Toxicity and physiological effects of brominated flame retardant PBDE-47 on two life stages of grass shrimp, Palaemonetes pugio.

Science.gov (United States)

Key, Peter B; Chung, Katy W; Hoguet, Jennifer; Shaddrix, Brian; Fulton, Michael H

2008-07-25

This study examined the effects of a polybrominated diphenyl ether (PBDE) compound, PBDE-47, on adult and larval stages of the estuarine grass shrimp (Palaemonetes pugio). The 96-h LC50 test resulted in an estimate of 23.60 microg/L (95% confidence interval=14.51-38.37 microg/L) for larval shrimp. Adult shrimp had a higher 96-h LC50 of 78.07 microg/L (95% CI=65.1-93.63 microg/L). Four physiological biomarkers glutathione (GSH), lipid peroxidation (LPx), cholesterol (CHL) and acetylcholinesterase (AChE) were then assessed to study the sublethal effects of PBDE-47 exposure. GSH, LPx and AChE levels in both adults and larvae were not affected by PBDE-47 at concentrations up to 50 microg/L for 96 h. CHL levels were elevated in adults and larvae at the lowest exposure concentrations tested, but significant differences were found only in adult exposures. Effects associated with PBDE-47 aqueous exposures were observed at levels well above those reported in the environment.

PBDE exposure from food in Ireland: optimising data exploitation in probabilistic exposure modelling.

Science.gov (United States)

Trudel, David; Tlustos, Christina; Von Goetz, Natalie; Scheringer, Martin; Hungerbühler, Konrad

2011-01-01

Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants added to plastics, polyurethane foam, electronics, textiles, and other products. These products release PBDEs into the indoor and outdoor environment, thus causing human exposure through food and dust. This study models PBDE dose distributions from ingestion of food for Irish adults on congener basis by using two probabilistic and one semi-deterministic method. One of the probabilistic methods was newly developed and is based on summary statistics of food consumption combined with a model generating realistic daily energy supply from food. Median (intermediate) doses of total PBDEs are in the range of 0.4-0.6 ng/kg(bw)/day for Irish adults. The 97.5th percentiles of total PBDE doses lie in a range of 1.7-2.2 ng/kg(bw)/day, which is comparable to doses derived for Belgian and Dutch adults. BDE-47 and BDE-99 were identified as the congeners contributing most to estimated intakes, accounting for more than half of the total doses. The most influential food groups contributing to this intake are lean fish and salmon which together account for about 22-25% of the total doses.

PBDE levels in human milk: the situation in Germany and potential influencing factors - a controlled study

Energy Technology Data Exchange (ETDEWEB)

Vieth, B.; Mielke, H.; Ostermann, B.; Ruediger, T. [Federal Inst. for Risk Assessment, Berlin (Germany); Herrmann, T.; Paepke, O. [ERGO Forschungsgesellschaft mbH, Hamburg (Germany)

2004-09-15

An exponential increase of PBDE levels in breast milk from Sweden between 1972 and 1997 has been reported, which is in contrast to the continuous decline of other chlorinated POPs in breast milk. Also in blood samples from Germany, an increasing trend has been observed during the period from 1985 to 1999. The knowledge about human exposure pathways, which contribute to the PBDE body burden, is very limited. Consumption of food of animal origin, inhalation or ingestion of dust and further factors possibly influencing the PBDE levels in human matrices, like age, breast-feeding or smoking are under discussion. Only a few data on PBDE levels in breast milk from Germany have been published. To fill the data gaps, a controlled study was started in 2001 to characterise the PBDE levels in human milk from Germany with special efforts to identify and quantify deca-BDE-209. Furthermore, it was intended to verify potential factors possibly influencing PBDE levels. Two main hypotheses were proposed: (1) Are PBDE levels in breast milk from mothers consuming traditional food (omnivores) higher than those found in breast milk from mothers consuming vegetarian or vegan food? and (2) Are the PBDE levels found in human milk after a three-months period of breast-feeding lower than those detected at the beginning or does breast feeding result in a lower body burden, respectively? This paper summarises preliminary results. Further analytical data and results of data evaluation will be presented at the conference.

BDE-99, but not BDE-47, is a transient aryl hydrocarbon receptor agonist in zebrafish liver cells

Energy Technology Data Exchange (ETDEWEB)

Yang, Jie; Zhu, Jinyong; Chan, King Ming, E-mail: kingchan@cuhk.edu.hk

2016-08-15

Polybrominated diphenyl ethers (PBDEs) are endocrine-disrupting chemicals that affect the environment and the health of humans and wildlife. In this study, the zebrafish liver (ZFL) cell line was used in vitro to investigate two major PBDE contaminants: 2, 2′, 4, 4′, 5-pentabromodiphenyl ether (BDE-99) and 2, 2′, 4, 4′-tetrabromodiphenyl ether (BDE-47). BDE-99 was found to significantly induce cytochrome P450 (CYP1A), uridine diphosphate glucuronosyl transferase 1 family a, b (ugt1ab), 7-ethoxyresorufin-O-deethylase activity and an aryl hydrocarbon receptor (Ahr) dependent xenobiotic response element luciferase reporter system, confirming the Ahr-mediated activation of CYP1A by BDE-99. The time-course effect indicated that the role of BDE-99 in Ahr-mediated signaling is likely to be transient and highly dependent on the ability of BDE-99 to induce CYP1A and ugt1ab, and presumably its metabolism. BDE-99 also exhibited a significant dose-response effect on a developed zebrafish pregnane X receptor luciferase reporter gene system. However, the other abundant contaminant under study, BDE-47, did not exhibit the above effects. Together, these results indicated that the molecular mechanism of PBDEs induced in ZFL cells is a chemically specific process that differs between members of the PBDE family. CYP1A induction derived by BDE-99 warrants further risk assessment as the humans, wildlife and environment are exposed to a complex mixture including dioxin-like compounds and carcinogenic compounds. - Highlights: • BDE-99 is an aryl hydrocarbon receptor (Ahr) agonist in zebrafish liver cell-line ZFL. • BDE-99 induced EROD activity, CYP1A and ugt1ab gene expression, in ZFL. • BDE-99 induced the pregnane X receptor (Pxr) luciferase reporter gene system in ZFL. • BDE-47 did not show any effects in ZFL to induce CYP1A, ugt1ab, and EROD. • BDE-47 and -99 showed no induction of Rxr and Pxr pathways in ZFL cells.

Precortical phase of Alzheimer’s disease (AD)-related tau cytoskeletal pathology

Science.gov (United States)

Stratmann, Katharina; Heinsen, Helmut; Korf, Horst-Werner; Del Turco, Domenico; Ghebremedhin, Estifanos; Seidel, Kay; Bouzrou, Mohamed; Grinberg, Lea T.; Bohl, Jürgen; Wharton, Stephen B; den Dunnen, Wilfred; Rüb, Udo

2015-01-01

coeruleus, and parabrachial nuclei) in the Braak and Braak AD stage 0 individuals and in all of these subcortical nuclei in the Braak and Braak AD stage I individuals. The widespread affection of the subcortical nuclei in our Braak and Braak AD stage I individuals shows that the extent of the subcortical tau cytoskeletal pathology in this AD stage has been considerably underestimated during the last decades. In addition, our novel findings in the Braak and Braak AD stage 0 individuals support the concept that subcortical nuclei become already affected during an early ‘pre-cortical’ evolutional phase before the first AD-related cytoskeletal changes occur in the well-known cortical predilection sites of the mediobasal temporal lobe (i.e. transentorhinal and entorhinal regions). In addition, our new findings indicate that the AD-related tau cytoskeletal pathology by no means is confined to single subcortical nuclei of Braak and Braak AD stage 0 individuals, but may develop in a large variety of their subcortical nuclei interconnected with the allocortical entorhinal and transentorhinal regions. Accordingly, these very early involved subcortical brain regions may represent the origin of the AD-related tau cytoskeletal pathology, from where the neuronal cytoskeletal pathology takes an ascending course towards the secondarily affected allocortex and spreads transneuronally along anatomical pathways and interconnectivities in predictable and stereotypical sequences PMID:26193084

Aggregatibacter actinomycetemcomitans lipopolysaccharide affects human gingival fibroblast cytoskeletal organization.

Science.gov (United States)

Gutiérrez-Venegas, Gloria; Contreras-Marmolejo, Luis Arturo; Román-Alvárez, Patricia; Barajas-Torres, Carolina

2008-04-01

The cytoskeleton is a dynamic structure that plays a key role in maintaining cell morphology and function. This study investigates the effect of bacterial wall lipopolysaccharide (LPS), a strong inflammatory agent, on the dynamics and organization of actin, tubulin, vimentin, and vinculin proteins in human gingival fibroblasts (HGF). A time-dependent study showed a noticeable change in actin architecture after 1.5 h of incubation with LPS (1 microg/ml) with the formation of orthogonal fibers and further accumulation of actin filament at the cell periphery by 24 h. When 0.01-10 microg/ml of LPS was added to human gingival fibroblast cultures, cells acquired a round, flat shape and gradually developed cytoplasmic ruffling. Lipopolysaccharides extracted from Aggregatibacter actinomycetemcomitans periodontopathogenic bacteria promoted alterations in F-actin stress fibres of human gingival cells. Normally, human gingival cells have F-actin fibres that are organized in linear distribution throughout the cells, extending along the cell's length. LPS-treated cells exhibited changes in cytoskeletal protein organization, and F-actin was reorganized by the formation of bundles underneath and parallel to the cell membrane. We also found the reorganization of the vimentin network into vimentin bundling after 1.5 h of treatment. HGF cells exhibited diffuse and granular gamma-tubulin stain. There was no change in LPS-treated HGF. However, vinculin plaques distributed in the cell body diminished after LPS treatment. We conclude that the dynamic and structured organization of cytoskeletal filaments and actin assembly in human gingival fibroblasts is altered by LPS treatment and is accompanied by a decrease in F-actin pools.

Spatial trends of polybrominated diphenyl ether (PBDE) congeners

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Spatial trends of polybrominated diphenyl ether (PBDE) congeners were analyzed in young of the year bluefish collected along the U.S. Atlantic coastline from...

Black carbon inclusive multichemical modeling of PBDE and PCB biomagnification and -transformation in estuarine food webs.

Science.gov (United States)

Di Paolo, Carolina; Gandhi, Nilima; Bhavsar, Satyendra P; Van den Heuvel-Greve, Martine; Koelmans, Albert A

2010-10-01

Bioavailability and bioaccumulation of polybrominated diphenylethers (PBDEs) are affected by adsorption on black carbon (BC) and metabolism in biota, respectively. Recent studies have addressed these two processes separately, illustrating their importance in assessing contaminant dynamics. In order to properly examine biomagnification of polychlorinated biphenyls (PCBs) and PBDEs in an estuarine food-web, here we set up a black carbon inclusive multichemical model. A dual domain sorption model, which accounted for sorption to organic matter (OM) and black carbon (BC), was used to estimate aqueous phase concentrations from the measured chemical concentrations in suspended solids. We adapted a previously published multichemical model that tracks the movement of a parent compound and its metabolites in each organism and within its food web. First, the model was calibrated for seven PCB congeners assuming negligible metabolism. Subsequently, PBDE biomagnification was modeled, including biotransformation and bioformation of PBDE congeners, keeping the other model parameters the same. The integrated model was capable of predicting trophic magnification factors (TMF) within error limits. PBDE metabolic half-lives ranged 21-415 days and agreed to literature data. The results showed importance of including BC as an adsorbing phase, and biotransformation and bioformation of PBDEs for a proper assessment of their dynamics in aquatic systems.

PBDE: Structure-Activity Studies for the Inhibition of Hepatitis C Virus NS3 Helicase

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Kazi Abdus Salam

2014-04-01

Full Text Available The helicase portion of the hepatitis C virus nonstructural protein 3 (NS3 is considered one of the most validated targets for developing direct acting antiviral agents. We isolated polybrominated diphenyl ether (PBDE 1 from a marine sponge as an NS3 helicase inhibitor. In this study, we evaluated the inhibitory effects of PBDE (1 on the essential activities of NS3 protein such as RNA helicase, ATPase, and RNA binding activities. The structure-activity relationship analysis of PBDE (1 against the HCV ATPase revealed that the biphenyl ring, bromine, and phenolic hydroxyl group on the benzene backbone might be a basic scaffold for the inhibitory potency.

PTP-PEST controls EphA3 activation and ephrin-induced cytoskeletal remodelling.

Science.gov (United States)

Mansour, Mariam; Nievergall, Eva; Gegenbauer, Kristina; Llerena, Carmen; Atapattu, Lakmali; Hallé, Maxime; Tremblay, Michel L; Janes, Peter W; Lackmann, Martin

2016-01-15

Eph receptors and their corresponding membrane-bound ephrin ligands regulate cell positioning and establish tissue patterns during embryonic and oncogenic development. Emerging evidence suggests that assembly of polymeric Eph signalling clusters relies on cytoskeletal reorganisation and underlies regulation by protein tyrosine phosphatases (PTPs). PTP-PEST (also known as PTPN12) is a central regulator of actin cytoskeletal dynamics. Here, we demonstrate that an N-terminal fragment of PTP-PEST, generated through an ephrinA5-triggered and spatially confined cleavage mediated by caspase-3, attenuates EphA3 receptor activation and its internalisation. Isolation of EphA3 receptor signalling clusters within intact plasma membrane fragments obtained by detergent-free cell fractionation reveals that stimulation of cells with ephrin triggers effective recruitment of this catalytically active truncated form of PTP-PEST together with key cytoskeletal and focal adhesion proteins. Importantly, modulation of actin polymerisation using pharmacological and dominant-negative approaches affects EphA3 phosphorylation in a similar manner to overexpression of PTP-PEST. We conclude that PTP-PEST regulates EphA3 activation both by affecting cytoskeletal remodelling and through its direct action as a PTP controlling EphA3 phosphorylation, indicating its multifaceted regulation of Eph signalling. © 2016. Published by The Company of Biologists Ltd.

Revisión global de los contaminantes emergentes PBDE y el caso particular de México

OpenAIRE

Rocha-Gutiérrez, Beatriz Adriana; Peralta-Pérez, María del Rosario; Zavala-Díaz de la Serna, Francisco Javier

2015-01-01

Los éteres de bifenilos polibromados (PBDE, por sus siglas en inglés) son un grupo específico de contaminantes emergentes que se caracterizan por ser lipofílicos, hidrofóbicos, bioacumulables y resistentes a la biodegradación. La familia de PBDE consiste de 209 isómeros o congéneres y su estructura química, persistencia y distribución en el ambiente siguen patrones muy similares a los polibromobifenilos (PBB) y a los policlorobifenilos (PCB). El uso principal de los PBDE es como retardantes d...

Highest PBDE levels (max 63 ppm) yet found in biota measured in seabird eggs from San Francisco Bay

Energy Technology Data Exchange (ETDEWEB)

She, J.; Holden, A.; Tanner, M.; Sharp, M.; Hooper, K. [Department of Toxic Substances Control, Berkeley, CA (United States). Hazardous Materials Lab.; Adelsbach, T. [Environmental Contaminants Division, Sacramento Fish and Wildlife Office, US Fish and Wildlife Service, Sacramento, CA (United States)

2004-09-15

High levels of polybrominated diphenylethers (PBDEs) have been found in humans and wildlife from the San Francisco Bay Area, with levels in women among the highest in the world, and levels in piscivorous seabird eggs at the ppm level. Seabirds are useful for monitoring and assessing ecosystem health at various times and places because they occupy a high trophic level in the marine food web, are long-lived, and are generally localized near their breeding and non-breeding sites. In collaboration with the US Fish and Wildlife Services (USFWS), we are carrying out a three-year investigation of dioxin, PCB and PBDE levels in eggs from fish-eating seabirds. Year 1 (2002) PBDE measurements from 73 bird eggs were reported at Dioxin2003. Year 2 (2003) PBDE measurements from 45 samples are presented in this report. The highest PBDE level measured in eggs was 63 ppm, lipid, which is the highest PBDE level, yet reported in biota.

Hierarchical Distribution of the Tau Cytoskeletal Pathology in the Thalamus of Alzheimer's Disease Patients.

Science.gov (United States)

Rüb, Udo; Stratmann, Katharina; Heinsen, Helmut; Del Turco, Domenico; Ghebremedhin, Estifanos; Seidel, Kay; den Dunnen, Wilfred; Korf, Horst-Werner

2016-01-01

In spite of considerable progress in neuropathological research on Alzheimer's disease (AD), knowledge regarding the exact pathoanatomical distribution of the tau cytoskeletal pathology in the thalamus of AD patients in the advanced Braak and Braak AD stages V or VI of the cortical cytoskeletal pathology is still fragmentary. Investigation of serial 100 μm-thick brain tissue sections through the thalamus of clinically diagnosed AD patients with Braak and Braak AD stage V or VI cytoskeletal pathologies immunostained with the anti-tau AT8 antibody, along with the affection of the extraterritorial reticular nucleus of the thalamus, reveals a consistent and severe tau immunoreactive cytoskeletal pathology in the limbic nuclei of the thalamus (e.g., paraventricular, anterodorsal and laterodorsal nuclei, limitans-suprageniculate complex). The thalamic nuclei integrated into the associative networks of the human brain (e.g., ventral anterior and mediodorsal nuclei) are only mildly affected, while its motor precerebellar (ventral lateral nucleus) and sensory nuclei (e.g., lateral and medial geniculate bodies, ventral posterior medial and lateral nuclei, parvocellular part of the ventral posterior medial nucleus) are more or less spared. The highly stereotypical and characteristic thalamic distribution pattern of the AD-related tau cytoskeletal pathology represents an anatomical mirror of the hierarchical topographic distribution of the cytoskeletal pathology in the interconnected regions of the cerebral cortex of AD patients. These pathoanatomical parallels support the pathophysiological concept of a transneuronal spread of the disease process of AD along anatomical pathways. The AD-related tau cytoskeletal pathology in the thalamus most likely contributes substantially to the neuropsychiatric disease symptoms (e.g., dementia), attention deficits, oculomotor dysfunctions, altered non-discriminative aspects of pain experience of AD patients, and the disruption of their

Regulation of cytoskeletal organization by syndecan transmembrane proteoglycans

DEFF Research Database (Denmark)

Yoneda, Atsuko; Couchman, John R

2003-01-01

have recently suggested that signaling through core protein of syndecans can regulate cytoskeletal organization through their clustering, association with cytoskeletal structures, binding to cytoplasmic binding proteins, and intracellular phosphorylation. Here we will review current understanding...... of signaling through syndecans in cytoskeletal organization....

Thyroid hormone levels and hepatic enzyme activity in lactating dams after gestational exposure to low dose PBDE 47

Energy Technology Data Exchange (ETDEWEB)

Kuriyama, S.N.; Grande, S.W.; Akkoc, Z.; Souza, C.A.M. de; Chahoud, I. [Charite Univ. Medical School Berlin (Germany). Inst. of Clinical Pharmacology and Toxicology, Dept. Toxicology, Campus Benjamin Franklin; Fidalgo-Neto, A.A. [Oswaldo Cruz Foundation, Rio de Janeiro (Brazil). Lab. of Environmental Toxicology

2004-09-15

Polybrominated diphenyl ethers (PBDEs), a class of widely used flame retardants, are found extensively in the environment (shown by several studies on sentinel animal species), as well as in humans. In rodents, technical commercial PBDE mixtures and individual congeners have shown to interfere with thyroid hormone homeostasis, produce a mix-type induction of hepatic microsomal enzymes, disrupt spontaneous behaviour, impair learning and memory and alter the cholinergic transmitter system. In rat and mice, some technical PBDE commercial mixtures such as DE-71 and Bromkal 70 and the congener PBDE 47 have shown to decrease circulating thyroid hormone levels. PBDEs are also able to induce both hepatic phase I and phase II detoxification enzymes, demonstrated by several investigations in laboratory animals. For example, induction of ethoxyresorufin-O-deethylase (EROD), pentoxyresorufin-Odespenthylase (PROD) and uridinediphospho-glucuronosyltransferase (UDPGT) has been shown in rodents and cell lines after exposure to technical mixtures or individual congeners. However, these studies deal with doses much higher than that found in human tissues, highlighting the importance of assessing the adverse effects of doses close to human exposure levels. PBDE 47 is the most predominant congener found in environmental and human samples (including human milk) and, therefore, hazard identification is extremely important for human risk assessment. We administered a single dose to gravid dams on gestation day 6 of either 140 {mu}g/kg BW or 700 {mu}g/kg BW of the congener, 2,2'4,4'-tetrabromo diphenyl ether (PBDE 47). These doses are pertinent to human exposure levels because a study by She et al. found a mean level of 33.3 {mu}g PBDE 47 /kg fat in human breast adipose tissue with a range from 7.01 to 196 {mu}g PBDE 47 /kg fat. In this study, thyroid hormone levels and hepatic enzyme activity were evaluated in lactating dams after in utero administration of low dose PBDE 47.

Mertk deficiency affects macrophage directional migration via disruption of cytoskeletal organization.

Directory of Open Access Journals (Sweden)

Yong Tang

Full Text Available Mertk belongs to the Tyro3, Axl and Mertk (TAM family of receptor tyrosine kinases, and plays a pivotal role in regulation of cytoskeletal rearrangement during phagocytosis. Phagocytosis by either professional or non-professional phagocytes is impaired in the Mertk deficient individual. In the present study, we further investigated the effects of Mertk mutation on peritoneal macrophage morphology, attachment, spreading and movement. Mertk-mutated macrophages exhibited decreased attachment, weak spreading, loss of spindle-like body shape and lack of clear leading and trailing edges within the first few hours of culture, as observed by environmental scanning electron microscopy. Time-lapse video photography recording showed that macrophage without Mertk conducted mainly random movement with oscillating swing around the cell body, and lost the directional migration action seen on the WT cells. Western blotting showed a decreased phosphorylation of focal adhesion kinase (FAK. Immunocytochemistry revealed that actin filaments and dynamic protein myosin II failed to concentrate in the leading edge of migrating cells. Microtubules were localized mainly in one side of mutant cell body, with no clear MTOC and associated radially-distributed microtubule bundles, which were clearly evident in the WT cells. Our results suggest that Mertk deficiency affects not only phagocytosis but also cell shape and migration, likely through a common regulatory mechanism on cytoskeletons.

Levels and distribution of polybrominated diphenyl ethers (PBDEs) in the freshwater environment surrounding a PBDE manufacturing plant in China

International Nuclear Information System (INIS)

Xu Jie; Gao Zishen; Xian Qiming; Yu Hongxia; Feng Jianfang

2009-01-01

Polybrominated diphenyl ethers (PBDEs) were determined in muscle, liver and eggs of freshwater fishes and surface sediments from the Nongkang River in Jinhu, Jiangsu Province, China. The present study is the first to report PBDE concentrations in the freshwater environment surrounding a PBDE manufacturing plant in China. The concentrations of 13 PBDE congeners in muscle, liver and eggs of freshwater fishes ranged from < LOD to 130, < LOD to 252 and < LOD to 33.3 ng/g lipid wt, respectively, while the concentrations of 13 PBDE congeners in surface sediments from sewage outfall, upstream and downstream of the river were 52, 9.2, 7.1 ng/g organic carbon wt, respectively. Contamination by PBDEs in this area was not serious when compared with other regions of the world. A relatively high proportion of BDE-183 was found, consistent with the octa-BDE technical mixtures from the manufacturing plant by the side of the river. - The first study to report concentrations of PBDEs in the freshwater environment surrounding a PBDE manufacturing plant in China.

Study of the toxic effects of flame retardant PBDE-47 on the clam Chamelea gallina (Linnaeus, 1758

Directory of Open Access Journals (Sweden)

Salvatora Angela Angioni

2013-03-01

Full Text Available The purpose of the study is to evaluate the effects of 2,2',4,4'-tetrabromodiphenylether (PBDE-47 on the Chamelea gallina clam (according to current commercial regulations: Venus gallina. PBDEs, which are used as flame retardants in various industrial products, are classed as hazardous substances by Directive 2011/65/EU. They are bioaccumulative compounds, considered to be endocrine disruptors, genotoxic, neurotoxic and practically ubiquitous, and their concentration in the environment has considerably increased in recent years. The aim of this study is to establish the effects of PBDE-47 on Chamelea gallina: toxic power and any harmful effects on the gonads, bioaccumulation capacity in the tissues, and possible entry into the food chain. The research used 96-hour and 21-day experimental tests on clams housed in filtered seawater. The tests were preceded by a period of acclimatisation of the molluscs lasting five to seven days. The clams were fed on seaweed (Dunaliella tertiolecta. The choice of the toxic compound PBDE-47 was based on the high concentration, among the congeners of PBDE, found in some aquatic species. The study demonstrated that the concentration of the contaminant used did not alter the vital functions, cause significant levels of mortality or lead to evident alteration in the gonads of Chamelea gallina. However, the research demonstrated the bioaccumulation capacity of the bivalve mollusc, allowing PBDE-47 to enter the food chain.

Cytoskeletal defects in Bmpr2-associated pulmonary arterial hypertension.

Science.gov (United States)

Johnson, Jennifer A; Hemnes, Anna R; Perrien, Daniel S; Schuster, Manfred; Robinson, Linda J; Gladson, Santhi; Loibner, Hans; Bai, Susan; Blackwell, Tom R; Tada, Yuji; Harral, Julie W; Talati, Megha; Lane, Kirk B; Fagan, Karen A; West, James

2012-03-01

The heritable form of pulmonary arterial hypertension (PAH) is typically caused by a mutation in bone morphogenic protein receptor type 2 (BMPR2), and mice expressing Bmpr2 mutations develop PAH with features similar to human disease. BMPR2 is known to interact with the cytoskeleton, and human array studies in PAH patients confirm alterations in cytoskeletal pathways. The goal of this study was to evaluate cytoskeletal defects in BMPR2-associated PAH. Expression arrays on our Bmpr2 mutant mouse lungs revealed cytoskeletal defects as a prominent molecular consequence of universal expression of a Bmpr2 mutation (Rosa26-Bmpr2(R899X)). Pulmonary microvascular endothelial cells cultured from these mice have histological and functional cytoskeletal defects. Stable transfection of different BMPR2 mutations into pulmonary microvascular endothelial cells revealed that cytoskeletal defects are common to multiple BMPR2 mutations and are associated with activation of the Rho GTPase, Rac1. Rac1 defects are corrected in cell culture and in vivo through administration of exogenous recombinant human angiotensin-converting enzyme 2 (rhACE2). rhACE2 reverses 77% of gene expression changes in Rosa26-Bmpr2(R899X) transgenic mice, in particular, correcting defects in cytoskeletal function. Administration of rhACE2 to Rosa26-Bmpr2(R899X) mice with established PAH normalizes pulmonary pressures. Together, these findings suggest that cytoskeletal function is central to the development of BMPR2-associated PAH and that intervention against cytoskeletal defects may reverse established disease.

Vertical distribution of archaeal communities associated with anaerobic degradation of pentabromodiphenyl ether (BDE-99) in river-based groundwater recharge with reclaimed water.

Science.gov (United States)

Yan, Yulin; Ma, Mengsi; Liu, Xiang; Ma, Weifang; Li, Yangyao

2018-02-01

When groundwater is recharged with reclaimed water, the presence of trace amounts of biorefractory pentabromodiphenyl ether (PBDE, specifically BDE-99) might cause potential groundwater pollution. A laboratory-scale column was designed to investigate the distribution of the community of archaea in this scenario and the associated anaerobic degradation of BDE-99. The concentration of BDE-99 decreased significantly as soil depth increased, and fluorescence in situ hybridization (FISH) analysis suggested that archaea exerted significant effects on the biodegradation of PBDE. Through 454 pyrosequencing of 16s rRNA genes, we found that the distribution and structure of the archaeal community associated with anaerobic degradation of BDE-99 in the river-based aquifer media changed significantly between different soil depths. The primary debrominated metabolites varied with changes in the vertically distributed archaeal community. The archaea in the surface layer were dominated by Methanomethylovorans, and the middle layer was mainly composed of Nitrososphaera. Nitrosopumilus and Nitrososphaera were equally abundant in the bottom layer. In addition, Methanomethylovorans abundance depended on the depth of soil, and the relative abundance of Nitrosopumilus increased with increasing depth, which was associated with the oxidation-reduction potential and the content of intermediate metabolites. We propose that Nitrososphaera and Nitrosopumilus might be the key archaeal taxa mediating the biodegradation of BDE-99.

Advances in the study of current-use non-PBDE brominated flame retardants and dechlorane plus in the environment and humans

Institute of Scientific and Technical Information of China (English)

无

2010-01-01

The fate of the high production volume,currently in use,and not regulated non-polybrominated diphenyl ether(PBDE) flame retardants,such as tetrabromobisphenol A(TBBPA) ,hexabromocyclododecane(HBCD) and dechlorane plus(DP),and the alternative flame retardants of PBDE,such as BTBPE and DBDPE,in the environment has attracted increasing attention and aroused concern due to the increasing regulation and phasing-out of PBDEs.This paper reviews the distribution,bioaccumulation,human exposure and environmental behavior of those non-PBDE flame retardants in various environmental compartments.The data gaps and needs for future research are discussed.

Biotechnological aspects of cytoskeletal regulation in plants.

Science.gov (United States)

Komis, George; Luptovciak, Ivan; Doskocilova, Anna; Samaj, Jozef

2015-11-01

The cytoskeleton is a protein-based intracellular superstructure that evolved early after the appearance of bacterial prokaryotes. Eventually cytoskeletal proteins and their macromolecular assemblies were established in eukaryotes and assumed critical roles in cell movements, intracellular organization, cell division and cell differentiation. In biomedicine the small-molecules targeting cytoskeletal elements are in the frontline of anticancer research with plant-derived cytoskeletal drugs such as Vinca alkaloids and toxoids, being routinely used in the clinical practice. Moreover, plants are also major material, food and energy resources for human activities ranging from agriculture, textile industry, carpentry, energy production and new material development to name some few. Most of these inheritable traits are associated with cell wall synthesis and chemical modification during primary and secondary plant growth and inevitably are associated with the dynamics, organization and interactions of the plant cytoskeleton. Taking into account the vast intracellular spread of microtubules and actin microfilaments the cytoskeleton collectively assumed central roles in plant growth and development, in determining the physical stance of plants against the forces of nature and becoming a battleground between pathogenic invaders and the defense mechanisms of plant cells. This review aims to address the role of the plant cytoskeleton in manageable features of plants including cellulose biosynthesis with implications in wood and fiber properties, in biofuel production and the contribution of plant cytoskeletal elements in plant defense responses against pathogens or detrimental environmental conditions. Ultimately the present work surveys the potential of cytoskeletal proteins as platforms of plant genetic engineering, nominating certain cytoskeletal proteins as vectors of favorable traits in crops and other economically important plants. Copyright © 2015 Elsevier Inc. All

Integrated in silico and in vivo approaches to investigate effects of BDE-99 mediated by the nuclear receptors on developing zebrafish.

Science.gov (United States)

Zhang, Li; Jin, Yaru; Han, Zhihua; Liu, Hongling; Shi, Laihao; Hua, Xiaoxue; Doering, Jon A; Tang, Song; Giesy, John P; Yu, Hongxia

2018-03-01

One of the most abundant polybrominated diphenyl ethers (PBDEs) is 2,2',4,4',5-pentabromodiphenyl ether (BDE-99), which persists and potentially bioaccumulates in aquatic wildlife. Previous studies in mammals have shown that BDE-99 affects development and disrupts certain endocrine functions through signaling pathways mediated by nuclear receptors. However, fewer studies have investigated the potential of BDE-99 to interact with nuclear receptors in aquatic vertebrates such as fish. In the present study, interactions between BDE-99 and nuclear receptors were investigated by in silico and in vivo approaches. This PBDE was able to dock into the ligand-binding domain of zebrafish aryl hydrocarbon receptor 2 (AhR2) and pregnane X receptor (PXR). It had a significant effect on the transcriptional profiles of genes associated with AhR or PXR. Based on the developed cytoscape of all zebrafish genes, it was also inferred that AhR and PXR could interact via cross-talk. In addition, both the in silico and in vivo approaches found that BDE-99 affected peroxisome proliferator-activated receptor alpha (PPARα), glucocorticoid receptor, and thyroid receptor. Collectively, our results demonstrate for the first time detailed in silico evidence that BDE-99 can bind to and interact with zebrafish AhR and PXR. These findings can be used to elaborate the molecular mechanism of BDE-99 and guide more objective environmental risk assessments. Environ Toxicol Chem 2018;37:780-787. © 2017 SETAC. © 2017 SETAC.

Placental transfer of the polybrominated diphenyl ethers BDE-47, BDE-99 and BDE-209 in a human placenta perfusion system: an experimental study

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Frederiksen Marie

2010-07-01

Full Text Available Abstract Background Polybrominated diphenyl ethers (PBDEs have been widely used as flame retardants in consumer products. PBDEs may affect thyroid hormone homeostasis, which can result in irreversible damage of cognitive performance, motor skills and altered behaviour. Thus, in utero exposure is of very high concern due to critical windows in fetal development. Methods A human ex vivo placenta perfusion system was used to study the kinetics and extent of the placental transfer of BDE-47, BDE-99 and BDE-209 during four-hour perfusions. The PBDEs were added to the maternal circulation and monitored in the maternal and fetal compartments. In addition, the perfused cotyledon, the surrounding placental tissue as well as pre-perfusion placental tissue and umbilical cord plasma were also analysed. The PBDE analysis included Soxhlet extraction, clean-up by adsorption chromatography and GC-MS analysis. Results and Discussion Placental transfer of BDE-47 was faster and more extensive than for BDE-99. The fetal-maternal ratios (FM-ratio after four hours of perfusion were 0.47 and 0.25 for BDE-47 and BDE-99, respectively, while the indicative permeability coefficient (IPC measured after 60 minutes of perfusion was 0.26 h-1 and 0.10 h-1, respectively. The transport of BDE-209 seemed to be limited. These differences between the congeners may be related to the degree of bromination. Significant accumulation was observed for all congeners in the perfused cotyledon as well as in the surrounding placental tissue. Conclusion The transport of BDE-47 and BDE-99 indicates in utero exposure to these congeners. Although the transport of BDE-209 was limited, however, possible metabolic debromination may lead to products which are both more toxic and transportable. Our study demonstrates fetal exposure to PBDEs, which should be included in risk assessment of PBDE exposure of women of child-bearing age.

Effects of developmental exposure to a Commercial PBDE mixture (DE-71) on protein networks in the rat Cerebellum and Hippocampus

Science.gov (United States)

Title (20 words): Effects of developmental exposure to a Commercial PBDE mixture (DE-71) on protein networks in the rat Cerebellum and Hippocampus. Introduction (120 words): Polybrominated diphenyl ethers (PBDE5) possess neurotoxic effects similar to those of PCBs. The cellular a...

PCB and PBDE levels in a highly threatened dolphin species from the Southeastern Brazilian coast

International Nuclear Information System (INIS)

Lavandier, Ricardo; Arêas, Jennifer; Quinete, Natalia; Moura, Jailson F. de; Taniguchi, Satie; Montone, Rosalinda; Siciliano, Salvatore; Moreira, Isabel

2016-01-01

In the Northern coast of Rio de Janeiro State is located the major urban centers of the oil and gas industry of Brazil. The intense urbanization in recent decades caused an increase in human use of the coastal areas, which is constantly impacted by agricultural, industrial and wastewater discharges. Franciscana dolphin (Pontoporia blainvillei) is a small cetacean that inhabits coastal regions down to a 30 m depth. This species is considered the most threatened cetacean in the Western South Atlantic Ocean. This study investigated the levels of 52 PCB congeners and 9 PBDE congeners in liver of nine individuals found stranded or accidentally caught between 2011 and 2012 in the Northern coast of Rio de Janeiro. PCB mean levels ranged from 208 to 5543 ng g"−"1 lw and PBDEs mean concentrations varied between 13.84 and 36.94 ng g"−"1 lw. Contamination patterns suggest the previous use of Aroclor 1254, 1260 and penta-BDE mixtures in Brazil. While still few studies have assessed the organic contamination in cetaceans from the Southern Hemisphere, including Brazil, the levels found in this study could represent a health risk to these endangered species. - Highlights: • PCBs and PBDEs were measured in liver samples from Franciscana dolphins. • BDE 47, 99 and 100 were found in all individuals samples. • PCB-153, 138 and 180 were the major PCB congeners detected. • Results suggest the existence of PCBs and PBDEs contamination sources in Brazil. • PCBs and PDBEs levels could represent a risk to these endangered dolphin species. - PCB and PBDE concentrations found in Franciscana dolphins suggest the presence of contamination sources in Southeastern Brazil and could represent a high health risk to these endangered species.

Use of wild trout for PBDE assessment in freshwater environments: Review and summary of critical factors

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Juan M. Ríos

2015-11-01

Full Text Available Certain wild animals represent sentinels to address issues related to environmental pollution, since they can provide integrative data on both pollutant exposure and biological effects. Despite their technological benefits, PBDEs are considered a threat to environmental health due to their persistence, toxicity, and capacity to be accumulated. These pollutants have been found geographically widespread in fish, particularly in predator species such as trout. The aim of this work is to critically review the applicability and usefulness of wild trout for assessing PBDEs in freshwater environments. Reviewed reports include data from highly industrialized areas as well as areas from remote regions with relatively low human activity, including European and North American great lakes and freshwater environments in Europe, Greenland, subarctic areas and Patagonia, respectively. A summary of relevant factors were grouped into organism-specific factors (food habits, age, size, lipid content, sex and reproduction, tissue type, mechanism of contaminant uptake and metabolism, and PBDE levels in the surrounding environment (sediment. Five wild trout species [rainbow trout (Oncorhynchus mykiss, brown trout (Salmo trutta, lake trout (Salvelinus namaycush, arctic char (Salvelinus alpinus, and brook trout (Salvelinus fontinalis], collected worldwide within the 1994 to present time frame, were considered. Multivariate techniques (principal component analysis-PCA and mapping approach, showed clear differences in geographic distribution patterns of PBDE levels in trout depending on the region studied: wild trout from European and North American great lakes have the highest PBDE loads. This pattern could be due to high industrial activity at these locations. A correlational approach used to explore intraspecific relationships between PBDE levels and morphometry, showed positive relationships only for brown trout. Further, brown trout showed the highest trout

Comparative developmental neurotoxicity of flame-retardants, polybrominated flame-retardants and organophosphorous compounds, in mice

Energy Technology Data Exchange (ETDEWEB)

Eriksson, P.; Johansson, N.; Viberg, H.; Fischer, C.; Fredriksson, A. [Dept. of Environmental Toxicology, Uppsala Univ. (Sweden)

2004-09-15

Recently we have reported that certain PBDEs, such as 2,2',4,4'-tetrabromodiphenyl ether (PBDE 47), 2,2',4,4',5- pentabromodiphenyl ether (PBDE 99), 2,2',4,4',5,5'-hexabromodiphenyl ether (PBDE153) and 2,2',3,3',4,4',5,5',6,6'-decabromodiphenyl ether (PBDE 209) can cause developmental neurotoxic effects when given to neonatal mice. The developmental neurotoxic effects after neonatal exposure to PBDE 209 are suggested to be caused by a metabolite (possible de-brominated one). Neonatal exposure HBCDD has also been shown to cause developmental neurotoxic effects. Neonatal exposure to PBDE 99, PBDE 153 and HBCDD was also found to affect learning and memory in the adult animal. The induction of permanent aberration in spontaneous behaviour was induced during limited period of the neonatal brain development. The altered spontaneous behaviour was also seen to worsen with age. In these studies we have also found that the cholinergic system is one target that is affected, observed as changes in the response of the cholinergic system and a decrease in cholinergic receptors, and is one of the mechanisms underlying the observed behavioural changes. BFRs so far studied TBBPA appears not to cause developmental neurotoxic effects when administered at the same dose levels to neonatal mice. In the present studies we have investigated whether neonatal exposure to three highly brominated dipehenyl ethers, 2,2',3,4,4',5',6'-heptabromodiphenyl ether (PBDE183), 2,2',3'4'4',5,5',6- octabromodiphenyl ether (PBDE 203) and 2,2',3,3',4,4',5',6'-nonabromodiphenyl ether (PBDE 206) can induce developmental neurotoxic effects, such as aberrations in spontaneous behaviour and in learning and memory. Furthermore, neonatal developmental neurotoxicity effects were also studied for two OPs used as FR, triphenyl phosphate and tris(2-chloro-ethyl)phosphate.

Cellular automata in cytoskeletal lattices

Energy Technology Data Exchange (ETDEWEB)

Smith, S A; Watt, R C; Hameroff, S R

1984-01-01

Cellular automata (CA) activities could mediate biological regulation and information processing via nonlinear electrodynamic effects in cytoskeletal lattice arrays. Frohlich coherent oscillations and other nonlinear mechanisms may effect discrete 10/sup -10/ to 10/sup -11/ s interval events which result in dynamic patterns in biolattices such as cylindrical protein polymers: microtubules (MT). Structural geometry and electrostatic forces of MT subunit dipole oscillations suggest neighbor rules among the hexagonally packed protein subunits. Computer simulations using these suggested rules and MT structural geometry demonstrate CA activities including dynamical and stable self-organizing patterns, oscillators, and traveling gliders. CA activities in MT and other cytoskeletal lattices may have important biological regulatory functions. 23 references, 6 figures, 1 table.

PBDE and PCB levels correlated in wild caught and farm-raised fish fillets in the USA

Energy Technology Data Exchange (ETDEWEB)

Hayward, D.; Wong, J.; Krynitsky, A. [US Food and Drug Administration, College Park (United States)

2004-09-15

Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are two classes of industrial chemicals that have been widely used in the manufacture of many materials found commonly in highly industrial societies. PCBs used as an electrical insulator and in plastics have been banned in the US since 1977. PCB levels have steadily declined in foods. PBDEs are currently used as effective flame retardant in electronics, automobiles, home furnishings, textiles and in building materials. Environmental levels have not reached equilibrium. Both classes are ubiquitous contaminants with a strong tendency for bioaccumulation. The detection of PBDEs in human and some animal fats and fish/shellfish has been reported1. Recent reports of PBDEs in the US population have reported PBDE levels higher than most other industrialized countries. The pathway of these exposures is not precisely known, but one likely pathway is food. US FDA is planning to monitor some PBDE congeners beginning 2005. Data collection will begin with fish and shellfish and most likely be expanded to other foods. Fish/shellfish are already being monitored for PCDD/F and some PCB content. Several different instrumental approaches have been used successfully to measure PBDEs in human tissues and in environmental media including HRGC/HRMS, ECNI-LRMS, EI-LRMS and tandem mass spectrometry. The focus of this study is to determine PBDE levels in fish that are already known to have higher levels of PCBs relative to other fish or other foods. EI-LRMS was selected for initial testing with PBDE measurements in fish for its simplicity and availability in every FDA field laboratory.

BDE-99 (2,2',4,4',5-pentabromodiphenyl ether) triggers epithelial-mesenchymal transition in colorectal cancer cells via PI3K/Akt/Snail signaling pathway.

Science.gov (United States)

Wang, Fei; Ruan, Xin-Jian; Zhang, Hong-Yan

2015-01-01

The gut is in direct contact with BDE-99 (2,2',4,4',5-pentabromodiphenyl ether), one of the most abundant PBDE congeners in the environment and in human tissues. The objective of the present study was to investigate the effects of BDE-99 on colorectal cancer (CRC) cells. The effects of BDE-99 on cell proliferation were measured by CCK-8 assay in the CRC cell line HCT-116. Wound healing and transwell migration/invasion assays were used to test the migration and invasion of CRC cells. Factors related to epithelial-to-mesenchymal transition (EMT) were measured by real-time PCR and Western blot analysis for mRNA and protein levels, respectively. BDE-99 was found to increase migration and invasion and trigger EMT in HCT-116 cells; EMT was characterized by cells acquiring mesenchymal spindle-like morphology and by increased expression of N-cadherin with a concomitant decrease in E-cadherin. BDE-99 treatment also increased the protein and mRNA levels of the transcription factor Snail, but not Slug, Twist, and ZEB1. Knockdown of Snail by siRNA significantly attenuated BDE-99-induced EMT in HCT-116 cells, suggesting that Snail plays a crucial role in BDE-99-induced EMT. The PI3K/Akt inhibitor LY294002 completely blocked BDE-99-induced Snail and invasion of HCT-116 cells. Our results revealed that BDE-99 can trigger the EMT of colon cancer cells via the PI3K/AKT/Snail signaling pathway. This study provides new insight into the tumorigenesis and metastasis of CRC stimulated by BDE-99 and possibly other PBDE congeners.

Cooperation of the BTB-Zinc finger protein, Abrupt, with cytoskeletal regulators in Drosophila epithelial tumorigenesis

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Nezaket Turkel

2015-08-01

Full Text Available The deregulation of cell polarity or cytoskeletal regulators is a common occurrence in human epithelial cancers. Moreover, there is accumulating evidence in human epithelial cancer that BTB-ZF genes, such as Bcl6 and ZBTB7A, are oncogenic. From our previous studies in the vinegar fly, Drosophila melanogaster, we have identified a cooperative interaction between a mutation in the apico-basal cell polarity regulator Scribble (Scrib and overexpression of the BTB-ZF protein Abrupt (Ab. Herein, we show that co-expression of ab with actin cytoskeletal regulators, RhoGEF2 or Src64B, in the developing eye-antennal epithelial tissue results in the formation of overgrown amorphous tumours, whereas ab and DRac1 co-expression leads to non-cell autonomous overgrowth. Together with ab, these genes affect the expression of differentiation genes, resulting in tumours locked in a progenitor cell fate. Finally, we show that the expression of two mammalian genes related to ab, Bcl6 and ZBTB7A, which are oncogenes in mammalian epithelial cancers, significantly correlate with the upregulation of cytoskeletal genes or downregulation of apico-basal cell polarity neoplastic tumour suppressor genes in colorectal, lung and other human epithelial cancers. Altogether, this analysis has revealed that upregulation of cytoskeletal regulators cooperate with Abrupt in Drosophila epithelial tumorigenesis, and that high expression of human BTB-ZF genes, Bcl6 and ZBTB7A, shows significant correlations with cytoskeletal and cell polarity gene expression in specific epithelial tumour types. This highlights the need for further investigation of the cooperation between these genes in mammalian systems.

Effect of polybrominated diphenyl ether (PBDE) treatment on the composition and function of the bacterial community in the sponge Haliclona cymaeformis.

KAUST Repository

Tian, Ren-Mao

2014-01-01

Marine sponges play important roles in benthic environments and are sensitive to environmental stresses. Polybrominated diphenyl ethers (PBDEs) have been widely used as flame retardants since the 1970s and are cytotoxic and genotoxic to organisms. In the present study, we studied the short-period effect of PBDE-47 (2,2\\',4,4\\'-tetrabromodiphenyl ether) treatment on the community structure and functional gene composition of the bacterial community inhabiting the marine sponge Haliclona cymaeformis. Our results showed that the bacterial community shifted from an autotrophic bacteria-dominated community to a heterotrophic bacteria-dominated community in response to PBDE-47 in a time- and concentration-dependent manner. A potentially symbiotic sulfur-oxidizing bacterium (SOB) was dominant (>80% in abundance) in the untreated sponge. However, exposure to a high concentration (1 μg/L) of PBDE-47 caused a substantial decrease in the potential symbiont and an enrichment of heterotrophic bacteria like Clostridium. A metagenomic analysis showed a selective effect of the high concentration treatment on the functional gene composition of the enriched heterotrophic bacteria, revealing an enrichment for the functions responsible for DNA repair, multidrug efflux pumping, and bacterial chemotaxis and motility. This study demonstrated that PBDE-47 induced a shift in the composition of the community and functional genes in the sponge-associated bacterial community, revealing the selective effect of PBDE-47 treatment on the functions of the bacterial community in the microenvironment of the sponge.

Comparative study of cyanotoxins affecting cytoskeletal and chromatin structures in CHO-K1 cells.

Science.gov (United States)

Gácsi, Mariann; Antal, Otilia; Vasas, Gábor; Máthé, Csaba; Borbély, György; Saker, Martin L; Gyori, János; Farkas, Anna; Vehovszky, Agnes; Bánfalvi, Gáspár

2009-06-01

In this study we compared the effects of the two frequently occuring and most dangerous cyanobacterial toxins on the cellular organization of microfilaments, microtubules and on the chromatin structure in Chinese hamster ovary (CHO-K1) cells. These compounds are the widely known microcystin-LR (MC-LR) and cylindrospermopsin (CYN) classified as the highest-priority cyanotoxin. Toxic effects were tested in a concentration and time dependent manner. The hepatotoxic MC-LR did not cause significant cytotoxicity on CHO-K1 cells under 20 microM, but caused apoptotic changes at higher concentrations. Apoptotic shrinkage was associated with the shortening and loss of actin filaments and with a concentration dependent depolymerization of microtubules. No necrosis was observed over the concentration range (1-50 microM MC-LR) tested. Cylindrospermopsin did cause apoptosis at low concentrations (1-2 microM) and over short exposure periods (12h). Necrosis was observed at higher concentrations (5-10 microM) and following longer exposure periods (24 or 48h). Cyanotoxins also affected the chromatin structure. The condensation process was inhibited by MC-LR at a later stage and manifested as broken elongated prechromosomes. CYN inhibited chromatin condensation at the early fibrillary stage leading to blurred fluorescent images of apoptotic bodies and preventing the formation of metaphase chromosomes. Cylindrospermopsin exhibited a more pronounced toxic effect causing cytoskeletal and nuclear changes as well as apoptotic and necrotic alterations.

Cadmium-induced glutathionylation of actin occurs through a ROS-independent mechanism: Implications for cytoskeletal integrity

Energy Technology Data Exchange (ETDEWEB)

Choong, Grace; Liu, Ying; Xiao, Weiqun; Templeton, Douglas M., E-mail: doug.templeton@utoronto.ca

2013-10-15

Cadmium disrupts the actin cytoskeleton in rat mesangial cells, and we have previously shown that this involves a complex interplay involving activation of kinase signaling, protein translocation, and disruption of focal adhesions. Here we investigate the role that glutathionylation of actin plays in Cd{sup 2+}-associated cytoskeletal reorganization. Low concentrations of Cd{sup 2+} (0.5–2 μM) caused an increase in actin glutathionylation by 6 h, whereas at higher concentrations glutathionylation remained at basal levels. Although oxidation with diamide increased glutathionylation, reactive oxygen species (ROS) were not involved in the Cd{sup 2+}-dependent effect, as only Cd{sup 2+} concentrations above 2 μM were sufficient to increase ROS. However, low [Cd{sup 2+}] increased total glutathione levels without affecting the ratio of reduced/oxidized glutathione, and inhibition of glutathione synthesis suppressed actin glutathionylation. Cadmium increased the activity of the enzyme glutaredoxin, which influences the equilibrium between glutathionylated and deglutathionylated proteins and thus may influence levels of glutathionylated actin. Together these observations show that cadmium-dependent effects on actin glutathionylation are affected by glutathione metabolism and not by direct effects of ROS on thiol chemistry. In vitro polymerization assays with glutathionylated actin show a decreased rate of polymerization. In contrast, immunofluorescence of cytoskeletal structure in intact cells suggests that increases in actin glutathionylation accompanying increased glutathione levels occurring under low Cd{sup 2+} exposure are protective in vivo, with cytoskeletal disruption ensuing only when higher Cd{sup 2+} concentrations increase ROS levels and prevent an increase in actin–glutathione conjugates. - Highlights: • Cadmium disrupts the actin cytoskeleton in mesangial cells. • Cadmium induces glutathionylation of actin at low concentrations. �

Cadmium-induced glutathionylation of actin occurs through a ROS-independent mechanism: Implications for cytoskeletal integrity

International Nuclear Information System (INIS)

Choong, Grace; Liu, Ying; Xiao, Weiqun; Templeton, Douglas M.

2013-01-01

Cadmium disrupts the actin cytoskeleton in rat mesangial cells, and we have previously shown that this involves a complex interplay involving activation of kinase signaling, protein translocation, and disruption of focal adhesions. Here we investigate the role that glutathionylation of actin plays in Cd 2+ -associated cytoskeletal reorganization. Low concentrations of Cd 2+ (0.5–2 μM) caused an increase in actin glutathionylation by 6 h, whereas at higher concentrations glutathionylation remained at basal levels. Although oxidation with diamide increased glutathionylation, reactive oxygen species (ROS) were not involved in the Cd 2+ -dependent effect, as only Cd 2+ concentrations above 2 μM were sufficient to increase ROS. However, low [Cd 2+ ] increased total glutathione levels without affecting the ratio of reduced/oxidized glutathione, and inhibition of glutathione synthesis suppressed actin glutathionylation. Cadmium increased the activity of the enzyme glutaredoxin, which influences the equilibrium between glutathionylated and deglutathionylated proteins and thus may influence levels of glutathionylated actin. Together these observations show that cadmium-dependent effects on actin glutathionylation are affected by glutathione metabolism and not by direct effects of ROS on thiol chemistry. In vitro polymerization assays with glutathionylated actin show a decreased rate of polymerization. In contrast, immunofluorescence of cytoskeletal structure in intact cells suggests that increases in actin glutathionylation accompanying increased glutathione levels occurring under low Cd 2+ exposure are protective in vivo, with cytoskeletal disruption ensuing only when higher Cd 2+ concentrations increase ROS levels and prevent an increase in actin–glutathione conjugates. - Highlights: • Cadmium disrupts the actin cytoskeleton in mesangial cells. • Cadmium induces glutathionylation of actin at low concentrations. • Glutathionylation requires glutathione

Time trends of polybrominated diphenyl ethers in East China Seas: Response to the booming of PBDE pollution industry in China.

Science.gov (United States)

Li, Yuanyuan; Lin, Tian; Hu, Limin; Feng, Jialiang; Guo, Zhigang

2016-01-01

The East China Seas (ECSs) are the receptors of the land-based persistent organic pollutants (POPs), such as polybrominated diphenyl ethers (PBDEs) mainly from China through atmospheric deposition driven by the East Asian winter monsoon and fluvial discharge (e.g., Yangtze River and Yellow River), making the offshore sediments to be a good proxy to reconstruct history of those pollutants in China. In this work, four well-placed sediment cores were extracted from the mud areas in the ECSs, and the (210)Pb-dated cores were analyzed to yield historical concentration profiles of PBDEs in the area. The results showed that there was a persistent increase from 1970s and almost no clear sign in the decline of PBDEs until recently in China. More importantly, there was a faster increase of PBDEs from 1990s in China; while this period was just shown as gradually leveling off or even declining trends in developed countries. The persistently increasing trend of PBDEs in China since 1990s could be largely due to the booming of the manufacturing industry and unexpectedly transfer of PBDE pollution from developed countries to China. Besides, the relative high concentrations and fluxes of PBDEs in the core from coastal ECS located near a well-known electrical/electronic waste (e-waste) recycling area suggests an important contribution of PBDE emissions from recycling centers of e-waste in China. Although efforts in environmental monitoring of PBDE contamination have been substantially increased over the last decade, China is still lagging behind in terms of nationwide regulation of PBDE usage and treatment of disposal PBDE-containing products. Copyright © 2016 Elsevier Ltd. All rights reserved.

Occurrence and fate of PBDE in sewage sludge from municipal waste water treatment plants

Energy Technology Data Exchange (ETDEWEB)

Knoth, W.; Mann, W.; Meyer, R.; Nebhuth, J. [Federal Environmental Agency, POP Laboratory, Langen (Germany)

2004-09-15

With the rapidly growing use of combustible polymer material, e.g. for IT/TV casings, mattresses, upholstered furniture, the use of flame retardants like polybrominated diphenyl ether (PBDE) has also increased strongly. PBDE are available as three commercial mixtures of BDE congeners named after their principal component: PeBDE, OcBDE and DeBDE. They can release into the environment during their production, use or after disposal and have become ubiquitous. Because of (exponentially) increasing levels of the main congeners of technical Pe- and OcBDE in human blood and milk in Europe and California, the use and the placing on the market of preparations and articles containing these two flame retardants in concentrations >0.1% by mass are prohibited from August 15, 2004 in the European Union4 and in California from the year 2008. The main North American manufacturer of PeBDE flame retardant will voluntarily cease production by the end of 2004. For DeBDE a risk assessment is in progress. Surprising high levels were analysed in blood samples from 155 volunteers in the UK2 and a debromination to more bioavailable Hx- and HpBDE by juvenile carp (cyprinus carpio) following dietary exposure was observed. The objective of this study is to get more information about the actual levels and time trend of PBDE in sewage sludge in Germany and on a possible degradation of DeBDE by photolytic or reductive debromination during waste water treatment process.

Bar-coded pyrosequencing reveals the responses of PBDE-degrading microbial communities to electron donor amendments.

Directory of Open Access Journals (Sweden)

Meiying Xu

Full Text Available Polybrominated diphenyl ethers (PBDEs can be reductively degraded by microorganisms under anaerobic conditions. However, little is known about the effect of electron donors on microbial communities involved in PBDEs degradation. Here we employed 454 Titanium pyrosequencing to examine the phylogenetic diversity, composition, structure and dynamics of microbial communities from microcosms under the conditions of different electron donor amendments. The community structures in each of the five alternate electron donor enrichments were significantly shifted in comparison with those of the control microcosm. Commonly existing OTUs between the treatment and control consortia increased from 5 to 17 and more than 50% of OTUs increased around 13.7 to 186 times at least in one of the microcosms after 90-days enrichment. Although the microbial communities at different taxonomic levels were significantly changed by different environmental variable groups in redundancy analysis, significant correlations were observed between the microbial communities and PBDE congener profiles. The lesser-brominated PBDE congeners, tri-BDE congener (BDE-32 and hexa-BDE, were identified as the key factors shaping the microbial community structures at OTU level. Some rare populations, including the known dechlorinating bacterium, Dehalobacter, showed significant positive-correlation with the amounts of PBDE congeners in the consortia. The same results were also observed on some unclassified bacteria. These results suggest that PBDEs-degrading microbial communities can be successfully enriched, and their structures and compositions can be manipulated through adjusting the environmental parameters.

The autonomic higher order processing nuclei of the lower brain stem are among the early targets of the Alzheimer's disease-related cytoskeletal pathology.

Science.gov (United States)

Rüb, U; Del Tredici, K; Schultz, C; Thal, D R; Braak, E; Braak, H

2001-06-01

The nuclei of the pontine parabrachial region (medial parabrachial nucleus, MPB; lateral parabrachial nucleus, LPB; subpeduncular nucleus, SPP) together with the intermediate zone of the medullary reticular formation (IRZ) are pivotal relay stations within central autonomic regulatory feedback systems. This study was undertaken to investigate the evolution of the Alzheimer's disease-related cytoskeletal pathology in these four sites of the lower brain stem. We examined the MPB, LPB, SPP and IRZ in 27 autopsy cases and classified the cortical Alzheimer-related cytoskeletal anomalies according to an established staging system (neurofibrillary tangle/neuropil threads [NFT/NT] stages I-VI). The lesions were visualized either with the antibody AT8, which is immunospecific for the abnormally phosphorylated form of the cytoskeletal protein tau, or with a modified Gallyas silver iodide stain. The MPB, SPB, and IRZ display cytoskeletal pathology in stage I and the LPB in stage II, whereby bothstages correspond to the preclinical phase of Alzheimer's disease (AD). In stages III-IV (incipient AD), the MPB and SPP are severely affected. In all of the stage III-IV cases, the lesions in the LPB and IRZ are well developed. In stages V and VI (clinical phase of AD), the MPB and SPP are filled with the abnormal intraneuronal material. At stages V-VI, the LPB is moderately involved and the IRZ shows severe damage. The pathogenesis of the AD-related cytoskeletal lesions in the nuclei of the pontine parabrachial region and in the IRZ conforms with the cortical NFT/NT staging sequence I-VI. In the event that the cytoskeletal pathology observed in this study impairs the function of the nerve cells involved, it is conceivable that autonomic mechanisms progressively deteriorate with advancing cortical NFT/NT stages. This relationship remains to be established, but it could provide insights into the illusive correlation between the AD-related cytoskeletal pathology and the function of

Assembly of the MreB-associated cytoskeletal ring of Escherichia coli.

Science.gov (United States)

Vats, Purva; Shih, Yu-Ling; Rothfield, Lawrence

2009-04-01

The Escherichia coli actin homologue MreB is part of a helical cytoskeletal structure that winds around the cell between the two poles. It has been shown that MreB redistributes during the cell cycle to form circumferential ring structures that flank the cytokinetic FtsZ ring and appear to be associated with division and segregation of the helical cytoskeleton. We show here that the MreB cytoskeletal ring also contains the MreC, MreD, Pbp2 and RodA proteins. Assembly of MreB, MreC, MreD and Pbp2 into the ring structure required the FtsZ ring but no other known components of the cell division machinery, whereas assembly of RodA into the cytoskeletal ring required one or more additional septasomal components. Strikingly, MreB, MreC, MreD and RodA were each able to independently assemble into the cytoskeletal ring and coiled cytoskeletal structures in the absence of any of the other ring components. This excludes the possibility that one or more of these proteins acts as a scaffold for incorporation of the other proteins into these structures. In contrast, incorporation of Pbp2 required the presence of MreC, which may provide a docking site for Pbp2 entry.

Fate, partitioning, and mass loading of polybrominated diphenyl ethers (PBDEs) during the treatment processing of municipal sewage.

Science.gov (United States)

Song, Min; Chu, Shaogang; Letcher, Robert J; Seth, Rajesh

2006-10-15

Sewage treatment plant (STP) effluents are likely a major source of contamination for PBDEs, especially in the receiving water bodies of local aquatic environments surrounding the location of these discharges. Congeners of the pentaBDE mixture, 2,2,',4,4'-tetrabromodiphenyl ether (BDE47), 2,2,',4,4',5-pentabromodiphenyl ether (BDE99), 2,2,',4,4',6-pentabromodiphenyl ether (BDE100), 2,2,',4,4',5,5'-hexabromodiphenyl ether (BDE153), and 2,2,',4,4',5,6'-hexabromodiphenyl ether (BDE154), are of great environmental concern in North America due to their persistence, potential for bioaccumulation, and >97% use of the global production of the mixture in the region. Detailed characterization of the distribution of eight PBDE congeners (2,4,4'-tribromoDE (BDE28) and BDE47, 99, 100, 138, 153, 154, and 183) was carried out at five sites along the treatment process at an activated sludge-type secondary treatment municipal STP facility. PentaBDE mixture congeners, sigma5PBDE (sum of BDE47, 99, 100, 153, and 154) accounted for >98% of the total (sigma 8) PBDE concentration at all sites, with over 80% of the composition being BDE47 and BDE99. Presence of dissolved organic matter affected the mobility of PBDEs during the initial stages of the treatment process. About 9% of the influent mass of sigma5PBDE to the facility is estimated to be discharged into the Little River (leading to the Detroit River) with the final effluent, resulting in an estimated mass loading of approximately 0.7 kg/year. The total mass loading of sigma5PBDE to the Detroit River is expected to be much larger as effluent from this facility accounts for <10% of the total STP discharges to the river.

Progressive supranuclear palsy: neuronal and glial cytoskeletal pathology in the higher order processing autonomic nuclei of the lower brainstem.

Science.gov (United States)

Rüb, U; Del Tredici, K; Schultz, C; de Vos, R A I; Jansen Steur, E N H; Arai, K; Braak, H

2002-02-01

The medial and lateral parabrachial nuclei (MPB, LPB), the gigantocellular reticular nucleus (GI), the raphes magnus (RMG) and raphes obscurus nuclei (ROB), as well as the intermediate reticular zone (IRZ) represent pivotal subordinate brainstem centres, all of which control autonomic functions. In this study, we investigated the occurrence and severity of the neuronal and glial cytoskeletal pathology in these six brainstem nuclei from 17 individuals with clinically diagnosed and neuropathologically confirmed progressive supranuclear palsy (PSP). The association between the severity of the pathology and the duration of the disease was investigated by means of correlation analysis. The brainstem nuclei in all of the PSP cases were affected by the neuronal cytoskeletal pathology, with the IRZ and GI regularly showing severe involvement, the MPB, RMG, and ROB marked involvement, and the LPB mild involvement. In the six nuclear greys studied, glial cells undergo alterations of their cytoskeleton on an irregular basis, whereby diseased oligodendrocytes predominantly presented as coiled bodies and affected astrocytes as thorn-shaped astrocytes. In all six nuclei, the severity of the neuronal or glial cytoskeletal pathology showed no correlation with the duration of PSP. In view of their functional role, the neuronal pathology in the nuclei studied offers a possible explanation for the autonomic dysfunctions that eventually develop in the course of PSP.

Placental transfer of the polybrominated diphenyl ethers BDE-47, BDE-99 and BDE-209 in a human placenta perfusion system: an experimental study

DEFF Research Database (Denmark)

Frederiksen, Marie; Vorkamp, Katrin; Mathiesen, Line

2010-01-01

high concern due to critical windows in fetal development. METHODS: A human ex vivo placenta perfusion system was used to study the kinetics and extent of the placental transfer of BDE-47, BDE-99 and BDE-209 during four-hour perfusions. The PBDEs were added to the maternal circulation and monitored...... should be included in risk assessment of PBDE exposure of women of child-bearing age....

Abnormal expression of leiomyoma cytoskeletal proteins involved in cell migration.

Science.gov (United States)

Ura, Blendi; Scrimin, Federica; Arrigoni, Giorgio; Athanasakis, Emmanouil; Aloisio, Michelangelo; Monasta, Lorenzo; Ricci, Giuseppe

2016-05-01

Uterine leiomyomas are monoclonal tumors. Several factors are involved in the neoplastic transformation of the myometrium. In our study we focused on dysregulated cytoskeletal proteins in the leiomyoma as compared to the myometrium. Paired tissue samples of ten leiomyomas and adjacent myometria were obtained and analyzed by two‑dimensional gel electrophoresis (2-DE). Mass spectrometry was used for protein identification, and western blotting for 2-DE data validation. The values of ten cytoskeletal proteins were found to be significantly different: eight proteins were upregulated in the leiomyoma and two proteins were downregulated. Three of the upregulated proteins (myosin regulatory light polypeptide 9, four and a half LIM domains protein 1 and LIM and SH3 domain protein 1) are involved in cell migration, while downregulated protein transgelin is involved in replicative senescence. Myosin regulatory light polypeptide 9 (MYL9) was further validated by western blotting because it is considered to be a cell migration marker in several cancers and could play a key role in leiomyoma development. Our data demonstrate significant alterations in the expression of cytoskeletal proteins involved in leiomyoma growth. A better understanding of the involvement of cytoskeletal proteins in leiomyoma pathogenesis may contribute to the identification of new therapeutic targets and the development of new pharmacological approaches.

Exposure assessment of French women and their newborn to brominated flame retardants: Determination of tri- to deca- polybromodiphenylethers (PBDE) in maternal adipose tissue, serum, breast milk and cord serum

International Nuclear Information System (INIS)

Antignac, Jean-Philippe; Cariou, Ronan; Zalko, Daniel; Berrebi, Alain; Cravedi, Jean-Pierre; Maume, Daniel; Marchand, Philippe; Monteau, Fabrice; Riu, Anne; Andre, Francois; Le Bizec, Bruno

2009-01-01

In the frame of a French monitoring program, tri- to deca- polybromodiphenylethers (PBDE) have been measured in maternal and cord serum, adipose tissue, and breast milk samples, collected from 93 volunteer women during caesarean deliveries. The seven major tri- to heptaBDE (BDE-28, 47, 99, 100, 153, 154, and 183) were detected in adipose tissue and breast milk with cumulated median values of 2.59 and 2.51 ng g -1 l w. Nine highly brominated octa- to decaBDE (BDE-196, 197, 201, 202, 203, 206, 207, 208 and 209) was performed in the same samples, with cumulated median values of 2.73 and 3.39 ng g -1 l w in adipose tissue and breast milk, respectively. At this opposite, median levels of octa- to decaBDE in maternal and cord serum appeared significantly higher than the levels of tri- to heptaBDE in the same matrices, i.e. 8.85 and 12.34 versus 0.98 and 0.69 ng g -1 l w, respectively. - This study provides the first data at the French level regarding the occurrence of PBDE in human, and demonstrates the exposure of both human foetus at late stage of pregnancy and newborn at early stages of life through breastfeeding with special emphasis on the presence of highly brominated compounds

Exposure assessment of French women and their newborn to brominated flame retardants: Determination of tri- to deca- polybromodiphenylethers (PBDE) in maternal adipose tissue, serum, breast milk and cord serum

Energy Technology Data Exchange (ETDEWEB)

Antignac, Jean-Philippe [Laboratoire d' Etude des Residus et Contaminants dans les Aliments (LABERCA), USC INRA 2013, Ecole Nationale Veterinaire de Nantes (ENVN), Route de Gachet, BP 50707, 44307 Nantes Cedex 3 (France)], E-mail: antignac@vet-nantes.fr; Cariou, Ronan [Laboratoire d' Etude des Residus et Contaminants dans les Aliments (LABERCA), USC INRA 2013, Ecole Nationale Veterinaire de Nantes (ENVN), Route de Gachet, BP 50707, 44307 Nantes Cedex 3 (France); Zalko, Daniel [UMR 1089 Xenobiotiques, INRA, 31931 Toulouse (France); Berrebi, Alain [Centre Hospitalier Universitaire de Toulouse, Hopital Paule de Viguier, Service de gynecologie-obstetrique, Toulouse (France); Cravedi, Jean-Pierre [UMR 1089 Xenobiotiques, INRA, 31931 Toulouse (France); Maume, Daniel; Marchand, Philippe; Monteau, Fabrice [Laboratoire d' Etude des Residus et Contaminants dans les Aliments (LABERCA), USC INRA 2013, Ecole Nationale Veterinaire de Nantes (ENVN), Route de Gachet, BP 50707, 44307 Nantes Cedex 3 (France); Riu, Anne [Unite Signalisation Hormonale, Environnement et Cancer, U824 INSERM, 34298 Montpellier Cedex 5 (France); Andre, Francois; Le Bizec, Bruno [Laboratoire d' Etude des Residus et Contaminants dans les Aliments (LABERCA), USC INRA 2013, Ecole Nationale Veterinaire de Nantes (ENVN), Route de Gachet, BP 50707, 44307 Nantes Cedex 3 (France)

2009-01-15

In the frame of a French monitoring program, tri- to deca- polybromodiphenylethers (PBDE) have been measured in maternal and cord serum, adipose tissue, and breast milk samples, collected from 93 volunteer women during caesarean deliveries. The seven major tri- to heptaBDE (BDE-28, 47, 99, 100, 153, 154, and 183) were detected in adipose tissue and breast milk with cumulated median values of 2.59 and 2.51 ng g{sup -1} l w. Nine highly brominated octa- to decaBDE (BDE-196, 197, 201, 202, 203, 206, 207, 208 and 209) was performed in the same samples, with cumulated median values of 2.73 and 3.39 ng g{sup -1} l w in adipose tissue and breast milk, respectively. At this opposite, median levels of octa- to decaBDE in maternal and cord serum appeared significantly higher than the levels of tri- to heptaBDE in the same matrices, i.e. 8.85 and 12.34 versus 0.98 and 0.69 ng g{sup -1} l w, respectively. - This study provides the first data at the French level regarding the occurrence of PBDE in human, and demonstrates the exposure of both human foetus at late stage of pregnancy and newborn at early stages of life through breastfeeding with special emphasis on the presence of highly brominated compounds.

Nucleocytoplasmic Shuttling of Cytoskeletal Proteins: Molecular Mechanism and Biological Significance

Directory of Open Access Journals (Sweden)

Masahiro Kumeta

2012-01-01

Full Text Available Various nuclear functional complexes contain cytoskeletal proteins as regulatory subunits; for example, nuclear actin participates in transcriptional complexes, and actin-related proteins are integral to chromatin remodeling complexes. Nuclear complexes such as these are involved in both basal and adaptive nuclear functions. In addition to nuclear import via classical nuclear transport pathways or passive diffusion, some large cytoskeletal proteins spontaneously migrate into the nucleus in a karyopherin-independent manner. The balance of nucleocytoplasmic distribution of such proteins can be altered by several factors, such as import versus export, or capture and release by complexes. The resulting accumulation or depletion of the nuclear populations thereby enhances or attenuates their nuclear functions. We propose that such molecular dynamics constitute a form of cytoskeleton-modulated regulation of nuclear functions which is mediated by the translocation of cytoskeletal components in and out of the nucleus.

Selective ablation of the androgen receptor in mouse sertoli cells affects sertoli cell maturation, barrier formation and cytoskeletal development.

