Toxic agent and radiation control: meeting the 1990 objectives for the nation

International Nuclear Information System (INIS)

Rall, D.P.

1984-01-01

Toxic agent and radiation control is 1 of the 15 health priority areas addressed through the Public Health Service's Objectives for the Nation. Several gains in moving toward the 1990 goals for toxic agent and radiation control have been recorded. Research and technical assistance, combined with legislation to reduce the amount of lead in gasoline, have contributed to a decrease in the mean blood lead level of the general population. New testing procedures have been developed to evaluate both reproductive and developmental toxicities of chemicals. Educational implementation of pelvimetry referral criteria in a multiyear study involving approximately 200 U.S. hospitals has resulted in a 50 percent reduction in the number of pelvimetries performed. Health-related responses have been given to environmental problems such as exposures to polychlorinated biphenyls (PCBs) in Massachusetts and Florida and exposures to dioxin in Missouri and New Jersey. Chemical records for some 1000 compounds likely to occur in chemical dumps or in bulk transit are being either created or updated to enhance online data retrieval services. For the foreseeable future, however, improvement of knowledge of the potential health risk posed by toxic chemicals and radiation must remain one of the most important priorities. To control toxic agents, development of surveillance systems and data bases are equally important

SU-F-T-133: Uniform Scanning Proton Therapy for Lung Cancer: Toxicity and Its Correlation with Dosimetry

International Nuclear Information System (INIS)

Zheng, Y; Rana, S; Larson, G

2016-01-01

Purpose: To analyze the toxicity of uniform scanning proton therapy for lung cancer patients and its correlation with dose distribution. Methods: In this study, we analyzed the toxicity of 128 lung cancer patients, including 18 small cell lung cancer and 110 non small cell lung cancer patients. Each patient was treated with uniform scanning proton beams at our center using typically 2–4 fields. The prescription was typically 74 Cobalt gray equivalent (CGE) at 2 CGE per fraction. 4D Computerized Tomography (CT) scans were used to evaluate the target motion and contour the internal target volume, and repeated 3 times during the course of treatment to evaluate the need for plan adaptation. Toxicity data for these patients were obtained from the proton collaborative group (PCG) database. For cases of grade 3 toxicities or toxicities of interest such as esophagitis and radiation dermatitis, dose distributions were reviewed and analyzed in attempt to correlate the toxicity with radiation dose. Results: At a median follow up time of about 21 months, none of the patients had experienced Grade 4 or 5 toxicity. The most common adverse effect was dermatitis (81%: 52%-Grade 1, 28%-Grade 2, and 1% Grade 3), followed by fatigue (48%), Cough (46%), and Esophagitis (45%), as shown in Figure 1. Severe toxicities, such as Grade 3 dermatitis or pain of skin, had a clear correlation with high radiation dose. Conclusion: Uniform scanning proton therapy is well tolerated by lung cancer patients. Preliminary analysis indicates there is correlation between severe toxicity and high radiation dose. Understanding of radiation resulted toxicities and careful choice of beam arrangement are critical in minimizing toxicity of skin and other organs.

SU-F-T-133: Uniform Scanning Proton Therapy for Lung Cancer: Toxicity and Its Correlation with Dosimetry

Energy Technology Data Exchange (ETDEWEB)

Zheng, Y; Rana, S; Larson, G [Procure Proton Therapy Center, Oklahoma City, OK (United States)

2016-06-15

Purpose: To analyze the toxicity of uniform scanning proton therapy for lung cancer patients and its correlation with dose distribution. Methods: In this study, we analyzed the toxicity of 128 lung cancer patients, including 18 small cell lung cancer and 110 non small cell lung cancer patients. Each patient was treated with uniform scanning proton beams at our center using typically 2–4 fields. The prescription was typically 74 Cobalt gray equivalent (CGE) at 2 CGE per fraction. 4D Computerized Tomography (CT) scans were used to evaluate the target motion and contour the internal target volume, and repeated 3 times during the course of treatment to evaluate the need for plan adaptation. Toxicity data for these patients were obtained from the proton collaborative group (PCG) database. For cases of grade 3 toxicities or toxicities of interest such as esophagitis and radiation dermatitis, dose distributions were reviewed and analyzed in attempt to correlate the toxicity with radiation dose. Results: At a median follow up time of about 21 months, none of the patients had experienced Grade 4 or 5 toxicity. The most common adverse effect was dermatitis (81%: 52%-Grade 1, 28%-Grade 2, and 1% Grade 3), followed by fatigue (48%), Cough (46%), and Esophagitis (45%), as shown in Figure 1. Severe toxicities, such as Grade 3 dermatitis or pain of skin, had a clear correlation with high radiation dose. Conclusion: Uniform scanning proton therapy is well tolerated by lung cancer patients. Preliminary analysis indicates there is correlation between severe toxicity and high radiation dose. Understanding of radiation resulted toxicities and careful choice of beam arrangement are critical in minimizing toxicity of skin and other organs.

Seleno methionine-75 as a scanning agent for neuroblastoma

International Nuclear Information System (INIS)

Covington, E.E.; D'Angio, G.J.; Helson, L.; Romano, R.W.

1974-01-01

Neuroblastoma is a functioning tumor and patients with this tumor are known to excrete vanilmandelic acid and other degradation products of norepinephrine. It also accumulates and produces excess cystathionine for which methionine is a precursor in the normal anabolic pathway. This was the rationale for testing 75 Se-methionine as a possible scanning agent in patients with neuroblastoma. D'Angio et al reported the results of a preliminary investigation in which 3 of 4 patients with neuroblastoma, all with known metastases of the skull, had positive scans correctly localizing the disease. These preliminary data seemed encouraging, and further investigation was undertaken. The results are reported

Toxic agents causing cerebellar ataxias.

Science.gov (United States)

Manto, Mario

2012-01-01

The cerebellum is particularly vulnerable to intoxication and poisoning, especially so the cerebellar cortex and Purkinje neurons. In humans, the most common cause of a toxic lesion to the cerebellar circuitry is alcohol related, but the cerebellum is also a main target of drug exposure (such as anticonvulsants, antineoplastics, lithium salts, calcineurin inhibitors), drug abuse and addiction (such as cocaine, heroin, phencyclidine), and environmental toxins (such as mercury, lead, manganese, toluene/benzene derivatives). Although data for the prevalence and incidence of cerebellar lesions related to intoxication and poisoning are still unknown in many cases, clinicians should keep in mind the list of agents that may cause cerebellar deficits, since toxin-induced cerebellar ataxias are not rare in daily practice. Moreover, the patient's status may require immediate therapies when the intoxication is life-threatening. 2012 Elsevier B.V. All rights reserved.

Ecological effects of various toxic agents on the aquatic microcosm in comparison with acute ionizing radiation

International Nuclear Information System (INIS)

Fuma, S.; Ishii, N.; Takeda, H.; Miyamoto, K.; Yanagisawa, K.; Ichimasa, Y.; Saito, M.; Kawabata, Z.; Polikarpov, G.G.

2003-01-01

The purpose of this study was an evaluation of the effect levels of various toxic agents compared with acute doses of ionizing radiation for the experimental model ecosystem, i.e., microcosm mimicking aquatic microbial communities. For this purpose, the authors used the microcosm consisting of populations of the flagellate alga Euglena gracilis as a producer, the ciliate protozoan Tetrahymena thermophila as a consumer and the bacterium Escherichia coli as a decomposer. Effects of aluminum and copper on the microcosm were investigated in this study, while effects of γ-rays, ultraviolet radiation, acidification, manganese, nickel and gadolinium were reported in previous studies. The microcosm could detect not only the direct effects of these agents but also the community-level effects due to the interspecies interactions or the interactions between organisms and toxic agents. The authors evaluated doses or concentrations of each toxic agent which had the following effects on the microcosm: (1) no effects; (2) recognizable effects, i.e., decrease or increase in the cell densities of at least one species; (3) severe effects, i.e., extinction of one or two species; and (4) destructive effects, i.e., extinction of all species. The resulting effects data will contribute to an ecological risk assessment of the toxic agents compared with acute doses of ionizing radiation

Assessment of toxicity on chelating agent DTPA (diethylenetriaminepentaacetic acid)

International Nuclear Information System (INIS)

Fukuda, Satoshi

1989-01-01

DTPA (diethylenetriaminepentaacetic acid) is a very important chelating agent to decorporate the radionuclides such as plutonium and americium from human body. However, before DTPA will be administered to humans, the toxicity should be clarified. This report described the summary on data of DTPA toxicities obtained from animal experiments and assessment on the safety for humans, based on the results that compared their data among animal species. In short, Ca-DTPA is less toxic than Zn-DTPA when it is injected intravenously, while Zn-DTPA is less toxic than Ca-DTPA when it is administered orally. Both DTPAs acted on the serum calcium metabolism and induced the functional damages of cardiovascular system. Particularly, it is stressed that Zn-DTPA by intravenous injection occurred the heart failure, increases of blood pressure and pulse with hypocalcemia in even normal rats and beagle dogs. Other side effects by both DTPAs were also observed in the intestine, liver, kidney and bone. It is estimated that there are almost no species differences on DTPA toxicity between animals and humans. As a result, it is concluded that DTPA should be used very carefully for humans, with reference to the results obtained from animal experiments. (author) 61 refs

Assessment of toxicity on chelating agent DTPA (diethylenetriaminepentaacetic acid)

Energy Technology Data Exchange (ETDEWEB)

Fukuda, Satoshi (National Inst. of Radiological Sciences, Chiba (Japan))

1989-09-01

DTPA (diethylenetriaminepentaacetic acid) is a very important chelating agent to decorporate the radionuclides such as plutonium and americium from human body. However, before DTPA will be administered to humans, the toxicity should be clarified. This report described the summary on data of DTPA toxicities obtained from animal experiments and assessment on the safety for humans, based on the results that compared their data among animal species. In short, Ca-DTPA is less toxic than Zn-DTPA when it is injected intravenously, while Zn-DTPA is less toxic than Ca-DTPA when it is administered orally. Both DTPAs acted on the serum calcium metabolism and induced the functional damages of cardiovascular system. Particularly, it is stressed that Zn-DTPA by intravenous injection occurred the heart failure, increases of blood pressure and pulse with hypocalcemia in even normal rats and beagle dogs. Other side effects by both DTPAs were also observed in the intestine, liver, kidney and bone. It is estimated that there are almost no species differences on DTPA toxicity between animals and humans. As a result, it is concluded that DTPA should be used very carefully for humans, with reference to the results obtained from animal experiments. (author) 61 refs.

Line-scanning confocal microscopy for high-resolution imaging of upconverting rare-earth-based contrast agents

Science.gov (United States)

Higgins, Laura M.; Zevon, Margot; Ganapathy, Vidya; Sheng, Yang; Tan, Mei Chee; Riman, Richard E.; Roth, Charles M.; Moghe, Prabhas V.; Pierce, Mark C.

2015-01-01

Abstract. Rare-earth (RE) doped nanocomposites emit visible luminescence when illuminated with continuous wave near-infrared light, making them appealing candidates for use as contrast agents in biomedical imaging. However, the emission lifetime of these materials is much longer than the pixel dwell times used in scanning intravital microscopy. To overcome this limitation, we have developed a line-scanning confocal microscope for high-resolution, optically sectioned imaging of samples labeled with RE-based nanomaterials. Instrument performance is quantified using calibrated test objects. NaYF4:Er,Yb nanocomposites are imaged in vitro, and in ex vivo tissue specimens, with direct comparison to point-scanning confocal microscopy. We demonstrate that the extended pixel dwell time of line-scanning confocal microscopy enables subcellular-level imaging of these nanomaterials while maintaining optical sectioning. The line-scanning approach thus enables microscopic imaging of this emerging class of contrast agents for preclinical studies, with the potential to be adapted for real-time in vivo imaging in the clinic. PMID:26603495

Toxic agent and radiation control: progress toward objectives for the nation for the year 1990

International Nuclear Information System (INIS)

Rall, D.P.

1988-01-01

In 1980, the Department of Health and Human Services set national prevention objectives for 1990 in 15 health priority areas, 1 of which is the control of toxic agents and radiation. Ten objectives related to this area are priorities for the national control effort. Progress is reviewed on those priorities within the responsibilities of the Public Health Service. Six key program elements, or types of support activities, are deemed essential to preventing, identifying, and controlling toxic agent and radiation threats. Significant progress has been made toward achieving objectives for which all key program elements have been successfully implemented to provide the requisite know-how, manpower, and tools. Important advances have been made in reducing the blood lead levels of the population, reducing unnecessary exposure to medical X-rays, evaluating the toxicities of chemicals in toxic waste dumps, and improving the scientific and technical information base and its availability for prevention and control efforts. The most important priority for the forseeable future will be to expand our knowledge of potential health risks posed by toxic agents and radiation. Expanded surveillance systems and data bases are essential to determining the extent of the problems in terms of human health effects and for measuring the impact of prevention programs. Emphasis on the activities embodied in the key elements will encourage the expansion of the knowledge base and its effective application to prevention and control problems

Stabilized radiographic scanning agents

International Nuclear Information System (INIS)

Fawzi, M.B.

1982-01-01

Stable compositions useful as technetium 99m-based scintigraphic agents comprise gentisic acid or a pharmaceutically-acceptable salt or ester thereof in combination with a pertechnetate reducing agent or dissolved in pertechnetate-99m (sup(99m)TcOsub(4)sup(-)) solution. The compositions are especially useful in combination with a phosphate or phosphonate material that carries the radionuclide to bone, thus providing a skeletal imaging agent

Improved detection and biopsy of solid liver lesions using pulse-inversion ultrasound scanning and contrast agent infusion

DEFF Research Database (Denmark)

Skjoldbye, B.; Pedersen, Morten Høgholm; Struckmann, J.

2002-01-01

The purpose of this study was to assess the ability of pulse-inversion ultrasound (US) scanning (PIUS), combined with an IV contrast agent, to detect malignant liver lesions and its impact on patient management (resectability). Additionally, to determine the feasibility of US-guided biopsy of new...... PIUS-findings at the same session. A total of 30 patients with known or clinically suspected cancer underwent conventional B-mode scanning and PIUS with IV-administered contrast agent. The number of liver metastases in the right and the left liver lobe, respectively, was recorded. All patients...... findings were performed in 17 of 18 patients. All biopsies of additional findings confirmed malignancy. PIUS with an IV contrast agent increased the ability to detect liver metastases compared to conventional US scanning. The technique had a high impact on patient management. The results showed that PIUS...

Ecological effects of ionizing radiation and other toxic agents on the aquatic microcosm

International Nuclear Information System (INIS)

Fuma, Shoichi; Ishii, Nobuyoshi; Tanaka, Nobuyuki; Takeda, Hiroshi; Miyamoto, Kiriko; Yanagisawa, Kei; Kawabata, Zen'ichiro

2004-01-01

The purpose of this study was comparative evaluation of effects of ionizing radiation and other various toxic agents on aquatic microbial communities. For this purpose, the authors investigated effects of γ-rays, ultraviolet (UV) radiation, acidification, aluminum, manganese, nickel, copper and gadolinium on the microcosm, i.e., the experimental model ecosystem consisting of populations of the flagellate alga Euglena gracilis as a producer, the ciliate protozoan Tetrahymena thermophila as a consumer and the bacterium Eseherichia coli as a decomposer. Effects of toxic agents in the microcosm were not only direct effects but also community-level effects due to interactions among the constituting species or between organisms and toxic agents. In general, the degrees of effects observed in the microcosm could be categorized as follows: no effects; recognizable effects, i.e., decrease or increase in the cell densities of at least one species; severe effects, i.e., extinction of one or two species; and destructive effects, i.e., extinction of all species. These results were analyzed by the ecological effect index (EEI), in which differences in the cell densities between exposed and control microcosm were represented by the Euclidean distance function. A 50% effect doses for the microcosm (ED M50 ), at which the EEI became 50%, were evaluated to be 530 Gy for γ-rays, 2100 J m -2 for UV, 4100 μM for manganese, 45 μM for nickel, 110 μM for copper and 250 μM for gadolinium. (author)

Effect of poly-α, γ, L-glutamic acid as a capping agent on morphology and oxidative stress-dependent toxicity of silver nanoparticles

Science.gov (United States)

Stevanović, Magdalena; Kovačević, Branimir; Petković, Jana; Filipič, Metka; Uskoković, Dragan

2011-01-01

Highly stable dispersions of nanosized silver particles were synthesized using a straightforward, cost-effective, and ecofriendly method. Nontoxic glucose was utilized as a reducing agent and poly-α, γ, L-glutamic acid (PGA), a naturally occurring anionic polymer, was used as a capping agent to protect the silver nanoparticles from agglomeration and render them biocompatible. Use of ammonia during synthesis was avoided. Our study clearly demonstrates how the concentration of the capping agent plays a major role in determining the dimensions, morphology, and stability, as well as toxicity of a silver colloidal solution. Hence, proper optimization is necessary to develop silver colloids of narrow size distribution. The samples were characterized by Fourier transform infrared spectroscopy, ultraviolet-visible spectroscopy, field-emission scanning electron microscopy, transmission electron microscopy, and zeta potential measurement. MTT assay results indicated good biocompatibility of the PGA-capped silver nanoparticles. Formation of intracellular reactive oxygen species was measured spectrophotometrically using 2,7-dichlorofluorescein diacetate as a fluorescent probe, and it was shown that the PGA-capped silver nanoparticles did not induce intracellular formation of reactive oxygen species. PMID:22131829

TIC-Tox: A preliminary discussion on identifying the forcing agents of DBP-mediated toxicity of disinfected water.

