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Sample records for ra active metabolite

  1. RaMP: A Comprehensive Relational Database of Metabolomics Pathways for Pathway Enrichment Analysis of Genes and Metabolites.

    Science.gov (United States)

    Zhang, Bofei; Hu, Senyang; Baskin, Elizabeth; Patt, Andrew; Siddiqui, Jalal K; Mathé, Ewy A

    2018-02-22

    The value of metabolomics in translational research is undeniable, and metabolomics data are increasingly generated in large cohorts. The functional interpretation of disease-associated metabolites though is difficult, and the biological mechanisms that underlie cell type or disease-specific metabolomics profiles are oftentimes unknown. To help fully exploit metabolomics data and to aid in its interpretation, analysis of metabolomics data with other complementary omics data, including transcriptomics, is helpful. To facilitate such analyses at a pathway level, we have developed RaMP (Relational database of Metabolomics Pathways), which combines biological pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, WikiPathways, and the Human Metabolome DataBase (HMDB). To the best of our knowledge, an off-the-shelf, public database that maps genes and metabolites to biochemical/disease pathways and can readily be integrated into other existing software is currently lacking. For consistent and comprehensive analysis, RaMP enables batch and complex queries (e.g., list all metabolites involved in glycolysis and lung cancer), can readily be integrated into pathway analysis tools, and supports pathway overrepresentation analysis given a list of genes and/or metabolites of interest. For usability, we have developed a RaMP R package (https://github.com/Mathelab/RaMP-DB), including a user-friendly RShiny web application, that supports basic simple and batch queries, pathway overrepresentation analysis given a list of genes or metabolites of interest, and network visualization of gene-metabolite relationships. The package also includes the raw database file (mysql dump), thereby providing a stand-alone downloadable framework for public use and integration with other tools. In addition, the Python code needed to recreate the database on another system is also publicly available (https://github.com/Mathelab/RaMP-BackEnd). Updates for databases in RaMP will be

  2. 226Ra adsorption on active coals from waste waters

    International Nuclear Information System (INIS)

    Panturu, E.; Georgescu, D.P.; Serban, N.; Filip, D.; Radulescu, R.

    2000-01-01

    During the mining and extraction of uranium, the principle means of protection measurement is to prevent uranium and its products diffusing into the environment. The main carriers of radioactive elements in the environment are air and water. Therefore, reduction of the pollution at a uranium mine can be achieved by the treatment of waste waters contaminated with 226 Ra Radium contaminated waste waters represent a major biological risk. This paper presents the results of the study of the sorption of 226 Ra on active coal mechanisme and the influence of the physical and chemical characteristics of fluid. The 226 Ra removal from the residue pond water at the uranium ore processing plant was studied using eight types of indigenous active coals. The experimental results for each type of active coal and their effect on removal of 226 Ra from waste waters are presented in this paper. (author)

  3. Concentrations and activity ratios of 228Ra and 226Ra in surface seawater along the Pacific coast of Japan

    International Nuclear Information System (INIS)

    Ohta, T.; Mahara, Y.; Kubota, T.; Sato, J.; Gamo, T.

    2011-01-01

    We measured the 228 Ra/ 226 Ra activity ratios in surface seawater along the Pacific coast of Japan at five ports around the island of Izu-Oshima (n = 29), at Atami in Sagami Bay (n = 13), and at Umizuri Park in Tokyo Bay (n = 14). We also conducted these measurements along a transect from the open Pacific Ocean across the Kuroshio to the mouth of Tokyo Bay (n = 7). The activity ratios decreased with increasing salinity of the sampling sites. The 228 Ra/ 226 Ra activity ratios in surface seawater along the coast gradually decreased after at the end of autumn and were lowest in winter and the beginning of spring. The surface salinity along the coast decreased from summer into autumn and increased from winter to the beginning of spring. The activity ratios decreased with the increase of salinity. The variation in activity ratios at the three coastal sites is possibly caused by differing contributions of surface seawater from the Kuroshio and surrounding open ocean. The different patterns and ranges of variation in the 228 Ra/ 226 Ra activity ratios in surface seawater at Izu-Oshima, Atami, and Umizuri Park may reflect both the amount of water from the Kuroshio and vicinity, and the local bathymetry, because continental shelf sediment is the source of Ra isotopes in surface seawater. (orig.)

  4. 226Ra and 228Ra activities associated with agricultural drainage ponds and wetland ponds in the Kankakee Watershed, Illinois-Indiana, USA

    International Nuclear Information System (INIS)

    Sidle, W.C.; Shanklin, D.; Lee, P.Y.; Roose, D.L.

    2001-01-01

    Background radioactivity is elevated in many agricultural drainage ponds and also constructed wetland ponds in the Kankakee watershed. During 1995-1999, gross-α and -β activities were measured up to 455 and 1650 mBq L -1 , respectively. 226 Ra and 228 Ra averaged 139 and 192 mBq L -1 in controlled drainage ponds compared to 53 and 58 mBq L -1 for 226 Ra and 228 Ra, respectively, in native wetland ponds. Analyses of applied ammonium phosphate fertilizers near both native and controlled ponds indicate comparable 226 Ra/ 228 Ra and 228 Ra/ 232 Th activity ratios with only the surface waters in the controlled ponds. For example, 226 Ra/ 228 Ra activity ratios in controlled ponds ranged from 0.79 to 0.91 and group with a local fertilizer batch containing FL phosphate compounds with 226 Ra/ 228 Ra activity ratios of 0.83-1.04. Local soils of the Kankakee watershed have 226 Ra/ 228 Ra activity ratios of 0.54-0.70. Calculated Ra fluxes of waters, in drainage ditches associated with these controlled ponds, for 226 Ra ranged from 0.77 to 9.00 mBq cm -2 d -1 and for 228 Ra ranged from 1.22 to 8.43 mBq cm -2 d -1 . Ra activity gradients were measured beneath these controlled ponds both in agricultural landscapes and in constructed wetlands, all being associated with drainage ditches. Ra had infiltrated to the local water table but was below regulatory maximum contaminant limits. Still, measurable Ra activity was measured downgradient of even the constructed wetlands in the Kankakee watershed, suggesting that the attenuation of Ra was low. However, no Ra excess was observed in the riparian zone or the Kankakee River downgradient of the native wetland ponds

  5. Pharmaceutically active secondary metabolites of marine actinobacteria.

    Science.gov (United States)

    Manivasagan, Panchanathan; Venkatesan, Jayachandran; Sivakumar, Kannan; Kim, Se-Kwon

    2014-04-01

    Marine actinobacteria are one of the most efficient groups of secondary metabolite producers and are very important from an industrial point of view. Many representatives of the order Actinomycetales are prolific producers of thousands of biologically active secondary metabolites. Actinobacteria from terrestrial sources have been studied and screened since the 1950s, for many important antibiotics, anticancer, antitumor and immunosuppressive agents. However, frequent rediscovery of the same compounds from the terrestrial actinobacteria has made them less attractive for screening programs in the recent years. At the same time, actinobacteria isolated from the marine environment have currently received considerable attention due to the structural diversity and unique biological activities of their secondary metabolites. They are efficient producers of new secondary metabolites that show a range of biological activities including antibacterial, antifungal, anticancer, antitumor, cytotoxic, cytostatic, anti-inflammatory, anti-parasitic, anti-malaria, antiviral, antioxidant, anti-angiogenesis, etc. In this review, an evaluation is made on the current status of research on marine actinobacteria yielding pharmaceutically active secondary metabolites. Bioactive compounds from marine actinobacteria possess distinct chemical structures that may form the basis for synthesis of new drugs that could be used to combat resistant pathogens. With the increasing advancement in science and technology, there would be a greater demand for new bioactive compounds synthesized by actinobacteria from various marine sources in future. Copyright © 2013 Elsevier GmbH. All rights reserved.

  6. Antimalarial Activity of Plant Metabolites.

    Science.gov (United States)

    Pan, Wen-Hui; Xu, Xin-Ya; Shi, Ni; Tsang, Siu Wai; Zhang, Hong-Jie

    2018-05-06

    Malaria, as a major global health problem, continues to affect a large number of people each year, especially those in developing countries. Effective drug discovery is still one of the main efforts to control malaria. As natural products are still considered as a key source for discovery and development of therapeutic agents, we have evaluated more than 2000 plant extracts against Plasmodium falciparum . As a result, we discovered dozens of plant leads that displayed antimalarial activity. Our phytochemical study of some of these plant extracts led to the identification of several potent antimalarial compounds. The prior comprehensive review article entitled “Antimalarial activity of plant metabolites” by Schwikkard and Van Heerden (2002) reported structures of plant-derived compounds with antiplasmodial activity and covered literature up to the year 2000. As a continuation of this effort, the present review covers the antimalarial compounds isolated from plants, including marine plants, reported in the literature from 2001 to the end of 2017. During the span of the last 17 years, 175 antiplasmodial compounds were discovered from plants. These active compounds are organized in our review article according to their plant families. In addition, we also include ethnobotanical information of the antimalarial plants discussed.

  7. Antimalarial Activity of Plant Metabolites

    Directory of Open Access Journals (Sweden)

    Wen-Hui Pan

    2018-05-01

    Full Text Available Malaria, as a major global health problem, continues to affect a large number of people each year, especially those in developing countries. Effective drug discovery is still one of the main efforts to control malaria. As natural products are still considered as a key source for discovery and development of therapeutic agents, we have evaluated more than 2000 plant extracts against Plasmodium falciparum. As a result, we discovered dozens of plant leads that displayed antimalarial activity. Our phytochemical study of some of these plant extracts led to the identification of several potent antimalarial compounds. The prior comprehensive review article entitled “Antimalarial activity of plant metabolites” by Schwikkard and Van Heerden (2002 reported structures of plant-derived compounds with antiplasmodial activity and covered literature up to the year 2000. As a continuation of this effort, the present review covers the antimalarial compounds isolated from plants, including marine plants, reported in the literature from 2001 to the end of 2017. During the span of the last 17 years, 175 antiplasmodial compounds were discovered from plants. These active compounds are organized in our review article according to their plant families. In addition, we also include ethnobotanical information of the antimalarial plants discussed.

  8. Biologically Active Metabolites Synthesized by Microalgae

    Directory of Open Access Journals (Sweden)

    Michele Greque de Morais

    2015-01-01

    Full Text Available Microalgae are microorganisms that have different morphological, physiological, and genetic traits that confer the ability to produce different biologically active metabolites. Microalgal biotechnology has become a subject of study for various fields, due to the varied bioproducts that can be obtained from these microorganisms. When microalgal cultivation processes are better understood, microalgae can become an environmentally friendly and economically viable source of compounds of interest, because production can be optimized in a controlled culture. The bioactive compounds derived from microalgae have anti-inflammatory, antimicrobial, and antioxidant activities, among others. Furthermore, these microorganisms have the ability to promote health and reduce the risk of the development of degenerative diseases. In this context, the aim of this review is to discuss bioactive metabolites produced by microalgae for possible applications in the life sciences.

  9. Possibility of rapidly reporting 226Ra activity in 226Ra-222Rn samples with unknown equilibrium factor by γ spectrometer

    Institute of Scientific and Technical Information of China (English)

    SU Qiong; ZHENG Rui; CHEN Yong; CHENG Jian-Ping

    2004-01-01

    This paper reports the observed changes for equilibrium factors between 226Ra and 222Rn with sealing time of the samples. The samples include soil, raw coal, mineral water, cement, rock, etc. Especially the conceptions of "pre-equilibrium time" and "pre-equilibrium factor" have been put forward and methods of measuring and processing data have been given which can be used for rapidly reporting activity of 226Ra in samples with unknown equilibrium factor. It is definitely concluded that, using methods given in the paper, a test report will be completed in 3~7days, instead of one month, after receiving the sample whose activity is not lower than LLD of the spectrometer.

  10. Metabolic characteristics of 13-cis-retinoic acid (isotretinoin) and anti-tumour activity of the 13-cis-retinoic acid metabolite 4-oxo-13-cis-retinoic acid in neuroblastoma.

    Science.gov (United States)

    Sonawane, Poonam; Cho, Hwang Eui; Tagde, Ashujit; Verlekar, Dattesh; Yu, Alice L; Reynolds, C Patrick; Kang, Min H

    2014-12-01

    Isotretinoin (13-cis-retinoic acid; 13-cRA) is a differentiation inducer used to treat minimal residual disease after myeloablative therapy for high-risk neuroblastoma. However, more than 40% of children develop recurrent disease during or after 13-cRA treatment. The plasma concentrations of 13-cRA in earlier studies were considered subtherapeutic while 4-oxo-13-cis-RA (4-oxo-13-cRA), a metabolite of 13-cRA considered by some investigators as inactive, were greater than threefold higher than 13-cRA. We sought to define the metabolic pathways of 13-cRA and investigated the anti-tumour activity of its major metabolite, 4-oxo-13-cRA. Effects of 13-cRA and 4-oxo-13-cRA on human neuroblastoma cell lines were assessed by DIMSCAN and flow cytometry for cell proliferation, MYCN down-regulation by reverse transcription PCR and immunoblotting, and neurite outgrowth by confocal microscopy. 13-cRA metabolism was determined using tandem MS in human liver microsomes and in patient samples. Six major metabolites of 13-cRA were identified in patient samples. Of these, 4-oxo-13-cRA was the most abundant, and 4-oxo-13-cRA glucuronide was also detected at a higher level in patients. CYP3A4 was shown to play a major role in catalysing 13-cRA to 4-oxo-13-cRA. In human neuroblastoma cell lines, 4-oxo-13-cRA and 13-cRA were equi-effective at inducing neurite outgrowth, inhibiting proliferation, decreasing MYCN mRNA and protein, and increasing the expression of retinoic acid receptor-β mRNA and protein levels. We showed that 4-oxo-13-cRA is as active as 13-cRA against neuroblastoma cell lines. Plasma levels of both 13-cRA and 4-oxo-13-cRA should be evaluated in pharmacokinetic studies of isotretinoin in neuroblastoma. © 2014 The British Pharmacological Society.

  11. Relative activities of 212Bi (thorium-C) and 228Ra (mesothorium-1) in former radium dial workers

    International Nuclear Information System (INIS)

    Keane, A.T.; Essling, M.A.; Lucas, H.F.

    1984-01-01

    From analyses of bones, estimates were made of the relative intakes of 228 Ra and 226 Ra by the employees of a dial-painting studio that used luminous compounds activated with technical mesothorium. These data, in turn, were used to derive estimates of 228 Ra activity from activities of 226 Ra in living colleagues whose body contents of 226 Ra and 212 Bi had been measured. The indirectly determined 212 Bi to 228 Ra activity ratios in the living workers averaged 1.56 +- 0.10 (S.E.) at a median of 42 yr post intake. If no 228 Ra decay products are excreted, the expected 212 Bi to 228 Ra activity ratio at 42 yr after intake is 1.59 according to the simple power function of radium retention of Norris et al., and 1.72 according to the alkaline earth model of ICRP No. 20. 15 references, 2 tables

  12. Metabolites of alectinib in human: their identification and pharmacological activity

    Directory of Open Access Journals (Sweden)

    Mika Sato-Nakai

    2017-07-01

    Full Text Available Two metabolites (M4 and M1b in plasma and four metabolites (M4, M6, M1a and M1b in faeces were detected through the human ADME study following a single oral administration of [14C]alectinib, a small-molecule anaplastic lymphoma kinase inhibitor, to healthy subjects. In the present study, M1a and M1b, which chemical structures had not been identified prior to the human ADME study, were identified as isomers of a carboxylate metabolite oxidatively cleaved at the morpholine ring. In faeces, M4 and M1b were the main metabolites, which shows that the biotransformation to M4 and M1b represents two main metabolic pathways for alectinib. In plasma, M4 was a major metabolite and M1b was a minor metabolite. The contribution to in vivo pharmacological activity of these circulating metabolites was assessed from their in vitro pharmacological activity and plasma protein binding. M4 had a similar cancer cell growth inhibitory activity and plasma protein binding to that of alectinib, suggesting its contribution to the antitumor activity of alectinib, whereas the pharmacological activity of M1b was insignificant.

  13. Antibacterial activity of secondary metabolites isolated from ...

    African Journals Online (AJOL)

    Aghomotsegin

    2015-10-28

    Oct 28, 2015 ... Alternaria spp. are cosmopolitan mould fungi and can be found in soils ... the secondary metabolites products from A. alternata and ..... Zone of inhibition (mm) of test bacterial strains to fungal products and standard antibiotics. Fungal ... marine actinomycetes from pulicat, Muttukadu, and Ennore estuaries.

  14. Phosphoproteome and Transcriptome of RA-Responsive and RA-Resistant Breast Cancer Cell Lines.

    Directory of Open Access Journals (Sweden)

    Marilyn Carrier

    Full Text Available Retinoic acid (RA, the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Due to these properties, RA has proven anti-cancer capacity. Several breast cancer cells respond to the antiproliferative effects of RA, while others are RA-resistant. However, the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here, in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes, we compared two human breast cancer cell lines, a RA-responsive one, the MCF7 cell line, and a RA-resistant one, the BT474 cell line, which depicts several alterations of the "kinome". Using high-resolution nano-LC-LTQ-Orbitrap mass spectrometry associated to phosphopeptide enrichment, we found that several proteins involved in signaling and in transcription, are differentially phosphorylated before and after RA addition. The paradigm of these proteins is the RA receptor α (RARα, which was phosphorylated in MCF7 cells but not in BT474 cells after RA addition. The panel of the RA-regulated genes was also different. Overall our results indicate that RA resistance might correlate with the deregulation of the phosphoproteome with consequences on gene expression.

  15. Evaluation of the activity concentration of {sup 226}Ra, {sup 228}Ra and {sup 210}Pb in sediments from Antarctica in the Admiralty Bay region

    Energy Technology Data Exchange (ETDEWEB)

    Mora, Tamires de A.; Oliveira, Joselene de, E-mail: tamires.mora@usp.br, E-mail: jolivei@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Figueira, Rubens C.L.; Mahiques, Michel M.; Sousa, Silvia H.M., E-mail: rfigueira@usp.br, E-mail: mahiques@usp.br, E-mail: smsousa@usp.br [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Instituto Oceanografico

    2015-07-01

    In this study, we performed the radiochemical characterization of a sedimentary record (1B profile), collected in the vicinity of Admiralty Bay, King George Island in Antarctic Operation XXXI (January/2013). The activities of {sup 226}Ra, {sup 228}Ra and {sup 210}Pb were determined by the counting of gross alpha and gross beta activities in the precipitates of Ba(Ra)SO{sub 4} and PbCrO{sub 4}. Those measurements were carried out in a low background gas flow proportional detector. The {sup 226}Ra and {sup 228}Ra were measured after 21 days of the final precipitation. The {sup 210}Pb activity was determined after 10 days of the precipitation date by gross beta counting of its {sup 210}Bi decay product. The activity concentration of {sup 226}Ra ranged from 11±1 (mBq g-1) to 54±3 (mBq g{sup -1}), and the {sup 228}Ra ranged from 48±5 (mBq g{sup -1}) to 155±16 (mBq g{sup -1}). The activity concentration of {sup 210}Pb varied from 8±1 (mBq g{sup -1}) to 458±46 (mBq g{sup -1}), while unsupported {sup 210}Pb ranged from 6±1 (mBq g{sup -1}) to 434±65 (mBq g{sup -1}). The {sup 210}Pb concentrations in sediments have often been used to dating events like deposition and accumulation in various marine environments. Taking into account the results of {sup 210}Pb and {sup 226}Ra activities obtained in testimony-1B it was estimated the unsupported {sup 210}Pb activity which was applied to the CIC geochronological dating model (Constant Initial Concentration). Based in these data, the sedimentation rate obtained was 0.63±0.02 cm year{sup -1}. (author)

  16. Evaluation of the activity concentration of 226Ra, 228Ra and 210Pb in sediments from Antarctica in the Admiralty Bay region

    International Nuclear Information System (INIS)

    Mora, Tamires de A.; Oliveira, Joselene de; Figueira, Rubens C.L.; Mahiques, Michel M.; Sousa, Silvia H.M.

    2015-01-01

    In this study, we performed the radiochemical characterization of a sedimentary record (1B profile), collected in the vicinity of Admiralty Bay, King George Island in Antarctic Operation XXXI (January/2013). The activities of 226 Ra, 228 Ra and 210 Pb were determined by the counting of gross alpha and gross beta activities in the precipitates of Ba(Ra)SO 4 and PbCrO 4 . Those measurements were carried out in a low background gas flow proportional detector. The 226 Ra and 228 Ra were measured after 21 days of the final precipitation. The 210 Pb activity was determined after 10 days of the precipitation date by gross beta counting of its 210 Bi decay product. The activity concentration of 226 Ra ranged from 11±1 (mBq g-1) to 54±3 (mBq g -1 ), and the 228 Ra ranged from 48±5 (mBq g -1 ) to 155±16 (mBq g -1 ). The activity concentration of 210 Pb varied from 8±1 (mBq g -1 ) to 458±46 (mBq g -1 ), while unsupported 210 Pb ranged from 6±1 (mBq g -1 ) to 434±65 (mBq g -1 ). The 210 Pb concentrations in sediments have often been used to dating events like deposition and accumulation in various marine environments. Taking into account the results of 210 Pb and 226 Ra activities obtained in testimony-1B it was estimated the unsupported 210 Pb activity which was applied to the CIC geochronological dating model (Constant Initial Concentration). Based in these data, the sedimentation rate obtained was 0.63±0.02 cm year -1 . (author)

  17. On alpha activity relationships in 226Ra and U/sub nat/

    International Nuclear Information System (INIS)

    Krejbichova, Z.

    1982-01-01

    A gross alpha activity of 0.1 Bq/l is permitted for drinking and surface waters. If gross activity is higher, it is suitable to determine the 226 Ra content which must not exceed 0.1 Bq/l. The permissible content of natural uranium is 0.05 mg/l. In most samples of ground and surface waters gross alpha activity was below the permissible limit. In some samples with a high content of salts a higher Ra+U activity was found which exceeded gross activity. This was caused by the interference of nonradioactive admixtures. In other samples a higher gross alpha activity was found than was the sum Ra+U which may have been caused by alpha sources from radon decay. It was found that the gross alpha activity of waters is rather caused by uranium than by radium. (E.S.)

  18. Translocator protein as an imaging marker of macrophage and stromal activation in RA pannus.

    Science.gov (United States)

    Narayan, Nehal; Owen, David; Mandhair, Harpreet; Smyth, Erica; Carlucci, Francesco; Saleem, Azeem; Gunn, Roger; Rabiner, Eugenii Ilan A; Wells, Lisa; Dakin, Stephanie; Sabokbar, Afsie; Taylor, Peter

    2018-01-04

    Positron Emission Tomography (PET) radioligands targeted to Translocator protein (TSPO), offer a highly sensitive and specific means of imaging joint inflammation in rheumatoid arthritis (RA). Through high expression of TSPO on activated macrophages, TSPO PET has been widely reported in several studies of RA as a means of imaging synovial macrophages in vivo. However, this premise does not take into account the ubiquitous expression of TSPO. This study aimed to investigate TSPO expression in major cellular constituents of RA pannus; monocytes, macrophages, fibroblast-like synoviocytes (FLS) and CD4+ T lymphocytes, to more accurately interpret TSPO PET signal from RA synovium. Methods: 3 RA patients and 3 healthy volunteers underwent PET both knees using the TSPO radioligand 11 C-PBR28. Through synovial tissue 3H-PBR28 autoradiography and immunostaining of 6 RA patients and 6 healthy volunteers, cellular expression of TSPO in synovial tissue was evaluated. TSPO mRNA expression and 3H-PBR28 radioligand binding was assessed using in vitro monocytes, macrophages, FLS and CD4+ T-lymphocytes. Results: 11 C-PBR28 PET signal was significantly higher in RA compared to healthy joints (average SUV 0.82± 0.12 compared to 0.03± 0.004 respectively, p<0.01). Further, 3H-PBR28 specific binding in synovial tissue was approximately 10-fold higher in RA compared to healthy controls. Immunofluorescence revealed TSPO expression on macrophages, FLS and CD4+ T cells. In vitro study demonstrated highest TSPO mRNA expression and 3H-PBR28 specific binding, in activated FLS, non-activated and activated 'M2' reparative macrophages, with least TSPO expression in activated and non-activated CD4+ T lymphocytes. Conclusion: This study is the first evaluation of cellular TSPO expression in synovium, finding highest TSPO expression and PBR28 binding on activated synovial FLS and M2 phenotype macrophages. TSPO targeted PET may therefore have unique sensitivity to detect FLS and macrophage

  19. Determining activity of 40K with disturbing from 228Ra by γ spectrometry

    International Nuclear Information System (INIS)

    Su Qiong

    1997-09-01

    The measurement methods and some viewpoints for processing data about determining activities in a reference material are reported (The Laboratory of Industrial Hygiene Ministry have a hand in the determining). The measurement and correct problems of determining activity of 40 K with disturbing from 228 Ra by γ spectrometry, which were neglected in the past a lot of measurement, are especially described. It is pointed out that if the correct is neglected then the value of 40 K in the current reference material, in that activities of both 22 '8Ra and 40 K are matched, will be determined with system error of about 20%. (14 refs., 3 tabs.)

  20. Activity concentrations of /sup 226/Ra, /sup 228/Ra, /sup 210/Pb, /sup 40/K and /sup 7/Be and their temporal variations in surface air

    Energy Technology Data Exchange (ETDEWEB)

    Hoetzl, H.; Winkler, R.

    1987-01-01

    Activity concentrations of the long-lived natural radionuclides /sup 226/Ra, /sup 228/Ra, /sup 210/Pb, /sup 40/K and of /sup 7/Be in surface air were measured twice monthly at a semi-rural location 10 km north of Munich (FRG) for at least three years. For the time interval 1983-1985, all values were found to be distributed log-normally, with geometric means (in ..mu..Bq m-./sup 3/) of 1.2 for /sup 226/Ra, 0.5 for /sup 228/Ra, 580 for /sup 210/Pb, 12 for /sup 40/K and 3500 for /sup 7/Be. Reflecting their common origin, the activity concentrations of /sup 226/Ra and /sup 40/K are correlated with surface air dust concentrations (geometric mean 59 ..mu..g m/sup -3/). Seasonal variations of /sup 210/Pb and /sup 7/Be air activity concentrations are established for the time interval 1978-1985.. The contribution of local soil activity to the air activity concentrations of these radionuclides and of natural uranium is discussed. Resuspension factors are found to be of the order of 10/sup -9/ m/sup -1/.

  1. A Review of the Secondary Metabolites and Biological Activities of ...

    African Journals Online (AJOL)

    Review Article. A Review of the Secondary Metabolites and Biological. Activities of Tinospora crispa ... triterpenes have been isolated, some of which have also shown corresponding biological activities. The current review is an update on the .... were found to exhibit higher antioxidative potency than the synthetic antioxidant.

  2. A Dual Key-Based Activation Scheme for Secure LoRaWAN

    Directory of Open Access Journals (Sweden)

    Jaehyu Kim

    2017-01-01

    Full Text Available With the advent of the Internet of Things (IoT era, we are experiencing rapid technological progress. Billions of devices are connected to each other, and our homes, cities, hospitals, and schools are getting smarter and smarter. However, to realize the IoT, several challenging issues such as connecting resource-constrained devices to the Internet must be resolved. Recently introduced Low Power Wide Area Network (LPWAN technologies have been devised to resolve this issue. Among many LPWAN candidates, the Long Range (LoRa is one of the most promising technologies. The Long Range Wide Area Network (LoRaWAN is a communication protocol for LoRa that provides basic security mechanisms. However, some security loopholes exist in LoRaWAN’s key update and session key generation. In this paper, we propose a dual key-based activation scheme for LoRaWAN. It resolves the problem of key updates not being fully supported. In addition, our scheme facilitates each layer in generating its own session key directly, which ensures the independence of all layers. Real-world experimental results compared with the original scheme show that the proposed scheme is totally feasible in terms of delay and battery consumption.

  3. Determination of specific activities of U-238, Ra-226, Ra-228 e Th-228 in samples of mineral fertilizers with phosphorus

    International Nuclear Information System (INIS)

    Garcez, R.W.D.; Lopes, J.M.; Silva, A.X. da

    2016-01-01

    Samples were analyzed by gamma spectrometry mineral fertilizers with the HPGe detector and aid LabSOCS software for calculating the detection efficiency curve. Specific activities found for Pa-234m, Ra-226, Ra-228 and Th-228 in samples of phosphate fertilizers were 505 Bq.kg"-"1, 458 Bq.kg"-"1, 450 Bq.kg"-"1 and 394 Bq.kg"-"1, respectively. And for the NPK fertilizer samples were found average values of 390 Bq.kg"-"1, 252 Bq.kg"-"1, 280 Bq.kg"-"1 and 268 Bq.kg"-"1, respectively. (author)

  4. Factors associated with absenteeism, presenteeism and activity impairment in patients in the first years of RA.

    Science.gov (United States)

    Bansback, Nick; Zhang, Wei; Walsh, David; Kiely, Patrick; Williams, Richard; Guh, Daphne; Anis, Aslam; Young, Adam

    2012-02-01

    To understand the impact of the early years of RA on all aspects of work productivity, and determine how this is related to clinical markers. Previous research on work productivity has examined predominantly early retirement and absenteeism. The impact of reduced work performance (presenteeism) and activity impairment is less well understood in early RA populations. Working patients enrolled in an RA inception cohort were recruited into a nested study. A questionnaire incorporating the Work Productivity and Activity Impairment (WPAI) instrument was administered with a number of clinical outcomes, including the Multidimensional Health Assessment Questionnaire (MD-HAQ) and scales for pain, fatigue and patient assessment of disease patient global assessment (PtGA). Analysis included 150 RA patients, with the mean age at onset being 48 years (s.d. 10 years) and disease duration from symptom onset being 49 months. Patients had relatively mild disease: MD-HAQ (0.6), pain (3.6), PtGA (3.6) and fatigue (4.6). Of the 92% patients working for pay, 19% reported missing work (absenteeism) in the past week due to their health, accounting for 46% of their working time. Even while at work, ∼25% of actual hours was lost due to poor health, while outside work 33% of patients' regular daily activities were prevented. In multivariate analyses, disease severity was associated with the presence of absenteeism, presenteeism and activity impairment. Patients able to self-schedule their work had lower presenteeism and activity impairment. Productivity loss is common in patients in the first years of RA who are in paid work and was associated with work characteristics and adverse clinical outcomes.

  5. Evaluation of the activity concentration of 226Ra, 228Ra and 210Pb in sediments from Antarctica in the Admiralty bay region

    International Nuclear Information System (INIS)

    Mora, Tamires de Araujo

    2015-01-01

    The natural radionuclides from radioactive series of 238 U, 235 U and 232 Th have been applied as tracers in environmental studies for understanding the dynamics that occur in both marine and terrestrial environment, as for example, in research of oceanic processes and management of the coastal region. In the marine environment, these radionuclides can be used to estimate biogeochemical fluxes of marine particles and nutrients that occur in the water column as well as in the sediment. Several research works applied the distribution and the respective disequilibrium degree of natural radionuclides in the environment, including geochronological models for obtaining historical information on samples of certain sediment profile. In this study we performed a radiochemical characterization of the distribution of 226 Ra, 228 Ra and 210 Pb from a sedimentary column called 1B (248 cm long) collected in the Admiralty Bay, Antarctic Peninsula region. The methodology used included the acid leaching of sediment samples followed by the radiochemical sequential separation of 226 Ra and 228 Ra by co-precipitation with Ba(Ra)SO 4 and 210 Pb by co-precipitation with PbCrO 4 . All measurements were carried out by counting of gross alpha and gross beta measures in a low background gas flow proportional detector. The activity concentrations of 226 Ra and 210 Pb were used to estimate the unsupported 210 Pb activities present in sediment profile 1 B. Based on unsupported 210 Pb data and the application of the CIC model (Constant Initial Concentration), it was possible to determine the sedimentation rate of 0.59 ± 0.05 cm /year. (author)

  6. Gender, body mass index and rheumatoid arthritis disease activity: results from the QUEST-RA Study.

    Science.gov (United States)

    Jawaheer, D; Olsen, J; Lahiff, M; Forsberg, S; Lähteenmäki, J; da Silveira, I G; Rocha, F A; Magalhães Laurindo, I M; Henrique da Mota, L M; Drosos, A A; Murphy, E; Sheehy, C; Quirke, E; Cutolo, M; Rexhepi, S; Dadoniene, J; Verstappen, S M M; Sokka, T

    2010-01-01

    To investigate whether body mass index (BMI), as a proxy for body fat, influences rheumatoid arthritis (RA) disease activity in a gender-specific manner. Consecutive patients with RA were enrolled from 25 countries into the QUEST-RA program between 2005 and 2008. Clinical and demographic data were collected by treating rheumatologists and by patient self-report. Distributions of Disease Activity Scores (DAS28), BMI, age, and disease duration were assessed for each country and for the entire dataset; mean values between genders were compared using Student's t-tests. An association between BMI and DAS28 was investigated using linear regression, adjusting for age, disease duration and country. A total of 5,161 RA patients (4,082 women and 1,079 men) were included in the analyses. Overall, women were younger, had longer disease duration, and higher DAS28 scores than men, but BMI was similar between genders. The mean DAS28 scores increased with increasing BMI from normal to overweight and obese, among women, whereas the opposite trend was observed among men. Regression results showed BMI (continuous or categorical) to be associated with DAS28. Compared to the normal BMI range, being obese was associated with a larger difference in mean DAS28 (0.23, 95% CI: 0.11, 0.34) than being overweight (0.12, 95% CI: 0.03, 0.21); being underweight was not associated with disease activity. These associations were more pronounced among women, and were not explained by any single component of the DAS28. BMI appears to be associated with RA disease activity in women, but not in men.

  7. Secondary Metabolites from Inula britannica L. and Their Biological Activities

    Directory of Open Access Journals (Sweden)

    Yoon-Ha Kim

    2010-03-01

    Full Text Available Inula britannica L., family Asteraceae, is used in traditional Chinese and Kampo Medicines for various diseases. Flowers or the aerial parts are a rich source of secondary metabolites. These consist mainly of terpenoids (sesquiterpene lactones and dimmers, diterpenes and triterpenoids and flavonoids. The isolated compounds have shown diverse biological activities: anticancer, antioxidant, anti-inflammatory, neuroprotective and hepatoprotective activities. This review provides information on isolated bioactive phytochemicals and pharmacological potentials of I. britannica.

  8. A retention-time-shift-tolerant background subtraction and noise reduction algorithm (BgS-NoRA) for extraction of drug metabolites in liquid chromatography/mass spectrometry data from biological matrices.

    Science.gov (United States)

    Zhu, Peijuan; Ding, Wei; Tong, Wei; Ghosal, Anima; Alton, Kevin; Chowdhury, Swapan

    2009-06-01

    A retention-time-shift-tolerant background subtraction and noise reduction algorithm (BgS-NoRA) is implemented using the statistical programming language R to remove non-drug-related ion signals from accurate mass liquid chromatography/mass spectrometry (LC/MS) data. The background-subtraction part of the algorithm is similar to a previously published procedure (Zhang H and Yang Y. J. Mass Spectrom. 2008, 43: 1181-1190). The noise reduction algorithm (NoRA) is an add-on feature to help further clean up the residual matrix ion noises after background subtraction. It functions by removing ion signals that are not consistent across many adjacent scans. The effectiveness of BgS-NoRA was examined in biological matrices by spiking blank plasma extract, bile and urine with diclofenac and ibuprofen that have been pre-metabolized by microsomal incubation. Efficient removal of background ions permitted the detection of drug-related ions in in vivo samples (plasma, bile, urine and feces) obtained from rats orally dosed with (14)C-loratadine with minimal interference. Results from these experiments demonstrate that BgS-NoRA is more effective in removing analyte-unrelated ions than background subtraction alone. NoRA is shown to be particularly effective in the early retention region for urine samples and middle retention region for bile samples, where the matrix ion signals still dominate the total ion chromatograms (TICs) after background subtraction. In most cases, the TICs after BgS-NoRA are in excellent qualitative correlation to the radiochromatograms. BgS-NoRA will be a very useful tool in metabolite detection and identification work, especially in first-in-human (FIH) studies and multiple dose toxicology studies where non-radio-labeled drugs are administered. Data from these types of studies are critical to meet the latest FDA guidance on Metabolite in Safety Testing (MIST). Copyright (c) 2009 John Wiley & Sons, Ltd.

  9. Estimation of Ra-226, Ra-228 and K-40 specific activities in fertilizer samples marketed in the Rio de Janeiro City

    Energy Technology Data Exchange (ETDEWEB)

    Garcêz, R.W.D.; Lopes, J.M.; Silva, A. X. da, E-mail: rgarcez@nuclear.ufrj.br [Universidade Federal do Rio de Janeiro (LAASC/UFRJ), Rio de Janeiro, RJ (Brazil). Departamento de Engenharia Nuclear; Lima, M.A.F. [Universidade Federal Fluminense (LARA/UFF), Niterói, RJ (Brazil). Departeamento de Biologia

    2017-07-01

    The use of fertilizers is a common practice in agriculture and several samples have radionuclides in their composition. This content is natural but some samples may have high concentrations of these radionuclides and this represent a potential radiological risk for plants, animals and water. Therefore, the radiometric analyses of these compounds is important, and the aim of this paper is to determine the specific concentration of K-40, Ra-226 and Ra-228 in fertilizer samples available in market of Rio de Janeiro city and discussing the impacts to agricultural soils caused by this practice. Four types of fertilizer samples were analyzed: nitrogen, potash, phosphate and NPK. They were analyzed through gamma spectroscopy technique with a HPGe detector and with the LabSOCS software for the calculation of the efficiency curve. The specific activities of Ra-226 ranged from 1.48 to 597 Bq/kg, Ra-228 ranged from 2.66 to 832 Bq/kg and K-40 ranged from 16 to 13941 Bq/kg. All samples, except two of nitrogen fertilizer, presented the absorbed dose rate in air, at 1m above the ground level, higher than the estimated average global terrestrial radiation for soil (51 nGy/h) and the phosphate fertilizer samples presented the highest average absorbed dose rate: 532.5 nGy/h, which indicates a greater potential of environmental contamination. (author)

  10. Significance of determination of serum cytidine deaminase (CD) levels for diagnosis of active rheumatoid arthritis (RA)

    International Nuclear Information System (INIS)

    Xiao Chuangqing; Jang Xiaogong; He Yunnan

    2005-01-01

    Objective: To determine the clinical value of measurement of serum cytidine deaminase (CD) levels in patients with active rheumatoid arthritis (RA). Methods: Serum levels of CD were detected with spectrophotometry, in 33 patients with active RA and 60 controls. The erythrocyte sedimentation rate (ESR) and CRP content were also determined in both groups. Results: The ser- um CD contents in patients with active RA(14.80 ± 2.11U/ml) were significantly higher than those in controls(4.86±1.86 U/ml,P<0.01). The CRP contents (51.46 ± 20.43mg/L) and ESR readings(85.03 ± 27.6mm/h) in the patients were also significantly higher than those in the controls(3.40 ± 2.21mg/L and 13.04 ± 4.89mm/h respectively, all P<0.01). In the patients, the serum CD contents were linearly positively correlated with the ESR contents and CRP readings (r=0.6324 and 0.8013 respectively, P <0.01). Conclusion: Serum CD is an early biochemical marker for diagnosis of active rheumatoid arthritis and is also of prognostic value. (authors)

  11. RA Reactor; Reaktor RA

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1989-07-01

    This chapter includes the following: General description of the RA reactor, organization of work, responsibilities of leadership and operators team, regulations concerning operation and behaviour in the reactor building, regulations for performing experiments, regulations and instructions for inserting samples into experimental channels. [Serbo-Croat] Ovo (prvo) poglavlje sadrzi sledece: Opis reaktora RA; semu organizacije rada i rukovodjenja; prava i duznosti direktora i rukovodioca pogona reaktora, propise o rezimu rada i kretanja u zgradi reaktora, propise o izvodjenju eksperimenata, propise o unosenju uzoraka u eksperimentalne kanale reaktora.

  12. RA Reactor; Reaktor RA

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1978-02-15

    In addition to basic characteristics of the RA reactor, organizational scheme and financial incentives, this document covers describes the state of the reactor components after 18 years of operation, problems concerned with obtaining the licence for operation with 80% fuel, problems of spent fuel storage in the storage pool of the reactor building and the need for renewal of reactor equipment, first of all instrumentation. [Serbo-Croat] Pored osnovnih karakeristika reaktora RA, organizacije rada i finansijskih pokazatelja, razmatra se stanje opreme reaktora nakon 18 godina rada, pitanja dozvole za rad sa 80% obogacenim gorivom, problem skladistenja isluzenog goriva u bazenu zgrade reaktora i potreba za obnavljanjem komponenti opreme, pre svega elektronske.

  13. Physical activity, sedentary behavior, and vitamin D metabolites.

    Science.gov (United States)

    Hibler, Elizabeth A; Sardo Molmenti, Christine L; Dai, Qi; Kohler, Lindsay N; Warren Anderson, Shaneda; Jurutka, Peter W; Jacobs, Elizabeth T

    2016-02-01

    Physical activity is associated with circulating 25-hydroxyvitamin D (25(OH)D). However, the influence of activity and/or sedentary behavior on the biologically active, seco-steroid hormone 1α,25-dihydroxyvitamin D (1,25(OH)2D) is unknown. We conducted a cross-sectional analysis among ursodeoxycholic acid (UDCA) randomized trial participants (n=876) to evaluate associations between physical activity, sedentary behavior, and circulating vitamin D metabolite concentrations. Continuous vitamin D metabolite measurements and clinical thresholds were evaluated using multiple linear and logistic regression models, mutually adjusted for either 1,25(OH)2D or 25(OH)D and additional confounding factors. A statistically significant linear association between 1,25(OH)2D and moderate-vigorous physical activity per week was strongest among women (β (95% CI): 3.10 (1.51-6.35)) versus men (β (95% CI): 1.35 (0.79-2.29)) in the highest tertile of activity compared to the lowest (p-interaction=0.003). Furthermore, 25(OH)D was 1.54ng/ml (95% CI 1.09-1.98) higher per hour increase in moderate-vigorous activity (p=0.001) and odds of sufficient 25(OH)D status was higher among physically active participants (p=0.001). Sedentary behavior was not significantly associated with either metabolite in linear regression models, nor was a statistically significant interaction by sex identified. The current study identified novel associations between physical activity and serum 1,25(OH)2D levels, adjusted for 25(OH)D concentrations. These results identify the biologically active form of vitamin D as a potential physiologic mechanism related to observed population-level associations between moderate-vigorous physical activity with bone health and chronic disease risk. However, future longitudinal studies are needed to further evaluate the role of physical activity and vitamin D metabolites in chronic disease prevention. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Sulindac metabolites inhibit epidermal growth factor receptor activation and expression

    Directory of Open Access Journals (Sweden)

    Ahnen Dennis

    2005-01-01

    Full Text Available Abstract Background Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs is associated with a decreased mortality from colorectal cancer (CRC. NSAIDs induce apoptotic cell death in colon cancer cells in vitro and inhibit growth of neoplastic colonic mucosa in vivo however, the biochemical mechanisms required for these growth inhibitory effects are not well defined. We previously reported that metabolites of the NSAID sulindac downregulate extracellular-signal regulated kinase 1/2 (ERK1/2 signaling and that this effect is both necessary and sufficient for the apoptotic effects of these drugs. The goal of this project was to specifically test the hypothesis that sulindac metabolites block activation and/or expression of the epidermal growth factor (EGF receptor (EGFR. Methods HT29 human colon cancer cells were treated with EGF, alone, or in the presence of sulindac sulfide or sulindac sulfone. Cells lysates were assayed by immunoblotting for phosphorylated EGFR (pEGFR, pY1068, total EGFR, phosphorylated ERK1/2 (pERK1/2, total ERK1/2, activated caspase-3, and α-tubulin. Results EGF treatment rapidly induced phosphorylation of both EGFR and ERK1/2 in HT29 colon cancer cells. Pretreatment with sulindac metabolites for 24 h blocked EGF-induced phosphorylation of both EGFR and ERK1/2 and decreased total EGFR protein expression. Under basal conditions, downregulation of pEGFR and total EGFR was detected as early as 12 h following sulindac sulfide treatment and persisted through at least 48 h. Sulindac sulfone induced downregulation of pEGFR and total EGFR was detected as early as 1 h and 24 h, respectively, following drug treatment, and persisted through at least 72 h. EGFR downregulation by sulindac metabolites was observed in three different CRC cell lines, occurred prior to the observed downregulation of pERK1/2 and induction of apoptosis by these drugs, and was not dependent of caspase activation. Conclusion These results suggest that

  15. Evaluation of the Ra-226 activity in public-consumption water in the Huarangal Valley using the radiochemical precipitation method as Ba(Ra)SO4

    International Nuclear Information System (INIS)

    Ysla C, M.A.

    1999-01-01

    Five radiochemical methods for Ra-226 determination in public-consumption river waters are developed in this work. Quantification of this radionuclide was conducted through high-resolution gamma spectrometry. These five methods are based on the precipitation of Ra-226 as Ba(Ra)SO 4 . The second of these methods has been considered the best due to its low cost, high radiochemical performance (83,53%) and lowest standard deviation (7,97). Using the second method (standardized method) it was determined that the activity present in a 32 L sample of water is 0,1526 Bq/L. Assuming that each person in Huarangal Valley consumes an average of 2 liters of water a day, we can estimate that this person consumes 111,398 Bq anally, a very low percentage compared to the limit activity reported in other parts of the world. Physicochemical analysis were also conducted in waters of the Chillon river; the results obtained are within the permissible limits established by the World Health Organization, the Institute of Technological, Industrial and Technical Regulation Research (ITINTEC), and the law for Waters of the Ministry of Agriculture. One can conclude, from the physicochemical analysis that have been conducted, that the waters of the Chillon river are fit for public consumption and do not present specific radio-sanitary risks for people living in the Huarangal valley

  16. Pharmacologically active plant metabolites as survival strategy products.

    Science.gov (United States)

    Attardo, C; Sartori, F

    2003-01-01

    The fact that plant organisms produce chemical substances that are able to positively or negatively interfere with the processes which regulate human life has been common knowledge since ancient times. One of the numerous possible examples in the infusion of Conium maculatum, better known as Hemlock, a plant belonging to the family umbelliferae, used by the ancient Egyptians to cure skin diseases. The current official pharmacopoeia includes various chemical substances produced by secondary plant metabolisms. For example, the immunosuppressive drugs used to prevent organ transplant rejection and the majority of antibiotics are metabolites produced by fungal organisms, pilocarpin, digitalis, strophantus, salicylic acid and curare are examples of plant organism metabolites. For this reason, there has been an increase in research into plants, based on information on their medicinal use in the areas where they grow. The study of plants in relation to local culture and traditions is known as "ethnobotany". Careful study of the behaviour of sick animals has also led to the discovery of medicinal plants. The study of this subject is known as "zoopharmacognosy". The aim of this article is to discuss the fact that "ad hoc" production of such chemical substances, defined as "secondary metabolites", is one of the modes in which plant organisms respond to unfavourable environmental stimuli, such as an attack by predatory phytophagous animals or an excessive number of plant individuals, even of the same species, in a terrain. In the latter case, the plant organisms produce toxic substances, called "allelopathic" which limit the growth of other individuals. "Secondary metabolites" are produced by metabolic systems that are shunts of the primary systems which, when required, may be activated from the beginning, or increased to the detriment of others. The study of the manner in which such substances are produced is the subject of a new branch of learning called "ecological

  17. Kynurenine pathway metabolites are associated with hippocampal activity during autobiographical memory recall in patients with depression.

    Science.gov (United States)

    Young, Kymberly D; Drevets, Wayne C; Dantzer, Robert; Teague, T Kent; Bodurka, Jerzy; Savitz, Jonathan

    2016-08-01

    Inflammation-related changes in the concentrations of inflammatory mediators such as c-reactive protein (CRP), interleukin 1β (IL-1), and IL-6 as well as kynurenine metabolites are associated with major depressive disorder (MDD) and affect depressive behavior, cognition, and hippocampal plasticity in animal models. We previously reported that the ratios of kynurenic acid (KynA) to the neurotoxic metabolites, 3-hydroxykynurenine (3HK) and quinolinic acid (QA), were positively correlated with hippocampal volume in depression. The hippocampus is critical for autobiographical memory (AM) recall which is impaired in MDD. Here we tested whether the ratios, KynA/3HK and KynA/QA were associated with AM recall performance as well as hippocampal activity during AM recall. Thirty-five unmedicated depressed participants and 25 healthy controls (HCs) underwent fMRI scanning while recalling emotionally-valenced AMs and provided serum samples for the quantification of kynurenine metabolites, CRP, and cytokines (IL-1 receptor antagonist - IL-1RA; IL-6, tumor necrosis factor alpha - TNF, interferon gamma -IFN-γ, IL-10). KynA/3HK and KynA/QA were lower in the MDD group relative to the HCs. The concentrations of the CRP and the cytokines did not differ significantly between the HCs and the MDD group. Depressed individuals recalled fewer specific AMs and displayed increased left hippocampal activity during the recall of positive and negative memories. KynA/3HK was inversely associated with left hippocampal activity during specific AM recall in the MDD group. Further, KynA/QA was positively correlated with percent negative specific memories recalled in the MDD group and showed a non-significant trend toward a positive correlation with percent positive specific memories recalled in HCs. In contrast, neither CRP nor the cytokines were significantly associated with AM recall or activity of the hippocampus during AM recall. Conceivably, an imbalance in levels of KynA versus QA

  18. Determination of Ra-226, Ra-228 and K-40 specific activities in samples of mineral fertilizer marketed in the Rio de Janeiro City

    International Nuclear Information System (INIS)

    Garcez, R. W. D.; Marques L, J.; Da Silva, A. X.

    2017-10-01

    The use a fertilizers ia a common practice in agriculture and several samples have radionuclides in their composition, this content is natural but some samples may have high concentrations of these radionuclides and this represent a potential radiological risk for plants, animals and water. Therefore the radiometric analyses these compounds is important and the main aim of this paper is to determine the specific concentration of K-40, Ra-226 and Ra-228 in fertilizer samples available in market of Rio de Janeiro city and discussing the impacts to agricultural soils caused by this practice. The analyzed fertilizer samples are of four types: nitrogen, potash, phosphate and NPK, they were analyzed using gamma spectroscopy with a Hp-Ge detector and with the LabSOCS software for the calculation of the efficiency curve. The specific activities of Ra-226 ranged from 1.48 Bq/kg to 597 Bq/kg, Ra-228 ranged from 2.66 Bq/kg to 832 Bq/kg and K-40 ranged from 16 Bq/kg to 13941 Bq/kg. All samples, except two nitrogen fertilizer samples, presented the absorbed dose rate in air at 1 m above the ground level higher than the estimated average global terrestrial radiation of 51 n Gy/h and the phosphate fertilizer samples presented the highest average absorbed dose rate of 532.5 n Gy/h, which indicates a greater potential of environmental contamination. But considering a dilution (1:1000) g of fertilizer in soil was found an average increase of 0.36 μSv/y at the annual outdoor effective dose while the annual average for the soil is of 63 μSv/y, so the risk to human health is minimum. (Author)

  19. Secondary metabolites and biological activity of Pentas species: A minireview

    Directory of Open Access Journals (Sweden)

    Heba-tollah M. Sweelam

    2018-03-01

    Full Text Available The genus Pentas belongs to the Rubiaceae family, which contains approximately 40 species. Several Pentas species were reported to be used as a folk treatment by African indigenous people in treating some diseases such as malaria, tapeworms, dysentery, gonorrhea, syphilis and snake poisoning. This article covers the period from 1962 to 2017 and presents an overview of the biological activity of different Pentas species and describes their phytochemical traits. As a conclusion, the main secondary metabolites from Pentas species are quinones, highly oxygenated chromene-based structures, and iridoids. Pentas species are widely used in folk medicine but they have to be more investigated for their medicinal properties.

  20. Measuring the radium quartet (228Ra, 226Ra, 224Ra, 223Ra) in seawater samples using gamma spectrometry

    International Nuclear Information System (INIS)

    Beek, P. van; Souhaut, M.; Reyss, J.-L.

    2010-01-01

    Radium isotopes are widely used in marine studies (eg. to trace water masses, to quantify mixing processes or to study submarine groundwater discharge). While 228 Ra and 226 Ra are usually measured using gamma spectrometry, short-lived Ra isotopes ( 224 Ra and 223 Ra) are usually measured using a Radium Delayed Coincidence Counter (RaDeCC). Here we show that the four radium isotopes can be analyzed using gamma spectrometry. We report 226 Ra, 228 Ra, 224 Ra, 223 Ra activities measured using low-background gamma spectrometry in standard samples, in water samples collected in the vicinity of our laboratory (La Palme and Vaccares lagoons, France) but also in seawater samples collected in the plume of the Amazon river, off French Guyana (AMANDES project). The 223 Ra and 224 Ra activities determined in these samples using gamma spectrometry were compared to the activities determined using RaDeCC. Activities determined using the two techniques are in good agreement. Uncertainties associated with the 224 Ra activities are similar for the two techniques. RaDeCC is more sensitive for the detection of low 223 Ra activities. Gamma spectrometry thus constitutes an alternate method for the determination of short-lived Ra isotopes.

  1. Prompt gamma neutron activation analysis facility at the RA-6 research reactor

    International Nuclear Information System (INIS)

    Sanchez, F. A.; Calzetta, O

    2004-01-01

    A prompt gamma neutron activation activation analysis facility was developed at the 500 kw thermal power RA-6 research reactor of the Bariloche Atomic Center, Argentina.This facility consist of a radial beam port with external positioning of the sample.The gamma radiation is reduced by a bismuth filter placed inside the extraction tube and the beam diameter is limited by a set of two collimators up to 5 cm.The neutron flux at the sample position is 7 10 6 n/cm 2 s with a Cadmium ratio of 20/1.The gamma detector is a 50 % efficiency type p HPGe rounded by a NaI(Tl) for Compton suppressioning.The gamma spectra is measured through 0 to 8.5 MeV.The background have counting rate of 350 cps without sample. In this work is shown the efficiency curve, the calculed sensibilities and the lower detection limits for B, Cd, Sm, Gd, H, Cl, Hg, Eu, Ti, Ag, Au, Mo. The RA-6's PGNAA facility is fully working, although the analytic capacity is under improvement [es

  2. Shared care or nurse consultations as an alternative to rheumatologist follow-up for rheumatoid arthritis (RA) outpatients with stable low disease-activity RA

    DEFF Research Database (Denmark)

    Sørensen, Jan; Primdahl, J; Horn, Hc

    2014-01-01

    per quality-adjusted life year (QALY) threshold, shared care and nurse care were cost-effective with more than 90% probability. Nurse care was cost-effective in comparison with shared care with 75% probability. Conclusions: Shared care and nurse care seem to cost less but provide broadly similar......Objectives: To compare the cost-effectiveness of three types of follow-up for outpatients with stable low-activity rheumatoid arthritis (RA). Method: In total, 287 patients were randomized to either planned rheumatologist consultations, shared care without planned consultations, or planned nurse...... consultations. Effectiveness measures included disease activity (Disease Activity Score based on 28 joint counts and C-reactive protein, DAS28-CRP), functional status (Health Assessment Questionnaire, HAQ), and health-related quality of life (EuroQol EQ-5D). Cost measures included activities in outpatient...

  3. Molecular neutron activation analysis of selenium metabolites in urine

    International Nuclear Information System (INIS)

    Blotcky, A.J.; Hansen, G.T.; Ebrahim, A.; Rack, E.P.

    1988-01-01

    Because of the biological importance of selenium in living biological systems, various analytical procedures have been developed for analysis of microquantities of elemental selenium, in urine, serum, and tissue. For urine selenium, these include atomic absorption spectrometry, solution absorption spectrometry, solution fluorescence spectrometry, volumetry, and neutron activation analysis. Of equal or greater importance is the determination of selenium metabolites present in urine for the purpose of describing the biological pathways for the metabolism of selenium in living organisms. While it is known from previous studies that trimethylselenonium ion (TMSe) is a major metabolite in urine, probably the result of reduction and methylation reaction, there are no definitive results in the literature indicating the nature or quantity of other selenium metabolic products in urine. Early techniques to measure TMSe levels in urine involved the use of the radiotracer 75 Se. Because of the long biological half-life of selenium and issues of radiation exposure, its use in humans has been limited. In this paper, the authors report the experimental procedure for the determination of total selenoamino acid concentration in urine and present total selenium values, and, where applicable, TMSe, SeO 2- 3 , and total selenoamino acid concentrations in the urine of normal and diseased subjects

  4. Removal of 226Ra, Fe3+ and Mn2+ from ground water using modified activated carbon

    International Nuclear Information System (INIS)

    Daifullah, A.A.M.

    2003-01-01

    A locally available biomass material, rice husk, was carbonized and activated in a steam/nitrogen flow by the use of a bench-scale fluidized bed reactor. The virgin carbon prepared from rice husk was further treated chemically using an alkali (e.g.10% NaOH and 10% KOH) in order to change the surface basicity of the carbon or oxidized with 30%H 2 O 2 and 10% HNO 3 in order to introduce different oxygen surface complexes. The modified carbons were characterized by FTIR and elemental analysis and investigated for removing unacceptably high concentrations of 326 Ra from ground water. The results showed that the best removal was obtained by the virgin carbon. The effect of process variables such as: contact time, Ph, carbon mass, sorbent surface modification and cation interference (e.g.iron and manganese) on the removal efficiency by the virgin carbon was studied. The data was fitted to Freundlich adsorption equation. Recommended procedures were adapted for complete removal of 226 Ra, Fe 3+ and Mn 2+ from ground water. Treated water quality remained good and no significant external radiation dose was caused to the residents

  5. Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristics, and treatments in the QUEST-RA study.

    Science.gov (United States)

    Sokka, Tuulikki; Toloza, Sergio; Cutolo, Maurizio; Kautiainen, Hannu; Makinen, Heidi; Gogus, Feride; Skakic, Vlado; Badsha, Humeira; Peets, Tõnu; Baranauskaite, Asta; Géher, Pál; Ujfalussy, Ilona; Skopouli, Fotini N; Mavrommati, Maria; Alten, Rieke; Pohl, Christof; Sibilia, Jean; Stancati, Andrea; Salaffi, Fausto; Romanowski, Wojciech; Zarowny-Wierzbinska, Danuta; Henrohn, Dan; Bresnihan, Barry; Minnock, Patricia; Knudsen, Lene Surland; Jacobs, Johannes Wg; Calvo-Alen, Jaime; Lazovskis, Juris; Pinheiro, Geraldo da Rocha Castelar; Karateev, Dmitry; Andersone, Daina; Rexhepi, Sylejman; Yazici, Yusuf; Pincus, Theodore

    2009-01-01

    Gender as a predictor of outcomes of rheumatoid arthritis (RA) has evoked considerable interest over the decades. Historically, there is no consensus whether RA is worse in females or males. Recent reports suggest that females are less likely than males to achieve remission. Therefore, we aimed to study possible associations of gender and disease activity, disease characteristics, and treatments of RA in a large multinational cross-sectional cohort of patients with RA called Quantitative Standard Monitoring of Patients with RA (QUEST-RA). The cohort includes clinical and questionnaire data from patients who were seen in usual care, including 6,004 patients at 70 sites in 25 countries as of April 2008. Gender differences were analyzed for American College of Rheumatology Core Data Set measures of disease activity, DAS28 (disease activity score using 28 joint counts), fatigue, the presence of rheumatoid factor, nodules and erosions, and the current use of prednisone, methotrexate, and biologic agents. Women had poorer scores than men in all Core Data Set measures. The mean values for females and males were swollen joint count-28 (SJC28) of 4.5 versus 3.8, tender joint count-28 of 6.9 versus 5.4, erythrocyte sedimentation rate of 30 versus 26, Health Assessment Questionnaire of 1.1 versus 0.8, visual analog scales for physician global estimate of 3.0 versus 2.5, pain of 4.3 versus 3.6, patient global status of 4.2 versus 3.7, DAS28 of 4.3 versus 3.8, and fatigue of 4.6 versus 3.7 (P < 0.001). However, effect sizes were small-medium and smallest (0.13) for SJC28. Among patients who had no or minimal disease activity (0 to 1) on SJC28, women had statistically significantly higher mean values compared with men in all other disease activity measures (P < 0.001) and met DAS28 remission less often than men. Rheumatoid factor was equally prevalent among genders. Men had nodules more often than women. Women had erosions more often than men, but the statistical significance

  6. Activity concentration and population dose from 226Ra due to consumption of dietary components

    International Nuclear Information System (INIS)

    Wagh, S.S.; Patra, A.K.; Ravi, P.M.; Sarkar, P.K.

    2012-01-01

    226 Ra (T 1/2 = 1620 years, α-energy 4.78 MeV, 4.59 MeV, γ-energy 186 keV), a product of natural uranium decay series, is abundantly observed in natural environment. Radium, along with its homologue calcium, an essential element in the plant system, is absorbed from the soil by plants and gets redistributed. within different parts of the plants. Because of the long half-life of 226 Ra, it gets accumulated in the human body for along time. The hazard due to ingestion of 226 Ra dissolved in water is reported to be about 40 times higher than that of 90 Sr. This paper deals with the concentration of 226 Ra in different dietary components and ingestion dose from 226 Ra due to consumption of dietary components. Internal radiation exposure to non-human biota due to 226 Ra is also discussed

  7. Composition and Antioxidant Activity of Geopropolis Collected by Melipona subnitida (Jandaíra) Bees.

    Science.gov (United States)

    Alves de Souza, Silvana; Camara, Celso Amorim; Monica Sarmento da Silva, Eva; Silva, Tania Maria Sarmento

    2013-01-01

    An investigation of the geopropolis collected by Melipona subnitida (jandaíra) stingless bee led to the isolation and characterization of two phenylpropanoids, 6-O-p-coumaroyl-D-galactopyranose (1) and 6-O-cinnamoyl-1-O-p-coumaroyl- β -D-glucopyranose (2), and seven flavonoids, 7-O-methyl-naringenin (3), 7-O-methyl aromadendrin (4), 7,4'-di-O-methyl aromadendrin (5), 4'-O-methyl kaempferol (6), 3-O-methyl quercetin (7), 5-O-methyl aromadendrin (8), and 5-O-methyl kaempferol (9). The structure of the new phenylpropanoid (1) was established from IR, LC-ESI-MS, and NMR spectral data, including 2D NMR experiments. The extract and fractions demonstrated significant antioxidant activity in DPPH, ABTS, and β -carotene/linoleic acid tests.

  8. Composition and Antioxidant Activity of Geopropolis Collected by Melipona subnitida (Jandaíra Bees

    Directory of Open Access Journals (Sweden)

    Silvana Alves de Souza

    2013-01-01

    Full Text Available An investigation of the geopropolis collected by Melipona subnitida (jandaíra stingless bee led to the isolation and characterization of two phenylpropanoids, 6-O-p-coumaroyl-D-galactopyranose (1 and 6-O-cinnamoyl-1-O-p-coumaroyl-β-D-glucopyranose (2, and seven flavonoids, 7-O-methyl-naringenin (3, 7-O-methyl aromadendrin (4, 7,4′-di-O-methyl aromadendrin (5, 4′-O-methyl kaempferol (6, 3-O-methyl quercetin (7, 5-O-methyl aromadendrin (8, and 5-O-methyl kaempferol (9. The structure of the new phenylpropanoid (1 was established from IR, LC-ESI-MS, and NMR spectral data, including 2D NMR experiments. The extract and fractions demonstrated significant antioxidant activity in DPPH, ABTS, and β-carotene/linoleic acid tests.

  9. Serum progranulin irrelated with Breg cell levels, but elevated in RA patients, reflecting high disease activity.

    Science.gov (United States)

    Chen, Jiaxi; Li, Shuang; Shi, Jianfeng; Zhang, Lili; Li, Jun; Chen, Shiyong; Wu, Chunlong; Shen, Bo

    2016-03-01

    Soluble progranulin (PGRN) is known to directly regulate regulatory T cells; however, whether PGRN levels are elevated in patients with rheumatoid arthritis and affect the regulatory subsets of B cells remain unknown. In this study, a total of 80 RA patients and 60 healthy controls were studied. Serum progranulin levels were determined using enzyme-linked immune-sorbent assay. A receiver operating characteristic (ROC) curve was used to evaluate the feasibility of serum PGRN as a biomarker for distinguishing patients with RA. CD19(+)CD5(+)GrB(+) B cells were analyzed by flow cytometry in peripheral blood mononuclear cells (PBMCs). Serum progranulin levels in RA patients (median, 59.4 ng/mL) and in RA patients DAS28 > 5.1 (median, 71.98 ng/mL) were much higher than those in normal controls (median, 46.3 ng/mL; P progranulin levels was 0.705 for RA versus normal controls and the area under the ROC curve for progranulin levels in RA patients DAS28 > 5.1 was 0.977 versus normal controls (P progranulin and DAS28, CRP, ESR were all positively correlated in RA patients (P 0.05). Our findings indicated that induction of PGRN expression may play a role in RA immune reaction and PGRN levels could be a useful biomarker in RA inflammatory response, but irrelated with Breg cell levels.

  10. Antifouling Activity of Secondary Metabolites Isolated from Chinese Marine Organisms

    KAUST Repository

    Li, Yong Xin

    2013-04-25

    Biofouling results in tremendous economic losses to maritime industries around the world. A recent global ban on the use of organotin compounds as antifouling agents has further raised demand for safe and effective antifouling compounds. In this study, 49 secondary metabolites, including diterpenoids, steroids, and polyketides, were isolated from soft corals, gorgonians, brown algae, and fungi collected along the coast of China, and their antifouling activity was tested against cyprids of the barnacle Balanus (Amphibalanus) amphitrite. Twenty of the compounds were found to inhibit larval settlement significantly at a concentration of 25 μg ml-1. Two briarane diterpenoids, juncin O (2) and juncenolide H (3), were the most promising non-toxic antilarval settlement candidates, with EC50 values less than 0.13 μg ml-1 and a safety ratio (LC50/EC50) higher than 400. A preliminary structure-activity relationships study indicated that both furanon and furan moieties are important for antifouling activity. Intriguingly, the presence of hydroxyls enhanced their antisettlement activity. © 2013 Springer Science+Business Media New York.

  11. Antifouling Activity of Secondary Metabolites Isolated from Chinese Marine Organisms

    KAUST Repository

    Li, Yong Xin; Wu, Hui Xian; Xu, Ying; Shao, Chang Lun; Wang, Chang Yun; Qian, Pei Yuan

    2013-01-01

    Biofouling results in tremendous economic losses to maritime industries around the world. A recent global ban on the use of organotin compounds as antifouling agents has further raised demand for safe and effective antifouling compounds. In this study, 49 secondary metabolites, including diterpenoids, steroids, and polyketides, were isolated from soft corals, gorgonians, brown algae, and fungi collected along the coast of China, and their antifouling activity was tested against cyprids of the barnacle Balanus (Amphibalanus) amphitrite. Twenty of the compounds were found to inhibit larval settlement significantly at a concentration of 25 μg ml-1. Two briarane diterpenoids, juncin O (2) and juncenolide H (3), were the most promising non-toxic antilarval settlement candidates, with EC50 values less than 0.13 μg ml-1 and a safety ratio (LC50/EC50) higher than 400. A preliminary structure-activity relationships study indicated that both furanon and furan moieties are important for antifouling activity. Intriguingly, the presence of hydroxyls enhanced their antisettlement activity. © 2013 Springer Science+Business Media New York.

  12. Evaluation of Ra, Th, K and radium equivalent activity in sand samples from Camburi Beach, Vitoria, Espirito Santos, Brazil

    International Nuclear Information System (INIS)

    Barros, Livia F.; Pecequilo, Brigitte R.S.

    2013-01-01

    Camburi beach, in the city of Vitoria, Espirito Santo State. Brazil, is a naturally high background region in Brazil. The beach sands contain monazite, ilmenite and other accessory minerals rich in 226 Ra, 23 '2Th and 40 K. As these radionuclides are the main natural contributors to external exposure from gamma rays, the knowledge of the sands radioactivity content plays an important role in radiation protection. In this work, 226 Ra, 232 Th and 40 K activities concentrations, together with the radium equivalent activity, Ra eq. were determined in some selected sand samples from a single location at Camburi beach, known for the high level of radioactivity. The sand samples collected monthly from January to December 2011, were dried and sealed in standard 100 mL HPDE polyethylene flasks and measured by high resolution gamma-spectrometry after a 4 weeks ingrowth period, in order to allow the secular equilibrium in the 238 U and 23 '2Th series. Preliminary results, without considering samples self-attenuation, show activities concentrations in the range from 12 ± 1 Bq kg -1 to 1022 ± 30 Bq kg -1 for 226 Ra, 35 ± 1 Bq kg -1 to 5731 ± 134 Bq kg -1 for 232 Th and 18 ± 4 Bqkg -1 to 430 ± 21 Bq kg -1 for 40 K. The Ra eq , presented values ranging from 63 Bq kg -1 to 9250 Bq kg -1 . (author)

  13. Determination of specific activities of U-238, Ra-226, Ra-228 e Th-228 in samples of mineral fertilizers with phosphorus; Determinacao das atividades especificas de U-238, Ra-226, Ra-228 e Th-228 em amostras de fertilizantes minerais com fosforo

    Energy Technology Data Exchange (ETDEWEB)

    Garcez, R.W.D.; Lopes, J.M.; Silva, A.X. da, E-mail: rgarcez@nuclear.ufrj.br [Coordenacao dos Programas de Pos-Graduacao em Engenharoa (COPPE/UFRJ), Rio de Janeiro, RJ (Brazil). Programa de Engenharia Nuclear; Domingues, A.M.; Lima, M.A.F. [Universidade Federal Fluminense (UFF),Niteroi, RJ (Brazil)

    2016-07-01

    Samples were analyzed by gamma spectrometry mineral fertilizers with the HPGe detector and aid LabSOCS software for calculating the detection efficiency curve. Specific activities found for Pa-234m, Ra-226, Ra-228 and Th-228 in samples of phosphate fertilizers were 505 Bq.kg{sup -1}, 458 Bq.kg{sup -1}, 450 Bq.kg{sup -1} and 394 Bq.kg{sup -1}, respectively. And for the NPK fertilizer samples were found average values of 390 Bq.kg{sup -1}, 252 Bq.kg{sup -1}, 280 Bq.kg{sup -1} and 268 Bq.kg{sup -1}, respectively. (author)

  14. Evaluation of the activity concentration of {sup 226}Ra, {sup 228}Ra and {sup 210}Pb in sediments from Antarctica in the Admiralty bay region; Avaliacao da concentracao de atividade de Ra-226, Ra-228 e Pb-210 em sedimentos provenientes da Antartica na regiao da baia do Almirantado

    Energy Technology Data Exchange (ETDEWEB)

    Mora, Tamires de Araujo

    2015-07-01

    The natural radionuclides from radioactive series of {sup 238}U, {sup 235}U and {sup 232}Th have been applied as tracers in environmental studies for understanding the dynamics that occur in both marine and terrestrial environment, as for example, in research of oceanic processes and management of the coastal region. In the marine environment, these radionuclides can be used to estimate biogeochemical fluxes of marine particles and nutrients that occur in the water column as well as in the sediment. Several research works applied the distribution and the respective disequilibrium degree of natural radionuclides in the environment, including geochronological models for obtaining historical information on samples of certain sediment profile. In this study we performed a radiochemical characterization of the distribution of {sup 226}Ra, {sup 228}Ra and {sup 210}Pb from a sedimentary column called 1B (248 cm long) collected in the Admiralty Bay, Antarctic Peninsula region. The methodology used included the acid leaching of sediment samples followed by the radiochemical sequential separation of {sup 226}Ra and {sup 228}Ra by co-precipitation with Ba(Ra)SO{sub 4} and {sup 210}Pb by co-precipitation with PbCrO{sub 4}. All measurements were carried out by counting of gross alpha and gross beta measures in a low background gas flow proportional detector. The activity concentrations of {sup 226}Ra and {sup 210}Pb were used to estimate the unsupported {sup 210}Pb activities present in sediment profile 1 B. Based on unsupported {sup 210}Pb data and the application of the CIC model (Constant Initial Concentration), it was possible to determine the sedimentation rate of 0.59 ± 0.05 cm /year. (author)

  15. Activity concentrations of 226Ra, 232Th and 40K in brands of fertilisers used in Nigeria

    International Nuclear Information System (INIS)

    Jibiri, N. N.; Fasae, K. P.

    2012-01-01

    The activity concentration of naturally occurring radionuclides 40 K, 226 Ra and 232 Th have been measured in different brands of fertiliser samples sold to farmers in retail markets in six commercial cities in southwestern Nigeria. Gamma ray spectroscopy was employed in the measurements of these radionuclides. The results of measurements showed that the average activity concentration of 40 K in the nitrogen, phosphorus and potassium fertilisers across the cities varied from 3972.0 ±416.9 to 5089.3 ±111.3 Bq kg -1 , 9.9 ±7.3 to 450.6 ±14.3 Bq kg -1 for 226 Ra, while for 232 Th it varied from less than lower limit of detection to 15.1 ±2.8 Bq kg -1 . The activity concentrations of 40 K, 226 Ra and 232 Th in single super phosphate (SSP) fertilisers and phosphate rocks were also determined. However, high activity concentrations of 226 Ra were obtained in the SSP fertiliser and phosphate rocks and in particular, two brands of fertilisers from ITL/TAK and F and C companies. The values of the activity concentration of the radionuclides in the brands of fertilisers used in Nigeria are within the range of values reported in several other countries except 40 K. (authors)

  16. A Review of the Secondary Metabolites and Biological Activities of ...

    African Journals Online (AJOL)

    School of Chemical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia ... ulcers. A wide range of secondary metabolites such as alkaloids, diterpenes, flavones, phenolics, and triterpenes .... potency than the synthetic antioxidant.

  17. Effect of competition on the production and activity of secondary metabolites in Aspergillus species

    DEFF Research Database (Denmark)

    Losada, L.; Ajayi, O.; Frisvad, Jens Christian

    2009-01-01

    and in the presence of other fungal species. However, it is not known whether secreted secondary metabolites provide a competitive advantage over other fungal species, or whether competition has any effect on the production of those metabolites. Here, we have performed co-cultivation competition assays among......Secondary metabolites are of intense interest to humans due to their pharmaceutical and/or toxic properties. Also, these metabolites are clinically relevant because of their importance in fungal pathogenesis. Aspergillus species secrete secondary metabolites when grown individually...... different species of Aspergillus to determine relative species fitness in culture, and to analyze the presence of possible antifungal activity of secondary metabolites in extracts. The results show that, for the most part, at 30C only one species is able to survive direct competition with a second species...

  18. Determination of 226Ra and 228Ra in gypsum

    International Nuclear Information System (INIS)

    Godoy, J.M.

    1989-01-01

    The content of 226 Ra and 228 Ra in different samples of phosphogypsum and three samples of gypsite were determined by gamma spectroscopy. For 226 Ra the 295, 352 and 609 KeV lines and for 228 Ra the 911 and 969 KeV lines were used. The specific activities values ranged from 0.36 to 22.8 pCi/g for 226 Ra and 0.90 to 10.3 pCi/g for 228 Ra. The contribution of a sypsum roof-covering to the 222 Rn concentration in a room was estimated, based on the highest value reported. (author) [pt

  19. Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST-RA database.

    Science.gov (United States)

    Sokka, T; Kautiainen, H; Pincus, T; Toloza, S; da Rocha Castelar Pinheiro, G; Lazovskis, J; Hetland, M L; Peets, T; Immonen, K; Maillefert, J F; Drosos, A A; Alten, R; Pohl, C; Rojkovich, B; Bresnihan, B; Minnock, P; Cazzato, M; Bombardieri, S; Rexhepi, S; Rexhepi, M; Andersone, D; Stropuviene, S; Huisman, M; Sierakowski, S; Karateev, D; Skakic, V; Naranjo, A; Baecklund, E; Henrohn, D; Gogus, F; Badsha, H; Mofti, A; Taylor, P; McClinton, C; Yazici, Y

    2009-11-01

    To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country. The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 "high GDP" countries with GDP per capita greater than US$24,000 and 11 "low GDP" countries with GDP per capita less than US$11,000. Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r = -0.78, 95% CI -0.56 to -0.90, r(2) = 61%). Disease activity levels differed substantially between "high GDP" and "low GDP" countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents. The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in "low GDP" than in "high GDP" countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries.

  20. Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST–RA database

    Science.gov (United States)

    Sokka, T; Kautiainen, H; Pincus, T; Toloza, S; da Rocha Castelar Pinheiro, G; Lazovskis, J; Hetland, M L; Peets, T; Immonen, K; Maillefert, J F; Drosos, A A; Alten, R; Pohl, C; Rojkovich, B; Bresnihan, B; Minnock, P; Cazzato, M; Bombardieri, S; Rexhepi, S; Rexhepi, M; Andersone, D; Stropuviene, S; Huisman, M; Sierakowski, S; Karateev, D; Skakic, V; Naranjo, A; Baecklund, E; Henrohn, D; Gogus, F; Badsha, H; Mofti, A; Taylor, P; McClinton, C; Yazici, Y

    2009-01-01

    Objective: To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country. Methods: The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST–RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 “high GDP” countries with GDP per capita greater than US$24 000 and 11 “low GDP” countries with GDP per capita less than US$11 000. Results: Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r  =  −0.78, 95% CI −0.56 to −0.90, r2  =  61%). Disease activity levels differed substantially between “high GDP” and “low GDP” countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents. Conclusions: The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in “low GDP” than in “high GDP” countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries. PMID:19643759

  1. 226Ra activity in the mullet species Liza aurata and South Adriatic sea marine environment of Montenegro

    International Nuclear Information System (INIS)

    Antovic, N. M.; Antovic, I.; Svrkota, N.

    2010-01-01

    226 Ra activity in the South Adriatic Sea-water, surface sediment, mud with detritus, sea-grass (Posidonia oceanica) samples and the mullet (Mugilidae) species Liza aurata, as well as soil and sand from the Montenegrin Coast-was measured using the six-crystal gamma-coincidence spectrometer PRIPYAT-2M. The results are used for calculation of the absorbed (and annual effective) dose rates in air due to the 226 Ra gamma radiation. The absorbed dose rates ranged from 5.94 to 97.16 nGy h -1 (soil) and from 0.65 to 7.65 nGy h -1 (sand). In seawater 226 Ra activity is found to be from 0.08 to 0.15 Bq l -1 , while in whole L. aurata individuals from 0.58 to 1.97 Bq kg -1 . Annual intake of 226 Ra by human consumers of this fish species has been estimated to provide an effective dose of 0.006 mSv y -1 . (authors)

  2. Studies on sup(226) Ra and sup(210) Pb activities and the concentration factors of sup(226) Ra in the surface organic layers of the estuarine sediments of Mindola and Purna rivers in India

    Digital Repository Service at National Institute of Oceanography (India)

    Joshi, L.U.; Zingde, M.D.; Desai, B.N.

