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.

EcXyl43 β-xylosidase: molecular modeling, activity on natural and artificial substrates, and synergism with endoxylanases for lignocellulose deconstruction.

PubMed

Ontañon, Ornella M; Ghio, Silvina; Marrero Díaz de Villegas, Rubén; Piccinni, Florencia E; Talia, Paola M; Cerutti, María L; Campos, Eleonora

2018-06-06

Biomass hydrolysis constitutes a bottleneck for the biotransformation of lignocellulosic residues into bioethanol and high-value products. The efficient deconstruction of polysaccharides to fermentable sugars requires multiple enzymes acting concertedly. GH43 β-xylosidases are among the most interesting enzymes involved in hemicellulose deconstruction into xylose. In this work, the structural and functional properties of β-xylosidase EcXyl43 from Enterobacter sp. were thoroughly characterized. Molecular modeling suggested a 3D structure formed by a conserved N-terminal catalytic domain linked to an ancillary C-terminal domain. Both domains resulted essential for enzymatic activity, and the role of critical residues, from the catalytic and the ancillary modules, was confirmed by mutagenesis. EcXyl43 presented β-xylosidase activity towards natural and artificial substrates while arabinofuranosidase activity was only detected on nitrophenyl α-L-arabinofuranoside (pNPA). It hydrolyzed xylobiose and purified xylooligosaccharides (XOS), up to degree of polymerization 6, with higher activity towards longer XOS. Low levels of activity on commercial xylan were also observed, mainly on the soluble fraction. The addition of EcXyl43 to GH10 and GH11 endoxylanases increased the release of xylose from xylan and pre-treated wheat straw. Additionally, EcXyl43 exhibited high efficiency and thermal stability under its optimal conditions (40 °C, pH 6.5), with a half-life of 58 h. Therefore, this enzyme could be a suitable additive for hemicellulases in long-term hydrolysis reactions. Because of its moderate inhibition by monomeric sugars but its high inhibition by ethanol, EcXyl43 could be particularly more useful in separate hydrolysis and fermentation (SHF) than in simultaneous saccharification and co-fermentation (SSCF) or consolidated bioprocessing (CBP).

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.

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

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.

Electroconvulsive seizures (ECS) do not prevent LPS-induced behavioral alterations and microglial activation.

PubMed

van Buel, E M; Bosker, F J; van Drunen, J; Strijker, J; Douwenga, W; Klein, H C; Eisel, U L M

2015-12-12

Long-term neuroimmune activation is a common finding in major depressive disorder (MDD). Literature suggests a dual effect of electroconvulsive therapy (ECT), a highly effective treatment strategy for MDD, on neuroimmune parameters: while ECT acutely increases inflammatory parameters, such as serum levels of pro-inflammatory cytokines, there is evidence to suggest that repeated ECT sessions eventually result in downregulation of the inflammatory response. We hypothesized that this might be due to ECT-induced attenuation of microglial activity upon inflammatory stimuli in the brain. Adult male C57Bl/6J mice received a series of ten electroconvulsive seizures (ECS) or sham shocks, followed by an intracerebroventricular (i.c.v.) lipopolysaccharide (LPS) or phosphate-buffered saline (PBS) injection. Brains were extracted and immunohistochemically stained for the microglial marker ionized calcium-binding adaptor molecule 1 (Iba1). In addition, a sucrose preference test and an open-field test were performed to quantify behavioral alterations. LPS induced a short-term reduction in sucrose preference, which normalized within 3 days. In addition, LPS reduced the distance walked in the open field and induced alterations in grooming and rearing behavior. ECS did not affect any of these parameters. Phenotypical analysis of microglia demonstrated an LPS-induced increase in microglial activity ranging from 84 to 213 % in different hippocampal regions (CA3 213 %; CA1 84 %; dentate gyrus 131 %; and hilus 123 %). ECS-induced alterations in microglial activity were insignificant, ranging from -2.6 to 14.3 % in PBS-injected mice and from -20.2 to 6.6 % in LPS-injected mice. We were unable to demonstrate an effect of ECS on LPS-induced microglial activity or behavioral alterations.

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.

Bio-active engineered 50 nm silica nanoparticles with bone anabolic activity: therapeutic index, effective concentration, and cytotoxicity profile in vitro

PubMed Central

Ha, Shin-Woo; Sikorski, James A.; Weitzmann, M. Neale; Beck, George R.

2014-01-01

Silica-based nanomaterials are generally considered to be excellent candidates for therapeutic applications particularly related to skeletal metabolism however the current data surrounding the safety of silica based nanomaterials is conflicting. This may be due to differences in size, shape, incorporation of composite materials, surface properties, as well as the presence of contaminants following synthesis. In this study we performed extensive in vitro safety profiling of ~50 nm spherical silica nanoparticles with OH-terminated or Polyethylene Glycol decorated surface, with and without a magnetic core, and synthesized by the Stöber method. Nineteen different cell lines representing all major organ types were used to investigate an in vitro lethal concentration (LC) and results revealed little toxicity in any cell type analyzed. To calculate an in vitro therapeutic index we quantified the effective concentration at 50% response (EC50) for nanoparticle-stimulated mineral deposition activity using primary bone marrow stromal cells (BMSCs). The EC50 for BMSCs was not substantially altered by surface or magnetic core. The calculated Inhibitory concentration 50% (IC50) for pre-osteoclasts was similar to the osteoblastic cells. These results demonstrate the pharmacological potential of certain silica-based nanomaterial formulations for use in treating bone diseases based on a favorable in vitro therapeutic index. PMID:24333519

[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.

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.

Acute toxicity and antispasmodic activities of Achillea wilhelmsii C. Koch.

PubMed

Ali, Niaz; Shah, Syed Wadood Ali; Ahmed, Ghayour; Shah, Ismail; Shoaib, Mohammad; Junaid, Muhammad; Ali, Waqar

2014-03-01

Since Achillea wilhelmsii is used as antispasmodic in traditional medicine, we conducted our current work to investigate its rationale on scientific grounds. Acute toxicity studies of crude methanol extract of Achillea wilhelmsii (Aw. CMeOH) is also performed. Effect of Aw. CMeOH and its fractions were tested on isolated sections of rabbits' jejunum at test concentrations 0.01, 0.03, 1.0, 3.0, 5.0 and 10mg/ml. The test extracts, in similar concentrations, were also tested on KCl-induced contractions. Calcium chloride curves were constructed for those fractions which relaxed KCl induced contractions in the absence and presence of the test samples to investigate its possible mode of action through calcium channels. Aw. CMeOH tested positive for flavonoids, saponins, tannins, glycosides, terpenoids, sterols, phenols, carbohydrates and proteins. LD(50) for acute toxicity studies is 2707±12.6 mg/kg. Mean EC(50) values for Aw. CMeOH on spontaneous and KCl-induced contractions are 3.41±0.18 (2.56-3.8, n=6) and 0.68±0.05 (0.6-0.85, n=6) mg/ml, respectively. Respective EC(50) values for n-hexane fraction on spontaneous and KCl-induced contractions are 3.06±0.08 (2.8-3.3, n=6) and 1.68±0.8 (1.4-1.9, n=6) mg/ml, respectively. Corresponding EC(50) (mg/ml) values for chloroformic, ethylacetate and aqueous fractions of Achillea wilhelmsii on spontaneous rabbits' jejunum preparations are 4.8±0.2 (4.41-5.63, n=6), 5.07±0.15 (4.7-5.58, n=6) and 5.2±0.13 (4.91-5.64, n=4), respectively. Constructing calcium chloride curves, in the presence of 0.1 mg/ml of Aw. CMeOH, mean EC(50) value (log molar [Ca(++)]) is-1.98±0.03 (-1.89-2.05, n=6) vs. control EC(50) (log molar [Ca(++)])-2.41±0.02 (-2.32-2.44, n=6). Mean EC(50) value (log molar [Ca(++)]) for 0.3 mg/ml n-hexane fraction is-1.76±0.05 (-1.70 -1.93, n=6) vs. control EC(50) (log molar [Ca(++)]) value-2.18±0.07 (-2.0-2.46, n=6). While in the presence of chloroformic fraction (3 mg/ml), mean EC(50) (log molar [Ca(++)]) value

The Nebivolol action on vascular tone is dependent on actin cytoskeleton polymerization and Rho-A activity into ECs and SMCs.

PubMed

Kadi, A; de Isla, N; Moby, V; Lacolley, P; Labrude, P; Stoltz, J F; Menu, P

2014-01-01

Nitric oxide is implicated in the target action of Nebivolol, a selective β1 adrenoceptor blocker used in hypertension treatment. As the Nitric Oxide (NO) production and the actin cytoskeleton are linked, the aim of this work was to study the involvement of actin cytoskeleton on mechanism of action of Nebivolol in cultured endothelial cells. We studied the effect of Nebivolol (200 μM) on actin filaments remodeling and its impact on NO production and eNOS activation. Results showed that Nebivolol perturbs actin filaments polymerization, increases NO production and eNOS activity between 30 minutes and 1 h. Stabilization of actin filaments with phalloïdine (50 μM) abolishes Nebivolol effects on eNOS activation and NO production. Furthermore, Rho-kinase activity decreased during the first hour of Nebivolol treatment, then increased after 3 h, while actin filaments repolymerized, eNOS activation and NO production decreased. In SMCs, Nebivolol induced a decrease in the Rho-kinase activity from 1 h until 24 h of incubation. In conclusion, we suggest that Nebivolol induced NO production in Endothelial Cells (ECs) via complementary actions between actin cytoskeleton remodeling inducing eNOS activation and Rho-kinase implication. The effect of Nebivolol on ECs occurs during the first hour, this effect on SMCs seems to be maintained until 24 h, explaining persisted action of Nebivolol observed in vivo.

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.

Bio-active engineered 50 nm silica nanoparticles with bone anabolic activity: therapeutic index, effective concentration, and cytotoxicity profile in vitro.

PubMed

Ha, Shin-Woo; Sikorski, James A; Weitzmann, M Neale; Beck, George R

2014-04-01

Silica-based nanomaterials are generally considered to be excellent candidates for therapeutic applications particularly related to skeletal metabolism however the current data surrounding the safety of silica based nanomaterials is conflicting. This may be due to differences in size, shape, incorporation of composite materials, surface properties, as well as the presence of contaminants following synthesis. In this study we performed extensive in vitro safety profiling of ∼ 50 nm spherical silica nanoparticles with OH-terminated or Polyethylene Glycol decorated surface, with and without a magnetic core, and synthesized by the Stöber method. Nineteen different cell lines representing all major organ types were used to investigate an in vitro lethal concentration (LC) and results revealed little toxicity in any cell type analyzed. To calculate an in vitro therapeutic index we quantified the effective concentration at 50% response (EC50) for nanoparticle-stimulated mineral deposition activity using primary bone marrow stromal cells (BMSCs). The EC50 for BMSCs was not substantially altered by surface or magnetic core. The calculated Inhibitory concentration 50% (IC50) for pre-osteoclasts was similar to the osteoblastic cells. These results demonstrate the pharmacological potential of certain silica-based nanomaterial formulations for use in treating bone diseases based on a favorable in vitro therapeutic index. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

Glutathione peroxidase (EC 1.11.1.9) and superoxide dismutase (EC 1.15.1.1) activities in riboflavin-deficient rats infected with Plasmodium berghei malaria.

PubMed

Adelekan, D A; Thurnham, D I

1998-03-01

Riboflavin deficiency interferes with the growth and multiplication of malaria parasites as well as the host response to malaria. The objective of the present work was to determine the effects of riboflavin deficiency on erythrocyte glutathione peroxidase (EC 1.11.1.9; GPx) and superoxide dismutase (EC 1.15.1.1; SOD) in rats infected with Plasmodium berghei malaria. Riboflavin in its co-enzyme form, FAD, is required by glutathione reductase (EC 1.6.4.1) to regenerate GSH and GSH is an important cellular antioxidant both in its own right and also as a substrate for the enzyme GPx. Weanling rats were deprived of riboflavin for 8 weeks before intraperitoneal injection of 1 x 10(6) P. berghei parasites. Control animals were weight-matched to the respective riboflavin-deficient group. At 10 d post-infection, parasite counts were higher in the weight-matched control group than the riboflavin-deficient group (P = 0.004). GPx activity was higher in erythrocytes of rats parasitized with P. berghei than comparable non-infected rats regardless of riboflavin status (P < 0.05). As mature erythrocytes do not synthesize new protein, the higher GPx activities were probably due to the presence of the parasite protein. In erythrocytes from riboflavin-deficient rats, GPx activity tended to be lower than in those rats fed on diets adequate in riboflavin (weight-matched controls) whether parasitized or not, but the difference was not significant. Neither riboflavin deficiency nor malaria had any effect on erythrocyte SOD activity. It was concluded that riboflavin deficiency has no marked effect on erythrocyte GPx or SOD activity in the rat.

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.

Present status of developing petroleum-substituting energy (EC)

NASA Astrophysics Data System (ADS)

1993-03-01

The EC has had approximately 50% of its total energy demand supplied by imports from the exterior of the Community. Hence, it is getting important to develop oil-substituting renewable energy as well as to curtail the emission of carbon dioxide. In consideration of these situations, the results of investigation on the energy policy of the European Community are described. The policy comprises three courses: European Energy Charter, formation of an open European Community energy market, and environmental conservation. Particularly, concerning the reduction of carbon dioxide emission, the EC Council has decided to introduce carbon dioxide taxation so as to suppress the carbon dioxide emission in the year 2000 to the 1990 level. The arrangement for its introduction, however, encountered with difficulties because of the opposition of various countries other than the European Community and the industrial world of the European Community. Legislation of the investment promotion law for energy saving and the construction of infrastructure footing and an information network are ineffective due to the sluggish fuel price and economic recession. A plurality of EC member countries are advancing a comprehensive activity within the framework of the joint programs of research, development, and demonstration set for the renewable energy policy ensuring energy supply and environmental harmonization.

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.

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.

Cancer cells cause vascular endothelial cell (vEC) retraction via 12(S)HETE secretion; the possible role of cancer cell derived microparticle.

PubMed

Uchide, Keiji; Sakon, Masato; Ariyoshi, Hideo; Nakamori, Syouji; Tokunaga, Masaru; Monden, Morito

2007-02-01

Cancer cell mediated vascular endothelial cell (vEC) retraction plays a pivotal role in cancer metastasis. The aim of this study is to clarify the biochemical character of vEC retraction factor derived from human breast cancer cell line, MCF-7. In order to estimate vEC retracting activity, transwell chamber assay system was employed. We first tested the effects of trypsin digestion as well as lipid extraction of culture medium (CM). Trypsin digestion of CM resulted in approximately 40% loss of vEC retracting activity and lipid extraction of CM by Brigh and Dyer methods recovered approximately 60% of vEC retracting activity, suggesting that approximately 60% of vEC retracting activity in MCF-7 derived CM is due to lipid. Although Nordihydroguaiaretic acid (NDGA), the specific lipoxygenase inhibitor, suppressed vEC retracting activity in CM, Acetyl salicylic acid (ASA), a specific cyclooxygenase inhibitor, did not affect the activity, suggesting that lipid exerting vEC retracting activity in CM belongs to lipoxygenase mediated arachidonate metabolites. Thin layer chromatography clearly demonstrated that Rf value of lipid vEC retracting factor in CM is identical to 12HETE. Authentic 12(S)HETE, but not 12(R)HETE, showed vEC retracting activity. After the ultracentrifugation of CM, most lipid vEC retracting activity was recovered from the pellet fraction, and flow cytometric analysis using specific antibody against 12(S)HETE clearly showed the association of 12(S)HETE with small particle in CM. These findings suggested the principal involvement of 12(S)HETE in cancer cell derived microparticles in cancer cell mediated vEC retraction.

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.

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.

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.

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.

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

Minimizing antibody surface density on liposomes while sustaining cytokine-activated EC targeting.

PubMed

Almeda, Dariela; Wang, Biran; Auguste, Debra T

2015-02-01

Liposomes may be engineered to target inflamed endothelium by mimicking ligand-receptor interactions between leukocytes and cytokine-activated endothelial cells (ECs). The upregulation and assembly of vascular cell adhesion molecule-1 (VCAM1) and E-selectin on the cell membrane upon exposure to cytokines have shown potential for drug delivery vehicles to target sites of chronic endothelial inflammation, such as atherosclerosis and cancer. Herein, we characterized EC surfaces by measuring the E-selectin and VCAM1 surface densities and adhesion forces of aVCAM1 and aE-selectin to ECs. We quantified the antibody density, ratio, and diffusivity of liposomes to achieve significant binding and internalization. At 1 h, the 1:1 ratio of VCAM1:E-selectin antibodies was significantly higher than 1:0 and 0:1. Significant binding and uptake was achieved at aE-selectin densities as low as 400 molecules/μm(2). The highest levels of binding and uptake were achieved when using a 1:1 ratio of VCAM1:E-selectin antibodies at a density of 1000 molecules/μm(2); this density is 85% lower than previous reports. The binding and uptake of functionalized liposomes were reduced to levels comparable to IgG functionalized liposomes upon a 10-fold reduction in liposome membrane diffusivity. We conclude with a liposomal design that discriminates between healthy and inflamed endothelium while reducing antibody surface presentation. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

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.

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

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.

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

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.

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

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).

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

50 CFR 34.7 - Fair market value appraisals.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Fair market value appraisals. 34.7 Section... (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM REFUGE REVENUE SHARING WITH COUNTIES § 34.7 Fair market value... procedures in order to estimate the fair market value of each area as a whole. The evaluation will be...

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.

40 CFR Table 1a to Subpart Ec of... - Emissions Limits for Small, Medium, and Large HMIWI at Affected Facilities as Defined in § 60.50c...

Code of Federal Regulations, 2010 CFR

2010-07-01

... Waste Incinerators for Which Construction is Commenced After June 20, 1996 Pt. 60, Subpt. Ec, Table 1A... Facilities as Defined in § 60.50c(a)(1) and (2) Pollutant Units (7 percent oxygen, dry basis) Emissions... matter Milligrams per dry standard cubic meter (grains per dry standard cubic foot) 69 (0.03) 34 (0.015...

40 CFR Table 1b to Subpart Ec of... - Emissions Limits for Small, Medium, and Large HMIWI at Affected Facilities as Defined in § 60.50c...

Code of Federal Regulations, 2010 CFR

2010-07-01

... Waste Incinerators for Which Construction is Commenced After June 20, 1996 Pt. 60, Subpt. Ec, Table 1B... Facilities as Defined in § 60.50c(a)(3) and (4) Pollutant Units (7 percent oxygen, dry basis) Emissions... matter Milligrams per dry standard cubic meter (grains per dry standard cubic foot) 66 (0.029) 22 (0.0095...

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.

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.

Requirement of a Relatively High Threshold Level of Mg2+ for Cell Growth of a Rhizoplane Bacterium, Sphingomonas yanoikuyae EC-S001

PubMed Central

Hoo, Henny; Hashidoko, Yasuyuki; Islam, Md. Tofazzal; Tahara, Satoshi

2004-01-01

Mg2+ is one of the essential elements for bacterial cell growth. The presence of the magnesium cation (Mg2+) in various concentrations often affects cell growth restoration in plant-associating bacteria. This study attempted to determine whether Mg2+ levels in Sphingomonas yanoikuyae EC-S001 affected cell growth restoration in the host plant and what the threshold level is. S. yanoikuyae EC-S001, isolated from the rhizoplane of spinach seedlings grown from surface-sterilized seeds under aseptic conditions, displayed uniform dispersion and attachment throughout the rhizoplane and phylloplane of the host seedlings. S. yanoikuyae EC-S001 did not grow in potato-dextrose broth medium but grew well in an aqueous extract of spinach leaves. Chemical investigation of the growth factor in the spinach leaf extract led to identification of the active principle as the magnesium cation. A concentration of ca. 0.10 mM Mg2+ or more allowed S. yanoikuyae EC-S001 to grow in potato-dextrose broth medium. Some saprophytic and/or diazotrophic bacteria used in our experiment were found to have diverse threshold levels for their Mg2+ requirements. For example, Burkholderia cepacia EC-K014, originally isolated from the rhizoplane of a Melastoma sp., could grow even in Mg2+-free Hoagland's no. 2 medium with saccharose and glutamine (HSG medium) and requires a trace level of Mg2+ for its growth. In contrast, S. yanoikuyae EC-S001, together with Bacillus subtilis IFO12113, showed the most drastic restoring responses to subsequent addition of 0.98 mM Mg2+ to Mg2+-free HSG medium. Our studies concluded that Mg2+ is more than just the essential trace element needed for cell growth restoration in S. yanoikuyae EC-S001 and that certain nonculturable bacteria may require a higher concentration of Mg2+ or another specific essential element for their growth. PMID:15345402

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.

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.

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.

Towards Coleoptera-specific high-throughput screening systems for compounds with ecdysone activity: development of EcR reporter assays using weevil (Anthonomus grandis)-derived cell lines and in silico analysis of ligand binding to A. grandis EcR ligand-binding pocket.

PubMed

Soin, Thomas; Iga, Masatoshi; Swevers, Luc; Rougé, Pierre; Janssen, Colin R; Smagghe, Guy

2009-08-01

Molting in insects is regulated by ecdysteroids and juvenile hormones. Several synthetic non-steroidal ecdysone agonists are on the market as insecticides. These ecdysone agonists are dibenzoylhydrazine (DBH) analogue compounds that manifest their toxicity via interaction with the ecdysone receptor (EcR). Of the four commercial available ecdysone agonists, three (tebufenozide, methoxyfenozide and chromafenozide) are highly lepidopteran specific, one (halofenozide) is used to control coleopteran and lepidopteran insects in turf and ornamentals. However, compared to the very high binding affinity of these DBH analogues to lepidopteran EcRs, halofenozide has a low binding affinity for coleopteran EcRs. For the discovery of ecdysone agonists that target non-lepidopteran insect groups, efficient screening systems that are based on the activation of the EcR are needed. We report here the development and evaluation of two coleopteran-specific reporter-based screening systems to discover and evaluate ecdysone agonists. The screening systems are based on the cell lines BRL-AG-3A and BRL-AG-3C that are derived from the weevil Anthonomus grandis, which can be efficiently transduced with an EcR reporter cassette for evaluation of induction of reporter activity by ecdysone agonists. We also cloned the almost full length coding sequence of EcR expressed in the cell line BRL-AG-3C and used it to make an initial in silico 3D-model of its ligand-binding pocket docked with ponasterone A and tebufenozide.

Adaptation of Lorke's method to determine and compare ED50 values: the cases of two anticonvulsants drugs.

PubMed

Garrido-Acosta, Osvaldo; Meza-Toledo, Sergio Enrique; Anguiano-Robledo, Liliana; Valencia-Hernández, Ignacio; Chamorro-Cevallos, Germán

2014-01-01

We determined the median effective dose (ED50) values for the anticonvulsants phenobarbital and sodium valproate using a modification of Lorke's method. This modification allowed appropriate statistical analysis and the use of a smaller number of mice per compound tested. The anticonvulsant activities of phenobarbital and sodium valproate were evaluated in male CD1 mice by maximal electroshock (MES) and intraperitoneal administration of pentylenetetrazole (PTZ). The anticonvulsant ED50 values were obtained through modifications of Lorke's method that involved changes in the selection of the three first doses in the initial test and the fourth dose in the second test. Furthermore, a test was added to evaluate the ED50 calculated by the modified Lorke's method, allowing statistical analysis of the data and determination of the confidence limits for ED50. The ED50 for phenobarbital against MES- and PTZ-induced seizures was 16.3mg/kg and 12.7mg/kg, respectively. The sodium valproate values were 261.2mg/kg and 159.7mg/kg, respectively. These results are similar to those found using the traditional methods of finding ED50, suggesting that the modifications made to Lorke's method generate equal results using fewer mice while increasing confidence in the statistical analysis. This adaptation of Lorke's method can be used to determine median letal dose (LD50) or ED50 for compounds with other pharmacological activities. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

Measuring eating competence: psychometric properties and validity of the ecSatter Inventory.

PubMed

Lohse, Barbara; Satter, Ellyn; Horacek, Tanya; Gebreselassie, Tesfayi; Oakland, Mary Jane

2007-01-01

Assess validity of the ecSatter Inventory (ecSI) to measure eating competence (EC). Concurrent administration of ecSI with validated measures of eating behaviors using on-line and paper-pencil formats. The on-line survey was completed by 370 participants; 462 completed the paper version. Participants included 863 adults with 832 usable surveys from respondents (mean age 36.2 +/- 13.4 years) without eating disorders, mostly female, white, educated, overweight, physically active, and food secure. Of those indicating intent to complete the on-line survey, 80.3% did so; 54% of mailed surveys were returned. Eating and food behaviors compared among EC tertiles and between dichotomous EC categories; internal consistency of ecSI. Analysis of variance, independent t tests, chi-square, factor analysis, logistic regression. Significance level was P < .05. Mean ecSI score was 31.1 +/- 7.5. ecSI included 4 subscales with internal reliability and content validity. Construct validity was supported by specific behavioral profiles for ecSI tertiles and ecSI dichotomized categories. Persons unsatisfied with weight were 54% less likely to be EC; unit increase in the food like index was associated with nearly 3 times greater likelihood of being EC. The ecSatter Inventory is a valid measure of EC and can be used for descriptive and outcome measurements.

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.

Status of Europe's contribution to the ITER EC system

NASA Astrophysics Data System (ADS)

Albajar, F.; Aiello, G.; Alberti, S.; Arnold, F.; Avramidis, K.; Bader, M.; Batista, R.; Bertizzolo, R.; Bonicelli, T.; Braunmueller, F.; Brescan, C.; Bruschi, A.; von Burg, B.; Camino, K.; Carannante, G.; Casarin, V.; Castillo, A.; Cauvard, F.; Cavalieri, C.; Cavinato, M.; Chavan, R.; Chelis, J.; Cismondi, F.; Combescure, D.; Darbos, C.; Farina, D.; Fasel, D.; Figini, L.; Gagliardi, M.; Gandini, F.; Gantenbein, G.; Gassmann, T.; Gessner, R.; Goodman, T. P.; Gracia, V.; Grossetti, G.; Heemskerk, C.; Henderson, M.; Hermann, V.; Hogge, J. P.; Illy, S.; Ioannidis, Z.; Jelonnek, J.; Jin, J.; Kasparek, W.; Koning, J.; Krause, A. S.; Landis, J. D.; Latsas, G.; Li, F.; Mazzocchi, F.; Meier, A.; Moro, A.; Nousiainen, R.; Purohit, D.; Nowak, S.; Omori, T.; van Oosterhout, J.; Pacheco, J.; Pagonakis, I.; Platania, P.; Poli, E.; Preis, A. K.; Ronden, D.; Rozier, Y.; Rzesnicki, T.; Saibene, G.; Sanchez, F.; Sartori, F.; Sauter, O.; Scherer, T.; Schlatter, C.; Schreck, S.; Serikov, A.; Siravo, U.; Sozzi, C.; Spaeh, P.; Spichiger, A.; Strauss, D.; Takahashi, K.; Thumm, M.; Tigelis, I.; Vaccaro, A.; Vomvoridis, J.; Tran, M. Q.; Weinhorst, B.

2015-03-01

The electron cyclotron (EC) system of ITER for the initial configuration is designed to provide 20MW of RF power into the plasma during 3600s and a duty cycle of up to 25% for heating and (co and counter) non-inductive current drive, also used to control the MHD plasma instabilities. The EC system is being procured by 5 domestic agencies plus the ITER Organization (IO). F4E has the largest fraction of the EC procurements, which includes 8 high voltage power supplies (HVPS), 6 gyrotrons, the ex-vessel waveguides (includes isolation valves and diamond windows) for all launchers, 4 upper launchers and the main control system. F4E is working with IO to improve the overall design of the EC system by integrating consolidated technological advances, simplifying the interfaces, and doing global engineering analysis and assessments of EC heating and current drive physics and technology capabilities. Examples are the optimization of the HVPS and gyrotron requirements and performance relative to power modulation for MHD control, common qualification programs for diamond window procurements, assessment of the EC grounding system, and the optimization of the launcher steering angles for improved EC access. Here we provide an update on the status of Europe's contribution to the ITER EC system, and a summary of the global activities underway by F4E in collaboration with IO for the optimization of the subsystems.

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.

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

Nitroprusside and ECS-induced retrograde amnesia.

PubMed

Sudha, S; Andrade, C; Anand, A; Guido, S; Venkataraman, B V

2001-03-01

Previous research found that the administration of verapamil and felodipine immediately before electroconvulsive shocks (ECS) attenuated ECS-induced retrograde amnesia. This study examined whether sodium nitroprusside, an antihypertensive drug that does not affect calcium channels, has a similar action. Adult male Sprague-Dawley rats received nitroprusside (0.5 mg/kg ip) or saline 3 minutes before each of three once-daily true or sham ECS. Retention of pre-ECS learning was studied 1 day after ECS using a passive avoidance task. Nitroprusside was associated with increased seizure duration in ECS-treated rats, and with enhanced recall in both true and sham ECS groups. The latter finding suggests that nitroprusside nonspecifically improves cognitive functions, and does not support the hypothesis that ECS-induced cognitive impairment is a result of blood-brain barrier breach. Nitric oxide mechanisms may underlie the benefits purveyed by nitroprusside.

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.

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.

Disulfide-stabilized Helical Hairpin Structure and Activity of a Novel Antifungal Peptide EcAMP1 from Seeds of Barnyard Grass (Echinochloa crus-galli)*

PubMed Central

Nolde, Svetlana B.; Vassilevski, Alexander A.; Rogozhin, Eugene A.; Barinov, Nikolay A.; Balashova, Tamara A.; Samsonova, Olga V.; Baranov, Yuri V.; Feofanov, Alexey V.; Egorov, Tsezi A.; Arseniev, Alexander S.; Grishin, Eugene V.

2011-01-01

This study presents purification, activity characterization, and 1H NMR study of the novel antifungal peptide EcAMP1 from kernels of barnyard grass Echinochloa crus-galli. The peptide adopts a disulfide-stabilized α-helical hairpin structure in aqueous solution and thus represents a novel fold among naturally occurring antimicrobial peptides. Micromolar concentrations of EcAMP1 were shown to inhibit growth of several fungal phytopathogens. Confocal microscopy revealed intensive EcAMP1 binding to the surface of fungal conidia followed by internalization and accumulation in the cytoplasm without disturbance of membrane integrity. Close spatial structure similarity between EcAMP1, the trypsin inhibitor VhTI from seeds of Veronica hederifolia, and some scorpion and cone snail toxins suggests natural elaboration of different functions on a common fold. PMID:21561864

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.

Non-Relative Value Unit-Generating Activities Represent One-Fifth of Academic Neuroradiologist Productivity.

PubMed

Wintermark, M; Zeineh, M; Zaharchuk, G; Srivastava, A; Fischbein, N

2016-07-01

A neuroradiologist's activity includes many tasks beyond interpreting relative value unit-generating imaging studies. Our aim was to test a simple method to record and quantify the non-relative value unit-generating clinical activity represented by consults and clinical conferences, including tumor boards. Four full-time neuroradiologists, working an average of 50% clinical and 50% academic activity, systematically recorded all the non-relative value unit-generating consults and conferences in which they were involved during 3 months by using a simple, Web-based, computer-based application accessible from smartphones, tablets, or computers. The number and type of imaging studies they interpreted during the same period and the associated relative value units were extracted from our billing system. During 3 months, the 4 neuroradiologists working an average of 50% clinical activity interpreted 4241 relative value unit-generating imaging studies, representing 8152 work relative value units. During the same period, they recorded 792 non-relative value unit-generating study reviews as part of consults and conferences (not including reading room consults), representing 19% of the interpreted relative value unit-generating imaging studies. We propose a simple Web-based smartphone app to record and quantify non-relative value unit-generating activities including consults, clinical conferences, and tumor boards. The quantification of non-relative value unit-generating activities is paramount in this time of a paradigm shift from volume to value. It also represents an important tool for determining staffing levels, which cannot be performed on the basis of relative value unit only, considering the importance of time spent by radiologists on non-relative value unit-generating activities. It may also influence payment models from medical centers to radiology departments or practices. © 2016 by American Journal of Neuroradiology.

MoisturEC: a new R program for moisture content estimation from electrical conductivity data

USGS Publications Warehouse

Terry, Neil; Day-Lewis, Frederick D.; Werkema, Dale D.; Lane, John W.

2018-01-01

Noninvasive geophysical estimation of soil moisture has potential to improve understanding of flow in the unsaturated zone for problems involving agricultural management, aquifer recharge, and optimization of landfill design and operations. In principle, several geophysical techniques (e.g., electrical resistivity, electromagnetic induction, and nuclear magnetic resonance) offer insight into soil moisture, but data‐analysis tools are needed to “translate” geophysical results into estimates of soil moisture, consistent with (1) the uncertainty of this translation and (2) direct measurements of moisture. Although geostatistical frameworks exist for this purpose, straightforward and user‐friendly tools are required to fully capitalize on the potential of geophysical information for soil‐moisture estimation. Here, we present MoisturEC, a simple R program with a graphical user interface to convert measurements or images of electrical conductivity (EC) to soil moisture. Input includes EC values, point moisture estimates, and definition of either Archie parameters (based on experimental or literature values) or empirical data of moisture vs. EC. The program produces two‐ and three‐dimensional images of moisture based on available EC and direct measurements of moisture, interpolating between measurement locations using a Tikhonov regularization approach.

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.

New sources and antifungal activity of sesquiterpene lactones.

PubMed

Barrero, A F; Oltra, J E; Alvarez, M; Raslan, D S; Saúde, D A; Akssira, M

2000-02-01

In the search for new sources of sesquiterpene lactones, six Centaurea species have been analyzed. The activity against the fungus Cunninghamella echinulata of (+)-cnicin (1) and (+)-salonitenolide (2), isolated from the Centaurea plants, as well as that of (+)-costunolide (3), (-)-dehydrocostuslactone (4), (-)-lychnopholide (5) and (-)-eremantholide C (6), has been evaluated. Compounds 3 and 4 showed noticeable EC50 values, whilst more polar lactones were inactive. These results suggest that a relatively low polarity is one of the molecular requirements for the antifungal activity of sesquiterpene lactones.

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

Classification of drug molecules considering their IC50 values using mixed-integer linear programming based hyper-boxes method.

PubMed

Armutlu, Pelin; Ozdemir, Muhittin E; Uney-Yuksektepe, Fadime; Kavakli, I Halil; Turkay, Metin

2008-10-03

A priori analysis of the activity of drugs on the target protein by computational approaches can be useful in narrowing down drug candidates for further experimental tests. Currently, there are a large number of computational methods that predict the activity of drugs on proteins. In this study, we approach the activity prediction problem as a classification problem and, we aim to improve the classification accuracy by introducing an algorithm that combines partial least squares regression with mixed-integer programming based hyper-boxes classification method, where drug molecules are classified as low active or high active regarding their binding activity (IC50 values) on target proteins. We also aim to determine the most significant molecular descriptors for the drug molecules. We first apply our approach by analyzing the activities of widely known inhibitor datasets including Acetylcholinesterase (ACHE), Benzodiazepine Receptor (BZR), Dihydrofolate Reductase (DHFR), Cyclooxygenase-2 (COX-2) with known IC50 values. The results at this stage proved that our approach consistently gives better classification accuracies compared to 63 other reported classification methods such as SVM, Naïve Bayes, where we were able to predict the experimentally determined IC50 values with a worst case accuracy of 96%. To further test applicability of this approach we first created dataset for Cytochrome P450 C17 inhibitors and then predicted their activities with 100% accuracy. Our results indicate that this approach can be utilized to predict the inhibitory effects of inhibitors based on their molecular descriptors. This approach will not only enhance drug discovery process, but also save time and resources committed.

Enhancement of CCL15 expression and monocyte adhesion to endothelial cells (ECs) after hypoxia/reoxygenation and induction of ICAM-1 expression by CCL15 via the JAK2/STAT3 pathway in ECs.

PubMed

Park, Keun Hyung; Lee, Tae Hoon; Kim, Chan Woo; Kim, Jiyoung

2013-06-15

CCL15, a member of the CC chemokine family, is a potent chemoattractant for leukocytes and endothelial cells (ECs). Given that chemokines play key roles in vascular inflammation, we investigated the effects of hypoxia/reoxygenation (H/R) on expression of human CCL15 and a role of CCL15 in upregulating ICAM-1 in ECs. We found that exposure of ECs to H/R increased expression of CCL15 and ICAM-1, which resulted in an increase in monocyte adhesivity to the ECs. Further studies revealed that knockdown of CCL15 or CCR1 attenuated expression of ICAM-1 in ECs after H/R, suggesting that expression of ICAM-1 is upregulated by CCL15. Stimulation of ECs with CCL15 significantly increased expression of ICAM-1 predominantly via the CCR1 receptor. We observed that phosphorylation of JAK2 and STAT3 was stimulated by CCL15 treatment of ECs. Results from reporter and chromatin immunoprecipitation assays revealed that CCL15 activates transcription from the IFN-γ activation site promoter and stimulates binding of STAT3 to the ICAM-1 promoter. Our data also showed that CCL15 increased cell adhesion of human monocytes to ECs under static and shear-stress conditions. Pretreatment of these cells with inhibitors for JAK, PI3K, and AKT prevented the CCL15-induced expression of ICAM-1 and monocyte adhesion to ECs, suggesting the involvement of those signaling molecules in ICAM-1 gene activation by CCL15. The results suggest that CCR1 and its ligands may be a potential target for treating inflammatory diseases involving upregulation of cell adhesion molecules.

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.

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.

Potentiated virucidal activity of pomegranate rind extract (PRE) and punicalagin against Herpes simplex virus (HSV) when co-administered with zinc (II) ions, and antiviral activity of PRE against HSV and aciclovir-resistant HSV

PubMed Central

Houston, David M. J.; Bugert, Joachim J.; Denyer, Stephen P.

2017-01-01

Background There is a clinical need for new therapeutic products against Herpes simplex virus (HSV). The pomegranate, fruit of the tree Punica granatum L, has since ancient times been linked to activity against infection. This work probed the activity of pomegranate rind extract (PRE) and co-administered zinc (II) ions. Materials and methods PRE was used in conjunction with zinc (II) salts to challenge HSV-1 and aciclovir-resistant HSV in terms of virucidal plaque assay reduction and antiviral activities in epithelial Vero host cells. Cytotoxicity was determined by the MTS assay using a commercial kit. Results Zinc sulphate, zinc citrate, zinc stearate and zinc gluconate demonstrated similar potentiated virucidal activity with PRE against HSV-1 by up to 4-fold. A generally parabolic relationship was observed when HSV-1 was challenged with PRE and varying concentrations of ZnSO4, with a maximum potentiation factor of 5.5. Punicalagin had 8-fold greater virucidal activity than an equivalent mass of PRE. However, antiviral data showed that punicalagin had significantly lower antiviral activity compared to the activity of PRE (EC50 = 0.56 μg mL-1) a value comparable to aciclovir (EC50 = 0.18 μg mL-1); however, PRE also demonstrated potency against aciclovir-resistant HSV (EC50 = 0.02 μg mL-1), whereas aciclovir showed no activity. Antiviral action of PRE was not influenced by ZnSO4. No cytotoxicity was detected with any test solution. Conclusions The potentiated virucidal activity of PRE by coadministered zinc (II) has potential as a multi-action novel topical therapeutic agent against HSV infections, such as coldsores. PMID:28665969

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.

Linear regression techniques for use in the EC tracer method of secondary organic aerosol estimation

NASA Astrophysics Data System (ADS)

Saylor, Rick D.; Edgerton, Eric S.; Hartsell, Benjamin E.

A variety of linear regression techniques and simple slope estimators are evaluated for use in the elemental carbon (EC) tracer method of secondary organic carbon (OC) estimation. Linear regression techniques based on ordinary least squares are not suitable for situations where measurement uncertainties exist in both regressed variables. In the past, regression based on the method of Deming [1943. Statistical Adjustment of Data. Wiley, London] has been the preferred choice for EC tracer method parameter estimation. In agreement with Chu [2005. Stable estimate of primary OC/EC ratios in the EC tracer method. Atmospheric Environment 39, 1383-1392], we find that in the limited case where primary non-combustion OC (OC non-comb) is assumed to be zero, the ratio of averages (ROA) approach provides a stable and reliable estimate of the primary OC-EC ratio, (OC/EC) pri. In contrast with Chu [2005. Stable estimate of primary OC/EC ratios in the EC tracer method. Atmospheric Environment 39, 1383-1392], however, we find that the optimal use of Deming regression (and the more general York et al. [2004. Unified equations for the slope, intercept, and standard errors of the best straight line. American Journal of Physics 72, 367-375] regression) provides excellent results as well. For the more typical case where OC non-comb is allowed to obtain a non-zero value, we find that regression based on the method of York is the preferred choice for EC tracer method parameter estimation. In the York regression technique, detailed information on uncertainties in the measurement of OC and EC is used to improve the linear best fit to the given data. If only limited information is available on the relative uncertainties of OC and EC, then Deming regression should be used. On the other hand, use of ROA in the estimation of secondary OC, and thus the assumption of a zero OC non-comb value, generally leads to an overestimation of the contribution of secondary OC to total measured OC.

Pre-electroconvulsive shock administration of calcium channel blockers reduces retrograde amnesia induced by ECS.

PubMed

Sushma, M; Sudha, S; Guido, S

2004-11-01

Effect of pre-electroconvulsive shock (ECS) administration of calcium channel blockers (CCBs) like verapamil, diltiazem, nifedipine, nimodipine, flunarizine and cinnarizine on retrograde amnesia induced by ECS was examined using passive avoidance paradigm in rats. The groups (Gr 1-7) of adult, male Wistar rats received true ECS with CCBs (5mg/kg; i.p) or vehicle (10 ml/kg; ip) and other groups (Gr 8-14) received sham ECS with CCBs (5mg/kg; i.p) or vehicle (10 ml/kg; i.p). The anti-amnestic activity of CCBs were evaluated using the passive avoidance paradigm in rats. Results showed that, the baseline latencies for all the groups did not differ significantly. Rats receiving true ECS produced significantly lower latencies. There was increase in the post ECS step through latencies of the rats administered CCBs before ECS. Therefore, pre-ECS administration of calcium channel blockers might reduce retrograde amnesia produced by ECS without altering seizure duration.

