Ameliorative influence of Urtica dioica L against cisplatin-induced toxicity in mice bearing Ehrlich ascites carcinoma.

PubMed

Özkol, Halil; Musa, Davut; Tuluce, Yasin; Koyuncu, Ismail

2012-07-01

Cisplatin (CP) is a widely used cytotoxic agent against cancer, and high doses of CP have been known to cause nephrotoxicity and hepatotoxicity. Some reports claim that antioxidants can reduce CP-induced toxicity. This study investigated the hepatoprotective, nephroprotective, and antioxidant activity of Urtica dioica L methanolic extract (UDME) against CP toxicity in Erhlich ascites tumor (EAT)-bearing mice. Levels of serum hepatic enzymes, renal function markers, and oxidant/antioxidant parameters of liver tissue were measured. Mice were inoculated with EAT on day 0 and treated with nothing else for 24 hours. After a single dose of CP administration on day 1, the extract was given at the doses of 50, 100, 200, and 400 mg/kg body weight daily during 6 days. Almost all doses of UDME performed a significant (P < 0.05) preventive role against CP toxicity by decreasing aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, blood urea nitrogen, creatinine, lipid peroxidation, protein oxidation levels, and myeloperoxidase activity, as well as increasing reduced glutathione content, superoxide dismutase, catalase, glutathione S-transferase, and glutathione peroxidase activities. This suggests that UDME has a protective capacity and antioxidant activity against CP toxicity in EAT-bearing mice, probably by promoting antioxidative defense systems.

Diffusivity of hydrogen in iron-bearing olivine at 3 GPa

NASA Astrophysics Data System (ADS)

Demouchy, Sylvie; Thoraval, Catherine; Bolfan-Casanova, Nathalie; Manthilake, Geeth

2016-11-01

The kinetics of hydrogenation of dry iron-bearing olivine single crystals was determined by performing hydration experiments under hydrothermal conditions at high pressure. The experiments were performed in a multi-anvil press at 3 GPa, for a temperature range between 900 and 1200 °C and for various durations. The oxygen fugacity was buffered along Ni-NiO joint. Polarized Fourier transform infrared spectroscopy and recent empirical calibration were used to quantify the hydroxyl distributions in the samples along crystallographic axes after the experiments. The chemical diffusion coefficients are similar (barely slower) than in olivine hydrated at lower pressure (0.2 and 0.3 GPa) for the same diffusion mechanism. Under the given experimental conditions, the anisotropy of diffusion is the same as for proton-vacancy mechanism, with diffusion along the [0 0 1] axis faster than along the [1 0 0]. However, the anisotropy at 3 GPa is weaker compared to measurements at lower pressures and the analysis of concentration profiles using 3D models shows that an isotropic solution could also be relevant. Fits of the diffusion data to an Arrhenius law yield activation energies for the slightly faster [0 0 1] axis of the crystallographic axes around 198 ± 5 kJ mol-1, a value only slightly lower than the results from previous experimental studies for natural iron-bearing olivine hydrogenated at lower confining pressure. At 3 GPa, hydrogenation can be well approximated by a single mechanism controlled by coupled diffusion of protons and octahedral vacancies (di- and tri-valent ions). The diffusion rates are fast enough to alter hydrogen concentration within olivine in xenoliths ascending from the mantle or experiencing hydrogen-rich metasomatism events, but too slow to permit complete homogenization of hydrogen in olivine-rich rocks at kilometer scale in less than one My.

An immunohistochemical study of retinol-binding protein (RBP) in livers of free-living polar bears (Ursus maritimus) from east Greenland.

PubMed

Heier, Annabelle; Sonne, Christian; Gröne, Andrea; Leifsson, Pall S; Dietz, Rune; Born, Erik W; Bacciarini, Luca N

2005-09-01

From 1999 to 2002 samples from 114 free-ranging polar bears (Ursus maritimus) were collected in the municipality of Scoresby Sound, East Greenland, to detect levels of organochlorines and potential histopathologic changes. Livers of 16 female polar bears from this group were evaluated histologically and analyzed for hepatic retinol-binding protein by immunohistochemistry. Retinol-binding protein is the main transport protein for retinol, an important vitamin A metabolite in the polar bear. Only mild pathologic changes were noted on histologic evaluation of the livers. Small lymphocytic or lymphohistiocytic infiltrates were present in all the livers. Small lipid granulomas, mild periportal fibrosis, and bile duct proliferation were found in several cases. Immunohistochemistry for retinol-binding protein of hepatic tissue from free-ranging polar bears showed no distinct difference in staining intensity by a number of criteria: age, season (fasting and nonfasting), or lactation status. The staining was diffuse to finely stippled in the cytoplasm and showed very little variation among the animals. Because of the lack of macroscopic changes and the absence of severe histologic liver lesions, these polar bears were assumed to be healthy. The diffuse cytoplasmic retinol-binding protein staining in hepatocytes of free-ranging polar bears varies markedly from the prominent granular, less intense staining of captive polar bears investigated previously.

Cross-Diffusion Induced Turing Instability and Amplitude Equation for a Toxic-Phytoplankton-Zooplankton Model with Nonmonotonic Functional Response

NASA Astrophysics Data System (ADS)

Han, Renji; Dai, Binxiang

2017-06-01

The spatiotemporal pattern induced by cross-diffusion of a toxic-phytoplankton-zooplankton model with nonmonotonic functional response is investigated in this paper. The linear stability analysis shows that cross-diffusion is the key mechanism for the formation of spatial patterns. By taking cross-diffusion rate as bifurcation parameter, we derive amplitude equations near the Turing bifurcation point for the excited modes in the framework of a weakly nonlinear theory, and the stability analysis of the amplitude equations interprets the structural transitions and stability of various forms of Turing patterns. Furthermore, we illustrate the theoretical results via numerical simulations. It is shown that the spatiotemporal distribution of the plankton is homogeneous in the absence of cross-diffusion. However, when the cross-diffusivity is greater than the critical value, the spatiotemporal distribution of all the plankton species becomes inhomogeneous in spaces and results in different kinds of patterns: spot, stripe, and the mixture of spot and stripe patterns depending on the cross-diffusivity. Simultaneously, the impact of toxin-producing rate of toxic-phytoplankton (TPP) species and natural death rate of zooplankton species on pattern selection is also explored.

NASA/MSFC multilayer diffusion models and computer program for operational prediction of toxic fuel hazards

NASA Technical Reports Server (NTRS)

Dumbauld, R. K.; Bjorklund, J. R.; Bowers, J. F.

1973-01-01

The NASA/MSFC multilayer diffusion models are discribed which are used in applying meteorological information to the estimation of toxic fuel hazards resulting from the launch of rocket vehicle and from accidental cold spills and leaks of toxic fuels. Background information, definitions of terms, description of the multilayer concept are presented along with formulas for determining the buoyant rise of hot exhaust clouds or plumes from conflagrations, and descriptions of the multilayer diffusion models. A brief description of the computer program is given, and sample problems and their solutions are included. Derivations of the cloud rise formulas, users instructions, and computer program output lists are also included.

Kurarinol induces hepatocellular carcinoma cell apoptosis through suppressing cellular signal transducer and activator of transcription 3 signaling

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

Shu, Guangwen; Yang, Jing; Zhao, Wenhao

Kurarinol is a flavonoid isolated from roots of the medical plant Sophora flavescens. However, its cytotoxic activity against hepatocellular carcinoma (HCC) cells and toxic effects on mammalians remain largely unexplored. Here, the pro-apoptotic activities of kurarinol on HCC cells and its toxic impacts on tumor-bearing mice were evaluated. The molecular mechanisms underlying kurarinol-induced HCC cell apoptosis were also investigated. We found that kurarinol dose-dependently provoked HepG2, Huh-7 and H22 HCC cell apoptosis. In addition, kurarinol gave rise to a considerable decrease in the transcriptional activity of signal transducer and activator of transcription 3 (STAT3) in HCC cells. Suppression of STAT3more » signaling is involved in kurarinol-induced HCC cell apoptosis. In vivo studies showed that kurarinol injection substantially induced transplanted H22 cell apoptosis with low toxic impacts on tumor-bearing mice. Similarly, the transcriptional activity of STAT3 in transplanted tumor tissues was significantly suppressed after kurarinol treatment. Collectively, our current research demonstrated that kurarinol has the capacity of inducing HCC cell apoptosis both in vitro and in vivo with undetectable toxic impacts on the host. Suppressing STAT3 signaling is implicated in kurarinol-mediated HCC cell apoptosis. - Highlights: • Kurarinol induces hepatocellular carcinoma (HCC) cell apoptosis. • Kurarinol induces HCC cell apoptosis via inhibiting STAT3. • Kurarinol exhibits low toxic effects on tumor-bearing animals.« less

Marine Biotoxins: Occurrence, Toxicity, and Detection Methods

NASA Astrophysics Data System (ADS)

Asakawa, M.

2017-04-01

This review summarizes the role of marine organisms as vectors of marine biotoxins, and discusses the need for surveillance to protect public health and ensure the quality of seafood. I Paralytic shellfish poison (PSP) and PSP-bearing organisms-PSP is produced by toxic dinoflagellates species belonging to the genera Alexandrium, Gymnodinium, and Pyrodinium. Traditionally, PSP monitoring programs have only considered filter-feeding molluscs that concentrate these toxic algae, however, increasing attention is now being paid to higher-order predators that carry PSP, such as carnivorous gastropods and crustaceans. II. Tetrodotoxin (TTX) and TTX-bearing organisms - TTX is the most common natural marine toxin that causes food poisonings in Japan, and poses a serious public health risk. TTX was long believed to be present only in pufferfish. However, TTX was detected in the eggs of California newt Taricha torosa in 1964, and since then it has been detected in a wide variety of species belonging to several different phyla. In this study, the main toxic components in the highly toxic ribbon worm Cephalothrix simula and the greater blue-ringed octopus Hapalochlaena lunulata from Japan were purified and analysed.

A double medium model for diffusion in fluid-bearing rock

NASA Astrophysics Data System (ADS)

Wang, H. F.

1993-09-01

The concept of a double porosity medium to model fluid flow in fractured rock has been applied to model diffusion in rock containing a small amount of a continuous fluid phase that surrounds small volume elements of the solid matrix. The model quantifies the relative role of diffusion in the fluid and solid phases of the rock. The fluid is the fast diffusion path, but the solid contains the volumetrically significant amount of the diffusing species. The double medium model consists of two coupled differential equations. One equation is the diffusion equation for the fluid concentration; it contains a source term for change in the average concentration of the diffusing species in the solid matrix. The second equation represents the assumption that the change in average concentration in a solid element is proportional to the difference between the average concentration in the solid and the concentration in the fluid times the solid-fluid partition coefficient. The double medium model is shown to apply to laboratory data on iron diffusion in fluid-bearing dunite and to measured oxygen isotope ratios at marble-metagranite contacts. In both examples, concentration profiles are calculated for diffusion taking place at constant temperature, where a boundary value changes suddenly and is subsequently held constant. Knowledge of solid diffusivities can set a lower bound to the length of time over which diffusion occurs, but only the product of effective fluid diffusivity and time is constrained for times longer than the characteristic solid diffusion time. The double medium results approach a local, grain-scale equilibrium model for times that are large relative to the time constant for solid diffusion.

Wollastonite Carbonation in Water-Bearing Supercritical CO2: Effects of Particle Size.

PubMed

Min, Yujia; Li, Qingyun; Voltolini, Marco; Kneafsey, Timothy; Jun, Young-Shin

2017-11-07

The performance of geologic CO 2 sequestration (GCS) can be affected by CO 2 mineralization and changes in the permeability of geologic formations resulting from interactions between water-bearing supercritical CO 2 (scCO 2 ) and silicates in reservoir rocks. However, without an understanding of the size effects, the findings in previous studies using nanometer- or micrometer-size particles cannot be applied to the bulk rock in field sites. In this study, we report the effects of particle sizes on the carbonation of wollastonite (CaSiO 3 ) at 60 °C and 100 bar in water-bearing scCO 2 . After normalization by the surface area, the thickness of the reacted wollastonite layer on the surfaces was independent of particle sizes. After 20 h, the reaction was not controlled by the kinetics of surface reactions but by the diffusion of water-bearing scCO 2 across the product layer on wollastonite surfaces. Among the products of reaction, amorphous silica, rather than calcite, covered the wollastonite surface and acted as a diffusion barrier to water-bearing scCO 2 . The product layer was not highly porous, with a specific surface area 10 times smaller than that of the altered amorphous silica formed at the wollastonite surface in aqueous solution. These findings can help us evaluate the impacts of mineral carbonation in water-bearing scCO 2 .

Divalent Naphthalene Diimide Ligands Display High Selectivity for the Human Telomeric G‐quadruplex in K+ Buffer

PubMed Central

Street, Steven T. G.; Chin, Donovan N.; Hollingworth, Gregory J.; Berry, Monica

2017-01-01

Abstract Selective G‐quadruplex ligands offer great promise for the development of anti‐cancer therapies. A novel series of divalent cationic naphthalene diimide ligands that selectively bind to the hybrid form of the human telomeric G‐quadruplex in K+ buffer are described herein. We demonstrate that an imidazolium‐bearing mannoside‐conjugate is the most selective ligand to date for this quadruplex against several other quadruplex and duplex structures. We also show that a similarly selective methylpiperazine‐bearing ligand was more toxic to HeLa cancer cells than doxorubicin, whilst exhibiting three times less toxicity towards fetal lung fibroblasts WI‐38. PMID:28257554

Roxarsone and its metabolites in chicken manure significantly enhance the uptake of As species by vegetables.

PubMed

Huang, Lianxi; Yao, Lixian; He, Zhaohuan; Zhou, Changmin; Li, Guoliang; Yang, Baomei; Deng, Xiancai

2014-04-01

Roxarsone is an organoarsenic feed additive which can be finally degraded to other higher toxic metabolites after excreted by animal. In this work, the uptake of As species by vegetables treated with chicken manure bearing roxarsone and its metabolites was investigated. It was showed that more than 96% of roxarsone added in chicken feed was degraded and converted to arsenite, monomethylarsonic acid, dimethylarsinic acid, arsenate, 4-hydroxyphenylarsonic acid and other unknown As species. Arsenite and arsenate could be found in roots of vegetables but only arsenite transported up to shoots. Chicken manure bearing roxarsone and its metabolites increased 33-175% of arsenite and 28% ∼ seven times of arsenate in vegetable roots, 68-175% of arsenite in edible vegetable shoots. Arsenite, the most toxic As form, was the major extractable As species in vegetables accounted for 79-98%. The results reflected that toxic element As could be absorbed by vegetables via the way: roxarsone in feed → animal → animal manure → soil → crop and the uptake of As species would be enhanced by using chicken manure bearing roxarsone and its metabolites as organic fertilizer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Portsmouth Gaseous Diffusion Plant expansion: final environmental statement. Volume 2. Appendices. [Appendices only

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

Liverman, James L.

Volume 2 is comprised of appendices: Portsmouth Gaseous Diffusion Plant Existing Facilities; Ecology; Civic Involvement; Social Analysis; Population Projections; Toxicity of Air Pollutants to Biota at Portsmouth Gaseous Diffusion Plant; and Assessment of Noise Effects of an Add-On to the Portsmouth Gaseous Diffusion Plant. (LK)

Preliminary data of the antipancreatic tumor efficacy and toxicity of long-circulating and pH-sensitive liposomes containing cisplatin.

PubMed

Carlesso, Fernanda N; Araújo, Raquel S; Fuscaldi, Leonardo L; Mendes Miranda, Sued E; Rubello, Domenico; Teixeira, Cláudia S; Dos Reis, Diego C; Leite, Elaine A; Silveira, Josianne N; Fernandes, Simone O A; Cassali, Geovanni D; de Oliveira, Mônica C; Colletti, Patrick M; de Barros, André L B; Cardoso, Valbert N

2016-07-01

Pancreatic cancer is the fourth most common cause of cancer-related death in the USA. This is mainly because of the chemoresistance of this type of tumor; thus, the development of novel therapeutic modalities is needed. Long-circulating and pH-sensitive liposomes containing cisplatin (SpHL-CDDP) were administered systemically into pancreatic tumor-bearing mice for a period of 14 days. The antitumor efficacy and toxicity of this new treatment method on the basis of cisplatin-loaded liposomes was compared with the classical free-CDDP method. Tc-HYNIC-βAla-bombesin(7-14) tumor uptake and histopathologic findings were used to monitor and compare the two treatment modalities. The antitumor activity of SpHL-CDDP treatment was shown by (a) decrease in tumor volume, (b) development of tumor necrotic areas, and (c) decrease in Tc-HYNIC-βAla-bombesin(7-14) tumor uptake. Toxicity was evaluated by the development of inflammation and necrotic areas in the kidneys, liver, spleen, and intestine: toxic effects were greater with free-CDDP than SpHL-CDDP. SpHL-CDDP showed significant antitumor activity in pancreatic cancer-bearing mice, with lower toxicity in comparison with free-CDDP.

Some basic mathematical methods of diffusion theory. [emphasis on atmospheric applications

NASA Technical Reports Server (NTRS)

Giere, A. C.

1977-01-01

An introductory treatment of the fundamentals of diffusion theory is presented, starting with molecular diffusion and leading up to the statistical methods of turbulent diffusion. A multilayer diffusion model, designed to permit concentration and dosage calculations downwind of toxic clouds from rocket vehicles, is described. The concepts and equations of diffusion are developed on an elementary level, with emphasis on atmospheric applications.

Modeling the Role of Incisures in Vertebrate Phototransduction

PubMed Central

Caruso, Giovanni; Bisegna, Paolo; Shen, Lixin; Andreucci, Daniele; Hamm, Heidi E.; DiBenedetto, Emmanuele

2006-01-01

Phototransduction is mediated by a G-protein-coupled receptor-mediated cascade, activated by light and localized to rod outer segment (ROS) disk membranes, which, in turn, drives a diffusion process of the second messengers cGMP and Ca2+ in the ROS cytosol. This process is hindered by disks—which, however, bear physical cracks, known as incisures, believed to favor the longitudinal diffusion of cGMP and Ca2+. This article is aimed at highlighting the biophysical functional role and significance of incisures, and their effect on the local and global response of the photocurrent. Previous work on this topic regarded the ROS as well stirred in the radial variables, lumped the diffusion mechanism on the longitudinal axis of the ROS, and replaced the cytosolic diffusion coefficients by effective ones, accounting for incisures through their total patent area only. The fully spatially resolved model recently published by our group is a natural tool to take into account other significant details of incisures, including their geometry and distribution. Using mathematical theories of homogenization and concentrated capacity, it is shown here that the complex diffusion process undergone by the second messengers cGMP and Ca2+ in the ROS bearing incisures can be modeled by a family of two-dimensional diffusion processes on the ROS cross sections, glued together by other two-dimensional diffusion processes, accounting for diffusion in the ROS outer shell and in the bladelike regions comprised by the stack of incisures. Based on this mathematical model, a code has been written, capable of incorporating an arbitrary number of incisures and activation sites, with any given arbitrary distribution within the ROS. The code is aimed at being an operational tool to perform numerical experiments of phototransduction, in rods with incisures of different geometry and structure, under a wide spectrum of operating conditions. The simulation results show that incisures have a dual biophysical function. On the one hand, since incisures line up from disk to disk, they create vertical cytoplasmic channels crossing the disks, thus facilitating diffusion of second messengers; on the other hand, at least in those species bearing multiple incisures, they divide the disks into lobes like the petals of a flower, thus confining the diffusion of activated phosphodiesterase and localizing the photon response. Accordingly, not only the total area of incisures, but their geometrical shape and distribution as well, significantly influence the global photoresponse. PMID:16714347

Cellular Inclusion Bodies of Mutant Huntingtin Exon 1 Obscure Small Fibrillar Aggregate Species

PubMed Central

Sahl, Steffen J.; Weiss, Lucien E.; Duim, Whitney C.; Frydman, Judith; Moerner, W. E.

2012-01-01

The identities of toxic aggregate species in Huntington's disease pathogenesis remain ambiguous. While polyQ-expanded huntingtin (Htt) is known to accumulate in compact inclusion bodies inside neurons, this is widely thought to be a protective coping response that sequesters misfolded conformations or aggregated states of the mutated protein. To define the spatial distributions of fluorescently-labeled Htt-exon1 species in the cell model PC12m, we employed highly sensitive single-molecule super-resolution fluorescence imaging. In addition to inclusion bodies and the diffuse pool of monomers and oligomers, fibrillar aggregates ~100 nm in diameter and up to ~1–2 µm in length were observed for pathogenic polyQ tracts (46 and 97 repeats) after targeted photo-bleaching of the inclusion bodies. These short structures bear a striking resemblance to fibers described in vitro. Definition of the diverse Htt structures in cells will provide an avenue to link the impact of therapeutic agents to aggregate populations and morphologies. PMID:23193437

Acute encephalopathy with biphasic seizures and late reduced diffusion associated with staphylococcal toxic shock syndrome caused by burns.

PubMed

Yokochi, Takaoki; Sakanishi, Shinpei; Ishidou, Yuuki; Kawano, Go; Matsuishi, Toyojiro; Akita, Yukihiro; Obu, Keizo

2016-10-01

We report a case of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) associated with toxic shock syndrome caused by burns. A one-year-old girl was admitted to our hospital for treatment of severe burns. On day 3, she exhibited a fever, generalized rash and multiple organ failure. She was diagnosed with toxic shock syndrome after burns. She had seizures with fever twice on the same day, followed by secondary seizures on day 8 and transient deterioration of the gross motor functions involved in sitting alone and rolling over. On day 9, MRI diffusion-weighted images showed bright tree appearance (BTA). We conclude that she developed AESD. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

The impact of cemented layers and hardpans on oxygen diffusivity in mining waste heaps: a field study of the Halsbrücke lead-zinc mine tailings (Germany).

PubMed

Kohfahl, Claus; Graupner, Torsten; Fetzer, Christian; Pekdeger, Asaf

2010-11-01

This article reports fibre-optic oxygen measurements on a reactive mine waste heap located in the polymetallic sulphide mine district of Freiberg in south-eastern Germany. The heaped material consists of sulphide-bearing tailings from a processing plant of a lead-zinc mine. Mine waste material was deposited in the water phase after separation of mining ores in a flotation process. The tailing impoundment is partly covered with coarse sand and topsoil. Oxygen profiles were monitored during one year at eleven locations showing different physical and mineralogical compositions. At each location a borehole was drilled where the optic sensors were installed at 2-5 different depths. After installation the oxygen profiles were monitored seven times during one year from 2006-2007 and three to five oxygen profiles at each location were obtained. Oxygen measurements were accompanied by physical, chemical and mineralogical data of the tailing material. Additionally, a detailed mineralogical profile was analysed at a location representative for the central part of the heap, where the cemented layers show lateral continuity. Results showed that cemented layers have a significant influence on natural attenuation of the toxic As and Pb species owing to their capacity of water retention. The measured oxygen profiles are controlled by the zone of active pyrite weathering as well as by the higher water content in the cemented layers which reduces gaseous atmospheric oxygen supply. In contrast, gypsum bearing hardpans detected at three other locations have no detectable influence on oxygen profiles. Furthermore, the grain size distribution was proved to have a major effect on oxygen diffusivity due to its control on the water saturation. Temporal changes of the oxygen profiles were only observed at locations with coarse sediment material indicating also an important advective part of gas flux. Copyright © 2010 Elsevier B.V. All rights reserved.

Case Study: From Gummy Bears to Celery Stalks--Diffusion and Osmosis

ERIC Educational Resources Information Center

Bonney, Kevin M.

2014-01-01

This article describes an interrupted case study that intersperses information about diffusion and osmosis with content review and knowledge application questions, as well as a simple experiment that can be conducted without the use of a laboratory. The case study was developed for use in an introductory undergraduate biology course. The case…

[Prevention of postoperative hypothyroidism in surgical treatment of diffuse toxic goiter].

PubMed

Aristarkhov, V G; Kirillov, Iu B; Panteleev, I V

2001-01-01

Experience of treatment of more than 1000 patients with diffuse toxic goiter (DTG) is presented. Complex of measures performed before and after operation for reduction of hypothyroidism rate is developed. Histology examination during operation permits to determine volume of residual thyroid tissue. Local laserotherapy improves long-term results of surgical treatment. Rate of postoperative hypothyroidism in patients with DTG has decreased from 43.6 to 3.3%.

Dermal Sensitization Potential of Triethyleneglycol Dinitrate (TEGDN) in Guinea Pigs

DTIC Science & Technology

1989-01-01

mutagenicity assay, acute oral toxicity tests in rats and mice, acute dermal toxicity in rabbits, dermal and ocular irritation studies in rabbits, and...conditions: 85E0102 had diffuse tracheitis, mild endocarditis , mild hepatitis, and diffuse pigment granules in the small intestine; 85E0103 had mild...severe ulceration progressing to necrosis. Sensitization is manifested as indirect inflammation mediated by components of the immune system in

Antitumoral activity and toxicity of PEG-coated and PEG-folate-coated pH-sensitive liposomes containing ¹⁵⁹Gd-DTPA-BMA in Ehrlich tumor bearing mice.

PubMed

Soares, Daniel Crístian Ferreira; Cardoso, Valbert Nascimento; de Barros, André Luís Branco; de Souza, Cristina Maria; Cassali, Geovanni Dantas; de Oliveira, Mônica Cristina; Ramaldes, Gilson Andrade

2012-01-23

In the present study, PEG-coated pH-sensitive and PEG-folate-coated pH-sensitive liposomes containing the ¹⁵⁹Gd-DTPA-BMA were prepared and radiolabeled through neutron activation technique, aiming to study the in vivo antitumoral activity and toxicity on mice bearing a previously-developed solid Ehrlich tumor. The treatment efficacy was verified through tumoral volume increase and histomorphometry studies. The toxicity of formulations was investigated through animal weight variations, as well as hematological and biochemical tests. The results showed that after 31 days of treatment, animals treated with radioactive formulations had a lower increase in tumor volume and a significantly higher percentage of necrosis compared with controls revealed by histomorphometry studies. Furthermore, mice treated with radioactive formulations exhibited lower weight gain without significant hematological or biochemical changes, except for toxicity to hepatocytes which requires more detailed studies. From the results obtained to date, we believe that the radioactive formulations can be considered potential therapeutic agents for cancer. Copyright © 2011 Elsevier B.V. All rights reserved.

Hepatoprotective effect of acetone semicarbazone on Ehrlich ascites carcinoma induced carcinogenesis in experimental mice

PubMed Central

Islam, Farhadul; Ali, Shaikh Mohummad Mohsin; Khanam, Jahan Ara

2013-01-01

Objective To determine the hepatoprotective effect of acetone semicarbazone (ASC) in vivo in normal and Ehrlich ascites carcinoma (EAC) bearing male Swiss albino mice. Methods Drug-induced changes in biochemical and behavioral parameters at dose of 2.0 mg/kg body weight for 14 d and nullifying the toxicity induced by EAC cells were studied. The histopathology studies of the protective effects of ASC on vital organs were also assessed. Results The administration of ASC made insignificant changes in body weight and behavioral (salivation, diarrhea, muscular numbness) changes during treatment period due to minor toxicity were minimized after the treatment in normal mice. The biochemical parameters, including serum glutamate pyruvate transaminase, glutamate oxaloactate transaminase, alkaline phosphatase, serum glucose, cholesterol, urea, triglyceride and billirubin changed modestly in normal mice receiving ASC. Though the treatment continued, these values gradually decreased to normal level after the treatment. In EAC bearing mice, the toxic effects due to EAC cells in all cases were nullified by treatment with the ASC. Significant abnormalities were not detected in histology of the various organs of the normal mice treated with ASC. Conclusions ASC can, therefore, be considered safe in formulating novel anticancer drug, as it exhibits strong protective effect against EAC cell bearing mice. PMID:23593588

Optical (diffuse reflectance) and Mossbauer spectroscopic study of nontronite and related Fe-bearing smectites

USGS Publications Warehouse

Sherman, David M.; Vergo, N.

1988-01-01

Near-ultraviolet to near-infrared optical (diffuse reflectance) spectra of several nontronites and related Fe-bearing smectites [(Fe2+,Fe3+)-bearing saponite and (Fe2+,Fe3+)-bearing montmorillonite] are presented and interpreted. Mossbauer spectra at 298 K are also presented to help interpret the optical spectra. The optical spectra of nontronites are dominated by the ligand field transitions of Fe3+ in octahedral coordination sites. In addition to the ligand field transitions of single Fe3+ cations, a broad absorption band centered near 22000 cm-1 is observed that may be due to the simultaneous excitation of two Fe3+ cations to the 4T1g (4G) state. Alternatively, this band may represent excitations to the 2A2g and 2T1g ligand field states. For most samples, the amount of tetrahedrally coordinated Fe3+ was below that detectable by Mossbauer spectroscopy (1-3% of total Fe). However, the optical spectra of all of the nontronites show an absorption band near 23000 cm-1. This band is assigned to the 6A1 ??? 4E,4A1 transition of tetrahedrally coordinated Fe3+. The optical spectra of mixed-valence Fe-bearing smectites show a broad absorption band at 14000-15000 cm-1 owing to Fe2+ ??? Fe3+ charge transfer. -from Authors

Cancer-selective, single agent chemoradiosensitising gold nanoparticles

PubMed Central

Grellet, Sophie; Tzelepi, Konstantina; Roskamp, Meike; Williams, Phil; Sharif, Aquila; Slade-Carter, Richard; Goldie, Peter; Whilde, Nicky; Śmiałek, Małgorzata A.; Mason, Nigel J.

2017-01-01

Two nanometre gold nanoparticles (AuNPs), bearing sugar moieties and/or thiol-polyethylene glycol-amine (PEG-amine), were synthesised and evaluated for their in vitro toxicity and ability to radiosensitise cells with 220 kV and 6 MV X-rays, using four cell lines representing normal and cancerous skin and breast tissues. Acute 3 h exposure of cells to AuNPs, bearing PEG-amine only or a 50:50 ratio of alpha-galactose derivative and PEG-amine resulted in selective uptake and toxicity towards cancer cells at unprecedentedly low nanomolar concentrations. Chemotoxicity was prevented by co-administration of N-acetyl cysteine antioxidant, or partially prevented by the caspase inhibitor Z-VAD-FMK. In addition to their intrinsic cancer-selective chemotoxicity, these AuNPs acted as radiosensitisers in combination with 220 kV or 6 MV X-rays. The ability of AuNPs bearing simple ligands to act as cancer-selective chemoradiosensitisers at low concentrations is a novel discovery that holds great promise in developing low-cost cancer nanotherapeutics. PMID:28700660

Parametric studies with an atmospheric diffusion model that assesses toxic fuel hazards due to the ground clouds generated by rocket launches

NASA Technical Reports Server (NTRS)

Stewart, R. B.; Grose, W. L.

1975-01-01

Parametric studies were made with a multilayer atmospheric diffusion model to place quantitative limits on the uncertainty of predicting ground-level toxic rocket-fuel concentrations. Exhaust distributions in the ground cloud, cloud stabilized geometry, atmospheric coefficients, the effects of exhaust plume afterburning of carbon monoxide CO, assumed surface mixing-layer division in the model, and model sensitivity to different meteorological regimes were studied. Large-scale differences in ground-level predictions are quantitatively described. Cloud alongwind growth for several meteorological conditions is shown to be in error because of incorrect application of previous diffusion theory. In addition, rocket-plume calculations indicate that almost all of the rocket-motor carbon monoxide is afterburned to carbon dioxide CO2, thus reducing toxic hazards due to CO. The afterburning is also shown to have a significant effect on cloud stabilization height and on ground-level concentrations of exhaust products.

Minuteman III Motor-Generator Bearing Grease Replacement

DTIC Science & Technology

2013-07-01

Biodegradation is a natural process caused by the action of microorganisms in the presence of oxygen, nitrogen, phosphorous, and trace minerals. Organic... biodegradable are considered less toxic and more environmentally friendly. Currently, this technology has been mandated in order to reduce the ...AFB2 grease and Capella WF-68 oil currently used in the MINUTEMAN III Motor-generator (M-G) Bearing Systems. Due to the unavailability

Grizzly bear hair reveals toxic exposure to mercury through salmon consumption.

PubMed

Noël, Marie; Spence, Jody; Harris, Kate A; Robbins, Charles T; Fortin, Jennifer K; Ross, Peter S; Christensen, Jennie R

2014-07-01

Mercury obtained from the diet accumulates in mammalian hair as it grows thus preserving a record of mercury intake over the growth period of a given hair segment. We adapted a microanalysis approach, using laser ablation inductively coupled plasma mass spectrometry, to characterize temporal changes in mercury exposure and uptake in wild and captive grizzly bears. Captive grizzlies fed diets containing known and varied amounts of mercury provided data to allow prediction of Hg ingestion rates in wild bears. Here, we show, for the first time, that 70% of the coastal grizzly bears sampled had Hg levels exceeding the neurochemical effect level proposed for polar bears. In a context where the international community is taking global actions to reduce Hg emissions through the "Minamata Convention on Mercury", our study provides valuable information on the exposure to mercury of these grizzly bears already under many threats.

Indium-bearing sulfides from the Hämmerlein skarn deposit, Erzgebirge, Germany: evidence for late-stage diffusion of indium into sphalerite

NASA Astrophysics Data System (ADS)

Bauer, Matthias E.; Seifert, Thomas; Burisch, Mathias; Krause, Joachim; Richter, Nancy; Gutzmer, Jens

2017-12-01

At the Hämmerlein skarn deposit, located in the western Erzgebirge (Germany), a major cassiterite-dominated Sn mineralization stage is spatially associated with a younger Zn-Cu-In sulfide mineralization stage. In this contribution, we provide the first detailed description of the Zn-Cu-In sulfide mineralization stage, based on field geological observations combined with detailed petrographic studies and electron probe microanalysis data. Indium-rich sulfide mineralization occurs as irregular, semi-massive lenses or as infill of short, discontinuous veinlets that crosscut the cassiterite-bearing skarn assemblage. Indium- and Cu-rich sphalerite and roquesite are found to be closely associated with In-bearing chalcopyrite. The highest In concentrations in sphalerite occur at the rims and along cracks of sphalerite grains. The distribution resembles diffusion profiles, suggesting that the In enrichment is due to an hydrothermal overprint that postdates the initial formation of both sphalerite and chalcopyrite. Textural relations illustrate that the diffusion fronts in sphalerite grains are thicker where they are in contact to anhedral masses of hematite and magnetite. Our observations suggest that In enrichment in sphalerite at the Hämmerlein skarn deposit is due to the decomposition of In-bearing chalcopyrite. The resultant release of Fe led to the formation of hematite and magnetite, whereas Cu and In were incorporated into sphalerite along grain boundaries and micro fractures. Incorporation into the sphalerite lattice took place by coupled substitution of Cu+ + In3+ ↔ 2Zn2+, suggesting that the concurrent availability of Cu and In may be an essential factor to enrich In in sphalerite in hydrothermal ore-forming environments.

Are liver and renal lesions in East Greenland polar bears (Ursus maritimus) associated with high mercury levels?

PubMed

Sonne, Christian; Dietz, Rune; Leifsson, Pall S; Asmund, Gert; Born, Erik W; Kirkegaard, Maja

2007-04-17

In the Arctic, polar bears (Ursus maritimus) bio-accumulate mercury as they prey on polluted ringed seals (Phoca hispida) and bearded seals (Erignathus barbatus). Studies have shown that polar bears from East Greenland are among the most mercury polluted species in the Arctic. It is unknown whether these levels are toxic to liver and kidney tissue. We investigated the histopathological impact from anthropogenic long-range transported mercury on East Greenland polar bear liver (n = 59) and kidney (n = 57) tissues. Liver mercury levels ranged from 1.1-35.6 microg/g wet weight and renal levels ranged from 1-50 microg/g wet weight, of which 2 liver values and 9 kidney values were above known toxic threshold level of 30 microg/g wet weight in terrestrial mammals. Evaluated from age-correcting ANCOVA analyses, liver mercury levels were significantly higher in individuals with visible Ito cells (p < 0.02) and a similar trend was found for lipid granulomas (p = 0.07). Liver mercury levels were significantly lower in individuals with portal bile duct proliferation/fibrosis (p = 0.007) and a similar trend was found for proximal convoluted tubular hyalinisation in renal tissue (p = 0.07). Based on these relationships and the nature of the chronic inflammation we conclude that the lesions were likely a result of recurrent infections and ageing but that long-term exposure to mercury could not be excluded as a co-factor. The information is important as it is likely that tropospheric mercury depletion events will continue to increase the concentrations of this toxic heavy metal in the Sub Arctic and Arctic marine food webs.

Tetrodotoxin – Distribution and Accumulation in Aquatic Organisms, and Cases of Human Intoxication

PubMed Central

Noguchi, Tamao; Arakawa, Osamu

2008-01-01

Many pufferfish of the family Tetraodontidae possess a potent neurotoxin, tetrodotoxin (TTX). In marine pufferfish species, toxicity is generally high in the liver and ovary, whereas in brackish water and freshwater species, toxicity is higher in the skin. In 1964, the toxin of the California newt was identified as TTX as well, and since then TTX has been detected in a variety of other organisms. TTX is produced primarily by marine bacteria, and pufferfish accumulate TTX via the food chain that begins with these bacteria. Consequently, pufferfish become non-toxic when they are fed TTX-free diets in an environment in which the invasion of TTX-bearing organisms is completely shut off. Although some researchers claim that the TTX of amphibians is endogenous, we believe that it also has an exogenous origin, i.e., from organisms consumed as food. TTX-bearing animals are equipped with a high tolerance to TTX, and thus retain or accumulate TTX possibly as a biologic defense substance. There have been many cases of human intoxication due to the ingestion of TTX-bearing pufferfish, mainly in Japan, China, and Taiwan, and several victims have died. Several cases of TTX intoxication due to the ingestion of small gastropods, including some lethal cases, were recently reported in China and Taiwan, revealing a serious public health issue. PMID:18728726

Atomistic Molecular Dynamics Simulations of Charged Latex Particle Surfaces in Aqueous Solution.

PubMed

Li, Zifeng; Van Dyk, Antony K; Fitzwater, Susan J; Fichthorn, Kristen A; Milner, Scott T

2016-01-19

Charged particles in aqueous suspension form an electrical double layer at their surfaces, which plays a key role in suspension properties. For example, binder particles in latex paint remain suspended in the can because of repulsive forces between overlapping double layers. Existing models of the double layer assume sharp interfaces bearing fixed uniform charge, and so cannot describe aqueous binder particle surfaces, which are soft and diffuse, and bear mobile charge from ionic surfactants as well as grafted multivalent oligomers. To treat this industrially important system, we use atomistic molecular dynamics simulations to investigate a structurally realistic model of commercial binder particle surfaces, informed by extensive characterization of particle synthesis and surface properties. We determine the interfacial profiles of polymer, water, bound and free ions, from which the charge density and electrostatic potential can be calculated. We extend the traditional definitions of the inner and outer Helmholtz planes to our diffuse interfaces. Beyond the Stern layer, the simulated electrostatic potential is well described by the Poisson-Boltzmann equation. The potential at the outer Helmholtz plane compares well to the experimental zeta potential. We compare particle surfaces bearing two types of charge groups, ionic surfactant and multivalent oligomers, with and without added salt. Although the bare charge density of a surface bearing multivalent oligomers is much higher than that of a surfactant-bearing surface at realistic coverage, greater counterion condensation leads to similar zeta potentials for the two systems.

Hotfire testing of a SSME HPOTP with an annular hydrostatic bearing

NASA Technical Reports Server (NTRS)

Nolan, Steven A.; Hibbs, Robert I.; Genge, Gary G.

1993-01-01

A new fluid film bearing package has been tested in the SSME High Pressure Oxygen Turbopump (HPOTP). This fluid film element functions as both the pump end bearing and the preburner pump rear wear ring seal. Most important, it replaces a duplex ball bearing package which has been the primary life limiting component in the turbopump. The design and predicted performance of the turbopump are reviewed. Results are presented for measured pump and bearing performance. The most significant results were obtained from proximity probes located in the bearing bore which revealed large subsynchronous precession at 10 percent of shaft speed during engine start which subsided prior to mainstage power levels and reappeared during engine shutdown at equivalent power levels below 65 percent of nominal. This phenomenon has been attributed to rotating stall in the diffuser. The proximity probes also revealed the location of the bearing in the bore for different operating speeds. Pump vibration characteristics were improved as compared to pumps tested with ball bearings. After seven starts and more than 700 seconds of testing, the pump showed no signs of performance degradation.

Experimental validation of a model for diffusion-controlled absorption of organic compounds in the trachea

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

Gerde, P.; Muggenburg, B.A.; Thornton-Manning, J.R.

1995-12-01

Most chemically induced lung cancer originates in the epithelial cells in the airways. Common conceptions are that chemicals deposited on the airway surface are rapidly absorbed through mucous membranes, limited primarily by the rate of blood perfusion in the mucosa. It is also commonly thought that for chemicals to induce toxicity at the site of entry, they must be either rapidly reactive, readily metabolizable, or especially toxic to the tissues at the site of entry. For highly lipophilic toxicants, there is a third option. Our mathematical model predicts that as lipophilicity increases, chemicals partition more readily into the cellular lipidmore » membranes and diffuse more slowly through the tissues. Therefore, absorption of very lipophilic compounds will be almost entirely limited by the rate of diffusion through the epithelium rather than by perfusion of the capillary bed in the subepithelium. We have reported on a preliminary model for absorption through mucous membranes of any substance with a lipid/aqueous partition coefficient larger than one. The purpose of this work was to experimentally validate the model in Beagle dogs. This validated model on toxicant absorption in the airway mucosa will improve risk assessment of inhaled« less

Sorption and modeling of mass transfer of toxic chemical vapors in activated-carbon fiber-cloth adsorbers

USGS Publications Warehouse

Lordgooei, M.; Sagen, J.; Rood, M.J.; Rostam-Abadi, M.

1998-01-01

A new activated-carbon fiber-cloth (ACFC) adsorber coupled with an electrothermal regenerator and a cryogenic condenser was designed and developed to efficiently capture and recover toxic chemical vapors (TCVs) from simulated industrial gas streams. The system was characterized for adsorption by ACFC, electrothermal desorption, and cryogenic condensation to separate acetone and methyl ethyl ketone from gas streams. Adsorption dynamics are numerically modeled to predict system characteristics during scale-up and optimization of the process in the future. The model requires diffusivities of TCVs into an activated-carbon fiber (ACF) as an input. Effective diffusivities of TCVs into ACFs were modeled as a function of temperature, concentration, and pore size distribution. Effective diffusivities for acetone at 65 ??C and 30-60 ppmv were measured using a chromatography method. The energy factor for surface diffusion was determined from comparison between the experimental and modeled effective diffusivities. The modeled effective diffusivities were used in a dispersive computational model to predict mass transfer zones of TCVs in fixed beds of ACFC under realistic conditions for industrial applications.

14 CFR Appendix I to Part 417 - Methodologies for Toxic Release Hazard Analysis and Operational Procedures

Code of Federal Regulations, 2010 CFR

2010-01-01

... physics on the transport and diffusion of each toxicant. (5) Meteorological conditions at the time of launch. (6) Population density, location, susceptibility (health categories) and sheltering for all..., or for use in any real-time physics models used to ensure compliance with the toxic flight commit...

ERG and other discriminators between advanced hydroxychloroquine retinopathy and retinitis pigmentosa.

PubMed

Nair, Archana A; Marmor, Michael F

2017-06-01

To study whether the ERG and other clinical findings help to distinguish between advanced hydroxychloroquine (HCQ) retinopathy and pericentral or diffuse retinitis pigmentosa (RP) with similar fundus appearance. We conducted a retrospective analysis of patients with advanced HCQ retinopathy (n = 11), pericentral RP (n = 8) and diffuse RP (n = 8). Pericentral RP was defined as having limited fundus damage and relatively normal flicker ERG time-to-peak. Diffuse RP had typical loss of the rod ERG and flicker timing delay. All patients showed reduced amplitude of the ISCEV responses in the full-field electroretinogram (ERG). Aspects of history, visual field results, fundus appearance, fundus autofluorescence and ocular coherence tomography were also compared. Relative to pericentral RP, patients with HCQ toxicity showed delayed flicker ERG time-to-peak and lower ERG amplitudes, particularly combined rod-cone responses. Relative to diffuse RP, most HCQ toxicity patients had some preserved rod ERG response, and there was no obvious predilection for rod over cone damage. In addition, patients with HCQ toxicity usually lacked markers of long-standing degeneration such as bone spicule figures or severe loss of peripheral field. History of familial disease and long-standing night blindness were specific to RP. While the early signs of HCQ damage are typically regional in the posterior pole, advanced disease is characteristically diffuse (unlike pericentral RP). This is appropriate for a systemic toxin, as is the finding that rods and cones were both affected in the ERG to a similar degree (unlike genetic rod-cone dystrophies). For patients with severe HCQ exposure and some of our discriminatory findings, and no family history or prior night blindness, HCQ toxicity is a sufficient diagnosis without invoking a second rare disease (Occam's razor).

Two reference time scales for studying the dynamic cavitation of liquid films

NASA Technical Reports Server (NTRS)

Sun, D. C.; Brewe, D. E.

1992-01-01

Two formulas, one for the characteristic time of filling a void with the vapor of the surrounding liquid, and one of filling the void by diffusion of the dissolved gas in the liquid, are derived. By comparing these time scales with that of the dynamic operation of oil film bearings, it is concluded that the evaporation process is usually fast enough to fill the cavitation bubble with oil vapor; whereas the diffusion process is much too slow for the dissolved air to liberate itself and enter the cavitation bubble. These results imply that the formation of a two phase fluid in dynamically loaded bearings, as often reported in the literature, is caused by air entrainment. They further indicate a way to simplify the treatment of the dynamic problem of bubble evolution.

Experimental Evidence for Fast Lithium Diffusion and Isotope Fractionation in Water-bearing Rhyolitic Melts at Magmatic Conditions

NASA Astrophysics Data System (ADS)

Cichy, S. B.; Till, C. B.; Roggensack, K.; Hervig, R. L.; Clarke, A. B.

2015-12-01

The aim of this work is to extend the existing database of experimentally-determined lithium diffusion coefficients to more natural cases of water-bearing melts at the pressure-temperature range of the upper crust. In particular, we are investigating Li intra-melt and melt-vapor diffusion and Li isotope fractionation, which have the potential to record short-lived magmatic processes (seconds to hours) in the shallow crust, especially during decompression-induced magma degassing. Hydrated intra-melt Li diffusion-couple experiments on Los Posos rhyolite glass [1] were performed in a piston cylinder at 300 MPa and 1050 °C. The polished interfaces between the diffusion couples were marked by addition of Pt powder for post-run detection. Secondary ion mass spectrometry analyses indicate that lithium diffuses extremely fast in the presence of water. Re-equilibration of a hydrated ~2.5 mm long diffusion-couple experiment was observed during the heating period from room temperature to the final temperature of 1050 °C at a rate of ~32 °C/min. Fractionation of ~40‰ δ7Li was also detected in this zero-time experiment. The 0.5h and 3h runs show progressively higher degrees of re-equilibration, while the isotope fractionation becomes imperceptible. Li contamination was observed in some experiments when flakes filed off Pt tubing were used to mark the diffusion couple boundary, while the use of high purity Pt powder produced better results and allowed easier detection of the diffusion-couple boundary. The preliminary lithium isotope fractionation results (δ7Li vs. distance) support findings from [2] that 6Li diffuses substantially faster than 7Li. Further experimental sets are in progress, including lower run temperatures (e.g. 900 °C), faster heating procedure (~100 °C/min), shorter run durations and the extension to mafic systems. [1] Stanton (1990) Ph.D. thesis, Arizona State Univ., [2] Richter et al. (2003) GCA 67, 3905-3923.

A quantum diffusion law

NASA Astrophysics Data System (ADS)

Satpathi, Urbashi; Sinha, Supurna; Sorkin, Rafael D.

2017-12-01

We analyse diffusion at low temperature by bringing the fluctuation-dissipation theorem (FDT) to bear on a physically natural, viscous response-function R(t) . The resulting diffusion-law exhibits several distinct regimes of time and temperature, each with its own characteristic rate of spreading. As with earlier analyses, we find logarithmic spreading in the quantum regime, indicating that this behavior is robust. A consistent R(t) must satisfy the key physical requirements of Wightman positivity and passivity, and we prove that ours does so. We also prove in general that these two conditions are equivalent when the FDT holds. Given current technology, our diffusion law can be tested in a laboratory with ultra cold atoms.

(2S)-2-(3-(1-Carboxy-5-(4-211At-Astatobenzamido)Pentyl)Ureido)-Pentanedioic Acid for PSMA-Targeted α-Particle Radiopharmaceutical Therapy

PubMed Central

Kiess, Ana P.; Minn, Il; Vaidyanathan, Ganesan; Hobbs, Robert F.; Josefsson, Anders; Shen, Colette; Brummet, Mary; Chen, Ying; Choi, Jaeyeon; Koumarianou, Eftychia; Baidoo, Kwamena; Brechbiel, Martin W.; Mease, Ronnie C.; Sgouros, George; Zalutsky, Michael R.

2016-01-01

Alpha-particle emitters have a high linear energy transfer and short range, offering the potential for treating micrometastases while sparing normal tissues. We developed a urea-based, 211At-labeled small molecule targeting prostate-specific membrane antigen (PSMA) for the treatment of micrometastases due to prostate cancer (PC). Methods: PSMA-targeted (2S)-2-(3-(1-carboxy-5-(4-211At-astatobenzamido)pentyl)ureido)-pentanedioic acid (211At-6) was synthesized. Cellular uptake and clonogenic survival were tested in PSMA-positive (PSMA+) PC3 PIP and PSMA-negative (PSMA−) PC3 flu human PC cells after 211At-6 treatment. The antitumor efficacy of 211At-6 was evaluated in mice bearing PSMA+ PC3 PIP and PSMA– PC3 flu flank xenografts at a 740-kBq dose and in mice bearing PSMA+, luciferase-expressing PC3-ML micrometastases. Biodistribution was determined in mice bearing PSMA+ PC3 PIP and PSMA– PC3 flu flank xenografts. Suborgan distribution was evaluated using α-camera images, and microscale dosimetry was modeled. Long-term toxicity was assessed in mice for 12 mo. Results: 211At-6 treatment resulted in PSMA-specific cellular uptake and decreased clonogenic survival in PSMA+ PC3 PIP cells and caused significant tumor growth delay in PSMA+ PC3 PIP flank tumors. Significantly improved survival was achieved in the newly developed PSMA+ micrometastatic PC model. Biodistribution showed uptake of 211At-6 in PSMA+ PC3 PIP tumors and in kidneys. Microscale kidney dosimetry based on α-camera images and a nephron model revealed hot spots in the proximal renal tubules. Long-term toxicity studies confirmed that the dose-limiting toxicity was late radiation nephropathy. Conclusion: PSMA-targeted 211At-6 α-particle radiotherapy yielded significantly improved survival in mice bearing PC micrometastases after systemic administration. 211At-6 also showed uptake in renal proximal tubules resulting in late nephrotoxicity, highlighting the importance of long-term toxicity studies and microscale dosimetry. PMID:27230930

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

Filipski, Elisabeth; Berland, Elodie; Univ Paris-Sud, UMR-S0776, Orsay F-91405

The relevance of P-glycoprotein (P-gp) for irinotecan chronopharmacology was investigated in female B6D2F{sub 1} mice. A three-fold 24 h change in the mRNA expression of Abcb1b was demonstrated in ileum mucosa, with a maximum at Zeitgeber Time (ZT) 15 (p < 0.001). No rhythm was found for abcb1a in ileum mucosa, or for Abcb1a/b in Glasgow osteosarcoma (GOS), a mouse tumor cell line moderately sensitive to irinotecan. Non-tumor-bearing mice received irinotecan (50 mg/kg/day i.v. × 4 days) as a single agent or combined with P-gp inhibitor PSC833 (6.25 mg/kg/day i.p. × 4 days) at ZT3 or ZT15, respectively corresponding tomore » the worst or the best irinotecan tolerability. Endpoints involved survival, body weight change and hematologic toxicity. Antitumor efficacy was studied in GOS-bearing mice receiving irinotecan (25, 30 or 40 mg/kg/day × 4 days) and +/− PSC833 at ZT3 or ZT15, with survival, body weight change, and tumor growth inhibition as endpoints. Non-tumor bearing mice lost an average of 17% or 9% of their body weight according to irinotecan administration at ZT3 or ZT15 respectively (p < 0.001). Dosing at ZT15 rather than ZT3 reduced mean leucopenia (9% vs 53%; p < 0.001). PSC833 aggravated irinotecan lethal toxicity from 4 to ∼ 60%. In tumor-bearing mice, body weight loss was ∼ halved in the mice on irinotecan or irinotecan–PSC833 combination at ZT15 as compared to ZT3 (p < 0.001). PSC833–irinotecan at ZT15 increased tumor inhibition by ∼ 40% as compared to irinotecan only at ZT15. In conclusion, P-gp was an important determinant of the circadian balance between toxicity and efficacy of irinotecan. - Highlights: • Irinotecan chronotolerance and chronoefficacy change as drug was applied with PSC833. • P-glycoprotein is an important player of the toxicity and efficacy of irinotecan. • Timing should be considered if chemotherapy is performed with a MDR1 inhibitor.« less

Formulation and comparative in vitro evaluation of various dexamethasone-loaded pH-sensitive polymeric nanoparticles intended for dermal applications.

PubMed

Sahle, Fitsum Feleke; Gerecke, Christian; Kleuser, Burkhard; Bodmeier, Roland

2017-01-10

pH-sensitive nanoparticles have a great potential for dermal and transfollicular drug delivery. In this study, pH-sensitive, dexamethasone-loaded Eudragit ® L 100, Eudragit ® L 100-55, Eudragit ® S 100, HPMCP-50, HPMCP-55 and cellulose acetate phthalate nanoparticles were prepared by nanoprecipitation and characterized. The pH-dependent swelling, erosion, dissolution and drug release kinetics were investigated in vitro using dynamic light scattering and Franz diffusion cells, respectively. Their toxicity potential was assessed by the ROS and MTT assays. 100-700nm nanoparticles with high drug loading and entrapment efficiency were obtained. The nanoparticles bear no toxicity potential. Cellulose phthalates nanoparticles were more sensitive to pH than acrylates nanoparticles. They dissolved in 10mM pH 7.5 buffer and released>80% of the drug within 7h. The acrylate nanoparticles dissolved in 40mM pH 7.5 buffer and released 65-70% of the drug within 7h. The nanoparticles remained intact in 10 and 40mM pH 6.0 buffers (HPMCP nanoparticles dissolved in 40mM pH 6.0 buffer) and released slowly. The nanoparticles properties could be modulated by blending the different polymers. In conclusion, various pH-sensitive nanoparticles that could release differently on the skin surface and dissolve and release in the hair follicles were obtained. Copyright © 2016 Elsevier B.V. All rights reserved.

A flavonoid component from Docynia delavayi (Franch.) Schneid represses transplanted H22 hepatoma growth and exhibits low toxic effect on tumor-bearing mice.

PubMed

Zhao, Xiangpei; Shu, Guangwen; Chen, Lvyi; Mi, Xue; Mei, Zhinan; Deng, Xukun

2012-09-01

The fruit of Docynia delavayi (Franch.) Schneid is a kind of popular food in southwestern areas of China. Additionally, its rhizome has been long used as a folk medicine in the treatment of liver cancer by local people. Chrysin is a kind of flavonoid which induces cancer cell death in vitro. However, its anti-tumor activity in vivo and toxicological effects on the tumor-bearing animals still remain poorly understood. In this study, we obtained four flavonoids from this herb. Among them, chrysin showed the strongest cytotoxic effect on an array of cultured tumor cells. Further investigations revealed that it significantly repressed transplanted H22 ascitic hepatic tumor cell growth in vivo. Moreover, this compound displayed little toxic effects. Additionally, we demonstrated that in transplanted tumor tissues, chrysin not only activated caspase-3 and induced apoptosis, but also inhibited the production of vascular endothelial growth factor (VEGF) and suppressed angiogenesis. These data showed that chrysin exhibited prominent anti-tumor activities and low toxic effects in vivo. Copyright © 2012 Elsevier Ltd. All rights reserved.

Hotfire testing of a SSME HPOTP with an annular hydrostatic bearing

NASA Technical Reports Server (NTRS)

Nolan, Steven A.; Hibbs, Robert I.; Genge, Gary G.

1994-01-01

A new fluid film bearing package has been tested in the Space Shuttle Main Engine (SSME) High Pressure Oxygen Turbopump (HPOTP). This fluid film element functions as both the pump end bearing and the preburner pump rear wear ring seal. Most importantly, it replaces a duplex ball bearing package which has been the primary life limiting component in the turbopump. The design and predicted performance of the turbopump are reviewed. Results are presented for measured pump and bearing performance during testing on the NASA Technology Test Bed (TTB) Engine located at MSFC. The most significant results were obtained from proximity probes located in the bearing bore which revealed large subsynchronous precession at ten percent of shaft speed during engine start which subsided prior to mainstage power levels and reappeared during engine shutdown at equivalent power levels below 65% of nominal. This phenomenon has been attributed to rotating stall in the diffuser. The proximity probes also revealed the location of the bearing in the bore for different operating speeds. Pump vibration characteristics were improved as compared to pumps tested with ball bearings. After seven starts and more than 700 seconds of testing, the pump showed no signs of performance degradation.

Distribution, diffusive fluxes, and toxicity of heavy metals and PAHs in pore water profiles from the northern bays of Taihu Lake.

PubMed

Lei, Pei; Zhang, Hong; Shan, Baoqing; Zhang, Bozheng

2016-11-01

Pore water plays a more significant role than do sediments in pollutant cycling dynamics. Also, concentrations of pollutants in pore water provide important information about their bioavailability or eco-toxicity; however, very few studies have focused on this topic. In this study, four duplicate sediment cores from three typical northern bays as well as the central part of Taihu Lake were collected to investigate the distribution, diffusive fluxes, and toxicity of heavy metals and polycyclic aromatic hydrocarbons (PAHs) in pore water profiles, which will be good in understanding the mobility and toxicity of these toxic pollutants and achieving better environmental management. The diffusive fluxes of heavy metals across the sediment-water interface was estimated through Fick's First Law, and the toxicity of heavy metals and PAHs in pore water was assessed by applying a water quality index (interstitial water toxicity criteria unit, IWCTU) and a hazard index (HI), respectively. The average concentrations of Cr, Cu, Ni, Pb, and Zn in surface pore water were 18.8, 23.4, 12.0, 13.5, and 42.5 μg L -1 , respectively. Also, concentrations of the selected heavy metals in both overlying water and pore water from Taihu Lake were all lower than the standard values of the environmental quality standards for surface water. The concentrations as the pore water depth increased, and the highest detected concentrations of heavy metals were recorded between 3 and 5 cm below the sediment surface. The average diffusive fluxes of these metals were 27.3, 24.8, 7.03, 7.81, and -3.32 μg (m 2 day) -1 , respectively, indicating export from sediment into overlying water, with the exception of Zn. There was a potential risk of toxicity, mainly from Pb and Cu, indicating that heavy metals in pore water had slight to moderate impact on sediment-dwelling organisms by values of the IWCTU and the Nemeraw index. The total PAH concentrations in pore water were higher than those in overlying water, and such gradient implies a potential flux of PAHs from pore water to overlying water. The average HI value of PAHs in surface pore water showed no or low ecological risk. While there may be occasional risk due to the HI values in some sites being greater than 1, the dominant contributors were carcinogenic PAHs. Because of their potential biological impact, heavy metals and PAHs and their comprehensive toxic effects in pore water should be given priority attention to keep the safety of Taihu Lake.

41 CFR 101-42.1102-7 - Lead-containing paint and items bearing lead-containing paint.

Code of Federal Regulations, 2012 CFR

2012-07-01

... toxic heavy metal which, in humans, exerts its effects on the renal, hematopoietic, and nervous systems... Property Management Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS...

41 CFR 101-42.1102-7 - Lead-containing paint and items bearing lead-containing paint.

Code of Federal Regulations, 2014 CFR

2014-07-01

... toxic heavy metal which, in humans, exerts its effects on the renal, hematopoietic, and nervous systems... Management Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS UTILIZATION...

41 CFR 101-42.1102-7 - Lead-containing paint and items bearing lead-containing paint.

Code of Federal Regulations, 2013 CFR

2013-07-01

... toxic heavy metal which, in humans, exerts its effects on the renal, hematopoietic, and nervous systems... Management Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS UTILIZATION...

41 CFR 101-42.1102-7 - Lead-containing paint and items bearing lead-containing paint.

Code of Federal Regulations, 2010 CFR

2010-07-01

... toxic heavy metal which, in humans, exerts its effects on the renal, hematopoietic, and nervous systems... Management Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS UTILIZATION...

41 CFR 101-42.1102-7 - Lead-containing paint and items bearing lead-containing paint.

Code of Federal Regulations, 2011 CFR

2011-07-01

... toxic heavy metal which, in humans, exerts its effects on the renal, hematopoietic, and nervous systems... Management Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS UTILIZATION...

The Calculation of VOCs Diffusion Coefficient for Building Materials

NASA Astrophysics Data System (ADS)

Zhang, Xin; Deng, Quancai; Chen, Haijiang; Wu, Xiaoyun

2018-05-01

Volatile Organic Compounds (VOCS), as one of the major sources of air contaminations, has an important bearing on one’s general health. The adsorption capacity and velocity of the material for VOCs can be described separately using. In this paper, the detailed process and method of VOCs diffusion and partition coefficients by genetic algorithm is introduced, the algorithm is realized easily by computer program and the result by the method is precise and practical.

Apparatus and method for stripping tritium from molten salt

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

Holcomb, David E.; Wilson, Dane F.

A method of stripping tritium from flowing stream of molten salt includes providing a tritium-separating membrane structure having a porous support, a nanoporous structural metal-ion diffusion barrier layer, and a gas-tight, nonporous palladium-bearing separative layer, directing the flowing stream of molten salt into contact with the palladium-bearing layer so that tritium contained within the molten salt is transported through the tritium-separating membrane structure, and contacting a sweep gas with the porous support for collecting the tritium.

Antitumor and immunomodulatory effects of Justicia spicigera Schltdl (Acanthaceae).

PubMed

Alonso-Castro, Angel Josabad; Ortiz-Sánchez, Elizabeth; Domínguez, Fabiola; Arana-Argáez, Victor; Juárez-Vázquez, Maria del Carmen; Chávez, Marco; Carranza-Álvarez, Candy; Gaspar-Ramírez, Octavio; Espinosa-Reyes, Guillermo; López-Toledo, Gabriela; Ortiz-Andrade, Rolffy; García-Carrancá, Alejandro

2012-06-14

Medicinal plants are an important source of antitumor compounds. This study evaluated the acute toxicity in vitro and in vivo, as well as the cytotoxic, antitumor and immunomodulatory effects of ethanolic extracts of Justicia spicigera leaves (JSE). The in vitro and in vivo toxicity of JSE was evaluated with comet assay in peripheral blood mononuclear cells (PBMC) and acute toxicity in mice, according to the Lorke procedure, respectively. The apoptotic effect of JSE on human cancer cells and human noncancerous cells was evaluated using flow cytometry with annexin-Alexa 488/propidium iodide. Also, different doses of JSE were injected intraperitoneally daily into athymic mice bearing tumors of HeLa cells during 18 days. The growth and weight of tumors were measured. The in vitro immunomodulatory effects of JSE were evaluated estimating the effects of JSE on the phagocytosis of the yeast Saccharomyces cerevisiae, NO production and H(2)O(2) release in macrophages, as well as the proliferation of splenocytes and NK activity. The comet assay showed that only JSE tested at 200 and 1000 μg/ml induced a significantly DNA damage in PBMC, compared to untreated cells, whereas the LD(50) was >5000 mg/kg by intraperitoneal route (i.p.) and by oral route. JSE showed pro-apoptotic (Annexin/PI) effects by 35% against HeLa cells, but lack toxic effects against human normal cells. JSE administrated at 10, 50 and 100 mg/kg i.p. inhibited the tumor growth by 28%, 41% and 53%, respectively, in mice bearing HeLa tumor. JSE stimulated, in a concentration dependent manner, the phagocytosis of Saccharomyces cerevisiae yeasts, the NO production and H(2)O(2) release by human differentiated macrophages. In addition, JSE stimulated the proliferation of murine splenocytes and induced the NK cell activity. Justicia spicigera shows low toxic effects in vitro and in vivo, exerts apoptotic effects on HeLa cells, has antitumor effects in mice bearing HeLa tumor and induces immunomodulatory activities in vitro. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice.

PubMed

Park, Hae-Ran; Ju, Eun-Jin; Jo, Sung-Kee; Jung, Uhee; Kim, Sung-Ho; Yee, Sung-Tae

2009-03-17

Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice. HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of 3 edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Anticancer effects of HemoHIM with cisplatin were evaluated in melanoma-bearing mice. We used a Cr51-release assay to measure the activity of NK/Tc cell and ELISA to evaluate the production of cytokines. In melanoma-bearing mice, cisplatin (4 mg/kg B.W.) reduced the size and weight of the solid tumors, and HemoHIM supplementation with cisplatin enhanced the decrease of both the tumor size (p < 0.1) and weight (p < 0.1). HemoHIM itself did not inhibit melanoma cell growth in vitro, and did not disturb the effects of cisplatin in vitro. However HemoHIM administration enhanced both NK cell and Tc cell activity in mice. Interestingly, HemoHIM increased the proportion of NK cells in the spleen. In melanoma-bearing mice treated with cisplatin, HemoHIM administration also increased the activity of NK cells and Tc cells and the IL-2 and IFN-gamma secretion from splenocytes, which seemed to contribute to the enhanced efficacy of cisplatin by HemoHIM. Also, HemoHIM reduced nephrotoxicity as seen by tubular cell of kidney destruction. HemoHIM may be a beneficial supplement during cisplatin chemotherapy for enhancing the anti-tumor efficacy and reducing the toxicity of cisplatin.

Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice

PubMed Central

2009-01-01

Background Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice. Methods HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of 3 edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Anticancer effects of HemoHIM with cisplatin were evaluated in melanoma-bearing mice. We used a Cr51-release assay to measure the activity of NK/Tc cell and ELISA to evaluate the production of cytokines. Results In melanoma-bearing mice, cisplatin (4 mg/kg B.W.) reduced the size and weight of the solid tumors, and HemoHIM supplementation with cisplatin enhanced the decrease of both the tumor size (p < 0.1) and weight (p < 0.1). HemoHIM itself did not inhibit melanoma cell growth in vitro, and did not disturb the effects of cisplatin in vitro. However HemoHIM administration enhanced both NK cell and Tc cell activity in mice. Interestingly, HemoHIM increased the proportion of NK cells in the spleen. In melanoma-bearing mice treated with cisplatin, HemoHIM administration also increased the activity of NK cells and Tc cells and the IL-2 and IFN-γ secretion from splenocytes, which seemed to contribute to the enhanced efficacy of cisplatin by HemoHIM. Also, HemoHIM reduced nephrotoxicity as seen by tubular cell of kidney destruction. Conclusion HemoHIM may be a beneficial supplement during cisplatin chemotherapy for enhancing the anti-tumor efficacy and reducing the toxicity of cisplatin. PMID:19292900

Component mobility at 900 °C and 18 kbar from experimentally grown coronas in a natural gabbro

NASA Astrophysics Data System (ADS)

Keller, Lukas M.; Wunder, Bernd; Rhede, Dieter; Wirth, Richard

2008-09-01

Several approximately 100-μm-wide reaction zones were grown under experimental conditions of 900 °C and 18 kbar along former olivine-plagioclase contacts in a natural gabbro. The reaction zone comprises two distinct domains: (i) an irregularly bounded zone with idiomorphic grains of zoisite and minor corundum and kyanite immersed in a melt developed at the plagioclase side and (ii) a well-defined reaction band comprising a succession of mineral layers forming a corona structure around olivine. Between the olivine and the plagioclase reactant phases we observe the following layer sequence: olivine|pyroxene|garnet|partially molten domain|plagioclase. Within the pyroxene layer two micro-structurally distinct layers comprising enstatite and clinopyroxene can be discerned. Chemical potential gradients persisted for the CaO, Al 2O 3, SiO 2, MgO and FeO components, which drove diffusion of Ca, Al and Si bearing species from the garnet-matrix interface to the pyroxene-olivine interface and diffusion of Mg- and Fe-bearing species in the opposite direction. The systematic mineralogical organization and chemical zoning across the corona suggest that the olivine corona was formed by a "diffusion-controlled" reaction. We estimate a set of diffusion coefficients and conclude that LAlAl < LCaCa < ( LSiSi, LFeFe) < LMgMg during reaction rim growth.

Diffusive gradients in thin films technique provide robust prediction of metal bioavailability and toxicity in estuarine sediments.

PubMed

Amato, Elvio D; Simpson, Stuart L; Jarolimek, Chad V; Jolley, Dianne F

2014-04-15

Many sediment quality assessment frameworks incorporate contaminant bioavailability as a critical factor regulating toxicity in aquatic ecosystems. However, current approaches do not always adequately predict metal bioavailability to organisms living in the oxidized sediment surface layers. The deployment of the diffusive gradients in thin films (DGT) probes in sediments allows labile metals present in pore waters and weakly bound to the particulate phase to be assessed in a time-integrated manner in situ. In this study, relationships between DGT-labile metal fluxes within 5 mm of the sediment-water interface and lethal and sublethal effects to the amphipod Melita plumulosa were assessed in a range of contaminated estuarine sediments during 10-day laboratory-based bioassays. To account for differing toxicities of metals, DGT fluxes were normalized to water (WQG) or sediment quality guidelines or toxicity thresholds specific for the amphipod. The better dose-response relationship appeared to be the one based on WQG-normalized DGT fluxes, which successfully predicted toxicity despite the wide range of metals and large variations in sediment properties. The study indicated that the labile fraction of metals measured by DGT is useful for predicting metal toxicity to benthic invertebrates, supporting the applicability of this technique as a rapid monitoring tool for sediments quality assessments.

Intranasal Fentanyl Intoxication Leading to Diffuse Alveolar Hemorrhage.

PubMed

Ruzycki, Shannon; Yarema, Mark; Dunham, Michael; Sadrzadeh, Hossein; Tremblay, Alain

2016-06-01

Increasing rates of opioid abuse, particularly fentanyl, may lead to more presentations of unusual effects of opioid toxicity. Diffuse alveolar hemorrhage is a rare complication of fentanyl overdose. A 45-year-old male presented in hypoxic respiratory failure secondary to diffuse alveolar hemorrhage requiring intubation. Comprehensive drug screening detected fentanyl without exposure to cocaine. Further history upon the patient's recovery revealed exposure to snorted fentanyl powder immediately prior to presentation. Diffuse alveolar hemorrhage is a potential, though rare, presentation of opioid intoxication. Recognition of less common complications of opioid abuse such as diffuse alveolar hemorrhage is important in proper management of overdoses.

Diffusive counter dispersion of mass in bubbly media.

PubMed

Goldobin, Denis S; Brilliantov, Nikolai V

2011-11-01

We consider a liquid bearing gas bubbles in a porous medium. When gas bubbles are immovably trapped in a porous matrix by surface-tension forces, the dominant mechanism of transfer of gas mass becomes the diffusion of gas molecules through the liquid. Essentially, the gas solution is in local thermodynamic equilibrium with vapor phase all over the system, i.e., the solute concentration equals the solubility. When temperature and/or pressure gradients are applied, diffusion fluxes appear and these fluxes are faithfully determined by the temperature and pressure fields, not by the local solute concentration, which is enslaved by the former. We derive the equations governing such systems, accounting for thermodiffusion and gravitational segregation effects, which are shown not to be neglected for geological systems-marine sediments, terrestrial aquifers, etc. The results are applied for the treatment of non-high-pressure systems and real geological systems bearing methane or carbon dioxide, where we find a potential possibility of the formation of gaseous horizons deep below a porous medium surface. The reported effects are of particular importance for natural methane hydrate deposits and the problem of burial of industrial production of carbon dioxide in deep aquifers.

Specific targeting and toxicity of sulphonated aluminium phthalocyanine photosensitised liposomes directed to cells by monoclonal antibody in vitro.

PubMed Central

Morgan, J.; Gray, A. G.; Huehns, E. R.

1989-01-01

A partially purified fraction of the water soluble photosensitive dye sulphonated aluminium phthalocyanine (AlSPc) was encapsulated in liposomes which were then linked to a targeting monoclonal antibody 791T/36 using a heterobifunctional linking agent. The photocytotoxic effects of the liposomes were determined on two cell lines bearing an antigen with which the targeting antibody binds: 791T, an osteosarcoma and C170, a colorectal carcinoma; and a control cell line not bearing the antigen; DW-BCL, an Epstein-Barr virus immortalised B-cell line. Antibody dependent cytotoxicity was observed in 791T and C170 cells and was proportional to the number of antigens on the cells, the AlSPc concentration and the time of exposure to activating red light. No significant toxicity was seen using untargeted liposomes, control cells or free AlSPc fraction under similar conditions. Targeted cells and controls kept in the dark also showed no significant toxicity. A possible mechanism of action is postulated and simple adaptations which demonstrate the versatility of the model are discussed. Some suggestions as to the clinical situations to which this system might be applied in the form of photodynamic therapy (PDT) are made. PMID:2930700

CORMIX2: AN EXPERT SYSTEM FOR HYDRODYNAMIC MIXING ZONE ANALYSIS OF CONVENTIONAL AND TOXIC MULTIPORT DIFFUSER DISCHARGES

EPA Science Inventory

CORMIX is a series of software systems for the analysis, prediction, and design of aqueous toxic or conventional pollutant discharges into watercourses, with emphasis on the geometry and dilution characteristics of the initial mixing zone. ubsystem CORMIX1 deals with submerged si...

Geographic distribution of selected elements in the livers of polar bears from Greenland, Canada and the United States.

PubMed

Rush, Scott A; Borgå, Katrine; Dietz, Rune; Born, Erik W; Sonne, Christian; Evans, Thomas; Muir, Derek C G; Letcher, Robert J; Norstrom, Ross J; Fisk, Aaron T

2008-06-01

To assess geographic distributions of elements in the Arctic we compared essential and non-essential elements in the livers of polar bears (Ursus maritimus) collected from five regions within Canada in 2002, in Alaska between 1994 and 1999 and from the northwest and east coasts of Greenland between 1988 and 2000. As, Hg, Pb and Se varied with age, and Co and Zn with gender, which limited spatial comparisons across all populations to Cd, which was highest in Greenland bears. Collectively, geographic relationships appeared similar to past studies with little change in concentration over time in Canada and Greenland for most elements; Hg and Se were higher in some Canadian populations in 2002 as compared to 1982 and 1984. Concentrations of most elements in the polar bears did not exceed toxicity thresholds, although Cd and Hg exceeded levels correlated with the formation of hepatic lesions in laboratory animals.

Relations Between Residential Proximity to EPA-Designated Toxic Release Sites and Diffuse Large B-Cell Lymphoma Incidence.

PubMed

Bulka, Catherine; Nastoupil, Loretta J; Koff, Jean L; Bernal-Mizrachi, Leon; Ward, Kevin C; Williams, Jessica N; Bayakly, A Rana; Switchenko, Jeffrey M; Waller, Lance A; Flowers, Christopher R

2016-10-01

Examining the spatial patterns of diffuse large B-cell lymphoma (DLBCL) incidence and residential proximity to toxic release locations may provide insight regarding environmental and sociodemographic risk factors. We linked and geocoded cancer incidence data for the period 1999-2008 from the Georgia Comprehensive Cancer Registry with population data from the US Census and the Environmental Protection Agency's Toxics Release Inventory. We conducted cluster analyses and constructed Poisson regression models to assess DLBCL incidence as a function of mean distance to the toxic release sites. In total, 3851 incident DLBCL cases occurred among adults residing in Georgia between 1999 and 2008. Significant focal clustering was observed around 57% of ethylene oxide sites, 5% of benzene sites, 9% of tetrachloroethylene sites, 7% of styrene sites, 10% of formaldehyde sites, 5% of trichloroethylene sites, and 10% of all release sites. Mean distance to sites was significantly associated with DLBCL risk for all chemicals. Proximity to Toxics Release Inventory sites can be linked to increased DLBCL risk as assessed through focal clustering and Poisson regression, and confirmatory studies using geospatial mapping can aid in further specifying risk factors for DLBCL.

A simple model for closure temperature of a trace element in cooling bi-mineralic systems

NASA Astrophysics Data System (ADS)

Liang, Yan

2015-09-01

Closure temperature is defined as the lower temperature limit at which the element of interest effectively ceases diffusive exchange with its surrounding medium during cooling. Here we generalize the classic equation of Dodson (1973) for cooling mono-mineralic systems to cooling bi-mineralic aggregates by considering diffusive exchange of a trace element between the two minerals in a closed system. We present a simple analytical model that includes key parameters affecting the closure temperature of a trace element in cooling bi-mineralic systems: cooling rate, temperature-dependent diffusion coefficients for the trace element in the two minerals, temperature-dependent partition coefficient of the trace element between the two minerals, effective grain sizes of the two minerals, and volume proportions of the minerals in the system. We show that closure temperatures of a trace element in cooling bi-mineralic systems are bounded by the closure temperatures of the trace element in the two mono-mineralic systems and that our generalized model reduces to Dodson's equation when one of the mineral serves as "an effective infinite" reservoir to the other mineral. Application to closure temperatures of REE in orthopyroxene and clinopyroxene bi-mineralic systems highlights the importance of REE diffusion and partitioning in the pyroxenes as well as clinopyroxene modal abundance and grain size in the systems. Closure temperatures for REE in two-pyroxene bearing equigranular rocks are controlled primarily by diffusion in orthopyroxene unless the modal abundance of clinopyroxene is very small. This has important bearings on the interpretation of temperatures derived from the REE-in-two-pyroxene thermometer.

Disabling Immune Tolerance by Programmed Death-1 Blockade With Pidilizumab After Autologous Hematopoietic Stem-Cell Transplantation for Diffuse Large B-Cell Lymphoma: Results of an International Phase II Trial

PubMed Central

Armand, Philippe; Nagler, Arnon; Weller, Edie A.; Devine, Steven M.; Avigan, David E.; Chen, Yi-Bin; Kaminski, Mark S.; Holland, H. Kent; Winter, Jane N.; Mason, James R.; Fay, Joseph W.; Rizzieri, David A.; Hosing, Chitra M.; Ball, Edward D.; Uberti, Joseph P.; Lazarus, Hillard M.; Mapara, Markus Y.; Gregory, Stephanie A.; Timmerman, John M.; Andorsky, David; Or, Reuven; Waller, Edmund K.; Rotem-Yehudar, Rinat; Gordon, Leo I.

2013-01-01

Purpose The Programmed Death-1 (PD-1) immune checkpoint pathway may be usurped by tumors, including diffuse large B-cell lymphoma (DLBCL), to evade immune surveillance. The reconstituting immune landscape after autologous hematopoietic stem-cell transplantation (AHSCT) may be particularly favorable for breaking immune tolerance through PD-1 blockade. Patients and Methods We conducted an international phase II study of pidilizumab, an anti–PD-1 monoclonal antibody, in patients with DLBCL undergoing AHSCT, with correlative studies of lymphocyte subsets. Patients received three doses of pidilizumab beginning 1 to 3 months after AHSCT. Results Sixty-six eligible patients were treated. Toxicity was mild. At 16 months after the first treatment, progression-free survival (PFS) was 0.72 (90% CI, 0.60 to 0.82), meeting the primary end point. Among the 24 high-risk patients who remained positive on positron emission tomography after salvage chemotherapy, the 16-month PFS was 0.70 (90% CI, 0.51 to 0.82). Among the 35 patients with measurable disease after AHSCT, the overall response rate after pidilizumab treatment was 51%. Treatment was associated with increases in circulating lymphocyte subsets including PD-L1E–bearing lymphocytes, suggesting an on-target in vivo effect of pidilizumab. Conclusion This is the first demonstration of clinical activity of PD-1 blockade in DLBCL. Given these results, PD-1 blockade after AHSCT using pidilizumab may represent a promising therapeutic strategy in this disease. PMID:24127452

Consumption and diffusion of dissolved oxygen in sedimentary rocks.

PubMed

Manaka, M; Takeda, M

2016-10-01

Fe(II)-bearing minerals (e.g., biotite, chlorite, and pyrite) are a promising reducing agent for the consumption of atmospheric oxygen in repositories for the geological disposal of high-level radioactive waste. To estimate effective diffusion coefficients (D e , in m 2 s -1 ) for dissolved oxygen (DO) and the reaction rates for the oxidation of Fe(II)-bearing minerals in a repository environment, we conducted diffusion-chemical reaction experiments using intact rock samples of Mizunami sedimentary rock. In addition, we conducted batch experiments on the oxidation of crushed sedimentary rock by DO in a closed system. From the results of the diffusion-chemical reaction experiments, we estimated the values of D e for DO to lie within the range 2.69×10 -11

Mechanisms of Chemical Modulation and Toxicity of the Immune System

DTIC Science & Technology

1989-12-15

antigens and suppressor/cytotoxic cells bearing Lyt-2 surface antigens. Autoimmune or immunodeficient diseases have been characte.ized by alterations...Written Publication (cumulative list) A. Suppression of mitogen-induced blastogenesis of feline lymphocytes by in Yi incubation with carcinogenic

Development of Less Toxic Treatment Strategies for Metastatic and Drug-Resistant Breast Cancer Using Noninvasive Optical Monitoring

DTIC Science & Technology

2016-09-01

AWARD NUMBER: W81XWH-15-1-0070 TITLE: Development of Less Toxic Treatment Strategies for Metastatic and Drug- Resistant Breast Cancer Using...0070 Development of Less Toxic Treatment Strategies for Metastatic and Drug- Resistant Breast Cancer Using Noninvasive Optical Monitori g 5c. PROGRAM...drug resistant breast cancer. Non-invasive Diffuse Optical Imaging technologies are able to monitor drug response and resistance through quantitative

Liquid metal pump

DOEpatents

Pennell, William E.

1982-01-01

The liquid metal pump comprises floating seal rings and attachment of the pump diffuser to the pump bowl for isolating structural deflections from the pump shaft bearings. The seal rings also eliminate precision machining on large assemblies by eliminating the need for a close tolerance fit between the mounting surfaces of the pump and the seals. The liquid metal pump also comprises a shaft support structure that is isolated from the pump housing for better preservation of alignment of shaft bearings. The shaft support structure also allows for complete removal of pump internals for inspection and repair.

[Fatal outcome of an hydrogen sulfide poisoning].

