitting efforts toward the discovery of potent HIV-1 NNRTIs, a series of novel imidazo[4,5-b]pyridin-2-ylthioacetanilides were designed, synthesized, and evaluated for their antiviral activities through combining bioisosteric replacement and structure-based drug design. Almost all of the title compounds displayed moderate to good activities against wild-type (wt) HIV-1 strain with EC50 values ranging from 0.059 to 1.41 μm in a cell-based antiviral assay. Thereinto, compounds 12 and 13 were the most active two analogues possessing an EC50 value of 0.059 and 0.073 μm against wt HIV-1, respectively, which was much more effective than the control drug nevirapine (EC50 = 0.26 μm) and comparable to delavirdine (EC50 = 0.038 μm). In addition, one selected compound showed a remarkable reverse transcriptase inhibitory activity compared to nevirapine and etravirine. In the end of this manuscript, preliminary structure-activity relationships (SARs) and molecular modeling studies were detailedly discussed, which may provide valuable insights for further optimization. © 2016 The Authors. Chemical Biology & Drug Design Published by John Wiley & Sons A/S.

Dissolved organic carbon reduces the toxicity of copper to germlings of the macroalgae, Fucus vesiculosus.

PubMed

Brooks, Steven J; Bolam, Thi; Tolhurst, Laura; Bassett, Janice; La Roche, Jay; Waldock, Mike; Barry, Jon; Thomas, Kevin V

2008-05-01

This study investigates the effects of waterborne copper exposure on germling growth in chemically defined seawater. Germlings of the macroalgae, Fucus vesiculosus were exposed to a range of copper and dissolved organic carbon (DOC as humic acid) concentrations over 14 days. Germling growth was found to be a sensitive indicator of copper exposure with total copper (TCu) and labile copper (LCu) EC(50) values of approximately 40 and 20 microg/L, respectively, in the absence of added DOC. The addition of DOC into the exposure media provided germlings with protection against copper toxicity, with an increased TCu EC(50) value of 117.3 microg/L at a corrected DOC (cDOC from humic acid only) concentration of 2.03 mg/L. The LCu EC(50) was not affected by a cDOC concentration of 1.65 mg/L or less, suggesting that the LCu concentration not the TCu concentration was responsible for inhibiting germling growth. However, at a cDOC concentration of approximately 2mg/L an increase in the LCu EC(50) suggests that the LCu concentration may play a role in the overall toxicity to the germlings. This is contrary to current understanding of aquatic copper toxicity and possible explanations for this are discussed.

Automated swimming activity monitor for examining temporal patterns of toxicant effects on individual Daphnia magna.

PubMed

Bahrndorff, Simon; Michaelsen, Thomas Yssing; Jensen, Anne; Marcussen, Laurits Faarup; Nielsen, Majken Elley; Roslev, Peter

2016-07-01

Aquatic pollutants are often biologically active at low concentrations and impact on biota in combination with other abiotic stressors. Traditional toxicity tests may not detect these effects, and there is a need for sensitive high-throughput methods for detecting sublethal effects. We have evaluated an automated infra-red (IR) light-based monitor for recording the swimming activity of Daphnia magna to establish temporal patterns of toxicant effects on an individual level. Activity was recorded for 48 h and the sensitivity of the monitor was evaluated by exposing D. magna to the reference chemicals K2 Cr2 O7 at 15, 20 and 25 °C and 2,4-dichlorophenol at 20 °C. Significant effects (P < 0.001) of toxicant concentrations, exposure time and incubation temperatures were observed. At 15 °C, the swimming activity remained unchanged for 48 h at sublethal concentrations of K2 Cr2 O7 whereas activity at 20 and 25 °C was more biphasic with decreases in activity occurring after 12-18 h. A similar biphasic pattern was observed after 2,4-dichlorophenol exposure at 20 °C. EC50 values for 2,4-dichlorophenol and K2 Cr2 O7 determined from automated recording of swimming activity showed increasing toxicity with time corresponding to decreases in EC50 of 0.03-0.07 mg l(-1) h(-1) . EC50 values determined after 48 h were comparable or lower than EC50 values based on visual inspection according to ISO 6341. The results demonstrated that the swimming activity monitor is capable of detecting sublethal behavioural effects that are toxicant and temperature dependent. The method allows EC values to be established at different time points and can serve as a high-throughput screening tool in toxicity testing. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Acute, sublethal and combination effects of azadirachtin and Bacillus thuringiensis toxins on Helicoverpa armigera (Lepidoptera: Noctuidae) larvae.

PubMed

Singh, G; Rup, P J; Koul, Opender

2007-08-01

The efficacy of neem (1500 ppm azadirachtin (AI)), Delfin WG, a biological insecticide based on selected strain of Bacillus thuringiensis Berliner (Bt) subspecies kurstaki, and Cry1Ac protein, either individually or in combination, were examined against first to fourth instar Helicoverpa armigera (Hübner) larvae. Using an oral administration method, various growth inhibitory concentrations (EC) and lethal concentrations (LC) were determined for each bioagent. Combinations of sublethal concentrations of Bt spray formulation with azadirachtin at EC50 or EC95 levels not only enhanced the toxicity, but also reduced the duration of action when used in a mixture. The LC20 and LC50 values for Cry1Ac toxin were 0.06 and 0.22 microg ml-1, respectively. Bt-azadirachtin combinations of LC50+EC20 and LC50+EC50 result in 100% mortality. The mortality also was significant in LC20+EC20 and LC20+EC50 mixtures. These studies imply that the combined action is not synergistic but complimentary, with azadirachtin particularly facilitating the action of Bt. The Bt spray-azadirachtin combination is more economical than combinations that involve isolating the toxic protein, as the Bt spray formulations can be combined in a spray mixture with neem. These combinations may be useful for controlling bollworm populations that have acquired resistance to Bt as they may not survive the effect of mixture. Azadirachtin may be useful as a means of reducing the endotoxin concentrations in a mixture, to promote increased economic savings and further reduce the probability of resistance development to either insect control agent.

Personalized Medicine in Veterans with Traumatic Brain Injuries

DTIC Science & Technology

2012-05-01

UPGMA ) based on cosine correlation of row mean centered log2 signal values; this was the top 50%-tile, 3) In the DA top 50%-tile, selected probe sets...GeneMaths XT following row mean centering of log2 trans- formed MAS5.0 signal values; probe set cluster- ing was performed by the UPGMA method using...hierarchical clustering analysis using the UPGMA algorithm with cosine correlation as the similarity metric. Results are presented as a heat map (left

Synthesis and antioxidant evaluation of (S,S)- and (R,R)-secoisolariciresinol diglucosides (SDGs)

PubMed Central

Mishra, Om P.; Simmons, Nicholas; Tyagi, Sonia; Pietrofesa, Ralph; Shuvaev, Vladimir V.; Valiulin, Roman A.; Heretsch, Philipp; Nicolaou, K. C.; Christofidou-Solomidou, Melpo

2013-01-01

Secoisolariciresinol diglucosides (SDGs) (S,S)-SDG-1 (major isomer in flaxseed) and (R,R)-SDG-2 (minor isomer in flaxseed) were synthesized from vanillin via secoisolariciresinol (6) and glucosyl donor 7 through a concise route that involved chromatographic separation of diastereomeric diglucoside derivatives (S,S)-8 and (R,R)-9. Synthetic (S,S)-SDG-1 and (R,R)-SDG-2 exhibited potent antioxidant properties (EC50 = 292.17 ± 27.71 μM and 331.94 ± 21.21 μM, respectively) which compared well with that of natural (S,S)-SDG-1 (EC50 = 275.24 ± 13.15 μM). These values are significantly lower than those of ascorbic acid (EC50 = 1129.32 ± 88.79 μM) and α-tocopherol (EC50 = 944.62 ± 148.00 μM). Compounds (S,S)-SDG-1 and (R,R)-SDG-2 also demonstrated powerful scavenging activities against hydroxyl [natural (S,S)-SDG-1: 3.68 ± 0.27; synthetic (S,S)-SDG-1: 2.09 ± 0.16; synthetic (R,R)-SDG-2: 1.96 ± 0.27], peroxyl [natural (S,S)-SDG-1: 2.55 ± 0.11; synthetic (S,S)-SDG-1: 2.20 ± 0.10; synthetic (R,R)-SDG-2: 3.03 ± 0.04] and DPPH [natural (S,S)-SDG-1: EC50 = 83.94 ± 2.80 μM; synthetic (S,S)-SDG-1: EC50 = 157.54 ± 21.30; synthetic (R,R)-SDG-2: EC50 = 123.63 ± 8.67] radicals. These results confirm previous studies with naturally occurring (S,S)-SDG-1 and establish both (S,S)-SDG-1 and (R,R)-SDG-2 as potent antioxidants and free radical scavengers for potential in vivo use. PMID:23978651

Selectivity and activity of adenine dinucleotides at recombinant P2X2 and P2Y1 purinoceptors.

PubMed Central

Pintor, J.; King, B. F.; Miras-Portugal, M. T.; Burnstock, G.

1996-01-01

1. Adenine dinucleotides (Ap3A, x = 2-6) are naturally-occurring polyphosphated nucleotidic substances which are found in the CNS and are known to be released in a calcium-dependent manner from storage vesicles in brain synaptosomes. The selectivity and activity of adenine dinucleotides for neuronally-derived recombinant P2 purinoceptors were studied using P2X2 and P2Y1 subtypes expressed in Xenopus oocytes. 2. For the P2Y1 subtype derived from chick brain, Ap3A was equipotent and as active as ATP (EC50 values: 375 +/- 86 nM and 334 +/- 25 nM, respectively). Ap4A was a weak partial agonist and other dinucleotides were inactive as agonists. None of the inactive dinucleotides were antagonists nor modulated the activity of Ap3A and ATP. 3. For the P2X2 subtype derived from rat PC12 cells, Ap4A was as active as ATP but less potent (EC50 values: 15.2 +/- 1 microM and 3.7 +/- 0.7 microM, respectively). Other adenosine dinucleotides were inactive as either agonists or antagonists. 4. Ap5A (1-100 nM) potentiated ATP-responses at the P2X2 subtype, showing an EC50 of 2.95 +/- 0.7 nM for this modulatory effect. Ap5A (10 nM) shifted the concentration-response curves for ATP to the left by one-half log10 unit but did not alter the Hill co-efficient for ATP (nH = 2.1 +/- 0.1). Ap5A (10 nM) failed to potentiate Ap4A-responses but did enhance the efficacy of the P2 purinoceptor antagonist, suramin, by 12 fold at the P2X2 subtype. 5. In conclusion, the results show that ionotropic (P2X2) and metabotropic (P2Y1) ATP receptors which occur in the CNS are activated selectively by naturally-occurring adenine dinucleotides which are known to be released with nucleotides from storage vesicles. The observed potentiation of P2X2-responses by Ap5A, where co-released with ATP by brain synaptosomes, may have a functional bearing in purinergic signalling in the CNS. PMID:8922753

Comparison of laboratory single species and field population-level effects of the pyrethroid insecticide lambda-cyhalothrin on freshwater invertebrates.

PubMed

Schroer, A F W; Belgers, J D M; Brock, T C M; Matser, A M; Maund, S J; Van den Brink, P J

2004-04-01

The toxicity of the pyrethroid insecticide lambda-cyhalothrin to freshwater invertebrates has been investigated using data from short-term laboratory toxicity tests and in situ bioassays and population-level effects in field microcosms. In laboratory tests, patterns of toxicity were consistent with previous data on pyrethroids. The midge Chaoborus obscuripes was most sensitive (48- and 96-h EC50 = 2.8 ng/L). Other insect larvae (Hemiptera, Ephemeroptera) and macrocrustacea (Amphipoda, Isopoda) were also relatively sensitive, with 48- and 96-h EC50 values between 10 and 100 ng/L. Generally, microcrustacea (Cladocera, Copepoda) and larvae of certain insect groups (Odonata and Chironomidae) were less sensitive, with 48-h EC50 values higher than 100 ng/L. Mollusca and Plathelminthes were insensitive and were unaffected at concentrations at and above the water solubility (5 microg/L). Generally, the EC50 values based on initial population responses in field enclosures were similar to values derived from laboratory tests with the same taxa. Also, the corresponding fifth and tenth percentile hazard concentrations (HC5 and HC10) were similar (laboratory HC5 = 2.7 ng/L and field HC5 = 4.1 ng/L; laboratory and field HC10 = 5.1 ng/L), at least when based on the same sensitive taxonomic groups (insects and crustaceans) and when a similar concentration range was taken into account. In the three field enclosure experiments and at a treatment level of 10 ng/L, consistent effects were observed for only one population (Chaoborus obscuripes), with recovery taking place within 3 to 6 weeks. The laboratory HC5 (2.7 ng/L) and HC10 (5.1 ng/L) based on acute EC50 values of all aquatic arthropod taxa were both lower than this 10 ng/L, a concentration that might represent the "regulatory acceptable concentration." The HC5 and HC10 values in this study in The Netherlands (based on static laboratory tests with freshwater arthropods) were very similar to those derived from a previous study in the United Kingdom (1.4 and 3.3 ng/L). This suggests that for pesticides like lambda-cyhalothrin, HC5 values based on static laboratory tests may provide a conservative estimate of the potential for community-level effects under field conditions. While these HC5 values are conservative for initial effects, they do not provide information on recovery potential, which may be important for regulatory decision-making.

Further investigation into the signal transduction mechanism of the 5-HT4-like receptor in the circular smooth muscle of human colon.

PubMed Central

McLean, P. G.; Coupar, I. M.

1996-01-01

1. The nature of the receptor coupling mechanism of the 5-hydroxytryptamine4 (5-HT4) receptor in the circular smooth muscle of the human colon has been further investigated. 2. 5-HT stimulated cyclic AMP generation and caused a relaxation in a concentration-dependent fashion, with EC50 values of 175.5 and 274.9 nM respectively. DAU 6236 increased cyclic AMP formation and caused a relaxant effect but was a partial agonist relative to 5-HT. 3. The 5-HT4 receptor antagonist, GR 113808, inhibited cyclic AMP formation and relaxation induced by 5-HT with -log Ki values of 9.1 (cyclic AMP) and 8.9 (relaxation) and apparent pA2 values of 9.2 (cyclic AMP) and 9.5 (relaxation). 4. Ondansetron and methysergide failed to inhibit cyclic AMP formation or the relaxation induced by 5-HT. 5. The phosphodiesterase inhibitor, IBMX, produced a concentration-dependent relaxation (EC50 = 30 microM) and at 1 microM it enhanced the 5-HT-induced relaxation producing a leftward shift of the 5-HT concentration-effect curve with a concentration-ratio of 4.1. Rolipram caused a concentration-dependent relaxation (EC50 = 564.8 nM) and at 200 nm caused a leftward shift of the concentration-effect curve to 5-HT with a concentration-ratio of 5.5. 6. Application of the adenylyl cyclase inhibitor, SQ 22536 (0.1 mM), and the protein kinase inhibitors, H7 (100 nM) and H89 (200 nM), inhibited the relaxant effect of 5-HT inducing a rightward shift of the concentration-effect curve with concentration-ratios of 10.1, 2.7 and 4.2 respectively. 7. Forskolin stimulated cyclic AMP production and caused a relaxation. The maximum relaxant effect of forskolin (6 microM, 13.8 +/- 1.9 cm.s) was not significantly different from the maximum relaxant effect of 5-HT (10 microM, 12.7 +/- 4.9 cm.s). However, the cyclic AMP levels stimulated by forskolin (6 microM, 49.3 +/- 6.6 pmol mg-1) were markedly greater than those stimulated by 5-HT (10 microM, 7.6 +/- 2.0 pmol mg-1). 8. In conclusion, these results indicate that the 5-HT4 receptors of the circular smooth muscle of human colon mediate relaxation and inhibition of spontaneous contractions via activation of adenylyl cyclase, formation of cyclic AMP and activation of protein kinase A. PMID:8799582

Further investigation into the signal transduction mechanism of the 5-HT4-like receptor in the circular smooth muscle of human colon.

PubMed

McLean, P G; Coupar, I M

1996-06-01

1. The nature of the receptor coupling mechanism of the 5-hydroxytryptamine4 (5-HT4) receptor in the circular smooth muscle of the human colon has been further investigated. 2. 5-HT stimulated cyclic AMP generation and caused a relaxation in a concentration-dependent fashion, with EC50 values of 175.5 and 274.9 nM respectively. DAU 6236 increased cyclic AMP formation and caused a relaxant effect but was a partial agonist relative to 5-HT. 3. The 5-HT4 receptor antagonist, GR 113808, inhibited cyclic AMP formation and relaxation induced by 5-HT with -log Ki values of 9.1 (cyclic AMP) and 8.9 (relaxation) and apparent pA2 values of 9.2 (cyclic AMP) and 9.5 (relaxation). 4. Ondansetron and methysergide failed to inhibit cyclic AMP formation or the relaxation induced by 5-HT. 5. The phosphodiesterase inhibitor, IBMX, produced a concentration-dependent relaxation (EC50 = 30 microM) and at 1 microM it enhanced the 5-HT-induced relaxation producing a leftward shift of the 5-HT concentration-effect curve with a concentration-ratio of 4.1. Rolipram caused a concentration-dependent relaxation (EC50 = 564.8 nM) and at 200 nm caused a leftward shift of the concentration-effect curve to 5-HT with a concentration-ratio of 5.5. 6. Application of the adenylyl cyclase inhibitor, SQ 22536 (0.1 mM), and the protein kinase inhibitors, H7 (100 nM) and H89 (200 nM), inhibited the relaxant effect of 5-HT inducing a rightward shift of the concentration-effect curve with concentration-ratios of 10.1, 2.7 and 4.2 respectively. 7. Forskolin stimulated cyclic AMP production and caused a relaxation. The maximum relaxant effect of forskolin (6 microM, 13.8 +/- 1.9 cm.s) was not significantly different from the maximum relaxant effect of 5-HT (10 microM, 12.7 +/- 4.9 cm.s). However, the cyclic AMP levels stimulated by forskolin (6 microM, 49.3 +/- 6.6 pmol mg-1) were markedly greater than those stimulated by 5-HT (10 microM, 7.6 +/- 2.0 pmol mg-1). 8. In conclusion, these results indicate that the 5-HT4 receptors of the circular smooth muscle of human colon mediate relaxation and inhibition of spontaneous contractions via activation of adenylyl cyclase, formation of cyclic AMP and activation of protein kinase A.

Advances on the determination of thresholds of Cu phytotoxicity in field-contaminated soils in central Chile.

PubMed

Mondaca, Pedro; Catrin, Joanie; Verdejo, José; Sauvé, Sébastien; Neaman, Alexander

2017-04-01

To better determine phytotoxicity thresholds for metals in the soil, studies should use actual field-contaminated soil samples rather than metal-spiked soil preparations. However, there are surprisingly few such data available for Cu phytotoxicity in field-contaminated soils. Moreover, these studies differ from each other with regards to soil characteristics and experimental setups. This study aimed at more accurately estimating Cu phytotoxicity thresholds using field-collected agricultural soils (Entisols) from areas exposed to contamination from Cu mining. For this purpose, the exposure to Cu was assessed by measuring total soil Cu, soluble Cu, free Cu 2+ activity, and Cu in the plant aerial tissues. On the other hand, two bioassay durations (short-term and long-term), three plant species (Avena sativa L., Brassica rapa CrGC syn. Rbr, and Lolium perenne L.), and five biometric endpoints (shoot length and weight, root length and weight, and number of seed pods) were considered. Overall plant growth was best predicted by total Cu content of the soil. Despite some confounding factors, it was possible to determine EC 10 , EC 25 and EC 50 of total Cu in the soil. Brassica rapa was more sensitive than Avena sativa for all endpoints, while Lolium perenne was of intermediate sensitivity. For the short-term bioassay (21 days for all three species), the averaged EC 10 , EC 25 and EC 50 values of total soil Cu (in mg kg -1 ) were 356, 621, and 904, respectively. For the long-term bioassay (62 days for oat and 42 days for turnip), the averaged EC 10 , EC 25 and EC 50 values of total soil Cu (in mg kg -1 ) were 355, 513, and 688, respectively. The obtained results indicate that chronic test is a suitable method for assessing Cu phytotoxicity in field-contaminated soils. Copyright © 2017 Elsevier Ltd. All rights reserved.

Trialkylamine Derivatives Containing a Triazole Moiety as Promising Ergosterol Biosynthesis Inhibitor: Design, Synthesis, and Antifungal Activity.

PubMed

Sui, Guoqing; Zhang, Wen; Zhou, Kun; Li, Yulin; Zhang, Bingyu; Xu, Dan; Zou, Yong; Zhou, Wenming

2017-01-01

As a part of our continuing research on amine derivative antifungal agents, 19 novel target compounds containing 1,2,4-triazole and tertiary amine moieties were designed and synthesized, and their in vitro antifungal activities against six phytopathogenic fungi (Magnaporthe grisea, Alternaria solani, Fusarium solani, Curvularia lunata, A. alternata, F. graminearum) were assayed. All target compounds were elucidated by means of 1 H-NMR, 13 C-NMR, high resolution (HR)-MS, and IR analysis. The results showed that most of the derivatives exhibited obvious activity against each of the fungi at 50 µg/mL. Among them, compounds 7f, l, and o displayed excellent activity against A. solani with median effective concentration values (EC 50 ) of 2.88, 8.20, and 1.92 µg/mL. 7o in particular was superior to tebuconazole (EC 50 =2.03 µg/mL), a commercial fungicide. Furthermore, compounds 7j, k, and m also showed good activity against F. graminearum with EC 50 values of 11.60, 5.14, and 16.24 µg/mL, and the value of 7k was extremely close to that of tebuconazole (EC 50 =3.13 µg/mL). The preliminary analysis of the structure-activity relationship (SAR) demonstrated that combination of the active structure of 1,2,4-triazole with the tertiary amine group containing benzene rings effectively increased the antifungal activities. Generally, introducing halogen atoms obviously improved activities against most of the test fungi to varying degrees, while the presence of OMe decreased the activities. Thus, the results strongly indicate that the newly synthesized derivatives should be lead compounds for the development of novel antifungal agents for the effective control of phytopathogenic fungi.

A chronic toxicity test for the tropical marine snail Nassarius dorsatus to assess the toxicity of copper, aluminium, gallium, and molybdenum.

PubMed

Trenfield, Melanie A; van Dam, Joost W; Harford, Andrew J; Parry, David; Streten, Claire; Gibb, Karen; van Dam, Rick A

2016-07-01

Chronic toxicity test methods for assessing the toxicity of contaminants to tropical marine organisms are generally lacking. A 96-h chronic growth rate toxicity test was developed for the larval stage of the tropical dogwhelk, Nassarius dorsatus. Growth rates of N. dorsatus larvae were assessed following exposures to copper (Cu), aluminium (Al), gallium (Ga), and molybdenum (Mo). Exposure to Cu at 28 °C validated the sensitivity of the test method, with 10% (EC10) and 50% (EC50) effect concentrations of 4.2 μg/L and 7.3 μg/L Cu, respectively. The EC10 and EC50 values for Al (<0.45-μm filtered fraction) at 28 °C were 115 μg/L and 185 μg/L, respectively. The toxicity of Cu and Al was also assessed at 24 °C and 31 °C, representing average year-round water temperatures for subtropical and tropical Australian coastal environments. At 24 °C, the growth rate of control larvae was reduced by 52% compared with the growth rate at 28 °C and there was an increase in sensitivity to Cu (EC50 = 4.7 μg/L) but a similar sensitivity to Al (EC50 = 180 μg/L). At 31 °C the control growth rate increased by 35% from that measured at 28 °C and there was reduced sensitivity to both Cu and Al (EC50s = 8.5 μg/L and 642 μg/L, respectively). There was minimal toxicity resulting from Ga (EC50 = 4560 μg/L) and Mo (no effect at ≤7000 μg/L Mo). Environ Toxicol Chem 2016;35:1788-1795. © 2015 SETAC. © 2015 SETAC.

PHOTOINDUCED TOXICITY OF PAHS AND ALKYLATED PAHS TO A MARINE INFAUNAL AMPHIPOD (RHEPOXYNIUS ABRONIUS)

EPA Science Inventory

The marine infaunal amphipod Rhepoxynius abronius was exposed in standard 10-day toxicity tests to sediments contaminated with parent or alkylated PAHs. After exposures, mortalities (LC50 values) and the ability to rebury in control sediment (EC50 values) were determined. Survivo...

Adamantyl- and other polycyclic cage-based conjugates of desferrioxamine B (DFOB) for treating iron-mediated toxicity in cell models of Parkinson's disease.

PubMed

Telfer, Thomas J; Liddell, Jeffrey R; Duncan, Clare; White, Anthony R; Codd, Rachel

2017-04-15

The death of dopaminergic neurons is a major pathological hallmark of Parkinson's disease (PD). Elevated iron within the substantia nigra of the PD brain is thought to catalyze this neuronal death through hydroxyl radical-derived oxidative damage. Removing this excess iron presents a potential therapeutic strategy for PD. Seventeen derivatives of the non-toxic iron chelator desferrioxamine B (DFOB) were prepared by the conjugation of adamantyl- (1-4, 8-12), deconstructed adamantyl units (5-7), norborna(e)ne- (13-16) or bicyclo[2.2.2]octane-based (17) ancillary fragments to the terminal amine group. The range of experimental logP values of 1-17 (logP=0.15-2.82) was greater than water soluble DFOB (logP -2.29), with the increased hydrophobicity designed to improve cell membrane carriage to facilitate intracellular iron sequestration. The first activity screen showed compounds with methyl-substituted adamantyl (1-3), noradamantyl (5), or 1-pentylbicyclo[2.2.2]octane (17) ancillary groups significantly rescued iron-mediated oxidative stress in confluent PD-relevant SK-N-BE2-M17 neuroblastoma cells (M17 cells) exposed to 1,1'-dimethyl-4,4'-bipyridinium (paraquat, PQ) or H 2 O 2 . The second dose-dependence screen ranked 1-3 and 17 as the top candidates (EC 50 ∼10µM) in the rescue of PQ-treated M17 cells. The ancillary fragments of 1-3 and 17 clustered in a region defined by a close-to-zero dipole moment, logP values of 2-2.8 and a surface area:volume ratio of 0.60-0.61. Results of iron leaching studies indicate that the compounds may be operating via mechanisms beyond solely removing intracellular iron. The DFOB conjugates with methyl-substituted adamantyl ancillary groups (1-3) were the top and most consistent performers in this class of compound designed for PD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of fenoterol-induced constitutive beta(2)-adrenoceptor activity on contractile receptor function in airway smooth muscle.

PubMed

de Vries, B; Roffel, A F; Zaagsma, J; Meurs, H

2001-11-23

In the present study, we investigated the effect of fenoterol-induced constitutive beta(2)-adrenoceptor activity on muscarinic receptor agonist- and histamine-induced bovine tracheal smooth muscle contractions. Bovine tracheal smooth muscle strips were incubated with 10 microM fenoterol or vehicle for various periods of time (5, 30 min, 18 h) at 37 degrees C. After extensive washout (3 h, 37 degrees C), isometric contractions were measured to the full muscarinic receptor agonist methacholine, the partial muscarinic receptor agonist 4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium (McN-A-343) and histamine. Fenoterol treatment significantly reduced the sensitivity (pEC(50)) to methacholine in a time-dependent manner, without affecting maximal contraction (E(max)). Fenoterol treatment similarly reduced the pEC(50) of McN-A-343 and histamine; however, E(max) values were also reduced, to approximately 70% of control after 18-h treatment. The inverse agonist timolol, having no effect on control preparations, consistently restored the reduced pEC(50) and E(max) values of the contractile agonists. Remarkably, in the presence of timolol the pEC(50) values of McN-A-343 and histamine in fenoterol-treated airways were significantly enhanced compared to controls. In conclusion, fenoterol-induced constitutive beta(2)-adrenoceptor activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist timolol. Moreover, after beta(2)-adrenoceptor agonist treatment, inverse agonism by beta-adrenoceptor antagonists may cause enhanced airway reactivity to contractile mediators.

Influence of selected water quality characteristics on the toxicity of lambda-cyhalothrin and gamma-cyhalothrin to Hyalella azteca.

PubMed

Smith, S; Lizotte, R E

2007-11-01

This study was conducted to assess the influence of suspended solids, dissolved organic carbon, and phytoplankton (as chlorophyll a) water quality characteristics on lambda-cyhalothrin and gamma-cyhalothrin aqueous toxicity to Hyalella azteca using natural water from 12 ponds and lakes in Mississippi, USA with varying water quality characteristics. H. azteca 48-h immobilization EC50 values ranged from 1.4 to 15.7 ng/L and 0.6 to 13.4 ng/L for lambda-cyhalothrin and gamma-cyhalothrin, respectively. For both pyrethroids, EC50 values linearly increased as turbidity, suspended solids, dissolved organic carbon and chlorophyll a concentrations increased.

In Vitro Screening of Opiod Antagonist Effectiveness

DTIC Science & Technology

2018-04-01

with a co-administration of acrylfentanyl and naloxone. Reversibility of acrylfentanyl was achieved at naloxone concentrations comparable to those of...EC50, EC90, and efficacy values were calculated (Figure 4). These values were compared to those of fentanyl (Table 1). 1 2 3 4 5 6 7 8 9 10 11 12... compare that to the metabolic rate of the reversal agent, itself. Metabolic clearance data, when combined with a potency and competition assay

Efficacy of free and nanoencapsulated Eucalyptus citriodora essential oils on sheep gastrointestinal nematodes and toxicity for mice.

PubMed

Ribeiro, J C; Ribeiro, W L C; Camurça-Vasconcelos, A L F; Macedo, I T F; Santos, J M L; Paula, H C B; Araújo Filho, J V; Magalhães, R D; Bevilaqua, C M L

2014-08-29

Herbal medicines with anthelmintic effects are alternatives for the sustainable control and prevention of disease caused by gastrointestinal parasites. The nanoencapsulation of essential oils has been proposed to enhance the absorption of their constituents and improve their efficacy. The present study aimed to evaluate the efficacy of free and nanoencapsulated Eucalyptus citriodora essential oil (EcEO) on the control of gastrointestinal nematodes of small ruminants in vitro and in vivo. Chitosan was used as a matrix for the formulation of a nanoemulsion. Chromatographic and physico-chemical analyses of EcEO were performed. Egg hatch (EHT) and larval development (LDT) tests were conducted to evaluate the effectiveness of nanoencapsulated and free EcEO on the eggs and larvae of Haemonchus contortus. Acute toxicity of free and nanoencapsulated EcEO was evaluated using mice. Finally, nanoencapsulated EcEO efficacy on the control of gastrointestinal nematodes was calculated by fecal egg count reduction test (FECRT) treating 30 sheep naturally infected with 250 mg/kg of free and nanoencapsulated EcEO. In vitro tests were analyzed by an analysis of variance (ANOVA) followed by comparison with the Tukey test. The efficacy of FECRT was calculated by the BootStreet program through arithmetic average, using the formula 100 (1-XT/XC). To compare the differences between epg, the data were transformed to log(x+1) and subjected to an ANOVA to compare the significant differences between groups by Tukey's. The level of significance was P<0.05. The free (4 mg/ml concentration) and nanoencapsulated (2mg/ml concentration) EcEO inhibited larvae hatching by 97.2% and 92.8%, respectively. Free and nanoencapsulated EcEO at 8 mg/ml inhibited larval development by 99.8% and 98.1%, respectively. In the acute toxicity test, the LD10 and LD50 of free EcEO was 1999 and 2653 mg/kg, respectively, while the LD10 and LD50 of nanoencapsulated EcEO was 1121 and 1681 mg/kg, respectively. Nanoencapsulated and free EcEO reduced FEC similarly by 40.5% and 55.9%, respectively at 10 days post-treatment. Nanoencapsulated EcEO did not obtain the expected efficacy in vivo. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparative sensitivity of the cnidarian Exaiptasia pallida and a standard toxicity test suite: testing whole effluents intended for ocean disposal.

PubMed

Howe, P L; Reichelt-Brushett, A J; Krassoi, R; Micevska, T

2015-09-01

The sea anemone Exaiptasia pallida (formally Aiptasia pulchella) has been identified as a valuable test species for tropical marine ecotoxicology. Here, the sensitivities of newly developed endpoints for E. pallida to two unidentified whole effluents were compared to a standard suite of temperate toxicity test species and endpoints that are commonly used in toxicological risk assessments for tropical marine environments. For whole effluent 1 (WE1), a 96-h lethal concentration 50 % (LC50) of 40 (95 % confidence intervals, 30-54) % v/v and a 12-day LC50 of 12 (9-15) % v/v were estimated for E. pallida, exhibiting a significantly higher sensitivity than standard sub-lethal endpoints in Allorchestes compressa (96-h effective concentration 50 % (EC50) of >100 % v/v for immobilisation) and Hormosira banksii (72-h EC50 of >100 % v/v for germination), and a similar sensitivity to Mytilus edulis galloprovincialis larval development with a 48-h LC50 of 29 (28-30) % v/v. Sub-lethal effects of whole effluent 2 (WE2) on E. pallida pedal lacerate development resulted in an 8-day EC50 of 7 (3-11) % v/v, demonstrating comparable sensitivity of this endpoint to standardised sub-lethal endpoints in H. banksii (72-h EC50 of 11 (10-11) % v/v for germination), M. edulis galloprovincialis (48-h EC50 for larval development of 12 (9-14) % v/v) and Heliocidaris tuberculata (1-h EC50 of 13 (12-14) % v/v for fertilisation; 72-h EC50 of 26 (25-27) % v/v for larval development) and a significantly higher sensitivity than A. compressa immobilisation (96-h EC50 of >100 % v/v). The sensitivity of E. pallida compared to a standard test species suite highlights the value in standardising the newly developed toxicity test methods for inclusion in routine toxicological risk assessment of complex whole effluents. Importantly, this species provides an additional taxonomic group to the test species that are currently available for tropical marine ecotoxicology and, being a cnidarian, may represent important tropical marine environments including coral reefs.

Optimization and field use of a bioassay to monitor sea lice Lepeophtheirus salmonis sensitivity to emamectin benzoate.

PubMed

Westcott, Jillian D; Stryhn, Henrik; Burka, John F; Hammell, K Larry

2008-04-01

A bioassay for sea lice Lepeophtheirus salmonis sensitivity towards emamectin benzoate (EMB) was validated for field use. A probit regression model with natural responsiveness was used for the number of affected (moribund or dead) sea lice in bioassays involving different concentrations of EMB. Bioassay optimization included an evaluation of the inter-rater reliability of sea lice responsiveness to EMB and an evaluation of gender-related differences in susceptibility. Adoption of a set of bioassay response criteria improved the concordance (evaluated using the concordance correlation coefficient) between raters' assessments and the model estimation of EC50 values (the 'effective concentration' leading to a response of 50% of the lice not prone to natural response). An evaluation of gender-related differences in EMB susceptibility indicated that preadult stage female sea lice exhibited a significantly larger sensitivity towards EMB in 12 of 19 bioassays compared to preadult males. In order to evaluate sea lice sensitivity to EMB in eastern Canada, the intensive salmon farming area in the Bay of Fundy in southwestern New Brunswick was divided into 4 distinct regions based on industry health management practices and hydrographics. A total of 38 bioassays were completed from 2002 to 2005 using populations of preadult stage sea lice collected from Atlantic salmon Salmo salar farms within the 4 described regions. There was no significant overall effect of region or year on EC50 values; however, analysis of variance indicated a significant effect of time of year on EC50 values in 2002 and a potential effect in 2004 to 2005. Although the range of EC50 values obtained in this 3 yr study did not appear sufficient to affect current clinical success in the control of sea lice, the results suggest a seasonal- or temperature-associated variation in sensitivity to EMB. This will need to be considered if changes in EMB efficacy occur in the future.

Evidence of adaptive tolerance to nickel in isolates of Cenococcum geophilum from serpentine soils.

PubMed

Gonçalves, Susana C; Martins-Loução, M Amélia; Freitas, Helena

2009-04-01

Selection for metal-tolerant ecotypes of ectomycorrhizal (ECM) fungi has been reported in instances of metal contamination of soils as a result of human activities. However, no study has yet provided evidence that natural metalliferous soils, such as serpentine soils, can drive the evolution of metal tolerance in ECM fungi. We examined in vitro Ni tolerance in isolates of Cenococcum geophilum from serpentine and non-serpentine soils to assess whether isolates from serpentine soils exhibited patterns consistent with adaptation to elevated levels of Ni, a typical feature of serpentine. A second objective was to investigate the relationship between Ni tolerance and specific growth rates (micro) among isolates to increase our understanding of possible tolerance/growth trade-offs. Isolates from both soil types were screened for Ni tolerance by measuring biomass production in liquid media with increasing Ni concentrations, so that the effective concentration of Ni inhibiting fungal growth by 50% (EC(50)) could be determined. Isolates of C. geophilum from serpentine soils exhibited significantly higher tolerance to Ni than non-serpentine isolates. The mean Ni EC(50) value for serpentine isolates (23.4 microg ml(-1)) was approximately seven times higher than the estimated value for non-serpentine isolates (3.38 microg ml(-1)). Although there was still a considerable variation in Ni sensitivity among the isolates, none of the serpentine isolates had EC(50) values for Ni within the range found for non-serpentine isolates. We found a negative correlation between EC(50) and micro values among isolates (r = -0.555). This trend, albeit only marginally significant (P = 0.06), indicates a potential trade-off between tolerance and growth, in agreement with selection against Ni tolerance in "normal" habitats. Overall, these results suggest that Ni tolerance arose among serpentine isolates of C. geophilum as an adaptive response to Ni exposure in serpentine soils.

Effect of soil organic matter content and pH on the toxicity of ZnO nanoparticles to Folsomia candida.

PubMed

Waalewijn-Kool, Pauline L; Rupp, Svenja; Lofts, Stephen; Svendsen, Claus; van Gestel, Cornelis A M

2014-10-01

Organic matter (OM) and pH may influence nanoparticle fate and effects in soil. This study investigated the influence of soil organic matter content and pH on the toxicity of ZnO-NP and ZnCl2 to Folsomia candida in four natural soils, having between 2.37% and 14.7% OM and [Formula: see text] levels between 5.0 and 6.8. Porewater Zn concentrations were much lower in ZnO-NP than in ZnCl2 spiked soils, resulting in higher Freundlich sorption constants for ZnO-NP. For ZnCl2 the porewater Zn concentrations were significantly higher in less organic soils, while for ZnO-NP the highest soluble Zn level (23mgZn/l) was measured in the most organic soil, which had the lowest pH. Free Zn(2+) ion concentrations were higher for ZnCl2 than for ZnO-NP and were greatly dependent on pH (pHpw) and dissolved organic carbon content of the pore water. The 28-d EC50 values for the effect of ZnCl2 on the reproduction of F. candida increased with increasing OM content from 356 to 1592mgZn/kg d.w. For ZnO-NP no correlation between EC50 values and OM content was found and EC50 values ranged from 1695 in the most organic soil to 4446mgZn/kg d.w. in the higher pH soil. When based on porewater and free Zn(2+) concentrations, EC50 values were higher for ZnCl2 than for ZnO-NP, and consistently decreased with increasing pHpw. This study shows that ZnO-NP toxicity is dependent on soil properties, but is mainly driven by soil pH. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of Neem (Azadirachta indica) on the Survival of Escherichia coli O157:H7 in Dairy Manure

PubMed Central

Ravva, Subbarao V.; Korn, Anna

2015-01-01

Escherichia coli O157:H7 (EcO157) shed in cattle manure can survive for extended periods of time and intervention strategies to control this pathogen at the source are critical as produce crops are often grown in proximity to animal raising operations. This study evaluated whether neem (Azadirachta indica), known for its antimicrobial and insecticidal properties, can be used to amend manure to control EcO157. The influence of neem materials (leaf, bark, and oil) on the survival of an apple juice outbreak strain of EcO157 in dairy manure was monitored. Neem leaf and bark supplements eliminated the pathogen in less than 10 d with a D-value (days for 90% elimination) of 1.3 d. In contrast, nearly 4 log CFU EcO157/g remained after 10 d in neem-free manure control. The ethyl acetate extractable fraction of neem leaves was inhibitory to the growth of EcO157 in LB broth. Azadirachtin, a neem product with insect antifeedant properties, failed to inhibit EcO157. Application of inexpensive neem supplements to control pathogens in manure and possibly in produce fields may be an option for controlling the transfer of foodborne pathogens from farm to fork. PMID:26184255

Effect of Neem (Azadirachta indica) on the Survival of Escherichia coli O157:H7 in Dairy Manure.

PubMed

Ravva, Subbarao V; Korn, Anna

2015-07-10

Escherichia coli O157:H7 (EcO157) shed in cattle manure can survive for extended periods of time and intervention strategies to control this pathogen at the source are critical as produce crops are often grown in proximity to animal raising operations. This study evaluated whether neem (Azadirachta indica), known for its antimicrobial and insecticidal properties, can be used to amend manure to control EcO157. The influence of neem materials (leaf, bark, and oil) on the survival of an apple juice outbreak strain of EcO157 in dairy manure was monitored. Neem leaf and bark supplements eliminated the pathogen in less than 10 d with a D-value (days for 90% elimination) of 1.3 d. In contrast, nearly 4 log CFU EcO157/g remained after 10 d in neem-free manure control. The ethyl acetate extractable fraction of neem leaves was inhibitory to the growth of EcO157 in LB broth. Azadirachtin, a neem product with insect antifeedant properties, failed to inhibit EcO157. Application of inexpensive neem supplements to control pathogens in manure and possibly in produce fields may be an option for controlling the transfer of foodborne pathogens from farm to fork.

High-resolution characterization of chemical heterogeneity in an alluvial aquifer

USGS Publications Warehouse

Schulmeister, M.K.; Healey, J.M.; McCall, G.W.; Birk, S.; Butler, J.J.

2002-01-01

The high-resolution capabilities of direct-push technology were exploited to develop new insights into the hydrochemistry at the margin of an alluvial aquifer. Hydrostratigraphic controls on groundwater flow and contaminant loading were revealed through the combined use of direct-push electrical conductivity (EC) logging and geochemical profiling. Vertical and lateral variations in groundwater chemistry were consistent with sedimentary features indicated by EC logs, and supported a conceptual model of recharge along the floodplain margin.

Functional toxicity and tolerance patterns of bioavailable Pd(II), Pt(II), and Rh(III) on suspended Saccharomyces cerevisiae cells assayed in tandem by a respirometric biosensor.

PubMed

Frazzoli, Chiara; Dragone, Roberto; Mantovani, Alberto; Massimi, Cristiana; Campanella, Luigi

2007-12-01

Toxicological implications of exposure to bioavailable platinum group metals, here Pd, Pt, and Rh, are still to be clarified. This study obtained by a biosensor-based method preliminary information on potential effects on cellular metabolism as well as on possible tolerance mechanisms. Aerobic respiration was taken as the toxicological end point to perform tandem tests, namely functional toxicity test and tolerance test. Cells were suspended in the absence of essential constituents for growth. The dose-response curves obtained by exposure (2 h) to the metals (nanogram per gram range) suggested the same mechanisms of action, with Rh showing the greatest curve steepness and the lowest EC50 value. Conservative (95% lower confidence interval) EC10 values were 187, 85 and 51 ng g(-1) for Pt, Pd, and Rh respectively. Tolerance patterns were tested during the same runs. The full tolerance obtained after 12 h of exposure to each metal suggested mitochondrial inhibition of aerobic respiration as a target effect. The hazard rating of the metals in the tolerance test changed in the Rh EC50 range, where Rh showed the lowest toxicity. The observed tolerance might suggest a protective mechanism such as metallothionein induction at concentrations around the EC50 values. The performance of the bioassay was satisfactory, in terms of the limit of detection, repeatability, reproducibility, roboustness, sensibility, and stability; the method's critical uncertainty sources were identified for improvements.

The differential time courses of the vasodilator effects of various 1,4-dihydropyridines in isolated human small arteries are correlated to their lipophilicity.

PubMed

van der Lee, R; Pfaffendorf, M; van Zwieten, P A

2000-11-01

To investigate a possible relationship between the time courses of action of various calcium antagonists and their lipophilicity, characterized as log P-values. The functional experiments were performed in vitro in human small subcutaneous arteries (internal diameter 591 +/- 51 microm, n = 7 for each concentration), obtained from cosmetic surgery (mamma reduction and abdominoplasty). The vessels were investigated in an isometric wire myograph. The vasodilator effect of the calcium antagonists was quantified by means of log IC50-values, and the onset of the vasodilator effect for each concentration studied was expressed as time to Eeq90-values (time to reach 90% of the maximal effect). Log IC50-values were -8.46 +/- 0.09, -8.33 +/- 0.25 and -8.72 +/- 0.16 for nifedipine, felodipine and (S)-lercanidipine, respectively (not significant). On average, nifedipine reached time to Eeq90 in 11 +/- 1 min. For felodipine and (S)-lercanidipine the corresponding values were 60 +/- 11 min and 99 +/- 9 min, respectively. The differences between these values were statistically significant (P< 0.01). In spite of these differences in the in-vitro human vascular model, the three calcium antagonists are equipotent with regard to their vasodilator effects. Linear regression analysis of the correlation between the logarithm of the membrane partition coefficient (log P-values) of the calcium antagonists tested [2.50, 4.46 and 6.88 for nifedipine, felodipine and (S)-lercanidipine, respectively] and their respective values found for time to Eeq90 was highly significant. It appears that a higher log P-value is correlated with a slower onset of action.

Evaluation of relative potencies for in vitro transactivation of the baikal seal aryl hydrocarbon receptor by dioxin-like compounds.

PubMed

Kim, Eun-Young; Suda, Tomoko; Tanabe, Shinsuke; Batoev, Valeriy B; Petrov, Evgeny A; Iwata, Hisato

2011-02-15

To evaluate the sensitivity and responses to dioxins and related compounds (DRCs) via aryl hydrocarbon receptor (AHR) in Baikal seals (Pusa sibirica), we constructed an in vitro reporter gene assay system. Baikal seal AHR (BS AHR) expression plasmid and a reporter plasmid containing CYP1A1 promoter were transfected in COS-7 cells. The cells were treated with six representative congeners, and dose-dependent responses were obtained for all the congeners. EC50 values of 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD, 2,3,7,8-TCDF, 2,3,4,7,8-PeCDF, and PCB126 were found to be 0.021, 1.8, 0.16, 2.4, and 2.5 nM, respectively. As the response did not reach the maximal plateau, EC50 value for PCB118 could not be obtained. The TCDD-EC50 for BS AHR was as high as that for dioxin sensitive C57BL/6 mouse AHR. The in vitro dose responses were further analyzed following an established systematic framework and multiple (20, 50, and 80%) relative potencies (REPs) to the maximum TCDD response. The estimates revealed lower REP ranges (20-80%) of PeCDD and PeCDF for BS AHR than for mouse AHR. Average of the 20, 50, and 80% REPs was designated as Baikal seal specific TCDD induction equivalency factor (BS IEF). The BS IEFs of PeCDD, TCDF, PeCDF, PCB126, and PCB118 were estimated as 0.010, 0.018, 0.0078, 0.0059, and 0.00010, respectively. Total TCDD induction equivalents (IEQs) that were calculated using BS IEFs and hepatic concentrations in wild Baikal seals corresponded to only 12-31% of 2005 WHO TEF-derived TEQs. Nevertheless, about 50% of Baikal seals accumulated IEQs over the TCDD-EC50 obtained in this study. This assessment was supported by the enhanced CYP1A1 mRNA expression found in 50% of the specimens contaminated over the TCDD-EC50. These findings suggest that the IEFs proposed from this in vitro assay could be used to predict AHR-mediated responses in wild seals.

Comparison of sampling methods to measure HIV RNA viral load in female genital tract secretions.

PubMed

Jaumdally, Shameem Z; Jones, Heidi E; Hoover, Donald R; Gamieldien, Hoyam; Kriek, Jean-Mari; Langwenya, Nontokozo; Myer, Landon; Passmore, Jo-Ann S; Todd, Catherine S

2017-03-01

How does menstrual cup (MC) compare to other genital sampling methods for HIV RNA recovery? We compared HIV RNA levels between MC, endocervical swab (ECS), and ECS-enriched cervicovaginal lavage (eCVL) specimens in 51 HIV-positive, antiretroviral therapy-naive women at enrollment, 3 and 6 months, with order rotated by visit. Paired comparisons were analyzed with McNemar's exact tests, signed-rank tests, and an extension of Somer's D for pooled analyses across visits. MC specimens had the highest proportion of quantifiable HIV VL at enrollment and month 3, but more MC specimens (n=12.8%) were insufficient for testing, compared with ECS (2%, P=0.006) and eCVL (0%, P<0.001). Among sufficient specimens, median VL was significantly higher for MC (2.62 log 10 copies/mL) compared to ECS (1.30 log 10 copies/mL, P<0.001) and eCVL (1.60 log 10 copies/mL, P<0.001) across visits. MC may be more sensitive than eCVL and CVS, provided insufficient specimens are reduced. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High-resolution characterization of chemical heterogeneity in an alluvial aquifer

USGS Publications Warehouse

Schulmeister, M.K.; Healey, J.M.; Butler, J.J.; McCall, G.W.; Birk, S.

2002-01-01

The high-resolution capabilities of direct push technology were exploited to develop new insights into the hydrochemistry at the margin of an alluvial aquifer. Hydrostratigraphic controls on groundwater flow and contaminant loading were revealed through the combined use of direct push electrical conductivity (EC) logging and geochemical profiling. Vertical and lateral variations in groundwater chemistry were consistent with sedimentary features indicated by EC logs, and were supported by a conceptual model of recharge along the flood plain margin.

QSAR, QSPR and QSRR in Terms of 3-D-MoRSE Descriptors for In Silico Screening of Clofibric Acid Analogues.

PubMed

Di Tullio, Maurizio; Maccallini, Cristina; Ammazzalorso, Alessandra; Giampietro, Letizia; Amoroso, Rosa; De Filippis, Barbara; Fantacuzzi, Marialuigia; Wiczling, Paweł; Kaliszan, Roman

2012-07-01

A series of 27 analogues of clofibric acid, mostly heteroarylalkanoic derivatives, have been analyzed by a novel high-throughput reversed-phase HPLC method employing combined gradient of eluent's pH and organic modifier content. The such determined hydrophobicity (lipophilicity) parameters, log kw , and acidity constants, pKa , were subjected to multiple regression analysis to get a QSRR (Quantitative StructureRetention Relationships) and a QSPR (Quantitative Structure-Property Relationships) equation, respectively, describing these pharmacokinetics-determining physicochemical parameters in terms of the calculation chemistry derived structural descriptors. The previously determined in vitro log EC50 values - transactivation activity towards PPARα (human Peroxisome Proliferator-Activated Receptor α) - have also been described in a QSAR (Quantitative StructureActivity Relationships) equation in terms of the 3-D-MoRSE descriptors (3D-Molecule Representation of Structures based on Electron diffraction descriptors). The QSAR model derived can serve for an a priori prediction of bioactivity in vitro of any designed analogue, whereas the QSRR and the QSPR models can be used to evaluate lipophilicity and acidity, respectively, of the compounds, and hence to rational guide selection of structures of proper pharmacokinetics. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Adenosine A2A receptor agonists with potent antiplatelet activity.

PubMed

Fuentes, Eduardo; Fuentes, Manuel; Caballero, Julio; Palomo, Iván; Hinz, Sonja; El-Tayeb, Ali; Müller, Christa E

2018-05-01

Selected adenosine A 2A receptor agonists (PSB-15826, PSB-12404, and PSB-16301) have been evaluated as new antiplatelet agents. In addition, radioligand-binding studies and receptor-docking experiments were performed in order to explain their differential biological effects on a molecular level. Among the tested adenosine derivatives, PSB-15826 was the most potent compound to inhibit platelet aggregation (EC 50 0.32 ± 0.05 µmol/L) and platelet P-selectin cell-surface localization (EC 50 0.062 ± 0.2 µmol/L), and to increase intraplatelets cAMP levels (EC 50 0.24 ± 0.01 µmol/L). The compound was more active than CGS21680 (EC 50 0.97±0.07 µmol/L) and equipotent to NECA (EC 50 0.31 ± 0.05 µmol/L) in platelet aggregation induced by ADP. In contrast to the results from cAMP assays, K i values determined in radioligand-binding studies were not predictive of the A 2A agonists' antiplatelet activity. Docking studies revealed the key molecular determinants of this new family of adenosine A 2A receptor agonists: differences in activities are related to π-stacking interactions between the ligands and the residue His264 in the extracellular loop of the adenosine A 2A receptor which may result in increased residence times. In conclusion, these results provide an improved understanding of the requirements of antiplatelet adenosine A 2A receptor agonists.

Synthesis and antioxidant evaluation of (S,S)- and (R,R)-secoisolariciresinol diglucosides (SDGs).

PubMed

Mishra, Om P; Simmons, Nicholas; Tyagi, Sonia; Pietrofesa, Ralph; Shuvaev, Vladimir V; Valiulin, Roman A; Heretsch, Philipp; Nicolaou, K C; Christofidou-Solomidou, Melpo

2013-10-01

Secoisolariciresinol diglucosides (SDGs) (S,S)-SDG-1 (major isomer in flaxseed) and (R,R)-SDG-2 (minor isomer in flaxseed) were synthesized from vanillin via secoisolariciresinol (6) and glucosyl donor 7 through a concise route that involved chromatographic separation of diastereomeric diglucoside derivatives (S,S)-8 and (R,R)-9. Synthetic (S,S)-SDG-1 and (R,R)-SDG-2 exhibited potent antioxidant properties (EC50=292.17±27.71 μM and 331.94±21.21 μM, respectively), which compared well with that of natural (S,S)-SDG-1 (EC50=275.24±13.15 μM). These values are significantly lower than those of ascorbic acid (EC50=1129.32±88.79 μM) and α-tocopherol (EC50=944.62±148.00 μM). Compounds (S,S)-SDG-1 and (R,R)-SDG-2 also demonstrated powerful scavenging activities against hydroxyl [natural (S,S)-SDG-1: 3.68±0.27; synthetic (S,S)-SDG-1: 2.09±0.16; synthetic (R,R)-SDG-2: 1.96±0.27], peroxyl [natural (S,S)-SDG-1: 2.55±0.11; synthetic (S,S)-SDG-1: 2.20±0.10; synthetic (R,R)-SDG-2: 3.03±0.04] and DPPH [natural (S,S)-SDG-1: EC50=83.94±2.80 μM; synthetic (S,S)-SDG-1: EC50=157.54±21.30 μM; synthetic (R,R)-SDG-2: EC50=123.63±8.67 μM] radicals. These results confirm previous studies with naturally occurring (S,S)-SDG-1 and establish both (S,S)-SDG-1 and (R,R)-SDG-2 as potent antioxidants and free radical scavengers for potential in vivo use. Copyright © 2013 Elsevier Ltd. All rights reserved.

Preclinical Activity of VX-787, a First-in-Class, Orally Bioavailable Inhibitor of the Influenza Virus Polymerase PB2 Subunit

PubMed Central

Byrn, Randal A.; Jones, Steven M.; Bennett, Hamilton B.; Bral, Chris; Clark, Michael P.; Jacobs, Marc D.; Kwong, Ann D.; Ledeboer, Mark W.; Leeman, Joshua R.; McNeil, Colleen F.; Murcko, Mark A.; Nezami, Azin; Perola, Emanuele; Rijnbrand, Rene; Saxena, Kumkum; Tsai, Alice W.; Zhou, Yi

2014-01-01

VX-787 is a novel inhibitor of influenza virus replication that blocks the PB2 cap-snatching activity of the influenza viral polymerase complex. Viral genetics and X-ray crystallography studies provide support for the idea that VX-787 occupies the 7-methyl GTP (m7GTP) cap-binding site of PB2. VX-787 binds the cap-binding domain of the PB2 subunit with a KD (dissociation constant) of 24 nM as determined by isothermal titration calorimetry (ITC). The cell-based EC50 (the concentration of compound that ensures 50% cell viability of an uninfected control) for VX-787 is 1.6 nM in a cytopathic effect (CPE) assay, with a similar EC50 in a viral RNA replication assay. VX-787 is active against a diverse panel of influenza A virus strains, including H1N1pdm09 and H5N1 strains, as well as strains with reduced susceptibility to neuraminidase inhibitors (NAIs). VX-787 was highly efficacious in both prophylaxis and treatment models of mouse influenza and was superior to the neuraminidase inhibitor, oseltamivir, including in delayed-start-to-treat experiments, with 100% survival at up to 96 h postinfection and partial survival in groups where the initiation of therapy was delayed up to 120 h postinfection. At different doses, VX-787 showed a 1-log to >5-log reduction in viral load (relative to vehicle controls) in mouse lungs. Overall, these favorable findings validate the PB2 subunit of the viral polymerase as a drug target for influenza therapy and support the continued development of VX-787 as a novel antiviral agent for the treatment of influenza infection. PMID:25547360

Preclinical activity of VX-787, a first-in-class, orally bioavailable inhibitor of the influenza virus polymerase PB2 subunit.

PubMed

Byrn, Randal A; Jones, Steven M; Bennett, Hamilton B; Bral, Chris; Clark, Michael P; Jacobs, Marc D; Kwong, Ann D; Ledeboer, Mark W; Leeman, Joshua R; McNeil, Colleen F; Murcko, Mark A; Nezami, Azin; Perola, Emanuele; Rijnbrand, Rene; Saxena, Kumkum; Tsai, Alice W; Zhou, Yi; Charifson, Paul S

2015-03-01

VX-787 is a novel inhibitor of influenza virus replication that blocks the PB2 cap-snatching activity of the influenza viral polymerase complex. Viral genetics and X-ray crystallography studies provide support for the idea that VX-787 occupies the 7-methyl GTP (m(7)GTP) cap-binding site of PB2. VX-787 binds the cap-binding domain of the PB2 subunit with a KD (dissociation constant) of 24 nM as determined by isothermal titration calorimetry (ITC). The cell-based EC50 (the concentration of compound that ensures 50% cell viability of an uninfected control) for VX-787 is 1.6 nM in a cytopathic effect (CPE) assay, with a similar EC50 in a viral RNA replication assay. VX-787 is active against a diverse panel of influenza A virus strains, including H1N1pdm09 and H5N1 strains, as well as strains with reduced susceptibility to neuraminidase inhibitors (NAIs). VX-787 was highly efficacious in both prophylaxis and treatment models of mouse influenza and was superior to the neuraminidase inhibitor, oseltamivir, including in delayed-start-to-treat experiments, with 100% survival at up to 96 h postinfection and partial survival in groups where the initiation of therapy was delayed up to 120 h postinfection. At different doses, VX-787 showed a 1-log to >5-log reduction in viral load (relative to vehicle controls) in mouse lungs. Overall, these favorable findings validate the PB2 subunit of the viral polymerase as a drug target for influenza therapy and support the continued development of VX-787 as a novel antiviral agent for the treatment of influenza infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Prediction of kinase-inhibitor binding affinity using energetic parameters

PubMed Central

Usha, Singaravelu; Selvaraj, Samuel

2016-01-01

The combination of physicochemical properties and energetic parameters derived from protein-ligand complexes play a vital role in determining the biological activity of a molecule. In the present work, protein-ligand interaction energy along with logP values was used to predict the experimental log (IC50) values of 25 different kinase-inhibitors using multiple regressions which gave a correlation coefficient of 0.93. The regression equation obtained was tested on 93 kinase-inhibitor complexes and an average deviation of 0.92 from the experimental log IC50 values was shown. The same set of descriptors was used to predict binding affinities for a test set of five individual kinase families, with correlation values > 0.9. We show that the protein-ligand interaction energies and partition coefficient values form the major deterministic factors for binding affinity of the ligand for its receptor. PMID:28149052

Dose-response effects of clove oil from Syzygium aromaticum on the root-knot nematode Meloidogyne incognita.

PubMed

Meyer, Susan L F; Lakshman, Dilip K; Zasada, Inga A; Vinyard, Bryan T; Chitwood, David J

2008-03-01

Clove oil, derived from the plant Syzygium aromaticum (L.) Merr. & Perry, is active against various organisms, and was prepared in a soy lecithin/detergent formulation to determine concentrations active against the root-knot nematode Meloidogyne incognita (Kofoid and White) Chitwood. In microwell assays, the mean effective clove oil concentration that reduced egg hatch by 50% (EC(50)) was 0.097% (v/v) clove oil; the EC(50) for second-stage juvenile (J2) viability was 0.145% clove oil (compared with carrier control treatments). Volatiles from 5.0% clove oil reduced nematode egg hatch in water by 30%, and decreased viability of hatched J2 by as much as 100%. Reductions were not as large with nematodes in carrier. In soil trials with J2 recovered from Baermann funnels, the EC(50) = 0.192% clove oil (compared with water controls). The results demonstrated that the tested formulation is active against M. incognita eggs and J2, that the EC(50) values for J2 in the microwell studies and the soil recovery tests were similar to each other and that direct contact with the clove oil is needed for optimal management results with this natural product. (c) 2008 Society of Chemical Industry.

Shear velocity estimates on the inner shelf off Grays Harbor, Washington, USA

USGS Publications Warehouse

Sherwood, C.R.; Lacy, J.R.; Voulgaris, G.

2006-01-01

Shear velocity was estimated from current measurements near the bottom off Grays Harbor, Washington between May 4 and June 6, 2001 under mostly wave-dominated conditions. A downward-looking pulse-coherent acoustic Doppler profiler (PCADP) and two acoustic-Doppler velocimeters (field version; ADVFs) were deployed on a tripod at 9-m water depth. Measurements from these instruments were used to estimate shear velocity with (1) a modified eddy-correlation (EC) technique, (2) the log-profile (LP) method, and (3) a dissipation-rate method. Although values produced by the three methods agreed reasonably well (within their broad ranges of uncertainty), there were important systematic differences. Estimates from the EC method were generally lowest, followed by those from the inertial-dissipation method. The LP method produced the highest values and the greatest scatter. We show that these results are consistent with boundary-layer theory when sediment-induced stratification is present. The EC method provides the most fundamental estimate of kinematic stress near the bottom, and stratification causes the LP method to overestimate bottom stress. These results remind us that the methods are not equivalent and that comparison among sites and with models should be made carefully. ?? 2006 Elsevier Ltd. All rights reserved.

Toxicity assessment of common xenobiotic compounds on municipal activated sludge: comparison between respirometry and Microtox.

PubMed

Ricco, Giuseppina; Tomei, M C M Concetta; Ramadori, Roberto; Laera, Giuseppe

2004-04-01

The toxicity of four xenobiotic compounds 3,5-dichlorophenol, formaldehyde, 4-nitrophenol and dichloromethane, representative of industrial wastewater contaminants was evaluated by a simple respirometric procedure set up on the basis of OECD Method 209 and by the Microtox bioassay. Very good reproducibility was observed for both methods, the variation coefficients being in the range of 2-10% for the respirometric procedure and 6-15% for Microtox, values that can be considered very good for a biological method. Comparison of EC(50) data obtained with the two methods shows that in both cases 3,5-dichlorophenol is more toxic than other compounds investigated and dichloromethane has a very low toxicity value. Intermediate EC(50) values were found for the two other chemicals, formaldehyde and 4-nitrophenol. Moreover, the Microtox EC(50) values are generally lower (except for dichloromethane) than the respirometric ones: these differences could be explained by the fact that the Microtox method uses a pure culture of marine species and, therefore, should not necessarily be expected to behave like a community of activated sludge bacteria. In conclusion, both methods can be usefully applied for toxicity detection in wastewater treatment plants but it is advisable to take into account that Microtox is more sensitive than respirometry in estimating the acute toxicity effect on the biomass operating in the plant.

Antibacterial Effects of Amoxicillin-Clavulanate against Streptococcus pneumoniae and Haemophilus influenzae Strains for Which MICs Are High, in an In Vitro Pharmacokinetic Model

PubMed Central

MacGowan, Alasdair P.; Noel, Alan R.; Rogers, Chris A.; Bowker, Karen E.

2004-01-01

The antibacterial effect of amoxicillin-clavulanate in two formulations, pharmacokinetically enhanced 16:1 amoxicillin-clavulanate twice a day (b.i.d.) and standard 7:1 amoxicillin-clavulanate b.i.d., were studied in an in vitro pharmacokinetic model of infection. Five strains of Streptococcus pneumoniae and two of Haemophilus influenzae, all associated with raised MICs (2 to 8 mg/liter), were used. The antibacterial effect was measured over 24 h by the area under the bacterial kill curve (AUBKC) and the log change in viable count at 24 h (Δ24). A high 108 CFU/ml and low 106 CFU/ml initial inocula were used. Employing the Δ24 effect measure, the time above MIC (T>MIC) 50% maximum effect (EC50) for S. pneumoniae was in the range 21 to 28% with an 80% maximal response of 41 to 51%, for the AUBKC measure, the value was 26 to 39%, irrespective of inoculum. For H. influenzae, the T>MIC EC50 was 28 to 37%, and the 80% maximum response was 32 to 48% for the Δ24 measure and 20 to 48% for AUBKC. The maximum response occurred at a T>MIC of 50 to 60% for both species and inocula. The S. pneumoniae data were analyzed by analysis of variance to assess the effect of inoculum, formulation, and MIC on antibacterial effect. Standard and enhanced formulations had different effects depending on MIC, with the standard formulation less effective at higher amoxicillin-clavulanate MICs. This is explained by the greater T>MICs of the enhanced formulation. Although resistant to amoxicillin-clavulanate by conventional breakpoints, S. pneumoniae and H. influenzae strains for which MICs are 2 or 4 mg/liter may well respond to therapy with pharmacokinetically enhanced formulation amoxicillin-clavulanate. PMID:15215115

Antibacterial effects of amoxicillin-clavulanate against Streptococcus pneumoniae and Haemophilus influenzae strains for which MICs are high, in an in vitro pharmacokinetic model.

PubMed

MacGowan, Alasdair P; Noel, Alan R; Rogers, Chris A; Bowker, Karen E

2004-07-01

The antibacterial effect of amoxicillin-clavulanate in two formulations, pharmacokinetically enhanced 16:1 amoxicillin-clavulanate twice a day (b.i.d.) and standard 7:1 amoxicillin-clavulanate b.i.d., were studied in an in vitro pharmacokinetic model of infection. Five strains of Streptococcus pneumoniae and two of Haemophilus influenzae, all associated with raised MICs (2 to 8 mg/liter), were used. The antibacterial effect was measured over 24 h by the area under the bacterial kill curve (AUBKC) and the log change in viable count at 24 h (Delta24). A high 10(8) CFU/ml and low 10(6) CFU/ml initial inocula were used. Employing the Delta24 effect measure, the time above MIC (T>MIC) 50% maximum effect (EC(50)) for S. pneumoniae was in the range 21 to 28% with an 80% maximal response of 41 to 51%, for the AUBKC measure, the value was 26 to 39%, irrespective of inoculum. For H. influenzae, the T>MIC EC(50) was 28 to 37%, and the 80% maximum response was 32 to 48% for the Delta24 measure and 20 to 48% for AUBKC. The maximum response occurred at a T>MIC of 50 to 60% for both species and inocula. The S. pneumoniae data were analyzed by analysis of variance to assess the effect of inoculum, formulation, and MIC on antibacterial effect. Standard and enhanced formulations had different effects depending on MIC, with the standard formulation less effective at higher amoxicillin-clavulanate MICs. This is explained by the greater T>MICs of the enhanced formulation. Although resistant to amoxicillin-clavulanate by conventional breakpoints, S. pneumoniae and H. influenzae strains for which MICs are 2 or 4 mg/liter may well respond to therapy with pharmacokinetically enhanced formulation amoxicillin-clavulanate.

Pinosylvin and monomethylpinosylvin, constituents of an extract from the knot of Pinus sylvestris, reduce inflammatory gene expression and inflammatory responses in vivo.

PubMed

Laavola, Mirka; Nieminen, Riina; Leppänen, Tiina; Eckerman, Christer; Holmbom, Bjarne; Moilanen, Eeva

2015-04-08

Scots pine (Pinus sylvestris) is known to be rich in phenolic compounds, which may have anti-inflammatory properties. The present study investigated the anti-inflammatory effects of a knot extract from P. sylvestris and two stilbenes, pinosylvin and monomethylpinosylvin, isolated from the extract. Inflammation is characterized by increased release of pro-inflammatory and regulatory mediators including nitric oxide (NO) produced by the inducible nitric oxide synthase (iNOS) pathway. The knot extract (EC50 values of 3 and 3 μg/mL) as well as two of its constituents, pinosylvin (EC50 values of 13 and 15 μM) and monomethylpinosylvin (EC50 values of 8 and 12 μM), reduced NO production and iNOS expression in activated macrophages. They also inhibited the production of inflammatory cytokines IL-6 and MCP-1. More importantly, pinosylvin and monomethylpinosylvin exerted a clear anti-inflammatory effect (80% inhibition at the dose of 100 mg/kg) in the standard in vivo model, carrageenan-induced paw inflammation in the mouse, with the effect being comparable to that of a known iNOS inhibitor L-NIL. The results reveal that the Scots pine stilbenes pinosylvin and monomethylpinosylvin are potential anti-inflammatory compounds.

Population pharmacokinetics and pharmacodynamics of bivalirudin in young healthy Chinese volunteers.

PubMed

Zhang, Dong-mei; Wang, Kun; Zhao, Xia; Li, Yun-fei; Zheng, Qing-shan; Wang, Zi-ning; Cui, Yi-min

2012-11-01

To investigate the population pharmacokinetics (PK) and pharmacodynamics (PD) of bivalirudin, a synthetic bivalent direct thrombin inhibitor, in young healthy Chinese subjects. Thirty-six young healthy volunteers were randomly assigned into 4 groups received bivalirudin 0.5 mg/kg, 0.75 mg/kg, and 1.05 mg/kg intravenous bolus, 0.75 mg/kg intravenous bolus followed by 1.75 mg/kg intravenous infusion per hour for 4 h. Blood samples were collected to measure bivalirudin plasma concentration and activated clotting time (ACT). Population PK-PD analysis was performed using the nonlinear mixed-effects model software NONMEM. The final models were validated with bootstrap and prediction-corrected visual predictive check (pcVPC) approaches. The final PK model was a two-compartment model without covariates. The typical PK population values of clearance (CL), apparent distribution volume of the central-compartment (V(1)), inter-compartmental clearance (Q) and apparent distribution volume of the peripheral compartment (V(2)) were 0.323 L·h(-1)·kg(-1), 0.086 L/kg, 0.0957 L·h(-1)·kg(-1), and 0.0554 L/kg, respectively. The inter-individual variabilities of these parameters were 14.8%, 24.2%, fixed to 0% and 15.6%, respectively. The final PK-PD model was a sigmoid E(max) model without the Hill coefficient. In this model, a covariate, red blood cell count (RBC(*)), had a significant effect on the EC(50) value. The typical PD population values of maximum effect (E(max)), EC(50), baseline ACT value (E(0)) and the coefficient of RBC(*) on EC(50) were 318 s, 2.44 mg/L, 134 s and 1.70, respectively. The inter-individual variabilities of E(max), EC(50), and E(0) were 6.80%, 46.4%, and 4.10%, respectively. Population PK-PD models of bivalirudin in healthy young Chinese subjects have been developed, which may provide a reference for future use of bivalirudin in China.

Male patients require higher optimal effect-site concentrations of propofol during i-gel insertion with dexmedetomidine 0.5 μg/kg.

PubMed

Choi, Jung Ju; Kim, Ji Young; Lee, Dongchul; Chang, Young Jin; Cho, Noo Ree; Kwak, Hyun Jeong

2016-03-22

The pharmacokinetics and pharmacodynamics of an anesthetic drug may be influenced by gender. The purpose of this study was to compare effect-site half maximal effective concentrations (EC50) of propofol in male and female patients during i-gel insertion with dexmedetomidine 0.5 μg/kg without muscle relaxants. Forty patients, aged 20-46 years of ASA physical status I or II, were allocated to one of two groups by gender (20 patients per group). After the infusion of dexmedetomidine 0.5 μg/kg over 2 min, anesthesia was induced with a pre-determined effect-site concentration of propofol by target controlled infusion. Effect-site EC50 values of propofol for successful i-gel insertion were determined using the modified Dixon's up-and-down method. Mean effect-site EC50 ± SD of propofol for successful i-gel insertion was significantly higher for men than women (5.46 ± 0.26 μg/ml vs. 3.82 ± 0.34 μg/ml, p < 0.01). The EC50 of propofol in men was approximately 40% higher than in women. Using isotonic regression with a bootstrapping approach, the estimated EC50 (95% confidence interval) of propofol was also higher in men [5.32 (4.45-6.20) μg/ml vs. 3.75 (3.05-4.43) μg/ml]. The estimated EC95 (95% confidence interval) of propofol in men and women were 5.93 (4.72-6.88) μg/ml and 4.52 (3.02-5.70) μg/ml, respectively. During i-gel insertion with dexmedetomidine 0.5 μg/kg without muscle relaxant, male patients had higher effect-site EC50 for propofol using Schnider's model. Based on the results of this study, patient gender should be considered when determining the optimal dose of propofol during supraglottic airway insertion. ClinicalTrials.gov identifier: NCT02268656. Registered August 26, 2014.

Characterization of the Maize Stalk Rot Pathogens Fusarium subglutinans and F. temperatum and the Effect of Fungicides on Their Mycelial Growth and Colony Formation

PubMed Central

Shin, Jong-Hwan; Han, Joon-Hee; Lee, Ju Kyong; Kim, Kyoung Su

2014-01-01

Maize is a socioeconomically important crop in many countries. Recently, a high incidence of stalk rot disease has been reported in several maize fields in Gangwon province. In this report, we show that maize stalk rot is associated with the fungal pathogens Fusarium subglutinans and F. temperatum. Since no fungicides are available to control these pathogens on maize plants, we selected six fungicides (tebuconazole, difenoconazole, fluquinconazole, azoxystrobin, prochloraz and kresoxim-methyl) and examined their effectiveness against the two pathogens. The in vitro antifungal effects of the six fungicides on mycelial growth and colony formation were investigated. Based on the inhibition of mycelial growth, the most toxic fungicide was tebuconazole with 50% effective concentrations (EC50) of <0.1 μg/ml and EC90 values of 0.9 μg/ml for both pathogens, while the least toxic fungicide was azoxystrobin with EC50 values of 0.7 and 0.5 μg/ml for F. subglutinans and F. temperatum, respectively, and EC90 values of >3,000 μg/ml for both pathogens. Based on the inhibition of colony formation by the two pathogens, kresoxim-methyl was the most toxic fungicide with complete inhibition of colony formation at concentrations of 0.1 and 0.01 μg/ml for F. subglutinans and F. temperatum, respectively, whereas azoxystrobin was the least toxic fungicide with complete inhibition of colony formation at concentrations >3,000 μg/ml for both pathogens. PMID:25506304

Binding site and affinity prediction of general anesthetics to protein targets using docking.

PubMed

Liu, Renyu; Perez-Aguilar, Jose Manuel; Liang, David; Saven, Jeffery G

2012-05-01

The protein targets for general anesthetics remain unclear. A tool to predict anesthetic binding for potential binding targets is needed. In this study, we explored whether a computational method, AutoDock, could serve as such a tool. High-resolution crystal data of water-soluble proteins (cytochrome C, apoferritin, and human serum albumin), and a membrane protein (a pentameric ligand-gated ion channel from Gloeobacter violaceus [GLIC]) were used. Isothermal titration calorimetry (ITC) experiments were performed to determine anesthetic affinity in solution conditions for apoferritin. Docking calculations were performed using DockingServer with the Lamarckian genetic algorithm and the Solis and Wets local search method (http://www.dockingserver.com/web). Twenty general anesthetics were docked into apoferritin. The predicted binding constants were compared with those obtained from ITC experiments for potential correlations. In the case of apoferritin, details of the binding site and their interactions were compared with recent cocrystallization data. Docking calculations for 6 general anesthetics currently used in clinical settings (isoflurane, sevoflurane, desflurane, halothane, propofol, and etomidate) with known 50% effective concentration (EC(50)) values were also performed in all tested proteins. The binding constants derived from docking experiments were compared with known EC(50) values and octanol/water partition coefficients for the 6 general anesthetics. All 20 general anesthetics docked unambiguously into the anesthetic binding site identified in the crystal structure of apoferritin. The binding constants for 20 anesthetics obtained from the docking calculations correlate significantly with those obtained from ITC experiments (P = 0.04). In the case of GLIC, the identified anesthetic binding sites in the crystal structure are among the docking predicted binding sites, but not the top ranked site. Docking calculations suggest a most probable binding site located in the extracellular domain of GLIC. The predicted affinities correlated significantly with the known EC(50) values for the 6 frequently used anesthetics in GLIC for the site identified in the experimental crystal data (P = 0.006). However, predicted affinities in apoferritin, human serum albumin, and cytochrome C did not correlate with these 6 anesthetics' known experimental EC(50) values. A weak correlation between the predicted affinities and the octanol/water partition coefficients was observed for the sites in GLIC. We demonstrated that anesthetic binding sites and relative affinities can be predicted using docking calculations in an automatic docking server (AutoDock) for both water-soluble and membrane proteins. Correlation of predicted affinity and EC(50) for 6 frequently used general anesthetics was only observed in GLIC, a member of a protein family relevant to anesthetic mechanism.

Fast algal eco-toxicity assessment: Influence of light intensity and exposure time on Chlorella vulgaris inhibition by atrazine and DCMU.

PubMed

Camuel, Alexandre; Guieysse, Benoit; Alcántara, Cynthia; Béchet, Quentin

2017-06-01

In order to develop a rapid assay suitable for algal eco-toxicity assessments under conditions representative of natural ecosystems, this study evaluated the short-term (<1h) response of algae exposed to atrazine and DCMU using oxygen productivity measurements. When Chlorella vulgaris was exposed to these herbicides under 'standard' low light intensity (as prescribed by OECD201 guideline), the 20min-EC 50 values recorded via oxygen productivity (atrazine: 1.32±0.07μM; DCMU: 0.31±0.005μM) were similar the 96-h EC 50 recorded via algal growth (atrazine: 0.56μM; DCMU: 0.41μM), and within the range of values reported in the literature. 20min-EC50 values increased by factors of 3.0 and 2.1 for atrazine and DCMU, respectively, when light intensity increased from 60 to 1400μmolm -2 s -1 of photosynthetically active radiation, or PAR. Further investigation showed that exposure time significantly also impacted the sensitivity of C. vulgaris under high light intensity (>840μmolm -2 s -1 as PAR) as the EC 50 for atrazine and DCMU decreased by up to 6.2 and 2.1 folds, respectively, after 50min of exposure at a light irradiance of 1400μmolm -2 s -1 as PAR. This decrease was particularly marked at high light intensities and low algae concentrations and is explained by the herbicide disruption of the electron transfer chain triggering photo-inhibition at high light intensities. Eco-toxicity assessments aiming to understand the potential impact of toxic compounds on natural ecosystems should therefore be performed over sufficient exposure times (>20min for C. vulgaris) and under light intensities relevant to these ecosystems. Copyright © 2017 Elsevier Inc. All rights reserved.

The unicellular fungal tool RhoTox for risk assessments in groundwater systems.

PubMed

Lategan, Maria Josie; Klare, William; Kidd, Sarah; Hose, Grant C; Nevalainen, Helena

2016-10-01

The recent inclusion of yeasts in environmental monitoring recognizes their ecological significance and sensitivity to toxicants. Here we present a robust and simple two-step toxicity assay and demonstrate the sensitivity of an ubiquitous groundwater yeast, Rhodotorula minuta, to a range of metals and metalloids. The test species was sensitive to copper with a 24h EC50 of 35µg Cu/L, followed in order of decreasing sensitivity by zinc, chromium (VI) and arsenic (EC50 4.40mg As (III)/L). The strain demonstrated an unexpected tolerance to chromium (VI), having an EC50 value (3.45mg Cr (VI)/L) similar to that of arsenic. The inclusion of a unicellular, microbial test-species into the suite of existing multicellular test species for toxicity evaluation is a key step towards strengthening the assessment of risk for groundwater ecosystems. Copyright © 2016 Elsevier Inc. All rights reserved.

Synthetic strategy and antiviral evaluation of diamide containing heterocycles targeting dengue and yellow fever virus.

PubMed

Saudi, Milind; Zmurko, Joanna; Kaptein, Suzanne; Rozenski, Jef; Gadakh, Bharat; Chaltin, Patrick; Marchand, Arnaud; Neyts, Johan; Van Aerschot, Arthur

2016-10-04

High-throughput screening of a subset of the CD3 chemical library (Centre for Drug Design and Discovery; KU Leuven) provided us with a lead compound 1, displaying low micromolar potency against dengue virus and yellow fever virus. Within a project aimed at discovering new inhibitors of flaviviruses, substitution of its central imidazole ring led to synthesis of variably substituted pyrazine dicarboxylamides and phthalic diamides, which were evaluated in cell-based assays for cytotoxicity and antiviral activity against the dengue virus (DENV) and yellow fever virus (YFV). Fourteen compounds inhibited DENV replication (EC50 ranging between 0.5 and 3.4 μM), with compounds 6b and 6d being the most potent inhibitors (EC50 0.5 μM) with selectivity indices (SI) > 235. Compound 7a likewise exhibited anti-DENV activity with an EC50 of 0.5 μM and an SI of >235. In addition, good antiviral activity of seven compounds in the series was also noted against the YFV with EC50 values ranging between 0.4 and 3.3 μM, with compound 6n being the most potent for this series with an EC50 0.4 μM and a selectivity index of >34. Finally, reversal of one of the central amide bonds as in series 13 proved deleterious to the inhibitory activity. Copyright © 2016 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Effect of triclosan on reproduction, DNA damage and heat shock protein gene expression of the earthworm Eisenia fetida.

PubMed

Lin, Dasong; Li, Ye; Zhou, Qixing; Xu, Yingming; Wang, Di

2014-12-01

Triclosan (TCS) is released into the terrestrial environment via the application of sewage sludge and reclaimed water to agricultural land. More attention has been paid to its effect on non-target soil organisms. In the present study, chronic toxic effects of TCS on earthworms at a wide range of concentrations were investigated. The reproduction, DNA damage, and expression levels of heat shock protein (Hsp70) gene of earthworms were studied as toxicity endpoints. The results showed that the reproduction of earthworms were significantly reduced (p < 0.05) after exposure to the concentrations ranges from 50 to 300 mg kg(-1), with a half-maximal effective concentration (EC50) of 142.11 mg kg(-1). DNA damage, detected by the comet assay, was observed and there was a clear significant (R(2) = 0.941) relationship between TCS concentrations and DNA damage, with the EC50 value of 8.85 mg kg(-1). The expression levels of Hsp70 gene of earthworms were found to be up-regulated under the experimental conditions. The expression level of hsp70 gene increased, up to about 2.28 folds that in the control at 50 mg kg(-1). The EC50 value based on the Hsp70 biomarker was 1.79 mg kg(-1). Thus, among the three toxicity endpoints, the Hsp70 gene was more sensitive to TCS in soil.

Toxicity of metalaxyl, azoxystrobin, dimethomorph, cymoxanil, zoxamide and mancozeb to Phytophthora infestans isolates from Serbia.

PubMed

Rekanović, Emil; Potočnik, Ivana; Milijašević-Marčić, Svetlana; Stepanović, Miloš; Todorović, Biljana; Mihajlović, Milica

2012-01-01

A study of the in vitro sensitivity of 12 isolates of Phytophthora infestans to metalaxyl, azoxystrobin, dimethomorph, cymoxanil, zoxamide and mancozeb, was conducted. The isolates derived from infected potato leaves collected at eight different localities in Serbia during 2005-2007. The widest range of EC(50) values for mycelial growth of the isolates was recorded for metalaxyl. They varied from 0.3 to 3.9 μg mL(-1) and were higher than those expected in a susceptible population of P. infestans. The EC(50) values of the isolates were 0.16-0.30 μg mL(-1) for dimethomorph, 0.27-0.57 μg mL(-1) for cymoxanil, 0.0026-0.0049 μg mL(-1) for zoxamide and 2.9-5.0 μg mL(-1) for mancozeb. The results indicated that according to effective concentration (EC(50)) the 12 isolates of P. infestans were sensitive to azoxystrobin (0.019-0.074 μg mL(-1)), and intermediate resistant to metalaxyl, dimethomorph and cymoxanil. According to resistance factor, all P. infestans isolates were sensitive to dimethomorph, cymoxanil, mancozeb and zoxamide, 58.3% of isolates were sensitive to azoxystrobin and 50% to metalaxyl. Gout's scale indicated that 41.7% isolates were moderately sensitive to azoxystrobin and 50% to metalaxyl.

Free radical scavenging actions of three Trifolium species in the protection of blood plasma antioxidant capacity in vitro.

PubMed

Kolodziejczyk-Czepas, Joanna; Nowak, Pawel; Moniuszko-Szajwaj, Barbara; Kowalska, Iwona; Stochmal, Anna

2015-01-01

Three clover [Trifolium L. (Leguminosae)] species were selected on the basis of data from traditional medicine, phytochemical profiles, and agricultural significance. The in vitro evaluations of free radical scavenging properties, ferric reducing abilities, and antioxidant effects of extracts from T. pratense L. (crude extract and phenolic fraction), T. pallidum L., and T. scabrum L. (phenolic fractions) were performed. Activities of the Trifolium extracts were determined at their final concentrations of 1.5-50 µg/ml. Free radical scavenging properties of methanol extract solutions were estimated by the reduction of DPPH(•) and ABTS(•) radicals. Measurements of the total antioxidant capacity (TAC) were carried out to assess the antioxidant activities of the extracts in human blood plasma under conditions of oxidative stress, induced by 200 μM peroxynitrite. The phenolic fraction of T. pratense displayed the strongest ABTS(•) and DPPH(•) radical scavenging effects (EC50 value of 21.69 and 12.27 µg/ml, respectively). The EC50 value for T. pallidum extract attained 29.77 and 30.06 µg/ml. The two remaining extracts were less potent scavengers (EC50 value higher than 50 µg/ml). Similar differences were obtained during evaluation of the ferric reducing abilities. Analysis of antioxidant properties of the extracts in blood plasma did not provide such evident differences in their actions, however, it indicated that the T. pratense phenolic fraction displayed the strongest effect. The examined Trifolium extracts partly protected blood plasma and enhanced its non-enzymatic antioxidant defense against harmful action of peroxynitrite in vitro.

Acute oral and percutaneous toxicity of pesticides to mallards: Correlations with mammalian toxicity data

USGS Publications Warehouse

Hudson, R.H.; Haegele, M.A.; Tucker, R.K.