Terpenes increase the lipid dynamics in the Leishmania plasma membrane at concentrations similar to their IC50 values.

PubMed

Camargos, Heverton Silva; Moreira, Rodrigo Alves; Mendanha, Sebastião Antonio; Fernandes, Kelly Souza; Dorta, Miriam Leandro; Alonso, Antonio

2014-01-01

Although many terpenes have shown antitumor, antibacterial, antifungal, and antiparasitic activity, the mechanism of action is not well established. Electron paramagnetic resonance (EPR) spectroscopy of the spin-labeled 5-doxyl stearic acid revealed remarkable fluidity increases in the plasma membrane of terpene-treated Leishmania amazonensis promastigotes. For an antiproliferative activity assay using 5×10(6) parasites/mL, the sesquiterpene nerolidol and the monoterpenes (+)-limonene, α-terpineol and 1,8-cineole inhibited the growth of the parasites with IC50 values of 0.008, 0.549, 0.678 and 4.697 mM, respectively. The IC50 values of these terpenes increased as the parasite concentration used in the cytotoxicity assay increased, and this behavior was examined using a theoretical treatment of the experimental data. Cytotoxicity tests with the same parasite concentration as in the EPR experiments revealed a correlation between the IC50 values of the terpenes and the concentrations at which they altered the membrane fluidity. In addition, the terpenes induced small amounts of cell lysis (4-9%) at their respective IC50 values. For assays with high cell concentrations (2×10(9) parasites/mL), the incorporation of terpene into the cell membrane was very fast, and the IC50 values observed for 24 h and 5 min-incubation periods were not significantly different. Taken together, these results suggest that terpene cytotoxicity is associated with the attack on the plasma membrane of the parasite. The in vitro cytotoxicity of nerolidol was similar to that of miltefosine, and nerolidol has high hydrophobicity; thus, nerolidol might be used in drug delivery systems, such as lipid nanoparticles to treat leishmaniasis.

Terpenes Increase the Lipid Dynamics in the Leishmania Plasma Membrane at Concentrations Similar to Their IC50 Values

PubMed Central

Camargos, Heverton Silva; Moreira, Rodrigo Alves; Mendanha, Sebastião Antonio; Fernandes, Kelly Souza; Dorta, Miriam Leandro; Alonso, Antonio

2014-01-01

Although many terpenes have shown antitumor, antibacterial, antifungal, and antiparasitic activity, the mechanism of action is not well established. Electron paramagnetic resonance (EPR) spectroscopy of the spin-labeled 5-doxyl stearic acid revealed remarkable fluidity increases in the plasma membrane of terpene-treated Leishmania amazonensis promastigotes. For an antiproliferative activity assay using 5×106 parasites/mL, the sesquiterpene nerolidol and the monoterpenes (+)-limonene, α-terpineol and 1,8-cineole inhibited the growth of the parasites with IC50 values of 0.008, 0.549, 0.678 and 4.697 mM, respectively. The IC50 values of these terpenes increased as the parasite concentration used in the cytotoxicity assay increased, and this behavior was examined using a theoretical treatment of the experimental data. Cytotoxicity tests with the same parasite concentration as in the EPR experiments revealed a correlation between the IC50 values of the terpenes and the concentrations at which they altered the membrane fluidity. In addition, the terpenes induced small amounts of cell lysis (4–9%) at their respective IC50 values. For assays with high cell concentrations (2×109 parasites/mL), the incorporation of terpene into the cell membrane was very fast, and the IC50 values observed for 24 h and 5 min-incubation periods were not significantly different. Taken together, these results suggest that terpene cytotoxicity is associated with the attack on the plasma membrane of the parasite. The in vitro cytotoxicity of nerolidol was similar to that of miltefosine, and nerolidol has high hydrophobicity; thus, nerolidol might be used in drug delivery systems, such as lipid nanoparticles to treat leishmaniasis. PMID:25101672

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.

MoisturEC: A New R Program for Moisture Content Estimation from Electrical Conductivity Data.

PubMed

Terry, Neil; Day-Lewis, Frederick D; Werkema, Dale; Lane, John W

2018-03-06

Noninvasive geophysical estimation of soil moisture has potential to improve understanding of flow in the unsaturated zone for problems involving agricultural management, aquifer recharge, and optimization of landfill design and operations. In principle, several geophysical techniques (e.g., electrical resistivity, electromagnetic induction, and nuclear magnetic resonance) offer insight into soil moisture, but data-analysis tools are needed to "translate" geophysical results into estimates of soil moisture, consistent with (1) the uncertainty of this translation and (2) direct measurements of moisture. Although geostatistical frameworks exist for this purpose, straightforward and user-friendly tools are required to fully capitalize on the potential of geophysical information for soil-moisture estimation. Here, we present MoisturEC, a simple R program with a graphical user interface to convert measurements or images of electrical conductivity (EC) to soil moisture. Input includes EC values, point moisture estimates, and definition of either Archie parameters (based on experimental or literature values) or empirical data of moisture vs. EC. The program produces two- and three-dimensional images of moisture based on available EC and direct measurements of moisture, interpolating between measurement locations using a Tikhonov regularization approach. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Lopez-Alegria performs EMCS-EC replace activity in Destiny laboratory module

NASA Image and Video Library

2006-12-29

ISS014-E-10647 (29 Dec. 2006) --- Astronaut Michael E. Lopez-Alegria, Expedition 14 commander and NASA space station science officer, performs the European Modular Cultivation System (EMSC) -- Experiment Container (EC) replacement in the Destiny laboratory of the International Space Station.

Lopez-Alegria performs EMCS-EC replace activity in Destiny laboratory module

NASA Image and Video Library

2006-12-29

ISS014-E-10639 (29 Dec. 2006) --- Astronaut Michael E. Lopez-Alegria, Expedition 14 commander and NASA space station science officer, performs the European Modular Cultivation System (EMSC) -- Experiment Container (EC) replacement in the Destiny laboratory of the International Space Station.

Design, synthesis, antiviral activity and three-dimensional quantitative structure-activity relationship study of novel 1,4-pentadien-3-one derivatives containing the 1,3,4-oxadiazole moiety.

PubMed

Gan, Xiuhai; Hu, Deyu; Li, Pei; Wu, Jian; Chen, Xuewen; Xue, Wei; Song, Baoan

2016-03-01

1,4-Pentadien-3-one and 1,3,4-oxadiazole derivatives possess good antiviral activities, and their substructure units are usually used in antiviral agent design. In order to discover novel molecules with high antiviral activities, a series of 1,4-pentadien-3-one derivatives containing the 1,3,4-oxadiazole moiety were designed and synthesised. Bioassays showed that most of the title compounds exhibited good inhibitory activities against tobacco mosaic virus (TMV) in vivo. The compound 8f possessing the best protective activity against TMV had an EC50 value of 135.56 mg L(-1) , which was superior to that of ribavirin (435.99 mg L(-1) ). Comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) techniques were used in three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of protective activities, with values of q(2) and r(2) for the CoMFA and CoMSIA models of 0.751 and 0.775 and 0.936 and 0.925 respectively. Compound 8k with higher protective activity (EC50 = 123.53 mg L(-1) ) according to bioassay was designed and synthesised on the basis of the 3D-QSAR models. Some of the title compounds displayed good antiviral activities. 3D-QSAR models revealed that the appropriate compact electron-withdrawing and hydrophobic group at the benzene ring could enhance antiviral activity. These results could provide important structural insights for the design of highly active 1,4-pentadien-3-one derivatives. © 2015 Society of Chemical Industry.

Epigenetic reprogramming governs EcSOD expression during human mammary epithelial cell differentiation, tumorigenesis and metastasis

PubMed Central

Teoh-Fitzgerald, ML; Fitzgerald, MP; Zhong, W; Askeland, RW; Domann, FE

2013-01-01

Expression of the antioxidant enzyme EcSOD in normal human mammary epithelial cells was not recognized until recently. Although expression of EcSOD was not detectable in non-malignant human mammary epithelial cells (HMEC) cultured in conventional two-dimensional (2D) culture conditions, EcSOD protein expression was observed in normal human breast tissues, suggesting that the 2D-cultured condition induces a repressive status of EcSOD gene expression in HMEC. With the use of laminin-enriched extracellular matrix (lrECM), we were able to detect expression of EcSOD when HMEC formed polarized acinar structures in a 3D-culture condition. Repression of the EcSOD-gene expression was again seen when the HMEC acini were sub-cultured as a monolayer, implying that lrECM-induced acinar morphogenesis is essential in EcSOD-gene activation. We have further shown the involvement of DNA methylation in regulating EcSOD expression in HMEC under these cell culture conditions. EcSOD mRNA expression was strongly induced in the 2D-cultured HMEC after treatment with a DNA methyltransferase inhibitor. In addition, epigenetic analyses showed a decrease in the degree of CpG methylation in the EcSOD promoter in the 3D versus 2D-cultured HMEC. More importantly, >80% of clinical mammary adenocarcinoma samples showed significantly decreased EcSOD mRNA and protein expression levels compared with normal mammary tissues and there is an inverse correlation between the expression levels of EcSOD and the clinical stages of breast cancer. Combined bisulfite restriction analysis analysis of some of the tumors also revealed an association of DNA methylation with the loss of EcSOD expression in vivo. Furthermore, overexpression of EcSOD inhibited breast cancer metastasis in both the experimental lung metastasis model and the syngeneic mouse model. This study suggests that epigenetic silencing of EcSOD may contribute to mammary tumorigenesis and that restoring the extracellular superoxide scavenging

N-ω-chloroacetyl-L-ornithine has in-vitro activity against cancer cell lines and in-vivo activity against ascitic and solid tumors.

PubMed

Vargas-Ramírez, Alba L; Medina-Enríquez, Miriam M; Cordero-Rodríguez, Neira I; Ruiz-Cuello, Tatiana; Aguilar-Faisal, Leopoldo; Trujillo-Ferrara, José G; Alcántara-Farfán, Verónica; Rodríguez-Páez, Lorena

2016-07-01

N-ω-chloroacetyl-L-ornithine (NCAO) is an ornithine decarboxylase (ODC) inhibitor that is known to exert cytotoxic and antiproliferative effects on three neoplastic human cancer cell lines (HeLa, MCF-7, and HepG2). Here, we show that NCAO has antiproliferative activity in 13 cancer cell lines, of diverse tissue origin from human and mice, and in a mouse cancer model in vivo. All cell lines were sensitive to NCAO after 72 h of treatment (the EC50 ranged from 1 to 50.6 µmol/l). The Ca Ski cell line was the most sensitive (EC50=1.18±0.07 µmol/l) and MDA-MB-231 was the least sensitive (EC50=50.6±0.3 µmol/l). This ODC inhibitor showed selectivity for cancer cells, exerting almost no cytotoxic effect on the normal Vero cell line (EC50>1000 µmol/l). NCAO induced apoptosis and inhibited tumor cell migration in vitro. Furthermore, in vivo, this compound (at 50 and 100 mg/kg, daily intraperitoneal injection for 7 days) exerted potent antitumor activity against both solid and ascitic tumors in a mouse model using the myeloma (Ag8) cell line. At these same two doses, the toxicological evaluation showed that NCAO has no obvious systemic toxicity. The current results suggest that the antitumor activity is exerted by apoptosis related not only to a local but also a systemic cytotoxic effect exerted by NCAO on tumor cells. The applications for NCAO as an antitumor agent may be extensive; however, further studies are needed to ascertain the antitumor activity on other types of tumor in vivo and to determine the precise molecular mechanism of its activity.

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.

Structure-activity relationship study of peptidomimetic aldehydes as enterovirus 71 3C protease inhibitors.

PubMed

Zhai, Yangyang; Ma, Yuying; Ma, Fei; Nie, Quandeng; Ren, Xuejiao; Wang, Yaxin; Shang, Luqing; Yin, Zheng

2016-11-29

A series of peptidomimetic aldehydes were designed, synthesized, and evaluated for their biochemical activity against 3C protease (3C pro ) and anti-enterovirus 71 (EV71) activity in vitro. Molecular docking revealed that 5s (IC 50  = 0.22 ± 0.07 μM, EC 50  = 0.18 ± 0.05 μM) could bind well to the active site of EV71 3C pro , which was consistent with the biological data compared to reference 5a (IC 50  = 0.54 ± 0.02 μM, EC 50  = 0.26 ± 0.07 μM). Structure and relationship study led to the discovery of aldehyde 5x (IC 50  = 0.10 ± 0.02 μM, EC 50  = 0.11 ± 0.07 μM), which exhibited the most potent 3C pro inhibitory and antiviral activity. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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.

Water fraction of edible medicinal fern Stenochlaena palustris is a potent α-glucosidase inhibitor with concurrent antioxidant activity.

PubMed

Chai, Tsun-Thai; Kwek, Meng-Tee; Ong, Hean-Chooi; Wong, Fai-Chu

2015-11-01

This study aimed to isolate a potent antiglucosidase and antioxidant fraction from Stenochlaena palustris. Extraction was performed with hexane, chloroform, ethyl acetate, methanol, and water. Antiglucosidase, 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging and ferric reducing antioxidant power (FRAP) assays found methanol extract (ME) to be the most active. Water fraction (WF) of ME was a stronger α-glucosidase inhibitor (EC50 2.9 μg/mL) than quercetin, with weak antiamylase activity. WF was a competitive α-glucosidase inhibitor. DPPH scavenging activity of WF (EC50 7.7 μg/mL) was weaker than quercetin. WF (EC50 364 μg/mL) was a stronger hydrogen peroxide scavenger than gallic acid (EC50 838 μg/mL) and was equally strong as quercetin in scavenging superoxide. WF possessed moderate copper chelating activity. WF was enriched in total phenolics (TP) and hydroxycinnamic acids (THC). TP correlated with antioxidant activity (R(2) > 0.76). Only THC correlated with antiglucosidase activity (R(2) = 0.86). Overall, WF demonstrated concurrent, potent antiglucosidase and antioxidant activities. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antileishmanial and immunomodulatory activity of Xylopia discreta.

PubMed

López, R; Cuca, L E; Delgado, G

2009-10-01

This study aimed at determining the in vitro antileishmanial activity of the essential oil and eight extracts obtained from Xylopia discreta. J774 and U937 macrophages were exposed to the different substances to establish the median lethal concentration (LC(50)). The median effective concentration (EC(50)) was obtained by determining the reduction of Leishmania panamensis-infected cells. A selectivity index (SI) (LC(50)/EC(50)) >or= 20 defined a specific activity for one Xylopia discreta leaf extracts and for the essential oil, being these the two that showed the highest activity (SI = 64.8 and 110, respectively in J774 cells). To assess the substances' immunomodulatory activity, pro- and anti-inflammatory soluble mediators produced after treating infected macrophages were quantified by flow cytometry. The leaf methanol extract and the essential oil induced a differential production of monocyte chemoattractant protein-1, a chemokine associated with a Leishmania-resistant phenotype (Th1).

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

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.

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.

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

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

β -decay Q values among the A = 50 Ti-V-Cr isobaric triplet and atomic masses of Ti 46 , 47 , 49 , 50 , V 50 , 51 , and Cr 50 , 52 – 54

DOE PAGES

Kandegedara, R. M. E. B.; Bollen, G.; Eibach, M.; ...

2017-10-20

This manuscript describes a measurement of the Q value for the highly forbidden beta-decays of 50V and the double electron capture decay of 50Cr. The Q value corresponds to the total energy released during the decay and is equivalent to the mass difference between parent and daughter atoms. This mass difference was measured using high precision Penning trap mass spectrometry with the Low Energy Beam and Ion Trap facility at the National Superconducting Cyclotron Laboratory. The Q value enters into theoretical calculations of the half-life and beta-decay spectrum for the decay, so improves these calculations. In addition the Q valuemore » corresponds to the end point energy of the beta-decay spectrum, which has been precisely measured for several highly-forbidden decays using modern low background detector techniques. Hence, our Q value measurements provide a test of systematics for these detectors. In addition, we have measured the absolute atomic masses of 46,47,49,50Ti, 50,51V, and 50,52-52Cr, providing improvements in precision by factors of up to 3. These atomic masses help to strengthen global evaluations of all atomic mass data, such as the Atomic Mass Evaluation.« less

β -decay Q values among the A = 50 Ti-V-Cr isobaric triplet and atomic masses of Ti 46 , 47 , 49 , 50 , V 50 , 51 , and Cr 50 , 52 – 54

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

Kandegedara, R. M. E. B.; Bollen, G.; Eibach, M.

This manuscript describes a measurement of the Q value for the highly forbidden beta-decays of 50V and the double electron capture decay of 50Cr. The Q value corresponds to the total energy released during the decay and is equivalent to the mass difference between parent and daughter atoms. This mass difference was measured using high precision Penning trap mass spectrometry with the Low Energy Beam and Ion Trap facility at the National Superconducting Cyclotron Laboratory. The Q value enters into theoretical calculations of the half-life and beta-decay spectrum for the decay, so improves these calculations. In addition the Q valuemore » corresponds to the end point energy of the beta-decay spectrum, which has been precisely measured for several highly-forbidden decays using modern low background detector techniques. Hence, our Q value measurements provide a test of systematics for these detectors. In addition, we have measured the absolute atomic masses of 46,47,49,50Ti, 50,51V, and 50,52-52Cr, providing improvements in precision by factors of up to 3. These atomic masses help to strengthen global evaluations of all atomic mass data, such as the Atomic Mass Evaluation.« less

Antiandrogenic activity of phthalate mixtures: Validity of concentration addition

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

Christen, Verena; Crettaz, Pierre; Oberli-Schrämmli, Aurelia

2012-03-01

Phthalates and bisphenol A have very widespread use leading to significant exposure of humans. They are suspected to interfere with the endocrine system, including the androgen, estrogen and the thyroid hormone system. Here we analyzed the antiandrogenic activity of six binary, and one ternary mixture of phthalates exhibiting complete antiandrogenic dose–response curves, and binary mixtures of phthalates and bisphenol A at equi-effective concentrations of EC{sub 10}, EC{sub 25} and EC{sub 50} in MDA-kb2 cells. Mixture activity followed the concentration addition (CA) model with a tendency to synergism at high and antagonism at low concentrations. Isoboles and the toxic unit approachmore » (TUA) confirmed the additive to synergistic activity of the binary mixtures BBP + DBP, DBP + DEP and DEP + BPA at high concentrations. Both methods indicate a tendency to antagonism for the EC{sub 10} mixtures BBP + DBP, BBP + DEP and DBP + DEP, and the EC{sub 25} mixture of DBP + BPA. A ternary mixture revealed synergism at the EC{sub 50}, and weak antagonistic activity at the EC{sub 25} level by the TUA. A mixture of five phthalates representing a human urine composition and reflecting exposure to corresponding parent compounds showed no antiandrogenic activity. Our study demonstrates that CA is an appropriate concept to account for mixture effects of antiandrogenic phthalates and bisphenol A. The interaction indicates a departure from additivity to antagonism at low concentrations, probably due to interaction with the androgen receptor and/or cofactors. This study emphasizes that a risk assessment of phthalates should account for mixture effects by applying the CA concept. -- Highlights: ► Antiandrogenic activity of mixtures of 2 and 3 phthalates are assessed in MDA-kb2 cells. ► Mixture activities followed the concentration addition model. ► A tendency to synergism at high and antagonism at low levels occurred.« less

Phytochemistry, cytotoxicity and antiviral activity of Eleusine indica (sambau)

NASA Astrophysics Data System (ADS)

Iberahim, Rashidah; Yaacob, Wan Ahmad; Ibrahim, Nazlina

2015-09-01

Goose grass also known as Eleusine indica (EI) is a local medicinal plant that displays antioxidant, antimicrobial and anticancer activities. The present study is to determine the phytochemical constituents, cytotoxicity and antiviral activities for both crude extract and fraction obtained from the plant. The crude extract contained more secondary metabolites compared to the hexane fraction as gauged using standard phytochemical tests. Cytotoxicity screening against Vero cells using MTT assay showed that the CC50 values for crude extract and hexane fraction were 2.07 and 5.62 mg/ml respectively. The antiviral activity towards Herpes Simplex Virus type 1 (HSV-1) was determined using plaque reduction assay. The selective indices (SI = CC50 / EC50) for both methanol extract and hexane fraction were 12.2 and 6.2 respectively. These results demonstrate that the extract prepared from E. indica possesses phytochemical compound that was non cytotoxic to the cell with potential antiviral activity.

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.

Evaluation of antioxidant activity of three common potato (Solanum tuberosum) cultivars in Iran

PubMed Central

Hesam, Faride; Balali, Gholam Reza; Tehrani, Reza Taheri

2012-01-01

Objectives: Potato (Solanum tuberosum L.), as a whole food, contains high levels of vitamins and important antioxidants including phenolic acids, carotenoids and flavonoids. The objective of this study was to determine the total phenolic content and antioxidant activities of three common potatoes (Solanum tuberosum) cultivars in Iran i.e., Savalan, Agria and Sante. Materials and Methods: Phenolic compound extraction of samples was done with methanol and total phenolic on the basis of folin-ciocalteu assay was estimated as 16.58 to 36.24 mg GAE/100g dry sample. The antioxidant activities of potato extracts on the basis of inhibition of linoleic acid peroxidation and DPPH assay were compared with a commercially available antioxidant, α -tocopherol. Results: Savalan had the highest phenolic content and the highest DPPH radical scavenging activity with EC50 value of 41.815±mg/ml (DB). Also Savalan had the best inhibitory action against linoleic acid oxidation at 94.10±1.89% at 50 mg/ml sample concentration. Methanolic potato extracts had better antioxidant activity than α-tocopherol. Significant (p<0.01) negative correlation was observed between total phenolic content and the EC50 for DPPH radical scavenging activity(R=-0.877), but there was no correlation between total phenolic content and total antioxidant activity. Conclusion: Metanolic extracts of three potato cultivars are able to inhibit the oxidation process. The correlation between total phenolic content and DPPH radical scavenging activity indicates that phenolic compounds are responsible for antiradical activity. PMID:25050234

DOD Electronic Commerce (EC)/Electronic Data Interchange (EDI) in contracting report

NASA Astrophysics Data System (ADS)

1993-12-01

Use of Electronic Commerce (EC)/Electronic Data Interchange (EDI) to support Department of Defense (DoD) procurement processes has been under consideration for some time. A 1988 Deputy Secretary of Defense memo calls for maximum use of EDI, based on 10 years of DoD EDI investigation and experiments. In 1990, Defense Management Review Decision 941 stated, 'The strategic goal of DoD's current efforts is to provide the department with the capability to initiate, conduct, and maintain its external business related transactions and internal logistics, contracting, and financial activities without requiring the use of hard copy media.' The EC in Contracting PAT membership reflected a broad cross section of Military Services and Defense Agencies working on a full-time basis for 60 days. The diversity of the EC in Contracting PAT ensured that the needs and concerns of all DoD components were addressed during the creation of the report. The resultant plan, therefore, represents a comprehensive approach for implementing EC throughout the DoD.

Londrina Activities of Daily Living Protocol: Reproducibility, Validity, and Reference Values in Physically Independent Adults Age 50 Years and Older.

PubMed

Paes, Thaís; Belo, Letícia Fernandes; da Silva, Diego Rodrigues; Morita, Andrea Akemi; Donária, Leila; Furlanetto, Karina Couto; Sant'Anna, Thaís; Pitta, Fabio; Hernandes, Nidia Aparecida

2017-03-01

It is important to assess activities of daily living (ADL) in older adults due to impairment of independence and quality of life. However, there is no objective and standardized protocol available to assess this outcome. Thus, the aim of this study was to verify the reproducibility and validity of a new protocol for ADL assessment applied in physically independent adults age ≥50 y, the Londrina ADL protocol, and to establish an equation to predict reference values of the Londrina ADL protocol. Ninety-three physically independent adults age ≥50 y had their performance in ADL evaluated by registering the time spent to conclude the protocol. The protocol was performed twice. The 6-min walk test, which assesses functional exercise capacity, was used as a validation criterion. A multiple linear regression model was applied, including anthropometric and demographic variables that correlated with the protocol, to establish an equation to predict the protocol's reference values. In general, the protocol was reproducible (intraclass correlation coefficient 0.91). The average difference between the first and second protocol was 5.3%. The new protocol was valid to assess ADL performance in the studied subjects, presenting a moderate correlation with the 6-min walk test (r = -0.53). The time spent to perform the protocol correlated significantly with age (r = 0.45) but neither with weight (r = -0.17) nor with height (r = -0.17). A model of stepwise multiple regression including sex and age showed that age was the only determinant factor to the Londrina ADL protocol, explaining 21% ( P < .001) of its variability. The derived reference equation was: Londrina ADL protocol pred (s) = 135.618 + (3.102 × age [y]). The Londrina ADL protocol was reproducible and valid in physically independent adults age ≥50 y. A reference equation for the protocol was established including only age as an independent variable (r 2 = 0.21), allowing a better interpretation of the protocol

A spectroscopic survey of EC4, an extended cluster in Andromeda's halo

NASA Astrophysics Data System (ADS)

Collins, M. L. M.; Chapman, S. C.; Irwin, M.; Ibata, R.; Martin, N. F.; Ferguson, A. M. N.; Huxor, A.; Lewis, G. F.; Mackey, A. D.; McConnachie, A. W.; Tanvir, N.

2009-07-01

We present a spectroscopic survey of candidate red giant branch stars in the extended star cluster, EC4, discovered in the halo of M31 from our Canada-France-Hawaii Telescope/MegaCam survey, overlapping the tidal streams, Streams`Cp' and `Cr'. These observations used the DEep Imaging Multi-Object Spectrograph mounted on the Keck II telescope to obtain spectra around the CaII triplet region with ~1.3 Å resolution. Six stars lying on the red giant branch within two core radii of the centre of EC4 are found to have an average vr = -287.9+1.9-2.4kms-1 and σv,corr = 2.7+4.2-2.7kms-1, taking instrumental errors into account. The resulting mass-to-light ratio for EC4 is M/L = 6.7+15-6.7Msolar/Lsolar, a value that is consistent with a globular cluster within the 1σ errors we derive. From the summed spectra of our member stars, we find EC4 to be metal-poor, with [Fe/H] = -1.6 +/- 0.15. We discuss several formation and evolution scenarios which could account for our kinematic and metallicity constraints on EC4, and conclude that EC4 is most comparable with an extended globular cluster. We also compare the kinematics and metallicity of EC4 with Streams `Cp' and`Cr', and find that EC4 bears a striking resemblance to Stream`Cp' in terms of velocity, and that the two structures are identical in terms of both their spectroscopic and photometric metallicities. From this, we conclude that EC4 is likely related to Stream`Cp'. The data presented herein were obtained at the W.M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W.M. Keck Foundation. E-mail: mlmc2@ast.cam.ac.uk

Developmental regulation of ecdysone receptor (EcR) and EcR-controlled gene expression during pharate-adult development of honeybees (Apis mellifera)

PubMed Central

Mello, Tathyana R. P.; Aleixo, Aline C.; Pinheiro, Daniel G.; Nunes, Francis M. F.; Bitondi, Márcia M. G.; Hartfelder, Klaus; Barchuk, Angel R.; Simões, Zilá L. P.

2014-01-01

Major developmental transitions in multicellular organisms are driven by steroid hormones. In insects, these, together with juvenile hormone (JH), control development, metamorphosis, reproduction and aging, and are also suggested to play an important role in caste differentiation of social insects. Here, we aimed to determine how EcR transcription and ecdysteroid titers are related during honeybee postembryonic development and what may actually be the role of EcR in caste development of this social insect. In addition, we expected that knocking-down EcR gene expression would give us information on the participation of the respective protein in regulating downstream targets of EcR. We found that in Apis mellifera females, EcR-A is the predominantly expressed variant in postembryonic development, while EcR-B transcript levels are higher in embryos, indicating an early developmental switch in EcR function. During larval and pupal stages, EcR-B expression levels are very low, while EcR-A transcripts are more variable and abundant in workers compared to queens. Strikingly, these transcript levels are opposite to the ecdysteroid titer profile. 20-hydroxyecdysone (20E) application experiments revealed that low 20E levels induce EcR expression during development, whereas high ecdysteroid titers seem to be repressive. By means of RNAi-mediated knockdown (KD) of both EcR transcript variants we detected the differential expression of 234 poly-A+ transcripts encoding genes such as CYPs, MRJPs and certain hormone response genes (Kr-h1 and ftz-f1). EcR-KD also promoted the differential expression of 70 miRNAs, including highly conserved ones (e.g., miR-133 and miR-375), as well honeybee-specific ones (e.g., miR-3745 and miR-3761). Our results put in evidence a broad spectrum of EcR-controlled gene expression during postembryonic development of honeybees, revealing new facets of EcR biology in this social insect. PMID:25566327

[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.

Modulation of Gardos channel activity by cytokines in sickle erythrocytes.

PubMed

Rivera, Alicia; Jarolim, Petr; Brugnara, Carlo

2002-01-01

It has recently been shown that the Gardos channel activity of mouse erythrocytes can be modified by endothelins, suggesting a functional linkage between endothelin receptors and the Gardos channel. Using (86)Rubidium ((86)Rb) influx, effects were estimated of proinflammatory molecules such as platelet activator factor (PAF), endothelin-1 (ET-1), interleukin-10 (IL-10), and regulated on activation normal T cells expressed and secreted (RANTES) on the Gardos channel activity in human normal and sickle red cells. It was found that PAF (EC(50): 15 +/- 7 nM), RANTES (EC(50), 9 +/- 6 ng/mL [1.2 +/- 0.8 nM]), IL-10 (EC(50), 11 +/- 8 ng/mL [204 +/- 148 nM]), and ET-1 (EC(50), 123 +/- 34 nM) induce a significant increase in Gardos channel activity-between 28% and 84%-over the control. In addition, these agents modify the Gardos channel affinity for internal Ca(++) (K(0.5)) by 2- to 6-fold. Biochemical evidence is provided for the presence of ET receptor subtype B in sickle and normal red cells. Furthermore, it was found that ET-1, PAF, RANTES, and IL-10 induce a significant increase in red cell density (P <.05). These data suggest that activation of the Gardos channel is functionally coupled to receptor motifs such as C-X-C (PAF), C-C (RANTES), and ET receptor subtype B. Thus, cell volume regulation or erythrocyte hydration states might be altered by activation of the Gardos channel by cytokines in vivo. The role of these mediators in promoting sickle cell dehydration in vivo is under investigation.

Measuring ECS Interaction with Biomembranes.

PubMed

Angelucci, Clotilde B; Sabatucci, Annalaura; Dainese, Enrico

2016-01-01

Understanding the correct interaction among the different components of the endocannabinoid system (ECS) is fundamental for a proper assessment of the function of endocannabinoids (eCBs) as signaling molecules. The knowledge of how membrane environment is able to modulate intracellular trafficking of eCBs and their interacting proteins holds a huge potential in unraveling new mechanisms of ECS modulation.Here, fluorescence resonance energy transfer (FRET) technique is applied to measure the binding affinity of ECS proteins to model membranes (i.e., large unilamellar vesicles, LUVs). In particular, we describe in details the paradigmatic example of the interaction of recombinant rat FAAH-ΔTM with LUVs constituted by 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC).

50 CFR 217.50 - Specified activity and specified geographical region.

Code of Federal Regulations, 2014 CFR

2014-10-01

... and Missile Launch Activities From San Nicolas Island, CA § 217.50 Specified activity and specified... those persons it authorizes to engage in target missile launch activities and associated aircraft and..., MSST, Terrier, SM-3, or similar) from Alpha Launch Complex and smaller missiles and targets from...

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.

Late-stage divergent synthesis and antifouling activity of geraniol-butenolide hybrid molecules.

PubMed

Takamura, Hiroyoshi; Ohashi, Takumi; Kikuchi, Takahiro; Endo, Noriyuki; Fukuda, Yuji; Kadota, Isao

2017-07-05

Hybrid molecules consisting of geraniol and butenolide were designed and synthesized by the late-stage divergent strategy. In the synthetic route, ring-closing metathesis was utilized for the construction of a butenolide moiety. A biological evaluation of the eight synthetic hybrid compounds revealed that these molecules exhibit antifouling activity against the cypris larvae of the barnacle Balanus (Amphibalanus) amphitrite with EC 50 values of 0.30-1.31 μg mL -1 . These results show that hybridization of the geraniol and butenolide structural motifs resulted in the enhancement of the antifouling activity.

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

Quantitative evaluation of in vitro effects and interactions of active fractions in a Chinese medicinal formula (Yaotongning Capsule) on rat chondrocytes.

PubMed

Zhang, Li-Guo; Ouyang, Xiao-Wen; Wu, Ting-Ting; Ni, Li-Jun; Shi, Wan-Zhong

2014-09-29

Yaotongning Capsule (YTNC) is a Traditional Chinese Medicinal (TCM) formula that has been demonstrated to be effective for osteoarthritis (OA) treatment in clinical use. Many compounds and 10 component medicinal materials (CMMs for short, i.e., the fundamental elements used in TCM formulas) in YTNC are challenging to study the pharmacological effects and interactions of the CMMs. Besides, it is difficult to know whether the YTNC formula is reasonable, and if YTNC formula could be improved without comparing YTNC with other TCM formulas of treating OA. Based on different combinations of the active fractions from the 10 CMMs of YTNC and eight additional herbs frequently used in the TCM formulas of treating OA, the present study evaluated systematically the in vitro effects of these active fractions and the interactions among the active fractions from YTNC on rat chondrocytes to find possible solutions of the above questions. Based on the formulation of YTNC and the concept of combinatorial chemistry, the active fractions were applied to form the whole YTNC prescription (i.e., the combination of all YTNC active fractions and the extract of YTNC׳s vehicle), five disassembled formulas of YTNC (i.e., the combinations of some active fractions in YTNC) and 21 TCM samples consisted of different kinds of active fractions. The degenerated chondrocytes were induced with interleukin-1β (IL-1β), and then the half-effective concentration (EC50) value of the proliferation activity was analyzed to evaluate the 27 TCM samples. Nine samples were screened for the following evaluation on glycosaminoglycan (GAG) synthesis. Rat articular cartilage was obtained from six Sprague-Dawley rats (seven days of age), and then chondrocytes were isolated through enzymatic digestion with 0.2% Collagenase II. Proliferations of chondrocytes were examined through Cell Counting Kit-8 assay, when the intracellular levels of GAG were detected by 1,9-Dimethylmethylene blue staining. The interactions

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.

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.

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.

Conceptual design of the EU DEMO EC-system: main developments and R&D achievements

NASA Astrophysics Data System (ADS)

Granucci, G.; Aiello, G.; Alberti, S.; Avramidis, K. A.; Braunmüller, F.; Bruschi, A.; Chelis, J.; Franck, J.; Figini, L.; Gantenbein, G.; Garavaglia, S.; Grossetti, G.; Illy, S.; Ioannidis, Z.; Jelonnek, J.; Kalaria, P.; Latsas, G.; Moro, A.; Pagonakis, I. Gr.; Peponis, D.; Poli, E.; Rispoli, N.; Rzesnicki, T.; Scherer, T.; Strauss, D.; Thumm, M.; Tigelis, I.; Tsironis, C.; Wu, C.; Franke, T.; Tran, M. Q.

2017-11-01

For the development of a DEMOnstration Fusion Power Plant the design of auxiliary heating systems is a key activity in order to achieve controlled burning plasma. The present heating mix considers electron cyclotron resonance heating (ECRH), neutral beam injection (NBI) and ion cyclotron resonance heating (ICRH) with a target power to the plasma of about 50 MW for each system. The main tasks assigned to the EC system are plasma breakdown and assisted start-up, heating to L-H transition and plasma current ramp up to burn, MHD stability control and assistance in plasma current ramp down. The consequent requirements are used for the conceptual design of the EC system, from the RF source to the launcher, with an extensive R&D program focused on relevant technologies to be developed. Gyrotron: the R&D and Advanced Developments on EC RF sources are targeting for gyrotrons operating at 240 GHz, considered as optimum EC Current Drive frequency in case of higher magnetic field than for the 2015 EU DEMO1 baseline. Multi-purpose (multi-frequency) and frequency step-tunable gyrotrons are under investigation to increase the flexibility of the system. As main targets an output power of significantly above 1 MW (target: 2 MW) and a total efficiency higher than 60% are set. The principle feasibility at limits of a 236 GHz, conventional-cavity and, alternatively, of a 238 GHz coaxial-cavity gyrotron are under investigation together with the development of a synthetic diamond Brewster-angle window technology. Advanced developments are on-going in the field of multi-stage depressed collector technologies. Transmission line (TL): different TL options are under investigation and a preliminary study of an evacuated quasi-optical multiple-beam TL, considered for a hybrid solution, is presented and discussed in terms of layout, dimensions and theoretical losses. Launcher: remote steering antennas have been considered as a possible launcher solution especially under the constraints to

NPACT: Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database

PubMed Central

Mangal, Manu; Sagar, Parul; Singh, Harinder; Raghava, Gajendra P. S.; Agarwal, Subhash M.

2013-01-01

Plant-derived molecules have been highly valued by biomedical researchers and pharmaceutical companies for developing drugs, as they are thought to be optimized during evolution. Therefore, we have collected and compiled a central resource Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database (NPACT, http://crdd.osdd.net/raghava/npact/) that gathers the information related to experimentally validated plant-derived natural compounds exhibiting anti-cancerous activity (in vitro and in vivo), to complement the other databases. It currently contains 1574 compound entries, and each record provides information on their structure, manually curated published data on in vitro and in vivo experiments along with reference for users referral, inhibitory values (IC50/ED50/EC50/GI50), properties (physical, elemental and topological), cancer types, cell lines, protein targets, commercial suppliers and drug likeness of compounds. NPACT can easily be browsed or queried using various options, and an online similarity tool has also been made available. Further, to facilitate retrieval of existing data, each record is hyperlinked to similar databases like SuperNatural, Herbal Ingredients’ Targets, Comparative Toxicogenomics Database, PubChem and NCI-60 GI50 data. PMID:23203877

Structure-Activity Relationships of Acyclic Selenopurine Nucleosides as Antiviral Agents.

PubMed

Sahu, Pramod K; Umme, Tamima; Yu, Jinha; Kim, Gyudong; Qu, Shuhao; Naik, Siddhi D; Jeong, Lak Shin

2017-07-12

A series of acyclic selenopurine nucleosides 3a - f and 4a - g were synthesized based on the bioisosteric rationale between oxygen and selenium, and then evaluated for antiviral activity. Among the compounds tested, seleno-acyclovir ( 4a ) exhibited the most potent anti-herpes simplex virus (HSV)-1 (EC 50 = 1.47 µM) and HSV-2 (EC 50 = 6.34 µM) activities without cytotoxicity up to 100 µM, while 2,6-diaminopurine derivatives 4e - g exhibited significant anti-human cytomegalovirus (HCMV) activity, which is slightly more potent than the guanine derivative 4d , indicating that they might act as prodrugs of seleno-ganciclovir ( 4d ).

P2Y(2)R activation by nucleotides released from oxLDL-treated endothelial cells (ECs) mediates the interaction between ECs and immune cells through RAGE expression and reactive oxygen species production.

PubMed

Eun, So Young; Park, Sang Won; Lee, Jae Heun; Chang, Ki Churl; Kim, Hye Jung

2014-04-01

Lipoprotein oxidation, inflammation, and immune responses involving the vascular endothelium and immune cells contribute to the pathogenesis of atherosclerosis. In an atherosclerotic animal model, P2Y2 receptor (P2Y2R) upregulation and stimulation were previously shown to induce intimal hyperplasia and increased intimal monocyte infiltration. Thus, we investigated the role of P2Y2R in oxidized low-density lipoprotein (oxLDL)-mediated oxidative stress and the subsequent interaction between endothelial cells (ECs) and immune cells. The treatment of human ECs with oxLDL caused the rapid release of ATP (maximum after 5 min). ECs treated with oxLDL or the P2Y2R agonists ATP/UTP for 1h exhibited significant reactive oxygen species (ROS) production, but this effect was not observed in P2Y2R siRNA-transfected ECs. In addition, oxLDL and ATP/UTP both induced RAGE expression, which was P2Y2R dependent. Oxidized LDL- and ATP/UTP-mediated ROS production was diminished in RAGE siRNA-transfected ECs, suggesting that RAGE is an important mediator in P2Y2R-mediated ROS production. Treatment with oxLDL for 24h induced P2Y2R expression in the human monocyte cell line THP-1 and increased THP-1 cell migration toward ECs. The addition of apyrase, an enzyme that hydrolyzes nucleotides, or diphenyleneiodonium (DPI), a well-known inhibitor of NADPH oxidase, significantly inhibited the increase in cell migration caused by oxLDL. P2Y2R siRNA-transfected THP-1 cells did not migrate in response to oxLDL or ATP/UTP treatment, indicating a critical role for P2Y2R and nucleotide release in oxLDL-induced monocyte migration. Last, oxLDL and ATP/UTP effectively increased ICAM-1 and VCAM-1 expression and the subsequent binding of THP-1 cells to ECs, which was inhibited by pretreatment with DPI or by siRNA against P2Y2R or RAGE, suggesting that P2Y2R is an important mediator in oxLDL-mediated monocyte adhesion to ECs through the regulation of ROS-dependent adhesion molecule expression in ECs. Taken

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

Sorption of biodegradation end products of nonylphenol polyethoxylates onto activated sludge.