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Ariane Willems

2010-11-01

Full Text Available The observation that mice with a selective ablation of the androgen receptor (AR in Sertoli cells (SC (SCARKO mice display a complete block in meiosis supports the contention that SC play a pivotal role in the control of germ cell development by androgens. To delineate the physiological and molecular mechanism responsible for this control, we compared tubular development in pubertal SCARKO mice and littermate controls. Particular attention was paid to differences in SC maturation, SC barrier formation and cytoskeletal organization and to the molecular mediators potentially involved. Functional analysis of SC barrier development by hypertonic perfusion and lanthanum permeation techniques and immunohistochemical analysis of junction formation showed that SCARKO mice still attempt to produce a barrier separating basal and adluminal compartment but that barrier formation is delayed and defective. Defective barrier formation was accompanied by disturbances in SC nuclear maturation (immature shape, absence of prominent, tripartite nucleoli and SC polarization (aberrant positioning of SC nuclei and cytoskeletal elements such as vimentin. Quantitative RT-PCR was used to study the transcript levels of genes potentially related to the described phenomena between day 8 and 35. Differences in the expression of SC genes known to play a role in junction formation could be shown from day 8 for Cldn11, from day 15 for Cldn3 and Espn, from day 20 for Cdh2 and Jam3 and from day 35 for ZO-1. Marked differences were also noted in the transcript levels of several genes that are also related to cell adhesion and cytoskeletal dynamics but that have not yet been studied in SC (Actn3, Ank3, Anxa9, Scin, Emb, Mpzl2. It is concluded that absence of a functional AR in SC impedes the remodeling of testicular tubules expected at the onset of spermatogenesis and interferes with the creation of the specific environment needed for germ cell development.

Interplay between cytoskeletal stresses and cell adaptation under chronic flow.

Directory of Open Access Journals (Sweden)

Deepika Verma

Full Text Available Using stress sensitive FRET sensors we have measured cytoskeletal stresses in α-actinin and the associated reorganization of the actin cytoskeleton in cells subjected to chronic shear stress. We show that long-term shear stress reduces the average actinin stress and this effect is reversible with removal of flow. The flow-induced changes in cytoskeletal stresses are found to be dynamic, involving a transient decrease in stress (phase-I, a short-term increase (3-6 min (Phase-II, followed by a longer-term decrease that reaches a minimum in ~20 min (Phase-III, before saturating. These changes are accompanied by reorganization of the actin cytoskeleton from parallel F-actin bundles to peripheral bundles. Blocking mechanosensitive ion channels (MSCs with Gd(3+ and GsMTx4 (a specific inhibitor eliminated the changes in cytoskeletal stress and the corresponding actin reorganization, indicating that Ca(2+ permeable MSCs participate in the signaling cascades. This study shows that shear stress induced cell adaptation is mediated via MSCs.

Effects of coexisting BDE-47 on the migration and biodegradation of BDE-99 in river-based aquifer media recharged with reclaimed water.

Science.gov (United States)

Yan, Y; Li, Y; Ma, M; Ma, W; Cheng, X; Xu, K

2018-02-01

Two prominent polybrominated diphenyl ether (PBDE) congeners have been included in the persistent organic pollutant list, 2,2',4,4',5-tetrabromodiphenyl ether (BDE-99) and 2,2,4,4'-tetrabromodiphenyl ether (BDE-47), which have been detected in treated municipal wastewater, river water, and sediments in China. A lab-scale column experiment was established to investigate the effects of the competitive sorption of BDE-47 on BDE-99 biodegradation and migration in two types of river-based aquifer soils during groundwater recharge with reclaimed water. Two types of recharge columns were used, filled with either silty clay (SC) or black carbon-amended silty clay (BCA). The decay rate constants of BDE-99 in the BCA and SC systems were 0.186 and 0.13 m -1 in the single-solute system and 0.128 and 0.071 m -1 in the binary-solute system, respectively, showing that the decay of BDE-99 was inhibited by the coexistence of BDE-47. This was particularly evident in the SC system because the higher hydrophobicity of BDE-99 determined the higher affinity and competition for sorption sites onto black carbon. The biodegradation of BDE-99 was suppressed by the coexistence of BDE-47, especially in the SC system. Lesser-brominated congeners (BDE-47 and BDE-28) and higher-brominated congeners (BDE-100, BDE-153, BDE-154, and BDE-183) were generated in the four recharge systems, albeit at different ratios. Bacterial biodiversity was influenced by the presence of BDE-47 in the SC system, while it had no significant effect on the BCA system, because the high sorption capacity of black carbon on the hydrophobic PBDEs effectively reduced their toxicity. The ranking order of the most abundant classes changed markedly due to the coexistence of BDE-47 in both the SC and BCA systems. The ranking order of the most abundant genera changed from Azospira, Methylotenera, Desulfovibrio, Methylibium, and Bradyrhizobium to Halomonas, Hyphomicrobium, Pseudomonas, Methylophaga, and Shewanella, which could

Distribution of BDE-99 and effects on metamorphosis of BDE-99 and -47 after oral exposure in Xenopus tropicalis

Energy Technology Data Exchange (ETDEWEB)

Carlsson, Gunnar [Division of Pathology, Pharmacology and Toxicology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, P.O. Box 7028, SE-750 07 Uppsala (Sweden) and Centre for Reproductive Biology in Uppsala (CRU), P.O. Box 7054, SE-750 07 Uppsala (Sweden)]. E-mail: gunnar.carlsson@bvf.slu.se; Kulkarni, Pushkar [Division of Pathology, Pharmacology and Toxicology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, P.O. Box 7028, SE-750 07 Uppsala (Sweden); Larsson, Pia [Division of Pathology, Pharmacology and Toxicology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, P.O. Box 7028, SE-750 07 Uppsala (Sweden); Norrgren, Leif [Division of Pathology, Pharmacology and Toxicology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, P.O. Box 7028, SE-750 07 Uppsala (Sweden); Centre for Reproductive Biology in Uppsala (CRU), P.O. Box 7054, SE-750 07 Uppsala (Sweden)

2007-08-15

The high concentrations of polybrominated diphenylethers (PBDEs) in the environment have raised the need for generating more information about the impact of these substances on animals. To study the distribution of {sup 14}C-labelled 2,2',4,4',5-pentabromodiphenyl ether ({sup 14}C-BDE-99) in Xenopus tropicalis (West African clawed frog) {sup 14}C-BDE-99 was administered by dietary exposure to tadpoles at stage 54 or to juvenile frogs at stage 66. Whole-body autoradiography and liquid scintillation counting were used to examine the distribution of the substance at different survival times. Further, X. tropicalis tadpoles were dietarily exposed to the PBDE congeners BDE-47 and BDE-99 to study the effects on metamorphosis process. Measurements like body weight, body length, hind limb length and developmental stage as well as histological measurements on thyroid glands were performed after 14 days of exposure. Autoradiograms revealed high concentrations and long term retention of {sup 14}C-BDE-99 in adipose tissue and melanin in frogs exposed both as tadpoles and juveniles. Further, a difference in uptake was recorded between the exposures at stages 54 and 66, implying that the juvenile frogs have higher uptake and more prolonged retention of the chemical than the tadpoles. Hind limb length was reduced in tadpoles dietarily exposed to 1 mg/g feed of both BDE congeners. This was associated with reduced body weight and body length for BDE-47, suggesting general toxicity. Tadpoles exposed to BDE-99 also showed lower developmental stage but no effects on body weight or body length, suggesting possible thyroid hormone disruption. Higher concentrations of both congeners caused increased mortality. Thus, it can be concluded that in the present study, BDE-99 was retained for a longer period in the juvenile frogs than in metamorphosing tadpoles and that BDE-99 had an impact on X. tropicalis metamorphosis that might be of thyroid disrupting origin.

Distribution of BDE-99 and effects on metamorphosis of BDE-99 and -47 after oral exposure in Xenopus tropicalis

International Nuclear Information System (INIS)

Carlsson, Gunnar; Kulkarni, Pushkar; Larsson, Pia; Norrgren, Leif

2007-01-01

The high concentrations of polybrominated diphenylethers (PBDEs) in the environment have raised the need for generating more information about the impact of these substances on animals. To study the distribution of 14 C-labelled 2,2',4,4',5-pentabromodiphenyl ether ( 14 C-BDE-99) in Xenopus tropicalis (West African clawed frog) 14 C-BDE-99 was administered by dietary exposure to tadpoles at stage 54 or to juvenile frogs at stage 66. Whole-body autoradiography and liquid scintillation counting were used to examine the distribution of the substance at different survival times. Further, X. tropicalis tadpoles were dietarily exposed to the PBDE congeners BDE-47 and BDE-99 to study the effects on metamorphosis process. Measurements like body weight, body length, hind limb length and developmental stage as well as histological measurements on thyroid glands were performed after 14 days of exposure. Autoradiograms revealed high concentrations and long term retention of 14 C-BDE-99 in adipose tissue and melanin in frogs exposed both as tadpoles and juveniles. Further, a difference in uptake was recorded between the exposures at stages 54 and 66, implying that the juvenile frogs have higher uptake and more prolonged retention of the chemical than the tadpoles. Hind limb length was reduced in tadpoles dietarily exposed to 1 mg/g feed of both BDE congeners. This was associated with reduced body weight and body length for BDE-47, suggesting general toxicity. Tadpoles exposed to BDE-99 also showed lower developmental stage but no effects on body weight or body length, suggesting possible thyroid hormone disruption. Higher concentrations of both congeners caused increased mortality. Thus, it can be concluded that in the present study, BDE-99 was retained for a longer period in the juvenile frogs than in metamorphosing tadpoles and that BDE-99 had an impact on X. tropicalis metamorphosis that might be of thyroid disrupting origin

Changes in cytoskeletal dynamics and nonlinear rheology with metastatic ability in cancer cell lines

International Nuclear Information System (INIS)

Coughlin, Mark F; Fredberg, Jeffrey J

2013-01-01

Metastatic outcome is impacted by the biophysical state of the primary tumor cell. To determine if changes in cancer cell biophysical properties facilitate metastasis, we quantified cytoskeletal biophysics in well-characterized human skin, bladder, prostate and kidney cell line pairs that differ in metastatic ability. Using magnetic twisting cytometry with optical detection, cytoskeletal dynamics was observed through spontaneous motion of surface bound marker beads and nonlinear rheology was characterized through large amplitude forced oscillations of probe beads. Measurements of cytoskeletal dynamics and nonlinear rheology differed between strongly and weakly metastatic cells. However, no set of biophysical parameters changed systematically with metastatic ability across all cell lines. Compared to their weakly metastatic counterparts, the strongly metastatic kidney cancer cells exhibited both increased cytoskeletal dynamics and stiffness at large deformation which are thought to facilitate the process of vascular invasion. (paper)

Cytoskeletal-assisted dynamics of the mitochondrial reticulum in living cells.

Science.gov (United States)

Knowles, Michelle K; Guenza, Marina G; Capaldi, Roderick A; Marcus, Andrew H

2002-11-12

Subcellular organelle dynamics are strongly influenced by interactions with cytoskeletal filaments and their associated motor proteins, and lead to complex multiexponential relaxations that occur over a wide range of spatial and temporal scales. Here we report spatio-temporal measurements of the fluctuations of the mitochondrial reticulum in osteosarcoma cells by using Fourier imaging correlation spectroscopy, over time and distance scales of 10(-2) to 10(3) s and 0.5-2.5 microm. We show that the method allows a more complete description of mitochondrial dynamics, through the time- and length-scale-dependent collective diffusion coefficient D(k,tau), than available by other means. Addition of either nocodazole to disrupt microtubules or cytochalasin D to disassemble microfilaments simplifies the intermediate scattering function. When both drugs are used, the reticulum morphology of mitochondria is retained even though the cytoskeletal elements have been de-polymerized. The dynamics of the organelle are then primarily diffusive and can be modeled as a collection of friction points interconnected by elastic springs. This study quantitatively characterizes organelle dynamics in terms of collective cytoskeletal interactions in living cells.

Hierarchical Distribution of the Tau Cytoskeletal Pathology in the Thalamus of Alzheimer's Disease Patients

NARCIS (Netherlands)

Rueb, Udo; Stratmann, Katharina; Heinsen, Helmut; Del Turco, Domenico; Ghebremedhin, Estifanos; Seidel, Kay; den Dunnen, Wilfred; Korf, Horst-Werner

2015-01-01

In spite of considerable progress in neuropathological research on Alzheimer's disease (AD), knowledge regarding the exact pathoanatomical distribution of the tau cytoskeletal pathology in the thalamus of AD patients in the advanced Braak and Braak AD stages V or VI of the cortical cytoskeletal

Zearalenone altered the cytoskeletal structure via ER stress- autophagy- oxidative stress pathway in mouse TM4 Sertoli cells.

Science.gov (United States)

Zheng, Wanglong; Wang, Bingjie; Si, Mengxue; Zou, Hui; Song, Ruilong; Gu, Jianhong; Yuan, Yan; Liu, Xuezhong; Zhu, Guoqiang; Bai, Jianfa; Bian, Jianchun; Liu, ZongPing

2018-02-20

The aim of this study was to investigate the molecular mechanisms of the destruction of cytoskeletal structure by Zearalenone (ZEA) in mouse-derived TM4 cells. In order to investigate the role of autophagy, oxidative stress and endoplasmic reticulum(ER) stress in the process of destruction of cytoskeletal structure, the effects of ZEA on the cell viability, cytoskeletal structure, autophagy, oxidative stress, ER stress, MAPK and PI3K- AKT- mTOR signaling pathways were studied. The data demonstrated that ZEA damaged the cytoskeletal structure through the induction of autophagy that leads to the alteration of cytoskeletal structure via elevated oxidative stress. Our results further showed that the autophagy was stimulated by ZEA through PI3K-AKT-mTOR and MAPK signaling pathways in TM4 cells. In addition, ZEA also induced the ER stress which was involved in the induction of the autophagy through inhibiting the ERK signal pathway to suppress the phosphorylation of mTOR. ER stress was involved in the damage of cytoskeletal structure through induction of autophagy by producing ROS. Taken together, this study revealed that ZEA altered the cytoskeletal structure via oxidative stress - autophagy- ER stress pathway in mouse TM4 Sertoli cells.

Polybrominated diphenyl ethers affect the reproduction and development, and alter the sex ratio of zebrafish (Danio rerio)

International Nuclear Information System (INIS)

Han, X.B.; Yuen, Karen W.Y.; Wu, Rudolf S.S.

2013-01-01

Polybrominated diphenyl ethers (PBDEs) have been commonly used as flame retardants and now become ubiquitous in the global environment. Using zebrafish as a model, we tested the hypothesis that PBDEs may affect the reproduction and development of fish. Zebrafish were exposed to environmentally relevant concentrations of DE-71 (a congener of PBDE commonly found in the environment) throughout their whole life cycle, and the effects of DE-71 on gonadal development, gamete quality, fertilization success, hatching success, embryonic development and sex ratio were investigated. Despite gonadal development was enhanced, reductions in spawning, fertilization success, hatching success and larval survival rate were evident, while significant increases in malformation and percentage of male were also observed in the F1 generation. Our laboratory results suggest that PBDEs may pose a risk to reproductive success and alter the sex ratio of fish in environments highly contaminated with PBDEs. -- Highlights: •Zebrafish were exposed to PBDE from eggs to adults. •An increase in Gonadal-Somatic Index and enhanced gonadal development was enhanced. •Fertilization and hatching successes were reduced, while malformation was increased. •PBDE alters sex differentiation, leading to a male biased F1 population. •Environmental relevant concentrations of PBDE threaten natural fish populations. -- PBDE reduces fertilization and hatching successes, causes malformation and leads to a male biased F1 generation in fish

TiO2 nanoparticles disrupt cell adhesion and the architecture of cytoskeletal networks of human osteoblast-like cells in a size dependent manner.

Science.gov (United States)

Ibrahim, Mohamed; Schoelermann, Julia; Mustafa, Kamal; Cimpan, Mihaela R

2018-04-30

Human exposure to titanium dioxide nanoparticles (nano-TiO 2 ) is increasing. An internal source of nano-TiO 2 is represented by titanium-based orthopedic and dental implants can release nanoparticles (NPs) upon abrasion. Little is known about how the size of NPs influences their interaction with cytoskeletal protein networks and the functional/homeostatic consequences that might follow at the implant-bone interface with regard to osteoblasts. We investigated the effects of size of anatase nano-TiO 2 on SaOS-2 human osteoblast-like cells exposed to clinically relevant concentrations (0.05, 0.5, 5 mg/L) of 5 and 40 nm spherical nano-TiO 2 . Cell viability and proliferation, adhesion, spread and migration were assessed, as well as the orientation of actin and microtubule cytoskeletal networks. The phosphorylation of focal adhesion kinase (p-FAK Y397 ) and the expression of vinculin in response to nano-TiO 2 were also assessed. Treatment with nano-TiO 2 disrupted the actin and microtubule cytoskeletal networks leading to morphological modifications of SaOS-2 cells. The phosphorylation of p-FAK Y397 and the expression of vinculin were also modified depending on the particle size, which affected cell adhesion. Consequently, the cell migration was significantly impaired in the 5 nm-exposed cells compared to unexposed cells. The present work shows that the orientation of cytoskeletal networks and the focal adhesion proteins and subsequently the adhesion, spread and migration of SaOS-2 cells were affected by the selected nano-TiO 2 in a size dependent manner. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

A Sustainable Alternative to a Breast Milk Monitoring Program: Using NHANES Serum Data to Estimate Breast Milk PBDE Concentrations

Science.gov (United States)

Polybrominated diphenyl ethers (PBDEs) are high-production-volume chemicals that have been widely used as flame retardants in a variety of consumer products. PBDE concentrations in the environment, wildlife, and humans have been increasing for several decades. Concentrations in t...

Experimental exposure of eggs to polybrominated diphenyl ethers BDE-47 and BDE-99 in red-eared sliders (Trachemys scripta elegans) and snapping turtles (Chelydra serpentina) and possible species-specific differences in debromination.

Science.gov (United States)

Eisenreich, Karen M; Rowe, Christopher L

2013-02-01

Polybrominated diphenyl ethers (PBDEs) are a bioaccumulative, persistent, and toxic class of flame retardants that can potentially impact turtles in natural habitats via exposure through maternal transfer. To simulate maternal transfer in the present study, PBDE congeners BDE-47 and BDE-99 were topically applied to the eggshell and were allowed to diffuse into the egg contents of the red-eared slider (Trachemys scripta elegans) and snapping turtle (Chelydra serpentina). Eggs were topically dosed over 8 d to achieve a target concentration of 40 ng/g in the egg contents. Transfer efficiency was higher for BDE-47 than for BDE-99 in the red-eared sliders (25.8 ± 1.9% vs 9.9 ± 1.1%) and snapping turtles (31.3 ± 1.6% vs 12.5 ± 1.4%), resulting in greater BDE-47 and lower BDE-99 egg content concentrations relative to the 40 ng/g target. However, only 25.8 and 31.3% of the total BDE-47 and 9.9 and 12.5% of the total BDE-99 dose applied could be accounted for in the red-eared slider and snapping turtle egg contents, respectively. Additionally, increased BDE-47 in red-eared slider egg contents dosed with only BDE-99 indicate that BDE-99 might have been debrominated to BDE-47. The efficacy of topical dosing for administering desired embryonic exposures is clearly affected by the chemical properties of the applied compounds and was more successful for BDE-47 in both species. Copyright © 2012 SETAC.

Differential Modulation of Transcription Factors and Cytoskeletal Proteins in Prostate Carcinoma Cells by a Bacterial Lactone

Directory of Open Access Journals (Sweden)

Senthil R. Kumar

2018-01-01

Full Text Available The present study tested the effect of a bacterial lactone N-(3-oxododecanoyl-homoserine lactone (C12-HSL on the cytoskeletal and transcriptional genes and proteins in prostate adenocarcinoma (PA cells (DU145 and LNCaP and prostate small cell neuroendocrine carcinoma (SCNC PC3 cells including their cellular viability and apoptosis. Our data indicate that cell migration and colony formation were affected in the presence of C12-HSL. C12-HSL induced apoptosis and altered viability of both PA and SCNC cells in a concentration dependent manner as measured by fluorescence and chemiluminescence assays. Compared to PCa cells, noncancerous prostate epithelial cells (RWPE1 were resistant to modification by C12-HSL. Further, the viability of PC3 cells in 3D matrix was suppressed by C12-HSL treatment as detected using calcein AM fluorescence in situ. C12-HSL treatment induced cytoskeletal associated protein expression of vinculin and RhoC, which may have implications in cancer cell motility, adhesion, and metastasis. IQGAP protein expression was reduced in DU145 and RWPE1 cells in the presence of C12-HSL. C12-HSL decreased STAT3 phosphorylation in DU145 cells but increased STAT1 protein phosphorylation in PC3 and LNCaP cells. Overall, these studies indicate that C12-HSL can trigger changes in transcription factors and cytoskeletal proteins and thereby modulate growth and migration properties of PCa cells.

Cell elasticity with altered cytoskeletal architectures across multiple cell types.

Science.gov (United States)

Grady, Martha E; Composto, Russell J; Eckmann, David M

2016-08-01

The cytoskeleton is primarily responsible for providing structural support, localization and transport of organelles, and intracellular trafficking. The structural support is supplied by actin filaments, microtubules, and intermediate filaments, which contribute to overall cell elasticity to varying degrees. We evaluate cell elasticity in five different cell types with drug-induced cytoskeletal derangements to probe how actin filaments and microtubules contribute to cell elasticity and whether it is conserved across cell type. Specifically, we measure elastic stiffness in primary chondrocytes, fibroblasts, endothelial cells (HUVEC), hepatocellular carcinoma cells (HUH-7), and fibrosarcoma cells (HT 1080) subjected to two cytoskeletal destabilizers: cytochalasin D and nocodazole, which disrupt actin and microtubule polymerization, respectively. Elastic stiffness is measured by atomic force microscopy (AFM) and the disruption of the cytoskeleton is confirmed using fluorescence microscopy. The two cancer cell lines showed significantly reduced elastic moduli values (~0.5kPa) when compared to the three healthy cell lines (~2kPa). Non-cancer cells whose actin filaments were disrupted using cytochalasin D showed a decrease of 60-80% in moduli values compared to untreated cells of the same origin, whereas the nocodazole-treated cells showed no change in elasticity. Overall, we demonstrate actin filaments contribute more to elastic stiffness than microtubules but this result is cell type dependent. Cancer cells behaved differently, exhibiting increased stiffness as well as stiffness variability when subjected to nocodazole. We show that disruption of microtubule dynamics affects cancer cell elasticity, suggesting therapeutic drugs targeting microtubules be monitored for significant elastic changes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of the neuronal apoptotic pathways involved in cytoskeletal disruption-induced apoptosis.

Science.gov (United States)

Jordà, Elvira G; Verdaguer, Ester; Jimenez, Andrés; Arriba, S Garcia de; Allgaier, Clemens; Pallàs, Mercè; Camins, Antoni

2005-08-01

The cytoskeleton is critical to neuronal functioning and survival. Cytoskeletal alterations are involved in several neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. We studied the possible pathways involved in colchicine-induced apoptosis in cerebellar granule neurons (CGNs). Although colchicine evoked an increase in caspase-3, caspase-6 and caspase-9 activation, selective caspase inhibitors did not attenuate apoptosis. Inhibitors of other cysteine proteases such as PD150606 (a calpain-specific inhibitor), Z-Phe-Ala fluoromethyl ketone (a cathepsins-inhibitors) and N(alpha)-p-tosyl-l-lysine chloromethyl ketone (serine-proteases inhibitor) also had no effect on cell death/apoptosis induced by colchicine. However, BAPTA-AM 10 microM (intracellular calcium chelator) prevented apoptosis mediated by cytoskeletal alteration. These data indicate that calcium modulates colchicine-induced apoptosis in CGNs. PARP-1 inhibitors did not prevent apoptosis mediated by colchicine. Finally, colchicine-induced apoptosis in CGNs was attenuated by kenpaullone, a cdk5 inhibitor. Kenpaullone and indirubin also prevented cdk5/p25 activation mediated by colchicine. These findings indicate that cytoskeletal alteration can compromise cdk5 activation, regulating p25 formation and suggest that cdk5 inhibitors attenuate apoptosis mediated by cytoskeletal alteration. The present data indicate the potential therapeutic value of drugs that prevent the formation of p25 for the treatment of neurodegenerative disorders.

Cytoskeletal Tropomyosin Tm5NM1 Is Required for Normal Excitation–Contraction Coupling in Skeletal Muscle

OpenAIRE

Vlahovich, Nicole; Kee, Anthony J.; Van der Poel, Chris; Kettle, Emma; Hernandez-Deviez, Delia; Lucas, Christine; Lynch, Gordon S.; Parton, Robert G.; Gunning, Peter W.; Hardeman, Edna C.

2009-01-01

The functional diversity of the actin microfilaments relies in part on the actin binding protein tropomyosin (Tm). The muscle-specific Tms regulate actin-myosin interactions and hence contraction. However, there is less known about the roles of the numerous cytoskeletal isoforms. We have shown previously that a cytoskeletal Tm, Tm5NM1, defines a Z-line adjacent cytoskeleton in skeletal muscle. Recently, we identified a second cytoskeletal Tm in this region, Tm4. Here we show that Tm4 and Tm5N...

Effect of developmental low dose PBDE 47 exposure on thyroid hormone status and serum concentrations of FSH and inhibin B in male rats

Energy Technology Data Exchange (ETDEWEB)

Andrade, A.J.M.; Kuriyama, S.N.; Akkoc, Z.; Talsness, C.E.; Chahoud, I. [Charite Univ. Medical School Berlin (Germany). Inst. of Clinical Pharmacology and Toxicology, Dept. Toxicology, Campus Benjamin Franklin

2004-09-15

Several persistent halogenated organic compounds such as PCBs, dioxins and more recently, polybrominated diphenyl ethers (PBDEs) have been shown to disrupt thyroid hormone homeostasis in experimental animals. Particular concern exists regarding exposure to these compounds during critical periods of development when thyroid hormones orchestrate the growth and differentiation of many organs including the brain and the testis. While the contamination levels of PCBs and other persistent organic pollutants have declined in the past years, increasing levels of PBDEs have been detected in environmental and human samples including human breast milk. PBDEs are produced in large quantities and used worldwide as flame retardants in electrical appliances, carpets and furniture upholstery. Similar to other halogenated environmental organic pollutants, PBDEs seem to present a wide range of toxic effects including reproductive, endocrine, neurobehavioral and hepatic toxicity. Recently, it has been demonstrated that in utero and pubertal exposures to DE-71 (a commercial mixture containing mostly tetra- and penta-bromodiphenyl ethers) significantly reduce thyroxine levels (T4) in rats. The present study has focused on the possible effects of the tetra- BDE congener 2,2'4,4'-tetrabromo diphenyl ether (PBDE 47) on thyroid hormone status and associated changes on FSH and inhibin B levels in the developing male rat. We administered a single dose to gravid dams on gestation day 6 of either 140 {mu}g/kg BW or 700 {mu}g/kg BW PBDE 47. These doses are pertinent to human exposure situation because a study by She et al.3 found a mean level of 33.3 {mu}g PBDE 47 /kg fat in human breast adipose tissue with a range from 7.01 to 196 {mu}g PBDE 47 /kg fat.

Levels of Polybrominated Diphenyl Ether (PBDE) flame retardants in animals representing different trophic levels of the North Sea food web

NARCIS (Netherlands)

Boon, J.P.; Lewis, W.E.; Tjoen-A-Choy, M.R.; Allchin, C.R.; Law, R.J.; Boer, de J.

2002-01-01

The levels of individual PBDE congeners were investigated in the invertebrate species whelk (Buccinum undatum), seastar (Asterias rubens), and hermit crab (Pagurus bernhardus), the gadoid fish species whiting (Merlangius merlangus) and cod (Gadus morhua), and the marine mammal species harbor seal

Age and seasonal variability of polybrominated diphenyl ethers in free-ranging East Greenland polar bears (Ursus maritimus)

International Nuclear Information System (INIS)

Dietz, Rune; Riget, Frank F.; Sonne, Christian; Letcher, Robert J.; Backus, Sean; Born, Erik W.; Kirkegaard, Maja; Muir, Derek C.G.

2007-01-01

Polybrominated diphenyl ethers (PBDEs) were analysed in adipose tissue from 92 East Greenland polar bears (Ursus maritimus) sampled during 1999-2001. Mean ΣPBDE concentrations were 70 ng/g lipid weight (lw) (range: 22-192 ng/g lw) and showed no relationship with age or sex. Of the 32 analysed PBDE congeners; BDE47, BDE153, BDE99 and BDE100 dominated, and comprised 99.6% of the ΣPBDE concentration. The ΣPBDE concentration had a highly significant correlation with ΣPCB, ΣCHL, dieldrin, HCB and ΣHCH concentrations. We found a seasonal pattern of median ΣPBDE concentration with 1.2 to 1.8 times higher concentrations in March to July than the rest of the year. The seasonal variation also provides a clue to the seasonal exposure, bio-availability, toxic exposure and degradation. We suggest that future geographical PBDE data comparisons may not need corrections for sex or age, but such data sets should be corrected for seasonal variability, using the presented correctional trigonometric regression. - Mean ΣPBDE concentrations of East Greenland polar bears (Ursus maritimus) were 69.5 ng/g lw (range: 21.7-192 ng/g lw) and showed a seasonal pattern with no relationship with age and sex

Detection of cytoskeletal proteins in small cell lung carcinoma

Czech Academy of Sciences Publication Activity Database

Hložánková, M.; Lukáš, Z.; Viklický, Vladimír

1999-01-01

Roč. 18, - (1999), s. 47-49 ISSN 0231-5882 Grant - others:MŠk1(CZ) OE10a/EU1450 Keywords : cytoskeletal proteins * small cell lung carcinoma Subject RIV: EI - Biotechnology ; Bionics Impact factor: 0.400, year: 1999

Levels of polybrominated diphenyl ether (PBDE) flame retardants in animals representing different trophic levels of the North Sea food Web.

Science.gov (United States)

Boon, Jan P; Lewis, Wilma E; Tjoen-A-Choy, Michael R; Allchin, Colin R; Law, Robin J; De Boer, Jacob; Ten Hallers-Tjabbes, Cato C; Zegers, Bart N

2002-10-01

The levels of individual PBDE congeners were investigated in the invertebrate species whelk (Buccinum undatum), seastar (Asterias rubens), and hermit crab (Pagurus bernhardus), the gadoid fish species whiting (Merlangius merlangus) and cod (Gadus morhua), and the marine mammal species harbor seal (Phoca vitulina) and harbor porpoise (Phocoena phocoena). These species are all important representatives of different trophic levels of the North Sea food web. All six major PBDE congeners detected (BDEs 28, 47, 99, 100, 153, and 154) are most prevalent in the commercial Penta-BDE formulation. There is no evidence for the occurrence of the Octa-BDE formulation in the North Sea food web, since its dominant congener, BDE183, was never detected. BDE209, the main congener (> 97%) in the Deca-BDE formulation, was detected only in a minority of the samples and always in concentrations around the limit of detection. Since BDE209 is often the major BDE congener in sediments from the area, the main reason for its low concentrations in biota from the North Sea seems to be a relatively low bioaccumulation potential. This can either be due to a low uptake rate of the very large molecule or a relatively rapid excretion after biotransformation. Since all invertebrates investigated are sentinel species, they are highly representative for the area of capture. The highest lipid-normalized concentrations of PBDEs in the invertebrates occurred near the mouth of the river Tees at the East coast of the UK. The geographical distribution of the PBDEs can be explained by the residual currents in the area. The direction of these currents differs between the summer and the winter season as a result of the presence or absence of vertical summer stratification of the deeper waters north of the Dogger Bank. Summer stratification results in the development of a density-driven bottom water current formed after the onset of vertical stratification of the water column in May leaving the UK coast near

Effect of polybrominated diphenyl ether (PBDE) treatment on the composition and function of the bacterial community in the sponge Haliclona cymaeformis.

KAUST Repository

Tian, Ren-Mao; Lee, On On; Wang, Yong; Cai, Lin; Bougouffa, Salim; Chiu, Jill Man Ying; Wu, Rudolf Shiu Sun; Qian, Pei-Yuan

2014-01-01

. In the present study, we studied the short-period effect of PBDE-47 (2,2',4,4'-tetrabromodiphenyl ether) treatment on the community structure and functional gene composition of the bacterial community inhabiting the marine sponge Haliclona cymaeformis. Our

A Sustainable Alternative to a U.S. Breast Milk Monitoring Program: Using NHANES Serum Data to Estimate Breast Milk PBDE Concentrations

Science.gov (United States)

Polybrominated diphenyl ethers (PBDEs) are high-production-volume chemicals that have been widely used as flame retardants in a variety of consumer products. PBDE concentrations in the environment, wildlife, and humans have been increasing for several decades. Concentrations in t...

Dendritic Cytoskeletal Architecture Is Modulated by Combinatorial Transcriptional Regulation in Drosophila melanogaster.

Science.gov (United States)

Das, Ravi; Bhattacharjee, Shatabdi; Patel, Atit A; Harris, Jenna M; Bhattacharya, Surajit; Letcher, Jamin M; Clark, Sarah G; Nanda, Sumit; Iyer, Eswar Prasad R; Ascoli, Giorgio A; Cox, Daniel N

2017-12-01

Transcription factors (TFs) have emerged as essential cell autonomous mediators of subtype specific dendritogenesis; however, the downstream effectors of these TFs remain largely unknown, as are the cellular events that TFs control to direct morphological change. As dendritic morphology is largely dictated by the organization of the actin and microtubule (MT) cytoskeletons, elucidating TF-mediated cytoskeletal regulatory programs is key to understanding molecular control of diverse dendritic morphologies. Previous studies in Drosophila melanogaster have demonstrated that the conserved TFs Cut and Knot exert combinatorial control over aspects of dendritic cytoskeleton development, promoting actin and MT-based arbor morphology, respectively. To investigate transcriptional targets of Cut and/or Knot regulation, we conducted systematic neurogenomic studies, coupled with in vivo genetic screens utilizing multi-fluor cytoskeletal and membrane marker reporters. These analyses identified a host of putative Cut and/or Knot effector molecules, and a subset of these putative TF targets converge on modulating dendritic cytoskeletal architecture, which are grouped into three major phenotypic categories, based upon neuromorphometric analyses: complexity enhancer, complexity shifter, and complexity suppressor. Complexity enhancer genes normally function to promote higher order dendritic growth and branching with variable effects on MT stabilization and F-actin organization, whereas complexity shifter and complexity suppressor genes normally function in regulating proximal-distal branching distribution or in restricting higher order branching complexity, respectively, with spatially restricted impacts on the dendritic cytoskeleton. Collectively, we implicate novel genes and cellular programs by which TFs distinctly and combinatorially govern dendritogenesis via cytoskeletal modulation. Copyright © 2017 by the Genetics Society of America.

Ultrafine particles cause cytoskeletal dysfunctions in macrophages: role of intracellular calcium

Directory of Open Access Journals (Sweden)

Brown David M

2005-10-01

Full Text Available Abstract Background Particulate air pollution is reported to cause adverse health effects in susceptible individuals. Since most of these particles are derived form combustion processes, the primary composition product is carbon with a very small diameter (ultrafine, less than 100 nm in diameter. Besides the induction of reactive oxygen species and inflammation, ultrafine particles (UFP can cause intracellular calcium transients and suppression of defense mechanisms of alveolar macrophages, such as impaired migration or phagocytosis. Methods In this study the role of intracellular calcium transients caused by UFP was studied on cytoskeleton related functions in J774A.1 macrophages. Different types of fine and ultrafine carbon black particles (CB and ufCB, respectively, such as elemental carbon (EC90, commercial carbon (Printex 90, diesel particulate matter (DEP and urban dust (UD, were investigated. Phagosome transport mechanisms and mechanical cytoskeletal integrity were studied by cytomagnetometry and cell viability was studied by fluorescence microscopy. Macrophages were exposed in vitro with 100 and 320 μg UFP/ml/million cells for 4 hours in serum free medium. Calcium antagonists Verapamil, BAPTA-AM and W-7 were used to block calcium channels in the membrane, to chelate intracellular calcium or to inhibit the calmodulin signaling pathways, respectively. Results Impaired phagosome transport and increased cytoskeletal stiffness occurred at EC90 and P90 concentrations of 100 μg/ml/million cells and above, but not with DEP or UD. Verapamil and W-7, but not BAPTA-AM inhibited the cytoskeletal dysfunctions caused by EC90 or P90. Additionally the presence of 5% serum or 1% bovine serum albumin (BSA suppressed the cytoskeletal dysfunctions. Cell viability showed similar results, where co-culture of ufCB together with Verapamil, W-7, FCS or BSA produced less cell dead compared to the particles only.

Environmental pollution of polybrominated diphenyl ethers from industrial plants in China: a preliminary investigation.

Science.gov (United States)

Deng, Chao; Chen, Yuan; Li, Jinhui; Li, Ying; Li, Huafen

2016-04-01

Although numerous studies have shown the presence of polybrominated diphenyl ethers (PBDEs) in various environmental media, attention to their distribution in the environmental media surrounding industrial facilities is limited. In this study, eight PBDEs congeners (BDE-28, -47, -99, -100, -153, -154, -183, -209) were investigated in surface soils and water samples collected from commercial PBDE manufacturers, flame-retardant plastic modification plants and waste electrical and electronic equipment recycling facilities in China. Analysis of target compounds was performed using the model NCI GC-MS in SIM mode. The concentrations of ∑8PBDEs varied from 193.1 to 22,004.3 ng/L in water samples and from 1209.3 to 226,906 ng/g dry wt in surface soils, respectively. More severe PBDE contamination, when compared with previously reported data, was found in industrial areas in this study. This indicates that these industrial areas are highly polluted with PBDEs. BDE-209 was the predominant congener, accounting for more than 94% in this study, except for a 68.75% portion at one site. Our results show that PBDE manufacturing and flame-retardant plastic modification plants, easily overlooked by the public, are two primary PBDE pollution sources although they affect surrounding areas. Further research is needed, aimed at managing industrial PBDE emissions and eliminating environmental PBDE pollution, to investigate the material flows and environmental fates of PBDEs in all stages of the life cycle.

Visualization of cytoskeletal elements by the atomic force microscope

International Nuclear Information System (INIS)

Berdyyeva, T.; Woodworth, C.D.; Sokolov, I.

2005-01-01

We describe a novel application of atomic force microscopy (AFM) to directly visualize cytoskeletal fibers in human foreskin epithelial cells. The nonionic detergent Triton X-100 in a low concentration was used to remove the membrane, soluble proteins, and organelles from the cell. The remaining cytoskeleton can then be directly visualized in either liquid or air-dried ambient conditions. These two types of scanning provide complimentary information. Scanning in liquid visualizes the surface filaments of the cytoskeleton, whereas scanning in air shows both the surface filaments and the total 'volume' of the cytoskeletal fibers. The smallest fibers observed were ca. 50 nm in diameter. The lateral resolution of this technique was ca.20 nm, which can be increased to a single nanometer level by choosing sharper AFM tips. Because the AFM is a true 3D technique, we are able to quantify the observed cytoskeleton by its density and volume. The types of fibers can be identified by their size, similar to electron microscopy

Polybrominated Diphenyl Ethers in Human Milk and Serum from the U.S. EPA MAMA Study: Modeled Predictions of Infant Exposure and Considerations for Risk Assessment

Science.gov (United States)

Marchitti, Satori A.; Fenton, Suzanne E.; Mendola, Pauline; Kenneke, John F.; Hines, Erin P.

2016-01-01

Background: Serum concentrations of polybrominated diphenyl ethers (PBDEs) in U.S. women are believed to be among the world’s highest; however, little information exists on the partitioning of PBDEs between serum and breast milk and how this may affect infant exposure. Objectives: Paired milk and serum samples were measured for PBDE concentrations in 34 women who participated in the U.S. EPA MAMA Study. Computational models for predicting milk PBDE concentrations from serum were evaluated. Methods: Samples were analyzed using gas chromatography isotope-dilution high-resolution mass spectrometry. Observed milk PBDE concentrations were compared with model predictions, and models were applied to NHANES serum data to predict milk PBDE concentrations and infant intakes for the U.S. population. Results: Serum and milk samples had detectable concentrations of most PBDEs. BDE-47 was found in the highest concentrations (median serum: 18.6; milk: 31.5 ng/g lipid) and BDE-28 had the highest milk:serum partitioning ratio (2.1 ± 0.2). No evidence of depuration was found. Models demonstrated high reliability and, as of 2007–2008, predicted U.S. milk concentrations of BDE-47, BDE-99, and BDE-100 appear to be declining but BDE-153 may be rising. Predicted infant intakes (ng/kg/day) were below threshold reference doses (RfDs) for BDE-99 and BDE-153 but above the suggested RfD for BDE-47. Conclusions: Concentrations and partitioning ratios of PBDEs in milk and serum from women in the U.S. EPA MAMA Study are presented for the first time; modeled predictions of milk PBDE concentrations using serum concentrations appear to be a valid method for estimating PBDE exposure in U.S. infants. Citation: Marchitti SA, Fenton SE, Mendola P, Kenneke JF, Hines EP. 2017. Polybrominated diphenyl ethers in human milk and serum from the U.S. EPA MAMA Study: modeled predictions of infant exposure and considerations for risk assessment. Environ Health Perspect 125:706–713; http://dx.doi.org/10

Prey species as possible sources of PBDE exposures for peregrine falcons (Falco peregrinus) nesting in major California cities.

Science.gov (United States)

Park, June-Soo; Fong, Alison; Chu, Vivian; Holden, Arthur; Linthicum, Janet; Hooper, Kim

2011-04-01

Our earlier findings indicate that (1) peregrine falcons (Falco peregrinus anatum Bonaparte) nesting in major California cities have among the highest polybrominated diphenyl ether (PBDE) levels in the world (max ∑PBDEs=100 ppm), and (2) Big City peregrines have higher levels and proportions of the higher-brominated congeners (hepta- to deca-BDEs) than do their Coastal counterparts. In this study we classified the prey species (n =185) from the remains of prey (feathers) at 38 peregrine nest sites over 25 years (1974-1998). We grouped the prey species into 15 categories based on diet and found distinctly different prey patterns for Big City vs. Coastal peregrines. Big City peregrines had a higher (almost three times) weight percentage intake of food waste-eating birds (e.g., rock pigeons, Columba livia) than Coastal peregrines. These differing prey patterns suggest diet as a potential source of the unusually high levels and proportions of higher-brominated PBDEs in Big City peregrines. The relative contributions of diet and dust (e.g., preening) exposure to PBDE patterns in Big City peregrines will be explored in future investigations. © Springer Science+Business Media, LLC 2010

Effect of polybrominated diphenyl ether congeners on placental cytokine production.

Science.gov (United States)

Arita, Yuko; Yeh, Corinne; Thoma, Theodosia; Getahun, Darios; Menon, Ramkumar; Peltier, Morgan R

2018-02-01

Polybrominated diphenyl ethers (PBDEs) are pollutants that may increase the risk of preterm birth. In previous studies, we found that a mixture of PBDEs altered the expression of biomarkers for preterm birth by the placenta. However, there are 209 different PBDE congeners with different tissue distributions. How these different congeners may alter the production of immunomodulators by the placenta that help to maintain the survival of the fetal allograft is unclear. Therefore, we compared the effects 5 common congeners on basal and bacteria-stimulated cytokine production by the placenta. Placental explant cultures were incubated with 20 μM of PBDE congeners 47, 99, 100, 153, 209 or vehicle in the presence and absence of Escherichia coli for 20 h. Conditioned medium was harvested and concentrations of IL-1β, TNF-α, IL-6, sgp130, HO-1, IL-10, BDNF, and 8-IsoP quantified. For unstimulated cultures, all congeners, except for PBDE-47, reduced the production of IL-1β and IL-6 production was enhanced by PBDE-153. BDNF concentrations tended to be reduced by most PBDE congeners and IL-10 production was enhanced by PBDE-99, -153, and -209. 8-IsoP production was enhanced by PBDE-153, but not the other congeners. For bacteria-stimulated cultures, PBDE-47 increased IL-1β production and PBDE-47, -153, and -209 tended to reduce TNF-α production. IL-6 production was enhanced by all PBDEs except 153. IL-10 production was enhanced by all congeners except for PBDE-47. All congeners significantly enhanced BDNF and 8-IsoP. These results suggest that PBDEs can alter the expression of placental biomarkers in a congener and infection-dependent manner. Copyright © 2018 Elsevier B.V. All rights reserved.

Cytoskeletal Components Define Protein Location to Membrane Microdomains*

Science.gov (United States)

Szymanski, Witold G.; Zauber, Henrik; Erban, Alexander; Gorka, Michal; Wu, Xu Na; Schulze, Waltraud X.

2015-01-01

The plasma membrane is an important compartment that undergoes dynamic changes in composition upon external or internal stimuli. The dynamic subcompartmentation of proteins in ordered low-density (DRM) and disordered high-density (DSM) membrane phases is hypothesized to require interactions with cytoskeletal components. Here, we systematically analyzed the effects of actin or tubulin disruption on the distribution of proteins between membrane density phases. We used a proteomic screen to identify candidate proteins with altered submembrane location, followed by biochemical or cell biological characterization in Arabidopsis thaliana. We found that several proteins, such as plasma membrane ATPases, receptor kinases, or remorins resulted in a differential distribution between membrane density phases upon cytoskeletal disruption. Moreover, in most cases, contrasting effects were observed: Disruption of actin filaments largely led to a redistribution of proteins from DRM to DSM membrane fractions while disruption of tubulins resulted in general depletion of proteins from the membranes. We conclude that actin filaments are necessary for dynamic movement of proteins between different membrane phases and that microtubules are not necessarily important for formation of microdomains as such, but rather they may control the protein amount present in the membrane phases. PMID:26091700

Cytoskeletal Regulation Dominates Temperature-Sensitive Proteomic Changes of Hibernation in Forebrain of 13-Lined Ground Squirrels

Science.gov (United States)

Hindle, Allyson G.; Martin, Sandra L.

2013-01-01

13-lined ground squirrels, Ictidomys tridecemlineatus, are obligate hibernators that transition annually between summer homeothermy and winter heterothermy – wherein they exploit episodic torpor bouts. Despite cerebral ischemia during torpor and rapid reperfusion during arousal, hibernator brains resist damage and the animals emerge neurologically intact each spring. We hypothesized that protein changes in the brain underlie winter neuroprotection. To identify candidate proteins, we applied a sensitive 2D gel electrophoresis method to quantify protein differences among forebrain extracts prepared from ground squirrels in two summer, four winter and fall transition states. Proteins that differed among groups were identified using LC-MS/MS. Only 84 protein spots varied significantly among the defined states of hibernation. Protein changes in the forebrain proteome fell largely into two reciprocal patterns with a strong body temperature dependence. The importance of body temperature was tested in animals from the fall; these fall animals use torpor sporadically with body temperatures mirroring ambient temperatures between 4 and 21°C as they navigate the transition between summer homeothermy and winter heterothermy. Unlike cold-torpid fall ground squirrels, warm-torpid individuals strongly resembled the homeotherms, indicating that the changes observed in torpid hibernators are defined by body temperature, not torpor per se. Metabolic enzymes were largely unchanged despite varied metabolic activity across annual and torpor-arousal cycles. Instead, the majority of the observed changes were cytoskeletal proteins and their regulators. While cytoskeletal structural proteins tended to differ seasonally, i.e., between summer homeothermy and winter heterothermy, their regulatory proteins were more strongly affected by body temperature. Changes in the abundance of various isoforms of the microtubule assembly and disassembly regulatory proteins dihydropyrimidinase

Cytoskeletal regulation dominates temperature-sensitive proteomic changes of hibernation in forebrain of 13-lined ground squirrels.

Directory of Open Access Journals (Sweden)

Allyson G Hindle

Full Text Available 13-lined ground squirrels, Ictidomys tridecemlineatus, are obligate hibernators that transition annually between summer homeothermy and winter heterothermy - wherein they exploit episodic torpor bouts. Despite cerebral ischemia during torpor and rapid reperfusion during arousal, hibernator brains resist damage and the animals emerge neurologically intact each spring. We hypothesized that protein changes in the brain underlie winter neuroprotection. To identify candidate proteins, we applied a sensitive 2D gel electrophoresis method to quantify protein differences among forebrain extracts prepared from ground squirrels in two summer, four winter and fall transition states. Proteins that differed among groups were identified using LC-MS/MS. Only 84 protein spots varied significantly among the defined states of hibernation. Protein changes in the forebrain proteome fell largely into two reciprocal patterns with a strong body temperature dependence. The importance of body temperature was tested in animals from the fall; these fall animals use torpor sporadically with body temperatures mirroring ambient temperatures between 4 and 21°C as they navigate the transition between summer homeothermy and winter heterothermy. Unlike cold-torpid fall ground squirrels, warm-torpid individuals strongly resembled the homeotherms, indicating that the changes observed in torpid hibernators are defined by body temperature, not torpor per se. Metabolic enzymes were largely unchanged despite varied metabolic activity across annual and torpor-arousal cycles. Instead, the majority of the observed changes were cytoskeletal proteins and their regulators. While cytoskeletal structural proteins tended to differ seasonally, i.e., between summer homeothermy and winter heterothermy, their regulatory proteins were more strongly affected by body temperature. Changes in the abundance of various isoforms of the microtubule assembly and disassembly regulatory proteins

Antibodies to cytoskeletal proteins as evidenced by immunofluorescence microscopy and radioimmunoassay

International Nuclear Information System (INIS)

Zugehoer, M.; Struy, H.; Morenz, J.

1987-01-01

In patients suffering from chronic hepatitis, collagenosis and infectious mononucleosis, resp., as well as in blood donors antibodies against cytoskeletal antigens such as actin, myosin, actinin, desmin, keratin, and tubulin were determined by radioimmunoassay

Antibodies to cytoskeletal proteins as evidenced by immunofluorescence microscopy and radioimmunoassay

Energy Technology Data Exchange (ETDEWEB)

Zugehoer, M; Struy, H; Morenz, J

1987-01-01

In patients suffering from chronic hepatitis, collagenosis and infectious mononucleosis, resp., as well as in blood donors antibodies against cytoskeletal antigens such as actin, myosin, actinin, desmin, keratin, and tubulin were determined by radioimmunoassay.

Diversity of Histologic Patterns and Expression of Cytoskeletal Proteins in Canine Skeletal Osteosarcoma.

Science.gov (United States)

Nagamine, E; Hirayama, K; Matsuda, K; Okamoto, M; Ohmachi, T; Kadosawa, T; Taniyama, H

2015-09-01

Osteosarcoma (OS), the most common bone tumor, includes OS of the head (OSH) and appendicular OS (OSA). In dogs, it is classified into 6 histologic subtypes: osteoblastic, chondroblastic, fibroblastic, telangiectatic, giant cell, and poorly differentiated. This study investigated the significance of the histologic classification relevant to clinical outcome and the histologic and immunohistochemical relationships between pleomorphism and expression of cytoskeletal proteins in 60 cases each of OSH and OSA. Most neoplasms exhibited histologic diversity, and 64% of OS contained multiple subtypes. In addition to the above 6 subtypes, myxoid, round cell, and epithelioid subtypes were observed. Although the epithelioid subtypes were observed in only OSH, no significant difference in the frequency of other subtypes was observed. Also, no significant relevance was observed between the clinical outcome and histologic subtypes. Cytokeratin (CK) was expressed in both epithelioid and sarcomatoid tumor cells in various subtypes, and all CK-positive tumor cells also expressed vimentin. Vimentin and α-smooth muscle actin (SMA) were expressed in all subtypes. A few SMA-positive spindle-shaped tumor cells exhibited desmin expression. Glial fibrillary acidic protein-positive tumor cells were observed in many subtypes, and some of these cells showed neurofilament expression. Although OSH exhibited significantly stronger immunoreactivity for SMA than OSA, no significant difference in other cytoskeletal proteins was observed. Some tumor cells had cytoskeletal protein expression compatible with the corresponding histologic subtypes, such as CK in the epithelioid subtype and SMA in the fibroblastic subtype. Thus, canine skeletal OS is composed of pleomorphic and heterogenous tumor cells as is reflected in the diversity of histologic patterns and expression of cytoskeletal proteins. © The Author(s) 2015.

SEPTIN2 and STATHMIN Regulate CD99-Mediated Cellular Differentiation in Hodgkin's Lymphoma.

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Wenjing Jian

Full Text Available Hodgkin's lymphoma (HL is a lymphoid neoplasm characterized by Hodgkin's and Reed-Sternberg (H/RS cells, which is regulated by CD99. We previously reported that CD99 downregulation led to the transformation of murine B lymphoma cells (A20 into cells with an H/RS phenotype, while CD99 upregulation induced differentiation of classical Hodgkin's lymphoma (cHL cells (L428 into terminal B-cells. However, the molecular mechanism remains unclear. In this study, using fluorescence two-dimensional differential in-gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS, we have analyzed the alteration of protein expression following CD99 upregulation in L428 cells as well as downregulation of mouse CD99 antigen-like 2 (mCD99L2 in A20 cells. Bioinformatics analysis showed that SEPTIN2 and STATHMIN, which are cytoskeleton proteins, were significantly differentially expressed, and chosen for further validation and functional analysis. Differential expression of SEPTIN2 was found in both models and was inversely correlated with CD99 expression. STATHMIN was identified in the A20 cell line model and its expression was positively correlated with that of CD99. Importantly, silencing of SEPTIN2 with siRNA substantially altered the cellular cytoskeleton in L428 cells. The downregulation of STATHMIN by siRNA promoted the differentiation of H/RS cells toward terminal B-cells. These results suggest that SEPTIN2-mediated cytoskeletal rearrangement and STATHMIN-mediated differentiation may contribute to changes in cell morphology and differentiation of H/RS cells with CD99 upregulation in HL.

Acute fluoride poisoning alters myocardial cytoskeletal and AMPK signaling proteins in rats.

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Panneerselvam, Lakshmikanthan; Raghunath, Azhwar; Perumal, Ekambaram

2017-02-15

Our previous findings revealed that increased oxidative stress, apoptosis and necrosis were implicated in acute fluoride (F - ) induced cardiac dysfunction apart from hypocalcemia and hyperkalemia. Cardiac intermediate filaments (desmin and vimentin) and cytoskeleton linker molecule vinculin plays an imperative role in maintaining the architecture of cardiac cytoskeleton. In addition, AMPK is a stress activated kinase that regulates the energy homeostasis during stressed state. The present study was aimed to examine the role of cytoskeletal proteins and AMPK signaling molecules in acute F - induced cardiotoxicity in rats. In order to study this, male Wistar rats were treated with single oral doses of 45 and 90mg/kgF - for 24h. Acute F - intoxicated rats showed declined cytoskeletal protein expression of desmin, vimentin and vinculin in a dose dependent manner compared to control. A significant increase in phosphorylation of AMPKα (Thr172), AMPKß1 (Ser108) and Acetyl-coA carboxylase (ACC) (Ser79) in the myocardium and associated ATP deprivation were found in acute F - intoxicated rats. Further, ultra-structural studies confirmed myofibril lysis with interruption of Z lines, dilated sarcoplasmic reticulum and damaged mitochondrion were observed in both the groups of F - intoxicated rats. Taken together, these findings reveal that acute F - exposure causes sudden heart failure by altering the expression of cytoskeletal proteins and AMPK signaling molecules. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Polybrominated diphenyl ethers enhance the production of proinflammatory cytokines by the placenta.

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Peltier, M R; Klimova, N G; Arita, Y; Gurzenda, E M; Murthy, A; Chawala, K; Lerner, V; Richardson, J; Hanna, N

2012-09-01

Polybrominated diphenyl ether(s) (PBDE) are ubiquitous environmental contaminants that bind and cross the placenta but their effects on pregnancy outcome are unclear. It is possible that environmental contaminants increase the risk of inflammation-mediated pregnancy complications such as preterm birth by promoting a proinflammatory environment at the maternal-fetal interface. We hypothesized that PBDE would reduce IL-10 production and enhance the production of proinflammatory cytokines associated with preterm labor/birth by placental explants. Second-trimester placental explants were cultured in either vehicle (control) or 2 μM PBDE mixture of congers 47, 99 and 100 for 72 h. Cultures were then stimulated with 10(6) CFU/ml heat-killed Escherichia coli for a final 24 h incubation and conditioned medium was harvested for quantification of cytokines and PGE(2). COX-2 content and viability of the treated tissues were then quantified by tissue ELISA and MTT reduction activity, respectively. PBDE pre-treatment reduced E. coli-stimulated IL-10 production and significantly increased E. coli-stimulated IL-1β secretion. PBDE exposure also increased basal and bacteria-stimulated COX-2 expression. Basal, but not bacteria-stimulated PGE(2), was also enhanced by PBDE exposure. No effect of PBDE on viability of the explants cultures was detected. In summary, pre-exposure of placental explants to congers 47, 99, and 100 enhanced the placental proinflammatory response to infection. This may increase the risk of infection-mediated preterm birth by lowering the threshold for bacteria to stimulate a proinflammatory response(s). Copyright © 2012 Elsevier Ltd. All rights reserved.

A novel system of cytoskeletal elements in the human pathogen Helicobacter pylori.

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Barbara Waidner

2009-11-01

Full Text Available Pathogenicity of the human pathogen Helicobacter pylori relies upon its capacity to adapt to a hostile environment and to escape from the host response. Therefore, cell shape, motility, and pH homeostasis of these bacteria are specifically adapted to the gastric mucus. We have found that the helical shape of H. pylori depends on coiled coil rich proteins (Ccrp, which form extended filamentous structures in vitro and in vivo, and are differentially required for the maintenance of cell morphology. We have developed an in vivo localization system for this pathogen. Consistent with a cytoskeleton-like structure, Ccrp proteins localized in a regular punctuate and static pattern within H. pylori cells. Ccrp genes show a high degree of sequence variation, which could be the reason for the morphological diversity between H. pylori strains. In contrast to other bacteria, the actin-like MreB protein is dispensable for viability in H. pylori, and does not affect cell shape, but cell length and chromosome segregation. In addition, mreB mutant cells displayed significantly reduced urease activity, and thus compromise a major pathogenicity factor of H. pylori. Our findings reveal that Ccrp proteins, but not MreB, affect cell morphology, while both cytoskeletal components affect the development of pathogenicity factors and/or cell cycle progression.

Exposure to polybrominated diphenyl ethers (PBDEs): Changes in thyroid, vitamin A, glutathione homeostasis, and oxidative stress in American kestrels (Falco sparverius)

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Fernie, K.J.; Shutt, J.L.; Mayne, G.; Hoffman, D.; Letcher, R.J.; Drouillard, K.G.; Ritchie, I.J.

2005-01-01

Polybrominated diphenyl ethers (PBDEs), a class of additive flame retardants, are temporally increasing in wildlife tissues and capable of disrupting normal endocrine function. We determined whether in ovo and post-hatch exposure of captive American kestrels (Falco sparverius) to environmentally relevant PBDEs alter thyroid, retinol, and oxidative stress measures. Control eggs were injected with safflower oil and subsequent nestlings fed the same vehicle; dosed eggs received PBDE congeners (BDE-47, -99, -100, -153), which mainly comprise the Penta-BDE commercial mixture, dissolved in safflower oil at concentrations (1500 ng/g total [Sigma] PBDEs) approximating those in Great Lakes gull eggs. Nestlings hatching from dosed eggs were orally exposed for 29 days to variable Sigma PBDE concentrations that are similar to levels reported in tissues of Great Lakes trout (100 ng/g). Treatment kestrels had lower plasma thyroxine (T-4), plasma retinol, and hepatic retinol and retinyl palmitate concentrations, but unaltered triiodothyronine (T-3) concentrations and thyroid glandular structure. BDE-47, -100, and -99 were negatively associated with plasma T-4, plasma retinol (BDE-100, -99) and hepatic retinol (BDE-47). Despite an antioxidant-rich diet, PBDE exposure induced hepatic oxidative stress, particularly in females, with an increased hepatic GSSG:GSH ratio, a marginal increase in lipid peroxidation, and increased oxidized glutathione. Positive associations were found between concentrations of BDE-183 and thiols and, in males, between BDE-99 and reduced GSH, but a negative association occurred between BDE-99 and TBARS. Subsequently, concentrations of PBDE congeners in wild birds may alter thyroid hormone and vitamin A concentrations, glutathione metabolism and oxidative stress.

Unique expression of cytoskeletal proteins in human soft palate muscles.

Science.gov (United States)

Shah, Farhan; Berggren, Diana; Holmlund, Thorbjörn; Levring Jäghagen, Eva; Stål, Per

2016-03-01

The human oropharyngeal muscles have a unique anatomy with diverse and intricate functions. To investigate if this specialization is also reflected in the cytoarchitecture of muscle fibers, intermediate filament proteins and the dystrophin-associated protein complex have been analyzed in two human palate muscles, musculus uvula (UV) and musculus palatopharyngeus (PP), with immunohistochenmical and morphological techniques. Human limb muscles were used as reference. The findings show that the soft palate muscle fibers have a cytoskeletal architecture that differs from the limb muscles. While all limb muscles showed immunoreaction for a panel of antibodies directed against different domains of cytoskeletal proteins desmin and dystrophin, a subpopulation of palate muscle fibers lacked or had a faint immunoreaction for desmin (UV 11.7% and PP 9.8%) and the C-terminal of the dystrophin molecule (UV 4.2% and PP 6.4%). The vast majority of these fibers expressed slow contractile protein myosin heavy chain I. Furthermore, an unusual staining pattern was also observed in these fibers for β-dystroglycan, caveolin-3 and neuronal nitric oxide synthase nNOS, which are all membrane-linking proteins associated with the dystrophin C-terminus. While the immunoreaction for nNOS was generally weak or absent, β-dystroglycan and caveolin-3 showed a stronger immunostaining. The absence or a low expression of cytoskeletal proteins otherwise considered ubiquitous and important for integration and contraction of muscle cells indicate a unique cytoarchitecture designed to meet the intricate demands of the upper airway muscles. It can be concluded that a subgroup of muscle fibers in the human soft palate appears to have special biomechanical properties, and their unique cytoarchitecture must be taken into account while assessing function and pathology in oropharyngeal muscles. © 2015 Anatomical Society.

Levels and distribution of polybrominated diphenyl ethers in various tissues of birds of prey

International Nuclear Information System (INIS)

Voorspoels, Stefan; Covaci, Adrian; Lepom, Peter; Jaspers, Veerle L.B.; Schepens, Paul

2006-01-01

In the present study, concentrations and tissue distribution of polybrominated diphenyl ethers (PBDEs; IUPAC nos. 28, 47, 99, 100, 153, 154, 183, and 209) were examined in brain, adipose tissue, liver, muscle, and serum of birds of prey. Median ΣPBDE levels (BDE 28-183) in the tissues of sparrowhawks ranged from 360 to 1900 ng/g lipid weight (lw), which was in general one order of magnitude higher than in the tissues of common buzzards (26-130 ng/g lw). There were no differences in PBDE congener patterns between the various tissues within individuals of a certain species. Inter-species differences in PBDE patterns and in particular the percentage of BDE 99, 100 and 153 were, however, pronounced between sparrowhawk and common buzzard. BDE 209 was detected in nearly all serum and in some liver samples, but not in any other tissues. This observation suggests that exposure to BDE 209 is low or that this congener is poorly accumulated. Passive (lipid content related) diffusion could not completely describe the PBDE tissue distribution, e.g. the lowest PBDE-load was measured in brain, a fairly lipid rich tissue. - Distribution of polybrominated diphenyl ethers in birds of prey is tissue dependent

Cytoskeletal Configuration Modulates Mechanically Induced Changes in Mesenchymal Stem Cell Osteogenesis, Morphology, and Stiffness

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Pongkitwitoon, Suphannee; Uzer, Gunes; Rubin, Janet; Judex, Stefan

2016-10-01

Mesenchymal stem cells (MSC) responding to mechanical cues generated by physical activity is critical for skeletal development and remodeling. Here, we utilized low intensity vibrations (LIV) as a physiologically relevant mechanical signal and hypothesized that the confined cytoskeletal configuration imposed by 2D culture will enable human bone marrow MSCs (hBMSC) to respond more robustly when LIV is applied in-plane (horizontal-LIV) rather than out-of-plane (vertical-LIV). All LIV signals enhanced hBMSC proliferation, osteogenic differentiation, and upregulated genes associated with cytoskeletal structure. The cellular response was more pronounced at higher frequencies (100 Hz vs 30 Hz) and when applied in the horizontal plane. Horizontal but not vertical LIV realigned the cell cytoskeleton, culminating in increased cell stiffness. Our results show that applying very small oscillatory motions within the primary cell attachment plane, rather than perpendicular to it, amplifies the cell’s response to LIV, ostensibly facilitating a more effective transfer of intracellular forces. Transcriptional and structural changes in particular with horizontal LIV, together with the strong frequency dependency of the signal, emphasize the importance of intracellular cytoskeletal configuration in sensing and responding to high-frequency mechanical signals at low intensities.

Vacuolar and cytoskeletal dynamics during elicitor-induced programmed cell death in tobacco BY-2 cells.

Science.gov (United States)

Higaki, Takumi; Kadota, Yasuhiro; Goh, Tatsuaki; Hayashi, Teruyuki; Kutsuna, Natsumaro; Sano, Toshio; Hasezawa, Seiichiro; Kuchitsu, Kazuyuki

2008-09-01

Responses of plant cells to environmental stresses often involve morphological changes, differentiation and redistribution of various organelles and cytoskeletal network. Tobacco BY-2 cells provide excellent model system for in vivo imaging of these intracellular events. Treatment of the cell cycle-synchronized BY-2 cells with a proteinaceous oomycete elicitor, cryptogein, induces highly synchronous programmed cell death (PCD) and provide a model system to characterize vacuolar and cytoskeletal dynamics during the PCD. Sequential observation revealed dynamic reorganization of the vacuole and actin microfilaments during the execution of the PCD. We further characterized the effects cryptogein on mitotic microtubule organization in cell cycle-synchronized cells. Cryptogein treatment at S phase inhibited formation of the preprophase band, a cortical microtubule band that predicts the cell division site. Cortical microtubules kept their random orientation till their disruption that gradually occurred during the execution of the PCD twelve hours after the cryptogein treatment. Possible molecular mechanisms and physiological roles of the dynamic behavior of the organelles and cytoskeletal network in the pathogenic signal-induced PCD are discussed.

VEGF-A, cytoskeletal dynamics, and the pathological vascular phenotype

International Nuclear Information System (INIS)

Nagy, Janice A.; Senger, Donald R.

2006-01-01

Normal angiogenesis is a complex process involving the organization of proliferating and migrating endothelial cells (ECs) into a well-ordered and highly functional vascular network. In contrast, pathological angiogenesis, which is a conspicuous feature of tumor growth, ischemic diseases, and chronic inflammation, is characterized by vessels with aberrant angioarchitecture and compromised barrier function. Herein we review the subject of pathological angiogenesis, particularly that driven by vascular endothelial growth factor (VEGF-A), from a new perspective. We propose that the serious structural and functional anomalies associated with VEGF-A-elicited neovessels, reflect, at least in part, imbalances in the internal molecular cues that govern the ordered assembly of ECs into three dimensional vascular networks and preserve vessel barrier function. Adopting such a viewpoint widens the focus from solely on specific pro-angiogenic stimuli such as VEGF-A to include a key set of cytoskeletal regulatory molecules, the Rho GTPases, which are known to direct multiple aspects of vascular morphogenesis including EC motility, alignment, multi-cellular organization, as well as intercellular junction integrity. We offer this perspective to draw attention to the importance of endothelial cytoskeletal dynamics for proper neovascularization and to suggest new therapeutic strategies with the potential to improve the pathological vascular phenotype

Vitreous-induced cytoskeletal rearrangements via the Rac1 GTPase-dependent signaling pathway in human retinal pigment epithelial cells

International Nuclear Information System (INIS)

Huang, Xionggao; Wei, Yantao; Ma, Haizhi; Zhang, Shaochong

2012-01-01

Highlights: ► Vitreous induces morphological changes and cytoskeletal rearrangements in RPE cells. ► Rac1 is activated in vitreous-transformed RPE cells. ► Rac inhibition prevents morphological changes in vitreous-transformed RPE cells. ► Rac inhibition suppresses cytoskeletal rearrangements in vitreous-transformed RPE cells. ► The vitreous-induced effects are mediated by a Rac1 GTPase/LIMK1/cofilin pathway. -- Abstract: Proliferative vitreoretinopathy (PVR) is mainly caused by retinal pigment epithelial (RPE) cell migration, invasion, proliferation and transformation into fibroblast-like cells that produce the extracellular matrix (ECM). The vitreous humor is known to play an important role in PVR. An epithelial-to-mesenchymal transdifferentiation (EMT) of human RPE cells induced by 25% vitreous treatment has been linked to stimulation of the mesenchymal phenotype, migration and invasion. Here, we characterized the effects of the vitreous on the cell morphology and cytoskeleton in human RPE cells. The signaling pathway that mediates these effects was investigated. Serum-starved RPE cells were incubated with 25% vitreous, and the morphological changes were examined by phase-contrast microscopy. Filamentous actin (F-actin) was examined by immunofluorescence and confocal microscopy. Protein phosphorylation of AKT, ERK1/2, Smad2/3, LIM kinase (LIMK) 1 and cofilin was analyzed by Western blot analysis. Vitreous treatment induced cytoskeletal rearrangements, activated Rac1 and enhanced the phosphorylation of AKT, ERK1/2 and Smad2/3. When the cells were treated with a Rac activation-specific inhibitor, the cytoskeletal rearrangements were prevented, and the phosphorylation of Smad2/3 was blocked. Vitreous treatment also enhanced the phosphorylation of LIMK1 and cofilin and the Rac inhibitor blocked this effect. We propose that vitreous-transformed human RPE cells undergo cytoskeletal rearrangements via Rac1 GTPase-dependent pathways that modulate LIMK1 and

Vitreous-induced cytoskeletal rearrangements via the Rac1 GTPase-dependent signaling pathway in human retinal pigment epithelial cells

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Huang, Xionggao [State Key Ophthalmic Laboratory, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou (China); Department of Ophthalmology, Hainan Medical College, Haikou (China); Wei, Yantao; Ma, Haizhi [State Key Ophthalmic Laboratory, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou (China); Zhang, Shaochong, E-mail: zhshaochong@163.com [State Key Ophthalmic Laboratory, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou (China)

2012-03-09

Highlights: Black-Right-Pointing-Pointer Vitreous induces morphological changes and cytoskeletal rearrangements in RPE cells. Black-Right-Pointing-Pointer Rac1 is activated in vitreous-transformed RPE cells. Black-Right-Pointing-Pointer Rac inhibition prevents morphological changes in vitreous-transformed RPE cells. Black-Right-Pointing-Pointer Rac inhibition suppresses cytoskeletal rearrangements in vitreous-transformed RPE cells. Black-Right-Pointing-Pointer The vitreous-induced effects are mediated by a Rac1 GTPase/LIMK1/cofilin pathway. -- Abstract: Proliferative vitreoretinopathy (PVR) is mainly caused by retinal pigment epithelial (RPE) cell migration, invasion, proliferation and transformation into fibroblast-like cells that produce the extracellular matrix (ECM). The vitreous humor is known to play an important role in PVR. An epithelial-to-mesenchymal transdifferentiation (EMT) of human RPE cells induced by 25% vitreous treatment has been linked to stimulation of the mesenchymal phenotype, migration and invasion. Here, we characterized the effects of the vitreous on the cell morphology and cytoskeleton in human RPE cells. The signaling pathway that mediates these effects was investigated. Serum-starved RPE cells were incubated with 25% vitreous, and the morphological changes were examined by phase-contrast microscopy. Filamentous actin (F-actin) was examined by immunofluorescence and confocal microscopy. Protein phosphorylation of AKT, ERK1/2, Smad2/3, LIM kinase (LIMK) 1 and cofilin was analyzed by Western blot analysis. Vitreous treatment induced cytoskeletal rearrangements, activated Rac1 and enhanced the phosphorylation of AKT, ERK1/2 and Smad2/3. When the cells were treated with a Rac activation-specific inhibitor, the cytoskeletal rearrangements were prevented, and the phosphorylation of Smad2/3 was blocked. Vitreous treatment also enhanced the phosphorylation of LIMK1 and cofilin and the Rac inhibitor blocked this effect. We propose that vitreous

Magnolol inhibits migration of vascular smooth muscle cells via cytoskeletal remodeling pathway to attenuate neointima formation

International Nuclear Information System (INIS)

Karki, Rajendra; Kim, Seong-Bin; Kim, Dong-Wook

2013-01-01

Background: Increased proliferation and migration of vascular smooth muscle cells (VSMCs) contribute importantly to the formation of both atherosclerotic and restenotic lesions. The objective of this study was to investigate the effect of magnolol on VSMC migration. Methods: The proteolytic activity of matrix metalloproteinases (MMPs) in tumor necrosis factor alpha (TNF-α) stimulated VSMCs was performed by gelatin zymography. VSMC migration was assessed by wound healing and Boyden chamber methods. Collagen induced VSMC adhesion was determined by spectrofluorimeter and stress fibers formation was evaluated by fluorescence microscope. The expression of signaling molecules involved in stress fibers formation was determined by western blot. The phosphorylation of myosin light chain (MLC20) was determined by urea-glycerol polyacrylamide gel electrophoresis. Immunohistochemistry was performed to determine the expression of β1-integrin and collagen type I in the injured carotid arteries of rats on day 35 after vascular injury. Results: VSMC migration was strongly inhibited by magnolol without affecting MMPs expression. Also, magnolol inhibited β1-integrin expression, FAK phosphorylation and RhoA and Cdc42 activation to inhibit the collagen induced stress fibers formation. Moreover, magnolol inhibited the phosphorylation of MLC20. Our in vivo results showed that magnolol inhibited β1-integrin expression, collagen type I deposition and FAK phosphorylation in injured carotid arteries without affecting MMP-2 activity. Conclusions: Magnolol inhibited VSMC migration via inhibition of cytoskeletal remodeling pathway to attenuate neointima formation. General significance: This study provides a rationale for further evaluation of magnolol for the management of atherosclerosis and restenosis. - Highlights: • Magnolol strongly inhibited migration of VSMCs. • Magnolol inhibited stress fibers formation. • MLC20 phosphorylation was also inhibited by magnolol. • Anti

Magnolol inhibits migration of vascular smooth muscle cells via cytoskeletal remodeling pathway to attenuate neointima formation

Energy Technology Data Exchange (ETDEWEB)

Karki, Rajendra [Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City (United States); Department of Oriental Medicine Resources, Mokpo National University (Korea, Republic of); Kim, Seong-Bin [Jeollanamdo Development Institute for Korean Traditional Medicine, Jangheung gun, Jeollanamdo (Korea, Republic of); Kim, Dong-Wook, E-mail: dbkim@mokpo.ac.kr [Department of Oriental Medicine Resources, Mokpo National University (Korea, Republic of)

2013-12-10

Background: Increased proliferation and migration of vascular smooth muscle cells (VSMCs) contribute importantly to the formation of both atherosclerotic and restenotic lesions. The objective of this study was to investigate the effect of magnolol on VSMC migration. Methods: The proteolytic activity of matrix metalloproteinases (MMPs) in tumor necrosis factor alpha (TNF-α) stimulated VSMCs was performed by gelatin zymography. VSMC migration was assessed by wound healing and Boyden chamber methods. Collagen induced VSMC adhesion was determined by spectrofluorimeter and stress fibers formation was evaluated by fluorescence microscope. The expression of signaling molecules involved in stress fibers formation was determined by western blot. The phosphorylation of myosin light chain (MLC20) was determined by urea-glycerol polyacrylamide gel electrophoresis. Immunohistochemistry was performed to determine the expression of β1-integrin and collagen type I in the injured carotid arteries of rats on day 35 after vascular injury. Results: VSMC migration was strongly inhibited by magnolol without affecting MMPs expression. Also, magnolol inhibited β1-integrin expression, FAK phosphorylation and RhoA and Cdc42 activation to inhibit the collagen induced stress fibers formation. Moreover, magnolol inhibited the phosphorylation of MLC20. Our in vivo results showed that magnolol inhibited β1-integrin expression, collagen type I deposition and FAK phosphorylation in injured carotid arteries without affecting MMP-2 activity. Conclusions: Magnolol inhibited VSMC migration via inhibition of cytoskeletal remodeling pathway to attenuate neointima formation. General significance: This study provides a rationale for further evaluation of magnolol for the management of atherosclerosis and restenosis. - Highlights: • Magnolol strongly inhibited migration of VSMCs. • Magnolol inhibited stress fibers formation. • MLC20 phosphorylation was also inhibited by magnolol. • Anti

The regulation of cytoskeletal and liver-specific gene expression during liver regeneration and primary hepatocyte culture

International Nuclear Information System (INIS)

Robinson, G.S.