1979-01-01

Acute oral (po) and 24-hr percutaneous (perc) LD50 values for 21 common pesticides (19 anticholinesterases, of which 18 were organophosphates, and one was a carbamate; one was an organochlorine central nervous system stimulant; and one was an organonitrogen pneumotoxicant) were determined in mallards (Anas platyrhynchos). Three of the pesticides tested were more toxic percutaneously than orally. An index to the percutaneous hazard of a pesticide, the dermal toxicity index (DTI = po LD50/perc LD50 ? 100), was also calculated for each pesticide. These toxicity values in mallards were compared with toxicity data for rats from the literature. Significant positive correlations were found between log po and log percutaneous LD50 values in mallards (r = 0.65, p 0.10). Variations in percutaneous methodologies are discussed with reference to interspecies variation in toxicity values. It is recommended that a mammalian DTI value approaching 30 be used as a guideline for the initiation of percutaneous toxicity studies in birds, when the po LD50 and/or projected percutaneous LD50 are less than expected field exposure levels.

Antifouling Activity towards Mussel by Small-Molecule Compounds from a Strain of Vibrio alginolyticus Bacterium Associated with Sea Anemone Haliplanella sp.

PubMed

Wang, Xiang; Huang, Yanqiu; Sheng, Yanqing; Su, Pei; Qiu, Yan; Ke, Caihuan; Feng, Danqing

2017-03-28

Mussels are major fouling organisms causing serious technical and economic problems. In this study, antifouling activity towards mussel was found in three compounds isolated from a marine bacterium associated with the sea anemone Haliplanella sp. This bacterial strain, called PE2, was identified as Vibrio alginolyticus using morphology, biochemical tests, and phylogenetic analysis based on sequences of 16S rRNA and four housekeeping genes ( rpoD, gyrB, rctB, and toxR ). Three small-molecule compounds (indole, 3-formylindole, and cyclo (Pro-Leu)) were purified from the ethyl acetate extract of V. alginolyticus PE2 using column chromatography techniques. They all significantly inhibited byssal thread production of the green mussel Perna viridis , with EC 50 values of 24.45 μg/ml for indole, 50.07 μg/ml for 3-formylindole, and 49.24 μg/ml for cyclo (Pro-Leu). Previous research on the antifouling activity of metabolites from marine bacteria towards mussels is scarce. Indole, 3-formylindole and cyclo (Pro-Leu) also exhibited antifouling activity against settlement of the barnacle Balanus albicostatus (EC 50 values of 8.84, 0.43, and 11.35 μg/ml, respectively) and the marine bacterium Pseudomonas sp. (EC 50 values of 42.68, 69.68, and 39.05 μg/ml, respectively). These results suggested that the three compounds are potentially useful for environmentally friendly mussel control and/or the development of new antifouling additives that are effective against several biofoulers.

A comparative study of functional 5-HT4 receptors in human colon, rat oesophagus and rat ileum.

PubMed Central

McLean, P. G.; Coupar, I. M.; Molenaar, P.

1995-01-01

1. The pharmacological properties of 5-hydroxytryptamine (5-HT), the 5-HT4 receptor agonists, DAU 6236 and SC 53116 and the 5-HT4 receptor antagonist, GR 1130808, were studied in the rat oesophagus, rat ileum and human colon. 2. 5-HT relaxed the longitudinal muscle of the rat oesophagus and rat ileum and the circular muscle of the human colon. Absolute values of relaxation were measured and showed the order of the maximum responses, rat oesophagus >> human colon > rat ileum with EC50 values of 189 +/- 15 nM, 157 +/- 4 nM, 306 +/- 72 nM, respectively. 5-HT also inhibited the spontaneous contractions of the human colon with an EC50 value of 119 +/- 1 nM. The effect of 5-HT on the human colon was not affected by methysergide (10 microM) or ondansetron (1 microM). 3. The use of the uptake and metabolism inhibitors, cocaine (30 microM) and pargyline (100 microM), did not increase the potency of 5-HT in the rat oesophagus or human colon. In the rat oesophagus, cocaine (30 microM) produced a reduction in carbachol-induced tone of 22.2 +/- 0.6% and reduced the 5-HT maximum effect by 52.0 +/- 0.4%. 4. The compounds, DAU 6236 and SC 53116, showed a different pattern of potencies and efficacies in the rat oesophagus, rat ileum and human colon compared to 5-HT. DAU 6236 relaxed the human colonic circular muscle with an EC50 value of 129 +/- 16 nM but its efficacy was less than that of 5-HT. DAU 6236 (1 microM) also antagonized the 5-HT-induced relaxation of the human colon with a dose-ratio of 9.9. In the rat oesophagus and rat ileum, DAU 6236 was inactive in the majority of tissues. In the minority of oesophagus tissues that did respond the EC50 value was 1.2 +/- 0.7 microM. DAU 6236 also antagonized the effect of 5-HT in the rat oesophagus in a non-surmountable fashion. SC 53116 relaxed the rat oesophagus with an EC50 value of 91 +/- 4 nM, with an efficacy less than that observed to 5-HT; however, at 200 nM it did not antagonize the 5-HT-induced relaxation of the rat oesophagus. SC 53116 showed no agonist activity in the rat ileum and human colon, but at 1 microM it did antagonize the effect of 5-HT in the human colon with a dose-ratio of 11.3 +/- 0.3.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7647983

Inactivation of Listeria monocytogenes, Salmonella spp. and Escherichia coli O157:H7 on cantaloupes by octenidine dihydrochloride.

PubMed

Upadhyay, Abhinav; Chen, Chi-Hung; Yin, Hsinbai; Upadhyaya, Indu; Fancher, Samantha; Liu, Yanyan; Nair, Meera Surendran; Jankelunas, Leanne; Patel, Jitendra R; Venkitanarayanan, Kumar

2016-09-01

The efficacy of a new generation disinfectant, octenidine dihydrochloride (OH), as wash and coating treatments for reducing Listeria monocytogenes (LM), Salmonella spp. (SAL), and Escherichia coli O157:H7 (EC) on cantaloupe was investigated. Cantaloupe rind plugs inoculated separately with the three bacterial species (∼8 log CFU/cm(2)) were washed for 1, 3, 5 min at 25 °C in water, or chlorine (200 ppm), ethanol (1%), OH (0.01, 0.05, 0.1%) and surviving populations were measured after treatment. Additionally, inoculated cantaloupe rind plugs were coated with 2% chitosan or chitosan containing OH (0.01, 0.05, 0.1%) and sampled for surviving pathogens. Subsequently, the antimicrobial efficacy of OH wash and coating (0.1, 0.2%) on whole cantaloupes was determined. All OH wash reduced LM, SAL, and EC on cantaloupe rinds by > 5 log CFU/cm(2) by 2 min, and reduced populations to undetectable levels (below 2 log CFU/cm(2)) by 5 min (P < 0.05). Similarly, OH coating on cantaloupe rinds reduced the pathogens by 3-5 log /cm(2) (P < 0.05). Washing and coating whole cantaloupes with OH reduced the three pathogens by at least 5 log and 2 log CFU/cm(2), respectively (P < 0.05). Results suggest that OH could be used as antimicrobial wash and coating to reduce LM, SAL, and EC on cantaloupes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bio-efficacy evaluation of nanoformulations of β-cyfluthrin against Callosobruchus maculatus (Coleoptera: Bruchidae).

PubMed

Loha, Kumelachew Mulu; Shakil, Najam A; Kumar, Jitendra; Singh, Manish K; Srivastava, Chitra

2012-01-01

In the present investigation, bioefficacy of developed β-cyfluthrin formulations, utilizing laboratory synthesized poly(ethylene glycols) based amphiphilic copolymers, were evaluated against Callosobruchus maculatus (Coleoptera: Bruchidae). The bioefficacy data indicated that the formulations developed by utilizing polymers having PEG - 1500 (3c) and PEG - 2000 (3d) as the hydrophilic segment showed greater efficacy after 14 days as evident from EC(50) values (2.2 and 1.58 mg L(-1) respectively). Also, release from the commercial SC formulation was faster than developed formulations as the commercial formulation had the lowest EC(50) value on the first day (0.51 mg L(-1)). The mean EC(50) of the commercial formulation against C. maculatus was quite high as compared to those of developed formulations. The results suggest that depending upon the polymer matrix used, the application rate of β-cyfluthrin can be optimized to achieve insect control at the desired level and period. The results described in this paper are promising and provide a comparison of developed formulations with the commercial one showing an earlier degradation of β-cyfluthrin in the latter and relatively prolonged activity in the former.

Synthesis and anthelmintic activity of arctigenin derivatives against Dactylogyrus intermedius in goldfish.

PubMed

Hu, Yang; Liu, Lei; Liu, Guang-Lu; Tu, Xiao; Wang, Gao-Xue; Ling, Fei

2017-08-01

To control the parasitic disease of Dactylogyrus intermedius, a series of new arctigenin derivatives were designed, synthesized and tested in our study. The anthelmintic activity of most of the derivatives ranged from 1 to 10mg/L. Compared to traditional drug praziquantel (EC 50 =2.69mg/L), ether derivatives 2g and 2h exhibited slightly higher anti-parasitic activity, with the EC 50 values of 2.48 and 1.52mg/L, respectively. Furthermore, the arctigenin-imidazole hybrids 4a and 4b also removed D. intermedius effectively, with the EC 50 values of 2.13 and 2.07mg/L, respectively. The structure-activity relationship analysis indicated that four carbon atoms length of linker and imidazole substitute group could significantly increase the anthelmintic activity, and reduced the toxicity. Through the scanning electron microscope observation, compounds 4a and 4b caused the D. intermedius tegumental damage such as intensive wrinkles, holes and nodular structures. Overall, the structural optimization analysis of arctigenin suggested that 4a and 4b can be used for preventing and controlling Dactylogyrus infections and considered as promising lead compounds for the development of commercial drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cytotoxicity evaluation of gold nanoparticles on microalga Dunaliella salina in microplate test system

NASA Astrophysics Data System (ADS)

Chumakov, Daniil; Prilepskii, Artur; Dykman, Lev; Khlebtsov, Boris; Khlebtsov, Nikolai; Bogatyrev, Vladimir

2018-04-01

Gold nanoparticles are intensively studied in biomedicine. Assessment of their biocompatibility is highly important. Currently there is lack of evidence, concerning nanotoxicity of ultrasmall gold nanoparticles < 5 nm. Existing data are rather contradictory. The aim of that study was to evaluate the toxicity of 2 nm colloidal gold, using microalga Dunaliella salina. Cellular barriers of that microalga are very similar to animal cells so it might be considered as a valuable model for nanotoxicity testing. Chlorophyll content as a test-function was used. Spectrophotometric method for chlorophyll determination in vivo in suspensions of D.salina cultures was applied. Calculated EC50 48h value of ionic gold was 25.8 +/- 0.3 mg Au/L. EC50 value of phosphine-stabilized gold nanoclusters was 32.2 +/-1.1 mg Au/L. It was not possible to calculate EC50 for 15 nm citrate gold nanoparticles, as they were non-toxic at all concentrations tested. These results are confirmed by fluorescent -microscopic monitoring of the same probes. It was shown that 10-fold growth of phosphine-stabilized gold nanoparticles (from 2.3 +/- 0.9 nm to 21.1 +/- 7.5 nm) led to 7-fold decrease of their toxicity.

Application of ant colony optimization in development of models for prediction of anti-HIV-1 activity of HEPT derivatives.

PubMed

Zare-Shahabadi, Vali; Abbasitabar, Fatemeh

2010-09-01

Quantitative structure-activity relationship models were derived for 107 analogs of 1-[(2-hydroxyethoxy) methyl]-6-(phenylthio)thymine, a potent inhibitor of the HIV-1 reverse transcriptase. The activities of these compounds were investigated by means of multiple linear regression (MLR) technique. An ant colony optimization algorithm, called Memorized_ACS, was applied for selecting relevant descriptors and detecting outliers. This algorithm uses an external memory based upon knowledge incorporation from previous iterations. At first, the memory is empty, and then it is filled by running several ACS algorithms. In this respect, after each ACS run, the elite ant is stored in the memory and the process is continued to fill the memory. Here, pheromone updating is performed by all elite ants collected in the memory; this results in improvements in both exploration and exploitation behaviors of the ACS algorithm. The memory is then made empty and is filled again by performing several ACS algorithms using updated pheromone trails. This process is repeated for several iterations. At the end, the memory contains several top solutions for the problem. Number of appearance of each descriptor in the external memory is a good criterion for its importance. Finally, prediction is performed by the elitist ant, and interpretation is carried out by considering the importance of each descriptor. The best MLR model has a training error of 0.47 log (1/EC(50)) units (R(2) = 0.90) and a prediction error of 0.76 log (1/EC(50)) units (R(2) = 0.88). Copyright 2010 Wiley Periodicals, Inc.

Antifouling potential of the marine microalga Dunaliella salina.

PubMed

Gao, Min; Li, Fengchao; Su, Rongguo; Wang, Ke; Li, Xuzhao; Lu, Wei

2014-11-01

Marine organisms have usually been viewed as sources of environmentally friendly compounds with antifouling activity. We performed a series of operations to investigate the antifouling potential of the marine microalga Dunaliella salina. For the ethyl acetate crude extract, the antialgal activity was significant, and the EC50 value against Skeletonema costatum was 58.9 μg ml(-1). The isolated purified extract was tested for antifouling activity, the EC 50 value against S. costatum was 21.2 μg ml(-1), and the LC50 against Balanus amphitrite larvae was 18.8 μg ml(-1). Subsequently, both UHR-TOF-MS and GC-MS were used for the structural elucidation of the compounds, and a series of unsaturated and saturated 16- and 18-carbon fatty acids were detected. The data suggested that the fatty acid extracts from D. salina possess high antifouling activity, and could be used as substitutes for potent, toxic antifouling compounds.

Structure-activity relationships of flavonoids as natural inhibitors against E. coli β-glucuronidase.

PubMed

Weng, Zi-Miao; Wang, Ping; Ge, Guang-Bo; Dai, Zi-Ru; Wu, Da-Chang; Zou, Li-Wei; Dou, Tong-Yi; Zhang, Tong-Yan; Yang, Ling; Hou, Jie

2017-11-01

Bacterial β-glucuronidases play key roles in the deconjugation of a variety of endogenous and drug glucuronides, thus have been recognized as important targets to modulate the enterohepatic circulation of various glucuronides. In this study, more than 30 natural flavonoids were collected and their inhibitory effects against E. coli β-glucuronidase (EcGUS) were assayed. The results demonstrated that some flavonoids including scutellarein, luteolin, baicalein, quercetin and scutellarin displayed strong to moderate inhibitory effects against EcGUS, with the IC 50 values ranging from 5.76 μM to 29.64 μM, while isoflavones and dihydroflavones displayed weak inhibitory effects against EcGUS. Further investigation on inhibition kinetics revealed that scutellarein and luteolin functioned as potent competitive inhibitors against EcGUS-mediated PNPG hydrolysis, with the K i values less than 3.0 μM. Molecular docking simulations demonstrated that scutellarein and luteolin could be well-docked into the catalytic site of EcGUS, while the binding areas of these two natural inhibitors on EcGUS were highly overlapped with that of PNPG on EcGUS. Additionally, the structure-inhibition relationships of natural flavonoids against EcGUS are also summarized, which will be very helpful for the medicinal chemists to design and develop more potent flavonoid-type inhibitors against EcGUS. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nematicidal activity of furanocoumarins from parsley against Meloidogyne spp.

PubMed

Caboni, Pierluigi; Saba, Marco; Oplos, Chrisostomos; Aissani, Nadhem; Maxia, Andrea; Menkissoglu-Spiroudi, Urania; Casu, Laura; Ntalli, Nikoletta

2015-08-01

This report describes activity against Meloidogyne spp. and chemical characterisation of the essential oil and methanol extract of Petroselinum crispum aerial parts. The study was based on the hypothesis that P. crispum could be used as an intercrop and soil amendment in tomato culture for nematode control. The methanol extract and the essential oil exhibited significant nematicidal activity against M. incognita, M. hapla and M. arenaria, the first being the most sensitive species, with EC50 /72 h values of 140 ± 15 and 795 ± 125 mg L(-1) for the extract and oil respectively. The most abundant furanocoumarin compounds in the methanolic extract were xanthotoxin, psoralen, bergapten and oxypeucedanin; levels ranged from 1.77 to 46.04 mg kg(-1) wet weight. The EC50 /24 h values of xanthotoxol, psoralen and xanthotoxin against M. incognita were 68 ± 33, 147 ± 88 and 200 ± 21 mg L(-1) respectively. The addition of fresh parsley paste to soil reduced the number of M. incognita females and plant galls on tomato roots; EC50 values were 24.79 and 28.07 mg g(-1) respectively. Moreover, parsley paste enhanced tomato growth in a dose-response manner. Parsley exhibits promising nematicidal activity as an organic amendment and as a source of nematotoxic furanocoumarins. © 2014 Society of Chemical Industry.

Temporal variations in physico-chemical and microbiological characteristics of Mvudi river, South Africa.

PubMed

Edokpayi, Joshua N; Odiyo, John O; Msagati, Titus A M; Potgieter, Natasha

2015-04-14

Surface water has been a source of domestic water due to shortage of potable water in most rural areas. This study was carried out to evaluate the level of contamination of Mvudi River in South Africa by measuring turbidity, electrical conductivity (EC), pH, concentrations of nitrate, fluoride, chloride, and sulphate. E. coli and Enterococci were analysed using membrane filtration technique. Average pH, EC and Turbidity values were in the range of 7.2-7.7, 10.5-16.1 mS/m and 1.3-437.5 NTU, respectively. The mean concentrations of fluoride, chloride, nitrate and sulphate for both the wet and the dry seasons were 0.11 mg/L and 0.27 mg/L, 9.35 mg/L and 14.82 mg/L, 3.25 mg/L and 6.87 mg/L, 3.24 mg/L and 0.70 mg/L, respectively. E. coli and Enterococci counts for both the wet and the dry seasons were 4.81 × 103 (log = 3.68) and 5.22 × 103 (log = 3.72), 3.4 × 103 (log = 3.53) and 1.22 × 103 (log = 3.09), per 100 mL of water, respectively. The count of E. coli for both seasons did not vary significantly (p > 0.05) but Enterococci count varied significantly (p < 0.001). All the physico-chemical parameters obtained were within the recommended guidelines of the Department of Water Affairs and Forestry of South Africa and the World Health Organization for domestic and recreational water use for both seasons except turbidity and nitrates. The microbiological parameters exceeded the established guidelines. Mvudi River is contaminated with faecal organisms and should not be used for domestic purposes without proper treatment so as to mitigate the threat it poses to public health.

Agonist and antagonist modulation of [35S]-GTPγS binding in transfected CHO cells expressing the neurotensin receptor

PubMed Central

Hermans, Emmanuel; Geurts, Muriel; Maloteaux, Jean-Marie

1997-01-01

The functional interaction of the cloned rat neurotensin receptor with intracellular G-proteins was investigated by studying the binding of the radiolabelled guanylyl nucleotide analogue [35S]-GTPγS induced by neurotensin to membranes prepared from transfected Chinese hamster ovary (CHO) cells. The agonist-induced binding of [35S]-GTPγS was only detected in the presence of NaCl in the incubation buffer. However, it was also demonstrated that the binding of [3H]-neurotensin to its receptor was inhibited by NaCl. In the presence of 50 mM NaCl, the binding of the labelled nucleotide was about 2 fold increased by stimulation with saturating concentrations of neurotensin (EC50 value of 2.3±0.9 nM). The stimulation of [35S]-GTPγS binding by neurotensin was mimicked by the stable analogue of neurotensin, JMV-449 (EC50 value of 1.7±0.4 nM) and the neurotensin related peptide neuromedin N (EC50 value of 21±6 nM). The NT-induced [35S]-GTPγS binding was competitively inhibited by SR48692 (pA2 value of 9.55±0.28), a non-peptide neurotensin receptor antagonist. SR48692 alone had no effect on the specific binding of [35S]-GTPγS. The response to neurotensin was found to be inhibited by the aminosteroid U-73122, a putative inhibitor of phospholipase C-dependent processes, indicating that this drug may act at the G-protein level. Taken together, these results constitute the first characterization of the exchange of guanylyl nucleotides at the G-protein level that is induced by the neuropeptide neurotensin after binding to its receptor. PMID:9283723

Isocyanides Derived from α,α-Disubstituted Amino Acids: Synthesis and Antifouling Activity Assessment.

PubMed

Inoue, Yuki; Takashima, Shuhei; Nogata, Yasuyuki; Yoshimura, Erina; Chiba, Kazuhiro; Kitano, Yoshikazu

2018-03-01

Herein, we contribute to the development of environmentally friendly antifoulants by synthesizing eighteen isocyanides derived from α,α-disubstituted amino acids and evaluating their antifouling activity/toxicity against the cypris larvae of the Balanus amphitrite barnacle. Almost all isocyanides showed good antifouling activity without significant toxicity and exhibited EC 50 values of 0.07 - 7.30 μg/mL after 120-h exposure. The lowest EC 50 values were observed for valine-, methionine-, and phenylalanine-derived isocyanides, which achieved > 95% cypris larvae settlement inhibition at concentrations of less than 30 μg/mL without exhibiting significant toxicity. Thus, the prepared isocyanides should be useful for further research focused on the development of environmentally friendly antifouling agents. © 2018 Wiley-VHCA AG, Zurich, Switzerland.

Aquatic toxicity of four veterinary drugs commonly applied in fish farming and animal husbandry.

PubMed

Kołodziejska, Marta; Maszkowska, Joanna; Białk-Bielińska, Anna; Steudte, Stephanie; Kumirska, Jolanta; Stepnowski, Piotr; Stolte, Stefan

2013-08-01

Doramectin (DOR), metronidazole (MET), florfenicol (FLO), and oxytetracycline (OXT) are among the most widely used veterinary drugs in animal husbandry or in aquaculture. Contamination of the environment by these pharmaceuticals has given cause for concern in recent years. Even though their toxicity has been thoroughly analyzed, knowledge of their ecotoxicity is still limited. We investigated their aquatic toxicity using tests with marine bacteria (Vibrio fischeri), green algae (Scenedesmus vacuolatus), duckweed (Lemna minor) and crustaceans (Daphnia magna). All the ecotoxicological tests were supported by chemical analyses to confirm the exposure concentrations of the pharmaceuticals used in the toxicity experiments, since deviations from the nominal concentration can result in underestimation of biological effects. It was found that OXT and FLO have a stronger adverse effect on duckweed (EC50=3.26 and 2.96mgL(-1) respectively) and green algae (EC50=40.4 and 18.0mgL(-1)) than on bacteria (EC50=108 and 29.4mgL(-1)) and crustaceans (EC50=114 and 337mgL(-1)), whereas MET did not exhibit any adverse effect in the tested concentration range. For DOR a very low EC50 of 6.37×10(-5)mgL(-1) towards D. magna was determined, which is five orders of magnitude lower than values known for the toxic reference compound K2Cr2O7. Our data show the strong influence of certain veterinary drugs on aquatic organisms and contribute to a sound assessment of the environmental hazards posed by commonly used pharmaceuticals. Copyright © 2013. Published by Elsevier Ltd.

Antiplasmodial potential and quantification of aloin and aloe-emodin in Aloe vera collected from different climatic regions of India.

PubMed

Kumar, Sandeep; Yadav, Manila; Yadav, Amita; Rohilla, Pooja; Yadav, Jaya Parkash

2017-07-17

In this study, Aloe vera samples were collected from different climatic regions of India. Quantitative HPTLC (high performance thin layer chromatography) analysis of important anthraquinones aloin and aloe-emodin and antiplasmodial activity of crude aqueous extracts was done to estimate the effects of these constituents on antiplasmodial potential of the plant. HPTLC system equipped with a sample applicator Linomat V with CAMAG sample syringe, twin rough plate development chamber (20 x 10 cm), TLC Scanner 3 and integration software WINCATS 1.4.8 was used for analysis of aloin and aloe-emodin amount. The antiplasmodial activity of plant extracts was assessed against a chloroquine (CQ) sensitive strain of P. falciparum (MRC-2). Minimum Inhibitory Concentration (MIC) of aqueous extracts of selected samples was determined according to the World Health Organization (WHO) recommended method that was based on assessing the inhibition of schizont maturation in a 96-well microtitre plate. EC (effective concentration) values of different samples were observed to predict antiplasmodial potential of the plant in terms of their climatic zones. A maximum quantity of aloin and aloe-emodin i.e. 0.45 and 0.27 mg/g respectively was observed from the 12 samples of Aloe vera. The inhibited parasite growth with EC 50 values ranging from 0.289 to 1056 μg/ml. The antiplasmodial EC 50 value of positive control Chloroquine was observed 0.034 μg/ml and EC 50 values showed by aloin and aloe-emodin was 67 μg/ml and 22 μg/ml respectively. A positive correlation was reported between aloin and aloe-emodin. Antiplasmodial activity was increased with increase in the concentration of aloin and aloe-emodin. The quantity of aloin and aloe-emodin was decreased with rise in temperature hence it was negatively correlated with temperature. The extracts of Aloe vera collected from colder climatic regions showed good antiplasmodial activity and also showed the presence of higher amount of aloin and aloe-emodin in comparison to collected from warmer climatic sites. Study showed significant correlation between quantities of both the anthraquinones used as marker compounds and EC 50 values of the different Aloe vera extracts. Although, both the anthraquinones showed less antiplasmodial potential in comparison to crude extracts of different Aloe vera samples. Diverse climatic factors affect the quantity of tested compounds and antiplasmodial potential of the plant in different Aloe vera samples.

The discovery of novel diarylpyri(mi)dine derivatives with high level activity against a wide variety of HIV-1 strains as well as against HIV-2.

PubMed

Lu, Xueyi; Yang, Jiapei; Kang, Dongwei; Gao, Ping; Daelemans, Dirk; De Clercq, Erik; Pannecouque, Christophe; Zhan, Peng; Liu, Xinyong

2018-05-01

By means of structure-based molecular hybridization strategy, a series of novel diarylpyri(mi)dine derivatives targeting the entrance channel of HIV-1 reverse transcriptase (RT) were designed, synthesized and evaluated as potent non-nucleoside reverse transcriptase inhibitors (NNRTIs). Encouragingly, all the tested compounds showed good activities against wild-type (WT) HIV-1 (IIIB) with EC 50 in the range of 1.36 nM-29 nM, which is much better than those of nevirapine (NVP, EC 50  = 125.42 nM) and azidothymidine (AZT, EC 50  = 11.36 nM). Remarkably, these compounds also displayed effective activity against the most of the single and double-mutated HIV-1 strains with low EC 50 values, which is comparable to the control drugs. Besides, these compounds were also exhibited favorable enzymatic inhibitory activity. Moreover, preliminary structure-activity relationships (SARs) and molecular modeling study were investigated and discussed in detail. Unexpectedly, four diarylpyrimidines yielded moderate anti-HIV-2 activities. To our knowledge, this is rarely reported that diarylpyrimidine-based NNRTIs have potent activity against both HIV-1 and HIV-2 in cell culture. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mini-Review: Antifouling Natural Products from Marine Microorganisms and Their Synthetic Analogs

PubMed Central

Wu, Ze-Hong; Wang, Yu; Wang, Chang-Yun; Xu, Ying

2017-01-01

Biofouling causes huge economic loss and generates serious ecological issues worldwide. Marine coatings incorporated with antifouling (AF) compounds are the most common practices to prevent biofouling. With a ban of organotins and an increase in the restrictions regarding the use of other AF alternatives, exploring effective and environmentally friendly AF compounds has become an urgent demand for marine coating industries. Marine microorganisms, which have the largest biodiversity, represent a rich and important source of bioactive compounds and have many medical and industrial applications. This review summarizes 89 natural products from marine microorganisms and 13 of their synthetic analogs with AF EC50 values ≤ 25 μg/mL from 1995 (the first report about marine microorganism-derived AF compounds) to April 2017. Some compounds with the EC50 values < 5 μg/mL and LC50/EC50 ratios > 50 are highlighted as potential AF compounds, and the preliminary analysis of structure-relationship (SAR) of these compounds is also discussed briefly. In the last part, current challenges and future research perspectives are proposed based on opinions from many previous reviews. To provide clear guidance for the readers, the AF compounds from microorganisms and their synthetic analogs in this review are categorized into ten types, including fatty acids, lactones, terpenes, steroids, benzenoids, phenyl ethers, polyketides, alkaloids, nucleosides and peptides. In addition to the major AF compounds which targets macro-foulers, this review also includes compounds with antibiofilm activity since micro-foulers also contribute significantly to the biofouling communities. PMID:28846626

Mini-Review: Antifouling Natural Products from Marine Microorganisms and Their Synthetic Analogs.

PubMed

Wang, Kai-Ling; Wu, Ze-Hong; Wang, Yu; Wang, Chang-Yun; Xu, Ying

2017-08-28

Biofouling causes huge economic loss and generates serious ecological issues worldwide. Marine coatings incorporated with antifouling (AF) compounds are the most common practices to prevent biofouling. With a ban of organotins and an increase in the restrictions regarding the use of other AF alternatives, exploring effective and environmentally friendly AF compounds has become an urgent demand for marine coating industries. Marine microorganisms, which have the largest biodiversity, represent a rich and important source of bioactive compounds and have many medical and industrial applications. This review summarizes 89 natural products from marine microorganisms and 13 of their synthetic analogs with AF EC 50 values ≤ 25 μg/mL from 1995 (the first report about marine microorganism-derived AF compounds) to April 2017. Some compounds with the EC 50 values < 5 μg/mL and LC 50 /EC 50 ratios > 50 are highlighted as potential AF compounds, and the preliminary analysis of structure-relationship (SAR) of these compounds is also discussed briefly. In the last part, current challenges and future research perspectives are proposed based on opinions from many previous reviews. To provide clear guidance for the readers, the AF compounds from microorganisms and their synthetic analogs in this review are categorized into ten types, including fatty acids, lactones, terpenes, steroids, benzenoids, phenyl ethers, polyketides, alkaloids, nucleosides and peptides. In addition to the major AF compounds which targets macro-foulers, this review also includes compounds with antibiofilm activity since micro-foulers also contribute significantly to the biofouling communities.

Acute toxicity of heavy metals to acetate-utilizing mixed cultures of sulfate-reducing bacteria: EC100 and EC50.

PubMed

Utgikar, V P; Chen, B Y; Chaudhary, N; Tabak, H H; Haines, J R; Govind, R

2001-12-01

Acid mine drainage from abandoned mines and acid mine pit lakes is an important environmental concern and usually contains appreciable concentrations of heavy metals. Because sulfate-reducing bacteria (SRB) are involved in the treatment of acid mine drainage, knowledge of acute metal toxicity levels for SRB is essential for the proper functioning of the treatment system for acid mine drainage. Quantification of heavy metal toxicity to mixed cultures of SRB is complicated by the confounding effects of metal hydroxide and sulfide precipitation, biosorption, and complexation with the constituents of the reaction matrix. The objective of this paper was to demonstrate that measurements of dissolved metal concentrations could be used to determine the toxicity parameters for mixed cultures of sulfate-reducing bacteria. The effective concentration, 100% (EC100), the lowest initial dissolved metal concentrations at which no sulfate reduction is observed, and the effective concentration, 50% (EC50), the initial dissolved metal concentrations resulting in a 50% decrease in sulfate reduction, for copper and zinc were determined in the present study by means of nondestructive, rapid physical and chemical analytical techniques. The reaction medium used in the experiments was designed specifically (in terms of pH and chemical composition) to provide the nutrients necessary for the sulfidogenic activity of the SRB and to preclude chemical precipitation of the metals under investigation. The toxicity-mitigating effects of biosorption of dissolved metals were also quantified. Anaerobic Hungate tubes were set up (at least in triplicate) and monitored for sulfate-reduction activity. The onset of SRB activity was detected by the blackening of the reaction mixture because of formation of insoluble ferrous sulfide. The EC100 values were found to be 12 mg/L for copper and 20 mg/L for zinc. The dissolved metal concentration measurements were effective as the indicators of the effect of the heavy metals at concentrations below EC100. The 7-d EC50 values obtained from the difference between the dissolved metal concentrations for the control tubes (tubes not containing copper or zinc) and tubes containing metals were found to be 10.5 mg/L for copper and 16.5 mg/L for zinc. Measurements of the turbidity and pH, bacterial population estimations by means of a most-probable number technique, and metal recovery in the sulfide precipitate were found to have only a limited applicability in these determinations.

Quantifying sources of elemental carbon over the Guanzhong Basin of China: A consistent network of measurements and WRF-Chem modeling.

PubMed

Li, Nan; He, Qingyang; Tie, Xuexi; Cao, Junji; Liu, Suixin; Wang, Qiyuan; Li, Guohui; Huang, Rujin; Zhang, Qiang

2016-07-01

We conducted a year-long WRF-Chem (Weather Research and Forecasting Chemical) model simulation of elemental carbon (EC) aerosol and compared the modeling results to the surface EC measurements in the Guanzhong (GZ) Basin of China. The main goals of this study were to quantify the individual contributions of different EC sources to EC pollution, and to find the major cause of the EC pollution in this region. The EC measurements were simultaneously conducted at 10 urban, rural, and background sites over the GZ Basin from May 2013 to April 2014, and provided a good base against which to evaluate model simulation. The model evaluation showed that the calculated annual mean EC concentration was 5.1 μgC m(-3), which was consistent with the observed value of 5.3 μgC m(-3). Moreover, the model result also reproduced the magnitude of measured EC in all seasons (regression slope = 0.98-1.03), as well as the spatial and temporal variations (r = 0.55-0.78). We conducted several sensitivity studies to quantify the individual contributions of EC sources to EC pollution. The sensitivity simulations showed that the local and outside sources contributed about 60% and 40% to the annual mean EC concentration, respectively, implying that local sources were the major EC pollution contributors in the GZ Basin. Among the local sources, residential sources contributed the most, followed by industry and transportation sources. A further analysis suggested that a 50% reduction of industry or transportation emissions only caused a 6% decrease in the annual mean EC concentration, while a 50% reduction of residential emissions reduced the winter surface EC concentration by up to 25%. In respect to the serious air pollution problems (including EC pollution) in the GZ Basin, our findings can provide an insightful view on local air pollution control strategies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Vasodilatory Effects of Combined Traditional Chinese Medicinal Herbs in Optimized Ratio.

PubMed

Loh, Yean Chun; Tan, Chu Shan; Ch'ng, Yung Sing; Ahmad, Mariam; Asmawi, Mohd Zaini; Yam, Mun Fei

2017-03-01

Recently, a new syndromic disease combination theory of traditional Chinese medicine (TCM) for hypertensive treatment has been introduced. In the wake of this new concept, a new science-based TCM formula that counteracts various syndromes is needed. The objective of this study was to develop such a formula. Five of the most clinically prescribed TCM herbs that work on different syndromes, namely Gastrodia elata, Uncaria rhynchophylla, Pueraria thomsonii, Panax notoginseng, and Alisma orientale, were selected for this study. The fingerprints of these five herbs were analyzed by tri-step Fourier transform infrared spectroscopy. Three different solvents, 95% ethanol, 50% ethanol, and distilled water, were used for the maceration of the herbs and their vasodilatory effects were studied using in vitro precontracted aortic ring model. Among these, the 50% ethanolic extracts of G. elata (GE50) and A. orientale (AO50), and 95% ethanolic extracts of U. rhynchophylla (UR95), P. thomsonii (PT95), and P. notoginseng (PN95) were found to be the most effective for eliciting vasodilation. Thus, these five extracts were used for orthogonal stimulus-response compatibility group studies by using L 25 (5 5 ) formula. The best combination ratio for GE50, UR95, PT95, PN95, and AO50, which was assigned as Formula 1 (F1), was found at EC 0 , EC 25 , EC 20 , EC 20 , and EC 10 , respectively. The vasodilatory effect of the extracts prepared from different extraction methods using F1 ratio was also studied. From the results, the EC 50 and R max of total 50% ethanolic extract of five herbs using F1 ratio (F1-2) were 0.028 ± 0.005 mg/mL and 101.71% ± 3.64%, with better values than F1 (0.104 ± 0.014 mg/mL and 97.80% ± 3.12%, respectively). In conclusion, the optimum ratio and appropriate extraction method (F1-2) for the new TCM formula were revealed.

Discovery of novel DAPY-IAS hybrid derivatives as potential HIV-1 inhibitors using molecular hybridization based on crystallographic overlays.

PubMed

Huang, Boshi; Wang, Xueshun; Liu, Xinhao; Chen, Zihui; Li, Wanzhuo; Sun, Songkai; Liu, Huiqing; Daelemans, Dirk; De Clercq, Erik; Pannecouque, Christophe; Zhan, Peng; Liu, Xinyong

2017-08-15

Crystallographic overlap studies and pharmacophoric analysis indicated that diarylpyrimidine (DAPY)-based HIV-1 NNRTIs showed a similar binding mode and pharmacophoric features as indolylarylsulfones (IASs), another class of potent NNRTIs. Thus, a novel series of DAPY-IAS hybrid derivatives were identified as newer NNRTIs using structure-based molecular hybridization. Some target compounds exhibited moderate activities against HIV-1 IIIB strain, among which the two most potent inhibitors possessed EC 50 values of 1.48μM and 1.61μM, respectively. They were much potent than the reference drug ddI (EC 50 =76.0μM) and comparable to 3TC (EC 50 =2.54μM). Compound 7a also exhibited the favorable selectivity index (SI=80). Preliminary structure-activity relationships (SARs), structure-cytotoxicity relationships, molecular modeling studies, and in silico calculation of physicochemical properties of these new inhibitors were also discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Simultaneous determination of ethyl carbamate and urea in Korean rice wine by ultra-performance liquid chromatography coupled with mass spectrometric detection.

PubMed

Lee, Gyeong-Hweon; Bang, Dae-Young; Lim, Jung-Hoon; Yoon, Seok-Min; Yea, Myeong-Jai; Chi, Young-Min

2017-10-15

In this study, a rapid method for simultaneous detection of ethyl carbamate (EC) and urea in Korean rice wine was developed. To achieve quantitative analysis of EC and urea, the conditions for Ultra-performance liquid chromatography (UPLC) separation and atmospheric-pressure chemical ionization tandem mass spectrometry (APCI-MS/MS) detection were first optimized. Under the established conditions, the detection limit, relative standard deviation and linear range were 2.83μg/L, 3.75-5.96%, and 0.01-10.0mg/L, respectively, for urea; the corresponding values were 0.17μg/L, 1.06-4.01%, and 1.0-50.0μg/L, respectively, for EC. The correlation between the contents of EC and its precursor urea was determined under specific pH (3.5 and 4.5) and temperature (4, 25, and 50°C) conditions using the developed method. As a result, EC content was increased with greater temperature and lower pH. In Korean rice wine, urea was detected 0.19-1.37mg/L and EC was detected 2.0-7.7μg/L. The method developed in this study, which has the advantages of simplified sample preparation, low detection limits, and good selectivity, was successfully applied for the rapid analysis of EC and urea. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of toxicity and biodegradability of choline chloride based deep eutectic solvents.

PubMed

Radošević, Kristina; Bubalo, Marina Cvjetko; Srček, Višnje Gaurina; Grgas, Dijana; Dragičević, Tibela Landeka; Redovniković, Ivana Radojčić

2015-02-01

Deep eutectic solvents (DESs) have been dramatically expanding in popularity as a new generation of environmentally friendly solvents with possible applications in various industrial fields, but their ecological footprint has not yet been thoroughly investigated. In the present study, three choline chloride-based DESs with glucose, glycerol and oxalic acid as hydrogen bond donors were evaluated for in vitro toxicity using fish and human cell line, phytotoxicity using wheat and biodegradability using wastewater microorganisms through closed bottle test. Obtained in vitro toxicity data on cell lines indicate that choline chloride: glucose and choline chloride:glycerol possess low cytotoxicity (EC50>10 mM for both cell lines) while choline chloride:oxalic acid possess moderate cytotoxicity (EC50 value 1.64 mM and 4.19 mM for fish and human cell line, respectively). Results on phytotoxicity imply that tested DESs are non-toxic with seed germination EC50 values higher than 5000 mg L(-1). All tested DESs were classified as'readily biodegradable' based on their high levels of mineralization (68-96%). These findings indicate that DESs have a green profile and a good prospect for a wider use in the field of green technologies. Copyright © 2014 Elsevier Inc. All rights reserved.

[Study of combined effects of DES and EV on the proliferation of MCF-7 cells by two experimental designs].

PubMed

Liu, Qian; Lei, Bing-Li; An, Jing; Shang, Yu; Zhong, Yu-Fang; Kang, Jia; Wen, Yu

2013-08-01

The single toxicity of diethylstilbestrol (DES) and beta-estradiol 17-valerate (EV) and the joint toxicity of their binary mixtures in equiconcentration to the proliferation of MCF-7 cells were investigated, respectively. Additive index (AI) method was adopted to evaluate the joint toxicity effect. At the same time, 3 x 3 factorial experimental design was used to verify the joint toxiciy types derived from equiconcentration of DES and EV. The results show that the EC50 values of single EV and DES for 24, 48 and 72 h are 6.02, 0.40 and 0.33 nmol x L(-1) and 5.90, 6.98 and 2.90 nmol x L(-1), respectively. The EC50 values of the binary mixtures of DES and EV for 24, 48 and 72 h are 2.33, 0.71 and 0.39 nmol x L(-1). The binary joint effects of DES and EV for 24 h were synergistic, and the joint effects of DES and EV for 48 and 72 h were antagonistic. But synergistic and antagonistic effects are not strong; their values can be found close to the values of additive effects. Factorial experiment results show that combined effects of DES and EV to proliferation of MCF-7 cells for 24, 48 and 72 h three exposure periods are additive effect types. The consistent joint combined effect types can be drawn from both factorial experimental design and equiconcentration ratio of DES and EV to the proliferation of MCF-7 cells. However, the factorial experimental design is simpler and more convenient, and can avoid unnecessary mistakes due to the derivation of EC50 values.

Comparison of human immunodeficiency virus assays in window phase and elite controller samples: viral load distribution and implications for transmission risk

PubMed Central

Vermeulen, Marion; Coleman, Charl; Mitchel, Josephine; Reddy, Ravi; van Drimmelen, Harry; Fickett, Tracy; Busch, Michael; Lelie, Nico

2016-01-01

BACKGROUND After 3 years of individual-donation nucleic acid test (ID-NAT) screening by the South African National Blood Service (SANBS), a repository of 73 human immunodeficiency virus antibody (anti-HIV)-negative window period (WP)-yield samples and 28 anti-HIV–positive, HIV-RNA–negative elite controllers (ECs) became available for comparison of a p24 antigen (p24 Ag) assay (Innogenetics), two viral load assays (Siemens branch DNA [bDNA] 3.0 and Abbott real-time polymerase chain reaction [RT-PCR]), and three triplex NAT assays (Novartis Diagnostics Ultrio and Ultrio-Plus and Roche TaqScreen) by replicate testing of dilutions. STUDY DESIGN AND METHODS Viral loads were assessed by bDNA and RT-PCR assays and if below 100 copies (cps)/mL, by Ultrio limiting dilution probit analysis. The probability of virus transmission by WP and EC donations was estimated for different levels of the 50% minimum infectious dose (ID50) using Poisson distribution statistics. RESULTS The equal distribution of WP donations plotted by log HIV-RNA levels indicated a random appearance of donors in the ramp-up phase. The HIV p24 Ag assay detected 45% of WP samples and the cutoff crossing point was estimated at 8140 (bDNA)/ 22,710 (RT-PCR) cps/mL. On replicate retesting of 40 HIV p24 Ag–negative ID-NAT WP-yield samples Ultrio minipool (MP)8, Ultrio-Plus MP8, and TaqScreen MP6 detected 79, 81, and 78%, respectively. Modeling with an estimated ID50 of 31.6 virions/RBC indicated that 15% of p24 Ag–negative ID-NAT WP-yield donations would have transmitted HIV if MP6–8 NAT had been used. Only 2% of RBC transfusions from ECs are estimated to be infectious with a worst-case ID50 estimate of 316 virions. CONCLUSION Our analysis of viremia and infectivity of WP and EC donations enables comparison of the efficacy of NAT options in preventing HIV transmission risk. PMID:23445273

Comparison of human immunodeficiency virus assays in window phase and elite controller samples: viral load distribution and implications for transmission risk.

PubMed

Vermeulen, Marion; Coleman, Charl; Mitchel, Josephine; Reddy, Ravi; van Drimmelen, Harry; Fickett, Tracy; Busch, Michael; Lelie, Nico

2013-10-01

After 3 years of individual-donation nucleic acid test (ID-NAT) screening by the South African National Blood Service (SANBS), a repository of 73 human immunodeficiency virus antibody (anti-HIV)-negative window period (WP)-yield samples and 28 anti-HIV-positive, HIV-RNA-negative elite controllers (ECs) became available for comparison of a p24 antigen (p24 Ag) assay (Innogenetics), two viral load assays (Siemens branch DNA [bDNA] 3.0 and Abbott real-time polymerase chain reaction [RT-PCR]), and three triplex NAT assays (Novartis Diagnostics Ultrio and Ultrio-Plus and Roche TaqScreen) by replicate testing of dilutions. Viral loads were assessed by bDNA and RT-PCR assays and if below 100 copies (cps)/mL, by Ultrio limiting dilution probit analysis. The probability of virus transmission by WP and EC donations was estimated for different levels of the 50% minimum infectious dose (ID50 ) using Poisson distribution statistics. The equal distribution of WP donations plotted by log HIV-RNA levels indicated a random appearance of donors in the ramp-up phase. The HIV p24 Ag assay detected 45% of WP samples and the cutoff crossing point was estimated at 8140 (bDNA)/22,710 (RT-PCR) cps/mL. On replicate retesting of 40 HIV p24 Ag-negative ID-NAT WP-yield samples Ultrio minipool (MP)8, Ultrio-Plus MP8, and TaqScreen MP6 detected 79, 81, and 78%, respectively. Modeling with an estimated ID50 of 31.6 virions/RBC indicated that 15% of p24 Ag-negative ID-NAT WP-yield donations would have transmitted HIV if MP6-8 NAT had been used. Only 2% of RBC transfusions from ECs are estimated to be infectious with a worst-case ID50 estimate of 316 virions. Our analysis of viremia and infectivity of WP and EC donations enables comparison of the efficacy of NAT options in preventing HIV transmission risk. © 2013 American Association of Blood Banks.

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

PubMed

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 attributed to differences in molarity or valency. For chrome salts the difference in EC50 values may be explained by different valencies (VI vs. III), but not by molarity. In general, metal salts were classified as weaker sensitizers than was indicated from in vivo LLNA EC3 and NOEL data. Our in vitro results show that metals are problematic chemicals to test, in line with the limited number of standardized human and animal studies, which are not currently considered adequate to predict systemic hypersensitivity or autoimmunity, and despite clinical experience, which clearly shows that many metals are indeed a risk to human health. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Linear solvation energy relationships for toxicity of selected organic chemicals to Daphnia pulex and Daphnia magna

USGS Publications Warehouse

Passino, Dora R.M.; Hickey, James P.; Frank, Anthony M.

1988-01-01

In the Laurentian Great Lakes, more than 300 contaminants have been identified in fish, other biota, water, and sediment. Current hazard assessment of these chemicals by the National Fisheries Research Center-Great Lakes is based on their toxicity, occurrence in the environment, and source. Although scientists at the Center have tested over 70 chemicals with the crustacean Daphnia pulex, the number of experimental data needed to screen the huge array of chemicals in the Great Lakes exceeds the practical capabilities of conducting bioassays. This limitation can be partly circumvented, however, by using mathematical models based on quantitative structure-activity relationships (QSAR) to provide rapid, inexpensive estimates of toxicity. Many properties of chemicals, including toxicity, bioaccumulation and water solubility are well correlated and can be predicted by equations of the generalized linear solvation energy relationships (LSER). The equation we used to model solute toxicity is Toxicity = constant + mVI/100 + s (π* + dδ) + bβm + aαm where VI = intrinsic (Van der Waals) molar volume; π* = molecular dipolarity/polarizability; δ = polarizability 'correction term'; βm = solute hydrogen bond acceptor basicity; and αm = solute hydrogen bond donor acidity. The subscript m designates solute monomer values for α and β. We applied the LSER model to 48-h acute toxicity data (measured as immobilization) for six classes of chemicals detected in Great Lakes fish. The following regression was obtained for Daphnia pulex (concentration = μM): log EC50 = 4.86 - 4.35 VI/100; N = 38, r2 = 0.867, sd = 0.403 We also used the LSER modeling approach to analyze to a large published data set of 24-h acute toxicity for Daphnia magna; the following regression resulted, for eight classes of compounds (concentration = mM): log EC50 = 3.88 - 4.52 VI/100 - 1.62 π* + 1.66 βm - 0.916 αm; N = 62, r2 = 0.859, sd = 0.375 In addition we developed computer software that identifies chemical structures, estimates the LSER parameters, and predicts toxicity. The LSER models promise to be effective in differentiating between reactive and nonreactive toxicity behavior where other models have failed. Contaminants with reactive behavior are generally the most toxic and rank highest in hazard assessment of environmental chemicals.

EFFECTIVE CONCENTRATIONS OF 6 CONTAMINANTS TO LEMMA MINOR, PIMEPHALES PROMELA, DAPHNIA MAGNA, AND CERIODAPHNIA DUBIA

EPA Science Inventory

The research presented here resulted in EC50 and LOEC values for the contaminants copper, cadmium, diazinon, atrazine, and cyanide to the species Lemna Minor, Pimephales promelas, Daphnia magna, and Ceriodaphnia dubia. Observed values were used as benchmarks for assessing the se...

Predictive spatial modelling for mapping soil salinity at continental scale

NASA Astrophysics Data System (ADS)

Bui, Elisabeth; Wilford, John; de Caritat, Patrice

2017-04-01

Soil salinity is a serious limitation to agriculture and one of the main causes of land degradation. Soil is considered saline if its electrical conductivity (EC) is > 4 dS/m. Maps of saline soil distribution are essential for appropriate land development. Previous attempts to map soil salinity over extensive areas have relied on satellite imagery, aerial electromagnetic (EM) and/or proximally sensed EM data; other environmental (climate, topographic, geologic or soil) datasets are generally not used. Having successfully modelled and mapped calcium carbonate distribution over the 0-80 cm depth in Australian soils using machine learning with point samples from the National Geochemical Survey of Australia (NGSA), we took a similar approach to map soil salinity at 90-m resolution over the continent. The input data were the EC1:5 measurements on the < 2mm fraction at 1315 georeferenced points across the continent at two depth intervals (TOS, 0-10 cm, and BOS, 60-80 cm) (see http://www.ga.gov.au/energy/projects/national-geochemical-survey/atlas.html) were log-transformed and combined with values for climate, elevation and terrain attributes, soil and lithology classes, geophysics, and MODIS vegetation indices extracted at the same locations which were used as predictors in decision tree models. The machine learning software 'Cubist' (www.rulequest.com) was used as the inference engine for the modelling, a 90:10 training:test set data split was used to validate results, and 100 randomly sampled trees were built using the training data. The results were good with an average internal correlation (r) of 0.88 between predicted and measured logEC1:5 (training data), an average external correlation of 0.48 (test subset), and a Lin's concordance correlation coefficient (which evaluates the 1:1 fit) of 0.61. Therefore, the rules derived were mapped and the mean prediction for each 90-m pixel was used for the final logEC1:5 map. This is the most detailed picture of soil salinity over Australia since the 2001 National Land and Water Resources Audit and is generally consistent with it. Our map will be useful as a baseline salinity map circa 2008, when the NGSA samples were collected, for future State of the Environment reports.

Allosteric modulation of semicarbazide-sensitive amine oxidase activities in vitro by imidazoline receptor ligands

PubMed Central

Holt, Andrew; Wieland, Barbara; Baker, Glen B

2004-01-01

Evidence indicates that imidazoline I2 binding sites (I2BSs) are present on monoamine oxidase (MAO) and on soluble (plasma) semicarbazide-sensitive amine oxidase enzymes. The binding site on MAO has been described as a modulatory site, although no effects on activity are thought to have been observed as a result of ligands binding to these sites. We examined the effects in vitro of several imidazoline binding site ligands on activities of bovine plasma amine oxidase (BPAO) and porcine kidney diamine oxidase (PKDAO) in a spectrophotometric protocol. While both enzymes were inhibited at high concentrations of all ligands, clonidine, cirazoline and oxymetazoline were seen, at lower concentrations, to increase activity of BPAO versus benzylamine, but not of PKDAO versus putrescine. This effect was substrate dependent, with mixed or biphasic inhibition of spermidine, methylamine, p-tyramine and β-phenylethylamine oxidation observed at cirazoline concentrations that increased benzylamine oxidation. With benzylamine as substrate, clonidine decreased KM (EC50 8.82 μM, Emax 75.1% of control) and increased Vmax (EC50 164.6 μM, Emax 154.1% of control). Cirazoline decreased Vmax (EC50 2.15 μM, Emax 91.4% of control), then decreased KM (EC50 5.63 μM, Emax 42.6% of control) and increased Vmax (EC50 49.0 μM, Emax 114.4% of decreased Vmax value). Data for clonidine fitted a mathematical model for two-site nonessential activation plus linear intersecting noncompetitive inhibition. Data for cirazoline were consistent with involvement of a fourth site. These results reveal an ability of imidazoline ligands to modulate BPAO kinetics allosterically. The derived mechanism may have functional significance with respect to modulation of MAO by I2BS ligands. PMID:15451775

Antioxidant properties of Australian canola meal protein hydrolysates.

PubMed

Alashi, Adeola M; Blanchard, Christopher L; Mailer, Rodney J; Agboola, Samson O; Mawson, A John; He, Rong; Girgih, Abraham; Aluko, Rotimi E

2014-03-01

Antioxidant activities of canola protein hydrolysates (CPHs) and peptide fractions prepared using five proteases and ultrafiltration membranes (1, 3, 5, and 10kDa) were investigated. CPHs had similar and adequate quantities of essential amino acids. The effective concentration that scavenged 50% (EC50) of the ABTS(+) was greatest for the <1kDa pancreatin fraction at 10.1μg/ml. CPHs and peptide fractions scavenged DPPH(+) with most of the EC50 values being <1.0mg/ml. Scavenging of superoxide radical was generally weak, except for the <1kDa pepsin peptide fraction that had a value of 51%. All CPHs inhibited linoleic acid oxidation with greater efficiency observed for pepsin hydrolysates. The oxygen radical absorbance capacity of Alcalase, chymotrypsin and pepsin hydrolysates was found to be better than that of glutathione (GSH) (p<0.05). These results show that CPHs have the potential to be used as bioactive ingredients in the formulation of functional foods against oxidative stress. Copyright © 2013 Elsevier Ltd. All rights reserved.

Phytochemical screening, cytotoxicity and antiviral activity of hexane fraction of Phaleria macrocarpa fruits

NASA Astrophysics Data System (ADS)

Ismaeel, Mahmud Yusef Yusef; Yaacob, Wan Ahmad; Tahir, Mariya Mohd.; Ibrahim, Nazlina

2015-09-01

Phaleria macrocarpa fruits have been widely used in the traditional medicine for the treatment of several infections. The current study was done to determine the phytochemical content, cytotoxicity and antiviral activity of the hexane fraction (HF) of P. macrocarpa fruits. In the hexane fraction of P. macarocarpa fruits, phytochemical screening showed the presence of terpenoids whereas saponins, alkaloids, tannins and anthraquinones were not present. Evaluation on Vero cell lines by using MTT assay showed that the 50% cytotoxic concentration (CC50) value was 0.48 mg/mL indicating that the fraction is not cytotoxic. Antiviral properties of the plant extracts were determined by plaque reduction assay. The effective concentration (EC50) was 0.18 mg/mL. Whereas the selective index (SI = CC50/EC50) of hexane fraction is 2.6 indicating low to moderate potential as antiviral agent.

In vitro antiviral activity of aqueous extract of Phaleria macrocarpa fruit against herpes simplex virus type 1

NASA Astrophysics Data System (ADS)

Ismaeel, Mahmud Yusef Yusef; Dyari, Herryawan Ryadi Eziwar; Yaacob, Wan Ahmad; Ibrahim, Nazlina

2018-04-01

Phaleria macrocarpa fruits have been used as herbal medicine for several diseases. This study aims to determine the cytotoxicity and antiviral activity of aqueous extract of P. macrocarpa fruit (AEPMF). Phytochemical analysis showed the presence of steroids, tannins, flavones aglycones, saponins, terpenoids and alkaloids. AEPMF was found to contain protein with the concentration of 740 µg/mL. The cytotoxicity towards Vero cell was evaluated using MTT assay with 50% cytotoxic concentration (CC50) value of AEPMF 5 mg/mL. The finding indicates that AEPMF is safe and not toxic towards Vero cells. Screening by plaque reduction assay showed that AEPMF have antiviral activity against herpes simplex virus type 1 (HSV-1) with effective concentration (EC50) was 0.28 mg/mL. The selective index (SI=CC50/EC50) of AEPMF is 17.9 indicating AEPMF have potential for further evaluation in antiviral activity.

Interaction of Cd and Zn toxicity for Folsomia candida Willem (Collembola: Isotomidae) in relation to bioavailability in soil

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Gestel, C.A.M.; Hensbergen, P.J.

1997-06-01

The use of toxicity tests in which each chemical is tested separately is inadequate for assessing the potential risk of complex mixtures of chemicals for soil ecosystems. In the present study, the effects of Cd and Zn, alone or in combination, on the survival, growth, and reproduction of the collembolan Folsomia candida were determined after 2, 4, and 6 weeks of exposure in an artificial soil. The water solubility of Cd in the soil was significantly increased by the presence of Zn, whereas Cd did not affect the water solubility of Zn. In spite of this, uptake of Cd ormore » Zn in the animals was not affected by the presence of the other metal, suggesting that water solubility does not determine the uptake of these metals in F. candida. For both Cd and Zn, reproduction was the most sensitive parameter, with 50% effective concentration (EC50) values of 51 and 683 {micro}g/g dry soil, respectively, after 6 weeks. These values corresponded with internal concentrations of 44 {micro}g Cd/g and 14 {micro}g Zn/g dry soil, respectively. Although a proper comparison of the effects of mixtures of the metals with the effects of the individual metals was sometimes hampered by the nonsimilarity of dose-response relationships, it may be concluded that the effects of the mixture of Cd and Zn on the growth of F. candida are antagonistic (EC50 significantly greater than 1.0 toxic unit), while the effects on reproduction are additive (EC50 = 1.0 toxic unit). Similar conclusions could be drawn for EC50s expressed on the basis of total and water-soluble soil concentrations as well as on the basis of internal concentrations in animals. Analysis of the combined effects of Cd and Zn at the 10% effective concentration level did not change these conclusions.« less

Effect of tachykinins in small human airways.

PubMed

Frossard, N; Barnes, J

1991-07-01

We have compared the contractile responses of substance P (SP) and neurokinin A (NKA) to that of the non degradable muscarinic agonist, carbachol, in small and large human airways in vitro. We have also investigated the effects of the neutral endopeptidase (NEP) inhibitor, thiorphan (100 microM) on these responses. NKA contracted large and small airways to a different extent (56% vs 92% of carbachol maximal contraction, respectively). NKA was significantly less potent in large vs small bronchi (EC50 = 150 +/- 15 vs 12 +/- 5 nM respectively, p less than 0.05). SP had a lower contractile effect in large (26% carbachol maximum) and small airways (59%) with EC50 values higher than 0.5 microM. The enkephalinase inhibitor thiorphan shifted the concentration-response curve to NKA to the left in large (EC50 = 35.2 +/- 8.2 nM) and small bronchi (EC50 = 2.8 +/- 1.3 nM, p less than 0.02). This shift was associated with an increase in the maximal contraction to NKA (75% in large vs 123% in small bronchi). The amplitude of contraction to SP was also potentiated in large (45%) and in smaller bronchi (101%). In conclusion, we have demonstrated that NKA has a significantly greater constrictor effect than a cholinergic agent in more peripheral human airways in vitro. This suggests that non cholinergic constrictor pathways are more likely to be important in more peripheral airways.

Synthesis of novel quinoline-based 4,5-dihydro-1H-pyrazoles as potential anticancer, antifungal, antibacterial and antiprotozoal agents.

PubMed

Ramírez-Prada, Jonathan; Robledo, Sara M; Vélez, Iván D; Crespo, María Del Pilar; Quiroga, Jairo; Abonia, Rodrigo; Montoya, Alba; Svetaz, Laura; Zacchino, Susana; Insuasty, Braulio

2017-05-05

A new series of N-substituted 2-pyrazolines 9a-f, 10a-f, 11a-f, 12a-f and 13a-f were obtained from the cyclocondensation reaction of [(7-chloroquinolin-4-yl)amino]chalcones 8a-f with hydrazine hydrate and its derivatives. Fourteen of the synthesized compounds including the starting chalcones were selected by US National Cancer Institute (NCI) for testing their anticancer activity against 60 different human cancer cell lines, with the most important GI 50 values ranging from 0.28 to 11.7 μM (0.13-6.05 μg/mL) and LC 50 values ranging from 2.6 to > 100 μM (1.2 to > 51.7 μg/mL), for chalcones 8a,d and pyrazolines 10c,d. All compounds were assessed for antibacterial activity against wild type and multidrug resistant gram negative and gram positive bacteria, with MIC values ranging from 31.25 to 500 μg/mL. Additionally, the novel compounds were tested for antifungal and antiparasitic properties. Although these compounds showed mild activity against Candida albicans, chalcones 8a and 8e showed high activity against Cryptococcus neoformans with MIC 50  = 7.8 μg/mL. For anti-Plasmodium falciparum activity the 2-pyrazoline 11b was the most active with EC 50  = 5.54 μg/mL. Regarding the activity against Trypanosoma cruzi, compound 10a was highly active with EC 50  = 0.70 μg/mL. Chalcone 8a had good activity against Leishmania panamensis amastigotes with EC 50  = 0.79 μg/mL. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The relevance of the slope for concentration-effect relations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schobben, H.P.M.; Smit, M.; Schobben, J.H.M.

1995-12-31

Risk analysis is mostly based on a comparison of one value for the exposure to a chemical (PEC) and one value for the sensitivity of biota (NEC). This method enables the determination of an effect to be expected, but it is not possible to quantify the magnitude of that effect. Moreover, it is impossible to estimate the effect of a combination of chemicals. Therefore, it is necessary to use a mathematical function to describe the relation between a concentration and the subsequent effect. These relations are typically based on a log normal or log logistic distribution of the sensitivity ofmore » individuals of a species. This distribution is characterized by the median sensitivity (EC{sub 50}) and the variation between the sensitivity of individuals (being a measure for the slope of the relation). Presently the attention is focused on the median, while the slope might be even more important. Relevant exposure concentrations are typically in the range which are found in the left tail of the sensitivity distribution. In this study the slope was determined for 250 chemical-species combinations. The data were derived from original experiments and from literature. The slope is highly dependent on the exposure time; the shorter the exposure time the steeper the slope. If data for a standard exposure time [96 hours] are considered, the total variation in slope can partly be explained by the groups of organisms and chemicals. The slope for heavy metals tends to be less steep as compared to the slope of narcotic organic compounds. The slope for fish and molluscs is steeper than for crustaceans. The results of this study are presently applied in a number of risk analysis studies.« less

Chemical management in fungicide sensivity of Mycosphaerella fijiensis collected from banana fields in México

PubMed Central

Aguilar-Barragan, Alejandra; García-Torres, Ana Elisa; Odriozola-Casas, Olga; Macedo-Raygoza, Gloria; Ogura, Tetsuya; Manzo-Sánchez, Gilberto; James, Andrew C.; Islas-Flores, Ignacio; Beltrán-García, Miguel J.

2014-01-01

The chemical management of the black leaf streak disease in banana caused by Mycosphaerella fijiensis (Morelet) requires numerous applications of fungicides per year. However this has led to fungicide resistance in the field. The present study evaluated the activities of six fungicides against the mycelial growth by determination of EC50 values of strains collected from fields with different fungicide management programs: Rustic management (RM) without applications and Intensive management (IM) more than 25 fungicide application/year. Results showed a decreased sensitivity to all fungicides in isolates collected from IM. Means of EC50 values in mg L−1 for RM and IM were: 13.25 ± 18.24 and 51.58 ± 46.14 for azoxystrobin, 81.40 ± 56.50 and 1.8575 ± 2.11 for carbendazim, 1.225 ± 0.945 and 10.01 ± 8.55 for propiconazole, 220 ± 67.66 vs. 368 ± 62.76 for vinclozolin, 9.862 ± 3.24 and 54.5 ± 21.08 for fludioxonil, 49.2125 ± 34.11 and 112.25 ± 51.20 for mancozeb. A molecular analysis for β-tubulin revealed a mutation at codon 198 in these strains having an EC50 greater than 10 mg L−1 for carbendazim. Our data indicate a consistency between fungicide resistance and intensive chemical management in banana fields, however indicative values for resistance were also found in strains collected from rustic fields, suggesting that proximity among fields may be causing a fungus interchange, where rustic fields are breeding grounds for development of resistant strains. Urgent actions are required in order to avoid fungicide resistance in Mexican populations of M. fijiensis due to fungicide management practices. PMID:24948956

In vitro antiretroviral activity and in vivo toxicity of the potential topical microbicide copper phthalocyanine sulfate.

PubMed

Styczynski, Ashley R; Anwar, Khandaker N; Sultana, Habiba; Ghanem, Abdelhamid; Lurain, Nell; Chua, Aishi; Ghassemi, Mahmood; Novak, Richard M

2015-08-30

Copper has antimicrobial properties and has been studied for its activity against viruses, including HIV. Copper complexed within a phthalocyanine ring, forming copper (II) phthalocyanine sulfate (CuPcS), may have a role in microbicide development when used intravaginally. CuPcS toxicity was tested against cervical epithelial cells, TZM-BL cells, peripheral blood mononuclear cells (PBMC), and cervical explant tissues using cell viability assays. In vivo toxicity was assessed following intravaginal administration of CuPcS in female BALB/C mice and measured using a standardized histology grading system on reproductive tract tissues. Efficacy studies for preventing infection with HIV in the presence of various non-toxic concentrations of CuPcS were carried out in TZM-BL, PBMC, and cervical explant cultures using HIV-1BAL and various pseudovirus subtypes. Non-linear regression was applied to the data to determine the EC50/90 and CC50/90. CuPcS demonstrated inhibition of HIV infection in PBMCs at concentrations that were non-toxic in cervical epithelial cells and PBMCs with EC50 values of approximately 50 μg/mL. Reproductive tract tissue analysis revealed no toxicity at 100 mg/mL. Human cervical explant tissues challenged with HIV in the presence of CuPcS also revealed a dose-response effect at preventing HIV infection at non-toxic concentrations with an EC50 value of 65 μg/mL. These results suggest that CuPcS may be useful as a topical microbicide in concentrations that can be achieved in the female genital tract.

Subchronic mercury exposure in coturnix and a method of hazard evaluation

USGS Publications Warehouse

Hill, E.F.; Soares, J.H.

1984-01-01

The sublethal toxicity of inorganic (HgCI 2) and organic (CH3HgCI) mercury chloride was studied in coturnix (Corurnix japonica) by feeding them mercuric compounds (CH3HgCI at concentrations of 0.125,0.5,2 and 8 ppm; HgCI2 at 0.5, 2, 8 and 32 ppm) in ad libitum diets from hatching to adulthood. Differences of response to the mercurials were compared on the basis of selected indicator enzymes and plasma chemistries. Comparisons of response to equivalent concentrations of the two mercurials and dose-response relationships were made at 1,3,5,7 and 9 weeks. Changes of activity were detected for brain acetylcholinesterase (AChE) and the plasma enzymes aspartate aminotransferase (ASA T), butyrylcholinesterase (BChE), lactate dehydrogenase (LDH) and ornithine carbamoyl transferase (OCT). Changes of ASA T, LDH and OCT were then quantified by probit analysis and the mercurials were compared through their median effective concentrations (EC50). This quantal procedure was based on the establishment of normal control values for each enzyme and then classifying mercury-treated outliers (more than + 2 SD) as respondents. The EC50 values at 9 weeks for ASA T, LDH and OCT, respectively, were 9, 3 and 63 ppm for HgCl 2, and 5, 1 and 4 ppm for CH3HgCI. These results provided the basis for two hazard indices that were calculated by dividing the EC50 into the oral LD50 and the 5-d dietary LC50. Mercury also had contradictory effects on gonadal maturation in both sexes.

Influence of soil properties and soil leaching on the toxicity of ionic silver to plants.

PubMed

Langdon, Kate A; McLaughlin, Mike J; Kirby, Jason K; Merrington, Graham

2015-11-01

Silver (Ag) has been shown to exhibit antimicrobial properties; as a result, it is being used increasingly in a wide range of consumer products. With these uses, the likelihood that Ag may enter the environment has increased, predominately via land application of biosolids or irrigation with treated wastewater effluent. The aim of the present study was to investigate the toxicity of Ag to 2 plant species: barley (Hordeum vulgare L. CV Triumph) and tomato (Lycopersicum esculentum) in a range of soils under both leached and unleached conditions. The concentrations that resulted in a 50% reduction of plant growth (EC50) were found to vary up to 20-fold across the soils, indicating a large influence of soil type on Ag toxicity. Overall, barley root elongation was found to be the least sensitive to added Ag, with EC50 values ranging from 51 mg/kg to 1030 mg/kg, whereas the tomato plant height showed higher sensitivity with EC50 values ranging from 46 mg/kg to 486 mg/kg. The effect of leaching was more evident in the barley toxicity results, where higher concentrations of Ag were required to induce toxicity. Variations in soil organic carbon and pH were found to be primarily responsible for mitigating Ag toxicity; therefore, these properties may be used in future risk assessments for Ag to predict toxicity in a wide range of soil types. © 2015 SETAC.

An interlaboratory comparison of nanosilver characterisation and hazard identification: Harmonising techniques for high quality data.

PubMed

Jemec, Anita; Kahru, Anne; Potthoff, Annegret; Drobne, Damjana; Heinlaan, Margit; Böhme, Steffi; Geppert, Mark; Novak, Sara; Schirmer, Kristin; Rekulapally, Rohit; Singh, Shashi; Aruoja, Villem; Sihtmäe, Mariliis; Juganson, Katre; Käkinen, Aleksandr; Kühnel, Dana

2016-02-01

Within the FP7 EU project NanoValid a consortium of six partners jointly investigated the hazard of silver nanoparticles (AgNPs) paying special attention to methodical aspects that are important for providing high-quality ecotoxicity data. Laboratories were supplied with the same original stock dispersion of AgNPs. All partners applied a harmonised procedure for storage and preparation of toxicity test suspensions. Altogether ten different toxicity assays with a range of environmentally relevant test species from different trophic levels were conducted in parallel to AgNP characterisation in the respective test media. The paper presents a comprehensive dataset of toxicity values and AgNP characteristics like hydrodynamic sizes of AgNP agglomerates and the share (%) of Ag(+)-species (the concentration of Ag(+)-species in relation to the total measured concentration of Ag). The studied AgNP preparation (20.4±6.8 nm primary size, mean total Ag concentration 41.14 mg/L, 46-68% of soluble Ag(+)-species in stock, 123.8±12.2 nm mean z-average value in dH2O) showed extreme toxicity to crustaceans Daphnia magna, algae Pseudokirchneriella subcapitata and zebrafish Danio rerio embryos (EC50<0.01 mg total Ag/L), was very toxic in the in vitro assay with rainbow trout Oncorhynchus mykiss gut cells (EC50: 0.01-1 mg total Ag/L); toxic to bacteria Vibrio fischeri, protozoa Tetrahymena thermophila (EC50: 1-10 mg total Ag/L) and harmful to marine crustaceans Artemia franciscana (EC50: 10-100 mg total Ag/L). Along with AgNPs, also the toxicity of AgNO3 was analyzed. The toxicity data revealed the same hazard ranking for AgNPs and AgNO3 (i.e. the EC50 values were in the same order of magnitude) proving the importance of soluble Ag(+)-species analysis for predicting the hazard of AgNPs. The study clearly points to the need for harmonised procedures for the characterisation of NMs. Harmonised procedures should consider: (i) measuring the AgNP properties like hydrodynamic size and metal ions species in each toxicity test medium at a range of concentrations, and (ii) including soluble metal salt control both in toxicity testing as well as in Ag(+)-species measurements. The present study is among the first nanomaterial interlaboratory comparison studies with the aim to improve the hazard identification testing protocols. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Inoculum Effect on the Efficacies of Amoxicillin-Clavulanate, Piperacillin-Tazobactam, and Imipenem against Extended-Spectrum β-Lactamase (ESBL)-Producing and Non-ESBL-Producing Escherichia coli in an Experimental Murine Sepsis Model

PubMed Central

López-Cerero, L.; López-Rojas, R.; Egea, P.; Domínguez-Herrera, J.; Rodríguez-Baño, J.; Pascual, A.; Pachón, J.

2013-01-01

Escherichia coli is commonly involved in infections with a heavy bacterial burden. Piperacillin-tazobactam and carbapenems are among the recommended empirical treatments for health care-associated complicated intra-abdominal infections. In contrast to amoxicillin-clavulanate, both have reduced in vitro activity in the presence of high concentrations of extended-spectrum β-lactamase (ESBL)-producing and non-ESBL-producing E. coli bacteria. Our goal was to compare the efficacy of these antimicrobials against different concentrations of two clinical E. coli strains, one an ESBL-producer and the other a non-ESBL-producer, in a murine sepsis model. An experimental sepsis model {∼5.5 log10 CFU/g [low inoculum concentration (LI)] or ∼7.5 log10 CFU/g [high inoculum concentration (HI)]} using E. coli strains ATCC 25922 (non-ESBL producer) and Ec1062 (CTX-M-14 producer), which are susceptible to the three antimicrobials, was used. Amoxicillin-clavulanate (50/12.5 mg/kg given intramuscularly [i.m.]), piperacillin-tazobactam (25/3.125 mg/kg given intraperitoneally [i.p.]), and imipenem (30 mg/kg i.m.) were used. Piperacillin-tazobactam and imipenem reduced spleen ATCC 25922 strain concentrations (−2.53 and −2.14 log10 CFU/g [P < 0.05, respectively]) in the HI versus LI groups, while amoxicillin-clavulanate maintained its efficacy (−1.01 log10 CFU/g [no statistically significant difference]). Regarding the Ec1062 strain, the antimicrobials showed lower efficacy in the HI than in the LI groups: −0.73, −1.89, and −1.62 log10 CFU/g (P < 0.05, for piperacillin-tazobactam, imipenem, and amoxicillin-clavulanate, respectively, although imipenem and amoxicillin-clavulanate were more efficacious than piperacillin-tazobactam). An adapted imipenem treatment (based on the time for which the serum drug concentration remained above the MIC obtained with a HI of the ATCC 25922 strain) improved its efficacy to −1.67 log10 CFU/g (P < 0.05). These results suggest that amoxicillin-clavulanate could be an alternative to imipenem treatment of infections caused by ESBL- and non-ESBL-producing E. coli strains in patients with therapeutic failure with piperacillin-tazobactam. PMID:23439636

Inoculum effect on the efficacies of amoxicillin-clavulanate, piperacillin-tazobactam, and imipenem against extended-spectrum β-lactamase (ESBL)-producing and non-ESBL-producing Escherichia coli in an experimental murine sepsis model.

PubMed

Docobo-Pérez, F; López-Cerero, L; López-Rojas, R; Egea, P; Domínguez-Herrera, J; Rodríguez-Baño, J; Pascual, A; Pachón, J

2013-05-01

Escherichia coli is commonly involved in infections with a heavy bacterial burden. Piperacillin-tazobactam and carbapenems are among the recommended empirical treatments for health care-associated complicated intra-abdominal infections. In contrast to amoxicillin-clavulanate, both have reduced in vitro activity in the presence of high concentrations of extended-spectrum β-lactamase (ESBL)-producing and non-ESBL-producing E. coli bacteria. Our goal was to compare the efficacy of these antimicrobials against different concentrations of two clinical E. coli strains, one an ESBL-producer and the other a non-ESBL-producer, in a murine sepsis model. An experimental sepsis model {~5.5 log10 CFU/g [low inoculum concentration (LI)] or ~7.5 log(10) CFU/g [high inoculum concentration (HI)]} using E. coli strains ATCC 25922 (non-ESBL producer) and Ec1062 (CTX-M-14 producer), which are susceptible to the three antimicrobials, was used. Amoxicillin-clavulanate (50/12.5 mg/kg given intramuscularly [i.m.]), piperacillin-tazobactam (25/3.125 mg/kg given intraperitoneally [i.p.]), and imipenem (30 mg/kg i.m.) were used. Piperacillin-tazobactam and imipenem reduced spleen ATCC 25922 strain concentrations (-2.53 and -2.14 log10 CFU/g [P < 0.05, respectively]) in the HI versus LI groups, while amoxicillin-clavulanate maintained its efficacy (-1.01 log10 CFU/g [no statistically significant difference]). Regarding the Ec1062 strain, the antimicrobials showed lower efficacy in the HI than in the LI groups: -0.73, -1.89, and -1.62 log10 CFU/g (P < 0.05, for piperacillin-tazobactam, imipenem, and amoxicillin-clavulanate, respectively, although imipenem and amoxicillin-clavulanate were more efficacious than piperacillin-tazobactam). An adapted imipenem treatment (based on the time for which the serum drug concentration remained above the MIC obtained with a HI of the ATCC 25922 strain) improved its efficacy to -1.67 log10 CFU/g (P < 0.05). These results suggest that amoxicillin-clavulanate could be an alternative to imipenem treatment of infections caused by ESBL- and non-ESBL-producing E. coli strains in patients with therapeutic failure with piperacillin-tazobactam.

Cell Density Affects the Detection of Chk1 Target Engagement by the Selective Inhibitor V158411.

PubMed

Geneste, Clara C; Massey, Andrew J

2018-02-01

Understanding drug target engagement and the relationship to downstream pharmacology is critical for drug discovery. Here we have evaluated target engagement of Chk1 by the small-molecule inhibitor V158411 using two different target engagement methods (autophosphorylation and cellular thermal shift assay [CETSA]). Target engagement measured by these methods was subsequently related to Chk1 inhibitor-dependent pharmacology. Inhibition of autophosphorylation was a robust method for measuring V158411 Chk1 target engagement. In comparison, while target engagement determined using CETSA appeared robust, the V158411 CETSA target engagement EC 50 values were 43- and 19-fold greater than the autophosphorylation IC 50 values. This difference was attributed to the higher cell density in the CETSA assay configuration. pChk1 (S296) IC 50 values determined using the CETSA assay conditions were 54- and 33-fold greater than those determined under standard conditions and were equivalent to the CETSA EC 50 values. Cellular conditions, especially cell density, influenced the target engagement of V158411 for Chk1. The effects of high cell density on apparent compound target engagement potency should be evaluated when using target engagement assays that necessitate high cell densities (such as the CETSA conditions used in this study). In such cases, the subsequent relation of these data to downstream pharmacological changes should therefore be interpreted with care.

Accurate prediction of acute fish toxicity of fragrance chemicals with the RTgill-W1 cell assay.

PubMed

Natsch, Andreas; Laue, Heike; Haupt, Tina; von Niederhäusern, Valentin; Sanders, Gordon

2018-03-01

Testing for acute fish toxicity is an integral part of the environmental safety assessment of chemicals. A true replacement of primary fish tissue was recently proposed using cell viability in a fish gill cell line (RTgill-W1) as a means of predicting acute toxicity, showing good predictivity on 35 chemicals. To promote regulatory acceptance, the predictivity and applicability domain of novel tests need to be carefully evaluated on chemicals with existing high-quality in vivo data. We applied the RTgill-W1 cell assay to 38 fragrance chemicals with a wide range of both physicochemical properties and median lethal concentration (LC50) values and representing a diverse range of chemistries. A strong correlation (R 2  = 0.90-0.94) between the logarithmic in vivo LC50 values, based on fish mortality, and the logarithmic in vitro median effect concentration (EC50) values based on cell viability was observed. A leave-one-out analysis illustrates a median under-/overprediction from in vitro EC50 values to in vivo LC50 values by a factor of 1.5. This assay offers a simple, accurate, and reliable alternative to in vivo acute fish toxicity testing for chemicals, presumably acting mainly by a narcotic mode of action. Furthermore, the present study provides validation of the predictivity of the RTgill-W1 assay on a completely independent set of chemicals that had not been previously tested and indicates that fragrance chemicals are clearly within the applicability domain. Environ Toxicol Chem 2018;37:931-941. © 2017 SETAC. © 2017 SETAC.

Combinatorial Pharmacodynamics of Ceftolozane-Tazobactam against Genotypically Defined β-Lactamase-Producing Escherichia coli: Insights into the Pharmacokinetics/Pharmacodynamics of β-Lactam–β-Lactamase Inhibitor Combinations

PubMed Central

Soon, Rachel L.; Lenhard, Justin R.; Bulman, Zackery P.; Holden, Patricia N.; Kelchlin, Pamela; Steenbergen, Judith N.; Friedrich, Lawrence V.; Forrest, Alan

2016-01-01

Despite a dearth of new agents currently being developed to combat multidrug-resistant Gram-negative pathogens, the combination of ceftolozane and tazobactam was recently approved by the Food and Drug Administration to treat complicated intra-abdominal and urinary tract infections. To characterize the activity of the combination product, time-kill studies were conducted against 4 strains of Escherichia coli that differed in the type of β-lactamase they expressed. The four investigational strains included 2805 (no β-lactamase), 2890 (AmpC β-lactamase), 2842 (CMY-10 β-lactamase), and 2807 (CTX-M-15 β-lactamase), with MICs to ceftolozane of 0.25, 4, 8, and >128 mg/liter with no tazobactam, and MICs of 0.25, 1, 4, and 8 mg/liter with 4 mg/liter tazobactam, respectively. All four strains were exposed to a 6 by 5 array of ceftolozane (0, 1, 4, 16, 64, and 256 mg/liter) and tazobactam (0, 1, 4, 16, and 64 mg/liter) over 48 h using starting inocula of 106 and 108 CFU/ml. While ceftolozane-tazobactam achieved bactericidal activity against all 4 strains, the concentrations of ceftolozane and tazobactam required for a ≥3-log reduction varied between the two starting inocula and the 4 strains. At both inocula, the Hill plots (R2 > 0.882) of ceftolozane revealed significantly higher 50% effective concentrations (EC50s) at tazobactam concentrations of ≤4 mg/liter than those at concentrations of ≥16 mg/liter (P < 0.01). Moreover, the EC50s at 108 CFU/ml were 2.81 to 66.5 times greater than the EC50s at 106 CFU/ml (median, 10.7-fold increase; P = 0.002). These promising results indicate that ceftolozane-tazobactam achieves bactericidal activity against a wide range of β-lactamase-producing E. coli strains. PMID:26729494

Biochemical and toxicological effects of organic (herbicide Primextra(®) Gold TZ) and inorganic (copper) compounds on zooplankton and phytoplankton species.

PubMed

Filimonova, Valentina; Gonçalves, Fernando; Marques, João C; De Troch, Marleen; Gonçalves, Ana M M

2016-08-01

In Europe, mainly in the Mediterranean region, an intensive usage of pesticides was recorded during the past 30 years. According to information from agricultural cooperatives of the Mondego valley (Figueira da Foz, Portugal), Primextra(®) Gold TZ is the most used herbicide in corn crop fields and one of the 20 best-selling herbicides in Portugal. Copper is mainly used in pesticide formulations. This study aims to determine the ecotoxicological and biochemical (namely fatty acid profiles) effects of the herbicide Primextra(®) Gold TZ and the metal copper on marine plankton. The organisms used in this study are three planktonic species: the marine diatom Thalassiosira weissflogii, the estuarine copepod Acartia tonsa and nauplii of the marine brine shrimp Artemia franciscana. Fatty acids (FAs) are one of the most important molecules transferred across the plant-animal interface in aquatic food webs and can be used as good indicators of stress. The conducted lab incubations show that T. weissflogii is the most sensitive species to the herbicide followed by A. tonsa (EC50=0.0078mg/L and EC50=0.925mg/L, respectively), whereas the copepod was the most sensitive species to the metal followed by T. weissflogii (EC50=0.234mg/L and EC50=0.383mg/L, respectively). A. franciscana was the most tolerant organism both to the herbicide and to the metal (EC50=20.35mg/L and EC50=18.93mg/L, respectively). Changes in the FA profiles of primary producer and primary consumers were observed, with the increase of saturated FA and decrease of unsaturated FA contents, especially of highly unsaturated FAs that can be obtained mainly from food and therefore are referred to as 'essential FA'. The study suggests that discharges of Primextra(®) Gold TZ or other pesticides mainly composed by copper may be a threat to plankton populations causing changes in the FA contents and thus in their nutritive value, with severe repercussions for higher trophic levels and thus the entire food web. Copyright © 2016 Elsevier B.V. All rights reserved.

Quantitative structure toxicity relationships for phenols in isolated rat hepatocytes.

PubMed

Moridani, Majid Y; Siraki, Arno; O'Brien, Peter J

2003-05-06

Quantitative structure toxicity relationship (QSTR) equations were obtained to predict and describe the cytotoxicity of 31 phenols using logLD(50) as a concentration to induce 50% cytotoxicity of isolated rat hepatocytes in 2 h and logP as octanol/water partitioning: logLD(50) (microM)=-0.588(+/-0.059)logP+4.652(+/-0.153) (n=27, r(2)=0.801, s=0.261, P<1 x 10(-9)). Hydroquinone, catechol, 4-nitrophenol, and 2,4-dinitrophenol were outliers for this equation. When the ionization constant pK(a) was considered as a contributing factor a two-parameter QSTR equation was derived: logLD(50) (microM)=-0.595(+/-0.051)logP+0.197(+/-0.029)pK(a)+2.665(+/-0.281) (n=28, r(2)=0.859, s=0.218, P<1 x 10(-6)). Using sigma+, the Brown variation of the Hammet electronic constant, as a contributing parameter, the cytotoxicity of phenols towards hepatocytes were defined by logLD(50) (microM)=-0.594(+/-0.052)logP-0.552(+/-0.085)sigma+ +4.540(+/-0.132) (n=28, r(2)=0.853, s=0.223, P<1 x 10(-6)). Replacing sigma+ with the homolytic bond dissociation energy (BDE) for (X-PhOH+PhO.-->X-PhO.+PhOH) led to logLD(50) (microM)=-0.601(+/-0.066)logP-0.040(+/-0.018)BDE+4.611(+/-0.166) (n=23, r(2)=0.827, s=0.223, P<0.05). Hydroquinone, catechol and 2-nitrophenol were outliers for the above equations. Using redox potential and logP led to a new correlation: logLD(50) (microM)=-0.529(+/-0.135)logP+2.077(+/-0.892)E(p/2)+2.806(+/-0.592) (n=15, r(2)=0.561, s=0.383, P<0.05) with 4-nitrophenol as an outlier. Our findings indicate that phenols with higher lipophilicity, BDE, or sigma+ values or with lower pK(a) and redox potential were more toxic towards hepatocytes. We also showed that a collapse of hepatocyte mitochondrial membrane potential preceded the cytotoxicity of most phenols. Our study indicates that one or a combination of mechanisms; i.e. mitochondrial uncoupling, phenoxy radicals, or phenol metabolism to quinone methides and quinones, contribute to phenol cytotoxicity towards hepatocytes depending on the phenol chemical structure.