PubMed

Querellou, E; Jaffrelot, M; Savary, D; Savry, C; Perfus, J-P

2005-10-01

We report a case of fatal outcome poisoning by massive exposure to hydrogen sulfide of a sewer worker. This rare event was associated with a moderate intoxication of two members of the rescue team. The death was due to asystole and massive lung oedema. Autopsy analysis showed diffuse necrotic lesions in lungs. Hydrogen sulfide is a direct and systemic poison, produced by organic matter decomposition. The direct toxicity mechanism is still unclear. The systemic toxicity is due to an acute toxicity by oxygen depletion at cellular level. It is highly diffusable and potentially very dangerous. At low concentration, rotten egg smell must trigger hydrogen sulfide suspicion since at higher concentration it is undetectable, making intoxication possible. In case of acute intoxication, there is an almost instantaneous cardiovascular failure and a rapid death. Hydrogen sulfide exposure requires prevention measures and more specifically the use of respiratory equipment for members of the rescue team.

High-resolution magic angle spinning 1H-NMR spectroscopy studies on the renal biochemistry in the bank vole (Clethrionomys glareolus) and the effects of arsenic (As3+) toxicity.

PubMed

Griffin, J L; Walker, L; Shore, R F; Nicholson, J K

2001-06-01

1. High-resolution magic angle spinning (MAS) 1H-NMR spectroscopy was used to study renal metabolism and the toxicity of As3+, a common environmental contaminant, in the bank vole (Clethrionomys glareolus), a wild species of rodent. 2. Following a 14-day exposure to an environmentally relevant dose of As2O3 (28 mg kg(-1) feed), voles displayed tissue damage at autopsy. MAS 1H spectra indicated abnormal lipid profiles in these samples. 3. Tissue necrosis was also evident from measurements of the apparent diffusion coefficient of water in the intact tissue using MAS 1H diffusion-weighted spectroscopy, its first application to toxicology. 4. Comparison of renal tissue from the wood mouse (Apodemus sylvaticus) exposed to identical exposure levels of As3+ suggested that the bank vole is particularly vulnerable to As3+ toxicity.

24-HOUR DIFFUSIVE SAMPLING OF TOXIC VOCS IN AIR ONTO CARBOPACK X SOLID ADSORBENT FOLLOWED BY THERMAL DESORPTION/GC/MS ANALYSIS - LABORATORY STUDIES

EPA Science Inventory

Diffusive sampling of a mixture of 42 volatile organic compounds (VOCs) in humidified, purified air onto the solid adsorbent Carbopack X was evaluated under controlled laboratory conditions. The evaluation included variations in sample air temperature, relative humidity, and ozon...

Rapid fabrication of surface-relief plastic diffusers by ultrasonic embossing

NASA Astrophysics Data System (ADS)

Liu, Shih-Jung; Huang, Yu-Chin; Yang, Sen-Yeu; Hsieh, Kuo-Huang

2010-07-01

This paper discusses an innovative and effective ultrasonic embossing process, which enables the rapid fabrication of surface-relief plastic diffusers. The metallic mold bearing the microstructures is fabricated using a tungsten carbide turning machine. A 1500-W ultrasonic vibrator with an output frequency of 20 kHz was used to replicate the microstructure onto 1-mm-thick PMMA plates in the experiments. During ultrasonic embossing, the ultrasonic energy is converted into heat through intermolecular friction at the master mold/plastic plate interface due to asperities to melt the thermoplastic at the interface and thereby to replicate the microstructure. Under the proper processing conditions, high-performance plastic diffusers have been successfully fabricated. The cycle time required to successfully fabricate a diffuser is less than 2 s. The experimental results suggest that ultrasonic embossing could provide an effective way of fabricating high-performance plastic diffusers with a high throughput.

Hair Mercury Concentrations in Western Hudson Bay Polar Bear Family Groups.

PubMed

Bechshoft, Thea; Derocher, Andrew E; Richardson, Evan; Lunn, Nicholas J; St Louis, Vincent L

2016-05-17

Methylmercury is one of the more toxic forms of mercury (Hg), the biomagnification of which is prevalent in the Arctic where apex predators such as polar bears (Ursus maritimus) can carry high loads. The maternal transfer of contaminants to offspring is a concern, as offspring may be particularly sensitive to the effects of environmental pollutants during early development. However, few studies of polar bears report on Hg in dependent young. We examined hair total Hg (THg) concentrations in 24 polar bear family groups in western Hudson Bay: mother, cub-of-the-year (COY), yearling, and 2 year old. THg concentrations increased with bear age, with COYs having lower concentrations than other offspring groups (p ≤ 0.008). Using AICc-based regression models, we found maternal THg to be positively related to body condition and litter size, while overall offspring THg was positively related to maternal body condition in addition to being dependent on the sex and age of the offspring. COY THg concentrations were positively related to maternal THg while also depending on the sex of the offspring. Considering our results, future studies in polar bear ecotoxicology are encouraged to include offspring of different ages and sexes.

Decontamination of chemical tracers in droplets by a submerging thin film flow

NASA Astrophysics Data System (ADS)

Landel, Julien R.; McEvoy, Harry; Dalziel, Stuart B.

2016-11-01

We investigate the decontamination of chemical tracers contained in small viscous drops by a submerging falling film. This problem has applications in the decontamination of hazardous chemicals, following accidental releases or terrorist attacks. Toxic droplets lying on surfaces are cleaned by spraying a liquid decontaminant over the surface. The decontaminant film submerges the droplets, without detaching them, in order to neutralize toxic chemicals in the droplets. The decontamination process is controlled by advection, diffusion and reaction processes near the drop-film interface. Chemical tracers dissolve into the film flow forming a thin diffusive boundary layer at the interface. The chemical tracers are then neutralized through a reaction with a chemical decontaminant transported in the film. We assume in this work that the decontamination process occurs mainly in the film phase owing to low solubility of the decontaminant in the drop phase. We analyze the impact of the reaction time scale, assuming first-order reaction, in relation with the characteristic advection and diffusion time scales in the case of a single droplet. Using theoretical, numerical and experimental means, we find that the reaction time scale need to be significantly smaller than the characteristic time scale in the diffusive boundary layer in order to enhance noticeably the decontamination of a single toxic droplet. We discuss these results in the more general case of the decontamination of a large number of droplets. This material is based upon work supported by the Defense Threat Reduction Agency under Contract No. HDTRA1-12-D-0003-0001.

Chemistry and phase evolution during roasting of toxic thallium-bearing pyrite.

PubMed

Lopez-Arce, Paula; Garcia-Guinea, Javier; Garrido, Fernando

2017-08-01

In the frame of a research project on microscopic distribution and speciation of geogenic thallium (Tl) from contaminated mine soils, Tl-bearing pyrite ore samples from Riotinto mining district (Huelva, SW Spain) were experimentally fired to simulate a roasting process. Concentration and volatility behavior of Tl and other toxic heavy metals was determined by quantitative ICP-MS, whereas semi-quantitative mineral phase transitions were identified by in situ thermo X-Ray Diffraction (HT-XRD) and Scanning Electron Microscopy with Energy Dispersive Spectroscopy (SEM-EDS) analyses after each firing temperature. Sample with initial highest amount of quartz (higher Si content), lowest quantity of pyrite and traces of jarosite (lower S content) developed hematite and concentrated Tl (from 10 up to 72 mg kg -1 ) after roasting at 900 °C in an oxidizing atmosphere. However, samples with lower or absent quartz content and higher pyrite amount mainly developed magnetite, accumulating Tl between 400 and 500 °C and releasing Tl from 700 up to 900 °C (from 10-29 mg kg -1 down to 4-1 mg kg -1 ). These results show the varied accumulative, or volatile, behaviors of one of the most toxic elements for life and environment, in which oxidation of Tl-bearing Fe sulfides produce Fe oxides wastes with or without Tl. The initial chemistry and mineralogy of pyrite ores should be taken into account in coal-fired power stations, cement or sulfuric acid production industry involving pyrite roasting processes, and steel, brick or paint industries, which use iron ore from roasted pyrite ash, where large amounts of Tl entail significant environmental pollution. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oxygen diffusion: an enzyme-controlled variable parameter.

PubMed

Erdmann, Wilhelm; Kunke, Stefan

2014-01-01

Previous oxygen microelectrode studies have shown that the oxygen diffusion coefficient (DO₂) increases during extracellular PO₂ decreases, while intracellular PO₂ remained unchanged and thus cell function (spike activity of neurons). Oxygen dependency of complex multicellular organisms requires a stable and adequate oxygen supply to the cells, while toxic concentrations have to be avoided. Oxygen brought to the tissue by convection diffuses through the intercellular and cell membranes, which are potential barriers to diffusion. In gerbil brain cortex, PO₂ and DO₂ were measured by membrane-covered and by bare gold microelectrodes, as were also spike potentials. Moderate respiratory hypoxia was followed by a primary sharp drop of tissue PO₂ that recovered to higher values concomitant with an increase of DO₂. A drop in intracellular PO₂ recovered immediately. Studies on the abdominal ganglion of aplysia californica showed similar results.Heterogeneity is a feature of both normal oxygen supply to tissue and supply due to a wide range of disturbances in oxygen supply. Oxygen diffusion through membranes is variable thereby ensuring adequate intracellular PO₂. Cell-derived glucosamine oxidase seems to regulate the polymerization/depolymerisation ratio of membrane mucopolysaccharides and thus oxygen diffusion.Variability of oxygen diffusion is a decisive parameter for regulating the supply/demand ratio of oxygen supply to the cell; this occurs in highly developed animals as well as in species of a less sophisticated nature. Autoregulation of oxygen diffusion is as important as the distribution/perfusion ratio of the capillary meshwork and as the oxygen extraction ratio in relation to oxygen consumption of the cell. Oxygen diffusion resistance is the cellular protection against luxury oxygen supply (which can result in toxic oxidative species leading to mutagenesis).

Vacuum chamber-free centrifuge with magnetic bearings.

PubMed

Park, Cheol Hoon; Kim, Soohyun; Kim, Kyung-Soo

2013-09-01

Centrifuges are devices that separate particles of different densities and sizes through the application of a centrifugal force. If a centrifuge could be operated under atmospheric conditions, all vacuum-related components such as the vacuum chamber, vacuum pump, diffusion pump, and sealing could be removed from a conventional centrifuge system. The design and manufacturing procedure for centrifuges could then be greatly simplified to facilitate the production of lightweight centrifuge systems of smaller volume. Furthermore, the maintenance costs incurred owing to wear and tear due to conventional ball bearings would be eliminated. In this study, we describe a novel vacuum chamber-free centrifuge supported by magnetic bearings. We demonstrate the feasibility of the vacuum chamber-free centrifuge by presenting experimental results that verify its high-speed support capability and motoring power capacity.

Increasing incidence of hypothyroidism within one year after radioiodine therapy for toxic diffuse goiter. [/sup 131/I

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

Von Hofe, S.E.; Dorfman, S.G.; Carrette, R.F.

1978-02-01

Patients treated with 10 mCi of I-131 for toxic diffuse goiter in the period January 1974--June 1976 were evaluated for development of hypothyroidism. Fifty percent were hypothyroid within 3 months and 69 percent within 1 year of treatment. Our data suggest that there is a higher incidence of hypothyroidism after standard doses of I-131 in the 1970s as contrasted with treatment groups in the 1950s and 1960s. The pathophysiology of this increased incidence is not known with certainty; however, infrequent use of thionamide medication, together with recent increases in dietary iodine, may render the gland more radiosensitive.

Mechanisms of Chemical Modulation and Toxicity of the Immune System.

DTIC Science & Technology

1988-05-15

expressing the L3T4 surface antigens and suppressor/cytotoxic cells bearing Lyt-2 surface antigens. Autoimmune or immunodeficient diseases have been...Ill. Written Publications (cumulative list) A. Suppression of mitogen-induced blastogenesis of feline lymphocytes by in vitro incubation with

APPLICATION OF GENOMIC AND PROTEOMIC INDICATORS TO CHARACTERIZE EXPOSURE OF AQUATIC ORGANISMS TO ENVIRONMENTAL CONTAMINANTS

EPA Science Inventory

Advances in molecular biological methods are continually being brought to bear on human health research, from a basic understanding of systems biology to identification of toxicity pathways for environmental stressors and to correlations of molecular indicators with physiological...

USE OF HYDROGEN RESPIROMETRY TO DETERMINE METAL TOXICITY TO SULFATE REDUCING BACTERIA

EPA Science Inventory

Acid mine drainage (AMD), an acidic metal-bearing wastewater poses a severe pollution problem attributed to post-mining activities. The metals (metal sulfates) encountered in AMD and considered of concern for risk assessment are: arsenic, cadmium, aluminum, manganese, iron, zinc ...

Comparative toxicity of metal oxide nanoparticles (CuO, ZnO and TiO2) to developing zebrafish embryos

NASA Astrophysics Data System (ADS)

Vicario-Parés, Unai; Castañaga, Luis; Lacave, Jose Maria; Oron, Miriam; Reip, Paul; Berhanu, Deborah; Valsami-Jones, Eugenia; Cajaraville, Miren P.; Orbea, Amaia

2014-08-01

Increasing use of nanomaterials is resulting in their release into the environment, making necessary to determine the toxicity of these materials. With this aim, the effects of CuO, ZnO and TiO2 nanoparticles (NPs) on zebrafish development were assessed in comparison with the effects caused by the ionic forms (for copper and zinc), bulk counterparts and the stabilizer used for rutile TiO2 NPs. None of the NPs caused significant embryo mortality. CuO NPs were the most toxic affecting hatching and increasing malformation prevalence (≥1 mg Cu/L), followed by ZnO NPs that affected hatching at ≥5 mg Zn/L and stabilized TiO2 NPs that caused mortality and decreased hatching at 100 mg Ti/L. Exposure to the stabilizer alone provoked the same effect. Thus, toxicity of the TiO2 NP suspension can be linked to the surfactant. For all the endpoints, the greatest effects were exerted by the ionic forms, followed by the NPs and finally by the bulk compounds. By autometallography, metal-bearing deposits were observed in embryos exposed to CuO and ZnO NPs, being more abundant in the case of embryos exposed to CuO NPs. The largest and most abundant metal-bearing deposits were detected in embryos exposed to ionic copper. In conclusion, metal oxide NPs affected zebrafish development altering hatching and increasing the prevalence of malformations. Thus, the use and release of metal oxide NPs to the environment may pose a risk to aquatic organisms as a result of the toxicity caused by NPs themselves or by the additives used in their production.

(Almost) Dark Galaxies in the ALFALFA Survey: Isolated H I-bearing Ultra-diffuse Galaxies

NASA Astrophysics Data System (ADS)

Leisman, Lukas; Haynes, Martha P.; Janowiecki, Steven; Hallenbeck, Gregory; Józsa, Gyula; Giovanelli, Riccardo; Adams, Elizabeth A. K.; Bernal Neira, David; Cannon, John M.; Janesh, William F.; Rhode, Katherine L.; Salzer, John J.

2017-06-01

We present a sample of 115 very low optical surface brightness, highly extended, H I-rich galaxies carefully selected from the ALFALFA survey that have similar optical absolute magnitudes, surface brightnesses, and radii to recently discovered “ultra-diffuse” galaxies (UDGs). However, these systems are bluer and have more irregular morphologies than other UDGs, are isolated, and contain significant reservoirs of H I. We find that while these sources have normal star formation rates for H I-selected galaxies of similar stellar mass, they have very low star formation efficiencies. We further present deep optical and H I-synthesis follow-up imaging of three of these H I-bearing ultra-diffuse sources. We measure H I diameters extending to ˜40 kpc, but note that while all three sources have large H I diameters for their stellar mass, they are consistent with the H I mass-H I radius relation. We further analyze the H I velocity widths and rotation velocities for the unresolved and resolved sources, respectively, and find that the sources appear to inhabit halos of dwarf galaxies. We estimate spin parameters, and suggest that these sources may exist in high spin parameter halos, and as such may be potential H I-rich progenitors to the ultra-diffuse galaxies observed in cluster environments.

Determination of diffusivities in the Rustler Formation from exploratory-shaft construction at the Waste Isolation Pilot Plant in southeastern New Mexico

USGS Publications Warehouse

Stevens, Ken; Beyeler, Walt

1985-01-01

The construction of an exploratory shaft 12 feet in diameter into the Salado Formation (repository horizon for transuranic waste material) at the Waste Isolation Pilot Plant site in southeastern New Mexico affected water-levels in water-bearing zones above the repository horizon. By reading the construction history of the exploratory shaft, an approximation of construction-generated hydraulic stresses at the shaft was made. The magnitude of the construction-generated stresses was calibrated using the hydrographs from one hydrologic test pad. Whereas flow rates from the Magenta Dolomite and Culebra Dolomite Members in the Rustler Formation into the exploratory shaft were unknown, the ratio of transmissivity to storage (diffusivity) was determined by mathematically simulating the aquifers and the hydrologic stresses with flood-wave-response digital model. These results indicate that the Magenta Dolomite and Culebra Dolomite Members of the Rustler Formation can be modeled as homogeneous, isotropic, and confined water-bearing zones. One simple and consistent explanation, but by no means the only explanation, of the lack of a single diffusivity value in the Culebra aquifer is that the open-hole observation wells at the hydrologic test pads dampen the amplitude of water-level changes. (USGS)

A folate modified pH sensitive targeted polymeric micelle alleviated systemic toxicity of doxorubicin (DOX) in multi-drug resistant tumor bearing mice.

PubMed

Li, Xinru; Yang, Xiucong; Lin, Zhiqiang; Wang, Dan; Mei, Dong; He, Bing; Wang, Xiaoyou; Wang, Xueqing; Zhang, Qiang; Gao, Wei

2015-08-30

The purpose of this work was to demonstrate the advantages of a folate modified pH sensitive micelle system (HPPF) on reducing the systemic toxicity of antitumor drug doxorubicin (DOX) as well as increasing the antitumor efficacy on multi-drug resistant tumor. The micelle HPPF was fabricated by PHIS-PEG and Fol-PEG-PLA using dialysis method. Multi-drug resistant human breast-cancer cell (MCF-7Adr) was used to test the therapeutic effect of DOX loaded HPPF micelles (HPPF/DOX). Nude mice bearing MCF-7Adr tumor was used to evaluate the systemic toxicity of HPPF/DOX. The micelle HPPF was successfully prepared with good size uniformity and pH sensitivity. The in vitro experiments showed that HPPF significantly increased the intracellular level and cytotoxicity of DOX. The in vivo experiments demonstrated that HPPF had largely reduced the mortality and body weight loss, improved the animal status and decreased damages on heart and lung tissues comparing to free DOX. The HPPF/DOX could significantly increase the antitumor efficacy of DOX and largely alleviate the systemic side effects induced by high dose DOX in the treatment of multi-drug resistant tumor. Copyright © 2015 Elsevier B.V. All rights reserved.

A phase I clinical trial evaluating imatinib mesylate (Gleevec) in tumor-bearing cats.

PubMed

Lachowicz, Joshua L; Post, Gerald S; Brodsky, Edwin

2005-01-01

A phase I clinical trial evaluating the toxicity of orally-administered imatinib mesylate was performed in 9 tumor-bearing cats. Imatinib is a small molecule, tyrosine kinase inhibitor, which selectively blocks the function of overexpressed proteins associated with various malignancies. Cats included in the study had diagnoses of fibrosarcoma, squamous cell carcinoma, and mast cell tumor, and each cat was staged using CBC and serum biochemistry; urinalysis, thoracic radiographs, and abdominal ultrasonography were performed in some cats. Most cats were treated previously by surgery, radiation therapy, chemotherapy, or some combination of these treatments. None of the cats received any concurrent chemotherapy. Six cats were treated with imatinib mesylate at 1-2 mg/kg PO q24h. Dose escalations were made to 2, 4, and 10 mg/kg PO q24h in 5 cats. Two cats started therapy at 10 mg/kg PO q24h, and 1 cat started therapy at 15 mg/kg PO q24h; all 3 cats remained at these dosages. No signs of toxicity, as evaluated by CBC and serum biochemistry, were noted in 8 of the 9 cats, and minimal gastrointestinal toxicity was observed. Due to the low frequency of adverse effects, further evaluation of imatinib is ongoing at a dosage of 10 mg/kg PO q24h.

[Imbalance of microelements and vitamins in adolescents with diffuse nontoxic goiter and biliary dyskinesia].

PubMed

Plekhova, E I; Kashkalda, D A; Volkova, Iu V; Turchina, S I; Kosovtsova, A V; Kostenko, T P

2014-11-01

The purpose of the present work was to study the level of microelements and vitamins in adolescents with diffuse nontoxic goiter. It has been shown that comorbid biliary dyskinesia leads to significant dysregulation of vitamin and mineral metabolism: the level of essential elements was decreased and the level of toxic elements was increased. Comorbid biliary dyskinesia in adolescents with diffuse nontoxic goiter was accompanied by a disbalance of vitamins. The changes found in micronutrients have sex differences.

Respirometric biomonitor for the control of industrial effluent toxicity

NASA Astrophysics Data System (ADS)

Campanella, Luigi; Favero, G.; Mastrofini, D.; Tomassetti, M.

1995-10-01

A yeast cell biosystem has been recently developed for the total toxicity testing of a sample that may contain a number of different polluting species. The method uses an amperometric gas diffusion oxygen sensor as indicating electrode and is based on the perturbation of the respiratory activity of the immobilized yeast Saccharomyces cerevisiae; glucose acts as substrate. Several toxic substances were tested: metal ions, phenol and cationic, anionic or nonionic surfactants. Some results of a monitoring program of an industrial wastewater are also reported and discussed.

Experimental studies of diffusion welding of YBCO to copper using solder layers

NASA Astrophysics Data System (ADS)

Xie, Y.; Ouyang, Z.; Shi, L.; Kuang, Z.; Meng, M.

2017-02-01

The welding technology is of great importance in YBCO application. To make better joints, the diffusion welding of YBCO tape to copper has been carried out in a vacuum environment. In consideration of high welding temperature (above 200°C) could do damage to the material performance, a new kind of diffusion welding method with temperature below 200 °C has been developed recently. A new welding appliance which can offer pressure over 35Kg/mm2 and controlled temperature has been designed and built; several YBCO coated conductors joints soldered with different melting points of tins has been tested. The results showed that the diffusion can perfectly connect YBCO to copper as well as stainless steel and resistance of the joint was low, and the YBCO tape could bear 217°C for at least 15mins.

Chemical Complexity in Local Diffuse and Translucent Clouds: Ubiquitous Linear C3H and CH3CN, a Detection of HC3N and an Upper Limit on the Abundance of CH2CN

NASA Astrophysics Data System (ADS)

Liszt, Harvey; Gerin, Maryvonne; Beasley, Anthony; Pety, Jerome

2018-04-01

We present Jansky Very Large Array observations of 20–37 GHz absorption lines from nearby Galactic diffuse molecular gas seen against four cosmologically distant compact radio continuum sources. The main new observational results are that l-C3H and CH3CN are ubiqitous in the local diffuse molecular interstellar medium at {\\text{}}{A}{{V}} ≲ 1, while HC3N was seen only toward B0415 at {\\text{}}{A}{{V}} > 4 mag. The linear/cyclic ratio is much larger in C3H than in C3H2 and the ratio CH3CN/HCN is enhanced compared to TMC-1, although not as much as toward the Horsehead Nebula. More consequentially, this work completes a long-term program assessing the abundances of small hydrocarbons (CH, C2H, linear and cyclic C3H and C3 {{{H}}}2, and C4H and C4H‑) and the CN-bearing species (CN, HCN, HNC, HC3N, HC5N, and CH3CN): their systematics in diffuse molecular gas are presented in detail here. We also observed but did not strongly constrain the abundances of a few oxygen-bearing species, most prominently HNCO. We set limits on the column density of CH2CN, such that the anion CH2CN‑ is only viable as a carrier of diffuse interstellar bands if the N(CH2CN)/N(CH2CN‑) abundance ratio is much smaller in this species than in any others for which the anion has been observed. We argue that complex organic molecules (COMS) are not present in clouds meeting a reasonable definition of diffuse molecular gas, i.e., {\\text{}}{A}{{V}} ≲ 1 mag. Based on observations obtained with the NRAO Jansky Very Large Array (VLA).

Diffusion studies with synchrotron Mössbauer spectroscopy

NASA Astrophysics Data System (ADS)

Jackson, J. M.

2011-12-01

Knowledge of diffusion properties is critical for understanding many physical and chemical processes in planetary interiors. For example, diffusion behavior provides constraints on chemical exchange and viscosity. Nuclear resonances open the window for observing diffusion properties under the extreme conditions that exist deep inside the Earth. Synchrotron Mössbauer spectroscopy (viz. nuclear forward scattering) makes use of synchrotron radiation coherently scattered in the forward direction after nuclear resonant excitation. The decay of the forward-scattered radiation is faster when atoms move on the time scale of the excited-state lifetime because of a loss of coherence. Such diffusion-activated processes lead to accelerated decay and line broadening in the measured signal. In the case of the Mössbauer active isotope 57Fe, the nuclear resonance at 14.4 keV has a natural lifetime of 141 ns. Therefore, one can observe diffusion events ranging from approximately one-sixth to 100 times the natural lifetime of 57Fe, which corresponds to diffusion coefficients of 10-16 and 10-13 m2/s, respectively and a two to three order of magnitude range of suitability. In this contribution, we will describe such measurements that access the microscopic details of the diffusion process for iron-bearing phases.

Aconite poisoning following the percutaneous absorption of Aconitum alkaloids.

PubMed

Chan, Thomas Y K

2012-11-30

In vitro experiment using the modified Franz-type diffusion cell has demonstrated that the human skin is permeable to aconitine and mesaconitine. To characterise the risk of systemic toxicity following the topical applications of aconite tincture and raw aconite roots, relevant reports of percutaneous absorption of Aconitum alkaloids and aconite poisoning are reviewed. Published reports indicate that aconite tincture and raw aconite roots can be absorbed through the skin into systemic circulation to cause fatal and non-fatal aconite poisoning. Both aconite tincture and raw aconite roots contain very high concentrations of Aconitum alkaloids, which allow penetration of the stratum corneum along the diffusion gradient. The risk of systemic toxicity is even higher if Aconitum alkaloids are held in occlusive contact with the skin and the epidermis (stratum corneum) is already damaged. The public should be warned of the danger in using these topical aconite preparations and the risk of systemic toxicity following percutaneous absorption of Aconitum alkaloids. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Interstitial pneumonitis after acetylene welding: a case report.

PubMed

Brvar, Miran

2014-01-01

Acetylene is a colorless gas commonly used for welding. It acts mainly as a simple asphyxiant. In this paper, however, we present a patient who developed a severe interstitial pneumonitis after acetylene exposure during aluminum welding. A 44-year old man was welding with acetylene, argon and aluminum electrode sticks in a non-ventilated aluminum tank for 2 h. Four hours after welding dyspnea appeared and 22 h later he was admitted at the Emergency Department due to severe respiratory insufficiency with pO2 = 6.7 kPa. Chest X-ray showed diffuse interstitial infiltration. Pulmonary function and gas diffusion tests revealed a severe restriction (55% of predictive volume) and impaired diffusion capacity (47% of predicted capacity). Toxic interstitial pneumonitis was diagnosed and high-dose systemic corticosteroid methylprednisolone and inhalatory corticosteroid fluticasone therapy was started. Computed Tomography (CT) of the lungs showed a diffuse patchy ground-glass opacity with no signs of small airway disease associated with interstitial pneumonitis. Corticosteroid therapy was continued for the next 8 weeks gradually reducing the doses. The patient's follow-up did not show any deterioration of respiratory function. In conclusion, acetylene welding might result in severe toxic interstitial pneumonitis that improves after an early systemic and inhalatory corticosteroid therapy.

Education Policy Mobility: Reimagining Sustainability in Neoliberal Times

ERIC Educational Resources Information Center

McKenzie, Marcia; Bieler, Andrew; McNeil, Rebecca

2015-01-01

This paper is concerned with the twinning of sustainability with priorities of economic neoliberalization in education, and in particular via the mobility or diffusion of education policy. We discuss the literature on policy mobility as well as overview concerns regarding neoliberalism and education. The paper brings these analyses to bear in…

VizieR Online Data Catalog: HI-bearing ultra-diffuse ALFALFA galaxies (Leisman+, 2017)

NASA Astrophysics Data System (ADS)

Leisman, L.; Haynes, M. P.; Janowiecki, S.; Hallenbeck, G.; Jozsa, G.; Giovanelli, R.; Adams, E. A. K.; Neira, D. B.; Cannon, J. M.; Janesh, W. F.; Rhode, K. L.; Salzer, J. J.

2018-02-01

All sources discussed here have available SDSS and ALFALFA data. The ALFALFA observations, data reduction, and catalog products are detailed elsewhere (e.g., Giovanelli+ 2005AJ....130.2598G ; Saintonge 2007AJ....133.2087S ; Haynes+ 2011, J/AJ/142/170). (1 data file).

INTRAMOLECULAR MOTION AND REORIENTATIONAL BARRIERS IN 9-FLUORENONE, 4-METHYL-9-FLUORENONE AND 4,5-DIMETHYL-9-FLUORENONE

EPA Science Inventory

Carbon-13 nuclear magnetic resonance spin-lattice relaxation times and nuclear Overhauser enhancements were measured as functions of temperature for the hydrogen-bearing carbons in 9-fluorenone, 4-methyl-9-fluorenone, and 4,5-dimethyl-9-fluorenone. Reorientational diffusion const...

21 CFR 558.355 - Monensin.

Code of Federal Regulations, 2011 CFR

2011-04-01

... monensin intended for use in cattle and goats shall bear, in addition to the caution statement in paragraph (d)(6) of this section, the following statements: (i) Monensin medicated cattle and goat feeds are safe for use in cattle and goats only. Consumption by unapproved species may result in toxic reactions...

Anti-hepatoma activity in mice of a polysaccharide from the rhizome of Anemone raddeana.

PubMed

Liu, Yang; Li, Yiming; Yang, Wenbin; Zhang, Li; Cao, Gang

2012-04-01

A neutral polysaccharide fraction (ARP) prepared from the rhizome of Anemone raddeana was tested for its anticancer activity in H22 tumor-bearing mice by oral administration. ARP could not only significantly inhibit the growth of H22 transplantable tumor, but also remarkably promote splenocytes proliferation, NK cell and CTL activity, as well as serum IL-2 and TNF-α production in tumor-bearing mice. In addition, ARP treatment to tumor bearing mice had no toxicity to body weight, the liver and kidney. Moreover it could reverse the hematological parameters induced by 5-fluorouracil (5-FU) to near normal. The above results suggested that the antitumor activity of ARP might be achieved by improving immune response, and they could act as antitumor agent with immunomodulatory activity. Copyright © 2012 Elsevier B.V. All rights reserved.

Subsychronous vibration of multistage centrifugal compressors forced by rotating stall

NASA Technical Reports Server (NTRS)

Fulton, J. W.

1987-01-01

A multistage centrifugal compressor, in natural gas re-injection service on an offshore petroleum production platform, experienced subsynchronous vibrations which caused excessive bearing wear. Field performance testing correlated the subsynchronous amplitude with the discharge flow coefficient, demonstrating the excitation to be aerodynamic. Adding two impellers allowed an increase in the diffuser flow angle (with respect to tangential) to meet the diffuser stability criteria based on factory and field tests correlated using the theory of Senoo (for rotating stall in a vaneless diffuser). This modification eliminated all significant subsynchronous vibrations in field service, thus confirming the correctness of the solution. Other possible sources of aerodynamically induced vibrations were considered, but the judgment that those are unlikely has been confirmed by subsequent experience with other similar compressors.

Assessment of Cu sub-lethal toxicity (LC50) in the cold-water gorgonian Dentomuricea meteor under a deep-sea mining activity scenario.

PubMed

Martins, Inês; Godinho, António; Goulart, Joana; Carreiro-Silva, Marina

2018-05-21

Previous aquaria-based experiments have shown dissolution and leaching of metals, especially copper (Cu), from the simulated sediment plumes generated during mining activities resulting in a pronounced increase of Cu contamination in the surrounding seawater. Metals are bioavailable to corals with food, through ingestion (particulate phase) and through tissue-facilitated transport (passive diffusion). With corals being particularly vulnerable to metal contamination, resuspension of metal-bearing sediments during mining activities represents an important ecological threat. This study was undertaken to evaluate the impact of acute copper exposure (LC 50;96 h ) on the survival of the cold-water octocoral Dentomuricea aff. meteor. The experimental design was divided in two stages. In stage one, a Cu range-finding toxicity test was performed using Cu dilutions in filtered seawater with concentrations of 0 (control); 60; 150; 250; 450; 600 μg/L. Coral mortality was investigated visually based on the percent surface area of tissue changing from natural yellow colour to black colour indicative of tissue necrosis and death. In stage two, we used the results obtained in the range-finding experiment, to define sub-lethal Cu exposure treatments and exposed D. meteor to Cu concentration of 0 (control); 50; 100; 150; 200; 250 μg/L for 96 h. The corals physical conditions were inspected daily and seawater conditions recorded. Corals were considered dead when all of their tissue turned black. The LC 50 value was calculated with regression analysis following Probits methodology. Our results indicate that Cu LC 50;96 h for the octocoral D. meteor is 137 μg/L. Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemoprotective and chemosensitizing properties of selenium nanoparticle (Nano-Se) during adjuvant therapy with cyclophosphamide in tumor-bearing mice.

PubMed

Bhattacharjee, Arin; Basu, Abhishek; Biswas, Jaydip; Sen, Tuhinadri; Bhattacharya, Sudin

2017-01-01

Cyclophosphamide (CP) is one of the widely used anticancer agents; however, it has serious deleterious effects on normal host cells due to its nonspecific action. The essential trace element Selenium (Se) is suggested to have chemopreventive and chemotherapeutic efficacy and currently used in pharmaceutical formulations. Previous report had shown Nano-Se could protect CP-induced hepatotoxicity and genotoxicity in normal Swiss albino mice; however, its role in cancer management is still not clear. The aim of present study is to investigate the chemoprotective efficacy of Nano-Se against CP-induced toxicity as well as its chemoenhancing capability when used along with CP in Swiss albino mice against Ehrlich's ascites carcinoma (EAC) cells. CP was administered (25 mg/kg b.w., i.p.) and Nano-Se was given (2 mg Se/kg b.w., p.o.) in concomitant and pretreatment schedule. Increase levels of serum hepatic marker, hepatic lipid peroxidation, DNA damage, and chromosomal aberration in CP-treated mice were significantly (P < 0.05) reversed by Nano-Se. The lowered status of various antioxidant enzymes in tumor-bearing mice after CP treatment was also effectively increased by Nano-Se. Administration of Nano-Se along with CP caused a significant reduction in tumor volume, packed cell volume, viable tumor cell count, and increased the survivability of the tumor-bearing hosts. The results suggest that Nano-Se exhibits significant antitumor and antioxidant effects in EAC-bearing mice. The potential for Nano-Se to ameliorate the CP-evoked toxicity as well as to improve the chemotherapeutic effect could have beneficial implications for patients undergoing chemotherapy with CP.

The diffuse interstellar bands: a tracer for organics in the diffuse interstellar medium?

NASA Technical Reports Server (NTRS)

Salama, F.

1998-01-01

The diffuse interstellar bands (DIBs) are absorption bands seen in the spectra of stars obscured by interstellar dust. DIBs are recognized as a tracer for free, organic molecules in the diffuse interstellar medium (ISM). The potential molecular carriers for the DIBs are discussed with an emphasis on neutral and ionized polycyclic aromatic hydrocarbons (PAHs) for which the most focused effort has been made to date. From the combined astronomical, laboratory and theoretical study, it is concluded that a distribution of free neutral and ionized complex organics (PAHs, fullerenes, unsaturated hydrocarbons) represents the most promising class of candidates to account for the DIBs. The case for aromatic hydrocarbons appears particularly strong. The implied widespread distribution of complex organics in the diffuse ISM bears profound implications for our understanding of the chemical complexity of the ISM, the evolution of prebiotic molecules and its impact on the origin and the evolution of life on early Earth through the exogenous delivery (cometary encounters and metoritic bombardments) of prebiotic organics.

Proteomic Signatures of the Zebrafish (Danio rerio) Embryo: Sensitivity and Specificity in Toxicity Assessment of Chemicals.

PubMed

Hanisch, Karen; Küster, Eberhard; Altenburger, Rolf; Gündel, Ulrike

2010-01-01

Studies using embryos of the zebrafish Danio rerio (DarT) instead of adult fish for characterising the (eco-) toxic potential of chemicals have been proposed as animal replacing methods. Effect analysis at the molecular level might enhance sensitivity, specificity, and predictive value of the embryonal studies. The present paper aimed to test the potential of toxicoproteomics with zebrafish eleutheroembryos for sensitive and specific toxicity assessment. 2-DE-based toxicoproteomics was performed applying low-dose (EC(10)) exposure for 48 h with three-model substances Rotenone, 4,6-dinitro-o-cresol (DNOC) and Diclofenac. By multivariate "pattern-only" PCA and univariate statistical analyses, alterations in the embryonal proteome were detectable in nonetheless visibly intact organisms and treatment with the three substances was distinguishable at the molecular level. Toxicoproteomics enabled the enhancement of sensitivity and specificity of the embryonal toxicity assay and bear the potency to identify protein markers serving as general stress markers and early diagnosis of toxic stress.

Proteomic Signatures of the Zebrafish (Danio rerio) Embryo: Sensitivity and Specificity in Toxicity Assessment of Chemicals

PubMed Central

Hanisch, Karen; Küster, Eberhard; Altenburger, Rolf; Gündel, Ulrike

2010-01-01

Studies using embryos of the zebrafish Danio rerio (DarT) instead of adult fish for characterising the (eco-) toxic potential of chemicals have been proposed as animal replacing methods. Effect analysis at the molecular level might enhance sensitivity, specificity, and predictive value of the embryonal studies. The present paper aimed to test the potential of toxicoproteomics with zebrafish eleutheroembryos for sensitive and specific toxicity assessment. 2-DE-based toxicoproteomics was performed applying low-dose (EC10) exposure for 48 h with three-model substances Rotenone, 4,6-dinitro-o-cresol (DNOC) and Diclofenac. By multivariate “pattern-only” PCA and univariate statistical analyses, alterations in the embryonal proteome were detectable in nonetheless visibly intact organisms and treatment with the three substances was distinguishable at the molecular level. Toxicoproteomics enabled the enhancement of sensitivity and specificity of the embryonal toxicity assay and bear the potency to identify protein markers serving as general stress markers and early diagnosis of toxic stress. PMID:22084678

Non-translational Molecular Diffusive Motion on Two Different Time Scales in Alkane Nanoparticles

NASA Astrophysics Data System (ADS)

Wang, S.-K.; Bai, M.; Taub, H.; Mamontov, E.; Herwig, K. W.; Hansen, F. Y.; Copley, J. R. D.; Jenkins, T.; Tyagi, M.; Volkmann, U. G.

2009-03-01

Using quasielastic neutron scattering, we have investigated molecular diffusive motion in n-C32H66 nanoparticles whose structure and phase transitions have been studied previously.^2 The spectra reveal non-translational (dispersionless) diffusive motion occurring simultaneously on time scales of ˜1 ns and ˜40 ps. The onset of the faster motion occurs in the crystalline phase at least 15 K below the melting point and is tentatively identified with rotation about the long molecular axis. Similarly, we suggest that the slower motion involves molecular conformational changes whose onset appears to coincide with the abrupt transition to the bulk rotator phase about 3 K below melting. These two types of diffusive motion bear a strong resemblance to those observed previously in C24 monolayers adsorbed on a graphite surface.^3 ^2M. Bai et al., Europhys. Lett. 79, 26003 (2007). ^3F. Y. Hansen et al., Phys. Rev. Lett. 92, 046103 (2004)].

Efficient intracellular delivery and improved biocompatibility of colloidal silver nanoparticles towards intracellular SERS immuno-sensing.

PubMed

Bhardwaj, Vinay; Srinivasan, Supriya; McGoron, Anthony J

2015-06-21

High throughput intracellular delivery strategies, electroporation, passive and TATHA2 facilitated diffusion of colloidal silver nanoparticles (AgNPs) are investigated for cellular toxicity and uptake using state-of-art analytical techniques. The TATHA2 facilitated approach efficiently delivered high payload with no toxicity, pre-requisites for intracellular applications of plasmonic metal nanoparticles (PMNPs) in sensing and therapeutics.

Transscleral diffusion of ethacrynic acid and sodium fluorescein

PubMed Central

Lin, Cheng-Wen; Wang, Yong; Challa, Pratap; Epstein, David L.

2007-01-01

Purpose One of the current limitations in developing novel glaucoma drugs that target the trabecular meshwork (TM) is the induced corneal toxicity from eyedrop formulations. To avoid the corneal toxicity, an alternative approach would be to deliver TM drugs through the sclera. To this end, we quantified ex vivo diffusion coefficient of a potential TM drug, ethacrynic acid (ECA), and investigated mechanisms of ECA transport in the sclera. Methods An Ussing-type diffusion apparatus was built to measure the apparent diffusion coefficient of ECA in fresh porcine sclera at 4 °C. To understand mechanisms of ECA transport, we quantified the transscleral transport of a fluorescent tracer, sodium fluorescein (NaF), that has a similar molecular weight but is more hydrophilic compared to ECA. Furthermore, we developed a mathematical model to simulate the transport processes and used it to analyze the experimental data. The model was also used to investigate the dependence of diffusion coefficients on volume fraction of viable cells and the binding of NaF and ECA to scleral tissues. Results The diffusion coefficients of ECA and NaF in the sclera were 48.5±15.1x10-7 cm2/s (n=9) and 5.23±1.93x10-7 cm2/s (n=8), respectively. Both diffusion coefficients were insensitive to cell shrinkage caused by ECA during the diffusion experiments and cell damage caused by the storage of tissues ex vivo before the experiments. Binding of ECA to scleral tissues could not be detected. The apparent maximum binding capacity and the apparent equilibrium dissociation constant for NaF were 80±5 mM and 2.5±0.5 mM (n=3), respectively. Conclusions These data demonstrated that ECA diffusion was minimally hindered by structures in the sclera, presumably due to the lack of cells and binding sites for ECA in the sclera. PMID:17356511

Thermodynamic approach to oxygen delivery in vivo by natural and artificial oxygen carriers.

PubMed

Bucci, Enrico

2009-06-01

Oxygen is a toxic gas, still indispensable to aerobic life. This paper explores how normal physiology uses the physico-chemical and thermodynamic characteristics of oxygen for transforming a toxic gas into a non toxic indispensable metabolite. Plasma oxygen concentration is in the range of 10(-5) M, insufficient to sustain metabolism. Oxygen carriers, present in blood, release oxygen into plasma, thereby replacing consumed oxygen and buffering PO(2) near their P(50). They are the natural cell-bound carriers, like hemoglobin inside red cells, myoglobin inside myocytes, and artificial cell-free hemoglobin-based oxygen carriers (HBOC) dissolved in plasma. Metabolic oxygen replacement can be defined as cell-bound and cell-free delivery. Cell-bound delivery is retarded by the slow diffusion of oxygen in plasma and interstitial fluids. The 40% hematocrit of normal blood compensates for the delay, coping with the fast oxygen consumption by mitochondria. Facilitated oxygen diffusion by HBOCs corrects for the slow diffusion, making cell-free delivery relatively independent from P(50). At all oxygen affinities, HBOCs produce hyperoxygenations that are compensated by vasoconstrictions. There is a strict direct correlation between the rate of oxygen replacement and hemoglobin content of blood. The free energy loss of the gradient adds a relevant regulation of tissues oxygenation. Oxygen is retained intravascularly by the limited permeability to gases of vessel walls.

(Almost) Dark Galaxies in the ALFALFA Survey: Isolated H i-bearing Ultra-diffuse Galaxies

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

Leisman, Lukas; Haynes, Martha P.; Giovanelli, Riccardo

2017-06-20

We present a sample of 115 very low optical surface brightness, highly extended, H i-rich galaxies carefully selected from the ALFALFA survey that have similar optical absolute magnitudes, surface brightnesses, and radii to recently discovered “ultra-diffuse” galaxies (UDGs). However, these systems are bluer and have more irregular morphologies than other UDGs, are isolated, and contain significant reservoirs of H i. We find that while these sources have normal star formation rates for H i-selected galaxies of similar stellar mass, they have very low star formation efficiencies. We further present deep optical and H i-synthesis follow-up imaging of three of thesemore » H i-bearing ultra-diffuse sources. We measure H i diameters extending to ∼40 kpc, but note that while all three sources have large H i diameters for their stellar mass, they are consistent with the H i mass–H i radius relation. We further analyze the H i velocity widths and rotation velocities for the unresolved and resolved sources, respectively, and find that the sources appear to inhabit halos of dwarf galaxies. We estimate spin parameters, and suggest that these sources may exist in high spin parameter halos, and as such may be potential H i-rich progenitors to the ultra-diffuse galaxies observed in cluster environments.« less

Immuno-therapy of Acute Radiation Syndromes : Extracorporeal Immuno-Lympho-Plasmo-Sorption.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Slava

Methods Results Summary and conclusions Introduction: Existing Medical Management of the Acute Radiation Syndromes (ARS) does not include methods of specific immunotherapy and active detoxication. Though the Acute Radiation Syndromes were defined as an acute toxic poisonous with development of pathological processes: Systemic Inflammatory Response Syndrome (SIRS), Toxic Multiple Organ Injury (TMOI), Toxic Multiple Organ Dysfunction Syndrome(TMODS), Toxic Multiple Organ Failure (TMOF). Radiation Toxins of SRD Group play an important role as the trigger mechanisms in development of the ARS clinical symptoms. Methods: Immuno-Lympho-Plasmo-Sorption is a type of Immuno-therapy which includes prin-ciples of immunochromato-graphy, plasmopheresis, and hemodialysis. Specific Antiradiation Antitoxic Antibodies are the active pharmacological agents of immunotherapy . Antiradia-tion Antitoxic Antibodies bind selectively to Radiation Neurotoxins, Cytotoxins, Hematotox-ins and neutralize their toxic activity. We have developed the highly sensitive method and system for extracorporeal-immune-lypmh-plasmo-sorption with antigen-specific IgG which is clinically important for treatment of the toxic and immunologic phases of the ARS. The method of extracorporeal-immune-lypmh-plasmo-sorption includes Antiradiation Antitoxic Antibodies (AAA) immobilized on microporous polymeric membranes with a pore size that is capable to provide diffusion of blood-lymph plasma. Plasma of blood or lymph of irradiated mammals contains Radiation Toxins (RT) that have toxic and antigenic properties. Radiation Toxins are Antigen-specific to Antitoxic blocking antibodies (Immunoglobulin G). Plasma diffuses through membranes with immobilized AAA and AA-antibodies bind to the polysaccharide chain of tox-ins molecules and complexes of AAA-RT that are captured on membrane surfaces. RT were removed from plasma. Re-transfusion of plasma of blood and lymph had been provided. We show a statistical significant reduction in postradiation lethality.

A fast random walk algorithm for computing the pulsed-gradient spin-echo signal in multiscale porous media.

PubMed

Grebenkov, Denis S

2011-02-01

A new method for computing the signal attenuation due to restricted diffusion in a linear magnetic field gradient is proposed. A fast random walk (FRW) algorithm for simulating random trajectories of diffusing spin-bearing particles is combined with gradient encoding. As random moves of a FRW are continuously adapted to local geometrical length scales, the method is efficient for simulating pulsed-gradient spin-echo experiments in hierarchical or multiscale porous media such as concrete, sandstones, sedimentary rocks and, potentially, brain or lungs. Copyright © 2010 Elsevier Inc. All rights reserved.

Analysis of metal tolerance in Rhizobium leguminosarum strains isolated from an ultramafic soil.

PubMed

Rubio-Sanz, Laura; Brito, Belén; Palacios, Jose

2018-02-01

Natural habitats containing high amounts of heavy metals provide a valuable source of bacteria adapted to deal with metal toxicity. A functional analysis of the population of legume endosymbiotic bacteria in an ultramafic soil was undertaken by studying a collection of Rhizobium leguminosarum bv viciae (Rlv) isolates obtained using pea as trap plant. One of the isolates, Rlv UPM1137, was selected on the basis of its higher tolerance to nickel and cobalt and presence of inducible mechanisms for such tolerance. A random transposon mutagenesis of Rlv UPM1137 allowed the generation of 14 transposant derivatives with increased nickel sensitivity; five of these transposants were also more sensitive to cobalt. Sequencing of the insertion sites revealed that one of the transposants (D2250) was affected in a gene homologous to the cation diffusion facilitator gene dmeF first identified in the metal-resistant bacterium Cupriavidus metallidurans CH34. The symbiotic performance of D2250 and two other transposants bearing single transposon insertions was unaffected under high-metal conditions, suggesting that, in contrast to previous observations in other Rlv strain, metal tolerance in UPM1137 under symbiotic conditions might be supported by functional redundancy between several mechanisms. © FEMS 2018. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

STUDY PROGRAM FOR TURBO-COOLER FOR PRODUCING ENGINE COOLING AIR.

DTIC Science & Technology

VANES , STAGNATION POINT, DECELERATION, ACCELERATION, SUPERSONIC DIFFUSERS, TURBINE BLADES , EVAPOTRANSPIRATION, LIQUID COOLED, HEAT TRANSFER, GAS BEARINGS, SEALS...HYPERSONIC AIRCRAFT , COOLING + VENTILATING EQUIPMENT), (*GAS TURBINES , COOLING + VENTILATING EQUIPMENT), HYPERSONIC FLOW, AIR COOLED, AIRCRAFT ... ENGINES , FEASIBILITY STUDIES, PRESSURE, SUPERSONIC CHARACTERISTICS, DESIGN, HEAT EXCHANGERS, COOLING (U) AXIAL FLOW TURBINES , DUCT INLETS, INLET GUIDE

Enhanced cytotoxicity of anticancer drug delivered by novel nanoscale polymeric carrier

NASA Astrophysics Data System (ADS)

Stoika, R.; Boiko, N.; Senkiv, Y.; Shlyakhtina, Y.; Panchuk, R.; Finiuk, N.; Filyak, Y.; Bilyy, R.; Kit, Y.; Skorohyd, N.; Klyuchivska, O.; Zaichenko, A.; Mitina, N.; Ryabceva, A.

2013-04-01

We compared in vitro action of highly toxic anticancer drug doxorubicin under its delivery to the mammalian tumor cells in free form and after encapsulation in novel bio-functionalized nanoscale polymeric carrier. Such encapsulation was found to enhance significantly drug uptake by the targeted cells, as well as its cytotoxic action. 10 times higher cytotoxicity of the carrier-immobilized doxorubicin comparing to its free form was demonstrated by direct cell counting, and 5 times higher cytotoxicity of encapsulated doxorubicin was shown by FACS analysis. The polymeric carrier itself did not possess significant toxicity in vitro or in vivo (laboratory mice). The carrier protected against negative side effects of doxorubicin in mice with experimental NK/Ly lymphoma. The life duration of tumor-bearing animals treated with doxorubicin-carrier complex was significantly longer than life duration in animals treated with free doxorubicin. Besides, the effective treatment dose of the carrier-delivered doxorubicin in tumor-bearing mice was 10 times lower than such dose of free doxorubicin. Thus, novel nanoscale polymers possess high potential as drug carrier.

Spectral characteristics of iron-bearing phyllosilicates: Comparison to Orgueil (CI1), Murchison and Murray (CM2)

USGS Publications Warehouse

Calvin, W.M.; King, T.V.V.

1997-01-01

Phyllosilicate alteration minerals are commonly found in low petrologic types of carbonaceous chondrites. Previous spectral studies have examined Mg-bearing phyllosilicates with limited success in matching the spectral properties of CM and CI chondrites. Transmission electron microscope and other analytical techniques suggest that Fe-bearing clays are more abundant in CI and CM chondrites than magnesian varieties. Here, we present the results of an examination of the reflectance spectra of Fe-phyllosilicates, including serpentines and berthierines, of which the latter were formerly known as septechlorites. We have measured the diffuse reflectance spectra of powdered samples from 0.3 to 25 ??m. We find that these minerals provide a better spectral match to many of the features seen in CI and CM chondrites, and simple linear combinations of the spectra of both Fe- and Mg-phyllosilicates closely approximate the spectra of CM and CI chondrites.

Plant-Associated Bacterial Degradation of Toxic Organic Compounds in Soil

PubMed Central

McGuinness, Martina; Dowling, David

2009-01-01

A number of toxic synthetic organic compounds can contaminate environmental soil through either local (e.g., industrial) or diffuse (e.g., agricultural) contamination. Increased levels of these toxic organic compounds in the environment have been associated with human health risks including cancer. Plant-associated bacteria, such as endophytic bacteria (non-pathogenic bacteria that occur naturally in plants) and rhizospheric bacteria (bacteria that live on and near the roots of plants), have been shown to contribute to biodegradation of toxic organic compounds in contaminated soil and could have potential for improving phytoremediation. Endophytic and rhizospheric bacterial degradation of toxic organic compounds (either naturally occurring or genetically enhanced) in contaminated soil in the environment could have positive implications for human health worldwide and is the subject of this review. PMID:19742157

Helium Diffusion in Olivine

NASA Astrophysics Data System (ADS)

Cherniak, D. J.; Watson, E. B.

2011-12-01

Diffusion of helium has been characterized in natural Fe-bearing olivine (~Fo90) and synthetic forsterite. Polished, oriented slabs of olivine were implanted with 3He, at 100 keV at a dose of 5x1015/cm2 or at 3.0 MeV at a dose of 1x1016/cm2. A set of experiments on the implanted olivine were run in 1-atm furnaces. In addition to the one-atm experiments, experiments on implanted samples were also run at higher pressures (2.6 and 2.7 GPa) to assess the potential effects of pressure on He diffusion and the applicability of the measured diffusivities in describing He transport in the mantle. The high-pressure experiments were conducted in a piston-cylinder apparatus using an "ultra-soft" pressure cell, with the diffusion sample directly surrounded by AgCl. 3He distributions following experiments were measured with Nuclear Reaction Analysis using the reaction 3He(d,p)4He. This direct profiling method permits us to evaluate anisotropy of diffusion, which cannot be easily assessed using bulk-release methods. For diffusion in forsterite parallel to c we obtain the following Arrhenius relation over the temperatures 250-950°C: D = 3.91x10-6exp(-159 ± 4 kJ mol-1/RT) m2/sec. The data define a single Arrhenius line spanning more than 7 orders of magnitude in D and 700°C in temperature. Diffusion parallel to a appears slightly slower, yielding an activation energy for diffusion of 135 kJ/mol and a pre-exponential factor of 3.73x10-8 m2/sec. Diffusion parallel to b is slower than diffusion parallel to a (by about two-thirds of a log unit); for this orientation an activation energy of 138 kJ/mol and a pre-exponential factor of 1.34x10-8 m2/sec are obtained. This anisotropy is broadly consistent with observations for diffusion of Ni and Fe-Mg in olivine. Diffusion in Fe-bearing olivine (transport parallel to b) agrees within uncertainty with findings for He diffusion in forsterite. The higher-pressure experiments yield diffusivities in agreement with those from the 1-atm experiments, indicating that the results reported here can be reasonably applied to modeling He transport in the upper mantle. The insensitivity of He diffusion to pressure over the investigated range of conditions suggests that compression of the mineral lattice is not sufficient to significantly influence migration of the relatively small helium atoms, which likely diffuse via crystal interstices. The He diffusivities in this work are generally consistent with results from the study of Futagami et al. (1993), who measured He diffusion in natural olivine by outgassing 4He implanted samples, and with the diffusivities measured by bulk-release of 4He and 3He by Shuster et al. (2003), but are about 2 orders of magnitude slower than the recent findings of Tolstikhin et al. (2010) and Blard et al. (2008) . An up-temperature extrapolation of our data also show reasonable agreement with the higher-temperature measurements of Hart (1984). Blard et al. (2008) GCA 72, 3788-3803; Futagami et al. (1993) GCA 57, 3177-3194; Hart (1984) EPSL 70, 297-302; Shuster et al.( 2003) EPSL 217, 19-32; Tolstikhin et al. (2010) GCA 74, 1436-1447

Mercury speciation in brain tissue of polar bears (Ursus maritimus) from the Canadian Arctic.

PubMed

Krey, Anke; Kwan, Michael; Chan, Hing Man

2012-04-01

Methylmercury (MeHg) is a neurotoxicant that has been found at elevated concentrations in the Arctic ecosystem. Little is known about its internal dose in wildlife such as polar bears. We measured concentrations of mercury (Hg) in three different brain regions (cerebellum, frontal lobe and brain stem) of 24 polar bears collected from the Nunavik, Canada between 2000 and 2003. Speciation of Hg was measured by High Performance Liquid Chromatography coupled to Inductively Coupled Plasma Mass Spectroscopy (HPLC-ICP-MS). Concentrations of mean total Hg in brain tissue were up to 625 times lower (0.28 ± 0.07 mg kg(-1) dry weight (dw) in frontal lobe, 0.23 ± 0.07 mg kg(-1) dw in cerebellum and 0.12 ± 0.0 3mg kg(-1) dw in brain stem) than the mean total Hg concentration previously reported in polar bear liver collected from Eastern Baffin Island. Methylmercury (MeHg) accounted for 100% of the Hg found in all three brain regions analyzed. These results suggest that polar bear might reduce the toxic effects of Hg by limiting the uptake into the brain and/or decrease the rate of demethylation so that Hg can be excreted from the brain more easily. The toxicokinetics and the blood-brain-barrier mechanisms of polar bears are still unknown and further research is required. Copyright © 2012 Elsevier Inc. All rights reserved.

Coumafuryl (Fumarin) toxicity in chicks.

PubMed

Munger, L L; Su, J J; Barnes, H J

1993-01-01

Coumafuryl (Fumarin) toxicity was diagnosed in chickens less than 1 week of age. Mortality rate was 100%. Necropsy showed crops and gizzards to be full of feed. There was diffuse hemorrhage and unclotted blood in the abdomen and thorax. Histological examination showed congestion and hemorrhage. Chemical analysis of crop and gizzard contents contained approximately 340 ppm coumafuryl. The source of the coumafuryl was found to be the wood-straw mats in the chick boxes.

Select Small Core Structure Carbamates Exhibit High Contact Toxicity to “Carbamate-Resistant” Strain Malaria Mosquitoes, Anopheles gambiae (Akron)

PubMed Central

Wong, Dawn M.; Li, Jianyong; Chen, Qiao-Hong; Han, Qian; Mutunga, James M.; Wysinski, Ania; Anderson, Troy D.; Ding, Haizhen; Carpenetti, Tiffany L.; Verma, Astha; Islam, Rafique; Paulson, Sally L.; Lam, Polo C.-H.; Totrov, Maxim; Bloomquist, Jeffrey R.; Carlier, Paul R.

2012-01-01

Acetylcholinesterase (AChE) is a proven target for control of the malaria mosquito (Anopheles gambiae). Unfortunately, a single amino acid mutation (G119S) in An. gambiae AChE-1 (AgAChE) confers resistance to the AChE inhibitors currently approved by the World Health Organization for indoor residual spraying. In this report, we describe several carbamate inhibitors that potently inhibit G119S AgAChE and that are contact-toxic to carbamate-resistant An. gambiae. PCR-RFLP analysis was used to confirm that carbamate-susceptible G3 and carbamate-resistant Akron strains of An. gambiae carry wild-type (WT) and G119S AChE, respectively. G119S AgAChE was expressed and purified for the first time, and was shown to have only 3% of the turnover number (k cat) of the WT enzyme. Twelve carbamates were then assayed for inhibition of these enzymes. High resistance ratios (>2,500-fold) were observed for carbamates bearing a benzene ring core, consistent with the carbamate-resistant phenotype of the G119S enzyme. Interestingly, resistance ratios for two oxime methylcarbamates, and for five pyrazol-4-yl methylcarbamates were found to be much lower (4- to 65-fold). The toxicities of these carbamates to live G3 and Akron strain An. gambiae were determined. As expected from the enzyme resistance ratios, carbamates bearing a benzene ring core showed low toxicity to Akron strain An. gambiae (LC50>5,000 μg/mL). However, one oxime methylcarbamate (aldicarb) and five pyrazol-4-yl methylcarbamates (4a–e) showed good to excellent toxicity to the Akron strain (LC50 = 32–650 μg/mL). These results suggest that appropriately functionalized “small-core” carbamates could function as a resistance-breaking anticholinesterase insecticides against the malaria mosquito. PMID:23049714

Antitumor effect and toxicity of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles in mice bearing breast cancer.

PubMed

Carneiro, Marcella Lemos Brettas; Peixoto, Raphael C A; Joanitti, Graziela A; Oliveira, Ricardo G S; Telles, Luis A M; Miranda-Vilela, Ana L; Bocca, Anamélia L; Vianna, Leonora M S; da Silva, Izabel C R; de Souza, Aparecido R; Lacava, Zulmira G M; Báo, Sônia N

2013-02-16

Magnetic fluids containing superparamagnetic iron oxide nanoparticles represent an attractive platform as nanocarriers in chemotherapy. Recently, we developed a formulation of maghemite nanoparticles coated with rhodium (II) citrate, which resulted in in vitro cytotoxicity enhanced up to 4.6 times when compared to free rhodium (II) citrate formulation on breast carcinoma cells. In this work, we evaluate the antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Mice were evaluated with regard to the treatments' toxicity through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine; DNA fragmentation and cell cycle of bone marrow cells; and liver, kidney and lung histology. In addition, the antitumor activity of rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate was verified by tumor volume reduction, histology and immunohistochemistry. Regarding the treatments' toxicity, no experimental groups had alterations in levels of serum ALT or creatinine, and this suggestion was corroborated by the histopathologic examination of liver and kidney of mice. Moreover, DNA fragmentation frequency of bone marrow cells was lower than 15% in all experimental groups. On the other hand, the complexes rhodium (II) citrate-functionalized maghemite and free rhodium (II) citrate led to a marked growth inhibition of tumor and decrease in CD31 and Ki-67 staining. In summary, we demonstrated that both rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate formulations exhibited antitumor effects against 4T1 metastatic breast cancer cell line following intratumoral administration. This antitumor effect was followed by inhibition of both cell proliferation and microvascularization and by tumor tissue injury characterized as necrosis and fibrosis. Remarkably, this is the first published report demonstrating the therapeutic efficacy of maghemite nanoparticles coated with rhodium (II) citrate. This treatment prolonged the survival period of treated mice without inducing apparent systemic toxicity, which strengthens its use for future breast cancer therapeutic applications.

The in vitro respiratory toxicity of cristobalite-bearing volcanic ash.

PubMed

Damby, David E; Murphy, Fiona A; Horwell, Claire J; Raftis, Jennifer; Donaldson, Kenneth

2016-02-01

Ash from dome-forming volcanoes poses a unique hazard to millions of people worldwide due to an abundance of respirable cristobalite, a crystalline silica polymorph. Crystalline silica is an established respiratory hazard in other mixed dusts, but its toxicity strongly depends on sample provenance. Previous studies suggest that cristobalite-bearing volcanic ash is not as bio-reactive as may be expected for a dust containing crystalline silica. We systematically address the hazard posed by volcanic cristobalite by analysing a range of dome-related ash samples, and interpret the crystalline silica hazard according to the mineralogical nature of volcanic cristobalite. Samples are sourced from five well-characterized dome-forming volcanoes that span a range of magmatic compositions, specifically selecting samples rich in cristobalite (up to 16wt%). Isolated respirable fractions are used to investigate the in vitro response of THP-1 macrophages and A549 type II epithelial cells in cytotoxicity, cellular stress, and pro-inflammatory assays associated with crystalline silica toxicity. Dome-related ash is minimally reactive in vitro for a range of source compositions and cristobalite contents. Cristobalite-based toxicity is not evident in the assays employed, supporting the notion that crystalline silica provenance influences reactivity. Macrophages experienced minimal ash-induced cytotoxicity and intracellular reduction of glutathione; however, production of IL-1β, IL-6 and IL-8 were sample-dependent. Lung epithelial cells experienced moderate apoptosis, sample-dependent reduction of glutathione, and minimal cytokine production. We suggest that protracted interaction between particles and epithelial cells may never arise due to effective clearance by macrophages. However, volcanic ash has the propensity to incite a low, but significant, and sample-dependent response; the effect of this response in vivo is unknown and prolonged exposure may yet pose a hazard. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Antitumor effect of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles on mice bearing breast cancer: a systemic toxicity assay.

PubMed

Peixoto, Raphael Cândido Apolinário; Miranda-Vilela, Ana Luisa; de Souza Filho, José; Carneiro, Marcella Lemos' Brettas; Oliveira, Ricardo G S; da Silva, Matheus Oliveira; de Souza, Aparecido R; Báo, Sônia Nair

2015-05-01

Breast cancer is one of the most prevalent cancer types among women. The use of magnetic fluids for specific delivery of drugs represents an attractive platform for chemotherapy. In our previous studies, it was demonstrated that maghemite nanoparticles coated with rhodium (II) citrate (Magh-Rh2Cit) induced in vitro cytotoxicity and in vivo antitumor activity, followed by intratumoral administration in breast carcinoma cells. In this study, our aim was to follow intravenous treatment to evaluate the systemic antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Female Balb/c mice were evaluated with regard to toxicity of intravenous treatments through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine and liver, kidney, and lung histology. The antitumor activity of rhodium (II) citrate (Rh2Cit), Magh-Rh2Cit, and maghemite nanoparticles coated with citrate (Magh-Cit), used as control, was evaluated by tumor volume reduction, histology, and morphometric analysis. Magh-Rh2Cit and Magh-Cit promoted a significant decrease in tumor area, and no experimental groups presented hematotoxic effects or increased levels of serum ALT and creatinine. This observation was corroborated by the histopathological examination of the liver and kidney of mice. Furthermore, the presence of nanoparticles was verified in lung tissue with no morphological changes, supporting the idea that our nanoformulations did not induce toxicity effects. No studies about the systemic action of rhodium (II) citrate-loaded maghemite nanoparticles have been carried out, making this report a suitable starting point for exploring the therapeutic potential of these compounds in treating breast cancer.

Surface-to-volume ratio mapping of tumor microstructure using oscillating gradient diffusion weighted imaging

PubMed Central

Reynaud, Olivier; Winters, Kerryanne Veronica; Hoang, Dung Minh; Wadghiri, Youssef Zaim; Novikov, Dmitry S; Kim, Sungheon Gene

2015-01-01

Purpose To disentangle the free diffusivity (D0) and cellular membrane restrictions, via their surface-to-volume ratio (S/V), using the frequency-dependence of the diffusion coefficient D(ω), measured in brain tumors in the short diffusion-time regime using oscillating gradients (OGSE). Methods In vivo and ex vivo OGSE experiments were performed on mice bearing the GL261 murine glioma model (n=10) to identify the relevant time/frequency (t/ω) domain where D(ω) linearly decreases with ω−1/2. Parametric maps (S/V, D0) are compared to conventional DWI metrics. The impact of frequency range and temperature (20°C vs. 37°C) on S/V and D0 is investigated ex vivo. Results The validity of the short diffusion-time regime is demonstrated in vivo and ex vivo. Ex vivo measurements confirm that the purely geometric restrictions embodied in S/V are independent from temperature and frequency range, while the temperature dependence of the free diffusivity D0 is similar to that of pure water. Conclusion Our results suggest that D(ω) in the short diffusion-time regime can be used to uncouple the purely geometric restriction effect, such as S/V, from the intrinsic medium diffusivity properties, and provides a non-empirical and objective way to interpret frequency/time-dependent diffusion changes in tumors in terms of objective biophysical tissue parameters. PMID:26207354

Nuclear magnetic resonance diffusion pore imaging: Experimental phase detection by double diffusion encoding

NASA Astrophysics Data System (ADS)

Demberg, Kerstin; Laun, Frederik Bernd; Windschuh, Johannes; Umathum, Reiner; Bachert, Peter; Kuder, Tristan Anselm

2017-02-01

Diffusion pore imaging is an extension of diffusion-weighted nuclear magnetic resonance imaging enabling the direct measurement of the shape of arbitrarily formed, closed pores by probing diffusion restrictions using the motion of spin-bearing particles. Examples of such pores comprise cells in biological tissue or oil containing cavities in porous rocks. All pores contained in the measurement volume contribute to one reconstructed image, which reduces the problem of vanishing signal at increasing resolution present in conventional magnetic resonance imaging. It has been previously experimentally demonstrated that pore imaging using a combination of a long and a narrow magnetic field gradient pulse is feasible. In this work, an experimental verification is presented showing that pores can be imaged using short gradient pulses only. Experiments were carried out using hyperpolarized xenon gas in well-defined pores. The phase required for pore image reconstruction was retrieved from double diffusion encoded (DDE) measurements, while the magnitude could either be obtained from DDE signals or classical diffusion measurements with single encoding. The occurring image artifacts caused by restrictions of the gradient system, insufficient diffusion time, and by the phase reconstruction approach were investigated. Employing short gradient pulses only is advantageous compared to the initial long-narrow approach due to a more flexible sequence design when omitting the long gradient and due to faster convergence to the diffusion long-time limit, which may enable application to larger pores.

Diffusive Milli-Gels (DMG) for in situ assessment of metal bioavailability: A comparison with labile metal measurement using Chelex columns and acute toxicity to Ceriodaphnia dubia for copper in freshwaters.

PubMed

Perez, Magali; Simpson, Stuart L; Lespes, Gaëtane; King, Josh J; Adams, Merrin S; Jarolimek, Chad V; Grassl, Bruno; Schaumlöffel, Dirk

2016-12-01

Fluctuations in concentrations of bioavailable metals occur in most natural waters. In situ measurements are desirable to predict risks of adverse effects to aquatic organisms. We evaluated Diffusive Milli-Gels (DMG), a new in situ passive sampler, for assessing the bioavailability and toxicity of copper in waters exhibiting a wide range of characteristics. The performance was compared to an established Chelex-column method that measures labile copper concentrations by discrete sampling, and the ability to predict acute toxicity to the cladoceran, Ceriodaphnia dubia. The labile copper concentrations measured by the DMG and Chelex-column methods decreased with increasing dissolved organic carbon (DOC) (1.9-15 mg L -1 ) and hardness (21-270 mg CaCO 3  L -1 hardness), with 20-70% of total dissolved copper being present as labile copper. Toxicity decreased with increasing DOC and hardness. Strong linear relationships existed between the EC50 for C. dubia and DOC, and when the EC50 was related to either the labile copper concentrations measured by DMG (r 2  = 0.874) or the Chelex column (0.956) methods. The study demonstrates that the DMG passive sampler is a relevant tool for the in situ assessment of environmental risks posed by metals whose toxicity is strongly influenced by speciation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Color flow Doppler sonography for the etiologic diagnosis of thyrotoxicosis.

PubMed

Rosario, P W; Santos, J B N; Nunes, N S; da Silva, A L; Calsolari, M R

2014-06-01

The objective of this prospective study was to compare the results of color flow Doppler sonography (CFDS) and radioiodine scintigraphy in patients with thyrotoxicosis. A total of 176 patients, 102 with clinical thyrotoxicosis and 74 with subclinical dysfunction, were included. Pregnant and breast-feeding women, patients using amiodarone or recently exposed to iodinated contrast, and patients treated with antithyroid drugs were excluded. Total T3, free T4, TSH, and anti-TSH receptor antibodies were measured before scintigraphy and CFDS. Excluding one patient whose etiology of thyrotoxicosis remained undefined, CFDS showed 100% specificity. In fact, in all 10 cases in which scintigraphy and CFDS provided discordant results, the diagnosis suggested by the latter was correct. In patients with clinical thyrotoxicosis, the sensitivity of CFDS was 96% for diffuse toxic goiter, 95% for the absence of hyperfunction, and 100% for toxic nodular disease. In patients with subclinical dysfunction, the sensitivity of CFDS was 72.7% for diffuse toxic goiter, 90% for toxic adenoma, and 86.6% for toxic multinodular disease. CFDS was inconclusive in patients with parenchymal blood flow with patchy uneven distribution or with macronodules in which nodule vascularity compared to the remaining parenchyma did not permit to establish the diagnosis with certainty. CFDS can be used instead of scintigraphy not only in situations in which the latter is contraindicated or of limited value to define the etiology of thyrotoxicosis. © Georg Thieme Verlag KG Stuttgart · New York.

Orbital Transfer Rocket Engine Technology High Velocity Ratio Diffusing Crossover

DTIC Science & Technology

1992-12-01

The rotor was segmented into 10 weight groups and 25 finite elements. The bearings were represented as translational springs to ground ( rigid casing...personnel: Advanced Rotating Machinery: Mr. Robert Sutton Mr. Tim Irvin Mr. Hal Buddenbohm Mr. A] Uttle Fluid Dynamics : Dr. Eugene Jackson Mr. Anthony...1 7 Dynamic Soft Wear Ring Seals ................................... #,.................so

Solar-Assisted Oxidation of Toxic Cyanide

NASA Technical Reports Server (NTRS)

Byvik, C. E.; Miles, A.

1985-01-01

In solar-assisted oxidation technique, oxygen-bearing air bubbled through cyanide solution in which platinized powdered TiO2 is suspended. Light from either artifical source or natural Sunlight irradiates. Experiments demonstrated this technique effective in reducing concentration of cyanide to levels well below those achieved by other methods. Results suggest effective and inexpensive method for oxidizing cyanide in industrial wastewaters.

Comparison of Steady State Evaporation Models for Toxic Chemical Spills: Development of a New Evaporation Model

DTIC Science & Technology

1989-11-29

for diffusivity based on theory : DVab- 0.002e6 703/2 eS/s(bPM11 t/ ,cm/s (28) ab ab 1) where DV-b a molecular diffusion coefflcient of chemical a In...24 Ugt W m -K (48)S[(/hg) + (1/h)] m- K- where ha is the coefficient of heat conduction through the ground, and hl is the liquid heat transfer

Idea Bank.

ERIC Educational Resources Information Center

Talesnick, Irwin, Ed.

1983-01-01

Describes experiments on diffusion of gases, volumetric approach to water of hydration, and toxicity of chemicals in the laboratory. Also describes an inexpensive automatic pipette, overhead projection of chemical reactions, and an alternative method for demonstrating flame tests. (JN)

Modeling Biogeochemical Cycling of Heavy Metals in Lake Coeur d'Alene Sediments

NASA Astrophysics Data System (ADS)

Sengor, S. S.; Spycher, N.; Belding, E.; Curthoys, K.; Ginn, T. R.

2005-12-01

Mining of precious metals since the late 1800's have left Lake Coeur d'Alene (LCdA) sediments heavily enriched with toxic metals, including Cd, Cu, Pb, and Zn. Indigenous microbes however are capable of catalyzing reactions that detoxify the benthic and aqueous lake environments, and thus constitute an important driving component in the biogeochemical cycles of these metals. Here we report on the development of a quantitative model of transport, fate, exposure and effects of toxic compounds on benthic microbial communities at LCdA. First, chemical data from the LCdA area have been compiled from multiple sources to investigate trends in chemical occurrence, as well as to define model boundary conditions. The model is structured as 1-D diffusive reactive transport model to simulate spatial and temporal distribution of metals through the benthic sediments. Inorganic reaction processes included in the model are aqueous speciation, surface complexation, mineral precipitation/dissolution and abiotic redox reactions. Simulations with and without surface complexation are carried out to evaluate the effect of sorption and the conservative behaviour of metals within the benthic sediments under abiotic and purely diffusive transport. The 1-D inorganic diffusive transport model is then coupled to a biotic reaction network including consortium biodegradation kinetics with multiple electron acceptors, product toxicity, and energy partitioning. Multiyear simulations are performed, with water column chemistry established as a boundary condition from extant data, to explore the role of biogeochemical dynamics on benthic fluxes of metals in the long term.

Optothermal in vitro diffusion measurements through silicone membranes

NASA Astrophysics Data System (ADS)

Cowen, J. A.; Liu, H.; Xiao, P.; Imhof, R. E.

2003-01-01

We report the development of a new method for measuring diffusion rates of surface-applied chemicals through polymer membranes such as polydimethylsiloxane (PDMS). An important feature of the approach is the use of optothermal transient emission radiometry to sense diffusant concentration in a noncontacting, noninvasive way. This allows the method to be adapted to perform similar measurements on human skin in vivo, thus providing a way of cross-verifying in vivo and in vitro measurements. The correlation between in vitro and in vivo diffusion measurements is also important for developing credible alternatives to in vivo testing, for use with toxic chemicals or animal substitution. We present the results of experiments with several polyols diffusing through PDMS membranes of thickness 125 or 250 μm, describing the experimental details, the measurement protocol, the data analysis methods, and a study of measurement errors.

Blood Pump Bearing System

NASA Technical Reports Server (NTRS)

Aber, Gregory S. (Inventor)

1999-01-01

Methods and apparatus are provided for a blood pump bearing system within a pump housing to support long-term high-speed rotation of a rotor with an impeller blade having a plurality of individual magnets disposed thereon to provide a small radial air gap between the magnets and a stator of less than 0.025 inches. The bearing system may be mounted within a flow straightener, diffuser, or other pump element to support the shaft of a pump rotor. The bearing system includes a zirconia shaft having a radiused end. The radiused end has a first radius selected to be about three times greater than the radius of the zirconia shaft. The radiused end of the zirconia shaft engages a flat sapphire endstone. Due to the relative hardness of these materials a flat is quickly produced during break-in on the zirconia radiused end of precisely the size necessary to support thrust loads whereupon wear substantially ceases. Due to the selection of the first radius, the change in shaft end-play during pump break-in is limited to a total desired end-play of less than about 0.010 inches. Radial loads are supported by an olive hole ring jewel that makes near line contact around the circumference of the shaft to support high speed rotation with little friction. The width of olive hole ring jewel is small to allow heat to conduct through to thereby prevent heat build-up in the bearing. A void defined by the bearing elements may fill with blood that then coagulates within the void. The coagulated blood is then conformed to the shape of the bearing surfaces.

Blood Pump Bearing System

NASA Technical Reports Server (NTRS)

Aber, Gregory S. (Inventor)

2000-01-01

An apparatus is provided for a blood pump bearing system within a pump housing to support long-term highspeed rotation of a rotor with an impeller blade having a plurality of individual magnets disposed thereon to provide a small radial air gap between the magnets and a stator of less than 0.025 inches. The bearing system may be mounted within a flow straightener, diffuser, or other pump element to support the shaft of a pump rotor. The bearing system includes a zirconia shaft having a radiused end. The radiused end has a first radius selected to be about three times greater than the radius of the zirconia shaft. The radiused end of the zirconia shaft engages a flat sapphire endstone. Due to the relative hardness of these materials a flat is quickly produced during break-in on the zirconia radiused end of precisely the size necessary to support thrust loads whereupon wear substantially ceases. Due to the selection of the first radius, the change in shaft end-play during pump break-in is limited to a total desired end-play of less than about 0.010 inches. Radial loads are supported by an olive hole ring jewel that makes near line contact around the circumference of the Ir shaft to support big speed rotation with little friction. The width of olive hole ring jewel is small to allow heat to conduct through to thereby prevent heat build-up in the bearing. A void defined by the bearing elements may fill with blood that then coagulates within the void. The coagulated blood is then conformed to the shape of the bearing surfaces.

Effects of hurricanes Katrina and Rita on Louisiana black bear habitat

USGS Publications Warehouse

Clark, Joseph D.; Murrow, Jennifer L.

2012-01-01

The Louisiana black bear (Ursus americanus luteolus) is comprised of 3 subpopulations, each being small, geographically isolated, and vulnerable to extinction. Hurricanes Katrina and Rita struck the Louisiana and Mississippi coasts in 2005, potentially altering habitat occupied by this federally threatened subspecies. We used data collected on radio-telemetered bears from 1993 to 1995 and pre-hurricane landscape data to develop a habitat model based on the Mahalanobis distance (D2) statistic. We then applied that model to post-hurricane landscape data where the telemetry data were collected (i.e., occupied study area) and where bear range expansion might occur (i.e., unoccupied study area) to quantify habitat loss or gain. The D2 model indicated that quality bear habitat was associated with areas of high mast-producing forest density, low water body density, and moderate forest patchiness. Cross-validation and testing on an independent data set in central Louisiana indicated that prediction and transferability of the model were good. Suitable bear habitat decreased from 348 to 345 km2 (0.9%) within the occupied study area and decreased from 34,383 to 33,891 km2 (1.4%) in the unoccupied study area following the hurricanes. Our analysis indicated that bear habitat was not significantly degraded by the hurricanes, although changes that could have occurred on a microhabitat level would be more difficult to detect at the resolution we used. We suggest that managers continue to monitor the possible long-term effects of these hurricanes (e.g., vegetation changes from flooding, introduction of toxic chemicals, or water quality changes).

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

Southworth, G.R.; Loar, J.M.; Ryon, M.G.

Ecological studies of the Bear Creek watershed, which drains the area surrounding several Oak Ridge Y-12 Plant waste disposal facilities, were initiated in May 1984 and are continuing at present. These studies consisted of an initial, detailed characterization of the benthic invertebrate and fish communities in Bear Creek, and they were followed by a presently ongoing monitoring phase that involves reduced sampling intensities. The characterization phase utilized two approaches: (1) instream sampling of benthic invertebrate and fish communities in Bear Creek to identify spatial and temporal patterns in distribution and abundance and (2) laboratory bioassays on water samples from Bearmore » Creek and selected tributaries to identify potential sources of toxicity to biota. The monitoring phase of the ecological program relates to the long-term goals of identifying and prioritizing contaminant sources and assessing the effectiveness of remedial actions. It continues activities of the characterization phase at less frequent intervals. The Bear Greek Valley is a watershed that drains the area surrounding several closed Oak Ridge Y-12 Plant waste disposal facilities. Past waste disposal practices in Bear Creek Valley resulted in contamination of Bear Creek and consequent ecological damage. Extensive remedial actions have been proposed at waste sites, and some of the have been implemented or are now underway. The proposed study plan consists of an initial, detailed characterization of the benthic invertebrate and fish communities in Bear Creek in the first year followed by a reduction in sampling intensity during the monitoring phase of the plan. The results of sampling conducted from May 1984 through early 1989 are presented in this report.« less

Śodhana: An Ayurvedic process for detoxification and modification of therapeutic activities of poisonous medicinal plants

PubMed Central

Maurya, Santosh Kumar; Seth, Ankit; Laloo, Damiki; Singh, Narendra Kumar; Gautam, Dev Nath Singh; Singh, Anil Kumar

2015-01-01

Ayurveda involves the use of drugs obtained from plants, animals, and mineral origin. All the three sources of drugs can be divided under poisonous and nonpoisonous category. There are various crude drugs, which generally possess unwanted impurities and toxic substances, which can lead to harmful health problems. Many authors have reported that not all medicinal plants are safe to use since they can bear many toxic and harmful phytoconstituents in them. Śodhana (detoxification/purification) is the process, which involves the conversion of any poisonous drug into beneficial, nonpoisonous/nontoxic ones. Vatsanābha (Aconitum species), Semecarpus anacardium, Strychnos nux-vomica, Acorus calamus, Abrus precatorius etc., are some of the interesting examples of toxic plants, which are still used in the Indian system of medicine. Aconite, bhilawanols, strychnine, β–asarone, abrin are some of the toxic components present in these plants and are relatively toxic in nature. Śodhana process involves the purification as well as reduction in the levels of toxic principles which sometimes results in an enhanced therapeutic efficacy. The present review is designed to extensively discuss and understand the scientific basis of the alternative use of toxic plants as a medicine after their purification process. PMID:26283803

Ternary copper(II) complex: NCI60 screening, toxicity studies, and evaluation of efficacy in xenograft models of nasopharyngeal carcinoma.