    ., to the sediment floor The activities of sup(226) Ra are found to vary from 0.1 to 0.5 pCi/g, while sup(210) Pb activities lie in the range of 3 to 8 pCi/g These activities find their way into the organisms present in sea water and then into fish which is finally...

  3. Evaluation of Ra, Th, K and radium equivalent activity in sand samples from Camburi Beach, Vitoria, Espirito Santos, Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Barros, Livia F.; Pecequilo, Brigitte R.S., E-mail: lfbarros@ipen.br, E-mail: brigitte@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    Camburi beach, in the city of Vitoria, Espirito Santo State. Brazil, is a naturally high background region in Brazil. The beach sands contain monazite, ilmenite and other accessory minerals rich in {sup 226}Ra, {sup 23}'2Th and {sup 40}K. As these radionuclides are the main natural contributors to external exposure from gamma rays, the knowledge of the sands radioactivity content plays an important role in radiation protection. In this work, {sup 226}Ra, {sup 232}Th and {sup 40}K activities concentrations, together with the radium equivalent activity, Ra{sub eq.} were determined in some selected sand samples from a single location at Camburi beach, known for the high level of radioactivity. The sand samples collected monthly from January to December 2011, were dried and sealed in standard 100 mL HPDE polyethylene flasks and measured by high resolution gamma-spectrometry after a 4 weeks ingrowth period, in order to allow the secular equilibrium in the {sup 238}U and {sup 23}'2Th series. Preliminary results, without considering samples self-attenuation, show activities concentrations in the range from 12 {+-} 1 Bq kg{sup -1} to 1022 {+-} 30 Bq kg{sup -1} for {sup 226}Ra, 35 {+-} 1 Bq kg{sup -1} to 5731 {+-} 134 Bq kg{sup -1} for {sup 232}Th and 18 {+-} 4 Bqkg{sup -1} to 430 {+-} 21 Bq kg{sup -1} for {sup 40}K. The Ra{sub eq}, presented values ranging from 63 Bq kg{sup -1} to 9250 Bq kg{sup -1}. (author)

  4. A Review of the Secondary Metabolites and Biological Activities of ...

    African Journals Online (AJOL)

    Tinospora crispa Beumee, a herbaceous climber, has been widely used in traditional medicine for treating various ailments such as contusion, septicaemia, fever, fracture, scabies and other tropical ulcers. A wide range of secondary metabolites such as alkaloids, diterpenes, flavones, phenolics, and triterpenes have been ...

  5. Urinary Estrogen Metabolites, Active and Sedentary Behaviors, and Breast Cancer Risk

    Science.gov (United States)

    A cross-sectional study of approximately 600 postmenopausal controls in the Breast Cancer Case-Control Study in Poland to assess urinary estrogen metabolites in relation to accelerometer-based measures of active and sedentary behaviors

  6. The Synthesis of Active Metabolites and Analogues of Vitamin D3

    Science.gov (United States)

    Yakhimovich, R. I.

    1980-04-01

    The literature date on the synthesis of the active metabolites and analogues of vitamin D3 (cholecalciferol), which play an important role in regulating the homeostatis of calcium in the organism, are reviewed. The bibliography includes 150 references.

  7. Study of the specific activity concentrations of 40K, {sup 226}Ra, {sup 228}Ra and {sup 232}Th in vegetables and their respective covering tissues (peels)

    Energy Technology Data Exchange (ETDEWEB)

    Lopes, J.M.; Garcêz, R.W.D., E-mail: marqueslopez@yahoo.com.br [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil). Programa de Engenharia Nuclear; Silva, A.X. [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil). Escola Politécnica

    2017-07-01

    This work presents an analysis of specific concentrations of {sup 40}K, {sup 226}Ra, {sup 228}Ra and {sup 232}Th in some vegetables that are part of the diet of the population of the state of Rio de Janeiro. Furthermore, was analyzed the concentrations of radionuclides in the same coating tissue that compose the vegetables. It can notice an increase of the specific concentration of {sup 40}K in the peels of vegetables that have little or no contact with the ground. Among the samples examined, only the pumpkin showed measurable amount of {sup 137}Cs both saves and in the skin. (author)

  8. Study of the specific activity concentrations of 40K, 226Ra, 228Ra and 232Th in vegetables and their respective covering tissues (peels)

    International Nuclear Information System (INIS)

    Lopes, J.M.; Garcêz, R.W.D.; Silva, A.X.

    2017-01-01

    This work presents an analysis of specific concentrations of 40 K, 226 Ra, 228 Ra and 232 Th in some vegetables that are part of the diet of the population of the state of Rio de Janeiro. Furthermore, was analyzed the concentrations of radionuclides in the same coating tissue that compose the vegetables. It can notice an increase of the specific concentration of 40 K in the peels of vegetables that have little or no contact with the ground. Among the samples examined, only the pumpkin showed measurable amount of 137 Cs both saves and in the skin. (author)

  9. Chemopreventive Activities of Sulforaphane and Its Metabolites in Human Hepatoma HepG2 Cells

    Directory of Open Access Journals (Sweden)

    Peng Liu

    2018-05-01

    Full Text Available Sulforaphane (SFN exhibits chemopreventive effects through various mechanisms. However, few studies have focused on the bioactivities of its metabolites. Here, three metabolites derived from SFN were studied, known as sulforaphane glutathione, sulforaphane cysteine and sulforaphane-N-acetylcysteine. Their effects on cell viability, DNA damage, tumorigenicity, cell migration and adhesion were measured in human hepatoma HepG2 cells, and their anti-angiogenetic effects were determined in a 3D co-culture model of human umbilical vein endothelial cells (HUVECs and pericytes. Results indicated that these metabolites at high doses decreased cancer cell viability, induced DNA damage and inhibited motility, and impaired endothelial cell migration and tube formation. Additionally, pre-treatment with low doses of SFN metabolites protected against H2O2 challenge. The activation of the nuclear factor E2-related factor 2 (Nrf2-antioxidant response element (ARE pathway and the induction of intracellular glutathione (GSH played an important role in the cytoprotective effects of SFN metabolites. In conclusion, SFN metabolites exhibited similar cytotoxic and cytoprotective effects to SFN, which proves the necessity to study the mechanisms of action of not only SFN but also of its metabolites. Based on the different tissue distribution profiles of these metabolites, the most relevant chemical forms can be selected for targeted chemoprevention.

  10. Niacin and its metabolites as master regulators of macrophage activation.

    Science.gov (United States)

    Montserrat-de la Paz, Sergio; Naranjo, M Carmen; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J Garcia; Bermudez, Beatriz

    2017-01-01

    Niacin is a broad-spectrum lipid-regulating drug used for clinical therapy of chronic high-grade inflammatory diseases. However, the mechanisms by which either niacin or the byproducts of its catabolism ameliorate these inflammatory diseases are not clear yet. Human circulating monocytes and mature macrophages were used to analyze the effects of niacin and its metabolites (NAM, NUA and 2-Pyr) on oxidative stress, plasticity and inflammatory response by using biochemical, flow cytometry, quantitative real-time PCR and Western blot technologies. Niacin, NAM and 2-Pyr significantly decreased ROS, NO and NOS2 expression in LPS-treated human mature macrophages. Niacin and NAM skewed macrophage polarization toward antiinflammatory M2 macrophage whereas a trend toward proinflammatory M1 macrophage was noted following treatment with NUA. Niacin and NAM also reduced the inflammatory competence of LPS-treated human mature macrophages and promoted bias toward antiinflammatory CD14 + CD16 ++ nonclassical human primary monocytes. This study reveals for the first time that niacin and its metabolites possess antioxidant, reprogramming and antiinflammatory properties on human primary monocytes and monocyte-derived macrophages. Our findings imply a new understanding of the mechanisms by which niacin and its metabolites favor a continuous and gradual plasticity process in the human monocyte/macrophage system. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Strategies to enhance biologically active-secondary metabolites in cell cultures of Artemisia - current trends.

    Science.gov (United States)

    Ali, Mohammad; Abbasi, Bilal Haider; Ahmad, Nisar; Khan, Haji; Ali, Gul Shad

    2017-11-01

    The genus Artemisia has been utilized worldwide due to its immense potential for protection against various diseases, especially malaria. Artemisia absinthium, previously renowned for its utilization in the popular beverage absinthe, is gaining resurgence due to its extensive pharmacological activities. Like A. annua, this species exhibits strong biological activities like antimalarial, anticancer and antioxidant. Although artemisinin was found to be the major metabolite for its antimalarial effects, several flavonoids and terpenoids are considered to possess biological activities when used alone and also to synergistically boost the bioavailability of artemisinin. However, due to the limited quantities of these metabolites in wild plants, in vitro cultures were established and strategies have been adopted to enhance medicinally important secondary metabolites in these cultures. This review elaborates on the traditional medicinal uses of Artemisia species and explains current trends to establish cell cultures of A. annua and A. absinthium for enhanced production of medicinally important secondary metabolites.

  12. Measuring the radium quartet ({sup 228}Ra, {sup 226}Ra, {sup 224}Ra, {sup 223}Ra) in seawater samples using gamma spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Beek, P. van, E-mail: vanbeek@legos.obs-mip.f [LEGOS, Laboratoire d' Etudes en Geophysique et Oceanographie Spatiales (CNRS/CNES/IRD/UPS), Observatoire Midi Pyrenees, 14 Avenue Edouard Belin, 31400 Toulouse (France); Souhaut, M. [LEGOS, Laboratoire d' Etudes en Geophysique et Oceanographie Spatiales (CNRS/CNES/IRD/UPS), Observatoire Midi Pyrenees, 14 Avenue Edouard Belin, 31400 Toulouse (France); Reyss, J.-L. [LSCE, Laboratoire des Sciences du Climat et de l' Environnement (CNRS/CEA/UVSQ), Avenue de la Terrasse, 91198 Gif-sur-Yvette (France)

    2010-07-15

    Radium isotopes are widely used in marine studies (eg. to trace water masses, to quantify mixing processes or to study submarine groundwater discharge). While {sup 228}Ra and {sup 226}Ra are usually measured using gamma spectrometry, short-lived Ra isotopes ({sup 224}Ra and {sup 223}Ra) are usually measured using a Radium Delayed Coincidence Counter (RaDeCC). Here we show that the four radium isotopes can be analyzed using gamma spectrometry. We report {sup 226}Ra, {sup 228}Ra, {sup 224}Ra, {sup 223}Ra activities measured using low-background gamma spectrometry in standard samples, in water samples collected in the vicinity of our laboratory (La Palme and Vaccares lagoons, France) but also in seawater samples collected in the plume of the Amazon river, off French Guyana (AMANDES project). The {sup 223}Ra and {sup 224}Ra activities determined in these samples using gamma spectrometry were compared to the activities determined using RaDeCC. Activities determined using the two techniques are in good agreement. Uncertainties associated with the {sup 224}Ra activities are similar for the two techniques. RaDeCC is more sensitive for the detection of low {sup 223}Ra activities. Gamma spectrometry thus constitutes an alternate method for the determination of short-lived Ra isotopes.

  13. Tests of biological activity of metabolites from Penicillium expansum (Link Thom various isolates

    Directory of Open Access Journals (Sweden)

    Halina Borecka

    2013-12-01

    Full Text Available Aqrobacterium tumefaciens and cucumber, mustard and linseeds were compared as test organisms for evaluation of the biological activity of patulin. It was found that the reaction of cucumber seeds and linseed to the patulin concentrations was more pronounced than that of mustard and Aqrobacterium tumefaciens. The activity of metabolites produced by Penicillium expansum was investigated with the use of cucumber seeds. As measure of activity served the percentage of radicule growth inhibition was compared with the growth in control seeds. The biological activity of the metabolites was specific for the isolates, those from apples being more active. Thirty two isolates from pears and 34 from apples were examined.

  14. 226Ra, 228Ra and 228Ra/226Ra in surface marine sediment of Malaysia

    International Nuclear Information System (INIS)

    Mei-Wo Yii; Zal Uyun Wan-Mahmood

    2013-01-01

    Surface sediment samples were collected at the West (east coast and west coast of Peninsular Malaysia) and East (Sabah and Sarawak) Malaysia in several expeditions within August 2003 until June 2008 for determining the level of natural radium isotopes. Activity concentrations of 226 Ra and 228 Ra in surface marine sediment at 176 sampling stations were measured. The activity concentrations of both radionuclides in Malaysia (East and West Malaysia) display varied with the range from 9 to 158 Bq/kg dry wt. and 13 to 104 Bq/kg dry wt., respectively. Meanwhile, the ratio distributions of 228 Ra/ 226 Ra were ranged from 0.62 to 3.75. This indicated that the ratios were slightly high at west coast of Peninsular Malaysia compared to other regions (east coast of Peninsular Malaysia, Sabah and Sarawak). The variation of activity concentrations of 226 Ra and 228 Ra and its ratios were also supported by the statistical analyses of one-way ANOVA and t test at 95 % confidence level, whereby there were proved that the measured values were different between the regions. These different were strictly related to their half-life, potential input sources (included their parents, 238 U and 232 Th), parent's characteristic, the geological setting/formation of the study area, environment origin and behavior. (author)

  15. RA Reactor

    International Nuclear Information System (INIS)

    1989-01-01

    This chapter includes the following: General description of the RA reactor, organization of work, responsibilities of leadership and operators team, regulations concerning operation and behaviour in the reactor building, regulations for performing experiments, regulations and instructions for inserting samples into experimental channels [sr

  16. Use of prokaryotic transcriptional activators as metabolite biosensors in eukaryotic cells

    DEFF Research Database (Denmark)

    2018-01-01

    The present invention relates to the use of transcriptional activators from prokaryotic organisms for use in eukaryotic cells, such as yeast as sensors of intracellular and extracellular accumulation of a ligand or metabolite specifically activating this transcriptional activator in a eukaryot...

  17. Diversity of Secondary Metabolites from Marine Bacillus Species: Chemistry and Biological Activity

    Science.gov (United States)

    Mondol, Muhammad Abdul Mojid; Shin, Hee Jae; Islam, Mohammad Tofazzal

    2013-01-01

    Marine Bacillus species produce versatile secondary metabolites including lipopeptides, polypeptides, macrolactones, fatty acids, polyketides, and isocoumarins. These structurally diverse compounds exhibit a wide range of biological activities, such as antimicrobial, anticancer, and antialgal activities. Some marine Bacillus strains can detoxify heavy metals through reduction processes and have the ability to produce carotenoids. The present article reviews the chemistry and biological activities of secondary metabolites from marine isolates. Side by side, the potential for application of these novel natural products from marine Bacillus strains as drugs, pesticides, carotenoids, and tools for the bioremediation of heavy metal toxicity are also discussed. PMID:23941823

  18. PhosphoLipid transfer protein (PLTP) exerts a direct pro-inflammatory effect on rheumatoid arthritis (RA) fibroblasts-like-synoviocytes (FLS) independently of its lipid transfer activity

    Science.gov (United States)

    Deckert, Valérie; Daien, Claire I.; Che, Hélène; Elhmioui, Jamila; Lemaire, Stéphanie; Pais de Barros, Jean-Paul; Desrumaux, Catherine; Combe, Bernard; Hahne, Michael; Lagrost, Laurent; Morel, Jacques

    2018-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory rheumatic disease with modification of lipids profile and an increased risk of cardiovascular events related to inflammation. Plasma phospholipid transfer protein (PLTP) exerts a lipid transfer activity through its active form. PLTP can also bind to receptors such as ATP-binding cassette transporter A1 (ABCA1). In addition to its role in lipoprotein metabolism and atherosclerosis, the latest advances came in support of a complex role of PLTP in the regulation of the inflammatory response, both with pro-inflammatory or anti-inflammatory properties. The aim of the present study was to decipher the role of PLTP in joint inflammation and to assess its relevance in the context of RA. PLTP expression was examined by western-blot and by immunochemistry. ABCA1 expression was analyzed by flow cytometry. Lipid transfer activity of PLTP and pro-inflammatory cytokines were measured in sera and synovial fluid (SF) from RA patients and controls (healthy subjects or osteoarthritis patients [OA]). FLS were treated with both lipid-transfer active form and inactive form of recombinant human PLTP. IL-8, IL-6, VEGF and MMP3 produced by FLS were assessed by ELISA, and proliferation by measuring 3H-Thymidine incorporation. RA synovial tissues showed higher PLTP staining than OA and PLTP protein levels were also significantly higher in RA-FLS. In addition, RA, unlike OA patients, displayed elevated levels of PLTP activity in SF, which correlated with pro-inflammatory cytokines. Both lipid-transfer active and inactive forms of PLTP significantly increased the production of cytokines and proliferation of FLS. ABCA1 was expressed on RAFLS and PLTP activated STAT3 pathway. To conclude, PLTP is highly expressed in the joints of RA patients and may directly trigger inflammation and FLS proliferation, independently of its lipid transfer activity. These results suggest a pro-inflammatory role for PLTP in RA. PMID:29565987

  19. RA Reactor

    International Nuclear Information System (INIS)

    1978-02-01

    In addition to basic characteristics of the RA reactor, organizational scheme and financial incentives, this document covers describes the state of the reactor components after 18 years of operation, problems concerned with obtaining the licence for operation with 80% fuel, problems of spent fuel storage in the storage pool of the reactor building and the need for renewal of reactor equipment, first of all instrumentation [sr

  20. Biological activity of anthocyanins and their phenolic degradation products and metabolites in human vascular endothelial cells

    OpenAIRE

    Edwards, Michael

    2013-01-01

    Human, animal, and in vitro data indicate significant vasoprotective activity of anthocyanins. However, few studies have investigated the activity of anthocyanin degradation products and metabolites which are likely to mediate bioactivity in vivo. The present thesis therefore examined the vascular bioactivity in vitro of anthocyanins, their phenolic degradants, and the potential for interactions between dietary bioactive compounds. Seven treatment compounds (cyanidin-, peonidin-, petunidin- &...

  1. Widespread occurrence of neuro-active pharmaceuticals and metabolites in 24 Minnesota rivers and wastewaters

    Science.gov (United States)

    Writer, Jeffrey; Ferrer, Imma; Barber, Larry B.; Thurman, E. Michael

    2013-01-01

    Concentrations of 17 neuro-active pharmaceuticals and their major metabolites (bupropion, hydroxy-bupropion, erythro-hydrobupropion, threo-hydrobupropion, carbamazepine, 10,11,-dihydro-10,11,-dihydroxycarbamazepine, 10-hydroxy-carbamazepine, citalopram, N-desmethyl-citalopram, fluoxetine, norfluoxetine, gabapentin, lamotrigine, 2-N-glucuronide-lamotrigine, oxcarbazepine, venlafaxine and O-desmethyl-venlafaxine), were measured in treated wastewater and receiving surface waters from 24 locations across Minnesota, USA. The analysis of upstream and downstream sampling sites indicated that the wastewater treatment plants were the major source of the neuro-active pharmaceuticals and associated metabolites in surface waters of Minnesota. Concentrations of parent compound and the associated metabolite varied substantially between treatment plants (concentrations ± standard deviation of the parent compound relative to its major metabolite) as illustrated by the following examples; bupropion and hydrobupropion 700 ± 1000 ng L−1, 2100 ± 1700 ng L−1, carbamazepine and 10-hydroxy-carbamazepine 480 ± 380 ng L−1, 360 ± 400 ng L−1, venlafaxine and O-desmethyl-venlafaxine 1400 ± 1300 ng L−1, 1800 ± 2300 ng L−1. Metabolites of the neuro-active compounds were commonly found at higher or comparable concentrations to the parent compounds in wastewater effluent and the receiving surface water. Neuro-active pharmaceuticals and associated metabolites were detected only sporadically in samples upstream from the effluent outfall. Metabolite to parent ratios were used to evaluate transformation, and we determined that ratios in wastewater were much lower than those reported in urine, indicating that the metabolites are relatively more labile than the parent compounds in the treatment plants and in receiving waters. The widespread occurrence of neuro-active pharmaceuticals and metabolites in Minnesota effluents and surface waters indicate that

  2. Current activities on improving storage conditions of the research reactor RA spent fuel - Part II

    International Nuclear Information System (INIS)

    Matausek, M.V.; Kopecni, M.; Vukadin, Z.; Plecas, I.; Pavlovic, R.; Sotic, O.; Marinkovic, N.

    1998-01-01

    To minimize further corrosion and preserve integrity of aluminum barrels and the stainless steel channel-type containers that were found to contain leaking spent fuel, actions to improve conditions in the existing spent fuel storage pool at the RA research reactor were initiated. Technology was elaborated and equipment was produced and applied for removal of sludge and other debris from the bottom of the pool, filtration of the pool water, sludge conditioning in cement matrix and disposal at the low and medium waste repository at VINCA site. More sophisticated operations are to be performed together with foreign experts. Safety measures and precautions were determined. Subcriticality was proved under normal and/or possible abnormal conditions. (author)

  3. Estrogenic activities of diuron metabolites in female Nile tilapia (Oreochromis niloticus).

    Science.gov (United States)

    Pereira, Thiago Scremin Boscolo; Boscolo, Camila Nomura Pereira; Felício, Andreia Arantes; Batlouni, Sergio Ricardo; Schlenk, Daniel; de Almeida, Eduardo Alves

    2016-03-01

    Some endocrine disrupting chemicals (EDCs) can alter the estrogenic activities of the organism by directly interacting with estrogen receptors (ER) or indirectly through the hypothalamus-pituitary-gonadal axis. Recent studies in male Nile tilapia (Oreochromis niloticus) indicated that diuron may have anti-androgenic activity augmented by biotransformation. In this study, the effects of diuron and three of its metabolites were evaluated in female tilapia. Sexually mature female fish were exposed for 25 days to diuron, as well as to its metabolites 3,4-dichloroaniline (DCA), 3,4-dichlorophenylurea (DCPU) and 3,4-dichlorophenyl-N-methylurea (DCPMU), at concentrations of 100 ng/L. Diuron metabolites caused increases in E2 plasma levels, gonadosomatic indices and in the percentage of final vitellogenic oocytes. Moreover, diuron and its metabolites caused a decrease in germinative cells. Significant differences in plasma concentrations of the estrogen precursor and gonadal regulator17α-hydroxyprogesterone (17α-OHP) were not observed. These results show that diuron metabolites had estrogenic effects potentially mediated through enhanced estradiol biosynthesis and accelerated the ovarian development of O. niloticus females. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Determination of specific activity of 226Ra, 232Th and 40K for assessment of environmental hazards

    International Nuclear Information System (INIS)

    Al-Haydari, A.; Al Sharabi, E. S. A.; Al Buhairi, M. H.

    2012-01-01

    Studies have been carried out using gamma-spectrometric techniques to determine the natural radioactivity in some rocks that are used as building materials in Yemen. The concentrations of the natural radionuclides namely 226 Ra, 232 Th and 40 K in the rock samples collected from different rock markets in Yemen have been determined using an NaI(Tl) detector. The concentrations of 226 Ra, 232 Th and 40 K in the studied rock samples range from 22.2 to 88.8 Bq kg -1 , 8.12 to 113.68 Bq kg -1 and 31.3 to 2222.3 Bq kg -1 , respectively. The concentrations of these radionuclides are compared with the typical world values. To evaluate the radiological hazard of the natural radioactivity, the radium equivalent activity, the air absorbed dose rate, the annual effective dose rate, the representative level index and the values of both external and internal hazard indices were evaluated and compared with the internationally approved values. The radium equivalent activity values of all rock samples are lower than the limit of 370 Bq kg -1 except for one sample which is about 413.386. The values of external hazard index (H ex ) and internal hazard index (H in ), absorbed doses in indoor air and the corresponding effective dose equivalents in a typical dwelling are presented. The need for further studies is also discussed. (authors)

  5. The measurement of activities of 226Ra, 232Th, 40K in phosphogypsum by gamma ray spectrometry

    International Nuclear Information System (INIS)

    Parmaksiz, A.

    2004-06-01

    Phosphatic fertilizers are produced from the industrial processing of rock phosphate ores which are known to contain naturally occuring radionuclides such as 238 U and its daughter products. A high volume by-product known as phosphogypsum (PG) from the production of phosphoric acid and phosphate fertilizer causes serious storage and environmental problems in phosphoric acid industries. During the phosphoric acid production process, 226 Ra (t 1/2 =1600 y) ends up in PG which has chemical analogous to calcium periodical table. Since the stockpiles of PG near the phosphatic fertilizer plants are huge amounts, the radioactivity contained in PG has to measured in view of environmental radioactivity problem. In this work, the natural radioactivity in eighty PG samples, issued from a stock of about 60.000 tones was measured by a high resolution gamma ray spectrometer with a HPGe detector. The averaged activity of 226 Ra in PG has been found to be 546 Bq.kg -1 . However, the activities of 232 Th and 40 K measured in PG samples are negligibly small. The extra gamma radiation dose rate arising from 1 - 1.5 kg of PG is estimated to be about 241 nGy/h from 1 m ground level applied in 1 m 2 surface area of field

  6. Activity concentration and radiological impact assessment of 226Ra, 228Ra and 40K in drinking waters from (OML) 30, 58 and 61 oil fields and host communities in Niger Delta region of Nigeria

    International Nuclear Information System (INIS)

    Agbalagba, E.O.; Avwiri, G.O.; Ononugbo, C.P.

    2013-01-01

    This paper presents the concentrations of naturally occurring radionuclides ( 226 Ra, 228 Ra and 40 K) measured in hand dug wells, boreholes and river waters collected from three oil mineral leases (OML) 30, 58 and 61 oil and gas fields onshore of the Niger delta, using gamma spectroscopy. Fifty-four water samples from the three sources of drinking water supply were collected within the oil fields and host communities and three water samples from a control site. The results showed average activity concentrations of 226 Ra, 228 Ra and 40 K as 8.9 ± 1.0, 8.1 ± 0.9 and 39.8 ± 3.3 respectively for hand dug wells, 4.4 ± 0.8, 4.6 ± 0.5 and 28.5 ± 3.0 for borehole water and 8.2 ± 1.0, 6.7 ± 0.7 and 32.1 ± 3.5 for river water respectively. These 226 Ra, 228 Ra and 40 K average are well above the WHO permissible levels of 1.0, 0.1 and 10 BqL −1 respectively and also above the control values. Although the hazard indices calculated are still within their tolerable levels, the estimated committed effective dose due to intake of the sampled water for all the four age groups considered are far above the ICPR 0.1 mSvyr −1 maximum permissible limit. The result indicates some level of water pollution in the studied area. - Highlights: ► The concentration of natural radioactive series nuclides varies widely within oil fields and from one oil field to another in the OML30. ► The radionuclide activity concentrations in most water samples are higher than world average values. ► Calculated hazard indices and committed effective dose to assess the potential radiological health risk in samples are well above their permissible limit. ► The sources of water in these oil fields have been polluted and may cause some health hazard to the public users.

  7. Determination of urine metabolites containing radioactivatable elements by molecular neutron activation analysis

    International Nuclear Information System (INIS)

    Blotcky, A.J.; Rack, E.P.

    1986-01-01

    As urine is a final stage for the metabolic pathways of essential trace elements or chemical toxins, it is becoming increasingly important to not only report levels of trace elements but to determine the molecular or ionic identity of these trace elements. For a biological system such as urine, a molecular neutron activation analysis (MONAA) approach must involve a deproteinization step, where necessary, to ensure that metabolites such as amino acids, bases, r nucleosides are not protein bound prior to chemical separation. This can involve the simple application of ammonia or acid hydrolysis. All separations for the metabolites containing the radioactivatable element must be performed prior to neutron irradiation and subsequent radioassay for the metabolite. Separation procedures can include high-pressure liquid chromotography (HPLC), ion-exchange chromatography, size exclusion chromatography, solvent extraction, and/or gas chromatography. After separation, the separated metabolite is neutron irradiated and and radioassayed for the radioactivity in the metabolite. A review of previous work involving the determination of hormonal iodine, iodoamino acids, chlorinated pesticides, trimethyl-selenonium, and selenoamino acids in urine is discussed

  8. 226Ra, 228Ra, 223Ra, and 224Ra in coastal waters with application to coastal dynamics and groundwater input

    International Nuclear Information System (INIS)

    Moore, W.S.

    1997-01-01

    Four radium isotopes offer promise in unraveling the complex dynamics of coastal ocean circulation and groundwater input. Each isotope is produced by decay of a thorium parent bound to sediment. The activities of these thorium isotopes and the sediment-water distribution coefficient for radium provide an estimate of the source function of each Ra isotope to the water. In salt marshes that receive little surface water input, Ra activities which exceed coastal ocean values must originate within the marsh. In North Inlet, South Carolina, the activities of 226 Ra exported from the marsh far exceed the activities generated within the marsh. To supply the exported activities, substantial groundwater input is required. In the coastal region itself, 226 Ra activities exceed the amount that can be supplied from rivers. Here also, substantial groundwater input is required. Within the coastal ocean, 223 Ra and 224 Ra may be used to determine mixing rates with offshore waters. Shore-perpendicular profiles of 223 Ra and 224 Ra show consistent trends which may be modeled as eddy diffusion coefficients of 350-540 m 2 s -1 . These coefficients allow an assessment of cross-shelf transport and provide further insight on the importance of groundwater to coastal regions. (author)

  9. CHARACTERIZATION ADN BIOLOGICAL ACTIVITY OF SECONDARY METABOLITES FROM ARMILLARIA TABESCENS

    Science.gov (United States)

    Ethyl acetate extracts from liquid cultures of Armillaria tabescens showed good antimicrobial activity against Candida albicans, Cryptococcus neoformans, Escherichia coli and Mycobacterium intracellulare. Chemical analyses of extract constituents led to the isolation and identification of two new co...

  10. Determination of secondary metabolites and antioxidant activity of ...

    African Journals Online (AJOL)

    justify the ethno-therapeutic usage of these plants by traditional healers. Keywords: Boraginaceae ... direct relationship between antioxidant activities and phenolic contents .... The diode array UV detector and the mobile phases, including (A) ...

  11. Engineering prokaryotic transcriptional activators as metabolite biosensors in yeast

    DEFF Research Database (Denmark)

    Skjødt, Mette Louise; Snoek, Tim; Kildegaard, Kanchana Rueksomtawin

    2016-01-01

    ,cis-muconic acid at different levels, and found that reporter gene output correlated with production. The transplantation of prokaryotic transcriptional activators into the eukaryotic chassis illustrates the potential of a hitherto untapped biosensor resource useful for biotechnological applications....... real-time monitoring of production has attracted attention. Here we applied systematic engineering of multiple parameters to search for a general biosensor design in the budding yeast Saccharomyces cerevisiae based on small-molecule binding transcriptional activators from the prokaryote superfamily...

  12. Estuarine geochemistry of 224Ra, 226Ra, and 222Rn

    International Nuclear Information System (INIS)

    Elsinger, R.J.

    1982-01-01

    Desorption from river borne sediments is the most likely source of the excess 226 Ra. Laboratory mixing experiments on Pee Dee River sediments show an increase in 226 Ra desorption with increasing salinities with maximum desorption occurring at or above 20 0 /oo salinity. Desorption and diffusion are the sources for 226 Ra in the estuarine systems. In Winyah Bay the 228 Ra/ 226 Ra activity ratio does not change significantly with salinity, averaging around 1.4, indicating desorption as the major source of 228 Ra. In the Yangtze River the 228 Ra/ 226 Ra activity ratio is constant (approx.1.90) until increasing linearly above 16 0 /oo. A diffusive flux from regeneration by 232 Th decay in shelf sediments is the source of the increase. In Delaware Bay 228 Ra increases faster than 226 Ra in the less than or equal to22 0 /oo water, indicating a source in addition to desorption. The increase can be balanced by a 0.33 dpm/cm 2 -year flux over the upper part of the Bay where fine grained sediments predominate. 224 Ra behavior is controlled by its 3.64 day half-life. In Winyah Bay a flux of around 0.4 dpm/cm 2 -day is necessary to support the standing crop of non-desorbed 224 Ra in the water column. In Delaware Bay the nearly constant 224 Ra in concentration over the 2.5 0 /oo to 12 0 /oo salinity range are maintained by regeneration from 228 Th in the turbidity maximum zones and diffusion from bottom sediments. Water leaving on ebb tide from a salt marsh on Delaware Bay had increases in all three radium isotopes ( 224 Ra > 228 Ra > 226 Ra) compared to water coming in on the flood tide. Excess 222 Rn concentrations in a fresh water section of the Pee Dee River show a decreasing downstream gradient. Using these gradients to determine evasion rates, stagnant film thicknesses range from 21μ to 62μ

  13. The formation of estrogen-like tamoxifen metabolites and their influence on enzyme activity and gene expression of ADME genes.

    Science.gov (United States)

    Johänning, Janina; Kröner, Patrick; Thomas, Maria; Zanger, Ulrich M; Nörenberg, Astrid; Eichelbaum, Michel; Schwab, Matthias; Brauch, Hiltrud; Schroth, Werner; Mürdter, Thomas E

    2018-03-01

    Tamoxifen, a standard therapy for breast cancer, is metabolized to compounds with anti-estrogenic as well as estrogen-like action at the estrogen receptor. Little is known about the formation of estrogen-like metabolites and their biological impact. Thus, we characterized the estrogen-like metabolites tamoxifen bisphenol and metabolite E for their metabolic pathway and their influence on cytochrome P450 activity and ADME gene expression. The formation of tamoxifen bisphenol and metabolite E was studied in human liver microsomes and Supersomes™. Cellular metabolism and impact on CYP enzymes was analyzed in upcyte® hepatocytes. The influence of 5 µM of tamoxifen, anti-estrogenic and estrogen-like metabolites on CYP activity was measured by HPLC MS/MS and on ADME gene expression using RT-PCR analyses. Metabolite E was formed from tamoxifen by CYP2C19, 3A and 1A2 and from desmethyltamoxifen by CYP2D6, 1A2 and 3A. Tamoxifen bisphenol was mainly formed from (E)- and (Z)-metabolite E by CYP2B6 and CYP2C19, respectively. Regarding phase II metabolism, UGT2B7, 1A8 and 1A3 showed highest activity in glucuronidation of tamoxifen bisphenol and metabolite E. Anti-estrogenic metabolites (Z)-4-hydroxytamoxifen, (Z)-endoxifen and (Z)-norendoxifen inhibited the activity of CYP2C enzymes while tamoxifen bisphenol consistently induced CYPs similar to rifampicin and phenobarbital. On the transcript level, highest induction up to 5.6-fold was observed for CYP3A4 by tamoxifen, (Z)-4-hydroxytamoxifen, tamoxifen bisphenol and (E)-metabolite E. Estrogen-like tamoxifen metabolites are formed in CYP-dependent reactions and are further metabolized by glucuronidation. The induction of CYP activity by tamoxifen bisphenol and the inhibition of CYP2C enzymes by anti-estrogenic metabolites may lead to drug-drug-interactions.

  14. Application of metabolite profiling and antioxidant activity in ...

    African Journals Online (AJOL)

    This paper investigates the effect of processing and extraction method on chemical profiles and antioxidant activity of Malaysian stingless bee propolis. High Performance Thin Layer Chromatography (HPTLC) analysis in combination with chemometric shows that some of the compounds were degraded or not detected in ...

  15. Biological activities of secondary metabolites of the order Zoanthids

    Directory of Open Access Journals (Sweden)

    Zahra Aminikhoei

    2015-11-01

    Full Text Available The phylum Cnidaria is a large, diverse and ecologically important group of marine invertebrates, which produce powerful toxins and venoms. The number of marine natural product from cnidarians isolated from class Anthozoa. Among the Anthozoa, the order of zoanthids are sessile, clonal and mostly brightly colored invertebrate which produce high biodiversity of cytolitic, neurotoxic and cardiotoxic compounds. Zoanthids containing palytoxins are reportedly among the most toxic marine organisms known. In addition, a high concentration of zoanthamine alkaloids extracted from this group.The zoanthamine alkaloids were isolated over 20 years ago, exhibit a broad range of biological activities.The best studied and most well-known biological activity of zoanthamine derivative significantly suppressed bone resorption and enhanced bone formation.

  16. RA research nuclear reactor - Annual report 1985; Istrazivacki nuklearni reaktor RA - Izvestaj za 1985. godinu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1985-12-01

    Research reactor RA Annual report for year 1985 is divided into two main parts to cover: (1) operation and maintenance and (2) activities related to radiation protection. [Serbo-Croat] Godisnji izvestaj po projektu 'Istrazivacki nuklearni reaktor RA' za 1985 godinu sastoji se od dva dela: prvi deo obuhvata pogon i odzavanje reaktora RA, a drugi poslove zastite od zracenja na reaktoru RA.

  17. RA Research reactor, Annual report 1986; Istrazivacki nuklearni reaktor RA - Izvestaj za 1986. godinu

    Energy Technology Data Exchange (ETDEWEB)

    Sotic, O [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

    1986-12-01

    Research reactor RA Annual report for year 1985 is divided into two main parts to cover: (1) operation and maintenance and (2) activities related to radiation protection. [Serbo-Croat] Godisnji izvestaj po projektu 'Istrazivacki nuklearni reaktor RA' za 1986 godinu sastoji se od dva dela: prvi deo obuhvata pogon i odzavanje reaktora RA, a drugi poslove zastite od zracenja na reaktoru RA.

  18. Eurotium (Aspergillus) repens metabolites and their biological activity.

    Science.gov (United States)

    Podojil, M; Sedmera, P; Vokoun, J; Betina, V; Baráthová, H; Duracková, Z; Horáková, K; Nemec, P

    1978-01-01

    Eurotium repens mycelium cultivated under static conditions was used to isolate and identify metabolities--echinulin, physcion, erythroglaucin, flavoglaucin and asperentin; the filtrate of the culture yielded asperentin 8-methylether. The broadest biological activity spectrum was displayed by asperentin which had antibacterial and antifungal effects and, at a concentration of 86 microgram/ml, caused 50% mor7 tality in Artemia saline larvae. The highest cytotoxicity towards HeLa cells was found in physcion which caused 50% growth inhibition at a concentration of 0.1 microgram/ml.

  19. Anti-androgenic activities of diuron and its metabolites in male Nile tilapia (Oreochromis niloticus).

    Science.gov (United States)

    Pereira, Thiago Scremin Boscolo; Boscolo, Camila Nomura Pereira; Silva, Danilo Grünig Humberto da; Batlouni, Sergio Ricardo; Schlenk, Daniel; Almeida, Eduardo Alves de

    2015-07-01

    Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is a widely used herbicide which has been frequently detected in surface waters throughout the world. In vivo bioassay guided fractionation studies indicated that diuron may have estrogenic activity augmented by biotransformation. This study evaluated the effects of diuron and three of its metabolites on plasma hormone concentrations and spermatogenesis of the freshwater fish Nile tilapia (Oreochromis niloticus). Sexually mature male fish were exposed for 25 days to diuron, as well to its metabolites 3,4-dichloroaniline (DCA), 3,4-dichlorophenylurea (DCPU) and 3,4-dichlorophenyl-N-methylurea (DCPMU), at concentrations of 200ng/L. Testosterone levels were decreased by diuron, but had limited effects on gonadal histology. Diuron metabolites, however, caused significant decreases in testosterone and in 11-ketotestosterone, gonadosomatic index, diameter of seminiferous tubules and in the mean percentages of germ cells (spermatids and spermatozoa). We conclude that these metabolites have antiandrogenic activity to male Nile tilapia, potentially causing reproductive impairment in male fish. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Antifouling Activity of Lipidic Metabolites Derived from Padina tetrastromatica.

    Science.gov (United States)

    Suresh, Murugan; Iyapparaj, Palanisamy; Anantharaman, Perumal

    2016-07-01

    An attempt has been made to identify the potential seaweed for antifouling property due to the growing need for environmentally safe antifouling systems. The antibacterial, antimicroalgal, and antimussel foot adherence potentials of methanol, dichloromethane, and hexane extracts of the chosen seaweeds such as Padina tetrastromatica, Caulerpa taxifolia, and Amphiroa fragilissima have been compared against copper sulfate. Among the extracts, the maximum antibacterial activities were exhibited by the methanol extract of P. tetrastromatica. The minimum inhibitory concentration (MIC) of the methanolic extract of P. tetrastromatica was found to be 10 and 1 μg/ml against test biofilm bacteria and diatoms, respectively. The antimussel foot adherence assay indicated that the extract had inhibited the foot adherence of the green mussels Perna viridis with the effective concentration (EC50) of 25.51 ± 0.03 μg/ml, and lethal concentration for 50 % mortality (LC50) was recorded at 280.22 ± 0.12 μg/ml. Based on the prolific results, the crude methanolic extract of P. tetrastromatica was subjected to purification using silica gel column and thin-layer chromatography (TLC). Then, the active compounds of the bioassay-guided fraction (F13) were identified using gas chromatography coupled with mass spectroscopy (GC-MS), and it was observed that fatty acids were the major components, which may be responsible for the antifouling properties.

  1. The 226Ra isotope activities in ground water samples drawn of two wells from the Meridional Pluton, Morungaba Granitoids, eastern Sao Paulo State; Atividades do 226Ra em aguas subterraneas extraidas de dois pocos localizados no pluton meridional, granitoides de Morungaba, SP

    Energy Technology Data Exchange (ETDEWEB)

    Lucas, Fabio de Oliveira; Silva Junior, Mario Goncalves da; Bertolla, Luciana; Ribeiro, Fernando Brenha [Sao Paulo Univ., SP (Brazil). Inst. de Astronomia, Geofisica e Ciencias Atmosfericas. Dept. de Geofisica]. E-mail: brenha@iag.usp.br

    2005-07-01

    The 226Ra activities, both in solution and associated with suspended solids, were measured in ground water samples drawn from two wells drilled in a fractured granitic aquifer from the Meridional Pluton, Morungaba Granitoids, eastern Sao Paulo State. The 226Ra isotope activities were measured in a sequence of samples collected about one month apart between March, 2003 and April 2004. The 226Ra activities were measured by radon gas emanometry. The mean dissolved 226Ra activity concentration activities observed in the two wells were (44.9 {+-} 7.1) mBq/L and (51.6 {+-} 8.8) mBq/L. The 226Ra activity of the suspend solids in a liter of these waters varied between (0,6 {+-} 0,1) mBq and (13 {+-} 1) mBq, respectively. (author)

  2. The antibacterial activity of syringopicroside, its metabolites and natural analogues from syringae folium

    KAUST Repository

    Zhou, Zhengyuan; Han, Na; Liu, Zhihui; Song, Zehai; Wu, Peng; Shao, Jingxuan; Zhang, Jiaming; Yin, Jun

    2016-01-01

    In the present study, the in vitro antibacterial activity of an effective fraction (ESF) from Syringae Folium (SF) on Methicillin-resistant Staphylococcus aureus (MRSA) was evaluated and then its in vivo activity was evaluated by using the MRSA-infected mouse peritonitis model. The ESF showed a significant in vitro and in vivo activity on decreasing the Minimum Inhibitory Concentrations (MICs) and increasing the survival rate of mouse from 42.8% to 100%. Six iridoid glucosides (IGs) of ESF were characterized by UPLC-TOF-MS method and also isolated by column chromatography. Most of them showed in vitro anti MRSA activity. Syringopicroside (Sy), the major compound of IGs, was found to increase the survival rate from 42.8% to 92.8% of the MRSA-infected mouse, which revealed Sy is also the main active components of ESF. In order to know why the effect of oral administration of SF is better than its injections in clinic and the metabolites of Sy, seven metabolites of Sy were isolated from rat urine and identified on the basis of NMR and MS spectra. Most of metabolites possessed stronger in vitro anti-MRSA activity than that of Sy, which furtherly proved the clinical result.

  3. The antibacterial activity of syringopicroside, its metabolites and natural analogues from syringae folium

    KAUST Repository

    Zhou, Zhengyuan

    2016-02-18

    In the present study, the in vitro antibacterial activity of an effective fraction (ESF) from Syringae Folium (SF) on Methicillin-resistant Staphylococcus aureus (MRSA) was evaluated and then its in vivo activity was evaluated by using the MRSA-infected mouse peritonitis model. The ESF showed a significant in vitro and in vivo activity on decreasing the Minimum Inhibitory Concentrations (MICs) and increasing the survival rate of mouse from 42.8% to 100%. Six iridoid glucosides (IGs) of ESF were characterized by UPLC-TOF-MS method and also isolated by column chromatography. Most of them showed in vitro anti MRSA activity. Syringopicroside (Sy), the major compound of IGs, was found to increase the survival rate from 42.8% to 92.8% of the MRSA-infected mouse, which revealed Sy is also the main active components of ESF. In order to know why the effect of oral administration of SF is better than its injections in clinic and the metabolites of Sy, seven metabolites of Sy were isolated from rat urine and identified on the basis of NMR and MS spectra. Most of metabolites possessed stronger in vitro anti-MRSA activity than that of Sy, which furtherly proved the clinical result.

  4. Evaluation of the in vitro activity of levornidazole, its metabolites and comparators against clinical anaerobic bacteria.

    Science.gov (United States)

    Hu, Jiali; Zhang, Jing; Wu, Shi; Zhu, Demei; Huang, Haihui; Chen, Yuancheng; Yang, Yang; Zhang, Yingyuan

    2014-12-01

    This study evaluated the in vitro anti-anaerobic activity and spectrum of levornidazole, its metabolites and comparators against 375 clinical isolates of anaerobic bacteria, including Gram-negative bacilli (181 strains), Gram-negative cocci (11 strains), Gram-positive bacilli (139 strains) and Gram-positive cocci (44 strains), covering 34 species. Minimum inhibitory concentrations (MICs) of levornidazole, its five metabolites and three comparators against these anaerobic isolates were determined by the agar dilution method. Minimum bactericidal concentrations (MBCs) of levornidazole and metronidazole were measured against 22 strains of Bacteroides fragilis. Levornidazole showed good activity against B. fragilis, other Bacteroides spp., Clostridium difficile, Clostridium perfringens and Peptostreptococcus magnus, evidenced by MIC90 values of 0.5, 1, 0.25, 2 and 1mg/L, respectively. The activity of levornidazole and the comparators was poor for Veillonella spp. Generally, levornidazole displayed activity similar to or slightly higher than that of metronidazole, ornidazole and dextrornidazole against anaerobic Gram-negative bacilli, Gram-positive bacilli and Gram-positive cocci, especially B. fragilis. Favourable anti-anaerobic activity was also seen with levornidazole metabolites M1 and M4 but not M2, M3 or M5. For the 22 clinical B. fragilis strains, MBC50 and MBC90 values of levornidazole were 2mg/L and 4mg/L, respectively. Both MBC50/MIC50 and MBC90/MIC90 ratios of levornidazole were 4, similar to those of metronidazole. Levornidazole is an important anti-anaerobic option in clinical settings in terms of its potent and broad-spectrum in vitro activity, bactericidal property, and the anti-anaerobic activity of its metabolites M1 and M4. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  5. Amplified and in situ detection of redox-active metabolite using a biobased redox capacitor.

    Science.gov (United States)

    Kim, Eunkyoung; Gordonov, Tanya; Bentley, William E; Payne, Gregory F

    2013-02-19

    Redox cycling provides a mechanism to amplify electrochemical signals for analyte detection. Previous studies have shown that diverse mediators/shuttles can engage in redox-cycling reactions with a biobased redox capacitor that is fabricated by grafting redox-active catechols onto a chitosan film. Here, we report that redox cycling with this catechol-chitosan redox capacitor can amplify electrochemical signals for detecting a redox-active bacterial metabolite. Specifically, we studied the redox-active bacterial metabolite pyocyanin that is reported to be a virulence factor and signaling molecule for the opportunistic pathogen P. aeruginosa. We demonstrate that redox cycling can amplify outputs from various electrochemical methods (cyclic voltammetry, chronocoulometry, and differential pulse voltammetry) and can lower the detection limit of pyocyanin to 50 nM. Further, the compatibility of this biobased redox capacitor allows the in situ monitoring of the production of redox-active metabolites (e.g., pyocyanin) during the course of P. aeruginosa cultivation. We anticipate that the amplified output of redox-active virulence factors should permit an earlier detection of life-threatening infections by the opportunistic pathogen P. aeruginosa while the "bio-compatibility" of this measurement approach should facilitate in situ study of the spatiotemporal dynamics of bacterial redox signaling.

  6. In vitro antifungal activity of bacteria against Mycosphaerella fijiensis mediated by diffused and volatile metabolites

    Directory of Open Access Journals (Sweden)

    Mileidy Cruz-Martín

    2012-07-01

    Full Text Available Antagonistic microorganisms do not have a unique mode of action. Multiplicity of these is an important feature for selection as biological control agents. Black Sigatoka is considered the foliar disease with most economic impact for the banana industry worldwide. New strategies to control it are required to reduce the use of fungicides. That is why an increasing interest to find biological alternatives, such as the use of antagonistic bacteria, has risen. Assays wer e carr ied ou t to determine whether in v it r o ant if ungal ac ti vity of 20 bacterial str ai ns against My cosphaer ella fijiensis was caused by metabolites diffused into the culture medium or volatile. Results demonstrated that 80.0% of bacterial strains tested showed in vitro antifungal activity by diffused metabolites in the culture medium and 60.0% by producing volatile metabolites. The 55.0% of strains showed both mechanisms. This feature makes these bacteria the best candidate for its selection as biological control agent. Keywords: antagonistic, biocontrol, volatile compounds, diffused metabolites.

  7. Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristics, and treatments in the QUEST-RA study

    DEFF Research Database (Denmark)

    Sokka, Tuulikki; Toloza, Sergio; Cutolo, Maurizio

    2009-01-01

    ABSTRACT : INTRODUCTION : Gender as a predictor of outcomes of rheumatoid arthritis (RA) has evoked considerable interest over the decades. Historically, there is no consensus whether RA is worse in females or males. Recent reports suggest that females are less likely than males to achieve remiss...

  8. Secondary metabolites profiles and antioxidant activities of germinated brown and red rice

    Science.gov (United States)

    Nurnaistia, Y.; Aisyah, S.; Munawaroh, H. S. H.; Zackiyah

    2018-05-01

    The research aims to investigate the effect of germination on the secondary metabolite profiles and antioxidant activity of brown and red rice. The germination was performed by using a simple laboratory-scale machine that was designed and optimized to provide conditions that support the germination process. The germination was carried out for 2 days in dark conditions at 26°C and 99% humidity. Analysis of the secondary metabolite profile of ungerminated and germinated rice was performed using LC-MS. The antioxidant activities of ungerminated and germinated rice were done by using DPPH method. The results showed that the profiles of secondary metabolites of brown and red rice changed after germination. Some peaks were found to be induced in the germinated rice. However, some peaks were also loss during germination. The antioxidant activity of brown rice was slightly increased due to the germination, from 11.2% to 22.5%. Meanwhile the antioxidant activity of red rice was decreased after germination, from 73.8% to 60.0%.

  9. Antiviral activity of A771726, the active metabolite of leflunomide, against Junín virus.

    Science.gov (United States)

    Sepúlveda, Claudia S; García, Cybele C; Damonte, Elsa B

    2018-05-01

    The aim of this study was to investigate the effect of A771726, the active metabolite of leflunomide, (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad against the infection with Junín virus (JUNV), agent of Argentine hemorrhagic fever (AHF). The treatment with non-cytotoxic concentrations of A771726 of Vero and A549 cells infected with JUNV inhibited virus replication in a dose-dependent manner, as determined by virus yield reduction assay. The antiviral effectiveness of A771726 was not importantly affected by the multiplicity of infection and the virus strain. Moreover, the combination of A771726 and ribavirin had a significantly more potent antiviral activity than each single drug treatment. Mechanistic studies showed that the main action of A771726 is exerted before 6 h of JUNV infection. Accordingly, inhibition of viral RNA synthesis was detected in treated infected cells by real time RT-PCR. The exogenous addition of uridine or orotic acid produced a partial reversal of the inhibitory effect of A771726 on infective virus production whereas a total reversion was detected on JUNV RNA synthesis, probably by restoration of the enzymatic activity of dihydroorotate dehydrogenase (DHODH) and the intracellular pyrimidine pools. In conclusion, these results suggest that the antiviral target would be viral RNA synthesis through pyrimidine depletion, but any other effect of the compound on JUNV infection cannot be excluded. This study opens the possibility of the therapeutic application of a wide spectrum host-targeted compound alone or in combination with ribavirin to combat AHF as well as other human pathogenic arenaviruses. © 2018 Wiley Periodicals, Inc.

  10. RA reactor operation and maintenance; Pogon i odrzavanje reaktora RA

    Energy Technology Data Exchange (ETDEWEB)

    Zecevic, V [Institute of Nuclear Sciences Boris Kidric, Reaktor RA, Vinca, Beograd (Serbia and Montenegro)

    1963-02-15

    This volume includes the final report on RA reactor operation and utilization of the experimental facilities in 1962, detailed analysis of the system for heavy water distillation and calibration of the system for measuring the activity of the air.

  11. Gut Microbiota-Regulated Pharmacokinetics of Berberine and Active Metabolites in Beagle Dogs After Oral Administration.

    Science.gov (United States)

    Feng, Ru; Zhao, Zhen-Xiong; Ma, Shu-Rong; Guo, Fang; Wang, Yan; Jiang, Jian-Dong

    2018-01-01

    Berberine (BBR) is considered a multi-target drug that has significant advantages. In contrast to its significant pharmacological effects in clinic, the plasma level of BBR is very low. Our previous work revealed that dihydroberberine (dhBBR) could be an absorbable form of BBR in the intestine, and butyrate is an active metabolite that is generated by gut bacteria in rats. In this study, for the first time we describe gut microbiota-regulated pharmacokinetics in beagle dogs after oral administration of BBR by single (50 mg/kg) or multiple doses (50 mg/kg/d) for 7 days. GC-MS, GC, LC-MS/MS, and LC/MS n -IT-TOF were used to detect dhBBR, butyrate and BBR as well as its Phase I and II metabolites, respectively. The results showed that dhBBR was not detected in dog plasma but was excreted in small amounts in the feces of dogs examined on days 3 and 7. Butyrate was generated by gut bacteria and increased by 1.3- and 1.2-fold in plasma or feces, respectively, after 7 days of BBR treatment compared to the levels before treatment. Changes of intestinal bacterial composition were analyzed by 16S rRNA genes analysis. The results presented that dogs treated with BBR for 7 days increased both the abundance of the butyrate- and the nitroreductases- producing bacteria. We also identified chemical structures of the Phase I and II metabolites and analyzed their contents in beagle dogs. Eleven metabolites were detected in plasma and feces after BBR oral administration (50 mg/kg) to dogs, including 8 metabolites of Phase I and III metabolites of Phase II. The pharmacokinetic profile indicated that the concentration of BBR in plasma was low, with a C max value of 36.88 ± 23.45 ng/mL. The relative content of glucuronic acid conjugates (M11) was higher than those of other metabolites (M1, M2, M12, and M14) in plasma. BBR was detected in feces, with high excreted amounts on day 3 (2625.04 ± 1726.94 μg/g) and day 7 (2793.43 ± 488.10 μg/g). In summary, this is the first study to

  12. Activity concentrations of K, Th, Ra and radiation exposure levels in ...

    African Journals Online (AJOL)

    use

    Available online at http://www.academicjournals.org/AJEST ... average absorbed dose rate for the five quarries was found to be 541.4 nGyh-1 1m above the ground level while .... conversion factors for converting the activity concentrations of.

  13. Activation analysis of gold in geological samples (Paper No. RA-24)

    International Nuclear Information System (INIS)

    Das, N.R.; Bhattacharyya, S.N.

    1990-02-01

    The technique of neutron activation analysis (NAA) has been applied to study the distribution of gold in some geological samples. Traces of gold in the samples were preconcentrated in a solid matrix through a chemical procedure involving solvent extraction using MIBK and coprecipitation with PbS. Gold contents in the samples as determined by NAA vary from ppb to ppm levels. (author)

  14. Measurements of neutron flux in the RA reactor; Merenje karakteristika neutronskog fluksa u reaktoru RA

    Energy Technology Data Exchange (ETDEWEB)

    Raisic, N [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

    1961-12-15

    This report includes the following separate parts: Thermal neutron flux in the experimental channels od RA reactor; Epithermal neutron flux in the experimental channels od RA reactor; Fast neutron flux in the experimental channels od RA reactor; Thermal neutron flux in the thermal column and biological experimental channel; Neutronic measurements in the RA reactor cell; Temperature reactivity coefficient of the RA reactor; design of the device for measuring the activity of wire. [Serbo-Croat] Ovaj izvestaj sadrzi sledece referate: Fluks termalnih neutrona u eksperimentalnim kanalima reaktora RA; Fluks epitermalnih neutrona u eksperimentalnim kanalima reaktora RA; Fluks brzih neutrona u eksperimentalnim kanalima reaktora RA; Fluks termalnih neurona u termalnoj koloni i bioloskom eksperimentalnom kanalu; Neutronska merenja u elementarnoj celiji reaktora RA; Temperaturni koeficijent reaktivnosti reaktora RA; Projekat uredjaja za merenje radioaktivnosti zice.

  15. Radium isotope (223Ra, 224Ra, 226Ra and 228Ra) distribution near Brazil's largest port, Paranaguá Bay, Brazil

    International Nuclear Information System (INIS)

    Dias, Thais H.; Oliveira, Joselene de; Sanders, Christian J.; Carvalho, Franciane; Sanders, Luciana M.; Machado, Eunice C.; Sá, Fabian

    2016-01-01

    This work investigates the 223 Ra, 224 Ra, 226 Ra and 228 Ra isotope distribution in river, estuarine waters and sediments of the Paranaguá Estuarine Complex (PEC). The stratification of the Ra isotopes along water columns indicate differing natural sources. In sediments, the radium isotope activities was inversely proportional to the particle size. The highest concentrations of 223 Ra, 224 Ra, 226 Ra and 228 Ra in the water column were found in the bottom more saline waters and towards the inner of the estuary. These relatively high concentrations towards the bottom of the estuary may be attributed to the influence of tidally driven groundwater source and desorption from particles at the maximum turbidity zone. The apparent river water ages from the radium isotope ratios, 223 Ra/ 224 Ra and 223 Ra/ 228 Ra, indicate that the principal rivers that flow into the estuary have residence times from between 6 and 11 days. - Highlights: • Radium isotope concentrations were evaluated along a large estuarine system. • The radioactivity level in river, estuary and sediments was within a normal range. • Spatial distributions of site specific radionuclides have differing activities and sources.

  16. RA reactor operation and maintenance

    International Nuclear Information System (INIS)

    Zecevic, V.

    1963-02-01

    This volume includes the final report on RA reactor operation and utilization of the experimental facilities in 1962, detailed analysis of the system for heavy water distillation and calibration of the system for measuring the activity of the air

  17. Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST-RA database

    DEFF Research Database (Denmark)

    Sokka, T; Kautiainen, H; Pincus, T

    2009-01-01

    OBJECTIVE: To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country. METHODS: The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) cohort includes clinical....... CONCLUSIONS: The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in "low GDP" than...

  18. Mixture toxicity of the antiviral drug Tamiflu (oseltamivir ethylester) and its active metabolite oseltamivir acid

    Energy Technology Data Exchange (ETDEWEB)

    Escher, Beate I., E-mail: b.escher@uq.edu.au [University of Queensland, National Research Centre for Environmental Toxicology (Entox), 39 Kessels Rd, Brisbane, Qld 4108 (Australia); Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Duebendorf (Switzerland); Bramaz, Nadine; Lienert, Judit; Neuwoehner, Judith [Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Duebendorf (Switzerland); Straub, Juerg Oliver [F.Hoffmann-La Roche Ltd, Corporate Safety, Health and Environmental Protection, 4070 Basel (Switzerland)

    2010-02-18

    Tamiflu (oseltamivir ethylester) is an antiviral agent for the treatment of influenza A and B. The pro-drug Tamiflu is converted in the human body to the pharmacologically active metabolite, oseltamivir acid, with a yield of 75%. Oseltamivir acid is indirectly photodegradable and slowly biodegradable in sewage works and sediment/water systems. A previous environmental risk assessment has concluded that there is no bioaccumulation potential of either of the compounds. However, little was known about the ecotoxicity of the metabolite. Ester hydrolysis typically reduces the hydrophobicity and thus the toxicity of a compound. In this case, a zwitterionic, but overall neutral species is formed from the charged parent compound. If the speciation and predicted partitioning into biological membranes is considered, the metabolite may have a relevant contribution to the overall toxicity. These theoretical considerations triggered a study to investigate the toxicity of oseltamivir acid (OA), alone and in binary mixtures with its parent compound oseltamivir ethylester (OE). OE and OA were found to be baseline toxicants in the bioluminescence inhibition test with Vibrio fischeri. Their mixture effect lay between predictions for concentration addition and independent action for the mixture ratio excreted in urine and nine additional mixture ratios of OE and OA. In contrast, OE was an order of magnitude more toxic than OA towards algae, with a more pronounced effect when the direct inhibition of photosystem II was used as toxicity endpoint opposed to the 24 h growth rate endpoint. The binary mixtures in this assay yielded experimental mixture effects that agreed with predictions for independent action. This is consistent with the finding that OE exhibits slightly enhanced toxicity, while OA acts as baseline toxicant. Therefore, with respect to mixture classification, the two compounds can be considered as acting according to different modes of toxic action, although there are

  19. Stereoselective synthesis of an active metabolite of the potent PI3 kinase inhibitor PKI-179.

    Science.gov (United States)

    Chen, Zecheng; Venkatesan, Aranapakam M; Dos Santos, Osvaldo; Delos Santos, Efren; Dehnhardt, Christoph M; Ayral-Kaloustian, Semiramis; Ashcroft, Joseph; McDonald, Leonard A; Mansour, Tarek S

    2010-03-05

    The synthesis and stereochemical determination of 1-(4-(4-((1R,5R,6R)-6-hydroxy-3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-6-morpholino-1,3,5-triazin-2-yl)phenyl)-3-(pyridin-4-yl)urea (2), an active metabolite of the potent PI3 kinase inhibitor PKI-179 (1), is described. Stereospecific hydroboration of the double bond of 2,5-dihydro-1H-pyrrole 8 gave the 2,3-trans alcohol 9 exclusively. The configuration of the 3-hydroxyl group in 9 was inverted by an oxidation and stereoselective reduction sequence to give the corresponding 2,3-cis isomer 23. Both exo (21) and endo (27) isomers of the metabolite 2 were prepared via a practical synthetic route from 9 and 23, respectively, and the stereochemistry of 2 was determined to be endo. The endo isomer (27) was separated into two enantiomers 28 and 29 by chiral HPLC. Compound 2 was found to be enantiomerically pure and identical to the enantiomer 28. The absolute stereochemistry of the enantiomer 28 was determined by Mosher's method, thus establishing the stereochemistry of the active metabolite 2.

  20. Anti-Biofilm and Antivirulence Activities of Metabolites from Plectosphaerella cucumerina against Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Jinwei Zhou

    2017-05-01

    Full Text Available This study reported the efficacy of the metabolites of Plectosphaerella cucumerina, one phyllosphere fungus from Orychophragmus violaceus, against Pseudomonas aeruginosa quorum sensing (QS and QS-regulated biofilms. The minimum inhibitory concentration (MIC of the ethyl acetate (EtOAc extract from P. cucumerina against P. aeruginosa PAO1 was 1.25 mg mL−1. At sub-MIC concentrations, P. cucumerina extract (0.25–1 mg mL−1 not only inhibited biofilm formation but also disrupted preformed biofilms of P. aeruginosa PAO1 without affecting its growth. Fluorescence and scanning electron microscope (SEM showed architectural disruption of the biofilms when treated with P. cucumerina metabolites. Further investigation demonstrated that metabolites in P. cucumerina attenuated the QS-dependent virulence factors. LC-MS/MS spectra coupled with experimentally standard samples suggested that patulin and emodin might act as the principal components possessing anti-biofilm and antivirulence activities. This is the first report of (1 the isolation of P. cucumerina from the phyllosphere of O. violaceus and (2 anti-biofilm, antivirulence, and biofilm disruption activities of this fungus. Thus, this study provides fascinating new pathways for screening antipathogenic agents.

  1. Microbial transformation of (+)-nootkatone and the antiproliferative activity of its metabolites.

    Science.gov (United States)

    Gliszczyńska, Anna; Łysek, Agnieszka; Janeczko, Tomasz; Świtalska, Marta; Wietrzyk, Joanna; Wawrzeńczyk, Czesław

    2011-04-01

    Six metabolites were obtained as a result of microbial transformation of (+)-nootkatone (1) by the fungal strains: Botrytis, Didymosphaeria, Aspergillus, Chaetomium and Fusarium. Their structure were established as (+)-(4R,5S,7R,9R)-9α-hydroxynootkatone (2), (+)-(4R,5S,7R)-13-hydroxynootkatone (3) and (+)-(4R,5S,7R,9R,11S)-11,12-epoxy-9α-hydroxynootkatone (4), (+)-(4R,5S,7R,11S)-11,12-epoksynootkatone (5), (+)-(4R,5S,7R)-11,12-dihydroxynootkatone (6) and (+)-(4R,5S,7R)-7,11,12-trihydroxynootkatone (7) on the basis of their spectral data. Two products: (4) and (7) were not previously reported in the literature. The antiproliferative activity of (+)-nootkatone (1) and isolated metabolites (2-7) of its biotransformation has been evaluated. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Impact of a coal fired power plant on 226Ra activity level in sea water

    International Nuclear Information System (INIS)

    Marovic, G.; Sencar, J.

    1999-01-01

    The paper deals with radioactivity contamination originating from a coal fired power plant which, due to its location, may present a remarkable environmental problem. The plant is situated in a bay of the Adriatic close to the densely populated area with highly developed touristic activity. Its operation may cause significant damage to rich marine ecosystem characteristic for this part of the Croatian Adriatic as well as endanger urban and touristic developmental prospects of the area. Investigations of coal used in regular plant operation and of solid incombustible ash and slag showed increased natural radioactivity levels which may cause general environmental contamination of the bay as well as contamination of the marine environment of this part of the Croatian Adriatic

  3. Calculated activities of some isotopes in the RA reactor highly enriched fuel significant for possible environmental contamination - Operational report; Radni izvestaj - Proracun aktivnosti nekih izotopa u visokoobogacenom uranskom gorivu reaktora RA, znacajnih sa gledista moguce kontaminacije okoline

    Energy Technology Data Exchange (ETDEWEB)

    Bulovic, V; Martinc, R; Cupac, S [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

    1976-12-15

    This report contains calculation basis and obtained results of activities for three groups of isotopes in the RA reactor 80% enriched fuel element. The following isotopes are included: 1) {sup 85m}Kr, {sup 87}Kr, {sup 88}Kr, {sup 131}J, {sup 132}J, {sup 133}J, {sup 134}J, {sup 135}J, {sup 133}Xe, {sup 138}Xe i {sup 138}Cs, 2) {sup 89}Sr, {sup 90}Sr, {sup 91}Sr, {sup 92}Sr, {sup 95}Zr, {sup 97}Zr, {sup 103}Ru, {sup 105}Ru, {sup 106}Ru, {sup 129m}Te, {sup 134}Cs, {sup 137}Cs, {sup 140}Ba, {sup 144}Ce, kao i 3) {sup 238}Pu, {sup 239}Pu i {sup 240}Pu. It was estimated that the fuel is exposed to mean neutron flux. The periodicity of reactor operation is taken into account. Calculation results are given dependent on the time of exposure. These results are to be used as source data for Ra reactor safety analyses. [Serbo-Croat] Izlozene su osnove i prikazani su rezultati izvedenog proracuna aktivnosti tri grupe izotopa u gorivnom elementu reaktora RA sa 80% obogacenim uranom - 235. Obuhvaceni su: 1) {sup 85m}Kr, {sup 87}Kr, {sup 88}Kr, {sup 131}J, {sup 132}J, {sup 133}J, {sup 134}J, {sup 135}J, {sup 133}Xe, {sup 138}Xe i {sup 138}Cs, zatim, 2) {sup 89}Sr, {sup 90}Sr, {sup 91}Sr, {sup 92}Sr, {sup 95}Zr, {sup 97}Zr, {sup 103}Ru, {sup 105}Ru, {sup 106}Ru, {sup 129m}Te, {sup 134}Cs, {sup 137}Cs, {sup 140}Ba, {sup 144}Ce, kao i 3) {sup 238}Pu, {sup 239}Pu i {sup 240}Pu. Pretpostavljeno je da se gorivo ozracuje na srednjem fluksu neutrona, a periodicnost rada reaktora je uvazavana. Rezultati proracuna, dati u numerickom obliku, sistematizovani su kao funkcija toka vremena ozracivanja goriva. Ovi rezultati bice korisceni kao izvorni podaci kod izrade sigurnosnih analiza za reaktor RA (author)

  4. [Effective productions of plant secondary metabolites having antitumor activity by plant cell and tissue cultures].

    Science.gov (United States)

    Taniguchi, Shoko

    2005-06-01

    Methods for the effective production of plant secondary metabolites with antitumor activity using plant cell and tissue cultures were developed. The factors in tannin productivity were investigated using culture strains producing different types of hydrolyzable tannins, i.e., gallotannins (mixture of galloylglucoses), ellagi-, and dehydroellagitannins. Production of ellagi- and dehydroellagitannins was affected by the concentrations and ratio of nitrogen sources in the medium. The formation of oligomeric ellagitannins in shoots of Oenothera tetraptera was correlated with the differentiation of tissues. Cultured cells of Eriobotrya japonica producing ursane- and oleanane-type triterpenes with antitumor activities were also established.

  5. Long-Chain Metabolites of Vitamin E: Metabolic Activation as a General Concept for Lipid-Soluble Vitamins?

    Science.gov (United States)

    Schubert, Martin; Kluge, Stefan; Schmölz, Lisa; Wallert, Maria; Galli, Francesco; Birringer, Marc; Lorkowski, Stefan

    2018-01-12

    Vitamins E, A, D and K comprise the class of lipid-soluble vitamins. For vitamins A and D, a metabolic conversion of precursors to active metabolites has already been described. During the metabolism of vitamin E, the long-chain metabolites (LCMs) 13'-hydroxychromanol (13'-OH) and 13'-carboxychromanol (13'-COOH) are formed by oxidative modification of the side-chain. The occurrence of these metabolites in human serum indicates a physiological relevance. Indeed, effects of the LCMs on lipid metabolism, apoptosis, proliferation and inflammatory actions as well as tocopherol and xenobiotic metabolism have been shown. Interestingly, there are several parallels between the actions of the LCMs of vitamin E and the active metabolites of vitamin A and D. The recent findings that the LCMs exert effects different from that of their precursors support their putative role as regulatory metabolites. Hence, it could be proposed that the mode of action of the LCMs might be mediated by a mechanism similar to vitamin A and D metabolites. If the physiological relevance and this concept of action of the LCMs can be confirmed, a general concept of activation of lipid-soluble vitamins via their metabolites might be deduced.

  6. Solid-Phase Extraction of Sulfur Mustard Metabolites Using an Activated Carbon Fiber Sorbent.

    Science.gov (United States)

    Lee, Jin Young; Lee, Yong Han

    2016-01-01

    A novel solid-phase extraction method using activated carbon fiber (ACF) was developed and validated. ACF has a vast network of pores of varying sizes and microporous structures that result in rapid adsorption and selective extraction of sulfur mustard metabolites according to the pH of eluting solvents. ACF could not only selectively extract thiodiglycol and 1-methylsulfinyl-2-[2-(methylthio)-ethylsulfonyl]ethane eluting a 9:1 ratio of dichloromethane to acetone, and 1,1'-sulfonylbis[2-(methylsulfinyl)ethane] and 1,1'-sulfonylbis- [2-S-(N-acetylcysteinyl)ethane] eluting 3% hydrogen chloride in methanol, but could also eliminate most interference without loss of analytes during the loading and washing steps. A sample preparation method has been optimized for the extraction of sulfur mustard metabolites from human urine using an ACF sorbent. The newly developed extraction method was applied to the trace analysis of metabolites of sulfur mustard in human urine matrices in a confidence-building exercise for the analysis of biomedical samples provided by the Organisation for the Prohibition of Chemical Weapons. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Low Water Activity Induces the Production of Bioactive Metabolites in Halophilic and Halotolerant Fungi

    Directory of Open Access Journals (Sweden)

    Nina Gunde-Cimerman

    2010-12-01

    Full Text Available The aim of the present study was to investigate indigenous fungal communities isolated from extreme environments (hypersaline waters of solar salterns and subglacial ice, for the production of metabolic compounds with selected biological activities: hemolysis, antibacterial, and acetylcholinesterase inhibition. In their natural habitats, the selected fungi are exposed to environmental extremes, and therefore the production of bioactive metabolites was tested under both standard growth conditions for mesophilic microorganisms, and at high NaCl and sugar concentrations and low growth temperatures. The results indicate that selected halotolerant and halophilic species synthesize specific bioactive metabolites under conditions that represent stress for non-adapted species. Furthermore, adaptation at the level of the chemical nature of the solute lowering the water activity of the medium was observed. Increased salt concentrations resulted in higher hemolytic activity, particularly within species dominating the salterns. The appearance of antibacterial potential under stress conditions was seen in the similar pattern of fungal species as for hemolysis. The active extracts exclusively affected the growth of the Gram-positive bacterium tested, Bacillus subtilis. None of the extracts tested showed inhibition of acetylcholinesterase activity.

  8. Porritoxins, metabolites of Alternaria porri, as anti-tumor-promoting active compounds.

    Science.gov (United States)

    Horiuchi, Masayuki; Tokuda, Harukuni; Ohnishi, Keiichiro; Yamashita, Masakazu; Nishino, Hoyoku; Maoka, Takashi

    2006-02-01

    To search for possible cancer chemopreventive agents from natural sources, we performed primary screening of metabolites of Alternaria porri by examining their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. The ethyl acetate extract of A. porri showed the inhibitory effect on EBV-EA activation. Three porritoxins (1-3) were obtained as inhibitory active compounds for EBV-EA from ethyl acetate extract. 6-(3',3'-Dimethylallyloxy)-4-methoxy-5-methylphthalide (2) showed the strongest activity among them. Inhibitory effect of porritoxin (1) and (2) was superior to that of beta-carotene, a well-known anti-tumor promoter. Furthermore, the structure-activity correlation of porritoxins and their related compounds were discussed.

  9. Comparative evaluation of two Trichoderma harzianum strains for major secondary metabolite production and antifungal activity.

    Science.gov (United States)

    Ahluwalia, Vivek; Kumar, Jitendra; Rana, Virendra S; Sati, Om P; Walia, S

    2015-01-01

    This investigation was undertaken to identify the major secondary metabolite, produced by two Trichoderma harzianum strains (T-4 and T-5) with their antifungal activity against phytopathogenic fungi using poison food technique. The ethyl acetate extract was subjected to column chromatography using n-hexane, ethyl acetate and methanol gradually. Chromatographic separation of ethyl acetate extract of T. harzianum (T-4) resulted in the isolation and identification of palmitic acid (1), 1,8-dihydroxy-3-methylanthraquinone (2), 6-pentyl-2H-pyran-2-one (3), 2(5H)-furanone (4), stigmasterol (5) and β-sitosterol (6), while T. harzianum (T-5) gave palmitic acid (1), 1-hydroxy-3-methylanthraquinone (7), δ-decanolactone (8), 6-pentyl-2H-pyran-2-one (3), ergosterol (9), harzianopyridone (10) and 6-methyl-1,3,8-trihydroxyanthraquinone (11) as major metabolites. Among compounds screened for antifungal activity, compound 10 was found to be most active (EC50 35.9-50.2 μg mL(-1)). In conclusion, the present investigation provided significant information about antifungal activity and compounds isolated from two different strains of T. harzianum obtained from two different Himalayan locations.

  10. Activity concentrations of 238U and 226Ra in scales formed on pipes of industrial boilers in the state of Pernambuco, Brazil

    International Nuclear Information System (INIS)

    Poggi, Claudia M.B.; Farias, Emerson E.G. de; Gazineu, Maria H.P.

    2015-01-01

    The procedures employed in the industry can generate significant amounts of solid, liquid and gaseous wastes that usually contain toxic or materials of difficulty degradation. One of the facts that contribute to the formation of such wastes is the generation of steam used in operating processes and industry segments. Currently, steam supplied by boilers is the most economical and practical mode of heat transfer in industrial processes. Due to the high temperature of water used in these processes, compounds which were previously soluble become insoluble, generating residues called scales. This material, which contains stable ions, can also present naturally occurring radionuclides such as 238 U and 226 Ra, which concentrate over time in piping and equipment surfaces. If not disposed correctly, this material also can contaminate the environment. The main origin of these radionuclides is the use of groundwater in industrial processes. Thus, in regions of naturally enriched in radionuclides such as the Region of Pernambuco, including the municipalities of Paulista and Goiana, there is a greater possibility of radioactive scale formation. Therefore, this study aimed to determine the activity concentrations of 238 U and 226 Ra present in the solid wastes generated by industries situated in Paulista and Goiana, in order to assess radionuclide disequilibrium. For the sake of comparison, scale samples collected from industries located in the municipality of Caruaru, far from the previous municipalities, were also analyzed. The determination of the activity concentrations for 238 U and 226 Ra was performed by High Resolution Gamma-Ray Spectrometry. Samples were collected, prepared, packed in plastic containers and set aside for a minimum time of 21 days, for the secular equilibrium to occur between 226 Ra and its short lived descendants. The counting time was 80,000 seconds. Gamma energies used for determination of activity concentrations were 1001 keV for 238 U, and 352 ke

  11. Activity concentrations of {sup 238}U and {sup 226}Ra in scales formed on pipes of industrial boilers in the state of Pernambuco, Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Poggi, Claudia M.B.; Farias, Emerson E.G. de, E-mail: claudiapoggi04@gmail.com, E-mail: emersonemiliano@yahoo.com.br [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Departamento de Energia Nuclear; Franca, Elvis J.; Hazin, Clovis A., E-mail: chazin@cnen.gov.br [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Gazineu, Maria H.P., E-mail: helena@unicap.br [Universidade Catolica de Pernambuco (UNICAP), Recife, PE (Brazil). Centro de Ciencias e Tecnologia

    2015-07-01

    The procedures employed in the industry can generate significant amounts of solid, liquid and gaseous wastes that usually contain toxic or materials of difficulty degradation. One of the facts that contribute to the formation of such wastes is the generation of steam used in operating processes and industry segments. Currently, steam supplied by boilers is the most economical and practical mode of heat transfer in industrial processes. Due to the high temperature of water used in these processes, compounds which were previously soluble become insoluble, generating residues called scales. This material, which contains stable ions, can also present naturally occurring radionuclides such as {sup 238}U and {sup 226}Ra, which concentrate over time in piping and equipment surfaces. If not disposed correctly, this material also can contaminate the environment. The main origin of these radionuclides is the use of groundwater in industrial processes. Thus, in regions of naturally enriched in radionuclides such as the Region of Pernambuco, including the municipalities of Paulista and Goiana, there is a greater possibility of radioactive scale formation. Therefore, this study aimed to determine the activity concentrations of {sup 238}U and {sup 226}Ra present in the solid wastes generated by industries situated in Paulista and Goiana, in order to assess radionuclide disequilibrium. For the sake of comparison, scale samples collected from industries located in the municipality of Caruaru, far from the previous municipalities, were also analyzed. The determination of the activity concentrations for {sup 238}U and {sup 226}Ra was performed by High Resolution Gamma-Ray Spectrometry. Samples were collected, prepared, packed in plastic containers and set aside for a minimum time of 21 days, for the secular equilibrium to occur between {sup 226}Ra and its short lived descendants. The counting time was 80,000 seconds. Gamma energies used for determination of activity concentrations

  12. Plant/soil concentration ratios of 226Ra for contrasting sites around an active U mine-mill

    International Nuclear Information System (INIS)

    Ibrahim, S.A.; Whicker, F.W.