Science.gov (United States)

Plewa, Michael J; Wagner, Elizabeth D; Richardson, Susan D

2017-08-01

The disinfection of drinking water is a major public health achievement; however, an unintended consequence of disinfection is the generation of disinfection by-products (DBPs). Many of the identified DBPs exhibit in vitro and in vivo toxicity, generate a diversity of adverse biological effects, and may be hazards to the public health and the environment. Only a few DBPs are regulated by several national and international agencies and it is not clear if these regulated DBPs are the forcing agents that drive the observed toxicity and their associated health effects. In this study, we combine analytical chemical and biological data to resolve the forcing agents associated with mammalian cell cytotoxicity of drinking water samples from three cities. These data suggest that the trihalomethanes (THMs) and haloacetic acids may be a small component of the overall cytotoxicity of the organic material isolated from disinfected drinking water. Chemical classes of nitrogen-containing DBPs, such as the haloacetonitriles and haloacetamides, appear to be the major forcing agents of toxicity in these samples. These findings may have important implications for the design of epidemiological studies that primarily rely on the levels of THMs to define DBP exposure among populations. The TIC-Tox approach constitutes a beginning step in the process of identifying the forcing agents of toxicity in disinfected water. Copyright © 2017. Published by Elsevier B.V.

Metal-organic frameworks for the removal of toxic industrial chemicals and chemical warfare agents.

Science.gov (United States)

Bobbitt, N Scott; Mendonca, Matthew L; Howarth, Ashlee J; Islamoglu, Timur; Hupp, Joseph T; Farha, Omar K; Snurr, Randall Q

2017-06-06

Owing to the vast diversity of linkers, nodes, and topologies, metal-organic frameworks can be tailored for specific tasks, such as chemical separations or catalysis. Accordingly, these materials have attracted significant interest for capture and/or detoxification of toxic industrial chemicals and chemical warfare agents. In this paper, we review recent experimental and computational work pertaining to the capture of several industrially-relevant toxic chemicals, including NH 3 , SO 2 , NO 2 , H 2 S, and some volatile organic compounds, with particular emphasis on the challenging issue of designing materials that selectively adsorb these chemicals in the presence of water. We also examine recent research on the capture and catalytic degradation of chemical warfare agents such as sarin and sulfur mustard using metal-organic frameworks.

Antioxidants as potential medical countermeasures for chemical warfare agents and toxic industrial chemicals.

Science.gov (United States)

McElroy, Cameron S; Day, Brian J

2016-01-15

The continuing horrors of military conflicts and terrorism often involve the use of chemical warfare agents (CWAs) and toxic industrial chemicals (TICs). Many CWA and TIC exposures are difficult to treat due to the danger they pose to first responders and their rapid onset that can produce death shortly after exposure. While the specific mechanism(s) of toxicity of these agents are diverse, many are associated either directly or indirectly with increased oxidative stress in affected tissues. This has led to the exploration of various antioxidants as potential medical countermeasures for CWA/TIC exposures. Studies have been performed across a wide array of agents, model organisms, exposure systems, and antioxidants, looking at an almost equally diverse set of endpoints. Attempts at treating CWAs/TICs with antioxidants have met with mixed results, ranging from no effect to nearly complete protection. The aim of this commentary is to summarize the literature in each category for evidence of oxidative stress and antioxidant efficacy against CWAs and TICs. While there is great disparity in the data concerning methods, models, and remedies, the outlook on antioxidants as medical countermeasures for CWA/TIC management appears promising. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of new soil metal immobilizing agents on metal toxicity to terrestrial invertebrates

Energy Technology Data Exchange (ETDEWEB)

Lock, K.; Janssen, C.R

2003-01-01

Organisms with different exposure routes should be used to simultaneously assess risks of metals in soils. - Application of 5% (w:w) novel metal immobilizing agent reduced the water soluble, the calcium chloride extracted as well as the pore water concentration of zinc in soils from Maatheide, a metal contaminated site in the northeast of Belgium. Addition of the metal immobilizing agents also eliminated acute toxicity to the potworm Enchytraeus albidus and the earthworm Eisenia fetida and chronic toxicity to the springtail Folsomia candida. Cocoon production by E. fetida, however, was still adversely affected. These differences may be explained by the species dependent routes of metal uptake: F. candida is probably mainly exposed via pore water while in E. fetida dietary exposure is probably also important. From these results it is clear that organisms with different exposure routes should be used simultaneously to assess the environmental risk of metal contaminated soils.

Stable radiographic scanning agents

International Nuclear Information System (INIS)

1976-01-01

Stable compositions which are useful in the preparation of Technetium-99m-based scintigraphic agents are discussed. They are comprised of ascorbic acid or a pharmaceutically acceptable salt or ester thereof in combination with a pertechnetate reducing agent or dissolved in oxidized pertechnetate-99m (sup(99m)TcO 4 - ) solution

In vitro toxicities of experimental jet fuel system ice-inhibiting agents.

Science.gov (United States)

Geiss, K T; Frazier, J M

2001-07-02

One research emphasis within the Department of Defense has been to seek the replacement of operational compounds with alternatives that pose less potential risk to human and ecological systems. Alternatives to glycol ethers, such as diethylene glycol monomethyl ether (M-DE), were investigated for use as jet fuel system ice-inhibiting agents (FSIIs). This group of chemicals includes three derivatives of 1,3-dioxolane-4-methanol (M-1, M-2, and M-3) and a 1,3-dioxane (M-27). In addition, M-DE was evaluated as a reference compound. Our approach was to implement an in vitro test battery based on primary rat hepatocyte cultures to perform initial toxicity evaluations. Hepatocytes were exposed to experimental chemicals (0, 0.001, 0.01, 0.1, 1, 10 mM dosages) for periods up to 24 h. Samples were assayed for lactate dehydrogenase (LDH) release, MTT dye reduction activity, glutathione level, and rate of protein synthesis as indicators of toxicity. Of the compounds tested, M-1, especially at the 10-mM dose, appeared to be more potent than the other chemicals, as measured by these toxicity assays. M-DE, the current FSII, elicited little response in the toxicity assays. Although some variations in toxicity were observed at the 10-mM dose, the in vitro toxicities of the chemicals tested (except for M-1) were not considerably greater than that of M-DE.

Toxicity and medical countermeasure studies on the organophosphorus nerve agents VM and VX.

Science.gov (United States)

Rice, Helen; Dalton, Christopher H; Price, Matthew E; Graham, Stuart J; Green, A Christopher; Jenner, John; Groombridge, Helen J; Timperley, Christopher M

2015-04-08

To support the effort to eliminate the Syrian Arab Republic chemical weapons stockpile safely, there was a requirement to provide scientific advice based on experimentally derived information on both toxicity and medical countermeasures (MedCM) in the event of exposure to VM, VX or VM-VX mixtures. Complementary in vitro and in vivo studies were undertaken to inform that advice. The penetration rate of neat VM was not significantly different from that of neat VX, through either guinea pig or pig skin in vitro . The presence of VX did not affect the penetration rate of VM in mixtures of various proportions. A lethal dose of VM was approximately twice that of VX in guinea pigs poisoned via the percutaneous route. There was no interaction in mixed agent solutions which altered the in vivo toxicity of the agents. Percutaneous poisoning by VM responded to treatment with standard MedCM, although complete protection was not achieved.

Evaluation of /sup 201/TlCl and delayed scan for thyroid imaging agent

Energy Technology Data Exchange (ETDEWEB)

Taniguchi, Tatsuyoshi; Harada, Taneichi; Takahashi, Tatsuo; Senoo, Tsuneaki; Ohtsuka, Nobuaki; Ito, Yasuhiko [Kawasaki Medical School, Kurashiki, Okayama (Japan)

1982-11-01

The results of 189 patients with nodular goiter by imaging with /sup 201/TlCl following with sup(99m)TcO/sub 4//sup -/ was presented. Accumulation of /sup 201/TlCl to the corresponding area was observed in 85.5% of cancer, 62.2% of adenoma, 42.5% of adenomatous goiter, and the usefulness of /sup 201/TlCl (early scan) for thyroid imaging agent was recognized. On the other hand, delayed scan for purpose of differentiation from benign to malignant was also performed. However, no significant differences were obtained.

Environmental toxicity of Chemical Warfare Agents (CWAs) - MicrotoxTM and Spontaneous Locomotor Changes

DEFF Research Database (Denmark)

Storgaard, Morten Swayne; Sanderson, Hans; Baatrup, Erik

After the 2nd World War the CWAs were prohibited by law and 11,000 tonnes of toxic agents were dumped in the Bornholm Basin east of Bornholm. The dumped chemical munitions have not reached attention from politicians and scientists until recently. During earlier projects, such as MERCW (2005...

Intracellular haemolytic agents of Heterocapsa circularisquama exhibit toxic effects on H. circularisquama cells themselves and suppress both cell-mediated haemolytic activity and toxicity to rotifers (Brachionus plicatilis).

Science.gov (United States)

Nishiguchi, Tomoki; Cho, Kichul; Yasutomi, Masumi; Ueno, Mikinori; Yamaguchi, Kenichi; Basti, Leila; Yamasaki, Yasuhiro; Takeshita, Satoshi; Kim, Daekyung; Oda, Tatsuya

2016-10-01

A harmful dinoflagellate, Heterocapsa circularisquama, is highly toxic to shellfish and the zooplankton rotifer Brachionus plicatilis. A previous study found that H. circularisquama has both light-dependent and -independent haemolytic agents, which might be responsible for its toxicity. Detailed analysis of the haemolytic activity of H. circularisquama suggested that light-independent haemolytic activity was mediated mainly through intact cells, whereas light-dependent haemolytic activity was mediated by intracellular agents which can be discharged from ruptured cells. Because H. circularisquama showed similar toxicity to rotifers regardless of the light conditions, and because ultrasonic ruptured H. circularisquama cells showed no significant toxicity to rotifers, it was suggested that live cell-mediated light-independent haemolytic activity is a major factor responsible for the observed toxicity to rotifers. Interestingly, the ultrasonic-ruptured cells of H. circularisquama suppressed their own lethal effect on the rotifers. Analysis of samples of the cell contents (supernatant) and cell fragments (precipitate) prepared from the ruptured H. circularisquama cells indicated that the cell contents contain inhibitors for the light-independent cell-mediated haemolytic activity, toxins affecting H. circularisquama cells themselves, as well as light-dependent haemolytic agents. Ethanol extract prepared from H. circularisquama, which is supposed to contain a porphyrin derivative that displays photosensitising haemolytic activity, showed potent toxicity to Chattonella marina, Chattonella antiqua, and Karenia mikimotoi, as well as to H. circularisquama at the concentration range at which no significant toxicity to rotifers was observed. Analysis on a column of Sephadex LH-20 revealed that light-dependent haemolytic activity and inhibitory activity on cell-mediated light-independent haemolytic activity existed in two separate fractions (f-2 and f-3), suggesting that both

Development of Tc-99m-DTPA-HSA as a new blood pool scanning agent

Energy Technology Data Exchange (ETDEWEB)

Shirakami, Y; Matsumoto, Y; Yamauchi, Y; Kurami, M; Ueda, N; Hazue, M

1987-04-01

A new HSA preparation, Tc-99m-DTPA-HSA, was developed as a blood pool scanning agent. It shows higher labeling yield (more than 95 %) and higher blood retention (74.7 % I.D. at 1 hour post-injection) than Tc-99m-HSA prepared by directly labeling of HSA with Tc-99m. The introduction of DTPA, a strong bifunctional chelating agent, to HSA provides sites for the stable binding of Tc-99m. The preparation composed of 20 mCi of Tc-99m at calibration time and 10 mg of DTPA-HSA in a vial. After labeling, it had been stable for 24 hours at room temperature. In rats, most of Tc-99m-DTPA-HSA injected was metabolized and excreted in urine and feces. The cumulative radioactivity in urine and feces were 56.0 % and 13.7 % of injected dose, respectively, at 48 hours after injection. Metabolites observed in urine were Tc-99m-urea, Tc-99m-DTPA, reduced Tc-99m and so on. Tc-99m-DTPA-HSA proved, thus, a desirable feature for the blood pool scanning agent.

Technetium-99m labeled radiodiagnostic agents for liver and bone marrow scanning and method of preparation

International Nuclear Information System (INIS)

Molinski, V.J.; Peacock, F.R.

1977-01-01

An improved technetium-99m labeled colloid and method of preparation comprising reducing technetium-99m with stannous oxalate and stabilizing with sodium phytate are described. This radiodiagnostic agent is useful in the scintigraphic examination of the reticuloendothelial system, particularly the liver. In addition, by autoclaving this product with saline, it becomes a superior bone marrow scanning agent

New and superior adrenal scanning agent, NP-59

International Nuclear Information System (INIS)

Sarkar, S.D.; Beierwaltes, W.H.; Ice, R.D.; Basmadjian, G.P.; Hertzel, K.R.; Kennedy, W.P.; Mason, M.M.

1975-01-01

The first synthesis of 131 I-19-iodocholesterol had a 10 to 25 percent radiochemical impurity that was not iodide ion. This impurity has been identified as 6β- 131 I-iodomethyl-19-nor cholest-5(10)-en-3β-ol (NP-59) and has been synthesized. Tissue distribution studies with 131 I-NP-59 in rats and dogs revealed a higher adrenal uptake and adrenal-to-tissue ratios compared to 131 I 19-iodocholesterol, probably less in vivo deiodination, and superior adrenal images. A high uptake was seen in the adrenal medulla in addition to that in the cortex. Iodine-131-NP-59 is being evaluated for the early detection of adrenal--cortical disorders and as a potential scanning agent for detecting structural abnormalities of the adrenal medulla

Preclinical animal acute toxicity studies of new developed MRI contrast agent based on gadolinium

Science.gov (United States)

Nam, I. F.; Zhuk, V. V.

2015-04-01

Acute toxicity test of new developed MRI contrast agent based on disodium salt of gadopentetic acid complex were carried out on Mus musculus and Sprague Dawley rats according to guidelines of preclinical studies [1]. Groups of six animals each were selected for experiment. Death and clinical symptoms of animals were recorded during 14 days. As a result the maximum tolerated dose (MTD) for female mice is 2.8 mM/kg of body weight, male mice - 1.4 mM/kg, female rats - 2.8 mM/kg, male rats - 5.6 mM/kg of body weight. No Observed Adverse Effect Dose (NOAEL) for female mice is 1.4 mM/kg, male mice - 0.7 mM/kg, male and female rats - 0.7 mM/kg. According to experimental data new developed MRI contrast agent based on Gd-DTPA complex is low-toxic.

Radioactive scanning agents with stabilizer

International Nuclear Information System (INIS)

Fawzi, M.B.

1982-01-01

Stable compositions useful as technetium 99-based scintigraphic agents comprise gentisyl alcohol or a pharmaceutically-acceptable salt or ester thereof in combination with a pertechnetate reducing agent or dissolved in pertechnetate-99m (sup(99m)TcOsub(4)sup(-)) solution. The compositions are especially useful in combination with a phosphate or phosphonate material that carries the radionuclide to bone, thus providing a skeletal imaging agent

Chemopreventive agents attenuate rapid inhibition of gap junctional intercellular communication induced by environmental toxicants

Czech Academy of Sciences Publication Activity Database

Babica, Pavel; Čtveráčková, Lucie; Lenčešová, Zuzana; Trosko, J. E.; Upham, B. L.

2016-01-01

Roč. 68, č. 5 (2016), s. 827-837 ISSN 0163-5581 R&D Projects: GA MŠk LH12034 Institutional support: RVO:67985939 Keywords : gap junctional intercellular communication * chemopreventive agents * environmental toxicants Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 2.447, year: 2016

Investigation of Acute Toxicity of a Chemical Warfare Agent in Kidneys

Directory of Open Access Journals (Sweden)

Turgut Topal

2007-08-01

Full Text Available One of the most important chemical warfare agents, sulfur mustard (SM causes crucial acute and chronic toxic effects. Lung, skin, eye and kidneys are the most affected organs. In this work, it was investigated if increased nitric oxide (NO and peroxynitrite are involved in nitrogen mustard (NM induced kidney damage. In this experimen, aminoguanidine (AG as inducible nitric oxide synthase (iNOS inhibitor and ebselen as peroxynitrite scavenger were used. NM administration resulted in important oxidant and antioxidant changes as well as tissue damage in kidneys. Therapeutic agents showed significant protection and reduced oxidant parameteres leading to tissue healing was observed. Results of this study suggest that drugs with similar properties can be used to protect kidney damage caused by NM. [TAF Prev Med Bull. 2007; 6(4: 227-232

Investigation of Acute Toxicity of a Chemical Warfare Agent in Kidneys

Directory of Open Access Journals (Sweden)

Turgut Topal

2007-08-01

Full Text Available One of the most important chemical warfare agents, sulfur mustard (SM causes crucial acute and chronic toxic effects. Lung, skin, eye and kidneys are the most affected organs. In this work, it was investigated if increased nitric oxide (NO and peroxynitrite are involved in nitrogen mustard (NM induced kidney damage. In this experimen, aminoguanidine (AG as inducible nitric oxide synthase (iNOS inhibitor and ebselen as peroxynitrite scavenger were used. NM administration resulted in important oxidant and antioxidant changes as well as tissue damage in kidneys. Therapeutic agents showed significant protection and reduced oxidant parameteres leading to tissue healing was observed. Results of this study suggest that drugs with similar properties can be used to protect kidney damage caused by NM. [TAF Prev Med Bull 2007; 6(4.000: 227-232

Oleuropein, a non-toxic olive iridoid, is an anti-tumor agent and cytoskeleton disruptor

International Nuclear Information System (INIS)