1989-01-01

The focus of this dissertation is to determine what role(s) the extracellular matrix and expression of certain cytoskeletal genes play in the regulation of hepatocyte growth and the maintenance of a differential state. The expression of several cytoskeletal and liver-specific genes was examined during liver regeneration and in hepatocyte cultures maintained in a hormonally-defined, serum-free medium and plated on two different matrices: rat tail collagen and the EHS matrix. During liver regeneration and in hepatocytes cultured on rat tail collagen, there was a dramatic increase in tubulin mRNA levels coincident with but not linked to DNA synthesis. The message levels for other cytoskeletal genes similarly increased, while a decrease was observed in the mRNA levels of the liver-specific genes, serum albumin and alpha 1 inhibitor III. Hepatocytes cultured on the EHS matrix resulted in the maintenance of low levels of cytoskeletal gene expression and high levels of liver-specific gene expression, similar to that observed in the normal liver. Results from subcellar fractionation and two-dimensional gel electrophoresis of 35 S-labelled proteins paralleled the results seen at the mRNA level. Preliminary work suggests that microtubule organization may play a role in the expression of the liver-specific genes which encode secreted proteins. These studies, which compare hepatocytes cultured on collagen or the EHS matrix gel, reveal that both cell-cell and cell-matrix interactions play a major role in the maintenance of the differential phenotype in hepatocytes

Biomonitoring of Danish school children and mothers including biomarkers of PBDE and glyphosate

DEFF Research Database (Denmark)

Knudsen, Lisbeth E.; Hansen, Pernille Winton; Mizrak, Seher

2017-01-01

Danish school children aged 6–11 years and their mothers from rural and urban areas in autumn 2011. Some – but not all – results were published; however, the concurrence of the chemicals has not been assessed. Methods: The measured concentrations of polybrominated diphenyl ethers (PBDEs) and glyphosate...... is assessed to complete the investigation of all 66 chemicals in DEMOCOPHES. The concentrations of PBDEs were measured in plasma samples of 143 mothers and 116 children. Glyphosate was measured in a subsample of 27 urine samples. Previously assessed chemicals were polychlorinated biphenyls (PCBs...... the concentrations of the different environmental chemicals. investigated by correlation analysis. Results: PBDE47 was found in relatively high levels compared with previous Danish results in both mothers and children, with a significantly higher level in the children compared to their mothers. Glyphosate...

p21-Activated kinase (PAK regulates cytoskeletal reorganization and directional migration in human neutrophils.

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Asako Itakura

Full Text Available Neutrophils serve as a first line of defense in innate immunity owing in part to their ability to rapidly migrate towards chemotactic factors derived from invading pathogens. As a migratory function, neutrophil chemotaxis is regulated by the Rho family of small GTPases. However, the mechanisms by which Rho GTPases orchestrate cytoskeletal dynamics in migrating neutrophils remain ill-defined. In this study, we characterized the role of p21-activated kinase (PAK downstream of Rho GTPases in cytoskeletal remodeling and chemotactic processes of human neutrophils. We found that PAK activation occurred upon stimulation of neutrophils with f-Met-Leu-Phe (fMLP, and PAK accumulated at the actin-rich leading edge of stimulated neutrophils, suggesting a role for PAK in Rac-dependent actin remodeling. Treatment with the pharmacological PAK inhibitor, PF3758309, abrogated the integrity of RhoA-mediated actomyosin contractility and surface adhesion. Moreover, inhibition of PAK activity impaired neutrophil morphological polarization and directional migration under a gradient of fMLP, and was associated with dysregulated Ca(2+ signaling. These results suggest that PAK serves as an important effector of Rho-family GTPases in neutrophil cytoskeletal reorganization, and plays a key role in driving efficient directional migration of human neutrophils.

Polybrominated diphenyl ethers in water, sediment, soil, and biological samples from different industrial areas in Zhejiang, China

International Nuclear Information System (INIS)

Wang, Junxia; Lin, Zhenkun; Lin, Kuangfei; Wang, Chunyan; Zhang, Wei; Cui, Changyuan; Lin, Junda; Dong, Qiaoxiang; Huang, Changjiang

2011-01-01

Highlights: ► We examined PBDE concentrations in various matrices from different industrial areas. ► Elevated PBDE levels were found in areas with low-voltage electrical manufactures. ► Areas with e-waste recycling activities also had higher PBDE concentrations. ► PBDE content and composition in water samples varied from one area to another. ► PBDE composition in sediment/soil and biological samples was predominated by BDE-209. - Abstract: Polybrominated diphenyl ethers (PBDEs) have been used extensively in electrical and electronic products, but little is known about their distribution in the environment surrounding the manufacturing factories. This study reports PBDE contamination in various matrices from the location (Liushi, Zhejiang province) that produces more than 70% of the low-voltage electrical appliances in China. Additionally, PBDE contamination was compared with other industries such as the e-waste recycling business (Fengjiang) in the same region. Specifically, we measured seven PBDE congeners (BDEs – 47, 99, 100, 153, 154, 183, and 209) in water, sediment, soil, plant, and animal tissues from four different areas in this region. The present study revealed elevated PBDE concentrations in all matrices collected from Liushi and Fengjiang in comparison with highly industrialized areas without significant PBDE contamination sources. In water samples, there were large variations of PBDE content and composition across different areas. In sediment/soil and biological samples, BDE-209 was the predominant congener and this could be due to the abundant usage of deca-BDE mixtures in China. Our findings provide the very first data on PBDE contamination in the local environments surrounding the electronics industry, and also reveal widespread PBDE contamination in highly industrialized coastal regions of China.

Cytoskeletal Reorganization Drives Mesenchymal Condensation and Regulates Downstream Molecular Signaling.

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Poulomi Ray

Full Text Available Skeletal condensation occurs when specified mesenchyme cells self-organize over several days to form a distinctive cartilage template. Here, we determine how and when specified mesenchyme cells integrate mechanical and molecular information from their environment, forming cartilage condensations in the pharyngeal arches of chick embryos. By disrupting cytoskeletal reorganization, we demonstrate that dynamic cell shape changes drive condensation and modulate the response of the condensing cells to Fibroblast Growth Factor (FGF, Bone Morphogenetic Protein (BMP and Transforming Growth Factor beta (TGF-β signaling pathways. Rho Kinase (ROCK-driven actomyosin contractions and Myosin II-generated differential cell cortex tension regulate these cell shape changes. Disruption of the condensation process inhibits the differentiation of the mesenchyme cells into chondrocytes, demonstrating that condensation regulates the fate of the mesenchyme cells. We also find that dorsal and ventral condensations undergo distinct cell shape changes. BMP signaling is instructive for dorsal condensation-specific cell shape changes. Moreover, condensations exhibit ventral characteristics in the absence of BMP signaling, suggesting that in the pharyngeal arches ventral morphology is the ground pattern. Overall, this study characterizes the interplay between cytoskeletal dynamics and molecular signaling in a self-organizing system during tissue morphogenesis.

Rechargeable sup(99)MO/sup(99m)TC generator system

International Nuclear Information System (INIS)

Thornton, A.K.; Cerone, F.E.

1980-01-01

A rechargeable radioisotope generator system is described in which the transfer of the parent isotope, molybdenum 99, can be affected safely and easily. Part of the system consists of a shielded shipping vial for the parent isotope. The generator consists of an alumina column upon which molybdenum 99 may be adsorbed and from which technetium 99m may be eluted. The generator is shipped as a cold package to the user and is charged as needed. A transfer mechanism is incorporated in the shipping shield, which allows the septum of the vial to be pierced and the contents to be transferred to the generator essentially automatically. (LL)

Cytoskeletal Tropomyosin Tm5NM1 Is Required for Normal Excitation–Contraction Coupling in Skeletal Muscle

Science.gov (United States)

Vlahovich, Nicole; Kee, Anthony J.; Van der Poel, Chris; Kettle, Emma; Hernandez-Deviez, Delia; Lucas, Christine; Lynch, Gordon S.; Parton, Robert G.; Gunning, Peter W.

2009-01-01

The functional diversity of the actin microfilaments relies in part on the actin binding protein tropomyosin (Tm). The muscle-specific Tms regulate actin-myosin interactions and hence contraction. However, there is less known about the roles of the numerous cytoskeletal isoforms. We have shown previously that a cytoskeletal Tm, Tm5NM1, defines a Z-line adjacent cytoskeleton in skeletal muscle. Recently, we identified a second cytoskeletal Tm in this region, Tm4. Here we show that Tm4 and Tm5NM1 define separate actin filaments; the former associated with the terminal sarcoplasmic reticulum (SR) and other tubulovesicular structures. In skeletal muscles of Tm5NM1 knockout (KO) mice, Tm4 localization was unchanged, demonstrating the specificity of the membrane association. Tm5NM1 KO muscles exhibit potentiation of T-system depolarization and decreased force rundown with repeated T-tubule depolarizations consistent with altered T-tubule function. These results indicate that a Tm5NM1-defined actin cytoskeleton is required for the normal excitation–contraction coupling in skeletal muscle. PMID:19005216

Cytoskeletal tropomyosin Tm5NM1 is required for normal excitation-contraction coupling in skeletal muscle.

Science.gov (United States)

Vlahovich, Nicole; Kee, Anthony J; Van der Poel, Chris; Kettle, Emma; Hernandez-Deviez, Delia; Lucas, Christine; Lynch, Gordon S; Parton, Robert G; Gunning, Peter W; Hardeman, Edna C

2009-01-01

The functional diversity of the actin microfilaments relies in part on the actin binding protein tropomyosin (Tm). The muscle-specific Tms regulate actin-myosin interactions and hence contraction. However, there is less known about the roles of the numerous cytoskeletal isoforms. We have shown previously that a cytoskeletal Tm, Tm5NM1, defines a Z-line adjacent cytoskeleton in skeletal muscle. Recently, we identified a second cytoskeletal Tm in this region, Tm4. Here we show that Tm4 and Tm5NM1 define separate actin filaments; the former associated with the terminal sarcoplasmic reticulum (SR) and other tubulovesicular structures. In skeletal muscles of Tm5NM1 knockout (KO) mice, Tm4 localization was unchanged, demonstrating the specificity of the membrane association. Tm5NM1 KO muscles exhibit potentiation of T-system depolarization and decreased force rundown with repeated T-tubule depolarizations consistent with altered T-tubule function. These results indicate that a Tm5NM1-defined actin cytoskeleton is required for the normal excitation-contraction coupling in skeletal muscle.

Polybrominated diphenyl ethers in water, sediment, soil, and biological samples from different industrial areas in Zhejiang, China

Energy Technology Data Exchange (ETDEWEB)

Wang, Junxia; Lin, Zhenkun [Zhejiang Provincial Key Lab for Technology and Application of Model Organisms, Institute of Watershed Science and Environmental Ecology, Wenzhou Medical College, Wenzhou 325035 (China); Lin, Kuangfei [School of Resources and Environmental Engineering, East China University of Science and Technology/State Environmental Protection Key Laboratory of Environmental Risk Assessment and Control on Chemical Process, Shanghai 200237 (China); Wang, Chunyan [Zhejiang Provincial Key Lab for Technology and Application of Model Organisms, Institute of Watershed Science and Environmental Ecology, Wenzhou Medical College, Wenzhou 325035 (China); Zhang, Wei [School of Resources and Environmental Engineering, East China University of Science and Technology/State Environmental Protection Key Laboratory of Environmental Risk Assessment and Control on Chemical Process, Shanghai 200237 (China); Cui, Changyuan [Zhejiang Provincial Key Lab for Technology and Application of Model Organisms, Institute of Watershed Science and Environmental Ecology, Wenzhou Medical College, Wenzhou 325035 (China); Lin, Junda [Department of Biological Sciences, Florida Institute of Technology, Melbourne, FL 32901 (United States); Dong, Qiaoxiang, E-mail: dqxdong@163.com [Zhejiang Provincial Key Lab for Technology and Application of Model Organisms, Institute of Watershed Science and Environmental Ecology, Wenzhou Medical College, Wenzhou 325035 (China); Huang, Changjiang, E-mail: cjhuang5711@163.com [Zhejiang Provincial Key Lab for Technology and Application of Model Organisms, Institute of Watershed Science and Environmental Ecology, Wenzhou Medical College, Wenzhou 325035 (China)

2011-12-15

Highlights: Black-Right-Pointing-Pointer We examined PBDE concentrations in various matrices from different industrial areas. Black-Right-Pointing-Pointer Elevated PBDE levels were found in areas with low-voltage electrical manufactures. Black-Right-Pointing-Pointer Areas with e-waste recycling activities also had higher PBDE concentrations. Black-Right-Pointing-Pointer PBDE content and composition in water samples varied from one area to another. Black-Right-Pointing-Pointer PBDE composition in sediment/soil and biological samples was predominated by BDE-209. - Abstract: Polybrominated diphenyl ethers (PBDEs) have been used extensively in electrical and electronic products, but little is known about their distribution in the environment surrounding the manufacturing factories. This study reports PBDE contamination in various matrices from the location (Liushi, Zhejiang province) that produces more than 70% of the low-voltage electrical appliances in China. Additionally, PBDE contamination was compared with other industries such as the e-waste recycling business (Fengjiang) in the same region. Specifically, we measured seven PBDE congeners (BDEs - 47, 99, 100, 153, 154, 183, and 209) in water, sediment, soil, plant, and animal tissues from four different areas in this region. The present study revealed elevated PBDE concentrations in all matrices collected from Liushi and Fengjiang in comparison with highly industrialized areas without significant PBDE contamination sources. In water samples, there were large variations of PBDE content and composition across different areas. In sediment/soil and biological samples, BDE-209 was the predominant congener and this could be due to the abundant usage of deca-BDE mixtures in China. Our findings provide the very first data on PBDE contamination in the local environments surrounding the electronics industry, and also reveal widespread PBDE contamination in highly industrialized coastal regions of China.

Attenuation of LDHA expression in cancer cells leads to redox-dependent alterations in cytoskeletal structure and cell migration.

Science.gov (United States)

Arseneault, Robert; Chien, Andrew; Newington, Jordan T; Rappon, Tim; Harris, Richard; Cumming, Robert C

2013-09-28

Aerobic glycolysis, the preferential use of glycolysis even in the presence of oxygen to meet cellular metabolic demands, is a near universal feature of cancer. This unique type of metabolism is thought to protect cancer cells from damaging reactive oxygen species (ROS) produced in the mitochondria. Using the cancer cell line MDA-MB-435 it is shown that shRNA mediated knockdown of lactate dehydrogenase A (LDHA), a key mediator of aerobic glycolysis, results in elevated mitochondrial ROS production and a concomitant decrease in cell proliferation and motility. Redox-sensitive proteins affected by oxidative stress associated with LDHA knockdown were identified by Redox 2D-PAGE and mass spectrometry. In particular, tropomyosin (Tm) isoforms Tm4, Tm5NM1 and Tm5NM5, proteins involved in cell migration and cytoskeletal dynamics, exhibited changes in disulfide bonding and co-localized with peri-nuclear actin aggregates in LDHA knockdown cells. In contrast, treatment with the thiol-based antioxidant N-acetylcysteine promoted the relocalization of Tms to cortical actin microfilaments and partially rescued the migration defects associated with attenuated LDHA expression. These results suggest that aerobic glycolysis and reduced mitochondrial ROS production create an environment conducive to cytoskeletal remodeling; key events linked to the high cell motility associated with cancer. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The phosphorylation status and cytoskeletal remodeling of striatal astrocytes treated with quinolinic acid

International Nuclear Information System (INIS)

Pierozan, Paula; Ferreira, Fernanda; Ortiz de Lima, Bárbara; Gonçalves Fernandes, Carolina; Totarelli Monteforte, Priscila; Castro Medaglia, Natalia de; Bincoletto, Claudia; Soubhi Smaili, Soraya; Pessoa-Pureur, Regina

2014-01-01

Quinolinic acid (QUIN) is a glutamate agonist which markedly enhances the vulnerability of neural cells to excitotoxicity. QUIN is produced from the amino acid tryptophan through the kynurenine pathway (KP). Dysregulation of this pathway is associated with neurodegenerative conditions. In this study we treated striatal astrocytes in culture with QUIN and assayed the endogenous phosphorylating system associated with glial fibrillary acidic protein (GFAP) and vimentin as well as cytoskeletal remodeling. After 24 h incubation with 100 µM QUIN, cells were exposed to 32 P-orthophosphate and/or protein kinase A (PKA), protein kinase dependent of Ca 2+ /calmodulin II (PKCaMII) or protein kinase C (PKC) inhibitors, H89 (20 μM), KN93 (10 μM) and staurosporin (10 nM), respectively. Results showed that hyperphosphorylation was abrogated by PKA and PKC inhibitors but not by the PKCaMII inhibitor. The specific antagonists to ionotropic NMDA and non-NMDA (50 µM DL-AP5 and CNQX, respectively) glutamate receptors as well as to metabotropic glutamate receptor (mGLUR; 50 µM MCPG), mGLUR1 (100 µM MPEP) and mGLUR5 (10 µM 4C3HPG) prevented the hyperphosphorylation provoked by QUIN. Also, intra and extracellular Ca 2+ quelators (1 mM EGTA; 10 µM BAPTA-AM, respectively) prevented QUIN-mediated effect, while Ca 2+ influx through voltage-dependent Ca 2+ channel type L (L-VDCC) (blocker: 10 µM verapamil) is not implicated in this effect. Morphological analysis showed dramatically altered actin cytoskeleton with concomitant change of morphology to fusiform and/or flattened cells with retracted cytoplasm and disruption of the GFAP meshwork, supporting misregulation of actin cytoskeleton. Both hyperphosphorylation and cytoskeletal remodeling were reversed 24 h after QUIN removal. Astrocytes are highly plastic cells and the vulnerability of astrocyte cytoskeleton may have important implications for understanding the neurotoxicity of QUIN in neurodegenerative disorders. - Highlights: �

Dietary exposure of juvenile common sole (Solea solea L.) to polybrominated diphenyl ethers (PBDEs): Part 1. Bioaccumulation and elimination kinetics of individual congeners and their debrominated metabolites

International Nuclear Information System (INIS)

Munschy, C.; Heas-Moisan, K.; Tixier, C.; Olivier, N.; Gastineau, O.; Le Bayon, N.; Buchet, V.

2011-01-01

The uptake and elimination of six PBDE congeners (BDE-28, -47, -99, -100, -153, -209) were studied in juvenile common sole (Solea solea L.) exposed to spiked contaminated food over a three-month period, then depurated over a five-month period. The results show that all of the studied PBDEs accumulate in fish tissues, including the higher brominated congener BDE-209. Several additional PBDE congeners were identified in the tissues of exposed fish, revealing PBDE transformation, mainly via debromination. The identified congeners originating from PBDE debromination include BDE-49 and BDE-202 and a series of unidentified tetra-, penta-, and hepta- BDEs. Contaminant assimilation efficiencies (AEs) were related to their hydrophobicity (log K ow ) and influenced by PBDE biotransformation. Metabolism via debromination appears to be a major degradation route of PBDEs in juvenile sole in comparison to biotransformation into hydroxylated metabolites. - Juvenile sole exposed to artificially-contaminated food accumulate PBDEs, including the higher brominated congeners, and have a debromination capacity.

Effect of Rapid Chilling on Beef Quality and Cytoskeletal Protein Degradation in of Chinese Yellow Crossbred Bulls

Directory of Open Access Journals (Sweden)

Yanwei Mao

2012-08-01

Full Text Available The objective of this study was to investigate the effect of rapid chilling (RC on beef quality and the degradation of cytoskeletal proteins. Twenty Chinese Yellow crossbred bulls were selected and randomly divided into two groups. RC and conventional chilling (CC were applied to left and right sides of the carcasses respectively after slaughtering. To determine whether electrical stimulation (ES treatment can alleviate the potential hazard of RC on meat quality, ES was applied to one group. The effects of RC and ES were determined by meat color, shear force and cytoskeletal protein degradation postmortem (PM. The results showed that RC decreased beef tenderness at 1 d and 3 d postmortem, but had no detrimental effect on meat color. Western blotting showed that RC decreased the degradation rate of desmin and troponin-T, but the effects weakened gradually as postmortem aging extended. Degradation rates of both desmin and troponin-T were accelerated by ES. The combination of RC and ES could improve beef color, accelerate degradation rate of cytoskeletal protein and improve beef tenderness.

Novel Interactions between Gut Microbiome and Host Drug-Processing Genes Modify the Hepatic Metabolism of the Environmental Chemicals Polybrominated Diphenyl Ethers

Energy Technology Data Exchange (ETDEWEB)

Li, Cindy Yanfei; Lee, Soowan; Cade, Sara; Kuo, Li-Jung; Schultz, Irvin R.; Bhatt, Deepak K.; Prasad, Bhagwat; Bammler, Theo K.; Cui, Julia Yue

2017-09-01

The gut microbiome is a novel frontier in xenobiotic metabolism. Polybrominated diphenyl ethers (PBDEs), especially BDE-47 and BDE-99, are among the most abundant and persistent environmental contaminants that produce a variety of toxicities. Little is known about how the gut microbiome affects the hepatic metabolism of PBDEs and the PBDE-mediated regulation of drug-processing genes (DPGs) in vivo. The goal of this study was to determine the role of gut microbiome in modulating the hepatic biotransformation of PBDEs. Nine-week-old male C57BL/6J conventional (CV) or germ free (GF) mice were treated with vehicle, BDE-47 or BDE-99 (100 μmol/kg) for four days. Following BDE-47 treatment, GF mice had higher level of 5-OH-BDE-47 but lower levels of 4 other metabolites in liver than CV mice; whereas following BDE-99 treatment, GF mice had lower levels of 4 minor metabolites in liver than CV mice. RNA- Seq demonstrated that the hepatic expression of DPGs was regulated by both PBDEs and enterotypes. Under basal condition, the lack of gut microbiome up-regulated the Cyp2c subfamily but down-regulated the Cyp3a subfamily. Following PBDE exposure, certain DPGs were differentially regulated by PBDEs in a gut microbiome-dependent manner. Interestingly, the lack of gut microbiome augmented PBDE-mediated up- regulation of many DPGs, such as Cyp1a2 and Cyp3a11 in mouse liver, which was further confirmed by targeted metabolomics. The lack of gut microbiome also augmented the Cyp3a enzyme activity in liver. In conclusion, our study has unveiled a novel interaction between gut microbiome and the hepatic biotransformation of PBDEs.

Reorganization of the actin cytoskeleton via transcriptional regulation of cytoskeletal/focal adhesion genes by myocardin-related transcription factors (MRTFs/MAL/MKLs)

International Nuclear Information System (INIS)

Morita, Tsuyoshi; Mayanagi, Taira; Sobue, Kenji

2007-01-01

RhoA is a crucial regulator of stress fiber and focal adhesion formation through the activation of actin nucleation and polymerization. It also regulates the nuclear translocation of myocardin-related transcription factor-A and -B (MRTF-A/B, MAL or MKL 1/2), which are co-activators of serum response factor (SRF). In dominant-negative MRTF-A (DN-MRTF-A)-expressing NIH 3T3 cell lines, the expressions of several cytoskeletal/focal adhesion genes were down-regulated, and the formation of stress fiber and focal adhesion was severely diminished. MRTF-A/B-knockdown cells also exhibited such cytoskeletal defects. In reporter assays, both RhoA and MRTF-A enhanced promoter activities of these genes in a CArG-box-dependent manner, and DN-MRTF-A inhibited the RhoA-mediated activation of these promoters. In dominant-negative RhoA (RhoA-N19)-expressing NIH 3T3 cell lines, the nuclear translocation of MRTF-A/B was predominantly prevented, resulting in the reduced expression of cytoskeletal/focal adhesion proteins. Further, constitutive-active MRTF-A/B increased the expression of endogenous cytoskeletal/focal adhesion proteins, and thereby rescued the defective phenotype of stress fibers and focal adhesions in RhoA-N19 expressing cells. These results indicate that MRTF-A/B act as pivotal mediators of stress fiber and focal adhesion formation via the transcriptional regulation of a subset of cytoskeletal/focal adhesion genes

Investigation of factors affecting adhesion of 99Tcm labelled colloids to glass vials

International Nuclear Information System (INIS)

Elliott, A.T.; Murray, T.; Hilditch, T.E.; Whateley, T.L.

1990-01-01

Factors which may possibly influence the adhesion of 99 Tc m labelled colloid to glass vials were investigated. Of five colloids studied, two protein-free tin colloids were affected most by the problem, some 12-18% being lost by adhesion to the glass vial when the colloid was left resting on the bench, or 60-87% when it was rotated for a period of 4 h. The proportion of activity which adhered to the vial was dependent on the time the product had been contained within it, whether on the bench or rotated. Two of the colloids, both of which contained protein, were affected only slightly by the problem, one being a tin colloid and the other a sulphur colloid. An antimony sulphide colloid, which contained no added protein, was virtually unaffected by the problem. The degree of adhesion was not related to the pH of the product, or to the temperature at which the product was stored, nor to the tendency of the colloidal particles to grow in size upon vigorous agitation. (author)

Biosynthesis of intestinal microvillar proteins. Rapid expression of cytoskeletal components in microvilli of pig small intestinal mucosal explants

DEFF Research Database (Denmark)

Cowell, G M; Danielsen, E M

1984-01-01

Using alkaline extraction to separate cytoskeletal and membrane proteins of intestinal microvilli, the kinetics of assembly of these two microvillar protein compartments was studied by pulse-chase labelling of pig small intestinal mucosal explants, kept in organ culture. Following a 10 min pulse...... of [35S]methionine, the membrane proteins did not appear in the microvillar fraction until after 40-60 min of chase. In contrast, the cytoskeletal components, of which the 110-kDa protein and villin were immunologically identified, were expressed in the microvillar fraction immediately after the 10 min...

The phosphorylation status and cytoskeletal remodeling of striatal astrocytes treated with quinolinic acid

Energy Technology Data Exchange (ETDEWEB)

Pierozan, Paula; Ferreira, Fernanda; Ortiz de Lima, Bárbara; Gonçalves Fernandes, Carolina [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003 (Brazil); Totarelli Monteforte, Priscila; Castro Medaglia, Natalia de; Bincoletto, Claudia; Soubhi Smaili, Soraya [Departamento de Farmacologia, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, SP (Brazil); Pessoa-Pureur, Regina, E-mail: rpureur@ufrgs.br [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003 (Brazil)

2014-04-01

Quinolinic acid (QUIN) is a glutamate agonist which markedly enhances the vulnerability of neural cells to excitotoxicity. QUIN is produced from the amino acid tryptophan through the kynurenine pathway (KP). Dysregulation of this pathway is associated with neurodegenerative conditions. In this study we treated striatal astrocytes in culture with QUIN and assayed the endogenous phosphorylating system associated with glial fibrillary acidic protein (GFAP) and vimentin as well as cytoskeletal remodeling. After 24 h incubation with 100 µM QUIN, cells were exposed to {sup 32}P-orthophosphate and/or protein kinase A (PKA), protein kinase dependent of Ca{sup 2+}/calmodulin II (PKCaMII) or protein kinase C (PKC) inhibitors, H89 (20 μM), KN93 (10 μM) and staurosporin (10 nM), respectively. Results showed that hyperphosphorylation was abrogated by PKA and PKC inhibitors but not by the PKCaMII inhibitor. The specific antagonists to ionotropic NMDA and non-NMDA (50 µM DL-AP5 and CNQX, respectively) glutamate receptors as well as to metabotropic glutamate receptor (mGLUR; 50 µM MCPG), mGLUR1 (100 µM MPEP) and mGLUR5 (10 µM 4C3HPG) prevented the hyperphosphorylation provoked by QUIN. Also, intra and extracellular Ca{sup 2+} quelators (1 mM EGTA; 10 µM BAPTA-AM, respectively) prevented QUIN-mediated effect, while Ca{sup 2+} influx through voltage-dependent Ca{sup 2+} channel type L (L-VDCC) (blocker: 10 µM verapamil) is not implicated in this effect. Morphological analysis showed dramatically altered actin cytoskeleton with concomitant change of morphology to fusiform and/or flattened cells with retracted cytoplasm and disruption of the GFAP meshwork, supporting misregulation of actin cytoskeleton. Both hyperphosphorylation and cytoskeletal remodeling were reversed 24 h after QUIN removal. Astrocytes are highly plastic cells and the vulnerability of astrocyte cytoskeleton may have important implications for understanding the neurotoxicity of QUIN in neurodegenerative

Distribution of polybrominated diphenyl ethers in Japanese autopsy tissue and body fluid samples.

Science.gov (United States)

Hirai, Tetsuya; Fujimine, Yoshinori; Watanabe, Shaw; Nakano, Takeshi

2012-09-01

Brominated flame retardants are components of many plastics and are used in products such as cars, textiles, televisions, and personal computers. Human exposure to polybrominated diphenyl ether (PBDE) flame retardants has increased exponentially during the last three decades. Our objective was to measure the body burden and distribution of PBDEs and to determine the concentrations of the predominant PBDE congeners in samples of liver, bile, adipose tissue, and blood obtained from Japanese autopsy cases. Tissues and body fluids obtained from 20 autopsy cases were analyzed. The levels of 25 PBDE congeners, ranging from tri- to hexa-BDEs, were assessed. The geometric means of the sum of the concentrations of PBDE congeners having detection frequencies >50 % (ΣPBDE) in the blood, liver, bile, and adipose tissue were 2.4, 2.6, 1.4, and 4.3 ng/g lipid, respectively. The most abundant congeners were BDE-47 and BDE-153, followed by BDE-100, BDE-99, and BDE-28+33. These concentrations of PBDE congeners were similar to other reports of human exposure in Japan but were notably lower than concentrations than those reported in the USA. Significant positive correlations were observed between the concentrations of predominant congeners and ΣPBDE among the samples analyzed. The ΣPBDE concentration was highest in the adipose tissue, but PBDEs were distributed widely among the tissues and body fluids analyzed. The PBDE levels observed in the present study are similar to those reported in previous studies in Japan and significantly lower than those reported in the USA.

Cytoskeletal proteins in the cerebrospinal fluid as biomarker of multiple sclerosis.

Science.gov (United States)

Madeddu, Roberto; Farace, Cristiano; Tolu, Paola; Solinas, Giuliana; Asara, Yolande; Sotgiu, Maria Alessandra; Delogu, Lucia Gemma; Prados, Jose Carlos; Sotgiu, Stefano; Montella, Andrea

2013-02-01

The axonal cytoskeleton is a finely organized system, essential for maintaining the integrity of the axon. Axonal degeneration is implicated in the pathogenesis of unremitting disability of multiple sclerosis (MS). Purpose of this study is to evaluate levels of cytoskeletal proteins such as neurofilament light protein (NFL), glial fibrillary acidic protein (GFAP), and β-tubulin (β-Tub) isoforms II and III in the cerebrospinal fluid (CSF) of MS patients and their correlation with MS clinical indices. CSF levels of cytoskeletal proteins were determined in 51 patients: 33 with MS and 18 with other neurological diseases (OND). NFL, GFAP and β-Tub II proteins were significantly higher (p 0.05) was found between MS and OND with regard to β-Tub III. Interestingly, levels of β-Tub III and NFL were higher in progressive than in remitting MS forms; on the contrary, higher levels of β-Tub II and GFAP were found in remitting MS forms. However, with the exception of β-Tub III, all proteins tend to decrease their CSF levels concomitantly with the increasing disability (EDSS) score. Overall, our results might indicate β-Tub II as a potential candidate for diagnostic and β-Tub III as a possible prognostic biomarker of MS. Therefore, further analyses are legitimated and desirable.

Cholera toxin can catalyze ADP-ribosylation of cytoskeletal proteins

International Nuclear Information System (INIS)

Kaslow, H.R.; Groppi, V.E.; Abood, M.E.; Bourne, H.R.

1981-01-01

Cholera toxin catalyzes transfer of radiolabel from [ 32 P]NAD + to several peptides in particulate preparations of human foreskin fibroblasts. Resolution of these peptides by two-dimensional gel electrophoresis allowed identification of two peptides of M/sub r/ = 42,000 and 52,000 as peptide subunits of a regulatory component of adenylate cyclase. The radiolabeling of another group of peptides (M/sub r/ = 50,000 to 65,000) suggested that cholera toxin could catalyze ADP-ribosylation of cytoskeletal proteins. This suggestion was confirmed by showing that incubation with cholera toxin and [ 32 P]NAD + caused radiolabeling of purified microtubule and intermediate filament proteins

Polybrominated diphenyl ethers in airborne particulates collected during a research expedition from the Bohai Sea to the Arctic.

Science.gov (United States)

Wang, Xin-Ming; Ding, Xiang; Mai, Bi-Xian; Xie, Zhou-Qing; Xiang, Cai-Hong; Sun, Li-Guang; Sheng, Guo-Ying; Fu, Jia-Mo; Zeng, Eddy Y

2005-10-15

In July to September 2003, particulates in the oceanic atmosphere from the Bohai Sea to the high Arctic (37 degrees N to 80 degrees N) were collected aboard a research expedition icebreaker, Xuelong (Snow Dragon), under the 2003 Chinese Arctic Research Expedition Program (CHINARE 2003). These samples were analyzed to elucidate the atmospheric distributions of polybrominated diphenyl ethers (PBDEs) in the North Pacific Ocean and adjacent Arctic region. The levels of 11 PBDE congeners (BDE-28, -47, -66, -100, -99, -85, -154, -153, -138, -183, and -209; the sum was defined as sigma11PBDE) in the oceanic atmosphere of Far East Asia (34-48 degrees N/122-148 degrees E) ranged from 2.25 to 198.9 pg/m3 with a mean of 58.3 pg/m3. BDE-47, -99, -100, and -209 were the dominant congeners in all the samples, suggesting that the widely used commercial penta- and deca-BDE products were the original sources. The PBDE levels exhibited a decreasing trend from the mid- to high-latitudinal regions of the North Pacific Ocean, probably resulting from dilution, deposition, and decomposition of PBDEs during long-range transport of air masses. On the other hand, no apparent geographical pattern of PBDE distribution was observed within the Arctic, attributable to unstable air circulation and strong air mixing. Correlations among the PBDE congeners suggested that air masses collected from the North Pacific Ocean were relatively fresh, whereas those from the Arctic were aged as a result of photodecompoisiton. The higher average level (17.3 pg/m3) of PBDE congeners in the Arctic than those in the adjacent North Pacific Ocean (12.8 pg/m3) or other remote areas reported in the literature was attributed to the impact of the North American continent and temperature effects, which was consistent with the hypotheses of global fractionation.

Technetium-99 levels in pertechnetate solutions from (n,γ) and (n,f) molybdenum-99 generators

International Nuclear Information System (INIS)

Moore, P.W.

1983-04-01

There is increasing evidence that, in some radiopharmaceutical kits, Tc-99 has an adverse effect on the imaging and labelling performance of Tc-99m. For example, labelling efficiency with red blood cells can be affected when 99/99m ratios exceed about 4:1. The 99/99m ratio in a target is about 13.5:1 after a seven-day irradiation in a nuclear reactor. The ratio increases slightly during the time needed for processing. With the chromatographic generators used in hospitals, up to 90 hours may elapse between the final wash stage of manufacture and the first elution, during which time, 99/99m ratios can increase to about 90:1. If elution efficiencies are high and the time between elutions is between 12 and 24 hours, ratios in the generator, hence in the eluates, may actually increase with each elution. In the case of ready-to-inject pertechnetate solutions, the critical time at which 99/99m ratios increase rapidly is the time between elution and use. If production conditions are poor, ratios may increase to more than 600:1 by the time of use. With better conditions and production schedules Tc-99 levels at the time of use are comparable to those from chromatographic generators

Estimation of Anaerobic Debromination Rate Constants of PBDE Pathways Using an Anaerobic Dehalogenation Model.

Science.gov (United States)

Karakas, Filiz; Imamoglu, Ipek

2017-04-01

This study aims to estimate anaerobic debromination rate constants (k m ) of PBDE pathways using previously reported laboratory soil data. k m values of pathways are estimated by modifying a previously developed model as Anaerobic Dehalogenation Model. Debromination activities published in the literature in terms of bromine substitutions as well as specific microorganisms and their combinations are used for identification of pathways. The range of estimated k m values is between 0.0003 and 0.0241 d -1 . The median and maximum of k m values are found to be comparable to the few available biologically confirmed rate constants published in the literature. The estimated k m values can be used as input to numerical fate and transport models for a better and more detailed investigation of the fate of individual PBDEs in contaminated sediments. Various remediation scenarios such as monitored natural attenuation or bioremediation with bioaugmentation can be handled in a more quantitative manner with the help of k m estimated in this study.

Modulators of cytoskeletal reorganization in CA1 hippocampal neurons show increased expression in patients at mid-stage Alzheimer's disease.

Directory of Open Access Journals (Sweden)

Patricia F Kao

2010-10-01

Full Text Available During the progression of Alzheimer's disease (AD, hippocampal neurons undergo cytoskeletal reorganization, resulting in degenerative as well as regenerative changes. As neurofibrillary tangles form and dystrophic neurites appear, sprouting neuronal processes with growth cones emerge. Actin and tubulin are indispensable for normal neurite development and regenerative responses to injury and neurodegenerative stimuli. We have previously shown that actin capping protein beta2 subunit, Capzb2, binds tubulin and, in the presence of tau, affects microtubule polymerization necessary for neurite outgrowth and normal growth cone morphology. Accordingly, Capzb2 silencing in hippocampal neurons resulted in short, dystrophic neurites, seen in neurodegenerative diseases including AD. Here we demonstrate the statistically significant increase in the Capzb2 expression in the postmortem hippocampi in persons at mid-stage, Braak and Braak stage (BB III-IV, non-familial AD in comparison to controls. The dynamics of Capzb2 expression in progressive AD stages cannot be attributed to reactive astrocytosis. Moreover, the increased expression of Capzb2 mRNA in CA1 pyramidal neurons in AD BB III-IV is accompanied by an increased mRNA expression of brain derived neurotrophic factor (BDNF receptor tyrosine kinase B (TrkB, mediator of synaptic plasticity in hippocampal neurons. Thus, the up-regulation of Capzb2 and TrkB may reflect cytoskeletal reorganization and/or regenerative response occurring in hippocampal CA1 neurons at a specific stage of AD progression.

Presence of polybrominated diphenyl ethers in Spanish sewage sludges. Important contribution of deca-BDE

Energy Technology Data Exchange (ETDEWEB)

Fabrellas, B.; Larrazabal, D.; Martinez, M.A. [CIEMAT, Madrid (Spain); Eljarrat, E.; Barcelo, D. [I.I.Q.A.B., C.S.I.C, Barcelona (Spain)

2004-09-15

Introduction Polybrominated diphenyl ethers (PBDE) are a family of synthetic chemicals widely used in industry to delay, inhibit or even suppress combustion process in manufactured items. Flame retardant products are frequently added into plastic, electronic, paint and textile materials to reduce the risk of ignition. During last years, increasing levels of PBDE have been detected in the environment, suggesting release from the treated surface as main pathway for environmental intake. Their physicochemical structure make them substances of highly lypophylic, bioaccumulative and persistent nature, with potential toxic effects observed onto wildlife and humans. Some European countries (Switzerland and Sweden) have promoted strategies to enlarge the knowledge of PBDE, in particular their occurrence and levels on sewage sludge. Observations point domestic washing of garment/clothes and industrial discharges from plastic and textile manufacture industry as major sources of contamination. First European results from 1988 revealed levels of about 20-30 {mu}g/kg dw of PBDEs (BDEs 47, 99 and 100) in sludge samples collected in Sweden. More recently, another Swedish survey conducted on three waste-water treatment facilities pointed levels of PBDE (BDE 47, 99 and 209) of about 200 ng/g dw, along with minor contribution of other contaminants such as TBBPA and HBCD iv. Few studies have been carried out in US. Hale et al. compared levels of Tetra-, PentaBDE (BDE 47, BDE 99 and BDE 100) and DecaBDE 209 congeners in sludge from different US locations. Values ranged from 1000 to 2290 {mu}g/kg dw (Tri- to HexaBDE) and from 84 to 4890 {mu}g/kg dw for DecaBDE 209, with mean values of about 1600 and 1000 {mu}g/kg dw, respectively. In general, concentrations of BDE 47, 99, 100 and 209 exceeded those of the major PCB congeners and other halogenated contaminants also found in the sludge. Following this trend, this work aims a preliminary assessment of selected PBDE congener levels on

Using Force to Probe Single-Molecule Receptor-Cytoskeletal Anchoring Beneath the Surface of a Living Cell

DEFF Research Database (Denmark)

Evans, Evan; Kinoshita, Koji

2007-01-01

-cytoskeletal unbinding increased exponentially with the level of force, suggesting disruption at a site of single-molecule interaction. Since many important enzymes and signaling molecules are closely associated with a membrane receptor-cytoskeletal linkage, pulling on a receptor could alter interactions among its......The ligation of cell surface receptors often communicates a signal that initiates a cytoplasmic chemical cascade to implement an important cell function. Less well understood is how physical stress applied to a cell surface adhesive bond propagates throughout the cytostructure to catalyze...... or trigger important steps in these chemical processes. Probing the nanoscale impact of pulling on cell surface bonds, we discovered that receptors frequently detach prematurely from the interior cytostructure prior to failure of the exterior adhesive bond [Evans, E., Heinrich, V., Leung, A., and Kinoshita...

Performance tests on new chromatographic material for 99Mo-99mTc generators

International Nuclear Information System (INIS)

Sombrito, Elvira Z.; Bulos, Adelina D.M.

2004-01-01

all three batches although PZC020522 showed the presence of a small amount of crystalline structure in the sample. X-ray fluorescence analysis gave about 40% zirconium in the sample. These results need to be compared with the results of tests obtained at higher activity of molybdenum-99 to determine any radiation effect that may affect the elution behavior of the column material. The rate of decomposition of the gel, which is affecting its performance characteristics, needs to be defined. (author)

Role of cyclic nucleotide-dependent actin cytoskeletal dynamics:Ca(2+](i and force suppression in forskolin-pretreated porcine coronary arteries.

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Kyle M Hocking

Full Text Available Initiation of force generation during vascular smooth muscle contraction involves a rise in intracellular calcium ([Ca(2+]i and phosphorylation of myosin light chains (MLC. However, reversal of these two processes alone does not account for the force inhibition that occurs during relaxation or inhibition of contraction, implicating that other mechanisms, such as actin cytoskeletal rearrangement, play a role in the suppression of force. In this study, we hypothesize that forskolin-induced force suppression is dependent upon changes in actin cytoskeletal dynamics. To focus on the actin cytoskeletal changes, a physiological model was developed in which forskolin treatment of intact porcine coronary arteries (PCA prior to treatment with a contractile agonist resulted in complete suppression of force. Pretreatment of PCA with forskolin suppressed histamine-induced force generation but did not abolish [Ca(2+]i rise or MLC phosphorylation. Additionally, forskolin pretreatment reduced filamentous actin in histamine-treated tissues, and prevented histamine-induced changes in the phosphorylation of the actin-regulatory proteins HSP20, VASP, cofilin, and paxillin. Taken together, these results suggest that forskolin-induced complete force suppression is dependent upon the actin cytoskeletal regulation initiated by the phosphorylation changes of the actin regulatory proteins and not on the MLC dephosphorylation. This model of complete force suppression can be employed to further elucidate the mechanisms responsible for smooth muscle tone, and may offer cues to pathological situations, such as hypertension and vasospasm.

Mismatched uptake of Tc-99m-ECD and Tc-99m-HMPAO in subacute cerebral infarction: Tc-99m-ECD for viability and Tc-99m-HMPAO for flow restoration

Energy Technology Data Exchange (ETDEWEB)

Lee, D. S.; Hyun, I. Y.; Kim, S. K. [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)] [and others

1997-07-01

Tc-99m-HMPAO reflects tissue perfusion but Tc-99m-ECD uptake is affected by tissue viability in addition to tissue perfusion which the varied state of cellular retention of Tc-99m-ECD reflects. Luxuriously perfused area on Tc-99m-HMPAO SPECT implies that this cortex was already reperfused either spontaneously or after thrombolysis and that accompanied paralysis of vascular reactivity in those zones warms progressive deterioration. We tried to find out if we can use sequential Tc-99m-ECD/Tc-99m-HMPAO SPECT to reveal cortical perfusion and severity and range of risky areas of cerbral cortex despite reperfusion in sub-acute infarction. In 13 patients (M ; F =7 : 6, mean age 57 (range: 26-84)) with cortical (n=12) and basal ganglia infarction (1), we performed sequential Tc-99m-ECD/Tc-99m-HMPAO SPECT at the same position. At first, 555 MBq of Tc-99m-ECD was injected and imaged and then 1110 MBq of Tc-99m-HMPAO was injected again and imaged with the patients in situ, and the first image (Tc-99m-ECD) and the subtracted image (2nd- 1st : Tc-99m-HMPAO) were compared slice by slice. Study was done from 3 days to 31 days (16{+-}9) after ictus. Tc-99m-ECD uptake was always less than or equal to Tc-99m-HMPAO uptake at the lesion in all cases. Luxury perfusion was prominent in four patients. Mismatched uptake was found in 10 patients. Severity of mismatch showed diverse spectrum and was ranged from total middle cerebral artery territory (1 case) to peripheral thin zones around infarction (2 cases). The other 7 showed intermediate amount of tissues with mismatch , i.e., Tc-99m-ECD defects where Tc-99m-HMPAO uptake is in part increased, normal or decreased. Upon discharge, patients having more uptake with Tc-99m-ECD predicted improvement. Patients having mismatched uptake went dichotomous way. In conclusion, Tc-99m-ECD/Tc-99m-HMPAO sequential SPECT is feasible and reveal both tissue perfusion (Tc-99m-HMPAO ) and discrepant Tc-99m-ECD uptake probably reflecting viability in acute

Kynurenic Acid Prevents Cytoskeletal Disorganization Induced by Quinolinic Acid in Mixed Cultures of Rat Striatum.

Science.gov (United States)

Pierozan, Paula; Biasibetti-Brendler, Helena; Schmitz, Felipe; Ferreira, Fernanda; Pessoa-Pureur, Regina; Wyse, Angela T S

2018-06-01

Kynurenic acid (KYNA) is a neuroactive metabolite of tryptophan known to modulate a number of mechanisms involved in neural dysfunction. Although its activity in the brain has been widely studied, the effect of KYNA counteracting the actions of quinolinic acid (QUIN) remains unknown. The present study aims at describing the ability of 100 μM KYNA preventing cytoskeletal disruption provoked by QUIN in astrocyte/neuron/microglia mixed culture. KYNA totally preserved cytoskeletal organization, cell morphology, and redox imbalance in mixed cultures exposed to QUIN. However, KYNA partially prevented morphological alteration in isolated primary astrocytes and failed to protect the morphological alterations of neurons caused by QUIN exposure. Moreover, KYNA prevented QUIN-induced microglial activation and upregulation of ionized calcium-binding adapter molecule 1 (Iba-1) and partially preserved tumor necrosis factor-α (TNF-α) level in mixed cultures. TNF-α level was also partially preserved in astrocytes. In addition to the mechanisms dependent on redox imbalance and microglial activation, KYNA prevented downregulation of connexin-43 and the loss of functionality of gap junctions (GJs), preserving cell-cell contact, cytoskeletal organization, and cell morphology in QUIN-treated cells. Furthermore, the toxicity of QUIN targeting the cytoskeleton of mixed cultures was not prevented by the N-methyl-D-aspartate (NMDA) antagonist MK-801. We suggest that KYNA protects the integrity of the cytoskeleton of mixed cultures by complex mechanisms including modulating microglial activation preventing oxidative imbalance and misregulated GJs leading to disrupted cytoskeleton in QUIN-treated cells. This study contributed to elucidate the molecular basis of KYNA protection against QUIN toxicity.

Parathyroid hormone promotes the disassembly of cytoskeletal actin and myosin in cultured osteoblastic cells: Mediation by cyclic AMP

International Nuclear Information System (INIS)

Egan, J.J.; Gronowicz, G.; Rodan, G.A.

1991-01-01

Parathyroid hormone (PTH) alters the shape of osteoblastic cells both in vivo and in vitro. In this study, we examined the effect of PTH on cytoskeletal actin and myosin, estimated by polyacrylamide gel electrophoresis of Triton X-100 (1%) nonextractable proteins. After 2-5 minutes, PTH caused a rapid and transient decrease of 50-60% in polymerized actin and myosin associated with the Triton X-100 nonextractable cytoskeleton. Polymerized actin returned to control levels by 30 min. The PTH effect was dose-dependent with an IC50 of about 1 nM, and was partially inhibited by the (3-34) PTH antagonist. PTH caused a rapid transient rise in cyclic AMP (cAMP) in these cells that peaked at 4 min, while the nadir in cytoskeletal actin and myosin was recorded around 5 min. The intracellular calcium chelator Quin-2/AM (10 microM) also decreased cytoskeletal actin and myosin, to the same extent as did PTH (100 nM). To distinguish between cAMP elevation and Ca++ reduction as mediators of PTH action, we measured the phosphorylation of the 20 kD (PI 4.9) myosin light chain in cells preincubated with [32P]-orthophosphate. The phosphorylation of this protein decreased within 2-3 min after PTH addition and returned to control levels after 5 min. The calcium ionophore A-23187 did not antagonize this PTH effect. Visualization of microfilaments with rhodamine-conjugated phalloidin showed that PTH altered the cytoskeleton by decreasing the number of stress fibers. These changes in the cytoskeleton paralleled changes in the shape of the cells from a spread configuration to a stellate form with retracting processes. The above findings indicate that the alteration in osteoblast shape produced by PTH involve relatively rapid and transient changes in cytoskeletal organization that appear to be mediated by cAMP

Cytoskeletal proteins in the follicular wall of normal andcystic ovaries of sows

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Fabiano J.F. de Sant'Ana

2015-02-01

Full Text Available The expression of cytoskeletal proteins was evaluated immunohistochemically in 36 normal ovaries sampled from 18 sows and 44 cystic ovaries sampled from of 22 sows, was evaluated. All sows had history of reproductive problems, such as infertility or subfertility. The immunohistochemically stained area (IHCSA was quantified through image analysis to evaluate the expression of these proteins in the follicular wall of secondary, tertiary, and cystic follicles. Cytokeratins (CK immunoreactivity was strong in the granulosa cell layer (GC and mild in the theca interna (TI and externa (TE of the normal follicles. There was severe reduction of the reaction to CK in the GC in the cystic follicles, mainly in the luteinized cysts. The immunoreactivity for vimentin was higher in the GC from normal and cystic follicles in contrast with the other follicular structures. In the luteinized cysts, the IHCSA for vimentin was significantly higher in TI and in both observed cysts, the labeling was more accentuated in TE. Immunohistochemical detection of desmin and α-SMA was restricted to the TE, without differences between the normal and cystic follicles. The results of the current study show that the development of ovarian cysts in sows is associated to changes in the expression of the cytoskeletal proteins CK and vimentin.

Reinforcement versus fluidization in cytoskeletal mechanoresponsiveness.

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Ramaswamy Krishnan

Full Text Available Every adherent eukaryotic cell exerts appreciable traction forces upon its substrate. Moreover, every resident cell within the heart, great vessels, bladder, gut or lung routinely experiences large periodic stretches. As an acute response to such stretches the cytoskeleton can stiffen, increase traction forces and reinforce, as reported by some, or can soften and fluidize, as reported more recently by our laboratory, but in any given circumstance it remains unknown which response might prevail or why. Using a novel nanotechnology, we show here that in loading conditions expected in most physiological circumstances the localized reinforcement response fails to scale up to the level of homogeneous cell stretch; fluidization trumps reinforcement. Whereas the reinforcement response is known to be mediated by upstream mechanosensing and downstream signaling, results presented here show the fluidization response to be altogether novel: it is a direct physical effect of mechanical force acting upon a structural lattice that is soft and fragile. Cytoskeletal softness and fragility, we argue, is consistent with early evolutionary adaptations of the eukaryotic cell to material properties of a soft inert microenvironment.

Cytoskeletal proteins from human skin fibroblasts, peripheral blood leukocytes, and a lymphoblastoid cell line compared by two-dimensional gel electrophoresis

International Nuclear Information System (INIS)

Giometti, C.S.; Willard, K.E.; Anderson, N.L.

1982-01-01

Differences in proteins between cells grown as suspension cultures and those grown as attached cultures were studied by comparing the proteins of detergent-resistant cytoskeletons prepared from peripheral blood leukocytes and a lymphoblastoid cell line (GM607) (both grown as suspension cultures) and those of human skin fibroblasts (grown as attached cultures) by two-dimensional gel electrophoresis. The major cytoskeletal proteins of the leukocytes were also present in the protein pattern of GM607 cytoskeletons. In contrast, the fibroblast cytoskeletal protein pattern contained four groups of proteins that differed from the patterns of the leukocytes and GM607. In addition, surface labeling of GM607 and human fibroblasts with 125 I demonstrated that substantial amounts of vimentin and actin are exposed at the surface of the attached fibroblasts, but there is little evidence of similar exposure at the surface of the suspension-grown GM607. These results demonstrate some differences in cytoskeletal protein composition between different types of cells could be related to their ability or lack of ability to grow as attached cells in tissue culture

Congener distribution of polybrominated diphenyl ethers in feral carp (Cyprinus carpio) from the Llobregat River, Spain

Energy Technology Data Exchange (ETDEWEB)

Labandeira, Ana [Department of Environmental Chemistry, IIQAB, CSIC, Jordi Girona 18-26, 08034 Barcelona (Spain); Eljarrat, Ethel [Department of Environmental Chemistry, IIQAB, CSIC, Jordi Girona 18-26, 08034 Barcelona (Spain)]. E-mail: eeeqam@cid.csic.es; Barcelo, Damia [Department of Environmental Chemistry, IIQAB, CSIC, Jordi Girona 18-26, 08034 Barcelona (Spain)

2007-03-15

Feral carp were collected at two Spanish rivers, Anoia and Cardener, showing PBDE levels from 29 to 638 ng/g lipid weight (lw) and from 54 to 744 ng/g lw, respectively. Sediments were also collected, showing PBDE contamination between 2 and 10 ng/g dry weight (dw). Differences in PBDE profiles between sediments and fish were noticed. Contribution of BDE-47 in sediment was up to 11%, whereas it contributed 37-90% of PBDEs in fish. Similar results were observed for BDE-154, which was only detected in one sediment sample, but presented high contribution in carp. In contrast, BDE-99 contributed up to 32% in sediments, but it was not detected in fish. Similar results were observed for BDE-153, BDE-183 and BDE-209. The main reason for their concentration decrease or absence in biota may be due to low bioavailability potential or due to biotransformation processes. - Differences in PBDE profiles between sediments and fish were observed, suggesting biotransformation in carp.

Congener distribution of polybrominated diphenyl ethers in feral carp (Cyprinus carpio) from the Llobregat River, Spain

International Nuclear Information System (INIS)

Labandeira, Ana; Eljarrat, Ethel; Barcelo, Damia

2007-01-01

Feral carp were collected at two Spanish rivers, Anoia and Cardener, showing PBDE levels from 29 to 638 ng/g lipid weight (lw) and from 54 to 744 ng/g lw, respectively. Sediments were also collected, showing PBDE contamination between 2 and 10 ng/g dry weight (dw). Differences in PBDE profiles between sediments and fish were noticed. Contribution of BDE-47 in sediment was up to 11%, whereas it contributed 37-90% of PBDEs in fish. Similar results were observed for BDE-154, which was only detected in one sediment sample, but presented high contribution in carp. In contrast, BDE-99 contributed up to 32% in sediments, but it was not detected in fish. Similar results were observed for BDE-153, BDE-183 and BDE-209. The main reason for their concentration decrease or absence in biota may be due to low bioavailability potential or due to biotransformation processes. - Differences in PBDE profiles between sediments and fish were observed, suggesting biotransformation in carp

cAMP/PKA signalling reinforces the LATS–YAP pathway to fully suppress YAP in response to actin cytoskeletal changes

Science.gov (United States)

Kim, Minchul; Kim, Miju; Lee, Seunghee; Kuninaka, Shinji; Saya, Hideyuki; Lee, Ho; Lee, Sookyung; Lim, Dae-Sik

2013-01-01

Actin cytoskeletal damage induces inactivation of the oncoprotein YAP (Yes-associated protein). It is known that the serine/threonine kinase LATS (large tumour suppressor) inactivates YAP by phosphorylating its Ser127 and Ser381 residues. However, the events downstream of actin cytoskeletal changes that are involved in the regulation of the LATS–YAP pathway and the mechanism by which LATS differentially phosphorylates YAP on Ser127 and Ser381 in vivo have remained elusive. Here, we show that cyclic AMP (cAMP)-dependent protein kinase (PKA) phosphorylates LATS and thereby enhances its activity sufficiently to phosphorylate YAP on Ser381. We also found that PKA activity is involved in all contexts previously reported to trigger the LATS–YAP pathway, including actin cytoskeletal damage, G-protein-coupled receptor activation, and engagement of the Hippo pathway. Inhibition of PKA and overexpression of YAP cooperate to transform normal cells and amplify neural progenitor pools in developing chick embryos. We also implicate neurofibromin 2 as an AKAP (A-kinase-anchoring protein) scaffold protein that facilitates the function of the cAMP/PKA–LATS–YAP pathway. Our study thus incorporates PKA as novel component of the Hippo pathway. PMID:23644383

Brominated flame retardants in Canadian chicken egg yolks.

Science.gov (United States)

Rawn, D F K; Sadler, A; Quade, S C; Sun, W-F; Lau, B P-Y; Kosarac, I; Hayward, S; Ryan, J J

2011-06-01

Chicken eggs categorised as conventional, omega-3 enriched, free range and organic were collected at grading stations in three regions of Canada between 2005 and 2006. Free run eggs, which were only available for collection from two regions, were also sampled during this time frame. Egg yolks from each of these egg types (n = 162) were analysed to determine brominated flame retardant levels, specifically polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCD). PBDEs were detected in 100% of the 162 samples tested, while HBCD was observed in 85% of the egg yolks. Total PBDE concentrations in egg yolks ranged from 0.018 to 20.9 ng g(-1) lipid (median = 3.03 ng g(-1) lipid), with PBDE 209 identified as being the major contributor to ΣPBDE concentrations. In addition to PBDE 209, PBDE 99, 47, 100, 183 and 153 were important contributors to ΣPBDE concentrations. Total HBCD concentrations ranged from below the limit of detection to a maximum concentration of 71.9 ng g(-1) lipid (median = 0.053 ng g(-1) lipid). The α-isomer was the dominant contributor to ΣHBCD levels in Canadian egg yolks and was the most frequently detected HBCD isomer. ΣPBDE levels exhibited large differences in variability between combinations of region and type. ΣHBCD concentrations were not significantly different among regions, although differences were observed between the different types of egg yolks analysed in the present study.

Intracellular Transport of Cargo in a Sub-diffusive Environment over an Explicit Cytoskeletal Network

Science.gov (United States)

Maelfeyt, Bryan; Gopinathan, Ajay

Intracellular transport occurs in nearly all eukaryotic cells, where materials such as proteins, lipids, carbohydrates, and nucleic acids travel to target locations through phases of passive, diffusion-based transport and active, motor-driven transport along filaments that make up the cell's cytoskeleton.We develop a computational model of the process with explicit cytoskeletal filament networks. In the active transport phase, cargo moves in straight lines along these filaments that are spread throughout the cell. To model the passive transport phase of cargo in the cytoplasm, where anomalous sub-diffusion is thought to take place, we implement a continuous-time random walk. We use this approach to provide a stepping stone to a predictive model where we can determine transport properties over a cytoskeletal network provided by experimental images of real filaments. We illustrate our approach by modeling the transport of insulin out of the cell and determining the impact of network geometry, anomalous sub-diffusion and motor number on the first-passage time distributions for insulin granules reaching their target destinations on the membrane.

Comparison of sup(99m)Tc-MDP to sup(99m)Tc-pertechnetate by computerized quantitative joint scintigraphy

International Nuclear Information System (INIS)

Rekonen, A.; Moettoenen, T.; Oka, M.

1982-01-01

99mTc-pertechnetate was compared to 99mTc-MDP in joint pairs with asymmetric arthritis. Markedly elevated joint activity ratios (inflamed/uninflamed joint) were measured in all the joint pairs studied. In the joints affected by reactive arthritis and without roentgenologic changes the mean joint activity was the same with both tracers. A very high activity ratio with 99mTc-MDP was found in septic arthritis. In rheumatoid arthritis the sensitivity of 99mTc-MDP as an indicator of active arthritis seemed to be better than that of 99mTc-pertechnetate. Even in joints without erosions in roentgenograms the joint activity ratios were markedly elevated with 99mTc-MDP. This suggests, that high activity in 99mTc-MDP scanning might be prognostic of erosive joint changes. In this work a profile curve was used for quantitation differences between joints

Cytoskeletal protein translation and expression in the rat brain are stressor-dependent and region-specific.

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Petra Sántha

Full Text Available Stress is an integral component of life that can sometimes cause a critical overload, depending on the qualitative and quantitative natures of the stressors. The involvement of actin, the predominant component of dendritic integrity, is a plausible candidate factor in stress-induced neuronal cytoskeletal changes. The major aim of this study was to compare the effects of three different stress conditions on the transcription and translation of actin-related cytoskeletal genes in the rat brain. Male Wistar rats were exposed to one or other of the frequently used models of physical stress, i.e. electric foot shock stress (EFSS, forced swimming stress (FSS, or psychosocial stress (PSS for periods of 3, 7, 14, or 21 days. The relative mRNA and protein expressions of β-actin, cofilin and mitogen-activated protein kinase 1 (MAPK-1 were determined by qRT- PCR and western blotting from hippocampus and frontal cortex samples. Stressor-specific alterations in both β-actin and cofilin expression levels were seen after stress. These alterations were most pronounced in response to EFSS, and exhibited a U-shaped time course. FSS led to a significant β-actin mRNA expression elevation in the hippocampus and the frontal cortex after 3 and 7 days, respectively, without any subsequent change. PSS did not cause any change in β-actin or cofilin mRNA or protein expression in the examined brain regions. EFSS, FSS and PSS had no effect on the expression of MAPK-1 mRNA at any tested time point. These findings indicate a very delicate, stress type-dependent regulation of neuronal cytoskeletal components in the rat hippocampus and frontal cortex.

Evaluation of highly loaded low specific activity 99Mo on alumina column as 99mTc generator

International Nuclear Information System (INIS)

Asif, M.; Mushtaq, A.

2010-01-01

Adsorption behavior of molybdate on acidic alumina was studied at boiling water bath temperature (∼100 deg C). Various parameters affecting the adsorption of molybdenum, such as pH, amount of molybdenum, incubation period, etc., were determined. A 99m Tc generator was prepared by adsorbing low specific activity 99 Mo (150 mg) on 1 g alumina. Elutions were carried out with saline. Performance of the generator such as 99 Mo breakthrough, aluminum contents, pH, elution profile, radiochemical purity, and labeling efficiency of kits were checked. (author)

Sex difference in polybrominated diphenyl ether concentrations of walleyes

Science.gov (United States)

Madenjian, Charles P.; Trombka, Autumn W.; Rediske, Richard R.; Jude, David J.; O'Keefe, James P.

2012-01-01

Polybrominated diphenyl ether (PBDE) concentrations were determined for mature male and mature female walleyes (Sander vitreus) sampled from the Saginaw Bay population during 2007. PBDE concentrations in prey fish caught in the Saginaw River, the primary tributary to Saginaw Bay, and in Saginaw Bay during 2005 and 2007 also were determined. Mature male and mature female walleyes averaged 70.3 ng/g and 24.8 ng/g, respectively, in ΣPBDE, which was equal to the sum of concentrations of six PBDE congeners (BDE-28, BDE-47, BDE-99, BDE-100, BDE-153, and BDE-154). This sex difference was likely due to males spending more time in the Saginaw River system than females. Prey fish captured in the Saginaw River were roughly ten times higher in ΣPBDE than those caught in Saginaw Bay. BDE-47 was the predominant congener in both walleyes and prey fish, and this congener contributed about 50%, on average, to ΣPBDE. Congener profiles differed significantly between the two sexes of walleyes. In contrast, congener profiles of the prey fish did not differ significantly between the river-caught fish and the bay-caught fish. One plausible explanation for these congener profile results was that net trophic transfer efficiencies of PBDEs to walleyes from their prey were similar for all congeners except BDE-28, and that diet composition differed between the two sexes of walleyes.

Fragility of foot process morphology in kidney podocytes arises from chaotic spatial propagation of cytoskeletal instability.

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Cibele V Falkenberg

2017-03-01

Full Text Available Kidney podocytes' function depends on fingerlike projections (foot processes that interdigitate with those from neighboring cells to form the glomerular filtration barrier. The integrity of the barrier depends on spatial control of dynamics of actin cytoskeleton in the foot processes. We determined how imbalances in regulation of actin cytoskeletal dynamics could result in pathological morphology. We obtained 3-D electron microscopy images of podocytes and used quantitative features to build dynamical models to investigate how regulation of actin dynamics within foot processes controls local morphology. We find that imbalances in regulation of actin bundling lead to chaotic spatial patterns that could impair the foot process morphology. Simulation results are consistent with experimental observations for cytoskeletal reconfiguration through dysregulated RhoA or Rac1, and they predict compensatory mechanisms for biochemical stability. We conclude that podocyte morphology, optimized for filtration, is intrinsically fragile, whereby local transient biochemical imbalances may lead to permanent morphological changes associated with pathophysiology.

Pulmonary clearance of 99mTc-DTPA and 99mTc-albumin in rabbits with surfactant dysfunction and lung injury

International Nuclear Information System (INIS)

Nilsson, K.; Wollmer, P.

1992-01-01

We measured the pulmonary clearance of inhaled 99m Tc-DTPA and 99m Tc-albumin in rabbits with surfacant dysfunction induced by dioctyl sodium sulphosuccinate and in rabbits with lung injury induced by oleic acid. After inhalation of 99m Tc-albumin in ten animals, clearance of the tracer from the lungs was monitored for 90 min. The first 30 min was a control period. Dioctyl sodium sulphosuccinate was then administered in aerosol and after another 30 min oleic acid was injected intravenously. Ten other rabbits were given 99m Tc-DTPA, and clearance was externally recorded for 60 min. Five animals inhaled detergent aerosol and five animals were given oleic acid intravenously after 30 min. Airway pressures, tidal volume, and arterial blood gases were measured before and after each intervention. The half-life of 99m Tc-albumin in the lung was 442 ± 123 min during the control period, 363 ± 52 min after detergent administration, and 134 ± 18 min after oleic acid administration. The half-life of 99m Tc-DTPA was 94 ± 16 min before and 10 ± 0.6 min after detergent administration and 75 ± 12 min before and 18 ± 1.8 min after oleic acid administration. Gas exchange was not affected by administration of dioctyl sodium sulphosuccinate but markedly impaired after injection of oleic acid. Compliance of the respiratory system remained unaffected by detergent but decreased after injection of oleic acid. The results indicate that the rate limiting factors for the alveolo-capillary transfer of 99m Tc-albumin and 99m Tc-DTPA are different. Surfactant dysfunction affects the transfer of 99m Tc-DTPA but not 99m Tc-albumin. (author)

Levels and congener profiles of polybrominated diphenyl ethers (PBDEs) in Zebra mussels (D. polymorpha) from Lake Maggiore (Italy)

Energy Technology Data Exchange (ETDEWEB)

Binelli, A. [Department of Biology, Via Celoria 26, University of Milan, 20133 Milan (Italy)], E-mail: andrea.binelli@unimi.it; Guzzella, L.; Roscioli, C. [IRSA-CNR, 20047 Brugherio (Milan) (Italy)

2008-06-15

Several congeners of polybrominated diphenyl ethers (PBDEs) were monitored in 14 different sampling stations of Lake Maggiore, the second largest Italian lake in regard to surface, volume and average depth, using the sentinel-organism Zebra mussel (Dreissena polymorpha). Results revealed a moderate contamination with {sigma}PBDE levels (BDE-17, -28, -47, -66, -71, -85, -99, -100, -138, -153, -154, -183, -190 and -209) ranging from 40 to 447 ng g{sup -1} lipid weight which are similar to those found in environments polluted by deposition or atmospheric transport. The general order of decreasing congener contribution to the total load was BDE-47 > -99 > -100 > -209, which closely reflected patterns observed in mussels collected in freshwater ecosystems worldwide. - This study shows the first data of PBDE contamination in freshwater invertebrates from Mediterranean basin.

Levels and congener profiles of polybrominated diphenyl ethers (PBDEs) in Zebra mussels (D. polymorpha) from Lake Maggiore (Italy)

International Nuclear Information System (INIS)

Binelli, A.; Guzzella, L.; Roscioli, C.

2008-01-01

Several congeners of polybrominated diphenyl ethers (PBDEs) were monitored in 14 different sampling stations of Lake Maggiore, the second largest Italian lake in regard to surface, volume and average depth, using the sentinel-organism Zebra mussel (Dreissena polymorpha). Results revealed a moderate contamination with ΣPBDE levels (BDE-17, -28, -47, -66, -71, -85, -99, -100, -138, -153, -154, -183, -190 and -209) ranging from 40 to 447 ng g -1 lipid weight which are similar to those found in environments polluted by deposition or atmospheric transport. The general order of decreasing congener contribution to the total load was BDE-47 > -99 > -100 > -209, which closely reflected patterns observed in mussels collected in freshwater ecosystems worldwide. - This study shows the first data of PBDE contamination in freshwater invertebrates from Mediterranean basin

Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure

Science.gov (United States)

Maniotis, A. J.; Chen, C. S.; Ingber, D. E.