PubMed

Ahmad, Munirah; Suhaimi, Shazlan-Noor; Chu, Tai-Lin; Abdul Aziz, Norazlin; Mohd Kornain, Noor-Kaslina; Samiulla, D S; Lo, Kwok-Wai; Ng, Chew-Hee; Khoo, Alan Soo-Beng

2018-01-01

Copper(II) ternary complex, [Cu(phen)(C-dmg)(H2O)]NO3 was evaluated against a panel of cell lines, tested for in vivo efficacy in nasopharyngeal carcinoma xenograft models as well as for toxicity in NOD scid gamma mice. The Cu(II) complex displayed broad spectrum cytotoxicity against multiple cancer types, including lung, colon, central nervous system, melanoma, ovarian, and prostate cancer cell lines in the NCI-60 panel. The Cu(II) complex did not cause significant induction of cytochrome P450 (CYP) 3A and 1A enzymes but moderately inhibited CYP isoforms 1A2, 2C9, 2C19, 2D6, 2B6, 2C8 and 3A4. The complex significantly inhibited tumor growth in nasopharyngeal carcinoma xenograft bearing mice models at doses which were well tolerated without causing significant or permanent toxic side effects. However, higher doses which resulted in better inhibition of tumor growth also resulted in toxicity.

Potential anthelmintics: polyphenols from the tea plant Camellia sinensis L. are lethally toxic to Caenorhabditis elegans.

PubMed

Mukai, Daisuke; Matsuda, Noriko; Yoshioka, Yu; Sato, Masashi; Yamasaki, Toru

2008-04-01

A novel gallate of tannin, (-)-epigallocatechin-(2 beta-->O-->7',4 beta-->8')-epicatechin-3'-O-gallate (8), together with (-)-epicatechin-3-O-gallate (4), (-)-epigallocatechin (5), (-)-epigallocatechin-3-O-gallate (6), and (+)-gallocatechin-(4 alpha-->8')-epigallocatechin (7), were isolated from the tea plant Camellia sinensis (L.) O. Kuntze var. sinensis (cv., Yabukita). The structure of 8, including stereochemistry, was elucidated by spectroscopic methods and hydrolysis. The compounds, along with commercially available pyrogallol (1), (+)-catechin (2), and (-)-epicatechin (3), were examined for toxicity towards egg-bearing adults of Caenorhabditis elegans. The anthelmintic mebendazole (9) was used as a positive control. Neither 2 nor 3 were toxic but the other compounds were toxic in the descending order 8, 7 approximately 6, 9, 4, 5, 1. The LC(50) (96 h) values of 8 and 9 were evaluated as 49 and 334 micromol L(-1), respectively. These data show that many green tea polyphenols may be potential anthelmintics.

Cobalt toxicity after revision total hip replacement due to fracture of a ceramic head.

PubMed

Pelayo-de Tomás, J M; Novoa-Parra, C; Gómez-Barbero, P

Symptomatic cobalt toxicity from a failed total hip replacement is a rare, but devastating complication. Potential clinical findings include cardiomyopathy, hypothyroidism, skin rash, visual and hearing impairment, polycythaemia, weakness, fatigue, cognitive impairment, and neuropathy. The case is presented of a 74year-old man in whom, after a ceramic-ceramic replacement and two episodes of prosthetic dislocation, it was decided to replace it with a polyethylene-metal total hip arthroplasty (THA). At 6months after the revision he developed symptoms of cobalt toxicity, confirmed by analytical determination (serum cobalt level=651.2μg/L). After removal of the prosthesis, the levels of chromium and cobalt in blood and urine returned to normal, with the patient currently being asymptomatic. It is recommended to use a new ceramic on ceramic bearing at revision, in order to minimise the risk of wear-related cobalt toxicity following breakage of ceramic components. Copyright © 2016 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

Cationized gelatin-HVJ envelope with sodium borocaptate improved the BNCT efficacy for liver tumors in vivo

PubMed Central

2011-01-01

Background Boron neutron capture therapy (BNCT) is a cell-selective radiation therapy that uses the alpha particles and lithium nuclei produced by the boron neutron capture reaction. BNCT is a relatively safe tool for treating multiple or diffuse malignant tumors with little injury to normal tissue. The success or failure of BNCT depends upon the 10B compound accumulation within tumor cells and the proximity of the tumor cells to the body surface. To extend the therapeutic use of BNCT from surface tumors to visceral tumors will require 10B compounds that accumulate strongly in tumor cells without significant accumulation in normal cells, and an appropriate delivery method for deeper tissues. Hemagglutinating Virus of Japan Envelope (HVJ-E) is used as a vehicle for gene delivery because of its high ability to fuse with cells. However, its strong hemagglutination activity makes HVJ-E unsuitable for systemic administration. In this study, we developed a novel vector for 10B (sodium borocaptate: BSH) delivery using HVJ-E and cationized gelatin for treating multiple liver tumors with BNCT without severe adverse events. Methods We developed cationized gelatin conjugate HVJ-E combined with BSH (CG-HVJ-E-BSH), and evaluated its characteristics (toxicity, affinity for tumor cells, accumulation and retention in tumor cells, boron-carrying capacity to multiple liver tumors in vivo, and bio-distribution) and effectiveness in BNCT therapy in a murine model of multiple liver tumors. Results CG-HVJ-E reduced hemagglutination activity by half and was significantly less toxic in mice than HVJ-E. Higher 10B concentrations in murine osteosarcoma cells (LM8G5) were achieved with CG-HVJ-E-BSH than with BSH. When administered into mice bearing multiple LM8G5 liver tumors, the tumor/normal liver ratios of CG-HVJ-E-BSH were significantly higher than those of BSH for the first 48 hours (p < 0.05). In suppressing the spread of tumor cells in mice, BNCT treatment was as effective with CG-HVJ-E-BSH as with BSH containing a 35-fold higher 10B dose. Furthermore, CG-HVJ-E-BSH significantly increased the survival time of tumor-bearing mice compared to BSH at a comparable dosage of 10B. Conclusion CG-HVJ-E-BSH is a promising strategy for the BNCT treatment of visceral tumors without severe adverse events to surrounding normal tissues. PMID:21247507

Accumulation, internalization and therapeutic efficacy of neuropilin-1-targeted liposomes

PubMed Central

Paoli, Eric E.; Ingham, Elizabeth S.; Zhang, Hua; Mahakian, Lisa M.; Fite, Brett Z.; Gagnon, M. Karen; Tam, Sarah; Kheirolomoom, Azadeh; Cardiff, Robert D.; Ferrara, Katherine W.

2014-01-01

Advancements in liposomal drug delivery have produced long circulating and very stable drug formulations. These formulations minimize systemic exposure; however, unfortunately, therapeutic efficacy has remained limited due to the slow diffusion of liposomal particles within the tumor and limited release or uptake of the encapsulated drug. Here, the carboxyl-terminated CRPPR peptide, with affinity for the receptor neuropilin-1 (NRP), which is expressed on both endothelial and cancer cells, was conjugated to liposomes to enhance the tumor accumulation. Using a pH sensitive probe, liposomes were optimized for specific NRP binding and subsequent cellular internalization using in vitro cellular assays. Liposomes conjugated with the carboxyl-terminated CRPPR peptide (termed C-LPP liposomes) bound to the NRP-positive primary prostatic carcinoma cell line (PPC-1) but did not bind to the NRP-negative PC-3 cell line, and binding was observed with liposomal peptide concentrations as low as 0.16 mol%. Binding of the C-LPP liposomes was receptor-limited, with saturation observed at high liposome concentrations. The identical peptide sequence bearing an amide terminus did not bind specifically, accumulating only with a high (2.5 mol%) peptide concentration and adhering equally to NRP positive and negative cell lines. The binding of C-LPP liposomes conjugated with 0.63 mol% of the peptide was 83-fold greater than liposomes conjugated with the amide version of the peptide. Cellular internalization was also enhanced with C-LPP liposomes, with 80% internalized following 3hr incubation. Additionally, fluorescence in the blood pool (~40% of the injected dose) was similar for liposomes conjugated with 0.63 mol% of carboxyl-terminated peptide and non-targeted liposomes at 24 hr after injection, indicating stable circulation. Prior to doxorubicin treatment, in vivo tumor accumulation and vascular targeting were increased for peptide-conjugated liposomes compared to non-targeted liposomes based on confocal imaging of a fluorescent cargo, and the availability of the vascular receptor was confirmed with ultrasound molecular imaging. Finally, over a 4-week course of therapy, tumor knockdown resulting from doxorubicin-loaded, C-LPP liposomes was similar to non-targeted liposomes in syngeneic tumor-bearing FVB mice and C-LPP liposomes reduced doxorubicin accumulation in the skin and heart and eliminated skin toxicity. Taken together, our results demonstrate that a carboxyl-terminated RXXR peptide sequence, conjugated to liposomes at a concentration of 0.63 mol%, retains long circulation but enhances binding and internalization, and reduces toxicity. PMID:24434424

Protein Corona Formation on Colloidal Polymeric Nanoparticles and Polymeric Nanogels: Impact on Cellular Uptake, Toxicity, Immunogenicity, and Drug Release Properties.

PubMed

Obst, Katja; Yealland, Guy; Balzus, Benjamin; Miceli, Enrico; Dimde, Mathias; Weise, Christoph; Eravci, Murat; Bodmeier, Roland; Haag, Rainer; Calderón, Marcelo; Charbaji, Nada; Hedtrich, Sarah

2017-06-12

The adsorption of biomolecules to the surface of nanoparticles (NPs) following administration into biological environments is widely recognized. In particular, the "protein corona" is well understood in terms of formation kinetics and impact upon the biological interactions of NPs. Its presence is an essential consideration in the design of therapeutic NPs. In the present study, the protein coronas of six polymeric nanoparticles of prospective therapeutic use were investigated. These included three colloidal NPs-soft core-multishell (CMS) NPs, plus solid cationic Eudragit RS (EGRS), and anionic ethyl cellulose (EC) nanoparticles-and three nanogels (NGs)-thermoresponsive dendritic-polyglycerol (dPG) nanogels (NGs) and two amino-functionalized dPG-NGs. Following incubation with human plasma, protein coronas were characterized and their biological interactions compared with pristine NPs. All NPs demonstrated protein adsorption and increased hydrodynamic diameters, although the solid EGRS and EC NPs bound notably more protein than the other tested particles. Shifts toward moderately negative surface charges were also observed for all corona bearing NPs, despite varied zeta potentials in their pristine states. While the uptake and cellular adhesion of the colloidal NPs in primary human keratinocytes and human umbilical vein endothelial cells were significantly decreased when bearing the protein corona, no obvious impact was seen in the NGs. By contrast, corona bearing NGs induced marked increases in cytokine release from primary human macrophages not seen with corona bearing colloidal NPs. Despite this, no apparent enhancement to in vitro toxicity was noted. Finally, drug release from EGRS and EC NPs was assessed, where a decrease was seen in the EGRS NPs alone. Together these results provide a direct comparison of the physical and biological impact the protein corona has on NPs of widely varied character and in particular highlights a distinction between the corona's effects on NGs and colloidal NPs.

Assessment of neurotoxic effects of mercury in beluga whales (Delphinapterus leucas), ringed seals (Pusa hispida), and polar bears (Ursus maritimus) from the Canadian Arctic.

PubMed

Krey, Anke; Ostertag, Sonja K; Chan, Hing Man

2015-03-15

Marine mammals are indicator species of the Arctic ecosystem and an integral component of the traditional Inuit diet. The potential neurotoxic effects of increased mercury (Hg) in beluga whales (Delphinapterus leucas), ringed seals (Pusa hispida), and polar bears (Ursus maritimus) are not clear. We assessed the risk of Hg-associated neurotoxicity to these species by comparing their brain Hg concentrations with threshold concentrations for toxic endpoints detected in laboratory animals and field observations: clinical symptoms (>6.75 mg/kg wet weight (ww)), neuropathological signs (>4 mg/kg ww), neurochemical changes (>0.4 mg/kg ww), and neurobehavioral changes (>0.1mg/kg ww). The total Hg (THg) concentrations in the cerebellum and frontal lobe of ringed seals and polar bears were <0.5mg/kg ww, whereas the average concentration in beluga whale brain was >3mg/kg ww. Our results suggest that brain THg levels in polar bears are below levels that induce neurobehavioral effects as reported in the literature, while THg concentrations in ringed seals are within the range that elicit neurobehavioral effects and individual ringed seals exceed the threshold for neurochemical changes. The relatively high THg concentration in beluga whales exceeds all of the neurotoxicity thresholds assessed. High brain selenium (Se):Hg molar ratios were observed in all three species, suggesting that Se could protect the animals from Hg-associated neurotoxicity. This assessment was limited by several factors that influence neurotoxic effects in animals, including: animal species; form of Hg in the brain; and interactions with modifiers of Hg-associated toxicity, such as Se. Comparing brain Hg concentrations in wildlife with concentrations of appropriate laboratory studies can be used as a tool for risk characterization of the neurotoxic effects of Hg in Arctic marine mammals. Copyright © 2014 Elsevier B.V. All rights reserved.

Toxic shock syndrome in two dogs.

PubMed

Slovak, Jennifer E; Parker, Valerie J; Deitz, Krysta L

2012-01-01

Two young, unrelated, spayed female Labrador retrievers were evaluated for severe, diffuse, generalized erythema and edema of the skin. Both dogs exhibited signs of disseminated intravascular coagulopathy and were euthanized. On postmortem examination, toxic shock syndrome (TSS) was diagnosed based on histopathology and supported by skin cultures. TSS is a rarely reported disease in veterinary medicine and can cause acute and profound clinical signs. Rapid recognition of this disease process and immediate treatment may improve the clinical outcome.

Superconducting Meissner Effect Bearings for Cryogenic Turbomachines. Phase 1

DTIC Science & Technology

1989-05-01

May 18 16 SUPPLEMENTARY NOTATION I? COSAr ICODES I. SUBJECT TERMS (Continue oan reverse if nocesnay and identify by block number) FIELD GROUP SUB...EXTERNAL FIELD FOR TYPE I AND TYPE II SUPERCONDUCTORS ........................................... 9 2.2 FIELD FROM A PERMANENT MAGNET THROUGH A TYPE II...OF TURBOEXPANDER........................ 33 4.2 TURBINE ROTOR , NOZZLES AND DIFFUSER PARAMETERS ..................... 34 5.1 SPACECRAFT PERIODIC

Cytotoxic effects of denture adhesives on primary human oral keratinocytes, fibroblasts and permanent L929 cell lines.

PubMed

Chen, Fengying; Wu, Tianfu; Cheng, Xiangrong

2014-03-01

To date, there have been very little data on the cytotoxic responses of different cell lines to denture adhesives. To determine the cytotoxicity of three denture adhesives on primary human oral keratinocytes (HOKs), fibroblasts (HOFs) and permanent mouse fibroblasts cell lines (L929). Three commercial denture adhesives (two creams and one powder) were prepared for indirect contact using the agar diffusion test, as well as extracts in MTT assay. The results of the MTT assay were statistically analysed by one-way anova and Tukey's test (p < 0.05). All of the tested denture adhesives showed mild to moderate cytotoxicity to primary HOKs (p < 0.001), whereas none of three was toxic to L929 cells (p > 0.05) in both assays. For primary HOFs cultures, slight cytotoxicity was observed for one of the products from the agar diffusion test and undiluted eluates of all tested adhesives with MTT assay (p < 0.01). Denture adhesives are toxic to the primary HOKs and HOFs cultures, whereas non-toxic to L929 cells. The results suggest that primary human oral mucosal cells may provide more valuable information in toxicity screening of denture adhesives. © 2012 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.

Effect of Plasma Nitriding and Nitrocarburizing on HVOF-Sprayed Stainless Steel Coatings

NASA Astrophysics Data System (ADS)

Park, Gayoung; Bae, Gyuyeol; Moon, Kyungil; Lee, Changhee

2013-12-01

In this work, the effects of plasma nitriding (PN) and nitrocarburizing on HVOF-sprayed stainless steel nitride layers were investigated. 316 (austenitic), 17-4PH (precipitation hardening), and 410 (martensitic) stainless steels were plasma-nitrided and nitrocarburized using a N2 + H2 gas mixture and the gas mixture containing C2H2, respectively, at 550 °C. The results showed that the PN and nitrocarburizing produced a relatively thick nitrided layer consisting of a compound layer and an adjacent nitrogen diffusion layer depending on the crystal structures of the HVOF-sprayed stainless steel coatings. Also, the diffusion depth of nitrogen increased when a small amount of C2H2 (plasma nitrocarburizing process) was added. The PN and nitrocarburizing resulted in not only an increase of the surface hardness, but also improvement of the load bearing capacity of the HVOF-sprayed stainless steel coatings because of the formation of CrN, Fe3N, and Fe4N phases. Also, the plasma-nitrocarburized HVOF-sprayed 410 stainless steel had a superior surface microhardness and load bearing capacity due to the formation of Cr23C6 on the surface.

Enhancing curcumin anticancer efficacy through di-block copolymer micelle encapsulation.

PubMed

Lv, Li; Shen, Yuanyuan; Liu, Jieying; Wang, Feihu; Li, Min; Li, Min; Guo, Aijie; Wang, Yun; Zhou, Dejian; Guo, Shengrong

2014-02-01

We report herein the development of a novel aqueous formulation and improved antitumor activity for curcumin by encapsulating it into a biocompatible and biodegradable poly(L-lactic acid) based poly(anhydride-ester)-b-poly(ethylene glycol) (PAE-b-PEG) micelle. The resulting curcumin loaded micelles were completely water-dispersible, overcoming the problem of poor water solubility that limited its efficacy and bioavailability. In vitro cellular studies revealed that the curcumin-loaded micelles were taken up mainly via endocytosis route and exhibited higher cytotoxicities toward model cancer cell lines (HeLa and EMT6) than free curcumin. An in vivo biodistribution study revealed that the curcumin-loaded micelles displayed significantly enhanced accumulation inside the tumor of EMT6 breast tumor-bearing mice. More impressively, the curcumin-loaded micelles showed stronger antitumor activity, higher anti-angiogenesis effects and induced apoptosis on the EMT6 breast tumor model bearing mice than free curcumin. Furthermore, the curcumin-loaded micelles showed no significant toxicity towards hemotological system, major organs or tissues in mice. Combined with a high antitumor activity and low toxic side-effects, the curcumin-loaded micelles developed here thus appear to be a highly attractive nanomedicine for effective, targeted cancer therapy.

Differences in mercury bioaccumulation between polar bears (Ursus maritimus) from the Canadian high- and sub-Arctic.

PubMed

St Louis, Vincent L; Derocher, Andrew E; Stirling, Ian; Graydon, Jennifer A; Lee, Caroline; Jocksch, Erin; Richardson, Evan; Ghorpade, Sarah; Kwan, Alvin K; Kirk, Jane L; Lehnherr, Igor; Swanson, Heidi K

2011-07-15

Polar bears (Ursus maritimus) are being impacted by climate change and increased exposure to pollutants throughout their northern circumpolar range. In this study, we quantified concentrations of total mercury (THg) in the hair of polar bears from Canadian high- (southern Beaufort Sea, SBS) and sub- (western Hudson Bay, WHB) Arctic populations. Concentrations of THg in polar bears from the SBS population (14.8 ± 6.6 μg g(-1)) were significantly higher than in polar bears from WHB (4.1 ± 1.0 μg g(-1)). On the basis of δ(15)N signatures in hair, in conjunction with published δ(15)N signatures in particulate organic matter and sediments, we estimated that the pelagic and benthic food webs in the SBS are ∼ 4.7 and ∼ 4.0 trophic levels long, whereas in WHB they are only ∼ 3.6 and ∼ 3.3 trophic levels long. Furthermore, the more depleted δ(13)C ratios in hair from SBS polar bears relative to those from WHB suggests that SBS polar bears feed on food webs that are relatively more pelagic (and longer), whereas polar bears from WHB feed on those that are relatively more benthic (and shorter). Food web length and structure accounted for ∼ 67% of the variation we found in THg concentrations among all polar bears across both populations. The regional difference in polar bear hair THg concentrations was also likely due to regional differences in water-column concentrations of methyl Hg (the toxic form of Hg that biomagnifies through food webs) available for bioaccumulation at the base of the food webs. For example, concentrations of methylated Hg at mid-depths in the marine water column of the northern Canadian Arctic Archipelago were 79.8 ± 37.3 pg L(-1), whereas, in HB, they averaged only 38.3 ± 16.6 pg L(-1). We conclude that a longer food web and higher pelagic concentrations of methylated Hg available to initiate bioaccumulation in the BS resulted in higher concentrations of THg in polar bears from the SBS region compared to those inhabiting the western coast of HB.

Novel Fabric Containing Microcapsules of Chemical Decontaminants Encapsulated within Semipermeable Polymers.

DTIC Science & Technology

The invention concerns novel clothing fabrics containing microcapsules in a resin finish comprising reactive chemical decontamination agents...allowing the toxic chemicals to diffuse into the microcapsules where they undergo irreversible detoxifying chemical reactions.

Cyanide does more to inhibit heme enzymes, than merely serving as an active-site ligand

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

Parashar, Abhinav; Venkatachalam, Avanthika; Gideon, Daniel Andrew

Highlights: • Cyanide (CN) is a well-studied toxic principle, known to inhibit heme-enzymes. • Inhibition is supposed to result from CN binding at the active site as a ligand. • Diverse heme enzymes’ CN inhibition profiles challenge prevailing mechanism. • Poor binding efficiency of CN at low enzyme concentrations and ligand pressures. • CN-based diffusible radicals cause ‘non-productive electron transfers’ (inhibition). - Abstract: The toxicity of cyanide is hitherto attributed to its ability to bind to heme proteins’ active site and thereby inhibit their activity. It is shown herein that the long-held interpretation is inadequate to explain several observations inmore » heme-enzyme reaction systems. Generation of cyanide-based diffusible radicals in heme-enzyme reaction milieu could shunt electron transfers (by non-active site processes), and thus be detrimental to the efficiency of oxidative outcomes.« less

Chemotherapeutic potential of curcumin-bearing microcells against hepatocellular carcinoma in model animals

PubMed Central

Farazuddin, Mohammad; Dua, Bhavyata; Zia, Qamar; Khan, Aijaz Ahmad; Joshi, Beenu; Owais, Mohammad

2014-01-01

Curcumin (diferuloylmethane) is found in large quantities in the roots of Curcuma longa. It possesses strong antioxidant and anti-inflammatory properties, and inhibits chemically-induced carcinogenesis in the skin, forestomach, colon, and liver. Unfortunately, the poor bioavailability and hydrophobicity of curcumin pose a major hurdle to its use as a potent anticancer agent. To circumvent some of these problems, we developed a novel, dual-core microcell formulation of curcumin. The encapsulation of curcumin in microcells increases its solubility and bioavailability, and facilitates slow release kinetics over extended periods. Besides being safe, these formulations do not bear any toxicity constraints, as revealed by in vitro and in vivo studies. Histopathological analysis revealed that curcumin-bearing microcells helped in regression of hepatocellular carcinoma and the maintenance of cellular architecture in liver tissue. Free curcumin had a very mild effect on cancer suppression. Empty (sham) microcells and microparticles failed to inhibit cancer cells. The novel curcumin formulation was found to suppress hepatocellular carcinoma efficiently in Swiss albino mice. PMID:24627632

The Measurement of Thermal Diffusivity in Conductor and Insulator by Photodeflection Technique

NASA Astrophysics Data System (ADS)

Achathongsuk, U.; Rittidach, T.; Tipmonta, P.; Kijamnajsuk, P.; Chotikaprakhan, S.

2017-09-01

The purpose of this study is to estimate thermal diffusivities of high thermal diffusivity bulk material as well as low thermal diffusivity bulk material by using many types of fluid such as Ethyl alcohol and water. This method is studied by measuring amplitude and phase of photodeflection signal in various frequency modulations. The experimental setup consists of two laser lines: 1) a pump laser beams through a modulator, varied frequency, controlled by lock-in amplifier and focused on sample surface by lens. 2) a probe laser which parallels with the sample surface and is perpendicular to the pump laser beam. The probe laser deflection signal is obtained by a position sensor which controlled by lock-in amplifier. Thermal diffusivity is calculated by measuring the amplitude and phase of the photodeflection signal and compared with the thermal diffusivity of a standard value. The thermal diffusivity of SGG agrees well with the literature but the thermal diffusivity of Cu is less than the literature value by a factor of ten. The experiment requires further improvement to measure the thermal diffusivity of Cu. However, we succeed in using ethyl alcohol as the coupling medium instead of CCl4 which is highly toxic.

Estimating Potential Effects of Hypothetical Oil Spills on Polar Bears

USGS Publications Warehouse

Amstrup, Steven C.; Durner, George M.; McDonald, T.L.; Johnson, W.R.

2006-01-01

Much is known about the transport and fate of oil spilled into the sea and its toxicity to exposed wildlife. Previously, however, there has been no way to quantify the probability that wildlife dispersed over the seascape would be exposed to spilled oil. Polar bears, the apical predator of the arctic, are widely dispersed near the continental shelves of the Arctic Ocean, an area also undergoing considerable hydrocarbon exploration and development. We used 15,308 satellite locations from 194 radiocollared polar bears to estimate the probability that polar bears could be exposed to hypothetical oil spills. We used a true 2 dimensional Gausian kernel density estimator, to estimate the number of bears likely to occur in each 1.00 km2 cell of a grid superimposed over near shore areas surrounding 2 oil production facilities: the existing Northstar oil production facility, and the proposed offshore site for the Liberty production facility. We estimated the standard errors of bear numbers per cell with bootstrapping. Simulated oil spill footprints for September and October, the times during which we hypothesized effects of an oil-spill would be worst, were estimated using real wind and current data collected between 1980 and 1996. We used ARC/Info software to calculate overlap (numbers of bears oiled) between simulated oil-spill footprints and polar bear grid-cell values. Numbers of bears potentially oiled by a hypothetical 5912 barrel spill (the largest spill thought probable from a pipeline breach) ranged from 0 to 27 polar bears for September open water conditions, and from 0 to 74 polar bears in October mixed ice conditions. Median numbers oiled by the 5912 barrel hypothetical spill from the Liberty simulation in September and October were 1 and 3 bears, equivalent values for the Northstar simulation were 3 and 11 bears. In October, 75% of trajectories from the 5912 barrel simulated spill at Liberty oiled 9 or fewer bears while 75% of the trajectories affected 20 or fewer polar bears when we simulated an October spill at the Northstar site. Northstar Island is nearer the active ice flaw zone than Liberty. Simulations suggested that oil spilled at Northstar would spread more effectively and more consistently into surrounding areas. Also, polar bear densities are consistently higher near Northstar. Oil spills simulated for the Liberty site were more erratic in the areas they covered and the numbers of bears impacted, and numbers of bears hypothetically exposed were usually smaller. Methods described here are broadly applicable to other dispersed marine wildlife. Key words: Arctic, Beaufort Sea, clustering, kernel, management, oil spill, polar bears, population delineation, radiotelemetry, satellite, smoothing, Ursus maritimus

Separation of toxic rhodamine B from aqueous solution using an efficient low-cost material, Azolla pinnata, by adsorption method.

PubMed

Kooh, Muhammad Raziq Rahimi; Lim, Linda B L; Lim, Lee Hoon; Dahri, Muhammad Khairud

2016-02-01

This study investigated the potential of untreated Azolla pinnata (AP) to remove toxic rhodamine B (RB) dye. The effects of adsorbent dosage, pH, ionic strength, contact time, and concentration were studied. Experiments involving the effects of pH and ionic strength indicated that hydrophobic-hydrophobic interactions might be the dominant force of attraction for the RB-AP adsorption system. The kinetics modelling of the kinetics experiment showed that pseudo-second-order best represented the adsorption process. The Weber-Morris intraparticle diffusion model showed that intraparticle diffusion is not the rate-limiting step, while the Boyd model suggested that film diffusion might be rate-limiting. The adsorption isotherm model, Langmuir, best represented the adsorption process, and the maximum adsorption capacity was predicted to be 72.2 and 199.7 mg g(-1) at 25 and 65 °C, respectively. Thermodynamics study indicates spontaneity, endothermic and physisorption-dominant adsorption process. The adsorbents were regenerated to satisfactory level with distilled water, HNO3 and NaOH. Pre-treatment of adsorbent with oxalic acid, citric acid, NaOH, HCl and phosphoric acid was investigated but the adsorption capacity was less than the untreated AP.

A novel microbial fuel cell sensor with a gas diffusion biocathode sensing element for water and air quality monitoring.

PubMed

Jiang, Yong; Liang, Peng; Huang, Xia; Ren, Zhiyong Jason

2018-07-01

Toxicity monitoring is essential for the protection of public health and ecological safety. Microbial fuel cell (MFC) sensors demonstrated good potential in toxicity monitoring, but current MFC sensors can only be used for anaerobic water monitoring. In this study, a novel gas diffusion (GD)-biocathode sensing element was fabricated using a simple method. The GD-biocathode MFC sensor can directly be used for formaldehyde detection (from 0.0005% to 0.005%) in both aerobic and anaerobic water bodies. Electrochemical analysis indicated that the response by the sensor was caused by the toxic inhibition to the microbial activity for the oxygen reduction reaction (ORR). This study for the first time demonstrated that the GD-biocathode MFC sensor has a detection limit of 20 ppm for formaldehyde and can be used to monitor air pollution. Selective sensitivity to formaldehyde was not achieved as the result of using a mixed-culture, which confirms that it can serve as a generic biosensor for monitoring gaseous pollutants. This study expands the realm of knowledge for MFC sensor applications. Copyright © 2018 Elsevier Ltd. All rights reserved.

Monitoring of Nonsteroidal Immunosuppressive Drugs in Patients With Lung Disease and Lung Transplant Recipients

PubMed Central

Meyer, Keith C; Nathanson, Ian; Angel, Luis; Bhorade, Sangeeta M; Chan, Kevin M; Culver, Daniel; Harrod, Christopher G; Hayney, Mary S; Highland, Kristen B; Limper, Andrew H; Patrick, Herbert; Strange, Charlie; Whelan, Timothy

2012-01-01

Objectives: Immunosuppressive pharmacologic agents prescribed to patients with diffuse interstitial and inflammatory lung disease and lung transplant recipients are associated with potential risks for adverse reactions. Strategies for minimizing such risks include administering these drugs according to established, safe protocols; monitoring to detect manifestations of toxicity; and patient education. Hence, an evidence-based guideline for physicians can improve safety and optimize the likelihood of a successful outcome. To maximize the likelihood that these agents will be used safely, the American College of Chest Physicians established a committee to examine the clinical evidence for the administration and monitoring of immunosuppressive drugs (with the exception of corticosteroids) to identify associated toxicities associated with each drug and appropriate protocols for monitoring these agents. Methods: Committee members developed and refined a series of questions about toxicities of immunosuppressives and current approaches to administration and monitoring. A systematic review was carried out by the American College of Chest Physicians. Committee members were supplied with this information and created this evidence-based guideline. Conclusions: It is hoped that these guidelines will improve patient safety when immunosuppressive drugs are given to lung transplant recipients and to patients with diffuse interstitial lung disease. PMID:23131960

Role of (18)F-FDG PET-CT in Monitoring the Cyclophosphamide Induced Pulmonary Toxicity in Patients with Breast Cancer - 2 Case Reports.

PubMed

Taywade, Sameer Kamalakar; Kumar, Rakesh; Bhethanabhotla, Sainath; Bal, Chandrasekhar

2016-09-01

Drug induced pulmonary toxicity is not uncommon with the use of various chemotherapeutic agents. Cyclophosphamide is a widely used chemotherapeutic drug in the treatment of breast cancer. Although rare, lung toxicity has been reported with cyclophosphamide use. Detection of bleomycin induced pulmonary toxicity and pattern of (18)F-fluorodeoxyglucose ((18)F-FDG) uptake in lungs on fluorodeoxyglucose positron emission tomography-computed tomography ((18)F-FDG PET-CT) has been elicited in literature in relation to lymphoma. However, limited data is available regarding the role of (18)F-FDG PET-CT in monitoring drug induced pulmonary toxicity in breast cancer. We here present two cases of cyclophosphamide induced drug toxicity. Interim (18)F-FDG PET-CT demonstrated diffusely increased tracer uptake in bilateral lung fields in both these patients. Subsequently there was resolution of lung uptake on (18)F-FDG PET-CT scan post completion of chemotherapy. These patients did not develop significant respiratory symptoms during chemotherapy treatment and in follow up.

Gallium-bearing sphalerite in a metal-sulfide nodule of the Qingzhen (EH3) chondrite

NASA Technical Reports Server (NTRS)

Rambaldi, E. R.; Rajan, R. S.; Housley, R. M.; Wang, D.

1986-01-01

The composition and possible history of the Qingshen (EH3) chondrite is presented. The chondrite contains a population of spheroidal metal-sulfide nodules, which display textural evidence of reheating and melting. Evidence of metal sulfuration is also present, suggesting replacement of metal by sulfide during melting. This process has led to the nucleation of perryite along metal-sulfide interfaces. The Ga-bearing sphalerite that was found may have formed by injection of molten sulfide droplets into the metal followed by subsolidus diffusion of Ga from the metal into the sulfide. The latter may occur because of Ga supersaturation in the metal during progressive sulfuration and its decreased affinity for the metal phase during cooling below the taenite-kamacite transition point.

Assessment of the geoavailability of trace elements from minerals in mine wastes: analytical techniques and assessment of selected copper minerals

USGS Publications Warehouse

Driscoll, Rhonda; Hageman, Phillip L.; Benzel, William M.; Diehl, Sharon F.; Adams, David T.; Morman, Suzette; Choate, LaDonna M.

2012-01-01

In this study, four randomly selected copper-bearing minerals were examined—azurite, malachite, bornite, and chalcopyrite. The objectives were to examine and enumerate the crystalline and chemical properties of each of the minerals, to determine which, if any, of the Cu-bearing minerals might adversely affect systems biota, and to provide a multi-procedure reference. Laboratory work included use of computational software for quantifying crystalline and amorphous material and optical and electron imaging instruments to model and project crystalline structures. Chemical weathering, human fluid, and enzyme simulation studies were also conducted. The analyses were conducted systematically: X-ray diffraction and microanalytical studies followed by a series of chemical, bio-leaching, and toxicity experiments.

Synthesis, analgesic activity, and binding properties of some epibatidine analogs with a tropine skeleton.

PubMed

Rádl, S; Hafner, W; Budesínsky, M; Hejnová, L; Krejcí, I

2000-06-01

A series of epibatidine analogs and their positional isomers bearing an 8-azabicyclo[3.2.1]octane moiety is described. Also some of their simplified analogs bearing a 3-piperidine moiety are reported. Their receptor binding profiles (5-HT1A, 5-HT1B, M1, M2, neuronal nicotinic receptor) and analgesic activity (hot plate, acetic acid induced writhing) have been studied. Some of the compounds, especially those containing an 8-azabicyclo[3.2.1]oct-2-ene moiety possess high afinity for the nicotinic cholinergic receptor. The most analgesically active compounds are also highly toxic. Optimized structures (PM3-MOPAC, Alchemy 2000, Tripos Inc.) of compounds 1-9 were compared with that of epibatidine.

Electric discharge for treatment of trace contaminants

NASA Technical Reports Server (NTRS)

Flamm, D. L.; Wydeven, T. J. (Inventor)

1978-01-01

A radio frequency glow discharge reactor is described for removing trace oxidizable contaminants from an oxygen bearing atmosphere. The reaction chamber is defined by an inner metal electrode facing a dielectric backed by an outer conductive electrode. In one embodiment, a conductive liquid forms the conductor of an outer electrode and cools the dielectric. A resonator coupled to a variable radio frequency source generates the high voltages for creating a glow discharge in the chamber at a predetermined pressure whereby the trace contaminants are oxidized into a few simple non-toxic products that may be easily recovered. The corresponding process for removal of trace contaminants from an oxygen-bearing atmosphere with high efficiency independent of the concentration level is also disclosed.

Comparative study between simple and optimized liposomal dispersion of quetiapine fumarate for diffusion through nasal route.

PubMed

Upadhyay, Pratik; Trivedi, Jatin; Pundarikakshudu, Kilambi; Sheth, Navin

2016-05-01

Nasal route of drug administration is preferred more and more for the targeted delivery to the brain in current drug development scenario due to its ease of use, reliability, quick action, and lesser side effects. Those CNS drugs which have limited oral bioavailability due to pharmacokinetic consequences and brain barrier repulsion are getting onto this direction. Quetiapine fumarate, an analogous to above and an antischizophrenic agent, is tested for its diffusion property with and without lipophilic carrier through sheep nasal membrane. Being a BCS class II' and high permeable candidate, it tends to crossover easily, so made up in a simple dispersion. To improve its diffusion rate, it was embedded into liposomal dispersion, which has proven that it has advanced efficiency for diffusion. For this, both the formulations were checked and compared for their diffusion profile, as it is an essential property for bioavailability through nasal route. Comparison was made on the basis of % drug diffusion within 6 h, rate, mechanism, profile, and coefficient. Liposomal dispersion has been proved superior with greater percentage diffusion of 32.61 ± 1.70 and very high permeability with a coefficient value of 4.1334 ± 0.7321 (× 10 (-) (5 )cm/s). Diffusion profile comparison bearing dissimilarity of 18 and similarity of 74 indicated that the diffusion profiles of liposomal dispersions and simple dispersion were similar but not identical. Liposomal diffusion supremacy was further sustained by in vivo, ciliotoxicity, and gamma scintigraphy studies.

Localization of damage in progressive hydroxychloroquine retinopathy on and off the drug: inner versus outer retina, parafovea versus peripheral fovea.

PubMed

de Sisternes, Luis; Hu, Julia; Rubin, Daniel L; Marmor, Michael F

2015-05-01

To evaluate the relative involvement of inner and outer retina in hydroxychloroquine (HCQ) retinopathy while on the drug, and after drug cessation, using data from spectral-domain optical coherence tomography (SD-OCT). A total of 102 SD-OCT scans were obtained from 11 patients (classified as having early, moderate, or severe stages of toxicity) over a period of 4 years after cessation of HCQ. The inner and outer retina boundaries were identified automatically to measure thickness and characterize progression topographically. The segmentation of retinal layers was verified in SD-OCT cross-sections for all eyes and scans included in this study (a total of 102 scans). Topographic analysis showed that inner retina was not involved in HCQ toxicity to any meaningful degree, either between stages of retinopathy or after the drug is stopped. The characteristic bull's eye pattern of outer macula thinning appears when comparing moderate retinopathy (before any RPE damage) to the early stage. Later damage, as toxicity evolved to a severe stage, was diffuse across most of the macula. If the drug was stopped at an early or moderate stage, progression was limited to the first year and occurred diffusely without parafoveal localization. Hydroxychloroquine retinopathy primarily involves outer retina (photoreceptors). Outer retinal thinning while using HCQ initially involves the parafovea, but becomes diffuse across the macula as damage progresses or after drug cessation. When HCQ is stopped at an early or moderate stage (before RPE damage), progression seems to be limited to the first year.

THE EFFECT OF KILLED BACTERIA ON THE SERUM FERMENTS AND ANTIFERMENT : STUDIES ON FERMENT ACTION. XXVII.

PubMed

Jobling, J W; Petersen, W; Eggstein, A A

1915-11-01

1. The intravenous injection of killed organisms is followed by the mobilization of a non-specific protease and lipase; the rapidity and extent of this reaction depend upon the toxicity of the organism and on the resistance of the organism to proteolysis. 2. The temperature and leucocytic curve bear no relation to the ferment changes. 3. The serum antiferment is usually increased after the injection. 4. Of the organisms studied, the typhoid bacilli produced the most marked ferment changes, and the tubercle bacilli the least. 5. The toxicity of the dried organisms cannot depend wholly upon proteolysis in vivo, but must depend in part on the preformed toxic substances liberated on lysis. 6. Serum protease should not be considered as the sole exciter of intoxication through the production of protein split products; it seems possible that its function may in part be one of detoxication.

Fulminant streptococcal toxic shock syndrome.

PubMed

Zavala, S; Arias, M; Legua, P

2018-03-01

We present a case of a previously healthy 37-year-old male who developed fever, nausea, vomiting, diarrhoea, and hypovolaemia. Within 5.5 h he presented with tachycardia, tachypnoea, became hypotensive and displayed a diffuse erythematous rash. In the following hours he developed persistent hypotension, acute respiratory distress syndrome, liver failure, kidney failure and disseminated intravascular coagulation. A diagnosis of toxic shock syndrome was made, but despite antibiotic therapy, immunoglobulin administration, and supportive measures, the patient died 50 h after presentation. Streptococcus pyogenes was isolated from blood cultures.

Early pregnancy exposure to feto-toxic medications among out-patients in Malawi.

PubMed

Kabuluzi, Ezereth; Campbell, Malcolm; McGowan, Linda; Chirwa, Ellen; Brabin, Loretta

2014-08-01

To estimate the proportion of women in early pregnancy prescribed potentially feto-toxic medications at an out-patient clinic in Malawi. Over six-months the number of women of child-bearing age attending out-patient clinics and prescribed medicines at Mitundu Community Hospital was derived from the hospital's registry and pharmacy records. Women prescribed potentially feto-toxic medicines (using Food and Drug Administration classifications) by medical assessments were subsequently interviewed and pregnancy tested. Exposure to potentially feto-toxic medications was estimated and differences between pregnant and non-pregnant women were described. Of 8970 female outpatients, 1012 (11.3%; 95% CI: 10.6% to 12%) were prescribed potentially feto-toxic medicines. After excluding 740 as unlikely to be pregnant, 209 women had negative pregnancy tests and 63 were confirmed as pregnant, representing one in 16 of women prescribed contraindicated medicines or between 2.8% and 3.5% of all women attending in early pregnancy. Most medicines were FDA rated C or D. Only 152 (55.9%) of these women had been asked about pregnancy and prescribing practices did not discriminate between pregnant and non-pregnant patients. Assessment and prescribing practices for women attending out-patient clinics who might be in early pregnancy were inadequate, increasing the risk of exposure to potentially feto-toxic medicines.

Strange kinetics of bulk-mediated diffusion on lipid bilayers

PubMed Central

Campagnola, Grace; Nepal, Kanti; Peersen, Olve B.

2016-01-01

Diffusion at solid-liquid interfaces is crucial in many technological and biophysical processes. Although its behavior seems deceivingly simple, recent studies showing passive superdiffusive transport suggest diffusion on surfaces may hide rich complexities. In particular, bulk-mediated diffusion occurs when molecules are transiently released from the surface to perform three-dimensional excursions into the liquid bulk. This phenomenon bears the dichotomy where a molecule always return to the surface but the mean jump length is infinite. Such behavior is associated with a breakdown of the central limit theorem and weak ergodicity breaking. Here, we use single-particle tracking to study the statistics of bulk-mediated diffusion on a supported lipid bilayer. We find that the time-averaged mean square displacement (MSD) of individual trajectories, the archetypal measure in diffusion processes, does not converge to the ensemble MSD but it remains a random variable, even in the long observation-time limit. The distribution of time averages is shown to agree with a Lévy flight model. Our results also unravel intriguing anomalies in the statistics of displacements. The time averaged MSD is shown to depend on experimental time and investigations of fractional moments show a scaling 〈|r(t)|q〉 ∼ tqv(q) with non-linear exponents, i.e. v(q) ≠ const. This type of behavior is termed strong anomalous diffusion and is rare among experimental observations. PMID:27095275

American option pricing in Gauss-Markov interest rate models

NASA Astrophysics Data System (ADS)

Galluccio, Stefano

1999-07-01

In the context of Gaussian non-homogeneous interest-rate models, we study the problem of American bond option pricing. In particular, we show how to efficiently compute the exercise boundary in these models in order to decompose the price as a sum of a European option and an American premium. Generalizations to coupon-bearing bonds and jump-diffusion processes for the interest rates are also discussed.

Occurrence modes of As, Sb, Te, Bi, Ag in sulfide assemblages of gold deposits of the Urals

NASA Astrophysics Data System (ADS)

Vikent'eva, O.; Vikentev, I.

2016-04-01

Review of occurrence modes of trace toxic elements ("potential pollutants") in ores from large gold deposits (the Urals) of different genetic types is presented. Mineral forms of these elements as well as their presence in main minerals from gold-bearing sulfide assemblages according to SEM, EPMA, INAA, ICP-MS and LA-ICP-MS are demonstrated.

Vascular infarction by subcutaneous application of tissue factor targeted to tumor vessels with NGR-peptides: activity and toxicity profile.

PubMed

Dreischalück, Johannes; Schwöppe, Christian; Spieker, Tilmann; Kessler, Torsten; Tiemann, Klaus; Liersch, Ruediger; Schliemann, Christoph; Kreuter, Michael; Kolkmeyer, Astrid; Hintelmann, Heike; Mesters, Rolf M; Berdel, Wolfgang E

2010-12-01

tTF-NGR consists of the extracellular domain of the (truncated) tissue factor (tTF), a central molecule for coagulation in vivo, and the peptide GNGRAHA (NGR), a ligand of the surface protein aminopeptidase N (CD13). After deamidation of the NGR-peptide moiety, the fusion protein is also a ligand for integrin αvβ3 (CD51/CD61). Both surface proteins are upregulated on endothelial cells of tumor vessels. tTF-NGR showed binding to specific binding sites on endothelial cells in vitro as shown by flow cytometry. Subcutaneous injection of tTF-NGR into athymic mice bearing human HT1080 fibrosarcoma tumors induced tumor growth retardation and delay. Contrast enhanced ultrasound detected a decrease in tumor blood flow in vivo after application of tTF-NGR. Histological analysis of the tumors revealed vascular disruption due to blood pooling and thrombotic occlusion of tumor vessels. Furthermore, a lack of resistance was shown by re-exposure of tumor-bearing mice to tTF-NGR after regrowth following a first cycle of treatment. However, after subcutaneous (s.c.) push injection with therapeutic doses (1-5 mg/kg bw) side effects have been observed, such as skin bleeding and reduced performance. Since lethality started within the therapeutic dose range (LD10 approximately 2 mg/kg bw) no safe therapeutic window could be found. Limiting toxicity was represented by thrombo-embolic events in major organ systems as demonstrated by histology. Thus, subcutaneous injection of tTF-NGR represents an active, but toxic application procedure and compares unfavourably to intravenous infusion.

Antitumor effect and toxicity of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles in mice bearing breast cancer

PubMed Central

2013-01-01

Background Magnetic fluids containing superparamagnetic iron oxide nanoparticles represent an attractive platform as nanocarriers in chemotherapy. Recently, we developed a formulation of maghemite nanoparticles coated with rhodium (II) citrate, which resulted in in vitro cytotoxicity enhanced up to 4.6 times when compared to free rhodium (II) citrate formulation on breast carcinoma cells. In this work, we evaluate the antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Methods Mice were evaluated with regard to the treatments’ toxicity through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine; DNA fragmentation and cell cycle of bone marrow cells; and liver, kidney and lung histology. In addition, the antitumor activity of rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate was verified by tumor volume reduction, histology and immunohistochemistry. Results Regarding the treatments’ toxicity, no experimental groups had alterations in levels of serum ALT or creatinine, and this suggestion was corroborated by the histopathologic examination of liver and kidney of mice. Moreover, DNA fragmentation frequency of bone marrow cells was lower than 15% in all experimental groups. On the other hand, the complexes rhodium (II) citrate-functionalized maghemite and free rhodium (II) citrate led to a marked growth inhibition of tumor and decrease in CD31 and Ki-67 staining. Conclusions In summary, we demonstrated that both rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate formulations exhibited antitumor effects against 4T1 metastatic breast cancer cell line following intratumoral administration. This antitumor effect was followed by inhibition of both cell proliferation and microvascularization and by tumor tissue injury characterized as necrosis and fibrosis. Remarkably, this is the first published report demonstrating the therapeutic efficacy of maghemite nanoparticles coated with rhodium (II) citrate. This treatment prolonged the survival period of treated mice without inducing apparent systemic toxicity, which strengthens its use for future breast cancer therapeutic applications. PMID:23414068

In vivo assessment of toxicity and pharmacokinetics of methylglyoxal

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

Ghosh, Manju; Talukdar, Dipa; Ghosh, Swapna

2006-04-01

Previous in vivo studies from several laboratories had shown remarkable curative effect of methylglyoxal on cancer-bearing animals. In contrast, most of the recent in vitro studies have assigned a toxic role for methylglyoxal. The present study was initiated with the objective to resolve whether methylglyoxal is truly toxic in vivo and to reassess its therapeutic potential. Four species of animals, both rodent and non-rodent, were treated with different doses of methylglyoxal through oral, subcutaneous and intravenous routes. Acute (treatment for only 1 day) toxicity tests had been done with mouse and rat. These animals received 2, 1 and 0.3 gmore » of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. Chronic (treatment for around a month) toxicity test had been done with mouse, rat, rabbit and dog. Mouse, rat and dog received 1, 0.3 and 0.1 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. Rabbit received 0.55, 0.3 and 0.1 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. It had been observed that methylglyoxal had no deleterious effect on the physical and behavioral pattern of the treated animals. Fertility and teratogenecity studies were done with rats that were subjected to chronic toxicity tests. It had been observed that these animals produced healthy litters indicating no damage of the reproductive systems as well as no deleterious effect on the offspring. Studies on several biochemical and hematological parameters of methylglyoxal-treated rats and dogs and histological studies of several organs of methylglyoxal-treated mouse were performed. These studies indicated that methylglyoxal had no apparent deleterious effect on some vital organs of these animals. A detailed pharmacokinetic study was done with mouse after oral administration of methylglyoxal. The effect of methylglyoxal alone and in combination with creatine and ascorbic acid on cancer-bearing animals had been investigated by measuring the increase in life span and tumor cell growth inhibition. The results indicated that anticancer effect of methylglyoxal was significantly augmented by ascorbic acid and further augmented by ascorbic acid and creatine. Nearly 80% of the animals treated with methylglyoxal plus ascorbic acid plus creatine were completely cured and devoid of any malignant cells within the peritoneal cavity.« less

Dynamics of Phenanthrenequinone on Carbon Nano-Onion Surfaces Probed by Quasielastic Neutron Scattering

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

Anjos, Daniela M; Mamontov, Eugene; Brown, Gilbert M

We used quasielastic neutron scattering (QENS) to study the dynamics of phenanthrenequinone (PQ) on the surface of onion-like carbon (OLC), or so called carbon onions, as a function of surface coverage and temperature. For both the high- and low-coverage samples, we observed two diffusion processes; a faster process and nearly an order of magnitude slower process. On the high-coverage surface, the slow diffusion process is of long-range translational character, whereas the fast diffusion process is spatially localized on the length scale of ~ 4.7 . On the low-coverage surface, both diffusion processes are spatially localized; on the same length scalemore » of ~ 4.7 for the fast diffusion and a somewhat larger length scale for the slow diffusion. Arrhenius temperature dependence is observed except for the long-range diffusion on the high-coverage surface. We attribute the fast diffusion process to the generic localized in-cage dynamics of PQ molecules, and the slow diffusion process to the long-range translational dynamics of PQ molecules, which, depending on the coverage, may be either spatially restricted, or long-range. On the low-coverage surface, uniform surface coverage is not attained, and the PQ molecules experience the effect of spatial constraints on their long-range translational dynamics. Unexpectedly, the dynamics of PQ molecules on OLC as a function of temperature and surface coverage bears qualitative resemblance to the dynamics of water molecules on oxide surfaces, including practically temperature-independent residence times for the low-coverage surface. The dynamics features that we observed may be universal across different classes of surface adsorbates.« less

Contribution of HI-bearing ultra-diffuse galaxies to the cosmic number density of galaxies

NASA Astrophysics Data System (ADS)

Jones, M. G.; Papastergis, E.; Pandya, V.; Leisman, L.; Romanowsky, A. J.; Yung, L. Y. A.; Somerville, R. S.; Adams, E. A. K.

2018-06-01

We estimate the cosmic number density of the recently identified class of HI-bearing ultra-diffuse sources (HUDs) based on the completeness limits of the ALFALFA survey. These objects have HI masses approximately in the range 8.5 < logMHI/M⊙ < 9.5, average r-band surface brightnesses fainter than 24 mag arcsec-2, half-light radii greater than 1.5 kpc, and are separated from neighbours by at least 350 kpc. In this work we demonstrate that they contribute at most 6% of the population of HI-bearing dwarfs detected by ALFALFA (with similar HI masses), have a total cosmic number density of (1.5 ± 0.6) × 10-3 Mpc-3, and an HI mass density of (6.0 ± 0.8) × 105 M⊙ Mpc-3. We estimate that this is similar to the total cosmic number density of ultra-diffuse galaxies (UDGs) in groups and clusters, and conclude that the relation between the number of UDGs hosted in a halo and the halo mass must have a break below M200 1012 M⊙ in order to account for the abundance of HUDs in the field. The distribution of the velocity widths of HUDs rises steeply towards low values, indicating a preference for slow rotation rates compared to the global HI-rich dwarf population. These objects were already included in previous measurements of the HI mass function, but have been absent from measurements of the galaxy stellar mass function owing to their low surface brightness. However, we estimate that due to their low number density the inclusion of HUDs would constitute a correction of less than 1%. Comparison with the Santa Cruz semi-analytic model shows that it produces HI-rich central UDGs that have similar colours to HUDs, but that these UDGs are currently produced in a much greater number. While previous results from this sample have favoured formation scenarios where HUDs form in high spin-parameter halos, comparisons with recent results which invoke that formation mechanism reveal that this model produces an order of magnitude more field UDGs than we observe in the HUD population, and these have an occurrence rate (relative to other dwarfs) that is approximately double what we observe. In addition, the colours of HUDs are bluer than predicted, although we suspect this is due to a systematic problem in reproducing the star formation histories of low-mass galaxies rather than being specific to the ultra-diffuse nature of these sources.

Dosimetric and Clinical Outcomes With Intensity Modulated Radiation Therapy After Chemotherapy for Patients With Early-Stage Diffuse Large B-cell Lymphoma of Waldeyer Ring

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

Xu, Yong-Gang; Qi, Shu-Nan; Wang, Shu-Lian

Purpose: To assess the dosimetric benefit, prognosis, and toxicity of intensity modulated radiation therapy (IMRT) for early-stage, diffuse large B-cell lymphoma of Waldeyer ring (WR-DLBCL). Methods and Materials: Sixty-one patients with early-stage WR-DLBCL who received chemotherapy followed by IMRT were retrospectively reviewed. Dosimetric parameters for the target volume and critical normal structures were evaluated, and survival was calculated. Linear regression analysis was used to assess the effect of the mean dose (D{sub mean}) to the parotid glands on xerostomia. Results: The median conformity index and homogeneity index of the planning target volume (PTV) were 0.83 and 0.90, respectively, demonstrating verymore » good coverage of the target volume. The mean dose to the parotid glands was 24.9 Gy. The 5-year overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) were 94.7%, 93.1%, and 98.3%, respectively. Early and late toxicities were mild, and no patient experienced late grade ≥3 toxicities. The D{sub mean} to the parotid glands had a linear correlation with late grade ≥2 xerostomia. Conclusions: IMRT after chemotherapy can provide excellent dose conformity and achieve favorable survival and LRC with mild toxicities in patients with early-stage WR-DLBCL. Dose constraints for the parotid glands should be limited to <24 Gy for early-stage WR-DLBCL.« less

Model for the interpretation of nuclear magnetic resonance relaxometry of hydrated porous silicate materials

NASA Astrophysics Data System (ADS)

Faux, D. A.; Cachia, S.-H. P.; McDonald, P. J.; Bhatt, J. S.; Howlett, N. C.; Churakov, S. V.

2015-03-01

Nuclear magnetic resonance (NMR) relaxation experimentation is an effective technique for probing the dynamics of proton spins in porous media, but interpretation requires the application of appropriate spin-diffusion models. Molecular dynamics (MD) simulations of porous silicate-based systems containing a quasi-two-dimensional water-filled pore are presented. The MD simulations suggest that the residency time of the water on the pore surface is in the range 0.03-12 ns, typically 2-5 orders of magnitude less than values determined from fits to experimental NMR measurements using the established surface-layer (SL) diffusion models of Korb and co-workers [Phys. Rev. E 56, 1934 (1997), 10.1103/PhysRevE.56.1934]. Instead, MD identifies four distinct water layers in a tobermorite-based pore containing surface Ca2 + ions. Three highly structured water layers exist within 1 nm of the surface and the central region of the pore contains a homogeneous region of bulklike water. These regions are referred to as layer 1 and 2 (L1, L2), transition layer (TL), and bulk (B), respectively. Guided by the MD simulations, a two-layer (2L) spin-diffusion NMR relaxation model is proposed comprising two two-dimensional layers of slow- and fast-moving water associated with L2 and layers TL+B, respectively. The 2L model provides an improved fit to NMR relaxation times obtained from cementitious material compared to the SL model, yields diffusion correlation times in the range 18-75 ns and 28-40 ps in good agreement with MD, and resolves the surface residency time discrepancy. The 2L model, coupled with NMR relaxation experimentation, provides a simple yet powerful method of characterizing the dynamical properties of proton-bearing porous silicate-based systems such as porous glasses, cementitious materials, and oil-bearing rocks.

Removal and toxicity reduction of naphthenic acids by ozonation and combined ozonation-aerobic biodegradation.

PubMed

Vaiopoulou, Eleni; Misiti, Teresa M; Pavlostathis, Spyros G

2015-03-01

A commercial naphthenic acids (NAs) mixture (TCI Chemicals) and five model NA compounds were ozonated in a semibatch mode. Ozonation of 25 and 35 mg/L NA mixture followed pseudo first-order kinetics (k(obs)=0.11±0.008 min(-1); r(2)=0.989) with a residual NAs concentration of about 5 mg/L. Ozone reacted preferentially with NAs of higher cyclicity and molecular weight and decreased both cyclicity and the acute Microtox® toxicity by 3.3-fold. The ozone reactivity with acyclic and monocyclic model NAs varied and depended on other structural features, such as branching and the presence of tertiary or quaternary carbons. Batch aerobic degradation of unozonated NA mixture using a NA-enriched culture resulted in 83% NA removal and a 6.7-fold decrease in toxicity, whereas a combination of ozonation-biodegradation resulted in 89% NA removal and a 15-fold decrease in toxicity. Thus, ozonation of NA-bearing waste streams coupled with biodegradation are effective treatment processes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Preclinical evaluation of zinc phthalocyanine tetrasulfonate-based PDT

NASA Astrophysics Data System (ADS)

Borgatti-Jeffreys, Antonella; Hooser, Stephen B.; Miller, Margaret A.; Thomas, Rose M.; deGortari, Amalia; Lucroy, Michael D.

2005-04-01

Photodynamic therapy (PDT) involves the light activation of a drug within a tumor causing selective tumor cell death. Unfortunately, some photosensitizing drugs have been associated with adverse reactions in veterinary patients. Zinc phthalocyanine tetrasulfonate (ZnPcS4) is a promising second-generation photosensitizer for use in veterinary medicine, however, it cannot be applied clinically until safety and efficacy data are available. ZnPcS4 was given to Swiss Webster mice to assess acute toxicity. Doses >100 mg/kg were associated with acute toxicity and mortality, and doses >100 mg/kg resulted in renal tubular nephrosis, suggesting that the minimum toxic dose is approximately 100 mg/kg. Based on these data, a Phase I clinical trial of ZnPcS4-based PDT in tumor-bearing dogs is underway, with ZnPcS4 doses up to 2 mg/kg producing no apparent toxicity. Tumor response has been observed after ZnPcS4-based PDT using doses as low as 0.25 mg/kg, suggesting that conventional phase I clinical trials may not be appropriate for PDT protocols.

Enhancement by O6-benzyl-N2-acetylguanosine of N'-[2-chloroethyl]-N-[2-(methylsulphonyl)ethyl]-N'-nitrosourea therapeutic index on nude mice bearing resistant human melanoma.

PubMed Central

Debiton, E.; Cussac-Buchdhal, C.; Mounetou, E.; Rapp, M.; Dupuy, J. M.; Maurizis, J. C.; Veyre, A.; Madelmont, J. C.

1997-01-01

The exposure of cells to O6-benzyl-N2-acetylguanosine (BNAG) and several guanine derivatives is known to reduce the activity of O6-alkylguanine-DNA alkyltransferase (MGMT) and to enhance the sensitivity of Mer+ (methyl enzyme repair positive) tumour cells to chloroethylnitrosoureas (CENUs) in vitro and in vivo. High water solubility and the pharmacokinetic properties of BNAG make it a candidate for simultaneous administration with CENUs by the i.v. route in human clinical use. In vivo we have shown previously that BNAG significantly increases the efficiency of N'-[2-chloroethyl]-N-[2-(methylsulphonyl)ethyl]-N'-nitrosourea (cystemustine) against M4Beu melanoma cells (Mer+) through its cytostatic activity by the i.p. route, but also increases its toxicity. To investigate the toxicity of BNAG and cystemustine when administered simultaneously in mice, we compared the maximum tolerated dose and LD50 doses of cystemustine alone or in combination with 40 mg kg(-1) BNAG by the i.p. route. The toxicity of cystemustine was enhanced by a factor of almost 1.44 when combined with BNAG. To compare the therapeutic index of cystemustine alone and the cystemustine/BNAG combination, pharmacological tests were carried out in nude mice bearing Mer+ M4Beu human melanoma cells. Isotoxic doses were calculated using the 1.44 ratio. The treatments were administered three times by the i.v. route on days 1, 5 and 9 after s.c. inoculation of tumour cells. Although the toxicities of the treatments were equal, BNAG strongly enhanced tumour growth inhibition. These results demonstrate the increase of the therapeutic index of cystemustine by BNAG and justify the use of BNAG to enhance nitrosourea efficiency in vivo by i.v. co-injection. PMID:9365163

Permeability and porosity of hydrate-bearing sediments in the northern Gulf of Mexico

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

Daigle, Hugh; Cook, Ann; Malinverno, Alberto

Hydrate-bearing sands are being actively explored because they contain the highest concentrations of hydrate and are the most economically recoverable hydrate resource. However, relatively little is known about the mechanisms or timescales of hydrate formation, which are related to methane supply, fluid flux, and host sediment properties such as permeability. We used logging-while-drilling data from locations in the northern Gulf of Mexico to develop an effective medium theory-based model for predicting permeability based on clay-sized sediment fraction. The model considers permeability varying between sand and clay endpoint permeabilities that are defined from laboratory data. We verified the model using permeabilitymore » measurements on core samples from three boreholes, and then used the model to predict permeability in two wells drilled in Walker Ridge Block 313 during the Gulf of Mexico Gas Hydrate Joint Industry Project Leg II expedition in 2009. We found that the cleanest sands (clay-sized fraction <0.05) had intrinsic (hydrate-free) permeability contrasts of 5-6 orders of magnitude with the surrounding clays, which is sufficient to provide focused hydrate formation due to advection of methane from a deep source or diffusion of microbial methane from nearby clay layers. In sands where the clay-sized fraction exceeds 0.05, the permeability reduces significantly and focused flow is less pronounced. In these cases, diffusion of dissolved microbial methane is most likely the preferred mode of methane supply for hydrate formation. In conclusion, our results provide important constraints on methane supply mechanisms in the Walker Ridge area and have global implications for evaluating rates of methane migration and hydrate formation in hydrate-bearing sands.« less

Permeability and porosity of hydrate-bearing sediments in the northern Gulf of Mexico

DOE PAGES

Daigle, Hugh; Cook, Ann; Malinverno, Alberto

2015-10-14

Hydrate-bearing sands are being actively explored because they contain the highest concentrations of hydrate and are the most economically recoverable hydrate resource. However, relatively little is known about the mechanisms or timescales of hydrate formation, which are related to methane supply, fluid flux, and host sediment properties such as permeability. We used logging-while-drilling data from locations in the northern Gulf of Mexico to develop an effective medium theory-based model for predicting permeability based on clay-sized sediment fraction. The model considers permeability varying between sand and clay endpoint permeabilities that are defined from laboratory data. We verified the model using permeabilitymore » measurements on core samples from three boreholes, and then used the model to predict permeability in two wells drilled in Walker Ridge Block 313 during the Gulf of Mexico Gas Hydrate Joint Industry Project Leg II expedition in 2009. We found that the cleanest sands (clay-sized fraction <0.05) had intrinsic (hydrate-free) permeability contrasts of 5-6 orders of magnitude with the surrounding clays, which is sufficient to provide focused hydrate formation due to advection of methane from a deep source or diffusion of microbial methane from nearby clay layers. In sands where the clay-sized fraction exceeds 0.05, the permeability reduces significantly and focused flow is less pronounced. In these cases, diffusion of dissolved microbial methane is most likely the preferred mode of methane supply for hydrate formation. In conclusion, our results provide important constraints on methane supply mechanisms in the Walker Ridge area and have global implications for evaluating rates of methane migration and hydrate formation in hydrate-bearing sands.« less

Vanadium(III)-l-cysteine enhances the sensitivity of murine breast adenocarcinoma cells to cyclophosphamide by promoting apoptosis and blocking angiogenesis.

PubMed

Basu, Abhishek; Bhattacharjee, Arin; Baral, Rathindranath; Biswas, Jaydip; Samanta, Amalesh; Bhattacharya, Sudin

2017-05-01

Various epidemiological and preclinical studies have already established the cancer chemopreventive potential of vanadium-based compounds. In addition to its preventive efficacy, studies have also indicated the abilities of vanadium-based compounds to induce cell death selectively toward malignant cells. Therefore, the objective of the present investigation is to improve the therapeutic efficacy and toxicity profile of an alkylating agent, cyclophosphamide, by the concurrent use of an organovanadium complex, vanadium(III)-l-cysteine. In this study, vanadium(III)-l-cysteine (1 mg/kg body weight, per os) was administered alone as well as in combination with cyclophosphamide (25 mg/kg body weight, intraperitoneal) in concomitant and pretreatment schedule in mice bearing breast adenocarcinoma cells. The results showed that the combination treatment significantly decreased the tumor burden and enhanced survivability of tumor-bearing mice through generation of reactive oxygen species in tumor cells. These ultimately led to DNA damage, depolarization of mitochondrial membrane potential, and apoptosis in tumor cells. Further insight into the molecular pathway disclosed that the combination treatment caused upregulation of p53 and Bax and suppression of Bcl-2 followed by the activation of caspase cascade and poly (ADP-ribose) polymerase cleavage. Administration of vanadium(III)-l-cysteine also resulted in significant attenuation of peritoneal vasculature and sprouting of the blood vessels by decreasing the levels of vascular endothelial growth factor A and matrix metalloproteinase 9 in the ascites fluid of tumor-bearing mice. Furthermore, vanadium(III)-l-cysteine significantly attenuated cyclophosphamide-induced hematopoietic, hepatic, and genetic damages and provided additional survival advantages. Hence, this study suggested that vanadium(III)-l-cysteine may offer potential therapeutic benefit in combination with cyclophosphamide by augmenting anticancer efficacy and diminishing toxicity to the host.

Improved antiangiogenic and antitumour activity of the combination of the natural flavonoid fisetin and cyclophosphamide in Lewis lung carcinoma-bearing mice

PubMed Central

Touil, Yasmine S.; Seguin, Johanne; Scherman, Daniel; Chabot, Guy G.

2011-01-01

Purpose The natural flavonoid fisetin was recently identified as a lead compound that stabilizes endothelial cell microtubules. In this study we investigated the antiproliferative and antiangiogenic properties of fisetin in vitro and in vivo. Methods Fisetin cytotoxicity was evaluated using Lewis lung carcinoma cells (LLC), endothelial cells and NIH 3T3 cells. Endothelial cell (EC) migration and capillary-like structure formation were evaluated using EAhy 926 cells. In vivo tumour growth inhibition studies were performed using LLC bearing mice treated with fisetin and/or cyclophosphamide (CPA). Results The fisetin IC50 was 59 μM for LLC and 77 μM for EC cells, compared to 210 μM for normal NIH 3T3 cells (24 h). Fisetin inhibited EC migration and capillary-like structure formation at non-cytotoxic concentrations (22–44 μM). In mice, fisetin inhibited angiogenesis assessed using the Matrigel plug assay. In LLC bearing mice, fisetin produced a 67% tumour growth inhibition (223 mg/kg, intraperitoneal), similar to the 66% produced by low dose CPA (30 mg/kg, subcutaneous). When fisetin and CPA were combined, however, a marked improvement in antitumour activity was observed (92% tumour growth inhibition), with low systemic toxicity. Tumour histology showed decreased microvessel density with either fisetin or CPA alone, and a dramatic decrease after the fisetin/CPA combination. Conclusions We have shown that fisetin not only displays in vitro and in vivo antiangiogenic properties, but that it can also markedly improve the in vivo antitumour effect of CPA. We propose that this drug combination associating a non-toxic dietary flavonoid with a cytotoxic agent could advantageously be used in the treatment of solid tumours. PMID:21069336

The isotope mass effect on chlorine diffusion in dacite melt, with implications for fractionation during bubble growth

NASA Astrophysics Data System (ADS)

Fortin, Marc-Antoine; Watson, E. Bruce; Stern, Richard

2017-12-01

Previous experimental studies have revealed that the difference in diffusivity of two isotopes can be significant in some media and can lead to an observable fractionation effect in silicate melts based on isotope mass. Here, we report the first characterization of the difference in diffusivities of stable isotopes of Cl (35Cl and 37Cl). Using a piston-cylinder apparatus, we generated quenched melts of dacitic composition enriched in Cl; from these we fabricated diffusion couples in which Cl atoms were induced to diffuse in a chemical gradient at 1200 to 1350 °C and 1 GPa. We analyzed the run products by secondary ion mass spectrometry (SIMS) for their isotopic compositions along the diffusion profiles, and we report a diffusivity ratio for 37Cl/35Cl of 0.995 ± 0.001 (β = 0.09 ± 0.02). No significant effect of temperature on the diffusivity ratio was discernable over the 150 °C range covered by our experiments. The observed 0.5% difference in diffusivity of the two isotopes could affect our interpretation of isotopic measurements of Cl isotopes in bubble-bearing or degassed magmas, because bubble growth is regulated in part by the diffusive supply of volatiles to the bubble from the surrounding melt. Through numerical simulations, we constrain the extent of Cl isotopic fractionation between bubble and host melt during this process. Bubble growth rates vary widely in nature-which implies a substantial range in the expected magnitude of isotopic fractionation-but plausible growth scenarios lead to Cl isotopic fractionations up to about 5‰ enrichment of 35Cl relative to 37Cl in the bubble. This effect should be considered when interpreting Cl isotopic measurements of systems that have experienced vapor exsolution.

POLLUTION PREVENTION TECHNOLOGY DIFFUSION INITIATIVE (TDI)

EPA Science Inventory

Although pollution prevention (P2) technologies save money and help prevent the release of toxic and hazardous wastes into the environment, many companies are reluctant to install new equipment or change the current processes. Some of the reluctance is initiated by lack of time a...

(Almost) Dark Galaxies in the ALFALFA Survey: HI-bearing Ultra-Diffuse Galaxies, and Beyond

NASA Astrophysics Data System (ADS)

Leisman, Luke; Haynes, Martha P.; Giovanelli, Riccardo; ALFALFA Almost Darks Team

2017-01-01

Scaling relations between HI and stars in galaxies suggest strong ties between their atomic gas content and star formation laws. The Arecibo Legacy Fast ALFA (ALFALFA) blind extragalactic HI survey is well positioned to locate very low surface brightness sources that lie off these relations, the most extreme of which may fall below optical detection limits. Thus, the ALFALFA (Almost) Darks Project has been investigating extreme outliers from these relations by studying the ~1% of ALFALFA sources without apparent stellar counterparts in major optical surveys. We have obtained deep HI and optical imaging of 25 of these candidate "dark" sources. We find that most "dark" sources are not extreme "(almost) dark" galaxies. A few are rare OH Megamasers, redshifted into the ALFALFA bandpass, and many are part of large galactic plumes, stretching as far as 600 kpc from their host galaxy. However, a small handful of sources appear to be galaxies with extreme stellar systems. We find multiple systems with HI mass to stellar mass ratios an order of magnitude larger than typical gas rich dwarfs. Further, we find an isolated population of HI-bearing "ultra diffuse" galaxies (UDGs), with stellar masses of dwarfs, but HI and optical radii of L* galaxies. We suggest that these sources may be related to recently reported gas poor, quiescent UDGs.

The diffusion of water in haploanesite

NASA Astrophysics Data System (ADS)

Ni, H.; Zhang, Y.

2008-12-01

Diffusive transport of water in silicate melts is a key process in magma dynamics and volcanic eruptions, including bubble growth. Previous studies demonstrate that in additional to temperature, water content and pressure, melt composition also plays an important role in determining water diffusivity. We carried out high temperature (1311-1512°C) diffusion-couple experiments and intermediate temperature (470- 600°C) dehydration experiments to investigate H2O diffusion in a melt of haploandesitic composition. The diffusion couple is composed of an anhydrous (with <0.1 wt.% H2O) and a hydrous (with 2 wt.% H2O) haploandesitic glass. A platinum capsule is used to contain the couple and then it is welded shut. Diffusion runs are carried out in a 12.7-mm piston-cylinder apparatus at 1 GPa and superliquidus temperatures of 1584-1785 K. Infrared microscopy is applied on quenched glass to measure the profile of total H2O concentration (H2Ot). The profile shape is best fit by an error function, indicating an H2O diffusivity virtually independent of H2O concentration, consistent with the results of Behrens et al. (2004) on an Fe-bearing andesite. Dehydration experiments are performed at 743-873 K in a rapid-quench cold-seal vessel, with a heated hydrous glass losing water to 0.1 GPa Ar atmosphere. Measured diffusion profiles, however, show that water diffusivity is dependent on water content. Experimental data can be explained by H2Om being the dominating diffusant or a total H2O diffusivity proportional to total H2O content. The distinction between the high-temperature experiments where H2Ot diffusivity is apparently independent of H2Ot content, and the intermediate-temperature experiments where H2Ot diffusivity depends on H2Ot can be rationalized if OH diffusion has a higher activation energy than molecular H2O diffusion, and their comparable diffusivities at high T gradually diverge as temperature is lowered. At below 1 wt.% H2O, water diffusivity increases from rhyolite to dacite to andesite at >1300°C, and this sequence is reversed at <600°C.

Clay and DOPA containing polyelectrolyte multilayer film for imparting anticorrosion properties to galvanized steel.

PubMed

Faure, Emilie; Halusiak, Emilie; Farina, Fabrice; Giamblanco, Nicoletta; Motte, Cécile; Poelman, Mireille; Archambeau, Catherine; Van de Weerdt, Cécile; Martial, Joseph; Jérôme, Christine; Duwez, Anne-Sophie; Detrembleur, Christophe

2012-02-07

A facile and green approach is developed to impart remarkable protection against corrosion to galvanized steel. A protecting multilayer film is formed by alternating the deposition of a polycation bearing catechol groups, used as corrosion inhibitors, with clay that induces barrier properties. This coating does not affect the esthetical aspect of the surface and does not release any toxic molecules in the environment.

Polychlorinated dibenzo-p-dioxins and dibenzofurans in the atmosphere around the Great Lakes.

PubMed

Venier, Marta; Ferrario, Joseph; Hites, Ronald A

2009-02-15

The atmospheric concentrations of PCDDs and PCDFs were measured in four sites near the shores of the North American Great Lakes. The sites included an urban site (Chicago, Illinois) and three rural/remote sites (Eagle Harbor, Michigan; Sleeping Bear Dunes, Michigan; and Sturgeon Point, New York). Sampling occurred every 24 days between November 2004 and December 2007. The concentration of PCDD/Fs averaged 2.3 +/- 0.2 fg WHO TEQ/m3 at Eagle Harbor, 35 +/- 3 fg WHO TEO/ m3 at Chicago, 7.4 +/- 1.4 fg WHO TEO/m3 at Sleeping Bear Dunes, and 13 +/- 2 fg WHO TED/m3 at Sturgeon Point. The total concentration of the 17 toxic PCDD/F congeners showed a significant seasonal trend at all sites, except Chicago. The date of maximum concentration averaged Dec 6 +/- 35 days, which is consistent with residential heating being an important source of PCDD/Fs to the atmosphere. A significant positive relationship between the logarithm of the total concentration of the 17 toxic PCDD/F congeners and the logarithm of the number of people within a 25 km radius around the sampling site was found. We suggest that urban and industrial areas, which are heavily populated, act as sources of PCDDs and PCDFs to the atmosphere.

Subsynchronous vibrations in a high pressure centrifugal compressor: A case history

NASA Technical Reports Server (NTRS)

Evans, B. F.; Smalley, A. J.

1984-01-01

Two distinct aerodynamically excited vibrations in a high pressure low flow centrifugal compressor are documented. A measured vibration near 21% of running speed was identified as a nonresonant forced vibration which results from rotating stall in the diffuser; a measured vibration near 50% of running speed was identified as a self excited vibration sustained by cross coupling forces acting at the compressor wheels. The dependence of these characteristics on speed, discharge pressure, and changes in bearing design are shown. The exciting mechanisms of diffuser stall and aerodynamic cross coupling are evidenced. It is shown how the rotor characteristics are expected to change as a result of modifications. The operation of the compressor after the modifications is described.

Treatment of boundary conditions in through-diffusion: A case study of (85)Sr(2+) diffusion in compacted illite.

PubMed

Glaus, M A; Aertsens, M; Maes, N; Van Laer, L; Van Loon, L R

2015-01-01

Valuable techniques to measure effective diffusion coefficients in porous media are an indispensable prerequisite for a proper understanding of the migration of chemical-toxic and radioactive micropollutants in the subsurface and geosphere. The present article discusses possible pitfalls and difficulties in the classical through-diffusion technique applied to situations where large diffusive fluxes of cations in compacted clay minerals or clay rocks occur. The results obtained from a benchmark study, in which the diffusion of (85)Sr(2+) tracer in compacted illite has been studied using different experimental techniques, are presented. It is shown that these techniques may yield valuable results provided that an appropriate model is used for numerical simulations. It is further shown that effective diffusion coefficients may be systematically underestimated when the concentration at the downstream boundary is not taken adequately into account in modelling, even for very low concentrations. A criterion is derived for quasi steady-state situations, by which it can be decided whether the simplifying assumption of a zero-concentration at the downstream boundary in through-diffusion is justified or not. The application of the criterion requires, however, knowledge of the effective diffusion coefficient of the clay sample. Such knowledge is often absent or only approximately available during the planning phase of a diffusion experiment. Copyright © 2015 Elsevier B.V. All rights reserved.

COMBINED AND INTERACTIVE EFFECTS OF GLOBAL CLIMATE CHANGE AND TOXICANTS ON POPULATIONS AND COMMUNITIES

PubMed Central

Moe, S Jannicke; De Schamphelaere, Karel; Clements, William H; Sorensen, Mary T; Van den Brink, Paul J; Liess, Matthias

2013-01-01

Increased temperature and other environmental effects of global climate change (GCC) have documented impacts on many species (e.g., polar bears, amphibians, coral reefs) as well as on ecosystem processes and species interactions (e.g., the timing of predator–prey interactions). A challenge for ecotoxicologists is to predict how joint effects of climatic stress and toxicants measured at the individual level (e.g., reduced survival and reproduction) will be manifested at the population level (e.g., population growth rate, extinction risk) and community level (e.g., species richness, food-web structure). The authors discuss how population- and community-level responses to toxicants under GCC are likely to be influenced by various ecological mechanisms. Stress due to GCC may reduce the potential for resistance to and recovery from toxicant exposure. Long-term toxicant exposure can result in acquired tolerance to this stressor at the population or community level, but an associated cost of tolerance may be the reduced potential for tolerance to subsequent climatic stress (or vice versa). Moreover, GCC can induce large-scale shifts in community composition, which may affect the vulnerability of communities to other stressors. Ecological modeling based on species traits (representing life-history traits, population vulnerability, sensitivity to toxicants, and sensitivity to climate change) can be a promising approach for predicting combined impacts of GCC and toxicants on populations and communities. Environ. Toxicol. Chem. 2013;32:49–61. © 2012 SETAC PMID:23147390

Acute Oral Toxicity of DIGL-RP Solid Propellant in Sprague-Dawley Rats

DTIC Science & Technology

1989-11-30

protein droplet and cast formation, glomeruli and cortical tubules Liver--diffuse vacuolation Stomach--multifocal, acute, necrotizing gastritis ...The choice of tissues examined histologically was biased by gross evaluation. Indications of renal protein loss were noted in five animals (casts and

Tacrolimus, Bortezomib, & Thymoglobulin in Preventing Low Toxicity GVHD in Donor Blood Stem Cell Transplant Patients

ClinicalTrials.gov

2018-03-30

Acute Leukemia; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Diffuse Large B-Cell Lymphoma; Follicular Lymphoma; Graft Versus Host Disease; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Myelodysplastic Syndrome; Myelofibrosis; Myeloproliferative Neoplasm; Small Lymphocytic Lymphoma

Impacts of aircraft deicer and anti-icer runoff on receiving waters from Dallas/Fort Worth International Airport, Texas, USA

USGS Publications Warehouse

Corsi, S.R.; Harwell, G.R.; Geis, S.W.; Bergman, D.

2006-01-01

From October 2002 to April 2004, data were collected from Dallas/Fort Worth (DFW) International Airport (TX, USA) outfalls and receiving waters (Trigg Lake and Big Bear Creek) to document the magnitude and potential effects of aircraft deicer and anti-icer fluid (ADAF) runoff on water quality. Glycol concentrations at outfalls ranged from less than 18 to 23,800 mg/L, whereas concentrations in Big Bear Creek were less because of dilution, dispersion, and degradation, ranging from less than 18 to 230 mg/L. Annual loading results indicate that 10 and 35% of what was applied to aircraft was discharged to Big Bear Creek in 2003 and 2004, respectively. Glycol that entered Trigg Lake was diluted and degraded before reaching the lake outlet. Dissolved oxygen (DO) concentrations at airport outfalls sometimes were low (5.0 mg/L). Results of toxicity tests indicate that effects on Ceriodaphnia dubia, Pimephales promelas, and Selanastrum capricornutum are influenced by type IV ADAF (anti-icer), not just type I ADAF (deicer) as is more commonly assumed. ?? 2006 SETAC.