    1988-01-01

    Concentrations of 226Ra were determined in native vegetation and underlying substrate (soil and tailings) at various sites around a conventional open-pit, acid leach U production operation in Wyoming. Plant/soil concentration ratios (CRs) for 226Ra were estimated for various sites, including weathered tailings; a tailings impoundment shoreline; downwind from exposed tailings; a mine overburden reclamation area; and several background locations. Radium-226 concentrations for vegetation and substrate and CR values from the perturbed sites were elevated above background. The highest vegetation concentration (1.3 Bq g-1) was found in a grass which had invaded exposed, weathered tailings. Levels of 226Ra in soil and vegetation and CR values decreased with distance from the tailings impoundment edge. CR values varied significantly among sites, but few differences were found between plant species groups. The observed CR values ranged from 0.07 at the background and reclamation areas to 0.4 downwind from the tailings area. Average CR values for plants growing on exposed tailings and within one meter from the impoundment edge were 0.15 and 0.3, respectively. CR values of 226Ra for plants on tailings substrates were comparatively low in contrast to other radionuclides in the U chain. We speculate that in the case of sulfuric acid leached tailings-derived material, 226Ra is sequestered as sulfate, which is highly insoluble relative to the sulfates of the other elements (e.g., U and Th) resulting in reduced availability for plant uptake

  13. Effects of clopidogrel on the pharmacokinetics of sibutramine and its active metabolites.

    Science.gov (United States)

    Bae, Jung-Woo; Jang, Choon-Gon; Lee, Seok-Young

    2011-12-01

    Sibutramine is metabolized by the enzymes CYP2B6 and CYP2C19 into 2 active metabolites, M1 (mono-desmethyl sibutramine) and M2 (di-desmethyl sibutramine). Clopidogrel is a mechanism-based inhibitor of CYP2B6 and CYP2C19. In this study, 13 extensive metabolizers of CYP2B6 and CYP2C19 were evaluated to clarify whether clopidogrel inhibits the formation of the active metabolites of sibutramine. In the control phase, each subject received a 15-mg oral dose of sibutramine. After a washout period of 2 weeks, in the clopidogrel phase, the subjects received 300 mg of clopidogrel on the first day and then 75-mg once daily for 6 days. One hour after the last dosing of clopidogrel, all subjects received 15-mg of sibutramine. Compared with the control phase, the mean sibutramine and M1 plasma concentrations were higher after clopidogrel treatment. Clopidogrel significantly increased the half-life (242% of control phase) and area under the plasma concentration-time curve from 0 to infinity (AUC(inf)) (227% of control phase) of sibutramine and decreased the apparent oral clearance (31% of control phase) of sibutramine. Pharmacokinetic analysis showed significant increases in the AUC(inf) (162% of control phase) of M1. The CYP2B6 and CYP2C19 inhibitor clopidogrel significantly inhibited the formations of M1 from sibutramine and M2 from sibutramine by 37% and 64%, respectively. Therefore, CYP2B6 and CYP2C19 are in vivo catalysts for the formation of the 2 active metabolites of sibutramine.

  14. Antistaphylococcal activity and metabolite profiling of manuka honey (Leptospermum scoparium L.) after in vitro simulated digestion.

    Science.gov (United States)

    Mannina, Luisa; Sobolev, Anatoly P; Coppo, Erika; Di Lorenzo, Arianna; Nabavi, Seyed Mohammad; Marchese, Anna; Daglia, Maria

    2016-03-01

    The antistaphylococcal activity against methicillin-susceptible and -resistant Staphylococcus aureus and the metabolite profiling of manuka honey (MH) were investigated before and after in vitro simulated gastric (GD) and gastroduodenal (GDD) digestions. Undigested manuka honey showed antibacterial activity against all the tested strains, the GD sample showed no activity against S. aureus, and the GDD honey showed an antistaphylococcal activity, which was slightly reduced in comparison with the undigested sample. To explain these results, methylglyoxal (MGO), to which most of the antibacterial activity of MH is ascribed, was subjected to in vitro simulated GD and GDD. After digestion, MGO showed antibacterial activity at concentrations definitively higher than those registered in digested MH samples. These results showed that the antistaphylococcal activity registered after digestion cannot be ascribed to MGO. Thus metabolite analysis, carried out using an explorative untargeted NMR-based approach and a targeted RP-HPLC-PAD-ESI-MSn analysis focused on bio-active substances, was used to highlight the chemical modifications occurring from digestion. The results showed that (1) the level of MGO decreases and (2) the content of aromatic compounds, such as leptosin and methyl syringate, markers of manuka honey, was stable under gastric and gastroduodenal conditions, whereas (3) the levels of acetic and lactic acids increase in particular after gastroduodenal digestion, being 1.5 and 2.8 times higher in GDD-MH than in UND-MH, respectively. Overall, the results obtained from chemical analysis provide at least a partial explanation of the registered antibacterial activity observed after gastroduodenal digestion.

  15. Antifouling activity exhibited by secondary metabolites of the marine sponge, Haliclona exigua (Kirkpatrick)

    Digital Repository Service at National Institute of Oceanography (India)

    LimnaMol, V.P.; Raveendran, T.V.; Parameswaran, P.S.

    stream_size 29406 stream_content_type text/plain stream_name Int_Biodeterior_Biodegrad_63_67.pdf.txt stream_source_info Int_Biodeterior_Biodegrad_63_67.pdf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8... 1    Author version: Int. Biodeterior. Biodegrad.: 63(1); 2009; 67-72 Antifouling activity exhibited by secondary metabolites of the marine sponge, Haliclona exigua (Kirkpatrick) VP LIMNA MOL a , TV RAVEENDRAN a, * & PS PARAMESWARAN b a...

  16. Identification and Characterization of CINPA1 Metabolites Facilitates Structure-Activity Studies of the Constitutive Androstane Receptor

    Science.gov (United States)

    Cherian, Milu T.; Yang, Lei; Chai, Sergio C.; Lin, Wenwei

    2016-01-01

    The constitutive androstane receptor (CAR) regulates the expression of genes involved in drug metabolism and other processes. A specific inhibitor of CAR is critical for modulating constitutive CAR activity. We recently described a specific small-molecule inhibitor of CAR, CINPA1 (ethyl (5-(diethylglycyl)-10,11-dihydro-5H-dibenzo[b,f]azepin-3-yl)carbamate), which is capable of reducing CAR-mediated transcription by changing the coregulator recruitment pattern and reducing CAR occupancy at the promoter regions of its target genes. In this study, we showed that CINPA1 is converted to two main metabolites in human liver microsomes. By using cell-based reporter gene and biochemical coregulator recruitment assays, we showed that although metabolite 1 was very weak in inhibiting CAR function and disrupting CAR-coactivator interaction, metabolite 2 was inactive in this regard. Docking studies using the CAR ligand-binding domain structure showed that although CINPA1 and metabolite 1 can bind in the CAR ligand-binding pocket, metabolite 2 may be incapable of the molecular interactions required for binding. These results indicate that the metabolites of CINPA1 may not interfere with the action of CINPA1. We also used in vitro enzyme assays to identify the cytochrome P450 enzymes responsible for metabolizing CINPA1 in human liver microsomes and showed that CINPA1 was first converted to metabolite 1 by CYP3A4 and then further metabolized by CYP2D6 to metabolite 2. Identification and characterization of the metabolites of CINPA1 enabled structure-activity relationship studies of this family of small molecules and provided information to guide in vivo pharmacological studies. PMID:27519550

  17. Identification and Characterization of CINPA1 Metabolites Facilitates Structure-Activity Studies of the Constitutive Androstane Receptor.

    Science.gov (United States)

    Cherian, Milu T; Yang, Lei; Chai, Sergio C; Lin, Wenwei; Chen, Taosheng

    2016-11-01

    The constitutive androstane receptor (CAR) regulates the expression of genes involved in drug metabolism and other processes. A specific inhibitor of CAR is critical for modulating constitutive CAR activity. We recently described a specific small-molecule inhibitor of CAR, CINPA1 (ethyl (5-(diethylglycyl)-10,11-dihydro-5H-dibenzo[b,f]azepin-3-yl)carbamate), which is capable of reducing CAR-mediated transcription by changing the coregulator recruitment pattern and reducing CAR occupancy at the promoter regions of its target genes. In this study, we showed that CINPA1 is converted to two main metabolites in human liver microsomes. By using cell-based reporter gene and biochemical coregulator recruitment assays, we showed that although metabolite 1 was very weak in inhibiting CAR function and disrupting CAR-coactivator interaction, metabolite 2 was inactive in this regard. Docking studies using the CAR ligand-binding domain structure showed that although CINPA1 and metabolite 1 can bind in the CAR ligand-binding pocket, metabolite 2 may be incapable of the molecular interactions required for binding. These results indicate that the metabolites of CINPA1 may not interfere with the action of CINPA1. We also used in vitro enzyme assays to identify the cytochrome P450 enzymes responsible for metabolizing CINPA1 in human liver microsomes and showed that CINPA1 was first converted to metabolite 1 by CYP3A4 and then further metabolized by CYP2D6 to metabolite 2. Identification and characterization of the metabolites of CINPA1 enabled structure-activity relationship studies of this family of small molecules and provided information to guide in vivo pharmacological studies. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  18. {sup 226}Ra activity standardization by 4παβ(LS)-γ(NaI-Tl) anticoincidence counting

    Energy Technology Data Exchange (ETDEWEB)

    Silva, C.J. da; Poledna, R.; Santos, A.R.L.; Gomes, R.S., E-mail: carlos@ird.gov.br [Instituto de Radioproteção e Dosimetria (LNMRI/IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil). Laboratório Nacional de Metrologia das Radiações Ionizantes

    2017-07-01

    From a commercial supplier a solution containing {sup 226}Ra has been standardized at National Laboratory for Ionizing Radiation Metrology (LNMRI) for the first time using Liquid scintillation based measurement. The measurement methods are 4παβ-γ live-timed anticoincidence counting. The results obtained by anticoincidence counting were adopted as reference value and its combined uncertainty was 0.94 %. The agreement of this reference value with reference system with ionization chamber was 0.56 %. This standardization was made in order to reduce the uncertainty in {sup 226}Ra measurement in Brazil. (author)

  19. Inhibition of aromatase activity by methyl sulfonyl PCB metabolites in primary culture of human mammary fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Berg, M. van den; Heneweer, M.; Geest, M. de; Sanderson, T. [Inst. for Risk Assessment Sciences and Utrecht Univ. (Netherlands); Jong, P. de [St. Antonius Hospital, Nieuwegein (Netherlands); Bergman, A. [Stockholm Univ., Stockholm (Sweden)

    2004-09-15

    Methyl sulfonyl PCB metabolites (MeSO2-PCBs) are persistent contaminants and are ubiquitously present in humans and the environment. Lipophilicity of MeSO2- PCB metabolites is similar to the parent compounds and they have been detected in human milk, adipose, liver and lung tissue. 4- MeSO2-PCB-149 is the most abundant PCB metabolite in human adipose tissue and milk at a level of 1.5 ng/g lipids. Human blood concentration of 4-MeSO2-PCB-149 is approximately 0.03 nM. 3- MeSO2-PCB-101 is the predominant PCB metabolite in muscle and blubber in wildlife, such as otter, mink and grey seal. In the environment, they have been linked to chronic and reproductive toxicity in exposed mink. Additionaly, some MeSO{sub 2}-PCBs have been shown to be glucocorticoid receptor (GR) antagonists. Since approximately 60% of all breast tumors are estrogen responsive, exposure to compounds that are able to alter estrogen synthesis through interference with the aromatase enzyme, can lead to changes in estrogen levels and possibly to accelerated or inhibit breast tumor growth. Therefore, it is important to identify exogenous compounds that can alter aromatase activity in addition to those compounds which have direct interaction with the estrogen receptor (ER). Aromatase (CYP19) comprises the ubiquitous flavoprotein, NADPH-cytochrome P450 reductase, and a unique cytochrome P450 that is exclusively expressed in estrogen producing cells. Previous studies have revealed that expression of the aromatase gene is regulated in a species- and tissue specific manner. In healthy breast tissue, the predominantly active aromatase promoter region I.4 is regulated by glucocorticoids and class I cytokines. Therefore, it is important to investigate possible aromatase inhibiting properties of MeSO{sub 2}-PCBs (as anti glucocorticoids?) in relevant human tissues. We used primary human mammary fibroblasts because of their role in breast cancer development. We compared the results in primary fibroblasts with

  20. Changes in hand bone mineral density and the association with the level of disease activity in patients with RA

    NARCIS (Netherlands)

    Dirven, L.; Guler-Yuksel, M.; de Beus, W.M.; Ronday, H.K.; Speyer, I.; Huizinga, T.W.; Dijkmans, B.A.C.; Allaart, C.F.; Lems, W.F.

    2011-01-01

    Objective. To determine if metacarpal bone mineral density (mBMD) gain occurs in patients with rheumatoid arthritis (RA). If mBMD loss is driven by inflammation, we expect to find mBMD gain in patients who are in remission. Methods. mBMD was measured by digital X-ray radiogrammetry in consecutive

  1. Thiopurine methyltransferase genotype-phenotype discordance and thiopurine active metabolite formation in childhood acute lymphoblastic leukaemia.

    Science.gov (United States)

    Lennard, Lynne; Cartwright, Cher Suzanne; Wade, Rachel; Richards, Susan M; Vora, Ajay

    2013-07-01

    In children with acute lymphoblastic leukaemia (ALL) bone marrow activity can influence red blood cell (RBC) kinetics, the surrogate tissue for thiopurine methyltransferase (TPMT) measurements. The aim of this study was to investigate TPMT phenotype-genotype concordance in ALL, and the influence of TPMT on thiopurine metabolite formation. We measured TPMT (activity, as units ml(-1) packed RBCs and genotype) at diagnosis (n = 1150) and TPMT and thioguanine nucleotide (TGN) and methylmercaptopurine nucleotide (MeMPN) metabolites (pmol/8 × 10(8) RBCs) during chemotherapy (n = 1131) in children randomized to thioguanine or mercaptopurine on the United Kingdom trial ALL97. Median TPMT activity at diagnosis (8.5 units) was significantly lower than during chemotherapy (13.8 units, median difference 5.1 units, 95% confidence interval (CI) 4.8, 5.4, P mercaptopurine, median TGNs were higher in TPMT heterozygous genotype (754 pmol) than wild-type (360 pmol) patients (median difference 406 pmol, 95% CI 332, 478, P products of the TPMT reaction, were higher in wild-type (10 650 pmol) than heterozygous patients (3868 pmol) (P < 0.0001). In TPMT intermediate activity patients with a wild-type genotype, TGN (median 366 pmol) and MeMPN (median 8590 pmol) concentrations were similar to those in wild-type, high activity patients. In childhood ALL, TPMT activity should not be used to predict heterozygosity particularly in blood samples obtained at disease diagnosis. Genotype is a better predictor of TGN accumulation during chemotherapy. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  2. Thiopurine methyltransferase genotype–phenotype discordance and thiopurine active metabolite formation in childhood acute lymphoblastic leukaemia

    Science.gov (United States)

    Lennard, Lynne; Cartwright, Cher Suzanne; Wade, Rachel; Richards, Susan M; Vora, Ajay

    2013-01-01

    Aims In children with acute lymphoblastic leukaemia (ALL) bone marrow activity can influence red blood cell (RBC) kinetics, the surrogate tissue for thiopurine methyltransferase (TPMT) measurements. The aim of this study was to investigate TPMT phenotype–genotype concordance in ALL, and the influence of TPMT on thiopurine metabolite formation. Methods We measured TPMT (activity, as units ml−1 packed RBCs and genotype) at diagnosis (n = 1150) and TPMT and thioguanine nucleotide (TGN) and methylmercaptopurine nucleotide (MeMPN) metabolites (pmol/8 × 108 RBCs) during chemotherapy (n = 1131) in children randomized to thioguanine or mercaptopurine on the United Kingdom trial ALL97. Results Median TPMT activity at diagnosis (8.5 units) was significantly lower than during chemotherapy (13.8 units, median difference 5.1 units, 95% confidence interval (CI) 4.8, 5.4, P mercaptopurine, median TGNs were higher in TPMT heterozygous genotype (754 pmol) than wild-type (360 pmol) patients (median difference 406 pmol, 95% CI 332, 478, P products of the TPMT reaction, were higher in wild-type (10 650 pmol) than heterozygous patients (3868 pmol) (P < 0.0001). In TPMT intermediate activity patients with a wild-type genotype, TGN (median 366 pmol) and MeMPN (median 8590 pmol) concentrations were similar to those in wild-type, high activity patients. Conclusions In childhood ALL, TPMT activity should not be used to predict heterozygosity particularly in blood samples obtained at disease diagnosis. Genotype is a better predictor of TGN accumulation during chemotherapy. PMID:23252716

  3. Citrus fruits as a treasure trove of active natural metabolites that potentially provide benefits for human health.

    Science.gov (United States)

    Lv, Xinmiao; Zhao, Siyu; Ning, Zhangchi; Zeng, Honglian; Shu, Yisong; Tao, Ou; Xiao, Cheng; Lu, Cheng; Liu, Yuanyan

    2015-01-01

    Citrus fruits, which are cultivated worldwide, have been recognized as some of the most high-consumption fruits in terms of energy, nutrients and health supplements. What is more, a number of these fruits have been used as traditional medicinal herbs to cure diseases in several Asian countries. Numerous studies have focused on Citrus secondary metabolites as well as bioactivities and have been intended to develop new chemotherapeutic or complementary medicine in recent decades. Citrus-derived secondary metabolites, including flavonoids, alkaloids, limonoids, coumarins, carotenoids, phenolic acids and essential oils, are of vital importance to human health due to their active properties. These characteristics include anti-oxidative, anti-inflammatory, anti-cancer, as well as cardiovascular protective effects, neuroprotective effects, etc. This review summarizes the global distribution and taxonomy, numerous secondary metabolites and bioactivities of Citrus fruits to provide a reference for further study. Flavonoids as characteristic bioactive metabolites in Citrus fruits are mainly introduced.

  4. Biotransformation of Bisphenol AF to Its Major Glucuronide Metabolite Reduces Estrogenic Activity

    Science.gov (United States)

    Yin, Jie; Zhang, Jing; Feng, Yixing; Shao, Bing

    2013-01-01

    Bisphenol AF (BPAF), an endocrine disrupting chemical, can induce estrogenic activity through binding to estrogen receptor (ER). However, the metabolism of BPAF in vivo and the estrogenic activity of its metabolites remain unknown. In the present study, we identified four metabolites including BPAF diglucuronide, BPAF glucuronide (BPAF-G), BPAF glucuronide dehydrated and BPAF sulfate in the urine of Sprague-Dawley (SD) rats. BPAF-G was further characterized by nuclear magnetic resonance (NMR). After treatment with a single dose of BPAF, BPAF was metabolized rapidly to BPAF-G, as detected in the plasma of SD rats. Biotransformation of BPAF to BPAF-G was confirmed with human liver microsomes (HLM), and Vmax of glucuronidation for HLM was 11.6 nmol/min/mg. We also found that BPAF glucuronidation could be mediated through several human recombinant UDP-glucuronosyltransferases (UGTs) including UGT1A1, UGT1A3, UGT1A8, UGT1A9, UGT2B4, UGT2B7, UGT2B15 and UGT2B17, among which UGT2B7 showed the highest efficiency of glucuronidation. To explain the biological function of BPAF biotransformation, the estrogenic activities of BPAF and BPAF-G were evaluated in ER-positive breast cancer T47D and MCF7 cells. BPAF significantly stimulates ER-regulated gene expression and cell proliferation at the dose of 100 nM and 1 μM in breast cancer cells. However, BPAF-G did not show any induction of estrogenic activity at the same dosages, implying that formation of BPAF-G is a potential host defense mechanism against BPAF. Based on our study, biotransformation of BPAF to BPAF-G can eliminate BPAF-induced estrogenic activity, which is therefore considered as reducing the potential threat to human beings. PMID:24349450

  5. A preliminary study on 226Ra, 232Th, 40K and 137Cs activity concentrations in vegetables and fruits frequently consumed by inhabitants of Elazig Region, Turkey

    International Nuclear Information System (INIS)

    Cumhur Canbazoglu; Mahmut Dogru

    2013-01-01

    Determining radioactivity levels in foodstuffs is of great importance for the protection of human health. In addition, the literature includes few studies related to this subject in Turkey. In this study, gamma spectroscopic system was used in order to measure 226 Ra, 232 Th, 40 K and 137 Cs activity concentrations in vegetables and fruits produced in Elazig( Region. The average activity concentrations in vegetables was calculated as 0.64 ± 0.26 Bq kg -1 for 226 Ra, 0.65 ± 0.14 Bq kg -1 for 232 Th, 13.98 ± 1.22 Bq kg -1 for 40 K, and 0.54 ± 0.04 Bq kg -1 for 137 Cs. The average activity concentrations in fruits were 1.52 ± 0.34, 0.98 ± 0.23, 18.66 ± 1.13 and 0.59 ± 0.16 Bq kg -1 , respectively for 226 Ra, 232 Th, 40 K and 137 Cs. Total committed effective dose value was determined as 20 and 30.55 μSv y -1 , respectively for vegetables and fruits. The findings were compared with previous data reported for Turkey and other regions of the world. (author)

  6. In-stream attenuation of neuro-active pharmaceuticals and their metabolites

    Science.gov (United States)

    Writer, Jeffrey; Antweiler, Ronald C.; Ferrar, Imma; Ryan, Joseph N.; Thurman, Michael

    2013-01-01

    In-stream attenuation was determined for 14 neuro-active pharmaceuticals and associated metabolites. Lagrangian sampling, which follows a parcel of water as it moves downstream, was used to link hydrological and chemical transformation processes. Wastewater loading of neuro-active compounds varied considerably over a span of several hours, and thus a sampling regime was used to verify that the Lagrangian parcel was being sampled and a mechanism was developed to correct measured concentrations if it was not. In-stream attenuation over the 5.4-km evaluated reach could be modeled as pseudo-first-order decay for 11 of the 14 evaluated neuro-active pharmaceutical compounds, illustrating the capacity of streams to reduce conveyance of neuro-active compounds downstream. Fluoxetine and N-desmethyl citalopram were the most rapidly attenuated compounds (t1/2 = 3.6 ± 0.3 h, 4.0 ± 0.2 h, respectively). Lamotrigine, 10,11,-dihydro-10,11,-dihydroxy-carbamazepine, and carbamazepine were the most persistent (t1/2 = 12 ± 2.0 h, 12 ± 2.6 h, 21 ± 4.5 h, respectively). Parent compounds (e.g., buproprion, carbamazepine, lamotrigine) generally were more persistent relative to their metabolites. Several compounds (citalopram, venlafaxine, O-desmethyl-venlafaxine) were not attenuated. It was postulated that the primary mechanism of removal for these compounds was interaction with bed sediments and stream biofilms, based on measured concentrations in stream biofilms and a column experiment using stream sediments.

  7. 226 Ra in food

    International Nuclear Information System (INIS)

    Toader, M.

    1993-01-01

    Between 1986 and 1992 the author has evaluated natural levels of 226 Ra in some foods representing the major components of the diet in Bucharest population. The estimated daily intake by an adult was 72.5 mBq 226 Ra/day or 65.9 mBq 226 Ra/g.Ca. (Author)

  8. Research nuclear reactor RA - Annual Report 1989

    International Nuclear Information System (INIS)

    Sotic, O.

    1989-12-01

    Annual report concerning the project 'RA research nuclear reactor' for 1989, financed by the Serbian ministry of science is divided into two parts. First part is concerned with RA reactor operation and maintenance, which is the task of the Division for reactor engineering of the Institute for multidisciplinary studies and RA reactor engineering. Second part deals with radiation protection activities at the RA reactor which is the responsibility of the Institute for radiation protection. Scientific council of the Institute for multidisciplinary studies and RA reactor engineering has stated that this report describes adequately the activity and tasks fulfilled at the RA reactor in 1989. The scope and the quality of the work done were considered successful both concerning the maintenance and reconstruction, as well as radiation protection activities [sr

  9. RA Research nuclear reactor - Annual report 1987

    International Nuclear Information System (INIS)

    1987-12-01

    Annual report concerning the project 'RA research nuclear reactor' for 1987, financed by the Serbian ministry of science is divided into two parts. First part is concerned with RA reactor operation and maintenance, which is the task of the Division for reactor engineering of the Institute for multidisciplinary studies and RA reactor engineering. Second part deals with radiation protection activities at the RA reactor which is the responsibility of the Institute for radiation protection. Scientific council of the Institute for multidisciplinary studies and RA reactor engineering has stated that this report describes adequately the activity and tasks fulfilled at the RA reactor in 1989. The scope and the quality of the work done were considered successful both concerning the maintenance and reconstruction, as well as radiation protection activities [sr

  10. RA Research reactor, Annual report 1988

    International Nuclear Information System (INIS)

    Sotic, O.

    1988-12-01

    Annual report concerning the project 'RA research nuclear reactor' for 1989, financed by the Serbian ministry of science is divided into two parts. First part is concerned with RA reactor operation and maintenance, which is the task of the Division for reactor engineering of the Institute for multidisciplinary studies and RA reactor engineering. Second part deals with radiation protection activities at the RA reactor which is the responsibility of the Institute for radiation protection. Scientific council of the Institute for multidisciplinary studies and RA reactor engineering has stated that this report describes adequately the activity and tasks fulfilled at the RA reactor in 1989. The scope and the quality of the work done were considered successful both concerning the maintenance and reconstruction, as well as radiation protection activities [sr

  11. Antimicrobial activity of extracellular metabolites from antagonistic bacteria isolated from potato (Solanum phureja crops

    Directory of Open Access Journals (Sweden)

    Sinar David Granada García

    2014-09-01

    Full Text Available Microorganisms for biological control are capable of producing active compounds that inhibit the development of phytopathogens, constituting a promising tool toob tain active principles that could replace synthetic pesticides. This study evaluatedtheability of severalpotentialbiocontrol microorganismsto produce active extracellular metabolites. In vitro antagonistic capability of 50 bacterial isolates from rhizospheric soils of "criolla" potato (Solanum phureja was tested through dual culture in this plant with different plant pathogenic fungi and bacteria. Isolates that showed significantly higher antagonistic activity were fermented in liquid media and crude extracts from the supernatants had their biological activities assessed by optical density techniques. Inhibitory effecton tested pathogens was observed for concentrations between 0.5% and 1% of crude extracts. There was a correlation between the antimicrobial activity of extracts and the use of nutrient-rich media in bacteria fermentation. Using a bioguided method, a peptidic compound, active against Fusarium oxysporum, was obtained from the 7ANT04 strain (Pyrobaculum sp.. Analysis by nuclear magnetic resonance and liquid chromatography coupled to mass detector evidenced an 11-amino acid compound. Bioinformatic software using raw mass data confirmed the presence of a cyclic peptide conformed by 11 mostly non-standard amino acids.

  12. Evaluation of Ra-226, Th-232 and K-40 activities concentrations and radium equivalent index in several Brazilian economic wall paints

    International Nuclear Information System (INIS)

    Fonseca, Leandro M.; Pecequilo, Brigitte R.S.

    2015-01-01

    The titanium dioxide used as the white pigment in paints is produced from the processing of ilmenite minerals. As monazite, the main ilmenite radioactive contaminant, contains 1 to 20% thorium dioxide and also some uranium traces, so, eventually, wall paints can contain radioactivity. Activity concentrations of the naturally occurring radionuclides 226 Ra, 232 Th and 40 K were determined in 15 Brazilian economic wall paints samples, by high resolution gamma-ray spectrometry. The activities concentrations in the studied samples ranged from 1.3 ± 0.2 Bq/kg to 23.4 ± 0.7 Bq/kg for 226 Ra; from 2.5 ± 0.4 Bq/kg to 45.8 ± 1.5 Bq/kg for 232 Th and from 5.8 ± 2.1 Bq/kg to 157 ± 22 Bq/kg for 40 K. The radium equivalent index, calculated from the 226 Ra, 232 Th and 40 K concentrations, varied from 1.30 Bq/kg up to 95.9 Bq/kg, below the value of 370 Bq/kg recommended by OECD for a safety use in residential building applications. (author)

  13. Activity of the Service for maintenance of the electronic equipment of the RA reactor in 1976, report - Annex IV

    International Nuclear Information System (INIS)

    Milosevic, M.

    1976-01-01

    Within the organizational structure of the RA reactor staff, the Service for instrumentation maintenance has the following tasks: maintenance of the existing electronic equipment; participating in experiments planning and preparation of electronic equipment; purchasing new equipment, spare parts and components; construction of new equipment for internal needs; implementation of new equipment. Basic instrumentation of the reactor facility includes: control and protection system, and dosimetry system [sr

  14. Activity of the RA Reactor Physics group in 1980 - Definition of the Operation conditions for future safe and economical RA reactor operation with 80% enriched fuel; Prilog Ia - Rad sluzbe za fiziku reaktora RA u 1980. godini - Definisanje pogonskih uslova za dalji siguran i ekonomican rad reaktora RA sa 80% obogacenim gorivom

    Energy Technology Data Exchange (ETDEWEB)

    Martinc, R [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

    1980-12-15

    During 1980. the RA reactor was not in operation. That is why this period was devoted to definition of operating conditions for further reactor operation with 80% enriched fuel. The fuel elements which were in the core at the moment of shutdown in March 1979will not be used again (388 80% enriched fuel elements, and 511 2% enriched fuel elements). The reactor will be operated only with 80% enriched fuel, staring with initiat core configuration with 440 elements on the borders gradually changing to equi;librium core with 720 fuel elements. The analyses were concerned with safety issues of future operation. [Serbo-Croat] Reaktor RA tokom 1980 godine nije radio. Zbog toga je ovaj period iskoriscen za intenzivan rad na definisanju pogonskih uslova za dalji rad reaktora sa 80% obogacenim gorivom. Gorivo sa kojim je reaktor prestao da radi marta 1979. godine (388 gorivnih elemenata 80% obogacenoh i 511 elementa 2% obogaceno) nece biti vraceno u jezgro, vec ce reaktor raditi samo sa 80% obogacenim gorivom, pocev od konfiguracije sa 440 elemenata na periferiji do ravnotezne konfiguracije sa 720 elemenata. Sve nalize su se bavile sigurnosnim aspektima rada reaktora sa visokoobogacenim gorivom u jezgru.

  15. The active metabolite of leflunomide, A77 1726, protects rat hepatocytes against bile acid-induced apoptosis.

    NARCIS (Netherlands)

    Vrenken, T.E.; Buist-Homan, M.; Kalsbeek, A.J.; Faber, K.N.; Moshage, H.J.

    2008-01-01

    BACKGROUND/AIMS: Leflunomide is used in the treatment of autoimmune diseases as an anti-inflammatory agent. Leflunomide and its active metabolite A77 1726 modulate mitogen-activated protein kinases (MAPK), Src kinases, the phosphoinositide-3 kinase (PI3K)/Akt-pathway and nuclear factor (NF)-kappaB

  16. The active metabolite of leflunomide, A77 1726, protects rat hepatocytes against bile acid-induced apoptosis

    NARCIS (Netherlands)

    Vrenken, Titia E.; Buist-Homan, Manon; Kalsbeek, Allard Jan; Faber, Klaas Nico; Moshage, Han

    Background/Aims: Leflunomide is used in the treatment of autoimmune diseases as an anti-inflammatory agent. Leflunomide and its active metabolite A77 1726 modulate mitogen-activated protein kinases (MAPK), Src kinases, the phosphoinositide-3 kinase (PI3K)/Akt-pathway and nuclear factor (NF)-kappa B

  17. Determination of 226Ra and 228Ra in surface seawater around Sagami bay and its vicinity

    International Nuclear Information System (INIS)

    Nakano-Ohta, T.; Kubota, T.; Mahara, Y.; Yoshikawa, M.; Sato, J.

    2006-01-01

    Activity ratios of 228 Ra/ 226 Ra in surface seawaters were observed at 5 ports of Izu-Oshima, Ajiro port of Sagami bay and Umizuri park of Tokyo bay. The 228 Ra/ 226 Ra activity ratio in surface seawaters were from 0.2 to 0.7 for Izu-Oshima, from 0.2 to 0.7 for Ajiro port and from 0.6 to 0.8 for Tokyo bay. The activity ratio in surface seawaters of Izu-Oshima and Atami of Sagami bay showed lower in spring and highly in autumn, while narrow variation pattern was observed in Umizuri park of Tokyo bay. The observed variation patterns of 228 Ra/ 226 Ra in surface seawaters at Izu-oshima, Ajiro park and Umizuri park may be reflected by difference of contribution from amount of seawater far off coast with low 228 Ra concentration. (author)

  18. Shared care or nurse consultations as an alternative to rheumatologist follow-up for rheumatoid arthritis (RA) outpatients with stable low disease-activity RA: cost-effectiveness based on a 2-year randomized trial.

    Science.gov (United States)

    Sørensen, J; Primdahl, J; Horn, H C; Hørslev-Petersen, K

    2015-01-01

    To compare the cost-effectiveness of three types of follow-up for outpatients with stable low-activity rheumatoid arthritis (RA). In total, 287 patients were randomized to either planned rheumatologist consultations, shared care without planned consultations, or planned nurse consultations. Effectiveness measures included disease activity (Disease Activity Score based on 28 joint counts and C-reactive protein, DAS28-CRP), functional status (Health Assessment Questionnaire, HAQ), and health-related quality of life (EuroQol EQ-5D). Cost measures included activities in outpatient clinics and general practice, prescription and non-prescription medicine, dietary supplements, other health-care resources, and complementary and alternative care. Measures of effectiveness and costs were collected by self-reported questionnaires at inclusion and after 12 and 24 months. Incremental cost-effectiveness rates (ICERs) were estimated in comparison with rheumatologist consultations. Changes in disease activity, functional status, and health-related quality of life were not statistically significantly different for the three groups, although the mean scores were better for the shared care and nurse care groups compared with the rheumatologist group. Shared care and nurse care were non-significantly less costly than rheumatologist care. As both shared care and nurse care were associated with slightly better EQ-5D improvements and lower costs, they dominated rheumatologist care. At EUR 10,000 per quality-adjusted life year (QALY) threshold, shared care and nurse care were cost-effective with more than 90% probability. Nurse care was cost-effective in comparison with shared care with 75% probability. Shared care and nurse care seem to cost less but provide broadly similar health outcomes compared with rheumatologist outpatient care. However, it is still uncertain whether nurse care and shared care are cost-effective in comparison with rheumatologist outpatient care.

  19. Secondary metabolites from Sida rhombifolia L. (Malvaceae) and the vasorelaxant activity of cryptolepinone.

    Science.gov (United States)

    Chaves, Otemberg Souza; Gomes, Roosevelt Albuquerque; Tomaz, Anna Cláudia de Andrade; Fernandes, Marianne Guedes; das Graças Mendes, Leônidas; de Fátima Agra, Maria; Braga, Valdir Andrade; de Fátima Vanderlei de Souza, Maria

    2013-03-01

    The phytochemical study of Sida rhombifolia L. (Malvaceae) led to the isolation through chromatographic techniques of eleven secondary metabolites: sitosterol (1a) and stigmasterol (1b), sitosterol-3-O-b-D-glucopyranoside (2a) and stigmasterol-3-O-b-D-glucopyranoside (2b), phaeophytin A (3), 17³-ethoxypheophorbide A (4), 13²-hydroxy phaeophytin B (5), 17³-ethoxypheophorbide B (6), 5,7-dihydroxy-4'-methoxyflavone (7), cryptolepinone (8) and a salt of cryptolepine (9). Their structures were identified by ¹H- and ¹³C-NMR using one- and two-dimensional techniques. In addition, the vasorelaxant activity of cryptolepinone in rat mesenteric artery rings is reported herein for the first time.

  20. Secondary Metabolites from Sida rhombifolia L. (Malvaceae and the Vasorelaxant Activity of Cryptolepinone

    Directory of Open Access Journals (Sweden)

    Maria de Fátima Vanderlei de Souza

    2013-03-01

    Full Text Available The phytochemical study of Sida rhombifolia L. (Malvaceae led to the isolation through chromatographic techniques of eleven secondary metabolites: sitosterol (1a and stigmasterol (1b, sitosterol-3-O-b-D-glucopyranoside (2a and stigmasterol-3-O-b-D-glucopyranoside (2b, phaeophytin A (3, 173-ethoxypheophorbide A (4, 132-hydroxy phaeophytin B (5, 173-ethoxypheophorbide B (6, 5,7-dihydroxy-4'-methoxyflavone (7, cryptolepinone (8 and a salt of cryptolepine (9. Their structures were identified by 1H- and 13C-NMR using one- and two-dimensional techniques. In addition, the vasorelaxant activity of cryptolepinone in rat mesenteric artery rings is reported herein for the first time.

  1. Secondary Metabolites from the Marine-Derived Fungus Dichotomomyces sp. L-8 and Their Cytotoxic Activity

    Directory of Open Access Journals (Sweden)

    Li-Hong Huang

    2017-03-01

    Full Text Available Bioassay-guided isolation of the secondary metabolites from the fungus Dichotomomyces sp. L-8 associated with the soft coral Lobophytum crassum led to the discovery of two new compounds, dichotones A and B (1 and 2, together with four known compounds including dichotocejpin C (3, bis-N-norgliovictin (4, bassiatin (5 and (3R,6R-bassiatin (6. The structures of these compounds were determined by 1D, 2D NMR and mass spectrometry. (3R,6R-bassiatin (6 displayed significant cytotoxic activities against the human breast cancer cell line MDA-MB-435 and the human lung cancer cell line Calu3 with IC50 values of 7.34 ± 0.20 and 14.54 ± 0.01 μM, respectively, while bassiatin (5, the diastereomer of compound 6, was not cytotoxic.

  2. Suppression of SOS-inducing activity of chemical mutagens by metabolites from microbial transformation of (-)-isolongifolene.

    Science.gov (United States)

    Sakata, Kazuki; Oda, Yoshimitsu; Miyazawa, Mitsuo

    2010-02-24

    In this study, biotransformation of (-)-isolongifolene (1) by Glomerella cingulata and suppressive effect on umuC gene expression by chemical mutagens 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (furylfuramide) and aflatoxin B(1) (AFB(1)) of the SOS response in Salmonella typhimurium TA1535/pSK1002 were investigated. Initially, 1 was carried out the microbial transformation by G. cingulata. The result found that 1 was converted into (-)-isolongifolen-9-one (2), (-)-(2S)-13-hydroxy-isolongifolen-9-one (3), and (-)-(4R)-4-hydroxy-isolongifolen-9-one (4) by G. cingulata, and their conversion rates were 60, 25, and 15%, respectively. The metabolites suppressed the SOS-inducing activity of furylfuramid and AFB(1) in the umu test. Comound 2 showed gene expression by chemical mutagens furylfuramide and AFB(1) was suppressed 54 and 50% at <0.5 mM, respectively. Compound 2 is the most effective compound in this experiment.

  3. Metabolites from roots of Colubrina greggii var. yucatanensis and evaluation of their antiprotozoan, cytotoxic and antiproliferative activities

    International Nuclear Information System (INIS)

    Dominguez-Carmona, Dafne B.; Escalante-Erosa, Fabiola; Garcia-Sosa, Karlina; Pena-Rodriguez, Luis M.

    2011-01-01

    Purification of the root extract of Colubrina greggii var. yucatanensis resulted in the isolation and identification of 3-O-acetyl ceanothic acid as a new natural ceanothane triterpene, together with the known metabolites ceanothic acid, cenothenic acid, betulinic acid, discarine B and chrysophanein. The natural products and the semisynthetic esters acetyl dimethyl ceanothate, dimethyl ceanothate and chrysophanein peracetate showed moderate to low leishmanicidal and trypanocidal activities. None of the metabolites showed cytotoxic or antiproliferative effects. The results also suggested that betulinic acid contributes to the antiplasmodial activity originally detected in the crude root extract of C. greggii var. yucatanensis. (author)

  4. Metabolites from roots of Colubrina greggii var. yucatanensis and evaluation of their antiprotozoan, cytotoxic and antiproliferative activities

    Energy Technology Data Exchange (ETDEWEB)

    Dominguez-Carmona, Dafne B.; Escalante-Erosa, Fabiola; Garcia-Sosa, Karlina; Pena-Rodriguez, Luis M., E-mail: lmanuel@cicy.m [Centro de Investigacion Cientifica de Yucatan (Mexico). Unidad de Biotecnologia; Ruiz-Pinell, Grace; Gutierrez-Yapu, David; Gimenez-Turba, Alberto [Universidad Mayor de San Andres, La Paz (Bolivia, Plurinational State of). Inst. de Investigaciones Farmaco-Bioquimicas; Chan-Bacab, Manuel J. [Universidad Autonoma de Campeche (Mexico). Dept. de Microbiologia Ambiental y Biotecnologia; Moo-Puc, Rosa E. [Centro Medico Ignacio Garcia Tellez, Col. Industrial, Merida, Yucatan (Mexico). Unidad de Investigacion Medica Yucatan y Unidad Medica de Alta Especialidad; Veitch, Nigel C. [Jodrell Laboratory, Richmond, Surrey (United Kingdom)

    2011-07-01

    Purification of the root extract of Colubrina greggii var. yucatanensis resulted in the isolation and identification of 3-O-acetyl ceanothic acid as a new natural ceanothane triterpene, together with the known metabolites ceanothic acid, cenothenic acid, betulinic acid, discarine B and chrysophanein. The natural products and the semisynthetic esters acetyl dimethyl ceanothate, dimethyl ceanothate and chrysophanein peracetate showed moderate to low leishmanicidal and trypanocidal activities. None of the metabolites showed cytotoxic or antiproliferative effects. The results also suggested that betulinic acid contributes to the antiplasmodial activity originally detected in the crude root extract of C. greggii var. yucatanensis. (author)

  5. Mapping the spatial distribution and activity of "2"2"6Ra at legacy sites through Machine Learning interpretation of gamma-ray spectrometry data

    International Nuclear Information System (INIS)

    Varley, Adam; Tyler, Andrew; Smith, Leslie; Dale, Paul; Davies, Mike

    2016-01-01

    Radium ("2"2"6Ra) contamination derived from military, industrial, and pharmaceutical products can be found at a number of historical sites across the world posing a risk to human health. The analysis of spectral data derived using gamma-ray spectrometry can offer a powerful tool to rapidly estimate and map the activity, depth, and lateral distribution of "2"2"6Ra contamination covering an extensive area. Subsequently, reliable risk assessments can be developed for individual sites in a fraction of the timeframe compared to traditional labour-intensive sampling techniques: for example soil coring. However, local heterogeneity of the natural background, statistical counting uncertainty, and non-linear source response are confounding problems associated with gamma-ray spectral analysis. This is particularly challenging, when attempting to deal with enhanced concentrations of a naturally occurring radionuclide such as "2"2"6Ra. As a result, conventional surveys tend to attribute the highest activities to the largest total signal received by a detector (Gross counts): an assumption that tends to neglect higher activities at depth. To overcome these limitations, a methodology was developed making use of Monte Carlo simulations, Principal Component Analysis and Machine Learning based algorithms to derive depth and activity estimates for "2"2"6Ra contamination. The approach was applied on spectra taken using two gamma-ray detectors (Lanthanum Bromide and Sodium Iodide), with the aim of identifying an optimised combination of detector and spectral processing routine. It was confirmed that, through a combination of Neural Networks and Lanthanum Bromide, the most accurate depth and activity estimates could be found. The advantage of the method was demonstrated by mapping depth and activity estimates at a case study site in Scotland. There the method identified significantly higher activity ( 0.4 m), that conventional gross counting algorithms failed to identify. It was

  6. Mapping the spatial distribution and activity of {sup 226}Ra at legacy sites through Machine Learning interpretation of gamma-ray spectrometry data

    Energy Technology Data Exchange (ETDEWEB)

    Varley, Adam, E-mail: a.l.varley@stir.ac.uk [Department of Biological and Environmental Sciences, University of Stirling, Stirling FK9 4LA (United Kingdom); Tyler, Andrew [Department of Biological and Environmental Sciences, University of Stirling, Stirling FK9 4LA (United Kingdom); Smith, Leslie [Department of Computing Science and Mathematics, University of Stirling, Stirling FK9 4LA (United Kingdom); Dale, Paul [Scottish Environmental Protection Agency, Radioactive Substances, Strathallan House, Castle Business Park, Stirling FK9 4TZ (United Kingdom); Davies, Mike [Nuvia Limited, The Library, Eight Street, Harwell Oxford, Didcot, Oxfordshire OX11 0RL (United Kingdom)

    2016-03-01

    Radium ({sup 226}Ra) contamination derived from military, industrial, and pharmaceutical products can be found at a number of historical sites across the world posing a risk to human health. The analysis of spectral data derived using gamma-ray spectrometry can offer a powerful tool to rapidly estimate and map the activity, depth, and lateral distribution of {sup 226}Ra contamination covering an extensive area. Subsequently, reliable risk assessments can be developed for individual sites in a fraction of the timeframe compared to traditional labour-intensive sampling techniques: for example soil coring. However, local heterogeneity of the natural background, statistical counting uncertainty, and non-linear source response are confounding problems associated with gamma-ray spectral analysis. This is particularly challenging, when attempting to deal with enhanced concentrations of a naturally occurring radionuclide such as {sup 226}Ra. As a result, conventional surveys tend to attribute the highest activities to the largest total signal received by a detector (Gross counts): an assumption that tends to neglect higher activities at depth. To overcome these limitations, a methodology was developed making use of Monte Carlo simulations, Principal Component Analysis and Machine Learning based algorithms to derive depth and activity estimates for {sup 226}Ra contamination. The approach was applied on spectra taken using two gamma-ray detectors (Lanthanum Bromide and Sodium Iodide), with the aim of identifying an optimised combination of detector and spectral processing routine. It was confirmed that, through a combination of Neural Networks and Lanthanum Bromide, the most accurate depth and activity estimates could be found. The advantage of the method was demonstrated by mapping depth and activity estimates at a case study site in Scotland. There the method identified significantly higher activity (< 3 Bq g{sup −1}) occurring at depth (> 0.4 m), that conventional gross

  7. Raman spectroscopy applied to identify metabolites in urine of physically active subjects.

    Science.gov (United States)

    Moreira, Letícia Parada; Silveira, Landulfo; da Silva, Alexandre Galvão; Fernandes, Adriana Barrinha; Pacheco, Marcos Tadeu Tavares; Rocco, Débora Dias Ferraretto Moura

    2017-11-01

    Raman spectroscopy is a rapid and non-destructive technique suitable for biological fluids analysis. In this work, dispersive Raman spectroscopy has been employed as a rapid and nondestructive technique to detect the metabolites in urine of physically active subjects before and after vigorous 30min pedaling or running compared to sedentary subjects. For so, urine samples from 9 subjects were obtained before and immediately after physical activities and submitted to Raman spectroscopy (830nm excitation, 250mW laser power, 20s integration time) and compared to urine from 5 sedentary subjects. The Raman spectra of urine from sedentary showed peaks related to urea, creatinine, ketone bodies, phosphate and other nitrogenous compounds. These metabolic biomarkers presented peaks with different intensities in the urine of physically active individuals after exercises compared to before, measured by the intensity of selected peaks the Raman spectra, which means different concentrations after training. These peaks presented different intensity values for each subject before physical activity, also behaving differently compared to the post-training: some subjects presented increase while others decrease the intensity. Raman spectroscopy may allow the development of a rapid and non-destructive test for metabolic evaluation of the physical training in active and trained subjects using urine samples, allowing nutrition adjustment with the sport's performance. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Yellow-Cedar, Callitropsis (Chamaecyparis) nootkatensis, Secondary Metabolites, Biological Activities, and Chemical Ecology.

    Science.gov (United States)

    Karchesy, Joseph J; Kelsey, Rick G; González-Hernández, M P

    2018-05-01

    Yellow-cedar, Callitropsis nootkatensis, is prevalent in coastal forests of southeast Alaska, western Canada, and inland forests along the Cascades to northern California, USA. These trees have few microbial or animal pests, attributable in part to the distinct groups of biologically active secondary metabolites their tissues store for chemical defense. Here we summarize the new yellow-cedar compounds identified and their biological activities, plus new or expanded activities for tissues, extracts, essential oils and previously known compounds since the last review more than 40 years ago. Monoterpene hydrocarbons are the most abundant compounds in foliage, while heartwood contains substantial quantities of oxygenated monoterpenes and oxygenated sesquiterpenes, with one or more tropolones. Diterpenes occur in foliage and bark, whereas condensed tannins have been isolated from inner bark. Biological activities expressed by one or more compounds in these groups include fungicide, bactericide, sporicide, acaricide, insecticide, general cytotoxicity, antioxidant and human anticancer. The diversity of organisms impacted by whole tissues, essential oils, extracts, or individual compounds now encompasses ticks, fleas, termites, ants, mosquitoes, bacteria, a water mold, fungi and browsing animals. Nootkatone, is a heartwood component with sufficient activity against arthropods to warrant research focused toward potential development as a commercial repellent and biopesticide for ticks, mosquitoes and possibly other arthropods that vector human and animal pathogens.

  9. Neuropharmacological and neuroprotective activities of some metabolites produced by cell suspension culture of Waltheria americana Linn.

    Science.gov (United States)

    Mundo, Jorge; Villeda-Hernández, Juana; Herrera-Ruiz, Maribel; Gutiérrez, María Del Carmen; Arellano-García, Jesús; León-Rivera, Ismael; Perea-Arango, Irene

    2017-10-01

    Waltheria americana is a plant used in Mexican traditional medicine to treat some nervous system disorders. The aims of the present study were to isolate and determine the neuropharmacological and neurprotective activities of metabolites produced by a cell suspension culture of Waltheria americana. Submerged cultivation of W. americana cells provided biomass. A methanol-soluble extract (WAsc) was obtained from biomass. WAsc was fractionated yielding the chromatographic fractions 4WAsc-H 2 O and WAsc-CH 2 Cl 2 . For the determination of anticonvulsant activity in vivo, seizures were induced in mice by pentylenetetrazol (PTZ). Neuropharmacological activities (release of gamma amino butyric acid (GABA) and neuroprotection) of chromatographic fractions were determined by in vitro histological analysis of brain sections of mice post mortem. Fraction 4WAsc-H 2 O (containing saccharides) did not produce neuronal damage, neurodegeneration, interstitial tissue edema, astrocytic activation, nor cell death. Pretreatment of animals with 4WAsc-H 2 O and WAsc-CH 2 Cl 2 from W. americana cell suspensions induced an increase in: GABA release, seizure latency, survival time, neuroprotection, and a decrease in the degree of severity of tonic/tonic-clonic convulsions, preventing PTZ-induced death of up to 100% of animals of study. Bioactive compounds produced in suspension cell culture of W. americana produce neuroprotective and neuropharmacological activities associated with the GABAergic neurotransmission system. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Automated measurement of 224Ra and 226Ra in water

    International Nuclear Information System (INIS)

    Dimova, N.; Burnett, W.C.; Horwitz, E.P.; Lane-Smith, D.

    2007-01-01

    We present a new simple approach for automated, non-destructive measurement of the alpha-emitting radium isotopes ( 223 Ra, 224 Ra, and 226 Ra) in water based on the emanation of their respective radon daughters ( 219 Rn, 220 Rn, and 222 Rn). The method combines the high adsorption uptake of MnO 2 Resin for radium (K d =2.4x10 4 ml/g) over a wide pH range with the simplicity of the activity registration using a commercial radon-in-air analyzer (RAD7, DURRIDGE Company, Inc). Radium is first adsorbed onto the MnO 2 Resin by passing a water sample through the resin packed in a gas-tight glass cartridge. The same cartridge is then connected to the radon analyzer via a simple tubing system to circulate air through the resin and a drying system. The efficiency of the proposed system is determined by running standards prepared in the same manner. Our results indicate that the efficiency for 226 Ra is >22% if both 218 Po and 214 Po counts are collected. This is comparable with typical efficiencies for alpha spectrometry but with much less sample preparation. We estimate that an MDA of 0.8 pCi/L for 226 Ra may be obtained with this new approach using a 1 L water sample and less than 4 h of counting

  11. Measurements of neutron flux in the RA reactor

    International Nuclear Information System (INIS)

    Raisic, N.

    1961-12-01

    This report includes the following separate parts: Thermal neutron flux in the experimental channels od RA reactor; Epithermal neutron flux in the experimental channels od RA reactor; Fast neutron flux in the experimental channels od RA reactor; Thermal neutron flux in the thermal column and biological experimental channel; Neutronic measurements in the RA reactor cell; Temperature reactivity coefficient of the RA reactor; design of the device for measuring the activity of wire [sr

  12. Antiproliferative, Antibacterial and Antifungal Activity of the Lichen Xanthoria parietina and Its Secondary Metabolite Parietin

    Directory of Open Access Journals (Sweden)

    Adriana Basile

    2015-04-01

    Full Text Available Lichens are valuable natural resources used for centuries throughout the world as medicine, food, fodder, perfume, spices and dyes, as well as for other miscellaneous purposes. This study investigates the antiproliferative, antibacterial and antifungal activity of the acetone extract of the lichen Xanthoria parietina (Linnaeus Theodor Fries and its major secondary metabolite, parietin. The extract and parietin were tested for antimicrobial activity against nine American Type Culture Collection standard and clinically isolated bacterial strains, and three fungal strains. Both showed strong antibacterial activity against all bacterial strains and matched clinical isolates, particularly against Staphylococcus aureus from standard and clinical sources. Among the fungi tested, Rhizoctonia solani was the most sensitive. The antiproliferative effects of the extract and parietin were also investigated in human breast cancer cells. The extract inhibited proliferation and induced apoptosis, both effects being accompanied by modulation of expression of cell cycle regulating genes such as p16, p27, cyclin D1 and cyclin A. It also mediated apoptosis by activating extrinsic and intrinsic cell death pathways, modulating Tumor Necrosis Factor-related apoptosis-inducing ligand (TRAIL and B-cell lymphoma 2 (Bcl-2, and inducing Bcl-2-associated agonist of cell death (BAD phosphorylation. Our results indicate that Xanthoria parietina is a major potential source of antimicrobial and anticancer substances.

  13. Determination of the four natural Ra isotopes in thermal waters by gamma-ray spectrometry

    International Nuclear Information System (INIS)

    Condomines, M.; Rihs, S.; Lloret, E.; Seidel, J.L.

    2010-01-01

    Our method for the simultaneous determination of the four natural Ra isotopes ( 226 Ra, 228 Ra, 224 Ra and 223 Ra) in thermal waters involves a separation of Ra on a selective filter (3 M EMPORE TM Radium Rad disk), and a single counting using a broad-energy HPGe detector (BE Ge manufactured by CANBERRA TM ). The calculation of 223 Ra and 228 Ra activities requires interference and cascade summing corrections. The 226 Ra activities in CO 2 -rich thermal waters of the Lodeve Basin (South of France) range from 530 to 2240 mBq/l. The low ( 228 Ra/ 226 Ra) activity ratios (0.19-0.29) suggest that Ra is mostly derived from the aquifer carbonates. The short-lived 224 Ra and 223 Ra are probably added to the water through recoil or desorption processes from Th-enriched coatings on the fracture walls.

  14. Characterizing Dissolved Organic Matter and Metabolites in an Actively Serpentinizing Ophiolite Using Global Metabolomics Techniques

    Science.gov (United States)

    Seyler, L. M.; Rempfert, K. R.; Kraus, E. A.; Spear, J. R.; Templeton, A. S.; Schrenk, M. O.

    2017-12-01

    Environmental metabolomics is an emerging approach used to study ecosystem properties. Through bioinformatic comparisons to metagenomic data sets, metabolomics can be used to study microbial adaptations and responses to varying environmental conditions. Since the techniques are highly parallel to organic geochemistry approaches, metabolomics can also provide insight into biogeochemical processes. These analyses are a reflection of metabolic potential and intersection with other organisms and environmental components. Here, we used an untargeted metabolomics approach to characterize dissolved organic carbon and aqueous metabolites from groundwater obtained from an actively serpentinizing habitat. Serpentinites are known to support microbial communities that feed off of the products of serpentinization (such as methane and H2 gas), while adapted to harsh environmental conditions such as high pH and low DIC availability. However, the biochemistry of microbial populations that inhabit these environments are understudied and are complicated by overlapping biotic and abiotic processes. The aim of this study was to identify potential sources of carbon in an environment that is depleted of soluble inorganic carbon, and to characterize the flow of metabolites and describe overlapping biogenic and abiogenic processes impacting carbon cycling in serpentinizing rocks. We applied untargeted metabolomics techniques to groundwater taken from a series of wells drilled into the Semail Ophiolite in Oman.. Samples were analyzed via quadrupole time-of-flight liquid chromatography tandem mass spectrometry (QToF-LC/MS/MS). Metabolomes and metagenomic data were imported into Progenesis QI software for statistical analysis and correlation, and metabolic networks constructed using the Genome-Linked Application for Metabolic Maps (GLAMM), a web interface tool. Further multivariate statistical analyses and quality control was performed using EZinfo. Pools of dissolved organic carbon could

  15. Assessment of the oestrogenic activity of the contraceptive progestin levonorgestrel and its non-phenolic metabolites.

    Science.gov (United States)

    Santillán, R; Pérez-Palacios, G; Reyes, M; Damián-Matsumura, P; García, G A; Grillasca, I; Lemus, A E

    2001-09-14

    Levonorgestrel (13beta-ethyl-17alpha-ethynyl-17beta-hydroxy-4-gonen-3-one), a potent contraceptive progestin stimulates growth and proliferation of cultured breast cancer cells through a receptor-mediated mechanism, even though levonorgestrel does not bind to the oestrogen receptor (ER). To assess whether the oestrogen-like effects induced by this synthetic progestin are exerted via its metabolic conversion products, we studied the binding affinity of three A-ring levonorgestrel derivatives to the ER and their capability to transactivate an oestrogen-dependent yeast system co-transfected with the human ER gene and oestrogen responsive elements fused to a beta-galactosidase reporter vector. The results demonstrated that the 3beta,5alpha reduced levonorgestrel derivative and to a lesser extent its 3alpha isomer interact with the oestrogen receptor, with a significantly lower relative binding affinity (2.4% and 0.4%, respectively) than that of oestradiol (100%), while levonorgestrel does not. Both levonorgestrel metabolites were able to activate, in a dose-dependent manner, the beta-galactosidase reporter gene in the yeast expression system, an effect that was precluded by a steroidal antioestrogen. The oestrogenic potency of levonorgestrel metabolites was significantly lower (750-fold) than that of oestradiol. Furthermore, high doses of 3beta,5alpha levonorgestrel (2.5 mg/day/6 days) induced an increase of oestrogen-dependent progestin receptor in the anterior pituitary of castrated rats. The overall data offer a plausible explanation for the weak oestrogenic effects induced by high, non-pharmacological doses of levonorgestrel.

  16. Equol, a Dietary Daidzein Gut Metabolite Attenuates Microglial Activation and Potentiates Neuroprotection In Vitro

    Directory of Open Access Journals (Sweden)

    Lalita Subedi

    2017-02-01

    Full Text Available Estrogen deficiency has been well characterized in inflammatory disorders including neuroinflammation. Daidzein, a dietary alternative phytoestrogen found in soy (Glycine max as primary isoflavones, possess anti‐inflammatory activity, but the effect of its active metabolite Equol (7‐hydroxy‐3‐(4′‐hydroxyphenyl‐chroman has not been well established. In this study, we investigated the anti‐neuroinflammatory and neuroprotective effect of Equol in vitro. To evaluate the potential effects of Equol, three major types of central nervous system (CNS cells, including microglia (BV‐2, astrocytes (C6, and neurons (N2a, were used. Effects of Equol on the expression of inducible nitric oxide synthase (iNOS, cyclooxygenase (COX‐2, Mitogen activated protein kinase (MAPK signaling proteins, and apoptosis‐related proteins were measured by western blot analysis. Equol inhibited the lipopolysaccharide (LPS‐induced TLR4 activation, MAPK activation, NF‐kB‐mediated transcription of inflammatory mediators, production of nitric oxide (NO, release of prostaglandin E2 (PGE‐2, secretion of tumor necrosis factor‐α (TNF‐α and interleukin 6 (IL‐6, in Lipopolysaccharide (LPS‐activated murine microglia cells. Additionally, Equol protects neurons from neuroinflammatory injury mediated by LPS‐activated microglia through downregulation of neuronal apoptosis, increased neurite outgrowth in N2a cell and neurotrophins like nerve growth factor (NGF production through astrocytes further supporting its neuroprotective potential. These findings provide novel insight into the anti‐neuroinflammatory effects of Equol on microglial cells, which may have clinical significance in cases of neurodegeneration.

  17. Ticagrelor, but not clopidogrel active metabolite, displays antithrombotic properties in the left atrial endocardium.

    Science.gov (United States)

    Reiner, Martin F; Breitenstein, Alexander; Holy, Erik W; Glanzmann, Martina; Amstalden, Heidi; Stämpfli, Simon F; Bonetti, Nicole R; Falk, Volkmar; Keller, Stephan; Savarese, Gianluigi; Benussi, Stefano; Maisano, Francesco; Lüscher, Thomas F; Beer, Jürg H; Steffel, Jan; Camici, Giovanni G

    2017-03-21

    Oral anticoagulation is considered standard therapy for stroke prevention in atrial fibrillation (AF). Endocardial activation triggers expression of pro-thrombotic mediators including tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1), and contributes to thrombus formation in the left atrial appendage (LAA) of AF patients. Recently, pleiotropic effects of specific P2Y12 receptor antagonists were demonstrated; however, whether these drugs possess antithrombotic effects on LAA endocardial cells currently remains unknown. LAA were obtained from 14 patients with known AF undergoing elective cardiac surgery including LAA removal at the University Hospital Zurich. LAA endocardial cells were isolated and pre-incubated with ticagrelor (10-7, 10-6, 10-5M) or clopidogrel active metabolite (CAM) (1.5 × 10-8, 1.5 × 10-7, 1.5 × 10-6 M) before stimulation with tumour necrosis factor-alpha (TNF-α) (10 ng/mL). Finally, TF and PAI-1 expression and activity were analysed. Ticagrelor, unlike CAM, concentration dependently decreased TNF-α-induced TF expression and TF activity in LAA endocardial cells. Further, ticagrelor, but not CAM reduced PAI-1 expression and enzyme activity in TNF-α-stimulated LAA endocardial cells. In contrast, TF pathway inhibitor (TFPI) remained unaffected by both dugs. Ticagrelor, but not CAM, reduces expression and activity of TF and PAI-1 in LAA endocardial cells isolated from patients with AF, indicating possible local antithrombotic effects. Such pleiotropic properties of ticagrelor may contribute to a reduction in thromboembolic complications in patients with AF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  18. The oxygen-centered radicals scavenging activity of sulfasalazine and its metabolites. A direct protection of the bowel.

    Science.gov (United States)

    Prónai, L; Yukinobu, I; Láng, I; Fehér, J

    1992-01-01

    Oxygen-centered radicals, such as superoxide (O2-) and hydroxyl radicals (.OH) generated by phagocytes have been suggested to be involved in the pathogenesis of chronic inflammations of the bowel, such as Crohn's disease and colitis ulcerosa. Recently, sulfasalazine (SASP) and its metabolites have been reported to exert their effects as a direct scavenger of oxygen-centered radicals in the bowel. To scavenge oxygen-centered radicals in vivo, however, SASP and its metabolites have to react with O2- and/or .OH in vitro very rapidly, furthermore they have to reach an appropriate (possible millimolar) concentration range at the site of inflammation. To test this possibility, we investigated the direct O2- and .OH scavenging activity of SASP and its metabolites using the specific electron paramagnetic resonance/spin trapping method, and we compared the 50% inhibition rates of SASP and its metabolites with their known concentrations in the bowel and in the human plasma. It was found that SASP and its metabolites, such as 5-amino-salicylic acid (5-ASA), and acetyl-5-amino-salicylic acid (AC-5-ASA), but not sulfapyridine (SP) and acetyl-sulfapyridine (Ac-SP) have a direct O2- and .OH scavenging activity in vitro systems. Among the compounds, SASP and 5-ASA can reach a concentration which is appropriate to scavenge oxygen-centered radicals in the bowel but not in the human plasma. It was concluded that the in vivo antiinflammatory effects of SASP and its metabolites are, at least partly, due to the direct oxygen-centered scavenging activity of these drugs.

  19. Identification and quantification of bio-actives and metabolites in physiological matrices by automated HPLC-MS

    NARCIS (Netherlands)

    van Platerink, C.J.

    2010-01-01

    Identification and quantification of bio-actives and metabolites in physiological matrices by automated HPLC-MS > Food plays an important role in human health. Nowadays there is an increasing interest in the health effects of so-calles functional foods, e.g. effects on blood pressure, cholesterol

  20. Insights into the mechanisms of Promysalin, a secondary metabolite with genus-specific antibacterial activity against Pseudomonas

    Science.gov (United States)

    Promysalin, a secondary metabolite produced by Pseudomonas putida RW10S1, has antibacterial activity against a wide variety of Pseudomonas sp., including both human and plant pathogens. Promysalin induces swarming and biofilm formation in the producing species, and inhibits growth of susceptible sp...

  1. Determination of 226 Ra and 228 Ra in mineral spring waters of the Aguas da Prata region

    International Nuclear Information System (INIS)

    Oliveira, J. de.

    1993-01-01

    Concentration levels of 226 Ra and 228 Ra have been analysed in most of the mineral spring waters available in the Aguas da Prata region. The 226 Ra and 228 Ra were determined by coprecipitation with barium sulphate. The 226 Ra was determined by gross alpha counting of the Ba(Ra)SO 4 precipitate. The determination of 228 Ra was done by measuring the gross beta activity of the same precipitate. Both measurements were carried out in a low background gas flow proportional counter. Dose calculations were performed in order to evaluate the relative importance of such radionuclides to the radiation exposure due to the ingestion of these waters. Based upon measured concentrations, committed effective doses up to 5.5 x 10 -1 mSv/y and 1.0 x 10 -2 mSv/y were observed for 226 Ra and 228 Ra, respectively. These results show that 226 Ra is the main contributor to radiation exposure. (author)

  2. Antibacterial activity and characterization of secondary metabolites isolated from mangrove plant Avicennia officinalis

    Institute of Scientific and Technical Information of China (English)

    Valentin Bhimba B; J Meenupriya; Elsa Lycias Joel; D Edaya Naveena; Suman kumar; M Thangaraj

    2010-01-01

    Objective:To explore antibacterial activity and characterization of secondary metabolites isolated from mangrove plant Avicennia officinalis (A. officinalis). Methods:In the present study the leaf extracts of A. officinalis were examined for its antibacterial potential using five different solvents against some reference strains of human pathogenic bacteria for the crude extract. Maximum activity was observed for ethyl acetate and hence different concentrations like 15μL, 25μL, and 50μL of ethyl extracts was checked for its antibacterial activity. Partial purification of crude extract was carried by column chromatography and fractions were analyzed using gas chromatography-mass spectrometry (GC-MS) to identify compounds. Results:The crude ethyl acetate extracts of A. officinalis showed remarkable antibacterial activity with zones of inhibition of 13 mm against Eschericia coli (E. coli) and 11 mm against Staphylococcus aureus (S. aureus). Fraction 13 (ethyl acetate÷methanol=8÷2) as the most potent one against with the minimal inhibitory concentration of 30 mm against E. coli and 25 mm against S. aureus. The GC-MS resultsof active column fraction (F13) revealed that the active principals were a mixture of hydroxy-4 methoxybenzoic acid, diethyl phthalate, oleic acid. Conclusions:The leaf extracts with proven antibacterial effects can clearly be directed towards cancer treatment as to inhibiting cancer cell growth. The limited number of test organisms owes to a constraint of resource. So, the effect of strong bursts of leaf extracts on human pathogenic bacteria should further be tested on a wide range of test organisms.

  3. Anti-rheumatoid Activity of Secondary Metabolites Produced by Endophytic Chaetomium globosum

    Science.gov (United States)

    Abdel-Azeem, Ahmed M.; Zaki, Sherif M.; Khalil, Waleed F.; Makhlouf, Noha A.; Farghaly, Lamiaa M.

    2016-01-01

    The aim of the present study was to investigate the anti-rheumatoid activity of secondary metabolites produced by endophytic mycobiota in Egypt. A total of 27 endophytic fungi were isolated from 10 dominant medicinal plant host species in Wadi Tala, Saint Katherine Protectorate, arid Sinai, Egypt. Of those taxa, seven isolates of Chaetomium globosum (CG1–CG7), being the most frequent taxon, were recovered from seven different host plants and screened for production of active anti-inflammatory metabolites. Isolates were cultivated on half – strength potato dextrose broth for 21 days at 28°C on a rotatory shaker at 180 rpm, and extracted in ethyl acetate and methanol, respectively. The probable inhibitory effects of both extracts against an adjuvant induced arthritis (AIA) rat model were examined and compared with the effects of methotrexate (MTX) as a standard disease-modifying anti-rheumatoid drug. Disease activity and mobility scoring of AIA, histopathology and transmission electron microscopy (TEM) were used to evaluate probable inhibitory roles. A significant reduction (P < 0.05) in the severity of arthritis was observed in both the methanolic extract of CG6 (MCG6) and MTX treatment groups 6 days after treatment commenced. The average arthritis score of the MCG6 treatment group was (10.7 ± 0.82) compared to (13.8 ± 0.98) in the positive control group. The mobility score of the MCG6 treatment group (1.50 ± 0.55) was significantly lower than that of the positive control group (3.33 ± 0.82). In contrast, the ethyl acetate extract of CG6 (EACG6) treatment group showed no improvements in arthritis and mobility scores in AIA model rats. Histopathology and TEM findings confirmed the observation. Isolate CG6 was subjected to sequencing for confirmation of phenotypic identification. The internal transcribed spacer (ITS) 1–5.8 s – ITS2 rDNA sequences obtained were compared with those deposited in the GenBank Database and registered with accession number KC

  4. Activities needed for exploitation of the RA reactor I-IV, Part III, IZ-093-0103-1961; Radovi za potrebe eksploatacije raktora RA - I-IV - III deo, IZ-093-0103-1961

    Energy Technology Data Exchange (ETDEWEB)

    Jurida, V [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

    1961-12-15

    For the purpose of designing the low-temperature loop at the RA reactor, a list of materials that would be irradiated in the reactor was made. This document includes a review of the radiochemistry data for the listed materials and data about thermal stability of the mentioned materials. Calculation of heat generated in listed samples was based on the theoretical and experimental results of radiation characteristics of the RA reactor. Maximum temperature values in the samples without forced cooling are calculated. [Serbo-Croat] Za potrebe projektovanja niskotemperaturne petlje na reaktoru RA nacinjen je pregled materijala za ozracivanje u reaktoru. Ovaj dokument sadrzi pregled radiajaciono hemijskih podataka za navedene materijale i podatke o termickoj stabilnosti pomenutih materijala. Toplota generisana u navedenim uzorcima racunata je uzimajuci u obzir osnovne podatke teorijske i eksperimentalne rezultate odredjivanja karakteristika zracenja u reaktoru. Izracunate su maksimalne temperature u uzorcima bez prinudnog hladjenja.

  5. Metabolites related to renal function, immune activation, and carbamylation are associated with muscle composition in older adults.

    Science.gov (United States)

    Lustgarten, Michael S; Fielding, Roger A

    2017-12-15

    Reduced skeletal muscle density in older adults is associated with insulin resistance, decreased physical function, and an increased all-cause mortality risk. To elucidate mechanisms that may underlie the maintenance of skeletal muscle density, we conducted a secondary analysis of previously published muscle composition and serum metabolomic data in 73 older adults (average age, 78y). Multivariable-adjusted linear regression was used to examine associations between 321 metabolites with muscle composition, defined as the ratio between normal density (NDM) with low density (LDM) thigh muscle cross sectional area (NDM/LDM). Sixty metabolites were significantly (p≤0.05 and qMetabolites that were significantly associated with muscle composition were then tested for their association with circulating markers of renal function (blood urea nitrogen, creatinine, uric acid), and with the immune response (neutrophils/lymphocytes) and activation (kynurenine/tryptophan). 43 significant NDM/LDM metabolites (including urea) were co-associated with at least 1 marker of renal function; 23 of these metabolites have been previously identified as uremic solutes. The neutrophil/lymphocyte ratio was significantly associated with NDM/LDM (β±SE: -0.3±0.1, p=0.01, q=0.04). 35 significant NDM/LDM metabolites were co-associated with immune activation. Carbamylation (defined as homocitrulline/lysine) was identified as a pathway that may link renal function and immune activation with muscle composition, as 29 significant NDM/LDM metabolites were co-associated with homocitrulline/lysine, with at least 2 markers of renal function, and with kynurenine/tryptophan. When considering that elevated urea and uremic metabolites have been linked with an increased systemic microbial burden, that antimicrobial defense can be reduced in the presence of carbamylation, and that adipocytes can promote host defense, we propose the novel hypothesis that the age-related increase in adipogenesis within muscle

  6. Microbial communication leading to the activation of silent fungal secondary metabolite gene clusters

    Directory of Open Access Journals (Sweden)

    Tina eNetzker

    2015-04-01

    Full Text Available Microorganisms form diverse multispecies communities in various ecosystems. The high abundance of fungal and bacterial species in these consortia results in specific communication between the microorganisms. A key role in this communication is played by secondary metabolites (SMs, which are also called natural products. Recently, it was shown that interspecies ‘talk’ between microorganisms represents a physiological trigger to activate silent gene clusters leading to the formation of novel SMs by the involved species. This review focuses on mixed microbial cultivation, mainly between bacteria and fungi, with a special emphasis on the induced formation of fungal SMs in co-cultures. In addition, the role of chromatin remodeling in the induction is examined, and methodical perspectives for the analysis of natural products are presented. As an example for an intermicrobial interaction elucidated at the molecular level, we discuss the specific interaction between the filamentous fungi Aspergillus nidulans and Aspergillus fumigatus with the soil bacterium Streptomyces rapamycinicus, which provides an excellent model system to enlighten molecular concepts behind regulatory mechanisms and will pave the way to a novel avenue of drug discovery through targeted activation of silent SM gene clusters through co-cultivations of microorganisms.

  7. Measurements of U and Ra Activities in Drinking Water Samples and of Rn in Dwellings in Morocco. Calculation of Equivalent Effective Doses

    International Nuclear Information System (INIS)

    Choukri, A.; Hakam, O.K.

    2013-01-01

    Activities of uranium and radium isotopes were measured in some drinking water samples collected from wells, springs and tap water samples. The obtained results show that the 238 U activity, is relatively higher in wells than in springs and 226 Ra activity is more higher in hot springs. The results are similar to those published for other non polluting regions of the world and don't present any risk for public health in Morocco. In parallel measurements of indoor radon showed that the calculated effective dose for dwellings are comparable to those obtained in other regions in the word. The risks related to these activities could be avoided by simple precautions such the continuous ventilation.

  8. Respiratory activity and browning of minimally processed sweet potatoes Atividade respiratória e escurecimento de raízes de batata-doce minimamente processada

    Directory of Open Access Journals (Sweden)

    Celso L. Moretti

    2002-09-01

    Full Text Available Sweet potatoes (Ipomoea batatas L., 'Brazlândia Roxa', 'Brazlândia Branca' and 'Princesa' were harvested at optimum maturity to evaluate respiratory activity and browning susceptibility of minimally processed roots. After harvest, non-blemished roots were graded for size (18±2cm and diameter (5±1cm, and minimally processed inside a cold room. Processed roots were placed in sealed glass jars and stored at 3±0.5°C to evaluate respiratory activity during a 4-hour period or were packed in plastic films with partial vacuum to evaluate development of browning. Packages were stored under refrigerated conditions (3±0.5°C for 5 days. Daily, minimally processed roots were evaluated for browning according to a scale ranging from 0 (extremely browned to 5 (no browning and using an objective assay (absorbance at 340 nm. Minimally processed roots showed a pronounced increase in carbon dioxide evolution immediately after processing. 'Princesa' had the highest respiratory activity among the evaluated cultivars, being 40% higher two hours after processing than the other cultivars. 'Brazlândia Roxa' and 'Brazlândia Branca' were significantly less susceptible to browning compared to 'Princesa', which was rated as unacceptable for commercial use at the end of the storage period. 'Brazlândia Roxa' and 'Brazlândia Branca' were still marketable at the end of the storage period.Batata doce (Ipomoea batatas L., 'Brazlândia Roxa', 'Brazlândia Branca' e 'Princesa' foram colhidas no ponto ótimo de maturidade hortícola, com o objetivo de avaliar-se a atividade respiratória e a suscetibilidade ao escurecimento de raízes minimamente processadas. Após a colheita, raízes sem danos mecânicos aparentes foram selecionadas para tamanho (18±2cm e diâmetro (5±1cm e foram minimamente processadas no interior de uma câmara fria. As raízes minimamente processadas foram colocadas em frascos de vidro hermeticamente fechados e armazenados a 3±0,5°C para avaliar

  9. An invasive plant promotes its arbuscular mycorrhizal symbioses and competitiveness through its secondary metabolites: indirect evidence from activated carbon.

    Directory of Open Access Journals (Sweden)

    Yongge Yuan

    Full Text Available Secondary metabolites released by invasive plants can increase their competitive ability by affecting native plants, herbivores, and pathogens at the invaded land. Whether these secondary metabolites affect the invasive plant itself, directly or indirectly through microorganisms, however, has not been well documented. Here we tested whether activated carbon (AC, a well-known absorbent for secondary metabolites, affect arbuscular mycorrhizal (AM symbioses and competitive ability in an invasive plant. We conducted three experiments (experiments 1-3 with the invasive forb Solidago canadensis and the native Kummerowia striata. Experiment 1 determined whether AC altered soil properties, levels of the main secondary metabolites in the soil, plant growth, and AMF communities associated with S. canadensis and K. striata. Experiment 2 determined whether AC affected colonization of S. canadensis by five AMF, which were added to sterilized soil. Experiment 3 determined the competitive ability of S. canadensis in the presence and absence of AMF and AC. In experiment 1, AC greatly decreased the concentrations of the main secondary metabolites in soil, and the changes in concentrations were closely related with the changes of AMF in S. canadensis roots. In experiment 2, AC inhibited the AMF Glomus versiforme and G. geosporum but promoted G. mosseae and G. diaphanum in the soil and also in S. canadensis roots. In experiment 3, AC reduced S. canadensis competitive ability in the presence but not in the absence of AMF. Our results provided indirect evidence that the secondary metabolites (which can be absorbed by AC of the invasive plant S. canadensis may promote S. canadensis competitiveness by enhancing its own AMF symbionts.