1997-01-01

We report here that living cells and nuclei are hard-wired such that a mechanical tug on cell surface receptors can immediately change the organization of molecular assemblies in the cytoplasm and nucleus. When integrins were pulled by micromanipulating bound microbeads or micropipettes, cytoskeletal filaments reoriented, nuclei distorted, and nucleoli redistributed along the axis of the applied tension field. These effects were specific for integrins, independent of cortical membrane distortion, and were mediated by direct linkages between the cytoskeleton and nucleus. Actin microfilaments mediated force transfer to the nucleus at low strain; however, tearing of the actin gel resulted with greater distortion. In contrast, intermediate filaments effectively mediated force transfer to the nucleus under both conditions. These filament systems also acted as molecular guy wires to mechanically stiffen the nucleus and anchor it in place, whereas microtubules acted to hold open the intermediate filament lattice and to stabilize the nucleus against lateral compression. Molecular connections between integrins, cytoskeletal filaments, and nuclear scaffolds may therefore provide a discrete path for mechanical signal transfer through cells as well as a mechanism for producing integrated changes in cell and nuclear structure in response to changes in extracellular matrix adhesivity or mechanics.

Evaluation of the toxic effects of brominated compounds (BDE-47, 99, 209, TBBPA) and bisphenol A (BPA) using a zebrafish liver cell line, ZFL

Energy Technology Data Exchange (ETDEWEB)

Yang, Jie; Chan, King Ming, E-mail: kingchan@cuhk.edu.hk

2015-02-15

Highlights: • A homologous zebrafish thyroid hormone (TH) receptor (TR) reporter gene system was developed in a zebrafish liver cell-line (ZFL) to study the possible effects of chemicals on TR activities. • BPA was found to have antagonistic effects on T3 induced TR activity, BDE-47, BDE-99, and TBBPA did not show any interference of TR activity. • Down regulation of deiodinases and some sulfation enzymes or phase II enzymes by the tested chemicals indicated their impacts on TH eleiminations. • The up-regulation of tranthyretin by BDE-47 at 96 h long-term exposure gave a link to the CYP family for its role in producing a more toxic and oxidized form. - Abstract: The toxic effects of three polybrominated diphenyl ether (PBDE) congeners (BDE-47, -99, and -209), tetrabromobisphenol A (TBBPA) and bisphenol A (BPA), were evaluated by determining their 24 h and 96 h median lethal concentrations using a zebrafish liver cell line, ZFL. It was found that BDE-47, BDE-99 and TBBPA showed comparative cytotoxicity within the range of 1.2–4.2 μM, and were more toxic than BPA (367.1 μM at 24 h and 357.6 μM at 96 h). However, BDE-209 induced only 15% lethality with exposures up to 25 μM. The molecular stresses of BDE-47, -99, TBBPA and BPA involved in thyroid hormone (TH) homeostasis and hepatic metabolism were also investigated. Using a reporter gene system to detect zebrafish thyroid hormone receptor β (zfTRβ) transcriptional activity, the median effective concentration of triiodothyronine (T3) was determined to be 9.2 × 10{sup −11} M. BDE-47, BDE-99, TBBPA and BPA alone, however, did not exhibit zfTRβ agonistic activity. BPA displayed T3 (0.1 nM) induced zfTRβ antagonistic activity with a median inhibitory concentration of 19.3 μM. BDE-47, BDE-99 and TBBPA displayed no antagonistic effects of T3-induced zfTRβ activity. Target gene expressions were also examined under acute exposures. The significant inhibition of different types of deiodinases by all of

Mycoplasma pneumoniae Cytoskeletal Protein HMW2 and the Architecture of the Terminal Organelle▿

OpenAIRE

Bose, Stephanie R.; Balish, Mitchell F.; Krause, Duncan C.

2009-01-01

The terminal organelle of Mycoplasma pneumoniae mediates cytadherence and gliding motility and functions in cell division. The defining feature of this complex membrane-bound cell extension is an electron-dense core of two segmented rods oriented longitudinally and enlarging to form a bulb at the distal end. While the components of the core have not been comprehensively identified, previous evidence suggested that the cytoskeletal protein HMW2 forms parallel bundles oriented lengthwise to yie...

14 CFR 99.19-99.31 - [Reserved

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false [Reserved] 99.19-99.31 Section 99.19-99.31 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR TRAFFIC AND GENERAL OPERATING RULES SECURITY CONTROL OF AIR TRAFFIC General §§ 99.19-99.31 [Reserved] ...

Oestradiol and progesterone differentially alter cytoskeletal protein expression and flame cell morphology in Taenia crassiceps.

Science.gov (United States)

Ambrosio, Javier R; Ostoa-Saloma, Pedro; Palacios-Arreola, M Isabel; Ruíz-Rosado, Azucena; Sánchez-Orellana, Pedro L; Reynoso-Ducoing, Olivia; Nava-Castro, Karen E; Martínez-Velázquez, Nancy; Escobedo, Galileo; Ibarra-Coronado, Elizabeth G; Valverde-Islas, Laura; Morales-Montor, Jorge

2014-09-01

We examined the effects of oestradiol (E2) and progesterone (P4) on cytoskeletal protein expression in the helminth Taenia crassiceps - specifically actin, tubulin and myosin. These proteins assemble into flame cells, which constitute the parasite excretory system. Total protein extracts were obtained from E2- and P4-treated T. crassiceps cysticerci and untreated controls, and analysed by one- and two-dimensional protein electrophoresis, flow cytometry, immunofluorescence and videomicroscopy. Exposure of T. crassiceps cysticerci to E2 and P4 induced differential protein expression patterns compared with untreated controls. Changes in actin, tubulin and myosin expression were confirmed by flow cytometry of parasite cells and immunofluorescence. In addition, parasite morphology was altered in response to E2 and P4 versus controls. Flame cells were primarily affected at the level of the ciliary tuft, in association with the changes in actin, tubulin and myosin. We conclude that oestradiol and progesterone act directly on T. crassiceps cysticerci, altering actin, tubulin and myosin expression and thus affecting the assembly and function of flame cells. Our results increase our understanding of several aspects of the molecular crosstalk between host and parasite, which might be useful in designing anthelmintic drugs that exclusively impair parasitic proteins which mediate cell signaling and pathogenic reproduction and establishment. Copyright © 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Identification of mechanosensitive genes during skeletal development: alteration of genes associated with cytoskeletal rearrangement and cell signalling pathways.

Science.gov (United States)

Rolfe, Rebecca A; Nowlan, Niamh C; Kenny, Elaine M; Cormican, Paul; Morris, Derek W; Prendergast, Patrick J; Kelly, Daniel; Murphy, Paula

2014-01-20

Mechanical stimulation is necessary for regulating correct formation of the skeleton. Here we test the hypothesis that mechanical stimulation of the embryonic skeletal system impacts expression levels of genes implicated in developmentally important signalling pathways in a genome wide approach. We use a mutant mouse model with altered mechanical stimulation due to the absence of limb skeletal muscle (Splotch-delayed) where muscle-less embryos show specific defects in skeletal elements including delayed ossification, changes in the size and shape of cartilage rudiments and joint fusion. We used Microarray and RNA sequencing analysis tools to identify differentially expressed genes between muscle-less and control embryonic (TS23) humerus tissue. We found that 680 independent genes were down-regulated and 452 genes up-regulated in humeri from muscle-less Spd embryos compared to littermate controls (at least 2-fold; corrected p-value ≤0.05). We analysed the resulting differentially expressed gene sets using Gene Ontology annotations to identify significant enrichment of genes associated with particular biological processes, showing that removal of mechanical stimuli from muscle contractions affected genes associated with development and differentiation, cytoskeletal architecture and cell signalling. Among cell signalling pathways, the most strongly disturbed was Wnt signalling, with 34 genes including 19 pathway target genes affected. Spatial gene expression analysis showed that both a Wnt ligand encoding gene (Wnt4) and a pathway antagonist (Sfrp2) are up-regulated specifically in the developing joint line, while the expression of a Wnt target gene, Cd44, is no longer detectable in muscle-less embryos. The identification of 84 genes associated with the cytoskeleton that are down-regulated in the absence of muscle indicates a number of candidate genes that are both mechanoresponsive and potentially involved in mechanotransduction, converting a mechanical stimulus

Developmental exposure to a brominated flame retardant: An assessment of effects on physiology, growth, and reproduction in a songbird, the zebra finch

International Nuclear Information System (INIS)

Eng, Margaret L.; Williams, Tony D.; Elliott, John E.

2013-01-01

Mixtures of polybrominated diphenyl ethers (PBDEs) have been widely used as additive flame retardants, and BDE-99 is one of the most predominant congeners found in the environment. BDE-99 has been reported in avian samples worldwide, yet knowledge of its toxicity to birds is minimal. We assessed the short- and long-term effects of nestling exposure to environmentally relevant levels of BDE-99 in a model passerine, the zebra finch. Early exposure to BDE-99 did not affect hematocrit, oxidative stress, or thyroid hormones in either the juvenile or adult stages, and there were no effects on chick growth or survival. BDE-99 exposure caused a dose-dependent delay in timing of reproduction, but there were no other effects on reproductive success. In zebra finches, endpoints related to reproductive behavior appear to be the most sensitive to BDE-99. However, passerines overall appear to be less sensitive than birds of prey or mammals to PBDE exposure. -- Highlights: •We exposed zebra finches nestlings to BDE-99 and raised them to sexual maturity. •Found no effects on physiology, chick growth, survival, or reproductive success. •As BDE-99 dose increased, laying interval increased. •Passerine birds possibly less sensitive to BDE-99 than mammals or other bird species. -- Nestling exposure to BDE-99 affects timing of breeding in zebra finches, but overall passerines appear to be less sensitive to PBDEs than mammals or other bird species

Nuclear shape changes are induced by knockdown of the SWI/SNF ATPase BRG1 and are independent of cytoskeletal connections.

Directory of Open Access Journals (Sweden)

Karen M Imbalzano

Full Text Available Changes in nuclear morphology occur during normal development and have been observed during the progression of several diseases. The shape of a nucleus is governed by the balance of forces exerted by nuclear-cytoskeletal contacts and internal forces created by the structure of the chromatin and nuclear envelope. However, factors that regulate the balance of these forces and determine nuclear shape are poorly understood. The SWI/SNF chromatin remodeling enzyme ATPase, BRG1, has been shown to contribute to the regulation of overall cell size and shape. Here we document that immortalized mammary epithelial cells show BRG1-dependent nuclear shape changes. Specifically, knockdown of BRG1 induced grooves in the nuclear periphery that could be documented by cytological and ultrastructural methods. To test the hypothesis that the observed changes in nuclear morphology resulted from altered tension exerted by the cytoskeleton, we disrupted the major cytoskeletal networks and quantified the frequency of BRG1-dependent changes in nuclear morphology. The results demonstrated that disruption of cytoskeletal networks did not change the frequency of BRG1-induced nuclear shape changes. These findings suggest that BRG1 mediates control of nuclear shape by internal nuclear mechanisms that likely control chromatin dynamics.

Polybrominated diphenyl ethers and polychlorinated biphenyls in human adipose tissue from New York.

Science.gov (United States)

Johnson-Restrepo, Boris; Kannan, Kurunthachalam; Rapaport, David P; Rodan, Bruce D

2005-07-15

Human adipose tissue samples (n=52) collected in New York City during 2003-2004 were analyzed for the presence of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs). Concentrations of PBDEs in adipose tissues ranged from 17 to 9630 ng/g, lipid wt (median: 77; mean: 399 ng/g, lipid wt; sum all di- through hexaBDE congeners). Average PBDE concentrations in human adipose tissues from New York City were 10- to 100-times greater than those reported for European countries. A concentration of 9630 ng/g, lipid wt, found in a sample of adipose tissue, is one of the highest concentrations reported to date. PBDE 47 (2,2',4,4'-tetraBDE) was the major congener detected in human tissues, followed by PBDE congeners #99 (2,2',4,4',5-penta BDE), 100 (2,2',4,4',6-pentaBDE), and 153 (2,2',4,4',5,5'-hexaBDE). A few individuals contained PBDE 153 as the predominant congener in total PBDE concentrations, suggesting alternative exposure sources, possibly occupational. Principal component analysis of PBDE congener composition in human adipose tissues revealed the presence of five clusters, each characterized by varying composition. No significant difference was found in the concentrations of PBDEs between gender. Concentrations of PBDEs were, on average, similar to those for PCBs in human adipose tissues, and substantially higher when PBDE outliers were retained. PBDE and PCB concentrations were not correlated. PBDE concentrations did not increase with increasing age of the subjects, whereas concentrations of PCBs increased with increasing age in males but not in females in this study. These results suggest differences between PBDEs and PCBs in their sources or time course of exposure and disposition. The presence of comparable or greater concentrations of PBDEs, relative to PCBs, highlights the importance of recentvoluntary and regulatory effortsto cease production of commercial penta- and octa-BDE in North America, although these efforts do not address

Strong adhesion by regulatory T cells induces dendritic cell cytoskeletal polarization and contact-dependent lethargy.

Science.gov (United States)

Chen, Jiahuan; Ganguly, Anutosh; Mucsi, Ashley D; Meng, Junchen; Yan, Jiacong; Detampel, Pascal; Munro, Fay; Zhang, Zongde; Wu, Mei; Hari, Aswin; Stenner, Melanie D; Zheng, Wencheng; Kubes, Paul; Xia, Tie; Amrein, Matthias W; Qi, Hai; Shi, Yan

2017-02-01

Dendritic cells are targeted by regulatory T (T reg) cells, in a manner that operates as an indirect mode of T cell suppression. In this study, using a combination of single-cell force spectroscopy and structured illumination microscopy, we analyze individual T reg cell-DC interaction events and show that T reg cells exhibit strong intrinsic adhesiveness to DCs. This increased DC adhesion reduces the ability of contacted DCs to engage other antigen-specific cells. We show that this unusually strong LFA-1-dependent adhesiveness of T reg cells is caused in part by their low calpain activities, which normally release integrin-cytoskeleton linkage, and thereby reduce adhesion. Super resolution imaging reveals that such T reg cell adhesion causes sequestration of Fascin-1, an actin-bundling protein essential for immunological synapse formation, and skews Fascin-1-dependent actin polarization in DCs toward the T reg cell adhesion zone. Although it is reversible upon T reg cell disengagement, this sequestration of essential cytoskeletal components causes a lethargic state of DCs, leading to reduced T cell priming. Our results reveal a dynamic cytoskeletal component underlying T reg cell-mediated DC suppression in a contact-dependent manner. © 2017 Chen et al.

Diagnostic ability of Tc-99m MIBI SPECT in coronary artery diseases in not affected by the degree of exercise

International Nuclear Information System (INIS)

Lee, Jae Tae; Kim, Jong Soo; Chun, Kyung Ah; Lee, Sang Woo; Kang, Do Young; Cho, Yong Keun; Chae, Shung Chull; Lee, Kyu Bo

1999-01-01

The sensitivity of ST-depression in the electrocardiogram during exercise is influenced by the level of efforts. However, unlike the prevalence of ST-depression of exercise ECG, the degree of exercise is reported to do not influence the diagnostic ability of myocardial perfusion scan. Furthermore, the relation between the prevalence of myocardial ischemia and effort is still controversial. We evaluated the effect of the degree of exercise on the ability of SPECT imaging to detect coronary artery stenosis. The patient population was comprised of 111 patients (73 men and 38 women, mean age 56 years) who underwent an exercise test in conjunction with Tc-99m MIBI and cardiac catheterization within 3 months apart each other. The degree of exercise was classified into four groups according to the percentage of maximal predicted heart rate. The sensitivity and specificity was compared between each group. The overall diagnostic sensitivity was significantly higher with Tc-99m MIBI SPECT than exercise ECG. The specificity was not significantly different between two tests. Sensitivity and specificity of Tc-99m MIBI was not different between four groups. Sensitivity for individual coronary stenosis seemed to be lower in subjects who had premature termination of exercise due to early appearance of ST depression. These results suggest that the overall diagnostic sensitivity of Tc-99m MIBI myocardial perfusion SPECT is not significantly affected by the degree of exercise in stable patients undergoing symptom-limited treadmil exercise testing. Myocardial perfusion SPECT imaging should be added to routine exercise stress testing for the detection of coronary artery disease

Polybrominated diphenyl ethers (PBDEs) in sediments of the coastal East China Sea: Occurrence, distribution and mass inventory

International Nuclear Information System (INIS)

Li Yuanyuan; Lin Tian; Chen Yingjun; Hu Limin; Guo Zhigang; Zhang Gan

2012-01-01

Polybrominated diphenyl ethers (PBDEs) of sixty-three sediment samples from the coastal East China Sea (ECS), extending ∼1000 km from the Yangtze River Estuary to the south, were measured. The levels of BDE-209 and ∑PBDE 7 (sum of BDE-28, 47, 99, 100, 153, 154, 183) were 0.3–44.6 ng/g (dry weight) and nd-8.0 ng/g, respectively. BDE-209 was the predominant congener, followed by BDE-99/100. This was consistent with the historical and current usage of PBDE mixtures in China. The compositions and distribution of PBDEs suggest that the PBDEs in this area could be mainly from the coastal electronic waste dismantling/recycling and Yangtze River input. The poor correlations between TOC, grain size of sediments with PBDEs imply that the PBDE distribution is more related to their land-based inputs rather than the sediment characters in the area. The coastal ECS is an important sink of PBDEs (7.5 t/yr) in the world. - Highlights: ► First report on the levels, distribution and inventory of PBDEs in the inner shelf of the ECS. ► PBDEs were mainly from the coastal electronic waste dismantling/recycling and Yangtze River. ► PBDE distribution was related to the land-based inputs rather than the sediment characters. ► The coastal East China Sea is an important sink of the PBDEs in the world. - The levels, distribution, potential sources and mass inventory of PBDEs in sediments of the coastal East China Sea were revealed.

An embedded system based computer controlled process automation for recovery and purification of 99mTc from (n,γ)99Mo

International Nuclear Information System (INIS)

De, Anirban; Pal, S.S.; Bhaskar, P.; Kumari, S.; Khare, V.K.; Duttaroy, A.; Garai, M.; Thakur, S.K.; Saha, S.; Chattopadhyay, Sankha; Barua, Luna; Das, Sujata Saha; Kumar, U.; Das, M.K.

2012-01-01

99 Mo produced 99 mTc (t 1/2 = 6 hr, 140 KeV γ-ray) is the most useful radioisotope for nuclear diagnostics. High specific activity 99 Mo is supplied globally mainly by five old reactors whose routine or unscheduled maintenance shutdown causes supply irregularities that adversely affects patient management in nuclear medicine centres. 99m Tc may also be produced via 98 Mo(n,γ) in a natural MoO 3 target in reactor or by 100 Mo(n,2n) 99 Mo or 100 Mo(p,2n) 99 mTc reaction in cyclotron. To meet the crisis proposals are there to produce 99 Mo by 100 Mo(n,2n) 99 Mo or 99m Tc directly by 100 Mo(p,2n) 99m Tc in a cyclotron. Of the several separation methods of 99 mTc from molybdenum, the most common are adsorption column chromatography, sublimation and liquid-liquid solvent extraction. The conventional methods besides being cumbersome are often hazardous, polluting, require skilled manpower and facilities like fume hood and so are not always practically feasible for hospitals. To address these, VECC and BRIT, Kolkata have collaborated to develop an embedded system based automated 99 Mo/ 99m Tc generator from low specific activity 99 Mo using solvent extraction technique, supervised by a PC based GUI. (author)

Effect of acidity and chemical composition of sup(99m)Tc-radiopharmaceuticals on sup(99m)Tc accumulation in necrotic tissue of rat myocardium

Energy Technology Data Exchange (ETDEWEB)

Vilcek, S; Machan, V; Kalincak, M [Ustav Radioekologie a Vyuzitia Jadrovej Techniky, Kosice (Czechoslovakia); Nicak, A [Univerzita P.J. Safarika, Kosice (Czechoslovakia). Lekarska Fakulta

1981-04-30

Experiments showed that the cumulation of technetium-99m following the administration of /sup 99m/Tc-Sn-pyrophosphate and s/sup 99m/Tc-Sn-oxytetracycline in the necrotic tissue of rat myocardium damaged by cauterization depended on the end pH value. The maximum /sup 99m/Tc cumulation in the myocardial lesion was noted when the end pH value ranged in 5.5 to 6.0. It appeared that pyrophosphate concentration decrease below the critical limit not only affected the cumulation of /sup 99m/Tc in the particular organs but also in the necrotic tissue of the myocardium.

Effect of acidity and chemical composition of sup(99m)Tc-radiopharmaceuticals on sup(99m)Tc accumulation in necrotic tissue of rat myocardium

International Nuclear Information System (INIS)

Vilcek, S.; Machan, V.; Kalincak, M.; Nicak, A.

1981-01-01

Experiments showed that the cumulation of technetium-99m following the administration of sup(99m)Tc-Sn-pyrophosphate and sup(99m)Tc-Sn-oxytetracycline in the necrotic tissue of rat myocardium damaged by cauterization depended on the end pH value. The maximum sup(99m)Tc cumulation in the myocardial lesion was noted when the end pH value ranged in 5.5 to 6.0. It appeared that pyrophosphate concentration decrease below the critical limit not only affected the cumulation of sup(99m)Tc in the particular organs but also in the necrotic tissue of the myocardium. (author)

Determination of 99Mo contamination in 99mTc elute obtained from 99Mo/99mTc- generator

International Nuclear Information System (INIS)

Momennezhad, M.; Zakavi, S. R.; Sadeghi, R.

2010-01-01

99m Tc is a widely used radioisotope in nuclear medicine centers which is obtained by elution from Mo-99/Tc-99m generators. Usually the generators are either supplied by the Iran Atomic Energy Agency or by private companies from foreign countries. In this study we have measured 99 Mo contamination in 99m Tc elute from different generators in a period of one year. Materials and Methods: The radionuclide impurity of the 99m Tc elute were studied in two types of radionuclide generators (A: produced in Iran and B: Imported from other country). In-vitro measurements were performed using dose calibrator. Direct measurements were made, using a standard canister at the time of milking of the generators and also in Subsequent hours after milking. Results: The results showed a mean of 99 Mo impurity in generators A and B to be 0.00932±0.0043 and 0.0170±0.0127 respectively. Although the results showed that the 99 Mo contamination in 99 mTc elute was lesser than the maximum accepted activity limit of 0.015%, the difference in these two types may reflect different methods of productions of generator, as well as the quality control procedures. Conclusion: The mean of 99 Mo contamination in generators produced in Iran Atomic Energy Organization was lesser than generators imported from foreign origin.

Early cytoskeletal protein modifications precede overt structural degeneration in the DBA/2J mouse model of glaucoma

Directory of Open Access Journals (Sweden)

Gina Nicole Wilson

2016-11-01

Full Text Available Axonal transport deficits precede structural loss in glaucoma and other neurodegenerations. Impairments in structural support, including modified cytoskeletal proteins and microtubule-destabilizing elements, could be initiating factors in glaucoma pathogenesis. We investigated the time course of changes in protein levels and post-translational modifications in the DBA/2J mouse model of glaucoma. Using anterograde tract tracing of the retinal projection, we assessed major cytoskeletal and transported elements as a function of transport integrity in different stages of pathological progression. Using capillary-based electrophoresis, single- and multiplex immunosorbent assays, and immunofluorescence, we quantified hyperphosphorylated neurofilament-heavy chain, phosphorylated tau (ptau, calpain-mediated spectrin breakdown product (145/150kDa, β –tubulin, and amyloid-β42 proteins based on age and transport outcome to the superior colliculus (SC, the main retinal target in mice. Phosphorylated neurofilament-heavy chain (pNF-H was elevated within the optic nerve (ON and SC of 8-10 month-old DBA/2J mice, but was not evident in the retina until 12-15 months, suggesting that cytoskeletal modifications first appear in the distal retinal projection. As expected, higher pNF-H levels in the SC and retina were correlated with axonal transport deficits. Elevations in hyperphosphorylated tau (ptau occurred in ON and SC between 3-8 month of age while retinal ptau accumulations occurred at 12-15 months in DBA/2J mice. In vitro co-immunoprecipitation experiments suggested increased affinity of ptau for the retrograde motor complex protein, dynactin. We observed a transport-related decrease of β-tubulin in ON of 10-12 month-old DBA/2J mice, suggesting destabilized microtubule array. Elevations in calpain-mediated spectrin breakdown product were seen in ON and SC at the earliest age examined, well before axonal transport loss is evident. Finally, transport

Minimizing Molybdenum 99 contamination in Technetium 99m Pertechnetate from the elution of 99Mo/ 99m Tc Generator

International Nuclear Information System (INIS)

Zakaria Ibrahim; Zulkifli Hashim; Bohari Yaacob

2011-01-01

Radioisotope Tc-99m is widely used for variety of nuclear medicine diagnostic procedures. For many commercial applications, it is prepared in a portable type generator. Nuclear Malaysia has been producing a dry type alumina chromatographic column generator utilizing fission Mo-99. This injectable Tc-99m must meet the British Pharmacopeia [1] product specification prior to be apply on patient. This paper provides a method to minimize the up to acceptable level Mo-99 in the final product. Purposely made pertechnetate contaminated with Mo-99 and re-eluate by using old generator. Excellent removal of Mo-99 impurity was achieved and more than 80 % of Tc-99m total activity was recovered. (author)

Spent 99Mo/99mTc generator as an economical source of 99Mo

International Nuclear Information System (INIS)

El-Kolaly, M.T.

1990-01-01

An improved method for utilization and purification of 99 Mo from spent 90 Mo/ 99m Tc generators has been described. After washing the generator with saline to remove the generated 99m Tc, followed by 2 mL 5 M NaOH containing a few drops of H 2 O 2 , the 99 Mo was quantitatively eluted from the generator with 5 mL 5 M NaOH. The alkaline eluate containing 99 Mo was contaminated with partially dissolved alumina. In the present method, an anion-exchange resin Dowex 1 x 8 column was used for purification of 99 Mo from the contaminating alumina. The resultant 99 Mo was of high purity and contained 3+ /mL 99 Mo solution, as estimated by atomic absorption. (author)

Effect of collagen I and fibronectin on the adhesion, elasticity and cytoskeletal organization of prostate cancer cells

Energy Technology Data Exchange (ETDEWEB)

Docheva, Denitsa [Experimental Surgery and Regenerative Medicine, Department of Surgery, Ludwig-Maximilians-University (LMU), Nussbaumstr. 20, 80336 Munich (Germany); Padula, Daniela [Experimental Surgery and Regenerative Medicine, Department of Surgery, Ludwig-Maximilians-University (LMU), Nussbaumstr. 20, 80336 Munich (Germany); Department of Precision- and Micro-Engineering, Engineering Physics, Munich University of Applied Sciences, Lothstr. 34, 80335 Munich (Germany); Center for NanoScience (CeNS), Geschwister-Scholl-Platz 1, 80539 Munich (Germany); Schieker, Matthias, E-mail: matthias.schieker@med.uni-muenchen.de [Experimental Surgery and Regenerative Medicine, Department of Surgery, Ludwig-Maximilians-University (LMU), Nussbaumstr. 20, 80336 Munich (Germany); Clausen-Schaumann, Hauke, E-mail: clausen-schaumann@hm.edu [Department of Precision- and Micro-Engineering, Engineering Physics, Munich University of Applied Sciences, Lothstr. 34, 80335 Munich (Germany); Center for NanoScience (CeNS), Geschwister-Scholl-Platz 1, 80539 Munich (Germany)

2010-11-12

Research highlights: {yields} Depending on the metastatic origin, prostate cancer cells differ in their affinity to COL1. {yields} COL1 affects specifically the F-actin and cell elasticity of bone-derived prostate cancer cells. {yields} Cell elasticity can be used as a biomarker for cancer cells from different metastases. -- Abstract: Despite of intensive research efforts, the precise mechanism of prostate cancer metastasis in bone is still not fully understood. Several studies have suggested that specific matrix production by the bone cells, such as collagen I, supports cancer cell invasion. The aim of this study was to investigate the effect of collagen I (COL1) and fibronectin (FN) on cell adhesion, cell elasticity and cytoskeletal organization of prostate cancer cells. Two cell lines, bone marrow- (PC3) and lymph node-derived (LNCaP) were cultivated on COL1 and FN (control protein). By using a quantitative adhesion assay and time-lapse analysis, it was found that PC3, but not LNCaP, adhered strongly and were more spread on COL1. Next, PC3 and LNCaP were evaluated by atomic force microscopy (AFM) and flatness shape factor and cellular Young's modulus were calculated. The shape analysis revealed that PC3 were significantly flatter when grown on COL1 in comparison to LNCaP. In general, PC3 were also significantly stiffer than LNCaP and furthermore, their stiffness increased upon interaction with COL1. Since cell stiffness is strongly dependent on actin organization, phalloidin-based actin staining was performed and revealed that, of the two cell types as well as the two different matrix proteins, only PC3 grown on COL1 formed robust actin cytoskeleton. In conclusion, our study showed that PC3 cells have a strong affinity towards COL1. On this matrix protein, the cells adhered strongly and underwent a specific cell flattening. Moreover, with the establishment of PC3 contact to COL1 a significant increase of PC3 stiffness was observed due to a profound

Estimation of the source strength of polybrominated diphenyl ethers based on their diel variability in air in Zurich, Switzerland.

Science.gov (United States)

Moeckel, Claudia; Gasic, Bojan; MacLeod, Matthew; Scheringer, Martin; Jones, Kevin C; Hungerbühler, Konrad

2010-06-01

Diel (24-h) concentration variations of polybrominated diphenyl ethers (PBDEs) in air were measured in the center of Zurich, Switzerland, and on Uetliberg, a hill about 5 km from the city center. Air samples were collected simultaneously at both sites over 4 h time periods for 3 consecutive days during a stable high pressure system in August 2007. Higher PBDE concentrations in the city compared to the Uetliberg site indicate that Zurich is a likely source of PBDEs to the atmosphere. A multimedia mass balance model was used to (i) explain the diel cycling pattern of PBDE concentrations observed at both sites in terms of dominant processes and (ii) estimate emission rates of PBDEs from the city to the atmosphere. We estimate that Zurich emits 0.4, 6.2, 1.6, and 0.4 kg year(-1) of the PBDE congeners 28, 47, 99, and 100, respectively. On a per-capita basis, these estimates are within the range or somewhat above those obtained in other studies using approaches based on emission factors (EF) and PBDE production, usage, and disposal data, or concentration measurements. The present approach complements emission estimates based on the EF approach and can also be applied to source areas where EFs and PBDE material flows are poorly characterized or unknown, such as electronic waste processing plants.

Polybrominated diphenyl ethers and polychlorinated biphenyls in sediments of southwest Taiwan: Regional characteristics and potential sources

International Nuclear Information System (INIS)

Jiang, Jheng-Jie; Lee, Chon-Lin; Fang, Meng-Der; Ko, Fung-Chi; Baker, Joel E.

2011-01-01

Research highlights: → This paper presents the very first PBDE and PCB study in coastal sediment of Taiwan. → Compositional patterns indicated deca-BDE and octa-BDE products as dominant sources. → The possible source of PBDE may be the nearby electric/electronic industry in Taiwan. → PCB signatures suggested the legacy of past use of commercial PCB mixtures in Taiwan. - Abstract: Very little information is available on the contamination of coastal sediments of Taiwan by PBDEs and PCBs. In this study, we determined the concentrations of 19 PBDE and 209 PCB congeners in 57 surface sediment samples to identify the possible sources of PBDEs and PCBs. The total PBDE and PCB concentrations ranged from below detection limit to 7.73 ng/g and 0.88-7.13 ng/g, respectively; these values are within the ranges observed for most coastal sediments worldwide. The PBDE congeners were dominated by BDE-209 (50.7-99.7%), with minor contributions from penta- and octa-BDEs. The signatures of PCB congeners suggested that PCB residues in Kaohsiung coast may be the legacy of past use or the result of ongoing inputs from the maintenance, repair and salvage of old ships. Principal component analysis of the congener-specific composition of PBDEs and PCBs revealed distinct regional patterns that are related to the use of commercial products.

Current levels of primary polybrominated diphenyl ethers (PBDEs) in Norwegian seafood

Energy Technology Data Exchange (ETDEWEB)

Bethune, C.; Nielsen, J.; Julshamn, K. [National Institute of Nutrition and Seafood Research, Bergen (Norway)

2004-09-15

The brominated flame retardants (BFRs) represent major industrial chemicals whose use has increased dramatically over the past few decades. Polybrominated diphenyl ethers (PBDEs) are BFRs that are used in many types of consumer products. PBDEs have come to the attention of regulators and scientists due to their bioaccumulation, increasing exposure and persistence in the environment, and adverse health effects in animals and humans. Although PBDE contamination in marine fish was first detected in Sweden in 1979, and certain PBDEs are now banned as of this year, the European Union has yet to establish regulations on PBDE levels in either feed or seafood. The determination of these contaminants in consumer seafood is important for dietary exposure assessment and protection of human health. This study reports on the levels of 6 prominent PBDE congeners (28, 47, 99, 100, 153, and 154) in a selection of common Norwegian seafood.

Evaluation of fresh and old eluate of 99Mo/99mTc generators used for labeling of different pharmaceutical kits

International Nuclear Information System (INIS)

Urbano, N.; Chinol, M.; Modoni, S.; Guerra, M.

2005-01-01

Sixty 99 Mo/ 99m Tc wet column generators, loaded with two different 99 Mo activities, were analyzed in order to assess the quality of their eluates. Each elution was used for labeling of different radiopharmaceuticals, in order to evaluate whether 'risky' elutions, namely those performed just after generator delivery and at 72 hours or more from the last elution, could be conveniently employed when fresh available radioactivity is not enough for the planned labeling or when shipping problems arise, or delay in delivery of a new generator occurs. Radiochemical quality control of all radiopharmaceuticals labeled with these elutions was performed. The elutions differed mainly in 99 Tc ground state ( 99g Tc) and amounts of oxidizing impurities. Radiolabeling procedures, however, were not affected, suggesting that these 'risky' elutions might be appropriately used, in 'emergency' conditions, for labeling radiopharmaceuticals although their radiochemical purity control is recommended prior to patient administration. (author)

Novelty-induced activity-regulated cytoskeletal-associated protein (Arc) expression in frontal cortex requires serotonin 2A receptor activation

DEFF Research Database (Denmark)

Santini, Martin; Klein, A B; El-Sayed, M

2011-01-01

environment. As an output of FC activation we measured expression of activity-regulated cytoskeletal-associated protein (Arc). Novelty-exposure (open-field arena) robustly up-regulated FC Arc mRNA expression (∼160%) in mice compared to home-cage controls. This response was inhibited with the 5-HT(2A...

Novelty-induced activity-regulated cytoskeletal-associated protein (Arc) expression in frontal cortex requires serotonin 2A receptor activation

DEFF Research Database (Denmark)

Santini, Martin; Klein, A B; El-Sayed, M

2011-01-01

environment. As an output of FC activation we measured expression of activity-regulated cytoskeletal-associated protein (Arc). Novelty-exposure (open-field arena) robustly up-regulated FC Arc mRNA expression (~160%) in mice compared to home-cage controls. This response was inhibited with the 5-HT(2A...

Fate of polybrominated diphenyl ethers in the environment of the Pearl River Estuary, South China

International Nuclear Information System (INIS)

Guan Yufeng; Sojinu, O.S. Samuel; Li Shaomeng; Zeng, Eddy Y.

2009-01-01

Ninety-six riverine runoff samples collected at eight major outlets in the Pearl River Delta (PRD), South China, during 2005-2006 were analyzed for 17 brominated diphenyl ether (BDE) congeners (defined as Σ 17 PBDE). Fourteen and 15 congeners were detected, respectively, in the dissolved and particulate phases. These data were further used to elucidate the partitioning behavior of BDE congeners in riverine runoff. Several related fate processes, i.e. air-water exchange, dry and wet deposition, degradation, and sedimentation, within the Pearl River Estuary (PRE), were examined to estimate the inputs of Σ 10 PBDE (sum of the target BDE congeners, BDE-28, -47, -66, -85, -99, -100, -138, -153, -154, and -183) and BDE-209 from the PRD to the coastal ocean based on mass balance considerations. The results showed that annual outflows of Σ 10 PBDE and BDE-209 were estimated at 126 and 940 kg/year, respectively from the PRE to coastal ocean. Besides sedimentation and degradation, the majority of Σ 10 PBDE and BDE-209 discharged into the PRE via riverine runoff was transported to the coastal ocean. - Fate of polybrominated diphenyl ethers in the environment the Pearl River Estuary, South China.

40 CFR 86.1729-99-86.1733-99 - [Reserved

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 19 2010-07-01 2010-07-01 false [Reserved] 86.1729-99-86.1733-99 Section 86.1729-99-86.1733-99 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Light-Duty Trucks §§ 86.1729-99—86.1733-99 [Reserved] ...

40 CFR 86.1736-99-86.1769-99 - [Reserved

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 19 2010-07-01 2010-07-01 false [Reserved] 86.1736-99-86.1769-99 Section 86.1736-99-86.1769-99 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Light-Duty Trucks §§ 86.1736-99—86.1769-99 [Reserved] ...

40 CFR 86.1718-99-86.1720-99 - [Reserved

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 19 2010-07-01 2010-07-01 false [Reserved] 86.1718-99-86.1720-99 Section 86.1718-99-86.1720-99 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Light-Duty Trucks §§ 86.1718-99—86.1720-99 [Reserved] ...

Active Polar Gels: a Paradigm for Cytoskeletal Dynamics

Science.gov (United States)

Julicher, Frank

2006-03-01

The cytoskeleton of eucaryotic cells is an intrinsically dynamic network of rod-like filaments. Active processes on the molecular scale such as the action of motor proteins and the polymerization and depolymerization of filaments drive active dynamic behaviors while consuming chemical energy in the form of a fuel. Such emergent dynamics is regulated by the cell and is important for many cellular processes such as cell locomotion and cell division. From a general point of view the cytoskeleton represents an active gel-like material with interesting material properties. We present a general theory of active viscoelastic materials made of polar filaments which is motivated by the the cytoskeleton. The continuous consumption of a fuel generates a non- equilibrium state characterized by the generation of flows and stresses. Our theory can be applied to experiments in which cytoskeletal patterns are set in motion by active processes such as those which are at work in cells. It can also capture generic aspects of the flows and stress profiles which occur during cell locomotion.

Successful labeling of 99mTc-MDP using 99mTc separated from 99Mo produced by 100Mo(n,2n)99Mo

International Nuclear Information System (INIS)

Nagai, Yasuki; Hatsukawa, Yuichi; Kin, Tadahiro; Hashimoto, Kazuyuki; Motoishi, Shoji; Konno, Chikara; Ochiai, Kentaro; Takakura, Kosuke; Sato, Yuichi; Sato, Norihito; Ohta, Akio; Yamabayashi, Hisamichi; Tanase, Masakazu; Fujisaki, Saburo; Kawauchi, Yukimasa; Teranaka, Tomoyuki; Takeuchi, Nobuhiro; Igarashi, Takashi

2011-01-01

We have for the first time succeeded in separating 99m Tc from a MoO 3 sample irradiated with accelerator neutrons free from any radioactive impurities and in formulating 99m Tc-methylene diphosphonate ( 99 mTc-MDP). 99 Mo, the mother nuclide of 99m Tc, was produced by the 100 Mo(n,2n) 99 Mo reaction using about 14 MeV neutrons provided by the 3 H(d,n) 4 He reaction at the Fusion Neutronics Source of Japan Atomic Energy Agency. The 99m Tc was separated from 99 Mo by sublimation and its radionuclide purity was confirmed to be higher than 99.99% by γ-spectroscopy. The labeling efficiency of 99m Tc-MDP was shown to be higher than 99% by thin-layer chromatography. These values exceed the United States Pharmacopeia requirements for a fission product, 99 Mo. Consequently, a 99m Tc radiopharmaceutical preparation formed by using the mentioned 99 Mo can be a promising substitute for the fission product 99 Mo, which is currently produced using a highly enriched uranium target in aging research reactors. A longstanding problem to ensure a reliable and constant supply of 99 Mo in Japan can be partially mitigated. (author)

Production optimization of {sup 99}Mo/{sup 99m}Tc zirconium molybate gel generators at semi-automatic device: DISIGEG

Energy Technology Data Exchange (ETDEWEB)

Monroy-Guzman, F., E-mail: fabiola.monroy@inin.gob.mx [Instituto Nacional de Investigaciones Nucleares, Carretera Mexico-Toluca S/N, La Marquesa, Ocoyoacac, 52750, Estado de Mexico (Mexico); Rivero Gutierrez, T., E-mail: tonatiuh.rivero@inin.gob.mx [Instituto Nacional de Investigaciones Nucleares, Carretera Mexico-Toluca S/N, La Marquesa, Ocoyoacac, 52750, Estado de Mexico (Mexico); Lopez Malpica, I.Z.; Hernandez Cortes, S.; Rojas Nava, P.; Vazquez Maldonado, J.C. [Instituto Nacional de Investigaciones Nucleares, Carretera Mexico-Toluca S/N, La Marquesa, Ocoyoacac, 52750, Estado de Mexico (Mexico); Vazquez, A. [Instituto Mexicano del Petroleo, Eje Central Norte Lazaro Cardenas 152, Col. San Bartolo Atepehuacan, 07730, Mexico D.F. (Mexico)

2012-01-15

DISIGEG is a synthesis installation of zirconium {sup 99}Mo-molybdate gels for {sup 99}Mo/{sup 99m}Tc generator production, which has been designed, built and installed at the ININ. The device consists of a synthesis reactor and five systems controlled via keyboard: (1) raw material access, (2) chemical air stirring, (3) gel dried by air and infrared heating, (4) moisture removal and (5) gel extraction. DISIGEG operation is described and dried condition effects of zirconium {sup 99}Mo- molybdate gels on {sup 99}Mo/{sup 99m}Tc generator performance were evaluated as well as some physical-chemical properties of these gels. The results reveal that temperature, time and air flow applied during the drying process directly affects zirconium {sup 99}Mo-molybdate gel generator performance. All gels prepared have a similar chemical structure probably constituted by three-dimensional network, based on zirconium pentagonal bipyramids and molybdenum octahedral. Basic structural variations cause a change in gel porosity and permeability, favouring or inhibiting {sup 99m}TcO{sub 4}{sup -} diffusion into the matrix. The {sup 99m}TcO{sub 4}{sup -} eluates produced by {sup 99}Mo/{sup 99m}Tc zirconium {sup 99}Mo-molybdate gel generators prepared in DISIGEG, air dried at 80 Degree-Sign C for 5 h and using an air flow of 90 mm, satisfied all the Pharmacopoeias regulations: {sup 99m}Tc yield between 70-75%, {sup 99}Mo breakthrough less than 3 Multiplication-Sign 10{sup -3}%, radiochemical purities about 97% sterile and pyrogen-free eluates with a pH of 6. - Highlights: Black-Right-Pointing-Pointer {sup 99}Mo/{sup 99m}Tc generators based on {sup 99}Mo-molybdate gels were synthesized at a semi-automatic device. Black-Right-Pointing-Pointer Generator performances depend on synthesis conditions of the zirconium {sup 99}Mo-molybdate gel. Black-Right-Pointing-Pointer {sup 99m}TcO{sub 4}{sup -} diffusion and yield into generator depends on gel porosity and permeability. Black

Studies of the retention mechanism of the brain perfusion imaging agent 99m Tc-bicisate (99m Tc-ECD)

International Nuclear Information System (INIS)

Walovitch, R.C.; Cheesman, E.H.; Maheu, L.J.; Hall, K.M.

1994-01-01

The structure-activity relationship in a series of analogues of 99m T c -bicisate ( 99m T c -N,N'-1,2-ethylene-diylbis-L-cysteine diethyl ester dihydrochloride, RP-217) is described using in vivo studies in rodent and primate brain tissue. All analogues investigated were 99m T c -diamine dithiol diesters, which were neutral and lipophilic and had modified brain uptake indexes (≥40) suggesting adequate first-pass extraction. All analogues were poorly retained by the rodent brain. In contrast, the stereochemistry and structure of the 99m T c -complexes affected their brain retention in primates. All compounds that demonstrated selective primate brain retention were L-diesters that were metabolized in primate brain tissue to nonlypophilic complexes resulted from ester hydrolysis. Unretained complexes were not metabolized in primate brain tissue. More extensive studies were performed with 99m T c -bicisate, which demonstrated poor brain retention in several nonprimate species (i.e., dogs, ferrets, pigs, and rodents). In rodent and nonhuman primate tissue, 99m T c -bicisate was rapidly metabolized to a monoacid ester ( 99m T c -N,N'-1,2-ethylenediylbis-L-cysteine monoethyl ester). Therefore, brain metabolism of 99m T c -bicisate results in the formation of an acid product(s) that is selectively trapped in primate brain. 20 refs., 2 figs., 4 tabs

Distribution of cytoskeletal proteins, integrins, leukocyte adhesion molecules and extracellular matrix proteins in plastic-embedded human and rat kidneys

NARCIS (Netherlands)

van Goor, H; Coers, W; van der Horst, MLC; Suurmeijer, AJH

2001-01-01

OBJECTIVE: To study the distribution of cytoskeletal proteins (actin, alpha -actinin, vinculin, beta -tubulin, keratin, vimentin, desmin), adhesion molecules for cell-matrix interations (very later antigens [VLA1-6], beta1, beta2 [CD18], vitronectin receptor [alphav beta3], CD 11b), leukocyte

Induction of Plant Curvature by Magnetophoresis and Cytoskeletal Changes during Root Graviresponse

Science.gov (United States)

Hasenstein, Karl H.; Kuznetsov, Oleg A.; Blancaflor, Eilson B.

1996-01-01

High gradient magnetic fields (HGMF) induce curvature in roots and shoots. It is considered that this response is likely to be based on the intracellular displacement of bulk starch (amyloplasts) by the ponderomotive force generated by the HGMF. This process is called magnetophoresis. The differential elongation during the curvature along the concave and convex flanks of growing organs may be linked to the microtubular and/or microfilament cytoskeleton. The possible existence of an effect of the HGMF on the cytoskeleton was tested for, but none was found. The application of cytoskeletal stabilizers or depolymerizers showed that neither microtubules, nor microfilaments, are involved in the graviresponse.

Radiochemical purity and in vitro stability of Tc-99m radiopharmaceuticals

International Nuclear Information System (INIS)

Vucina, J.

2001-01-01

The increased contents of long lived 99 Tc, oxygen and cupric ions could affect the labeling yield of eight radiopharmaceuticals. Oxygen and in leaser extend copper were found to affect the radiochemical purity of the preparations. In vitro stability of radiopharmaceuticals, examined on 99m Tc(Sn)-pyrosphoshate solutions, was extended when ascorbic acid was added as the chemical stabilizer. The quantity of 5x10 -7 mol/dm 3 of ascorbic acid was found to be sufficient to keep the content of 99m Tc-pertechnetate below 1 % six hours after labeling even in the cases when 99m Tc was present in high radioactive concentrations (740-814 GBq/dm 3 ). The results led to the development of the kits in which ascorbic or gentisic acid are the standards component in the kit composition (author)

Temporal trends of polybrominated diphenyl ethers (PBDEs) in the blood of newborns from New York State during 1997 through 2011: analysis of dried blood spots from the newborn screening program.

Science.gov (United States)

Ma, Wan-Li; Yun, Sehun; Bell, Erin M; Druschel, Charlotte M; Caggana, Michele; Aldous, Kenneth M; Buck Louis, Germaine M; Kannan, Kurunthachalam

2013-07-16

Polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental pollutants, and on a global basis, North American populations are exposed to the highest doses of PBDEs. In response to the exponential increase in human exposure to PBDEs during the late 1990s, some PBDE formulations were phased out from production in the early 2000s. The effectiveness of the phase-out of commercial penta-BDE and octa-BDE mixtures in 2004 in the U.S. on human exposure levels is not known. Dried blood spots (DBSs), collected for the newborn screening program (NSP) in the U.S., are a valuable resource for the elucidation of trends in exposure to environmental pollutants in newborns. In this study, seven PBDE congeners were determined by gas chromatography-high resolution mass spectrometry (GC-HRMS) in archived DBS samples (in total, 51 blood spot composites from 1224 newborns) collected from newborns in New York State (NYS) from 1997 to 2011. The most frequently detected PBDE congener was BDE-47, with a detection rate (DR) of 86%, followed by BDE-99 (DR: 45%) and BDE-100 (DR: 43%). The mean concentrations determined during 1997 through 2011 in the whole blood of newborns were 0.128, 0.040, and 0.012 ng/mL for BDE-47, -99, and -100, respectively. A significant correlation was found among the concentrations of three major congeners (p < 0.001). PBDE concentrations were similar during 1997 through 2002 and, thereafter, decreased significantly, which was similar to the trends observed for perfluorinated compounds (PFCs) in DBS samples. Occurrence of PBDEs in the whole blood of newborns confirms that these compounds do cross the placental barrier.

The Use of Sodium Hypochlorite Solution for (n,γ99Mo/99mTc Generator Based on Zirconium-Based Material (ZBM

Directory of Open Access Journals (Sweden)

I. Saptiama

2015-08-01

Full Text Available The many problems in preparing fission product 99Mo led into this work to develop 99Mo/99mTc generator using neutron-irradiated natural MoO3 targets and, more specifically, to develop a zirconium-based material (ZBM for chromatography columns that have an adsorption capacity of more than 100 mg Mo/g ZBM. This paper reports our recent experiments in the use of sodium hypochlorite solution of various concentrations to improve the yield of 99mTc in performance of (n,γ99Mo/99mTc generators based on the ZBM. The synthesized ZBM was coated with tetraethyl orthosilicate for improving the hardness of the material. The adsorption of [99Mo]molybdate into ZBM was carried out by reacting ZBM into [99Mo]molybdate solution at 90°C to form ZBM-[99Mo] molybdate. ZBM-[99Mo]molybdate was then packed into generator column, then eluted with 10 × 1 mL of saline followed by 1 × 5 mL of NaOCl solution. The NaOCl solution concentrations used were 0.5%; 1%; 3%; and 5% for each column, respectively. This study resulted in a ZBM which has a 99Mo adsorption capacity of 167.5 ± 3.4 mgMo/g ZBM, as well as in a yield eluate of 99mTc of up to 70%, and the find that the optimum NaOCl concentration was 3%. The use of sodium hypochlorite solution affected 99Mo breakthrough. The higher sodium hypochlorite concentration used, the more 99Mo breaktrough exist on 99mTc eluate.

Effect of milking efficiency on Tc-99 content of Tc-99m derived from Tc-99m generators

International Nuclear Information System (INIS)

Bonnyman, J.

1983-01-01

Tc-99m obtained by separation from its parent Mo-99 always contains Tc-99 produced by decay of Tc-99m and Mo-99. Factors effecting the Tc-99/Tc-99m ratios are discussed. An HPLC method has been developed to measure the 99 TcO 4- content of sodium pertechnetate from generators with a detection limit of 0.9 ng Tc-99 for a 500 μl/ aliquot of TcO 4- -99m. First eluates of 10 chromatograph-ic generators gave Tc-99/Tc-99m ratios ranging from 3.5-46 ng Tc/mCi Tc-99m measured at the time of milking. The measurements indicate that Tc-99/Tc-99m ratios high enough to cause adverse labelling effects could be found in 'instant pertechnetate' and in the first eluate from Tc-99m generators for the activities normally used in radiopharmaceutical production

Production technologies for molybdenum-99 and technetium-99m

International Nuclear Information System (INIS)

1999-02-01

Technetium-99m (6.02 h) is the most widely used radioisotope in nuclear medicine, accounting for more than 80% of all diagnostic nuclear medicine procedures. It is almost exclusively produced from the decay of its parent 99 Mo. The present sources of 99 Mo are research reactors by using the (n,γ) nuclear reaction with natural Mo ( 98 Mo, ∼24%), resulting in inexpensive but low-specific activity 99 Mo, or by neutron-induced fission of 235 U, which results in expensive but high specific activity 99 Mo. This publication covers several aspects related to the production of 99 Mo and 99m Tc. The contributed papers reflect the current status of the technology and discuss potential alternative methodologies for the production of 99 Mo and 99m Tc for medical use. The first four papers address the technologies using nuclear reactors, including the description of a new method using an aqueous homogenous reactor core for production of fission 99 Mo and the latest development efforts to fabricate 235 U low enriched targets (LEU, 235 U). The next five papers discuss the potential of utilizing particle accelerators and assess the current status of the available nuclear data for the production of both, 99 Mo and 99m Tc with proton and deuteron beams. The last paper discusses a new technology based on gel system for the preparation of 99 Mo/ 99m Tc generators using low specific activity 99 Mo produced in research reactors by the neutron activation of natural and inexpensive molybdenum oxide targets. Each individual paper was indexed and abstracted

Lysophosphatidic acid receptor activation affects the C13NJ microglia cell line proteome leading to alterations in glycolysis, motility, and cytoskeletal architecture

Science.gov (United States)

Bernhart, Eva; Kollroser, Manfred; Rechberger, Gerald; Reicher, Helga; Heinemann, Akos; Schratl, Petra; Hallström, Seth; Wintersperger, Andrea; Nusshold, Christoph; DeVaney, Trevor; Zorn-Pauly, Klaus; Malli, Roland; Graier, Wolfgang; Malle, Ernst; Sattler, Wolfgang

2014-01-01

Microglia, the immunocompetent cells of the CNS, are rapidly activated in response to injury and microglia migration towards and homing at damaged tissue plays a key role in CNS regeneration. Lysophosphatidic acid (LPA) is involved in signaling events evoking microglia responses through cognate G protein-coupled receptors. Here we show that human immortalized C13NJ microglia express LPA receptor subtypes LPA1, LPA2, and LPA3 on mRNA and protein level. LPA activation of C13NJ cells induced Rho and extracellular signal-regulated kinase activation and enhanced cellular ATP production. In addition, LPA induced process retraction, cell spreading, led to pronounced changes of the actin cytoskeleton and reduced cell motility, which could be reversed by inhibition of Rho activity. To get an indication about LPA-induced global alterations in protein expression patterns a 2-D DIGE/LC-ESI-MS proteomic approach was applied. On the proteome level the most prominent changes in response to LPA were observed for glycolytic enzymes and proteins regulating cell motility and/or cytoskeletal dynamics. The present findings suggest that naturally occurring LPA is a potent regulator of microglia biology. This might be of particular relevance in the pathophysiological context of neurodegenerative disorders where LPA concentrations can be significantly elevated in the CNS. PMID:19899077

Characterization of cytoskeletal and junctional proteins expressed by cells cultured from human arachnoid granulation tissue

Directory of Open Access Journals (Sweden)

Mehta Bhavya C

2005-10-01

Full Text Available Abstract Background The arachnoid granulations (AGs are projections of the arachnoid membrane into the dural venous sinuses. They function, along with the extracranial lymphatics, to circulate the cerebrospinal fluid (CSF to the systemic venous circulation. Disruption of normal CSF dynamics may result in increased intracranial pressures causing many problems including headaches and visual loss, as in idiopathic intracranial hypertension and hydrocephalus. To study the role of AGs in CSF egress, we have grown cells from human AG tissue in vitro and have characterized their expression of those cytoskeletal and junctional proteins that may function in the regulation of CSF outflow. Methods Human AG tissue was obtained at autopsy, and explanted to cell culture dishes coated with fibronectin. Typically, cells migrated from the explanted tissue after 7–10 days in vitro. Second or third passage cells were seeded onto fibronectin-coated coverslips at confluent densities and grown to confluency for 7–10 days. Arachnoidal cells were tested using immunocytochemical methods for the expression of several common cytoskeletal and junctional proteins. Second and third passage cultures were also labeled with the common endothelial markers CD-31 or VE-cadherin (CD144 and their expression was quantified using flow cytometry analysis. Results Confluent cultures of arachnoidal cells expressed the intermediate filament protein vimentin. Cytokeratin intermediate filaments were expressed variably in a subpopulation of cells. The cultures also expressed the junctional proteins connexin43, desmoplakin 1 and 2, E-cadherin, and zonula occludens-1. Flow cytometry analysis indicated that second and third passage cultures failed to express the endothelial cell markers CD31 or VE-cadherin in significant quantities, thereby showing that these cultures did not consist of endothelial cells from the venous sinus wall. Conclusion To our knowledge, this is the first report of

[99mTc[TRODAT-1: a novel technetium-99m complex as a dopamine transporter imaging agent

International Nuclear Information System (INIS)

Kung Meiping; Stevenson, D.A.; Ploessl, K.; Meegalla, S.K.; Beckwith, A.; Essman, W.D.; Mu, M.; Lucki, I.; Kung, H.F.

1997-01-01

Technetium-99m is the most commonly used radionuclide in routine nuclear medicine imaging procedures. Development of 99m Tc-labeled receptor-specific imaging agents for studying the central nervous system is potentially useful for evaluation of brain function in normal and disease states. A novel 99m Tc-labeled tropane derivative, [ 99m Tc[TRODAT-1, which is useful as a potential CNS dopamine transporter imaging agent, was evaluated and characterized. After i.v. injection into rats, [ 99m Tc[TRODAT-1 displayed specific brain uptake in the rat striatal region (striatum-cerebellum/cerebellum ratio 1.8 at 60 min), where dopamine neurons are concentrated. The specific striatal uptake could be blocked by pretreating rats with a dose of competing dopamine transporter ligand, β-CIT (or RTI-55, i.v., 1 mg/kg). However, the specific striatal uptake of [ 99m Tc[TRODAT-1 was not affected by co-injection of excess free ligand (TRODAT-1, up to 200 μg per rat) or by pretreating the rats with haloperidol (i.v., 1 mg/kg). The specific uptake in striatal regions of rats that had prior 6-hydroxydopamine lesion in the substantia nigra area showed a dramatic reduction. The radioactive material recovered from the rat striatal homogenates at 60 min after i.v. injection of [ 99m Tc[TRODAT-1 showed primarily the original compound (>95%), a good indication of in vivo stability in brain tissue. Similar and comparable organ distribution patterns and brain regional uptakes of [ 99m Tc[TRODAT-1 were obtained for male and female rats. (orig./AJ). With 4 figs., 6 tabs

Polybrominated diphenyl ethers in South China maternal and fetal blood and breast milk

Energy Technology Data Exchange (ETDEWEB)

Bi Xinhui [State Key Laboratory of Organic Geochemistry, Guangdong Key Laboratory of Environment and Resources, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); Qu Weiyue [State Key Laboratory of Organic Geochemistry, Guangdong Key Laboratory of Environment and Resources, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); Sheng Guoying [State Key Laboratory of Organic Geochemistry, Guangdong Key Laboratory of Environment and Resources, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); School of Environment and Chemical Engineering, Shanghai University, Shanghai 200072 (China); Zhang Wenbing [State Key Laboratory of Organic Geochemistry, Guangdong Key Laboratory of Environment and Resources, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); Mai Bixian [State Key Laboratory of Organic Geochemistry, Guangdong Key Laboratory of Environment and Resources, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); Chen Dunjin [Obstetrical and Gynecological Institute, Guangzhou Second People' s Hospital, Guangzhou 510150 (China); Yu Lin [Obstetrical and Gynecological Institute, Guangzhou Second People' s Hospital, Guangzhou 510150 (China); Fu Jiamo [State Key Laboratory of Organic Geochemistry, Guangdong Key Laboratory of Environment and Resources, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China) and School of Environment and Chemical Engineering, Shanghai University, Shanghai 200072 (China)]. E-mail: fujm@gig.ac.cn

2006-12-15

Twenty-one-paired human fetal and maternal serum and 27 breast milk samples at South China were analyzed for concentrations of polybrominated diphenyl ethers (PBDEs). Seven PBDE congeners (BDE-28, -47, -99, -100, -153, -154, and -183) were quantified using gas chromatography/mass spectrometry (GC/MS). This is the first report to present the residue levels of PBDEs in human samples of China. The concentrations of total PBDEs ranged from 1.5 to 17 ng/g in the samples and were within the range reported in European samples for a similar population, but lower than human tissue levels in North America. BDE-47 and -153 were the dominant PBDE congeners in all samples and accounted for 60% of the total PBDEs. Further research is needed to determine the exposure route of PBDEs and their health effects. - A survey of PBDE concentrations in human blood and milk helps identify background concentrations in South China population.

ATG5 overexpression is neuroprotective and attenuates cytoskeletal and vesicle-trafficking alterations in axotomized motoneurons.

Science.gov (United States)

Leiva-Rodríguez, Tatiana; Romeo-Guitart, David; Marmolejo-Martínez-Artesero, Sara; Herrando-Grabulosa, Mireia; Bosch, Assumpció; Forés, Joaquim; Casas, Caty

2018-05-24

Injured neurons should engage endogenous mechanisms of self-protection to limit neurodegeneration. Enhancing efficacy of these mechanisms or correcting dysfunctional pathways may be a successful strategy for inducing neuroprotection. Spinal motoneurons retrogradely degenerate after proximal axotomy due to mechanical detachment (avulsion) of the nerve roots, and this limits recovery of nervous system function in patients after this type of trauma. In a previously reported proteomic analysis, we demonstrated that autophagy is a key endogenous mechanism that may allow motoneuron survival and regeneration after distal axotomy and suture of the nerve. Herein, we show that autophagy flux is dysfunctional or blocked in degenerated motoneurons after root avulsion. We also found that there were abnormalities in anterograde/retrograde motor proteins, key secretory pathway factors, and lysosome function. Further, LAMP1 protein was missorted and underglycosylated as well as the proton pump v-ATPase. In vitro modeling revealed how sequential disruptions in these systems likely lead to neurodegeneration. In vivo, we observed that cytoskeletal alterations, induced by a single injection of nocodazole, were sufficient to promote neurodegeneration of avulsed motoneurons. Besides, only pre-treatment with rapamycin, but not post-treatment, neuroprotected after nerve root avulsion. In agreement, overexpressing ATG5 in injured motoneurons led to neuroprotection and attenuation of cytoskeletal and trafficking-related abnormalities. These discoveries serve as proof of concept for autophagy-target therapy to halting the progression of neurodegenerative processes.

Organoselenium compounds prevent hyperphosphorylation of cytoskeletal proteins induced by the neurotoxic agent diphenyl ditelluride in cerebral cortex of young rats

International Nuclear Information System (INIS)

Moretto, M.B.; Funchal, C.; Zeni, G.; Rocha, J.B.T.; Pessoa-Pureur, R.

2005-01-01

In this work we investigated the protective ability of the selenium compounds ebselen and diphenyl diselenide against the effect of diphenyl ditelluride on the in vitro incorporation of 32 P into intermediate filament (IF) proteins from slices of cerebral cortex of 17-day-old rats. We observed that ditelluride in the concentrations of 1, 15 and 50 μM induced hyperphosphorylation of the high-salt Triton insoluble neurofilament subunits (NF-M and NF-L), glial fibrillary acidic protein (GFAP) and vimentin, without altering the immunocontent of these proteins. Concerning the selenium compounds, diselenide (1, 15 and 50 μM) did not induce alteration of the in vitro phosphorylation of the IF proteins. Otherwise, ebselen induced an altered in vitro phosphorylation of the cytoskeletal proteins in a dose-dependent manner. At intermediate concentrations (15 and 30 μM) it increased the in vitro phosphorylation even though, at low (5 μM) or high (50 and 100 μM) concentrations this compound was ineffective in altering the activity of the cytoskeletal-associated phosphorylating system. In addition, 15 μM diselenide and 5 μM ebselen, presented a protective effect against the action of ditelluride, on the phosphorylation of the proteins studied. Considering that hyperphosphorylation of cytoskeletal proteins is associated with neuronal dysfunction and neurodegeneration, it is probable that the effects of ditelluride could be related to the remarkable neurotoxicity of this organic form of tellurium. Furthermore the neuroprotective action of selenium compounds against tellurium effects could be a promising route to be exploited for a possible treatment of organic tellurium poisoning

Tumor affinity of technetium-99m labeled radiopharmaceuticals. II. Sup(99m)Tc-Sn-diphosphonate (sup(99m)Tc-EHDP), sup(99m)Tc-Sn-dimercaptosuccinic acid (sup(99m)Tc-DMSA), sup(99m)Tc-Sn-diethyl stilbestrol diphosphate (sup(99m)Tc-DSDP)

Energy Technology Data Exchange (ETDEWEB)

Itoh, K; Kobayashi, S; Hisada, K; Tonami, N [Kanazawa Univ. (Japan). School of Medicine; Ando, A

1976-10-01

The authors have examined the tumor affinity of various sup(99m)Tc-labelled radiopharmaceuticals to Ehrlich's tumor for the purpose of delineating human malignant neoplasm positively. The biologic distributions of sup(99m)Tc-Sn-diphosphonate (sup(99m)Tc-EHDP), sup(99m)Tc-Sn-dimercaptosuccinic acid (sup(99m)Tc-DMSA) and sup(99m)Tc-Sn-diethyl stilbestrol diphosphate (sup(99m)Tc-DSDP, sup(99m)Tc-Honvan) are included as the second report on the tumor affinity of Ehrlich-bearing mice. Tumor concentration of sup(99m)Tc-EHDP was lowest and the positive delineation of implanted tumor with sup(99m)Tc-EHDP was poorest in sequential images, though active accumulation in some soft tissues malignant neoplasms, breast cancer, and thyroid cancer, has been reported. Tumor concentration and the tumor-to-blood ratio of sup(99m)Tc-DMSA were not so high, contrary to our expectation that /sup 197/Hg-DMSA might show high tumor concentration and high tumor-to-blood ratio the same as /sup 197/Hg chlormerodrin of the renal scanning radiopharmaceuticals. Tumor concentration of sup(99m)Tc-DSDP was highest. The tumor-to-blood concentration ratio was lower than that of the above mentioned radiopharmaceuticals but the tumor-to-liver ratio and/or tumor-to-lung ratio was over 1.0 at the earlier time. Biologic distribution of sup(99m)Tc-DSDP was similar to that of /sup 32/P labeled DSDP. It is presumed that sup(99m)Tc is labeled at the phosphate ester of DSDP which is dephospholytated immediately by phospholylase in vivo following intravenous injection. Although it is not known precisely it may be assumed that the mechanism of accumulating sup(99m)Tc-DSDP in Ehrlich's tumor is related to the phospholylase activity in neoplasms.

Diversification of 99Mo/99mTc separation: non–fission reactor production of 99Mo as a strategy for enhancing 99mTc availability.

Science.gov (United States)

Pillai, Maroor R A; Dash, Ashutosh; Knapp, Furn F Russ

2015-01-01

This paper discusses the benefits of obtaining (99m)Tc from non-fission reactor-produced low-specific-activity (99)Mo. This scenario is based on establishing a diversified chain of facilities for the distribution of (99m)Tc separated from reactor-produced (99)Mo by (n,γ) activation of natural or enriched Mo. Such facilities have expected lower investments than required for the proposed chain of cyclotrons for the production of (99m)Tc. Facilities can receive and process reactor-irradiated Mo targets then used for extraction of (99m)Tc over a period of 2 wk, with 3 extractions on the same day. Estimates suggest that a center receiving 1.85 TBq (50 Ci) of (99)Mo once every 4 d can provide 1.48-3.33 TBq (40-90 Ci) of (99m)Tc daily. This model can use research reactors operating in the United States to supply current (99)Mo needs by applying natural (nat)Mo targets. (99)Mo production capacity can be enhanced by using (98)Mo-enriched targets. The proposed model reduces the loss of (99)Mo by decay and avoids proliferation as well as waste management issues associated with fission-produced (99)Mo.

Milk fat globule-epidermal growth factor-factor VIII-derived peptide MSP68 is a cytoskeletal immunomodulator of neutrophils that inhibits Rac1.

Science.gov (United States)

Hendricks, Louie; Aziz, Monowar; Yang, Weng-Lang; Nicastro, Jeffrey; Coppa, Gene F; Symons, Marc; Wang, Ping

2017-02-01

Prolonged neutrophil infiltration leads to exaggerated inflammation and tissue damage during sepsis. Neutrophil migration requires rearrangement of their cytoskeleton. Milk fat globule-epidermal growth factor-factor VIII-derived short peptide 68 (MSP68) has recently been shown to be beneficial in sepsis-induced tissue injury and mortality. We hypothesize that MSP68 inhibits neutrophil migration by modulating small GTPase Rac1-dependent cytoskeletal rearrangements. Bone marrow-derived neutrophils (BMDNs) or whole lung digest isolated neutrophils were isolated from 8 to 10 wk old C57BL/6 mice by Percoll density gradient centrifugation. The purity of BMDN was verified by flow cytometry with CD11b/Gr-1 staining. Neutrophils were stimulated with N-formylmethionine-leucine-phenylalanine (f-MLP) (10 nM) in the presence or absence of MSP68 at 10 nM or cecal ligation and puncture (CLP) was used to induce sepsis, and MSP68 was administered at 1 mg/kg intravenously. Cytoskeletal organization was assessed by phalloidin staining, followed by analysis using fluorescence microscopy. Activity of the Rac1 GTPase in f-MLP or CLP-activated BMDN in the presence or absence of MSP68 was assessed by GTPase enzyme-linked immunosorbent assay. Mitogen-activated protein (MAP) kinase activity was determined by western blot densitometry. BMDN treatment with f-MLP increased cytoskeletal remodeling as revealed by the localization of filamentous actin to the periphery of the neutrophil. By contrast, cells pretreated with MSP68 had considerably reduced filamentous actin polymerization. Cytoskeletal spreading is associated with the activation of the small GTPase Rac1. We found BMDN-treated with f-MLP or that were exposed to sepsis by CLP had increased Rac1 signaling, whereas the cells pretreated with MSP68 had significantly reduced Rac1 activation (P Rac1-MAP kinase-mediated neutrophil motility. Thus, MSP68 is a novel therapeutic candidate for regulating inflammation and tissue damage caused

Flame retardants in eggs of four gull species (Laridae) from breeding sites spanning Atlantic to Pacific Canada

International Nuclear Information System (INIS)

Chen Da; Letcher, Robert J.; Burgess, Neil M.; Champoux, Louise; Elliott, John E.; Hebert, Craig E.; Martin, Pamela; Wayland, Mark; Chip Weseloh, D.V.; Wilson, Laurie

2012-01-01

To compare legacy and emerging flame retardant (FR) contamination in Canadian marine and freshwater ecosystems, eggs of four gull species (Laridae) were collected from 26 colonies spanning Pacific to Atlantic Canada, including in the Great Lakes basin. Fourteen polybrominated diphenyl ether (PBDE) congeners and 20 non-PBDE FRs were analyzed, but BDE-47, -99, -100, -153, -154 and -209, hexabromocyclododecane (HBCD) and Dechlorane Plus (DP) syn- and anti-isomers were common, and where concentrations of ∑PBDEs (37–610 ng/g wet weight, ww) ≫ HBCD (0.5–12 ng/g ww) > ∑DP (not quantifiable-5.5 ng/g ww). All other FRs were generally not detectable. Stable nitrogen and carbon isotopes used as dietary tracers provided insights into the diet choice influences on the exposure sources and contamination patterns (e.g., PBDE congener compositions) for individual gulls from the same colony. Eggs from gulls breeding near metropolitan regions of higher human densities showed greater PBDE burdens than from other ecosystems. - Highlights: ► We investigated flame retardants in eggs of four gull species spanning Canada. ► Concentrations of ∑PBDE ≫ hexabromocyclododecane > ∑Dechlorane Plus in eggs. ► Stable nitrogen and carbon isotopes revealed diet sources of flame retardants. ► Human density near breeding sites influenced flame retardant burdens in eggs. - Various flame retardants were found in eggs of four gull species from sites across Canada, and levels were influenced by location, ecosystem, diet and proximity to human populations.