Lead toxicity thresholds in 17 Chinese soils based on substrate-induced nitrification assay.

PubMed

Li, Ji; Huang, Yizong; Hu, Ying; Jin, Shulan; Bao, Qiongli; Wang, Fei; Xiang, Meng; Xie, Huiting

2016-06-01

The influence of soil properties on toxicity threshold values for Pb toward soil microbial processes is poorly recognized. The impact of leaching on the Pb threshold has not been assessed systematically. Lead toxicity was screened in 17 Chinese soils using a substrate-induced nitrification (SIN) assay under both leached and unleached conditions. The effective concentration of added Pb causing 50% inhibition (EC50) ranged from 185 to >2515mg/kg soil for leached soil and 130 to >2490mg/kg soil for unleached soil. These results represented >13- and >19-fold variations among leached and unleached soils, respectively. Leaching significantly reduced Pb toxicity for 70% of both alkaline and acidic soils tested, with an average leaching factor of 3.0. Soil pH and CEC were the two most useful predictors of Pb toxicity in soils, explaining over 90% of variance in the unleached EC50 value. The relationships established in the present study predicted Pb toxicity within a factor of two of measured values. These relationships between Pb toxicity and soil properties could be used to establish site-specific guidance on Pb toxicity thresholds. Copyright © 2016. Published by Elsevier B.V.

Hygienic Status Assessment of Two Lamb Slaughterhouses in Spain.

PubMed

Alonso-Calleja, Carlos; Guerrero-Ramos, Emilia; Capita, Rosa

2017-07-01

A total of 180 lamb carcasses and 200 inert surfaces were sampled in two commercial abattoirs (plants A and B) from northwest Spain. A higher (P < 0.001) average microbial load (log CFU per square centimeter) on lamb carcasses was observed for total viable counts (TVC; 2.74 ± 1.15) than for Enterobacteriaceae (2.21 ± 1.16). Different microbial counts were found on carcasses from plants A and B, both for TVC (2.56 ± 0.96 versus 3.18 ± 1.47, respectively; P < 0.001) and Enterobacteriaceae (2.09 ± 0.97 versus 2.50 ± 1.61, respectively; P < 0.05). High correlations (P < 0.001) were observed for TVC and Enterobacteriaceae in both plants A (r = 0.708) and B (r = 0.912). The percentages of unsatisfactory daily mean log values for carcasses, according to European Union Regulation (EC) No 2073/2005, were 0.0 (TVC) and 30.8 (Enterobacteriaceae) in plant A and 10.0 (TVC) and 40.0 (Enterobacteriaceae) in plant B. Average counts for inert surfaces were all lower than 10 CFU/cm 2 (TVC) or 1 CFU/cm 2 (Enterobacteriaceae). The need to improve hygienic practices in order to adhere to the European Union microbiological performance criteria is emphasized. The detected different microbial counts between slaughterhouses could be attributed to differences in external hygiene of livestock and in the number of slaughterhouse workers. Microbiological analysis of carcasses and surfaces allows detection of hygienic concerns in the overall process.

In vitro anthelmintic activity of active compounds of the fringed rue Ruta chalepensis against dairy ewe gastrointestinal nematodes.

PubMed

Ortu, E; Sanna, G; Scala, A; Pulina, G; Caboni, P; Battacone, G

2017-07-01

Infections by gastrointestinal nematodes negatively affect small ruminant health and at the same time cause substantial economic losses worldwide. Because resistance to conventional anthelmintic compounds is growing, target studies evaluating the effectiveness of alternative ingredients of botanical origin on gastrointestinal nematodes are needed. In this study, we evaluated the in vitro anthelmintic activity of Ruta chalepensis L. extracts on the third-stage larvae of sheep gastrointestinal nematodes. A methanol extract showed the highest anthelmintic activity, with an EC50 = 0.10 ± 0.06 mg/ml after 96 h, while the essential oil had an EC50 = 1.45 ± 1.22 mg/ml after 48 h. Moreover, three secondary metabolites of the essential oil, i.e. 2-decanone, 2-nonanone and 2-undecanone, showed EC50 values of 0.07 ± 0.06, 0.25 ± 0.29 and 0.88 ± 0.73 mg/ml at 24 h, respectively. The present study indicated that the R. chalepensis methanol extract, the essential oil and its metabolites 2-decanone, 2-nonanone and 2-undecanone showed promising anthelmintic activity on gastrointestinal nematodes.

Development and validation of an OECD reproductive toxicity test guideline with the pond snail Lymnaea stagnalis (Mollusca, Gastropoda).

PubMed

Ducrot, Virginie; Askem, Clare; Azam, Didier; Brettschneider, Denise; Brown, Rebecca; Charles, Sandrine; Coke, Maïra; Collinet, Marc; Delignette-Muller, Marie-Laure; Forfait-Dubuc, Carole; Holbech, Henrik; Hutchinson, Thomas; Jach, Arne; Kinnberg, Karin L; Lacoste, Cédric; Le Page, Gareth; Matthiessen, Peter; Oehlmann, Jörg; Rice, Lynsey; Roberts, Edward; Ruppert, Katharina; Davis, Jessica Elphinstone; Veauvy, Clemence; Weltje, Lennart; Wortham, Ruth; Lagadic, Laurent

2014-12-01

The OECD test guideline development program has been extended in 2011 to establish a partial life-cycle protocol for assessing the reproductive toxicity of chemicals to several mollusk species, including the great pond snail Lymnaea stagnalis. In this paper, we summarize the standard draft protocol for a reproduction test with this species, and present inter-comparison results obtained in a 56-day prevalidation ring-test using this protocol. Seven European laboratories performed semi-static tests with cultured snails of the strain Renilys® exposed to nominal concentrations of cadmium chloride (from 53 to 608μgCdL(-1)). Cd concentrations in test solutions were analytically determined to confirm accuracy in the metal exposure concentrations in all laboratories. Physico-chemical and biological validity criteria (namely dissolved oxygen content >60% ASV, water temperature 20±1°C, control snail survival >80% and control snail fecundity >8 egg-masses per snail over the test period) were met in all laboratories which consistently demonstrated the reproductive toxicity of Cd in snails using the proposed draft protocol. Effect concentrations for fecundity after 56days were reproducible between laboratories (68

1,2-Dithiole-3-Ones as Potent Inhibitors of the Bacterial 3-Ketoacyl Acyl Carrier Protein Synthase III (FabH)

PubMed Central

He, Xin; Reeve, Anne McElwee; Desai, Umesh R.; Kellogg, Glen E.; Reynolds, Kevin A.

2004-01-01

The enzyme FabH catalyzes the initial step of fatty acid biosynthesis via a type II dissociated fatty acid synthase. The pivotal role of this essential enzyme, combined with its unique structural features and ubiquitous occurrence in bacteria, has made it an attractive new target for the development of antibacterial and antiparasitic compounds. We have searched the National Cancer Institute database for compounds bearing structural similarities to thiolactomycin, a natural product which exhibits a weak activity against FabH. This search has yielded several substituted 1,2-dithiole-3-ones that are potent inhibitors of FabH from both Escherichia coli (ecFabH) and Staphylococcus aureus (saFabH). The most potent inhibitor was 4,5-dichloro-1,2-dithiole-3-one, which had 50% inhibitory concentration (IC50) values of 2 μM (ecFabH) and 0.16 μM (saFabH). The corresponding 3-thione analog exhibited comparable activities. Analogs in which the 4-chloro substituent was replaced with a phenyl group were also potent inhibitors, albeit somewhat less effectively (IC50 values of 5.7 and 0.98 μM for ecFabH and saFabH, respectively). All of the 5-chlorinated inhibitors were most effective when they were preincubated with FabH in the absence of substrates. The resulting enzyme-inhibitor complex did not readily regain activity after excess inhibitor was removed, suggesting that a slow dissociation occurs. In stark contrast, a series of inhibitors in which the 5-chloro substituent was replaced with the isosteric and isoelectronic trifluoromethyl group were poorer inhibitors (IC50 values typically ranging from 25 to >100 μM for both ecFabH and saFabH), did not require a preincubation period for maximal activity, and generated an enzyme-inhibitor complex which readily dissociated. Possible modes of binding of 5-chloro-1,2-dithiole-3-ones and 5-chloro-1,2-dithiole-3-thiones with FabH which account for the role of the 5-chloro substituent were considered. PMID:15273125

Cytotoxicity and antiviral activities of Asplenium nidus, Phaleria macrocarpa and Eleusine indica

NASA Astrophysics Data System (ADS)

Tahir, Mariya Mohd; Ibrahim, Nazlina; Yaacob, Wan Ahmad

2014-09-01

Three local medicinal plants namely Asplenium nidus (langsuyar), Eleusine indica (sambau) and Phaleria macrocarpa (mahkota dewa) were screened for the cytotoxicity and antiviral activities. Six plant extracts were prepared including the aqueous and methanol extracts from A. nidus leaf and root, aqueous extract from dried whole plant of E. indica and methanol extract from P. macrocarpa fruits. Cytotoxicity screening in Vero cell line by MTT assay showed that the CC50 values ranged from 15 to 60 mg/mL thus indicating the safety of the extracts even at high concentrations. Antiviral properties of the plant extracts were determined by plaque reduction assay. The EC50 concentrations were between 3.2 to 47 mg/mL. The selectivity indices (SI = CC50/EC50) of each tested extracts ranged from 4.3 to 63.25 indicating the usefulness of the extracts as potential antiviral agents.

Applying mixture toxicity modelling to predict bacterial bioluminescence inhibition by non-specifically acting pharmaceuticals and specifically acting antibiotics.

PubMed

Neale, Peta A; Leusch, Frederic D L; Escher, Beate I

2017-04-01

Pharmaceuticals and antibiotics co-occur in the aquatic environment but mixture studies to date have mainly focused on pharmaceuticals alone or antibiotics alone, although differences in mode of action may lead to different effects in mixtures. In this study we used the Bacterial Luminescence Toxicity Screen (BLT-Screen) after acute (0.5 h) and chronic (16 h) exposure to evaluate how non-specifically acting pharmaceuticals and specifically acting antibiotics act together in mixtures. Three models were applied to predict mixture toxicity including concentration addition, independent action and the two-step prediction (TSP) model, which groups similarly acting chemicals together using concentration addition, followed by independent action to combine the two groups. All non-antibiotic pharmaceuticals had similar EC 50 values at both 0.5 and 16 h, indicating together with a QSAR (Quantitative Structure-Activity Relationship) analysis that they act as baseline toxicants. In contrast, the antibiotics' EC 50 values decreased by up to three orders of magnitude after 16 h, which can be explained by their specific effect on bacteria. Equipotent mixtures of non-antibiotic pharmaceuticals only, antibiotics only and both non-antibiotic pharmaceuticals and antibiotics were prepared based on the single chemical results. The mixture toxicity models were all in close agreement with the experimental results, with predicted EC 50 values within a factor of two of the experimental results. This suggests that concentration addition can be applied to bacterial assays to model the mixture effects of environmental samples containing both specifically and non-specifically acting chemicals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of some commonly used pesticides on seed germination, biomass production and photosynthetic pigments in tomato (Lycopersicon esculentum).

PubMed

Shakir, Shakirullah Khan; Kanwal, Memoona; Murad, Waheed; Zia ur Rehman; Shafiq ur Rehman; Daud, M K; Azizullah, Azizullah

2016-03-01

Pesticides are highly toxic substances. Their toxicity may not be absolutely specific to the target organisms but can adversely affect different processes in the non-target host plants. In the present study, the effect of over application of four commonly used pesticides (emamectin benzoate, alpha-cypermethrin, lambda-cyhalothrin and imidacloprid) was evaluated on the germination, seedling vigor and photosynthetic pigments in tomato. The obtained results revealed that seed germination was decreased by the pesticides and this effect was more prominent at early stages of exposure. All the tested pesticides reduced the growth of tomato when applied in higher concentration than the recommended dose, but at lower doses the pesticides had some stimulatory effects on growth as compared to the control. A similar effect of pesticides was observed on the photosynthetic pigments, i.e. a decrease in pigments concentrations was caused at higher doses but an increase was observed at lower doses of pesticides. The calculation of EC50 values for different parameters revealed the lowest EC50 values for emamectin (ranged as 51-181 mg/L) followed by alpha-cypermethrin (191.74-374.39), lambda-cyhalothrin (102.43-354.28) and imidacloprid (430.29-1979.66 mg/L). A comparison of the obtained EC50 values for different parameters of tomato with the recommended doses revealed that over application of these pesticides can be harmful to tomato crop. In a few cases these pesticides were found toxic even at the recommended doses. However, a field based study in this regard should be conducted to further verify these results.

Acute aquatic toxicity of tire and road wear particles to alga, daphnid, and fish.

PubMed

Marwood, Christopher; McAtee, Britt; Kreider, Marisa; Ogle, R Scott; Finley, Brent; Sweet, Len; Panko, Julie

2011-11-01

Previous studies have indicated that tire tread particles are toxic to aquatic species, but few studies have evaluated the toxicity of such particles using sediment, the likely reservoir of tire wear particles in the environment. In this study, the acute toxicity of tire and road wear particles (TRWP) was assessed in Pseudokirchneriella subcapita, Daphnia magna, and Pimephales promelas using a sediment elutriate (100, 500, 1000 or 10000 mg/l TRWP). Under standard test temperature conditions, no concentration response was observed and EC/LC(50) values were greater than 10,000 mg/l. Additional tests using D. magna were performed both with and without sediment in elutriates collected under heated conditions designed to promote the release of chemicals from the rubber matrix to understand what environmental factors may influence the toxicity of TRWP. Toxicity was only observed for elutriates generated from TRWP leached under high-temperature conditions and the lowest EC/LC(50) value was 5,000 mg/l. In an effort to identify potential toxic chemical constituent(s) in the heated leachates, toxicity identification evaluation (TIE) studies and chemical analysis of the leachate were conducted. The TIE coupled with chemical analysis (liquid chromatography/mass spectrometry/mass spectrometry [LC/MS/MS] and inductively coupled plasma/mass spectrometry [ICP/MS]) of the leachate identified zinc and aniline as candidate toxicants. However, based on the high EC/LC(50) values and the limited conditions under which toxicity was observed, TRWP should be considered a low risk to aquatic ecosystems under acute exposure scenarios.

Airways and vascular smooth muscles relaxant activities of Gaultheria trichophylla.

PubMed

Alam, Fiaz; Saqib, Qazi Najumus; Shah, Abdul Jabbar

2017-01-01

The aim of this experimental work was to explore the potential pharmacological activities of Gaultheria trichophylla Royle in hyperactive respiratory and vascular conditions. Gaultheria trichophylla was extracted with solvents, phytochemical detection tests were performed, and rabbit trachea and aorta strips were used to evaluate its effects on airways and vascular smooth muscles. Qualitative phytochemical tests showed the presence of flavonoids, alkaloids, anthraquinones, saponins, terpenoids, and condensed tannins. The methanol extract caused inhibition (EC 50 values of 3.12 mg/mL) of carbachol (1 μM) and partial relaxation of K + (80 mM) caused contractions in tracheal strips. The chloroform extract was comparatively more potent against carbachol than K+ induced contraction with EC 50 values of 0.64 and 2.26 mg/mL, respectively. However, the n-hexane extract showed more potency against K + than cabachol induced contractions, as in case with verapamil, with EC 50 values of 0.61 and 6.58 mg/mL, respectively. In isolated prepared trachea, the extracts displaced the carbachol concentration response curves and maximum response was suppressed. In rabbit aorta preparations, methanol and n-hexane extracts partially relaxed phenylephrine (1 μM) and K + induced vasoconstrictions. However, the chloroform extract inhibited phenylephrine induced contractions and exhibited a vasoconstrictor effect at lower concentrations and a relaxant effect at higher concentrations against K + precontractions. The data indicates that, in addition to others, the extracts of G .trichophylla possess verapamil like Ca ++ channel blocking components which explain the possible role of this plant in respiratory and vascular conditions.

Effects of chain length, chlorination degree, and structure on the octanol-water partition coefficients of polychlorinated n-alkanes.

PubMed

Hilger, Bettina; Fromme, Hermann; Völkel, Wolfgang; Coelhan, Mehmet

2011-04-01

Log octanol-water partition coefficients (log Kow) of 40 synthesized polychlorinated n-alkanes (PCAs) with different chlorination degrees were determined using reversed-phase high performance liquid chromatography (RP-HPLC). In addition, log Kow values of a technical mixture namely Cereclor 63L as well as 15 individual in house synthesized C10, C11, and C12 chloroalkanes with known chlorine positions were estimated. Based on these results, the effects of chain length, chlorination degree, and structure were explored. The estimated log Kow values ranged from 4.10 (polychlorinated n-decanes with 50.2% chlorine content) to 11.34 (polychlorinated n-octacosanes with 54.8% chlorine content) for PCAs and from 3.82 (1,2,5,6,9,10-hexachlorodecane) to 7.75 (1,1,1,3,9,11,11,11-octachlorododecane) for the individual chloroalkanes studied. The results showed that log Kow value was influenced linearly at a given chlorine content by chain length, while a polynominal effect was observed in dependence on the chlorination degree of an alkane chain. Chlorine substitution pattern influenced markedly the log Kow value of chloroalkanes.

Bi-spectral index, entropy and predicted plasma propofol concentrations with target controlled infusions in Indian patients.

PubMed

Puri, Goverdhan D; Mathew, Preethy J; Sethu Madhavan, J; Hegde, Harihar V; Fiehn, Andreas

2011-10-01

Many processed electroencephalographic signals are used now to help the anaesthesiologist titrate the depth of sedation. We investigated the relationship between target plasma propofol concentration and objective end-points of sedation- Bispectral Index (BIS), State Entropy (SE) and Response Entropy (RE)-at clinical end-points as assessed by Modified Observer Assessment of Alertness/sedation Scale (MOAAS) in Indian patients. Eighteen ASA 1 and 2 Indian adult patients scheduled to undergo elective surgery were included. The target control infusion (TCI) of propofol was administered using 'Diprifusor'. The level of sedation was assessed using MOAAS by the anaesthesiologist. BIS, SE, RE were recorded throughout. TCI was started at 0.5 μg/ml and increased by 0.5 μg/ml every 6 min till MOAAS scores reached 0 or there was sustained BIS value less than 30. The EC(50) and EC(95) of predicted plasma propofol concentration for loss of consciousness (assessed by loss of response to verbal command), were 2.3 and 2.8 μg/ml respectively and for loss of response to painful stimuli (trapezius squeeze) were 4.0 and 5.0 μg/ml respectively. The BIS and entropy values (EC(50) and EC(95)) for loss of consciousness and response to painful stimuli in Indian patients were estimated. The preliminary relation of target plasma propofol concentration with BIS was found to be BIS = 100.5-16.4 × (Target concentration). The target plasma propofol concentrations required to produce unconsciousness and loss of response to painful stimuli in Indian patients have been estimated. Also, the relations between target plasma concentration and objective measures of different levels of anaesthesia have been established.

Advantage of using CBA/N strain mice in a non-radioisotopic modification of the local lymph node assay.

PubMed

Takeyoshi, Masahiro; Noda, Shuji; Yamasaki, Kanji; Kimber, Ian

2006-01-01

The murine local lymph node assay (LLNA) is currently recognized as a stand-alone test method for determining the skin sensitizing potential of chemicals. It has been incorporated into the official test guidelines published by some authorities, including the OECD. To avoid the use of radioisotopes, efforts have been made recently to develop non-radioisotopic modifications of the LLNA. A non-radioisotopic modification of the LLNA was developed previously using 5-bromo-2'-deoxyuridine (BrdU) incorporation (non-RI LLNA). However, the non-RI LLNA was found to be somewhat less sensitive than the standard assay. This study reports the advantage of using mice of the CBA/N strain in the non-RI LLNA to improve the sensitivity of this method. The non-RI LLNA was performed using CBA/JN and CBA/N mice exposed to one of four confirmed skin sensitizers, 2,4-dinitrochlorobenzene (DNCB), eugenol (EG), isoeugenol (IEG) or alpha-hexylcinnamic aldehyde (HCA), and to one non-sensitizer, propylene glycol (PG). The EC3 values for DNCB, IEG, EG, HCA and PG were calculated to be 0.1%, 9.6%, 40.6%, 45.5% and >50% in CBA/JN mice and 0.08%, 1.9%, 10.7%, 20.3% and >50% in CBA/N mice, respectively. The EC3 values for DNCB, IEG, EG, HCA and PG in the standard LLNA using CBA/Ca mice and radioisotopes were reported elsewhere as being 0.08%, 1.3%, 13.0%, 8.0% and >50%, respectively. The EC3 values derived from the CBA/N mice in the non-RI LLNA were nearly equivalent to the EC3 values obtained using the standard radioisotopic LLNA with CBA/Ca mice. These data suggest that the use of CBA/N mice may provide a realistic opportunity to develop a version of the LLNA that does not have a requirement for the use of radioisotopes, but which nevertheless has sensitivity approaching, or comparable to, the standard method. 2005 John Wiley & Sons, Ltd.

Toxicity of oil dispersant, crude oil and dispersed crude oil to a marine amphipod and gastropod

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gulec, I.; Holdway, D.A.

1995-12-31

The importance of appropriate oil spill remedial action was emphasized during the recent Iron Barron oil spill off of the Tamar river in North Tasmania. One important potential oil spill response is dispersion, but little information exists on the toxicity of dispersants and dispersed oil to Australian marine species. This research was undertaken to assess the acute toxicity of Corexit 9527 (a widely used dispersant), water accommodated fractions of Bass Strait crude oil and dispersed Bass Strait crude oil, to the saltwater amphipod, Allorchestes compressa under semi-static conditions. Acute 96 h LC50`s were determined for each toxicant as well asmore » for the reference toxicants sodium dodecyl sulfate (SDS) and zinc sulfate. Sublethal bioassays were undertaken for the same 3 toxicants utilizing the marines and snail Polinices conicus as the test species. No-observed-effect-concentrations (NOEC) and lowest-observed-effect-concentrations (LOEC) were determined using ANOVA while EC50`s and EC0`s were calculated using regression analysis. Mean acute 96 h LC50 (S.E.) values for A. compressa exposed to SDS and zinc sulfate were 3.6 mg/l (0.28) and 41.6 mg/l (9.01) respectively. EC50 (S.E.) concentrations for P. conicus exposed to SDS and zinc sulfate for 30 minutes were 44.7 mg/l and 246 mg/l respectively using burying behavior as an endpoint. These sublethal EC50`s were reduced to 20.7 mg/l for SDS and 23.5 mg/l for zinc sulfate following 24 hours of exposure.« less

A new method to model electroconvulsive therapy in rats with increased construct validity and enhanced translational value.

PubMed

Theilmann, Wiebke; Löscher, Wolfgang; Socala, Katarzyna; Frieling, Helge; Bleich, Stefan; Brandt, Claudia

2014-06-01

Electroconvulsive therapy is the most effective therapy for major depressive disorder (MDD). The remission rate is above 50% in previously pharmacoresistant patients but the mechanisms of action are not fully understood. Electroconvulsive stimulation (ECS) in rodents mimics antidepressant electroconvulsive therapy (ECT) in humans and is widely used to investigate the underlying mechanisms of ECT. For the translational value of findings in animal models it is essential to establish models with the highest construct, face and predictive validity possible. The commonly used model for ECT in rodents does not meet the demand for high construct validity. For ECT, cortical surface electrodes are used to induce therapeutic seizures whereas ECS in rodents is exclusively performed by auricular or corneal electrodes. However, the stimulation site has a major impact on the type and spread of the induced seizure activity and its antidepressant effect. We propose a method in which ECS is performed by screw electrodes placed above the motor cortex of rats to closely simulate the clinical situation and thereby increase the construct validity of the model. Cortical ECS in rats induced reliably seizures comparable to human ECT. Cortical ECS was more effective than auricular ECS to reduce immobility in the forced swim test. Importantly, auricular stimulation had a negative influence on the general health condition of the rats with signs of fear during the stimulation sessions. These results suggest that auricular ECS in rats is not a suitable ECT model. Cortical ECS in rats promises to be a valid method to mimic ECT. Copyright © 2014 Elsevier Ltd. All rights reserved.

Determination and validation of an aquatic Maximum Acceptable Concentration-Environmental Quality Standard (MAC-EQS) value for the agricultural fungicide azoxystrobin.

PubMed

Rodrigues, Elsa Teresa; Pardal, Miguel Ângelo; Gante, Cristiano; Loureiro, João; Lopes, Isabel

2017-02-01

The main goal of the present study was to determine and validate an aquatic Maximum Acceptable Concentration-Environmental Quality Standard (MAC-EQS) value for the agricultural fungicide azoxystrobin (AZX). Assessment factors were applied to short-term toxicity data using the lowest EC 50 and after the Species Sensitivity Distribution (SSD) method. Both ways of EQS generation were applied to a freshwater toxicity dataset for AZX based on available data, and to marine toxicity datasets for AZX and Ortiva ® (a commercial formulation of AZX) obtained by the present study. A high interspecific variability in AZX sensitivity was observed in all datasets, being the copepoda Eudiaptomus graciloides (LC 50,48h  = 38 μg L -1 ) and the gastropod Gibbula umbilicalis (LC 50,96h  = 13 μg L -1 ) the most sensitive freshwater and marine species, respectively. MAC-EQS values derived using the lowest EC 50 (≤0.38 μg L -1 ) were more protective than those derived using the SSD method (≤3.2 μg L -1 ). After comparing the MAC-EQS values estimated in the present study to the smallest AA-EQS available, which protect against the occurrence of prolonged exposure of AZX, the MAC-EQS values derived using the lowest EC 50 were considered overprotective and a MAC-EQS of 1.8 μg L -1 was validated and recommended for AZX for the water column. This value was derived from marine toxicity data, which highlights the importance of testing marine organisms. Moreover, Ortiva affects the most sensitive marine species to a greater extent than AZX, and marine species are more sensitive than freshwater species to AZX. A risk characterization ratio higher than one allowed to conclude that AZX might pose a high risk to the aquatic environment. Also, in a wider conclusion, before new pesticides are approved, we suggest to improve the Tier 1 prospective Ecological Risk Assessment by increasing the number of short-term data, and apply the SSD approach, in order to ensure the safety of aquatic organisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cytogenetic effects of three commercially formulated pesticides on somatic and germ cells of Allium cepa.

PubMed

Kuchy, Aashiq H; Wani, Aijaz A; Kamili, Azra N

2016-04-01

Cytological effects of Endosri-ES (endosulfan), Nuvan-NU (dichlorvos), and Kvistin-KS (carbendazim) were evaluated on mitotic and meiotic cells of Allium cepa. Test concentrations were chosen by calculating EC50 values of formulated ES, NU, and KS, which turned to be 60, 200, and 500 ppm (parts per million), respectively. Cytological studies were undertaken on root meristem cells of A. cepa using EC50, 1/2 × EC50, and 2 × EC50 of these pesticides for 24 and 48 h. Similarly, a meiotic study was conducted by applying the pesticides at the aforesaid concentrations from seedling to bud stage. A set of onion bulbs exposed to tap water was run parallel for negative control and maleic hydrazide (112.09 ppm) as positive control. During the study period, mitotic index (MI) decreased at all the pesticide concentrations compared to the negative control. Among various chromosomal aberrations, chromatin bridges, breaks, stickiness, laggard, vagrant chromosomes, fragments, C-mitosis, multipolarity, ring chromosome as well as micronuclei were observed in mitotic preparations. In contrast, meiotic aberrations revealed comparatively less frequency of chromosomal aberrations and the most frequent were lagging chromosome, stray bivalents, secondary association, chromatin bridge, disturbed anaphase, and stickiness. Comparative analysis of the pesticides showed that NU was highly toxic to plant cells than KS, while as ES showed intermediate effects between the two. Further, our study revealed that all the three pesticides produce genotoxic effects which can cause health risks to the human populations. Graphical Abstract ᅟ.

Influence of dissolved organic carbon on toxicity of copper to a unionid mussel (Villosa iris) and a cladoceran (Ceriodaphnia dubia) in acute and chronic water exposures

USGS Publications Warehouse

Wang, Ning; Mebane, Christopher A.; Kunz, James L.; Ingersoll, Christopher G.; Brumbaugh, William G.; Santore, Robert C.; Gorsuch, Joseph W.; Arnold, W. Ray

2011-01-01

Acute and chronic toxicity of copper (Cu) to a unionid mussel (Villosa iris) and a cladoceran (Ceriodaphnia dubia) were determined in water exposures at four concentrations of dissolved organic carbon (DOC; nominally 0.5, 2.5, 5, and 10 mg/L as carbon [C]). Test waters with DOC concentrations of 2.5 to 10 mg C/L were prepared by mixing a concentrate of natural organic matter (Suwannee River, GA, USA) in diluted well water (hardness 100 mg/L as CaCO3, pH 8.3, DOC 0.5 mg C/L). Acute median effect concentrations (EC50s) for dissolved Cu increased approximately fivefold (15–72 μg Cu/L) for mussel survival in 4-d exposures and increased about 11-fold (25–267 μg Cu/L) for cladoceran survival in 2-d exposures across DOC concentrations from 0.5 to 10 mg C/L. Similarly, chronic 20% effect concentrations (EC20s) for the mussel in 28-d exposures increased about fivefold (13–61 μg Cu/L for survival; 8.8–38 μg Cu/L for biomass), and the EC20s for the cladoceran in 7-d exposures increased approximately 17-fold (13–215 μg Cu/L) for survival or approximately fourfold (12–42 μg Cu/L) for reproduction across DOC concentrations from 0.5 to 10 mg C/L. The acute and chronic values for the mussel were less than or approximately equal to the values for the cladoceran. Predictions from the biotic ligand model (BLM) used to derive the U.S. Environmental Protection Agency's ambient water quality criteria (AWQC) for Cu explained more than 90% of the variation in the acute and chronic endpoints for the two species, with the exception of the EC20 for cladoceran reproduction (only 46% of variation explained). The BLM-normalized acute EC50s and chronic EC20s for the mussel and BLM-normalized chronic EC20s for the cladoceran in waters with DOC concentrations of 2.5 to 10 mg C/L were equal to or less than the final acute value and final chronic value in the BLM-based AWQC for Cu, respectively, indicating that the Cu AWQC might not adequately protect the mussel from acute and chronic exposure, and the cladoceran from chronic exposure.

Chiral recognition of pinacidil and its 3-pyridyl isomer by canine cardiac and smooth muscle: Antagonism by sulfonylureas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steinberg, M.I.; Wiest, S.A.; Zimmerman, K.M.

1991-01-01

Pinacidil, a potassium channel opener (PCO), relaxes vascular smooth muscle by increasing potassium ion membrane conductance, thereby causing membrane hyperpolarization. PCOs also act on cardiac muscle to decrease action potential duration (APD) selectively. To examine the enantiomeric selectivity of pinacidil, the stereoisomers of pinacidil (a 4-pyridylcyanoguanidine) and its 3-pyridyl isomer (LY222675) were synthesized and studied in canine Purkinje fibers and cephalic veins. The (-)-enantiomers of both pinacidil and LY222675 were more potent in relaxing phenylephrine-contracted cephalic veins and decreasing APD than were their corresponding (+)-enantiomers. The EC50 values for (-)-pinacidil and (-)-LY222675 in relaxing cephalic veins were 0.44 and 0.09more » microM, respectively. In decreasing APD, the EC50 values were 3.2 microM for (-)-pinacidil and 0.43 microM for (-)-LY222675. The eudismic ratio was greater for the 3-pyridyl isomer than for pinacidil in both cardiac (71 vs. 22) and vascular (53 vs. 17) tissues. (-)-LY222675 and (-)-pinacidil (0.1-30 microM) also increased 86Rb efflux from cephalic veins to a greater extent than did their respective optical antipodes. The antidiabetic sulfonylurea, glyburide (1-30 microM), shifted the vascular concentration-response curve of (-)-pinacidil to the right by a similar extent at each inhibitor concentration. Glipizide also antagonized the response to (-)-pinacidil, but was about 1/10 as potent with a maximal shift occurring at 10 and 30 microM. Glyburide antagonized the vascular relaxant effects of 0.3 microM (-)-LY222675 (EC50, 2.3 microM) and reversed the decrease in APD caused by 3 microM (-)-LY222675 (EC50, 1.9 microM). Nitroprusside did not alter 86Rb efflux, and vascular relaxation induced by sodium nitroprusside was unaffected by sulfonylureas.« less

Results from a round robin test for the ecotoxicological evaluation of construction products using two leaching tests and an aquatic test battery.

PubMed

Gartiser, Stefan; Heisterkamp, Ines; Schoknecht, Ute; Burkhardt, Michael; Ratte, Monika; Ilvonen, Outi; Brauer, Frank; Brückmann, Jan; Dabrunz, André; Egeler, Philipp; Eisl, Andrea-Maria; Feiler, Ute; Fritz, Ines; König, Sabina; Lebertz, Herbert; Pandard, Pascal; Pötschke, Gabriele; Scheerbaum, Dirk; Schreiber, Frank; Soldán, Přemysl; Weiß, Roland; Weltens, Reinhilde

2017-05-01

A European round robin test according to ISO 5725-2 was conceptually prepared, realised, and evaluated. The aim was to determine the inter-laboratory variability of the overall process for the ecotoxicological characterization of construction products in eluates and bioassays. To this end, two construction products BAM-G1 (granulate) and HSR-2 (roof sealing sheet), both made of EPDM polymers (rubber), were selected. The granular construction product was eluted in a one stage batch test, the planar product in the Dynamic Surface Leaching test (DSLT). A total of 17 laboratories from 5 countries participated in the round robin test: Germany (12), Austria (2), Belgium (1), Czech Republic (1) and France (1). A test battery of four standardised ecotoxicity tests with algae, daphnia, luminescent bacteria and zebrafish eggs was used. As toxicity measures, EC50 and LID values were calculated. All tests, except the fish egg test, were basically able to demonstrate toxic effects and the level of toxicity. The reproducibility of test results depended on the test specimens and the test organisms. Generally, the variability of the EC50 or LID values increased with the overall level of toxicity. For the very toxic BAM-G1 eluate a relative high variability of CV = 73%-110% was observed for EC50 in all biotests, while for the less toxic HSR-2 eluate the reproducibility of EC50 varied with sensitivity: it was very good (CV = 9.3%) for the daphnia test with the lowest sensitivity, followed by the algae test (CV = 36.4%). The luminescent bacteria test, being the most sensitive bioassay for HSR-2 Eluate, showed the highest variability (CV = 74.8%). When considering the complex overall process the reproducibility of bioassays with eluates from construction products was acceptable. Copyright © 2017. Published by Elsevier Ltd.

Influence of pH on the acute toxicity of ammonia to juvenile freshwater mussels (fatmucket, Lampsills siliquoidea)

USGS Publications Warehouse

Wang, N.; Erickson, R.J.; Ingersoll, C.G.; Ivey, C.D.; Brunson, E.L.; Augspurger, T.; Barnhart, M.C.

2008-01-01

The objective of the present study was to evaluate the influence of pH on the toxicity of ammonia to juvenile freshwater mussels. Acute 96-h ammonia toxicity tests were conducted with 10-d-old juvenile mussels (fatmucket, Lampsilis siliquoidea) at five pH levels ranging from 6.5 to 9.0 in flow-through diluter systems at 20??C. Acute 48-h tests with amphipods (Hyalella azteca) and 96-h tests with oligochaetes (Lumbriculus variegatus) were conducted concurrently under the same test conditions to determine the sensitivity of mussels relative to these two commonly tested benthic invertebrate species. During the exposure, pH levels were maintained within 0.1 of a pH unit and ammonia concentrations were relatively constant through time (coefficient of variation for ammonia concentrations ranged from 2 to 30% with a median value of 7.9%). The median effective concentrations (EC50s) of total ammonia nitrogen (N) for mussels were at least two to six times lower than the EC50s for amphipods and oligochaetes, and the EC50s for mussels decreased with increasing pH and ranged from 88 mg N/L at pH 6.6 to 0.96 mg N/L at pH 9.0. The EC50s for mussels were at or below the final acute values used to derive the U.S. Environmental Protection Agency's acute water quality criterion (WQC). However, the quantitative relationship between pH and ammonia toxicity to juvenile mussels was similar to the average relationship for other taxa reported in the WQC. These results indicate that including mussel toxicity data in a revision to the WQC would lower the acute criterion but not change the WQC mathematical representation of the relative effect of pH on ammonia toxicity. ?? 2008 SETAC.

[Photometric micro-titration model of DPPH radicals scavenging activity and its application].

PubMed

Gao, Yun-tao; Wei, Wei; Ye, Li-qing; Li, Xiao-fen; Liu, Ping; Zhang, Hong-jiao; Yang, Lu; Yu, Jiao-jiao; Cha, Jia-wei

2015-02-01

In the present paper, the stoichiometric ratio (R) for the interreaction of DPPH radicals with the antoxidant was employed as a evaluation index for DPPH radicals scavenging activity of antioxidants. This evaluation index was related only with the stoichiometric relationship between DPPH radicals and the antioxidant, not the relationship with the initial DPPH amount and the volume of sample, which could offer a solution for the problem of poor comparability of EC50 under different conditions. A novel photometric micro-titration method was proposed for the determination of the stoichiometric ratio (R) for the interreaction of DPPH radicals with the antoxidant. The titration equation was established based on the absorbance difference (deltaA) of DPPH radicals in the titration process and the added amount of antoxidant. The stoichiometric ratio (R) for the reaction of DPPH radicals with the addition amount of antoxidant was determined by the titration equation obtained, while, the DPPH median elimination concentration (EC50) of antoxidant can be calculated by the stoichiometric ratio (R). The above photometric micro-titration model was verified using rutin as DPPH radicals scavenger. As experiment results, the stoichiometric ratio (R) of DPPH radicals to rutin was determined to be in the range of 1.817-1.846. The calculated value of EC50 was 1.196 x 10(-3), 2.392 x 10(-3), 4.819 x 10(-3) and 7.292 x 10(-3) mg x mL(-1) for 1.12 x 10(-7), 2.24 x 10(-7), 4.48 x 10(-7) and 6.72 x 10(-7) mol of the additon amount of DPPH radicals, respectively. The proposed method has better precision and reliability with smaller amount of sample than conventional method. While, the obtained stoichiometric ratio value (R) of rutin was employed to calculate the rutin median elimination concentration for DPPH EC50) according to the conditions as reported in the literatures, and the calculated results were consistent with that reported in the literatures.

Bioluminescence inhibition assays for toxicity screening of wood extractives and biocides in paper mill process waters.

PubMed

Rigol, Anna; Latorre, Anna; Lacorte, Sílvia; Barceló, Damià

2004-02-01

The risk associated with wood extractives, biocides, and other additives in pulp and paper mill effluents was evaluated by performing a characterization of process waters and effluents in terms of toxicity and chemical analysis. The individual toxicity of 10 resin acids, two unsaturated fatty acids, and three biocides was estimated by measuring the bioluminescence inhibition with a ToxAlert 100 system. Median effective concentration values (EC50) of 4.3 to 17.9, 1.2 to 1.5, and 0.022 to 0.50 mg/L were obtained, respectively. Mixtures of these three families of compounds showed antagonistic effects. Chemical analysis of process waters was performed by liquid chromatography- and gas chromatography-mass spectrometry. Biocides such as 2-(thiocyanomethylthio)-benzotiazole (TCMTB) (EC50 = 0.022 mg/L) and 2,2-dibromo-3-nitrilpropionamide (DBNPA) (EC50 = 0.50 mg/L) were the most toxic compounds tested and were detected at concentrations of 16 and 59 microg/L, respectively, in a closed-circuit recycling paper mill. Process waters from kraft pulp mills, printing paper mills, and packing board paper mills showed the highest concentration of resin acids (up to 400 microg/L) and accounted for inhibition percentages up to 100%. Detergent degradation products such as nonylphenol (NP) and octylphenol (OP) and the plasticizer bisphenol A (BPA) were also detected in the waters at levels of 0.6 to 10.6, 0.3 to 1.4, and 0.7 to 187 microg/L, respectively. However, once these waters were biologically treated, the concentration of detected organic compounds diminished and the toxicity decreased in most cases to values of inhibition lower than 20%.

Comprehensive characterization of the acute and chronic toxicity of the neonicotinoid insecticide thiamethoxam to a suite of aquatic primary producers, invertebrates, and fish.

PubMed

Finnegan, Meaghean C; Baxter, Leilan R; Maul, Jonathan D; Hanson, Mark L; Hoekstra, Paul F

2017-10-01

Thiamethoxam is a neonicotinoid insecticide used widely in agriculture to control a broad spectrum of chewing and sucking insect pests. Recent detection of thiamethoxam in surface waters has raised interest in characterizing the potential impacts of this insecticide to aquatic organisms. We report the results of toxicity testing (acute and chronic) conducted under good laboratory practices for more than 30 freshwater species (insects, molluscs, crustaceans, algae, macrophytes, and fish) and 4 marine species (an alga, a mollusc, a crustacean, and a fish). As would be anticipated for a neonicotinoid, aquatic primary producers and fish were the least sensitive organisms tested, with acute median lethal and effect concentrations (LC50/EC50) observed to be ≥80 mg/L in all cases, which far exceeds surface water exposure concentrations. Tested molluscs, worms, and rotifers were similarly insensitive (EC50 ≥ 100 mg/L), except for Lumbriculus sp., with an EC50 of 7.7 mg/L. In general, insects were the most sensitive group in the study, with most acute EC50 values < 1 mg/L. However, the crustaceans Asellus aquaticus and Ostracoda exhibited a sensitivity similar to that of insects (acute EC50 < 1 mg/L), and the midge larvae Chaoborus sp. were relatively insensitive compared with other insects (EC50 > 5.5 mg/L). The most sensitive chronic response was for Chironomus riparius, with a 30-d no-observed-effect concentration (NOEC; emergence) of 0.01 mg/L. Observed toxicity to the tested marine organisms was comparable to that of freshwater species. We used the reported data to construct species sensitivity distributions for thiamethoxam, to calculate 5% hazard concentrations (HC5s) for acute data (freshwater invertebrates), and compared these with measured concentrations from relevant North American surface waters. Overall, based on acute toxicity endpoints, the potential acute risk to freshwater organisms was found to be minimal (likelihood of exceeding HC5s < 1%). Environ Toxicol Chem 2017;36:2838-2848. © 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. © 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc.

Inhibitory action on the production of advanced glycation end products (AGEs) and suppression of free radicals in vitro by a Sri Lankan polyherbal formulation Nawarathne Kalka.

PubMed

Fernando, Chamira Dilanka; Karunaratne, Diyathi Tharindhi; Gunasinghe, Sachith Dilshan; Cooray, M C Dilusha; Kanchana, Prabuddhi; Udawatte, Chandani; Perera, Pathirage Kamal

2016-07-08

Advanced glycation end products (AGEs) and free radicals are inflammatory mediators and are implicated in many diseases such as diabetes, cancer, rheumatoid arthritis etc. Multi targeted poly herbal drug systems like Nawarathne Kalka (NK) are able to quench the overall effect of these mediators as they contain good combinations of phytochemicals that have least side effects in contrast to modern medicinal drugs. The objectives of this study were to evaluate phytochemical composition, free radical scavenging activity, cytotoxicity and the inhibitory action on the formation of AGEs by aqueous extract of NK. Total phenolic content (TPC) and total flavonoid content (TFC) were determined using Folin ciocalteu method and aluminium chloride assay respectively. Free radical scavenging activity was assessed by DPPH radical scavenging assay (DRSA), phosphomolybdenum reduction antioxidant assay (PRAA) and nitric oxide (NO) scavenging assay. Brine Shrimp Lethality (BSL) bioassay was performed as preliminary screening for cytotoxic activity. Inhibitory action on AGE formation was evaluated using fructose mediated glycation of bovine serum albumin using fluorescence spectroscopic method. The TPC and TFC were 75.1 ± 3.0 mg/g gallic acid equivalents and 68.7 ± 7.8 mg/g epigallocatechin gallate equivalents. The DRSA yielded EC50 of 19.15 ± 2.24 μg mL(-1) for NK. DRSA of NK extract was greater than butylated hydroxy toluene (EC50 = 96.50 ± 4.51 μg mL(-1)) but lesser than L-ascorbic acid (EC50 = 5.60 ± 0.51 μg mL(-1)). The total antioxidant capacity of NK as evidenced by PRAA was 106.4 ± 8.2 mg/g L-ascorbic acid equivalents. NK showed EC50 value of 99.3 ± 8.4 μg mL(-1) in the NO scavenging assay compared to the standard ascorbic acid (EC50 = 7.3 ± 0.3 μg mL(-1)). The extract indicated moderate cytotoxic activity in the BSL bioassay. The extract showed effective inhibitory action on the formation of AGEs with EC50 values of 116 ± 19 μg mL(-1), 125 ± 35 μg mL(-1) and 84 ± 28 μg mL(-1) in data obtained over three consecutive weeks respectively. Comparatively the reference standard, aminoguanidine at a concentration of 500 μg mL(-1) demonstrated 65 % inhibition on the formation of AGE after one week of sample incubation. The results proved the potential of NK as a free radical scavenger, moderate cytotoxic agent and an inhibitor on the formation of advanced glycation end-products.

Evaluation of acute copper toxicity to juvenile freshwater mussels (fatmucket, lampsilis siliquoidea) in natural and reconstituted waters

USGS Publications Warehouse

Wang, N.; Mebane, C.A.; Kunz, J.L.; Ingersoll, C.G.; May, T.W.; Arnold, W.R.; Santore, R.C.; Augspurger, T.; Dwyer, F.J.; Barniiart, M.C.

2009-01-01

The influence of dissolved organic carbon (DOC) and water composition on the toxicity of copper to juvenile freshwater mussels (fatmucket, Lampsilis siliquoidea) were evaluated in natural and reconstituted waters. Acute 96-h copper toxicity tests were conducted at four nominal DOC concentrations (0, 2.5, 5, and 10 mg/L as carbon [C]) in dilutions of natural waters and in American Society for Testing and Materials (ASTM) reconstituted hard water. Toxicity tests also were conducted in ASTM soft, moderately hard, hard, and very hard reconstituted waters (nominal hardness 45-300 mg/L as CaCO3). Three natural surface waters (9.5-11 mg/L DOC) were diluted to obtain a series of DOC concentrations with diluted well water, and an extract of natural organic matter and commercial humic acid was mixed with ASTM hard water to prepare a series of DOC concentrations for toxicity testing. Median effective concentrations (EC50s) for dissolved copper varied >40-fold (9.9 to >396 ??g Cu/L) over all 21 treatments in various DOC waters. Within a particular type of DOC water, EC50s increased 5- to 12-fold across DOC concentrations of 0.3 to up to 11 mg C/L. However, EC50s increased by only a factor of 1.4 (21 30 ??g Cu/L) in the four ASTM waters with wide range of water hardness (52-300 mg CaCO 3/L). Predictions from the biotic ligand model (BLM) for copper explained nearly 90% of the variability in EC50s. Nearly 70% of BLM-normalized EC50s for fatmucket tested in natural waters were below the final acute value used to derive the U.S. Environmental Protection Agency acute water quality criterion for copper, indicating that the criterion might not be protective of fatmucket and perhaps other mussel species. ?? 2009 SETAC.

Mathematical modeling improves EC50 estimations from classical dose-response curves.

PubMed

Nyman, Elin; Lindgren, Isa; Lövfors, William; Lundengård, Karin; Cervin, Ida; Sjöström, Theresia Arbring; Altimiras, Jordi; Cedersund, Gunnar

2015-03-01

The β-adrenergic response is impaired in failing hearts. When studying β-adrenergic function in vitro, the half-maximal effective concentration (EC50 ) is an important measure of ligand response. We previously measured the in vitro contraction force response of chicken heart tissue to increasing concentrations of adrenaline, and observed a decreasing response at high concentrations. The classical interpretation of such data is to assume a maximal response before the decrease, and to fit a sigmoid curve to the remaining data to determine EC50 . Instead, we have applied a mathematical modeling approach to interpret the full dose-response curve in a new way. The developed model predicts a non-steady-state caused by a short resting time between increased concentrations of agonist, which affect the dose-response characterization. Therefore, an improved estimate of EC50 may be calculated using steady-state simulations of the model. The model-based estimation of EC50 is further refined using additional time-resolved data to decrease the uncertainty of the prediction. The resulting model-based EC50 (180-525 nm) is higher than the classically interpreted EC50 (46-191 nm). Mathematical modeling thus makes it possible to re-interpret previously obtained datasets, and to make accurate estimates of EC50 even when steady-state measurements are not experimentally feasible. The mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database, and may be accessed at http://jjj.bio.vu.nl/database/nyman. © 2015 FEBS.

Ecotoxicity evaluation of a liquid detergent using the automatic biotest ECOTOX.

PubMed

Azizullah, Azizullah; Richter, Peter; Ullah, Waheed; Ali, Imran; Häder, Donat-Peter

2013-08-01

Synthetic detergents are common pollutants reaching aquatic environments in different ways after usage at homes, institutions and industries. In this study a liquid detergent, used for dish washing, was evaluated for its toxicity during long- and short-term tests using the automatic biotest ECOTOX. Different parameters of Euglena gracilis like motility, swimming velocity, gravitactic orientation, cell compactness and cell growth were used as end points. In short-term experiments, the maximum adverse effects on motility, velocity, cell shape and gravitaxis were observed after 1 h of exposure. With further increase in exposure time to the detergent a slight recovery of these parameters was observed. In long-term experiments, the detergent caused severe disturbances to E. gracilis. Motility, cell growth and cell compactness (shape) with EC50 values of 0.064, 0.18 and 2.05 %, respectively, were found as the most sensitive parameters to detergent stress. There was a slight positive effect on gravitactic orientation at the lowest two concentrations; at higher concentrations of the detergent cells orientation was highly impaired giving EC50 values of 1.75 and 2.52 % for upward swimming and r-value, respectively.

Acute aquatic toxicity of western juniper (Juniperus occidentalis) foliage and Port Orford cedar (Chamaecyparis lawsoniana) heartwood oils.

PubMed

Duringer, Jennifer M; Swan, Laurence R; Walker, Douglas B; Craig, A Morrie

2010-11-01

Recently, interest has developed for using essential oils from Western juniper (Juniperus occidentalis) foliage and Port Orford cedar (Chamaecyparis lawsoniana) heartwood in commercial products such as pest repellents and cosmetics. In order to gauge the relative toxicological risk that these oils pose to freshwater and marine organisms, the acute aquatic toxicity of these oils was evaluated using OPPTS guidelines to the cladoceran Daphnia magna, the rainbow trout Oncorhynchus mykiss and the green alga Selenastrum capricornutum. For western juniper foliage oil, no toxicity was exhibited toward D. magna or O. mykiss, even at 5.0 mg/L (the highest concentration tested and limit of solubility). For toxicity to S. capricornutum using algal cell density, the 72 and 96 h EC50 value was 1.7 mg/L and the no observable effect concentration (NOEC) was 0.63 mg/L. For Port Orford cedar heartwood oil, no toxicity was exhibited toward O. mykiss or S. capricornutum, even at 5.0 mg/L (the highest concentration tested and limit of solubility). The 48-h D. magna EC50 value was 1.9 mg/L; the NOEC values for algal cell density were 1.25 mg/L (72 h) and 0.63 mg/L (96 h). In summary, this study shows that western juniper foliage and Port Orford cedar heartwood oils demonstrate little to no risk to aquatic organisms.

Estimation of the toxicity of sulfadiazine to Daphnia magna using negligible depletion hollow-fiber liquid-phase microextraction independent of ambient pH

NASA Astrophysics Data System (ADS)

Liu, Kailin; Xu, Shiji; Zhang, Minghuan; Kou, Yahong; Zhou, Xiaomao; Luo, Kun; Hu, Lifeng; Liu, Xiangying; Liu, Min; Bai, Lianyang

2016-12-01

The toxicity of ionizable organic compounds to organisms depends on the pH, which therefore affects risk assessments of these compounds. However, there is not a direct chemical method to predict the toxicity of ionizable organic compounds. To determine whether hollow-fiber liquid-phase microextraction (HF-LPME) is applicable for this purpose, a three-phase HF-LPME was used to measure sulfadiazine and estimate its toxicity to Daphnia magna in solutions of different pH. The result indicated that the sulfadiazine concentrations measured by HF-LPME decreased with increasing pH, which is consistent with the decreased toxicity. The concentration immobilize 50% of the daphnids (EC50) in 48 h calculated from nominal concentrations increased from 11.93 to 273.5 mg L-1 as the pH increased from 6.0 to 8.5, and the coefficient of variation (CV) of the EC50 values reached 104.6%. When calculated from the concentrations measured by HF-LPME (pH 12 acceptor phase), the EC50 ranged from 223.4 to 394.6 mg L-1, and the CV decreased to 27.60%, suggesting that the concentrations measured by HF-LPME can be used to estimate the toxicity of sulfadiazine irrespective of the solution pH.

Toxicity of the fluoroquinolone antibiotics enrofloxacin and ciprofloxacin to photoautotrophic aquatic organisms.

PubMed

Ebert, Ina; Bachmann, Jean; Kühnen, Ute; Küster, Anette; Kussatz, Carola; Maletzki, Dirk; Schlüter, Christoph

2011-12-01

The present study investigated the growth inhibition effect of the fluoroquinolone antibiotics enrofloxacin and ciprofloxacin on four photoautotrophic aquatic species: the freshwater microalga Desmodesmus subspicatus, the cyanobacterium Anabaena flos-aquae, the monocotyledonous macrophyte Lemna minor, and the dicotyledonous macrophyte Myriophyllum spicatum. Both antibiotics, which act by inhibiting the bacterial DNA gyrase, demonstrated high toxicity to A. flos-aquae and L. minor and moderate to slight toxicity to D. subspicatus and M. spicatum. The cyanobacterium was the most sensitive species with median effective concentration (EC50) values of 173 and 10.2 µg/L for enrofloxacin and ciprofloxacin, respectively. Lemna minor proved to be similarly sensitive, with EC50 values of 107 and 62.5 µg/L for enrofloxacin and ciprofloxacin, respectively. While enrofloxacin was more toxic to green algae, ciprofloxacin was more toxic to cyanobacteria. Calculated EC50s for D. subspicatus were 5,568 µg/L and >8,042 µg/L for enrofloxacin and ciprofloxacin, respectively. These data, as well as effect data from the literature, were compared with predicted and reported environmental concentrations. For two of the four species, a risk was identified at ciprofloxacin concentrations found in surface waters, sewage treatment plant influents and effluents, as well as in hospital effluents. For ciprofloxacin the results of the present study indicate a risk even at the predicted environmental concentration. In contrast, for enrofloxacin no risk was identified at predicted and measured concentrations. Copyright © 2011 SETAC.

Biofilm formation in Malassezia pachydermatis strains isolated from dogs decreases susceptibility to ketoconazole and itraconazole.

PubMed

Jerzsele, Akos; Gyetvai, Béla; Csere, István; Gálfi, Péter

2014-12-01

Malassezia pachydermatis is a commonly isolated yeast in veterinary dermatology that can produce biofilms in vitro and in vivo, lowering its susceptibility to antimicrobial drugs. The aim of this study was to determine and compare the in vitro susceptibility of planktonic cells and biofilms of M. pachydermatis isolates to ketoconazole and itraconazole. The presence of biofilm formation was confirmed by crystal violet staining and absorbance measurement at 595 nm wavelength, and by a scanning electron microscopy method. Cell viability was determined by the Celltiter 96 Aqueous One solution assay containing a water-soluble tetrazolium compound (MTS) with absorbance measurement at 490 nm. Planktonic cell minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) of ketoconazole and itraconazole were very low: MIC90 and MFC90 were 0.032 and 0.125 μg/ml for ketoconazole, while 0.063 and 0.25 μg/ml for itraconazole, respectively. Also, the half maximal effective concentrations (EC50) of itraconazole were higher for planktonic cells and biofilms compared to ketoconazole. The EC50 values of ketoconazole were 18-169 times higher and those of itraconazole 13-124 times higher for biofilms than for planktonic cells. Biofilm EC50 levels exceeded MICs 103-2060 times for ketoconazole and 84-1400 times for itraconazole. No significant difference was found between these values of the two substances. In conclusion, biofilms of all examined M. pachydermatis strains were much less susceptible to ketoconazole and itraconazole than their planktonic forms.

Hypotensive, vasorelaxant and cardiodepressant activities of the ethanol extract of Sideritis raeseri spp. raeseri Boiss & Heldr.

PubMed

Kitic, D; Brankovic, S; Radenkovic, M; Savikin, K; Zdunic, G; Kocic, B; Velickovic-Radovanovic, R

2012-10-01

Sideritis raeseri spp. raeseri Boiss & Heldr is a native plant from the Mediterranean region that is used due to its medicinal and culinary properties. The aim of this study was to evaluate the effects of ethanol extract of S. raeseri on the blood pressure, vascular and cardiac contractions. Arterial blood pressure was registered directly from the carotid artery in the anaesthetized rabbits. Aortic rings and the spontaneously beating atria were mounted in tissue bath. An intravenous injection of extract of S. raeseri (0.025-7.5 mg/kg) caused a dose dependent decrease of the arterial pressure and heart rate, with EC(50) value of 24.31±3.87 mg/kg and 88.14±7.51 mg/kg, respectively. In aortic preparations precontracted with KCl (80 mM), the extract of S. raeseri (0.005-1.5 mg/ml) elicited a vasodilatator action (EC(50) 0.11±0.008 mg/ml). In spontaneously beating rat atria, the extract of S. raeseri (0.005-1.5 mg/ml) produced decrease of chronotropic and inotropic activity (with EC(50) value of 0.63±0.03 mg/ml and 0.40±0.08 mg/ml). Administration of verapamil induced inhibition of force and rate of the atrial contraction. These results demonstrate that the ethanol extract of Sideritis raeseri spp. raeseri Boiss & Heldr can produce hypotension, vasodilatation, negative chronotropic and inotropic effects.

Vanadium bioavailability and toxicity to soil microorganisms and plants.

PubMed

Larsson, Maja A; Baken, Stijn; Gustafsson, Jon Petter; Hadialhejazi, Golshid; Smolders, Erik

2013-10-01

Vanadium, V, is a redox-sensitive metal that in solution, under aerobic conditions, prevails as the oxyanion vanadate(V). There is little known regarding vanadium toxicity to soil biota, and the present study was set up to determine the toxicity of added vanadate to soil organisms and to investigate the relationship between toxicity and vanadium sorption in soils. Five soils with contrasting properties were spiked with 7 different doses (3.2-3200 mg V kg(-1)) of dissolved vanadate, and toxicity was measured with 2 microbial and 3 plant assays. The median effective concentration (EC50) thresholds of the microbial assays ranged from 28 mg added V kg(-1) to 690 mg added V kg(-1), and the EC50s in the plant assays ranged from 18 mg added V kg(-1) to 510 mg added V kg(-1). The lower thresholds were in the concentration range of the background vanadium in the untreated control soils (15-58 mg V kg(-1)). The vanadium toxicity to plants decreased with a stronger soil vanadium sorption strength. The EC50 values for plants expressed on a soil solution basis ranged from 0.8 mg V L(-1) to 15 mg V L(-1) and were less variable among soils than corresponding values based on total vanadium in soil. It is concluded that sorption decreases the toxicity of added vanadate and that soil solution vanadium is a more robust measure to determine critical vanadium concentrations across soils. © 2013 SETAC.

Design, Synthesis, and Antifouling Activity of Glucosamine-Based Isocyanides.

PubMed

Umezawa, Taiki; Hasegawa, Yuki; Novita, Ira S; Suzuki, Junya; Morozumi, Tatsuya; Nogata, Yasuyuki; Yoshimura, Erina; Matsuda, Fuyuhiko

2017-06-29

Biofouling, an undesirable accumulation of organisms on sea-immersed structures such as ship hulls and fishing nets, is a serious economic issue whose effects include oil wastage and clogged nets. Organotin compounds were utilized since the 1960s as an antifouling material; however, the use of such compounds was later banned by the International Maritime Organization (IMO) due to their high toxicity toward marine organisms, resulting in masculinization and imposex. Since the ban, there have been extensive efforts to develop environmentally benign antifoulants. Natural antifouling products obtained from marine creatures have been the subject of considerable attention due to their potent antifouling activity and low toxicity. These antifouling compounds often contain isocyano groups, which are well known to have natural antifouling properties. On the basis of our previous total synthesis of natural isocyanoterpenoids, we envisaged the installation of an isocyano functional group onto glucosamine to produce an environmentally friendly antifouling material. This paper describes an effective synthetic method for various glucosamine-based isocyanides and evaluation of their antifouling activity and toxicity against cypris larvae of the barnacle Amphibalanus amphitrite . Glucosamine isocyanides with an ether functionality at the anomeric position exhibited potent antifouling activity, with EC 50 values below 1 μg/mL, without detectable toxicity even at a high concentration of 10 μg/mL. Two isocyanides had EC 50 values of 0.23 and 0.25 μg/mL, comparable to that of CuSO₄, which is used as a fouling inhibitor (EC 50 = 0.27 μg/mL).

Effects of a chitin-binding vicilin from Enterolobium contortisiliquum seeds on bean bruchid pests (Callosobruchus maculatus and Zabrotes subfasciatus) and phytopathogenic fungi (Fusarium solani and Colletrichum lindemuntianum).

PubMed

Moura, Fabiano T; Oliveira, Adeliana S; Macedo, Leonardo L P; Vianna, André L B R; Andrade, Lucia B S; Martins-Miranda, A S; Oliveira, Jose T A; Santos, Elizeu A; de Sales, Mauricio P

2007-01-24

Chitin-binding vicilin from Enterolobium contortisiliquum seeds was purified by ammonium sulfate followed by gel filtration on Sephacryl 300-SH and on Sephacryl 200-SH. The vicilin, called EcV, is a dimeric glycoprotein composed of 1.03% carbohydrates and a Mr of 151 kDa, consisting of two subunits of Mr of 66.2 and 63.8 kDa. The EcV homogeneity was confirmed in a PAGE where it was observed to be a unique acid protein band with slow mobility in this native gel. E. contortisiliquum vicilin (EcV) was tested for anti-insect activity against C. maculatus and Zabrotes subfasciatus larvae and for phytopathogenic fungi, F. solani and C. lindemuntianum. EcV was very effective against both bruchids, producing 50% mortality for Z. subfasciatus at an LD50 of 0.43% and affected 50% of the larvae mass with an ED50 of 0.65%. In artificial diets given to C. maculatus, 50% of the larvae mass was affected with an ED50 of 1.03%, and larva mortality was 50% at LD50 of 1.11%. EcV was not digested by midgut homogenates of C. maculatus and Z. Subfasciatus until 12 h of incubation, and at 24 h EcV was more resistant to Z. subfasciatus larval proteases. The binding to chitin present in larvae gut associated to low EcV digestibility could explain its lethal effects. EcV also exerted an inhibitory effect on the germination of F. solani at concentrations of 10 and 20 microg mL-1. The effect of EcV on fungi is possibly due to binding to chitin-containing structures of the fungal cell wall.

Effect of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl} acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function.

PubMed

Takasu, Toshiyuki; Ukai, Masashi; Sato, Shuichi; Matsui, Tetsuo; Nagase, Itsuro; Maruyama, Tatsuya; Sasamata, Masao; Miyata, Keiji; Uchida, Hisashi; Yamaguchi, Osamu

2007-05-01

We evaluated the pharmacological characteristics of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]-ethyl} acetanilide (YM178). YM178 increased cyclic AMP accumulation in Chinese hamster ovary (CHO) cells expressing human beta3-adrenoceptor (AR). The half-maximal effective concentration (EC50) value was 22.4 nM. EC50 values of YM178 for human beta1- and beta2-ARs were 10,000 nM or more, respectively. The ratio of intrinsic activities of YM178 versus maximal response induced by isoproterenol (nonselective beta-AR agonist) was 0.8 for human beta3-ARs, 0.1 for human beta1-ARs, and 0.1 for human beta2-ARs. The relaxant effects of YM178 were evaluated in rats and humans bladder strips precontracted with carbachol (CCh) and compared with those of isoproterenol and 4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (CGP-12177A) (beta3-AR agonist). EC50 values of YM178 and isoproterenol in rat bladder strips precontracted with 10(-6) M CCh were 5.1 and 1.4 microM, respectively, whereas those in human bladder strips precontracted with 10(-7) M CCh were 0.78 and 0.28 microM, respectively. In in vivo study, YM178 at a dose of 3 mg/kg i.v. decreased the frequency of rhythmic bladder contraction induced by intravesical filling with saline without suppressing its amplitude in anesthetized rats. These findings suggest the suitability of YM178 as a therapeutic drug for the treatment of symptoms of overactive bladder such as urinary frequency, urgency, and urge incontinence.

The Impact of Selective-Logging and Forest Clearance for Oil Palm on Fungal Communities in Borneo

PubMed Central

Kerfahi, Dorsaf; Tripathi, Binu M.; Lee, Junghoon; Edwards, David P.; Adams, Jonathan M.

2014-01-01

Tropical forests are being rapidly altered by logging, and cleared for agriculture. Understanding the effects of these land use changes on soil fungi, which play vital roles in the soil ecosystem functioning and services, is a major conservation frontier. Using 454-pyrosequencing of the ITS1 region of extracted soil DNA, we compared communities of soil fungi between unlogged, once-logged, and twice-logged rainforest, and areas cleared for oil palm, in Sabah, Malaysia. Overall fungal community composition differed significantly between forest and oil palm plantation. The OTU richness and Chao 1 were higher in forest, compared to oil palm plantation. As a proportion of total reads, Basidiomycota were more abundant in forest soil, compared to oil palm plantation soil. The turnover of fungal OTUs across space, true β-diversity, was also higher in forest than oil palm plantation. Ectomycorrhizal (EcM) fungal abundance was significantly different between land uses, with highest relative abundance (out of total fungal reads) observed in unlogged forest soil, lower abundance in logged forest, and lowest in oil palm. In their entirety, these results indicate a pervasive effect of conversion to oil palm on fungal community structure. Such wholesale changes in fungal communities might impact the long-term sustainability of oil palm agriculture. Logging also has more subtle long term effects, on relative abundance of EcM fungi, which might affect tree recruitment and nutrient cycling. However, in general the logged forest retains most of the diversity and community composition of unlogged forest. PMID:25405609

The impact of selective-logging and forest clearance for oil palm on fungal communities in Borneo.

PubMed

Kerfahi, Dorsaf; Tripathi, Binu M; Lee, Junghoon; Edwards, David P; Adams, Jonathan M

2014-01-01

Tropical forests are being rapidly altered by logging, and cleared for agriculture. Understanding the effects of these land use changes on soil fungi, which play vital roles in the soil ecosystem functioning and services, is a major conservation frontier. Using 454-pyrosequencing of the ITS1 region of extracted soil DNA, we compared communities of soil fungi between unlogged, once-logged, and twice-logged rainforest, and areas cleared for oil palm, in Sabah, Malaysia. Overall fungal community composition differed significantly between forest and oil palm plantation. The OTU richness and Chao 1 were higher in forest, compared to oil palm plantation. As a proportion of total reads, Basidiomycota were more abundant in forest soil, compared to oil palm plantation soil. The turnover of fungal OTUs across space, true β-diversity, was also higher in forest than oil palm plantation. Ectomycorrhizal (EcM) fungal abundance was significantly different between land uses, with highest relative abundance (out of total fungal reads) observed in unlogged forest soil, lower abundance in logged forest, and lowest in oil palm. In their entirety, these results indicate a pervasive effect of conversion to oil palm on fungal community structure. Such wholesale changes in fungal communities might impact the long-term sustainability of oil palm agriculture. Logging also has more subtle long term effects, on relative abundance of EcM fungi, which might affect tree recruitment and nutrient cycling. However, in general the logged forest retains most of the diversity and community composition of unlogged forest.

A comparative study of functional 5-HT4 receptors in human colon, rat oesophagus and rat ileum.

PubMed

McLean, P G; Coupar, I M; Molenaar, P

1995-05-01

1. The pharmacological properties of 5-hydroxytryptamine (5-HT), the 5-HT4 receptor agonists, DAU 6236 and SC 53116 and the 5-HT4 receptor antagonist, GR 1130808, were studied in the rat oesophagus, rat ileum and human colon. 2. 5-HT relaxed the longitudinal muscle of the rat oesophagus and rat ileum and the circular muscle of the human colon. Absolute values of relaxation were measured and showed the order of the maximum responses, rat oesophagus > human colon > rat ileum with EC50 values of 189 +/- 15 nM, 157 +/- 4 nM, 306 +/- 72 nM, respectively. 5-HT also inhibited the spontaneous contractions of the human colon with an EC50 value of 119 +/- 1 nM. The effect of 5-HT on the human colon was not affected by methysergide (10 microM) or ondansetron (1 microM). 3. The use of the uptake and metabolism inhibitors, cocaine (30 microM) and pargyline (100 microM), did not increase the potency of 5-HT in the rat oesophagus or human colon. In the rat oesophagus, cocaine (30 microM) produced a reduction in carbachol-induced tone of 22.2 +/- 0.6% and reduced the 5-HT maximum effect by 52.0 +/- 0.4%. 4. The compounds, DAU 6236 and SC 53116, showed a different pattern of potencies and efficacies in the rat oesophagus, rat ileum and human colon compared to 5-HT. DAU 6236 relaxed the human colonic circular muscle with an EC50 value of 129 +/- 16 nM but its efficacy was less than that of 5-HT. DAU 6236 (1 microM) also antagonized the 5-HT-induced relaxation of the human colon with a dose-ratio of 9.9. In the rat oesophagus and rat ileum, DAU 6236 was inactive in the majority of tissues. In the minority of oesophagus tissues that did respond the EC50 value was 1.2 +/- 0.7 microM. DAU 6236 also antagonized the effect of 5-HT in the rat oesophagus in a non-surmountable fashion. SC 53116 relaxed the rat oesophagus with an EC50 value of 91 +/- 4 nM, with an efficacy less than that observed to 5-HT; however, at 200 nM it did not antagonize the 5-HT-induced relaxation of the rat oesophagus. SC 53116 showed no agonist activity in the rat ileum and human colon, but at 1 microM it did antagonize the effect of 5-HT in the human colon with a dose-ratio of 11.3 +/- 0.3. 5. GR 113808 competitively antagonized the 5-HT4 receptor-mediated relaxation of the rat oesophagus with a pA2 value of 8.59 (8.18-9.00) against 5-HT and 9.05 (8.79-9.31) against SC 53116. GR 113808(0.01 microM) also antagonized the 5-HT-induced relaxation of human colonic circular muscle with an apparent pA2 value of 9.02 +/- 0.12. However at 1 microM the apparent pA2 value was significantly lower than that measured at 0.01 and 0.1 microM. GR 113808 (0.01 microM) antagonized the 5-HT4 receptor-mediated relaxation of the rat ileum with an apparent pA2 value of 9.30 +/- 0.21.6. In conclusion, these studies have shown that the human colon, rat oesophagus and rat ileum contain functional 5-HT4 receptors. However, the 5-HT4 receptor agonists displayed differences in these tissues making it necessary to be cautious when extrapolating from animal to human tissue. This emphasizes the importance of the use of human tissue in the development of therapeutic drugs.

Antiparasitic Activity and Essential Oil Chemical Analysis of the Piper Tuberculatum Jacq Fruit

PubMed Central

dos Santos Sales, Valterlúcio; Monteiro, Álefe Brito; Delmondes, Gyllyandeson de Araújo; do Nascimento, Emmily Petícia; Sobreira Dantas Nóbrega de Figuêiredo, Francisco Rodolpho; de Souza Rodrigues, Cristina Kelly; Evangelista de Lacerda, Josefa Fernanda; Fernandes, Cícera Norma; Barbosa, Maysa de Oliveira; Brasil, Adamo Xenofonte; Tintino, Saulo Relison; Vega Gomez, Maria Celeste; Coronel, Cathia; Melo Coutinho, Henrique Douglas; Martins da Costa, José Galberto; Bezerra Felipe, Cícero Francisco; Alencar de Menezes, Irwin Rose; Kerntopf, Marta Regina

2018-01-01

With the increase of neglected diseases such as leishmaniasis and Chagas disease, there was a need for the search for new therapeutic alternatives that reduce the harm caused by medicine available for treatment. Thus, this study was performed to investigate the antiparasitic activity of the essential oil from the fruits of Piper tuberculatum Jacq, against lines of Leishmania braziliensis (MHOM/CO/88/UA301), Leishmania infantum (MHOM/ES/92/BCN83) and Trypanosoma cruzi (LC-B5 clone). Before running protocols, an analysis of the chemical composition of essential oil was conducted, which presented monoterpenes and sesquiterpenes. As major constituents, β-pinene and α-pinene were identified. Regarding to antiparasitic activity, the essential oil had an EC50 values of 133.97 µg/mL and 143.59 µg/mL against variations promastigotes of L. infantum and L. braziliensis, respectively. As for trypanocidal activity, the oil showed EC50 value of 140.31 µg/mL against epimastigote form of T. cruzi. Moreover, it showed moderate cytotoxicity in fibroblasts with LC50 value of 204.71 µg/mL. The observed effect may be related to the presence of terpenes contained in the essential oil, since it has its antiparasitic activity proven in the literature.

Preclinical Profile and Characterization of the Hepatitis C Virus NS3 Protease Inhibitor Asunaprevir (BMS-650032)

PubMed Central

Sheaffer, Amy K.; Friborg, Jacques; Hernandez, Dennis; Falk, Paul; Zhai, Guangzhi; Levine, Steven; Chaniewski, Susan; Yu, Fei; Barry, Diana; Chen, Chaoqun; Lee, Min S.; Mosure, Kathy; Sun, Li-Qiang; Sinz, Michael; Meanwell, Nicholas A.; Colonno, Richard J.; Knipe, Jay; Scola, Paul

2012-01-01

Asunaprevir (ASV; BMS-650032) is a hepatitis C virus (HCV) NS3 protease inhibitor that has demonstrated efficacy in patients chronically infected with HCV genotype 1 when combined with alfa interferon and/or the NS5A replication complex inhibitor daclatasvir. ASV competitively binds to the NS3/4A protease complex, with Ki values of 0.4 and 0.24 nM against recombinant enzymes representing genotypes 1a (H77) and 1b (J4L6S), respectively. Selectivity was demonstrated by the absence of any significant activity against the closely related GB virus-B NS3 protease and a panel of human serine or cysteine proteases. In cell culture, ASV inhibited replication of HCV replicons representing genotypes 1 and 4, with 50% effective concentrations (EC50s) ranging from 1 to 4 nM, and had weaker activity against genotypes 2 and 3 (EC50, 67 to 1,162 nM). Selectivity was again demonstrated by the absence of activity (EC50, >12 μM) against a panel of other RNA viruses. ASV exhibited additive or synergistic activity in combination studies with alfa interferon, ribavirin, and/or inhibitors specifically targeting NS5A or NS5B. Plasma and tissue exposures in vivo in several animal species indicated that ASV displayed a hepatotropic disposition (liver-to-plasma ratios ranging from 40- to 359-fold across species). Twenty-four hours postdose, liver exposures across all species tested were ≥110-fold above the inhibitor EC50s observed with HCV genotype-1 replicons. Based on these virologic and exposure properties, ASV holds promise for future utility in a combination with other anti-HCV agents in the treatment of HCV-infected patients. PMID:22869577

The Dual Antimelanogenic and Antioxidant Activities of the Essential Oil Extracted from the Leaves of Acorus macrospadiceus (Yamamoto) F. N. Wei et Y. K. Li

PubMed Central

Huang, Huey-Chun; Wang, Hsiao-Fen; Yih, Kuang-Hway; Chang, Long-Zen; Chang, Tsong-Min

2012-01-01

The antimelanogenic and antioxidant activities of the essential oil extracted from the leaves of Acorus macrospadiceus (Yamamoto) F. N. Wei et Y. K. Li have never been explored. The essential oil effectively inhibited mushroom tyrosinase activity (EC50 = 1.57 mg/mL) and B16F10 tyrosinase activity (IC50 = 1.01 mg/mL), decreased the melanin content (EC50 = 1.04 mg/mL), and depleted the cellular level of the reactive oxygen species (ROS) (EC50 = 1.87 mg/mL). The essential oil effectively scavenged 2,2-diphenyl-1-picryl-hydrazyl (DPPH) (EC50 = 0.121 mg/mL) and 2,2′-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) ABTS+ radicals (EC50 = 0.122 mg/mL). It also exhibited an apparent reducing power (EC50 = 0.021 mg/mL) and metal-ion chelating activity (EC50 = 0.029 mg/mL). The chemical constituents of the essential oil are ethers (55.73%), ketones (19.57%), monoterpenes (7.82%), alcohols (3.85%), esters (3.77%), sesquiterpenes (3.72%), and aromatic compounds (2.85%). The results confirm that A. macrospadiceus essential oil is a natural antioxidant and inhibitor of melanogenesis. PMID:23304214

Biotechnological potential of endophytic actinomycetes associated with Asteraceae plants: isolation, biodiversity and bioactivities.

PubMed

Tanvir, Rabia; Sajid, Imran; Hasnain, Shahida

2014-04-01

Endophytic actinomycetes from five Asteraceae plants were isolated and evaluated for their bioactivities. From Parthenium hysterophorus, Ageratum conyzoides, Sonchus oleraceus, Sonchus asper and Hieracium canadense, 42, 45, 90, 3, and 2 isolates, respectively, were obtained. Of the isolates, 86 (47.2 %) showed antimicrobial activity. Majority of the isolates were recovered from the roots (n = 127, 69.7 %). The dominant genus was Streptomyces (n = 96, 52.7 %), while Amycolatopsis, Pseudonocardia, Nocardia and Micromonospora were also recovered. Overall, 36 of the 86 isolates were significantly bioactivity while 18 (20.9 %) showed strong bioactivity. In total, 52.1 and 66.6 % showed potent cytotoxicity and antioxidant activities. The LC50 for 15 strains was <20 μg/ml. Compared to the ascorbate standard (EC50 0.34 μg/ml), all isolates gave impressive results with notable EC50 values of 0.65, 0.67, 0.74 and 0.79 μg/ml.

Aldosterone sensitizes connecting tubule glomerular feedback via the aldosterone receptor GPR30

PubMed Central

Ren, YiLin; D'Ambrosio, Martin A.; Garvin, Jeffrey L.; Leung, Pablo; Kutskill, Kristopher; Wang, Hong; Peterson, Edward L.

2014-01-01

Increasing Na delivery to epithelial Na channels (ENaC) in the connecting tubule (CNT) dilates the afferent arteriole (Af-Art), a process we call connecting tubule glomerular feedback (CTGF). We hypothesize that aldosterone sensitizes CTGF via a nongenomic mechanism that stimulates CNT ENaC via the aldosterone receptor GPR30. Rabbit Af-Arts and their adherent CNTs were microdissected and simultaneously perfused. Two consecutive CTGF curves were elicited by increasing luminal NaCl in the CNT. During the control period, the concentration of NaCl that elicited a half-maximal response (EC50) was 37.0 ± 2.0 mmol/l; addition of aldosterone 10−8 mol/l to the CNT lumen caused a left-shift (decrease) in EC50 to 19.3 ± 1.3 mmol/l (P = 0.001 vs. control; n = 6). Neither the transcription inhibitor actinomycin D nor the translation inhibitor cycloheximide prevented the effect of aldosterone (control EC50 = 34.7 ± 1.9 mmol/l; aldosterone+actinomycin D EC50 = 22.6 ± 1.6 mmol/l; P < 0.001 and control EC50 = 32.4 ± 4.3 mmol/l; aldosterone+cycloheximide EC50 = 17.4 ± 3.3 mmol/l; P < 0.001). The aldosterone antagonist eplerenone prevented the sensitization of CTGF by aldosterone (control EC50 = 33.2 ± 1.7 mmol/l; aldosterone+eplerenone EC50 = 33.5 ± 1.3 mmol/l; n = 7). The GPR30 receptor blocker G-36 blocked the sensitization of CTGF by aldosterone (aldosterone EC50 = 16.5 ± 1.9 mmol/l; aldosterone+G-36 EC50 = 29.0 ± 2.1 mmol/l; n = 7; P < 0.001). Finally, we found that the sensitization of CTGF by aldosterone was mediated, at least in part, by the sodium/hydrogen exchanger (NHE). We conclude that aldosterone in the CNT lumen sensitizes CTGF via a nongenomic effect involving GPR30 receptors and NHE. Sensitized CTGF induced by aldosterone may contribute to renal damage by increasing Af-Art dilation and glomerular capillary pressure (glomerular barotrauma). PMID:24966088

Alpha 1 adrenergic receptor mediated polyphosphoinositide breakdown in DDT1-MF2 cells. Lack of evidence of desensitization after prolonged exposure to epinephrine.

PubMed

Rosenbaum, J S; Azhar, S; Hoffman, B B

1987-12-15

The DDT1-MF2 cell line is a transformed smooth muscle cell line which is known to possess both alpha 1 and beta 2 adrenergic receptors. We have utilized these cells to compare the effects of epinephrine pretreatment on the functional capabilities of these two different adrenergic receptors. Pretreatment of the cells grown in suspension with 10(-7) M epinephrine for 6 hr resulted in desensitization of beta receptor stimulated cyclic AMP accumulation. The maximal response to isoproterenol was decreased to 46 +/- 6% of the value in controls (P less than 0.05); there was also a decrease in the sensitivity of the cells to isoproterenol (log EC50 = -6.65 +/- 0.22 vs -7.26 +/- 0.11 in controls, P less than 0.05). Also, there was a decrease in the number of beta receptors from 257 +/- 29 to 163 +/- 22 fmol/mg protein. In contrast, pretreatment with 10(-6) M epinephrine for 6 hr failed to induce a loss of sensitivity in the ability of the alpha 1 receptor agonist phenylephrine to stimulate inositol triphosphate accumulation (log EC50 = -5.59 +/- 0.18 vs -5.42 +/- 0.44 in control cells). A 2-fold increase in basal inositol monophosphate accumulation was observed after epinephrine pretreatment (P less than 0.05); however, there was no change in maximal phenylephrine-stimulated inositol monophosphate accumulation in these cells. There was a small decrease in the alpha 1 receptor number after epinephrine pretreatment (Bmax = 457 +/- 89 fmol/mg protein vs 540 +/- 94 in control cells, P less than 0.05). In contrast to epinephrine pretreatment, pretreatment of cells in suspension with 10(-7) M 12-O-tetradecanoylphorbol-13-acetate (TPA) for 15 min resulted in a nearly complete blunting in the ability of both norepinephrine and phenylephrine to stimulate inositol phosphate accumulation: after norepinephrine stimulation, 774 +/- 34 dpm in TPA-pretreated cells vs 2590 +/- 10 in control cells; inositol monophosphate accumulation after phenylephrine stimulation 576 +/- 25 dpm in TPA-pretreated cells vs 1660 +/- 27 in control cells. Basal levels of inositol monophosphate remained unchanged at 544 +/- 28 dpm vs 505 +/- 31 in TPA-pretreated cells compared to control cells. These data indicate that protein kinase C may exert a negative feedback control on the alpha 1 receptor in these cells and that direct activation of protein kinase C by phorbol esters may have a different effect on the alpha 1 adrenergic receptor system in DDT1-MF2 cells than does prolonged exposure to epinephrine.

Coumarins from the Herb Cnidium monnieri and Chemically Modified Derivatives as Antifoulants against Balanus albicostatus and Bugula neritina Larvae

PubMed Central

Wang, Zhan-Chang; Feng, Dan-Qing; Ke, Cai-Huan

2013-01-01

In the search for new environmental friendly antifouling (AF) agents, four coumarins were isolated from the herbal plant Cnidium monnieri, known as osthole (1), imperatorin (2), isopimpinellin (3) and auraptenol (4). Furthermore, five coumarin derivatives, namely 8-epoxypentylcoumarin (5), meranzin hydrate (6), 2′-deoxymetranzin hydrate (7), 8-methylbutenalcoumarin (8), and micromarin-F (9) were synthesized from osthole. Compounds 1, 2, 4, 7 showed high inhibitory activities against larval settlement of Balanus albicostatus with EC50 values of 4.64, 3.39, 3.38, 4.67 μg mL−1. Compound 8 could significantly inhibit larval settlement of Bugula neritina with an EC50 value of 3.87 μg mL−1. The impact of functional groups on anti-larval settlement activities suggested that the groups on C-5′ and C-2′/C-3′ of isoamylene chian could affect the AF activities. PMID:23303279

Ecotoxicological characterization of hazardous wastes.

PubMed

Wilke, B-M; Riepert, F; Koch, Christine; Kühne, T

2008-06-01

In Europe hazardous wastes are classified by 14 criteria including ecotoxicity (H 14). Standardized methods originally developed for chemical and soil testing were adapted for the ecotoxicological characterization of wastes including leachate and solid phase tests. A consensus on which tests should be recommended as mandatory is still missing. Up to now, only a guidance on how to proceed with the preparation of waste materials has been standardized by CEN as EN 14735. In this study, tests including higher plants, earthworms, collembolans, microorganisms, duckweed and luminescent bacteria were selected to characterize the ecotoxicological potential of a boiler slag, a dried sewage sludge, a thin sludge and a waste petrol. In general, the instructions given in EN 14735 were suitable for all wastes used. The evaluation of the different test systems by determining the LC/EC(50) or NOEC-values revealed that the collembolan reproduction and the duckweed frond numbers were the most sensitive endpoints. For a final classification and ranking of wastes the Toxicity Classification System (TCS) using EC/LC(50) values seems to be appropriate.

The oxidative stress response of myclobutanil and cyproconazole on Tetrahymena thermophila.

PubMed

Huang, Ai-Guo; Tu, Xiao; Liu, Lei; Wang, Gao-Xue; Ling, Fei

2016-01-01

Using Tetrahymena thermophila as experimental models, the oxidative stress of triazole fungicides myclobutanil (MYC) and cyproconazole (CYP) was investigated. Results showed that 24-h EC50 values for MYC and CYP were 16.67 (13.37-19.65) and 20.44 (18.85-21.96) mg/L, respectively; 48-h EC50 values for MYC and CYP were 14.31 (13.13-15.42) and 18.76 (17.09-20.31) mg/L, respectively. Reactive oxygen species was significantly induced and cytotoxicity was caused by MYC and CYP by increasing propidium iodide (PI) fluorescence. Damage of regular wrinkles and appearing of small holes on the cell surface were observed by SEM. Furthermore, MYC and CYP also caused notable changes in enzyme activities and mRNA levels. Overall, the present study points out that MYC and CYP lead to oxidative stress on T. thermophila. The information presented in this study will provide insights into the mechanism of triazoles-induced oxidative stress on T. thermophila. Copyright © 2015 Elsevier B.V. All rights reserved.