  10. An invasive plant promotes its arbuscular mycorrhizal symbioses and competitiveness through its secondary metabolites: indirect evidence from activated carbon.

    Science.gov (United States)

    Yuan, Yongge; Tang, Jianjun; Leng, Dong; Hu, Shuijin; Yong, Jean W H; Chen, Xin

    2014-01-01

    Secondary metabolites released by invasive plants can increase their competitive ability by affecting native plants, herbivores, and pathogens at the invaded land. Whether these secondary metabolites affect the invasive plant itself, directly or indirectly through microorganisms, however, has not been well documented. Here we tested whether activated carbon (AC), a well-known absorbent for secondary metabolites, affect arbuscular mycorrhizal (AM) symbioses and competitive ability in an invasive plant. We conducted three experiments (experiments 1-3) with the invasive forb Solidago canadensis and the native Kummerowia striata. Experiment 1 determined whether AC altered soil properties, levels of the main secondary metabolites in the soil, plant growth, and AMF communities associated with S. canadensis and K. striata. Experiment 2 determined whether AC affected colonization of S. canadensis by five AMF, which were added to sterilized soil. Experiment 3 determined the competitive ability of S. canadensis in the presence and absence of AMF and AC. In experiment 1, AC greatly decreased the concentrations of the main secondary metabolites in soil, and the changes in concentrations were closely related with the changes of AMF in S. canadensis roots. In experiment 2, AC inhibited the AMF Glomus versiforme and G. geosporum but promoted G. mosseae and G. diaphanum in the soil and also in S. canadensis roots. In experiment 3, AC reduced S. canadensis competitive ability in the presence but not in the absence of AMF. Our results provided indirect evidence that the secondary metabolites (which can be absorbed by AC) of the invasive plant S. canadensis may promote S. canadensis competitiveness by enhancing its own AMF symbionts.

  11. A fish-feeding laboratory bioassay to assess the antipredatory activity of secondary metabolites from the tissues of marine organisms.

    Science.gov (United States)

    Marty, Micah J; Pawlik, Joseph R

    2015-01-11

    Marine chemical ecology is a young discipline, having emerged from the collaboration of natural products chemists and marine ecologists in the 1980s with the goal of examining the ecological functions of secondary metabolites from the tissues of marine organisms. The result has been a progression of protocols that have increasingly refined the ecological relevance of the experimental approach. Here we present the most up-to-date version of a fish-feeding laboratory bioassay that enables investigators to assess the antipredatory activity of secondary metabolites from the tissues of marine organisms. Organic metabolites of all polarities are exhaustively extracted from the tissue of the target organism and reconstituted at natural concentrations in a nutritionally appropriate food matrix. Experimental food pellets are presented to a generalist predator in laboratory feeding assays to assess the antipredatory activity of the extract. The procedure described herein uses the bluehead, Thalassoma bifasciatum, to test the palatability of Caribbean marine invertebrates; however, the design may be readily adapted to other systems. Results obtained using this laboratory assay are an important prelude to field experiments that rely on the feeding responses of a full complement of potential predators. Additionally, this bioassay can be used to direct the isolation of feeding-deterrent metabolites through bioassay-guided fractionation. This feeding bioassay has advanced our understanding of the factors that control the distribution and abundance of marine invertebrates on Caribbean coral reefs and may inform investigations in diverse fields of inquiry, including pharmacology, biotechnology, and evolutionary ecology.

  12. Steady-state kinetics of proguanil and its active metabolite, cycloguanil, in man.

    Science.gov (United States)

    Edstein, M D; Veenendaal, J R; Scott, H V; Rieckmann, K H

    1988-01-01

    The pharmacokinetics of proguanil and its active metabolite, cycloguanil, were determined at steady-state in 6 healthy male volunteers after daily administration of 2 Paludrine tablets (200 mg proguanil hydrochloride). A maximum plasma proguanil concentration of 130.3 +/- 16.0 ng/ml (mean +/- SD) was reached at 3.8 +/- 1.3 h while a maximum cycloguanil concentration of 52.0 +/- 15.2 ng/ml was obtained at 5.3 +/- 1.0 h after dosing. The elimination half-lives of proguanil and cycloguanil were 14.5 +/- 3.0 h and 11.7 +/- 3.1 h, respectively. The plasma clearance of proguanil was 1.43 +/- 0.33 l/h/kg and the apparent volume of distribution was 30.7 +/- 12.3 l/kg. Renal clearance of proguanil (0.33 +/- 0.19 l/h/kg) was about 23% of the plasma clearance and 35.6 +/- 9.6% of the oral dose was recovered as proguanil and cycloguanil.

  13. Applicability of fecal estrogenic metabolites estimation for assessment of reproductive activities in sheep

    International Nuclear Information System (INIS)

    Eid, S.Y.A.

    2011-01-01

    The present study was carried out at the sheep experimental farm belonging to Animal Nutrition Unit, Department of Applied Radiobiology, Nuclear Research Center, Egyptian Atomic Energy Authority. Inshas, Sharkia Governorate.Hormonal radioimmunological assay of serum estradiol (E 2 ), estrone (E 1 ), estrone sulphate (E 1 S) and estrone sulphate (E 1 S) in fecal samples was performed in the laboratories of the Endocrinology Research Unit, Applied Radiobiology Department, Applied Radioisotope Division, Nuclear Research Center, Atomic Energy Authority.It was aimed to point out the ovarian estrogens (E 1 , E 2 ) and estrogen metabolite (E 1 S) in both serum and fecal samples, as indicator for reproductive activity in hybrid ewes (Ossimi x Rahmani x Barki, with equal genetic proportion), during estrus cycle, pregnancy and post-partum periods. A total number of 62 ewes were randomly selected according to reproductive farm records and subjected to the study. Estradiol-17β, Estrone and Estrone sulfate were estimated in blood serum. Estrogen sulfate was estimated in fecal samples, estimations were carried out in the various stages of estrus cycle, pregnancy (every 10 days up to the time of parturition) and Postpartum (every 10 days up to 60 days).Fecal samples were collected 24 hours after blood collection to reflect the level of serum estrogenic hormones levels in blood circulation.

  14. Nifurtimox Activation by Trypanosomal Type I Nitroreductases Generates Cytotoxic Nitrile Metabolites*

    Science.gov (United States)

    Hall, Belinda S.; Bot, Christopher; Wilkinson, Shane R.

    2011-01-01

    The prodrug nifurtimox has been used for more than 40 years to treat Chagas disease and forms part of a recently approved combinational therapy that targets West African trypanosomiasis. Despite this, its mode of action is poorly understood. Detection of reactive oxygen and nitrogen intermediates in nifurtimox-treated extracts led to the proposal that this drug induces oxidative stress in the target cell. Here, we outline an alternative mechanism involving reductive activation by a eukaryotic type I nitroreductase. Several enzymes proposed to metabolize nifurtimox, including prostaglandin F2α synthase and cytochrome P450 reductase, were overexpressed in bloodstream-form Trypanosoma brucei. Only cells with elevated levels of the nitroreductase displayed altered susceptibility to this nitrofuran, implying a key role in drug action. Reduction of nifurtimox by this enzyme was shown to be insensitive to oxygen and yields a product characterized by LC/MS as an unsaturated open-chain nitrile. This metabolite was shown to inhibit both parasite and mammalian cell growth at equivalent concentrations, in marked contrast to the parental prodrug. These experiments indicate that the basis for the selectivity of nifurtimox against T. brucei lies in the expression of a parasite-encoded type I nitroreductase. PMID:21345801

  15. Protocol: An updated integrated methodology for analysis of metabolites and enzyme activities of ethylene biosynthesis

    Directory of Open Access Journals (Sweden)

    Geeraerd Annemie H

    2011-06-01

    Full Text Available Abstract Background The foundations for ethylene research were laid many years ago by researchers such as Lizada, Yang and Hoffman. Nowadays, most of the methods developed by them are still being used. Technological developments since then have led to small but significant improvements, contributing to a more efficient workflow. Despite this, many of these improvements have never been properly documented. Results This article provides an updated, integrated set of protocols suitable for the assembly of a complete picture of ethylene biosynthesis, including the measurement of ethylene itself. The original protocols for the metabolites 1-aminocyclopropane-1-carboxylic acid and 1-(malonylaminocyclopropane-1-carboxylic acid have been updated and downscaled, while protocols to determine in vitro activities of the key enzymes 1-aminocyclopropane-1-carboxylate synthase and 1-aminocyclopropane-1-carboxylate oxidase have been optimised for efficiency, repeatability and accuracy. All the protocols described were optimised for apple fruit, but have been proven to be suitable for the analysis of tomato fruit as well. Conclusions This work collates an integrated set of detailed protocols for the measurement of components of the ethylene biosynthetic pathway, starting from well-established methods. These protocols have been optimised for smaller sample volumes, increased efficiency, repeatability and accuracy. The detailed protocol allows other scientists to rapidly implement these methods in their own laboratories in a consistent and efficient way.

  16. Increased antioxidant activity and polyphenol metabolites in methyl jasmonate treated mung bean (Vigna radiata sprouts

    Directory of Open Access Journals (Sweden)

    Li LI

    Full Text Available Abstract Mung bean sprouts are a popular health food both in China and worldwide. We determined the optimal concentration of exogenous methyl jasmonate (MeJA for the promotion of the sprouting in mung beans (Vigna radiata. The 1,1-diphenyl-2- picrylhydrazyl radical (DPPH scavenging test showed that MeJA application resulted in significantly improved antioxidant capacity in the sprouts 72 h later. Measurement of total polyphenols in MeJA-treated beans from 0 to 168 h, using Folin–Ciocalteu colorimetry, showed that the polyphenols changing was significantly correlated with antioxidant activity. The main polyphenols isovitexin, kaempferol-3-O-rutinoside, daidzein, genistein, isoquercitrin, p-coumaric acid, and caffeic acid were quantified using high-performance liquid chromatography (HPLC/QqQ MS and partial least squares discriminant analysis (PLS-DA. MeJA promoted the production of polyphenols, metabolites, and antioxidants in the sprouts; therefore, its use may allow sprouts to be prepared more quickly or increase their nutritional value.

  17. Ecological Roles and Biological Activities of Specialized Metabolites from the Genus Nicotiana.

    Science.gov (United States)

    Jassbi, Amir Reza; Zare, Somayeh; Asadollahi, Mojtaba; Schuman, Meredith C

    2017-10-11

    Species of Nicotiana grow naturally in different parts of the world and have long been used both medicinally and recreationally by human societies. More recently in our history, Nicotiana tabacum has attracted interest as one of the most economically important industrial crops. Nicotiana species are frequently investigated for their bioactive natural products, and the ecological role of their specialized metabolites in responses to abiotic stress or biotic stress factors like pathogens and herbivores. The interest of tobacco companies in genetic information as well as the success of a few wild tobacco species as experimental model organisms have resulted in growing knowledge about the molecular biology and ecology of these plants and functional studies of the plant's natural products. Although a large number of reviews and books on biologically active natural products already exists, mostly from N. tabacum, we focus our attention on the ecological roles and biological activity of natural products, versus products from cured and processed material, in this Review. The studied compounds include alkaloids, aromatic compounds, flavonoids, volatiles, sesquiterpenoids, diterpenes alcohols, and sugar esters from trichomes of the plants, and recently characterized acyclic hydroxygeranyllinalool diterpene glycosides (HGL-DTGs). In this Review (1800s-2017), we describe the above-mentioned classes of natural products, emphasizing their biological activities and functions as they have been determined either in bioassay-guided purification approaches or in bioassays with plants in which the expression of specific biosynthetic genes has been genetically manipulated. Additionally, a review on the history, taxonomy, ecology, and medicinal application of different Nicotiana species growing around the globe presented in this Review may be of interest for pharmacognosists, natural products, and ecological chemists.

  18. The susceptibility of circulating human influenza viruses to tizoxanide, the active metabolite of nitazoxanide.

    Science.gov (United States)

    Tilmanis, Danielle; van Baalen, Carel; Oh, Ding Yuan; Rossignol, Jean-Francois; Hurt, Aeron C

    2017-11-01

    Nitazoxanide is a thiazolide compound that was originally developed as an anti-parasitic agent, but has recently been repurposed for the treatment of influenza virus infections. Thought to exert its anti-influenza activity via the inhibition of hemagglutinin maturation and intracellular trafficking in infected cells, the effectiveness of nitazoxanide in treating patients with non-complicated influenza is currently being assessed in phase III clinical trials. Here, we describe the susceptibility of 210 seasonal influenza viruses to tizoxanide, the active circulating metabolite of nitazoxanide. An optimised cell culture-based focus reduction assay was used to determine the susceptibility of A(H1N1)pdm09, A(H3N2), and influenza B viruses circulating in the southern hemisphere from the period March 2014 to August 2016. Tizoxanide showed potent in vitro antiviral activity against all influenza viruses tested, including neuraminidase inhibitor-resistant viruses, allowing the establishment of a baseline level of susceptibility for each subtype. Median EC 50 values (±IQR) of 0.48 μM (0.33-0.71), 0.62 μM (0.56-0.75), 0.66 μM (0.62-0.69), and 0.60 μM (0.51-0.67) were obtained for A(H1N1)pdm09, A(H3N2), B(Victoria lineage), and B(Yamagata lineage) influenza viruses respectively. There was no significant difference in the median baseline tizoxanide susceptibility for each influenza subtype tested. This is the first report on the susceptibility of circulating viruses to tizoxanide. The focus reduction assay format described is sensitive, robust, and less laborious than traditional cell based antiviral assays, making it highly suitable for the surveillance of tizoxanide susceptibility in circulating seasonal influenza viruses. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Salicylic acid metabolites and derivatives inhibit CDK activity: Novel insights into aspirin's chemopreventive effects against colorectal cancer

    Science.gov (United States)

    Dachineni, Rakesh; Kumar, D. Ramesh; Callegari, Eduardo; Kesharwani, Siddharth S.; Sankaranarayanan, Ranjini; Seefeldt, Teresa; Tummala, Hemachand; Bhat, G. Jayarama

    2017-01-01

    Aspirin's potential as a drug continues to be evaluated for the prevention of colorectal cancer (CRC). Although multiple targets for aspirin and its metabolite, salicylic acid, have been identified, no unifying mechanism has been proposed to clearly explain its chemopreventive effects. Our goal here was to investigate the ability of salicylic acid metabolites, known to be generated through cytochrome P450 (CYP450) enzymes, and its derivatives as cyclin dependent kinase (CDK) inhibitors to gain new insights into aspirin's chemopreventive actions. Using in vitro kinase assays, for the first time, we demonstrate that salicylic acid metabolites, 2,3-dihydroxy-benzoic acid (2,3-DHBA) and 2,5-dihydroxybenzoic acid (2,5-DHBA), as well as derivatives 2,4-dihydroxybenzoic acid (2,4-DHBA), 2,6-dihydroxybenzoic acid (2,6-DHBA), inhibited CDK1 enzyme activity. 2,3-DHBA and 2,6-DHBA did not inhibit CDK2 and 4; however, both inhibited CDK-6 activity. Interestingly, another derivative, 2,4,6-trihydroxybenzoic acid (2,4,6-THBA) was highly effective in inhibiting CDK1, 2, 4 and 6 activity. Molecular docking studies showed that these compounds potentially interact with CDK1. Immunoblotting experiments showed that aspirin acetylated CDK1, and pre-incubation with salicylic acid and its derivatives prevented aspirin-mediated CDK1 acetylation, which supported the data obtained from molecular docking studies. We suggest that intracellularly generated salicylic acid metabolites through CYP450 enzymes within the colonic epithelial cells, or the salicylic acid metabolites generated by gut microflora may significantly contribute to the preferential chemopreventive effect of aspirin against CRC through inhibition of CDKs. This novel hypothesis and mechanism of action in aspirin's chemopreventive effects opens a new area for future research. In addition, structural modification to salicylic acid derivatives may prove useful in the development of novel CDK inhibitors in cancer prevention and

  20. Nondestructive analysis of the RA fuel burnup, Calculation of the gamma activity ratio of fission products in the fuel - program QU0C1

    International Nuclear Information System (INIS)

    Bulovic, V.F.

    1973-01-01

    The γ radiation of RA reactor fuel element was measured under precisely defined measuring conditions. The spectrum was analysed by spectrometer with semiconductor Ge(Li) detector. The gamma counting rate in the fuel spectrum is defined as a function of fission product activity, gamma energy and yield, fuel thickness and additional absorbers, dimensions of the gamma collimator. Activity ratio of two fission products is defined as a function of counting rate peaks and part of the mentioned quantities. Four options for calculating the activities for fission products are discussed. Three of them are covered by the QU0C1 code written in FORTRAN for the CDC 3600 computer. The code is included in this report [sr

  1. Secondary metabolites from Tetracera potatoria stem bark with anti-mycobacterial activity.

    Science.gov (United States)

    Fomogne-Fodjo, M C Y; Ndinteh, D T; Olivier, D K; Kempgens, P; van Vuuren, S; Krause, R W M

    2017-01-04

    Tetracera potatoria Afzel. Exg. Don (Dilleniaceae) is a medicinal plant used traditionally in Africa for the treatment of tuberculosis related ailments and respiratory infections. The antibacterial activity of the medium polar extracts of T. potatoria leaves and stem bark was recently reported against Mycobacterium smegmatis (MIC 25µg/mL) and M. aurum (65µg/mL), two fast-growing Mycobacterium strains used as model micro-organisms for the more pathogenic strain Mycobacterium tuberculosis (Fomogne-Fodjo et al., 2014). The aim of this study was consequently to isolate the compounds possibly contributing to this activity, and which may therefore be promising precursors to be used for the development of novel anti-TB drugs. T. potatoria medium polar extract [MeOH/DCM (1:1, v/v)] was fractionated sequentially with petroleum ether to which EtOAC and MeOH were gradually added to increase the polarity. The examination of T. potatoria extract and its fractions was guided by bioassays for anti-mycobacterial activity against M. smegmatis (ATCC 23246) and M. aurum (NCTC 10437) using the minimum inhibitory concentration (MIC) method. All the isolated compounds were structurally elucidated using spectroscopic techniques and evaluated for their anti-mycobacterial activity. Two novel secondary metabolites (1, 2) named tetraceranoate and N-hydroxy imidate-tetracerane, together with five known compounds [β-stigmasterol (3), stigmast-5-en-3β-yl acetate (4), betulinic acid (5), betulin (6) and lupeol (7)] were isolated and identified. Tetraceranoate exhibited the best activity against M. smegmatis with a minimum inhibitory concentration (MIC) of 7.8µg/mL, while β-stigmasterol, betulinic acid and betulin showed appreciable anti-mycobacterial activity against both strains (MIC 15µg/mL). Seven compounds were isolated from the medium polar extract [MeOH/DCM (1:1, v/v)] of T. potatoria stem bark. Only tetraceranoate one of the isolated compounds showed antibacterial activity against

  2. Determination of 226Ra and 224Ra in drinking waters by liquid scintillation counting

    International Nuclear Information System (INIS)

    Manjon, G.; Vioque, I.; Moreno, H.; Garcia-Tenorio, R.; Garcia-Leon, M.

    1997-01-01

    A method for the determination of Ra-isotopes in water samples has been developed. Ra is coprecipitated with Ba as sulphate. The precipitate is then dissolved with EDTA and counted with a liquid scintillation system after mixing with a scintillation cocktail. The study of the temporal evolution of the separated activity gives the isotopic composition of the sample, i.e. the 224 Ra and 226 Ra contribution to the total activity. The method has been applied to some Spanish drinking waters. (author)

  3. Transport properties of valsartan, sacubitril and its active metabolite (LBQ657) as determinants of disposition.

    Science.gov (United States)

    Hanna, Imad; Alexander, Natalya; Crouthamel, Matthew H; Davis, John; Natrillo, Adrienne; Tran, Phi; Vapurcuyan, Arpine; Zhu, Bing

    2018-03-01

    1. The potential for drug-drug interactions of LCZ696 (a novel, crystalline complex comprising sacubitril and valsartan) was investigated in vitro. 2. Sacubitril was shown to be a highly permeable P-glycoprotein (P-gp) substrate and was hydrolyzed to the active anionic metabolite LBQ657 by human carboxylesterase 1 (CES1b and 1c). The multidrug resistance-associated protein 2 (MRP2) was shown to be capable of LBQ657 and valsartan transport that contributes to the elimination of either compound. 3. LBQ657 and valsartan were transported by OAT1, OAT3, OATP1B1 and OATP1B3, whereas no OAT- or OATP-mediated sacubitril transport was observed. 4. The contribution of OATP1B3 to valsartan transport (73%) was appreciably higher than that by OATP1B1 (27%), Alternatively, OATP1B1 contribution to the hepatic uptake of LBQ657 (∼70%) was higher than that by OATP1B3 (∼30%). 5. None of the compounds inhibited OCT1/OCT2, MATE1/MATE2-K, P-gp, or BCRP. Sacubitril and LBQ657 inhibited OAT3 but not OAT1, and valsartan inhibited the activity of both OAT1 and OAT3. Sacubitril and valsartan inhibited OATP1B1 and OATP1B3, whereas LBQ657 weakly inhibited OATP1B1 but not OATP1B3. 6. Drug interactions due to the inhibition of transporters are unlikely due to the redundancy of the available transport pathways (LBQ657: OATP1B1/OAT1/3 and valsartan: OATP1B3/OAT1/3) and the low therapeutic concentration of the LCZ696 analytes.

  4. Comparative study of genetic activity of chlorambucil's active metabolite steroidal esters: The role of steroidal skeleton on aneugenic potential

    International Nuclear Information System (INIS)

    Efthimiou, M.; Ouranou, D.; Stephanou, G.; Demopoulos, N.A.; Nikolaropoulos, S.S.; Alevizos, Ph.

    2010-01-01

    p-N,N-bis(2-chloroethyl)aminophenylacetic acid (PHE), a nitrogen mustard analogue and chlorambucil's active metabolite used as chemotherapeutic agent, has been shown that, in addition to its clastogenic activity, induces chromosome delay. In the present study an efford has been made (a) to investigate if the steroidal analogues of PHE (EA-92, EA-97, AK-333, AK-409 and AK-433) exert the same genetic activity as the parent compound, (b) to further analyze the aneugenic activity of nitrogen mustard analogues, (c) to investigate the mechanism by which they exert aneugenic potential and (d) to correlate the genetic activity with chemical structure. For this purpose the Cytokinesis Block Micronucleus (CBMN) assay was conducted in human lymphocytes in vitro and the micronucleus (MN) frequency was determined to investigate their genetic activity. The mechanism of micronucleation was determined in combination with Fluorescence In Situ Hybridization (FISH) using pancentromeric DNA probe. Since one of the mechanisms that chemicals cause aneuploidy is through alterations in the mitotic spindle, we also investigated the effect of the above compounds on the integrity and morphology of the mitotic spindle using double immunofluorescence of β- and γ-tubulin in C 2 C 12 mouse cell line. We found that PHE and its steroidal analogues, EA-92, EA-97, AK-333, AK-409 and AK-433, affect cell proliferation in human lymphocytes and C 2 C 12 mouse cells. All studied compounds are capable of inducing chromosome breakage events, as indicated by the enhanced C - MN frequencies. The less lipophilic compounds are the most genetically active molecules. PHE and only two of the studied analogues, AK-409 and AK-433, the most hydrophilic ones, showed aneugenic potential, by increasing the frequencies of MN containing a whole chromosome. The aneugenic potential of the above referred analogues is associated with amplification of centrosome number, since they caused high multipolar metaphase

  5. Comparison of techniques active and passive in measurement of radon concentration ("2"2"2Ra) in the air

    International Nuclear Information System (INIS)

    Oliveira, Evaldo Paulo de

    2017-01-01

    The purpose of this work was to perform a study comparing radon concentration measurements between two techniques used to measure radon gas in the air: one using LEXAN polycarbonate plastic detectors and the other the continuous monitor in AlphaGUARD passive mode. The concentrations of radon gas within radon emanation chambers were measured using calibrated / traceable sources generating "2"2"2Rn through "2"2"6Ra. In calibration the 'calibration factor' or 'sensitivity' was determined for the LEXAN plastic detector. The calibration work of the dosimeters was carried out at the Radon Laboratory of the Environmental Analysis Division - DIRAD IRD/CNEN and at the Natural Radioactivity Laboratory (LRN) of the Center for the Development of Nuclear Technology (CDTN/CNEN). The 'calibration factor' or 'sensitivity' was found to be 32.34 (traits.cm"-"2)/(kBq.d.m"-"3). This factor was used to determine the radon concentration measured by the LEXAN plastic detectors. Also in the calibration, the efficiencies for LEXAN (94.1% ± 9.7%) and AlphaGUARD (92.5% ± 7.2%) were determined. The statistical analysis used showed good parity in the results of the measurements. It was concluded that the results were satisfactory and will serve as a good reference for studies related to the radon air meters used in this work. (author)

  6. Radiochemical determination and separation or total radium, 226Ra and 224Ra

    International Nuclear Information System (INIS)

    Suarez, J. A.; Gonzalez, J. A.; Pablo, M. A. de

    1987-01-01

    Radiochemical purification and separation of radium has been carried out and the determination of total radium solubilized in aqueous samples has been studied assuming that all the alpha emitters of the sample have their origin in the 226Ra and elements of its desintegration chain. Also, the activities of 22Ra and 226 Ra have been evaluated separately doing a measurement after the chemical separation of the radium and another one 10 days after. (Author) 9 refs

  7. Ba(Ra)SO4 species flotation for decontamination of Ra(II) residual solution

    International Nuclear Information System (INIS)

    Stoica, Ligia; Catuneanu, Rodica; Filip, Gheorghe

    1993-01-01

    The paper presents the results of the research performed on Ra(II) separation from complex composition solutions in a HCO 3 - /CO 3 2- buffer system by Ba(Ra)SO 4 precipitation followed by flotation. The collector selection was done by electrokinetic potential determinations. The optimum concentrations of precipitation-flocculation reagents were established on the basis of the experimental data obtained for synthetic solutions having the same Ra(II) activity, namely 20 pCi/l. (authors)

  8. Activation of dormant secondary metabolite production by introducing neomycin resistance into the deep-sea fungus, Aspergillus versicolor ZBY-3.

    Science.gov (United States)

    Dong, Yuan; Cui, Cheng-Bin; Li, Chang-Wei; Hua, Wei; Wu, Chang-Jing; Zhu, Tian-Jiao; Gu, Qian-Qun

    2014-07-29

    A new ultrasound-mediated approach has been developed to introduce neomycin-resistance to activate silent pathways for secondary metabolite production in a bio-inactive, deep-sea fungus, Aspergillus versicolor ZBY-3. Upon treatment of the ZBY-3 spores with a high concentration of neomycin by proper ultrasound irradiation, a total of 30 mutants were obtained by single colony isolation. The acquired resistance of the mutants to neomycin was confirmed by a resistance test. In contrast to the ZBY-3 strain, the EtOAc extracts of 22 of the 30 mutants inhibited the human cancer K562 cells, indicating that these mutants acquired a capability to produce antitumor metabolites. HPLC-photodiode array detector (PDAD)-UV and HPLC-electron spray ionization (ESI)-MS analyses of the EtOAc extracts of seven bioactive mutants and the ZBY-3 strain indicated that diverse secondary metabolites have been newly produced in the mutant extracts in contrast to the ZBY-3 extract. The followed isolation and characterization demonstrated that six metabolites, cyclo(D-Pro-D-Phe) (1), cyclo(D-Tyr-D-Pro) (2), phenethyl 5-oxo-L-prolinate (3), cyclo(L-Ile-L-Pro) (4), cyclo(L-Leu-L-Pro) (5) and 3β,5α,9α-trihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (6), were newly produced by the mutant u2n2h3-3 compared to the parent ZBY-3 strain. Compound 3 was a new compound; 2 was isolated from a natural source for the first time, and all of these compounds were also not yet found in the metabolites of other A. versicolor strains. Compounds 1-6 inhibited the K562 cells, with inhibition rates of 54.6% (1), 72.9% (2), 23.5% (3), 29.6% (4), 30.9% (5) and 51.1% (6) at 100 μg/mL, and inhibited also other human cancer HL-60, BGC-823 and HeLa cells, to some extent. The present study demonstrated the effectiveness of the ultrasound-mediated approach to activate silent metabolite production in fungi by introducing acquired resistance to aminoglycosides and its potential for discovering new compounds from silent fungal

  9. Vertical Profiles Of 226Ra, 232Th And 40K Activities In Rocks From The Irati Formation Of The Paraná Sedimentary Basin, Southern Brazil

    Science.gov (United States)

    Ferreira, Ademar de O.; Bastos, Rodrigo O.; Appoloni, Carlos R.

    2008-08-01

    Naturally occurring radioisotopes are present in different concentrations in sedimentary rocks, reflecting the origin of the sediments, the depositional environment, and more recent events such as weathering and erosion. Using a high-resolution γ-ray spectrometry methodology, sedimentary rocks were measured to assess the concentration activities of the natural radioisotopes. The surveyed rocks are from the Irati formation in the Paraná sedimentary basin, which are exposed by an abandoned, open-pit limestone mine, in the city of Sapopema, southern Brazil. The exposed vertical profile is 5 m, and its stratigraphy is represented by an alternation of limestone and bituminous shale (layers being a few decimeters thick), and some millimeter rhythm layers with limestone and bituminous shale laminas. Eleven samples were collected along this profile, each of them dried in the open air during 48 hours, sieved through 4 mm mesh and sealed in cylindrical recipients. Measurements were accomplished using a 66% relative efficiency HPGE detector connected to a standard gamma ray spectrometry electronic chain. The detector efficiency in the range of 60 to 1800 keV was carried out with the certified IAEA-385 sediment sample. The Lower Limit of Detection (LLD) to the system is 2.40 Bqṡkg-1 for 226Ra, 1.84 Bqṡkg-1 for 232Th and 4.20 Bqṡkg-1 for 40K. Activity concentrations were determined for 226Ra (from 16.22 to 151.55 Bqṡkg-1), 232Th (from 2.93 to 56.12 Bqṡkg-1) and 40K (from 38.45 to 644.63 Bqṡkg-1). The layers enriched with organic matter presented the higher values of activity. The measured concentrations of the natural radioisotopes were lower for limestone samples (average values and respective deviations were 22.81±0.22 Bqṡkg-1 for 226Ra, 4.21±0.07 Bqṡkg-1 for 232Th, and 50.11±0.82 Bqṡkg-1 for 40K). Higher concentrations were measured for the bituminous shale samples (average values and respective deviations were 108.10±12.17 Bqṡkg-1 for 226Ra, 43.69

  10. Vertical Profiles Of 226Ra, 232Th And 40K Activities In Rocks From The Irati Formation Of The Parana Sedimentary Basin, Southern Brazil

    International Nuclear Information System (INIS)

    Ferreira, Ademar de O.; Bastos, Rodrigo O.; Appoloni, Carlos R.

    2008-01-01

    Naturally occurring radioisotopes are present in different concentrations in sedimentary rocks, reflecting the origin of the sediments, the depositional environment, and more recent events such as weathering and erosion. Using a high-resolution γ-ray spectrometry methodology, sedimentary rocks were measured to assess the concentration activities of the natural radioisotopes. The surveyed rocks are from the Irati formation in the Parana sedimentary basin, which are exposed by an abandoned, open-pit limestone mine, in the city of Sapopema, southern Brazil. The exposed vertical profile is 5 m, and its stratigraphy is represented by an alternation of limestone and bituminous shale (layers being a few decimeters thick), and some millimeter rhythm layers with limestone and bituminous shale laminas. Eleven samples were collected along this profile, each of them dried in the open air during 48 hours, sieved through 4 mm mesh and sealed in cylindrical recipients. Measurements were accomplished using a 66% relative efficiency HPGE detector connected to a standard gamma ray spectrometry electronic chain. The detector efficiency in the range of 60 to 1800 keV was carried out with the certified IAEA-385 sediment sample. The Lower Limit of Detection (LLD) to the system is 2.40 Bq·kg -1 for 226 Ra, 1.84 Bq·kg -1 for 232 Th and 4.20 Bq·kg -1 for 40 K. Activity concentrations were determined for 226 Ra (from 16.22 to 151.55 Bq·kg -1 ), 232 Th (from 2.93 to 56.12 Bq·kg -1 ) and 40 K (from 38.45 to 644.63 Bq·kg -1 ). The layers enriched with organic matter presented the higher values of activity. The measured concentrations of the natural radioisotopes were lower for limestone samples (average values and respective deviations were 22.81±0.22 Bq·kg -1 for 226 Ra, 4.21±0.07 Bq·kg -1 for 232 Th, and 50.11±0.82 Bq·kg -1 for 40 K). Higher concentrations were measured for the bituminous shale samples (average values and respective deviations were 108.10±12.17 Bq·kg -1 for

  11. Influence of Different Drying Treatments and Extraction Solvents on the Metabolite Profile and Nitric Oxide Inhibitory Activity of Ajwa Dates.

    Science.gov (United States)

    Abdul-Hamid, Nur Ashikin; Abas, Faridah; Ismail, Intan Safinar; Shaari, Khozirah; Lajis, Nordin H

    2015-11-01

    This study aimed to examine the variation in the metabolite profiles and nitric oxide (NO) inhibitory activity of Ajwa dates that were subjected to 2 drying treatments and different extraction solvents. (1)H NMR coupled with multivariate data analysis was employed. A Griess assay was used to determine the inhibition of the production of NO in RAW 264.7 cells treated with LPS and interferon-γ. The oven dried (OD) samples demonstrated the absence of asparagine and ascorbic acid as compared to the freeze dried (FD) dates. The principal component analysis showed distinct clusters between the OD and FD dates by the second principal component. In respect of extraction solvents, chloroform extracts can be distinguished by the absence of arginine, glycine and asparagine compared to the methanol and 50% methanol extracts. The chloroform extracts can be clearly distinguished from the methanol and 50% methanol extracts by first principal component. Meanwhile, the loading score plot of partial least squares analysis suggested that beta glucose, alpha glucose, choline, ascorbic acid and glycine were among the metabolites that were contributing to higher biological activity displayed by FD and methanol extracts of Ajwa. The results highlight an alternative method of metabolomics approach for determination of the metabolites that contribute to NO inhibitory activity. The association between metabolite profiles and nitric oxide (NO) inhibitory activity of the various extracts of Ajwa dates was evaluated by utilizing partial least squares (PLS) model. The validated PLS model can be employed to predict the NO inhibitory activity of new samples of date fruits based on their NMR spectra which was important for assessing fruit quality. The information gained might be used as guidance for quality control, nutritional values and as a basis for the preparation of any food supplements for human health that employs date palm fruit as the raw material. © 2015 Institute of Food

  12. Combined Mass Spectrometry-Based Metabolite Profiling of Different Pigmented Rice (Oryza sativa L. Seeds and Correlation with Antioxidant Activities

    Directory of Open Access Journals (Sweden)

    Ga Ryun Kim

    2014-09-01

    Full Text Available Nine varieties of pigmented rice (Oryza sativa L. seeds that were black, red, or white were used to perform metabolite profiling by using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS and gas chromatography (GC TOF-MS, to measure antioxidant activities. Clear grouping patterns determined by the color of the rice seeds were identified in principle component analysis (PCA derived from UPLC-Q-TOF-MS. Cyanidin-3-glucoside, peonidin-3-glucoside, proanthocyanidin dimer, proanthocyanidin trimer, apigenin-6-C-glugosyl-8-C-arabiboside, tricin-O-rhamnoside-O-hexoside, and lipids were identified as significantly different secondary metabolites. In PCA score plots derived from GC-TOF-MS, Jakwangdo (JKD and Ilpoom (IP species were discriminated from the other rice seeds by PC1 and PC2. Valine, phenylalanine, adenosine, pyruvate, nicotinic acid, succinic acid, maleic acid, malonic acid, gluconic acid, xylose, fructose, glucose, maltose, and myo-inositol were significantly different primary metabolites in JKD species, while GABA, asparagine, xylitol, and sucrose were significantly distributed in IP species. Analysis of antioxidant activities revealed that black and red rice seeds had higher activity than white rice seeds. Cyanidin-3-glucoside, peonidin-3-glucoside, proanthocyanidin dimers, proanthocyanidin trimers, and catechin were highly correlated with antioxidant activities, and were more plentiful in black and red rice seeds. These results are expected to provide valuable information that could help improve and develop rice-breeding techniques.

  13. Trichloroethylene and Its Oxidative Metabolites Enhance the Activated State and Th1 Cytokine Gene Expression in Jurkat Cells.

    Science.gov (United States)

    Pan, Yao; Wei, Xuetao; Hao, Weidong

    2015-08-28

    Trichloroethylene (TCE) is an occupational and ubiquitous environmental contaminant, and TCE exposure will increase the risk of autoimmune diseases and allergic diseases. T cells play an important role in the pathogenesis of TCE-related immune disorders, but the effect of TCE and its oxidative metabolites, trichloroacetic acid (TCA) and dichloroacetic acid (DCA), on the activation of human T cells is still unknown. In this study, Jurkat cells were pre-treated with TCE, TCA and DCA overnight and then stimulated with phorbol 12-myristate 13-acetate and ionomycin for another 4, 8 and 24 hours. IL-2 secretion was detected by ELISA; the expressions of CD25 and CD69 were tested by flow cytometry; and IFN-γ and IL-2 mRNA expression levels were investigated by real-time PCR. The results showed that TCE and its oxidative metabolites, TCA and DCA, significantly enhanced IL-2 releasing and the expression of T cell activation markers, CD25 and CD69. Consistent with this result, these compounds markedly up-regulated the expression levels of IFN-γ and IL-2 mRNA. Collectively, these findings suggest that TCE and its metabolites, TCA and DCA, might enhance the activation of T cells and disrupt various activities of peripheral T cells.

  14. Trichloroethylene and Its Oxidative Metabolites Enhance the Activated State and Th1 Cytokine Gene Expression in Jurkat Cells

    Directory of Open Access Journals (Sweden)

    Yao Pan

    2015-08-01

    Full Text Available Trichloroethylene (TCE is an occupational and ubiquitous environmental contaminant, and TCE exposure will increase the risk of autoimmune diseases and allergic diseases. T cells play an important role in the pathogenesis of TCE-related immune disorders, but the effect of TCE and its oxidative metabolites, trichloroacetic acid (TCA and dichloroacetic acid (DCA, on the activation of human T cells is still unknown. In this study, Jurkat cells were pre-treated with TCE, TCA and DCA overnight and then stimulated with phorbol 12-myristate 13-acetate and ionomycin for another 4, 8 and 24 hours. IL-2 secretion was detected by ELISA; the expressions of CD25 and CD69 were tested by flow cytometry; and IFN-γ and IL-2 mRNA expression levels were investigated by real-time PCR. The results showed that TCE and its oxidative metabolites, TCA and DCA, significantly enhanced IL-2 releasing and the expression of T cell activation markers, CD25 and CD69. Consistent with this result, these compounds markedly up-regulated the expression levels of IFN-γ and IL-2 mRNA. Collectively, these findings suggest that TCE and its metabolites, TCA and DCA, might enhance the activation of T cells and disrupt various activities of peripheral T cells.

  15. Activities of the Service for maintenance of the RA reactor electronic equipment in 1979 - Report - Annex IV; Prilog IV Rad sluzbe za odrzavanje elektronske opreme reaktora RA u 1979. godini - Izvestaj -

    Energy Technology Data Exchange (ETDEWEB)

    Milosevic, M [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

    1979-12-15

    Within the organizational structure of the RA reactor staff, the Service for instrumentation maintenance has the following tasks: maintenance of the existing electronic equipment; participating in experiments planning and preparation of electronic equipment; purchasing new equipment, spare parts and components; construction of new equipment for internal needs; implementation of new equipment. Basic instrumentation of the reactor facility includes: control and protection system, and dosimetry system. [Serbo-Croat] U okviru organizacione seme OOUR nuklearni reaktor RA sluzba za odrzavanje instrumentacije postrojenja ima sledece zadatke: odrzavanje postojece elektronske opreme; ucesce u planiranju eksperimenata i priprema elektronske opreme; nabavka nove opreme, rezervnih delova i komponenti; rad na izradi elektronske opreme i uredjaja za sopstvene potrebe i izrada projekata u domenu reaktorske opreme i ucesce u ugradnji nove opreme. Osnovna instrumentacija postrojenja obuhvata: sistem za upravljanje i zastitu, sistem za tehnolosku kontrolu i sistem za dozimetrijsku kontrolu.

  16. Influence of mineral salts upon activity of Trichoderma harzianum non-volatile metabolites on Armillaria spp. rhizomorphs

    Directory of Open Access Journals (Sweden)

    Krystyna Przybył

    2011-01-01

    Full Text Available Effect of non-volatile metabolites of Trichoderma harzianum together with certain salts containing Mg++, Fe+++, Mn++, Cu++, Al+++, Ca++, K++, Na+, PO4--- and SO3--- on the production and length of rhizomorphs of Armillaria borealis, A. gallica and A. ostoyae was studied. In pure medium, T. harzianum exhibited stimulating effect on rhizomorphs of A. borealis (both number and length and A. ostoyae (only initiation. Cu++ salt totaly inhibited the initiation of rhizomorphs of Armillaria borealis, A. gallica and A. ostoyae. Effect of other compounds on the activity of T. harzianum depended on Armillaria species. The majority of chemical compounds tested supressed the activity of non-volatile metabolites of T. harzianum. Evident stimulating effect was observed under influence of sulphate salts consisting Al++ and Fe+++ on the rhizomorph number of A. borealis and A. gallica, respectively.

  17. RA Research reactor, Annual report 1988; Istrazivacki nuklearni reaktor RA - Izvestaj za 1988. godinu

    Energy Technology Data Exchange (ETDEWEB)

    Sotic, O [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

    1988-12-15

    Annual report concerning the project 'RA research nuclear reactor' for 1989, financed by the Serbian ministry of science is divided into two parts. First part is concerned with RA reactor operation and maintenance, which is the task of the Division for reactor engineering of the Institute for multidisciplinary studies and RA reactor engineering. Second part deals with radiation protection activities at the RA reactor which is the responsibility of the Institute for radiation protection. Scientific council of the Institute for multidisciplinary studies and RA reactor engineering has stated that this report describes adequately the activity and tasks fulfilled at the RA reactor in 1989. The scope and the quality of the work done were considered successful both concerning the maintenance and reconstruction, as well as radiation protection activities. [Serbo-Croat] Godisnji izvestaj po projektu 'Istrazivacki nuklearni reaktor RA' za 1989. godinu, koji finansira republicka zajednica za nauku SR Srbije po ugovoru br. 3705/1 sastoji se iz dva dela. Prvi deo obuhvata pogon i odrzavanje nuklearnog reaktora RA, sto predstavlja obavezu Odeljenja za reaktorski inzenjering u sastavu OOUR Instituta za multidisciplinarna istrazivanja i inzenjering RA. Drugi deo obuhvata poslove zastite od zracenja na reaktoru RA, sto predstavlja obavezu OOUR Instituta za zastitu od zracenja 'Zastita'. Naucno vece Instituta za multidisciplinarna istrazivanja i inzenjering RA ocenilo je da sadrzina ovog izvestaja odgovara izvrsenim poslovima na reaktoru RA u 1989. godini. Pozitivno se ocenjuje obim i kvalitet izvrsenih radova kako u pogledu odrzavanja i rekonstrukcije reaktora, tako i u pogledu poslova zastite od zracenja izvrsenih kod njega.

  18. Research nuclear reactor RA - Annual Report 1989; Istrazivacki nuklearni reaktor RA - Izvestaj za 1989. godinu

    Energy Technology Data Exchange (ETDEWEB)

    Sotic, O [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

    1989-12-15

    Annual report concerning the project 'RA research nuclear reactor' for 1989, financed by the Serbian ministry of science is divided into two parts. First part is concerned with RA reactor operation and maintenance, which is the task of the Division for reactor engineering of the Institute for multidisciplinary studies and RA reactor engineering. Second part deals with radiation protection activities at the RA reactor which is the responsibility of the Institute for radiation protection. Scientific council of the Institute for multidisciplinary studies and RA reactor engineering has stated that this report describes adequately the activity and tasks fulfilled at the RA reactor in 1989. The scope and the quality of the work done were considered successful both concerning the maintenance and reconstruction, as well as radiation protection activities. [Serbo-Croat] Godisnji izvestaj po projektu 'Istrazivacki nuklearni reaktor RA' za 1989. godinu, koji finansira republicka zajednica za nauku SR Srbije po ugovoru br. 3705/1 sastoji se iz dva dela. Prvi deo obuhvata pogon i odrzavanje nuklearnog reaktora RA, sto predstavlja obavezu Odeljenja za reaktorski inzenjering u sastavu OOUR Instituta za multidisciplinarna istrazivanja i inzenjering RA. Drugi deo obuhvata poslove zastite od zracenja na reaktoru RA, sto predstavlja obavezu OOUR Instituta za zastitu od zracenja 'Zastita'. Naucno vece Instituta za multidisciplinarna istrazivanja i inzenjering RA ocenilo je da sadrzina ovog izvestaja odgovara izvrsenim poslovima na reaktoru RA u 1989. godini. Pozitivno se ocenjuje obim i kvalitet izvrsenih radova kako u pogledu odrzavanja i rekonstrukcije reaktora, tako i u pogledu poslova zastite od zracenja izvrsenih kod njega.

  19. Not flavone-8-acetic acid (FAA) but its murine metabolite 6-OH-FAA exhibits remarkable antivascular activities in vitro.

    Science.gov (United States)

    Pham, Minh Hien; Dauzonne, Daniel; Chabot, Guy G

    2016-06-01

    Flavone-8-acetic acid (FAA) has been proved to be a potent vascular-disrupting agent in mice. Unfortunately, FAA did not produce any anticancer activity in clinical trials. Previously, we had reported that FAA is metabolized by mouse microsomes into six metabolites, whereas it was poorly metabolized by human microsomes, with fewer metabolites formed in lesser amounts. Especially, 6-OH-FAA was not formed by human microsomes. In this work, two major available metabolites, 4'-OH-FAA and 6-OH-FAA, were tested and compared with the parent compound FAA for their potential antivascular activities in vitro. The ability of the products to induce morphological changes, disrupt preformed capillaries of EA.hy926 endothelial cells and inhibit tubulin polymerization in vitro was assessed. The action mechanism was determined using the RhoA and Rac1 inhibitors. At 25 µg/ml, 6-OH-FAA induced morphological changes and membrane blebbing, whereas 300 µg/ml of FAA and 4'-OH-FAA slightly changed the morphology without inducing membrane blebbing. At 300 µg/ml, 6-OH-FAA produced morphological changes that were 2.1-6.9-fold greater than that produced by FAA and 4'-OH-FAA, an effect that was consistent with its much greater inhibitory effect on tubulin polymerization compared with FAA and 4'-OH-FAA. 6-OH-FAA significantly disrupted the EA.hy926 cell capillaries. 6-OH-FAA activities were prevented in EA.hy926 cells pretreated with RhoA, but not Rac1, inhibitor. In this short communication we report for the first time that, in vitro, 6-OH-FAA, a mouse-specific FAA metabolite, exhibits significantly stronger antivascular activities compared with FAA and 4'-OH-FAA, which are mediated through the RhoA kinase pathway.

  20. Baicalin and its metabolites suppresses gluconeogenesis through activation of AMPK or AKT in insulin resistant HepG-2 cells.

    Science.gov (United States)

    Wang, Tao; Jiang, Hongmei; Cao, Shijie; Chen, Qian; Cui, Mingyuan; Wang, Zhijie; Li, Dandan; Zhou, Jing; Wang, Tao; Qiu, Feng; Kang, Ning

    2017-12-01

    Scutellaria baicalensis Georgi (S. baicalensis), as a traditional Chinese herbal medicine, is an important component of several famous Chinese medicinal formulas for treating patients with diabetes mellitus. Baicalin (BG), a main bioactive component of S. baicalensis, has been reported to have antidiabetic effects. However, pharmacokinetic studies have indicated that BG has poor oral bioavailability. Therefore, it is hard to explain the pharmacological effects of BG in vivo. Interestingly, several reports show that BG is extensively metabolized in rats and humans. Therefore, we speculate that the BG metabolites might be responsible for the pharmacological effects. In this study, BG and its three metabolites (M1-M3) were examined their effects on glucose consumption in insulin resistant HepG-2 cells with a commercial glucose assay kit. Real-time PCR and western blot assay were used to confirm genes and proteins of interest, respectively. The results demonstrate that BG and its metabolites (except for M3) enhanced the glucose consumption which might be associated with inhibiting the expression of the key gluconeogenic genes, including glucose-6-phosphatase (G6Pase), phosphoenolypyruvate carboxykinase (PEPCK) and glucose transporter 2 (GLUT2). Further study found that BG and M1 could suppress hepatic gluconeogenesis via activation of the AMPK pathway, while M2 could suppress hepatic gluconeogenesis via activation of the PI3K/AKT signaling pathway. Taken together, our findings suggest that both BG and its metabolites have antihyperglycemic activities, and might be the active forms of oral doses of BG in vivo. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. Fisetin disposition and metabolism in mice: Identification of geraldol as an active metabolite. : Fisetin disposition and metabolism in mice

    OpenAIRE

    Touil, Yasmine,; Auzeil, Nicolas; Boulinguez, François; Saighi, Hanane; Regazzetti, Anne; Scherman, Daniel; Chabot, Guy,

    2011-01-01

    International audience; Although the natural flavonoid fisetin (3,3',4',7-tetrahydroxyflavone) has been recently identified as an anticancer agent with antiangiogenic properties in mice, its in vivo pharmacokinetics and metabolism are presently not characterized. Our purpose was to determine the pharmacokinetics and metabolism of fisetin in mice and determine the biological activity of a detected fisetin metabolite. After fisetin administration of an efficacious dose of 223 mg/kg i.p. in mice...

  2. Determination of sup 226 Ra and sup 228 Ra in gypsum

    Energy Technology Data Exchange (ETDEWEB)

    Godoy, J M [Instituto de Radioprotecao e Dosimetria, Rio de Janeiro, RJ (Brazil)

    1989-01-01

    The content of {sup 226}Ra and {sup 228}Ra in different samples of phosphogypsum and three samples of gypsite were determined by gamma spectroscopy. For {sup 226}Ra the 295, 352 and 609 KeV lines and for {sup 228}Ra the 911 and 969 KeV lines were used. The specific activities values ranged from 0.36 to 22.8 pCi/g for {sup 226}Ra and 0.90 to 10.3 pCi/g for {sup 228}Ra. The contribution of a sypsum roof-covering to the {sup 222}Rn concentration in a room was estimated, based on the highest value reported. (author).

  3. RA Construction KC, LLC Information Sheet

    Science.gov (United States)

    RA Construction KC, LLC (the Company) is located in Gladstone, Missouri. The settlement involves renovation activities conducted at a property constructed prior to 1978, located in Kansas City, Missouri.

  4. Radioimmunoassay of pharmacologically active compounds: applications to nicotine and its metabolites

    International Nuclear Information System (INIS)

    Langone, J.J.; Vunakis, H. van

    1979-01-01

    Since nicotine is the major tobacco alkaloid, its role in cardiovascular disease, cancer and other physiological effects of cigarette smoking has been the subject of intensive investigation for many years. As part of this investigation into the biochemical and physiological effects of nicotine, the authors developed sensitive and specific radioimmunoassays for the parent alkaloid, a major metabolite cotinine, and for γ-(3-pyridyl)-γ-oxo-N-methylbutyramide (oxoamide). The oxoamide is a minor metabolite derived from cotinine. The authors describe the development of these RIA's and demonstrate their use in determining levels of these compounds in physiological fluids of smokers and in studying metabolic processes in vitro. (Auth.)

  5. The potentially beneficial central nervous system activity profile of ivacaftor and its metabolites

    Directory of Open Access Journals (Sweden)

    Elena K. Schneider

    2018-03-01

    Full Text Available Ivacaftor–lumacaftor and ivacaftor are two new breakthrough cystic fibrosis transmembrane conductance modulators. The interactions of ivacaftor and its two metabolites hydroxymethylivacaftor (iva-M1 and ivacaftorcarboxylate (iva-M6 with neurotransmitter receptors were investigated in radioligand binding assays. Ivacaftor displayed significant affinity to the 5-hydroxytryptamine (5-HT; serotonin 5-HT2C receptor (pKi=6.06±0.03, β3-adrenergic receptor (pKi=5.71±0.07, δ-opioid receptor (pKi=5.59±0.06 and the dopamine transporter (pKi=5.50±0.20; iva-M1 displayed significant affinity to the 5-HT2C receptor (pKi=5.81±0.04 and the muscarinic M3 receptor (pKi=5.70±0.10; iva-M6 displayed significant affinity to the 5-HT2A receptor (pKi=7.33±0.05. The in vivo central nervous system activity of ivacaftor (40 mg·kg−1 intraperitoneally for 21 days was assessed in a chronic mouse model of depression. In the forced swim test, the ivacaftor-treated group displayed decreased immobility (52.8±7.6 s, similarly to fluoxetine (33.8±11.0 s, and increased climbing/swimming activity (181.5±9.2 s. In the open field test, ivacaftor produced higher locomotor activity than the fluoxetine group, measured both as mean number of paw touches (ivacaftor 81.1±9.6 versus fluoxetine 57.9±9.5 and total distance travelled (ivacaftor 120.6±16.8 cm versus fluoxetine 84.5±16.0 cm in 600 s. Treatment of 23 cystic fibrosis patients with ivacaftor–lumacaftor resulted in significant improvements in quality of life (including anxiety in all five domains of the AweScoreCF questionnaire (p=0.092–0.096. Our findings suggest ivacaftor displays potential clinical anxiolytic and stimulating properties, and may have beneficial effects on mood.

  6. Production of sealed sup 6 sup 0 Co and sup 1 sup 9 sup 2 Ir sources of high specific activity in the nuclear reactor RA

    International Nuclear Information System (INIS)

    Dobrijevic, R.; Vucina, J.

    1998-01-01

    Given is a review on the development of the production of 60 Co and 192 Ir performed in the Vinca Institute in the nuclear reactor RA. The experience gained showed that this reactor was suitable for obtaining of these and some other radionuclides. One possibility of its re-start is that the performances of the reactor remain the same (power 6.5 MW, max.neutron flux up to 6x10 13 n.cm -2 s -1 ). By applying new techniques of target preparation, 60 Co for sterilization units of specific activity 1.11 TBq/g could be produced. Maximal activity of sup 1 sup 9 sup 2 Ir would be about 1.48 TBq what is satisfactory for the sources for gamma radiography. The increase of the flux to 10 14 n.cm -2 s -1 would enable the production of 60 Co of specific activities about 3.335 TBq/g. This is satisfactory for the sources for the radiation therapy of activities up to 111 TBq and for gamma radiography of activities about 0.37 TBq. In the case of 192 Ir the sources for the radiation therapy of activities about 0.37 TBq could be obtained. Maximal achievable activities of 192 Ir would be about 3.7 TBq. (author)

  7. 226Ra and 228Ra in ground water of the Cambrian-Ordovician Aquifer System in northern Illinois

    International Nuclear Information System (INIS)

    Gilkeson, R.H.; Holtzman, R.B.

    1982-01-01

    Over a large region of Illinois, ground water of the Cambrian-Ordovician Aquifer System exceeds the US EPA drinking water standard of 5 pCi/L for the combined concentration of 226 Ra and 228 Ra. 226 Ra concentrations range from 226 Ra is the geochemistry of uranium in the ground-water flow system, while the 228 Ra activity in ground water which ranges from 232 Th-bearing minerals in the aquifer strata. The comparison of recent analyses to historical data gathered over the last 20 years indicates that, with few exceptions, 226 Ra and 228 Ra activities in ground water have remained constant. The combined concentrations of the two nuclides in ground water of the aquifer system ranged from 226 Ra concentrations were high (greater than or equal to 10 pCi/L), those of 228 Ra were low (less than or equal to 2 pCi/L), but, with few exceptions, in regions where 228 Ra concentrations were high, those of 226 Ra were also high. The range of values raises questions concerning the validity of the US EPA regulation which requires analysis for 228 Ra only when the concentration of 226 Ra exceeds 3.0 pCi/L

  8. Antifungal activity of secondary plant metabolites from potatoes (Solanum tuberosum L.): Glycoalkaloids and phenolic acids show synergistic effects.

    Science.gov (United States)

    Sánchez-Maldonado, A F; Schieber, A; Gänzle, M G

    2016-04-01

    To study the antifungal effects of the potato secondary metabolites α-solanine, α-chaconine, solanidine and caffeic acid, alone or combined. Resistance to glycoalkaloids varied among the fungal species tested, as derived from minimum inhibitory concentrations assays. Synergistic antifungal activity between glycoalkaloids and phenolic compounds was found. Changes in the fluidity of fungal membranes caused by potato secondary plant metabolites were determined by calculation of the generalized polarization values. The results partially explained the synergistic effect between caffeic acid and α-chaconine and supported findings on membrane disruption mechanisms from previous studies on artificial membranes. LC/MS analysis was used to determine variability and relative amounts of sterols in the different fungal species. Results suggested that the sterol pattern of fungi is related to their resistance to potato glycoalkaloids and to their taxonomy. Fungal resistance to α-chaconine and possibly other glycoalkaloids is species dependent. α-Chaconine and caffeic acid show synergistic antifungal activity. The taxonomic classification and the sterol pattern play a role in fungal resistance to glycoalkaloids. Results improve the understanding of the antifungal mode of action of potato secondary metabolites, which is essential for their potential utilization as antifungal agents in nonfood systems. © 2016 The Society for Applied Microbiology.

  9. Integrated circuit-based electrochemical sensor for spatially resolved detection of redox-active metabolites in biofilms.

    Science.gov (United States)

    Bellin, Daniel L; Sakhtah, Hassan; Rosenstein, Jacob K; Levine, Peter M; Thimot, Jordan; Emmett, Kevin; Dietrich, Lars E P; Shepard, Kenneth L

    2014-01-01

    Despite advances in monitoring spatiotemporal expression patterns of genes and proteins with fluorescent probes, direct detection of metabolites and small molecules remains challenging. A technique for spatially resolved detection of small molecules would benefit the study of redox-active metabolites that are produced by microbial biofilms and can affect their development. Here we present an integrated circuit-based electrochemical sensing platform featuring an array of working electrodes and parallel potentiostat channels. 'Images' over a 3.25 × 0.9 mm(2) area can be captured with a diffusion-limited spatial resolution of 750 μm. We demonstrate that square wave voltammetry can be used to detect, identify and quantify (for concentrations as low as 2.6 μM) four distinct redox-active metabolites called phenazines. We characterize phenazine production in both wild-type and mutant Pseudomonas aeruginosa PA14 colony biofilms, and find correlations with fluorescent reporter imaging of phenazine biosynthetic gene expression.

  10. The selenium metabolite methylselenol regulates the expression of ligands that trigger immune activation through the lymphocyte receptor NKG2D

    DEFF Research Database (Denmark)

    Hagemann-Jensen, Michael Henrik; Uhlenbrock, Franziska Katharina; Kehlet, Stephanie

    2014-01-01

    For decades Selenium (Se) research has been focused on the identification of active metabolites, which are crucial for Se chemoprevention of cancer. In this context, the metabolite methylselenol (CH3SeH) is known for its action to selectively kill transformed cells through mechanisms that include...... ligands. A balanced cell-surface expression of NKG2D ligands is considered as an innate barrier against tumor development. Our work therefore indicates that the application of selenium compounds, which are metabolized to CH3SeH, could improve NKG2D-based immune therapy.......: Increased formation of reactive oxygen species (ROS), induction of DNA damage, triggering of apoptosis and the inhibition of angiogenesis. Here, we revealed that CH3SeH modulates cell surface expression of NKG2D ligands. The expression of NKG2D ligands is induced by stress-associated pathways, which occur...

  11. Plant-Derived Polyphenols in Human Health: Biological Activity, Metabolites and Putative Molecular Targets.

    Science.gov (United States)

    Olivares-Vicente, Marilo; Barrajon-Catalan, Enrique; Herranz-Lopez, Maria; Segura-Carretero, Antonio; Joven, Jorge; Encinar, Jose Antonio; Micol, Vicente

    2018-01-01

    Hibiscus sabdariffa, Lippia citriodora, Rosmarinus officinalis and Olea europaea, are rich in bioactive compounds that represent most of the phenolic compounds' families and have exhibited potential benefits in human health. These plants have been used in folk medicine for their potential therapeutic properties in human chronic diseases. Recent evidence leads to postulate that polyphenols may account for such effects. Nevertheless, the compounds or metabolites that are responsible for reaching the molecular targets are unknown. data based on studies directly using complex extracts on cellular models, without considering metabolic aspects, have limited applicability. In contrast, studies exploring the absorption process, metabolites in the blood circulation and tissues have become essential to identify the intracellular final effectors that are responsible for extracts bioactivity. Once the cellular metabolites are identified using high-resolution mass spectrometry, docking techniques suppose a unique tool for virtually screening a large number of compounds on selected targets in order to elucidate their potential mechanisms. we provide an updated overview of the in vitro and in vivo studies on the toxicity, absorption, permeability, pharmacokinetics and cellular metabolism of bioactive compounds derived from the abovementioned plants to identify the potential compounds that are responsible for the observed health effects. we propose the use of targeted metabolomics followed by in silico studies to virtually screen identified metabolites on selected protein targets, in combination with the use of the candidate metabolites in cellular models, as the methods of choice for elucidating the molecular mechanisms of these compounds. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Active Oxygen Metabolites and Thromboxane in Phorbol Myristate Acetate Toxicity to the Isolated, Perfused Rat Lung.

    Science.gov (United States)

    Carpenter, Laurie Jean

    When administered intravenously or intratracheally to rats, rabbits and sheep, phorbol myristate acetate (PMA) produces changes in lung morphology and function are similar to those seen in humans with the adult respiratory distress syndrome (ARDS). Therefore, it is thought that information about the mechanism of ARDS development can be gained from experiments using PMA-treated animals. Currently, the mechanisms by which PMA causes pneumotoxicity are unknown. Results from other studies in rabbits and in isolated, perfused rabbit lungs suggest that PMA-induced lung injury is mediated by active oxygen species from neutrophils (PMN), whereas studies in sheep and rats suggest that PMN are not required for the toxic response. The role of PMN, active oxygen metabolites and thromboxane (TxA_2) in PMA-induced injury to isolated, perfused rat lungs (IPLs) was examined in this thesis. To determine whether PMN were required for PMA to produce toxicity to the IPL, lungs were perfused for 30 min with buffer containing various concentrations of PMA (in the presence or absence of PMN). When concentrations >=q57 ng/ml were added to medium devoid of added PMN, perfusion pressure and lung weight increased. When a concentration of PMA (14-28 ng/ml) that did not by itself cause lungs to accumulate fluid was added to the perfusion medium containing PMN (1 x 10 ^8), perfusion pressure increased, and lungs accumulated fluid. These results indicate that high concentrations of PMA produce lung injury which is independent of PMN, whereas injury induced by lower concentrations is PMN-dependent. To examine whether active oxygen species were involved in mediating lung injury induced by PMA and PMN, lungs were coperfused with the oxygen radical scavengers SOD and/or catalase. Coperfusion with either or both of these enzymes totally protected lungs against injury caused by PMN and PMA. These results suggest that active oxygen species (the hydroxyl radical in particular), mediate lung injury in

  13. 228Ra in monazite processing

    International Nuclear Information System (INIS)

    Paul, A.C.; Pillai, K.C.

    1979-01-01

    The treatment of monazite, adopted by the Indian Rare Earths plant is based on alkali digestion by caustic soda and acid leaching by hydrochloric acid. The paper deals with the distribution of 228 Ra, the daughter product of 232 Th in the effluents and outlines the treatment procedures adopted to reduce its levels. The activity gets distributed into the soluble and insoluble fractions in the effluent depending on its acidic/alkaline nature. The scheme for further deactivation of the effluent was based on lime treatment. It is observed that more than 95% removal of Ra is achievable by the treatment. The procedures leading to the proposed final treatment and disposal of effluent are schematically represented. Some environmental data are presented to show the impact of effluent releases in river, water and sediments. (B.G.W.)

  14. Radiation protection at reactors RA and RB

    International Nuclear Information System (INIS)

    Ninkovic, M.

    2003-02-01

    Radiation protection activities at the RA and RB reactors are imposed by the existing legal regulations and international recommendations in this field. This annual report contains five parts which cover the following topics: Radiation safety, dosimetry control and technical radiation protection at reactors RA and RB; Handling of radioactive waste, actions and decontamination; Control of the environment (surroundings of RA and RB reactors) and meteorological measurements; Control of internal contamination and internal exposure; Health control od personnel exposed to radiation. Personnel as well as financial data are part of this report

  15. Assessment of 226Ra, 228Ra and 40K contents in the Egyptian bottled natural water

    International Nuclear Information System (INIS)

    El-Afifi, E.M.; Hilal, M.A.; Khalifa, S.M.; Aly, H.F.

    2004-01-01

    The activity concentrations of 2 26Ra, 2 28Ra and 4 0 and k in different brands of the bottled egyptian natural water of different origins obtained from four regions, have been analyzed nondestructively by gamma- ray spectrometry. The study covers nine brands of natural water commonly used mainly for drinking in egypt. The results showed, concentrations up to 184, 156 and 1700 mBq I - 1 for 2 26Ra, 2 28Ra and 4 0K, respectively, in one brand of the natural water from water from Siwa oasis. Whereas, lower activity concentrations of 2 26Ra and 2 28Ra were found in one brand of these natural waters from El sadat region. The activity concentration of 4 0K was found to be in the background range in the brands from El sadat, kafr El arbein and beilbeis regions. The committed effective doses reached 1.9 x 10 - 2 m Sy Y - 1 for ingestion of 2 26Ra and 2 28Ra for one liter per day, respectively, which are lower than the standard permissible limit by the WHO and IAEA. However, it is recommended to moderate drinking of bottled natural water to avoid the accumulation effect of radioactive nuclides especially radium

  16. Characterization of the neutron flow for the implementation of an experimental analysis installation for rapid gamma activation in the Argentine Research Reactor RA-6

    International Nuclear Information System (INIS)

    Henriquez, C.; Gennuso, G.

    2000-01-01

    This is the final work to obtain a Diploma on Specialization in Application of Nuclear Technological Energy, carried out at the Research Reactor RA-6, from March to December 1999. Different work has been realized on the Tangential Tube N of the 500 KW Argentine RA-6 research reactor, in order to add a new technique to the present existing analytical methods. This Prompt Gamma Neutron Activation Analysis technique (PGNAA) requires a beam of collimated thermal neutrons, a lowest possible gamma radiation, and a thermal component of the biggest possible cadmium rate. It also must have a high resolution detection system for the measurement of the gamma radiation emitted after the capture of the neutron produced in the study sample. Continuing with the facility's technical requirements, a collimator was installed inside the N passing tube, in order to concentrate the neutrons coming from the nuclear core and also to compensate possible losses during the path. This collimator is 440mm long and 200 mm in diameter and consists of lead and steel cylinders with different size holes on the inside, so that it can deliver a 50 mm diameter beam of thermal collimated neutrons. Two 100 mm thick bismuth filters are inside the passing tube, to reduce the gamma component inside de beam, coming from the reactor core. This work aims to the characterization of the thermal and epithermal component of the neutron beam in the collimator and at the exit of it , and also to prove experimentally that the collimator achieves the technical specifications for which it was designed and built, specifically by verifying its functioning (degree of convergence of the beam obtained). On the other hand, it is necessary to learn about the PGNAA technique in order to define the technical requirements for its adequate operation. (author)

  17. Activity of the Service for maintenance of mechanical equipment of the RA reactor - Report, Annex II; Prilog II - Rad sluzbe za odrzavanje masinske opreme reaktora RA u 1979. godini - Izvestaj -

    Energy Technology Data Exchange (ETDEWEB)

    Radivojevic, J [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

    1979-12-15

    Service for mechanical components at the RA reactor includes: control and maintenance of utility components, mechanical workshop, hot cells and storage. Control and maintenance of main components covers: reactor core, heavy water system, technical water system, gas system. This service is responsible for the following auxiliary systems: transportation units; spent fuel storage pool; special ventilation system; personal protection appliances; hot cells. Maintenance of the reactor building, ventilation, heating, water supply, sewage, fire protection devices, gas and compressed air systems are included. [Serbo-Croat] Sluzba za masinsku opremu nuklearnog reaktora RA obuhvata: kontrolu i odrzavanje masinske opreme postrojenja, masinsku radionicu, vruce komore i prirucni magacin. Kontrola i odrzavanje osnovnih sistema obuhvata centralno telo reaktora, sistem teske vode, sistem tehnicke vode, gasni sistem. Pomocni sistemi koji spadaju u delatnost ove sluzbe su: transportna oprema, bazen za odlezavanje ozracenog goriva, sistem specijalne ventilacije, licna zastitna sredstva, vruce komore. Odrzavanje zgrade reaktora, ventilacije i grejanja, vodovoda i kanalizacije, opreme za protivpozarnu zastitu, instalacije gasa i komprimovanog vazduha su takode zadatak ove Sluzbe.

  18. Activity of the Service for maintenance of mechanical structures of the RA reactor - Report for 1980, Annex II; Prilog II - Rad sluzbe za odrzavanje masinske opreme reaktora RA - Izvestaj za 1980. god

    Energy Technology Data Exchange (ETDEWEB)

    Radivojevic, J [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

    1980-12-15

    Service for mechanical components at the RA reactor includes: control and maintenance of utility components, mechanical workshop, hot cells and storage. Control and maintenance of main components covers: reactor core, heavy water system, technical water system, gas system. This service is responsible for the following auxiliary systems: transportation units; spent fuel storage pool; special ventilation system; personal protection appliances; hot cells. Maintenance of the reactor building, ventilation, heating, water supply, sewage, fire protection devices, gas and compressed air systems are included. [Serbo-Croat] Sluzba za masinsku opremu nuklearnog reaktora RA obuhvata: kontrolu i odrzavanje masinske opreme postrojenja, masinsku radionicu, vruce komore i prirucni magacin. Kontrola i odrzavanje osnovnih sistema obuhvata centralno telo reaktora, sistem teske vode, sistem tehnicke vode, gasni sistem. Pomocni sistemi koji spadaju u delatnost ove sluzbe su: transportna oprema, bazen za odlezavanje ozracenog goriva, sistem specijalne ventilacije, licna zastitna sredstva, vruce komore. Odrzavanje zgrade reaktora, ventilacije i grejanja, vodovoda i kanalizacije, opreme za protivpozarnu zastitu, instalacije gasa i komprimovanog vazduha su takode zadatak ove Sluzbe.

  19. Concentration in activity of 137 Cs, 40 K, 232 Th, 226 Ra in waste deposits of the benefits of minerals in the State of Zacatecas

    International Nuclear Information System (INIS)

    Leal, B.; Mireles, F.; Quirino, L.; Davila, I.; Ramirez, F.

    2003-01-01

    The necessity to report the changes in the contained radionuclides in the terrestrial crust, or those deposited by the atomic tests around the world, becomes clear when observing the use of material of waste of those mines. With the purpose of quantifying the concentration in activity its were meet a series of waste samples in mines of the municipalities of Zacatecas, Fresnillo, Guadalupe and Veta Grande of the state of Zacatecas, Mexico. The analysis was carried out by gamma spectrometry with a HPGe detector with a resolution of 1.9 keV corresponding to an energy of 1.33 MeV calibrated in efficiency and energy by means of a certified standard multi nuclide in activity with identical geometry to that of the samples. The times of count are of 80000 seconds, with the purpose of to reduce the relative uncertainties and to define well the interest regions. The activity of 226 Ra and 232 Th is obtained through the one 214 Bi and 228 Ac respectively, the concentration was also measured in activity of the one 40 K and the 137 Cs in units of Bq kg -1 . (Author)

  20. Activation of the sigma-1 receptor by haloperidol metabolites facilitates brain-derived neurotrophic factor secretion from human astroglia.

    Science.gov (United States)

    Dalwadi, Dhwanil A; Kim, Seongcheol; Schetz, John A

    2017-05-01

    Glial cells play a critical role in neuronal support which includes the production and release of the neurotrophin brain-derived neurotrophic factor (BDNF). Activation of the sigma-1 receptor (S1R) has been shown to attenuate inflammatory stress-mediated brain injuries, and there is emerging evidence that this may involve a BDNF-dependent mechanism. In this report we studied S1R-mediated BDNF release from human astrocytic glial cells. Astrocytes express the S1R, which mediates BDNF release when stimulated with the prototypical S1R agonists 4-PPBP and (+)-SKF10047. This effect could be antagonized by a selective concentration of the S1R antagonist BD1063. Haloperidol is known to have high affinity interactions with the S1R, yet it was unable to facilitate BDNF release. Remarkably, however, two metabolites of haloperidol, haloperidol I and haloperidol II (reduced haloperidol), were discovered to facilitate BDNF secretion and this effect was antagonized by BD1063. Neither 4-PPBP, nor either of the haloperidol metabolites affected the level of BDNF mRNA as assessed by qPCR. These results demonstrate for the first time that haloperidol metabolites I and II facilitate the secretion of BDNF from astrocytes by acting as functionally selective S1R agonists. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Pharmacologic activity and pharmacokinetics of metabolites of regorafenib in preclinical models

    OpenAIRE

    Zopf, Dieter; Fichtner, Iduna; Bhargava, Ajay; Steinke, Wolfram; Thierauch, Karl?Heinz; Diefenbach, Konstanze; Wilhelm, Scott; Hafner, Frank?Thorsten; Gerisch, Michael

    2016-01-01

    Abstract Regorafenib is an orally administered inhibitor of protein kinases involved in tumor angiogenesis, oncogenesis, and maintenance of the tumor microenvironment. Phase III studies showed that regorafenib has efficacy in patients with advanced gastrointestinal stromal tumors or treatment?refractory metastatic colorectal cancer. In clinical studies, steady?state exposure to the M?2 and M?5 metabolites of regorafenib was similar to that of the parent drug; however, the contribution of thes...

  2. The urinary metabolites of DINCH® have an impact on the activities of the human nuclear receptors ERα, ERβ, AR, PPARα and PPARγ.

    Science.gov (United States)

    Engel, Anika; Buhrke, Thorsten; Kasper, Stefanie; Behr, Anne-Cathrin; Braeuning, Albert; Jessel, Sönke; Seidel, Albrecht; Völkel, Wolfgang; Lampen, Alfonso

    2018-05-01

    DINCH ® (di-isononyl cyclohexane-1,2-dicarboxylate) is a non-phthalate plasticizer that has been developed to replace phthalate plasticizers such as DEHP (di-2-ethylhexyl phthalate) or DINP (di-isononyl phthalate). DINCH ® is metabolized to its corresponding monoester and subsequently to oxidized monoester derivatives. These are conjugated to glucuronic acid and subject to urinary excretion. In contrast to DINCH ® , there are almost no toxicological data available regarding its primary and secondary metabolites. The present study aimed at the characterization of potential endocrine properties of DINCH ® and five DINCH ® metabolites by using reporter gene assays to monitor the activity of the human nuclear receptors ERα, ERβ, AR, PPARα and PPARγ in vitro. DINCH ® itself did not have any effect on the activity of these receptors whereas DINCH ® metabolites were shown to activate all these receptors. In the case of AR, DINCH ® metabolites predominantly enhanced dihydrotestosterone-stimulated AR activity. In the H295R steroidogenesis assay, neither DINCH ® nor any of its metabolites affected estradiol or testosterone synthesis. In conclusion, primary and secondary DINCH ® metabolites exert different effects at the molecular level compared to DINCH ® itself. All these in vitro effects of DINCH ® metabolites, however, were only observed at high concentrations such as 10 μM or above which is about three orders of magnitude above reported DINCH ® metabolite concentrations in human urine. Thus, the in vitro data do not support the notion that DINCH ® or any of the investigated metabolites may exert considerable endocrine effects in vivo at relevant human exposure levels. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Ra-226 bioaccumulation and growth indices in fish.

    Science.gov (United States)

    Shi, Xiaopei; Smith, Richard; Seymour, Colin; Mothersill, Carmel

    2017-06-01

    To determine the accumulated activity of Ra-226 in fathead minnows fed with environmentally relevant levels of Ra-226 for 5 months in water at 20 °C, and to evaluate the influence of this level of Ra-226 on the growth of fathead minnows. Fathead minnows were fed with fish food containing 10-10,000 mBq/g Ra-226 for 5 months. At the end of the experiment, the fish were sacrificed, flash frozen in liquid nitrogen and kept at -20 °C. Longitudinal sections of 40 μm thickness were cut at the middle of the fish body using a cryostat. The activity of Ra-226 in each section was determined using autoradiography with a nuclear track detector CR-39. According to the weight and the width of the fish, the activity of Ra-226 in the whole fish body could be estimated. In addition, the length and the weight of the fish were measured and the condition factor was calculated to evaluate the growth and fitness of the fish. There is a positive but non-linear relationship between the accumulated activity of Ra-226 in fish body and the concentration of Ra-226 in fish food. The highest activity of Ra-226 accumulated in fish body was found from fish fed with 10,000 mBq/g Ra-226 food. This was calculated as 256.4 ± 49.1 mBq/g, p fish fed with food containing lower concentration of Ra-226 (up to 1000 mBq/g), the bioaccumulation of Ra-226 in the body saturated. The Ra-226 concentration factor (CF) for fish was inversely proportional to the Ra-226 activity in food, and the highest CF value was 2.489, obtained from the lowest dietary Ra-226 activity (10 mBq/g). In addition, condition factors (K) of fish in all Ra-226-treated groups were significantly lower than those of the controls. The results show that the bioaccumulation of Ra-226 in fish is not simply related to the dietary Ra-226 activity, and has a saturation value when the dietary activity is low. In addition, the environmental level of Ra-226 in the fish food has a small adverse effect on the growth and fitness of fathead

  4. Antimicrobial activities of secondary metabolites and phylogenetic study of sponge endosymbiotic bacteria, Bacillus sp. at Agatti Island, Lakshadweep Archipelago

    Directory of Open Access Journals (Sweden)

    Gopi Mohan

    2016-09-01

    Full Text Available Twenty-one species of sponges were recorded under the class of Demospongiae and Calcareous sponges of which 19 species were new to Agatti reef. A total of 113 Sponge endosymbiotic bacterial strains were isolated from twenty-one species of sponges and screened for antimicrobial activity. Five bacterial strains of sponge endosymbiotic bacteria (SEB namely SEB32, SEB33, SEB36, SEB43 and SEB51 showed antimicrobial activity against virulent marine fish pathogens such as Vibrio alginolyticus, Vibrio vulnificus, Vibrio parahaemolyticus, Aeromonas salmonicida, Flavobacterium sp., Edwardsiella sp., Proteus mirabilis and Citrobacter brackii. The secondary metabolites produced by SEB32 from sponge Dysidea fragilis (Montagu, 1818 [48] was selected with broad range of antibacterial activity and subjected for production, characterization by series of chromatography techniques and spectroscopic methods. Based on the results of FT-IR and mass spectrometry, the active molecule was tentatively predicted as “Pyrrol” and the structure is Pyrrolo[1,2-a]pyrazine-1,4-dione, hexahydro- with molecular formula of C7H10N2O2. The LC50 of active molecule was 31 μg/ml and molecular weight of the metabolites was 154. The potential strain SEB32 was identified by gene sequence (GenBank Accession number JX985748 and identified as Bacillus sp. from GenBank database.