Hamdi, Hamdi K.; Castellon, Raquel

2005-01-01

Oleuropein, a non-toxic secoiridoid derived from the olive tree, is a powerful antioxidant and anti-angiogenic agent. Here, we show it to be a potent anti-cancer compound, directly disrupting actin filaments in cells and in a cell-free assay. Oleuropein inhibited the proliferation and migration of advanced-grade tumor cell lines in a dose-responsive manner. In a novel tube-disruption assay, Oleuropein irreversibly rounded cancer cells, preventing their replication, motility, and invasiveness; these effects were reversible in normal cells. When administered orally to mice that developed spontaneous tumors, Oleuropein completely regressed tumors in 9-12 days. When tumors were resected prior to complete regression, they lacked cohesiveness and had a crumbly consistency. No viable cells could be recovered from these tumors. These observations elevate Oleuropein from a non-toxic antioxidant into a potent anti-tumor agent with direct effects against tumor cells. Our data may also explain the cancer-protective effects of the olive-rich Mediterranean diet

Spot Scanning Proton Therapy for Malignancies of the Base of Skull: Treatment Planning, Acute Toxicities, and Preliminary Clinical Outcomes

Energy Technology Data Exchange (ETDEWEB)

Grosshans, David R., E-mail: dgrossha@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zhu, X. Ronald; Melancon, Adam [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Poenisch, Falk; Palmer, Matthew [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); McAleer, Mary Frances; McGovern, Susan L. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gillin, Michael [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); DeMonte, Franco [Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chang, Eric L. [Department of Radiation Oncology, University of Southern California Keck School of Medicine, Los Angeles, California (United States); Brown, Paul D.; Mahajan, Anita [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2014-11-01

Purpose: To describe treatment planning techniques and early clinical outcomes in patients treated with spot scanning proton therapy for chordoma or chondrosarcoma of the skull base. Methods and Materials: From June 2010 through August 2011, 15 patients were treated with spot scanning proton therapy for chordoma (n=10) or chondrosarcoma (n=5) at a single institution. Toxicity was prospectively evaluated and scored weekly and at all follow-up visits according to Common Terminology Criteria for Adverse Events, version 3.0. Treatment planning techniques and dosimetric data were recorded and compared with those of passive scattering plans created with clinically applicable dose constraints. Results: Ten patients were treated with single-field-optimized scanning beam plans and 5 with multifield-optimized intensity modulated proton therapy. All but 2 patients received a simultaneous integrated boost as well. The mean prescribed radiation doses were 69.8 Gy (relative biological effectiveness [RBE]; range, 68-70 Gy [RBE]) for chordoma and 68.4 Gy (RBE) (range, 66-70) for chondrosarcoma. In comparison with passive scattering plans, spot scanning plans demonstrated improved high-dose conformality and sparing of temporal lobes and brainstem. Clinically, the most common acute toxicities included fatigue (grade 2 for 2 patients, grade 1 for 8 patients) and nausea (grade 2 for 2 patients, grade 1 for 6 patients). No toxicities of grades 3 to 5 were recorded. At a median follow-up time of 27 months (range, 13-42 months), 1 patient had experienced local recurrence and a second developed distant metastatic disease. Two patients had magnetic resonance imaging-documented temporal lobe changes, and a third patient developed facial numbness. No other subacute or late effects were recorded. Conclusions: In comparison to passive scattering, treatment plans for spot scanning proton therapy displayed improved high-dose conformality. Clinically, the treatment was well tolerated, and

Monitoring and Management of Toxicities of Novel B Cell Signaling Agents.

Science.gov (United States)

Rhodes, Joanna; Mato, Anthony; Sharman, Jeff P

2018-04-11

B cell signaling agents, including ibrutinib, idelalisib, and the BCL-2 inhibitor venetoclax have become an integral part of therapy for patients with non-Hodgkin's lymphomas. The toxicity profiles of these medications is distinct from chemoimmunotherapy. Here, we will review the mechanism of action of these drugs, their efficacy, and toxicity management. Ibrutinib use is associated with increased risk of atrial fibrillation and bleeding which can be managed using dose interruptions and modifications. Patients on idelalisib require close clinical and frequent laboratory monitoring, particularly of liver function tests to ensure there are no serious adverse events. Monitoring for infections is important in patients on both idelalisib and ibrutinib. Venetoclax requires close clinical and laboratory monitoring to prevent significant tumor lysis. Targeted B cell receptor therapies each have unique side effect profiles which require careful clinical monitoring. As we continue to use these therapies, optimal management strategies will continue to be elucidated.

Rare earth contrast agents in hepatic computed tomography

International Nuclear Information System (INIS)

Seltzer, S.E.

1981-01-01

Materials with atomic numbers ranging from the upper 50's to the lower 70's proved to have the highest computed tomography (CT) numbers when scanned at 120 kVp. Therefore, to produce particulate contrast agents possessing maximum radiopacity, suspensions of cerium oxide, gadolinium, and dysprosium oxides as well as silver iodide colloid were prepared. All 4 agents were selectively concentrated in the reticulo-endothelial system. The agents produced greater and longer opacification of the normal liver and larger liver-to-tumor differences in rabbits with hepatic tumors than did equivalent amounts of standard intravenous iodinated agents. Lesions as small as 5 mm were visible with CT. These materials have favorable characteristics as hepatic contrast agents, but their toxicity (LD 50 in mice = 5.4 g/kg for Ce) and long-term retention may limit clinical use. (Auth.)

Remediation of toxic ad hazardous wastes: plants as biological agents to mitigate heavy metal pollution

International Nuclear Information System (INIS)

Cadiz, Nina M.; Principe, Eduardo B.

2005-01-01

This papers introduced the plants as biological agents to control heavy metal pollution and the process used the green plants to clean contaminated soils or to render the toxic ions harmless is a new technology called phytoremediation with two levels, the phytostabilization and phytoextraction

Radioactive scanning agents with hydroquinone stabilizer

International Nuclear Information System (INIS)

Whitehouse, H.S.

1982-01-01

Stable compositions useful as technetium 99m-based scintigraphic agents comprise hydroquinone in combination with a pertechnetate reducing agent or dissolved in pertechnetate-99m (sup(99m)TcOsub(4)sup(-)) solution. The compositions are especially useful in combination with a phosphate or phosphonate material which carries the radionuclide to bone, thus providing a skeletal imaging agent

Methodologies for estimating toxicity of shoreline cleaning agents in the field

International Nuclear Information System (INIS)

Clayton, J.R.Jr.; Stransky, B.C.; Schwartz, M.J.; Snyder, B.J.; Lees, D.C.; Michel, J.; Reilly, T.J.

1996-01-01

Four methodologies that could be used in a portable kit to estimate quantitative and qualitative information regarding the toxicity of oil spill cleaning agents, were evaluated. Onshore cleaning agents (SCAs) are meant to enhance the removal of treated oil from shoreline surfaces, and should not increase adverse impacts to organisms in a treated area. Tests, therefore, should be performed with resident organisms likely to be impacted during the use of SCAs. The four methodologies were Microtox T M, fertilization success for echinoderm eggs, byssal thread attachment in mussels, and righting and water-escaping ability in periwinkle snails. Site specific variations in physical and chemical properties of the oil and SCAs were considered. Results were provided, showing all combinations of oils and SCAs. Evaluation showed that all four methodologies provided sufficient information to assist a user in deciding whether or not the use of an SCA was warranted. 33 refs., 7 tabs., 11 figs

Five years audit for presence of toxic agents/drug of abuse at autopsy

International Nuclear Information System (INIS)

Ali, S.M.A.; Khalil, I.R.; Saeed, A.; Hussain, Z.

2003-01-01

Objective: To know the frequency of fatal poisoning in Peshawar regarding the toxic agents mostly involved and year wise percentage. To know the age group and the gender that is most vulnerable to fatal poisoning. Results: Poisoning was the cause of death in 1.48% of the total autopsies conducted during the five years. Males were more involved than the females, 90.38%. Suicidal poisoning was present in 17.30% of the total cases and accidental poisoning was found in 80.72% cases, while homicidal cases were 1.29% only. Diacetylmorphine (heroin) was the most commonly involved agent, 65.38%, of the total cases. The incidence of poisoning was more during the third and fourth decades of life. Conclusion: Diacetylmorphine (heroin) was the main causative agent involved in young males due to accidental over-dosage. Accidental and suicidal deaths should not be considered as inevitable. More elaborative studies are required in this area of recent research to adopt appropriate and adequate measures to save precious lives.(author)

Chemical warfare agent and biological toxin-induced pulmonary toxicity: could stem cells provide potential therapies?

Science.gov (United States)

Angelini, Daniel J; Dorsey, Russell M; Willis, Kristen L; Hong, Charles; Moyer, Robert A; Oyler, Jonathan; Jensen, Neil S; Salem, Harry

2013-01-01

Chemical warfare agents (CWAs) as well as biological toxins present a significant inhalation injury risk to both deployed warfighters and civilian targets of terrorist attacks. Inhalation of many CWAs and biological toxins can induce severe pulmonary toxicity leading to the development of acute lung injury (ALI) as well as acute respiratory distress syndrome (ARDS). The therapeutic options currently used to treat these conditions are very limited and mortality rates remain high. Recent evidence suggests that human stem cells may provide significant therapeutic options for ALI and ARDS in the near future. The threat posed by CWAs and biological toxins for both civilian populations and military personnel is growing, thus understanding the mechanisms of toxicity and potential therapies is critical. This review will outline the pulmonary toxic effects of some of the most common CWAs and biological toxins as well as the potential role of stem cells in treating these types of toxic lung injuries.

Application of Toxic Chinese Medicine in Chinese Pharmacopoeia

Science.gov (United States)

Zhao, Hui; Feng, Yu; Mao, Mingsan

2018-01-01

Objective: Explore the application characteristics of proprietary Chinese medicine prescriptions containing toxic herbs in pharmacopoeia. Methods: In this paper, according to the clinical application of pharmacopoeia proprietary Chinese medicine is divided into table agent, Qushu agent, diarrhea agent, heat agent, Wen Li agent, cough and asthma agents, resuscitation agent, Gutian agent, Fuzheng agent, Anshen agent, hemostatic agent, The traditional Chinese medicine prescription and the clinical application of the Chinese herbal medicine containing the toxic Chinese medicine were analyzed and sorted out., Summed up the compatibility of toxic herbs and application characteristics. Results: Toxic Chinese herbal medicine in the cure of traditional Chinese medicine to play a long-standing role, through the overall thinking, dialectical thinking, and thinking of toxic Chinese medicine in the analysis of Chinese medicine that [2], toxic Chinese medicine in the application of proprietary Chinese medicine can not lack. Conclusion: Pharmacopoeia included proprietary Chinese medicine not only in the clinical treatment of good, but also the application of its toxic traditional Chinese medicine and its understanding of the enrichment of the toxic characteristics of traditional Chinese medicine and treatment-related disease pathology between the points of contact for patients with clinical applications Based on and theoretical guidance of Chinese medicine [3].

Diffusion dynamics and concentration of toxic materials from quantum dots-based nanotechnologies: an agent-based modeling simulation framework

Energy Technology Data Exchange (ETDEWEB)

Agusdinata, Datu Buyung, E-mail: bagusdinata@niu.edu; Amouie, Mahbod [Northern Illinois University, Department of Industrial & Systems Engineering and Environment, Sustainability, & Energy Institute (United States); Xu, Tao [Northern Illinois University, Department of Chemistry and Biochemistry (United States)

2015-01-15

Due to their favorable electrical and optical properties, quantum dots (QDs) nanostructures have found numerous applications including nanomedicine and photovoltaic cells. However, increased future production, use, and disposal of engineered QD products also raise concerns about their potential environmental impacts. The objective of this work is to establish a modeling framework for predicting the diffusion dynamics and concentration of toxic materials released from Trioctylphosphine oxide-capped CdSe. To this end, an agent-based model simulation with reaction kinetics and Brownian motion dynamics was developed. Reaction kinetics is used to model the stability of surface capping agent particularly due to oxidation process. The diffusion of toxic Cd{sup 2+} ions in aquatic environment was simulated using an adapted Brownian motion algorithm. A calibrated parameter to reflect sensitivity to reaction rate is proposed. The model output demonstrates the stochastic spatial distribution of toxic Cd{sup 2+} ions under different values of proxy environmental factor parameters. With the only chemistry considered was oxidation, the simulation was able to replicate Cd{sup 2+} ion release from Thiol-capped QDs in aerated water. The agent-based method is the first to be developed in the QDs application domain. It adds both simplicity of the solubility and rate of release of Cd{sup 2+} ions and complexity of tracking of individual atoms of Cd at the same time.

Diffusion dynamics and concentration of toxic materials from quantum dots-based nanotechnologies: an agent-based modeling simulation framework

International Nuclear Information System (INIS)

Agusdinata, Datu Buyung; Amouie, Mahbod; Xu, Tao

2015-01-01

Due to their favorable electrical and optical properties, quantum dots (QDs) nanostructures have found numerous applications including nanomedicine and photovoltaic cells. However, increased future production, use, and disposal of engineered QD products also raise concerns about their potential environmental impacts. The objective of this work is to establish a modeling framework for predicting the diffusion dynamics and concentration of toxic materials released from Trioctylphosphine oxide-capped CdSe. To this end, an agent-based model simulation with reaction kinetics and Brownian motion dynamics was developed. Reaction kinetics is used to model the stability of surface capping agent particularly due to oxidation process. The diffusion of toxic Cd 2+ ions in aquatic environment was simulated using an adapted Brownian motion algorithm. A calibrated parameter to reflect sensitivity to reaction rate is proposed. The model output demonstrates the stochastic spatial distribution of toxic Cd 2+ ions under different values of proxy environmental factor parameters. With the only chemistry considered was oxidation, the simulation was able to replicate Cd 2+ ion release from Thiol-capped QDs in aerated water. The agent-based method is the first to be developed in the QDs application domain. It adds both simplicity of the solubility and rate of release of Cd 2+ ions and complexity of tracking of individual atoms of Cd at the same time

Non-toxic lead sulfide nanodots as efficient contrast agents for visualizing gastrointestinal tract.

Science.gov (United States)

Liu, Zhen; Ran, Xiang; Liu, Jianhua; Du, Yingda; Ren, Jinsong; Qu, Xiaogang

2016-09-01

Non-invasive imaging of gastrointestinal (GI) tract using novel but efficient contrast agents is of the most important issues in the diagnosis and prognosis of GI diseases. Here, for the first time, we reported the design and synthesis of biothiol-decorated lead sulfide nanodots, as well as their usages in functional dual-modality imaging of GI tract in vivo. Due to the presence of glutathione on the surface of the nanodots, these well-prepared contrast agents could decrease the unwanted ion leakage, withstand the harsh conditions in GI tract, and avoid the systemic absorption after oral administration. Compared with clinical barium meal and iodine-based contrast agents, these nanodots exhibited much more significant enhancement in contrast efficiency during both 2D X-ray imaging and 3D CT imaging. Different from some conventional invasive imaging modalities, such as gastroscope and enteroscope, non-invasive imaging strategy by using glutathione modified PbS nanodots as contrast agents could reduce the painfulness towards patients, facilitate the imaging procedure, and economize the manipulation period. Moreover, long-term toxicity and bio-distribution of these nanodots after oral administration were evaluated in detail, which indicated their overall safety. Based on our present study, these nanodots could act as admirable contrast agents to integrate X-ray imaging and CT imaging for the direct visualization of GI tract. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fate of chemical warfare agents and toxic industrial chemicals in landfills.

Science.gov (United States)

Bartelt-Hunt, Shannon L; Barlaz, Morton A; Knappe, Detlef R U; Kjeldsen, Peter

2006-07-01

One component of preparedness for a chemical attack is planning for the disposal of contaminated debris. To assess the feasibility of contaminated debris disposal in municipal solid waste (MSW) landfills, the fate of selected chemical warfare agents (CWAs) and toxic industrial chemicals (TICs) in MSW landfills was predicted with a mathematical model. Five blister agents [sulfur mustard (HD), nitrogen mustard (HN-2), lewisite (L), ethyldichloroarsine (ED), and phosgene oxime (CX)], eight nerve agents [tabun (GA), sarin (GB), soman (GD), GE, GF, VX, VG, and VM], one riot-control agent [CS], and two TICs [furan and carbon disulfide] were studied. The effects of both infiltration (climate) and contaminant biodegradability on fate predictions were assessed. Model results showed that hydrolysis and gas-phase advection were the principal fate pathways for CWAs and TICs, respectively. Apart from CX and the TICs, none of the investigated compounds was predicted to persist in a landfill for more than 5 years. Climate had little impact on CWA/TIC fate, and biodegradability was only important for compounds with long hydrolysis half-lives. Monte Carlo simulations were performed to assess the influence of uncertainty in model input parameters on CWA/TIC fate predictions. Correlation analyses showed that uncertainty in hydrolysis rate constants was the primary contributor to variance of CWA fate predictions, while uncertainty in the Henry's Law constant and landfill gas-production rate accounted for most of the variance of TIC fate predictions. CWA hydrolysates were more persistent than the parent CWAs, but limited information is available on abiotic or biotic transformation rates for these chemicals.

Pharmacophore modeling and in silico toxicity assessment of potential anticancer agents from African medicinal plants.

Science.gov (United States)

Ntie-Kang, Fidele; Simoben, Conrad Veranso; Karaman, Berin; Ngwa, Valery Fuh; Judson, Philip Neville; Sippl, Wolfgang; Mbaze, Luc Meva'a

2016-01-01

Molecular modeling has been employed in the search for lead compounds of chemotherapy to fight cancer. In this study, pharmacophore models have been generated and validated for use in virtual screening protocols for eight known anticancer drug targets, including tyrosine kinase, protein kinase B β, cyclin-dependent kinase, protein farnesyltransferase, human protein kinase, glycogen synthase kinase, and indoleamine 2,3-dioxygenase 1. Pharmacophore models were validated through receiver operating characteristic and Güner-Henry scoring methods, indicating that several of the models generated could be useful for the identification of potential anticancer agents from natural product databases. The validated pharmacophore models were used as three-dimensional search queries for virtual screening of the newly developed AfroCancer database (~400 compounds from African medicinal plants), along with the Naturally Occurring Plant-based Anticancer Compound-Activity-Target dataset (comprising ~1,500 published naturally occurring plant-based compounds from around the world). Additionally, an in silico assessment of toxicity of the two datasets was carried out by the use of 88 toxicity end points predicted by the Lhasa's expert knowledge-based system (Derek), showing that only an insignificant proportion of the promising anticancer agents would be likely showing high toxicity profiles. A diversity study of the two datasets, carried out using the analysis of principal components from the most important physicochemical properties often used to access drug-likeness of compound datasets, showed that the two datasets do not occupy the same chemical space.