Status of Tc-99m and 99Mo/99mTc generator production in Bangladesh

International Nuclear Information System (INIS)

Abedin, Md. Zainul; Haque, Md. Azizul; Ali, Md. Ramjan; Hossain, Md. Anwar; Razzaque, Md. Abdur; Yasmin, Lyzu; Waheed, M. Fatima; Akhter, Rabeya; Mondal, Rafiuddin

2007-01-01

Radioisotope Production Division (RIPD) produced instant technetium-99m by solvent extraction method for several years. On R and D basis, the division produced portable sterile Tc-99m sublimation generator by irradiating titanium molybdate in the reactor. The division produced (4/batch) from imported fission Mo-99 till June 2005. Since August 2005, as per demand of the government hospitals, the division have been producing 12-14 pieces of 15 GBq chromatographic 99m Tc-generators weekly by using the new generator production plant installed last year having online Mo-99 loading system with the of producing 50 generator per batch. Development of PZC and (n,γ) 99 Mo based generator holds potential in Bangladesh. (author)

Pharmaceutical grade sodium (99mTc) pertechnetate from 99Mo/99mTc-TCM-Autosolex generator

International Nuclear Information System (INIS)

Chattopadhyay, Sankha; Barua, Luna; Das, Sujata Saha

2014-01-01

Technetium-99m (T 1/2 = 6.02h; 140.51 keV (89%)) is the most useful radioisotope in diagnostic nuclear medicine. More than 80% of all diagnostic procedures done worldwide in nuclear medicine centre are performed with 99m Tc. Worldwide crisis of fission 99 Mo based generator in recent past had put the nuclear medicine fraternity in very harsh situation. In order to have an indigenous solution of this problem, we tried to develop a computer controlled semi automated 99 Mo/ 99m Tc generator using MEK solvent extraction technique, which utilizes abundantly available 99 Mo produced by (n,γ) reaction in BARC reactors. The aim of this work is to provide a more reliable, computer controlled module (TCM- AUTOSOLEX) for the recovery of pharmaceutical grade 99m Tc from low specific activity 99 Mo based on solvent extraction methodology

[{sup 99m}Tc]TRODAT-1: a novel technetium-99m complex as a dopamine transporter imaging agent

Energy Technology Data Exchange (ETDEWEB)

Meiping, Kung [Department of Radiology, University of Pennsylvania, Philadelphia (United States); Stevenson, D A [Department of Radiology, University of Pennsylvania, Philadelphia (United States); Ploessl, K [Department of Radiology, University of Pennsylvania, Philadelphia (United States); Meegalla, S K [Department of Radiology, University of Pennsylvania, Philadelphia (United States); Beckwith, A [Department of Radiology, University of Pennsylvania, Philadelphia (United States); Essman, W D [Department of Psychiatry, University of Pennsylvania, Philadelphia (United States); Mu, M [Department of Radiology, University of Pennsylvania, Philadelphia (United States); Lucki, I [Department of Psychiatry, University of Pennsylvania, Philadelphia (United States); [Department of Pharmacology, University of Pennsylvania, Philadelphia (United States); Kung, H F [Department of Radiology, University of Pennsylvania, Philadelphia (United States); [Department of Pharmacology, University of Pennsylvania, Philadelphia (United States)

1997-04-01

Technetium-99m is the most commonly used radionuclide in routine nuclear medicine imaging procedures. Development of {sup 99m}Tc-labeled receptor-specific imaging agents for studying the central nervous system is potentially useful for evaluation of brain function in normal and disease states. A novel {sup 99m}Tc-labeled tropane derivative, [{sup 99m}Tc]TRODAT-1, which is useful as a potential CNS dopamine transporter imaging agent, was evaluated and characterized. After i.v. injection into rats, [{sup 99m}Tc]TRODAT-1 displayed specific brain uptake in the rat striatal region (striatum-cerebellum/cerebellum ratio 1.8 at 60 min), where dopamine neurons are concentrated. The specific striatal uptake could be blocked by pretreating rats with a dose of competing dopamine transporter ligand, {beta}-CIT (or RTI-55, i.v., 1 mg/kg). However, the specific striatal uptake of [{sup 99m}Tc]TRODAT-1 was not affected by co-injection of excess free ligand (TRODAT-1, up to 200 {mu}g per rat) or by pretreating the rats with haloperidol (i.v., 1 mg/kg). The specific uptake in striatal regions of rats that had prior 6-hydroxydopamine lesion in the substantia nigra area showed a dramatic reduction. The radioactive material recovered from the rat striatal homogenates at 60 min after i.v. injection of [{sup 99m}Tc]TRODAT-1 showed primarily the original compound (>95%), a good indication of in vivo stability in brain tissue. Similar and comparable organ distribution patterns and brain regional uptakes of [{sup 99m}Tc]TRODAT-1 were obtained for male and female rats. (orig./AJ). With 4 figs., 6 tabs.

Stress and strain in the contractile and cytoskeletal filaments of airway smooth muscle.

Science.gov (United States)

Deng, Linhong; Bosse, Ynuk; Brown, Nathan; Chin, Leslie Y M; Connolly, Sarah C; Fairbank, Nigel J; King, Greg G; Maksym, Geoffrey N; Paré, Peter D; Seow, Chun Y; Stephen, Newman L

2009-10-01

Stress and strain are omnipresent in the lung due to constant lung volume fluctuation associated with respiration, and they modulate the phenotype and function of all cells residing in the airways including the airway smooth muscle (ASM) cell. There is ample evidence that the ASM cell is very sensitive to its physical environment, and can alter its structure and/or function accordingly, resulting in either desired or undesired consequences. The forces that are either conferred to the ASM cell due to external stretching or generated inside the cell must be borne and transmitted inside the cytoskeleton (CSK). Thus, maintaining appropriate levels of stress and strain within the CSK is essential for maintaining normal function. Despite the importance, the mechanisms regulating/dysregulating ASM cytoskeletal filaments in response to stress and strain remained poorly understood until only recently. For example, it is now understood that ASM length and force are dynamically regulated, and both can adapt over a wide range of length, rendering ASM one of the most malleable living tissues. The malleability reflects the CSK's dynamic mechanical properties and plasticity, both of which strongly interact with the loading on the CSK, and all together ultimately determines airway narrowing in pathology. Here we review the latest advances in our understanding of stress and strain in ASM cells, including the organization of contractile and cytoskeletal filaments, range and adaptation of functional length, structural and functional changes of the cell in response to mechanical perturbation, ASM tone as a mediator of strain-induced responses, and the novel glassy dynamic behaviors of the CSK in relation to asthma pathophysiology.

Effective visualization of suppressed thyroid tissue by means of baseline 99mTc-methoxy isobutyl isonitrile in comparison with 99mTc-pertechnetate scintigraphy after TSH stimulation.

Science.gov (United States)

Vattimo, A; Bertelli, P; Burroni, L

1992-01-01

Baseline 99mTc-MIBI thyroid scintigraphy was compared with 99mTc-pertechnetate scintigraphy after TSH stimulation in seven patients with suppressed thyroid tissue due to an autonomously functioning thyroid nodule (AFTN). In all patients the suppressed thyroid tissue was visualized by means of both baseline 99mTc-MIBI and post-TSH 99mTc-pertechnetate scintigraphy, and in some cases the former technique provided better visualization. In one patient presenting a "warm" nodule T3-suppression did not affect the nodular/extranodular uptake ratio of 99mTc-MIBI, whereas the 99mTc-pertechnetate uptake ratio increased significantly. This leads us to hypothesize that the thyroid uptake of 99mTc-MIBI is not related to TSH control, but rather to other mechanisms such as the blood flow. Since exogenous TSH is no longer available, 99mTc-MIBI scintigraphy can be successfully used in the place of repeated 99mTc-pertechnetate scintigraphy after TSH stimulation in the assessment of AFTN.

Inhibition of phospholipase C disrupts cytoskeletal organization and gravitropic growth in Arabidopsis roots.

Science.gov (United States)

Andreeva, Zornitza; Barton, Deborah; Armour, William J; Li, Min Y; Liao, Li-Fen; McKellar, Heather L; Pethybridge, Kylie A; Marc, Jan

2010-10-01

The phospholipase protein superfamily plays an important role in hormonal signalling and cellular responses to environmental stimuli. There is also growing evidence for interactions between phospholipases and the cytoskeleton. In this report we used a pharmacological approach to investigate whether inhibiting a member of the phospholipase superfamily, phospholipase C (PLC), affects microtubules and actin microfilaments as well as root growth and morphology of Arabidopsis thaliana seedlings. Inhibiting PLC activity using the aminosteroid U73122 significantly inhibited root elongation and disrupted root morphology in a concentration-dependent manner, with the response being saturated at 5 μM, whereas the inactive analogue U73343 was ineffective. The primary root appeared to lose growth directionality accompanied by root waving and formation of curls. Immunolabelling of roots exposed to increasingly higher U73122 concentrations revealed that the normal transverse arrays of cortical microtubules in the elongation zone became progressively more disorganized or depolymerized, with the disorganization appearing within 1 h of incubation. Likewise, actin microfilament arrays also were disrupted. Inhibiting PLC using an alternative inhibitor, neomycin, caused similar disruptions to both cytoskeletal organization and root morphology. In seedlings gravistimulated by rotating the culture plates by 90°, both U73122 and neomycin disrupted the normal gravitropic growth of roots and etiolated hypocotyls. The effects of PLC inhibitors are therefore consistent with the notion that, as with phospholipases A and D, PLC likewise interacts with the cytoskeleton, alters growth morphology, and is involved in gravitropism.

Body burdens of polybrominated diphenyl ethers among urban anglers.

Science.gov (United States)

Morland, Kimberly B; Landrigan, Philip J; Sjödin, Andreas; Gobeille, Alayne K; Jones, Richard S; McGahee, Ernest E; Needham, Larry L; Patterson, Donald G

2005-12-01

Polybrominated diphenyl ethers (PBDEs) have been widely used in the United States and worldwide as flame retardants. Recent PBDE production figures show that worldwide use has increased. To determine whether fish consumption is a source of PBDE exposure for humans, a cross-sectional epidemiologic study of New York and New Jersey urban anglers was conducted during the summers of 2001-2003. Frequency of local fish consumption was assessed by questionnaire, and blood samples for PBDE analysis were collected from 94 anglers fishing from piers on the lower Hudson River and Newark Bay. We analyzed PBDEs by gas chromatography-isotope dilution-high-resolution mass spectrometry. The congeners found in anglers' serum at the highest concentrations were, by International Union of Pure and Applied Chemistry numbers, BDE-47, BDE-153, and BDE-99. Anglers reporting consumption of local fish had higher, but nonstatistically significantly different, concentrations of PBDEs than did anglers who did not eat local fish. For some congeners (BDE-100 and BDE-153), we observed moderate dose-response relationships between serum PBDE levels and frequency of reported fish intake. These findings suggest that consumption of locally caught fish is not a major route of human exposure for this study population.

Airborne concentrations of Polybrominated diethyl etherin residential homes

Directory of Open Access Journals (Sweden)

S. Rahimzadeh

2009-07-01

Full Text Available Background and aims   Polybrominated diphenyl ethers (PBDE have been widely applied to different home and offices' appliances as flame retardant additives to inhibit ignition and enhance  the fire safety. Their toxicity, health effects, and resistance to environmental degradation are  matters of great interested among scientists. Airborne concentrations of PBDE in residential  homes were determined in this study.   Methods   In a cross sectional study, 33 residential homes were selected and airborne concentrations of PBDEs were investigated using PUF disk passive air samplers. Also in two building the concentraction of PBDEs were monitored in two rooms of a department in each building for 12 months.   Results   Average airborne concentration of ?PBDE (sum of congener #s 17, 28, 47, 49, 66, 85, 99, 100, 153, and 154 for all locations monitored was 52 (4-245 pgm -3 . While in one of the buildings the contaminant level of bedroom was significantly higher than the living room, PBDE   concentrations remained relatively constant for whole monitoring period.   Conclusion   The range of concentrations results to a wide variation between inhalation intakes of dwellers of the lowest and the highest contaminated homes (~50 folds.  

Evidence of immunomodulation in nestling American kestrels (Falco sparverius) exposed to environmentally relevant PBDEs

Energy Technology Data Exchange (ETDEWEB)

Fernie, Kim J. [Canadian Wildlife Service, PO Box 5050, 867 Lakeshore Rd., Burlington, Ontario, L7R 4A6 (Canada)]. E-mail: kim.fernie@ec.gc.ca; Mayne, Greg [Canadian Wildlife Service, PO Box 5050, 867 Lakeshore Rd., Burlington, Ontario, L7R 4A6 (Canada); Shutt, J. Laird [National Wildlife Research Centre, Canadian Wildlife Service, 1125 Colonel By Drive, Ottawa, Ontario, K1S 5B6 (Canada); Pekarik, Cynthia [Canadian Wildlife Service, PO Box 5050, 867 Lakeshore Rd., Burlington, Ontario, L7R 4A6 (Canada); Grasman, Keith A. [Department of Biological Sciences, Wright State University, 3640 Colonel Glenn Highway, Dayton, OH 45435 (United States); Letcher, Robert J. [National Wildlife Research Centre, Canadian Wildlife Service, 1125 Colonel By Drive, Ottawa, Ontario, K1S 5B6 (Canada); Great Lakes Institute for Environmental Research, University of Windsor, 401 Sunset Avenue, Windsor, Ontario, N9B 3P4 (Canada); Drouillard, Ken [Great Lakes Institute for Environmental Research, University of Windsor, 401 Sunset Avenue, Windsor, Ontario, N9B 3P4 (Canada)

2005-12-15

We investigated whether exposure to environmentally relevant polybrominated diphenyl ethers (PBDEs) causes immunomodulation in captive nestling American kestrels (Falco sparverius). Eggs within each clutch, divided by laying sequence, were injected with safflower oil or penta-BDE congeners-47, -99, -100, and -153 dissolved in safflower oil (18.7 {mu}g {sigma}PBDEs/egg) approximating Great Lakes birds. For 29 days, nestlings consumed the same PBDE mixture (15.6{+-}0.3 ng/g body weight per day), reaching {sigma}PBDE body burden concentrations that were 120x higher in the treatment birds (86.1{+-}29.1 ng/g ww) than controls (0.73{+-}0.5 ng/g ww). PBDE-exposed birds had a greater PHA response (T-cell-mediated immunity), which was negatively associated with increasing BDE-47 concentrations, but a reduced antibody-mediated response that was positively associated with increasing BDE-183 concentrations. There were also structural changes in the spleen (fewer germinal centers), bursa (reduced apoptosis) and thymus (increased macrophages), and negative associations between the spleen somatic index and {sigma}PBDEs, and the bursa somatic index and BDE-47. Immunomodulation from PBDE exposure may be exacerbated in wild birds experiencing greater environmental stresses. - Exposure to environmentally relevant polybrominated diphenyl ethers (congeners and concentrations) resulted in the immunomodulation of nestling American kestrels.

Evidence of immunomodulation in nestling American kestrels (Falco sparverius) exposed to environmentally relevant PBDEs

International Nuclear Information System (INIS)

Fernie, Kim J.; Mayne, Greg; Shutt, J. Laird; Pekarik, Cynthia; Grasman, Keith A.; Letcher, Robert J.; Drouillard, Ken

2005-01-01

We investigated whether exposure to environmentally relevant polybrominated diphenyl ethers (PBDEs) causes immunomodulation in captive nestling American kestrels (Falco sparverius). Eggs within each clutch, divided by laying sequence, were injected with safflower oil or penta-BDE congeners-47, -99, -100, and -153 dissolved in safflower oil (18.7 μg ΣPBDEs/egg) approximating Great Lakes birds. For 29 days, nestlings consumed the same PBDE mixture (15.6±0.3 ng/g body weight per day), reaching ΣPBDE body burden concentrations that were 120x higher in the treatment birds (86.1±29.1 ng/g ww) than controls (0.73±0.5 ng/g ww). PBDE-exposed birds had a greater PHA response (T-cell-mediated immunity), which was negatively associated with increasing BDE-47 concentrations, but a reduced antibody-mediated response that was positively associated with increasing BDE-183 concentrations. There were also structural changes in the spleen (fewer germinal centers), bursa (reduced apoptosis) and thymus (increased macrophages), and negative associations between the spleen somatic index and ΣPBDEs, and the bursa somatic index and BDE-47. Immunomodulation from PBDE exposure may be exacerbated in wild birds experiencing greater environmental stresses. - Exposure to environmentally relevant polybrominated diphenyl ethers (congeners and concentrations) resulted in the immunomodulation of nestling American kestrels

Accuracy of 99Molybdenum assays in /sup 99m/Technetium solutions

International Nuclear Information System (INIS)

Williams, C.C.; Kereiakes, J.G.; Grossman, L.W.

1981-01-01

A study was performed to determine the accuracy of 99 Mo measurements using three commercial dose calibrators with their 99 Mo assay shields. One 99 Mo assay shield allowed excessive penetration by the lower energy /sup 99m/Tc photons, resulting in the calibrator's falsely high interpretation of the activity of 99 Mo present in the high-activity /sup 99m/Tc eluates. All three calibrators performed adequately with a National Bureau of Standards 99 Mo standard in equilibrium with /sup 99m/Tc. By using low-activity aliquots of 99 Mo and /sup 99m/Tc, a low-level linearity test was performed. Only one of the calibrators was found to reflect accurately the activity of 99 Mo present under all conditions tested

Plasma concentrations of persistent organic pollutants in the Cree of northern Quebec, Canada: results from the multi-community environment-and-health study.

Science.gov (United States)

Liberda, Eric N; Tsuji, Leonard J S; Martin, Ian D; Cote, Suzanne; Ayotte, Pierre; Dewailly, Eric; Nieboer, Evert

2014-02-01

Historically, resource development has had negative impacts on the traditional lifestyle of First Nation Cree Communities in the Province of Quebec, Canada. In response to the perceived need for fisheries restoration and for managing health concerns associated with environmental pollutants, the Mercury Program in the James Bay Region of Quebec was reconstituted in 2001 and broadened to include a wider range of chemicals of concern. Based on comprehensive surveys of the nine Cree Territory (Eeyou Istchee) communities in this region during the period 2002-2009, blood plasma concentrations are presented of Aroclor 1260, PCB congeners 28, 52, 99, 101, 105, 118, 128, 138, 153, 156, 163, 170, 180, 183, and 187, Aldrin, ß-HCH, α-Chlordane, γ-Chlordane, oxy-Chlordane, trans-Nonachlor, cis-Nonachlor, p,p'-DDT, p,p'-DDE, Hexachloro benzene (HCB), Mirex, PBB 153, PBDE 47, PBDE 99, PBDE 100, PBDE 153, Toxaphene 26, and Toxaphene 50. The organohalogenated compounds were extracted using solid-phase extraction and cleaned on florisil columns before high resolution HRGC-MS analysis. Principal component analysis (PCA) was used to reduce the large number of contaminant variables into a smaller number of uncorrelated variables. ANOVA identified significant differences between age groups, with the older participants having higher body burdens of legacy lipophilic contaminants, but not for the PBDEs. In certain female age groups, plasma concentrations of PBDEs were observed to be lower than for males; conversely, DDT was higher. Among communities, concentrations were different (p<0.001) for all contaminants. This work provides a baseline for the James Bay Eeyou Istchee communities who, to varying degrees, rely on food and other resources from the land and therefore are at higher risk of increased body burdens of legacy persistent organic pollutants (POPs). © 2013.

Study of methodologies for quality control of 99Mo used in 99Mo/99mTc generators

International Nuclear Information System (INIS)

Said, Daphne de Souza

2016-01-01

99m Tc is the most used radionuclide in nuclear medicine. In Brazil, the 99 Mo/ 99m Tc generators are exclusively produced by Radiopharmacy Center at IPEN-CNEN/ SP, by importing 99 Mo from different suppliers. 99 Mo (t 1/2 = 66 h) is a fission product of 235 U and it can have radionuclidic impurities that are prejudicial for human health. For safe use of generators, it is necessary to perform the evaluation of 99 Mo by quality control tests in order to assess if 99 Mo complies with the specifications. The European Pharmacopoeia (EP) presents a monograph for evaluation of the quality of the [ 99 Mo] solution as sodium molybdate,that is used as raw material for 99 Mo/ 99m Tc generators production, including specification parameters (identification, radiochemical purity and radionuclidic purity), analysis methods and limits. However, it has been observed difficulties on the execution and implementation of these methods by the generators producers, with a few literature about this subject, probably due to complexity of the proposed methods. In this work, many quality control parameters of 99 Mo described in the EP monograph were evaluated. Separation methods for 99M o from its radionuclidic impurities by solid phase extraction (SPE) and TLC were studied. After SPE separation, the quantification of metals by ICP-OES to evaluate the percentage of retention of Mo and the percentage of recovery of Ru, Te and Sr using different types of cartridges were proposed, replacing radiotracers use. It was observed that the specific type of SPE cartridge recommended by the EP for separation of 99 Mo presented low recoveries for Ru, compared to other available anion exchange SPE cartridges. 99 Mo samples from different worldwide suppliers were analyzed. It was observed that quantification of 103 Ru in 99 Mo samples with decay time higher than 4 weeks is possible. An alternative method for separation of 131 I from 99 Mo showed promising results by TLC. The quantification of beta and

Current status of production and supply of molybdenum-99 and 99Mo/99mTc generators in Indonesia

International Nuclear Information System (INIS)

Mutalib, A.

2003-01-01

Production of high-specific activity molybdenum-99 and 99 Mo/ 99m Tc Generators in Indonesia commenced when a new production facility supported by the presence of a 30 MW multipurpose reactor (RSG-GAS) was established in Serpong in 1990. This report describes the current production and supply of molybdenum-99m devoted mainly to fulfill the domestic demands in supplying 99 Mo/ 99m Tc Generators. Recent development on the use of LEU (Low Enriched Uranium) targets for replacing current HEU (High Enriched Uranium) targets in the production of 99 Mo will be reviewed briefly. (author)

Measurement of Mo-99 column activity in the evaluation of Mo-99/Tc-99m generator

International Nuclear Information System (INIS)

Kuster, Z.

1994-01-01

In order to calculate the real elution efficiency of Mo-99/Tc-99m generator the Mo-99 content on the column has to be previously determined. As found in this work, the external measurement of Mo-99-column activity by means of Geiger-Mueller counter is a simple, fast and reliable method. Generally, Mo-99-column is placed slightly out of the center of the generator; therefore the externally measured flux of photons (φ) is an angular-dependent function. If the thickness of the lead container is radially uniform, the flux measured at some distance from the generator (which is rotated in 2π/3 steps) is given by the equation φ = A (1 + Bcos (α-2π(i - 2)/3)) -1 , i=1,2 or 3 (Eq.1) where A is a numerical constant depending on the Mo-99-column activity, B is a numerical constant depending on the Mo-99- column position within the lead container, the angle α depends on the initial orientation of the generator. A total of 20 generator were studied. The measured Mo-99-column activities (Capintec dose calibrator) were in the range 13.1- 35.11 GBq. Contrary to the findings of Vinberg and Kristensen (Eur J Nucl Med 1/1976(219), values of A (Eq. 1) are in good correlation (r 2 =0.9794) with the measured Mo-99-column activities. (author)

Cytoskeletal actin genes function downstream of HNF-3beta in ascidian notochord development.

Science.gov (United States)

Jeffery, W R; Ewing, N; Machula, J; Olsen, C L; Swalla, B J

1998-11-01

We have examined the expression and regulation of cytoskeletal actin genes in ascidians with tailed (Molgula oculata) and tailless larvae (Molgula occulta). Four cDNA clones were isolated representing two pairs of orthologous cytoskeletal actin genes (CA1 and CA2), which encode proteins differing by five amino acids in the tailed and tailless species. The CA1 and CA2 genes are present in one or two copies, although several related genes may also be present in both species. Maternal CA1 and CA2 mRNA is present in small oocytes but transcript levels later decline, suggesting a role in early oogenesis. In the tailed species, embryonic CA1 and CA2 mRNAs first appear in the presumptive mesenchyme and muscle cells during gastrulation, subsequently accumulate in the presumptive notochord cells, and can be detected in these tissues through the tadpole stage. CA1 mRNAs accumulate initially in the same tissues in the tailless species but subsequently disappear, in concert with the arrest of notochord and tail development. In contrast, CA2 mRNAs were not detected in embryos of the tailless species. Fertilization of eggs of the tailless species with sperm of the tailed species, which restores the notochord and the tail, also results in the upregulation of CA1 and CA2 gene expression in hybrid embryos. Antisense oligodeoxynucleotide experiments suggest that CA1 and CA2 expression in the notochord, but not in the muscle cells, is dependent on prior expression of Mocc FHI, an ascidian HNF-3beta-like gene. The expression of the CA1 and CA2 genes in the notochord in the tailed species, downregulation in the tailless species, upregulation in interspecific hybrids, and dependence on HNF-3beta activity is consistent with a role of these genes in development of the ascidian notochord.

Polybrominated diphenyl ether congeners in the young-of-the-year bluefish, Pomatomus saltatrix, from several nursery habitats along the US Atlantic coastline.

Science.gov (United States)

Deshpande, Ashok D; Dockum, Bruce W

2013-12-15

Spatial trends of polybrominated diphenyl ether (PBDE) congeners were examined by using high resolution gas chromatography-low resolution electron impact mass spectrometry (GC-EIMS) in 414 samples of young-of-the-year (YOY) bluefish (Pomatomus saltatrix) collected from a total of 29 nursery habitats along the US Atlantic coastline from Massachusetts to Florida. Of the 26 target PBDE congeners, BDE-47 (4 Br), BDE-100 (5 Br), BDE-49 (4 Br), BDE-99 (5 Br), and BDE-154 (6 Br) were the five most frequently detected congeners in the order of decreasing importance. The sum of the concentrations of five major PBDE congeners, referred to as ΣPBDEs, varied between estuaries and also among samples from a given estuary. ΣPBDEs were lowest in YOY bluefish from Vineyard Sound, Nantucket Sound, Great Bay, Delaware Bay, Lynnhaven Bay, Cape Lookout, and Crescent Beach, with maximum ΣPBDE concentrations below 10 ng/g wet weight. ΣPBDEs in three bluefish samples from Stamford Harbor were detected at relatively high to unusually high concentrations of 69.1, 205, and 561 ng/g wet weight. ΣPBDE values for other Stamford Harbor bluefish were generally low. Highest PBDE concentrations were detected in the vicinity of industrial and urban locations within the New York-New Jersey metropolitan complex. Among them, bluefish from Newark Bay were generally the most contaminated with an average ΣPBDE value of 56.6 ± 30.8 ng/g wet weight. ΣPBDEs in bluefish from Newark Bay were numerically greater than ΣPBDEs in bluefish from all locations, however these differences were not statistically significant. Modest to good correlations between ΣPBDEs and lipids were observed for YOY bluefish from Buzzards Bay, Upper New Bedford Harbor, Lower New Bedford Harbor, Outer New Bedford Harbor, Providence Harbor, Housatonic River, Norwalk Harbor, Little Neck Bay, Newark Bay, Sandy Hook Bay, Great Bay, Delaware Bay, Patuxent River and Crescent Beach. Poor correlations between ΣPBDE and lipids were

Quality assurance of Mo-99/Tc-99m radionuclide generators

Science.gov (United States)

Uzunov, Nikolay; Yordanova, Galina; Salim, Seniha; Stancheva, Natalya; Mineva, Vanya; Meléndez-Alafort, Laura; Rosato, Antonio

2018-03-01

Gamma-ray spectrometry analyses of the radionuclide content of eluate from two Mo-99/Tc-99m radionuclide generators POLTECHNET have been performed. The relative activities of 99Mo 103Ru and 131I radioisotopes with respect to the activity of 99mTc at different time intervals after the primary pertechnetate elution of the generators have been analyzed. The relative activities of the isotopes were determined and compared to the radionuclidic purity requirements for 99mTc.

Estradiol influences the mechanical properties of human fetal osteoblasts through cytoskeletal changes

Energy Technology Data Exchange (ETDEWEB)

Muthukumaran, Padmalosini [Department of Bioengineering, National University of Singapore (Singapore); Lim, Chwee Teck [Department of Bioengineering, National University of Singapore (Singapore); Department of Mechanical Engineering, National University of Singapore (Singapore); Mechanobiology Institute, National University of Singapore (Singapore); Singapore-MIT Alliance for Research and Technology (SMART), National University of Singapore (Singapore); Lee, Taeyong, E-mail: bielt@nus.edu.sg [Department of Bioengineering, National University of Singapore (Singapore)

2012-07-06

Highlights: Black-Right-Pointing-Pointer Estradiol induced stiffness changes of osteoblasts were quantified using AFM. Black-Right-Pointing-Pointer Estradiol causes significant decrease in the stiffness of osteoblasts. Black-Right-Pointing-Pointer Decreased stiffness was caused by decreased density of f-actin network. Black-Right-Pointing-Pointer Stiffness changes were not associated with mineralized matrix of osteoblasts. Black-Right-Pointing-Pointer Estradiol increases inherent alkaline phosphatase activity of osteoblasts. -- Abstract: Estrogen is known to have a direct effect on bone forming osteoblasts and bone resorbing osteoclasts. The cellular and molecular effects of estrogen on osteoblasts and osteoblasts-like cells have been extensively studied. However, the effect of estrogen on the mechanical property of osteoblasts has not been studied yet. It is important since mechanical property of the mechanosensory osteoblasts could be pivotal to its functionality in bone remodeling. This is the first study aimed to assess the direct effect of estradiol on the apparent elastic modulus (E{sup Asterisk-Operator }) and corresponding cytoskeletal changes of human fetal osteoblasts (hFOB 1.19). The cells were cultured in either medium alone or medium supplemented with {beta}-estradiol and then subjected to Atomic Force Microscopy indentation (AFM) to determine E{sup Asterisk-Operator }. The underlying changes in cytoskeleton were studied by staining the cells with TRITC-Phalloidin. Following estradiol treatment, the cells were also tested for proliferation, alkaline phosphatase activity and mineralization. With estradiol treatment, E{sup Asterisk-Operator} of osteoblasts significantly decreased by 43-46%. The confocal images showed that the changes in f-actin network observed in estradiol treated cells can give rise to the changes in the stiffness of the cells. Estradiol also increases the inherent alkaline phosphatase activity of the cells. Estradiol induced stiffness

Estradiol influences the mechanical properties of human fetal osteoblasts through cytoskeletal changes

International Nuclear Information System (INIS)

Muthukumaran, Padmalosini; Lim, Chwee Teck; Lee, Taeyong

2012-01-01

Highlights: ► Estradiol induced stiffness changes of osteoblasts were quantified using AFM. ► Estradiol causes significant decrease in the stiffness of osteoblasts. ► Decreased stiffness was caused by decreased density of f-actin network. ► Stiffness changes were not associated with mineralized matrix of osteoblasts. ► Estradiol increases inherent alkaline phosphatase activity of osteoblasts. -- Abstract: Estrogen is known to have a direct effect on bone forming osteoblasts and bone resorbing osteoclasts. The cellular and molecular effects of estrogen on osteoblasts and osteoblasts-like cells have been extensively studied. However, the effect of estrogen on the mechanical property of osteoblasts has not been studied yet. It is important since mechanical property of the mechanosensory osteoblasts could be pivotal to its functionality in bone remodeling. This is the first study aimed to assess the direct effect of estradiol on the apparent elastic modulus (E ∗ ) and corresponding cytoskeletal changes of human fetal osteoblasts (hFOB 1.19). The cells were cultured in either medium alone or medium supplemented with β-estradiol and then subjected to Atomic Force Microscopy indentation (AFM) to determine E ∗ . The underlying changes in cytoskeleton were studied by staining the cells with TRITC-Phalloidin. Following estradiol treatment, the cells were also tested for proliferation, alkaline phosphatase activity and mineralization. With estradiol treatment, E ∗ of osteoblasts significantly decreased by 43–46%. The confocal images showed that the changes in f-actin network observed in estradiol treated cells can give rise to the changes in the stiffness of the cells. Estradiol also increases the inherent alkaline phosphatase activity of the cells. Estradiol induced stiffness changes of osteoblasts were not associated with changes in the synthesized mineralized matrix of the cells. Thus, a decrease in osteoblast stiffness with estrogen treatment was

Validation of an ergonomic method to withdraw [99mTc] radiopharmaceuticals.

Science.gov (United States)

Blondeel-Gomes, Sandy; Marie, Solène; Fouque, Julien; Loyeau, Sabrina; Madar, Olivier; Lokiec, François

2017-11-10

The main objective of the present work was to ensure quality of radiopharmaceuticals syringes withdrawn with a "Spinal needle/obturator In-Stopper" system. Methods: Visual examinations and physicochemical tests are performed at T0 and T+4h for [ 99m Tc]albumin nanocolloid and T+7h for [ 99m Tc]eluate, [ 99m Tc] HydroxyMethylene DiPhosphonate and [ 99m Tc]Human Serum Albumin. Microbiological validation was performed according to European pharmacopoeia. Fingertip radiation exposure was evaluated to confirm the safety of the system. Results: Results show stable visual and physicochemical properties. The integrity of the connector was not affected after 30 punctures (no cores). No microbiological contamination was found on tested syringes. Conclusion: The system could be used 30 times. The stability of syringes drawing with this method is guaranteed up to 4 hours for [ 99m Tc]albumin nanocolloid and 7 hours for [ 99m Tc]eluate, [ 99m Tc]HydroxyMethylene DisPhosphonate and [ 99m Tc]Human serum albumin. Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Polybrominated diphenyl ethers (PBDEs) in feathers of colonial water-bird species from Pakistan

Energy Technology Data Exchange (ETDEWEB)

Malik, Riffat Naseem, E-mail: r_n_malik2000@yahoo.co.uk [Environmental Biology Laboratory, Department of Plant Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, PO 45320 (Pakistan); Moeckel, Claudia [Centre for Ecology and Hydrology, Lancaster Environment Centre, Library Avenue, Bailrigg, Lancaster LA1 4AP (United Kingdom); Jones, Kevin C.; Hughes, David [Centre for Chemicals Management, Lancaster Environment Centre, Lancaster University, Bailrigg, Lancaster LA1 4YQ (United Kingdom)

2011-10-15

Feathers of two colonial water-birds species (Bubulcus ibis, Egretta garzetta) from four heronries in the Punjab province, Pakistan were analysed for 28 Polybrominated Diphenyl Ethers (PBDEs) congeners. Median concentrations of {Sigma}PBDEs were 2.41 and 1.91 ng/g in little and cattle egrets. PBDE-47, -100, -138, -153 were abundant and detected in >70% of feather samples in both species. Species-specific differences based on dietary preferences indicated higher concentration of PBDE-47, -66, -75, -100, -153, -154, and -183 in fish eating little egret. BDE-47 and -100 were more frequent in little egrets and BDE-99 was more dominant in cattle egret which feed on terrestrial habitat. Higher {Sigma}hexa- and hepta-BDEs congeners showed larger concentrations in feathers from heronries close to water bodies which receive urban and industrial effluents whereas lower-brominated congeners (BDE-47-BDE-100) dominated in rural/agricultural regions. Hazard quotients (HQs) indicated that measured {Sigma}PBDEs pose no risk to egret population. - Highlights: > Feathers as non-destructive tool to asses Polybrominated Diphenyl Ethers (PBDEs) contamination. > PBDE-47 and -100 frequent in feathers of fish eating egrets. > BDE-99 dominant in feathers of egrets feed in terrestrial habitats. > Lower-brominated congeners (BDE-47-BDE-100) dominate in feathers from rural areas. > Greater contents of hexa- and hepta-BDEs in feathers from areas receive urban/industrial effluents. - Feathers are used as a biomonitoring tool for PBDEs contamination.

Polybrominated diphenyl ethers (PBDEs) in feathers of colonial water-bird species from Pakistan

International Nuclear Information System (INIS)

Malik, Riffat Naseem; Moeckel, Claudia; Jones, Kevin C.; Hughes, David

2011-01-01

Feathers of two colonial water-birds species (Bubulcus ibis, Egretta garzetta) from four heronries in the Punjab province, Pakistan were analysed for 28 Polybrominated Diphenyl Ethers (PBDEs) congeners. Median concentrations of ΣPBDEs were 2.41 and 1.91 ng/g in little and cattle egrets. PBDE-47, -100, -138, -153 were abundant and detected in >70% of feather samples in both species. Species-specific differences based on dietary preferences indicated higher concentration of PBDE-47, -66, -75, -100, -153, -154, and -183 in fish eating little egret. BDE-47 and -100 were more frequent in little egrets and BDE-99 was more dominant in cattle egret which feed on terrestrial habitat. Higher Σhexa- and hepta-BDEs congeners showed larger concentrations in feathers from heronries close to water bodies which receive urban and industrial effluents whereas lower-brominated congeners (BDE-47-BDE-100) dominated in rural/agricultural regions. Hazard quotients (HQs) indicated that measured ΣPBDEs pose no risk to egret population. - Highlights: → Feathers as non-destructive tool to asses Polybrominated Diphenyl Ethers (PBDEs) contamination. → PBDE-47 and -100 frequent in feathers of fish eating egrets. → BDE-99 dominant in feathers of egrets feed in terrestrial habitats. → Lower-brominated congeners (BDE-47-BDE-100) dominate in feathers from rural areas. → Greater contents of hexa- and hepta-BDEs in feathers from areas receive urban/industrial effluents. - Feathers are used as a biomonitoring tool for PBDEs contamination.

Molybdenum-99/technetium-99M generators

International Nuclear Information System (INIS)

Morcos, N.A.; Bruno, G.A.; Haney, T.A.

1981-01-01

A 99 Mo/sup(99m)Tc generator is described which has an alumina support medium consisting of multiple beds of controlled pH and in which no bed has a pH value higher than the bed preceding it. It is claimed that by using this method low yield problems of such generators can be mitigated. (U.K.)

Generators of 99Mo-99mTc

International Nuclear Information System (INIS)

Robles, A.M.

1994-01-01

Between the radioisotopes family pairs we find the 99 Molibdenum - 99m technetium pairs. Such as isotope production,decay and chemical toxic, humid and dry generators,radiation protection handling practice and blinding had been sudied in this work.Tabs

Development of 99Mo/99mTc Generator System for Production of Medical Radionuclide 99mTc using a Neutron-activated 99Mo and Zirconium Based Material (ZBM as its Adsorbent

Directory of Open Access Journals (Sweden)

I. Saptiama

2016-12-01

Full Text Available Molybdenum produced from fission of U-235 is the most desirable precursor for 99Mo/99mTc generator system as it is non-carrier added and has high specific activity. However, in the last decade there has been short supply of 99Mo due to several constrains. Therefore, there have been many works performed for development of 99Mo/99mTc generator system using 99Mo which is not produced from either LEU or HEU. This report deals with development of 99Mo/99mTc generator system where zirconium-based material (ZBM is used as adsorbent of neutron-activated 99Mo. The system was prepared by firstly irradiating natural Mo in the G. A. Siwabessy reactor to produce neutron-activated 99Mo. The target was dissolved in NaOH 4N and then neutralized with 12 M HCl. The 99Mo solution was then mixed with a certain amount of ZBM followed by heating at 90°C for three hours to allow the 99Mo adsorbed on ZBM. The 99Mo-ZBM (9.36 GBq of 99Mo was Mo/ 4.2 g ZBM was packed on a fritz-glass column. This column was then fitted serially with an alumina column for trapping 99Mo breakthrough. The columns were then eluted daily with saline solution for up to one week. The yield of 99mTc was found to be between 53.7 – 74% (n= 5. All 99mTc eluates were clear solutions with pH of 5. Breakthrough of 99Mo in 99mTc eluates was found to be 0.031 ± 0.019 μCi 99Mo/ mCi 99mTc (n= 5 which was less than the maximum activity of 99Mo allowed in 99mTc solution ( 99%. Radiolabeling of this 99mTc towards methylene diphosphonate (MDP kit gave a radiolabelling efficiency of 99%. In summary, a new 99Mo/99mTc generator system that used neutron-activated 99Mo and ZBM as its adsorbent has been successfully prepared. The 99mTc produced from this new 99Mo/99mTc generator system attained the quality of 99mTc required for medical purposes.

Concentrations and speciation of polybrominated diphenyl ethers in human amniotic fluid

Science.gov (United States)

Miller, Mark F.; Chernyak, Sergei M.; Domino, Steven E.; Batterman, Stuart A.; Loch-Caruso, Rita

2012-01-01

Polybrominated diphenyl ethers (PBDEs) are persistent organic chemicals used as flame retardants in textiles, plastics, and consumer products. Although PBDE accumulation in humans has been noted since the 1970s, few studies have investigated PBDEs within the gestational compartment, and none to date has identified levels in amniotic fluid. The present study reports congener-specific brominated diphenyl ether (BDE) concentrations in second-trimester clinical amniotic fluid samples collected in 2009 from fifteen women in southeast Michigan, USA. Twenty-one BDE congeners were measured by GC/MS/NCI. The average total PBDE concentration was 3795 pg/ml amniotic fluid (range: 337 – 21842 pg/ml). BDE-47 and BDE-99 were identified in all samples. Based on median concentrations, the dominant congeners were BDE-208, 209, 203, 206, 207, and 47 representing 23, 16, 12, 10, 9 and 6%, respectively, of the total detected PBDEs. PBDE concentrations were identified in all amniotic fluid samples from southeast Michigan, supporting a need for further investigations of fetal exposure pathways and potential impacts on perinatal health. PMID:22236635

The new 99mTc myocardial perfusion imaging agents: 99mTc-sestamibi and 99mTc-teboroxime

International Nuclear Information System (INIS)

Berman, D.S.; Kiat, H.; Maddahi, J.

1991-01-01

The two new 99m (99mTc) labeled myocardial perfusion agents, 99mTc-Sestamibi and 99mTc-Teboroxime, are now available for routine clinical application. Both agents allow assessment of ejection fraction by the first-pass technique at rest or during exercise, thus providing additional information not available with thallium-201. 99mTc-Sestamibi has long myocardial residence time, as well as adequate myocardial extraction, providing images of higher count density and superior quality compared with thallium-201. 99mTc-Teboroxime has excellent myocardial uptake characteristics but is cleared very rapidly from the myocardium. Both tracers have shown results similar to those obtained with thallium-201 for detection of coronary artery disease and the assessment of defect reversibility. 99mTc-Sestamibi studies using the rest/stress imaging sequence can be accomplished in approximately 5 hours; studies using dual-isotope imaging (rest thallium-201 and stress 99mTc-Sestamibi injection) can be completed in 1 to 2 hours. Gated stress images can be performed with 99mTc-Sestamibi, providing simultaneous information of myocardial perfusion at stress and resting wall motion or thickening and allowing rapid differentiation of ischemic from infarcted tissue. Because of its slow myocardial clearance and absence of redistribution, 99mTc-Sestamibi allows uncoupling of the time of injection from the time of imaging and thus can be valuable in the evaluation of acute myocardial infarction and outcome of thrombolytic therapy. With 99mTc-Teboroxime, rapid serial studies are feasible. Pharmacologic stress and rest studies with 99mTc-Teboroxime single photon emission computed tomography potentially can be completed in under 30 minutes. 73 references

Polybrominated diphenyl ethers: human tissue levels and toxicology.

Science.gov (United States)

Gill, Udai; Chu, Ih; Ryan, John J; Feeley, Mark

2004-01-01

PBDEs are being released to the environment in wastes from their production facilities, degradation, or leaching and volatilization from products that contain PBDEs during the product's useful life. Brominated diphenyl ether congeners BDE-47, -99, and -153 are ubiquitous in the environment and are regarded as the most dominant congeners present in wildlife and humans. The tetra- to hexa-BDE are most likely the congeners to which humans are exposed through food consumption. Knowledge of PBDE uptake, metabolism, elimination, and enzyme induction is restricted largely to rodents (rats and mice) in vitro and in vivo. Feeding studies have shown that excretion of higher brominated BDEs is much greater than lower brominated BDEs. Penta-BDE is more toxic than octa- and deca-BDE following oral administration (oral LD50 in rats, 0.5-5 g/kg). In rodents, repeated exposure to PBDEs results in thyroid hormone disruption, developmental neurotoxicity, some changes of fetal development, and hepatotoxic effects. The observed chronic NOELs depend upon the technical mixture type (i.e., deca-, octa-, or penta- and their congener composition), animal species, and study protocol. Values range from 0.6 to 100 mg/kg in rats and from I to 100 mg/kg in mice. PBDEs are neither mutagenic nor genotoxic. Immunotoxicity in mice is observed following exposure to BDE-47 at 18 mg/kg/d, where splenocyte number decreased. Mice exposed neonatally to a single oral dose of BDE-47(10.5 mg/kg) or BDE-99 (12 mg/kg) on Pnd10 (period of rapid brain growth and development) show permanent impairment of spontaneous motor behavior when reaching adulthood. BDE-99 also induced adverse effects on learning and memory functions of mice. The estimated daily intake based on food consumption for PBDEs ranges from 44 to 51 ng/d, with fish contributing almost one-half. The BDE-99 body burden from a human milk survey can be estimated at 0.64 microg/kg, well below the experimental body burden of 0.4 mg/kg BDE-99 associated

Soil concentrations and source apportionment of polybrominated diphenyl ethers (PBDEs) and trace elements around a heavily industrialized area in Kocaeli, Turkey.

Science.gov (United States)

Cetin, Banu

2014-01-01

Air pollutants are transported by dry deposition, wet deposition, and gas exchange accumulated in soil. Therefore, soil is an important environmental medium reflecting the level and the spatial distribution of air pollutants such as polybrominated diphenyl ethers (PBDEs) and heavy metals. Soil concentrations of seven PBDE congeners and 21 trace elements were determined in a heavily industrialized region (Dilovasi) in Kocaeli, Turkey. At all sites, Σ7PBDE concentrations ranged from 0.70 to 203 with a mean value of 26.3 μg kg(-1) (dry weight). The congener profiles and mass inventories of PBDEs and their interactions with soil organic matter (SOM) were also investigated. BDE-209 was the dominant congener at all sites, followed by BDE-99 and/or -47. The estimated inventory of PBDEs for the Dilovasi district was 310 kg. However, there are several additional industrial regions in Kocaeli city. Considering the total land area, the potential inventory would be much larger for this city. The relationship between the PBDE concentrations in soil and SOM content indicated that factors other than soil properties have a greater influence on soil concentrations. Crustal enrichment factors (EFs) were determined; correlation analysis and factor analysis (FA) were also applied to generated data set to identify and apportion the sources polluting the soil. Sn, Mn, Ca, As, Zn, Pb, and Cd had significantly high average EF values, indicating that their soil concentrations were mainly influenced by anthropogenic activities. In FA, six factors were extracted with a cumulative variance of 84.4 % and industrial activities and traffic were found to be the main factors affecting the soil profile.

99Mo-99mTc production development by (n, γ) reaction

International Nuclear Information System (INIS)

Izumo, Hironobu; Nishikata, Kaori; Kimura, Akihiro; Tanimoto, Masataka; Tsuchiya, Kunihiko; Ishihara, Masahiro; Kaminaga, Masanori

2012-01-01

The renewed JMTR will be started from the later half of JFY2012, and it is expected to various fields. Supply of 99 Mo in Japan depends only on imports from foreign countries. JAEA has a plan to produce 99 Mo, a parent nuclide of 99m Tc. JMTR will contribute to produce 99 Mo by (n, r) method as one of effective uses of the JMTR. In this paper, outline of the technical study items for production method of 99 Mo- 99m Tc in JMTR will be described. (author)

A modified {sup 99} Mo- {sup 99} Tc generator on Zirconium molybdo- phosphate-{sup 99} Mo gel. Vol. 3

Energy Technology Data Exchange (ETDEWEB)

El-Kolaly, M T; Talaat, H [Labelled Compounds Department, Cairo (Egypt); Botros, N [Radioistspe and Generator Department, Radioisotope Production and Sealed Source Division, Hot Laboratories Center, Atomic Energy Authority, Cairo (Egypt)

1996-03-01

A modified {sup 99} Mo - {sup 99} Tc gel generator is described. The new generator is based on the use of zirconium molybdophosphate - {sup 99} Mo gel in which {sup 99} Mo chemically combined in the gel structure, where {sup 99m}Tc can be easily eluted with distilled water or saline. The gel was prepared via chemical reaction between zirconyl chloride and molybdophosphate - {sup 99} Mo solution. The PH of the reaction mixture was adjusted with NaOH. Different gels have been prepared by varying the molar ratio of Mo:Zr:p. The PH and time of digeston on complete gel formation was also investigated in order to optimize the condition of gel preparation. Molybdophosphate {sup 32} P solution was used to determine the phosphorous content in the gel and in the {sup 99m}Tc eluate. The temperature and time of drying of the gel and their effect on {sup 99m}Tc elution efficiency were also studied. From the data obtained, the optimum conditions for routine production of {sup 99} Mo - {sup 99m}Tc generator are presented and discussed. 2 figs., 6 tabs.

Occurrence of PCDD/F, PCB, PBDE, PFAS, and organotin compounds in fish meal, fish oil and fish feed.

Science.gov (United States)

Suominen, K; Hallikainen, A; Ruokojärvi, P; Airaksinen, R; Koponen, J; Rannikko, R; Kiviranta, H

2011-10-01

We analysed polychlorinated dibenzo-p-dioxins and furans (PCDD/F, dioxins), and polychlorinated biphenyls (PCB) in 13 fish meal, five fish oil, and seven fish feed samples. Polybrominated diphenyl ethers (PBDE), organotin compounds (OTC), and perfluoroalkylated substances (PFAS) were analysed in ten fish meal, two fish oil, and two fish feed samples. All measured TEQ concentrations of PCDD/F and PCB were below the maximum levels set by Directive 2002/32/EC. There was no correlation between concentrations of WHOPCDD/F-TEQ and indicator PCB in our samples. The most common congeners among PBDEs were BDE-47 and BDE-100. BDE-209 was present in five fish meals of the ten analysed. Tributyltin (TBT) was the predominant congener in all samples except in three fish meals, where monobutyltin (MBT) was the major congener. Perfluorooctane sulphonate (PFOS) was the predominant congener in six fish meals of the ten analysed. There was large variation in concentrations and congener distributions of the studied compounds between our samples. Our results underline a need to pay special attention to the origin and purity of feed raw material of marine origin. Copyright © 2011 Elsevier Ltd. All rights reserved.

Actin grips: circular actin-rich cytoskeletal structures that mediate the wrapping of polymeric microfibers by endothelial cells.

Science.gov (United States)

Jones, Desiree; Park, DoYoung; Anghelina, Mirela; Pécot, Thierry; Machiraju, Raghu; Xue, Ruipeng; Lannutti, John J; Thomas, Jessica; Cole, Sara L; Moldovan, Leni; Moldovan, Nicanor I

2015-06-01

Interaction of endothelial-lineage cells with three-dimensional substrates was much less studied than that with flat culture surfaces. We investigated the in vitro attachment of both mature endothelial cells (ECs) and of less differentiated EC colony-forming cells to poly-ε-capro-lactone (PCL) fibers with diameters in 5-20 μm range ('scaffold microfibers', SMFs). We found that notwithstanding the poor intrinsic adhesiveness to PCL, both cell types completely wrapped the SMFs after long-term cultivation, thus attaining a cylindrical morphology. In this system, both EC types grew vigorously for more than a week and became increasingly more differentiated, as shown by multiplexed gene expression. Three-dimensional reconstructions from multiphoton confocal microscopy images using custom software showed that the filamentous (F) actin bundles took a conspicuous ring-like organization around the SMFs. Unlike the classical F-actin-containing stress fibers, these rings were not associated with either focal adhesions or intermediate filaments. We also demonstrated that plasma membrane boundaries adjacent to these circular cytoskeletal structures were tightly yet dynamically apposed to the SMFs, for which reason we suggest to call them 'actin grips'. In conclusion, we describe a particular form of F-actin assembly with relevance for cytoskeletal organization in response to biomaterials, for endothelial-specific cell behavior in vitro and in vivo, and for tissue engineering. Copyright © 2015 Elsevier Ltd. All rights reserved.

Concentration of sup(99m)Tc from the eluate of 99Mo-sup(99m)Tc generators

International Nuclear Information System (INIS)

Saucedo, T.; Mora, M.; Fraga de Suarez, A.H.; Mitta, A.E.A.

1976-04-01

A method is described to concentrate sup(99m)Tc solutions, originated in 99 Mo-sup(99m)Tc generators, independent of its age. The techniques of preparation of the different radiopharmaceuticals used in nuclear medicine are also described. (author) [es

Problems in clinical practice of domestic supply of 99Mo/99mTc. Considerations on the domestic production of 99Mo/99mTc

International Nuclear Information System (INIS)

Yamabayashi, Hisamichi

2012-01-01

At present, a bulky import product, 99 Mo supplied in Japan is produced by a nuclear fission method which enables to produce a generator system with no need of commercially preparing 99m Tc-labeled radiopharmaceuticals due to its high specific activity. However its usage of enriched uranium target leads to avoiding the fission method from the option of domestic production. In order to secure the domestic supply of 99 Mo/ 99m Tc, the neutron activation method, aiming to meet about 20% of domestic demand, is under development along with the re-start program of JMTR. Development of various production methods using accelerators are also in progress. In those non-fission methods with reactors or accelerators, rapid and effective procedures for concentration and refinement of 99m Tc solution eluted from 99 Mo of low specific activity are the subjects to be considered for attaining the stable labeling performances. (author)

Accurate technetium-99 determination using the combination of TEVA resin pretreatment and ICP-MS measurement and its influence on the Tc-99/Cs-137 scaling factor calculation

International Nuclear Information System (INIS)

Lian-Song Chen; Tsing-Hai Wang; Yi-Kong Hsieh; Li-Wei Jian; Wie-Han Chen; Chu-Fang Wang; Tsuey-Lin Tsai

2014-01-01

Accurate determination of technetium-99 (Tc-99) is very important because any overestimation will cause the examined radioactive wastes to be categorized into super C class, which dramatically increases the cost of waste management. Herein, we demonstrated that by adopting the analytical method comprising TEVA resin pretreatment and ICP-MS measurement, the determined Tc-99 concentrations in representative waste stream samples from the Lan-Yu low-level radioactive waste temporary storage site in Taiwan were approximately two orders of magnitude lower than those determined from the beta radiation measurement using a low background liquid scintillation counter. Two important concerns emerged from our results. First, severe interferences from other nuclides residing in the matrix considerably affect the determination of Tc-99, even when a low background liquid scintillation counter was used. Second, the currently used Tc-99/Cs-137 scaling factor should be carefully revised, or it might lead to a considerable overestimation of the Tc-99 concentration. (author)

Development of 99mTc-DMSA for kidney imaging

International Nuclear Information System (INIS)

Shafii Khamis; Nurshuhadah Mohd Yusof

2006-01-01

In nuclear medicine studies, 99m Tc-Dimercaptosuccinic acid ( 99m Tc-DMSA) has been shown to be an excellent radiopharmaceutical agent for detecting focal abnormalities of the renal cortex in patients. The agent, however, oxidizes readily and must be used within 30 minutes of preparation. The instability of the radiopharmaceutical renders the kit less economical to use. Several factors affecting the labeling yield such as the kit formulation, stannous and stabilizer content were investigated. The radiochemical determination of the radiolabelled product was analyzed using I TLC-SG system developed in methyl ethyl ketone and the radiolabelled 99m Tc-DMSA biological distributions were carried out in female rats. Stability study of the radiolabelled 99m Tc-DMSA was carried out using ascorbic acid as stabilizer. Comparative study was also carried out on both the prepared kit and those obtained commercially. The DMSA kit was successfully developed and the result obtained was found to be comparable to that of the commercially available kit. (Author)

Why is cytoskeletal contraction required for cardiac fusion before but not after looping begins?

Science.gov (United States)

Shi, Yunfei; Varner, Victor D.; Taber, Larry A.

2015-02-01

Cytoskeletal contraction is crucial to numerous morphogenetic processes, but its role in early heart development is poorly understood. Studies in chick embryos have shown that inhibiting myosin-II-based contraction prior to Hamburger-Hamilton (HH) stage 10 (33 h incubation) impedes fusion of the mesodermal heart fields that create the primitive heart tube (HT), as well as the ensuing process of cardiac looping. If contraction is inhibited at or after looping begins at HH10, however, fusion and looping proceed relatively normally. To explore the mechanisms behind this seemingly fundamental change in behavior, we measured spatiotemporal distributions of tissue stiffness, stress, and strain around the anterior intestinal portal (AIP), the opening to the foregut where contraction and cardiac fusion occur. The results indicate that stiffness and tangential tension decreased bilaterally along the AIP with distance from the embryonic midline. The gradients in stiffness and tension, as well as strain rate, increased to peaks at HH9 (30 h) and decreased afterward. Exposure to the myosin II inhibitor blebbistatin reduced these effects, suggesting that they are mainly generated by active cytoskeletal contraction, and finite-element modeling indicates that the measured mechanical gradients are consistent with a relatively uniform contraction of the endodermal layer in conjunction with constraints imposed by the attached mesoderm. Taken together, our results suggest that, before HH10, endodermal contraction pulls the bilateral heart fields toward the midline where they fuse to create the HT. By HH10, however, the fusion process is far enough along to enable apposing cardiac progenitor cells to keep ‘zipping’ together during looping without the need for continued high contractile forces. These findings should shed new light on a perplexing question in early heart development.

Why is cytoskeletal contraction required for cardiac fusion before but not after looping begins?

International Nuclear Information System (INIS)

Shi, Yunfei; Taber, Larry A; Varner, Victor D

2015-01-01

Cytoskeletal contraction is crucial to numerous morphogenetic processes, but its role in early heart development is poorly understood. Studies in chick embryos have shown that inhibiting myosin-II-based contraction prior to Hamburger–Hamilton (HH) stage 10 (33 h incubation) impedes fusion of the mesodermal heart fields that create the primitive heart tube (HT), as well as the ensuing process of cardiac looping. If contraction is inhibited at or after looping begins at HH10, however, fusion and looping proceed relatively normally. To explore the mechanisms behind this seemingly fundamental change in behavior, we measured spatiotemporal distributions of tissue stiffness, stress, and strain around the anterior intestinal portal (AIP), the opening to the foregut where contraction and cardiac fusion occur. The results indicate that stiffness and tangential tension decreased bilaterally along the AIP with distance from the embryonic midline. The gradients in stiffness and tension, as well as strain rate, increased to peaks at HH9 (30 h) and decreased afterward. Exposure to the myosin II inhibitor blebbistatin reduced these effects, suggesting that they are mainly generated by active cytoskeletal contraction, and finite-element modeling indicates that the measured mechanical gradients are consistent with a relatively uniform contraction of the endodermal layer in conjunction with constraints imposed by the attached mesoderm. Taken together, our results suggest that, before HH10, endodermal contraction pulls the bilateral heart fields toward the midline where they fuse to create the HT. By HH10, however, the fusion process is far enough along to enable apposing cardiac progenitor cells to keep ‘zipping’ together during looping without the need for continued high contractile forces. These findings should shed new light on a perplexing question in early heart development. (paper)

Labelled Preformed liposomes with 99MTC-DTPA, 99 MTC-ECD, 99MTC-MDP and 99MTC-MIBI : Labelling procedures and stability studies

International Nuclear Information System (INIS)

Savio, E.O.; Teran, M.A.; Vales, M.E.; Frier, M.

2004-01-01

Liposomes labelled with gamma e miters like 99mTc, can be used for scintigraphic imaging to non-invasively track and quantify the distribution of liposomes in the body. In vitro studies were done to choose a suitable radiopharmaceutical (RF) to be attached to performed liposomes. 99mTc-Complexes (DTPA, ECD, MDP, MIBI) were used to label collagen liposomes. Commercial kits were labelled with 99mTc04-(TechnoNuclear). Quality controls of the RF were performed. Collagen liposomes suspended in saline 0.9% were incubated at 4.25.37 and 60 for 30 min. Efficiency of the labelling procedure was determined by gel filtration using Sephadex G25 (Pharmacia) and NaC10.9%. Samples of 100mL (74MBq), were seeded and fractions of 0.5mL were colleted and measured in an ionisation chamber (Capintec CRC). Stability of the labelled liposomes was assessed incubating 0.5mL, of the suspension with 1mL of human serum during 30 min at 37 . Dialysis was performed using dialysis bags of 64 K pore size and NaCI 0.9% at room temperature. Samples of the saline bath were collected at 30.60 and 90 min. and measured in a solid scintillation counter Ortec.Liposomes labelled with 99mTc-DTPA and 99mTcMIBI showed a labelling efficiency of 80%; liposomes incubated with 99mTc-MDP were labelled in a 50% and 99mTc-ECD did not bind to liposomes in the conditions of study. Incubation of labelled liposomes with human serum showed 50% of strong binding to the plasmatic proteins for 99mTc-DTPA but low values (5%) for the other specimens. Labelled liposomes were achieved, with different RF, showing a suitable in vitro stability to perform in vivo studies

Body burdens of brominated flame retardants and other persistent organo-halogenated compounds and their descriptors in US girls

Energy Technology Data Exchange (ETDEWEB)

Windham, Gayle C., E-mail: gayle.windham@cdph.ca.gov [CA Department of Public Health, DEODC, 850 Marina Bay Pkwy, Bldg. P, Richmond, CA 94804 (United States); Pinney, Susan M. [University of Cincinnati College of Medicine, Cincinnati, OH 45267 (United States); Sjodin, Andreas [Centers for Disease Control and Prevention, Atlanta, GA 30341 (United States); Lum, Raymond [Impact Assessment Inc., San Diego, CA (United States); Jones, Richard S.; Needham, Larry L. [Centers for Disease Control and Prevention, Atlanta, GA 30341 (United States); Biro, Frank M. [University of Cincinnati College of Medicine, Cincinnati, OH 45267 (United States); Hiatt, Robert A. [University of California Medical School, San Francisco, CA (United States); Kushi, Lawrence H. [Kaiser Permanente Northern California, Oakland, CA 94612 (United States)

2010-04-15

Background: Levels of brominated flame retardants are increasing in US populations, yet little data are available on body burdens of these and other persistent hormonally active agents (HAAs) in school-aged children. Exposures to such chemicals may affect a number of health outcomes related to development and reproductive function. Objective: Determine the distribution of biomarkers of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and organo-chlorinated pesticides (OCPs), such as DDT/DDE, in children, and their variation by key descriptor variables. Methods: Ethnically diverse cohorts of girls 6-8 y old at baseline are being followed for growth and pubertal development in a multi-site, longitudinal study. Nearly 600 serum samples from the California and Ohio sites were analyzed for lipids, 35 PCB congeners, 11 PBDE congeners, and 9 OCPs. The biomarker distributions were examined and geometric means compared for selected analytes across categories of age, race, site, body mass index (BMI), parental education, maternal age at delivery, and breast feeding in adjusted models. Results: Six PBDE congeners were detected among greater than 70% of samples, with BDE-47 having the highest concentration (median 42.2, range 4.9-855 ng/g lipid). Girls in California had adjusted geometric mean (GM) PBDE levels significantly higher than girls in Ohio. Furthermore, Blacks had significantly higher adjusted GMs of all six PBDE congeners than Whites, and Hispanics had intermediate values. GMs tended to be lower among more obese girls, while other variables were not strongly associated. In contrast, GMs of the six PCB congeners most frequently detected were significantly lower among Blacks and Hispanics than Whites. PCBs and the three pesticides most frequently detected were also consistently lower among girls with high BMI, who were not breast-fed, whose mothers were younger, or whose care-givers (usually parents) were less educated. Girls in California had

Body burdens of brominated flame retardants and other persistent organo-halogenated compounds and their descriptors in US girls

International Nuclear Information System (INIS)

Windham, Gayle C.; Pinney, Susan M.; Sjodin, Andreas; Lum, Raymond; Jones, Richard S.; Needham, Larry L.; Biro, Frank M.; Hiatt, Robert A.; Kushi, Lawrence H.

2010-01-01

Background: Levels of brominated flame retardants are increasing in US populations, yet little data are available on body burdens of these and other persistent hormonally active agents (HAAs) in school-aged children. Exposures to such chemicals may affect a number of health outcomes related to development and reproductive function. Objective: Determine the distribution of biomarkers of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and organo-chlorinated pesticides (OCPs), such as DDT/DDE, in children, and their variation by key descriptor variables. Methods: Ethnically diverse cohorts of girls 6-8 y old at baseline are being followed for growth and pubertal development in a multi-site, longitudinal study. Nearly 600 serum samples from the California and Ohio sites were analyzed for lipids, 35 PCB congeners, 11 PBDE congeners, and 9 OCPs. The biomarker distributions were examined and geometric means compared for selected analytes across categories of age, race, site, body mass index (BMI), parental education, maternal age at delivery, and breast feeding in adjusted models. Results: Six PBDE congeners were detected among greater than 70% of samples, with BDE-47 having the highest concentration (median 42.2, range 4.9-855 ng/g lipid). Girls in California had adjusted geometric mean (GM) PBDE levels significantly higher than girls in Ohio. Furthermore, Blacks had significantly higher adjusted GMs of all six PBDE congeners than Whites, and Hispanics had intermediate values. GMs tended to be lower among more obese girls, while other variables were not strongly associated. In contrast, GMs of the six PCB congeners most frequently detected were significantly lower among Blacks and Hispanics than Whites. PCBs and the three pesticides most frequently detected were also consistently lower among girls with high BMI, who were not breast-fed, whose mothers were younger, or whose care-givers (usually parents) were less educated. Girls in California had

Comparative study of 99Mo/99mTc generators at base of synthesized gels starting from activation and fission 99Mo

International Nuclear Information System (INIS)

Lopez M, I.Z.; Monroy G, F.; Rivero G, T.; Rojas N, P.

2007-01-01

The 99m Tc is used for diagnostic and therapy. It is produced starting from 99 Mo, absorbed in chromatographic columns, loaded with alumina that absorb only 0.2% of 99 Mo with high specific activities of 99 Mo, obtained from the 235 U fission. Given these conditions and limitations, new preparation procedures of 99 Mo/ 99m Tc generators, its have been developed, using zirconium molybdates gels that incorporates until 30% of 99 Mo, conserve similar characteristics of quality and purity that the traditional generator. The radiochemical characteristics of the 99m Tc elution, depend strongly on the gel preparation conditions. In particular, the present work has by object to determine the influence of the 99 Mo used type, fission or activation product, during the gels synthesis, as well as the used air flow for the agitation in the gels preparation and its influence in the 99 Mo/ 99m Tc generators quality. When diminishing the flow of agitation air the efficiency it increases and in the radionuclide purity of the eluates and when using 99 Mo from fission for the gels production it increases in an important way the elutriation efficiency, the radiochemical and radionuclide purity of the 99m Tc eluates. (Author)

Exposure to a PBDE/OH-BDE mixture alters juvenile zebrafish (Danio rerio) development.

Science.gov (United States)

Macaulay, Laura J; Chernick, Melissa; Chen, Albert; Hinton, David E; Bailey, Jordan M; Kullman, Seth W; Levin, Edward D; Stapleton, Heather M

2017-01-01

Polybrominated diphenyl ethers (PBDEs) and their metabolites (e.g., hydroxylated BDEs [OH-BDEs]) are contaminants frequently detected together in human tissues and are structurally similar to thyroid hormones. Thyroid hormones partially mediate metamorphic transitions between life stages in zebrafish, making this a critical developmental window that may be vulnerable to chemicals disrupting thyroid signaling. In the present study, zebrafish were exposed to 6-OH-BDE-47 (30 nM; 15 μg/L) alone, or to a low-dose (30 μg/L) or high-dose (600 μg/L) mixture of PentaBDEs, 6-OH-BDE-47 (0.5-6 μg/L), and 2,4,6-tribromophenol (5-100 μg/L) during juvenile development (9-23 d postfertilization) and evaluated for developmental endpoints mediated by thyroid hormone signaling. Fish were sampled at 3 time points and examined for developmental and skeletal morphology, apical thyroid and skeletal gene markers, and modifications in swimming behavior (as adults). Exposure to the high-dose mixture resulted in >85% mortality within 1 wk of exposure, despite being below reported acute toxicity thresholds for individual congeners. The low-dose mixture and 6-OH-BDE-47 groups exhibited reductions in body length and delayed maturation, specifically relating to swim bladder, fin, and pigmentation development. Reduced skeletal ossification was also observed in 6-OH-BDE-47-treated fish. Assessment of thyroid and osteochondral gene regulatory networks demonstrated significantly increased expression of genes that regulate skeletal development and thyroid hormones. Overall, these results indicate that exposures to PBDE/OH-BDE mixtures adversely impact zebrafish maturation during metamorphosis. Environ Toxicol Chem 2017;36:36-48. © 2016 SETAC. © 2016 SETAC.

In vivo and in vitro anti-androgenic effects of DE-71, a commercial polybrominated diphenyl ether (PBDE) mixture

International Nuclear Information System (INIS)

Stoker, T.E.; Cooper, R.L.; Lambright, C.S.; Wilson, V.S.; Furr, J.; Gray, L.E.

2005-01-01

PBDEs have been synthesized in large quantities as flame retardants for commercial products, such as electronic equipment and textiles. The rising in levels of PBDEs in tissues in wildlife species and in human milk and plasma samples over the past several years have raised concerns about possible health effects. Recently, we showed that the PBDE mixture, DE-71, delayed puberty and suppressed the growth of androgen-dependent tissues in male Wistar rat following a peri-pubertal exposure. These effects suggested that DE-71 may be either inducing steroid hormone metabolism or acting as an androgen receptor (AR) antagonist. To elucidate the potential anti-androgenic effects of this mixture, we evaluated DE-71 in several in vivo assays, which are responsive to alterations in androgen activity. In a pubertal exposure study designed to further evaluate the delay in preputial separation (PPS), we observed a dose-dependent delay in PPS with 60 and 120 mg/kg/day of DE-71 (4 and 5 days) and a corresponding suppression of ventral prostate (VP) and seminal vesicle growth at both doses. Adult males exposed to 60 mg/kg DE-71 for 3 days resulted in a significant increase in luteinizing hormone and a non-significant increase in testosterone, androstenedione and estrone. DE-71 also tested positive for anti-androgenic activity in an immature rat Hershberger assay, with decreases in mean VP and seminal vesicle weight following doses of 30-240 mg/kg. DE-71 and the individual BDE congeners which comprise the mixture (BDE-47, -99, -100, -153, -154) were also evaluated in vitro. First, AR binding was evaluated in a competitive binding assay using rat VP cytosol. In addition, we evaluated gene activation in a transcriptional activation assay using the MDA-kb2 cell line which contains an endogenous human AR and a transfected luciferase reporter. DE-71 and BDE-100 (2, 4, 6-pentaBDE) both inhibited AR binding, with IC50s of approximately 5 μM. In addition, DE-71 and two of the congeners (BDE

Gentc99m, computational system for the technetium-99m generator

International Nuclear Information System (INIS)

Suparman, I.

1997-01-01

The technetium-99m generator is one of the main products of the PPR, as the continuity of the technetium-99m generator production is important for supporting the development of nuclear medicine. GENTC99M has been made for computational for the technetium-99m generator and includes data processing, documentation and information GENTC99M is also very useful in quality control application especially for the determinations of yield and radionuclidic impurities which consume much time. microsoft visual basic for MS-DOS and visual basic for windows have been used for making GENTC99M. Microsoft visual basic has several features that make it an ideal development language for both MS-DOS and Microsoft Windows. These features not only increase productivity, they also provide all the tools and hooks needed to develop some very sophisticated applications. for a production centre like PPR, GENTC99M is very useful to support the data processing, documentation and information system of the technetium-99m generator and it can also be modified for other products

Spatiotemporal patterns and relationships among the diet, biochemistry, and exposure to flame retardants in an apex avian predator, the peregrine falcon.

Science.gov (United States)

Fernie, Kim J; Chabot, Dominique; Champoux, Louise; Brimble, Samantha; Alaee, Mehran; Marteinson, Sarah; Chen, Da; Palace, Vince; Bird, David M; Letcher, Robert J

2017-10-01

Flame retardants (FR) are industrial chemicals and some are proven environmental contaminants that accumulate in predatory birds. Few studies have examined the influence of diet on FR profiles in nestling raptors and the possible physiological implications of such FR exposure. The objectives of this research were (1) to determine spatial patterns of ≤ 48 polybrominated diphenyl ether (PBDE) congeners and ≤ 26 non-PBDE FRs, including organophosphate esters (OPEs), in nestling peregrine falcons (Falco peregrinus) across the Canadian Great Lakes-St. Lawrence River Basin (GL-SLR; 2010) and in the eastern Canadian Arctic (2007); (2) to identify temporal changes in FR concentrations from the mid-2000s to 2010 in GL-SLR peregrine nestlings; (3) to investigate the role of diet using stable isotopes on exposure patterns of quantifiable FRs; and (4) to assess possible associations between circulating FRs and total (T) thyroxine (TT 4 ) and triiodothyronine (TT 3 ), tocopherol, retinol and oxidative status (isoprostanes). The summed concentrations of the top 5 PBDEs (Σ 5 ) (BDE-47, -99, -100, -154, -153) were significantly higher in rural nestlings than urban nestlings in the GL-SLR, followed by the eastern Arctic nestlings. The PBDE congener profile of rural nestlings was dominated by BDE-99 (34‰), whereas BDE-209 (31‰) became dominant in the 2010 urban PBDE profile marking a shift since the mid-2000s. Low (ppb) concentrations of 25 novel non-PBDE FRs (e.g., 1,2-bis-(2,4,6-tribromophenoxy)ethane (BTBPE), decabromodiphenylethane (DBDPE)) were measured in the nestlings in at least one region, with the first report in peregrines of 15 novel non-PBDE FRs (e.g., 2-ethyl-1-hyxyl 2,3,4,5-tetrabromobenzoate (EHTBB), pentabromo allyl ether (PBPAE), tetrabromoethylcyclohexane (α-, β-DBE-DBCH)) as well as of tris (2-butoxyethyl) phosphate (TBOEP) (0-7.5ng/g ww) > tris(2-chloroisopropyl) phosphate (TCIPP) (0.1-5.5ng/g ww) > tris(2-chloroethyl) phosphate (TCEP) (0.02-2.0ng

Polybrominated diphenyl ethers in atmosphere and soil of a production area in China: levels and partitioning.