Radon emanation of heterogeneous basin deposits in Kathmandu Valley, Nepal

NASA Astrophysics Data System (ADS)

Girault, Frédéric; Gajurel, Ananta Prasad; Perrier, Frédéric; Upreti, Bishal Nath; Richon, Patrick

2011-01-01

Effective radium-226 concentration ( EC Ra) has been measured in soil samples from seven horizontal and vertical profiles of terrace scarps in the northern part of Kathmandu Valley, Nepal. The samples belong to the Thimi, Gokarna, and Tokha Formations, dated from 50 to 14 ky BP, and represent a diverse fluvio-deltaic sedimentary facies mainly consisting of gravelly to coarse sands, black, orange and brown clays. EC Ra was measured in the laboratory by radon-222 emanation. The samples ( n = 177) are placed in air-tight glass containers, from which, after an accumulation time varying from 3 to 18 days, the concentration of radon-222, radioactive decay product of radium-226 and radioactive gas with a half-life of 3.8 days, is measured using scintillation flasks. The EC Ra values from the seven different profiles of the terrace deposits vary from 0.4 to 43 Bq kg -1, with profile averages ranging from 12 ± 1 to 27 ± 2 Bq kg -1. The values have a remarkable consistency along a particular horizon of sediment layers, clearly demonstrating that these values can be used for long distance correlations of the sediment horizons. Widely separated sediment profiles, representing similar stratigraphic positions, exhibit consistent EC Ra values in corresponding stratigraphic sediment layers. EC Ra measurements therefore appear particularly useful for lithologic and stratigraphic discriminations. For comparison, EC Ra values of soils from different localities having various sources of origin were also obtained: 9.2 ± 0.4 Bq kg -1 in soils of Syabru-Bensi (Central Nepal), 23 ± 1 Bq kg -1 in red residual soils of the Bhattar-Trisuli Bazar terrace (North of Kathmandu), 17.1 ± 0.3 Bq kg -1 in red residual soils of terrace of Kalikasthan (North of Trisuli Bazar) and 10 ± 1 Bq kg -1 in red residual soils of a site near Nagarkot (East of Kathmandu). The knowledge of EC Ra values for these various soils is important for modelling radon exhalation at the ground surface, in particular in the vicinity of active faults. Importantly, the study also reveals that, above numerous sediments of Kathmandu Valley, radon concentration in dwellings can potentially exceed the level of 300 Bq m -3 for residential areas; a fact that should be seriously taken into account by the governmental and non-governmental agencies as well as building authorities.

Degradation and ecotoxicity of dye Reactive Black 5 after reductive-oxidative process : Environmental Science and Pollution Research.

PubMed

Cuervo Lumbaque, Elisabeth; Gomes, Monike Felipe; Da Silva Carvalho, Vanessa; de Freitas, Adriane Martins; Tiburtius, Elaine Regina Lopes

2017-03-01

This research paper describes the study of a reduction-oxidation system using commercial steel wool (Fe 0 ) and H 2 O 2 for degradation of the dye Reactive Black 5 and aromatic compounds in water. The reductive process alone allowed the almost complete removal of color (97 ± 1 %) after 60 min of reaction. The decrease in spectral area (λ = 599 nm) associated with the chromophore group indicates breakage of the azo bonds. Moreover, the significant change in UV spectra can be associated with the formation of aromatic amines. Regarding the transformation products, a spectrophotometric method based on the diazotization reaction was employed to identify aromatic amines after reductive process, using sulfanilic acid as a model of aromatic amines. In addition, association with Fenton reagents improved the efficiency in the system with 93 ± 1 % degradation of intermediates formed during the reductive process. Ecotoxicological analysis revealed that the dye solution, after the reductive and oxidative processes, was not toxic to Lactuca sativa seeds. For Daphnia magna, the EC 50 (%) values observed revealed that dye solution has an EC 50 (%) = 74.1 and after reductive process, the toxicity increased (EC 50 (%) = 63.5), which might be related to the formation of aromatic amines. However, after the Fenton process, the EC 50 (%) was >100. These results demonstrated that the Fenton reaction using steel wool as an iron source was very efficient to decrease color, aromatic transformation products, and the ecotoxicity of Reactive Black 5 in solution.

Two Novel Antioxidant Nonapeptides from Protein Hydrolysate of Skate (Raja porosa) Muscle

PubMed Central

Hu, Fa-Yuan; Chi, Chang-Feng; Wang, Bin; Deng, Shang-Gui

2015-01-01

In the current study, the preparation conditions of neutrase hydrolysate (SMH) from skate (Raja porosa) muscle protein were optimized using orthogonal L9(3)4 tests, and R values indicated that pH was the most important factor affecting HO· scavenging activity of SMH. Under the optimum conditions of pH 7.0, enzymolysis temperature 60 °C, enzyme/substrate ratio (E/S) 2%, and enzymolysis time 5 h, EC50 of SMH on HO· was 2.14 ± 0.17 mg/mL. Using ultrafiltration, gel filtration chromatography, and RP-HPLC, two novel antioxidant nonapeptides (SP-A and SP-B) were isolated from SMH and their amino acid sequences were found to be APPTAYAQS (SP-A) and NWDMEKIWD (SP-B) with calculated molecular masses of 904.98 Da and 1236.38 Da, respectively. Both showed strong antioxidant activities. SP-A and SP-B exhibited good scavenging activities on HO· (EC50 0.390 and 0.176 mg/mL), DPPH· (EC50 0.614 and 0.289 mg/mL), and O2−· (EC50 0.215 and 0.132 mg/mL) in a dose-dependent manner. SP-B was also effective against lipid peroxidation in the model system. The aromatic (2Trp), acidic (2Asp and Glu), and basic (Lys) amino acid residues within the sequences of SP-B might account for its pronounced antioxidant activity. The results of this study suggested that protein hydrolysate and peptides from skate muscle might be effective as food additives for retarding lipid peroxidation occurring in foodstuffs. PMID:25854645

Two novel antioxidant nonapeptides from protein hydrolysate of skate (Raja porosa) muscle.

PubMed

Hu, Fa-Yuan; Chi, Chang-Feng; Wang, Bin; Deng, Shang-Gui

2015-04-03

In the current study, the preparation conditions of neutrase hydrolysate (SMH) from skate (Raja porosa) muscle protein were optimized using orthogonal L9(3)4 tests, and R values indicated that pH was the most important factor affecting HO· scavenging activity of SMH. Under the optimum conditions of pH 7.0, enzymolysis temperature 60 °C, enzyme/substrate ratio (E/S) 2%, and enzymolysis time 5 h, EC50 of SMH on HO· was 2.14 ± 0.17 mg/mL. Using ultrafiltration, gel filtration chromatography, and RP-HPLC, two novel antioxidant nonapeptides (SP-A and SP-B) were isolated from SMH and their amino acid sequences were found to be APPTAYAQS (SP-A) and NWDMEKIWD (SP-B) with calculated molecular masses of 904.98 Da and 1236.38 Da, respectively. Both showed strong antioxidant activities. SP-A and SP-B exhibited good scavenging activities on HO· (EC50 0.390 and 0.176 mg/mL), DPPH· (EC50 0.614 and 0.289 mg/mL), and O2-· (EC50 0.215 and 0.132 mg/mL) in a dose-dependent manner. SP-B was also effective against lipid peroxidation in the model system. The aromatic (2Trp), acidic (2Asp and Glu), and basic (Lys) amino acid residues within the sequences of SP-B might account for its pronounced antioxidant activity. The results of this study suggested that protein hydrolysate and peptides from skate muscle might be effective as food additives for retarding lipid peroxidation occurring in foodstuffs.

The SAMPL5 challenge for embedded-cluster integral equation theory: solvation free energies, aqueous p K a, and cyclohexane-water log D

NASA Astrophysics Data System (ADS)

Tielker, Nicolas; Tomazic, Daniel; Heil, Jochen; Kloss, Thomas; Ehrhart, Sebastian; Güssregen, Stefan; Schmidt, K. Friedemann; Kast, Stefan M.

2016-11-01

We predict cyclohexane-water distribution coefficients (log D 7.4) for drug-like molecules taken from the SAMPL5 blind prediction challenge by the "embedded cluster reference interaction site model" (EC-RISM) integral equation theory. This task involves the coupled problem of predicting both partition coefficients (log P) of neutral species between the solvents and aqueous acidity constants (p K a) in order to account for a change of protonation states. The first issue is addressed by calibrating an EC-RISM-based model for solvation free energies derived from the "Minnesota Solvation Database" (MNSOL) for both water and cyclohexane utilizing a correction based on the partial molar volume, yielding a root mean square error (RMSE) of 2.4 kcal mol-1 for water and 0.8-0.9 kcal mol-1 for cyclohexane depending on the parametrization. The second one is treated by employing on one hand an empirical p K a model (MoKa) and, on the other hand, an EC-RISM-derived regression of published acidity constants (RMSE of 1.5 for a single model covering acids and bases). In total, at most 8 adjustable parameters are necessary (2-3 for each solvent and two for the p K a) for training solvation and acidity models. Applying the final models to the log D 7.4 dataset corresponds to evaluating an independent test set comprising other, composite observables, yielding, for different cyclohexane parametrizations, 2.0-2.1 for the RMSE with the first and 2.2-2.8 with the combined first and second SAMPL5 data set batches. Notably, a pure log P model (assuming neutral species only) performs statistically similarly for these particular compounds. The nature of the approximations and possible perspectives for future developments are discussed.

The SAMPL5 challenge for embedded-cluster integral equation theory: solvation free energies, aqueous pK a, and cyclohexane-water log D.

PubMed

Tielker, Nicolas; Tomazic, Daniel; Heil, Jochen; Kloss, Thomas; Ehrhart, Sebastian; Güssregen, Stefan; Schmidt, K Friedemann; Kast, Stefan M

2016-11-01

We predict cyclohexane-water distribution coefficients (log D 7.4 ) for drug-like molecules taken from the SAMPL5 blind prediction challenge by the "embedded cluster reference interaction site model" (EC-RISM) integral equation theory. This task involves the coupled problem of predicting both partition coefficients (log P) of neutral species between the solvents and aqueous acidity constants (pK a ) in order to account for a change of protonation states. The first issue is addressed by calibrating an EC-RISM-based model for solvation free energies derived from the "Minnesota Solvation Database" (MNSOL) for both water and cyclohexane utilizing a correction based on the partial molar volume, yielding a root mean square error (RMSE) of 2.4 kcal mol -1 for water and 0.8-0.9 kcal mol -1 for cyclohexane depending on the parametrization. The second one is treated by employing on one hand an empirical pK a model (MoKa) and, on the other hand, an EC-RISM-derived regression of published acidity constants (RMSE of 1.5 for a single model covering acids and bases). In total, at most 8 adjustable parameters are necessary (2-3 for each solvent and two for the pK a ) for training solvation and acidity models. Applying the final models to the log D 7.4 dataset corresponds to evaluating an independent test set comprising other, composite observables, yielding, for different cyclohexane parametrizations, 2.0-2.1 for the RMSE with the first and 2.2-2.8 with the combined first and second SAMPL5 data set batches. Notably, a pure log P model (assuming neutral species only) performs statistically similarly for these particular compounds. The nature of the approximations and possible perspectives for future developments are discussed.

Phytochemical Contents and Antioxidant and Antiproliferative Activities of Selected Black and White Sesame Seeds

PubMed Central

Abbasi, Arshad Mehmood; Zheng, Bisheng

2016-01-01

Sesame (Sesamum indicum L.) seeds are popular nutritional food but with limited knowledge about their antioxidant and antiproliferative activities of various varieties. Phytochemical profiles and antioxidant and antiproliferative activities of six varieties of sesame (Sesamum indicum L.) seeds were studied. Fenheizhi3 (black) cultivar exhibited the maximum contents of total phenolics and lignans and values of total oxygen radical absorbance capacity (ORAC) and antiproliferative activity (EC50) against HepG2 cells. Bound ORAC values showed strong associations with bound phenolics contents (r = 0.976, p < 0.01); in bound phenolic extracts, EC50 values showed strong negative associations with phenolic contents (r = −0.869, p < 0.05) and ORAC values (r = −0.918, p < 0.01). Moreover, the contents of free phenolics were higher than that of the bound phenolics, and the three black sesame seeds generally depicted higher total phenolics compared to the three white varieties. The antioxidant (ORAC values) and antiproliferation activities of six sesame seeds were both associated with contents of bound phenolics (r > 0.8, p < 0.05). Interestingly, nonlignan components in bound phenolics contributed to the antioxidant and antiproliferative activities. This study suggested that Fenheizhi3 variety is superior to the other five varieties as antioxidant supplements. PMID:27597975

Short communication: Inactivation of microbial contaminants in raw milk La Serena cheese by high-pressure treatments.

PubMed

Arqués, J L; Garde, S; Gaya, P; Medina, M; Nuñez, M

2006-03-01

La Serena cheese, a Spanish variety made from Merino ewes' raw milk, has a high pH value, low salt content, and high moisture, conditions that are all favorable for growth and survival of contaminating microorganisms, including pathogens. To improve its microbiological quality and safety, high-pressure treatments at 300 or 400 MPa for 10 min at 10 degrees C were applied to 2 batches of La Serena cheese on d 2 or 50 of ripening. Cheese treated on d 2 at 300 MPa showed viable aerobic counts that were 0.99 log units lower than those for control cheese on d 3 and showed counts of enterococci, coagulase-positive staphylococci, gram-negative bacteria, and coliforms that were 2.05, 0.49, 3.14, and 4.13 log units lower, respectively, than control cheese. For cheese treated on d 2 at 400 MPa, the respective reductions in counts were 2.02, 2.68, 1.45, 3.96, and 5.50 log units. On d 60, viable aerobic counts in cheese treated on d 50 at 300 MPa were 0.50 log units lower than those in control cheese, and counts of enterococci, gram-negative bacteria, and coliforms were 1.37, 2.30, and 4.85 log units lower, respectively. For cheese treated on d 50 at 400 MPa, the respective reductions in counts were 1.29, 1.98, 4.47, and > 5 log units. High-pressure treatments at 300 or 400 MPa on d 2 or 50 reduced significantly the counts of undesirable microorganisms, improving the microbiological quality and safety of La Serena cheese immediately after treatment and at the end of the ripening period.

Biological activities of aqueous extract from Cinnamomum porrectum

NASA Astrophysics Data System (ADS)

Farah, H. Siti; Nazlina, I.; Yaacob, W. A.

2013-11-01

A study was carried out to evaluate biological activities of an extract obtained from Cinnamomum porrectum under reflux using water. Aqueous extract of Cinnamomum porrectum was tested for antibacterial activity against six Gram-positive and eight Gram-negative bacteria as well as MRSA. The results confirmed that the aqueous extract of Cinnamomum porrectum was bactericidal. Cytotoxic tests on Vero cell culture revealed that Cinnamomum porrectum was non-toxic which IC50 value higher than 0.02 mg/mL. Antiviral activity was tested based on the above IC50 values together with the measured EC50 values to obtain Therapeutic Index. The result showed that Cinnamomum porrectum has the ability to inhibit viral replication of HSV-1 in Vero cells.

Ecologic study of serum selenium and upper gastrointestinal cancers in Iran.

PubMed

Nouarie, Mehdi; Pourshams, Akram; Kamangar, Farin; Sotoudeh, Masood; Derakhshan, Mohammad Hossein; Akbari, Mohammad Reza; Fakheri, Hafez; Zahedi, Mohammad Javad; Caldwell, Kathleen; Abnet, Christian C; Taylor, Philip R; Malekzadeh, Reza; Dawsey, Sanford M

2004-09-01

Both observational and experimental studies have shown that higher selenium status reduces the risk of upper gastrointestinal cancers in selenium deficient populations. Recent cancer registry data have shown very different rates of esophageal cancer (EC) and gastric cancer (GC) in four Provinces of Iran, namely Ardabil, Mazandaran, Golestan, and Kerman. The aim of this study was to have a preliminary assessment of the hypothesis that high rates of EC in Golestan and high rates of GC in Ardabil may be partly attributable to selenium deficiency. We measured serum selenium in 300 healthy adults from Ardabil (n = 100), Mazandaran (n = 50), Golestan (n = 100), and Kerman (n = 50), using inductively coupled plasma, with dynamic reaction cell, mass spectrometry (ICP-DRC-MS) at the US Centers for Disease Control (Atlanta, Georgia). The median serum selenium concentrations were very different in the four Provinces. The medians (IQR) for selenium in Ardabil, Mazandarn, Golestan, and Kerman were 82 (75-94), 123 (111-132), 155 (141-173), and 119 (110-128) microg/L, respectively (P<0.001). The results of linear regression showed that the Province variable, by itself, explained 76% of the variance in log selenium (r2 = 0.76). The proportion of the populations with a serum selenium more than 90 microg/L (the concentration at which serum selenoproteins are saturated) was 100% in Golestan, Kerman, and Mazandaran but only 29% in Ardabil. Our findings suggest that selenium deficiency is not a major contributor to the high incidence of EC seen in northeastern Iran, but it may play a role in the high incidence of GC in Ardabil Province. Copyright 2004 The WJG Press ISSN

Cardiovascular effects of fentanyl in conscious rats.

PubMed

Baechtold, F; Cavadas, C; Gasser, D; Markert, M; Grouzmann, E; Peterson, K L; Waeber, B; Feihl, F

2001-10-01

The polymicrobial sepsis induced by cecal ligation and puncture (CLP) in the rat is widely used in shock research. For ethical reasons, narcotic analgesics are often administered in this model, with the potential risk of confounding effects. In conscious non-septic rats, we investigated the cardiovascular effects of a continuous i.v. infusion of fentanyl (20 microg/kg per h) administered with fluid loading (10 ml/kg per h) for 24 h, a regimen commonly applied in rat CLP. Animals were randomly allocated to receive analgesia with fluid loading (Fentanyl group), or fluid loading alone (Control). All endpoints were assessed after 24 h of infusion. At that time, Control animals had mild respiratory alkalosis, which was essentially abolished by fentanyl. Analgesia mildly elevated the plasma norepinephrine levels [median (interquartile range): Control 232 pg/ml (0-292), Fentanyl 302 pg/ml (234-676), P=0.045] but was devoid of any effect on blood pressure, heart rate, cardiac output (mean +/-SD: Control 388+/-61 ml/kg per min, Fentanyl 382+/-62 ml/kg per min, P=0.87) and indices of left ventricular function derived from high-fidelity recordings of left ventricular pressure (dP/dtmax: Control 11782+/-2324 mmHg/s, Fentanyl 12107+/-2816 mmHg/s, P=0.77). In ex vivo experiments carried out immediately after animal sacrifice, no differences were noted between the Control and Fentanyl groups in the sensitivity of endothelium-intact aortic rings to norepinephrine-induced vasoconstriction (-logEC50: Control 8.78+/-0.28, Fentanyl 8.83+/-0.26, P=0.52) or acetylcholine-induced vasodilatation (-logEC50: Control 7.00+/-0.37, Fentanyl 7.06+/-0.26+/-0.53, P=0.75). In conclusion, the present data provide no contraindication, and even some support for the ethical use of a high dose i.v. infusion of fentanyl in cardiovascular studies of conscious catheterized rats undergoing CLP or other painful procedures.

Attenuation of cardiac fibrosis by pirfenidone and amiloride in DOCA-salt hypertensive rats

PubMed Central

Mirkovic, Stevo; Seymour, Anne-Marie L; Fenning, Andrew; Strachan, Anna; Margolin, Solomon B; Taylor, Stephen M; Brown, Lindsay

2002-01-01

This study has administered pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone) or amiloride to attenuate the remodelling and associated functional changes, especially an increased cardiac stiffness, in DOCA-salt hypertensive rats. In control rats, the elimination half-life of pirfenidone following a single intravenous dose of 200 mg kg−1 was 37 min while oral bioavailability at this dose was 25.7%. Plasma pirfenidone concentrations in control rats averaged 1.9±0.1 μg ml−1 over 24 h after 14 days' administration as a 0.4% mixture in food. Pirfenidone (approximately 250 – 300 mg kg−1 day−1 as 0.4% in food) and amiloride (1 mg kg−1 day−1 sc) were administered for 2 weeks starting 2 weeks post-surgery. Pirfenidone but not amiloride attenuated ventricular hypertrophy (2.69±0.09, UNX 2.01±0.05. DOCA-salt 3.11±0.09 mg kg−1 body wt) without lowering systolic blood pressure. Collagen deposition was significantly increased in the interstitium after 2 weeks and further increased with scarring of the left ventricle after 4 weeks; pirfenidone and amiloride reversed the increases and prevented further increases. This accumulation of collagen was accompanied by an increase in diastolic stiffness constant; both amiloride and pirfenidone reversed this increase. Noradrenaline potency (positive chronotropy) was decreased in right atria (neg log EC50: control 6.92±0.06; DOCA-salt 6.64±0.08); pirfenidone but not amiloride reversed this change. Noradrenaline was a more potent vasoconstrictor in thoracic aortic rings (neg log EC50: control 6.91±0.10; DOCA-salt 7.90±0.07); pirfenidone treatment did not change noradrenaline potency. Thus, pirfenidone and amiloride reverse and prevent cardiac remodelling and the increased cardiac stiffness without reversing the increased vascular responses to noradrenaline. PMID:11861324

Mixture toxicity of the anti-inflammatory drugs diclofenac, ibuprofen, naproxen, and acetylsalicylic acid.

PubMed

Cleuvers, Michael

2004-11-01

The ecotoxicity of the nonsteroidal anti-inflammatory drugs (NSAIDs) diclofenac, ibuprofen, naproxen, and acetylsalicylic acid (ASA) has been evaluated using acute Daphnia and algal tests. Toxicities were relatively low, with half-maximal effective concentration (EC50) values obtained using Daphnia in the range from 68 to 166 mg L(-1) and from 72 to 626 mg L(-1) in the algal test. Acute effects of these substances seem to be quite improbable. The quantitative structure-activity relationships (QSAR) approach showed that all substances act by nonpolar narcosis; thus, the higher the n-octanol/water partitioning coefficient (log Kow) of the substances, the higher is their toxicity. Mixture toxicity of the compounds could be accurately predicted using the concept of concentration addition. Toxicity of the mixture was considerable, even at concentrations at which the single substances showed no or only very slight effects, with some deviations in the Daphnia test, which could be explained by incompatibility of the very steep dose-response curves and the probit analysis of the data. Because pharmaceuticals in the aquatic environment occur usually as mixtures, an accurate prediction of the mixture toxicity is indispensable for environmental risk assessment.

Comparison of protocols measuring diffusion and partition coefficients in the stratum corneum

PubMed Central

Rothe, H.; Obringer, C.; Manwaring, J.; Avci, C.; Wargniez, W.; Eilstein, J.; Hewitt, N.; Cubberley, R.; Duplan, H.; Lange, D.; Jacques‐Jamin, C.; Klaric, M.; Schepky, A.

2017-01-01

Abstract Partition (K) and diffusion (D) coefficients are important to measure for the modelling of skin penetration of chemicals through the stratum corneum (SC). We compared the feasibility of three protocols for the testing of 50 chemicals in our main studies, using three cosmetics‐relevant model chemicals with a wide range of logP values. Protocol 1: SC concentration‐depth profile using tape‐stripping (measures KSC/v and DSC/HSC 2, where HSC is the SC thickness); Protocol 2A: incubation of isolated SC with chemical (direct measurement of KSC/v only) and Protocol 2B: diffusion through isolated SC mounted on a Franz cell (measures KSC/v and DSC/HSC 2, and is based on Fick's laws). KSC/v values for caffeine and resorcinol using Protocol 1 and 2B were within 30% of each other, values using Protocol 2A were ~two‐fold higher, and all values were within 10‐fold of each other. Only indirect determination of KSC/v by Protocol 2B was different from the direct measurement of KSC/v by Protocol 2A and Protocol 1 for 7‐EC. The variability of KSC/v for all three chemicals using Protocol 2B was higher compared to Protocol 1 and 2A. DSC/HSC 2 values for the three chemicals were of the same order of magnitude using all three protocols. Additionally, using Protocol 1, there was very little difference between parameters measured in pig and human SC. In conclusion, KSC/v, and DSC values were comparable using different methods. Pig skin might be a good surrogate for human skin for the three chemicals tested. Copyright © 2017 The Authors Journal of Applied Toxicology published by John Wiley & Sons Ltd. PMID:28139006

Effects of some benzoxazinoids on in vitro growth of Cephalosporium gramineum and other fungi pathogenic to cereals and on Cephalosporium stripe of winter wheat.

PubMed

Martyniuk, Stefan; Stochmal, Anna; Macías, Francisco A; Marín, David; Oleszek, Wieslaw

2006-02-22

The benzoxazolinones benzoxazolin-2(3H)-one (BOA) and 6-methoxybenzoxazolin-2(3H)-one (MBOA) and selected degradation products of these compounds were examined for their in vitro antifungal activity against Cephalosporium gramineum, Gaeumannomyces graminis var. graminis, and Fusarium culmorum. BOA was also applied to the soil-incorporated inoculum of C. gramineum to test its capability of reducing Cephalosporium stripe disease in winter wheat. MBOA reduced the mycelial growth of G. graminis var. tritici, C. gramineum, and F. culmorum by 50% (EC50) at the concentrations of 77, 134, and 271 microg/mL of corn meal agar, respectively, and the corresponding BOA EC50 values for the fungi were 11, 189, and 456 microg/mL. BOA degradation products 2-amino-3H-phenoxazin-3-one (APO), 2-acetylamino-3H-phenoxazin-3-one (AAPO), and o-aminophenol (o-AP) were much more inhibitory to the growth of C. gramineum and G. graminis var. tritici than the parent compounds. APO, AAPO, and o-AP EC50 values were found to be as low as 0.58, 4.57, and 1.4 microg/mL, respectively, for C. gramineum and 0.78, 2.18, and 0.80 microg/mL for G. graminis var. tritici. These compounds applied at the corresponding concentrations did not significantly affect the mycelial growth of F. culmorum. The treatment of C. gramineum inoculum with a 1% water solution of BOA resulted in a significant reduction infection of winter wheat with C. gramineum as compared to the control with the untreated inoculum,but this treatment was not as effective as the application of a commercial fungicide.

Evaluation of ecotoxicological effects of benzophenone UV filters: Luminescent bacteria toxicity, genotoxicity and hormonal activity.

PubMed

Zhang, Qiuya; Ma, Xiaoyan; Dzakpasu, Mawuli; Wang, Xiaochang C

2017-08-01

The widespread use of organic ultraviolet (UV) filters in personal care products raises concerns about their potentially hazardous effects on human and ecosystem health. In this study, the toxicities of four commonly used benzophenones (BPs) UV filters including benzophenone (BP), 2-Hydroxybenzophenone (2HB), 2-Hydroxy-4-methoxybenzophenone (BP3), and 2-Hydroxy-4-methoxybenzophenone-5-sulfonicacid (BP4) in water were assayed in vitro using Vibrio fischeri, SOS/umu assay, and yeast estrogen screen (YES) assay, as well as in vivo using zebrafish larvae. The results showed that the luminescent bacteria toxicity, expressed as logEC 50 , increased with the lipophilicity (logKow) of BPs UV filters. Especially, since 2HB, BP3 and BP4 had different substituent groups, namely -OH, -OCH 3 and -SO 3 H, respectively, these substituent functional groups had a major contribution to the lipophilicity and acute toxicity of these BPs. Similar tendency was observed for the genotoxicity, expressed as the value of induction ratio=1.5. Moreover, all the target BPs UV filters showed estrogenic activity, but no significant influences of lipophilicity on the estrogenicity were observed, with BP3 having the weakest estrogenic efficiency in vitro. Although BP3 displayed no noticeable adverse effects in any in vitro assays, multiple hormonal activities were observed in zebrafish larvae including estrogenicity, anti-estrogenicity and anti-androgenicity by regulating the expression of target genes. The results indicated potential hazardous effects of BPs UV filters and the importance of the combination of toxicological evaluation methods including in vitro and in vivo assays. Copyright © 2017 Elsevier Inc. All rights reserved.

Ecotoxicological potential of the biocides terbutryn, octhilinone and methylisothiazolinone: Underestimated risk from biocidal pathways?

PubMed

Kresmann, Simon; Arokia, Arokia Hansel Rajan; Koch, Christoph; Sures, Bernd

2018-06-01

The use of biocides by industry, agriculture and households increased throughout the last two decades. Many new applications with known substances enriched the variety of biocidal pollution sources for the aquatic environment. While agriculture was the major source for a long time, leaching from building facades and preservation of personal care and cleaning products was identified as new sources in the last few years. With the different usage forms of biocidal products the complexity of legislative regulation increased as well. The requirements for risk assessment differ from one law to another and the potential risk of substances under different regulations might be underestimated. Still EC 50 and predicted no-effect concentration (PNEC) values gained from testing with different species are the core of environmental risk assessment, but ecotoxicological data is limited or lacking for many biocides. In this study the biocides widely used in facade coatings and household products terbutryn, octhilinone and methylisothiazolinone were tested with the Daphnia magna acute immobilisation assay, the neutral red uptake assay and the ethoxyresorufin-O-deethylase (EROD) assay, performed with rainbow trout liver (RTL-W1) cells. Further, the MTT assay with the ovarian cell line CHO-9 from Chinese hamster was used as mammalian model. Octhilinone induced the strongest effects with EC 50 values of 156μg/l in the D. magna assay, while terbutryn showed the weakest effects with 8390μg/l and methylisothiazolinone 513μg/l respectively. All other assays showed higher EC 50 values and thus only weak effects. EROD assays did not show any effects. With additional literature and database records PNEC values were calculated: terbutryn reached 0.003μg/l, octhilinone 0.05μg/l and methylisothiazolinone 0.5μg/l. Potential ecotoxicological risks of these biocides are discussed, considering environmental concentrations. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of coniine on presynaptic nicotinic receptors.

PubMed

Erkent, Ulkem; Iskit, Alper B; Onur, Rustu; Ilhan, Mustafa

2016-01-01

Toxicity of coniine, an alkaloid of Conium maculatum (poison hemlock), is manifested by characteristic nicotinic clinical signs including excitement, depression, hypermetria, seizures, opisthotonos via postsynaptic nicotinic receptors. There is limited knowledge about the role of presynaptic nicotinic receptors on the pharmacological and toxicological effects of coniine in the literature. The present study was undertaken to evaluate the possible role of presynaptic nicotinic receptors on the pharmacological and toxicological effects of coniine. For this purpose, the rat anococcygeus muscle and guinea-pig atria were used in vitro. Nicotine (100 μM) elicited a biphasic response composed of a relaxation followed by contraction through the activation of nitrergic and noradrenergic nerve terminals in the phenylephrine-contracted rat anococcygeus muscle. Coniine inhibited both the nitrergic and noradrenergic response in the muscle (-logIC(50) = 3.79 ± 0.11 and -logIC(50) = 4.57 ± 0.12 M, respectively). The effect of coniine on nicotinic receptor-mediated noradrenergic transmission was also evaluated in the guinea-pig atrium (-logIC(50) = 4.47 ± 0.12 M) and did not differ from the -logIC(50) value obtained in the rat anococcygeus muscle. This study demonstrated that coniine exerts inhibitory effects on nicotinic receptor-mediated nitrergic and noradrenergic transmitter response.

Calibration of a modified temperature-light intensity logger for quantifying water electrical conductivity

NASA Astrophysics Data System (ADS)

Gillman, M. A.; Lamoureux, S. F.; Lafrenière, M. J.

2017-09-01

The Stream Temperature, Intermittency, and Conductivity (STIC) electrical conductivity (EC) logger as presented by Chapin et al. (2014) serves as an inexpensive (˜50 USD) means to assess relative EC in freshwater environments. This communication demonstrates the calibration of the STIC logger for quantifying EC, and provides examples from a month long field deployment in the High Arctic. Calibration models followed multiple nonlinear regression and produced calibration curves with high coefficient of determination values (R2 = 0.995 - 0.998; n = 5). Percent error of mean predicted specific conductance at 25°C (SpC) to known SpC ranged in magnitude from -0.6% to 13% (mean = -1.4%), and mean absolute percent error (MAPE) ranged from 2.1% to 13% (mean = 5.3%). Across all tested loggers we found good accuracy and precision, with both error metrics increasing with increasing SpC values. During 10, month-long field deployments, there were no logger failures and full data recovery was achieved. Point SpC measurements at the location of STIC loggers recorded via a more expensive commercial electrical conductivity logger followed similar trends to STIC SpC records, with 1:1.05 and 1:1.08 relationships between the STIC and commercial logger SpC values. These results demonstrate that STIC loggers calibrated to quantify EC are an economical means to increase the spatiotemporal resolution of water quality investigations.

German Adjuvant Intergroup Node-positive Study (GAIN): a phase III trial comparing two dose-dense regimens (iddEPC versus ddEC-PwX) in high-risk early breast cancer patients.

PubMed

Möbus, V; von Minckwitz, G; Jackisch, C; Lück, H-J; Schneeweiss, A; Tesch, H; Elling, D; Harbeck, N; Conrad, B; Fehm, T; Huober, J; Müller, V; Bauerfeind, I; du Bois, A; Loibl, S; Nekljudova, V; Untch, M; Thomssen, C

2017-08-01

Dose-dense (dd) regimens are one of the preferred options for the adjuvant treatment of breast cancer patients with intermediate to high risk. The German Adjuvant Intergroup Node-positive trial aimed at optimizing intense dd (idd) strategies by evaluating drug combinations and the addition of capecitabine. Women (aged 18 years and biologically <65 years) with histologically involved axillary lymph nodes were randomly assigned to receive three courses each of epirubicin (E) 150 mg/m2, paclitaxel (P) 225 mg/m2 and cyclophosphamide (C) 2500 mg/m2 (reduced to 2000 mg/m2 after recruitment of 1200 patients) q2w intravenously (i.v.) (iddEPC-regimen) or ddEC (E 112.5 mg/m2 + C 600 mg/m2, i.v. q2w for 4 cycles) followed by paclitaxel weekly (Pw 67.5 mg/m2 i.v. q8d for 10 weeks) plus capecitabine (X 2000 mg/m2 p.o. days 1-14, q22 for 4 cycles) (ddEC-PwX-regimen). Further randomization assigned patients to ibandronate for 2 years versus observation and to pegfilgrastim day 2 versus 4. From June 2004 to August 2008, 2994 patients were randomized to either iddEPC (N = 1498), or ddEC-PwX (N = 1496) and started treatment. Median age was 50 years; pN1 (37.8%), pN2 (35.3%); pN3 (26.9%); 46.4% were G3 tumors; 76.9% hormone receptor-positive and 22% HER2-positive. After a median follow-up of 74 months, 645 events and 383 deaths were recorded. Hematological adverse events grades 3-4 were more common with iddEPC (P < 0.001), nonhematological with ddEC-PwX (P = 0.04), even if the toxicity profile of the two regimens was different. At 5 years, estimated disease-free survival rates for ddEC-PwX and iddEPC were 81.7% [95% confidence interval (CI) 79.5-83.6] versus 80.2% (95% CI 78.0-82.2). Hazard ratio (HR)=0.95 (95% CI 0.81-1.11, log-rank P = 0.49). Five-year overall survival rates were 89.4% for ddEC-PwX (95% CI 87.7-91.0) and 89.0% for iddEPC (95% CI 87.2-90.6), HR = 0.85 (95% CI 0.69-1.04, log-rank P = 0.10). Adding capecitabine to ddEC-Pw did not improve outcome in comparison to iddEPC but increased toxicity and should not be recommended for further use. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Contribution for the Derivation of a Soil Screening Value (SSV) for Uranium, Using a Natural Reference Soil

PubMed Central

Caetano, Ana Luisa; Marques, Catarina R.; Gavina, Ana; Carvalho, Fernando; Gonçalves, Fernando; da Silva, Eduardo Ferreira; Pereira, Ruth

2014-01-01

In order to regulate the management of contaminated land, many countries have been deriving soil screening values (SSV). However, the ecotoxicological data available for uranium is still insufficient and incapable to generate SSVs for European soils. In this sense, and so as to make up for this shortcoming, a battery of ecotoxicological assays focusing on soil functions and organisms, and a wide range of endpoints was carried out, using a natural soil artificially spiked with uranium. In terrestrial ecotoxicology, it is widely recognized that soils have different properties that can influence the bioavailability and the toxicity of chemicals. In this context, SSVs derived for artificial soils or for other types of natural soils, may lead to unfeasible environmental risk assessment. Hence, the use of natural regional representative soils is of great importance in the derivation of SSVs. A Portuguese natural reference soil PTRS1, from a granitic region, was thereby applied as test substrate. This study allowed the determination of NOEC, LOEC, EC20 and EC50 values for uranium. Dehydrogenase and urease enzymes displayed the lowest values (34.9 and <134.5 mg U Kg, respectively). Eisenia andrei and Enchytraeus crypticus revealed to be more sensitive to uranium than Folsomia candida. EC50 values of 631.00, 518.65 and 851.64 mg U Kg were recorded for the three species, respectively. Concerning plants, only Lactuca sativa was affected by U at concentrations up to 1000 mg U kg1. The outcomes of the study may in part be constrained by physical and chemical characteristics of soils, hence contributing to the discrepancy between the toxicity data generated in this study and that available in the literature. Following the assessment factor method, a predicted no effect concentration (PNEC) value of 15.5 mg kg−1 dw was obtained for U. This PNEC value is proposed as a SSV for soils similar to the PTRS1. PMID:25353962

Optimal effect-site concentration of remifentanil when combined with dexmedetomidine in patients undergoing cystoscopy

PubMed Central

Heo, Bongha; Kim, Minsun; Lee, Hyunjung; Park, Sanghee

2014-01-01

Background Cystoscopic procedure is a very common practice in the field of urology due to its ability to survey the bladder for a variety of indications. However, patients who undergo cystoscopy feel intense pain and discomfort. This study investigated the half maximal effective concentration (EC50) of remifentanil in preventing cystoscope insertion pain under sedation using dexmedetomidine. Methods The study was prospectively conducted on 18 male patients, aged 18 to 65. Remifentail infusion was initiated together with dexmedetomidine, and started at a dose of 2.4 ng/ml on the first patient. The effect-site concentration (Ce) of remifentanil for each subsequent patient was determined by the previous patient's response using Dixon's up-and-down method with an interval of 0.3 ng/ml. Patients received a loading dose of 1.0 µg/kg dexmedetomidine over 10 minutes, followed by a maintenance dose of 0.6 µg/kg/hr. After the patient's OAA/S score (Observer's Assessment of Alertness/Sedation scale) reached 3-4, and the Ce of remifentanil reached target concentration, the urologist was allowed to insert the cystoscope and the pain responses were observed. Results The effect-site concentration of remifentanil required to prevent cystoscope insertion pain in 50% of patients under sedation using dexmedetomidine was 1.30 ± 0.12 ng/ml by Dixon's up-and-down method. The logistic regression curve of the probability of response showed that the EC50 and EC95 values (95% confidence limits) of remifentanil were 1.33 ng/ml (1.12-1.52 ng/ml) and 1.58 ng/ml (1.44-2.48 ng/ml), respectively. Conclusions Cystoscopic procedure can be carried out successfully without any pain or adverse effects by optimal remifentanil effect-site concentration (EC50, 1.33 ng/ml; EC95, 1.58 ng/ ml) combined with sedation using dexmedetomidine. PMID:24567812

A role for the anandamide membrane transporter in TRPV1-mediated neurosecretion from trigeminal sensory neurons

PubMed Central

Price, Theodore J.; Patwardhan, Amol M.; Flores, Christopher M.; Hargreaves, Kenneth M.

2007-01-01

Many n-acylethanolamines utilize the anandamide membrane transporter (AMT) to gain facilitated access to the intracellular compartment, hence, we hypothesized that this mechanism might be important for anandamide (AEA)- and N-arachidonoyl-dopamine (NADA)-evoked CGRP release from cultured trigeminal ganglion (TG) neurons. Using [14C]AEA we demonstrated that TG neurons transported AEA in a FAAH- and AMT-inhibitable fashion. Although TRPV1-positive TG neurons were found to express fatty acid amide hydrolase, the application of FAAH inhibitors had no effect on AEA-evoked CGRP release. In contrast, application of the AMT inhibitors OMDM-2 or VDM-11 significantly reduced the potency and efficacy of AEA-, NADA- and capsaicin-evoked CGRP release. Moreover OMDM-2 (IC50 values ranging from 6.4–9.6 μM) and VDM-11 (IC50 values ranging from 5.3–11 μM) inhibited CGRP release evoked by EC80 concentrations of AEA, NADA and CAP and these values were consistent with IC50s obtained for inhibition of uptake. OMDM-2 had no effect on CGRP release per se while VDM-11 evoked CGRP release on its own (EC50 ~35 μM) in a CPZ-insensitive, but ruthenium red (RR)-sensitive fashion. This is the first demonstration that TG sensory neurons possess an AMT-like mechanism suggesting that this mechanism is important for the pharmacological action of AEA and NADA at native TRPV1 channels. PMID:15992578

Microbial risk assessment with the OAEL approach at water abstraction points in rural Kenya

NASA Astrophysics Data System (ADS)

Yillia, Paul T.; Kreuzinger, Norbert; Mathooko, Jude M.; Ndomahina, Ernest T.

US-based models for recreational water quality were applied to characterize the potential health risk (PHR) of infection with gastroenteritis (GI) and highly credible gastroenteritis (HCGI) illnesses from single exposure at several water abstraction points (WAPs) along the Njoro River in rural Kenya. Ambient geometric mean densities of Escherichia coli (EC) and intestinal enterococci (IE) were generally high (2-4 log units of cfu/100 ml) and risk levels were grossly in excess of acceptable health risk (AHR) levels for bathing and drinking. PHR was 2-3 times higher with the Cabelli (IE) model (Equation (2)) compared to the US EPA (EC) model (Equation (1)). Risk levels varied among WAPs in concomitance to the spatial and seasonal variability of ambient EC and IE densities. With the Cabelli IE model, PHR of HCGI illness on single exposure to the dry weather 95th percentile IE density for bathing was 2.5% of the exposed population at Logoman compared to 5.2% at Turkana Flats, 4.9% at Kenyatta or Nessuit and 4.6%, 4.5% and 4.2% at Treetop, Segotik and Njoro Bridge, respectively. PHR was ⩾5% on exposure to the wet weather 95th percentile IE density at all WAPs, excepting Treetop with 4.3%. Relative risk levels increased by at least 30 and 70 times for GI and HCGI illnesses, respectively, from drinking (250 ml) raw stream water, rising erratically in wet weather by >80% of the dry weather risk at Logoman, >30% at Njoro Bridge and Kenyatta and 10-15% at Segotik, Nessuit and Turkana Flats. By stipulating freshwater bathing water quality guidelines of 126 and 33 cfu/100 ml for EC and IE, respectively, US, EPA upholds maximum AHR levels at 0.7% and 1.9% for EC and IE, respectively. Hence, reducing current PHR levels at the WAPs to the US, EPA bathing AHR levels would require at least 2-4 log reductions of IE and EC densities with even further log reductions to achieve the WHO recommended drinking water AHR level of 0.1%. This would necessitate specialized treatment, in particular point-of-use treatment at the household level, as well as the implementation of comprehensive catchment management measures to protect the stream and the WAPs.

Retrieval of atmospheric elemental carbon records using lake sediments: Implications in radiative forcing

NASA Astrophysics Data System (ADS)

Ahmed, Tanveer

Elemental or black carbon (EC or BC) aerosols produced during incomplete combustion strongly absorb solar radiation and contribute to global warming, and cause cardiopulmonary disease. Long-term atmospheric EC measurements, [EC]atm, are needed to validate global climate models to estimate the impact of EC on earth's temperature. Such data is sparse. In this work, a new technique was developed to retrieve the historical record of [EC]atm in the Northeastern US for the past two centuries. Measurements of [EC]atm were made in the monthly composites of daily filters collected over ˜30 yr at Whiteface Mountain (WFM), NY using the thermal optical method. Bottom sediment cores were collected from four lakes near WFM. They were sliced in horizontal sections, freeze dried, and their ages determined 210Pb dating technique. EC in sediments was chemically separated and its concentration determined using the same thermal-optical method. It was shown that [EC]sed = K [EC]atm where K is constant (m3/g). Measurements of [EC]atm and [EC]sed for the ˜1978 to 2005 period was used to determine the value for K. The value of K and [EC]sed for periods before 1978 were used to determine [EC]atm for the past ˜100 yrs. [EC]atm in the preindustrial period in US, ˜1850, varied between 38 and 73 ng/m3, with a mean value of 56 +/- 14 ng/m3. [EC]atm was found to increase sharply with rapid industrialization and reached its maximum value of 751 +/- 265 ng/m3 during 1920s, which was a factor of ˜12 higher compared to the mean preindustrial level. The [EC]atm declined gradually until ˜1980 and then decreased sharply. Directly measured values of [EC]atm are only ˜25% higher compared to the mean preindustrial level. Model US EC emissions estimates of Novakov et al. (2003), based on energy consumptions, reproduce our [EC]sed trends quite well for the ˜1900 to 1930 period. Subsequently, the model EC values drop-off more rapidly than our [EC]atm. To extend the technique where long tern [EC]atm are not available, a new generalized mathematical model expression to determine K was developed. The value of K calculated using the model agreed within +/-30% with the measurements.

α2-Adrenoceptor Functionality in Postmortem Frontal Cortex of Depressed Suicide Victims

PubMed Central

Valdizán, Elsa M.; Díez-Alarcia, Rebeca; González-Maeso, Javier; Pilar-Cuéllar, Fuencisla; García-Sevilla, Jesús A.; Meana, J. Javier; Pazos, Angel

2013-01-01

Background Alterations in brain density and signaling associated with monoamine receptors are believed to play a role in depressive disorders. This study evaluates the functional status of α2A-adrenoceptors in postmortem frontal cortex of depressed subjects. Methods G-protein activation and inhibition of adenylyl cyclase (AC) activity induced by the α2-adrenoceptor agonist UK14304 were measured in triplicate in samples from 15 suicide victims with an antemortem diagnosis of major depression and 15 matched control subjects. Results Basal [35S] guanosine γ thio-phosphate (GTPγS) binding and cyclic adenosine monophosphate accumulation did not differ between groups. In depressed victims, an increase in [35S] GTPγS binding potency (EC50 = .58 μmol/L vs. EC50 = 3.31 μmol/L; p < .01; depressed vs. control) and a significant reduction in the maximal inhibition of AC activity (Imax = 27 ± 4% vs. Imax = 47 ± 5%; p < .01) were observed after incubation with the α2-adrenoceptor agonist UK14304. No differences were found between antidepressant-free and antidepressant-treated subjects. A significant relationship between EC50 values for [35S] GTPγS and Imax values for AC assay was found (n = 30; r = −.43; p < .05). Conclusions The dual regulation of α2A-adrenoceptor signaling pathways raises the possibility that factors affecting the G-protein cycle and/or selective access of Gαi/o–protein to AC might be relevant to receptor abnormalities in depression, providing further support for the involvement of α2A-adrenoceptors in the pathogenesis of depression. PMID:20864091

Design, Synthesis, and Antifouling Activity of Glucosamine-Based Isocyanides

PubMed Central

Hasegawa, Yuki; Novita, Ira S.; Suzuki, Junya; Morozumi, Tatsuya; Nogata, Yasuyuki; Yoshimura, Erina; Matsuda, Fuyuhiko

2017-01-01

Biofouling, an undesirable accumulation of organisms on sea-immersed structures such as ship hulls and fishing nets, is a serious economic issue whose effects include oil wastage and clogged nets. Organotin compounds were utilized since the 1960s as an antifouling material; however, the use of such compounds was later banned by the International Maritime Organization (IMO) due to their high toxicity toward marine organisms, resulting in masculinization and imposex. Since the ban, there have been extensive efforts to develop environmentally benign antifoulants. Natural antifouling products obtained from marine creatures have been the subject of considerable attention due to their potent antifouling activity and low toxicity. These antifouling compounds often contain isocyano groups, which are well known to have natural antifouling properties. On the basis of our previous total synthesis of natural isocyanoterpenoids, we envisaged the installation of an isocyano functional group onto glucosamine to produce an environmentally friendly antifouling material. This paper describes an effective synthetic method for various glucosamine-based isocyanides and evaluation of their antifouling activity and toxicity against cypris larvae of the barnacle Amphibalanus amphitrite. Glucosamine isocyanides with an ether functionality at the anomeric position exhibited potent antifouling activity, with EC50 values below 1 μg/mL, without detectable toxicity even at a high concentration of 10 μg/mL. Two isocyanides had EC50 values of 0.23 and 0.25 μg/mL, comparable to that of CuSO4, which is used as a fouling inhibitor (EC50 = 0.27 μg/mL). PMID:28661419

Sensitivity of Scenedesmus obliquus and Microcystis aeruginosa to atrazine: effects of acclimation and mixed cultures, and their removal ability.

PubMed

Chalifour, Annie; LeBlanc, André; Sleno, Lekha; Juneau, Philippe

2016-12-01

Atrazine is an herbicide frequently detected in watercourses that can affect the phytoplankton community, thus impacting the whole food chain. This study aims, firstly, to measure the sensitivity of monocultures of the green alga Scenedemus obliquus and toxic and non-toxic strains of the cyanobacteria Microcystis aeruginosa before, during and after a 30-day acclimation period to 0.1 µM of atrazine. Secondly, the sensitivity of S. obliquus and M. aeruginosa to atrazine in mixed cultures was evaluated. Finally, the ability of these strains to remove atrazine from the media was measured. We demonstrated that both strains of M. aeruginosa had higher growth rate-based EC 50 values than S. obliquus when exposed to atrazine, even though their photosynthesis-based EC 50 values were lower. After being exposed to 0.1 µM of atrazine for 1 month, only the photosynthesis-based EC 50 of S. obliquus increased significantly. In mixed cultures, the growth rate of the non-toxic strain of M. aeruginosa was higher than S. obliquus at high concentrations of atrazine, resulting in a ratio of M. aeruginosa to total cell count of 0.6. This lower sensitivity might be related to the higher growth rate of cyanobacteria at low light intensity. Finally, a negligible fraction of atrazine was removed from the culture media by S. obliquus or M. aeruginosa over 6 days. These results bring new insights on the acclimation of some phytoplankton species to atrazine and its effect on the competition between S. obliquus and M. aeruginosa in mixed cultures.

Fused heterocycles bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 2: discovery of novel [1,2,4]Triazolo[1,5-a]pyrimidines using a structure-guided core-refining approach.

PubMed

Wang, Liu; Tian, Ye; Chen, Wenmin; Liu, Hong; Zhan, Peng; Li, Dongyue; Liu, Huiqing; De Clercq, Erik; Pannecouque, Christophe; Liu, Xinyong

2014-10-06

Guided by crystal structures of HIV-1 RT/DAPY complex and molecular modeling studies, a series of novel [1,2,4]triazolo[1,5-a]pyrimidine derivatives were rationally designed via structure-based core refining approach, synthesized through the readily accessible synthetic methods and evaluated for their anti-HIV activities in MT-4 cells. Preliminary biological evaluation indicated that most of the compounds exhibited marked inhibitory activity against the wild-type HIV-1 IIIB. Particularly, compound 7n was the most potent inhibitor against wild-type and K103N/Y181C double resistant mutant strain of HIV-1, possessing EC50 values of 0.02 μM and 7.6 μM, respectively, which were much better than or similar to nevirapine (NVP, EC50 = 0.15 μM, 2.9 μM) and delavirdine (DLV, EC50 = 0.07 μM, >36 μM). Besides, some other compounds, 5b, 7c, 7e, 7f, and 7m, were also endowed with favorable anti-HIV-1 potency (EC50 = 0.07, 0.05, 0.05, 0.07, and 0.05 μM, respectively), which were better than or similar to those of NVP and DLV, suggesting a high potential to further develop this type of bridgehead nitrogen heterocycle as a novel class of NNRTIs with improved antiviral efficacy and resistance profile. The selected compound, 7i, was found moderately inhibitory towards RT (IC50 = 0.39 μM), which was higher than for ETV (IC50 = 0.56 μM). Preliminary structure-activity relationships (SARs) and molecular modeling of these new analogues were detailed in this manuscript. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

In Vitro Antiviral Activity and Resistance Profile of the Next-Generation Hepatitis C Virus NS5A Inhibitor Pibrentasvir.

PubMed

Ng, Teresa I; Krishnan, Preethi; Pilot-Matias, Tami; Kati, Warren; Schnell, Gretja; Beyer, Jill; Reisch, Thomas; Lu, Liangjun; Dekhtyar, Tatyana; Irvin, Michelle; Tripathi, Rakesh; Maring, Clarence; Randolph, John T; Wagner, Rolf; Collins, Christine

2017-05-01

Pibrentasvir (ABT-530) is a novel and pan-genotypic hepatitis C virus (HCV) NS5A inhibitor with 50% effective concentration (EC 50 ) values ranging from 1.4 to 5.0 pM against HCV replicons containing NS5A from genotypes 1 to 6. Pibrentasvir demonstrated similar activity against a panel of chimeric replicons containing HCV NS5A of genotypes 1 to 6 from clinical samples. Resistance selection studies were conducted using HCV replicon cells with NS5A from genotype 1a, 1b, 2a, 2b, 3a, 4a, 5a, or 6a at a concentration of pibrentasvir that was 10- or 100-fold over its EC 50 for the respective replicon. With pibrentasvir at 10-fold over the respective EC 50 , only a small number of colonies (0.00015 to 0.0065% of input cells) with resistance-associated amino acid substitutions were selected in replicons containing genotype 1a, 2a, or 3a NS5A, and no viable colonies were selected in replicons containing NS5A from other genotypes. With pibrentasvir at 100-fold over the respective EC 50 , very few colonies (0.0002% of input cells) were selected by pibrentasvir in genotype 1a replicon cells while no colonies were selected in other replicons. Pibrentasvir is active against common resistance-conferring substitutions in HCV genotypes 1 to 6 that were identified for other NS5A inhibitors, including those at key amino acid positions 28, 30, 31, or 93. The combination of pibrentasvir with HCV inhibitors of other classes produced synergistic inhibition of HCV replication. In summary, pibrentasvir is a next-generation HCV NS5A inhibitor with potent and pan-genotypic activity, and it maintains activity against common amino acid substitutions of HCV genotypes 1 to 6 that are known to confer resistance to currently approved NS5A inhibitors. Copyright © 2017 Ng et al.

Cellular Accumulation and Pharmacodynamic Evaluation of the Intracellular Activity of CEM-101, a Novel Fluoroketolide, against Staphylococcus aureus, Listeria monocytogenes, and Legionella pneumophila in Human THP-1 Macrophages ▿ †

PubMed Central

Lemaire, Sandrine; Van Bambeke, Françoise; Tulkens, Paul M.

2009-01-01

CEM-101 is a novel fluoroketolide with lower MICs than those of telithromycin and macrolides. Our aim was to assess the cellular accumulation and intracellular activity of CEM-101 using models developed for analyzing the pharmacokinetics and pharmacological properties of antibiotics against phagocytized bacteria. We used THP-1 macrophages and Staphylococcus aureus (ATCC 25923 [methicillin (meticillin) sensitive]), Listeria monocytogenes (strain EGD), and Legionella pneumophila (ATCC 33153). CEM-101 reached cellular-to-extracellular-concentration ratios of about 350 within 24 h (versus approximately 20, 30, and 160 for telithromycin, clarithromycin, and azithromycin, respectively). This intracellular accumulation was suppressed by incubation at a pH of ≤6 and by monensin (proton ionophore) and was unaffected by verapamil (P-glycoprotein inhibitor; twofold accumulation increase for azithromycin) or gemfibrozil. While keeping with the general properties of the macrolide antibiotics in terms of maximal efficacy (Emax; approximately 1-log10-CFU decrease compared to the postphagocytosis inoculum after a 24-h incubation), CEM-101 showed significantly greater potency against phagocytized S. aureus than telithromycin, clarithromycin, and azithromycin (for which the 50% effective concentration [EC50] and static concentrations were about 3-, 6-, and 15-fold lower, respectively). CEM-101 was also about 50-fold and 100-fold more potent than azithromycin against phagocytized L. monocytogenes and L. pneumophila, respectively. These differences in EC50s and static concentrations between drugs were minimized when data were expressed as multiples of the MIC, demonstrating the critical role of intrinsic drug activity (MIC) in eliciting the antibacterial intracellular effects, whereas accumulation per se was unimportant. CEM-101 should show enhanced in vivo potency if used at doses similar to those of the comparators tested here. PMID:19564365

Cellular accumulation and pharmacodynamic evaluation of the intracellular activity of CEM-101, a novel fluoroketolide, against Staphylococcus aureus, Listeria monocytogenes, and Legionella pneumophila in human THP-1 macrophages.

PubMed

Lemaire, Sandrine; Van Bambeke, Françoise; Tulkens, Paul M

2009-09-01

CEM-101 is a novel fluoroketolide with lower MICs than those of telithromycin and macrolides. Our aim was to assess the cellular accumulation and intracellular activity of CEM-101 using models developed for analyzing the pharmacokinetics and pharmacological properties of antibiotics against phagocytized bacteria. We used THP-1 macrophages and Staphylococcus aureus (ATCC 25923 [methicillin (meticillin) sensitive]), Listeria monocytogenes (strain EGD), and Legionella pneumophila (ATCC 33153). CEM-101 reached cellular-to-extracellular-concentration ratios of about 350 within 24 h (versus approximately 20, 30, and 160 for telithromycin, clarithromycin, and azithromycin, respectively). This intracellular accumulation was suppressed by incubation at a pH of < or = 6 and by monensin (proton ionophore) and was unaffected by verapamil (P-glycoprotein inhibitor; twofold accumulation increase for azithromycin) or gemfibrozil. While keeping with the general properties of the macrolide antibiotics in terms of maximal efficacy (Emax; approximately 1-log10-CFU decrease compared to the postphagocytosis inoculum after a 24-h incubation), CEM-101 showed significantly greater potency against phagocytized S. aureus than telithromycin, clarithromycin, and azithromycin (for which the 50% effective concentration [EC50] and static concentrations were about 3-, 6-, and 15-fold lower, respectively). CEM-101 was also about 50-fold and 100-fold more potent than azithromycin against phagocytized L. monocytogenes and L. pneumophila, respectively. These differences in EC50s and static concentrations between drugs were minimized when data were expressed as multiples of the MIC, demonstrating the critical role of intrinsic drug activity (MIC) in eliciting the antibacterial intracellular effects, whereas accumulation per se was unimportant. CEM-101 should show enhanced in vivo potency if used at doses similar to those of the comparators tested here.

Conceptuation, formulation and evaluation of sustained release floating tablets of captopril compression coated with gastric dispersible hydrochlorothiazide using 23 factorial design

PubMed Central

Sirisha, Pathuri Lakshmi; Babu, Govada Kishore; Babu, Puttagunta Srinivasa

2014-01-01

Ambulatory blood pressure monitoring is regarded as the gold standard for hypertensive therapy in non-dipping hypertension patients. A novel compression coated formulation of captopril and hydrochlorothiazide (HCTZ) was developed in order to improve the efficacy of antihypertensive therapy considering the half-life of both drugs. The synergistic action using combination therapy can be effectively achieved by sustained release captopril (t1/2= 2.5 h) and fast releasing HCTZ (average t1/2= 9.5 h). The sustained release floating tablets of captopril were prepared by using 23 factorial design by employing three polymers i.e., ethyl cellulose (EC), carbopol and xanthan gum at two levels. The formulations (CF1-CF8) were optimized using analysis of variance for two response variables, buoyancy and T50%. Among the three polymers employed, the coefficients and P values for the response variable buoyancy and T50% using EC were found to be 3.824, 0.028 and 0.0196, 0.046 respectively. From the coefficients and P values for the two response variables, formulation CF2 was optimized, which contains EC polymer alone at a high level. The CF2 formulation was further compression coated with optimized gastric dispersible HCTZ layer (HF9). The compression coated tablet was further evaluated using drug release kinetics. The Q value of HCTZ layer is achieved within 20 min following first order release whereas the Q value of captopril was obtained at 6.5 h following Higuchi model, from which it is proved that rapid release HCTZ and slow release of captopril is achieved. The mechanism of drug release was analyzed using Peppas equation, which showed an n >0.90 confirming case II transportation mechanism for drug release. PMID:25006552

Estimation of the toxicity of sulfadiazine to Daphnia magna using negligible depletion hollow-fiber liquid-phase microextraction independent of ambient pH

PubMed Central

Liu, Kailin; Xu, Shiji; Zhang, Minghuan; Kou, Yahong; Zhou, Xiaomao; Luo, Kun; Hu, Lifeng; Liu, Xiangying; Liu, Min; Bai, Lianyang

2016-01-01

The toxicity of ionizable organic compounds to organisms depends on the pH, which therefore affects risk assessments of these compounds. However, there is not a direct chemical method to predict the toxicity of ionizable organic compounds. To determine whether hollow-fiber liquid-phase microextraction (HF-LPME) is applicable for this purpose, a three-phase HF-LPME was used to measure sulfadiazine and estimate its toxicity to Daphnia magna in solutions of different pH. The result indicated that the sulfadiazine concentrations measured by HF-LPME decreased with increasing pH, which is consistent with the decreased toxicity. The concentration immobilize 50% of the daphnids (EC50) in 48 h calculated from nominal concentrations increased from 11.93 to 273.5 mg L−1 as the pH increased from 6.0 to 8.5, and the coefficient of variation (CV) of the EC50 values reached 104.6%. When calculated from the concentrations measured by HF-LPME (pH 12 acceptor phase), the EC50 ranged from 223.4 to 394.6 mg L−1, and the CV decreased to 27.60%, suggesting that the concentrations measured by HF-LPME can be used to estimate the toxicity of sulfadiazine irrespective of the solution pH. PMID:28004779

The toxicity of the three antifouling biocides DCOIT, TPBP and medetomidine to the marine pelagic copepod Acartia tonsa.

PubMed

Wendt, Ida; Backhaus, Thomas; Blanck, Hans; Arrhenius, Åsa

2016-07-01

Copepods, the largest group of pelagic grazers, are at risk from exposure to antifouling biocides. This study investigated the toxicity of the antifouling biocides 4,5-dichloro-2-octyl-1,2-thiazol-3(2H)-one (DCOIT), triphenylborane pyridine (TPBP) and 4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole (medetomidine) to the copepod Acartia tonsa, using mortality and egg production as endpoints. The toxicity ranking for mortality was as follows: DCOIT (LC50 57 nmol l(-1)) = TPBP (LC50 56 nmol l(-1)) > medetomidine (LC50 241 nmol l(-1)). Egg production was more sensitive than mortality to TPBP (EC50 3.2 nmol l(-1)), while DCOIT and medetomidine inhibited egg production at roughly the same concentrations (72 and 186 nmol l(-1) respectively). Furthermore, TPBP seems to affect egg hatching directly which was not the case for DCOIT and medetomidine. DCOIT and medetomidine might pose an environmental risk as they have been reported to occur in different exposure scenarios or analytical surveys at concentrations only 2-3 times lower than the respective EC10. Reported environmental concentrations of TPBP are few but clearly lower than the EC10 values reported here, suggesting current risk of TPBP to copepods to be moderate.

Growth of Listeria monocytogenes, Salmonella spp., Escherichia coli O157:H7, and Staphylococcus aureus on cheese during extended storage at 25°C.

PubMed

Leong, Wan Mei; Geier, Renae; Engstrom, Sarah; Ingham, Steve; Ingham, Barbara; Smukowski, Marianne

2014-08-01

Potentially hazardous foods require time/temperature control for safety. According to the U.S. Food and Drug Administration Food Code, most cheeses are potentially hazardous foods based on pH and water activity, and a product assessment is required to evaluate safety of storage >6 h at 21°C. We tested the ability of 67 market cheeses to support growth of Listeria monocytogenes (LM), Salmonella spp. (SALM), Escherichia coli O157:H7 (EC), and Staphylococcus aureus (SA) over 15 days at 25°C. Hard (Asiago and Cheddar), semi-hard (Colby and Havarti), and soft cheeses (mozzarella and Mexican-style), and reduced-sodium or reduced-fat types were tested. Single-pathogen cocktails were prepared and individually inoculated onto cheese slices (∼10(5) CFU/g). Cocktails were 10 strains of L. monocytogenes, 6 of Salmonella spp., or 5 of E. coli O157:H7 or S. aureus. Inoculated slices were vacuum packaged and stored at 25°C for ≤ 15 days, with surviving inocula enumerated every 3 days. Percent salt-in-the-moisture phase, percent titratable acidity, pH, water activity, and levels of indigenous/starter bacteria were measured. Pathogens did not grow on 53 cheeses, while 14 cheeses supported growth of SA, 6 of SALM, 4 of LM, and 3 of EC. Of the cheeses supporting pathogen growth, all supported growth of SA, ranging from 0.57 to 3.08 log CFU/g (average 1.70 log CFU/g). Growth of SALM, LM, and EC ranged from 1.01 to 3.02 log CFU/g (average 2.05 log CFU/g), 0.60 to 2.68 log CFU/g (average 1.60 log CFU/g), and 0.41 to 2.90 log CFU/g (average 1.69 log CFU/g), respectively. Pathogen growth varied within cheese types or lots. Pathogen growth was influenced by pH and percent salt-in-the-moisture phase, and these two factors were used to establish growth/no-growth boundary conditions for safe, extended storage (≤25°C) of pasteurized milk cheeses. Pathogen growth/no-growth could not be predicted for Swiss-style cheeses, mold-ripened or bacterial surface-ripened cheeses, and cheeses made with nonbovine milk, as insufficient data were gathered. This challenge study data can support science-based decision making in a regulatory framework.

Enzyme catalysis-electrophoresis titration for multiplex enzymatic assay via moving reaction boundary chip.

PubMed

Zhong, Ran; Xie, Haiyang; Kong, Fanzhi; Zhang, Qiang; Jahan, Sharmin; Xiao, Hua; Fan, Liuyin; Cao, Chengxi

2016-09-21

In this work, we developed the concept of enzyme catalysis-electrophoresis titration (EC-ET) under ideal conditions, the theory of EC-ET for multiplex enzymatic assay (MEA), and a related method based on a moving reaction boundary (MRB) chip with a collateral channel and cell phone imaging. As a proof of principle, the model enzymes horseradish peroxidase (HRP), laccase and myeloperoxidase (MPO) were chosen for the tests of the EC-ET model. The experiments revealed that the EC-ET model could be achieved via coupling EC with ET within a MRB chip; particularly the MEA analyses of catalysis rate, maximum rate, activity, Km and Kcat could be conducted via a single run of the EC-ET chip, systemically demonstrating the validity of the EC-ET theory. Moreover, the developed method had these merits: (i) two orders of magnitude higher sensitivity than a fluorescence microplate reader, (ii) simplicity and low cost, and (iii) fairly rapid (30 min incubation, 20 s imaging) analysis, fair stability (<5.0% RSD) and accuracy, thus validating the EC-ET method. Finally, the developed EC-ET method was used for the clinical assay of MPO activity in blood samples; the values of MPO activity detected via the EC-ET chip were in agreement with those obtained by a traditional fluorescence microplate reader, indicating the applicability of the EC-ET method. The work opens a window for the development of enzymatic research, enzyme assay, immunoassay, and point-of-care testing as well as titration, one of the oldest methods of analysis, based on a simple chip.

Toxicity of Inorganic Mercury to Native Australian Grass Grown in Three Different Soils.

PubMed

Mahbub, Khandaker Rayhan; Kader, Mohammed; Krishnan, Kannan; Labbate, Maurizio; Naidu, Ravi; Megharaj, Mallavarapu

2017-06-01

In this study, three native Australian grasses namely Iseilema membranaceum (Barcoo), Dichanthium sericeum (Queensland Blue) and Sporobolus africanus (Tussock) were grown in three different soils spiked with different concentrations of inorganic mercury and the root elongation was monitored up to 28 days following the germination. Results showed that mercury at certain concentrations significantly inhibited the root growth of all three tested native grasses grown in three soils, however, the toxicity was less in the soil with high organic carbon content and acidic pH. The calculated EC 50 values ranged from 10 to 224 mg/kg total Hg in soil. However, the EC 10 values indicated that existing guideline values for mercury may be of protective to the native Australian vegetation. Considering their tolerance to soil mercury, these grass species have the potential for their use in rehabilitation of mercury contaminated sites.

Rilpivirine exposure in plasma and sanctuary site compartments after switching from nevirapine-containing combined antiretroviral therapy.

PubMed

Mora-Peris, Borja; Watson, Victoria; Vera, Jaime H; Weston, Rosy; Waldman, Adam D; Kaye, Steve; Khoo, Saye; Mackie, Nicola E; Back, David; Winston, Alan

2014-06-01

Pharmacokinetic parameters following modifications to antiretroviral therapy and sanctuary site exposure are often unknown for recently licensed antiretrovirals. We assessed plasma, CSF and seminal plasma (SP) exposure of rilpivirine after switching from nevirapine. HIV-infected male subjects receiving tenofovir/emtricitabine/nevirapine (245/200/400 mg) once daily switched to tenofovir/emtricitabine/rilpivirine (245/200/25 mg) once daily for 60 days when CSF and semen samples were collected. Mean and individual plasma concentrations of nevirapine and rilpivirine were compared with the proposed plasma target concentration for nevirapine (3000 ng/mL) and the protein binding-adjusted EC90 for rilpivirine (12.1 ng/mL). Mean rilpivirine CSF and SP concentrations were calculated and individual values compared with the EC50 and EC90 for wild-type virus (0.27 and 0.66 ng/mL, respectively). Of 13 subjects completing study procedures including CSF examination, 8 provided seminal samples. By day 3, the mean plasma rilpivirine trough concentration was 29.7 ng/mL (95% CI: 23.8-37). No patient presented rilpivirine plasma concentrations under the proposed threshold. The mean rilpivirine concentration in CSF was 0.8 ng/mL (95% CI: 0.7-1.0), representing a CSF : plasma ratio of 1.4%, with concentrations above the EC90 in 85% (11/13) of patients. In SP, the mean rilpivirine concentration was 4.9 ng/mL (95% CI: 3.3-7.2), representing an SP : plasma ratio of 9.5%, with all concentrations above the EC90. Switching from nevirapine- to rilpivirine-containing antiretroviral therapy was safe and well tolerated, with plasma rilpivirine concentrations above the protein binding-adjusted EC90 in all subjects. Rilpivirine concentrations were always above the EC50 in the CSF and the EC90 in SP. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Optimization of Supercritical Fluid Extraction of Total Alkaloids, Peimisine, Peimine and Peiminine from the Bulb of Fritillaria thunbergii Miq, and Evaluation of Antioxidant Activities of the Extracts

PubMed Central

Ruan, Xiao; Yang, Li; Cui, Wen-Xia; Zhang, Men-Xing; Li, Zhao-Hui; Liu, Ben; Wang, Qiang

2016-01-01

Supercritical fluid extraction (SFE) was used to extract total alkaloids, peimisine, peimine and peiminine from the bulb of Fritillaria thunbergii Miq. The antioxidant capacity of the extracts was evaluated by DPPH radical scavenging activity (DPPH-RSA), ABTS radical scavenging activity (ABTS-RSA) and ferric reducing capacity (FRAP) assay. A central composite design (CCD) with four variables and five levels was employed for optimization of process parameters, and response surface plots were constructed in accordance with a second order polynomial model. Under optimal conditions of 3.0 h, 60.4 °C, 26.5 MPa and 89.3% ethanol, the highest yields were predicted to be 3.8 mg/g for total alkaloids, 0.5 mg/g for peimisine, 1.3 mg/g for peimine and 1.3 mg/g for peiminine, and the antioxidant capacity of extracts displayed EC50, DPPH value of 5.5 mg/mL, EC50, ABTS value of 0.3 mg/mL and FRAP value of 118.2 mg ascorbic acid equivalent (AAE)/100 g. PMID:28773648

Radioligand binding and functional characterization of recombinant human NmU1 and NmU2 receptors stably expressed in clonal human embryonic kidney-293 cells.

PubMed

Aiyar, Nambi; Disa, Jyoti; Foley, James J; Buckley, Peter T; Wixted, William E; Pullen, Mark; Shabon, Usman; Dul, Edward; Szekeres, Philip G; Elshourbagy, Nabil A; Sarau, Henry M; Appelbaum, Edward; Bolaky, Jane

2004-09-01

Neuromedin U (NmU) is a smooth muscle contracting peptide. Recently, two G-protein-coupled receptors for NmU (NmU1R and NmU2R) have been cloned having approximately 50% homology. They have distinct patterns of expression suggesting they may have different biological functions. This study provides a comprehensive characterization of both NmU receptors expressed in human embryonic kidney 293 cells. [125I]hNmU binding to the recombinant NmU receptors was rapid, saturable, of high affinity and to a single population of binding sites. Exposure of these cells to NmU isopeptides resulted in an increase in intracellular [Ca2+]i release (EC50 value of 0.50 +/- 0.10 nmol/l) and inositol phosphate formation (EC50 1.6 +/- 0.2 and 1.50 +/- 0.4 nmol/l for NmU1R and NmU2R respectively). Furthermore, hNmU inhibited forskolin (3 micromol/l)-stimulated accumulation of cAMP in intact HEK-293 cells expressing either NmU1R or NmU2R. The inhibitory effect was significant for the cells expressing NmU2R with IC50 value of 0.80 +/- 0.21 nmol/l. In summary, both NmU1R and NmU2R in HEK-293 cells have similar signaling capability. Copyright 2004 S. Karger AG, Basel

Database search of spontaneous reports and pharmacological investigations on the sulfonylureas and glinides-induced atrophy in skeletal muscle

PubMed Central

Mele, Antonietta; Calzolaro, Sara; Cannone, Gianluigi; Cetrone, Michela; Conte, Diana; Tricarico, Domenico

2014-01-01

The ATP-sensitive K+ (KATP) channel is an emerging pathway in the skeletal muscle atrophy which is a comorbidity condition in diabetes. The “in vitro” effects of the sulfonylureas and glinides were evaluated on the protein content/muscle weight, fibers viability, mitochondrial succinic dehydrogenases (SDH) activity, and channel currents in oxidative soleus (SOL), glycolitic/oxidative flexor digitorum brevis (FDB), and glycolitic extensor digitorum longus (EDL) muscle fibers of mice using biochemical and cell-counting Kit-8 assay, image analysis, and patch-clamp techniques. The sulfonylureas were: tolbutamide, glibenclamide, and glimepiride; the glinides were: repaglinide and nateglinide. Food and Drug Administration-Adverse Effects Reporting System (FDA-AERS) database searching of atrophy-related signals associated with the use of these drugs in humans has been performed. The drugs after 24 h of incubation time reduced the protein content/muscle weight and fibers viability more effectively in FDB and SOL than in the EDL. The order of efficacy of the drugs in reducing the protein content in FDB was: repaglinide (EC50 = 5.21 × 10−6) ≥ glibenclamide(EC50 = 8.84 × 10−6) > glimepiride(EC50 = 2.93 × 10−5) > tolbutamide(EC50 = 1.07 × 10−4) > nateglinide(EC50 = 1.61 × 10−4) and it was: repaglinide(7.15 × 10−5) ≥ glibenclamide(EC50 = 9.10 × 10−5) > nateglinide(EC50 = 1.80 × 10−4) ≥ tolbutamide(EC50 = 2.19 × 10−4) > glimepiride(EC50=–) in SOL. The drug-induced atrophy can be explained by the KATP channel block and by the enhancement of the mitochondrial SDH activity. In an 8-month period, muscle atrophy was found in 0.27% of the glibenclamide reports in humans and in 0.022% of the other not sulfonylureas and glinides drugs. No reports of atrophy were found for the other sulfonylureas and glinides in the FDA-AERS. Glibenclamide induces atrophy in animal experiments and in human patients. Glimepiride shows less potential for inducing atrophy. PMID:25505577

Toxicity of nanoparticles of CuO, ZnO and TiO2 to microalgae Pseudokirchneriella subcapitata.

PubMed

Aruoja, Villem; Dubourguier, Henri-Charles; Kasemets, Kaja; Kahru, Anne

2009-02-01

Toxicities of ZnO, TiO2 and CuO nanoparticles to Pseudokirchneriella subcapitata were determined using OECD 201 algal growth inhibition test taking in account potential shading of light. The results showed that the shading effect by nanoparticles was negligible. ZnO nanoparticles were most toxic followed by nano CuO and nano TiO2. The toxicities of bulk and nano ZnO particles were both similar to that of ZnSO4 (72 h EC50 approximately 0.04 mg Zn/l). Thus, in this low concentration range the toxicity was attributed solely to solubilized Zn2+ ions. Bulk TiO2 (EC50=35.9 mg Ti/l) and bulk CuO (EC50=11.55 mg Cu/l) were less toxic than their nano formulations (EC50=5.83 mg Ti/l and 0.71 mg Cu/l). NOEC (no-observed-effect-concentrations) that may be used for risk assessment purposes for bulk and nano ZnO did not differ (approximately 0.02 mg Zn/l). NOEC for nano CuO was 0.42 mg Cu/l and for bulk CuO 8.03 mg Cu/l. For nano TiO2 the NOEC was 0.98 mg Ti/l and for bulk TiO2 10.1 mg Ti/l. Nano TiO2 formed characteristic aggregates entrapping algal cells that may contribute to the toxic effect of nano TiO2 to algae. At 72 h EC50 values of nano CuO and CuO, 25% of copper from nano CuO was bioavailable and only 0.18% of copper from bulk CuO. Thus, according to recombinant bacterial and yeast Cu-sensors, copper from nano CuO was 141-fold more bioavailable than from bulk CuO. Also, toxic effects of Cu oxides to algae were due to bioavailable copper ions. To our knowledge, this is one of the first systematic studies on effects of metal oxide nanoparticles on algal growth and the first describing toxic effects of nano CuO towards algae.

Derivation of guideline values for gold (III) ion toxicity limits to protect aquatic ecosystems.

PubMed

Nam, Sun-Hwa; Lee, Woo-Mi; Shin, Yu-Jin; Yoon, Sung-Ji; Kim, Shin Woong; Kwak, Jin Il; An, Youn-Joo

2014-01-01

This study focused on estimating the toxicity values of various aquatic organisms exposed to gold (III) ion (Au(3+)), and to propose maximum guideline values for Au(3+) toxicity that protect the aquatic ecosystem. A comparative assessment of methods developed in Australia and New Zealand versus the European Community (EC) was conducted. The test species used in this study included two bacteria (Escherichia coli and Bacillus subtilis), one alga (Pseudokirchneriella subcapitata), one euglena (Euglena gracilis), three cladocerans (Daphnia magna, Moina macrocopa, and Simocephalus mixtus), and two fish (Danio rerio and Oryzias latipes). Au(3+) induced growth inhibition, mortality, immobilization, and/or developmental malformations in all test species, with responses being concentration-dependent. According to the moderate reliability method of Australia and New Zealand, 0.006 and 0.075 mg/L of guideline values for Au(3+) were obtained by dividing 0.33 and 4.46 mg/L of HC5 and HC50 species sensitivity distributions (SSD) with an FACR (Final Acute to Chronic Ratio) of 59.09. In contrast, the EC method uses an assessment factor (AF), with the 0.0006 mg/L guideline value for Au(3+) being divided with the 48-h EC50 value for 0.60 mg/L (the lowest toxicity value obtained from short term results) by an AF of 1000. The Au(3+) guideline value derived using an AF was more stringent than the SSD. We recommend that more toxicity data using various bioassays are required to develop more accurate ecological risk assessments. More chronic/long-term exposure studies on sensitive endpoints using additional fish species and invertebrates not included in the current dataset will be needed to use other derivation methods (e.g., US EPA and Canadian Type A) or the "High Reliability Method" from Australia/New Zealand. Such research would facilitate the establishment of guideline values for various pollutants that reflect the universal effects of various pollutants in aquatic ecosystems. To the best of our knowledge, this is the first study to suggest guideline values for Au(3+) levels permitted to enter freshwater environments. Copyright © 2013 Elsevier Ltd. All rights reserved.

Evaluation of luciferase and GFP-expressing Nipah viruses for rapid quantitative antiviral screening.

PubMed

Lo, Michael K; Nichol, Stuart T; Spiropoulou, Christina F

2014-06-01

Nipah virus (NiV) outbreaks have occurred in Malaysia, India, and Bangladesh, and the virus continues to cause annual outbreaks of fatal human encephalitis in Bangladesh due to spillover from its bat host reservoir. Due to its high pathogenicity, its potential use for bio/agro-terrorism, and to the current lack of approved therapeutics, NiV is designated as an overlap select agent requiring biosafety level-4 containment. Although the development of therapeutic monoclonal antibodies and soluble protein subunit vaccines have shown great promise, the paucity of effective antiviral drugs against NiV merits further exploration of compound libraries using rapid quantitative antiviral assays. As a proof-of-concept study, we evaluated the use of fluorescent and luminescent reporter NiVs for antiviral screening. We constructed and rescued NiVs expressing either Renilla luciferase or green fluorescent protein, and characterized their reporter signal kinetics in different cell types as well as in the presence of several inhibitors. The 50% effective concentrations (EC50s) derived for inhibitors against both reporter viruses are within range of EC50s derived from virus yield-based dose-response assays against wild-type NiV (within 1Log10), thus demonstrating that both reporter NiVs can serve as robust antiviral screening tools. Utilizing these live NiV-based reporter assays requires modest instrumentation, and circumvents the time and labor-intensive steps associated with cytopathic effect or viral antigen-based assays. These reporter NiVs will not only facilitate antiviral screening, but also the study of host cell components that influence the virus life cycle. Published by Elsevier B.V.

Application of calcium oxide (CaO, heated scallop-shell powder) for the reduction of Listeria monocytogenes biofilms on eggshell surfaces.

PubMed

Park, S Y; Jung, S-J; Kang, I; Ha, S-D

2018-05-01

This study investigated bactericidal activity of 0.05 to 0.50% calcium oxide (CaO) against planktonic cells in tryptic soy broth (TSB) and biofilms of Listeria monocytogenes on eggshell surfaces. The bactericidal activity of CaO against planktonic cells and biofilms of L. monocytogens significantly (P < 0.05) increased log reductions with increasing concentrations of CaO. Exposure to 0.05 to 0.50% CaO for one min reduced planktonic cells in TSB cell suspensions by 0.47 to 3.86 log10CFU/mL and biofilm cells on the shell surfaces by 0.14 to 2.32 log10CFU/cm2. The Hunter colors of eggshells ("L" for lightness, "a" for redness, and "b" for yellowness), shell thickness (puncture force), and sensory quality (egg taste and yolk color) were not changed by 0.05 to 0.50% CaO treatment. The nonlinear Weibull model was used to calculate CR = 3 values as the CaO concentration of 3 log (99.9%) reduction for planktonic cells (R2 = 0.96, RMSE = 0.26) and biofilms (R2 = 0.95, RMSE = 0.18) of L. monocytogens. The CR = 3 value, 0.31% CaO for planktonic cells, was significantly (P < 0.05) lower than 0.57% CaO for biofilms. CaO could be an alternative disinfectant to reduce planktonic cells and biofilms L. monocytogenes on eggshell surface in egg processing plants.

The use of reference materials in quality assurance programmes in food microbiology laboratories.

PubMed

In't Veld, P H

1998-11-24

Nine different reference materials (RMs) for use in food and water microbiology have been developed with the support of the European Commission (EC). The production process of RMs is based on spray drying bacteria suspended in milk. The highly contaminated milk powder (HCMP) obtained is mixed with sterile milk powder to achieve the desired level of contamination and is subsequently filled into gelatine capsules. The HCMP may need to be stabilised by storage for more than a year before a stable RM can be prepared. The HCMP are mixed with sterile milk powder using a pestle and mortar in order to produce homogeneous RMs. For routine use of RMs Shewhart control charts can be produced. Based on log10 transformed counts, control limits are calculated. Rules for the interpretation of results facilitate the detection of out of control situations. Besides RMs there are also CRMs (Certified Reference Materials) that are certified by the EC Community Bureau of Reference (BCR) and are intended for occasional use. Based on the BCR certificate, user tables are produced presenting the 95% confidence limits for the number of capsules likely to be examined in practice. Also power analysis is made to indicate the minimum difference between the certified value and the observed geometric mean value in relation to the number of capsules examined.

40 CFR 158.630 - Terrestrial and aquatic nontarget organisms data requirements table.

Code of Federal Regulations, 2010 CFR

2010-07-01

... LC50, two avian reproduction studies, two freshwater fish LC50, one freshwater invertebrate EC50, one honeybee acute contact LD50, one freshwater fish early-life stage, one freshwater invertebrate life cycle, and three estuarine acute LC50/EC50 studies -- fish, mollusk and invertebrate. All other outdoor...

Determining chewing efficiency using a solid test food and considering all phases of mastication.

PubMed

Liu, Ting; Wang, Xinmiao; Chen, Jianshe; van der Glas, Hilbert W

2018-07-01

Following chewing a solid food, the median particle size, X 50 , is determined after N chewing cycles, by curve-fitting of the particle size distribution. Reduction of X 50 with N is traditionally followed from N ≥ 15-20 cycles when using the artificial test food Optosil ® , because of initially unreliable values of X 50 . The aims of the study were (i) to enable testing at small N-values by using initial particles of appropriate size, shape and amount, and (ii) to compare measures of chewing ability, i.e. chewing efficiency (N needed to halve the initial particle size, N(1/2-Xo)) and chewing performance (X 50 at a particular N-value, X 50,N ). 8 subjects with a natural dentition chewed 4 types of samples of Optosil particles: (1) 8 cubes of 8 mm, border size relative to bin size (traditional test), (2) 9 half-cubes of 9.6 mm, mid-size; similar sample volume, (3) 4 half-cubes of 9.6 mm, and 2 half-cubes of 9.6 mm; reduced particle number and sample volume. All samples were tested with 4 N-values. Curve-fitting with a 2nd order polynomial function yielded log(X 50 )-log(N) relationships, after which N(1/2-Xo) and X 50,N were obtained. Reliable X 50 -values are obtained for all N-values when using half-cubes with a mid-size relative to bin sizes. By using 2 or 4 half-cubes, determination of N(1/2-Xo) or X 50,N needs less chewing cycles than traditionally. Chewing efficiency is preferable over chewing performance because of a comparison of inter-subject chewing ability at the same stage of food comminution and constant intra-subject and inter-subject ratios between and within samples respectively. Copyright © 2018 Elsevier Ltd. All rights reserved.

Genotoxic and cytotoxic effects of ZnO nanoparticles for Dunaliella tertiolecta and comparison with SiO2 and TiO2 effects at population growth inhibition levels.