Chemical and biological properties of toxic metals and use of chelating agents for the pharmacological treatment of metal poisoning

Energy Technology Data Exchange (ETDEWEB)

Sinicropi, Maria Stefania; Caruso, Anna [University of Calabria, Department of Pharmaceutical Sciences, Rende (Italy); Amantea, Diana [University of Calabria, Department of Pharmacobiology, Rende (Italy); Saturnino, Carmela [University of Salerno, Department of Pharmaceutical Sciences, Fisciano (Italy)

2010-07-15

Exposure to toxic metals is a well-known problem in industrialized countries. Metals interfere with a number of physiological processes, including central nervous system (CNS), haematopoietic, hepatic and renal functions. In the evaluation of the toxicity of a particular metal it is crucial to consider many parameters: chemical forms (elemental, organic or inorganic), binding capability, presence of specific proteins that selectively bind metals, etc. Medical treatment of acute and chronic metal toxicity is provided by chelating agents, namely organic compounds capable of interacting with metal ions to form structures called chelates. The present review attempts to provide updated information about the mechanisms, the cellular targets and the effects of toxic metals. (orig.)

99mTc bone scanning agents preparation and chemical analysis of Tc(Sn)pyrophosphate, Tc(Sn)MDP and Tc(Sn)HMDP

International Nuclear Information System (INIS)

Kroesbergen, J.

1986-01-01

This thesis describes a comparison of the preparation, composition and properties of three bone scanning agents: 99m Tc(Sn)pyrophosphate, 99m Tc(Sn)MDP and 99m Tc(Sn)HMDP. This study has been performed for two reasons: First to investigate the preparation and composition of the radiopharmaceuticals as a function of experimental conditions. Together with previously reported results for 99m Tc(Sn)EHDP, obtained in a similar way, this enables to use well-defined preparations of the bone scanning agents. Secondly to gain an insight in the mechanism in which the agents behave 'in vivo'. Because the 'in vivo' process is too complicated to study directly, it seemed more appropriate to perform 'in vitro' investigations as simplifications of the 'in vivo' situation. 304 refs.; 26 figs.; 31 tabs

Radionuclide scanning

International Nuclear Information System (INIS)

Shapiro, B.

1986-01-01

Radionuclide scanning is the production of images of normal and diseased tissues and organs by means of the gamma-ray emissions from radiopharmaceutical agents having specific distributions in the body. The gamma rays are detected at the body surface by a variety of instruments that convert the invisible rays into visible patterns representing the distribution of the radionuclide in the body. The patterns, or images, obtained can be interpreted to provide or to aid diagnoses, to follow the course of disease, and to monitor the management of various illnesses. Scanning is a sensitive technique, but its specificity may be low when interpreted alone. To be used most successfully, radionuclide scanning must be interpreted in conjunction with other techniques, such as bone radiographs with bone scans, chest radiographs with lung scans, and ultrasonic studies with thyroid scans. Interpretation is also enhanced by providing pertinent clinical information because the distribution of radiopharmaceutical agents can be altered by drugs and by various procedures besides physiologic and pathologic conditions. Discussion of the patient with the radionuclide scanning specialist prior to the study and review of the results with that specialist after the study are beneficial

Possible inclinations for psychostimulant, toxic agent and drug abuse among youths and students

Directory of Open Access Journals (Sweden)

V. G. Ginzburg

2012-03-01

Full Text Available Taking into account modern achievements in medicine, psychology and sociology, the attempt at complex research of possible inclinations for psychostimulant, toxic agent and drug abuse among youths and students was made with the subsequent determination of the possible alternates of primary prevention. It is analysed the basic and additional risk factors promoting smoking, drinking, psychostimulant abuse, toxicomania and narcomania among young people. The dynamics of possible influences of medical, psychological and social factors is studied. The attempt of short-term prognostication and ranking was made.

A study on the influence of surface active agent molecules on the AFM scanning and imaging of SWCNTs

Energy Technology Data Exchange (ETDEWEB)

Xu Ke; Yu Haibo; Tian Xiaojun; Dong Zaili [State Key Laboratory of Robotics, Shenyang Institute of Automation, CAS, Shenyang 110016 (China); Wu Chengdong [Northeastern University, Shenyang 110004 (China)], E-mail: xuke08@sia.cn

2009-09-01

The paper proposed a preprocessing method for scanning samples based on rinsing technology, and solved the effective fabrication problem of AFM scanning samples based on facilitated dispersing SWCNTs with SDS surface active agents. First, the ultrasonication oscillation method was applied, and the uniform alignment of SWCNTs in SDS was realized. Then, SDS solution of different concentrations was scanned and imaged with AFM, the influence of SDS solution on the imaging quality of SWCNTs was analyzed, and the method to effectively fabricate scanning samples after dispersing SWCNTs was found. The results of the experiments showed that the preprocessing of the SWCNTs solution scanning samples was the decisive factor to influence SWCNTs imaging quality, that the result of rinsing SWCNTs scanning samples for 5s at 0.1ml/s with di-ionized water was the best, and that with the same rinsing rate and angle, the rinsing di-ionized water quantity would influence the alignment degree of SWCNTs on the substrates and SDS macromolecules' residual quantity on SWCNTs scanning samples.

Effect of poly-α, γ, L-glutamic acid as a capping agent on morphology and oxidative stress-dependent toxicity of silver nanoparticles

Directory of Open Access Journals (Sweden)

Stevanović M

2011-11-01

Full Text Available Magdalena Stevanović1, Branimir Kovačević2, Jana Petković3, Metka Filipič3, Dragan Uskoković11Institute of Technical Sciences of Serbian Academy of Sciences and Arts, 2Institute of General and Physical Chemistry, Belgrade, Serbia; 3Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ljubljana, SloveniaAbstract: Highly stable dispersions of nanosized silver particles were synthesized using a straightforward, cost-effective, and ecofriendly method. Nontoxic glucose was utilized as a reducing agent and poly- α, γ, L-glutamic acid (PGA, a naturally occurring anionic polymer, was used as a capping agent to protect the silver nanoparticles from agglomeration and render them biocompatible. Use of ammonia during synthesis was avoided. Our study clearly demonstrates how the concentration of the capping agent plays a major role in determining the dimensions, morphology, and stability, as well as toxicity of a silver colloidal solution. Hence, proper optimization is necessary to develop silver colloids of narrow size distribution. The samples were characterized by Fourier transform infrared spectroscopy, ultraviolet-visible spectroscopy, field-emission scanning electron microscopy, transmission electron microscopy, and zeta potential measurement. MTT assay results indicated good biocompatibility of the PGA-capped silver nanoparticles. Formation of intracellular reactive oxygen species was measured spectrophotometrically using 2,7-dichlorofluorescein diacetate as a fluorescent probe, and it was shown that the PGA-capped silver nanoparticles did not induce intracellular formation of reactive oxygen species.Keywords: silver nanoparticles, poly-α, γ, L-glutamic, green synthesis, morphology, cytotoxicity

Comparison of feeding strategies in acute toxicity tests of crude oil and commercial bioremediation agents

International Nuclear Information System (INIS)

Cavender, R.C.; Cherry, D.S.; Yeager, M.M.; Bidwell, J.R.

1995-01-01

Proposed modifications to the National Oil and Hazardous Substance Pollution Contingency Plan have prompted examinations of the methodology used in toxicity testing of the water soluble fraction (WSF) of oil, commercial bioremediation agents (CBA), and a combination of the two. The organisms currently used in acute (96 hr) testing of these agents are the inland silverside, Menidia beryllina, and an estuarine mysid, Mysidopsis bahia. The mysid is a carnivorous species that must be fed during a test in order to prevent predation within the test chambers. Currently proposed methodology for silverside testing also includes feeding. The high oxygen demand of CBAs and the WSF of oil causes dissolved oxygen to be a factor in toxicity. This effect can be intensified by the addition of brine shrimp (Artemia sp.) to the test chambers. The purpose of this study was to compare the toxicity of CBAs in combination with the WSF of oil to silversides with and without the addition of food. Tests were conducted using both 24-hour and 14-day spinning times for the CBA/WSF mixture. With the 24-hour spinning time, LC50 values from each day of the 4-day test were consistently lower in the Artemia fed test (47.8--22.6%) as compared to the unfed test (72.1--43.0%). A similar trend was seen in the 24 and 48 hour LC50's in the 14-day spinning time. Overall, low dissolved oxygen was found to be most relevant at the highest CBA/WSF concentrations where D.O. dropped below 2 mg/l in Artemia fed tests

Gadolinium-based contrast agent toxicity: a review of known and proposed mechanisms.

Science.gov (United States)

Rogosnitzky, Moshe; Branch, Stacy

2016-06-01

Gadolinium chelates are widely used as contrast media for magnetic resonance imaging. The approved gadolinium-based contrast agents (GBCAs) have historically been considered safe and well tolerated when used at recommended dosing levels. However, for nearly a decade, an association between GBCA administration and the development of nephrogenic systemic fibrosis (NSF) has been recognized in patients with severe renal impairment. This has led to modifications in clinical practices aimed at reducing the potential and incidence of NSF development. Newer reports have emerged regarding the accumulation of gadolinium in various tissues of patients who do not have renal impairment, including bone, brain, and kidneys. Despite the observations of gadolinium accumulation in tissues regardless of renal function, very limited clinical data regarding the potential for and mechanisms of toxicity is available. This significant gap in knowledge warrants retrospective cohort study efforts, as well as prospective studies that involve gadolinium ion (Gd(3+)) testing in patients exposed to GBCA. This review examines the potential biochemical and molecular basis of gadolinium toxicity, possible clinical significance of gadolinium tissue retention and accumulation, and methods that can limit gadolinium body burden.

MR brain scan tissues and structures segmentation: local cooperative Markovian agents and Bayesian formulation

International Nuclear Information System (INIS)

Scherrer, B.

2008-12-01

Accurate magnetic resonance brain scan segmentation is critical in a number of clinical and neuroscience applications. This task is challenging due to artifacts, low contrast between tissues and inter-individual variability that inhibit the introduction of a priori knowledge. In this thesis, we propose a new MR brain scan segmentation approach. Unique features of this approach include (1) the coupling of tissue segmentation, structure segmentation and prior knowledge construction, and (2) the consideration of local image properties. Locality is modeled through a multi-agent framework: agents are distributed into the volume and perform a local Markovian segmentation. As an initial approach (LOCUS, Local Cooperative Unified Segmentation), intuitive cooperation and coupling mechanisms are proposed to ensure the consistency of local models. Structures are segmented via the introduction of spatial localization constraints based on fuzzy spatial relations between structures. In a second approach, (LOCUS-B, LOCUS in a Bayesian framework) we consider the introduction of a statistical atlas to describe structures. The problem is reformulated in a Bayesian framework, allowing a statistical formalization of coupling and cooperation. Tissue segmentation, local model regularization, structure segmentation and local affine atlas registration are then coupled in an EM framework and mutually improve. The evaluation on simulated and real images shows good results, and in particular, a robustness to non-uniformity and noise with low computational cost. Local distributed and cooperative MRF models then appear as a powerful and promising approach for medical image segmentation. (author)

Fate of chemical warfare agents and toxic indutrial chemicals in landfills

DEFF Research Database (Denmark)

Bartelt-Hunt, D.L.; Barlaz, M.A.; Knappe, D.R.U.

2006-01-01

One component of preparedness for a chemical attack is planning for the disposal of contaminated debris. To assess the feasibility of contaminated debris disposal in municipal solid waste (MSW) landfills, the fate of selected chemical warfare agents (CWAs) and toxic industrial chemicals (TICs......], and two TICs [furan and carbon disulfide] were studied. The effects of both infiltration (climate) and contaminant biodegradability on fate predictions were assessed. Model results showed that hydrolysis and gas-phase advection were the principal fate pathways for CWAs and TICs, respectively. Apart from...... CX and the TICs, none of the investigated compounds was predicted to persist in a landfill for more than 5 years. Climate had little impact on CWA/TIC fate, and biodegradability was only important for compounds with long hydrolysis halflives. Monte Carlo simulations were performed to assess...

Evaluation of optimized magnetic resonance perfusion imaging scanning time window after contrast agent injection for differentiating benign and malignant breast lesions.

Science.gov (United States)

Dong, Jie; Wang, Dawei; Ma, Zhenshen; Deng, Guodong; Wang, Lanhua; Zhang, Jiandong

2017-03-01

The aim of the study was evaluate the 3.0 T magnetic resonance (MR) perfusion imaging scanning time window following contrast injection for differentiating benign and malignant breast lesions and to determine the optimum scanning time window for increased scanner usage efficiency and reduced diagnostic adverse risk factors. A total of 52 women with breast abnormalities were selected for conventional MR imaging and T1 dynamic-enhanced imaging. Quantitative parameters [volume transfer constant (K trans ), rate constant (K ep ) and extravascular extracellular volume fraction (V e )] were calculated at phases 10, 20, 30, 40 and 50, which represented time windows at 5, 10, 15, 20 and 25 min, respectively, following injection of contrast agent. The association of the parameters at different phases with benign and malignant tumor diagnosis was analyzed. MR perfusion imaging was verified as an effective modality in the diagnosis of breast malignancies and the best scanning time window was identified: i) Values of K trans and K ep at all phases were statistically significant in differentiating benign and malignant tumors (P0.05); ii) values of V e in benign tumors increased with phase number, but achieved no obvious changes at different phases in malignant tumors; iii) the optimum scanning time window of breast perfusion imaging with 3.0 T MR was between phases 10 and 30 (i.e., between 5 and 15 min after contrast agent injection). The variation trend of V e values at different phases may serve as a diagnostic reference for differentiating benign and malignant breast abnormalities. The most efficient scanning time window was indicated to be 5 min after contrast injection, based on the observation that the V e value only had statistical significance in diagnosis at stage 10. However, the optimal scanning time window is from 5 to 15 min following the injection of contrast agent, since that the variation trend of V e is able to serve as a diagnostic reference.

Insect-gene-activity detection system for chemical and biological warfare agents and toxic industrial chemicals

Science.gov (United States)

Mackie, Ryan S.; Schilling, Amanda S.; Lopez, Arturo M.; Rayms-Keller, Alfredo

2002-02-01

Detection of multiple chemical and biological weapons (CBW) agents and/or complex mixtures of toxic industrial chemicals (TIC) is imperative for both the commercial and military sectors. In a military scenario, a multi-CBW attack would create confusion, thereby delaying decontamination and therapeutic efforts. In the commercial sector, polluted sites invariably contain a mixture of TIC. Novel detection systems capable of detecting CBW and TIC are sorely needed. While it may be impossible to build a detector capable of discriminating all the possible combinations of CBW, a detection system capable of statistically predicting the most likely composition of a given mixture is within the reach of current emerging technologies. Aquatic insect-gene activity may prove to be a sensitive, discriminating, and elegant paradigm for the detection of CBW and TIC. We propose to systematically establish the expression patterns of selected protein markers in insects exposed to specific mixtures of chemical and biological warfare agents to generate a library of biosignatures of exposure. The predicting capabilities of an operational library of biosignatures of exposures will allow the detection of emerging novel or genetically engineered agents, as well as complex mixtures of chemical and biological weapons agents. CBW and TIC are discussed in the context of war, terrorism, and pollution.

Detecting the effects of toxic agents on spermatogenesis using DNA probes

International Nuclear Information System (INIS)

Hecht, N.B.

1987-01-01

Advances in the molecular biology of spermatogenesis suggest that DNA probes can be used to monitor the effects of toxic agents in male germ cells of mammals. Molecular hybridization analyses with DNA probes can provide a reproducible methodology capable of detecting changes ranging from massive deletions to single base pair substitutions in the genome of exposed individuals. A constantly increasing number of DNA probes that can be used to detect such alterations in human sperm DNA exist for both ubiquitously expressed proteins and for genes solely expressed in the testis. In this chapter, the currently available testicular stage-specific and/or cell type-specific DNA probes and the techniques by which they can be utilized in reproductive toxicology studies are discussed. The advantages, limitations, and future technological advances of this novel biological marker system for the human male reproductive system are also considered

Overview of shoreline cleaning agents

International Nuclear Information System (INIS)

Clayton, J.

1992-01-01

Chemical cleaning agents may be used to promote release of stranded oil from shorelines for reasons including biological sensitivity of indigenous fauna and flora to the oil, amenity considerations of the shoreline, or concern about refloating of the oil and subsequent stranding on adjacent shorelines. While use of chemical cleaning agents may be appropriate under proper toxic responses in circumstances, certain limitations should be recognized. The potential for toxic responses in indigenous fauna and flora to the cleaning agents must be considered. Enhanced penetration of oil into permeable shorelines following treatment with chemical cleaning agents also is not desirable. However, if conditions related to toxicity and substrate permeability are determined to be acceptable, the use of chemical cleaning agents for treatment of stranded oil can be considered. Chemical agents for cleaning oiled shorelines can be grouped into three categories: (1) non-surfactant-based solvents, (2) chemical dispersants, and (3) formulations especially designed to release stranded oil from shoreline substrates (i.e., shoreline-cleaning-agents). Depending on the specific circumstances present on an oiled shoreline, it is generally desirable that chemical agents used for cleaning will release oil from shoreline substrate(s) to surface waters. Recovery of the oil can then be accomplished by mechanical procedures such as booming and skimming operations

Toxicity induced by chemical warfare agents: insights on the protective role of melatonin.