PubMed

Hung, Nguyen Viet; Tateda, Masafumi; Ike, Michihiko; Fujita, Masanori; Tsunoi, Shinji; Tanaka, Minoru

2004-01-01

Nonylphenol(NP), nonylphenoxy acetic acid (NP1EC), nonylphenol monoethoxy acetic acid (NP2EC), nonylphenol monoethoxylate (NP1EO) and nonylphenol diethoxylate (NP2EO) are biodegradation end products (BEPs) of nonionic surfactant nonylphenolpolyethoxylates (NPnEO). In this research, sorption of these compounds onto model activated sludge was characterized. Sorption equilibrium experiments showed that NP, NP1EO and NP2EO reached equilibrium in about 12 h, while equilibrium of NP1EC and NP2EC were reached earlier, in about 4 h. In sorption isotherm experiments, obtained equilibrium data at 28 degrees C fitted well to Freundlich sorption model for all investigated compounds. For NP1EC, in addition to Freundlich, equilibrium data also fitted well to Langmuir model. Linear sorption model was also tried, and equilibrium data of all NP, NP1EO, NP2EO and NP2EC except NP1EC fitted well to this model. Calculated Freundlich coefficient (K(F)) and linear sorption coefficient (K(D)) showed that sorption capacity of the investigated compounds were in order NP > NP2EO > NP1EO > NP1EC approximately NP2EC. For NP, NP1EO and NP2EO, high values of calculated K(F) and K(D) indicated an easy uptake of these compounds from aqueous phase onto activated sludge. Whereas, NP1EC and NP2EC with low values of K(F) and K(D) absorbed weakly to activated sludge and tended to preferably remain in aqueous phase.

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.

EC-92: Catalyst for Change

DTIC Science & Technology

1991-04-02

rules of membership and meet the prevailing democratic and judicial standards of the other member states. 16 While only two years ago this possibility...EES/EEA rules affect everyone, not just the EC, then all participants require a role in formulating and accepting the rules . The EC counters that...18 stabilized; members must accept binding rules for the transfer of monetary pol icy to the new bank .34 The most probable shape of the Eurofed, as

Antialgal and antilarval activities of bioactive compounds extracted from the marine dinoflagellate Amphidinium carterae

NASA Astrophysics Data System (ADS)

Kong, Xianyu; Han, Xiurong; Gao, Min; Su, Rongguo; Wang, Ke; Li, Xuzhao; Lu, Wei

2016-12-01

With the global ban on the application of organotin-based marine coatings by the International Maritime Organization, the development of environmentally friendly, low-toxic and nontoxic antifouling compounds for marine industries has become an urgent need. Marine microorganisms have been considered as a potential source of natural antifoulants. In this study, the antifouling potential of marine dinoflagellate Amphidinium carterae, the toxic and red-tide microalgae, was investigated. We performed a series of operations to extract the bioactive substances from Amphidinium carterae and tested their antialgal and antilarval activities. The crude extract of Amphidinium carterae showed significant antialgal activity and the EC50 value against Skeletonema costatum was 55.4 μg mL-1. After purification, the isolated bioactive substances (the organic extract C) exhibited much higher antialgal and antilarval activities with EC50 of 12.9 μg mL-1 against Skeletonema costatum and LC50 of 15.1 μg mL-1 against Amphibalanus amphitrite larvae. Subsequently, IR, Q-TOFMS, and GC-MS were utilized for the structural elucidation of the bioactive compounds, and a series of unsaturated and saturated 16- to 22-carbon fatty acids were detected. The data suggested the bioactive compounds isolated from Amphidinium carterae exhibited a significant inhibiting effect against the diatom Skeletonema costatum and Amphibalanus amphitrite larvae, and could be substitutes for persistent, toxic antifouling compounds.

Biological activities of the polysaccharides produced in submerged culture of two edible Pleurotus ostreatus mushrooms.

PubMed

Vamanu, Emanuel

2012-01-01

Exopolysaccharides (EPS) and internal (intracellular) polysaccharides (IPS) obtained from the Pleurotus ostreatus M2191 and PBS281009 cultivated using the batch system revealed an average of between 0.1-2 (EPS) and 0.07-1.5 g/L/day (IPS). The carbohydrate analysis revealed that the polysaccharides comprised 87-89% EPS and 68-74% IPS. The investigation of antioxidant activity in vitro revealed a good antioxidant potential, particularly for the IPS and EPS isolated from PBS281009, as proved by the EC(50) value for DPPH, ABTS scavenging activity, reducing power, and iron chelating activity.

In vitro and in vivo antiparasitic activity of Physalis angulata L. concentrated ethanolic extract against Trypanosoma cruzi.

PubMed

Meira, Cássio Santana; Guimarães, Elisalva Teixeira; Dos Santos, Jamyle Andrade Ferreira; Moreira, Diogo Rodrigo Magalhães; Nogueira, Renata Campos; Tomassini, Therezinha Coelho Barbosa; Ribeiro, Ivone Maria; de Souza, Claudia Valeria Campos; Ribeiro Dos Santos, Ricardo; Soares, Milena Botelho Pereira

2015-10-15

The current treatment of Chagas disease, endemic in Latin America and emerging in several countries, is limited by the frequent side effects and variable efficacy of benznidazole. Natural products are an important source for the search for new drugs. Considering the great potential of natural products as antiparasitic agents, we investigated the anti-Trypanosoma cruzi activity of a concentrated ethanolic extract of Physalis angulata (EEPA). Cytotoxicity to mammalian cells was determined using mouse peritoneal macrophages. The antiparasitic activity was evaluated against axenic epimastigote and bloodstream trypomastigote forms of T. cruzi, and against amastigote forms using T. cruzi-infected macrophages. Cell death mechanism was determined in trypomastigotes by flow cytometry analysis after annexin V and propidium iodide staining. The efficacy of EEPA was examined in vivo in an acute model of infection by monitoring blood parasitaemia and survival rate 30 days after treatment. The effect against trypomastigotes of EEPA and benznidazole acting in combination was evaluated. EEPA effectively inhibits the epimastigote growth (IC50 2.9 ± 0.1 µM) and reduces bloodstream trypomastigote viability (EC50 1.7 ± 0.5 µM). It causes parasite cell death by necrosis. EEPA impairs parasite infectivity as well as amastigote development in concentrations noncytotoxic to mammalian cells. In mice acutely-infected with T. cruzi, EEPA reduced the blood parasitaemia in 72.7%. When combined with benznidazole, EEPA showed a synergistic anti-T. cruzi activity, displaying CI values of 0.8 ± 0.07 at EC50 and 0.83 ± 0.1 at EC90. EEPA has antiparasitic activity against T. cruzi, causing cell death by necrosis and showing synergistic activity with benznidazole. These findings were reinforced by the observed efficacy of EEPA in reducing parasite load in T. cruzi-mice. Therefore, this represents an important source of antiparasitic natural products. Copyright © 2015 Elsevier GmbH. All rights

Study of activity based costing implementation for palm oil production using value-added and non-value-added activity consideration in PT XYZ palm oil mill

NASA Astrophysics Data System (ADS)

Sembiring, M. T.; Wahyuni, D.; Sinaga, T. S.; Silaban, A.

2018-02-01

Cost allocation at manufacturing industry particularly in Palm Oil Mill still widely practiced based on estimation. It leads to cost distortion. Besides, processing time determined by company is not in accordance with actual processing time in work station. Hence, the purpose of this study is to eliminates non-value-added activities therefore processing time could be shortened and production cost could be reduced. Activity Based Costing Method is used in this research to calculate production cost with Value Added and Non-Value-Added Activities consideration. The result of this study is processing time decreasing for 35.75% at Weighting Bridge Station, 29.77% at Sorting Station, 5.05% at Loading Ramp Station, and 0.79% at Sterilizer Station. Cost of Manufactured for Crude Palm Oil are IDR 5.236,81/kg calculated by Traditional Method, IDR 4.583,37/kg calculated by Activity Based Costing Method before implementation of Activity Improvement and IDR 4.581,71/kg after implementation of Activity Improvement Meanwhile Cost of Manufactured for Palm Kernel are IDR 2.159,50/kg calculated by Traditional Method, IDR 4.584,63/kg calculated by Activity Based Costing Method before implementation of Activity Improvement and IDR 4.582,97/kg after implementation of Activity Improvement.

Antialgal compounds with antialgal activity against the common red tide microalgae from a green algae Ulva pertusa.

PubMed

Sun, Ying-Ying; Zhou, Wen-Jing; Wang, Hui; Guo, Gan-Lin; Su, Zhen-Xia; Pu, Yin-Fang

2018-08-15

Nine antialgal active compounds, (i.e. trehalose (1), twenty-two methyl carbonate (2), (-)-dihydromenisdaurilide (3), 3,7,11,15-tetramethyl-2-hexadecen-1-ol (4), isophytol (5), 8-hexadecenol (6), 17-hydroxyheptadecanoic acid (7), trans-asarone (8) and 2-amino-3-mercaptopropanoic acid (9)) were isolated from Ulva pertusa for the first time by sephadex LH-20 column chromatography, silica gel column chromatography and repeated preparative TLC. Except for compound 4, all compounds represented novel isolated molecules from marine macroalgae. Further, antialgal activities of these compounds against Amphidinium carterae, Heterosigma akashiwo, Karenia mikimitoi, Phaeocystis globosa, Prorocentrum donghaiense and Skeletonema costatum were investigated for the first time. Results showed these nine compounds have selectivity antialgal effects on all test red tide microalgae, and antialgal activities against red tide microalgae obviously enhanced with the increase of concentration of antialgal compounds. Based on this, EC 50-96 h values of these nine compounds for six red tide microalgae were obtained for the first time. By analyzing and comparing EC 50-96 h values, it has been determined that seven compounds (1, 3, 4, 6, 7, 8 and 9) showed the superior application potential than potassium dichromate or gossonorol and other six compounds as a characteristic antialgal agent against Heterosigma akashiwo, Karenia mikimitoi and Prorocentrum donghaiense. Overall this study has suggested that green algae Ulva pertusa is a new source of bioactive compounds with antialgal activity. Copyright © 2018. Published by Elsevier Inc.

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

Sensitivity or artifact? -- IQ Toxicity Test -- effluent values

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

Hayes, K.R.; Novotny, A.N.; Batista, N.

1995-12-31

Several complex effluents were DAPHNIA MAGNA IQ TOXICITY TESTED -- (1.25 hours) and conventionally tested with Daphnia magna (48 hours). In many samples the IQ Technology yielded low EC50 values while the 48 hour exposures yielded no acute toxicity. Possible explanations have been suggested for this occurrence such as: genotoxicity, mutagenicity, substrate interference, and enzyme satiation. To identify the causative agent(s) of this response a Toxicity Identification Evaluation was performed on one of the samples. To define the nature of the response, THE SOS-CHROMOTEST KIT and THE MUTA-CHROMOPLATE KIT were utilized to characterize genotoxicity and mutagenicity respectively. The sample didmore » not test positive for genotoxicity but tested positive for mutagenicity only after activation with S9 enzymes, suggesting the presence of promutagens. Additional work needs to be performed to correlate IQ TOXICITY TEST sensitivity with positive MUTA-CHROMOPLATE response.« less

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

Synthesis and antifungal activity of the derivatives of novel pyrazole carboxamide and isoxazolol pyrazole carboxylate.

PubMed

Sun, Jialong; Zhou, Yuanming

2015-03-09

A series of pyrazole carboxamide and isoxazolol pyrazole carboxylate derivatives were designed and synthesized in this study. The structures of the compounds were elucidated based on spectral data (infrared, proton nuclear magnetic resonance and mass spectroscopy). Then, all of the compounds were bioassayed in vitro against four types of phytopathogenic fungi (Alternaria porri, Marssonina coronaria, Cercospora petroselini and Rhizoctonia solani) using the mycelium growth inhibition method. The results showed that some of the synthesized pyrazole carboxamides displayed notable antifungal activity. The isoxazole pyrazole carboxylate 7ai exhibited significant antifungal activity against R. solani, with an EC50 value of 0.37 μg/mL. Nonetheless, this value was lower than that of the commercial fungicide, carbendazol.

The metabolism of ethanol-derived acetaldehyde by alcohol dehydrogenase (EC 1.1.1.1) and aldehyde dehydrogenase (EC 1.2.1.3) in Drosophila melanogaster larvae.

PubMed Central

Heinstra, P W; Geer, B W; Seykens, D; Langevin, M

1989-01-01

Both aldehyde dehydrogenase (ALDH, EC 1.2.1.3) and the aldehyde dehydrogenase activity of alcohol dehydrogenase (ADH, EC 1.1.1.1) were found to coexist in Drosophila melanogaster larvae. The enzymes, however, showed different inhibition patterns with respect to pyrazole, cyanamide and disulphiram. ALDH-1 and ALDH-2 isoenzymes were detected in larvae by electrophoretic methods. Nonetheless, in tracer studies in vivo, more than 75% of the acetaldehyde converted to acetate by the ADH ethanol-degrading pathway appeared to be also catalysed by the ADH enzyme. The larval fat body probably was the major site of this pathway. Images Fig. 1. Fig. 2. PMID:2499314

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.

In vitro anti-herpes simplex virus-2 activity of Salvia desoleana Atzei & V. Picci essential oil

PubMed Central

Sanna, Cinzia; Cagliero, Cecilia; Ballero, Mauro; Civra, Andrea; Donalisio, Manuela; Bicchi, Carlo; Lembo, David

2017-01-01

Salvia desoleana Atzei & V. Picci is an indigenous species in Sardinia island used in folk medicine to treat menstrual, digestive and central nervous system diseases. Nowadays, it is widely cultivated for the pleasant smell of its essential oil (EO), whose antimicrobial and antifungal activities have already been screened. This study evaluated the in vitro anti-Herpes Simplex Virus-2 (HSV-2) activity of S. desoleana EO, fractions and main components: linalyl acetate, alpha terpinyl acetate, and germacrene D. Phytochemical composition of S. desoleana EO was studied by GC-FID/MS analysis and the active fraction(s) and/or compounds in S. desoleana EO were identified with a bioassay-guided fractionation procedure through in vitro assays on cell viability and HSV-2 and RSV inhibition. S. desoleana EO inhibits both acyclovir sensitive and acyclovir resistant HSV-2 strains with EC50 values of 23.72 μg/ml for the former and 28.57 μg/ml for the latter. Moreover, a significant suppression of HSV-2 replication was observed with an EC50 value of 33.01 μg/ml (95% CI: 26.26 to 41.49) when the EO was added post-infection. Among the fractions resulting from flash column chromatography on silica gel, the one containing 54% of germacrene D showed a similar spectrum of activity of S. desoleana EO with a stronger suppression in post-infection stage. These results indicated that S. desoleana EO can be of interest to develop new and alternative anti-HSV-2 products active also against acyclovir-resistant HSV-2 strains. PMID:28207861

Saharan dust contribution to PM levels: The EC LIFE+ DIAPASON project

NASA Astrophysics Data System (ADS)

Gobbi, G. P.; Wille, H.; Sozzi, R.; Angelini, F.; Barnaba, F.; Costabile, F.; Frey, S.; Bolignano, A.; Di Giosa, A.

2012-04-01

The contribution of Saharan-dust advections to both daily and annual PM average values can be significant all over Southern Europe. The most important effects of dust on the number of PM exceedances are mostly observed in polluted areas and large cities. While a wide literature exists documenting episodes of Saharan dust transport towards the Euro-Mediterranean region and Europe in general, a limited number of studies are still available providing statistically significant results on the impact of Saharan dust on the particulate matter loads over the continent. A four-year (2001-2004) study performed in Rome (Italy) found these events to contribute to the average ground PM10 with about 15±10 µg/m3 on about 17% of the days in a year. Since the PM10 yearly average of many traffic stations in Rome is close to 40 μg/m3, these events can cause the PM10 concentration to exceed air quality limit values (50 μg/m3 as daily average) set by the EU Air Quality Directive 2008/50/EC. Although the European legislation allows Member States to subtract the contribution of natural sources before counting PM10 exceedances, definition of an optimal methodology to quantitatively assess such contribution is still in progress. On the basis of the current European Guidelines on the assessment of natural contributions to PM, the DIAPASON project ("Desert-dust Impact on Air quality through model-Predictions and Advanced Sensors ObservatioNs", recently funded under the EC LIFE+ program) has been formulated to provide a robust, user-oriented methodology to assess the presence of desert dust and its contribution to PM levels. To this end, in addition to satellite-based data and model forecasts, the DIAPASON methodology will employ innovative and affordable technologies, partly prototyped within the project itself, as an operational Polarization Lidar-Ceilometer (laser radar) capable of detecting and profiling dust clouds from the ground up to 10 km altitude. The DIAPASON Project (2011

Conductivity and Thermal Studies on Plasticized Nano-Composite Solid Polymer Electrolyte, Peo: Ec: LiTf: Al2O3

NASA Astrophysics Data System (ADS)

Pitawala, H. M. J. C.; Dissanayake, M. A. K. L.; Seneviratne, V. A.

2006-06-01

Poly (ethylene oxide)-(PEO)-based composite polymer electrolytes are of great interest for solid-state-electrochemical devices. This paper presents the results of a preliminary study on electrical conductivity and thermal behavior (DSC) of composite polymer electrolytes (CPEs) containing PEO: LiCF3SO3 complexed with plasticizer (EC) and incorporating nano-sized particles of the ceramic filler Al2O3. Ionic conductivity enhancement in these electrolytes has been obtained by optimizing the combined effect of the plasticizer and the ceramic filler. Nano-composite, plasticized polymer electrolyte films (400-600μm) were prepared by common solvent casting method. It was revealed that the presence of the Al2O3 filler in PEO: LiTf polymer electrolyte significantly enhanced the ionic conductivity in the temperature range of interest, giving the maximum conductivity for (PEO)9LiTf+15 wt.% Al2O3 CPE [σRT (max)=2×10-5 S cm-1]. It was also observed that the addition of plasticizer (EC) to this electrolyte up to a concentration of 50 wt. % EC, showed a further conductivity enhancement [σRT (max) = 1.5×10-4 S cm-1]. It is suggested that the conductivity is enhanced mainly by two mechanisms. The plasticizer (EC) would directly contribute by reducing the crystallinity and increasing the amorphous phase content of the polymer electrolytes. The ceramic filler (Al2O3) would contribute to conductivity enhancement by creating additional sites to migrating ionic species through transient bonding with O/OH groups in the filler surface. The decrease of Tg values of plasticized CPE systems seen in the DSC thermograms points towards the improved segmental flexibility of polymer chains, increasing the mobility of conducting ions.

Cytotoxic, Virucidal, and Antiviral Activity of South American Plant and Algae Extracts

PubMed Central

Faral-Tello, Paula; Mirazo, Santiago; Dutra, Carmelo; Pérez, Andrés; Geis-Asteggiante, Lucía; Frabasile, Sandra; Koncke, Elina; Davyt, Danilo; Cavallaro, Lucía; Heinzen, Horacio; Arbiza, Juan

2012-01-01

Herpes simplex virus type 1 (HSV-1) infection has a prevalence of 70% in the human population. Treatment is based on acyclovir, valacyclovir, and foscarnet, three drugs that share the same mechanism of action and of which resistant strains have been isolated from patients. In this aspect, innovative drug therapies are required. Natural products offer unlimited opportunities for the discovery of antiviral compounds. In this study, 28 extracts corresponding to 24 plant species and 4 alga species were assayed in vitro to detect antiviral activity against HSV-1. Six of the methanolic extracts inactivated viral particles by direct interaction and 14 presented antiviral activity when incubated with cells already infected. Most interesting antiviral activity values obtained are those of Limonium brasiliense, Psidium guajava, and Phyllanthus niruri, which inhibit HSV-1 replication in vitro with 50% effective concentration (EC50) values of 185, 118, and 60 μg/mL, respectively. For these extracts toxicity values were calculated and therefore selectivity indexes (SI) obtained. Further characterization of the bioactive components of antiviral plants will pave the way for the discovery of new compounds against HSV-1. PMID:22619617

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.

AVP-IC50 Pred: Multiple machine learning techniques-based prediction of peptide antiviral activity in terms of half maximal inhibitory concentration (IC50).

PubMed

Qureshi, Abid; Tandon, Himani; Kumar, Manoj

2015-11-01

Peptide-based antiviral therapeutics has gradually paved their way into mainstream drug discovery research. Experimental determination of peptides' antiviral activity as expressed by their IC50 values involves a lot of effort. Therefore, we have developed "AVP-IC50 Pred," a regression-based algorithm to predict the antiviral activity in terms of IC50 values (μM). A total of 759 non-redundant peptides from AVPdb and HIPdb were divided into a training/test set having 683 peptides (T(683)) and a validation set with 76 independent peptides (V(76)) for evaluation. We utilized important peptide sequence features like amino-acid compositions, binary profile of N8-C8 residues, physicochemical properties and their hybrids. Four different machine learning techniques (MLTs) namely Support vector machine, Random Forest, Instance-based classifier, and K-Star were employed. During 10-fold cross validation, we achieved maximum Pearson correlation coefficients (PCCs) of 0.66, 0.64, 0.56, 0.55, respectively, for the above MLTs using the best combination of feature sets. All the predictive models also performed well on the independent validation dataset and achieved maximum PCCs of 0.74, 0.68, 0.59, 0.57, respectively, on the best combination of feature sets. The AVP-IC50 Pred web server is anticipated to assist the researchers working on antiviral therapeutics by enabling them to computationally screen many compounds and focus experimental validation on the most promising set of peptides, thus reducing cost and time efforts. The server is available at http://crdd.osdd.net/servers/ic50avp. © 2015 Wiley Periodicals, Inc.

A "TNM" classification system for cancer pain: the Edmonton Classification System for Cancer Pain (ECS-CP).

PubMed

Fainsinger, Robin L; Nekolaichuk, Cheryl L

2008-06-01

The purpose of this paper is to provide an overview of the development of a "TNM" cancer pain classification system for advanced cancer patients, the Edmonton Classification System for Cancer Pain (ECS-CP). Until we have a common international language to discuss cancer pain, understanding differences in clinical and research experience in opioid rotation and use remains problematic. The complexity of the cancer pain experience presents unique challenges for the classification of pain. To date, no universally accepted pain classification measure can accurately predict the complexity of pain management, particularly for patients with cancer pain that is difficult to treat. In response to this gap in clinical assessment, the Edmonton Staging System (ESS), a classification system for cancer pain, was developed. Difficulties in definitions and interpretation of some aspects of the ESS restricted acceptance and widespread use. Construct, inter-rater reliability, and predictive validity evidence have contributed to the development of the ECS-CP. The five features of the ECS-CP--Pain Mechanism, Incident Pain, Psychological Distress, Addictive Behavior and Cognitive Function--have demonstrated value in predicting pain management complexity. The development of a standardized classification system that is comprehensive, prognostic and simple to use could provide a common language for clinical management and research of cancer pain. An international study to assess the inter-rater reliability and predictive value of the ECS-CP is currently in progress.

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.

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

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.

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.

Bioassay-guided isolation of active principles from Nigerian medicinal plants identifies new trypanocides with low toxicity and no cross-resistance to diamidines and arsenicals.

PubMed

Ebiloma, Godwin Unekwuojo; Igoli, John Ogbaji; Katsoulis, Evangelos; Donachie, Anne-Marie; Eze, Anthonius; Gray, Alexander Ian; de Koning, Harry P

2017-04-18

Leaves from the plant species studied herein are traditionally used in northern Nigeria against various protozoan infections. However, none of these herbal preparations have been standardized, nor have their toxicity to mammalian cells been investigated. In search of improved and non-toxic active antiprotozoal principles that are not cross-resistant with current anti-parasitics, we here report the results of the in vitro screening of extracts from seven selected medicinal plant species (Centrosema pubescens, Moringa oleifera, Tridax procumbens, Polyalthia longifolia, Newbouldia laevis, Eucalyptus maculate, Jathropha tanjorensis), used traditionally to treat kinetoplastid infections in Nigeria, and the isolation of their bioactive principles. To investigate the efficacies of medicinal plant extracts, and of compounds isolated therefrom, against kinetoplastid parasites, assess cross-resistance to existing chemotherapy, and assay their toxicity against mammalian cells in vitro. Plants were extracted with hexane, ethyl acetate and methanol. Active principles were isolated by bioassay-led fractionation, testing for trypanocidal activity, and identified using NMR and mass spectrometry. EC 50 values for their activity against wild-type and multi-drug resistant Trypanosoma brucei were obtained using the viability indicator dye resazurin. Seven medicinal plants were evaluated for activity against selected kinetoplastid parasites. The result shows that crude extracts and isolated active compounds from Polyalthia longifolia and Eucalyptus maculata, in particular, display promising activity against drug-sensitive and multi-drug resistant Trypanosoma brucei. The EC 50 value of a clerodane (16α-hydroxy-cleroda-3,13(14)-Z-dien-15,16-olide) isolated from Polyalthia longifolia was as low as 0.38µg/mL, while a triterpenoid (3β,13β-dihydroxy-urs-11-en-28-oic acid) isolated from Eucalyptus maculata displayed an EC 50 of 1.58µg/mL. None of the isolated compounds displayed toxicity

Pereskia aculeata Muller (Cactaceae) Leaves: Chemical Composition and Biological Activities

PubMed Central

Souza, Lucèia Fàtima; Caputo, Lucia; Inchausti De Barros, Ingrid Bergman; Fratianni, Florinda; Nazzaro, Filomena; De Feo, Vincenzo

2016-01-01

The aims of this work were to study the chemical composition of the essential oil from the leaves of Pereskia aculeata and to evaluate some biological activities of three leaf extracts. The phenolic content, antioxidant activity, and in vitro antimicrobial and antifungal activities were determined. The methanol extract showed antioxidant activity (EC50 7.09 mg/mL) and high polyphenols content (15.04 ± 0.31 mg gallic acid equivalents (GAE)/g). The petroleum ether extract exhibited potent antibacterial activity against Escherichia coli, whereas the chloroform extract showed inhibitory activity against Bacillus cereus and Staphylococcus aureus. The petroleum ether and methanol extracts were more effective in inhibiting the growth of Aspergillus versicolor. The possible cytotoxicity of extracts on neuroblastoma SH-SY5Y cancer cell line and the influence on adenylate cyclase (ADCY) expression was also studied. P. aculeata chloroform extract showed antiproliferative activity with an IC50 value of 262.83 µg/mL. Treatments of SH-SY5Y neuroblastoma cells with 100 µg/mL of methanol extract significantly reduced ADCY1 expression. PMID:27598154

Pereskia aculeata Muller (Cactaceae) Leaves: Chemical Composition and Biological Activities.

PubMed

Souza, Lucèia Fàtima; Caputo, Lucia; Inchausti De Barros, Ingrid Bergman; Fratianni, Florinda; Nazzaro, Filomena; De Feo, Vincenzo

2016-09-03

The aims of this work were to study the chemical composition of the essential oil from the leaves of Pereskia aculeata and to evaluate some biological activities of three leaf extracts. The phenolic content, antioxidant activity, and in vitro antimicrobial and antifungal activities were determined. The methanol extract showed antioxidant activity (EC50 7.09 mg/mL) and high polyphenols content (15.04 ± 0.31 mg gallic acid equivalents (GAE)/g). The petroleum ether extract exhibited potent antibacterial activity against Escherichia coli, whereas the chloroform extract showed inhibitory activity against Bacillus cereus and Staphylococcus aureus. The petroleum ether and methanol extracts were more effective in inhibiting the growth of Aspergillus versicolor. The possible cytotoxicity of extracts on neuroblastoma SH-SY5Y cancer cell line and the influence on adenylate cyclase (ADCY) expression was also studied. P. aculeata chloroform extract showed antiproliferative activity with an IC50 value of 262.83 µg/mL. Treatments of SH-SY5Y neuroblastoma cells with 100 µg/mL of methanol extract significantly reduced ADCY1 expression.

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

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

The binding of activated Gαq to phospholipase C-β exhibits anomalous affinity.

PubMed

Navaratnarajah, Punya; Gershenson, Anne; Ross, Elliott M

2017-10-06

Upon activation by the G q family of Gα subunits, Gβγ subunits, and some Rho family GTPases, phospholipase C-β (PLC-β) isoforms hydrolyze phosphatidylinositol 4,5-bisphosphate to the second messengers inositol 1,4,5-trisphosphate and diacylglycerol. PLC-β isoforms also function as GTPase-activating proteins, potentiating G q deactivation. To elucidate the mechanism of this mutual regulation, we measured the thermodynamics and kinetics of PLC-β3 binding to Gα q FRET and fluorescence correlation spectroscopy, two physically distinct methods, both yielded K d values of about 200 nm for PLC-β3-Gα q binding. This K d is 50-100 times greater than the EC 50 for Gα q -mediated PLC-β3 activation and for the Gα q GTPase-activating protein activity of PLC-β. The measured K d was not altered either by the presence of phospholipid vesicles, phosphatidylinositol 4,5-bisphosphate and Ca 2+ , or by the identity of the fluorescent labels. FRET-based kinetic measurements were also consistent with a K d of 200 nm We determined that PLC-β3 hysteresis, whereby PLC-β3 remains active for some time following either Gα q -PLC-β3 dissociation or PLC-β3-potentiated Gα q deactivation, is not sufficient to explain the observed discrepancy between EC 50 and K d These results indicate that the mechanism by which Gα q and PLC-β3 mutually regulate each other is far more complex than a simple, two-state allosteric model and instead is probably kinetically determined. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Structure-based design, synthesis, and biological evaluation of novel pyrrolyl aryl sulfones: HIV-1 non-nucleoside reverse transcriptase inhibitors active at nanomolar concentrations.

PubMed

Artico, M; Silvestri, R; Pagnozzi, E; Bruno, B; Novellino, E; Greco, G; Massa, S; Ettorre, A; Loi, A G; Scintu, F; La Colla, P

2000-05-04

Pyrrolyl aryl sulfones (PASs) have been recently reported as a new class of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitors acting at the non-nucleoside binding site of this enzyme (Artico, M.; et al. J. Med. Chem. 1996, 39, 522-530). Compound 3, the most potent inhibitor within the series (EC(50) = 0.14 microM, IC(50) = 0.4 microM, and SI > 1429), was then selected as a lead compound for a synthetic project based on molecular modeling studies. Using the three-dimensional structure of RT cocrystallized with the alpha-APA derivative R95845, we derived a model of the RT/3 complex by taking into account previously developed structure-activity relationships. Inspection of this model and docking calculations on virtual compounds prompted the design of novel PAS derivatives and related analogues. Our computational approach proved to be effective in making qualitative predictions, that is in discriminating active versus inactive compounds. Among the compounds synthesized and tested, 20 was the most active one, with EC(50) = 0.045 microM, IC(50) = 0.05 microM, and SI = 5333. Compared with the lead 3, these values represent a 3- and 8-fold improvement in the cell-based and enzyme assays, respectively, together with the highest selectivity achieved so far in the PAS series.

Efficacy of function specific 3D-motifs in enzyme classification according to their EC-numbers.

PubMed

Rahimi, Amir; Madadkar-Sobhani, Armin; Touserkani, Rouzbeh; Goliaei, Bahram

2013-11-07

Due to the increasing number of protein structures with unknown function originated from structural genomics projects, protein function prediction has become an important subject in bioinformatics. Among diverse function prediction methods, exploring known 3D-motifs, which are associated with functional elements in unknown protein structures is one of the most biologically meaningful methods. Homologous enzymes inherit such motifs in their active sites from common ancestors. However, slight differences in the properties of these motifs, results in variation in the reactions and substrates of the enzymes. In this study, we examined the possibility of discriminating highly related active site patterns according to their EC-numbers by 3D-motifs. For each EC-number, the spatial arrangement of an active site, which has minimum average distance to other active sites with the same function, was selected as a representative 3D-motif. In order to characterize the motifs, various points in active site elements were tested. The results demonstrated the possibility of predicting full EC-number of enzymes by 3D-motifs. However, the discriminating power of 3D-motifs varies among different enzyme families and depends on selecting the appropriate points and features. © 2013 Elsevier Ltd. All rights reserved.

Pharmacology of the human red cell voltage-dependent cation channel; Part I. Activation by clotrimazole and analogues.

PubMed

Barksmann, Trine L; Kristensen, Berit I; Christophersen, Palle; Bennekou, Poul

2004-01-01

The activation and pharmacological modulation of the nonselective voltage-dependent cation (NSVDC) channel from human erythrocytes were studied. Basic channel activation was achieved by suspending red cells in a low Cl(-) Ringer (2 mM), where a positive membrane potential (V(m) = E(Cl)) immediately developed. Voltage- and time-dependent activation of the NSVDC channel occurred, reaching a cation conductance (g+) of 1.5-2.0 microS cm(-2). In the presence of the classical Gárdos channel blocker clotrimazole (0-50 microM), activation occurred faster, and g+ saturated dose-dependently (EC50 = 14 microM) at a value of about 4 microS cm(-2). The clotrimazole analogues TRAM-34, econazole, and miconazole also stimulated the channel, whereas the chemically more distant Gárdos channel inhibitors nitrendipine and cetiedil had no effects. Although the potency for modulation of the NSVDC channel is much lower than the IC50 value for Gárdos channel inhibition, clotrimazole (and its analogues) constitutes the first chemical class of positive modulators of the NSVDC channel. This may be an important pharmacological "fingerprint" in the identification of the cloned equivalent of the erythrocyte channel.

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.

[Synthesis and biological activity of 2,3-secotriterpene acid mono- and diamides].

PubMed

Tolmacheva, I A; Igosheva, E V; Vikharev, Iu B; Grishko, V V; Savinova, O V; Boreko, E I; Eremin, V F

2013-01-01

Four types of amide (C3; C28; C3-C28) conjugates based on 2,3-seco-18alphaH-oleanane and 2,3-secolupane mono- and dicarboxylic acids were synthesized. The range of diamide derivatives was supplemented with C3-C3' and C28-C28' dicondensed amides with two A-secotriterpene backbones educed by reacting monocarboxylic A-secoacids with biogenic amino acid lysine. Compounds with inhibitory action against herpes virus reproduction (EC50 8.7 and 4.1 McM) were found among the synthesized mono- and diamide derivatives containing an ethyl-beta-alaninate fragment. It has been ascertained that diamide with ethyl-beta-alaninate fragment combines anti-herpes virus properties and anti-HIV activity (EC50 5.1 McM). For active compounds, the maximum non-toxic concentration (MNTC)/EC50 ratios ranges from 9.7 to 40.8. The synthesized amide conjugates do not exhibit any marked cytotoxic effects against human tumor cell lines rabdomiosarcoma RD TE32, A549 lung carcinoma and melanoma MS.

Can an endocytoscope system (ECS) predict histology in neoplastic lesions?

PubMed

Eberl, T; Jechart, G; Probst, A; Golczyk, M; Bittinger, M; Scheubel, R; Arnholdt, H; Knuechel, R; Messmann, H

2007-06-01

An endocytoscope system (ECS) has recently been developed with the possibility of super-high magnification of gastrointestinal mucosa, thus allowing in vivo imaging of living cells. The aim of the present study was to assess the potential of ECS in the prediction of histology in both normal gastrointestinal mucosa and neoplastic lesions. In total, 76 patients (57 men, 19 women; age range 37-86 years) with neoplastic lesions in the esophagus, stomach, or colon were enrolled into the study and underwent esophagogastroduodenoscopy or colonoscopy. After staining with 1% methylene blue, the mucosa was examined with the ECS probe (x 450 and x 1100 magnification), and video sequences were recorded on video disk. Biopsies from the examined areas were taken for histology and served as the gold standard. The endocytoscope video sequences were evaluated by two blinded pathologists. Finally the results were compared with those resulting from the evaluation of an experienced endoscopist who was aware of the macroscopic endoscopic pictures and the endocytoscope image results. A total of 25 patients with esophageal lesions, 28 patients with colonic lesions, and 23 patients with gastric lesions were examined. The sensitivity and specificity for the evaluation of the blinded pathologists was 81% and 100%, respectively, in the esophagus, 56% and 89% in the stomach, and 79% and 90% in the colon. If an endoscopist evaluated the endocytoscopic pictures in combination with the macroscopic endoscopic images sensitivity and specificity increased significantly. First experiences with ECS show good sensitivity rates even by blinded assessment for esophageal and colonic lesions. Sensitivity for neoplastic lesions in the stomach is lower because of gastric mucous secretion. Combining the endoscopic and cytoscopic appearance of the lesion may further enhance the diagnostic value of the method.

NP1EC Degradation Pathways Under Oxic and Microxic Conditions

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

Montgomery-Brown, John; Li, Yongmei; Ding, Wang-Hsien

2008-03-22

The degradation pathway of nonylphenol ethoxyacetic acid (NP1EC) and the conditions favoring CAP1EC formation were studied in aerobic microcosms constructed with soil from the Mesa soil aquifer treatment (SAT) facility (Arizona, USA) and pristine sediments from Coyote Creek (California, USA). In the Mesa microcosms, para-NP1EC was transformed to para-NP, before being rapidly transformed to nonyl alcohols via ipso-hydroxylation. While the formation of NP from APEMs has been observed by several researchers under anaerobic conditions, this is the first time the transient formation of NP from APEMs has been observed under aerobic conditions. Unlike the Mesa microcosms, large quantities of CAP1ECsmore » were observed in the Coyote Creek microcosms. Initially, CA8P1ECs were the dominant metabolites, but as biodegradation continued, CA6P1ECs became the dominant metabolites. Compared to the CA8P1ECs, the number of CA6P1ECs peaks observed was small (<6) even though their concentrations were high. This suggests that several CA8P1ECs are degraded to only a few CA6P1EC isomers (i.e., the degradation pathway converges) or that some CA6P1EC metabolites are significantly more recalcitrant than others. The different biodegradation pathways observed in the Mesa and Coyote Creek microcosms result from the limited availability of dissolved oxygen in the Coyote Creek microcosms. In both sets of microcosms, the ortho isomers were transformed more slowly than the para isomers and in the Coyote Creek microcosms several ortho-CAP1ECs were observed. In addition, several unknown metabolites were observed in the Coyote Creek microcosms that were not seen in the abiotic or Mesa microcosms; these metabolites appear to be CAP1EC metabolites, have a -CH2-C6H4- fragment, and contain one carboxylic acid. Nitro-nonylphenol was observed in the Mesa microcosms, however, further experimentation illustrated that it was the product of an abiotic reaction between nitrite and nonylphenol under acidic

The traditional use of Vachellia nilotica for sexually transmitted diseases is substantiated by the antiviral activity of its bark extract against sexually transmitted viruses.

PubMed

Donalisio, Manuela; Cagno, Valeria; Civra, Andrea; Gibellini, Davide; Musumeci, Giuseppina; Rittà, Massimo; Ghosh, Manik; Lembo, David

2018-03-01

Vachellia (Acacia) nilotica and other plants of this genus have been used in traditional medicine of Asian and African countries to treat many disorders, including sexually transmitted diseases, but few studies were performed to validate their anti-microbial and anti-viral activity against sexually transmitted infections. The present study was undertaken to explore whether the ethnomedical use of V.nilotica to treat genital lesions is substantiated by its antiviral activity against the human immunodeficiency virus (HIV), the herpes simplex virus (HSV) and the human papillomavirus (HPV). The antiviral activity of V.nilotica was tested in vitro by virus-specific inhibition assays using HSV-2 strains, sensible or resistant to acyclovir, HIV-1IIIb strain and HPV-16 pseudovirion (PsV). The potential mode of action of extract against HSV-2 and HPV-16 was further investigated by virus inactivation and time-of-addition assays on cell cultures. V.nilotica chloroform, methanolic and water bark extracts exerted antiviral activity against HSV-2 and HPV-16 PsV infections; among these, methanolic extract showed the best EC50s with values of 4.71 and 1.80µg/ml against HSV-2 and HPV-16, respectively, and it was also active against an acyclovir-resistant HSV-2 strain with an EC50 of 6.71µg/ml. By contrast, no suppression of HIV infection was observed. Investigation of the mechanism of action revealed that the methanolic extract directly inactivated the infectivity of the HPV-16 particles, whereas a partial virus inactivation and interference with virus attachment (EC50 of 2.74µg/ml) were both found to contribute to the anti-HSV-2 activity. These results support the traditional use of V.nilotica applied externally for the treatment of genital lesions. Further work remains to be done in order to identify the bioactive components. Copyright © 2017 Elsevier B.V. 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.

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

Activity inhibition on municipal activated sludge by single-walled carbon nanotubes

NASA Astrophysics Data System (ADS)

Parise, Alex; Thakor, Harshrajsinh; Zhang, Xiaoqi

2014-01-01

The objective of this study was to evaluate the respiratory activity inhibition of activated sludge used in a typical wastewater treatment plant by single-walled carbon nanotubes (SWCNTs) with different length and functionality. Four types of SWCNTs were evaluated: short, functionalized short, long, and functionalized long. Based on the effective concentration (EC50) values obtained, we determined that functionalized SWCNTs resulted in a higher microbial respiratory inhibition than non-functionalized nanotubes, and long SWCNTs gave a higher microbial respiratory inhibition than their short counterparts. Among the four types of SWCNTs studied, functionalized long exhibited the highest respiration inhibition. Scanning electron microscopy imaging indicates that the long SWCNTs dispersed more favorably after sonication than the short variety. The findings demonstrated that the toxicity of CNTs (exhibited by respiratory inhibition) is related to their physical properties; the length and functionality of SWCNTs affected the toxicity of SWCNTs in a mixed-cultured biologic system.

A preliminary investigation of the environmental Control and Life Support Subsystems (EC/LSS) for animal and plant experiment payloads

NASA Technical Reports Server (NTRS)

Wells, H. B.

1972-01-01

A preliminary study of the environmental control and life support subsystems (EC/LSS) necessary for an earth orbital spacecraft to conduct biological experiments is presented. The primary spacecraft models available for conducting these biological experiments are the space shuttle and modular space station. The experiments would be housed in a separate module that would be contained in either the shuttle payload bay or attached to the modular space station. This module would be manned only for experiment-related tasks, and would contain a separate EC/LSS for the crew and animals. Metabolic data were tabulated on various animals that are considered useful for a typical experiment program. The minimum payload for the 30-day space shuttle module was found to require about the equivalent of a one-man EC/LSS; however, the selected two-man shuttle assemblies will give a growth and contingency factor of about 50 percent. The maximum payloads for the space station mission will require at least a seven-man EC/LSS for the laboratory colony and a nine-man EC/LSS for the centrifuge colony. There is practically no room for growth or contingencies in these areas.

HPLC PROFILING OF PHENOLIC ACIDS AND FLAVONOIDS AND EVALUATION OF ANTI-LIPOXYGENASE AND ANTIOXIDANT ACTIVITIES OF AQUATIC VEGETABLE LIMNOCHARIS FLAVA.