PubMed

Schiavo, S; Oliviero, M; Miglietta, M; Rametta, G; Manzo, S

2016-04-15

The increasing use of oxide nanoparticles (NPs) in commercial products has intensified the potential release into the aquatic environment where algae represent the basis of the trophic chain. NP effects upon algae population growth were indeed already reported in literature, but the concurrent effects at cellular and genomic levels are still largely unexplored. Our work investigates the genotoxic (by COMET assay) and cytotoxic effects (by qualitative ROS production and cell viability) of ZnO nanoparticles toward marine microalgae Dunaliella tertiolecta. A comparison at defined population growth inhibition levels (i.e. 50% Effect Concentration, EC50, and No Observed Effect Concentration, NOEC) with SiO2 and TiO2 genotoxic effects and previously investigated cytotoxic effects (Manzo et al., 2015) was performed in order to elucidate the possible diverse mechanisms leading to algae growth inhibition. After 72h exposure, ZnO particles act firstly at the level of cell division inhibition (EC50: 2mg Zn/L) while the genotoxic action is evident only starting from 5mg Zn/L. This outcome could be ascribable mainly to the release of toxic ions from the aggregate of ZnO particle in the proximity of cell membrane. In the main, at EC50 and NOEC values for ZnO NPs showed the lowest cytotoxic and genotoxic effect with respect to TiO2 and SiO2. Based on Mutagenic Index (MI) the rank of toxicity is actually: TiO2>SiO2>ZnO with TiO2 and SiO2 that showed similar MI values at both NOEC and EC50 concentrations. The results presented herein suggest that up to TiO2 NOEC (7.5mg/L), the algae DNA repair mechanism is efficient and the DNA damage does not result in an evident algae population growth inhibition. A similar trend for SiO2, although at lower effect level with respect to TiO2, is observable. The comparison among all the tested nanomaterial toxicity patterns highlighted that the algae population growth inhibition occurred through pathways specific for each NP also related to their different physicochemical behaviors in seawater. Copyright © 2016 Elsevier B.V. All rights reserved.

Characterization of postharvest fungicide-resistant Botrytis cinerea isolates from commercially stored apple fruit

USDA-ARS?s Scientific Manuscript database

Botrytis cinerea causes grey mold of apple fruit and is one of the most economically important postharvest pathogens of global concern. Eight fludioxonil sensitive B. cinerea isolates from Pennsylvania had EC50 values ranging from 0.004 to 0.0038 µg/ml fludioxonil that were dual resistant to pyrimet...

Phytochemical investigations and antioxidant potential of roots of Leea macrophylla (Roxb.).

PubMed

Mahmud, Zobaer Al; Bachar, Sitesh C; Hasan, Choudhury Mahmood; Emran, Talha Bin; Qais, Nazmul; Uddin, Mir Muhammad Nasir

2017-07-06

Oleanolic acid (NZ-15), 7 α, 28-olean diol (NZ-38) and Stigmasterol (NZ-14) were isolated from the ethanolic extracts of the roots of Leea macrophylla (Family: Leeaceae) by using chromatographic analysis. This is the first report of isolation of these compounds from this plant. Their structures were constructed by spectroscopic analysis and by comparing the data with the published one. Subsequently the ethanolic extract was fractionated with two organic solvents and all the fractions were studied to evaluate their in vitro antioxidant property. The ethanolic extract was fractionated with two organic solvents and all the fractions were studied to evaluate their in vitro antioxidant property by DPPH free radical scavenging assay, superoxide anion radical scavenging assay, nitric oxide radical scavenging assay, and reducing power assay. In the DPPH free radical scavenging assay and superoxide radical scavenging assay, the ethyl acetate soluble fraction of ethanolic extract revealed the highest free radical scavenging activity with IC 50 value of 2.65 and 155.62 μg/ml, respectively as compared to standard ascorbic acid (IC 50 value of 5.8 and 99.66 μg/ml). Ethyl acetate fraction also possessed highest reducing power activity with an EC50 value of 15.27 μg/ml compared to ascorbic acid (EC 50 0.91 μg/ml). On the other hand, the carbon tetrachloride fraction exhibited most significant NO scavenging activity with IC 50 value of 277.8 μg/ml that was even higher than that of standard ascorbic acid (IC 50 value 356.04 μg/ml). In addition, the total phenolic contents of these extract and fractions were evaluated using Folin-Ciocalteu reagent and varied from 7.93 to 50.21 mg/g dry weight expressed as gallic acid equivalents (GAE). This study showed that different extracts of roots of L. macrophylla possess potential DPPH, superoxide, and NO free radical scavenging activities. The antioxidant activities of the plant extracts might be due to the presence of oleanolic acid, oleanolic acid derivative 7 α, 28-olean diol and stigmasterol.

Ovicidal and larvicidal activity of extracts of Opuntia ficus-indica against gastrointestinal nematodes of naturally infected sheep.

PubMed

Féboli, Aline; Laurentiz, Antonio C; Soares, Suelen C S; Augusto, Jeferson G; Anjos, Luciano A; Magalhães, Lizandra G; Filardi, Rosemeire S; Laurentiz, Rosangela S

2016-08-15

This study describes the in vitro anthelmintic activity of extracts from Opuntia ficus indica against gastrointestinal nematodes of sheep. The anthelmintic activity was evaluated by inhibition of egg hatching, larval development and larval migration assays. The residual aqueous fractions from cladodes and fruits showed higher ovicidal activity with EC50 values of 7.2mg/mL and 1.5mg/mL, respectively. The aqueous, hexane, and ethyl acetate fractions from fruits and the aqueous fraction from cladodes inhibited 100% of larval development at the lowest concentration tested (1.56mg/mL). The crude cladode and fruit ethanolic extracts inhibited larval migration and showed EC50 values of 0.74mg/mL and 0.27mg/mL, respectively. Phytochemical screening detected high concentrations of alkaloids, tannins, flavonoids, and saponins in the fruits and cladodes. The results demonstrated that O. ficus exhibits anthelmintic activity in vitro, suggesting that, beyond its nutritional potential, this plant can also be an ally for parasite control in sheep. Copyright © 2016 Elsevier B.V. All rights reserved.

A BSL-4 high-throughput screen identifies sulfonamide inhibitors of Nipah virus.

PubMed

Tigabu, Bersabeh; Rasmussen, Lynn; White, E Lucile; Tower, Nichole; Saeed, Mohammad; Bukreyev, Alexander; Rockx, Barry; LeDuc, James W; Noah, James W

2014-04-01

Nipah virus is a biosafety level 4 (BSL-4) pathogen that causes severe respiratory illness and encephalitis in humans. To identify novel small molecules that target Nipah virus replication as potential therapeutics, Southern Research Institute and Galveston National Laboratory jointly developed an automated high-throughput screening platform that is capable of testing 10,000 compounds per day within BSL-4 biocontainment. Using this platform, we screened a 10,080-compound library using a cell-based, high-throughput screen for compounds that inhibited the virus-induced cytopathic effect. From this pilot effort, 23 compounds were identified with EC50 values ranging from 3.9 to 20.0 μM and selectivities >10. Three sulfonamide compounds with EC50 values <12 μM were further characterized for their point of intervention in the viral replication cycle and for broad antiviral efficacy. Development of HTS capability under BSL-4 containment changes the paradigm for drug discovery for highly pathogenic agents because this platform can be readily modified to identify prophylactic and postexposure therapeutic candidates against other BSL-4 pathogens, particularly Ebola, Marburg, and Lassa viruses.

A BSL-4 High-Throughput Screen Identifies Sulfonamide Inhibitors of Nipah Virus

PubMed Central

Tigabu, Bersabeh; Rasmussen, Lynn; White, E. Lucile; Tower, Nichole; Saeed, Mohammad; Bukreyev, Alexander; Rockx, Barry; LeDuc, James W.

2014-01-01

Abstract Nipah virus is a biosafety level 4 (BSL-4) pathogen that causes severe respiratory illness and encephalitis in humans. To identify novel small molecules that target Nipah virus replication as potential therapeutics, Southern Research Institute and Galveston National Laboratory jointly developed an automated high-throughput screening platform that is capable of testing 10,000 compounds per day within BSL-4 biocontainment. Using this platform, we screened a 10,080-compound library using a cell-based, high-throughput screen for compounds that inhibited the virus-induced cytopathic effect. From this pilot effort, 23 compounds were identified with EC50 values ranging from 3.9 to 20.0 μM and selectivities >10. Three sulfonamide compounds with EC50 values <12 μM were further characterized for their point of intervention in the viral replication cycle and for broad antiviral efficacy. Development of HTS capability under BSL-4 containment changes the paradigm for drug discovery for highly pathogenic agents because this platform can be readily modified to identify prophylactic and postexposure therapeutic candidates against other BSL-4 pathogens, particularly Ebola, Marburg, and Lassa viruses. PMID:24735442

C-glycoside mimetics inhibit glioma stem cell proliferation, migration, and invasion.

PubMed

Clarion, Ludovic; Jacquard, Carine; Sainte-Catherine, Odile; Decoux, Marc; Loiseau, Séverine; Rolland, Marc; Lecouvey, Marc; Hugnot, Jean-Philippe; Volle, Jean-Noël; Virieux, David; Pirat, Jean-Luc; Bakalara, Norbert

2014-10-23

This paper reports the design and synthesis of C-glycoside mimetics (d-glycero-d-talo- and d-glycero-d-galactopyranose analogues), a subset of the recently published phostines, belonging to the [1,2]oxaphosphinane core. Eighteen new compounds were tested against 11 cancer cell types belonging to six categories of tumor tissues and three different species. The hit compound 5.3d inhibited invasion and migration of both GBM stem cells (Gli7 and Gli4) and GBM cancer cell lines (C6, SNB75) on fibronectin, vitronectin, and laminin. Ki values for Gli7 and Gli4 migration inhibition on fibronectin were 16 and 31 nM respectively. Ki values for invasion inhibition in a 3D system were 46 nM for Gli7 and 290 nM for Gli4. These activities were associated with an antiproliferative effect on Gli4 (EC50 = 5.20 μM) and Gli7 (EC50 = 2.33 μM). In conclusion, the heptopyranose mimetic 5.3d, devoid of toxicity on astrocyte and cortical neuron cultures at concentrations below 100 μM, opens new therapeutic perspectives against glioblastoma.

Opportunities to use bark polyphenols in specialty chemical markets

Treesearch

Richard W. Hemingway

1998-01-01

Current forestry practice in North America is to transport pulpwood and logs from the harvest site to the mill with the bark on the wood. Approximately 18 percent of the weight of logs from conifers such as southern pine is bark. The majority of this bark is burned as hog fuel, but its fuel value is low. When compared with natural gas at an average of $2.50/MBTU or...

Relation of an Echocardiographic-Based Cardiac Calcium Score to Mitral Stenosis Severity and Coronary Artery Disease in Patients with Severe Aortic Stenosis.

PubMed

Sheng, Siyuan P; Howell, Lucius A; Caughey, Melissa C; Yeung, Michael; Vavalle, John P

2018-01-15

Patients with calcific aortic stenosis (AS) often have diffuse cardiac calcification involving the mitral valve apparatus and coronary arteries. We examined the association between global cardiac calcification quantified by a previously validated echocardiographic calcium score (eCS) with the severity of mitral stenosis (MS) and coronary artery disease (CAD) in patients with a clinical diagnosis of severe calcific AS. In this sample of 147 patients (mean age 81 ± 9 years, 50% male), 81 patients (55%) were determined by echocardiography to have some degree of MS. Higher mean eCS was observed in patients with more severe MS (r = 0.54, p < 0.0001). Higher eCS was also inversely associated with mitral valve area (r = -0.31, p = 0.001) and positively associated with mitral valve mean pressure gradient (r = 0.46, p < 0.0001) and mitral valve peak flow velocity (r = 0.55, p < 0.0001). The area under the receiver operating characteristic curve for using eCS to predict the presence of MS was 0.76. An eCS ≥ 8 predicted MS with a sensitivity of 68%, specificity of 76%, positive predictive value of 77%, and negative predictive value of 66%. High eCS, relative to low eCS, was associated with 2.70 times the adjusted odds of CAD (odds ratio = 2.70, 95% confidence interval 1.02 to 7.17). In conclusion, global cardiac calcification is associated with MS and CAD in patients with severe calcific AS, and eCS shows ability to predict the presence of MS. This study suggests that a simple eCS may be used as part of a risk-stratification tool in patients with severe calcific aortic valve stenosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Species differences in the negative inotropic effect of acetylcholine and soman in rat, guinea pig, and rabbit hearts. (Reannouncement with new availability information)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maxwell, D.M.; Thomsen, R.H.; Baskin, S.I.

1991-12-31

Acetylcholine reduced atrial contractions by 82.5% in guinea pig, 50.8% in rat, and 41.5% in rabbit. 2. The EC50, values for the negative inotropic effect of acetylcholine were 3.3 x 10(-7) M in rat and guinea pig atria and 4.1 x 10(-6) M in rabbit atria. 3. There was no correlation between the species differences in the negative inotropic effect of acetylcholine in atria and the density or affinity of acetylcholinesterase or muscarinic receptors. 4. Inhibition of atrial acetylcholinesterase with soman reduced the EC50 of acetylcholine three-fold in all species, but did not change the maximal inotropic effect of acetylcholine.more » 5. Species differences in the negative inotropic effect of acetylcholine may be caused by differences in the coupling between myocardial muscarinic receptors and the ion channels that mediate negative inotropy. Acetylcholine, cardiovascular response, species variation negative inotropic response.« less

Effect of thiopental sodium on N-methyl-D-aspartate-gated currents.

PubMed

Liu, Hongliang; Dai, Tijun; Yao, Shanglong

2006-05-01

N-methyl-D-aspartate (NMDA) receptors in the prefrontal cortex (PFC) are closely related with the excitability of pyramidal neurons and PFC function. As the effect of thiopental sodium on the central nervous system may partly result from the inhibition of PFC NMDA receptors, we investigated the effect of thiopental sodium with different concentrations on NMDA-gated currents in acutely dissociated rat PFC pyramidal neurons. We sought to determine whether thiopental sodium inhibits NMDA receptor function. Three to four week old male Sprague-Dawley rats were sacrificed and the PFC was dissected. Pyramidal neurons from the PFC were prepared and standard whole-cell patch clamp recordings were performed. Escalating concentrations from 3-1000 microM NMDA were applied 100 microm from the pyramidal cells, and the concentration in the effect compartment related to 50% effect (EC50) of NMDA was determined for the ensuing experiments. One hundred microM NMDA alone (control) or NMDA with different concentrations (10-1000 microM) of thiopental sodium were applied. After the inhibitory concentration, in 50% of NMDA effect (IC50) of thiopental sodium was established this IC50 and NMDA 3-1000 microM were applied 100 microm from the pyramidal cells. The EC50 value of NMDA under the effect of IC50 thiopental sodium was determined. N-methyl-D-aspartate induced inward currents in a concentration-dependent manner, which were completely antagonized by 50 microM AP5. The maximal amplitude of NMDA-induced current was 1.15 +/- 0.27 nA. The EC50 of NMDA was 53.6 +/- 12.4 microM. The NMDA (100 microM)-gated current was inhibited by thiopental sodium in a concentration-dependent manner, and the IC50 of thiopental sodium was 33.6 +/- 6.1 microM. Under the effect of 33.6 microM thiopental sodium, the maximal amplitude of NMDA-induced current was 0.87 +/- 0.17 nA. The concentration-response curve of NMDA was shifted rightwards. The EC50 of NMDA was 128 +/- 15 microM, which was greater than that of NMDA without thiopental sodium (P < 0.01). Thiopental sodium decreases NMDA-gated currents in acutely dissociated rat prefrontal cortical pyramidal neurons in a concentration-dependent manner.

Thresholds of arsenic toxicity to Eisenia fetida in field-collected agricultural soils exposed to copper mining activities in Chile.

PubMed

Bustos, Víctor; Mondaca, Pedro; Verdejo, José; Sauvé, Sébastien; Gaete, Hernán; Celis-Diez, Juan L; Neaman, Alexander

2015-12-01

Several previous studies highlighted the importance of using field-collected soils-and not artificially-contaminated soils-for ecotoxicity tests. However, the use of field-collected soils presents several difficulties for interpretation of results, due to the presence of various contaminants and unavoidable differences in the physicochemical properties of the tested soils. The objective of this study was to estimate thresholds of metal toxicity in topsoils of 24 agricultural areas historically contaminated by mining activities in Chile. We performed standardized earthworm reproduction tests (OECD 222 and ISO 11268-2) with Eisenia fetida. Total soil concentrations of Cu, As, Zn, and Pb were in the ranges of 82-1295 mg kg(-1), 7-41 mg kg(-1), 86-345 mg kg(-1), and 25-97 mg kg(-1), respectively. In order to differentiate between the effects of different metals, we used regression analysis between soil metal concentrations and earthworm responses, as well as between metal concentrations in earthworm tissues and earthworm responses. Based on regression analysis, we concluded that As was a metal of prime concern for Eisenia fetida in soils affected by Cu mining activities, while Cu exhibited a secondary effect. In contrast, the effects of Zn and Pb were not significant. Soil electrical conductivity was another significant contributor to reproduction toxicity in the studied soils, forcing its integration in the interpretation of the results. By using soils with electrical conductivity ≤ 0.29 dS m(-1) (which corresponds to EC50 of salt toxicity to Eisenia fetida), it was possible to isolate the effect of soil salinity on earthworm reproduction. Despite the confounding effects of Cu, it was possible to determine EC10, EC25 and EC50 values for total soil As at 8 mg kg(-1), 14 mg kg(-1) and 22 mg kg(-1), respectively, for the response of the cocoon production. However, it was not possible to determine these threshold values for juvenile production. Likewise, we were able to determine EC10, EC25 and EC50 of earthworm tissue As of 38 mg kg(-1), 47 mg kg(-1), and 57 mg kg(-1), respectively, for the response of the cocoon production. Finally, we determined the no-observed effect concentration of tissue As in E. fetida of 24 mg kg(-1). Thus, earthworm reproduction test is applicable for assessment of metal toxicity in field-collected soils with low electrical conductivity, while it might have a limited applicability in soils with high electrical conductivity because the salinity-induced toxicity will hinder the interpretation of the results. Copyright © 2015 Elsevier Inc. All rights reserved.

Universal screening of both endometrial and colon cancers increases the detection of Lynch syndrome.

PubMed

Adar, Tomer; Rodgers, Linda H; Shannon, Kristen M; Yoshida, Makoto; Ma, Tianle; Mattia, Anthony; Lauwers, Gregory Y; Iafrate, Anthony J; Hartford, Nicole M; Oliva, Esther; Chung, Daniel C

2018-05-11

Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC) and endometrial cancer (EC). Screening of all CRCs for LS is currently recommended, but screening of ECs is inconsistent. The objective of this study was to determine the added value of screening both CRC and EC tumors in the same population. A prospective, immunohistochemistry (IHC)-based screening program for all patients with newly diagnosed CRCs and ECs was initiated in 2011 and 2013, respectively, at 2 centers (primary and tertiary). Genetic testing was recommended for those who had tumors with absent mutS homolog 2 (MSH2), MSH6, or postmeiotoic segregation increased 2 (PMS2) expression and for those who had tumors with absent mutL homolog 1 (MLH1) expression and no v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation or MLH1 promoter methylation. Amsterdam II criteria, revised Bethesda criteria, and scores from prediction models for gene mutations (the PREMM 1,2,6 and PREMM 5 prediction models) were ascertained in patients with LS. In total, 1290 patients with CRC and 484 with EC were screened for LS, and genetic testing was recommended for 137 patients (10.6%) and 32 patients (6.6%), respectively (P = .01). LS was identified in 16 patients (1.2%) with CRC and in 8 patients (1.7%) with EC. Among patients for whom genetic testing was recommended, the LS diagnosis rate was higher among those with EC (25.0% vs 11.7%, P = .052). The Amsterdam II criteria, revised Bethesda criteria, and both PREMM calculators would have missed 62.5%, 50.0%, and 12.5% of the identified patients with LS, respectively. Expanding a universal screening program for LS to include patients who had EC identified 50% more patients with LS, and many of these patients would have been missed by risk assessment tools (including PREMM 5 ). Universal screening programs for LS should include both CRC and EC. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Annonacin Exerts Antitumor Activity through Induction of Apoptosis and Extracellular Signal-regulated Kinase Inhibition

PubMed Central

Yap, Chee Voon; Subramaniam, Kavita S.; Khor, Sik Wey; Chung, Ivy

2017-01-01

Background: Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries. Annonacin, a natural pure compound extracted from the seeds of Annona muricata, is a potential alternative therapeutic agent to treat EC. Objective: To study the antitumor activity of annonacin and its mechanism of action in EC cells (ECCs). Materials and Methods: Viability of ECCs treated with annonacin for 72 h was determined using methyl thiazolyl tetrazolium assay. The induction of cell cycle arrest and apoptotic cell death was evaluated using propidium iodide and annexin V-PE/7-AAD assay, respectively. DNA strand breaks were visualized using transferase dUTP nick end labeling assay, and the effects of annonacin on survival signaling were determined using western blotting. Results: Annonacin exhibited antiproliferative effects on EC cell lines (ECC-1 and HEC-1A) and primary cells (EC6-ept and EC14-ept) with EC50values ranging from 4.62 to 4.92 μg/ml. EC cells were shown arrested at G2/M phase after treated with 4 μg/ml of annonacin for 72 h. This led to a significant increase in apoptotic cell death (65.7%) in these cells when compared to vehicle-treated cells (P < 0.005). We further showed that annonacin-mediated apoptotic cell death was associated with an increase in caspase-3 cleavage and DNA fragmentation. Cell apoptosis was accompanied with downregulation of extracellular signal-regulated kinase survival protein expression and induction of G2/M cell cycle arrest. Conclusion: Annonacin may be a potential novel therapeutic agent for EC patients. SUMMARY We aimed to study the antitumor activity of annonacin and its mechanism of action in endometrial cancer cells. Annonacin exerted antiproliferation effects on both endometrial cancer cell lines and primary cells via induction of apoptosis and inhibition of extracellular signal-regulated kinase. Our data represented that annonacin could be an alternative therapeutic treatment to combat endometrial cancer. Abbreviations Used: 7-AAD: 7-Amino-Actinomycin, ATP: Adenosine diphosphate, BSA: Bovine serum albumin, DNA: Deoxyribonucleic acid, EC: Endometrial cancer, ECC-1: Endometrial cancer cell-1, EC50: Half maximal effective concentration, Ept: Epithelial, FBS: Fetal bovine serum, HEC-1A: Human endometrial carcinoma-1A, MTT: Methyl thiazolyl tetrazolium, NaCl: Sodium chloride, NADH: Nicotinamide adenine dinucleotide, RPMI 1640: Roswell Park Memorial Institute Medium, SDS: Sodium dodecyl sulfate PMID:29263632

The effects of the insecticide lambda-Cyhalothrin on the earthworm Eisenia fetida under experimental conditions of tropical and temperate regions.

PubMed

Garcia, Marcos; Scheffczyk, Adam; Garcia, Terezinha; Römbke, Jörg

2011-02-01

Plant Protection Products can affect soil organisms and thus might have negative impacts on soil functions. Little research has been performed on their impact on tropical soils. Therefore, the effects of the insecticide lambda-Cyhalothrin on earthworms were evaluated in acute and chronic laboratory tests modified for tropical conditions, i.e. at selected temperatures (20 and 28°C) and with two strains (temperate and tropical) of the compost worm Eisenia fetida. The insecticide was spiked in two natural soils, in OECD artificial soil and a newly developed tropical artificial soil. The effects of lambda-Cyhalothrin did rarely vary in the same soil at tropical (LC50: 68.5-229 mg a.i./kg dry weight (DW); EC50: 54.2-60.2 mg a.i./kg DW) and temperate (LC50: 99.8-140 mg a.i./kg DW; EC50: 37.4-44.5 mg a.i./kg DW) temperatures. In tests with tropical soils and high temperature, effect values differed by up to a factor of ten. Copyright © 2010 Elsevier Ltd. All rights reserved.

Low-Toxicity Diindol-3-ylmethanes as Potent Antifouling Compounds.

PubMed

Wang, Kai-Ling; Xu, Ying; Lu, Liang; Li, Yongxin; Han, Zhuang; Zhang, Jun; Shao, Chang-Lun; Wang, Chang-Yun; Qian, Pei-Yuan

2015-10-01

In the present study, eight natural products that belonged to di(1H-indol-3-yl)methane (DIM) family were isolated from Pseudovibrio denitrificans UST4-50 and tested for their antifouling activity against larval settlement (including both attachment and metamorphosis) of the barnacle Balanus (=Amphibalanus) amphitrite and the bryozoan Bugula neritina. All diindol-3-ylmethanes (DIMs) showed moderate to strong inhibitory effects against larval settlement of B. amphitrite with EC50 values ranging from 18.57 to 1.86 μM and could be considered as low-toxicity antifouling compounds since their LC50/EC50 ratios were larger than 15. Furthermore, the DIM- and 4-(di(1H-indol-3-yl)methyl)phenol (DIM-Ph-4-OH)-treated larvae completed normal settlement when they were transferred to clean seawater after being exposed to those compounds for 24 h. DIM also showed comparable antifouling performance to the commercial antifouling biocide Sea-Nine 211(™) in the field test over a period of 5 months, which further confirmed that DIMs can be considered as promising candidates of environmentally friendly antifouling compounds.

Effect of exposure routes on the relationships of lethal toxicity to rats from oral, intravenous, intraperitoneal and intramuscular routes.

PubMed

Ning, Zhong H; Long, Shuang; Zhou, Yuan Y; Peng, Zi Y; Sun, Yi N; Chen, Si W; Su, Li M; Zhao, Yuan H

2015-11-01

The lethal toxicity values (log 1/LD(50)) of 527 aliphatic and aromatic compounds in oral, intravenous, intramuscular and intraperitoneal routes were used to investigate the relationships of log 1/LD(50) from different exposure routes. Regression analysis shows that the log 1/LD(50) values are well correlated between intravenous and intraperitoneal or intramuscular injections. However, the correlations between oral and intravenous or intraperitoneal routes are relatively poor. Comparison of the average residuals indicates that intravenous injection is the most sensitive exposure route and oral administration is the least sensitive exposure route. This is attributed to the difference in kinetic process of toxicity testing. The toxic effect of a chemical can be similar or significantly different between exposure routes, depending on the absorption rates of chemicals into blood. Inclusion of hydrophobic parameter and fractions of ionic forms can improve the correlations between intravenous and intraperitoneal or oral routes, but not between intraperitoneal and oral routes. This is due to the differences of absorption rate in different exposure environments from different routes. Several factors, such as experimental uncertainty, metabolism and toxic kinetics, can affect the correlations between intravenous and intraperitoneal or oral routes. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of soil solution speciation and diffusive gradients in thin-films measurement as an indicator of copper bioavailability to plants.

PubMed

Zhao, Fang-Jie; Rooney, Corinne P; Zhang, Hao; McGrath, Steve P

2006-03-01

The toxicity effect concentrations (10% effective concentration [EC10] and 50% effective concentration [EC50]) of total added Cu derived from barley root elongation and tomato growth assays varied widely among 18 European soils. We investigated whether this variation could be explained by the solubility or speciation of Cu in soil solutions or the diffusive gradients in thin-films (DGT) measurement. Solubility and Cu speciation varied greatly among the soils tested. However, the EC10 and EC50 of soil solution Cu or free Cu2+ activity varied even more widely than those based on the total added Cu, indicating that solubility or soil solution speciation alone could not explain intersoil variation in Cu toxicity. Estimated EC10 and EC50 of free Cu2+ activity correlated closely and negatively with soil pH, indicating a protective effect of H+, which is consistent with the biotic ligand model concept. The DGT measurement was found to narrow the intersoil variation in EC50 considerably and to be a better predictor of plant Cu concentrations than either soil solution Cu or free Cu2+ activity. We conclude that plant bioavailability of Cu in soil depends on Cu speciation, interactions with protective ions (particularly H+), and the resupply from the solid phase, and we conclude that the DGT measurement provides a useful indicator of Cu bioavailability in soil.

Acute and chronic toxicity of aluminum to a unionid mussel (Lampsilis siliquoidea) and an amphipod (Hyalella azteca) in water‐only exposures

USGS Publications Warehouse

Wang, Ning; Ivey, Chris D.; Brunson, Eric L.; Cleveland, Danielle; Ingersoll, Christopher G.; Stubblefield, William A.; Cardwell, Allison S.

2018-01-01

The US Environmental Protection Agency (USEPA) is reviewing the protectiveness of the national ambient water quality criteria (WQC) for aluminum (Al) and compiling a toxicity data set to update the WQC. Freshwater mussels are one of the most imperiled groups of animals in the world, but little is known about their sensitivity to Al. The objective of the present study was to evaluate acute 96‐h and chronic 28‐d toxicity of Al to a unionid mussel (Lampsilis siliquoidea) and a commonly tested amphipod (Hyalella azteca) at a pH of 6 and water hardness of 100 mg/L as CaCO3. The acute 50% effect concentration (EC50) for survival of both species was >6200 μg total Al/L. The EC50 was greater than all acute values in the USEPA acute Al data set for freshwater species at a pH range of 5.0 to <6.5 and hardness normalized to 100 mg/L, indicating that the mussel and amphipod were insensitive to Al in acute exposures. The chronic 20% effect concentration (EC20) based on dry weight was 163 μg total Al/L for the mussel and 409 μg total Al/L for the amphipod. Addition of the EC20s to the USEPA chronic Al data set for pH 5.0 to <6.5 would rank the mussel (L. siliquoidea) as the fourth most sensitive species and the amphipod (H. azteca) as the fifth most sensitive species, indicating the 2 species were sensitive to Al in chronic exposures. The USEPA‐proposed acute and chronic WQC for Al would adequately protect the mussel and amphipod tested; however, inclusion of the chronic data from the present study and recalculation of the chronic criterion would likely lower the proposed chronic criterion. 

Design, synthesis, and anti-HIV-1 activity of 1-aromatic methyl-substituted 3-(3,5-dimethylbenzyl)uracil and N-3,5-dimethylbenzyl-substituted urea derivatives.

PubMed

Sakakibara, Norikazu; Baba, Masanori; Okamoto, Mika; Toyama, Masaaki; Demizu, Yosuke; Misawa, Takashi; Kurihara, Masaaki; Irie, Kohji; Kato, Yoshihisa; Maruyama, Tokumi

2015-02-01

A new series of 1-aromatic methyl-substituted 3-(3,5-dimethylbenzyl)uracil and N-3,5-dimethylbenzyl-substituted urea derivatives were synthesized and evaluated as non-nucleoside HIV-1 reverse transcriptase inhibitors. A series of new 6-azido and 6-amino derivatives of 1-substituted-3-(3,5-dimethylbenzyl)uracils were synthesized using our previously reported method, and three acyclic derivatives were synthesized from urea. The anti-HIV-1 activities of these compounds were determined based on the inhibition of virus-induced cytopathogenicity in MT-4 cells. The cytotoxicities of the compounds were evaluated using the viability of mock-infected cells. Some of these compounds showed good-to-moderate activities against HIV-1 with half maximal effective concentration (EC50) values in the submicromolar or subnanomolar range. Compared with emivirine, compound 6-amino-3-(3,5-dimethylbenzyl)-1-(4-aminobenzyl)uracil showed significant anti-HIV-1 activity with an EC50 value of 10 nM and a high selectivity index of 1923. Preliminary structure-activity relationship studies and molecular modeling analyses were carried out to explore the major interactions between HIV-1 reverse transcriptase and the potent inhibitor 6-amino-3-(3,5-dimethylbenzyl)-1-(4-aminobenzyl)uracil; these results may be important for further development of this class of compounds as anti-HIV-1 agents. The excellent activity of 6-amino-3-(3,5-dimethylbenzyl)-1-(4-aminobenzyl)uracil (EC50: 0.010 ± 0.006 µM, SI: >1923) may serve as the basis for conducting further investigations on the behavior of this class of compounds against drug-resistant mutants. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Design, synthesis, and anti-HIV-1 activity of 1-aromatic methyl-substituted 3-(3,5-dimethylbenzyl)uracil and N-3,5-dimethylbenzyl-substituted urea derivatives

PubMed Central

Sakakibara, Norikazu; Baba, Masanori; Okamoto, Mika; Toyama, Masaaki; Demizu, Yosuke; Misawa, Takashi; Kurihara, Masaaki; Irie, Kohji; Kato, Yoshihisa; Maruyama, Tokumi

2015-01-01

Background A new series of 1-aromatic methyl-substituted 3-(3,5-dimethylbenzyl)uracil and N-3,5-dimethylbenzyl-substituted urea derivatives were synthesized and evaluated as non-nucleoside HIV-1 reverse transcriptase inhibitors. Methods A series of new 6-azido and 6-amino derivatives of 1-substituted-3-(3,5-dimethylbenzyl)uracils were synthesized using our previously reported method, and three acyclic derivatives were synthesized from urea. The anti-HIV-1 activities of these compounds were determined based on the inhibition of virus-induced cytopathogenicity in MT-4 cells. The cytotoxicities of the compounds were evaluated using the viability of mock-infected cells. Results Some of these compounds showed good-to-moderate activities against HIV-1 with half maximal effective concentration (EC50) values in the submicromolar or subnanomolar range. Compared with emivirine, compound 6-amino-3-(3,5-dimethylbenzyl)-1-(4-aminobenzyl)uracil showed significant anti-HIV-1 activity with an EC50 value of 10 nM and a high selectivity index of 1923. Preliminary structure–activity relationship studies and molecular modeling analyses were carried out to explore the major interactions between HIV-1 reverse transcriptase and the potent inhibitor 6-amino-3-(3,5-dimethylbenzyl)-1-(4-aminobenzyl)uracil; these results may be important for further development of this class of compounds as anti-HIV-1 agents. Conclusion The excellent activity of 6-amino-3-(3,5-dimethylbenzyl)-1-(4-aminobenzyl)uracil (EC50: 0.010 ± 0.006 µM, SI: >1923) may serve as the basis for conducting further investigations on the behavior of this class of compounds against drug-resistant mutants. PMID:26149262

Experimental design and modelling approach to evaluate efficacy of β-lactam/β-lactamase inhibitor combinations.

PubMed

Sy, S K B; Derendorf, H

2017-07-29

A β-lactamase inhibitor (BLI) confers susceptibility of β-lactamase-expressing multidrug resistant (MDR) organisms to the partnering β-lactam (BL). To discuss the experimental design and modelling strategies for two-drug combinations, using ceftazidime- and aztreonam-avibactam combinations, as examples. The information came from several publications on avibactam in vitro time-kill studies and corresponding pharmacodynamic models. The experimental design to optimally gather crucial information from constant-concentration time-kill studies is to use an agile matrix of two-drug concentration combinations that cover 0.25- to 4-fold BL minimum inhibitory concentration (MIC) relative to the BLI concentrations to be tested against the particular isolate. This shifting agile design can save substantial costs and resources, without sacrificing crucial information needed for model development. The complex synergistic BL/BLI interaction is quantitatively explored using a semi-mechanistic pharmacokinetic-pharmacodynamic (PK/PD) mathematical model that accounts for antimicrobial activities in the combination, bacteria-mediated BL degradation and inhibition of BL degradation by BLI. A predictive mathematical formulation for the two-drug killing effects preserves the correlation between the model-derived EC 50 of BL and the BL MIC. The predictive value of PK/PD model is evaluated against external data that were not used for model development, including but not limited to in vitro hollow fibre and in vivo murine infection models. As a framework for translational predictions, the goal of this modelling strategy is to significantly decrease the decision-making time by running clinical trial simulations with MIC-substituted EC 50 function for isolates of comparable susceptibility through established correlation between BL MIC and EC 50 values. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Two opposite dose-dependent effects of diazinon on the motor activity of the rat ileum.

PubMed

Trailović, Saša M; Marjanović, Djordje S; Uzelac, Teodora Vidonja; Milovanović, Mirjana; Trailović, Jelena Nedeljković

2017-06-01

Acute poisoning with OPs may lead to a range of neurological effects, which cannot be explained by AChE inhibition alone. Several OPs interact directly with cholinergic receptors in mammals, but such data does not exist for invertebrates. The aim of current study was to investigate the direct and indirect effects of diazinon on the contractions of rat ileum and to compare those effects on the nervemuscle preparation of the Ascaris suum. In the presence of increasing concentrations of diazinon (3, 10 and 30nM), EFS-induced ileal contractions were increased significantly. In the same preparation, diazinon 3nM, significantly increased contractions induced by EFS, but did not affect the contractions caused by 5MFI. Contrarily, 1μM of diazinon significantly and reversibly inhibited the EFS-induced ileal contractions. Diazinon exhibited competitive and non-competitive inhibitions of 5MFI induced contractions. The control EC 50 of 5MFI was 2.48μM with R max =1.88g. In the presence of diazinon, EC 50 was 12.45μM, while R max was reduced to 0.43g. After washing, the EC 50 and R max values were again closer to the control level (3.80μM and 1.04g). Diazinon 1μM did not inhibit Ascaris suum contractions caused by ACh, but it increased the R max . Diazinon in our study exhibits two opposite effects on the motor activity of the ileum. In low nanomolar concentrations the dominat is its effect on AChE and the stimulation of contractions. Furthermore, in concentrations that approach micromolar values diazinon has a direct inhibitory effect on muscarinic receptors. The direct inhibitory effect of diazinon on A. suum contractions was not found. Copyright © 2017 Elsevier Ltd. All rights reserved.

Developmental toxicity, acute toxicity and mutagenicity testing in freshwater snails Biomphalaria glabrata (Mollusca: Gastropoda) exposed to chromium and water samples.

PubMed

Tallarico, Lenita de Freitas; Borrely, Sueli Ivone; Hamada, Natália; Grazeffe, Vanessa Siqueira; Ohlweiler, Fernanda Pires; Okazaki, Kayo; Granatelli, Amanda Tosatte; Pereira, Ivana Wuo; Pereira, Carlos Alberto de Bragança; Nakano, Eliana

2014-12-01

A protocol combining acute toxicity, developmental toxicity and mutagenicity analysis in freshwater snail Biomphalaria glabrata for application in ecotoxicological studies is described. For acute toxicity testing, LC50 and EC50 values were determined; dominant lethal mutations induction was the endpoint for mutagenicity analysis. Reference toxicant potassium dichromate (K2Cr2O7) was used to characterize B. glabrata sensitivity for toxicity and cyclophosphamide to mutagenicity testing purposes. Compared to other relevant freshwater species, B. glabrata showed high sensitivity: the lowest EC50 value was obtained with embryos at veliger stage (5.76mg/L). To assess the model applicability for environmental studies, influent and effluent water samples from a wastewater treatment plant were evaluated. Gastropod sensitivity was assessed in comparison to the standardized bioassay with Daphnia similis exposed to the same water samples. Sampling sites identified as toxic to daphnids were also detected by snails, showing a qualitatively similar sensitivity suggesting that B. glabrata is a suitable test species for freshwater monitoring. Holding procedures and protocols implemented for toxicity and developmental bioassays showed to be in compliance with international standards for intra-laboratory precision. Thereby, we are proposing this system for application in ecotoxicological studies. Copyright © 2014 Elsevier Inc. All rights reserved.

Antitumor and antiviral activity of Colombian medicinal plant extracts.

PubMed

Betancur-Galvis, L; Saez, J; Granados, H; Salazar, A; Ossa, J

1999-01-01

Extracts of nine species of plants traditionally used in Colombia for the treatment of a variety of diseases were tested in vitro for their potential antitumor (cytotoxicity) and antiherpetic activity. MTT (Tetrazolium blue) and Neutral Red colorimetric assays were used to evaluate the reduction of viability of cell cultures in presence and absence of the extracts. MTT was also used to evaluate the effects of the extracts on the lytic activity of herpes simplex virus type 2 (HSV-2). The 50% cytotoxic concentration (CC50) and the 50% inhibitory concentration of the viral effect (EC50) for each extract were calculated by linear regression analysis. Extracts from Annona muricata, A. cherimolia and Rollinia membranacea, known for their cytotoxicity were used as positive controls. Likewise, acyclovir and heparin were used as positive controls of antiherpetic activity. Methanolic extract from Annona sp. on HEp-2 cells presented a CC50 value at 72 hr of 49.6x10(3)mg/ml. Neither of the other extracts examined showed a significant cytotoxicity. The aqueous extract from Beta vulgaris, the ethanol extract from Callisia grasilis and the methanol extract Annona sp. showed some antiherpetic activity with acceptable therapeutic indexes (the ratio of CC50 to EC50). These species are good candidates for further activity-monitored fractionation to identify active principles.

Cytotoxic activity of a methanol extract of Phallusia nigra (Tunicata, Ascidiacea).

PubMed

Costa, L V; Malpezzi, E L; Matsui, D H; Machado-Santelli, G M; Freitas, J C

1996-03-01

Tunicates have been reported to be a rich source of biologically active compounds. In this study, we demonstrate the presence of cytotoxic substances in Phallusia nigra, a common tunicate from Brazilian coastal waters. An extract of tunicate tissue was obtained by homogenizing the visceral organs from 50 specimens in methanol, followed by filtration and concentration in a rotary vacuum evaporator. Finally, the concentrate was partitioned with chloroform to remove lipids. The resulting extract possessed antimitotic and hemolytic activity. The former was demonstrated as a delay in the development of sea urchin eggs by partially inhibiting the process of cleavage (first cleavage, EC50 +/- SEM = 3.44 +/- 0.84 mg/ml). The < 500 molecular fraction of the extract obtained by ultrafiltration also inhibited cell proliferation (the number of viable cells was decreased by 68% with 500 micrograms/ml) and DNA synthesis of T47D cells derived from human breast carcinoma as measured by [3H]-thymidine incorporation (66% of the control value after 24-h incubation with 100 micrograms/ml). Dose-dependent hemolysis obtained with P. nigra extract on mouse erythrocytes had an EC50 +/- SEM = 1.12 +/- 0.02 mg/ml for a 0.5% erythrocyte suspension. Hemolysis could be reduced by pre-incubating the cells with choline-containing phospholipid. Sphingomyelin (40 micrograms/ml) increased the EC50 by two-fold to 2.86 +/- 0.04 mg/ml, but phosphatidylcholine (80 micrograms/ml) did not modify hemolysis.

Leishmanicidal activity of an alkenylphenol from Piper malacophyllum is related to plasma membrane disruption.

PubMed

de Oliveira, Alberto; Mesquita, Juliana T; Tempone, André G; Lago, João Henrique G; Guimarães, Elsie F; Kato, Massuo J

2012-11-01

Leishmaniasis and Chagas disease are parasitic protozoan infections that affect the poorest population in the world, causing high mortality and morbidity. As a result of highly toxic and long-duration treatments, novel, safe and more efficacious drugs are essential. In this work, the methanol (MeOH) extract from the leaves of Piper malacophyllum (Piperaceae) was fractioned to afford one alkenylphenol, which was characterized as 4-[(3'E)-decenyl]phenol (gibbilimbol B) by spectroscopic methods. Anti-protozoan in vitro assays demonstrated for the first time that Leishmania (L.) infantum chagasi was susceptible to gibbilimbol B, with an in vitro EC(50) of 23 μg/mL against axenic promastigotes and an EC(50) of 22 μg/mL against intracellular amastigotes. Gibbilimbol B was also tested for anti-trypanosomal activity (Trypanosoma cruzi) and showed an EC(50) value of 17 μg/mL against trypomastigotes. To evaluate the cytotoxic parameters, this alkenylphenol was tested in vitro against NCTC cells, showing a CC(50) of 59 μg/mL and absent hemolytic activity at the highest concentration of 75 μg/mL. Using the fluorescent probe SYTOX Green suggested that the alkenylphenol disrupted the Leishmania plasma membrane upon initial incubation. Further drug design studies aiming at derivatives could be a promising tool for the development of new therapeutic agents for leishmaniasis and Chagas disease. Copyright © 2012 Elsevier Inc. All rights reserved.

Discovery and structure-activity relationships of (2-(arylthio)benzylideneamino)guanidines as a novel series of potent apoptosis inducers.

PubMed

Zhang, Han-Zhong; Crogan-Grundy, Candace; May, Chris; Drewe, John; Tseng, Ben; Cai, Sui Xiong

2009-04-01

1-(2-(2,5-Dimethoxyphenylthio)benzylidene)semicarbazide (2a) was discovered as a potent apoptosis inducer through our cell based HTS assay. SAR study led to the discovery of a more aqueous soluble analog (2-(2,5-dimethoxyphenylthio)-6-methoxybenzylideneamino)guanidine (5e) with EC(50) value of 60 nM in the caspase activation assay and GI(50) value of 62 nM in the growth inhibition assay in T47D cells. Compound 5e was found to be an inhibitor of tubulin polymerization and efficacious in a MX-1 breast tumor model.

Multi-objective optimization integrated with life cycle assessment for rainwater harvesting systems

NASA Astrophysics Data System (ADS)

Li, Yi; Huang, Youyi; Ye, Quanliang; Zhang, Wenlong; Meng, Fangang; Zhang, Shanxue

2018-03-01

The major limitation of optimization models applied previously for rainwater harvesting (RWH) systems is the systematic evaluation of environmental and human health impacts across all the lifecycle stages. This study integrated life cycle assessment (LCA) into a multi-objective optimization model to optimize the construction areas of green rooftops, porous pavements and green lands in Beijing of China, considering the trade-offs among 24 h-interval RWH volume (QR), stormwater runoff volume control ratio (R), economic cost (EC), and environmental impacts (EI). Eleven life cycle impact indicators were assessed with a functional unit of 10,000 m2 of RWH construction areas. The LCA results showed that green lands performed the smallest lifecycle impacts of all assessment indicators, in contrast, porous pavements showed the largest impact values except Abiotic Depletion Potential (ADP) elements. Based on the standardization results, ADP fossil was chosen as the representative indicator for the calculation of EI objective in multi-objective optimization model due to its largest value in all RWH systems lifecycle. The optimization results for QR, R, EC and EI were 238.80 million m3, 78.5%, 66.68 billion RMB Yuan, and 1.05E + 16 MJ, respectively. After the construction of optimal RWH system, 14.7% of annual domestic water consumption and 78.5% of maximum daily rainfall would be supplied and controlled in Beijing, respectively, which would make a great contribution to reduce the stress of water scarcity and water logging problems. Green lands have been the first choice for RWH in Beijing according to the capacity of rainwater harvesting and less environmental and human impacts. Porous pavements played a good role in water logging alleviation (R for 67.5%), however, did not show a large construction result in this study due to the huge ADP fossil across the lifecycle. Sensitivity analysis revealed the daily maximum precipitation to be key factor for the robustness of the results for three RWH systems construction in this study.

Synthesis, molecular modeling studies and biological evaluation of fluorine substituted analogs of GW 501516.

PubMed

Ciocoiu, Calin C; Ravna, Aina W; Sylte, Ingebrigt; Rustan, Arild C; Hansen, Trond Vidar

2011-12-01

(±)-2-Fluoro-2-(2-methyl-4-(((4-methyl-2-(4-(trifluoromethyl)phenyl)thiazol-5-yl)methyl)thio)phenoxy)acetic acid (2a) has been prepared and subjected to biological testing against all three subtypes of the PPARs. This compound exhibited agonist effects with EC(50) values of 560 and 55 nM against PPARα and PPARδ, respectively, in a luciferase assay. Moreover, compound (±)-2a also exhibited potent ability to induce oleic acid oxidation in a human myotube cell assay with EC(50)=3.7 nM. Compound (±)-2a can be classified as a dual PPARα/δ agonist with a 10-fold higher potency against the PPARδ receptor than against the PPARα receptor. Molecular modeling studies revealed that both enantiomers of 2a bind to the PPARδ receptor with similar binding energies. Copyright © 2011 Elsevier Ltd. All rights reserved.

Sensitivity of early life stages of freshwater mussels (Unionidae) to acute and chronic toxicity of lead, cadmium, and zinc in water

USGS Publications Warehouse

Wang, N.; Ingersoll, C.G.; Ivey, C.D.; Hardesty, D.K.; May, T.W.; Augspurger, T.; Roberts, A.D.; Van Genderen, E.; Barnhart, M.C.

2010-01-01

Toxicity of lead, cadmium, or zinc to early life stages of freshwater mussels (fatmucket, Lampsilis siliquoidea; Neosho mucket, L. rafinesqueana) was evaluated in 48-h exposures with mussel larvae (glochidia), in 96-h exposures with newly transformed (5-d-old) and two- or six-month-old juvenile mussels, or in 28-d exposures with two- or four-month-old mussels in reconstituted soft water. The 24-h median effect concentrations (EC50s) for fatmucket glochidia (>299??g Pb/L, >227??g Cd/L, 2,685??g Zn/L) and 96-h EC50s for two- or six-month-old fatmucket (>426??g Pb/L, 199??g Cd/L, 1,700??g Zn/L) were much higher than 96-h EC50s for newly transformed fatmucket (142 and 298??g Pb/L, 16??g Cd/L, 151 and 175??g Zn/L) and Neosho mucket (188??g Pb/L, 20??g Cd/L, 145??g Zn/L). Chronic values for fatmucket were 10??g Pb/L, 6.0??g Cd/L, and 63 and 68??g Zn/L. When mussel data from the present study and the literature were included in updated databases for deriving U.S. Environmental Protection Agency water quality criteria, mussel genus mean acute values were in the lower percentiles of the sensitivity distribution of all freshwater species for Pb (the 26th percentile), Cd (the 15th to 29th percentile), or Zn (the 12th to 21st percentile). The mussel (Lampsilis) genus mean chronic value was the lowest value ever reported for Pb (the 9th percentile) but was near the middle of the sensitivity distribution for Cd (the 61st percentile) or Zn (the 44th percentile). These results indicate that mussels were relatively sensitive to the acute toxicity of these three metals and to the chronic toxicity of Pb, but were moderately sensitive to the chronic toxicity of Cd or Zn compared to other freshwater species. ?? 2010 SETAC.

Sensitivity of early life stages of freshwater mussels (Unionidae) to acute and chronic toxicity of lead, cadmium, and zinc in water.

PubMed

Wang, Ning; Ingersoll, Christopher G; Ivey, Christopher D; Hardesty, Douglas K; May, Thomas W; Augspurger, Tom; Roberts, Andy D; van Genderen, Eric; Barnhart, M Chris

2010-09-01

Toxicity of lead, cadmium, or zinc to early life stages of freshwater mussels (fatmucket, Lampsilis siliquoidea; Neosho mucket, L. rafinesqueana) was evaluated in 48-h exposures with mussel larvae (glochidia), in 96-h exposures with newly transformed (5-d-old) and two- or six-month-old juvenile mussels, or in 28-d exposures with two- or four-month-old mussels in reconstituted soft water. The 24-h median effect concentrations (EC50s) for fatmucket glochidia (>299 microg Pb/L, >227 microg Cd/L, 2,685 microg Zn/L) and 96-h EC50s for two- or six-month-old fatmucket (>426 microg Pb/L, 199 microg Cd/L, 1,700 microg Zn/L) were much higher than 96-h EC50s for newly transformed fatmucket (142 and 298 microg Pb/L, 16 microg Cd/L, 151 and 175 microg Zn/L) and Neosho mucket (188 microg Pb/L, 20 microg Cd/L, 145 microg Zn/L). Chronic values for fatmucket were 10 microg Pb/L, 6.0 microg Cd/L, and 63 and 68 microg Zn/L. When mussel data from the present study and the literature were included in updated databases for deriving U.S. Environmental Protection Agency water quality criteria, mussel genus mean acute values were in the lower percentiles of the sensitivity distribution of all freshwater species for Pb (the 26th percentile), Cd (the 15th to 29th percentile), or Zn (the 12th to 21st percentile). The mussel (Lampsilis) genus mean chronic value was the lowest value ever reported for Pb (the 9th percentile) but was near the middle of the sensitivity distribution for Cd (the 61st percentile) or Zn (the 44th percentile). These results indicate that mussels were relatively sensitive to the acute toxicity of these three metals and to the chronic toxicity of Pb, but were moderately sensitive to the chronic toxicity of Cd or Zn compared to other freshwater species. Copyright 2010 SETAC.

In vitro activity of tafenoquine alone and in combination with artemisinin against Plasmodium falciparum.

PubMed

Ramharter, Michael; Noedl, Harald; Thimasarn, Krongthong; Wiedermann, Gerhard; Wernsdorfer, Gunther; Wernsdorfer, Walther H

2002-07-01

Emergence and spread of drug-resistant falciparum malaria has created an urgent demand for alternative therapeutic agents. This study was conducted to assess the in vitro blood schizontocidal activity of tafenoquine, the most advanced candidate drug of the 8-aminoquinolines, and of its 1:1 combination with artemisinin in fresh isolates of Plasmodium falciparum in an area with multi-drug resistance, measuring the inhibition of schizont maturation. In 43 successfully tested parasite isolates, the mean effective concentrations (ECs) of tafenoquine were 209 nmol/L for the EC50, and 1,414 nmol/L for the EC90. Tafenoquine showed no significant activity relationships with mefloquine, artemisinin, and chloroquine. With quinine, a highly significant activity relationship was observed at the EC50, but not at the EC90. The EC50, and EC90 of the tafenoquine-artemisinin combination were 15.9 nmol/L and 84.3 nmol/L. The combination was synergistic. Tafenoquine appears to be a promising candidate for treating multidrug-resistant falciparum malaria, especially in combination with artemisinin derivatives.

The Plant Alkaloid Camptothecin as a Novel Antifouling Compound for Marine Paints: Laboratory Bioassays and Field Trials.

PubMed

Feng, Dan Qing; He, Jian; Chen, Si Yu; Su, Pei; Ke, Cai Huan; Wang, Wei

2018-06-02

The extensive use of copper and booster biocides in antifouling (AF) paints has raised environmental concerns and the need to develop new AF agents. In the present study, 18 alkaloids derived from terrestrial plants were initially evaluated for AF activity using laboratory bioassays with the bryozoan Bugula neritina and the barnacle Balanus albicostatus. The results showed that 4 of the 18 alkaloids were effective in inhibiting larval settlement of B. neritina, with an EC 50 range of 6.18 to 43.11 μM, and 15 of the 18 alkaloids inhibited larval settlement of B. albicostatus, with EC 50 values ranging from 1.18 to 67.58 μM. Field trials that incorporated five alkaloids respectively into paints with 20% w/w indicated an in situ AF efficiency of evodiamine, strychnine, camptothecin (CPT), and cepharanthine, with the most potent compound being CPT, which also exhibited stronger AF efficiency than the commercial antifoulants cuprous oxide and zinc pyrithione in the field over a period of 12 months. Further field trials with different CPT concentrations (0.1 to 20% w/w) in the paints suggested a concentration-dependent AF performance in the natural environment, and the effective concentrations to significantly inhibit settlement of biofoulers in the field were ≥ 0.5% w/w (the efficiency of 0.5% w/w lasted for 2 months). Moreover, CPT toxicity against the crustacean Artemia salina, the planktonic microalgae Phaeodactylum tricornutum and Isochrysis galbana, was examined. The results showed that 24 h LC 50 of CPT against A. salina was 20.75 μM, and 96 h EC 50 (growth inhibition) values of CPT to P. tricornutum and I. galbana were 55.81 and 6.29 μM, respectively, indicating that CPT was comparatively less toxic than several commercial antifoulants previously reported. Our results suggest the novel potential application of CPT as an antifoulant.

Pharmacological characterization of the bifunctional opioid ligand H-Dmt-Tic-Gly-NH-Bzl (UFP-505).

PubMed

Dietis, N; McDonald, J; Molinari, S; Calo, G; Guerrini, R; Rowbotham, D J; Lambert, D G

2012-02-01

While producing good-quality analgesia, µ-opioid (MOP) receptor activation produces a number of side-effects including tolerance. Simultaneous blockade of δ-opioid (DOP) receptors has been shown to reduce tolerance to morphine. Here, we characterize a prototype bifunctional opioid H-Dmt-Tic-Gly-NH-Bzl (UFP-505). We measured receptor binding affinity in Chinese hamster ovary (CHO) cells expressing recombinant human MOP, DOP, k-opioid (KOP), nociceptin/orphanin (NOP) receptors. For activation, we measured the binding of GTPγ(35)S to membranes from CHO(hMOP), CHO(hDOP), rat cerebrocortex, and rat spinal cord. In addition, we assessed 'end organ' responses in the guinea pig ileum and mouse vas deferens. UFP-505 bound to CHO(hMOP) and CHO(hDOP) with (binding affinity) pK(i) values of 7.79 and 9.82, respectively. There was a weak interaction at KOP and NOP (pK(i) 6.29 and 5.86). At CHO(hMOP), UFP-505 stimulated GTPγ(35)S binding with potency (pEC(50)) of 6.37 and in CHO(hDOP) reversed the effects of a DOP agonist with affinity (pK(b)) of 9.81 (in agreement with pK(i) at DOP). UFP-505 also stimulated GTPγ(35)S binding in rat cerebrocortex and spinal cord with pEC(50) values of 6.11-6.53. In the guinea pig ileum (MOP-rich preparation), UFP-505 inhibited contractility with pEC(50) of 7.50 and in the vas deferens (DOP-rich preparation) reversed the effects of a DOP agonist with an affinity (pA(2)) of 9.15. We have shown in a range of preparations and assays that UFP-505 behaves as a potent MOP agonist and DOP antagonist; a MOP/DOP bifunctional opioid. Further studies in dual expression systems and whole animals with this prototype are warranted.

Effect of beta-ADrenergic Agonist on Cyclic AMP Synthesis in Chicken Skeletal Muscle Cells in Culture

NASA Technical Reports Server (NTRS)

Young, R. B.; Bridge, K. Y.; Rose, M. Franklin (Technical Monitor)

2000-01-01

Several beta-adrenergic receptor (bAR) agonists are known to cause hypertrophy of skeletal muscle tissue. Because it seems logical that these agonists exert their action on muscle through stimulation of cAMP synthesis, five bAR agonists encompassing a range in activity from strong to weak were evaluated for their ability to stimulate cAMP accumulation in embryonic chicken skeletal muscle cells in culture. Two strong agonists (epinephrine and isoproterenol), one moderate agonist (albuterol), and two weak agonists known to cause hypertrophy in animals (clenbuterol and cimaterol) were studied. Dose response curves were determined over six orders of magnitude in concentration for each agonist, and values were determined for their maximum stimulation of cAMP synthesis rate (Bmax) and the agonist concentration at which 50% stimulation of cAMP synthesis (EC50) occurred. Bmax values decreased in the following order: isoproterenol, epinephrine, albuterol, cimaterol, clenbuterol. Cimaterol and clenbuterol at their Bmax levels were approximately 15-fold weaker than isoproterenol in stimulating the rate of cAMP synthesis. In addition, the EC50 values for isoproterenol, cimaterol, clenbuterol, epinephrine, and albuterol were 360 nM, 630 nM, 900 nM, 2,470 nM, and 3,650 nM, respectively. Finally, dose response curves show that the concentrations of cimaterol and clenbuterol in culture media at concentrations known to cause significant muscle hypertrophy in animals had no detectable effect on stimulation of CAMP accumulation in chicken skeletal muscle cells.

Evaluation of entropy for monitoring the depth of anesthesia compared with bispectral index: a multicenter clinical trial.

PubMed

Gao, Jian-dong; Zhao, Yu-jie; Xu, Chen-shi; Zhao, Jing; Huang, Yu-guang; Wang, Tian-long; Pei, Ling; Wang, Jian; Yao, Li-nong; Ding, Qian; Tan, Zhi-ming; Zhu, Zhi-rong; Yue, Yun

2012-04-01

As a new electroencephalogram (EEG) signal processing technique for monitoring the depth of anesthesia, entropy consists of two indices: reaction entropy (RE) and state entropy (SE). Our study compared entropy with classical bispectral index (BIS) in reduction of myoelectrical interference and noxious stimuli with EEG signals. Two hundred and eighty patients (ASA I-II, 18-60 years old) undergoing scheduled surgeries from seven medical centers were enrolled. Anesthesia induction was managed with propofol via the target-controlled infusion (TCI) system. The results of BIS, RE, SE, mean arterial pressure (MAP) and heart rate (HR) were recorded before anesthesia induction, at the moment of unconsciousness, before and 2 minutes after administration of muscle relaxant, and before and one and three minutes after the tracheal intubation. The values of half maximum effective concentrations (EC50), 5% effective concentrations (EC05) and 95% effective concentrations (EC95) of propofol effect-site concentration at the onset of unconsciousness were 1.2 (1.1-1.3 µg/ml), 2.5 (2.4-2.5 µg/ml) and 3.7 (3.7-3.8 µg/ml), while those of the predicted plasma propofol concentration were 2.8 (2.7-2.9 µg/ml), 3.9 (3.8-3.9 µg/ml) and 4.9 (4.8-5.0 µg/ml), respectively. The values of BIS, SE and RE were 62, 59 and 63 when 50% of patients lost consciousness, and 79, 80, 85 and 42, 37, 44, respectively, when 5% and 95% of patients were unconscious. The values of BIS, RE and SE dropped two minutes after the injection of muscle relaxant, but there were no significant differences between RE and SE. MAP and HR increased visibly, which indicated a reaction to tracheal intubation; the values of BIS, RE and SE, however, did not display any significant changes. This large-sample multicentric study confirmed the values of RE and SE as approximating BIS value, at the onset of unconsciousness during propofol TCI anesthesia. After elimination of myoelectrical activation, all values of RE, SE and BIS decreased significantly and the three indices were less sensitive to noxious stimuli than cardiovascular responses.

Effects of lipopolysaccharide from Pseudomonas aeruginosa on airway smooth muscle functions in guinea pigs.

PubMed

Yamawaki, I; Tamaoki, J; Kanemura, T; Horii, S; Takizawa, T

1990-01-01

To elucidate the mechanisms of airway hyperreactivity induced by lipopolysaccharide (LPS), we studied isolated tracheal segments from guinea pigs under isometric conditions in vitro. Guinea pigs were injected intraperitoneally with endotoxin (1 mg/kg; LPS from Pseudomonas aeruginosa, serotype 10) for 4 days, and animals treated with sterile nonpyrogenic saline served as controls. Histological examination of trachea revealed moderate structural damage of epithelial layer in the LPS-treated group. Treatment with LPS potentiated the contractile responses of tracheal smooth muscle to acetylcholine, causing a leftward displacement of dose-response curves so that the EC50 values decreased from 1.1 +/- 3.7 x 10(-5) to 4.4 +/- 3.7 x 10(-7) M (mean +/- SE, p less than 0.01). Likewise, LPS shifted the dose-response curves for histamine and substance P to lower concentrations by approximately 0.5-1.0 log U. Each of these potentiations was not affected by pretreatment of tissues with indomethacin or propranolol. Addition of isoproterenol to tracheal segments precontracted with acetylcholine caused concentration-dependent relaxation, an effect that was significantly greater in controls than in the LPS-treated group. These results suggest that airway hyperreactivity induced by LPS in guinea pigs may be attributed to a decreased ability of respiratory epithelial cells to generate a relaxing factor.

Active Wireline Heave Compensation for Ocean Drilling

NASA Astrophysics Data System (ADS)

Goldberg, D.; Liu, T.; Swain, K.; Furman, C.; Iturrino, G. J.

2014-12-01

The up-and-down heave motion of a ship causes a similar motion on any instruments tethered on wireline cable below it. If the amplitude of this motion is greater than a few tens of cm, significant discrepancy in the depth below the ship is introduced, causing uncertainty in the acquired data. Large and irregular cabled motions also increase the risk of damaging tethered instruments, particularly those with relatively delicate sensors. In 2005, Schlumberger and Deep Down, Inc built an active wireline heave compensator (AHC) system for use onboard the JOIDES Resolution to compensate for heave motion on wireline logging tools deployed in scientific drill holes. The goals for the new AHC system were to (1) design a reliable heave compensation system; and (2) devise a robust and quantitative methodology for routine assessment of compensation efficiency (CE) during wireline operations. Software programs were developed to monitor CE and the dynamics of logging tools in real-time, including system performance under variable parameters such as water depth, sea state, cable length, logging speed and direction. We present the CE results from the AHC system on the JOIDES Resolution during a 5-year period of recent IODP operations and compare the results to those from previous compensation systems deployed during ODP and IODP. Based on new data under heave conditions of ±0.2-2.0 m and water depths of 300-4,800 m in open holes, the system reduces 65-80% of downhole tool displacement under stationary conditions and 50-60% during normal logging operations. Moreover, down/up tool motion at low speeds (300-600 m/h) reduces the system's CE values by 15-20%, and logging down at higher speeds (1,000-1,200 m/h) reduces CE values by 55-65%. Furthermore, the system yields slightly lower CE values of 40-50% without tension feedback of the downhole cable while logging. These results indicate that the new system's compensation efficiency is comparable to or better than previous systems, with additional advantages that include upgradable compensation control software and the capability for continued assessment under varying environmental conditions. Future integration of downhole cable dynamics as an input feedback could further improve CE during logging operations.­

Unraveling the cytotoxicity and metabolic pathways of binary natural deep eutectic solvent systems

PubMed Central

Mbous, Yves Paul; Hayyan, Maan; Wong, Won Fen; Looi, Chung Yeng; Hashim, Mohd Ali

2017-01-01

In this study, the anticancer potential and cytotoxicity of natural deep eutectic solvents (NADESs) were assessed using HelaS3, PC3, A375, AGS, MCF-7, and WRL-68 hepatic cell lines. NADESs were prepared from choline chloride, fructose, or glucose and compared with an N,N-diethyl ethanolammonium chloride:triethylene glycol DES. The NADESs (98 ≤ EC50 ≥ 516 mM) were less toxic than the DES (34 ≤ EC50 ≥ 120 mM). The EC50 values of the NADESs were significantly higher than those of the aqueous solutions of their individual components but were similar to those of the aqueous solutions of combinations of their chief elements. Due to the uniqueness of these results, the possibility that NADESs could be synthesized intracellularly to counterbalance the cytotoxicity of their excess principal constituents must be entertained. However, further research is needed to explore this avenue. NADESs exerted cytotoxicity by increasing membrane porosity and redox stress. In vivo, they were more destructive than the DES and induced liver failure. The potential of these mixtures was evidenced by their anticancer activity and intracellular processing. This infers that they can serve as tools for increasing our understanding of cell physiology and metabolism. It is likely that we only have begun to comprehend the nature of NADESs. PMID:28145498

Ecotoxicological effects of copper and selenium combined pollution on soil enzyme activities in planted and unplanted soils.

PubMed

Hu, Bin; Liang, Dongli; Liu, Juanjuan; Xie, Junyu

2013-04-01

The present study explored the joint effects of Cu and Se pollution mechanisms on soil enzymes to provide references for the phytoremediation of contaminated areas and agricultural environmental protection. Pot experiments and laboratory analyses were carried out to study the individual and combined influences of Cu and Se on soil enzyme activities. The activities of four soil enzymes (urease, catalase, alkaline phosphatase, and nitrate reductase) were chosen. All soil enzyme activities tested were inhibited by Cu and Se pollution, either individually or combined, in varying degrees, following the order nitrate reductase>urease>catalase>alkaline phosphatase. Growing plants stimulated soil enzyme activity in a similar trend compared with treatments without plants. The joint effects of Cu and Se on catalase activity showed synergism at low concentrations and antagonism at high concentrations, whereas the opposite was observed for urease activity. However, nitrate reductase activity showed synergism both with and without plant treatments. The half maximal effective concentration (EC50) of exchangeable fractions had a similar trend with the EC50 of total content and was lower than that of total content. The EC50 values of nitrate reductase and urease activities were significantly lower for both Se and Cu (p<0.05), which indicated that they were more sensitive than the other two enzymes. Copyright © 2013 SETAC.

Unraveling the cytotoxicity and metabolic pathways of binary natural deep eutectic solvent systems

NASA Astrophysics Data System (ADS)

Mbous, Yves Paul; Hayyan, Maan; Wong, Won Fen; Looi, Chung Yeng; Hashim, Mohd Ali

2017-02-01

In this study, the anticancer potential and cytotoxicity of natural deep eutectic solvents (NADESs) were assessed using HelaS3, PC3, A375, AGS, MCF-7, and WRL-68 hepatic cell lines. NADESs were prepared from choline chloride, fructose, or glucose and compared with an N,N-diethyl ethanolammonium chloride:triethylene glycol DES. The NADESs (98 ≤ EC50 ≥ 516 mM) were less toxic than the DES (34 ≤ EC50 ≥ 120 mM). The EC50 values of the NADESs were significantly higher than those of the aqueous solutions of their individual components but were similar to those of the aqueous solutions of combinations of their chief elements. Due to the uniqueness of these results, the possibility that NADESs could be synthesized intracellularly to counterbalance the cytotoxicity of their excess principal constituents must be entertained. However, further research is needed to explore this avenue. NADESs exerted cytotoxicity by increasing membrane porosity and redox stress. In vivo, they were more destructive than the DES and induced liver failure. The potential of these mixtures was evidenced by their anticancer activity and intracellular processing. This infers that they can serve as tools for increasing our understanding of cell physiology and metabolism. It is likely that we only have begun to comprehend the nature of NADESs.

Building-related symptoms are linked to the in vitro toxicity of indoor dust and airborne microbial propagules in schools: A cross-sectional study.

PubMed

Salin, J T; Salkinoja-Salonen, M; Salin, P J; Nelo, K; Holma, T; Ohtonen, P; Syrjälä, H

2017-04-01

Indoor microbial toxicity is suspected to cause some building-related symptoms, but supporting epidemiological data are lacking. We examined whether the in vitro toxicity of indoor samples from school buildings was associated with work-related health symptoms (building-related symptoms, BRS). Administrators of the Helsinki City Real Estate Department selected 15 schools for the study, and a questionnaire on symptoms connected to work was sent to the teachers in the selected schools for voluntary completion. The cellular toxicity of classroom samples was determined by testing substances extracted from wiped indoor dust and by testing microbial biomass that was cultured on fallout plates. Boar sperm cells were used as indicator cells, and motility loss was the indicator for toxic effects. The effects were expressed as the half maximal effective concentration (EC 50 ) at which >50% of the exposed boar sperm cells were immobile compared to vehicle control. Completed symptom questionnaires were received from 232 teachers [median age, 43 years; 190 (82.3%) women] with a median time of 6 years working at their school. Samples from their classrooms were available and were assessed for cellular toxicity. The Poisson regression model showed that the impact of extracts of surface-wiped school classroom dust on teacher work-related BRS was 2.8-fold (95% CI: 1.6-4.9) higher in classrooms with a toxic threshold EC 50 of 6µgml -1 versus classrooms with insignificant EC 50 values (EC 50 >50µgml -1 ); P<0.001. The number of symptoms that were alleviated during vacation was higher in school classrooms with high sperm toxicity compared to less toxic sites; the RR was 1.9 (95% CI: 1.1-3.3, P=0.03) for wiped dust extracts. Teachers working in classrooms where the samples showed high sperm toxicity had more BRS. The boar sperm cell motility inhibition assay appears promising as a tool for demonstrating the presence of indoor substances associated with BRS. Copyright © 2017 Elsevier Inc. All rights reserved.

An efficient laboratory workflow for environmental risk assessment of organic chemicals.

PubMed

Zhu, Linyan; Santiago-Schübel, Beatrix; Xiao, Hongxia; Thiele, Björn; Zhu, Zhiliang; Qiu, Yanling; Hollert, Henner; Küppers, Stephan

2015-07-01

In this study, we demonstrate a fast and efficient workflow to investigate the transformation mechanism of organic chemicals and evaluate the toxicity of their transformation products (TPs) in laboratory scale. The transformation process of organic chemicals was first simulated by electrochemistry coupled online to mass spectrometry (EC-MS). The simulated reactions were scaled up in a batch EC reactor to receive larger amounts of a reaction mixture. The mixture sample was purified and concentrated by solid phase extraction (SPE) for the further ecotoxicological testing. The combined toxicity of the reaction mixture was evaluated in fish egg test (FET) (Danio rerio) compared to the parent compound. The workflow was verified with carbamazepine (CBZ). By using EC-MS seven primary TPs of CBZ were identified; the degradation mechanism was elucidated and confirmed by comparison to literature. The reaction mixture and one primary product (acridine) showed higher ecotoxicity in fish egg assay with 96 h EC50 values of 1.6 and 1.0 mg L(-1) than CBZ with the value of 60.8 mg L(-1). The results highlight the importance of transformation mechanism study and toxicological effect evaluation for organic chemicals brought into the environment since transformation of them may increase the toxicity. The developed process contributes a fast and efficient laboratory method for the risk assessment of organic chemicals and their TPs. Copyright © 2015 Elsevier Ltd. All rights reserved.

N2C2M2 Experimentation and Validation: Understanding Its C2 Approaches and Implications

DTIC Science & Technology

2010-06-01

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Exploration of (hetero)aryl derived thienylchalcones for antiviral and anticancer activities.

PubMed

Patil, Vikrant; Patil, Siddappa A; Patil, Renukadevi; Bugarin, Alejandro; Beaman, Kenneth; Patil, Shivaputra A

2018-05-23

Search for new antiviral and anticancer agents are essential because of the emergence of drug resistance in recent years. In continuation of our efforts in identifying the new small molecule antiviral and anticancer agents, we identified chalcones as potent antiviral and anticancer agents. With the aim of identifying the broad acting antiviral and anticancer agents, we discovered substituted aryl/heteroaryl derived thienyl chalcones as antiviral and anticancer agents. A focused set of thienyl chalcone derivaties II-VI was screened for selected viruses Hepatitis B virus (HBV), Herpes simplex virus 1 (HSV-1), Human cytomegalovirus (HCMV), Dengue virus 2 (DENV2), Influenza A (H1N1) virus, MERS coronavirus, Poliovirus 1 (PV 1), Rift Valley fever (RVF), Tacaribe virus (TCRV), Venezuelan equine encephalitis virus (VEE) and Zika virus (ZIKV) using the National Institute of Allergy and Infectious Diseases (NIAID)'s Division of Microbiology and Infectious Diseases (DMID) antiviral screening program. Additionally, a cyclopropylquinoline derivative IV has been screened for 60 human cancer cell lines using the Development Therapeutics Program (DTP) of NCI. All thienyl chalcone derivatives II-VI displayed moderate to excellent antiviral activity towards several viruses tested. Compounds V and VI were turned out be active compounds towards human cytomegalovirus for both normal strain (AD169) as well as resistant isolate (GDGr K17). Particularly, cyano derivative V showed very high potency (EC50: <0.05 µM) towards AD169 strain of HCMV compared to standard drug Ganciclovir (EC50: 0.12 µM). Additionally, it showed moderate activity in the secondary assay (AD169; EC50: 2.30 µM). The cyclopropylquinoline derivative IV displayed high potency towards Rift Valley fever virus (RVFV) and Tacaribe virus (TCRV). The cyclopropylquinoline derivative IV is nearly 28 times more potent in our initial in vitro visual assay (EC50: 0.39 μg/ml) and nearly 17 times more potent in neutral red assay (EC50: 0.71 μg/ml) compared to the standard drug Ribavirin (EC50: 11 μg/ml; visual assay and EC50: 12 μg/ml; neutral red assay). It is nearly 12 times more potent in our initial in vitro visual assay (EC50: >1 μg/ml) and nearly 8 times more potent in neutral red assay (EC50: >1.3 μg/ml) compared to the standard drug Ribavirin (EC50: 12 μg/ml; visual assay and EC50: 9.9 μg/ml; neutral red assay) towards Tacaribe virus (TCRV). Additionally, cyclopropylquinoline derivative IV has shown strong growth inhibitory activity towards three major cancer (colon, breast, and leukemia) cell lines and moderate growth inhibition shown towards other cancer cell lines screened. Compounds V and VI were demonstrated viral inhibition towards Human cytomegalovirus, whereas cyclopropylquinoline derivative IV towards Rift Valley fever virus and Tacaribe virus. Additionally, cyclopropylquinoline derivative IV has displayed very good cytotoxicity against colon, breast and leukemia cell lines in vitro. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Gold nanoparticle-aided brachytherapy with vascular dose painting: estimation of dose enhancement to the tumor endothelial cell nucleus.

PubMed

Ngwa, Wilfred; Makrigiorgos, G Mike; Berbeco, Ross I

2012-01-01

Theoretical microdosimetry at the subcellular level is employed in this study to estimate the dose enhancement to tumor endothelial cell nuclei, caused by radiation-induced photo/Auger electrons originating from gold nanoparticles (AuNPs) targeting the tumor endothelium, during brachytherapy. A tumor vascular endothelial cell (EC) is modeled as a slab of 2 μm (thickness) × 10 μm (length) × 10 μm (width). The EC contains a nucleus of 5 μm diameter and thickness of 0.5-1 μm, corresponding to nucleus size 5%-10% of cellular volume, respectively. Analytic calculations based on the electron energy loss formula of Cole were carried out to estimate the dose enhancement to the nucleus caused by photo/Auger electrons from AuNPs attached to the exterior surface of the EC. The nucleus dose enhancement factor (nDEF), representing the ratio of the dose to the nucleus with and without the presence of gold nanoparticles was calculated for different AuNP local concentrations. The investigated concentration range considers the potential for significantly higher local concentration near the EC due to preferential accumulation of AuNP in the tumor vasculature. Four brachytherapy sources: I-125, Pd-103, Yb-169, and 50 kVp x-rays were investigated. For nucleus size of 10% of the cellular volume and AuNP concentrations ranging from 7 to 140 mg/g, brachytherapy sources Pd-103, I-125, 50 kVp, and Yb-169 yielded nDEF values of 5.6-73, 4.8-58.3, 4.7-56.6, and 3.2-25.8, respectively. Meanwhile, for nucleus size 5% of the cellular volume in the same concentration range, Pd-103, I-125, 50 kVp, and Yb-169 yielded nDEF values of 6.9-79.2, 5.1-63.2, 5.0-61.5, and 3.3-28.3, respectively. The results predict that a substantial dose boost to the nucleus of endothelial cells can be achieved by applying tumor vasculature-targeted AuNPs in combination with brachytherapy. Such vascular dose boosts could induce tumor vascular shutdown, prompting extensive tumor cell death.

Improving in vitro to in vivo extrapolation by incorporating toxicokinetic measurements: A case study of lindane-induced neurotoxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Croom, Edward L.; Shafer, Timothy J.; Evans, Marina V.

Approaches for extrapolating in vitro toxicity testing results for prediction of human in vivo outcomes are needed. The purpose of this case study was to employ in vitro toxicokinetics and PBPK modeling to perform in vitro to in vivo extrapolation (IVIVE) of lindane neurotoxicity. Lindane cell and media concentrations in vitro, together with in vitro concentration-response data for lindane effects on neuronal network firing rates, were compared to in vivo data and model simulations as an exercise in extrapolation for chemical-induced neurotoxicity in rodents and humans. Time- and concentration-dependent lindane dosimetry was determined in primary cultures of rat cortical neuronsmore » in vitro using “faux” (without electrodes) microelectrode arrays (MEAs). In vivo data were derived from literature values, and physiologically based pharmacokinetic (PBPK) modeling was used to extrapolate from rat to human. The previously determined EC{sub 50} for increased firing rates in primary cultures of cortical neurons was 0.6 μg/ml. Media and cell lindane concentrations at the EC{sub 50} were 0.4 μg/ml and 7.1 μg/ml, respectively, and cellular lindane accumulation was time- and concentration-dependent. Rat blood and brain lindane levels during seizures were 1.7–1.9 μg/ml and 5–11 μg/ml, respectively. Brain lindane levels associated with seizures in rats and those predicted for humans (average = 7 μg/ml) by PBPK modeling were very similar to in vitro concentrations detected in cortical cells at the EC{sub 50} dose. PBPK model predictions matched literature data and timing. These findings indicate that in vitro MEA results are predictive of in vivo responses to lindane and demonstrate a successful modeling approach for IVIVE of rat and human neurotoxicity. - Highlights: • In vitro to in vivo extrapolation for lindane neurotoxicity was performed. • Dosimetry of lindane in a micro-electrode array (MEA) test system was assessed. • Cell concentrations at the MEA EC{sub 50} equaled rat brain levels associated with seizure. • PBPK-predicted human brain levels at seizure also equaled EC{sub 50} cell concentrations. • In vitro MEA results are predictive of lindane in vivo dose–response in rats/humans.« less

Synthesis and in vitro anthelmintic properties of some new dithiaarsanes.

PubMed

Loiseau, P M; Lubert, P; Wolf, J G

1999-11-01

Fifteen new trivalent organoarsenicals were synthesized and evaluated for anthelmintic properties on three in vitro models, infective larvae of the filaria Molinema dessetae, infective larvae of an intestinal nematode, Nippostrongylus brasiliensis and adults and larvae of Rhabditis pseudoelongata a free living nematode. On the M. dessetae model, the most active compound after a 24 h incubation period had an EC50 of 0.02 mumol/l (compound 3a). Twelve compounds had an EC50 lower than 1 mumol/l whereas potassium melarsonyl exhibited an EC50 of 45.6 mumol/l. After 7 days incubation time, compound 1d had an EC50 of 2 nmol/l. On the N. brasiliensis model, compound 1d was also the most efficient after a 4 day incubation period (EC50 of 1 mumol/l). This compound was 100 times more active than potassium melarsonyl used as a reference compound. Nevertheless, no compound had an EC50 less than 100 mumol/l on Rhabditis pseudoelongata. Concerning the effect of dithiol ligands on the anthelmintic activity of these trivalent organoarsenicals on M. dessetae and N. brasiliensis, 2,2'-dimercaptodiethyloxide was more efficient as dithiol ligand than 1,3-dimercaptopropane which was more efficient than 1,2-dimercaptoethane. Moreover, the para-amino haptophore was more efficient than the melaminyl haptophore. These results showed that the use of new dithiol ligands for trivalent arsenicals enhanced greatly the anthelmintic activity compared with potassium melarsonyl.

Acute toxicity of endosulfan 35EC to two freshwater bivalve molluscs from Godavari river at Maharashtra State, India.

PubMed

Mane, U H; Muley, D V

1984-11-01

Static bioassay tests were conducted using commercial grade endosulfan 35EC to study its toxicity during different seasons to two species of Lamellidens from the Godavari river at Paithan (Maharashtra State). Acute toxicity studies for 96 h showed that both species of Lamellidens were more sensitive to endosulfan 35EC in summer, at times of high temperature, pH and total carbonate content of the water used, than in monsoon and winter. LC0 and LC50 values were determined for L. corrianus and L. marginalis, during summer, monsoon and winter. Statistical analyses showed that both species were more sensitive during summer (P less than 0.001) than in monsoon and winter and that L. marginalis was more sensitive to endosulfan 35EC than L. corrianus in summer (P less than 0.001). Behavioural changes and mortality of the bivalves were dose-related. Regression equations and 95% confidence limits for each species were established in different studies. The results are discussed in the light of possible effects of endosulfan on these species of bivalve molluscs.

The Endocannabinoid Reuptake Inhibitor WOBE437 Is Orally Bioavailable and Exerts Indirect Polypharmacological Effects via Different Endocannabinoid Receptors.

PubMed

Reynoso-Moreno, Inés; Chicca, Andrea; Flores-Soto, Mario E; Viveros-Paredes, Juan M; Gertsch, Jürg

2018-01-01

Different anandamide (AEA) transport inhibitors show antinociceptive and antiinflammatory effects in vivo , but due to their concomitant inhibition of fatty acid amide hydrolase (FAAH) and overall poor bioavailability, they cannot be used unequivocally to study the particular role of endocannabinoid (EC) transport in pathophysiological conditions in vivo . Here, the potent and selective endocannabinoid reuptake inhibitor WOBE437, which inhibits AEA and 2-arachidonoylglycerol (2-AG) transport, was tested for its oral bioavailability to the brain. WOBE437 is assumed to locally increase EC levels in tissues in which facilitated EC reuptake intermediates subsequent hydrolysis. Given the marked polypharmacology of ECs, we hypothesized to see differential effects on distinct EC receptors in animal models of acute and chronic pain/inflammation. In C57BL6/J male mice, WOBE437 was orally bioavailable with an estimated t max value of ≤20 min in plasma (C max ∼ 2000 pmol/mL after 50 mg/kg, p.o.) and brain (C max ∼ 500 pmol/g after 50 mg/kg, p.o.). WOBE437 was cleared from the brain after approximately 180 min. In addition, in BALB/c male mice, acute oral administration of WOBE437 (50 mg/kg) exhibited similar brain concentrations after 60 min and inhibited analgesia in the hot plate test in a cannabinoid CB1 receptor-dependent manner, without inducing catalepsy or affecting locomotion. WOBE437 significantly elevated AEA in the somatosensory cortex, while showing dose-dependent biphasic effects on 2-AG levels in plasma but no significant changes in N -acylethanolamines other than AEA in any of the tissues. In order to explore the presumed polypharmacology mediated via elevated EC levels, we tested this EC reuptake inhibitor in complete Freud's adjuvant induced monoarthritis in BALB/c mice as a model of chronic inflammation. Repetitive doses of WOBE437 (10 mg/kg, i.p.) attenuated allodynia and edema via cannabinoid CB2, CB1, and PPARγ receptors. The allodynia inhibition of WOBE437 treatment for 3 days was fully reversed by antagonists of any of the receptors. In the single dose treatment the CB2 and TRPV1 antagonists significantly blocked the effect of WOBE437. Overall, our results show the broad utility of WOBE437 for animal experimentation for both p.o. and i.p. administrations. Furthermore, the data indicate the possible involvement of EC reuptake/transport in pathophysiological processes related to pain and inflammation.

Use of refractometry as a new management tool in AI boar centers for quality assurance of extender preparations.

PubMed

Schulze, M; Rüdiger, K; Jung, M; Grossfeld, R

2015-01-01

A study was performed to see if refractometry can be used as a new quality control tool for boar semen extenders. For this the refractive index and osmolality of BTS extender concentrations (EC) were recorded in 10%-steps from 50% to 150% and 200% of the correct amount. Twelve boar ejaculates were evaluated for semen quality. The refractive index for the correctly prepared extender was 4.6±0.0°Bx, corresponded to 316±16mOsmkg(-1), and correlated highly with osmolality (r=0.99; P<0.001). Total sperm motility with 100% EC differed significantly from ≤70% EC (P<0.001) and 200% EC (P<0.001) on day 1 (d1) and d4, respectively. The percentage of motile spermatozoa in a thermoresistance test on d2 showed a significant drop using ≤70% EC (P=0.047) and ≥140% EC (P=0.004). Secondary apical ridge defects were significantly higher using 50% EC (P<0.001) and ≥150% EC (P=0.032) compared to 100% EC, respectively. An increased number of coiled tails were observed using ≤60% EC (P<0.001). Percentages of spermatozoa with intact membranes on d2 resulted in a significant decrease using 50% EC (P<0.001) and ≥150% EC (P=0.005), respectively. The mean percentage of PI negative spermatozoa with active mitochondria on d2 showed a significant difference using ≤60% EC (P=0.016) and ≥140% EC (P<0.001) compared to 100% EC, respectively. Boar sperm quality is affected by inexact extender preparation. The refractive-index is an indicator of osmolality and may be used to verify semen extender preparation. The sensitivity is sufficient to detect deviations from correct extender preparation before negative effects on sperm quality occur. Copyright © 2014 Elsevier B.V. All rights reserved.

Interaction of xenobiotics on the glucose-transport system and the Na+/K(+)-ATPase of human skin fibroblasts.