Science.gov (United States)

Jin, Jun; Wang, Ying; Liu, Weizhi; Yang, Congqiao; Hu, Jicheng; Cui, Jian

2011-01-01

Polybrominated diphenyl ethers (PBDEs) were measured in atmosphere and soil samples taken in winter and summer at a PBDE production area of Laizhou Bay in China. The concentrations of Sigma11PBDE were 0.017-1.17 ng/m3 in gaseous phase, 0.5-161.1 ng/m3 in particulate phase, and 73-2629 ng/g dry weight in soil samples. The PBDE congener pattern in the gaseous phase differed from that in the particulate phase, and the PBDE congener pattern in the particulate phase was similar with that in soil. This demonstrated that there was little difference with atmospheric particle-soil transfer efficiency among PBDE congeners. In addition, there were seasonal variations in percentages on particle for lower brominated congeners. The BDE-28 was mostly in the gaseous phase in summer (88.3%), whereas the average proportion of BDE-28 in gaseous phase in winter was 38.9%. Higher brominated congeners (i.e., BDE-206, BDE-207, BDE-208, and BDE-209) were bound to the atmospheric particulate phase, and their potentials for long-range migration were mainly affected by the environmental behavior of atmospheric particles. Results indicated that PBDE congeners in summer were closer to gas-particle partition equilibrium than in winter. Temperature should be considered the main factor causing nonequilibrium in winter.

Polybrominated diphenyl ethers in atmosphere and soil of a production area in China: Levels and partitioning

Institute of Scientific and Technical Information of China (English)

Jun Jin; Ying Wang; Weizhi Liu; Congqiao Yang; Jicheng Hu; Jian Cui

2011-01-01

Polybrominated diphenyl ethers (PBDEs) were measured in atmosphere and soil samples taken in winter and summer at a PBDE production area of Laizhou Bay in China. The concentrations of ∑11 PBDE were 0.017-1.17 ng/m3 in gaseous phase, 0.5-161.1 ng/m3 in particulate phase, and 73-2629 ng/g dry weight in soil samples. The PBDE congener pattern in the gaseous phase differed from that in the particulate phase, and the PBDE congener pattern in the particulate phase was similar with that in soil. This demonstrated that there was little difference with atmospheric panicle-soil transfer efficiency among PBDE congeners. In addition, there were seasonal variations in percentages on particle for lower brominated congeners. The BDE-28 was mostly in the gaseous phase in summer (88.3％),whereas the average proportion of BDE-28 in gaseous phase in winter was 38.9％. Higher brominated congeners (i.e., BDE-206, BDE207, BDE-208, and BDE-209) were bound to the atmospheric particulate phase, and their potentials for long-range migration were mainly affected by the environmental behavior of atmospheric particles. Results indicated that PBDE congeners in summer were closer to gas-particle partition equilibrium than in winter. Temperature should be considered the main factor causing nonequilibrium in winter.

Availability of 99Tc in undisturbed soil cores

International Nuclear Information System (INIS)

Denys, Sebastien; Echevarria, Guillaume; Florentin, Louis; Leclerc-Cessac, Elisabeth; Morel, Jean-Louis

2003-01-01

Models for safety assessment of radioactive waste repositories need accurate values of the soil-to-plant transfer of radionuclides. In oxidizing environments, 99 Tc is expected to occur as pertechnetate ( 99 TcO 4 - ). Due to its high mobility, leaching of this element in the field might be important, potentially affecting the reliability of estimated transfer parameters of 99 Tc as measured in closed experimental systems such as hydroponics or pot experiments. The aim of this experiment was to measure the leaching of 99 Tc in undisturbed irrigated soil cores under cultivation as well as plant uptake and to study the possible competition between the two transfer pathways. Undisturbed soil cores (50x50 cm) were sampled from a Rendzic Leptosol (R), a colluvial Fluvic Cambisol (F) and a Dystric Cambisol (D) using PVC tubes (three cores sampled per soil type). Each core was equipped with a leachate collector at the bottom, allowing the monitoring of 99 Tc leaching through the cores. Cores were placed in a greenhouse and maize (Zea mays L., cv. DEA, Pioneer[reg]) was sown. After 135 d, maize was harvested and radioactivity determined in both plant and water samples. Results showed that during the growing period, leaching of 99 Tc was limited, due to the high evapotranspiration rate of maize. After harvest, leaching of 99 Tc went on because of the absence of evapotranspiration. Effective uptake (EU) of 99 Tc in leaves and grains was calculated. EU reached 70% of the input in the leaves and was not significantly different among soils. These results confirmed those obtained from pot experiments, even though leaching was allowed to occur in close-to-reality hydraulical conditions. As a consequence, it was concluded that pot experiments are an adequate surrogate for more complex 'close-to-reality' experimental systems for measuring transfer factors

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

Science.gov (United States)

Appert-Rolland, C.; Ebbinghaus, M.; Santen, L.

2015-09-01

Cells are the elementary units of living organisms, which are able to carry out many vital functions. These functions rely on active processes on a microscopic scale. Therefore, they are strongly out-of-equilibrium systems, which are driven by continuous energy supply. The tasks that have to be performed in order to maintain the cell alive require transportation of various ingredients, some being small, others being large. Intracellular transport processes are able to induce concentration gradients and to carry objects to specific targets. These processes cannot be carried out only by diffusion, as cells may be crowded, and quite elongated on molecular scales. Therefore active transport has to be organized. The cytoskeleton, which is composed of three types of filaments (microtubules, actin and intermediate filaments), determines the shape of the cell, and plays a role in cell motion. It also serves as a road network for a special kind of vehicles, namely the cytoskeletal motors. These molecules can attach to a cytoskeletal filament, perform directed motion, possibly carrying along some cargo, and then detach. It is a central issue to understand how intracellular transport driven by molecular motors is regulated. The interest for this type of question was enhanced when it was discovered that intracellular transport breakdown is one of the signatures of some neuronal diseases like the Alzheimer. We give a survey of the current knowledge on microtubule based intracellular transport. Our review includes on the one hand an overview of biological facts, obtained from experiments, and on the other hand a presentation of some modeling attempts based on cellular automata. We present some background knowledge on the original and variants of the TASEP (Totally Asymmetric Simple Exclusion Process), before turning to more application oriented models. After addressing microtubule based transport in general, with a focus on in vitro experiments, and on cooperative effects in the

Quinolinic acid induces disrupts cytoskeletal homeostasis in striatal neurons. Protective role of astrocyte-neuron interaction.

Science.gov (United States)

Pierozan, Paula; Ferreira, Fernanda; de Lima, Bárbara Ortiz; Pessoa-Pureur, Regina

2015-02-01

Quinolinic acid (QUIN) is an endogenous metabolite of the kynurenine pathway involved in several neurological disorders. Among the several mechanisms involved in QUIN-mediated toxicity, disruption of the cytoskeleton has been demonstrated in striatally injected rats and in striatal slices. The present work searched for the actions of QUIN in primary striatal neurons. Neurons exposed to 10 µM QUIN presented hyperphosphorylated neurofilament (NF) subunits (NFL, NFM, and NFH). Hyperphosphorylation was abrogated in the presence of protein kinase A and protein kinase C inhibitors H89 (20 μM) and staurosporine (10 nM), respectively, as well as by specific antagonists to N-methyl-D-aspartate (50 µM DL-AP5) and metabotropic glutamate receptor 1 (100 µM MPEP). Also, intra- and extracellular Ca(2+) chelators (10 µM BAPTA-AM and 1 mM EGTA, respectively) and Ca(2+) influx through L-type voltage-dependent Ca(2+) channel (10 µM verapamil) are implicated in QUIN-mediated effects. Cells immunostained for the neuronal markers βIII-tubulin and microtubule-associated protein 2 showed altered neurite/neuron ratios and neurite outgrowth. NF hyperphosphorylation and morphological alterations were totally prevented by conditioned medium from QUIN-treated astrocytes. Cocultured astrocytes and neurons interacted with one another reciprocally, protecting them against QUIN injury. Cocultured cells preserved their cytoskeletal organization and cell morphology together with unaltered activity of the phosphorylating system associated with the cytoskeleton. This article describes cytoskeletal disruption as one of the most relevant actions of QUIN toxicity in striatal neurons in culture with soluble factors secreted by astrocytes, with neuron-astrocyte interaction playing a role in neuroprotection. © 2014 Wiley Periodicals, Inc.

The Drosophila HEM-2/NAP1 homolog KETTE controls axonal pathfinding and cytoskeletal organization.

Science.gov (United States)

Hummel, T; Leifker, K; Klämbt, C

2000-04-01

In Drosophila, the correct formation of the segmental commissures depends on neuron-glial interactions at the midline. The VUM midline neurons extend axons along which glial cells migrate in between anterior and posterior commissures. Here, we show that the gene kette is required for the normal projection of the VUM axons and subsequently disrupts glial migration. Axonal projection defects are also found for many other moto- and interneurons. In addition, kette affects the cell morphology of mesodermal and epidermal derivatives, which show an abnormal actin cytoskeleton. The KETTE protein is homologous to the transmembrane protein HEM-2/NAP1 evolutionary conserved from worms to vertebrates. In vitro analysis has shown a specific interaction of the vertebrate HEM-2/NAP1 with the SH2-SH3 adapter protein NCK and the small GTPase RAC1, which both have been implicated in regulating cytoskeleton organization and axonal growth. Hypomorphic kette mutations lead to axonal defects similar to mutations in the Drosophila NCK homolog dreadlocks. Furthermore, we show that kette and dock mutants genetically interact. NCK is thought to interact with the small G proteins RAC1 and CDC42, which play a role in axonal growth. In line with these observations, a kette phenocopy can be obtained following directed expression of mutant DCDC42 or DRAC1 in the CNS midline. In addition, the kette mutant phenotype can be partially rescued by expression of an activated DRAC1 transgene. Our data suggest an important role of the HEM-2 protein in cytoskeletal organization during axonal pathfinding.

The effect of the cytoskeletal inhibitors on the splenic lymphocyte traffic and homing in rats

International Nuclear Information System (INIS)

Yang Huibin

1989-01-01

The rat splenic lymphocyte traffic and homing in vivo and the effect of cytoskeletal inhibitors on this process were investigated using the technique of γ-counting of 51 Cr-labelled lymphocytes. The results suggests that:(1) After 2 of intravenous injection, the 51 Cr-labelled lymphocytes from donor rat spleen mainly home to recipient rat spleen, liver, lungs, mesenteric lymph modes (MLN) and gut-associated lymphoid tissues. (2) A significant inhibiting effect on the ability of preferential homing of splenic lymphocytes treated with sodium azide, cytochalasin B or colchicine shows that microtubles and microfilaments play an important role in the lymphocyte traffic and homing

Preparation of 99Mo/99mTc generators based on 99Mo zirconium molybdates in the Gel Synthesis Device for Generators

International Nuclear Information System (INIS)

Lopez M, I. Z.; Monroy G, F.; Rivero G, T.; Rojas N, P.

2008-01-01

The 99m Tc is used for diagnosis and therapy. It is produced commercially from 99 Mo obtained from the fission of 235 U, which is retained in chromatographic columns filled with alumina whose maximum capacity is 0.2%. Given these constraints new methods of preparation 99 Mo/ 99m Tc generators have been developed using zirconium molybdates gels containing up to 30% of Mo, which is part of the generator matrix, and retaining quality and purity similar characteristics to those commercial generators. The present study aims to determine the flow of agitation, temperature and drying time optimal to prepare 99 Mo/ 99m Tc generators based on 99 Mo zirconium molybdates in the Gel Synthesis Device 99 Mo/ 99m Tc Generators designed and built by groups of the Radioactive Materials Research Laboratory and Automation and Instrumentation Department of the National Institute of Nuclear Research. (Author)

The transmembrane collagen COL-99 guides longitudinally extending axons in C. elegans.

Science.gov (United States)

Taylor, Jesse; Unsoeld, Thomas; Hutter, Harald

2018-06-01

We have identified the transmembrane collagen, COL-99, in a genetic screen for novel genes involved in axon guidance in the nematode C. elegans. COL-99 is similar to transmembrane collagens type XIII, XXIII and XXV in vertebrates. col-99 mutants exhibit guidance defects in axons extending along the major longitudinal axon tracts, most prominently the left ventral nerve cord (VNC). COL-99 is expressed in the hypodermis during the time of axon outgrowth. We provide evidence that a furin cleavage site in COL-99 is essential for function, suggesting that COL-99 is released from the cells producing it. Vertebrate homologs of COL-99 have been shown to be expressed in mammalian nervous systems and linked to various neurological disease but have not been associated with guidance of extending neurons. col-99 acts genetically with the discoidin domain receptors ddr-1 and ddr-2, which are expressed by neurons affected in col-99 mutants. Discoidin domain receptors are activated by collagens in vertebrates. DDR-1 and DDR-2 may function as receptors for COL-99. Our results establish a novel role for a transmembrane collagen in axonal guidance and asymmetry establishment of the VNC. Copyright © 2018 Elsevier Inc. All rights reserved.

Altered [99mTc]Tc-MDP biodistribution from neutron activation sourced 99Mo.

Science.gov (United States)

Demeter, Sandor; Szweda, Roman; Patterson, Judy; Grigoryan, Marine

2018-01-01

Given potential worldwide shortages of fission sourced 99 Mo/ 99m Tc medical isotopes there is increasing interest in alternate production strategies. A neutron activated 99 Mo source was utilized in a single center phase III open label study comparing 99m Tc, as 99m Tc Methylene Diphosphonate ([ 99m Tc]Tc-MDP), obtained from solvent generator separation of neutron activation produced 99 Mo, versus nuclear reactor produced 99 Mo (e.g., fission sourced) in oncology patients for which an [ 99m Tc]Tc-MDP bone scan would normally have been indicated. Despite the investigational [ 99m Tc]Tc-MDP passing all standard, and above standard of care, quality assurance tests, which would normally be sufficient to allow human administration, there was altered biodistribution which could lead to erroneous clinical interpretation. The cause of the altered biodistribution remains unknown and requires further research.

Small-molecule intramimics of formin autoinhibition: a new strategy to target the cytoskeletal remodeling machinery in cancer cells.

Science.gov (United States)

Lash, L Leanne; Wallar, Bradley J; Turner, Julie D; Vroegop, Steven M; Kilkuskie, Robert E; Kitchen-Goosen, Susan M; Xu, H Eric; Alberts, Arthur S

2013-11-15

Although the cancer cell cytoskeleton is a clinically validated target, few new strategies have emerged for selectively targeting cell division by modulating the cytoskeletal structure, particularly ways that could avoid the cardiotoxic and neurotoxic effects of current agents such as taxanes. We address this gap by describing a novel class of small-molecule agonists of the mammalian Diaphanous (mDia)-related formins, which act downstream of Rho GTPases to assemble actin filaments, and their organization with microfilaments to establish and maintain cell polarity during migration and asymmetric division. GTP-bound Rho activates mDia family members by disrupting the interaction between the DID and DAD autoregulatory domains, which releases the FH2 domain to modulate actin and microtubule dynamics. In screening for DID-DAD disruptors that activate mDia, we identified two molecules called intramimics (IMM-01 and -02) that were sufficient to trigger actin assembly and microtubule stabilization, serum response factor-mediated gene expression, cell-cycle arrest, and apoptosis. In vivo analysis of IMM-01 and -02 established their ability to slow tumor growth in a mouse xenograft model of colon cancer. Taken together, our work establishes the use of intramimics and mDia-related formins as a new general strategy for therapeutic targeting of the cytoskeletal remodeling machinery of cancer cells. ©2013 AACR

Binding of 2,2',4,4',6-pentabromodiphenyl ether (BDE-100) and/or its metabolites to mammalian biliary carrier proteins

Energy Technology Data Exchange (ETDEWEB)

Larsen, G.; Huwe, J.; Hakk, H. [USDA ARS Biosciences Research Lab, Fargo, ND (United States); Low, M.; Rutherford, D. [Concordia College, Moorhead, MN (United States)

2004-09-15

Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in the textile and electronics industries and are globally produced in the range of 150,000 tons annually. Because they are very lipophilic, structurally similar to polychlorinated dibenzo-p-dioxins and biphenyls, environmentally persistent, and display an increasing number of toxicological effects, there is growing concern that this class of compounds may be emerging as a new environmental contaminant. Recent reports have documented their presence in human plasma, milk, and adipose tissue and in aquatic species such as sperm whales, harbor seals, and whitebeaked dolphins. Only a few PBDE congeners are consistently found and reported in the environment, e.g. BDE-47, 99, 100, 153 and 154, and 209. Of this group, only BDE-47 and 99 have been studied in mammals. Halogenated aromatic hydrocarbons can associate with endogenous carrier proteins in the urine and bile of rats, either as the parent or as metabolites. Toxic and non-toxic dioxins, PCB's, and PBDE's all have this capacity. Based on its lipophilicity, BDE-100 would be expected to require carrier proteins for mammalian in vivo transport. The purpose of the association has not been established but may be part of the process involved in mammalian elimination of these xenobiotics. However, the association may affect the normal function of these carrier proteins. One of the purposes of the present research was to administer a single oral dose of BDE-100 to male rats and measure the amount eliminated in the urine and bile, as well as characterize the nature and extent of binding to any proteins in these excreta.

Effect of technetium-99m on iodine-131 thyroid uptake measurements

International Nuclear Information System (INIS)

Wasserman, H.J.; Klopper, J.F.; Erlank, P.

1985-01-01

Following administration of 2.5-5.0 mCi[/sup 99m/Tc]pertechnetate, several hundred microcuries may be present in the necks of hyperthyroid patients after 6 hr. Coincidence summing of Tc-99m photons may disturb I-131 uptake measurements in such patients if an oral diagnostic dose of I-131 is administered immediately after completion of a [/sup 99m/Tc]pertechnetate scintigram. Using a lower discriminator level of 300 keV, false increases of 10%-50% may occur at 6 hr. The 24-hr uptake is also affected if an I-131 predose measurement is performed after administration of the Tc-99m dose. The authors have shown that these errors may be prevented by using a 1-mm lead filter in front of the scintillation detector. The attenuation of Tc-99m photons by the filter effectively eliminates summation pulses while it reduces the I-131 count rate by approximately 28%

Preparation and biological profile of 99mTc-lidocaine as a cardioselective imaging agent using 99mTc eluted from 99Mo/99mTc generator based on Al-Mo gel

International Nuclear Information System (INIS)

Sakr, T.M.; October University of Modern Sciences and Arts; Ibrahim, A.B.; Rashed, H.M.; Fasih, T.W.

2017-01-01

The current study is aimed to prepare 99m Tc-lidocaine as a new myocardial perfusion-imaging agent. The used 99m Tc was obtained from Al- 99 Mo-molybdate(VI) gel matrix. 99m Tc-lidocaine showed higher (15.4 ± 0.11% ID/g) and faster (15 min post injection) cardiac uptake than the recently studied 99m Tc-valsartan and 99m Tc-procainamide. Consequently, 99m Tc-lidocaine will be a valuable myocardial SPECT agent for diagnosis of emergency patients. Besides, the receptor affinity study confirmed the selectivity of 99m Tc-lidocaine for sodium channels in the heart. (author)

Expression of cytoskeletal and matrix genes following exposure to ionizing radiation: Dose-rate effects and protein synthesis requirements

International Nuclear Information System (INIS)

Woloschak, G.E.

1994-01-01

Experiments were designed to examine the effects Of radiation dose-rate and of the protein synthesis inhibitor cycloheximide on expression of cytoskeletal elements (γ- and β-actin and α-tubulin) and matrix elements (fibronectin) in Syrian hamster embryo cells. Past work from our laboratory had already demonstrated optimum time points and doses for examination of radiation effects on accumulation of specific transcripts. Our results here demonstrated little effect of dose-rate for JANUS fission spectrum neutrons when comparing expression of either α-tubulin or fibronectin genes. Past work had already documented similar results for expression of actin transcripts. Effects of cycloheximide revealed that cycloheximide repressed accumulation of α-tubulin following exposure to high dose-rate neutrons or γ rays; this did not occur following similar low dose-rate exposure. (2) Cycloheximide did not affect accumulation of MRNA for actin genes; and that cycloheximide abrogated the moderate induction of fibronectin-mRNA which occurred following exposure to γ rays and high dose-rate neutrons. These results suggest a role for labile proteins in the maintenance of α-tubulin and fibronectin MRNA accumulation following exposure to ionizing radiation. in addition, they suggest that the cellular/molecular response to low dose-rate neutrons may be different from the response to high dose-rate neutrons

Comparative study of 99Mo/99mTc generators at base of synthesized gels starting from 99Mo of activation and of fission

International Nuclear Information System (INIS)

Lopez M, I.Z.; Monroy G, F.; Rivero G, T.; Rojas N, P.

2007-01-01

At the present time the more used and diffused radionuclide in nuclear medicine it is the Technetium 99 metastable ( 99 mTc) it is used for diagnostic and therapy. It is produced starting from molybdenum 99 ( 99 Mo), which is absorbed in chromatographic columns, loaded with alumina that absorb only 0.2% of 99 Mo situation that forces to use high specific activities of 99 Mo that it is obtained starting from the fission of the 235 U. Given these conditions and limitations, new preparation procedures of 99 Mo/ 99m Tc generators, of low or medium specific activity, its have been developed, using gels of zirconium molybdates that incorporates until 30% in weight of 99 Mo in the gel, and also conserve similar characteristics of quality and purity that those obtained by the traditional generator; reducing by this way the cost of production of the 99m Tc, when using 99 Mo of low specific activity, in the preparation of 99 Mo/ 99m Tc generators. The radiochemical characteristics of the elution of 99m Tc, depends strongly on the gel preparation conditions. In particular, the present work has for object to determine the influence of the used type of 99 Mo, fission or activation product, during the gels synthesis, as well as the used air flow for the agitation in the gels preparation and its influence in the quality of the 99 Mo/ 99m Tc generators. When diminishing the agitation air flow the efficiency it increases and in the radionuclide purity of the eluates and when using 99 Mo of fission for the gels production it increases in an important way the elution efficiency, the radiochemical purity and radionuclide of the eluates of 99m Tc. (Author)

Technetium-99 in ''instant'' sup(99m)Tc-pertechnetate

International Nuclear Information System (INIS)

Mattsson, S.

1978-01-01

The 99 Tc-content in sup(99m)Tc-pertechnetate separated from 99 Mo by distillation or extraction has been studied with a plastic scintillation detector. The identification of the measured activity was achieved by beta-spectrometry, chemical separation and half-life studies. The frequency distribution of the sup(99)Tc/sup(99m)Tc-ratios in the different samples was observed to be log-normal. The most likely activity ratio was 0.4x10 -6 , the maximum value being 5x10 -6 . The specific activity of ''instant'' pertechnetate is approximately a factor of 60 lower than that normally recorded in pertechnetate derived from daily eluted column generators. The low specific activity of ''instant'' pertechnetate is primarily explained by the long time between separation and usage and secondly by the low yield of Tc in the distillation and extraction processes. In several of the ''instant'' pertechnetate solutions the carrier concentration exceeded the reductive capacity of the stannous ions in ''kits'' with small amounts of Sn(II) in usable form. (T.G.)

Potential Ways to Address Shortage Situations of 99Mo/99mTc.

Science.gov (United States)

Filzen, Leah M; Ellingson, Lacey R; Paulsen, Andrew M; Hung, Joseph C

2017-03-01

99m Tc, the most common radioisotope used in nuclear medicine, is produced in a nuclear reactor from the decay of 99 Mo. There are only a few aging nuclear reactors around the world that produce 99 Mo, and one of the major contributors, the National Research Universal (Canada), ceased production on October 31, 2016. The National Research Universal produced approximately 40% of the world's 99 Mo supply, so with its shut down, shortages of 99 Mo/ 99m Tc are expected. Methods: Nuclear pharmacies and nuclear medicine departments throughout the United States were contacted and asked to provide their strategies for coping with a shortage of 99 Mo/ 99m Tc. Each of these strategies was evaluated on the basis of its effectiveness for conserving 99m Tc while still meeting the needs of the patients. Results: From the responses, the following 6 categories of strategies, in order of importance, were compiled: contractual agreements with commercial nuclear pharmacies, alternative imaging protocols, changes in imaging schedules, software use, generator management, and reduction of ordered doses or elimination of backup doses. Conclusion: The supply chain of 99 Mo/ 99m Tc is quite fragile; therefore, being aware of the most appropriate coping strategies is crucial. It is essential to build a strong collaboration between the nuclear pharmacy and nuclear medicine department during a shortage situation. With both nuclear medicine departments and nuclear pharmacies implementing viable strategies, such as the ones proposed, the amount of 99m Tc available during a shortage situation can be maximized. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Polybrominated Diphenyl Ether Exposure and Thyroid Function Tests in North American Adults.

Science.gov (United States)

Makey, Colleen M; McClean, Michael D; Braverman, Lewis E; Pearce, Elizabeth N; He, Xue-Mei; Sjödin, Andreas; Weinberg, Janice M; Webster, Thomas F

2016-04-01

Polybrominated diphenyl ethers (PBDEs) are flame-retardant chemicals that are added to many consumer products. Multiple animal studies have shown PBDEs to be thyroid hormone (TH) disruptors. Epidemiologic evidence of PBDE exposure associated with TH disruption has been inconclusive. We used repeated measures to estimate associations between serum PBDE concentrations and THs in a North American adult cohort. From 2010 to 2011, we collected ≤ 3 serum samples at approximately 6-month intervals from 52 healthy adult office workers from Boston, Massachusetts, for analysis of PBDE congeners and THs. The geometric mean sum concentrations of the most prevalent PBDE congeners (BDE-28, BDE-47, BDE-99, BDE-100, and BDE-153) were 22 ng/g lipid in winter 2010, 23 ng/g lipid in summer 2010, and 19 ng/g lipid in winter 2011. BDE-47 was the predominant congener. Based on a multivariable mixed regression model, we estimated that on average, a 1-ng/g serum increase in BDE-47 was associated with a 2.6-μg/dL decrease in total thyroxine (T4) (95% CI: -4.7, -0.35). Total T4 was inversely associated with each PBDE congener. Serum concentrations of PBDEs were not strongly associated with total triiodothyronine (T3), free T4, or thyroid-stimulating hormone (TSH). These results are consistent with those from animal studies showing that exposure to PBDEs is associated with a decrease in serum T4. Because the other TH concentrations did not appear to be associated with BDE exposures, our findings do not indicate effects on the pituitary-thyroid axis. Taken together, our findings suggest that PBDE exposure might decrease the binding of T4 to serum T4 binding proteins. Makey CM, McClean MD, Braverman LE, Pearce EN, He XM, Sjödin A, Weinberg JM, Webster TF. 2016. Polybrominated diphenyl ether exposure and thyroid function tests in North American adults. Environ Health Perspect 124:420-425; http://dx.doi.org/10.1289/ehp.1509755.

Nanostructured metal oxides: promise opportunity and challenge to develop clinically useful 99Mo/99mTc generators using (n, gamma)99Mo

International Nuclear Information System (INIS)

Dash, Ashutosh

2014-01-01

The role of 99m Tc diagnostic nuclear medicine needs hardly to be reiterated. Today, it is the most widely used radionuclide for single photon emission computed tomography (SPECT) imaging procedures. The current strategy of availing 99m Tc is ensured from column chromatographic 99 Mo/ 99m Tc generators using a bed of acidic alumina. While the column chromatographic 99 Mo/ 99m Tc generator constitute a successful exemplar of availing 99m Tc, the limited capacity of alumina (2-20 mg Mo per g of alumina) for taking up molybdate ions necessitates the use of 99 Mo of the highest specific activity available, as can be found in fission produced 99 Mo (F 99 Mo). In order to reduce dependence of F 99 Mo, the scope of using low specific activity (n,γ) 99 Mo along with high capacity adsorbent is an interesting prospect. In this context, the scope of using nanomaterials as a viable adsorbent seemed attractive by virtue of their huge surface to volume ratios, altered physical properties, tailored surface chemistry, favorable adsorption characteristics, and enhanced surface reactivity resulting from the nanoscale dimensions. This emerging class of adsorbent represents an innovative paradigm and is expected to play an important role in the development of 99 Mo/ 99m Tc generators adaptable to the existing and foreseeable demands. This talk outlines a critical assessment on the role of nanostructured metal oxides, recent developments, the contemporary status, and key challenges and apertures to the near future. (author)

Imaging endocarditis with Tc-99m-labeled antibody--an experimental study: concise communication

Energy Technology Data Exchange (ETDEWEB)

Wong, D.W.; Dhawan, V.K.; Tanaka, T.; Mishkin, F.S.; Reese, I.C.; Thadepalli, H.

1982-03-01

The sensitivity and specificity of Tc-99m-labeled antibacterial antibody (Tc-99m Ab) for detecting bacterial endocarditis were evaluated in an experimental model. Rabbit-produced antistaphylococcal antibody was extracted using Rivanol and chemically labeled with Tc-99m. This Tc-99m Ab was injected intravenously in New Zealand rabbits 24 hr after producing Staphylococcus aureus endocarditis of the aortic valve. Imaging and tissue analyses were performed on the following day. All 11 animals developed S. aureus aortic-valve vegetations and showed increased uptake of Tc-99m Ab at the aortic valve, 118 times higher than at the uninfected tricuspid valve. Although high hepatic radioactivity and anatomic uncertainties interfered with in vivo delineation of these lesions, images of the excised hearts showed all affected valves. Two rabbits inoculated with Escherichia coli did not develop endocarditis and had little uptake of Tc-99m Ab, while six rabbits with enterococcal endocarditis had no uptake of the Tc-99m Ab in their vegetations. The findings suggest potential value of Tc-99m Ab on the rapid diagnosis of endocarditis.

Imaging endocarditis with Tc-99m-labeled antibody--an experimental study: concise communication

International Nuclear Information System (INIS)

Wong, D.W.; Dhawan, V.K.; Tanaka, T.; Mishkin, F.S.; Reese, I.C.; Thadepalli, H.

1982-01-01

The sensitivity and specificity of Tc-99m-labeled antibacterial antibody (Tc-99m Ab) for detecting bacterial endocarditis were evaluated in an experimental model. Rabbit-produced antistaphylococcal antibody was extracted using Rivanol and chemically labeled with Tc-99m. This Tc-99m Ab was injected intravenously in New Zealand rabbits 24 hr after producing Staphylococcus aureus endocarditis of the aortic valve. Imaging and tissue analyses were performed on the following day. All 11 animals developed S. aureus aortic-valve vegetations and showed increased uptake of Tc-99m Ab at the aortic valve, 118 times higher than at the uninfected tricuspid valve. Although high hepatic radioactivity and anatomic uncertainties interfered with in vivo delineation of these lesions, images of the excised hearts showed all affected valves. Two rabbits inoculated with Escherichia coli did not develop endocarditis and had little uptake of Tc-99m Ab, while six rabbits with enterococcal endocarditis had no uptake of the Tc-99m Ab in their vegetations. The findings suggest potential value of Tc-99m Ab on the rapid diagnosis of endocarditis

Decay of 99Mo

International Nuclear Information System (INIS)

Dickens, J.K.; Love, T.A.

1976-01-01

Relative intensities for K x-rays and gamma rays emanating from 99 Mo in equilibrium with its 99 Tc* daughter have been measured using several Ge photon detectors. Combining these intensities with an evaluated set of electron-conversion coefficients has provided a set of absolute intensities for the observed gamma rays. The absolute intensity for the dominant 140.5-keV gamma ray in 99 Tc was determined to be 90.7 +- 0.6/100 99 Mo disintegrations for 99 Mo decay in equilibrium with decay of the 99 Tc* daughter

Techneticum-99m pharmaceuticals. Preparation and quality control in nuclear medicine

International Nuclear Information System (INIS)

Zolle, I.

2007-01-01

Radioactive drug development is a multi-disciplinary task, therefore, in a concerted effort, dedicated scientists and experts from different fields of specialisation have contributed to this book. It is presented in two sections. Section 1 contains basic principles and methods used for analysis, information on the chemistry of technetium and on radiopharmaceuticals labelled with technetium-99m, the characteristics of the 99 Mo/99mTc-generator, of 'kits' and formulations for in-vitro labelling, and special safety aspects for in-vivo labelling of blood cells. Section 2 contains monographs of 99mTc-radiopharmaceuticals used in nuclear medicine. Each monograph includes information on the chemistry, formulation, commercial products and trade names, factors affecting in-vivo performance, clinical information on pharmacokinetics, as well as details concerning the clinical application and the radiation dose to patients. (orig.)

Polybrominated diphenyl ethers (PBDEs) in US meat and poultry: 2012-13 levels, trends and estimated consumer exposures.

Science.gov (United States)

Lupton, Sara J; Hakk, Heldur

2017-09-01

Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants whose use has contaminated foods and caused subsequent human exposures. To address the issue of possible human exposure, samples from a 2012-13 US meat and poultry (beef, pork, chicken, turkey) study were analysed for seven PBDEs. The mean summed concentrations of the seven BDE congeners (ΣPBDE) from beef, pork, chicken and turkey were 0.40, 0.36, 0.19, and 0.76 ng g -1 lipid weight (lw). The range of ΣPBDEs for all meat classes was 0.01-15.78 ng g -1 lw. A comparison of this study with a 2007-08 study revealed a decline in the median ΣPBDEs for all four meat classes, a reduction of 25.9% to 70.0%, with pork, chicken and turkey PBDE residues being statistically lower relative to the 2007-08 study. BDEs 47 and 99 contributed the most to the ΣPBDE concentrations, indicating likely animal exposures to the penta-BDE formulation. Based on the reported data an estimate of US consumer daily intake of PBDEs from meat and poultry was 6.42 ng day -1 .

Distribution of polybrominated diphenyl ethers in sediments of the Pearl River Delta and adjacent South China Sea.

Science.gov (United States)

Mai, Bixian; Chen, Shejun; Luo, Xiaojun; Chen, Laiguo; Yang, Qingshu; Sheng, Guoying; Peng, Pingan; Fu, Jiamo; Zeng, Eddy Y

2005-05-15

Spatial and temporal distributions of polybrominated diphenyl ethers (PBDEs) in sediments of the Pearl River Delta (PRD) and adjacent South China Sea (SCS) of southern China were examined. A total of 66 surface sediment samples were collected and analyzed to determine the concentrations of 10 PBDE congeners (BDE-28, -47, -66, -100, -99, -154, -153, -138, -183, and -209). The concentrations of BDE-209 and SigmaPBDEs (defined as the sum of all targeted PBDE congeners except for BDE-209) ranged from 0.4 to 7340 and from 0.04 to 94.7 ng/g, respectively. The SigmaPBDEs concentrations were mostly transportation. The PBDE patterns in the SCS and Pearl River Estuary sediments were similar to those in sediments of the Zhujiang and Dongjiang Rivers, reflecting the widespread influence from local inputs. Analyses of two short sediment cores collected from the Pearl River Estuary showed that concentrations of BDE-209 rapidly increased in the upper layers of both cores, coincident with the growth of the electronics manufacturing capacities in the PRD region. The major sources of PBDEs were probably waste discharges from the cities of Guangzhou, Dongguan, and Shenzhen, the three fastest growing urban centers in the PRD.

Occurrence and levels of polybrominated diphenyl ethers (PBDEs) in house dust and hair samples from Northern Poland; an assessment of human exposure.

Science.gov (United States)

Król, Sylwia; Namieśnik, Jacek; Zabiegała, Bożena

2014-09-01

Polybrominated diphenyl ethers (PBDEs) are among most ubiquitous compounds to be found in indoor environment and ingestion of household dust is considered an important route of exposure to PBDEs, especially in toddlers and young children. The present work reported concentration levels of PBDE congeners (PBDE-28, -47, -99, -100, -153, -154, -183 and -209) in hair and dust samples from selected households from Northern Poland. The concentrations of PBDEs in dust ranged from human hair. PBDE-209 was reported the dominating congener. Two separated exposure scenarios (mean and 95th percentile) were used to provide a comprehensive overview of possible risks arising from ingestion of household dust. The estimated exposure to ∑PBDEs via ingestion of household dust varied from 21 to 92ngd(-1) in toddlers and from 3.7 to 20ngd(-1) in adults. By comparison of correlation between the concentrations of PBDEs in paired hair and dust samples the present work also investigated the possibility of use of hair for reflecting the actual exposure to PBDEs in humans. Finally the possible uncertainties associated with exposure assessment were investigated in the present study. Copyright © 2014 Elsevier Ltd. All rights reserved.

Expression analysis of cellulose synthase and main cytoskeletal protein genes in flax (Linum usitatissimum L.).

Science.gov (United States)

Galinousky, Dmitry; Padvitski, Tsimafei; Bayer, Galina; Pirko, Yaroslav; Pydiura, Nikolay; Anisimova, Natallia; Nikitinskaya, Tatyana; Khotyleva, Liubov; Yemets, Alla; Kilchevsky, Aleksandr; Blume, Yaroslav

2017-08-09

Fiber flax is an important source of natural fiber and a comprehensive model for the plant fiber biogenesis studies. Cellulose-synthase (CesA) and cytoskeletal genes are known to be important for the cell wall biogenesis in general and for the biogenesis of flax fibers in particular. Currently, knowledge about activity of these genes during the plant growth is limited. In this study, we have investigated flax fiber biogenesis by measuring expression of CesA and cytoskeletal genes at two stages of the flax development (seedlings and stems at the rapid growth stage) in several flax subspecies (elongatum, mediterraneum, crepitans). RT-qPCR has been used to quantify the expression of LusСesA1, LusСesA4, LusСesA7, LusСesA6, Actin, and α-Tubulin genes in plant samples. We report that CesA genes responsible for the secondary cell wall synthesis (LusCesA4, LusCesA7) have different expression pattern compared with CesA genes responsible for the primary cell wall synthesis (LusCesA1, LusCesA6): an average expression of LusCesA4 and LusCesA7 genes is relatively high in seedlings and further increases in stems at the rapid growth stage, whereas an average expression of LusCesA1 and LusCesA6 genes decreases. Interestingly, LusCesA1 is the only studied gene with different expression dynamics between the flax subspecies: its expression decreases by 5.2-10.7 folds in elongatum and mediterraneum but does not change in crepitans subspecies when the rapid growth stage and seedlings are compared. The expression of cytoskeleton genes (coding actin and α-tubulin) is relatively stable and significantly higher than the expression of cellulose-synthase genes in all the studied samples. © 2017 International Federation for Cell Biology.

Comparative study of {sup 99}Mo/{sup 99m}Tc generators at base of synthesized gels starting from activation and fission {sup 99}Mo; Estudio comparativo de generadores {sup 99}Mo/{sup 99m}Tc a base de geles sintetizados a partir de {sup 99}Mo de activacion y de fision

Energy Technology Data Exchange (ETDEWEB)

Lopez M, I Z [UAEM, Paseo Colon esq. Paseo Tollocan, 50120 Toluca, Estado de Mexico (Mexico); Monroy G, F; Rivero G, T; Rojas N, P [ININ, Carretera Mexico -Toluca S/N, 52045 La Marquesa Ocoyoacac, Estado de Mexico (Mexico)

2007-07-01

The {sup 99m}Tc is used for diagnostic and therapy. It is produced starting from {sup 99}Mo, absorbed in chromatographic columns, loaded with alumina that absorb only 0.2% of {sup 99}Mo with high specific activities of {sup 99}Mo, obtained from the {sup 235}U fission. Given these conditions and limitations, new preparation procedures of {sup 99}Mo/{sup 99m}Tc generators, its have been developed, using zirconium molybdates gels that incorporates until 30% of {sup 99}Mo, conserve similar characteristics of quality and purity that the traditional generator. The radiochemical characteristics of the {sup 99m}Tc elution, depend strongly on the gel preparation conditions. In particular, the present work has by object to determine the influence of the {sup 99}Mo used type, fission or activation product, during the gels synthesis, as well as the used air flow for the agitation in the gels preparation and its influence in the {sup 99}Mo/{sup 99m}Tc generators quality. When diminishing the flow of agitation air the efficiency it increases and in the radionuclide purity of the eluates and when using {sup 99}Mo from fission for the gels production it increases in an important way the elutriation efficiency, the radiochemical and radionuclide purity of the {sup 99m}Tc eluates. (Author)

Beta-actin deficiency with oxidative posttranslational modifications in Rett syndrome erythrocytes: insights into an altered cytoskeletal organization.

Directory of Open Access Journals (Sweden)

Alessio Cortelazzo

Full Text Available Beta-actin, a critical player in cellular functions ranging from cell motility and the maintenance of cell shape to transcription regulation, was evaluated in the erythrocyte membranes from patients with typical Rett syndrome (RTT and methyl CpG binding protein 2 (MECP2 gene mutations. RTT, affecting almost exclusively females with an average frequency of 1∶10,000 female live births, is considered the second commonest cause of severe cognitive impairment in the female gender. Evaluation of beta-actin was carried out in a comparative cohort study on red blood cells (RBCs, drawn from healthy control subjects and RTT patients using mass spectrometry-based quantitative analysis. We observed a decreased expression of the beta-actin isoforms (relative fold changes for spots 1, 2 and 3: -1.82±0.15, -2.15±0.06, and -2.59±0.48, respectively in pathological RBCs. The results were validated by western blotting and immunofluorescence microscopy. In addition, beta-actin from RTT patients also showed a dramatic increase in oxidative posttranslational modifications (PTMs as the result of its binding with the lipid peroxidation product 4-hydroxy-2-nonenal (4-HNE. Our findings demonstrate, for the first time, a beta-actin down-regulation and oxidative PTMs for RBCs of RTT patients, thus indicating an altered cytoskeletal organization.

Results of regular study on radionuclidic purity of sup(99m)Tc obtained from 99Mo-sup(99m)Tc generators

International Nuclear Information System (INIS)

Vlcek, J.; Rohacek, J.; Husak, V.

1979-01-01

A total of 39 sup(99m)Tc eluates obtained from 9 99 Mo-sup(99m)Tc generators delivered by The Radiochemical Centre Amersham during one year was studied with regard to their radionuclide purity. Using a Ge(Li) spectrometer the contaminants 60 Co, 103 Ru, 131 I, 134 Cs, 140 La and 188 Re were found in sup(99m)Tc-eluates with average levels ranging from 2.9 x 10 -3 to 2.8 x 10 -1 per cent of sup(99m)Tc activity. The additional total body absorbed dose caused by these contaminants, as calculated from their average content in sup(99m)Tc eluates, was less than 1% of the dose due to sup(99m)Tc pertechnetate. (orig.) 891 MG/orig. 892 CS [de

Radionuclidic contamination of 99Mo, 131I and 103Ru in the eluate of 99Mo-99mTc chromatographic generator: comparision on fission produced 99Mo from RPC, Nordio and ARI

International Nuclear Information System (INIS)

Soenarjo, Sunarhadijoso; Gunawan, Adang Hardi

1996-01-01

The 99 Mo- 99m Tc Chromatographic generators is the most popular system to provide 99m Tc medical radioisotope. Radioisotope Production Centre (RPC)- BATAN has routinely produced the generator loaded with 99 Mo prepared by 235 U fission. By using fission produced 99 Mo, the resulting 99m Tc is potentially contaminated by other fission products which are difficult to eliminate completely. In order to study the characteristic of the generator and radionuclidic impurity pattern of the 99m Tc eluates, an evaluation of gamma spectrometric determination has been carried out. The bulk solutions of 99 Mo produced by RPC BATAN (Indonesia), Nordion (Canada) and ARI (Australia) were loaded to generators manufactured between July 1993 to May 1994. The saline-eluate 99m Tc, in a total volume of 10 ml each, was subjected to gamma spectrometric determination. The radiation of 99m Tc was eliminated by lead shield of 0.6913 cm thickness. The 99m Tc yield fluctuation from 28 generators indicated that the characteristics of the generator columns were very good. The 99m Tc eluates were consistently contaminated by 99 Mo, 131 I and 103 Ru, although the contamination level in all cases did not exceed the maximum permissible levels. The fluctuation of radionuclidic impurities were probably caused by variation in the irradiation parameter or by variation in the 99 Mo separation methods. (author), 23 refs, 1 tab, 3 figs

'99Mo/99mTc Generator Based on High Radionuclidic Pure Zirconium Molybdate Gel

International Nuclear Information System (INIS)

Amin, M.; Mostafa, M.; El-Amir, M.A.; El-Absy, M.A.; Mohamed, O.I.; Farag, A.B.

2014-01-01

99 Mo / 99 mTc radioisotope generator was prepared using in-situ precipitated zirconium molybdate chromatographic column. Zirconium molybdate gel matrix was synthesized by precipitation of neutron activation molybdenum-99 from its solution after variety purification processes to prevent contamination of the 99m Tc eluate with cross-contaminants. Greeter than 82.7 ± 0.4 % of the generated 99m Tc was immediately and reproducible eluted by passing 10 ml 0.9 % NaCl solution through the 1 g zirconium molybdate- 99 Mo column matrix at a flow rate of 0.5 ml / min and room temperature with high chemical, radionuclide ( ≥ 99.9 % 99m Tc) and radiochemical purity ( ≥ 97.7 % % as 99 mTcO 4 - ) with ph value suitable for medical uses.

Magnesium-Molybate Compounds as Matrix for 99Mo/99mTc Generators

Directory of Open Access Journals (Sweden)

Fabiola Monroy-Guzman

2011-01-01

Full Text Available This work reports the preparation of a 99mTc generator based on conversion of 99Mo produced by neutron irradiation, into insoluble magnesium 99Mo-molybdates compounds as matrix. The effect of magnesium salt types and concentration, Mg:Mo molar ratios, pH of molybdate solutions, eluate volume as well as the addition order of molybdate and magnesium solutions’ influences on the final 99mTc were evaluated. Polymetalates and polymolybdates salts either crystallized or amorphous were obtained depending on the magnesium salt and Mg:Mo molar ratio used in matrix preparation. 99Mo/99mTc generator production based on magnesium-99Mo molybdate compounds allow reduction of preparation time and eliminates the use of specialized installations. The best generator performances were attained using matrices prepared from 0.1 mol/L MgCl2·6H2O solutions, ammonium molybdate solutions at pH 7 and at a Mg:Mo molar ratio of 1:1.

Radionuclide Basics: Technetium-99

Science.gov (United States)

Technetium-99 (chemical symbol Tc-99) is a silver-gray, radioactive metal. It occurs naturally in very small amounts in the earth's crust, but is primarily man-made. Technetium-99m is a short-lived form of Tc-99 that is used as a medical diagnostic tool.

Recent global crisis in 99Mo production and supplies: analysis and lessons

International Nuclear Information System (INIS)

Ramamoorthy, Natesan; Ed Bradley; Adelfang, Pablo; )

2011-01-01

The radioisotope 99m Tc is a vital need for diagnostic functional imaging of organs and physiologic processes in nuclear medicine centres and hospitals all over the world. 99m Tc (6 h) is obtained from the radioactive (beta) decay of 99 Mo (66 h) and is generally availed at the user end in hospitals or radiopharmacies from a 99 Mo- 99m Tc generator, and therefore reliable weekly availability of 99 Mo of very high specific activity is essential for sustainable supplies of 99m Tc. Over the past several decades, the commercial availability of 99 Mo (mostly fission-produced) from corporate sources has been satisfactory. However, from around the end of 2007, the production and supplies of 99 Mo were severely and repeatedly affected causing worldwide concerns and led to calls for international efforts to address the security of supplies of 99 Mo and 99m Tc. Various initiatives and analytical reviews during the past two years, including at the IAEA and OECD-NEA, have revealed a number of issues and lessons learnt. Research reactor managers and their governments serving 99 Mo- 99m Tc industry have faced several challenges, technological, regulatory and economical among others, apart from the fact that these reactors are not dedicated to isotopes production. Furthermore, towards long term security of 99 Mo supplies, switch over to using LEU targets and establishing some additional processing capacity need to be addressed. Several alternative non-HEU technologies for producing 99 Mo and 99m Tc are also under consideration, including through non-fission and non-reactor based methods. The article will draw analytical conclusions and recommendations based on the available professional knowledge and experience in the field as well as from the findings reported in the recent documents and in meetings including that of the IAEA and OECD-NEA. (author)

99Mo-99mTc generator - study of their performance and quality

International Nuclear Information System (INIS)

Acar, M.E.D.

1987-01-01

In this work the performance of the 99 Mo - 99m Tc generators produced at IPEN-CNEN/SP as well as the quality of the eluted solutions were analysed. The following parameters were studied: elution efficiency, chemical radiochemical, radionuclidic and microbiological purities and pH of the eluates. The 99m Tc yield ranged from 84,7 to 98,5%. The radioactivity due to the pertechnetate ion in the studied solutions was higher than 97,5%. The aluminium content in eluates, determined by spectrophotometry, was lower than 2,5 μg/ml and the pH of the solutions between 4,5 and 5,1. Radioactive impurities of the order of 10 -3 KBq 99 Mc/MBq 99m Tc and 10 -5 KBq 131 I/MBq 99m Tc were found in the eluates at the time of elution. Other γ emitting radioactive impurities were order of 10 -3 KBq/MBq 99m Tc. The eluates were sterile and pyrogen-free. From the results obtained in this work one can state that the IPEN-TEC generator is a reliable source of good quality 99m Tc-pertechnetate. (author) [pt

99Mo production by 100Mo(n,2n)99Mo using accelerator neutrons

International Nuclear Information System (INIS)

Sato, Nozomi; Kawabata, Masako; Nagai, Yasuki; Hashimoto, Kazuyuki; Hatsukawa, Yuichi; Saeki, Hideya; Motoishi, Shoji; Kin, Tadahiro; Konno, Chikara; Ochiai, Kentaro; Takakura, Kosuke; Minato, Futoshi; Iwamoto, Osamu; Iwamoto, Nobuyuki; Hashimoto, Shintaro

2013-01-01

We proposed a new route to produce a medical radioisotope 99 Mo by the 100 Mo(n,2n) 99 Mo reaction using accelerator neutrons. A high-quality 99 Mo with a minimum level of radioactive waste can be obtained by the proposed reaction. The decay product of 99 Mo, 99m Tc, is separated from 99 Mo by the sublimation method. The proposed route could bring a major breakthrough in the solution of ensuring a constant and reliable supply of 99 Mo. (author)

Present status of Mo-99/Tc-99m generator in Thailand

International Nuclear Information System (INIS)

Khongpetch, Pranom

2007-01-01

Isotop Production Program, Office of Atoms for Peace had produced technetium-99m by MEK extraction of Mo-99 obtained from (n,γ) reaction in TRIGA Mark III reactor and supplied to nuclear medicine centers in Bangkok from 1980 to 1997. Because of the difficulty to meet the increased demand and limitation of reactor operation, the production of technetium-99m was stopped in 1997. Presently, there are 21 nuclear medicine centers with 25 SPECT, 7 gamma camera and 3 PET. All nuclear medicine centers are currently using imported Tc-99m generator. (author)

Quality control studies of 99Mo used in 99Mo/99mTc generators produced at IPEN/CNEN-SP, Brazil

International Nuclear Information System (INIS)

Said, Daphne S.; Brambilla, Tania P.; Matsuda, Margareth M.N.; Osso Junior, Joao A.

2015-01-01

99m Tc is the most used radionuclide in nuclear medicine. In Brazil, the 99 Mo/ 99m Tc generators are produced exclusively by the Center of Radiopharmacy at IPEN-CNEN/SP, by importing 99 Mo from different suppliers. 99 Mo (t 1/2 = 66 h) is a fission product of 235 U, therefore, it can be accompanied by several radioisotopes that are highly prejudicial for human health, demanding a strict quality control of this product for generators safe use. The European Pharmacopoeia established some parameters and limits that evaluate the quality of the solution of sodium [ 99 Mo]molybdate, that is used as raw material for generator's production. The European Pharmacopoeia also recommends some analytical methods to perform these evaluations, however, it has been observed difficulties on the implementation of these methods by the generator's producers. These difficulties are probably related to the lack of practicability of the proposed methods and the extensive list of utilized reagents. In this work some procedures of the European Pharmacopoeia's quality control method for 99 Mo were evaluated. Different types of solid phase exchanger cartridges were tested for retention of 99 Mo in 3 different conditions. Cartridges that presented percentages of retention higher than 90% were also tested for separation of 99 Mo from possible contaminants (Ru e Te). The results shown that solid phase exchanger cartridges that presented percentages of retention of Mo higher than 90% also presented significant percentages of retention of Ru and Te. An alternative method for separation of 99 Mo from 131 I (other contaminant) are also proposed. (author)

Cytoskeletal remodeling of connective tissue fibroblasts in response to static stretch is dependent on matrix material properties

Science.gov (United States)

Abbott, Rosalyn D; Koptiuch, Cathryn; Iatridis, James C; Howe, Alan K; Badger, Gary J; Langevin, Helene M

2012-01-01

In areolar “loose” connective tissue, fibroblasts remodel their cytoskeleton within minutes in response to static stretch resulting in increased cell body cross-sectional area that relaxes the tissue to a lower state of resting tension. It remains unknown whether the loosely arranged collagen matrix, characteristic of areolar connective tissue, is required for this cytoskeletal response to occur. The purpose of this study was to evaluate cytoskeletal remodeling of fibroblasts in and dissociated from areolar and dense connective tissue in response to 2 hours of static stretch in both native tissue and collagen gels of varying crosslinking. Rheometric testing indicated that the areolar connective tissue had a lower dynamic modulus and was more viscous than the dense connective tissue. In response to stretch, cells within the more compliant areolar connective tissue adopted a large “sheet-like” morphology that was in contrast to the smaller dendritic morphology in the dense connective tissue. By adjusting the in vitro collagen crosslinking, and the resulting dynamic modulus, it was demonstrated that cells dissociated from dense connective tissue are capable of responding when seeded into a compliant matrix, while cells dissociated from areolar connective tissue can lose their ability to respond when their matrix becomes stiffer. This set of experiments indicated stretch-induced fibroblast expansion was dependent on the distinct matrix material properties of areolar connective tissues as opposed to the cells’ tissue of origin. These results also suggest that disease and pathological processes with increased crosslinks, such as diabetes and fibrosis, could impair fibroblast responsiveness in connective tissues. PMID:22552950

49 CFR 1242.33 - Other expenses and casualties and insurance (accounts XX-17-99, XX-18-99, XX-19-99, 50-17-00, 50...

Science.gov (United States)

2010-10-01

... (accounts XX-17-99, XX-18-99, XX-19-99, 50-17-00, 50-18-00, and 50-19-00). 1242.33 Section 1242.33....33 Other expenses and casualties and insurance (accounts XX-17-99, XX-18-99, XX-19-99, 50-17-00, 50... separation of administrative—other (account XX-19-06). Operating Expenses—Equipment locomotives ...

Cytoskeletal Linker Protein Dystonin Is Not Critical to Terminal Oligodendrocyte Differentiation or CNS Myelination.

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Samantha F Kornfeld

Full Text Available Oligodendrocyte differentiation and central nervous system myelination require massive reorganization of the oligodendrocyte cytoskeleton. Loss of specific actin- and tubulin-organizing factors can lead to impaired morphological and/or molecular differentiation of oligodendrocytes, resulting in a subsequent loss of myelination. Dystonin is a cytoskeletal linker protein with both actin- and tubulin-binding domains. Loss of function of this protein results in a sensory neuropathy called Hereditary Sensory Autonomic Neuropathy VI in humans and dystonia musculorum in mice. This disease presents with severe ataxia, dystonic muscle and is ultimately fatal early in life. While loss of the neuronal isoforms of dystonin primarily leads to sensory neuron degeneration, it has also been shown that peripheral myelination is compromised due to intrinsic Schwann cell differentiation abnormalities. The role of this cytoskeletal linker in oligodendrocytes, however, remains unclear. We sought to determine the effects of the loss of neuronal dystonin on oligodendrocyte differentiation and central myelination. To address this, primary oligodendrocytes were isolated from a severe model of dystonia musculorum, Dstdt-27J, and assessed for morphological and molecular differentiation capacity. No defects could be discerned in the differentiation of Dstdt-27J oligodendrocytes relative to oligodendrocytes from wild-type littermates. Survival was also compared between Dstdt-27J and wild-type oligodendrocytes, revealing no significant difference. Using a recently developed migration assay, we further analysed the ability of primary oligodendrocyte progenitor cell motility, and found that Dstdt-27J oligodendrocyte progenitor cells were able to migrate normally. Finally, in vivo analysis of oligodendrocyte myelination was done in phenotype-stage optic nerve, cerebral cortex and spinal cord. The density of myelinated axons and g-ratios of Dstdt-27J optic nerves was normal, as

Chemical aspects of labeling sucralfate with 99mTcO4

International Nuclear Information System (INIS)

Billinghurst, M.W.; Abrams, D.N.; Lawson, M.S.

1989-01-01

Two formulations of [ 99m Tc]sucralfate have been used to image gastric and duodenal ulcers and inflammatory bowel disease. One formulation is a complexation of [ 99m Tc]HSA with sucralfate. The second is prepared by directly labeling sucralfate with [ 99m Tc]pertechnetate in the presence of stannous ion. An in vitro study of the factors affecting the production and stability of these labeled sucralfate preparations was conducted. Both formulations were stable at the acidic pH likely encountered in the stomach. However, at pH greater than 6 the albumin-sucralfate complex began to dissociate while directly labeled sucralfate was stable to a pH of 9. Conversely it was shown that directly labeled sucralfate was more susceptible to loss of 99m Tc to other chelating species. Sucralfate complexed with [ 99m Tc]HSA was radiochemically stable up to a specific activity of 26 GBq (700 mCi) per gram while directly labeled sucralfate showed decreased 24-hr stability at specific activities greater than 837 mCi (31 GBq) per gram

Technetium-99m human immunoglobulin scintigraphy in patients with adhesive capsulitis. A correlative study with bone scintigraphy

International Nuclear Information System (INIS)

Senocak, O.; Degirmenci, B.; Ozdogan, O.; Akalin, E.; Arslan, G.; Kaner, B.; Tasci, C.; Peker, O.

2002-01-01

Adhesive capsulitis (AC) is a disorder that is characterized by shoulder pain and progressive limitation of both active and passive shoulder motion. Although the underlying pathological mechanisms of the disease are not well understood, the inflammatory reactions depending on the stage have been demonstrated histologically. The purpose of the study is to investigate the inflammatory changes that can be demonstrated with Tc-99m HIG in AC, and to determine the presence of correlations between scintigraphic findings and the clinical assessment. Twenty-one patients (12 females and 9 males) with a mean age of 50.57±8.49 were included in the study. AC was diagnosed according to recognized criteria. The planar X-ray images of the affected shoulders of all patients were normal. The patients were evaluated with the Constant Scoring System, and the functional and pain assessment parts of the American Shoulder and Elbow Surgeons' Form (ASES). Three phase bone scans and Tc-99m HIG scintigraphy were performed at least two days apart. Bone scan and Tc-99m HIG scintigraphy were evaluated visually and HIG uptake was evaluated in comparison with the contralateral normal shoulder. Bone scan demonstrated hypervascularity in 9 of the 21 patients (43%), whereas increased osteoblastic activity was detected in 19 (90%) in the affected shoulder. Tc-99m, HIG uptake was positive in 12 (57%), and negative in 9 (43%) patients. All patients with increased Tc-99m HIG accumulation in the affected shoulder, also had increased osteoblastic activity on Tc-99m bone scintigraphy. A significant correlation was found between HIG uptake and constant, functional and pain scores. The difference between these scores was also statistically significant in patients with HIG positive and negative uptake. This study indicates that there is a good correlation between Tc-99m HIG scan findings and clinical scores. Tc-99m HIG accumulation in the affected shoulder may be related to continuing inflammatory reaction

Homogeneous SLOWPOKE reactors for Mo-99/Tc-99m production in North America

Energy Technology Data Exchange (ETDEWEB)

Hilborn, J.W., E-mail: hilbovanw@sympatico.ca [Deep River, Ontario (Canada); Bonin, H.W. [Royal Military College of Canada, Kingston, Ontario (Canada)

2014-07-01

The 15 month shutdown of NRU in 2009 - 2010 caused an overall isotope shortage of approximately 30%; and in North America, the annual Tc-99m demand decreased from an estimated 20 million unit doses to about 15 million unit doses. Mo-99/Tc-99m is produced from HEU targets, irradiated in NRU for 11 days, and after chemical removal of uranium it is shipped to Nordion in Kanata, Ontario. Nordion further purifies the material and sends it to Lantheus Medical Imaging in the USA for manufacture of Mo-99 generators, which are then distributed to hundreds of hospital radiopharmacies throughout North America. One other American company, Covidien, manufactures and distributes Mo-99 generators like Lantheus, but they import bulk Mo-99 from Europe or South Africa. At the hospitals, Tc-99m is chemically extracted daily from the Mo-99 generators and loaded into syringes for immediate clinical use. Fortuitously, the 66 hour half-life of Mo-99 allows the replenishment of Tc-99m in the generator over a growth period of about 20 hours; and a generator can be 'milked' daily for up to two weeks. A more efficient model is the direct production and distribution of Tc-99m unit doses to regional hospitals from 10 'industrial' radiopharmacies located at existing licensed reactor sites in North America. A 20 kW homogeneous SLOWPOKE reactor at each site would deliver 15 litres of irradiated uranyl sulphate fuel solution daily to industrial-scale hot cells for extraction of Mo-99, which would be incorporated in large Mo-99/Tc-99m generators for extraction of Tc-99m five days a week; and the Low Enriched Uranium (LEU) would be recycled. Each automated hot-cell facility would be designed to load up to 7,000 Tc-99m syringes daily, for courier delivery to all of the Nuclear Medicine hospitals within a 3 hour average range by road transport. Typically, the delivered doses would be in the range 10 to 30 mCi. Assuming an average unit dose of 25 mCi at the hospital and 5 x 52

Preparing for Molybdenum-99 Production In Malaysia [Country report: Malaysia

International Nuclear Information System (INIS)

Dahalan, Rehir; Masood, Zarina; Zulkifli, Mohd Hashim; Yusof, Mohd Abd Wahab

2015-01-01

The research reactor at Nuclear Malaysia, which has been in operation since June 1982, has a maximum flux of 1x10 13 n/cm 2 /s at its central position, has been utilized in production of neutron activated molybdenum-99 ( 99 Mo) and may be suitable for the new initiative for producing fission 99 Mo from low enriched uranium (LEU) targets if an upgrade involving its power and neutron flux were done. Currently, there is no fission 99 Mo production in place in Malaysia; however, there is an existing weekly 99 Mo/ 99m Tc generator production utilizing imported fission 99 Mo. Malaysia’s current demand for fission 99 Mo is relatively small but is still affected by the recent supply turmoil. At the request of the Malaysia Nuclear Agency, the IAEA organized a fact-finding mission to assess currently available infrastructure against that necessary to produce fission 99 Mo sufficient for domestic needs or additionally to contribute to regional fission 99 Mo supply security. During the mission, 99 Mo production from LEU and the alternative neutron activation method were considered. Taking into consideration sufficient upgrade of the current research reactor power and neutron flux, neutron activation could satisfy current national demand but offers little excess capacity to accommodate future growth or participation in the regional 99 Mo market. Also at a higher reactor power and neutron flux, LEU fission based technologies could produce adequate quantities for domestic and regional supply, but require significantly greater resource commitment than neutron activation production technologies particularly with respect to the management and ultimate disposition of all waste streams. In addition to the completion of the reactor power and flux upgrade, revising the operating mode to continuous operation is a prerequisite to fission 99 Mo production together with additional equipment for handling and transferring higher radiation dose target capsules from the reactor to the hot

99Mo production for using in the nuclear medicine in 99mTc generators

International Nuclear Information System (INIS)

Kurenkov, N.V.; Chuvilin, D.Yu.

1999-01-01

The review of methods and advanced technologies for obtaining 99 Mo in nuclear reactors is presented. The 99 Mo isotope is used for preparing the 99m Tc generators, widely applied in nuclear medicine. The reactor method for obtaining 99 Mo is based on the 98 Mo(n, γ) 99 Mo radiation capture reaction and 235 U fission reaction under the effect of the 235 U (n, f) 99 Mo reaction. The results of studies on obtaining 99 Mo on the charged particles accelerators, mainly, on the proton beam and under the effect of photonuclear reaction is also described. The data on the 99 Mo real consumption and forecast for its application in different regions of the world from 1994 up to 2006 are presented [ru

Development of 99mTc extraction techniques from 99Mo by (n,γ) reaction

International Nuclear Information System (INIS)

Kimura, Akihiro; Hori, Naohiko; Tsuchiya, Kunihiko; Ishihara, Masahiro; Yamabayashi, Hisamichi; Tanase, Masakazu; Fujisaki, Saburo; Sato, Yuichi

2010-11-01

Investigation of production method of 99 Mo by (n, γ) reaction, where the processing is relatively simple and generating less amount of radioactive waste, is conducted in the Neutron Irradiation and Testing Reactor Center. The 99 Mo is adsorbed to highly efficient adsorbent PZC after neutron irradiation and 99m Tc is eluted. However, radioactivity concentration of the 99m Tc solution obtained from PZC column loaded with 99 Mo derived by (n, γ) method is lower than that obtained from alumina column with 99 Mo by (n, f) method due to extremely low specific activity of (n, f) 99 Mo. Therefore, it is necessary to develop technique for increasing the amount of 99 Mo and the 99m Tc solution of high radioactivity concentration (minimum: 1Ci/ cm 3 ). In this study, the preliminary fabrication tests using high density MoO 3 pellets were carried out to increase the production of 99 Mo. The method of concentrating 99m Tc solution through solvent extraction with MEK was investigated and a device for this concentration process was also developed. In the preliminary tests of the MoO 3 pellets, the pellets having high density were successfully fabricated by the SPS method. Additionally, it was ascertained that the pellets can be dissolved with 6M-NaOH solution completely. The test for 99 Mo adsorption followed by 99m Tc elution using PZC was carried out. As the result, amount of Mo adsorbed to 1g-PZC was about 250mg, and 99m Tc yield was about 80%. In the concentration test using Re solution instead of 99m Tc solution, it was ascertained that the concentration efficiency is higher than 80% of the theoretical value. A concentration device for 99m Tc solution could be realized based on the method employed in the present experiments. The outcomes of development of 99m Tc extraction techniques from 99 Mo by (n,γ) reaction was reviewed in this paper, and the contents were presented in the 3rd International Symposium on Material Test Reactors. (author)

14 CFR 99.1 - Applicability.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Applicability. 99.1 Section 99.1... AND GENERAL OPERATING RULES SECURITY CONTROL OF AIR TRAFFIC General § 99.1 Applicability. (a) This... Identification Zone (ADIZ) designated in subpart B. (b) Except for §§ 99.7, 99.13, and 99.15 this subpart does...

Polybrominated diphenyl ethers, perfluorinated alkylated substances, and metals in tile drainage and groundwater following applications of municipal biosolids to agricultural fields.

Science.gov (United States)

Gottschall, N; Topp, E; Edwards, M; Russell, P; Payne, M; Kleywegt, S; Curnoe, W; Lapen, D R

2010-01-15

Polybrominated diphenyl ethers (PBDEs), perfluorinated alkylated substances (PFAS), and metals were monitored in tile drainage and groundwater following liquid (LMB) and dewatered municipal biosolid (DMB) applications to silty-clay loam agricultural field plots. LMB was applied (93,500 L ha(-1)) in late fall 2005 via surface spreading on un-tilled soil (SS(LMB)), and a one-pass aerator-based pre-tillage prior to surface spreading (AerWay SSD) (A). The DMB was applied (8 Mg d wha(-1)) in early summer 2006 on the same plots by injecting DMB beneath the soil surface (DI), and surface spreading on un-tilled soil (SS(DMB)). Key PBDE congeners (BDE-47, -99, -100, -153, -154, -183, -209) comprising 97% of total PBDE in LMB, had maximum tile effluent concentrations ranging from 6 to 320 ng L(-1) during application-induced tile flow. SS(LMB) application-induced tile mass loads for these PBDE congeners were significantly higher than those for control (C) plots (no LMB) (p0.05). PBDE mass loss via tile (0-2h post-application) as a percent of mass applied was approximately 0.04-0.1% and approximately 0.8-1.7% for A and SS(LMB), respectively. Total PBDE loading to soil via LMB and DMB application was 0.0018 and 0.02 kg total PBDE ha(-1)yr(-1), respectively. Total PBDE concentration in soil (0-0.2m) after both applications was 115 ng g(-1)dw, (sampled 599 days and 340 days post LMB and DMB applications respectively). Of all the PFAS compounds, only PFOS (max concentration=17 ng L(-1)) and PFOA (12 ng L(-1)) were found above detectable limits in tile drainage from the application plots. Mass loads of metals in tile for the LMB application-induced tile hydrograph event, and post-application concentrations of metals in groundwater, showed significant (pA>C for tile and SS(LMB) and A>C for groundwater for most results). Following DMB application, no significant differences in metal mass loads in tile were found between SS(DMB) and DI treatments (PBDE/PFAS were not measured). But for

Use of 99mTc from a commercial 99Mo/9mTc generator as yield tracer for the determination of 99Tc at low levels

DEFF Research Database (Denmark)

Hou, Xiaolin; Jensen, Mikael; Nielsen, Sven Poul

2007-01-01

The concentrations of Tc-99 and impurity radionuclides in the Tc-99m tracer solution obtained from a commercial Mo-99/Tc-99m generator were measured by gamma spectrometry and liquid scintillation counting. Mo-99 and Ru-103 were found in the Tc-99m eluate. A simple separation using two extra alumina...... cartridges was investigated to purify the eluate to obtain a suitable Tc-99m tracer with low Tc-99 concentration. The activity ratio of Tc-99/Tc-99m in the prepared Tc-99m solution is lower than 15 x 10(-9), which is higher than the theoretical ratio of less than 10 x 10(-9). The possible reason is discussed....... The Tc-99 in the 20 kBq spiked Tc-99m tracer was found to be less than 0.3mBq, which is lower than the detection limit of the radiometric method used for environmental samples. The purified Tc-99m eluate is used as yield tracer for the determination of low levels of Tc-99 in environmental samples. (c...

Preparation of a gel of zirconium molybdate for use in the generators of 99 Mo - 99m Tc prepared with 99 Mo produced by the 98 Mo(n,γ)99 Mo reaction

International Nuclear Information System (INIS)

Osso Junior, Joao A.; Lima, Ana Lucia V.P.; Silva, Nestor C. da; Nieto, Renata C.; Velosa, Adriana C. de

1998-01-01

IPEN develops a project concerning the preparation of a gel of Zirconium Molybdate for use in the generators of 99 Mo- 99m Tc . 99m Tc is the most used radioisotope in nuclear medicine diagnosis procedures and nowadays the generators are being prepared with imported 99 Mo, produced by 235 U fission. The production of 99 Mo by the 98 Mo(n, γ) 99 Mo reaction is now possible because of the power upgrade of IPEN's IEA-R1 reactor, from 2 to 5 MW. This work describes the preparation method of Zirconium Molybdate gel that will be used in the 99 Mo- 99m Tc generators. The gel is prepared by the chemical reaction between Mo, in Mo O 3 form, and Zr, in Zr O Cl 2 .8H 2 O form. After the reaction, the gel is filtered, dried and cracked with saline solution. The product is then loaded into glass columns for use as 99m Tc generator. The results showed the good quality of the gel prepared at laboratory level and of the generators evaluated. (author)

Preparation of i.v. 99mTc radiopharmaceuticals from spent moly 99Mo

International Nuclear Information System (INIS)

Noronha, O.P.D.