PubMed

Ooh, Keng-fei; Ong, Hean-Chooi; Wong, Fai-Chu; Chai, Tsun-Thai

2015-01-01

Limnocharis flava is an edible wetland plant, whose phenolic acid and flavonoid compositions as well as bioactivities were underexplored. This study analyzed the profiles of selected hydroxybenzoic acids, hydroxycinnamic acids and flavonoids in the aqueous extracts of L. flava leaf, rhizome and root by high performance liquid chromatography (HPLC). Anti-lipoxygenase and antioxidant (iron chelating, 2,2-diphenyl-l-picrylhydrazyl (DPPH) radical scavenging, and nitric oxide (NO) scavenging) activities of the extracts were also evaluated. Leaf extract had the highest phenolic contents, being most abundant in p-hydroxybenzoic acid (3861.2 nmol/g dry matter), ferulic acid (648.8 nmol/g dry matter), and rutin (4110.7 nmol/g dry matter). Leaf extract exhibited the strongest anti-lipoxygenase (EC50 6.47 mg/mL), iron chelating (EC50 6.65 mg/mL), DPPH scavenging (EC50 15.82 mg/mL) and NO scavenging (EC50 3.80 mg/mL) activities. Leaf extract also had the highest ferric reducing ability. This is the most extensive HPLC profiling of phenolic acids and flavonoids in L.flava to date. In conclusion, L. flava leaf is a source of health-promoting phenolics, anti-lipoxygenase agents and antioxidants.

A Scalability Model for ECS's Data Server

NASA Technical Reports Server (NTRS)

Menasce, Daniel A.; Singhal, Mukesh

1998-01-01

This report presents in four chapters a model for the scalability analysis of the Data Server subsystem of the Earth Observing System Data and Information System (EOSDIS) Core System (ECS). The model analyzes if the planned architecture of the Data Server will support an increase in the workload with the possible upgrade and/or addition of processors, storage subsystems, and networks. The approaches in the report include a summary of the architecture of ECS's Data server as well as a high level description of the Ingest and Retrieval operations as they relate to ECS's Data Server. This description forms the basis for the development of the scalability model of the data server and the methodology used to solve it.

Structural basis of potassium activation in plant asparaginases.

PubMed

Ajewole, Ebenezer; Santamaria-Kisiel, Liliana; Pajak, Agnieszka; Jaskolski, Mariusz; Marsolais, Frédéric

2018-04-01

l-asparaginases (EC 3.5.1.1) play an important role in nitrogen mobilization in plants. Here, we investigated the biochemical and biophysical properties of potassium-dependent (PvAspG1) and potassium-independent (PvAspG-T2) l-asparaginases from Phaseolus vulgaris. Our previous studies revealed that PvAspG1 requires potassium for catalytic activation and its crystal structure suggested that Ser-118 in the activation loop plays a critical role in coordinating the metal cation. This amino acid residue is replaced by isoleucine in PvAspG-T2. Reciprocal mutants of the enzymes were produced and the effect of the amino acid substitution on the kinetic parameters, allosteric effector binding, secondary structure conformation, and pH profile were studied. Introduction of the serine residue conferred potassium activation in PvAspG-T2. Conversely, the PvAspG1-S118I mutant could no longer be activated by potassium. PvAspG1 and the PvAspG-T2-I117S mutant had a similar half-maximal effective concentration (EC 50 ) value for potassium activation, between 0.1 and 0.3 mm. Potassium binding elicited a similar conformational change in PvAspG1 and PvAspG-T2-I117S, as studied by circular dichroism. However, no change in conformation was observed for PvAspG-T2 and PvAspG1-S118I. Analysis of kinetic parameters in function of pH indicated that potassium activation mediated by Ser-118 influences the ionization of specific functional groups in the enzyme-substrate complex. Together, the results indicate that Ser-118 of PvAspG1 is essential and sufficient for potassium activation in plant l-asparaginases. ENZYME: l-Asparaginase (EC 3.5.1.1). © 2018 Federation of European Biochemical Societies.

Argonne's SpEC Module

ScienceCinema

Harper, Jason

2018-03-02

Jason Harper, an electrical engineer in Argonne National Laboratory's EV-Smart Grid Interoperability Center, discusses his SpEC Module invention that will enable fast charging of electric vehicles in under 15 minutes. The module has been licensed to BTCPower.

The influence of temperature calibration on the OC-EC results from a dual-optics thermal carbon analyzer

NASA Astrophysics Data System (ADS)

Pavlovic, J.; Kinsey, J. S.; Hays, M. D.

2014-09-01

Thermal-optical analysis (TOA) is a widely used technique that fractionates carbonaceous aerosol particles into organic and elemental carbon (OC and EC), or carbonate. Thermal sub-fractions of evolved OC and EC are also used for source identification and apportionment; thus, oven temperature accuracy during TOA analysis is essential. Evidence now indicates that the "actual" sample (filter) temperature and the temperature measured by the built-in oven thermocouple (or set-point temperature) can differ by as much as 50 °C. This difference can affect the OC-EC split point selection and consequently the OC and EC fraction and sub-fraction concentrations being reported, depending on the sample composition and in-use TOA method and instrument. The present study systematically investigates the influence of an oven temperature calibration procedure for TOA. A dual-optical carbon analyzer that simultaneously measures transmission and reflectance (TOT and TOR) is used, functioning under the conditions of both the National Institute of Occupational Safety and Health Method 5040 (NIOSH) and Interagency Monitoring of Protected Visual Environment (IMPROVE) protocols. The application of the oven calibration procedure to our dual-optics instrument significantly changed NIOSH 5040 carbon fractions (OC and EC) and the IMPROVE OC fraction. In addition, the well-known OC-EC split difference between NIOSH and IMPROVE methods is even further perturbed following the instrument calibration. Further study is needed to determine if the widespread application of this oven temperature calibration procedure will indeed improve accuracy and our ability to compare among carbonaceous aerosol studies that use TOA.

Is the Factor-of-2 Rule Broadly Applicable for Evaluating the Prediction Accuracy of Metal-Toxicity Models?

PubMed

Meyer, Joseph S; Traudt, Elizabeth M; Ranville, James F

2018-01-01

In aquatic toxicology, a toxicity-prediction model is generally deemed acceptable if its predicted median lethal concentrations (LC50 values) or median effect concentrations (EC50 values) are within a factor of 2 of their paired, observed LC50 or EC50 values. However, that rule of thumb is based on results from only two studies: multiple LC50 values for the fathead minnow (Pimephales promelas) exposed to Cu in one type of exposure water, and multiple EC50 values for Daphnia magna exposed to Zn in another type of exposure water. We tested whether the factor-of-2 rule of thumb also is supported in a different dataset in which D. magna were exposed separately to Cd, Cu, Ni, or Zn. Overall, the factor-of-2 rule of thumb appeared to be a good guide to evaluating the acceptability of a toxicity model's underprediction or overprediction of observed LC50 or EC50 values in these acute toxicity tests.

Antifouling and antipredatory activity of natural products of the seaweeds Dictyota dichotoma and Chaetomorpha linoides.

PubMed

Murugan, Annappan; Begum, Maraikayar Shynisha; Ramasamy, Maniramakrishnan Santhana; Raja, Paulraj

2012-01-01

The seaweeds Dictyota dichotoma and Chaetomorpha linoides from the southeast coast of India were screened for anti-microfouling activity against biofilm bacteria, anti-macrofouling activity against brown mussels and feeding deterrence activity against the sea angel Monodactylus kottelati. The surface associated epiphytic bacteria were also isolated from seaweeds and screened for activity against biofilm bacteria. The acetone extracts showed a wide spectrum activity against biofilm bacteria and the algal metabolite was surface concentrated and non-polar in nature. The seaweeds also inhibited byssus production and attachment in brown mussels, and deterred feeding in the sea angel. The lower epiphytic bacterial number on the seaweed's surface compared to the surrounding seawater medium indicated selective inhibition or surface mediation. The epiphytic bacteria, which showed activity against biofilm bacteria, might also possibly play a role in seaweed defence strategies. The 50% deterrence of feeding activity at lower concentrations was not proportionate to the 100% inhibition concentration, which could be attributed to the adaptability of the fishes, an indication that the active substances are inhibitory in nature. This was further substantiated with the 100% recovery of mussels in a toxicity assay and the lower EC(50) values than LC(50) values in the mussel bioassay. The study indicates that the metabolites of both seaweeds have ecological significance and could possibly play a multifunctional role.

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.

ECS - The European Communication Satellite system

NASA Astrophysics Data System (ADS)

Wooster, C. B.

1981-09-01

The evolution of the European Communication Satellite system (ECS) is traced from feasibility studies in 1970 to the development and launch in 1978 of the Orbital Test Satellite (OTS) by the European Space Agency to prove the new satellite and radio transmission technology being used on ECS. This was followed by the establishment of 'Interim EUTELSAT' in 1979 as the organization to operate ECS. The satellite, which operates at 11/14 GHz, covers all the capitals in Europe via three spot beam antennas, supplemented by a 'Eurobeam' regional coverage antenna which extends the range to cover all of Europe and the Mediterranean basin. Telephony channels are transmitted digitally using time division multiple access (TDMA) with digital speech interpolation (DSI) to optimize satellite capacity. Television transmission is by analog FM over the Eurobeam antenna to North African as well as European capitals. System implications of TDMA operation are discussed, and the EUTELSAT policy for Special Services or satellite business systems is discussed.

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.

Canatoxin, a toxic protein from jack beans (Canavalia ensiformis), is a variant form of urease (EC 3.5.1.5): biological effects of urease independent of its ureolytic activity.

PubMed Central

Follmer, C; Barcellos, G B; Zingali, R B; Machado, O L; Alves, E W; Barja-Fidalgo, C; Guimarães, J A; Carlini, C R

2001-01-01

Canatoxin is a toxic protein from Canavalia ensiformis seeds, lethal to mice (LD(50)=2 mg/kg) and insects. Further characterization of canatoxin showed that its main native form (184 kDa) is a non-covalently linked dimer of a 95 kDa polypeptide containing zinc and nickel. Partial sequencing of internal peptides indicated homology with urease (EC 3.5.1.5) from the same seed. Canatoxin has approx. 30% of urease's activity for urea, and K(m) of 2-7 mM. The proteins differ in their affinities for metal ions and were separated by affinity chromatography on a Zn(2+) matrix. Similar to canatoxin, urease activates blood platelets and interacts with glycoconjugates. In contrast with canatoxin, no lethality was seen in mice injected with urease (10 mg/kg). Pretreatment with p-hydroxymercuribenzoate irreversibly abolished the ureolytic activity of both proteins. On the other hand, p-hydroxymercuribenzoate-treated canatoxin was still lethal to mice, and both treated proteins were fully active in promoting platelet aggregation and binding to glycoconjugates. Taken together, our data indicate that canatoxin is a variant form of urease. Moreover, we show for the first time that these proteins display several biological effects that are unrelated to their enzymic activity for urea. PMID:11696010

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.

ECS DAAC Data Pools

NASA Astrophysics Data System (ADS)

Kiebuzinski, A. B.; Bories, C. M.; Kalluri, S.

2002-12-01

As part of its Earth Observing System (EOS), NASA supports operations for several satellites including Landsat 7, Terra, and Aqua. ECS (EOSDIS Core System) is a vast archival and distribution system and includes several Distributed Active Archive Centers (DAACs) located around the United States. EOSDIS reached a milestone in February when its data holdings exceeded one petabyte (1,000 terabytes) in size. It has been operational since 1999 and originally was intended to serve a large community of Earth Science researchers studying global climate change. The Synergy Program was initiated in 2000 with the purpose of exploring and expanding the use of remote sensing data beyond the traditional research community to the applications community including natural resource managers, disaster/emergency managers, urban planners and others. This included facilitating data access at the DAACs to enable non-researchers to exploit the data for their specific applications. The combined volume of data archived daily across the DAACs is of the order of three terabytes. These archived data are made available to the research community and to general users of ECS data. Currently, the average data volume distributed daily is two terabytes, which combined with an ever-increasing need for timely access to these data, taxes the ECS processing and archival resources for more real-time use than was previously intended for research purposes. As a result, the delivery of data sets to users was being delayed in many cases, to unacceptable limits. Raytheon, under the auspices of the Synergy Program, investigated methods at making data more accessible at a lower cost of resources (processing and archival) at the DAACs. Large on-line caches (as big as 70 Terabytes) of data were determined to be a solution that would allow users who require contemporary data to access them without having to pull it from the archive. These on-line caches are referred to as "Data Pools." In the Data Pool concept

On the isolation of elemental carbon (EC) for micro-molar 14C accelerator mass spectrometry: development of a hybrid reference material for 14C-EC accuracy assurance, and a critical evaluation of the thermal optical kinetic (TOK) EC isolation procedure

NASA Astrophysics Data System (ADS)

Currie, L. A.; Kessler, J. D.

2005-10-01

The primary objective of the research reported here has been the development of a hybrid reference material (RM) to serve as a test of accuracy for elemental carbon (EC) isotopic (14C) speciation measurements. Such measurements are vital for the quantitative apportionment of fossil and biomass sources of "soot" (EC), the tracer of fire that has profound effects on health, atmospheric visibility, and climate. Previous studies of 14C-EC measurement quality, carried out with NIST SRM 1649a (Urban Dust), showed a range of results, but since the "truth" was not known for this natural matrix RM, one had to rely on isotopic-chemical consistency evidence (14C in PAH, EC) of measurement validity (Currie et al., 2002). Components of the new Hybrid RM (DiesApple), however, have known 14C and EC composition, and they are nearly orthogonal (isotopically and chemically). NIST SRM 2975 (Forklift Diesel Soot) has little or no 14C, and its major compositional component is EC; SRM 1515 (Apple Leaves) has the 14C content of biomass-C, and it has little or no EC. Thus, the Hybrid RM can serve as an absolute isotopic test for the absence of EC-mimicking pyrolysis-C (char) from SRM 1515 in the EC isolate of the Hybrid RM, as well as a test for conservation of its dominant soot fraction throughout the isolation procedure.

The secondary objective was to employ the Hybrid RM for the comparative evaluation of the thermal optical kinetic (TOK) and thermal optical transmission (TOT) methods for the isolation of EC for micro-molar carbon accelerator mass spectrometry (AMS). As part of this process, the relatively new TOK method was subjected to a critical evaluation and significant development. Key findings of our study are: (1) both methods exhibited biomass-C "leakage"; for TOT, the EC fraction isolated for AMS contained about 8% of the original biomass-C; for TOK, the refractory carbon (RC) isolated contained about 3% of the original biomass-C.; (2) the

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.

Rational screening of peroxisome proliferator-activated receptor-γ agonists from natural products: potential therapeutics for heart failure.

PubMed

Chen, Rui; Wan, Jing; Song, Jing; Qian, Yan; Liu, Yong; Gu, Shuiming

2017-12-01

Peroxisome proliferator-activated receptor-γ (PPARγ) is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors. Activation of PPARγ pathway has been shown to enhance fatty acid oxidation, improve endothelial cell function, and decrease myocardial fibrosis in heart failure. Thus, the protein has been raised as an attractive target for heart failure therapy. This work attempted to discover new and potent PPARγ agonists from natural products using a synthetic strategy of computer virtual screening and transactivation reporter assay. A large library of structurally diverse, drug-like natural products was compiled, from which those with unsatisfactory pharmacokinetic profile and/or structurally redundant compounds were excluded. The binding mode of remaining candidates to PPARγ ligand-binding domain (LBD) was computationally modelled using molecular docking and their relative binding potency was ranked by an empirical scoring scheme. Consequently, eight commercially available hits with top scores were selected and their biological activity was determined using a cell-based reporter-gene assay. Four natural product compounds, namely ZINC13408172, ZINC4292805, ZINC44179 and ZINC901461, were identified to have high or moderate agonistic potency against human PPARγ with EC 50 values of 0.084, 2.1, 0.35 and 5.6 μM, respectively, which are comparable to or even better than that of the approved PPARγ full agonists pioglitazone (EC 50  =   0.16 μM) and rosiglitazone (EC 50  =   0.034 μM). Hydrophobic interactions and van der Waals contacts are the primary chemical forces to stabilize the complex architecture of PPARγ LBD domain with these agonist ligands, while few hydrogen bonds, salt bridges and/or π-π stacking at the complex interfaces confer selectivity and specificity for the domain-agonist recognition. The integrated in vitro-in silico screening strategy can be successfully applied to rational discovery of

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.

Endocrine activity in an urban river system and the biodegradation of estrogen-like endocrine disrupting chemicals through a bio-analytical approach using DRE- and ERE-CALUX bioassays.

PubMed

Vandermarken, T; Croes, K; Van Langenhove, K; Boonen, I; Servais, P; Garcia-Armisen, T; Brion, N; Denison, M S; Goeyens, L; Elskens, M

2018-06-01

The Zenne River, crossing the Brussels region (Belgium) is an extremely urbanized river impacted by both domestic and industrial effluents. The objective of this study was to monitor the occurrence and activity of Endocrine Active Substances (EAS) in river water and sediments in the framework of the Environmental Quality Standards Directive (2008/105/EC and 2013/39/EU). Activities were determined using Estrogen and Dioxin Responsive Elements (ERE and DRE) Chemical Activated Luciferase Gene Expression (CALUX) bioassays. A potential contamination source of estrogen active compounds was identified in the river at an industrial area downstream from Brussels with a peak value of 938 pg E2 eq./L water (above the EQS of 0.4 ng/L) and 195 pg E2 eq./g sediment. Estrogens are more abundantly present in the sediments than in the dissolved phase. Principal Component Analysis (PCA) showed high correlations between Suspended Particulate Matter (SPM), Particulate (POC) and Dissolved Organic Carbon (DOC) and estrogenic EAS. The dioxin fractions comply with previous data and all were above the United States Environmental Protection Agency (US EPA) low-level risk, with one (42 pg TCDD eq./g sediment) exceeding the high-level risk value for mammals. The self-purifying ability of the Zenne River regarding estrogens was examined with an in vitro biodegradation experiment using the bacterial community naturally present in the river. Hill coefficient and EC 50 values (Effective Concentration at 50%) revealed a process of biodegradation in particulate and dissolved phase. The estrogenic activity was decreased by 80%, demonstrating the ability of self-purification of estrogenic compounds in the Zenne River. Copyright © 2018 Elsevier Ltd. All rights reserved.

Achievements and bottlenecks in humanitarian demining EU-funded research: final results from the EC DELVE project

NASA Astrophysics Data System (ADS)

Sahli, Hichem; Bruschini, Claudio; Van Kempen, Luc; Schleijpen, Ric; den Breejen, Eric

2008-04-01

The EC DELVE Support Action project has analyzed the bottlenecks in the transfer of Humanitarian Demining (HD) technology from technology development to the use in the field, and drawn some lessons learned, basing itself on the assessment of the European Humanitarian Demining Research and Technology Development (RTD) situation from early 1990 until 2006. The situation at the European level was analyzed with emphasis on activities sponsored by the European Commission (EC). This was also done for four European countries and Japan, with emphasis on national activities. The developments in HD during the last 10 years underline the fact that in a number of cases demining related developments have been terminated or at least put on hold. The study also showed that the funding provided by the EC under the Framework Program for RTD has led directly to the creation of an extensive portfolio of Humanitarian Demining technology development projects. The latter provided a range of research and supporting measures addressing the critical issues identified as a result of the regulatory policies developed in the field of Humanitarian Demining over the last ten years. However, the range of instruments available to the EC to finance the necessary research and development were limited, to pre-competitive research. The EC had no tools or programs to directly fund actual product development. As a first consequence, the EC funding program for development of technology for Humanitarian Demining unfortunately proved to be largely unsuitable for the small-scale development needed in a field where there is only a very limited market. As a second consequence, most of the research has been demonstrator-oriented. Moreover, the timeframe for RTD in Humanitarian Demining has not been sufficiently synchronized with the timeframe of the EC policies and regulations. The separation of the Mine Action and RTD funding streams in the EC did also negatively affect the take-up of new technologies. As a

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

Mosquitocidal Activity and Mode of Action of the Isoxazoline Fluralaner.

PubMed

Jiang, Shiyao; Tsikolia, Maia; Bernier, Ulrich R; Bloomquist, Jeffrey R

2017-02-06

Mosquitoes, such as Aedes aegypti and Anopheles gambiae , are important vectors of human diseases. Fluralaner, a recently introduced parasiticide, was evaluated as a mosquitocide in this study. On Ae. aegypti and An. gambiae fourth-instar larvae, fluralaner had 24-h LC 50 (lethal concentration for 50% mortality) values of 1.8 ppb and 0.4 ppb, respectively. Following topical application to adult Ae. aegypti , fluralaner toxicity reached a plateau in about 3 days, with 1- and 3-day LD 50 (lethal dose for 50% mortality) values of 1.3 ng/mg and 0.26 ng/mg, suggesting a slowly developing toxicity. Fipronil outperformed fluralaner by up to 100-fold in adult topical, glass contact, and feeding assays on Ae. aegypti . These data show that fluralaner does not have exceptional toxicity to mosquitoes in typical exposure paradigms. In electrophysiological recordings on Drosophila melanogaster larval central nervous system, the effectiveness of fluralaner for restoring nerve firing after gamma-aminobutyric acid (GABA) treatment, a measure of GABA antagonism, was similar in susceptible Oregon-R and cyclodiene-resistant rdl -1675 strains, with EC 50 (half maximal effective concentration) values of 0.34 µM and 0.29 µM. Although this finding suggests low cross resistance in the presence of rdl , the moderate potency, low contact activity, and slow action of fluralaner argue against its use as an adult mosquitocide for vector control.

Mosquitocidal Activity and Mode of Action of the Isoxazoline Fluralaner

PubMed Central

Jiang, Shiyao; Tsikolia, Maia; Bernier, Ulrich R.; Bloomquist, Jeffrey R.

2017-01-01

Mosquitoes, such as Aedes aegypti and Anopheles gambiae, are important vectors of human diseases. Fluralaner, a recently introduced parasiticide, was evaluated as a mosquitocide in this study. On Ae. aegypti and An. gambiae fourth-instar larvae, fluralaner had 24-h LC50 (lethal concentration for 50% mortality) values of 1.8 ppb and 0.4 ppb, respectively. Following topical application to adult Ae. aegypti, fluralaner toxicity reached a plateau in about 3 days, with 1- and 3-day LD50 (lethal dose for 50% mortality) values of 1.3 ng/mg and 0.26 ng/mg, suggesting a slowly developing toxicity. Fipronil outperformed fluralaner by up to 100-fold in adult topical, glass contact, and feeding assays on Ae. aegypti. These data show that fluralaner does not have exceptional toxicity to mosquitoes in typical exposure paradigms. In electrophysiological recordings on Drosophila melanogaster larval central nervous system, the effectiveness of fluralaner for restoring nerve firing after gamma-aminobutyric acid (GABA) treatment, a measure of GABA antagonism, was similar in susceptible Oregon-R and cyclodiene-resistant rdl-1675 strains, with EC50 (half maximal effective concentration) values of 0.34 µM and 0.29 µM. Although this finding suggests low cross resistance in the presence of rdl, the moderate potency, low contact activity, and slow action of fluralaner argue against its use as an adult mosquitocide for vector control. PMID:28178191

Isoprenylated flavonoids from the root bark of Morus alba and their hepatoprotective and neuroprotective activities.

PubMed

Jung, Jae-Woo; Ko, Won-Min; Park, Ji-Hae; Seo, Kyeong-Hwa; Oh, Eun-Ji; Lee, Dae-Young; Lee, Dong-Sung; Kim, Youn-Chul; Lim, Dong-Wook; Han, Daeseok; Baek, Nam-In

2015-11-01

A new isoprenylated flavonoid, 2S-5,7,2',4'-tetrahydroxy-3',5'-di-(γ,γ-dimethylallyl)flavanone, sanggenol Q (1), along with seven known isoprenylated flavonoids, sanggenol A (2), sanggenol L (3), kuwanon T (4), cyclomorusin (5), sanggenon F (6), sanggenol O (7), and sanggenon N (8), three known Diels-Alder type adducts, sanggenon G (9), mulberrofuran G (10), and mulberrofuran C (11), and a known benzofuran, moracin E (12), were isolated from the root bark of Morus alba using silica gel, ODS, and Sephadex LH-20 column chromatography. Chemical structures were determined based on spectroscopic data analyses including NMR, MS, CD, and IR. For the first time, compounds 1 and 7 were isolated from the root bark of M. alba. All compounds were evaluated for hepatoprotective activity on t-BHP-induced oxidative stress in HepG2 cells and neuroprotective activity on glutamate-induced cell death in HT22 cells. Compounds 1, 4, 8, 10, and 11 showed protective effects on t-BHP-induced oxidative stress with EC50 values of 6.94 ± 0.38, 30.32 ± 6.82, 23.45 ± 4.72, 15.31 ± 2.21, and 0.41 ± 0.48 μM, respectively, and compounds 1, 2, 10, 11, and 12 showed protective effects on glutamate-induced cell death with EC50 values of 5.54 ± 0.86, 34.03 ± 7.71, 19.71 ± 0.71, 16.50 ± 7.82, and 1.02 ± 0.13 μM, respectively.

The effect of tributyltin-oxide on earthworms, springtails, and plants in artificial and natural soils.

PubMed

Römbke, J; Jänsch, S; Junker, T; Pohl, B; Scheffczyk, A; Schallnass, H-J

2007-05-01

Chemical bioavailability in Organisation for Economic Co-operation and Development (OECD) artificial soil can contrast with bioavailability in natural soils and produce ecotoxicologic benchmarks that are not representative of species' exposure conditions in the field. Initially, reproduction and growth of earthworm and Collembolan species, and early seedling growth of a dicotyledonous plant species, in nine natural soils (with a wide range of physicochemical properties) and in OECD soil were evaluated. Soils that supported reproduction and growth of the test species were then used to investigate the toxicity of tributyltin-oxide (TBT-O). Natural soils caused greater toxicity of TBT-O to earthworms (EC(50) values varied from 0.5 to 4.7 mg/kg soil dry weight [dw]) compared with toxicity in OECD soil (EC(50) = 13.4 mg/kg dw). Collembolans were less sensitive to TBT-O than earthworms in natural soils, with EC(50) values ranging from 23.4 to 177.8 mg/kg dw. In contrast, the toxicity of TBT-O to collembolans in OECD soil (EC(50) = 104.0 mg/kg dw) was within the range of EC(50) values in natural soils. Phytotoxicity tests revealed even greater difference between the effects in natural soils (EC(50) values ranged from 10.7 to 189.2 mg/kg dw) and in OECD soil (EC(50) = 535.5 mg/kg dw) compared with results of the earthworm tests. Studies also showed that EC(50) values were a more robust end point compared with EC(10) values based on comparisons of coefficients of variation. These results show that toxicity testing should include studies with natural soils in addition to OECD soil to better reflect exposure conditions in the field.

Comparative antioxidant activity of cultivated and wild Vaccinium species investigated by EPR, human neutrophil burst and COMET assay.

PubMed

Braga, P C; Antonacci, R; Wang, Y Y; Lattuada, N; Dal Sasso, M; Marabini, L; Fibiani, M; Lo Scalzo, R

2013-01-01

The Vaccinium (V.) spp. berries are considered a source of antioxidants, mainly belonging to polyphenols, specifically flavonoids and anthocyanins. Wild genotypes generally contain more antioxidants than cultivated counterparts. So, seven different antioxidants assays on extracts from cultivated and wild Vaccinium berries were performed, to evaluate their difference in terms of bioactivity on oxidative protection and minimum dosage to have a significant action. Four cell-free antioxidant assays (ABTS radical scavenging and electronic paramagnetic resonance using Fremy's salt, superoxide anion and hydroxyl radical), and three assays on human cells (two luminol amplified chemiluminescence, LACL, one on DNA damage, COMET) were used to measure the effects of cultivated blueberry (V. corymbosum) and wild bilberry (V. myrtillus) on the differently induced oxidative stress. Concentrations vs activity patterns were obtained by successive dilutions of extracts in order to identify both EC50 and minimum significant activity (MSA). All the assays (except for the hydroxyl radical scavenging) showed a good relationship mainly with anthocyanin and polyphenol content and the significant greater activity of wild Vaccinium extracts. In fact, LACL data gave an EC50 of 11.8 and an MSA of 5.2 g were calculated as fresh weight dosage in cultivated berries, compared with lower doses in wild berries, EC50 of 5.7 g and MSA of 3.4 g. Wild Vaccinium extracts averaged 3.04 and 2.40 fold more activity than cultivated extracts by EC50 and MSA, respectively. COMET assay confirmed the stronger action on DNA protection in wild samples.

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.

Leishmanicidal activity of Nystatin (mycostatin): a potent polyene compound.

PubMed

Ali, S A; Iqbal, J; Nabeel; Khalil, Y; Manzoor, A; Bukhari, I; Ahmad, B; Yasinzai, M M

1997-10-01

The susceptibility of promastigote of Leishmania major to Nystatin in vitro was examined. L. major (MHOM/PK/88/DESTO) promastigote were cultured in medium 199 supplemented with 10% heat inactivated foetal bovine serum and 2% urine. The growth of the promastigote was monitored in the absence and presence of the experimental compound (Nystatin) for upto 5 days post-inoculation. The EC50 value (the concentration of drug necessary to inhibit the growth rate of cells to 50% of the control value) obtained for Nystatin against the promastigote of L. major was less than 9.76 iu ml. Certain polyene compounds like Amphotericin-B and Nystatin (mycostatin) are familiar for their fungicidal activity. Amphotericin-B is used since long as antileishmanial drug as well. Results obtained suggest that Nystatin has a very good anti leishmanial activity in vitro. The mode of action proposed for this drug is same as for Amphotericin-B as both of these polyene compounds interact with the various sterols present on the surface of the parasite, thus unusual gaps and pores are formed on the surface that results in the leakage of the ions. This leakage finally leads to the destruction of the parasite.

Degradation of phosphorylated p53 by viral protein-ECS E3 ligase complex.

PubMed

Sato, Yoshitaka; Kamura, Takumi; Shirata, Noriko; Murata, Takayuki; Kudoh, Ayumi; Iwahori, Satoko; Nakayama, Sanae; Isomura, Hiroki; Nishiyama, Yukihiro; Tsurumi, Tatsuya

2009-07-01

p53-signaling is modulated by viruses to establish a host cellular environment advantageous for their propagation. The Epstein-Barr virus (EBV) lytic program induces phosphorylation of p53, which prevents interaction with MDM2. Here, we show that induction of EBV lytic program leads to degradation of p53 via an ubiquitin-proteasome pathway independent of MDM2. The BZLF1 protein directly functions as an adaptor component of the ECS (Elongin B/C-Cul2/5-SOCS-box protein) ubiquitin ligase complex targeting p53 for degradation. Intringuingly, C-terminal phosphorylation of p53 resulting from activated DNA damage response by viral lytic replication enhances its binding to BZLF1 protein. Purified BZLF1 protein-associated ECS could be shown to catalyze ubiquitination of phospho-mimetic p53 more efficiently than the wild-type in vitro. The compensation of p53 at middle and late stages of the lytic infection inhibits viral DNA replication and production during lytic infection, suggesting that the degradation of p53 is required for efficient viral propagation. Taken together, these findings demonstrate a role for the BZLF1 protein-associated ECS ligase complex in regulation of p53 phosphorylated by activated DNA damage signaling during viral lytic infection.

Novel biotransformation process of podophyllotoxin to 4 β-sulfur-substituted podophyllum derivates with anti-tumor activity by Penicillium purpurogenum Y.J. Tang.

PubMed

Bai, J-K; Zhao, W; Li, H-M; Tang, Y-J

2012-01-01

According to the structure-function relationship of podophyllotoxin (PTOX) and its analogue of 4'- demethylepipodophyllotoxin (DMEP), the 4 β-substitution of sulfur-containing heterocyclic compounds with a carbon-sulfur bond at 4 position of PTOX or DMEP is an essential modification direction for improving the anti-tumor activity. So, four novel 4 β-sulfursubstituted podophyllum derivatives (i.e., 4β -(1,2,4-triazole-3-yl)sulfanyl-4-deoxy-podophyllotoxin (4-MT-PTOX), 4β-(1,3,4- thiadiazole-2-yl)sulfanyl-4-deoxy-podophyllotoxin (4-MTD-PTOX), 4β-(1,2,4-triazole-3-yl)sulfanyl-4-deoxy-4' -demethylepipodophyllotoxin (4-MT-DMEP), and 4β-(1,3,4-thiadiazole-2-yl)sulfanyl-4-deoxy-4'-demethylepipodophyllotoxin (4-MTD-DMEP)) were designed and then successfully biosynthesized in this work. In the novel sulfur-substituted biotransformation processes, PTOX and DMEP was linked with sulfur-containing compounds (i.e., 3-mercapto-1,2,4-triazole (MT) and 2-mercapto-1,3,4-thiadiazole (MTD)) at 4 position of cycloparaffin to produce 4-MT-PTOX (1), 4-MTD-PTOX (2), 4-MT-DMEP (3), and 4-MTD-DMEP (4) by Penicillium purpurogenum Y.J. Tang, respectively, which was screened out from Diphylleia sinensis Li (Hubei, China). All the novel compounds exhibited promising in vitro bioactivity, especially 4-MT-PTOX (1). Compared with etoposide (i.e., a 50 % effective concentration [EC(50)] of 25.72, 167.97, and 1.15 M), the EC(50) values of 4-MT-PTOX (1) against tumor cell line BGC-823, A549 and HepG2 (i.e., 0.28, 0.76, and 0.42 M) were significantly improved by 91, 221 and 2.73 times, respectively. Moreover, the EC(50) value of 4-MT-PTOX (1) against the normal human cell line HK-2 (i.e., 182.4 μM) was 19 times higher than that of etoposide (i.e., 9.17 μM). Based on the rational design, four novel 4 β-sulfur-substituted podophyllum derivatives with superior in vitro anti-tumor activity were obtained for the first time. The correctness of structure-function relationship and rational drug

Repeated electroconvulsive shock (ECS) alters the phosphorylation of glutamate receptor subunits in the rat hippocampus.

PubMed

Fumagalli, Fabio; Pasini, Matteo; Sartorius, Alexander; Scherer, Rosine; Racagni, Giorgio; Riva, Marco A; Gass, Peter

2010-10-01

Glutamate and its receptors are involved in the pathophysiology of mood disorders and have recently emerged as potential targets for the pharmacotherapy of depression. In rats, we investigated plasticity changes of the glutamatergic system evoked by electroconvulsive shock (ECS), which represents the most effective therapy for patients who are refractory to antidepressants. Chronic ECS produced a marked increase in the phosphorylation of the regulatory NMDA receptor subunit NR2B (Ser1303) and the AMPA receptor subunit GluR-A (Ser831) in the hippocampus, with no effects on the obligatory subunit NR1. No effects were found on total receptor subunit expression levels. We suggest that, at least in part, ECS exerts its clinical activity through the modulation of the glutamatergic synapses, via potentiation of AMPA currents mediated by GluR-A (Ser831) phosphorylation, and a reduction of NMDA receptor activity through the phosphorylation of NR2B (Ser1303), presumably uncoupling NR2B from its signalling partner CaMKII. These effects functionally resemble the recently described antidepressant effects of ketamine.

Probing the Interaction between Cyclic ADTC1 Ac-CADTPPVC-NH2) Peptide with EC1-EC2 domain of E-cadherin using Molecular Docking Approach

NASA Astrophysics Data System (ADS)

Siahaan, P.; Wuning, S.; Manna, A.; Prasasty, V. D.; Hudiyanti, D.

2018-04-01

Deeply understanding that intermolecular interaction between molecules on the paracellular pathway has given insight to its microscopic and macroscopic properties. In the paracellular pathway, synthetic cyclic ADTC1 (Ac-CADTPPVC-NH2) peptide has been studied to modulate EC1-EC2 domain, computationally using molecular docking method. The aim of this research is to probe the effect of amino acid alanine (A) of ADTC1 on its interaction properties. The study carried out in two steps: 1. the optimization using GROMACS v4.6.5 program and; 2. Determination of the interaction properties using AutoDock 4.2 program. The interaction was done for A-J box, and the best position of the binding site and binding energy on the OC and CC ADTC1 peptides against the EC1-EC2 domain of E-cadherin was selected. The result showed that the CC of the F box ADTC1 has the best interaction with binding energy of - 26.36 kJ/mol and its energy was lower than ADTC5 without alanine amino acid. ADTC1 interacted with EC1 of EC1-EC2 on Asp1, Trp2, Val3, Ile4, Ile24, Lys25, Ser26, Asn27, and Met92 residues.

Spermicidal activity of Indian seaweeds: an in vitro study.

PubMed

Prakash, S; Ravikumar, S; Reddy, K V R; Kannapiran, E

2014-05-01

Contraceptive properties of seaweeds are still stands as lacuna; in this context, the screening of in vitro male contraceptive properties of crude ethanolic extract of Indian seaweeds against normal human sperm is carried out. In total, twelve seaweeds were screened for in vitro spermicidal activity. Among these twelve seaweeds, Halimeda gracilis showed 100% inhibition of human spermatozoa at 10 mg ml(-1) concentration in 20 s and its EC50 value was 2.05 mg ml(-1) in 20 s. Further, dose- and time-dependent spermicidal assay revealed that the sperm was completely immobilised for 20 s. Plasma membrane of sperm was damaged due to the exposure of H. gracilis extract. MTT assay with H. gracilis extract showed 88.5% of cytotoxic incidence. H. gracilis extract tested for cytotoxicity against Artemia salina recorded LC50 value of 34.8 μg ml(-1) . Phytochemical analysis of H. gracilis extract evidenced the presence of alkaloids, flavonoids, proteins and sugars. Results of this study clearly inferred that the synergistic effect of active principles reside within the H. gracilis extract had shown better contraceptive activity. © 2013 Blackwell Verlag GmbH.

Discovery, synthesis, and structure-activity relationships of 20(S)-protopanaxadiol (PPD) derivatives as a novel class of AMPKα2β1γ1 activators.

PubMed

Liu, Junhua; Chen, Dakai; Liu, Peng; He, Mengna; Li, Jia; Li, Jingya; Hu, Lihong

2014-05-22

Adenosine 5'-monophosphate-activated protein kinase (AMPK) has been demonstrated as a promising drug target due to its regulatory function in glucose and lipid metabolism. 20(S)-protopanoxadiol (PPD) was firstly identified from high throughput screening as a small molecule activator of AMPK subtype α2β1γ1. In order to enhance its potency on AMPK, a series of PPD derivatives were synthesized and evaluated. Structure-activity relationship study showed that the amine derivatives at the 24-position (groups I-VI) can improve the potency (EC50: 0.7-2.3 μM) and efficacy (fold: 2.5-3.8). Among them, compounds 12 and 13 exhibited the best potency (EC50: 1.2 and 0.7 μM) and efficacy (fold: 3.7 and 3.8). Further study suggested the mechanism of AMPK activation may functioned at the allosteric position, resulting the inhibition of the lipid synthesis in HepG2 cell model. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Differential neurophysiological effects of magnetic seizure therapy (MST) and electroconvulsive shock (ECS) in non-human primates.

PubMed

Cycowicz, Yael M; Luber, Bruce; Spellman, Timothy; Lisanby, Sarah H

2008-07-01

Magnetic seizure therapy (MST) is under development as a means of reducing the side effects of electroconvulsive therapy (ECT) through enhanced control over patterns of seizure induction and spread. We previously reported that chronic treatment with MST resulted in less impairment in cognitive function than electroconvulsive shock (ECS) in a non-human primate model of convulsive therapy. Here we present quantitative analyses of ictal expression and post-ictal suppression following ECS, MST, and anesthesia-alone sham in the same model to test whether differential neurophysiological characteristics of the seizures could be identified. Rhesus monkeys received 4 weeks of daily treatment with ECS, MST, and anesthesia-alone sham in a counterbalanced order separated by a recovery period. Both ECS and MST were given bilaterally at 2.5 x seizure threshold. Neurophysiological characteristics were derived from two scalp EEG electrode recording sites during and immediately following the ictal period, and were compared to sham treatment. EEG power within four frequencies (delta, theta, alpha and beta) was calculated. Our results support earlier findings from intracerebral electrode recordings demonstrating that MST- and ECS- induced seizures elicit differential patterns of EEG activation. Specifically, we found that ECS shows significantly more marked ictal expression, and more intense post-ictal suppression than MST in the theta, alpha, and beta frequency bands (Ps < .05). However, the ECS and MST were indistinguishable in the delta frequency band during both ictal and post-ictal periods. These results demonstrate that magnetic seizure induction can result in seizures that differ in some neurophysiological respects compared with ECS, but that these modalities share some aspects of seizure expression. The clinical significance of these similarities and differences awaits clinical correlation.

Survival of the probiotic Escherichia coli Nissle 1917 (EcN) in the gastrointestinal tract given in combination with oral mesalamine to healthy volunteers.

PubMed

Joeres-Nguyen-Xuan, Thai Hoa; Boehm, Stephan Karl; Joeres, Lars; Schulze, Juergen; Kruis, Wolfgang

2010-02-01

Mesalamine and the probiotic E. coli Nissle 1917 (EcN) are both effective agents for the treatment of ulcerative colitis. A combined therapy may have more than additive efficacy. However, mesalamine may have antimicrobial effects on EcN. In this prospective, randomized, double-blind, placebo-controlled study, 48 healthy volunteers took EcN in a run-in phase for 17 days (5-50 x 10(9) viable bacteria od). If stool samples became positive for EcN, volunteers received combination treatment with EcN plus either mesalamine (1500 mg twice a day) or placebo for 1 week. Fecal samples were further tested for EcN in 2- to 3-day intervals until a maximum of 48 weeks after treatment. Patient diaries, blood, and urine were checked to assess safety, compliance, and tolerance. During run-in, viable EcN were detected in 45 of the 48 volunteers (94%); 2 volunteers were positive before taking EcN. From days 1 to 7 of combination treatment (n = 40), the number of EcN-positive volunteers varied between 70% and 80% in the mesalamine group and between 85% and 95% in the placebo group. Differences between the groups were not significant (normal approximation: day 3, P > 0.15; day 5, P > 0.25; day 7, P > 0.076). At treatment discontinuation, 16 of 20 volunteers in the mesalamine group and 15 of 20 volunteers in the placebo group were EcN positive, whereas this figure dropped continuously up to week 12 after discontinuation (mesalamine, 7 of 20; placebo, 4 of 20). No differences between the groups were seen with regard to tolerance and safety. The combination of EcN and mesalamine has no significant effect on the survival of EcN in healthy volunteers.