Phloroglucinol Inhibits the Bioactivities of Endothelial Progenitor Cells and Suppresses Tumor Angiogenesis in LLC-Tumor-Bearing Mice

PubMed Central

Kwon, Yi-Hong; Jung, Seok-Yun; Kim, Jae-Won; Lee, Sang-Hun; Lee, Jun-Hee; Lee, Boo-Yong; Kwon, Sang-Mo

2012-01-01

Background There is increasing evidence that phloroglucinol, a compound from Ecklonia cava, induces the apoptosis of cancer cells, eventually suppressing tumor angiogenesis. Methodology/Principal Findings This is the first report on phloroglucinol's ability to potentially inhibit the functional bioactivities of endothelial progenitor cells (EPCs) and thereby attenuate tumor growth and angiogenesis in the Lewis lung carcinoma (LLC)-tumor-bearing mouse model. Although Phloroglucinol did not affect their cell toxicity, it specifically inhibited vascular endothelial growth factor (VEGF) dependent migration and capillary-like tube formation of EPCs. Our matrigel plug assay clearly indicated that orally injected phloroglucinol effectively disrupts VEGF-induced neovessel formation. Moreover, we demonstrated that when phloroglucinol is orally administered, it significantly inhibits tumor growth and angiogenesis as well as CD45−/CD34+ progenitor mobilization into peripheral blood in vivo in the LLC-tumor-bearing mouse model. Conclusions/Significance These results suggest a novel role for phloroglucinol: Phloroglucinol might be a modulator of circulating EPC bioactivities, eventually suppressing tumorigenesis. Therefore, phloroglucinol might be a candidate compound for biosafe drugs that target tumor angiogenesis. PMID:22496756

Sunitinib in relapsed or refractory diffuse large B-cell lymphoma: a clinical and pharmacodynamic phase II multicenter study of the NCIC Clinical Trials Group.

PubMed

Buckstein, Rena; Kuruvilla, John; Chua, Neil; Lee, Christina; Macdonald, David A; Al-Tourah, Abdulwahab J; Foo, Alison H; Walsh, Wendy; Ivy, S Percy; Crump, Michael; Eisenhauer, Elizabeth A

2011-05-01

There are limited effective therapies for most patients with relapsed diffuse large B-cell lymphoma (DLBCL). We conducted a phase II trial of the multi-targeted vascular endothelial growth factor receptor (VEGFR) kinase inhibitor, sunitinib, 37.5 mg given orally once daily in adult patients with relapsed or refractory DLBCL. Of 19 enrolled patients, 17 eligible patients were evaluable for toxicity and 15 for response. No objective responses were seen and nine patients achieved stable disease (median duration 3.4 months). As a result, the study was closed at the end of the first stage. Grades 3-4 neutropenia and thrombocytopenia were observed in 29% and 35%, respectively. There was no relationship between change in circulating endothelial cell numbers (CECs) and bidimensional tumor burden over time. Despite some activity in solid tumors, sunitinib showed no evidence of response in relapsed/refractory DLBCL and had greater than expected hematologic toxicity.

Sunitinib in relapsed or refractory diffuse large B-cell lymphoma: a clinical and pharmacodynamic phase II multicenter study of the NCIC Clinical Trials Group

PubMed Central

Buckstein, Rena; Kuruvilla, John; Chua, Neil; Lee, Christina; Macdonald, David A; Al-Tourah, Abdulwahab J; Foo, Alison H; Walsh, Wendy; Ivy, S Percy; Crump, Michael; Eisenhauer, Elizabeth A

2011-01-01

There are limited effective therapies for most patients with relapsed diffuse large B-cell lymphoma (DLBCL). We conducted a phase II trial of the multi-targeted vascular endothelial growth factor receptor (VEGFR) kinase inhibitor, sunitinib, 37.5 mg given orally once daily in adult patients with relapsed or refractory DLBCL. Of 19 enrolled patients, 17 eligible patients were evaluable for toxicity and 15 for response. No objective responses were seen and nine patients achieved stable disease (median duration 3.4 months). As a result, the study was closed at the end of the first stage. Grades 3—4 neutropenia and thrombocytopenia were observed in 29% and 35%, respectively. There was no relationship between change in circulating endothelial cell numbers (CECs) and bidimensional tumor burden over time. Despite some activity in solid tumors, sunitinib showed no evidence of response in relapsed/refractory DLBCL and had greater than expected hematologic toxicity. PMID:21463120

Report on the biological monitoring program at Paducah Gaseous Diffusion Plant December 1990 to November 1992

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

Kszos, L.A.

1994-03-01

On September 23, 1987, the Commonwealth of Kentucky Natural Resources and Environmental Protection Cabinet issued an Agreed Order that required the development of a Biological Monitoring Program (BMP) for the Paducah Gaseous Diffusion Plant (PGDP). Beginning in fall 1991, the Environmental Sciences Division (ESD) at Oak Ridge National Lab (ORNL) added data collection and report preparation to its responsibilities for the PGDP BMP. The BMP has been continued because it has proven to be extremely valuable in identifying those effluents with the potential for adversely affecting instream fauna, assessing the ecological health of receiving streams, guiding plans for remediation, andmore » protecting human health. In September 1992, a renewed permit was issued which requires toxicity monitoring of continuous and intermittent outfalls on a quarterly basis. The BMP for PGDP consists of three major tasks: (1) effluent and ambient toxicity monitoring, (2) bioaccumulation studies, and (3) ecological surveys of stream communities. This report includes ESD/ORNL activities occurring from December 1990 to November 1992.« less

Neurotoxic effects of ecstasy on the thalamus.

PubMed

de Win, Maartje M L; Jager, Gerry; Booij, Jan; Reneman, Liesbeth; Schilt, Thelma; Lavini, Cristina; Olabarriaga, Sílvia D; Ramsey, Nick F; Heeten, Gerard J den; van den Brink, Wim

2008-10-01

Neurotoxic effects of ecstasy have been reported, although it remains unclear whether effects can be attributed to ecstasy, other recreational drugs or a combination of these. To assess specific/independent neurotoxic effects of heavy ecstasy use and contributions of amphetamine, cocaine and cannabis as part of The Netherlands XTC Toxicity (NeXT) study. Effects of ecstasy and other substances were assessed with (1)H-magnetic resonance spectroscopy, diffusion tensor imaging, perfusion weighted imaging and [(123)I]2beta-carbomethoxy-3beta-(4-iodophenyl)-tropane ([(123)I]beta-CIT) single photon emission computed tomography (serotonin transporters) in a sample (n=71) with broad variation in drug use, using multiple regression analyses. Ecstasy showed specific effects in the thalamus with decreased [(123)I]beta-CIT binding, suggesting serotonergic axonal damage; decreased fractional anisotropy, suggesting axonal loss; and increased cerebral blood volume probably caused by serotonin depletion. Ecstasy had no effect on brain metabolites and apparent diffusion coefficients. Converging evidence was found for a specific toxic effect of ecstasy on serotonergic axons in the thalamus.

Biocompatible polymer microneedle for topical/dermal delivery of tranexamic acid.

PubMed

A Machekposhti, S; Soltani, M; Najafizadeh, P; Ebrahimi, S A; Chen, P

2017-09-10

Recently-introduced biocompatible polymeric microneedles offer an efficient method for drug delivery. Tranexamic acid is a novel drug for treating melasma that is administered both locally and orally and inhibits excessive melanin via melanocyte. The tranexamic acid biocompatible polymer microneedle used in this study was fabricated from PVP and methacrylic acid, using the lithography method. The required mechanical strength to pierce skin was attained by optimizing the ratio of PVP to methacrylic acid. Acute dermal toxicity was done, and drug diffusion in skin layers was simulated by calculating the diffusion coefficient of tranexamic acid in interstitial fluid (plasma). The biocompatible polymer microneedle was fabricated at 60°C. Needles could sustain 0.6N that is enough to pierce stratum corneum. 34% of the released drug was locally effective and the rest permeated through the skin. The pyramidal polymer microneedle in this study was fully released in skin in approx. 7h. This polymer microneedle has no dermal toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Diffuse Scattering as an Aid to the Understanding of Polymorphism in Pharmaceuticals

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

Welberry, T.R.; Chan, E.J.; Goossens, D.J.

Polymorphism occurs when the same molecular compound can crystallize in more than one distinct crystal structure. Its study is a field of great interest and activity. This is largely driven by its importance in the pharmaceutical industry, but polymorphism is also an issue in the pigments, dyes, and explosives industries. The polymorph formed by a compound generally exerts a strong influence on its solid-state properties. The polymorphic form of a drug molecule may affect the ease of manufacture and processing, shelf life, and most significantly the rate of uptake of the molecule by the human body. They can even varymore » in toxicity; one polymorph may be safe, while a second may be toxic. In this review of recently published work, we show how diffuse scattering experiments coupled with Monte Carlo (MC) computer modeling can aid in the understanding of polymorphism. Examples of the two common pharmaceuticals, benzocaine and aspirin, both of which are bimorphic, at ambient temperatures, are discussed.« less

Diffuse Scattering as an Aid to the Understanding of Polymorphism in Pharmaceuticals

NASA Astrophysics Data System (ADS)

Welberry, T. R.; Chan, E. J.; Goossens, D. J.; Heerdegen, A. P.

2012-05-01

Polymorphism occurs when the same molecular compound can crystallize in more than one distinct crystal structure. Its study is a field of great interest and activity. This is largely driven by its importance in the pharmaceutical industry, but polymorphism is also an issue in the pigments, dyes, and explosives industries. The polymorph formed by a compound generally exerts a strong influence on its solid-state properties. The polymorphic form of a drug molecule may affect the ease of manufacture and processing, shelf life, and most significantly the rate of uptake of the molecule by the human body. They can even vary in toxicity; one polymorph may be safe, while a second may be toxic. In this review of recently published work, we show how diffuse scattering experiments coupled with Monte Carlo (MC) computer modeling can aid in the understanding of polymorphism. Examples of the two common pharmaceuticals, benzocaine and aspirin, both of which are bimorphic, at ambient temperatures, are discussed.

[Cognitive impairment in a toxic lesion of the brain].

PubMed

Katamanova, E V; Rukavishnikov, V S; Lakhman, O L; Shevchenko, O I; Denisova, I A

2015-01-01

To identify features of cognitive impairment in patients with toxic (mercury or alcohol) encephalopathy. The study involved 36 patients with chronic mercury intoxication and 30 people with chronic alcoholism. A control group included 30 age-matched healthy men who were not exposed to toxic substances and alcohol abuse. All patients underwent neuropsychological examination, which involved a set of neuropsychological Luria rated memory status, praxis, gnosis and speeches. MMSE and FAB were used for the diagnosis of moderate cognitive impairment. Computer electroencephalography and cognitive evoked potentials method were used as well. The diffuse brain injury in toxic encephalopathy (alcohol and mercury) on EEG, and according to the results of neuropsychological testing was identified. Changes in analytical and synthetic thinking, audio-verbal, long-term, visual memory, reciprocal coordination, finger gnosis, impressive speech were observed in mercury encephalopathy. Functional failure of the frontal lobe and the premotor area of the left hemisphere were revealed in alcoholic encephalopathy.

Spatial and temporal trends of selected trace elements in liver tissue from polar bears (Ursus maritimus) from Alaska, Canada and Greenland.

PubMed

Routti, Heli; Letcher, Robert J; Born, Erik W; Branigan, Marsha; Dietz, Rune; Evans, Thomas J; Fisk, Aaron T; Peacock, Elizabeth; Sonne, Christian

2011-08-01

Spatial trends and comparative changes in time of selected trace elements were studied in liver tissue from polar bears from ten different subpopulation locations in Alaska, Canadian Arctic and East Greenland. For nine of the trace elements (As, Cd, Cu, Hg, Mn, Pb, Rb, Se and Zn) spatial trends were investigated in 136 specimens sampled during 2005-2008 from bears from these ten subpopulations. Concentrations of Hg, Se and As were highest in the (northern and southern) Beaufort Sea area and lowest in (western and southern) Hudson Bay area and Chukchi/Bering Sea. In contrast, concentrations of Cd showed an increasing trend from east to west. Minor or no spatial trends were observed for Cu, Mn, Rb and Zn. Spatial trends were in agreement with previous studies, possibly explained by natural phenomena. To assess temporal changes of Cd, Hg, Se and Zn concentrations during the last decades, we compared our results to previously published data. These time comparisons suggested recent Hg increase in East Greenland polar bears. This may be related to Hg emissions and/or climate-induced changes in Hg cycles or changes in the polar bear food web related to global warming. Also, Hg:Se molar ratio has increased in East Greenland polar bears, which suggests there may be an increased risk for Hg(2+)-mediated toxicity. Since the underlying reasons for spatial trends or changes in time of trace elements in the Arctic are still largely unknown, future studies should focus on the role of changing climate and trace metal emissions on geographical and temporal trends of trace elements.

Spatial and temporal trends of selected trace elements in liver tissue from polar bears (Ursus maritimus) from Alaska, Canada and Greenland

USGS Publications Warehouse

Routti, H.; Letcher, R.J.; Born, E.W.; Branigan, M.; Dietz, R.; Evans, T.J.; Fisk, A.T.; Peacock, E.; Sonne, C.

2011-01-01

Spatial trends and comparative changes in time of selected trace elements were studied in liver tissue from polar bears from ten different subpopulation locations in Alaska, Canadian Arctic and East Greenland. For nine of the trace elements (As, Cd, Cu, Hg, Mn, Pb, Rb, Se and Zn) spatial trends were investigated in 136 specimens sampled during 2005-2008 from bears from these ten subpopulations. Concentrations of Hg, Se and As were highest in the (northern and southern) Beaufort Sea area and lowest in (western and southern) Hudson Bay area and Chukchi/Bering Sea. In contrast, concentrations of Cd showed an increasing trend from east to west. Minor or no spatial trends were observed for Cu, Mn, Rb and Zn. Spatial trends were in agreement with previous studies, possibly explained by natural phenomena. To assess temporal changes of Cd, Hg, Se and Zn concentrations during the last decades, we compared our results to previously published data. These time comparisons suggested recent Hg increase in East Greenland polar bears. This may be related to Hg emissions and/or climate-induced changes in Hg cycles or changes in the polar bear food web related to global warming. Also, Hg:Se molar ratio has increased in East Greenland polar bears, which suggests there may be an increased risk for Hg 2+-mediated toxicity. Since the underlying reasons for spatial trends or changes in time of trace elements in the Arctic are still largely unknown, future studies should focus on the role of changing climate and trace metal emissions on geographical and temporal trends of trace elements. ?? 2011 The Royal Society of Chemistry.

Acute pancreatitis associated with administration of a nitric oxide synthase inhibitor in tumor-bearing dogs.

PubMed

Poulson, J M; Dewhirst, M W; Gaskin, A A; Vujaskovic, Z; Samulski, T V; Prescott, D M; Meyer, R E; Page, R L; Thrall, D E

2000-01-01

Nitric oxide synthase (NOS) inhibitors have been investigated as potential cytotoxic agents to treat tumors lacking p53 function. Furthermore, their ability to reduce tumor blood flow can be combined with drugs that are specifically designed to kill cells that are hypoxic or to improve temperatures during local heat (hyperthermia) treatment of tumors. This paper reports the unexpected development of acute pancreatitis in two tumor-bearing pet dogs that were treated with the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) during administration of local hyperthermia. Prior to the use of L-NAME in tumor-bearing dogs, purpose-bred beagles were studied. Following induction of inhalation anesthesia, local hyperthermia was applied to either normal thigh muscle (beagles) or tumors (tumor-bearing dogs). Once a thermal steady state was achieved, L-NAME was administered and temperature monitoring continued. Animals were observed after treatment for evidence of toxicity. The beagles tolerated the treatment well, with no side effects noted either clinically or by routine CBC or blood chemistry analyses. In contrast, the first two tumor-bearing dogs accrued onto the phase I study developed acute pancreatitis in the immediate post-treatment period which necessitated hospitalization and intensive care. The trial was stopped. Both dogs had intercurrent risk factors which predisposed them to development of pancreatitis, although neither had a history of symptoms of pancreatitis at the time the hyperthermia + L-NAME treatment was given. We conclude that caution should be exercised when considering NOS inhibition for cancer treatment. Careful evaluation of history and health status as well as recognition of potential risk factors may be key in avoiding potentially fatal complications. This study demonstrates the value of performing potentially harmful treatments in tumor-bearing dogs prior to introduction into the human clinic.

High Technology Centrifugal Compressor for Commercial Air Conditioning Systems

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

Ruckes, John

2006-04-15

R&D Dynamics, Bloomfield, CT in partnership with the State of Connecticut has been developing a high technology, oil-free, energy-efficient centrifugal compressor called CENVA for commercial air conditioning systems under a program funded by the US Department of Energy. The CENVA compressor applies the foil bearing technology used in all modern aircraft, civil and military, air conditioning systems. The CENVA compressor will enhance the efficiency of water and air cooled chillers, packaged roof top units, and other air conditioning systems by providing an 18% reduction in energy consumption in the unit capacity range of 25 to 350 tons of refrigeration Themore » technical approach for CENVA involved the design and development of a high-speed, oil-free foil gas bearing-supported two-stage centrifugal compressor, CENVA encompassed the following high technologies, which are not currently utilized in commercial air conditioning systems: Foil gas bearings operating in HFC-134a; Efficient centrifugal impellers and diffusers; High speed motors and drives; and System integration of above technologies. Extensive design, development and testing efforts were carried out. Significant accomplishments achieved under this program are: (1) A total of 26 builds and over 200 tests were successfully completed with successively improved designs; (2) Use of foil gas bearings in refrigerant R134a was successfully proven; (3) A high speed, high power permanent magnet motor was developed; (4) An encoder was used for signal feedback between motor and controller. Due to temperature limitations of the encoder, the compressor could not operate at higher speed and in turn at higher pressure. In order to alleviate this problem a unique sensorless controller was developed; (5) This controller has successfully been tested as stand alone; however, it has not yet been integrated and tested as a system; (6) The compressor successfully operated at water cooled condensing temperatures Due to temperature limitations of the encoder, it could not be operated at air cooled condensing temperatures. (7) The two-stage impellers/diffusers worked well separately but combined did not match well.« less

Finite Volume Scheme for Double Convection-Diffusion Exchange of Solutes in Bicarbonate High-Flux Hollow-Fiber Dialyzer Therapy

PubMed Central

Annan, Kodwo

2012-01-01

The efficiency of a high-flux dialyzer in terms of buffering and toxic solute removal largely depends on the ability to use convection-diffusion mechanism inside the membrane. A two-dimensional transient convection-diffusion model coupled with acid-base correction term was developed. A finite volume technique was used to discretize the model and to numerically simulate it using MATLAB software tool. We observed that small solute concentration gradients peaked and were large enough to activate solute diffusion process in the membrane. While CO2 concentration gradients diminished from their maxima and shifted toward the end of the membrane, HCO3 − concentration gradients peaked at the same position. Also, CO2 concentration decreased rapidly within the first 47 minutes while optimal HCO3 − concentration was achieved within 30 minutes of the therapy. Abnormally high diffusion fluxes were observed near the blood-membrane interface that increased diffusion driving force and enhanced the overall diffusive process. While convective flux dominated total flux during the dialysis session, there was a continuous interference between convection and diffusion fluxes that call for the need to seek minimal interference between these two mechanisms. This is critical for the effective design and operation of high-flux dialyzers. PMID:23197994

Toxicity assessment of metoprolol and its photodegradation mixtures obtained by using different type of TiO2 catalysts in the mammalian cell lines.

PubMed

Četojević-Simin, Dragana D; Armaković, Sanja J; Šojić, Daniela V; Abramović, Biljana F

2013-10-01

Toxicity of metoprolol (MET) alone and in mixtures with its photocatalytic degradation intermediates obtained by using TiO2 Wackherr and Degussa P25 under UV irradiation in the presence of O2 was evaluated in vitro in a panel of three histologically different cell lines: rat hepatoma (H-4-II-E), human colon adenocarcinoma (HT-29) and human fetal lung (MRC-5). Both catalysts promoted a time-dependent increase in the toxicity of the photodegradation products, and those obtained using Degussa P25 photocatalyst were more toxic. The most pronounced and selective toxic action of MET and products of its photodegradation was observed in the hepatic cell line. The higher toxicity of the mixtures obtained using Degussa P25 catalyst could be explained by a different mechanism of MET degradation, i.e. by the presence or higher concentrations of some intermediates. Although the concentrations of intermediates obtained using TiO2 Wackherr catalyst were higher, they did not affect significantly the growth of the examined cell lines, indicating their lower toxicity. This suggests that a treatment aiming at complete mineralization should be performed bearing in mind that the type of catalyst, the concentration of target molecule, and the duration of the process are significant factors that determine the nature and toxicity of the resulting mixtures. Although the EC50 values of MET obtained in mammalian cell lines were higher compared to the bioassays for lower trophic levels, the time-dependent promotion of toxicity of degradation mixtures should be attributed to the higher sensitivity of mammalian cell bioassays. © 2013 Elsevier B.V. All rights reserved.

The Eye Drop Preservative Benzalkonium Chloride Potently Induces Mitochondrial Dysfunction and Preferentially Affects LHON Mutant Cells.

PubMed

Datta, Sandipan; Baudouin, Christophe; Brignole-Baudouin, Francoise; Denoyer, Alexandre; Cortopassi, Gino A

2017-04-01

Benzalkonium chloride (BAK) is the most commonly used eye drop preservative. Benzalkonium chloride has been associated with toxic effects such as "dry eye" and trabecular meshwork degeneration, but the underlying biochemical mechanism of ocular toxicity by BAK is unclear. In this study, we propose a mechanistic basis for BAK's adverse effects. Mitochondrial O2 consumption rates of human corneal epithelial primary cells (HCEP), osteosarcoma cybrid cells carrying healthy (control) or Leber hereditary optic neuropathy (LHON) mutant mtDNA [11778(G>A)], were measured before and after acute treatment with BAK. Mitochondrial adenosine triphosphate (ATP) synthesis and cell viability were also measured in the BAK-treated control: LHON mutant and human-derived trabecular meshwork cells (HTM3). Benzalkonium chloride inhibited mitochondrial ATP (IC50, 5.3 μM) and O2 consumption (IC50, 10.9 μM) in a concentration-dependent manner, by directly targeting mitochondrial complex I. At its pharmaceutical concentrations (107-667 μM), BAK inhibited mitochondrial function >90%. In addition, BAK elicited concentration-dependent cytotoxicity to cybrid cells (IC50, 22.8 μM) and induced apoptosis in HTM3 cells at similar concentrations. Furthermore, we show that BAK directly inhibits mitochondrial O2 consumption in HCEP cells (IC50, 3.8 μM) at 50-fold lower concentrations than used in eye drops, and that cells bearing mitochondrial blindness (LHON) mutations are further sensitized to BAK's mitotoxic effect. Benzalkonium chloride inhibits mitochondria of human corneal epithelial cells and cells bearing LHON mutations at pharmacologically relevant concentrations, and we suggest this is the basis of BAK's ocular toxicity. Prescribing BAK-containing eye drops should be avoided in patients with mitochondrial deficiency, including LHON patients, LHON carriers, and possibly primary open-angle glaucoma patients.

The Eye Drop Preservative Benzalkonium Chloride Potently Induces Mitochondrial Dysfunction and Preferentially Affects LHON Mutant Cells

PubMed Central

Datta, Sandipan; Baudouin, Christophe; Brignole-Baudouin, Francoise; Denoyer, Alexandre; Cortopassi, Gino A.

2017-01-01

Purpose Benzalkonium chloride (BAK) is the most commonly used eye drop preservative. Benzalkonium chloride has been associated with toxic effects such as “dry eye” and trabecular meshwork degeneration, but the underlying biochemical mechanism of ocular toxicity by BAK is unclear. In this study, we propose a mechanistic basis for BAK's adverse effects. Method Mitochondrial O2 consumption rates of human corneal epithelial primary cells (HCEP), osteosarcoma cybrid cells carrying healthy (control) or Leber hereditary optic neuropathy (LHON) mutant mtDNA [11778(G>A)], were measured before and after acute treatment with BAK. Mitochondrial adenosine triphosphate (ATP) synthesis and cell viability were also measured in the BAK-treated control: LHON mutant and human-derived trabecular meshwork cells (HTM3). Results Benzalkonium chloride inhibited mitochondrial ATP (IC50, 5.3 μM) and O2 consumption (IC50, 10.9 μM) in a concentration-dependent manner, by directly targeting mitochondrial complex I. At its pharmaceutical concentrations (107–667 μM), BAK inhibited mitochondrial function >90%. In addition, BAK elicited concentration-dependent cytotoxicity to cybrid cells (IC50, 22.8 μM) and induced apoptosis in HTM3 cells at similar concentrations. Furthermore, we show that BAK directly inhibits mitochondrial O2 consumption in HCEP cells (IC50, 3.8 μM) at 50-fold lower concentrations than used in eye drops, and that cells bearing mitochondrial blindness (LHON) mutations are further sensitized to BAK's mitotoxic effect. Conclusions Benzalkonium chloride inhibits mitochondria of human corneal epithelial cells and cells bearing LHON mutations at pharmacologically relevant concentrations, and we suggest this is the basis of BAK's ocular toxicity. Prescribing BAK-containing eye drops should be avoided in patients with mitochondrial deficiency, including LHON patients, LHON carriers, and possibly primary open-angle glaucoma patients. PMID:28444329

Neural stem cell-mediated enzyme/prodrug therapy for glioma: preclinical studies.

PubMed

Aboody, Karen S; Najbauer, Joseph; Metz, Marianne Z; D'Apuzzo, Massimo; Gutova, Margarita; Annala, Alexander J; Synold, Timothy W; Couture, Larry A; Blanchard, Suzette; Moats, Rex A; Garcia, Elizabeth; Aramburo, Soraya; Valenzuela, Valerie V; Frank, Richard T; Barish, Michael E; Brown, Christine E; Kim, Seung U; Badie, Behnam; Portnow, Jana

2013-05-08

High-grade gliomas are extremely difficult to treat because they are invasive and therefore not curable by surgical resection; the toxicity of current chemo- and radiation therapies limits the doses that can be used. Neural stem cells (NSCs) have inherent tumor-tropic properties that enable their use as delivery vehicles to target enzyme/prodrug therapy selectively to tumors. We used a cytosine deaminase (CD)-expressing clonal human NSC line, HB1.F3.CD, to home to gliomas in mice and locally convert the prodrug 5-fluorocytosine to the active chemotherapeutic 5-fluorouracil. In vitro studies confirmed that the NSCs have normal karyotype, tumor tropism, and CD expression, and are genetically and functionally stable. In vivo biodistribution studies demonstrated NSC retention of tumor tropism, even in mice pretreated with radiation or dexamethasone to mimic clinically relevant adjuvant therapies. We evaluated safety and toxicity after intracerebral administration of the NSCs in non-tumor-bearing and orthotopic glioma-bearing immunocompetent and immunodeficient mice. We detected no difference in toxicity associated with conversion of 5-fluorocytosine to 5-fluorouracil, no NSCs outside the brain, and no histological evidence of pathology or tumorigenesis attributable to the NSCs. The average tumor volume in mice that received HB1.F3.CD NSCs and 5-fluorocytosine was about one-third that of the average volume in control mice. On the basis of these results, we conclude that combination therapy with HB1.F3.CD NSCs and 5-fluorocytosine is safe, nontoxic, and effective in mice. These data have led to approval of a first-in-human study of an allogeneic NSC-mediated enzyme/prodrug-targeted cancer therapy in patients with recurrent high-grade glioma.

Antitumor activity and systemic effects of PVM/MA-shelled selol nanocapsules in lung adenocarcinoma-bearing mice

NASA Astrophysics Data System (ADS)

de Souza, Ludmilla Regina; Alexandre Muehlmann, Luis; Carneiro Matos, Lívia; Simón-Vázquez, Rosana; Guerreiro Marques Lacava, Zulmira; Maurício Batista De-Paula, Alfredo; Mosiniewicz-Szablewska, Ewa; Suchocki, Piotr; César Morais, Paulo; González-Fernández, África; Nair Báo, Sônia; Bentes Azevedo, Ricardo

2015-12-01

Selol is a semi-synthetic compound containing selenite that is effective against cancerous cells and safer for clinical applications in comparison with other inorganic forms of selenite. Recently, we have developed a formulation of poly(methyl vinyl ether-co-maleic anhydride)-shelled selol nanocapsules (SPN), which reduced the proliferative activity of lung adenocarcinoma cells and presented little deleterious effects on normal cells in in vitro studies. In this study, we report on the antitumor activity and systemic effects induced by this formulation in chemically induced lung adenocarcinoma-bearing mice. The in vivo antitumor activity of the SPN was verified by macroscopic quantification, immunohistochemistry and morphological analyses. Toxicity analyses were performed by evaluations of the kidney, liver, and spleen; analyses of hemogram and plasma levels of alanine aminotransferase, aspartate transaminase, urea, and creatinine; and DNA fragmentation and cell cycle activity of the bone marrow cells. Furthermore, we investigated the potential of the SPN formulation to cause hemolysis, activate the complement system, provoke an inflammatory response and change the conformation of the plasma proteins. Our results showed that the SPN reduced the area of the surface tumor nodules but not the total number of tumor nodules. The biochemical and hematological findings were suggestive of the low systemic toxicity of the SPN formulation. The surface properties of the selol nanocapsules point to characteristics that are consistent with the treatment of the tumors in vivo: low hemolytic activity, weak inflammatory reaction with no activation of the complement system, and mild or absent conformational changes of the plasma proteins. In conclusion, this report suggests that the SPN formulation investigated herein exhibits anti-tumoral effects against lung adenocarcinoma in vivo and is associated with low systemic toxicity and high biocompatibility.

Exposure-dependent incorporation of trifluridine into DNA of tumors and white blood cells in tumor-bearing mouse.

PubMed

Yamashita, Fumiaki; Komoto, Ikumi; Oka, Hiroaki; Kuwata, Keizo; Takeuchi, Mayuko; Nakagawa, Fumio; Yoshisue, Kunihiro; Chiba, Masato

2015-08-01

Trifluridine (TFT) is an antitumor component of a novel nucleoside antitumor agent, TAS-102, which consists of TFT and tipiracil hydrochloride (thymidine phosphorylase inhibitor). Incorporation of TFT into DNA is a probable mechanism of antitumor activity and hematological toxicity. The objective of this study was to examine the TFT incorporation into tumor- and white blood cell-DNA, and to elucidate the mechanism of TFT-related effect and toxicity. TFT effect on the colony formation of mouse bone marrow cells was also investigated. Pharmacokinetics of TFT was determined in nude mice after single oral administration of TAS-102, while the antitumor activity and body weight change were evaluated in the tumor-bearing nude mice after multiple oral administrations for 2 weeks. TFT concentrations in the blood- and tumor-DNA were determined by LC/MS/MS. The colony formation was evaluated by CFU-GM assay. TFT systemic exposure in plasma increased dose-dependently. The tumor growth rate and body weight gain decreased dose-dependently, but TFT concentrations in the DNA of tumor tissues and white blood cells increased dose-dependently. TFT inhibited colony formation of bone marrow cells in a concentration-dependent manner. A significant relationship between systemic exposure of TFT and pharmacological effects including the antitumor activity and body weight change was well explained by the TFT incorporation into DNA. TFT inhibited proliferations of mouse bone marrow cells and human colorectal carcinoma cells implanted to nude mice dose-dependently. The highest tolerable TFT exposure provides the highest antitumor activity, and the hematological toxicity may serve as a potential surrogate indicator of TAS-102 efficacy.

Charge Effect on the Formation of Polyoxometalate-Based Supramolecular Polygons Driven by Metal Coordination.

PubMed

Piot, Madeleine; Hupin, Sébastien; Lavanant, Hélène; Afonso, Carlos; Bouteiller, Laurent; Proust, Anna; Izzet, Guillaume

2017-07-17

The metal-driven self-assembly of a Keggin-based hybrid bearing two remote pyridine units was investigated. The resulting supramolecular species were identified by combination of 2D diffusion NMR spectroscopy (DOSY) and electrospray ionization mass spectrometry (ESI-MS) as a mixture of molecular triangles and squares. This behavior is different from that of the structural analogue Dawson-based hybrid displaying a higher charge, which only led to the formation of molecular triangles. This study highlights the decisive effect of the charge of the POMs in their self-assembly processes that disfavors the formation of large assemblies. An isothermal titration calorimetry (ITC) experiment confirmed the stronger binding in the case of the Keggin hybrids. A correlation between the diffusion coefficient D and the molecular mass M of the POM-based building block and its coordination oligomers was also observed. We show that the diffusion coefficient of these compounds is mainly determined by their occupied volume rather than by their shape.

Exsolution lamellae as fast diffusion pathways in rutile: implications for U-Pb thermochronology and Zr thermometry

NASA Astrophysics Data System (ADS)

Smye, A.; Seman, S.; Roberts, N. M. W.; Condon, D. J.; Davis, B.

2017-12-01

Geophysical processes impart characteristic thermal signatures to the lithosphere. Near-continuous thermal histories can be obtained from inversion of intracrystalline U-Pb age profiles in rutile and apatite provided that it can be shown that profile formed in response to Fickian-type diffusion. Here, we present the results of a combined LA-ICPMS and ID-TIMS U-Pb study on rutile grains from two garnet-bearing granulite xenoliths from a kimberlite in the Archean Slave province. Interpreted using numerical models, we show that the rutile U-Pb isotope systematics are consistent with slow-cooling following crystallization at 1.2 Ga, contemporaneous with the Mackenzie dike swarm. However, inversion of rutile U-Pb age gradients is complicated by the ubiquitous presence of ilmenite exsolution lamellae. We show that these lamellae act as fast diffusion pathways for Pb and High Field Strength Elements, including Zr. This has important implications for the use of rutile as a U-Pb themochronometer and as a single-phase thermometer.

Diffusion of herbicides through plastic film

USGS Publications Warehouse

Bridges, W.R.; Sanders, Herman O.

1963-01-01

Plastic film have been used by fishery workers as barriers to subdivide experimental ponds in order to assess the value of some chemical treatment, and as test vessels to contain dilute solutions or suspensions of toxic chemicals in experiments conducted to establish tolerance levels of these chemicals for fish.

A toxicity cost function approach to optimal CPA equilibration in tissues.

PubMed

Benson, James D; Higgins, Adam Z; Desai, Kunjan; Eroglu, Ali

2018-02-01

There is growing need for cryopreserved tissue samples that can be used in transplantation and regenerative medicine. While a number of specific tissue types have been successfully cryopreserved, this success is not general, and there is not a uniform approach to cryopreservation of arbitrary tissues. Additionally, while there are a number of long-established approaches towards optimizing cryoprotocols in single cell suspensions, and even plated cell monolayers, computational approaches in tissue cryopreservation have classically been limited to explanatory models. Here we develop a numerical approach to adapt cell-based CPA equilibration damage models for use in a classical tissue mass transport model. To implement this with real-world parameters, we measured CPA diffusivity in three human-sourced tissue types, skin, fibroid and myometrium, yielding propylene glycol diffusivities of 0.6 × 10 -6  cm 2 /s, 1.2 × 10 -6  cm 2 /s and 1.3 × 10 -6  cm 2 /s, respectively. Based on these results, we numerically predict and compare optimal multistep equilibration protocols that minimize the cell-based cumulative toxicity cost function and the damage due to excessive osmotic gradients at the tissue boundary. Our numerical results show that there are fundamental differences between protocols designed to minimize total CPA exposure time in tissues and protocols designed to minimize accumulated CPA toxicity, and that "one size fits all" stepwise approaches are predicted to be more toxic and take considerably longer than needed. Copyright © 2017 Elsevier Inc. All rights reserved.

Selective uptake of multi-walled carbon nanotubes by tumor macrophages in a murine glioma model.

PubMed

VanHandel, Michelle; Alizadeh, Darya; Zhang, Leying; Kateb, Babak; Bronikowski, Michael; Manohara, Harish; Badie, Behnam

2009-03-31

Carbon nantotubes (CNTs) are emerging as a new family of nanovectors for drug and gene delivery into biological systems. To evaluate potential application of this technology for brain tumor therapy, we studied uptake and toxicity of multi-walled CNTs (MWCNTs) in the GL261 murine intracranial glioma model. Within 24 h of a single intratumoral injection of labeled MWCNTs (5 microg), nearly 10-20% of total cells demonstrated CNT internalization. Most CNT uptake, however, occurred by tumor-associated macrophages (MP), which accounted for most (75%) MWCNT-positive cells. Within 24 h of injection, nearly 30% of tumor MP became MWCNT-positive. Despite a transient increase in inflammatory cell infiltration into both normal and tumor-bearing brains following MWCNT injection, no significant toxicity was noted in mice, and minor changes in tumor cytokine expression were observed. This study suggests that MWCNTs could potentially be used as a novel and non-toxic vehicle for targeting MP in brain tumors.

Stratiform chromite deposit model: Chapter E in Mineral deposit models for resource assessment

USGS Publications Warehouse

Schulte, Ruth F.; Taylor, Ryan D.; Piatak, Nadine M.; Seal, Robert R.

2012-01-01

Most environmental concerns associated with the mining and processing of chromite ore focus on the solubility of chromium and its oxidation state. Although trivalent chromium (Cr3+) is an essential micronutrient for humans, hexavalent chromium (Cr6+) is highly toxic. Chromium-bearing solid phases that occur in the chromite ore-processing residue, for example, can effect the geochemical behavior and oxidation state of chromium in the environment.

Influence of enamel/dentin thickness on the toxic and esthetic effects of experimental in-office bleaching protocols.

PubMed

de Oliveira Duque, C C; Soares, D G; Basso, F G; Hebling, J; de Souza Costa, C A

2017-11-01

This paper aims to assess the whitening effectiveness and toxicity of tooth-bleaching protocols applied to enamel/dentin disks simulating mandibular incisors (ICs) and premolars (PMs). A 10% hydrogen peroxide (H 2 O 2 ) gel was applied for 3 × 15, 1 × 15, or 1 × 5 min to enamel/dentin disks simulating mandibular ICs and PMs, and the trans-enamel and trans-dentinal diffusion products were applied to human dental pulp cells (1 h). Professional therapy (35% H 2 O 2 -3 × 15 min) was used as positive control, and non-bleached samples were used as negative control. Cell viability and morphology, oxidative stress generation, and odontoblastic marker expression were assessed. The H 2 O 2 diffusion and enamel color change (ΔE) were also analyzed. The 10% H 2 O 2 gel induced significant cell viability reduction only when applied 3 × 15 min, with the intensity of oxidative stress and down-regulation of odontoblastic markers being higher in the IC group. The other experimental bleaching protocols caused slight alterations regarding the cell parameters evaluated, with intensity being related to enamel/dentin thickness. These effects were also correlated with higher H 2 O 2 diffusion in the IC group. ΔE values similar as positive control were found for the 10% 3 × 15 and 1 × 15 protocols on IC group, after 4 and 6 sessions. Application of a 10% H 2 O 2 bleaching gel for 15 or 45 min to thin dental substrate significantly minimizes cell toxicity in comparison with highly concentrated gels associated with similar esthetic outcomes by increasing the number of bleaching sessions. Bleaching gels with 10% H 2 O 2 applied in small teeth for short periods may be an interesting alternative to obtain whitening effectiveness without causing toxicity to pulp cells, which may be able to reduce the tooth hypersensitivity claimed by patients.

Evaluation of hepatic biotransformation of polybrominated diphenyl ethers in the polar bear (Ursus maritimus).

PubMed

Krieger, Lisa K; Szeitz, András; Bandiera, Stelvio M

2016-03-01

Polar bears are at the top of the Arctic marine food chain and are subject to exposure and bioaccumulation of environmental chemicals of concern such as polybrominated diphenyl ethers (PBDEs), which were widely used as flame retardants. The aim of the present study was to evaluate the in vitro oxidative metabolism of 2,2',4,4'-tetrabrominated diphenyl ether (BDE-47) and 2,2',4,4',5-pentabrominated diphenyl ether (BDE-99) by polar bear liver microsomes. The identification and quantification of the hydroxy-brominated diphenyl ethers formed were assessed using an ultra-high performance liquid chromatography-tandem mass spectrometry-based method. Incubation of BDE-47 with archived individual liver microsomes, prepared from fifteen polar bears from northern Canada, produced a total of eleven hydroxylated metabolites, eight of which were identified using authentic standards. The major metabolites were 4'-hydroxy-2,2',4,5'-tetrabromodiphenyl ether and 5'-hydroxy-2,2',4,4'-tetrabromodiphenyl ether. Incubation of BDE-99 with polar bear liver microsomes produced a total of eleven hydroxylated metabolites, seven of which were identified using authentic standards. The major metabolites were 2,4,5-tribromophenol and 4-hydroxy-2,2',3,4',5-pentabromodiphenyl ether. Among the CYP specific antibodies tested, anti-rat CYP2B was found to be the most active in inhibiting the formation of hydroxylated metabolites of both BDE-47 and BDE-99, indicating that CYP2B was the major CYP enzyme involved in the oxidative biotransformation of these two congeners. Our study shows that polar bears are capable of forming multiple hydroxylated metabolites of BDE-47 and BDE-99 in vitro and demonstrates the role of CYP2B in the biotransformation and possibly in the toxicity of BDE-47 and BDE-99 in polar bears. Copyright © 2015 Elsevier Ltd. All rights reserved.

Spectral reflectance properties (0.4-2.5 μm) of secondary Fe-oxide, Fe-hydroxide, and Fe-sulphate-hydrate minerals associated with sulphide-bearing mine wastes

USGS Publications Warehouse

Crowley, J.K.; Williams, D.E.; Hammarstrom, J.M.; Piatak, N.; Chou, I.-Ming; Mars, J.C.

2003-01-01

Diffuse reflectance spectra of 15 mineral species commonly associated with sulphide-bearing mine wastes show diagnostic absorption bands related to electronic processes involving ferric and/or ferrous iron, and to vibrational processes involving water and hydroxyl. Many of these absorption bands are relatively broad and overlapping; however, spectral analysis methods, including continuum removal and derivative analysis, permit most of the minerals to be distinguished. Key spectral differences between the minerals are illustrated in a series of plots showing major absorption band centres and other spectral feature positions. Because secondary iron minerals are sensitive indicators of pH, Eh, relative humidity, and other environmental conditions, spectral mapping of mineral distributions promises to have important application to mine waste remediation studies.

Two-photon NADH imaging exposes boundaries of oxygen diffusion in cortical vascular supply regions

PubMed Central

Kasischke, Karl A; Lambert, Elton M; Panepento, Ben; Sun, Anita; Gelbard, Harris A; Burgess, Robert W; Foster, Thomas H; Nedergaard, Maiken

2011-01-01

Oxygen transport imposes a possible constraint on the brain's ability to sustain variable metabolic demands, but oxygen diffusion in the cerebral cortex has not yet been observed directly. We show that concurrent two-photon fluorescence imaging of endogenous nicotinamide adenine dinucleotide (NADH) and the cortical microcirculation exposes well-defined boundaries of tissue oxygen diffusion in the mouse cortex. The NADH fluorescence increases rapidly over a narrow, very low pO2 range with a p50 of 3.4±0.6 mm Hg, thereby establishing a nearly binary reporter of significant, metabolically limiting hypoxia. The transient cortical tissue boundaries of NADH fluorescence exhibit remarkably delineated geometrical patterns, which define the limits of tissue oxygen diffusion from the cortical microcirculation and bear a striking resemblance to the ideal Krogh tissue cylinder. The visualization of microvessels and their regional contribution to oxygen delivery establishes penetrating arterioles as major oxygen sources in addition to the capillary network and confirms the existence of cortical oxygen fields with steep microregional oxygen gradients. Thus, two-photon NADH imaging can be applied to expose vascular supply regions and to localize functionally relevant microregional cortical hypoxia with micrometer spatial resolution. PMID:20859293

Two-photon NADH imaging exposes boundaries of oxygen diffusion in cortical vascular supply regions.

PubMed

Kasischke, Karl A; Lambert, Elton M; Panepento, Ben; Sun, Anita; Gelbard, Harris A; Burgess, Robert W; Foster, Thomas H; Nedergaard, Maiken

2011-01-01

Oxygen transport imposes a possible constraint on the brain's ability to sustain variable metabolic demands, but oxygen diffusion in the cerebral cortex has not yet been observed directly. We show that concurrent two-photon fluorescence imaging of endogenous nicotinamide adenine dinucleotide (NADH) and the cortical microcirculation exposes well-defined boundaries of tissue oxygen diffusion in the mouse cortex. The NADH fluorescence increases rapidly over a narrow, very low pO(2) range with a p(50) of 3.4 ± 0.6 mm Hg, thereby establishing a nearly binary reporter of significant, metabolically limiting hypoxia. The transient cortical tissue boundaries of NADH fluorescence exhibit remarkably delineated geometrical patterns, which define the limits of tissue oxygen diffusion from the cortical microcirculation and bear a striking resemblance to the ideal Krogh tissue cylinder. The visualization of microvessels and their regional contribution to oxygen delivery establishes penetrating arterioles as major oxygen sources in addition to the capillary network and confirms the existence of cortical oxygen fields with steep microregional oxygen gradients. Thus, two-photon NADH imaging can be applied to expose vascular supply regions and to localize functionally relevant microregional cortical hypoxia with micrometer spatial resolution.

Tractography of white matter based on diffusion tensor imaging in ischaemic stroke involving the corticospinal tract: a preliminary study

NASA Astrophysics Data System (ADS)

Zhong, Chongguang; Bai, Lijun; Cui, Fangyuan; Dai, Ruwei; Xue, Ting; Wang, Hu; Wei, Wenjuan; Liu, Zhenyu; You, Youbo; Zou, Yihuai; Tian, Jie

2012-03-01

Diffusion tensor MR imaging (DTI) provides information on diffusion anisotropy in vivo, which can be exhibited three-dimensional white matter tractography. Five healthy volunteers and five right-hand affected patients with early subacute ischaemic infarction involving the posterior limb of the internal capsule or corona radiate were recruited in this study. We used 3D white matter tractography to show the corticospinal tract in both volunteer group and stroke group. Then we compared parameters of the corticospinal tract in patients with that in normal subjects and assessed the relationships between the fiber number of the corticospinal tract in ipsilesional hemisphere and indicators of the patients' rehabilitation using Pearson correlation analysis. The fractional anisotropy (FA) values and apparent diffusion coefficient (ADC) values in the ipsilesional corticospinal tract may significantly reduce comparing with the volunteer group. In addition, the stroke patient with less fiber number of the ipsilesional corticospinal tract may bear more possibilities of better motor rehabilitation. The FA values, ADC values and fiber number of the corticospinal tract in the ipsilesional hemisphere might be helpful to the prognosis and prediction of clinical treatment in stroke patients.

Computational prediction of dermal diffusivity for large number of chemicals – challenges and applications

EPA Science Inventory

The assessment of risk from dermal exposure for thousands of chemicals, such as consumer products, due to their potential to enter the environment as contaminants is a daunting task. A strategy has been developed to integrate high-throughput technologies with toxicity, known as ...

Arsenic-transforming microbes and their role in biomining processes.

PubMed

Drewniak, L; Sklodowska, A

2013-11-01

It is well known that microorganisms can dissolve different minerals and use them as sources of nutrients and energy. The majority of rock minerals are rich in vital elements (e.g., P, Fe, S, Mg and Mo), but some may also contain toxic metals or metalloids, like arsenic. The toxicity of arsenic is disclosed after the dissolution of the mineral, which raises two important questions: (1) why do microorganisms dissolve arsenic-bearing minerals and release this metal into the environment in a toxic (also for themselves) form, and (2) How do these microorganisms cope with this toxic element? In this review, we summarize current knowledge about arsenic-transforming microbes and their role in biomining processes. Special consideration is given to studies that have increased our understanding of how microbial activities are linked to the biogeochemistry of arsenic, by examining (1) where and in which forms arsenic occurs in the mining environment, (2) microbial activity in the context of arsenic mineral dissolution and the mechanisms of arsenic resistance, (3) the minerals used and technologies applied in the biomining of arsenic, and (4) how microbes can be used to clean up post-mining environments.

Fatal toxic leukoencephalopathy secondary to overdose of a new psychoactive designer drug 2C-E ("Europa").

PubMed

Sacks, Justin; Ray, M Jordan; Williams, Sue; Opatowsky, Michael J

2012-10-01

We present a case of a fatal toxic leukoencephalopathy following ingestion of a new psychoactive designer drug known as 2C-E or "Europa." Recreational drugs, particularly hallucinogenic substances, appear to be growing in popularity, with increasing amounts of information available via the Internet to entice potential users. In addition, some newer "designer" psychoactive substances are available for purchase online without adverse legal consequences, therefore adding to their popularity. We describe magnetic resonance imaging (MRI) findings to include selective diffuse toxic injury of the cerebral white matter with sparing of the cortex and most of the deep gray nuclei. To our knowledge, this is the first reported description of cerebral findings on MRI that are likely related to a lethal ingestion of 2C-E.

Evaluating the cement stabilization of arsenic-bearing iron wastes from drinking water treatment.

PubMed

Clancy, Tara M; Snyder, Kathryn V; Reddy, Raghav; Lanzirotti, Antonio; Amrose, Susan E; Raskin, Lutgarde; Hayes, Kim F

2015-12-30

Cement stabilization of arsenic-bearing wastes is recommended to limit arsenic release from wastes following disposal. Such stabilization has been demonstrated to reduce the arsenic concentration in the Toxicity Characteristic Leaching Procedure (TCLP), which regulates landfill disposal of arsenic waste. However, few studies have evaluated leaching from actual wastes under conditions similar to ultimate disposal environments. In this study, land disposal in areas where flooding is likely was simulated to test arsenic release from cement stabilized arsenic-bearing iron oxide wastes. After 406 days submersed in chemically simulated rainwater, <0.4% of total arsenic was leached, which was comparable to the amount leached during the TCLP (<0.3%). Short-term (18 h) modified TCLP tests (pH 3-12) found that cement stabilization lowered arsenic leaching at high pH, but increased leaching at pH<4.2 compared to non-stabilized wastes. Presenting the first characterization of cement stabilized waste using μXRF, these results revealed the majority of arsenic in cement stabilized waste remained associated with iron. This distribution of arsenic differed from previous observations of calcium-arsenic solid phases when arsenic salts were stabilized with cement, illustrating that the initial waste form influences the stabilized form. Overall, cement stabilization is effective for arsenic-bearing wastes when acidic conditions can be avoided. Copyright © 2015 Elsevier B.V. All rights reserved.

Acute hepatic encephalopathy presenting as cortical laminar necrosis: case report.

PubMed

Choi, Jong Mun; Kim, Yoon Hee; Roh, Sook Young

2013-01-01

We report on a 55-year-old man with alcoholic liver cirrhosis who presented with status epilepticus. Laboratory analysis showed markedly elevated blood ammonia. Brain magnetic resonance imaging (MRI) showed widespread cortical signal changes with restricted diffusion, involving both temporo-fronto-parietal cortex, while the perirolandic regions and occipital cortex were uniquely spared. A follow-up brain MRI demonstrated diffuse cortical atrophy with increased signals on T1-weighted images in both the basal ganglia and temporal lobe cortex, representing cortical laminar necrosis. We suggest that the brain lesions, in our case, represent a consequence of toxic effect of ammonia.

Overview of major hazards. Part 2: Source term; dispersion; combustion; blast, missiles, venting; fire; radiation; runaway reactions; toxic substances; dust explosions

NASA Astrophysics Data System (ADS)

Vilain, J.

Approaches to major hazard assessment and prediction are reviewed. Source term: (phenomenology/modeling of release, influence on early stages of dispersion); dispersion (atmospheric advection, diffusion and deposition, emphasis on dense/cold gases); combustion (flammable clouds and mists covering flash fires, deflagration, transition to detonation; mostly unconfined/partly confined situations); blast formation, propagation, interaction with structures; catastrophic fires (pool fires, torches and fireballs; highly reactive substances) runaway reactions; features of more general interest; toxic substances, excluding toxicology; and dust explosions (phenomenology and protective measures) are discussed.

Design of an efficient space constrained diffuser for supercritical CO2 turbines

NASA Astrophysics Data System (ADS)

Keep, Joshua A.; Head, Adam J.; Jahn, Ingo H.

2017-03-01

Radial inflow turbines are an arguably relevant architecture for energy extraction from ORC and supercritical CO 2 power cycles. At small scale, design constraints can prescribe high exit velocities for such turbines, which lead to high kinetic energy in the turbine exhaust stream. The inclusion of a suitable diffuser in a radial turbine system allows some exhaust kinetic energy to be recovered as static pressure, thereby ensuring efficient operation of the overall turbine system. In supercritical CO 2 Brayton cycles, the high turbine inlet pressure can lead to a sealing challenge if the rotor is supported from the rotor rear side, due to the seal operating at rotor inlet pressure. An alternative to this is a cantilevered layout with the rotor exit facing the bearing system. While such a layout is attractive for the sealing system, it limits the axial space claim of any diffuser. Previous studies into conical diffuser geometries for supercritical CO 2 have shown that in order to achieve optimal static pressure recovery, longer geometries of a shallower cone angle are necessitated when compared to air. A diffuser with a combined annular-radial arrangement is investigated as a means to package the aforementioned geometric characteristics into a limited space claim for a 100kW radial inflow turbine. Simulation results show that a diffuser of this design can attain static pressure rise coefficients greater than 0.88. This confirms that annular-radial diffusers are a viable design solution for supercritical CO2 radial inflow turbines, thus enabling an alternative cantilevered rotor layout.

High-b-value diffusion-weighted MR imaging for pretreatment prediction and early monitoring of tumor response to therapy in mice.

PubMed

Roth, Yiftach; Tichler, Thomas; Kostenich, Genady; Ruiz-Cabello, Jesus; Maier, Stephan E; Cohen, Jack S; Orenstein, Arie; Mardor, Yael

2004-09-01

To evaluate the use of diffusion-weighted magnetic resonance (MR) imaging with standard and high b values for pretreatment prediction and early detection of tumor response to various antineoplastic therapies in an animal model. Mice bearing C26 colon carcinoma tumors were treated with doxorubicin (n = 25) and with aminolevulinic acid-based photodynamic therapy (n = 23). Fourteen mice served as controls. Conventional T2-weighted fast spin-echo and diffusion-weighted MR images were acquired once before therapy and at 6, 24, and 48 hours after treatment. Pretreatment and early (1-2 days) posttreatment water diffusion parameters were calculated and compared with later changes in tumor volumes measured on conventional MR images by using the Pearson correlation test. In chemotherapy-treated tumors, a significant correlation (P <.002, r = 0.6) was observed between diffusion parameters that reflected tumor viability, measured prior to treatment, and changes in tumor volumes after therapy. This correlation implies that tumors with high pretreatment viability will respond better to chemotherapy than more necrotic tumors. In tumors treated with photodynamic therapy, no such correlation was found. Changes observed in water diffusion 1-2 days after treatment significantly correlated with later tumor growth rate for both therapies (P <.002, r = 0.54 for photodynamic therapy; P <.0003, r = 0.61 for chemotherapy). High-b-value diffusion-weighted MR imaging has potential use for the early detection of response to therapy and for predicting treatment outcome prior to initiation of chemotherapy. Copyright RSNA, 2004

Preclinical development of a non-toxic oral formulation of monoethanolamine, a lipid precursor, for prostate cancer treatment

PubMed Central

Saxena, Roopali; Yang, Chunhua; Rao, Mukkavilli; Turaga, Ravi Chakra; Garlapati, Chakravarthy; Gundala, Sushma Reddy; Myers, Kimberly; Ghareeb, Ahmed; Bhattarai, Shristi; Kamilinia, Golnaz; Bristi, Sangina; Su, Dan; Gadda, Giovanni; Rida, Padmashree C. G.; Cantuaria, Guilherme H.; Aneja, Ritu

2018-01-01

Purpose Most currently-available chemotherapeutic agents target rampant cell division in cancer cells, thereby affecting rapidly-dividing normal cells resulting in toxic side-effects. This non-specificity necessitates identification of novel cellular pathways that are reprogrammed selectively in cancer cells and can be exploited to develop pharmacologically superior and less-toxic therapeutics. Despite growing awareness on dysregulation of lipid metabolism in cancer cells, targeting lipid biosynthesis is still largely uncharted territory. Herein, we report development of a novel non-toxic orally-deliverable anticancer formulation of monoethanolamine (Etn), for prostate cancer by targeting the Kennedy pathway of phosphatidylethanolamine (PE) lipid biosynthesis. Experimental Design We first evaluated GI-tract stability, drug-drug interaction liability, pharmacokinetic and toxicokinetic properties of Etn to evaluate its suitability as a non-toxic orally-deliverable agent. We next performed in vitro and in vivo experiments to investigate efficacy and mechanism of action. Results Our data demonstrate that Etn exhibits excellent bioavailability, GI-tract stability, and no drug-drug interaction liability. Remarkably, orally-fed Etn inhibited tumor growth in four weeks by ~67% in mice bearing human prostate cancer PC-3 xenografts without any apparent toxicity. Mechanistically, Etn exploits selective overexpression of choline kinase in cancer cells, resulting in accumulation of phosphoethanolamine (PhosE), accompanied by downregulation of HIF-1α that induces metabolic stress culminating into cell death. Conclusions Our study provides first evidence for the superior anticancer activity of Etn, a simple lipid precursor formulation, whose non-toxicity conforms to FDA-approved standards, compelling its clinical development for prostate cancer management. PMID:28167510

Copper speciation in variably toxic sediments at the Ely Copper Mine, Vermont, United States

USGS Publications Warehouse

Kimball, Bryn E.; Foster, Andrea L.; Seal, Robert R.; Piatak, Nadine M.; Webb, Samuel M.; Hammarstrom, Jane M.

2016-01-01

At the Ely Copper Mine Superfund site, Cu concentrations exceed background values in both streamwater (160–1200 times) and sediments (15–79 times). Previously, these sediment samples were incubated with laboratory test organisms, and they exhibited variable toxicity for different stream sites. In this study we combined bulk- and microscale techniques to determine Cu speciation and distribution in these contaminated sediments on the basis of evidence from previous work that Cu was the most important stressor in this environment and that variable observed toxicity could have resulted from differences in Cu speciation. Copper speciation results were similar at microscopic and bulk scales. The major Cu species in the more toxic samples were sorbed or coprecipitated with secondary Mn (birnessite) and Fe minerals (jarosite and goethite), which together accounted for nearly 80% of the total Cu. The major Cu species in the less toxic samples were Cu sulfides (chalcopyrite and a covellite-like phase), making up about 80–95% of the total Cu, with minor amounts of Cu associated with jarosite or goethite. These Cu speciation results are consistent with the toxicity results, considering that Cu sorbed or coprecipitated with secondary phases at near-neutral pH is relatively less stable than Cu bound to sulfide at lower pH. The more toxic stream sediment sites were those that contained fewer detrital sulfides and were upstream of the major mine waste pile, suggesting that removal and consolidation of sulfide-bearing waste piles on site may not eliminate all sources of bioaccessible Cu.

Buried homojunction in CdS/Sb2Se3 thin film photovoltaics generated by interfacial diffusion

NASA Astrophysics Data System (ADS)

Zhou, Ying; Li, Yang; Luo, Jiajun; Li, Dengbing; Liu, Xinsheng; Chen, Chao; Song, Huaibing; Ma, Jingyuan; Xue, Ding-Jiang; Yang, Bo; Tang, Jiang

2017-07-01

Antimony selenide (Sb2Se3) emerges as a very promising non-toxic absorber material for thin film photovoltaics, and most of the devices, either in the superstrate or substrate configuration, employed CdS as the buffer layer. Due to the peculiar one-dimensional crystal structure of Sb2Se3, severe interfacial diffusion would be expected. In this letter, the interfacial diffusion in CdS/Sb2Se3 photovoltaics was carefully characterized from a combined material and device physics characterization. The results indicated that a buried homojunction located deep inside the Sb2Se3 absorber layer due to Cd diffusion, instead of the apparent CdS/Sb2Se3 heterojunction, dictated charge separation and device performance in Sb2Se3 thin film solar cells. Cd diffusion converted p-type Sb2Se3 into n-type by introducing a donor level with an activation energy of 0.22 eV. Our studies deepen the understanding of Sb2Se3 photovoltaics and shed light on their further performance optimization.

Cross-reactivity and neutralization of Indian King cobra (Ophiophagus hannah) venom by polyvalent and monovalent antivenoms.

PubMed

Gowtham, Yashonandana J; Mahadeswaraswamy, Y H; Girish, K S; K, Kemparaju

2014-07-01

The venom of the largest venomous snake, the king cobra (Ophiophagus hannah), is still out of league for the production of therapeutic polyvalent antivenom nor it is characterized immunologically in the Indian subcontinent. In the present study, the king cobra venom is comparatively studied for the cross-reactivity/reactivity and toxicity neutralization by the locally available equine therapeutic polyvalent BSV and VB antivenoms, and monovalent antivenom (OH-IgG) prepared in rabbit. None of the two therapeutic antivenoms procured from two different firms showed any signs of cross-reactivity in terms of antigen-antibody precipitin lines in immunodouble diffusion assay; however, a weak and an insignificant cross-reactivity pattern was observed in ELISA and Western blot studies. Further, both BSV and VB antivenoms failed to neutralize proteolytic, hyaluronidase and phospholipase activities as well as toxic properties such as edema, myotoxicity and lethality of the venom. As expected, OH-IgG showed strong reactivity in immunodouble diffusion, ELISA and in Western blot analysis and also neutralized both enzyme activities as well as the toxic properties of the venom. Thus, the study provides insight into the likely measures that are to be taken in cases of accidental king cobra bites for which the Indian subcontinent is still not prepared for. Copyright © 2014 Elsevier B.V. All rights reserved.

Two reference time scales for studying the dynamic cavitation of liquid films

NASA Technical Reports Server (NTRS)

Sun, D. C.; Brewe, David E.

1991-01-01

Two formulas, one for characteristic time of filling a void with a vapor of the surrounding liquid, and one of filling the void by diffusion of the dissolved gas in the liquid, are derived. Based on this analysis, it is seen that in an oil film bearing operating under dynamic loads, the content of cavitation region should be oil vapor rather than the air liberated from solution, if the oil is free of entrained air.

LQFM030 reduced Ehrlich ascites tumor cell proliferation and VEGF levels.

PubMed

da Mota, Mariana Flavia; de Carvalho, Flávio Silva; de Ávila, Renato Ivan; de Ávila, Paulo Henrique Marcelino; Cortez, Alane Pereira; Menegatti, Ricardo; Sabino, José Ricardo; Dos Santos, Thais Rosa Marques; Gomes, Sandro Antônio; da Cunha, Luiz Carlos; Valadares, Marize Campos

2018-05-15

This study reports the biological properties of LQFM030 in vivo, a molecular simplification of the compound nutlin-1. Ehrlich ascites tumor (EAT)-bearing mice were treated intraperitoneally with LQFM030 (50, 75 or 150mg/kg) for 10days to determine changes in ascites tumor volume, body weight, cytotoxicity and angiogenesis. Moreover, flow cytometric expression of p53 and p21 proteins and caspase-3/7, -8 and -9 activation were investigated in EAT cells from mice treated. Acute oral systemic toxicity potential of LQFM030 in mice was also investigated using an alternative method. Treatment of EAT-bearing mice with LQFM030 resulted in a marked decline in tumor cell proliferation and the vascular endothelial growth factor (VEGF) levels along with enhanced survival of the mice. Apoptotic tumor cell death was detected through p53 and p21 modulation and increase of caspase-3/7, -8 and -9 activity. LQFM030 also showed orally well tolerated, being classified in the UN GHS category 5 (LD 50 >2000-5000mg/Kg). LQFM030 seems to be a promising antitumor candidate for combinatory therapy with typical cytotoxic compounds, reducing the toxicity burden while allowing a superior anticancer activity. Moreover, these data also open new perspectives for LQFM030 as an antiangiogenic agent for treatment of diseases involving VEGF overexpression. Copyright © 2017. Published by Elsevier Inc.

Two-Oxide Disequilibrium: A New Geospeedometer Based on Diffusion in Ilmenite

NASA Astrophysics Data System (ADS)

Williams, K. B.; Krawczynski, M. J.; Van Orman, J. A.

2016-12-01

Diffusion-annealing experiments were conducted in a 0.5" piston cylinder apparatus to investigate diffusivity of Fe2+, Mg2+, and Mn2+ in ilmenite solid solutions between 800ºC and 1000ºC. Polycrystalline ilmenite (FeTiO3) was juxtaposed against either an oriented geikielite (MgTiO3) single crystal or polycrystalline Mn-bearing (5 mol% Mn) ilmenite, in a "diffusion-couple" geometry. Geikielite single crystals were synthesized at Los Alamos National Laboratory, cut into 1 mm edge-length cubes, and polished either perpendicular or parallel to the c-axis. Polycrystalline ilmenite starting materials were synthesized by mixing high purity reagent-grade oxides (FeO, MnO, and TiO2) and sintering in a piston cylinder apparatus, then cut into wafers and polished. Experimental run products were analyzed by electron microprobe at Washington University in St. Louis. Microprobe analyses were obtained perpendicularly across the diffusion interface for each experiment. Experimental diffusion profiles create smooth curves that, when fit with an error function, define Fe-Mg and Fe-Mn interdiffusion coefficients in ilmenite. The diffusion coefficients do not appear compositionally dependent, but do show significant anisotropy. Preliminary results suggest diffusion activation energies are lower in ilmenite than in titanomagnetite [1]. Ilmenite-titanomagnetite equilibria define pre-eruptive temperatures and oxygen fugacities. However, oxides often exist out of equilibrium [2]. We use the cation diffusion data for ilmenite and existing data on titanomagnetite to establish two-oxide disequilibrium as a geospeedometer. Our data constrain oxide-oxide re-equilibration timescales at Mt. Unzen to months, consistent with estimates from zoned, single crystals of magnetite [3,4]. Future experiments will examine the effect of oxygen fugacity on diffusivity in ilmenite solid solutions. References:[1] Van Orman & Crispin (2010) RiMG 72, 757-825.[2] Bacon & Hirschmann (1988) Am. Min. 73, 57-61.[3] Nakamura (1995) Geology 23, 807-810.[4] Venezky & Rutherford (1999) J. Volc. Geo. Res. 89, 213-230.

Mass Dependency of Isotope Fractionation of Gases Under Thermal Gradient and Its Possible Implications for Planetary Atmosphere Escaping Process

NASA Technical Reports Server (NTRS)

Sun, Tao; Niles, Paul; Bao, Huiming; Socki, Richard

2014-01-01

Physical processes that unmix elements/isotopes of gas molecules involve phase changes, diffusion (chemical or thermal), effusion and gravitational settling. Some of those play significant roles for the evolution of chemical and isotopic compositions of gases in planetary bodies which lead to better understanding of surface paleoclimatic conditions, e.g. gas bubbles in Antarctic ice, and planetary evolution, e.g. the solar-wind erosion induced gas escaping from exosphere on terrestrial planets.. A mass dependent relationship is always expected for the kinetic isotope fractionations during these simple physical processes, according to the kinetic theory of gases by Chapman, Enskog and others [3-5]. For O-bearing (O16, -O17, -O18) molecules the alpha O-17/ alpha O-18 is expected at 0.5 to 0.515, and for S-bearing (S32,-S33. -S34, -S36) molecules, the alpha S-33/ alpha S-34 is expected at 0.5 to 0.508, where alpha is the isotope fractionation factor associated with unmixing processes. Thus, one isotope pair is generally proxied to yield all the information for the physical history of the gases. However, we recently] reported the violation of mass law for isotope fractionation among isotope pairs of multiple isotope system during gas diffusion or convection under thermal gradient (Thermal Gradient Induced Non-Mass Dependent effect, TGI-NMD). The mechanism(s) that is responsible to such striking observation remains unanswered. In our past studies, we investigated polyatomic molecules, O2 and SF6, and we suggested that nuclear spin effect could be responsible to the observed NMD effect in a way of changing diffusion coefficients of certain molecules, owing to the fact of negligible delta S-36 anomaly for SF6.. On the other hand, our results also showed that for both diffusion and convection under thermal gradient, this NMD effect is increased by lower gas pressure, bigger temperature gradient and lower average temperature, which indicate that the nuclear spin effect may not be the significant contributor as the energies involved in the hyperfine effect are much smaller than those with molecular collisions, especially under convective conditions.

Mechanisms of high-temperature, solid-state flow in minerals and ceramics and their bearing on the creep behavior of the mantle

USGS Publications Warehouse

Kirby, S.H.; Raleigh, C.B.

1973-01-01

The problem of applying laboratory silicate-flow data to the mantle, where conditions can be vastly different, is approached through a critical review of high-temperature flow mechanisms in ceramics and their relation to empirical flow laws. The intimate association of solid-state diffusion and high-temperature creep in pure metals is found to apply to ceramics as well. It is shown that in ceramics of moderate grain size, compared on the basis of self-diffusivity and elastic modulus, normalized creep rates compare remarkably well. This comparison is paralleled by the near universal occurrence of similar creep-induced structures, and it is thought that the derived empirical flow laws can be associated with dislocation creep. Creep data in fine-grained ceramics, on the other hand, are found to compare poorly with theories involving the stress-directed diffusion of point defects and have not been successfully correlated by self-diffusion rates. We conclude that these fine-grained materials creep primarily by a quasi-viscous grain-boundary sliding mechanism which is unlikely to predominate in the earth's deep interior. Creep predictions for the mantle reveal that under most conditions the empirical dislocation creep behavior predominates over the mechanisms involving the stress-directed diffusion of point defects. The probable role of polymorphic transformations in the transition zone is also discussed. ?? 1973.

A polymeric colchicinoid prodrug with reduced toxicity and improved efficacy for vascular disruption in cancer therapy

PubMed Central

Crielaard, Bart J; van der Wal, Steffen; Lammers, Twan; Le, Huong Thu; Hennink, Wim E; Schiffelers, Raymond M; Storm, Gert; Fens, Marcel HAM

2011-01-01

Colchicinoids are very potent tubulin-binding compounds, which interfere with microtubule formation, giving them strong cytotoxic properties, such as cell mitosis inhibition and induction of microcytoskeleton depolymerization. While this makes them promising vascular disrupting agents (VDAs) in cancer therapy, their dose-limiting toxicity has prevented any clinical application for this purpose. Therefore, colchicinoids are considered attractive lead molecules for the development of novel vascular disrupting nanomedicine. In a previous study, a polymeric colchicinoid prodrug that showed favorable hydrolysis characteristics at physiological conditions was developed. In the current study, this polymeric colchicinoid prodrug was evaluated in vitro and in vivo for its toxicity and vascular disrupting potential. Cell viability studies with human umbilical vein endothelial cells, as an in vitro measure for colchicine activity, reflected the degradation kinetics of the prodrug accordingly. Upon intravenous treatment, in vivo, of B16F10 melanoma-bearing mice with colchicine or with the polymeric colchicinoid prodrug, apparent vascular disruption and consequent tumor necrosis was observed for the prodrug but not for free colchicine at an equivalent dose. Moreover, a five-times-higher dose of the prodrug was well tolerated, indicating reduced toxicity. These findings demonstrate that the polymeric colchicinoid prodrug has a substantially improved efficacy/toxicity ratio compared with that of colchicine, making it a promising VDA for cancer therapy. PMID:22114500

Isotherm and kinetic studies on adsorption of oil sands process-affected water organic compounds using granular activated carbon.

PubMed

Islam, Md Shahinoor; McPhedran, Kerry N; Messele, Selamawit A; Liu, Yang; Gamal El-Din, Mohamed

2018-07-01

The production of oil from oil sands in northern Alberta has led to the generation of large volumes of oil sands process-affected water (OSPW) that was reported to be toxic to aquatic and other living organisms. The toxicity of OSPW has been attributed to the complex nature of OSPW matrix including the inorganic and organic compounds primarily naphthenic acids (NAs: C n H 2n+Z O x ). In the present study, granular activated carbon (GAC) adsorption was investigated for its potential use to treat raw and ozonated OSPW. The results indicated that NA species removal increased with carbon number (n) for a fixed Z number; however, the NA species removal decreased with Z number for a fixed carbon number. The maximum adsorption capacities obtained from Langmuir adsorption isotherm based on acid-extractable fraction (AEF) and NAs were 98.5 mg and 60.9 mg AEF/g GAC and 60 mg and 37 mg NA/g GAC for raw and ozonated OSPW, respectively. It was found that the Freundlich isotherm model best fits the AEF and NA equilibrium data (r 2  ≥ 0.88). The adsorption kinetics showed that the pseudo-second order and intraparticle diffusion models were both appropriate in modeling the adsorption kinetics of AEF and NAs to GAC (r 2  ≥ 0.97). Although pore diffusion was the rate limiting step, film diffusion was still significant for assessing the rate of diffusion of NAs. This study could be helpful to model, design and optimize the adsorption treatment technologies of OSPW and to assess the performance of other adsorbents. Copyright © 2018 Elsevier Ltd. All rights reserved.

Deliverability and efficacy of R-CHOP chemotherapy in very elderly patients with diffuse large B-cell lymphoma: an Australian retrospective analysis.

PubMed

Millar, A; Ellis, M; Mollee, P; Cochrane, T; Fletcher, J; Caudron, A; Webster, B; Trotman, J

2015-11-01

Elderly patients with diffuse large B-cell lymphoma (DLBCL) have an inferior prognosis, due in part to advanced age and pre-existing comorbidities, with reduced tolerability and deliverability of standard R-CHOP chemotherapy. To examine the deliverability, toxicity and efficacy of R-CHOP and the prevalence of the germinal and non-germinal phenotype DLBCL in an elderly Australian cohort. This retrospective analysis included patients ≥75 years diagnosed with DLBCL. Comprehensive chemotherapy and toxicity data were collected for patients treated with R-CHOP. Baseline demographics and chemotherapy characteristics were compared with progression-free (PFS) and overall survival (OS). Immunohistochemical staining identified the prevalence of the non-germinal centre (non-GCB) phenotype. Of the 111 patients, 92 (83%) commenced R-CHOP with 26/92 (28%) receiving ≤4 cycles. Median average relative dose (ARD) was 0.80 (0.07-1.17). Median average relative dose intensity (ARDI) was 0.89 (0.33-1.18). Serious adverse events occurred in 77% of patients with ≥Gd3 adverse events in 74%. Overall response rate was 85%. Two-year PFS was 63% and OS 74%. ARD and performance status ≥2 were significant prognostic factors for PFS and OS but not ARDI. Non-GCB-phenotype was identified in 44/72 (61%) of patients with immunohistochemical data. Despite high response rates and respectable survival estimates, the absence of standard therapy in 17% of patients, and dose reductions and serious toxicity of R-CHOP in this Australian cohort highlights the need for the development of less toxic yet efficacious treatments for very elderly patients with DLBCL. The high prevalence of the non-GCB phenotype highlights the potential value of targeted biological therapy for this demographic. © 2015 Royal Australasian College of Physicians.

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

PubMed

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

2015-10-20

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

Anti-Candida activity and brine shrimp toxicity assay of Ganoderma boninense.

PubMed

Daruliza, K M A; Fernandez, L; Jegathambigai, R; Sasidharan, S

2012-01-01

Ganoderma (G.) boninense is a white rot fungus, which can be found in the palm oil tree. Several studies have shown that G. boninense has antimicrobial and antagonistic properties. However, there is limited information reported on antifungal properties especially on Candida (C) albicans. Hence, this study was conducted to determine the anti-Candida activity of G. boninense against C albicans. Crude methanolic extracts of G. boninense was obtained by maceration method with 70% methanol. Anti-Candida test was carried out using disc diffusion assay, broth dilution method, time killing profile and brine shrimp toxicity assay. Anti-Candida activity indicated that the mean zone of inhibition was 12.5 +/- 0.6 mm. The MIC value for C. albicans found to be 3.125 mg/ml. The result from time-killing profile showed that the growth of C albicans was inhibited hence decreases its exponential phase. For brine shrimp toxicity assay, the LC50 value was 3.59 mg/ml which proved that the extract of G. boninense is not toxic.

Vibration characteristics of the HPOTP (High-Pressure Oxygen Turbopump) of the SSME (Space Shuttle Main Engine)

NASA Technical Reports Server (NTRS)

Childs, D. W.; Moyer, D. S.

1984-01-01

Attention is given to rotor dynamic problems that have been encountered and eliminated in the course of Space Shuttle Main Engine (SSME) development, as well as continuing, subsynchronous problems which are being encountered in the development of a 109-percent power level engine. The basic model for the SSME's High Pressure Oxygen Turbopump (HPOTP) encompasses a structural dynamic model for the rotor and housing, and component models for the liquid and gas seals, turbine clearance excitation forces, and impeller diffuser forces. Linear model results are used to examine the synchronous response and stability characteristics of the HPOTP, with attention to bearing load and stability problems associated with the second critical speed. Differences between linear and nonlinear model results are discussed and explained in terms of simple models. Simulation results indicate that while synchronous bearing loads can be reduced, subsynchronous motion is not eliminated by seal modifications.

Hydrogeological constraints on riparian buffers for reduction of diffuse pollution: examples from the Bear Creek watershed in Iowa, USA.

PubMed

Simpkins, W W; Wineland, T R; Andress, R J; Johnston, D A; Caron, G C; Isenhart, T M; Schultz, R C

2002-01-01

Riparian Management Systems (RiMS) have been proposed to minimize the impacts of agricultural production and improve water quality in Iowa in the Midwestern USA. As part of RiMS, multispecies riparian buffers have been shown to decrease nutrient, pesticide, and sediment concentrations in runoff from adjacent crop fields. However, their effect on nutrients and pesticides moving in groundwater beneath buffers has been discussed only in limited and idealized hydrogeologic settings. Studies in the Bear Creek watershed of central Iowa show the variability inherent in hydrogeologic systems at the watershed scale, some of which may be favorable or unfavorable to future implementation of buffers. Buffers may be optimized by choosing hydrogeologic systems where a shallow groundwater flow system channels water directly through the riparian buffer at velocities that allow for processes such as denitrification to occur.

Thermally induced cation redistribution in Fe-bearing oxy-dravite and potential geothermometric implications

NASA Astrophysics Data System (ADS)

Bosi, Ferdinando; Skogby, Henrik; Hålenius, Ulf

2016-05-01

Iron-bearing oxy-dravite was thermally treated in air and hydrogen atmosphere at 800 °C to study potential changes in Fe, Mg and Al ordering over the octahedrally coordinated Y and Z sites and to explore possible applications to intersite geothermometry based on tourmaline. Overall, the experimental data (structural refinement, Mössbauer, infrared and optical absorption spectroscopy) show that heating Fe-bearing tourmalines results in disordering of Fe over Y and Z balanced by ordering of Mg at Y, whereas Al does not change appreciably. The Fe disorder depends on temperature, but less on redox conditions. The degree of Fe3+-Fe2+ reduction is limited despite strongly reducing conditions, indicating that the f O2 conditions do not exclusively control the Fe oxidation state at the present experimental conditions. Untreated and treated samples have similar short- and long-range crystal structures, which are explained by stable Al-extended clusters around the O1 and O3 sites. In contrast to the stable Al clusters that preclude any temperature-dependent Mg-Al order-disorder, there occurs Mg diffusion linked to temperature-dependent exchange with Fe. Ferric iron mainly resides around O2- at O1 rather than (OH)-, but its intersite disorder induced by thermal treatment indicates that Fe redistribution is the driving force for Mg-Fe exchange and that its diffusion rates are significant at these temperatures. With increasing temperature, Fe progressively disorders over Y and Z, whereas Mg orders at Y according to the order-disorder reaction: YFe + ZMg → ZFe + YMg. The presented findings are important for interpretation of the post-crystallization history of both tourmaline and tourmaline host rocks and imply that successful tourmaline geothermometers may be developed by thermal calibration of the Mg-Fe order-disorder reaction, whereas any thermometers based on Mg-Al disorder will be insensitive and involve large uncertainties.

Effects of Molybdenum Addition on Hydrogen Desorption of TiC Precipitation-Hardened Steel

NASA Astrophysics Data System (ADS)

Song, Eun Ju; Baek, Seung-Wook; Nahm, Seung Hoon; Suh, Dong-Woo

2018-05-01

The hydrogen-trap states in TiC and MoC that have coherent interfaces with ferrite were investigated using first-principles calculation. The trapping sites of TiC were the interfaces and interstitial sites of ferrite. On the other hand, the trapping sites of MoC were ferrite interstitial sites; the interface had a negative binding energy with H. Thermal desorption analysis confirms that the amounts of diffusible hydrogen were significantly reduced by addition of Mo in Ti-bearing steel.