  5. Measuring 226Ra and 232Th activity in soil and vegetation samples using a method of double γ-coincidences

    International Nuclear Information System (INIS)

    Antovic, N.M.; Antovic, I.

    2010-01-01

    A coincidence method for measuring radium and thorium activity has been developed using the PRIPYAT-2M gamma-ray coincidence spectrometer, with six NaI(Tl) detectors and registration geometry close to 4π. It was tested by measuring soil samples from the Northern region of Montenegro, as well as vegetation samples from the same region. The results showed a good agreement with ones obtained by the HPGe spectrometer. (author)

  6. The decay scheme of 229Ra

    International Nuclear Information System (INIS)

    Yang, W.F.; Yuan, S.G.; Fang, K.M.; Shen, S.F.; Mou, W.T.; Zhang, X.Q.; Li, Z.Q.

    1997-01-01

    By bombarding the natural thorium targets with 14 MeV neutrons, 229 Ra was produced through the reaction 232 Th(n,α) 229 Ra. The radium activities were separated from the irradiated targets by coprecipitation with the BaCl 2 . A total of 18 new weak γ rays with energies of 14.5, 15.6, 18.8, 21.8, 22.5, 44.0, 47.5, 55.0, 63.0, 69.6, 93.6, 94.1, 98.5, 102.2, 104.5, 106.1, 161.1, and 171.5 keV which could be assigned to the decay of 229 Ra were observed in the isolated radium fractions employing high resolution HPGe detectors and γ(X)-γ coincidence methods. A decay scheme of 229 Ra based on these observations is proposed. (orig.). With 2 figs

  7. Enantioselective biotransformation of propranolol to the active metabolite 4-hydroxypropranolol by endophytic fungi

    Directory of Open Access Journals (Sweden)

    Keyller Bastos Borges

    2011-01-01

    Full Text Available The enantioselective biotransformation of propranolol (Prop by the endophytic fungi Phomopsis sp., Glomerella cingulata, Penicillium crustosum, Chaetomium globosum and Aspergillus fumigatus was investigated by studying the kinetics of the aromatic hydroxylation reaction with the formation of 4-hydroxypropranolol (4-OH-Prop. Both Prop enantiomers were consumed by the fungi in the biotransformation process, but the 4-hydroxylation reaction yielded preferentially (--(S-4-OH-Prop. The quantity of metabolites biosynthesized varied slightly among the evaluated endophytic fungi. These results show that all investigated endophytic fungi could be used as biosynthetic tools in biotransformation processes to obtain the enantiomers of 4-OH-Prop.

  8. Opinion about difficulties of RA reactor operation under conditions of high activity of the heavy water system - Annex 2

    International Nuclear Information System (INIS)

    Nikolic, M.

    1963-01-01

    It was concluded that reactor the reactor operation is very dangerous for the reactor installation as well as safety of the staff under conditions of heavy water increased activity. Two fundamental arguments in favour of this conclusion are: insufficient possibility of reactor components inspection during maintenance and operation in the future period; difficulties in prevention of accidents that could occur is equally dangerous for the reactor facility and the environment. Cleaning and decontamination of the complete heavy water system is needed before the reactor operation starts in order to avoid possible failures or accidental events [sr

  9. The association of fatigue, comorbidity burden, disease activity, disability and gross domestic product in patients with rheumatiod arthritis. Results from 34 countries participating in the Quest-RA programme

    NARCIS (Netherlands)

    Grøn, K.L.; Ørnbjerg, L.M.; Hetland, M.L.; Aslam, F.; Khan, N.A.; Jacobs, J.W.G.; Henrohn, D.; Rasker, Johannes J.; Kauppi, M.J.; Lang, H.C.; Mota, L.M.H.; Aggarwal, A.; Yamanaka, H.; Badsha, H.; Gossec, L.; Cutolo, M.; Ferraccioli, G.; Gremese, E.; Bong Lee, E.; Inanc, N.; Direskeneli, H.; Taylor, Peter; Huisman, Marieke; Alten, R.; Pohl, C.; Oyoo, O.; Stropuviene, S.; Drosos, A.A.; Kerzberg, E.; Ancuta, C.; Mofti, A.; Bergman, M.; Detert, J.; Selim, Z.I.; Abda, E.A.; Rexhepi, B.; Sokka, T.

    2014-01-01

    OBJECTIVES: The aim is to assess the prevalence of comorbidities and to further analyse to which degree fatigue can be explained by comorbidity burden, disease activity, disability and gross domestic product (GDP) in patients with rheumatoid arthritis (RA).METHODS: Nine thousands eight hundred

  10. The association of fatigue, comorbidity burden, disease activity, disability and gross domestic product in patients with rheumatoid arthritis. Results from 34 countries participating in the Quest-RA program

    DEFF Research Database (Denmark)

    Grøn, Kathrine Lederballe; Ornbjerg, Lykke Midtbøll; Hetland, Merete Lund

    2014-01-01

    OBJECTIVES: The aim is to assess the prevalence of comorbidities and to further analyse to which degree fatigue can be explained by comorbidity burden, disease activity, disability and gross domestic product (GDP) in patients with rheumatoid arthritis (RA). METHODS: Nine thousands eight hundred...

  11. Plant Polyphenols and Oxidative Metabolites of the Herbal Alkenylbenzene Methyleugenol Suppress Histone Deacetylase Activity in Human Colon Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Isabel Anna Maria Groh

    2013-01-01

    Full Text Available Evidence has been provided that diet and environmental factors directly influence epigenetic mechanisms associated with cancer development in humans. The inhibition of histone deacetylase (HDAC activity and the disruption of the HDAC complex have been recognized as a potent strategy for cancer therapy and chemoprevention. In the present study, we investigated whether selected plant constituents affect HDAC activity or HDAC1 protein status in the human colon carcinoma cell line HT29. The polyphenols (−-epigallocatechin-3-gallate (EGCG and genistein (GEN as well as two oxidative methyleugenol (ME metabolites were shown to inhibit HDAC activity in intact HT29 cells. Concomitantly, a significant decrease of the HDAC1 protein level was observed after incubation with EGCG and GEN, whereas the investigated ME metabolites did not affect HDAC1 protein status. In conclusion, dietary compounds were found to possess promising HDAC-inhibitory properties, contributing to epigenetic alterations in colon tumor cells, which should be taken into account in further risk/benefit assessments of polyphenols and alkenylbenzenes.

  12. Does a family history of RA influence the clinical presentation and treatment response in RA?

    Science.gov (United States)

    Frisell, Thomas; Saevarsdottir, Saedis; Askling, Johan

    2016-06-01

    To assess whether family history of rheumatoid arthritis (RA), among the strongest risk factors for developing RA, also carries information on the clinical presentation and treatment response. The prospective Swedish Rheumatology register was linked to family history of RA, defined as diagnosed RA in any first-degree relative, ascertained through the Swedish Multi-Generation and Patient registers. Clinical presentation was examined among patients with early RA 2000-2011 (symptom onset clinical characteristics, drug survival, European League Against Rheumatism (EULAR) response and change in disease activity at 3 and 6 months was estimated using linear and generalised logistic regression models. Correlation in relatives' response measures was also assessed. Patients with early RA with family history of RA were more often rheumatoid factor positive, but with no other clinically meaningful differences in their clinical presentation. Family history of RA did not predict response to MTX or TNFi, with the possible exception of no versus good EULAR response to TNFi at 6 months (OR=1.4, 95% CI 1.1 to 1.7). Having a relative who discontinued TNFi within a year increased the odds of doing the same (OR=3.7, 95% CI 1.8 to 7.5), although we found no significant familial correlations in change in disease activity measures. Family history of RA did not modify the clinical presentation of RA or predict response to standard treatment with MTX or TNFi. Treatment response, particularly drug survival, may itself be familial. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  13. In vitro antiprogestational/antiglucocorticoid activity and progestin and glucocorticoid receptor binding of the putative metabolites and synthetic derivatives of CDB-2914, CDB-4124, and mifepristone.

    Science.gov (United States)

    Attardi, Barbara J; Burgenson, Janet; Hild, Sheri A; Reel, Jerry R

    2004-03-01

    In determining the biological profiles of various antiprogestins, it is important to assess the hormonal and antihormonal activity, selectivity, and potency of their proximal metabolites. The early metabolism of mifepristone is characterized by rapid demethylation and hydroxylation. Similar initial metabolic pathways have been proposed for CDB-2914 (CDB: Contraceptive Development Branch of NICHD) and CDB-4124, and their putative metabolites have been synthesized. We have examined the functional activities and potencies, in various cell-based assays, and relative binding affinities (RBAs) for progesterone receptors (PR) and glucocorticoid receptors (GR) of the putative mono- and didemethylated metabolites of CDB-2914, CDB-4124, and mifepristone and of the 17alpha-hydroxy and aromatic A-ring derivatives of CDB-2914 and CDB-4124. The binding affinities of the monodemethylated metabolites for rabbit uterine PR and human PR-A and PR-B were similar to those of the parent compounds. Monodemethylated mifepristone bound to rabbit thymic GR with higher affinity than monodemethylated CDB-2914 or CDB-4124. T47D-CO cells were used to assess inhibition of R5020-stimulated endogenous alkaline phosphatase activity and transactivation of the PRE(2)-thymidine kinase (tk)-luciferase (LUC) reporter plasmid in transient transfections. The antiprogestational potency was as follows: mifepristone/CDB-2914/CDB-4124/monodemethylated metabolites (IC(50)'s approximately 10(-9)M) > aromatic A-ring derivatives (IC(50)'s approximately 10(-8)M) > didemethylated/17alpha-hydroxy derivatives (IC(50)'s approximately 10(-7)M). Antiglucocorticoid activity was determined by inhibition of dexamethasone-stimulated transcriptional activity in HepG2 cells. The mono- and didemethylated metabolites of CDB-2914 and CDB-4124 had less antiglucocorticoid activity (IC(50)'s approximately 10(-6)M) than monodemethylated mifepristone (IC(50) approximately 10(-8)M) or the other test compounds. At 10(-6)M in

  14. Activation of the Silent Secondary Metabolite Production by Introducing Neomycin-Resistance in a Marine-Derived Penicillium purpurogenum G59

    Directory of Open Access Journals (Sweden)

    Chang-Jing Wu

    2015-04-01

    Full Text Available Introduction of neomycin-resistance into a marine-derived, wild-type Penicillium purpurogenum G59 resulted in activation of silent biosynthetic pathways for the secondary metabolite production. Upon treatment of G59 spores with neomycin and dimethyl sulfoxide (DMSO, a total of 56 mutants were obtained by single colony isolation. The acquired resistance of mutants to neomycin was testified by the resistance test. In contrast to the G59 strain, the EtOAc extracts of 28 mutants inhibited the human cancer K562 cells, indicating that the 28 mutants have acquired the capability to produce bioactive metabolites. HPLC-photodiode array detector (PDAD-UV and HPLC-electron spray ionization (ESI-MS analyses further indicated that diverse secondary metabolites have been newly produced in the bioactive mutant extracts. Followed isolation and characterization demonstrated that five bioactive secondary metabolites, curvularin (1, citrinin (2, penicitrinone A (3, erythro-23-O-methylneocyclocitrinol (4 and 22E-7α-methoxy-5α, 6α-epoxyergosta-8(14,22-dien-3β-ol (5, were newly produced by a mutant, 4-30, compared to the G59 strain. All 1–5 were also not yet found in the secondary metabolites of other wild type P. purpurogenum strains. Compounds 1–5 inhibited human cancer K562, HL-60, HeLa and BGC-823 cells to varying extents. Both present bioassays and chemical investigations demonstrated that the introduction of neomycin-resistance into the marine-derived fungal G59 strain could activate silent secondary metabolite production. The present work not only extended the previous DMSO-mediated method for introducing drug-resistance in fungi both in DMSO concentrations and antibiotics, but also additionally exemplified effectiveness of this method for activating silent fungal secondary metabolites. This method could be applied to other fungal isolates to elicit their metabolic potentials to investigate secondary metabolites from silent biosynthetic pathways.

  15. Different effects of clopidogrel and clarithromycin on the enantioselective pharmacokinetics of sibutramine and its active metabolites in healthy subjects.

    Science.gov (United States)

    Shinde, Dhananjay D; Kim, Ho-Sook; Choi, Jae-Seok; Pan, Wei; Bae, Soo Kyung; Yeo, Chang-Woo; Shon, Ji-Hong; Kim, Dong-Hyun; Shin, Jae Gook

    2013-05-01

    In this study, we assessed the effects of clopidogrel and clarithromycin, known CYP2B6 and CYP3A inhibitors, respectively, on the enantioselective disposition of racemic sibutramine in conjunction with CYP2B6 polymorphisms in humans. Sibutramine showed enantioselective plasma profiles with consistently higher concentrations of R-enantiomers. Clopidogrel and clarithromycin significantly increased the sibutramine plasma concentration, but their effects differed between enantiomers; a 2.2-fold versus 4.1-fold increase in the AUC in S-enantiomer and 1.8-fold versus 2.0-fold for the R-enantiomer, respectively. The AUCs of S- and R-desmethyl metabolites changed significantly during the clopidogrel phase (P sibutramine was higher in subjects with the CYP2B6*6/*6 genotype, but no statistical difference was observed among the CYP2B6 genotypes. These results suggest that the enantioselective disposition of sibutramine and its active metabolites are influenced by the altered genetic and environmental factors of CYP2B6 and CYP3A activity in vivo. © The Author(s) 2013.

  16. A new determination method of 226Ra, 224Ra, and 228Th in water

    International Nuclear Information System (INIS)

    Horiuchi, Kimiko; Murakami, Yukio.

    1981-01-01

    A new method for the determination of 226 Ra, 224 Ra and 228 Th in water samples is described. It consists of extraction of 222 Rn and 220 Rn into a scintillator-toluene solution in equilibrium with 226 Ra and 224 Ra and the application of integral counting techniques with a liquid scintillation counter. One liter water sample, weakly acidified with hydrochloric acid, is transferred to a glass bottle, and vigorously bubbled with a stream of nitrogen to expel any radon or thoron in the water sample. Twenty five ml of the scintillator-toluene solution is added to the bottle (time is recorded). The bottle is stoppered with a Teflon stopper and kept at an upside-down position for a given period of time (usually 4 -- 16 days) to allow radon and thoron in partial equilibrium with their parent nuclides. Then, the sample system is vigorously shaken for 2 m and the organic layer is gently transferred to a counting vial through a specially devised transferring tube which is connected to the bottle. The initial counting time is set at 4 h after the separation of organic layer. The measurements are repeated 3 times each immediately and after 106 h from the initial counting time. From these results, the integral counting rates of radon and thoron at the initial counting time are easily obtained. The activities of 226 Ra, 224 Ra and 228 Th in the water sample are calculated from these integral counting rates by the proposed formulas. Some data on the 226 Ra and 224 Ra contents of mineral springs are presented. The lowest detection limits for 226 Ra and 224 Ra were 1.10 x 10 -12 and 1.47 x 10 -9 Ci, respectively. The present method is rapid, easy and accurate and eliminates a time-consuming sealing of the sample in Curie bottle and tedious procedure to transfer the sample gas through a vacuum system to the detector. (author)

  17. RA Research nuclear reactor Part 1, RA Reactor operation and maintenance in 1987; Istrazivacki nuklearni reaktor RA Deo 1 - Pogon i odrzavanje nuklearnog reaktora RA u 1987. godini

    Energy Technology Data Exchange (ETDEWEB)

    Sotic, O; Martinc, R; Cupac, S; Sulem, B; Badrljica, R; Majstorovic, D; Sanovic, V [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

    1987-12-15

    RA research reacto was not operated due to the prohibition issued in 1984 by the Government of Serbia. Three major tasks were finished in order to fulfill the licensing regulations about safety of nuclear facilities which is the condition for obtaining permanent operation licence. These projects involved construction of the emergency cooling system, reconstruction of the existing special ventilation system, and renewal of the system for electric power supply of the reactor systems. Renewal of the RA reactor instrumentation system was initiated. Design project was done by the Russian Atomenergoeksport, and is foreseen to be completed by the end of 1988. The RA reactor safety report was finished in 1987. This annual report includes 8 annexes concerning reactor operation, activities of services and financial issues, and three special annexes: report on testing the emergency cooling system, report on renewal of the RA reactor and design specifications for reactor renewal and reconstruction. [Serbo-Croat] Reaktor RA nije radio usled zabrane Izvsnog veca Skupstine Srbije od 27. avgusta 1984. U cilju povecanja pouzdanosti rada reaktora a da bi se udovoljilo zakonskim propisima sto je uslov za dobijanje stalne dozvole za rad realizovana su tri velika zahvata na reaktoru RA. Ovi zahvati obuhvatili su izgradnju sistema za hladjenje jezgra reaktora u slucaju nuzde, rekonstukciju postojeceg sistema specijalne ventilacije i rekonstrukciju sistema napajanja elektricnom energijom neophodnih potrosaca reaktora RA. Zapoceti su radovi na modernizaciji intrumentacije reaktora RA, projekat je izradjen u sovjetskoj organizaciji Atomenergoeksport, a trebalo bi da se realizuje do kraja 1989. godine. U cilju povecanja prostora za skladistenje ozracenog nuklearnog goriva i njegovog efikasnijeg koriscenja, izradjen je su projekti za rekonstrukciju postojecih uredjaja za rukovanje gorivom, povecanje smestajnog kapaciteta i preciscavanje vode u bazenima za odlezavanje. Realizaija ovih

  18. 226Ra, 228Ra and 40K in scales formed in boilers of industrial installations

    International Nuclear Information System (INIS)

    Poggi, Claudia M. Braga; Farias, Emerson Emiliano G. de; Hazin, Clovis A.; Gazineu, Maria Helena P.; Universidade Catolica de Pernambuco

    2011-01-01

    Many industrial processes involve the production of steam in boilers, which is sent through pipes to machines and other equipment used in different sectors of the installations. The water commonly used in these processes is groundwater, which generally has high concentrations of calcium and magnesium salts, that can co-precipitate with naturally occurring radioactive elements such as 226 Ra and 228 Ra creating radioactive scales, which are deposited in pipes, thus decreasing the efficiency of steam production. In addition, 40 K that is present in all soils and rocks with a concentration of about 0.012% of natural potassium can also be concentrated in these scales. No data was found in literature relating to radionuclides present in the scales formed on boilers in general. In this context, the purpose of this work was to determine concentrations of 226 Ra, 228 Ra and 40 K, in scales generated inside boilers from different industries in the cities of Caruaru, Paulista and Goiana, Pernambuco. Determination of the radionuclides concentration was performed by gamma spectrometry with an HPGe detector, calculating their specific activities. Activity concentrations of 226 Ra were in the range of -1 and 228 Ra activity concentrations varied from 1 . Activity concentrations of 40 K were in the range of -1 . All these activity concentrations were lower than the limits established by the Brazilian Nuclear Energy Commission of for this type of matrix. (author)

  19. Antitumor activity of hierridin B, a cyanobacterial secondary metabolite found in both filamentous and unicellular marine strains.

    Directory of Open Access Journals (Sweden)

    Pedro N Leão

    Full Text Available Cyanobacteria are widely recognized as a valuable source of bioactive metabolites. The majority of such compounds have been isolated from so-called complex cyanobacteria, such as filamentous or colonial forms, which usually display a larger number of biosynthetic gene clusters in their genomes, when compared to free-living unicellular forms. Nevertheless, picocyanobacteria are also known to have potential to produce bioactive natural products. Here, we report the isolation of hierridin B from the marine picocyanobacterium Cyanobium sp. LEGE 06113. This compound had previously been isolated from the filamentous epiphytic cyanobacterium Phormidium ectocarpi SAG 60.90, and had been shown to possess antiplasmodial activity. A phylogenetic analysis of the 16S rRNA gene from both strains confirmed that these cyanobacteria derive from different evolutionary lineages. We further investigated the biological activity of hierridin B, and tested its cytotoxicity towards a panel of human cancer cell lines; it showed selective cytotoxicity towards HT-29 colon adenocarcinoma cells.

  20. Behavior and distribution of 226Ra and 228Ra in the east coast of Peninsular Malaysia marine environment

    International Nuclear Information System (INIS)

    Nurrul Assyikeen Mohd Jaffary; Zal Uyun Wan Mahmood; Zaharudin Ahmad; Yii, Mei Wo; Kamarozaman Ishak

    2010-01-01

    The present distributions of 226 Ra, 228 Ra and activity ratios of 228 Ra/ 226 Ra covering the east coast of Peninsular Malaysia were studied. Sediment core samples were collected at 10 identified stations with the thickness of water column between 14 - 72 m depth during the cruise conducted in 2008. Activity concentrations of 226 Ra and 228 Ra in sediment cores of the studied area were in the range of 18.95 ±4.25 Bq/ kg to 46.48 ± 6.41 Bq/ kg dry wt. and 35.50 ± 7.50 Bq/ kg to 77.10 ±11.37 Bq/ kg dry wt., respectively. Meanwhile, the calculated activity ratios of 228 Ra/ 226 Ra were varied mostly 1.48 to 2.24. The finding showed that there has relationships between 226 Ra, 228 Ra and oceanographic parameters which are can be attributed for better understanding of its transport processes and behavior in the east coast of Peninsular Malaysia marine environment. (author)

  1. Influence of the urine flow rate on some caffeine metabolite ratios used to assess CYP1A2 activity.

    Science.gov (United States)

    Sinués, Blanca; Fanlo, Ana; Bernal, María Luisa; Mayayo, Esteban; Soriano, María Antonia; Martínez-Ballarin, Enrique

    2002-12-01

    Five established metabolite ratios (MRs) to measure P450 CYP1A2 activity--MR1 (17X + 17U)/137X, MR2 (AFMU + 1X + 1U)/17U, MR3 (17X/137X), MR4 (AFMU + 1X + 1U + 17X + 17U)/137X, and MR5 (AFMU + 1X + 1U)/17X--were calculated in urine 4-5 hours after caffeine intake. First, to assess the potential of omeprazole to induce CYP1A2 activity, a caffeine test was performed in 27 subjects on two occasions: before and after 14 days on omeprazole (20 mg/day). Samples of urine were analyzed by high-performance liquid chromatography (HPLC) to quantify caffeine and metabolites used to calculate the different caffeine MRs. MR1, MR3, and MR4 were enhanced after treatment; the percentage of change was inversely associated with that of the urine flow, with r values of -0.48, -0.49, and -0.47, respectively. However, MR2 or MR5 were not modified. To determine the reason for these contradictory results, the authors analyzed data of metabolites, ratios, and their components (numerators and denominators) from 152 subjects (who underwent one caffeine test) and their relationship with the urinary flow. Caffeine concentration in urine was the only compound nondependent on the urine flow. Consistently, ratios containing caffeine (MR1, MR3, and MR4) were highly influenced by the rate of urine excretion, since the flow dependence of their numerators is not canceled out by that of caffeine in their denominators. The dependency of the caffeine excretion on renal factors may explain the opposite results found with the different ratios in the aforementioned prospective study of drug interaction, the absence of closer correlations of the five MRs to each other, the discrepancies about the type of frequency distribution of the different MRs (either normal or multimodal), and the higher sensitivity of MR2 to detect gender differences in CYP1A2 activity found in this study. In summary, the data clearly emphasize the need for a strict control of the liquid intake to avoid high urine flows when MRs

  2. Distinct action of aranidipine and its active metabolite on renal arterioles, with special reference to renal protection.

    Science.gov (United States)

    Nakamura, A; Hayashi, K; Fujiwara, K; Ozawa, Y; Honda, M; Saruta, T

    2000-06-01

    Aranidipine, a newly developed calcium antagonist, possesses unique pharmacologic characteristics in that its metabolite (M-1) still has antihypertensive action. We examined the effects of both agents on renal microcirculation using the isolated perfused hydronephrotic rat kidney. During norepinephrine-induced constriction, the addition of aranidipine dilated both afferent and efferent arterioles in a dose-dependent manner; at 10(-6) M, 83 +/- 6% and 90 +/- 6% reversal, respectively. In contrast, its active metabolite exerted dilator action predominantly on the afferent arteriole (79 +/- 4% vs. 44 +/- 17% at 10(-6) M for afferent and efferent arterioles, respectively). We further examined the long-term (8 weeks) effect of these agents on the development of renal injury in salt-loaded subtotally nephrectomized spontaneously hypertensive rats. Both aranidipine and M-1 reduced blood pressure by a similar magnitude. The decreases in proteinuria were observed in the aranidipine-treated group at weeks 6, 8, and 10, whereas in the M-1 group, significant reduction was attained only at week 6. Histopathologic examination revealed that both treatments improved glomerular and arteriolar sclerosis. Glomerular sclerosis, however, was less pronounced in the aranidipine-treated group than in the M-1 group. In conclusion, aranidipine has dilator action on both arterioles, whereas M-1 caused predominant dilation of afferent arterioles. Such metabolic changes may constitute a determinant of efferent arteriolar action of the calcium antagonist.

  3. Effects of Secondary Plant Metabolites on Microbial Populations: Changes in Community Structure and Metabolic Activity in Contaminated Environments

    Directory of Open Access Journals (Sweden)

    Lucie Musilova

    2016-07-01

    Full Text Available Secondary plant metabolites (SPMEs play an important role in plant survival in the environment and serve to establish ecological relationships between plants and other organisms. Communication between plants and microorganisms via SPMEs contained in root exudates or derived from litter decomposition is an example of this phenomenon. In this review, the general aspects of rhizodeposition together with the significance of terpenes and phenolic compounds are discussed in detail. We focus specifically on the effect of SPMEs on microbial community structure and metabolic activity in environments contaminated by polychlorinated biphenyls (PCBs and polyaromatic hydrocarbons (PAHs. Furthermore, a section is devoted to a complex effect of plants and/or their metabolites contained in litter on bioremediation of contaminated sites. New insights are introduced from a study evaluating the effects of SPMEs derived during decomposition of grapefruit peel, lemon peel, and pears on bacterial communities and their ability to degrade PCBs in a long-term contaminated soil. The presented review supports the “secondary compound hypothesis” and demonstrates the potential of SPMEs for increasing the effectiveness of bioremediation processes.

  4. Light-induced biochemical variations in secondary metabolite production and antioxidant activity in callus cultures of Stevia rebaudiana (Bert).

    Science.gov (United States)

    Ahmad, Naveed; Rab, Abdur; Ahmad, Nisar

    2016-01-01

    Stevia rebaudiana (S. rebaudiana) is a very important species with worldwide medicinal and commercial uses. Light is one of the major elicitors that fluctuate morphogenic potential and biochemical responses. In the present study, we investigated the effect of various spectral lights on biomass accumulation and secondary metabolite production in callus cultures of S. rebaudiana. Leaf explants were placed on Murashige and Skoog (MS) medium and exposed to various spectral lights. 6-Benzyle adenine (BA) and 2, 4-dichlorophenoxy acetic acid (2, 4-D; 2.0 mgl(-1)) were used for callus induction. The control light (16/8h) produced optimum callogenic response (92.73%) than other colored lights. Compared to other colored lights, control grown cultures displayed maximum biomass accumulation (5.78 gl(-1)) during a prolonged log phase at the 18th day of growth kinetics. Cultures grown under blue light enhanced total phenolic content (TPC; 102.32 μg/g DW), total flavonoid content (TFC; 22.07 μg/g DW) and total antioxidant capacity (TAC; 11.63 μg/g DW). On the contrary, green and red lights improved reducing power assay (RPA; 0.71Fe(II)g(-1) DW) and DPPH-radical scavenging activity (DRSA; 80%). Herein, we concluded that the utilization of colored lights is a promising strategy for enhanced production of antioxidant secondary metabolites in callus cultures of S. rebaudiana. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Metabolite profiling, antioxidant, and α-glucosidase inhibitory activities of germinated rice: nuclear-magnetic-resonance-based metabolomics study

    Directory of Open Access Journals (Sweden)

    Phaiwan Pramai

    2018-01-01

    Full Text Available In an attempt to profile the metabolites of three different varieties of germinated rice, specifically black (GBR, red, and white rice, a 1H-nuclear-magnetic-resonance-based metabolomics approach was conducted. Multivariate data analysis was applied to discriminate between the three different varieties using a partial least squares discriminant analysis (PLS-DA model. The PLS model was used to evaluate the relationship between chemicals and biological activities of germinated rice. The PLS-DA score plot exhibited a noticeable separation between the three rice varieties into three clusters by PC1 and PC2. The PLS model indicated that α-linolenic acid, γ-oryzanol, α-tocopherol, γ-aminobutyric acid, 3-hydroxybutyric acid, fumaric acid, fatty acids, threonine, tryptophan, and vanillic acid were significantly correlated with the higher bioactivities demonstrated by GBR that was extracted in 100% ethanol. Subsequently, the proposed biosynthetic pathway analysis revealed that the increased quantities of secondary metabolites found in GBR may contribute to its nutritional value and health benefits.

  6. Effect of CYP2B6 genotype on the pharmacokinetics of sibutramine and active metabolites in healthy subjects.

    Science.gov (United States)

    Chung, Jae Yong; Jang, Seong Bok; Lee, Yoon Jung; Park, Min Soo; Park, Kyungsoo

    2011-01-01

    Sibutramine is a pharmacologic intervention for the treatment of obesity. The effect of CYP2B6 genotypes on the pharmacokinetics of sibutramine and its active metabolites (desmethylsibutramine [M1] and didesmethylsibutramine [M2]) was evaluated in 57 healthy subjects. Each subject received a single oral dose of 10 or 15 mg sibutramine, and blood samples were collected up to 72 hours after dosing. The relationship between the genotypes and the pharmacokinetics of sibutramine, M1, and M2 was examined. A statistically significant difference in the elimination half-life (t(1/2)) of sibutramine M1 was found among the 3 genotype groups (P = .0006), between the *1/*1 and *1/*6 groups (P = .0001), and between the *1/*4 and *1/*6 groups (P = .012). The mean value of M1 t(1/2) in *1/*6 (33.3 ± 10.5 hours) was about 58% and 61% greater than that of the *1/*1 group (21.0 ± 7.4 hours) and the *1/*4 group (20.7 ± 9.8 hours), respectively. No significant differences in area under the concentration-time curve or maximum plasma drug concentration were observed between the groups. The CYP2B6*6 allele may be associated with a lower metabolic clearance of the M1 metabolite of sibutramine in human subjects.

  7. Changes of Enzymes Activity and Production of Secondary Metabolites of Artemisia aucheri in Different Altitudes and Its Relation to Adaptation

    Directory of Open Access Journals (Sweden)

    Hassan Zare-maivan

    2014-08-01

    Full Text Available Artemisia plants are the most abundant plants species in Iran which contain strong antioxidant properties and as such, have medicinal and economic value. Despite wide distribution of Artemisisa species, ecophysiology of its adaptation to changes in altitude and soil property had not been investigated. In this study, the relationships between ecophysiological and adaptation capabilities of A. aucheri to altitude changes through measuring changes in the activity of its antioxidant enzymes and secondary metabolites in situ was investigated based on a completely randomized experiment. The enzyme activities of superoxide dismutase, catalase, peroxidase, and the amount of total phenolics, flavonoids, anthocyanins, malondialdehyde and chlorophylls A and B were measured in A. aucheri plants growing in three different altitudes at and above the 36° latitude on the southern slopes of Eastern Alborz Mountain ranges in triplicate 10*10 m quadrates. Statistical analysis of data showed that soil type was loamy significantly becoming more sandy- loam with lowering in altitude and the soil contained greater amounts of oxides of silicone, aluminum, magnesium, sodium, potassium and phosphorus in upper altitude except calcium which was present in greater quantity in lower altitude. With increasing altitude, activity of superoxide dismutase and quantities of chlorophylls and total phenols in leaves increased. Some biochemical factors in A. aucheri showed significant positive correlation(P ≤ 0.05 between them. Adaptation of A. aucheri to changes in altitude occurred through changing its antioxidant enzymes activity and production of secondary metabolites in response to factors related to the altitude including soil type and texture, moisture level, temperature and most importantly radiation

  8. Alpha-particle doses to human organs and tissues from internally-deposited 226Ra and 228Ra

    International Nuclear Information System (INIS)

    Keane, A.T.; Schlenker, R.A.

    1981-01-01

    Estimation of radiation doses to the soft tissues from internally-deposited 226 Ra and 228 Ra is relevant to an investigation of soft-tissue malignancies in radium-exposed persons being conducted at the Center for Human Radiobiology. Alpha-particle doses in a 50-year period following a single injection of 226 Ra or 228 Ra are presented for 31 soft tissues and organs of the adult human. The dose estimates were derived from the ICRP alkaline earth model fitted to data on retention of 226 Ra in soft tissues and bone, combined with reported ratios of 226 Ra to Ca in soft tissue and bone at natural levels and the distribution of Ca in the tissues of Reference Man (ICRP23). The median of the 31 organ and tissue doses from the α-particles of 226 Ra itself is 0.08 rad per injected μCi. An additional average dose of 0.01 rad per μCi 226 Ra daughter products produced in soft tissue or transferred from bone to soft tissue. Soft-tissue doses from α-particles of the 228 Ra decay series are about six times those from 226 Ra α-particles for equal injected activities of 228 Ra and 226 Ra, with the assumption that 228 Ra daughter products do not transfer from the organ in which they are produced. The 50-year dose to the red marrow of bone from α-particles originating in bone is 0.55 rad per μCi 226 Ra injected and 1.0 rad per μCi 228 Ra injected. For ingestion by dial painters of luminous compound containg 226 Ra or 228 Ra with a daughter-to-parent activity ratio of 0.5, the dose to the mucosal alyer of the lower large intestine from α-particles originating in the gut contents is about 0.1 rad per μCi systemic intake of 226 Ra or 228 Ra

  9. Atividade do sistema antioxidante e desenvolvimento de aerênquima em raízes de milho 'Saracura' Antioxidant system activity and aerenchyma formation in 'Saracura' maize roots

    Directory of Open Access Journals (Sweden)

    Fabricio José Pereira

    2010-05-01

    Full Text Available Este trabalho teve como objetivo avaliar a influência de sucessivos ciclos de seleção do milho 'Saracura' na atividade das enzimas do sistema antioxidante, e a relação dessas enzimas com a capacidade dessa variedade em desenvolver aerênquima. Sementes de 18 ciclos de seleção intercalados do milho 'Saracura' e da cultivar BR 107, sensível à hipoxia, foram semeadas em vasos e em casa de vegetação. As plantas foram submetidas ao alagamento intermitente de dois em dois dias. As amostras de raízes foram coletadas após 60 dias e analisaram-se as atividades das enzimas peroxidase do guaiacol, peroxidase do ascorbato e catalase, além da capacidade das plantas de cada ciclo desenvolverem aerênquima. Ao longo dos ciclos, as plantas apresentaram modificações na atividade das enzimas, com aumento na de peroxidase do ascorbato e diminuição na de catalase e de peroxidase do guaiacol. Observou-se, ainda, maior capacidade de desenvolver aerênquima nos últimos ciclos de seleção. A redução na atividade das enzimas do sistema antioxidante parece estar relacionada a um desbalanço na decomposição de H2O2.This work aimed to assess the influence of successive selection cycles in 'Saracura' maize on the enzyme activity of the antioxidant system and the relationship of these enzymes with the aerenchyma development capacity of this variety. Seeds of 18 intercalated selection cycles of the 'Saracura' maize and of the cultivar BR 107, sensitive to hipoxia, were sown in pots in the greenhouse. Plants were submitted to intermittent soil flooding each two days. After 60 days, the roots were sampled and analysis were done for the guaiacol peroxidase, ascorbate peroxidase, and catalase activities and for the capacity of the plants of each cycle to develop aerenchyma. The plants showed modifications in enzyme activity along the cycles, increasing the ascorbate peroxidase activity and decreasing the catalase and guaiacol peroxidase ones. A greater

  10. Virtual Cross-Linking of the Active Nemorubicin Metabolite PNU-159682 to Double-Stranded DNA.

    Science.gov (United States)

    Scalabrin, Matteo; Quintieri, Luigi; Palumbo, Manlio; Riccardi Sirtori, Federico; Gatto, Barbara

    2017-02-20

    The DNA alkylating mechanism of PNU-159682 (PNU), a highly potent metabolite of the anthracycline nemorubicin, was investigated by gel-electrophoretic, HPLC-UV, and micro-HPLC/mass spectrometry (MS) measurements. PNU quickly reacted with double-stranded oligonucleotides, but not with single-stranded sequences, to form covalent adducts which were detectable by denaturing polyacrylamide gel electrophoresis (DPAGE). Ion-pair reverse-phase HPLC-UV analysis on CG rich duplex sequences having a 5'-CCCGGG-3' central core showed the formation of two types of adducts with PNU, which were stable and could be characterized by micro-HPLC/MS. The first type contained one alkylated species (and possibly one reversibly bound species), and the second contained two alkylated species per duplex DNA. The covalent adducts were found to produce effective bridging of DNA complementary strands through the formation of virtual cross-links reminiscent of those produced by classical anthracyclines in the presence of formaldehyde. Furthermore, the absence of reactivity of PNU with CG-rich sequence containing a TA core (CGTACG), and the minor reactivity between PNU and CGC sequences (TACGCG·CGCGTA) pointed out the importance of guanine sequence context in modulating DNA alkylation.

  11. Corporal mass index and body image perception by women attending at health and physical activity office of “Raúl Sánchez” polyclinic

    Directory of Open Access Journals (Sweden)

    Dianelys Ledesma-Beades

    2015-06-01

    Full Text Available The corporal image is the mental representation of the body that each individual builds. The dissatisfaction with the image and the corporal mass is closely associated to the self-esteem of the women. According to researches there are many concerned and insecure women in relation to their own shapes with a high index of corporal dissatisfaction, constituting a world problem. A high index of women goes to the physical activity and health consultation that Raúl Sánchez policlinic of Pinar del Río; offers many of them, for their dissent with the corporal weight. For this reason, we decide to carry out a research with the objective of determining the existent relationship between the CMI and the perception of the corporal image in women that attend to this consultation during the year 2014. It is a descriptive transverse study with a sample of 102 women older than 15 years old. They were carried out measured (weigh corporal and stature and a questionnaire was made to establish the grade of corporal dissatisfaction. It was used the questionnaire proposed by Stunkard, constituted by ten silhouettes for the feminine gender, numbered and ordained for the selection of one of them, that according to her perception and pleasure, it corresponded to her current corporal image and to how they wanted to be. The obtained data were tabulated and represented by means of charts. It was concluded that a high percent of these women is perceived incorrectly: 0,98% is undernourished and 62,8%, fatter; that the women with values of real CMI corresponding with normal weight and overweight are fatter than they really are, while the obese ones are perceived thinner; they consider that the pregnancies have been the main cause of the changes in the corporal weight and their grade of corporal dissatisfaction is based on 70,6% by their appearance before the society.

  12. VELoCiRaPTORS.

    Science.gov (United States)

    Lundgren, J.; Esham, B.; Padalino, S. J.; Sangster, T. C.; Glebov, V.

    2007-11-01

    The Venting and Exhausting of Low Level Air Contaminants in the Rapid Pneumatic Transport of Radioactive Samples (VELoCiRaPTORS) system is constructed to transport radioactive materials quickly and safely at the NIF. A radioactive sample will be placed inside a carrier that is transported via an airflow system produced by controlled differential pressure. Midway through the transportation process, the carrier will be stopped and vented by a powered exhaust blower which will remove radioactive gases within the transport carrier. A Geiger counter will monitor the activity of the exhaust gas to ensure that it is below acceptable levels. If the radiation level is sufficient, the carrier will pass through the remainder of the system, pneumatically braking at the counting station. The complete design will run manually or automatically with control software. Tests were performed using an inactive carrier to determine possible transportation problems. The system underwent many consecutive trials without failure. VELoCiRaPTORS is a prototype of a system that could be installed at both the Laboratory for Laser Energetics at the University of Rochester and the National Ignition Facility at LLNL.

  13. Research nuclear reactor RA, Annual Report 2001

    International Nuclear Information System (INIS)

    Sotic, O.

    2002-01-01

    During 2001, activities at the RA research nuclear reactor in were performed according to the Contract about financing of the RA reactor for the period January-December 2001, signed by the Ministry of Science, technology and development of the Republic of Serbia. RA reactor was not operated since shutdown in August 1984. Although, the most of the planned reconstruction activities were finished until 1991, the most important, which was concerned with exchange of the reactor instrumentation, financed by the IAEA, was interrupted due to international sanctions imposed on the country. Since 1992, all the renewal and reconstruction activities were ceased. Continuous aging and degradation of the equipment and facilities demand decision making about the future status of the Ra reactor. Until this decision is made it is an obligation to maintain control and maintenance of ventilation system, power supply, internal transportation system, spent fuel storage, hot cells, electronic fuel surveillance system, and part of the stationary dosimetry system. In 2001, apart from the mentioned activities, actions were undertaken related to maintenance of the reactor building and installations. The most important tasks fulfilled were: protection of the roof of the ventilation system building, purchase and installing the fire protection system and twelve new battery cells in the reactor building. There were no actions concerned with improvement of the conditions for intermediate spent fuel storage. With the support of IAEA, actions were initiated for possible transport of the spent fuel tu Russia. At the end of 2001, preparations were started for possible future decommissioning of the RA reactor. After, renewal of the membership of our country in the IAEA, the Government of Yugoslavia has declared its attitude about the intention of RA reactor decommissioning at the General Conference in September 2001 [sr

  14. Concentration of natural radionuclides (40K, 228Ra and 226Ra) in vegetables and fruits collected around Kudankulam, South India

    International Nuclear Information System (INIS)

    Mahiban Ross, E.; Feroz Khan, M.; Lenin Raj, Y.; Godwin Wesley, S.; Kumar, M.; Sundar Rajan, P.

    2007-01-01

    Baseline activity concentration of the natural radio nuclides 40 K, 228 Ra and 226 Ra in vegetables and fruits was determined around Kudankulam. In many of the samples, 228 Ra and 226 Ra was below minimum detection limit. 40 K was found to be more in leafy vegetables followed by pods, tubers and fleshy fruits. The highest accumulator among the matrices was the leafy vegetables with the geometric mean of 189.47 Bq.kg -1 fresh for vegetables and fruits with the geometric mean of 128.95 Bq.kg -1 fresh. 228 Ra activity in vegetables and fruits ranged from 0.074 to 1.153 and 0.074 to 0.131 Bq.kg -l fresh respectively. 226 Ra in vegetables and fruits ranged from BDL to 0.07 and BDL-.044 Bq.kg -l fresh respectively. 40 K in vegetables and fruits followed a log normal distribution. (author)

  15. Seasonal variation of 228Ra/226Ra ratio in seaweed: implications for water circulation patterns in coastal areas of the Noto Peninsula, Japan

    International Nuclear Information System (INIS)

    Inoue, M.; Kofuji, H.; Yamamoto, M.; Komura, K.

    2005-01-01

    To examine water circulation patterns of coastal water, 72 seaweed (Sargasso) samples and 27 coastal water samples were collected from coastal areas of the Noto Peninsula, Japan, during the period from December 1998 to June 2002. The 228 Ra and 226 Ra activities of those samples were measured by low-background γ-ray spectrometry. There was a wide range of activities of 228 Ra (0.5-2 Bq/kg-fresh) and 226 Ra (0.5-1.2 Bq/kg-fresh) in the Sargasso samples. The 228 Ra/ 226 Ra activity ratio of Sargasso samples exhibited seasonal variation with minimum values in June ( 228 Ra/ 226 Ra = ∼1) and maximum values in December (1.5-2.5), which was mainly governed by changes in 228 Ra activity. It is also notable that the seasonal variation of the 228 Ra/ 226 Ra ratio of Sargasso is in approximate agreement with that of the ambient coastal water. Sargasso samples appear to have retained the 228 Ra/ 226 Ra ratio of the ambient coastal waters, and the temporal variations in that ratio provide insight into seasonal changes in water circulation in the Noto Peninsula coastal area

  16. RA Research nuclear reactor Part 1, RA Reactor operation and maintenance in 1987

    International Nuclear Information System (INIS)

    Sotic, O.; Martinc, R.; Cupac, S.; Sulem, B.; Badrljica, R.; Majstorovic, D.; Sanovic, V.

    1987-01-01

    RA research reacto was not operated due to the prohibition issued in 1984 by the Government of Serbia. Three major tasks were finished in order to fulfill the licensing regulations about safety of nuclear facilities which is the condition for obtaining permanent operation licence. These projects involved construction of the emergency cooling system, reconstruction of the existing special ventilation system, and renewal of the system for electric power supply of the reactor systems. Renewal of the RA reactor instrumentation system was initiated. Design project was done by the Russian Atomenergoeksport, and is foreseen to be completed by the end of 1988. The RA reactor safety report was finished in 1987. This annual report includes 8 annexes concerning reactor operation, activities of services and financial issues, and three special annexes: report on testing the emergency cooling system, report on renewal of the RA reactor and design specifications for reactor renewal and reconstruction [sr

  17. The combination of glutamate receptor antagonist MK-801 with tamoxifen and its active metabolites potentiates their antiproliferative activity in mouse melanoma K1735-M2 cells

    International Nuclear Information System (INIS)

    Ribeiro, Mariana P.C.; Nunes-Correia, Isabel; Santos, Armanda E.; Custódio, José B.A.

    2014-01-01

    Recent reports suggest that N-methyl-D-aspartate receptor (NMDAR) blockade by MK-801 decreases tumor growth. Thus, we investigated whether other ionotropic glutamate receptor (iGluR) antagonists were also able to modulate the proliferation of melanoma cells. On the other hand, the antiestrogen tamoxifen (TAM) decreases the proliferation of melanoma cells, and is included in combined therapies for melanoma. As the efficacy of TAM is limited by its metabolism, we investigated the effects of the NMDAR antagonist MK-801 in combination with TAM and its active metabolites, 4-hydroxytamoxifen (OHTAM) and endoxifen (EDX). The NMDAR blockers MK-801 and memantine decreased mouse melanoma K1735-M2 cell proliferation. In contrast, the NMDAR competitive antagonist APV and the AMPA and kainate receptor antagonist NBQX did not affect cell proliferation, suggesting that among the iGluR antagonists only the NMDAR channel blockers inhibit melanoma cell proliferation. The combination of antiestrogens with MK-801 potentiated their individual effects on cell biomass due to diminished cell proliferation, since it decreased the cell number and DNA synthesis without increasing cell death. Importantly, TAM metabolites combined with MK-801 promoted cell cycle arrest in G1. Therefore, the data obtained suggest that the activity of MK-801 and antiestrogens in K1735-M2 cells is greatly enhanced when used in combination. - Highlights: • MK-801 and memantine decrease melanoma cell proliferation. • The combination of MK-801 with antiestrogens inhibits melanoma cell proliferation. • These combinations greatly enhance the effects of the compounds individually. • MK-801 combined with tamoxifen active metabolites induces cell cycle arrest in G1. • The combination of MK-801 and antiestrogens is an innovative strategy for melanoma

  18. 228Ra and 226Ra measurement on a BaSO4 co-precipitation source

    International Nuclear Information System (INIS)

    Medley, Peter; Martin, Paul; Bollhöfer, Andreas; Parry, David

    2015-01-01

    One of the most commonly-used methods for determination of 226 Ra, particularly in water samples, utilises co-precipitation of Ra with BaSO 4 , followed by microfiltration to produce a source for alpha counting. This paper describes two extensions to BaSO 4 co-precipitation methods which enable determination of 228 Ra using the same source. The adaptations presented here do not introduce any contaminants that will affect the separation of radium or alpha counting for 226 Ra, and can be used for re-analysis of already existing sources prepared by BaSO 4 co-precipitation. The first adaptation uses detection of 228 Ac on the source by gamma spectrometry. The detection efficiency is high, allowing analysis of water samples at sufficiently low activity to be suitable in testing for compliance with drinking water quality standards. As 228 Ac grows in quickly, taking less than 2 days to reach equilibrium with the 228 Ra parent, this can also be useful in radiological emergency response situations. The second adaptation incorporates a method for the digestion of BaSO 4 sources, allowing separation of thorium and subsequent determination of 228 Th activity. Although ingrowth periods for 228 Th can be lengthy, very low detection limits for 228 Ra can be achieved with this technique. - Highlights: • We developed two methods for 228 Ra measurement on Ba(Ra)SO 4 co-precipitation sources. • Measurement by gamma spectrometry using the daughter 228 Ac is rapid. • Detection limits are suitable for assessment of drinking water quality. • The second approach uses alpha spectrometry on a separated Th fraction. • This is more sensitive than gamma spectrometry after an ingrowth period greater than about 1 month

  19. Measurement and Analysis of Specific Activities of Natural Radionuclides (40K, 226Ra and 232Th) in Beach Sand Samples from Talo Kapo Beach of Yaring District in Pattani Province using Gamma Ray Spectrometry

    Science.gov (United States)

    Daoh, M.; Masae, R. N.; Po-oh, S.; Boonkrongcheep; Kessaratikoon, P.

    2017-09-01

    The Specific Activities of 40K, 226Ra and 232Th were studied and determinate for 30 beach sand samples collected from Talo Kapo beach of Yaring district in Pattani province. Experimental results were obtained by using a high-purity germanium (HPGe) detector and gamma spectrometry analysis system. The IAEA-SOIL-6 reference materials obtained from the International Atomic Energy Agency were also used to analyze and compute the 40K, 226Ra and 232Th specific activity in all 30 beach sand samples. The measuring time of each sample is 10,000 seconds. It was found that specific activity range from 1805.37 - 3323.05, 40.96 - 2137.36 38.63 - 4329.28 Bq/kg for with mean values of 2242.79 ± 117.40, 250.18 ± 8.21 and 458.42 ± 7.68 Bq/kg for 40K, 226Ra and 232Th, respectively. Moreover, the results were also compared with research data in the south of Thailand, the Office of Atoms for Peace (OAP) annual report data and the recommended values which were proposed by United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR,)

  20. RA Research nuclear reactor - Annual report 1987; Istrazivacki nuklearni reaktor RA - Izvestaj o radu za 1987. godinu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1987-12-15

    Annual report concerning the project 'RA research nuclear reactor' for 1987, financed by the Serbian ministry of science is divided into two parts. First part is concerned with RA reactor operation and maintenance, which is the task of the Division for reactor engineering of the Institute for multidisciplinary studies and RA reactor engineering. Second part deals with radiation protection activities at the RA reactor which is the responsibility of the Institute for radiation protection. Scientific council of the Institute for multidisciplinary studies and RA reactor engineering has stated that this report describes adequately the activity and tasks fulfilled at the RA reactor in 1989. The scope and the quality of the work done were considered successful both concerning the maintenance and reconstruction, as well as radiation protection activities. [Serbo-Croat] Godisnji izvestaj po projektu 'Istrazivacki nuklearni reaktor RA' za 1987. godinu, koji finansira republicka zajednica za nauku SR Srbije po ugovoru br. 3509/1 sastoji se iz dva dela. Prvi deo obuhvata pogon i odrzavanje nuklearnog reaktora RA, sto predstavlja obavezu Odeljenja za reaktorski inzenjering u sastavu OOUR Instituta za multidisciplinarna istrazivanja i inzenjering RA. Drugi deo obuhvata poslove zastite od zracenja na reaktoru RA, sto predstavlja obavezu OOUR Instituta za zastitu od zracenja 'Zastita'. Naucno vece Instituta za multidisciplinarna istrazivanja i inzenjjring RA ocenilo je da sadrzina ovog izvestaja odgovara izvrsenim poslovima na reaktoru RA u 1989. godini. Pozitivno se ocenjuje obim i kvalitet izvrsenih radova kako u pogledu odrzavanja i rekonstrukcije reaktora, tako i u pogledu poslova zastite od zracenja izvrsenih kod njega.

  1. RA radiological characterization database application

    International Nuclear Information System (INIS)

    Steljic, M.M; Ljubenov, V.Lj. . E-mail address of corresponding author: milijanas@vin.bg.ac.yu; Steljic, M.M.)

    2005-01-01

    Radiological characterization of the RA research reactor is one of the main activities in the first two years of the reactor decommissioning project. The raw characterization data from direct measurements or laboratory analyses (defined within the existing sampling and measurement programme) have to be interpreted, organized and summarized in order to prepare the final characterization survey report. This report should be made so that the radiological condition of the entire site is completely and accurately shown with the radiological condition of the components clearly depicted. This paper presents an electronic database application, designed as a serviceable and efficient tool for characterization data storage, review and analysis, as well as for the reports generation. Relational database model was designed and the application is made by using Microsoft Access 2002 (SP1), a 32-bit RDBMS for the desktop and client/server database applications that run under Windows XP. (author)

  2. [Biological activity of metabolites of the herb Kalanchoe diagremontania (Hamet de la Bbathie) Jacobs et Perr].

    Science.gov (United States)

    Anisimov, M M; Gerasimenko, N I; Chaĭkina, E L; Serebriakov, Iu M

    2009-01-01

    In this study we investigated the hemolytic, antimicrobial, and phytoregulatory activity of various classes of lipids (triacylglycerols, free fatty acids (FFA), the glyceroglycolipids monogalactosyl diacylglycerol (MGDG), sulfoquinovosyl diacylglycerol (SQDG)), sterols, all of them were obtained from the medical herb Kalanchoe diagremontiana, and also pigments, phenolic compounds (FC), polysaccharides, and ethanol extract (EE) of the herbal. It was established that EE, FC, FFA, and sterols display pH-dependent membranothropic activity. FFA showed antimicrobial activity and stimulated growth of buckwheat stalk sprouts. K. diagremontiana glyceroglycolopids did not display expressed biological activity. Caroteniods displayed pH-independent membranothopic action and antibacterial activity. Chlorophylls displayed antimicrobial action, but did not influence erythrocytes and buckwheat sprouts. Polysaccharides acted against the microorganisms Safale S-04, Candida albicans, Fusarium oxysperum and buckwheat sprouts.

  3. Identification of Minor Secondary Metabolites from the Latex of Croton lechleri (Muell-Arg and Evaluation of Their Antioxidant Activity

    Directory of Open Access Journals (Sweden)

    Maria Iorizzi

    2008-06-01

    Full Text Available Dragon’s blood (Sangre de drago, a viscous red sap derived from Croton lechleri Muell-Arg (Euphorbiaceae, is extensively used by indigenous cultures of the Amazonian basin for its wound healing properties. The aim of this study was to identify the minor secondary metabolites and test the antioxidant activity of this sustance. A bioguided fractionation of the n-hexane, chloroform, n-butanol, and aqueous extracts led to the isolation of 15 compounds: three megastigmanes, four flavan-3-ols, three phenylpropanoids, three lignans, a clerodane, and the alkaloid taspine. In addition to these known molecules, six compounds were isolated and identified for the first time in the latex: blumenol B, blumenol C, 4,5-dihydroblumenol A, erythro-guaiacyl-glyceryl-β-O-4’- dihydroconiferyl ether, 2-[4-(3-hydroxypropyl-2-methoxyphenoxy]-propane-1,3-diol and floribundic acid glucoside. Combinations of spectroscopic methods (1H-, 13C- NMR and 2D-NMR experiments, ESI-MS, and literature comparisons were used for compound identification. In vitro antioxidant activities were assessed by DPPH, total antioxidant capacity and lipid peroxidation assays. Flavan-3-ols derivatives (as major phenolic compounds in the latex exhibited the highest antioxidant activity.

  4. Investigation on the Metabolic Regulation of pgi gene knockout Escherichia coli by Enzyme Activities and Intracellular Metabolite Concentrations

    Directory of Open Access Journals (Sweden)

    Nor ‘Aini, A. R.

    2006-01-01

    Full Text Available An integrated analysis of the cell growth characteristics, enzyme activities, intracellular metabolite concentrations was made to investigate the metabolic regulation of pgi gene knockout Escherichia coli based on batch culture and continuous culture which was performed at the dilution rate of 0.2h-1. The enzymatic study identified that pathways of pentose phosphate, ED pathway and glyoxylate shunt were all active in pgi mutant. The glycolysis enzymes i.e glyceraldehyde-3-phosphate dehydrogenase, fructose diphosphatase, pyruvate kinase, triose phosphate isomerase were down regulated implying that the inactivation of pgi gene reduced the carbon flux through glycolytic pathway. Meanwhile, the pentose phosphate pathway was active as a major route for intermediary carbohydrate metabolism instead of glycolysis. The pentose phosphate pathway generates most of the major reducing co-factor NADPH as shown by the increased of NADPH/NADP+ ratio in the mutant when compared with the parent strain. The fermentative enzymes such as acetate kinase and lactate dehydrogenase were down regulated in the mutant. Knockout of pgi gene results in the significant increase in the intracellular concentration of glucose-6-phosphate and decrease in the concentration of oxaloacetate. The slow growth rate of the mutant was assumed to be affected by the accumulation of glucose-6-phosphate and imbalance of NADPH reoxidation.

  5. Anticancer Activity of Ramalin, a Secondary Metabolite from the Antarctic Lichen Ramalina terebrata, against Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sung-Suk Suh

    2017-08-01

    Full Text Available Colorectal cancer is a leading cause of death worldwide and occurs through the highly complex coordination of multiple cellular pathways, resulting in carcinogenesis. Recent studies have increasingly revealed that constituents of lichen extracts exhibit potent pharmaceutical activities, including anticancer activity against various cancer cells, making them promising candidates for new anticancer therapeutic drugs. The main objective of this study was to evaluate the anticancer capacities of ramalin, a secondary metabolite from the Antarctic lichen Ramalina terebrata, in the human colorectal cancer cell line HCT116. In this study, ramalin displayed concentration-dependent anticancer activity against HCT116 cells, significantly suppressing proliferation and inducing apoptosis. Furthermore, ramalin induced cell cycle arrest in the gap 2/mitosis (G2/M phase through the modulation of hallmark genes involved in the G2/M phase transition, such as tumour protein p53 (TP53, cyclin-dependent kinase inhibitor 1A (CDKN1A, cyclin-dependent kinase 1 (CDK1 and cyclin B1 (CCNB1. At both the transcriptional and translational level, ramalin caused a gradual increase in the expression of TP53 and its downstream gene CDKN1A, while decreasing the expression of CDK1 and CCNB1 in a concentration-dependent manner. In addition, ramalin significantly inhibited the migration and invasion of colorectal cancer cells in a concentration-dependent manner. Taken together, these data suggest that ramalin may be a therapeutic candidate for the targeted therapy of colorectal cancer.

  6. SU-F-T-57: Delivered Activity Accuracy of Radium 223 Dichloride Injections, When Being Administrated for Castration Resistant Prostate Cancer, Symptomatic Bone Metastases. The Impact of Residual Activity in the Spent Syringe and Dispensing Accuracy of Ra 223

    International Nuclear Information System (INIS)

    Jennings, G

    2016-01-01

    Purpose: To quantify the delivered activity accuracy of Radium 223 dichloride injections, when being administrated for castration – resistant prostate cancer, symptomatic bone metastases. The impact of residual activity in the spent syringe and dispensing accuracy of Ra 223. Methods: The administration is by slow intravenous injection over 1 minute followed by double flushing of the 10 mL syringe and IV with saline. Eighty (80) procedures was used to investigate variations in the activity from the amount prescribed (µCi) = 1.35 × Patient weight Kg. The Activity dispensed into a 10mL syringe using a NIST traceable Capintec CRC-25R Chamber and a cross calibrated capintec CRC-15R to measure activity in the syringe immediately before and after administration Results: The patients weight range from 121Ib to 235lb and doses ranging 74.25 µCi to 144.2 µCi. The deviation of dispensed dose vs Prescribed dose average +2.1% with a range of −1.1% to +5.7%. The Dose measured before administration ranges 79.3 µCi to 154.9 µCi. Deviation from the dispensed dose was show to average +2.9% with a range of −0.8% to +7.3%. The average residual dose post injection was 2.5 µCi or 2.2% of the pre injection activity. Ranging from 0.9 µCi to 6.2 µCi, 0.7% to 5.4% respectively. Subtracting the residual activity from that measured activity before injection and comparing it to prescription dose was shown to have an average variation of +2.7% with a range of −0.8% to 7.4%. Conclusion: The case resulted in the 6.2 µCi maximum residual dose had two syringes. A small, 82.8 µCi activity, case resulted in the 7.4% maximum variation in measures less residual verses prescription dose. The average +2.1 % dispenses activity of Ra 223 over the prescription dosage was seen to counteract the average 2.2% residual dosage found to remain in the syringe

  7. SU-F-T-57: Delivered Activity Accuracy of Radium 223 Dichloride Injections, When Being Administrated for Castration Resistant Prostate Cancer, Symptomatic Bone Metastases. The Impact of Residual Activity in the Spent Syringe and Dispensing Accuracy of Ra 223

    Energy Technology Data Exchange (ETDEWEB)

    Jennings, G [Marsden Medical Physics Associates, Denville, NJ (United States)

    2016-06-15

    Purpose: To quantify the delivered activity accuracy of Radium 223 dichloride injections, when being administrated for castration – resistant prostate cancer, symptomatic bone metastases. The impact of residual activity in the spent syringe and dispensing accuracy of Ra 223. Methods: The administration is by slow intravenous injection over 1 minute followed by double flushing of the 10 mL syringe and IV with saline. Eighty (80) procedures was used to investigate variations in the activity from the amount prescribed (µCi) = 1.35 × Patient weight Kg. The Activity dispensed into a 10mL syringe using a NIST traceable Capintec CRC-25R Chamber and a cross calibrated capintec CRC-15R to measure activity in the syringe immediately before and after administration Results: The patients weight range from 121Ib to 235lb and doses ranging 74.25 µCi to 144.2 µCi. The deviation of dispensed dose vs Prescribed dose average +2.1% with a range of −1.1% to +5.7%. The Dose measured before administration ranges 79.3 µCi to 154.9 µCi. Deviation from the dispensed dose was show to average +2.9% with a range of −0.8% to +7.3%. The average residual dose post injection was 2.5 µCi or 2.2% of the pre injection activity. Ranging from 0.9 µCi to 6.2 µCi, 0.7% to 5.4% respectively. Subtracting the residual activity from that measured activity before injection and comparing it to prescription dose was shown to have an average variation of +2.7% with a range of −0.8% to 7.4%. Conclusion: The case resulted in the 6.2 µCi maximum residual dose had two syringes. A small, 82.8 µCi activity, case resulted in the 7.4% maximum variation in measures less residual verses prescription dose. The average +2.1 % dispenses activity of Ra 223 over the prescription dosage was seen to counteract the average 2.2% residual dosage found to remain in the syringe.

  8. CYP2C19*17 increases clopidogrel-mediated platelet inhibition but does not alter the pharmacokinetics of the active metabolite of clopidogrel

    DEFF Research Database (Denmark)

    Pedersen, Rasmus Steen; Nielsen, Flemming; Stage, Tore Bjerregaard

    2014-01-01

    *1/*1, 11 CYP2C19*1/*17 and nine CYP2C19*17/*17). In Phase A, the pharmacokinetics of the derivatized active metabolite of clopidogrel (CAMD) and platelet function were determined after administration of a single oral dose of 600 mg clopidogrel (Plavix; Sanofi-Avensis, Horsholm, Denmark). In Phase B...

  9. α-Glucosidase Inhibition and Antibacterial Activity of Secondary Metabolites from the Ecuadorian Species Clinopodium taxifolium (Kunth Govaerts

    Directory of Open Access Journals (Sweden)

    Vladimir Morocho

    2018-01-01

    Full Text Available The phytochemical investigation of both volatile and fixed metabolites of Clinopodium taxifolium (Kunth Govaerts (Lamiaceae was performed for the first time. It allowed the isolation and characterization of the essential oil and six known compounds: carvacrol (1, squalane (2, uvaol (3, erythrodiol (4, ursolic acid (5, and salvigenin (6. Their structures were identified and characterized by Nuclear Magnetic Resonance (NMR and Gas Chromatography coupled to Mass Spectroscopy (GC-MS, and corroborated by literature. The essential oil of the leaves was obtained by hydrodistillation in two different periods and analyzed by GC-MS and GC coupled to Flame Ionization Detector (GC-FID. A total of 54 compounds were detected, of which 42 were identified (including trace constituents. The major constituents were carvacrol methyl ether (18.9–23.2%, carvacrol (13.8–16.3% and, carvacryl acetate (11.4–4.8%. The antibacterial activities were determined as Minimum Inhibition Concentration (MIC against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa and Micrococcus luteus. The hexane and methanol extracts exhibited activity only against Klebsiella pneumoniae (250 and 500 μg/mL respectively, while the ethyl acetate extract was inactive. The hypoglycemic activity was evaluated by the in vitro inhibition of α-glucosidase. The ethyl acetate (EtOAc extract showed strong inhibitory activity with IC50 = 24.88 µg/mL, however methanolic and hexanic extracts showed weak activity. As a pure compound, only ursolic acid showed a strong inhibitory activity, with IC50 = 72.71 μM.

  10. A validated HPLC-MS/MS assay for quantifying unstable pharmacologically active metabolites of clopidogrel in human plasma: application to a clinical pharmacokinetic study.

    Science.gov (United States)

    Furlong, Michael T; Savant, Ishani; Yuan, Moucun; Scott, Laura; Mylott, William; Mariannino, Thomas; Kadiyala, Pathanjali; Roongta, Vikram; Arnold, Mark E

    2013-05-01

    Clopidogrel is prescribed for the treatment of Acute Coronary Syndrome and recent myocardial infarction, recent stroke, or established peripheral arterial disease. A sensitive and reliable high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay was developed and validated to enable reliable quantification of four diastereomeric and chemically reactive thiol metabolites, two of which are pharmacologically active, in human plasma. The metabolites were stabilized by alkylation of their reactive thiol moieties with 2-bromo-3'-methoxyacetophenone (MPB). Following organic solvent mediated-protein precipitation in a 96-well plate format, chromatographic separation was achieved by gradient elution on an Ascentis Express RP-amide column. Chromatographic conditions were optimized to ensure separation of the four derivatized active metabolites. Derivatized metabolites and stable isotope-labeled internal standards were detected by positive ion electrospray tandem mass spectrometry. The HPLC-MS/MS assay was validated over concentration ranges of 0.125-125 ng/mL for metabolites H1-H3 and 0.101-101 ng/mL for H4. Intra- and inter-assay precision values for replicate quality control samples were within 14.3% for all analytes during the assay validation. Mean quality control accuracy values were within ±6.3% of nominal values for all analytes. Assay recoveries were high (>79%). The four derivatized analytes were stable in human blood for at least 2 h at room temperature and on ice. The analytes were also stable in human plasma for at least 25 h at room temperature, 372 days at -20 °C and -70 °C, and following at least five freeze-thaw cycles. The validated assay was successfully applied to the quantification of all four thiol metabolites in human plasma in support of a human pharmacokinetic study. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Effect of thiamethoxam on cockroach locomotor activity is associated with its metabolite clothianidin.

    Science.gov (United States)

    Benzidane, Yassine; Touinsi, Sarra; Motte, Emilie; Jadas-Hécart, Alain; Communal, Pierre-Yves; Leduc, Lionel; Thany, Steeve H

    2010-12-01

    In the present study, the effect of thiamethoxam and clothianidin on the locomotor activity of American cockroach, Periplaneta americana (L.), was evaluated. Because it has been proposed that thiamethoxam is metabolised to clothianidin, high-performance liquid chromatography coupled with mass spectrometry was used to evaluate the amount of clothianidin on thiamethoxam-treated cockroaches. One hour after neonicotinoid treatment, the time spent in the open-field-like apparatus significantly increased, suggesting a decrease in locomotor activity. The percentage of cockroaches displaying locomotor activity was significantly reduced 1 h after haemolymph application of 1 nmol g(-1) neonicotinoid, while no significant effect was found after topical and oral administration. However, at 24 and 48 h, all neonicotinoids were able to reduce locomotor activity, depending on their concentrations and the way they were applied. Interestingly, it was found that thiamethoxam was converted to clothianidin 1 h after application, but the amount of clothianidin did not rise proportionately to thiamethoxam, especially after oral administration. The data suggest that the effect of thiamethoxam on cockroach locomotor activity is due in part to clothianidin action because (1) thiamethoxam levels remained persistent 48 h after application and (2) the amount of clothianidin in cockroach tissues was consistent with the toxicity of thiamethoxam. Copyright © 2010 Society of Chemical Industry.

  12. Research nuclear reactor RA - Annual Report 1991

    International Nuclear Information System (INIS)

    Sotic, O.

    1992-01-01

    Activities related to revitalisation of the RA reactor stared in 1986, were continued in 1991. A number of interventions on the reactor components were finished that are supposed to enable continuous and reliable operation. The last, and at the same time largest action, related to exchange of complete reactor instrumentation is underway, but it is behind the schedule in 1991 because the delivery of components from USSR is late. Production of this instruments is financed by the IAEA according to the contract signed in December 1988 with Russian Atomenergoexport. According to this contract, it has been planned that the RA reactor instrumentation should be delivered to the Vinca Institute by the end of 1990. Only 56% of the instrumentation was delivered until September 1991. Since then any delivery of components to Yugoslavia was stopped because of the temporary embargo imposed by the IAEA. In 1991 most of the existing RA reactor instrumentation was dismantled, only the part needed for basic measurements when reactor is not operated, was maintained. Construction of some support elements is almost finished by the local staff. The Institute has undertaken this activity in order to speed up the ending of the project. If all the planned instrumentation would not arrive until the end of March 1992, it would not be possible to start the RA reactor testing operation in the first part of 1993, as previously planned. In 1991, 53 staff members took part in the activities during 1991, which is considered sufficient for maintenance and repair conditions. Research reactor RA Annual report for year 1991 is divided into two main parts to cover: (1) operation and maintenance and (2) activities related to radiation protection [sr

  13. GABAA receptor activity modulating piperine analogs: In vitro metabolic stability, metabolite identification, CYP450 reaction phenotyping, and protein binding.

    Science.gov (United States)

    Zabela, Volha; Hettich, Timm; Schlotterbeck, Götz; Wimmer, Laurin; Mihovilovic, Marko D; Guillet, Fabrice; Bouaita, Belkacem; Shevchenko, Bénédicte; Hamburger, Matthias; Oufir, Mouhssin

    2018-01-01

    In a screening of natural products for allosteric modulators of GABA A receptors (γ-aminobutyric acid type A receptor), piperine was identified as a compound targeting a benzodiazepine-independent binding site. Given that piperine is also an activator of TRPV1 (transient receptor potential vanilloid type 1) receptors involved in pain signaling and thermoregulation, a series of piperine analogs were prepared in several cycles of structural optimization, with the aim of separating GABA A and TRPV1 activating properties. We here investigated the metabolism of piperine and selected analogs in view of further cycles of lead optimization. Metabolic stability of the compounds was evaluated by incubation with pooled human liver microsomes, and metabolites were analyzed by UHPLC-Q-TOF-MS. CYP450 isoenzymes involved in metabolism of compounds were identified by reaction phenotyping with Silensomes™. Unbound fraction in whole blood was determined by rapid equilibrium dialysis. Piperine was the metabolically most stable compound. Aliphatic hydroxylation, and N- and O-dealkylation were the major routes of oxidative metabolism. Piperine was exclusively metabolized by CYP1A2, whereas CYP2C9 contributed significantly in the oxidative metabolism of all analogs. Extensive binding to blood constituents was observed for all compounds. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Dynamics of the Content of Lactobacilli, Microbial Metabolites and Antimicrobial Activity of Growing Culture of Lactobacillus Plantarum 8P-A3

    Directory of Open Access Journals (Sweden)

    I. Yu. Chicherin

    2013-01-01

    Full Text Available The dynamics of the content of lactobacilli, microbial metabolites and antimicrobial activity of growing cultures of Lactobacillus plantarum 8Р-А3 was studied. Lactobacilli L. plantarum 8Р-А3 and test microorganisms isolated from the intestinal contents of patients with dysbacteriosis were used in experiments. Study of the component composition of growing culture supernatant of lactobacilli was carried out by gas liquid chromatography with mass selective detection. By 54 h of cultivation the content of viable microbial cells in the native culture of Lactobacillus achieves 3,0·109 in 1 mL without further increase during the cultivation. The principal component of lactobacilli culture medium possessing antibacterial activity is lactic acid. In addition to lactic acid, which accounts for 70% of the total metabolites, the culture medium and the supernatant contain salts of phosphoric acid (14% as well as amino acids, carboxylic acids, fatty acids, sugars and polyhydric alcohol constituting of up to 16% of the total metabolites. It is found that during the cultivation in liquid medium lactobacilli produce metabolites which possess antibacterial activity against pathogenic bacteria that cause intestinal infections.

  15. RA Reactor operation and maintenance (I-IX), part VII, Task 3.08/04, Refurbishment of the RA reactor

    International Nuclear Information System (INIS)

    Zecevic, V.

    1963-12-01

    This volume covers the following reports concerned with the maintenance and repair work of the RA reactor: repair of the technical water system; maintenance of the transportation equipment; vacuuming and drying during refurbishment; repair and decontamination of the distillation device; and the report on participation of the operational dosimetry division in the RA reactor refurbishment activities

  16. Biotransformation of fluoroquinolone antibiotics by ligninolytic fungi - Metabolites, enzymes and residual antibacterial activity

    Czech Academy of Sciences Publication Activity Database

    Čvančarová, Monika; Moeder, M.; Filipová, Alena; Cajthaml, Tomáš

    2015-01-01

    Roč. 136, OCT 2015 (2015), s. 311-320 ISSN 0045-6535 R&D Projects: GA TA ČR TE01020218; GA ČR GA13-28283S Institutional support: RVO:61388971 Keywords : Fluoroquinolone antibiotics * White rot fungi * Residual antibacterial activity Subject RIV: EE - Microbiology, Virology Impact factor: 3.698, year: 2015

  17. Salicylate, diflunisal and their metabolites inhibit CBP/p300 and exhibit anticancer activity.

    Science.gov (United States)

    Shirakawa, Kotaro; Wang, Lan; Man, Na; Maksimoska, Jasna; Sorum, Alexander W; Lim, Hyung W; Lee, Intelly S; Shimazu, Tadahiro; Newman, John C; Schröder, Sebastian; Ott, Melanie; Marmorstein, Ronen; Meier, Jordan; Nimer, Stephen; Verdin, Eric

    2016-05-31

    Salicylate and acetylsalicylic acid are potent and widely used anti-inflammatory drugs. They are thought to exert their therapeutic effects through multiple mechanisms, including the inhibition of cyclo-oxygenases, modulation of NF-κB activity, and direct activation of AMPK. However, the full spectrum of their activities is incompletely understood. Here we show that salicylate specifically inhibits CBP and p300 lysine acetyltransferase activity in vitro by direct competition with acetyl-Coenzyme A at the catalytic site. We used a chemical structure-similarity search to identify another anti-inflammatory drug, diflunisal, that inhibits p300 more potently than salicylate. At concentrations attainable in human plasma after oral administration, both salicylate and diflunisal blocked the acetylation of lysine residues on histone and non-histone proteins in cells. Finally, we found that diflunisal suppressed the growth of p300-dependent leukemia cell lines expressing AML1-ETO fusion protein in vitro and in vivo. These results highlight a novel epigenetic regulatory mechanism of action for salicylate and derivative drugs.

  18. Bioactive metabolite profiles and antimicrobial activity of ethanolic extracts from Muntingia calabura L. leaves and stems

    Directory of Open Access Journals (Sweden)

    William Patrick Cruiz Buhian

    2016-08-01

    Conclusions: M. calabura leaf and stem ethanol extracts are potential sources of antibacterial agents against P. aeruginosa and S. aureus. This study reports for the first time the high degree of antifungal activity of M. calabura ethanolic extract, especially against C. albicans.

  19. Production of Some Biologically Active Secondary Metabolites From Marine-derived Fungus Varicosporina ramulosa

    Directory of Open Access Journals (Sweden)

    Atalla, M. M.

    2008-01-01

    Full Text Available In a screening of fungal isolates associated with marine algae collected from Abou-keer, Alexanderia during the four seasons of 2004, to obtain new biologically active compounds. Varicosporina ramulosa isolate was identified and selected as a producer of 13 compounds. Out of 13 pure compounds produced, compounds 3 and 10 were considered as antibacterial and antifungal compounds, respectively as they were active against gram positive, gram negative bacteria and a fungus. Optimization of conditions (fermentation media, incubation period, temperature, initial pH, aeration levels which activate compounds 3 and 10 production were studied. Also the spectral properties (UV, MS, GC/MS, IR and 1H-NMR of the purified compounds were determined. Compound 3 suggested to be dibutyl phthalate and compound 10 may be ergosterol or one of its isomers. Biological evaluation of the two compounds towards 6 different types of tumor cell lines showed weak effect of compound 3 at different concentrations on the viable cell count of the different tumor cell lines. While compound 10 showed different activities against the viable cell count of the 6 different tumor cell lines. It kills 50% of the viable infected liver and lung cells at concentrations equal to 99.7 µg/mL, 74.9µg/mL, respectively. Compound 10 can be recommended as new anticancer compounds.

  20. Activation of the nuclear receptor PPARgamma by metabolites isolated from sage (Salvia officinalis L.)

    DEFF Research Database (Denmark)

    Christensen, K B; Jørgensen, M.; Kotowska, D

    2010-01-01

    ETHNOPHARMACOLOGICAL RELEVANCE: Salvia officinalis has been used as a traditional remedy against diabetes in many countries and its glucose-lowering effects have been demonstrated in animal studies. The active compounds and their possible mode of action are still unknown although it has been sugg...