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

NASA Astrophysics Data System (ADS)

Zhang, P.; Xu, X.; Shuai, P.; Chen, R. J.; Yan, X. L.; Zhang, Y. H.; Wang, M.; Litvinov, Yu. A.; Blaum, K.; Xu, H. S.; Bao, T.; Chen, X. C.; Chen, H.; Fu, C. Y.; He, J. J.; Kubono, S.; Lam, Y. H.; Liu, D. W.; Mao, R. S.; Ma, X. W.; Sun, M. Z.; Tu, X. L.; Xing, Y. M.; Yang, J. C.; Yuan, Y. J.; Zeng, Q.; Zhou, X.; Zhou, X. H.; Zhan, W. L.; Litvinov, S.; Audi, G.; Uesaka, T.; Yamaguchi, Y.; Yamaguchi, T.; Ozawa, A.; Sun, B. H.; Sun, Y.; Xu, F. R.

2017-04-01

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 QEC (46Cr) = 7604 (11) keV, QEC (50Fe) = 8150 (6) keV and QEC (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 (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.

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.

Molecular characterization of EcCIPK24 gene of finger millet (Eleusine coracana) for investigating its regulatory role in calcium transport.

PubMed

Chinchole, Mahadev; Pathak, Rajesh Kumar; Singh, Uma M; Kumar, Anil

2017-08-01

Finger millet grains contain exceptionally high levels of calcium which is much higher compared to other cereals and millets. Since calcium is an important macronutrient in human diet, it is necessary to explore the molecular basis of calcium accumulation in the seeds of finger millet. CIPK is a calcium sensor gene, having role in activating Ca 2+ exchanger protein by interaction with CBL proteins. To know the role of EcCIPK24 gene in seed Ca 2+ accumulation, sequence is retrieved from the transcriptome data of two finger millet genotypes GP1 (low Ca 2+ ) and GP45 (high Ca 2+ ), and the expression was determined through qRT-PCR. The higher expression was found in root, shoot, leaf and developing spike tissue of GP45 compared to GP1; structural analysis showed difference of nine SNPs and one extra beta sheet domain as well as differences in vacuolar localization was predicted; besides, the variation in amino acid composition among both the genotypes was also investigated. Molecular modeling and docking studies revealed that both EcCBL4 and EcCBL10 showed strong binding affinity with EcCIPK24 (GP1) compared to EcCIPK24 (GP45). It indicates a genotypic structural variation, which not only affects the affinity but also calcium transport efficiency after interaction of CIPK-CBL with calcium exchanger ( Ec CAX1b) to pull calcium in the vacuole. Based on the expression and in silico study, it can be suggested that by activating EcCAX1b protein, EcCIPK24 plays an important role in high seed Ca 2+ accumulation.

EcAMSat Video News File

NASA Image and Video Library

2017-11-03

A video news file (or a collection of raw video and interview clips) about the EcAMSat mission. Ever wonder what would happen if you got sick in space? NASA is sending samples of bacteria into low-Earth orbit to find out. One of the latest small satellite missions from NASA’s Ames Research Center in California’s Silicon Valley is the E. coli Anti-Microbial Satellite, or EcAMSat for short. The CubeSat – a spacecraft the size of a shoebox built from cube-shaped units – will explore how effectively antibiotics can combat E. coli bacteria in the low gravity of space. This information will help us improve how we fight infections, providing safer journeys for astronauts on their future voyages, and offer benefits for medicine here on Earth.

Effects of polyamine biosynthesis inhibitors on S-adenosylmethionine synthetase and S-adenosylmethionine decarboxylase activities in carrot cell cultures

Treesearch

S.C. Minocha; R. Minocha; A. Komamine

1991-01-01

Changes in the activites of S-adcnosylmethionine (SAM) synthetase (methionine adenosyltransferase, EC 2.5.1.6.) and SAM decarboxylase (EC 4.1.1.50) were studied in carrot (Daucus carota) cell cultures in response to 2,4-dichlorophenoxyacetic acid (2,4-D) and several inhibitors of polyamine biosynthesis. Activity of SAM synthetase increased...

Measuring Eating Competence: Psychometric Properties and Validity of the ecSatter Inventory

ERIC Educational Resources Information Center

Lohse, Barbara; Satter, Ellyn; Horacek, Tanya; Gebreselassie, Tesfayi; Oakland, Mary Jane

2007-01-01

Objective: Assess validity of the ecSatter Inventory (ecSI) to measure eating competence (EC). Design: Concurrent administration of ecSI with validated measures of eating behaviors using on-line and paper-pencil formats. Setting: The on-line survey was completed by 370 participants; 462 completed the paper version. Participants: Participants…

MIV-150 and zinc acetate combination provides potent and broad activity against HIV-1.

PubMed

Mizenina, Olga; Hsu, Mayla; Jean-Pierre, Ninochka; Aravantinou, Meropi; Levendosky, Keith; Paglini, Gabriela; Zydowsky, Thomas M; Robbiani, Melissa; Fernández-Romero, José A

2017-12-01

We previously showed that the combination of the non-nucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 with zinc acetate (ZA) formulated in a carrageenan (CG; MZC) gel provided macaques significant protection against vaginal simian-human immunodeficiency virus-RT (SHIV-RT) challenge, better than either MIV-150/CG or ZA/CG. The MZC gel was shown to be safe in a phase 1 clinical trial. Herein, we used in vitro approaches to study the antiviral properties of ZA and the MIV-150/ZA combination, compared to other NNRTIs. Like other NNRTIs, MIV-150 has EC 50 values in the subnanomolar to nanomolar range against wild type and NNRTI or RT-resistant HIVs. While less potent than NNRTIs, ZA was shown to be active in primary cells against laboratory-adapted and primary HIV-1 isolates and HIV-1 isolates/clones with NNRTI and RT resistance mutations, with EC 50 values between 20 and 110 μM. The MIV-150/ZA combination had a potent and broad antiviral activity in primary cells. In vitro resistance selection studies revealed that previously described NNRTI-resistant mutations were selected by MIV-150. ZA-resistant virus retained susceptibility to MIV-150 (and other RTIs) and MIV-150-selected virus remained sensitive to ZA. Notably, resistant virus was not selected when cultured in the presence of both ZA and MIV-150. This underscores the potency and breadth of the MIV-150/ZA combination, supporting preclinical macaque studies and the advancement of MZC microbicides into clinical testing.

Toward precise Q{sub EC} values for the superallowed 0{sup +}->0{sup +} beta decays of T=2 nuclides: The masses of {sup 20}Na, {sup 24}Al, {sup 28}P, and {sup 32}Cl

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

Wrede, C.; Wright Nuclear Structure Laboratory, Yale University, New Haven, Connecticut 06520; Clark, J. A.

High-precision measurements of superallowed 0{sup +}->0{sup +} beta decays of T=2 nuclides such as {sup 20}Mg, {sup 24}Si, {sup 28}S, and {sup 32}Ar can contribute to searches for physics beyond the standard model of particle physics if the Q{sub EC} values are accurate to a few keV or better. As a step toward providing precise Q{sub EC} values for these decays, the ground-state masses of the respective daughter nuclei {sup 20}Na, {sup 24}Al, {sup 28}P, and {sup 32}Cl have been determined by measuring the ({sup 3}He,t) reactions leading to them with the {sup 36}Ar({sup 3}He,t){sup 36}K reaction as a calibration.more » A quadrupole-dipole-dipole-dipole (Q3D) magnetic spectrograph was used together with thin ion-implanted carbon-foil targets of {sup 20}Ne, {sup 24}Mg, {sup 28}Si, {sup 32}S, and {sup 36}Ar. The masses of {sup 20}Na and {sup 32}Cl are found to be in good agreement with the values from the 2003 Atomic Mass Evaluation (AME03) [G. Audi, A. H. Wapstra, and C. Thibault, Nucl. Phys. A 729, 337 (2003)], and the precision has been improved by a factor of 6 in both cases. The masses of {sup 24}Al and {sup 28}P are found to be higher than the values from AME03 by 9.5 keV (3.2sigma) and 11.5 keV (3.6sigma), respectively, and the precision has been improved by a factor of 2.5 in both cases. The new {sup 32}Cl mass is used together with the excitation energy of its lowest T=2 level and the mass of {sup 32}Ar to derive an improved superallowed Q{sub EC} value of 6087.3(22) keV for this case. The effects on quantities related to standard-model tests including the beta-nu correlation coefficient a and the isospin-symmetry-breaking correction delta{sub C} are examined for the A=32 case.« less

Antioxidative activities of 62 wild mushrooms from Nepal and the phenolic profile of some selected species.

PubMed

Tamrakar, Sonam; Tran, Hai Bang; Nishida, Marina; Kaifuchi, Satoru; Suhara, Hiroto; Doi, Katsumi; Fukami, Katsuya; Parajuli, Gopal Prasad; Shimizu, Kuniyoshi

2016-10-01

Mushrooms have garnered immense popularity for their nutritional as well as medicinal values. The therapeutic potential of mushrooms in Nepal, a country well known for its biodiversity and natural medicinal resources, remains largely unstudied. Therefore, this study attempts to unveil the antioxidative properties of Nepalese wild mushrooms. Sixty-two wild mushroom samples were collected from several forests in different parts of Nepal. Ethanol and water extracts of the dried samples were tested for their antioxidative activities using total phenolic content (TPC), oxygen radical absorbance capacity (ORAC) assay, 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and reducing power (RP) assays. Ethanol extracts of samples belonging to the order Hymenochaetales showed significantly high activity in all the assays. Inonotus clemensiae had an exceptionally high TPC of 643.2 mg gallic acid equivalent (GAE)/g extract and also exhibited the lowest EC50 values in DPPH (0.081 mg/mL), ABTS (0.409 mg/mL), and EC0.5 value in reducing power (RP; 0.031 mg/mL) assays. High-performance liquid chromatography (HPLC) analysis of the top ten samples with the highest TPC was done to identify the phenolic compounds in the extracts, followed by liquid chromatography-mass spectrometry (LC-MS) analysis for some unknown compounds. These findings highlight the very strong antioxidative activity of Nepalese mushrooms, and paves the way for further research to explore their economic potential.

Evaluation and source attribution of freshwater contributions to Kinvarra Bay, Ireland, using (222)Rn, EC and stable isotopes as natural indicators.

PubMed

Schubert, Michael; Knoeller, Kay; Rocha, Carlos; Einsiedl, Florian

2015-03-01

Freshwater discharge into the coastal sea is of general interest for two reasons: (i) It acts as vehicle for the transport of contaminants or nutrients into the ocean, and (ii) it indicates the loss of significant volumes of freshwater that might be needed for irrigation or drinking water supply. Due to the large-scale and long-term nature of the related hydrological processes, locating and quantitatively assessing freshwater discharge into the sea require naturally occurring tracers that allow fast, inexpensive and straightforward detection. In several studies, the standard water parameters electrical conductivity (EC) and pH have proven their suitability in this regard. However, while distribution patterns of EC and pH in the coastal sea indicate freshwater discharge in general, a separation between discharging surface water and submarine groundwater discharge (SGD) is not possible with these alone. The naturally occurring radionuclide radon-222 has been shown to be useful in the quantification of SGD and its distinction from surface runoff. This study aimed to evaluate and compare the informative value of the three parameters-EC, pH and radon concentration-in detecting and quantifying SGD by carrying out a case study in a bay located in western Ireland. The results reveal that radon activity is the most sensitive parameter for detecting SGD. However, only the combined evaluation of radon, EC and pH allows a quantitative allocation of groundwater and surface water contributions to the overall freshwater discharge into the sea. This conclusion is independently supported by stable isotope data measured on selected samples.

Fine carbonaceous aerosol characteristics at a megacity during the Chinese Spring Festival as given by OC/EC online measurements

NASA Astrophysics Data System (ADS)

Liu, Baoshuang; Bi, Xiaohui; Feng, Yinchang; Dai, Qili; Xiao, Zhimei; Li, Liwei; Wu, Jianhui; Yuan, Jie; Zhang, YuFen

2016-11-01

The OC/EC online monitoring campaign was carried out in Tianjin of China from 8th February to 15th March 2015 during the Chinese Spring Festival period (CSFP). The concentrations of OC, EC, BC and other ambient pollutants (e.g. SO2, NO2 and PM2.5, etc.) in high time resolution were measured with related online-monitoring instruments. During the CSFP, according to the peaks of PM2.5 concentrations and number concentrations (NC) of aerosol particles with aerodynamic diameters between 0.3 and 2.5 μm, five pollution-events were generally identified and displayed. These pollution-events were closely associated with large-scale fireworks displaying, combustion activities such as heating for winter, and the stable meteorological conditions, etc. During the CSFP, EC and OC concentrations showed variations up to one order of magnitude. The uncertainty of instrument itself and the difference for measured methods, further caused the differences between thermal OC (measured OC by thermal method) and optical OC (measured OC by optical method) concentrations, as well as between thermal EC (measured EC by thermal method) and optical EC (measured EC by optical method) concentrations. The high-concentration carbonaceous aerosols could enlarge the uncertainty of measuring instrument, reducing the correlations between OC and EC, and enhance the differences among thermal EC, optical BC and optical EC. The OC/EC ratios and the percentages of SOC/OC would be declined, when the pollution-events formed during the CSFP. Due to the different sources for thermal POC and thermal SOC, the correlation of the two was relatively lower (R2 = 0.39). Thermal POC dominated over thermal OC during the CSFP.

Regulation (EC) No 1901/2006 on medicinal products for paediatric use & clinical research in vulnerable populations.

PubMed

Lehmann, Birka

2008-12-08

Before any medicinal product is authorised for use in adults, it must undergo extensive pharmaceutical consistency and stability tests, toxicological tests and clinical trials to ensure that it is of high quality, safe and effective.The same approach may not always be applied to medicinal products used to treat children.Studies showed that over 50% of the medicinal products used in children may not have been tested for use in this age group. The absence of suitable authorised medicinal products to treat conditions in children results from the fact that pharmaceutical companies do not adapt medicinal products to the needs of the paediatric population. This leaves health care professionals with no alternative other than to use medicinal products "off-label" and to use unauthorised products with the associated risks of inefficacy and/or adverse reactions.The Regulation (EC) No 1901/2006 sets up a system of requirements, rewards and incentives, together with horizontal measures, to ensure that medicinal products are researched, developed and authorised to meet the therapeutic needs of children.The Regulation is addressed to: 1. The pharmaceutical industry by setting out the legal framework for receiving rewards and incentives by conducting clinical trials in the paediatric population. 2. The Member States to set out to support research into, and the development and availability of, medicinal products for paediatric use. 3. The Community as funds for research into medicinal products for the paediatric population shall be provided for in the Community budget in order to support studies relating to medicinal products or active substances not covered by a patent or a supplementary protection certificate. The legal framework for conducting clinical trials, including children/minors, is set up in Directive 2001/20/EC, the Clinical Trials Directive (CTD), for the European Union (EU). The CTD establishes specific provisions regarding conduct of clinical trials, including multi

Distinct Spatiotemporal Activation Patterns of the Perirhinal-Entorhinal Network in Response to Cortical and Amygdala Input

PubMed Central

Willems, Janske G. P.; Wadman, Wytse J.; Cappaert, Natalie L. M.

2016-01-01

The perirhinal (PER) and entorhinal cortex (EC) receive input from the agranular insular cortex (AiP) and the subcortical lateral amygdala (LA) and the main output area is the hippocampus. Information transfer through the PER/EC network however, is not always guaranteed. It is hypothesized that this network actively regulates the (sub)cortical activity transfer to the hippocampal network and that the inhibitory system is involved in this function. This study determined the recruitment by the AiP and LA afferents in PER/EC network with the use of voltage sensitive dye (VSD) imaging in horizontal mouse brain slices. Electrical stimulation (500 μA) of the AiP induced activity that gradually propagated predominantly in the rostro-caudal direction: from the PER to the lateral EC (LEC). In the presence of 1 μM of the competitive γ-aminobutyric acid (GABAA) receptor antagonist bicuculline, AiP stimulation recruited the medial EC (MEC) as well. In contrast, LA stimulation (500 μA) only induced activity in the deep layers of the PER. In the presence of bicuculline, the initial population activity in the PER propagated further towards the superficial layers and the EC after a delay. The latency of evoked responses decreased with increasing stimulus intensities (50–500 μA) for both the AiP and LA stimuli. The stimulation threshold for evoking responses in the PER/EC network was higher for the LA than for the AiP. This study showed that the extent of the PER/EC network activation depends on release of inhibition. When GABAA dependent inhibition is reduced, both the AiP and the LA activate spatially overlapping regions, although in a distinct spatiotemporal fashion. It is therefore hypothesized that the inhibitory network regulates excitatory activity from both cortical and subcortical areas that has to be transmitted through the PER/EC network. PMID:27378860

Immunization with a novel Clostridium perfringens epsilon toxin mutant rETX(Y196E)-C confers strong protection in mice.

PubMed

Yao, Wenwu; Kang, Jingjing; Kang, Lin; Gao, Shan; Yang, Hao; Ji, Bin; Li, Ping; Liu, Jing; Xin, Wenwen; Wang, Jinglin

2016-04-06

Epsilon toxin (ETX) is produced by toxinotypes B and D of Clostridium perfringens. It can induce lethal enterotoxemia in domestic animals, mainly in sheep, goats and cattle, causing serious economic losses to global animal husbandry. In this study, a novel and stable epsilon toxin mutant rETX(Y196E)-C, obtained by substituting the 196th tyrosine (Y196) with glutamic acid (E) and introducing of 23 amino acids long C-terminal peptide, was determined as a promising recombinant vaccine candidate against enterotoxemia. After the third vaccination, the antibody titers against recombinant wild type (rETX) could reach 1:10(5) in each immunized group, and the mice were completely protected from 100 × LD50 (50% lethal dose) of rETX challenge. The mice in 15 μg subcutaneously immunized group fully survived at the dose of 500 × LD50 of rETX challenge and 80% of mice survived at 180 μg (1000 × LD50) of rETX administration. In vitro, immune sera from 15 μg subcutaneously immunized group could completely protect MDCK cells from 16 × CT50 (50% lethal dose of cells) of rETX challenge and protect against 10 × LD50 dose (1.8 μg) of rETX challenge in mice. These data suggest that recombinant protein rETX(Y196E)-C is a potential vaccine candidate for future applied researches.

77 FR 59702 - Promoting U.S. EC Regulatory Compatibility

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-28

... TRADE REPRESENTATIVE Promoting U.S. EC Regulatory Compatibility AGENCY: Office of the United... and European Commission (EC) share the goal of reducing excessive regulatory costs, unjustified..., safety, welfare, and the environment. Promoting this goal will help businesses to grow, create jobs, and...

In Vitro Evaluation of Antioxidant and Antimicrobial Activities of Melaleuca alternifolia Essential Oil

PubMed Central

Zhang, Xiaofeng; Guo, Yanjun; Guo, Liying; Jiang, Hui

2018-01-01

The in vitro antioxidant and antimicrobial activity of the essential oil from Melaleuca alternifolia (M. alternifolia) was evaluated in this report. The antioxidant potential of the essential oil from M. alternifolia was evaluated by the DPPH (2,2-diphenyl-1-picrylhydrazyl) method, thiobarbituric acid reactive species (TBARS) assay, and the hydroxyl radical scavenging activity method. The essential oil from M. alternifolia was able to reduce DPPH with an EC50 (concentration for 50% of maximal effect) of 48.35 μg/ml, inhibit the lipid peroxidation with an IC50 (50% inhibitory concentration) of 135.9 μg/ml, and eliminate hydroxyl radicals with an EC50 of 43.71 μg/ml. Antimicrobial screening, minimum inhibitory concentration, and minimum bactericidal concentration assays showed that the essential oil from M. alternifolia inhibited strongly the growth of different types of microorganisms, including Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Penicillium italicum Wehmer, and Penicillium digitatum Sacc. Thus, the essential oil of M. alternifolia possesses antioxidant and antimicrobial activity and could be suitable for use as a natural preservative ingredient in food, agriculture, and pharmaceutical industries. PMID:29854733

EMCS EC Connector Inspection Imagery

NASA Image and Video Library

2018-02-02

iss054e026863 (Feb. 2, 2018) --- The Plant Gravity Perception experiment in a centrifuge before its second run on the European Modular Cultivation System (EMCS) Experiment Container (EC) to test the gravity-sensing ability of plants in microgravity.

Increased numbers of circulating ECs are associated with systemic GVHD.

PubMed

Yan, Z; Zeng, L; Jia, L; Xu, S; Ding, S

2011-10-01

Circulating endothelial cells (ECs) are known to reflect endothelial injury, and endothelial injury is associated with graft-versus-host disease (GVHD). We hypothesised that circulating ECs might be associated with systemic acute graft-versus-host disease (aGVHD). BALB/c (H-2k(d) ) mice were treated with total body irradiation and then infused with C57B/6-derived T-cell-depleted bone marrow (TCD-BM) cells or TCD-BM cells and splenocytes. Cyclosporine was used to prevent aGVHD. Circulating ECs and allogeneic lymphocytes were analysed by flow cytometry at multiple time points. The morphology and ultrastructure of the endothelium were examined by light microscopy or transmission electron microscopy. The results indicated that the number of circulating ECs peaked at day 5 after lethal irradiation in all mice; allogenic transplanted mice (TCD-BM cells and splenocytes) developed typical aGVHD beginning at day 7, exhibiting both histological and clinical symptoms of disease. Circulating ECs peaked a second time at day 9 with aGVHD progression. However, following the administration of CSA, an absence of or a reduction in the amount of subsequent endothelial injury was observed. Circulating ECs might be associated with systemic aGVHD. © 2011 Blackwell Publishing Ltd.

Value of eddy-covariance data for individual-based, forest gap models

NASA Astrophysics Data System (ADS)

Roedig, Edna; Cuntz, Matthias; Huth, Andreas

2014-05-01

Individual-based forest gap models simulate tree growth and carbon fluxes on large time scales. They are a well established tool to predict forest dynamics and successions. However, the effect of climatic variables on processes of such individual-based models is uncertain (e.g. the effect of temperature or soil moisture on the gross primary production (GPP)). Commonly, functional relationships and parameter values that describe the effect of climate variables on the model processes are gathered from various vegetation models of different spatial scales. Though, their accuracies and parameter values have not been validated for the specific model scales of individual-based forest gap models. In this study, we address this uncertainty by linking Eddy-covariance (EC) data and a forest gap model. The forest gap model FORMIND is applied on the Norwegian spruce monoculture forest at Wetzstein in Thuringia, Germany for the years 2003-2008. The original parameterizations of climatic functions are adapted according to the EC-data. The time step of the model is reduced to one day in order to adapt to the high resolution EC-data. The FORMIND model uses functional relationships on an individual level, whereas the EC-method measures eco-physiological responses at the ecosystem level. However, we assume that in homogeneous stands as in our study, functional relationships for both methods are comparable. The model is then validated at the spruce forest Waldstein, Germany. Results show that the functional relationships used in the model, are similar to those observed with the EC-method. The temperature reduction curve is well reflected in the EC-data, though parameter values differ from the originally expected values. For example at the freezing point, the observed GPP is 30% higher than predicted by the forest gap model. The response of observed GPP to soil moisture shows that the permanent wilting point is 7 vol-% lower than the value derived from the literature. The light

Selective effect of myclobutanil enantiomers on fungicidal activity and fumonisin production by Fusarium verticillioides under different environmental conditions.

PubMed

Li, Na; Deng, Luqing; Li, Jianfang; Wang, Zhengbing; Han, Yiye; Liu, Chenglan

2018-05-01

Myclobutanil is a widely used triazole fungicide, comprising two enantiomers with different fungicidal activities, non-target toxicities, and environmental fates. The enantioselective effects of myclobutanil on fumonisin B (FB) production by Fusarium verticillioides, an important pathogen, have not yet been investigated. In the present study, the fungicidal activities of rac-myclobutanil and its enantiomers on F. verticillioides cultured on maize-based media were studied under different water activity and temperature conditions. The FB levels were measured to assess the enantioselective effects on FB production when F. verticillioides were cultured treated with EC 50 and EC 90 concentrations (concentrations inhibiting mycelial growth by 50.0% and 90.0%, respectively) of myclobutanil and enantiomers under different conditions. The fungicidal activities of rac-myclobutanil and its enantiomers decreased with increasing temperature and decreasing water activity. Little difference in fungicidal activity was observed between the enantiomers. FB production was significantly influenced by temperature, a w , and fungicides dose. At EC50 concentrations, rac-myclobutantil and its enantiomers were shown to enhance mycotoxin production and enantioselective effects of enantiomers on FB production were observed under certain conditions. This is the first report on the differential effects of myclobutanil enantiomers on the control of F. verticillioides growth and FB production in maize-based media under different conditions. Copyright © 2018 Elsevier Inc. All rights reserved.

Comparative analysis of antioxidant and antiproliferative activities of Rhodomyrtus tomentosa extracts prepared with various solvents.

PubMed

Abd Hamid, Hazrulrizawati; Mutazah, Roziasyahira; Yusoff, Mashitah M; Abd Karim, Nurul Ashikin; Abdull Razis, Ahmad Faizal

2017-10-01

Rhodomyrtus tomentosa (Aiton) Hassk. has a wide spectrum of pharmacological effects and has been used to treat wounds, colic diarrhoea, heartburns, abscesses and gynaecopathy. The potential antiproliferative activities of R. tomentosa extracts from different solvents were evaluated in vitro on HepG2, MCF-7 and HT 29 cell lines while antioxidant activity was monitored by radical scavenging assay (DPPH), copper reducing antioxidant capacity (CUPRAC) and β-carotene bleaching assay. Extracts from R. tomentosa show the viability of the cells in concentration-dependent manner. According to the IC50 obtained, the ethyl acetate extracts showed significant antiproliferative activity on HepG2 (IC50 11.47 ± 0.280 μg/mL), MCF-7 (IC50 2.68 ± 0.529 μg/mL) and HT 29 (IC50 16.18 ± 0.538 μg/mL) after 72 h of treatment. Bioassay guided fractionation of the ethyl acetate extract led to the isolation of lupeol. Methanol extracts show significant antioxidant activities in DPPH (EC50 110.25 ± 0.005 μg/ml), CUPRAC (EC50 53.84 ± 0.004) and β-carotene bleaching (EC50 58.62 ± 0.001) due to the presence of high total flavonoid and total phenolic content which were 110.822 ± 0.017 mg butylated hydroxytoluene (BHT)/g and 190.467 ± 0.009 mg gallic acid (GAE)/g respectively. Taken together, the results extracts show the R. tomentosa as a potential source of antioxidant and antiproliferative efficacy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Serotonin-producing enterochromaffin (EC) cells of gastrointestinal mucosa in dexamethasone-treated rats.

PubMed

Glisić, Radmila; Koko, Vesna; Todorović, Vera; Drndarević, Neda; Cvijić, Gordana

2006-09-11

The aim of our study was to investigate the morphological, immunohistochemical and ultrastructural changes of rat serotonin-producing enterochromaffin (EC) cells of gastrointestinal mucosa in dexamethasone-treated rats (D). After 12-daily intraperitoneal administration of 2 mg/kg dexamethasone, rats developed diabetes similar to human diabetes type 2. Stomach, small and large intestines were examined. Large serotonin positive EC cells appeared in the corpus mucosa epithelium of D group of rats, although these cells were not present in control (C) rats. Both volume fraction and the number of EC cells per mm(2) of mucosa were significantly increased only in the duodenum. However, the number of EC cells per circular sections of both antrum and small intestine was increased, but reduced both in the ascending and descending colon in D group. The dexamethasone treatment caused a strong reduction in number of granules in the antral EC cells, while it was gradually increased beginning from the jejunum to descending colon. The mean granular content was reduced in the antral EC cells but increased in the jejunal EC cells in D group. In conclusion, the present study showed that morphological changes in gut serotonin-producing EC cells occurred in diabetic rats.

Probing the interaction between cHAVc3 peptide and the EC1 domain of E-cadherin using NMR and molecular dynamics simulations.

PubMed

Alaofi, Ahmed; Farokhi, Elinaz; Prasasty, Vivitri D; Anbanandam, Asokan; Kuczera, Krzysztof; Siahaan, Teruna J

2017-01-01

The goal of this work is to probe the interaction between cyclic cHAVc3 peptide and the EC1 domain of human E-cadherin protein. Cyclic cHAVc3 peptide (cyclo(1,6)Ac-CSHAVC-NH 2 ) binds to the EC1 domain as shown by chemical shift perturbations in the 2D 1 H,- 15 N-HSQC NMR spectrum. The molecular dynamics (MD) simulations of the EC1 domain showed folding of the C-terminal tail region into the main head region of the EC1 domain. For cHAVc3 peptide, replica exchange molecular dynamics (REMD) simulations generated five structural clusters of cHAVc3 peptide. Representative structures of cHAVc3 and the EC1 structure from MD simulations were used in molecular docking experiments with NMR constraints to determine the binding site of the peptide on EC1. The results suggest that cHAVc3 binds to EC1 around residues Y36, S37, I38, I53, F77, S78, H79, and I94. The dissociation constants (K d values) of cHAVc3 peptide to EC1 were estimated using the NMR chemical shifts data and the estimated K d s are in the range of .5 × 10 -5 -7.0 × 10 -5  M.

50 CFR 640.24 - Authorized activities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Authorized activities. 640.24 Section 640.24 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE SPINY LOBSTER FISHERY OF THE GULF OF MEXICO AND SOUTH ATLANTIC Management...

50 CFR 640.24 - Authorized activities.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 10 2011-10-01 2011-10-01 false Authorized activities. 640.24 Section 640.24 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE SPINY LOBSTER FISHERY OF THE GULF OF MEXICO AND SOUTH ATLANTIC Management...

Development of an ex vivo lymph node explant model for identification of novel molecules active against Leishmania major.

PubMed

Peniche, Alex G; Osorio, Yaneth; Renslo, Adam R; Frantz, Doug E; Melby, Peter C; Travi, Bruno L

2014-01-01

Leishmaniasis is a vector-borne zoonotic infection affecting people in tropical and subtropical regions of the world. Current treatments for cutaneous leishmaniasis are difficult to administer, toxic, expensive, and limited in effectiveness and availability. Here we describe the development and application of a medium-throughput screening approach to identify new drug candidates for cutaneous leishmaniasis using an ex vivo lymph node explant culture (ELEC) derived from the draining lymph nodes of Leishmania major-infected mice. The ELEC supported intracellular amastigote proliferation and contained lymph node cell populations (and their secreted products) that enabled the testing of compounds within a system that mimicked the immunopathological environment of the infected host, which is known to profoundly influence parasite replication, killing, and drug efficacy. The activity of known antileishmanial drugs in the ELEC system was similar to the activity measured in peritoneal macrophages infected in vitro with L. major. Using the ELEC system, we screened a collection of 334 compounds, some of which we had demonstrated previously to be active against L. donovani, and identified 119 hits, 85% of which were confirmed to be active by determination of the 50% effective concentration (EC50). We found 24 compounds (7%) that had an in vitro therapeutic index (IVTI; 50% cytotoxic/effective concentration [CC50]/EC50) > 100; 19 of the compounds had an EC50 below 1 μM. According to PubChem searchs, 17 of those compounds had not previously been reported to be active against Leishmania. We expect that this novel method will help to accelerate discovery of new drug candidates for treatment of cutaneous leishmaniasis.

Development of an Ex Vivo Lymph Node Explant Model for Identification of Novel Molecules Active against Leishmania major

PubMed Central

Peniche, Alex G.; Osorio, Yaneth; Renslo, Adam R.; Frantz, Doug E.; Melby, Peter C.

2014-01-01

Leishmaniasis is a vector-borne zoonotic infection affecting people in tropical and subtropical regions of the world. Current treatments for cutaneous leishmaniasis are difficult to administer, toxic, expensive, and limited in effectiveness and availability. Here we describe the development and application of a medium-throughput screening approach to identify new drug candidates for cutaneous leishmaniasis using an ex vivo lymph node explant culture (ELEC) derived from the draining lymph nodes of Leishmania major-infected mice. The ELEC supported intracellular amastigote proliferation and contained lymph node cell populations (and their secreted products) that enabled the testing of compounds within a system that mimicked the immunopathological environment of the infected host, which is known to profoundly influence parasite replication, killing, and drug efficacy. The activity of known antileishmanial drugs in the ELEC system was similar to the activity measured in peritoneal macrophages infected in vitro with L. major. Using the ELEC system, we screened a collection of 334 compounds, some of which we had demonstrated previously to be active against L. donovani, and identified 119 hits, 85% of which were confirmed to be active by determination of the 50% effective concentration (EC50). We found 24 compounds (7%) that had an in vitro therapeutic index (IVTI; 50% cytotoxic/effective concentration [CC50]/EC50) > 100; 19 of the compounds had an EC50 below 1 μM. According to PubChem searchs, 17 of those compounds had not previously been reported to be active against Leishmania. We expect that this novel method will help to accelerate discovery of new drug candidates for treatment of cutaneous leishmaniasis. PMID:24126577

Antibacterial, antioxidant, and anticholinesterase activities of plant seed extracts from Brazilian semiarid region.

PubMed

Farias, Davi Felipe; Souza, Terezinha Maria; Viana, Martônio Ponte; Soares, Bruno Marques; Cunha, Arcelina Pacheco; Vasconcelos, Ilka Maria; Ricardo, Nágila Maria Pontes Silva; Ferreira, Paulo Michel Pinheiro; Melo, Vânia Maria Maciel; Carvalho, Ana Fontenele Urano

2013-01-01

The antimicrobial, antioxidant, and anticholinesterase activities of ethanolic seed extracts of twenty-one plant species from Brazilian semiarid region were investigated. The extracts were tested for antimicrobial activity against six bacteria strains and three yeasts. Six extracts presented activity against the Gram (-) organism Salmonella choleraesuis and the Gram (+) organisms Staphylococcus aureus and Bacillus subtilis. The MIC values ranged from 4.96 to 37.32 mg/mL. The Triplaris gardneriana extract presented activity against the three species, with MIC values 18.8, 13.76, and 11.15 mg/mL, respectively. Five extracts presented antioxidant activity, with EC50 values ranging from 69.73 μ g/mL (T. gardneriana) to 487.51 μ g/mL (Licania rigida). For the anticholinesterase activity, eleven extracts were capable of inhibiting the enzyme activity. From those, T. gardneriana, Parkia platycephala and Connarus detersus presented the best activities, with inhibition values of 76.7, 71.5, and 91.9%, respectively. The extracts that presented antimicrobial activity were tested for hemolytic assay against human A, B, and O blood types and rabbit blood. From those, only the Myracrodruon urundeuva extract presented activity (about 20% of hemolysis at the lowest tested concentration, 1.9 µg/mL). Infrared spectroscopy of six representative extracts attested the presence of tannins, polyphenols, and flavonoids, which was confirmed by a qualitative phytochemical assay.

In vitro anti-reovirus activity of kuraridin isolated from Sophora flavescens against viral replication and hemagglutination.

PubMed

Kwon, Hyung-Jun; Jeong, Jae-Ho; Lee, Seung Woong; Ryu, Young Bae; Jeong, Hyung Jae; Jung, Kyungsook; Lim, Jae Sung; Cho, Kyoung-Oh; Lee, Woo Song; Rho, Mun-Chual; Park, Su-Jin

2015-08-01

In this study, we evaluated the anti-reovirus activity of kuraridin isolated from the roots of Sophora flavescens. In particular, we focused on whether this property is attributable to direct inhibition of reovirus attachment and/or inhibition of viral replication with the aid of time-of-addition (pre-treatment, simultaneous treatment, and post-treatment) experiments. No significant antiviral activity of kuraridin was detected in the pre-treatment assay. In the simultaneous assay, the 50% effective inhibitory concentrations (EC50) of kuraridin were 15.3-176.9 μM against human type 1-3 reoviruses (HRV1-3) and Korean porcine reovirus (PRV). Kuraridin completely blocked binding of viral sigma 1 protein to sialic acids at concentrations lower than 82.5 μM in the hemagglutination inhibition assay. Moreover, kuraridin inhibited HRV1-3 and PRV viral replication with EC50 values of 14.0-62.0 μM. Quantitative real-time PCR analysis disclosed strong suppression of reovirus RNA synthesis at the late stage (18 h) of virus replication by kuraridin. The viral yields of kuraridin-treated cells were significantly reduced at 24 h post-infection, compared with DMSO-treated cells. Our results collectively suggest that kuraridin inhibits virus adsorption and replication by inhibiting hemagglutination, viral RNA and protein synthesis and virus shedding, supporting its utility as a viable candidate antiviral drug against reoviruses. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Measuring phosphatidic acid phosphatase (EC 3.1.3.4) activity using two phosphomolybdate-based colorimetric methods

USDA-ARS?s Scientific Manuscript database

Phosphatidate phosphatase (3-sn-phosphatidate phosphohydrolase, EC 3.1.3.4), which is also known as PAP, catalyzes the dephosphorylation of phosphatidate (PtdOH) to form diacylglycerol (DAG) and inorganic phosphate. In eukaryotes, PAP driven reaction is the committed step in the synthesis of triacyl...

Novel trans-Ferulic Acid Derivatives Containing a Chalcone Moiety as Potential Activator for Plant Resistance Induction.

PubMed

Gan, Xiuhai; Hu, Deyu; Wang, Yanjiao; Yu, Lu; Song, Baoan

2017-06-07

A series of novel trans-ferulic acid derivatives containing a chalcone moiety were designed and synthesized to induce plant resistance. Antiviral activities of the compounds were evaluated. Bioassay results demonstrated that compounds F3, F6, F17, and F27 showed remarkable curative, protective, and inactivating activities against tobacco mosaic virus (TMV). With a 50% effective concentration (EC 50 ) value of 98.78 μg mL -1 , compound F27 exhibited the best protective activity compared with trans-ferulic acid (328.6 μg mL -1 ), dufulin (385.6 μg mL -1 ), and ningnanmycin (241.3 μg mL -1 ). This protective ability was associated with potentiation of defense-related enzyme activity and activation of photosynthesis of tobacco at an early stage. This notion was confirmed by up-regulated expression of stress responses and photosynthesis regulating proteins. This work revealed that F27 can induce resistance and enhance plant tolerance to TMV infection. Hence, F27 can be considered as a novel activator for inducing plant resistance.

Synthesis, characterization and monoamine transporter activity of the new psychoactive substance mexedrone and its N-methoxy positional isomer, N-methoxymephedrone

PubMed Central

McLaughlin, Gavin; Morris, Noreen; Kavanagh, Pierce V.; Power, John D.; Dowling, Geraldine; Twamley, Brendan; O'Brien, John; Talbot, Brian; Walther, Donna; Partilla, John S.; Baumann, Michael H.; Brandt, Simon D.

2017-01-01

3-Methoxy-2-(methylamino)-1-(4-methylphenyl)propan-1-one (mexedrone) appeared in 2015 and was advertised by UK Internet retailers as a non-controlled mephedrone derivative (2-(methylamino)-1-(4-methylphenyl)propan-1-one), which was of particular interest to countries who operate generic drugs legislation. This study describes the synthesis and analytical characterization of mexedrone and the differentiation from its isomer, N-methoxymephedrone, which was predicted to be a suitable candidate before the identity of mexedrone was revealed. A full analytical characterization is described using various chromatographic, spectroscopic and mass spectrometric platforms and X-ray crystal structure analysis. The analytical data obtained for a vendor sample were consistent with the synthesized mexedrone reference standard and analytical differentiation between the mexedrone and N-methoxymephedrone positional isomers was achieved. Furthermore, α-chloromethylmephedrone was identified as a by-product during mexedrone synthesis. All three substances were also studied for their uptake and releasing properties at dopamine transporters (DAT), norepinephrine transporters (NET) and serotonin transporters (SERT) using in vitro monoamine transporter assays in rat brain synaptosomes and compared to mephedrone. Mexedrone was a weak non-selective uptake blocker with IC50 values in the low μM range. It was also devoid of releasing activity at DAT and NET but displayed weak releasing activity at SERT (EC50= 2.5 μM). The isomer N-methoxymephedrone was found to be a weak uptake blocker at DAT, NET and SERT, as well as a fully efficacious substrate-type releasing agent across all three transporters with EC50 values in the low micromolar range. The synthesis by-product α-chloromethylmephedrone was inactive in all assays. PMID:27524685

Pharmacological selectivity of the cloned human P2U-purinoceptor: potent activation by diadenosine tetraphosphate.

PubMed Central

Lazarowski, E. R.; Watt, W. C.; Stutts, M. J.; Boucher, R. C.; Harden, T. K.

1995-01-01

1. The human P2U-purinoceptor was stably expressed in 1321N1 human astrocytoma cells and the pharmacological selectivity of the expressed receptor was studied by measurement of inositol lipid hydrolysis. 2. High basal levels of inositol phosphates occurred in P2U-purinoceptor-expressing cells. This phenomenon was shown to be due to release of large amounts of ATP from 1321N1 cells, and could be circumvented by adoption of an assay protocol that did not involve medium changes. 3. UTP, ATP and ATP gamma S were full and potent agonists for activation of phospholipase C with EC50 values of 140 nM, 230 nM, and 1.72 microM, respectively. 5BrUTP, 2C1ATP and 8BrATP were also full agonists although less potent than their natural congeners. Little or no effect was observed with the selective P2Y-, P2X-, and P2T-purinoceptor agonists, 2MeSATP, alpha,beta-MeATP, and 2MeSADP, respectively. 4. Diadenosine tetraphosphate, Ap4A, was a surprisingly potent agonist at the expressed P2U-purinoceptor with an EC50 (720 nM) in the range of the most potent P2U-purinoceptor agonists. Ap4A may be a physiologically important activator of P2U-purinoceptors. PMID:8564228

Allosteric activation of the follicle-stimulating hormone (FSH) receptor by selective, nonpeptide agonists.