Random Walk of Single Gold Nanoparticles in Zebrafish Embryos Leading to Stochastic Toxic Effects on Embryonic Developments

PubMed Central

Browning, Lauren M.; Lee, Kerry J.; Huang, Tao; Nallathamby, Prakash D.; Lowman, Jill E.; Xu, Xiao-Hong Nancy

2010-01-01

We have synthesized and characterized stable (non-aggregation, non-photobleaching and non-blinking), nearly monodisperse and highly-purified Au nanoparticles, and used them to probe transport of cleavage-stage zebrafish embryos and to study their effects on embryonic development in real time. We found that single Au nanoparticles (11.6 ± 0.9 nm in diameter) passively diffused into chorionic space of the embryos via their chorionic-pore-canals and continued their random-walk through chorionic space and into inner mass of embryos. Diffusion coefficients of single nanoparticles vary dramatically (2.8×10-11 to 1.3×10-8 cm2/s) as nanoparticles diffuse through various parts of embryos, suggesting highly diverse transport barriers and viscosity gradients of embryos. The amount of Au nanoparticles accumulated in embryos increase with its concentration. Interestingly, their effects on embryonic development are not proportionally related to the concentration. Majority of embryos (74% on average) incubated chronically with 0.025-1.2 nM Au nanoparticles for 120 h developed to normal zebrafish, with some (24%) being dead and few (2%) deformed. We developed a new approach to image and characterize individual Au nanoparticles embedded in tissues using histology sample preparation methods and LSRP spectra of single nanoparticles. We found that Au nanoparticles in various parts of normally developed and deformed zebrafish, suggesting that random-walk of nanoparticles in embryos during their development might have led to stochastic effects on embryonic development. These results show that Au nanoparticles are much more biocompatible (less toxic) to the embryos than Ag nanoparticles that we reported previously, suggesting that they are better suited as biocompatible probes for imaging embryos in vivo. The results provide powerful evidences that biocompatibility and toxicity of nanoparticles highly depend on their chemical properties, and the embryos can serve as effective in-vivo assays to screen their biocompatibility. PMID:20644873

Assessment of the geoavailability of trace elements from selected zinc minerals

USGS Publications Warehouse

Driscoll, Rhonda L.; Hageman, Phillip L.; Benzel, William M.; Diehl, Sharon F.; Morman, Suzette; Choate, LaDonna M.; Lowers, Heather

2014-01-01

This assessment focused on five zinc-bearing minerals. The minerals were subjected to a number of analyses including quantitative X-ray diffraction, optical microscopy, leaching tests, and bioaccessibility and toxicity studies. Like a previous comprehensive assessment of five copper-bearing minerals, the purpose of this assessment was to obtain structural and chemical information and to characterize the reactivity of each mineral to various simulated environmental and biological conditions. As in the copper minerals study, analyses were conducted consistent with widely accepted methods. Unless otherwise noted, analytical methods used for this study were identical to those described in the investigation of copper-bearing minerals. Two sphalerite specimens were included in the zinc-minerals set. One sphalerite was recovered from a mine in Balmat, New York; the second came from a mine in Creede, Colorado. The location and conditions of origin are significant because, as analyses confirmed, the two sphalerite specimens are quite different. For example, data acquired from a simulated gastric fluid (SGF) study indicate that the hydrothermally formed Creede sphalerite contains orders of magnitude higher arsenic, cadmium, manganese, and lead than the much older metamorphic Balmat sphalerite. The SGF and other experimental results contained in this report suggest that crystallizing conditions such as temperature, pressure, fluidization, or alteration processes significantly affect mineral properties—properties that, in turn, influence reactivity, solubility, and toxicity. The three remaining minerals analyzed for this report—smithsonite, hemimorphite, and hydrozincite—are all secondary minerals or alteration products of zinc-ore deposits. In addition, all share physical characteristics such as tenacity, density, streak, and cleavage. Similarities end there. The chemical composition, unit-cell parameters, acid-neutralizing potential, and other observable and quantifiable properties indicate very different minerals. Only one of each of these minerals was studied. Had this assessment included multiples of these minerals, geochemical and mineralogical distinctions would have emerged, similar to the results for the two sphalerite specimens.

Microwave-Assisted Condensation Reactions of Acetophenone Derivatives and Activated Methylene Compounds with Aldehydes Catalyzed by Boric Acid under Solvent-Free Conditions.

PubMed

Brun, Elodie; Safer, Abdelmounaim; Carreaux, François; Bourahla, Khadidja; L'helgoua'ch, Jean-Martial; Bazureau, Jean-Pierre; Villalgordo, Jose Manuel

2015-06-23

We here disclosed a new protocol for the condensation of acetophenone derivatives and active methylene compounds with aldehydes in the presence of boric acid under microwave conditions. Implementation of the reaction is simple, healthy and environmentally friendly owing to the use of a non-toxic catalyst coupled to a solvent-free procedure. A large variety of known or novel compounds have thus been prepared, including with substrates bearing acid or base-sensitive functional groups.

A new distraction arthroplasty device using magnetic force; a cadaveric study.

PubMed

Kamei, Goki; Ochi, Mitsuo; Okuhara, Atsushi; Fujimiya, Mineko; Deie, Masataka; Adachi, Nobuo; Nakamae, Atsuo; Nakasa, Tomoyuki; Ohkawa, Shingo; Takazawa, Kobun; Eguchi, Akio; Katou, Tomohiro; Takada, Tsuyoshi; Usman, Muhammad Andry

2013-04-01

It is difficult for an articular cartilage injury to repair spontaneously. There are many procedures for treating cartilage injury, however there is no standard procedure for middle-aged patients who have diffuse knee osteoarthritis, especially of the lateral compartment. Therefore, Ochi developed a new distraction device that uses magnetic power to enlarge a joint space and promote cartilage regeneration with microfracture. The purpose of this study is to evaluate this new distraction arthroplasty system by using the cadaveric knee. This study used ten knees from six cadavers that were embalmed by Thiel's methods. The medial and lateral joint space was measured by AP radiographic view before and after distraction, and after weight-bearing to evaluate the joint distraction. The contact pressure of the medial and lateral compartments at the knee extension position by using a prescale film system was measured before and after weight-bearing with a 15 or 30-kg weight-bearing load to evaluate the effectiveness of this device. The lateral joint space significantly increased from the pre-distraction to the post-distraction; however, it did not change significantly between post-distraction and post-weight-bearing. With a 15 or 30-kg weight-bearing load, the contact pressure of the lateral compartment significantly decreased from the pre-distraction to the post-distraction. The most important advantage of this device is that it maintains a continuous distraction tension and enables almost the full range of motion of the knee. We believe that joint distraction by using magnetic force can be a promising option for cartilage injury in middle-aged patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

Hematological toxicity and therapeutic efficacy of lomustine in 20 tumor-bearing cats: critical assessment of a practical dosing regimen.

PubMed

Fan, Timothy M; Kitchell, Barbara E; Dhaliwal, Ravinder S; Jones, Pamela D; Hintermeister, John G; Paria, Biman C

2002-01-01

Twenty cats with spontaneously arising tumors received oral lomustine at a dose range of 32 to 59 mg/m2 every 21 days. Due to biohazard concerns associated with lomustine capsule reformulation, a standardized 10-mg capsule dosage was used for all cats regardless of body weight. Severe hematological toxicity was infrequent, with the incidence of either grade III or IV neutropenia and thrombocytopenia being 4.1% and 1.0%, respectively. Cats receiving higher cumulative doses of lomustine trended toward a greater likelihood for progressive neutropenia (P=0.07). Two cats with lymphoma, two cats with fibrosarcoma, and one cat with multiple myeloma achieved a measurable partial response to lomustine therapy. Cats treated with higher dosages of lomustine trended toward statistically significant higher response rates (P=0.07).

Near-infrared mediated tumor destruction by photothermal effect of PANI-Np in vivo

NASA Astrophysics Data System (ADS)

Ibarra, L. E.; Yslas, E. I.; Molina, M. A.; Rivarola, C. R.; Romanini, S.; Barbero, C. A.; Rivarola, V. A.; Bertuzzi, M. L.

2013-06-01

Photothermal therapy is a therapy in which photon energy is converted into heat to kill cancer. The purpose of this study is to evaluate the in vivo efficacy of photothermal therapy, toxicity and hepatic and renal function of polyaniline nanoparticles (PANI-Np) in a tumor-bearing mice model. The in vivo efficacy of nanoparticles, following NIR light exposure, was assessed by examining tumor growth over time compared to the untreated control. Signs of drug toxicity and the histopathology and morphology of tumor and tissues, after intratumoral injection treatment, were examined or monitored. Excellent photothermal therapy efficacy is achieved upon intratumoral injection of PANI-Np followed by near-infrared light exposure. These results suggest that PANI-Np could be considered as an effective photothermal agent and pave the way to future cancer therapeutics.

Regorafenib inhibits tumor progression through suppression of ERK/NF-κB activation in hepatocellular carcinoma bearing mice.

PubMed

Weng, Mao-Chi; Wang, Mei-Hui; Tsai, Jai-Jen; Kuo, Yu-Cheng; Liu, Yu-Chang; Hsu, Fei-Ting; Wang, Hsin-Ell

2018-06-29

Regorafenib has been demonstrated in our previous study to trigger apoptosis through suppression of extracellular signal-regulated kinase (ERK)/nuclear factor-κB (NF-κB) activation in hepatocellular carcinoma (HCC) SK-Hep1 cells in vitro However, the effect of regorafenib on NF-κB-modulated tumor progression in HCC in vivo is ambiguous. The aim of the present study is to investigate the effect of regorafenib on NF-κB-modulated tumor progression in HCC bearing mouse model. pGL4.50 luciferase reporter vector transfected SK-Hep1 (SK-Hep1/ luc2 ) and Hep3B 2.1-7 tumor bearing mice were established and used for the present study. Mice were treated with vehicle or regorafenib (20 mg/kg/day by gavage) for 14 days. Effects of regorafenib on tumor growth and protein expression together with toxicity of regorafenib were evaluated with digital caliper and bioluminescence imaging (BLI), ex vivo Western blotting immunohistochemistry (IHC) staining, and measurement of body weight and pathological examination of liver tissue, respectively, in SK-Hep1/ luc2 and Hep3B 2.1-7 tumor bearing mice. The results indicated regorafenib significantly reduced tumor growth and expression of phosphorylated ERK, NF-κB p65 (Ser536), phosphorylated AKT, and tumor progression-associated proteins. In addition, we found regorafenib induced both extrinsic and intrinsic apoptotic pathways. Body weight and liver morphology were not affected by regorafenib treatment. Our findings present the mechanism of tumor progression inhibition by regorafenib is linked to suppression of ERK/NF-κB signaling in SK-Hep1/ luc2 and Hep3B 2.1-7 tumor bearing mice. © 2018 The Author(s).

Isolating isomers of perfluorocarboxylates in polar bears (Ursus maritimus) from two geographical locations.

PubMed

De Silva, Amila O; Mabury, Scott A

2004-12-15

The source of involatile, anthropogenic perfluorocarboxylate anions (PFCAs) in biota from remote regions is of heightened interest due to the persistence, toxicity, and bioaccumulation of these materials. Large-scale production of fluorinated compounds is carried out primarily by one of two methods: electrochemical fluorination (ECF) and telomerization. Products of the two processes may be distinguished based on constitutional isomer pattern as ECF products are characteristically comprised of a variety of constitutional isomers. The objective of this research was to develop a method for identifying the constitutional isomer profile of PFCAs in environmental samples and to apply the method to polar bear livers from two different locations. Resolution of constitutional isomers of derivatized PFCAs (8-13 carbons) was accomplished via GC-MS. Seven isomers of an authentic ECF perfluorooctanoate (PFOA) standard were separated. The linear isomer comprised 78% of this standard. Isomer profiles of PFCAs in liver samples of 15 polar bears (Ursus maritimus) from the Canadian Arctic and eastern Greenland were determined by GC-MS. The PFOA isomer pattern in Greenland polar bear samples showed a variety of branched isomers while only the linear PFOA isomer was determined in Canadian samples. Samples of both locations had primarily (>99%) linear isomers of perfluorononanoate and perfluorotridecanoate. Branched isomers of perfluorodecanoate, perfluoroundecanoate, and perfluorododecanoate were determined in the polar bear samples. Unlike the PFOA isomer signature, only a single branched isomer peak on the chromatograms was observed for these longer chain PFCAs. The presence of branched isomers suggests some contribution from ECF sources. However, in comparison to the amount of branched isomers in the ECF PFOA standard, such minor percentages of branched PFCAs may suggest additional input from an exclusively linear isomer source.

Social Influence and the Autism Epidemic1

PubMed Central

Liu, Ka-Yuet; King, Marissa; Bearman, Peter S.

2010-01-01

Despite a plethora of studies, we do not know why autism incidence has increased rapidly over the past two decades. Using California data, this study shows that children living very close to a child previously diagnosed with autism are more likely to be diagnosed with autism. An underlying social influence mechanism involving information diffusion drives this result, contributing to 16% of the increase in prevalence over 2000–2005. We eliminate competing explanations (i.e., residential sorting, environmental toxicants, and viral transmission) through seven tests and show that information diffusion simultaneously contributed to the increased prevalence, spatial clustering, and decreasing age of diagnosis. PMID:20503647

Effect of Iron and Carbonation of the Diffusion of Iodine and Rhenium in Waste Encasement Concrete and Soil Fill Material under Hydraulically Unsaturated Conditions

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

Wellman, Dawn M.; Parker, Kent E.; Powers, Laura

2008-07-31

Assessing long-term performance of Category 3 cement wasteforms and accurate prediction for radionuclide encasement requires knowledge of the radionuclide-cement interactions and mechanisms of retention (i.e. sorption or precipitation). A set of sediment-concrete half-cell diffusion experiments was conducted under unsaturated conditions (4% and 7% by weight moisture content) using carbonated and non-carbonated concrete-soil half-cells. Results indicate the behavior of rhenium and iodine release was comparable within a given half-cell test. Diffusivity in soil is a function of moisture content; a 3% increase in moisture content affords a one to two order of magnitude increase in diffusivity. Release of iodine and rheniummore » was 1 to 3 orders of magnitude less from non-carbonated, relative to carbonated, concrete monoliths. Inclusion of iron in non-carbonate monoliths resulted in the lowest concrete diffusivity values for both iodine and rhenium. This suggests that in the presence of iron, iodine and rhenium are converted to reduced species, which are less soluble and better retained within the concrete monolith. The release of iodine and rhenium was greatest from iron-bearing, carbonated concrete monoliths, suggesting carbonation negates the effect of iron on the retention of iodine and rhenium within concrete monoliths. This is likely due to enhanced formation of microcracks in the presence of iron, which provide preferential paths for contaminant migration. Although the release of iodine and rhenium were greatest from carbonated concrete monoliths containing iron, the migration of iodine and rhenium within a given half-cell is dependent on the moisture content, soil diffusivity, and diffusing species.« less

Simultaneous determination of thermal conductivity, thermal diffusivity and specific heat in sI methane hydrate

USGS Publications Warehouse

Waite, W.F.; Stern, L.A.; Kirby, S.H.; Winters, W.J.; Mason, D.H.

2007-01-01

Thermal conductivity, thermal diffusivity and specific heat of sI methane hydrate were measured as functions of temperature and pressure using a needle probe technique. The temperature dependence was measured between −20°C and 17°C at 31.5 MPa. The pressure dependence was measured between 31.5 and 102 MPa at 14.4°C. Only weak temperature and pressure dependencies were observed. Methane hydrate thermal conductivity differs from that of water by less than 10 per cent, too little to provide a sensitive measure of hydrate content in water-saturated systems. Thermal diffusivity of methane hydrate is more than twice that of water, however, and its specific heat is about half that of water. Thus, when drilling into or through hydrate-rich sediment, heat from the borehole can raise the formation temperature more than 20 per cent faster than if the formation's pore space contains only water. Thermal properties of methane hydrate should be considered in safety and economic assessments of hydrate-bearing sediment.

An Investigation into the Effects of Process Conditions on the Tribological Performance of Pack Carburized Titanium with Limited Oxygen Diffusion

NASA Astrophysics Data System (ADS)

Bailey, R.; Sun, Y.

2018-04-01

In the present study, a new pack carburization technique for titanium has been investigated. The aim of this treatment is to produce a titanium carbide/oxycarbide layer atop of an extended oxygen diffusion zone [α-Ti(O)]. The effects of treatment temperature and pack composition have been investigated in order to determine the optimal conditions required to grant the best tribological response. The resulting structural features were investigated with particular interest in the carbon and oxygen concentrations across the samples cross section. The optimization showed that a temperature of 925 °C with a pack composition of 1 part carbon to 1 part energizer produced surface capable of withstanding a contact pressure of ≈ 1.5 GPa for 1 h. The process resulted in TiC surface structure which offers enhanced hardness (2100 HV) and generates a low friction coefficient (μ ≈ 0.2) when in dry sliding contact with an alumina (Al2O3) ball. The process also produced an extended oxygen diffusion zone that helps to improve the load bearing capacity of the substrate.

An Experimental and Finite Element Protocol to Investigate the Transport of Neutral and Charged Solutes across Articular Cartilage.

PubMed

Arbabi, Vahid; Pouran, Behdad; Zadpoor, Amir A; Weinans, Harrie

2017-04-23

Osteoarthritis (OA) is a debilitating disease that is associated with degeneration of articular cartilage and subchondral bone. Degeneration of articular cartilage impairs its load-bearing function substantially as it experiences tremendous chemical degradation, i.e. proteoglycan loss and collagen fibril disruption. One promising way to investigate chemical damage mechanisms during OA is to expose the cartilage specimens to an external solute and monitor the diffusion of the molecules. The degree of cartilage damage (i.e. concentration and configuration of essential macromolecules) is associated with collisional energy loss of external solutes while moving across articular cartilage creates different diffusion characteristics compared to healthy cartilage. In this study, we introduce a protocol, which consists of several steps and is based on previously developed experimental micro-Computed Tomography (micro-CT) and finite element modeling. The transport of charged and uncharged iodinated molecules is first recorded using micro-CT, which is followed by applying biphasic-solute and multiphasic finite element models to obtain diffusion coefficients and fixed charge densities across cartilage zones.

In vivo tomographic imaging of lung colonization of tumour in mouse with simultaneous fluorescence and X-ray CT.

PubMed

Zhang, Bin; Gao, Fuping; Wang, Mengjiao; Cao, Xu; Liu, Fei; Wang, Xin; Luo, Jianwen; Wang, Guangzhi; Bai, Jing

2014-01-01

Non-invasive in vivo imaging of diffuse and wide-spread colonization within the lungs, rather than distinct solid primary tumors, is still a challenging work. In this work, a lung colonization mouse model bearing A549 human lung tumor was simultaneously scanned by a dual-modality fluorescence molecular tomography (FMT) and X-ray computed tomography (CT) system in vivo. A two steps method which incorporates CT structural information into the FMT reconstruction procedure is employed to provide concurrent anatomical and functional information. By using the target-specific fluorescence agent, the fluorescence tomographic results show elevated fluorescence intensity deep within the lungs which is colonized with diffuse and wide-spread tumors. The results were confirmed with ex vivo fluorescence reflectance imaging and histological examination of the lung tissues. With FMT reconstruction combined with the CT information, the dual-modality FMT/micro-CT system is expected to offer sensitive and noninvasive imaging of diffuse tumor colonization within the lungs in vivo. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Phlegmonous gastritis associated with group A streptococcal toxic shock syndrome.

PubMed

Morimoto, Masaya; Tamura, Shinobu; Hayakawa, Takahiro; Yamanishi, Hirofumi; Nakamoto, Chiaki; Nakamoto, Hiromichi; Ikebe, Tadayoshi; Nakano, Yoshio; Fujimoto, Tokuzo

2014-01-01

Phlegmonous gastritis (PG) is a rare, acute, severe infectious disease of the gastric wall that is often fatal due to Streptococcus spp. A 77-year-old man with diabetes and a gastric ulcer was urgently admitted due to prolonged nausea and vomiting. Computed tomography revealed widespread diffuse thickening of the gastric wall, and PG was suspected. The patient expired less than 9 hours after admission despite intensive treatments. Later, an analysis of the blood and gastric juice revealed group A streptococcus (GAS) and virulence factors associated with toxic shock syndrome (TSS). We herein diagnosed a patient with an extremely aggressive course of PG caused by GAS TSS.

Methane Hydrate Formation in Thick Sand Reservoirs: Long-range Gas Transport or Short-range Methane Diffusion?

NASA Astrophysics Data System (ADS)

You, K.; Flemings, P. B.

2016-12-01

We developed two 2-D numerical models to simulate hydrate formation by long range methane gas transport and short-range methane diffusion. We interpret that methane hydrates in thick sands are most likely formed by long range gas transport where methane gas is transported upward into the hydrate stability zone (HSZ) under buoyancy and locally forms hydrate to its stability limit. In short-range methane diffusion, methane is generated locally by biodegradation of organic matter in mud and diffused into bounding sands where it forms hydrate. We could not simulate enough methane transport by diffusion to account for its observed concentration in thick sands. In our models, we include the capillary effect on dissolved methane solubility and on the hydrate phase boundary, sedimentation and different compaction in sand and mud, fracture generation as well as the fully coupled multiphase flow and multicomponent transport. We apply our models to a 12 meter-thick hydrate-bearing sand layer at Walker Ridge 313, Northern Gulf of Mexico. With the long-range gas transport, hydrate saturation is greater than 90% and salinity is increased from seawater to about 8 wt.% through the entire sand. With short-range diffusion, hydrate saturation is more than 90% at the sand base and is less than 10% in the overlying section; salinity is close to seawater when sand is deposited to 800 meter below seafloor by short-range methane diffusion. With short-range diffusion, the amount of hydrate formed is much less than that interpreted from the well log data. Two transient gas layers separated by a hydrate layer are formed from short-range diffusion caused by capillary effect. This could be interpreted as a double bottom simulating reflector. This study provides further insights into different hydrate formation mechanisms, and could serve as a base to confirm the hydrate formation mechanism in fields.

O-GlcNAc modification blocks the aggregation and toxicity of the protein α-synuclein associated with Parkinson's disease

NASA Astrophysics Data System (ADS)

Marotta, Nicholas P.; Lin, Yu Hsuan; Lewis, Yuka E.; Ambroso, Mark R.; Zaro, Balyn W.; Roth, Maxwell T.; Arnold, Don B.; Langen, Ralf; Pratt, Matthew R.

2015-11-01

Several aggregation-prone proteins associated with neurodegenerative diseases can be modified by O-linked N-acetyl-glucosamine (O-GlcNAc) in vivo. One of these proteins, α-synuclein, is a toxic aggregating protein associated with synucleinopathies, including Parkinson's disease. However, the effect of O-GlcNAcylation on α-synuclein is not clear. Here, we use synthetic protein chemistry to generate both unmodified α-synuclein and α-synuclein bearing a site-specific O-GlcNAc modification at the physiologically relevant threonine residue 72. We show that this single modification has a notable and substoichiometric inhibitory effect on α-synuclein aggregation, while not affecting the membrane binding or bending properties of α-synuclein. O-GlcNAcylation is also shown to affect the phosphorylation of α-synuclein in vitro and block the toxicity of α-synuclein that was exogenously added to cells in culture. These results suggest that increasing O-GlcNAcylation may slow the progression of synucleinopathies and further support a general function for O-GlcNAc in preventing protein aggregation.

Modular degradable dendrimers enable small RNAs to extend survival in an aggressive liver cancer model

PubMed Central

Zhou, Kejin; Nguyen, Liem H.; Miller, Jason B.; Yan, Yunfeng; Kos, Petra; Xiong, Hu; Li, Lin; Hao, Jing; Minnig, Jonathan T.; Siegwart, Daniel J.

2016-01-01

RNA-based cancer therapies are hindered by the lack of delivery vehicles that avoid cancer-induced organ dysfunction, which exacerbates carrier toxicity. We address this issue by reporting modular degradable dendrimers that achieve the required combination of high potency to tumors and low hepatotoxicity to provide a pronounced survival benefit in an aggressive genetic cancer model. More than 1,500 dendrimers were synthesized using sequential, orthogonal reactions where ester degradability was systematically integrated with chemically diversified cores, peripheries, and generations. A lead dendrimer, 5A2-SC8, provided a broad therapeutic window: identified as potent [EC50 < 0.02 mg/kg siRNA against FVII (siFVII)] in dose–response experiments, and well tolerated in separate toxicity studies in chronically ill mice bearing MYC-driven tumors (>75 mg/kg dendrimer repeated dosing). Delivery of let-7g microRNA (miRNA) mimic inhibited tumor growth and dramatically extended survival. Efficacy stemmed from a combination of a small RNA with the dendrimer’s own negligible toxicity, therefore illuminating an underappreciated complication in treating cancer with RNA-based drugs. PMID:26729861

Cabazitaxel-loaded human serum albumin nanoparticles as a therapeutic agent against prostate cancer

PubMed Central

Qu, Na; Lee, Robert J; Sun, Yating; Cai, Guangsheng; Wang, Junyang; Wang, Mengqiao; Lu, Jiahui; Meng, Qingfan; Teng, Lirong; Wang, Di; Teng, Lesheng

2016-01-01

Cabazitaxel-loaded human serum albumin nanoparticles (Cbz-NPs) were synthesized to overcome vehicle-related toxicity of current clinical formulation of the drug based on Tween-80 (Cbz-Tween). A salting-out method was used for NP synthesis that avoids the use of chlorinated organic solvent and is simpler compared to the methods based on emulsion-solvent evaporation. Cbz-NPs had a narrow particle size distribution, suitable drug loading content (4.9%), and superior blood biocompatibility based on in vitro hemolysis assay. Blood circulation, tumor uptake, and antitumor activity of Cbz-NPs were assessed in prostatic cancer xenograft-bearing nude mice. Cbz-NPs exhibited prolonged blood circulation and greater accumulation of Cbz in tumors along with reduced toxicity compared to Cbz-Tween. Moreover, hematoxylin and eosin histopathological staining of organs revealed consistent results. The levels of blood urea nitrogen and serum creatinine in drug-treated mice showed that Cbz-NPs were less toxic than Cbz-Tween to the kidneys. In conclusion, Cbz-NPs provide a promising therapeutic for prostate cancer. PMID:27555767

Building a Better Quaternary Ammonium Compound (QAC): Branched Tetracationic Antiseptic Amphiphiles.

PubMed

Forman, Megan E; Jennings, Megan C; Wuest, William M; Minbiole, Kevin P C

2016-07-05

Bacteria contaminate surfaces in a wide variety of environments, causing severe problems across a number of industries. In a continuation of our campaign to develop novel antibacterial quaternary ammonium compounds (QACs) as useful antiseptics, we have identified a starting material bearing four tertiary amines, enabling the rapid synthesis of several tris- and tetracationic QACs. Herein we report the synthesis and biological activity of a series of 24 multiQACs deemed the "superT" family, and an investigation of the role of cationic charge in antimicrobial and anti-biofilm activity, as well as toxicity. This class represents the most potent series of QACs reported to date against methicillin-resistant Staphylococcus aureus (MRSA), with minimum inhibitory concentrations (MICs) and minimum biofilm eradication concentrations (MBECs) as low as 0.25 and 25 μm, respectively. Based on the significant cell-surface-charge differences between bacterial and eukaryotic cells, in certain cases we observed excellent efficacy-to-toxicity profiles, exceeding a 100-fold differential. This work further elucidates the chemical underpinnings of disinfectant efficacy versus toxicity based on cationic charge. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Relationship between toxicities and clinical benefits of newly approved tyrosine kinase inhibitors in thyroid cancer: A meta-analysis of literature.

PubMed

Ye, Xiaobing; Zhu, Yiping; Cai, Juan

2015-10-01

The aim of this meta-analysis was to analyze the relationship of toxicities and clinical benefits of newly approved lenvatinib and sorafenib to thyroid cancer (TC) in patients. Three major medical databases, PubMed, EMBASE, and ISI web of science were systematically searched to identify all studies on lenvatinib and sorafenib in TC. A meta-analysis was performed to clarify the toxicities and clinical benefits of newly Food and Drug Administration (FDA) approved lenvatinib and sorafenib to thyroid cancer. Ten studies (n = 749) were included which evaluated the toxicities and clinical benefits of newly FDA approved lenvatinib and sorafenib to thyroid cancer. 537 (71.7%) of the 749 patients bearing TC (radioiodine-refractory, differentiated thyroid cancer) clinical benefits from lenvatinib or sorafenib, and serious adverse events occurred in 430 (57.4%) of the 749 patients ([risk ratio (RR) = 1.27, 95% confidence interval (CI) = (1.05-1.53), P = 0.01]). While 31 (4.1%) of the 749 patients died due to various reasons, that mainly accounts for severe bleeding events and cardiac arrest. The clinical benefit is obvious compared to deaths ([RR = 17.06, 95% CI = (12.08-24.11), P < 0.001]). Subgroup analyses were then conducted according to cancer type (radioiodine-refractory thyroid cancer [RR-TC] and TC). We found that in treating RR-TC, the clinical benefits are close to toxicities. While in treating TC, the clinical benefits are better than toxicities. And we found that sorafenib and lenvatinib might be proper to deal with TC (benefits rate 79.7%) compared to RR-TC (benefits rate 69.5%), taking consider of toxicities. Lenvatinib and sorafenib are useful in the treatment of TC. Although, their toxicities remain high (57.4%) in the patients, the death rate is controlled (4.1%). Take consider of toxicities, lenvatinib, and sorafenib are more useful for TC compared to RR-TC.

Comparisons of hybrid radiosity-diffusion model and diffusion equation for bioluminescence tomography in cavity cancer detection

NASA Astrophysics Data System (ADS)

Chen, Xueli; Yang, Defu; Qu, Xiaochao; Hu, Hao; Liang, Jimin; Gao, Xinbo; Tian, Jie

2012-06-01

Bioluminescence tomography (BLT) has been successfully applied to the detection and therapeutic evaluation of solid cancers. However, the existing BLT reconstruction algorithms are not accurate enough for cavity cancer detection because of neglecting the void problem. Motivated by the ability of the hybrid radiosity-diffusion model (HRDM) in describing the light propagation in cavity organs, an HRDM-based BLT reconstruction algorithm was provided for the specific problem of cavity cancer detection. HRDM has been applied to optical tomography but is limited to simple and regular geometries because of the complexity in coupling the boundary between the scattering and void region. In the provided algorithm, HRDM was first applied to three-dimensional complicated and irregular geometries and then employed as the forward light transport model to describe the bioluminescent light propagation in tissues. Combining HRDM with the sparse reconstruction strategy, the cavity cancer cells labeled with bioluminescent probes can be more accurately reconstructed. Compared with the diffusion equation based reconstruction algorithm, the essentiality and superiority of the HRDM-based algorithm were demonstrated with simulation, phantom and animal studies. An in vivo gastric cancer-bearing nude mouse experiment was conducted, whose results revealed the ability and feasibility of the HRDM-based algorithm in the biomedical application of gastric cancer detection.

Comparisons of hybrid radiosity-diffusion model and diffusion equation for bioluminescence tomography in cavity cancer detection.

PubMed

Chen, Xueli; Yang, Defu; Qu, Xiaochao; Hu, Hao; Liang, Jimin; Gao, Xinbo; Tian, Jie

2012-06-01

Bioluminescence tomography (BLT) has been successfully applied to the detection and therapeutic evaluation of solid cancers. However, the existing BLT reconstruction algorithms are not accurate enough for cavity cancer detection because of neglecting the void problem. Motivated by the ability of the hybrid radiosity-diffusion model (HRDM) in describing the light propagation in cavity organs, an HRDM-based BLT reconstruction algorithm was provided for the specific problem of cavity cancer detection. HRDM has been applied to optical tomography but is limited to simple and regular geometries because of the complexity in coupling the boundary between the scattering and void region. In the provided algorithm, HRDM was first applied to three-dimensional complicated and irregular geometries and then employed as the forward light transport model to describe the bioluminescent light propagation in tissues. Combining HRDM with the sparse reconstruction strategy, the cavity cancer cells labeled with bioluminescent probes can be more accurately reconstructed. Compared with the diffusion equation based reconstruction algorithm, the essentiality and superiority of the HRDM-based algorithm were demonstrated with simulation, phantom and animal studies. An in vivo gastric cancer-bearing nude mouse experiment was conducted, whose results revealed the ability and feasibility of the HRDM-based algorithm in the biomedical application of gastric cancer detection.

Titanite chronology, thermometry, and speedometry of ultrahigh-temperature (UHT) calc-silicates from south Madagascar: U-Pb dates, Zr temperatures, and lengthscales of trace-element diffusion

NASA Astrophysics Data System (ADS)

Holder, R. M.; Hacker, B. R.

2017-12-01

Calc-silicate rocks are often overlooked as sources of pressure-temperature-time data in granulite-UHT metamorphic terranes due to the strong dependence of calc-silicate mineral assemblages on complex fluid compositions and a lack of thermodynamic data on common high-temperature calc-silicate minerals such as scapolite. In the Ediacaran-Cambrian UHT rocks of southern Madagascar, clinopyroxene-scapolite-feldspar-quartz-zircon-titanite calc-silicate rocks are wide-spread. U-Pb dates of 540-520 Ma from unaltered portions of titanite correspond to cooling of the rocks through upper-amphibolite facies and indicate UHT metamorphism occurred before 540 Ma. Zr concentrations in these domains preserve growth temperatures of 900-950 °C, consistent with peak temperatures calculated by pseudosection modeling of nearby osumilite-bearing gneisses. Younger U-Pb dates (510-490 Ma) correspond to fluid-mediated Pb loss from titanite grains, which occurred below their diffusive Pb-closure temperature, along fractures. The extent of fluid alteration is seen clearly in back-scattered electron images and Zr-, Al-, Fe-, Ce-, and Nb-concentration maps. Laser-ablation depth profiling of idioblastic titanite grains shows preserved Pb diffusion profiles at grain rims, but there is no evidence for Zr diffusion, indicating that it was effectively immobile even at UHT.

Multilayer Spheroids To Quantify Drug Uptake and Diffusion in 3D

PubMed Central

2015-01-01

There is a need for new quantitative in vitro models of drug uptake and diffusion to help assess drug toxicity/efficacy as well as new more predictive models for drug discovery. We report a three-dimensional (3D) multilayer spheroid model and a new algorithm to quantitatively study uptake and inward diffusion of fluorescent calcein via gap junction intercellular communication (GJIC). When incubated with calcein-AM, a substrate of the efflux transporter P-glycoprotein (Pgp), spheroids from a variety of cell types accumulated calcein over time. Accumulation decreased in spheroids overexpressing Pgp (HEK-MDR) and was increased in the presence of Pgp inhibitors (verapamil, loperamide, cyclosporin A). Inward diffusion of calcein was negligible in spheroids that lacked GJIC (OVCAR-3, SK-OV-3) and was reduced in the presence of an inhibitor of GJIC (carbenoxolone). In addition to inhibiting Pgp, verapamil and loperamide, but not cyclosporin A, inhibited inward diffusion of calcein, suggesting that they also inhibit GJIC. The dose response curves of verapamil’s inhibition of Pgp and GJIC were similar (IC50: 8 μM). The method is amenable to many different cell types and may serve as a quantitative 3D model that more accurately replicates in vivo barriers to drug uptake and diffusion. PMID:24641346

Impacts of aircraft deicer and anti-icer runoff on receiving waters from Dallas/Fort Worth International Airport, Texas, U.S.A.

PubMed

Corsi, Steven R; Harwell, Glenn R; Geis, Steven W; Bergman, Daniel

2006-11-01

From October 2002 to April 2004, data were collected from Dallas/Fort Worth (DFW) International Airport (TX, U.S.A.) outfalls and receiving waters (Trigg Lake and Big Bear Creek) to document the magnitude and potential effects of aircraft deicer and anti-icer fluid (ADAF) runoff on water quality. Glycol concentrations at outfalls ranged from less than 18 to 23,800 mg/L, whereas concentrations in Big Bear Creek were less because of dilution, dispersion, and degradation, ranging from less than 18 to 230 mg/L. Annual loading results indicate that 10 and 35% of what was applied to aircraft was discharged to Big Bear Creek in 2003 and 2004, respectively. Glycol that entered Trigg Lake was diluted and degraded before reaching the lake outlet. Dissolved oxygen (DO) concentrations at airport outfalls sometimes were low (<2.0 mg/L) but typical of what was measured in an urban reference stream. In comparison, the DO concentration at Trigg Lake monitoring sites was consistently greater than 5.5 mg/L during the monitoring period, probably because of the installation of aerators in the lake by DFW personnel. The DO concentration in Big Bear Creek was very similar at sites upstream and downstream of airport influence (>5.0 mg/L). Results of toxicity tests indicate that effects on Ceriodaphnia dubia, Pimephales promelas, and Selanastrum capricornutum are influenced by type IV ADAF (anti-icer), not just type I ADAF (deicer) as is more commonly assumed.

Comparative hepatic microsomal biotransformation of selected PBDEs, including decabromodiphenyl ether, and decabromodiphenyl ethane flame retardants in Arctic marine-feeding mammals.

PubMed

McKinney, Melissa A; Dietz, Rune; Sonne, Christian; De Guise, Sylvain; Skirnisson, Karl; Karlsson, Karl; Steingrímsson, Egill; Letcher, Robert J

2011-07-01

The present study assessed and compared the oxidative and reductive biotransformation of brominated flame retardants, including established polybrominated diphenyl ethers (PBDEs) and emerging decabromodiphenyl ethane (DBDPE) using an in vitro system based on liver microsomes from various arctic marine-feeding mammals: polar bear (Ursus maritimus), beluga whale (Delphinapterus leucas), and ringed seal (Pusa hispida), and in laboratory rat as a mammalian model species. Greater depletion of fully brominated BDE209 (14-25% of 30 pmol) and DBDPE (44-74% of 90 pmol) occurred in individuals from all species relative to depletion of lower brominated PBDEs (BDEs 99, 100, and 154; 0-3% of 30 pmol). No evidence of simply debrominated metabolites was observed. Investigation of phenolic metabolites in rat and polar bear revealed formation of two phenolic, likely multiply debrominated, DBDPE metabolites in polar bear and one phenolic BDE154 metabolite in polar bear and rat microsomes. For BDE209 and DBDPE, observed metabolite concentrations were low to nondetectable, despite substantial parent depletion. These findings suggested possible underestimation of the ecosystem burden of total-BDE209, as well as its transformation products, and a need for research to identify and characterize the persistence and toxicity of major BDE209 metabolites. Similar cause for concern may exist regarding DBDPE, given similarities of physicochemical and environmental behavior to BDE209, current evidence of biotransformation, and increasing use of DBDPE as a replacement for BDE209. Copyright © 2011 SETAC.

Trace and macro elements in the femoral bone as indicators of long-term environmental exposure to toxic metals in European brown bear (Ursus arctos) from Croatia.

PubMed

Lazarus, Maja; Orct, Tatjana; Reljić, Slaven; Sedak, Marija; Bilandžić, Nina; Jurasović, Jasna; Huber, Đuro

2018-05-21

We explored the long-term accumulation of aluminium, strontium, cadmium and lead in the compact and trabecular bone of the femoral epiphysis, metaphysis and diaphysis in 41 brown bears (Ursus arctos) from Croatia. Also, we assessed their influence on macro and trace elements (sodium, magnesium, phosphorus, potassium, calcium, manganese, iron, cobalt, copper, zinc and barium) in bears' bone. There were no sex differences in element levels in general, while age was associated with bone length and levels of all elements, except for cadmium. Elements had different levels depending on the part of the bone sampled. More pronounced differences were observed between the compact and trabecular regions, with higher levels of majority of elements found in compact bone. Moderate to high associations (Spearman coefficient, r S  = 0.59-0.97) were confirmed between calcium and potassium, magnesium, phosphorus, manganese, cobalt, zinc, strontium and lead. Lead levels in the bone were below those known to cause adverse health effects, but in 4 of 41 animals they exceeded baseline levels for domestic animals. The femoral bone of the brown bear reflected the accumulative nature of lead and strontium well, as it did the impairment of bone-forming essential element levels associated with these two elements. However, the distribution pattern of elements along the bone was not uniform, so additional care should be taken when choosing on the part of the bone sampled.

Improving anticancer activity and reducing systemic toxicity of doxorubicin by self-assembled polymeric micelles

NASA Astrophysics Data System (ADS)

Gou, MaLing; Shi, HuaShan; Guo, Gang; Men, Ke; Zhang, Juan; Zheng, Lan; Li, ZhiYong; Luo, Feng; Qian, ZhiYong; Zhao, Xia; Wei, YuQuan

2011-03-01

In an attempt to improve anticancer activity and reduce systemic toxicity of doxorubicin (Dox), we encapsulated Dox in monomethoxy poly(ethylene glycol)-poly(ɛ-caprolactone) (MPEG-PCL) micelles by a novel self-assembly procedure without using surfactants, organic solvents or vigorous stirring. These Dox encapsulated MPEG-PCL (Dox/MPEG-PCL) micelles with drug loading of 4.2% were monodisperse and ~ 20 nm in diameter. The Dox can be released from the Dox/MPEG-PCL micelles; the Dox-release at pH 5.5 was faster than that at pH 7.0. Encapsulation of Dox in MPEG-PCL micelles enhanced the cellular uptake and cytotoxicity of Dox on the C-26 colon carcinoma cell in vitro, and slowed the extravasation of Dox in the transgenic zebrafish model. Compared to free Dox, Dox/MPEG-PCL micelles were more effective in inhibiting tumor growth in the subcutaneous C-26 colon carcinoma and Lewis lung carcinoma models, and prolonging survival of mice bearing these tumors. Dox/MPEG-PCL micelles also induced lower systemic toxicity than free Dox. In conclusion, incorporation of Dox in MPEG-PCL micelles enhanced the anticancer activity and decreased the systemic toxicity of Dox; these Dox/MPEG-PCL micelles are an interesting formulation of Dox and may have potential clinical applications in cancer therapy.

Determination of biodegradability kinetics of RCRA compounds using respirometry for structure-activity relationships

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

Tabak, H.H.; Desai, S.; Govind, R.

1990-01-01

Electrolytic respirometry is attaining prominence in biodegradation studies and is becoming one of the more suitable experimental methods for measuring the biodegradability and the kinetics of biodegradation of toxic organic compounds by the sewage, sludge, and soil microbiota and for determining substrate inhibitory effects to microorganisms in wastewater treatment systems. The purpose of the study was to obtain information on biological treatability of the benzene, phenol, phthalate, ketone organics and of the Superfund CERCLA organics bearing wastes in wastewater treatment systems which will support the development of an EPA technical guidance document on the discharge of the above organics tomore » POTWs. The paper discusses the experimental design and procedural steps for the respirometric biodegradation and toxicity testing approach for individual organics or specific industrial wastes at different concentration levels in a mineral salts medium. A developed multi-level protocol is presented for determination of the biodegradability, microbial acclimation to toxic substrates and first order kinetic parameters of biodegradation for estimation of the Monod kinetic parameter of toxic organic compounds, in order to correlate the extent and rate of biodegradation with a predictive model based on chemical properties and molecular structure of these compounds. Respirometric biodegradation/inhibition and biokinetic data are provided for representative RCRA alkyl benzene and ketone organics.« less

Influence of cell shape, inhomogeneities and diffusion barriers in cell polarization models

NASA Astrophysics Data System (ADS)

Giese, Wolfgang; Eigel, Martin; Westerheide, Sebastian; Engwer, Christian; Klipp, Edda

2015-12-01

In silico experiments bear the potential for further understanding of biological transport processes by allowing a systematic modification of any spatial property and providing immediate simulation results. Cell polarization and spatial reorganization of membrane proteins are fundamental for cell division, chemotaxis and morphogenesis. We chose the yeast Saccharomyces cerevisiae as an exemplary model system which entails the shuttling of small Rho GTPases such as Cdc42 and Rho, between an active membrane-bound form and an inactive cytosolic form. We used partial differential equations to describe the membrane-cytosol shuttling of proteins. In this study, a consistent extension of a class of 1D reaction-diffusion systems into higher space dimensions is suggested. The membrane is modeled as a thin layer to allow for lateral diffusion and the cytosol is modeled as an enclosed volume. Two well-known polarization mechanisms were considered. One shows the classical Turing-instability patterns, the other exhibits wave-pinning dynamics. For both models, we investigated how cell shape and diffusion barriers like septin structures or bud scars influence the formation of signaling molecule clusters and subsequent polarization. An extensive set of in silico experiments with different modeling hypotheses illustrated the dependence of cell polarization models on local membrane curvature, cell size and inhomogeneities on the membrane and in the cytosol. In particular, the results of our computer simulations suggested that for both mechanisms, local diffusion barriers on the membrane facilitate Rho GTPase aggregation, while diffusion barriers in the cytosol and cell protrusions limit spontaneous molecule aggregations of active Rho GTPase locally.

Multiplexed measurement of protein diffusion in Caenorhabditis elegans embryos with SPIM-FCS

NASA Astrophysics Data System (ADS)

Struntz, Philipp; Weiss, Matthias

2016-02-01

Quantifying the diffusion behavior of proteins in different environments, e.g. on cellular membranes, is a key step in uncovering the vital action of protein networks in living organisms. While several established techniques for local diffusion measurements exist, the life sciences are currently in need of a multiplexed, i.e. spatially parallelized, data acquisition that allows for obtaining diffusion maps with high spatiotemporal resolution. Following this demand, the combination of camera-based single-plane illumination microscopy (SPIM) and fluorescence correlation spectroscopy (FCS) has recently emerged as a promising approach. So far, SPIM-FCS has mainly been used to assess the diffusion of soluble particles and proteins in vitro and in culture cells, but due to a particularly low photobleaching and -toxicity the method is also well applicable to developmental organisms. Here, we have probed the performance of SPIM-FCS on an established developmental model organism, the small nematode Caenorhabditis elegans. In particular, we have quantified the diffusion of the peripheral membrane protein PLC1δ 1 in the embryo’s cytoplasm and on the plasma membrane. As a result, we were able to derive diffusion maps of PLC1δ 1 in both compartments in multiple individuals, showing the spatially varying diffusion coefficients across the embryo. Our data also report on the dissociation kinetics of PLC1δ 1 from the plasma membrane, hence underlining that SPIM-FCS can be used to explore key features of peripheral membrane proteins in fragile developmental model organisms.

TEMPORAL AND SPATIAL VARIATION IN SOLAR RADIATION AND PHOTO-ENHANCED TOXICITY RISKS OF SPILLED OIL IN PRINCE WILLIAM SOUND, ALASKA

EPA Science Inventory

Solar irradiance (W/m2) and downwelling diffuse attenuation coefficients (Kd; m-1) were determined in several locations in Prince William Sound, Alaska, USA, between April 2003 and December 2005 to assess temporal and spatial variation in solar radiation and the risks of photoenh...

Report on the Biological Monitoring Program at Paducah Gaseous Diffusion Plant, January--December 1995

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

Kszos, L.A.

1996-04-01

The BMP for PGDP consists of three major tasks: (1) effluent and ambient toxicity monitoring, (2) bioaccumulation studies, and (3) ecological surveys of stream communities (benthic macroinvertebrates, fish). This report focuses on ESD activities occurring from Jan. 1995 to Dec. 1995, although activities conducted outside this period are included as appropriate.

SCALE-UP OF RAPID SMALL-SCALE ADSORPTION TESTS TO FIELD-SCALE ADSORBERS: THEORETICAL BASIS AND EXPERIMENTAL RESULTS FOR A CONSTANT DIFFUSIVITY

EPA Science Inventory

Granular activated carbon (GAC) is an effective treatment technique for the removal of some toxic organics from drinking water or wastewater, however, it can be a relatively expensive process, especially if it is designed improperly. A rapid method for the design of large-scale f...

Effect of deep injection on field-scale emissions of 1,3-dichloropropene and chloropicrin from bare soil

USDA-ARS?s Scientific Manuscript database

Fumigating soil is important for the production of many high-value vegetable, fruit, and tree crops, but fumigants are toxic and highly volatile which can lead to significant atmospheric emissions. A field experiment was conducted to measure emissions and subsurface diffusion of a mixture of 1,3-di...

Electroencephalography and phenytoin toxicity in mentally retarded epileptic patients.

PubMed Central

Iivanainen, M; Viukari, M; Seppäläinen, A M; Helle, E P

1978-01-01

There were significantly more diffuse and focal electroencephalographic abnormalities in 127 mentally retarded epileptic patients treated with phenytoin than in 68 epileptics without phenytoin. Phenytoin intoxication made the difference still more pronounced. Monitoring drug levels and electroencephalograms appears to be the method of choice for ensuring safe and effective medication in intractable epilepsy. PMID:632825

The Analgesic Acetaminophen and the Antipsychotic Clozapine Can Each Redox-Cycle with Melanin.

PubMed

Temoçin, Zülfikar; Kim, Eunkyoung; Li, Jinyang; Panzella, Lucia; Alfieri, Maria Laura; Napolitano, Alessandra; Kelly, Deanna L; Bentley, William E; Payne, Gregory F

2017-12-20

Melanins are ubiquitous but their complexity and insolubility has hindered characterization of their structures and functions. We are developing electrochemical reverse engineering methodologies that focus on properties and especially on redox properties. Previous studies have shown that melanins (i) are redox-active and can rapidly and repeatedly exchange electrons with diffusible oxidants and reductants, and (ii) have redox potentials in midregion of the physiological range. These properties suggest the functional activities of melanins will depend on their redox context. The brain has a complex redox context with steep local gradients in O 2 that can promote redox-cycling between melanin and diffusible redox-active chemical species. Here, we performed in vitro reverse engineering studies and report that melanins can redox-cycle with two common redox-active drugs. Experimentally, we used two melanin models: a convenient natural melanin derived from cuttlefish (Sepia melanin) and a synthetic cysteinyldopamine-dopamine core-shell model of neuromelanin. One drug, acetaminophen (APAP), has been used clinically for over a century, and recent studies suggest that low doses of APAP can protect the brain from oxidative-stress-induced toxicity and neurodegeneration, while higher doses can have toxic effects in the brain. The second drug, clozapine (CLZ), is a second generation antipsychotic with polypharmacological activities that remain incompletely understood. These in vitro observations suggest that the redox activities of drugs may be relevant to their modes-of-action, and that melanins may interact with drugs in ways that affect their activities, metabolism, and toxicities.

Evaluation of the ability of arsenic species to traverse cell membranes by simple diffusion using octanol-water and liposome-water partition coefficients.

PubMed

Chávez-Capilla, Teresa; Maher, William; Kelly, Tamsin; Foster, Simon

2016-11-01

Arsenic metabolism in living organisms is dependent on the ability of different arsenic species to traverse biological membranes. Simple diffusion provides an alternative influx and efflux route to mediated transport mechanisms that can increase the amount of arsenic available for metabolism in cells. Using octanol-water and liposome-water partition coefficients, the ability of arsenous acid, arsenate, methylarsonate, dimethylarsinate, thio-methylarsonate, thio-dimethylarsinic acid, arsenotriglutathione and monomethylarsonic diglutathione to diffuse through the lipid bilayer of cell membranes was investigated. Molecular modelling of arsenic species was used to explain the results. All arsenic species with the exception of arsenate, methylarsonate and thio-methylarsonate were able to diffuse through the lipid bilayer of liposomes, with liposome-water partition coefficients between 0.04 and 0.13. Trivalent arsenic species and thio-pentavalent arsenic species showed higher partition coefficients, suggesting that they can easily traverse cell membranes by passive simple diffusion. Given the higher toxicity of these species compared to oxo-pentavalent arsenic species, this study provides evidence supporting the risk associated with human exposure to trivalent and thio-arsenic species. Copyright © 2016. Published by Elsevier B.V.

Chloroquine diphosphate bearing dextran nanoparticles augmented drug delivery and overwhelmed drug resistance in Plasmodium falciparum parasites.

PubMed

Kashyap, Aman; Kaur, Rupinder; Baldi, Ashish; Jain, Upendra Kumar; Chandra, Ramesh; Madan, Jitender

2018-07-15

Chloroquine diphosphate (CHQ) is primarily used for the treatment of Plasmodium falciparum malaria at the dose of 500mg orally or 10mg/kg parenterally. However, point mutations in Plasmodiumfalciparum chloroquine resistance transporter (PfCRT) protein and Plasmodium falciparum multidrug resistance protein 1 (Pfmdr1) localized in digestive vacuole membrane, are responsible for CHQ resistance. Therefore, in present investigation, dextran nanoparticles bearing chloroquine diphosphate (CHQ-DEX-NPs) were formulated by solvent diffusion method of size below 70nm with zeta-potential of -20.1±3.2mV. FT-IR, DSC and PXRD techniques confirmed the successful loading of drug in nanomatrix system with amorphous attributes. In vitro drug release analysis indicated the Higuchi pattern with diffusion controlled drug release. The IC 50 of CHQ-DEX-NPs in sensitive (3D7) and resistant (RKL9) Plasmodium falciparum strains was estimated to be 0.031-μg/ml and 0.13-μg/ml significantly lower than 0.059-μg/ml and 0.36-μg/ml of CHQ. The augmented therapeutic efficacy of CHQ-DEX-NPs may be credited to deposition of tailored nanoparticles in food vacuoles of malaria parasites owing to the affinity of parasite towards DEX that consequently lower the drug resistance and improved the therapeutic index. In conclusion, CHQ-DEX-NPs must be evaluated under a set of stringent in vivo parameters to establish its therapeutic efficacy in preclinical model. Copyright © 2018 Elsevier B.V. All rights reserved.

The Comparison of Biodistribution, Efficacy and Toxicity of Two PEGylated Liposomal Doxorubicin Formulations in Mice Bearing C-26 Colon Carcinoma: a Preclinical Study.

PubMed

Razavi-Azarkhiavi, K; Jafarian, A H; Abnous, K; Razavi, B M; Shirani, K; Zeinali, M; Jaafari, M R; Karimi, G

2016-06-01

Over the past several years, the considerable attention has been progressively given to liposomal formulations of anthracyclines. SinaDoxosome(®) (Exir Nano Sina Company, Iran) is a pegylated liposomal doxorubicin (DOX) which approved by Food and Drug Administration of IRAN for treatment of some types of cancer. The aim of this study was to compare the biodistribution, efficacy, cardiotoxicity and hepatotoxicity of SinaDoxosome(®) with Caelyx(®) in mice bearing C-26 colon carcinoma. Mice tumor size evaluation during the experimental period (28 days) showed comparable therapeutic efficacy of nano-formulations. The biodistribution studies showed no significant difference in DOX tissue concentration between Caelyx(®) and SinaDoxosome(®). DOX induced-ECG changes were not detected in nano-formulations. No significant alteration was found in biochemical indexes of myocardial injury in mice exposed to nano-formulations in comparison with control mice. The tissue oxidative parameters such as lipid peroxidation, glutathione, catalase and superoxide dismutase was significantly changed as the results of free DOX treatment. However, the oxidative status of Caelyx(®) and SinaDoxosome(®) treated animals did not showed any changes. The experiment also revealed that apoptotic pathway was not activated in the heart of mice exposed to nano-formulations. Although this investigation showed that Caelyx(®) and SinaDoxosome(®) are similar in terms of biodistribution, efficacy and toxicity, appropriate clinical evaluations in patients should be considered. © Georg Thieme Verlag KG Stuttgart · New York.

Geogenic organic contaminants in the low-rank coal-bearing Carrizo-Wilcox aquifer of East Texas, USA

NASA Astrophysics Data System (ADS)

Chakraborty, Jayeeta; Varonka, Matthew; Orem, William; Finkelman, Robert B.; Manton, William

2017-06-01

The organic composition of groundwater along the Carrizo-Wilcox aquifer in East Texas (USA), sampled from rural wells in May and September 2015, was examined as part of a larger study of the potential health and environmental effects of organic compounds derived from low-rank coals. The quality of water from the low-rank coal-bearing Carrizo-Wilcox aquifer is a potential environmental concern and no detailed studies of the organic compounds in this aquifer have been published. Organic compounds identified in the water samples included: aliphatics and their fatty acid derivatives, phenols, biphenyls, N-, O-, and S-containing heterocyclic compounds, polycyclic aromatic hydrocarbons (PAHs), aromatic amines, and phthalates. Many of the identified organic compounds (aliphatics, phenols, heterocyclic compounds, PAHs) are geogenic and originated from groundwater leaching of young and unmetamorphosed low-rank coals. Estimated concentrations of individual compounds ranged from about 3.9 to 0.01 μg/L. In many rural areas in East Texas, coal strata provide aquifers for drinking water wells. Organic compounds observed in groundwater are likely to be present in drinking water supplied from wells that penetrate the coal. Some of the organic compounds identified in the water samples are potentially toxic to humans, but at the estimated levels in these samples, the compounds are unlikely to cause acute health problems. The human health effects of low-level chronic exposure to coal-derived organic compounds in drinking water in East Texas are currently unknown, and continuing studies will evaluate possible toxicity.

Direct estimation of diffuse gaseous emissions from coal fires: current methods and future directions

USGS Publications Warehouse

Engle, Mark A.; Olea, Ricardo A.; O'Keefe, Jennifer M. K.; Hower, James C.; Geboy, Nicholas J.

2013-01-01

Coal fires occur in nature spontaneously, contribute to increases in greenhouse gases, and emit atmospheric toxicants. Increasing interest in quantifying coal fire emissions has resulted in the adaptation and development of specialized approaches and adoption of numerical modeling techniques. Overview of these methods for direct estimation of diffuse gas emissions from coal fires is presented in this paper. Here we take advantage of stochastic Gaussian simulation to interpolate CO2 fluxes measured using a dynamic closed chamber at the Ruth Mullins coal fire in Perry County, Kentucky. This approach allows for preparing a map of diffuse gas emissions, one of the two primary ways that gases emanate from coal fires, and establishing the reliability of the study both locally and for the entire fire. Future research directions include continuous and automated sampling to improve quantification of gaseous coal fire emissions.

Hg diffusion in books of XVIII and XIX centuries by synchrotron microprobe

NASA Astrophysics Data System (ADS)

Pessanha, S.; Carvalho, M. L.; Manso, M.; Guilherme, A.; Marques, A. F.; Perez, C. A.

2009-08-01

The pigment vermilion (HgS) was used to color the fore edge, tail and head of books. Dissemination and quantification of Hg present in the ink used to color books from XVIII and XIX centuries are reported. Mercury is a very toxic element for the human body, therefore it is extremely important to know whether Hg tends to disseminate throughout the paper or stays confined to the borders of the books with less danger for readers. Synchrotron X-ray microprobe was used to evaluate Hg dissemination from the border to the centre of the paper sheet. The diffusion pattern of Hg was compared with the results obtained by a portable X-ray fluorescence spectrometer and mean quantitative calculations were obtained by a stationary X-ray fluorescence system with triaxial geometry. The results showed high concentrations of Hg in the external regions, but no diffusion was observed for the inner parts of the paper.

Acute and chronic neuropsychological consequences of mercury vapor poisoning in two early adolescents.

PubMed

Yeates, K O; Mortensen, M E

1994-04-01

Mercury is an extremely toxic heavy metal that can devastate the central nervous system. The neuropsychological consequences of mercury vapor intoxication have been studied primarily in adults. We present two adolescent half-siblings, ages 13 and 15, who were unintentionally exposed to concentrated mercury vapor for 3 months. Both children participated in neuropsychological evaluations shortly after being diagnosed with mercury toxicity, and again 1 year later. Results from the initial assessments documented functional deficits consistent with diffuse encephalopathy. Upon follow-up, neuropsychological functioning had improved, but deficits remained in visuoperceptual and constructional skills, nonverbal memory, and conceptual abstraction. The deficits persisted despite removal from exposure, return of urinary and blood mercury to acceptable levels, and resolution of neuropsychiatric symptoms. The deficits were similar to, but more severe than, those found in adults suffering from mercury vapor intoxication. The results suggest that the developing brain may be especially vulnerable to mercury vapor toxicity.

Preclinical Biosafety Evaluation of Genetically Modified Human Adipose Tissue-Derived Mesenchymal Stem Cells for Clinical Applications to Brainstem Glioma.

PubMed

Choi, Seung Ah; Yun, Jun-Won; Joo, Kyeung Min; Lee, Ji Yeoun; Kwak, Pil Ae; Lee, Young Eun; You, Ji-Ran; Kwon, Euna; Kim, Woo Ho; Wang, Kyu-Chang; Phi, Ji Hoon; Kang, Byeong-Cheol; Kim, Seung-Ki

2016-06-15

Stem-cell based gene therapy is a promising novel therapeutic approach for inoperable invasive tumors, including brainstem glioma. Previously, we demonstrated the therapeutic potential of human adipose tissue-derived mesenchymal stem cells (hAT-MSC) genetically engineered to express a secreted form of tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) against brainstem glioma. However, safety concerns should be comprehensively investigated before clinical applications of hAT-MSC.sTRAIL. At first, we injected stereotactically low (1.2 × 10(5) cells/18 μL), medium (2.4 × 10(5)/18 μL), or high dose (3.6 × 10(5)/18 μL) of hAT-MSC.sTRAIL into the brainstems of immunodeficient mice reflecting the plan of the future clinical trial. Local toxicity, systemic toxicity, secondary tumor formation, and biodistribution of hAT-MSC.sTRAIL were investigated. Next, presence of hAT-MSC.sTRAIL was confirmed in the brain and major organs at 4, 9, and 14 weeks in brainstem glioma-bearing mice. In the 15-week subchronic toxicity test, no serious adverse events in terms of body weight, food consumption, clinical symptom, urinalysis, hematology, clinical chemistry, organ weight, and histopathology were observed. In the 26-week tumorigenicity test, hAT-MSC.sTRAIL made no detectable tumors, whereas positive control U-87 MG cells made huge tumors in the brainstem. No remaining hAT-MSC.sTRAIL was observed in any organs examined, including the brainstem at 15 or 26 weeks. In brainstem glioma-bearing mice, injected hAT-MSC.sTRAIL was observed, but gradually decreased over time in the brain. The mRNA of human specific GAPDH and TRAIL was not detected in all major organs. These results indicate that the hAT-MSC.sTRAIL could be applicable to the future clinical trials in terms of biosafety.

Cd Mobility in Anoxic Fe-Mineral-Rich Environments - Potential Use of Fe(III)-Reducing Bacteria in Soil Remediation

NASA Astrophysics Data System (ADS)

Muehe, E. M.; Adaktylou, I. J.; Obst, M.; Schröder, C.; Behrens, S.; Hitchcock, A. P.; Tylsizczak, T.; Michel, F. M.; Krämer, U.; Kappler, A.

2014-12-01

Agricultural soils are increasingly burdened with heavy metals such as Cd from industrial sources and impure fertilizers. Metal contaminants enter the food chain via plant uptake from soil and negatively affect human and environmental health. New remediation approaches are needed to lower soil metal contents. To apply these remediation techniques successfully, it is necessary to understand how soil microbes and minerals interact with toxic metals. Here we show that microbial Fe(III) reduction initially mobilizes Cd before its immobilization under anoxic conditions. To study how microbial Fe(III) reduction influences Cd mobility, we isolated a new Cd-tolerant, Fe(III)-reducing Geobacter sp. from a heavily Cd-contaminated soil. In lab experiments, this Geobacter strain first mobilized Cd from Cd-loaded Fe(III) hydroxides followed by precipitation of Cd-bearing mineral phases. Using Mössbauer spectroscopy and scanning electron microscopy, the original and newly formed Cd-containing Fe(II) and Fe(III) mineral phases, including Cd-Fe-carbonates, Fe-phosphates and Fe-(oxyhydr)oxides, were identified and characterized. Using energy-dispersive X-ray spectroscopy and synchrotron-based scanning transmission X-ray microscopy, Cd was mapped in the Fe(II) mineral aggregates formed during microbial Fe(III) reduction. Microbial Fe(III) reduction mobilizes Cd prior to its precipitation in Cd-bearing mineral phases. The mobilized Cd could be taken up by phytoremediating plants, resulting in a net removal of Cd from contaminated sites. Alternatively, Cd precipitation could reduce Cd bioavailability in the environment, causing less toxic effects to crops and soil microbiota. However, the stability and thus bioavailability of these newly formed Fe-Cd mineral phases needs to be assessed thoroughly. Whether phytoremediation or immobilization of Cd in a mineral with reduced Cd bioavailability are feasible mechanisms to reduce toxic effects of Cd in the environment remains to be determined.

Safety and Immunological Efficacy of a DNA Vaccine Encoding the Androgen Receptor Ligand-Binding Domain (AR-LBD).

PubMed

Olson, Brian M; Bradley, Eric S; Sawicki, Thomas; Zhong, Weixiong; Ranheim, Erik A; Bloom, Jordan E; Colluru, Viswa T; Johnson, Laura E; Rekoske, Brian T; Eickhoff, Jens C; McNeel, Douglas G

2017-05-01

The androgen receptor (AR) is a key oncogenic driver of prostate cancer, and has been the primary focus of prostate cancer treatment for several decades. We have previously demonstrated that the AR is also an immunological target antigen, recognized in patients with prostate cancer, and targetable by means of vaccines in rodent models with delays in prostate tumor growth. The current study was performed to determine the safety and immunological efficacy of a GMP-grade plasmid DNA vaccine encoding the ligand-binding domain (LBD) of the AR, pTVG-AR. Groups of male mice (n = 6-10 per group) were evaluated after four or seven immunizations, using different schedules and inclusion of GM-CSF as a vaccine adjuvant. Animals were assessed for toxicity using gross observations, pathological analysis, and analysis of serum chemistries. Animals were analyzed for evidence of vaccine-augmented immunity by tetramer analysis. Survival studies using different immunization schedules and inclusion of GM-CSF were conducted in an autochthonous genetically engineered mouse model. No significant toxicities were observed in terms of animal weights, histopathology, hematological changes, or changes in serum chemistries, although there was a trend to lower serum glucose in animals treated with the vaccine. There was specifically no evidence of toxicity in other tissues that express AR, including liver, muscle, hematopoietic, and brain. Vaccination was found to elicit AR LBD-specific CD8+ T cells. In a subsequent study of tumor-bearing animals, animals treated with vaccine had prolonged survival compared with control-immunized mice. These studies demonstrate that, in immunocompetent mice expressing the target antigen, immunization with the pTVG-AR vaccine was both safe and effective in eliciting AR-specific cellular immune responses, and prolonged the survival of prostate tumor-bearing mice. These findings support the clinical evaluation of pTVG-AR in patients with recurrent prostate cancer. Prostate 77:812-821, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Cutaneous antigen-stimulating lymphokine production by lymphocytes of patients with progressive systemic sclerosis (scleroderma).

PubMed Central

Kondo, H; Rabin, B S; Rodnan, G P

1976-01-01

Cell-mediated immunity to skin extracts was studied by the macrophage migration inhibition test, lymphocyte transformation, and direct cytotoxicity to skin fibroblasts, in normal individuals and patients with progressive systemic sclerosis. The latter included 18 individuals with diffuse scleroderma and 12 with the CREST syndrome, a variant form of systemic sclerosis in which there is more limited involvement of the skin. Controls consisted of 13 patients with other connective tissue diseases and 16 normal individuals. Phosphate-buffered saline and 3 M KCl extracts of both normal and sclerodermatous skin were used as antigens. No evidence of lymphocyte reactivity was found by the lymphocyte transformation and direct cytotoxicity test procedures. However, the lymphocytes of patients with diffuse scleroderma did respond to extracts of both normal and sclerodermatous skin in the migration inhibition assay. 10 of 16 patients (62.5%) had migration indices below 2 SD of the normal range, 1 of 10 CREST patients and 1 of 13 patients with other connective tissue diseases showed similar reactivity. Antisera specific for immunoglobulin-bearing lymphocytes (B lymphocytes) and T lymphocytes were used to characterize the lymphocytes found in skin biopsies of patients with diffuse scleroderma. T lymphocytes made up the majority of lymphocytes in the skin infiltrates. These findings suggest that lymphocytes sensitized to skin extracts are present in patients with diffuse scleroderma. The cell-mediated immune reaction to skin antigens may be a factor in the pathogenesis of diffuse scleroderma. Images PMID:791970

Convection enhanced delivery of carmustine to the murine brainstem: a feasibility study.

PubMed

Sewing, A Charlotte P; Caretti, Viola; Lagerweij, Tonny; Schellen, Pepijn; Jansen, Marc H A; van Vuurden, Dannis G; Idema, Sander; Molthoff, Carla F M; Vandertop, W Peter; Kaspers, Gertjan J L; Noske, David P; Hulleman, Esther

2014-12-30

Systemic delivery of therapeutic agents remains ineffective against diffuse intrinsic pontine glioma (DIPG), possibly due to an intact blood-brain-barrier (BBB) and to dose-limiting toxicity of systemic chemotherapeutic agents. Convection-enhanced delivery (CED) into the brainstem may provide an effective local delivery alternative for DIPG patients. The aim of this study is to develop a method to perform CED into the murine brainstem and to test this method using the chemotherapeutic agent carmustine (BiCNU). To this end, a newly designed murine CED catheter was tested in vitro and in vivo. After determination of safety and distribution, mice bearing VUMC-DIPG-3 and E98FM-DIPG brainstem tumors were treated with carmustine dissolved in DW 5% or carmustine dissolved in 10% ethanol. Our results show that CED into the murine brainstem is feasible and well tolerated by mice with and without brainstem tumors. CED of carmustine dissolved in 5% DW increased median survival of mice with VUMC-DIPG-3 and E98FM-DIPG tumors with 35% and 25% respectively. Dissolving carmustine in 10% ethanol further improved survival to 45% in mice with E98FM-DIPG tumors. Since genetically engineered and primary DIPG models are currently only available in mice, murine CED studies have clear advantages over CED studies in other animals. CED in the murine brainstem can be performed safely, is well tolerated and can be used to study efficacy of chemotherapeutic agents orthotopically. These results set the foundation for more CED studies in murine DIPG models. Copyright © 2014 Elsevier B.V. All rights reserved.

Understanding long-term silver release from surface modified porous titanium implants.

PubMed

Shivaram, Anish; Bose, Susmita; Bandyopadhyay, Amit

2017-08-01

Prevention of orthopedic device related infection (ODRI) using antibiotics has met with limited amount of success and is still a big concern during post-surgery. As an alternative, use of silver as an antibiotic treatment to prevent surgical infections is being used due to the well-established antimicrobial properties of silver. However, in most cases silver is used in particulate form with wound dressings or with short-term devices such as catheters but not with load-bearing implants. We hypothesize that strongly adherent silver to load-bearing implants can offer longer term solution to infection in vivo. Keeping that in mind, the focus of this study was to understand the long term release study of silver ions for a period of minimum 6months from silver coated surface modified porous titanium implants. Implants were fabricated using a LENS™ system, a powder based additive manufacturing technique, with at least 25% volume porosity, with and without TiO 2 nanotubes in phosphate buffer saline (pH 7.4) to see if the total release of silver ions is within the toxic limit for human cells. Considering the fact that infection sites may reduce the local pH, silver release was also studied in acetate buffer (pH 5.0) for a period of 4weeks. Along with that, the osseointegrative properties as well as cytotoxicity of porous titanium implants were assessed in vivo for a period of 12weeks using a rat distal femur model. In vivo results indicate that porous titanium implants with silver coating show comparable, if not better, biocompatibility and bonding at the bone-implant interface negating any concerns related to toxicity related to silver to normal cells. The current research is based on our recently patented technology, however focused on understanding longer-term silver release to mitigate infection related problems in load-bearing implants that can even arise several months after the surgery. Prevention of orthopedic device related infection using antibiotics has met with limited success and is still a big concern during post-surgery. Use of silver as an antibiotic treatment to prevent surgical infections is being explored due to the well-established antimicrobial properties of silver. However, in most cases silver is used in particulate form with wound dressings or with short-term devices such as catheters but not with load-bearing implants. We hypothesize that strongly adherent silver to load-bearing implants can offer longer-term solution towards infection in vivo. Keeping that in mind, the focus of this study was to understand the long-term release of silver ions, for a period of minimum 6months, from silver coated surface modified porous titanium implants. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

A Potential Bone-Targeting Hypotoxic Platinum(II) Complex with an Unusual Cytostatic Mechanism toward Osteosarcoma Cells.

PubMed

Zhang, Zhenqin; Zhu, Zhenzhu; Luo, Cheng; Zhu, Chengcheng; Zhang, Changli; Guo, Zijian; Wang, Xiaoyong

2018-03-19

Osteosarcoma (OS) is the most common primary pediatric bone tumor lethal to children and adolescents. Chemotherapeutic agents such as cisplatin are not effective for OS because of their poor accessibility to this cancer and severe systemic toxicity. In this study, a lipophilic platinum(II) complex bearing a bisphosphonate bone-targeting moiety, cis-[PtL(NH 3 ) 2 Cl]NO 3 {BPP; L = tetraethyl [2-(pyridin-2-yl)ethane-1,1-diyl]bisphosphonate}, was prepared and characterized by NMR, electrospray ionization mass spectrometry, and single-crystal X-ray crystallography. The cytotoxicity of BPP toward OS cell lines U2OS and MG-63 was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. BPP exhibits moderate inhibition against U2OS cells through a mechanism involving both DNA binding and a mevalonate pathway. The acute toxicity of BPP to mice is 7-fold lower than that of cisplatin. The relative low systemic toxicity may result from the steric hindrance of the ligand, which blocks BPP approaching the bases of DNA. The results suggest that incorporating bisphosphonates into a platinum complex not only enhances its bone-targeting property but also minimizes its reactivity toward DNA and thereby lowers the systematic toxicity of the complex. The diminished cytotoxicity of BPP could be compensated for by increasing the therapeutic dose with marginal harm. This strategy provides a new possibility for overcoming the ineffectiveness and systemic toxicity of platinum drugs in the treatment of OS.

Tumor characterization in small animals using magnetic resonance-guided dynamic contrast enhanced diffuse optical tomography

NASA Astrophysics Data System (ADS)

Lin, Yuting; Thayer, Dave; Nalcioglu, Orhan; Gulsen, Gultekin

2011-10-01

We present a magnetic resonance (MR)-guided near-infrared dynamic contrast enhanced diffuse optical tomography (DCE-DOT) system for characterization of tumors using an optical contrast agent (ICG) and a MR contrast agent [Gd-diethylenetriaminepentaacetic acid (DTPA)] in a rat model. Both ICG and Gd-DTPA are injected and monitored simultaneously using a combined MRI-DOT system, resulting in accurate co-registration between two imaging modalities. Fisher rats bearing R3230 breast tumor are imaged using this hybrid system. For the first time, enhancement kinetics of the exogenous contrast ICG is recovered from the DCE-DOT data using MR anatomical a priori information. As tumors grow, they undergo necrosis and the tissue transforms from viable to necrotic. The results show that the physiological changes between viable and necrotic tissue can be differentiated more accurately based on the ICG enhancement kinetics when MR anatomical information is utilized.

The formation of molecules in interstellar clouds from singly and multiply ionized atoms

NASA Technical Reports Server (NTRS)

Langer, W. D.

1978-01-01

The suggestion is considered that multiply ionized atoms produced by K- and L-shell X-ray ionization and cosmic-ray ionization can undergo ion-molecule reactions and also initiate molecule production. The role of X-rays in molecule production in general is discussed, and the contribution to molecule production of the C(+) radiative association with hydrogen is examined. Such gas-phase reactions of singly and multiply ionized atoms are used to calculate molecular abundances of carbon-, nitrogen-, and oxygen-bearing species. The column densities of the molecules are evaluated on the basis of a modified version of previously developed isobaric cloud models. It is found that reactions of multiply ionized carbon with H2 can contribute a significant fraction of the observed CH in diffuse interstellar clouds in the presence of diffuse X-ray structures or discrete X-ray sources and that substantial amounts of CH(+) can be produced under certain conditions.

Diffusion models for corona formation in metagabbros from the Western Grenville Province, Canada

NASA Astrophysics Data System (ADS)

Grant, Shona M.

1988-01-01

Metagabbro bodies in SW Grenville Province display a variety of disequilibrium corona textures between spinel-clouded plagioclase and primary olivine or opaque oxide. Textural evidence favours a single-stage, subsolidus origin for the olivine coronas and diffusive mass transfer is believed to have been the rate-controlling process. Irreversible thermodynamics have been used to model two different garnet symplectite-bearing corona sequences in terms of steady state diffusion. In the models the flux of each component is related to the chemical potential gradients of all diffusing species by the Onsager or L-coefficients for diffusion. These coefficients are analogous to experimentally determined diffusion coefficients ( d), but relate the flux of components to chemical potential rather than concentration gradients. The major constraint on the relative values of Onsager coefficients comes from the observed mole fraction, X, of garnet in the symplectites; in (amph-gt) symplectites X {Gt/Sym}˜0.80, compared with ˜0.75 in (cpx-gt) symplectites. Several models using simple oxide components, and two different modifications of the reactant plagioclase composition, give the following qualitative results: the very low mobility of aluminium appears to control the rate of corona formation. Mg and Fe have similar mobility, and Mg can be up to 6 8 times more mobile than sodium. Determination of calcium mobility is problematical because of a proposed interaction with cross-coefficient terms reflecting “uphill” Ca-diffusion, i.e., calcium diffusing up its own chemical potential gradient. If these terms are not introduced, it is difficult to generate the required proportions of garnet in the symplectite. However, at moderate values of the cross-coefficient ratios, Mg can be up to 4 6 times more mobile than calcium ( L MgMg/LCaCa<4 6) and calcium must be 3 4 times more mobile than aluminium ( L CaCa/LAlAl>3).

Transformable liquid-metal nanomedicine

PubMed Central

Lu, Yue; Hu, Quanyin; Lin, Yiliang; Pacardo, Dennis B.; Wang, Chao; Sun, Wujin; Ligler, Frances S.; Dickey, Michael D.; Gu, Zhen

2015-01-01

To date, numerous inorganic nanocarriers have been explored for drug delivery systems (DDSs). However, the clinical application of inorganic formulations has often been hindered by their toxicity and failure to biodegrade. We describe here a transformable liquid-metal nanomedicine, based on a core–shell nanosphere composed of a liquid-phase eutectic gallium-indium core and a thiolated polymeric shell. This formulation can be simply produced through a sonication-mediated method with bioconjugation flexibility. The resulting nanoparticles loaded with doxorubicin (Dox) have an average diameter of 107 nm and demonstrate the capability to fuse and subsequently degrade under a mildly acidic condition, which facilitates release of Dox in acidic endosomes after cellular internalization. Equipped with hyaluronic acid, a tumour-targeting ligand, this formulation displays enhanced chemotherapeutic inhibition towards the xenograft tumour-bearing mice. This liquid metal-based DDS with fusible and degradable behaviour under physiological conditions provides a new strategy for engineering theranostic agents with low toxicity. PMID:26625944

Alzheimer disease

PubMed Central

Nussbaum, Justin M.; Seward, Matthew E.; Bloom, George S.

2013-01-01

Alzheimer disease (AD) has traditionally been thought to involve the misfolding and aggregation of two different factors that contribute in parallel to pathogenesis: amyloid-β (Aβ) peptides, which represent proteolytic fragments of the transmembrane amyloid precursor protein, and tau, which normally functions as a neuronally enriched, microtubule-associated protein that predominantly accumulates in axons. Recent evidence has challenged this model, however, by revealing numerous functional interactions between Aβ and tau in the context of pathogenic mechanisms for AD. Moreover, the propagation of toxic, misfolded Aβ and tau bears a striking resemblance to the propagation of toxic, misfolded forms of the canonical prion protein, PrP, and misfolded Aβ has been shown to induce tau misfolding in vitro through direct, intermolecular interaction. In this review we discuss evidence for the prion-like properties of both Aβ and tau individually, as well as the intriguing possibility that misfolded Aβ acts as a template for tau misfolding in vivo. PMID:22965142

Transformable liquid-metal nanomedicine

NASA Astrophysics Data System (ADS)

Lu, Yue; Hu, Quanyin; Lin, Yiliang; Pacardo, Dennis B.; Wang, Chao; Sun, Wujin; Ligler, Frances S.; Dickey, Michael D.; Gu, Zhen

2015-12-01

To date, numerous inorganic nanocarriers have been explored for drug delivery systems (DDSs). However, the clinical application of inorganic formulations has often been hindered by their toxicity and failure to biodegrade. We describe here a transformable liquid-metal nanomedicine, based on a core-shell nanosphere composed of a liquid-phase eutectic gallium-indium core and a thiolated polymeric shell. This formulation can be simply produced through a sonication-mediated method with bioconjugation flexibility. The resulting nanoparticles loaded with doxorubicin (Dox) have an average diameter of 107 nm and demonstrate the capability to fuse and subsequently degrade under a mildly acidic condition, which facilitates release of Dox in acidic endosomes after cellular internalization. Equipped with hyaluronic acid, a tumour-targeting ligand, this formulation displays enhanced chemotherapeutic inhibition towards the xenograft tumour-bearing mice. This liquid metal-based DDS with fusible and degradable behaviour under physiological conditions provides a new strategy for engineering theranostic agents with low toxicity.

Specific aquaporins facilitate the diffusion of hydrogen peroxide across membranes.

PubMed

Bienert, Gerd P; Møller, Anders L B; Kristiansen, Kim A; Schulz, Alexander; Møller, Ian M; Schjoerring, Jan K; Jahn, Thomas P

2007-01-12

The metabolism of aerobic organisms continuously produces reactive oxygen species. Although potentially toxic, these compounds also function in signaling. One important feature of signaling compounds is their ability to move between different compartments, e.g. to cross membranes. Here we present evidence that aquaporins can channel hydrogen peroxide (H2O2). Twenty-four aquaporins from plants and mammals were screened in five yeast strains differing in sensitivity toward oxidative stress. Expression of human AQP8 and plant Arabidopsis TIP1;1 and TIP1;2 in yeast decreased growth and survival in the presence of H2O2. Further evidence for aquaporin-mediated H2O2 diffusion was obtained by a fluorescence assay with intact yeast cells using an intracellular reactive oxygen species-sensitive fluorescent dye. Application of silver ions (Ag+), which block aquaporin-mediated water diffusion in a fast kinetics swelling assay, also reversed both the aquaporin-dependent growth repression and the H2O2-induced fluorescence. Our results present the first molecular genetic evidence for the diffusion of H2O2 through specific members of the aquaporin family.

A network model of successive partitioning-limited solute diffusion through the stratum corneum.

PubMed

Schumm, Phillip; Scoglio, Caterina M; van der Merwe, Deon

2010-02-07

As the most exposed point of contact with the external environment, the skin is an important barrier to many chemical exposures, including medications, potentially toxic chemicals and cosmetics. Traditional dermal absorption models treat the stratum corneum lipids as a homogenous medium through which solutes diffuse according to Fick's first law of diffusion. This approach does not explain non-linear absorption and irregular distribution patterns within the stratum corneum lipids as observed in experimental data. A network model, based on successive partitioning-limited solute diffusion through the stratum corneum, where the lipid structure is represented by a large, sparse, and regular network where nodes have variable characteristics, offers an alternative, efficient, and flexible approach to dermal absorption modeling that simulates non-linear absorption data patterns. Four model versions are presented: two linear models, which have unlimited node capacities, and two non-linear models, which have limited node capacities. The non-linear model outputs produce absorption to dose relationships that can be best characterized quantitatively by using power equations, similar to the equations used to describe non-linear experimental data.

Extension and gold mineralisation in the hanging walls of active convergent continental shear zones

NASA Astrophysics Data System (ADS)

Upton, Phaedra; Craw, Dave

2014-07-01

Orogenic gold-bearing quartz veins form in mountain belts adjacent to convergent tectonic boundaries. The vein systems, hosted in extensional structures within compressively deformed rocks, are a widespread feature of these orogens. In many cases the extensional structures that host gold-bearing veins have been superimposed on, and locally controlled by, compressional structures formed within the convergent orogen. Exploring these observations within the context of a three-dimensional mechanical model allows prediction of mechanisms and locations of extensional zones within convergent orogens. Our models explore the effect of convergence angle and mid-crustal strength on stress states and compare them to the Southern Alps and Taiwan. The dilatation zones coincide with the highest mountains, in the hanging walls of major plate boundary faults, and can extend as deep as the brittle-ductile transition. Extensional deformation is favoured in the topographic divide region of oblique orogens with mid-lower crustal rheology that promotes localisation rather than diffuse deformation. In the near surface, topography influences the stress state to a depth approximately equal to the topographic relief, bringing the rock closer to failure and rotating σ1 to near vertical. The distribution of gold-bearing extensional veins may indicate the general position of the topographic divide within exhumed ancient orogens.