  1. The effect of Chitosan on antioxidant activity and some secondary metabolites of Mentha piperita L.

    Directory of Open Access Journals (Sweden)

    Sima Salimgandomi

    2016-09-01

    Full Text Available Plants are almost reach sources of phenolic compounds such as flavonoids which are the most important natural antioxidants. Antioxidant compounds are essential for protecting human body against oxidative stress. However use elicitors could increase the antioxidant activity of plant. The purpose of this study was to evaluate the effects of Chitosan on the content of phenolic and flavonoid compounds and also antioxidant activity Mentha piperita L.In this study, firstly the Mentha piperita L. were grown up for 6-week period at greenhouse conditions and then were treated with 50-100 μm of chitosan, then total phenolic and flavonoid contents were determined using spectrophotometry and finally antioxidant activities of extracts were evaluated with 2,2-diphenyl-1-picryl hydrazyl (DPPH method and the results were analyzed with Excel software and Variance analysis testing method with SPSS software. The results showed the content of phenolic compounds in the methanol extract based on sample mg of Gallic acid /g for control with water, 50μm and 100μm treatments respectively were 146.8,233.1,339.1. Meanwhile the total volume of flavonoid content of the methanol extract per mg of Rutin/g respectively were 9.88,12.11,14.06 and concentration of the said extracts respectively were 196.3,147.7,128.62. In regard to the above results it can be concluded that due to having phenolic and flavonoid contents, Mentha piperita L showed that antioxidant activity could be stimulated upon Chitosan treatment moreover, antioxidant activity increased by increasing Chitosan treatment content. Therefore, this method can be used to increase antioxidant effect of plant as a natural antioxidant and all the phenolic and flavonoid contents.

  2. Secondary Metabolites from Vietnamese Marine Invertebrates with Activity against Trypanosoma brucei and T. cruzi

    Directory of Open Access Journals (Sweden)

    Nguyen Phuong Thao

    2014-06-01

    Full Text Available Marine-derived natural products from invertebrates comprise an extremely diverse and promising source of the compounds from a wide variety of structural classes. This study describes the discovery of five marine natural products with activity against Trypanosoma species by natural product library screening using whole cell in vitro assays. We investigated the anti-trypanosomal activity of the extracts from the soft corals and echinoderms living in Vietnamese seas. Of the samples screened, the methanolic extracts of several marine organisms exhibited potent activities against cultures of Trypanosoma brucei and T. cruzi (EC50 < 5.0 μg/mL. Among the compounds isolated from these extracts, laevigatol B (1 from Lobophytum crassum and L. laevigatum, (24S-ergost-4-ene-3-one (2 from Sinularia dissecta, astropectenol A (3 from Astropecten polyacanthus, and cholest-8-ene-3β,5α,6β,7α-tetraol (4 from Diadema savignyi showed inhibitory activity against T. brucei with EC50 values ranging from 1.57 ± 0.14 to 14.6 ± 1.36 μM, relative to the positive control, pentamidine (EC50 = 0.015 ± 0.003 μM. Laevigatol B (1 and 5α-cholest-8(14-ene-3β,7α-diol (5 exhibited also significant inhibitory effects on T. cruzi. The cytotoxic activity of the pure compounds on mammalian cells was also assessed and found to be insignificant in all cases. This is the first report on the inhibitory effects of marine organisms collected in Vietnamese seas against Trypanosoma species responsible for neglected tropical diseases.

  3. In vitro antioxidant capacity and free radical scavenging evaluation of active metabolite constituents of Newbouldia laevis ethanolic leaf extract.

    Science.gov (United States)

    Habu, Josiah Bitrus; Ibeh, Bartholomew Okechukwu

    2015-03-14

    The aim of the present study was to evaluate the in vitro antioxidant and free radical scavenging capacity of bioactive metabolites present in Newbouldia laevis leaf extract. Chromatographic and spectrophotometric methods were used in the study and modified where necessary in the study. Bioactivity of the extract was determined at 10 μg/ml, 50 μg/ml, 100 μg/ml, 200 μg/ml and 400 μg/ml concentrations expressed in % inhibition. The yield of the ethanolic leaf extract of N.laevis was 30.3 g (9.93%). Evaluation of bioactive metabolic constituents gave high levels of ascorbic acid (515.53 ± 12 IU/100 g [25.7 mg/100 g]), vitamin E (26.46 ± 1.08 IU/100 g), saponins (6.2 ± 0.10), alkaloids (2.20 ± 0.03), cardiac glycosides(1.48 ± 0.22), amino acids and steroids (8.01 ± 0.04) measured in mg/100 g dry weight; moderate levels of vitamin A (188.28 ± 6.19 IU/100 g), tannins (0.09 ± 0.30), terpenoids (3.42 ± 0.67); low level of flavonoids (1.01 ± 0.34 mg/100 g) and absence of cyanogenic glycosides, carboxylic acids and aldehydes/ketones. The extracts percentage inhibition of DPPH, hydroxyl radical (OH.), superoxide anion (O2 .-), iron chelating, nitric oxide radical (NO), peroxynitrite (ONOO-), singlet oxygen (1O2), hypochlorous acid (HOCl), lipid peroxidation (LPO) and FRAP showed a concentration-dependent antioxidant activity with no significant difference with the controls. Though, IC50 of the extract showed significant difference only in singlet oxygen (1O2) and iron chelating activity when compared with the controls. The extract is a potential source of antioxidants/free radical scavengers having important metabolites which maybe linked to its ethno-medicinal use.

  4. Non-invasive monitoring of adrenocortical activity in captive African Penguin (Spheniscus demersus) by measuring faecal glucocorticoid metabolites.

    Science.gov (United States)

    Ozella, L; Anfossi, L; Di Nardo, F; Pessani, D

    2015-12-01

    Measurement of faecal glucocorticoid metabolites (FGMs) has become a useful and widely-accepted method for the non-invasive evaluation of stress in vertebrates. In this study we assessed the adrenocortical activity of five captive African Penguins (Spheniscus demersus) by means of FGM evaluation following a biological stressor, i.e. capture and immobilization. In addition, we detected individual differences in secretion of FGMs during a stage of the normal biological cycle of penguins, namely the breeding period, without any external or induced causes of stress. Our results showed that FGM concentrations peaked 5.5-8h after the induced stress in all birds, and significantly decreased within 30 h. As predictable, the highest peak of FGMs (6591 ng/g) was reached by the youngest penguin, which was at its first experience with the stressor. This peak was 1.8-2.7-fold higher compared to those of the other animals habituated to the stimulus. For the breeding period, our results revealed that the increase in FGMs compared to ordinary levels, and the peaks of FGMs, varied widely depending on the age and mainly on the reproductive state of the animal. The bird which showed the lowest peak (2518 ng/g) was an old male that was not in a reproductive state at the time of the study. Higher FGM increases and peaks were reached by the two birds which were brooding (male: 5552%, 96,631 ng/g; female: 1438%, 22,846 ng/g) and by the youngest bird (1582%, 39,700 ng/g). The impact of the reproductive state on FGM levels was unexpected compared to that produced by the induced stress. The EIA used in this study to measure FGM levels proved to be a reliable tool for assessing individual and biologically-relevant changes in FGM concentrations in African Penguin. Moreover, this method allowed detection of physiological stress during the breeding period, and identification of individual differences in relation to the reproductive status. The increase in FGM levels as a response to capture and

  5. Transfer of 226Ra, 228Ra, 210Pb and 210Po in aquatic organisms and food chain

    International Nuclear Information System (INIS)

    Yang Xiaotong; Weng Detong; Chen Wenyin; Chen Xiuyun; Chen Jixi; Zhao Shimin

    1998-01-01

    Objective: To find out the transfer regularities of 226 Ra, 228 Ra, 210 Pb and 210 Po, which are natural radionuclides in the aquatic organisms and food chain. Methods: Large amount of breed of representative aquatic products and their living waters and sediments were collected and treated according to routine experimental procedures. The contents of 226 Ra, 228 Ra, 210 Pb and 210 Po were detected in each sample. Measured data were analyzed statistically and pairwise comparisons were made to determine the differences between groups. Results: 226 Ra, 228 Ra and 210 Pb were mainly deposited in the bones (or shells), their concentration factors (CF) ranged from 10 2 to 10 3 ; the CF ranged only from 10 0 to 10 2 in the flesh. 210 Po was mainly deposited in the soft tissues, CF ranged from 10 2 to 10 4 ; especially in the stomachs and intestines of fishes, the value reached 10 4 . The cooking process did not impinge significantly on the transfer of 226 Ra, 228 Ra and 210 Pb in the food chain (P>0.05), but did significantly influence the transfer of 210 Po, especially in the freshwater fishes and shrimps. Paired comparison test of the activities between raw flesh and cooked flesh showed very significant difference (P 226 Ra, 228 Ra, 210 Pb and 210 Po. Even though the bones (or shells) of aquatic organisms contained relatively higher levels of 226 Ra, 228 Ra and 210 Pb, the cooking process does not significantly increase the radioactive contents in the foodstuffs. However, the cooking process does significantly influence the transfer of 210 Po. It does significantly increase the content of 210 Po in foodstuffs

  6. Morphine metabolites

    DEFF Research Database (Denmark)

    Christrup, Lona Louring

    1997-01-01

    , morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) are the major metabolites of morphine. The metabolism of morphine occurs not only in the liver, but may also take place in the brain and the kidneys. The glucuronides are mainly eliminated via bile and urine. Glucuronides as a rule...... are considered as highly polar metabolites unable to cross the blood-brain barrier. Although morphine glucuronidation has been demonstrated in human brain tissue, the capacity is very low compared to that of the liver, indicating that the M3G and M6G concentrations observed in the cerebrospinal fluid (CSF) after...... systemic administration reflect hepatic metabolism of morphine and that the morphine glucuronides, despite their high polarity, can penetrate into the brain. Like morphine, M6G has been shown to be relatively more selective for mu-receptors than for delta- and kappa-receptors while M3G does not appear...

  7. Evaluation of antifungal metabolites activity from bacillus licheniformis OE-04 against Colletotrichum gossypii.

    Science.gov (United States)

    Nawaz, Hafiz Husnain; Nelly Rajaofera, M J; He, Qiguang; Anam, Usmani; Lin, Chunhua; Miao, Weiguo

    2018-04-01

    Anthracnose disease in the cotton plant caused by fungal pathogen Colletotrichum gossypii. It is supposed to be most critical diseases in the cotton crop as it causes infection and leads to complete damaging of the cotton crop by infecting the leaves, stems, and bolls in the field. The disease control is challenging due to the absence of an effective fungicide without damaging the farmer health and environment. So the series of experiments were designed to assess the antagonistic activity of biosurfactant released by strain Bacillus licheniformis OE-04 against the anthracnose causing agent in cotton and this strain was screened out from forty eight strain of rhizobacteria. We also estimated the heat stability and pH range and toxicity of biosurfactant produced by strain 0E-04. The results showed that biosurfactant has maximum antifungal activity against C. gossypii. In vitro study concluded that the biosurfactant can reduce fungal activity by inhibiting the spore germination of C. gossypii. Moreover, the biosurfactant also has wide pH and temperature range. We observed Antifungal activity of biosurfactant at 5 to 10 pH range and temperature range was also wide from room temperature to 100 °C. We also observed the toxicity of biosurfactant produced by Bacillus licheniformis against zebra fish (Danio rerio). We were noticed that biosurfactant have least harmful effect with maximum concentration. The study confirmed that biosurfactant of Bacillus licheniformis have high pH and heat stability range with least harmful effects so it can be a good replacement of chemical pesticides for cotton anthracnose control. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Antifungal Activity Against Plant Pathogens of Metabolites from the Endophytic Fungus Cladosporium cladosporioides

    OpenAIRE

    Wang, Xiaoning; Radwan, Mohamed M.; Taráwneh, Amer H.; Gao, Jiangtao; Wedge, David E.; Rosa, Luiz H.; Cutler, Horace G.; Cutler, Stephen J.

    2013-01-01

    Bioassay-guided fractionation of Cladosporium cladosporioides (Fresen.) de Vries extracts led to the isolation of four compounds, including cladosporin, 1, isocladosporin, 2, 5′-hydroxyasperentin, 3, and cladosporin-8-methyl ether, 4. An additional compound 5′,6-diacetyl cladosporin, 5, was synthesized by acetylation of compound 3. Compounds 1-5 were evaluated for antifungal activity against plant pathogens. Phomopsis viticola was the most sensitive fungus to the tested compounds. At 30 μM, c...

  9. In vitro effects of brominated flame retardants and metabolites on CYP17 catalytic activity: A novel mechanism of action?

    International Nuclear Information System (INIS)

    Canton, Rocio F.; Sanderson, J. Thomas; Nijmeijer, Sandra; Bergman, Ake; Letcher, Robert J.; Berg, Martin van den

    2006-01-01

    Fire incidents have decreased significantly over the last 20 years due, in part, to regulations requiring addition of flame retardants (FRs) to consumer products. Five major classes of brominated flame retardants (BFRs) are hexabromocyclododecane isomers (HBCDs), tetrabromobisphenol-A (TBBPA) and three commercial mixtures of penta-, octa- and deca-polybrominated diphenyl ether (PBDE) congeners, which are used extensively as commercial FR additives. Furthermore, concentrations of PBDEs have been rapidly increasing during the 1999s in human breast milk and a number of endocrine effects have been reported. We used the H295R human adrenocortical carcinoma cell line to assess possible effects of some of these BFRs (PBDEs and several of their hydroxylated (OH) and methoxylated (CH 3 O) metabolites or analogues), TBBPA and brominated phenols (BPs) on the combined 17α-hydroxylase and 17,20-lyase activities of CYP17. CYP17 enzyme catalyzes an important step in sex steroidogenesis and is responsible for the biosynthesis of dehydroepiandrosterone (DHEA) and androstenedione in the adrenals. In order to study possible interactions with BFRs, a novel enzymatic method was developed. The precursor substrate of CYP17, pregnenolone, was added to control and exposed H295R cells, and enzymatic production of DHEA was measured using a radioimmunoassay. In order to avoid pregnenolone metabolism via different pathways, specific chemical inhibitor compounds were used. None of the parent/precursor BFRs had a significant effect (P 3 O group eliminated this cytotoxic effect, but CYP17 activity measured as DHEA production was still significantly inhibited. Other OH- or CH 3 O-PBDE analogues were used to elucidate possible structural properties behind this CYP17 inhibition and associated cytotoxicity, but no distinct structure activity relationship could be determined. These in vitro results indicate that OH and CH 3 O-PBDEs have potential to interfere with CYP17 activity for which the in vivo

  10. Antioxidant activity and concentration of secondary metabolites in the plant parts of Euphorbia cyparissias L.

    Directory of Open Access Journals (Sweden)

    Stanković Milan S.

    2014-01-01

    Full Text Available This paper presents the results of a screening of nine different extracts from the plant parts (leaves, flowers and stems of Euphorbia cyparissias for total phenolic content, concentration of flavonoids and in vitro antioxidant activity. Main reason for this study is the determination of these parameters and their variability among plant parts and plant extracts obtained by different solvents, respectively. Obtained amounts for total phenolic content ranged from 10.76 to 40.72 mg GA/g. The concentration of flavonoids varied from 34.32 to 134.34 mg Ru/g. The IC50 values of antioxidant activity varied from 88.48 to 2891.08 μg/ml. Results obtained from the different plant parts were of uneven value. Great variability of the studied parameters was observed when comparing the effectiveness of the used solvents. The acetone extracts from stems contain the greatest concentrations of phenolic compounds, especially flavonoids, and showed high antioxidant activity. According to our research, plant parts from E. cyparissias can be regarded as promising candidates for natural plant sources with high value of biological compounds.

  11. The Content of Secondary Metabolites and Antioxidant Activity of Wild Strawberry Fruit (Fragaria vesca L.

    Directory of Open Access Journals (Sweden)

    Magdalena Dyduch-Siemińska

    2015-01-01

    Full Text Available Chemical analyses carried out in 2011–2013 aimed at evaluating the contents of flavonoids, free phenolic acids, tannins, anthocyanins, and antioxidant activity (% by means of DPPH radical neutralization ability in fresh and air-dried fruits of three wild strawberry cultivars. Examinations revealed differences in contents of biologically active substances determined in raw versus dried material depending on the cultivar. Mean concentrations of flavonoids and tannins were highest in raw fruits of “Baron von Solemacher” cv., which amounted to 1.244 mg·g−1 and 6.09%, respectively. Fresh fruits of “Regina” cv. were characterized by the highest average content of phenolic acids and anthocyanins: 4.987 mg·g−1 and 0.636 mg·100 g−1. The pattern of mean contents of biologically active substances analyzed in air-dried fruits was similar. Significant differences in abilities to neutralize the DPPH radical to diphenylpicrylhydrazine by extracts made of examined wild strawberry fruits were also indicated.

  12. Opinion about difficulties of RA reactor operation under conditions of high activity of the heavy water system - Annex 2; Prilog 2 - Misljenje o teskocama eksploatacije reaktora RA u uslovima visoke aktivnosti teskovodnog sistema

    Energy Technology Data Exchange (ETDEWEB)

    Nikolic, M [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

    1963-12-15

    It was concluded that reactor the reactor operation is very dangerous for the reactor installation as well as safety of the staff under conditions of heavy water increased activity. Two fundamental arguments in favour of this conclusion are: insufficient possibility of reactor components inspection during maintenance and operation in the future period; difficulties in prevention of accidents that could occur is equally dangerous for the reactor facility and the environment. Cleaning and decontamination of the complete heavy water system is needed before the reactor operation starts in order to avoid possible failures or accidental events. [Serbo-Croat] Zakljuceno je da je eksploatacija reakora u uslovima postojece aktivnosti teskovodnog sistema veoma opasna po sam reaktor i po personal. Dva osnovna razloga u prilog ovog zakljucka su: nedovoljna mogucnost kontrole ispravnosti svih elemenata reaktora u toku remonta i ekspolatacije u predstojecem periodu; teskoca borbe sa udesima, koji bi se eventualno dogodili podjednako je opasna po instalaciju i okolinu. Pre no sto se nastavi sa daljom ekspolatacijom reaktora potrebno ciscenje, dekontaminacija sistema teske vode kako bi se izbegla moguca ostecenja ili akcidentalne situacije.

  13. Research nuclear reactor RA - Annual Report 1994

    International Nuclear Information System (INIS)

    Sotic, O.

    1994-12-01

    Activities related to revitalisation of the RA reactor stared in 1986, were continued in 1991. A number of interventions on the reactor components were finished that are supposed to enable continuous and reliable operation. The last, and at the same time largest action, related to exchange of complete reactor instrumentation is underway, but it is behind the schedule in 1991 because the delivery of components from USSR is late. Production of this instruments is financed by the IAEA according to the contract signed in December 1988 with Russian Atomenergoexport. According to this contract, it has been planned that the RA reactor instrumentation should be delivered to the Vinca Institute by the end of 1990. Only 56% of the instrumentation was delivered until September 1991. Since then any delivery of components to Yugoslavia was stopped because of the temporary embargo imposed by the IAEA. In 1991 most of the existing RA reactor instrumentation was dismantled, only the part needed for basic measurements when reactor is not operated, was maintained. Activities related to improvement of Russian project were continued in 1994. Control and maintenance of the reactor components was done regularly and efficiently. Extensive repair of the secondary coolant loop is almost finished and will be completed in the first part of 1995 according to existing legal procedures and IAEA recommendations. Fuel inspection by the IAEA safeguards inspectors was done on a monthly basis. There have been on the average 47 employees at the RA reactor which is considered sufficient for maintenance and repair conditions. Research reactor RA Annual report for year 1991 is divided into two main parts to cover: (1) operation and maintenance and (2) activities related to radiation protection [sr

  14. A cellular system for quantitation of vitamin K cycle activity: structure-activity effects on vitamin K antagonism by warfarin metabolites

    Science.gov (United States)

    Haque, Jamil A.; McDonald, Matthew G.; Kulman, John D.

    2014-01-01

    Warfarin and other 4-hydroxycoumarins inhibit vitamin K epoxide reductase (VKOR) by depleting reduced vitamin K that is required for posttranslational modification of vitamin K–dependent clotting factors. In vitro prediction of the in vivo potency of vitamin K antagonists is complicated by the complex multicomponent nature of the vitamin K cycle. Here we describe a sensitive assay that enables quantitative analysis of γ-glutamyl carboxylation and its antagonism in live cells. We engineered a human embryonic kidney (HEK) 293–derived cell line (HEK 293-C3) to express a chimeric protein (F9CH) comprising the Gla domain of factor IX fused to the transmembrane and cytoplasmic regions of proline-rich Gla protein 2. Maximal γ-glutamyl carboxylation of F9CH required vitamin K supplementation, and was dose-dependently inhibited by racemic warfarin at a physiologically relevant concentration. Cellular γ-glutamyl carboxylation also exhibited differential VKOR inhibition by warfarin enantiomers (S > R) consistent with their in vivo potencies. We further analyzed the structure-activity relationship for inhibition of γ-glutamyl carboxylation by warfarin metabolites, observing tolerance to phenolic substitution at the C-5 and especially C-6, but not C-7 or C-8, positions on the 4-hydroxycoumarin nucleus. After correction for in vivo concentration and protein binding, 10-hydroxywarfarin and warfarin alcohols were predicted to be the most potent inhibitory metabolites in vivo. PMID:24297869

  15. New acyclic secondary metabolites from the biologically active fraction of Albizia lebbeck flowers.

    Science.gov (United States)

    Al-Massarani, Shaza M; El Gamal, Ali A; Abd El Halim, Mohamed F; Al-Said, Mansour S; Abdel-Kader, Maged S; Basudan, Omer A; Alqasoumi, Saleh I

    2017-01-01

    The total extract of Albizia lebbeck flowers was examined in vivo for its possible hepatoprotective activity in comparison with the standard drug silymarin at two doses. The higher dose expressed promising activity especially in reducing the levels of AST, ALT and bilirubin. Fractionation via liquid-liquid partition and reexamination of the fractions revealed that the n -butanol fraction was the best in improving liver biochemical parameters followed by the n -hexane fraction. However, serum lipid parameters were best improved with CHCl 3 fraction. The promising biological activity results initiated an intensive chromatographic purification of A. lebbeck flowers fractions. Two compounds were identified from natural source for the first time, the acyclic farnesyl sesquiterpene glycoside1-O-[6-O- α -l-arabinopyranosyl- β -d-glucopyranoside]-(2 E ,6 E -)-farnesol ( 6 ) and the squalene derivative 2,3-dihydroxy-2,3-dihydrosqualene ( 9 ), in addition to eight compounds reported here for the first time from the genus Albizia ; two benzyl glycosides, benzyl 1-O- β -d-glucopyranoside ( 1 ) and benzyl 6-O- α -l-arabinopyranosyl β -d-glucopyranoside ( 2 ); three acyclic monoterpene glycosides, linalyl β -d-glucopyranoside ( 3 ) and linalyl 6-O- α -l-arabinopyranosyl- β -d-glucopyranoside ( 4 ); (2 E )-3,7-dimethylocta-2,6-dienoate-6-O- α -l arabinopyranosyl- β -d-glucopyranoside ( 5 ), two oligoglycosides, n -hexyl- α -l arabinopyranosyl-(1 → 6)- β -d-glucopyranoside (creoside) ( 7 ) and n -octyl α -l-arabinopyranosyl-(1 → 6)- β -d-glucopyranoside (rhodiooctanoside) ( 8 ); and ethyl fructofuranoside ( 10 ). The structures of the isolated compounds were elucidated based on extensive examination of their spectroscopic 1D and 2D-NMR, MS, UV, and IR data. It is worth mentioning that, some of the isolated linalol glycoside derivatives were reported as aroma precursors.

  16. New acyclic secondary metabolites from the biologically active fraction of Albizia lebbeck flowers

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    Shaza M. Al-Massarani

    2017-01-01

    Full Text Available The total extract of Albizia lebbeck flowers was examined in vivo for its possible hepatoprotective activity in comparison with the standard drug silymarin at two doses. The higher dose expressed promising activity especially in reducing the levels of AST, ALT and bilirubin. Fractionation via liquid–liquid partition and reexamination of the fractions revealed that the n-butanol fraction was the best in improving liver biochemical parameters followed by the n-hexane fraction. However, serum lipid parameters were best improved with CHCl3 fraction. The promising biological activity results initiated an intensive chromatographic purification of A. lebbeck flowers fractions. Two compounds were identified from natural source for the first time, the acyclic farnesyl sesquiterpene glycoside1-O-[6-O-α-l-arabinopyranosyl-β-d-glucopyranoside]-(2E,6E--farnesol (6 and the squalene derivative 2,3-dihydroxy-2,3-dihydrosqualene (9, in addition to eight compounds reported here for the first time from the genus Albizia; two benzyl glycosides, benzyl 1-O-β-d-glucopyranoside (1 and benzyl 6-O-α-l-arabinopyranosyl β-d-glucopyranoside (2; three acyclic monoterpene glycosides, linalyl β-d-glucopyranoside (3 and linalyl 6-O-α-l-arabinopyranosyl-β-d-glucopyranoside (4; (2E-3,7-dimethylocta-2,6-dienoate-6-O-α-l arabinopyranosyl-β-d-glucopyranoside (5, two oligoglycosides, n-hexyl-α-l arabinopyranosyl-(1 → 6-β-d-glucopyranoside (creoside (7 and n-octyl α-l-arabinopyranosyl-(1 → 6-β-d-glucopyranoside (rhodiooctanoside (8; and ethyl fructofuranoside (10. The structures of the isolated compounds were elucidated based on extensive examination of their spectroscopic 1D and 2D-NMR, MS, UV, and IR data. It is worth mentioning that, some of the isolated linalol glycoside derivatives were reported as aroma precursors.

  17. Secondary Metabolites from Jacaranda Mimosifolia and Kigelia Africana (Bignoniaceae and Their Anticandidal Activity

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    Lazare Sidjui Sidjui

    2014-05-01

    Full Text Available From the stem barks of Jacaranda mimosifolia benzoic acid (1, 1-naphthaleneacetic acid, 5-carboxy- 1,2,3,4,4a,7,8,8a-octahydro-1,2,4a-trimethyl-[1S-(1α,2β,4aβ,8aα] ( 2, betulinic acid ( 3, lupeol (4 and ursolic acid (5 were isolated. Similarly, lapachol (6, dehydro-α-lapachone (7, 2- acetylfuro-1, 4-naphthoquinone (8, p-coumaric acid (9, caffeic acid (10, nonacosanoic acid, 2-(4-hydroxyphenylethyl ester (11, β-sitosterol (12, kigelinol (13, oleanolic acid (14, β-friedelinol (15, pomolic acid (16, and kojic acid (17 were isolated from the stem barks of Kigelia africana. All the isolated compounds were characterized by using spectroscopic methods especially 1D and 2D NMR and ESI mass spectrometry and comparison with literature data. To the best of our knowledge, compounds 1, 2, 3 and 5, and compounds 11, 14, 15 and 16 were isolated for the first time from Jacaranda mimosifolia and Kigelia africana, respectively. All these compounds were screened for anticandidal activity by agar diffusion method and microbroth dilution technique on four Candida albicans strains (ATCCL26, ATCC12C, ATCCP37039, and ATCCP37037. Among them, compounds 9, 10, and 17 exhibited the highest anticandidal activity that varied between the microbial species (MIC= 0.01 ± 0.00 − 0.03 ± 0.00 mg/mL on C. albicans ATCCL26, ATCCP37037, ATCCP37039 and ATCC12C strains. Compound 17 was likely the most active against the four Candida albicans strains (MIC= 0.01 ± 0.00 − 0.02 ± 0.00 mg/mL.

  18. Effect of PCB3 and its hydroxylated metabolites on estradiol secretion, cell viability, and caspase-3 activity in porcine small folicles

    Energy Technology Data Exchange (ETDEWEB)

    Ptak, A.; Gregoraszczuk, E.L. [Lab. of Reproductive Physiology and Toxicology of Domestic Animals, Inst. of Zoology, Jagiellonian Univ., Krakow (Poland); Ludewig, G.; Lehmler, H.J.; Robertson, L.W. [Dept. of Occupational and Environmental Health, Coll. of Public Health, The Univ. of Iowa, Iowa City, IA (United States)

    2004-09-15

    In general, highly chlorinated PCBs are slowly metabolized and eliminated. Lower chlorinated PCBs on the other hand are hydroxylated in vitro and in vivo. Surprisingly this does not necessarily mean that these hydroxylated PCBs are rapidly excreted, as recent findings of substantial amounts of hydroxylated PCBs in animal and human blood have shown. Therefore it must be assumed that not only the PCBs themselves, but also their metabolites can participate in the toxic effects of PCBs. Indeed, some hydroxylated metabolites of PCBs (OH-PCBs) have significant estrogenic activity through binding to the estrogen receptors. Surprisingly, PCB54 (2,2',6,6'-tetrachlorobiphenyl) has about 10% of the activity of 4-OH-PCB54 in the MCF-7 focus assay, but does not bind to the estrogen receptor, suggesting the possibility of an additional, yet unknown mechanism of estrogenicity. We found that PCBs and their hydroxylated metabolites cause an increase in estrogen secretion from ovarian follicular cells in vitro, with PCB3 < 4-OHPCB3 < 3, 4-OH-PCB3. The most sensitive follicles were those collected during the early stage of their development. In the present study we used this type of follicles to answer the question whether this observed huge stimulatory action of PCB3 and/or its metabolites on estrogen release into the medium is due to the action on cells viability and cell apoptosis.

  19. Three New and Eleven Known Unusual C25 Steroids: Activated Production of Silent Metabolites in a Marine-Derived Fungus by Chemical Mutagenesis Strategy using Diethyl Sulphate

    Directory of Open Access Journals (Sweden)

    Ming-Wen Xia

    2014-03-01

    Full Text Available Three new (1–3 and 11 known (4–14 C25 steroids with an unusual bicyclo[4.4.1]A/B ring system were isolated by tracing newly produced metabolites in the EtOAc extract of an antitumor mutant AD-1-2 obtained by the diethyl sulphate (DES mutagenesis of a marine-derived Penicillium purpurogenum G59. HPLC-PDAD-UV and HPLC-ESI-MS analyses indicated that the G59 strain did not produce these metabolites and the production of 1–14 in the mutant AD-1-2 extract was caused by the activation of silent metabolites in the original G59 strain by DES mutagenesis. The structures of the new compounds, named antineocyclocitrinols A (1 and B (2 and 23-O-methylantineocyclocitrinol (3, including their absolute configurations were determined by various spectroscopic methods, especially the NMR and Mo2-induced CD analyses. Compounds 1–3 provide the first examples of the C25 bicyclo[4.4.1]A/B ring steroids with the Z-configuration of 20,22-double bond. All of 1–14 weakly inhibited several human cancer cell lines to varying extents. These results provided additional examples for the successful application of the chemical mutagenesis strategy using DES to discover new compounds by activating silent metabolites in fungal isolates and supported also the effectiveness and usefulness of this new strategy.

  20. Secondary Metabolite Profile, Antioxidant Capacity, and Mosquito Repellent Activity of Bixa orellana from Brazilian Amazon Region

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    Annamaria Giorgi

    2013-01-01

    Full Text Available The Brazilian flora was widely used as source of food and natural remedies to treat various diseases. Bixa orellana L. (Bixaceae, also known as annatto, urucù, or achiote, is a symbol for the Amazonian tribes that traditionally use its seeds as coloured ink to paint their bodies for religious ceremonies. The aim of this study was to investigate the volatile organic compounds (VOCs profile of B. orellana fresh fruits (in vivo sampled, dried seeds, wood, bark, and leaves analyzed with Headspace solid-phase microextraction coupled with gas chromatography and mass spectrometry. A screening on phenolic content (the Folin-Ciocalteu assay and antiradical activity (DPPH assay of seeds was also conducted. In addition, the repellent properties of seed extracts against Aedes aegypti L. were investigated. Volatile compounds detected in B. orellana samples consisted mainly of sesquiterpenes, monoterpenes, and arenes: α-humulene is the major volatile compound present in seed extracts followed by D-germacrene, γ-elemene, and caryophyllene. B. orellana proved to be a good source of antioxidants. Preliminary data on repellency against A. aegypti of three different dried seed extracts (hexane, ethanol, and ethanol/water indicated a significant skin protection activity. A protection of 90% and 73% for hexane and ethanol/water extracts was recorded.

  1. Secondary metabolites of ponderosa lemon (Citrus pyriformis) and their antioxidant, anti-inflammatory, and cytotoxic activities.

    Science.gov (United States)

    Hamdan, Dalia; El-Readi, Mahmoud Zaki; Tahrani, Ahmad; Herrmann, Florian; Kaufmann, Dorothea; Farrag, Nawal; El-Shazly, Assem; Wink, Michael

    2011-01-01

    Column chromatography of the dichloromethane fraction from an aqueous methanolic extract of fruit peel of Citrus pyriformis Hassk. (Rutaceae) resulted in the isolation of seven compounds including one coumarin (citropten), two limonoids (limonin and deacetylnomilin), and four sterols (stigmasterol, ergosterol, sitosteryl-3-beta-D-glucoside, and sitosteryl-6'-O-acyl-3-beta-D-glucoside). From the ethyl acetate fraction naringin, hesperidin, and neohesperidin were isolated. The dichloromethane extract of the defatted seeds contained three additional compounds, nomilin, ichangin, and cholesterol. The isolated compounds were identified by MS (EI, CI, and ESI), 1H, 13C, and 2D-NMR spectral data. The limonoids were determined qualitatively by LC-ESI/MS resulting in the identification of 11 limonoid aglycones. The total methanolic extract of the peel and the petroleum ether, dichloromethane, and ethyl acetate fractions were screened for their antioxidant and anti-inflammatory activities. The ethyl acetate fraction exhibited a significant scavenging activity for DPPH free radicals (IC50 = 132.3 microg/mL). The petroleum ether fraction inhibited 5-lipoxygenase with IC50 = 30.6 microg/mL indicating potential anti-inflammatory properties. Limonin has a potent cytotoxic effect against COS7 cells [IC50 = (35.0 +/- 6.1) microM] compared with acteoside as a positive control [IC50 = (144.5 +/- 10.96) microM].

  2. Serum nitric oxide metabolites and disease activity in patients with systemic sclerosis.

    Science.gov (United States)

    Mok, Mo Yin; Fung, Peter Chin Wah; Ooi, Clara; Tse, Hung Fat; Wong, Yik; Lam, Yui Ming; Wong, Woon Sing; Lau, Chak Sing

    2008-03-01

    There is no surrogate marker in serum for defining disease activity in scleroderma (SSc). Nitric oxide (NO), which regulates vasodilation and possesses pro-inflammatory actions, has been implicated in the pathogenesis of SSc. We compared serum NO(x) (total nitrate and nitrite) level in SSc patients to healthy controls and evaluated its correlation with detailed symptomatology and scoring systems for various organ involvement. Symptoms and physical findings that suggested disease activity in regard to various organs were documented. Lung function test, high-resolution computed tomographic (HRCT) scan of thorax and echocardiography were performed. Serum NO(x) was measured by chemiluminescence. Serum NO(x) levels in SSc (n = 43) were significantly higher (72.4 +/- 47.8 microM) than age- and sex-matched controls (n = 41; 37.1 +/- 13.5 microM; p n = 9; OR 145.3, p = 0.01) were predictive factors for elevated serum NO(x). Prednisolone use was associated with lower serum NO(x) level (OR 0.06, p = 0.04). Elevated PAP of increasing severity was found to be associated with higher level of serum NO(x) (p = 0.004 by trend). Serum NO(x) in SSc patients were elevated compared to healthy controls. Serum NO(x) level was determined by multiple factors including age, prednisolone use, and elevated PAP.

  3. Identification of metabolites involved in the biodegradation of the ionic liquid 1-butyl-3-methylpyridinium bromide by activated sludge microorganisms.

    Science.gov (United States)

    Pham, Thi Phuong Thuy; Cho, Chul-Woong; Jeon, Che-Ok; Chung, Yun-Jo; Lee, Min-Woo; Yun, Yeoung-Sang

    2009-01-15

    Ionic liquids (ILs) are low melting organic salts that potentially comprise wide application due to their fascinating properties and have emerged as promising "green" replacements for volatile organic solvents. Despite their nonmeasurable vapor pressure, some quantities of ILs will soon be present in effluent discharges since they do have significant solubility in water. Recently, the toxic effects of ILs toward aquatic communities have been intensively investigated, but little information is available concerning the biodegradable properties of these compounds. The objective of this study was to identify the metabolites generated during the biotransformation of 1-butyl-3-methylpyridinium by microorganisms in aerobic activated sludge. The obtained results revealed that the alkylpyridinium salt was metabolized through the sequential oxidization in different positions of the alkyl side chains. High-performance liquid chromatography and mass-spectrometry analyses demonstrated that this biodegradation led to the formation of 1-hydroxybutyl-3-methylpyridinium, 1-(2-hydroxybutal)-3-methylpyridinium, 1-(2-hydroxyethyl)-3-methylpyridinium, and methylpyridine. On the basis of these intermediate products, biodegradation pathways were also suggested. These findings provide the basic information that might be useful for assessing the factors related to the environmental fate and behavior of this commonly used pyridinium IL.

  4. Limited-sampling strategy models for estimating the pharmacokinetic parameters of 4-methylaminoantipyrine, an active metabolite of dipyrone

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    Suarez-Kurtz G.

    2001-01-01

    Full Text Available Bioanalytical data from a bioequivalence study were used to develop limited-sampling strategy (LSS models for estimating the area under the plasma concentration versus time curve (AUC and the peak plasma concentration (Cmax of 4-methylaminoantipyrine (MAA, an active metabolite of dipyrone. Twelve healthy adult male volunteers received single 600 mg oral doses of dipyrone in two formulations at a 7-day interval in a randomized, crossover protocol. Plasma concentrations of MAA (N = 336, measured by HPLC, were used to develop LSS models. Linear regression analysis and a "jack-knife" validation procedure revealed that the AUC0-¥ and the Cmax of MAA can be accurately predicted (R²>0.95, bias 0.85 of the AUC0-¥ or Cmax for the other formulation. LSS models based on three sampling points (1.5, 4 and 24 h, but using different coefficients for AUC0-¥ and Cmax, predicted the individual values of both parameters for the enrolled volunteers (R²>0.88, bias = -0.65 and -0.37%, precision = 4.3 and 7.4% as well as for plasma concentration data sets generated by simulation (R²>0.88, bias = -1.9 and 8.5%, precision = 5.2 and 8.7%. Bioequivalence assessment of the dipyrone formulations based on the 90% confidence interval of log-transformed AUC0-¥ and Cmax provided similar results when either the best-estimated or the LSS-derived metrics were used.

  5. Effects of extremely low frequency electromagnetic fields on paraoxonase serum activity and lipid peroxidation metabolites in rat.

    Science.gov (United States)

    Seifirad, Soroush; Farzampour, Shahrokh; Nourbakhsh, Mitra; Amoli, Mahsa Mohammad; Razzaghy-Azar, Maryam; Larijani, Bagher

    2014-01-01

    Atherogenic effects of ELF-MF exposure have not been studied well so far. Therefore we have hypothesized that ELF-MF exposure might have atherogenic effect by impairing antioxidant function and increasing lipid peroxidation. This study was therefore undertaken to examine the effects of ELF-MF on paraoxonase (PON) activity, antioxidant capacity and lipid peroxidation metabolites. Effects of time on remodeling of antioxidant system were also investigated in this study. Seventy five Wistar rats were randomly allocated into five groups as follows: 1) Sham exposure, 2) Single exposure to 60 Hz, sacrificed immediately after exposure, 3) Single exposure to 60 Hz, sacrificed 72 hours after exposure, 4) Fourteen days of exposure to 60 Hz, sacrificed immediately after exposure, and 5) Fourteen days of exposure to 60 Hz, sacrificed 72 hours after exposure. Blood samples were collected and analyzed. The results were compared using ANOVA and post hoc Tukey HSD for multiple caparisons. Single ELF-MF exposure significantly increased lipid peroxidation (CD and MDA) and increased antioxidant serum activity (HDL, paraoxonase activity, and serum total antioxidant capacity). Chronic ELF-MF exposure increased lipid peroxidation and affected antioxidant system. Free fatty acids levels were significantly increased after both single and two weeks exposure. Chronic exposure led to irreversible changes while acute exposure tended to reversible alterations on above mentioned parameters. According to the results of this study, ELF-MF exposure could impair oxidant-antioxidant function and might increase oxidative stress and lipid peroxidation. Antioxidant capability was dependent on the duration and continuity of ELF-MF exposure.

  6. Secondary Metabolites from Two Species of Tolpis and Their Biological Activities

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    Francisco León

    2012-11-01

    Full Text Available Phytochemical research of two Tolpis species, T. proustii and T. lagopoda, led to the isolation of three new compounds: 30-chloro-3β-acetoxy-22α-hydroxyl-20(21-taraxastene (1, 3β,22α-diacetoxy-30-ethoxy-20(21-taraxastene (2 and 3β,28-dihydroxy-11α-hydroperoxy-12-ursene (3. The structures of the new compounds were elucidated by means of extensive IR, NMR, and MS data and by comparison of data reported in the literature. The in vitro antioxidant activities of the extracts were assessed by the DPPH and ABTS scavenging methods. The cytotoxicity of several known compounds and its derivatives was also assessed against human myeloid leukemia K-562 and K-562/ADR cell lines.

  7. First secondary metabolites from Herissantia crispa L (Brizicky) and the toxicity activity against Artemia salina Leach

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Danielly Albuquerque da; Matias, Wemerson Neves; Lima, Igara Oliveira; Xavier, Aline Lira; Costa, Vivian Bruna Machado; Diniz, Margareth de Fatima Formiga Melo; Agra, Maria de Fatima; Batista, Leonia Maria; Souza, Maria de Fatima Vanderlei de [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Lab. de Tecnologia Farmaceutica Prof. Delby Fernandes de Medeiros; Silva, Davi Antas e [Universidade Federal Rural de Pernambuco, Serra Talhada, PE (Brazil). Dept. de Quimica

    2009-07-01

    The phytochemical investigation of Herissantia crispa led to the isolation of seven compounds, identified as: sitosterol 3-O-{beta}-D-glucopyranoside, stigmasterol 3-O-{beta}-D-glucopyranoside, 3,5,7,4'-tetrahydroxyflavone (kaempferol), 3,5,7,3',4'-pentahydroxyflavone (quercetin), unpublished in the genus Herissantia, besides {beta}-sitosterol, kaempferol 3-O-{beta}-D-(6''-E-p-coumaroil) (tiliroside) glucopyranoside and kaempferol 3,7-di-O-{alpha}-L-ramnopyranoside (lespedin), described for the first time in the species. The structural determination of the compounds was made by means of spectroscopy methods such as Infrared Spectroscopy, {sup 1}H and {sup 13}C Nuclear Magnetic Resonance, with the aid of two dimensional techniques, and by comparison with literature data. The toxicity activity of the MeOH extract and lespedin on Artemia salina Leach. was also carried out. (author)

  8. First secondary metabolites from Herissantia crispa L (Brizicky) and the toxicity activity against Artemia salina Leach

    International Nuclear Information System (INIS)

    Costa, Danielly Albuquerque da; Matias, Wemerson Neves; Lima, Igara Oliveira; Xavier, Aline Lira; Costa, Vivian Bruna Machado; Diniz, Margareth de Fatima Formiga Melo; Agra, Maria de Fatima; Batista, Leonia Maria; Souza, Maria de Fatima Vanderlei de; Silva, Davi Antas e

    2009-01-01

    The phytochemical investigation of Herissantia crispa led to the isolation of seven compounds, identified as: sitosterol 3-O-β-D-glucopyranoside, stigmasterol 3-O-β-D-glucopyranoside, 3,5,7,4'-tetrahydroxyflavone (kaempferol), 3,5,7,3',4'-pentahydroxyflavone (quercetin), unpublished in the genus Herissantia, besides β-sitosterol, kaempferol 3-O-β-D-(6''-E-p-coumaroil) (tiliroside) glucopyranoside and kaempferol 3,7-di-O-α-L-ramnopyranoside (lespedin), described for the first time in the species. The structural determination of the compounds was made by means of spectroscopy methods such as Infrared Spectroscopy, 1 H and 13 C Nuclear Magnetic Resonance, with the aid of two dimensional techniques, and by comparison with literature data. The toxicity activity of the MeOH extract and lespedin on Artemia salina Leach. was also carried out. (author)

  9. Vitamin A active metabolite, all-trans retinoic acid, induces spinal cord sensitization. II. Effects after intrathecal administration

    Science.gov (United States)

    Alique, M; Lucio, F J; Herrero, J F

    2006-01-01

    Background and purpose: In our previous study (see accompanying paper) we observed that all-trans retinoic acid (ATRA) p.o. induces changes in spinal cord neuronal responses similar to those observed in inflammation-induced sensitization. In the present study we assessed the it. effects of ATRA, and its mechanisms of action. Experimental approach: The effects of all drugs were studied after it. administration in nociceptive withdrawal reflexes using behavioural tests in awake male Wistar rats. Key results: The administration of ATRA in normal rats induced a dose-dependent enhancement of nociceptive responses to noxious mechanical and thermal stimulation, as well as responses to innocuous stimulation. The intensity of the responses was similar to that observed in non-treated animals after carrageenan-induced inflammation. The effect induced by ATRA was fully prevented by the previous administration of the retinoic acid receptor (RAR) pan-antagonist LE540 but not by the retinoid X receptor (RXR) pan-antagonist HX531, suggesting a selective action on spinal cord RARs. The COX inhibitor dexketoprofen and the interleukin-1 receptor antagonist IL-1ra inhibited ATRA effect. The results indicate that COX and interleukin-1 are involved in the effects of ATRA in the spinal cord, similar to that seen in inflammation. Conclusions and implications: In conclusion, ATRA induces changes in the spinal cord similar to those observed in inflammation. The sensitization-like effect induced by ATRA was mediated by RARs and associated with a modulation of COX-2 and interleukin-1 activities. ATRA might be involved in the mechanisms underlying the initiation and/or maintenance of sensitization in the spinal cord. PMID:16847438

  10. Preliminary Study and Improve the Production of Metabolites with Antifungal Activity by A Bacillus Sp Strain IBA 33

    Directory of Open Access Journals (Sweden)

    María Antonieta Gordillo

    2009-01-01

    Full Text Available Bacillus sp strain IBA 33 metabolites, isolated from decaying lemon fruits, were evaluated for the control of pathogenic and non-pathogenic fungi (Penicillium digitatum, Geotrichum candidum, Penicillium expansum, Aspergillus clavatus, Aspergillus flavus, Aspergillus niger, and Fusarium moniliforme. These metabolites were recovered from Landy medium (LM without aminoacids. In order to optimize metabolites production the LM was modified by adding different concentrations and sources of amino acids and carbohydrates at different culture conditions.Bacillus sp strain IBA 33 metabolites efficacy to control fungi were evaluated with in vitro and in vivo assays. A. flavus growth inhibition was 52% with the metabolites of Bacillus sp strain IBA 33 recovered from LM (MBLM in vitro assays. MBLM supplemented with 0.5% glutamic acid, inhibited the growth of P. digitatum, G. candidum, A. clavatus, A. niger and F. moniliforme by 65%, 88.44%, 84%, 34% and 92% respectively. The highest inhibition of P. expansum was 45% with MBLM supplemented with 0.5% aspartic acid. Similar results were obtained in vivo assays. These results showed that Bacillus sp strain IBA 33 metabolites specificity against fungi depended on the composition of the LM.

  11. Preliminary Study and Improve the Production of Metabolites with Antifungal Activity by A Bacillus Sp Strain IBA 33

    Directory of Open Access Journals (Sweden)

    María Antonieta Gordillo

    2009-04-01

    Full Text Available Bacillus sp strain IBA 33 metabolites, isolated from decaying lemon fruits, were evaluated for the control of pathogenic and non-pathogenic fungi (Penicillium digitatum, Geotrichum candidum, Penicillium expansum, Aspergillus clavatus, Aspergillus flavus, Aspergillus niger, and Fusarium moniliforme. These metabolites were recovered from Landy medium (LM without aminoacids. In order to optimize metabolites production the LM was modified by adding different concentrations and sources of amino acids and carbohydrates at different culture conditions. Bacillus sp strain IBA 33 metabolites efficacy to control fungi were evaluated with in vitro and in vivo assays. A. flavus growth inhibition was 52% with the metabolites of Bacillus sp strain IBA 33 recovered from LM (MBLM in vitro assays. MBLM supplemented with 0.5% glutamic acid, inhibited the growth of P. digitatum, G. candidum, A. clavatus, A. niger and F. moniliforme by 65%, 88.44%, 84%, 34% and 92% respectively. The highest inhibition of P. expansum was 45% with MBLM supplemented with 0.5% aspartic acid. Similar results were obtained in vivo assays. These results showed that Bacillus sp strain IBA 33 metabolites specificity against fungi depended on the composition of the LM.

  12. Phase I hydroxylated metabolites of the K2 synthetic cannabinoid JWH-018 retain in vitro and in vivo cannabinoid 1 receptor affinity and activity.

    Directory of Open Access Journals (Sweden)

    Lisa K Brents

    Full Text Available K2 products are synthetic cannabinoid-laced, marijuana-like drugs of abuse, use of which is often associated with clinical symptoms atypical of marijuana use, including hypertension, agitation, hallucinations, psychosis, seizures and panic attacks. JWH-018, a prevalent K2 synthetic cannabinoid, is structurally distinct from Δ(9-THC, the main psychoactive ingredient in marijuana. Since even subtle structural differences can lead to differential metabolism, formation of novel, biologically active metabolites may be responsible for the distinct effects associated with K2 use. The present study proposes that K2's high adverse effect occurrence is due, at least in part, to distinct JWH-018 metabolite activity at the cannabinoid 1 receptor (CB1R.JWH-018, five potential monohydroxylated metabolites (M1-M5, and one carboxy metabolite (M6 were examined in mouse brain homogenates containing CB1Rs, first for CB1R affinity using a competition binding assay employing the cannabinoid receptor radioligand [(3H]CP-55,940, and then for CB1R intrinsic efficacy using an [(35S]GTPγS binding assay. JWH-018 and M1-M5 bound CB1Rs with high affinity, exhibiting K(i values that were lower than or equivalent to Δ(9-THC. These molecules also stimulated G-proteins with equal or greater efficacy relative to Δ(9-THC, a CB1R partial agonist. Most importantly, JWH-018, M2, M3, and M5 produced full CB1R agonist levels of activation. CB1R-mediated activation was demonstrated by blockade with O-2050, a CB1R-selective neutral antagonist. Similar to Δ(9-THC, JWH-018 and M1 produced a marked depression of locomotor activity and core body temperature in mice that were both blocked by the CB1R-preferring antagonist/inverse agonist AM251.Unlike metabolites of most drugs, the studied JWH-018 monohydroxylated compounds, but not the carboxy metabolite, retain in vitro and in vivo activity at CB1Rs. These observations, combined with higher CB1R affinity and activity relative to Δ(9

  13. Research nuclear reactor RA - Annual Report 1997; Istrazivacki nuklearni reaktor RA - Izvestaj za 1997. godinu

    Energy Technology Data Exchange (ETDEWEB)

    Sotic, O [Vinca Institute of Nuclear Sciences, Beograd (Serbia and Montenegro)

    1997-12-01

    RA reactor is not in operation since 1984, activities related to revitalisation of the RA reactor started in 1986. The planned actions related to renewal of the reactor components were finished except for the most important action, related to exchange of complete reactor instrumentation which was delayed. Only 80% of the instrumentation was delivered until September 1991. Since then any delivery of components to Yugoslavia was stopped because of the sanctions imposed to our country. The existing RA reactor instrumentation was dismantled. Control and maintenance of the reactor components was done regularly and efficiently. Fuel inspection by the IAEA safeguards inspectors was done on a monthly basis. There have been on the average 42 employees at the RA reactor which is considered sufficient for maintenance and repair conditions. The problem of financing the reactor activities and maintenance remains unsolved. Research reactor RA Annual report for year 1997 is divided into two main parts to cover: (1) operation and maintenance and (2) activities related to radiation protection. [Serbo-Croat] Reaktor RA nije u pogonu od 1984, aktivnosti na revitalizaciji, rekostrukciji i modernizaciji reaktorski sistema zapocete su 1986. godine. Okoncan je niz zahvata na opremi postrojenja kojima ce se u narednom periodu omoguciti kontinualan i pouzdan rad ovog reaktora. Poslednji, i ujedno najveci zahvat, koji se odnosi na zamenu celokupne instrumentacije kasni zbog zastoja u isporuci opreme koja se izradjuje u Sovjetskom savezu. Do septembra 1991. godine isporuceno svega 80% od predvidjene kolicine. Od tada je svaka isporuka obustavljena, a razlog je privremena zabrana na sve isporuke opreme za Jugoslaviju usled sankcija uvedenih od strane organizacije Ujedinjenih nacija. Demontirana je postojeca instrumentacija. Kontrola i odrzavanje celopkupne opreme postrojenja, kao i remontni radovi izvrsavani su redovno i efikasno. Kontrola goriva od strane safeguard inspektora MAAE obavljana

  14. Impact of a magnetic resonance imaging-guided treat-to-target strategy on disease activity and progression in patients with rheumatoid arthritis (the IMAGINE-RA trial)

    DEFF Research Database (Denmark)

    Møller-Bisgaard, Signe; Hørslev-Petersen, Kim; Ejbjerg, Bo Jannik

    2015-01-01

    /absence of BME may therefore be clinically beneficial. We present the design of a randomized controlled trial (RCT) aiming to evaluate whether an MRI-guided treatment strategy compared to a conventional treatment strategy in anti-CCP-positive erosive RA is better to prevent progression of erosive joint damage...... swollen joints and treatment with synthetic disease-modifying antirheumatic drugs (DMARDs) will be included. Patients will be randomized to either a treatment strategy based on conventional laboratory and clinical examinations (control group) or a treatment strategy based on conventional laboratory...

  15. Lipid metabolites with free-radical scavenging activity from Euphorbia helioscopia L.

    Science.gov (United States)

    Cateni, F; Zilic, J; Altieri, T; Zacchigna, M; Procida, G; Gaggeri, R; Rossi, D; Collina, S

    2014-07-01

    The methanolic extract of the plant Euphorbia helioscopia L. exhibited an interesting free-radical scavenging activity. From the aerial parts of Euphorbia helioscopia L. (Euphorbiaceae), a complex mixture of seven cerebrosides together with glucoclionasterol, a digalactosyldiacylglycerol and a diacylmonogalactosylglycerol were identified. The structures of the cerebrosides were characterized as 1-O-β-D-glucosides of phytosphingosines, which comprised (2S, 3S, 4E, 8E)-2-amino-4(E),8(E)-octadecadiene-1,3-diol, (2S, 3S, 4E, 8Z)-2-amino-4(E),8(Z)-octadecadiene-1,3-diol, (2S, 3S, 4R, 8Z)-2-amino-8(Z)-octadecene-1,3,4-triol as long chain bases with seven 2-hydroxy fatty acids of varying chain lengths (C16, C24:1, C26:1, C24, C26, C28:1) linked to the amino group. The glycosylglycerides were characterized as (2S)-2,3-O-di-(9,12,15-octadecatrienoyl)-glyceryl-6-O-(α-D-galactopyranosyl)-β-D-galactopyranoside and (2S)-2,3-O-di-(9,12,15-octadecatrienoyl)-glyceryl-1-O-β-D-galactopyranoside. The structures were established on the basis of spectroscopic data and chemical reactions. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Evaluation of wound healing activity of atranorin, a lichen secondary metabolite, on rodents

    Directory of Open Access Journals (Sweden)

    Rosana S. S. Barreto

    2013-02-01

    Full Text Available The aim of this study was to investigate the wound healing activity of atranorin cream (Patent requested on excision wounds. Seventy-two male rats were anesthetized and an excisional wound was performed. Then the rats were randomly assigned into three groups: untreated control group; atranorin 1 (group treated with 1% AT ointment; and atranorin 5 (group treated with 5% AT ointment. Six animals of each group were euthanized 3, 7, 14 or 21 days after surgical procedures and the wounded areas were analyzed and removed. Serial histological sections were obtained and stained by histochemical techniques (Hematoxilin-Eosin-HEand Sirius red and immunohistochemical techniques. Topical application of atranorin reduced wound areas, induced earlier granulation tissue formation, increased cell proliferation, improved collagenization and modulated the myofibroblasts differentiation when compared to control animals. It is suggested that atranorin modulates the wound healing process. These data suggest that this formulation based on atranorin extracted from Cladina kalbii AHTI may be a new biotechnological product for wound healing clinical applications.

  17. Antifungal activity against plant pathogens of metabolites from the endophytic fungus Cladosporium cladosporioides.

    Science.gov (United States)

    Wang, Xiaoning; Radwan, Mohamed M; Taráwneh, Amer H; Gao, Jiangtao; Wedge, David E; Rosa, Luiz H; Cutler, Horace G; Cutler, Stephen J

    2013-05-15

    Bioassay-guided fractionation of Cladosporium cladosporioides (Fresen.) de Vries extracts led to the isolation of four compounds, including cladosporin, 1; isocladosporin, 2; 5'-hydroxyasperentin, 3; and cladosporin-8-methyl ether, 4. An additional compound, 5',6-diacetylcladosporin, 5, was synthesized by acetylation of compound 3. Compounds 1-5 were evaluated for antifungal activity against plant pathogens. Phomopsis viticola was the most sensitive fungus to the tested compounds. At 30 μM, compound 1 exhibited 92.7, 90.1, 95.4, and 79.9% growth inhibition against Colletotrichum acutatum , Colletotrichum fragariae , Colletotrichum gloeosporioides , and P. viticola, respectively. Compound 2 showed 50.4, 60.2, and 83.0% growth inhibition at 30 μM against Co. fragariae, Co. gloeosporioides, and P. viticola, respectively. Compounds 3 and 4 were isolated for the first time from Cl. cladosporioides. Moreover, the identification of essential structural features of the cladosporin nuclei has also been evaluated. These structures provide new templates for the potential treatment and management of plant diseases.

  18. Effect of Supercritical Carbon Dioxide Extraction Parameters on the Biological Activities and Metabolites Present in Extracts from Arthrospira platensis.

    Science.gov (United States)

    Esquivel-Hernández, Diego A; Rodríguez-Rodríguez, José; Cuéllar-Bermúdez, Sara P; García-Pérez, J Saúl; Mancera-Andrade, Elena I; Núñez-Echevarría, Jade E; Ontiveros-Valencia, Aura; Rostro-Alanis, Magdalena; García-García, Rebeca M; Torres, J Antonio; Chen, Wei Ning; Parra-Saldívar, Roberto

    2017-06-12

    Arthrospira platensis was used to obtain functional extracts through supercritical carbon dioxide extraction (SFE-CO₂). Pressure (P), temperature (T), co-solvent (CX), static extraction (SX), dispersant (Di) and dynamic extraction (DX) were evaluated as process parameters through a Plackett-Burman design. The maximum extract yield obtained was 7.48 ± 0.15% w/w. The maximum contents of bioactive metabolites in extracts were 0.69 ± 0.09 µg/g of riboflavin, 5.49 ± 0.10 µg/g of α-tocopherol, 524.46 ± 0.10 µg/g of β-carotene, 1.44 ± 0.10 µg/g of lutein and 32.11 ± 0.12 mg/g of fatty acids with 39.38% of palmitic acid, 20.63% of linoleic acid and 30.27% of γ-linolenic acid. A. platensis extracts had an antioxidant activity of 76.47 ± 0.71 µg GAE/g by Folin-Ciocalteu assay, 0.52 ± 0.02, 0.40 ± 0.01 and 1.47 ± 0.02 µmol TE/g by DPPH, FRAP and TEAC assays, respectively. These extracts showed antimicrobial activity against Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922 and Candida albicans ATCC 10231. Overall, co-solvent was the most significant factor for all measured effects ( p extraction parameters P: 450 bar, CX: 11 g/min, SX: 15 min, DX: 25 min, T: 60 °C and Di: 35 g.

  19. THE IMMUNOLOGICAL CHARACTERISTIC OF RA PATIENTS WITH ANAEMIA

    Directory of Open Access Journals (Sweden)

    A. E. Sizikov

    2014-07-01

    Full Text Available Abstract. The aim of the investigation was to study the immunological characteristics of RA patients with anaemia. Clinical and laboratory data including the percentage of the main lymphocyte subclasses, phagocyte and DTH-effector activity, serum concentration of immunoglobulins, the percentage of cells producing IFNγ and/or IL-4 and percent of monocytes producing TNF. We revealed some significant clinical, laboratory and immunological differences between RA patients and healthy donors and between patients with and without anaemia. Our data demonstrate RA anemic patients to have more severe disorders than patients without anaemia. We also revealed some significant immunological differences between RA patients and healthy donors and between patients with and without anaemia, including percent of cells producing IFNγ and/or IL-4. Our data permit to conclude that RA patients have many different immunological disturbances, more severe in anaemic patients.

  20. Secondary metabolites from Ganoderma.

    Science.gov (United States)

    Baby, Sabulal; Johnson, Anil John; Govindan, Balaji

    2015-06-01

    Ganoderma is a genus of medicinal mushrooms. This review deals with secondary metabolites isolated from Ganoderma and their biological significance. Phytochemical studies over the last 40years led to the isolation of 431 secondary metabolites from various Ganoderma species. The major secondary compounds isolated are (a) C30 lanostanes (ganoderic acids), (b) C30 lanostanes (aldehydes, alcohols, esters, glycosides, lactones, ketones), (c) C27 lanostanes (lucidenic acids), (d) C27 lanostanes (alcohols, lactones, esters), (e) C24, C25 lanostanes (f) C30 pentacyclic triterpenes, (g) meroterpenoids, (h) farnesyl hydroquinones (meroterpenoids), (i) C15 sesquiterpenoids, (j) steroids, (k) alkaloids, (l) prenyl hydroquinone (m) benzofurans, (n) benzopyran-4-one derivatives and (o) benzenoid derivatives. Ganoderma lucidum is the species extensively studied for its secondary metabolites and biological activities. Ganoderma applanatum, Ganoderma colossum, Ganoderma sinense, Ganoderma cochlear, Ganoderma tsugae, Ganoderma amboinense, Ganoderma orbiforme, Ganoderma resinaceum, Ganoderma hainanense, Ganoderma concinna, Ganoderma pfeifferi, Ganoderma neo-japonicum, Ganoderma tropicum, Ganoderma australe, Ganoderma carnosum, Ganoderma fornicatum, Ganoderma lipsiense (synonym G. applanatum), Ganoderma mastoporum, Ganoderma theaecolum, Ganoderma boninense, Ganoderma capense and Ganoderma annulare are the other Ganoderma species subjected to phytochemical studies. Further phytochemical studies on Ganoderma could lead to the discovery of hitherto unknown biologically active secondary metabolites. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Operators retraining in RA-1

    International Nuclear Information System (INIS)

    Pereira, R; Daoud, A

    2012-01-01

    The nuclear activity in Argentina has its foundational milestone in the creation of the Comision Nacional de EnergIa Atomica in 1950. Achievements since then, linked to the area of nuclear reactors and nuclear fuel materials, fuel cycle facilities and the applications of nuclear technology in medicine, industry, agriculture, food preservation, environmental studies and many others, have relied on personnel trained in this specific technology in both professional and technical level. This training has been done in most cases in the exclusive scope of CNEA. Eventually CNEA has been linked with the University to ensure that personnel training concerned to work done in the nuclear field had guarantees of formality and excellence. The creation of the Instituto de Tecnologia Nuclear Dan Beninson that, under an agreement with the Universidad Nacional de General San Martin, has set up an enabling environment for the training of professionals and university technicians to serve with the multiple and growing use of this technology. On the other hand the Institute has been issuing, along with its careers, specialized courses that, in some cases, have been requested by CNEA's nuclear installations and companies related to the nuclear sector. In particular, the Specialization in Nuclear Reactors and its Fuel Cycle (ERCC) and the Courses of Introduction to Nuclear Technology-Complementary training for Installations Personnel Class I (CI-CC), this last, recognized by the ARN as a requirement for applying to the individual licensing examination, providing work experience in the RA-1 reactor among which we can find commissioning, control rods calibration by various methods and calculations of reactivity. With this practical framework developed in the RA-1 and the academic support provided by the Instituto de Tecnologia Nuclear Dan Beninson it was developed a training program for nuclear reactors operators. Let us stress that this research reactor has been forming generations

  2. In vitro activity of solithromycin and its metabolites, CEM-214 and N-acetyl-CEM-101, against 100 clinical Ureaplasma spp. isolates compared with azithromycin.

    Science.gov (United States)

    Furfaro, Lucy L; Spiller, O Brad; Keelan, Jeffrey A; Payne, Matthew S

    2015-09-01

    There is a strong association between vaginal and/or amniotic fluid Ureaplasma spp. colonisation and risk of preterm birth. The novel fluoroketolide antibiotic solithromycin (CEM-101) is active against Ureaplasma spp. in vitro. Evidence from ex vivo and in vivo models suggests that, unlike most macrolide antibiotics, solithromycin readily crosses the placenta. Solithromycin metabolism varies according to species; in pregnant sheep, the bioactive metabolites CEM-214 and N-acetyl-CEM-101 (NAc-CEM-101) have been shown to accumulate in the amniotic cavity following maternal solithromycin administration, potentially contributing to its antimicrobial effects. To determine the antimicrobial activity of these metabolites against Ureaplasma spp., the effects of solithromycin, CEM-214, NAc-CEM-101 and the comparator azithromycin were tested on a collection of 100 clinical Ureaplasma spp. isolates from the UK and Australia using a modified 96-well broth microdilution method. MIC90 values observed for the combined cohort were: solithromycin, 0.125 mg/L; CEM-214, 0.5mg/L; NAc-CEM-101, 0.5mg/L; and azithromycin, 2mg/L. Solithromycin showed 34-fold greater activity against Ureaplasma spp. isolates than azithromycin, whilst CEM-214 and NAc-CEM-101 possessed ca. 22% and 17% of the activity of solithromycin, respectively, significantly greater than that of azithromycin. One bacterial isolate showed resistance to azithromycin (MIC=16 mg/L) but had a much lower MIC for solithromycin (MIC=0.25mg/L). In conclusion, the metabolites of solithromycin had reduced, but still potent, activity against 100 clinical Ureaplasma spp. isolates in vitro. This may be important in some instances such as pregnancy, however studies to determine levels of the metabolites in these settings are required. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  3. Determination of long-lived natural Ra isotopes, 226Ra, in mineral and spring waters from Caxambu (MG) and Aguas de Lindoia (SP) spas

    International Nuclear Information System (INIS)

    Negrao, Sergio Garcia

    2012-01-01

    The aim of this work was to study the long-lived Ra isotopes, 226 Ra and 228 Ra, natural distribution in mineral and spring waters from Caxambu (MG) and Aguas de Lindoia (SP) water parks. In Caxambu mineral waters it was observed 228 Ra activity concentrations slightly higher than those of 226 Ra. The elevated content of carbonates and bicarbonates of these waters can result in an increased solubility of the both Ra isotopes and may play an important role for the fate of 228 Ra and its equilibrium distribution between solid and liquid phases. In Caxambu Thermal Spa, arithmetic mean activities ranged from 83 mBq L -1 to 3599 mBq L -1 and from 60 mBq L -1 to 4481 mBq L -1 for 226 Ra and 228 Ra, respectively. The highest 226 Ra activity was found in Venancio Spring, while the maximum 228 Ra activity value was determined in Ernestina Guedes. 228 Ra/ 226 Ra activity ratios varied from 0.079 (Conde D'Eau and Princesa Isabel Spring) to 4.2 (Mairink II Spring). In Aguas de Lindoia, arithmetic mean activities ranged from 4.6 mBq L -1 to 41 mBq L -1 and from 30 mBq L -1 to 54 mBq L -1 for 226 Ra and 228 Ra, respectively. The maximum 226 Ra activity concentration was found in the bottled mineral water Sao Jorge, while the higher 228 Ra activity concentration was determined in Santa Filomena Spring (public station 2). 228 Ra/ 226 Ra activity ratios varied from 1.2 (bottled mineral water Sao Jorge) to 9.1 (bottled mineral water Jatoba 1). This work also performed the dose assessment due to the ingestion of 226 Ra and 228 Ra in Caxambu and Aguas de Lindoia mineral and spring waters. The committed effective doses were estimated by using a conservative dosimetric model and taking into account the results over a lifetime (70 years) following intake of both long-lived Ra isotopes. The results from this radiological evaluation showed that the guidance committed effective dose level of 0.1 mSv y-1 recommended by World Health Organization was exceeded in almost all samples studied in

  4. 226Ra and 228Ra in scale and sludge samples and their correlation with the chemical composition.

    Science.gov (United States)

    Godoy, José Marcus; da Cruz, Rosana Petinatti

    2003-01-01

    In order to contribute to a future waste management policy related to the presence of technologically enhanced natural occurring radioactive material (TENORM) in the Brazilian petroleum industry, the present work presents the chemical composition and the (226)Ra and (228)Ra content of sludge and scales generated during the offshore E and P petroleum activities in the Campos Basin, the primary offshore oil production region in Brazil. The (226)Ra and (228)Ra content on 36 sludge and scales samples were determined by gamma-spectrometry. Based on X-ray diffractometry results, a chemical analysis schema for these samples was developed. The results have shown that scales are 75% barium and strontium sulfates, with a mean (226)Ra and (228)Ra content of 106 kBq kg(-1) and 78 kBq kg(-1), respectively. On the other hand, sludge samples have a much more complex chemical composition than the scales. The (226)Ra and (228)Ra content in sludge also varies much more than the content observed in the scales samples and ranged from 0.36 to 367 kBq kg(-1) and 0.25 to 343 kBq kg(-1), respectively.

  5. Anti-allodynic effects of N-demethylsinomenine, an active metabolite of sinomenine, in a mouse model of postoperative pain.

    Science.gov (United States)

    Ou, Yuntao; Su, Man; Ling, Yong; Wei, Qianqian; Pan, Fei; Li, Jiejia; Li, Jun-Xu; Zhu, Qing

    2018-03-15

    Sinomenine, a major bioactive ingredient isolated from traditional Chinese medicine Sinomenium acutum, has been reported to have analgesic effects in various pain animal models. N-demethylsinomenine, the N-demethylated product of sinomenine, has been identified to be the major metabolite of sinomenine and is also a natural component extracted from Sinomenium acutum. This study examined the anti-allodynic effects of N-demethylsinomenine in a mouse model of postoperative pain. A significant and sustained mechanical allodynia that lasted for 4 days was induced by making a surgical incision on the right hind paw in mice. Acute treatment with N-demethylsinomenine (10-40 mg/kg, s.c.) relieved the mechanical allodynia in a dose-dependent manner. Although there was no difference in maximal analgesic effect between N-demethylsinomenine (40 mg/kg, s.c.) and sinomenine (40 mg/kg, s.c.), the onset of action of N-demethylsinomenine was quicker than sinomenine. Repeated treatment with N-demethylsinomenine (10-40 mg/kg/day, s.c.) also dose-dependently exerted sustained antinociception against postoperative allodynia and did not produce analgesic tolerance and carry-over effect. The anti-allodynia induced by N-demethylsinomenine (40 mg/kg, s.c.) was attenuated by bicuculline, a selective γ-aminobutyric acid type A (GABA A ) receptor antagonist. In addition, the doses of N-demethylsinomenine used here did not alter the locomotor activity in mice. Our findings demonstrated that N-demethylsinomenine exerts behaviorally-specific anti-allodynia against postoperative allodynia mediated through the GABA A receptors, suggesting it may be a useful novel pharmacotherapy for the control of postoperative pain. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Effects of Body Size and Gender on the Population Pharmacokinetics of Artesunate and Its Active Metabolite Dihydroartemisinin in Pediatric Malaria Patients

    OpenAIRE

    Morris, Carrie A.; Tan, Beesan; Duparc, Stephan; Borghini-Fuhrer, Isabelle; Jung, Donald; Shin, Chang-Sik; Fleckenstein, Lawrence

    2013-01-01

    Despite the important role of the antimalarial artesunate and its active metabolite dihydroartemisinin (DHA) in malaria treatment efforts, there are limited data on the pharmacokinetics of these agents in pediatric patients. This study evaluated the effects of body size and gender on the pharmacokinetics of artesunate-DHA using data from pediatric and adult malaria patients. Nonlinear mixed-effects modeling was used to obtain a base model consisting of first-order artesunate absorption and on...

  7. Migration of 226 Ra, 228 Ra, 210 Pb, U and Th from phosphogypsum

    International Nuclear Information System (INIS)

    Silva, Nivaldo Carlos da; Cipriani, Moacir; Taddei, Maria Helena T.

    2002-01-01

    The physico-chemical availability of radioactive elements ( 210 Pb, 226 Ra, 228 Ra, Th and U) in Brazilian phosphogypsum was investigated in a large scale leaching experiment carried out in lysimeters, using phosphogypsum samples (approximately 1.2 tons) from two phosphoric acid industries. Lysimeters were built using cylindrical concrete containers with 0.9 m inner diameter and 2 m depth. The bottom of the lysimeter was filled with a 10 cm layer of gravel covered with geomembrane sheet. Under this layer a pipe was designed to drain the percolated water. Three lysimeters were filled with phosphogypsum from each industry and a mixture of both. As percolated water comes exclusively from the rain, sample was collected daily when available. Samples were then pooled weekly, carefully prepared and submitted to radiochemical analysis. Radiochemical characterization of phosphogypsum and percolated water was performed by radiochemical separation followed by gross alpha and beta counting ( 226 Ra, 228 Ra and 210 Pb) and UV-Vis spectrophotometry with Arsenazo III (U and Th). This experiment was carried out from 12/01/1999 to 01/22/2001, with a precipitation of 2,732 mm. It was observed that approximately 40% (534 L) of the rain fall percolated through the lysimeter 1. The analysis of 22 samples of percolated water from lysimeter 1 showed mean radionuclides activities of 70±30 mBqL -1 , 70±50 mBqL -1 , 100±60 mBqL -1 and 110±55 mBqL -1 for U, 226 Ra, 228 Ra and 210 Pb, respectively. Thorium activities were below detection limit. (author)

  8. RA reactor operation and maintenance in 1992, Part 1

    International Nuclear Information System (INIS)

    Sotic, O.; Cupac, S.; Sulem, B.; Zivotic, Z.; Majstorovic, D.; Tanaskovic, M.

    1992-01-01

    During 1992 Ra reactor was not in operation. All the activities were fulfilled according to the previously adopted plan. Basic activities were concerned with revitalisation of the RA reactor and maintenance of reactor components. All the reactor personnel was busy with reconstruction and renewal of the existing reactor systems and building of the new systems, maintenance of the reactor devices. Part of the staff was trained for relevant tasks and maintenance of reactor systems [sr

  9. Screening of the in vitro antileishmanial activities of compounds and secondary metabolites isolated from Maytenus guianensis Klotzsch ex Reissek (Celastraceae chichuá Amazon

    Directory of Open Access Journals (Sweden)

    Dionatas Ulises de Oliveira Meneguetti

    Full Text Available Abstract INTRODUCTION Maytenus guianensis is a member of the Celastraceae family that is used in traditional medicine, particularly for its anti-parasitic and anti-cancer effects. To explore the ethnopharmacological potential of this plant, the present study was designed to screen the in vitro antileishmanial activities of extracts and compounds isolated from M. guianensis. METHODS Maytenus guianensis stems and leaves were extracted in acetone, followed by the preparation of eluates and isolation of secondary metabolites using chromatography on a glass column with silica gel as the fixed phase. The chemical components were identified using spectroscopic methods, including one- and two-dimensional nuclear magnetic resonance of hydrogen-1 and carbon-13, mass spectroscopy, and infrared spectroscopy. The anti-Leishmania amazonensis activities of these eluates and compounds were evaluated by direct promastigote counting and viability assays. RESULTS It was found that the hexane bark eluate produced the strongest anti-L. amazonensis effect, with 90-100% inhibition of the promastigote form. The isolated metabolite that produced the best result was tingenone B, followed by a compound formed by the union of tingenone and tingenone B (80-90% inhibition. CONCLUSIONS Maytenus guianensis shows anti-parasite activity that warrants further investigation to determine the mechanisms underlying this antileishmanial effect and to evaluate the pharmacological potential of these eluates and isolated secondary metabolites, while minimizing any adverse effects.

  10. Screening of the in vitro antileishmanial activities of compounds and secondary metabolites isolated from Maytenus guianensis Klotzsch ex Reissek (Celastraceae) chichuá Amazon.

    Science.gov (United States)

    Meneguetti, Dionatas Ulises de Oliveira; Lima, Renato Abreu; Hurtado, Fernanda Bay; Passarini, Guilherme Matos; Macedo, Sharon Rose Aragão; Barros, Neuza Biguinati de; Oliveira, Flávio Augusto de Souza; Medeiros, Patrícia Soares de Maria de; Militão, Júlio Sancho Linhares Teixeira; Nicolete, Roberto; Facundo, Valdir Alves

    2016-01-01

    Maytenus guianensis is a member of the Celastraceae family that is used in traditional medicine, particularly for its anti-parasitic and anti-cancer effects. To explore the ethnopharmacological potential of this plant, the present study was designed to screen the in vitro antileishmanial activities of extracts and compounds isolated from M. guianensis. Maytenus guianensis stems and leaves were extracted in acetone, followed by the preparation of eluates and isolation of secondary metabolites using chromatography on a glass column with silica gel as the fixed phase. The chemical components were identified using spectroscopic methods, including one- and two-dimensional nuclear magnetic resonance of hydrogen-1 and carbon-13, mass spectroscopy, and infrared spectroscopy. The anti-Leishmania amazonensis activities of these eluates and compounds were evaluated by direct promastigote counting and viability assays. It was found that the hexane bark eluate produced the strongest anti-L. amazonensis effect, with 90-100% inhibition of the promastigote form. The isolated metabolite that produced the best result was tingenone B, followed by a compound formed by the union of tingenone and tingenone B (80-90% inhibition). Maytenus guianensis shows anti-parasite activity that warrants further investigation to determine the mechanisms underlying this antileishmanial effect and to evaluate the pharmacological potential of these eluates and isolated secondary metabolites, while minimizing any adverse effects.