PubMed

Yanofsky, Stephen D; Shen, Emily S; Holden, Frank; Whitehorn, Erik; Aguilar, Barbara; Tate, Emily; Holmes, Christopher P; Scheuerman, Randall; MacLean, Derek; Wu, May M; Frail, Donald E; López, Francisco J; Winneker, Richard; Arey, Brian J; Barrett, Ronald W

2006-05-12

The pituitary glycoprotein hormones, luteinizing hormone and follicle-stimulating hormone (FSH), act through their cognate receptors to initiate a series of coordinated physiological events that results in germ cell maturation. Given the importance of FSH in regulating folliculogenesis and fertility, the development of FSH mimetics has been sought to treat infertility. Currently, purified and recombinant human FSH are the only FSH receptor (FSH-R) agonists available for infertility treatment. By screening unbiased combinatorial chemistry libraries, using a cAMP-responsive luciferase reporter assay, we discovered thiazolidinone agonists (EC50's = 20 microm) of the human FSH-R. Subsequent analog library screening and parallel synthesis optimization resulted in the identification of a potent agonist (EC50 = 2 nm) with full efficacy compared with FSH that was FSH-R-selective and -dependent. The compound mediated progesterone production in Y1 cells transfected with the human FSH-R (EC50 = 980 nm) and estradiol production from primary rat ovarian granulosa cells (EC50 = 10.5 nm). This and related compounds did not compete with FSH for binding to the FSH-R. Use of human FSH/thyroid-stimulating hormone (TSH) receptor chimeras suggested a novel mechanism for receptor activation through a binding site independent of the natural hormone binding site. This study is the first report of a high affinity small molecule agonist that activates a glycoprotein hormone receptor through an allosteric mechanism. The small molecule FSH receptor agonists described here could lead to an oral alternative to the current parenteral FSH treatments used clinically to induce ovarian stimulation for both in vivo and in vitro fertilization therapy.

50 CFR 80.50 - What activities are eligible for funding under the Pittman-Robertson Wildlife Restoration Act?

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 8 2011-10-01 2011-10-01 false What activities are eligible for funding under the Pittman-Robertson Wildlife Restoration Act? 80.50 Section 80.50 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE...

50 CFR 80.50 - What activities are eligible for funding under the Pittman-Robertson Wildlife Restoration Act?

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 9 2013-10-01 2013-10-01 false What activities are eligible for funding under the Pittman-Robertson Wildlife Restoration Act? 80.50 Section 80.50 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE...

50 CFR 80.50 - What activities are eligible for funding under the Pittman-Robertson Wildlife Restoration Act?

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 9 2014-10-01 2014-10-01 false What activities are eligible for funding under the Pittman-Robertson Wildlife Restoration Act? 80.50 Section 80.50 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE...

50 CFR 80.50 - What activities are eligible for funding under the Pittman-Robertson Wildlife Restoration Act?

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 9 2012-10-01 2012-10-01 false What activities are eligible for funding under the Pittman-Robertson Wildlife Restoration Act? 80.50 Section 80.50 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE...

Inter-comparison of NIOSH and IMPROVE protocols for OC and EC determination: implications for inter-protocol data conversion

NASA Astrophysics Data System (ADS)

Wu, Cheng; Huang, X. H. Hilda; Ng, Wai Man; Griffith, Stephen M.; Zhen Yu, Jian

2016-09-01

) yields the following equation: M1(urban data) : ECIMP_TOR = 2.20 × ECNSH_TOT - 0.05. While both M1 and M2 are acceptable, M2 with site-specific parameters provides the best reconstruction performance. Secondary OC (SOC) estimation using OC and EC by the two protocols is compared. An analysis of the usability of reconstructed ECIMP_TOR and OCIMP_TOR suggests that the reconstructed values are not suitable for SOC estimation due to the poor reconstruction of the OC / EC ratio.

Research on Intellectual Property Conflicts Identification in Knowledge Transferring among EC Enterprises

NASA Astrophysics Data System (ADS)

Su, Shibin

As the lacks of existing research about intellectual property conflicts management of EC enterprise, the paper analysis the intellectual property conflicts in knowledge transferring among EC enterprises by intellectual property types, then, the paper makes research on intellectual property conflicts identification in knowledge transferring among EC enterprises, and gives relative assumption, meanwhile, the paper makes quantities identification of intellectual property conflicts in knowledge transferring among EC enterprises by evidential theory, finally, the paper gives the further research orientations.

Antioxidant and antiangiogenic activities of the essential oils of Myristica fragrans and Morinda citrifolia.

PubMed

Piaru, Suthagar Pillai; Mahmud, Roziahanim; Abdul Majid, Amin Malik Shah; Mahmoud Nassar, Zeyad Daoud

2012-04-01

Toinvestigate the anti-angiogenic activity and antioxidant properties of Myristica fragrans (M. fragrans) (nutmeg) and Morinda citrifolia (M. citrifolia)(mengkudu) oils. The nutmeg and megkudu essential oils were obtained by steam distillation. The antioxidant activities of both essential oils were determined by beta-carotene/linoleic acid bleaching assay and reducing power while the anti-angiogenic activity was investigated using rat aortic ring assay using various concentrations. The results showed that nutmeg oil has higher antioxidant activity than mengkudu oil. The nutmeg oil effectively inhibited the oxidation of linoleic acid with (88.68±0.1)% while the inhibition percentage of oxidation of linoleic acid of the mengkudu oil is (69.44±0.4)%. The nutmeg oil and mengkudu oil showed reducing power with an EC(50) value of 181.4 μg/mL and 3 043.0 μg/mL, respectively. The antiangiogenic activity of nutmeg oil showed significant antiangiogenic activity with IC(50) of 77.64 μg/mL comparing to mengkudu oil which exhibits IC(50) of 109.30 μg/mL. Bioactive compound(s) will be isolated from the nutmeg essential oil to be developed as antiangiogenic drugs. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Chemical composition and anti-herpes simplex virus type 1 (HSV-1) activity of extracts from Cornus canadensis.

PubMed

Lavoie, Serge; Côté, Isabelle; Pichette, André; Gauthier, Charles; Ouellet, Michaël; Nagau-Lavoie, Francine; Mshvildadze, Vakhtang; Legault, Jean

2017-02-22

Many plants of boreal forest of Quebec have been used by Native Americans to treat a variety of microbial infections. However, the antiviral activities of these plants have been seldom evaluated on cellular models to validate their in vitro efficiencies. In this study, Cornus canadensis L. (Cornaceae), a plant used in Native American traditional medicine to treat possible antiviral infections, has been selected for further examination. The plant was extracted by decoction and infusion with water, water/ethanol 1:1 and ethanol to obtain extracts similar to those used by Native Americans. The effects of the extracts were tested on herpes simplex virus type-1 (HSV-1) using a plaque reduction assay. Moreover, bioassay-guided fractionation was achieved to isolate bioactive compounds. Water/ethanol 1:1 infusion of C. canadensis leaves were the most active extracts to inhibit virus absorption with EC 50 of about 9 μg mL -1 , whereas for direct mode, both extraction methods using water or water/ethanol 1:1 as solvent were relatively similar with EC 50 ranging from 11 to 17 μg mL -1 . The fractionation led to the identification of active fractions containing hydrolysable tannins. Tellimagrandin I was found the most active compound with an EC 50 of 2.6 μM for the direct mode and 5.0 μM for the absorption mode. Altogether, the results presented in this work support the antiviral activity of Cornus canadensis used in Native American traditional medicine.

Expression of an Acid Urease with Urethanase Activity in E. coli and Analysis of Urease Gene.

PubMed

Liu, Xiaofeng; Zhang, Qian; Zhou, Nandi; Tian, Yaping

2017-03-01

Urea in alcoholic beverage is a precursor of ethyl carbamate (EC), which is carcinogenic. Enzymatic elimination of urea has attracted much research interest. Acid urease with good tolerance toward ethanol and acid is ideal enzyme for such applications. In the present work, the structural genes of urease from Providencia rettgeri JN-B815, ureABC were efficiently expressed in E. coli BL21(DE3) in an active form (apourease) exhibiting both urease and urethanase (hydrolyze EC) activities. The specific activities of the purified apourease were comparatively low, which were 2.1 U/mg for urease and 0.6 U/mg for urethanase, respectively. However, apourease exhibited good resistance toward ethanol and acidic conditions. The relative activities of urease and urethanase remained over 80% in the buffers within pH 4-7. And the recoveries of both urease and urethanase activities were more than 50% in 5-25% ethanol solution. Apourease was utilized to eliminate urea in wine, and the residual urea in model wine was less than 50% after treatment with apourease for 30 h. Then 3D structure of UreC was predicted, and it was docked with urea and EC, respectively. The docking result revealed that three hydrogen bonds were formed between urea and amino acid residues in the active site of urease, whereas only one hydrogen bond can be formed between EC and the active center. Moreover, EC exhibited greater steric hindrance than urea when combined with the active site. Due to the low specific activities of apourease, both structural genes and accessory genes of urease were co-expressed in E. coli BL21(DE3). The holoenzyme was expressed as inclusion body. After renaturation and purification, the specific activities of urease and urethanase reached 10.7 and 3.8 U/mg, which were 5.62-fold and 6.33-fold of those of apourease, respectively. Therefore, accessory subunits of urease play an important role in enhancing urease and urethanase activities.

NASA FACTS: E. coli AntiMicrobial Satellite (EcAMSat)

NASA Technical Reports Server (NTRS)

Spremo, Stevan; Cappuccio, Gelsomina; Tomko, David

2013-01-01

The E. coli AntiMicrobial Satellite(EcAMSat) mission will investigate space microgravity affects on the antibiotic resistance of E. coli, a bacterial pathogen responsible for urinary tract infection in humans and animals. EcAMSat is being developed through a partnership between NASAs Ames Research Center and the Stanford University School of Medicine. Dr. A.C. Matin is the Stanford University Principal Investigator. EcAMSat will investigate spaceflight effects on bacterial antibiotic resistance and its genetic basis. Bacterial antibiotic resistance may pose a danger to astronauts in microgravity, where the immune response is weakened. Scientists believe that the results of this experiment could help design effective countermeasures to protect astronauts health during long duration human space missions.

Activated ovarian endothelial cells promote early follicular development and survival.

PubMed

Kedem, Alon; Aelion-Brauer, Anate; Guo, Peipei; Wen, Duancheng; Ding, Bi-Sen; Lis, Raphael; Cheng, Du; Sandler, Vladislav M; Rafii, Shahin; Rosenwaks, Zev

2017-09-19

New data suggests that endothelial cells (ECs) elaborate essential "angiocrine factors". The aim of this study is to investigate the role of activated ovarian endothelial cells in early in-vitro follicular development. Mouse ovarian ECs were isolated using magnetic cell sorting or by FACS and cultured in serum free media. After a constitutive activation of the Akt pathway was initiated, early follicles (50-150 um) were mechanically isolated from 8-day-old mice and co-cultured with these activated ovarian endothelial cells (AOEC) (n = 32), gel (n = 24) or within matrigel (n = 27) in serum free media for 14 days. Follicular growth, survival and function were assessed. After 6 passages, flow cytometry showed 93% of cells grown in serum-free culture were VE-cadherin positive, CD-31 positive and CD 45 negative, matching the known EC profile. Beginning on day 4 of culture, we observed significantly higher follicular and oocyte growth rates in follicles co-cultured with AOECs compared with follicles on gel or matrigel. After 14 days of culture, 73% of primary follicles and 83% of secondary follicles co-cultured with AOEC survived, whereas the majority of follicles cultured on gel or matrigel underwent atresia. This is the first report of successful isolation and culture of ovarian ECs. We suggest that co-culture with activated ovarian ECs promotes early follicular development and survival. This model is a novel platform for the in vitro maturation of early follicles and for the future exploration of endothelial-follicular communication. In vitro development of early follicles necessitates a complex interplay of growth factors and signals required for development. Endothelial cells (ECs) may elaborate essential "angiocrine factors" involved in organ regeneration. We demonstrate that co-culture with ovarian ECs enables culture of primary and early secondary mouse ovarian follicles.

Selective neurotensin-derived internally quenched fluorogenic substrates for neurolysin (EC 3.4.24.16): comparison with thimet oligopeptidase (EC 3.4.24.15) and neprilysin (EC 3.4.24.11).

PubMed

Oliveira, V; Campos, M; Hemerly, J P; Ferro, E S; Camargo, A C; Juliano, M A; Juliano, L

2001-05-15

Internally quenched fluorescent peptides derived from neurotensin (pELYENKPRRPYIL) sequence were synthesized and assayed as substrates for neurolysin (EC 3.4.24.16), thimet oligopeptidase (EC 3.4.24.15 or TOP), and neprilysin (EC 3.4.24.11 or NEP). Abz-LYENKPRRPYILQ-EDDnp (where EDDnp is N-(2,4-dinitrophenyl)ethylenediamine and Abz is ortho-aminobenzoic acid) was derived from neurotensin by the introduction of Q-EDDnp at the C-terminal end of peptide and by the substitution of the pyroglutamic (pE) residue at N-terminus for Abz and a series of shorter peptides was obtained by deletion of amino acids residues from C-terminal, N-terminal, or both sides. Neurolysin and TOP hydrolyzed the substrates at P--Y or Y--I or R--R bonds depending on the sequence and size of the peptides, while NEP cleaved P-Y or Y-I bonds according to its S'(1) specificity. One of these substrates, Abz-NKPRRPQ-EDDnp was a specific and sensitive substrate for neurolysin (k(cat) = 7.0 s(-1), K(m) = 1.19 microM and k(cat)/K(m) = 5882 mM(-1). s(-1)), while it was completely resistant to NEP and poorly hydrolyzed by TOP and also by prolyl oligopeptidase (EC 3.4.21.26). Neurolysin concentrations as low as 1 pM were detected using this substrate under our conditions and its analogue Abz-NKPRAPQ-EDDnp was hydrolyzed by neurolysin with k(cat) = 14.03 s(-1), K(m) = 0.82 microM, and k(cat)/K(m) = 17,110 mM(-1). s(-1), being the best substrate so far described for this peptidase. Copyright 2001 Academic Press.

Melicope ptelefolia leaf extracts exhibit antioxidant activity and exert anti-proliferative effect with apoptosis induction on four different cancer cell lines.

PubMed

Kabir, Mohammad Faujul; Mohd Ali, Johari; Abolmaesoomi, Mitra; Hashim, Onn Haji

2017-05-05

Melicope ptelefolia is a well-known herb in a number of Asian countries. It is often used as vegetable salad and traditional medicine to address various ailments. However, not many studies have been currently done to evaluate the medicinal benefits of M. ptelefolia (MP). The present study reports antioxidant, anti-proliferative, and apoptosis induction activities of MP leaf extracts. Young MP leaves were dried, powdered and extracted sequentially using hexane (HX), ethyl acetate (EA), methanol (MeOH) and water (W). Antioxidant activity was evaluated using ferric reducing antioxidant power (FRAP), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) radicals scavenging and cellular antioxidant activity (CAA) assays. Anti-proliferative activity was evaluated through cell viability assay, using the following four human cancer cell lines: breast (HCC1937, MDA-MB-231), colorectal (HCT116) and liver (HepG2). The anti-proliferative activity was further confirmed through cell cycle and apoptosis assays, including annexin-V/7-aminoactinomycin D staining and measurements of caspase enzymes activation and inhibition. Overall, MP-HX extract exhibited the highest antioxidant potential, with IC 50 values of 267.73 ± 5.58 and 327.40 ± 3.80 μg/mL for ABTS and DPPH radical-scavenging assays, respectively. MP-HX demonstrated the highest CAA activity in Hs27 cells, with EC 50 of 11.30 ± 0.68 μg/mL, while MP-EA showed EC 50 value of 37.32 ± 0.68 μg/mL. MP-HX and MP-EA showed promising anti-proliferative activity towards the four cancer cell lines, with IC 50 values that were mostly below 100 μg/mL. MP-HX showed the most notable anti-proliferative activity against MDA-MB-231 (IC 50  = 57.81 ± 3.49 μg/mL) and HCT116 (IC 50  = 58.04 ± 0.96 μg/mL) while MP-EA showed strongest anti-proliferative activity in HCT116 (IC 50  = 64.69 ± 0.72 μg/mL). The anticancer potential of MP-HX and MP-EA were also

Assignment of EC Numbers to Enzymatic Reactions with Reaction Difference Fingerprints

PubMed Central

Hu, Qian-Nan; Zhu, Hui; Li, Xiaobing; Zhang, Manman; Deng, Zhe; Yang, Xiaoyan; Deng, Zixin

2012-01-01

The EC numbers represent enzymes and enzyme genes (genomic information), but they are also utilized as identifiers of enzymatic reactions (chemical information). In the present work (ECAssigner), our newly proposed reaction difference fingerprints (RDF) are applied to assign EC numbers to enzymatic reactions. The fingerprints of reactant molecules minus the fingerprints of product molecules will generate reaction difference fingerprints, which are then used to calculate reaction Euclidean distance, a reaction similarity measurement, of two reactions. The EC number of the most similar training reaction will be assigned to an input reaction. For 5120 balanced enzymatic reactions, the RDF with a fingerprint length at 3 obtained at the sub-subclass, subclass, and main class level with cross-validation accuracies of 83.1%, 86.7%, and 92.6% respectively. Compared with three published methods, ECAssigner is the first fully automatic server for EC number assignment. The EC assignment system (ECAssigner) is freely available via: http://cadd.whu.edu.cn/ecassigner/. PMID:23285222

Taking back a little of what you have lost: the meaning of using an Environmental Control System (ECS) for people with high cervical spinal cord injury.

PubMed

Verdonck, Michele; Nolan, Maeve; Chard, Gill

2017-09-22

Assistive technologies have deep and personal meanings for people with disabilities. This study sought to provide an in-depth exploration of the subjective meaning of Environmental Control System (ECS) use for people with high cervical spinal cord injury. Interpretative Phenomenological Analysis (IPA) was used to explore the personal meaning of ECS. In-depth interviews with five participants were analyzed according to recommended IPA guidelines to produce a rich phenomenological account of lived experience. This study identified two overarching themes, one of which was the subject of an earlier publication. This paper focuses on the second theme "taking back a little of what you have lost" and its two main components "reclaiming a little doing" and "feeling enabled". Doing everyday things, being less dependent on others and feeling safer and less needy all contributed to participants experience of regaining something important of what had been lost. A nuanced range of meanings, demonstrating how "a little can mean a lot" emerged from this study. For those with high cervical spinal cord injury, "reclaiming a little doing" resulted in subtle, but subjectively significant, improvements in identity, relationships and well-being, while "feeling enabled" was both enjoyable and empowering and led to an increased sense of safety and reduced neediness. The potentially powerful impact on individuals with life-altering injuries of reclaiming a little of what they had lost, supports the value of more widespread access to and provision of ECS. Implications for rehabilitation While ECS use produces only a "little" objective change in activity levels, it subjectively means "a lot" to people with high level injuries. ECS enable people to "do" everyday things as well help in supporting them to "feel" less dependent and needy. Using ECS facilitates much more than functional tasks and a sense of security. It helps promote positive self-perception and continuity of being. It is

76 FR 75772 - Airworthiness Directives; Eurocopter France Model EC 120B Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-05

... Airworthiness Directives; Eurocopter France Model EC 120B Helicopters AGENCY: Federal Aviation Administration... the Eurocopter France Model EC 120B helicopters. This AD requires modifying the pilot cyclic control... include an AD that would apply to Eurocopter France Model EC 120B helicopters. That NPRM was published in...

Glucosidase inhibitory activity and antioxidant activity of flavonoid compound and triterpenoid compound from Agrimonia Pilosa Ledeb

PubMed Central

2014-01-01

Background In Chinese traditional medicine, Agrimonia pilosa Ledeb (APL) exhibits great effect on treatment of type 2 diabetes mellitus (T2DM), however its mechanism is still unknown. Considering that T2DM are correlated with postprandial hyperglycemia and oxidative stress, we investigated the α-glucosidase inhibitory activity and the antioxidant activity of flavonoid compound (FC) and triterpenoid compound (TC) from APL. Methods Entire plants of APL were extracted using 95% ethanol and 50% ethanol successively. The resulting extracts were partitioned and isolated by applying liquid chromatography using silica gel column and Sephadex LH 20 column to give FC and TC. The content of total flavonoids in FC and the content of total triterpenoids in TC were determined by using UV spectrophotometry. HPLC analysis was used to identify and quantify the monomeric compound in FC and TC. The α-glucosidase inhibitory activities were determined using the chromogenic method with p-nitrophenyl-α-D-glucopyranoside as substrate. Antioxidant activities were assessed through three kinds of radical scavenging assays (DPPH radical, ABTS radical and hydroxyl radical) & β-carotene-linoleic acid assay. Results The results indicate FC is abundant of quercitrin, and hyperoside, and TC is abundant of 1β, 2β, 3β, 19α-tetrahydroxy-12-en-28-oic acid (265.2 mg/g) and corosolic acid (100.9 mg/g). The FC & the TC have strong α-glucosidase inhibitory activities with IC50 of 8.72 μg/mL and 3.67 μg/mL, respectively. We find that FC show competitive inhibition against α-glucosidase, while the TC exhibits noncompetitive inhibition. Furthermore, The FC exhibits significant radical scavenging activity with the EC50 values of 7.73 μg/mL, 3.64 μg/mL and 5.90 μg/mL on DPPH radical, hydroxyl radical and ABTS radical, respectively. The FC also shows moderate anti-lipid peroxidation activity with the IC50 values of 41.77 μg/mL on inhibiting β-carotene bleaching. Conclusion These results

Glucosidase inhibitory activity and antioxidant activity of flavonoid compound and triterpenoid compound from Agrimonia Pilosa Ledeb.

PubMed

Liu, Xi; Zhu, Liancai; Tan, Jun; Zhou, Xuemei; Xiao, Ling; Yang, Xian; Wang, Bochu

2014-01-10

In Chinese traditional medicine, Agrimonia pilosa Ledeb (APL) exhibits great effect on treatment of type 2 diabetes mellitus (T2DM), however its mechanism is still unknown. Considering that T2DM are correlated with postprandial hyperglycemia and oxidative stress, we investigated the α-glucosidase inhibitory activity and the antioxidant activity of flavonoid compound (FC) and triterpenoid compound (TC) from APL. Entire plants of APL were extracted using 95% ethanol and 50% ethanol successively. The resulting extracts were partitioned and isolated by applying liquid chromatography using silica gel column and Sephadex LH 20 column to give FC and TC. The content of total flavonoids in FC and the content of total triterpenoids in TC were determined by using UV spectrophotometry. HPLC analysis was used to identify and quantify the monomeric compound in FC and TC. The α-glucosidase inhibitory activities were determined using the chromogenic method with p-nitrophenyl-α-D-glucopyranoside as substrate. Antioxidant activities were assessed through three kinds of radical scavenging assays (DPPH radical, ABTS radical and hydroxyl radical) & β-carotene-linoleic acid assay. The results indicate FC is abundant of quercitrin, and hyperoside, and TC is abundant of 1β, 2β, 3β, 19α-tetrahydroxy-12-en-28-oic acid (265.2 mg/g) and corosolic acid (100.9 mg/g). The FC & the TC have strong α-glucosidase inhibitory activities with IC50 of 8.72 μg/mL and 3.67 μg/mL, respectively. We find that FC show competitive inhibition against α-glucosidase, while the TC exhibits noncompetitive inhibition. Furthermore, The FC exhibits significant radical scavenging activity with the EC50 values of 7.73 μg/mL, 3.64 μg/mL and 5.90 μg/mL on DPPH radical, hydroxyl radical and ABTS radical, respectively. The FC also shows moderate anti-lipid peroxidation activity with the IC50 values of 41.77 μg/mL on inhibiting β-carotene bleaching. These results imply that the FC and the TC could be

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

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.

LC and LD50 values of Bacillus thuringiensis Serovar japonensis strain buibui toxin to Oriental beetle and northern masked chafer larvae (Coleoptera: Scarabaeidae).

PubMed

Mashtoly, Tamer A; El-Zemaity, Mohamed El-Said; Hussien, Mohamed I; Alm, Steven R

2009-10-01

Bacillus thuringiensis serovar japonensis strain Buibui has the potential to be an important control agent for pest scarabs. Bioassays were designed to test B. t. japonensis against two of the major turf and ornamental scarab pests infesting turfgrasses and ornamentals and to serve as a basis for further tests against other scarab pests. LC and LD50 values of B. t. serovarjaponensis strain Buibui toxin and spores were determined by four different bioassays for the oriental beetle, Anomala orientalis (Waterhouse), and northern masked chafer, Cyclocephala borealis Arrow. Oriental beetle larvae were bioassayed in autoclaved and nonautoclaved soil from where they were collected (Kingston, RI [native]), in nonautoclaved soil from where the northern masked chafer larvae were collected (Groton, CT [foreign]), and per os. Northern masked chafer larvae were bioassayed in autoclaved and nonautoclaved soil from where they were collected (Groton, CT [native]), in nonautoclaved soil from where the oriental beetle larvae were collected (Kingston, RI [foreign]) and per os. LC50 values of 3.93 microg toxin/g autoclaved native soil, 1.80 microg toxin/g nonautoclaved native soil, and 0.42 microg toxin/g nonautoclaved foreign soil and an LD50 value of 0.41 microg per os were determined at 14 d forA. orientalis. LC50 values of 588.28 microg toxin/g autoclaved native soil, 155.10 microg toxin/g nonautoclaved native soil, 265.32 microg toxin/g nonautoclaved foreign soil, and LD50 of 5.21 microg per os were determined at 14 d (soils) and 10 d (per os) for C. borealis. There were significant differences in LC50 values for oriental beetles in autoclaved, nonautoclaved native soil and nonautoclaved foreign soil. There were significant differences in LCo values for northern masked chafers in autoclaved and nonautoclaved native soil. B. t. japonensis can be applied now for control of oriental beetles at rates that are economically competitive with synthetic chemicals. If we can determine the

VLBA DETERMINATION OF THE DISTANCE TO NEARBY STAR-FORMING REGIONS. IV. A PRELIMINARY DISTANCE TO THE PROTO-HERBIG AeBe STAR EC 95 IN THE SERPENS CORE

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

Dzib, Sergio; Loinard, Laurent; Rodriguez, Luis F.

2010-08-01

Using the Very Long Base Array, we observed the young stellar object EC 95 in the Serpens cloud core at eight epochs from 2007 December to 2009 December. Two sources are detected in our field and are shown to form a tight binary system. The primary (EC 95a) is a 4-5 M {sub sun} proto-Herbig AeBe object (arguably the youngest such object known), whereas the secondary (EC 95b) is most likely a low-mass T Tauri star. Interestingly, both sources are non-thermal emitters. While T Tauri stars are expected to power a corona because they are convective while they go downmore » the Hayashi track, intermediate-mass stars approach the main sequence on radiative tracks. Thus, they are not expected to have strong superficial magnetic fields, and should not be magnetically active. We review several mechanisms that could produce the non-thermal emission of EC 95a and argue that the observed properties of EC 95a might be most readily interpreted if it possessed a corona powered by a rotation-driven convective layer. Using our observations, we show that the trigonometric parallax of EC 95 is {pi} = 2.41 {+-} 0.02 mas, corresponding to a distance of 414.9{sup +4.4} {sub -4.3} pc. We argue that this implies a distance to the Serpens core of 415 {+-} 5 pc and a mean distance to the Serpens cloud of 415 {+-} 25 pc. This value is significantly larger than previous estimates (d {approx} 260 pc) based on measurements of the extinction suffered by stars in the direction of Serpens. A possible explanation for this discrepancy is that these previous observations picked out foreground dust clouds associated with the Aquila Rift system rather than Serpens itself.« less

Inhibitors of plasmodial serine hydroxymethyltransferase (SHMT): cocrystal structures of pyrazolopyrans with potent blood- and liver-stage activities.

PubMed

Witschel, Matthias C; Rottmann, Matthias; Schwab, Anatol; Leartsakulpanich, Ubolsree; Chitnumsub, Penchit; Seet, Michael; Tonazzi, Sandro; Schwertz, Geoffrey; Stelzer, Frank; Mietzner, Thomas; McNamara, Case; Thater, Frank; Freymond, Céline; Jaruwat, Aritsara; Pinthong, Chatchadaporn; Riangrungroj, Pinpunya; Oufir, Mouhssin; Hamburger, Matthias; Mäser, Pascal; Sanz-Alonso, Laura M; Charman, Susan; Wittlin, Sergio; Yuthavong, Yongyuth; Chaiyen, Pimchai; Diederich, François

2015-04-09

Several of the enzymes related to the folate cycle are well-known for their role as clinically validated antimalarial targets. Nevertheless for serine hydroxymethyltransferase (SHMT), one of the key enzymes of this cycle, efficient inhibitors have not been described so far. On the basis of plant SHMT inhibitors from an herbicide optimization program, highly potent inhibitors of Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) SHMT with a pyrazolopyran core structure were identified. Cocrystal structures of potent inhibitors with PvSHMT were solved at 2.6 Å resolution. These ligands showed activity (IC50/EC50 values) in the nanomolar range against purified PfSHMT, blood-stage Pf, and liver-stage P. berghei (Pb) cells and a high selectivity when assayed against mammalian cell lines. Pharmacokinetic limitations are the most plausible explanation for lack of significant activity of the inhibitors in the in vivo Pb mouse malaria model.

Inhibition of S-adenosylmethionine decarboxylase and diamine oxidase activities by analogues of methylglyoxal bis(guanylhydrazone) and their cellular uptake during lymphocyte activation.

PubMed Central

Jänne, J; Morris, D R

1984-01-01

Several congeners of methylglyoxal bis(guanylhydrazone) were tested for their ability to inhibit eukaryotic putrescine-activated S-adenosylmethionine decarboxylase (EC 4.1.1.50) and intestinal diamine oxidase (EC 1.4.3.6). All the compounds tested, namely methylglyoxal bis(guanylhydrazone), ethylglyoxal bis(guanylhydrazone), dimethylglyoxal bis(guanylhydrazone) and the di-N"-methyl derivative of methylglyoxal bis(guanylhydrazone), were strong inhibitors of both yeast and mouse liver adenosylmethionine decarboxylase activity in vitro. The enzyme from both sources was most powerfully inhibited by ethylglyoxal bis(guanylhydrazone). All the diguanidines likewise inhibited diamine oxidase activity in vitro. The maximum intracellular concentrations of the ethyl and dimethylated analogues achieved in activated lymphocytes were only about one-fifth of that of the parent compound. However, both derivatives appeared to utilize the polyamine-carrier system, as indicated by competition experiments with spermidine. PMID:6426466

Inhibition of S-adenosylmethionine decarboxylase and diamine oxidase activities by analogues of methylglyoxal bis(guanylhydrazone) and their cellular uptake during lymphocyte activation.

PubMed

Jänne, J; Morris, D R

1984-03-15

Several congeners of methylglyoxal bis(guanylhydrazone) were tested for their ability to inhibit eukaryotic putrescine-activated S-adenosylmethionine decarboxylase (EC 4.1.1.50) and intestinal diamine oxidase (EC 1.4.3.6). All the compounds tested, namely methylglyoxal bis(guanylhydrazone), ethylglyoxal bis(guanylhydrazone), dimethylglyoxal bis(guanylhydrazone) and the di-N"-methyl derivative of methylglyoxal bis(guanylhydrazone), were strong inhibitors of both yeast and mouse liver adenosylmethionine decarboxylase activity in vitro. The enzyme from both sources was most powerfully inhibited by ethylglyoxal bis(guanylhydrazone). All the diguanidines likewise inhibited diamine oxidase activity in vitro. The maximum intracellular concentrations of the ethyl and dimethylated analogues achieved in activated lymphocytes were only about one-fifth of that of the parent compound. However, both derivatives appeared to utilize the polyamine-carrier system, as indicated by competition experiments with spermidine.

50 CFR 13.26 - Discontinuance of permit activity.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 1 2010-10-01 2010-10-01 false Discontinuance of permit activity. 13.26 Section 13.26 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR... PLANTS GENERAL PERMIT PROCEDURES Permit Administration § 13.26 Discontinuance of permit activity. When a...

50 CFR 18.117 - What activities are prohibited?

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 9 2014-10-01 2014-10-01 false What activities are prohibited? 18.117 Section 18.117 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR... What activities are prohibited? (a) Intentional take and lethal incidental take of walruses or polar...

Inhibition of Cancer-Associated Mutant Isocitrate Dehydrogenases: Synthesis, Structure–Activity Relationship, and Selective Antitumor Activity

PubMed Central

2015-01-01

Mutations of isocitrate dehydrogenase 1 (IDH1) are frequently found in certain cancers such as glioma. Different from the wild-type (WT) IDH1, the mutant enzymes catalyze the reduction of α-ketoglutaric acid to d-2-hydroxyglutaric acid (D2HG), leading to cancer initiation. Several 1-hydroxypyridin-2-one compounds were identified to be inhibitors of IDH1(R132H). A total of 61 derivatives were synthesized, and their structure–activity relationships were investigated. Potent IDH1(R132H) inhibitors were identified with Ki values as low as 140 nM, while they possess weak or no activity against WT IDH1. Activities of selected compounds against IDH1(R132C) were found to be correlated with their inhibitory activities against IDH1(R132H), as well as cellular production of D2HG, with R2 of 0.83 and 0.73, respectively. Several inhibitors were found to be permeable through the blood–brain barrier in a cell-based model assay and exhibit potent and selective activity (EC50 = 0.26–1.8 μM) against glioma cells with the IDH1 R132H mutation. PMID:25271760

Synthesis and proapoptotic activity of oleanolic acid derived amides.

PubMed

Heller, Lucie; Knorrscheidt, Anja; Flemming, Franziska; Wiemann, Jana; Sommerwerk, Sven; Pavel, Ioana Z; Al-Harrasi, Ahmed; Csuk, René

2016-10-01

Thirty-one different 3-O-acetyl-OA derived amides have been prepared and screened for their cytotoxic activity. In the SRB assays nearly all the carboxamides displayed good cytotoxicity in the low μM range for several human tumor cell lines. Low EC50 values were obtained especially for the picolinylamides 14-16, for a N-[2-(dimethylamino)-ethyl] derivative 27 and a N-[2-(pyrrolinyl)-ethyl] carboxamide 28. These compounds were submitted to an extensive biological testing and proved compound 15 to act mainly by an arrest of the tumor cells in the S phase of the cell cycle. Cell death occurred by autophagy while compounds 27 and 28 triggered apoptosis. Copyright © 2016 Elsevier Inc. All rights reserved.

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

High-resolution vertical profiles of groundwater electrical conductivity (EC) and chloride from direct-push EC logs

NASA Astrophysics Data System (ADS)

Bourke, Sarah A.; Hermann, Kristian J.; Hendry, M. Jim

2017-11-01

Elevated groundwater salinity associated with produced water, leaching from landfills or secondary salinity can degrade arable soils and potable water resources. Direct-push electrical conductivity (EC) profiling enables rapid, relatively inexpensive, high-resolution in-situ measurements of subsurface salinity, without requiring core collection or installation of groundwater wells. However, because the direct-push tool measures the bulk EC of both solid and liquid phases (ECa), incorporation of ECa data into regional or historical groundwater data sets requires the prediction of pore water EC (ECw) or chloride (Cl-) concentrations from measured ECa. Statistical linear regression and physically based models for predicting ECw and Cl- from ECa profiles were tested on a brine plume in central Saskatchewan, Canada. A linear relationship between ECa/ECw and porosity was more accurate for predicting ECw and Cl- concentrations than a power-law relationship (Archie's Law). Despite clay contents of up to 96%, the addition of terms to account for electrical conductance in the solid phase did not improve model predictions. In the absence of porosity data, statistical linear regression models adequately predicted ECw and Cl- concentrations from direct-push ECa profiles (ECw = 5.48 ECa + 0.78, R 2 = 0.87; Cl- = 1,978 ECa - 1,398, R 2 = 0.73). These statistical models can be used to predict ECw in the absence of lithologic data and will be particularly useful for initial site assessments. The more accurate linear physically based model can be used to predict ECw and Cl- as porosity data become available and the site-specific ECw-Cl- relationship is determined.

In Vitro Antioxidant and Antiproliferative Activities of Novel Orange Peel Extract and It's Fractions on Leukemia HL-60 Cells.

PubMed

Diab, Kawthar A E; Shafik, Reham Ezzat; Yasuda, Shin

2015-01-01

In the present work, novel orange peel was extracted with 100%EtOH (ethanol) and fractionated into four fractions namely F1, F2, F3, F4 which were eluted from paper chromatographs using 100%EtOH, 80%EtOH, 50%EtOH and pure water respectively. The crude extract and its four fractions were evaluated for their total polyphenol content (TPC), total flavonoid content (TFC) and radical scavenging activity using DPPH (1,1-diphenyl-2-picrylhydrazyl) assay. Their cytotoxic activity using WST assay and DNA damage by agarose gel electrophoresis were also evaluated in a human leukemia HL-60 cell line. The findings revealed that F4 had the highest TPC followed by crude extract, F2, F3 and F1. However, the crude extract had the highest TFC followed by F4, F3, F2, and F1. Depending on the values of EC50 and trolox equivalent antioxidant capacity, F4 possessed the strongest antioxidant activity while F1 and F2 displayed weak antioxidant activity. Further, incubation HL-60 cells with extract/fractions for 24h caused an inhibition of cell viability in a concentration- dependent manner. F3 and F4 exhibited a high antiproliferative activity with a narrow range of IC50 values (45.9 - 48.9 μg/ml). Crude extract exhibited the weakest antiproliferative activity with an IC50 value of 314.89 μg/ml. Analysis of DNA fragmentation displayed DNA degradation in the form of a smear-type pattern upon agarose gel after incubation of HL-60 cells with F3 and F4 for 6 h. Overall, F3 and F4 appear to be good sources of phytochemicals with antioxidant and potential anticancer activities.

50 CFR 18.127 - What activities are prohibited?

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 9 2014-10-01 2014-10-01 false What activities are prohibited? 18.127 Section 18.127 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR... § 18.127 What activities are prohibited? (a) Intentional take and lethal incidental take of polar bears...

50 CFR 22.12 - What activities are illegal?

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 9 2014-10-01 2014-10-01 false What activities are illegal? 22.12 Section 22.12 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR... WILDLIFE AND PLANTS (CONTINUED) EAGLE PERMITS General Requirements § 22.12 What activities are illegal? (a...

Regulation (EC) No 1901/2006 on medicinal products for paediatric use & clinical research in vulnerable populations

PubMed Central

Lehmann, Birka

2008-01-01

Before any medicinal product is authorised for use in adults, it must undergo extensive pharmaceutical consistency and stability tests, toxicological tests and clinical trials to ensure that it is of high quality, safe and effective. The same approach may not always be applied to medicinal products used to treat children. Studies showed that over 50% of the medicinal products used in children may not have been tested for use in this age group. The absence of suitable authorised medicinal products to treat conditions in children results from the fact that pharmaceutical companies do not adapt medicinal products to the needs of the paediatric population. This leaves health care professionals with no alternative other than to use medicinal products "off-label" and to use unauthorised products with the associated risks of inefficacy and/or adverse reactions. The Regulation (EC) No 1901/2006 sets up a system of requirements, rewards and incentives, together with horizontal measures, to ensure that medicinal products are researched, developed and authorised to meet the therapeutic needs of children. The Regulation is addressed to: 1. The pharmaceutical industry by setting out the legal framework for receiving rewards and incentives by conducting clinical trials in the paediatric population. 2. The Member States to set out to support research into, and the development and availability of, medicinal products for paediatric use. 3. The Community as funds for research into medicinal products for the paediatric population shall be provided for in the Community budget in order to support studies relating to medicinal products or active substances not covered by a patent or a supplementary protection certificate. The legal framework for conducting clinical trials, including children/minors, is set up in Directive 2001/20/EC, the Clinical Trials Directive (CTD), for the European Union (EU). The CTD establishes specific provisions regarding conduct of clinical trials, including

New positive Ca2+-activated K+ channel gating modulators with selectivity for KCa3.1.

PubMed

Coleman, Nichole; Brown, Brandon M; Oliván-Viguera, Aida; Singh, Vikrant; Olmstead, Marilyn M; Valero, Marta Sofia; Köhler, Ralf; Wulff, Heike

2014-09-01

Small-conductance (KCa2) and intermediate-conductance (KCa3.1) calcium-activated K(+) channels are voltage-independent and share a common calcium/calmodulin-mediated gating mechanism. Existing positive gating modulators like EBIO, NS309, or SKA-31 activate both KCa2 and KCa3.1 channels with similar potency or, as in the case of CyPPA and NS13001, selectively activate KCa2.2 and KCa2.3 channels. We performed a structure-activity relationship (SAR) study with the aim of optimizing the benzothiazole pharmacophore of SKA-31 toward KCa3.1 selectivity. We identified SKA-111 (5-methylnaphtho[1,2-d]thiazol-2-amine), which displays 123-fold selectivity for KCa3.1 (EC50 111 ± 27 nM) over KCa2.3 (EC50 13.7 ± 6.9 μM), and SKA-121 (5-methylnaphtho[2,1-d]oxazol-2-amine), which displays 41-fold selectivity for KCa3.1 (EC50 109 nM ± 14 nM) over KCa2.3 (EC50 4.4 ± 1.6 μM). Both compounds are 200- to 400-fold selective over representative KV (KV1.3, KV2.1, KV3.1, and KV11.1), NaV (NaV1.2, NaV1.4, NaV1.5, and NaV1.7), as well as CaV1.2 channels. SKA-121 is a typical positive-gating modulator and shifts the calcium-concentration response curve of KCa3.1 to the left. In blood pressure telemetry experiments, SKA-121 (100 mg/kg i.p.) significantly lowered mean arterial blood pressure in normotensive and hypertensive wild-type but not in KCa3.1(-/-) mice. SKA-111, which was found in pharmacokinetic experiments to have a much longer half-life and to be much more brain penetrant than SKA-121, not only lowered blood pressure but also drastically reduced heart rate, presumably through cardiac and neuronal KCa2 activation when dosed at 100 mg/kg. In conclusion, with SKA-121, we generated a KCa3.1-specific positive gating modulator suitable for further exploring the therapeutical potential of KCa3.1 activation. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

50 CFR 654.27 - Specifically authorized activities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Specifically authorized activities. 654.27 Section 654.27 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE STONE CRAB FISHERY OF THE GULF OF MEXICO Management...