Diffusive parameters of tritiated water and uranium in chalk

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

Descostes, M.; UMR 8587 CEA, Universite d'Evry, CNRS,; Pili, E.

2012-07-15

The Cretaceous Chalk of North-western Europe exhibits a double porosity (matrix and fracture) providing pathways for both slow and rapid flow of water. The present study aims at understanding and predicting the contaminant transfer properties through a significant section of this formation, with a particular emphasis on diffusion. This requires to study the nature of porosity and to perform diffusion experiments in representative samples using uranium and tritiated water (HTO), respectively taken as a reactive tracer and an inert one. The diffusive parameters, i.e. the accessible porosity and the effective diffusion coefficient were determined. Additional information was obtained with mercurymore » porosimetry, gravimetric water content, textural and mineralogical characterization. The diffusion tests performed with HTO appear to be the best method to measure the total accessible porosity in any type of porous media, especially those having large pore size distributions. Our study demonstrates that classical gravimetric water content measurements are not sensitive to the reduction in pore size as opposed to HTO diffusion tests because capillary water is not extracted by conventional gravimetric method but can still be probed by diffusion experiments. We found effective diffusion coefficients D{sub e}(U(VI)) near 4 x 10{sup -10} m{sup 2}s{sup -1}). The slower migration of U(VI) compared to HTO indicates sorption, with R{sub d}(U(VI)) from 100 to 360 mL g{sup -1}. These values are one order of magnitude larger than other determinations of the U(VI) sorption coefficient because only the matrix porosity is concerned here. The migration of U(VI) in chalk is only limited by sorption on ancillary Fe-Pb-bearing minerals. Transport of HTO and U(VI) is independent of the porosity distribution. Uranium diffusion in the chalk matrix porosity is fast enough to allow the total invasion of the pore space within characteristic time scales of the order of 1000 years. This results in a partitioning of uranium velocities in fracture flow and matrix flow proportionally to the respective fracture and matrix porosities. (authors)« less

[Protective effect of polysaccharides extracts from corn silk against cyclophosphamide induced host damages in mice bearing H22 tumors].

PubMed

Wu, Xian-chuang; Du, Gang-jun; Song, Xiao-yong; Zhang, Yong-zhou; Liu, Yu-xin

2014-10-01

To study the protective effect of polysaccharides from corn silk (PCS) against cyclophosphamide (CTX) induced host damages in mice bearing H22 tumors. The ascitic and solid tumor bearing mice model were established to investigate the anti-tumor effects of different dose of PCS (100, 200 and 300 mg/kg). The effects of PCS alone and with combination of CTX on tumor weight, survival time, thymus and spleen index, white blood cell, nucleated cell of marrow, serum ALT and AST level were tested. The high-dose PCS (300 mg/kg) had significant inhibitory effects on tumor. After combination with CTX, the tumor inhibitory ratio was enhanced to 68.71%, the survival time of tumor-burdened ascites tumor mice was significantly prolonged to 72.07% compared with CTX group. The Q value of combination group was 0.997. Thymus and spleen index, white blood cell, nucleated cell of marrow decreased by CTX were ameliorated significantly. The level of ALT and AST increased by CTX were reduced by combination with PCS. PCS has a potent inhibitory effect on the growth of implanted H22 tumors in mice and has a synergetic effect and an attenuated toxic effect in combination with CTX.

Determination of the Chronic Mammalian Toxicological Effects of RDX. Acute Dermal Toxicity Test of Hexehydro-1,3,5-Trinitro-1,3,5-Triazine (RDX) in Rabbits

DTIC Science & Technology

1984-08-01

Typist B. Letica Verified: L_. Pathologist - Date 20 Study Nlumnber L6121.10 Dose (mg/1) Test Animal Number 15 * Accession Number 81-7176 Microscopic...Diffusemoderate necrosis of mucosal epithelium. Mild, diffuse accumulation of inflammatory cells in mucosa and submucosa Typist B. Letica Verified: tk

Background Paper on Aerospace & Missile Needs

DTIC Science & Technology

2006-05-01

Micro- welding based coatings Trivalent chromium plated coatings Nano-composite Ni-P and Co-P based plated coatings Thermal diffusion coatings Plasma...working in conjunction with Advanced Surfaces and Processes, Inc. to determine the applicability of another type of ESD process. Trivalent Chromium ...Plating: Trivalent chromium is considered to be much less toxic than hexavalent chromium . Consequently, trivalent chromium coatings are being

Thirteen Week Oral Toxicity Study of WR242511 in Rats. Volume 1

DTIC Science & Technology

1994-01-14

hypercholesterolemia and hypertriglyceridemia seen in high dose females, as previously discussed. Heptatobiliary changes were suggested by significant elevations in...lung (alveolar histiocytosis) lesions. Severe thymic lymphocyte depletion was also observed in these animals where the thymus could be identified...this animal, but it was attributed to the severe and diffuse chronic-active inflammation. As indicated above, treatment-related histopathologic

Ammonia toxicity: from head to toe?

PubMed

Dasarathy, Srinivasan; Mookerjee, Rajeshwar P; Rackayova, Veronika; Rangroo Thrane, Vinita; Vairappan, Balasubramaniyan; Ott, Peter; Rose, Christopher F

2017-04-01

Ammonia is diffused and transported across all plasma membranes. This entails that hyperammonemia leads to an increase in ammonia in all organs and tissues. It is known that the toxic ramifications of ammonia primarily touch the brain and cause neurological impairment. However, the deleterious effects of ammonia are not specific to the brain, as the direct effect of increased ammonia (change in pH, membrane potential, metabolism) can occur in any type of cell. Therefore, in the setting of chronic liver disease where multi-organ dysfunction is common, the role of ammonia, only as neurotoxin, is challenged. This review provides insights and evidence that increased ammonia can disturb many organ and cell types and hence lead to dysfunction.

Synthesis and characterization of polylactide/doxorubicin/magnetic nanoparticles composites for drug delivery

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

Mhlanga, Nikiwe; Ray, Suprakas Sinha; DST/CSIR National Centre for Nanostructured Materials, Council for Scientific and Industrial Research, Pretoria, 0001

Magnetic iron oxide nanoparticles have potential to transform conventional therapeutics, through targeted delivery by external magnetic field modulation. Conventional drug delivery lacks specificity; both normal and infected cells are exposed to toxic drugs. Consequently, the toxicity towards healthy cells leads to detrimental side effects which are formidable. However, iron oxide research in biomedicine has been hindered by their lack of stability. This study reports on the stabilization of iron oxide by polylactide (PLA). Besides affording stable iron oxide, PLA is also good for sustained delivery of the drug. PLA/doxorubicin/magnetic nanoparticles (PLA/DOX/MNPs) spheres were synthesized by solvent evaporation method and DOXmore » anticancer drug was encapsulated. The spheres were characterized using scanning electron microscope, Fourier transform infrared microscope, thermogravimetric analyzer and UV-visible spectroscopy, which ascertained formation of the anticipated spheres and incorporation of DOX. In vitro drug release studies were carried out in both phosphate buffer (pH 7.4) and acetate buffer (pH 4.6) and they showed the same trend in both mediums. Drug release kinetics followed Higuchi model, which proved drug release by diffusion via a diffusion gradient.« less

Zinc toxicosis in a free-flying trumpeter swan (Cygnus buccinator)

USGS Publications Warehouse

Carpenter, J.W.; Andrews, G.A.; Beyer, W.N.

2004-01-01

A trumpeter swan (Cygnus buccinator) was observed near it mill pond in Picher, Oklahoma. USA. It became weakened and emaciated after about 1 mo, was captured with little resistance, and taken into captivity for medical care. Serum chemistry results were consistent with hepatic, renal, and muscular damage. Serum zinc concentration was elevated at 11.2 parts per million (ppm). The swan was treated for suspected heavy-metal poisoning, but died overnight. Gross postmortem findings were emaciation and pectoral muscle atrophy. Histopathologic lesions in the pancreas included mild diffuse disruption of acinar architecture, severe diffuse depletion or absence of zymogen granules, occasional apoptotic bodies ics in acinar epithelial cells, and mild interstitial and capsular fibrosis. Zinc concentration in pancreas was 3,200 ppm wet weight, and was similar to that reported in the pancreases of waterfowl known to be killed by zinc toxicity. Zinc concentrations in liver (154 ppm) and kidneys (145 ppm) also were elevated. Acute tubular necrosis of the collecting tubules of the kidneys was also possibly due to zinc toxicity. To the authors' knowledge, this is the first confirmed case of zinc poisoning in a trumpeter swan associated with mining wastes..

Long-Term Pulmonary Function in Survivors of Childhood Cancer

PubMed Central

Armenian, Saro H.; Landier, Wendy; Francisco, Liton; Herrera, Claudia; Mills, George; Siyahian, Aida; Supab, Natt; Wilson, Karla; Wolfson, Julie A.; Horak, David; Bhatia, Smita

2015-01-01

Purpose This study was undertaken to determine the magnitude of pulmonary dysfunction in childhood cancer survivors when compared with healthy controls and the extent (and predictors) of decline over time. Patients and Methods Survivors underwent baseline (t1) pulmonary function tests, followed by a second comprehensive evaluation (t2) after a median of 5 years (range, 1.0 to 10.3 years). Survivors were also compared with age- and sex-matched healthy controls at t2. Results Median age at cancer diagnosis was 16.5 years (range, 0.2 to 21.9 years), and time from diagnosis to t2 was 17.1 years (range, 6.3 to 40.1 years). Compared with odds for healthy controls, the odds of restrictive defects were increased 6.5-fold (odds ratio [OR], 6.5; 95% CI, 1.5 to 28.4; P < .01), and the odds of diffusion abnormalities were increased 5.2-fold (OR, 5.2; 95% CI, 1.8 to 15.5; P < .01). Among survivors, age younger than 16 years at diagnosis (OR, 3.0; 95% CI, 1.2 to 7.8; P = .02) and exposure to more than 20 Gy chest radiation (OR, 5.6; 95% CI, 1.5 to 21.0; P = .02, referent, no chest radiation) were associated with restrictive defects. Female sex (OR, 3.9; 95% CI, 1.7 to 9.5; P < .01) and chest radiation dose (referent: no chest radiation; ≤ 20 Gy: OR, 6.4; 95% CI, 1.7 to 24.4; P < .01; > 20 Gy: OR, 11.3; 95% CI, 2.6 to 49.5; P < .01) were associated with diffusion abnormalities. Among survivors with normal pulmonary function tests at t1, females and survivors treated with more than 20 Gy chest radiation demonstrated decline in diffusion function over time. Conclusion Childhood cancer survivors exposed to pulmonary-toxic therapy are significantly more likely to have restrictive and diffusion defects when compared with healthy controls. Diffusion capacity declines with time after exposure to pulmonary-toxic therapy, particularly among females and survivors treated with high-dose chest radiation. These individuals could benefit from subsequent monitoring. PMID:25847925

Hemithoracic intensity modulated radiation therapy after pleurectomy/decortication for malignant pleural mesothelioma: toxicity, patterns of failure, and a matched survival analysis.

PubMed

Chance, William W; Rice, David C; Allen, Pamela K; Tsao, Anne S; Fontanilla, Hiral P; Liao, Zhongxing; Chang, Joe Y; Tang, Chad; Pan, Hubert Y; Welsh, James W; Mehran, Reza J; Gomez, Daniel R

2015-01-01

To investigate safety, efficacy, and recurrence after hemithoracic intensity modulated radiation therapy after pleurectomy/decortication (PD-IMRT) and after extrapleural pneumonectomy (EPP-IMRT). In 2009-2013, 24 patients with mesothelioma underwent PD-IMRT to the involved hemithorax to a dose of 45 Gy, with an optional integrated boost; 22 also received chemotherapy. Toxicity was scored with the Common Terminology Criteria for Adverse Events v4.0. Pulmonary function was compared at baseline, after surgery, and after IMRT. Kaplan-Meier analysis was used to calculate overall survival (OS), progression-free survival (PFS), time to locoregional failure, and time to distant metastasis. Failures were in-field, marginal, or out of field. Outcomes were compared with those of 24 patients, matched for age, nodal status, performance status, and chemotherapy, who had received EPP-IMRT. Median follow-up time was 12.2 months. Grade 3 toxicity rates were 8% skin and 8% pulmonary. Pulmonary function declined from baseline to after surgery (by 21% for forced vital capacity, 16% for forced expiratory volume in 1 second, and 19% for lung diffusion of carbon monoxide [P for all = .01]) and declined still further after IMRT (by 31% for forced vital capacity [P=.02], 25% for forced expiratory volume in 1 second [P=.01], and 30% for lung diffusion of carbon monoxide [P=.01]). The OS and PFS rates were 76% and 67%, respectively, at 1 year and 56% and 34% at 2 years. Median OS (28.4 vs 14.2 months, P=.04) and median PFS (16.4 vs 8.2 months, P=.01) favored PD-IMRT versus EPP-IMRT. No differences were found in grade 4-5 toxicity (0 of 24 vs 3 of 24, P=.23), median time to locoregional failure (18.7 months vs not reached, P not calculable), or median time to distant metastasis (18.8 vs 11.8 months, P=.12). Hemithoracic intensity modulated radiation therapy after pleurectomy/decortication produced little high-grade toxicity but led to progressive declines in pulmonary function; OS and PFS were better in PD-IMRT compared with EPP-IMRT. Copyright © 2015 Elsevier Inc. All rights reserved.

Spectral diffusion in poly(para-phenylene)-type polymers with different energetic disorder

NASA Astrophysics Data System (ADS)

Hoffmann, Sebastian T.; Bässler, Heinz; Koenen, Jan-Moritz; Forster, Michael; Scherf, Ullrich; Scheler, Esther; Strohriegl, Peter; Köhler, Anna

2010-03-01

We have employed quasicontinuous fluorescence and phosphorescence spectroscopy within a temperature range between 10 and 500 K to monitor the spectral diffusion of singlet and triplet excitons in a series of π -conjugated polymers. We investigated (i) how spectral diffusion is controlled by the degree of energetic disorder present in the amorphous film (that is reflected by the inhomogeneous broadening of the photoluminescence spectra) and (ii) how this process depends on the range of the electronic coupling (by comparing singlet exciton diffusion via long-range Förster transfer against triplet exciton diffusion by short-range Dexter transfer). For singlets, we find that the fluorescence spectra bear out a bathochromic shift upon cooling the sample down to a critical temperature below which the shift saturates. This bathochromic shift is a signature of spectral relaxation. Random-walk theory applied to excitation transport within a Gaussian density-of-states distribution is both necessary and sufficient to rationalize the experimental results in a quantitative fashion. The same behavior is observed for triplets in weakly disordered systems, such as in a polymer containing platinum in the main chain and a ladder-type polyphenylene. In contrast we observe a hypsochromic shift of the phosphorescence spectra below a characteristic temperature for triplets in systems with at least moderate energetic disorder. The hypsochromic shift proves that triplet exciton relaxation becomes frustrated because thermally activated exciton jumps that otherwise promote spectral diffusion become progressively frozen out. The frustration effect is controlled by the jump distance and thus it is specific for triplet excitations that migrate via short-range coupling among strongly localized states as compared to singlet excitons.

Toxic and inhibitory effects of trichloroethylene aerobic co-metabolism on phenol-grown aerobic granules.

PubMed

Zhang, Yi; Tay, JooHwa

2015-04-09

Aerobic granule, a form of microbial aggregate, exhibits good potential in degrading toxic and recalcitrant substances. In this study, the inhibitory and toxic effects of trichloroethylene (TCE), a model compound for aerobic co-metabolism, on phenol-grown aerobic granules were systematically studied, using respiratory activities after exposure to TCE as indicators. High TCE concentration did not exert positive or negative effects on the subsequent endogenous respiration rate or phenol dependent specific oxygen utilization rate (SOUR), indicating the absence of solvent stress and induction effect on phenol-hydroxylase. Phenol-grown aerobic granules exhibited a unique response to TCE transformation product toxicity, that small amount of TCE transformation enhanced the subsequent phenol SOUR. Granules that had transformed between 1.3 and 3.7 mg TCE gSS(-1) showed at most 53% increase in the subsequent phenol SOUR, and only when the transformation exceeded 6.6 mg TCE gSS(-1) did the SOUR dropped below that of the control. This enhancing effect was found to sustain throughout several phenol dosages, and TCE transformation below the toxicity threshold also lessened the granules' sensitivity to higher phenol concentration. The unique toxic effect was possibly caused by the granule's compact structure as a protection barrier against the diffusive transformation product(s) of TCE co-metabolism. Copyright © 2015 Elsevier B.V. All rights reserved.

Supercritical-Carbon Dioxide Fluid Extract from Chrysanthemum indicum Enhances Anti-Tumor Effect and Reduces Toxicity of Bleomycin in Tumor-Bearing Mice

PubMed Central

Yang, Hong-Mei; Sun, Chao-Yue; Liang, Jia-Li; Xu, Lie-Qiang; Zhang, Zhen-Biao; Luo, Dan-Dan; Chen, Han-Bin; Huang, Yong-Zhong; Wang, Qi; Lee, David Yue-Wei; Yuan, Jie; Li, Yu-Cui

2017-01-01

Bleomycin (BLM), a family of anti-tumor drugs, was reported to exhibit severe side effects limiting its usage in clinical treatment. Therefore, finding adjuvants that enhance the anti-tumor effect and reduce the detrimental effect of BLM is a prerequisite. Chrysanthemum indicum, an edible flower, possesses abundant bioactivities; the supercritical-carbon dioxide fluid extract from flowers and buds of C. indicum (CISCFE) have strong anti-inflammatory, anti-oxidant, and lung protective effects. However, the role of CISCFE combined with BLM treatment on tumor-bearing mice remains unclear. The present study aimed to investigate the potential synergistic effect and the underlying mechanism of CISCFE combined with BLM in the treatment of hepatoma 22 (H22) tumor-bearing mice. The results suggested that the oral administration of CISCFE combined with BLM could markedly prolong the life span, attenuate the BLM-induced pulmonary fibrosis, suppress the production of pro-inflammatory cytokines (interleukin-6), tumor necrosis factor-α, activities of myeloperoxidase, and malondiadehyde. Moreover, CISCFE combined with BLM promoted the ascites cell apoptosis, the activities of caspases 3 and 8, and up-regulated the protein expression of p53 and down-regulated the transforming growth factor-β1 by activating the gene expression of miR-29b. Taken together, these results indicated that CISCFE could enhance the anti-cancer activity of BLM and reduce the BLM-induced pulmonary injury in H22 tumor-bearing mice, rendering it as a potential adjuvant drug with chemotherapy after further investigation in the future. PMID:28245556

Supercritical-Carbon Dioxide Fluid Extract from Chrysanthemum indicum Enhances Anti-Tumor Effect and Reduces Toxicity of Bleomycin in Tumor-Bearing Mice.

PubMed

Yang, Hong-Mei; Sun, Chao-Yue; Liang, Jia-Li; Xu, Lie-Qiang; Zhang, Zhen-Biao; Luo, Dan-Dan; Chen, Han-Bin; Huang, Yong-Zhong; Wang, Qi; Lee, David Yue-Wei; Yuan, Jie; Li, Yu-Cui

2017-02-24

Bleomycin (BLM), a family of anti-tumor drugs, was reported to exhibit severe side effects limiting its usage in clinical treatment. Therefore, finding adjuvants that enhance the anti-tumor effect and reduce the detrimental effect of BLM is a prerequisite. Chrysanthemum indicum , an edible flower, possesses abundant bioactivities; the supercritical-carbon dioxide fluid extract from flowers and buds of C. indicum (CI SCFE ) have strong anti-inflammatory, anti-oxidant, and lung protective effects. However, the role of CI SCFE combined with BLM treatment on tumor-bearing mice remains unclear. The present study aimed to investigate the potential synergistic effect and the underlying mechanism of CI SCFE combined with BLM in the treatment of hepatoma 22 (H22) tumor-bearing mice. The results suggested that the oral administration of CI SCFE combined with BLM could markedly prolong the life span, attenuate the BLM-induced pulmonary fibrosis, suppress the production of pro-inflammatory cytokines (interleukin-6), tumor necrosis factor-α, activities of myeloperoxidase, and malondiadehyde. Moreover, CI SCFE combined with BLM promoted the ascites cell apoptosis, the activities of caspases 3 and 8, and up-regulated the protein expression of p53 and down-regulated the transforming growth factor-β1 by activating the gene expression of miR-29b. Taken together, these results indicated that CI SCFE could enhance the anti-cancer activity of BLM and reduce the BLM-induced pulmonary injury in H22 tumor-bearing mice, rendering it as a potential adjuvant drug with chemotherapy after further investigation in the future.

Spectral reflectance properties (0.4-2.5 um) of secondary Fe-oxide, Fe-hydroxide, and Fe-sulfate-hydrate minerals associated with sulfide-bearing mine waste

USGS Publications Warehouse

Crowley, J.K.; Williams, D.E.; Hammarstrom1, J.M.; Piatak, N.; Mars, J.C.; Chou, I-Ming

2006-01-01

Fifteen Fe-oxide, Fe-hydroxide, and Fe-sulphate-hydrate mineral species commonly associated with sulphide bearing mine wastes were characterized by using X-ray powder diffraction and scanning electron microscope methods. Diffuse reflectance spectra of the samples show diagnostic absorption features related to electronic processes involving ferric and/or ferrous iron, and to vibrational processes involving water and hydroxyl ions. Such spectral features enable field and remote sensing based studies of the mineral distributions. Because secondary minerals are sensitive indicators of pH, Eh, relative humidity, and other environmental conditions, spectral mapping of these minerals promises to have important applications to mine waste remediation studies. This report releases digital (ascii) spectra (spectral_data_files.zip) of the fifteen mineral samples to facilitate usage of the data with spectral libraries and spectral analysis software. The spectral data are provided in a two-column format listing wavelength (in micrometers) and reflectance, respectively.

Photodynamic efficiency of a chlorophyll-a derivative in vitro and in vivo.

PubMed

Zhang, Xiang-Hua; Zhang, Li-Jun; Sun, Jing-Jian; Yan, Yi-Jia; Zhang, Li-Xin; Chen, Na; Chen, Zhi-Long

2016-07-01

This paper reports the antitumor activity of a chlorophyll-a derivative, 2-[1-hydroxyethyl]-2-devinylpyropheophorbide-a (HEPa). Photophysical characteristics of HEPa were measured. And its cytotoxicity, intracellular localization, biodistribution, efficiency of photodynamic therapy (PDT), histological analysis were investigated using human bile duct carcinoma cells (QBC-939) and QBC-939 tumor bearing BABL/c nude mice as animal model. The results showed that HEPa was localized mainly within the cytoplasmic region and partially in lysosome. Biodistribution of HEPa in QBC-939 tumor bearing BABL/c nude mice showed its fast rate of clearance and high tumor selectivity. In vitro, HEPa had low dark toxicity and high photoxicity against QBC-939 cells. The inhibition rate of QBC-939 tumor could increase up to 92.3%, and H&E staining confirmed that HEPa could cause serious damage to the tumor with light dose of 100J/cm(2), implying that HEPa has potential to be a new antitumor candidate for photodynamic therapy (PDT). Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The role of private pesticide vendors in preventing access to pesticides for self-poisoning in rural Sri Lanka.

PubMed

Weerasinghe, Manjula; Pearson, Melissa; Peiris, Ravi; Dawson, Andrew H; Eddleston, Michael; Jayamanne, Shaluka; Agampodi, Suneth; Konradsen, Flemming

2014-04-01

In 15% to 20% of self-poisoning cases, the pesticides used are purchased from shops just prior to ingestion. We explored how pesticide vendors interacted with customers at risk of self-poisoning to identify interventions to prevent such poisonings. Two strategies were specifically discussed: selling pesticides only to farmers bearing identity cards or customers bearing pesticide 'prescriptions'. Vendors reported refusing to sell pesticides to people thought to be at risk of self-poisoning, but acknowledged the difficulty of distinguishing them from legitimate customers; vendors also stated they did want to help to improve identification of such customers. The community did not blame vendors when pesticides used for self-poison were purchased from their shops. Vendors have already taken steps to restrict access, including selling low toxic products, counselling and asking customer to return the next day. However, there was little support for the proposed interventions of 'identity cards' and 'prescriptions'. Novel public health approaches are required to complement this approach.

Risk factors for treatment-related adverse events in cancer-bearing dogs receiving piroxicam.

PubMed

Eichstadt, L R; Moore, G E; Childress, M O

2017-12-01

Piroxicam has antitumour effects in dogs with cancer, although side effects may limit its use. The purpose of this study was to retrospectively identify factors predisposing cancer-bearing dogs to adverse events (AEs) following piroxicam therapy. Medical records of dogs presented to the Purdue Veterinary Teaching Hospital between 2005 and 2015 were reviewed, and 137 dogs met the criteria for study inclusion. Toxic effects of piroxicam in these dogs were graded according to an established system. Multivariate logistic regression was used to estimate the extent to which certain factors affected the risk for AEs. Age [odds ratio (OR) 1.250, P = 0.009; 95% confidence interval (CI) 1.057-1.479] and concurrent use of gastroprotectant medications (OR 2.612, P = 0.025; 95% CI 1.127-6.056) significantly increased the risk for gastrointestinal AEs. The results of this study may help inform the risk versus benefit calculation for clinicians considering the use of piroxicam to treat dogs with cancer. © 2016 John Wiley & Sons Ltd.

Dose Effect of Rhenium (I)-diselenoether as Anticancer Drug in Resistant Breast Tumor-bearing Mice After Repeated Administrations.

PubMed

Collery, Philippe; Santoni, François; Ciccolini, Joseph; Tran, Thi Ngoc Nga; Mohsen, Ahmed; Desmaele, Didier

2016-11-01

Rhenium (I)-diselenoether has shown promising antiproliferative efficacy in both in vitro and in vivo models. However, the maximal tolerated dose and dose-effect relationships have not been fully addressed for this compound. Here, we evaluated the tolerance and efficacy of three dose-levels (namely 10, 40 and 100 mg/kg) intraperitoneally administered daily over 28 days in mice bearing the resistant MDA-MB231 breast cancer cell line. The upper dose was found to be toxic and was reduced to 60 mg/kg. The 10 mg/kg dose well tolerated, whereas 40 mg/kg was associated with 10% mortality (LD 10 ). Both 10 and 40 mg/kg dosing achieved a significantly similar regression of tumor growth compared with untreated animals. This study suggests that 10 mg/kg daily is the recommended dose for rhenium (I) diselenoether. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

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

Gouder, T.; Colmenares, C.

This report summarizes the experimental work carried out at the Lawrence Livermore National Laboratory on the electronic structure and reactivity of uranium thin films on Pd, Pt, Si, graphite, Cu, and Au substrates from 1990 to 1993. The U-Pd system was studied in the most detail because it was the first to be chosen right after the completion of the experimental equipment. We first studied and characterized clean U overlayers and the possible surface reactions between this metal and the substrates studied. We then subjected these systems to reactive conditions such as heating and adsorbing corrosive gases (O{sub 2}, CO,more » CO{sub 2}, and C{sub 2}H{sub 4}). Finally we investigated the diffusion of U metal and some of its compounds into the substrates. A new technique was developed, based on Auger Electron Spectroscopy, to follow in real time the diffusion of U overlayers into the substrate. The temperature of the sample is ramped linearly up to 900{degrees}C while following the Auger peak intensities of the two components for a given system. Diffusion rates are obtained by differentiating the measured intensity curves, then peaks result corresponding to diffusion processes with different activation energies. This technique bears a strong similarity to thermal desorption spectroscopy (TDS), where the sample is heated linearly and the rate of desorption is measured as a function of temperature and heating rate.« less

HYDROGEN CHLORIDE IN DIFFUSE INTERSTELLAR CLOUDS ALONG THE LINE OF SIGHT TO W31C (G10.6-0.4)

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

Monje, R. R.; Lis, D. C.; Phillips, T. G.

2013-04-10

We report the detection of hydrogen chloride, HCl, in diffuse molecular clouds on the line of sight toward the star-forming region W31C (G10.6-0.4). The J = 1-0 lines of the two stable HCl isotopologues, H{sup 35}Cl and H{sup 37}Cl, are observed using the 1b receiver of the Heterodyne Instrument for the Far-Infrared (HIFI) on board the Herschel Space Observatory. The HCl line is detected in absorption, over a wide range of velocities associated with diffuse clouds along the line of sight to W31C. The analysis of the absorption strength yields a total HCl column density of a few 10{sup 13}more » cm{sup -2}, implying that HCl accounts for {approx}0.6% of the total gas-phase chlorine, which exceeds the theoretical model predictions by a factor of {approx}6. This result is comparable to those obtained from the chemically related species H{sub 2}Cl{sup +} and HCl{sup +}, for which large column densities have also been reported on the same line of sight. The source of discrepancy between models and observations is still unknown; however, the detection of these Cl-bearing molecules provides key constraints for the chlorine chemistry in the diffuse gas.« less

Fast and Accurate Poisson Denoising With Trainable Nonlinear Diffusion.

PubMed

Feng, Wensen; Qiao, Peng; Chen, Yunjin; Wensen Feng; Peng Qiao; Yunjin Chen; Feng, Wensen; Chen, Yunjin; Qiao, Peng

2018-06-01

The degradation of the acquired signal by Poisson noise is a common problem for various imaging applications, such as medical imaging, night vision, and microscopy. Up to now, many state-of-the-art Poisson denoising techniques mainly concentrate on achieving utmost performance, with little consideration for the computation efficiency. Therefore, in this paper we aim to propose an efficient Poisson denoising model with both high computational efficiency and recovery quality. To this end, we exploit the newly developed trainable nonlinear reaction diffusion (TNRD) model which has proven an extremely fast image restoration approach with performance surpassing recent state-of-the-arts. However, the straightforward direct gradient descent employed in the original TNRD-based denoising task is not applicable in this paper. To solve this problem, we resort to the proximal gradient descent method. We retrain the model parameters, including the linear filters and influence functions by taking into account the Poisson noise statistics, and end up with a well-trained nonlinear diffusion model specialized for Poisson denoising. The trained model provides strongly competitive results against state-of-the-art approaches, meanwhile bearing the properties of simple structure and high efficiency. Furthermore, our proposed model comes along with an additional advantage, that the diffusion process is well-suited for parallel computation on graphics processing units (GPUs). For images of size , our GPU implementation takes less than 0.1 s to produce state-of-the-art Poisson denoising performance.

Transmucosal Delivery of Nicotine in Combination with Tincture of Benzoin Inhibits Apoptosis.

PubMed

Battaglia, Alex; Nguyen, Thanh

2017-12-01

The aim of this study was to test the hypothesis that tincture of benzoin (TOB) facilitates immediate transmucosal nicotine absorption while simultaneously promoting a safe and sustained delivery of the nicotine. In combination with TOB, nicotine toxicity and diffusion across human mucosal cells were measured using a 3-D human mucosal tissue model. Nicotine was delivered 2.1 times more quickly in combination with TOB than in combination with saline (p < 0.05). Despite the increased diffusion, nicotine in combination with TOB significantly increased mucosal cell survival (p < 0.05) by reducing the release of mitochondrial cytochrome c into the cytoplasm when compared with nicotine without TOB. The average percentage distribution of cytochrome c in the cytosolic fraction over time of nicotine + 79% ethyl alcohol (ETOH) versus nicotine plus TOB (79% ETOH) was significantly different over 120 min (60.0 ± 29.9% cytosol, 16.1 ± 9.4% cytosol, p = 0.03). Related to the reduction of cytochrome c release into the cytoplasm, TOB suppressed caspase-3 and -9 activity, thereby preventing intrinsic apoptosis and providing cytoprotection of the mucosal cells (ETOH + nicotine vs ETOH + nicotine + TOB: p = 0.008 for caspase 3, p < 0.001 for caspase 9). Two hours of TOB (17-24% benzoin, 79% ETOH) plus nicotine promotes diffusion of nicotine across human mucosal cells and simultaneously prevents human mucosal cell toxicity by inhibiting cytochrome c release into the cytosol, thereby preventing caspase 3 and 9 activity and subsequent intrinsic apoptosis.

Protection against methotrexate toxicity by a soybean protein- and omega-3 fatty acid-containing diet: comparative study with a casein-containing diet.

PubMed

Mitsugi, Kenji; Nakamura, Tsuyoshi; Kashiwabara, Norio; Ariyama, Hiroshi; Tanaka, Risa; Baba, Eishi; Nakamura, Minoru; Harada, Mine; Nakano, Shuji

2004-07-01

Effects of two clinically used liquid diets on toxicity and antitumor activity of methotrexate (MTX) were investigated in Sprague-Dawley (SD) rats and tumor-bearing mice, respectively. Diets tested were commercially available formulas enriched either with soybean and omega-3 fatty acids or with casein. The soybean-containing diet offered significant protection against MTX toxicity in rats compared with the casein-containing diet, completely alleviating MTX-induced anorexia, diarrhea, and weight loss, when ingested as the sole diet and fed 7 days prior to and 7 days following intraperitoneal MTX injection. As a result, 90% of rats were alive on soybean-containing diet while all rats were dead on casein-containing diet. Histologic examination of the small intestine of MTX-treated rats revealed that the soybean-containing diet significantly prevented loss of mucosal villus tips compared to the casein-containing diet. Pharmocokinetic examination indicated that plasma MTX concentrations were similar for rats in the two diet-defined groups. No significant differences were observed between diets in survival of mice injected with L1210 mouse leukemia cells and subsequently with MTX. Thus the soybean-containing diet appeared to be superior to the casein-containing diet in preventing gastrointestinal toxicity while preserving antitumor activity. A soybean diet enriched in omega-3 fatty acids may be a useful adjunct to MTX treatment of human cancers.

Cadmium and Zn availability as affected by pH manipulation and its assessment by soil extraction, DGT and indicator plants.

PubMed

Muhammad, Iqbal; Puschenreiter, Markus; Wenzel, Walter W

2012-02-01

Manipulation of soil pH by soil additives and / or rhizosphere processes may enhance the efficiency of metal phytoextraction. Here we report on the effect of nitric acid additions to four polluted soils on Cd and Zn concentrations in soil solution (C(soln)) and 0.005M Ca(NO(3))(2) extracts, and related changes in the diffusive fluxes and resupply of the metals as assessed by diffusive gradients in thin films (DGT). The responses of these chemical indicators of bioavailability were compared to metal uptake in two indicator plant species, common dandelion (Taraxacum officinale F.H. Wigg) and narrow leaf plantain (Plantago lanceolata L.) grown for 75days in a pot experiment. Lowering soil pH increased C(soln), the 0.005M Ca(NO(3))(2)-soluble fractions and the DGT-measured Cd and Zn concentrations (C(DGT)) in the experimental soils. This was associated with enhanced uptake of Cd and Zn on soils acidified to pH 4.5 whereas plants did not survive at pH 3.5. Toxicity along with decreased kinetics of metal resupply (calculated by the 2D DIFS model) in the strong acidification treatment suggests that moderate acidification is more appropriate to enhance the phytoextraction process. Each of the chemical indicators of bioavailability predicted well (R(2)>0.70) the Cd and Zn concentrations in plantain shoots but due to metal toxicity not for dandelion. Concentration factors, i.e. the ratio between metal concentrations in shoots and in soil solution (CF) indicate that Cd and Zn uptake in plantain was not limited by diffusion which may explain that DGT did not perform better than C(soln). However, DGT is expected to predict plant uptake better in diffusion-limited conditions such as in the rhizosphere of metal-accumulating phytoextraction crops. Copyright © 2011 Elsevier B.V. All rights reserved.

In vitro biopharmaceutical evaluation of ciprofloxacin/metal cation complexes for pulmonary administration.

PubMed

Brillault, J; Tewes, F; Couet, W; Olivier, J C

2017-01-15

Pulmonary delivery of fluoroquinolones (FQs) is an interesting approach to treat lung infections as it may lead to high local concentrations while minimizing systemic exposure. However, FQs have a rapid diffusion through the lung epithelium giving the pulmonary route no advantage compared to the oral route. Interactions between FQs and metal cations form complexes which limit the diffusion through the epithelial barrier and would reduce the absorption of FQs and maintain high concentrations in the lung. The effects of this complexation depend on the FQ and the metal cations and optimum partners should be selected through in vitro experiments prior to aerosol drug formulation. In this study, CIP was chosen as a representative FQ and 5 cations (Ca 2+ , Mg 2+ , Zn 2+ , Al 3+ , Cu 2+ ) were selected to study the complexation and its effects on permeability, antimicrobial efficacy and cell toxicity. The results showed that the apparent association constants between CIP and cations ranked with the descending order: Cu 2+ >Al 3+ >Zn 2+ >Mg 2+ >Ca 2+ . When a target of 80% complexation was reached with the adequate concentrations of cations, the CIP permeability through the Calu-3 lung epithelial cells was decreased of 50%. Toxicity of the CIP on the Calu-3 cells, with an EC50 evaluated at 7μM, was not significantly affected by the presence of the cations. The minimum inhibitory concentration of CIP for Pseudomonas aeruginosa was not affected or slightly increased in the range of cation concentrations tested, except for Mg 2+ . In conclusion, permeability was the main parameter that was affected by the metal cation complexation while cell toxicity and antimicrobial activity were not or slightly modified. Cu 2+ , with the highest apparent constant of association and with no effect on cell toxicity and antimicrobial activity of the CIP, appeared as a promising cation for the development of a controlled-permeability formulation of CIP for lung treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Molecular dimensions and surface diffusion assisted mechanically robust slippery perfluoropolyether impregnated mesoporous alumina interfaces

NASA Astrophysics Data System (ADS)

Rowthu, Sriharitha; Balic, Edin E.; Hoffmann, Patrik

2017-12-01

Accomplishing mechanically robust omniphobic surfaces is a long-existing challenge, and can potentially find applications in bioengineering, tribology and paint industries. Slippery liquid impregnated mesoporous α-Al2O3 interfaces are achieved with water, alkanes, water based and oil based high viscosity acrylic paints. Incredibly high abrasion-resistance (wear coefficients ≤10-8 mm3 N-1 m-1) and ultra-low friction coefficients (≥0.025) are attained, attributing to the hard alumina matrix and continuous replenishment of perfluoropolyether aided by capillarity and surface diffusion processes. A variety of impregnating liquids employed suggest that large molecules, faster surface diffusion and lowest evaporation rate generate the rare combination of high wear-resistance and omniphobicity. It is noteworthy that these novel liquid impregnated Al2O3 composites exhibit outstanding load bearing capacity up to 350 MPa; three orders of magnitude higher than achievable by the state of the art omniphobic surfaces. Further, our developed thermodynamic calculations suggest that the relative thermodynamic stability of liquid impregnated composites is linearly proportional to the spreading coefficient (S) of the impregnating liquid with the matrix material and is an important tool for the selection of an appropriate matrix material for a given liquid.

Increased working memory related fMRI signal in children following Tick Borne Encephalitis.

PubMed

Henrik, Ullman; Åsa, Fowler; Ronny, Wickström

2016-01-01

Tick Borne Encephalitis (TBE) is a viral infection in the central nervous system endemic in Europe and Asia. While pediatric infection may carry a lower risk for serious neurological sequelae compared to adults, a large proportion of children experience long term cognitive problems, most markedly decreased working memory capacity. We explored whether task related functional magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) could reveal a biological correlate of status-post TBE in children. We examined 11 serologically verified pediatric TBE patients with central nervous system involvement with 55 healthy controls with working memory tests and MRI. The TBE patients showed a prominent deficit in working memory capacity and an increased task related functional MRI signal in working memory related cortical areas during a spatial working memory task performed without sedation. No diffusion differences could be found with DTI, in line with the reported paucity of anatomical abnormalities. This study is the first to demonstrate functional MRI abnormalities in TBE patients that bears similarity to other patient groups with diffuse neuronal damage. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Changes in Water Mobility Measured by Diffusion MRI Predict Response of Metastatic Breast Cancer to Chemotherapy

PubMed Central

Theilmann, Rebecca J; Borders, Rebecca; Trouard, Theodore P; Xia, Guowei; Outwater, Eric; Ranger-Moore, James; Gillies, Robert J; Stopeck, Alison

2004-01-01

Abstract A goal of oncology is the individualization of patient care to optimize therapeutic responses and minimize toxicities. Achieving this will require noninvasive, quantifiable, and early markers of tumor response. Preclinical data from xenografted tumors using a variety of antitumor therapies have shown that magnetic resonance imaging (MRI)-measured mobility of tissue water (apparent diffusion coefficient of water, or ADCw) is a biomarker presaging cell death in the tumor. This communication tests the hypothesis that changes in water mobility will quantitatively presage tumor responses in patients with metastatic liver lesions from breast cancer. A total of 13 patients with metastatic breast cancer and 60measurable liver lesionsweremonitored by diffusion MRI after initiation of new courses of chemotherapy. MR images were obtained prior to, and at 4, 11, and 39 days following the initiation of therapy for determination of volumes and ADCw values. The data indicate that diffusion MRI can predict response by 4 or 11 days after commencement of therapy, depending on the analytic method. The highest concordance was observed in tumor lesions that were less than 8 cm3 in volume at presentation. These results suggest that diffusion MRI can be useful to predict the response of liver metastases to effective chemotherapy. PMID:15720810

Fatal streptococcal toxic shock syndrome from an intrauterine device.

PubMed

Cho, Elizabeth E; Fernando, Dinali

2013-04-01

The occurrence of toxic shock syndrome from an intrauterine device (IUD) is very rare. To raise awareness of the risk of toxic shock syndrome caused by an IUD, to educate others about when to suspect this complication, and to provide treatment recommendations. A 49-year-old woman presented to the Emergency Department in septic shock after complaining of 5 days of nausea, vomiting, and diarrhea. Physical examination findings included a diffusely tender and rigid abdomen with free fluid on bedside sonogram. She was found, on computed tomography of her abdomen and pelvis, to have an IUD with moderate ascites. The IUD was removed, and both her IUD and her blood cultures grew out group A Streptococcus. Despite aggressive medical management, which included multiple vasopressors and broad-spectrum antibiotics, she died from group A streptococcal sepsis, with the IUD as her most likely source. Her clinical presentation and laboratory findings meet the Centers for Disease Control and Prevention diagnostic criteria for streptococcal toxic shock syndrome. Her diagnosis was confirmed by autopsy. IUDs should be considered as a possible source of infection in patients with an IUD who present with symptoms consistent with toxic shock syndrome. These patients need to be aggressively managed with early surgical intervention. Copyright © 2013. Published by Elsevier Inc.

Properties and applications of zeolites.

PubMed

Rhodes, Christopher J

2010-01-01

Zeolites are aluminosilicate solids bearing a negatively charged honeycomb framework of micropores into which molecules may be adsorbed for environmental decontamination, and to catalyse chemical reactions. They are central to green-chemistry since the necessity for organic solvents is minimised. Proton-exchanged (H) zeolites are extensively employed in the petrochemical industry for cracking crude oil fractions into fuels and chemical feedstocks for other industrial processes. Due to their ability to perform cation-exchange, in which the cations that are originally present to counterbalance the framework negative charge may be exchanged out of the zeolite by cations present in aqueous solution, zeolites are useful as industrial water-softeners, in the removal of radioactive Cs+ and Sr2+ cations from liquid nuclear waste and in the removal of toxic heavy metal cations from groundwaters and run-off waters. Surfactant-modified zeolites (SMZ) find particular application in the co-removal of both toxic anions and organic pollutants. Toxic anions such as arsenite, arsenate, chromate, cyanide and radioactive iodide can also be removed by adsorption into zeolites that have been previously loaded with co-precipitating metal cations such as Ag+ and Pb2+ which form practically insoluble complexes that are contained within the zeolite matrix.

Specific Inhibition of Bacterial β-Glucuronidase by Pyrazolo[4,3-c]quinoline Derivatives via a pH-Dependent Manner To Suppress Chemotherapy-Induced Intestinal Toxicity.

PubMed

Cheng, Kai-Wen; Tseng, Chih-Hua; Yang, Chia-Ning; Tzeng, Cherng-Chyi; Cheng, Ta-Chun; Leu, Yu-Lin; Chuang, Yu-Chung; Wang, Jaw-Yuan; Lu, Yun-Chi; Chen, Yeh-Long; Cheng, Tian-Lu

2017-11-22

The direct inhibition of bacterial β-glucuronidase (βG) activity is expected to reduce the reactivation of glucuronide-conjugated drugs in the intestine, thereby reducing drug toxicity. In this study, we report on the effects of pyrazolo[4,3-c]quinolines acting as a new class of bacterial βG-specific inhibitors in a pH-dependent manner. Refinement of this chemotype for establishing structure-activity relationship resulted in the identification of potential leads. Notably, the oral administration of 3-amino-4-(4-fluorophenylamino)-1H-pyrazolo[4,3-c]quinoline (42) combined with chemotherapeutic CPT-11 treatment prevented CPT-11-induced serious diarrhea while maintaining the antitumor efficacy in tumor-bearing mice. Importantly, the inhibitory effects of 42 to E. coli βG was reduced as the pH decreased due to the various surface charges of the active pocket of the enzyme, which may make their combination more favorable at neutral pH. These results demonstrate novel insights into the potent bacterial βG-specific inhibitor that would allow this inhibitor to be used for the purpose of reducing drug toxicity.

Buzz Juice: Neurological sequelae of synthetic cannabinoids.

PubMed

Kak, Manisha; Mikhail, Fadi; Yano, Sho T; Guan, Rui; Lukas, Rimas V

2017-03-01

The use of synthetic cannabinoids is becoming more widespread. Familiarity with the potential toxicities associated with these agents will grow in importance. We present a case of a woman who developed onset of confusion, visual hallucinations, and ataxia after vaporizing synthetic cannabinoids. MRI imaging demonstrated restricted diffusion and increased T2/FLAIR signal in the corpus callosum and cerebellar peduncles. Copyright © 2016 Elsevier Ltd. All rights reserved.

Time domain diffuse optical spectroscopy: In vivo quantification of collagen in breast tissue

NASA Astrophysics Data System (ADS)

Taroni, Paola; Pifferi, Antonio; Quarto, Giovanna; Farina, Andrea; Ieva, Francesca; Paganoni, Anna Maria; Abbate, Francesca; Cassano, Enrico; Cubeddu, Rinaldo

2015-05-01

Time-resolved diffuse optical spectroscopy provides non-invasively the optical characterization of highly diffusive media, such as biological tissues. Light pulses are injected into the tissue and the effects of light propagation on re-emitted pulses are interpreted with the diffusion theory to assess simultaneously tissue absorption and reduced scattering coefficients. Performing spectral measurements, information on tissue composition and structure is derived applying the Beer law to the measured absorption and an empiric approximation to Mie theory to the reduced scattering. The absorption properties of collagen powder were preliminarily measured in the range of 600-1100 nm using a laboratory set-up for broadband time-resolved diffuse optical spectroscopy. Optical projection images were subsequently acquired in compressed breast geometry on 218 subjects, either healthy or bearing breast lesions, using a portable instrument for optical mammography that operates at 7 wavelengths selected in the range 635-1060 nm. For all subjects, tissue composition was estimated in terms of oxy- and deoxy-hemoglobin, water, lipids, and collagen. Information on tissue microscopic structure was also derived. Good correlation was obtained between mammographic breast density (a strong risk factor for breast cancer) and an optical index based on collagen content and scattering power (that accounts mostly for tissue collagen). Logistic regression applied to all optically derived parameters showed that subjects at high risk for developing breast cancer for their high breast density can effectively be identified based on collagen content and scattering parameters. Tissue composition assessed in breast lesions with a perturbative approach indicated that collagen and hemoglobin content are significantly higher in malignant lesions than in benign ones.

Silver nanoparticles induce developmental stage-specific embryonic phenotypes in zebrafish

NASA Astrophysics Data System (ADS)

Lee, Kerry J.; Browning, Lauren M.; Nallathamby, Prakash D.; Osgood, Christopher J.; Xu, Xiao-Hong Nancy

2013-11-01

Much is anticipated from the development and deployment of nanomaterials in biological organisms, but concerns remain regarding their biocompatibility and target specificity. Here we report our study of the transport, biocompatibility and toxicity of purified and stable silver nanoparticles (Ag NPs, 13.1 +/- 2.5 nm in diameter) upon the specific developmental stages of zebrafish embryos using single NP plasmonic spectroscopy. We find that single Ag NPs passively diffuse into five different developmental stages of embryos (cleavage, early-gastrula, early-segmentation, late-segmentation, and hatching stages), showing stage-independent diffusion modes and diffusion coefficients. Notably, the Ag NPs induce distinctive stage and dose-dependent phenotypes and nanotoxicity, upon their acute exposure to the Ag NPs (0-0.7 nM) for only 2 h. The late-segmentation embryos are most sensitive to the NPs with the lowest critical concentration (CNP,c << 0.02 nM) and highest percentages of cardiac abnormalities, followed by early-segmentation embryos (CNP,c < 0.02 nM), suggesting that disruption of cell differentiation by the NPs causes the most toxic effects on embryonic development. The cleavage-stage embryos treated with the NPs develop into a wide variety of phenotypes (abnormal finfold, tail/spinal cord flexure, cardiac malformation/edema, yolk sac edema, and acephaly). These organ structures are not yet developed in cleavage-stage embryos, suggesting that the earliest determinative events to create these structures are ongoing, and disrupted by NPs, which leads to the downstream effects. In contrast, the hatching embryos are most resistant to the Ag NPs, and majority of embryos (94%) develop normally, and none of them develop abnormally. Interestingly, early-gastrula embryos are less sensitive to the NPs than cleavage and segmentation stage embryos, and do not develop abnormally. These important findings suggest that the Ag NPs are not simple poisons, and they can target specific pathways in development, and potentially enable target specific study and therapy for early embryonic development.Much is anticipated from the development and deployment of nanomaterials in biological organisms, but concerns remain regarding their biocompatibility and target specificity. Here we report our study of the transport, biocompatibility and toxicity of purified and stable silver nanoparticles (Ag NPs, 13.1 +/- 2.5 nm in diameter) upon the specific developmental stages of zebrafish embryos using single NP plasmonic spectroscopy. We find that single Ag NPs passively diffuse into five different developmental stages of embryos (cleavage, early-gastrula, early-segmentation, late-segmentation, and hatching stages), showing stage-independent diffusion modes and diffusion coefficients. Notably, the Ag NPs induce distinctive stage and dose-dependent phenotypes and nanotoxicity, upon their acute exposure to the Ag NPs (0-0.7 nM) for only 2 h. The late-segmentation embryos are most sensitive to the NPs with the lowest critical concentration (CNP,c << 0.02 nM) and highest percentages of cardiac abnormalities, followed by early-segmentation embryos (CNP,c < 0.02 nM), suggesting that disruption of cell differentiation by the NPs causes the most toxic effects on embryonic development. The cleavage-stage embryos treated with the NPs develop into a wide variety of phenotypes (abnormal finfold, tail/spinal cord flexure, cardiac malformation/edema, yolk sac edema, and acephaly). These organ structures are not yet developed in cleavage-stage embryos, suggesting that the earliest determinative events to create these structures are ongoing, and disrupted by NPs, which leads to the downstream effects. In contrast, the hatching embryos are most resistant to the Ag NPs, and majority of embryos (94%) develop normally, and none of them develop abnormally. Interestingly, early-gastrula embryos are less sensitive to the NPs than cleavage and segmentation stage embryos, and do not develop abnormally. These important findings suggest that the Ag NPs are not simple poisons, and they can target specific pathways in development, and potentially enable target specific study and therapy for early embryonic development. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr03210h

Geogenic organic contaminants in the low-rank coal-bearing Carrizo-Wilcox aquifer of East Texas, USA

USGS Publications Warehouse

Chakraborty, Jayeeta; Varonka, Matthew S.; Orem, William H.; Finkelman, Robert B.; Manton, William

2017-01-01

The organic composition of groundwater along the Carrizo-Wilcox aquifer in East Texas (USA), sampled from rural wells in May and September 2015, was examined as part of a larger study of the potential health and environmental effects of organic compounds derived from low-rank coals. The quality of water from the low-rank coal-bearing Carrizo-Wilcox aquifer is a potential environmental concern and no detailed studies of the organic compounds in this aquifer have been published. Organic compounds identified in the water samples included: aliphatics and their fatty acid derivatives, phenols, biphenyls, N-, O-, and S-containing heterocyclic compounds, polycyclic aromatic hydrocarbons (PAHs), aromatic amines, and phthalates. Many of the identified organic compounds (aliphatics, phenols, heterocyclic compounds, PAHs) are geogenic and originated from groundwater leaching of young and unmetamorphosed low-rank coals. Estimated concentrations of individual compounds ranged from about 3.9 to 0.01 μg/L. In many rural areas in East Texas, coal strata provide aquifers for drinking water wells. Organic compounds observed in groundwater are likely to be present in drinking water supplied from wells that penetrate the coal. Some of the organic compounds identified in the water samples are potentially toxic to humans, but at the estimated levels in these samples, the compounds are unlikely to cause acute health problems. The human health effects of low-level chronic exposure to coal-derived organic compounds in drinking water in East Texas are currently unknown, and continuing studies will evaluate possible toxicity.

On N. Park's Analytical solution for steady state density- and mixing regime—dependent solute transport in a vertical soil column

NASA Astrophysics Data System (ADS)

Thiele, Michael

1998-04-01

Recently, Park [1996] presented an analytical solution for stationary one-dimensional solute transport in a variable-density fluid flow through a vertical soil column. He used the widespread Bear-Scheidegger dispersion model describing solute mixing as a sum of molecular diffusion and velocity-proportional mechanical dispersion effects. His closed-form implicit concentration and pressure distributions thus allow for a discussion of the combined impact of molecular diffusion and mechanical dispersion in a variable-density environment. Whereas Park only considered the example of vanishing molecular diffusion in detail, both phenomena are taken into account simultaneously in the present study in order to elucidate their different influences on concentration distribution characteristics. The boundary value problem dealt with herein is based on an upward inflow of high-density fluid of constant solute concentration and corresponding outflow of a lower constant concentration fluid at the upper end of the column when dispersivity does not change along the flow path. The thickness of the transition zone between the two fluids appeared to strongly depend on the prevailing share of the molecular diffusion and mechanical dispersion mechanisms. The latter can be characterized by a molecular Peclet number Pe, which here is defined as the ratio of the column outflow velocity multiplied by a characteristic pore size and the molecular diffusion coefficient. For very small values of Pe, when molecular diffusion represents the exclusive mixing process, density differences have no impact on transition zone thicknesses. A relative density-;dependent thickness increases with flow velocities (increasing Pe values) very rapidly compared to the density-independent case, and after having passed a maximum decreases asymptotically to a constant value for the large Peclet number limit when mechanical dispersion is the only mixing mechanism. Hence the special transport problem analyzed gives further evidence for the importance of simultaneously considering molecular diffusion and mechanical dispersion in gravity-affected solute transport in porous media.

Extending FEAST-METAL for analysis of low content minor actinide bearing and zirconium rich metallic fuels for sodium fast reactors

NASA Astrophysics Data System (ADS)

Karahan, Aydın

2011-07-01

Computational models in FEAST-METAL fuel behaviour code have been upgraded to simulate minor actinide bearing zirconium rich metallic fuels for use in sodium fast reactors. Increasing the zirconium content to 20-40 wt.% causes significant changes in fuel slug microstructure affecting thermal, mechanical, chemical, and fission gas behaviour. Inclusion of zirconium rich phase reduces the fission gas swelling rate significantly in early irradiation. Above the threshold fission gas swelling, formation of micro-cracks, and open pores increase material compliancy enhance diffusivity, leading to rapid fuel gas swelling, interconnected porosity development and release of the fission gases and helium. Production and release of helium was modelled empirically as a function of americium content and fission gas production, consistent with previous Idaho National Laboratory studies. Predicted fuel constituent redistribution is much smaller compared to typical U-Pu-10Zr fuel operated at EBR-II. Material properties such as fuel thermal conductivity, modulus of elasticity, and thermal expansion coefficient have been approximated using the available database. Creep rate and fission gas diffusivity of high zirconium fuel is lowered by an order of magnitude with respect to the reference low zirconium fuel based on limited database and in order to match experimental observations. The new code is benchmarked against the AFC-1F fuel assembly post irradiation examination results. Satisfactory match was obtained for fission gas release and swelling behaviour. Finally, the study considers a comparison of fuel behaviour between high zirconium content minor actinide bearing fuel and typical U-15Pu-6Zr fuel pins with 75% smear density. The new fuel has much higher fissile content, allowing for operating at lower neutron flux level compared to fuel with lower fissile density. This feature allows the designer to reach a much higher burnup before reaching the cladding dose limit. On the other hand, in order to accommodate solid fission product swelling and to control fuel clad mechanical interaction of the stiffer fuel, the fuel smear density is reduced to 70%. In addition, plenum height is increased to accommodate for fission gases.

Comparative efficacy of 177Lu and 90Y for Anti-CD20 Pretargeted Radioimmunotherapy in Murine Lymphoma Xenograft Models

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

Frost, Sofia H. L.; Frayo, Shani L.; Miller, Brian W.

Purpose Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 ( 90Y) and lutetium-177 ( 177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potentialmore » of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice. Methods Parallel experiments evaluating the biodistribution, imaging, dosimetry, therapeutic efficacy, and toxicity were performed in female athymic nude mice bearing either Ramos (Burkitt lymphoma) or Granta (mantle cell lymphoma) xenografts, utilizing an anti-CD20 antibodystreptavidin conjugate (1F5-SA) and an 90Y- or 177Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin second step reagent. Results The two radionuclides displayed comparable biodistributions in tumors and normal organs; however, the absorbed radiation dose delivered to tumor was more than twice as high for 90Y (1.3 Gy/MBq) as for 177Lu (0.6 Gy/MBq). More importantly, therapy with 90Y-DOTAbiotin was dramatically more effective than with 177Lu-DOTA-biotin, with 100% of Ramos xenograft-bearing mice cured with 37 MBq 90Y, whereas 0% were cured using identical amounts of 177Lu-DOTA-biotin. Similar results were observed in mice bearing Granta xenografts, with 80% of the mice cured with 90Y-PRIT and 0% cured with 177Lu-PRIT. Toxicities were comparable with both isotopes. Conclusion 90Y was therapeutically superior to 177Lu for streptavidin-biotin PRIT approaches in these human lymphoma xenograft models.« less

Studying microfungi-mineral interactions in sulphide-bearing waste-rock dumps: a 7 years survey in the Libiola mine, North-Eastern Italy

NASA Astrophysics Data System (ADS)

Marescotti, P.; Cecchi, G.; Di Piazza, S.; Lucchetti, G.; Zotti, M.

2015-12-01

Sulphide-bearing waste-rock dumps represent complex geological systems characterised by high percentages of low-grade mineralisations and non-valuable sulphides (such as pyrite and pyrrhotite). The sulphide oxidation triggers acid mine drainage (AMD) processes and the release of several metals of environmental concern. The severe physicochemical properties of these metal-contaminated environments tend to inhibit soil forming processes and represent an important stress factor for the biotic communities by exerting a strong selective pressure. Some macro- and micro-fungi are pioneer and extremophile organisms, which may survive and tolerate high concentrations of toxic metals in contaminated environments. Many studies show the fungal capability to bioaccumulate, biosorb, and store in their cells a high concentration of ecotoxic metals. A 7 years multidisciplinary survey was carried out in the Libiola sulphide mine. The results evidenced that the waste rock dumps of the area are characterized by an extremely poor flora and a specific mycobiota, due to the soil acidity, high concentration of trace metals, and unavailability or paucity of nutrients and organic matter. Our studies allowed the complete mineralogical, geochemical, and mycological characterization of one of the biggest dumps of the mine. 30 microfungal vital strains were isolated in pure cultures and studied with molecular and morphological approach, for their identification. The results allowed the isolation of some rare and important extremophilic species. Penicillium was the most recurrent genus, together with Trichoderma and Cladosporium. In particular, Penicillium glandicola is a rare species previously isolated from cave or arid environments, whereas P. brevicompactum is one of the most important fungi for metal corrosion. Hence, some bioaccumulation tests allowed to select a Trichoderma harzianum strain efficient to uptake Cu and Ag from pyrite-bearing soils, highlighting its central role in fungal remediation protocol. Further studies are in progress to investigate the potential interactions between microfungi and sulphides from the Libiola mine soils and to evaluate the fungal role in the biomineralisation and deactivation/mobilisation of toxic metals.

Comparative efficacy of 177Lu and 90Y for Anti-CD20 Pretargeted Radioimmunotherapy in Murine Lymphoma Xenograft Models

DOE PAGES

Frost, Sofia H. L.; Frayo, Shani L.; Miller, Brian W.; ...

2015-03-18

Purpose Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 ( 90Y) and lutetium-177 ( 177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potentialmore » of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice. Methods Parallel experiments evaluating the biodistribution, imaging, dosimetry, therapeutic efficacy, and toxicity were performed in female athymic nude mice bearing either Ramos (Burkitt lymphoma) or Granta (mantle cell lymphoma) xenografts, utilizing an anti-CD20 antibodystreptavidin conjugate (1F5-SA) and an 90Y- or 177Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin second step reagent. Results The two radionuclides displayed comparable biodistributions in tumors and normal organs; however, the absorbed radiation dose delivered to tumor was more than twice as high for 90Y (1.3 Gy/MBq) as for 177Lu (0.6 Gy/MBq). More importantly, therapy with 90Y-DOTAbiotin was dramatically more effective than with 177Lu-DOTA-biotin, with 100% of Ramos xenograft-bearing mice cured with 37 MBq 90Y, whereas 0% were cured using identical amounts of 177Lu-DOTA-biotin. Similar results were observed in mice bearing Granta xenografts, with 80% of the mice cured with 90Y-PRIT and 0% cured with 177Lu-PRIT. Toxicities were comparable with both isotopes. Conclusion 90Y was therapeutically superior to 177Lu for streptavidin-biotin PRIT approaches in these human lymphoma xenograft models.« less

The Role of Intestinal Microbiota in Development of Irinotecan Toxicity and in Toxicity Reduction through Dietary Fibres in Rats

PubMed Central

Lin, Xiaoxi B.; Farhangfar, Arazm; Valcheva, Rosica; Sawyer, Michael B.; Dieleman, Levinus; Schieber, Andreas; Gänzle, Michael G.; Baracos, Vickie

2014-01-01

CPT-11 is a drug used as chemotherapy for colorectal cancer. CPT-11 causes toxic side-effects in patients. CPT-11 toxicity has been attributed to the activity of intestinal microbiota, however, intestinal microbiota may also have protective effects in CP!-11 chemotherapy. This study aimed to elucidate mechanisms through which microbiota and dietary fibres could modify host health. Rats bearing a Ward colon carcinoma were treated with a two-cycle CPT-11/5-fluorouracil therapy recapitulating clinical therapy of colorectal cancer. Animals were fed with a semi-purified diet or a semi-purified diet was supplemented with non-digestible carbohydrates (isomalto-oligosaccharides, resistant starch, fructo-oligosaccharides, or inulin) in 3 independent experiments. Changes in intestinal microbiota, bacteria translocating to mesenteric lymphnodes, cecal GUD activity, and cecal SCFA production, and the intestinal concentration of CPT-11 and its metabolites were analysed. Non-digestible carbohydrates significantly influenced feed intake, body weight and other indicators of animal health. The identification of translocating bacteria and their quantification in cecal microbiota indicated that overgrowth of the intestine by opportunistic pathogens was not a major contributor to CPT-11 toxicity. Remarkably, fecal GUD activity positively correlated to body weight and feed intake but negatively correlated to cecal SN-38 concentrations and IL1-β. The reduction in CPT-11 toxicity by non-digestible carbohydrates did not correlate to stimulation of specific bacterial taxa. However, cecal butyrate concentrations and feed intake were highly correlated. The protective role of intestinal butyrate production was substantiated by a positive correlation of the host expression of MCT1 (monocarboxylate transporter 1) with body weight as well as a positive correlation of the abundance of bacterial butyryl-CoA gene with cecal butyrate concentrations. These correlations support the interpretation that the influence of dietary fibre on CPT-11 toxicity is partially mediated by an increased cecal production of butyrate. PMID:24454707

Sodium selenosulfate at an innocuous dose markedly prevents cisplatin-induced gastrointestinal toxicity

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

Li, Jun; Sun, Kang; Ni, Lijuan

Our previous studies in mice revealed that two weeks short-term toxicity of sodium selenosulfate was significantly lower than that of sodium selenite, but selenium repletion efficacy of both compounds was equivalent. In addition, we showed that sodium selenosulfate reduced nephrotoxicity of cisplatin (CDDP) without compromising its anticancer activity, thus leading to a dramatic increase of cancer cure rate from 25% to 75%. Hydration has been used in clinical practice to reduce CDDP-induced nephrotoxicity, but it cannot mitigate CDDP-induced gastrointestinal toxicity. The present work investigated whether sodium selenosulfate is a potential preventive agent for the gastrointestinal toxicity. In tumor-bearing mice, sodiummore » selenosulfate was administered at a dose of 9.5 μmol/kg daily for 11 days, CDDP alone resulted in diarrhea by 88% on day 12, whereas the co-administration of CDDP and sodium selenosulfate dramatically reduced diarrhea to 6% (p < 0.0001). Such a prominent protective effect promoted us to evaluate the safety potential of long-term sodium selenosulfate application. Mice were administered with sodium selenosulfate or sodium selenite for 55 days at the doses of 12.7 and 19 μmol/kg. The low-dose sodium selenite caused growth suppression and hepatotoxicity which were aggravated by the high-dose, leading to 40% mortality rate, but no toxic symptoms were observed in the two sodium selenosulfate groups. Altogether these results clearly show that sodium selenosulfate at an innocuous dose can markedly prevent CDDP-induced gastrointestinal toxicity. -- Highlights: ►Cisplatin resulted in diarrhea in mice by 88%. ►i.p. selenosulfate at 9.5 μmol/kg daily for 11 days reduced diarrhea to 6%. ►i.p. selenosulfate at 19 μmol/kg daily for 55 days was not toxic. ►i.p. selenite at 19 μmol/kg daily for 55 days was lethal. ►Innocuous dose of selenosulfate greatly prevents cisplatin-induced diarrhea.« less

Early detection of response to radiation therapy in patients with brain malignancies using conventional and high b-value diffusion-weighted magnetic resonance imaging.

PubMed

Mardor, Yael; Pfeffer, Raphael; Spiegelmann, Roberto; Roth, Yiftach; Maier, Stephan E; Nissim, Ouzi; Berger, Raanan; Glicksman, Ami; Baram, Jacob; Orenstein, Arie; Cohen, Jack S; Tichler, Thomas

2003-03-15

To study the feasibility of using diffusion-weighted magnetic resonance imaging (DWMRI), which is sensitive to the diffusion of water molecules in tissues, for detection of early tumor response to radiation therapy; and to evaluate the additional information obtained from high DWMRI, which is more sensitive to low-mobility water molecules (such as intracellular or bound water), in increasing the sensitivity to response. Standard MRI and DWMRI were acquired before and at regular intervals after initiating radiation therapy for 10 malignant brain lesions in eight patients. One week posttherapy, three of six responding lesions showed an increase in the conventional DWMRI parameters. Another three responding lesions showed no change. Four nonresponding lesions showed a decrease or no change. The early change in the diffusion parameters was enhanced by using high DWMRI. When high DWMRI was used, all responding lesions showed increase in the diffusion parameter and all nonresponding lesions showed no change or decrease. Response was determined by standard MRI 7 weeks posttherapy. The changes in the diffusion parameters measured 1 week after initiating treatment were correlated with later tumor response or no response (P <.006). This correlation was increased to P <.0006 when high DWMRI was used. The significant correlation between changes in diffusion parameters 1 week after initiating treatment and later tumor response or no response suggests the feasibility of using DWMRI for early, noninvasive prediction of tumor response. The ability to predict response may enable early termination of treatment in nonresponding patients, prevent additional toxicity, and allow for early changes in treatment.

Fast and sensitive optical toxicity bioassay based on dual wavelength analysis of bacterial ferricyanide reduction kinetics.

PubMed

Pujol-Vila, F; Vigués, N; Díaz-González, M; Muñoz-Berbel, X; Mas, J

2015-05-15

Global urban and industrial growth, with the associated environmental contamination, is promoting the development of rapid and inexpensive general toxicity methods. Current microbial methodologies for general toxicity determination rely on either bioluminescent bacteria and specific medium solution (i.e. Microtox(®)) or low sensitivity and diffusion limited protocols (i.e. amperometric microbial respirometry). In this work, fast and sensitive optical toxicity bioassay based on dual wavelength analysis of bacterial ferricyanide reduction kinetics is presented, using Escherichia coli as a bacterial model. Ferricyanide reduction kinetic analysis (variation of ferricyanide absorption with time), much more sensitive than single absorbance measurements, allowed for direct and fast toxicity determination without pre-incubation steps (assay time=10 min) and minimizing biomass interference. Dual wavelength analysis at 405 (ferricyanide and biomass) and 550 nm (biomass), allowed for ferricyanide monitoring without interference of biomass scattering. On the other hand, refractive index (RI) matching with saccharose reduced bacterial light scattering around 50%, expanding the analytical linear range in the determination of absorbent molecules. With this method, different toxicants such as metals and organic compounds were analyzed with good sensitivities. Half maximal effective concentrations (EC50) obtained after 10 min bioassay, 2.9, 1.0, 0.7 and 18.3 mg L(-1) for copper, zinc, acetic acid and 2-phenylethanol respectively, were in agreement with previously reported values for longer bioassays (around 60 min). This method represents a promising alternative for fast and sensitive water toxicity monitoring, opening the possibility of quick in situ analysis. Copyright © 2014 Elsevier B.V. All rights reserved.

Physiologically-based pharmacokinetic modelling of immune, reproductive and carcinogenic effects from contaminant exposure in polar bears (Ursus maritimus) across the Arctic.

PubMed

Dietz, Rune; Gustavson, Kim; Sonne, Christian; Desforges, Jean-Pierre; Rigét, Frank F; Pavlova, Viola; McKinney, Melissa A; Letcher, Robert J

2015-07-01

Polar bears (Ursus maritimus) consume large quantities of seal blubber and other high trophic marine mammals and consequently have some of the highest tissue concentrations of organohalogen contaminants (OHCs) among Arctic biota. In the present paper we carried out a risk quotient (RQ) evaluation on OHC-exposed polar bears harvested from 1999 to 2008 and from 11 circumpolar subpopulations spanning from Alaska to Svalbard in order to evaluate the risk of OHC-mediated reproductive effects (embryotoxicity, teratogenicity), immunotoxicity and carcinogenicity (genotoxicity). This RQ evaluation was based on the Critical Body Residue (CBR) concept and a Physiologically-Based Pharmacokinetic Modelling (PBPK) approach using OHC concentrations measured in polar bear adipose or liver tissue. The range of OHC concentrations within polar bear populations were as follows for adipose, sum polychlorinated biphenyls ∑PCBs (1797-10,537 ng/g lw), sum methylsulphone-PCB ∑MeSO2-PCBs (110-672 ng/g lw), sum chlordanes ∑CHLs (765-3477 ng/g lw), α-hexachlorocyclohexane α-HCH (8.5-91.3 ng/g lw), β-hexachlorocyclohexane β-HCH (65.5-542 ng/g lw), sum chlorbenzenes ∑ClBzs (145-304 ng/g lw), dichlorodiphenyltrichloroethane ∑DDTs (31.5-206 ng/g lw), dieldrin (69-249 ng/g lw), polybrominated diphenyl ethers ∑PBDEs (4.6-78.4 ng/g lw). For liver, the perfluorooctanesulfonic acid (PFOS) concentrations ranged from 231-2792 ng/g ww. The total additive RQ from all OHCs ranged from 4.3 in Alaska to 28.6 in East Greenland bears for effects on reproduction, immune health and carcinogenicity, highlighting the important result that the toxic effect threshold (i.e. RQ>1) was exceeded for all polar bear populations assessed. PCBs were the main contributors for all three effect categories, contributing from 70.6% to 94.3% of the total risk and a RQ between 3.8-22.5. ∑MeSO2-PCBs were the second highest effect contributor for reproductive and immunological effects (0.17

Single-particle spectroscopy of I-III-VI semiconductor nanocrystals: spectral diffusion and suppression of blinking by two-color excitation.

PubMed

Sharma, Dharmendar Kumar; Hirata, Shuzo; Bujak, Lukasz; Biju, Vasudevanpillai; Kameyama, Tatsuya; Kishi, Marino; Torimoto, Tsukasa; Vacha, Martin

2016-07-14

Ternary I-III-VI semiconductor nanocrystals have been explored as non-toxic alternatives to II-VI semiconductors for optoelectronic and sensing applications, but large photoluminescence spectral width and moderate brightness restrict their practical use. Here, using single-particle photoluminescence spectroscopy on nanocrystals of (AgIn)xZn2(1-x)S2 we show that the photoluminescence band is inhomogeneously broadened and that size distribution is the dominant factor in the broadening. The residual homogeneous linewidth of individual nanocrystals reaches up to 75% of the ensemble spectral width. Single nanocrystals undergo spectral diffusion which also contributes to the inhomogeneous band. Excitation with two lasers with energies above and below the bandgap reveals coexistence of two emitting donor states within one particle. Spectral diffusion in such particles is due to temporal activation and deactivation of one such state. Filling of a trap state with a lower-energy laser enables optical modulation of photoluminescence intermittency (blinking) and leads to an almost two-fold increase in brightness.

Cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (COMLA) combination sequential chemotherapy for advanced diffuse histiocytic lymphoma

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

Sweet, D.L.; Golomb, H.M.; Ultmann, J.E.

A program of combination sequential chemotherapy using cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (COMLA) was administered to 42 previously untreated patients with advanced diffuse histiocytic lymphoma. Twenty-three patients achieved a complete remission as determined by strict clinical restaging criteria. The observed median duration of survival for the complete responders is longer than 33 months. Eight patients achieved a partial response, with a median survival longer than 21 months. Eleven patients showed no response, with a median survival of 5 months. Toxicity was acceptable. None of the responders have shown central nervous system relapse. There was no difference inmore » response rates between patients with stage III or IV lymphoma or between asymptomatic or symptomatic patients. The COMLA program produces a high rate of complete and durable remissions and should be considered as an initial form of management of patients with advanced diffuse histiocytic lymphoma.« less

Interlayer utilization (including metal borides) for subsequent deposition of NSD films via microwave plasma CVD on 316 and 440C stainless steels

NASA Astrophysics Data System (ADS)

Ballinger, Jared

Diamond thin films have promising applications in numerous fields due to the extreme properties of diamonds in conjunction with the surface enhancement of thin films. Biomedical applications are numerous including temporary implants and various dental and surgical instruments. The unique combination of properties offered by nanostructured diamond films that make it such an attractive surface coating include extreme hardness, low obtainable surface roughness, excellent thermal conductivity, and chemical inertness. Regrettably, numerous problems exist when attempting to coat stainless steel with diamond generating a readily delaminated film: outward diffusion of iron to the surface, inward diffusion of carbon limiting necessary surface carbon precursor, and the mismatch between the coefficients of thermal expansion yielding substantial residual stress. While some exotic methods have been attempted to overcome these hindrances, the most common approach is the use of an intermediate layer between the stainless steel substrate and the diamond thin film. In this research, both 316 stainless steel disks and 440C stainless steel ball bearings were tested with interlayers including discrete coatings and graded, diffusion-based surface enhancements. Titanium nitride and thermochemical diffusion boride interlayers were both examined for their effectiveness at allowing for the growth of continuous and adherent diamond films. Titanium nitride interlayers were deposited by cathodic arc vacuum deposition on 440C bearings. Lower temperature diamond processing resulted in improved surface coverage after cooling, but ultimately, both continuity and adhesion of the nanostructured diamond films were unacceptable. The ability to grow quality diamond films on TiN interlayers is in agreement with previous work on iron and low alloy steel substrates, and the similarly seen inadequate adhesion strength is partially a consequence of the lacking establishment of an interfacial carbide phase. Surface boriding was implemented using the novel method of microwave plasma CVD with a mixture of hydrogen and diborane gases. On 440C bearings, dual phase boride layers of Fe2B and FeB were formed which supported adhered nanostructured diamond films. Continuity of the films was not seamless with limited regions remaining uncoated potentially corresponding to delamination of the film as evidenced by the presence of tubular structures presumably composed of sp2 bonded carbon. Surface boriding of 316 stainless steel discs was conducted at various powers and pressures to achieve temperatures ranging from 550-800 °C. The substrate boriding temperature was found to substantially influence the resultant interlayer by altering the metal boride(s) present. The lowest temperatures produced an interlayer where CrB was the single detected phase, higher temperatures yielded the presence of only Fe2B, and a combination of the two phases resulted from an intermediate boriding temperature. Compared with the more common, commercialized boriding methods, this a profound result given the problems posed by the FeB phase in addition to other advantages offered by CVD processes and microwave generated plasmas in general. Indentation testing of the boride layers revealed excellent adhesion strength for all borided interlayers, and above all, no evidence of cracking was observed for a sole Fe2B phase. As with boriding of 440C bearings, subsequent diamond deposition was achieved on these interlayers with substantially improved adhesion strength relative to diamond coated TiN interlayers. Both XRD and Raman spectroscopy confirmed a nanostructured diamond film with interfacial chromium carbides responsible for enhanced adhesion strength. Interlayers consisting solely of Fe2B have displayed an ability to support fully continuous nanostructured diamond films, yet additional study is required for consistent reproduction. This is in good agreement with initial work on pack borided high alloy steels to promote diamond film surface modification. The future direction for continued research of nanostructured diamond coatings on microwave plasma CVD borided stainless steel should further investigate the adhesion of both borided interlayers and subsequent NSD films in addition to short, interrupted diamond depositions to study the interlayer/diamond film interface.

Physicochemical characteristics and toxic effects of ozone-oxidized black carbon particles

NASA Astrophysics Data System (ADS)

Li, Qian; Shang, Jing; Zhu, Tong

2013-12-01

Black carbon (BC) or soot particles formed by combustion are ubiquitous in the atmosphere and have a significant effect on climate and human health. Oxidation can change the physicochemical characteristics of BC, thereby increasing its toxicity. The physicochemical properties of BC and ozone-oxidized BC are investigated in this study through transmission electron microscopy, X-ray photoelectron spectroscopy, diffuse reflectance infrared Fourier transform spectroscopy, ultraviolet-visible spectrophotometry, and electron paramagnetic resonance. The contents of oxygen-containing functional groups, hydrophilicity, water-soluble organic compounds, and free radicals increased after ozone treatment. The redox capacity and cytotoxicity of BC particles were enhanced by ozone oxidation as detected by dithiothreitol (DTT) and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assays. The redox activities of different BC particles are compared. Particle phase contributed significantly to total redox activity as detected by the DTT assay. Results indicate that BC particles that have undergone aging in the atmosphere may be more toxic and harmful to human health.

A new model integrating short- and long-term aging of copper added to soils

PubMed Central

Zeng, Saiqi; Li, Jumei; Wei, Dongpu

2017-01-01

Aging refers to the processes by which the bioavailability/toxicity, isotopic exchangeability, and extractability of metals added to soils decline overtime. We studied the characteristics of the aging process in copper (Cu) added to soils and the factors that affect this process. Then we developed a semi-mechanistic model to predict the lability of Cu during the aging process with descriptions of the diffusion process using complementary error function. In the previous studies, two semi-mechanistic models to separately predict short-term and long-term aging of Cu added to soils were developed with individual descriptions of the diffusion process. In the short-term model, the diffusion process was linearly related to the square root of incubation time (t1/2), and in the long-term model, the diffusion process was linearly related to the natural logarithm of incubation time (lnt). Both models could predict short-term or long-term aging processes separately, but could not predict the short- and long-term aging processes by one model. By analyzing and combining the two models, we found that the short- and long-term behaviors of the diffusion process could be described adequately using the complementary error function. The effect of temperature on the diffusion process was obtained in this model as well. The model can predict the aging process continuously based on four factors—soil pH, incubation time, soil organic matter content and temperature. PMID:28820888

The toxicity of rifampicin polylactic acid nanoparticles against Mycobacterium bovis BCG and human macrophage THP-1 cell line

NASA Astrophysics Data System (ADS)

Erokhina, M.; Rybalkina, E.; Barsegyan, G.; Onishchenko, G.; Lepekha, L.

2015-11-01

Tuberculosis is rapidly becoming a major health problem. The rise in tuberculosis incidence stimulates efforts to develop more effective delivery systems for the existing antituberculous drugs while decreasing the side effects. The nanotechnology may provide novel drug delivery tools allowing controlled drug release. Rifampicin is one of the main antituberculous drugs, characterized by high toxicity, and Poly (L-lactic acid) (PLLA) is a biodegradable polymer used for the preparation of encapsulated drugs. The aim of our work was to evaluate the toxicity of rifampicin-PLLA nanoparticles against Mycobacterium bovis BCG using human macrophage THP-1 cell line. Our data demonstrate that rifampicin-PLLA is effective against M. bovis BCG in the infected macrophages. The drug is inducing the dysfunction of mitochondria and apoptosis in the macrophages and is acting as a potential substrate of Pgp thereby modulating cell chemosensitivity. The severity of the toxic effects of the rifampicin-PLLA nanoparticles is increasing in a dose-dependent manner. We suggest that free rifampicin induces death of M. bovis BCG after PLLA degradation and diffusion from phago-lysosomes to cytoplasm causing mitochondria dysfunction and affecting the Pgp activity.

Toxicity evaluation of convection-enhanced delivery of small-molecule kinase inhibitors in naïve mouse brainstem.

PubMed

Zhou, Zhiping; Ho, Sharon L; Singh, Ranjodh; Pisapia, David J; Souweidane, Mark M

2015-04-01

Diffuse intrinsic pontine gliomas (DIPGs) are inoperable and lethal high-grade gliomas lacking definitive therapy. Platelet-derived growth factor receptor (PDGFR) and its downstream signaling molecules are the most commonly overexpressed oncogenes in DIPG. This study tested the effective concentration of PDGFR pathway inhibitors in cell culture and then toxicity of these small-molecule kinase inhibitors delivered to the mouse brainstem via convection-enhanced delivery (CED) for potential clinical application. Effective concentrations of small-molecule kinase inhibitors were first established in cell culture from a mouse brainstem glioma model. Sixteen mice underwent CED, a local drug delivery technique, of saline or of single and multidrug combinations of dasatinib (2 M), everolimus (20 M), and perifosine (0.63 mM) in the pons. Animals were kept alive for 3 days following the completion of infusion. No animals displayed any immediate or delayed neurological deficits postoperatively. Histological analysis revealed edema, microgliosis, acute inflammation, and/or axonal injury in the experimental animals consistent with mild acute drug toxicity. Brainstem CED of small-molecule kinase inhibitors in the mouse did not cause serious acute toxicities. Future studies will be necessary to evaluate longer-term safety to prepare for potential clinical application.