Science.gov (United States)

Pita, René; Marco-Contelles, José; Ramos, Eva; Del Pino, Javier; Romero, Alejandro

2013-11-25

Chemical Warfare Agents (CWAs) are substances that can be used to kill, injure or incapacitate an enemy in warfare, but also against civilian population in terrorist attacks. Many chemical agents are able to generate free radicals and derived reactants, excitotoxicity process, or inflammation, and as consequence they can cause neurological symptoms and damage in different organs. Nowadays, taking into account that total immediate decontamination after exposure is difficult to achieve and there are not completely effective antidotes and treatments against all CWAs, we advance and propose that medical countermeasures against CWAs poisoning would benefit from a broad-spectrum multipotent molecule. Melatonin, a versatile and ubiquitous antioxidant molecule, originally discovered as a hormone synthesized mainly in the pineal gland, has low toxicity and high efficacy in reducing oxidative damage, anti-inflammatory effects by regulation of multiple cellular pathways and properties to prevent excitotoxicity, among others. The purpose of this review is to show the multiple and diverse properties of melatonin, as a pleiotropic indole derivative, and its marked potential for improving human health against the most widely used chemical weapons. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Frequency and impact of grade three or four toxicities of novel agents on outcomes of older patients with chronic lymphocytic leukemia and non-Hodgkin lymphoma (alliance A151611).

Science.gov (United States)

Tallarico, Michael; Foster, Jared C; Seisler, Drew; Lafky, Jacqueline M; Hurria, Arti; Jatoi, Aminah; Cohen, Harvey J; Muss, Hyman B; Bartlett, Nancy; Cheson, Bruce D; Jung, Sin-Ho; Leonard, John P; Byrd, John C; Nabhan, Chadi

2018-04-16

Older patients with cancer suffer from chemotherapy-related toxicities more frequently than younger patients. As novel agents are being used more commonly in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), toxicities of these agents in older patients have not been well studied. Further, impact of these toxicities on outcomes in the elderly is unknown. This study aimed to answer both questions. We reviewed 14 Alliance for Clinical Trials in Oncology trials that enrolled CLL and/or NHL patients between 2004-2014. Toxicity was assessed per the NCI-CTCAE (version 3-5). Probabilities of experiencing grade three or four hematologic and non-hematologic toxicities were modeled as a function of clinical and disease-related factors using logistic regression. 1199 patients (409 age ≥ 65; 790 age four hematologic [odds ratio (OR) 1.70; p = 0.009: 95% CI (1.57-1.84)] and non-hematologic toxicities [OR 1.47; p = 0.022; 95% CI (1.39-1.55)] were increased in older patients with CLL, as well as odds of grade three or four non-hematologic toxicities [OR 1.89; p = 0.017; 95% CI (1.64-2.17)] in older patients with NHL. Grade three or four hematologic toxicities were associated with inferior OS and PFS in older patients with NHL [HR 3.14; p = 0.006; 95% CI (2.25-4.39) for OS and 3.06; p = 0.011; 95% CI (2.10-4.45) for PFS], though not in CLL. A prognostic model predicting grade three or four toxicities was also developed. CLL and NHL patients ≥ 65 year encounter more toxicities than younger patients even when treated with novel biologic agents. Development of grade three or four hematologic toxicities lead to inferior PFS and OS in NHL but not in CLL. Copyright © 2018 Elsevier Inc. All rights reserved.

Tavaborole, a Novel Boron-Containing Small Molecule Pharmaceutical Agent for Topical Treatment of Onychomycosis: I. Reproductive and Developmental Toxicity Studies.

Science.gov (United States)

Ciaravino, Vic; Coronado, Dina; Lanphear, Cheryl; Hoberman, Alan; Chanda, Sanjay

2016-09-01

Tavaborole is a topical antifungal agent approved by the US Food and Drug Administration for the treatment of toenail onychomycosis. As part of the nonclinical development program, reproductive and developmental toxicity studies were conducted (rat oral fertility and early embryonic development, rat (oral) and rabbit (dermal) embryo-fetal development). There were no effects on fertility or reproductive performance at doses up to 300 mg/kg/d (107 times the maximum recommended human dose [MRHD] based on mean area under the plasma concentration-time curve comparisons). In the rat embryo-fetal development toxicity studies, teratogenicity was not observed at doses up to 100 mg/kg/d (29 times the MRHD). However, several treatment-related skeletal malformations and variations were observed at 300 mg/kg/d (570 times the MRHD). In rabbit embryo-fetal development toxicity studies dosed via oral or dermal administration, the no observable adverse effect level for maternal toxicity and embryo-fetal toxicity was 50 mg/kg/d (16 times the MRHD) and 5% (26 times the MRHD), respectively. © The Author(s) 2016.

Synthesis of microcapsules containing different extractant agents.

Science.gov (United States)

Alcázar, Ángela; Carmona, Manuel; Borreguero, Ana M; de Lucas, Antonio; Rodríguez, Juan F

2015-01-01

Mercury is one of the most toxic pollutants, with high capacity of accumulation in living organism, causing important human health problems. Therefore, the mercury removal from water is an important research goal. In a previous work, an extractant agent [di(2-ethylhexyl)phosphoric acid] was microencapsulated in poly(styrene-co-divinylbenzene) by means of suspension polymerisation using toluene as diluent. In this study, this recipe has been modified changing the toluene by heptane and extended to four additional extractants (trioctylamine, trioctylmethylammonium chloride [TOMAC], tributyl phosphate and trioctylphosphine oxide). The polluting potential of the waste liquid from the process was measured by total organic carbon and chemical oxygen demand analyses. The morphology, particle size and distribution were studied by scanning electron microscopy and low angle laser light scattering. The amount of extractant agent into the microcapsules and the microencapsulation efficiency were determined by thermogravimetric analysis and the mercury removal capacity by equilibrium studies. Microcapsules containing TOMAC demonstrated to be the best material for the mercury removal and retention.

Quality of Life and Toxicity From Passively Scattered and Spot-Scanning Proton Beam Therapy for Localized Prostate Cancer

International Nuclear Information System (INIS)

Pugh, Thomas J.; Munsell, Mark F.; Choi, Seungtaek; Nguyen, Quyhn Nhu; Mathai, Benson; Zhu, X. Ron; Sahoo, Narayan; Gillin, Michael; Johnson, Jennifer L.; Amos, Richard A.; Dong, Lei; Mahmood, Usama; Kuban, Deborah A.; Frank, Steven J.; Hoffman, Karen E.; McGuire, Sean E.; Lee, Andrew K.

2013-01-01

Purpose: To report quality of life (QOL)/toxicity in men treated with proton beam therapy for localized prostate cancer and to compare outcomes between passively scattered proton therapy (PSPT) and spot-scanning proton therapy (SSPT). Methods and Materials: Men with localized prostate cancer enrolled on a prospective QOL protocol with a minimum of 2 years' follow-up were reviewed. Comparative groups were defined by technique (PSPT vs SSPT). Patients completed Expanded Prostate Cancer Index Composite questionnaires at baseline and every 3-6 months after proton beam therapy. Clinically meaningful differences in QOL were defined as ≥0.5 × baseline standard deviation. The cumulative incidence of modified Radiation Therapy Oncology Group grade ≥2 gastrointestinal (GI) or genitourinary (GU) toxicity and argon plasma coagulation were determined by the Kaplan-Meier method. Results: A total of 226 men received PSPT, and 65 received SSPT. Both PSPT and SSPT resulted in statistically significant changes in sexual, urinary, and bowel Expanded Prostate Cancer Index Composite summary scores. Only bowel summary, function, and bother resulted in clinically meaningful decrements beyond treatment completion. The decrement in bowel QOL persisted through 24-month follow-up. Cumulative grade ≥2 GU and GI toxicity at 24 months were 13.4% and 9.6%, respectively. There was 1 grade 3 GI toxicity (PSPT group) and no other grade ≥3 GI or GU toxicity. Argon plasma coagulation application was infrequent (PSPT 4.4% vs SSPT 1.5%; P=.21). No statistically significant differences were appreciated between PSPT and SSPT regarding toxicity or QOL. Conclusion: Both PSPT and SSPT confer low rates of grade ≥2 GI or GU toxicity, with preservation of meaningful sexual and urinary QOL at 24 months. A modest, yet clinically meaningful, decrement in bowel QOL was seen throughout follow-up. No toxicity or QOL differences between PSPT and SSPT were identified. Long-term comparative results in a

Intelligent Agent Appropriation in the Tracking Phase of an Environmental Scanning Process: A Case Study of a French Trade Union

Science.gov (United States)

Lafaye, Christophe

2009-01-01

Introduction: The rapid growth of the Internet has modified the boundaries of information acquisition (tracking) in environmental scanning. Despite the numerous advantages of this new medium, information overload is an enormous problem for Internet scanners. In order to help them, intelligent agents (i.e., autonomous, automated software agents…

Medical countermeasure against respiratory toxicity and acute lung injury following inhalation exposure to chemical warfare nerve agent VX

International Nuclear Information System (INIS)

Nambiar, Madhusoodana P.; Gordon, Richard K.; Rezk, Peter E.; Katos, Alexander M.; Wajda, Nikolai A.; Moran, Theodore S.; Steele, Keith E.; Doctor, Bhupendra P.; Sciuto, Alfred M.

2007-01-01

To develop therapeutics against lung injury and respiratory toxicity following nerve agent VX exposure, we evaluated the protective efficacy of a number of potential pulmonary therapeutics. Guinea pigs were exposed to 27.03 mg/m 3 of VX or saline using a microinstillation inhalation exposure technique for 4 min and then the toxicity was assessed. Exposure to this dose of VX resulted in a 24-h survival rate of 52%. There was a significant increase in bronchoalveolar lavage (BAL) protein, total cell number, and cell death. Surprisingly, direct pulmonary treatment with surfactant, liquivent, N-acetylcysteine, dexamethasone, or anti-sense syk oligonucleotides 2 min post-exposure did not significantly increase the survival rate of VX-exposed guinea pigs. Further blocking the nostrils, airway, and bronchioles, VX-induced viscous mucous secretions were exacerbated by these aerosolized treatments. To overcome these events, we developed a strategy to protect the animals by treatment with atropine. Atropine inhibits muscarinic stimulation and markedly reduces the copious airway secretion following nerve agent exposure. Indeed, post-exposure treatment with atropine methyl bromide, which does not cross the blood-brain barrier, resulted in 100% survival of VX-exposed animals. Bronchoalveolar lavage from VX-exposed and atropine-treated animals exhibited lower protein levels, cell number, and cell death compared to VX-exposed controls, indicating less lung injury. When pulmonary therapeutics were combined with atropine, significant protection to VX-exposure was observed. These results indicate that combinations of pulmonary therapeutics with atropine or drugs that inhibit mucous secretion are important for the treatment of respiratory toxicity and lung injury following VX exposure

Resistance to organophosphorus agent toxicity in transgenic mice expressing the G117H mutant of human butyrylcholinesterase

International Nuclear Information System (INIS)

Wang Yuxia; Ticu Boeck, Andreea; Duysen, Ellen G.; Van Keuren, Margaret; Saunders, Thomas L.; Lockridge, Oksana

2004-01-01

Organophosphorus toxicants (OP) include chemical nerve agents and pesticides. The goal of this work was to find out whether an animal could be made resistant to OP toxicity by genetic engineering. The human butyrylcholinesterase (BChE) mutant G117H was chosen for study because it has the unusual ability to hydrolyze OP as well as acetylcholine, and it is resistant to inhibition by OP. Human G117H BChE, under the control of the ROSA26 promoter, was expressed in all tissues of transgenic mice. A stable transgenic mouse line expressed 0.5 μg/ml of human G117H BChE in plasma as well as 2 μg/ml of wild-type mouse BChE. Intestine, kidneys, stomach, lungs, heart, spleen, liver, brain, and muscle expressed 0.6-0.15 μg/g of G117H BChE. Transgenic mice were normal in behavior and fertility. The LD50 dose of echothiophate for wild-type mice was 0.1 mg/kg sc. This dose caused severe cholinergic signs of toxicity and lethality in wild-type mice, but caused no deaths and only mild toxicity in transgenic animals. The mechanism of protection was investigated by measuring acetylcholinesterase (AChE) and BChE activity. It was found that AChE and endogenous BChE were inhibited to the same extent in echothiophate-treated wild type and transgenic mice. This led to the hypothesis that protection against echothiophate toxicity was not explained by hydrolysis of echothiophate. In conclusion, the transgenic G117H BChE mouse demonstrates the factors required to achieve protection from OP toxicity in a vertebrate animal

Crataegus monogyna fruit aqueous extract as a protective agent against doxorubicin-induced reproductive toxicity in male rats

Directory of Open Access Journals (Sweden)

Ali Shalizar Jalali

2013-04-01

Full Text Available Objective: Doxorubicin (DOX is a broad spectrum chemotherapeutic agent used in the treatment of several malignancies. The use of DOX in clinical chemotherapy has been restricted due to its diverse toxicities, including reproductive toxicity. Crataegus monogyna (C. monogyna is one of the oldest medicinal plants that have been shown to be cytoprotective because of scavenging free radicals. The present study was undertaken to determine whether C. monogyna fruits aqueous extract could serve as a protective agent against reproductive toxicity during DOX treatment in a rat model through antioxidant-mediated mechanisms. Materials and Methods: Male Wistar rats were allocated to four groups. Two groups of rats were treated with DOX at a dose of 4 mg/kg intraperitoneally on days 1, 7, 14, 21, and 28 (accumulated dose of 20 mg/kg. One of the groups received C. monogyna fruits aqueous extract at a dose of 20 mg/kg per day orally for 28 days along with DOX. A vehicle-treated control group and a C. monogyna control group were also included. Results: The DOX-treated group showed significant decreases in the body and organ weights and spermatogenic activities as well as many histological alterations. DOX treatment also caused a significant decrease in sperm count and motility with an increase in dead and abnormal sperms. Moreover, significant decrease in serum levels of testosterone and increased serum concentrations of FSH, LH, LDH, CPK, and SGOT were observed in DOX-treated rats. Notably, Crataegus co-administration caused a partial recovery in above-mentioned parameters. Conclusion: These findings indicated that doxorubicin can adversely damage the testicular tissue, while Crataegus co-administrationcould effectively prevent these adverse effects by effective inhibiting oxidative processes and restoration of antioxidant defense system.

Impact of gender on efficacy and acute toxicity of alkylating agent -based chemotherapy in Ewing sarcoma: secondary analysis of the Euro-Ewing99-R1 trial.

Science.gov (United States)

van den Berg, Henk; Paulussen, Michael; Le Teuff, Gwénaël; Judson, Ian; Gelderblom, Hans; Dirksen, Uta; Brennan, Bernadette; Whelan, Jeremy; Ladenstein, Ruth Lydia; Marec-Berard, Perrine; Kruseova, Jarmila; Hjorth, Lars; Kühne, Thomas; Brichard, Benedicte; Wheatley, Keith; Craft, Alan; Juergens, Heribert; Gaspar, Nathalie; Le Deley, Marie-Cécile

2015-11-01

Based on the randomised Euro-EWING99-R1 trial, vincristine, adriamycin, cyclophosphamide (VAC) may be able to replace vincristine, adriamycin, ifosfamide (VAI) in the treatment of standard-risk Ewing sarcoma. However some heterogeneity of treatment effect by gender was observed. The current exploratory study aimed at investigating the influence of gender on treatment efficacy and acute toxicity. Impact of gender on event-free survival (EFS), acute toxicity by course, switches between treatment arms and cumulative dose of alkylating agents was evaluated in multivariable models adjusted for age including terms to test for heterogeneity of treatment effect by gender. The analysis of the EFS was performed on the intention-to-treat population. EFS did not significantly differ between the 509 males and 347 females (p=0.33), but an interaction in terms of efficacy was suspected between treatment and gender (p=0.058): VAC was associated with poorer EFS than VAI in males, hazard ratio (HR) (VAC/VAI)=1.37 [95% confidence interval (CI), 0.98-1.90], contrasting with HR=0.81 [95%CI, 0.53-1.24] in females. Severe toxicity was more frequent in females, whatever the toxicity type. Thirty patients switched from VAI to VAC (9/251 males, 4%, and 21/174 females, 12%) mostly due to renal toxicity, and three from VAC to VAI (2/258 males, 0.8%, and 1/173 females, 0.6%). A reduction of alkylating agent cumulative dose >20% was more frequent in females (15% versus 9%, p=0.005), with no major difference between VAC and VAI (10% versus 13%, p=0.15). Differences of acute toxicity rate and cumulative doses of alkylating agents could not explain the marginal interaction observed in the Euro-EWING99-R1 trial data. Effects of gender-dependent polymorphism/activity of metabolic enzymes (e.g. known for CYP2B6) of ifosfamide versus cyclophosphamide should be explored. External data are required to further evaluate whether there is heterogeneity of alkylating agent effect by gender. NCT00987636 and

Protection against Radiotherapy-Induced Toxicity

Directory of Open Access Journals (Sweden)

Susan Hall

2016-07-01

Full Text Available Radiation therapy is a highly utilized therapy in the treatment of malignancies with up to 60% of cancer patients receiving radiation therapy as a part of their treatment regimen. Radiation therapy does, however, cause a wide range of adverse effects that can be severe and cause permanent damage to the patient. In an attempt to minimize these effects, a small number of compounds have been identified and are in use clinically for the prevention and treatment of radiation associated toxicities. Furthermore, there are a number of emerging therapies being developed for use as agents that protect against radiation-induced toxicities. The aim of this review was to evaluate and summarise the evidence that exists for both the known radioprotectant agents and the agents that show promise as future radioprotectant agents.

Chemical warfare agents. Classes and targets.