  11. SOS response in bacteria: Inhibitory activity of lichen secondary metabolites against Escherichia coli RecA protein.

    Science.gov (United States)

    Bellio, Pierangelo; Di Pietro, Letizia; Mancini, Alisia; Piovano, Marisa; Nicoletti, Marcello; Brisdelli, Fabrizia; Tondi, Donatella; Cendron, Laura; Franceschini, Nicola; Amicosante, Gianfranco; Perilli, Mariagrazia; Celenza, Giuseppe

    2017-06-15

    RecA is a bacterial multifunctional protein essential to genetic recombination, error-prone replicative bypass of DNA damages and regulation of SOS response. The activation of bacterial SOS response is directly related to the development of intrinsic and/or acquired resistance to antimicrobials. Although recent studies directed towards RecA inactivation via ATP binding inhibition described a variety of micromolar affinity ligands, inhibitors of the DNA binding site are still unknown. Twenty-seven secondary metabolites classified as anthraquinones, depsides, depsidones, dibenzofurans, diphenyl-butenolides, paraconic acids, pseudo-depsidones, triterpenes and xanthones, were investigated for their ability to inhibit RecA from Escherichia coli. They were isolated in various Chilean regions from 14 families and 19 genera of lichens. The ATP hydrolytic activity of RecA was quantified detecting the generation of free phosphate in solution. The percentage of inhibition was calculated fixing at 100µM the concentration of the compounds. Deeper investigations were reserved to those compounds showing an inhibition higher than 80%. To clarify the mechanism of inhibition, the semi-log plot of the percentage of inhibition vs. ATP and vs. ssDNA, was evaluated. Only nine compounds showed a percentage of RecA inhibition higher than 80% (divaricatic, perlatolic, alpha-collatolic, lobaric, lichesterinic, protolichesterinic, epiphorellic acids, sphaerophorin and tumidulin). The half-inhibitory concentrations (IC 50 ) calculated for these compounds were ranging from 14.2µM for protolichesterinic acid to 42.6µM for sphaerophorin. Investigations on the mechanism of inhibition showed that all compounds behaved as uncompetitive inhibitors for ATP binding site, with the exception of epiphorellic acid which clearly acted as non-competitive inhibitor of the ATP site. Further investigations demonstrated that epiphorellic acid competitively binds the ssDNA binding site. Kinetic data were

  12. Concentration in activity of {sup 137} Cs, {sup 40} K, {sup 232} Th, {sup 226} Ra in waste deposits of the benefits of minerals in the State of Zacatecas; Concentracion en actividad de {sup 137} Cs, {sup 40} K, {sup 232} Th, {sup 226} Ra en depositos de desecho del beneficio de minerales en el Estado de Zacatecas

    Energy Technology Data Exchange (ETDEWEB)

    Leal, B.; Mireles, F.; Quirino, L.; Davila, I.; Ramirez, F. [UAZ, A.P. 579C, 98068 Zacatecas (Mexico)

    2003-07-01

    The necessity to report the changes in the contained radionuclides in the terrestrial crust, or those deposited by the atomic tests around the world, becomes clear when observing the use of material of waste of those mines. With the purpose of quantifying the concentration in activity its were meet a series of waste samples in mines of the municipalities of Zacatecas, Fresnillo, Guadalupe and Veta Grande of the state of Zacatecas, Mexico. The analysis was carried out by gamma spectrometry with a HPGe detector with a resolution of 1.9 keV corresponding to an energy of 1.33 MeV calibrated in efficiency and energy by means of a certified standard multi nuclide in activity with identical geometry to that of the samples. The times of count are of 80000 seconds, with the purpose of to reduce the relative uncertainties and to define well the interest regions. The activity of {sup 226} Ra and {sup 232} Th is obtained through the one {sup 214} Bi and {sup 228} Ac respectively, the concentration was also measured in activity of the one {sup 40} K and the {sup 137} Cs in units of Bq kg{sup -1}. (Author)

  13. The rapid mode of calcium uptake into heart mitochondria (RaM): comparison to RaM in liver mitochondria.

    Science.gov (United States)

    Buntinas, L; Gunter, K K; Sparagna, G C; Gunter, T E

    2001-04-02

    A mechanism of Ca(2+) uptake, capable of sequestering significant amounts of Ca(2+) from cytosolic Ca(2+) pulses, has previously been identified in liver mitochondria. This mechanism, the Rapid Mode of Ca(2+) uptake (RaM), was shown to sequester Ca(2+) very rapidly at the beginning of each pulse in a sequence [Sparagna et al. (1995) J. Biol. Chem. 270, 27510-27515]. The existence and properties of RaM in heart mitochondria, however, are unknown and are the basis for this study. We show that RaM functions in heart mitochondria with some of the characteristics of RaM in liver, but its activation and inhibition are quite different. It is feasible that these differences represent different physiological adaptations in these two tissues. In both tissues, RaM is highly conductive at the beginning of a Ca(2+) pulse, but is inhibited by the rising [Ca(2+)] of the pulse itself. In heart mitochondria, the time required at low [Ca(2+)] to reestablish high Ca(2+) conductivity via RaM i.e. the 'resetting time' of RaM is much longer than in liver. RaM in liver mitochondria is strongly activated by spermine, activated by ATP or GTP and unaffected by ADP and AMP. In heart, RaM is activated much less strongly by spermine and unaffected by ATP or GTP. RaM in heart is strongly inhibited by AMP and has a biphasic response to ADP; it is activated at low concentrations and inhibited at high concentrations. Finally, an hypothesis consistent with the data and characteristics of liver and heart is presented to explain how RaM may function to control the rate of oxidative phosphorylation in each tissue. Under this hypothesis, RaM functions to create a brief, high free Ca(2+) concentration inside mitochondria which may activate intramitochondrial metabolic reactions with relatively small amounts of Ca(2+) uptake. This hypothesis is consistent with the view that intramitochondrial [Ca(2+)] may be used to control the rate of ADP phosphorylation in such a way as to minimize the probability of

  14. From patients with arthralgia, pre-RA and recently diagnosed RA: What is the current status of understanding RA pathogenesis?

    NARCIS (Netherlands)

    M. Molendijk (Marlieke); J.M.W. Hazes (Mieke); E.W. Lubberts (Erik)

    2018-01-01

    textabstractIt is believed that therapy for rheumatoid arthritis (RA) is the most effective and beneficial within a short time frame around RA diagnosis. This insight has caused a shift from research in patients with established RA to patients at risk of developing RA and recently diagnosed

  15. Research nuclear reactor RA - Annual report 1992; Istrazivacki nuklearni reaktor RA - Izvestaj za 1992. godinu

    Energy Technology Data Exchange (ETDEWEB)

    Sotic, O [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

    1992-12-01

    Research reactor RA Annual report for year 1992 is divided into two main parts to cover: (1) operation and maintenance and (2) activities related to radiation protection. First part includes 8 annexes describing reactor operation, activities of services for maintenance of reactor components and instrumentation, financial report and staffing. Second annex B is a paper by Z. Vukadin 'Recurrence formulas for evaluating expansion series of depletion functions' published in 'Kerntechnik' 56, (1991) No.6 (INIS record no. 23024136. Second part of the report is devoted to radiation protection issues and contains 4 annexes with data about radiation control of the working environment and reactor environment, description of decontamination activities, collection of radioactive wastes, and meteorology data. [Serbo-Croat] Godisnji izvestaj o radu nuklearnog reaktora RA za 1992. godinu sastoji se od dva dela: prvi deo obuhvata pogon i odzavanje reaktora RA, a drugi poslove zastite od zracenja na reaktoru RA. Prvi deo sadrzi 8 priloga, koji opisuju rad reaktora i poslove sluzbi za odrzavanje opreme i komponenti, finansijski izvestaj, kadrovsku strukturu osoblja reaktora. Drugi prilog (B) je rad Z. Vukadina 'Recurrence formulas for evaluating expansion series of depletion functions' objavljen u casopisu Kerntechnik, 1991. Drugi deo izvestaja o poslovima zastite od zracenja sadrzi 4 priloga sa podacima radijacione kontrole radne sredine i okoline reaktora, opis poslova dekontaminacije i sakupljanja radioaktivnih materija, kao i meteoroloske podatke.

  16. Antioxidant Enzyme Activities and Secondary Metabolite Profiling of Oil Palm Seedlings Treated with Combination of NPK Fertilizers Infected with Ganoderma boninense

    Science.gov (United States)

    Mohidin, Hasmah; Idris, Abu Seman; Fariz, A.; Abiri, Rambod; Taheri, Sima; Moradpoor, Mehdi

    2018-01-01

    Oil palm (Elaeis guineensis Jacq) is one of the major sources of edible oil. Reducing the effect of Ganoderma, main cause of basal stem rot (BSR) on oil palm, is the main propose of this study. Understanding the oil palm defense mechanism against Ganoderma infection through monitoring changes in the secondary metabolite compounds levels before/after infection by Ganoderma under different fertilizing treatment is required. Oil palm requires macro- and microelements for growth and yield. Manipulating the nutrient for oil palm is a method to control the disease. The 3-4-month-old oil palm seedlings were given different macronutrient treatments to evaluate induction of defense related enzymes and production of secondary metabolite compounds in response to G. boninense inoculation. The observed trend of changes in the infected and uninfected seedlings was a slightly higher activity for β-1,3-glucanases, chitinase, peroxidase, and phenylalanine ammonia-lyase during the process of pathogenesis. It was found that PR proteins gave positive response to the interaction between oil palm seedlings and Ganoderma infection. Although the responses were activated systematically, they were short-lasting as the changes in enzymes activities appeared before the occurrence of visible symptoms. Effect of different nutrients doses was obviously observed among the results of the secondary metabolite compounds. Many identified/unidentified metabolite compounds were presented, of which some were involved in plant cell defense mechanism against pathogens, mostly belonging to alkaloids with bitter-tasting nitrogenous-compounds, and some had the potential to be used as new markers to detect basal stem rot at the initial step of disease. PMID:29721500

  17. Antioxidant Enzyme Activities and Secondary Metabolite Profiling of Oil Palm Seedlings Treated with Combination of NPK Fertilizers Infected with Ganoderma boninense.

    Science.gov (United States)

    Sahebi, Mahbod; Hanafi, Mohamed M; Mohidin, Hasmah; Rafii, M Y; Azizi, Parisa; Idris, Abu Seman; Fariz, A; Abiri, Rambod; Taheri, Sima; Moradpoor, Mehdi

    2018-01-01

    Oil palm ( Elaeis guineensis Jacq) is one of the major sources of edible oil. Reducing the effect of Ganoderma, main cause of basal stem rot (BSR) on oil palm, is the main propose of this study. Understanding the oil palm defense mechanism against Ganoderma infection through monitoring changes in the secondary metabolite compounds levels before/after infection by Ganoderma under different fertilizing treatment is required. Oil palm requires macro- and microelements for growth and yield. Manipulating the nutrient for oil palm is a method to control the disease. The 3-4-month-old oil palm seedlings were given different macronutrient treatments to evaluate induction of defense related enzymes and production of secondary metabolite compounds in response to G. boninense inoculation. The observed trend of changes in the infected and uninfected seedlings was a slightly higher activity for β -1,3-glucanases, chitinase, peroxidase, and phenylalanine ammonia-lyase during the process of pathogenesis. It was found that PR proteins gave positive response to the interaction between oil palm seedlings and Ganoderma infection. Although the responses were activated systematically, they were short-lasting as the changes in enzymes activities appeared before the occurrence of visible symptoms. Effect of different nutrients doses was obviously observed among the results of the secondary metabolite compounds. Many identified/unidentified metabolite compounds were presented, of which some were involved in plant cell defense mechanism against pathogens, mostly belonging to alkaloids with bitter-tasting nitrogenous-compounds, and some had the potential to be used as new markers to detect basal stem rot at the initial step of disease.

  18. Antioxidant Enzyme Activities and Secondary Metabolite Profiling of Oil Palm Seedlings Treated with Combination of NPK Fertilizers Infected with Ganoderma boninense

    Directory of Open Access Journals (Sweden)

    Mahbod Sahebi

    2018-01-01

    Full Text Available Oil palm (Elaeis guineensis Jacq is one of the major sources of edible oil. Reducing the effect of Ganoderma, main cause of basal stem rot (BSR on oil palm, is the main propose of this study. Understanding the oil palm defense mechanism against Ganoderma infection through monitoring changes in the secondary metabolite compounds levels before/after infection by Ganoderma under different fertilizing treatment is required. Oil palm requires macro- and microelements for growth and yield. Manipulating the nutrient for oil palm is a method to control the disease. The 3-4-month-old oil palm seedlings were given different macronutrient treatments to evaluate induction of defense related enzymes and production of secondary metabolite compounds in response to G. boninense inoculation. The observed trend of changes in the infected and uninfected seedlings was a slightly higher activity for β-1,3-glucanases, chitinase, peroxidase, and phenylalanine ammonia-lyase during the process of pathogenesis. It was found that PR proteins gave positive response to the interaction between oil palm seedlings and Ganoderma infection. Although the responses were activated systematically, they were short-lasting as the changes in enzymes activities appeared before the occurrence of visible symptoms. Effect of different nutrients doses was obviously observed among the results of the secondary metabolite compounds. Many identified/unidentified metabolite compounds were presented, of which some were involved in plant cell defense mechanism against pathogens, mostly belonging to alkaloids with bitter-tasting nitrogenous-compounds, and some had the potential to be used as new markers to detect basal stem rot at the initial step of disease.

  19. Regulations for RA reactor operation; Propisi nuklearnog reaktora 'RA'

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1980-09-15

    Regulations for RA reactor operation are written in accordance with the legal regulations defined by the Law about radiation protection and related legal acts, as well as technical standards according to the IAEA recommendations. The contents of this book include: fundamental data about the reactor; legal regulations for reactor operation; organizational scheme for reactor operation; general and detailed instructions for operation, behaviour in the reactor building, performing experiments; operating rules for operation under steady state and accidental conditions. [Serbo-Croat] Propisi o radu nuklearnog reaktora RA pisani su tako da svi zakonski propisi definisani 'Zakonom o zastiti od jonizujuceg zracenja' i pratecim propisima (devet pravilnika) kao i tehnicke norme prema preporukama MAAE budu postovani u punoj meri pri radu reaktora. Sadrzaj ove knjige obuhvata: osnovne podatke o reaktoru; zakonske propise; organizaciju rada reaktora RA; opste propise o rezimu rada, kretanju u zgradi reaktora, izvodjenju eksperimenata; pogonske propise za rad u normalnom rezimu i u slucaju udesa.

  20. Effect of gemfibrozil and rifampicin on the pharmacokinetics of selexipag and its active metabolite in healthy subjects.

    Science.gov (United States)

    Bruderer, Shirin; Petersen-Sylla, Marc; Boehler, Margaux; Remeňová, Tatiana; Halabi, Atef; Dingemanse, Jasper

    2017-12-01

    Based on in vitro data, there is evidence to suggest that cytochrome P450 (CYP) 2C8 is involved in the metabolism of selexipag and its active metabolite, ACT-333679. The present study evaluated the possible pharmacokinetic interactions of selexipag with gemfibrozil, a strong CYP2C8 inhibitor, and rifampicin, an inducer of CYP2C8. The study consisted of two independent parts, each conducted according to an open-label, randomized, crossover design. The pharmacokinetics and safety of selexipag and ACT-333679 were studied following single-dose administration either alone or in the presence of multiple-dose gemfibrozil (part I) or rifampicin (part II) in healthy male subjects. Gemfibrozil had comparatively small effects on selexipag (less than 2-fold difference in any pharmacokinetic variable) but, with respect to ACT-333679, increased the maximum plasma concentration (C max ) 3.6-fold [90% confidence interval (CI) 3.1, 4.3] and the area under the plasma concentration-time curve from zero to infinity (AUC 0-∞ ) 11.1-fold (90% CI 9.2, 13.4). The marked increased exposure to ACT-333679, which mediates the majority of the pharmacological activity of selexipag, was accompanied by significantly more adverse events such as headache, nausea and vomiting. Coadministration of rifampicin increased the C max of selexipag 1.8-fold (90% CI 1.4, 2.2) and its AUC0 -∞ 1.3-fold (90% CI 1.1, 1.4); its effects on ACT-333679 were to increase its C max 1.3-fold (90% CI 1.1, 1.6), shorten its half-life by 63% and reduce its AUC0 -∞ by half (90% CI 0.45, 0.59). Concomitant administration of selexipag and strong inhibitors of CYP2C8 must be avoided, whereas when coadministered with inducers of CYP2C8, dose adjustments of selexipag should be envisaged. © 2017 The British Pharmacological Society.

  1. Research nuclear reactor RA - Annual Report 1991; Istrazivacki nuklearni reaktor RA - Izvestaj za 1991. godinu

    Energy Technology Data Exchange (ETDEWEB)

    Sotic, O [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

    1992-01-01

    Activities related to revitalisation of the RA reactor stared in 1986, were continued in 1991. A number of interventions on the reactor components were finished that are supposed to enable continuous and reliable operation. The last, and at the same time largest action, related to exchange of complete reactor instrumentation is underway, but it is behind the schedule in 1991 because the delivery of components from USSR is late. Production of this instruments is financed by the IAEA according to the contract signed in December 1988 with Russian Atomenergoexport. According to this contract, it has been planned that the RA reactor instrumentation should be delivered to the Vinca Institute by the end of 1990. Only 56% of the instrumentation was delivered until September 1991. Since then any delivery of components to Yugoslavia was stopped because of the temporary embargo imposed by the IAEA. In 1991 most of the existing RA reactor instrumentation was dismantled, only the part needed for basic measurements when reactor is not operated, was maintained. Construction of some support elements is almost finished by the local staff. The Institute has undertaken this activity in order to speed up the ending of the project. If all the planned instrumentation would not arrive until the end of March 1992, it would not be possible to start the RA reactor testing operation in the first part of 1993, as previously planned. In 1991, 53 staff members took part in the activities during 1991, which is considered sufficient for maintenance and repair conditions. Research reactor RA Annual report for year 1991 is divided into two main parts to cover: (1) operation and maintenance and (2) activities related to radiation protection. [Serbo-Croat] U 1991. godini nastavljeni su poslovi na revitalizaciji reaktora RA, zapocetoj 1986. godine. Okoncan je niz zahvata na opremi postrojenja kojima ce se u narednom periodu omoguciti kontinualan i pouzdan rad ovog reaktora. Poslednji, i ujedno najveci

  2. The association of fatigue, comorbidity burden, disease activity, disability and gross domestic product in patients with rheumatoid arthritis. Results from 34 countries participating in the Quest-RA program.

    Science.gov (United States)

    Grøn, Kathrine Lederballe; Ornbjerg, Lykke Midtbøll; Hetland, Merete Lund; Aslam, Fawad; Khan, Nasim A; Jacobs, Johannes W G; Henrohn, Dan; Rasker, J J; Kauppi, Markku J; Lang, Hui-Chu; Mota, Licia M H; Aggarwal, Amita; Yamanaka, Hisahi; Badsha, Humeira; Gossec, Laure; Cutolo, Maurizio; Ferraccioli, Gianfranco; Gremese, Elisa; Bong Lee, Eun; Inanc, Nevsun; Direskeneli, Haner; Taylor, Peter; Huisman, Margriet; Alten, Rieke; Pohl, Christoph; Oyoo, Omondi; Stropuviene, Sigita; Drosos, Alexandrosos A; Kerzberg, Eduardo; Ancuta, Codorina; Mofti, Ayman; Bergman, Martin; Detert, Jaqueline; Selim, Zaraa I; Abda, Essam A; Rexhepi, Blerta; Sokka, Tuulikki

    2014-01-01

    The aim is to assess the prevalence of comorbidities and to further analyse to which degree fatigue can be explained by comorbidity burden, disease activity, disability and gross domestic product (GDP) in patients with rheumatoid arthritis (RA). Nine thousands eight hundred seventy-four patients from 34 countries, 16 with high GDP (>24.000 US dollars [USD] per capita) and 18 low-GDP countries (6.6) compared with 23.0% in high-GDP countries (p<0.001). In univariate analysis, fatigue increased with increasing number of comorbidities, disease activity and disability in both high- and low-GDP countries. In multivariate analysis of all countries, these 3 variables explained 29.4% of the variability, whereas GDP was not significant. Fatigue is a widespread problem associated with high comorbidity burden, disease activity and disability regardless of GDP.

  3. In vitro fermentation of prebiotics by Lactobacillus plantarum CFR 2194: selectivity, viability and effect of metabolites on β-glucuronidase activity.

    Science.gov (United States)

    Arenahalli Ningegowda, Madhu; Siddalingaiya Gurudutt, Prapulla

    2012-03-01

    Prebiotic Fructooligosaccharides (FOS) escape metabolism in upper GI tract undergo microbial metabolism in colon and thereby influence the nature, type and number of intestinal microbiota to improve host's health. The present study focuses on the ability of Lactobacillus plantarum CFR 2194 to utilize FOS as a selective carbon and energy source. The effect of fermentative metabolites of L. plantarum on the β-glucuronidase was also investigated. A total of 16 strains of lactobacilli were assessed for their ability to ferment oligosaccharides. L. plantarum CFR 2194, an isolate from kanjika was found to utilize FOS effectively. Lactic acid was the main metabolic end product, followed by acetic acid, butyric acid, formic acid and ethanol. The inhibitory effects of these metabolites have been confirmed through the reduction of β-glucuronidase activity. L. plantarum when co-cultured with β-glucuronidase producing E. coli, in a basal media containing FOS as an energy source, could inhibit the growth of the pathogen during the course of fermentation. The results showed that L. plantarum CFR 2194 has the ability to utilize the prebiotic FOS as a selective carbon and energy source. The organism could inhibit the growth of the pathogen which produces β-glucuronidase and lowered its activity by the metabolites of FOS which indicates the probable use of L. plantarum through dietary intervention in combating colon carcinogenesis.

  4. Structure-activity relationships for the fluorescence of ochratoxin A: Insight for detection of ochratoxin A metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Frenette, Christine; Paugh, Robert J. [Departments of Chemistry and Toxicology, University of Guelph, Guelph, Ontario, N1G 2W1 (Canada); Tozlovanu, Mariana; Juzio, Maud [ENSAT, UMR CNRS 5503, 1 Avenue Agrobiopole 31326 Auzeville-Tolosane (France); Pfohl-Leszkowicz, Annie [ENSAT, UMR CNRS 5503, 1 Avenue Agrobiopole 31326 Auzeville-Tolosane (France)], E-mail: leszkowicz@ensat.fr; Manderville, Richard A. [Departments of Chemistry and Toxicology, University of Guelph, Guelph, Ontario, N1G 2W1 (Canada)], E-mail: rmanderv@uoguelph.ca

    2008-06-09

    Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium that is widely found as a contaminant of food products. The toxin is a renal carcinogen in male rats, the cause of mycotoxicoses in pigs and has been associated with chronic human kidney diseases. Bioactivation has been implicated in OTA-mediated toxicity, although inconsistent results have been reported, due, in part, to the difficulty in detecting OTA metabolites in vivo. Liquid chromatography (LC) coupled with fluorescence detection (FLD) is the most widely used analytical detection method for OTA. Under acidic conditions the toxin generates blue fluorescence (465 nm) that is due to an excited state intramolecular proton transfer (ESIPT) process that generates an emissive keto tautomer. Disruption of this ESIPT process quenches fluorescence intensity and causes a blue shift in emission maxima. The aim of the present study was to determine the impact of the C5-chlorine atom, the lactone moiety and the amide bond on OTA fluorescence and derive optical parameters for OTA metabolites that have been detected in vitro. Our results highlight the limitations of LC/FLD for OTA metabolites that do not undergo ESIPT. For emissive derivatives, our absorption and emission data improves the sensitivity of LC/FLD (3-4-fold increase in the limit of detection (LOD)) for OTA analogues bearing a C5-OH group, such as the hydroquinone (OTHQ) metabolite and the glutathione conjugate of OTA (OTA-GSH). This increased sensitivity may facilitate the detection of OTA metabolites bearing a C5-OH group in biological fluids and enhance our understanding of OTA-mediated toxicity.

  5. Seasonal changes in submarine groundwater discharge to coastal salt ponds estimated using 226Ra and 228Ra as tracers

    Science.gov (United States)

    Hougham, A.L.; Moran, S.B.; Masterson, J.P.; Kelly, R.P.

    2008-01-01

    Submarine groundwater discharge (SGD) to coastal southern Rhode Island was estimated from measurements of the naturally-occurring radioisotopes 226Ra (t1/2 = 1600??y) and 228Ra (t1/2 = 5.75??y). Surface water and porewater samples were collected quarterly in Winnapaug, Quonochontaug, Ninigret, Green Hill, and Pt. Judith-Potter Ponds, as well as nearly monthly in the surface water of Rhode Island Sound, from January 2002 to August 2003; additional porewater samples were collected in August 2005. Surface water activities ranged from 12-83??dpm 100??L- 1 (60??dpm = 1??Bq) and 21-256??dpm 100??L- 1 for 226Ra and 228Ra, respectively. Porewater 226Ra activities ranged from 16-736??dpm 100??L- 1 (2002-2003) and 95-815??dpm 100??L- 1 (2005), while porewater 228Ra activities ranged from 23-1265??dpm 100??L- 1. Combining these data with a simple box model provided average 226Ra-based submarine groundwater fluxes ranging from 11-159??L m- 2 d- 1 and average 228Ra-derived fluxes of 15-259??L m- 2 d- 1. Seasonal changes in Ra-derived SGD were apparent in all ponds as well as between ponds, with SGD values of 30-472??L m- 2 d- 1 (Winnapaug Pond), 6-20??L m- 2 d- 1 (Quonochontaug Pond), 36-273??L m- 2 d- 1 (Ninigret Pond), 29-76??L m- 2 d- 1 (Green Hill Pond), and 19-83??L m- 2 d- 1 (Pt. Judith-Potter Pond). These Ra-derived fluxes are up to two orders of magnitude higher than results predicted by a numerical model of groundwater flow, estimates of aquifer recharge for the study period, and values published in previous Ra-based SGD studies in Rhode Island. This disparity may result from differences in the type of flow (recirculated seawater versus fresh groundwater) determined using each technique, as well as variability in porewater Ra activity. ?? 2007 Elsevier B.V. All rights reserved.

  6. Hydroxyapatite particles as carriers for "2"2"3Ra

    International Nuclear Information System (INIS)

    Vasiliev, A.N.

    2017-01-01

    Systematic investigation of optimal conditions for preparation and in vitro stability of HAP particles labeled with "2"2"3Ra, that could be considered as promising candidates for targeted α-therapy, has been carried out. Two different approaches to HAP labelling were tested: sorption of Ra"2"+ on pre-synthesized HAP-particles and incorporation of Ra"2"+ into the structure of HAP during its synthesis. Two textural forms of HAP particles were used-nanoparticles and particles with the diameter of 350 ± 20 μm. Kinetics of "2"2"3Ra sorption on HAP of different particle size and desorption in 0.9 % NaCl solution were studied. The influence of solution acidity and solid to liquid phase ratio on sorption of Ra was evaluated and the sorption yield up to 98 % was achieved. It was found that the optimal conditions for the sorption included synthesis of HAP nanoparticles in the presence of "2"2"3Ra at pH values of 4-7 followed by annealing at 900 deg C. In this case subsequent cumulative desorption of Ra was <5 % of initial activity. (author)

  7. Development of a liquid scintillation method for in vitro determination of 226Ra and 228 Ra in bioassay samples

    International Nuclear Information System (INIS)

    Fernandes, Paulo Cesar P.; Sousa, Wanderson O.; Juliao, Ligia M.Q.C.; Dantas, Bernardo M.

    2011-01-01

    Radium isotopes are dispersed in the environment according to their physicochemical characteristics. The intake of 226 Ra and 228 Ra in humans can occur by inhalation and ingestion and the risk of internal exposure are related to their long half-lives, characteristics of the emission and biokinetics of the isotopes in the human body. The goal of this work is to develop a methodology for the analysis of 226 Ra and 228 Ra in excreta samples (urine and feces), using liquid scintillation technique. Excreta samples were provided by non-exposed humans for the purpose of standardizing the methodology and the establishment of a background level of radium excretion. Radium isotopes were concentrated and separated from the constituents of the sample by co-precipitation with barium sulphate. The precipitate of Ba(Ra)SO 4 was filtrated and weighted for the determination of the chemical yield. The filter containing the precipitate was transferred to a scintillation vial. In the scintillation vial, 8 mL of water, 8 mL of Instagel XF and 4 mL of UltimaGold were added, forming a gel suspension, after stirring the solution. The 226 Ra and 228 Ra activities were determined 21 days after the precipitation of samples. The samples were counted in a liquid scintillation spectrometer. The technique presented adequate sensitivity and reproducibility for the analysis of urine and feces. The activities of 226 Ra and 228 Ra in excreta samples provide useful information for the identification of the main route of intake and for the assessment of the internal exposure of occupationally exposed workers and inhabitants of high background areas. (author)

  8. Human umbilical cord-derived mesenchymal stem cells suppress proliferation of PHA-activated lymphocytes in vitro by inducing CD4(+)CD25(high)CD45RA(+) regulatory T cell production and modulating cytokine secretion.

    Science.gov (United States)

    Yang, Hongna; Sun, Jinhua; Li, Yan; Duan, Wei-Ming; Bi, Jianzhong; Qu, Tingyu

    2016-04-01

    Bone marrow-derived mesenchymal stem cells (MSCs) are promising candidate cells for therapeutic application in autoimmune diseases due to their immunomodulatory properties. Unused human umbilical cords (UC) offer an abundant and noninvasive source of MSCs without ethical issues and are emerging as a valuable alternative to bone marrow tissue for producing MSCs. We thus investigated the immunomodulation effect of umbilical cord-derived MSCs (UC-MSCs) on human peripheral blood mononuclear cells (PBMCs), T cells in particular, in a co-culture system. We found that UC-MSCs efficiently suppressed the proliferation of phytohaemagglutinin (PHA)-stimulated PBMCs (pMSCs primarily inhibited the division of generation 3 (G3) and 4 (G4) of PBMCs. In addition, UC-MSCs augmented the expression of CD127(+) and CD45RA(+) but reduced the expression of CD25(+) in PBMCs stimulated by PHA (pMSCs inhibited PHA-resulted increase in the frequency of CD4(+)CD25(+)CD127(low/-) Tregs significantly (pMSCs are able to suppress mitogen-induced PBMC activation and proliferation in vitro by altering T lymphocyte phenotypes, increasing the frequency of CD4(+)CD25(high)CD45RA(+) Tregs, and modulating the associated cytokine production. Further studies are warranted to investigate the therapeutic potential of UC-MSCs in immunologically-diseased conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Communications programme for the RA nuclear reactor decommission

    International Nuclear Information System (INIS)

    Milanovic, S.; Antic, D.

    2002-01-01

    During the decommissioning of the RA research nuclear reactor at the VINCA Institute of Nuclear Sciences, an adequate number of radiation and contamination surveys should be conduced to assure radiological safety of the workers, the public and the environment. Public would like to know more about the nuclear and radiological safety. The communications programme defines the ways to informing the public, its representatives and the information media about the health and safety aspects of the activities during the RA nuclear reactor decommission. (author)

  10. RA reactor operation and maintenance in 1992, Part 1; Deo 1 - Pogon i odrzavanje nuklearnog reaktoro RA u 1992. Godini

    Energy Technology Data Exchange (ETDEWEB)

    Sotic, O; Cupac, S; Sulem, B; Zivotic, Z; Majstorovic, D; Tanaskovic, M [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

    1992-12-01

    During 1992 Ra reactor was not in operation. All the activities were fulfilled according to the previously adopted plan. Basic activities were concerned with revitalisation of the RA reactor and maintenance of reactor components. All the reactor personnel was busy with reconstruction and renewal of the existing reactor systems and building of the new systems, maintenance of the reactor devices. Part of the staff was trained for relevant tasks and maintenance of reactor systems. [Serbo-Croat] U toku 1992 godine poslovi u okviru projekta 'Istrazivacki nuklearni reaktor RA' obavljani su u skladu sa programom i planom rada. Osnovne aktivnosti na kojima je radjeno odnosile su se na revitalizaciju reaktora RA, kao i na odrzavanje opreme. U ovom periodu reaktor nije bio u pogonu. Svo osoblje je bilo angazovano na poslovima rekonstrukcije i modernizacije postojecih i dogradnje novih reaktorskih sistema, na odrzavanju opreme a deo tehnickog osoblja je bio obucavan za vrsenje odgovarajucih poslova u pogonu i odrzavanju opreme.

  11. Development, validation and clinical application of a LC-MS/MS method for the simultaneous quantification of hydroxychloroquine and its active metabolites in human whole blood.

    Science.gov (United States)

    Soichot, Marion; Mégarbane, Bruno; Houzé, Pascal; Chevillard, Lucie; Fonsart, Julien; Baud, Frédéric J; Laprévote, Olivier; Bourgogne, Emmanuel

    2014-11-01

    A rapid, sensitive and specific method using liquid chromatography coupled to tandem mass spectrometry was developed for the simultaneous quantification of hydroxychloroquine (HCQ) and its three major metabolites in human whole blood. The assay, using a sample volume of 100μL, was linear in a dynamic 25-2000ng/mL range (R(2)>0.99) for all four compounds and suitable for the determination of elevated HCQ concentrations up to 20,000ng/mL, after appropriate sample dilution. Inter- and intra-assay precisions were <18.2% and accuracies were between 84% and 113% for any analyte. No matrix effects were observed. The assay was successfully applied to a blood sample obtained from one poisoned patient following a massive HCQ self-ingestion resulting in an estimated concentration of 19,500ng/mL on hospital admission. In this patient, HCQ metabolites were identified and quantified at 1123, 465 and 91ng/mL for monodesethylhydroxychloroquine, desethylchloroquine and bisdesethylchloroquine, respectively. Further investigations are still required to assess the usefulness of the simultaneous measurement of blood concentrations of HCQ and its three active metabolites for monitoring HCQ treatment and managing HCQ poisoning. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Population Pharmacokinetics of Telapristone (CDB-4124) and its Active Monodemethylated Metabolite CDB-4453, with a Mixture Model for Total Clearance

    OpenAIRE

    Morris, Denise; Podolski, Joseph; Kirsch, Alan; Wiehle, Ronald; Fleckenstein, Lawrence

    2011-01-01

    Telapristone is a selective progesterone antagonist that is being developed for the long-term treatment of symptoms associated with endometriosis and uterine fibroids. The population pharmacokinetics of telapristone (CDB-4124) and CDB-4453 was investigated using nonlinear mixed-effects modeling. Data from two clinical studies (n?=?32) were included in the analysis. A two-compartment (parent) one compartment (metabolite) mixture model (with two populations for apparent clearance) with first-or...

  13. Population pharmacokinetics of telapristone (CDB-4124) and its active monodemethylated metabolite CDB-4453, with a mixture model for total clearance.

    Science.gov (United States)

    Morris, Denise; Podolski, Joseph; Kirsch, Alan; Wiehle, Ronald; Fleckenstein, Lawrence

    2011-12-01

    Telapristone is a selective progesterone antagonist that is being developed for the long-term treatment of symptoms associated with endometriosis and uterine fibroids. The population pharmacokinetics of telapristone (CDB-4124) and CDB-4453 was investigated using nonlinear mixed-effects modeling. Data from two clinical studies (n = 32) were included in the analysis. A two-compartment (parent) one compartment (metabolite) mixture model (with two populations for apparent clearance) with first-order absorption and elimination adequately described the pharmacokinetics of telapristone and CDB-4453. Telapristone was rapidly absorbed with an absorption rate constant (Ka) of 1.26 h(-1). Moderate renal impairment resulted in a 74% decrease in Ka. The population estimates for oral clearance (CL/F) for the two populations were 11.6 and 3.34 L/h, respectively, with 25% of the subjects being allocated to the high-clearance group. Apparent volume of distribution for the central compartment (V2/F) was 37.4 L, apparent inter-compartmental clearance (Q/F) was 21.9 L/h, and apparent peripheral volume of distribution for the parent (V4/F) was 120 L. The ratio of the fraction of telapristone converted to CDB-4453 to the distribution volume of CDB-4453 (Fmet(est)) was 0.20/L. Apparent volume of distribution of the metabolite compartment (V3/F) was fixed to 1 L and apparent clearance of the metabolite (CLM/F) was 2.43 L/h. A two-compartment parent-metabolite model adequately described the pharmacokinetics of telapristone and CDB-4453. The clearance of telapristone was separated into two populations and could be the result of metabolism via polymorphic CYP3A5.

  14. Food contents and biological activity of 25-hydroxyvitamin D: A vitamin D metabolite to be reckoned with?

    DEFF Research Database (Denmark)

    Ovesen, Lars; Brot, C.; Jakobsen, Jette

    2003-01-01

    Only a limited number of foods naturally contain vitamin D such as fish, meat and offal, and eggs, and milk and dairy products. However, all these foods in addition contain the metabolite 25-hydroxyvitamin D (25OHD). From the few systematic studies which have been performed the food contents of 25......OHD in animal foods are usually low but vary. Contents are typically very low in milk and fish (...

  15. Drug metabolism in human brain: high levels of cytochrome P4503A43 in brain and metabolism of anti-anxiety drug alprazolam to its active metabolite.

    Directory of Open Access Journals (Sweden)

    Varsha Agarwal

    2008-06-01

    Full Text Available Cytochrome P450 (P450 is a super-family of drug metabolizing enzymes. P450 enzymes have dual function; they can metabolize drugs to pharmacologically inactive metabolites facilitating their excretion or biotransform them to pharmacologically active metabolites which may have longer half-life than the parent drug. The variable pharmacological response to psychoactive drugs typically seen in population groups is often not accountable by considering dissimilarities in hepatic metabolism. Metabolism in brain specific nuclei may play a role in pharmacological modulation of drugs acting on the CNS and help explain some of the diverse response to these drugs seen in patient population. P450 enzymes are also present in brain where drug metabolism can take place and modify therapeutic action of drugs at the site of action. We have earlier demonstrated an intrinsic difference in the biotransformation of alprazolam (ALP in brain and liver, relatively more alpha-hydroxy alprazolam (alpha-OHALP is formed in brain as compared to liver. In the present study we show that recombinant CYP3A43 metabolizes ALP to both alpha-OHALP and 4-hydroxy alprazolam (4-OHALP while CYP3A4 metabolizes ALP predominantly to its inactive metabolite, 4-OHALP. The expression of CYP3A43 mRNA in human brain samples correlates with formation of relatively higher levels of alpha-OH ALP indicating that individuals who express higher levels of CYP3A43 in the brain would generate larger amounts of alpha-OHALP. Further, the expression of CYP3A43 was relatively higher in brain as compared to liver across different ethnic populations. Since CYP3A enzymes play a prominent role in the metabolism of drugs, the higher expression of CYP3A43 would generate metabolite profile of drugs differentially in human brain and thus impact the pharmacodynamics of psychoactive drugs at the site of action.

  16. 210Pb and 226Ra distributions in the circumpolar waters

    International Nuclear Information System (INIS)

    Chung, Y.

    1981-01-01

    210 Pb and 226 Ra profiles have been measured at five GEOSECS stations in the Circumpolar region. These profiles show that 226 Ra is quite uniformly distributed throughout the Circumpolar region, with slightly lower activities in surface waters, while 210 Pb varies with depth as well as location or area. There is a subsurface 210 Pb maximum which matches the oxygen minimum in depth and roughly correlates with the temperature and salinity maxima. This 210 Pb maximum has its highest concentrations in the Atlantic sector and appears to originate near the South Sandwich Islands northeast of the Weddell Sea. Concentrations in this maximum decrease toward the Indian Ocean sector and then become fairly constant along the easterly Circumpolar Current. Relative to 226 Ra, the activity of 210 Pb is deficient in the entire water column of the Circumpolar waters. The deficiency increases from the depth of the 210 Pb maximum toward the bottom, and the 210 Pb/ 226 Ra activity ratio is lowest in the Antarctic Bottom Water, indicating a rapid removal of Pb by particulate scavenging in the bottom layer and/or a short mean residence time of the Antarctic Bottom Water in the Circumpolar region. 226 Ra is essentially linearly correlated with silica and barium in the Circumpolar waters. However, close examination of the vertical profiles reveals that Ba and Si are more variable than 226 Ra in this region. (orig.)

  17. Oral Administration of the Japanese Traditional Medicine Keishibukuryogan-ka-yokuinin Decreases Reactive Oxygen Metabolites in Rat Plasma: Identification of Chemical Constituents Contributing to Antioxidant Activity

    Directory of Open Access Journals (Sweden)

    Yosuke Matsubara

    2017-02-01

    Full Text Available Insufficient detoxification and/or overproduction of reactive oxygen species (ROS induce cellular and tissue damage, and generated reactive oxygen metabolites become exacerbating factors of dermatitis. Keishibukuryogan-ka-yokuinin (KBGY is a traditional Japanese medicine prescribed to treat dermatitis such as acne vulgaris. Our aim was to verify the antioxidant properties of KBGY, and identify its active constituents by blood pharmacokinetic techniques. Chemical constituents were quantified in extracts of KBGY, crude components, and the plasma of rats treated with a single oral administration of KBGY. Twenty-three KBGY compounds were detected in plasma, including gallic acid, prunasin, paeoniflorin, and azelaic acid, which have been reported to be effective for inflammation. KBGY decreased level of the diacron-reactive oxygen metabolites (d-ROMs in plasma. ROS-scavenging and lipid hydroperoxide (LPO generation assays revealed that gallic acid, 3-O-methylgallic acid, (+-catechin, and lariciresinol possess strong antioxidant activities. Gallic acid was active at a similar concentration to the maximum plasma concentration, therefore, our findings indicate that gallic acid is an important active constituent contributing to the antioxidant effects of KBGY. KBGY and its active constituents may improve redox imbalances induced by oxidative stress as an optional treatment for skin diseases.

  18. Production of cyathane type secondary metabolites by submerged cultures of Hericium erinaceus and evaluation of their antibacterial activity by direct bioautography.

    Science.gov (United States)

    Shen, T; Morlock, G; Zorn, H

    2015-01-01

    Fungi of the phylum Basidiomycota are well-known to form a broad spectrum of biologically active secondary metabolites, especially low molecular weight compounds such as terpenoids. Hericium erinaceus produces various cyathane type diterpenoids including erinacines. However, no quantitative data and production kinetics have been reported on the biosynthesis of the erinacines C and P in submerged cultures. In the present study, the production of erinacine C was optimized, and the product formation kinetics as well as the antimicrobial activity were studied by high-performance liquid chromatography (HPLC), high-performance thin-layer chromatography (HPTLC) and direct bioautography. Oatmeal and Edamin ® K were identified to be crucial media components for an efficient production of erinacine C. The highest concentrations of erinacine C were obtained in the optimized culture medium on the 9 th culture day (approximately 260 mg L -1 ). The production of erinacine P was strongly time dependent. The maximum concentration of erinacine P of 184 mg L -1 was observed on the third culture day. Afterwards, the concentrations of erinacine P decreased while the concentrations of erinacine C steadily increased. Comparable results were obtained by HPTLC with UV detection and HPLC with diode-array detection (DAD) analyses. Direct bioautography allowed for an additional analysis of the antimicrobial activity of the secondary metabolites. The C and N sources oatmeal and Edamin ® K induced the formation of erinacine C. Detailed product formation kinetics of the erinacines C and P have been reported for the first time. HPTLC combined with the Aliivibrio fischeri bioassay allowed for an instant detection of cyathane diterpenoids in crude extracts and for an evaluation of the antimicrobial activity of the secondary metabolites directly on the plate.

  19. Research nuclear reactor RA - Annual Report 1996; Istrazivacki nuklearni reaktor RA - Izvestaj za 1996. godinu

    Energy Technology Data Exchange (ETDEWEB)

    Sotic, O [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

    1996-12-01

    Activities related to revitalisation of the RA reactor started in 1986, were continued in 1996. All the planned actions related to renewal of the reactor components were finished. The last, and at the same time most important action, related to exchange of complete reactor instrumentation is underway, delayed. The delivery of components from USSR is late. Production of this instruments is financed by the IAEA according to the contract signed in December 1988 with Russian Atomenergoexport. According to this contract, it has been planned that the RA reactor instrumentation should be delivered to the Vinca Institute by the end of 1990. Only 80% of the instrumentation was delivered until September 1991. Since then any delivery of components to Yugoslavia was stopped because of the temporary embargo imposed by the IAEA. The existing RA reactor instrumentation was dismantled. Control and maintenance of the reactor components was done regularly and efficiently. Fuel inspection by the IAEA safeguards inspectors was done on a monthly basis. There have been on the average 43 employees at the RA reactor which is considered sufficient for maintenance and repair conditions. The problem of financing the reactor activities and maintenance remains unsolved. Research reactor RA Annual report for year 1996 is divided into two main parts to cover: (1) operation and maintenance and (2) activities related to radiation protection. [Serbo-Croat] U toku 1996. godine nastavljeni su poslovi na revitalizaciji reaktora RA, zapocetoj 1986. godine. Okoncan je niz zahvata na opremi postrojenja kojima ce se u narednom periodu omoguciti kontinualan i pouzdan rad ovog reaktora. Poslednji, i ujedno najveci zahvat, koji se odnosi na zamenu celokupne instrumentacije kasni zbog zastoja u isporuci opreme koja se izradjuje u Sovjetskom savezu. Izradu ove opreme finansira Medjunarodna agencija za atomsku energiju kroz ugovor sklopljen decembra 1988. godine sa moskovskom firmom Atomenergoexport. Prema tom

  20. Argonne-Utah studies of 224Ra endosteal surface dosimetry

    International Nuclear Information System (INIS)

    Schlenker, R.A.; Smith, J.M.

    1984-01-01

    The activities of 212 Pb relative to 224 Ra and of 222 Rn relative to 226 Ra were measured in bone surface deposits 24 h after radium injection into beagles. The fractional retention of 220 Rn atoms was measured in vitro with hydrated and dehydrated bone samples to determine the effect of water content on the escape of radon from bone surfaces. The experimental data suggest that substantial 224 Ra daughter product disequilibrium exists in bone surface deposits. Estimates for the lower and upper limits on the fractional retention of 220 Rn in vivo are 0.05 and 0.25, respectively. The average bone surface activity of 212 Pb relative to 224 Ra ranged from 0.34 to 0.71 for four dogs, with the majority of the values toward the low end of the range. Only a small portion of the deposited 212 Pb came from lead in the injection solution despite near equilibrium between 224 Ra and its daughters at the time of injection. The retention data indicate that the endosteal tissue dose rate in the dogs at one day was actually one-third to about one-half that which would be calculated assuming equilibrium of 224 Ra daughter products in bone surface deposits. 11 references, 2 figures, 7 tables

  1. Argonne-Utah studies of 224Ra endosteal surface dosimetry

    International Nuclear Information System (INIS)

    Schlenker, R.A.; Smith, J.M.

    1985-01-01

    The activities of 212 Pb relative to 224 Ra and of 222 Rn relative to 226 Ra were measured in bone surface deposits 24 h after injection of radium into beagles. The fractional retention of 220 Rn atoms was measured in vitro with hydrated and dehydrated bone samples to determine the effect of water content on the escape of radon from bone surfaces. The experimental data suggest that substantial 224 Ra daughter-product disequilibrium exists in bone surface deposits. Estimates for the lower and upper limits on the fractional retention of 220 Rn in vivo are 0.05 and 0.25, respectively. The average bone surface activity of 212 Pb relative to 224 Ra ranged from 0.34 to 0.71 for four dogs, with the majority of the values toward the lower end of the range. Only a small portion of the deposited 212 Pb came from lead in the injection solution despite near equilibrium between 224 Ra and its daughters at the time of injection. The retention data indicate that the endosteal tissue dose rate in the dogs at one day was actually one-third to about one-half that which would be calculated assuming equilibrium of 224 Ra daughter products in bone surface deposits. 11 references, 2 figures, 7 tables

  2. Argonne-Utah studies of 224Ra endosteal surface dosimetry

    International Nuclear Information System (INIS)

    Schlenker, R.A.; Smith, J.M.

    1986-01-01

    The activities of 212 Pb relative to 224 Ra and of 222 Rn relative to 226 Ra were measured in bone surface deposits 24 h after radium injection into beagles. The fractional retention of 220 Rn atoms was measured in vitro with hydrated and dehydrated bone samples to determine the effect of water content on the escape of radon from bone surfaces. The experimental data suggest that substantial 224 Ra daughter product disequilibrium exists in bone surface deposits. Estimates for the lower and upper limits on the fractional retention of 220 Rn in vivo are 0.05 and 0.25, respectively. The average bone surface activity of 212 Pb relative to 224 Ra ranged from 0.34 to 0.71 for four dogs, with the majority of the values toward the low end of the range. Only a small portion of the deposited 212 Pb came from lead in the injection solution despite near equilibrium between 224 Ra and its daughters at the time of injection. The retention data indicate that the endosteal tissue dose rate in the dogs at one day was actually one-third to about one-half that which would be calculated assuming equilibrium of 224 Ra daughter products in bone surface deposits. (orig.)

  3. Determination of natural Ra isotopes in samples from northern Sao Paulo state coastal area

    International Nuclear Information System (INIS)

    Teixeira, Washington Eugenio

    2004-01-01

    The present work aims the determination of natural Ra isotopes in coastal samples collected at Ubatuba region, with the application of the obtained inventories to estimate coastal water mixing rates and assess submarine groundwater discharge. Since these radionuclides are present in sea water in trace form (10''- 16 g/ L), the methodology included pre-concentration of huge volumes of sea water using MnO 2 coated acrylic fiber, leaching of these fibers in HCl media and co-precipitation of the long-lived Ra isotopes with BaSO 4 . Before long-lived radium isotopes determination, the isotopes 223 Ra e 224 Ra were quantified using a delayed coincidence system. The delayed coincidence system utilizes the difference in decay constants of the short-lived Po daughters of radon 219 Rn and 220 Rn to identify alpha particles derived from its decay products. The activities of 226 Ra and 228 Ra were determined by gross alpha and beta counting respectively, of the Ba(Ra)SO 4 precipitate in low-level gas flow proportional detector. Considering the results obtained in 2002 and 2003, the coastal waters exchange time were estimated for Flamengo, Fortaleza and Mar Virado embayments using the activity concentrations of 223 Ra, 224 Ra, 226 Ra and 228 Ra. (author)

  4. Abscisic Acid Induced Changes in Production of Primary and Secondary Metabolites, Photosynthetic Capacity, Antioxidant Capability, Antioxidant Enzymes and Lipoxygenase Inhibitory Activity of Orthosiphon stamineus Benth.

    Directory of Open Access Journals (Sweden)

    Mohd Hafiz Ibrahim

    2013-07-01

    Full Text Available An experiment was conducted to investigate and distinguish the relationships in the production of total phenolics, total flavonoids, soluble sugars, H2O2, O2−, phenylalanine ammonia lyase (PAL activity, leaf gas exchange, antioxidant activity, antioxidant enzyme activity [ascorbate peroxidase (APX, catalase (CAT, superoxide dismutase (SOD and Lipoxygenase inhibitory activity (LOX] under four levels of foliar abscisic acid (ABA application (0, 2, 4, 6 µM for 15 weeks in Orthosiphon stamineus Benth. It was found that the production of plant secondary metabolites, soluble sugars, antioxidant activity, PAL activity and LOX inhibitory activity was influenced by foliar application of ABA. As the concentration of ABA was increased from 0 to 6 µM the production of total phenolics, flavonoids, sucrose, H2O2, O2−, PAL activity and LOX inhibitory activity was enhanced. It was also observed that the antioxidant capabilities (DPPH and ORAC were increased. This was followed by increases in production of antioxidant enzymes APX, CAT and SOD. Under high application rates of ABA the net photosynthesis and stomatal conductance was found to be reduced. The production of primary and secondary metabolites displayed a significant positive relationship with H2O2 (total phenolics, r2 = 0.877; total flavonoids, r2 = 0.812; p ≤ 0.05 and O2− (total phenolics, r2 = 0.778; total flavonoids, r2 = 0.912; p ≤ 0.05. This indicated that increased oxidative stress at high application rates of ABA, improved the production of phytochemicals.

  5. Methylated polycyclic aromatic hydrocarbons and/or their metabolites are important contributors to the overall estrogenic activity of polycyclic aromatic hydrocarbon-contaminated soils.

    Science.gov (United States)

    Lam, Monika M; Engwall, Magnus; Denison, Michael S; Larsson, Maria

    2018-02-01

    In the present study 42 polycyclic aromatic compounds (PACs) were investigated for their estrogenic potential using the VM7Luc4E2 transactivation assay. Relative potencies were determined for mass-balance analysis. In addition, compounds were tested in combination with the estrogen receptor (ER) antagonist ICI182,780 (ICI) and the aryl hydrocarbon receptor antagonist/CYP1A1 inhibitor α-naphthoflavone. Luciferase induction and CYP1A1-dependent ethoxyresorufin-O-deethylase (EROD) activity were measured to assess whether the estrogenic activity was elicited by the compound itself and/or by its metabolites. Relative potencies ranged between 10 -7 and 10 -4 . The ability of ICI to decrease luciferase activity stimulated by all compounds indicated that the induction responses were ER-dependent. The aryl hydrocarbon receptor antagonist/CYP1A1 inhibitor α-naphthoflavone decreased luciferase induction and EROD activity by several compounds, including the methylated chrysenes, suggesting that metabolites of these chemicals contributed to ER activation. Several PACs, such as acridine and its derivatives, appear to directly activate the ER. Furthermore, extracts of soils from industrial areas were examined using this bioassay, and estrogenic activity was detected in all soil samples. Mass-balance analysis using a combination of relative potencies and chemical analysis of the samples suggested that polycyclic aromatic hydrocarbons (PAHs) and alkylated PAHs, such as 1- and 3-methylchrysene, are important contributors to the overall estrogenic activity. However, these results revealed that a considerable proportion of the estrogenic activity in the soil remained unexplained, indicating the presence of other significant estrogenic compounds. Environ Toxicol Chem 2018;37:385-397. © 2017 SETAC. © 2017 SETAC.

  6. Radiochemical determination and separation or total radium, 226Ra and 224Ra; Analisis Radioquimico de Radio total, Radio-226 y Radio-224

    Energy Technology Data Exchange (ETDEWEB)

    Suarez, J A; Gonzalez, J A; Pablo, M A. de

    1987-07-01

    Radiochemical purification and separation of radium has been carried out and the determination of total radium solubilized in aqueous samples has been studied assuming that all the alpha emitters of the sample have their origin in the 226Ra and elements of its desintegration chain. Also, the activities of 22Ra and 226 Ra have been evaluated separately doing a measurement after the chemical separation of the radium and another one 10 days after. (Author) 9 refs.

  7. Functional characterization of the 1,5-benzodiazepine clobazam and its major active metabolite N-desmethylclobazam at human GABAA receptors expressed in Xenopus laevis oocytes

    DEFF Research Database (Denmark)

    Hammer, Harriet; Ebert, Bjarke; Jensen, Henrik S.

    2015-01-01

    different in vivo adverse effects and addiction liability profile than the classic 1,4-benzodiazepines. In this study, it was investigated whether the in vitro pharmacological properties of clobazam and its major active metabolite N-desmethylclobazam could explain some of these clinical differences...... by the 1,4-benzodiazepine clonazepam. All three compounds potentiated GABA EC20-evoked responses through the α1,2,3,5β2γ2S GABAARs in a reversible and concentration-dependent manner, with each displaying similar EC50 values at the four subtypes. Furthermore, the degrees of potentiation of the GABA EC20...

  8. Chemical dosimetry at the RA reactor; Hemijska dozimetrija reaktora RA

    Energy Technology Data Exchange (ETDEWEB)

    Gal, O [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

    1961-12-15

    This report presents the results of measurements of absorbed doses axial and radial distribution in the vertical experimental channels of the RA reactor. Measurements were done in channels VK-5, VK-7, VK-9 and GF-36. Results were compared to the results of calorimetry measurements and measured neutron flux values performed by other laboratories. Fricke and oxalate dosemeters were used in addition to the cobalt indicators.

  9. Doses from 222Rn, 226Ra, and 228Ra in groundwater from Guarani aquifer, South America.

    Science.gov (United States)

    Bonotto, D M

    2004-01-01

    Groundwater samples were analysed for 222Rn, 226Ra, and 228Ra in Guarani aquifer spreading around 1 million km2 within four countries in South America, and it was found that their activity concentrations are lognormally distributed. Population-weighted average activity concentration for these radionuclides allowed to estimate a value either slightly higher (0.13 mSv/year) than 0.1 mSv for the total effective dose or two times higher (0.21 mSv/year) than this limit, depending on the choice of the dose conversion factor. Such calculation adds useful information for the appropriate management of this transboundary aquifer that is socially and economically very important to about 15 million inhabitants living in Brazil, Argentina, Uruguay and Paraguay.

  10. Doses from 222Rn, 226Ra, and 228Ra in groundwater from Guarani aquifer, South America

    International Nuclear Information System (INIS)

    Bonotto, D.M.

    2004-01-01

    Groundwater samples were analysed for 222 Rn, 226 Ra, and 228 Ra in Guarani aquifer spreading around 1 million km 2 within four countries in South America, and it was found that their activity concentrations are lognormally distributed. Population-weighted average activity concentration for these radionuclides allowed to estimate a value either slightly higher (0.13 mSv/year) than 0.1 mSv for the total effective dose or two times higher (0.21 mSv/year) than this limit, depending on the choice of the dose conversion factor. Such calculation adds useful information for the appropriate management of this transboundary aquifer that is socially and economically very important to about 15 million inhabitants living in Brazil, Argentina, Uruguay and Paraguay

  11. Possibilities for power reactor structural material and fuel testing in reactor RA; Mogucnosti reaktora RA za testiranje konstrukcionih materijala i goriva energetskih reaktora

    Energy Technology Data Exchange (ETDEWEB)

    Martinc, R; Lazarevic, Dj; Stefanovic, D; Cupac, S; Pesic, M [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

    1978-05-15

    Nuclear reactor RA at Vinca has been designed as a high flux general purpose research reactor. Among other it was intended to play a role of material testing reactor. A scope of activities of Material Laboratory and Reactor RA Department of Boris Kidric Institute is presented in this report. Reactor RA capacity for reactor structural material and fuel irradiation is also described. The increase of RA reactor irradiation capacity is based on the improvement of VISA type fuel channel for fast neutron irradiations, as well as on the general neutron flux increase, due to introduction of highly enriched uranium fuel into reactor core and the advanced in-core fuel management. The irradiation capacities described allow for the reactor material and fuel testing to the considerable extent. Istrazivacki reaktor RA u Vinci je projektovan kao visokofluksni istrazivacki reaktor opste namene. Pored ostalog, on je namenjen i za testiranje reaktorskih konstrukcionih materijala i goriva. U radu je dat pregled aktivnosti Laboratorije za materijale IBK i reaktora RA na tom podrucju, kao i opis povecanih mogucnosti reaktora RA za ozracivanje reaktorskih materijala i goriva u cilju njihovog testiranja. Povecanje mogucnosti reaktora RA zasniva se na usavrsavanju specijalnog gorivnog kanala tipa VISA (za ozracivanje materijala brzim neutronima), kao i na opstem povecanju neutronskog fluksa na osnovu uvodjenja i nacina koriscenja visokoobogacenog uranskog goriva u reaktoru RA. Opisane mogucnosti reaktora RA dozvoljavaju u znatnoj meri ispitivanje konstrukcionih materijala i goriva energetskih reaktora.

  12. Research nuclear reactor RA - Annual Report 1994; Istrazivacki nuklearni reaktor RA - Izvestaj za 1994. godinu

    Energy Technology Data Exchange (ETDEWEB)

    Sotic, O [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

    1994-12-01

    Activities related to revitalisation of the RA reactor stared in 1986, were continued in 1991. A number of interventions on the reactor components were finished that are supposed to enable continuous and reliable operation. The last, and at the same time largest action, related to exchange of complete reactor instrumentation is underway, but it is behind the schedule in 1991 because the delivery of components from USSR is late. Production of this instruments is financed by the IAEA according to the contract signed in December 1988 with Russian Atomenergoexport. According to this contract, it has been planned that the RA reactor instrumentation should be delivered to the Vinca Institute by the end of 1990. Only 56% of the instrumentation was delivered until September 1991. Since then any delivery of components to Yugoslavia was stopped because of the temporary embargo imposed by the IAEA. In 1991 most of the existing RA reactor instrumentation was dismantled, only the part needed for basic measurements when reactor is not operated, was maintained. Activities related to improvement of Russian project were continued in 1994. Control and maintenance of the reactor components was done regularly and efficiently. Extensive repair of the secondary coolant loop is almost finished and will be completed in the first part of 1995 according to existing legal procedures and IAEA recommendations. Fuel inspection by the IAEA safeguards inspectors was done on a monthly basis. There have been on the average 47 employees at the RA reactor which is considered sufficient for maintenance and repair conditions. Research reactor RA Annual report for year 1991 is divided into two main parts to cover: (1) operation and maintenance and (2) activities related to radiation protection. [Serbo-Croat] U 1994. godini nastavljeni su poslovi na revitalizaciji reaktora RA, zapocetoj 1986. godine. Okoncan je niz zahvata na opremi postrojenja kojima ce se u narednom periodu omoguciti kontinualan i

  13. RA Reactor applications, Annex A

    International Nuclear Information System (INIS)

    Cupac, S.; Vukadin, Z.

    2000-01-01

    Full text: In 2000 Ra reactor was not operated. New instrumentation is not complete, without it, it is not possible to think about reactor start-up. Since 1985, when reactor operation was forbidden, there are 480 fuel elements left in 48 fuel channels in the reactor core. Heavy water was removed from the reactor core because of the repair of the heavy water pumps in 1986. The old instrumentation was removed. Eleven years after being left to its own destiny, it would be difficult to imagine that anybody would think of reactor restart without examining the state of reactor vessel and other vital reactor components. Maintaining the reactor under existing conditions without final decision about restart or permanent shutdown is destructive for this nuclear facility. The existing state that pertains for more than 10 years would have only one result, destruction of the RA reactor [sr

  14. RA Reactor applications, Annex A

    International Nuclear Information System (INIS)

    Cupac, S.; Vukadin, Z.

    1998-01-01

    Full text: In 1998 Ra reactor was not operated. New instrumentation is not complete, without it, it is not possible to think about reactor start-up. Since 1985, when reactor operation was forbidden, there are 480 fuel elements left in 48 fuel channels in the reactor core. Heavy water was removed from the reactor core because of the repair of the heavy water pumps in 1986. The old instrumentation was removed. Eleven years after being left to its own destiny, it would be difficult to imagine that anybody would think of reactor restart without examining the state of reactor vessel and other vital reactor components. Maintaining the reactor under existing conditions without final decision about restart or permanent shutdown is destructive for this nuclear facility. The existing state that pertains for more than 10 years would have only one result, destruction of the RA reactor [sr

  15. RA Reactor applications, Annex A

    International Nuclear Information System (INIS)

    Cupac, S.; Vukadin, Z.

    1996-01-01

    Full text: In 2000 Ra reactor was not operated. New instrumentation is not complete, without it, it is not possible to think about reactor start-up. Since 1985, when reactor operation was forbidden, there are 480 fuel elements left in 48 fuel channels in the reactor core. Heavy water was removed from the reactor core because of the repair of the heavy water pumps in 1986. The old instrumentation was removed. Eleven years after being left to its own destiny, it would be difficult to imagine that anybody would think of reactor restart without examining the state of reactor vessel and other vital reactor components. Maintaining the reactor under existing conditions without final decision about restart or permanent shutdown is destructive for this nuclear facility. The existing state that pertains for more than 10 years would have only one result, destruction of the RA reactor [sr

  16. 226Ra bioavailability of plants at urgeirica uranium mill tailings

    International Nuclear Information System (INIS)

    Madruga, M.J.; Brogueira, A.

    2002-01-01

    Large amounts of solid wastes (tailings) resulting from the exploitation and treatment of uranium ore at the Urgeirica mine (north of Portugal) have been accumulated in dams (tailing ponds). To reduce the dispersion of natural radionuclides into the environment some dams were revegetated with eucalyptus (Eucalyptus globolus) and pines (Pinus pinea). Besides, some shrubs (Cytisus s.p.) are growing at some of the dams. The objective of this study is to determine the 226 Ra bioavailability from uranium mill tailings through the quantification of the total and available fraction of radium in the solid wastes and to estimate its transfer to the plants growing on the tailing piles. Plants and solid waste samples were randomly collected at dams. Activity concentration of 226 Ra in plants (aerial part and roots) and solid wastes were measured by gamma spectrometry. The exchangeable fraction of radium in solid wastes was quantified using one single step extraction with 1 mol dm -3 ammonium acetate (pH=7) or 1 mol dm -3 calcium chloride solutions. The results obtained for the 226 Ra uptake by plants show that 226 Ra concentration ratios for eucalyptus and pines decrease at low 226 Ra concentration in the solid wastes and appear relatively constant at higher radium concentrations. For shrubs, the concentration ratios increase at higher 226 Ra solid waste concentrations approaching a saturation value. Percentage values of 16.0±8.3 and 12.9±8.9, for the fraction of radium extracted from the solid wastes, using 1 mol dm -3 ammonium acetate or calcium chloride solutions respectively, were obtained. The 226 Ra concentration ratios determined on the basis of exchangeable radium are one order of magnitude higher than those based on total radium. It can be concluded that, within the standard error values, more consistent 226 Ra concentration ratios were obtained when calculated on the basis of available radium than when total radium was considered, for all the dams. (author)

  17. 226Ra chronology of a coastal marine sediment

    International Nuclear Information System (INIS)

    Koide, M.; Bruland, K.; Goldberg, E.D.

    1976-01-01

    Unsupported 226 Ra (tsub (1/2) = 1620 years) in marine sediments can provide a basis for measuring rates of accumulation of the order of centimeters per thousand years. The excess radium apparently enters the sediments incorporated in phytoplankton. The sensitivity of the method depends upon the initial value of the unsupported 226 Ra and of the value of 230 Th, a parent of 226 Ra, in the sedimentary components. 226 Ra dating was applied to a sediment taken from the slope of the San Clemente Basin in the Southern California coastal region. Rates of sedimentation over two half-lives of the nuclide were found to be either 5.2 or 5.3 cm/1000 years depending upon which of two models for the geochronology is used. One model assumes that the 230 Th brings to the deposit an amount of 226 Ra in equilibrium with it. The other is based upon the growth of the 226 Ra from the 230 Th in the sedimentary components. 238+239 Pu and 210 Pb levels in the upper strata indicated sedimentation rates of the order of 100-500 cm/1000 years, i.e. much faster accumulations. It is suggested that these derived rates are spurious and reflect bioturbative activities of surface-living organisms. (Auth.)

  18. Lightcurve of NEA 1993 RA

    Science.gov (United States)

    Vaduvescu, Ovidiu; Aznar Macias, Amadeo

    2018-01-01

    The near-Earth asteroid (NEA) 1993 RA was observed with the 2.5-m Isaac Newton Telescope (INT) in full Moon conditions for 8h total during three successive nights (2017 Oct 3-6). The composite lightcurve could be fit by a 3-order period P = 5.64 ± 0.01 h with amplitude of 0.13 mag; other solutions are possible.

  19. Regulations for RA reactor operation

    International Nuclear Information System (INIS)

    1980-09-01

    Regulations for RA reactor operation are written in accordance with the legal regulations defined by the Law about radiation protection and related legal acts, as well as technical standards according to the IAEA recommendations. The contents of this book include: fundamental data about the reactor; legal regulations for reactor operation; organizational scheme for reactor operation; general and detailed instructions for operation, behaviour in the reactor building, performing experiments; operating rules for operation under steady state and accidental conditions [sr

  20. An evaluation of the worker exposure during the RA reactor decommissioning due to presence of contamination

    International Nuclear Information System (INIS)

    Ljubenov, V.; Simovic, R.

    2005-01-01

    In this paper a possibility to establish the relationship between the presence of the surface contamination in the RA reactor rooms and the worker exposure during the decommissioning activities is discussed. RESRAD-BUILD code and the models typical for the RA reactor has been used to determine annual doses from the supposed activities of the main expected RA reactor contaminants. Different room air exchange rates have been modelled and analysed. (author) [sr

  1. Production of Ra225 precursor for Ac225/Bi213 generators. Final CRADA Report

    International Nuclear Information System (INIS)

    Ehst, D.A.

    2009-01-01

    Russian subcontractors shipped two small deliveries of Ra225 to PNNL for evaluation. The activity was close to the requisite amount in the subcontract. The first labeled properly; the second did not. This showed that the Russians could supply Ra225 to the US; however they proved unable to meet future demands for larger amounts of activity. The US DOE attempts to get Ra225 from Russian should be terminated; the Russians, under Rosatom, are not interested in this business.

  2. RA Reactor operation and maintenance (I-IX), part VII, Task 3.08/04, Refurbishment of the RA reactor; Pogon i odrzavanje reaktora (I-IX), VII Deo, Zadatak 3.08/04 Remont reaktora RA

    Energy Technology Data Exchange (ETDEWEB)

    Zecevic, V [Institute of Nuclear Sciences Boris Kidric, Reaktor RA, Vinca, Beograd (Serbia and Montenegro)

    1963-12-15

    This volume covers the following reports concerned with the maintenance and repair work of the RA reactor: repair of the technical water system; maintenance of the transportation equipment; vacuuming and drying during refurbishment; repair and decontamination of the distillation device; and the report on participation of the operational dosimetry division in the RA reactor refurbishment activities.

  3. Report on the activity of the RA reactor operation for the period from July 1 1961 - Sept. 30 1961; Tromesecni izvestaj za period od 1.VII do 30.IX 1961. g

    Energy Technology Data Exchange (ETDEWEB)

    Zecevic, V [Laboratorija za eksploataciju reaktora RA, Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

    1961-09-15

    During the reporting period the reactor was permanently ready for operation and responding to the demands of the experimenters. The reactor was operating for 408.5 hours at power levels from 50 - 5000 kW, or 1985 MWh in total, burnup of the first batch of fuel was 22.55%. Reactor core was made of 56 fuel channels. Activities related to construction of new and improvement of the existing equipment was continued in order to enable safe operation and successful utilization of the RA reactor. Exchange of the electronic tubes was continued in order to increase the stability of the reactor control and reactor protection systems. About 65% of tubes planned to be exchanged this year was done. Cooperation with the CEN Saclay, France related to construction of experimental loops VISA-1 and VISA-2 was continued as well as cooperation with Poland concerned with exchange of experts. The problem of lack of properly trained staff was nor solved. [Serbo-Croat] U izvestajnom periodu reaktor je uvek bio spreman za rad i odgovarao je zahtevima eksperimentatora. Reaktor je radio 408,5 casova na snagama od 50-5000 kW, odnosno ukupno 1985 MWh, pri cemu je ukupan utrosak prve sarze goriva bio 22,55%. Jezgro reaktora bilo je sacinjeno od 56 tehnoloskih kanala. Radi bezbednijeg pogona i sto uspesnije eksploatacije reaktora RA nastavljeno je sa radovima na realizaciji novih i poboljsanju postojecih uredjaja. U cilju povecanja stabilnosti elektronskih instrumenta u sistemu upravljanja i zastiti reaktora nastavljeno je sa zamenom elektronskih cevi, do sada je zamenjeno oko 65% radova predvidjenih za ovu godinu. Nastavljena je saradnja sa nuklearnim centrom u Saclay, Francuska na izradi petlje VISA-1 i VISA-2 i saradnja sa Poljskom u razmeni strucnjaka. Problem nedostatka kadrova nije resen.

  4. Comparison of the in vivo and in vitro activities of adenylate cyclase from Mycobacterium tuberculosis H37Ra(NCTC 7417)

    International Nuclear Information System (INIS)

    Padh, Harish; Venkitsubramanian, T.A.

    1979-01-01

    The incorporation of [ 14 C] adenine into the adenosine 3', 5'-monophosphate (cyclic AMP) fraction by whole cells of Mycobacterium tuberculosis was taken as a measure of the in vivo activity of adenylate cyclase. The in vivo activity of adenylate cyclase was significantly inhibited by glucose, thus suggesting that the low level of cyclic AMP in the presence of glucose is due to the inhibited synthesis of cyclic AMP. In vitro activity of adenylate cyclase had optimum pH of 8.5 and Km of 1.33 mM for ATP. Glucose and other sugars did not show significant inhibition of in vitro activity. The results suggest that the adenylate cyclase activity becomes less sensitive to glucose when the bacterial cells are disrupted, an analogy with eukaryotic adenylate cyclase which loses sensitivity to hormones when the cells are disrupted. (auth.)

  5. Concentrations, patterns and metabolites of organochlorine pesticides in relation to xenobiotic phase I and II enzyme activities in ringed seals (Phoca hispida) from Svalbard and the Baltic Sea

    International Nuclear Information System (INIS)

    Routti, Heli; Bavel, Bert van; Letcher, Robert J.; Arukwe, Augustine; Chu Shaogang; Gabrielsen, Geir W.

    2009-01-01

    The present study investigates the concentrations and patterns of organochlorine pesticides (OCPs) and their metabolites in liver and plasma of two ringed seal populations (Phoca hispida): lower contaminated Svalbard population and more contaminated Baltic Sea population. Among OCPs, p,p'-DDE and sum-chlordanes were the highest in concentration. With increasing hepatic contaminant concentrations and activities of xenobiotic-metabolizing enzymes, the concentrations of 3-methylsulfonyl-p,p'-DDE and the concentration ratios of pentachlorophenol/hexachlorobenzene increased, and the toxaphene pattern shifted more towards persistent Parlar-26 and -50 and less towards more biodegradable Parlar-44. Relative concentrations of the chlordane metabolites, oxychlordane and -heptachlorepoxide, to sum-chlordanes were higher in the seals from Svalbard compared to the seals from the Baltic, while the trend was opposite for cis- and trans-nonachlor. The observed differences in the OCP patterns in the seals from the two populations are probably related to the catalytic activity of xenobiotic-metabolizing enzymes, and also to differences in dietary exposure. - Contrasting patterns of organochlorine pesticides in two ringed seal populations.

  6. Concentrations, patterns and metabolites of organochlorine pesticides in relation to xenobiotic phase I and II enzyme activities in ringed seals (Phoca hispida) from Svalbard and the Baltic Sea

    Energy Technology Data Exchange (ETDEWEB)

    Routti, Heli, E-mail: heli.routti@npolar.n [Norwegian Polar Institute, Polar Environmental Centre, 9296 Tromso (Norway); Centre of Excellence in Evolutionary Genetics and Physiology, Department of Biology, University of Turku, 20014 Turku (Finland); Bavel, Bert van [MTM Research Centre, Orebro University, 70182 Orebro (Sweden); Letcher, Robert J. [Wildlife Toxicology and Disease Program, Wildlife and Landscape Science Directorate, Science and Technology Branch, Environment Canada, National Wildlife Research Centre, Carleton University, Ottawa, Ontario K1A 0H3 (Canada); Arukwe, Augustine [Department of Biology, Norwegian University of Science and Technology, 7491 Trondheim (Norway); Chu Shaogang [Wildlife Toxicology and Disease Program, Wildlife and Landscape Science Directorate, Science and Technology Branch, Environment Canada, National Wildlife Research Centre, Carleton University, Ottawa, Ontario K1A 0H3 (Canada); Gabrielsen, Geir W. [Norwegian Polar Institute, Polar Environmental Centre, 9296 Tromso (Norway)

    2009-08-15

    The present study investigates the concentrations and patterns of organochlorine pesticides (OCPs) and their metabolites in liver and plasma of two ringed seal populations (Phoca hispida): lower contaminated Svalbard population and more contaminated Baltic Sea population. Among OCPs, p,p'-DDE and sum-chlordanes were the highest in concentration. With increasing hepatic contaminant concentrations and activities of xenobiotic-metabolizing enzymes, the concentrations of 3-methylsulfonyl-p,p'-DDE and the concentration ratios of pentachlorophenol/hexachlorobenzene increased, and the toxaphene pattern shifted more towards persistent Parlar-26 and -50 and less towards more biodegradable Parlar-44. Relative concentrations of the chlordane metabolites, oxychlordane and -heptachlorepoxide, to sum-chlordanes were higher in the seals from Svalbard compared to the seals from the Baltic, while the trend was opposite for cis- and trans-nonachlor. The observed differences in the OCP patterns in the seals from the two populations are probably related to the catalytic activity of xenobiotic-metabolizing enzymes, and also to differences in dietary exposure. - Contrasting patterns of organochlorine pesticides in two ringed seal populations.

  7. RA Research reactor, Part 1, Operation and maintenance of the RA nuclear reactor for 1986

    International Nuclear Information System (INIS)

    Sotic, O.; Martinc, R.; Cupac, S.; Sulem, B.; Badrljica, R.; Majstorovic, D.; Sanovic, V.

    1986-01-01

    In order to enable future reliable operation of the RA reactor, according to new licensing regulations, three major tasks started in 1984 were fulfilled: building of the new emergency system, reconstruction of the existing ventilation system, and reconstruction of the power supply system. Simultaneously in 1985/1986 renewal of the instrumentation and reconstruction of the system for handling and storage of the spent fuel in the reactor building have started. Design projects for these tasks are almost finished and the reconstruction of both systems is expected to be finished until 1988 and mid 1989 respectively. RA reactor Safety report was finished according to the recommendations of the IAEA. Investments in 1986 were used for 8000 kg of heavy water, maintenance of reactor systems and supply of new components, reconstruction of reactor systems. This report includes 8 annexes concerning reactor operation, activities of services and financial issues [sr

  8. Rheinanthrone, a metabolite of sennoside A, triggers macrophage activation to decrease aquaporin-3 expression in the colon, causing the laxative effect of rhubarb extract.

    Science.gov (United States)

    Kon, Risako; Ikarashi, Nobutomo; Nagoya, Chika; Takayama, Tomoko; Kusunoki, Yoshiki; Ishii, Makoto; Ueda, Harumi; Ochiai, Wataru; Machida, Yoshiaki; Sugita, Kazuyuki; Sugiyama, Kiyoshi

    2014-02-27

    Aquaporin-3 (AQP3) is expressed in mucosal epithelial cells in the colon and is important for regulating fecal water content. We examined the role of AQP3 in the laxative effect of rhubarb extract. After orally administering rhubarb extract or its major component (sennoside A) to rats, the fecal water content, AQP3 expression and prostaglandin E2 (PGE2) concentrations in the colon were examined. The mechanism by which sennoside A decreases the expression of AQP3 was examined using the human colon cancer HT-29 cells and macrophage-derived Raw264.7 cells. During diarrhea by rhubarb extract administration, the PGE2 levels in the colon increased while the AQP3 expression significantly decreased. Similar changes were also observed when sennoside A was administered. When sennoside A or its metabolites, rheinanthrone and rhein were added to Raw264.7 cells, a significant increase in the PGE2 concentration was observed only in cells treated with rheinanthrone. Fifteen minutes after adding PGE2 to the HT-29 cells, the AQP3 expression decreased to approximately 40% of the control. When pretreated with indomethacin, sennoside A neither decreased the AQP3 expression nor induced diarrhea. Sennoside A may decrease AQP3 expression in the colon to inhibit water transport from the luminal to the vascular side, leading to a laxative effect. The decreases in the levels of AQP3 are caused by rheinanthrone, which is a metabolite of sennoside A, this metabolite activates the macrophages in the colon and increases the secretion of PGE2; PGE2 acts as a paracrine factor and decreases AQP3 expression in colon mucosal epithelial cells. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Determination of 226Ra and 224Ra in sediments samples by liquid scintillation counting

    International Nuclear Information System (INIS)

    Villa, M.; Moreno, H.P.; Manjon, G.

    2005-01-01

    An experimental procedure has been developed for a rapid determination of the activity concentration of 226 Ra and 224 Ra in sediments by liquid scintillation counting. The importance of the method lies in its application to the measurement of sediments where the Ra-isotopes activity concentration has been increased due to an anthropomorphic enhancement based on releases of naturally occurring radioactive material (NORM). A sample pre-treatment, including a digestion with aqua regia and a precipitation of hydroxides, was applied to samples before the radium extraction, which was made by co-precipitation with barium. Measurements were done in a low background scintillation spectrometer Quantulus 1220, which can separate and detect simultaneously α and β particles. Additionally, some improvements are suggested for a better α and β interference correction of the results. The obtaining of radiochemical yields is also improved using 133 Ba as tracer, which decays by emission of conversion electrons and γ-rays; the wide range of radiochemical yields obtained confirms the need of this analyses. The procedure has been applied to the measurement of riverbed sediments from an estuary in the south-west of Spain, affected in the past by direct and indirect phosphogypsum discharges

  10. Potential antiproliferative activity of polyphenol metabolites against human breast cancer cells and their urine excretion pattern in healthy subjects following acute intake of a polyphenol-rich juice of grumixama (Eugenia brasiliensis Lam.).