PubMed

Cascorbi, I; Forêt, M

1991-02-01

The effects of individual and combined xenobiotics on functional properties of the plasma membrane of human skin fibroblasts were investigated. Good correlations between toxic effects on the D-glucose transport system or the Na+/K(+)-ATPase and the lipophilicity of the substances could be observed. The linear regression coefficients plotting log EC20 values (doses, leading to 20% inhibition) versus log Pow (octanol/water partition coefficient) were r = 0.95 (P less than 0.05). The combination of lipophilic with less lipophilic xenobiotics, such as pentachlorophenol with 4-chloroaniline, leads to additional effects. However, when the detergent sodium dodecyl benzenesulfonate was combined with the herbicide 2,4-dichlorophenoxyacetate (2,4-D), the toxic effect of 2,4-D on the Na+/K(+)-ATPase decreased considerably. The results support in general the assumption that the inhibition of integral functional proteins is based on an accumulation of xenobiotics in the plasma membrane, probably due to the enhanced membrane fluidity. Thus, the basic toxicity of xenobiotics can be predicted by their physicochemical properties.

Sorption behavior of 17 phthalic acid esters on three soils: effects of pH and dissolved organic matter, sorption coefficient measurement and QSPR study.

PubMed

Yang, Fen; Wang, Meng; Wang, Zunyao

2013-09-01

This work studies the sorption behaviors of phthalic acid esters (PAEs) on three soils by batch equilibration experiments and quantitative structure property relationship (QSPR) methodology. Firstly, the effects of soil type, dissolved organic matter and pH on the sorption of four PAEs (DMP, DEP, DAP, DBP) are investigated. The results indicate that the soil organic carbon content has a crucial influence on sorption progress. In addition, a negative correlation between pH values and the sorption capacities was found for these four PAEs. However, the effect of DOM on PAEs sorption may be more complicated. The sorption of four PAEs was promoted by low concentrations of DOM, while, in the case of high concentrations, the influence of DOM on the sorption was complicated. Then the organic carbon content normalized sorption coefficient (logKoc) values of 17 PAEs on three soils were measured, and the mean values ranged from 1.50 to 7.57. The logKoc values showed good correlation with the corresponding logKow values. Finally, two QSPR models were developed with 13 theoretical parameters to get reliable logKoc predictions. The leave-one-out cross validation (CV-LOO) indicated that the internal predictive power of the two models was satisfactory. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Vibrational studies of flexible solid polymer electrolyte based on PCL-EC incorporated with proton conducting NH4SCN

NASA Astrophysics Data System (ADS)

Woo, H. J.; Arof, A. K.

2016-05-01

A flexible solid polymer electrolyte (SPE) system based on poly(ε-caprolactone) (PCL), a FDA approved non-toxic and biodegradable material in the effort to lower environmental impact was prepared. Ammonium thiocyanate (NH4SCN) and ethylene carbonate (EC) were incorporated as the source of charge carriers and plasticizing agent, respectively. When 50 wt.% of ethylene carbonate (EC) was added to PCL-NH4SCN system, the conductivity increased by two orders from of 3.94 × 10- 7 Scm- 1 to 3.82 × 10- 5 Scm- 1. Molecular vibrational analysis via infrared spectroscopy had been carried out to study the interaction between EC, PCL and NH4SCN. The relative percentage of free ions, ion pairs and ion aggregates was calculated quantitatively by deconvoluting the SCN- stretching mode (2030-2090 cm- 1). This study provides fundamental insight on how EC influences the free ion dissociation rate and ion mobility. The findings are also in good agreement to conductivity, differential scanning calorimetry and X-ray diffraction results. High dielectric constant value (89.8) of EC had made it an effective ion dissociation agent to dissociate both ion pairs and ion aggregates, thus contributing to higher number density of free ions. The incorporation of EC had made the polymer chains more flexible in expanding amorphous domain. This will facilitate the coupling synergy between ionic motion and polymer segmental motion. Possible new pathway through EC-NH4+ complex sites for ions to migrate with shorter distance has been anticipated. This implies an easier ion migration route from one complex site to another.

Age of Haemonchus contortus third stage infective larvae is a factor influencing the in vitro assessment of anthelmintic properties of tannin containing plant extracts.

PubMed

Castañeda-Ramírez, G S; Mathieu, C; Vilarem, G; Hoste, H; Mendoza-de-Gives, P; González-Pech, P G; Torres-Acosta, J F J; Sandoval-Castro, C A

2017-08-30

The larval exsheathment inhibition assay (LEIA) of infective larvae (L 3 ) is an in vitro method used to evaluate the anthelmintic (AH) activity of tannin-containing plant extracts against different species of gastrointestinal nematodes, including Haemonchus contortus. Some conditions remain to be defined in order to standardize the LEIA, i.e. the optimal age of larvae produced from donor animals to use in the assays. Therefore, this study aimed at identifying the effect of age and age-related vitality of H. contortus infective larvae produced under tropical conditions, on the in vitro AH activity measured with the LEIA. The same acetone:water (70:30) extract from Acacia pennatula leaves was used to perform respective LEIA tests with H. contortus L 3 of different ages (1-7 weeks). Each week, the L 3 were tested against different concentrations of extract (1200, 600, 400, 200, 100, 40μg/mL of extract) plus a PBS control. Bioassays were performed with a benzimidazole (Bz) resistant H. contortus (Paraíso) strain. In order to identify changes in L 3 vitality on different weeks (1-7), two assays testing larval motility were included only with PBS: the larval migration assay (LMA) and the larval motility observation assay (LMOA). Mean effective concentrations causing 50% and 90% exsheathment inhibition (EC 50 , EC 90 ) were obtained for every week using respective Probit analyses. On the first week, the larvae had lowest EC 50 and EC 90 (39.4 and 65.6μg/mL) compared to older larvae (P<0.05). The EC 50 and EC 90 for weeks 2-5 were similar (P>0.05), while older larvae tended to show higher EC 50 and EC 90 (P<0.05). Motility showed strong negative correlations with age of larvae (r≥-0.83; P <0.05) and EC 50 (r≥-0.80; P<0.05), suggesting that the lower extract efficacy could be associated with decaying vitality of larvae associated with age. More stable efficacy results were found between two to five weeks of age. Copyright © 2017 Elsevier B.V. All rights reserved.

M1/M2 muscarinic receptor selectivity using potassium (K/sup +/)-stimulated release of (/sup 3/H)-dopamine (DA) and (/sup 14/C)-acetyl-choline (ACH) in striatum

DOE Office of Scientific and Technical Information (OSTI.GOV)

DeHaven, D.L.; Steranka, L.R.

Raiteri et al have suggested that muscarinic receptor subtypes can be differentiated in striatal synaptosomes by the release of DA (M1) or ACh (M2). The authors attempted to replicate this finding and to characterize responses of selective and non-selective cholinergic agonists and antagonists using K+-stimulated release of transmitters from rat striatal slices. The non-selective agonists ACh, carbachol and oxotremorine stimulated release of (/sup 3/H)-DA and inhibited release of (/sup 14/C)-ACh with EC50 values of 10.6, 9.2 and 4.2 ..mu..M (DA) and 1.2, 0.77 and 0.43 ..mu..M (ACh), respectively. The M1 agonist McN-A-343-11 selectively inhibited release of DA with an EC50more » value of 4.8 ..mu..M. Pilocarpine was ineffective in this system. The M1 antagonist pirenzepine reversed the effects of 10/sup -4/ M carbachol on release with an eight-fold selectivity for release of (/sup 3/H)-DA (IC50 = 0.77 ..mu..M) vs (/sup 14/C)-ACh (IC50 = 6.3 ..mu..M). These results suggest that although this system can determine relative subtype selectivities, the results obtained in this assay do not always correlate with those obtained from phosphatidyl inositol turnover or adenylate cyclase activity.« less

Serum antibodies and DNA indicate a high prevalence of equine papillomavirus 2 (EcPV2) among horses in Switzerland.

PubMed

Fischer, Nina M; Favrot, Claude; Birkmann, Katharina; Jackson, Michele; Schwarzwald, Colin C; Müller, Martin; Tobler, Kurt; Geisseler, Marco; Lange, Christian E

2014-06-01

The DNA of equine papillomavirus type 2 (EcPV2) is consistently found in equine papillomas and squamous cell carcinomas, indicating a causal association of EcPV2 in the pathogenesis of these tumours; however, little is known about the prevalence of this virus. The aim of this study was to determine the geno- and seroprevalence of EcPV2 in clinically healthy horses in Switzerland. Fifty horses presented to the equine department of the university clinic, displaying no skin or mucous membrane lesions or severe signs of other diseases, were sampled. Cytobrush samples from the penis or vulva and serum samples were collected. To determine the genoprevalence of EcPV2, DNA was extracted from cytobrush samples and tested for viral DNA with a PCR assay amplifying a 338 bp fragment of the E7/E1 region of the viral genome. Seroprevalence was tested using an enzyme-linked immunosorbent assay aimed to detect antibodies against the major capsid protein (L1) of EcPV2. In five of 50 horses (10%), EcPV2-specific DNA was amplified but no antibodies could be detected, whereas in 14 of 50 horses (28%), antibodies against EcPV2 but no DNA were demonstrated. Both antibodies and viral DNA were detected in four of 50 horses (8%). Neither antibodies nor viral DNA were found in 27 of 50 horses (54%). The seroprevalence suggests that EcPV2 is prevalent in the Swiss equine population, while the genoprevalence indicates that currently ongoing infections are less common. The discrepancy between geno- and seroprevalence probably indicates different stages of infection in the tested cohort. © 2014 ESVD and ACVD.

Emergency contraception with a Copper IUD or oral levonorgestrel: an observational study of 1-year pregnancy rates

PubMed Central

Turok, David K.; Jacobson, Janet C.; Dermish, Amna I.; Simonsen, Sara E.; Gurtcheff, Shawn; McFadden, Molly; Murphy, Patricia A.

2014-01-01

Objective We investigated the one-year pregnancy rates for emergency contraception (EC) users who selected the copper T380 IUD or oral levonorgestrel (LNG) for EC. Study Design This prospective study followed women for 1 year after choosing either the copper T380 IUD or oral LNG for EC. The study was powered to detect a 6% difference in pregnancy rates within the year after presenting for EC. Results Of the 542 women who presented for EC, agreed to participate in the trial, and meet inclusion criteria, 215 (40%) chose the copper IUD and 327 (60%) chose oral LNG. In the IUD group, 127 (59%) were nulligravid. IUD insertion failed in 42 women (19%). The 1-year follow-up rate was 443/542 (82%); 64% of IUD users contacted at 1 year still had their IUDs in place. The 1-year cumulative pregnancy rate in women choosing the IUD was 6.5% vs. 12.2% in those choosing oral LNG (HR= 0.53, 95% CI: 0.29–0.97, p=0.041). By type of EC method actually received, corresponding values were 5.2% for copper IUD users vs. 12.3% for oral LNG users, HR 0.42 (95% CI: 0.20–0.85, p= 0.017). A multivariable logistic regression model controlling for demographic variables demonstrates that women who chose the IUD for EC had fewer pregnancies in the following year than those who chose oral LNG (HR 0.50, 95% CI: 0.26–0.96, p=0.037). Conclusion One year after presenting for EC women choosing the copper IUD for EC were half as likely to have a pregnancy compared to those choosing oral LNG. PMID:24332433

The role of dissolved organic carbon concentration and composition on nickel toxicity to early life-stages of the blue mussel Mytilus edulis and purple sea urchin Strongylocentrotus purpuratus.

PubMed

Blewett, Tamzin A; Dow, Elissa M; Wood, Chris M; McGeer, James C; Smith, D Scott

2018-05-24

Nickel (Ni) emissions resulting from production and transportation raise concerns about the impact of Ni exposure to marine ecosystems. Ni bioavailability models are established for FW systems, but the influence of chemical parameters (e.g. dissolved organic carbon (DOC)) on Ni toxicity within marine systems is less well understood. To examine the effects of DOC concentration and composition on Ni toxicity, acute toxicity tests were conducted on early life-stages of blue mussels (Mytilus edulis) and sea urchin embryos (Strongylocentrotus purpuratus) in full strength sea water (32 ppt). Nine different field collected samples of water with varying concentration (up to 4.5 mg C/L) and composition of DOC were collected from the east coast of the United States. Organic matter compositional analysis included molecular fluorescence and absorbance spectroscopy. The different DOC sources had different protective effects against embryo toxicity. The control (no DOC) Ni 48 h-EC 50 for Mytilus embryos was 133 µg/L (95% confidence interval (C.I.) of 123-144 µg/L), while Strongylocentrotus embryos displayed control 96-h EC 50 values of 207 µg/L (167-247 µg/L). The most significantly protective sample had high humic acid concentrations (as determined from fluorescence spectroscopy), which yielded an EC 50 of 195 µg/L (169-222 µg/L) for Mytilus, and an EC 50 of 394 µg/L (369-419 µg/L) for S. purpuratus. Among all samples, protection was related to both DOC quantity and quality, with fluorescence-resolved humic and fulvic acid concentrations showing the strongest correlations with protection for both species. These data suggest that DOC is protective against Ni toxicity in M. edulis and S. purpuratus, and that accounting for a DOC quality factor will improve predictive toxicity models such as the biotic ligand model. Copyright © 2018 Elsevier Inc. All rights reserved.

Regulation of the substance P-induced contraction via the release of acetylcholine and gamma-aminobutyric acid in the guinea-pig urinary bladder.

PubMed Central

Shirakawa, J.; Nakanishi, T.; Taniyama, K.; Kamidono, S.; Tanaka, C.

1989-01-01

1. The action of substance P (SP) on the release of gamma-aminobutyric acid (GABA) and acetylcholine (ACh) and on contraction were studied in strips of the guinea-pig urinary bladder. Substance P induced a dose-dependent contraction of strips of guinea-pig urinary bladder (EC50 = 1.2 x 10(-9) M). This contraction was not altered by tetrodotoxin, but with a dose of 10(-9) M and less, there was a complete inhibition by 10(-6) M) atropine. Contractions initiated by 3 x 10(-9) M) SP or more were partly inhibited by atropine. The EC50 value of substance P in the presence of atropine was 7.0 x 10(-9) M. 2. Substance P induced a Ca2+-dependent and tetrodotoxin-resistant release of [3H]-acetylcholine (ACh) from strips of urinary bladder preloaded with [3H]-choline (EC50 = 4.9 x 10(-10) M), and this release was antagonized by [D-Pro2,D-Trp7,9] substance P. 3. Bicuculline increased the substance P-induced contraction and the release of [3H]-ACh from the strips. 4. Substance P induced a Ca2+-dependent and tetrodotoxin-sensitive release of [3H]-gamma-aminobutyric acid (GABA) from strips preloaded with [3H]-GABA (EC50 = 2.6 x 10(-9) M), and this release was antagonized by [D-Pro2,D-Trp7,9] substance P. 5. Therefore, substance P appears to exert excitatory effects on the contractility of urinary bladder predominantly by stimulating its own receptor located on the cholinergic nerve terminals. GABA released by substance P inhibits stimulation of the cholinergic neurone. However, the direct action of substance P on the cholinergic neurone is more potent that the indirect action via GABA release. PMID:2479440

Evaluation of resin infiltration using quantitative light-induced fluorescence technology.

PubMed

Min, Ji-Hyun; Inaba, Daisuke; Kim, Baek-Il

2016-09-01

To determine whether quantitative light-induced fluorescence (QLF) technology can be used to classify the colour of teeth specimens before and after resin infiltration (RI) treatment, and calculate the correlation between the ΔF value and colour difference (ΔE) in fluorescence images of the specimens obtained using a QLF-digital (QLF-D) device. Sixty sound bovine permanent teeth specimens were immersed in demineralized solution. Two exposed windows were formed in each specimen, and RI treatment was applied to one of them. The ΔE values were obtained for the differences between a sound tooth surface (SS), an early dental caries surface (ECS) and an ECS treated with RI (RS) in white-light and fluorescence images obtained using QLF-D, respectively. The ΔF value was obtained from fluorescence images using dedicated software for QLF-D. The mean differences between the ΔE values obtained from the white-light and fluorescence images were analyzed by paired t-test. Pearson correlation analysis and Bland-Altman plots were applied to the differences between the ΔF value for ECS (ΔFSS-ECS) and the ΔE value between SS and ECS (ΔESS-ECS), and between the ΔF value for RS (ΔFSS-RS) and the ΔE value between SS and RS (ΔESS-RS) in fluorescence images. The ΔE values obtained from fluorescence images were three times higher than the ΔE values obtained from white-light images (p<0.001). Significant correlations were confirmed between ΔESS-ECS and ΔFSS-ECS (r=-0.492, p<0.001) and between ΔESS-RS and ΔFSS-RS (r=-0.661, p<0.001). QLF technology can be used to confirm the presence of RI in teeth. Copyright © 2016 Elsevier B.V. All rights reserved.

The Medicinal Timber Canarium patentinervium Miq. (Burseraceae Kunth.) Is an Anti-Inflammatory Bioresource of Dual Inhibitors of Cyclooxygenase (COX) and 5-Lipoxygenase (5-LOX).

PubMed

Mogana, R; Teng-Jin, K; Wiart, C

2013-01-01

The barks and leaves extracts of Canarium patentinervium Miq. (Burseraceae Kunth.) were investigated for cyclooxygenase (COX) and 5-lipoxygenase (LOX) inhibition via in vitro models. The corresponding antioxidative power of the plant extract was also tested via nonenzyme and enzyme in vitro assays. The ethanolic extract of leaves inhibited the enzymatic activity of 5-LOX, COX-1, and COX-2 with IC50 equal to 49.66 ± 0.02 μg/mL, 0.60 ± 0.01 μg/mL, and 1.07 ± 0.01 μg/mL, respectively, with selective COX-2 activity noted in ethanolic extract of barks with COX-1/COX-2 ratio of 1.22. The ethanol extract of barks confronted oxidation in the ABTS, DPPH, and FRAP assay with EC50 values equal to 0.93 ± 0.01 μg/mL, 2.33 ± 0.02 μg/mL, and 67.00 ± 0.32 μg/mL, respectively, while the ethanol extract of leaves confronted oxidation in β-carotene bleaching assay and superoxide dismutase (SOD) assay with EC50 value of 6.04 ± 0.02 μg/mL and IC50 value of 3.05 ± 0.01 μg/mL. The ethanol extract acts as a dual inhibitor of LOX and COX enzymes with potent antioxidant capacity. The clinical significance of these data is quite clear that they support a role for Canarium patentinervium Miq. (Burseraceae Kunth.) as a source of lead compounds in the management of inflammatory diseases.

New Drugs for Anemia Treatment Based on a New Understanding of the Mechanisms of Stress Erythropoiesis

DTIC Science & Technology

2014-09-01

GlaxoSmithKline for dyslipidemia . It is a potent and highly selective PPARα agonist (EC50 values are 6, 1100 and 6200 nM for human PPARα, PPARγ and PPARδ...red cells in culture. These PPARα receptor agonists, fenofibrate and GW7647, originally developed by for dyslipidemia , can be used in clinical trials

Point sources of emerging contaminants along the Colorado River Basin: Source water for the arid Southwestern United States

USGS Publications Warehouse

Jones-Lepp, Tammy L.; Sanchez, Charles; Alvarez, David A.; Wilson, Doyle C.; Taniguchi-Fu, Randi-Laurant

2012-01-01

Emerging contaminants (ECs) (e.g., pharmaceuticals, illicit drugs, personal care products) have been detected in waters across the United States. The objective of this study was to evaluate point sources of ECs along the Colorado River, from the headwaters in Colorado to the Gulf of California. At selected locations in the Colorado River Basin (sites in Colorado, Utah, Nevada, Arizona, and California), waste stream tributaries and receiving surface waters were sampled using either grab sampling or polar organic chemical integrative samplers (POCIS). The grab samples were extracted using solid-phase cartridge extraction (SPE), and the POCIS sorbents were transferred into empty SPEs and eluted with methanol. All extracts were prepared for, and analyzed by, liquid chromatography–electrospray-ion trap mass spectrometry (LC–ESI-ITMS). Log DOW values were calculated for all ECs in the study and compared to the empirical data collected. POCIS extracts were screened for the presence of estrogenic chemicals using the yeast estrogen screen (YES) assay. Extracts from the 2008 POCIS deployment in the Las Vegas Wash showed the second highest estrogenicity response. In the grab samples, azithromycin (an antibiotic) was detected in all but one urban waste stream, with concentrations ranging from 30 ng/L to 2800 ng/L. Concentration levels of azithromycin, methamphetamine and pseudoephedrine showed temporal variation from the Tucson WWTP. Those ECs that were detected in the main surface water channels (those that are diverted for urban use and irrigation along the Colorado River) were in the region of the limit-of-detection (e.g., 10 ng/L), but most were below detection limits.

Carbon fluxes in tropical forest ecosystems: the value of Eddy-covariance data for individual-based dynamic forest gap models

NASA Astrophysics Data System (ADS)

Roedig, Edna; Cuntz, Matthias; Huth, Andreas

2015-04-01

The effects of climatic inter-annual fluctuations and human activities on the global carbon cycle are uncertain and currently a major issue in global vegetation models. Individual-based forest gap models, on the other hand, model vegetation structure and dynamics on a small spatial (<100 ha) and large temporal scale (>1000 years). They are well-established tools to reproduce successions of highly-diverse forest ecosystems and investigate disturbances as logging or fire events. However, the parameterizations of the relationships between short-term climate variability and forest model processes are often uncertain in these models (e.g. daily variable temperature and gross primary production (GPP)) and cannot be constrained from forest inventories. We addressed this uncertainty and linked high-resolution Eddy-covariance (EC) data with an individual-based forest gap model. The forest model FORMIND was applied to three diverse tropical forest sites in the Amazonian rainforest. Species diversity was categorized into three plant functional types. The parametrizations for the steady-state of biomass and forest structure were calibrated and validated with different forest inventories. The parameterizations of relationships between short-term climate variability and forest model processes were evaluated with EC-data on a daily time step. The validations of the steady-state showed that the forest model could reproduce biomass and forest structures from forest inventories. The daily estimations of carbon fluxes showed that the forest model reproduces GPP as observed by the EC-method. Daily fluctuations of GPP were clearly reflected as a response to daily climate variability. Ecosystem respiration remains a challenge on a daily time step due to a simplified soil respiration approach. In the long-term, however, the dynamic forest model is expected to estimate carbon budgets for highly-diverse tropical forests where EC-measurements are rare.

Phytochemistry and nematicidal activity of the essential oils from 8 Greek Lamiaceae aromatic plants and 13 terpene components.

PubMed

Ntalli, Nikoletta G; Ferrari, Federico; Giannakou, Ioannis; Menkissoglu-Spiroudi, Urania

2010-07-14

Eight essential oils (EOs) as well as 13 single terpenes were studied for their nematicidal activity against Meloidogyne incognita , for three immersion periods (24, 48, and 96 h). The EOs were isolated from eight Greek Lamiaceae species: Melissa officinalis , Sideritis clandestina , Origanum dictamnus , Ocimum basilicum , Mentha pulegium , Origanum vulgare , Vitex agnus castus , and Salvia officinalis . The EOs nematicidal activity was correlated to their chemical composition as well as to the pure terpenes' activity tested individually. Clear dose and time response relationships were established. The EOs of O. vulgare, O. dictamnus, M. pulegium, and M. officinalis exhibited high nematicidal activity against M. incognita, and the EC(50) values (96 h) were calculated at 1.55, 1.72, 3.15, and 6.15 muL/mL, respectively. The activity of the nematicidal terpenes was found to decrease in the order l-carvone, pulegone, trans-anethole, geraniol, eugenol, carvacrol, thymol, terpinen-4-ol, and the respective EC(50) values (24 h) were calculated in the range of 115-392 mug/mL. Terpenes tested individually were more active than as components in EO, implementing antagonistic action.

Reduced density gradient as a novel approach for estimating QSAR descriptors, and its application to 1, 4-dihydropyridine derivatives with potential antihypertensive effects.

PubMed

Jardínez, Christiaan; Vela, Alberto; Cruz-Borbolla, Julián; Alvarez-Mendez, Rodrigo J; Alvarado-Rodríguez, José G

2016-12-01

The relationship between the chemical structure and biological activity (log IC 50 ) of 40 derivatives of 1,4-dihydropyridines (DHPs) was studied using density functional theory (DFT) and multiple linear regression analysis methods. With the aim of improving the quantitative structure-activity relationship (QSAR) model, the reduced density gradient s( r) of the optimized equilibrium geometries was used as a descriptor to include weak non-covalent interactions. The QSAR model highlights the correlation between the log IC 50 with highest molecular orbital energy (E HOMO ), molecular volume (V), partition coefficient (log P), non-covalent interactions NCI(H4-G) and the dual descriptor [Δf(r)]. The model yielded values of R 2 =79.57 and Q 2 =69.67 that were validated with the next four internal analytical validations DK=0.076, DQ=-0.006, R P =0.056, and R N =0.000, and the external validation Q 2 boot =64.26. The QSAR model found can be used to estimate biological activity with high reliability in new compounds based on a DHP series. Graphical abstract The good correlation between the log IC 50 with the NCI (H4-G) estimated by the reduced density gradient approach of the DHP derivatives.

Genotoxicity Assessment of Volatile Organic Compounds in Landfill Gas Emission Using Comet Assay in Higher Terrestrial Plant.

PubMed

Na Roi-Et, Veerapas; Chiemchaisri, Wilai; Chiemchaisri, Chart

2017-02-01

Genotoxicity model is developed to assess the individual subacute toxicity of benzene, toluene, ethylbenzene, and xylene (BTEX) at very low levels as in a landfill gas. Golden Pothos (Epipremnum aureum), a higher plant, was tested under variation of benzene 54-5656 ng/L, toluene 10-4362 ng/L, ethylbenzene 28-4997 ng/L, xylene 53-4845 ng/L, for 96 h. DNA fragmentation in plant leaves were investigated via comet assay. The results show that DNA migration ratio increased with the BTEX concentrations, but at different rates. The 50% effective concentration (EC 50 ) of DNA fragmentation from the dose-response relationships indicated toluene has the highest EC 50 value and followed by benzene, xylene and ethylbenzene. Alternatively, ethylbenzene has the highest toxicity unit and followed by xylene, benzene and toluene as described by toxicity unit (TU). In conclusion, comet assay of Pothos can be used in differentiating DNA fragmentation against very low levels of BTEX in the atmosphere. Pothos is recommended for genotoxicity assessment of a low BTEX contaminated atmosphere.

SYNTHESIS AND ANTIVIRAL EVALUATION OF 9-(S)-[3-ALKOXY-2-(PHOSPHONOMETHOXY)PROPYL]NUCLEOSIDE ALKOXYALKYL ESTERS: INHIBITORS OF HEPATITIS C VIRUS AND HIV-1 REPLICATION

PubMed Central

Valiaeva, Nadejda; Wyles, David L.; Schooley, Robert T.; Hwu, Julia B.; Beadle, James R.; Prichard, Mark N.

2011-01-01

We reported previously that octadecyloxyethyl 9-(S)-[3-hydroxy-2-(phosphonomethoxy)-propyl]adenine (ODE-(S)-HPMPA) was active against genotype 1b and 2a hepatitis C virus (HCV) replicons. This is surprising because acyclic nucleoside phosphonates have been regarded as having antiviral activity only against double stranded DNA viruses, HIV and HBV. We synthesized octadecyloxyethyl 9-(S)-[3-methoxy-2-(phosphonomethoxy)propyl]-adenine and found it to be active in genotype 1b and 2a HCV replicons with EC50 values of 1-2 μM and a CC50 of>150 μM. Analogs with substitutions at the 3′-hydroxyl larger than methyl or ethyl, or with other purine bases were less active but most compounds had significant antiviral activity against HIV-1 in vitro. The most active anti-HIV compound was octadecyloxyethyl 9-(R)-[3-methoxy-2-(phosphonomethoxy)propyl]guanine with an EC50 <0.01 nanomolar and a selectivity index of>4.4 million. PMID:21719300

Aquatic toxicity of four alkylphenols (3-tert-butylphenol, 2-isopropylphenol, 3-isopropylphenol, and 4-isopropylphenol) and their binary mixtures to microbes, invertebrates, and fish.

PubMed

Choi, Kyungho; Sweet, Leonard I; Meier, Peter G; Kim, Pan-Gyi

2004-02-01

The acute and chronic toxicity of four simple alkylphenols with butyl and propyl substitutions was evaluated with aquatic microbes, invertebrates, and fish. These alkylphenols-3-tert-butylphenol, 2-isopropylphenol, 3-isopropylphenol, and 4-isopropylphenol-have been detected in various environmental media, but their impact on aquatic fauna has seldom been evaluated. Relative susceptibility to each phenolic varied by test species. The marine bacterium Vibrio fischeri was the most susceptible to the alkylphenols, up to 3 orders of magnitude more sensitive than species of higher trophic levels. For 4-isopropylphenol, the 5-min Microtox EC(50) value was 0.01 mg/L, whereas the EC(50) for Ceriodaphnia after a 48-h exposure was 10.1 mg/L. Notable differences in sensitivity to the alkylphenols was also observed with the Microtox assay: 4-isopropylphenol was > 200 times more toxic to V. fischeri than was 2-isopropylphenol (EC(50) = 2.72 mg/L). For V. fischeri, the mixture toxicity of the alkylphenols was additive in nature and was predicted by a concentration addition model. The energy of the lowest unoccupied molecular orbital (ELUMO) explained the observed toxicity of the individual alkylphenols to V. fischeri (r(2) = 0.92, p < 0.05). These results suggest that the mode of action of polar narcotic alkylphenols to V. fischeri is different than that of other test organisms, possibly because of the differences in the cell structure of the prokaryotic V. fischeri. Copyright 2004 Wiley Periodicals, Inc. Environ Toxicol 19: 45-50, 2004.

Comparison of protocols measuring diffusion and partition coefficients in the stratum corneum.

PubMed

Rothe, H; Obringer, C; Manwaring, J; Avci, C; Wargniez, W; Eilstein, J; Hewitt, N; Cubberley, R; Duplan, H; Lange, D; Jacques-Jamin, C; Klaric, M; Schepky, A; Grégoire, S

2017-07-01

Partition (K) and diffusion (D) coefficients are important to measure for the modelling of skin penetration of chemicals through the stratum corneum (SC). We compared the feasibility of three protocols for the testing of 50 chemicals in our main studies, using three cosmetics-relevant model chemicals with a wide range of logP values. Protocol 1: SC concentration-depth profile using tape-stripping (measures K SC/v and D SC /H SC 2 , where H SC is the SC thickness); Protocol 2A: incubation of isolated SC with chemical (direct measurement of K SC/v only) and Protocol 2B: diffusion through isolated SC mounted on a Franz cell (measures K SC/v and D SC /H SC 2 , and is based on Fick's laws). K SC/v values for caffeine and resorcinol using Protocol 1 and 2B were within 30% of each other, values using Protocol 2A were ~two-fold higher, and all values were within 10-fold of each other. Only indirect determination of K SC/v by Protocol 2B was different from the direct measurement of K SC/v by Protocol 2A and Protocol 1 for 7-EC. The variability of K SC/v for all three chemicals using Protocol 2B was higher compared to Protocol 1 and 2A. D SC /H SC 2 values for the three chemicals were of the same order of magnitude using all three protocols. Additionally, using Protocol 1, there was very little difference between parameters measured in pig and human SC. In conclusion, K SC/v, and D SC values were comparable using different methods. Pig skin might be a good surrogate for human skin for the three chemicals tested. Copyright © 2017 The Authors Journal of Applied Toxicology published by John Wiley & Sons Ltd. Copyright © 2017 The Authors Journal of Applied Toxicology published by John Wiley & Sons Ltd.

Synergistic and antagonistic interactions of terpenes against Meloidogyne incognita and the nematicidal activity of essential oils from seven plants indigenous to Greece.

PubMed

Ntalli, Nikoletta G; Ferrari, Federico; Giannakou, Ioannis; Menkissoglu-Spiroudi, Urania

2011-03-01

Biorational means for phytonematode control were studied within the context of an increasingly ecofriendly pest management global approach. The nematicidal activity and the chemical composition of essential oils (EOs) isolated from seven plants grown in Greece and ten selected compounds extracted from them against second-stage juveniles (J2) of Meloidogyne incognita (Kof. & White) Chitwood were evaluated using juvenile paralysis experiments. Additionally, synergistic and antagonistic interactions between nematicidal terpenes were studied using an effect addition model, with the comparison made at one concentration level. The 96 h EC(50) values of Foeniculum vulgare Mill., Pimpinella anisum L., Eucalyptus meliodora A Cunn ex Schauer and Pistacia terebinthus L. were 231, 269, 807 and 1116 µg mL(-1) , respectively, in an immersion bioassay. Benzaldehyde (9 µg mL(-1) ) was the most toxic compound, followed by γ-eudesmol (50 µg mL(-1) ) and estragole (180 µg mL(-1) ), based on 96 h EC(50) values. The most potent terpene pairs between which synergistic actions were found, in decreasing order, were: trans-anethole/geraniol, trans-anethole/eugenol, carvacrol/eugenol and geraniol/carvacrol. This is the first report on the activity of F. vulgare, P. anisum, E. meliodora and P. terebinthus, and additionally on synergistic/antagonistic nematicidal terpene interactions, against M. incognita, providing alternative methods for nematode control. Copyright © 2010 Society of Chemical Industry.

Involvement of alternative oxidase in the regulation of sensitivity of Sclerotinia sclerotiorum to the fungicides azoxystrobin and procymidone.

PubMed

Xu, Ting; Wang, Ya-Ting; Liang, Wu-Sheng; Yao, Fei; Li, Yong-Hong; Li, Dian-Rong; Wang, Hao; Wang, Zheng-Yi

2013-06-01

Sclerotinia sclerotiorum is a filamentous fungal pathogen that can infect many economically important crops and vegetables. Alternative oxidase is the terminal oxidase of the alternative respiratory pathway in fungal mitochondria. The function of alternative oxidase was investigated in the regulation of sensitivity of S. sclerotiorum to two commercial fungicides, azoxystrobin and procymidone which have different fungitoxic mechanisms. Two isolates of S. sclerotiorum were sensitive to both fungicides. Application of salicylhydroxamic acid, a specific inhibitor of alternative oxidase, significantly increased the values of effective concentration causing 50% mycelial growth inhibition (EC50) of azoxystrobin to both S. sclerotiorum isolates, whereas notably decreased the EC50 values of procymidone. In mycelial respiration assay azoxystrobin displayed immediate inhibitory effect on cytochrome pathway capacity, but had no immediate effect on alternative pathway capacity. In contrast, procymidone showed no immediate impact on capacities of both cytochrome and alternative pathways in the mycelia. However, alternative oxidase encoding gene (aox) transcript and protein levels, alternative respiration pathway capacity of the mycelia were obviously increased by pre-treatment for 24 h with both azoxystrobin and procymidone. These results indicate that alternative oxidase was involved in the regulation of sensitivity of S. sclerotiorum to the fungicides azoxystrobin and procymidone, and that both fungicides could affect aox gene expression and the alternative respiration pathway capacity development in mycelia of this fungal pathogen.

Emergency contraception with a copper IUD or oral levonorgestrel: an observational study of 1-year pregnancy rates.

PubMed

Turok, David K; Jacobson, Janet C; Dermish, Amna I; Simonsen, Sara E; Gurtcheff, Shawn; McFadden, Molly; Murphy, Patricia A

2014-03-01

We investigated the 1-year pregnancy rates for emergency contraception (EC) users who selected the copper T380 intrauterine device (IUD) or oral levonorgestrel (LNG) for EC. This prospective study followed women for 1 year after choosing either the copper T380 IUD or oral LNG for EC. The study was powered to detect a 6% difference in pregnancy rates within the year after presenting for EC. Of the 542 women who presented for EC, agreed to participate in the trial and met the inclusion criteria, 215 (40%) chose the copper IUD and 327 (60%) chose oral LNG. In the IUD group, 127 (59%) were nulligravid. IUD insertion failed in 42 women (19%). The 1-year follow-up rate was 443/542 (82%); 64% of IUD users contacted at 1 year still had their IUDs in place. The 1-year cumulative pregnancy rate in women choosing the IUD was 6.5% vs. 12.2% in those choosing oral LNG [hazard ratio (HR) 0.53, 95% confidence interval (CI): 0.29-0.97, p=.041]. By type of EC method actually received, corresponding values were 5.2% for copper IUD users vs. 12.3% for oral LNG users (HR 0.42, 95% CI: 0.20-0.85, p=.017). A multivariable logistic regression model controlling for demographic variables demonstrates that women who chose the IUD for EC had fewer pregnancies in the following year than those who chose oral LNG (HR 0.50, 95% CI: 0.26-0.96, p=.037). One year after presenting for EC, women choosing the copper IUD for EC were half as likely to have a pregnancy compared to those choosing oral LNG. Compared to EC users who choose oral levonorgestrel, those who select the copper IUD have lower rates of pregnancy in the next year. Greater use of the copper IUD for EC may lower rates of unintended pregnancy in high-risk women. Copyright © 2014 Elsevier Inc. All rights reserved.

Thresholds of copper phytotoxicity in field-collected agricultural soils exposed to copper mining activities in Chile.

PubMed

Verdejo, José; Ginocchio, Rosanna; Sauvé, Sébastien; Salgado, Eduardo; Neaman, Alexander

2015-12-01

It has been argued that the identification of the phytotoxic metal thresholds in soil should be based on field-collected soil rather than on artificially-contaminated soils. However, the use of field-collected soils presents several difficulties for interpretation because of mixed contamination and unavoidable covariance of metal contamination with other soil properties that affect plant growth. The objective of this study was to estimate thresholds of copper phytotoxicity in topsoils of 27 agricultural areas historically contaminated by mining activities in Chile. We performed emergence and early growth (21 days) tests (OECD 208 and ISO 11269-2) with perennial ryegrass (Lolium perenne L.). The total Cu content in soils was the best predictor of plant growth and shoot Cu concentrations, while soluble Cu and pCu(2+) did not well correlate with these biological responses. The effects of Pb, Zn, and As on plant responses were not significant, suggesting that Cu is a metal of prime concern for plant growth in soils exposed to copper mining activities in Chile. The effects of soil nutrient availability and shoot nutrient concentrations on ryegrass response were not significant. It was possible to determine EC10, EC25 and EC50 of total Cu in the soil of 327 mg kg(-1), 735 mg kg(-1) and 1144 mg kg(-1), respectively, using the shoot length as a response variable. However, the derived 95% confidence intervals for EC10, EC25 and EC50 values of total soil Cu were wide, and thus not allowing a robust assessment of metal toxicity for agricultural crops, based on total soil Cu concentrations. Thus, plant tests might need to be performed for metal toxicity assessment. This study suggests shoot length of ryegrass as a robust response variable for metal toxicity assessment in contaminated soils with different nutrient availability. Copyright © 2015 Elsevier Inc. All rights reserved.

Anti-HSV-1 and HSV-2 Flavonoids and a New Kaempferol Triglycoside from the Medicinal Plant Kalanchoe daigremontiana.

PubMed

Ürményi, Fernanda Gouvêa Gomes; Saraiva, Georgia do Nascimento; Casanova, Livia Marques; Matos, Amanda Dos Santos; de Magalhães Camargo, Luiza Maria; Romanos, Maria Teresa Villela; Costa, Sônia Soares

2016-12-01

Kalanchoe daigremontiana (Crassulaceae) is a medicinal plant native to Madagascar. The aim of this study was to investigate the flavonoid content of an aqueous leaf extract from K. daigremontiana (Kd), and assess its antiherpetic potential. The major flavonoid, kaempferol 3-O-β-d-xylopyranosyl-(1 → 2)-α-l-rhamnopyranoside (1), was isolated from the AcOEt fraction (Kd-AC). The BuOH-soluble fraction afforded quercetin 3-O-β-d-xylopyranosyl-(1 → 2)-α-l-rhamnopyranoside (2) and the new kaempferol 3-O-β-d-xylopyranosyl-(1 → 2)-α-l-rhamnopyranoside-7-O-β-d-glucopyranoside (3), named daigremontrioside. The crude extract, Kd-AC fraction, flavonoids 1 and 2 were evaluated using acyclovir-sensitive strains of HSV-1 and HSV-2. Kd-AC was highly active against HSV-1 (EC 50  = 0.97 μg/ml, SI > 206.1) and HSV-2 (EC 50  = 0.72 μg/ml, SI > 277.7). Flavonoids 1 and 2 showed anti-HSV-1 (EC 50  = 7.4 μg/ml; SI > 27 and EC 50  = 5.8 μg/ml; SI > 8.6, respectively) and anti-HSV-2 (EC 50  = 9.0 μg/ml; SI > 22.2 and EC 50  = 36.2 μg/ml; SI > 5.5, respectively) activities, suggesting the contribution of additional substances to the antiviral activity. © 2016 Wiley-VHCA AG, Zurich, Switzerland.

Anticholinergic, antihistaminic, and antiserotonergic activity of n-hexane extract of Zanthoxylum alatum seeds on isolated tissue preparations: An ex vivo study.

PubMed

Saikia, Beenita; Barua, Chandana Choudhury; Haloi, Prakash; Patowary, Pompy

2017-01-01

The aim of this study was to evaluate anticholinergic, antihistaminic, and antiserotonergic activity of the n-hexane extract of the seeds of Zanthoxylum alatum (ZAHE) on isolated ileum of rat and guinea pig and fundus of rat. ZAHE was prepared using soxhlet extraction and cumulative concentration response curves were constructed using various doses on the tissues for acetylcholine (ACh), 5-hydroxytryptamine (5-HT), and histamine with or without n-hexane extract. Atropine, ketanserin, and pheniramine maleate were used as antagonists for ACh, serotonin, and histamine, respectively. ZAHE-induced concentration-dependent inhibition of isolated ileum and fundus in rat and ileum of guinea pig. The half maximal effective concentration (EC 50 ) of ACh in the presence of atropine (10 -6 M; P < 0.05) and ZAHE (1000 μg/ml; P < 0.01) was significantly higher than EC 50 of ACh alone. The EC 50 of 5-HT in the presence of ketanserin (10 -5 M; P < 0.01) and ZAHE (1000 μg/ml; P < 0.05) was higher than EC 50 of 5-HT alone. Similarly, the EC 50 of histamine in the presence of pheniramine maleate (10 -6 M; P < 0.01) and ZAHE (300 μg/ml; P < 0.01 and 1000 μg/ml; P < 0.05) was also significantly higher than EC 50 of histamine alone. From the study, it was observed that ZAHE shows significant anticholinergic, antiserotonergic, and antihistaminic activity. The study provides sufficient evidence that the seeds can be used in gastric disorders, cough, chest infection, etc., as per folklore claims.

Investigation of the dermal sensitization potential of various essential oils in the local lymph node assay.

PubMed

Lalko, J; Api, A M

2006-05-01

Essential oils are commonly used fragrance ingredients. The oils themselves are complex mixtures, which may contain naturally occurring contact sensitizers. The local lymph node assay was used to evaluate the dermal sensitization potential of basil, citronella, clove leaf, geranium, litsea cubeba, lemongrass, and palmarosa oils. Three of the major components--citral, eugenol, and geraniol--were included to investigate any difference in sensitization potential arising from their exposure in a mixture. Each fragrance material was tested at five concentration ranging from 2.5% to 50% w/v in 1:3 ethanol:diethyl phthalate. The stimulation index (SI) values were calculated for each dose level, an SI > or = 3 was considered a positive response. The estimated concentration (EC3) required to elicit a positive was calculated and taken as a measure of relative potency. The EC3 values and potency classification for basil, clove leaf, litsea cubeba, lemongrass and palmarosa oils were calculated to be <2.5% (> or = moderate), 7.1% (weak), 8.4% (weak), 6.5% (weak) and 9.6% (weak), respectively. Citronella and geranium oils were negative. The individual components citral, eugenol and geraniol resulted in EC3 values of 6.3%, 5.4% and 11.4%, respectively. In general, the potency of each essential oil did not differ significantly from that observed for its main individual component.

Pharmacokinetics and Pharmacodynamics of (S)-Ketoprofen Co-Administered with Caffeine: A Preclinical Study in Arthritic Rats.

PubMed

Medina-López, Raúl; Vara-Gama, Nancy; Soria-Arteche, Olivia; Moreno-Rocha, Luis A; López-Muñoz, Francisco J

2018-01-26

The purpose of the present study was to determine whether caffeine modifies the pharmacokinetics and pharmacodynamics of ( S )-ketoprofen following oral administration in a gout-type pain model. 3.2 mg/kg of ( S )-ketoprofen alone and combined with 17.8 mg/kg of caffeine were administered to Wistar rats and plasma levels were determined between 0.5 and 24.0 h. Additionally, antinociception was evaluated based on the protocol of the PIFIR (pain-induced functional impairment in the rat) model before blood sampling between 0.5 and 4.0 h. Significant differences in C max , AUC 0-24 , and AUC 0-∞ values were observed with caffeine administration ( p < 0.05). Also, significant differences in E max , T max , and AUC 0-4 values were determined when comparing the treatments with and without caffeine ( p < 0.05). By relating the pharmacokinetic and pharmacodynamic data, a counter-clockwise hysteresis loop was observed regardless of the administration of caffeine. When the relationship between AUCe and AUCp was fitted to the sigmoidal E max model, a satisfactory correlation was found (R² > 0.99) as well as significant differences in E max and EC 50 values ( p < 0.05). With caffeine, E max and EC 50 values changed by 489.5% and 695.4%, respectively. The combination studied represents a convenient alternative for the treatment of pain when considering the advantages offered by using drugs with different mechanisms of action.

Pharmacokinetics and Pharmacodynamics of (S)-Ketoprofen Co-Administered with Caffeine: A Preclinical Study in Arthritic Rats

PubMed Central

Vara-Gama, Nancy; Soria-Arteche, Olivia; Moreno-Rocha, Luis A.; López-Muñoz, Francisco J.

2018-01-01

The purpose of the present study was to determine whether caffeine modifies the pharmacokinetics and pharmacodynamics of (S)-ketoprofen following oral administration in a gout-type pain model. 3.2 mg/kg of (S)-ketoprofen alone and combined with 17.8 mg/kg of caffeine were administered to Wistar rats and plasma levels were determined between 0.5 and 24.0 h. Additionally, antinociception was evaluated based on the protocol of the PIFIR (pain-induced functional impairment in the rat) model before blood sampling between 0.5 and 4.0 h. Significant differences in Cmax, AUC0-24, and AUC0-∞ values were observed with caffeine administration (p < 0.05). Also, significant differences in Emax, Tmax, and AUC0-4 values were determined when comparing the treatments with and without caffeine (p < 0.05). By relating the pharmacokinetic and pharmacodynamic data, a counter-clockwise hysteresis loop was observed regardless of the administration of caffeine. When the relationship between AUCe and AUCp was fitted to the sigmoidal Emax model, a satisfactory correlation was found (R2 > 0.99) as well as significant differences in Emax and EC50 values (p < 0.05). With caffeine, Emax and EC50 values changed by 489.5% and 695.4%, respectively. The combination studied represents a convenient alternative for the treatment of pain when considering the advantages offered by using drugs with different mechanisms of action. PMID:29373537

An evidence-based approach to the evaluation of ethnoveterinary medicines against strongyle nematodes of equids.

PubMed

Peachey, L E; Pinchbeck, G L; Matthews, J B; Burden, F A; Mulugeta, G; Scantlebury, C E; Hodgkinson, J E

2015-05-30

Cyathostomins are the most important gastrointestinal nematode infecting equids. Their effective control is currently under threat due to widespread resistance to the broad spectrum anthelmintics licenced for use in equids. In response to similar resistance issues in other helminths, there has been increasing interest in alternative control strategies, such as bioactive plant compounds derived from traditional ethnoveterinary treatments. This study used an evidence-based approach to evaluate the potential use of plant extracts from the UK and Ethiopia to treat cyathostomins. Plants were shortlisted based on findings from a literature review and additionally, in Ethiopia, the results of a participatory rural appraisal (PRA) in the Oromia region of the country. Systematic selection criteria were applied to both groups to identify five Ethiopian and four UK plants for in vitro screening. These included Acacia nilotica (L.) Delile, Cucumis prophetarum L., Rumex abyssinicus Jacq., Vernonia amygdalina Delile. and Withania somnifera (L.) Dunal from Ethiopia and Allium sativum L. (garlic), Artemisia absinthium L., Chenopodium album L. and Zingiber officinale Roscoe. (ginger) from the UK. Plant material was collected, dried and milled prior to hydro-alcoholic extraction. Crude extracts were dissolved in distilled water (dH2O) and dimethyl sulfoxide (DMSO), serially diluted and screened for anthelmintic activity in the larval migration inhibition test (LMIT) and the egg hatch test (EHT). Repeated measures ANOVA was used to identify extracts that had a significant effect on larval migration and/or egg hatch, compared to non-treated controls. The median effective concentration (EC-50) for each extract was calculated using PROBIT analysis. Of the Ethiopian extracts A. nilotica, R. abyssinicus and C. prophetarum showed significant anthelmintic activity. Their lowest EC-50 values were 0.18 (confidence interval (CI): 0.1-0.3), 1.1 (CI 0.2-2.2) and 1.1 (CI 0.9-1.4)mg/ml, respectively. All four UK extracts, A. sativum, C. album, Z. officinale and A. absinthium, showed significant anthelmintic activity. Their lowest EC-50 values were 1.1 (CI 0.9-1.3), 2.3 (CI 1.9-2.7) and 0.3 (CI 0.2-0.4)mg/ml, respectively. Extract of A. absinthium had a relatively low efficacy and the data did not accurately fit a PROBIT model for the dose response relationship, thus an EC-50 value was not calculated. Differences in efficacy for each extract were noted, dependent on the assay and solvent used, highlighting the need for a systematic approach to the evaluation of bioactive plant compounds. This study has identified bioactive plant extracts from the UK and Ethiopia which have potential as anthelmintic forages or feed supplements in equids. Copyright © 2015 Elsevier B.V. All rights reserved.

Cynodon dactylon and Sida acuta extracts impact on the function of the cardiovascular system in zebrafish embryos.

PubMed

Kannan, Rajaretinam Rajesh; Vincent, Samuel Gnana Prakash

2012-03-01

The aim of the present study was to screen cardioactive herbs from Western Ghats of India. The heart beat rate (HBR) and blood flow during systole and diastole were tested in zebrafish embryos. We found that Cynodon dactylon (C. dactylon) induced increases in the HBR in zebrafish embryos with a HBR of (3.968±0.344) beats/s, which was significantly higher than that caused by betamethosone [(3.770±0.344) beats/s]. The EC50 value of C. dactylon was 3.738 µg/mL. The methanolic extract of Sida acuta (S. acuta) led to decreases in the HBR in zebrafish embryos [(1.877±0.079) beats/s], which was greater than that caused by nebivolol (positive control). The EC50 value of Sida acuta was 1.195 µg/mL. The untreated embryos had a HBR of (2.685±0.160) beats/s at 3 d post fertilization (dpf). The velocities of blood flow during the cardiac cycle were (2,291.667±72.169) µm/s for the control, (4,250±125.000) µm/s for C. dactylon and (1,083.333±72.169) µm/s for S. acuta. The LC50 values were 32.6 µg/mL for C. dactylon and 20.9 µg/mL for S. acuta. In addition, the extracts exhibited no chemical genetic effects in the drug dosage range tested. In conclusion, we developed an assay that can measure changes in cardiac function in response to herbal small molecules and determine the cardiogenic effects by microvideography.

Toxicity assessment of a common laundry detergent using the freshwater flagellate Euglena gracilis.

PubMed

Azizullah, Azizullah; Richter, Peter; Häder, Donat-Peter

2011-09-01

Synthetic detergents are among the commonly used chemicals in everyday life. Detergents, reaching aquatic environments through domestic and municipal wastewater, can cause many different effects in aquatic organisms. The present study was aimed at the toxicity evaluation of a commonly used laundry detergent, Ariel, using the freshwater flagellate Euglena gracilis as a biotest organism. Different parameters of the flagellate like motility, swimming velocity, cell shape, gravitactic orientation, photosynthesis and concentration of light harvesting pigments were used as end points for the toxicity assessment. No Observed Effect Concentration (NOEC) and EC(50) values were calculated for the end point parameters at four different incubation times, i.e. 0, 6, 24 and 72 h. After 72 h incubation, swimming velocity of the cells was found to be the most sensitive parameter giving NOEC and EC(50) values of 10.8 and 34 mg L(-1), respectively. After 72 h exposure to the detergent, chlorophyll a and total carotenoids were significantly decreased in cultures treated with Ariel at concentrations of 50 mg L(-1) and above while chlorophyll b significantly decreased at concentrations above 750 mg L(-1). The maximum inhibitory effect on the quantum yield of photosystem II was observed after 24 h exposure and thereafter a recovery trend was observed. Motility, gravitaxis and cell shape were strongly impaired immediately upon exposure to the detergent, but with increasing exposure time these parameters showed acclimatization to the stress and thus the NOEC values obtained after 72 h were higher than those immediately after exposure. Copyright © 2011 Elsevier Ltd. All rights reserved.

Verification of quality parameters for portal images in radiotherapy.

PubMed

Pesznyák, Csilla; Polgár, István; Weisz, Csaba; Király, Réka; Zaránd, Pál

2011-03-01

The purpose of the study was to verify different values of quality parameters of portal images in radiotherapy. We investigated image qualities of different field verification systems. Four EPIDs (Siemens OptiVue500aSi(®), Siemens BeamView Plus(®), Elekta iView(®) and Varian PortalVision™) were investigated with the PTW EPID QC PHANTOM(®) and compared with two portal film systems (Kodak X-OMAT(®) cassette with Kodak X-OMAT V(®) film and Kodak EC-L Lightweight(®) cassette with Kodak Portal Localisation ReadyPack(®) film). A comparison of the f50 and f25 values of the modulation transfer functions (MTFs) belonging to each of the systems revealed that the amorphous silicon EPIDs provided a slightly better high contrast resolution than the Kodak Portal Localisation ReadyPack(®) film with the EC-L Lightweight(®) cassette. The Kodak X-OMAT V(®) film gave a poor low contrast resolution: from the existing 27 holes only 9 were detectable. On the base of physical characteristics, measured in this work, the authors suggest the use of amorphous-silicon EPIDs producing the best image quality. Parameters of the EPIDs with scanning liquid ionisation chamber (SLIC) were very stable. The disadvantage of older versions of EPIDs like SLIC and VEPID is a poor DICOM implementation, and the modulation transfer function (MTF) values (f50 and f25) are less than that of aSi detectors.

Structural characterization and evaluation of antioxidant, anticancer and hypoglycemic activity of radiation degraded oat (Avena sativa) β- glucan

NASA Astrophysics Data System (ADS)

Hussain, Peerzada R.; Rather, Sarver A.; Suradkar, Prashant P.

2018-03-01

Oat β-D-glucan after extraction was degraded at doses of 3, 6, 9, 12 and 15 kGy. The average molecular weight decreased to 45 kDa at dose of 15 kGy from an initial value of 200 kDa in native sample. XRD analysis revealed no significant change in diffraction pattern of irradiated samples when compared with control, except a decrease in intensity of x-ray diffraction. The results of the antioxidant activity revealed decrease in EC50 values and corresponding increase in antioxidant activity of radiation degraded oat β-D-glucan. Results of the anticancer studies indicated that cytotoxicity of gamma irradiated oat β-D-glucan in cancer cell lines was highest against colo-205 and MCF7 cancer cells compared to T47D cell and no cytotoxicity was observed in normal cell lines at all concentrations used. Evaluation of hypoglycemic activity showed highest inhibition in α-glucosidase activity compared to α-amylase activity due to gamma irradiation of oat β-D-glucan. Comparison of the EC50 values of known standards and gamma irradiated oat beta-glucan samples indicates that radiation treatment significantly modified the biological activity of the beta-glucan samples. Therefore, it is suggested that gamma irradiation can be used for producing low molecular weight oat β-D-glucan; which can help in modifying the biological activities.

10 CFR 39.53 - Energy compensation source.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Energy compensation source. 39.53 Section 39.53 Energy NUCLEAR REGULATORY COMMISSION LICENSES AND RADIATION SAFETY REQUIREMENTS FOR WELL LOGGING Equipment § 39.53 Energy compensation source. The licensee may use an energy compensation source (ECS) which is...

10 CFR 39.53 - Energy compensation source.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Energy compensation source. 39.53 Section 39.53 Energy NUCLEAR REGULATORY COMMISSION LICENSES AND RADIATION SAFETY REQUIREMENTS FOR WELL LOGGING Equipment § 39.53 Energy compensation source. The licensee may use an energy compensation source (ECS) which is...

10 CFR 39.53 - Energy compensation source.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Energy compensation source. 39.53 Section 39.53 Energy NUCLEAR REGULATORY COMMISSION LICENSES AND RADIATION SAFETY REQUIREMENTS FOR WELL LOGGING Equipment § 39.53 Energy compensation source. The licensee may use an energy compensation source (ECS) which is...

10 CFR 39.53 - Energy compensation source.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Energy compensation source. 39.53 Section 39.53 Energy NUCLEAR REGULATORY COMMISSION LICENSES AND RADIATION SAFETY REQUIREMENTS FOR WELL LOGGING Equipment § 39.53 Energy compensation source. The licensee may use an energy compensation source (ECS) which is...

10 CFR 39.53 - Energy compensation source.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Energy compensation source. 39.53 Section 39.53 Energy NUCLEAR REGULATORY COMMISSION LICENSES AND RADIATION SAFETY REQUIREMENTS FOR WELL LOGGING Equipment § 39.53 Energy compensation source. The licensee may use an energy compensation source (ECS) which is...

Environmental assessment of three egg production systems - Part III: Airborne bacteria concentrations and emissions.

PubMed

Zhao, Y; Zhao, D; Ma, H; Liu, K; Atilgan, A; Xin, H

2016-07-01

Airborne microorganism level is an important indoor air quality indicator, yet it has not been well documented for laying-hen houses in the United States. As a part of the Coalition for Sustainable Egg Supply (CSES) environmental monitoring project, this study comparatively monitored the concentrations and emissions of airborne total and Gram-negative (Gram(-)) bacteria in three types of commercial laying-hen houses, i.e., conventional cage (CC), aviary (AV), and enriched colony (EC) houses, over a period of eight months covering the mid and late stages of the flock cycle. It also delineated the relationship between airborne total bacteria and particulate matter smaller than 10 μm in aerodynamic diameter (PM10). The results showed airborne total bacteria concentrations (log CFU/m(3)) of 4.7 ± 0.3 in CC, 6.0 ± 0.8 in AV, and 4.8 ± 0.3 in EC, all being higher than the level recommended for human environment (3.0 log CFU/m(3)). The much higher concentrations in AV arose from the presence of floor litter and hen activities on it, as evidenced by the higher concentrations in the afternoon (with litter access) than in the morning (without litter access). The overall means and standard deviation of airborne total bacteria emission rates, in log CFU/[h-hen] (or log CFU/[h-AU], AU = animal unit or 500 kg live weight) were 4.8 ± 0.4 (or 7.3 ± 0.4) for CC, 6.1 ± 0.7 (or 8.6 ± 0.7) for AV, and 4.8 ± 0.5 (or 7.3 ± 0.5) for EC. Both concentration and emission rate of airborne total bacteria were positively related to PM10 Gram(-) bacteria were present at low concentrations in all houses; and only 2 samples (6%) in CC, 7 (22%) samples in AV, and 2 (6%) samples in EC out of 32 air samples collected in each house were found positive with Gram(-) bacteria. The concentration of airborne Gram(-) bacteria was estimated to be <2% of the total bacteria. Total bacteria counts in manure on belt (in all houses) and floor litter (only in AV) were similar; however, the manure had much more Gram(-) bacteria than the litter. The results point out the need to mitigate airborne total bacteria in laying-hen houses, especially in AV houses. © 2016 Poultry Science Association Inc.

Propofol Requirement for Induction of Unconsciousness Is Reduced in Patients with Parkinson's Disease: A Case Control Study

PubMed Central

Xu, Xiao-ping; Yu, Xi-ya; Wu, Xi; Hu, Xiao-wu; Chen, Jian-chun; Li, Jin-bao; Deng, Xiao-ming

2015-01-01

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, but whether the neurodegenerative process influences the pharmacodynamics of propofol remains unclear. We aimed to evaluate the effect of PD on pharmacodynamics of propofol. A total of 31 PD patients undergoing surgical treatment (PD group) and 31 pair-controlled non-PD patients undergoing intracranial surgery (NPD group) were recruited to investigate the propofol requirement for unconsciousness induction. Unconsciousness was induced in all patients with target-controlled infusion of propofol. The propofol concentration at which unconsciousness was induced was compared between the two groups. EC50 and EC95 were calculated as well. Demographic data, bispectral index, and hemodynamic values were comparable between PD and NPD groups. The mean target concentration of propofol when unconsciousness was achieved was 2.32 ± 0.38 μg/mL in PD group, which was significantly lower than that in NPD group (2.90 ± 0.35 μg/mL). The EC50 was 2.05 μg/mL (95% CI: 1.85–2.19 μg/mL) in PD group, much lower than the 2.72 μg/mL (95% CI: 2.53–2.88 μg/mL) in NPD group. In conclusion, the effective propofol concentration needed for induction of unconsciousness in 50% of patients is reduced in PD patients. (This trial is registered with NCT01998204.) PMID:26495319

Glyceria maxima as new test species for the EU risk assessment for herbicides: a microcosm study.

PubMed

Mohr, S; Schott, J; Hoenemann, L; Feibicke, M

2015-03-01

In its recent guidance document on tiered risk assessment for plant protection products for aquatic organisms, the European Food Safety Authority (EFSA) proposed to use Glyceria maxima as monocotyledonous grass species for the testing of special herbicide groups. However, published toxicity data for this species is very limited and there is no test guideline for Glyceria sp. For this reason a microcosm study was conducted in order to gain experience on the degree of sensitivity of G. maxima to the herbicidal substances clodinafop-propargyl (grass herbicide) and fluroxypyr (auxin) in comparison to the already established test organism water milfoil Myriophyllum spicatum and the duckweed species Landoltia punctata. Five concentrations without replicates were tested for each test substance using 10 microcosms and three microcosms served as controls. The experiment was run for 8 weeks. Morphological endpoints were used to determine growth and EC50 values. The results show that M. spicatum was most sensitive to fluroxypyr (37 days EC50 for roots: 62 µg/L) and G. maxima most sensitive to clodinafop-propargyl (22 days EC50 for total shoot length: 48 µg/L) whereas the duckweed species was considerable less sensitive. Hence, G. maxima turns out to be a good candidate for testing grass specific herbicides, supporting its inclusion as an additional macrophyte test for the risk assessment of herbicides as proposed by the EFSA.

Synergistic antinociceptive interaction between palmitoylethanolamide and tramadol in the mouse formalin test.

PubMed

Déciga-Campos, Myrna; Ramírez-Marín, Pamela Moncerrat; López-Muñoz, Francisco Javier

2015-10-15

Pharmacological synergism has been used to obtain a higher efficacy using drug concentrations at which side effects are minimal. In this study, the pharmacological antinociceptive interaction between N-palmitoylethanolamide (PEA) and tramadol was investigated. The individual concentration-response curves for PEA (0.1-56.2 μg/paw) and tramadol (1-56.2 μg/paw) were evaluated in mice in which nociception was induced by an intraplantar injection of 2% formalin. Isobolographic analysis was used to evaluate the pharmacological interaction between PEA (EC50=23.7±1.6 μg/paw) and tramadol (EC50=26.02±2.96 μg/paw) using the EC50 and a fixed 1:1 ratio combination. The isobologram demonstrated that the combinations investigated in this study produced a synergistic interaction; the experimental values (Zexp=9.5±0.2 μg/paw) were significantly smaller than those calculated theoretically (Zadd=24.8±0.2 μg/paw). The antinociceptive mechanisms of the PEA and tramadol combination involved the opioid receptor, transient receptor potential cation channel subfamily V member 1 (TRPV1), and peroxisome proliferator-activated receptor alpha (PPAR-α). The sedative effect of the combination of PEA and tramadol was less than that generated by individual treatments. These findings suggest that the PEA and tramadol combination produced enhanced antinociceptive efficacy at concentrations at which side effects are minimal. Copyright © 2015 Elsevier B.V. All rights reserved.

Health-Promoting Effects of Thymus herba-barona, Thymus pseudolanuginosus, and Thymus caespititius Decoctions

PubMed Central

Afonso, Andrea F.; Pereira, Olívia R.; Neto, Rodrigo T.

2017-01-01

Thymus herba-barona, Thymus pseudolanuginosus, and Thymus caespititius decoctions were screened for their phenolic constituents, along with their potential antioxidant, anti-inflammatory, and antibacterial activities. The total phenolic compounds in the extracts of the three plants ranged from 236.0 ± 26.6 mgGAE/g (T. caespititus) to 293.0 ± 30.5 mgGAE/g of extract (T. pseudolanuginosus), being particularly rich in caffeic acid derivatives, namely rosmarinic acid and its structural isomers, as well as flavones, such as luteolin-O-glucuronide. The T. pseudolanuginosus extract presented the best DPPH radical scavenging ability (EC50 = 10.9 ± 0.7 µg/mL), a high reducing power (EC50 = 32.2 ± 8.2 µg/mL), and effectively inhibited the oxidation of β-carotene (EC50 = 2.4 ± 0.2 µg/mL). The extracts also showed NO● scavenging activity close to that of ascorbic acid, and thus might be useful as anti-inflammatory agents. In addition, they exhibited antibacterial activity against gram-negative and gram-positive bacteria. Staphylococcus aureus strains were the most sensitive bacteria to thyme extracts, with minimum inhibitory concentration and minimum bactericidal concentration values in the range of 0.6–3.5 mg/mL. Overall, this work is an important contribution for the phytochemical characterization and the potential antioxidant, anti-inflammatory, and antimicrobial activities of these three Thymus species, which have been poorly explored. PMID:28858228

Matrix Extension Study: Validation of the Compact Dry EC Method for Enumeration of Escherichia coli and non-E. coli Coliform Bacteria in Selected Foods.

PubMed

Mizuochi, Shingo; Nelson, Maria; Baylis, Chris; Green, Becky; Jewell, Keith; Monadjemi, Farinaz; Chen, Yi; Salfinger, Yvonne; Fernandez, Maria Cristina

2016-01-01

The Compact Dry "Nissui" EC method, originally certified by the AOAC Research Institute Performance Test Method(SM) program for enumeration of Escherichia coli and non-E. coli coliforms in raw meat products (Performance Tested Method(SM) 110402), has undergone an evaluation to extend the method's claim to cooked chicken, prewashed bagged shredded iceberg lettuce, frozen cod filets, instant nonfat dry milk powder, and pasteurized milk (2% fat). Compact Dry EC is a ready-to-use dry media sheet containing a cold-soluble gelling agent, selective agents, and a chromogenic medium, which are rehydrated by adding 1 mL diluted sample. E. coli form blue/blue-purple colonies, whereas other coliform bacteria form red/pink colonies. Users can obtain an E. coli count (blue/blue-purple colonies only) and a total coliform count (red/pink plus blue/blue-purple colonies) after 24 ± 2 h of incubation at 37 ± 1°C. The matrix extension study was organized by Campden BRI (formerly Campden and Chorleywood Food Research Association Technology, Ltd), Chipping Campden, United Kingdom. Method comparison data for cooked chicken, prewashed bagged shredded iceberg lettuce, frozen cod filets, and instant nonfat dry milk powder were collected in a single-laboratory evaluation by Campden BRI. A multilaboratory study was conducted on pasteurized milk (2% fat), with 13 laboratories participating. The Compact Dry EC method was compared to ISO 16649-2:2001 "Microbiology of food and animal feeding stuffs-Horizontal method for the enumeration of beta-glucuronidase-positive Escherichia coli-Part 2: Colony-count technique at 44 degrees C using 5-bromo-4-chloro-3-indolyl beta-D-glucuronide" and to ISO 4832:2006 "Microbiology of food and animal feeding stuffs-Horizontal method for the enumeration of coliforms-Colony-count technique," the current standards at the time of this study. Each matrix was evaluated separately for E. coli and non-E. coli coliforms at each contamination level (including an uncontaminated level). In the single-laboratory evaluation (cooked chicken, prewashed bagged shredded iceberg lettuce, frozen cod filets, and instant nonfat dry milk powder), colony counts were logarithmically transformed, and then the data were analyzed at each level for sr, RSDr, and mean difference between methods with 95% confidence intervals (CIs). A CI outside a range of -0.5 to 0.5 on the log10 mean difference between methods was used as the criterion to establish a significant statistical difference. In the multilaboratory study on pasteurized milk, after logarithmic transformation, the data were analyzed for sR and RSDR in addition to sr, RSDr, and mean difference with 95% CIs. Regression analysis was performed on all matrixes and reported as r(2). In the single-laboratory evaluation, statistical differences were indicated between the Compact Dry EC and ISO 16649-2 methods for the enumeration of E. coli in two of five contamination levels tested for lettuce, and in the low contamination level for cooked chicken. For the cooked chicken and lettuce at the low level, only a few colonies were recovered for each method, and thus not a true indication of the methods' performance. For the high contamination level of lettuce, counts varied within the sets of five replicates more than 10-fold for each method, which may have contributed to the significant difference. Statistical differences were also indicated between the Compact Dry EC and ISO 4832 methods for the enumeration of coliforms in two of five contamination levels tested for lettuce, two of five contamination levels of milk powder, and in the low contamination level for frozen fish. For the lowest levels of frozen fish and milk powder, only a few colonies were recovered for each method. For the lettuce and the other level of milk powder, counts varied within the sets of five replicates more than 10-fold for each method, which may have contributed to the significant differences indicated in the those contamination levels. In most cases, mean differences between the Compact Dry EC and International Organization of Standardization (ISO) methods were well below 0.5 log10, and the CIs were within the acceptance criterion (-0.5 to 0.5). The sr and RSDr values were similar for both methods, and r(2) values were >0.92 for all comparisons. In the multilaboratory study, no statistical differences were indicated between the methods. The sr, RSDr, sR, and RSDr values were similar for each method and even slightly smaller in most cases for the Compact Dry EC. The r(2) value was 0.97 in comparison to ISO 16649-2, and 0.99 in comparison to ISO 4832. The Compact Dry EC offers comparable results to the ISO standard plating methods in a space saving, easy-to-use format.

The effect of isoenzyme-selective PDE inhibitors on methacholine-induced contraction of guinea-pig and rat ileum.

PubMed Central

Tomkinson, A.; Raeburn, D.

1996-01-01

1. We have examined the effects of the isoenzyme-selective phosphodiesterase (PDE) inhibitors, vinpocetine (type 1), siguazodan (type 3), rolipram (type 4) and zaprinast (type 5) and the non-selective PDE inhibitor enprofylline on methacholine (MCh) contractile concentration-response curves on guinea-pig and rat isolated ileum. 2. In guinea-pig ileum, vinpocetine (10-300 microM), zaprinast (1-300 microM) and enprofylline (100-1000 microM) produced a concentration-dependent depression of the maximum response (Emax) to MCh only without effect on the MCh EC50 values (rank order of potency: zaprinast > vinpocetine > enprofylline). In contrast, siguazodan (10-300 microM) and rolipram (10-300 microM) produced a rightward displacement of the MCh concentration-response curve (increase in EC50: rank order; rolipram > siguazodan), with effects on the MCh maximum seen only at higher concentrations. 3. In the rat ileum, vinpocetine (10-300 microM), zaprinast (0.1-300 microM) and enprofylline (100-1000 microM) caused depression of the MCh maximum contraction (rank order: zaprinast > vinpocetine > enprofylline). Low concentrations of rolipram and siguazodan had no significant effect on the MCh maximum. In the presence of higher concentrations (> 100 microM) of rolipram and siguazodan, a maximum response was not achieved at the highest concentration of MCh tested. As in the guinea-pig ileum, only rolipram (10-300 microM) and siguazodan (10-300 microM) produced a significant, concentration-dependent, rightward displacement of the MCh concentration-response curve (increase in EC50: rank order: rolipram > siguazodan). 4. In the guinea-pig ileum, isoprenaline (0.1 microM) produced a rightward displacement (approximately 3 fold) of the MCh concentration-response curve, accompanied by a significant depression of the maximum response. Increasing the isoprenaline concentration (1 microM) had no further effect on either parameter. Sodium nitroprusside (SNP, > or = 10 microM) produced a concentration-dependent depression of the MCh maximum without an effect on the EC50. 5. In the rat ileum, isoprenaline (1 microM) produced a concentration-dependent rightward displacement (approximately 2.8 fold) of the MCh concentration-response curve with depression of the MCh maximum at higher (> or = 100 microM) concentrations. SNP produced depression of the MCh maximum at a concentration of 10 microM and above. Effects on the MCh EC50 were seen only at 100 and 300 microM. 6. In guinea-pig ileum, isoprenaline (0.1 microM) in combination with rolipram (10 microM) further increased the MCh EC50 and reduced the MCh maximum. The combination of SNP (10 microM) with zaprinast (0.1 microM) produced no further significant effect than SNP alone. 7. In rat ileum, isoprenaline (1 microM) in combination with rolipram (10 microM) further increased the EC50 and reduced the maximum. SNP (10 microM) had no significant effect on either the MCh maximum or EC50. A combination with zaprinast (1 microM) had no further effect. 8. In conclusion, all the PDE inhibitors tested produced a concentration-dependent inhibition of the MCh concentration-response curve, indicating a modulator role for the PDE isoenzymes in gastrointestinal smooth muscle contractility. The PDE inhibitors that elevate cyclic GMP produced a depression of the MCh maximum response only, whilst those that elevate cyclic AMP produced a rightward displacement of the MCh concentration-response curve. This was confirmed by the use of isoprenaline and SNP. This difference in the type of inhibition produced by these PDE isoenzyme inhibitors may reflect a different intracellular site/mechanism by which the cyclic AMP- and cyclic GMP-activated kinases act functionally to antagonize the contractile response. PMID:8864552

Study of the partition coefficients Kp/f of seven model migrants from LDPE polymer in contact with food simulants.

PubMed

Paseiro-Cerrato, Rafael; Tongchat, Chinawat; Franz, Roland

2016-05-01

This study evaluated the influence of parameters such as temperature and type of low-density polyethylene (LDPE) film on the log Kp/f values of seven model migrants in food simulants. Two different types of LDPE films contaminated by extrusion and immersion were placed in contact with three food simulants including 20% ethanol, 50% ethanol and olive oil under several time-temperature conditions. Results suggest that most log Kp/f values are little affected by these parameters in this study. In addition, the relation between log Kp/f and log Po/w was established for each food simulant and regression lines, as well as correlation coefficients, were calculated. Correlations were compared with data from real foodstuffs. Data presented in this study could be valuable in assigning certain foods to particular food simulants as well as predicting the mass transfer of potential migrants into different types of food or food simulants, avoiding tedious and expensive laboratory analysis. The results could be especially useful for regulatory agencies as well as for the food industry.

Retinal nerve fiber layer thickness analysis in suspected malingerers with optic disc temporal pallor

PubMed Central

Civelekler, Mustafa; Halili, Ismail; Gundogan, Faith C; Sobaci, Gungor

2009-01-01

Purpose: To investigate the value of temporal retinal nerve fiber layer (RNFLtemporal) thickness in the prediction of malingering. Materials and Methods: This prospective, cross-sectional study was conducted on 33 military conscripts with optic disc temporal pallor (ODTP) and 33 age-and sex-matched healthy controls. Initial visual acuity (VAi) and visual acuity after simulation examination techniques (VAaset) were assessed. The subjects whose VAaset were two or more lines higher than VAi were determined as malingerers. Thickness of the peripapillary RNFL was determined with OCT (Stratus OCT™, Carl Zeiss Meditec, Inc.). RNFLtemporal thickness of the subjects were categorized into one of the 1+ to 4+ groups according to 50% confidence interval (CI), 25% CI and 5% CI values which were assessed in the control group. The VAs were converted to LogMAR-VAs for statistical comparisons. Results: A significant difference was found only in the temporal quadrant of RNFL thickness in subjects with ODTP (P=0.002). Mean LogMAR-VA increased significantly after SETs (P<0.001). Sensitivity, specificity, positive and negative predictive values of categorized RNFLtemporal thickness in diagnosing malingering were 84.6%, 75.0%, 68.8%, 88.2%, respectively. ROC curve showed that RNFLtemporal thickness of 67.5 μm is a significant cut-off point in determining malingering (P=0.001, area under the curve:0.862). The correlations between LogMAR-VAs and RNFLtemporal thicknesses were significant; the correlation coefficient for LogMAR-VAi was lower than the correlation for LogMAR-VAaset (r=−0.447, P=0.009 for LogMAR-VAi; r=−0.676, P<0.001 for LogMAR-VAaset). Conclusions: RNFLtemporal thickness assessment may be a valuable tool in determining malingering in subjects with ODTP objectively. PMID:19700875

Computed tomography detection of extracapsular spread of squamous cell carcinoma of the head and neck in metastatic cervical lymph nodes.

PubMed

Carlton, Joshua A; Maxwell, Adam W; Bauer, Lyndsey B; McElroy, Sara M; Layfield, Lester J; Ahsan, Humera; Agarwal, Ajay

2017-06-01

Background and purpose In patients with squamous cell carcinoma of the head and neck (HNSCC), extracapsular spread (ECS) of metastases in cervical lymph nodes affects prognosis and therapy. We assessed the accuracy of intravenous contrast-enhanced computed tomography (CT) and the utility of imaging criteria for preoperative detection of ECS in metastatic cervical lymph nodes in patients with HNSCC. Materials and methods Preoperative intravenous contrast-enhanced neck CT images of 93 patients with histopathological HNSCC metastatic nodes were retrospectively assessed by two neuroradiologists for ECS status and ECS imaging criteria. Radiological assessments were compared with histopathological assessments of neck dissection specimens, and interobserver agreement of ECS status and ECS imaging criteria were measured. Results Sensitivity, specificity, positive predictive value, and accuracy for overall ECS assessment were 57%, 81%, 82% and 67% for observer 1, and 66%, 76%, 80% and 70% for observer 2, respectively. Correlating three or more ECS imaging criteria with histopathological ECS increased specificity and positive predictive value, but decreased sensitivity and accuracy. Interobserver agreement for overall ECS assessment demonstrated a kappa of 0.59. Central necrosis had the highest kappa of 0.74. Conclusion CT has moderate specificity for ECS assessment in HNSCC metastatic cervical nodes. Identifying three or more ECS imaging criteria raises specificity and positive predictive value, therefore preoperative identification of multiple criteria may be clinically useful. Interobserver agreement is moderate for overall ECS assessment, substantial for central necrosis. Other ECS CT criteria had moderate agreement at best and therefore should not be used individually as criteria for detecting ECS by CT.

Microbiology of broiler carcasses and chemistry of chiller water as affected by water reuse.

PubMed

Northcutt, J K; Smith, D; Huezo, R I; Ingram, K D

2008-07-01

A study was conducted to determine the effects of treating and reusing poultry chiller water in a commercial poultry processing facility. Broiler carcasses and chiller water were obtained from a commercial processing facility which had recently installed a TOMCO Pathogen Management System to recycle water in sections 2 and 3 of two 3-compartment chillers. In this system, reused water is blended with fresh water to maintain the chiller volume. Carcasses were sampled prechill and postchill (final exit), and chiller water was sampled from the beginning and end of each of the 3 sections. Carcasses were subjected to a whole carcass rinse (WCR) in 0.1% peptone. Numbers of Escherichia coli (EC), coliforms (CF), and Campylobacter (CPY) were determined from the WCR and chiller water samples. Prevalence of Salmonella (SAL) was also determined on the WCR and chiller water samples. On average, prechill levels of bacteria recovered from rinses were 2.6, 2.9, and 2.6 log10 cfu/mL for EC, CF, and CPY, respectively. Ten out of 40 (25%) prechill carcasses were positive for SAL. After chilling, numbers of EC, CF, and CPY recovered from carcass rinses decreased by 1.5, 1.5, and 2.0 log10 cfu/mL, respectively. However, 9 out of 40 (22%) postchill carcasses were positive for SAL. When the chiller water samples were tested, counts of EC, CF, and CPY were found only in water collected from the first section of the chiller (inlet and outlet). Two of 4 water samples collected from the inlet of the first section tested positive for SAL. This study shows that fresh and reused water can be used to cool poultry in chiller systems to achieve a reduction in numbers of bacteria (EC, CF, and CPY) or equivalent prevalence (SAL) of bacteria recovered from broiler carcasses.

Biochemical characterization of L-asparaginase in NaCl-tolerant Staphylococcus sp. OJ82 isolated from fermented seafood.

PubMed

Han, Sangwon; Jung, Jaejoon; Park, Woojun

2014-08-01

L-Asparaginase from gram-positive bacteria has been poorly explored. We conducted recombinant overexpression and purification of L-asparaginase from Staphylococcus sp. OJ82 (SoAsn) isolated from Korean fermented seafood to evaluate its biotechnological potential as an antileukemic agent. SoAsn was expressed in Escherichia coli BL21 (DE3) with an estimated molecular mass of 37.5 kDa, determined using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Consistent with asparaginases in gram-negative bacteria, size-exclusion chromatography determined SoAsn as a homodimer. Interestingly, the optimal temperature of SoAsn was 37°C and over 90% of activity was retained between 37°C and 50°C, and its thermal stability range was narrower than that of commercial E. coli L-asparaginase (EcAsn). Both SoAsn and EcAsn were active between pH 9 and 10, although their overall pH-dependent enzyme activities were slightly different. The Km value of SoAsn was 2.2 mM, which is higher than that of EcAsn. Among eight metals tested for enzyme activity, cobalt and magnesium greatly enhanced the SoAsn and EcAsn activity, respectively. Interestingly, SoAsn retained more than 60% of its activity under 2 M NaCl condition, but the activity of EcAsn was reduced to 48%. Overall, the biochemical characteristics of SoAsn were similar to those of EcAsn, but its kinetics, cofactor requirements, and NaCl tolerance differed from those of EcAsn.

Multigeneration toxicity of imidacloprid and thiacloprid to Folsomia candida.

PubMed

van Gestel, Cornelis A M; de Lima E Silva, Claudia; Lam, Thao; Koekkoek, Jacco C; Lamoree, Marja H; Verweij, Rudo A

2017-04-01

In a recent study, we showed that the springtail Folsomia candida was quite sensitive the neonicotinoid insecticides imidacloprid and thiacloprid. This study aimed at determining the toxicity of both compounds to F. candida following exposure over three generations, in natural LUFA 2.2 standard soil. In the first generation, imidacloprid was more toxic than thiacloprid, with LC 50 s of 0.44 and 9.0 mg/kg dry soil, respectively and EC 50 s of 0.29 and 1.5 mg/kg dry soil, respectively. The higher LC 50 /EC 50 ratio suggests that thiacloprid has more effects on reproduction, while imidacloprid shows lethal toxicity to the springtails. In the multigeneration tests, using soil spiked at the start of the first generation exposures, imidacloprid had a consistent effect on survival and reproduction in all three generations, with LC 50 s and EC 50 s of 0.21-0.44 and 0.12-0.29 mg/kg dry soil, respectively, while thiacloprid-exposed animals showed clear recovery in the second and third generations (LC 50 and EC 50  > 3.33 mg/kg dry soil). The latter finding is in agreement with the persistence of imidacloprid and the fast degradation of thiacloprid in the test soil.

Identification of Leishmania donovani Topoisomerase 1 inhibitors via intuitive scaffold hopping and bioisosteric modification of known Top 1 inhibitors

NASA Astrophysics Data System (ADS)

Mamidala, Rajinikanth; Majumdar, Papiya; Jha, Kunal Kumar; Bathula, Chandramohan; Agarwal, Rahul; Chary, M. Thirumala; Mazumdar, H. K.; Munshi, Parthapratim; Sen, Subhabrata

2016-05-01

A library of arylidenefuropyridinediones was discovered as potent inhibitors of Leishmania donovani Topoisomerase 1 (LdTop1) where the active molecules displayed considerable inhibition with single digit micromolar EC50 values. This molecular library was designed via intuitive scaffold hopping and bioisosteric modification of known topoisomerase 1 inhibitors such as camptothecin, edotecarin and etc. The design was rationalized by molecular docking analysis of the compound prototype with human topoisomerase 1 (HTop1) and Leishmania donovani topoisomerase 1(LdTop1). The most active compound 4 displayed no cytotoxicity against normal mammalian COS7 cell line (~100 fold less inhibition at the EC50). Similar to camptothecin, 4 interacted with free LdTop1 as observed in the preincubation DNA relaxation inhibition experiment. It also displayed anti-protozoal activity against Leishmania donovani promastigote. Crystal structure investigation of 4 and its molecular modelling with LdTop1 revealed putative binding sites in the enzyme that could be harnessed to generate molecules with better potency.

Estimating sensible heat flux in agricultural screenhouses by the flux-variance and half-order time derivative methods

NASA Astrophysics Data System (ADS)

Achiman, Ori; Mekhmandarov, Yonatan; Pirkner, Moran; Tanny, Josef

2016-04-01

Previous studies have established that the eddy covariance (EC) technique is reliable for whole canopy flux measurements in agricultural crops covered by porous screens, i.e., screenhouses. Nevertheless, the eddy covariance technique remains difficult to apply in the farm due to costs, operational complexity, and post-processing of data - thereby inviting alternative techniques to be developed. The subject of this research was estimating the sensible heat flux by two turbulent transport techniques, namely, Flux-Variance (FV) and Half-order Time Derivative (HTD) whose instrumentation needs and operational demands are not as elaborate as the EC. The FV is based on the standard deviation of high frequency temperature measurements and a similarity constant CT. The HTD method requires mean air temperature and air velocity data. Measurements were carried out in two types of screenhouses: (i) a banana plantation in a light shading (8%) screenhouse; (ii) a pepper crop in a dense insect-proof (50-mesh) screenhouse. In each screenhouse an EC system was deployed for reference and high frequency air temperature measurements were conducted using miniature thermocouples installed at several levels to identify the optimal measurement height. Quality control analysis showed that turbulence development and flow stationarity conditions in the two structures were suitable for flux measurements by the EC technique. Energy balance closure slopes in the two screenhouses were larger than 0.71, in agreement with results for open fields. Regressions between sensible heat flux measured by EC and estimated by FV resulted with CT values that were usually larger than 1, the typical value for open field. In both shading and insect-proof screenhouses the CT value generally increased with height. The optimal measurement height, defined as the height with maximum R2 of the regression between EC and FV sensible heat fluxes, was just above the screen. CT value at optimal height was 2.64 and 1.52 for the shading and insect-proof screenhouses, respectively, with R2 = 0.73 in both types of structures. FV data analysis of the temperature signal at frequencies lower than 10 Hz showed that R2 of these regressions was insensitive to the data analysis frequency up to 0.5 Hz. This suggests that turbulent transport in the screenhouses was governed by large scale vortices. Regressions between EC and HTD sensible heat fluxes resulted with R2 which slightly decreased with height and had values between 0.3 and 0.4 for both screenhouses. The regression slopes also decreased with height and had values between 0.4 and 0.6. We conclude that in screenhouses the FV technique provides a more reliable estimate of the sensible heat flux than the HTD; however, the latter is simpler and more robust in terms of equipment, operation and data analysis and hence may be more attainable for day-to-day use by the growers.