Folate Receptor Targeted Alpha-Therapy Using Terbium-149

PubMed Central

Müller, Cristina; Reber, Josefine; Haller, Stephanie; Dorrer, Holger; Köster, Ulli; Johnston, Karl; Zhernosekov, Konstantin; Türler, Andreas; Schibli, Roger

2014-01-01

Terbium-149 is among the most interesting therapeutic nuclides for medical applications. It decays by emission of short-range α-particles (Eα = 3.967 MeV) with a half-life of 4.12 h. The goal of this study was to investigate the anticancer efficacy of a 149Tb-labeled DOTA-folate conjugate (cm09) using folate receptor (FR)-positive cancer cells in vitro and in tumor-bearing mice. 149Tb was produced at the ISOLDE facility at CERN. Radiolabeling of cm09 with purified 149Tb resulted in a specific activity of ~1.2 MBq/nmol. In vitro assays performed with 149Tb-cm09 revealed a reduced KB cell viability in a FR-specific and activity concentration-dependent manner. Tumor-bearing mice were injected with saline only (group A) or with 149Tb-cm09 (group B: 2.2 MBq; group C: 3.0 MBq). A significant tumor growth delay was found in treated animals resulting in an increased average survival time of mice which received 149Tb-cm09 (B: 30.5 d; C: 43 d) compared to untreated controls (A: 21 d). Analysis of blood parameters revealed no signs of acute toxicity to the kidneys or liver in treated mice over the time of investigation. These results demonstrated the potential of folate-based α-radionuclide therapy in tumor-bearing mice. PMID:24633429

[Lipid peroxidation in thyroid tissue of people with diffuse toxic goiter].

PubMed

Rom-Boguslavskaia, E S; Somova, E V; Ovsiannikova, T N; Diageleva, E A; Karachentsev, Iu I; Asaula, V A

1997-01-01

The processes of lipids free-radical oxidation in euthyroid and thyrotoxic tissue samples of human thyroid gland were studied. It was shown, that the content of TBA-active lipid peroxidation products was considerably increased in thyrotoxic tissue of the thyroid, and the activity of antioxidant enzymes (catalase, glutation peroxidase) was decreased in it. Possible mechanism of the tissue lipoperoxide alternation under conditions of the thyroid hyperfunction is discussed.

Eco-friendly synthesis of TiO2, Au and Pt doped TiO2 nanoparticles for dye sensitized solar cell applications and evaluation of toxicity

NASA Astrophysics Data System (ADS)

Gopinath, K.; Kumaraguru, S.; Bhakyaraj, K.; Thirumal, S.; Arumugam, A.

2016-04-01

Driven by the demand of pure TiO2, Au and Pt doped TiO2 NPs were successfully synthesized using Terminalia arjuna bark extract. The eco-friendly synthesized NPs were characterized by UV-Vis-DRS, ATR-FT-IR, PL, XRD, Raman, SEM with EDX and TEM analysis. The synthesized NPs were investigation for dye sensitized solar cell applications. UV-Vis-Diffused Reflectance Spectra clearly showed that the expected TiO2 inter band absorption below 306 nm, incorporation of gold shows surface plasma resonant (SPR) near 555 nm and platinum incorporated TiO2 NPs shows absorbance at 460 nm. The energy conversion efficiency for Au doped TiO2 NPs when compared to pure and Pt doped TiO2 NPs. In addition to that, Au noble metal present TiO2 matrix and an improve open-circuit voltage (Voc) of DSSC. Synthesized NPs was evaluated into antibacterial and antifungal activities by disk diffusion method. It is observed that NPs have not shown any activities in all tested bacterial and fungal strains. In this eco-friendly synthesis method to provide non toxic and environmental friendly nanomaterials can be used for solar energy device application.

Bioavailable cadmium during the bioremediation of phenanthrene-contaminated soils using the diffusive gradients in thin-film technique.

PubMed

Amezcua-Allieri, M A; Rodríguez-Vázquez, R

2006-03-01

To study the impact of fungal bioremediation of phenanthrene on trace cadmium solid-solution fluxes and solution phase concentration. The bioremediation of phenanthrene in soils was performed using the fungus Penicillium frequentans. Metal behaviour was evaluated by the techniques of diffusive gradient in thin-films (DGT) and filtration. Fluxes of cadmium (Cd) show a significant (P < 0.002) increase after the start of bioremediation, indicating that the bioremediation process itself releases significant amount of Cd into solution from the soil solid-phase. Unlike DGT devices, the solution concentration from filtration shows a clear bimodal distribution. We postulate that the initial action of the fungi is most likely to breakdown the surface of the solid phase to smaller, 'solution-phase' material (<0.45 microm) leading to a peak in Cd concentration in solution. Phenanthrene removal from soils by bioremediation ironically results in the mobilization of another toxic pollutant (Cd). Bioremediation of organic pollutants in contaminated soil will likely lead to large increases in the mobilization of toxic metals, increasing metal bio-uptake and incorporation into the wider food chain. Bioremediation strategies need to account for this behaviour and further research is required both to understand the generality of this behaviour and the operative mechanisms.

Coliform bacteria isolated from recreational lakes carry class 1 and class 2 integrons and virulence-associated genes.

PubMed

Koczura, R; Krysiak, N; Taraszewska, A; Mokracka, J

2015-08-01

To characterize the integron-harbouring Gram-negative bacteria in recreational lakes, with focus on the genetic content of integrons, antimicrobial resistance profiles and virulence-associated genes. The presence and structure of integrons in coliform bacteria isolated from the water of four recreational lakes located in Poznań, Poland, was determined by PCR method. Antimicrobial resistance testing was done by disc diffusion method. Virulence-associated genes in integron-bearing Escherichia coli isolates were detected by PCR. A total of 155 integron-bearing strains of coliform bacteria were cultured. Sequence analysis showed the presence of dfrA7, aadA1, dfrA1-aadA1, dfrA17-aadA5 and dfrA12-orfF-aadA2 gene cassette arrays in class 1 integrons and dfrA1-sat2-aadA1 in class 2 integrons. Higher frequency of integron-positive bacteria and higher antimicrobial resistance ranges were noted in colder months (January and November) compared with spring and summer months. The integron-harbouring E. coli carried up to nine virulence-associated genes, with the highest frequency of kpsMT (84.6%) and traT (783%), coding for group 2 capsule and determining human serum resistance respectively. Integron-bearing multidrug resistant coliform bacteria carrying virulence genes are present in waters of recreational lakes. This study presents antimicrobial resistance and virulence-associated genes in integron-bearing coliform bacteria present in the waters of recreational lakes, which showed that multidrug resistant bacteria with virulence traits might pose a threat to public health. Moreover, the presence of genes typical for enterotoxigenic and Shiga toxin-producing E. coli is a concern. © 2015 The Society for Applied Microbiology.

Small, high-pressure ratio compressor mechanical acceptance test, volume 2

NASA Technical Reports Server (NTRS)

Metty, G. R.; Shoup, W. I.

1973-01-01

The fabrication and mechanical testing of the high-pressure-ratio compressor are reported. Mechanical testing was performed to demonstrate overspeed capability, adequate rotor dynamics, electrical isolation of the gas bearing trunnion mounted diffuser and shroud and the effect of operating parameters (speed and pressure ratio) on clearance of the compressor test rig. The speed range covered was 20 to 120 percent of rated speed (80,000 rpm). Following these tests an acceptance test which consisted of a 5 hour run at 80,000 rpm was made with approximately design impeller to shroud clearances. For Vol. 1, see N73-26483.

Bacteria transport through porous media. Annual report, December 31, 1984

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

Yen, T.F.

1986-09-01

The following five chapters in this report have been processed separately for inclusion in the Energy Data Base: (1) theoretical model of convective diffusion of motile and non-motile bacteria toward solid surfaces; (2) interfacial electrochemistry of oxide surfaces in oil-bearing sands and sandstones; (3) effects of sodium pyrophosphate additive on the ''huff and puff''/nutrient flooding MEOR process; (4) interaction of Escherichia coli B, B/4, and bacteriophage T4D with Berea sandstone rock in relation to enhanced oil recovery; and (5) transport of bacteria in porous media and its significance in microbial enhanced oil recovery.

Chromium in urban sediment particulates: an integrated micro-chemical and XANES study

NASA Astrophysics Data System (ADS)

Taylor, Kevin; Byrne, Patrick; Hudson-Edwards, Karen

2015-04-01

Chromium is generally common within the urban sediment cascade as a result of abundant industrial and transport-related sources. The risks that Cr-bearing particles pose to ecosystems and humans depend on the solid phase chemical speciation of Cr in the particles. In this study, we use bulk chemical digests, sequential chemical extraction analysis, electron microscopy, electron microprobe and microfocus XANES analysis to describe the solid-phase speciation of Cr in urban particulate matter from both aquatic sediment and road dust sediment (RDS) in Manchester, UK. Cr-bearing grains within RDS are predominantly iron oxide grains, commonly of goethite or haematite mineralogy, but Cr-bearing silicate glass grains are also present. Iron oxide glass grains most likely have sorbed Cr, and derive from the rusting of Cr-steel particles from vehicles. Electron microprobe analysis indicates concentrations of Cr up to 3200 μg/g in these grains, and XANES analysis indicates that Cr(III) is the dominant oxidation state, with some trace amounts of Cr(VI). Cr-bearing grains within aquatic sediments are dominated by alumino-silicate glass grains derived from industrial waste. These grains contain Cr-rich areas with up to 19% Cr2O3 and XANES analysis indicates that Cr is present as Cr(III). The dominance of Cr(III) in these urban particulate grains suggests limited bioavailability or toxicity. However, the presence within two markedly different grain types (iron oxides and silicate glasses) indicates that the long-term geochemical behaviour and environmental risk of RDS and the aquatic sediments studied are likely to be quite different. These findings highlight the importance of understanding sources of metal contaminants in urban environments and the geochemical processes that affect their transfer through the urban sediment cascade and the wider river basin.

Photoactivated in Vitro Anticancer Activity of Rhenium(I) Tricarbonyl Complexes Bearing Water-Soluble Phosphines.

PubMed

Marker, Sierra C; MacMillan, Samantha N; Zipfel, Warren R; Li, Zhi; Ford, Peter C; Wilson, Justin J

2018-02-05

Fifteen water-soluble rhenium compounds of the general formula [Re(CO) 3 (NN)(PR 3 )] + , where NN is a diimine ligand and PR 3 is 1,3,5-triaza-7-phosphaadamantane (PTA), tris(hydroxymethyl)phosphine (THP), or 1,4-diacetyl-1,3,7-triaza-5-phosphabicylco[3.3.1]nonane (DAPTA), were synthesized and characterized by multinuclear NMR spectroscopy, IR spectroscopy, and X-ray crystallography. The complexes bearing the THP and DAPTA ligands exhibit triplet-based luminescence in air-equilibrated aqueous solutions with quantum yields ranging from 3.4 to 11.5%. Furthermore, the THP and DAPTA complexes undergo photosubstitution of a CO ligand upon irradiation with 365 nm light with quantum yields ranging from 1.1 to 5.5% and sensitize the formation of 1 O 2 with quantum yields as high as 70%. In contrast, all of the complexes bearing the PTA ligand are nonemissive and do not undergo photosubstitution upon irradiation with 365 nm light. These compounds were evaluated as photoactivated anticancer agents in human cervical (HeLa), ovarian (A2780), and cisplatin-resistant ovarian (A2780CP70) cancer cell lines. All of the complexes bearing THP and DAPTA exhibited a cytotoxic response upon irradiation with minimal toxicity in the absence of light. Notably, the complex with DAPTA and 1,10-phenanthroline gave rise to an IC 50 value of 6 μM in HeLa cells upon irradiation, rendering it the most phototoxic compound in this library. The nature of the photoinduced cytotoxicity of this compound was explored in further detail. These data indicate that the phototoxic response may result from the release of both CO and the rhenium-containing photoproduct, as well as the production of 1 O 2 .

Effects of cyanamide and clofibrate on the enzymes of ethanol oxydation and on ethanol consumption in the rat.

PubMed

Lamboeuf, Y; De Saint Blanquat, G

1980-01-01

The action of cyanamide and of clofibrate was studied on the voluntary drinking behaviour of alcohol intoxicated animals and also on the enzymes of ethyl oxydation. Both substances reduce alcohol consumption by about 35% and cause metabolic modifications: inhibition of aldehyde dehydrogenase and of catalase by cyanamide; activation of alcohol- and aldehyde-dehydrogenases by clofibrate. These effects are constantly found in most of the tissues of the rat. The results are discussed bearing in mind the relationships between alcohol metabolism, acetaldehyde metabolism, the toxicity of alcohol and the drinking behaviour.

Lethality In Mice Following Localized Photodynamic Therapy

NASA Astrophysics Data System (ADS)

Ferrario, Angela; Gomer, Charles J.; Murphree, A. L.

1989-06-01

Porphyrin photodynamic therapy directed specifically to the hind leg of various strains of mice was found to induce a high percentage of lethality at dosages which would be required to achieve cures in tumor bearing mice. Toxicity was observed in both pigmented and albino mouse strains. An inverse relationship between light dose rate and lethality was documented. Anti-coagulant drugs and anti-inflammatory agents which inhibit cyclo-oxygenase had protective effects. The response induced by localized PDT appears to mimic that of a classical traumatic shock syndrome and may be limited to PDT in small animals such as mice.

THE CARDIOVASCULAR SYSTEM IN TYPE 2 DIABETES MELLITUS AND THYROID DISORDERS IN THE ABSENCE OF THYROID GLAND DYSFUNCTION.

PubMed

Ballyizek, M F; Ignat'eva Pa

The state of the cardiovascular system was studied in patients with type 2 diabetes mellitus and thyroid disorders in the absence of thyroid gland dysfunction. 76.9% of the 302 patients with DM2 had thyroid pathology; in 23,8% it was not previously diagnosed. We compared euthyroid patients with DM2 without thy'ropathies and with diffuse-nodular changes largely in the form of difuse- multinodular non-toxic goiter and autoinnnune thyroiditis (AIT). It was demonstrated that enhanced frequency of thyroid disorders is related to DM2 duration and vascular complications. The predominant thyroid pathology in DM2 was diffuse-multinodular non-toxic goiter followed by autoimnune thvroiditis. Nodular forms in AIT without DM2 are rare whereas multinodularformns in the patients with DM2 and AIT occur much more fequently. Node formation is related to such DM2 complications as diabetic nephropathy, angiopathy, and retinopathy. The study showed that the frequency of both non-specific clinical changes characteristic of thyroid dysfunction and of specific cardiological manifestations in euthyroid patients with DM2 and thyroid pathology signficantly increases especially in the presence of AIT and anti-thyreoperoxidase antibodies, regardless the form of thyropathy. It may be due to imimuno-inflammatory cross talk between thyroid and myocardial tissues. Patients with DM2 and diffuse-nodular changes in the thyroid gland more frequently presented with dif ferent forms of atrial fibrillation and high-grade ventricular extrasystole than patients with AIT or DM2 without thyropathies. It is concluded that euthyroid patients with DM2 need their thyroid function to be regularly monitored. The development of examination algorithm is an object of further studies.

Chemotherapy-Refractory Diffuse Large B-Cell Lymphoma and Indolent B-Cell Malignancies Can Be Effectively Treated With Autologous T Cells Expressing an Anti-CD19 Chimeric Antigen Receptor

PubMed Central

Kochenderfer, James N.; Dudley, Mark E.; Kassim, Sadik H.; Somerville, Robert P.T.; Carpenter, Robert O.; Stetler-Stevenson, Maryalice; Yang, James C.; Phan, Giao Q.; Hughes, Marybeth S.; Sherry, Richard M.; Raffeld, Mark; Feldman, Steven; Lu, Lily; Li, Yong F.; Ngo, Lien T.; Goy, Andre; Feldman, Tatyana; Spaner, David E.; Wang, Michael L.; Chen, Clara C.; Kranick, Sarah M.; Nath, Avindra; Nathan, Debbie-Ann N.; Morton, Kathleen E.; Toomey, Mary Ann; Rosenberg, Steven A.

2015-01-01

Purpose T cells can be genetically modified to express an anti-CD19 chimeric antigen receptor (CAR). We assessed the safety and efficacy of administering autologous anti-CD19 CAR T cells to patients with advanced CD19+ B-cell malignancies. Patients and Methods We treated 15 patients with advanced B-cell malignancies. Nine patients had diffuse large B-cell lymphoma (DLBCL), two had indolent lymphomas, and four had chronic lymphocytic leukemia. Patients received a conditioning chemotherapy regimen of cyclophosphamide and fludarabine followed by a single infusion of anti-CD19 CAR T cells. Results Of 15 patients, eight achieved complete remissions (CRs), four achieved partial remissions, one had stable lymphoma, and two were not evaluable for response. CRs were obtained by four of seven evaluable patients with chemotherapy-refractory DLBCL; three of these four CRs are ongoing, with durations ranging from 9 to 22 months. Acute toxicities including fever, hypotension, delirium, and other neurologic toxicities occurred in some patients after infusion of anti-CD19 CAR T cells; these toxicities resolved within 3 weeks after cell infusion. One patient died suddenly as a result of an unknown cause 16 days after cell infusion. CAR T cells were detected in the blood of patients at peak levels, ranging from nine to 777 CAR-positive T cells/μL. Conclusion This is the first report to our knowledge of successful treatment of DLBCL with anti-CD19 CAR T cells. These results demonstrate the feasibility and effectiveness of treating chemotherapy-refractory B-cell malignancies with anti-CD19 CAR T cells. The numerous remissions obtained provide strong support for further development of this approach. PMID:25154820

Improving risk assessment of color additives in medical device polymers.

PubMed

Chandrasekar, Vaishnavi; Janes, Dustin W; Forrey, Christopher; Saylor, David M; Bajaj, Akhil; Duncan, Timothy V; Zheng, Jiwen; Riaz Ahmed, Kausar B; Casey, Brendan J

2018-01-01

Many polymeric medical device materials contain color additives which could lead to adverse health effects. The potential health risk of color additives may be assessed by comparing the amount of color additive released over time to levels deemed to be safe based on available toxicity data. We propose a conservative model for exposure that requires only the diffusion coefficient of the additive in the polymer matrix, D, to be specified. The model is applied here using a model polymer (poly(ether-block-amide), PEBAX 2533) and color additive (quinizarin blue) system. Sorption experiments performed in an aqueous dispersion of quinizarin blue (QB) into neat PEBAX yielded a diffusivity D = 4.8 × 10 -10 cm 2  s -1 , and solubility S = 0.32 wt %. On the basis of these measurements, we validated the model by comparing predictions to the leaching profile of QB from a PEBAX matrix into physiologically representative media. Toxicity data are not available to estimate a safe level of exposure to QB, as a result, we used a Threshold of Toxicological Concern (TTC) value for QB of 90 µg/adult/day. Because only 30% of the QB is released in the first day of leaching for our film thickness and calculated D, we demonstrate that a device may contain significantly more color additive than the TTC value without giving rise to a toxicological concern. The findings suggest that an initial screening-level risk assessment of color additives and other potentially toxic compounds found in device polymers can be improved. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 310-319, 2018. © 2017 Wiley Periodicals, Inc.

A Phase I Clinical Trial of Systemically Delivered NEMO Binding Domain Peptide in Dogs with Spontaneous Activated B-Cell like Diffuse Large B-Cell Lymphoma

PubMed Central

Habineza Ndikuyeze, Georges; Gaurnier-Hausser, Anita; Patel, Reema; Baldwin, Albert S.; May, Michael J.; Flood, Patrick; Krick, Erika; Propert, Kathleen J.; Mason, Nicola J.

2014-01-01

Activated B-Cell (ABC) Diffuse Large B-Cell Lymphoma (DLBCL) is a common, aggressive and poorly chemoresponsive subtype of DLBCL, characterized by constitutive canonical NF-κB signaling. Inhibition of NF-κB signaling leads to apoptosis of ABC-DLBCL cell lines, suggesting targeted disruption of this pathway may have therapeutic relevance. The selective IKK inhibitor, NEMO Binding Domain (NBD) peptide effectively blocks constitutive NF-κB activity and induces apoptosis in ABC-DLBCL cells in vitro. Here we used a comparative approach to determine the safety and efficacy of systemic NBD peptide to inhibit constitutive NF-κB signaling in privately owned dogs with spontaneous newly diagnosed or relapsed ABC-like DLBCL. Malignant lymph nodes biopsies were taken before and twenty-four hours after peptide administration to determine biological effects. Intravenous administration of <2 mg/kg NBD peptide was safe and inhibited constitutive canonical NF-κB activity in 6/10 dogs. Reductions in mitotic index and Cyclin D expression also occurred in a subset of dogs 24 hours post peptide and in 3 dogs marked, therapeutically beneficial histopathological changes were identified. Mild, grade 1 toxicities were noted in 3 dogs at the time of peptide administration and one dog developed transient subclinical hepatopathy. Long term toxicities were not identified. Pharmacokinetic data suggested rapid uptake of peptide into tissues. No significant hematological or biochemical toxicities were identified. Overall the results from this phase I study indicate that systemic administration of NBD peptide is safe and effectively blocks constitutive NF-κB signaling and reduces malignant B cell proliferation in a subset of dogs with ABC-like DLBCL. These results have potential translational relevance for human ABC-DLBCL. PMID:24798348

Migration of 75Se(IV) in crushed Beishan granite: Effects of the iron content.

PubMed

He, Jiangang; Ma, Bin; Kang, Mingliang; Wang, Chunli; Nie, Zhe; Liu, Chunli

2017-02-15

The diffusion of selenite (labeled with 75 Se) in compacted Beishan granite (BsG) was investigated using the in-diffusion capillary method at pH values from ∼2.0 to ∼11.0 under oxic and anoxic conditions. The results indicate that the apparent diffusion coefficient (D a ) values of selenite in BsG always reached the minimum at approximately pH 5. Unexpectedly, the D a values under oxic conditions are nearly one order of magnitude lower than those under the anoxic conditions. Further characterization reveals the existence of redox-sensitive Fe(II)-containing components, which can be responsible for the great difference in D a values. Fe(2p) X-ray photoelectron spectroscopy (XPS) results show that more Fe(III)-oxyhydroxide coating is formed on the granite's surface under aerobic conditions than is formed under anaerobic conditions. Correspondingly, Se(3d) spectra indicate that more selenium is sorbed under oxic conditions, and the sorbed amount always reached the maximum at pH values from ∼4 to ∼5. A linear combination fit of X-ray absorption near edge structure (XANES) spectroscopy data revealed that Se(0) was formed under anoxic condition and that selenite preferred to form inner-sphere complexes with Fe(III)-oxyhydroxide. Overall, this study indicates that natural Fe-bearing minerals can greatly attenuate selenite diffusion and the retardation would be enhanced under aerobic conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

[The leadership style as a mitigator of the insurgence of mobbing risk. Results from an empirical research on Italian nurses].

PubMed

Caporale, Loretta; Palese, Alvisa; Bortoluzzi, Guido

2012-01-01

The influence of the organizational factors in mobbing onset, is supported by several studies. The leadership style is considered as one of its main antecedents. To investigate the relation between the leadership style adopted by the Nurse Coordinator and the diffusion of "negative actions", main indicator and antecedent of mobbing onset. Empirical study that involved 175 nurses and obstetricians of a Public Hospital Corporation in North Italy. Data has been collected via a semi-structured and anonymous questionnaire. The results confirm the hypothesis that the adoption of a non-collaborative leadership style goes with a greater diffusion of "negative actions" among the nurses. To intervene on organizational variables, such as the leadership style, allows to reduce the working unease and, therefore, the factors which are linked to it and which bear on the provided relief quality. The results of this study underline the Nurse Coordinator role in preventing and thwarting the onset of "negative actions", which are a potential source for mobbing onset.

Dynamic Monte Carlo description of thermal desorption processes

NASA Astrophysics Data System (ADS)

Weinketz, Sieghard

1994-07-01

The applicability of the dynamic Monte Carlo method of Fichthorn and Weinberg, in which the time evolution of a system is described in terms of the absolute number of different microscopic possible events and their associated transition rates, is discussed for the case of thermal desorption simulations. It is shown that the definition of the time increment at each successful event leads naturally to the macroscopic differential equation of desorption, in the case of simple first- and second-order processes in which the only possible events are desorption and diffusion. This equivalence is numerically demonstrated for a second-order case. In the sequence, the equivalence of this method with the Monte Carlo method of Sales and Zgrablich for more complex desorption processes, allowing for lateral interactions between adsorbates, is shown, even though the dynamic Monte Carlo method does not bear their limitation of a rapid surface diffusion condition, thus being able to describe a more complex ``kinetics'' of surface reactive processes, and therefore be applied to a wider class of phenomena, such as surface catalysis.

Determination of Trace Metals, Moisture, pH and Assessment of Potential Toxicity of Selected Smokeless Tobacco Products

PubMed Central

Prabhakar, V.; Jayakrishnan, G.; Nair, S. V.; Ranganathan, B.

2013-01-01

The characterization and classification of smokeless tobacco products has been a continuously evolving process. This is based on a number of different parameters like nicotine content, moisture content, amount of heavy metals, pH, and in vitro cytotoxicity assays. Their contexts often vary between countries, research institutions, and legal requirements. The categorisation of these products is quite challenging due to the diffused sample sizes, diverse array of branded products on offer, and the absence of a centralized manufacturing facility. This study aims at a systematic classification of 10 smokeless tobacco product samples from the retail market based on their potential toxicity upon long-term use. The estimation of potential toxicity follows a well-established method that employs the concentration of toxic metals in the different samples. The potential toxicity as well as heavy metal concentrations of the smokeless tobacco products analysed was found to be much higher than acceptable limits. For instance, the levels of lead, cadmium, copper and zinc of 2.5, 1, 4 and 23 ppm, respectively, are well above their recommended limits. The results from the study indicate that chronic use of smokeless tobacco products is a significant health risk, especially in the vulnerable population. Further studies of this nature will help establish a toxicological fingerprint on the diverse class of products that floods the market now. PMID:24082341

Bioremediation of copper-contaminated soils by bacteria.

PubMed

Cornu, Jean-Yves; Huguenot, David; Jézéquel, Karine; Lollier, Marc; Lebeau, Thierry

2017-02-01

Although copper (Cu) is an essential micronutrient for all living organisms, it can be toxic at low concentrations. Its beneficial effects are therefore only observed for a narrow range of concentrations. Anthropogenic activities such as fungicide spraying and mining have resulted in the Cu contamination of environmental compartments (soil, water and sediment) at levels sometimes exceeding the toxicity threshold. This review focuses on the bioremediation of copper-contaminated soils. The mechanisms by which microorganisms, and in particular bacteria, can mobilize or immobilize Cu in soils are described and the corresponding bioremediation strategies-of varying levels of maturity-are addressed: (i) bioleaching as a process for the ex situ recovery of Cu from Cu-bearing solids, (ii) bioimmobilization to limit the in situ leaching of Cu into groundwater and (iii) bioaugmentation-assisted phytoextraction as an innovative process for in situ enhancement of Cu removal from soil. For each application, the specific conditions required to achieve the desired effect and the practical methods for control of the microbial processes were specified.

Oral treatment with a rattlesnake native polypeptide crotamine efficiently inhibits the tumor growth with no potential toxicity for the host animal and with suggestive positive effects on animal metabolic profile.

PubMed

Campeiro, Joana D; Marinovic, Marcelo P; Carapeto, Fernando Cintra; Dal Mas, Caroline; Monte, Gabriela Guilherme; Carvalho Porta, Lucas; Nering, Marcela B; Oliveira, Eduardo B; Hayashi, Mirian A F

2018-02-01

The efficacy of crotamine as antitumoral was first demonstrated by daily intraperitoneal (IP) injections of low doses of this toxin in an animal model bearing melanoma tumors. Significant inhibition of tumor growth and increased lifespan of mice bearing tumor was also noticed after 21 consecutive days of this daily IP administration of crotamine. However, due to the limited acceptance of treatments by IP route in clinical conditions, herein, we evaluated the antitumor effect of this native polypeptide employing the oral route. The efficacy of crotamine in inhibiting the melanoma growth in vivo, even after passing through the gastrointestinal tract of the animal, was confirmed here. In addition, biochemical biomarkers and also histopathological analysis showed both the absence of any potential toxic effects in tissues or organs of the animal in which the highest accumulation of crotamine is expected. Interestingly, a reduction of weight gain was observed mainly in animals with tumor treated with crotamine by IP route, but not by oral administration. Albeit, oral administered crotamine was able to significantly decrease the body weight gain of healthy animals without tumor. Taking advantage of this same experimental animal models receiving crotamine by oral route, it was possible to show metabolic changes as the increased capacity of glucose clearance, which was accompanied by a reduction of the total cholesterol, and by increased high-density lipoprotein levels, both observed mainly in the absence of tumor. Triglycerides and low-density lipoprotein were also significantly decreased, but only in the absence of tumor. Taken together, these data suggest a clear trend for metabolic positive effects and mischaracterize unhealthy condition of animals, with or without tumors, treated with crotamine for 21 days. In addition, this study confirmed the efficacy of crotamine administered by oral route as antitumor agent, which besides the additional advantage of administration convenience and decreased risk of toxic effects, allowed the serendipitous observation of several positive metabolic effects on treated animals.

Polymeric membrane materials: new aspects of empirical approaches to prediction of gas permeability parameters in relation to permanent gases, linear lower hydrocarbons and some toxic gases.

PubMed

Malykh, O V; Golub, A Yu; Teplyakov, V V

2011-05-11

Membrane gas separation technologies (air separation, hydrogen recovery from dehydrogenation processes, etc.) use traditionally the glassy polymer membranes with dominating permeability of "small" gas molecules. For this purposes the membranes based on the low free volume glassy polymers (e.g., polysulfone, tetrabromopolycarbonate and polyimides) are used. On the other hand, an application of membrane methods for VOCs and some toxic gas recovery from air, separation of the lower hydrocarbons containing mixtures (in petrochemistry and oil refining) needs the membranes with preferable penetration of components with relatively larger molecular sizes. In general, this kind of permeability is characterized for rubbers and for the high free volume glassy polymers. Data files accumulated (more than 1500 polymeric materials) represent the region of parameters "inside" of these "boundaries." Two main approaches to the prediction of gas permeability of polymers are considered in this paper: (1) the statistical treatment of published transport parameters of polymers and (2) the prediction using model of ≪diffusion jump≫ with consideration of the key properties of the diffusing molecule and polymeric matrix. In the frames of (1) the paper presents N-dimensional methods of the gas permeability estimation of polymers using the correlations "selectivity/permeability." It is found that the optimal accuracy of prediction is provided at n=4. In the frames of the solution-diffusion mechanism (2) the key properties include the effective molecular cross-section of penetrating species to be responsible for molecular transportation in polymeric matrix and the well known force constant (ε/k)(eff i) of {6-12} potential for gas-gas interaction. Set of corrected effective molecular cross-section of penetrant including noble gases (He, Ne, Ar, Kr, Xe), permanent gases (H(2), O(2), N(2), CO), ballast and toxic gases (CO(2), NO(,) NO(2), SO(2), H(2)S) and linear lower hydrocarbons (CH(4), C(2)H(6), C(3)H(8), C(4)H(10), C(2)H(4), C(3)H(6), C(4)H(8) - 1, C(2)H(2), C(3)H(4)-m (methylacetylene) and C(3)H(4)-a (allen) is determined by using two above mentioned approaches. All of this allows calculating preliminary the permeability parameters of above mentioned gases for most part of known polymers based on limited experimental data. The new correlations suggested demonstrate that the available free volume of polymeric matrix plays an important role in providing of rate and selectivity of gas diffusion for glassy-like polymers; the rate and selectivity of gas diffusion in rubbers is affected mainly by cohesion energy density (CED) the both polymer parameters being calculated by traditional additive group contributions technique. Results of present study are demonstrated by calculation of expected permeability parameters in relation to lower hydrocarbons and some toxic gases for polynorbornene based polymers, PIM and PTMSP outlining potential of practical application for new membrane polymers. Copyright © 2010 Elsevier B.V. All rights reserved.

A mathematical model of diffusion from a steady source of short duration in a finite mixing layer

NASA Astrophysics Data System (ADS)

Bianconi, Roberto; Tamponi, Matteo

This paper presents an analytical unsteady-state solution to the atmospheric dispersion equation for substances subject to chemical-physical decay in a finite mixing layer for releases of short duration. This solution is suitable for describing critical events relative to accidental release of toxic, flammable or explosive substances. To implement the solution, the Modello per Rilasci a Breve Termine (MRBT) code has been developed, for some characteristics parameters of which the results of the sensitivity analysis are presented. Moreover some examples of application to the calculation of exposure to toxic substances and to the determination of the ignition field of flammable substances are described. Finally, the mathematical model described can be used to interpret the phenomenon of pollutant accumulation.

5-ALA based photodynamic management of glioblastoma

NASA Astrophysics Data System (ADS)

Rühm, Adrian; Stepp, Herbert; Beyer, Wolfgang; Hennig, Georg; Pongratz, Thomas; Sroka, Ronald; Schnell, Oliver; Tonn, Jörg-Christian; Kreth, Friedrich-Wilhelm

2014-03-01

Objective: Improvement of the clinical outcome of glioblastoma (GBM) patients by employment of fluorescence and photosensitization on the basis of 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX). Methods: In this report the focus is laid on the use of tumor selective PpIX fluorescence for stereotactic biopsy sampling and intra-operative treatment monitoring. In addition, our current concept for treatment planning is presented. For stereotactic interstitial photodynamic therapy (iPDT), radial diffusers were implanted into the contrast enhancing tumor volume. Spectroscopic measurements of laser light transmission and fluorescence between adjacent fibers were performed prior, during and post PDT. Results: PpIX concentrations in primary glioblastoma tissue show high intra- and inter-patient variability, but are usually sufficient for an effective PDT. During individual treatment attempts with 5-ALA based GBM-iPDT, transmission and fluorescence measurements between radial diffusers gave the following results: 1. In some cases, transmission after PDT is considerably reduced compared to the value before PDT, which may be attributable to a depletion of oxygenated hemoglobin and/or diffuse bleeding. 2. PpIX fluorescence is efficiently photobleached during PDT in all cases. Conclusion: iPDT with assessment of PpIX fluorescence and photobleaching is a promising treatment option. Individualization of treatment parameters appears to bear a potential to further improve clinical outcomes.

Paleotemperatures at the lunar surfaces from open system behavior of cosmogenic 38Ar and radiogenic 40Ar

DOE PAGES

Shuster, David L.; Cassata, William S.

2015-02-10

The simultaneous diffusion of both cosmogenic 38Ar and radiogenic 40Ar from solid phases is controlled by the thermal conditions of rocks while residing near planetary surfaces. Combined observations of 38Ar/ 37Ar and 40Ar/ 39Ar ratios during stepwise degassing analyses of neutron-irradiated Apollo samples can distinguish between diffusive loss of Ar due to solar heating of the rocks and that associated with elevated temperatures during or following impact events; the data provide quantitative constraints on the durations and temperatures of each process. From sequentially degassed 38Ar/ 37Ar ratios can be calculated a spectrum of apparent 38Ar exposure ages versus the cumulativemore » release fraction of 37Ar, which is particularly sensitive to conditions at the lunar surface typically over ~106–108 year timescales. Due to variable proportions of K- and Ca-bearing glass, plagioclase and pyroxene, with variability in the grain sizes of these phases, each sample will have distinct sensitivity to, and therefore different resolving power on, past near-surface thermal conditions. Furthermore, we present the underlying assumptions, and the analytical and numerical methods used to quantify the Ar diffusion kinetics in multi-phase whole-rock analyses that provide these constraints.« less

Optimal choice of pH for toxicity and bioaccumulation studies of ionizing organic chemicals.

PubMed

Rendal, Cecilie; Kusk, Kresten Ole; Trapp, Stefan

2011-11-01

It is recognized that the pH of exposure solutions can influence the toxicity and bioaccumulation of ionizing compounds. The present study investigates whether it can be considered a general rule that an ionizable compound is more toxic and more bioaccumulative when in the neutral state. Three processes were identified to explain the behavior of ionizing compounds with changing pH: the change in lipophilicity when a neutral compound becomes ionized, electrical attraction, and the ion trap. The literature was screened for bioaccumulation and toxicity tests of ionizing organic compounds performed at multiple pH levels. Toxicity and bioconcentration factors (BCFs) were higher for acids at lower pH values, whereas the opposite was true for bases. The effect of pH was most pronounced when pH - pK(a) was in the range of -1 to 3 for acids, and -3 to 1 for bases. The factor by which toxicity and BCF changed with pH was correlated with the lipophilicity of the compound (log K(OW) of the neutral compound). For both acids and bases, the correlation was positive, but it was significant only for acids. Because experimental data in the literature were limited, results were supplemented with model simulations using a dynamic flux model based on the Fick-Nernst-Planck diffusion equation known as the cell model. The cell model predicts that bases with delocalized charges may in some cases show declining bioaccumulation with increasing pH. Little information is available for amphoteric and zwitterionic compounds; however, based on simulations with the cell model, it is expected that the highest toxicity and bioaccumulation of these compounds will be found where the compounds are most neutral, at the isoelectric point. Copyright © 2011 SETAC.

Where is iron in erionite? A multidisciplinary study on fibrous erionite-Na from Jersey (Nevada, USA)

PubMed Central

Gualtieri, Alessandro F.; Gandolfi, Nicola Bursi; Pollastri, Simone; Pollok, Kilian; Langenhorst, Falko

2016-01-01

Fibrous erionite is a mineral fibre of great concern but to date mechanisms by which it induces cyto- and geno-toxic damage, and especially the role of iron associated to this zeolite species, remain poorly understood. One of the reasons is that we still don’t know exactly where iron is in natural erionite. This work is focused on fibrous erionite-Na from Jersey (Nevada, USA) and attempts to draw a general model of occurrence of iron in erionite and relationship with toxicity mechanisms. It was found that iron is present as 6-fold coordinated Fe3+ not part of the zeolite structure. The heterogeneous nature of the sample was revealed as receptacle of different iron-bearing impurities (amorphous iron-rich nanoparticles, micro-particles of iron oxides/hydroxides, and flakes of nontronite). If iron is not part of the structure, its role should be considered irrelevant for erionite toxicity, and other factors like biopersistence should be invoked. An alternative perspective to the proposed model is that iron rich nano-particles and nontronite dissolve in the intracellular acidic environment, leaving a residue of iron atoms at specific surface sites anchored to the windows of the zeolite channels. These sites may be active later as low nuclearity groups. PMID:27892512

Metal pollution loading, Manzalah lagoon, Nile delta, Egypt: Implications for aquaculture

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

Siegel, F.R.; Slaboda, M.L.; Stanley, D.J.

1994-03-01

High cultural enrichment factors are found for Hg (13 x), Pb (22.1 x), and other potentially toxic metals (e.g., Sn, Zn, Cu, Ag) in the upper 20 cm of sediment cores from the southeastern Ginka subbasin of Manzalah lagoon, Nile delta, Egypt. Cores from other areas of the lagoon show little metal loading. Metal loading followed the closure of the Aswan High Dam, the availability of abundant cheap electricity, and the development of major power-based industries. Industrial wastes containing potentially toxic metals are dumped into the Nile delta drain system. The load carried by Bahr El-Baqar drain discharges into themore » Ginka subbasin, which acts as a sink and results in metal loading of the sediment deposited there. Further development of aquaculture in this subbasin, of food-stuff agriculture on recently reclaimed lagoon bottom, or where irrigation waters come from Bahr El-Baqar drain or its discharge should be halted or strictly limited until potentially toxic metals in the drain waters and sediment are removed and polluted input drastically reduced. This environmental assessment of heavy metals in aquaculture or agriculture development should extend to other waterbodies in the northern Nile delta, particularly Idku lagoon and Lake Mariut, where industrial metal-bearing wastes discharge into the waterbodies. 21 refs., 7 figs., 3 tabs.« less

Tolerability of lomustine in combination with cyclophosphamide in dogs with lymphoma.

PubMed

Rassnick, Kenneth M; Bailey, Dennis B; Malone, Erin K; Flory, Andrea B; Kiselow, Michael A; Intile, Joanne L

2014-01-01

This retrospective study describes toxicity associated with a protocol of lomustine (CCNU) and cyclophosphamide (CTX) in dogs with lymphoma. CCNU was administered per os (PO) at a targeted dosage of 60 mg/m(2) body surface area on day 0, CTX was administered PO at a targeted dosage of 250 mg/m(2) divided over days 0 through 4, and all dogs received prophylactic antibiotics. Ninety treatments were given to the 57 dogs included in the study. Neutropenia was the principal toxic effect, and the overall frequency of grade 4 neutropenia after the first treatment of CCNU/CTX was 30% (95% confidence interval, 19-43%). The mean body weight of dogs with grade 4 neutropenia (19.7 kg ± 13.4 kg) was significantly less than the mean body weight of dogs that did not develop grade 4 neutropenia (31.7 kg ± 12.4 kg; P = .005). One dog (3%) developed hematologic changes suggestive of hepatotoxicity. No dogs had evidence of either renal toxicity or hemorrhagic cystitis. Adverse gastrointestinal effects were uncommon. On the basis of the findings reported herein, a dose of 60 mg/m(2) of CCNU combined with 250 mg/m(2) of CTX (divided over 5 days) q 4 wk is tolerable in tumor-bearing dogs.

Modeling sulfate reduction in methane hydrate-bearing continental margin sediments: Does a sulfate-methane transition require anaerobic oxidation of methane?

USGS Publications Warehouse

Malinverno, A.; Pohlman, J.W.

2011-01-01

The sulfate-methane transition (SMT), a biogeochemical zone where sulfate and methane are metabolized, is commonly observed at shallow depths (1-30 mbsf) in methane-bearing marine sediments. Two processes consume sulfate at and above the SMT, anaerobic oxidation of methane (AOM) and organoclastic sulfate reduction (OSR). Differentiating the relative contribution of each process is critical to estimate methane flux into the SMT, which, in turn, is necessary to predict deeper occurrences of gas hydrates in continental margin sediments. To evaluate the relative importance of these two sulfate reduction pathways, we developed a diagenetic model to compute the pore water concentrations of sulfate, methane, and dissolved inorganic carbon (DIC). By separately tracking DIC containing 12C and 13C, the model also computes ??13C-DIC values. The model reproduces common observations from methane-rich sediments: a well-defined SMT with no methane above and no sulfate below and a ??13C-DIC minimum at the SMT. The model also highlights the role of upward diffusing 13C-enriched DIC in contributing to the carbon isotope mass balance of DIC. A combination of OSR and AOM, each consuming similar amounts of sulfate, matches observations from Site U1325 (Integrated Ocean Drilling Program Expedition 311, northern Cascadia margin). Without AOM, methane diffuses above the SMT, which contradicts existing field data. The modeling results are generalized with a dimensional analysis to the range of SMT depths and sedimentation rates typical of continental margins. The modeling shows that AOM must be active to establish an SMT wherein methane is quantitatively consumed and the ??13C-DIC minimum occurs. The presence of an SMT generally requires active AOM. Copyright 2011 by the American Geophysical Union.

Highly Flexible Self-Assembled V2O5 Cathodes Enabled by Conducting Diblock Copolymers

NASA Astrophysics Data System (ADS)

An, Hyosung; Mike, Jared; Smith, Kendall; Swank, Lisa; Lin, Yen-Hao; Pesek, Stacy; Verduzco, Rafael; Lutkenhaus, Jodie

Structural energy storage materials combining load-bearing mechanical properties and high energy storage performance are desired for applications in wearable devices or flexible displays. Vanadium pentoxide (V2O5) is a promising cathode material for possible use in flexible battery electrodes, but it remains limited by low Li+ diffusion coefficient and electronic conductivity, severe volumetric changes upon cycling, and limited mechanical flexibility. Here, we demonstrate a route to address these challenges by blending a diblock copolymer bearing electron- and ion-conducting blocks, poly(3-hexylthiophene)-block-poly(ethyleneoxide) (P3HT- b-PEO), with V2O5 to form a mechanically flexible, electro-mechanically stable hybrid electrode. V2O5 layers were arranged parallel in brick-and-mortar-like fashion held together by the P3HT- b-PEO binder. This unique structure significantly enhances mechanical flexibility, toughness and cyclability without sacrificing capacity. Electrodes comprised of 10 wt% polymer have unusually high toughness (293 kJ/m3) and specific energy (530 Wh/kg), both higher than reduced graphene oxide paper electrodes.

Dripping and evolution behavior of primary slag bearing TiO2 through the coke packed bed in a blast-furnace hearth

NASA Astrophysics Data System (ADS)

Liu, Yan-xiang; Zhang, Jian-liang; Wang, Zhi-yu; Jiao, Ke-xin; Zhang, Guo-hua; Chou, Kuo-chih

2017-02-01

To investigate the flow of primary slag bearing TiO2 in the cohesive zone of blast furnaces, experiments were carried out based on the laboratory-scale packed bed systems. It is concluded that the initial temperature of slag dripping increases with decreasing FeO content and increasing TiO2 content. The slag holdup decreases when the FeO content is in the range of 5wt%-10wt%, whereas it increases when the FeO content exceeds 10wt%. Meanwhile, the slag holdup decreases when the TiO2 content increases from 5wt% to 10wt% but increases when the TiO2 content exceeds 10wt%. Moreover, slag/coke interface analysis shows that the reaction between FeO and TiO2 occurs between the slag and the coke. The slag/coke interface is divided into three layers: slag layer, iron-rich layer, and coke layer. TiO2 in the slag is reduced by carbon, and the generated Ti diffuses into iron.

Aerodynamically induced radial forces in a centrifugal gas compressor. Part 1: Experimental measurement

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

Moore, J.J.; Flathers, M.B.

1998-04-01

Net radial loading arising from asymmetric pressure fields in the volutes of centrifugal pumps during off-design operation is well known and has been studied extensively. In order to achieve a marked improvement in overall efficiency in centrifugal gas compressors, vaneless volute diffusers are matched to specific impellers to yield improved performance over a wide application envelope. As observed in centrifugal pumps, nonuniform pressure distributions that develop during operation above and below the design flow create static radial loads on the rotor. In order to characterize these radial forces, a novel experimental measurement and post-processing technique is employed that yields bothmore » the magnitude and direction of the load by measuring the shaft centerline locus in the tilt-pad bearings. The method is applicable to any turbomachinery operating on fluid film radial bearings equipped with proximity probes. The forces are found to be a maximum near surge and increase with higher pressures and speeds. The results are nondimensionalized, allowing the radial loading for different operating conditions to be predicted.« less

Prototype Development of Remote Operated Hot Uniaxial Press (ROHUP) to Fabricate Advanced Tc-99 Bearing Ceramic Waste Forms - 13381

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

Alaniz, Ariana J.; Delgado, Luc R.; Werbick, Brett M.

The objective of this senior student project is to design and build a prototype construction of a machine that simultaneously provides the proper pressure and temperature parameters to sinter ceramic powders in-situ to create pellets of rather high densities of above 90% (theoretical). This ROHUP (Remote Operated Hot Uniaxial Press) device is designed specifically to fabricate advanced ceramic Tc-99 bearing waste forms and therefore radiological barriers have been included in the system. The HUP features electronic control and feedback systems to set and monitor pressure, load, and temperature parameters. This device operates wirelessly via portable computer using Bluetooth{sup R} technology.more » The HUP device is designed to fit in a standard atmosphere controlled glove box to further allow sintering under inert conditions (e.g. under Ar, He, N{sub 2}). This will further allow utilizing this HUP for other potential applications, including radioactive samples, novel ceramic waste forms, advanced oxide fuels, air-sensitive samples, metallic systems, advanced powder metallurgy, diffusion experiments and more. (authors)« less

Isothermal reduction kinetics and mineral phase of chromium-bearing vanadium-titanium sinter reduced with CO gas at 873-1273 K

NASA Astrophysics Data System (ADS)

Yang, Song-tao; Zhou, Mi; Jiang, Tao; Xue, Xiang-xin

2018-02-01

Reduction of chromium-bearing vanadium-titanium sinter (CVTS) was studied under simulated conditions of a blast furnace, and thermodynamics and kinetics were theoretically analyzed. Reduction kinetics of CVTS at different temperatures was evaluated using a shrinking unreacted core model. The microstructure, mineral phase, and variation of the sinter during reduction were observed by X-ray diffraction, scanning electron microscopy, and metallographic microscopy. Results indicate that porosity of CVTS increased with temperature. Meanwhile, the reduction degree of the sinter improved with the reduction rate. Reduction of the sinter was controlled by a chemical reaction at the initial stage and inner diffusion at the final stage. Activation energies measured 29.22-99.69 kJ/mol. Phase transformations in CVTS reduction are as follows: Fe2O3→Fe3O4→FeO→Fe; Fe2TiO5→Fe2TiO4→FeTiO3; FeO·V2O3→V2O3; FeO·Cr2O3→Cr2O3.

Uranium content and leachable fraction of fluorspars

USGS Publications Warehouse

Landa, E.R.; Councell, T.B.

2000-01-01

Much attention in the radiological health community has recently focused on the management and regulation of naturally occurring radioactive materials. Although uranium-bearing minerals are present in a variety of fluorspar deposits, their potential consideration as naturally occurring radioactive materials has received only limited recognition. The uranium content of 28 samples of acid- and cryolite-grade (>97% CaF2) fluorspar from the National Defense Stockpile was found to range from 120 to 24,200 ??g kg-1, with a mean of 2,145 ??g kg-1. As a point of comparison, the average concentration of uranium in the upper crust of the earth is about 2,500 ??g kg-1. Leachability of this uranium was assessed by means of the Toxicity Characteristic Leaching Procedure (TCLP). The TCLP extractable fraction ranged from 1 to 98%, with a mean of 24% of the total uranium. The typically low concentrations of uranium seen in these materials probably reflects the removal of uranium-bearing mineral phases during the beneficiation of the crude fluorspar ore to achieve industrial specifications. Future NORM studies should examine crude fluorspar ores and flotation tailings.

Investigation of Lysine-Functionalized Dendrimers as Dichlorvos Detoxification Agents.

PubMed

Durán-Lara, Esteban F; Marple, Jennifer L; Giesen, Joseph A; Fang, Yunlan; Jordan, Jacobs H; Godbey, W Terrence; Marican, Adolfo; Santos, Leonardo S; Grayson, Scott M

2015-11-09

Lysine-containing polymers have seen broad application due to their amines' inherent ability to bind to a range of biologically relevant molecules. The synthesis of multiple generations of polyester dendrimers bearing lysine groups on their periphery is described in this report. Their hydrolytic stabilities with respect to pH and time, their toxicity to a range of cell lines, and their possible application as nano-detoxification agents of organophosphate compounds are all investigated. These zeroth-, first-, and second-generation water-soluble dendrimers have been designed to bear exactly 4, 8, and 16 lysine groups, respectively, on their dendritic periphery. Such monodisperse bioactive polymers show potential for a range of applications including drug delivery, gene delivery, heavy metal binding, and the sequestration of organic toxins. These monodisperse bioactive dendrimers were synthesized using an aliphatic ester dendritic core (prepared from pentaerythritol) and protected amino acid moieties. This library of lysine-conjugated dendrimers showed the ability to efficiently capture the pesticide dichlorvos, confirming the potential of dendrimer-based antidotes to maintain acetylcholinesterase activity in response to poisoning events.

Synthesis and bioactivities of halogen bearing phenolic chalcones and their corresponding bis Mannich bases.

PubMed

Yamali, Cem; Gul, Halise Inci; Sakagami, Hiroshi; Supuran, Claudiu T

2016-01-01

Phenolic bis Mannich bases having the chemical structure of 1-[3,5-bis-aminomethyl-4-hydroxyphenyl]-3-(4-halogenophenyl)-2-propen-1-ones (1a-c, 2a-c, 3a-c) were synthesized (Numbers 1, 2, and 3 represent fluorine, chlorine, and bromine bearing compounds, respectively, while a, b, and c letters represent the compounds having piperidine, morpholine, and N-methyl piperazine) and their cytotoxic and carbonic anhydrase (CA, EC 4.2.1.1) enzyme inhibitory effects were evaluated. Lead compounds should possess both marked cytotoxic potencies and selective toxicity for tumors. To reflect this potency, PSE values of the compounds were calculated. According to PSE values, the compounds 2b and 3b may serve as lead molecules for further anticancer drug candidate developments. Although the compounds showed a low inhibition potency toward hCA I (25-43%) and hCA II (6-25%) isoforms at 10 μM concentration of inhibitor, the compounds were more selective (1.5-5.2 times) toward hCA I isoenzyme. It seems that the compounds need molecular modifications for the development of better CA inhibitors.

Tumor regression after intravenous administration of targeted vesicles entrapping the vitamin E α-tocotrienol.

PubMed

Karim, Reatul; Somani, Sukrut; Al Robaian, Majed; Mullin, Margaret; Amor, Rumelo; McConnell, Gail; Dufès, Christine

2017-01-28

The therapeutic potential of tocotrienol, a member of the vitamin E family of compounds with potent in vitro anti-cancer properties, is limited by its inability to specifically reach tumors following intravenous administration. The purpose of this study is to determine whether a novel tumor-targeted vesicular formulation of tocotrienol would suppress the growth of A431 epidermoid carcinoma and B16-F10 melanoma in vitro and in vivo. In this work, we demonstrated that novel transferrin-bearing multilamellar vesicles entrapping α-T3 resulted in a dramatically improved (by at least 52-fold) therapeutic efficacy in vitro on A431 cell line, compared to the free drug. In addition, the intravenous administration of tocotrienol entrapped in transferrin-bearing vesicles resulted in tumor suppression for 30% of A431 and 60% of B16-F10 tumors, without visible toxicity. Mouse survival was enhanced by >13days compared to controls administered with the drug solution only. This tumor-targeted, tocotrienol-based nanomedicine therefore significantly improved the therapeutic response in cancer treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Geochemical Weathering Increases Lead Bioaccessibility in Semi-Arid Mine Tailings

PubMed Central

Hayes, Sarah M.; Webb, Sam M.; Bargar, John R.; O'Day, Peggy A.; Maier, Raina M.; Chorover, Jon

2012-01-01

Mine tailings can host elevated concentrations of toxic metal(loid)s that represent a significant hazard to surrounding communities and ecosystems. Eolian transport, capable of translocating small (micrometer-sized) particles, can be the dominant mechanism of toxic metal dispersion in arid or semi-arid landscapes. Human exposure to metals can then occur via direct inhalation or ingestion of particulates. The fact that measured doses of total lead (Pb) in geomedia correlate poorly with blood Pb levels highlights a need to better resolve the precise distribution of molecularly-speciated metal-bearing phases in the complex particle mixtures. Species distribution controls bioaccessibility, thereby directly impacting health risk. This study seeks to correlate Pb-containing particle size and mineral composition with lability and bioaccessibility in mine tailings subjected to weathering in a semi-arid environment. We employed X-ray absorption spectroscopy (XAS) and X-ray fluorescence (XRF), coupled with sequential chemical extractions, to study Pb speciation in tailings from the semi-arid Arizona Klondyke State Superfund Site. Representative samples ranging in pH from 2.6 to 5.4 were selected for in-depth study of Pb solid-phase speciation. The principle lead-bearing phase was plumbojarosite (PbFe6(SO4)4(OH)12), but anglesite (PbSO4) and iron oxide-sorbed Pb were also observed. Anglesite, the most bioavailable mineral species of lead identified in this study, was enriched in surficial tailings samples, where Pb concentrations in the clay size fraction were 2–3 times higher by mass relative to bulk. A mobile and bioaccessible Pb phase accumulates in surficial tailings, with a corresponding increase in risk of human exposure to atmospheric particles. PMID:22553941

The molecular chemistry of diffuse and translucent clouds in the line-of-sight to Sgr B2: Absorption by simple organic and inorganic molecules in the GBT PRIMOS survey

NASA Astrophysics Data System (ADS)

Corby, J. F.; McGuire, B. A.; Herbst, E.; Remijan, A. J.

2018-02-01

The 1-50 GHz PRebiotic Interstellar MOlecular Survey (PRIMOS) contains 50 molecular absorption lines observed in clouds located in the line-of-sight to Sgr B2(N). The line-of-sight material is associated with diffuse and translucent clouds located in the Galactic center, bar, and spiral arms in the disk. We measured the column densities and estimate abundances, relative to H2, of 11 molecules and additional isotopologues observed in this material. We used absorption by optically thin transitions of c-C3H2 to estimate the molecular hydrogen columns, and argue that this method is preferable to more commonly used methods. We discuss the kinematic structure and abundance patterns of small molecules including the sulfur-bearing species CS, SO, CCS, H2CS, and HCS+; oxygen-bearing molecules OH, SiO, and H2CO; and simple hydrocarbon molecules c-C3H2, l-C3H, and l-C3H+. Finally, we discuss the implications of the observed chemistry for the structure of the gas and dust in the ISM. Highlighted results include the following. First, whereas gas in the disk has a molecular hydrogen fraction of 0.65, clouds on the outer edge of the Galactic bar and in or near the Galactic center have molecular fractions of 0.85 and >0.9, respectively. Second, we observe trends in isotope ratios with Galactocentric distance; while carbon and silicon show enhancement of the rare isotopes at low Galactocentric distances, sulfur exhibits no trend with Galactocentric distance. We also determine that the ratio of c-C3H2/c-H13CCCH provides a good estimate of the 12C/13C ratio, whereas H2CO/H213CO exhibits fractionation. Third, we report the presence of l-C3H+ in diffuse clouds for the first time. Finally, we suggest that CS has an enhanced abundance within higher density clumps of material in the disk, and therefore may be diagnostic of cloud conditions. If this holds, the diffuse clouds in the Galactic disk contain multiple embedded hyperdensities in a clumpy structure, and the density profile is not a simple function of AV. The reduced spectra (FITS files) are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/610/A10

Microstructural characteristics of HIP-bonded monolithic nuclear fuels with a diffusion barrier

NASA Astrophysics Data System (ADS)

Jue, Jan-Fong; Keiser, Dennis D.; Breckenridge, Cynthia R.; Moore, Glenn A.; Meyer, Mitchell K.

2014-05-01

Due to the limitation of maximum uranium load achievable by dispersion fuel type, the Global Threat Reduction Initiative is developing an advanced monolithic fuel to convert US high-performance research reactors to low-enriched uranium. Hot-isostatic-press (HIP) bonding was the single process down-selected to bond monolithic U-Mo fuel meat to aluminum alloy cladding. A diffusion barrier was applied to the U-Mo fuel meat by roll-bonding process to prevent extensive interaction between fuel meat and aluminum-alloy cladding. Microstructural characterization was performed on fresh fuel plates fabricated at Idaho National Laboratory. Interfaces between the fuel meat, the cladding, and the diffusion barrier, as well as between the U-10Mo fuel meat and the Al-6061 cladding, were characterized by scanning electron microscopy. Preliminary results indicate that the interfaces contain many different phases while decomposition, second phases, and chemical banding were also observed in the fuel meat. The important attributes of the HIP-bonded monolithic fuel are:

Structure, thermodynamics, and properties of hydrous aluminosilicate melt in the deep Earth

NASA Astrophysics Data System (ADS)

Bajgain, S. K.; Mookherjee, M.

2017-12-01

In this study, we use first-principles molecular dynamics (FPMD) simulations to explore the structure, thermodynamics, and transport properties of alkali bearing aluminosliciate melt (NaAlSi2O6) with 4 wt.% H2O. We explored physical properties of the hydrous jadeite melt at temperatures and pressures relevant for the Earth's mantle, i.e., 2500- 4000 K and up to 50 GPa. Our results indicate that the fundamental structural units of jadeite, i.e., one dimensional (1-D) chain with a repeat of [Si2O6]4- is well preserved in anhydrous jadeite melt at low pressures. However, the 1-D chains are nonlinear and the silicate tetrahedral units are very distorted. We also note that in the hydrous jadeite melt, the dominant hydrogen bearing species are hydroxyl (OH) and water molecules (H2O). We do not find any evidence of OH attached to the bridging oxygen atoms. However, we do find OH groups attached to the non-bridging oxygen atoms at the terminal sites of the tetrahedral units associated with the distorted 1-D chains. It is possible that these terminal OH groups were former bridging oxygen atoms. Pressure-volume-temperature results of hydrous jadeite melt could be adequately described with a finite-strain equation of state with ρ0, K0, and K'0 being 2.0 g/cm3, 13.0 GPa, and 4.0, respectively. Our FPMD results also indicate that the diffusivity of alkali (Na) ions is comparable to the hydrogen atoms at lower pressures ( 90 ×10-10 m2/s at 6 GPa and 2500 K). The self diffusion of aluminum (6.5 ×10-10 m2/s) and silicon (4.5 ×10-10 m2/s) ions are significantly lower compared to the alkali ions and proton at the similar P-T condition. At higher pressures i.e., P> 20 GPa, the diffusivity of Na reduces significantly. At P> 20 GPa, the proton diffusivity remains higher than the other cation species. Therefore, a small fraction of hydrous melt at mantle transition zone conditions may explain the observed elevated electrical conductivity in specific regions such as in Japan and in the Northeastern China [1]. Acknowledgment: This work is supported by US NSF award EAR 1639552. Reference: [1] Kelbert et al., 2009, Global electromagnetic induction constraints on transition-zone water content variations, Nature, 460, 103-107.

Microstructural Characteristics of HIP-bonded Monolithic Nuclear Fuels with a Diffusion Barrier

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

Jan-Fong Jue; Dennis D. Keiser, Jr.; Cynthia R. Breckenridge

Due to the limitation of maximum uranium load achievable by dispersion fuel type, the Global Threat Reduction Initiative (GTRI) is developing an advanced monolithic fuel to convert US high performance research reactors to low-enriched uranium. Hot-isostatic-press bonding was the single process down-selected to bond monolithic U-Mo fuel meat to aluminum alloy cladding. A diffusion barrier was applied to the U–Mo fuel meat by roll-bonding process to prevent extensive interaction between fuel meat and aluminum-alloy cladding. Microstructural characterization was performed on fresh fuel plates fabricated at Idaho National Laboratory. Interfaces between fuel meat, cladding, and diffusion barrier, as well as U–10Momore » fuel meat and Al–6061 cladding were characterized by scanning electron microscopy. Preliminary results indicate that the interfaces contain many different phases while decomposition, second phases, and chemical banding were also observed in the fuel meat. The important attributes of the HIP-bonded monolithic fuel are • A typical Zr diffusion barrier of thickness 25 µm • Transverse cross section that exhibits relatively equiaxed grains with an average grain diameter of 10 µm • Chemical banding, in some areas more than 100 µm in length, that is very pronounced in longitudinal (i.e., rolling) direction with Mo concentration varying from 7–13 wt% • Decomposed areas containing plate-shaped low-Mo phase • A typical Zr/cladding interaction layer of thickness 1-2 µm • A visible UZr2 bearing layer of thickness 1-2 µm • Mo-rich precipitates (mainly Mo2Zr, forming a layer in some areas) followed by a Mo-depleted sub-layer between the visible UZr2-bearing layer and the U–Mo matrix • No excessive interaction between cladding and the uncoated fuel edge • Cladding-to-cladding bonding that exhibits no cracks or porosity with second phases high in Mg, Si, and O decorating the bond line. • Some of these attributes might be critical to the irradiation performance of monolithic U-10Mo nuclear fuel. There are several issues or concerns that warrant more detailed study, such as precipitation along cladding-to-cladding bond line, chemical banding, uncovered fuel-zone edge, and interaction layer between U–Mo fuel meat and zirconium. Future post-irradiation examination results will focus, among other things, on identifying in-reactor failure mechanisms and, eventually, directing further fresh fuel characterization efforts.« less

Direct comparison of two pegylated liposomal doxorubicin formulations: is AUC predictive for toxicity and efficacy?

PubMed

Cui, Jingxia; Li, Chunlei; Guo, Wenmin; Li, Yanhui; Wang, Caixia; Zhang, Li; Zhang, Lan; Hao, Yanli; Wang, Yongli

2007-04-02

Rationally designed liposomes could improve the therapeutic indexes of chemotherapeutic drugs, which is due to alterations in the pharmacokinetics and biodistribution of encapsulated drugs. For traditional drug delivery systems, the accumulation of drugs in healthy and malignant tissues could be correlated with toxicity and efficacy. Some previous studies also indicate that the higher tumor AUC, the better therapeutic efficacy, suggestive of the possible existence of positive correlation. Are AUC values of liposomal drugs really predictive? For the purpose to address this question, we designed two pegylated liposomal doxorubicin formulations (PLD-75 and PLD-100), which had the same lipid/drug ratio and bilayer composition, but different size and internal ammonium sulfate concentration. In vitro drug retention experiments revealed that drug was released at a faster rate from PLD-75, a small size formulation. The plasma pharmacokinetics of PLD-75 was similar to that of PLD-100, regardless of whether the mice were tumor-free or not. It should be noted, though, that in tumor-bearing mice the plasma doxorubicin level in PLD-75 group was only about 59% of that in PLD-100 group at 48 h post injection. Furthermore, their biodistribution behavior in S-180 tumor-bearing KM mice was significantly different. Compared with animals receiving PLD-100, those receiving PLD-75 showed a 19.2%, 27.8%, and 23.5% decrease in liver (p<0.01), spleen (p<0.001) and lung (p<0.05) AUC, respectively. In other healthy tissues except kidney, the drug deposition also reduced by 10-15%, but the difference was not significant. The tumor AUC after administration of PLD-100 and PLD-75 were 1285.3 ugh/g and 762.0 ugh/g, respectively (p<0.001). Maximum drug levels achieved in the tumors were 33.80 microg/g (for PLD-100) and 20.85 microg/g (for PLD-75), and peak tumor concentration was achieved faster in PLD-75 group. However, enhanced drug accumulation does not mean increased antineoplastic effect, and at the same doxorubicin dose level, PLD-75 was more efficacious. As for toxicity studies, PLD-75 caused more rapid and severe body weight loss despite the fact that drug accumulation in healthy tissues was reduced. Our data indicate that liposomal systems are more complicated than conventional drug delivery systems, and it is hard to predict the toxicity and efficacy of liposomal drugs through the measure of liposomal drug accumulation.

Pulsed and oscillating gradient MRI for assessment of cell size and Extracellular space (POMACE) in mouse gliomas

PubMed Central

Reynaud, Olivier; Winters, Kerryanne Veronica; Hoang, Dung Minh; Wadghiri, Youssef Zaim; Novikov, Dmitry S.; Kim, Sungheon Gene

2016-01-01

Solid tumor microstructure is related to aggressiveness of tumor, interstitial pressure and drug delivery pathways that are closely associated with treatment response, metastatic spread and prognosis. In this study, we introduce a novel diffusion MRI data analysis framework, Pulsed and Oscillating gradient MRI for Assessment of Cell size and Extracellular space (POMACE), and demonstrate its feasibility in a mouse tumor model. In vivo and ex vivo POMACE experiments were performed on mice bearing the GL261 murine glioma model (n=8). Since the complete diffusion time-dependence is in general non-analytical, the tumor microstructure was modeled in an appropriate time/frequency regime by impermeable spheres (radius Rcell, intracellular diffusivity Dics) surrounded by extracellular space (approximated by constant apparent diffusivity Decs in volume fraction ECS). POMACE parametric maps (ECS, Rcell, Dics, Decs) were compared with conventional diffusion weighted imaging metrics, electron microscopy (EM), alternative ECS determination based on effective medium theory (EMT), and optical microscopy performed on the same samples. It was shown that Decs can be approximated by its long-time tortuosity limit in the range [1/(88 Hz) - 31 ms]. ECS estimations (44±7% in vivo and 54±11% ex vivo) were in agreement with EMT-based ECS and literature on brain gliomas. Ex vivo, ECS maps correlated well with optical microscopy. Cell sizes (Rcell=4.8±1.3 in vivo and 4.3±1.4 μm ex vivo) were consistent with EM measurements (4.7±1.8 μm). In conclusion, Rcell and ECS can be quantified and mapped in vivo and ex vivo in brain tumors using the proposed POMACE method. Our experimental results support that POMACE provides a way to interpret the frequency- or time-dependence of the diffusion coefficient in tumors in terms of objective biophysical parameters of neuronal tissue, which can be used for non-invasive monitoring of preclinical cancer studies and treatment efficacy. PMID:27448059

Timescales between mantle metasomatism and kimberlite ascent indicated by diffusion profiles in garnet crystals from peridotite xenoliths

NASA Astrophysics Data System (ADS)

Jollands, Michael C.; Hanger, Brendan J.; Yaxley, Gregory M.; Hermann, Jörg; Kilburn, Matthew R.

2018-01-01

Rare garnet crystals from a peridotite xenolith from the Wesselton kimberlite, South Africa, have distinct zones related to two separate episodes of mantle metasomatism. The garnet cores were firstly depleted through melt extraction, then equilibrated during metasomatism by a potentially diamond-forming carbonate-bearing or proto-kimberlitic fluid at 1100-1300 °C and 4.5-5.5 GPa. The garnet rim chemistry, in contrast, is consistent with later overgrowth in equilibrium with a kimberlite at around 1025 ± 25 °C and 4.2 ± 0.5 GPa. This suggests that the rock was physically moved upwards by up to tens of kilometres between the two metasomatic episodes. Preserved high Ca, Al and Cr contents in orthopyroxenes suggest this uplift was tectonic, rather than magmatic. Diffusion profiles were measured over the transitions between garnet cores and rims using electron microprobe (Mg, Ca, Fe for modelling, plus Cr, Mn, Ti, Na, Al) and nano Secondary Ion Mass Spectrometry (NanoSIMS; 89Y, along with 23Na, Ca, Cr, Fe, Mn and Ti) analyses. The short profile lengths (generally <10 μm) and low Y concentrations (0.2-60 ppm) make the NanoSIMS approach preferable. Diffusion profiles at the interface between the zones yield constraints on the timescale between the second metasomatic event and eruption of the kimberlite magma that brought the xenolith to the surface. The time taken to form the diffusion profiles is on the order of 25 days to 400 yr, primarily based on modelling of Y diffusion along with Ca, Fe and Mg (multicomponent diffusion) profiles. These timescales are too long to be produced by the interaction of the mantle xenolith with the host kimberlite magma during a single-stage ascent to the crust (hours to days). The samples offer a rare opportunity to study metasomatic processes associated with failed eruption attempts in the cratonic lithosphere.

Diffusion of Water through Olivine and Clinopyroxene: Implications for Melt Inclusion Fidelity

NASA Astrophysics Data System (ADS)

Plank, T. A.; Lloyd, A. S.; Ferriss, E.

2016-12-01

The maximum H2O concentrations measured in olivine-hosted melt inclusions (MIs) from arc tephra fall within a narrow range of 3-5 wt%. A major question is whether this reflects parental water concentrations or diffusive exchange through the host crystal during storage and ascent. Laboratory experiments have shown that water can diffuse through 500 micron olivine in minutes to days at 1100°C. We have tested these predictions with a natural experiment using volatile (H2O, CO2, S) diffusion along melt embayments to constrain ascent rates during the 1974 eruption of Volcan Fuego to 5-8 minutes from 7 km depth [1]. Thus, olivine-hosted MIs may move from their storage region to the surface during some eruptions rapidly enough to retain almost all of their original water. Only the smallest MIs (< 30 microns) will lose any water during such fast ascent, even for the fastest diffusion mechanism through olivine. We have also assessed the potential for clinopyroxene (cpx) to retain water (as H+) during magma ascent. In the same 1974 Fuego deposits, cpx crystals show H-loss on their rims and even from their interiors. Such diffusive loss in 5-8 minutes requires rapid diffusion of H in cpx, comparable to olivine and melt, and consistent with our recent laboratory experiments dehydrating Fe-bearing cpx [2]. Although H-diffusion is dependent on the site occupancy, all sites may lose H rapidly in cpx with Mg# < 92.5. While cpx and olivine may lose H during ascent and degassing, olivine-hosted MIs stand a better chance of retaining water due to the very low partitioning of water in olivine (D 0.001). The most favorable conditions for faithful retention of parental water concentrations involve a) rapid ascent (< hr.) from H2O-undersaturated reservoirs (prior to major water degassing), b) minerals with low partition coefficients for water, c) large crystals (>500 microns) and large melt inclusions (>50 microns), and 4) rapid post-eruptive cooling (< 1min, clast sizes < 1 cm). The rapid diffusion of H through olivine and cpx presents a challenge to MI fidelity, but not necessarily if the above conditions are met. [1] Lloyd et al., 2014, JVGR. [2] Ferriss et al., 2016, AmMin.

Ionic liquids toxicity on fresh water microalgae, Scenedesmus quadricauda, Chlorella vulgaris &Botryococcus braunii; selection criterion for use in a two-phase partitioning bioreactor (TPPBR).

PubMed

Quraishi, Khurrum Shehzad; Bustam, Mohamad Azmi; Krishnan, Sooridarsan; Aminuddin, Noor Fathanah; Azeezah, Noraisyah; Ghani, Noraini Abd; Uemura, Yoshimitsu; Lévêque, Jean Marc

2017-10-01

A promising method of Carbon dioxide (CO 2 ) valorization is to use green microalgae photosynthesis to process biofuel. Two Phase Partitioning Bioreactors (TPPBR) offer the possibility to use non-aqueous phase liquids (NAPL) to enhance CO 2 solubility; thus making CO 2 available to maximize algae growth. This requires relatively less toxic hydrophobic Ionic Liquids (ILs) that comprise a new class of ionic compounds with remarkable physicochemical properties and thus qualifies them as NAPL candidates. This paper concerns the synthesis of ILs with octyl and butyl chains as well as different cations containing aromatic (imidazolium, pyridinium) and non-aromatic (piperidinum, pyrrolidinium) rings for CO 2 absorption studies. The authors measured their respective toxicity levels on microalgae species, specifically, Scenedesmus quadricauda, Chlorella vulgaris and Botryococcus braunii. Results revealed that octyl-based ILs were more toxic than butyl-based analogues. Such was the case for bmim-PF6 at double saturation with an absorbance of 0.11, compared to Omim-PF6 at 0.17, bmim-NTf2 at 0.02, and Omim-NTf2 at 0.14, respectively. CO 2 uptake results for ILs bearing octyl-based chains compared to the butyl analog were 54% (nCO 2 /nIL) (i.e., moles of CO 2 moles of IL) and 38% (nCO 2 /nIL), respectively. Conclusively, 1-butyl-1-methylpiperidinium absorbed 13% (nCO 2 /nIL) and appeared the least toxic, having an absorbance of 0.25 at 688 nm (double saturation at 7 d) compared to 1-butyl-3-methylimidazolium, which showed the highest toxicity with zero absorbance. Accordingly, these findings suggest that 1-butyl-1-methylpiperidinium is capable of transporting CO 2 to a system containing green microalgae without causing significant harm; thus allowing its use in TPPBR technology. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

Chance, William W.; Rice, David C.; Allen, Pamela K.

Purpose: To investigate safety, efficacy, and recurrence after hemithoracic intensity modulated radiation therapy after pleurectomy/decortication (PD-IMRT) and after extrapleural pneumonectomy (EPP-IMRT). Methods and Materials: In 2009-2013, 24 patients with mesothelioma underwent PD-IMRT to the involved hemithorax to a dose of 45 Gy, with an optional integrated boost; 22 also received chemotherapy. Toxicity was scored with the Common Terminology Criteria for Adverse Events v4.0. Pulmonary function was compared at baseline, after surgery, and after IMRT. Kaplan-Meier analysis was used to calculate overall survival (OS), progression-free survival (PFS), time to locoregional failure, and time to distant metastasis. Failures were in-field, marginal, or outmore » of field. Outcomes were compared with those of 24 patients, matched for age, nodal status, performance status, and chemotherapy, who had received EPP-IMRT. Results: Median follow-up time was 12.2 months. Grade 3 toxicity rates were 8% skin and 8% pulmonary. Pulmonary function declined from baseline to after surgery (by 21% for forced vital capacity, 16% for forced expiratory volume in 1 second, and 19% for lung diffusion of carbon monoxide [P for all = .01]) and declined still further after IMRT (by 31% for forced vital capacity [P=.02], 25% for forced expiratory volume in 1 second [P=.01], and 30% for lung diffusion of carbon monoxide [P=.01]). The OS and PFS rates were 76% and 67%, respectively, at 1 year and 56% and 34% at 2 years. Median OS (28.4 vs 14.2 months, P=.04) and median PFS (16.4 vs 8.2 months, P=.01) favored PD-IMRT versus EPP-IMRT. No differences were found in grade 4-5 toxicity (0 of 24 vs 3 of 24, P=.23), median time to locoregional failure (18.7 months vs not reached, P not calculable), or median time to distant metastasis (18.8 vs 11.8 months, P=.12). Conclusions: Hemithoracic intensity modulated radiation therapy after pleurectomy/decortication produced little high-grade toxicity but led to progressive declines in pulmonary function; OS and PFS were better in PD-IMRT compared with EPP-IMRT.« less

Diffuse gas emissions at the Ukinrek Maars, Alaska: Implications for magmatic degassing and volcanic monitoring

USGS Publications Warehouse

Evans, William C.; Bergfeld, D.; McGimsey, R.G.; Hunt, A.G.

2009-01-01

Diffuse CO2 efflux near the Ukinrek Maars, two small volcanic craters that formed in 1977 in a remote part of the Alaska Peninsula, was investigated using accumulation chamber measurements. High CO2 efflux, in many places exceeding 1000 g m-2 d-1, was found in conspicuous zones of plant damage or kill that cover 30,000-50,000 m2 in area. Total diffuse CO2 emission was estimated at 21-44 t d-1. Gas vents 3-km away at The Gas Rocks produce 0.5 t d-1 of CO2 that probably derives from the Ukinrek Maars basalt based on similar ??13C values (???-6???), 3He/4He ratios (5.9-7.2 RA), and CO2/3He ratios (1-2 ?? 109) in the two areas. A lower 3He/4He ratio (2.7 RA) and much higher CO2/3He ratio (9 ?? 1010) in gas from the nearest arc-front volcanic center (Mount Peulik/Ugashik) provide a useful comparison. The large diffuse CO2 emission at Ukinrek has important implications for magmatic degassing, subsurface gas transport, and local toxicity hazards. Gas-water-rock interactions play a major role in the location, magnitude and chemistry of the emissions.

Performance of a passive direct ethanol fuel cell

NASA Astrophysics Data System (ADS)

Pereira, J. P.; Falcão, D. S.; Oliveira, V. B.; Pinto, A. M. F. R.

2014-06-01

Ethanol emerges as an attractive fuel since it is less toxic and has higher energy density than methanol and can be produced from biomass. Direct ethanol fuel cells (DEFCs) appear as a good choice for producing sustainable energy for portable applications. However, they are still far from attaining acceptable levels of power output, since their performance is affected by the slow electrochemical ethanol oxidation and water and ethanol crossover. In the present work, an experimental study on the performance of a passive DEFC is described. Tailored MEAs (membrane electrode assembly) with different catalyst loadings, anode diffusion layers and membranes were tested in order to select optimal working conditions at high ethanol concentrations and low ethanol crossover. The performance increased with an increase of membrane and anode diffusion layer thicknesses and anode catalyst loading. A maximum power density of 1.33 mW cm-2, was obtained using a Nafion 117 membrane, 4 mg cm-2 of Pt-Ru and 2 mg cm-2 of Pt on the anode and cathode catalyst layers, ELAT as anode diffusion layer, carbon cloth as cathode diffusion layer and an ethanol concentration of 2 M. As far as the authors are aware this is the first work reporting an experimental optimization of passive DEFCs.

Kinetic modeling of copper biosorption by immobilized biomass

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

Veglio, F.; Beolchini, F.; Toro, L.

1998-03-01

Biosorption of heavy metals is one of the most promising technologies involved in the removal of toxic metals from industrial waste streams and natural waters. The kinetic modeling of copper biosorption by Arthrobacter sp. immobilized in a hydroxyethyl methacrylate-based matrix is reported in this work. The resin-biomass complex (RBC) has been used for copper biosorption in different conditions according to a factorial experiment. Factors investigated were cross-linker (trimethylolpropane trimethacrylate) concentration, biomass concentration in the solid, and particles` granulometry. A maximum copper specific uptake of abut 7 mg of Cu/g of biomass (dry weight) has been observed, in the case ofmore » a RBC with the following characteristics: 2% (w/w) cross-linker concentration, 8% (w/w) biomass concentration, and 425--750 {micro}m granulometry. The shrinking core model has been used for the fitting of experimental data. A good fit has been found in the case of controlling intraparticle diffusion in all experimental trials. The copper diffusion coefficient in RBC has been estimated from the slope of the regression lines. Values obtained for the diffusion coefficients do not differ from one another with respect to the estimated standard error. An average apparent copper diffusion coefficient of about 3 {times} 10{sup {minus}6} cm{sup 2}/s has been found.« less

Cellular toxicity of TiO2-based nanofilaments.

PubMed

Magrez, Arnaud; Horváth, Lenke; Smajda, Rita; Salicio, Valérie; Pasquier, Nathalie; Forró, László; Schwaller, Beat

2009-08-25

At present, nanofilaments are not exclusively based on carbon atoms but can be produced from many inorganic materials in the form of nanotubes and nanowires. It is essential to systematically assess the acute toxicity of these newly synthesized materials since it cannot be predicted from the known toxicity of the same material in another form. Here, the cellular toxicity of TiO2-based nanofilaments was studied in relation to their morphology and surface chemistry. These structures produced by hydrothermal treatment were titanate nanotubes and nanowires with a Na(x)TiO(2+delta) composition. The cytotoxic effect was mainly evaluated by MTT assays combined with direct cell counting and cytopathological analyses of the lung tumor cells. Our work clearly demonstrated that the presence of Na(x)TiO(2+delta) nanofilaments had a strong dose-dependent effect on cell proliferation and cell death. Nanofilament internalization and alterations in cell morphology were observed. Acid treatment performed to substitute Na(+) with H(+) in the Na(x)TiO(2+delta) nanofilaments strongly enhanced the cytotoxic action. This effect was attributed to structural imperfections, which are left by the atom diffusion during the substitution. On the basis of our findings, we conclude that TiO2-based nanofilaments are cytotoxic and thus precautions should be taken during their manipulation.