Assessment of diclofenac LC50 reference values in juvenile and embryonic stages of the zebrafish (Danio rerio).

PubMed

Praskova, E; Voslarova, E; Siroka, Z; Plhalova, L; Macova, S; Marsalek, P; Pistekova, V; Svobodova, Z

2011-01-01

The aim of the study was to compare the acute toxicity of diclofenac to juvenile and embryonic stages of the zebrafish (Danio rerio). Acute toxicity tests were performed on the aquarium fish Danio rerio, which is one of the model organisms most commonly used in toxicity testing. The tests were performed using a semi-static method according to OECD guideline No. 203 (Fish, acute toxicity test). Embryo toxicity tests were performed in zebrafish embryos (Danio rerio) in compliance with OECD No. 212 methodology (Fish, short-term toxicity test on embryo and sac-fry stages). The results were subjected to a probit analysis using the EKO-TOX 5.2 programme to determine 96hLC50 and 144hLC50 (median lethal concentration, 50% mortality after a 96 h or 144 h interval, respectively) values of diclofenac. The statistical significance of the difference between LC50 values in juvenile and embryonic stages of Danio rerio was tested using the Mann-Whitney non-parametric test implemented in the Unistat 5.1 programme. The LC50 mean value of diclofenac was 166.6 +/- 9.8 mg/L in juvenile Danio rerio, and 6.11 +/- 2.48 mg/L in embryonic stages of Danio rerio. The study demonstrated a statistically higher sensitivity to diclofenac (P < 0.05) in embryonic stages compared to the juvenile fish.

Active inference and epistemic value.

PubMed

Friston, Karl; Rigoli, Francesco; Ognibene, Dimitri; Mathys, Christoph; Fitzgerald, Thomas; Pezzulo, Giovanni

2015-01-01

We offer a formal treatment of choice behavior based on the premise that agents minimize the expected free energy of future outcomes. Crucially, the negative free energy or quality of a policy can be decomposed into extrinsic and epistemic (or intrinsic) value. Minimizing expected free energy is therefore equivalent to maximizing extrinsic value or expected utility (defined in terms of prior preferences or goals), while maximizing information gain or intrinsic value (or reducing uncertainty about the causes of valuable outcomes). The resulting scheme resolves the exploration-exploitation dilemma: Epistemic value is maximized until there is no further information gain, after which exploitation is assured through maximization of extrinsic value. This is formally consistent with the Infomax principle, generalizing formulations of active vision based upon salience (Bayesian surprise) and optimal decisions based on expected utility and risk-sensitive (Kullback-Leibler) control. Furthermore, as with previous active inference formulations of discrete (Markovian) problems, ad hoc softmax parameters become the expected (Bayes-optimal) precision of beliefs about, or confidence in, policies. This article focuses on the basic theory, illustrating the ideas with simulations. A key aspect of these simulations is the similarity between precision updates and dopaminergic discharges observed in conditioning paradigms.

50 Hz sinusoidal magnetic fields do not affect human lymphocyte activation and proliferation in vitro

NASA Astrophysics Data System (ADS)

Capri, Miriam; Mesirca, Pietro; Remondini, Daniel; Carosella, Simona; Pasi, Sara; Castellani, Gastone; Franceschi, Claudio; Bersani, Ferdinando

2004-12-01

In the last 30 years, an increasing public concern about the possible harmful effects of electromagnetic fields generated by power lines and domestic appliances has pushed the scientific community to search for a correct and comprehensive answer to this problem. In this work the effects of exposure to 50 Hz sinusoidal magnetic fields, with a magnetic flux density of 0.05 mT and 2.5 mT (peak values), were studied on human peripheral blood mononuclear cells (PBMCs) collected from healthy young and elderly donors. Cell activation and proliferation were investigated by using flow cytometry techniques and 3H-TdR incorporation assays, respectively. The results obtained indicated that exposure to the fields altered neither DNA synthesis nor the capacity of lymphocytes to enter the activation phase and progress into the cell cycle. Thus, the conclusions are that two important functional phases of human lymphocytes, such as activation and proliferation, are not affected by exposures to 50 Hz magnetic fields similar to those found under power lines.

Corexit-EC9527A Disrupts Retinol Signaling and Neuronal Differentiation in P19 Embryonal Pluripotent Cells

DOE PAGES

Chen, Yanling; Reese, David H.; Kelly, Gregory M.

2016-09-29

Corexit-EC9500A and Corexit-EC9527A are two chemical dispersants that have been used to remediate the impact of the 2010 Deepwater Horizon oil spill. Both dispersants are composed primarily of organic solvents and surfactants and act by emulsifying the crude oil to facilitate biodegradation. The potential adverse effect of the Corexit chemicals on mammalian embryonic development remains largely unknown. Retinol (vitamin A) signaling, mediated by all-trans retinoic acid (RA), is essential for neural tube formation and the development of many organs in the embryo. The physiological levels of RA in cells and tissues are maintained by the retinol signaling pathway (RSP), whichmore » controls the biosynthesis of RA from dietary retinol and the catabolism of RA to polar metabolites for removal. RA is a potent activating ligand for the RAR/RXR nuclear receptors. Through RA and the receptors, the RSP modulates the expression of many developmental genes; interference with the RSP is potentially teratogenic. In this study the mouse P19 embryonal pluripotent cell, which contains a functional RSP, was used to evaluate the effects of the Corexit dispersants on retinol signaling and associated neuronal differentiation. The results showed that Corexit-EC9500A was more cytotoxic than Corexit-EC9527A to P19 cells. At non-cytotoxic doses, Corexit-EC9527A inhibited retinol-induced expression of the Hoxa1 gene, which encodes a transcription factor for the regulation of body patterning in the embryo. Such inhibition was seen in the retinol- and retinal- induced, but not RA-induced, Hoxa1 up-regulation, indicating that the Corexit chemicals primarily inhibit RA biosynthesis from retinal. In addition, Corexit-EC9527A suppressed retinol-induced P19 cell differentiation into neuronal cells, indicating potential neurotoxic effect of the chemicals under the tested conditions. In conclusion, the surfactant ingredient, dioctyl sodium sulfosuccinate (DOSS), may be a major contributor to the

Corexit-EC9527A Disrupts Retinol Signaling and Neuronal Differentiation in P19 Embryonal Pluripotent Cells

PubMed Central

Chen, Yanling; Reese, David H.

2016-01-01

Corexit-EC9500A and Corexit-EC9527A are two chemical dispersants that have been used to remediate the impact of the 2010 Deepwater Horizon oil spill. Both dispersants are composed primarily of organic solvents and surfactants and act by emulsifying the crude oil to facilitate biodegradation. The potential adverse effect of the Corexit chemicals on mammalian embryonic development remains largely unknown. Retinol (vitamin A) signaling, mediated by all-trans retinoic acid (RA), is essential for neural tube formation and the development of many organs in the embryo. The physiological levels of RA in cells and tissues are maintained by the retinol signaling pathway (RSP), which controls the biosynthesis of RA from dietary retinol and the catabolism of RA to polar metabolites for removal. RA is a potent activating ligand for the RAR/RXR nuclear receptors. Through RA and the receptors, the RSP modulates the expression of many developmental genes; interference with the RSP is potentially teratogenic. In this study the mouse P19 embryonal pluripotent cell, which contains a functional RSP, was used to evaluate the effects of the Corexit dispersants on retinol signaling and associated neuronal differentiation. The results showed that Corexit-EC9500A was more cytotoxic than Corexit-EC9527A to P19 cells. At non-cytotoxic doses, Corexit-EC9527A inhibited retinol-induced expression of the Hoxa1 gene, which encodes a transcription factor for the regulation of body patterning in the embryo. Such inhibition was seen in the retinol- and retinal- induced, but not RA-induced, Hoxa1 up-regulation, indicating that the Corexit chemicals primarily inhibit RA biosynthesis from retinal. In addition, Corexit-EC9527A suppressed retinol-induced P19 cell differentiation into neuronal cells, indicating potential neurotoxic effect of the chemicals under the tested conditions. The surfactant ingredient, dioctyl sodium sulfosuccinate (DOSS), may be a major contributor to the observed effect of

Corexit-EC9527A Disrupts Retinol Signaling and Neuronal Differentiation in P19 Embryonal Pluripotent Cells

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

Chen, Yanling; Reese, David H.; Kelly, Gregory M.

Corexit-EC9500A and Corexit-EC9527A are two chemical dispersants that have been used to remediate the impact of the 2010 Deepwater Horizon oil spill. Both dispersants are composed primarily of organic solvents and surfactants and act by emulsifying the crude oil to facilitate biodegradation. The potential adverse effect of the Corexit chemicals on mammalian embryonic development remains largely unknown. Retinol (vitamin A) signaling, mediated by all-trans retinoic acid (RA), is essential for neural tube formation and the development of many organs in the embryo. The physiological levels of RA in cells and tissues are maintained by the retinol signaling pathway (RSP), whichmore » controls the biosynthesis of RA from dietary retinol and the catabolism of RA to polar metabolites for removal. RA is a potent activating ligand for the RAR/RXR nuclear receptors. Through RA and the receptors, the RSP modulates the expression of many developmental genes; interference with the RSP is potentially teratogenic. In this study the mouse P19 embryonal pluripotent cell, which contains a functional RSP, was used to evaluate the effects of the Corexit dispersants on retinol signaling and associated neuronal differentiation. The results showed that Corexit-EC9500A was more cytotoxic than Corexit-EC9527A to P19 cells. At non-cytotoxic doses, Corexit-EC9527A inhibited retinol-induced expression of the Hoxa1 gene, which encodes a transcription factor for the regulation of body patterning in the embryo. Such inhibition was seen in the retinol- and retinal- induced, but not RA-induced, Hoxa1 up-regulation, indicating that the Corexit chemicals primarily inhibit RA biosynthesis from retinal. In addition, Corexit-EC9527A suppressed retinol-induced P19 cell differentiation into neuronal cells, indicating potential neurotoxic effect of the chemicals under the tested conditions. In conclusion, the surfactant ingredient, dioctyl sodium sulfosuccinate (DOSS), may be a major contributor to the

12 CFR 536.50 - Where insurance activities may take place.

Code of Federal Regulations, 2010 CFR

2010-01-01

....50 Section 536.50 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY CONSUMER PROTECTION IN SALES OF INSURANCE § 536.50 Where insurance activities may take place. (a) General rule. A... savings association may refer a consumer who seeks to purchase an insurance product or annuity to a...

Gamma irradiation induced enhancement of phenylalanine ammonia-lyase (PAL) and antioxidant activity in peach ( Prunus persica Bausch, Cv. Elberta)

NASA Astrophysics Data System (ADS)

Hussain, Peerzada R.; Wani, Ali M.; Meena, Raghuveer S.; Dar, Mohd A.

2010-09-01

Effect of medium dose gamma irradiation on PAL and antioxidant activity of peach fruit was investigated. Peach fruit after harvest at commercial maturity was irradiated in the dose range 1.0-2.0 kGy, stored under refrigerated conditions (3±1 °C, RH 80%) and evaluated at intervals of 7 days. The antioxidant activity as determined by DPPH and FRAP methods revealed significant ( p≤0.05) increase particularly in the dose range 1.6-2.0 kGy. During storage, maximum increase in both PAL and antioxidant activity was observed after 21 days. Positive correlation ( r=0.75) existed between antioxidant activity and total phenols. EC 50 values as obtained from DPPH and FRAP experiments were significantly ( p≤0.05) lower in irradiated fruits compared to control.

Low-EC-Content Electrolytes for Low-Temperature Li-Ion Cells

NASA Technical Reports Server (NTRS)

Smart, Marshall; Bugga, Ratnakumar; Surampudi, Subbarao

2003-01-01

Electrolytes comprising LiPF6 dissolved at a concentration of 1.0 M in three different mixtures of alkyl carbonates have been found well suited for use in rechargeable lithium-ion electrochemical cells at low temperatures. These and other electrolytes have been investigated in continuing research directed toward extending the lower limit of practical operating temperatures of Li-ion cells down to -60 C. This research at earlier stages was reported in numerous previous NASA Tech Briefs articles, the three most recent being "Ethyl Methyl Carbonate as a Cosolvent for Lithium-Ion Cells" (NPO-20605), Vol. 25, Low-EC-Content Electrolytes for Low-Temperature Li-Ion Cells No. 6 (June 2001), page 53; "Alkyl Pyrocarbonate Electrolyte Additives for Li-Ion Cells" (NPO-20775), Vol. 26, No. 5 (May 2002), page 37; and "Fluorinated Alkyl Carbonates as Cosolvents in Li-Ion Cells (NPO-21076), Vol. 26, No. 5 (May 2002), page 38. The present solvent mixtures, in terms of volume proportions of their ingredients, are 1 ethylene carbonate (EC) + 1 diethyl carbonate (DEC) + 1 dimethyl carbonate (DMC) + 3 ethyl methyl carbonate (EMC); 3EC + 3DMC + 14EMC; and 1EC + 1DEC + 1DMC + 4EMC. Relative to similar mixtures reported previously, the present mixtures, which contain smaller proportions of EC, have been found to afford better performance in experimental Li-ion cells at temperatures < -20 C.

Antibacterial, Antioxidant, and Anticholinesterase Activities of Plant Seed Extracts from Brazilian Semiarid Region

PubMed Central

Farias, Davi Felipe; Souza, Terezinha Maria; Viana, Martônio Ponte; Soares, Bruno Marques; Cunha, Arcelina Pacheco; Vasconcelos, Ilka Maria; Ricardo, Nágila Maria Pontes Silva; Ferreira, Paulo Michel Pinheiro; Melo, Vânia Maria Maciel; Carvalho, Ana Fontenele Urano

2013-01-01

The antimicrobial, antioxidant, and anticholinesterase activities of ethanolic seed extracts of twenty-one plant species from Brazilian semiarid region were investigated. The extracts were tested for antimicrobial activity against six bacteria strains and three yeasts. Six extracts presented activity against the Gram (−) organism Salmonella choleraesuis and the Gram (+) organisms Staphylococcus aureus and Bacillus subtilis. The MIC values ranged from 4.96 to 37.32 mg/mL. The Triplaris gardneriana extract presented activity against the three species, with MIC values 18.8, 13.76, and 11.15 mg/mL, respectively. Five extracts presented antioxidant activity, with EC50 values ranging from 69.73 μg/mL (T. gardneriana) to 487.51 μg/mL (Licania rigida). For the anticholinesterase activity, eleven extracts were capable of inhibiting the enzyme activity. From those, T. gardneriana, Parkia platycephala and Connarus detersus presented the best activities, with inhibition values of 76.7, 71.5, and 91.9%, respectively. The extracts that presented antimicrobial activity were tested for hemolytic assay against human A, B, and O blood types and rabbit blood. From those, only the Myracrodruon urundeuva extract presented activity (about 20% of hemolysis at the lowest tested concentration, 1.9 µg/mL). Infrared spectroscopy of six representative extracts attested the presence of tannins, polyphenols, and flavonoids, which was confirmed by a qualitative phytochemical assay. PMID:24386637

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.

Garcinia xanthochymus Benzophenones Promote Hyphal Apoptosis and Potentiate Activity of Fluconazole against Candida albicans Biofilms

PubMed Central

Jackson, Desmond N.; Yang, Lin; Wu, ShiBiao; Kennelly, Edward J.

2015-01-01

Xanthochymol and garcinol, isoprenylated benzophenones purified from Garcinia xanthochymus fruits, showed multiple activities against Candida albicans biofilms. Both compounds effectively prevented emergence of fungal germ tubes and were also cytostatic, with MICs of 1 to 3 μM. The compounds therefore inhibited development of hyphae and subsequent biofilm maturation. Xanthochymol treatment of developing and mature biofilms induced cell death. In early biofilm development, killing had the characteristics of apoptosis, including externalization of phosphatidyl serine and DNA fragmentation, as evidenced by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) fluorescence. These activities resulted in failure of biofilm maturation and hyphal death in mature biofilms. In mature biofilms, xanthochymol and garcinol caused the death of biofilm hyphae, with 50% effective concentrations (EC50s) of 30 to 50 μM. Additionally, xanthochymol-mediated killing was complementary with fluconazole against mature biofilms, reducing the fluconazole EC50 from >1,024 μg/ml to 13 μg/ml. Therefore, xanthochymol has potential as an adjuvant for antifungal treatments as well as in studies of fungal apoptosis. PMID:26195512

12 CFR 14.50 - Where insurance activities may take place.

Code of Federal Regulations, 2010 CFR

2010-01-01

....50 Section 14.50 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY CONSUMER PROTECTION IN SALES OF INSURANCE § 14.50 Where insurance activities may take place. (a) General rule. A bank... transactions are routinely conducted in the bank may refer a consumer who seeks to purchase an insurance...

Synthesis, characterization and monoamine transporter activity of the new psychoactive substance mexedrone and its N-methoxy positional isomer, N-methoxymephedrone.

PubMed

McLaughlin, Gavin; Morris, Noreen; Kavanagh, Pierce V; Power, John D; Dowling, Geraldine; Twamley, Brendan; O'Brien, John; Talbot, Brian; Walther, Donna; Partilla, John S; Baumann, Michael H; Brandt, Simon D

2017-03-01

3-Methoxy-2-(methylamino)-1-(4-methylphenyl)propan-1-one (mexedrone) appeared in 2015 and was advertised by UK Internet retailers as a non-controlled mephedrone derivative (2-(methylamino)-1-(4-methylphenyl)propan-1-one), which was of particular interest to countries who operate generic drugs legislation. This study describes the synthesis and analytical characterization of mexedrone and the differentiation from its isomer, N-methoxymephedrone, which was predicted to be a suitable candidate before the identity of mexedrone was revealed. A full analytical characterization is described using various chromatographic, spectroscopic and mass spectrometric platforms and X-ray crystal structure analysis. The analytical data obtained for a vendor sample were consistent with the synthesized mexedrone reference standard and analytical differentiation between the mexedrone and N-methoxymephedrone positional isomers was achieved. Furthermore, α-chloromethylmephedrone was identified as a by-product during mexedrone synthesis. All three substances were also studied for their uptake and releasing properties at dopamine transporters (DAT), norepinephrine transporters (NET) and serotonin transporters (SERT) using in vitro monoamine transporter assays in rat brain synaptosomes and compared to mephedrone. Mexedrone was a weak non-selective uptake blocker with IC 50 values in the low μM range. It was also devoid of releasing activity at DAT and NET but displayed weak releasing activity at SERT (EC 50  = 2.5 μM). The isomer N-methoxymephedrone was found to be a weak uptake blocker at DAT, NET and SERT, as well as a fully efficacious substrate-type releasing agent across all three transporters with EC 50 values in the low micromolar range. The synthesis by-product α-chloromethylmephedrone was inactive in all assays. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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

Effects of zinc and influence of Acremonium lolii on growth parameters, chlorophyll a fluorescence and antioxidant enzyme activities of ryegrass (Lolium perenne L. cv Apollo).

PubMed

Bonnet, M; Camares, O; Veisseire, P

2000-05-01

The effects of zinc on growth, mineral content, chlorophyll a fluorescence, and detoxifying enzyme activity (ascorbate peroxidase (APX), EC 1.11.1.11; superoxide dismutase (SOD), EC 1.15.1.1) of ryegrass infected or not by Acremonium lolii, and treated with nutrient solution containing 0-50 mM ZnSO(4) were studied. The introduction of zinc induces stress with a decrease in growth at 1, 5 and 10 mM ZnSO(4) and a cessation of growth at 50 mM ZnSO(4), in ryegrass plants infected by A. lolii or not. This decrease in growth may be due to an accumulation of zinc in leaves. Nevertheless, symbiotic plants showed higher values in tiller number, an advantage conferred by the fungus. After 24 d of Zn exposure, leaf fresh weights and leaf water content were lower in plants growing with Zn in the culture medium and no advantage was conferred by the fungus to its host. An increase in Zn supply resulted in a decrease of the Ca, K, Mg, and Cu content of the leaves, a reduction in the quantum yield of electron flow throughout photosystem II (DeltaF/F(1)(m))and a lowering of the efficiency of photosynthetic energy conversion (F(v)/F(m)), compared to control plants. To counter this zinc stress, detoxifying enzymes APX and SOD increased (100%) when Zn reached the value of 50 mM in the nutrient solution. At 10 mM ZnSO(4), the presence of the fungus in the plant led to an increase in the threshold toxicity of plants to zinc by a diminution of APX activity.

Differential vasoconstrictor activity of human urotensin-II in vascular tissue isolated from the rat, mouse, dog, pig, marmoset and cynomolgus monkey

PubMed Central

Douglas, Stephen A; Sulpizio, Anthony C; Piercy, Valerie; Sarau, Henry M; Ames, Robert S; Aiyar, Nambi V; Ohlstein, Eliot H; Willette, Robert N

2000-01-01

Urotensin-II (U-II) and its G-protein-coupled receptor, GPR14, are expressed within mammalian cardiac and peripheral vascular tissue and, as such, may regulate mammalian cardiovascular function. The present study details the vasoconstrictor profile of this cyclic undecapeptide in different vascular tissues isolated from a diverse range of mammalian species (rats, mice, dogs, pigs, marmosets and cynomolgus monkeys). The vasoconstrictor activity of human U-II was dependent upon the anatomical origin of the vessel studied and the species from which it was isolated. In the rat, constrictor responses were most pronounced in thoracic aortae and carotid arteries: −log[EC50]s 9.09±0.19 and 8.84±0.21, Rmaxs 143±21 and 67±26% 60 mM KCl, respectively (compared, for example, to −log[EC50] 7.90±0.11 and Rmax 142±12% 60 mM KCl for endothelin-1 [ET-1] in thoracic aortae). Responses were, however, absent in mice aortae (−log[EC50] <6.50). These findings were further contrasted by the observation that U-II was a ‘coronary-selective' spasmogen in the dog (−log[EC50] 9.46±0.11, Rmax 109±23% 60 mM KCl in LCX coronary artery), yet exhibited a broad spectrum of vasoconstrictor activity in arterial tissue from Old World monkeys (−log[EC50]s range from 8.96±0.15 to 9.92±0.13, Rmaxs from 43±16 to 527±135% 60 mM KCl). Interestingly, significant differences in reproducibility and vasoconstrictor efficacy were seen in tissue from pigs and New World primates (vessels which responded to noradrenaline, phenylephrine, KCl or ET-1 consistently). Thus, human U-II is a potent, efficacious vasoconstrictor of a variety of mammalian vascular tissues. Although significant species/anatomical variations exist, the data support the hypothesis that U-II influences the physiological regulation of mammalian cardiovascular function. PMID:11090097

Phosphatidylserine-mediated platelet clearance by endothelium decreases platelet aggregates and procoagulant activity in sepsis.

PubMed

Ma, Ruishuang; Xie, Rui; Yu, Chengyuan; Si, Yu; Wu, Xiaoming; Zhao, Lu; Yao, Zhipeng; Fang, Shaohong; Chen, He; Novakovic, Valerie; Gao, Chunyan; Kou, Junjie; Bi, Yayan; Thatte, Hemant S; Yu, Bo; Yang, Shufen; Zhou, Jin; Shi, Jialan

2017-07-10

The mechanisms that eliminate activated platelets in inflammation-induced disseminated intravascular coagulation (DIC) in micro-capillary circulation are poorly understood. This study explored an alternate pathway for platelet disposal mediated by endothelial cells (ECs) through phosphatidylserine (PS) and examined the effect of platelet clearance on procoagulant activity (PCA) in sepsis. Platelets in septic patients demonstrated increased levels of surface activation markers and apoptotic vesicle formation, and also formed aggregates with leukocytes. Activated platelets adhered were and ultimately digested by ECs in vivo and in vitro. Blocking PS on platelets or αvβ3 integrin on ECs attenuated platelet clearance resulting in increased platelet count in a mouse model of sepsis. Furthermore, platelet removal by ECs resulted in a corresponding decrease in platelet-leukocyte complex formation and markedly reduced generation of factor Xa and thrombin on platelets. Pretreatment with lactadherin significantly increased phagocytosis of platelets by approximately 2-fold, diminished PCA by 70%, prolonged coagulation time, and attenuated fibrin formation by 50%. Our results suggest that PS-mediated clearance of activated platelets by the endothelium results in an anti-inflammatory, anticoagulant, and antithrombotic effect that contribute to maintaining platelet homeostasis during acute inflammation. These results suggest a new therapeutic target for impeding the development of DIC.

Bidirectional juxtacrine ephrinB2/Ephs signaling promotes angiogenesis of ECs and maintains self-renewal of MSCs.

PubMed

Cao, Cen; Huang, Ying; Tang, Qingming; Zhang, Chenguang; Shi, Lei; Zhao, Jiajia; Hu, Li; Hu, Zhewen; Liu, Yun; Chen, Lili

2018-07-01

Co-transplantation of endothelial cells (ECs) and mesenchymal stem cells (MSCs) is an important strategy for repairing complex and large bone defects. However, the ways in which ECs and MSCs interact remain to be fully clarified. We found that forward ephrinB2/Ephs signaling from hBMSCs to hUVECs promoted the tube formation of hUVECs by activating the PI3K/AKT/mTOR pathway. Reverse ephrinB2/Ephs signaling from hUVECs to hBMSCs promoted the proliferation and maintenance of hBMSCs self-renewal via upregulation of OCT4, SOX2, and YAP1. Subcutaneous co-transplantation of ECs and MSCs in nude mice confirmed that forward ephrinB2/Ephs signaling could increase the cross-sectional area of blood vessels in the transplanted area, and reverse ephrinB2/Ephs signaling could maintain the self-renewal of transplanted hBMSCs in vivo. Based on these results, ephrinB2/Ephs bidirectional juxtacrine regulation between ECs and MSCs plays a pivotal role in improving the healing of bone defects by promoting angiogenesis and achieving a sufficient number of MSCs. Copyright © 2018 Elsevier Ltd. All rights reserved.

10 CFR 73.50 - Requirements for physical protection of licensed activities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Requirements for physical protection of licensed activities. 73.50 Section 73.50 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) PHYSICAL PROTECTION OF... suspicious activity or to the breaching of any physical barrier. (4) An isolation zone shall be maintained...

Manganese-dependent carboanhydrase activity of photosystem II proteins.

PubMed

Shitov, A V; Pobeguts, O V; Smolova, T N; Allakhverdiev, S I; Klimov, V V

2009-05-01

Four sources of carbonic anhydrase (CA) activity in submembrane preparations of photosystem II (PS II) isolated from pea leaves were examined. Three of them belong to the hydrophilic proteins of the oxygen-evolving complex of PS II with molecular mass 33 kDa (protein PsbO), 24 kDa (protein PsbP), and 18 kDa (protein PsbQ). The fourth source of CA activity is associated with a pigment-protein complex of PS II after removing three hydrophilic proteins by salt treatment. Except for protein PsbQ, the CA activity of all these proteins depends on the presence of Mn2+: the purified protein PsbO did not show CA activity before adding Mn2+ into the medium (concentration of Mn2+ required for 50% effect, EC(50), was 670 microM); CA activity of protein mixture composed of PsbP and PsbQ increased more than 5-fold upon adding Mn2+ (EC(50) was 45 microM). CA activity of purified protein PsbP increased 2-fold in the presence of 200 microM Mn2+. As indicated for the mixture of two proteins (PsbP and PsbQ), Mg2+, Ca2+, and Zn2+, in contrast to Mn2+, suppressed CA activity (both initial and Mn2+-induced activity). Since the found sources of CA activity demonstrated properties different from ones of typical CA (need for Mn2+, insensitivity or low sensitivity to acetazolamide or ethoxyzolamide) and such CA activity was found only among PS II proteins, we cannot exclude that they belong to the type of Mn-dependent CA associated with PS II.

Investigating added value of regional climate modeling in North American winter storm track simulations

NASA Astrophysics Data System (ADS)

Poan, E. D.; Gachon, P.; Laprise, R.; Aider, R.; Dueymes, G.

2018-03-01

Extratropical Cyclone (EC) characteristics depend on a combination of large-scale factors and regional processes. However, the latter are considered to be poorly represented in global climate models (GCMs), partly because their resolution is too coarse. This paper describes a framework using possibilities given by regional climate models (RCMs) to gain insight into storm activity during winter over North America (NA). Recent past climate period (1981-2005) is considered to assess EC activity over NA using the NCEP regional reanalysis (NARR) as a reference, along with the European reanalysis ERA-Interim (ERAI) and two CMIP5 GCMs used to drive the Canadian Regional Climate Model—version 5 (CRCM5) and the corresponding regional-scale simulations. While ERAI and GCM simulations show basic agreement with NARR in terms of climatological storm track patterns, detailed bias analyses show that, on the one hand, ERAI presents statistically significant positive biases in terms of EC genesis and therefore occurrence while capturing their intensity fairly well. On the other hand, GCMs present large negative intensity biases in the overall NA domain and particularly over NA eastern coast. In addition, storm occurrence over the northwestern topographic regions is highly overestimated. When the CRCM5 is driven by ERAI, no significant skill deterioration arises and, more importantly, all storm characteristics near areas with marked relief and over regions with large water masses are significantly improved with respect to ERAI. Conversely, in GCM-driven simulations, the added value contributed by CRCM5 is less prominent and systematic, except over western NA areas with high topography and over the Western Atlantic coastlines where the most frequent and intense ECs are located. Despite this significant added-value on seasonal-mean characteristics, a caveat is raised on the RCM ability to handle storm temporal `seriality', as a measure of their temporal variability at a given

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.

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

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.

EcR expression in the prothoracicotropic hormone-producing neurosecretory cells of the Bombyx mori brain.

PubMed

Hossain, Monwar; Shimizu, Sakiko; Fujiwara, Haruhiko; Sakurai, Sho; Iwami, Masafumi

2006-08-01

The steroid hormone 20-hydroxyecdysone (20E) initiates insect molting and metamorphosis through binding with a heterodimer of two nuclear receptors, the ecdysone receptor (EcR) and ultraspiracle (USP). Expression of the specific isoforms EcR-A and EcR-B1 governs steroid-induced responses in the developing cells of the silkworm Bombyx mori. Here, analysis of EcR-A and EcR-B1 expression during larval-pupal development showed that both genes were up-regulated by 20E in the B. mori brain. Whole-mount in situ hybridization and immunohistochemistry revealed that EcR-A and EcR-B1 mRNAs and proteins were exclusively located in two pairs of lateral neurosecretory cells in the larval brain known as the prothoracicotropic hormone (PTTH)- producing cells (PTPCs). In the pupal brain, EcR-A and EcR-B1 expression was detected in tritocerebral cells and optic lobe cells in addition to PTPCs. As PTTH controls ecdysone secretion by the prothoracic gland, these results indicate that 20E-responsive PTPCs are the master cells of insect metamorphosis.

Simulation of tropospheric chemistry and aerosols with the climate model EC-Earth

NASA Astrophysics Data System (ADS)

van Noije, T. P. C.; Le Sager, P.; Segers, A. J.; van Velthoven, P. F. J.; Krol, M. C.; Hazeleger, W.

2014-03-01

We have integrated the atmospheric chemistry and transport model TM5 into the global climate model EC-Earth version 2.4. We present an overview of the TM5 model and the two-way data exchange between TM5 and the integrated forecasting system (IFS) model from the European Centre for Medium-Range Weather Forecasts (ECMWF), the atmospheric general circulation model of EC-Earth. In this paper we evaluate the simulation of tropospheric chemistry and aerosols in a one-way coupled configuration. We have carried out a decadal simulation for present-day conditions and calculated chemical budgets and climatologies of tracer concentrations and aerosol optical depth. For comparison we have also performed offline simulations driven by meteorological fields from ECMWF's ERA-Interim reanalysis and output from the EC-Earth model itself. Compared to the offline simulations, the online-coupled system produces more efficient vertical mixing in the troposphere, which likely reflects an improvement of the treatment of cumulus convection. The chemistry in the EC-Earth simulations is affected by the fact that the current version of EC-Earth produces a cold bias with too dry air in large parts of the troposphere. Compared to the ERA-Interim driven simulation, the oxidizing capacity in EC-Earth is lower in the tropics and higher in the extratropics. The methane lifetime is 7% higher in EC-Earth, but remains well within the range reported in the literature. We evaluate the model by comparing the simulated climatologies of surface carbon monoxide, tropospheric and surface ozone, and aerosol optical depth against observational data. The work presented in this study is the first step in the development of EC-Earth into an Earth system model with fully interactive atmospheric chemistry and aerosols.

Simulation of tropospheric chemistry and aerosols with the climate model EC-Earth

NASA Astrophysics Data System (ADS)

van Noije, T. P. C.; Le Sager, P.; Segers, A. J.; van Velthoven, P. F. J.; Krol, M. C.; Hazeleger, W.; Williams, A. G.; Chambers, S. D.

2014-10-01

We have integrated the atmospheric chemistry and transport model TM5 into the global climate model EC-Earth version 2.4. We present an overview of the TM5 model and the two-way data exchange between TM5 and the IFS model from the European Centre for Medium-Range Weather Forecasts (ECMWF), the atmospheric general circulation model of EC-Earth. In this paper we evaluate the simulation of tropospheric chemistry and aerosols in a one-way coupled configuration. We have carried out a decadal simulation for present-day conditions and calculated chemical budgets and climatologies of tracer concentrations and aerosol optical depth. For comparison we have also performed offline simulations driven by meteorological fields from ECMWF's ERA-Interim reanalysis and output from the EC-Earth model itself. Compared to the offline simulations, the online-coupled system produces more efficient vertical mixing in the troposphere, which reflects an improvement of the treatment of cumulus convection. The chemistry in the EC-Earth simulations is affected by the fact that the current version of EC-Earth produces a cold bias with too dry air in large parts of the troposphere. Compared to the ERA-Interim driven simulation, the oxidizing capacity in EC-Earth is lower in the tropics and higher in the extratropics. The atmospheric lifetime of methane in EC-Earth is 9.4 years, which is 7% longer than the lifetime obtained with ERA-Interim but remains well within the range reported in the literature. We further evaluate the model by comparing the simulated climatologies of surface radon-222 and carbon monoxide, tropospheric and surface ozone, and aerosol optical depth against observational data. The work presented in this study is the first step in the development of EC-Earth into an Earth system model with fully interactive atmospheric chemistry and aerosols.

Activities of Jatropha curcas phorbol esters in various bioassays.

PubMed

Devappa, Rakshit K; Rajesh, Sanjay K; Kumar, Vikas; Makkar, Harinder P S; Becker, Klaus

2012-04-01

Jatropha curcas seeds contain 30-35% oil, which can be converted to high quality biodiesel. However, Jatropha oil is toxic, ascribed to the presence of phorbol esters (PEs). In this study, isolated phorbol ester rich fraction (PEEF) was used to evaluate the activity of PEs using three aquatic species based bioassays (snail (Physa fontinalis), brine shrimp (Artemeia salina), daphnia (Daphnia magna)) and microorganisms. In all the bioassays tested, increase in concentration of PEs increased mortality with an EC(50) (48 h) of 0.33, 26.48 and 0.95 mg L(-1) PEs for snail, artemia and daphnia, respectively. The sensitivity of various microorganisms for PEs was also tested. Among the bacterial species tested, Streptococcus pyogenes and Proteus mirabilis were highly susceptible with a minimum inhibitory concentration (MIC) of 215 mg L(-1) PEs; and Pseudomonas putida were also sensitive with MIC of 251 mg L(-1) PEs. Similarly, Fusarium species of fungi exhibited EC(50) of 58 mg L(-1) PEs, while Aspergillus niger and Curvularia lunata had EC(50) of 70 mg L(-1). The snail bioassay was most sensitive with 100% snail mortality at 1 μg of PEs mL(-1). In conclusion, snail bioassay could be used to monitor PEs in Jatropha derived products such as oil, biodiesel, fatty acid distillate, kernel meal, cake, glycerol or for contamination in soil or other environmental matrices. In addition, PEs with molluscicidal/antimicrobial activities could be utilized for agricultural and pharmaceutical applications. Copyright © 2011 Elsevier Inc. All rights reserved.

ECS: efficient communication scheduling for underwater sensor networks.

PubMed

Hong, Lu; Hong, Feng; Guo, Zhongwen; Li, Zhengbao

2011-01-01

TDMA protocols have attracted a lot of attention for underwater acoustic sensor networks (UWSNs), because of the unique characteristics of acoustic signal propagation such as great energy consumption in transmission, long propagation delay and long communication range. Previous TDMA protocols all allocated transmission time to nodes based on discrete time slots. This paper proposes an efficient continuous time scheduling TDMA protocol (ECS) for UWSNs, including the continuous time based and sender oriented conflict analysis model, the transmission moment allocation algorithm and the distributed topology maintenance algorithm. Simulation results confirm that ECS improves network throughput by 20% on average, compared to existing MAC protocols.

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

EC power management in ITER for NTM control: the path from the commissioning phase to demonstration discharges

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

Poli, Francesca M.; Fredrickson, Eric; Henderson, Mark A.

Time dependent simulations that evolve consistently the magnetic equilibrium and plasma pressure profiles and the width and frequency rotation of magnetic islands under the effect of the Electron Cyclotron feedback system are used to assess whether the control of NTMs on ITER is compatible with other simulataneous functionalities of the EC system, like core heating and current profile tailoring, or sawtooth control. Furthermore, results indicate that the power needs for control can be reduced if the EC power is reserved and if pre-emptive control is used as opposed to an active search for an already developed island.

EC power management in ITER for NTM control: the path from the commissioning phase to demonstration discharges

DOE PAGES

Poli, Francesca M.; Fredrickson, Eric; Henderson, Mark A.; ...

2017-10-23

Time dependent simulations that evolve consistently the magnetic equilibrium and plasma pressure profiles and the width and frequency rotation of magnetic islands under the effect of the Electron Cyclotron feedback system are used to assess whether the control of NTMs on ITER is compatible with other simulataneous functionalities of the EC system, like core heating and current profile tailoring, or sawtooth control. Furthermore, results indicate that the power needs for control can be reduced if the EC power is reserved and if pre-emptive control is used as opposed to an active search for an already developed island.

Prediction of ECS and SSC Models for Flux-Limited Samples of Gamma-Ray Blazars

NASA Technical Reports Server (NTRS)

Lister, Matthew L.; Marscher, Alan P.

1999-01-01

The external Compton scattering (ECS) and synchrotron self-Compton (SSC) models make distinct predictions for the amount of Doppler boosting of high-energy gamma-rays emitted by Nazar. We examine how these differences affect the predicted properties of active galactic nucleus (AGN) samples selected on the basis of Murray emission. We create simulated flux-limited samples based on the ECS and SSC models, and compare their properties to those of identified EGRET blazars. We find that for small gamma-ray-selected samples, the two models make very similar predictions, and cannot be reliably distinguished. This is primarily due to the fact that not only the Doppler factor, but also the cosmological distance and intrinsic luminosity play a role in determining whether an AGN is included in a flux-limited gamma-ray sample.

[Study on antioxidative activities of Psidium guajava Linn leaves extracts].

PubMed

Wang, Bo; Jiao, Shirong; Liu, Hengchuan; Hong, Junrong

2007-05-01

To study the antioxidative activities of the extracts from Psidium guajava Linn leaves (PGL). The PGL was submersed with distilled water, 65% ethanol and 95% ethanol respectively. The 3 extracts were obtained after the solutions were filtered, concentrated and dried. The scavenging rate to hydroxyl radicals and inhibiting rate to lipid peroxidation were analyzed for the 3 extracts. Their contents of total flavonoids were determined by ultraviolet spectrophotometry, and the components of total flavonoids were primarily identified by high performance liquid chromatography (HPLC) and ultraviolet-visible absorption spectrometry (UV). The extracts from distilled water, 65% ethanol and 95% ethanol respectively showed effects on scavenging hydroxyl radicals and inhibiting lipid peroxidation in the dose-dependent manner, had 50% effective concentration (EC50) on scavenging hydroxyl radicals of 0.63, 0.47 and 0.58g/L, had EC50 on inhibiting lipid peroxidation of 0.20, 0.035, 0.18g/L and had total flavonoids contents of 3.28, 30.71 and 55.98g/kg respectively. The aquatic and the ethanol extracts from PGL possess the potential antioxidative activities in the study. The flavonoids may be one of their antioxidative components.

Ethylene-induced gene expression, enzyme activities, and water soaking in immature and ripe watermelon (Citrullus lanatus) fruit.

PubMed

Karakurt, Yasar; Huber, Donald J

2004-04-01

Watermelon fruit exhibit acute softening and placental-tissue water soaking following short exposure to exogenous ethylene. Experiments were performed to address transcript abundance and activities of cell wall and membrane hydrolases in placental tissue in response to treatment of watermelon fruit with ethylene. Watermelon fruit were harvested at immature and full-ripe stages and exposed to 50 microL L(-1) ethylene for 6 days at 20 degrees C. Ethylene affected the abundance of transcripts for PME (EC 3.2.1.11), and alpha-(EC 3.2.1.22) and beta-GAL (EC 3.2.1.23) but these effects were dependent on fruit maturity and appeared not to be associated with the water-soaking syndrome. PG (EC 3.2.1.15) and EXP mRNAs accumulated significantly in response to ethylene exposure. Additionally, the levels of mRNA and activities of LOX (EC 1.13.11.12), PLC (EC 3.1.4.3) and PLD (EC 3.1.4.4) were elevated in fruit of both maturity classes exposed to ethylene and were temporally associated with the visible symptoms of water soaking. The activity trends and transcript abundance in ethylene- compared with air-treated fruit indicate that PG, EXP, LOX, PLC and PLD levels increase with the onset and development of the water-soaking disorder and support the view that catabolic reactions targeting the membranes and cell-walls contribute to the disorder.