Science.gov (United States)

Schwenk, Michael

2018-09-01

Synthetic toxic chemicals (toxicants) and biological poisons (toxins) have been developed as chemical warfare agents in the last century. At the time of their initial consideration as chemical weapon, only restricted knowledge existed about their mechanisms of action. There exist two different types of acute toxic action: nonspecific cytotoxic mechanisms with multiple chemo-biological interactions versus specific mechanisms that tend to have just a single or a few target biomolecules. TRPV1- and TRPA-receptors are often involved as chemosensors that induce neurogenic inflammation. The present work briefly surveys classes and toxicologically relevant features of chemical warfare agents and describes mechanisms of toxic action. Copyright © 2017 Elsevier B.V. All rights reserved.

Nail toxicity induced by cancer chemotherapy.

Science.gov (United States)

Gilbar, Peter; Hain, Alice; Peereboom, Veta-Marie

2009-09-01

To provide a comprehensive literature review of chemotherapy-induced nail toxicity, including clinical presentation, implicated drugs and approaches for prevention and management. A search of MEDLINE and EMBASE (1966-2008) databases was conducted using the terms (and variations of the terms) antineoplastic agents, nails, nail toxicity, onycholysis, and paronychia. Bibliographies from selected articles were reviewed for appropriate references. The retrieved literature was reviewed to include all articles relevant to the clinical presentation, diagnosis, incidence, prevention, and treatment of chemotherapy-induced nail toxicity. Nail toxicity is a relatively uncommon adverse effect linked to a number of chemotherapeutic agents. Clinical presentation varies, depending on which nail structure is affected and the severity of the insult. Nail changes may involve all or some nails. Toxicity may be asymptomatic and limited to cosmetic concerns, however, more severe effects, involving pain and discomfort can occur. Taxanes and anthracyclines are the antineoplastic drug groups most commonly implicated. It is suggested that the administration schedule may influence the incidence of nail abnormalities, for example reported cases linked to the weekly administration of paclitaxel.Before instituting chemotherapy, patients should be educated regarding potential nail toxicities and strategies for prevention implemented. Management includes appropriate nail cutting, avoiding potential irritants, topical, or oral antimicrobials, and possibly cessation or dose reduction of the offending agent. Cryotherapy, through the application of frozen gloves or socks, has been beneficial in reducing docetaxel-induced nail toxicity and may be effective for other drugs.

Initial formal toxicity evaluation of APC-2, a novel fluorescent tracer agent for real-time measurement of glomerular filtration rate in preparation for a first-in-man clinical trial

Science.gov (United States)

Bugaj, Joseph E.; Dorshow, Richard B.

2014-03-01

The fluorescent tracer agent 2,5-bis[N-(1-carboxy-2-hydroxy)]carbamoyl-3,6-diaminopyrazine, designated APC-2, has been developed with properties and attributes necessary for use as a direct measure of glomerular filtration rate (GFR). Comparison to known standard exogenous GFR agents in animal models has demonstrated an excellent correlation. A clinical trial to demonstrate this same correlation in humans is in preparation. A battery of formal toxicity tests necessary for regulatory clearance to proceed with a clinical trial has been recently completed on this new fluorescent tracer agent. These include single dose toxicity studies in rats and dogs to determine overall toxicity and toxicokinetics of the compound. Blood compatibility, mutation assay, chromosomal aberration assay, and several other assays were also completed. Toxicity assessments were based on mortality, clinical signs, body weight, food consumption and anatomical pathology. Blood samples were collected to assess pharmacokinetic parameters including half-life, area under the curve, and clearance. Urine samples were collected to assess distribution. Doses of up to 200-300 times the estimated human dose were administered. No test-article related effects were noted on body weight, food consumption, ophthalmic observations and no abnormal pathology was seen in either macroscopic or microscopic evaluations of any organs or tissues. All animals survived to scheduled sacrifice. Transient discoloration of skin and urine was noted at the higher dose levels in both species as expected from a highly fluorescent compound and was not considered pathological. Thus initial toxicology studies of this new fluorescent tracer agent APC-2 have resulted in no demonstrable pathological test article concerns.

Bone scanning in the evaluation of lung cancer

International Nuclear Information System (INIS)

Jung, Kun Sik; Zeon, Seok Kil; Lee, Hee Jung; Song, Hong Suk

1994-01-01

We studied the diagnostic significance of bone scan in evaluation of bone metastasis by lung cancer, prevalence rate, and the causes of false positive bone scan and soft tissue accumulation of bone seeking agent. This subject include 73 lung cancer patients with bone scan, We analyzed the frequency of the metastasis, its distribution and configuration, and any relationship between bone pain and corresponding region on bone scan. The positive findings of bone scans were compared with simple X-ray film, CT, MRI and other diagnostic modalities. The false positive bone scan and the soft tissue accumulation of bone seeking agent were analyzed. The positive findings on bone scan were noted in 26 cases(36%) and they were coexistent with bone pain in 30%. The correspondence between bone scan and bone X-ray was 38%. False positive bone scans were seen in 12 cases(16%), which include fracture due to thoracotomy and trauma, degenerative bone disease, and bifid rib. Accumulation of bone seeking agent in soft tissue were seen in 13 cases(18%), which included primary tumor, enlarged cervical lymph node, pleural effusion, ascites and pleural thickening. Bone scans should be carefully interpreted in detecting bone metastasis in primary malignancy, because of the 16% false positivity and 18% soft tissue accumulation rate. It is very important to note that the correlation between bone pain and positive findings of bone scans was only 38%

Bone scanning in the evaluation of lung cancer

Energy Technology Data Exchange (ETDEWEB)

Jung, Kun Sik; Zeon, Seok Kil; Lee, Hee Jung; Song, Hong Suk [School of Medicine, Keimyung University, Daegu (Korea, Republic of)

1994-05-15

We studied the diagnostic significance of bone scan in evaluation of bone metastasis by lung cancer, prevalence rate, and the causes of false positive bone scan and soft tissue accumulation of bone seeking agent. This subject include 73 lung cancer patients with bone scan, We analyzed the frequency of the metastasis, its distribution and configuration, and any relationship between bone pain and corresponding region on bone scan. The positive findings of bone scans were compared with simple X-ray film, CT, MRI and other diagnostic modalities. The false positive bone scan and the soft tissue accumulation of bone seeking agent were analyzed. The positive findings on bone scan were noted in 26 cases(36%) and they were coexistent with bone pain in 30%. The correspondence between bone scan and bone X-ray was 38%. False positive bone scans were seen in 12 cases(16%), which include fracture due to thoracotomy and trauma, degenerative bone disease, and bifid rib. Accumulation of bone seeking agent in soft tissue were seen in 13 cases(18%), which included primary tumor, enlarged cervical lymph node, pleural effusion, ascites and pleural thickening. Bone scans should be carefully interpreted in detecting bone metastasis in primary malignancy, because of the 16% false positivity and 18% soft tissue accumulation rate. It is very important to note that the correlation between bone pain and positive findings of bone scans was only 38%.

Stabilized alcohol solution of reducing salt formulations for use in preparing radioisotope labelled scanning agents: liver scanning technetium-99m colloid and method of preparation

International Nuclear Information System (INIS)

1980-01-01

The preparation of a radiolabelled scanning agent for imaging reticuloendothelial organs, including the liver and spleen, is described. It consists of a sup(99m)Tc labelled colloid of a metal ion salt reductant, such as SnCl 2 , TiCl 3 , CrCl 2 or FeCl 2 , and an anhydrous non-oxidising organic solvent, such as diethyl ether, ethanol or another aliphatic alcohol. Examples are given of the effects of varying the pH, the metal ion salt reductant concentration, the eluate and solvent volumes and the temperature of the radiopharmaceutical on the tagging efficiency and organ distribution in mice and rabbits. (U.K.)

Gastrointestinal toxicity of vorinostat: reanalysis of phase 1 study results with emphasis on dose-volume effects of pelvic radiotherapy

LENUS (Irish Health Repository)

Bratland, Ase

2011-04-08

Abstract Background In early-phase studies with targeted therapeutics and radiotherapy, it may be difficult to decide whether an adverse event should be considered a dose-limiting toxicity (DLT) of the investigational systemic agent, as acute normal tissue toxicity is frequently encountered with radiation alone. We have reanalyzed the toxicity data from a recently conducted phase 1 study on vorinostat, a histone deacetylase inhibitor, in combination with pelvic palliative radiotherapy, with emphasis on the dose distribution within the irradiated bowel volume to the development of DLT. Findings Of 14 eligible patients, three individuals experienced Common Terminology Criteria of Adverse Events grade 3 gastrointestinal and related toxicities, representing a toxicity profile vorinostat has in common with radiotherapy to pelvic target volumes. For each study patient, the relative volumes of small bowel receiving radiation doses between 6 Gy and 30 Gy at 6-Gy intervals (V6-V30) were determined from the treatment-planning computed tomography scans. The single patient that experienced a DLT at the second highest dose level of vorinostat, which was determined as the maximum-tolerated dose, had V6-V30 dose-volume estimates that were considerably higher than any other study patient. This patient may have experienced an adverse radiation dose-volume effect rather than a toxic effect of the investigational drug. Conclusions When reporting early-phase trial results on the tolerability of a systemic targeted therapeutic used as potential radiosensitizing agent, radiation dose-volume effects should be quantified to enable full interpretation of the study toxicity profile. Trial registration ClinicalTrials.gov: NCT00455351

Gastrointestinal toxicity of vorinostat: reanalysis of phase 1 study results with emphasis on dose-volume effects of pelvic radiotherapy

International Nuclear Information System (INIS)

Bratland, Åse; Dueland, Svein; Hollywood, Donal; Flatmark, Kjersti; Ree, Anne H

2011-01-01

In early-phase studies with targeted therapeutics and radiotherapy, it may be difficult to decide whether an adverse event should be considered a dose-limiting toxicity (DLT) of the investigational systemic agent, as acute normal tissue toxicity is frequently encountered with radiation alone. We have reanalyzed the toxicity data from a recently conducted phase 1 study on vorinostat, a histone deacetylase inhibitor, in combination with pelvic palliative radiotherapy, with emphasis on the dose distribution within the irradiated bowel volume to the development of DLT. Of 14 eligible patients, three individuals experienced Common Terminology Criteria of Adverse Events grade 3 gastrointestinal and related toxicities, representing a toxicity profile vorinostat has in common with radiotherapy to pelvic target volumes. For each study patient, the relative volumes of small bowel receiving radiation doses between 6 Gy and 30 Gy at 6-Gy intervals (V6-V30) were determined from the treatment-planning computed tomography scans. The single patient that experienced a DLT at the second highest dose level of vorinostat, which was determined as the maximum-tolerated dose, had V6-V30 dose-volume estimates that were considerably higher than any other study patient. This patient may have experienced an adverse radiation dose-volume effect rather than a toxic effect of the investigational drug. When reporting early-phase trial results on the tolerability of a systemic targeted therapeutic used as potential radiosensitizing agent, radiation dose-volume effects should be quantified to enable full interpretation of the study toxicity profile.

General aspects of metal toxicity.

Science.gov (United States)

Kozlowski, H; Kolkowska, P; Watly, J; Krzywoszynska, K; Potocki, S

2014-01-01

This review is focused on the general mechanisms of metal toxicity in humans. The possible and mainly confirmed mechanisms of their action are discussed. The metals are divided into four groups due to their toxic effects. First group comprises of metal ions acting as Fenton reaction catalyst mainly iron and copper. These types of metal ions participate in generation of the reactive oxygen species. Metals such as nickel, cadmium and chromium are considered as carcinogenic agents. Aluminum, lead and tin are involved in neurotoxicity. The representative of the last group is mercury, which may be considered as a generally toxic metal. Fenton reaction is a naturally occurring process producing most active oxygen species, hydroxyl radical: Fe(2+) + He2O2 ↔ Fe(3+) + OH(-) + OH(•) It is able to oxidize most of the biomolecules including DNA, proteins, lipids etc. The effect of toxicity depends on the damage of molecules i.e. production site of the hydroxyl radical. Chromium toxicity depends critically on its oxidation state. The most hazardous seems to be Cr(6+) (chromates) which are one of the strongest inorganic carcinogenic agents. Cr(6+) species act also as oxidative agents damaging among other nucleic acids. Redox inactive Al(3+), Cd(2+) or Hg(2+) may interfere with biology of other metal ions e.g. by occupying metal binding sites in biomolecules. All these aspects will be discussed in the review.

Investigations of chemical warfare agents and toxic industrial compounds with proton-transfer-reaction mass spectrometry for a real-time threat monitoring scenario.

Science.gov (United States)

Kassebacher, Thomas; Sulzer, Philipp; Jürschik, Simone; Hartungen, Eugen; Jordan, Alfons; Edtbauer, Achim; Feil, Stefan; Hanel, Gernot; Jaksch, Stefan; Märk, Lukas; Mayhew, Chris A; Märk, Tilmann D

2013-01-30

Security and protection against terrorist attacks are major issues in modern society. One especially challenging task is the monitoring and protection of air conditioning and heating systems of buildings against terrorist attacks with toxic chemicals. As existing technologies have low selectivity, long response times or insufficient sensitivity, there is a need for a novel approach such as we present here. We have analyzed various chemical warfare agents (CWAs) and/or toxic industrial compounds (TICs) and related compounds, namely phosgene, diphosgene, chloroacetone, chloroacetophenone, diisopropylaminoethanol, and triethyl phosphate, utilizing a high-resolution proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOFMS) instrument with the objective of finding key product ions and their intensities, which will allow a low-resolution quadrupole mass spectrometry based PTR-MS system to be used with high confidence in the assignment of threat agents in the atmosphere. We obtained high accuracy PTR-TOFMS mass spectra of the six compounds under study at two different values for the reduced electric field in the drift tube (E/N). From these data we have compiled a table containing product ions, and isotopic and E/N ratios for highly selective threat compound detection with a compact and cost-effective quadrupole-based PTR-MS instrument. Furthermore, using chloroacetophenone (tear gas), we demonstrated that this instrument's response is highly linear in the concentration range of typical Acute Exposure Guideline Levels (AEGLs). On the basis of the presented results it is possible to develop a compact and cost-effective PTR-QMS instrument that monitors air supply systems and triggers an alarm as soon as the presence of a threat agent is detected. We hope that this real-time surveillance device will help to seriously improve safety and security in environments vulnerable to terrorist attacks with toxic chemicals. Copyright © 2012 John Wiley & Sons, Ltd.

Enhanced toxic cloud knockdown spray system for decontamination applications

Science.gov (United States)

Betty, Rita G [Rio Rancho, NM; Tucker, Mark D [Albuquerque, NM; Brockmann, John E [Albuquerque, NM; Lucero, Daniel A [Albuquerque, NM; Levin, Bruce L [Tijeras, NM; Leonard, Jonathan [Albuquerque, NM

2011-09-06

Methods and systems for knockdown and neutralization of toxic clouds of aerosolized chemical or biological warfare (CBW) agents and toxic industrial chemicals using a non-toxic, non-corrosive aqueous decontamination formulation.

CMCTS stabilized Fe3O4 particles with extremely low toxicity as highly efficient near-infrared photothermal agents for in vivo tumor ablation

Science.gov (United States)

Shen, Song; Kong, Fenfen; Guo, Xiaomeng; Wu, Lin; Shen, Haijun; Xie, Meng; Wang, Xinshi; Jin, Yi; Ge, Yanru

2013-08-01

With the potential uses of photothermal therapy (PTT) in cancer treatment with excellent efficacy, and the growing concerns about the nanotoxicity of hyperthermia agents such as carbon nanotubes and gold-based nanomaterials, the importance of searching for a biocompatible hyperthermia agent cannot be emphasized too much. In this work, a novel promising hyperthermia agent employing magnetic Fe3O4 particles with fairly low toxicity was proposed. This hyperthermia agent showed rapid heat generation under NIR irradiation. After modification with carboxymethyl chitosan (CMCTS), the obtained Fe3O4@CMCTS particles could disperse stably in PBS and serum without any aggregation. The modification of CMCTS could decrease the adsorption of bovine serum albumin (BSA) and improve the cellular uptake. In a comparative study with hollow gold nanospheres (HAuNS), Fe3O4@CMCTS particles exhibited a comparable photothermal effect and fairly low cytotoxicity. The in vivo magnetic resonance (MR) images of mice revealed that by attaching a magnet to the tumor, Fe3O4@CMCTS particles accumulated in the tumor after intravenous injection and showed a low distribution in the liver. After being exposed to a 808 nm laser for 5 min at a low power density of 1.5 W cm-2, the tumors on Fe3O4@CMCTS-injected mice reached a temperature of ~52 °C and were completely destroyed. Thus, a kind of multifunctional magnetic nanoparticle with extremely low toxicity and a simple structure for simultaneous MR imaging, targeted drug delivery and photothermal therapy can be easily fabricated.With the potential uses of photothermal therapy (PTT) in cancer treatment with excellent efficacy, and the growing concerns about the nanotoxicity of hyperthermia agents such as carbon nanotubes and gold-based nanomaterials, the importance of searching for a biocompatible hyperthermia agent cannot be emphasized too much. In this work, a novel promising hyperthermia agent employing magnetic Fe3O4 particles with fairly low

Assessment of myocardial perfusion using a new scanning agent

Energy Technology Data Exchange (ETDEWEB)

Khalil, M.N

1987-01-01

This work assessed a new compound: Tc-99m tertiary butyl isonitrile (T-BIN) in scanning the normal myocardium in dogs. Experimentally induced myocardial infarcts (M.I.) were detected. The compound cleared significantly from the blood within 15 minutes and from the lungs within an hour after intravenous administration. Liver uptake was high and remained so. Cardiac uptake occurred quickly and continued for 6 hours. Comparable results were obtained in normal humans and patients. Myocardial scanning was best after 60 minutes at rest or 30 minutes after exercise. Liver uptake sometimes obscured the detection of inferior M.I. but this problem was reduced using a 45/sup 0/ left anterior oblique view with a 20/sup 0/ cranial tilt. At rest 9/10 patients with M.I. showed defects corresponding to the infarct sites. In 20 patients with angina pectoris 16 had perfusion defects on exercise. In 15/16 patients reversible ischaemia was demonstrated. The reperfusion scans were best obtained at 4 hours post exercise. Both Tl-201 and T-BIN detected equally the infarcts (3/3) but in patients with angina 8/10 with T-BIN and 6/10 with Tl-201 showed defects. ECG gating of the T-BIN scans was also studied.