1998-01-01

Full text: Expiry dating is an important quality assurance precept in (radio) pharmacy. There are occasions when for the sake of patient service one may be forced to continue using an over aged source of 99 Mo to generate 99m Tc beyond 7d, especially when there is short/no supply of 99 Mo, (In the early days the expiry date was 3 d or 3 extractions, whichever one was earlier). With the passage of time a few physico-chemical changes (apart from decay) do occur in the 99 Mo/ 99m Tc milieu. The cocktail also begins to contain traces of carried over MEK which is subjected to strong β-, γ irradiation. These impurity (in trace amounts) is soluble in MEK and even, to an extent, in aqueous media. Furthermore, the concentrated impurity tends to seemingly increase in the bulk 99m TcO 4 - since one is compelled to leach TcO 4 - in lower volume of saline. On many occasions we have been constrained to extend the use of 99 Mo beyond 7 - 14 d. Adequate activities were obtained by pooling the previous week's lot of 99 Mo with the current over aged lot. On a few occasions over the past 26 years we have used 99 Mo much beyond 14 d and 2 - 3 occasions for 26 - 28 d (i.e. >10 t 1 /2 of 99 Mo). On each of these occasions the purity of 99m TcO- 4 was ascertained by pharmacopoeial procedures. It was found that despite depleting activities, the purity was not compromised and the trace impurities, even if present, did not cause any interference. We have profitably utilised the bulk TcO- 4 to formulate a variety of i.v. dosage forms of 99m Tc radiodiagnostics. The following strategy was adopted for the patient services - the agents requiring larger activity levels/patients dose were made available in the earlier period, the other during the latter half. It is concluded that pure 99m TcO- 4 can be obtained over the entire useful life-period of 99 Mo, even > 10t l/2

A comparative study of 99Tcm-tetrofosmin and 99Tcm-MIBI myocardial imaging

International Nuclear Information System (INIS)

Zhao Kui; Chen Peng; Zhang Furong; Shen Wenhua

2001-01-01

Objective: To evaluate the value of 99 Tc m -tetrofosmin myocardial imaging for detecting coronary artery disease. Methods: Twenty-seven patients underwent 99 Tc m -tetrofosmin SPECT, twenty-six patients underwent 99 Tc m -MIBI SPECT; coronary angiography was performed on patients included in both groups (≥50% luminal diameter stenosis was considered significant coronary stenosis). Results: 99 Tc m -tetrofosmin produced high quality myocardial images from 30 min to several hours postinjection, the outlines of myocardial perfusion images provided by 99 Tc m -tetrofosmin imaging were clearly discernible. One-day exercise/rest 99 Tc m -tetrofosmin myocardial perfusion imaging was feasible and had a high sensitivity for detection of coronary artery disease. Sensitivities of 99 Tc m -tetrofosmin SPECT and 99 Tc m -MIBI SPECT for detecting coronary artery disease were 90% and 94%, respectively. The 95% confidence limits of both sensitivities were 68.65% - 98.77% and 72.33% - 99.86%, respectively; the positive predictive values of both imaging agents were 90.0% and 89.5%, respectively, the 95% confidence limits of those were 68.38% - 98.77% and 72.33% - 99.86% respectively; the positive predictive values of both imaging agents were 90.0% and 89.5%, respectively, the 95% confidence limits of those were 68.38% - 98.77% and 66.38% - 98.70%, respectively; efficiencies of both imaging agents were 85.2% and 88.5%, respectively. The 95% confidence limits of both efficiencies were 65.81% - 95.78% and 69.44 - 98.70%, respectively. The specificity for both imaging agents was 71% and 75%. There was no significant difference among above results (P > 0.05). No ECG abnormalities were found following the injection of 99 Tc m -tetrofosmin SPECT. There were no drug-related effects on blood pressure, heart rate and body temperature. This experiment failed to provide the negative predictive value of the myocardial perfusion imaging with 99 Tc m -tetrofosmin because that few patients with

Reduction of 99mTc-sestamibi and 99mTc-tetrofosmin uptake in MRP-expressing breast cancer cells under hypoxic conditions is independent of MRP function

International Nuclear Information System (INIS)

Kinuya, Seigo; Li, Xiao-Feng; Yokoyama, Kunihiko; Michigishi, Takatoshi; Tonami, Norihisa; Mori, Hirofumi; Shiba, Kazuhiro; Watanabe, Naoto; Shuke, Noriyuki; Bunko, Hisashi

2003-01-01

Hypoxia reduces the uptake of technetium-99m sestamibi (MIBI) in human cancer cell lines. In the current investigation, we attempted to identify the relationship between hypoxia-induced alteration of 99m Tc-MIBI accumulation and expression of multi-drug resistance-associated protein (MRP) in the MCF7/WT breast cancer cell line and its subclonal cell line, MCF7/VP, which expresses high levels of MRP1. A second cationic compound, 99m Tc-tetrofosmin (TF), was also examined. Cellular uptake of 99m Tc-MIBI and 99m Tc-TF was significantly higher in parental MCF7/WT cells than in MCF7/VP cells. Hypoxic conditions generated with a mixture of 95% N 2 and 5% CO 2 reduced cellular uptake of the two tracers in both parental MCF7/WT cells and MRP1-expressing MCF7/VP cells. Cell binding assay with iodine-125-labelled anti-MRP1 antibody demonstrated its specific binding to MCF7/VP cells. Hypoxia did not affect the amount of antibody bound to MCF7/VP cells. These results indicate that hypoxia-induced reduction of tracer uptake in tumour cells is a phenomenon independent of MRP function. (orig.)

Synthesis and characterization of zirconium molybdates of 99 Mo/99m Tc generators

International Nuclear Information System (INIS)

Contreras R, A.; Monroy G, F.; Diaz A, L.V.

2002-01-01

The zirconium molybdates are gels which are used as cation exchangers in the production of 99 Mo/ 99m Tc generators. The synthesis method and the characterization of these gels by thermogravimetry, infrared spectroscopy and X-ray diffraction is presented with the purpose of finding which the factors are that influence in the efficiency of the 99m Tc production. The results show that the quantity of molecular water contained in gel, is possibly the cause of variations of the efficiencies of the 99 Mo/ 99m Tc generator. (Author)

Expression of cytoskeletal and matrix genes following exposure to ionizing radiation: Dose-rate effects and protein synthesis requirements

International Nuclear Information System (INIS)

Woloschak, G.E.; Felcher, P.; Chang-Liu, Chin-Mei

1992-01-01

Experiments were designed to examine the effects of radiation dose-rate and of the protein synthesis inhibitor cycloheximide on expression of cytoskeletal elements (γ- and β-actin and α-tubulin) and matrix elements (fibronectin) in Syrian hamster embryo cells. Past work from our laboratory had already demonstrated optimum time points and doses for examination of radiation effects on accumulation of specific transcripts. Our results here demonstrated little effect of dose-rate for JANUS fission spectrum neutrons when comparing expression of either α-tubulin or fibronectin genes. Past work had already documented similar results for expression of actin transcripts. Effects of cycloheximide, however, revealed several interesting and novel findings: (1) Cycloheximide repressed accumulation of α-tubulin following exposure to high dose-rate neutrons or γ rays; this did not occur following similar low dose-rate exposure (2) Cycloheximide did not affect accumulation of mRNA for actin genes. Cycloheximide abrogated the moderate induction of fibronectin-mRNA which occurred following exposure to γ rays and high dose-rate neutrons. These results suggest a role for labile proteins in the maintenance of α-tubulin and fibronectin mRNA accumulation following exposure to ionizing radiation. In addition, they suggest that the cellular/molecular response to low dose-rate neutrons may be different from the response to high dose-rate neutrons

Synthesis and characterization of zirconium molybdates of {sup 99} Mo/{sup 99m} Tc generators; Sintesis y caracterizacion de molibdatos de zirconio de generadores {sup 99} Mo/{sup 99m} Tc

Energy Technology Data Exchange (ETDEWEB)

Contreras R, A.; Monroy G, F.; Diaz A, L.V. [Instituto Nacional de Investigaciones Nucleares, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

2002-07-01

The zirconium molybdates are gels which are used as cation exchangers in the production of {sup 99} Mo/{sup 99m} Tc generators. The synthesis method and the characterization of these gels by thermogravimetry, infrared spectroscopy and X-ray diffraction is presented with the purpose of finding which the factors are that influence in the efficiency of the {sup 99m} Tc production. The results show that the quantity of molecular water contained in gel, is possibly the cause of variations of the efficiencies of the {sup 99} Mo/{sup 99m} Tc generator. (Author)

Effects of polybrominated diphenyl ethers (PBDEs) and their derivatives on protein disulfide isomerase activity and growth hormone release of GH3 cells.

Science.gov (United States)

Hashimoto, Shoko; Yoshimura, Hiromi; Okada, Kazushi; Uramaru, Naoto; Sugihara, Kazumi; Kitamura, Shigeyuki; Imaoka, Susumu

2012-03-19

Polybrominated diphenyl ethers (PBDEs) have been used in a variety of consumer products such as flame retardants and recently have been known to be widespread environmental pollutants, which probably affect biological functions of mammalian cells. However, the risk posed by PBDE metabolites has not been clarified. Our previous study suggested that bisphenol A (BPA), an endocrine-disrupting chemical, binds to protein disulfide isomerase (PDI) and inhibits its activity. PDI is an isomerase enzyme in the endoplasmic reticulum and facilitates the formation or cleavage of disulfide bonds. PDI consists of a, b, b', and a' domains and the c region, with the a and a' domains having isomerase active sites. In the present study, we tested the effects of 10 kinds of PBDE compounds and their metabolites on PDI. OH-PBDEs specifically inhibited the isomerase activity of PDI, with 4'-OH-PBDE more effective than 2' (or 2)-OH-PBDEs. 4'-OH-PBDE inhibited the isomerase activity of the b'a'c fragment but not that of ab and a'c, suggesting that the b' domain of PDI is essential for the inhibition by 4'-OH-PBDE. We also investigated the effects of these chemicals on the production of growth hormone (GH) in GH3 cells. In GH3 cells, levels of mRNA and protein of GH stimulated by T(3) were reduced by 4'-OH-PBDE and 4'-MeO-PBDE. The reduction in GH expression caused by these compounds was not changed by the overexpression or knockdown of PDI in GH3 cells, while these manipulations of PDI levels significantly suppressed the expression of GH. These results suggest that the biological effects of PBDEs differed depending on their brominated and hydroxylated positions. © 2011 American Chemical Society

Evaluation of the absorbed dose to the kidneys due to Tc99m (DTPA) / Tc99m (Mag3) and Tc99m (Dmsa)

International Nuclear Information System (INIS)

Vasquez A, M.; Murillo C, F.; Castillo D, C.; Rocha J, J.; Sifuentes D, Y.; Sanchez S, P.; Idrogo C, J.; Marquez P, F.

2015-10-01

The absorbed dose in the kidneys of adult patients has been assessed using the biokinetics of radiopharmaceuticals containing Tc 99m (DTPA) / Tc 99m (Mag3) or Tc 99m (Dmsa).The absorbed dose was calculated using the formalism MIRD and the Cristy-Eckerman representation for the kidneys. The absorbed dose to the kidneys due to Tc 99m (DTPA) / Tc 99m (Mag3), are given by 0.00466 mGy.MBq -1 / 0.00339 mGy.MBq -1 . Approximately 21.2% of the absorbed dose is due to the bladder (content) and the remaining tissue, included in biokinetics of Tc 99m (DTPA) / Tc 99m (Mag3). The absorbed dose to the kidneys due to Tc 99m (Dmsa) is 0.17881 mGy.MBq -1 . Here, 1.7% of the absorbed dose is due to the bladder, spleen, liver and the remaining tissue, included in biokinetics of Tc 99m (Dmsa). (Author)

Validation of alternative methods of preparing 99mTc-MAG3

International Nuclear Information System (INIS)

Seetharaman, Shankar; Sosabowski, Michael H.; Ballinger, James R.

2007-01-01

Parameters in the preparation of 99m Tc-mertiatide ( 99m Tc-MAG3) were investigated to determine the importance of total activity, activity concentration, boiling time, and delay before boiling for the radiochemical purity (RCP) and stability of the product. Satisfactory RCP results (>90%) were obtained over a range of concentrations including a dilute preparation for paediatric use. RCP was not affected by the time between the addition of pertechnetate and boiling, but low RCP (<60%) resulted when the kit was boiled for less than 10 min

Tc-99m DMSA renal uptake: influence of biochemical and physiologic factors

International Nuclear Information System (INIS)

Yee, C.A.; Lee, H.B.; Blaufox, M.D.

1981-01-01

Thirty-eight female Sprague-Dawley rats were studied to determine the effects of (a) tubular blockade and (b) commonly encountered changes in hydration and acid-base balance, on the urinary excretion and renal localization of Tc-99m dimercaptosuccinic acid (DMSA). Ten additional rats were studied to quantitate the in vivo protein binding of Tc-99m DMSA, and a final group of 12 animals was used to quantitate DMSA distribution in animals with diminished functional renal mass. Both osmotic diuresis and dehydration by water deprivation for 24 hr resulted in a plasma clearance of DMSA slower than in control animals. Acid-base imbalances significantly affected the renal accumulation of DMSA, and acidosis was associated with markedly increased background due to increased liver accumulation. The protein-bound portion of Tc-99m DMSA in the plasma was high, reaching 89% within the first 5 min, and rising very slightly (n.s.) with time. The unbound portion of DMSA had a plasma clearance slightly higher than the GFR. Ablation of large amounts of renal tissue, resulting in significant decreases in GFR, did not significantly affect the renal localization of DMSA in the intact portions of the kidneys. These data demonstrate that commonly encountered changes in acid-base balance and hydration will significantly alter the biologic distribution of Tc-99m DMSA. These factors should be controlled when carrying out clinical studies

Separation of sup(99m)Tc from 99Mo through a hydrous zirconium oxide column

International Nuclear Information System (INIS)

Mengatti, J.

1980-01-01

The preparation of 99 Mo-,sup(99m)Tc generator based on the adsorption of 99 Mo on hydrous zirconium oxide column, employing the in exchange technique, is described. The adsorption of 99 Mo on hydrous zirconium oxide (HZO) and the separation of sup(99m)Tc, generated by the decay of 99 Mo with saline solution, are analised. The sup(99m)Tc separation yield, pH of the eluted solution, aspect of the elution curve and the adsorption of 99 Mo on hydrous zirconium oxide calcined at 800 0 C are studied. The chemical and radioactive purities of the final product are analysed and the variation of the elution yield for successive elutions is studied. (Author) [pt

Studies of techniques for the post-elution concentration of 99mTc obtained from gel type 99Mo/99mTc generators

International Nuclear Information System (INIS)

Suzuki, Katia Noriko

2009-01-01

On average 80% of the radiopharmaceuticals used in Nuclear Medicine are labeled with 99 mTc due to its physical properties and easy attainment through of 99 Mo/ 99 mTc generators. The Directory of Radiopharmacy (DIRF) of IPEN-CNEN/SP developed a gel type chromatographic generator of MoZr with 99 Mo produced by 98 Mo(n,γ) 99 Mo reaction that occurs at the IEA-R1 Nuclear Reactor. The gel is composed of zirconium molybdate with elution volume of 12 mL with an activity of 11100 MBq (300 mCi) producing a radioactive concentration of 925 MBq (25 mCi)/mL. The fission generator gives a higher radioactive concentration around 1850 MBq (50 mCi)/mL. The aim of this work is to study a system of post-elution concentration of 99 mTc for the attainment of a high enough radioactive concentration to meet the demands of the market, with a proved quality. Two types of systems of post-elution concentration were developed: the single and the tandem. The most appropriate system for the gel generator of 99 Mo/ 99 mTc, being at the same time sterile and vacuum automated, was the tandem system using Dionex 2.5 cc/QMA cartridges. The gel generator is eluted with 10 mL of solution of 0.1% NaCl and the pertechnetate anion is retained in the QMA cartridge and further eluted with 4 mL of saline. The process takes no more than 30 minutes. The elution efficiency of the system of concentration was 90 %. At the beginning of 2009 a global crisis in the supply of 99 Mo took place making it necessary the development of alternative technologies for the production of 99 Mo/ 99 mTc generators using fission produced 99 Mo and the development of an appropriate method to extend the useful life of this generator. The results of this study showed that the same system developed for the post- concentration of the gel generator can be employed for the fission generator, using the tandem system, giving a concentration factor of 3 for the elution of 99 mTc. (author)

Synthetic polymeric substrates as potent pro-oxidant versus anti-oxidant regulators of cytoskeletal remodeling and cell apoptosis.

Science.gov (United States)

Sung, Hak-Joon; Chandra, Prafulla; Treiser, Matthew D; Liu, Er; Iovine, Carmine P; Moghe, Prabhas V; Kohn, Joachim

2009-03-01

The role of reactive oxygen species (ROS)-mediated cell signal transduction pathways emanating from engineered cell substrates remains unclear. To elucidate the role, polymers derived from the amino acid L-tyrosine were used as synthetic matrix substrates. Variations in their chemical properties were created by co-polymerizing hydrophobic L-tyrosine derivatives with uncharged hydrophilic poly(ethylene glycol) (PEG, Mw = 1,000 Da), and negatively charged desaminotyrosyl-tyrosine (DT). These substrates were characterized for their intrinsic ability to generate ROS, as well as their ability to elicit Saos-2 cell responses in terms of intracellular ROS production, actin remodeling, and apoptosis. PEG-containing substrates induced both exogenous and intracellular ROS production, whereas the charged substrates reduced production of both types, indicating a coupling of exogenous ROS generation and intracellular ROS production. Furthermore, PEG-mediated ROS induction caused nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase and an increase in caspase-3 activity, confirming a link with apoptosis. PEG-rich pro-oxidant substrates caused cytoskeletal actin remodeling through beta-actin cleavage by caspase-3 into fractins. The fractins co-localized to the mitochondria and reduced the mitochondrial membrane potential. The remnant cytosolic beta-actin was polymerized and condensed, events consistent with apoptotic cell shrinkage. The cytoskeletal remodeling was integral to the further augmentation of intracellular ROS production. Conversely, the anti-oxidant DT-containing charged substrates suppressed the entire cascade of apoptotic progression. We demonstrate that ROS activity serves an important role in "outside-in" signaling for cells grown on substrates: the ROS activity couples exogenous stress, driven by substrate composition, to changes in intracellular signaling. This signaling causes cell apoptosis, which is mediated by actin remodeling.

The preparation of {sup 99m}Tc from {sup 99}Mo-{sup 99m}Tc using Poly-Zirconium Compound (PZC)

Energy Technology Data Exchange (ETDEWEB)

Laohawilai, S [Isotope Production Div., Office of Atomic Energy for Peace (Thailand)

1998-10-01

The process of for providing the {sup 99m}Tc-gel generator followed the protocol that received from Department of Radioisotopes, Tokai Research Establishment, JAERI. Sodium molybdate (molybdenum-99), pH 7 with concentration 20 mg/ml and activity nearly 1 mCi/ml was added into the adsorbent (PZC). The total activity of {sup 99}Mo was about 10 mCi and the heating time was varied from 3-18 hours at 70degC. The properties of the gel were studied for elution profile and elution efficiency. The molybdenum breakthrough in sodium pertechnetate (technetium-99m) was also performed. (author)

Neoplastic progression of the human breast cancer cell line G3S1 is associated with elevation of cytoskeletal dynamics and upregulation of MT1-MMP

Czech Academy of Sciences Publication Activity Database

Tolde, O.; Rosel, D.; Mierke, C.T.; Paňková, D.; Folk, P.; Veselý, Pavel; Brabek, J.

2010-01-01

Roč. 36, č. 4 (2010), s. 833-839 ISSN 1019-6439 R&D Projects: GA MŠk(CZ) LC06061 Institutional research plan: CEZ:AV0Z50520514 Keywords : invasiveness * neoplastic progression * cytoskeletal dynamics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.571, year: 2010

Experimental substantiation of myocardial affection visualization by means of pyrophosphate-sup(99m)Tc

Energy Technology Data Exchange (ETDEWEB)

Shepeleva, I I; Saprygin, D B; Saks, V A; Kramer, A A; Kashtelyan, L S [Akademiya Meditsinskikh Nauk SSSR, Moscow. Vsesoyuznyj Kardiologicheskij Nauchnyj Tsentr; Akademiya Meditsinskikh Nauk SSSR, Moscow. Inst. Serdechno-Sosudistoj Khirurgii)

1979-03-01

To study the mechanisms of accumulation of the pyrophosphate-sup(99m)TcSn complex a model of an isolated rat heart perfused according to Langendorf under conditions was used. The results of the experiment showed that intensive accumulation of the radionuclide in the myocardium began already at the first minutes of anoxia, i.e. at the stage of reversible changes when reoxygenation brought about a drop in the level of accumulated radioactivity down to the normal limit. Anoxia lasting for 5 minutes led to a 10 per cent accumulation of the entire dose of radioactivity in the myocardium, that lasting for 10 minutes-up to 18 per cent. As a result of a 5-minute reoxygenation after a 10-minute anoxia the level of accumulated radioactivity fell down to 4-5 per cent. Reoxygenation after s 20-30-minute anoxia produced no effect on the curve of the radionuclide accumulation in the heart. Alongside radiometric studies the content of macroergs (ATP and creatine phosphate) in the norm and in development of anoxia was determined. The accumulation of the pyrophosphate-sup(99m)TcSn complex in the myocardial cells is closely connected with energy metabolism of the cell and, is apparently, caused by changes in the cell membrane permeability by this complex.

A comparative study of 99Tcm-MDP, 99Tcm(V)-DMSA and 99Tcm-Citrate in diagnosis of bone malignant tumors and bone/joint infections

International Nuclear Information System (INIS)

Wu Zhaozhong; Wu Boyi; Lin Wei; Wei Xueli; Wu Hengfu; Fan Ziwen; Ouyang Zhi; Wu Changwei; Yuan Gewen

2003-01-01

The purpose of this study was to assess the diagnostic value of scans with 99 Tc m (V)-dimercaptosuccinic acid (DMSA) to localize bone metastases and to evaluate the capability to diagnose bone/joint infections with scans using 99 Tc m -Citrate. Eighteen patients referred to bone metastases and eighteen patients referred to bone and joint infection were studied. In all patients, a bone scan of 99 Tc m -MDP was obtained initially. Subsequently, comparative scans with 99 Tc m (V)-DMSA and 99 Tc m -Citrate were conducted successively. Pathologic finding and/or microbiological finding, X-ray CT and/or MRI, and/or clinical follow-up (until symptoms disappeared) were considered to be proof of the presence of bone metastases and bone/joint infection. All of the eighteen patients with diagnosed bone metastases and of the eighteen patients with diagnosed bone and joint infection had positive 99 Tc m -MDP scintigraphy. The fifteen patients with diagnosed bone metastases and the fifteen patients with diagnosed bone/joint infection had increased 99 Tc m (V) -DMSA accumulation at certain areas matched with those shown in 99 Tc m -MDP scans, and only one patient with diagnosed bone metastases and the fifteen patients with diagnosed bone and joint infection had increased 99 Tc m -Citrate accumulation at certain areas matched with those shown in 99 Tc m -MDP scans. 99 Tc m -MDP scans show 64 bone lesions in the bone metastases while 49 lesions by the 99 Tc m (V)-DMSA scans and only one lesion by the 99 Tc m -Citrate scans respectively. And 99 Tc m -MDP scans show 22 bone lesions in the bone and joint infection while 17 lesions by the 99 Tc m (V)-DMSA imaging and 16 lesions by the 99 Tc m -Citrate imaging respectively. For bone metastases diagnosis, the sensitivity of 99 Tc m (V)-DMSA imaging and 99 Tc m -Citrate imaging were 76.56% and 1.56%, respectively, and the specificity were only 22.73% and 27.27%, respectively. For bone and joint infection diagnosis, the sensitivity of two

Generator of 99m Tc with MnO2 as support of 99 Mo

International Nuclear Information System (INIS)

Granados C, F.; Serrano G, J.

2002-01-01

The generator of 99m Tc with MnO 2 as support of 99 Mo was studied. By mean of static experiments the retention of 99 Mo in MnO 2 in function of the stirring time and of the p H value of the solution of 99 Mo. It was found that the 99 Mo presents 100% of retention in MnO 2 in the rank of p H 3-11 and the balance was reached before of 10 minutes. In dynamic conditions the retention of 99 Mo in MnO 2 at p H=5 was also higher: 99.72%. The generated 99m Tc can be separated from 99 Mo, adsorbed in MnO 2 packed in the column, using distilled water at p H=5 or NaCl solution at 0.9%. With saline solution the elution yields were greater than 80% and only an aliquot of 5 ml was necessary for obtaining this yield. The better results were obtained when the column was packed with 1 g of MnO 2 . The water and the saline solution were passed through of the column with a flux of 1.25 ml/min. (Author)

JENDL dosimetry file 99 (JENDL/D-99)

International Nuclear Information System (INIS)

Kobayashi, Katsuhei; Iwasaki, Shin

2002-01-01

The JENDL Dosimetry File 99 (JENDL/D-99), which is a revised version of the JENDL Dosimetry File 91 (JENDL/D-91), has been compiled and released for the determination of neutron flux and energy spectra. This work was undertaken to remove the inconsistency between the cross sections and their covariances in JENDL/D-91 since the covariances were mainly taken from IRDF-85 although the cross sections were based on JENDL-3. Dosimetry cross sections have been evaluated for 67 reactions on 47 nuclides together with covariances. The cross sections for 34 major reactions and their covariances were simultaneously generated, and the remaining 33 reaction data were mainly taken from JENDL/D-91. Latest measurements were taken into account in the evaluation. The resultant evaluated data are given in the neutron energy region below 20 MeV in both of point-wise and group-wise files in the ENDF-6 format. In order to confirm the reliability of the evaluated data, several integral tests have been carried out: comparisons with average cross sections measured in fission neutron fields, fast/thermal reactor spectra, DT neutron fields and Li(d,n) neutron fields. It was found from the comparisons that the cross sections calculated from JENDL/D-99 are generally in good agreement with the measured data. The contents of JENDL/D-99 and the results of the integral tests are described in this report. All of the dosimetry cross sections are shown in a graphical form in the Appendix. (author)

Kinetics and Pathways for the Debromination of Polybrominated Diphenyl Ethers by Bimetallic and Nanoscale Zerovalent Iron: Effects of Particle Properties and Catalyst

Science.gov (United States)

Zhuang, Yuan; Jin, Luting; Luthy, Richard G.

2012-01-01

Polybrominated diphenyl ethers (PBDEs) are recognized as a new class of widely-distributed and persistent contaminants for which effective treatment and remediation technologies are needed. In this study, two kinds of commercially available nanoscale Fe° slurries (Nanofer N25 and N25S), a freeze-dried laboratory-synthesized Fe° nanoparticle (nZVI), and their palladized forms were used to investigate the effect of particle properties and catalyst on PBDE debromination kinetics and pathways. Nanofers and their palladized forms were found to debrominate PBDEs effectively. The laboratory-synthesized Fe° nanoparticles also debrominated PBDEs, but were slower due to deactivation by the freeze-drying and stabilization processes in the laboratory synthesis. An organic modifier, polyacrylic acid (PAA), bound on N25S slowed PBDE debromination by a factor of three to four compared to N25. The activity of palladized nZVI (nZVI/Pd) was optimized at 0.3 Pd/Fe wt% in our system. N25 could debrominate selected environmentally-abundant PBDEs, including BDE 209, 183, 153, 99, and 47, to end products di-BDEs, mono-BDEs and diphenyl ether (DE) in one week, while nZVI/Pd (0.3 Pd/Fe wt%) mainly resulted in DE as a final product. Step-wise major PBDE debromination pathways by unamended and palladized Fe° are described and compared. Surface precursor complex formation is an important limiting factor for palladized Fe° reduction as demonstrated by PBDE pathways where steric hindrance and rapid sequential debromination of adjacent bromines play an important role. PMID:22732301

Availability of {sup 99}Tc in undisturbed soil cores

Energy Technology Data Exchange (ETDEWEB)

Denys, Sebastien; Echevarria, Guillaume E-mail: guillaume.echevarria@ensaia.inpl-nancy.fr; Florentin, Louis; Leclerc-Cessac, Elisabeth; Morel, Jean-Louis

2003-07-01

Models for safety assessment of radioactive waste repositories need accurate values of the soil-to-plant transfer of radionuclides. In oxidizing environments, {sup 99}Tc is expected to occur as pertechnetate ({sup 99}TcO{sub 4}{sup -}). Due to its high mobility, leaching of this element in the field might be important, potentially affecting the reliability of estimated transfer parameters of {sup 99}Tc as measured in closed experimental systems such as hydroponics or pot experiments. The aim of this experiment was to measure the leaching of {sup 99}Tc in undisturbed irrigated soil cores under cultivation as well as plant uptake and to study the possible competition between the two transfer pathways. Undisturbed soil cores (50x50 cm) were sampled from a Rendzic Leptosol (R), a colluvial Fluvic Cambisol (F) and a Dystric Cambisol (D) using PVC tubes (three cores sampled per soil type). Each core was equipped with a leachate collector at the bottom, allowing the monitoring of {sup 99}Tc leaching through the cores. Cores were placed in a greenhouse and maize (Zea mays L., cv. DEA, Pioneer[reg]) was sown. After 135 d, maize was harvested and radioactivity determined in both plant and water samples. Results showed that during the growing period, leaching of {sup 99}Tc was limited, due to the high evapotranspiration rate of maize. After harvest, leaching of {sup 99}Tc went on because of the absence of evapotranspiration. Effective uptake (EU) of {sup 99}Tc in leaves and grains was calculated. EU reached 70% of the input in the leaves and was not significantly different among soils. These results confirmed those obtained from pot experiments, even though leaching was allowed to occur in close-to-reality hydraulical conditions. As a consequence, it was concluded that pot experiments are an adequate surrogate for more complex 'close-to-reality' experimental systems for measuring transfer factors.

Status of {sup 99}Mo-{sup 99m}Tc production development by (n, {gamma}) reaction

Energy Technology Data Exchange (ETDEWEB)

Tsuchiya, Kunihiko; Kaminaga, Masanori; Ishihara, Masahiro; Kawamura, Hiroshi [Japan Atomic Energy Agency, Oarai Research and Development Center, Oarai, Ibaraki (Japan); Mutalib, Abdul [National Nuclear Energy Agency of Indonesia (BATAN), Tangerang (Indonesia); Chakrov, Petr [Institute of Nuclear Physics, National Nuclear Center of Republic of Kazakhstan (INP-NNC-RK), Almaty (Kazakhstan)

2012-03-15

Technetium-99m ({sup 99m}Tc) is one of the most commonly used radioisotopes in the field of nuclear medicine. As one of effective uses of the JMTR, JAEA has a plan to produce {sup 99}Mo by (n, {gamma}) method, a parent nuclide of {sup 99m}Tc. JAEA has performed R and D on production method of {sup 99}Mo-{sup 99m}Tc in JMTR cooperating with foreign organizations and relevant Japanese enterprises under the cooperation programs. In this paper, present status of R and D for production of {sup 99}Mo-{sup 99m}Tc in JMTR under international cooperation is introduced and constructions of the irradiation and PIE facilities at the JMTR site are also described. (author)

99mTc-EDTA and 99mTc-DTPA complexes as hydrological tracers

International Nuclear Information System (INIS)

Dominguez, J.; Borroto, J.; Nazco, J.; Perez, E.; Gamboa, R.; Cruz, J.

2002-01-01

The [ 99m Tc-DTPA] 2- and [ 99m Tc-EDTA] 1- were evaluated as radiotracers for short time hydrological studies. Their complex stability after labelling with 9.25 GBq of 99m Tc, the behaviour against pH variations, from 5 to 9, in simulated solutions and in natural river waters and the sorption of these compounds on the river sediments, were tested in laboratory experiments. Finally field double tracing experiments were carried out for each of labelling complexes and Rhodamine WT. From recovery calculations not losses of the 99m Tc activity were observed. The shape of the RTD curves of the [ 99m Tc-DTPA] 2- and [ 99m Tc-EDTA] 1 were quite similar to the Rhodamine Wt ones. May be concluded that both complexes behaved conservatively on the studied environmental conditions. (author)

Optimization of the 99m Tc generator with hydrotalcite as support of 99 Mo

International Nuclear Information System (INIS)

Aranda O, N.

2004-01-01

In the last years, in the laboratories of the National Institute of Nuclear Investigations (ININ) its have been investigating to the hydrotalcite like a material of support of the 99 Mo with the purpose of developing a new technetium generator. During the development of the investigations it has been demonstrated that when putting in contact to the HTC with an aqueous solution that contains anions of any type, the HTC re hydrate and the structure is regenerated to laminate of the hydrotalcite. If the present anions in the solution are molybdate anions (MoO 4 2- ), these anions passed to be part of the structure of the hydrotalcite (HT-MoO 4 ). These anions can contain, in turn, 99 Mo in their composition ( 99 MoO 4 2- ) and equally they can pass to be part of the structure of the hydrotalcite forming the HT- 99 MoO 4 . When the HT- 99 MoO 4 is packed in a column, the 99m Tc that it takes place when decaying the 99 Mo radioactively can separate the column using aqueous solution of NaCl. This way, in previous studies (Serrano, 2000) it was found that the aqueous solution of NaCl to 0.5% it is the but appropriate for elutriate at the 99m Tc from the column the yield of the elution of the 99m Tc was since high (98%) in the first elution, and the radionuclide contamination caused by the presence of 99 Mo in the eluate it was low ( 4 2- for gram of HTC). These facts, standing out the high capacity of the HTC to retain molybdate ions, they drove from a direct way to investigate the optimization of the generator of 99m Tc, with hydrotalcite like support of the 99 Mo, using 99 Mo of low specific activity. This finishes radioactive material it can be obtained by the irradiation of the 98 Mo (in the chemical form of MoO 3 or (NH 4 ) 2 MoO 4 ), with a flow of thermal neutrons in the nuclear reactor TRIGA Mark lll that one has in the Nuclear Center N abor Carrillo Flores . The technetium generators with alumina like support of the 99 Mo use 99 Mo of high specific activity

Evaluation of 99Mo/99mTc generator experiment using PZC material and irradiated natural molybdenum

International Nuclear Information System (INIS)

Khongpetch, P.; Chingjit, S.; Dangprasert, M.; Rangsawai, W.; Virawat, N.

2006-01-01

Technetium-99m ( 99m Tc) is the most widely used radioisotope in nuclear medicine, accounting for more than 80% of all diagnostic nuclear medicine procedure. 99m Tc is almost exclusively produced from the decay of its parent molybdenum-99 ( 99 Mo). The present sources of 99 Mo are research reactors by using the (n, γ) nuclear reaction with natural molybdenum, resulting in inexpensive but low specific activity 99 Mo, or by neutron-induced fission of uranium-235, which result in expensive but high specific activity 99 Mo. The technology requirement for processing of 99 Mo from the (n, γ) 'activation method' is rather simple, and is within the reach of most developing countries operating research reactors. In the fission method' the technological and infrastructure requirements are some complex, and possibly can be sustained only by countries with advanced nuclear technology. To overcome these difficulties, Japan Atomic Energy Research Institute (JAERI) and KAKEN company have developed alternative technology for 99 Mo/ 99m Tc generator by using a molybdenum absorbent called Poly Zirconium compound (PZC) and irradiated natural molybdenum. The paper describes experiments for evaluation the performance of PZC as a column packing material for 99 Mo/ 99m Tc generator from (n, γ) 99 Mo. (author)

Tc-99 Adsorption on Selected Activated Carbons - Batch Testing Results

Energy Technology Data Exchange (ETDEWEB)

Mattigod, Shas V.; Wellman, Dawn M.; Golovich, Elizabeth C.; Cordova, Elsa A.; Smith, Ronald M.

2010-12-01

conducted to ascertain the effects of changing pH showed that at pH values of 6.5 and 7.5, no significant differences existed in Tc-adsorption performance for three of the carbons, but the fourth carbon performed better at pH 7.5. When the pH was increased to 8.5, a slight decline in performance was observed for all carbons. Tests conducted to ascertain the temperature effect on Tc-99 adsorption indicated that at 21 ºC, 27 ºC, and 32 ºC there were no significant differences in Tc-99 adsorption for three of the carbons. The fourth carbon showed a noticeable decline in Tc-99 adsorption performance with increasing temperature. The presence of volatile organic compounds (VOCs) in the source water did not significantly affect Tc-99 adsorption on either of two carbons tested. Technetium-99 adsorption differed by less than 15% with or without VOCs present in the test water, indicating that Tc-99 adsorption would not be significantly affected if VOCs were removed from the water prior to contact with carbon.

Preliminary studies of 99mTc-PQQ-NMDAR binding and effect of specificity binding by mannitol

International Nuclear Information System (INIS)

Xingqin Zhou; Yanyan Kong; Guoxian Cao; Jiankang Zhang

2013-01-01

Pyrroloquinoline quinone (PQQ) is a powerful neuroprotectant that specifically binds to brain NMDA receptors and inhibits excitotoxicity. Imaging this binding reaction in the brain remains a long sought goal in this field of study, and one of the primary challenges remaining is enabling soluble labeled PQQ to pass the blood-brain barrier (BBB). Previously, our group successfully labeled PQQ with Technetium-99m ( 99m Tc), a metastable nuclear isomer used in radioactive isotope medical tests. In this work, we determined the specific binding of 99m Tc-PQQ and NMDAR by radioligand receptor assay. Ebselen (EB) and MK-801 both effectively inhibited 99m Tc-PQQ binding. We then investigated methods of opening the BBB using mannitol to enable entry to the brain by 99m Tc-PQQ. Our results showed that 7.5 mL/kg of 20 % mannitol effectively opened the BBB and 20 min was the optimum treatment time. Competition studies showed that mannitol did not affect the specific binding between 99m Tc-PQQ and NMDA receptors. Using this method, the amount of 99m Tc-PQQ uptake and retention was increased most significantly in the hippocampus and cortex, and re-opening the BBB did not affect binding. Together, our results demonstrate that the use of mannitol to open the BBB may contribute significantly to improving image quality by increasing the uptake amount of a water-soluble agent in brain. (author)

Determination of Tc-99 in radioactive wastes; Determinacion de Tc-99 en desechos radiactivos

Energy Technology Data Exchange (ETDEWEB)

Rivera S, A. A.

2015-07-01

Tc-99 is a fission product and one of the most important radionuclides from the view point of safety assessment for the disposal of radioactive waste because of its long half-life (2.1 x 10{sup 5} years) and high mobility in soil-water systems, if this is released into the environment in significant quantities can concentrate on plants and animals. Tc-99 is a pure beta emitter with a maximum energy of 292 KeV, so their quantification imposes destructive methods to be analyzed by liquid scintillation. Therefore the quantification of Tc-99 in ion exchange resins requires of the mineralization of these and separation of Tc-99 of other radioisotopes present in the resin. Therefore the object of this thesis is to develop a quantification method of Tc-99 content in spent exchange resins. So in order to track the behavior of technetium during digestion exchange resins and radiochemical separation, given its high volatility, in this work the {sup 99m}Tc is used. To determine the degree of mineralization of the resins, an analysis was performed by chromatography. Subsequently the method used to determine the percentage of {sup 99m}Tc aerosolized during mineralization of resin is described. After the method for the radiochemical separation of {sup 99m}Tc is presented by liquid-liquid extraction using crown ether as extractant; for this testing was performed by varying the molarity of the extractant, the ratio of solvent extractant, type of digestion of the resin and the presence of Sr-85, in order to study the behavior of {sup 99m}Tc in the presence of this radioisotope. Finally, a track beta spectra of a sample of {sup 99m}Tc eluted from a generator {sup 99}Mo/{sup 99m}Tc function of time was performed. (Author)

Scintigraphic findings on 99mTc-MDP, 99mTc-sestamibi and 99mTc-HMPAO images in Gaucher's disease

International Nuclear Information System (INIS)

Mariani, G.; Molea, N.; La Civita, L.; Porciello, G.; Lazzeri, E.; Ferri, C.

1996-01-01

We report here on the use of the lipophilic cationic complex technetium-99m sestamibi ( 99m Tc-MIBI), employed as an indicator of increased cellular density and metabolic activity, to evaluate Gaucher cell infiltrates in the bone marrow; 99m Tc-hexametazime ( 99m Tc-HMPAO) was also employed, as a pure indicator of lipidic infiltration in the bone marrow. A 67-year-old patient with known type 1 Gaucher's disease presented with a painful left hip and knee and difficulty in gait subsequent to traumatic fracture of the left femoral neck that had required implant of a fixation screw-plaque. Bone scan with 99m Tc-methylene diphosphonate revealed reduced uptake at the distal metaphyseal-epiphyseal femoral region. In addition, whole-body maps and spot-view acquisitions of the thighs and legs were recorded at both 30 min and 2.5 h after the injection of 99m Tc-MIBI: the scintigraphic pattern clearly showed increased uptake at several sites involved by Gaucher deposits in the bone marrow (both knees, with variable intensity in different areas), matching the bone changes detected by conventional x-ray. The target to non-target ratios slowly decreased with time, from an average value of 2.25 in the early scan to an average value of 2 in the delayed scan. The lipid-soluble agent 99m Tc-HMPAO exhibited a superimposable scintigraphic pattern of accumulation at the involved sites, though with lower target to non-target ratios (1.27-1.48). The results obtained in this patient suggest a potential role of 99m Tc-MIBI in the scintigraphic evaluation of Gaucher's lipid deposits in the bone marrow. If the results are confirmed in other patients, this radiopharmaceutical would offer clear advantages over 133 Xe because of its wider availability and greater practicality (i.v. administration of 99m Tc-MIBI versus inhalation of 133 Xe, and use of a single gamma camera instead of two as with 133 Xe). (orig.). With 3 figs

Localization diagnosis of hyperfunctional parathyroid gland using 99Tcm-MIBI and 99TcmO4- imaging

International Nuclear Information System (INIS)

Zhang Fenru; Deng Huixing; Duan Xiaoyi; Xue Jianjun; Gao Rui

2010-01-01

Objective: To study the localization diagnosis value of nuclide imaging by 99 Tc m -MIBI double phase parathyroid combined with 99 Tc m O 4 - thyroid imaging in patients with hyperparathyroidism (HPT). Methods: Patients with primary HPT were 36 cases. Control groups were 10 cases with thyroid disease. Early phase imaging was performed in 15 minute after injecting imaging agent 99 Tc m -MIBI. Delay phase imaging was performed in 2 hours. 36 HPT patients and 10 cases control groups were also performed 99 Tc m O 4 - thyroid imaging 24 hours later. The two kinds of imaging were compared with each other, were analyzed, and were underwent imaging subtracted by eyes and imaging results judgment. Results: In 36 cases of HPT patients, 34 cases showed positive result imaging with 99 Tc m -MIBI/ 99 Tc m O 4 - imaging. 2 cases showed false negative result. Positive rate was 94.44 % with 99 Tc m -MIBI/ 99 Tc m O 4 - imaging. The positive result imaging showed abnormal increased uptake of 99 Tc m -MIBI. In 36 cases of HPT patients, 12 cases showed positive result with single 99 Tc m -MIBI imaging. 4 cases showed false negative imaging. 20 cases showed ambiguous positive results. Positive rate was 88.89% (55.56% was ambiguous positive results) with single 99 Tc m -MIBI imaging. In 10 cases control groups, 3 cases showed false positive results with single 99 Tc m -MIBI imaging. 1 case showed ambiguous false positive results. No case showed false positive result with 99 Tc m -MIBI/ 99 Tc m O 4 - imaging. Conclusion: 99 Tc m -MIBI parathyroid double phase imaging combined with 99 Tc m O 4 - thyroid imaging have important value for diagnoses and localization of hyperparathyroidism. 99 Tc m -MIBI/ 99 Tc m O 4 - imaging have higher positive rate and higher specificity than single 99 Tc m -MIBI imaging for diagnoses and localization of hyperfunction parathyroid gland. (authors)

Optimization of the {sup 99m} Tc generator with hydrotalcite as support of {sup 99} Mo; Optimizacion del generador de {sup 99m} Tc con hidrotalcita como soporte del {sup 99} Mo

Energy Technology Data Exchange (ETDEWEB)

Aranda O, N

2004-07-01

In the last years, in the laboratories of the National Institute of Nuclear Investigations (ININ) its have been investigating to the hydrotalcite like a material of support of the {sup 99} Mo with the purpose of developing a new technetium generator. During the development of the investigations it has been demonstrated that when putting in contact to the HTC with an aqueous solution that contains anions of any type, the HTC re hydrate and the structure is regenerated to laminate of the hydrotalcite. If the present anions in the solution are molybdate anions (MoO{sub 4}{sup 2-}), these anions passed to be part of the structure of the hydrotalcite (HT-MoO{sub 4}). These anions can contain, in turn, {sup 99} Mo in their composition ({sup 99}MoO{sub 4}{sup 2-}) and equally they can pass to be part of the structure of the hydrotalcite forming the HT-{sup 99}MoO{sub 4}. When the HT-{sup 99}MoO{sub 4} is packed in a column, the {sup 99m}Tc that it takes place when decaying the {sup 99}Mo radioactively can separate the column using aqueous solution of NaCl. This way, in previous studies (Serrano, 2000) it was found that the aqueous solution of NaCl to 0.5% it is the but appropriate for elutriate at the {sup 99m}Tc from the column the yield of the elution of the {sup 99m}Tc was since high (98%) in the first elution, and the radionuclide contamination caused by the presence of {sup 99}Mo in the eluate it was low (<0.01%). In this investigation it was also found that the HTC has a high capacity to retain molybdate ions (255.1 mg of ions MoO{sub 4}{sup 2-} for gram of HTC). These facts, standing out the high capacity of the HTC to retain molybdate ions, they drove from a direct way to investigate the optimization of the generator of {sup 99m}Tc, with hydrotalcite like support of the {sup 99}Mo, using {sup 99}Mo of low specific activity. This finishes radioactive material it can be obtained by the irradiation of the {sup 98}Mo (in the chemical form of MoO{sub 3} or (NH{sub 4

Uptake, translocation, and debromination of polybrominated diphenyl ethers in maize

Institute of Scientific and Technical Information of China (English)

Moming Zhao; Shuzhen Zhang; Sen Wang; Honglin Huang

2012-01-01

Uptake,translocation and debromination of three polybrominated diphenyl ethers(PBDEs),BDE-28,-47 and-99,in maize were studied in a hydroponic experiment.Roots took up most of the PBDEs in the culture solutions and more highly brominated PBDEs had a stronger uptake capability.PBDEs were detected in the stems and leaves of maize after exposure but rarely detected in the blank control plants.Furthermore,PBDE concentrations decreased from roots to stems and then to leaves,and a very clear decreasing gradient was found in segments upwards along the stem.These altogether provide substantiating evidence for the acropetal translocation of PBDEs in maize.More highly brominated PBDEs were translocated with more difficulty.Radial translocation of PBDEs from nodes to sheath inside maize was also observed.Both acropetal and radial translocations were enhanced at higher transpiration rates,suggesting that PBDE transport was probably driven by the transpiration stream.Debromination of PBDEs occurred in all parts of the maize,and debromination patterns of different parent PBDEs and in different parts of a plant were similar but with some differences.This study for the first time provides direct evidence for the acropetal translocation of PBDEs within plants,elucidates the process of PBDE transport and clarifies the debromination products of PBDEs in maize.

Bioavailability and mass balance studies of a commercial pentabromodiphenyl ether mixture in male Sprague-Dawley rats.

Science.gov (United States)

Huwe, Janice; Hakk, Heldur; Lorentzsen, Margaret

2007-01-01

Polybrominated diphenyl ethers (PBDE) are common flame retardants used in polyurethane foam, high impact polystyrene, and textiles which appear to be increasing in the environment and biota. Two PBDE congeners that are particularly prominent in environmental samples are 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and 2,2',4,4',5-pentabromodiphenyl ether (BDE-99). These two congeners are major components in penta-BDE formulations which constitute a minor percentage of the commercial PBDE market. In order to determine the bioavailability and bioconcentration potential of these PBDEs, we have conducted a feeding experiment in rats, dosing with low amounts of a commercial penta-BDE mixture for 21 days to mimic an environmental exposure. The carcasses, livers, and feces from control and dosed rats were quantitated for PBDEs by a high resolution GC-MS isotope dilution method. Between 25% and 50% of each of the dosed congeners was retained in the rats with the liver being a minor depot (commercial mixture. Conclusions from the study suggest that the tetra- to hexa-BDEs present in commercial penta-BDE formulations are largely bioavailable, that bioavailability in the rat is not dependent on the degree of bromination, and that metabolism may occur to a large extent during a chronic exposure.

Evaluation of the absorbed dose to the kidneys due to Tc{sup 99m} (DTPA) / Tc{sup 99m} (Mag3) and Tc{sup 99m} (Dmsa); Evaluacion de la dosis absorbida en los rinones debido al Tc{sup 99m} (DTPA) / Tc{sup 99m} (MAG3) y Tc{sup 99m} (DMSA)

Energy Technology Data Exchange (ETDEWEB)

Vasquez A, M.; Murillo C, F.; Castillo D, C.; Rocha J, J.; Sifuentes D, Y.; Sanchez S, P. [Universidad Nacional de Trujillo, Av. Juan Pablo II s/n, Trujillo (Peru); Idrogo C, J.; Marquez P, F., E-mail: marvva@hotmail.com [Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos 2520, Lima (Peru)

2015-10-15

The absorbed dose in the kidneys of adult patients has been assessed using the biokinetics of radiopharmaceuticals containing Tc{sup 99m} (DTPA) / Tc{sup 99m} (Mag3) or Tc{sup 99m} (Dmsa).The absorbed dose was calculated using the formalism MIRD and the Cristy-Eckerman representation for the kidneys. The absorbed dose to the kidneys due to Tc{sup 99m} (DTPA) / Tc{sup 99m} (Mag3), are given by 0.00466 mGy.MBq{sup -1} / 0.00339 mGy.MBq{sup -1}. Approximately 21.2% of the absorbed dose is due to the bladder (content) and the remaining tissue, included in biokinetics of Tc{sup 99m} (DTPA) / Tc{sup 99m} (Mag3). The absorbed dose to the kidneys due to Tc{sup 99m} (Dmsa) is 0.17881 mGy.MBq{sup -1}. Here, 1.7% of the absorbed dose is due to the bladder, spleen, liver and the remaining tissue, included in biokinetics of Tc{sup 99m} (Dmsa). (Author)

Study of {sup 99m}Tc-DMSA biodistribution in experimental animals

Energy Technology Data Exchange (ETDEWEB)

Castro, Thais O.M. de; Silva, Natanael G. da; Colturato, Maria T.; Felgueiras, Carlos F.; Mengatti, Jair; Fukumori, Neuza T.O.; Matsuda, Margareth M.N.; Araújo, Elaine B. de, E-mail: thais.castrom@gmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Radiofarmacia

2017-11-01

{sup 99m}Tc-DMSA, succimer ({sup 99m}Tc), is a radiopharmaceutical commonly used in nuclear medicine for renal function evaluation by imaging. In order to achieve adequate labeling of the product with good radiochemical yield and standardized biological distribution, the interval of 185 - 3700 MBq should be kept in a maximum volume of 3 mL for product labeling. Moreover, one should avoid exposing the reconstituted solution to oxygen and using the product after four hours post labeling. The aim of the study was to quantify and evaluate the influence of different DMSA complexes on biological distribution of the radiopharmaceutical in experimental animals, taking in account variations in the labeling parameters. Radiochemical purity was determined by paper and thin layer chromatography using both acetone/Whatman 3MM, 0.9% NaCl/TLC-SG and n-propanol/ H{sub 2}O/acetic acid (4:3:1 V/V/V)/TLC-SG systems respectively for quantification of {sup 99m}TcO{sub 4} - and {sup 99m}TcO{sub 2} plus some {sup 99m}Tc-DMSA complexes. The labeling activity did not significantly affect the extent of the main complex generation. The presence of oxygen and the concentration of {sup 99}Tc did not markedly change the percentage of the radiochemical impurities in the preparation. Radiochemical purity tests of the DMSA-{sup 99m}Tc based on IPEN-CNEN DMSA-TEC reagent and on another producer's reagent showed similar results. Although the routine method used by IPEN-CNEN to determine the radiochemical yield of {sup 99m}Tc-DMSA was not able to discriminate among {sup 99m}Tc-DMSA complexes, the renal uptake and the kidney to liver plus spleen uptake ratio in rats met the official compendia criteria for the radiopharmaceutical. (author)

Study of "9"9"mTc-DMSA biodistribution in experimental animals

International Nuclear Information System (INIS)

Castro, Thais O.M. de; Silva, Natanael G. da; Colturato, Maria T.; Felgueiras, Carlos F.; Mengatti, Jair; Fukumori, Neuza T.O.; Matsuda, Margareth M.N.; Araújo, Elaine B. de

2017-01-01

"9"9"mTc-DMSA, succimer ("9"9"mTc), is a radiopharmaceutical commonly used in nuclear medicine for renal function evaluation by imaging. In order to achieve adequate labeling of the product with good radiochemical yield and standardized biological distribution, the interval of 185 - 3700 MBq should be kept in a maximum volume of 3 mL for product labeling. Moreover, one should avoid exposing the reconstituted solution to oxygen and using the product after four hours post labeling. The aim of the study was to quantify and evaluate the influence of different DMSA complexes on biological distribution of the radiopharmaceutical in experimental animals, taking in account variations in the labeling parameters. Radiochemical purity was determined by paper and thin layer chromatography using both acetone/Whatman 3MM, 0.9% NaCl/TLC-SG and n-propanol/ H_2O/acetic acid (4:3:1 V/V/V)/TLC-SG systems respectively for quantification of "9"9"mTcO_4 - and "9"9"mTcO_2 plus some "9"9"mTc-DMSA complexes. The labeling activity did not significantly affect the extent of the main complex generation. The presence of oxygen and the concentration of "9"9Tc did not markedly change the percentage of the radiochemical impurities in the preparation. Radiochemical purity tests of the DMSA-"9"9"mTc based on IPEN-CNEN DMSA-TEC reagent and on another producer's reagent showed similar results. Although the routine method used by IPEN-CNEN to determine the radiochemical yield of "9"9"mTc-DMSA was not able to discriminate among "9"9"mTc-DMSA complexes, the renal uptake and the kidney to liver plus spleen uptake ratio in rats met the official compendia criteria for the radiopharmaceutical. (author)

The preparation and biodistribution of a new 99Tcm-nitrito complex 99TcmN-MIBI

International Nuclear Information System (INIS)

Zhang Xianzhong; Wang Xuebin; Zhang Junbo

1997-01-01

The technetium-99m nitrito intermediate is synthesized by using SnCl 2 ·2H 2 O as reductant, and the complex 99 Tc m N-MIBI is obtained through ligand exchange reaction. The labelling yield of 99 Tc m N-MIBI is over 95% by TLC. The conditions of preparing 99 Tc m N-MIBI are optimized. Results of stability and partition coefficient of 99 Tc m N-MIBI indicate that the complex is lipophilic and stable over 10 h at room temperature. The biodistribution of 99 Tc m N-MIBI in mice shows high myocardium uptake, and rather rapid clearance. For 5-min post-injection the heart-to-blood, heart-to-lung and heart-to-liver ratios are 3.18, 1.72 and 1.42, respectively. The new complex may be suitable for instant myocardial imaging. 99 Tc m N-MIBI has significant different biodistribution characteristics from 99 Tc m -MIBI. Based on these promising properties, 99 Tc m N-MIBI should be a new potential myocardial perfusion imaging agent

Influence of iron deficiency in the radiopharmaceutical behavior of red blood cells labeled with 99mTc(99mTC-RBC)

International Nuclear Information System (INIS)

Calmanovici, G.; Salgueiro, M.J.; Pernas, L.; Collia, N.; Leonardi, N.; Zubillaga, M.

2005-01-01

Full text: Red blood cells (RBCs) labeled with 99m Tc are commonly used in the evaluation of cardiac function, gastrointestinal tract bleeding, red blood cell volume or splenic sequestration. Generally stannous ion is used as reducing agent. A proposed mechanism is that once the stannous ion (Sn) and the pertechnetate ( 99m Tc) reach the interior of the RBC, the radionuclide is mainly house in the β-chain of hemoglobin. The aim of this study was to determine if hemoglobin content reduction, an indicator of iron deficiency anemia, could affect the efficiency of RBC labeling and the biological distribution of this radiopharmaceutical. We studied 30 rats fed for 3 weeks after weaning with diets with iron contents of 6.5 ppm (group A), 18 ppm (group B) and 100 ppm (control). For all groups, the labeling yields were always higher than 97%; the percentage of radioactivity was mostly founded in blood with almost negligible radioactivity the rest of the studied organs. We can conclude that the decrease in hemoglobin content, an indicator of iron deficiency anemia, does not interfere neither in the labeling nor in the biodistribution of red blood cells labeled with 99m Tc. (author)

The use of 99Mo/99mTc generators in the analysis of low levels of 99Tc in environmental samples by radiochemical methods

International Nuclear Information System (INIS)

Dowdall, M.; Selnaes, Oe.G.; Lind, B.; Gwynn, J.P.

2010-01-01

The analysis of low levels of 99 Tc in environmental samples presents special challenges, particularly with respect to the selection of an appropriate and practicable chemical yield tracer. Of all the tracers available, 99m Tc eluted from 99 Mo/ 99m Tc generators appears to be the most practicable in terms of availability, ease of use and cost. These factors have led to an increase in the use of such generators for the provision of 99m Tc as yield tracer for 99 Tc. For the analysis of low levels ( 3 or kg) of 99 Tc in environmental samples, consideration must be given to the radiochemical purity of the tracer solution with respect to contamination with both 99 Tc and other radionuclides. Due to the variable nature of the extent of the interference from tracer solution to tracer solution, it is unwise to try and establish a correction factor for any single generator. The only practical solution to the problem therefore is to run a 'blank' sample with each batch of samples drawn from a single tracer solution. (LN)

Binding and clearance of Tc-99m pyrophosphate from the lungs of smokers and nonsmokers

International Nuclear Information System (INIS)

Isitman, A.T.; Effros, R.; Collier, B.D.; Palmer, D.W.; Krasnow, A.Z.; Hellman, R.S.; Hacker, A.; Berger, C.; Trembath, L.

1990-01-01

Both acute and chronic lung disorders that affect the alveolar epithelium increase the rate at which aerosolized Tc-99 m DTPA is cleared from the lungs. Transalveolar clearance of Tc-99 DTPA has been used to detect lung injury, but- because smokers have a much faster clearance rate of Tc-99m DTPA-this examination has been limited primarily to nonsmokers. The purpose of this paper is to determine if the clearance of a larger molecule, Tc-99m PYP (molecular weight by ultrafiltration between 1.000 and 3,000 daltons), is also accelerated by smoking. Clearances of each indicator were studies for 6 hours in eight normal nonsmoking subjects and seven (otherwise normal smokers)

Diversification in the Supply Chain of (99)Mo Ensures a Future for (99m)Tc.

Science.gov (United States)

Cutler, Cathy S; Schwarz, Sally W

2014-07-01

The uncertain availability of (99m)Tc has become a concern for nuclear medicine departments across the globe. An issue for the United States is that currently it is dependent on a supply of (99m)Tc (from (99)Mo) that is derived solely by production outside the United States. Since the United States uses half the world's (99)Mo production, the U.S. (99)Mo supply chain would be greatly enhanced if a producer were located within the United States. The fragility of the old (99)Mo supply chain is being addressed as new facilities are constructed and new processes are developed to produce (99)Mo without highly enriched uranium. The conversion to low-enriched uranium is necessary to minimize the potential misuse of highly enriched uranium in the world for nonpeaceful means. New production facilities, new methods for the production of (99)Mo, and a new generator elution system for the supply of (99m)Tc are currently being pursued. The progress made in all these areas will be discussed, as they all highlight the need to embrace diversity to ensure that we have a robust and reliable supply of (99m)Tc in the future. © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

99mTc gel generators based on zirconium molybdate-99Mo: III: Influence of preparatory conditions of zirconium molybdate-99Mo gel on generator performance

International Nuclear Information System (INIS)

Saraswathy, P.; Sarkar, S.K.; Arjun, G.; Ramamoorthy, N.; Nandy, S.K.

2004-01-01

The effect of subtle variations on zirconium molybdate- 99 Mo gel preparatory conditions, such as stoichiometry of reactants, pH of gel formation, conditioning of gel granules etc., prior to elution were investigated primarily to arrive at the conditions resulting in high 99m Tc release and minimal 99 Mo breakthrough upon elution with normal saline. Zirconium molybdate- 99 Mo gels were prepared by reacting solutions of Zr and Mo in mole ratios of 0.75-1.5. Both water and normal saline were used for gel disintegration, and the release of 99m Tc and 99 Mo from gel columns into eluates was compared. Sharper elution profile of 99m Tc, but with significantly higher 99 Mo breakthrough (5-8 times), was obtained when water alone was used for disintegration and elution, in comparison to when saline was used. Gels exhibiting optimum characteristics were found to be formed at a pH of 4-5 by reacting [Zr]: [Mo] in the mole ratio of 1.25: 1 and after drying, the product was dispersed into granules by disintegration with normal saline. 99m Tc elution efficiency was found to be ∝ 75% and 99 Mo breakthrough ∝ 0.05%. The elution profile was sharp when a 6 g gel column coupled to a 2 g acidic alumina column (to trap 99 Mo) was eluted with 6-9 ml normal saline. Generators containing upto 23 GBq 99 Mo were prepared, eluted extensively without changing the alumina column and found to provide pertechnetate of good quality, commensurate with hospital radiopharmacy requirements. (orig.)

29 CFR 99.400 - Responsibilities.

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Responsibilities. 99.400 Section 99.400 Labor Office of the... Pass-through Entities § 99.400 Responsibilities. (a) Cognizant agency for audit responsibilities... the report submission due date required by § 99.320(a). The cognizant agency for audit may grant...

Cyclotron Production of Technetium-99m

Science.gov (United States)

Gagnon, Katherine M.

Technetium-99m (99mTc) has emerged as the most widely used radionuclide in medicine and is currently obtained from a 99Mo/ 99mTc generator system. At present, there are only a handful of ageing reactors worldwide capable of producing large quantities of the parent isotope, 99Mo, and owing to the ever growing shutdown periods for maintenance and repair of these ageing reactors, the reliable supply 99mTc has been compromised in recent years. With an interest in alternative strategies for producing this key medical isotope, this thesis focuses on several technical challenges related to the direct cyclotron production of 99mTc via the 100Mo(p,2n)99mTc reaction. In addition to evaluating the 100Mo(p,2n)99mTc and 100Mo(p,x)99Mo reactions, this work presented the first experimental evaluation of the 100Mo(p,2n) 99gTc excitation function in the range of 8-18 MeV. Thick target calculations suggested that large quantities of cyclotron-produced 99mTc may be possible. For example, a 6 hr irradiation at 500 μA with an energy window of 18→10 MeV is expected to yield 1.15 TBq of 99mTc. The level of coproduced 99gTc contaminant was found to be on par with the current 99Mo/99mTc generator standard eluted with a 24 hr frequency. Highly enriched 100Mo was required as the target material for 99mTc production and a process for recycling of this expensive material is presented. An 87% recovery yield is reported, including metallic target preparation, irradiation, 99mTc extraction, molybdate isolation, and finally hydrogen reduction to the metal. Further improvements are expected with additional optimization experiments. A method for forming structurally stable metallic molybdenum targets has also been developed. These targets are capable of withstanding more than a kilowatt of beam power and the reliable production and extraction of Curie quantities of 99mTc has been demonstrated. With the end-goal of using the cyclotron-produced 99mTc clinically, the quality of the cyclotron

Influence of plants on the distribution and composition of PBDEs in soils of an e-waste dismantling area: Evidence of the effect of the rhizosphere and selective bioaccumulation

International Nuclear Information System (INIS)

Wang, Yan; Luo, Chunling; Li, Jun; Yin, Hua; Zhang, Gan

2014-01-01

Rhizosphere effects on the distribution of PBDEs in e-waste contaminated soils were investigated. The geometric means of the PBDEs in the rhizosphere and non-rhizosphere soils were 32.6 ng/g and 12.2 ng/g, whereas the geometric means of the PBDEs in vegetable shoots and roots were 2.15 ng/g and 3.02 ng/g, respectively. PBDEs in soil at different distances from the root surface may first rise appreciably and then decrease to a non-rhizosphere level for long-term contaminated soils. Different PBDE compositions in roots and shoots indicated that PBDEs in shoots may be mainly taken up from the air. The ratios of BDE99/100 and BDE153/154 in plants and their corresponding soils were different. The bioaccumulations of BDEs 100 and 154 were much higher than those of BDEs 99 and 153, respectively. This indicated that the bioaccumulation was selective and influenced by the substitution pattern, with ortho-substituted isomers being more prevalent than meta-substituted isomers. -- Highlights: • PBDEs in rhizosphere soils were higher than those in non-rhizosphere soils. • PBDEs in soil may first be accumulated and then reduced towards root surface. • Bioaccumulation of PBDEs is selective and influenced by substituent effect. • Bioaccumulations of BDEs 100 and 154 were much higher than BDEs 99 and 153. -- The bioaccumulation of PBDE isomers was selective and influenced by the substituent effect, with ortho-substitution being favored over meta-substitution

Do temporal and geographical patterns of HBCD and PBDE flame retardants in U.S. fish reflect evolving industrial usage?

Science.gov (United States)

Chen, Da; La Guardia, Mark J; Luellen, Drew R; Harvey, Ellen; Mainor, T Matteson; Hale, Robert C

2011-10-01

Polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCD) are common flame retardants in polymers and textiles. Recognition of the persistent, bioaccumulative, and toxic properties of PBDEs has prompted reductions in their use. In contrast, HBCD has received less scrutiny. The U.S has historically been a dominant BFR consumer. However, the few publications on HBCD in wildlife here suggest modest levels compared to Asian and European studies. In contrast, the HBCD concentrations we detected in U.S. fish are among the highest reported in the world. The temporal trends observed suggest that HBCD use may have risen, and that of Penta-BDE declined, following the 2004 termination of its U.S. manufacture. For example, Hyco River carp collected in 1999-2002 exhibited a mean ∑HBCD (sum of α-, β- and γ-HBCD) concentration of only 13 ng/g (lipid weight basis), but was 4640 ng/g in fish collected in 2006-2007. In contrast, the mean ∑PBDE level in these same fish decreased from 40,700 ng/g in 1999-2002 to 9140 ng/g in 2006-2007. Concentrations of HBCD and PBDEs in several Hyco River fish species exceeded those from rivers less influenced by manufacturing outfalls. Results support the contention that textile-related production, relative to its BFR market share, may release disproportionately large amounts of HBCD to the environment.

Comparison of 99Tcm(V)-DMSA and 99Tcm-MIBI scintigraphy in medullary thyroid carcinoma

International Nuclear Information System (INIS)

Deng Bo; Xiao Huan; Chen Xiaofeng; Chen Huaming

2004-01-01

SPECT scintigraphy is used in 62 patients with medullary thyroid carcinoma (MTC), which are divided into two groups: 32 patients by 99 Tc m (V)-DMSA and 30 patients by 99 Tc m -MIBI. The qualitative analysis and half quantitative analysis are performed to the early and delayed images. Comparing the results with two groups, there is no difference in the masculine rate of MTC primary focus, but the results of 99 Tc m (V)-DMSA scintigraphy is obviously larger than 99 Tc m -MIBI by half quantitative analysis. The results show that the 99 Tc m (V)-DMSA scintigraphy is more predominant than the 99 Tc m -(V)-DMSA scintigraphy may be superior to 99 Tc m -MIBI in MTC primary focus and metastasis focus before surging for MTC patients. (authors)

Effect of collagen I and fibronectin on the adhesion, elasticity and cytoskeletal organization of prostate cancer cells.

Science.gov (United States)

Docheva, Denitsa; Padula, Daniela; Schieker, Matthias; Clausen-Schaumann, Hauke

2010-11-12

Despite of intensive research efforts, the precise mechanism of prostate cancer metastasis in bone is still not fully understood. Several studies have suggested that specific matrix production by the bone cells, such as collagen I, supports cancer cell invasion. The aim of this study was to investigate the effect of collagen I (COL1) and fibronectin (FN) on cell adhesion, cell elasticity and cytoskeletal organization of prostate cancer cells. Two cell lines, bone marrow- (PC3) and lymph node-derived (LNCaP) were cultivated on COL1 and FN (control protein). By using a quantitative adhesion assay and time-lapse analysis, it was found that PC3, but not LNCaP, adhered strongly and were more spread on COL1. Next, PC3 and LNCaP were evaluated by atomic force microscopy (AFM) and flatness shape factor and cellular Young's modulus were calculated. The shape analysis revealed that PC3 were significantly flatter when grown on COL1 in comparison to LNCaP. In general, PC3 were also significantly stiffer than LNCaP and furthermore, their stiffness increased upon interaction with COL1. Since cell stiffness is strongly dependent on actin organization, phalloidin-based actin staining was performed and revealed that, of the two cell types as well as the two different matrix proteins, only PC3 grown on COL1 formed robust actin cytoskeleton. In conclusion, our study showed that PC3 cells have a strong affinity towards COL1. On this matrix protein, the cells adhered strongly and underwent a specific cell flattening. Moreover, with the establishment of PC3 contact to COL1 a significant increase of PC3 stiffness was observed due to a profound cytoskeletal rearrangement. Copyright © 2010 Elsevier Inc. All rights reserved.

Generator of {sup 99m} Tc with MnO{sub 2} as support of {sup 99} Mo; Generador de {sup 99m} Tc con MnO{sub 2} como soporte del {sup 99}Mo

Energy Technology Data Exchange (ETDEWEB)

Granados C, F.; Serrano G, J. [Departamento de Quimica, Instituto Nacional de Investigaciones Nucleares, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

2002-07-01

The generator of {sup 99m} Tc with MnO{sub 2} as support of {sup 99} Mo was studied. By mean of static experiments the retention of {sup 99} Mo in MnO{sub 2} in function of the stirring time and of the p H value of the solution of {sup 99} Mo. It was found that the {sup 99} Mo presents 100% of retention in MnO{sub 2} in the rank of p H 3-11 and the balance was reached before of 10 minutes. In dynamic conditions the retention of {sup 99} Mo in MnO{sub 2} at p H=5 was also higher: 99.72%. The generated {sup 99m} Tc can be separated from {sup 99} Mo, adsorbed in MnO{sub 2} packed in the column, using distilled water at p H=5 or NaCl solution at 0.9%. With saline solution the elution yields were greater than 80% and only an aliquot of 5 ml was necessary for obtaining this yield. The better results were obtained when the column was packed with 1 g of MnO{sub 2}. The water and the saline solution were passed through of the column with a flux of 1.25 ml/min. (Author)

Study of the elution 99Mo-99mTc generators produced at IPEN-CNEN/SP

International Nuclear Information System (INIS)

Lopes, Paula Regina Corain; Osso Junior, Joao Alberto

2007-01-01

Over the last years 99m Tc has become a very important asset in modern nuclear medicine, due to the emission of gamma ray of optimal energy (140 keV) and a suitable half-life (6.04 h). A further attribute of 99m Tc is its formation from the decay of 99 Mo and the availability from 99 Mo- 99m Tc generator systems. The most common and practical generator types consist of a chromatographic column packed with aluminium oxide, onto which the highly purified fission product 99 Mo (imported from Canada) is adsorbed in the form of molybdate. 99m Tc is further eluted with saline solution. The objective of this work is to study the performance and the elution profile of 99m Tc from high activity generators in order to decrease molybdenum and aluminium concentration. The experiments involved the use of paper filters and Sep Pak columns and also the changing in the time interval between elutions. 99 Mo breakthrough was measured using a dose calibrator and aluminium by UV-Vis spectrophotometry. The best results were achieved using a Sep Pak column containing neutral aluminium oxide. (author)

99mTc-Tetrofosmin scintimammography in suspected breast cancer patients: comparison with 99mTc-MIBI

International Nuclear Information System (INIS)

Kim, Seong Jang; Kim, In Ju; Kim, Yong Ki; Bae, Young Tae

2000-01-01

The aim of this study was to investigate the diagnostic role of 99m Tc-Tetrofosmin in detection of breast cancer and compared with that of 99m Tc-MIBI. Forty-eight patients with a clinically palpable mass or abnormal mammographic or ultrasonographic findings had 99m Tc-MIBI and 99m Tc-Tetrofosmin scintimammographies after intravenous injection of 925 MBq of radiopharmaceuticals. The scintimammographs were correlated with histopathologic findings. Thirty-three patients were diagnosed with breast cancer and 15 patients with benign breast diseases. The numbers of true positive, true negative, false positive, and false negative cases of 99m Tc-MIBI scintimammography were 29, 10, 5, and 4 respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of 99m Tc-MIBI scintimammographies were 87.8%, 66.7%, 85.3%, and 71.4% respectively. The numbers of true positive, true negative, false positive, and false negative cases of 99m Tc-Tetrofosmin were 31, 10, 5, and 2 respectively. The sensitivity, specificity, positive predictive value, negative predictive value of 99m Tc-Tetrofosmin were 93.9%, 66.7%, 86.1%, and 73.3% respectively. One patient was false negative in both 99m Tc-Tetrofosmin scintimammographies and its size was 0.5cm. 99m Tc-Tetrofosmin and 99m Tc-MIBI were non-invasive and useful in detection of breast cancer and 99m Tc-Tetrofosmin was comparable to the 99m Tc-MIBI in detection of primary breast cancer.=20

Quantification of ionic-channel abnormalities in cancer cells using 99mTc-diisopropyliminodiacetic acid (DISIDA)

International Nuclear Information System (INIS)

Yoon, Eun Jeong; Jang, Yoo Jueng; Kim, Nae Hyun; Kim, Meyoung Kon

2001-01-01

Ion channels and intracellular concentration of Ca 2+ or K + are thought to be involved in cell proliferation and tumor development. To measure the ionic-channel abnormalities in a quantitative manner, we used ionic-channel gated hepatobiliary imaging agents such as 99m Tc-DISIDA and 99m Tc-MAG3-biocytin. For in vivo study, dynamic images showed that 99m Tc-DISIDA coinjected with bilirubin had a higher blood background and a lower hepatic uptake than 99m Tc-DISIDA alone, whereas 99m Tc-MAG3-biocytin did not affected by bilirubin coinjection. For in vitro study, the cellular uptake of 5 different types of human cancer cells were ranked as follows: SK Mel-1 (melanoma), MCF-7 (breast adenocarcinoma), Jurkat (T-cell leukemia), SK-Mel-2 (melanoma), and HL-60 (polymyelocytic leukemia). In summary, these results demonstrated that the combination of 99m Tc-DISIDA and SK-Mel-1 is the most appropriate system for evaluation in ionic-channel abnormalities of cancer cells

29 CFR 99.105 - Definitions.

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Definitions. 99.105 Section 99.105 Labor Office of the Secretary of Labor AUDITS OF STATES, LOCAL GOVERNMENTS, AND NON-PROFIT ORGANIZATIONS General § 99.105 Definitions. Audit finding means deficiencies which the auditor is required by § 99.510(a) to report in the...