    Science.gov (United States)

    Teixeira, L L; Costa, G R; Dörr, F A; Ong, T P; Pinto, E; Lajolo, F M; Hassimotto, N M A

    2017-06-21

    The bioavailability and metabolism of anthocyanins and ellagitannins following acute intake of grumixama fruit, native Brazilian cherry, by humans, and its in vitro antiproliferative activity against breast cancer cells (MDA-MB-231) were investigated. A single dose of grumixama juice was administered to healthy women (n = 10) and polyphenol metabolites were analyzed in urine and plasma samples collected over 24 h. The majority of the metabolites circulating and excreted in urine were phenolic acids and urolithin conjugates, the gut microbiota catabolites of both classes of polyphenols, respectively. According to pharmacokinetic parameters, the subjects were divided into two distinct groups, high and low urinary metabolite excretors. The pool of polyphenol metabolites found in urine samples showed a significant inhibition of cell proliferation and G2/M cell cycle arrest in MDA-MB-231 cells. Our findings demonstrate the large interindividual variability concerning the polyphenol metabolism, which possibly could reflect in health promotion.

  11. Research nuclear reactor RA - Annual report 1992

    International Nuclear Information System (INIS)

    Sotic, O.

    1992-12-01

    Research reactor RA Annual report for year 1992 is divided into two main parts to cover: (1) operation and maintenance and (2) activities related to radiation protection. First part includes 8 annexes describing reactor operation, activities of services for maintenance of reactor components and instrumentation, financial report and staffing. Second annex B is a paper by Z. Vukadin 'Recurrence formulas for evaluating expansion series of depletion functions' published in 'Kerntechnik' 56, (1991) No.6 (INIS record no. 23024136. Second part of the report is devoted to radiation protection issues and contains 4 annexes with data about radiation control of the working environment and reactor environment, description of decontamination activities, collection of radioactive wastes, and meteorology data [sr

  12. Kazan period of life-sustaining activity of professor V.I. Ra-zumovsky — a pioneer of Russian neurosurgery

    Directory of Open Access Journals (Sweden)

    Danilov V.I.

    2012-06-01

    Full Text Available There were presented historical data of life-sustaining activity of professor V. I. Razumovsky — a pioneer of Russian neurosurgery, who began to perform and then was performing systematically neurosurgical operations in the Kazan clinic under the guidance of outstanding neurologists V. M. Bekhterev and L. O. Darkshevich.

  13. RA reactor building and installations; Zgrada 'RA' i instalacije

    Energy Technology Data Exchange (ETDEWEB)

    Badrljica, R; Sanovic, V; Skoric, M [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

    1985-08-15

    RA reactor building is made of reinforced concrete and bricks. It is closed facility with a limited number of controlled openings, doors and windows. The site of the building is 100 m above the sea level, 20 m above the mean Danube level and 8 m above the level of the neighbouring stream Mlaka. The building consists of three parts: central prismatic part, annex - surrounding the central part and the sanitary corridor. The biggest space is the reactor hall. In addition to the detailed description and drawings of the reactor building this documents includes design specifications of: electrical installation, water supply system, sewage system, ventilation and heating, gas and compressed air systems. A separate chapter is devoted to fire protection. Zgrada reaktora RA izgradjena je od armiranog betona i opeke, kao zatvoreni objekat ogranicenog broja kontolisanih otvora, sa ogranicenim brojem vrata i prozora. Plato na kojem je zgrada izgradjena nalazi se na 100 m nadmorske visine, na 20 m iznad srednjeg vodostaja Dunava i 8 m iznad nivoa obliznjeg potoka Mlaka. Zgrada se sastoji iz tri dela: sredisnjeg prizmaticnog dela, aneksa - prstenastog okvira sredisnog dela i sanitarnog propusnika. Pojedinacno najveci prostor zauzima reaktorska hala. Pored detaljnog opisa i plana zgrade, ovaj dokument sadrzi projekat elektricne instalacije, projekat vodovoda i kanalizacije, ventilacije i grejanja, instalacije gasa i komprimovanog vazduha. Posebno poglavlje posveceno je protivpozarnoj zastiti.

  14. Metabolite Profiling of the Microalgal Diatom Chaetoceros Calcitrans and Correlation with Antioxidant and Nitric Oxide Inhibitory Activities via 1H NMR-Based Metabolomics

    Directory of Open Access Journals (Sweden)

    Awanis Azizan

    2018-05-01

    Full Text Available Microalgae are promising candidate resources from marine ecology for health-improving effects. Metabolite profiling of the microalgal diatom, Chaetoceros calcitrans was conducted by using robust metabolomics tools, namely 1H nuclear magnetic resonance (NMR spectroscopy coupled with multivariate data analysis (MVDA. The unsupervised data analysis, using principal component analysis (PCA, resolved the five types of extracts made by solvents ranging from polar to non-polar into five different clusters. Collectively, with various extraction solvents, 11 amino acids, cholesterol, 6 fatty acids, 2 sugars, 1 osmolyte, 6 carotenoids and 2 chlorophyll pigments were identified. The fatty acids and both carotenoid pigments as well as chlorophyll, were observed in the extracts made from medium polar (acetone, chloroform and non-polar (hexane solvents. It is suggested that the compounds were the characteristic markers that influenced the separation between the clusters. Based on partial least square (PLS analysis, fucoxanthin, astaxanthin, violaxanthin, zeaxanthin, canthaxanthin, and lutein displayed strong correlation to 2,2-diphenyl-1-picrylhydrazyl (DPPH free radical scavenging and nitric oxide (NO inhibitory activity. This metabolomics study showed that solvent extractions are one of the main bottlenecks for the maximum recovery of bioactive microalgal compounds and could be a better source of natural antioxidants due to a high value of metabolites.

  15. Simultaneous determination of sibutramine and its active metabolites in human plasma by LC-MS/MS and its application to a pharmacokinetic study.

    Science.gov (United States)

    Bae, Jung-Woo; Choi, Chang-Ik; Jang, Choon-Gon; Lee, Seok-Yong

    2011-11-01

    A simple and sensitive liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) technique was developed and validated for the determination of sibutramine and its N-desmethyl metabolites (M1 and M2) in human plasma. After extraction with methyl t-butyl ether, chromatographic separation of analytes in human plasma was performed using a reverse-phase Luna C18 column with a mobile phase of acetonitrile-10 mm ammonium formate buffer (50:50, v/v) and quantified by ESI-MS/MS detection in positive ion mode. The flow rate of the mobile phase was 200 μL/min and the retention times of sibutramine, M1, M2 and internal standard (chlorpheniramine) were 1.5, 1.4, 1.3 and 0.9 min, respectively. The calibration curves were linear over the range 0.05-20 ng/mL, for sibutramine, M1 and M2. The lower limit of quantification was 0.05 ng/mL using 500 μL of human plasma. The mean accuracy and the precision in the intra- and inter-day validation for sibutramine, M1 and M2 were acceptable. This LC-MS/MS method showed improved sensitivity and a short run time for the quantification of sibutramine and its two active metabolites in plasma. The validated method was successfully applied to a pharmacokinetic study in human. Copyright © 2011 John Wiley & Sons, Ltd.

  16. Behavioral and electroencephalographic evaluation of the anticonvulsive activity of Moringa oleifera leaf non-polar extracts and one metabolite in PTZ-induced seizures.

    Science.gov (United States)

    González-Trujano, María Eva; Martínez-González, Claudia Lizbeth; Flores-Carrillo, Maricela; Luna-Nophal, Sara Ibeth; Contreras-Murillo, Gerardo; Magdaleno-Madrigal, Víctor Manuel

    2018-01-15

    Moringa oleifera Lamarck is a species that has long been used in high demand in folk medicine, including for the treatment of epilepsy. Nevertheless, scientific studies demonstrating its anticonvulsant properties and the nature of the bioactive constituents are lacking. The aim of this study was to evaluate the anticonvulsant activities of the Moringa oleifera leaves in non-polar vs. polar extracts using behavioral and electroencephalographic (EEG) analyses in rodents. First, PTZ (80 mg/kg, i.p.)-induced tonic-clonic seizures were assayed via a dose-response (100, 200 and 300 mg/kg, i.p.) evaluation in mice. Then, a dosage of the extracts (100 or 300 mg/kg) and one metabolite (30 mg/kg, i.p.) was selected to evaluate its effect on PTZ (35 mg/kg, i.p.)-induced EEG paroxystic activities in rats compared to the effects of ethosuximide (reference anticonvulsant drug, 100 mg/kg, i.p.). Latent onset of the first paroxystic spike, first seizure and frequency as well as seizure severity, were determined using Racine's scale. Moringa oleifera ethanol and hexane extracts produced a delay in the seizure latency in mice and rats; this effect was improved in the presence of the hexane extract containing the active metabolite hexadecanoic acid. The anticonvulsant effects were corroborated in the spectral analysis by the potency of the EEG due to a reduction in the spike frequency and amplitude, as well as in the duration and severity of the seizures. The effects of the hexane extract resembled those observed in the reference antiepileptic drug ethosuximide. Moringa oleifera leaves possess anticonvulsant activities due to the complementary of the non-polar and polar constituents. However, the non-polar constituents appear to exert an important influence via the partial participation of fatty acids, providing evidence of the effects of this plant in epilepsy therapy. Copyright © 2017. Published by Elsevier GmbH.

  17. Secondary metabolites of cyanobacteria Nostoc sp.

    Science.gov (United States)

    Kobayashi, Akio; Kajiyama, Shin-Ichiro

    1998-03-01

    Cyanobacteria attracted much attention recently because of their secondary metabolites with potent biological activities and unusual structures. This paper reviews some recent studies on the isolation, structural, elucidation and biological activities of the bioactive compounds from cyanobacteria Nostoc species.

  18. A Procedure for the Rapid Determination of 226Ra and 228Ra in Drinking Water by Liquid Scintillation Counting

    International Nuclear Information System (INIS)

    2014-01-01

    Since 2004, the environment programme of the IAEA has included activities aimed at the development of a set of procedures for the determination of radionuclides in terrestrial environmental samples. Reliable, comparable and ‘fit for purpose’ results are essential requirements for any decision based on analytical measurements. For the analyst, tested and validated analytical procedures are extremely important tools for the production of such data. For maximum utility, such procedures should be comprehensive, clearly formulated and readily available to both the analyst and the customer. This publication describes a procedure for the rapid determination of 226 Ra and 228 Ra in drinking water. The determination of radium in drinking water is important for protecting human health, since the consumption of drinking water containing radium may lead to an accumulation in the body, contributing to the radiological dose. The method is based on the separation of 226 Ra and 228 Ra from interfering elements using PbSO 4 and Ba(Ra)SO 4 coprecipitation steps. The isotopes 226 Ra and 228 Ra are then determined by liquid scintillation counting. The procedure is expected to be of general use to a wide range of laboratories, including the laboratories of the Analytical Laboratories for the Measurement of Environmental Radioactivity (ALMERA) network, both in emergency situations and for routine environmental monitoring purposes. The method was established after an extensive review of papers from the scientific literature, and was tested and validated in terms of repeatability and trueness (relative bias) in accordance with International Organization for Standardization guidelines. Reproducibility tests were performed at expert laboratories. The calculation of massic activities, uncertainty budget, decision threshold and detection limit are also described

  19. High-Speed RaPToRS

    Science.gov (United States)

    Henchen, Robert; Esham, Benjamin; Becker, William; Pogozelski, Edward; Padalino, Stephen; Sangster, Thomas; Glebov, Vladimir

    2008-11-01

    The High-Speed Rapid Pneumatic Transport of Radioactive Samples (HS-RaPToRS) system, designed to quickly and safely move radioactive materials, was assembled and tested at the Mercury facility of the Naval Research Laboratory (NRL) in Washington D.C. A sample, which is placed inside a four-inch-diameter carrier, is activated before being transported through a PVC tube via airflow. The carrier travels from the reaction chamber to the end station where it pneumatically brakes prior to the gate. A magnetic latch releases the gate when the carrier arrives and comes to rest. The airflow, optical carrier-monitoring devices, and end gate are controlled manually or automatically with LabView software. The installation and testing of the RaPToRS system at NRL was successfully completed with transport times of less than 3 seconds. The speed of the carrier averaged 16 m/s. Prospective facilities for similar systems include the Laboratory for Laser Energetics and the National Ignition Facility.

  20. Roles of different forms of cytochrome P450 in the activation of the promutagen 6-aminochrysene to genotoxic metabolites in human liver microsomes.

    Science.gov (United States)

    Yamazaki, H; Mimura, M; Oda, Y; Inui, Y; Shiraga, T; Iwasaki, K; Guengerich, F P; Shimada, T

    1993-07-01

    We reported previously that the potent mutagen 6-aminochrysene is catalyzed principally by rat liver microsomal P4501A and P4502B enzymes to reactive metabolites that induce umu gene expression in O-acetyltransferase-over-expressing strain Salmonella typhimurium NM2009; the proposal was made that there are different mechanisms in the formation of reactive N-hydroxylated and diolepoxide metabolites by P450 enzymes (Yamazaki, H. and Shimada, T., Biochem. Pharmacol., 44, 913-920, 1992). Here we further examined the roles of human liver P450 enzymes and the mechanism of activation of 6-aminochrysene by rat and human P450 enzymes in the Salmonella tester strains. Liver microsomes from 18 different human samples catalyzed activation of 6-aminochrysene more efficiently in S. typhimurium NM2009 than in the original strain of S. typhimurium TA1535/pSK1002. The rates of 6-aminochrysene activation in 18 human liver samples showed good correlation to the contents of P4502B6 as well as contents of P4503A4 and the respective mono-oxygenase activities catalyzed by P4503A4. Among purified P450 enzymes examined, P4501A2 as well as P4503A4 were highly active in transforming 6-amino-chrysene to reactive metabolites, suggesting the involvement of different human P450 enzymes in the reaction. Four human samples that contained relatively high levels of particular P450 enzymes in their microsomes were selected and used for further characterization. Liver microsomes from human samples HL-13 and HL-4 that contained the highest levels of P4502B6 and P4503A4 respectively, were sensitive to the respective antibodies raised against monkey P4502B and human P4503A4; the activity in sample HL-16 having the highest level of P4501A2 was inhibited by anti-P4501A2 IgG. alpha-Naphthoflavone enhanced the activation of 6-aminochrysene very significantly in human liver microsomes enriched in P4503A4 and P4502B6 enzymes. Pentachlorophenol, an inhibitor of acetyltransferase activity, suppressed the

  1. Determination of Ra-223 in human excretion samples by means of α-spectrometry; Bestimmung von {sup 223}Ra in Ausscheidungsproben mittels α-Spektrometrie

    Energy Technology Data Exchange (ETDEWEB)

    Zoriy, M.V.; Froning, M.; Hill, P. [Forschungszentrum Juelich GmbH (Germany). Geschaeftsbereich Strahlenschutz und Sicherheit

    2015-07-01

    To ensure the safety of occupationally exposed person for possible incorporation of {sup 223}Ra during the handling with Alpharadin / Xofigo {sup registered}, the determination of {sup 223}Ra activity in its excretion sample (e.g, in a stool sample) might be of great importance. To assess the {sup 223}Ra activity in human faeces samples a new analytical method was developed in our laboratory. The determination is performed by means of grid-ionization a-spectrometry. After a relatively simple sample preparation procedure (usually within max. 6 hours) and the addition of an internal standard, a direct determination of {sup 223}Ra with the grid ionization chamber (GIK) is possible. The method was optimized and successfully tested. The procedure-related LOD for {sup 223}Ra in a 24-hour faeces sample was 0.1 Bq/Probe.

  2. 226Ra measurement by thermal ionisation mass spectrometry: Use of 226Ra and 14C for groundwater dating

    International Nuclear Information System (INIS)

    Dever, L.

    1997-01-01

    Recent developments in thermal ionisation mass spectrometry (TIMS) and in chemical separation Ra and Ba allow to analyse 226 Ra on smaller water samples ( 3 litres). The sampling has been realised on the Chalk aquifer of the Paris basin. The water samples have been collected in the unsaturated zone using in situ filtering devices and in the unconfined and confined parts of the aquifer in the boreholes used for public water supply. 226 Ra contents vary from 0.064±0.02 dpm/kg (n=6) in the unsaturated zone to 0.119±0.069 dpm/kg (n=7) in the unconfined aquifer and 0.319±0.057 dpm/kg (n=9) in the confined aquifer. For all the samples the 226 Ra/ 238 U activity ratios are much lower than the secular equilibrium. This points out that the two isotopes have different input function in the water during the mineralisation of the solution. The good correlation (r 2 =0.9) between the 226 Ra and Sr indicates that dissolution of Chalk is the dominant mechanism of mineralisation in 226 Ra of the solution. In the Chalk the mineralisation of the water occurs in the first metres of the unsaturated zone, during the water percolation the water rock interaction takes place through dissolution and precipitation of calcite in a non steady state. According to his distribution coefficient Sr is then a better tracer of dissolution/precipitation process than Ba. Using a geochemical model based on 226 Ra/Sr and Sr/Ca ratios an 'age' of the water could be determined. With 226 Ra half life of 1620 years we obtain 'ages' varying from 150 years to 1950 years in the unconfined aquifer. For the confined part of the aquifer where the redox condition is different it is necessary to use a geochemical model based on the U concentration in the water, the 226 Ra gives in such case ages varying from 1.8ka to 12.8ka. The radiocarbon ages obtained through usual chemical and/or isotopic models are quite similar and an isochrome between 226 Ra and 14 C ages can be calculated between 0 and 8ka

  3. 226Ra and 228Ra tracer study on nutrient transport in east coastal waters of Hainan Island, China

    Directory of Open Access Journals (Sweden)

    Ni Su

    2011-06-01

    Full Text Available Material fluxes (e.g., nutrients from coastal waters to offshore areas play an important role in controlling the water quality of the adjacent sea areas not only by increasing nutrient concentration but also by changing nutrient structures. In this study, naturally occurring isotopes, 226Ra and 228Ra, were measured with the alpha spectrometry in the Wenjiao-Wenchang and Wanquan estuaries and adjacent sea areas along the east coast of Hainan Island. The excess 226Ra and 228Ra activities were observed by comparison with the values derived from the conservative mixing of freshwater and seawater end-members in both estuaries. Using a one-dimensional diffusion model, the horizontal eddy diffusion coefficient of 3.16 x 105 cm2/s, for nutrients diffusing from their sources, was derived from 228Ra activities. Consequently, the corresponding nutrient fluxes flowing into the coastal waters were assessed. The results can provide useful information for the study of the mixing and exchange processes of coastal waters as well as dissoluble pollutant transport in this sea area.

  4. A ginseng saponin metabolite-induced apoptosis in HepG2 cells involves a mitochondria-mediated pathway and its downstream caspase-8 activation and Bid cleavage

    International Nuclear Information System (INIS)

    Oh, Seon-Hee; Lee, Byung-Hoon

    2004-01-01

    20-O-(β-D-Glucopyranosyl)-20(S)-protopanaxadiol (IH901), an intestinal bacterial metabolite of ginseng saponin formed from ginsenosides Rb1, Rb2, and Rc, is suggested to be a potential chemopreventive agent. Here, we show that IH901 induces apoptosis in human hepatoblastoma HepG2 cells. IH901 led to an early activation of procaspase-3 (12 h posttreatment), and the activation of caspase-8 became evident only later (18 h posttreatment). Caspase activation was a necessary requirement for apoptosis because caspase inhibitors significantly inhibited cell death by IH901. Treatment of HepG2 cells with IH901 also induced the cleavage of cytosolic factors such as Bid and Bax and translocation of truncated Bid (tBid) to mitochondria. A time-dependent release of cytochrome c from mitochondria was observed, which was accompanied by activation of caspase-9. A broad-spectrum caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD-fmk), and a specific inhibitor for caspase-8, N-benzyloxycarbonyl-Ile-Glu-Thr-Asp-fluoromethylketone (zIETD-fmk), abrogated Bid processing and translocation, and caspase-3 activation. Cytochrome c release was inhibited by zVAD-fmk, however, the inhibition by zIETD-fmk was not complete. The activation of caspase-8 was inhibited not only by zIETD-fmk but also by zVAD-fmk. The results, together with the kinetic change of caspase activation, indicate that activation of caspase-8 occurred downstream of caspase-3 and -9. Our data suggest that the activation of caspase-8 after early caspase-3 activation might act as an amplification loop necessary for successful apoptosis. Primary hepatocytes isolated from normal Sprague-Dawley rats were not affected by IH901 (0-60 μM). The very low toxicity in normal hepatocytes and high activity in hepatoblastoma HepG2 cells suggest that IH901 is a promising experimental cancer chemopreventive agent

  5. A new and fast DLLME-CE method for the enantioselective analysis of zopiclone and its active metabolite after fungal biotransformation.

    Science.gov (United States)

    de Albuquerque, Nayara Cristina Perez; de Gaitani, Cristiane Masetto; de Oliveira, Anderson Rodrigo Moraes

    2015-05-10

    Zopiclone (ZO) is a chiral drug that undergoes extensive metabolism to N-desmethylzopiclone (N-Des-ZO) and zopiclone-N-oxide (N-Ox-ZO). Pharmacological studies have shown (S)-N-Des-ZO metabolite presents anxiolytic activity and a patent for this metabolite was requested for anxiety treatment and related disorders. In this context, biotransformation employing fungi may be a promising strategy to obtain N-Des-ZO. To perform the biotransformation study in this work, an enantioselective method based on capillary electrophoresis (CE) and dispersive liquid-liquid microextraction (DLLME) was developed. CE analyses were carried out in sodium phosphate buffer (pH 2.5; 50mmolL(-1)) containing 0.5% (w/v) carboxymethyl-β-CD, at a constant voltage of +25kV. DLLME was conducted using 2mL of liquid culture medium pH 9.5. Chloroform (100μL) and methanol (300μL) were employed as extraction and disperser solvent, respectively. After CE and DLLME optimization, the analytical method was fully validated. The method was linear over a concentration range of 90-6000ngmL(-1) for each ZO enantiomer (r>0.999) and 50-1000ngmL(-1) for each N-Des-ZO enantiomer (r>0.998). Absolute recovery of 51 and 82% was achieved for N-Des-ZO and ZO, respectively. The accuracy and precision results agreed with the EMA (European Medicines Agency) guideline, and so did the stability study. Application of the developed method in a biotransformation study was conducted in order to investigate the ability of fungi, belonging to the genus Cunninghamella, in metabolizing ZO chiral drug. Fungi Cunninghamella elegans ATCC 10028B and Cunninghamella echinulata var elegans ATCC 8688A demonstrated to be able to enantioselectively biotransform ZO to its active metabolite, N-Des-ZO. Therefore, the proposed goals of this work, i.e. a fast DLLME-CE method and an outstanding strategy to obtain N-Des-ZO, were successfully attained. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Biodistribution and metabolism of the anti-influenza drug [{sup 11}C]oseltamivir and its active metabolite [{sup 11}C]Ro 64-0802 in mice

    Energy Technology Data Exchange (ETDEWEB)

    Hatori, Akiko; Arai, Takuya; Yanamoto, Kazuhiko; Yamasaki, Tomoteru; Kawamura, Kazunori; Yui, Joji; Konno, Fujiko; Nakao, Ryuji; Suzuki, Kazutoshi [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences (NIRS), Inage-ku, Chiba 263-8555 (Japan); Zhang Mingrong [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences (NIRS), Inage-ku, Chiba 263-8555 (Japan)], E-mail: zhang@nirs.go.jp

    2009-01-15

    Introduction: Oseltamivir phosphate (Tamiflu) is an orally active anti-influenza drug, which is hydrolyzed by esterase to its carboxylate metabolite Ro 64-0802 with potent activity to inhibit the influenza virus. The abnormal behavior and death associated with the use of oseltamivir have developed into a major problem in Japan where Tamiflu is often prescribed for seasonal influenza. It is critical to determine the amount of oseltamivir and Ro 64-0802 in the human brain and to elucidate the relationship between their amounts and neuropsychiatric side effects. The aim of this study was to evaluate [{sup 11}C]oseltamivir and [{sup 11}C]Ro 64-0802 in mice as promising positron emission tomography (PET) ligands for measuring their amounts in living brains. Methods: Whole-body biodistribution of [{sup 11}C]oseltamivir and [{sup 11}C]Ro 64-0802 was determined in mice using the dissection method and micro-PET. In vitro and in vivo metabolite assay was performed in the plasma and brain of mice. Results: Between 1 and 60 min after injection of [{sup 11}C]oseltamivir and [{sup 11}C]Ro 64-0802, 0.20-0.06% and 0.39-0.03% ID/g were detected in the mouse brains, respectively (dissection method). Radioactivity concentrations in the living brains between 0 and 90 min after injection were measured at standardized uptake values of 0.25-0.05 for [{sup 11}C]oseltamivir and 0.38-0.02 for [{sup 11}C]Ro 64-0802 (micro-PET). In vivo metabolite assay demonstrated the presence of [{sup 11}C]oseltamivir and [{sup 11}C]Ro 64-0802 in the brains after [{sup 11}C]oseltamivir injection. Conclusion: This study determined the distribution and metabolism of [{sup 11}C]oseltamivir and [{sup 11}C]Ro 64-0802 in mice. PET could be used to measure their amounts in the living brain and to elucidate the relationship between the amounts in the brain and the side effects of Tamiflu in the central nervous system.

  7. Recommendations for simulations to predict environmental concentrations of active substances of plant protection products and their metabolites in groundwater (PECgw) in the national assessment for authorisation in Germany

    Energy Technology Data Exchange (ETDEWEB)

    Holdt, Gabriele; Gallien, Peter; Nehls, Angelika [Umweltbundesamt Dessau (DE)] (and others)

    2011-09-15

    In the national assessment for authorisation in Germany the leaching behaviour of a plant protection product is determined in a stepwise procedure in accordance with FOCUS groundwater report (2009). The recommendations given in this paper here are related to tier 1 and tier 2, only. A further publication is planned for the tier 3 and tier 4 assessments in accordance with the principles provided by FOCUS. The tier 1 leaching assessment in the EU evaluation process is based on the nine FOCUS (2009) standard groundwater scenarios. In the member state evaluation for Germany, a sub-set of the standard scenarios with climatic and soil conditions found to be relevant for Ger-many are taken into account (Hamburg and Kremsmuenster). The soils of the two scenarios cover the pH-range of agricultural soils and allow the pH-dependent behaviour of compounds to be addressed. For the parameterisation of the degradation behaviour of an active substance and its metabolites in soil the recommendations of FOCUS should be followed. Normalised degradation rates may be taken from either laboratory or from field dissipation studies. For the parameterisation of the sorption behaviour of an active substance and its metabolites in soil the recommendations of FOCUS should be considered. With respect to the correlation of degradation and/or sorption behaviour to soil properties (pH, OC) further detailed recommendations are provided to facilitate the selection of conservative sorption parameters for leaching assessment. Proposals and detailed schemes for the handling of the DT50 and Kfoc values (including their variability) are given. Further recommendations are given in this paper on how to use other modelling parameters e.g. crop rotation, plant uptake factor, formation of metabolites, correlations / multi-correlations of substance parameters to soil properties, and application of statistical methods. Tier 2 of the leaching assessment consists of more refined modelling approaches. This

  8. Simultaneous Determination of Antipsychotic Drugs and Their Active Metabolites by LC-MS-MS and its Application to Therapeutic Drug Monitoring.

    Science.gov (United States)

    Miroshnichenko, Igor I; Baymeeva, Natalia V

    2018-04-07

    A quantitative method was developed to support therapeutic drug monitoring of eight antipsychotic drugs: chlorpromazine, haloperidol, zuclopenthixol, clozapine, risperidone, quetiapine, aripiprazole or olanzapine and some active metabolites (dehydroaripiprazole, N-desmethylclozapine and 9-hydroxyrisperidone) in human serum. Separation of the compounds was achieved using a Zorbax SB-C18 (150 mm × 4.6 mm, 5 μm) column and mass-spectrometric detection in multiple reaction monitoring mode. Human blood samples were collected in vacutainer tubes and the analytes were extracted with methyl-tert-butyl ether. The lower limits of quantitation were equal 0.5-1 ng/mL for all analytes. The method was applied with success to serum samples from schizophrenic patients undergoing polypharmacy with two or more different antipsychotic drugs. Precision data, accuracy results were satisfactory, and no interference from other psychotropic drugs was found. Hence, the method is suitable for the TDM of the analytes in psychotic patients' serum.

  9. The pharmacokinetics of oxcarbazepine and its active metabolite 10-hydroxy-carbazepine in healthy subjects and in epileptic patients treated with phenobarbitone or valproic acid.

    Science.gov (United States)

    Tartara, A; Galimberti, C A; Manni, R; Morini, R; Limido, G; Gatti, G; Bartoli, A; Strada, G; Perucca, E

    1993-01-01

    The kinetics of oxcarbazepine (OXC) and its active metabolite 10-hydroxy-carbazepine (10-OH-CZ) after a single oral OXC dose (600 mg) were compared in healthy control subjects and in epileptic patients treated with phenobarbitone or sodium valproate (n = 8 in each group). In all groups, serum 10-OH-CZ concentrations were much higher than those of the parent drug. In patients on valproate, the kinetics of OXC and 10-OH-CZ did not differ significantly from those observed in controls. In patients on phenobarbitone, AUC values of both OXC and 10-OH-CZ were lower than in controls (2.9 +/- 0.4 vs 5.1 +/- 0.7 microg ml(-1) h and 89 +/- 7 vs 119 +/- 10 microg ml(-1) h respectively, means +/- s.e. mean, P effect is unlikely to be of great clinical significance. PMID:12959317

  10. Phytotoxic activity against Bromus tectorum for secondary metabolites of a seed-pathogenic Fusarium strain belonging to the F. tricinctum species complex.

    Science.gov (United States)

    Masi, Marco; Meyer, Susan; Pescitelli, Gennaro; Cimmino, Alessio; Clement, Suzette; Peacock, Beth; Evidente, Antonio

    2017-12-01

    The winter annual grass Bromus tectorum (cheatgrass) has become highly invasive in semiarid ecosystems of western North America. In these areas, a natural phenomenon, complete cheatgrass stand failure ('die-off'), is apparently caused by a complex interaction among soilborne fungal pathogens. Several Fusarium strains belonging to the Fusarium tricinctum species complex were isolated from these soils and found to be pathogenic on B. tectorum seeds. One of these strains was produced in cheatgrass seed culture to evaluate its ability to produce phytotoxins. Six metabolites were isolated and identified by spectroscopic methods (essentially 1D and 2D NMR and ESIMS) as acuminatopyrone (1), blumenol A (2), chlamydosporol (3), isochlamydosporol (4), ergosterol (5) and 4-hydroxybenzaldehyde (6). Upon testing against B. tectorum in a seedling bioassay, (6) the coleoptile and radicle length of cheatgrass seedlings were significantly reduced. Compounds 1 and 2 showed moderate activity, while 3-5 were not significantly different from the control.

  11. Inventory of 226Ra, 228Ra and 210Pb in marine sediments cores of Southwest Atlantic Ocean

    International Nuclear Information System (INIS)

    Costa, Alice M.R.; Oliveira, Joselene de; Figueira, Rubens C.L.; Mahiques, Michel M.; Sousa, Silvia H.M.

    2015-01-01

    210 Pb (22.3 y) is a radioactive isotope successfully applied as tracer of sediment dating of the last 100-150 years. The application of 226 Ra and 228 Ra as paleoceanographic tracers (half-lives of 1,600 y and 5.7 y, respectively) also gives some information of ocean's role in past climate change. In this work, it was analyzed 2 sediment cores collect at Southwest Atlantic Ocean. The sediments samples were freeze-dried and acid digested in microwave. It was carried out a radiochemical separation of 226 Ra, 228 Ra and 210 Pb and performed a gross alpha and gross beta measurement of both precipitates Ba(Ra)SO 4 and PbCrO 4 in a low background gas-flow proportional counter. Activity concentrations of 226 Ra ranged from 45 Bq kg -1 to 70 Bq kg -1 in NAP-62 and from 57 Bq kg -1 to 82 Bq kg -1 in NAP-63 samples. The concentration of 228 Ra varied between 37 Bq kg -1 and 150 Bq kg -1 in NAP-62 and between 23 Bq kg -1 and 111 Bq kg -1 in NAP-63 samples. The concentration of total 210 Pb ranged from 126 Bq kg -1 to 256 Bq kg -1 in NAP-62 and from 63 Bq kg -1 to 945 Bq kg -1 in NAP-63 samples. Results of 210 Pb uns varied from 68 Bq kg -1 to 192 Bq kg -1 for NAP-62, while varied from <4.9 Bq kg -1 to 870 Bq kg -1 in NAP-63 profile. Increased values of 210 Pb uns were found on the top of both NAP-62 and NAP- 63 sediment profile. (author)

  12. Leaching of RA-226 contaminated gravel using different aqueous treatments

    Energy Technology Data Exchange (ETDEWEB)

    Mamoon, A; Abulfaraj, W H; Sohsah, M A [King Abdulaziz University, Jeddah, Saudi Arbabia (Saudi Arabia)

    1997-12-31

    Investigation of the efficiencies of different aqueous leaching treatments was carried out on gravel artificially contaminated with Ra-226. The extent of leaching efficiency was determined in terms of Ra-226 and its daughter Rn-222. Liquid scintillation counting using high efficiency mineral oil based liquid scintillator was the technique adopted for measuring Ra-226 and Rn-222 leached off the contaminated gravel. Water, dilute solutions of barium chloride and HCl were used as leachants. Different masses of gravel were leached with 200 mL of leachant for various contact time periods. The leached Rn-222 activity measured was plotted vs the decay factor e; from which Rn-222 and Ra-226 originally present in the sample were determined. Several leaching parameters were tested; namely type of leachant, leachant volume/gravel mass ratio, leachant contact time, effect of varying Ba Cl{sub 2} concentration, and successive leaching. Optimization of the leaching parameters for desorption of Ra-226 off the contaminated gravel under laboratory conditions may help determine the ideal conditions for remediating soil contaminated with radium or chemically similar radionuclides. 7 figs.

  13. Simultaneous quantification of lenalidomide, ibrutinib and its active metabolite PCI-45227 in rat plasma by LC-MS/MS: application to a pharmacokinetic study.

    Science.gov (United States)

    Veeraraghavan, Sridhar; Viswanadha, Srikant; Thappali, Satheeshmanikandan; Govindarajulu, Babu; Vakkalanka, Swaroopkumar; Rangasamy, Manivannan

    2015-03-25

    Efficacy assessments using a combination of ibrutinib and lenalidomide necessitate the development of an analytical method for determination of both drugs in plasma with precision. A high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of lenalidomide, ibrutinib, and its active metabolite PCI45227 in rat plasma. Extraction of lenalidomide, ibrutinib, PCI45227 and tolbutamide (internal standard; IS) from 50 μl rat plasma was carried out by liquid-liquid extraction with ethyl acetate:dichloromethane (90:10) ratio. Chromatographic separation of analytes was performed on YMC pack ODS AM (150 mm × 4.6 mm, 5 μm) column under gradient conditions with acetonitrile:0.1% formic acid buffer as the mobile phases at a flow rate of 1 ml/min. Precursor ion and product ion transition for analytes and IS were monitored on a triple quadrupole mass spectrometer, operated in the selective reaction monitoring with positive ionization mode. Method was validated over a concentration range of 0.72-183.20 ng/ml for ibrutinib, 0.76-194.33 ng/ml for PCI-45227 and 1.87-479.16 ng/ml for lenalidomide. Mean extraction recovery for ibrutinib, PCI-45227, lenalidomide and IS of 75.2%, 84.5%, 97.3% and 92.3% were consistent across low, medium, and high QC levels. Precision and accuracy at low, medium and high quality control levels were less than 15% across analytes. Bench top, wet, freeze-thaw and long term stability was evaluated for all the analytes. The analytical method was applied to support a pharmacokinetic study of simultaneous estimation of lenalidomide, ibrutinib, and its active metabolite PCI-45227 in Wistar rat. Assay reproducibility was demonstrated by re-analysis of 18 incurred samples. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. The inotropic effect of the active metabolite of levosimendan, OR-1896, is mediated through inhibition of PDE3 in rat ventricular myocardium.

    Directory of Open Access Journals (Sweden)

    Øivind Ørstavik

    Full Text Available We recently published that the positive inotropic response (PIR to levosimendan can be fully accounted for by phosphodiesterase (PDE inhibition in both failing human heart and normal rat heart. To determine if the PIR of the active metabolite OR-1896, an important mediator of the long-term clinical effects of levosimendan, also results from PDE3 inhibition, we compared the effects of OR-1896, a representative Ca2+ sensitizer EMD57033 (EMD, levosimendan and other PDE inhibitors.Contractile force was measured in rat ventricular strips. PDE assay was conducted on rat ventricular homogenate. cAMP was measured using RII_epac FRET-based sensors.OR-1896 evoked a maximum PIR of 33 ± 10% above basal at 1 μM. This response was amplified in the presence of the PDE4 inhibitor rolipram (89 ± 14% and absent in the presence of the PDE3 inhibitors cilostamide (0.5 ± 5.3% or milrinone (3.2 ± 4.4%. The PIR was accompanied by a lusitropic response, and both were reversed by muscarinic receptor stimulation with carbachol and absent in the presence of β-AR blockade with timolol. OR-1896 inhibited PDE activity and increased cAMP levels at concentrations giving PIRs. OR-1896 did not sensitize the concentration-response relationship to extracellular Ca2+. Levosimendan, OR-1896 and EMD all increased the sensitivity to β-AR stimulation. The combination of either EMD and levosimendan or EMD and OR-1896 further sensitized the response, indicating at least two different mechanisms responsible for the sensitization. Only EMD sensitized the α1-AR response.The observed PIR to OR-1896 in rat ventricular strips is mediated through PDE3 inhibition, enhancing cAMP-mediated effects. These results further reinforce our previous finding that Ca2+ sensitization does not play a significant role in the inotropic (and lusitropic effect of levosimendan, nor of its main metabolite OR-1896.

  15. Enhancement of anti-inflammatory activity of Aloe vera adventitious root extracts through the alteration of primary and secondary metabolites via salicylic acid elicitation.

    Directory of Open Access Journals (Sweden)

    Yun Sun Lee

    Full Text Available Aloe vera (Asphodeloideae is a medicinal plant in which useful secondary metabolites are plentiful. Among the representative secondary metabolites of Aloe vera are the anthraquinones including aloe emodin and chrysophanol, which are tricyclic aromatic quinones synthesized via a plant-specific type III polyketide biosynthesis pathway. However, it is not yet clear which cellular responses can induce the pathway, leading to production of tricyclic aromatic quinones. In this study, we examined the effect of endogenous elicitors on the type III polyketide biosynthesis pathway and identified the metabolic changes induced in elicitor-treated Aloe vera adventitious roots. Salicylic acid, methyl jasmonate, and ethephon were used to treat Aloe vera adventitious roots cultured on MS liquid media with 0.3 mg/L IBA for 35 days. Aloe emodin and chrysophanol were remarkably increased by the SA treatment, more than 10-11 and 5-13 fold as compared with untreated control, respectively. Ultra-performance liquid chromatography-electrospray ionization mass spectrometry analysis identified a total of 37 SA-induced compounds, including aloe emodin and chrysophanol, and 3 of the compounds were tentatively identified as tricyclic aromatic quinones. Transcript accumulation analysis of polyketide synthase genes and gas chromatography mass spectrometry showed that these secondary metabolic changes resulted from increased expression of octaketide synthase genes and decreases in malonyl-CoA, which is the precursor for the tricyclic aromatic quinone biosynthesis pathway. In addition, anti-inflammatory activity was enhanced in extracts of SA-treated adventitious roots. Our results suggest that SA has an important role in activation of the plant specific-type III polyketide biosynthetic pathway, and therefore that the efficacy of Aloe vera as medicinal agent can be improved through SA treatment.

  16. Enhancement of anti-inflammatory activity of Aloe vera adventitious root extracts through the alteration of primary and secondary metabolites via salicylic acid elicitation.

    Science.gov (United States)

    Lee, Yun Sun; Ju, Hyun Kyoung; Kim, Yeon Jeong; Lim, Tae-Gyu; Uddin, Md Romij; Kim, Yeon Bok; Baek, Jin Hong; Kwon, Sung Won; Lee, Ki Won; Seo, Hak Soo; Park, Sang Un; Yang, Tae-Jin

    2013-01-01

    Aloe vera (Asphodeloideae) is a medicinal plant in which useful secondary metabolites are plentiful. Among the representative secondary metabolites of Aloe vera are the anthraquinones including aloe emodin and chrysophanol, which are tricyclic aromatic quinones synthesized via a plant-specific type III polyketide biosynthesis pathway. However, it is not yet clear which cellular responses can induce the pathway, leading to production of tricyclic aromatic quinones. In this study, we examined the effect of endogenous elicitors on the type III polyketide biosynthesis pathway and identified the metabolic changes induced in elicitor-treated Aloe vera adventitious roots. Salicylic acid, methyl jasmonate, and ethephon were used to treat Aloe vera adventitious roots cultured on MS liquid media with 0.3 mg/L IBA for 35 days. Aloe emodin and chrysophanol were remarkably increased by the SA treatment, more than 10-11 and 5-13 fold as compared with untreated control, respectively. Ultra-performance liquid chromatography-electrospray ionization mass spectrometry analysis identified a total of 37 SA-induced compounds, including aloe emodin and chrysophanol, and 3 of the compounds were tentatively identified as tricyclic aromatic quinones. Transcript accumulation analysis of polyketide synthase genes and gas chromatography mass spectrometry showed that these secondary metabolic changes resulted from increased expression of octaketide synthase genes and decreases in malonyl-CoA, which is the precursor for the tricyclic aromatic quinone biosynthesis pathway. In addition, anti-inflammatory activity was enhanced in extracts of SA-treated adventitious roots. Our results suggest that SA has an important role in activation of the plant specific-type III polyketide biosynthetic pathway, and therefore that the efficacy of Aloe vera as medicinal agent can be improved through SA treatment.

  17. Determination of Ra-226 by gamma-ray spectrometry

    International Nuclear Information System (INIS)

    Martinez Lobo, A.

    1988-01-01

    This work deals with the method of determination of 226 Ra by low energy photon spectrometry. For this purpose, the interference due to 235 U, that emits a photon with a close energy, has to be considered. The contribution of 235 U to the 186 KeV photopeak is studied through the 63 KeV 234 Th and the 144 KeV 235 U emissions. From the minimum detectable activity of 226 Ra it is discussed the applicability of this method to several kind of samples. (Author)

  18. LCA versus RA - an introduction

    DEFF Research Database (Denmark)

    Olsen, Stig Irving

    2000-01-01

    Risk Assessment (RA) of chemicals is an environmental management tool used to assess the risk of specific chemicals, which are harmful to man or the environment under certain circumstances of use or in certain environmental recipients. Life Cycle Assessment (LCA) or environmental assessment...... of Industrial Products) developed in Denmark (Wenzel et al., 1997), respectively. The interactions between the two tools can be viewed from two different angles: 1. As a general reflection of how the tools supplement each other in the total environmental effort. 2. As an assessment of coincidences...... on Principles and Methods for Hazard and Risk Assessment)focuses on an assessment of the toxicological and ecotoxicological risks, the focus of this article's comparison of assessment principles, data requirements etc. will be on the assessment of toxicity and ecotoxicity in EDIP's impact assessment methodology...

  19. Optimum RA reactor fuelling scheme

    International Nuclear Information System (INIS)

    Strugar, P.; Nikolic, V.

    1965-10-01

    Ideal reactor refueling scheme can be achieved only by continuous fuel elements movement in the core, which is not possible, and thus approximations are applied. One of the possible approximations is discontinuous movement of fuel elements groups in radial direction. This enables higher burnup especially if axial exchange is possible. Analysis of refueling schemes in the RA reactor core and schemes with mixing the fresh and used fuel elements show that 30% higher burnup can be achieved by applying mixing, and even 40% if reactivity due to decrease in experimental space is taken into account. Up to now, mean burnup of 4400 MWd/t has been achieved, and the proposed fueling scheme with reduction of experimental space could achieve mean burnup of 6300 MWd/t which means about 25 Mwd/t per fuel channel [sr

  20. RA Reactor applications, Annex A

    International Nuclear Information System (INIS)

    Martinc, R.; Cupac, S.; Stanic, A.

    1990-01-01

    RA reactor was not operated during the past five years due to the renewal and reconstruction of the reactor systems, which in underway. In the period from 1986-1990, reactor was operated only 144 MWh in 1986, for the need of testing the reactor systems and possibility of irradiating 125 I. Reactor will not be operated in 1991 because of the exchange of complete instrumentation which is planned to be finished by the end of 1991. It is expected to start operation in May 1992. That is why this annex includes the plan of reactor operation for period of nine months starting from from the moment of start-up. It is planned to operate the reactor at 0.02 MW power first three months, to increase the power gradually and reach 3.5 MW after 8 months of operation. It is foreseen to operate the reactor at 4.7 MW from the tenth month on [sr

  1. RaPToRS Sample Delivery System

    Science.gov (United States)

    Henchen, Robert; Shibata, Kye; Krieger, Michael; Pogozelski, Edward; Padalino, Stephen; Glebov, Vladimir; Sangster, Craig

    2010-11-01

    At various labs (NIF, LLE, NRL), activated material samples are used to measure reaction properties. The Rapid Pneumatic Transport of Radioactive Samples (RaPToRS) system quickly and safely moves these radioactive samples through a closed PVC tube via airflow. The carrier travels from the reaction chamber to the control and analysis station, pneumatically braking at the outlet. A reversible multiplexer routes samples from various locations near the shot chamber to the analysis station. Also, the multiplexer allows users to remotely load unactivated samples without manually approaching the reaction chamber. All elements of the system (pneumatic drivers, flow control valves, optical position sensors, multiplexers, Geiger counters, and release gates at the analysis station) can be controlled manually or automatically using a custom LabVIEW interface. A prototype is currently operating at NRL in Washington DC. Prospective facilities for Raptors systems include LLE and NIF.

  2. Fluoxetine and its active metabolite norfluoxetine disrupt estrogen synthesis in a co-culture model of the feto-placental unit.

    Science.gov (United States)

    Hudon Thibeault, Andrée-Anne; Laurent, Laetitia; Vo Duy, Sung; Sauvé, Sébastien; Caron, Patrick; Guillemette, Chantal; Sanderson, J Thomas; Vaillancourt, Cathy

    2017-02-15

    The effects of fluoxetine, one of the most prescribed selective serotonin-reuptake inhibitors (SSRIs) during pregnancy, and its active metabolite norfluoxetine were studied on placental aromatase (CYP19) and feto-placental steroidogenesis. Fluoxetine did not alter estrogen secretion in co-culture of fetal-like adrenocortical (H295R) and trophoblast-like (BeWo) cells used as a model of the feto-placental unit, although it induced CYP19 activity, apparently mediated by the serotonin (5-HT) 2A receptor/PKC signaling pathway. Norfluoxetine decreased estrogen secretion in the feto-placental co-culture and competitively inhibited catalytic CYP19 activity in BeWo cells. Decreased serotonin transporter (SERT) activity in the co-culture was comparable to 17β-estradiol treatment of BeWo cells. This work shows that the complex interaction of fluoxetine and norfluoxetine with placental estrogen production, involves 5-HT-dependent and -independent mechanisms. Considering the crucial role of estrogens during pregnancy, our results raise concern about the impact of SSRI treatment on placental function and fetal health. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Toxicity of bifenazate and its principal active metabolite, diazene, to Tetranychus urticae and Panonychus citri and their relative toxicity to the predaceous mites, Phytoseiulus persimilis and Neoseiulus californicus.

    Science.gov (United States)

    Ochiai, Noriaki; Mizuno, Masayuki; Mimori, Norihiko; Miyake, Toshihiko; Dekeyser, Mark; Canlas, Liza Jara; Takeda, Makio

    2007-01-01

    Bifenazate is a novel carbazate acaricide discovered by Uniroyal Chemical (now Chemtura Corporation) for the control of phytophagous mites infesting agricultural and ornamental crops. Its acaricidal activity and that of its principal active metabolite, diazene, were characterized. Bifenazate and diazene had high toxicity and specificity both orally and topically to all life stages of Tetranychus urticae and Panonychus citri. Acute poisoning was observed with no temperature dependency. No cross-resistance was found to mites resistant to several other classes of acaricides, such as tebufenpyrad, etoxazole, fenbutatin oxide and dicofol. Bifenazate remained effective for a long time with only about a 10% loss of efficacy on T. urticae after 1 month of application in the field. All stages of development of the predatory mites, Phytoseiulus persimilis and Neoseiulus californicus, survived treatment by both bifenazate and diazene. When adult females of the two predatory mite species were treated with either bifenazate or diazene, they showed a normal level of fecundity and predatory activity in the laboratory, effectively suppressing spider mite population growth. Even when the predators were fed spider mite eggs that had been treated previously with bifenazate, they survived. These findings indicate that bifenazate is a very useful acaricide giving high efficacy, long-lasting activity and excellent selectivity for spider mites. It is, therefore, concluded that bifenazate is an ideal compound for controlling these pest mites.

  4. Circadian variation in metabolite and enzyme activities in the femoral and thoracic muscles of adult variegated grasshoppers, Zonocerus variegatus (Linnaeus, 1758 (Orthoptera: Pyrgomorphidae

    Directory of Open Access Journals (Sweden)

    Ademolu Kehinde Olutoyin

    2018-03-01

    Full Text Available The African variegated grasshopper, Zonocerus variegatus, exhibits daily variations in its feeding and destructive activities. A study to investigate circadian variation in metabolites (lipids, protein, glucose, K+, Ca2+, Mg2+, Cl− concentrations and enzymes (lipase, amylase, proteinase, α-glucosidase activities in the femoral and thoracic muscles of adult Z. variegatus was carried out by collecting samples at 06:00, 12:00, 18:00 and 24:00 hrs GMT. The four enzymes were present throughout the day in both thoracic and femoral muscles but at varying levels. Significantly (p<0.05 higher enzymes activities were measured during the day (between 06:00 and 18:00 hours GMT (except proteinase than at night (24:00 hrs. Organic substances in the two tissues were present in significantly higher concentrations during the day than at night. Similarly, significantly more inorganic substances were recorded in the afternoon (12:00-18:00 hrs than at night in both femoral and thoracic muscles. It can thus be concluded that locomotor activities in Z. variegatus reach a peak during the day.

  5. Operation and maintenance of the RA reactor, RA Research reactor. Annual report 1976; Pogon i odrzavanje reaktora RA, Izvestaj o radu u 1976. godini

    Energy Technology Data Exchange (ETDEWEB)

    Martinc, R [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

    1976-12-15

    During 1976 the Ra reactor was operating for about 30% shorter period than usual. The reason were extraordinary repair activities within regular and investment maintenance as well as repair of failures caused by neglected maintenance during previous 6 years. Delay was caused by unavailability of fuel (2% enriched fuel elements are spent) and the new 80% enriched fuel demanded experimental and theoretical analyses before being introduced into the core. Safety analyses concerned with using 80% enriched fuel both experimental and theoretical were successfully fulfilled. The December 1976 successful experimental campaign can be marked as end of the 17 years period of using 2% enriched fuel and start of the new period of using highly enriched fuel. This is significant not only for the reactor itself but for the users, because it would result in increase of neutron flux by 50% with the increase of costs by only 4%. Demand was submitted for obtaining the final license for transition operating regime with highly enriched fuel which would save at least 2 200 000 dinars. This will enable reactor operation in 1977 and later on, without interruption by 'critical' and other experiments related to new highly enriched fuel. A high number of repair and other urgent activities were fulfilled in order to enable safe operation. Some of these activities were done never before and some were neglected during past 6 years. The most important tasks were: purchase of Al tubes made of special alloy, fabrication and mounting of the fuel channel; overall investigation of reactor vessel leakage; repair of the heavy water pump; exchange of two vertical channels. basic equipment for construction of emergency cooling system was purchased. Hot cells are equipped for independent utilisation. [Serbo-Croat] Reaktor RA je u 1976. godini radio za oko 30% krace vreme od uobicajenog. Razlog su bill izuzetno veliki obim remontnih i drugih radova u okviru tekuceg i investicionog odrzavanja, kao i krupnih

  6. Measurement and Analysis of Specific Activities of 238U, 232Th,226Ra, 40K and 137Cs in Soil Samples from Phatthalung Province (Thailand) using Gamma Ray Spectrometry

    International Nuclear Information System (INIS)

    Daoh, Murnee; Kessaratikoon, Prasong; Udomsomporn, Suchin

    2011-06-01

    Full text: Specific activity of natural (238 U , 232 T h, 226 R a and 40 K ) and anthropogenic radionuclide (137 C s) in 109 soil samples collected from 11 districts in Phathalung province have been measured and analyzed. Experimental results were obtained by using a high purity germanium (HPGe) detector and gamma spectrometry analysis system at Nuclear and Material Physics laboratory in Department of Physics Faculty of Science Thaksin University Songkhla Campus. Gamma ray radioactive standard sources 60 C o, 137 C s and 133 B a were used to calibrate the measurement system. The KCl and two reference materials (RGU-1 and RGTh-1) obtained from the International Atomic Energy Agency were also used to analyze and compute the 40 K , 238 U (or 226 R a) and 232 T h specific activity in all soil samples. The IAEA/SL-2 was also used to evaluate the specific activity of 137 C s in all soil samples. The measuring time of each sample was 10,800 seconds. It was found that specific activity ranged from 148.17 to 11276.78 Bq/kg for 40 K , 58.29 to 518.45 Bq/kg for 226 R a, 8.40 to 236.19 Bq/kg for 232 T h and 0.00 tp 12.39 Bq/kg for 137 C s with mean values of 3573.35 ± 203.89 Bq/kg, 135.89 ± 6.71 Bq/kg, 76.34 ± 5.32 Bq/kg and 1.05 ± 0.70 Bq/kg respectively. Furthermore, absorbed dose rate in air (D), radium equivalent activity (Ra e q), external hazard index (H e x), and annual effective dose rate (AEDout) of this area were also evaluated by using the mean values of specific activities of the 40 K , 226 R a and 232 T h. Moreover, the experimental results were also compared with Office of Atoms for Peace (OAP) research data, Thailand and global radioactivity measurement and evaluations. The radioactive contour maps of specific activities of natural and anthropogenic radionuclides from this study were created by using the program ArcGis Version 9.2

  7. New Modified UPLC/Tandem Mass Spectrometry Method for Determination of Risperidone and Its Active Metabolite 9-Hydroxyrisperidone in Plasma: Application to Dose-Dependent Pharmacokinetic Study in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Essam Ezzeldin

    2017-01-01

    Full Text Available Sensitive and specific liquid-chromatography tandem mass spectrometry (UPLC-MS/MS assay has been developed and validated for simultaneous quantification of risperidone (RIS and its active metabolite 9-hydroxyrisperidone (9-OH-RIS in rat plasma using olanzapine (OLA as internal standard (IS. Pharmacokinetics of risperidone and its active metabolite 9-hydroxyrisperidone was compared across different doses (0.3, 1.0, and 6.0 mg/kg. Serial blood sample was collected over a time of 48 hours and analyzed for risperidone and its active metabolite 9-hydroxyrisperidone. The pharmacokinetics parameters including Cmax, tmax, and AUC were determined for risperidone and its active ingredient. The method was linear in the concentration range of 0.2–500 ng/mL for risperidone and 9-OH-risperidone, with coefficients of determination greater than 0.998 and lower limit of quantitation of 0.2 ng/mL. Blood levels of risperidone and its active metabolite were roughly dose-proportional. The method developed herein is simple and rapid and was successfully applied for dose-dependent pharmacokinetic study.

  8. Distribution of 226Ra and 228Ra in drinking water and dose assessment

    International Nuclear Information System (INIS)

    Ajay Kumar; Sugandhi, S.; Usha, N.; Rupali, K.; Gurg, R.P.

    2002-01-01

    The radioactivity concentrations of 226 Ra and 228 Ra have been analysed in 123 drinking water samples received from different regions of India. The maximum concentrations of 226 Ra and 228 Ra in drinking water are 8 mBq/l and 11.5 mBq/l respectively. The higher doses due to intake of 228 Ra through drinking water suggests that 228 Ra should also be measured in the assessment of ingestion dose to the population. The estimated committed effective doses range from 0.082 to 2.45 μSv/year and from 1.53 to 8.81 μSv/year for the ingestion of 226 Ra and 228 Ra respectively. (author)

  9. Status of the RA research reactor decommissioning project

    International Nuclear Information System (INIS)

    Ljubenov, V.; Nikolic, D.; Pesic, M.; Milosevic, M.; Kostic, Lj.; Steljic, M.; Sotic, O.; Antic, D. . E-mail address of corresponding author: vladan@vin.bg.ac.yu; Ljubenov, V.)

    2005-01-01

    The 6.5 MW heavy water RA research reactor at the VINCA Institute of Nuclear Sciences operated from 1959 to 1984. After 18 years of extended shutdown in 2002 it was decided that the reactor shutdown should be final. Preliminary decommissioning activities have been initiated by the end of 2002 under the Technical Co-operation Programme of the International Atomic Energy Agency. The objective of the project is to implement safe, timely and cost-effective decommissioning of the RA reactor up to unrestricted use of the site. Decommissioning project is closely related to two other projects: Safe Removal of the RA Reactor Spent Nuclear Fuel and Radioactive Waste Management in VINCA Institute. The main phases of the project include preparation of the detailed decommissioning plan, radiological characterization of the reactor site, dismantling and removal of the reactor components and structures, decontamination, final radiological site survey and the documentation of all the activities in order to obtain the approval for unrestricted use of the facility site. In this paper a review of the activities related to the preparation and realization of the RA reactor decommissioning project is given. Status of the project's organizational and technical aspects as for July 2004 are presented and plans for the forthcoming phases of the project realization are outlined. (author)

  10. Quantification of 235 U and 226 Ra in soil samples by means of Gamma spectroscopy

    International Nuclear Information System (INIS)

    Quintero P, E.; Rojas M, V.P.; Montes M, F.R.; Gaso P, M.I.; Cervantes N, M.L.

    2000-01-01

    In this work it is presented the Gamma Spectroscopy method which is realized in the Environmental Radiological Surveillance Laboratory using the option of deconvolution of a commercial software for the quantification of 235 U and 226 Ra; also is presented the method for the 226 Ra correction activity. (Author)

  11. Document control system as an integral part of RA documentation database application

    International Nuclear Information System (INIS)

    Steljic, M.M; Ljubenov, V.Lj. . E-mail address of corresponding author: milijanas@vin.bg.ac.yu; Steljic, M.M.)

    2005-01-01

    The decision about the final shutdown of the RA research reactor in Vinca Institute has been brought in 2002, and therefore the preparations for its decommissioning have begun. All activities are supervised by the International Atomic Energy Agency (IAEA), which also provides technical and experts' support. This paper describes the document control system is an integral part of the existing RA documentation database. (author)

  12. Up-regulation of interleukin-4 production via NF-AT/AP-1 activation in T cells by biochanin A, a phytoestrogen and its metabolites

    International Nuclear Information System (INIS)

    Park, Jin; Chung, Su Wol; Kim, Seung Hyun; Kim, Tae Sung

    2006-01-01

    Phytoestrogens are naturally occurring compounds derived from plants. Although phytoestrogens exhibit many biological functions including estrogen agonist/antagonist properties, the effect on allergic responses remains unclear. In this study, we investigated whether biochanin A, a phytoestrogen and its metabolites, genistein, p-ethylphenol and phenolic acid, affect production of IL-4, a pro-inflammatory cytokine closely associated with allergic immune responses, in primary CD4 + T cells and EL4 T lymphoma cells. Biochanin A, genistein and p-ethylphenol significantly enhanced IL-4 production from both CD4 + T cells and EL4 cells in a dose-dependent manner, while phenolic acid did not. Biochanin A, genistein and p-ethylphenol also enhanced IL-4 gene promoter activity in EL4 cells transiently transfected with IL-4 promoter constructs, but this effect was impaired in EL4 cells transfected with an IL-4 promoter construct deleted of a P4 site carrying NF-AT and AP-1 binding sites. In addition, biochanin A, genistein and p-ethylphenol increased both NF-AT and AP-1 DNA binding activities, indicating that they might enhance IL-4 production via NF-AT/AP-1 activation. Furthermore, biochanin A, genistein and p-ethylphenol increased p38 MAPK phosphorylation and PKC activity, while they did not affect ERK phosphorylation. The enhanced NF-AT DNA binding activities were suppressed by inhibitors for PI3-K and PKC, but not by p38 MAPK inhibitors. In contrast, the enhanced AP-1 DNA binding activities and p38 MAPK phosphorylation were significantly suppressed by specific inhibitors for PKC and p38 MAPK, but not by PI3-K inhibitors. These results demonstrate, for the first time, that biochanin A, genistein and p-ethylphenol enhance IL-4 production in activated T cells by two independent pathways, PI3-K/PKC/NF-AT and PKC/p38 MAPK/AP-1

  13. Secondary metabolites from Eurotium species, Aspergillus calidoustus and A. insuetus common in Canadian homes with a review of their chemistry and biological activities

    DEFF Research Database (Denmark)

    Slack, G. J.; Puniani, E.; Frisvad, Jens Christian

    2009-01-01

    As part of studies of metabolites from fungi common in the built environment in Canadian homes, we investigated metabolites from strains of three Eurotium species, namely E. herbariorum, E. amstelodami, and E. rubrum as well as a number of isolates provisionally identified as Aspergillus ustus. T...

  14. Secondary metabolites from Eurotium species, Aspergillus calidoustus and A. insuetus common in Canadian homes with a review of their chemistry and biological activities

    NARCIS (Netherlands)

    Slack, G.J.; Puniani, E.; Frisvad, J.C.; Samson, R.A.; Miller, J.D.

    2009-01-01

    As part of studies of metabolites from fungi common in the built environment in Canadian homes, we investigated metabolites from strains of three Eurotium species, namely E. herbariorum, E. amstelodami, and E. rubrum as well as a number of isolates provisionally identified as Aspergillus ustus. The

  15. Secondary metabolites from Eurotium species, Aspergillus calidoustus and A. insuetus common in Canadian homes with a review of their chemistry and biological activities.

    Science.gov (United States)

    Slack, Gregory J; Puniani, Eva; Frisvad, Jens C; Samson, Robert A; Miller, J David

    2009-04-01

    As part of studies of metabolites from fungi common in the built environment in Canadian homes, we investigated metabolites from strains of three Eurotium species, namely E. herbariorum, E. amstelodami, and E. rubrum as well as a number of isolates provisionally identified as Aspergillus ustus. The latter have been recently assigned as the new species A. insuetus and A. calidoustus. E. amstelodami produced neoechinulin A and neoechinulin B, epiheveadride, flavoglaucin, auroglaucin, and isotetrahydroauroglaucin as major metabolites. Minor metabolites included echinulin, preechinulin and neoechinulin E. E. rubrum produced all of these metabolites, but epiheveadride was detected as a minor metabolite. E. herbariorum produced cladosporin as a major metabolite, in addition to those found in E. amstelodami. This species also produced questin and neoechinulin E as minor metabolites. This is the first report of epiheveadride occurring as a natural product, and the first nonadride isolated from Eurotium species. Unlike strains from mainly infection-related samples, largely from Europe, neither ophiobolins G and H nor austins were detected in the Canadian strains of A. insuetus and A. calidoustus tested, all of which had been reported from the latter species. TMC-120 A, B, C and a sesquiterpene drimane are reported with certainty for the first time from indoor isolates, as well as two novel related methyl isoquinoline alkaloids.

  16. IL-1 receptor-antagonist (IL-1Ra) knockout mice show anxiety-like behavior by aging.

    Science.gov (United States)

    Wakabayashi, Chisato; Numakawa, Tadahiro; Odaka, Haruki; Ooshima, Yoshiko; Kiyama, Yuji; Manabe, Toshiya; Kunugi, Hiroshi; Iwakura, Yoichiro

    2015-07-10

    Interleukin 1 (IL-1) plays a critical role in stress responses, and its mRNA is induced in the brain by restraint stress. Previously, we reported that IL-1 receptor antagonist (IL-1Ra) knockout (KO) mice, which lacked IL-1Ra molecules that antagonize the IL-1 receptor, showed anti-depression-like behavior via adrenergic modulation at the age of 8 weeks. Here, we report that IL-1Ra KO mice display an anxiety-like phenotype that is induced spontaneously by aging in the elevated plus-maze (EPM) test. This anxiety-like phenotype was improved by the administration of diazepam. The expression of the anxiety-related molecule glucocorticoid receptor (GR) was significantly reduced in 20-week-old but not in 11-week-old IL-1Ra KO mice compared to wild-type (WT) littermates. The expression of the mineralocorticoid receptor (MR) was not altered between IL-1Ra KO mice and WT littermates at either 11 or 20 weeks old. Analysis of monoamine concentration in the hippocampus revealed that tryptophan, the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA), and the dopamine metabolite homovanillic acid (HVA) were significantly increased in 20-week-old IL-1Ra KO mice compared to littermate WT mice. These findings strongly suggest that the anxiety-like behavior observed in older mice was caused by the complicated alteration of monoamine metabolism and/or GR expression in the hippocampus. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Rationalization and prediction of in vivo metabolite exposures: The role of metabolite kinetics, clearance predictions and in vitro parameters

    Science.gov (United States)

    Lutz, Justin D.; Fujioka, Yasushi; Isoherranen, Nina

    2010-01-01

    Importance of the field Due to growing concerns over toxic or active metabolites, significant efforts have been focused on qualitative identification of potential in vivo metabolites from in vitro data. However, limited tools are available to quantitatively predict their human exposures. Areas covered in this review Theory of clearance predictions and metabolite kinetics is reviewed together with supporting experimental data. In vitro and in vivo data of known circulating metabolites and their parent drugs was collected and the predictions of in vivo exposures of the metabolites were evaluated. What the reader will gain The theory and data reviewed will be useful in early identification of human metabolites that will circulate at significant levels in vivo and help in designing in vivo studies that focus on characterization of metabolites. It will also assist in rationalization of metabolite-to-parent ratios used as markers of specific enzyme activity. Take home message The relative importance of a metabolite in comparison to the parent compound as well as other metabolites in vivo can only be predicted using the metabolites in vitro formation and elimination clearances, and the in vivo disposition of a metabolite can only be rationalized when the elimination pathways of that metabolite are known. PMID:20557268

  18. Determination of ''226Ra by Alpha Spectrometry by Using ''225Ra as Yield Tracer

    International Nuclear Information System (INIS)

    Crespo, M. T.; Oller, O.

    1999-01-01

    A method for the determination of low-level ''226 Ra in environmental and geological samples by alpha spectrometry is described. The method is based on the use of ''225 Ra from ''229 Th as yield tracer and has been developed to analyze U, Th and Ra in the same sample. (Author) 12 refs

  19. CDB-4124 and its putative monodemethylated metabolite, CDB-4453, are potent antiprogestins with reduced antiglucocorticoid activity: in vitro comparison to mifepristone and CDB-2914.

    Science.gov (United States)

    Attardi, Barbara J; Burgenson, Janet; Hild, Sheri A; Reel, Jerry R; Blye, Richard P

    2002-02-25

    To obtain selective antiprogestins, we have examined the in vitro antiprogestational/antiglucocorticoid properties of two novel compounds, CDB-4124 and the putative monodemethylated metabolite, CDB-4453, in transcription and receptor binding assays and compared them to CDB-2914 and mifepristone. All four antiprogestins bound with high affinity to rabbit uterine progestin receptors (PR) and recombinant human PR-A and PR-B (rhPR-A, rhPR-B) and were potent inhibitors of R5020-induced transactivation of the PRE2-tk-luciferase (PRE2-tk-LUC) reporter plasmid and endogenous alkaline phosphatase production in T47D-CO human breast cancer cells. None of these compounds exhibited agonist activity in these cells. Induction of luciferase activity was potentiated about five-fold by 8-Br-cAMP under basal conditions and to the same extent in the presence of the PR antagonists. Mifepristone bound to rabbit thymic glucocorticoid receptors (GR) with approximately twice the avidity of the CDB antiprogestins. Inhibition of GR-mediated transcription of PRE2-tk-LUC was assessed in HepG2 human hepatoblastoma cells. Mifepristone exhibited greater antiglucocorticoid activity than CDB-2914, 4124, and 4453, about 12-, 22-, and 185-fold, respectively. Thus, while there was a good correlation between binding to PR and functional activity of these antiprogestins, GR binding was not predictive of their glucocorticoid antagonist activity. In agreement with our in vivo results, CDB-4124 and CDB-4453, as well as CDB-2914, are potent antiprogestins in vitro, but show considerably less antiglucocorticoid activity than mifepristone.

  20. Peroxidase activity in roots of arracacha affected by pH and temperature = Atividade da peroxidase em raízes de batata-baroa afetada pelo pH e temperatura

    Directory of Open Access Journals (Sweden)

    Luciana Nunes Menolli

    2011-07-01

    Full Text Available In this paper, roots of arracacha (Arracacia xanthorrhyza Bancroft were stored at 5ºC to induce chilling injury symptoms and stress-related peroxidase activity. Later, peroxidase kinetic activity was determined in different pH and temperature conditions. For this, soluble crude extract was sequentially saturated with ammonium sulfate, obtaining a semi-purified enzyme solution used for the analysis. Activity of peroxidase induced by the chilling at 5oC was determined from pH 2.5 to 9.0 and at temperature ranging from 10 to80oC. The peroxidase had higher activity when the reaction occurred between pH 5.5 and 6.0 and at temperature of 30oC. Complete inactivation of the activity was observed in pH 2.5 after 60 minutes of pre-incubation or at 60oC for 10 minutes or alternatively at 70oCafter 5 minutes of pre-incubation. The enzyme is more susceptible to inactivation in acid than alkaline pHs or alternatively using heat treatment.Neste trabalho, raízes de batata-baroa (Arracacia xanthorrhiza Bancroft foram armazenadas a 5oC para induzir injúria por frio e expressar atividade da peroxidase de estresse. Posteriormente, a cinética de atividade foi determinada em diferentes condições depHs e temperatura. Para isto, extrato solúvel da raiz foi sequencialmente saturado com sulfato de amônio, obtendo-se uma preparação semi-purificada para a análise enzimática. Atividade peroxidativa induzida pela temperatura de armazenamento de 5oC foideterminada em pHs de 2,5 a 9,0 e a temperaturas de 10 a 80oC. A atividade da peroxidase foi maior quando a reação foi realizada nos pHs de 5,5 e 6,0 e temperatura de 30oC. A inativação completa da enzima ocorreu em pH de 2,5 após 60 min. de pré-incubação ou a60oC por 10 min., e alternativamente a 70oC após 5 min. de pré-incubação. A enzima foi mais susceptível à inativação em pH ácido do que alcalino, podendo também ser inativada pelo tratamento de calor.

  1. Microsomal metabolism of trenbolone acetate metabolites ...

    Science.gov (United States)

    Trenbolone acetate (TBA) is a synthetic growth promoter widely used in animal agriculture, and its metabolites are suspected endocrine disrupting compounds in agriculturally impacted receiving waters. However, beyond the three widely recognized TBA metabolites (17-trenbolone, 17-trenbolone and trendione), little is known about other metabolites formed in vivo and subsequently discharged into the environment, with some evidence suggesting these unknown metabolites comprise a majority of the TBA mass dosed to the animal. Here, we explored the metabolism of the three known TBA metabolites using rat liver microsome studies. All TBA metabolites are transformed into a complex mixture of monohydroxylated products. Based on product characterization, the majority are more polar than the parent metabolites but maintain their characteristic trienone backbone. A minor degree of interconversion between known metabolites was also observed, as were higher order hydroxylated products with a greater extent of reaction. Notably, the distribution and yield of products were generally comparable across a series of variably induced rat liver microsomes, as well as during additional studies with human and bovine liver microsomes. Bioassays conducted with mixtures of these transformation products suggest that androgen receptor (AR) binding activity is diminished as a result of the microsomal treatment, suggesting that the transformation products are generally less potent than

  2. Novel bacterial metabolite merochlorin A demonstrates in vitro activity against multi-drug resistant methicillin-resistant Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    George Sakoulas

    Full Text Available We evaluated the in vitro activity of a merochlorin A, a novel compound with a unique carbon skeleton, against a spectrum of clinically relevant bacterial pathogens and against previously characterized clinical and laboratory Staphylococcus aureus isolates with resistance to numerous antibiotics.Merochlorin A was isolated and purified from a marine-derived actinomycete strain CNH189. Susceptibility testing for merochlorin A was performed against previously characterized human pathogens using broth microdilution and agar dilution methods. Cytotoxicity was assayed in tissue culture assays at 24 and 72 hours against human HeLa and mouse sarcoma L929 cell lines.The structure of as new antibiotic, merochlorin A, was assigned by comprehensive spectroscopic analysis. Merochlorin A demonstrated in vitro activity against Gram-positive bacteria, including Clostridium dificile, but not against Gram negative bacteria. In S. aureus, susceptibility was not affected by ribosomal mutations conferring linezolid resistance, mutations in dlt or mprF conferring resistance to daptomycin, accessory gene regulator knockout mutations, or the development of the vancomycin-intermediate resistant phenotype. Merochlorin A demonstrated rapid bactericidal activity against MRSA. Activity was lost in the presence of 20% serum.The unique meroterpenoid, merochlorin A demonstrated excellent in vitro activity against S. aureus and C. dificile and did not show cross-resistance to contemporary antibiotics against Gram positive organisms. The activity was, however, markedly reduced in 20% human serum. Future directions for this compound may include evaluation for topical use, coating biomedical devices, or the pursuit of chemically modified derivatives of this compound that retain activity in the presence of serum.

  3. Bio-Activity and Dereplication-Based Discovery of Ophiobolins and Other Fungal Secondary Metabolites Targeting Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Tanja Thorskov Bladt

    2013-11-01

    Full Text Available The purpose of this study was to identify and characterize fungal natural products (NPs with in vitro bioactivity towards leukemia cells. We based our screening on a combined analytical and bio-guided approach of LC-DAD-HRMS dereplication, explorative solid-phase extraction (E-SPE, and a co-culture platform of CLL and stromal cells. A total of 289 fungal extracts were screened and we tracked the activity to single compounds in seven of the most active extracts. The novel ophiobolin U was isolated together with the known ophiobolins C, H, K as well as 6-epiophiobolins G, K and N from three fungal strains in the Aspergillus section Usti. Ophiobolins A, B, C and K displayed bioactivity towards leukemia cells with induction of apoptosis at nanomolar concentrations. The remaining ophiobolins were mainly inactive or only slightly active at micromolar concentrations. Dereplication of those ophiobolin derivatives possessing different activity in combination with structural analysis allowed a correlation of the chemical structure and conformation with the extent of bioactivity, identifying the hydroxy group at C3 and an aldehyde at C21, as well as the A/B-cis ring structure, as indispensible for the strong activity of the ophiobolins. The known compounds penicillic acid, viridicatumtoxin, calbistrin A, brefeldin A, emestrin A, and neosolaniol monoacetate were identified from the extracts and also found generally cytotoxic.

  4. Design and manufacture of a three-counter channel system based on delayed coincidence principle using for 22'3Ra and 224Ra measurements

    International Nuclear Information System (INIS)

    Tuong Thi Thu Huong; Pham Ngoc Tuan; Dang Hong Ngoc Quy; Truong Van Dat; Tran Anh Khoi; Chau Thi Nhu Quynh

    2016-01-01

    The research group has designed and fabricated a radiation detection system for measuring low activities of 223 Ra and 224 Ra in natural waters based on a design of Giffin et al (1963). Samples are obtained by adsorbing 223 Ra and 224 Ra onto a column of MnO 2 coated fiber (Mn fiber). The short-lived Rn daughters of 223 Ra and 224 Ra which recoil from the Mn fiber are swept into a scintillation detector where alpha decays of Rn and Po occur. Signals from the detector are sent to a delayed coincidence circuit which discriminates decay of the 224 Ra daughters, 220 Ra and 216 Po, from decays of the 223 Ra daughters, 219 Ra and 215 Po. The main product of this project is a “Low Alpha counting system” based on digital technology. This system consists of some main electronic circuit such as amplifier, single channel analyzer, counters/timers, micro-processor, RS232 interfacing. Almost of mentioned-above components have been designed and fabricated using ISE 10.1 software toolkits from Xilinx. The application program for controlling and collecting data from the device is written in LabView. In comparison with conventional analog circuits, the design of this system is smaller and easy to use owing to being connected to personal computer through RS232 interface in order to data acquisition and processing. This is also a new trend in the field of development of nuclear equipment with the aim to simple design, cost-saving (Reuse of hardware components can further reduce the system development cost), flexible (arbitrarily adjust measurement parameters by setting parameters from software), user-Friendly Environment (program directly embedded into the FPGA). (author)

  5. Estimation of annual effective dose from 226Ra 228Ra due to consumption of foodstuffs by inhabitants of high level natural radiation of Ramsar, Iran

    International Nuclear Information System (INIS)

    Fathivand, A.A.; Asefi, M.; Amidi, A.

    2005-01-01

    Full text: A knowledge of natural radioactivity in man and his environment is important since naturally occurring radionuclides are the major source of radiation exposure to man. Radioactive nuclides present in the natural environment enter the human body mainly through food and water.Besides, measurement of naturally occurring radionuclides in the environment can be used not only as a reference when routine releases from nuclear installation or accidental radiation exposures are assessed, but also as a baseline to evaluate the impact caused by non-nuclear activities. In Iran, measurement of natural and artificial radionuclides in environmental samples in normal and high-background radiation areas have been performed by some investigators but no information has been available on 226 Ra and 228 Ra in foodstuffs. Therefore we have started measurements of 226 Ra and 228 Ra in foodstuffs of Ramsar which is a coastal city in the north part of Iran and has been known as one of the world's high level natural radiation areas, using low level gamma spectrometry measurement system .The results from our measurements and food consumption rates for inhabitants of Ramsar city have been used for the estimation of annual effective dose due to consumption of foodstuffs by inhabitants of Ramsar city. A total of 33 samples from 11 different foodstuffs including root vegetables (beetroot), leafy vegetables (lettuce, parsley and spinach) and tea, meat,chicken, pea,broad bean, rice, and cheese were purchased from markets and were analyzed for their 226 Ra and 228 Ra concentrations. The highest concentrations of 226 Ra and 228 Ra were determined in tea samples with 1570 and 1140 mBq kg -1 respectively and the maximum estimated annual effective dose from 226 Ra and Ra due to consumption foodstuffs were determined to be 19.22 and 0.71 μSv from rice and meat samples respectively