Gastrointestinal Toxicities With Combined Antiangiogenic and Stereotactic Body Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Pollom, Erqi L.; Deng, Lei [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Pai, Reetesh K. [Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States); Brown, J. Martin; Giaccia, Amato; Loo, Billy W.; Shultz, David B.; Le, Quynh Thu; Koong, Albert C. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Chang, Daniel T., E-mail: dtchang@stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States)

2015-07-01

Combining the latest targeted biologic agents with the most advanced radiation technologies has been an exciting development in the treatment of cancer patients. Stereotactic body radiation therapy (SBRT) is an ablative radiation approach that has become established for the treatment of a variety of malignancies, and it has been increasingly used in combination with biologic agents, including those targeting angiogenesis-specific pathways. Multiple reports have emerged describing unanticipated toxicities arising from the combination of SBRT and angiogenesis-targeting agents, particularly of late luminal gastrointestinal toxicities. In this review, we summarize the literature describing these toxicities, explore the biological mechanism of action of toxicity with the combined use of antiangiogenic therapies, and discuss areas of future research, so that this combination of treatment modalities can continue to be used in broader clinical contexts.

Studies on the toxicity of RSU-1069

International Nuclear Information System (INIS)

Whitmore, G.F.; Gulyas, S.

1986-01-01

RSU-1069 combines an aziridine function with a 2-nitroimidazole and has been reported to exhibit extraordinary radiosensitization both in vitro and in vivo. Such sensitization appears to be at variance with the electron affinity of the compound. In addition, recent experiments suggest that the compound is highly toxic to hypoxic tumor cells in vivo. On the assumption that the observed radiosensitizing ability may be a manifestation of toxicity and because of the high in vivo toxicity, we have investigated aerobic and hypoxic toxicity, both in wild type CHO cells and in mutants sensitive to a variety of DNA damaging agents. With wild type cells under aerobic conditions, the compound is approximately 50 times as toxic as misonidazole and under hypoxic conditions, approximately 250 times as toxic. The ratio of hypoxic to aerobic toxicity is approximately 80 times. Under aerobic conditions, repair-deficient mutants are 10 times as sensitive to RSU-1069 as wild type cells and approximately 100 times as sensitive under hypoxic conditions. The ratio of hypoxic to aerobic toxicity for the mutant cells is approximately 900. Based on these observations, we suggest that under aerobic conditions the aziridine function is primarily responsible for toxicity, whereas, under hypoxic conditions, the aziridine moiety combined with a reduced 2-nitroimidazole moiety produces a bifunctional agent

Modeling U-Shaped Exposure-Response Relationships for Agents that Demonstrate Toxicity Due to Both Excess and Deficiency.

Science.gov (United States)

Milton, Brittany; Farrell, Patrick J; Birkett, Nicholas; Krewski, Daniel

2017-02-01

Essential elements such as copper and manganese may demonstrate U-shaped exposure-response relationships due to toxic responses occurring as a result of both excess and deficiency. Previous work on a copper toxicity database employed CatReg, a software program for categorical regression developed by the U.S. Environmental Protection Agency, to model copper excess and deficiency exposure-response relationships separately. This analysis involved the use of a severity scoring system to place diverse toxic responses on a common severity scale, thereby allowing their inclusion in the same CatReg model. In this article, we present methods for simultaneously fitting excess and deficiency data in the form of a single U-shaped exposure-response curve, the minimum of which occurs at the exposure level that minimizes the probability of an adverse outcome due to either excess or deficiency (or both). We also present a closed-form expression for the point at which the exposure-response curves for excess and deficiency cross, corresponding to the exposure level at which the risk of an adverse outcome due to excess is equal to that for deficiency. The application of these methods is illustrated using the same copper toxicity database noted above. The use of these methods permits the analysis of all available exposure-response data from multiple studies expressing multiple endpoints due to both excess and deficiency. The exposure level corresponding to the minimum of this U-shaped curve, and the confidence limits around this exposure level, may be useful in establishing an acceptable range of exposures that minimize the overall risk associated with the agent of interest. © 2016 Society for Risk Analysis.

Role of {sup 18}F-FDG PET-CT in monitoring the cyclophosphamide induced pulmonary toxicity in patients with breast cancer - 2 Case Reports

Energy Technology Data Exchange (ETDEWEB)

Taywade, Sameer Kamalakar; Kumar, Rakesh; Bhethanabhotla, Sainath; Bal, Chandrasekhar [A.I.I.M.S, New Delhi (India)

2016-09-15

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 {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) uptake in lungs on fluorodeoxyglucose positron emission tomography-computed tomography ({sup 18}F-FDG PET-CT) has been elicited in literature in relation to lymphoma. However, limited data is available regarding the role of {sup 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 {sup 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 {sup 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.

Steroid hormones and brain development: some guidelines for understanding actions of pseudohormones and other toxic agents

Energy Technology Data Exchange (ETDEWEB)

McEwen, B.S.

1987-10-01

Gonadal, adrenal, and thyroid hormones affect the brain directly, and the sensitivity to hormones begins in embryonic life with the appearance of hormone receptor sites in discrete populations of neurons. Because the secretion of hormones is also under control by its neural and pituitary targets, the brain-endocrine axis during development is in a delicately balanced state that can be upset in various ways, and any agent that disrupts normal hormone secretion can upset normal brain development. Moreover, exogenous substances that mimic the actions of natural hormones can also play havoc with CNS development and differentiation. This paper addresses these issues in the following order: First, actions of glucocorticoids on the developing nervous system related to cell division dendritic growth and neurotransmitter phenotype will be presented followed by a discussion of the developmental effects of synthetic steroids. Second, actions of estrogens related to brain sexual differentiation will be described, followed by a discussion of the actions of the nonsteroidal estrogen, diethylstilbestrol, as an example of exogenous estrogenic substances. The most important aspect of the potency of exogenous estrogens appears to be the degree to which they either bypass protective mechanisms or are subject to transformations to more active metabolites. Third, agents that influence hormone levels or otherwise modify the neuroendocrine system, such as nicotine, barbiturates, alcohol, opiates, and tetrahydrocannabinol, will be noted briefly to demonstrate the diversity of toxic agents that can influence neural development and affect personality, cognitive ability, and other aspects of behavior. 53 references.

Toxic and carcinogenic agents in dry and moist snuff.

Science.gov (United States)

Hoffmann, D; Adams, J D; Lisk, D; Fisenne, I; Brunnemann, K D

1987-12-01

The oral use of snuff is causatively associated with cancer of the oral cavity. Since most epidemiologic studies to date relate to the long-term use of dry snuff, which has dominated the U.S. smokeless tobacco market in the past, the concentrations of several toxic and carcinogenic agents in the three most popular dry snuff brands have been compared with those in the five most popular moist snuff brands sold in the United States. All eight samples were analyzed for nitrate, alkaloids, polyphenols, volatile carbonyl compounds, lead, cadmium, selenium, and the carcinogenic compounds benzo[a]pyrene (CAS: 50-32-8), polonium-210 (CAS: 13981-52-7), volatile N-nitrosamines (VNAs), N-nitrosodiethanolamine (CAS: 1116-54-7), and the tobacco-specific N-nitrosamines (TSNAs). Most of the snuff brands were rich in nitrate (greater than or equal to 1.5%), total polyphenols (greater than 2%), and in nicotine (greater than or equal to 1.5%), which is the habituating factor in tobacco use. Concentrations of the VNAs were significantly above the permissible limits set for some food products; the concentrations of the TSNAs in both snuff types exceeded the levels of nitrosamines in other consumer products by at least two to three orders of magnitude. The extremely high levels of the TSNAs in snuff have remained unchanged during the last decade and present the major carcinogenic risk factor for the oral use of snuff. Polonium-210 contributes further to the carcinogenic risk associated with snuff. The chemical-analytical data presented in this study do not indicate marked differences in the carcinogenic potential of moist snuff compared to dry snuff.

Evaluation of antimicrobial activity of glycerol monolaurate nanocapsules against American foulbrood disease agent and toxicity on bees.

Science.gov (United States)

Lopes, Leonardo Q S; Santos, Cayane G; de Almeida Vaucher, Rodrigo; Gende, Liesel; Raffin, Renata P; Santos, Roberto C V

2016-08-01

The American Foulbrood Disease (AFB) is a fatal larval bee infection. The etiologic agent is the bacterium Paenibacillus larvae. The treatment involves incineration of all contaminated materials, leading to high losses. The Glycerol Monolaurate (GML) is a known antimicrobial potential compound, however its use is reduced due to its low solubility in water and high melting point. The nanoencapsulation of some drugs offers several advantages like improved stability and solubility in water. The present study aimed to evaluate the antimicrobial activity against P. larvae and the toxicity in bees of GML nanoparticles. The nanocapsules were produced and presented mean diameter of 210 nm, polydispersity index of 0.044, and zeta potential of -23.4 mV demonstrating the acceptable values to predict a stable system. The microdilution assay showed that it is necessary 142 and 285 μg/mL of GML nanocapsules to obtain a bacteriostatic and bactericidal effect respectively. The time-kill curve showed the controlled release of compound, exterminating the microorganism after 24 h. The GML nanocapsules were able to kill the spore form of Paenibacillus larvae while the GML do not cause any effect. The assay in bees showed that the GML has a high toxicity while the GML nanoparticles showed a decrease on toxic effects. Concluding, the formulation shows positive results in the action to combat AFB besides not causing damage to bees. Copyright © 2016 Elsevier Ltd. All rights reserved.

Assessment of oral toxicity and safety of pentamethylchromanol (PMCol), a potential chemopreventative agent, in rats and dogs

International Nuclear Information System (INIS)

Lindeblad, Matthew; Kapetanovic, Izet M.; Kabirov, Kasim K.; Detrisac, Carol J.; Dinger, Nancy; Mankovskaya, Irina; Zakharov, Alexander; Lyubimov, Alexander V.

2010-01-01

lower levels is considered to be less likely to result in toxicity following 28 days of exposure. Sex-related differences were seen in rats. Male rats appeared to have greater sensitivity to nephrotoxicity, while female animals had a greater incidence of hepatoxicity and changes in hematological parameters evaluated, especially at a dose of 500 mg/kg/day, which correlated to the higher plasma drug levels in female rats. It appeared that dogs were generally more sensitive than rats to oral administration of PMCol. Further examination of the potential toxic effects of PMCol in longer term studies is required prior to understanding the full risks of PMCol administration as a chemopreventative agent.

Prophylaxis and Therapy Against Chemical Agents

Science.gov (United States)

2009-11-01

Hematopoietic Consequences F. Dorandeu 5) pH Dependent Toxicity of Sulphur Mustard In Vitro J. Mikler Nerve Agents / Scavengers 1) Mutagenesis...symptoms such as salivation or shortness of breath and lower level exposures could be rendered inconsequential. B.2 CURRENT THERAPY FOR NERVE AGENT

Toxicity and sublethal effects of six insecticides to last instar larvae and adults of the biocontrol agents Chrysoperla carnea (Stephens) (Neuroptera: Chrysopidae) and Adalia bipunctata (L.) (Coleoptera: Coccinellidae).

Science.gov (United States)

Garzón, A; Medina, P; Amor, F; Viñuela, E; Budia, F

2015-08-01

To further develop Integrated Pest Management (IPM) strategies against crop pests, it is important to evaluate the effects of insecticides on biological control agents. Therefore, we tested the toxicity and sublethal effects (fecundity and fertility) of flonicamid, flubendiamide, metaflumizone, spirotetramat, sulfoxaflor and deltamethrin on the natural enemies Chrysoperla carnea and Adalia bipunctata. The side effects of the active ingredients of the insecticides were evaluated with residual contact tests for the larvae and adults of these predators in the laboratory. Flonicamid, flubendiamide, metaflumizone and spirotetramat were innocuous to last instar larvae and adults of C. carnea and A. bipunctata. Sulfoxaflor was slightly toxic to adults of C. carnea and was highly toxic to the L4 larvae of A. bipunctata. For A. bipunctata, sulfoxaflor and deltamethrin were the most damaging compounds with a cumulative larval mortality of 100%. Deltamethrin was also the most toxic compound to larvae and adults of C. carnea. In accordance with the results obtained, the compounds flonicamid, flubendiamide, metaflumizone and spirotetramat might be incorporated into IPM programs in combination with these natural enemies for the control of particular greenhouse pests. Nevertheless, the use of sulfoxaflor and deltamethrin in IPM strategies should be taken into consideration when releasing either of these biological control agents, due to the toxic behavior observed under laboratory conditions. The need for developing sustainable approaches to combine the use of these insecticides and natural enemies within an IPM framework is discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Assessment of Early Toxicity and Response in Patients Treated With Proton and Carbon Ion Therapy at the Heidelberg Ion Therapy Center Using the Raster Scanning Technique

Energy Technology Data Exchange (ETDEWEB)

Rieken, Stefan; Habermehl, Daniel; Nikoghosyan, Anna; Jensen, Alexandra [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Haberer, Thomas [Heidelberg Ion Therapy Center, Heidelberg (Germany); Jaekel, Oliver [Heidelberg Ion Therapy Center, Heidelberg (Germany); Department of Medical Physics, German Cancer Research Center (DKFZ), Heidelberg (Germany); Muenter, Marc W.; Welzel, Thomas; Debus, Juergen [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Combs, Stephanie E., E-mail: Stephanie.Combs@med.uni-hedielberg.de [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany)

2011-12-01

Puropose: To asses early toxicity and response in 118 patients treated with scanned ion beams to validate the safety of intensity-controlled raster scanning at the Heidelberg Ion Therapy Center. Patients and Methods: Between November 2009 and June 2010, we treated 118 patients with proton and carbon ion radiotherapy (RT) using active beam delivery. The main indications included skull base chordomas and chondrosarcomas, salivary gland tumors, and gliomas. We evaluated early toxicity within 6 weeks after RT and the initial clinical and radiologic response for quality assurance in our new facility. Results: In all 118 patients, few side effects were observed, in particular, no high numbers of severe acute toxicity were found. In general, the patients treated with particle therapy alone showed only a few single side effects, mainly Radiation Therapy Oncology Group/Common Terminology Criteria grade 1. The most frequent side effects and cumulative incidence of single side effects were observed in the head-and-neck patients treated with particle therapy as a boost and photon intensity-modulated RT. The toxicities included common radiation-attributed reactions known from photon RT, including mucositis, dysphagia, and skin erythema. The most predominant imaging responses were observed in patients with high-grade gliomas and those with salivary gland tumors. For skull base tumors, imaging showed a stable tumor outline in most patients. Thirteen patients showed improvement of pre-existing clinical symptoms. Conclusions: Side effects related to particle treatment were rare, and the overall tolerability of the treatment was shown. The initial response was promising. The data have confirmed the safe delivery of carbon ions and protons at the newly opened Heidelberg facility.

Effects of chelating agent CBMIDA on the toxicity of depleted uranium administered subcutaneously in rats

International Nuclear Information System (INIS)

Fukuda, Satoshi; Ikeda, Mizuyo; Nakamaura, Mariko

2008-01-01

We examined the acute toxicity of depleted uranium (DU) after subcutaneous injection as a simulated wounds model, and the effects of the chelating agent catechol-3,6-bis(methyliminodiacetic acid) (CBMIDA), by local treatment in rats. First, to examine the initial behavior and toxicity of uranium of different chemical forms, male Wistar rats were subcutaneously injected with 4 and 16 mg/kg DU (pH 1) in a solution of pH 1 and 7, respectively, and were killed 1, 3, 6 and 24 hours later. After the injection of DU(pH1), about 60% of the uranium was retained for first 1-3 hours at the injected sites, and then decreased to 16% at 24 hours in the 4 mg/kg DU group; however, the uranium did not change significantly in the 16 mg/kg DU group. Urinary excretion rates of uranium increased in a time-independent manner after the injection Depositions of uranium in the liver, kidneys and femur were found at 1 hour after DU injection, with significant increases in serum and urinary biochemical markers indicating acute and severe damage. The results of the DU (pH 7) injection were useful for estimating the toxicity of uranium by the chemical changes in the body. Second, CBMIDA (480 mg/kg) was infused into the DU-injected site at 0, 10, 30, 60 min and 24 hours after the subcutaneous injection of 4 mg/kg DU (pH 1 and 7). When CBMIDA was administered within 120 min after DU (pH 1) injection, the uranium at the injected sites decreased to 4-17% of that in the no-treatment DU (pH 1) group, and was excreted effectively in the urine and feces, with decreased levels in the kidneys and femur. The results indicated that the subcutaneously injected uranium acutely induced severe damage in the DU-injected sites and organs after DU intake, relating to chemical forms of uranium by pH and that local treatment of CBMIDA was effective in decreasing the acute toxicity of uranium if carried out as early as possible (at least within 2 hours) after DU administration. (author)

VARIATIONS IN REPRODUCTIVE TOXICANT IDENTIFICATION

Energy Technology Data Exchange (ETDEWEB)

Simmons, F

2008-05-13

Reproductive toxicants are a very important class of compounds. They present unique hazards to those of child bearing ages, perform their 'dirty work' using a wide variety of mechanisms on a number of different organs, and are regulatorily important. Because of all of this, properly identifying reproductive toxicants is important, but fraught with difficulty. In this paper we will describe types or reproductive toxicants, their importance, and both mistakes and good practices that people who are not experts in reproductive toxicology may use in their attempts to identify them. Additionally, this paper will focus on chemical reproductive toxicants and will not address biological agents that could affect reproductive toxicity although many principles outlined here could be applied to that endeavor.