Anticholinergic, antihistaminic, and antiserotonergic activity of n-hexane extract of Zanthoxylum alatum seeds on isolated tissue preparations: An ex vivo study

PubMed Central

Saikia, Beenita; Barua, Chandana Choudhury; Haloi, Prakash; Patowary, Pompy

2017-01-01

Objectives: The aim of this study was to evaluate anticholinergic, antihistaminic, and antiserotonergic activity of the n-hexane extract of the seeds of Zanthoxylum alatum (ZAHE) on isolated ileum of rat and guinea pig and fundus of rat. Materials and Methods: ZAHE was prepared using soxhlet extraction and cumulative concentration response curves were constructed using various doses on the tissues for acetylcholine (ACh), 5-hydroxytryptamine (5-HT), and histamine with or without n-hexane extract. Atropine, ketanserin, and pheniramine maleate were used as antagonists for ACh, serotonin, and histamine, respectively. Results: ZAHE-induced concentration-dependent inhibition of isolated ileum and fundus in rat and ileum of guinea pig. The half maximal effective concentration (EC50) of ACh in the presence of atropine (10−6 M; P < 0.05) and ZAHE (1000 μg/ml; P < 0.01) was significantly higher than EC50of ACh alone. The EC50of 5-HT in the presence of ketanserin (10−5 M; P < 0.01) and ZAHE (1000 μg/ml; P < 0.05) was higher than EC50of 5-HT alone. Similarly, the EC50of histamine in the presence of pheniramine maleate (10−6 M; P < 0.01) and ZAHE (300 μg/ml; P < 0.01 and 1000 μg/ml; P < 0.05) was also significantly higher than EC50of histamine alone. Conclusion: From the study, it was observed that ZAHE shows significant anticholinergic, antiserotonergic, and antihistaminic activity. The study provides sufficient evidence that the seeds can be used in gastric disorders, cough, chest infection, etc., as per folklore claims. PMID:28458421

Modeled dosage-response relationship on the net photosynthetic rate for the sensitivity to acid rain of 21 plant species.

PubMed

Deng, Shihuai; Gou, Shuzhen; Sun, Baiye; Lv, Wenlin; Li, Yuanwei; Peng, Hong; Xiao, Hong; Yang, Gang; Wang, Yingjun

2012-08-01

This study investigated the sensitivity of plant species to acid rain based on the modeled dosage-response relationship on the net photosynthetic rate (P (N)) of 21 types of plant species, subjected to the exposure of simulated acid rain (SAR) for 5 times during a period of 50 days. Variable responses of P (N) to SAR occurred depending on the type of plant. A majority (13 species) of the dosage-response relationship could be described by an S-shaped curve and be fitted with the Boltzmann model. Model fitting allowed quantitative evaluation of the dosage-response relationship and an accurate estimation of the EC(10), termed as the pH of the acid rain resulting in a P (N) 10 % lower than the reference value. The top 9 species (Camellia sasanqua, Cinnamomum camphora, etc. EC(10) ≤ 3.0) are highly endurable to very acid rain. The rare, relict plant Metasequoia glyptostroboides was the most sensitive species (EC(10) = 5.1) recommended for protection.

Efficacy ranking of triterpenoids as inducers of a cytoprotective enzyme and as inhibitors of a cellular inflammatory response via their electron affinity and their electrophilicity index

PubMed Central

Bensasson, René V.; Zoete, Vincent; Berthier, Gaston; Talalay, Paul; Dinkova-Kostova, Albena T.

2010-01-01

Electron affinity (EA) and electrophilicity index (ω) of 16 synthetic triterpenoids (TP), previously identified as inducers of cytoprotective enzymes and as inhibitors of cellular inflammatory responses, have been calculated by the molecular orbital method. Linear correlations were obtained by plotting the values of EA, as well as those of ω versus (i) the potencies of induction of NAD(P)H quinone reductase (NQO1, EC 1.6.99.2), a cytoprotective enzyme, expressed via the concentration of TP required to double the specific activity of NQO1 (CD value) and (ii) the values of their anti-inflammatory activity expressed via the IC-50 of TP for suppression of upregulation of inducible nitric oxide synthase (iNOS, EC 1.14.13.39), both previously experimentally determined. The observed correlations demonstrate quantitatively for a series of triterpenoids that their electrophilicity is a major factor determining their potency as inducers of the cytoprotective phase 2 response and as inhibitors of inflammatory processes. PMID:20433811

Sensitivity of spore germination and germ tube elongation of Saccharina japonica to metal exposure.

PubMed

Han, Taejun; Kong, Jeong-Ae; Kang, Hee-Gyu; Kim, Seon-Jin; Jin, Gyo-Sun; Choi, Hoon; Brown, Murray T

2011-11-01

The sensitivity of early life stages of the brown seaweed Saccharina japonica to six metals (Cd, Cu, Hg, Ni, Pb, Zn) and two waste-water samples were investigated and a new toxicity bioassay developed. The two endpoints used were spore germination and germ tube elongation with an exposure time of 24 h. Optimal test conditions determined for photon irradiance, pH, salinity and temperature were darkness, pH 8, 35‰ and 15°C, respectively. The toxicity ranking of five metals was: Hg (EC(50) of 41 and 42 μg l(-1)) > Cu (120 and 81 μg l(-1)) > Ni (2,009 and 1,360 μg l(-1)) > Zn (3,024 and 3,897 μg l(-1)) > Pb (4,760 and 4,429 μg l(-1)) > Cd (15,052 and 7,541 μg l(-1)) for germination and germ tube elongation, respectively. The sensitivities to Cd, Cu and Ni were greater in germ tube elongation than in germination process. When tested against two different waste-water samples (processed animal and printed circuit board waste-water) values of EC(50) were between 21.29 and 32.02% for germination and between 5.33 and 8.98% for germ tube elongation. Despite differences in their chemical composition, the toxic effects of waste-water samples, as indicated by EC(50) values, did not differ significantly for the same endpoints. The CV range for both germination and germ tube elongation was between 4.61 and 37.69%, indicating high levels of precision of the tests. The results compare favourably with those from more established test procedures employing micro- and macroalgae. The advantages and potential limitations of the bioassay for the assessment of anthropogenic impacts on coastal ecosystems and commercial cultivation areas in near-shore environments are discussed.

In Vitro Antiplasmodial Activities and Synergistic Combinations of Differential Solvent Extracts of the Polyherbal Product, Nefang

PubMed Central

Arrey Tarkang, Protus; Franzoi, Kathrin Diehl; Lee, Eunyoung; Freitas-Junior, Lucio; Liuzzi, Michel; Nolé, Tsabang; Ayong, Lawrence S.; Agbor, Gabriel A.; Okalebo, Faith A.; Guantai, Anastasia N.

2014-01-01

Nefang, a polyherbal product composed of Mangifera indica (bark and leaf), Psidium guajava, Carica papaya, Cymbopogon citratus, Citrus sinensis, and Ocimum gratissimum (leaves), is a potential therapy against P. falciparum malaria. In vitro antiplasmodial activities of its constituent solvent extracts were analyzed on CQ-sensitive (3D7) and multidrug resistant (Dd2) P. falciparum strains. The interactions involving the differential solvent extracts were further analyzed using a variable potency ratio drug combination approach. Effective concentration 50 (EC50) values were determined by nonlinear regression curve-fitting of the dose-response data and used in calculating the fractional inhibitory concentration 50 (FIC50) and combination indices (CI) for each pair. The derived EC50 values (3D7/Dd2, μg/mL) are Nefang-96.96/55.08, MiB-65.33/34.58, MiL-82.56/40.04, Pg-47.02/25.79, Cp-1188/317.5, Cc-723.3/141, Cs-184.4/105.1, and Og-778.5/118.9. Synergism was obtained with MiB/Pg (CI = 0.351), MiL/Pg (0.358), MiB/Cs (0.366), MiL/Cs (0.482), Pg/Cs (0.483), and Cs/Og (0.414) when analyzed at equipotency ratios. Cytotoxicity testing of Nefang and the solvent extracts on two human cell lines (Hep G2 and U2OS) revealed no significant toxicity relative to their antiplasmodial activities (SI > 20). Taken together, our data confirm the antimalarial activities of Nefang and its constituent plant extracts and identified extract pairs with promising synergistic interactions for exploitation towards a rational phytotherapeutic and evidence-based antimalarial drug discovery. PMID:24877138

Evaluation of the hydrometer for testing immunoglobulin G1 concentrations in Holstein colostrum.

PubMed

Pritchett, L C; Gay, C C; Hancock, D D; Besser, T E

1994-06-01

Hydrometer measurement in globulin and IgG1 concentration measured by the radial immunodiffusion technique were compared for 915 samples of first milking colostrum from Holstein cows. Least squares analysis of the relationship between hydrometer measurement and IgG1 concentration was improved by log transformation of IgG1 concentration and resulted in a significant linear relationship between hydrometer measurement and log10 IgG1 concentration; r2 = .469. At 50 mg of globulin/ml of colostrum, the recommended hydrometer cutoff point for colostrum selection, the sensitivity of the hydrometer as a test of IgG1 concentration in Holstein colostrum was 26%, and the negative predictive value was 67%. The negative predictive value and sensitivity of the hydrometer as a test of IgG1 in Holstein colostrum was improved, and the cost of misclassification of colostrum was minimized, when the cutoff point for colostrum selection was increased above the recommended 50 mg/ml.

Effects of Sludge Compost on EC value of Saline Soil and Plant Height of Medicago

NASA Astrophysics Data System (ADS)

Sun, Chongyang; Zhao, Ke; Chen, Xing; Wang, Xiaohui

2017-12-01

In this study, the effects of sludge composting on the EC value of saline soil and the response to Medicago plant height were studied by planting Medicago with pots for 45 days in different proportions as sludge composting with saline soil. The results showed that the EC value of saline soil did not change obviously with the increase of fertilization ratio,which indicated that the EC value of saline soil was close to that of the original soil. The EC decreased by 31.45% at fertilization ratio of 40%. The height of Medicago reached the highest at 40% fertilization ratio, and that was close to 60% fertilization ratio, and the difference was significant with other treatments. By comprehensive analyse and compare,the optimum application rate of sludge compost was 40% under this test condition.

Ecotoxicology of bromoacetic acid on estuarine phytoplankton.

PubMed

Gordon, Ana R; Richardson, Tammi L; Pinckney, James L

2015-11-01

Bromoacetic acid is formed when effluent containing chlorine residuals react with humics in natural waters containing bromide. The objective of this research was to quantify the effects of bromoacetic acid on estuarine phytoplankton as a proxy for ecosystem productivity. Bioassays were used to measure the EC50 for growth in cultured species and natural marine communities. Growth inhibition was estimated by changes in chlorophyll a concentrations measured by fluorometry and HPLC. The EC50s for cultured Thalassiosira pseudonana were 194 mg L(-1), 240 mg L(-1) for Dunaliella tertiolecta and 209 mg L(-1) for Rhodomonas salina. Natural phytoplankton communities were more sensitive to contamination with an EC50 of 80 mg L(-1). Discriminant analysis suggested that bromoacetic acid additions cause an alteration of phytoplankton community structure with implications for higher trophic levels. A two-fold EC50 decrease in mixed natural phytoplankton populations affirms the importance of field confirmation for establishing water quality criteria. Copyright © 2015 Elsevier Ltd. All rights reserved.

Probabilistic risk assessment of the effect of acidified seawater on development stages of sea urchin (Strongylocentrotus droebachiensis).

PubMed

Chen, Wei-Yu; Lin, Hsing-Chieh

2018-05-01

Growing evidence indicates that ocean acidification has a significant impact on calcifying marine organisms. However, there is a lack of exposure risk assessments for aquatic organisms under future environmentally relevant ocean acidification scenarios. The objective of this study was to investigate the probabilistic effects of acidified seawater on the life-stage response dynamics of fertilization, larvae growth, and larvae mortality of the green sea urchin (Strongylocentrotus droebachiensis). We incorporated the regulation of primary body cavity (PBC) pH in response to seawater pH into the assessment by constructing an explicit model to assess effective life-stage response dynamics to seawater or PBC pH levels. The likelihood of exposure to ocean acidification was also evaluated by addressing the uncertainties of the risk characterization. For unsuccessful fertilization, the estimated 50% effect level of seawater acidification (EC50 SW ) was 0.55 ± 0.014 (mean ± SE) pH units. This life stage was more sensitive than growth inhibition and mortality, for which the EC50 values were 1.13 and 1.03 pH units, respectively. The estimated 50% effect levels of PBC pH (EC50 PBC ) were 0.99 ± 0.05 and 0.88 ± 0.006 pH units for growth inhibition and mortality, respectively. We also predicted the probability distributions for seawater and PBC pH levels in 2100. The level of unsuccessful fertilization had 50 and 90% probability risks of 5.07-24.51 (95% CI) and 0-6.95%, respectively. We conclude that this probabilistic risk analysis model is parsimonious enough to quantify the multiple vulnerabilities of the green sea urchin while addressing the systemic effects of ocean acidification. This study found a high potential risk of acidification affecting the fertilization of the green sea urchin, whereas there was no evidence for adverse effects on growth and mortality resulting from exposure to the predicted acidified environment.

Tolerance of cultivated and wild plants of different taxonomy to soil contamination by kerosene.

PubMed

Sharonova, Natalia; Breus, Irina

2012-05-01

In laboratory experiments on leached chernozem contaminated by kerosene (1-15 wt.%), germination of 50 plants from 21 families (cultivated and wild, annual and perennial, mono- and dicotyledonous) as affected by kerosene type and concentration and plant features was determined. Tested plants formed three groups: more tolerant, less tolerant, and intolerant, in which relative germination was more than 70%, 30-70% and less than 30%, respectively. As parameters of soil phytotoxicity, effective kerosene concentrations (EC) causing germination depression of 10%, 25% and 50% were determined. EC values depended on the plant species and varied in a wide range of kerosene concentrations: 0.02-7.3% (EC(10)), 0.05-8.1% (EC(25)), and 0.2-12.7% (EC(50)). The reported data on germination in soils contaminated by oil and petrochemicals were generalized. The comparison showed that at very high contamination levels (10 and 15%) kerosene was 1.3-1.6 times more phytotoxic than diesel fuel and 1.3-1.4 times more toxic than crude oil, and at low (1 and 2%) and medium (3 and 5%) levels the toxicity of these contaminants was close differing by a factor of 1.1-1.2. Tolerance of plants to soil contamination had a species-specific nature and, on the average, decreased in the following range of families: Fabaceae (germination decrease of 10-60% as compared to an uncontaminated control)>Brassicaceae (5-70%)>Asteraceae (25-95%)>Poaceae (10-100%). The monocotyledonous species tested were characterized as medium- and low-stable to contamination, whereas representatives of dicotyledonous plants were met in all groups of tolerance. Tested wild plants, contrary to reference data on oil toxicity, were more sensitive to kerosene than cultivated. No correlation was observed between degree of plant tolerance to kerosene and mass of seeds. The evidence indicates factors as structure and properties of testa, structure of germ, type of storage compounds, and type of seed germination (underground or aboveground) are more important. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of Nickel, Chlorpyrifos and Their Mixture on the Dictyostelium discoideum Proteome

PubMed Central

Boatti, Lara; Robotti, Elisa; Marengo, Emilio; Viarengo, Aldo; Marsano, Francesco

2012-01-01

Mixtures of chemicals can have additive, synergistic or antagonistic interactions. We investigated the effects of the exposure to nickel, the organophosphate insecticide chlorpyrifos at effect concentrations (EC) of 25% and 50% and their binary mixture (Ec25 + EC25) on Dictyostelium discoideum amoebae based on lysosomal membrane stability (LMS). We treated D. discoideum with these compounds under controlled laboratory conditions and evaluated the changes in protein levels using a two-dimensional gel electrophoresis (2DE) proteomic approach. Nickel treatment at EC25 induced changes in 14 protein spots, 12 of which were down-regulated. Treatment with nickel at EC50 resulted in changes in 15 spots, 10 of which were down-regulated. Treatment with chlorpyrifos at EC25 induced changes in six spots, all of which were down-regulated; treatment with chlorpyrifos at EC50 induced changes in 13 spots, five of which were down-regulated. The mixture corresponding to EC25 of each compound induced changes in 19 spots, 13 of which were down-regulated. The data together reveal that a different protein expression signature exists for each treatment, and that only a few proteins are modulated in multiple different treatments. For a simple binary mixture, the proteomic response does not allow for the identification of each toxicant. The protein spots that showed significant differences were identified by mass spectrometry, which revealed modulations of proteins involved in metal detoxification, stress adaptation, the oxidative stress response and other cellular processes. PMID:23443088

Signals of Opportunity Navigation Using Wi-Fi Signals

DTIC Science & Technology

2011-03-24

Identifier . . . . . . . . . . . . . . . . . . . . . . . 54 MVM Mean Value Method . . . . . . . . . . . . . . . . . . . . . 60 SDM Scaled Differential...the mean value ( MVM ) and scaled differential (SDM) methods. An error was logged if the UI 60 correlation algorithm identified a packet index that did...Notable from this graph is that a window of 50 packets appears to provide zero errors for MVM and near zero errors for SDM. Also notable is that a

Vasorelaxant properties of Vernonia amygdalina ethanol extract and its possible mechanism.

PubMed

Ch'ng, Yung Sing; Loh, Yean Chun; Tan, Chu Shan; Ahmad, Mariam; Asmawi, Mohd Zaini; Wan Omar, Wan Maznah; Yam, Mun Fei

2017-12-01

Vernonia amygdalina Del. (VA) (Asteraceae) is commonly used to treat hypertension in Malaysia. This study investigates the vasorelaxant mechanism of VA ethanol extract (VAE) and analyzes its tri-step FTIR spectroscopy fingerprint. Dried VA leaves were extracted with ethanol through maceration and concentrated using rotary evaporator before freeze-dried. The vasorelaxant activity and the underlying mechanisms of VAE using the cumulative concentration (0.01-2.55 mg/mL at 20-min intervals) were evaluated on aortic rings isolated from Sprague Dawley rats in the presence of antagonists. The tri-step FTIR spectroscopy showed that VAE contains alkaloids, flavonoids, and saponins. VAE caused the relaxation of pre-contracted aortic rings in the presence and absence of endothelium with EC 50 of 0.057 ± 0.006 and 0.430 ± 0.196 mg/mL, respectively. In the presence of Nω-nitro-l-arginine methyl ester (EC 50 0.971 ± 0.459 mg/mL), methylene blue (EC 50 1.203 ± 0.426 mg/mL), indomethacin (EC 50 2.128 ± 1.218 mg/mL), atropine (EC 50 0.470 ± 0.325 mg/mL), and propranolol (EC 50 0.314 ± 0.032 mg/mL), relaxation stimulated by VAE was significantly reduced. VAE acted on potassium channels, with its vasorelaxation effects significantly reduced by tetraethylammonium, 4-aminopyridine, barium chloride, and glibenclamide (EC 50 0.548 ± 0.184, 0.158 ± 0.012, 0.847 ± 0.342, and 0.304 ± 0.075 mg/mL, respectively). VAE was also found to be active in reducing Ca 2+ released from the sarcoplasmic reticulum and blocking calcium channels. The vasorelaxation effect of VAE involves upregulation of NO/cGMP and PGI 2 signalling pathways, and modulation of calcium/potassium channels, and muscarinic and β 2 -adrenergic receptor levels.

EC-QCL mid-IR transmission spectroscopy for monitoring dynamic changes of protein secondary structure in aqueous solution on the example of β-aggregation in alcohol-denaturated α-chymotrypsin.

PubMed

Alcaráz, Mirta R; Schwaighofer, Andreas; Goicoechea, Héctor; Lendl, Bernhard

2016-06-01

In this work, a novel EC-QCL-based setup for mid-IR transmission measurements in the amide I region is introduced for monitoring dynamic changes in secondary structure of proteins. For this purpose, α-chymotrypsin (aCT) acts as a model protein, which gradually forms intermolecular β-sheet aggregates after adopting a non-native α-helical structure induced by exposure to 50 % TFE. In order to showcase the versatility of the presented setup, the effects of varying pH values and protein concentration on the rate of β-aggregation were studied. The influence of the pH value on the initial reaction rate was studied in the range of pH 5.8-8.2. Results indicate an increased aggregation rate at elevated pH values. Furthermore, the widely accessible concentration range of the laser-based IR transmission setup was utilized to investigate β-aggregation across a concentration range of 5-60 mg mL(-1). For concentrations lower than 20 mg mL(-1), the aggregation rate appears to be independent of concentration. At higher values, the reaction rate increases linearly with protein concentration. Extended MCR-ALS was employed to obtain pure spectral and concentration profiles of the temporal transition between α-helices and intermolecular β-sheets. Comparison of the global solutions obtained by the modelled data with results acquired by the laser-based IR transmission setup at different conditions shows excellent agreement. This demonstrates the potential and versatility of the EC-QCL-based IR transmission setup to monitor dynamic changes of protein secondary structure in aqueous solution at varying conditions and across a wide concentration range. Graphical abstract EC-QCL IR spectroscopy for monitoring protein conformation change.

Application of a fluorometric microplate algal toxicity assay for riverine periphytic algal species.

PubMed

Nagai, Takashi; Taya, Kiyoshi; Annoh, Hirochica; Ishihara, Satoru

2013-08-01

Although riverine periphytic algae attached to riverbed gravel are dominant species in flowing rivers, there is limited toxicity data on them because of the difficulty in cell culture and assays. Moreover, it is well known that sensitivity to pesticides differ markedly among species, and therefore the toxicity data for multiple species need to be efficiently obtained. In this study, we investigated the use of fluorometric microplate toxicity assay for testing periphytic algal species. We selected five candidate test algal species Desmodesmus subspicatus, Achnanthidium minutissimum, Navicula pelliculosa, Nitzschia palea, and Pseudanabaena galeata. The selected species are dominant in the river, include a wide range of taxon, and represent actual species composition. Other additional species were also used to compare the sensitivity and suitability of the microplate assay. A 96-well microplate was used as a test chamber and algal growth was measured by in-vivo fluorescence. Assay conditions using microplate and fluorometric measurement were established, and sensitivities of 3,5-dichlorophenol as a reference substance were assayed. The 50 percent effect concentrations (EC50s) obtained by fluorometric microplate assay and those obtained by conventional Erlenmeyer flask assay conducted in this study were consistent. Moreover, the EC50 values of 3,5-dichlorophenol were within the reported confidence intervals in literature. These results supported the validity of our microplate assay. Species sensitivity distribution (SSD) analysis was conducted using the EC50s of five species. The SSD was found to be similar to the SSD obtained using additional tested species, suggesting that SSD using the five species largely represents algal sensitivity. Our results provide a useful and efficient method for high-tier probabilistic ecological risk assessment of pesticides. Copyright © 2013 Elsevier Inc. All rights reserved.

Synthesis and Biological Evaluation of 3-Benzylidene-4-chromanone Derivatives as Free Radical Scavengers and α-Glucosidase Inhibitors.

PubMed

Takao, Koichi; Yamashita, Marimo; Yashiro, Aruki; Sugita, Yoshiaki

2016-01-01

A series of 3-benzylidene-4-chromanone derivatives (3-20) were synthesized and the structure-activity relationships for antioxidant and α-glucosidase inhibitory activities were evaluated. Among synthesized compounds, compounds 5, 13, 18, which contain catechol moiety, showed the potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity (5: EC50 13 µM; 13: EC50 14 µM; 18: EC50 13 µM). The compounds 12, 14, 18 showed higher α-glucosidase inhibitory activity (12: IC50 15 µM; 14: IC50 25 µM; 18: IC50 28 µM). The compound 18 showed both of potent DPPH radical scavenging and α-glucosidase inhibitory activities. These data suggest that 3-benzylidene-4-chromanone derivatives, such as compound 18, may serve as the lead compound for the development of novel α-glucosidase inhibitors with antioxidant activity.

Extracolonic Cancer in Inflammatory Bowel Disease: Data from the GETECCU Eneida Registry.

PubMed

Chaparro, María; Ramas, M; Benítez, J M; López-García, A; Juan, A; Guardiola, J; Mínguez, M; Calvet, X; Márquez, L; Fernández Salazar, L I; Bujanda, L; García, C; Zabana, Y; Lorente, R; Barrio, J; Hinojosa, E; Iborra, M; Cajal, M Domínguez; Van Domselaar, M; García-Sepulcre, M F; Gomollón, F; Piqueras, M; Alcaín, G; García-Sánchez, V; Panés, J; Domènech, E; García-Esquinas, E; Rodríguez-Artalejo, F; Gisbert, J P

2017-07-01

The objective of this study was (a) To know the prevalence and distribution of extracolonic cancer (EC) in patients with inflammatory bowel disease (IBD); (b) To estimate the incidence rate of EC; (c) To evaluate the association between EC and treatment with immunosuppressants and anti-tumor necrosis factor (TNF) agents. This was an observational cohort study. IBD and inclusion in the ENEIDA Project (a prospectively maintained registry) from GETECCU. Patients with EC before the diagnosis of IBD, lack of relevant data for this study, and previous treatment with immunosuppressants other than corticosteroids, thiopurines, methotrexate, or anti-TNF agents. The Kaplan-Meier method was used to evaluate the impact of several variables on the risk of EC, and any differences between survival curves were evaluated using the log-rank test. Stepwise multivariate Cox regression analysis was used to investigate factors potentially associated with the development of EC, including drugs for the treatment of IBD, during follow-up. A total of 11,011 patients met the inclusion criteria and were followed for a median of 98 months. Forty-eight percent of patients (5,303) had been exposed to immunosuppressants or anti-TNF drugs, 45.8% had been exposed to thiopurines, 4.7% to methotrexate, and 21.6% to anti-TNF drugs. The prevalence of EC was 3.6%. In the multivariate analysis, age (HR=1.05, 95% CI=1.04-1.06) and having smoked (hazards ratio (HR)=1.47, 95% confidence interval (CI)=1.10-1.80) were the only variables associated with a higher risk of EC. Neither immunosuppressants nor anti-TNF drugs seem to increase the risk of EC. Older age and smoking were associated with a higher prevalence of EC.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Kee Sung; Rajput, Nav Nidhi; Persson, Kristin A.

Ferrocene (Fc) and N-(ferrocenylmethyl)-N,N-dimethyl-N-ethylammonium bistrifluoromethyl-sulfonimide (Fc1N112-TFSI) were dissolved in carbonate solvents and self-diffusion coefficients (D) of solutes and solvents were measured by {sup 1}H and {sup 19}F pulsed field gradient nuclear magnetic resonance (NMR) spectroscopy. The organic solvents were propylene carbonate (PC), ethyl methyl carbonate (EMC), and a ternary mixture that also includes ethylene carbonate (EC). Results from NMR studies over the temperature range of 0–50 °C and for various concentrations (0.25–1.7 M) of Fc1N112-TFSI are compared to values of D simulated with classical molecular dynamics (MD). The measured self-diffusion coefficients gradually decreased as the Fc1N112-TFSI concentration increased in allmore » solvents. Since TFSI{sup −} has fluoromethyl groups (CF{sub 3}), D{sub TFSI} could be measured separately and the values found are larger than those for D{sub Fc1N112} in all samples measured. The EC, PC, and EMC have the same D in the neat solvent mixture and when Fc is dissolved in EC/PC/EMC at a concentration of 0.2 M, probably due to the interactions between common carbonyl structures within EC, PC, and EMC. A difference in D (D{sub PC} < D{sub EC} < D{sub EMC}), and both a higher E{sub a} for translational motion and higher effective viscosity for PC in the mixture containing Fc1N112-TFSI reflect the interaction between PC and Fc1N112{sup +}, which is a relatively stronger interaction than that between Fc1N112{sup +} and other solvent species. In the EC/PC/EMC solution that is saturated with Fc1N112-TFSI, we find that D{sub PC} = D{sub EC} = D{sub EMC} and Fc1N112{sup +} and all components of the EC/PC/EMC solution have the same E{sub a} for translational motion, while the ratio D{sub EC/PC/EMC}/D{sub Fc1N112} is approximately 3. These results reflect the lack of available free volume for independent diffusion in the saturated solution. The Fc1N112{sup +} transference numbers lie around 0.4 and increase slightly as the temperature is increased in the PC and EMC solvents. The trends observed for D from simulations are in good agreement with experimental results and provide molecular level understanding of the solvation structure of Fc1N112-TFSI dissolved in EC/PC/EMC.« less

Pharmacological characterization of the 5-HT receptor-mediated contraction in the mouse isolated ileum

PubMed Central

Tuladhar, B R; Womack, M D; Naylor, R J

2000-01-01

The pharmacological characterization of a 5-HT receptor-mediated contractile response in the mouse isolated ileum is described. In the presence of methysergide (1 μM), 5-hydroxytryptamine (5-HT, 0.3–100 μM) produced phasic concentration-dependent contractions of segments of the mouse isolated ileum with a pEC50 value of 5.47±0.09. The 5-HT3 receptor selective agonists m-chlorophenylbiguanide (0.3–100 μM, pEC50 5.81±0.04), 1-phenylbiguanide (3–100 μM, pEC50 5.05±0.06) and 2-methyl-5-HT (3–100 μM, pEC50 5.00±0.07) acted as full agonists to induce contractile responses. 5-methoxytryptamine (0.1–100 μM), RS 67506 (0.1–100 μM) and α-methyl-5-HT (0.1–100 μM) failed to mimic the 5-HT responses. The contractile response to 5-HT was not antagonized by either 5-HT2 receptor antagonists ritanserin (0.1 μM) or ketanserin (1 μM) nor the 5-HT4 receptor antagonist SB 204070 (0.1 μM). The 5-HT3 receptor selective antagonists granisetron (0.3–1 nM), tropisetron (1–10 nM), ondansetron (10 nM–1 μM) and MDL 72222 (10 nM–1 μM) caused rightward displacement of the concentration-response curves to 5-HT. The lower concentrations of the antagonists caused approximate parallel rightward shifts of the concentration-response curves to 5-HT with apparent pKB values for granisetron (9.70±0.39), tropisetron (9.18±0.20), ondansetron (8.84±0.24) and MDL 72222 (8.65±0.35). But higher concentrations of antagonists resulted in a progressive reduction in the maximum responses. The contractile response to 5-HT was abolished by tetrodotoxin (0.3 μM); atropine (0.1 and 1 μM) decreased the maximum response of the 5-HT concentration-response curve by approximately 65%. It is concluded that a neuronally located 5-HT3 receptor mediates a contractile response to 5-HT in the mouse ileum. The 5-HT3 receptor in the mouse ileum has a different pharmacological profile to that reported for the guinea-pig ileum. PMID:11139451

Anti-herpes virus activities of bioactive fraction and isolated pure constituent of Mallotus peltatus: an ethnomedicine from Andaman Islands

PubMed Central

2012-01-01

Background Viral infections, particularly the infections caused by herpes simplex virus (HSV), represent one of the most serious public health concerns globally because of their devastating impact. The aim of this study was to evaluate the antiviral potential of methanolic crude extract of an ethnomedicine Mallotus peltatus, its active fraction and pure compound, against HSV-1 F and HSV-2 G. Result The cytotoxicity (CC50, the concentration of 50% cellular toxicity), antiviral effective concentration (EC50, the concentration required to achieve 50% protection against virus-induced cytopathic effect), plaque reduction and the selectivity index (SI, the ratio of CC50 and EC50) was determined. Results showed that the crude methanolic extract of M. peltatus possessed weak anti-HSV activity. In contrast, the active fraction A and isolated ursolic acid from fraction A exhibited potent antiherpesvirus activity against both HSV-1 (EC50 = 7.8 and 5.5 μg/ml; SI = 22.3 and 20) and HSV-2 (EC50 = 8.2 and 5.8 μg/ml, and SI = 21.2 and 18.97). The fraction A and isolated ursolic acid (10 μg/ml) inhibited plaque formation of HSV-1 and HSV-2 at more than 80% levels, with a dose dependent antiviral activity, compared to acyclovir. The time response study revealed that the anti-HSV activity of fraction A and isolated ursolic acid is highest at 2–5 h post-infection. Moreover, the time kinetics study by indirect immunofluorescence assay showed a characteristic pattern of small foci of single fluorescent cells in fraction A- treated virus infected cells at 2 h and 4 h post-infection, suggesting drug inhibited viral dissemination. Further, the PCR study with infected cell cultures treated with fraction A and isolated ursolic acid at various time intervals, failed to show amplification at 48–72 h, like acyclovir treated HSV-infected cells. Moreover, fraction A or isolated ursolic acid showed no interaction in combination with acyclovir. Conclusion This study revealed that bioactive fraction A and isolated ursolic acid of M. peltatus has good anti-HSV activity, probably by inhibiting the early stage of multiplication (post-infection of 0–5 h), with SI value of 20, suggesting its potential use as anti-HSV agents. PMID:22624581

Global validation of a process-based model on vegetation gross primary production using eddy covariance observations.

PubMed

Liu, Dan; Cai, Wenwen; Xia, Jiangzhou; Dong, Wenjie; Zhou, Guangsheng; Chen, Yang; Zhang, Haicheng; Yuan, Wenping

2014-01-01

Gross Primary Production (GPP) is the largest flux in the global carbon cycle. However, large uncertainties in current global estimations persist. In this study, we examined the performance of a process-based model (Integrated BIosphere Simulator, IBIS) at 62 eddy covariance sites around the world. Our results indicated that the IBIS model explained 60% of the observed variation in daily GPP at all validation sites. Comparison with a satellite-based vegetation model (Eddy Covariance-Light Use Efficiency, EC-LUE) revealed that the IBIS simulations yielded comparable GPP results as the EC-LUE model. Global mean GPP estimated by the IBIS model was 107.50±1.37 Pg C year(-1) (mean value ± standard deviation) across the vegetated area for the period 2000-2006, consistent with the results of the EC-LUE model (109.39±1.48 Pg C year(-1)). To evaluate the uncertainty introduced by the parameter Vcmax, which represents the maximum photosynthetic capacity, we inversed Vcmax using Markov Chain-Monte Carlo (MCMC) procedures. Using the inversed Vcmax values, the simulated global GPP increased by 16.5 Pg C year(-1), indicating that IBIS model is sensitive to Vcmax, and large uncertainty exists in model parameterization.

Alpha-glucosidase Inhibitory and Antioxidant Potential of Antidiabetic Herb Alternanthera sessilis: Comparative Analyses of Leaf and Callus Solvent Fractions.

PubMed

Chai, Tsun-Thai; Khoo, Chee-Siong; Tee, Chong-Siang; Wong, Fai-Chu

2016-01-01

Alternanthera sessilis is a medicinal herb which is consumed as vegetable and used as traditional remedies of various ailments in Asia and Africa. This study aimed to investigate the antiglucosidase and antioxidant activity of solvent fractions of A. sessilis leaf and callus. Leaf and callus methanol extracts were fractionated to produce hexane, chloroform, ethyl acetate, butanol, and water fractions. Antiglucosidase and 1,1-diphenyl-2-picrylhydrazyl scavenging activities as well as total phenolic (TP), total flavonoid (TF), and total coumarin (TC) contents were evaluated. Lineweaver-Burk plot analysis was performed on leaf and callus fractions with the strongest antiglucosidase activity. Leaf ethyl acetate fraction (LEF) had the strongest antiglucosidase (EC 50 0.55 mg/mL) and radical scavenging (EC 50 10.81 μg/mL) activity among leaf fractions. Callus ethyl acetate fraction (CEF) and chloroform fraction had the highest antiglucosidase (EC 50 0.25 mg/mL) and radical scavenging (EC 50 34.12 μg/mL) activity, respectively, among callus fractions. LEF and CEF were identified as noncompetitive and competitive α-glucosidase inhibitors, respectively. LEF and CEF had greater antiglucosidase activity than acarbose. Leaf fractions had higher phytochemical contents than callus fractions. LEF had the highest TP, TF, and TC contents. Antiglucosidase and antioxidant activities of leaf fractions correlated with phytochemical contents. LEF had potent antiglucosidase activity and concurrent antioxidant activity. CEF had the highest antiglucosidase activity among all fractions. Callus culture is a promising tool for enhancing production of potent α-glucosidase inhibitors. Leaf ethyl acetate fraction (LEF) had the strongest antiglucosidase (EC 50 0.55 mg/mL) and radical scavenging (EC 50 10.81 μg/mL) activity among leaf fractionsCallus ethyl acetate fraction (CEF) and chloroform fraction had the highest antiglucosidase (EC 50 0.25 mg/mL) and radical scavenging (EC 50 34.12 μg/mL) activity, respectively, among callus fractionsLEF and CEF were identified as noncompetitive and competitive á-glucosidase inhibitors, respectivelyAntiglucosidase and antioxidant activities of leaf fractions correlated with phytochemical contents. Abbreviations used: LHF: Leaf hexane fraction, LCF: Leaf chloroform fraction, LEF: Leaf ethyl acetate fraction, LBF: Leaf butanol fraction, LWF: Leaf water fraction, CHF: Callus hexane fraction, CCF: Callus chloroform fraction, CEF: Callus ethyl acetate fraction, CBF: Callus butanol fraction, CWF: Callus water fraction, TP: Total phenolic, TF: Total flavonoid, TC: Total coumarin.

Safety and pharmacokinetics of dapivirine delivery from matrix and reservoir intravaginal rings to HIV-negative women.

PubMed

Nel, Annalene; Smythe, Shanique; Young, Katherine; Malcolm, Karl; McCoy, Clare; Rosenberg, Zeda; Romano, Joseph

2009-08-01

Vaginal microbicides for the prevention of HIV transmission may be an important option for protecting women from infection. Incorporation of dapivirine, a lead candidate nonnucleoside reverse transcriptase inhibitor, into intravaginal rings (IVRs) for sustained mucosal delivery may increase microbicide product adherence and efficacy compared with conventional vaginal formulations. Twenty-four healthy HIV-negative women 18-35 years of age were randomly assigned (1:1:1) to dapivirine matrix IVR, dapivirine reservoir IVR, or placebo IVR. Dapivirine concentrations were measured in plasma and vaginal fluid samples collected at sequential time points over the 33-day study period (28 days of IVR use, 5 days of follow-up). Safety was assessed by pelvic/colposcopic examinations, clinical laboratory tests, and adverse events. Both IVR types were safe and well tolerated with similar adverse events observed in the placebo and dapivirine groups. Dapivirine from both IVR types was successfully distributed throughout the lower genital tract at concentrations over 4 logs greater than the EC50 against wild-type HIV-1 (LAI) in MT4 cells. Maximum concentration (Cmax) and area under the concentration-time curve (AUC) values were significantly higher with the matrix than reservoir IVR. Mean plasma concentrations of dapivirine were <2 ng/mL. These findings suggest that IVR delivery of microbicides is a viable option meriting further study.

Bioavailability of Antibiotics at Soil-Water Interfaces: A Comparison of Measured Activities and Equilibrium Partitioning Estimates.

PubMed

Menz, Jakob; Müller, Julia; Olsson, Oliver; Kümmerer, Klaus

2018-06-05

There are growing concerns that antibiotic pollution impacts environmental microbiota and facilitates the propagation of antibiotic resistance. However, the prediction or analytical determination of bioavailable concentrations of antibiotics in soil is still subject to great uncertainty. Biological assays are increasingly recognized as valuable complementary tools that allow a more direct determination of the residual antibiotic activity. This study assessed the bioavailability of structurally diverse antibiotics at a soil-water interface applying activity-based analyses in conjunction with equilibrium partitioning (EqP) modeling. The activity against Gram-positive and Gram-negative bacteria of nine antibiotics from different classes was determined in the presence and absence of standard soil (LUFA St. 2.2). The addition of soil affected the activity of different antibiotics to highly varying degrees. Moreover, a highly significant correlation ( p < 0.0001) between the experimentally observed and the EqP-derived log EC 50 (half-maximal effective concentration) values was observed. The innovative experimental design of this study provided new insights on the bioavailability of antibiotics at soil-water interfaces. EqP appears to be applicable to a broad range of antibiotics for the purpose of screening-level risk assessment. However, EqP estimates cannot replace soil-specific ecotoxicity testing in higher-tier assessments, since their accuracy is still compromised by a number of factors.

Toxicological properties of thio- and alkylphenols causing flavor tainting in fish from the upper Wisconsin River

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heil, T.P.; Lindsay, R.C.

1989-08-01

EC50 Microtox (5 min, 25 degrees C) assay values for 2-isopropylphenol, 3-isopropylphenol, 4-isopropylphenol, 2,4-diisopropylphenol, 2,5-diisopropylphenol 2,6-diisopropylphenol, 3,5-diisopropylphenol, carvacrol, thymol, thiophenol, and thiocresol ranged from 2 x 10(-2) mM for thymol (least toxic) to 2 x 10(-4) mM for 2,4-diisopropylphenol and 4-isopropylphenol (most toxic).

Novel triterpenoids isolated from raisins exert potent antiproliferative activities by targeting mitochondrial and Ras/Raf/ERK signaling in human breast cancer cells.

PubMed

Liu, Juan; Wang, Yihai; Liu, Rui Hai; He, Xiangjiu

2016-07-13

Raisins are produced in many regions of the world and may be eaten raw or used in cooking, baking and brewing. Bioactivity-guided fractionation of raisins was used to determine the chemical identity of bioactive constituents. Seven triterpenoids, including three novel triterpenoids, were isolated and identified. The novel triterpenoids were elucidated to be 3β,13β-dihydroxy-12,13-dihydrooleanolic acid (1), 3β,12β,13β-trihydroxy-12,13-dihydrooleanolic acid (2, TOA), and 3β,13β-dihydroxy-12,13-dihydroursolic acid (7), respectively. TOA showed the highest antiproliferative activity against MCF-7/DOX cells, with an EC50 value of 3.60 ± 0.55 μM. Compounds 1, 3 and 7 also exhibited potent antiproliferative activity against MCF-7/DOX cells, with an EC50 value of 7.10 ± 0.65, 10.22 ± 0.90 and 8.91 ± 1.12 μM. Compounds 1 and 2 also exhibited potent antioxidant activities. Moreover, the detailed cytotoxic mechanisms of TOA were investigated by targeting the mitochondrial and protein tyrosine kinase signaling (Ras/Raf/ERK). The results strongly demonstrated that the novel triterpenoids isolated from raisins could be promising candidates for therapy of breast cancer.

Development of acute and chronic sediment bioassays with the harpacticoid copepod Quinquelaophonte sp.

PubMed

Stringer, Tristan J; Glover, Chris N; Keesing, Vaughan; Northcott, Grant L; Gaw, Sally; Tremblay, Louis A

2014-01-01

Reliable environmentally realistic bioassay methodologies are increasingly needed to assess the effects of environmental pollution. This study describes two estuarine sediment bioassays, one acute (96 h) and one chronic (14 d), with the New Zealand harpacticoid copepod Quinquelaophonte sp. utilising behavioural and reproductive endpoints. Spiked sediments were used to expose Quinquelaophonte sp. to three reference compounds representing important categories of estuarine chemical stressors: zinc (a metal), atrazine (a pesticide), and phenanthrene (a polycyclic aromatic hydrocarbon). Acute-to-chronic ratios (ACR) were used to further characterise species responses. Acute sediment (sandy and low total organic content) 96 h EC50 values for the sublethal inhibition of mobility for zinc, atrazine and phenanthrene were 137, 5.4, and 2.6 µg/g, respectively. The chronic EC50 values for inhibition of reproduction (total offspring) were 54.5, 0.0083, and 0.067 µg/g for zinc, atrazine, and phenanthrene, respectively. For phenanthrene, a potentially novel mode of action was identified on reproduction. Quinquelaophonte sp. was found to be more sensitive than several other estuarine species indicating choice of test organism is important to characterising the effects of environmentally relevant levels of contamination. The bioassay sediment results demonstrate the sensitivity and suitability of Quinquelaophonte sp. as a tool for the assessment use of estuarine health. © 2013 Published by Elsevier Inc.

(Eco)toxicity and biodegradability of selected protic and aprotic ionic liquids.

PubMed

Peric, Brezana; Sierra, Jordi; Martí, Esther; Cruañas, Robert; Garau, Maria Antonia; Arning, Jürgen; Bottin-Weber, Ulrike; Stolte, Stefan

2013-10-15

Ionic liquids (ILs) are a promising group of compounds with a large variety of possible structures and uses. They are considered as a potential "green" replacement for traditional volatile organic solvents, but their impact on the environment is often neglected or not studied enough. In the present study, selected representatives of two ILs groups were analyzed: a new family of protic ILs (derived from aliphatic amines and organic acids) and some frequently used aprotic ILs (substituted imidazolium and piridinium chlorides). The aquatic toxicity (test organisms Vibrio fischeri, Pseudokirchneriella subcapitata and Lemna minor) and biodegradability tests were carried out. The additional tests with enzyme (acetylcholinesterase) and leukemia rat cells (IPC-81) provided more in-depth evaluation of toxicity. In our comparative hazard assessment protic ILs have EC50 values >100 mg L(-1) in all of the tests performed, except in the case of three representatives toward Lemna minor. They also show good biodegradability rates. The EC50 values for aprotic ILs are various orders of magnitude lower than the ones for protic ILs in most of the tests and they show a lower biodegradability potential. These findings indicate that protic ILs can be considered as environmentally safer alternatives for more toxic ILs and organic solvents. Copyright © 2013 Elsevier B.V. All rights reserved.

Comparison of experimental methods for determination of toxicity and biodegradability of xenobiotic compounds.

PubMed

Polo, A M; Tobajas, M; Sanchis, S; Mohedano, A F; Rodríguez, J J

2011-07-01

Different methods for determining the toxicity and biodegradability of hazardous compounds evaluating their susceptibility to biological treatment were studied. Several compounds including chlorophenols and herbicides have been evaluated. Toxicity was analyzed in terms of EC50 and by a simple respirometric procedure based on the OECD Method 209 and by the Microtox® bioassay. The values of EC50 obtained from respirometry were in all the cases higher than those from the Microtox® test. The respirometric inhibition values of chlorophenols were related well with the number of chlorine atoms and their position in the aromatic ring. In general, herbicides showed lower inhibition, being alachlor the less toxic from this criterion. For determination of biodegradability an easier and faster alternative to the OECD Method 301, with a higher biomass to substrate ratio is proposed. When this test was negative, the Zahn-Wellens one was performed in order to evaluate the inherent biodegradability. In the fast test of biodegradability, 4-chlorocatechol and 4-chlorophenol showed a complete biodegradation by an unacclimated sludge upon 48 h. These results together with their low respirometric inhibition, allow concluding that these compounds could be conveniently removed in a WWTP. Alachlor, 2,4-dichlorophenol, 2,4,6-trichlorophenol and MCPA showed a partial biodegradation upon 28 days by the Zahn-Wellens inherent biodegradability test.

Phytotoxicity of 15 common pharmaceuticals on the germination of Lactuca sativa and photosynthesis of Chlamydomonas reinhardtii.

PubMed

Pino, Ma Rosa; Muñiz, Selene; Val, Jonatan; Navarro, Enrique

2016-11-01

Pharmaceuticals reach terrestrial environments through the application of treated wastewaters and biosolids to agricultural soils. We have investigated the toxicity of 15 common pharmaceuticals, classified as nonsteroidal anti-inflammatory drugs (NSAIDs), blood lipid-lowering agents, β-blockers and antibiotics, in two photosynthetic organisms. Twelve pharmaceuticals caused inhibitory effects on the radicle and hypocotyl elongation of Lactuca sativa seeds. The EC 50 values obtained were in the range of 170-5656 mg L -1 in the case of the radicle and 188-4558 mg L -1 for the hypocotyl. Propranolol was the most toxic drug for both root and hypocotyl elongation, followed by the NSAIDs, then gemfibrozil and tetracycline. Other effects, such as root necrosis, inhibition of root growth and curly hairs, were detected. However, even at the highest concentrations tested (3000 mg L -1 ), seed germination was not affected. NSAIDs decreased the photosynthetic yield of Chlamydomonas reinhardtii, but only salicylic acid showed EC 50 values below 1000 mg L -1 . The first effects detected at low concentrations, together with the concentrations found in environmental samples, indicate that the use of biosolids and wastewaters containing pharmaceuticals should be regulated and their compositions assessed in order to prevent medium- and long-term impacts on agricultural soils and crops.

High Precision Determination of the β Decay Q(EC) Value of (11)C and Implications on the Tests of the Standard Model.

PubMed

Gulyuz, K; Bollen, G; Brodeur, M; Bryce, R A; Cooper, K; Eibach, M; Izzo, C; Kwan, E; Manukyan, K; Morrissey, D J; Naviliat-Cuncic, O; Redshaw, M; Ringle, R; Sandler, R; Schwarz, S; Sumithrarachchi, C S; Valverde, A A; Villari, A C C

2016-01-08

We report the determination of the Q(EC) value of the mirror transition of (11)C by measuring the atomic masses of (11)C and (11)B using Penning trap mass spectrometry. More than an order of magnitude improvement in precision is achieved as compared to the 2012 Atomic Mass Evaluation (Ame2012) [Chin. Phys. C 36, 1603 (2012)]. This leads to a factor of 3 improvement in the calculated Ft value. Using the new value, Q(EC)=1981.690(61)  keV, the uncertainty on Ft is no longer dominated by the uncertainty on the Q(EC) value. Based on this measurement, we provide an updated estimate of the Gamow-Teller to Fermi mixing ratio and standard model values of the correlation coefficients.

An Image Analysis Algorithm for Malaria Parasite Stage Classification and Viability Quantification

PubMed Central

Moon, Seunghyun; Lee, Sukjun; Kim, Heechang; Freitas-Junior, Lucio H.; Kang, Myungjoo; Ayong, Lawrence; Hansen, Michael A. E.

2013-01-01

With more than 40% of the world’s population at risk, 200–300 million infections each year, and an estimated 1.2 million deaths annually, malaria remains one of the most important public health problems of mankind today. With the propensity of malaria parasites to rapidly develop resistance to newly developed therapies, and the recent failures of artemisinin-based drugs in Southeast Asia, there is an urgent need for new antimalarial compounds with novel mechanisms of action to be developed against multidrug resistant malaria. We present here a novel image analysis algorithm for the quantitative detection and classification of Plasmodium lifecycle stages in culture as well as discriminating between viable and dead parasites in drug-treated samples. This new algorithm reliably estimates the number of red blood cells (isolated or clustered) per fluorescence image field, and accurately identifies parasitized erythrocytes on the basis of high intensity DAPI-stained parasite nuclei spots and Mitotracker-stained mitochondrial in viable parasites. We validated the performance of the algorithm by manual counting of the infected and non-infected red blood cells in multiple image fields, and the quantitative analyses of the different parasite stages (early rings, rings, trophozoites, schizonts) at various time-point post-merozoite invasion, in tightly synchronized cultures. Additionally, the developed algorithm provided parasitological effective concentration 50 (EC50) values for both chloroquine and artemisinin, that were similar to known growth inhibitory EC50 values for these compounds as determined using conventional SYBR Green I and lactate dehydrogenase-based assays. PMID:23626733

Production of monodisperse epigallocatechin gallate (EGCG) microparticles by spray drying for high antioxidant activity retention.

PubMed

Fu, Nan; Zhou, Zihao; Jones, Tyson Byrne; Tan, Timothy T Y; Wu, Winston Duo; Lin, Sean Xuqi; Chen, Xiao Dong; Chan, Peggy P Y

2011-07-15

Epigallocatechin gallate (EGCG) originated from green tea is well-known for its pharmaceutical potential and antiproliferating effect on carcinoma cells. For drug delivery, EGCG in a micro-/nanoparticle form is desirable for their optimized chemopreventive effect. In this study, first time reports that EGCG microparticles produced by low temperature spray drying can maintain high antioxidant activity. A monodisperse droplet generation system was used to realize the production of EGCG microparticles. EGCG microparticles were obtained with narrow size distribution and diameter of 30.24 ± 1.88 μM and 43.39 ± 0.69 μM for pure EGCG and lactose-added EGCG, respectively. The EC50 value (the amount of EGCG necessary to scavenge 50% of free radical in the medium) of spray dried pure EGCG particles obtained from different temperature is in the range of 3.029-3.075 μM compared to untreated EGCG with EC50 value of 3.028 μM. Varying the drying temperatures from 70°C and 130°C showed little detrimental effect on EGCG antioxidant activity. NMR spectrum demonstrated the EGCG did not undergo chemical structural change after spray drying. The major protective mechanism was considered to be: (1) the use of low temperature and (2) the heat loss from water evaporation that kept the particle temperature at low level. With further drier optimization, this monodisperse spray drying technique can be used as an efficient and economic approach to produce EGCG micro-/nanoparticles. Published by Elsevier B.V.

Quantification of antioxidants by using chlorpromazine hydrochloride: application of the method to food and medicinal plant samples.

PubMed

Nagaraja, Padmarajaiah; Aradhana, Narayanan; Suma, Aandamurthy; Shivakumar, Anantharaman; Chamaraja, Nelligere Arkeshwaraiah

2014-01-01

Chlorpromazine hydrochloride (CPH) (3-(2-chloro-phenothiazine-10-yl)-propyl] dimethylamine hydrochloride) has been the subject of a large number of studies employing a broad spectrum of oxidants, and chosen to examine the course of electron transfer reactions. We report on a method to determine the antioxidant activity of some food and medicinal plants using the oxidation of CPH by chromium(VI) to form a stable CPH radical in the 1:1 orthophosphoric acid-ethyl alcohol (OPA-EtOH) medium. The pink color of the control solution was measured at λ(max) of 530 nm. Nine standard antioxidants have been studied by this method, along with the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. The EC50, TEC50, antioxidant efficacy and the stoichiometric values for antioxidants have been evaluated. The radical scavenging activity expressed as EC50 ranged from 9.2 μg/mL in Camellia sinensis to 448.18 μg/mL in Cuminum cyminum. The application of a simple and versatile antioxidant capacity assay for dietary polyphenols and medicinal plant extracts, which are commonly used in Ayurveda opens its relevance in the field of antioxidant analysis.

Ca(2+)-stores mobilization by diadenosine tetraphosphate, Ap4A, through a putative P2Y purinoceptor in adrenal chromaffin cells.

PubMed Central

Castro, E.; Pintor, J.; Miras-Portugal, M. T.

1992-01-01

1. Diadenosine tetraphosphate (Ap4A) evoked a concentration-dependent increase in cytosolic [Ca2+] in resting chromaffin cells. The EC50 value for this action was 28.2 +/- 6.6 microM. This effect was also produced by diadenosine pentaphosphate (Ap5A) with an EC50 of 50 +/- 7 microM. 2. In contrast with this effect, pretreatment with Ap4A or Ap5A induced a 30% reduction in Ca2+ entry following 10 microM dimethylphenylpiperazinium. 3. The elevation in cytosolic [Ca2+] induced by Ap4A was persistent in approximately 100 nM external [Ca2+] and was sensitive to depletion of internal Ca2+ stores by a bradykinin prepulse or whole cell depletion in Ca2+. 4. The effect of Ap4A was mimicked and desensitized by the agonist adenosine 5'-O-(2-thiodiphosphate), and blocked by the P2Y-receptor antagonist, cibachrome blue. The P2X-receptor agonist alpha,beta-methylene adenosine 5'-triphosphate was inactive both by itself or in combination with Ap4A. This is compatible with a P2Y-purinoceptor-mediated action. PMID:1393282

Ca(2+)-stores mobilization by diadenosine tetraphosphate, Ap4A, through a putative P2Y purinoceptor in adrenal chromaffin cells.

PubMed

Castro, E; Pintor, J; Miras-Portugal, M T

1992-08-01

1. Diadenosine tetraphosphate (Ap4A) evoked a concentration-dependent increase in cytosolic [Ca2+] in resting chromaffin cells. The EC50 value for this action was 28.2 +/- 6.6 microM. This effect was also produced by diadenosine pentaphosphate (Ap5A) with an EC50 of 50 +/- 7 microM. 2. In contrast with this effect, pretreatment with Ap4A or Ap5A induced a 30% reduction in Ca2+ entry following 10 microM dimethylphenylpiperazinium. 3. The elevation in cytosolic [Ca2+] induced by Ap4A was persistent in approximately 100 nM external [Ca2+] and was sensitive to depletion of internal Ca2+ stores by a bradykinin prepulse or whole cell depletion in Ca2+. 4. The effect of Ap4A was mimicked and desensitized by the agonist adenosine 5'-O-(2-thiodiphosphate), and blocked by the P2Y-receptor antagonist, cibachrome blue. The P2X-receptor agonist alpha,beta-methylene adenosine 5'-triphosphate was inactive both by itself or in combination with Ap4A. This is compatible with a P2Y-purinoceptor-mediated action.

[Determination of the healing effect of Piper aduncum (spiked pepper or matico) on human fibroblasts].

PubMed

Paco, Karen; Ponce-Soto, Luis Alberto; Lopez-Ilasaca, Marco; Aguilar, José L

2016-01-01

To evaluate the healing effect of a Piper aduncum ethanol-water extract on an adult human dermal fibroblast cell line (hDFa). After obtaining the extract via solid-liquid extraction, concentration, and lyophilization, extract proteins were purified using reverse phase high-performance liquid chromatography, identified using tandem mass spectrometry of tryptic peptides, and analyzed using MALDI-TOF-TOF on an ABSciex4800 mass spectrometer. Half maximum effective concentration values (EC50), half maximum inhibiting concentration (IC50), and percentages of cell proliferation were determined using tetrazolium salt assays. Cell migration was evaluated using a "scratch assay". Growth factor expression in cells was analyzed via quantitative real-time reverse transcription polymerase chain reaction. Against the hDFa cell line, the extract had an IC50 of 200 μg/mL and EC50 of 103.5 µg/mL. In the proliferation assay, protein K2 (obtained from the extract) exhibited increased proliferative activity relative to other treatments (1 µg/mL); this agent also exhibited increased activity (50 µg/mL) in the fibroblast migration assay.Furthermore, the relative expression of platelet-derived growth factor increased by 8.6-fold in the presence of K2 protein relative to the control. The hydroethanolic extract of Piper aduncum and its component proteins increased the proliferation and migration of hDFa and increased the expression of growth factors involved in the healing process.

Muscarinic inhibition of [3H]-noradrenaline release on rabbit iris in vitro: effects of stimulation conditions on intrinsic activity of methacholine and pilocarpine.

PubMed Central

Bognar, I. T.; Pallas, S.; Fuder, H.; Muscholl, E.

1988-01-01

1. Rabbit isolated irides were loaded with [3H]-noradrenaline and superfused with Tyrode solution. The inhibition by the muscarinic agonists (+/-)-methacholine and pilocarpine of the [3H]-noradrenaline overflow into the superfusate evoked by field stimulation (pulses of 1 ms duration, 75 mA) was measured as an index of activation of presynaptic muscarinic receptors. 2. The fractional rate of release per pulse during the first stimulation period (S1) was low with 360 pulses at 3 Hz, intermediate with 360 pulses at 10 Hz and high with 1200 pulses at 10 Hz. Upon repetitive stimulation (7 periods at 20 min intervals), the fractional rates of release per pulse during S7 no longer differed, suggesting a 'long-term' regulation of [3H]-noradrenaline release depending on the stimulation conditions. 3. The evoked [3H]-noradrenaline overflow was depressed by (+/-)-methacholine in a concentration-dependent manner. The EC50 ranged from 0.29 to 0.42 microM. Methacholine nearly abolished the transmitter release evoked at 3 Hz but reduced that induced at 10 Hz by only 50%. Under the latter condition the methacholine concentration-inhibition curve was bell-shaped and no muscarinic inhibition was observed in the presence of methacholine 30 microM. After washout of methacholine the evoked [3H]-noradrenaline release was temporarily enhanced. 4. Atropine 0.1 microM enhanced the [3H]-noradrenaline overflow (evoked by stimulation with 360 or 1200 pulses at 10 Hz), probably antagonizing a presynaptic inhibition by endogenous acetylcholine. The inhibition by methacholine was competitively antagonized by atropine 0.1 microM (apparent -log KB = 8.5-9.0). 5. Depending on the concentration, pilocarpine reduced the [3H]-noradrenaline overflow evoked by 360 pulses at 3 Hz up to 63%. However, at 10 Hz stimulation frequency the compound was inactive as an agonist but competitively antagonized the presynaptic inhibition induced by methacholine. The KB under the latter condition (0.95 microM) was very close to the EC50 value determined at 3 Hz (0.85 microM). 6. The results demonstrate a muscarinic inhibition of noradrenaline release from the rabbit isolated iris. The activation by pilocarpine of the presynaptic receptors provides an alternative explanation for the miosis induced in the rabbit in vivo, which might be the result of a decreased sympathetic tone in the iris dilator muscle. PMID:3052680

The effect of magnesium sulfate concentration on the effective concentration of rocuronium, and sugammadex-mediated reversal, in isolated left phrenic nerve hemi-diaphragm preparations from the rat.

PubMed

Cho, Choon-Kyu; Sung, Tae-Yun; Choi, Seok-Jun; Choi, Hey-Ran; Kim, Yong Beom; Lee, Jung-Un; Yang, Hong-Seuk

2018-05-30

Perioperative magnesium sulfate (MgSO4) is used for analgesic, anti-arrhythmic, and obstetric purposes. The effects of MgSO4 on the neuromuscular blockade (NMB) induced by rocuronium, and the sugammadex reversal thereof, have not been clearly quantified. We investigated the effect increase concentrations of MgSO4 on the NMB by rocuronium, and sugammadex reversal, in isolated left phrenic nerve hemi-diaphragm (PNHD) preparations from the rat. Rat PNHD preparations were randomly allocated to one of four groups varying in terms of MgSO4 concentration (1, 2, 3, and 4 mM, each n = 10, in Krebs solution). The train-of-four (TOF) and twitch height responses were recorded mechanomyographically. The preparations were treated with incrementally increasing doses of rocuronium and each group's effective concentration (EC)50, EC90, and EC95 of rocuronium were calculated via nonlinear regression. Then, sugammadex was administered in doses equimolar to rocuronium. The recovery index, time to T1 height >95% of control, and the time to a TOF ratio (TOFR) >0.9 after sugammadex administration were measured. The EC50, EC90, and EC95 of rocuronium fell significantly as the magnesium level increased. The EC50, EC90, and EC95 of rocuronium did not differ between the 3 and 4 mM groups. The recovery index, time to T1 height >95% of control, and time to a TOFR >0.9 after sugammadex administration did not differ among the four groups. Increases in the magnesium concentration in rat PNHD preparations proportionally enhanced the NMB induced by rocuronium but did not affect reversal by equimolar amounts of sugammadex.

A comparative study on the relationship between various toxicological endpoints in Caenorhabditis elegans exposed to organophosphorus insecticides.

PubMed

Rajini, P S; Melstrom, Paul; Williams, Phillip L

2008-01-01

The toxicity of 10 organophophorus (OP) insecticides-acephate, dimethoate, dichlorvos, dicrotophos, monocrotophos, methamidophos, phosphamidon, omethoate, phosdrin, and trichlorfon-was evaluated in Caenorhabditis elegans using lethality, movement, and acetylcholinesterase (AChE) activity as the endpoints after a 4-hr- exposure period. The OP insecticides tested showed LC50 values ranging from 0.039 mM (for dichlorovs) to 472.8 mM (for methamidophos). The order of toxicity for lethality and movement was not significantly different when tested using the rank order correlation coefficient. AChE activity was markedly affected by all the OP insecticide exposures that caused significant inhibition in movement, indicating that the mechanism of toxicity of OP insecticides in C. elegans is the same as in higher animals. All OP insecticides induced greater than 50% inhibition of AChE at the lowest tested OP insecticide concentration resulting in inhibition in movement. While a significant correlation was evident between LC50 values in C. elegans and the LD50 values in rats for the 10 OP insecticides studied, a correlation was not evident between EC50 values in C. elegans and LD50 values in rats. Overall, the two endpoints, LC50 and movement, were more reliable and easier to perform than measurement of AChE activity in C. elegans for determining the toxicity of OP insecticides. Further, ranking of these endpoints with respect to the OP insecticides studied indicates that these parameters in C. elegans are predictive of OP insecticides mammalian neurotoxicity.

Spectroscopic characterization, antimicrobial activity and molecular docking study of novel azo-imine functionalized sulphamethoxazoles

NASA Astrophysics Data System (ADS)

Sahu, Nilima; Mondal, Sudipa; Naskar, Kaushik; Mahapatra, Ananya Das; Gupta, Suvroma; Slawin, Alexandra M. Z.; Chattopadhyay, Debprasad; Sinha, Chittaranjan

2018-03-01

[SMXsbnd Ndbnd Nsbnd C6H3sbnd (p-OH)(msbnd CHO)] (1) reacts with ArNH2 to synthesize Schiff bases, [SMXsbnd Ndbnd Nsbnd C6H3sbnd (psbnd OH)(msbnd HCdbnd Nsbnd Ar)] (Ar = sbnd C6H5 (2a), sbnd C6H4sbnd psbnd CH3 (2b), sbnd C6H4sbnd psbnd OCH3 (2c), sbnd C6H4sbnd psbnd Cl (2d), sbnd C6H4sbnd psbnd NO2 (2e), sbnd C10H7 (2f)) and the products have been assessed for antibacterial properties against Gram positive bacteria, B. subtillis: IC50 (μg/ml): 39.2 (1), 60.1 (2a), 64.0 (2b), 85.6 (2c), 55.1 (2d), 88.4 (2e) and 65.1 (2f); and Gram negative bacteria, E. coli: IC50 (μg/ml): 159.0 (1), 151.4 (2a), 155.3 (2b), 140 (2c), 156.0 (2d), 153.5 (2e) and 157 (2f). The cell line toxicity (Vero cells) has also been evaluated with these compounds and EC50 (μg/ml) values are 129.9 (1), 74.2 (2a) and 93.0 (2b), 191.9 (2c), 99.1 (2d), 93.2 (2e) and 62.0 (2f). The anti-viral efficiency against harpies virus (HSVsbnd 1F ATCC-733) infection demonstrates that the compound 1 has highest selectivity index (CC50/EC50), 5.06 than the compounds 2a-f (CC50/EC50: 1.18 (2a), 1.42 (2b), 3.50 (2c), 1.45 (2d), 1.58 (2e), 1.29 (2f)). The compounds have been spectroscopically characterized and the structural confirmation has been established in one case by single crystal X-ray diffraction studies of 2c. In silico Molecular Docking study has been done using optimized geometries of the compounds to search the most favored binding mode of these drugs and hence useful to explain their competitive drug efficiency.

Aluminium, gallium, and molybdenum toxicity to the tropical marine microalga Isochrysis galbana.

PubMed

Trenfield, Melanie A; van Dam, Joost W; Harford, Andrew J; Parry, David; Streten, Claire; Gibb, Karen; van Dam, Rick A

2015-08-01

There is a shortage of established chronic toxicity test methods for assessing the toxicity of contaminants to tropical marine organisms. The authors tested the suitability of the tropical microalga Isochrysis galbana for use in routine ecotoxicology and assessed the effects of 72-h exposures to copper (Cu, a reference toxicant), aluminium (Al), gallium (Ga), and molybdenum (Mo), key metals of alumina refinery discharge, on the growth of I. galbana at 3 temperatures: 24 °C, 28 °C, and 31 °C. The sensitivity of both I. galbana and the test method was validated by the response to Cu exposure, with 10% and 50% effect concentrations (EC10 and EC50) of 2.5 μg/L and 18 μg/L, respectively. The EC10 and EC50 values for total Al at 28 °C were 640 μg/L and 3045 μg/L, respectively. The toxicity of both Cu and Al at 24 °C and 31 °C was similar to that at 28 °C. There was no measurable toxicity from dissolved Ga exposures of up to 6000 μg/L or exposures to dissolved Mo of up to 9500 μg/L. Solubility limits at 28 °C for the dissolved fractions (<10 kDa) of Al, Ga, and Mo were approximately 650 μg/L Al, >7000 μg/L Ga, and >6000 μg/L Mo. In test solutions containing >650 μg/L total Al, dissolved and precipitated forms of Al were present, with precipitated Al becoming more dominant as total Al increased. The test method proved suitable for routine ecotoxicology, with I. galbana showing sensitivity to Cu but Al, Ga, and Mo exhibiting little to no toxicity to this species. © 2015 SETAC.

Using Amazon Web Services (AWS) to enable real-time, remote sensing of biophysical and anthropogenic conditions in green infrastructure systems in Philadelphia, an ultra-urban application of the Internet of Things (IoT)

NASA Astrophysics Data System (ADS)

Montalto, F. A.; Yu, Z.; Soldner, K.; Israel, A.; Fritch, M.; Kim, Y.; White, S.

2017-12-01

Urban stormwater utilities are increasingly using decentralized "green" infrastructure (GI) systems to capture stormwater and achieve compliance with regulations. Because environmental conditions, and design varies by GSI facility, monitoring of GSI systems under a range of conditions is essential. Conventional monitoring efforts can be costly because in-field data logging requires intense data transmission rates. The Internet of Things (IoT) can be used to more cost-effectively collect, store, and publish GSI monitoring data. Using 3G mobile networks, a cloud-based database was built on an Amazon Web Services (AWS) EC2 virtual machine to store and publish data collected with environmental sensors deployed in the field. This database can store multi-dimensional time series data, as well as photos and other observations logged by citizen scientists through a public engagement mobile app through a new Application Programming Interface (API). Also on the AWS EC2 virtual machine, a real-time QAQC flagging algorithm was developed to validate the sensor data streams.

Acute toxicity testing with the tropical marine copepod Acartia sinjiensis: optimisation and application.

PubMed

Gissi, F; Binet, M T; Adams, M S

2013-11-01

Globally there is limited toxicity data for tropical marine species, and there has been a call for further research and development in the area of tropical marine ecotoxicology. An increase in developmental pressures in northern tropical Australia is causing a higher demand for toxicity test protocols with ecologically relevant species. Copepods are a diverse group of zooplankton that are major components of marine food webs. The calanoid copepod Acartia sinjiensis is widely distributed across tropical and sub-tropical brackish to marine waters of Australia and was identified in a recent comprehensive review of marine tropical toxicity testing in Australia as a suitable test organism. Through a number of optimisation steps including feeding trials, changes to culture and test conditions; a 48-h acute toxicity test with A. sinjiensis was modified to become a highly reliable and reproducible standard test protocol. Control mobility was improved significantly, and the sensitivity of A. sinjiensis to copper (EC50 of 33µg/L), ammonia (EC50 of 10mg/L) and phenol (EC50 of 13mg/L) fell within the ranges of those reported previously, indicating that the modifications did not alter its sensitivity. In a comprehensive literature search we found that this species was the most sensitive to copper out of a range of marine copepods. The test was also successfully applied in toxicity assessments of four environmental samples: two produced formations waters (PFWs) and two mine tailing liquors (MTLs). The toxicity assessments utilised toxicity data from a suite of marine organisms (bacteria, microalgae, copepods, sea urchins, oysters, prawns, and fish). For the PFWs, which were predominantly contaminated with organic chemicals, A. sinjiensis was the most sensitive species (EC50 value 2-17 times lower than for any other test species). For the predominantly metal-contaminated mine tailing liquors, its sensitivity was similar to that of other test species used. The modified 48-h acute toxicity test with A. sinjiensis proved to be a valuable tool in these toxicity assessments, and is recommended for use in tropical marine toxicity assessments for northern Australia. Copyright © 2013 Elsevier Inc. All rights reserved.

Model based population PK-PD analysis of furosemide for BP lowering effect: A comparative study in primary and secondary hypertension.

PubMed

Shukla, Mahendra; Ibrahim, Moustafa M A; Jain, Moon; Jaiswal, Swati; Sharma, Abhisheak; Hanif, Kashif; Lal, Jawahar

2017-11-15

Though numerous reports have demonstrated multiple mechanisms by which furosemide can exert its anti-hypertensive response. However, lack of studies describing PK-PD relationship for furosemide featuring its anti-hypertensive property has limited its usage as a blood pressure (BP) lowering agent. Serum concentrations and mean arterial BP were monitored following 40 and 80mgkg -1 multiple oral dose of furosemide in spontaneously hypertensive rats (SHR) and DOCA-salt induced hypertensive (DOCA-salt) rats. A simultaneous population PK-PD relationship using E max model with effect compartment was developed to compare the anti-hypertensive efficacy of furosemide in these rat models. A two-compartment PK model with Weibull-type absorption and first-order elimination best described the serum concentration-time profile of furosemide. In the present study, post dose serum concentrations of furosemide were found to be lower than the EC 50 . The EC 50 predicted in DOCA-salt rats was found to be lower (4.5-fold), whereas the tolerance development was higher than that in SHR model. The PK-PD parameter estimates, particularly lower values of EC 50 , K e and Q in DOCA-salt rats as compared to SHR, pinpointed the higher BP lowering efficacy of furosemide in volume overload induced hypertensive conditions. Insignificantly altered serum creatinine and electrolyte levels indicated a favorable side effect profile of furosemide. In conclusion, the final PK-PD model described the data well and provides detailed insights into the use of furosemide as an anti-hypertensive agent. Copyright © 2017. Published by Elsevier B.V.

Polypharmacological profile of 1,2-dihydro-2-oxo-pyridine-3-carboxamides in the endocannabinoid system.

PubMed

Chicca, Andrea; Arena, Chiara; Bertini, Simone; Gado, Francesca; Ciaglia, Elena; Abate, Mario; Digiacomo, Maria; Lapillo, Margherita; Poli, Giulio; Bifulco, Maurizio; Macchia, Marco; Tuccinardi, Tiziano; Gertsch, Jürg; Manera, Clementina

2018-05-14

The endocannabinoid system (ECS) represents one of the major neuromodulatory systems involved in different physiological and pathological processes. Multi-target compounds exert their activities by acting via multiple mechanisms of action and represent a promising pharmacological modulation of the ECS. In this work we report 4-substituted and 4,5-disubstituted 1,2-dihydro-2-oxo-pyridine-3-carboxamide derivatives with a broad spectrum of affinity and functional activity towards both cannabinoid receptors and additional effects on the main components of the ECS. In particular compound B3 showed high affinity for CB1R (K i  = 23.1 nM, partial agonist) and CB2R (K i  = 6.9 nM, inverse agonist) and also significant inhibitory activity (IC 50  = 70 nM) on FAAH with moderate inhibition of ABHD12 (IC 50  = 2.5 μΜ). Compounds B4, B5 and B6 that act as full agonists at CB1R and as partial agonists (B5 and B6) or antagonist (B4) at CB2R, exhibited an additional multi-target property by inhibiting anandamide uptake with sub-micromolar IC 50 values (0.28-0.62 μΜ). The best derivatives showed cytotoxic activity on U937 lymphoblastoid cells. Finally, molecular docking analysis carried out on the three-dimensional structures of CB1R and CB2R and of FAAH allowed to rationalize the structure-activity relationships of this series of compounds. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Hydrophobic Tail Length, Degree of Fluorination and Headgroup Stereochemistry are Determinants of the Biocompatibility of (Fluorinated) Carbohydrate Surfactants

PubMed Central

Li, Xueshu; Turánek, Jaroslav; Knötigová, Pavlína; Kudláčková, Hana; Mašek, Josef; Parkin, Sean; Rankin, Stephen E; Knutson, Barbara L; Lehmler, Hans-Joachim

2009-01-01

A series of hydrocarbon and fluorocarbon carbohydrate surfactants with different headgroups (i.e., gluco-, galacto- and maltopyranoside) and (fluorinated) alkyl tails (i.e., C7 and C14 to C19) was synthesized to investigate trends in their cytotoxicity and haemolytic activity, and how surfactant-lipid interactions of selected surfactants contribute to these two measures of biocompatibility. All surfactants displayed low cytotoxicity (EC50 = 25 to > 250 μM) and low haemolytic activity (EC50 = 0.2 to > 3.3 mM), with headgroup structure, tail length and degree of fluorination being important structural determinants for both endpoints. The EC50 values of hydrocarbon and fluorocarbon glucopyranoside surfactants displayed a “cut-off” effect (i.e., a maximum with respect to the chain length). According to steady-state fluorescence anisotropy studies, short chain (C7) surfactants partitioned less readily into model membranes, which explains their low cytotoxicity and haemolytic activity. Interestingly, galactopyranosides were less toxic compared to glucopyranosides with the same hydrophobic tail. Although both surfactant types only differ in the stereochemistry of the 4-OH group, hexadecyl gluco- and galactopyranoside surfactants had similar apparent membrane partition coefficients, but differed in their overall effect on the phase behaviour of DPPC model membranes, as assessed using steady-state fluorescence anisotropy studies. These observations suggest that highly selective surfactant-lipid interactions may be responsible for the differential cytotoxicity and, possible, haemolytic activity of hydrocarbon and fluorocarbon carbohydrate surfactants intended for a variety of pharmaceutical and biomedical applications. PMID:19481909

Identification of Novel BACE1 Inhibitors by Combination of Pharmacophore Modeling, Structure-Based Design and In Vitro Assay.

PubMed

Ju, Yuan; Li, Zicheng; Deng, Yong; Tong, Aiping; Zhou, Liangxue; Luo, Youfu

2016-01-01

The protease β-secretase plays a critical role in the synthesis of pathogenic amyloid-β in Alzheimer's disease. In this study, pharmacophore constructed from receptor-ligand complex was used to screen Chemdiv and Zinc database and the resulting hits were subjected to docking experiments using LiandFit and CDOCKER programs. Molecules with high consensus scores and good interaction patterns in docking programs were retained. Drug-likeness assay including Lipinski's rule of five and ADMET properties filters were further used to identify BACE1 inhibitor. Finally, 13 compounds with novel scaffolds were selected and, considering of the nature of relative high LogP value of many marketed AD drugs, three of them with top 3 predicted LogP value were evaluated for their IC50 values in vitro by BACE1 enzymatic activity study. We believe that compound 13 with an IC50 value of 136 µM can be a lead compound with great potential in BACE1 inhibition and increasing activity by subsequently structure modification or optimization. At the same time, we found that the interaction between the residues Asp228, Asp32 of BACE1 and ligands is significant through analyzing the binding mode of 13 candidate compounds.

In Vitro Evaluation of the Impact of the Probiotic E. coli Nissle 1917 on Campylobacter jejuni's Invasion and Intracellular Survival in Human Colonic Cells.

PubMed

Helmy, Yosra A; Kassem, Issmat I; Kumar, Anand; Rajashekara, Gireesh

2017-01-01

Campylobacter jejuni is a leading cause of bacterial food poisoning in humans. Due to the rise in antibiotic-resistant Campylobacter , there exists a need to develop antibiotic-independent interventions to control infections in humans. Here, we evaluated the impact of Escherichia coli Nissle 1917 (EcN), a probiotic strain, on C. jejuni's invasion and intracellular survival in polarized human colonic cells (HT-29). To further understand how EcN mediates its impact, the expression of 84 genes associated with tight junctions and cell adhesion was profiled in HT-29 cells after treatment with EcN and challenge with C. jejuni . The pre-treatment of polarized HT-29 cells with EcN for 4 h showed a significant effect on C. jejuni 's invasion (∼2 log reduction) of the colonic cells. Furthermore, no intracellular C. jejuni were recovered from EcN pre-treated HT-29 cells at 24 h post-infection. Other probiotic strains tested had no significant impact on C. jejuni invasion and intracellular survival. C. jejuni decreased the expression of genes associated with epithelial cells permeability and barrier function in untreated HT-29 cells. However, EcN positively affected the expression of genes that are involved in enhanced intestinal barrier function, decreased cell permeability, and increased tight junction integrity. The results suggest that EcN impedes C. jejuni invasion and subsequent intracellular survival by affecting HT-29 cells barrier function and tight junction integrity. We conclude that EcN might be a viable alternative for controlling C. jejuni infections.

Exploration of diffuse and discrete sources of acid mine drainage to a headwater mountain stream in Colorado, USA

USGS Publications Warehouse

Johnston, Allison; Runkel, Robert L.; Navarre-Sitchler, Alexis; Singha, Kamini

2017-01-01

We investigated the impact of acid mine drainage (AMD) contamination from the Minnesota Mine, an inactive gold and silver mine, on Lion Creek, a headwater mountain stream near Empire, Colorado. The objective was to map the sources of AMD contamination, including discrete sources visible at the surface and diffuse inputs that were not readily apparent. This was achieved using geochemical sampling, in-stream and in-seep fluid electrical conductivity (EC) logging, and electrical resistivity imaging (ERI) of the subsurface. The low pH of the AMD-impacted water correlated to high fluid EC values that served as a target for the ERI. From ERI, we identified two likely sources of diffuse contamination entering the stream: (1) the subsurface extent of two seepage faces visible on the surface, and (2) rainfall runoff washing salts deposited on the streambank and in a tailings pile on the east bank of Lion Creek. Additionally, rainfall leaching through the tailings pile is a potential diffuse source of contamination if the subsurface beneath the tailings pile is hydraulically connected with the stream. In-stream fluid EC was lowest when stream discharge was highest in early summer and then increased throughout the summer as stream discharge decreased, indicating that the concentration of dissolved solids in the stream is largely controlled by mixing of groundwater and snowmelt. Total dissolved solids (TDS) load is greatest in early summer and displays a large diel signal. Identification of diffuse sources and variability in TDS load through time should allow for more targeted remediation options.

Modeling the near-ultraviolet band of GK stars. III. Dependence on abundance pattern

DOE Office of Scientific and Technical Information (OSTI.GOV)

Short, C. Ian; Campbell, Eamonn A., E-mail: ishort@ap.smu.ca

2013-06-01

We extend the grid of non-LTE (NLTE) models presented in Paper II to explore variations in abundance pattern in two ways: (1) the adoption of the Asplund et al. (GASS10) abundances, (2) for stars of metallicity, [M/H], of –0.5, the adoption of a non-solar enhancement of α-elements by +0.3 dex. Moreover, our grid of synthetic spectral energy distributions (SEDs) is interpolated to a finer numerical resolution in both T {sub eff} (ΔT {sub eff} = 25 K) and log g (Δlog g = 0.25). We compare the values of T {sub eff} and log g inferred from fitting LTE andmore » NLTE SEDs to observed SEDs throughout the entire visible band, and in an ad hoc 'blue' band. We compare our spectrophotometrically derived T {sub eff} values to a variety of T {sub eff} calibrations, including more empirical ones, drawn from the literature. For stars of solar metallicity, we find that the adoption of the GASS10 abundances lowers the inferred T {sub eff} value by 25-50 K for late-type giants, and NLTE models computed with the GASS10 abundances give T {sub eff} results that are marginally in better agreement with other T {sub eff} calibrations. For stars of [M/H] = –0.5 there is marginal evidence that adoption of α-enhancement further lowers the derived T {sub eff} value by 50 K. Stellar parameters inferred from fitting NLTE models to SEDs are more dependent than LTE models on the wavelength region being fitted, and we find that the effect depends on how heavily line blanketed the fitting region is, whether the fitting region is to the blue of the Wien peak of the star's SED, or both.« less

Fractal analysis of polyferric chloride-humic acid (PFC-HA) flocs in different topological spaces.

PubMed

Wang, Yili; Lu, Jia; Baiyu, Du; Shi, Baoyou; Wang, Dongsheng

2009-01-01

The fractal dimensions in different topological spaces of polyferric chloride-humic acid (PFC-HA) flocs, formed in flocculating different kinds of humic acids (HA) water at different initial pH (9.0, 7.0, 5.0) and PFC dosages, were calculated by effective density-maximum diameter, image analysis, and N2 absorption-desorption methods, respectively. The mass fractal dimensions (Df) of PFC-HA flocs were calculated by bi-logarithm relation of effective density with maximum diameter and Logan empirical equation. The Df value was more than 2.0 at initial pH of 7.0, which was 11% and 13% higher than those at pH 9.0 and 5.0, respectively, indicating the most compact flocs formed in flocculated HA water at initial pH of 7.0. The image analysis for those flocs indicates that after flocculating the HA water at initial pH greater than 7.0 with PFC flocculant, the fractal dimensions of D2 (logA vs. logdL) and D3 (logVsphere VS. logdL) of PFC-HA flocs decreased with the increase of PFC dosages, and PFC-HA flocs showed a gradually looser structure. At the optimum dosage of PFC, the D2 (logA vs. logdL) values of the flocs show 14%-43% difference with their corresponding Df, and they even had different tendency with the change of initial pH values. However, the D2 values of the flocs formed at three different initial pH in HA solution had a same tendency with the corresponding Dr. Based on fractal Frenkel-Halsey-Hill (FHH) adsorption and desorption equations, the pore surface fractal dimensions (Ds) for dried powders of PFC-HA flocs formed in HA water with initial pH 9.0 and 7.0 were all close to 2.9421, and the Ds values of flocs formed at initial pH 5.0 were less than 2.3746. It indicated that the pore surface fractal dimensions of PFC-HA flocs dried powder mainly show the irregularity from the mesopore-size distribution and marcopore-size distribution.

Correlation between 96-h mortality and 24-h acetylcholinesterase inhibition in three grass shrimp larval life stages.

PubMed

Key, Peter B; Fulton, Michael H

2006-03-01

Three life stages of larval grass shrimp were tested to determine whether acetylcholinesterase (AChE) activity expressed as 24-h sublethal effect endpoints (EC20 and EC50) could be used to predict 96-h mortality (lowest observable effect concentration (LOEC) and LC50) for shrimp exposed to three organophosphate insecticides. With regard to mortality, newly hatched larvae and 18-day-old larvae were the most sensitive in the malathion and azinphosmethyl exposures. In the chlorpyrifos exposures, newly hatched larvae and postlarvae were the most sensitive life stages. Results of the 24-h AChE inhibition tests showed that newly hatched larvae were generally more sensitive in the three organophosphate exposures. A regression analysis of the EC50's and LC50's yielded the strongest correlation with R2=0.987 (correlation coefficient=0.994 and 95% confidence intervals 0.969-0.999). The LOEC/EC20 relationship yielded R2=0.962. For these grass shrimp life stages and pesticides, sublethal effect endpoints could be used as a predictor of 96-h mortality.

Toxicity and genotoxicity of hospital laundry wastewaters treated with photocatalytic ozonation.

PubMed

Kern, Deivid I; Schwaickhardt, Rômulo de O; Mohr, Geane; Lobo, Eduardo A; Kist, Lourdes T; Machado, Ênio L

2013-01-15

The aim of the present study was to assess the efficiency of advanced oxidative processes based on photocatalytic ozonation (O(3), UV, UV/O(3), UV/O(3)/Fe(2+) 50 mg L(-1) and 150 mg L(-1)) in the treatment of hospital laundry wastewaters. The analysis of the investigated wastewater revealed high chemical oxygen demand (COD - 3343.8 mg L(-1)), biochemical oxygen demand (BOD(5) - 1906.4 mg L(-1)), total Kjeldahl nitrogen (TKN - 79.8 mg L(-1)) and Daphnia magna toxicity (EC50=1.73). Genotoxic effects were also detected for Allium cepa. Reductions of some parameters occurred after photocatalytic ozonation. The UV/O(3)/Fe(2+) 150 mg L(-1) method was more efficient in reducing COD (59.1%), BOD(5) (50.3%) and TKN (86.8%). There was significant reduction (p<0.05) in D. magna toxicity, O(3) (EC50=47.3%), UV (EC50=50.6%) and UV/O(3)/Fe(2+) 150 mg L(-1) (EC50=45.4%) processes. Normalization of the mitotic index and reduction of micronucleated cells were observed in A. cepa after the treatments. Results demonstrate that these methods were efficient in the degradation of hospital laundry wastewaters, representing a thriving alternative for the removal of pollutants that cause toxicity and genotoxicity. Copyright © 2012 Elsevier B.V. All rights reserved.