Novel Phenolic Inhibitors of Small/Intermediate-Conductance Ca2+-Activated K+ Channels, KCa3.1 and KCa2.3

PubMed Central

Oliván-Viguera, Aida; Valero, Marta Sofía; Murillo, María Divina; Wulff, Heike; García-Otín, Ángel-Luis; Arbonés-Mainar, José-Miguel; Köhler, Ralf

2013-01-01

Background KCa3.1 channels are calcium/calmodulin-regulated voltage-independent K+ channels that produce membrane hyperpolarization and shape Ca2+-signaling and thereby physiological functions in epithelia, blood vessels, and white and red blood cells. Up-regulation of KCa3.1 is evident in fibrotic and inflamed tissues and some tumors rendering the channel a potential drug target. In the present study, we searched for novel potent small molecule inhibitors of KCa3.1 by testing a series of 20 selected natural and synthetic (poly)phenols, synthetic benzoic acids, and non-steroidal anti-inflammatory drugs (NSAIDs), with known cytoprotective, anti-inflammatory, and/or cytostatic activities. Methodology/Principal Findings In electrophysiological experiments, we identified the natural phenols, caffeic acid (EC50 1.3 µM) and resveratrol (EC50 10 µM) as KCa3.1 inhibitors with moderate potency. The phenols, vanillic acid, gallic acid, and hydroxytyrosol had weak or no blocking effects. Out of the NSAIDs, flufenamic acid was moderately potent (EC50 1.6 µM), followed by mesalamine (EC50≥10 µM). The synthetic fluoro-trivanillic ester, 13b ([3,5-bis[(3-fluoro-4-hydroxy-benzoyl)oxymethyl]phenyl]methyl 3-fluoro-4-hydroxy-benzoate), was identified as a potent mixed KCa2/3 channel inhibitor with an EC50 of 19 nM for KCa3.1 and 360 pM for KCa2.3, which affected KCa1.1 and Kv channels only at micromolar concentrations. The KCa3.1/KCa2-activator SKA-31 antagonized the 13b-blockade. In proliferation assays, 13b was not cytotoxic and reduced proliferation of 3T3 fibroblasts as well as caffeic acid. In isometric vessel myography, 13b increased contractions of porcine coronary arteries to serotonin and antagonized endothelium-derived hyperpolarization-mediated vasorelaxation to pharmacological KCa3.1/KCa2.3 activation. Conclusions/Significance We identified the natural phenols, caffeic acid and resveratrol, the NSAID, flufenamic acid, and the polyphenol 13b as novel KCa3

Application of the Activity Framework for Assessing Aquatic Ecotoxicology Data for Organic Chemicals.

PubMed

Thomas, Paul; Dawick, James; Lampi, Mark; Lemaire, Philippe; Presow, Shaun; van Egmond, Roger; Arnot, Jon A; Mackay, Donald; Mayer, Philipp; Galay Burgos, Malyka

2015-10-20

Toxicological research in the 1930s gave the first indications of the link between narcotic toxicity and the chemical activity of organic chemicals. More recently, chemical activity has been proposed as a novel exposure parameter that describes the fraction of saturation and that quantifies the potential for partitioning and diffusive uptake. In the present study, more than 2000 acute and chronic algal, aquatic invertebrates and fish toxicity data, as well as water solubility and melting point values, were collected from a series of sources. The data were critically reviewed and grouped by mode of action (MoA). We considered 660 toxicity data to be of acceptable quality. The 328 data which applied to the 72 substances identified as MoA 1 were then evaluated within the activity-toxicity framework: EC50 and LC50 values for all three taxa correlated generally well with (subcooled) liquid solubilities. Acute toxicity was typically exerted within the chemical activity range of 0.01-0.1, whereas chronic toxicity was exerted in the range of 0.001-0.01. These results confirm that chemical activity has the potential to contribute to the determination, interpretation and prediction of toxicity to aquatic organisms. It also has the potential to enhance regulation of organic chemicals by linking results from laboratory tests, monitoring and modeling programs. The framework can provide an additional line of evidence for assessing aquatic toxicity, for improving the design of toxicity tests, reducing animal usage and addressing chemical mixtures.

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.

Nuclear Factor Kappa B Activation and Peroxisome Proliferator-activated Receptor Transactivational Effects of Chemical Components of the Roots of Polygonum multiflorum.

PubMed

Sun, Ya Nan; Li, Wei; Song, Seok Bean; Yan, Xi Tao; Yang, Seo Young; Kim, Young Ho

2016-01-01

Polygonum multiflorum is well-known as "Heshouwu" in traditional Chinese herbal medicine. In Northeast Asia, it is often used as a tonic to prevent premature aging of the kidney and liver, tendons, and bones and strengthening of the lower back and knees. To research the anti-inflammatory activities of components from P. multiflorum. The compounds were isolated by a combination of silica gel and YMC R-18 column chromatography, and their structures were identified by analysis of spectroscopic data (1D, 2D-nuclear magnetic resonance, and mass spectrometry). The anti-inflammatory activities of the isolated compounds 1-15 were evaluated by luciferase reporter gene assays. Fifteen compounds (1-15) were isolated from the roots of P. multiflorum. Compounds 1-5 and 14-15 significantly inhibited tumor necrosis factor-α-induced nuclear factor kappa B-luciferase activity, with IC50 values of 24.16-37.56 μM. Compounds 1-5 also greatly enhanced peroxisome proliferator-activated receptors transcriptional activity with EC50 values of 18.26-31.45 μM. The anthraquinone derivatives were the active components from the roots of P. multiflorum as an inhibitor on inflammation-related factors in human hepatoma cells. Therefore, we suggest that the roots of P. multiflorum can be used to treat natural inflammatory diseases. This study presented that fifteen compounds (1-15) isolated from the roots of Polygonum multiflrum exert signifiant anti inflmmatory effects by inhibiting TNF α induced NF κB activation and PPARs transcription. Abbreviation used: NF κB: Nuclear factor kappa B, PPARs: Peroxisome proliferator activated receptors, PPREs: Peroxisome proliferator response elements, TNF α: Tumor necrosis factor α, ESI-MS: Electrospray ionization mass spectrometry, HepG2: Human hepatoma cells.

The Natural Plant Product Rottlerin Activates Kv7.1/KCNE1 Channels.

PubMed

Matschke, Veronika; Piccini, Ilaria; Schubert, Janina; Wrobel, Eva; Lang, Florian; Matschke, Johann; Amedonu, Elsie; Meuth, Sven G; Strünker, Timo; Strutz-Seebohm, Nathalie; Greber, Boris; Scherkenbeck, Jürgen; Seebohm, Guiscard

2016-01-01

Acquired as well as inherited channelopathies are disorders that are caused by altered ion channel function. A family of channels whose malfunction is associated with different channelopathies is the Kv7 K+ channel family; and restoration of normal Kv7 channel function by small molecule modulators is a promising approach for treatment of these often fatal diseases. Here, we show the modulation of Kv7 channels by the natural compound Rottlerin heterologously expressed in Xenopus laevis oocytes and on iPSC cardiomyocytes overexpressing Kv7.1 channels. We show that currents carried by Kv7.1 (EC50 = 1.48 μM), Kv7.1/KCNE1 (EC50 = 4.9 μM), and Kv7.4 (EC50 = 0.148 μM) are strongly enhanced by the compound, whereas Kv7.2, Kv7.2/Kv7.3, and Kv7.5 are not sensitive to Rottlerin. Studies on Kv7.1/KCNE1 mutants and in silico modelling indicate that Rottlerin binds to the R-L3-activator site. Rottlerin mediated activation of Kv7.1/KCNE1 channels might be a promising approach in long QT syndrome. As a proof of concept, we show that Rottlerin shortens cardiac repolarisation in iPSC-derived cardiomyocytes expressing Kv7.1. Rottlerin or an optimized derivative holds a potential as QT interval correcting drug. © 2016 The Author(s) Published by S. Karger AG, Basel.

The Association Between Low 50 g Glucose Challenge Test Values and Adverse Pregnancy Outcomes.

PubMed

Kwon, Hayan; Lee, Joonho; Lee, Byung-Wan; Kwon, Ja-Young; Kim, Young-Han

2018-01-11

The implications of low values on the 50 g glucose challenge test (GCT) in pregnancy are not clearly defined. Few studies have evaluated the influence of maternal low GCT values on obstetrical outcomes. This study aimed to compare pregnancy outcomes between women with low 50 g GCT values and those with normal values. Women undergoing gestational diabetes mellitus screening at 24-28 weeks of gestational age between January 2010 and December 2016 were retrospectively evaluated. Women with multifetal pregnancies, prepregnancy type I or II diabetes, GCT performed before 24 or after 28 weeks of gestational age, and women undergoing multiple GCTs in the same pregnancy were excluded. Low GCT values and normal GCT values were defined as ≤85 mg/dL and 86-130 mg/dL, respectively. Of 3875 screened subjects, 519 (13.4%) women were included in the low GCT group and 3356 (86.6%) in the normal GCT group. Low GCT women had a significantly higher rate of small for gestational age (SGA) infants than normal GCT women (10.8% vs. 7.9%, p = 0.02). Cesarean section and postpartum hemorrhage (PPH) were less frequent in low GCT women than in normal women (32.6% vs. 42.8%, p < 0.01 and 0.2% vs. 1.2%, p = 0.03, respectively). Low GCT women had a 1.38-fold increased risk of bearing SGA infants (95% confidence intervals: 1.01-1.88, p = 0.04). Rate of SGA infants was significantly higher and cesarean delivery and PPH rates were significantly lower in women with low GCT values. Low GCT values were independently associated with an increased risk of SGA.

Group I mGlu receptor stimulation inhibits activation-induced cell death of human T lymphocytes

PubMed Central

Chiocchetti, Annalisa; Miglio, Gianluca; Mesturini, Riccardo; Varsaldi, Federica; Mocellin, Marco; Orilieri, Elisabetta; Dianzani, Chiara; Fantozzi, Roberto; Dianzani, Umberto; Lombardi, Grazia

2006-01-01

The effects of L-glutamate on activation-induced cell death (AICD) of human activated (1 μg ml−1 phytohemagglutinin plus 2 U ml−1 interleukin-2; 8 days) T lymphocytes were studied by measuring anti-CD3 monoclonal antibody (10 μg ml−1; 18 h)-induced cell apoptosis (Annexin V and propidium iodide staining). L-Glutamate (1 × 10−8–1 × 10−4 M) significantly (P⩽0.01) inhibited AICD in a concentration-dependent manner (EC50=6.3 × 10−8 M; maximum inhibition 54.8±6.3% at 1 × 10−6 M). The L-glutamate inhibitory effect was pharmacologically characterized as mediated by group I mGlu receptors, since mGlu receptor agonists reproduced this effect. The EC50 values were: 3.2 × 10−7 M for (1S,3R)-ACPD; 4.5 × 10−8 M for quisqualate; 1.0 × 10−6 M for (S)-3,5-DHPG; 2.0 × 10−5 M for CHPG. Group I mGlu receptor antagonists inhibited the effects of quisqualate 1.0 × 10−6 M. The IC50 values calculated were: 8.7 × 10−5, 4.3 × 10−6 and 6.3 × 10−7 M for AIDA, LY 367385 and MPEP, respectively. L-Glutamate (1 × 10−6 M; 18 h) significantly (P⩽0.05) inhibited FasL expression (40.8±11.3%) (cytofluorimetric analysis), whereas it did not affect Fas signalling. Expression of both mGlu1 and mGlu5 receptor mRNA by T lymphocytes and T-cell lines, as demonstrated by reverse transcriptase–PCR analysis, suggests that L-glutamate-mediated inhibition of AICD was exerted on T cells. These data depict a novel role for L-glutamate in the regulation of the immune response through group I mGlu receptor-mediated mechanisms. PMID:16751798

50 CFR 600.745 - Scientific research activity, exempted fishing, and exempted educational activity.

Code of Federal Regulations, 2014 CFR

2014-10-01

... collection designed to capture and land quantities of fish for product development, market research, and/or... 50 Wildlife and Fisheries 12 2014-10-01 2014-10-01 false Scientific research activity, exempted...-STEVENS ACT PROVISIONS General Provisions for Domestic Fisheries § 600.745 Scientific research activity...

50 CFR 600.745 - Scientific research activity, exempted fishing, and exempted educational activity.

Code of Federal Regulations, 2012 CFR

2012-10-01

... collection designed to capture and land quantities of fish for product development, market research, and/or... 50 Wildlife and Fisheries 12 2012-10-01 2012-10-01 false Scientific research activity, exempted...-STEVENS ACT PROVISIONS General Provisions for Domestic Fisheries § 600.745 Scientific research activity...

50 CFR 600.745 - Scientific research activity, exempted fishing, and exempted educational activity.

Code of Federal Regulations, 2013 CFR

2013-10-01

... collection designed to capture and land quantities of fish for product development, market research, and/or... 50 Wildlife and Fisheries 12 2013-10-01 2013-10-01 false Scientific research activity, exempted...-STEVENS ACT PROVISIONS General Provisions for Domestic Fisheries § 600.745 Scientific research activity...

50 CFR 600.745 - Scientific research activity, exempted fishing, and exempted educational activity.

Code of Federal Regulations, 2011 CFR

2011-10-01

... collection designed to capture and land quantities of fish for product development, market research, and/or... 50 Wildlife and Fisheries 10 2011-10-01 2011-10-01 false Scientific research activity, exempted...-STEVENS ACT PROVISIONS General Provisions for Domestic Fisheries § 600.745 Scientific research activity...

50 CFR 600.745 - Scientific research activity, exempted fishing, and exempted educational activity.

Code of Federal Regulations, 2010 CFR

2010-10-01

... collection designed to capture and land quantities of fish for product development, market research, and/or... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Scientific research activity, exempted...-STEVENS ACT PROVISIONS General Provisions for Domestic Fisheries § 600.745 Scientific research activity...

10 CFR 73.50 - Requirements for physical protection of licensed activities.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false Requirements for physical protection of licensed activities. 73.50 Section 73.50 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) PHYSICAL PROTECTION OF PLANTS AND MATERIALS Physical Protection Requirements at Fixed Sites § 73.50 Requirements for physical...

10 CFR 73.50 - Requirements for physical protection of licensed activities.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 2 2013-01-01 2013-01-01 false Requirements for physical protection of licensed activities. 73.50 Section 73.50 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) PHYSICAL PROTECTION OF PLANTS AND MATERIALS Physical Protection Requirements at Fixed Sites § 73.50 Requirements for physical...

Proposed anti-HSV compounds isolated from Simira species.

PubMed

Cavalcanti, Jessica F; de Araujo, Marcelo F; Gonçalves, Priscila B; Romeiro, Nelilma C; Villela Romanos, Maria T; Curcino Vieira, Ivo J; Braz-Filho, Raimundo; de Carvalho, Mário G; Sanches, Mirza N G

2017-09-19

Secondary metabolites isolated from Simira eleiezeriana and Simira glaziovii were evaluated against herpes simplex virus (HSV-1) and (HSV-2). The 50% effective concentrations values (EC 50 ) were calculated from the dose-response curve and the selectivity index (SI) against the virus. The physicochemical data LogP, (PSA), (NRB), (HBA) and (HBD) were obtained using Marvin Sketch. Among the tested compounds, conipheraldeyde, harman and simirane A showed better results with EC 50 6.39; 4.90; 4.61 µg/mL and SI 78.3; 11.8; 7.01, respectively, for HSV-1, and EC 50 41.2; 71.8; 3.73 µg/mL and SI 12.1; 24.7; 8.7, respectively, for HSV-2. The percentage of inhibition (PI) obtained for HSV-1 were higher than 60%, and for HSV-2 these compounds showed PI > 90%. The physical chemical data showed that the most active compounds satisfy the attributes for drugs with good oral bioavailability.

ECS: Efficient Communication Scheduling for Underwater Sensor Networks

PubMed Central

Hong, Lu; Hong, Feng; Guo, Zhongwen; Li, Zhengbao

2011-01-01

TDMA protocols have attracted a lot of attention for underwater acoustic sensor networks (UWSNs), because of the unique characteristics of acoustic signal propagation such as great energy consumption in transmission, long propagation delay and long communication range. Previous TDMA protocols all allocated transmission time to nodes based on discrete time slots. This paper proposes an efficient continuous time scheduling TDMA protocol (ECS) for UWSNs, including the continuous time based and sender oriented conflict analysis model, the transmission moment allocation algorithm and the distributed topology maintenance algorithm. Simulation results confirm that ECS improves network throughput by 20% on average, compared to existing MAC protocols. PMID:22163775

Chemical and Bioactive Profiling, and Biological Activities of Coral Fungi from Northwestern Himalayas.

PubMed

Kumar Sharma, Sapan; Gautam, Nandini

2017-04-19

Ramaria Fr. and Clavaria L. are the two major genera of coral mushrooms within families Gomphaceae and Clavariaceae, respectively. Besides having important role in forest ecology, some species of these are reported to possess high nutraceutical and bioactive potential. There is a hidden diversity of coral mushrooms in Northwestern Himalayas. Present studies describe the detailed biochemical profiling and antioxidant, and antibacterial activities of twelve coral mushroom species. Biochemical profiling of nutrients and nutraceuticals was done with standard techniques and by using HPLC, UPLC and GC. Experiments were also conducted to check the toxic metals detection. Antioxidant activities were calculated using EC50 values from mushroom extracts. Antibacterial activities were checked on six pathogenic bacterial strains through minimum inhibition concenterations. Although, differences were observed in the net values of individual species but all the species were found to be rich in protein, macro and micro minerals, carbohydrates, unsaturated fatty acids, essential amino acids, phenolics, tocopherols, anthocynadins and carotenoids. All the species showed significant antioxidant and antibacterial activities. These species are reported to free from heavy toxic metals. Present studies will open the way for their large scale commercial exploitations and use in pharmaceutical industries as antioxidant, antibacterial and nutraceutical constituents.

Flight evaluation of Spacelab 1 payload thermal/ECS interfaces

NASA Technical Reports Server (NTRS)

Ray, C. D.; Humphries, W. R.; Patterson, W. C.

1984-01-01

The Spacelab (SL-1) thermal/Environmental Control Systems (ECS) are discussed. Preflight analyses and flight data are compared in order to validate payload to Spacelab interfaces as well as corroborate modeling/analysis techniques. In doing so, a brief description of the Spacelab 1 payload configuration and the interactive Spacelab thermal/ECS systems are given. In particular, these interfaces address equipment cooling air, thermal and fluid conditions, humidity levels, both freon and water loop temperatures and load states, as well as passive radiant environment interfaces.

Hibiscus sabdariffa L. and Its Bioactive Constituents Exhibit Antiviral Activity against HSV-2 and Anti-enzymatic Properties against Urease by an ESI-MS Based Assay.

PubMed

Hassan, Sherif T S; Švajdlenka, Emil; Berchová-Bímová, Kateřina

2017-04-30

For decades, Hibiscus sabdariffa L. and its phytochemicals have been shown to possess a wide range of pharmacologic properties. In this study, aqueous extract of Hibiscus sabdariffa (AEHS) and its bioactive constituent protocatechuic acid (PCA), have been evaluated in vitro for their antiviral activity against HSV-2 clinical isolates and anti-enzymatic activity against urease. Antiherpetic activity was evaluated by the titer reduction assay in infected Vero cells, and cytotoxicity was evaluated by the neutral red dye-uptake method. Anti-urease activity was determined by a developed Electrospray Ionization-Mass Spectrometry (ESI-MS)-based assay. PCA showed potent anti-HSV-2 activity compared with that of acyclovir, with EC 50 values of 0.92 and 1.43 µg∙mL -1 , respectively, and selectivity indices > 217 and > 140, respectively. For the first time, AEHS was shown to exert anti-urease inhibition activity, with an IC 50 value of 82.4 µg∙mL -1 . This, combined with its safety, could facilitate its use in practical applications as a natural urease inhibitor. Our results present Hibiscus sabdariffa L. and its bioactive compound PCA as potential therapeutic agents in the treatment of HSV-2 infection and the treatment of diseases caused by urease-producing bacteria.

Investigation of the Effect of Some Optically Active Imine Compounds on the Enzyme Activities of hCA-I and hCA-II under In Vitro Conditions: An Experimental and Theoretical Study.

PubMed

Tektas, Osman; Akkemik, Ebru; Baykara, Haci

2016-06-01

Inhibitors of carbonic anhydrase (hCA; EC 4.2.1.1) are used as medicines for many diseases. Therefore, they are very important. In this study, a known series of Schiff bases were synthesized and their effects on the activities of hCA-I and hCA-II, which are cytosolic isoenzymes of carbonic anhydrase, were investigated under in vitro conditions. The synthesized compounds (H1, H2, H3, and H4) were found to cause inhibition on enzyme activities of hCA-1 and hCA-II. IC50 values of H1, H2, H3, and H4 compounds were 140, 88, 201, and 271 μM for hCA-I enzyme activity and 134, 251, 79, and 604 μM for hCA-II enzyme activity, respectively. The synthesized Schiff bases were characterized by several methods, including (1) H NMR, FT-IR, elemental analysis, and polarimetric measurements. Correlation coefficient square values (R(2) ) of comparison of the theoretical and experimental (1) H NMR shifts for H1, H2, H3, and H4 compounds were found as 0.9781, 0.9814, 0.9758, and 0.8635, respectively. © 2016 Wiley Periodicals, Inc.

New fluoroprostaglandin F(2alpha) derivatives with prostanoid FP-receptor agonistic activity as potent ocular-hypotensive agents.

PubMed

Nakajima, Tadashi; Matsugi, Takeshi; Goto, Wakana; Kageyama, Masaaki; Mori, Nobuaki; Matsumura, Yasushi; Hara, Hideaki

2003-12-01

To find new prostanoid FP-receptor agonists possessing potent ocular-hypotensive effects with minimal side effects, we evaluated the agonistic activities of newly synthesized prostaglandin F(2alpha) derivatives for the prostanoid FP-receptor both in vitro and in vivo. The iris constrictions induced by the derivatives and their effects on melanin content were examined using cat isolated iris sphincters and cultured B16 melanoma cells, respectively. The effects of derivative ester forms on miosis and intraocular pressure (IOP) were evaluated in cats and cynomolgus monkeys, respectively. Of these derivatives, 6 out of 12 compounds were more potent iris constrictors, with EC(50) values of 0.6 to 9.4 nM, than a carboxylic acid of latanoprost (EC(50)=13.6 nM). A carboxylic acid of latanoprost (100 microM) significantly increased the melanin content of cultured B16 melanoma cells, but some 15,15-difluoro derivatives, such as AFP-157 and AFP-172, did not. Topically applied AFP-168, AFP-169 and AFP-175 (isopropyl ester, methyl ester and ethyl ester forms, respectively, of AFP-172) induced miosis in cats more potently than latanoprost. AFP-168 (0.0005%) reduced IOP to the same extent as 0.005% latanoprost (for at least 8 h). These findings indicate that 15,15-difluoroprostaglandin F(2alpha) derivatives, especially AFP-168, have more potent prostanoid FP-receptor agonistic activities than latanoprost. Hence, AFP-168 may be worthy of further evaluation as an ocular-hypotensive agent.

Expected values for pedometer-determined physical activity in older populations

PubMed Central

2009-01-01

The purpose of this review is to update expected values for pedometer-determined physical activity in free-living healthy older populations. A search of the literature published since 2001 began with a keyword (pedometer, "step counter," "step activity monitor" or "accelerometer AND steps/day") search of PubMed, Cumulative Index to Nursing & Allied Health Literature (CINAHL), SportDiscus, and PsychInfo. An iterative process was then undertaken to abstract and verify studies of pedometer-determined physical activity (captured in terms of steps taken; distance only was not accepted) in free-living adult populations described as ≥ 50 years of age (studies that included samples which spanned this threshold were not included unless they provided at least some appropriately age-stratified data) and not specifically recruited based on any chronic disease or disability. We identified 28 studies representing at least 1,343 males and 3,098 females ranging in age from 50–94 years. Eighteen (or 64%) of the studies clearly identified using a Yamax pedometer model. Monitoring frames ranged from 3 days to 1 year; the modal length of time was 7 days (17 studies, or 61%). Mean pedometer-determined physical activity ranged from 2,015 steps/day to 8,938 steps/day. In those studies reporting such data, consistent patterns emerged: males generally took more steps/day than similarly aged females, steps/day decreased across study-specific age groupings, and BMI-defined normal weight individuals took more steps/day than overweight/obese older adults. The range of 2,000–9,000 steps/day likely reflects the true variability of physical activity behaviors in older populations. More explicit patterns, for example sex- and age-specific relationships, remain to be informed by future research endeavors. PMID:19706192

Small-molecule activators of TMEM16A, a calcium-activated chloride channel, stimulate epithelial chloride secretion and intestinal contraction

PubMed Central

Namkung, Wan; Yao, Zhen; Finkbeiner, Walter E.; Verkman, A. S.

2011-01-01

TMEM16A (ANO1) is a calcium-activated chloride channel (CaCC) expressed in secretory epithelia, smooth muscle, and other tissues. Cell-based functional screening of ∼110,000 compounds revealed compounds that activated TMEM16A CaCC conductance without increasing cytoplasmic Ca2+. By patch-clamp, N-aroylaminothiazole “activators” (Eact) strongly increased Cl− current at 0 Ca2+, whereas tetrazolylbenzamide “potentiators” (Fact) were not active at 0 Ca2+ but reduced the EC50 for Ca2+-dependent TMEM16A activation. Of 682 analogs tested, the most potent activator (Eact) and potentiator (Fact) produced large and more sustained CaCC Cl− currents than general agonists of Ca2+ signaling, with EC50 3–6 μM and Cl− conductance comparable to that induced transiently by Ca2+-elevating purinergic agonists. Analogs of activators were identified that fully inhibited TMEM16A Cl− conductance, providing further evidence for direct TMEM16A binding. The TMEM16A activators increased CaCC conductance in human salivary and airway submucosal gland epithelial cells, and IL-4 treated bronchial cells, and stimulated submucosal gland secretion in human bronchi and smooth muscle contraction in mouse intestine. Small-molecule, TMEM16A-targeted activators may be useful for drug therapy of cystic fibrosis, dry mouth, and gastrointestinal hypomotility disorders, and for pharmacological dissection of TMEM16A function.—Namkung, W., Yao, Z., Finkbeiner, W. E., Verkman, A. S. Small-molecule activators of TMEM16A, a calcium-activated chloride channel, stimulate epithelial chloride secretion and intestinal contraction. PMID:21836025

Exploration of the anti-enterovirus activity of a series of pleconaril/pirodavir-like compounds.

PubMed

Bernard, Angela; Lacroix, Céline; Cabiddu, Maria G; Neyts, Johan; Leyssen, Pieter; Pompei, Raffaello

2015-04-01

The Enterovirus genus of the Picornaviridae is represented by several viral pathogens that are associated with human disease, namely Poliovirus 1, Enterovirus 71 and Rhinoviruses. Enterovirus 71 has been associated with encephalitis, while Rhinoviruses are a major cause of asthma exacerbations and chronic obstructive pulmonary disease. Based on the structure of both pleconaril and pirodavir, we previously synthesized some original compounds as potential inhibitors of Rhinovirus replication. These compounds were explored for in vitro antiviral potential on other human pathogenic Enteroviruses, namely Enterovirus 71 on rhabdo-myosarcoma cells, Coxsackievirus B3 on Vero cells, Poliovirus 1 and Echovirus 11 on BGM cells. Activity was confirmed for compound against Rhinovirus 14. Furthermore, few compounds showed a cell-protective effect on Enterovirus 71, presented a marked improvement as compared to the reference drug pleconaril for inhibitory activity on both Enterovirus 71 and Poliovirus 1. The most striking observation was the clear cell protective effect for the set of analogues in a virus-cell-based assay for Echovirus 11 with an effective concentration (EC50) as low as 0.3 µM (Selectivity index or SI = 483), and selectivity indexes greater than 857 (EC50 = 0.6 µM) and 1524 (EC50 = 0.33 µM). Some of the evaluated compounds showed potent and selective antiviral activity against several enterovirus species, such as Enterovirus 71 (EV-A), Echovirus 11 (EV-B), and Poliovirus 1 (EV-C). This could be used as a starting point for the development of other pleconaril/pirodavir-like enterovirus inhibitors with broad-spectrum activity and improved effects as compared to the reference drugs. © The Author(s) 2015.

24 CFR 1000.50 - What Indian preference requirements apply to IHBG administration activities?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false What Indian preference requirements apply to IHBG administration activities? 1000.50 Section 1000.50 Housing and Urban Development... § 1000.50 What Indian preference requirements apply to IHBG administration activities? To the greatest...

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.

In Vitro inhibitory activity of Alpinia katsumadai extracts against influenza virus infection and hemagglutination

PubMed Central

2010-01-01

Background Alpinia katsumadai (AK) extracts and fractions were tested for in vitro antiviral activities against influenza virus type A, specially human A/PR/8/34 (H1N1) and avian A/Chicken/Korea/MS96/96 (H9N2), by means of time-of-addition experiments; pre-treatment, simultaneous treatment, and post treatment. Results In pre-treatment assay, the AK extracts and AK fractions did not show significant antiviral activity. During the simultaneous treatment assay, one AK extract and five AK fractions designated as AK-1 to AK-3, AK-5, AK-10, and AK-11 showed complete inhibition of virus infectivity against A/PR/8/34 (H1N1) and A/Chicken/Korea/MS96/96 (H9N2). The 50% effective inhibitory concentrations (EC50) of these one AK extracts and five AK fractions with exception of the AK-9 were from 0.8 ± 1.4 to 16.4 ± 4.5 μg/mL against A/PR/8/34 (H1N1). The two AK extracts and three AK fractions had EC50 values ranging from <0.39 ± 0.4 to 2.3 ± 3.6 μg/mL against A/Chicken/Korea/MS96/96 (H9N2). By the hemagglutination inhibition (HI) assay, the two AK extracts and five AK fractions completely inhibited viral adsorption onto chicken RBCs at less than 100 μg/mL against both A/PR/8/34 (H1N1) and A/Chicken/Korea/MS96/96 (H9N2). Interestingly, only AK-3 was found with inhibition for both viral attachment and viral replication after showing extended antiviral activity during the post treatment assay and quantitative real-time PCR. Conclusions These results suggest that AK extracts and fractions had strong anti-influenza virus activity that can inhibit viral attachment and/or viral replication, and may be used as viral prophylaxis. PMID:21062499

Acute toxicity of Corexit EC9500A and assessment of dioctyl sulfosuccinate as an indicator for monitoring four oil dispersants applied to diluted bitumen.

PubMed

MacInnis, Ceara Y; Brunswick, Pamela; Park, Grace H; Buday, Craig; Schroeder, Grant; Fieldhouse, Ben; Brown, Carl E; van Aggelen, Graham; Shang, Dayue

2018-05-01

The present study investigated oil dispersant toxicity to fish species typical of the cooler regions of Canada, together with less well-documented issues pertaining to oil dispersant monitoring. The oil dispersant toxicity of Corexit EC9500A was assessed for the freshwater fish species rainbow trout and the seawater species coho, chinook, and chum, with a final median lethal concentration (LC50) acute lethality range between 35.3 and 59.8 mg/L. The LC50 range was calculated using confirmed 0-h dispersant concentrations that were justified by fish mortality within the first 24 h of exposure and by variability of the dispersant indicator dioctyl sulfosuccinate (DOSS) used to monitor concentrations at later time points. To investigate DOSS as an oil dispersant indicator in the environment, microcosm systems were prepared containing Corexit EC9500A, Finasol OSR52, Slickgone NS, and Slickgone EW dispersants together with diluted bitumen. The DOSS indicator recovery was found to be stable for up to 13 d at 5 °C, 8 d at 10 °C, but significantly less than 8 d at ≥15 °C. After 3 d at temperatures ≥15 °C, the DOSS indicator recovery became less accurate and was dependent on multiple environmental factors including temperature, microbial activity, and aeration, with potential for loss of solvents and stabilizers. A final assessment determined DOSS to be a discrepant indicator for long-term monitoring of oil dispersant in seawater. Environ Toxicol Chem 2018;37:1309-1319. © 2018 SETAC. © 2018 SETAC.

Novel 384-well population patch clamp electrophysiology assays for Ca2+-activated K+ channels.

PubMed

John, Victoria H; Dale, Tim J; Hollands, Emma C; Chen, Mao Xiang; Partington, Leanne; Downie, David L; Meadows, Helen J; Trezise, Derek J

2007-02-01

Planar array electrophysiology techniques were applied to assays for modulators of recombinant hIK and hSK3 Ca2+-activated K+ channels. In CHO-hIK-expressing cells, under asymmetric K+ gradients, small-molecule channel activators evoked time- and voltage-independent currents characteristic of those previously described by classical patch clamp electrophysiology methods. In single-hole (cell) experiments, the large cell-to-cell heterogeneity in channel expression rendered it difficult to generate activator concentration-response curves. However, in population patch clamp mode, in which signals are averaged from up to 64 cells, well-to-well variation was substantially reduced such that concentration-response curves could be easily constructed. The absolute EC50 values and rank order of potency for a range of activators, including 1-EBIO and DC-EBIO, corresponded well with conventional patch clamp data. Activator responses of hIK and hSK3 channels could be fully and specifically blocked by the selective inhibitors TRAM-34 and apamin, with IC50 values of 0.31 microM and 3 nM, respectively. To demonstrate assay precision and robustness, a test set of 704 compounds was screened in a 384-well format of the hIK assay. All plates had Z' values greater than 0.6, and the statistical cutoff for activity was 8%. Eleven hits (1.6%) were identified from this set, in addition to the randomly spiked wells with known activators. Overall, our findings demonstrate that population patch clamp is a powerful and enabling method for screening Ca2+-activated K+ channels and provides significant advantages over single-cell electrophysiology (IonWorks(HT)) and other previously published approaches. Moreover, this work demonstrates for the 1st time the utility of population patch clamp for ion channel activator assays and for non-voltage-gated ion channels.

50 CFR 300.206 - Alternative procedures for IUU fishing activities.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 11 2012-10-01 2012-10-01 false Alternative procedures for IUU fishing activities. 300.206 Section 300.206 Wildlife and Fisheries INTERNATIONAL FISHING AND RELATED ACTIVITIES... for IUU fishing activities. (a) These certification procedures may be applied to fish or fish products...

Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8.

PubMed

De Petrocellis, Luciano; Vellani, Vittorio; Schiano-Moriello, Aniello; Marini, Pietro; Magherini, Pier Cosimo; Orlando, Pierangelo; Di Marzo, Vincenzo

2008-06-01

The plant cannabinoids (phytocannabinoids), cannabidiol (CBD), and Delta(9)-tetrahydrocannabinol (THC) were previously shown to activate transient receptor potential channels of both vanilloid type 1 (TRPV1) and ankyrin type 1 (TRPA1), respectively. Furthermore, the endocannabinoid anandamide is known to activate TRPV1 and was recently found to antagonize the menthol- and icilin-sensitive transient receptor potential channels of melastatin type 8 (TRPM8). In this study, we investigated the effects of six phytocannabinoids [i.e., CBD, THC, CBD acid, THC acid, cannabichromene (CBC), and cannabigerol (CBG)] on TRPA1- and TRPM8-mediated increase in intracellular Ca2+ in either HEK-293 cells overexpressing the two channels or rat dorsal root ganglia (DRG) sensory neurons. All of the compounds tested induced TRPA1-mediated Ca2+ elevation in HEK-293 cells with efficacy comparable with that of mustard oil isothiocyanates (MO), the most potent being CBC (EC(50) = 60 nM) and the least potent being CBG and CBD acid (EC(50) = 3.4-12.0 microM). CBC also activated MO-sensitive DRG neurons, although with lower potency (EC(50) = 34.3 microM). Furthermore, although none of the compounds tested activated TRPM8-mediated Ca2+ elevation in HEK-293 cells, they all, with the exception of CBC, antagonized this response when it was induced by either menthol or icilin. CBD, CBG, THC, and THC acid were equipotent (IC(50) = 70-160 nM), whereas CBD acid was the least potent compound (IC(50) = 0.9-1.6 microM). CBG inhibited Ca2+ elevation also in icilin-sensitive DRG neurons with potency (IC(50) = 4.5 microM) similar to that of anandamide (IC(50) = 10 microM). Our findings suggest that phytocannabinoids and cannabis extracts exert some of their pharmacological actions also by interacting with TRPA1 and TRPM8 channels, with potential implications for the treatment of pain and cancer.

Crystallographic snapshots of active site metal shift in E. coli fructose 1,6-bisphosphate aldolase.

PubMed

Tran, Huyen-Thi; Lee, Seon-Hwa; Ho, Thien-Hoang; Hong, Seung-Hye; Huynh, Kim-Hung; Ahn, Yeh-Jin; Oh, Deok-Kun; Kang, Lin-Woo

2016-12-01

Fructose 1,6-bisphosphate aldolase (FBA) is important for both glycolysis and gluconeogenesis in life. Class II (zinc dependent) FBA is an attractive target for the development of antibiotics against protozoa, bacteria, and fungi, and is also widely used to produce various high-value stereoisomers in the chemical and pharmaceutical industry. In this study, the crystal structures of class II Escherichia coli FBA (EcFBA) were determined from four different crystals, with resolutions between 1.8 Å and 2.0 Å. Native EcFBA structures showed two separate sites of Zn1 (interior position) and Zn2 (active site surface position) for Zn2＋ ion. Citrate and TRIS bound EcFBA structures showed Zn2＋ position exclusively at Zn2. Crystallographic snapshots of EcFBA structures with and without ligand binding proposed the rationale of metal shift at the active site, which might be a hidden mechanism to keep the trace metal cofactor Zn2＋ within EcFBA without losing it. [BMB Reports 2016; 49(12): 681-686].

MSFC Sortie Laboratory Environmental Control System (ECS) phase B design study results

NASA Technical Reports Server (NTRS)

Ignatonis, A. J.; Mitchell, K. L.

1974-01-01

Phase B effort of the Sortie Lab program has concluded. Results of that effort are presented which pertain to the definitions of the environmental control system (ECS). Numerous design studies were performed in Phase B to investigate system feasibility, complexity, weight, and cost. The results and methods employed for these design studies are included. An autonomous Sortie Lab ECS was developed which utilizes a deployed space radiator. Total system weight was projected to be 1814.4 kg including the radiator and fluids. ECS power requirements were estimated at 950 watts.

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.

50 CFR Figure 10 to Part 223 - Flounder TED

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 10 2012-10-01 2012-10-01 false Flounder TED 10 Figure 10 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 10 Figure 10 to Part 223—Flounder TED EC01JY91.056 ...

50 CFR Figure 10 to Part 223 - Flounder TED

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 10 2014-10-01 2014-10-01 false Flounder TED 10 Figure 10 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 10 Figure 10 to Part 223—Flounder TED EC01JY91.056 ...

50 CFR Figure 10 to Part 223 - Flounder TED

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 10 2013-10-01 2013-10-01 false Flounder TED 10 Figure 10 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 10 Figure 10 to Part 223—Flounder TED EC01JY91.056 ...

50 CFR 216.211 - Specified activity and specified geographical region.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 9 2011-10-01 2011-10-01 false Specified activity and specified... Activities Conducted During Offshore Structure Removal Operations on the Outer Continental Shelf in the U.S. Gulf of Mexico § 216.211 Specified activity and specified geographical region. (a) Regulations in this...

50 CFR 216.211 - Specified activity and specified geographical region.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Specified activity and specified... Activities Conducted During Offshore Structure Removal Operations on the Outer Continental Shelf in the U.S. Gulf of Mexico § 216.211 Specified activity and specified geographical region. (a) Regulations in this...

Tetracycline residues in royal jelly and honey by liquid chromatography tandem mass spectrometry: validation study according to Commission Decision 2002/657/EC.

PubMed

Giannetti, L; Longo, F; Buiarelli, F; Russo, M V; Neri, B

2010-09-01

A specific, sensitive and robust liquid chromatography tandem mass spectrometry method for determining oxytetracycline, tetracycline, chlortetracycline and doxycycline in royal jelly and honey samples is presented. Extraction of drug residues was performed by ammonium acetate buffer as extractant followed by a clean-up with metal chelate affinity chromatography and solid-phase extraction. Tetracycline analysis was performed using liquid chromatography-electrospray ionisation-tandem mass spectrometry. The presented method is the first validated for royal jelly and in accordance with the requirements set by Commission Decision 2002/657/EC. Recoveries of the methods, calculated spiking the samples at 5.0, 10.0, 20.0 and 30.0 μg kg(-1), were 79% to 90% for honey and 77% to 90% for royal jelly. The intra-day precision (RSD) ranged between 8.1% and 15.0% for honey and from 9.1% to 16.3% for royal jelly, while inter-day precision values were from 10.2% to 17.6% and from 10.6% to 18.4% respectively for honey and royal jelly. Linearity for the four analytes was calculated from 5.0 to 50.0 μg kg(-1). The decision limits (CCα) ranged from 6.2 to 6.4 μg kg(-1) and from 6.1 to 6.5 μg kg(-1) for honey and royal jelly, respectively. Detection capabilities values (CCβ) ranged between 7.2 and 7.7 μg kg(-1) and from 7.3 to 7.9 μg kg(-1) respectively for honey and royal jelly. The developed method is currently in use for confirmation of the official control analysis of honey and royal jelly samples.

Reliability of the ecSatter Inventory as a tool to measure eating competence.

PubMed

Stotts, Jodi L; Lohse, Barbara

2007-01-01

To examine the reliability of the ecSatter Inventory (ecSI), a measure of eating competence. Self-report questionnaires were administered in person or by mail. Retesting occurred 2 to 6 weeks after completion of the first questionnaire. Both administrations of the questionnaire were completed by 259 participants who were mostly food secure, white females with some college education; mean age was 26.9 +/- 10.4 years. Test-retest reliability and internal consistency. Spearman's rank correlation coefficients to estimate test-retest reliability and Cronbach alpha coefficients to estimate internal consistency. Spearman's rank correlation coefficient for ecSI total score was 0.68; subscale coefficients were 0.70 for eating attitudes, 0.70 for contextual skills, 0.65 for food acceptance, and 0.52 for internal regulation. Cronbach alpha coefficient for ecSI total score was 0.77. Subscale alphas coefficients were 0.80 for eating attitudes, 0.69 for contextual skills, 0.68 for food acceptance, and 0.66 for internal regulation. This study provides psychometric evidence about the reliability of ecSI as a measure of eating competence in this sample. Although some ecSI items may require revision, results suggest that the instrument may be used to evaluate nutrition education designed to improve eating competence.