Towards a Molecular Understanding of the Antibacterial Mechanism of Copper-bearing Titanium Alloys against Staphylococcus aureus

PubMed Central

Li, Mei; Ma, Zheng; Zhu, Ye; Xia, Hong; Yao, Mengyu; Chu, Xiao; Wang, Xiaolan; Yang, Ke

2016-01-01

The antibacterial mechanism of the Cu-containing materials has not been fully understood although such understanding is crucial for the sustained clinical use of Cu-containing antibacterial materials such as bone implants. The aim of this study is to investigate the molecular mechanisms by which the Gram-positive Staphylococcus aureus (S.aureus) is inactivated through Cu-bearing titanium alloys (Ti6Al4V5Cu). Cu ions released from the alloys were found to contribute to lethal damage of bacteria. They destroyed the permeability of the bacterial membranes, resulting in the leakage of reducing sugars and proteins from the cells. They also promoted the generation of bacteria-killing reactive oxygen species (ROS). The ROS production was confirmed by several assays including fluorescent staining of intracellular oxidative stress, detection of respiratory chain activity, and measurement of the levels of lipid peroxidation, catalase and glutathione. Furthermore, the released Cu ions showed obvious genetic toxicity by interfering the replication of nuc (species-specific) and 16SrRNA genes, but with no effect on the genome integrity. All of these effects lead to the antibacterial effect of Ti6Al4V5Cu. Collectively, our work reconciles the conflicting antibacterial mechanisms of Cu-bearing metallic materials or nanoparticles reported in the literature, as well as highlight the potential use of Ti6Al4V5Cu alloys in inhibiting bacterial infections. PMID:26692564

Heap leach cyanide irrigation and risk to wildlife: Ramifications for the international cyanide management code.

PubMed

Donato, D B; Madden-Hallett, D M; Smith, G B; Gursansky, W

2017-06-01

Exposed cyanide-bearing solutions associated with gold and silver recovery processes in the mining industry pose a risk to wildlife that interact with these solutions. This has been documented with cyanide-bearing tailings storage facilities, however risks associated with heap leach facilities are poorly documented, monitored and audited. Gold and silver leaching heap leach facilities use cyanide, pH-stabilised, at concentrations deemed toxic to wildlife. Their design and management are known to result in exposed cyanide-bearing solutions that are accessible to and present a risk to wildlife. Monitoring of the presence of exposed solutions, wildlife interaction, interpretation of risks and associated wildlife deaths are poorly documented. This paper provides a list of critical monitoring criteria and attempts to predict wildlife guilds most at risk. Understanding the significance of risks to wildlife from exposed cyanide solutions is complex, involving seasonality, relative position of ponding, temporal nature of ponding, solution palatability, environmental conditions, in situ wildlife species inventory and provision of alternative drinking sources for wildlife. Although a number of heap leach operations are certified as complaint with the International Cyanide Management Code (Cyanide Code), these criteria are not considered by auditors nor has systematic monitoring regime data been published. Without systematic monitoring and further knowledge, wildlife deaths on heap leach facilities are likely to remain largely unrecorded. This has ramifications for those operations certified as compliance with the Cyanide Code. Copyright © 2017 Elsevier Inc. All rights reserved.

Glass Development for Treatment of LANL Evaporator Bottoms Waste

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

DE Smith; GF Piepel; GW Veazey

1998-11-20

Vitrification is an attractive treatment option for meeting the stabilization and final disposal requirements of many plutonium (Pu) bearing materials and wastes at the Los Alamos National Laboratory (LANL) TA-55 facility, Rocky Flats Environmental Technology Site (RFETS), Hanford, and other Department of Energy (DOE) sites. The Environmental Protection Agency (EPA) has declared that vitrification is the "best demonstrated available technology" for high- level radioactive wastes (HLW) (Federal Register 1990) and has produced a handbook of vitriilcation technologies for treatment of hazardous and radioactive waste (US EPA, 1992). This technology has been demonstrated to convert Pu-containing materials (Kormanos, 1997) into durablemore » (Lutze, 1988) and accountable (Forsberg, 1995) waste. forms with reduced need for safeguarding (McCulhun, 1996). The composition of the Evaporator Bottoms Waste (EVB) at LANL, like that of many other I%-bearing materials, varies widely and is generally unpredictable. The goal of this study is to optimize the composition of glass for EVB waste at LANL, and present the basic techniques and tools for developing optimized glass compositions for other Pu-bearing materials in the complex. This report outlines an approach for glass formulation with fixed property restrictions, using glass property-composition databases. This approach is applicable to waste glass formulation for many variable waste streams and vitrification technologies.. Also reported are the preliminary property data for simulated evaporator bottom glasses, including glass viscosity and glass leach resistance using the Toxicity Characteristic Leaching Procedure (TCLP).« less

Radiation damage-He diffusivity models applied to deep-time thermochronology: Zircon and titanite (U-Th)/He datasets from cratonic settings

NASA Astrophysics Data System (ADS)

Guenthner, W.; DeLucia, M. S.; Marshak, S.; Reiners, P. W.; Drake, H.; Thomson, S.; Ault, A. K.; Tillberg, M.

2017-12-01

Advances in understanding the effects of radiation damage on He diffusion in uranium-bearing accessory minerals have shown the utility of damage-diffusivity models for interpreting datasets from geologic settings with long-term, low-temperature thermal histories. Craton interiors preserve a billion-year record of long-term, long-wavelength vertical motions of the lithosphere. Prior thermochronologic work in these settings has focused on radiation damage models used in conjunction with apatite (U-Th)/He dates to constrain Phanerozoic thermal histories. Owing to the more complex damage-diffusivity relationship in zircon, the zircon (U-Th)/He system yields both higher and, in some cases, lower temperature sensitivities than the apatite system, and this greater range in turn allows researchers to access deeper time (i.e., Proterozoic) segments of craton time-temperature histories. Here, we show two examples of this approach by focusing on zircon (U-Th)/He datasets from 1.8 Ga granitoids of the Fennoscandian Shield in southeastern Sweden, and 1.4 Ga granites and rhyolites of the Ozark Plateau in southeastern Missouri. In the Ozark dataset, the zircon (U-Th)/He data, combined with a damage-diffusivity model, predict negative correlations between date and effective uranium (eU) concentration (a measurement proportional to radiation damage) from thermal histories that include an episode of Proterozoic cooling (interpreted as exhumation) following reheating (interpreted as burial) to temperature of 260°C at 850-680 Ma. In the Fennoscandian Shield, a similar damage model-based approach yields time-temperature constraints with burial to 217°C between 944 Ma and 851 Ma, followed by exhumation from 850 to 500 Ma, and burial to 154°C between 366 Ma and 224 Ma. Our Fennoscandian Shield samples also include titanite (U-Th)/He dates that span a wide range (945-160 Ma) and are negatively correlated with eU concentration, analogous to our zircon He dataset. These results support the initial findings of Baughman et al. (2017, Tectonics), and suggest that further research into the radiation damage effect on He diffusion in titanite could yield a comprehensive damage-diffusivity model for the titanite (U-Th)/He thermochronometer.

Water-in-Olivine Magma Ascent Chronometry: Every Crystal is a Clock

NASA Astrophysics Data System (ADS)

Newcombe, M. E.; Asimow, P. D.; Ferriss, E.; Barth, A.; Lloyd, A. S.; Hauri, E.; Plank, T. A.

2017-12-01

The syneruptive decompression rate of basaltic magma in volcanic conduits is thought to be a critical control on eruptive vigor. Recent efforts have constrained decompression rates using models of diffusive water loss from melt embayments (Lloyd et al. 2014; Ferguson et al. 2016), olivine-hosted melt inclusions (Chen et al. 2013; Le Voyer et al. 2014), and clinopyroxene phenocrysts (Lloyd et al. 2016). However, these techniques are difficult to apply because of the rarity of melt embayments and clinopyroxene phenocrysts suitable for analysis and the complexities associated with modeling water loss from melt inclusions. We are developing a new magma ascent chronometer based on syneruptive diffusive water loss from olivine phenocrysts. We have found water zonation in every olivine phenocryst we have measured, from explosive eruptions of Pavlof, Seguam, Fuego, Cerro Negro and Kilauea volcanoes. Phenocrysts were polished to expose a central plane normal to the crystallographic `b' axis and volatile concentration profiles were measured along `a' and `c' axes by SIMS or nanoSIMS. Profiles are compared to 1D and 3D finite-element models of diffusive water loss from olivine, with or without melt inclusions, whose boundaries are in equilibrium with a melt undergoing closed-system degassing. In every case, we observe faster water diffusion along the `a' axis, consistent with the diffusion anisotropy observed by Kohlstedt and Mackwell (1998) for the so-called `proton-polaron' mechanism of H-transport. Water concentration gradients along `a' match the 1D diffusion model with a diffusivity of 10-10 m2/s (see Plank et al., this meeting), olivine-melt partition coefficient of 0.0007­-0.002 (based on melt inclusion-olivine pairs), and decompression rates equal to the best-fit values from melt embayment studies (Lloyd et al. 2014; Ferguson et al. 2016). Agreement between the melt embayment and water-in-olivine ascent chronometers at Fuego, Seguam, and Kilauea Iki demonstrates the potential of this new technique, which can be applied to any olivine-bearing mafic-intermediate eruption using common analytical tools (SIMS and FTIR). In theory, each crystal is a clock, with the potential to record variable ascent in the conduit, over the course of an eruption, and between eruptions.

Variable helium diffusion characteristics in fluorite

NASA Astrophysics Data System (ADS)

Wolff, R.; Dunkl, I.; Kempe, U.; Stockli, D.; Wiedenbeck, M.; von Eynatten, H.

2016-09-01

Precise analysis of the diffusion characteristics of helium in fluorite is crucial for establishing the new fluorite (U-Th-Sm)/He thermochronometer (FHe), which potentially provides a powerful tool for dating ore deposits unsuitable for the application of conventional geochronometers. Incremental helium outgassing experiments performed on fluorites derived from a spectrum of geological environments suggest a thermally activated volume diffusion mechanism. The diffusion behaviour is highly variable and the parameters range between log D0/a2 = 0.30 ± 0.27-7.27 ± 0.46 s-1 and Ea = 96 ± 3.5-182 ± 3.8 kJ/mol. Despite the fact that the CaF2 content of natural fluorites in most cases exceeds 99 weight percent, the closure temperature (Tc) of the fluorite (U-Th-Sm)/He thermochronometer as calculated from these diffusion parameters varies between 46 ± 14 °C and 169 ± 9 °C, considering a 125 μm fragment size. Here we establish that minor substitutions of calcium by rare earth elements and yttrium (REE + Y) and related charge compensation by sodium, fluorine, oxygen and/or vacancies in the fluorite crystal lattice have a significant impact on the diffusivity of helium in the mineral. With increasing REE + Y concentrations F vacancies are reduced and key diffusion pathways are narrowed. Consequently, a higher closure temperature is to be expected. An empirical case study confirms this variability: two fluorite samples from the same deposit (Horni Krupka, Czech Republic) with ca. 170 °C and ca. 43 °C Tc yield highly different (U-Th-Sm)/He ages of 290 ± 10 Ma and 79 ± 10 Ma, respectively. Accordingly, the fluorite sample with the high Tc could have quantitatively retained helium since the formation of the fluorite-bearing ores in the Permian, despite subsequent Mesozoic burial and associated regional hydrothermal heating. In contrast, the fluorite with the low Tc yields a Late Cretaceous age close to the apatite fission track (AFT) and apatite (U-Th)/He ages (AHe) from the same locality. Remarkably, thermal modelling of FHe yields comparable results to the well-established modelling based on AFT and AHe.

Toxic leukoencephalopathy due to yam bean seeds poisoning.

PubMed

Fu, Pin-Kuei; Wang, Pao-Yu

2012-07-01

Toxic leukoencephalopathy is attributed to exposure to a wide variety of agents, including systemic chemotherapy, cranial irradiation, illicit drug abuse, and toxins from the environment. Diagnosis of this disease requires documented exposure to a toxin, neurobehavioral deficits, and typical neuroimaging abnormalities. Intoxication by compounds extracted from yam bean seeds may mimic cyanide poisoning but fail to respond to antidotal therapy. We report a 54-year-old Chinese woman who developed disturbed consciousness after eating 40 pieces of yam bean seeds. Head computed tomography obtained 24 hours after the episode was normal. However, magnetic resonance imaging obtained 20 days after the episode revealed symmetrical faint high signal over the bilateral periventricular white matter on T1-weighted image, which turned into diffuse and symmetrical bright high signal on FLAIR. The diagnosis of this patient was toxic leukoencephalopathy by yam bean seeds intoxication. The changes in brain images after yam bean seeds intoxication have not ever been reported. Physicians in Asia and the Pacific islands should have a high index of suspicion when they care for patients with acute confusion and a high anion gap metabolic acidosis but normal serum cyanide level.

Default mode network as a potential biomarker of chemotherapy-related brain injury

PubMed Central

Kesler, Shelli R.

2014-01-01

Chronic medical conditions and/or their treatments may interact with aging to alter or even accelerate brain senescence. Adult onset cancer, for example, is a disease associated with advanced aging and emerging evidence suggests a profile of subtle but diffuse brain injury following cancer chemotherapy. Breast cancer is currently the primary model for studying these “chemobrain” effects. Given the widespread changes to brain structure and function as well as the common impairment of integrated cognitive skills observed following breast cancer chemotherapy, it is likely that large-scale brain networks are involved. Default mode network (DMN) is a strong candidate considering its preferential vulnerability to aging and sensitivity to toxicity and disease states. Additionally, chemotherapy is associated with several physiologic effects including increased inflammation and oxidative stress that are believed to elevate toxicity in the DMN. Biomarkers of DMN connectivity could aid in the development of treatments for chemotherapy-related cognitive decline. For example, certain nutritional interventions could potentially reduce the metabolic changes (e.g. amyloid beta toxicity) associated with DMN disruption. PMID:24913897

[Rarer causes of thyrotoxicosis].

PubMed

Krysiak, Robert; Kowalcze, Karolina; Okopień, Bogusław

2016-01-01

Thyrotoxicosis is a pathological syndrome in which tissue is exposed to excessive amounts of circulating thyroid hormones. Including its subclinical form, it is considered as one of the most frequent endocrine disorders in the general population. If not detected in a timely fashion, thyrotoxicosis can have serious health consequences. The most common forms of thyrotoxicosis include diffuse toxic goiter (Graves' disease), toxic multinodular goiter (Plummer's disease), and toxic adenoma (Goetsch's disease). The significant progress in the fields of hormonal assessment, imaging procedures and molecular biology made in recent years has brought about great improvement in the identification, differentiation and treatment of many other disorders associated with thyrotoxicosis. Therefore, this paper discusses the etiopathogenesis, clinical manifestation, biochemical abnormalities and management of thyrotropinoma, resistance to thyroid hormone, de Quervain's, silent, acute, posttraumatic and radiation-induced thyroiditis, Riedel's goiter, differentiated thyroid cancer, struma ovarii, thyrotoxicosis factitia, other forms of iatrogenic thyrotoxicosis, gestational trophoblastic disease, neonatal Graves's disease, familial nonautoimmune hyperthyroidism and McCune-Albright syndrome. On the basis of available studies, some of whom were carried out in the recent years, we provide practical guidelines for clinical endocrinologists dealing with the diagnosis and treatment of thyrotoxicosis.

Mutant LRRK2 Toxicity in Neurons Depends on LRRK2 Levels and Synuclein But Not Kinase Activity or Inclusion Bodies

PubMed Central

Skibinski, Gaia; Nakamura, Ken; Cookson, Mark R.

2014-01-01

By combining experimental neuron models and mathematical tools, we developed a “systems” approach to deconvolve cellular mechanisms of neurodegeneration underlying the most common known cause of Parkinson's disease (PD), mutations in leucine-rich repeat kinase 2 (LRRK2). Neurons ectopically expressing mutant LRRK2 formed inclusion bodies (IBs), retracted neurites, accumulated synuclein, and died prematurely, recapitulating key features of PD. Degeneration was predicted from the levels of diffuse mutant LRRK2 that each neuron contained, but IB formation was neither necessary nor sufficient for death. Genetic or pharmacological blockade of its kinase activity destabilized LRRK2 and lowered its levels enough to account for the moderate reduction in LRRK2 toxicity that ensued. By contrast, targeting synuclein, including neurons made from PD patient-derived induced pluripotent cells, dramatically reduced LRRK2-dependent neurodegeneration and LRRK2 levels. These findings suggest that LRRK2 levels are more important than kinase activity per se in predicting toxicity and implicate synuclein as a major mediator of LRRK2-induced neurodegeneration. PMID:24403142

Interfacing nanostructures to biological cells

DOEpatents

Chen, Xing; Bertozzi, Carolyn R.; Zettl, Alexander K.

2012-09-04

Disclosed herein are methods and materials by which nanostructures such as carbon nanotubes, nanorods, etc. are bound to lectins and/or polysaccharides and prepared for administration to cells. Also disclosed are complexes comprising glycosylated nanostructures, which bind selectively to cells expressing glycosylated surface molecules recognized by the lectin. Exemplified is a complex comprising a carbon nanotube functionalized with a lipid-like alkane, linked to a polymer bearing repeated .alpha.-N-acetylgalactosamine sugar groups. This complex is shown to selectively adhere to the surface of living cells, without toxicity. In the exemplified embodiment, adherence is mediated by a multivalent lectin, which binds both to the cells and the .alpha.-N-acetylgalactosamine groups on the nanostructure.

Acute Dermal Toxicity of Diethyleneglycol Dinitrate (TEGDN) in Rabbits

DTIC Science & Technology

1989-01-01

hydrometra, left uterine horn. 36483 - 84F690 Female - No lesions. 36484 - 84F691 Female - Ears - otitis media , purulent, bilateral. 36485- 84F692...Female - Liver - four white foci, 2-4mm in diameter Ears - otitis media , purulent, bilateral 36486 - 84F693 Female - Skin - diffuse red mottling over...spine; Ears - otitis media , purulent, bilateral. 3b487 - 84F704 Male - No lesions. 36488 - 84F705 Male - No lesions. 36489 - 84F706 Half Cecum

A diffusion climatology for Cape Canaveral, Florida

NASA Technical Reports Server (NTRS)

Siler, R. K.

1980-01-01

The problem of toxic effluent released by a space shuttle launch on local plant and animal life is discussed. Based on several successive years of data, nine basic weather patterns were identified, and the probabilities of pattern occurrence, of onshore/alongshore cloud transport, of precipitation accompanying the latter, and of ground-level concentrations of hydrogen chloride were determined. Diurnal variations for the patterns were also investigated. Sketches showing probable movement of launch cloud exhaust and isobaric maps are presented.

Antimicrobial activity of plant extracts against the honeybee pathogens, Paenibacillus larvae and Ascosphaera apis and their topical toxicity to Apis mellifera adults.

PubMed

Chaimanee, V; Thongtue, U; Sornmai, N; Songsri, S; Pettis, J S

2017-11-01

To explore alternative nonchemical control measures against two honeybee pathogens, Paenibacillus larvae and Ascosphaera apis, 37 plant species were screened for antimicrobial activity. The activity of selected plant extracts was screened using an in vitro disc diffusion assay and the minimal inhibitory concentration (MIC) was determined by the broth microdilution method. The results showed that 36 plant extracts had some antibacterial activity on P. larvae by disc diffusion assay. Chromolaena odorata showed the greatest antibacterial activity against P. larvae (MIC 16-64 μg ml -1 ). Of the 37 tested plants, only seven species, Amomum krervanh, Allium sativum, Cinnamomum sp., Piper betle, Piper ribesioides, Piper sarmentosum and Syzygium aromaticum had inhibitory effects on A. apis (MICs of 32-64 μg ml -1 ). The results demonstrated that promising plant extracts were not toxic to adult bees at the concentrations used in this study. The results demonstrate the potential antimicrobial activity of natural products against honeybee diseases caused by P. larvae and A. apis. Chromolaena odorata in particular showed high bioactivity against P. larvae. Further study is recommended to develop these nonchemical treatments against American foulbrood and chalkbrood in honeybees. This work proposes new natural products for the control of American foulbrood and chalkbrood in honeybees. © 2017 The Society for Applied Microbiology.

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

Lv, Chao; Aitchison, Erick W.; Wu, Dongsheng

Hydrogen sulfide (H 2S), a commonly known toxic gas compound, possesses unique chemical features that allow this small solute molecule to quickly diffuse through cell membranes. Taking advantage of the recent orthogonal space tempering (OST) method, we comparatively mapped the transmembrane free energy landscapes of H 2S and its structural analogue, water (H 2O), seeking to decipher the molecular determinants that govern their drastically different permeabilities. Here, as revealed by our OST sampling results, in contrast to the highly polar water solute, hydrogen sulfide is evidently amphipathic, and thus inside membrane is favorably localized at the interfacial region, that is,more » the interface between the polar head-group and nonpolar acyl chain regions. Because the membrane binding affinity of H 2S is mainly governed by its small hydrophobic moiety and the barrier height inbetween the interfacial region and the membrane center is largely determined by its moderate polarity, the transmembrane free energy barriers to encounter by this toxic molecule are very small. Moreover when H2S diffuses from the bulk solution to the membrane center, the above two effects nearly cancel each other, so as to lead to a negligible free energy difference. Lastly, this study not only explains why H 2S can quickly pass through cell membranes but also provides a practical illustration on how to use the OST free energy sampling method to conveniently analyze complex molecular processes.« less

Mini-DIAL system measurements coupled with multivariate data analysis to identify TIC and TIM simulants: preliminary absorption database analysis.

NASA Astrophysics Data System (ADS)

Gaudio, P.; Malizia, A.; Gelfusa, M.; Martinelli, E.; Di Natale, C.; Poggi, L. A.; Bellecci, C.

2017-01-01

Nowadays Toxic Industrial Components (TICs) and Toxic Industrial Materials (TIMs) are one of the most dangerous and diffuse vehicle of contamination in urban and industrial areas. The academic world together with the industrial and military one are working on innovative solutions to monitor the diffusion in atmosphere of such pollutants. In this phase the most common commercial sensors are based on “point detection” technology but it is clear that such instruments cannot satisfy the needs of the smart cities. The new challenge is developing stand-off systems to continuously monitor the atmosphere. Quantum Electronics and Plasma Physics (QEP) research group has a long experience in laser system development and has built two demonstrators based on DIAL (Differential Absorption of Light) technology could be able to identify chemical agents in atmosphere. In this work the authors will present one of those DIAL system, the miniaturized one, together with the preliminary results of an experimental campaign conducted on TICs and TIMs simulants in cell with aim of use the absorption database for the further atmospheric an analysis using the same DIAL system. The experimental results are analysed with standard multivariate data analysis technique as Principal Component Analysis (PCA) to develop a classification model aimed at identifying organic chemical compound in atmosphere. The preliminary results of absorption coefficients of some chemical compound are shown together pre PCA analysis.

Comparison of soil solution speciation and diffusive gradients in thin-films measurement as an indicator of copper bioavailability to plants.

PubMed

Zhao, Fang-Jie; Rooney, Corinne P; Zhang, Hao; McGrath, Steve P

2006-03-01

The toxicity effect concentrations (10% effective concentration [EC10] and 50% effective concentration [EC50]) of total added Cu derived from barley root elongation and tomato growth assays varied widely among 18 European soils. We investigated whether this variation could be explained by the solubility or speciation of Cu in soil solutions or the diffusive gradients in thin-films (DGT) measurement. Solubility and Cu speciation varied greatly among the soils tested. However, the EC10 and EC50 of soil solution Cu or free Cu2+ activity varied even more widely than those based on the total added Cu, indicating that solubility or soil solution speciation alone could not explain intersoil variation in Cu toxicity. Estimated EC10 and EC50 of free Cu2+ activity correlated closely and negatively with soil pH, indicating a protective effect of H+, which is consistent with the biotic ligand model concept. The DGT measurement was found to narrow the intersoil variation in EC50 considerably and to be a better predictor of plant Cu concentrations than either soil solution Cu or free Cu2+ activity. We conclude that plant bioavailability of Cu in soil depends on Cu speciation, interactions with protective ions (particularly H+), and the resupply from the solid phase, and we conclude that the DGT measurement provides a useful indicator of Cu bioavailability in soil.

Therapeutic Efficacy of a {sup 188}Re-Labeled {alpha}-Melanocyte-Stimulating Hormone Peptide Analog in Murine and Human Melanoma-Bearing Mouse Models

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

Miao, Yubin; Owen, Nellie K.; Fisher, Darrell R.

2005-01-01

The purpose of this study was to examine the therapeutic efficacy of {sup 188}Re-(Arg{sup 11})CCMSH in the B16/F1 murine melanoma and TXM13 human melanoma bearing mouse models. Method: (Arg11)CCMSH was synthesized and labeled with {sup 188}Re to form {sup 188}Re-(Agr{sup 11})CCMSH. B16/F1 melanoma tumor bearing mice were administrated with 200 Ci, 600 Ci and 2x400 Ci of {sup 188}Re-(Arg{sup 11})CCMSH via the tail vein, respectively. TXM13 melanoma tumor hearing mice were separately injected with 600 Ci, 2x400 Ci and 1000 Ci of 100Re-(Arg{sup 11})CCMSH through the tail vein. Two groups of 10 mice bearing either B16/F1 or TXM13 tumors weremore » injected with saline as untreated controls. Results: In contrast to the untreated control group, {sup 188}Re(Arg11)CCMSH yielded rapid and lasting therapeutic effects in the treatment groups with either B16/F1 or TXM13 tumors. The tumor growth rate was reduced and the survival rate was prolonged in the treatment groups. Treatment with 2x400 Ci of {sup 188}Re-Arg{sup 11}CCMSH significantly extended the mean life of B16/F1 tumor mice (p<0.05), while the mean life of TXm13 tumor mice was significantly prolonged after treatment with 600 Ci and 1000 Ci doses of {sup 188}Re-(Arg{sup 11})CCMSH (p<0.05 High-dose {sup 188}Re-(Arg{sup 11}))CCMSH produced no observed normal-tissue toxicity. Conclusions: The therapy study results revealed that {sup 188}Re-Arg11 CCMSH yielded significant therapeutic effects in both B16/F1 murine melanoma and TXM13 human melanoma bearing mouse models. {sup 188}Re-(Arg{sup 11})CCMSH appears to be a promising radiolabeled peptide for targeted radionuclide therapy of melanoma.« less

Preparation and characterization of nickel-spiked freshwater sediments for toxicity tests: toward more environmentally realistic nickel partitioning

USGS Publications Warehouse

Brumbaugh, William G.; Besser, John M.; Ingersoll, Christopher G.; May, Thomas W.; Ivey, Chris D.; Schlekat, Christian E.; Garman, Emily R.

2013-01-01

Two spiking methods were compared and nickel (Ni) partitioning was evaluated during a series of toxicity tests with 8 different freshwater sediments having a range of physicochemical characteristics. A 2-step spiking approach with immediate pH adjustment by addition of NaOH at a 2:1 molar ratio to the spiked Ni was effective in producing consistent pH and other chemical characteristics across a range of Ni spiking levels. When Ni was spiked into sediment having a high acid-volatile sulfide and organic matter content, a total equilibration period of at least 10 wk was needed to stabilize Ni partitioning. However, highest spiking levels evidently exceeded sediment binding capacities; therefore, a 7-d equilibration in toxicity test chambers and 8 volume-additions/d of aerobic overlying water were used to avoid unrealistic Ni partitioning during toxicity testing. The 7-d pretest equilibration allowed excess spiked Ni and other ions from pH adjustment to diffuse from sediment porewater and promoted development of an environmentally relevant, 0.5- to 1-cm oxic/suboxic sediment layer in the test chambers. Among the 8 different spiked sediments, the logarithm of sediment/porewater distribution coefficient values (log Kd) for Ni during the toxicity tests ranged from 3.5 to 4.5. These Kd values closely match the range of values reported for various field Ni-contaminated sediments, indicating that testing conditions with our spiked sediments were environmentally realistic.

Site-specific hydration and dehydration of San Carlos olivine

NASA Astrophysics Data System (ADS)

Ferriss, E.; Plank, T. A.; Walker, D.

2016-12-01

Hydrogen incorporation and diffusion in olivine is critical to understanding fundamental Earth processes such as mantle rheology, plate tectonics, melt generation and magma ascent. Interpreting measured H profiles in olivine requires a more comprehensive understanding of H point defect reactions than currently exists because H diffusivity (D) ranges over 6 orders of magnitude, from slow diffusing H incorporated as (4H+)Si­ [1] to rapid `proton-polaron' bulk H diffusion [2]. Here we present the first experiments on H diffusing into and then out of Fe-bearing olivine using the whole-block method [3], which allows a finely-resolved time series of H profiles in 3 crystallographic directions using the same sample for all dehydration steps. A piece of nearly-dry, oriented San Carlos olivine was hydrated in a piston cylinder apparatus using H2O and solid buffers of Ni/NiO and San Carlos olivine and enstatite at 800 °C and 10 kbar for 17.5 hours, just long enough to saturate the `proton-polaron' mechanism. The sample was then dehydrated in a CO/CO2 gas-mixing furnace at 800°C and 10-14 bar fO2 for total heating times of 1, 3, 7, 13, 19, 43, and 68 hrs, at which point most, but not all, of the H had left the crystal. FTIR profiles at 1, 3, and 7 hours show bulk H profiles consistent with `proton-polaron' diffusion. Later the pace of dehydration slowed, and in several cases the bulk H profile shape differed from what would be expected during simple diffusive loss. The small peak at 3600 cm-1, (4H+)Si, remained essentially unchanged throughout all experiments. The peak at 3573 cm-1, (Ti4+)Mg(2H+)Mg, was initially present but tiny, grew to become the largest peak after hydration, and then during dehydration returned to its initial height. The apparent diffusivity of this peak during hydration and the initial stages of dehydration is 4 orders of magnitude faster than the same peak in synthetic forsterite [2]. Peaks at 3542, 3525, 3489, and 3480 cm-1 were not present initially, grew during hydration, and were removed completely during dehydration. No lower-wavenumber H peaks were observed. These results represent a major step toward reconciling the peak-specific understanding of H diffusion [1] with the 2-mechanism H bulk diffusion model [2]. [1] Padrón-Navarta et al. 2014 [2] Kohlstedt & Mackwell 1998 [3] Ferriss et al. 2015

Plasmonic Nanobubbles Rapidly Detect and Destroy Drug-Resistant Tumors

PubMed Central

Lukianova-Hleb, Ekaterina Y.; Ren, Xiaoyang; Townley, Debra; Wu, Xiangwei; Kupferman, Michael E.; Lapotko, Dmitri O.

2012-01-01

The resistance of residual cancer cells after oncological resection to adjuvant chemoradiotherapies results in both high recurrence rates and high non-specific tissue toxicity, thus preventing the successful treatment of such cancers as head and neck squamous cell carcinoma (HNSCC). The patients' survival rate and quality of life therefore depend upon the efficacy, selectivity and low non-specific toxicity of the adjuvant treatment. We report a novel, theranostic in vivo technology that unites both the acoustic diagnostics and guided intracellular delivery of anti-tumor drug (liposome-encapsulated doxorubicin, Doxil) in one rapid process, namely a pulsed laser-activated plasmonic nanobubble (PNB). HNSCC-bearing mice were treated with gold nanoparticle conjugates, Doxil, and single near-infrared laser pulses of low energy. Tumor-specific clusters of gold nanoparticles (solid gold spheres) converted the optical pulses into localized PNBs. The acoustic signals of the PNB detected the tumor with high specificity and sensitivity. The mechanical impact of the PNB, co-localized with Doxil liposomes, selectively ejected the drug into the cytoplasm of cancer cells. Cancer cell-specific generation of PNBs and their intracellular co-localization with Doxil improved the in vivo therapeutic efficacy from 5-7% for administration of only Doxil or PNBs alone to 90% thus demonstrating the synergistic therapeutic effect of the PNB-based intracellular drug release. This mechanism also reduced the non-specific toxicity of Doxil below a detectable level and the treatment time to less than one minute. Thus PNBs combine highly sensitive diagnosis, overcome drug resistance and minimize non-specific toxicity in a single rapid theranostic procedure for intra-operative treatment. PMID:23139725

Comparison of Efficacy and Toxicity of Traditional Chinese Medicine (TCM) Herbal Mixture LQ and Conventional Chemotherapy on Lung Cancer Metastasis and Survival in Mouse Models

PubMed Central

Zhang, Lei; Wu, Chengyu; Zhang, Yong; Liu, Fang; Wang, Xiaoen; Zhao, Ming; Hoffman, Robert M.

2014-01-01

Unlike Western medicine that generally uses purified compounds and aims to target a single molecule or pathway, traditional Chinese medicine (TCM) compositions usually comprise multiple herbs and components that are necessary for efficacy. Despite the very long-time and wide-spread use of TCM, there are very few direct comparisons of TCM and standard cytotoxic chemotherapy. In the present report, we compared the efficacy of the TCM herbal mixture LQ against lung cancer in mouse models with doxorubicin (DOX) and cyclophosphamide (CTX). LQ inhibited tumor size and weight measured directly as well as by fluorescent-protein imaging in subcutaneous, orthotopic, spontaneous experimental metastasis and angiogenesis mouse models of lung cancer. LQ was efficacious against primary and metastatic lung cancer without weight loss and organ toxicity. In contrast, CTX and DOX, although efficacious in the lung cancer models caused significant weight loss, and organ toxicity. LQ also had anti-angiogenic activity as observed in lung tumors growing in nestin-driven green fluorescent protein (ND-GFP) transgenic nude mice, which selectively express GFP in nascent blood vessels. Survival of tumor-bearing mice was also prolonged by LQ, comparable to DOX. In vitro, lung cancer cells were killed by LQ as observed by time-lapse imaging, comparable to cisplatinum. LQ was more potent to induce cell death on cancer cell lines than normal cell lines unlike cytotoxic chemotherapy. The results indicate that LQ has non-toxic efficacy against metastatic lung cancer. PMID:25286158

Selective cytoprotective effect of histamine on doxorubicin-induced hepatic and cardiac toxicity in animal models

PubMed Central

Lamas, DJMartinel; Nicoud, MB; Sterle, HA; Carabajal, E; Tesan, F; Perazzo, JC; Cremaschi, GA; Rivera, ES; Medina, VA

2015-01-01

The aim of the present work was to evaluate the potential protective effect of histamine on Doxorubicin (Dox)-induced hepatic and cardiac toxicity in different rodent species and in a triple-negative breast tumor-bearing mice model. Male Sprague Dawley rats and Balb/c mice were divided into four groups: control (received saline), histamine (5 mg/kg for rats and 1 mg/kg for mice, daily subcutaneous injection starting 24 h before treatment with Dox), Dox (2 mg/kg, intraperitoneally injected three times a week for 2 weeks) and Dox+histamine (received both treatments). Tissue toxicity was evaluated by histopathological studies and oxidative stress and biochemical parameters. The combined effect of histamine and Dox was also investigated in vitro and in vivo in human MDA-MB-231 triple-negative breast cancer model. Heart and liver of Dox-treated animals displayed severe histological damage, loss of tissue weight, increased TBARS levels and DNA damage along with an augment in serum creatine kinase-myocardial band. Pretreatment with histamine prevented Dox-induced tissue events producing a significant preservation of the integrity of both rat and mouse myocardium and liver, through the reduction of Dox-induced oxidative stress and apoptosis. Histamine treatment preserved anti-tumor activity of Dox, exhibiting differential cytotoxicity and increasing the Dox-induced inhibition of breast tumor growth. Findings provide preclinical evidence indicating that histamine could be a promising candidate as a selective cytoprotective agent for the treatment of Dox-induced cardiac and hepatic toxicity, and encourage the translation to clinical practice. PMID:27551485

The antitumoral effect of the American mistletoe Phoradendron serotinum (Raf.) M.C. Johnst. (Viscaceae) is associated with the release of immunity-related cytokines.

PubMed

Alonso-Castro, Angel Josabad; Juárez-Vázquez, Maria Del Carmen; Domínguez, Fabiola; González-Sánchez, Ignacio; Estrada-Castillón, Eduardo; López-Toledo, Gabriela; Chávez, Marco; Cerbón, Marco A; García-Carranca, Alejandro

2012-08-01

Phoradendron serotinum is commonly used in Mexican traditional medicine for the empirical treatment of cancer. However, there are no studies regarding the antitumoral or immunomodulatory activities of Phoradendron serotinum. The in vivo toxicity of ethanolic extracts of Phoradendron serotinum (PSE) was evaluated in mice according to the Lorke procedure. The in vitro immunomodulatory effects of PSE were evaluated estimating the effects of PSE on the pinocytosis, NO production and lysosomal enzyme activity in murine macrophages RAW 264.7. The effects of PSE on the proliferation of murine splenocytes and NK cell activity were also assayed. The cytotoxic effects on TC-1 (lung murine cancer cells) were evaluated using the MTT assay, whereas the apoptotic effect of PSE on TC-1 cells was evaluated using TUNEL assay. Also, different doses of PSE were injected intraperitoneally daily into C57BL/6 mice bearing tumors of TC-1 cells during 25 days. The growth and weight of tumors was measured. In addition, the levels of IL-2, IL-6, IL-12, IL-23 and IFN-γ in murine serum and supernatants of K562 cell-murine splenocyte cocultures were measured. PSE stimulated the proliferation, pinocytosis and lysosomal enzyme activity in murine macrophages with a similar potency than lypopolisaccharides 1 μg/ml. In addition, PSE stimulated the proliferation of murine splenocytes and induced the NK cell activity. PSE showed cytotoxic (IC(50)=1.9 μg/ml) and apoptotic effects against TC-1 cells. The LD(50) was 125 mg/kg by intraperitoneal route (i.p.) and 375 mg/kg by oral route. PSE administrated at 1, 5 and 10 mg/kg i.p. inhibited the tumor growth by 18%, 40% and 69%, respectively, in mice bearing TC-1 tumor. PSE increased the in vitro and in vivo release of IL-2, IL-6 and IFN-γ but lacked effect on IL-12 and IL-23 release. Phoradendron serotinum shows moderate toxic effects in vivo, exerts cytotoxic and apoptotic effects on TC-1 cells. Phoradendron serotinum also has antitumor effects in mice bearing TC-1 tumor and induces immunomodulatory activities in vivo. The results suggest that antitumoral effects of PSE are related with the production of immunity-related cytokines. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Linking pore-scale and basin-scale effects on diffusive methane transport in hydrate bearing environments through multi-scale reservoir simulations

NASA Astrophysics Data System (ADS)

Nole, M.; Daigle, H.; Cook, A.; Malinverno, A.; Hillman, J. I. T.

2016-12-01

We explore the gas hydrate-generating capacity of diffusive methane transport induced by solubility gradients due to pore size contrasts in lithologically heterogeneous marine sediments. Through the use of 1D, 2D, and 3D reactive transport simulations, we investigate scale-dependent processes in diffusion-dominated gas hydrate systems. These simulations all track a sand body, or series of sands, surrounded by clays as they are buried through the gas hydrate stability zone. Methane is sourced by microbial methanogenesis in the clays surrounding the sand layers. In 1D, simulations performed in a Lagrangian reference frame demonstrate that gas hydrate in thin sands (3.6 m thick) can occur in high saturations (upward of 70%) at the edges of sand bodies within the upper 400 meters below the seafloor. Diffusion of methane toward the center of the sand layer depends on the concentration gradient within the sand: broader sand pore size distributions with smaller median pore sizes enhance diffusive action toward the sand's center. Incorporating downhole log- and laboratory-derived sand pore size distributions, gas hydrate saturations in the center of the sand can reach 20% of the hydrate saturations at the sand's edges. Furthermore, we show that hydrate-free zones exist immediately above and below the sand and are approximately 5 m thick, depending on the sand-clay solubility contrast. A moving reference frame is also adopted in 2D, and the angle of gravity is rotated relative to the grid system to simulate a dipping sand layer. This is important to minimize diffusive edge effects or numerical diffusion that might be associated with a dipping sand in an Eulerian grid system oriented orthogonal to gravity. Two-dimensional simulations demonstrate the tendency for gas hydrate to accumulate downdip in a sand body because of greater methane transport at depth due to larger sand-clay solubility contrasts. In 3D, basin-scale simulations illuminate how convergent sand layers in a multilayered system can compete for diffusion from clays between them, resulting in relatively low hydrate saturations. All simulations suggest that when hydrate present in clays dissociates with burial, the additional dissolved methane is soaked up by nearby sands preserving high hydrate saturations.

Diffusive exchange of trace elements between basaltic-andesite and dacitic melt: Insights into potential metal fractionation during magma mixing

NASA Astrophysics Data System (ADS)

Fiege, A.; Ruprecht, P.; Simon, A. C.; Holtz, F.

2017-12-01

Mafic magma recharge is a common process that triggers physical and chemical mixing in magmatic systems and drives their evolution, resulting in, e.g., hybridization and volcanic eruptions. Once magma-magma contact is initiated, rapid heat-flux commonly leads to the formation of a cooling-induced crystal mush on the mafic side of the interface. Here, on a local scale (µm to cm), at the magma-magma interface, melt-melt diffusive exchange is required to approach equilibrium. Significant chemical potential gradients drive a complex, multi-element mass flux between the two systems (Liang, 2010). This diffusive-equilibration often controls crystal dissolution rates within the boundary layers and, thus, the formation of interconnected melt or fluid networks. Such networks provide important pathways for the transport of volatiles and trace metals from the mafic recharge magma to the felsic host magma, where the latter may feed volcanic activities and ore deposits. While major element diffusion in silicate melts is mostly well understood, even in complex systems, the available data for many trace element metals are limited (Liang, 2010; Zhang et al., 2010). Differences in diffusivity in a dynamic, mixing environment can cause trace element fractionation, in particular during crystallization and volatile exsolution and separation. This may affect trace element signatures in phenocrysts and magmatic volatile phases that can form near a magma-magma boundary. As a result, the chemistry of volcanic gases and magmatic-hydrothermal ore deposits may be partially controlled by such mixing phenomena. We performed melt-melt diffusion-couple experiments at 150 MPa, 1100°C, FMQ, FMQ+1 and FMQ+3 (FMQ: fayalite-magnetite-quartz oxygen fugacity buffer). Hydrated, sulfur-bearing cylinders of dacite and basaltic andesite were equilibrated for up to 20 h. Major and trace element gradients were measured by using laser-ablation ICP-MS and electron microprobe analyses. The results we will present will help to fill data gaps for the diffusivity of certain metals in silicate melts (e.g., V, Mo, W). First data analyses indicate a higher diffusivity of V when compared to W . Liang (2010) Rev Mineral Geochem 72, 409-446; Zhang et al. (2010) Rev Mineral Geochem 72, 311-408.

Linking pore-scale and basin-scale effects on diffusive methane transport in hydrate bearing environments through multi-scale reservoir simulations

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

Nole, Michael; Daigle, Hugh; Cook, Ann

We explore the gas hydrate-generating capacity of diffusive methane transport induced by solubility gradients due to pore size contrasts in lithologically heterogeneous marine sediments. Through the use of 1D, 2D, and 3D reactive transport simulations, we investigate scale-dependent processes in diffusion-dominated gas hydrate systems. These simulations all track a sand body, or series of sands, surrounded by clays as they are buried through the gas hydrate stability zone. Methane is sourced by microbial methanogenesis in the clays surrounding the sand layers. In 1D, simulations performed in a Lagrangian reference frame demonstrate that gas hydrate in thin sands (3.6 m thick)more » can occur in high saturations (upward of 70%) at the edges of sand bodies within the upper 400 meters below the seafloor. Diffusion of methane toward the center of the sand layer depends on the concentration gradient within the sand: broader sand pore size distributions with smaller median pore sizes enhance diffusive action toward the sand’s center. Incorporating downhole log- and laboratory-derived sand pore size distributions, gas hydrate saturations in the center of the sand can reach 20% of the hydrate saturations at the sand’s edges. Furthermore, we show that hydrate-free zones exist immediately above and below the sand and are approximately 5 m thick, depending on the sand-clay solubility contrast. A moving reference frame is also adopted in 2D, and the angle of gravity is rotated relative to the grid system to simulate a dipping sand layer. This is important to minimize diffusive edge effects or numerical diffusion that might be associated with a dipping sand in an Eulerian grid system oriented orthogonal to gravity. Two-dimensional simulations demonstrate the tendency for gas hydrate to accumulate downdip in a sand body because of greater methane transport at depth due to larger sand-clay solubility contrasts. In 3D, basin-scale simulations illuminate how convergent sand layers in a multilayered system can compete for diffusion from clays between them, resulting in relatively low hydrate saturations. All simulations suggest that when hydrate present in clays dissociates with burial, the additional dissolved methane is soaked up by nearby sands preserving high hydrate saturations.« less

Environmental labeling of car tires--toxicity to Daphnia magna can be used as a screening method.

PubMed

Wik, Anna; Dave, Göran

2005-02-01

Car tires contain several water-soluble compounds that can leach into water and have toxic effects on aquatic organisms. Due to tire wear, 10,000 tonnes of rubber particles end up along the Swedish roads every year. This leads to a diffuse input of emissions of several compounds. Emissions of polyaromatic hydrocarbons (PAHs) are of particular concern. PAHs are ingredients of the high aromatic oil (HA oil) that is used in the rubber as a softener and as a filler. The exclusion of HA oils from car tires has started, and an environmental labeling of tires could make HA oils obsolete. The toxicity to Daphnia magna from 12 randomly selected car tires was tested in this study. Rubber from the tread of the tires was grated into small pieces, to simulate material from tire wear, and the rubber was equilibrated with dilution water for 72 h before addition of test organisms. The 24-h EC50s of the rubber pieces ranged from 0.29 to 32 gl-1, and the 48-h EC50s ranged from 0.0625 to 2.41 gl-1. Summer tires were more toxic than winter tires. After the 48-h exposure, the daphnids were exposed to UV-light for 2 h, to determine if the tires contained compounds that were phototoxic. After UV-activation the EC50s ranged from 0.0625 to 0.38 gl-1. Four of the 12 tires had a very distinct photoactivation, with a toxicity increase of >10 times. This study has shown that the used method for toxicity testing with Daphnia magna according to ISO 6341 could be used as a basis for environmental labeling of car tires.

Assessment of the In Vivo Toxicity of Gold Nanoparticles

NASA Astrophysics Data System (ADS)

Chen, Yu-Shiun; Hung, Yao-Ching; Liau, Ian; Huang, G. Steve

2009-08-01

The environmental impact of nanoparticles is evident; however, their toxicity due to their nanosize is rarely discussed. Gold nanoparticles (GNPs) may serve as a promising model to address the size-dependent biological response to nanoparticles because they show good biocompatibility and their size can be controlled with great precision during their chemical synthesis. Naked GNPs ranging from 3 to 100 nm were injected intraperitoneally into BALB/C mice at a dose of 8 mg/kg/week. GNPs of 3, 5, 50, and 100 nm did not show harmful effects; however, GNPs ranging from 8 to 37 nm induced severe sickness in mice. Mice injected with GNPs in this range showed fatigue, loss of appetite, change of fur color, and weight loss. Starting from day 14, mice in this group exhibited a camel-like back and crooked spine. The majority of mice in these groups died within 21 days. Injection of 5 and 3 nm GNPs, however, did not induce sickness or lethality in mice. Pathological examination of the major organs of the mice in the diseased groups indicated an increase of Kupffer cells in the liver, loss of structural integrity in the lungs, and diffusion of white pulp in the spleen. The pathological abnormality was associated with the presence of gold particles at the diseased sites, which were verified by ex vivo Coherent anti-Stoke Raman scattering microscopy. Modifying the surface of the GNPs by incorporating immunogenic peptides ameliorated their toxicity. This reduction in the toxicity is associated with an increase in the ability to induce antibody response. The toxicity of GNPs may be a fundamental determinant of the environmental toxicity of nanoparticles.

In vitro antibacterial activity and acute toxicity studies of aqueous-methanol extract of Sida rhombifolia Linn. (Malvaceae)

PubMed Central

2010-01-01

Background Many bacteria among the Enterobacteria family are involved in infectious diseases and diarrhoea. Most of these bacteria become resistant to the most commonly used synthetic drugs in Cameroon. Natural substances seem to be an alternative to this problem. Thus the aim of this research was to investigate the in vitro antibacterial activity of the methanol and aqueous-methanol extracts of Sida rhombifolia Linn (Malvaceae) against seven pathogenic bacteria involved in diarrhoea. Acute toxicity of the most active extract was determined and major bioactive components were screened. Methods The agar disc diffusion and the agar dilution method were used for the determination of inhibition diameters and the Minimum Inhibitory Concentration (MICs) respectively. The acute toxicity study was performed according WHO protocol. Results The aqueous-methanol extract (1v:4v) was the most active with diameters of inhibition zones ranging from 8.7 - 23.6 mm, however at 200 μg/dic this activity was relatively weak compared to gentamycin. The MICs of the aqueous-methanol extract (1v:4v) varied from 49.40 to 78.30 μg/ml. Salmonella dysenteriae was the most sensitive (49.40 μg/ml). For the acute toxicity study, no deaths of rats were recorded. However, significant increase of some biochemical parameters such as aspartate amino-transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and creatinine (CRT) were found. The phytochemical analysis of the aqueous methanol extract indicated the presence of tannins, polyphenols, alkaloids, glycosides, flavonoids and saponins Conclusion The results showed that the aqueous-methanol extract of S. rhombifolia exhibited moderate antibacterial activity. Some toxic effects were found when rats received more than 8 g/kg bw of extract. Antibacterial; Enterobacteria; Acute toxicity; Phytochemical analysis PMID:20663208

Inhibition of toxic actions of phospholipase A2 isolated & characterized from the Indian Banded Krait (Bungarus fasciatus) venom by synthetic herbal compounds

PubMed Central

Gomes, Antony; Bhattacharya, Shamik; Mukherjee, Sanghamitra; Inn-ho-Tsai; Gomes, Aparna

2012-01-01

Background & objectives: Phospholipase A2 (PLA2) is one of the major constituents of krait venom associated with several pathophysiological actions like myotoxicity, cardiotoxicity, neurotoxicity, etc. As there was no specific antiserum available against Bungarus fasciatus venom, this study was done with synthetic herbal compounds, anti PLA2 rabbit antiserum and commercial polyvalent snake venom antiserum to neutralize the PLA2 induced toxicities in experimental models. Methods: B. fasciatus venom phospholipase A2 fraction 38 (BF-38) was isolated by ion exchange chromatography, molecular weight was determined by mass spectrometry and its N terminal amino acid sequence was identified. Monospecific rabbit antiserum was raised against the PLA2 in presence of Freund complete adjuvant. The neutralization of PLA2 induced toxicities was done in in vitro and in in vivo models using synthetic herbal compounds, anti PLA2 rabbit antiserum and commercial polyvalent snake venom antiserum. Results: A toxic PLA2 (BF-38) was purified from the B. fasciatus venom by CM-cellulose and HPLC, of 13.17 kDa and a minor band of 7.3 kDa using ESI-MS. The 13.17 kDa PLA2 sequence was NLYQFKNMIQC. The 7.3 kDa toxin sequence was RKCLTKYSQDNES and was found to be <10 per cent w/w. Anti PLA2 rabbit antiserum produced faint precipitant band in immunogel diffusion and showed low titre value. The commercial polyvalent snake venom antiserum, anti PLA2 rabbit antiserum and the synthetic herbal compounds neutralized the PLA 2 induced toxicities at different intensities. Interpretation & conclusions: Our results suggested that synthetic herbal compound (BA) along with antiserum might provide effective protection against PLA2 induced toxicities of B. fasciatus venom. PMID:22885262

A phase II study of high-dose celecoxib and metronomic 'low-dose' cyclophosphamide and methotrexate in patients with relapsed and refractory lymphoma.

PubMed

El Bary, Naser Abd; Hashem, Tarek; Metwally, Hasan; Ghany, Ashraf Abd; El Mageed, Hager Abd

2010-01-01

Relapsed, histologically aggressive non-Hodgkin lymphoma (NHL) has a poor prognosis; relapsed patients who do not respond to second line therapy or are unfit for BMT have a worse prognosis. Angiogenesis is increased in aggressive NHL and could be targeted by selective cyclooxygenase-2 inhibition and metronomic chemotherapy. We assessed the toxicity of metronomic chemotherapy and the response and progression-free survival in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). We prospectively studied 41 patients with a diagnosis of relapsed and/or refractory DLBCL who may have received any number of preceding therapies (as long as one included an anthracycline) and were not candidates for bone marrow transplantation. They received oral cyclophosphamide (50 mg every day), oral methotrexate (2.5 mg 4 times/week) and high-dose oral celecoxib (400 mg twice daily) until there was disease progression or unacceptable toxicity. All 41 patients (median age, 56 years) were evaluable for toxicity and response, with a median follow up of 9.1 months (range, 4-35 months). At relapse, 51.2% had a high international prognostic index. The treatment protocol was well tolerated with no major toxicities. The most common toxicities were fatigue (61%), nausea (22%), neutropenia (19.5%), and anemia (22%). In 31.7% there was a partial response and 48.8% had stable disease. Progression-free survival was 12 months. The median response duration was 10 months. We conclude that metronomic chemotherapy can be used for patients with relapsed and or refractory DLBCL with reasonable outcome and acceptable toxicity. Standard approaches such as hematopoietic stem cell transplantation and chemo-immunotherapy combinations should be explored prior to a decision on metronomic chemotherapy.

Proton MR Spectroscopy and Diffusion MR Imaging Monitoring to Predict Tumor Response to Interstitial Photodynamic Therapy for Glioblastoma.

PubMed

Toussaint, Magali; Pinel, Sophie; Auger, Florent; Durieux, Nicolas; Thomassin, Magalie; Thomas, Eloise; Moussaron, Albert; Meng, Dominique; Plénat, François; Amouroux, Marine; Bastogne, Thierry; Frochot, Céline; Tillement, Olivier; Lux, François; Barberi-Heyob, Muriel

2017-01-01

Despite recent progress in conventional therapeutic approaches, the vast majority of glioblastoma recur locally, indicating that a more aggressive local therapy is required. Interstitial photodynamic therapy (iPDT) appears as a very promising and complementary approach to conventional therapies. However, an optimal fractionation scheme for iPDT remains the indispensable requirement. To achieve that major goal, we suggested following iPDT tumor response by a non-invasive imaging monitoring. Nude rats bearing intracranial glioblastoma U87MG xenografts were treated by iPDT, just after intravenous injection of AGuIX® nanoparticles, encapsulating PDT and imaging agents. Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) allowed us an original longitudinal follow-up of post-treatment effects to discriminate early predictive markers. We successfully used conventional MRI, T2 star (T2*), Diffusion Weighted Imaging (DWI) and MRS to extract relevant profiles on tissue cytoarchitectural alterations, local vascular disruption and metabolic information on brain tumor biology, achieving earlier assessment of tumor response. From one day post-iPDT, DWI and MRS allowed us to identify promising markers such as the Apparent Diffusion Coefficient (ADC) values, lipids, choline and myoInositol levels that led us to distinguish iPDT responders from non-responders. All these responses give us warning signs well before the tumor escapes and that the growth would be appreciated.

[Characteristics of heritability and effect of selection on prevalence of diffuse-toxic goiter in population].

PubMed

Shtandel', S A; Gopkalova, I V; Khaziev, V V; Dubovik, V N; Svetlova-Kovalenko, E A

2009-01-01

On genealogic data about 242 Gravers disease patients, fertility parameters of 2105 healthy and 369 Grave's disease women peculiarities of genetic determination and natural selection of disease were studied. Results of the genetic analysis have revealed conformity of Grave's disease inheritance to alternative model parameters. Homozygote penetrance within the framework of this model was 78.8%, heterozygote--17.3%. For one generation in the Kharkov area population frequency of a gene to Grave's disease predisposition increases 0.8%.

Cyanide does more to inhibit heme enzymes, than merely serving as an active-site ligand.

PubMed

Parashar, Abhinav; Venkatachalam, Avanthika; Gideon, Daniel Andrew; Manoj, Kelath Murali

2014-12-12

The toxicity of cyanide is hitherto attributed to its ability to bind to heme proteins' active site and thereby inhibit their activity. It is shown herein that the long-held interpretation is inadequate to explain several observations in heme-enzyme reaction systems. Generation of cyanide-based diffusible radicals in heme-enzyme reaction milieu could shunt electron transfers (by non-active site processes), and thus be detrimental to the efficiency of oxidative outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Biocompatibility of composite resins

PubMed Central

Mousavinasab, Sayed Mostafa

2011-01-01

Dental materials that are used in dentistry should be harmless to oral tissues, so they should not contain any leachable toxic and diffusible substances that can cause some side effects. Reports about probable biologic hazards, in relation to dental resins, have increased interest to this topic in dentists. The present paper reviews the articles published about biocompatibility of resin-restorative materials specially resin composites and monomers which are mainly based on Bis-GMA and concerns about their degradation and substances which may be segregated into oral cavity. PMID:23372592

[Megaesophagus in the dog and cat].

PubMed

Mace, S; Shelton, G D; Eddlestone, S

2013-01-01

Megaesophagus is a disorder of the esophagus characterized by diffuse dilation and decreased peristalsis. It is classified into congenital and acquired forms. Gastrointestinal, endocrine, immune-mediated, neuromuscular, paraneoplastic, and toxic disorders have been associated with acquired megaesophagus. Common clinical signs of megaesophagus are regurgitation, weight loss, coughing, and halitosis. Most cases of megaesophagus can be diagnosed using thoracic radiography; however, diagnosing the underlying cause requires a thorough history and additional diagnostics. The treatment, management, and prognosis of megaesophagus vary greatly depending on the underlying cause.

Ocular Toxicity Secondary to Asclepias physocarpa: The Balloon Plant.

PubMed

Pina, Susana; Pedrosa, Catarina; Santos, Cristina; Feijóo, Bernardo; Pego, Peter; Vendrell, Cristina; Santos, Maria João; Prieto, Isabel

2014-01-01

We report a case of a 65-year-old woman with symptoms of blurred vision and ocular irritation a few hours after accidental contact of the right eye with Asclepias physocarpa milky latex. Observation showed a diffuse conjunctival hyperemia and stromal corneal edema with Descemet's membrane folds. Recovery was fast and apparently complete in less than one month. However, specular microscopy at 6-months follow-up showed an abnormal endothelial morphology as sequelae, suggesting this condition is not as innocuous as it has been suggested.

Temperature Variations in Lubricating Films Induced by Viscous Dissipation

NASA Astrophysics Data System (ADS)

Mozaffari, Farshad; Metcalfe, Ralph

2015-11-01

We have studied temperature distributions of lubricating films. The study has applications in tribology where temperature-reduced viscosity decreases load carrying capacity of bearings, or degrades elastomeric seals. The viscosity- temperature dependency is modeled according to ASTM D341-09. We have modeled the film temperature distribution by our finite element program. The program is made up of three modules: the first one solves the general form of Reynolds equation for the film pressure and velocity gradients. The other two solve the energy equation for the film and its solid boundary temperature distributions. The modules are numerically coupled and iteratively converged to the solutions. We have shown that the temperature distribution in the film is strongly coupled with the thermal response at the boundary. In addition, only thermal diffusion across film thickness is dominant. Moreover, thermal diffusion in the lateral directions, as well as all the convection terms, are negligible. The approximation reduces the energy equation to an ordinary differential equation, which significantly simplifies the modeling of temperature -viscosity effects in thin films. Supported by Kalsi Engineering, Inc.

3D patterned stem cell differentiation using thermo-responsive methylcellulose hydrogel molds.

PubMed

Lee, Wonjae; Park, Jon

2016-07-06

Tissue-specific patterned stem cell differentiation serves as the basis for the development, remodeling, and regeneration of the multicellular structure of the native tissues. We herein proposed a cytocompatible 3D casting process to recapitulate this patterned stem cell differentiation for reconstructing multicellular tissues in vitro. We first reconstituted the 2D culture conditions for stem cell fate control within 3D hydrogel by incorporating the sets of the diffusible signal molecules delivered through drug-releasing microparticles. Then, utilizing thermo-responsivity of methylcellulose (MC), we developed a cytocompatible casting process to mold these hydrogels into specific 3D configurations, generating the targeted spatial gradients of diffusible signal molecules. The liquid phase of the MC solution was viscous enough to adopt the shapes of 3D impression patterns, while the gelated MC served as a reliable mold for patterning the hydrogel prepolymers. When these patterned hydrogels were integrated together, the stem cells in each hydrogel distinctly differentiated toward individually defined fates, resulting in the formation of the multicellular tissue structure bearing the very structural integrity and characteristics as seen in vascularized bones and osteochondral tissues.

3D patterned stem cell differentiation using thermo-responsive methylcellulose hydrogel molds

NASA Astrophysics Data System (ADS)

Lee, Wonjae; Park, Jon

2016-07-01

Tissue-specific patterned stem cell differentiation serves as the basis for the development, remodeling, and regeneration of the multicellular structure of the native tissues. We herein proposed a cytocompatible 3D casting process to recapitulate this patterned stem cell differentiation for reconstructing multicellular tissues in vitro. We first reconstituted the 2D culture conditions for stem cell fate control within 3D hydrogel by incorporating the sets of the diffusible signal molecules delivered through drug-releasing microparticles. Then, utilizing thermo-responsivity of methylcellulose (MC), we developed a cytocompatible casting process to mold these hydrogels into specific 3D configurations, generating the targeted spatial gradients of diffusible signal molecules. The liquid phase of the MC solution was viscous enough to adopt the shapes of 3D impression patterns, while the gelated MC served as a reliable mold for patterning the hydrogel prepolymers. When these patterned hydrogels were integrated together, the stem cells in each hydrogel distinctly differentiated toward individually defined fates, resulting in the formation of the multicellular tissue structure bearing the very structural integrity and characteristics as seen in vascularized bones and osteochondral tissues.

3D patterned stem cell differentiation using thermo-responsive methylcellulose hydrogel molds

PubMed Central

Lee, Wonjae; Park, Jon

2016-01-01

Tissue-specific patterned stem cell differentiation serves as the basis for the development, remodeling, and regeneration of the multicellular structure of the native tissues. We herein proposed a cytocompatible 3D casting process to recapitulate this patterned stem cell differentiation for reconstructing multicellular tissues in vitro. We first reconstituted the 2D culture conditions for stem cell fate control within 3D hydrogel by incorporating the sets of the diffusible signal molecules delivered through drug-releasing microparticles. Then, utilizing thermo-responsivity of methylcellulose (MC), we developed a cytocompatible casting process to mold these hydrogels into specific 3D configurations, generating the targeted spatial gradients of diffusible signal molecules. The liquid phase of the MC solution was viscous enough to adopt the shapes of 3D impression patterns, while the gelated MC served as a reliable mold for patterning the hydrogel prepolymers. When these patterned hydrogels were integrated together, the stem cells in each hydrogel distinctly differentiated toward individually defined fates, resulting in the formation of the multicellular tissue structure bearing the very structural integrity and characteristics as seen in vascularized bones and osteochondral tissues. PMID:27381562

Chronomodulation of topotecan or X-radiation treatment increases treatment efficacy without enhancing acute toxicity.

PubMed

Mullins, Dana; Proulx, Denise; Saoudi, A; Ng, Cheng E

2005-05-01

Topotecan (TPT), a camptothecin analog, is currently used to treat human ovarian and small-cell lung cancer and is in clinical trials for other tumor sites. However, it is unknown whether chronomodulation of TPT treatment is beneficial. We examined the effects of administering TPT or X-radiation (XR) alone at different times of the day or night. We treated mice bearing human colorectal tumor xenografts at four different times representing the early rest period (9 am or 3 HALO [hours after light onset]), late rest period (3 pm or 9 HALO), early active period (9 pm or 15 HALO), and late active period (3 am or 21 HALO) of the mice. We gave either TPT (12 mg/kg, injected i.p.) or XR (4 Gy, directed to the tumor) twice weekly on Days 0, 4, 7, 10 within 2 weeks. Treatment with either TPT or XR at 3 am demonstrated the greatest efficacy (measured by a tumor regrowth assay) without significantly increasing acute toxicity (assessed by a decrease in leukocyte counts or body weight). Conversely, treatment at 3 pm, in particular, showed increased toxicity without any enhanced efficacy. Our study provided the first evidence that chronomodulation of TPT treatments, consistent with the findings of other camptothecin analogs, is potentially clinically beneficial. Additionally, our findings suggest that chronomodulation of fractionated XR treatments is also potentially clinically beneficial.

Fluorescence and Magnetic Resonance Dual-Modality Imaging-Guided Photothermal and Photodynamic Dual-Therapy with Magnetic Porphyrin-Metal Organic Framework Nanocomposites

NASA Astrophysics Data System (ADS)

Zhang, Hui; Li, Yu-Hao; Chen, Yang; Wang, Man-Man; Wang, Xue-Sheng; Yin, Xue-Bo

2017-03-01

Phototherapy shows some unique advantages in clinical application, such as remote controllability, improved selectivity, and low bio-toxicity, than chemotherapy. In order to improve the safety and therapeutic efficacy, imaging-guided therapy seems particularly important because it integrates visible information to speculate the distribution and metabolism of the probe. Here we prepare biocompatible core-shell nanocomposites for dual-modality imaging-guided photothermal and photodynamic dual-therapy by the in situ growth of porphyrin-metal organic framework (PMOF) on Fe3O4@C core. Fe3O4@C core was used as T2-weighted magnetic resonance (MR) imaging and photothermal therapy (PTT) agent. The optical properties of porphyrin were well remained in PMOF, and PMOF was therefore selected for photodynamic therapy (PDT) and fluorescence imaging. Fluorescence and MR dual-modality imaging-guided PTT and PDT dual-therapy was confirmed with tumour-bearing mice as model. The high tumour accumulation of Fe3O4@C@PMOF and controllable light excitation at the tumour site achieved efficient cancer therapy, but low toxicity was observed to the normal tissues. The results demonstrated that Fe3O4@C@PMOF was a promising dual-imaging guided PTT and PDT dual-therapy platform for tumour diagnosis and treatment with low cytotoxicity and negligible in vivo toxicity.

Oncolytic Adenovirus Complexes Coated with Lipids and Calcium Phosphate for Cancer Gene Therapy.

PubMed

Chen, Jianhua; Gao, Pei; Yuan, Sujing; Li, Rongxin; Ni, Aimin; Chu, Liang; Ding, Li; Sun, Ying; Liu, Xin-Yuan; Duan, Yourong

2016-12-27

Oncolytic adenovirus (Onco Ad ) is a promising therapeutic agent for treating cancer. However, the therapeutic potential of Onco Ad is hindered by hepatic sequestration and the host immune response in vivo. Here, we constructed a PEG/Lipids/calcium phosphate (CaP)-Onco Ad (PLC-Onco Ad ) delivery system for ZD55-IL-24, an oncolytic adenovirus that carries the IL-24 gene. The negatively charged PLC-ZD55-IL-24 were disperse and resisted serum-induced aggregation. Compared to naked ZD55-IL-24, the systemic administration of PLC-ZD55-IL-24 in BALB/c mice resulted in reduced liver sequestration and systemic toxicity and evaded the innate immune response. In addition, masking the surface of Onco Ad protected it from neutralization by pre-existing neutralizing antibody. PLC-Onco Ad achieved efficient targeted delivery in Huh-7-bearing nude mice, and intravenous administration of a high dose of PLC-ZD55-IL-24 increased therapeutic efficacy without inducing toxicity. The developed PLC-Onco Ad delivery system represents a promising improvement for oncolytic adenovirus-based cancer gene therapy in vivo.

INEL BNCT Research Program Annual Report 1993

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

Venhuizen, J.R.

1994-08-01

This report is a summary of the progress and research produced for the Idaho National Engineering Laboratory Boron Neutron Capture Therapy Research Program for calendar year 1993. Contributions from all the principal investigators are included, covering chemistry (pituitary tumor studies, boron drug development including liposomes, lipoproteins, and carboranylalanine derivatives), pharmacology (murine screenings, toxicity testing, boron drug analysis), physics (radiation dosimetry software, neutron beam and filter design, neutron beam measurement dosimetry), and radiation biology (tissue and efficacy studies of small and large animal models). Information on the potential toxicity of borocaptate sodium and boronophenylalanine is presented. Results of 21 spontaneous-tumor-bearing dogsmore » that have been treated with boron neutron capture therapy at the Brookhaven National Laboratory are updated. Boron-containing drug purity verification is discussed in some detail. Advances in magnetic resonance imaging of boron in vivo are discussed. Several boron-carrying drugs exhibiting good tumor uptake are described. Significant progress in the potential of treating pituitary tumors is presented. Measurement of the epithermal-neutron flux of the Petten (The Netherlands) High Flux Reactor beam (HFB11B), and comparison to predictions are shown.« less

Synergistic effect of sequential administration of mitoguazone (MGBG) and gemcitabine in treating tissue cultured human breast cancer cells and mammary rat tumors.

PubMed

Ishmael, D Richard; Chen, Wei R; Nordquist, John A; Liu, Hong; Nordquist, Robert E

2003-04-01

Modulation of cancer chemotherapeutic drugs has been attempted to increase efficacy and overcome resistance to the chemotherapeutic agent. Studies have shown schedule-dependent interactions in combined use of chemotherapeutic drugs. Mitoguazone (MGBG), an old drug with possible modulating activity, was used in combination with gemcitabine, a relatively new cancer drug, in treating tissue cultured human breast cancer cells and mammary rat tumors. Tissue cultured BOT-2 cancer cells were first treated with varying concentrations of gemcitabine and MGBG, independently. Combinations of the two drugs were then used with different scheduled administrations. Marked synergistic activity was found between gemcitabine and MGBG when the MGBG was given first, followed by gemcitabine 24 hours later. A non-toxic dose of MGBG enhanced the toxicity of gemcitabine by eight orders of magnitude using MTT assays in the tissue cultured human breast cancer cell study. The sequential administration of MGBG and gemcitabine also increased the survival rate of rats bearing mammary tumors in our pilot animal study.

The Tree-Ring Mercury Record of Gold Mining in the Klondike, Central Yukon Territory

NASA Astrophysics Data System (ADS)

Clackett, S.; Porter, T. J.; Lehnherr, I.

2016-12-01

Mercury (Hg) is an atmospherically mixed pollutant of global concern with the potential to become toxic methyl-Hg (MeHg) is some environments. Accurate projections of future health impacts caused by Hg pollution will partly depend on changes in the atmospheric Hg pool, but knowledge of natural Hg variability is limited by a lack of long term monitoring data, which precludes a robust analysis of how it may evolve in the future. Natural archives such as lake sediments, ice cores and tree-rings have the potential to fill this knowledge gap. Tree-rings may be ideally suited for this purpose since they are annually resolved, they span multiple centuries in some areas, and cover large portions of the Earth's surface. Few studies have evaluated tree-ring Hg, and generally agree tree-rings are a passive archive for local Hg emissions. However, further studies are needed to validate this hypothesis. An ideal site to test this proxy is Bear Creek in the Klondike where the Hg amalgamation method was used during the period 1918-1966 to recover fine gold from placer ore. Gaseous Hg was lost to the local environment during operations, as is confirmed by high soil Hg concentrations at the site today. Local trees would have been exposed to the elevated Hg emissions. We measured tree-ring Hg at Bear Creek to determine if historical Hg trends are preserved. Our preliminary results from a single tree reveal that: (1) peak tree-ring Hg coincides with Bear Creek operations; (2) the lowest tree-ring Hg is observed during the pre-industrial control period (1870-1880); and (3) post-Bear Creek operations (1970-2010) coincides with intermediate tree-ring Hg levels, presumably due to higher Hg global backgrounds in recent decades. Additional trees are being analysed to determine if this result is robust, and will provide important insights on the reliability of this proxy for reconstructing long-term atmospheric Hg at local and potentially broader spatial scales.

Loss of radioactivity in radiocesium-bearing microparticles emitted from the Fukushima Dai-ichi nuclear power plant by heating.

PubMed

Okumura, Taiga; Yamaguchi, Noriko; Dohi, Terumi; Iijima, Kazuki; Kogure, Toshihiro

2018-06-26

Radiocesium-bearing microparticles (CsPs) substantially made of silicate glass are a novel form of radiocesium emitted from the broken containment vessel of Fukushima Dai-ichi nuclear power plant. CsPs have a potential risk of internal radiation exposure caused by inhalation. Radiation-contaminated waste including CsPs is being burned in incinerators; therefore, this study has investigated the responses of CsPs to heating in air. The radioactivity of CsPs gradually decreased from 600 °C and was almost lost when the temperature reached 1000 °C. The size and spherical morphology of CsPs were almost unchanged after heating, but cesium including radiocesium, potassium and chlorine were lost, probably diffused away from the CsPs. Iron, zinc and tin originally dissolved in the glass matrix were crystallized to oxide nanoparticles inside the CsPs. When the CsPs were heated together with weathered granitic soil that is common in Fukushima, the radiocesium released from CsPs was sorbed by the surrounding soil. From these results, it is expected that the radioactivity of CsPs will be lost when radiation-contaminated waste including CsPs is burned in incinerators.

Diffuse chorioretinal atrophy after a single standard low- dose intravitreal melphalan injection in a child with retinoblastoma: a case report.

PubMed

Chao, An- Ning; Kao, Ling-Yuh; Liu, Laura; Wang, Nan-Kai

2016-03-15

Controlling retinoblastoma with seeding is challenging despite advances in treatment modalities. Intravitreal melphalan is an alternative to external beam radiation or enucleation for recurrent or refractory vitreous seeds. Significant ocular side effects following intravitreal melphalan injections are uncommon. Complications have been reported in eyes receiving higher concentrations of melphalan and repetitive injections. We report a case in which diffuse chorioretinal atrophy was developed at the injection site after a single, standard low-dose intravitreal melphalan injection. A 12-month-old female child without a family history of retinoblastoma presented with unilateral group C retinoblastoma in her right eye. A solitary tumour with retinal breaks on the tumour surface, and vitreous seeds overlying the tumour were observed at the 8 o'clock position of the retina. After two cycles of intra-arterial chemotherapy with melphalan, the main tumour displayed significant regression, but the vitreous seeds overlying the main tumour were still active. Because of the persistence of vitreous seeds and the inadequate response to intra-arterial melphalan treatment, intravitreal melphalan (8 μg in 0.05 mL) was injected using a 32-gauge needle 2.5 mm from the 5 o'clock position of the limbus, the meridian opposite to the vitreous seeds. After 1 month, the retina around the injection site demonstrated diffuse retinal pigment epithelium alterations with dense hard exudates. Although the main retinal mass, and vitreous seeds resolved, the hard exudates persisted for more than 2 years after the single low-dose melphalan injection. Intravitreal melphalan injections should be cautiously used for eyes with refractory seeds, particularly when multiple injections are required to control retinoblastoma seeds. Dose- related retinal toxicity could occur in pre-treated eyes even when a relatively low standard dose is used. Such patients should be followed up closely to monitor the treatment response and to assess potential delayed toxicity.

Silver nanoparticles induce developmental stage-specific embryonic phenotypes in zebrafish.

PubMed

Lee, Kerry J; Browning, Lauren M; Nallathamby, Prakash D; Osgood, Christopher J; Xu, Xiao-Hong Nancy

2013-12-07

Much is anticipated from the development and deployment of nanomaterials in biological organisms, but concerns remain regarding their biocompatibility and target specificity. Here we report our study of the transport, biocompatibility and toxicity of purified and stable silver nanoparticles (Ag NPs, 13.1 ± 2.5 nm in diameter) upon the specific developmental stages of zebrafish embryos using single NP plasmonic spectroscopy. We find that single Ag NPs passively diffuse into five different developmental stages of embryos (cleavage, early-gastrula, early-segmentation, late-segmentation, and hatching stages), showing stage-independent diffusion modes and diffusion coefficients. Notably, the Ag NPs induce distinctive stage and dose-dependent phenotypes and nanotoxicity, upon their acute exposure to the Ag NPs (0-0.7 nM) for only 2 h. The late-segmentation embryos are most sensitive to the NPs with the lowest critical concentration (CNP,c < 0.02 nM) and highest percentages of cardiac abnormalities, followed by early-segmentation embryos (CNP,c < 0.02 nM), suggesting that disruption of cell differentiation by the NPs causes the most toxic effects on embryonic development. The cleavage-stage embryos treated with the NPs develop into a wide variety of phenotypes (abnormal finfold, tail/spinal cord flexure, cardiac malformation/edema, yolk sac edema, and acephaly). These organ structures are not yet developed in cleavage-stage embryos, suggesting that the earliest determinative events to create these structures are ongoing, and disrupted by NPs, which leads to the downstream effects. In contrast, the hatching embryos are most resistant to the Ag NPs, and majority of embryos (94%) develop normally, and none of them develop abnormally. Interestingly, early-gastrula embryos are less sensitive to the NPs than cleavage and segmentation stage embryos, and do not develop abnormally. These important findings suggest that the Ag NPs are not simple poisons, and they can target specific pathways in development, and potentially enable target specific study and therapy for early embryonic development.

High-dose ifosfamide in combination with etoposide and epirubicin (IVE) in the treatment of relapsed/refractory Hodgkin's disease and non-Hodgkin's lymphoma: a report on toxicity and efficacy.

PubMed

Proctor, S J; Taylor, P R; Angus, B; Wood, K; Lennard, A L; Lucraft, H; Carey, P J; Stark, A; Iqbal, A; Haynes, A; Russel, N; Leonard, R C; Culligan, D; Conn, J; Jackson, G H

2001-07-01

One hundred and seven patients (61 with diffuse large B-cell non-Hodgkin's lymphomas and 46 with Hodgkin's disease) in relapse or following of primary therapy received ifosfamide 3 g/m2 i.v. daily for 3 days in combination with epirubicin 50 mg/m2 i.v. day 1 and etoposide 200 mg/m2 i.v. days 1-3. Of the 46 patients with Hodgkin's disease (28 male, 18 female, and a median age of 28 years) 85% of patients had a response to treatment, with 17 achieving complete remission and 11 good partial remission. Twenty-eight proceeded to autologous bone marrow or peripheral blood stem cell transplantation. Twenty-three patients remain alive in continuous remission with a follow-up of 12-61 months. The median overall survival time for all patients in this group is 36 months. Haematological toxicity, particularly WHO Grade IV neutropenia, occurred in all patients but improved over the three courses of treatment. There was no major non-haematological toxicity. Further trials of this regimen in this clinical situation are indicated. The patients with non-Hodgkin's lymphomas in this study had diffuse large B-cell lymphomas and had only received first-line treatment. Twenty had primarily refractory disease, 15 had only achieved partial remissions (PR), and 26 had developed relapse following primary treatment. The overall response rate was 43%; it was 60% for those who had achieved initial PR, 58% for those in relapse after an initial CR or very good PR following initial therapy, but only 10% for those with primarily refractory disease. Tolerance to the regimen was similar to that observed in treatment of the patients with Hodgkin's disease and many were able to undergo stem cell collection, following mobilization with this regimen. The 2-year overall survival result was 22% for patients with some response to first-line treatment but 0% for primary refractory patients.

Intensity Modulated Radiation Therapy for Early-Stage Primary Gastric Diffuse Large B-Cell Lymphoma: Dosimetric Analysis, Clinical Outcome, and Quality of Life

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

Liu, Xin; Fang, Hui; Tian, Yuan

Purpose: To evaluate the dosimetric superiority, efficacy, toxicity, and quality of life (QOL) data of intensity modulated radiation therapy (IMRT) in patients with primary gastric diffuse large B-cell lymphoma (PG-DLBCL). Methods and Materials: Forty-six consecutive patients with early-stage PG-DLBCL underwent IMRT after chemotherapy. The majority of patients (61.5%) were subclassified as the non-germinal center B cell–like subtype. Dosimetric parameters of the planning target volume (PTV) and organs at risk were assessed. Survival rates were depicted with the Kaplan-Meier method and compared with the log-rank test. Quality of life was evaluated using the QLQ-C30-STO22 questionnaires at the last follow-up contact. Results: Themore » median PTV mean dose was 41.6 Gy. Only 0.73% of the PTV received <95% of the prescribed dose, indicating excellent target coverage. The median kidney V20 and liver V30 were 14.1% and 16.1%, respectively. The 5-year overall survival (OS), progression-free survival, and locoregional control rates for all patients were 80.4%, 75.0%, and 93.2%, respectively. Stage, lactate dehydrogenase level, and immunophenotype were significant prognostic factors for OS, and only stage was a significant factor for locoregional control. Consolidation IMRT in patients with complete response after chemotherapy resulted in significantly better OS and progression-free survival than salvage IMRT in patients with non-complete response. Two of 8 patients who had chronic liver disease experienced grade 4 or grade 5 acute hepatic failure after 4 to 5 cycles of rituximab-based chemotherapy and IMRT (40 Gy). No other serious acute or late toxicity was observed. The long-term global and functional QOL scales were excellent, with negligible symptom scales. Conclusions: Intensity modulated radiation therapy yielded excellent target coverage and critical tissue sparing and achieved favorable outcomes with acceptable toxicity and good long-term QOL in early-stage PG-DLBCL.« less

Enhancing biodegradation of C16-alkyl quaternary ammonium compounds using an oxygen-based membrane biofilm reactor.

PubMed

Lai, YenJung Sean; Ontiveros-Valencia, Aura; Ilhan, Zehra Esra; Zhou, Yun; Miranda, Evelyn; Maldonado, Juan; Krajmalnik-Brown, Rosa; Rittmann, Bruce E

2017-10-15

Quaternary ammonium compounds (QACs) (e.g., hexadecyltrimethyl-ammonium bromide, CTAB) are emerging contaminants with widespread use as surfactants and disinfectants. Because the initial step of QAC biodegradation is mono-oxygenation, QAC degraders require O 2 , but normal aeration leads to serious foaming. Here, we developed and tested an oxygen-based membrane biofilm reactor (O 2 -MBfR) that delivers O 2 by diffusion through the walls of hollow-membranes to a biofilm accumulating on the outer surface of membranes. The O 2 -MBfR sustained QAC biodegradation even with high and toxic QAC input concentrations, up to 400 mg/L CTAB. Bubbleless O 2 transfer completely eliminated foaming, and biofilm accumulation helped the QAC biodegraders resist toxicity. Pseudomonas, Achromobacter, Stenotrophomonas, and members of the Xanthomonadaceae family were dominant in the biofilm communities degrading CTAB, and their proportions depended on the O 2 -delivery capacity of the membranes. Bacteria capable of biodegrading QACs often harbor antibiotic resistance genes (ARGs) that help them avoid QAC toxicity. Gene copies of ARGs were detected in biofilms and liquid, but the levels of ARGs were 5- to 35-fold lower in the liquid than in the biofilm. In summary, the O 2 -MBfR achieved aerobic biodegradation of CTAB with neither foaming nor toxicity, and it also minimized the spread of ARGs. Copyright © 2017 Elsevier Ltd. All rights reserved.