Lethal and sublethal endpoints observed for Artemia exposed to two reference toxicants and an ecotoxicological concern organic compound.

PubMed

Manfra, Loredana; Canepa, Sara; Piazza, Veronica; Faimali, Marco

2016-01-01

Swimming speed alteration and mortality assays with the marine crustacean Artemia franciscana were carried out. EC50 and LC50 values after 24-48h exposures were calculated for two reference toxicants, copper sulphate pentahydrate (CuSO4·5H2O) and Sodium Dodecyl Sulphate (SDS), and an ecotoxicological concern organic compound, Diethylene Glycol (DEG). Different end-points have been evaluated, in order to point out their sensitivity levels. The swimming speed alteration (SSA) was compared to mortality values and also to the hatching rate inhibition (literature data). SSA resulted to be more sensitive than the mortality and with a sensitivity comparable to (or even higher than) the hatching rate endpoint. Copyright © 2015 Elsevier Inc. All rights reserved.

Discovery of piperidin-4-yl-aminopyrimidine derivatives as potent non-nucleoside HIV-1 reverse transcriptase inhibitors.

PubMed

Wan, Zheng-Yong; Yao, Jin; Tao, Yuan; Mao, Tian-Qi; Wang, Xin-Long; Lu, Yi-Pei; Wang, Hai-Feng; Yin, Hong; Wu, Yan; Chen, Fen-Er; De Clercq, Erik; Daelemans, Dirk; Pannecouque, Christophe

2015-06-05

A novel series of piperidin-4-yl-aminopyrimidine derivatives were designed fusing the pharmacophore templates of etravirine-VRX-480773 hybrids our group previously described and piperidine-linked aminopyrimidines. Most compounds displayed significantly improved activity against wild-type HIV-1 with EC50 values in single-digit nanomolar concentrations compared to etravirine-VRX-480773 hybrids. Selected compounds were also evaluated for activity against reverse transcriptase, and had lower IC50 values than that of nevirapine. The improved potency observed in this in vitro model of HIV RNA replication partly validates the mechanism by which this class of allosteric pyrimidine derivatives inhibits reverse transcriptase, and represents a remarkable step forward in the development of AIDS therapeutics. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Direct comparison of oligochaete erythrocruorins as potential blood substitutes

PubMed Central

Zimmerman, Devon; DiIusto, Matthew; Dienes, Jack; Abdulmalik, Osheiza

2017-01-01

Abstract While many blood substitutes are based on mammalian hemoglobins (e.g., human hemoglobin, HbA), the naturally extracellular hemoglobins of invertebrates (a.k.a. erythrocruorins, Ecs) are intriguing alternative oxygen carriers. Specifically, the erythrocruorin of Lumbricus terrestris has been shown to effectively deliver oxygen in mice and rats without the negative side effects observed with HbA. In this study, the properties of six oligochaete Ecs (Lumbricus terrestris, Eisenia hortensis, Eisenia fetida, Eisenia veneta, Eudrilus eugeniae, and Amynthas gracilis) were compared in vitro to identify the most promising blood substitute candidate(s). Several metrics were used to compare the Ecs, including their oxidation rates, dissociation at physiological pH, thermal stability, and oxygen transport characteristics. Overall, the Ecs of Lumbricus terrestris (LtEc) and Eisenia fetida (EfEc) were identified as promising candidates, since they demonstrated high thermal and oligomeric stability, while also exhibiting relatively low oxidation rates. Interestingly, the O2 affinity of LtEc (P 50 = 26.25 mmHg at 37 °C) was also observed to be uniquely lower than EfEc and all of the other Ecs (P 50 = 9.29–13.62 mmHg). Subsequent alignment of the primary sequences of LtEc and EfEc revealed several significant amino acid substitutions within the D subunit interfaces that may be responsible for this significant change in O2 affinity. Nonetheless, these results show that LtEc and EfEc are promising potential blood substitutes that are resistant to oxidation and denaturation, but additional experiments will need to be conducted to determine their safety, efficacy, and the effects of their disparate oxygen affinities in vivo. PMID:29313031

Water analysis via portable X-ray fluorescence spectrometry

NASA Astrophysics Data System (ADS)

Pearson, Delaina; Chakraborty, Somsubhra; Duda, Bogdan; Li, Bin; Weindorf, David C.; Deb, Shovik; Brevik, Eric; Ray, D. P.

2017-01-01

Rapid, in-situ elemental water analysis would be an invaluable tool in studying polluted and/or salt-impacted waters. Analysis of water salinity has commonly used electrical conductance (EC); however, the identity of the elements responsible for the salinity are not revealed using EC. Several studies have established the viability of using portable X-ray fluorescence (PXRF) spectrometry for elemental data analysis of soil, sediment, and other matrices. However, the accuracy of PXRF is known to be affected while scanning moisture-laden soil samples. This study used PXRF elemental data in water samples to predict water EC. A total of 256 water samples, from 10 different countries were collected and analyzed via PXRF, inductively coupled plasma atomic emission spectroscopy (ICP-AES), and a digital salinity bridge. The PXRF detected some elements more effectively than others, but overall results indicated that PXRF can successfully predict water EC via quantifying Cl in water samples (validation R2 and RMSE of 0.77 and 0.95 log μS cm-1, respectively). The findings of this study elucidated the potential of PXRF for future analysis of pollutant and/or metal contaminated waters.

Nutritional, Biophysical and Physiological Characteristics of Wild Rocket Genotypes As Affected by Soilless Cultivation System, Salinity Level of Nutrient Solution and Growing Period

PubMed Central

Bonasia, Anna; Lazzizera, Corrado; Elia, Antonio; Conversa, Giulia

2017-01-01

With the aim of defining the best management of nutrient solution (NS) in a soilless system for obtaining high quality baby-leaf rocket, the present study focuses on two wild rocket genotypes (“Nature” and “Naturelle”), grown in a greenhouse under two Southern Italy growing conditions—autumn-winter (AW) and winter-spring (WS)—using two soilless cultivation systems (SCS)—at two electrical conductivity values (EC) of NS. The SCSs used were the Floating System (FS) and Ebb and Flow System (EFS) and the EC values were 2.5 and 3.5 dS m−1 (EC2.5; EC3.5) for the AW cycle and 3.5 and 4.5 dS m−1 (EC3.5; EC4.5) for the WS cycle. The yield, bio-physical, physiological and nutritional characteristics were evaluated. Higher fresh (FY) (2.25 vs. 1.50 kg m−2) and dry (DY) (230.6 vs. 106.1 g m−2) weight yield, leaf firmness (dry matter, 104.3 vs. 83.2 g kg−1 FW; specific leaf area, 34.8 vs. 24.2 g cm−2) and antioxidant compounds (vitamin C, 239.0 vs. 152.7 mg kg−1 FW; total phenols, 997 vs. 450 mg GAE mg kg−1 FW; total glucosinulates-GLSs, 1,078.8 vs. 405.7 mg kg−1 DW; total antioxidant capacity-TAC, 11,534 vs. 8,637 μmol eq trolox kg−1 FW) and lower nitrates (1,470 vs. 3,460 mg kg−1 FW) were obtained under WS conditions. The seasonal differences were evident on the GLS profile: some aliphatic GLSs (gluconapoleiferin, glucobrassicanapin) and indolic 4-OH-glucobrassicin were only expressed in WS conditions, while indolic glucobrassicin was only detected in the AW period. Compared with EFS, FS improved leaf firmness, visual quality, antioxidant content (TAC, +11.6%) and reduced nitrate leaf accumulation (−37%). “Naturelle” performed better than “Nature” in terms of yield, visual quality and nutritional profile, with differences more evident under less favorable climatic conditions and when the cultivars were grown in FS. Compared to EC2.5, the EC3.5 treatment did not affect DY while enhancing firmness, visual quality, and antioxidant compounds (TAC, +8%), and reducing the nitrate content (−47%). The EC4.5 treatment reduced FY and DY and the antioxidant content. Despite seasonal climatic condition variability, FS and the moderate salinity level of NS (3.5 dS m−1) can be suggested as optimum. PMID:28337211

Nutritional, Biophysical and Physiological Characteristics of Wild Rocket Genotypes As Affected by Soilless Cultivation System, Salinity Level of Nutrient Solution and Growing Period.

PubMed

Bonasia, Anna; Lazzizera, Corrado; Elia, Antonio; Conversa, Giulia

2017-01-01

With the aim of defining the best management of nutrient solution (NS) in a soilless system for obtaining high quality baby-leaf rocket, the present study focuses on two wild rocket genotypes ("Nature" and "Naturelle"), grown in a greenhouse under two Southern Italy growing conditions-autumn-winter (AW) and winter-spring (WS)-using two soilless cultivation systems (SCS)-at two electrical conductivity values (EC) of NS. The SCSs used were the Floating System (FS) and Ebb and Flow System (EFS) and the EC values were 2.5 and 3.5 dS m -1 (EC2.5; EC3.5) for the AW cycle and 3.5 and 4.5 dS m -1 (EC3.5; EC4.5) for the WS cycle. The yield, bio-physical, physiological and nutritional characteristics were evaluated. Higher fresh (FY) (2.25 vs. 1.50 kg m -2 ) and dry (DY) (230.6 vs. 106.1 g m -2 ) weight yield, leaf firmness (dry matter, 104.3 vs. 83.2 g kg -1 FW; specific leaf area, 34.8 vs. 24.2 g cm -2 ) and antioxidant compounds (vitamin C, 239.0 vs. 152.7 mg kg -1 FW; total phenols, 997 vs. 450 mg GAE mg kg -1 FW; total glucosinulates-GLSs, 1,078.8 vs. 405.7 mg kg -1 DW; total antioxidant capacity-TAC, 11,534 vs. 8,637 μmol eq trolox kg -1 FW) and lower nitrates (1,470 vs. 3,460 mg kg -1 FW) were obtained under WS conditions. The seasonal differences were evident on the GLS profile: some aliphatic GLSs (gluconapoleiferin, glucobrassicanapin) and indolic 4-OH-glucobrassicin were only expressed in WS conditions, while indolic glucobrassicin was only detected in the AW period. Compared with EFS, FS improved leaf firmness, visual quality, antioxidant content (TAC, +11.6%) and reduced nitrate leaf accumulation (-37%). "Naturelle" performed better than "Nature" in terms of yield, visual quality and nutritional profile, with differences more evident under less favorable climatic conditions and when the cultivars were grown in FS. Compared to EC2.5, the EC3.5 treatment did not affect DY while enhancing firmness, visual quality, and antioxidant compounds (TAC, +8%), and reducing the nitrate content (-47%). The EC4.5 treatment reduced FY and DY and the antioxidant content. Despite seasonal climatic condition variability, FS and the moderate salinity level of NS (3.5 dS m -1 ) can be suggested as optimum.

Enhanced encapsulation of metoprolol tartrate with carbon nanotubes as adsorbent

NASA Astrophysics Data System (ADS)

Garala, Kevin; Patel, Jaydeep; Patel, Anjali; Dharamsi, Abhay

2011-12-01

A highly water-soluble antihypertensive drug, metoprolol tartrate (MT), was selected as a model drug for preparation of multi-walled carbon nanotubes (MWCNTs)-impregnated ethyl cellulose (EC) microspheres. The present investigation was aimed to increase encapsulation efficiency of MT with excellent adsorbent properties of MWCNTs. The unique surface area, stiffness, strength and resilience of MWCNTs have drawn much anticipation as carrier for highly water-soluble drugs. Carbon nanotubes drug adsorbate (MWCNTs:MT)-loaded EC microspheres were further optimized by the central composite design of the experiment. The effects of independent variables (MWCNTs:MT and EC:adsorbate) were evaluated on responses like entrapment efficiency (EE) and t 50 (time required for 50% drug release). The optimized batch was compared with drug alone EC microspheres. The results revealed high degree of improvement in encapsulation efficiency for MWCNTs:MT-loaded EC microspheres. In vitro drug release study exhibited complete release form drug alone microspheres within 15 h, while by the same time only 50-60% drug was released for MWCNTs-impregnated EC microspheres. The optimized batch was further characterized by various instrumental analyses such as scanning electron microscopy, powder X-ray diffraction and differential scanning calorimetry. The results endorse encapsulation of MWCNTs:MT adsorbate inside the matrix of EC microspheres, which might have resulted in enhanced encapsulation and sustained effect of MT. Hence, MWCNTs can be utilized as novel carriers for extended drug release and enhanced encapsulation of highly water-soluble drug, MT.

Monitoring the ecotoxicity of γ-Al2O3 and Ni/γ-Al2O3 nanomaterials by means of a battery of bioassays.

PubMed

Svartz, Gabriela; Papa, Mariana; Gosatti, Marina; Jordán, Marianela; Soldati, Analia; Samter, Paula; Guraya, María M; Pérez Coll, Cristina; Perez Catán, Soledad

2017-10-01

The increasing application of nanoparticles (NPs) to a variety of new technologies has become a matter of concern due to the potential toxicity of these materials. Many questions about the fate of NPs in the environment and the subsequent impact on ecosystems need to be answered. The aim of this work was to evaluate the ecotoxicity of two alumina-based nanoceramics, γ-Al2O3 (NC) and Ni/ γ-Al2O3 (NiNC) by means of three different standardized tests: Biochemical Oxygen Demand (BOD5), bioassay with luminescent bacteria (Vibrio fischeri; Microtox), and bioassay on amphibian larvae (Rhinella arenarum) (AMPHITOX). BOD5 values of a very biodegradable mixture (glucose/glutamic acid) decreased with the addition of NiNC(43.8%) and NC (31.6%) with respect to control samples (52.9%). Microtox test results indicated that NiNC presents higher toxicity than NC, with EC50s values of 16.1% and 29.9% respectively; a reduced toxicity was observed, however, in presence of organic matter, thus obtaining EC50s of 37.8% and 19.4%. The results of AMPHITOX test showed a significant increase in the toxicity of both substances over time, the NiNC toxicity being greater than that of NC. The values of 96h-LC50 and 504h-LC50 determined for NiNC were 1.58 and 0.83mg/L, respectively, and 14.5 and 10.5mg/L for NC samples. Amphibian larvae exhibited collapsed cavities, edema, axial flexures, and behavioral alterations as hyperkinesia and reduced movements. These results evidence the vulnerability of wildlife to xenobiotics and the need to develop specific standardized ecotoxicity tests in order to help environmental sustainability and natural species conservation. Copyright © 2017. Published by Elsevier Inc.

Temperature influences the toxicity of deltamethrin, chlorpyrifos and dimethoate to the predatory mite Hypoaspis aculeifer (Acari) and the springtail Folsomia candida (Collembola).

PubMed

Jegede, O O; Owojori, O J; Römbke, J

2017-06-01

In order to assess the influence of temperature on pesticide toxicity to soil fauna, specimens of the predatory mite Hypoaspis aculeifer and the springtail Folsomia candida were exposed in artificial soil spiked with different concentrations of three pesticides (dimethoate, chlorpyrifos and deltamethrin) at 20°C vs 28°C for the mites and 20°C vs 26°C for the springtails. All tests were carried out according to OECD guidelines. In the mite tests, the toxic effects of dimethoate and chlorpyrifos on survival was about two orders of magnitude more at 28°C than at 20°C. Mite reproduction decreased in the tests with chlorpyrifos and deltamethrin by about four to five orders of magnitude at 28°C than at 20°C. (EC50 28 ° C =1.42 and 2.52mg/kg vs EC50 20 ° C =6.18 and 10.09mg/kg) In the collembolan tests, the toxicity of dimethoate on survival was higher at 26°C than at 20°C (LC50 26 ° C =0.17mg/kg vs LC50 20 ° C =0.36mg/kg), while the opposite was detected for deltamethrin (LC50 26 ° C =11.27mg/kg vs LC50 20 ° C =6.84mg/kg). No difference was found in the test with chlorpyrifos. Effects of dimethoate and chlorpyrifos on reproduction were higher at 26°C than at 20°C (EC50 26 ° C =0.11 and 0.018mg/kg vs EC50 20 ° C =0.29 and 0.031mg/kg respectively), but in the case of deltamethrin the opposite was observed (EC50 26 ° C =12.85mg/kg vs EC50 20 ° C =2.77mg/kg). A preliminary risk assessment of the three pesticides at the two temperature regimes based on the Toxicity Exposure Ratio (TER) approach of the European Union, shows that in general there are few different outcomes when comparing data gained at different temperatures. However, in the light of the few comparisons made data gained in temperate regions should be used with caution in the tropics. Copyright © 2017 Elsevier Inc. All rights reserved.

Prostaglandins mediate the stimulatory effects of endothelin-1 on cAMP accumulation and inositol-1,4,5-trisphosphate production and contraction in cat iris sphincter.

PubMed

Yousufzai, S Y; Ye, Z; Abdel-Latif, A A

1995-12-01

We previously reported that in the iris sphincter smooth muscle, endothelin-1 (ET-1) activates both adenylyl cyclase and the phosphoinositide cascade and that the changes in the levels of cAMP and inositol-1,4,5-trisphosphate (IP3) produced are species specific. In the present study, we examined the mechanism of the ET-1 effects in cat iris sphincter. In general, we found that ET-1 (0.1 microM) increased prostaglandin E2 (PGE2) release by 156%, cAMP accumulation by 310%, IP3 production by 88% and induced contraction; that PGE2 increased cAMP accumulation, IP3 production and contraction; and that the effects of ET-1 are inhibited by indomethacin (Indo), suggesting that arachidonic acid metabolites may mediate the responses to the peptide. Kinetic studies revealed the following: (1) The effect of ET-1 on cAMP accumulation is rapid (within 30 sec), dose dependent (EC50 = 5.8 nM) and completely abolished by Indo (Ki = 0.16 microM), a cyclooxygenase inhibitor, but not by nordihydroguairetic acid, a lipoxygenase inhibitor, implying the involvement of PGs. (2) ET-1 dose-dependently evoked PGe2 release (EC50 = 1.8 nM), IP3 production (EC50 = 4.5 nM) and contraction (EC50 = 5 nM) and that all of these responses were inhibited by Indo. (3) PGE2 increased cAMP accumulation in a dose-dependent manner with an EC50 of 1.5 x 10(-7) M, and PGD2 and PGF2 alpha had little effect on the cyclic nucleotide. (4) PGE2 (1 microM), increased IP3 production by 55% and induced muscle contraction in a dose-dependent manner (EC50 = 40 nM). We conclude from these data that in cat iris sphincter PGs may mediate ET-1-induced cAMP accumulation, IP3 production and smooth muscle contraction.

Use of biopartitioning micellar chromatography and RP-HPLC for the determination of blood-brain barrier penetration of α-adrenergic/imidazoline receptor ligands, and QSPR analysis.

PubMed

Vucicevic, J; Popovic, M; Nikolic, K; Filipic, S; Obradovic, D; Agbaba, D

2017-03-01

For this study, 31 compounds, including 16 imidazoline/α-adrenergic receptor (IRs/α-ARs) ligands and 15 central nervous system (CNS) drugs, were characterized in terms of the retention factors (k) obtained using biopartitioning micellar and classical reversed phase chromatography (log k BMC and log k wRP , respectively). Based on the retention factor (log k wRP ) and slope of the linear curve (S) the isocratic parameter (φ 0 ) was calculated. Obtained retention factors were correlated with experimental log BB values for the group of examined compounds. High correlations were obtained between logarithm of biopartitioning micellar chromatography (BMC) retention factor and effective permeability (r(log k BMC /log BB): 0.77), while for RP-HPLC system the correlations were lower (r(log k wRP /log BB): 0.58; r(S/log BB): -0.50; r(φ 0 /P e ): 0.61). Based on the log k BMC retention data and calculated molecular parameters of the examined compounds, quantitative structure-permeability relationship (QSPR) models were developed using partial least squares, stepwise multiple linear regression, support vector machine and artificial neural network methodologies. A high degree of structural diversity of the analysed IRs/α-ARs ligands and CNS drugs provides wide applicability domain of the QSPR models for estimation of blood-brain barrier penetration of the related compounds.

Comparison of wet-only and bulk deposition at Chiang Mai (Thailand) based on rainwater chemical composition

NASA Astrophysics Data System (ADS)

Chantara, Somporn; Chunsuk, Nawarut

The chemical composition of 122 rainwater samples collected daily from bulk and wet-only collectors in a sub-urban area of Chiang Mai (Thailand) during August 2005-July 2006 has been analyzed and compared to assess usability of a cheaper and less complex bulk collector over a sophisticated wet-only collector. Statistical analysis was performed on log-transformed daily rain amount and depositions of major ions for each collector type. The analysis of variance (ANOVA) test revealed that the amount of rainfall collected from a rain gauge, bulk collector and wet-only collector showed no significant difference ( ∝=0.05). The volume weight mean electro-conductivity (EC) values of bulk and wet-only samples were 0.69 and 0.65 mS/m, respectively. The average pH of the samples from both types of collectors was 5.5. Scatter plots between log-transformed depositions of specific ions obtained from bulk and wet-only samples showed high correlation ( r>0.91). Means of log-transformed bulk deposition were 14% (Na + and K +), 13% (Mg 2+), 7% (Ca 2+), 4% (NO 3-), 3% (SO 42- and Cl -) and 2% (NH 4+) higher than that of wet-only deposition. However, multivariate analysis of variance (MANOVA) revealed that ion depositions obtained from bulk and wet-only collectors were not significantly different ( ∝=0.05). Therefore, it was concluded that a bulk collector can be used instead of a wet-only collector in a sub-urban area.

Peracetic acid (PAA) disinfection of primary, secondary and tertiary treated municipal wastewaters.

PubMed

Koivunen, J; Heinonen-Tanski, H

2005-11-01

The efficiency of peracetic acid (PAA) disinfection against enteric bacteria and viruses in municipal wastewaters was studied in pilot-scale. Disinfection pilot-plant was fed with the primary or secondary effluent of Kuopio municipal wastewater treatment plant or tertiary effluent from the pilot-scale dissolved air flotation (DAF) unit. Disinfectant doses ranged from 2 to 7 mg/l PAA in the secondary and tertiary effluents, and from 5 to 15 mg/l PAA in the primary effluents. Disinfection contact times were 4-27 min. Disinfection of secondary and tertiary effluents with 2-7 mg/l PAA and 27 min contact time achieved around 3 log reductions of total coliforms (TC) and enterococci (EC). PAA disinfection also significantly improved the hygienic quality of the primary effluents: 10-15 mg/l PAA achieved 3-4 log reductions of TC and EC, 5 mg/l PAA resulting in below 2 log reductions. F-RNA coliphages were more resistant against the PAA disinfection and around 1 log reductions of these enteric viruses were typically achieved in the disinfection treatments of the primary, secondary and tertiary effluents. Most of the microbial reductions occurred during the first 4-18 min of contact time, depending on the PAA dose and microorganism. The PAA disinfection efficiency remained relatively constant in the secondary and tertiary effluents, despite of small changes of wastewater quality (COD, SS, turbidity, 253.7 nm transmittance) or temperature. The disinfection efficiency clearly decreased in the primary effluents with substantially higher microbial, organic matter and suspended solids concentrations. The results demonstrated that PAA could be a good alternative disinfection method for elimination of enteric microbes from different wastewaters.

Bacteriological quality of drinking water in the Atebubu-Amantin District of the Brong-Ahafo Region of Ghana

NASA Astrophysics Data System (ADS)

Tekpor, M.; Akrong, M. O.; Asmah, M. H.; Banu, R. A.; Ansa, E. D. O.

2017-09-01

The study was carried out to determine the bacteriological safety of water in hand-dug wells in the Atebubu-Amantin District of the Brong-Ahafo Region in Ghana. A total of 60 samples were collected from ten hand dug wells and analysed for total coliform (TC), faecal coliform (FC), E. coli (EC), Salmonella spp. (SP) and Enterococcus spp. (ES). Data was collected in both the rainy and the dry seasons. The results obtained showed that water from all the wells in the study area did not meet the World Health Organisation guideline and Ghana standard for drinking water of zero (0) coliform forming unit (cfu) per 100 ml for TC, FC, EC, SP and ES, respectively. Contamination was found to be high in the wells during the wet season as compared to the dry season. Wells (A1 to A5) which were close to septic tanks had high bacteria counts in both seasons. The total coliform counts ranged from 2.98 to 5.93 log cfu/100 ml in the wet season and 3.10-5.03 log cfu/100 ml in the dry season. There was drastic reduction of faecal coliform count from a range of 2.78-4.55 log cfu/100 ml in the wet season to 1.70-3.51 log cfu/100 ml in the dry season. The high bacteria count in wells A1 to A5 could be attributed to the closeness of the wells to the septic tank, and contaminant transport through the saturated underground zones. It is recommended that the water should be treated properly before drinking.

Persea americana Glycolic Extract: In Vitro Study of Antimicrobial Activity against Candida albicans Biofilm and Cytotoxicity Evaluation.

PubMed

Jesus, D; Oliveira, J R; Oliveira, F E; Higa, K C; Junqueira, J C; Jorge, A O C; Back-Brito, G N; Oliveira, L D

2015-01-01

This study evaluated the antifungal activity of Persea americana extract on Candida albicans biofilm and its cytotoxicity in macrophage culture (RAW 264.7). To determine the minimum inhibitory concentration (MIC), microdilution in broth (CLSI M27-S4 protocol) was performed. Thereafter, the concentrations of 12.5, 25, 50, 100, and 200 mg/mL (n = 10) with 5 min exposure were analyzed on mature biofilm in microplate wells for 48 h. Saline was used as control (n = 10). After treatment, biofilm cells were scraped off and dilutions were plated on Sabouraud dextrose agar. After incubation (37°C/48 h), the values of colony forming units per milliliter (CFU/mL) were converted to log10 and analyzed (ANOVA and Tukey test, 5%). The cytotoxicity of the P. americana extract was evaluated on macrophages by MTT assay. The MIC of the extract was 6.25 mg/mL and with 12.5 mg/mL there was elimination of 100% of planktonic cultures. Regarding the biofilms, a significant reduction (P < 0.001) of the biofilm at concentrations of 50 (0.580 ± 0.209 log10), 100 (0.998 ± 0.508 log10), and 200 mg/mL (1.093 ± 0.462 log10) was observed. The concentrations of 200 and 100 mg/mL were cytotoxic for macrophages, while the concentrations of 50, 25, and 12.5 mg/mL showed viability higher than 55%.

Design, synthesis and biological evaluation of novel ring-opened cromakalim analogues with relaxant effects on vascular and respiratory smooth muscles and as stimulators of elastin synthesis.

PubMed

Bouhedja, Mourad; Peres, Basile; Fhayli, Wassim; Ghandour, Zeinab; Boumendjel, Ahcène; Faury, Gilles; Khelili, Smail

2018-01-20

Two new series of ring-opened analogues of cromakalim bearing sulfonylurea moieties (series A: with N-unmethylated sulfonylureas, series B: with N-methylated sulfonylureas) were synthesized and tested as relaxants of vascular and respiratory smooth muscles (rat aorta and trachea, respectively). Ex vivo biological evaluations indicated that the most active compounds, belonging to series B, displayed a marked vasorelaxant activity on endothelium-intact aortic rings and the trachea. A majority of series B compounds exhibited a higher vasorelaxant activity (EC 50  < 22 μM) than that of the reference compound diazoxide (EC 50  = 24 μM). Interestingly, several tested compounds of series B also presented stronger relaxant effects on the trachea than the reference compound cromakalim (EC 50  = 124 μM), in particular compounds B4, B7 and B16 (EC 50  < 10 μM). By contrast, series A derivatives were poorly active on aortic rings (EC 50  > 57 μM for all, and EC 50  > 200 μM for a majority of them), but some of them showed an interesting relaxing effect on trachea (i.e. A15 and A33, EC 50  = 30 μM). The most potent compounds of both series, i.e. A15, A33 and B16, tested on aortic rings in the presence of glibenclamide or 80 mM KCl, suggested that they acted as voltage-gated Ca 2+ channel blockers, like verapamil, instead of being ATP-potassium channel activators, as is cromakalim, the parent molecule. Further investigations on cultured vascular smooth muscle cells showed a strong stimulating effect on elastin synthesis, especially compound B16, which was more active at 20 μM than diazoxide, a reference ATP-sensitive potassium channel activator. Taken together, our results show that the N-methylation of the sulfonylurea moieties of ring-opened cromakalim analogues led to new compounds blocking calcium-gated channels, which had a major impact on the arterial and tracheal activities as well as selectivity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Comparative sensitivity of juvenile and adult Potamopyrgus antipodarum (Mollusca: Hydrobiidae) under chronic exposure to cadmium and tributyltin.

PubMed

Ruppert, Katharina; Geiß, Cornelia; Ostermann, Sina; Theis, Christina; Oehlmann, Jörg

2016-07-28

To investigate a potential extension of a partial life cycle test protocol to a full life cycle test design, a comparative sensitivity analysis with juvenile and adult Potamopyrgus antipodarum was performed. Neonates and adult snails were exposed to the metal cadmium (Cd) and the endocrine disruptor tributyltin (TBT) at nominal concentrations ranging from 1.56 to 50 μg Cd/L and from 25 to 1,000 ng TBT-Sn/L. The experiments were performed over 28 days at 16°C in a semi-static test design. Mortality was assessed for both life stages. Juvenile snails' specific growth rate and reproduction of adults were investigated as main endpoints. We determined effects on snails' survival, juvenile growth and embryo numbers in the brood pouch of adult snails under exposure to both chemicals. Juvenile control mortality was between 25% and 30% and significantly higher than in the control groups with adult snails. A higher sensitivity of juvenile snails compared to adults was observed for the endpoint mortality. Calculated LC50 in Cd exposed snails was 38.2 μg/L for adults and 15.0 μg/L for juvenile snails. Significant effects on mortality in TBT exposed adult snails occurred at the highest test concentration only with a LC50 of 535 ng Sn/L. Juvenile survival was significantly affected at 50.8 ng Sn/L and higher concentrations. Effect concentrations for the main endpoints reproduction and juvenile growth show comparable sensitivities. For Cd exposed groups, EC50 values were 11.3 μg/L for the endpoint reproduction in adult snails and 3.82 μg/L for juvenile growth with overlapping confidence intervals. TBT also significantly affected juvenile snails' growth (EC50: 178 ng Sn /L). EC50 for embryo numbers was 125 ng TBT-Sn/L. Results indicate the manageability of a FLC test starting with newly hatched snails. Precautions have to be taken to guarantee a sufficient number of surviving snails until adulthood so that reproduction can be assessed. For final decision for the practicability of a FLC, further tests are needed.

Influence of standard and novel LTB4 analogs on human neutrophil chemotaxis measured by the multiwell cap assay.

PubMed

Psychoyos, S; Uziel-Fusi, S; Bhagwat, S; Morrissey, M M

1989-11-30

Standard and novel LTB4 analogs were tested for neutrophil chemoattractant activity using the multiwell cap assay (Evans et al. (1986) Biosc. Rep. 6, 1041). The assay uses disposable equipment and measures chemotaxis by the number of cells able to migrate across the full thickness of cellulose nitrate filters. Under standard conditions (90 min incubation at 37 degrees C in buffer containing 2% bovine albumin), LTB4 and 6-cis-LTB1 had EC50 values of 3.5 and 15,000 nM, respectively. 20-hydroxy-LTB4 was equipotent with LTB4 and exhibited a similar biphasic chemotactic response, however, only one third of the number of cells migrated through the filter. 20-carboxy-LTB4 was inactive up to 1,000 nM. 5-desoxy-((6,7)-cis-cyclopropyl)-LTB2, (6,7)-benzo-LTB2 and 5-desoxy-(8,10)-LTB2 had EC50 values of 11,300, 50,000 and 84,000 nM, respectively. Checkerboard analysis indicated a chemokinetic component of 42% for LTB4 at a concentration causing peak chemotaxis. Reduction of albumin in the buffer to 0.5% increased the apparent potencies of LTB4 and 6-cis-LTB1 five-fold. Since LTB4 is a mediator of inflammation, various anti-inflammatory agents were tested at peak concentrations observed in vivo for in vitro inhibition of LTB4-stimulated chemotaxis in the presence of 0.5% albumin. Under the conditions of the assay, chloroquine diphosphate, dexamethasone, indomethacin, penicillamine, piroxicam and diclofenac sodium were inactive; gold sodium thiomalate was inhibitory (IC50 = 20 microM).

Erythrina excelsa exhibits estrogenic effects in vivo and in vitro and is cytotoxic on breast and colon cancer cell lines.

PubMed

Tchoukouegno Ngueu, Sadrine; Tchoumtchoua, Job; Njamen, Dieudonné; Halabalaki, Maria; Laudenbach-Leschowski, Ute; Diel, Patrick

2016-01-01

Eythrina excelsa Baker (Fabaceae) is a medicinal plant used to treat various ailments including those of the female genital tract. The objective of this study is to investigate the estrogenic and cytotoxic effects of the ethanol extract of the stem bark of E. excelsa. Erythrina excelsa was evaluated in vitro using the yeast estrogen screen (YES). The extract was then tested in a 3-day uterotrophic assay on ovariectomised Wistar rats at doses of 50 and 100 mg/kg BW/d. Cytotoxic effects were assessed on breast (MCF-7) and colon (HT-29) cancer cell lines using the MTT cell viability assay. Additionally, a LC-PDA-ESI (+)-HRMS and HRMS/MS method was developed and applied for the identification of representative secondary metabolites scaffolds in the extract. In the YES, the extract stimulated the transactivation of the estrogen receptor in a dose-dependent manner with an EC50 value of 1.8 μg/mL. In rats, E. excelsa increased uterine wet weight, uterine epithelial height, and the mRNA expression of estrogen-responsive genes in the uterus and liver at 50 whereas at 100 mg/kg BW/d anti-estrogenic effects were observed. In the MTT-assay, a dose-dependent decrease of the viability of both cell lines was observed with EC50 values of 13.6 μg/mL (MCF-7) and 27.7 μg/mL (HT-29). The phytochemical analysis revealed that the extract is rich in isoflavonoids, mainly prenylated and pyran-derivatives thereof. Erythrina excelsa is rich in prenylated and pyran-substituted isoflavonoids, exhibits estrogenic/anti-estrogenic and cytotoxic effects and warrant sufficient interest for deeper investigations.

Solute removal capacity of high cut-off membrane plasma separators.

PubMed

Ohkubo, Atsushi; Kurashima, Naoki; Nakamura, Ayako; Miyamoto, Satoko; Iimori, Soichiro; Rai, Tatemitsu

2013-10-01

In vitro blood filtration was performed by a closed circuit using high cut-off membrane plasma separators, EVACURE EC-2A10 (EC-2A) and EVACURE EC-4A10 (EC-4A). Samples were obtained from sampling sites before the plasma separator, after each plasma separator, and from the ultrafiltrate of each separator. The sieving coefficient (S.C.) of total protein (TP), albumin (Alb), IgG, interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), fibrinogen (Fib), antithrombin III (AT-III), and coagulation factor XIII (FXIII) were calculated. The S.C. of each solute using EC-2A and EC-A4 were as follows; TP: 0.25 and 0.56, Alb: 0.32 and 0.73, IgG: 0.16 and 0.50, IL-6:0.73 and 0.95, IL-8:0.85 and 0.82, TNF-α: 1.07 and 0.99, Fib: 0 and 0, FXIII: 0.07 and 0.17, respectively. When compared with the conventional type of membrane plasma separators, EVACURE could efficiently remove cytokines while retaining coagulation factors such as fibrinogen. Moreover, EC-2A prevented protein loss, whereas EC-4A could remove approximately 50% of IgG. © 2013 The Authors. Therapeutic Apheresis and Dialysis © 2013 International Society for Apheresis.

Toxicity of binary chemical munition destruction products: methylphosphonic acid, methylphosphinic acid, 2-diisopropylaminoethanol, DF neutralent, and QL neutralent.

PubMed

Watson, Rebecca E; Hafez, Ahmed M; Kremsky, Jonathan N; Bizzigotti, George O

2007-01-01

This paper reports the toxicity and environmental impact of neutralents produced from the hydrolysis of binary chemical agent precursor chemicals DF (methylphosphonic difluoride) and QL (2-[bis(1-methylethyl)amino]ethyl ethyl methylphosphonite). Following a literature review of the neutralent mixtures and constituents, basic toxicity tests were conducted to fill data gaps, including acute oral and dermal median lethal dose assays, the Ames mutagenicity test, and ecotoxicity tests. For methylphosphonic acid (MPA), a major constituent of DF neutralent, the acute oral LD(50) in the Sprague-Dawley rat was measured at 1888 mg/kg, and the Ames test using typical tester strains of Salmonella typhimurium and Escherichia coli was negative. The 48-h LC(50) values for pH-adjusted DF neutralent with Daphnia magna and Cyprinodon variegatus were > 2500 mg/L and 1593 mg/L, respectively. The acute oral LD(50) values in the rat for QL neutralent constituents methylphosphinic acid (MP) and 2-diisopropylaminoethanol (KB) were both determined to be 940 mg/kg, and the Ames test was negative for both. Good Laboratory Practice (GLP)-compliant ecotoxicity tests for MP and KB gave 48-h D. magna EC(50) values of 6.8 mg/L and 83 mg/L, respectively. GLP-compliant 96-h C. variegatus assays on MP and KB gave LC(50) values of 73 and 252 mg/L, respectively, and NOEC values of 22 and 108 mg/L. QL neutralent LD(50) values for acute oral and dermal toxicity tests were both > 5000 mg/kg, and the 48-h LD(50) values for D. magna and C. variegatus were 249 and 2500 mg/L, respectively. Using these data, the overall toxicity of the neutralents was assessed.

Comparison of Versant HBV DNA 3.0 and COBAS AmpliPrep-COBAS TaqMan assays for hepatitis B DNA quantitation: Possible clinical implications.

PubMed

Garbuglia, A R; Angeletti, C; Lauria, F N; Zaccaro, P; Cocca, A M; Pisciotta, M; Solmone, M; Capobianchi, M R

2007-12-01

We compared two commercial assays for HBV DNA quantitation, Versant HBV 3.0, System 340 (bDNA; Bayer Diagnostics) and COBAS AmpliPrep-COBAS TaqMan HBV Test (TaqMan; Roche Diagnostics). Analytical sensitivity, calculated on WHO International Standard, predicted 95% detection rate at 11.4 and 520.2IU/ml for TaqMan and bDNA, respectively. Specificity, established on 50 blood donor samples, was 100% and 84% for TaqMan and bDNA, respectively. When using clinical samples, HBV DNA was detected by TaqMan in 21/55 samples negative to bDNA. Mean values of HBV DNA obtained with bDNA were higher than those obtained with TaqMan (4.09log(10)+/-1.90 versus 3.39log(10)+/-2.41, p<0.001), and 24.4% of samples showed differences in viral load values >0.5log(10), without association with HBV genotype. There was a good correlation for HBV DNA concentrations measured by the two assays (r=0.94; p<0.001) within the overlapping range, and the distribution of results with respect to relevant clinical threshold recently confirmed (20,000 and 2000IU/ml) was similar. Approximately 50% of samples with low HBV DNA, appreciated by TaqMan but not by bDNA, were successfully sequenced in pol region, where drug resistance mutations are located.

Determination of elemental carbon in lake sediments using a thermal-optical transmittance (TOT) method

NASA Astrophysics Data System (ADS)

Khan, A. J.; Swami, Kamal; Ahmed, Tanveer; Bari, A.; Shareef, Akhtar; Husain, Liaquat

2009-12-01

An improved chemical oxidation pretreatment method has been developed for the determination of elemental carbon (EC) [also known as black carbon (BC) or soot] in lake sediments, using a thermal-optical transmittance (TOT) carbon analyzer. The method employs six steps: (1) removal of carbonates by treatment with HCl; (2) removal of silicates by treatment with HF + HCl; (3) removal of any remaining carbonates by treatment with HCl; (4) removal of humic acids by treatment with NaOH; and (5) oxidation of kerogens by K 2Cr 2O 7 + H 2SO 4. A critical step of zinc chloride treatment was added; this apparently changes EC's morphology and enhances retention on quartz fiber filter, resulting in several-fold increased chemical yield. EC was determined using the TOT method with modified combustion timings. Carbon black (acetylene) and four NIST standard reference materials (SRMs) were used for quality control, and to assess the precision of the analysis. The EC recoveries from 18 carbon black samples varied from 90 to 111%, with a mean value of 99 ± 6%. The high EC recoveries confirmed the validity of the method. Char reference materials (i.e. chestnut wood and grass char) were used to determine potential contribution to EC in our measurements. The char references containing about 700 mg total organic carbon (OC) contributed ˜1.5% EC. The measured EC values from four NIST standards were 17.0 ± 0.6, 24.2 ± 3.2, 5.6, and 1.9 ± 0.1 mg g dw-1 for SRM-1648, SRM-1649a, SRM-1941b and SRM-8704, respectively. These values in SRMs were in agreement (<±4%) with the previously reported values. The method was applied to determine the EC in sediment cores from an urban lake and a remote mountain lake in the Northeastern United States. The EC concentrations in two lakes mimic the model EC emissions from the industrial revolution in United States.

Predicted EC50 and EC95 of Remifentanil for Smooth Removal of a Laryngeal Mask Airway Under Propofol Anesthesia

PubMed Central

Yoo, Ji Young; Kwak, Hyun Jeong; Lee, Kyung Cheon; Kim, Go Wun

2015-01-01

Purpose The purpose of this study was to determine the effect-site concentration (Ce) of remifentanil in 50% of patients (EC50) and 95% of patients (EC95) for smooth laryngeal mask airway (LMA) removal in adults under propofol and remifentanil anesthesia. Materials and Methods Twenty-five patients of ASA physical status I-II and ages 18-60 years who were to undergo minor gynecological or orthopedic surgery were assessed in this study. Anesthesia was induced and maintained with propofol and remifentanil target-controlled infusion (TCI). Remifentanil was maintained at a predetermined Ce during the emergence period. The modified Dixon's up-and-down method was used to determine the remifentanil concentration, starting from 1.0 ng/mL (step size of 0.2 ng/mL). Successful removal of the LMA was regarded as absence of coughing/gagging, clenched teeth, gross purposeful movements, breath holding, laryngospasm, or desaturation to SpO2<90%. Results The mean±SD Ce of remifentanil for smooth LMA removal after propofol anesthesia was 0.83±0.16 ng/mL. Using isotonic regression with a bootstrapping approach, the estimated EC50 and EC95 of remifentanil Ce were 0.91 ng/mL [95% confidence interval (CI), 0.77-1.07 ng/mL] and 1.35 ng/mL (95% CI, 1.16-1.38 ng/mL), respectively. Conclusion Our results showed that remifentanil TCI at an established Ce is a reliable technique for achieving safe and smooth emergence without coughing, laryngospasm, or other airway reflexes. PMID:26069139

Interaction between endothelial cells and albumin encapsulated droplets in Poiseuille flow

NASA Astrophysics Data System (ADS)

Seda, Robinson; Fowlkes, J. Brian; Bull, Joseph

2012-11-01

Acoustic droplet vaporization (ADV) of DDFP encapsulated microdroplets has the ability to transform these emulsions into larger gas emboli capable of occluding blood vessels for therapy. An albumin shell is able to stabilize the droplet's superheated core, but can also interact with endothelial cells (EC) at the vessel wall if in close proximity. Radial migration of these microdroplets could bring them close enough to make this interaction possible leading to bioeffects that include cell detachment and death if an ADV event occurs. The purpose of this study is to investigate the hydrodynamic conditions (i.e. shear stresses) that make possible this EC-droplet interaction. A flow chamber coated with a monolayer of EC and connected to a syringe pump is used to flow a DDFP droplet solution at physiological shear stresses (1-50 dyne/cm2) and inspected for droplet attachment. Droplets have been observed to interact and reversibly attach to EC in a static environment, thus it is expected that at low shear stress values interaction and further attachment will be possible. Knowing the flow conditions at which this interaction is likely to occur will aid in preventative measures to avoid significant bioeffects associated with ADV near the vessel wall. This work is supported by NIH grant R01EB006476.

Light-absorption of dust and elemental carbon in snow in the Indian Himalayas and the Finnish Arctic

NASA Astrophysics Data System (ADS)

Svensson, Jonas; Ström, Johan; Kivekäs, Niku; Dkhar, Nathaniel B.; Tayal, Shresth; Sharma, Ved P.; Jutila, Arttu; Backman, John; Virkkula, Aki; Ruppel, Meri; Hyvärinen, Antti; Kontu, Anna; Hannula, Henna-Reetta; Leppäranta, Matti; Hooda, Rakesh K.; Korhola, Atte; Asmi, Eija; Lihavainen, Heikki

2018-03-01

Light-absorbing impurities (LAIs) deposited in snow have the potential to substantially affect the snow radiation budget, with subsequent implications for snow melt. To more accurately quantify the snow albedo, the contribution from different LAIs needs to be assessed. Here we estimate the main LAI components, elemental carbon (EC) (as a proxy for black carbon) and mineral dust in snow from the Indian Himalayas and paired the results with snow samples from Arctic Finland. The impurities are collected onto quartz filters and are analyzed thermal-optically for EC, as well as with an additional optical measurement to estimate the light-absorption of dust separately on the filters. Laboratory tests were conducted using substrates containing soot and mineral particles, especially prepared to test the experimental setup. Analyzed ambient snow samples show EC concentrations that are in the same range as presented by previous research, for each respective region. In terms of the mass absorption cross section (MAC) our ambient EC surprisingly had about half of the MAC value compared to our laboratory standard EC (chimney soot), suggesting a less light absorptive EC in the snow, which has consequences for the snow albedo reduction caused by EC. In the Himalayan samples, larger contributions by dust (in the range of 50 % or greater for the light absorption caused by the LAI) highlighted the importance of dust acting as a light absorber in the snow. Moreover, EC concentrations in the Indian samples, acquired from a 120 cm deep snow pit (possibly covering the last five years of snow fall), suggest an increase in both EC and dust deposition. This work emphasizes the complexity in determining the snow albedo, showing that LAI concentrations alone might not be sufficient, but additional transient effects on the light-absorbing properties of the EC need to be considered and studied in the snow. Equally as imperative is the confirmation of the spatial and temporal representativeness of these data by comparing data from several and deeper pits explored at the same time.

Analysis of the Non-LTE Lithium Abundance for a Large Sample of F-, G-, and K-Giants and Supergiants

NASA Astrophysics Data System (ADS)

Lyubimkov, L. S.; Petrov, D. V.

2017-09-01

A five-dimensional interpolation method and corresponding computer program are developed for using published calculations to determine the non-LTE correction ΔNLTE to the lithium abundance logɛ(Li) derived from the Li I 6707.8 Å line. The ΔNLTE value is determined from the following five parameters: the effective temperature Teff, the acceleration of gravity logg, the metallicity index [Fe/H], the microturbulent velocity Vt, and the LTE Li abundance logɛ(Li) . The program is used to calculate values of ΔNLTE and the non-LTE Li abundance for 91 single bright giants from the list of Lebre, et al. By combining these results with data for 55 stars from the previous paper, we obtain the non-LTE values of logɛ(Li) for 146 FGK-giants and supergiants. We confirm that, because of the absence of the Li line in the spectra of most of these stars, it is only possible to estimate for them an upper bound for the Li abundance. A large spread is confirmed in logɛ(Li) for stars with masses M ≤ 6M ⦿ . A comparison of these results with model calculations of stars confirms the unique sensitivity of the lithium abundance to the initial rotation velocity V0. We discuss the giants and supergiants with lithium abundances logɛ(Li) = 1.4 ± 0.3 , which could have a rotational velocity V0=0 km/s and have already undergone deep convective mixing. Li-rich giants with lithium abundances logɛ(Li) ≥ 2 and nearly up to the initial value of logɛ(Li) = 3.2 ± 0.1 are examined. It is shown that the fraction of Li-rich giants with V0 ≈ 0 - 50 km/s is consistent with current evolutionary models. The other stars of this type, as well as all of the "super Li-rich" giants, for which the standard theory is untenable, can be explained by invoking the hypothesis of recent lithium synthesis in the star or an alternative hypothesis according to which a giant planet is engulfed by the star.

Air-sea exchange and gas-particle partitioning of polycyclic aromatic hydrocarbons over the northwestern Pacific Ocean: Role of East Asian continental outflow.

PubMed

Wu, Zilan; Lin, Tian; Li, Zhongxia; Jiang, Yuqing; Li, Yuanyuan; Yao, Xiaohong; Gao, Huiwang; Guo, Zhigang

2017-11-01

We measured 15 parent polycyclic aromatic hydrocarbons (PAHs) in atmosphere and water during a research cruise from the East China Sea (ECS) to the northwestern Pacific Ocean (NWP) in the spring of 2015 to investigate the occurrence, air-sea gas exchange, and gas-particle partitioning of PAHs with a particular focus on the influence of East Asian continental outflow. The gaseous PAH composition and identification of sources were consistent with PAHs from the upwind area, indicating that the gaseous PAHs (three-to five-ring PAHs) were influenced by upwind land pollution. In addition, air-sea exchange fluxes of gaseous PAHs were estimated to be -54.2-107.4 ng m -2 d -1 , and was indicative of variations of land-based PAH inputs. The logarithmic gas-particle partition coefficient (logK p ) of PAHs regressed linearly against the logarithmic subcooled liquid vapor pressure (logP L 0 ), with a slope of -0.25. This was significantly larger than the theoretical value (-1), implying disequilibrium between the gaseous and particulate PAHs over the NWP. The non-equilibrium of PAH gas-particle partitioning was shielded from the volatilization of three-ring gaseous PAHs from seawater and lower soot concentrations in particular when the oceanic air masses prevailed. Modeling PAH absorption into organic matter and adsorption onto soot carbon revealed that the status of PAH gas-particle partitioning deviated more from the modeling K p for oceanic air masses than those for continental air masses, which coincided with higher volatilization of three-ring PAHs and confirmed the influence of air-sea exchange. Meanwhile, significant linear regressions between logK p and logK oa (logK sa ) for PAHs were observed for continental air masses, suggesting the dominant effect of East Asian continental outflow on atmospheric PAHs over the NWP during the sampling campaign. Copyright © 2017 Elsevier Ltd. All rights reserved.

Long term measurement of lake evaporation using a pontoon mounted Eddy Covariance system

NASA Astrophysics Data System (ADS)

McGowan, H. A.; McGloin, R.; McJannet, D.; Burn, S.

2011-12-01

Accurate quantification of evaporation from water storages is essential for design of water management and allocation policy that aims to balance demands for water without compromising the sustainability of future water resources, particularly during periods of prolonged and severe drought. Precise measurement of evaporation from lakes and dams however, presents significant research challenges. These include design and installation of measurement platforms that can withstand a range of wind and wave conditions; accurate determination of the evaporation measurement footprint and the influence of changing water levels. In this paper we present results from a two year long deployment of a pontoon mounted Eddy Covariance (EC) system on a 17.2ha irrigation reservoir in southeast Queensland, Australia. The EC unit included a CSAT-3 sonic anemometer (Campbell Scientific, Utah, United States) and a Li-Cor CS7500 open-path H2O/CO2 infrared gas analyzer (LiCor, Nebraska, United States) at a height of 2.2m, a net radiometer (CNR1, Kipp & Zonen, Netherlands) at a height of 1.2m and a humidity and temperature probe (HMP45C,Vaisala, Finland) at 2.3m. The EC unit was controlled by a Campbell Scientific CR3000 data logger with flux measurements made at 10 Hz and block averaged values logged every 15 minutes. Power to the EC system was from mounted solar panels that charged deep cycle lead-acid batteries while communication was via a cellphone data link. The pontoon was fitted with a weighted central beam and gimbal ring system that allowed self-levelling of the instrumentation and minimized dynamic influences on measurements (McGowan et al 2010; Wiebe et al 2011). EC measurements were corrected for tilt errors using the double rotation method for coordinate rotation described by Wilczak et al. (2001). High and low frequency attenuation of the measured co-spectrum was corrected using Massman's (2000) method for estimating frequency response corrections, while measurements were corrected for density fluctuations using the method of Webb-Pearman-Leuning (Webb et al. 1980). The evaporation measurement footprint over the reservoir was determined using the SCADIS one and a half order turbulence closure footprint model (Sogachev and Lloyd, 2004). Comparison of EC measured evaporation rates show excellent agreement with independent measurement of evaporation by scintillometer under a wide range of conditions (McJannet et al 2011). They confirm that pontoon mounted EC systems offer a robust, highly portable and reliable cost effective approach for accurate quantification of evaporation from reservoirs.

Insights into the CuO nanoparticle ecotoxicity with suitable marine model species.

PubMed

Rotini, A; Gallo, A; Parlapiano, I; Berducci, M T; Boni, R; Tosti, E; Prato, E; Maggi, C; Cicero, A M; Migliore, L; Manfra, L

2018-01-01

Metal oxide nanoparticles, among them copper oxide nanoparticles (CuO NPs), are widely used in different applications (e.g. batteries, gas sensors, superconductors, plastics and metallic coatings), increasing their potential release in the environment. In aquatic matrix, the behavior of CuO NPs may strongly change, depending on their surface charge and some physical-chemical characteristics of the medium (e.g. ionic strength, salinity, pH and natural organic matter content). Ecotoxicity of CuO NPs to aquatic organisms was mainly studied on freshwater species, few tests being performed on marine biota. The aim of this study was to assess the toxicity of CuO NPs on suitable indicator species, belonging to the ecologically relevant level of consumers. The selected bioassays use reference protocols to identify Effect/Lethal Concentrations (E(L)C), by assessing lethal and sub-lethal endpoints. Mortality tests were performed on rotifer (Brachionus plicatilis), shrimp (Artemia franciscana) and copepod (Tigriopus fulvus). While moult release failure and fertilization rate were studied, as sub-lethal endpoints, on T. fulvus and sea urchin (Paracentrotus lividus), respectively. The size distribution and sedimentation rates of CuO NPs, together with the copper dissolution, were also analyzed in the exposure media. The CuO NP ecotoxicity assessment showed a concentration-dependent response for all species, indicating similar mortality for B. plicatilis (48hLC 50 = 16.94 ± 2.68mg/l) and T. fulvus (96hLC 50 = 12.35 ± 0.48mg/l), followed by A. franciscana (48hLC 50 = 64.55 ± 3.54mg/l). Comparable EC 50 values were also obtained for the sub-lethal endpoints in P. lividus (EC 50 = 2.28 ± 0.06mg/l) and T. fulvus (EC 50 = 2.38 ± 0.20mg/l). Copper salts showed higher toxicity than CuO NPs for all species, with common sensitivity trend as follows: P. lividus ≥ T. fulvus (sublethal endpoint) ≥ B. plicatilis >T. fulvus (lethal endpoint) >A. franciscana. CuO NP micrometric aggregates and high sedimentation rates were observed in the exposure media, with different particle size distributions depending on the medium. The copper dissolution was about 0.16% of the initial concentration, comparable to literature values. The integrated ecotoxicological-physicochemical approach was used to better describe CuO NP toxicity and behavior. In particular, the successful application of ecotoxicological reference protocols allowed to produce reliable L(E)C data useful to identify thresholds and assess potential environmental hazard due to NPs. Copyright © 2017 Elsevier Inc. All rights reserved.

Two novel assays for the detection of haemin-binding properties of antimalarials evaluated with compounds isolated from medicinal plants.

PubMed

Steele, J C P; Phelps, R J; Simmonds, M S J; Warhurst, D C; Meyer, D J

2002-07-01

Forty-two compounds isolated from nine plants used within South America for the treatment of malaria were tested for haemin binding using two novel, rapid screening methods. The data obtained were analysed with respect to IC(50) values for in vitro toxicity to Plasmodium falciparum trophozoites. One method, a multiwell assay based on the inhibition of the interaction of haemin with glutathione (GSH), is sensitive in the 10 microM range, takes c. 1 h and is suitable for either a high throughput screen or rapid assay during natural product isolation. Of 19 compounds showing antiplasmodial activity (IC(50) < 40 microM), 16 (84%) showed >40% inhibition of GSH-haemin reaction. The sensitivity and specificity of the assay were 0.85 and 0.82, respectively. The positive predictive value was 0.81 and the negative predictive value 0.86. A more sensitive assay (0.1 microM range) is based on the reversal by haemin-binding compounds of the haemin inhibition of the L-dopachrome-methyl ester tautomerase activity of human macrophage migration inhibitory factor. This assay gives a better idea of the affinity of interaction and uses very small amounts of test compound. The log[RI(50)] of eight of the compounds that tested positive in the above assays together with those of quinine and chloroquine showed a positive correlation with log[antiplasmodial IC(50)] for strain T9-96 (r = 0.824) and strain K1 (r = 0.904). Several of the antimalarial compounds that bind haemin are isoquinolines, a class not shown previously to interact with haemin.

Evaluation of the biodegradability and toxicity of landfill leachates after pretreatment using advanced oxidative processes.

PubMed

da Costa, Fabio Moraes; Daflon, Sarah Dario Alves; Bila, Daniele Maia; da Fonseca, Fabiana Valeria; Campos, Juacyara Carbonelli

2018-06-01

Leachate from urban solid waste landfills is a complex mixture of organic and inorganic substances that cause damage to the environment, due to the high concentration of recalcitrant organic matter and toxicity. The objective of this study was to apply advanced oxidation processes (AOP), namely the dark Fenton and solar photo-Fenton processes, to young and old landfill leachates prior to biological treatment. The leachates were obtained from the Seropedica and Gramacho landfill sites, respectively, located in Rio de Janeiro State, Brazil. For the two Fenton processes, different conditions of pH (1.5, 3.0 and 5.0) and Fe 2+ : H 2 O 2 ratio (1:2, 1:5 and 1:10) were evaluated. Biodegradability was evaluated using the Zahn-Wellens methodology and Aliivibrio fischeri acute toxicity tests were conducted in order to predict the toxicity in the activated sludge. The best conditions for both Fenton processes were pH of 3.0 and Fe 2+ : H 2 O 2 and COD RAW :H 2 O 2 mass ratios of 1:5 and 1:1, respectively. The solar photo-Fenton process was more effective at improving the quality for both leachates, reaching COD, TOC and abs 254 nm reductions of 82%, 85% and 96.3%, respectively, for the Seropedica landfill leachate. In the case of the Gramacho landfill leachate, the corresponding reductions were 78.2, 80.7% and 91.1%, respectively. The biodegradability results for the untreated leachates from the Seropedica and Gramacho sites were 65% and 30% respectively. The biodegradability of both leachates was improved by the Fenton processes, especially the solar photo-Fenton process, which increased the leachate biodegradability to 89% (Seropedica) and 69% (Gramacho). For both leachates, a greater reduction in the acute toxicity was achieved with the solar photo-Fenton compared to the dark-Fenton process. The Seropedica landfill leachate showed high toxicity (EC50 = 33%, 15 min), after the dark Fenton and solar photo Fenton processes, with EC50 values of 81 and 91%, respectively. In the case of Gramacho landfill leachate toxicity, the EC50 value of the raw leachate was 13%, whereas after the dark Fenton and solar photo Fenton processes the corresponding values were 54% and 59%, respectively. These results indicate that the Fenton process (especially solar photo-Fenton), was efficient in terms of increasing the biodegradability and reducing the toxicity of the leachate. This is important in relation to protecting the microbiological community in the activated sludge process. Copyright © 2018 Elsevier Ltd. All rights reserved.

Antioxidant activity, total phenolic and total flavonoid contents of whole plant extracts Torilis leptophylla L

PubMed Central

2012-01-01

Background The aim of this study was to screen various solvent extracts of whole plant of Torilis leptophylla to display potent antioxidant activity in vitro and in vivo, total phenolic and flavonoid contents in order to find possible sources for future novel antioxidants in food and pharmaceutical formulations. Material and methods A detailed study was performed on the antioxidant activity of the methanol extract of whole plant of Torilis leptophylla (TLM) and its derived fractions {n-hexane (TLH), chloroform (TLC) ethyl acetate (TLE) n-butanol (TLB) and residual aqueous fraction (TLA)} by in vitro chemical analyses and carbon tetrachloride (CCl4) induced hepatic injuries (lipid peroxidation and glutathione contents) in male Sprague-Dawley rat. The total yield, total phenolic (TPC) and total flavonoid contents (TFC) of all the fractions were also determined. TLM was also subjected to preliminary phytochemical screening test for various constituents. Results The total phenolic contents (TPC) (121.9±3.1 mg GAE/g extract) of TLM while total flavonoid contents (TFC) of TLE (60.9 ±2.2 mg RTE/g extract) were found significantly higher as compared to other solvent fractions. Phytochemical screening of TLM revealed the presence of alkaloids, anthraquinones, cardiac glycosides, coumarins, flavonoids, saponins, phlobatannins, tannins and terpenoids. The EC50 values based on the DPPH (41.0±1 μg/ml), ABTS (10.0±0.9 μg/ml) and phosphomolybdate (10.7±2 μg/ml) for TLB, hydroxyl radicals (8.0±1 μg/ml) for TLC, superoxide radicals (57.0±0.3 μg/ml) for TLM and hydrogen peroxide radicals (68.0±2 μg/ml) for TLE were generally lower showing potential antioxidant properties. A significant but marginal positive correlation was found between TPC and EC50 values for DPPH, hydroxyl, phosphomolybdate and ABTS, whereas another weak and positive correlation was determined between TFC and EC50 values for superoxide anion and hydroxyl radicals. Results of in vivo experiment revealed that administration of CCl4 caused a significant increase in lipid peroxidation (TBARS) while decrease in GSH contents of liver. In contrast, TLM (200 mg/kg bw) and silymarin (50 mg/kg bw) co-treatment effectively prevented these alterations and maintained the antioxidant status. Conclusion Data from present results revealed that Torilis leptophylla act as an antioxidant agent due to its free radical scavenging and cytoprotective activity. PMID:23153304

Bioactivity-guided mixed synthesis accelerate the serendipity in lead optimization: Discovery of fungicidal homodrimanyl amides.

PubMed

Li, Dangdang; Zhang, Shasha; Song, Zehua; Wang, Guotong; Li, Shengkun

2017-08-18

The bioactivity-guided mixed synthesis was conceived, in which the designed mix-reactions were run in parallel for simultaneous construction of different kinds of analogs. The valuable ones were protruded by biological screening. This tactic will facilitate more rapid incorporation of bioactive candidates into pesticide chemists' repertoire, exemplified by the optimization of less explored homodrimanes as antifungal ingredients. The discovery of D9 as a potent fungicidal agent can be completed in <2 weeks by one student, with EC 50 of 3.33 mg/L and 2.45 mg/L against S. sclerotiorum and B. cinerea, respectively. To confirm the practicability, time-efficiency, and reliability, specific homodrimanes (82 derivatives) were synthesized and elucidated separately and determined for EC 50 values. The SAR correlated well with the intentionally mixed synthesis and the potential was further confirmed by the in vivo bioassay. This methodology will foster more efficient exploration of biologically relevant chemical space of natural products in pesticide discovery, and can also be tailored readily for the lead optimization in medicinal chemistry. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Adverse effects of the SSRI antidepressant sertraline on early life stages of marine invertebrates.

PubMed

Estévez-Calvar, Noelia; Canesi, Laura; Montagna, Michele; Faimali, Marco; Piazza, Veronica; Garaventa, Francesca

2017-07-01

Widespread contamination of coastal environments by emerging compounds includes low concentrations of pharmaceuticals. These pollutants are not currently incorporated in monitoring programs despite their effects on non-target organisms are very little documented. Among the selective serotonin reuptake inhibitor (SSRI) antidepressants, sertraline (SRT) is one of the most prescribed globally. In this work, earlier life stages of Amphibalanus amphitrite, Brachionus plicatilis and Mytilus galloprovincialis were exposed to environmental concentrations of SRT in order to study both sub-lethal and lethal responses in 24/48 h-tests. Low concentrations of SRT altered significantly swimming behavior in A. amphitrite and B. plicatilis giving 48 h-EC 50 (μg/L) of 113.88 and 282.23, respectively whereas higher values were observed for mortality and immobilization. EC 50 embryotoxicity with M. galloprovincialis was 206.80 μg/L. This work add new data about SRT ecotoxicity on marine invertebrates and confirms the applicability of behavioral endpoints to evaluate the environmental impact of antidepressants in marine organisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

Algicidal activity of Salvia miltiorrhiza Bung on Microcystis aeruginosa--towards identification of algicidal substance and determination of inhibition mechanism.

PubMed

Zhang, Chao; Yi, Yang-Lei; Hao, Kai; Liu, Guang-Lu; Wang, Gao-Xue

2013-10-01

The present study was to isolate and identify a potent algicidal compound from extract of Salvia miltiorrhiza and study the potential inhibition mechanism on Microcystis aeruginosa. Column chromatography and bioassay-guided fractionation methods were carried out to yield neo-przewaquinone A, which was identified by spectral analysis. The EC50 of neo-przewaquinone A on M. aeruginosa were 4.68 mg L(-1). In addition, neo-przewaquinone A showed relatively higher security on Chlorella pyrenoidosa and Scenedesmus obliquus, with the EC50 values of 14.78 and 10.37 mg L(-1), respectively. For the potential inhibition mechanisms, neo-przewaquinone A caused M. aeruginosa cells morphologic damage or lysis, increased malondialdehyde content and decreased the soluble protein content, total antioxidant and superoxide dismutase activity, and significantly inhibited three photosynthesis-related genes (psaB, psbD, and rbcL). The results demonstrated the algicidal effect of neo-przewaquinone A on M. aeruginosa and provided the possible inhibition mechanisms. Copyright © 2013 Elsevier Ltd. All rights reserved.

Extended rhodamine photosensitizers for photodynamic therapy of cancer cells.

PubMed

Davies, Kellie S; Linder, Michelle K; Kryman, Mark W; Detty, Michael R

2016-09-01

Extended thio- and selenorhodamines with a linear or angular fused benzo group were prepared. The absorption maxima for these compounds fell between 640 and 700nm. The extended rhodamines were evaluated for their potential as photosensitizers for photodynamic therapy in Colo-26 cells. These compounds were examined for their photophysical properties (absorption, fluorescence, and ability to generate singlet oxygen), for their dark and phototoxicity toward Colo-26 cells, and for their co-localization with mitochondrial-specific agents in Colo-26 and HUT-78 cells. The angular extended rhodamines were effective photosensitizers toward Colo-26 cells with 1.0Jcm(-2) laser light delivered at λmax±2nm with values of EC50 of (2.8±0.4)×10(-7)M for sulfur-containing analogue 6-S and (6.4±0.4)×10(-8)M for selenium-containing analogue 6-Se. The linear extended rhodamines were effective photosensitizers toward Colo-26 cells with 5 and 10Jcm(-2) of broad-band light (EC50's⩽2.4×10(-7)M). Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of scaling and root planing on erythrocyte count, hemoglobin and hematocrit in patients with chronic periodontal disease.

PubMed

Malhotra, Ranjan; Kapoor, Anoop; Grover, Vishakha; Grover, Deepak; Kaur, Aaswin

2012-01-01

Anemia of chronic disease, a cytokine-mediated anemia, is a frequent complication of many chronic inflammatory conditions. The present clinical trial was aimed to evaluate the effect of chronic periodontal disease on erythrocyte count, hemoglobin and hematocrit and the changes produced in these parameters after the provision of periodontal therapy. 40 systemically healthy non-smoker male subjects in the age group of 25 to 50 years suffering with chronic periodontal disease were selected and categorized into 2 groups. Group A was categorized as chronic generalized gingivitis, and Group B was categorized as chronic generalized periodontitis on the basis of clinical findings. The clinical parameters Gingival Index (GI), Probing Pock et Depth (PPD) and Relative Attachment Level (RAL) and laboratory blood investigations viz erythrocyte count (EC), hemoglobin (Hb), hematocrit (HCT) and red cell indices (MCV, MCH, MCHC) were recorded at baseline. Complete oral prophylaxis was performed for all patients. Patients were recalled after 3 weeks and 3 months. The clinical and hematological parameters were re-evaluated to analyze the changes after provision of phase I therapy. The mean values of EC, Hb and HCT were significantly lower in Group B in comparison to Group A, and showed a significantly greater increase at 3 months of observation. However, the values of MCV, MCH and MCHC showed a non significant change during the same observation period in both the groups. Lower values of EC, Hb and HCT in Group B showed that mild anemia is associated with chronic generalized periodontitis, which tends to improve after provision of periodontal therapy. Minimal changes in MCV, MCH and MCHC indicated that the lower values are not due to any vitamin and mineral deficiencies, but secondary to the chronic inflammatory changes associated with chronic periodontal disease.

White Matter Lesions: Prevalence and Clinical Phenotype in Asymptomatic Individuals Aged ≥50 Years.

PubMed

David, Jean-Philippe; Ferrat, Emilie; Parisot, Juliette; Naga, Henri; Lakroun, Samia; Menasria, Feriel; Saddedine, Sofiane; Natella, Pierre-André; Paillaud, Elena; Fromentin, Isabelle; Bastuji-Garin, Sylvie

2016-01-01

To assess the prevalence of early confluent/confluent white matter lesions (ec/cWMLs) in asymptomatic individuals aged ≥50 years and to identify associated clinical phenotypes. Cross-sectional analysis of 141 asymptomatic individuals aged ≥50 years assessed at an outpatient department in France. Brain magnetic resonance imaging was rated using the Fazekas scale. Age-adjusted odds ratios (ORs) and 95% confidence intervals were estimated using logistic models to investigate factors associated with ec/cWMLs; independent risk factors were identified by multivariate analysis. Median age was 63 years; 53.9% were women, 32.6% had hypertension, and 76.6% had ≥1 cardiovascular risk factors. The prevalence of ec/cWMLs was 26.2%. Apart from age, independent risk factors were family history of cardiovascular event (OR = 5.55; 1.13-27.32) and hypertension (2.47; 1.05-5.81). Patients with ec/cWMLs had lower cognitive dual-task walking speed (1.15; 0.98-1.40), MMSE (1.41; 1.06-1.89), and FAB scores (5.21; 1.49-19.84). The Scheltens score was independently associated with the WML severity score. ec/cWMLs are common in asymptomatic community-dwelling individuals aged ≥50 years. They are associated with cardiovascular risk factors, impairments in global and executive cognitive function, and Scheltens score elevation. © 2016 S. Karger AG, Basel.

Biodegradable Polymers Influence the Effect of Atorvastatin on Human Coronary Artery Cells

PubMed Central

Strohbach, Anne; Begunk, Robert; Petersen, Svea; Felix, Stephan B.; Sternberg, Katrin; Busch, Raila

2016-01-01

Drug-eluting stents (DES) have reduced in-stent-restenosis drastically. Yet, the stent surface material directly interacts with cascades of biological processes leading to an activation of cellular defense mechanisms. To prevent adverse clinical implications, to date almost every patient with a coronary artery disease is treated with statins. Besides their clinical benefit, statins exert a number of pleiotropic effects on endothelial cells (ECs). Since maintenance of EC function and reduction of uncontrolled smooth muscle cell (SMC) proliferation represents a challenge for new generation DES, we investigated the effect of atorvastatin (ATOR) on human coronary artery cells grown on biodegradable polymers. Our results show a cell type-dependent effect of ATOR on ECs and SMCs. We observed polymer-dependent changes in IC50 values and an altered ATOR-uptake leading to an attenuation of statin-mediated effects on SMC growth. We conclude that the selected biodegradable polymers negatively influence the anti-proliferative effect of ATOR on SMCs. Hence, the process of developing new polymers for DES coating should involve the characterization of material-related changes in mechanisms of drug actions. PMID:26805825

Distinguishing oil and water layers in a cracked porous medium using pulsed neutron logging data based on Hudson's crack theory

NASA Astrophysics Data System (ADS)

Zhang, Xueang; Yang, Zhichao; Tang, Bin; Wang, Renbo; Wei, Xiong

2018-05-01

During geophysical surveys, water layers may interfere with the detection of oil layers. In order to distinguish between oil and water layers in porous cracked media, research on the properties of the cracks, the oil and water layers, and their relation to pulsed neutron logging characteristics is essential. Using Hudson's crack theory, we simulated oil and water layers in a cracked porous medium with different crack parameters corresponding to the well log responses. We found that, in a cracked medium with medium-angle (40°-50°) cracks, the thermal neutron count peak value is higher and more sensitive than those in low-angle and high-angle crack environments; in addition, the thermal neutron density distribution shows more minimum values than in other cases. Further, the thermal neutron count and the rate of change for the oil layer are greater than those of the water layer, and the time spectrum count peak value for the water layer in middle-high-angle (40°-70°) cracked environments is higher than that of the oil layer. The thermal neutron density distribution sensitivity is higher in the water layer with a range of small crack angles (0°-30°) than in the oil layer with the same range of angles. In comparing the thermal neutron density distribution, thermal neutron count peak, thermal neutron density distribution sensitivity, and time spectrum maximum in the oil and water layers, we find that neutrons in medium-angle (40°-50°) cracked reservoirs are more sensitive to deceleration and absorption than those in water layers; neutrons in approximately horizontal (0°-30°) cracked water layers are more sensitive to deceleration than those in reservoirs. These results can guide future work in the cracked media neutron logging field.

Reduction of nutrients, microbes, and personal care products in domestic wastewater by a benchtop electrocoagulation unit

PubMed Central

Symonds, E. M.; Cook, M. M.; McQuaig, S. M.; Ulrich, R. M.; Schenck, R. O.; Lukasik, J. O.; Van Vleet, E. S.; Breitbart, M.

2015-01-01

To preserve environmental and human health, improved treatment processes are needed to reduce nutrients, microbes, and emerging chemical contaminants from domestic wastewater prior to discharge into the environment. Electrocoagulation (EC) treatment is increasingly used to treat industrial wastewater; however, this technology has not yet been thoroughly assessed for its potential to reduce concentrations of nutrients, a variety of microbial surrogates, and personal care products found in domestic wastewater. This investigation's objective was to determine the efficiency of a benchtop EC unit with aluminum sacrificial electrodes to reduce concentrations of the aforementioned biological and chemical pollutants from raw and tertiary-treated domestic wastewater. EC treatment resulted in significant reductions (p < 0.05, α = 0.05) in phosphate, all microbial surrogates, and several personal care products from raw and tertiary-treated domestic wastewater. When wastewater was augmented with microbial surrogates representing bacterial, viral, and protozoan pathogens to measure the extent of reduction, EC treatment resulted in up to 7-log10 reduction of microbial surrogates. Future pilot and full-scale investigations are needed to optimize EC treatment for the following: reducing nitrogen species, personal care products, and energy consumption; elucidating the mechanisms behind microbial reductions; and performing life cycle analyses to determine the appropriateness of implementation. PMID:25797885

Reduction of nutrients, microbes, and personal care products in domestic wastewater by a benchtop electrocoagulation unit.

PubMed

Symonds, E M; Cook, M M; McQuaig, S M; Ulrich, R M; Schenck, R O; Lukasik, J O; Van Vleet, E S; Breitbart, M

2015-03-23

To preserve environmental and human health, improved treatment processes are needed to reduce nutrients, microbes, and emerging chemical contaminants from domestic wastewater prior to discharge into the environment. Electrocoagulation (EC) treatment is increasingly used to treat industrial wastewater; however, this technology has not yet been thoroughly assessed for its potential to reduce concentrations of nutrients, a variety of microbial surrogates, and personal care products found in domestic wastewater. This investigation's objective was to determine the efficiency of a benchtop EC unit with aluminum sacrificial electrodes to reduce concentrations of the aforementioned biological and chemical pollutants from raw and tertiary-treated domestic wastewater. EC treatment resulted in significant reductions (p < 0.05, α = 0.05) in phosphate, all microbial surrogates, and several personal care products from raw and tertiary-treated domestic wastewater. When wastewater was augmented with microbial surrogates representing bacterial, viral, and protozoan pathogens to measure the extent of reduction, EC treatment resulted in up to 7-log10 reduction of microbial surrogates. Future pilot and full-scale investigations are needed to optimize EC treatment for the following: reducing nitrogen species, personal care products, and energy consumption; elucidating the mechanisms behind microbial reductions; and performing life cycle analyses to determine the appropriateness of implementation.

Reduction of nutrients, microbes, and personal care products in domestic wastewater by a benchtop electrocoagulation unit

NASA Astrophysics Data System (ADS)

Symonds, E. M.; Cook, M. M.; McQuaig, S. M.; Ulrich, R. M.; Schenck, R. O.; Lukasik, J. O.; van Vleet, E. S.; Breitbart, M.

2015-03-01

To preserve environmental and human health, improved treatment processes are needed to reduce nutrients, microbes, and emerging chemical contaminants from domestic wastewater prior to discharge into the environment. Electrocoagulation (EC) treatment is increasingly used to treat industrial wastewater; however, this technology has not yet been thoroughly assessed for its potential to reduce concentrations of nutrients, a variety of microbial surrogates, and personal care products found in domestic wastewater. This investigation's objective was to determine the efficiency of a benchtop EC unit with aluminum sacrificial electrodes to reduce concentrations of the aforementioned biological and chemical pollutants from raw and tertiary-treated domestic wastewater. EC treatment resulted in significant reductions (p < 0.05, α = 0.05) in phosphate, all microbial surrogates, and several personal care products from raw and tertiary-treated domestic wastewater. When wastewater was augmented with microbial surrogates representing bacterial, viral, and protozoan pathogens to measure the extent of reduction, EC treatment resulted in up to 7-log10 reduction of microbial surrogates. Future pilot and full-scale investigations are needed to optimize EC treatment for the following: reducing nitrogen species, personal care products, and energy consumption; elucidating the mechanisms behind microbial reductions; and performing life cycle analyses to determine the appropriateness of implementation.

Human Cytomegalovirus Resistance to Deoxyribosylindole Nucleosides Maps to a Transversion Mutation in the Terminase Subunit-Encoding Gene UL89

PubMed Central

Phan, Quang; Hall, Ellie D.; Breitenbach, Julie M.; Borysko, Katherine Z.; Kamil, Jeremy P.; Townsend, Leroy B.; Drach, John C.

2014-01-01

Human cytomegalovirus (HCMV) infection can cause severe illnesses, including encephalopathy and mental retardation, in immunocompromised and immunologically immature patients. Current pharmacotherapies for treating systemic HCMV infections include ganciclovir, cidofovir, and foscarnet. However, long-term administration of these agents can result in serious adverse effects (myelosuppression and/or nephrotoxicity) and the development of viral strains with reduced susceptibility to drugs. The deoxyribosylindole (indole) nucleosides demonstrate a 20-fold greater activity in vitro (the drug concentration at which 50% of the number of plaques was reduced with the presence of drug compared to the number in the absence of drug [EC50] = 0.34 μM) than ganciclovir (EC50 = 7.4 μM) without any observed increase in cytotoxicity. Based on structural similarity to the benzimidazole nucleosides, we hypothesize that the indole nucleosides target the HCMV terminase, an enzyme responsible for packaging viral DNA into capsids and cleaving the DNA into genome-length units. To test this hypothesis, an indole nucleoside-resistant HCMV strain was isolated, the open reading frames of the genes that encode the viral terminase were sequenced, and a G766C mutation in exon 1 of UL89 was identified; this mutation resulted in an E256Q change in the amino acid sequence of the corresponding protein. An HCMV wild-type strain, engineered with this mutation to confirm resistance, demonstrated an 18-fold decrease in susceptibility to the indole nucleosides (EC50 = 3.1 ± 0.7 μM) compared to that of wild-type virus (EC50 = 0.17 ± 0.04 μM). Interestingly, this mutation did not confer resistance to the benzimidazole nucleosides (EC50 for wild-type HCMV = 0.25 ± 0.04 μM, EC50 for HCMV pUL89 E256Q = 0.23 ± 0.04 μM). We conclude, therefore, that the G766C mutation that results in the E256Q substitution is unique for indole nucleoside resistance and distinct from previously discovered substitutions that confer both indole and benzimidazole nucleoside resistance (D344E and A355T). PMID:25348532

Mixture toxicity of water contaminants-effect analysis using the zebrafish embryo assay (Danio rerio).

PubMed

Schmidt, Susanne; Busch, Wibke; Altenburger, Rolf; Küster, Eberhard

2016-06-01

Three water contaminants were selected to be tested in the zebrafish embryo toxicity test (DarT) in order to investigate the sensitivity of the zebrafish embryo toxicity test with respect to mixture effect detection. The concentration-response curves for the observed effects lethality and hypo-pigmentation were calculated after an exposure of the embryos for 96 h with a fungicide (carbendazim), a plasticizer or propellent precursor (2,4-DNT: 2,4- dinitrotoluene) and an aromatic compound (AαC: 2-amino-9H-pyrido[2,3-b]indol), respectively. Follow-up mixture tests were based on the calculated LC50 or EC50 of the single compounds and combined effects were predicted according to the mixture concepts of concentration addition (CA) and independent action (IA). The order of toxicity for the single substances was carbendazim (LC50 = 1.25 μM) < AαC (LC50 = 8.16 μM) < 2,4-DNT (LC50 = 177.05 μM). For AαC and 2,4 DNT hypo-pigmentation was observed in addition (AαC EC50 = 1.81 μM; 2,4-DNT EC50 = 8.81 μM). Two binary and one ternary mixture were studied on lethality and one on hypo-pigmentation: 2,4-DNT/AαC (LC50 = 119.21 μM, EC50 = 5.37 μM), carbendazim/AαC (LC50 = 4.49 μM) and AαC/Carbendazim/2,4 DNT (LC50 = 108.62 μM). Results showed that the effects were in agreement with the CA model when substances were tested in mixtures. Therefore, in a reasonable worst case scenario substance combination effects in fish embryos were at maximum only prone to overestimation when using CA as the mixture concept. Copyright © 2016 Elsevier Ltd. All rights reserved.

Thermal stability of deep level defects induced by high energy proton irradiation in n-type GaN

NASA Astrophysics Data System (ADS)

Zhang, Z.; Farzana, E.; Sun, W. Y.; Chen, J.; Zhang, E. X.; Fleetwood, D. M.; Schrimpf, R. D.; McSkimming, B.; Kyle, E. C. H.; Speck, J. S.; Arehart, A. R.; Ringel, S. A.

2015-10-01

The impact of annealing of proton irradiation-induced defects in n-type GaN devices has been systematically investigated using deep level transient and optical spectroscopies. Moderate temperature annealing (>200-250 °C) causes significant reduction in the concentration of nearly all irradiation-induced traps. While the decreased concentration of previously identified N and Ga vacancy related levels at EC - 0.13 eV, 0.16 eV, and 2.50 eV generally followed a first-order reaction model with activation energies matching theoretical values for NI and VGa diffusion, irradiation-induced traps at EC - 0.72 eV, 1.25 eV, and 3.28 eV all decrease in concentration in a gradual manner, suggesting a more complex reduction mechanism. Slight increases in concentration are observed for the N-vacancy related levels at EC - 0.20 eV and 0.25 eV, which may be due to the reconfiguration of other N-vacancy related defects. Finally, the observed reduction in concentrations of the states at EC - 1.25 and EC - 3.28 eV as a function of annealing temperature closely tracks the detailed recovery behavior of the background carrier concentration as a function of annealing temperature. As a result, it is suggested that these two levels are likely to be responsible for the underlying carrier compensation effect that causes the observation of carrier removal in proton-irradiated n-GaN.

Chronic toxicity of five metals to the polar marine microalga Cryothecomonas armigera - Application of a new bioassay.

PubMed

Koppel, Darren J; Gissi, Francesca; Adams, Merrin S; King, Catherine K; Jolley, Dianne F

2017-09-01

The paucity of ecotoxicological data for Antarctic organisms is impeding the development of region-specific water quality guidelines. To address this limitation, toxicity testing protocols need to be developed to account for the unique physiology of polar organisms, in particular their slow growth rates. In this study, a toxicity test protocol was developed to investigate the toxicities of five metals to the polar marine microalga Cryothecomonas armigera. The concentrations which reduced population growth rate by 10% (EC10) after 24-d for Cu, Pb, Zn, Cd and Ni were 21.6, 152, 366, 454, and 1220 μg.L -1 , respectively. At the concentrations used in tests, only Cu and Ni were sufficiently toxic to enable the derivation of EC50 values of 63.1 and 1570 μg.L -1 respectively. All metals affected C. armigera's cellular physiology including cellular chlorophyll a fluorescence, cell complexity and size, and lipid concentrations. However, no changes to cellular membrane permeability were observed. The reduction in cellular lipid concentrations was a more sensitive indicator of toxicity for Cd, Ni, and Pb than growth rate inhibition, with EC10 values of 89, 894, and 11 μg.L -1 , respectively, highlighting its potential as a sensitive measure of metal toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Association between differential gene expression and body mass index among endometrial cancers from The Cancer Genome Atlas Project.

PubMed

Roque, Dario R; Makowski, Liza; Chen, Ting-Huei; Rashid, Naim; Hayes, D Neil; Bae-Jump, Victoria

2016-08-01

The Cancer Genome Atlas (TCGA) identified four integrated clusters for endometrial cancer (EC): POLE, MSI, CNL and CNH. We evaluated differences in gene expression profiles of obese and non-obese women with EC and examined the association of body mass index (BMI) within the clusters identified in TCGA. TCGA RNAseq data was used to identify genes related to increasing BMI among ECs. The POLE, MSI and CNL clusters were composed mostly of endometrioid EC. Patient BMI was compared between these three clusters with one-way ANOVA. Association between gene expression and BMI was also assessed while adjusting for confounding effects of potential confounding factors. p-Values testing the association between gene expression and BMI were adjusted for multiple hypothesis testing over the 20,531 genes considered. Mean BMI was statistically different between the ECs in the CNL (35.8) versus POLE (29.8) cluster (p=0.006) and approached significance for the MSI (33.0) versus CNL (35.8) cluster (p=0.05). 181 genes were significantly up- or down-regulated with increasing BMI in endometrioid EC (q-value<0.01), including LPL, IRS-1, IGFBP4, IGFBP7 and the progesterone receptor. DAVID functional annotation analysis revealed significant enrichment in "cell cycle" (adjusted p-value=1.5E-5) and "DNA metabolic processes" (adjusted p-value=1E-3) for the identified genes. Obesity related genes were found to be upregulated with increasing BMI among endometrioid ECs. Patients with POLE tumors have the lowest median BMI when compared to MSI and CNL. Given the heterogeneity among endometrioid EC, consideration should be given to abandoning the Type I and II classification of EC tumors. Copyright © 2016 Elsevier Inc. All rights reserved.