Validation of alternative methods of preparing {sup 99m}Tc-MAG3

Energy Technology Data Exchange (ETDEWEB)

Seetharaman, Shankar [Department of Pharmacy, Guy' s and St Thomas' Hospital, Lambeth Palace Road, London SE1 9EH (United Kingdom); Sosabowski, Michael H. [School of Pharmacy and Biomolecular Sciences, University of Brighton, Moulsecoomb (United Kingdom); Ballinger, James R. [Department of Nuclear Medicine, Guy' s and St Thomas' Hospital, St Thomas Street, London SE1 9RT (United Kingdom)], E-mail: james.ballinger@gstt.nhs.uk

2007-11-15

Parameters in the preparation of {sup 99m}Tc-mertiatide ({sup 99m}Tc-MAG3) were investigated to determine the importance of total activity, activity concentration, boiling time, and delay before boiling for the radiochemical purity (RCP) and stability of the product. Satisfactory RCP results (>90%) were obtained over a range of concentrations including a dilute preparation for paediatric use. RCP was not affected by the time between the addition of pertechnetate and boiling, but low RCP (<60%) resulted when the kit was boiled for less than 10 min.

Preparation of clinical-scale 99Mo/99mTc column generator using neutron activated low specific activity 99Mo and nanocrystalline γ-Al2O3 as column matrix.

Science.gov (United States)

Chakravarty, Rubel; Ram, Ramu; Dash, Ashutosh; Pillai, M R A

2012-10-01

Preparation of clinical-scale (99)Mo/(99m)Tc generator using (n,γ) activated low specific activity (99)Mo and nanocrystalline γ-Al(2)O(3) as a high capacity sorbent matrix is attempted. Nanocrystalline γ-Al(2)O(3) was synthesized by 'solid state mechanochemical' reaction of aluminum nitrate with ammonium bicarbonate. Experimental parameters were optimized to effectively separate (99m)Tc from (99)Mo using this sorbent as the column matrix. The performance features of a 13 GBq (350 mCi) (99)Mo/(99m)Tc generator using this sorbent and (99)Mo produced by (n,γ) route having specific activity 12.9-18.5 GBq/g were evaluated for 10 days. The sorbent possessed the requisite selectivity for (99)Mo and demonstrated a maximum sorption capacity of 200 ± 5mg Mo/g, which is ~10 times higher than that of ordinary acidic alumina. The overall yield of (99m)Tc was >80%, with radionuclidic purity >99.99% and radiochemical purity >99%. The yield of (99m)Tc varied from 7.8 to 2.1 GBq in the eluate for the six days of operation of the generator. The radioactive concentration of (99m)Tc eluted was adequate for the formulation of radiopharmaceuticals. The performance of the generator remained consistent over an extended period of 10 days. The eluted (99m)Tc was suitable for the formulation of (99m)Tc-DMSA and (99m)Tc-EC resulting in high radiolabeling yields (>98%). The effectiveness of γ-Al(2)O(3) as a new generation sorbent in the development of clinically useful (99)Mo/(99m)Tc generator using low specific activity (99)Mo and yielding (99m)Tc with adequate radioactive concentration and high purity suitable for formulation of radiopharmaceuticals is demonstrated. Copyright © 2012 Elsevier Inc. All rights reserved.

Quality control studies of {sup 99}Mo used in {sup 99}Mo/{sup 99m}Tc generators produced at IPEN/CNEN-SP, Brazil

Energy Technology Data Exchange (ETDEWEB)

Said, Daphne S.; Brambilla, Tania P.; Matsuda, Margareth M.N.; Osso Junior, Joao A., E-mail: daphnesaid@usp.br, E-mail: taniabrambilla@yahoo.com.br, E-mail: mmatsuda@ipen.br, E-mail: jaosso@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2015-07-01

{sup 99m}Tc is the most used radionuclide in nuclear medicine. In Brazil, the {sup 99}Mo/{sup 99m}Tc generators are produced exclusively by the Center of Radiopharmacy at IPEN-CNEN/SP, by importing {sup 99}Mo from different suppliers. {sup 99}Mo (t{sub 1/2} = 66 h) is a fission product of {sup 235}U, therefore, it can be accompanied by several radioisotopes that are highly prejudicial for human health, demanding a strict quality control of this product for generators safe use. The European Pharmacopoeia established some parameters and limits that evaluate the quality of the solution of sodium [{sup 99}Mo]molybdate, that is used as raw material for generator's production. The European Pharmacopoeia also recommends some analytical methods to perform these evaluations, however, it has been observed difficulties on the implementation of these methods by the generator's producers. These difficulties are probably related to the lack of practicability of the proposed methods and the extensive list of utilized reagents. In this work some procedures of the European Pharmacopoeia's quality control method for {sup 99}Mo were evaluated. Different types of solid phase exchanger cartridges were tested for retention of {sup 99}Mo in 3 different conditions. Cartridges that presented percentages of retention higher than 90% were also tested for separation of {sup 99}Mo from possible contaminants (Ru e Te). The results shown that solid phase exchanger cartridges that presented percentages of retention of Mo higher than 90% also presented significant percentages of retention of Ru and Te. An alternative method for separation of {sup 99}Mo from {sup 131}I (other contaminant) are also proposed. (author)

A {sup 99m}Tc Generator using PZC for (n,{gamma}) {sup 99}Mo

Energy Technology Data Exchange (ETDEWEB)

Adang, H G; Mutalib, A; Suparman, I; Hamid,; Purwadi, B; Pancoko, M; Setiowati, S; Yulianti, V; Robertus, D H [Radioisotope Production Center, National Atomic Energy Agency Kawasan PUSPIPTEK, Serpong (Indonesia)

1998-10-01

The high performance adsorbent Poly Zirconium Compound (PZC) was produced by Department of Radioisotope, Japan Atomic Energy Research Institute. This compound was developed as an adsorbent for natural Mo (n,{gamma}) {sup 99}Mo-{sup 99m}Tc Generator. In the present paper, we report the performance of the PZC for a {sup 99m}Tc Generator which was focused on the yield, on elution profile and {sup 99}Mo breakthrough. (author)

Targeting osteomyelitis with complete [99mTc]besilesomab and fragmented [99mTc]sulesomab antibodies: kinetic evaluations

International Nuclear Information System (INIS)

GRATZ, Stefan; KEMKE, Bendix; KEIZE, Patrik; KAMPEN, Wim U.; LUSTER, Markus; HÖFFKEN, Helmut

2016-01-01

The aim of this retrospective study was to compare the targeting of “pure” osteomyelitis (i.e., without surrounding soft tissue infection) by directly 99mTc-labelled complete immunoglobulin G (IgG) monoclonal antibody (MAb) ([99mTc]besilesomab) and by directly 99mTc-labelled fragment antigen-binding (FAb) MAb ([99mTc]sulesomab) in relation to their kinetic fate. A total of 73 patients with “pure” osteomyelitis were examined with [99mTc]besilesomab, (Scintimun®, IBA/CIS bio international, Saclay, France; N.=38) and [99mTc]sulesomab (LeukoScan®, Immunomedics Inc., Morris Plains, NJ, USA; N.=35). Kinetic data were deduced from whole-body and single-photon emission computed tomographic scans, performed 10 minutes to 24 hour p.i. (region-of-interest technique [ROI]). In targeting “pure” osteomyelitis, sensitivities at 1-4 hours were found to be higher for [99mTc]sulesomab (44% and 80% for [99mTc]besilesomab and [99mTc]sulesomab, respectively) but at significantly lower target/background (T/B) ratios than with [99mTc]besilesomab (1.8±0.3 versus 1.4±0.5 for [99mTc]besilesomab and [99mTc]sulesomab respectively; P<0.01). With [99mTc]besilesomab, there was a continuous osteomyelitis uptake over 24 hours, whereas with [99mTc]sulesomab, the maximal uptake occurred mostly within 1-4 hours, with subsequent clearance being slower for antigen-bound activity than for nonspecific background. Hence, diagnosis was possible mostly after 4h with [99mTc]sulesomab but often not before 24 hours with [99mTc]besilesomab, the later increasing significantly (P<0.01) in sensitivity (87% and 84% for [99mTc]besilesomab and [99mTc]sulesomab, respectively). These results show that the higher sensitivity of [99mTc]sulesomab in osteomyelitis targeting at earlier p.i. times does not rely on an increased antibody uptake but on a more rapid clearance of nonspecific background activity due to faster metabolism and excretion. Intact [99mTc]besilesomab show a slow, continuous uptake

Chemical aspects of labeling sucralfate with /sup 99m/TcO/sub 4/

Energy Technology Data Exchange (ETDEWEB)

Billinghurst, M.W.; Abrams, D.N.; Lawson, M.S.

1989-04-01

Two formulations of (/sup 99m/Tc)sucralfate have been used to image gastric and duodenal ulcers and inflammatory bowel disease. One formulation is a complexation of (/sup 99m/Tc)HSA with sucralfate. The second is prepared by directly labeling sucralfate with (/sup 99m/Tc)pertechnetate in the presence of stannous ion. An in vitro study of the factors affecting the production and stability of these labeled sucralfate preparations was conducted. Both formulations were stable at the acidic pH likely encountered in the stomach. However, at pH greater than 6 the albumin-sucralfate complex began to dissociate while directly labeled sucralfate was stable to a pH of 9. Conversely it was shown that directly labeled sucralfate was more susceptible to loss of /sup 99m/Tc to other chelating species. Sucralfate complexed with (/sup 99m/Tc)HSA was radiochemically stable up to a specific activity of 26 GBq (700 mCi) per gram while directly labeled sucralfate showed decreased 24-hr stability at specific activities greater than 837 mCi (31 GBq) per gram.

Alteration of 99mTc-DMSA biodistribution in glomerulonephritis

International Nuclear Information System (INIS)

Rajic, M.; Bogicevic, M.; Ilic, S.; Vlajkovic, M.; Antic, S.; Mitic, B.; Avramovic, M.; Mitic-Zlatovic, M.; Stefanovic, V.

2002-01-01

The aim of this study was to assess the relation between 99T c-DMSA biodistribution and its reliability as a marker of renal function in patients with glomerular kidney diseases. Sixty-seven patients involved in this study were classified into two groups according to 99T c-DTPA clearance and serum creatinine values: the 1. group consisted of 42 patients without renal failure while the 2nd group included 25 patients with renal failure. 99T c-DMSA biodistribution was determined by measuring kidney, blood and urine activity at 2 h and 4 h. The results, compared with those of 23 healthy volunteers, indicated the quantitative alteration of 99T c-DMSA distribution in both glomerulonephritis patient groups. In reference to the control mean values of 2 h and 4 h, in patients without renal failure, kidney activity was found decreased to 52% and 57%, while the blood activity increase of 37% and 44% was recorded together with the urine activity increase of 38% and 23%. In patients with renal failure the alterations of renal and blood activity were more remarkable, but the urine loss was found to be unchanged. It is suggested that these biodistribution changes originate mainly from tubular impairment. However, in glomerulonephritis patients, altered glomerular filtration might considerably affect biodistribution of this radiopharmaceutical and limits its suitability for precise quantitative estimation of renal function. (author)

Method of producing molybdenum-99

Science.gov (United States)

Pitcher, Eric John

2013-05-28

Method of producing molybdenum-99, comprising accelerating ions by means of an accelerator; directing the ions onto a metal target so as to generate neutrons having an energy of greater than 10 MeV; directing the neutrons through a converter material comprising techentium-99 to produce a mixture comprising molybdenum-99; and, chemically extracting the molybdenum-99 from the mixture.

Probabilistic risk assessment of the exposure to polybrominated diphenyl ethers via fish and seafood consumption in the Region of Valencia (Spain).

Science.gov (United States)

Pardo, Olga; Beser, Maria Isabel; Yusà, Vicent

2014-06-01

The study was carried out to estimate the dietary intake of polybrominated diphenyl ethers (PBDEs) in the Region of Valencia (Spain) in order to evaluate the resultant risk. The PBDE levels in fish and seafood (a total of 206 samples) were determined. Dietary intake was estimated using results of PBDE analyses in fish and seafood marketed in the Region of Valencia over the period 2007-2012 and data of the first Valencian Food Consumption Survey, conducted in 2010. Two scenarios were assumed for left-censored results: the lower-bound (LB) scenario, in which unquantified results (below the limit of quantification (LOQ)) were set to zero and the upper-bound (UB) scenario, in which unquantified results were set to the LOQ and two approaches (deterministic and probabilistic) were compared. The mean PBDE concentration in fish and seafood from Valencian markets was between 0.97 and 3.87 ngg(-1) w.w. and was similar to that reported recently by European Food Safety Authority (EFSA). Among the analysed congeners, BDE-47 showed the highest levels and salmon, mackerel and swordfish were the most contaminated species. The average estimated daily intake of the sum of PBDEs (upper bound scenario; probabilistic approach) for adults and children were 0.137 ngkg(-1) body weight (b.w.) day and 0.180 ngkgb.w.(-1)d(-1), respectively. In relation to risk analysis, calculated margins of exposure (MOEs) for the BDE-47, -99 and -153 congeners for children and do not indicate a health concern with respect to current dietary exposure in the Valencian Region and only 0.05% of the adult population and a 0.1% of children could be in risk derived by BDE-99 intake through fish. Copyright © 2014 Elsevier Ltd. All rights reserved.

PBDEs in the atmosphere over the Asian marginal seas, and the Indian and Atlantic oceans

Science.gov (United States)

Li, Jun; Li, Qilu; Gioia, Rosalinda; Zhang, Yanlin; Zhang, Gan; Li, Xiangdong; Spiro, Baruch; Bhatia, Ravinder S.; Jones, Kevin C.

2011-12-01

Air samples were collected from Jan 16 to Mar 14, 2008 onboard the Oceanic II- The Scholar Ship which navigated an east-west transect from Shanghai to Cape Verde, and polybrominated diphenyl ethers (PBDEs) were analyzed in these samples. PBDE concentrations in the atmosphere over the open seas were influenced by proximity to source areas and land, and air mass origins. The concentrations of Σ 21PBDEs over the East and South China Seas, the Bay of Bengal and the Andaman Sea, the Indian Ocean, and the Atlantic Ocean were 10.8 ± 6.13, 3.22 ± 1.57, 5.12 ± 3.56, and 2.87 ± 1.81 pg m -3, respectively. BDE-47 and -99 were the dominant congeners in all the samples, suggesting that the widely used commercial penta-BDE products were the original sources. Over some parts of Atlantic and Indian Ocean, daytime concentrations of BDE-47 and BDE-99 were higher than the concentrations at night. The strong atmospheric variability does not always coincide with a diurnal cycle, but the variability in air concentrations in such remote areas of the ocean remains strong. No significant trends were found for each of PBDE congener with latitude.

Concentrations and distribution of polybrominated diphenyl ethers (PBDEs) in soils and plants from a deca-BDE manufacturing factory in China.

Science.gov (United States)

Li, Yuan; Niu, Shan; Hai, Reti; Li, Meng

2015-01-01

Residues of polybrominated diphenyl ethers (PBDEs), including eight PBDE congeners, were investigated in soils and plants from a deca-BDE manufacturing factory located in the Shandong province of China to evaluate and discuss their pollution level and distribution. Total concentrations in topsoil ranged from 17.0 to 146 μg g(-1) dry weight (dw) with a mean value of 58.7 μg g(-1) dw. BDE-209 was the dominant congener in soils, accounting for 55.63-99.27 % of the total PBDEs. Concentrations and congener patterns in soils varied among different soil depths. Concentration levels in topsoil are high and the heavy accumulation in deep soil also can be observed, even for some sites, the concentrations in 50-100 cm depth are higher than in topsoil. In plant samples, total PBDE concentrations and the proportion of BDE-209 were high (69.92-99.10 %). The extent of pollution by PBDEs in the deca-BDE production factory was higher than in other regions, and the environmental risk caused by the production of deca-BDE is of concern. This is the first study to report pollution of PBDEs in soils and plants from the vicinity of a deca-BDE manufacturing factory.

Development of a multichemical food web model: application to PBDEs in Lake Ellasjoen, Bear Island, Norway.

Science.gov (United States)

Gandhi, Nilima; Bhavsar, Satyendra P; Gewurtz, Sarah B; Diamond, Miriam L; Evenset, Anita; Christensen, Guttorm N; Gregor, Dennis

2006-08-01

A multichemical food web model has been developed to estimate the biomagnification of interconverting chemicals in aquatic food webs. We extended a fugacity-based food web model for single chemicals to account for reversible and irreversible biotransformation among a parent chemical and transformation products, by simultaneously solving mass balance equations of the chemicals using a matrix solution. The model can be applied to any number of chemicals and organisms or taxonomic groups in a food web. The model was illustratively applied to four PBDE congeners, BDE-47, -99, -100, and -153, in the food web of Lake Ellasjøen, Bear Island, Norway. In Ellasjøen arctic char (Salvelinus alpinus), the multichemical model estimated PBDE biotransformation from higher to lower brominated congeners and improved the correspondence between estimated and measured concentrations in comparison to estimates from the single-chemical food web model. The underestimation of BDE-47, even after considering bioformation due to biotransformation of the otherthree congeners, suggests its formation from additional biotransformation pathways not considered in this application. The model estimates approximate values for congener-specific biotransformation half-lives of 5.7,0.8,1.14, and 0.45 years for BDE-47, -99, -100, and -153, respectively, in large arctic char (S. alpinus) of Lake Ellasjøen.

99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-Q12 in vitro and in vivo

International Nuclear Information System (INIS)

Bernard, Bert F.; Krenning, Eric P.; Breeman, Wout A. P.; Ensing, Geert; Benjamins, Harry; Bakker, Willem H.; Visser, Theo J.; Jong, Marion de

1998-01-01

The aim of this study was to compare uptake of 99m Tc-MIBI, 99m Tc-tetrofosmin and 99m Tc-Q12 in vitro and biodistribution in vivo in rats. In vitro, uptake decreased in the order MIBI→tetrofosmin→Q12. Uptake of MIBI and tetrofosmin, but not of Q12, in cultured tumor cells was dependent on the plasma membrane and mitochondrial potential. In vivo, heart uptake of all three compounds was high and stable. Tumor uptake decreased in the order MIBI→Q12→tetrofosmin and the tumor/blood ratio in the order MIBI→tetrofosmin→Q12

Comparison of relative renal function measured with either 99m Tc-DTPA or 99m Tc-EC dynamic scintigraphies with that measured with 99m Tc-DMSA static scintigraphy

Energy Technology Data Exchange (ETDEWEB)

Domingues, F.C.; Fujikawa, G.Y.; Decker, H.; Alonso, G.; Pereira, J.C.; Duarte, P.S. [Centro de Diagnostico Fleury, Sao Paulo, SP (Brazil). Secao de Medicina Nuclear; Sao Paulo Univ. (USP), SP (Brazil). Escola de Saude Publica. Dept. de Epidemiologia]. E-mail: paulo.duarte@fleury.com.br

2006-07-15

Objective: The aim of this study was to compare the renal function measured with either {sup 99m}Tc-DTPA or {sup 99m}Tc-EC dynamic scintigraphies with that measured using {sup 99m}Tc-DMSA static scintigraphy. Methods: the values of relative renal function measured in 111 renal dynamic scintigraphies performed either with {sup 99m}Tc-DTPA (55 studies) or with {sup 99m}Tc-EC (56 studies) were compared with the relative function measured using {sup 99m}Tc-DMSA static scintigraphy performed within a 1-month period. The comparisons were performed using Wilcoxon signed rank test. The number of {sup 99m}Tc-DTPA and {sup 99m}Tc-EC studies that presented relative renal function different by more than 5% from that measured with {sup 99m}Tc-DMSA, using chi square test were also compared. Results: the relative renal function measured with {sup 99m}Tc-EC is not statistically different from that measured with {sup 99m}Tc-DMSA (p = 0.97). The relative renal function measured with {sup 99m}Tc-DTPA was statistically different from that measured using {sup 99m}Tc-DMSA, but with a borderline statistical significance (p = 0.05). The number of studies with relative renal function different by more than 5% from that measured with {sup 99m}Tc-DMSA is higher for the {sup 99m}Tc-DTPA scintigraphy (p 0.04) than for {sup 99m}Tc-EC. Conclusion: the relative renal function measured with {sup 99m}Tc-EC dynamic scintigraphy is comparable with that measured with {sup 99m}Tc-DMSA static scintigraphy, while the relative renal function measured with {sup 99m}Tc-DTPA dynamic scintigraphy presents a significant statistical difference from that measured with {sup 99m}Tc-DMSA static scintigraphy. (author)

Comparison of relative renal function measured with either 99m Tc-DTPA or 99m Tc-EC dynamic scintigraphies with that measured with 99m Tc-DMSA static scintigraphy

International Nuclear Information System (INIS)

Domingues, F.C.; Fujikawa, G.Y.; Decker, H.; Alonso, G.; Pereira, J.C.; Duarte, P.S.; Sao Paulo Univ.

2006-01-01

Objective: The aim of this study was to compare the renal function measured with either 99m Tc-DTPA or 99m Tc-EC dynamic scintigraphies with that measured using 99m Tc-DMSA static scintigraphy. Methods: the values of relative renal function measured in 111 renal dynamic scintigraphies performed either with 99m Tc-DTPA (55 studies) or with 99m Tc-EC (56 studies) were compared with the relative function measured using 99m Tc-DMSA static scintigraphy performed within a 1-month period. The comparisons were performed using Wilcoxon signed rank test. The number of 99m Tc-DTPA and 99m Tc-EC studies that presented relative renal function different by more than 5% from that measured with 99m Tc-DMSA, using chi square test were also compared. Results: the relative renal function measured with 99m Tc-EC is not statistically different from that measured with 99m Tc-DMSA (p = 0.97). The relative renal function measured with 99m Tc-DTPA was statistically different from that measured using 99m Tc-DMSA, but with a borderline statistical significance (p = 0.05). The number of studies with relative renal function different by more than 5% from that measured with 99m Tc-DMSA is higher for the 99m Tc-DTPA scintigraphy (p 0.04) than for 99m Tc-EC. Conclusion: the relative renal function measured with 99m Tc-EC dynamic scintigraphy is comparable with that measured with 99m Tc-DMSA static scintigraphy, while the relative renal function measured with 99m Tc-DTPA dynamic scintigraphy presents a significant statistical difference from that measured with 99m Tc-DMSA static scintigraphy. (author)

In-house cyclotron production of high-purity Tc-99m and Tc-99m radiopharmaceuticals.

Science.gov (United States)

Martini, Petra; Boschi, Alessandra; Cicoria, Gianfranco; Zagni, Federico; Corazza, Andrea; Uccelli, Licia; Pasquali, Micòl; Pupillo, Gaia; Marengo, Mario; Loriggiola, Massimo; Skliarova, Hanna; Mou, Liliana; Cisternino, Sara; Carturan, Sara; Melendez-Alafort, Laura; Uzunov, Nikolay M; Bello, Michele; Alvarez, Carlos Rossi; Esposito, Juan; Duatti, Adriano

2018-05-30

In the last years, the technology for producing the important medical radionuclide technetium-99m by cyclotrons has become sufficiently mature to justify its introduction as an alternative source of the starting precursor [ 99m Tc][TcO 4 ] - ubiquitously employed for the production of 99m Tc-radiopharmaceuticals in hospitals. These technologies make use almost exclusively of the nuclear reaction 100 Mo(p,2n) 99m Tc that allows direct production of Tc-99m. In this study, it is conjectured that this alternative production route will not replace the current supply chain based on the distribution of 99 Mo/ 99m Tc generators, but could become a convenient emergency source of Tc-99m only for in-house hospitals equipped with a conventional, low-energy, medical cyclotron. On this ground, an outline of the essential steps that should be implemented for setting up a hospital radiopharmacy aimed at the occasional production of Tc-99m by a small cyclotron is discussed. These include (1) target production, (2) irradiation conditions, (3) separation/purification procedures, (4) terminal sterilization, (5) quality control, and (6) Mo-100 recovery. To address these issues, a comprehensive technology for cyclotron-production of Tc-99m, developed at the Legnaro National Laboratories of the Italian National Institute of Nuclear Physics (LNL-INFN), will be used as a reference example. Copyright © 2018 Elsevier Ltd. All rights reserved.

The cytoskeletal inhibitors latrunculin A and blebbistatin exert antitumorigenic properties in human hepatocellular carcinoma cells by interfering with intracellular HuR trafficking

International Nuclear Information System (INIS)

Doller, Anke; Badawi, Amel; Schmid, Tobias; Brauß, Thilo; Pleli, Thomas; Meyer zu Heringdorf, Dagmar; Piiper, Albrecht; Pfeilschifter, Josef; Eberhardt, Wolfgang

2015-01-01

The impact of the RNA-binding protein HuR for the post-transcriptional deregulation of tumor-relevant genes is well established. Despite of elevations in HuR expression levels, an increase in cytoplasmic HuR abundance in many cases correlates with a high grade of malignancy. Here, we demonstrated that administration of the actin-depolymerizing macrolide latrunculin A, or blebbistatin, an inhibitor of myosin II ATPase activity, caused a dose- and time-dependent reduction in the high cytoplasmic HuR content of HepG2 and Huh7 hepatocellular carcinoma (HCC) cells. Subcellular fractionation revealed that in addition, both inhibitors strongly attenuated cytoskeletal and membrane-bound HuR abundance and conversely increased the HuR amount in nuclear cell fractions. Concomitant with changes in intracellular HuR localization, both cytoskeletal inhibitors markedly decreased the half-lives of cyclooxygenase-2 (COX-2), cyclin A and cyclin D 1 encoding mRNAs resulting in a significant reduction in their expression levels in HepG2 cells. Importantly, a similar reduction in the expression of these HuR targets was achieved by a RNA interference (RNAi)-mediated knockdown of either HuR or nonmuscle myoin IIA. Using polysomal fractionation, we further demonstrate that the decrease in cytoplasmic HuR by latrunculin A or blebbistatin is accompanied by a marked change in the allocation of HuR and its mRNA cargo from polysomes to ribonucleoprotein (RNP) particles. Functionally, the basal migration and prostaglandin E 2 synthesis are similarly impaired in inhibitor-treated and stable HuR-knockdown HepG2 cells. Our data demonstrate that interfering with the actomyosin-dependent HuR trafficking may comprise a valid therapeutic option for antagonizing pathologic posttranscriptional gene expression by HuR and furthermore emphasize the potential benefit of HuR inhibitory strategies for treatment of HCC. - Highlights: • We tested the effects of latrunculin A and blebbistatin on different Hu

Evaluation of '99Mo presence in eluates of 99mTc used in nuclear medicine

International Nuclear Information System (INIS)

Ribeiro, Bianca da Silva

2010-01-01

Tc-99m is used for diagnostic imaging in nuclear medicine through SPECT technique. It is obtained by the elution of 99 Mo/ 99m Tc generators. During the elution process 99 Mo can be extracted becoming a radionuclidic impurity. One of the quality parameters of the eluate is the radionuclidic purity, MBT (molybdenum break through), defined as the ratio between 99 Mo and 99m Tc activities in the eluate. The North-American and European pharmacopoeias restrict the 99 Mo content, respectively, in 0.015 e 0.1% and, according to the International Atomic Energy Agency (IAEA), the activity ratio at the moment of administration of the radiopharmaceutical to the patient, should not exceed 0.015%. In Brazil, the control of such parameter is not obliged in official regulations. Thus, the objective of this work is to evaluate the occurrence of 99 Mo in 99m Tc eluates. It was initially optimized a methodology to determine the activity of 99 Mo in eluate samples. Efficiency curves were obtained for a NaI (Tl) 8'' x 4'' scintillation detector installed at the In Vivo Monitoring Laboratory (LABMIV-IRD). The methodology has been validated through the measurement of a 99 Mo standard liquid source calibrated at the National Metrology Laboratory for Ionizing Radiation (LNMRI-IRD). The samples analyzed in this work were gently supplied by 5 Nuclear Medicine Clinics located in the city of Rio de Janeiro. The activities of 99 mTc and 99 Mo in those samples have been measured respectively at the clinics and at the LABMIV. By applying a standardized methodology, the ration between the activities were calculated. The results show that 147 out of 174 samples presented 99 Mo activities above the minimum detectable activity of the technique. On the other hand, only 2 out of 147 samples surpassed the MBT limit suggested by the IAEA and have been detected in samples eluted from generators of 750 mCi. In one of the samples, eluted from a generator of 1000 mCi, the calculated MBT value was very close

A novel electrochemical technique for the production of clinical grade 99mTc using (n, γ)99Mo

International Nuclear Information System (INIS)

Chakravarty, Rubel; Dash, Ashutosh; Venkatesh, Meera

2010-01-01

Introduction: In order to meet the growing demand for 99m Tc and to reduce the reliance on fission-produced 99 Mo, an electrochemical pathway for accessing 99m Tc through the (n, γ) 99 Mo was explored as a back-up measure and to supplement 99m Tc supply for radiopharmaceuticals application. Methods: 99m Tc from an equilibrium mixture of 99 Mo/ 99m Tc was selectively deposited on a platinum cathode in an electrochemical cell by applying optimal voltage and stripped back again into the 0.9% saline solution. The radiochemical and radionuclidic purity of the product were determined using standard techniques. 99m Tc thus obtained was used for labeling standard ligands such as dimercaptosuccinic acid (DMSA) and ethylene dicysteine (EC), to ascertain the usability. Results: Selective deposition of 99m Tc on the platinum electrode was achieved at a potential of 5 V over a period of 1 h in NaOH electrobath. The overall yield of 99m Tc was >90%, with >99.99% radionuclidic purity and >99% radiochemical purity. The performance of the generator remained consistent over a period of 10 days. The compatibility of the product in the preparation of 99m Tc-labeled formulations such as 99m Tc-DMSA and 99m Tc-EC was found to be satisfactory in terms of high labeling yields (>98%). Conclusion: A novel and attractive method has been developed to obtain highly concentrated 99m Tc, without using fission-produced 99 Mo.

Separation of sup(99m)Tc from 99MoO3

International Nuclear Information System (INIS)

Tomicic, M.

1977-07-01

At the present time sup(99m)Tc is widely used in nuclear medicine and its uses are increasing. It can be produced by various methods, and of those most frequently used today two have special features making them particularly applicable to the large-scale production of instant sup(99m)Tc - these are solvent extraction with methyl-ethyl-ketone and the sublimation methods. This report presents a bibliographic review of these methods, their main perfomance parameters, and experience obtained from the development and operation of a sublimation generator. Separation of sup(99m)Tc from irradiated MoO 3 was carried out with high yields (75-95%) after multiple repetition of the separation process with molybdenum trioxide heated for half an hour at a maximum temperature of 850-890 deg C in an air flow. The activity ratio of molybdenum in the separated sup(99m)Tc was of the order of 4 x 10 -5 . (author)

The Supply of Medical Radioisotopes. 2016 Medical Isotope Supply Review: 99Mo/99mTc Market Demand and Production Capacity Projection 2016-2021

International Nuclear Information System (INIS)

Charlton, Kevin; )

2016-03-01

in France permanently shut down operations and late in 2016 one of the largest irradiators, the National Research Universal (NRU) reactor in Canada, will cease routine 99 Mo production, while the associated processing capacity will be maintained and moved to a 'hot standby' mode. New reactor- and non-reactor-based 99 Mo/ 99m Tc projects are expected to be commissioned in various countries. It is important to analyse the overall impact and timing to understand how global production capacity might be affected. This report presents global irradiation and processing capacity under the same three main capacity scenarios as set out in the 2015 report. As in that report, the projected demand and production capacities are presented in six-month intervals. It is intended that this report offers a high added value to the international community and the HLGMR has emphasised the need for future updates on at least an annual basis. The information in this report should be interpreted in terms of projected future trends as opposed to actual forecast values and dates

Influence of the electrolyte in the fixation of {sup 99} Mo in hydroxyapatite as matrix of the {sup 99} Mo/ {sup 99m} Tc generator; Influencia del electrolito en la fijacion de {sup 99} Mo en hidroxiapatita coma matriz del generador {sup 99} Mo/ {sup 99m} Tc

Energy Technology Data Exchange (ETDEWEB)

Vazquez G, S.; Badillo A, V.E. [UAZ, Zacatecas (Mexico); Monroy G, F. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)]. e-mail: s_vazgro@hotmail.com

2005-07-01

The more used isotope at the moment in the services of nuclear medicine in the world is the technetium-99m. The {sup 99m} Tc emitts gamma rays of 141 keV and it semi disintegration period is of six hours, given it short half life, to produce it is necessary to order generators that are systems that allow to separate periodically at the {sup 99m}Tc of the {sup 99} Mo by means of chromatographic techniques. In this work it is sought to evaluate the use of the hydroxyapatite, to separate molybdates {sup 99} MoO{sub 4}{sup 2} of pertechnetates {sup 99m}TcO{sub 4}{sup -} and to be able to determine if it is feasible their use for to build generators of {sup 99m} Tc. With this purpose preliminary tests to know the likeness of the hydroxyapatite for the molybdates in function of the pH value, in different solutions were carried out: one of NaCl 0.9%, NaCl 2% and CaCl{sub 2} 0.01 M. The obtained results in a NaCl 0.9% solution and at to 2% to different pH values of the solution, shows that the fixation of the molybdate ions (MoO{sub 4}{sup -2}) it is worthless to basic pH values of (9-11), as long as in solution of CaCI{sub 2} 0.01 M show a considerable retention of molybdate ions. (Author)

Bioaccumulation of polybrominated diphenyl ethers and decabromodiphenyl ethane in fish from a river system in a highly industrialized area, South China

International Nuclear Information System (INIS)

He, Ming-Jing; Luo, Xiao-Jun; Chen, Man-Ying; Sun, Yu-Xin; Chen, She-Jun; Mai, Bi-Xian

2012-01-01

Polybrominated diphenyl ethers (PBDEs) and decabromodiphenyl ethane (DBDPE) were determined in water, sediment, and three fish species from the Dongjiang River, a highly polluted river by brominated flame retardants in South China due to the intensive industry activities. The stable isotope analysis was used to compare differences between the feeding ecology of the fish species. The bioaccumulations of PBDEs and DBDPE were evaluated by calculation of bioaccumulation factors (BAFs) and biota-sediment accumulation factors (BSAFs). Two potential debromination products of DBDPE were detected in sediment. The occurrence of these two compounds probably ascribed to the thermal degradation during instrumental analysis but degradation in the environment cannot be ruled out. Three fish species showed two quite different PBDE congener profiles. Two carp species were dominated by BDE47 while plecostomus were dominated by both BDE47 and BDE99. The contributions of higher brominated congeners were higher in plecostomus than in two carp species. This different PBDE congener profile can be attributed to the difference in metabolism and feeding habits among fish species. The calculated BAFs for PBDE congeners follow a bioaccumulation model. The BSAFs for all PBDE congeners except for BDE47 and BDE100 were less than unit, implying that bioavailability of PBDEs in sediments is low. Contrary to expectation, the BAFs value of DBDPE was one order of magnitude higher than that of BDE209 in fish, which can partly attributed to the absence of debromination of DBDPE in fish. The calculated BAFs for DBDPE indicated that this compound can significantly accumulate in fish. - Highlights: ►Deca-BDE had gradually substituted by DBDPE in study area. ►Two debrominated products of DBDPE were the result of thermal degradation in instrumental analysis. ►Metabolism and diet were causes for the different PBDE congener profile among fish species. ►Significant bioaccumulation of DBDPE was

Polybrominated diphenyl ethers and their hydroxylated and methoxylated derivatives in seafood obtained from Puget Sound, WA

Energy Technology Data Exchange (ETDEWEB)

Cade, Sara E.; Kuo, Li-Jung; Schultz, Irvin R.

2018-03-07

Synthetic polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental contaminants and known to occur in most food items. Consumer fish products have been identified as having some of the highest PBDE levels found in USA food sources. Natural formation of hydroxylated (OH-) and methoxylated (MeO-) PBDEs are also known to occur in simple marine organisms, which may be bioaccumulated by seafood. In this study, we report findings of an initial survey of PBDE, OH-PBDE and MeO-PBDE content in common seafood items available to residents living in the Puget Sound region of Washington State. Seafood samples were either purchased from local grocery stores or caught off the coast of SE Alaska and in Puget Sound. The edible portions of the seafood were analyzed, which for finfish was white muscle (skinless fillets) and for shellfish, either the entire soft tissue (bivalves) or processed meat (calamari, shrimp and scallops). Results indicated that finfish typically had higher levels of PBDEs compared to shellfish with BDE-47 and BDE-99 as the most common congeners detected. Among shellfish, bivalves (clams and mussels) were notable for having much higher levels of OH- and MeO-PBDEs compared to other types of seafood with 6'-OH-BDE-47 and 2'-MeO-BDE-68 being the more common OH- and MeO- congeners, respectively. Based on our results and recent updates to daily fish consumption rates, estimated intake rates for Washington State residents will be between 34 and 644 ng PBDEs/day, depending on species consumed. For the OH- and MeO- forms, daily exposure is much more variable but typically would range between 15 and 90 ng/day for most seafood types. If shellfish are primarily consumed, OH-PBDE intake could be as high as 350 ng/day. These daily intake rates for PBDEs are higher than most dietary intake rates calculated for populations in other world regions.

32 CFR 99.3 - General definitions.

Science.gov (United States)

2010-07-01

... 32 National Defense 1 2010-07-01 2010-07-01 false General definitions. 99.3 Section 99.3 National... PROCEDURES FOR STATES AND LOCALITIES TO REQUEST INDEMNIFICATION § 99.3 General definitions. For the purposes of §§ 99.1 through 99.9 of this part: Criminal history record information: information collected by...

Measurement and Estimation of the 99Mo Production Yield by 100Mo(n,2n)99Mo

Science.gov (United States)

Minato, Futoshi; Tsukada, Kazuaki; Sato, Nozomi; Watanabe, Satoshi; Saeki, Hideya; Kawabata, Masako; Hashimoto, Shintaro; Nagai, Yasuki

2017-11-01

We, for the first time, measured the yield of 99Mo, the mother nuclide of 99mTc used in nuclear medicine diagnostic procedures, produced by the 100Mo(n,2n)99Mo reaction with accelerator neutrons. The neutrons with a continuous energy spectrum from the thermal energy up to about 40 MeV were provided by the C(d,n) reaction with 40 MeV deuteron beams. It was proved that the 99Mo yield agrees with that estimated by using the latest data on neutrons from the C(d,n) reaction and the evaluated cross section of the 100Mo(n,2n)99Mo reaction given in the Japanese Evaluated Nuclear Data Library. On the basis of the agreement, a systematic calculation was carried out to search for an optimum condition that enables us to produce as much 99Mo as possible with a good 99Mo/100Mo value from an economical point of view. The calculated 99Mo yield from a 150 g 100MoO3 sample indicated that about 30% of the demand for 99Mo in Japan can be met with a single accelerator capable of 40 MeV, 2 mA deuteron beams. Here, by referring to an existing 18F-fluorodeoxyglucose (FDG) distribution system we assumed that 99mTc radiopharmaceuticals formed after separating 99mTc from 99Mo can be delivered to hospitals from a radiopharmaceutical company within 6 h. The elution of 99mTc from 99Mo twice a day would meet about 50% of the demand for 99Mo.

Environmental behavior of technetium-99

International Nuclear Information System (INIS)

Turcotte, M.D.S.

1982-12-01

This report presents a review of the literature on technetium-99. The chemical and physical properties of some technetium compounds are considered, and a discussion of possible source terms is included. Literature on the environmental behavior of technetium is presented, including its behavior in the bodies of animals and humans. The primary sources of Tc-99 in the environment are fallout from atomic detonations and releases from nuclear fuel reprocessing plants. The environmental behavior of technetium-99 has been studied predominantly with respect to movement in soil and accumulation in plants. There is a surprising scarcity of data on behavior of Tc-99 in the atmosphere and in aquatic systems. Additional work needs to be conducted in these two areas to determine behavior and to acquire baseline concentration data. Much of the soil work has produced contradictory results. In-depth studies of holdup mechanisms for Tc-99 in both geological repositories and soil need to be conducted. Since plants represent a potential bioaccumulation of Tc-99, plant uptake studies of Tc-99 under field conditions also need to be done

{sup 201}Tl, {sup 99m}Tc-MIBI, {sup 99m}Tc-tetrofosmin and {sup 99m}Tc-furifosmin: relative retention and clearance kinetics in retrogradely perfused guinea pig hearts

Energy Technology Data Exchange (ETDEWEB)

Schaefer, Wolfgang M.; Moka, Detlef E-mail: detlef.moka@uni-koeln.de; Brockmann, Holger A.; Schomaecker, Klaus; Schicha, Harald

2002-02-01

Myocellular kinetics of {sup 201}Tl, {sup 99m}Tc-MIBI, {sup 99m}Tc-tetrofosmin and {sup 99m}Tc-furifosmin were investigated using retrogradely-perfused guinea-pig hearts. Relative retention decreased in the order {sup 99m}Tc-MIBI {yields}{yields} implies {sup 99m}Tc-tetrofosmin {yields}{yields} implies {sup 99m}Tc-furifosmin. {sup 201}Tl and {sup 99m}Tc-MIBI exhibited bi- (t1,t2), {sup 99m}Tc-tetrofosmin and {sup 99m}Tc-furifosmin triexponential (t1,t2,t3) time-activity-curves. Latest-phase elimination-half-life increased from {sup 201}Tl (t2) {yields}{yields} implies {sup 99m}Tc-MIBI (t2) {yields}{yields} implies {sup 99m}Tc-tetrofosmin (t3) {yields}{yields} implies {sup 99m}Tc-furifosmin (t3), showing a significant increase in deteriorating myocardium for all tracers but {sup 99m}Tc-furifosmin. Delayed elimination in deteriorating myocardium explains at least partly the redistribution phenomenon of {sup 201}Tl, and suggests a similar phenomenon for {sup 99m}Tc-MIBI and {sup 99m}Tc-tetrofosmin.

Determination of 99Mo in 99mTc eluates used in nuclear medicine centers in Rio de Janeiro

International Nuclear Information System (INIS)

Ribeiro, Bianca da S.; Souza, Raphael S.S.; Lucena, Eder A.; Dantas, Ana Leticia A.; Dantas, Bernardo M.

2009-01-01

99m Tc is used in nuclear medicine for image diagnoses with SPECT. It is obtained from the elution of molybdenum-99/technetium-99m ( 99 Mo/ 99m Tc) generators. During the elution, 99 Mo can detach from the column, passing through the filter and mixing in the solution of pertechnetate eluate and becoming a radionuclidic impurity. The presence of molybdenum in the radiopharmaceutical solution imparts an unnecessary radiation dose to the patient, since its half-life is relatively long (66 hours) and it emits beta particles and high-energy photons of (740 keV). A parameter that indicates the quality of the eluates is the radionuclidic purity, the MBT (molybdenum break through), defined as the ratio between 99 Mo and 99m Tc activities in the eluate. The American and the European Pharmacopoeias restrict 99 Mo content to respectively 0.015% and 0.1% activity ratio 99 Mo/ 99m Tc at the time of the administration to the patient. In Brazil, this parameter is not controlled by official regulations. The objective of this work is to determine the presence of 99 Mo in the eluates used in nuclear medicine centers (NMC). The activity measurements of 99 Mo were performed with a NaI(Tl)8''x4'' scintillation detector installed in the IRD whole body counter. The activity of 99m Tc was measured in the NMC where the eluates were collected and, using the established calculations, it was determined the activity ratio 99 Mo/ 99m Tc. The eluate samples were kindly supplied by the participating NMC of Rio de Janeiro. All measurements indicated the presence of 99 Mo. It is concluded that the technique is sensitive to detect 99 Mo in 99m Tc eluates and permits to verify the quality of the generators used in NMC evaluated in this study. (author)

Influence of the electrolyte in the fixation of 99 Mo in hydroxyapatite as matrix of the 99 Mo/ 99m Tc generator

International Nuclear Information System (INIS)

Vazquez G, S.; Badillo A, V.E.; Monroy G, F.

2005-01-01

The more used isotope at the moment in the services of nuclear medicine in the world is the technetium-99m. The 99m Tc emitts gamma rays of 141 keV and it semi disintegration period is of six hours, given it short half life, to produce it is necessary to order generators that are systems that allow to separate periodically at the 99m Tc of the 99 Mo by means of chromatographic techniques. In this work it is sought to evaluate the use of the hydroxyapatite, to separate molybdates 99 MoO 4 2 of pertechnetates 99m TcO 4 - and to be able to determine if it is feasible their use for to build generators of 99m Tc. With this purpose preliminary tests to know the likeness of the hydroxyapatite for the molybdates in function of the pH value, in different solutions were carried out: one of NaCl 0.9%, NaCl 2% and CaCl 2 0.01 M. The obtained results in a NaCl 0.9% solution and at to 2% to different pH values of the solution, shows that the fixation of the molybdate ions (MoO 4 -2 ) it is worthless to basic pH values of (9-11), as long as in solution of CaCI 2 0.01 M show a considerable retention of molybdate ions. (Author)

Utility of the Static-99 and Static-99R With Latino Sex Offenders.

Science.gov (United States)

Leguízamo, Alejandro; Lee, Seung C; Jeglic, Elizabeth L; Calkins, Cynthia

2017-12-01

The predictive validity of the Static-99 measures with ethnic minorities in the United States has only recently been assessed with mixed results. We assessed the predictive validity of the Static-99 and Static-99R with a sample of Latino sex offenders ( N = 483) as well as with two subsamples (U.S.-born, including Puerto Rico, and non-U.S.-born). The overall sexual recidivism rate was very low (1.9%). Both the Static-99 measures were able to predict sexual recidivism for offenders born in the United States and Puerto Rico, but neither was effective in doing so for other Latino immigrants. Calibration analyses ( N = 303) of the Static-99R were consistent with the literature and provided support for the potential use of the measure with Latinos born in the United States and Puerto Rico. These findings and their implications are discussed as they pertain to the assessment of Latino sex offenders.

Photo-production of (99)Mo/(99m)Tc with electron linear accelerator beam.

Science.gov (United States)

Avagyan, R; Avetisyan, A; Kerobyan, I; Dallakyan, R

2014-09-01

We report on the development of a relatively new method for the production of (99)Mo/(99m)Tc. The method involves the irradiation of natural molybdenum using high-intensity bremsstrahlung photons from the electron beam of the LUE50 linear electron accelerator located at the Yerevan Physics Institute (YerPhi). The production method has been developed and shown to be successful. The linear electron accelerator at YerPhi was upgraded to allow for significant increases of the beam intensity and spatial density. The LUE50 was also instrumented by a remote control system for ease of operation. We have developed and tested the (99m)Tc extraction from the irradiation of natural MoO3. This paper reports on the optimal conditions of our method of (99)Mo production. We show the success of this method with the production and separation of the first usable amounts of (99m)Tc. Copyright © 2014 Elsevier Inc. All rights reserved.

22 CFR 99.3 - [Reserved

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false [Reserved] 99.3 Section 99.3 Foreign Relations DEPARTMENT OF STATE LEGAL AND RELATED SERVICES REPORTING ON CONVENTION AND NON-CONVENTION ADOPTIONS OF EMIGRATING CHILDREN § 99.3 [Reserved] ...

The Supply of Medical Radioisotopes. 2015 Medical Isotope Supply Review: 99Mo/99mTc Market Demand and Production Capacity Projection 2015-2020

International Nuclear Information System (INIS)

Charlton, Kevin; )

2015-08-01

-2020 period. In that period, the OSIRIS reactor in France will permanently shut down operations and one of the largest irradiators for medical isotopes, the National Research Universal (NRU) reactor in Canada, will cease routine 99 Mo production and the associated Canadian processing capacity will move offline. In the same period, new reactor- and non-reactor-based 99 Mo/ 99m Tc projects are expected to be commissioned in various countries. It is important to analyse the overall impact and timing of these events to understand how global production capacity might be affected. This report presents global irradiation and processing capacity under three main capacity scenarios. As in the previous 2014 report, the projected demand and production capacity are presented in six-month intervals (January-June and July-December) during the forecast period. The NEA recognises that, as forecast time intervals decrease (e.g. from one year to six months), the timing accuracy of the forecast events may also decrease. The results in this report, however, should be interpreted in terms of the projected future trends as opposed to actual forecast values and dates

Evaluation of 99mTc-Mercaptoacetyltriglycine-Biocytin as a new hepatobiliary imaging agent in mice coinjected with bilirubin

International Nuclear Information System (INIS)

Kim, Meyoung-kon; Seidel, Juergen; Le Nhat; Kim, In-Sook; Yoo, Tae-Moo; Barker, Craig; Kobayashi, Hisataka; Green, Michael V.; Carrasquillo, Jorge A.; Paik, Chang H.

1999-01-01

We evaluated 99m Tc-labeled mercaptoacetyltriglycine ( 99m Tc-MAG3)-biocytin as a hepatobiliary imaging agent in the absence and presence of bilirubin in mice. We then compared its pharmacokinetic parameters; peak liver/heart activity ratio (r max ) and half clearance time (HCT) with those of 99m Tc-labeled diisopropyl-iminodiacetic acid ( 99m Tc-disofenin). Balb/c mice were injected intravenously with hepatobiliary agent ( 99m Tc-MAG3-biocytin or 99m Tc-disofenin) alone or in combination with bilirubin at two doses (7 and 14 mg/kg) dissolved in 5% human serum albumin. Images were acquired every 15 s for 30 min with a gamma-camera equipped with a pinhole collimator. Dynamic images showed rapid hepatic uptake of 99m Tc-MAG3-biocytin, with rapid clearance from the blood and rapid excretion via the biliary system. Its hepatic uptake was not affected by bilirubin coinjection, whereas 99m Tc-disofenin coinjected with bilirubin showed a higher blood background than 99m Tc-disofenin alone. These qualitative findings were reflected in pharmacokinetic parameters, r max and HCT. The r max was obtained from plots of time versus liver/heart activity ratios obtained in equal-area regions of interest over the heart and liver. The HCT was calculated from the hepatic clearance curve from plots of time versus liver activity. 99m Tc-MAG3-biocytin without bilirubin coinjection showed an r max of 8.9±1.3 and an HCT of 399±36 s. These values did not change even when 14 mg/kg of bilirubin were coinjected. By contrast, the parameters for 99m Tc-disofenin with bilirubin were significantly (p max was decreased from 7.9±2.5 to 1.4±0.2 and HCT was increased from 292±32 s to 782±133 s. 99m Tc-MAG3-biocytin hepatobiliary scintigraphy in mice is not affected by bilirubin coinjection, and this hepatobiliary agent appears to offer promise for estimating hepatic function in patients with high bilirubin levels

Technetium-99 ({sup 99}Tc) in annual growth segments of knotted wrack (Ascophyllum nodosum)

Energy Technology Data Exchange (ETDEWEB)

Heldal, Hilde Elise, E-mail: Hilde.Heldal@imr.no [Institute of Marine Research (IMR), PO Box 1870 Nordnes, N-5817 Bergen (Norway); Sjotun, Kjersti, E-mail: Kjersti.Sjotun@bio.uib.no [University of Bergen (UoB), Department of Biology, PO Box 7803, N-5020 Bergen (Norway)

2010-10-15

The distribution of technetium-99 ({sup 99}Tc) in annual growth segments of the brown seaweed Ascophyllum nodosum (Fucales, Phaeophyceae) from the southwestern coast of Norway is examined in samples collected from January to November 2006. A twenty-fold increase in the {sup 99}Tc-concentration from the youngest to the oldest growth segments was found. The concentrations ranged from 42 to 98 Bq/kg dry weight (d.w.) and from 964 to 1000 Bq/kg d.w. in growth segments formed in 2006 and 1996, respectively. In addition, a seasonal variation in the {sup 99}Tc concentration was observed in the actively growing 2006-segments: concentrations decreased from 98 Bq/kg d.w. in April to 54 Bq/kg d.w. in June; there was a further reduction from June to August (42 Bq/kg d.w.); and, finally there was an increase from August to November (93 Bq/kg d.w.). In most of the segments formed between 2000 and 2005, there was a tendency of slightly decreasing {sup 99}Tc-concentrations between June and November but this pattern was not observed for the older growth segments. In order to find an explanation for the non-homogenous distribution of {sup 99}Tc within thalli of A. nodosum, different hypotheses are discussed. Uptake and elimination of {sup 99}Tc appears to be most pronounced in the actively growing segments. To date, such non-homogenous distribution of {sup 99}Tc within thalli of A. nodosum has not been taken into consideration, neither in connection with sample collection nor analysis. This paper shows that special protocols must be followed if A. nodosum is going to be used as a bioindicator for {sup 99}Tc in the marine environment. A sampling strategy is proposed.

Preoperative radiological diagnosis by 99mTc·MIBI-99mTc subtraction scintigraphy for primary hyperparathyroidism

International Nuclear Information System (INIS)

Inouye, Takahiro; Tomita, Toshiki; Shinden, Seiichi; Takagi, Hitoshi; Kano, Shigeru.

1996-01-01

Preoperative radiological diagnosis constitutes the most important factor for the surgical treatment of hyperparathyroidism. In this regard, MRI is useful for detecting the abnormal parathyroid, but it is often difficult to localize it using MRI only. It is thus necessary to combine this procedure with excellent subtraction scintigraphy. We performed both 201 Tl- 99m Tc and 99m Tc·MIBI- 99m Tc subtraction scintigraphy in seven patients with primary hyperparathyroidism and compared them the radiological results. Five patients presented parathyroid adenomas and the rest hypertrophy of the parathyroid. We could detect the abnormal parathyroid in four patients (57.1%) by 201 Tl- 99m Tc subtraction scintigraphy and in six patients (85.7%) by 99m Tc·MIBI- 99m Tc subtraction scintigraphy. We therefore believe that 99m Tc·MIBI- 99m Tc subtraction scintigraphy will become an essential examination for primary hyperparathyroidism rather than the presently employed 201 Tl- 99m Tc subtraction scintigraphy. (author)

Problems in clinical practice of domestic supply of 99Mo/99mTc. The direction and problem of stable supply chain of 99Mo in Japan

International Nuclear Information System (INIS)

Inoue, Tomio

2013-01-01

The shortage of supply of 99 Mo caused by trouble of old nuclear reactors in Canada and Europe caused international problem in the field of nuclear medicine, which has not been completely resolved yet. Because all of 99 Mo/ 99m Tc generator in Japan has been imported, Japan Atomic Energy Commission (JAEC) suggested the necessity of establishment of stable supply chain of 99 Mo ( 99 Mo/ 99m Tc generator). According this suggestion, an ad hoc committee appointed to consider the stable supply chain, which consisted of persons concerned with industry, academic society, Japan Isotope Association, Ministry of Education, Culture, Sports, Science, and Technology-Japan (MEXT), Ministry of Health, Labour and Welfare (MHLW), Japan Atomic Energy Agency (JAEA), National Institute of Radiological Science (NIRS) et al., evaluated and compared several ways of production and purification of 99 Mo from the view point of technological maturity, regulation compatibility, economic suitability, and stability for supply. In this review, the summary of the committee report is introduced. For short term strategy, we need to keep the variable import routes for 99 Mo. As a mid-term goal, we need to establish the supply chain inside Japan as a conclusion of the committee report but it seems to be not easy for utility of nuclear reactor after nuclear accident of Fukushima Daiichi Nuclear Power Plant. The development of the method for 99 Mo/ 99m Tc production using accelerator is also expected for the establishment of stable supply chain. (author)

14 CFR 99.12 - [Reserved

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false [Reserved] 99.12 Section 99.12 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR TRAFFIC AND GENERAL OPERATING RULES SECURITY CONTROL OF AIR TRAFFIC General § 99.12 [Reserved] ...

Dexamethasone and azathioprine promote cytoskeletal changes and affect mesenchymal stem cell migratory behavior.

Directory of Open Access Journals (Sweden)

Natália Schneider

Full Text Available Glucocorticoids and immunosuppressive drugs are commonly used to treat inflammatory disorders, such as inflammatory bowel disease (IBD, and despite a few improvements, the remission of IBD is still difficult to maintain. Due to their immunomodulatory properties, mesenchymal stem cells (MSCs have emerged as regulators of the immune response, and their viability and activation of their migratory properties are essential for successful cell therapy. However, little is known about the effects of immunosuppressant drugs used in IBD treatment on MSC behavior. The aim of this study was to evaluate MSC viability, nuclear morphometry, cell polarity, F-actin and focal adhesion kinase (FAK distribution, and cell migratory properties in the presence of the immunosuppressive drugs azathioprine (AZA and dexamethasone (DEX. After an initial characterization, MSCs were treated with DEX (10 μM or AZA (1 μM for 24 hrs or 7 days. Neither drug had an effect on cell viability or nuclear morphometry. However, AZA treatment induced a more elongated cell shape, while DEX was associated with a more rounded cell shape (P < 0.05 with a higher presence of ventral actin stress fibers (P < 0.05 and a decrease in protrusion stability. After 7 days of treatment, AZA improved the cell spatial trajectory (ST and increased the migration speed (24.35%, P < 0.05, n = 4, while DEX impaired ST and migration speed after 24 hrs and 7 days of treatment (-28.69% and -25.37%, respectively; P < 0.05, n = 4. In conclusion, our data suggest that these immunosuppressive drugs each affect MSC morphology and migratory capacity differently, possibly impacting the success of cell therapy.

The risk analysis used to manufacture 99Mo/99mTc generators

International Nuclear Information System (INIS)

Fano Machín, Yoiz; Alberti Ramírez, Alejandro; Gamboa Marrero, Regla; Suárez Beyríes, Karina; Cruz Morales, Amed

2016-01-01

In this work the steps to be followed for the risk analysis in the process of production of 99 Mo / 99m Tc generators in CENTIS, using the methodology of analysis of modes and effects of failures are collected. The analysis of the type and probability of occurrence of the failures in the process, as well as the impact on the quality of the same and the probability of detection of such failures, were used for the use of techniques used in quality assurance such as: storm Ideas and cause-effect diagram. Scales were established for the determination of severity, probability of occurrence, probability of detection and calculation of the number of risk probabilities. The guidelines were laid down for the future application of this technique, which will establish a decision-making process regarding the risks associated with the production process of 99 Mo / 99m Tc generators. (author)

Integrin β1 regulates leiomyoma cytoskeletal integrity and growth

Science.gov (United States)

Malik, Minnie; Segars, James; Catherino, William H.

2014-01-01

Uterine leiomyomas are characterized by an excessive extracellular matrix, increased mechanical stress, and increased active RhoA. Previously, we observed that mechanical signaling was attenuated in leiomyoma, but the mechanisms responsible remain unclear. Integrins, especially integrin β1, are transmembrane adhesion receptors that couple extracellular matrix stresses to the intracellular cytoskeleton to influence cell proliferation and differentiation. Here we characterized integrin and laminin to signaling in leiomyoma cells. We observed a 2.25 ± 0.32 fold increased expression of integrin β1 in leiomyoma cells, compared to myometrial cells. Antibody-mediated inhibition of integrin β1 led to significant growth inhibition in leiomyoma cells and a loss of cytoskeletal integrity. Specifically, polymerization of actin filaments and formation of focal adhesions were reduced by inhibition of integrin p1. Inhibition of integrin β1 in leiomyoma cells led to 0.81 ± 0.02 fold decrease in active RhoA, and resembled levels found in serum-starved cells. Likewise, inhibition of integrin β1 was accompanied by a decrease in phospho-ERK. Compared to myometrial cells, leiomyoma cells demonstrated increased expression of integrin α6 subunit to laminin receptor (1.91 ± 0.11 fold), and increased expression of laminin 5α (1.52±0.02), laminin 5β (3.06±0.92), and laminin 5γ (1.66 ± 0.06). Of note, leiomyoma cells grown on laminin matrix appear to realign themselves. Taken together, the findings reveal that the attenuated mechanical signaling in leiomyoma cells is accompanied by an increased expression and a dependence on integrin β1 signaling in leiomyoma cells, compared to myometrial cells. PMID:23023061

Quinolinic acid neurotoxicity: Differential roles of astrocytes and microglia via FGF-2-mediated signaling in redox-linked cytoskeletal changes.

Science.gov (United States)

Pierozan, Paula; Biasibetti, Helena; Schmitz, Felipe; Ávila, Helena; Parisi, Mariana M; Barbe-Tuana, Florencia; Wyse, Angela T S; Pessoa-Pureur, Regina

2016-12-01

QUIN is a glutamate agonist playing a role in the misregulation of the cytoskeleton, which is associated with neurodegeneration in rats. In this study, we focused on microglial activation, FGF2/Erk signaling, gap junctions (GJs), inflammatory parameters and redox imbalance acting on cytoskeletal dynamics of the in QUIN-treated neural cells of rat striatum. FGF-2/Erk signaling was not altered in QUIN-treated primary astrocytes or neurons, however cytoskeleton was disrupted. In co-cultured astrocytes and neurons, QUIN-activated FGF2/Erk signaling prevented the cytoskeleton from remodeling. In mixed cultures (astrocyte, neuron, microglia), QUIN-induced FGF-2 increased level failed to activate Erk and promoted cytoskeletal destabilization. The effects of QUIN in mixed cultures involved redox imbalance upstream of Erk activation. Decreased connexin 43 (Cx43) immunocontent and functional GJs, was also coincident with disruption of the cytoskeleton in primary astrocytes and mixed cultures. We postulate that in interacting astrocytes and neurons the cytoskeleton is preserved against the insult of QUIN by activation of FGF-2/Erk signaling and proper cell-cell interaction through GJs. In mixed cultures, the FGF-2/Erk signaling is blocked by the redox imbalance associated with microglial activation and disturbed cell communication, disrupting the cytoskeleton. Thus, QUIN signal activates differential mechanisms that could stabilize or destabilize the cytoskeleton of striatal astrocytes and neurons in culture, and glial cells play a pivotal role in these responses preserving or disrupting a combination of signaling pathways and cell-cell interactions. Taken together, our findings shed light into the complex role of the active interaction of astrocytes, neurons and microglia in the neurotoxicity of QUIN. Copyright © 2016 Elsevier B.V. All rights reserved.

Preparation of Human Serum Albumin Macroaggregated (MAA) labelled with 99mTc via Ligand Exchange

International Nuclear Information System (INIS)

El-Mohty, A.A.; El-Ghany, E.A.; Amin, A.A.; El-Koaly, M.T.; Raieh, M.

2000-01-01

An alternative method for the preparation of human serum albumin macroaggregated (MAA) labelled with 99m Tc for lung scanning is described. The method is based on the use of stannous methylene diphosphonate (Sn-MDP) as a reducing agent. The may be also increase the number of binding sites in the MAA. The different parameters affecting the labelling yield and in-vitro stability of 99m Tc-MAA have been studied in order to determine the optimum conditions for labelling macroaggregated with 99m Tc. A high labelling yield (98.9%) was achieved and more than 98% of 99m Tc-MAA coated with Sn-MDP. The determined lung uptake in mice was found to be ≥ 90% which better than the reported data. A particular procedure compared to the existing reported procedures, which is recommended for the preparation of Sn-MDP coated MAA labelled with 99m Tc for lung perfusion imaging

Location of and post-mortem changes in some cytoskeletal proteins in pork and cod muscle

DEFF Research Database (Denmark)

Morrison, E.H.; Bremner, Allan; Purslow, P.P.

2000-01-01

The cytoskeletal proteins actin, nebulin, spectrin, desmin, vinculin and talin were labelled immunohistochemically in sections of muscle from commercially available pigs and cod (Gadus morhua) taken pre-rigor and from samples stored for several days. Actin, nebulin and spectrin gave similar...... labelling patterns in both pork and cod muscle which remained the same in stored samples. Desmin was intensely labelled at the cell boundaries and within the body of the cells in both pork and cod in the initial and the stored samples. Vinculin was readily labelled in pork muscle but showed only diffuse...... labelling in fish. Labelling for talin in pork muscle was intense at the sarcolemma but was not present in samples stored for 4 days. In contrast, the label for talin was concentrated at the myotendinous junction of the cod muscle throughout the storage period. These are the first reports of the detection...

Preparation of hypoxic imaging agents 99Tcm-MNLS and 99Tcm-MLS and their biodistribution in mice

International Nuclear Information System (INIS)

Zha Zhihao; Wang Jianjun; Zhu Lin

2009-01-01

To develop 99 Tc m labeled hypoxic agents,two phosphate-based chelating agents were coupled to metronidazole, 2- (2-methyl-5-nitro-1H-imidazol-1-yl) ethyl dihydrogen phosphate (MNLS) and its analog 2- (2-methyl-1H-imidazol-1-yl) ethyl dihydrogen phosphate (MLS) were synthesized based on the mechanism of prodrug. Labeling yield of these 99 Tc m complexes were more than 90% as proved by TLC. Paper electrophoresis showed that these complexes were neutral. Biodistribution of these complexes in tumor-bearing mice showed that the uptake of 99 Tc m -MNLS (120 min, 2.99 ± 0.25 ID%/g) in tumor was higher than that of 99 Tc m -HL91 (120 min, 0.93 ± 0.13 ID%/g) and 99 Tc m -MLS (120 min, 1.61 ± 0.13 ID%/g), and the uptake ratio of tumor to muscle and tumor to liver of 99 Tc m -MNLS (120 min, 5.90, 1.03) were higher than that of 99 Tc m -HL91 (120 min, 3.59, 0.17) and 99 Tc m -MLS (120 min, 5.40, 0.13). The higher tumor uptake for 99 Tc m -MNLS than 99 Tc m -MLS suggested that nitroimidazole was a key group for tumor accumulation. 99 Tc m -MNLS had higher tumor uptake and lower liver uptake, which had the potential for tumor imaging and was worth of further vestigation. (authors)

14 CFR 99.41 - General.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false General. 99.41 Section 99.41 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR TRAFFIC AND GENERAL OPERATING RULES SECURITY CONTROL OF AIR TRAFFIC Designated Air Defense Identification Zones § 99...

14 CFR 99.3 - Definitions.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Definitions. 99.3 Section 99.3 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR TRAFFIC AND GENERAL OPERATING RULES SECURITY CONTROL OF AIR TRAFFIC General § 99.3 Definitions. Aeronautical facility...

A simple and sensitive separation technique of 99Mo and 99mTc from their equilibrium mixture

International Nuclear Information System (INIS)

Swadesh Mandal; Ajoy Mandal

2014-01-01

The present work describes a simple and inexpensive separation method of 99 Mo from the equilibrium mixture. The liquid-liquid extraction technique has been employed to separate 99 Mo and 99m Tc using triisooctylamine (TIOA). The 99 Mo and 99m Tc were quantitatively separated out in 2 M TIOA with tripled distilled water; 99m Tc was back extracted from TIOA organic phase to aqueous phase by 0.1 M DTPA. The species information or indirect speciation of molybdenum was also established by the extraction profile of the molybdenum. (author)

The separation of sup(99m)Tc from 99Mo through an aluminium oxide chromatographic columm

International Nuclear Information System (INIS)

Imoto, S.T.

1980-01-01

The separation of sup(99m)Tc from 99 Mo using the chromatographic method is studied. Alumina is used as adsorbent. The pH values for adsorption of carrier-free 99 Mo on columns filled with ordinary alumina and with that thermically treated at 1000 0 C for five hours, and the separation conditions of sup(99m)Tc using physiologic solution as eluent are determined. The sup(99m)Tc separation yields of both columns are compared and the quality of the products obtained by successive elutions for 10 days is analyzed. (Author) [pt

Concentration of polybrominated diphenyl ethers (PBDEs) in sediment cores of Sundarban mangrove wetland, northeastern part of Bay of Bengal (India)

International Nuclear Information System (INIS)

Binelli, Andrea; Sarkar, Santosh Kumar; Chatterjee, Mousumi; Riva, Consuelo; Parolini, Marco; Bhattacharya, Bhaskar deb; Bhattacharya, Asok Kumar; Satpathy, Kamala Kanta

2007-01-01

The paper presents the first comprehensive survey of congener profiles (12 congeners) of polybrominated diphenyl ethers (PBDEs) in core sediment samples ( 12 PBDE values ranging from 0.08 to 29.03 ng g -1 , reflecting moderate to low contamination closely in conformity to other Asian aquatic environments. The general order of decreasing congener contribution to the total load was: BDE 47 > 99 > 100 > 154, similar to the distribution pattern worldwide. Although tetrabromodiphenyl ether BDE 47 was found in all samples followed by hexabromodiphenyl ether BDE-154, they were not necessarily the dominant congeners. No uniform temporal trend on PBDE levels was recorded probably due to particular hydrological characteristics of the wetland and/on non-homologous inputs from point sources (untreated municipal wastewater and local industries, electronic wastes from the dump sites, etc.) of these compounds. Because of the propensity of PBDEs to accumulate in various compartments of wildlife and human food webs, evaluation of biological tissues should be undertaken as a high priority

45 CFR 99.25 - Evidence.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Evidence. 99.25 Section 99.25 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROCEDURE FOR HEARINGS FOR THE CHILD CARE AND DEVELOPMENT FUND Hearing Procedures § 99.25 Evidence. (a) Testimony. Testimony shall be given orally under...

22 CFR 99.1 - Definitions.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Definitions. 99.1 Section 99.1 Foreign Relations DEPARTMENT OF STATE LEGAL AND RELATED SERVICES REPORTING ON CONVENTION AND NON-CONVENTION ADOPTIONS OF EMIGRATING CHILDREN § 99.1 Definitions. As used in this part, the term: (a) Convention means...

45 CFR 99.23 - Discovery.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Discovery. 99.23 Section 99.23 Public Welfare... DEVELOPMENT FUND Hearing Procedures § 99.23 Discovery. The Department, the Lead Agency, and any individuals or groups recognized as parties shall have the right to conduct discovery (including depositions) against...

{sup 99m}Tc generator preparation using (n, {gamma}){sup 99}Mo produced ex-natural molybdenum

Energy Technology Data Exchange (ETDEWEB)

Le, So Van [Nuclear Research Institute, Dalat (Viet Nam)

2003-03-01

Theoretical assessment on the chromatographic {sup 99m}Tc generator preparation using (n, {gamma}) {sup 99}Mo produced ex-natural molybdenum was carried out. The relationship between the neutron flux for MoO{sub 3} target activation, Mo-content or Mo adsorption capacity of column packing material, {sup 99m}Tc pertechnetate concentration and/or {sup 99m}Tc radioactivity of eluate was established. The reasonably lower limit of neutron flux of reactor and Molybdenum content of column packing material were found out to estimate the production of portable chromatographic generators available for nuclear medicine application. The concentration of {sup 99m}Tc pertechnetate eluate of low {sup 99m}Tc concentration using the column elution technique was also evaluate theoretically and conducted successfully in practice. Three options of {sup 99m}Tc generator using Titanium-Molybdate, Zirconium-Molybdate and Zirconium Oxide as generator column-packing materials were prepared and successfully put into use in nuclear medicine application. (author)

Photolytic debromination pathway of polybrominated diphenyl ethers in hexane by sunlight

International Nuclear Information System (INIS)

Wei, Hua; Zou, Yonghong; Li, An; Christensen, Erik R.; Rockne, Karl J.

2013-01-01

The objective of this work is to identify the photolytic debromination pathways of polybrominated diphenyl ethers (PBDEs). Thirteen PBDEs (BDEs 209, 208, 207, 206, 196, 183, 154, 153, 100, 99, 85, 47 and 28) in hexane were individually exposed to sunlight for up to 64 h. A total of 180 PBDEs were screened and 74 BDE debromination products were detected. The disappearance rate constant increased exponentially with increasing number of bromines. While no evident difference in debromination preference among ortho, meta and para bromines was found for heavier congeners, the vulnerability rank order was meta ≥ ortho > para for the lighter congeners (≤8 Br). The total molar mass of PBDEs continuously decreased during sunlight exposure, indicating PBDEs were transformed to non-PBDE compounds. A stochastic least squares debromination pathway model was developed to simulate the reactions and determine the yields to extend the results beyond the experimental observations. -- Highlights: ► 74 PBDEs are identified as the products of debromination via photolysis. ► Debromination is more likely at meta than para positions for PBDEs with ≤8 bromines. ► The stochastic least squares model results agree with and expand the experimental observations. ► Mass imbalance indicates a significant loss of PBDE mass during sunlight exposure. -- The PBDE debromination products and pathways identified in this work will assist in future studies on their environmental fate

Gridded field observations of polybrominated diphenyl ethers in soils of North China.