Mitochondrial Toxicity in Human Pregnancy: An Update on Clinical and Experimental Approaches in the Last 10 Years

Directory of Open Access Journals (Sweden)

Constanza Morén

2014-09-01

Full Text Available Mitochondrial toxicity can be one of the most dreadful consequences of exposure to a wide range of external agents including pathogens, therapeutic agents, abuse drugs, toxic gases and other harmful chemical substances. However, little is known about the effects of mitochondrial toxicity on pregnant women exposed to these agents that may exert transplacental activity and condition fetal remodeling. It has been hypothesized that mitochondrial toxicity may be involved in some adverse obstetric outcomes. In the present study, we investigated the association between exposure to mitochondrial toxic agents and pathologic conditions ranging from fertility defects, detrimental fetal development and impaired newborn health due to intra-uterine exposure. We have reviewed data from studies in human subjects to propose mechanisms of mitochondrial toxicity that could be associated with the symptoms present in both exposed pregnant and fetal patients. Since some therapeutic interventions or accidental exposure cannot be avoided, further research is needed to gain insight into the molecular pathways leading to mitochondrial toxicity during pregnancy. The ultimate objective of these studies should be to reduce the mitochondrial toxicity of these agents and establish biomarkers for gestational monitoring of harmful effects.

Hyperthermia and chemotherapy agent

International Nuclear Information System (INIS)

Roizin-Towle, L.; Hall, E.J.

1981-01-01

The use of chemotherapeutic agents for the treatment of cancer dates back to the late 19th century, but the modern era of chemotherapy drugs was ushered in during the 1940's with the development of the polyfunctional alkylating agent. Since then, numerous classes of drugs have evolved and the combined use of antineoplastic agents with other treatment modalities such as radiation or heat, remains a large relatively unexplored area. This approach, combining local hyperthermia with chemotherapy agents affords a measure of targeting and selective toxicity not previously available for drugs. In this paper, the effects of adriamycin, bleomycin and cis-platinum are examined. The adjuvant use of heat may also reverse the resistance of hypoxic cells noted for some chemotherapy agents

Pulmonary drug toxicity. FDG-PET findings in patients with lymphoma

International Nuclear Information System (INIS)

Kazama, Toshiki; Faria, S.C.; Macapinlac, H.A.; Uchida, Yoshitaka; Ito, Hisao

2008-01-01

The objective of this study was to evaluate the prevalence and positron emission tomography (PET) imaging features of pulmonary drug toxicity in patients with lymphoma during or just following chemotherapy. A total of 677 PET scans on 460 patients with lymphoma (351 non-Hodgkin's lymphoma, 92 Hodgkin's disease, and 17 both Hodgkin's and non-Hodgkin's lymphoma) were performed for the evaluation of chemotherapy response. In 51 patients, abnormal accumulation on both sides of the chest was reported. A review of medical records, 18 fluorodeoxyglucose ( 18 FDG)-PET scans, and chest computed tomography (CT) was performed, and cases with probable drug toxicity were identified. Inclusion criteria of probable drug toxicity were abnormal but symmetrical FDG accumulation in both lungs seen during or just following the completion of chemotherapy, the abnormal accumulation or corresponding abnormal CT findings resolved on subsequent studies, exclusion of clinical diagnosis of pneumonia, radiation pneumonitis, or lymphoma involvement. In 10 patients (six men and four women, average age 47.3), 2.2% of cases, probable drug toxicity was identified. In all 10 cases, diffuse and subpleural-dominant FDG accumulation was seen on FDG-PET scans, and scattered or diffuse ground-glass opacities were observed on chest CT. Four patients reported symptoms, and six patients did not report any symptoms. Diffuse and peripheral-dominant FDG accumulation in the lung, which may represent pulmonary drug toxicity, was not uncommon in patients with lymphoma who underwent chemotherapy. FDG-PET scan might be able to detect pulmonary drug toxicity in asymptomatic patients. (author)

Toxicity evaluation of Gd2O3@SiO2 nanoparticles prepared by laser ablation in liquid as MRI contrast agents in vivo

Directory of Open Access Journals (Sweden)

Tian XM

2014-08-01

Full Text Available Xiumei Tian,1,* Fanwen Yang,1,* Chuan Yang,2 Ye Peng,1 Dihu Chen,3 Jixiang Zhu,1 Fupo He,1 Li Li,2 Xiaoming Chen11Department of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 2State Key Laboratory of Oncology in South China, Imaging Diagnosis and Interventional Center, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong Province, People’s Republic of China; 3State Key Laboratory of Optoelectronic Materials and Technologies, School of Physics and Engineering, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China*These authors contributed equally to this workAbstract: Poor toxicity characterization is one obstacle to the clinical deployment of Gd2O3@SiO2 core-shell nanoparticles (Gd-NPs for use as magnetic resonance (MR imaging contrast agents. To date, there is no systematic toxicity data available for Gd-NPs prepared by laser ablation in liquid. In this article, we systematically studied the Gd-NPs’ cytotoxicity, apoptosis in vitro, immunotoxicity, blood circulation half-life, biodistribution and excretion in vivo, as well as pharmacodynamics. The results show the toxicity, and in vivo MR data show that these NPs are a good contrast agent for preclinical applications. No significant differences were found in cell viability, apoptosis, and immunotoxicity between our Gd-NPs and Gd in a DTPA (diethylenetriaminepentaacetic acid chelator. Biodistribution data reveal a greater accumulation of the Gd-NPs in the liver, spleen, lung, and tumor than in the kidney, heart, and brain. Approximately 50% of the Gd is excreted via the hepatobiliary system within 4 weeks. Furthermore, dynamic contrast-enhanced T1-weighted MR images of xenografted murine tumors were obtained after intravenous administration of the Gd-NPs. Collectively, the single step preparation of Gd-NPs by laser ablation in liquid produces particles with satisfactory cytotoxicity

Body composition in chemotherapy: the promising role of CT scans.

Science.gov (United States)

Prado, Carla M M

2013-09-01

Reducing cancer-treatment toxicity was a largely ignored research agenda, which is now emerging as an active area of investigation. Studies of human body composition using computerized tomography scans have provided proof-of-concept that variability in drug disposition and toxicity profiles may be partially explained by different features in body composition. Collectively, studies suggest that skeletal muscle depletion (regardless of body weight) is an independent predictor of severe toxicity, affecting cancer treatment and its outcomes. Although precise mechanisms are unknown, pharmacokinetic parameters such as variations in volume of distribution and increased drug exposure may explain such findings. Computerized tomography scans are readily available in clinical databases of diagnostic images and provide feasible, reliable, and highly differentiated measurements of body composition. These images should be used to optimize screening and management of patients in order to prevent severe toxicity, and to improve the efficacy and cost-efficiency of chemotherapy treatments.

Local anaesthetic toxicity

African Journals Online (AJOL)

Local anaesthetic toxicity has been known since the introduction of local anaesthetic drugs into anaesthetic practice more than a hundred ... was the first to think of cocaine as a narcotic. ..... anaesthetics act as Na+ channel-blocking agents, they slow down .... all neurons, leading to global CNS depression, slowing and.

The effectiveness of processed grapefruit-seed extract as an antibacterial agent: II. Mechanism of action and in vitro toxicity.

Science.gov (United States)

Heggers, John P; Cottingham, John; Gusman, Jean; Reagor, Lee; McCoy, Lana; Carino, Edith; Cox, Robert; Zhao, Jian-Gang; Reagor, Lana

2002-06-01

Recent testimonials report grapefruit-seed extract, or GSE (Citricidal) to be effective against more than 800 bacterial and viral strains, 100 strains of fungus, and a large number of single and multicelled parasites. This study investigated GSE for antibacterial activity at varying time intervals and concentration levels and tissue toxicity at varying concentrations in an effort to determine if a concentration existed that was both microbicidal and nontoxic and in what period of time. Gram-negative and gram-positive isolates were introduced into graduated dilutions of GSE (twofold concentrations ranging from 1:1, through 1:512) for determination of bacterial activity. In vitro assays with human skin fibroblast cells were also performed at the same dilutions to determine toxicity. These tests indicated that from the 1:1 through the 1:128 concentrations, GSE remained toxic as well as bactericidal. However, test results indicated that at the 1:512 dilution, GSE remained bactericidal, but completely nontoxic. The initial data shows GSE to have antimicrobial properties against a wide range of gram-negative and gram-positive organisms at dilutions found to be safe. With the aid of scanning transmission electron microscopy (STEM), the mechanism of GSE's antibacterial activity was revealed. It was evident that GSE disrupts the bacterial membrane and liberates the cytoplasmic contents within 15 minutes after contact even at more dilute concentrations.

Progress in the development of short term chronic toxicity testing methods for crude oil and commercial bioremediation agents

International Nuclear Information System (INIS)

Cavender, R.C.; Cherry, D.S.; Dobbs, M.G.; Bidwell, J.R.; Yeager, M.M.

1995-01-01

Proposed modifications to the National Oil and Hazardous Substance Pollution Contingency Plan (NCP) have prompted examinations of the methodology used in toxicity testing of the water soluble fraction of oil, commercial bioremediation agents (CBA), and a combination of the two. The specific concerns addressed by this research are the use of unweathered Alaska North Slope (ANS) crude oil instead of the more expensive, less environmentally realistic distillate ANS-521, and the appropriate laboratory preparation methodology for the water soluble fraction (WSF) used in testing. Seven-day chronic tests exposing the inland silverside (Menidia beryllina) and estuarine mysid (Mysidopsis bahia) to the water soluble fraction of unweathered ANS and ANS-521 showed that mysids responded similarly to the two types of oils while silversides were more sensitive to unweathered ANS. In the presence of a CBA and WSF, the mortality of the organisms and the mysid growth were similar in both types of oil. The NOEC for silverside growth, however, was lower in the combined exposure of a CBA with ANS-521 WSF than it was in the CBA-WSF unweathered ANS. Testing is underway to determine if the stirring time length effects the toxicity of the WSF, or the WSF and CBA combination. In chronic tests using both the silverside and mysid there were no differences in growth and mortality of the organisms tested in WSF prepared from 10 and 20 hours of stirring, however, the 5 hour stirring exposure is less toxic to both organisms

A microneedle biosensor for minimally-invasive transdermal detection of nerve agents.

Science.gov (United States)

Mishra, Rupesh K; Vinu Mohan, A M; Soto, Fernando; Chrostowski, Robert; Wang, Joseph

2017-03-13

A microneedle electrochemical biosensor for the minimally invasive detection of organophosphate (OP) chemical agents is described. The new sensor relies on the coupling of the effective biocatalytic action of organophosphorus hydrolase (OPH) with a hollow-microneedle modified carbon-paste array electrode transducer, and involves rapid square-wave voltammetric (SWV) measurements of the p-nitrophenol product of the OPH enzymatic reaction in the presence of the OP substrate. The scanning-potential SWV transduction mode offers an additional dimension of selectivity compared to common fixed-potential OPH-amperometric biosensors. The microneedle device offers a highly linear response for methyl paraoxon (MPOx) over the range of 20-180 μM, high selectivity in the presence of excess co-existing ascorbic acid and uric acid and a high stability sensor upon exposure to the interstitial fluid (ISF). The OPH microneedle sensor was successfully tested ex vivo using mice skin samples exposed to MPOx, demonstrating its promise for minimally-invasive monitoring of OP agents and pesticides and as a wearable sensor for detecting toxic compounds, in general.

Curcumin mitigates fenthion-induced testicular toxicity in rats ...

African Journals Online (AJOL)

Fenthion is a widely used organophosphorus pesticide in agriculture that induces different cytotoxic effects, including male reproductive toxicity. The present work aimed to study the ameliorative effects of curcumin, a potential therapeutic agent against several chronic diseases, on reproductive toxicity induced by the ...

Evaluation of the diagnostic efficacy of autologous 111In-labelled platelets as a scanning agent for deep vein thrombosis in the chacma baboon

International Nuclear Information System (INIS)

Dormehl, I.C.; Du Plessis, M.; Jacobs, D.J.; Pretorius, J.P.; Franz, R.C.

1985-01-01

The diagnostic efficiency of autologous sup(111I)n-labelled platelets (ILP) as a scanning agent in deep veinthrombosis (DVT) was investigated in 24 South African baboons (Papio ursinus). Thrombi were surgically induced by stasis, intimal injury and the injection of thrombin in the common femoral veins of adult baboons. The thrombi were allowed to age for 1, 2, 4, 8, 24, 48 and 72 h before injecting the ILP. Scanning was done with a large field gamma camera at 10 min post injection and again at 2, 4, 6, 8, 10, 14, 24, 48 and 72 h. Time-activity curves were thus obtained and it was possible to establish an optimal time after injection of the ILP to scan for each group of thrombi. The results indicate that only the younger thrombi (1-8 h after thrombus formation) were detected. Twenty-four hour and older thrombi were not visualised. A favourable time to scan in the case of the younger thrombi appeared to be approximately 20 h after the injection of ILP. However, the thrombus age limitation still impairs the diagnostic efficiency of the procedure. (orig.)

Precursor and Neutral Loss Scans in an RF Scanning Linear Quadrupole Ion Trap

Science.gov (United States)

Snyder, Dalton T.; Szalwinski, Lucas J.; Schrader, Robert L.; Pirro, Valentina; Hilger, Ryan; Cooks, R. Graham

2018-03-01

Methodology for performing precursor and neutral loss scans in an RF scanning linear quadrupole ion trap is described and compared to the unconventional ac frequency scan technique. In the RF scanning variant, precursor ions are mass selectively excited by a fixed frequency resonance excitation signal at low Mathieu q while the RF amplitude is ramped linearly to pass ions through the point of excitation such that the excited ion's m/z varies linearly with time. Ironically, a nonlinear ac frequency scan is still required for ejection of the product ions since their frequencies vary nonlinearly with the linearly varying RF amplitude. In the case of the precursor scan, the ejection frequency must be scanned so that it is fixed on a product ion m/z throughout the RF scan, whereas in the neutral loss scan, it must be scanned to maintain a constant mass offset from the excited precursor ions. Both simultaneous and sequential permutation scans are possible; only the former are demonstrated here. The scans described are performed on a variety of samples using different ionization sources: protonated amphetamine ions generated by nanoelectrospray ionization (nESI), explosives ionized by low-temperature plasma (LTP), and chemical warfare agent simulants sampled from a surface and analyzed with swab touch spray (TS). We lastly conclude that the ac frequency scan variant of these MS/MS scans is preferred due to electronic simplicity. In an accompanying manuscript, we thus describe the implementation of orthogonal double resonance precursor and neutral loss scans on the Mini 12 using constant RF voltage. [Figure not available: see fulltext.

Development of Medical Technology for Contingency Response to Marrow Toxic Agents

Science.gov (United States)

2014-05-06

Specific Oligonucleotides SSP Sequence Specific Primers SSOP Sequence Specific Oligonucleotide Probes STAR ® Search, Tracking and Registry TBI Total... white paper detailing recommendations/guidelines for the assessment of new assays (potency or other assays) relevant to cord blood banking and/or...Irradiation - Marcel van den Brink (Memorial Sloan Kettering Cancer Center) 5. Organ Toxicity: h. Pulmonary Toxicity - Zeljko Vujaskovic (Duke) i

Toxicity of tritium

International Nuclear Information System (INIS)

Dobson, R.L.

1979-01-01

Among radionuclides of importance in atomic energy, 3 H has relatively low toxicity. The main health and environmental worry is the possibility that significant biological effects may follow from protracted exposure to low concentrations in water. To examine this possible hazard and measure toxicity at low tritium concentrations, chronic exposure studies were done on mice and monkeys. During vulnerable developmental periods animals were exposed to 3 HOH, and mice were exposed also to 60 Co gamma irradiation and energy-related chemical agents. The biological endpoint measured was the irreversible loss of female germ cells. Effects from tritium were observed at surprisingly low concentrations where 3 H was found more damaging than previously thought. Comparisons between tritium and gamma radiation showed the relative biological effectiveness (RBE) to be greater than 1 and to reach approximately 3 at very low exposures. For perspective, other comparisons were made: between radiation and chemical agents, which revealed parallels in action on germ cells, and between pre- and postnatal exposure, which warn of possible special hazard to the fetus from both classes of energy-related byproducts

Fire Extinguishing Agents for Protection of Occupied Spaces in Military Ground Vehicles

Science.gov (United States)

2015-10-14

unlimited. 10 Comparison of Fluorinated Agents UNCLASSIFIED: Distribution Statement A. Approved for public release; distribution is unlimited. 11... Toxicity evaluation of candidate agents – Long-term storage and material compatibility of agent mixtures and storage containers – Agent distribution

Gadolinium based contrast agents in current practice: Risks of accumulation and toxicity in patients with normal renal function

Directory of Open Access Journals (Sweden)

Anju Ranga

2017-01-01

Full Text Available Despite being decked as the most prized compounds in the nugget box of contrast agents for clinical radiologists, and carrying an indisputable tag of safety of the US Food and Drug Administration for close to three decades, all may not be seemingly well with the family of gadolinium compounds. If the first signs of violations of primum non nocere in relation to gadolinium-based contrast agents (GBCAs appeared in the millennium year with the first published report of skin fibrosis in patients with compromised renal function, the causal relationship between the development of nephrogenic systemic fibrosis (NSF and GBCAs, first proposed by two European groups in 2006, further precluded their use in renocompromised patients. The toxicity, pharmacokinetics, and pharmacodynamics of GBCAs, however, has come under hawk-eyed scrutiny with recent reports that gadolinium tends to deposit cumulatively in the brain of patients with normal hepatobiliary function and intact blood–brain barrier. While the jury on the long-term hazard significance of this critical scientific finding is still out, the use of GBCAs must be guided by due clinical diligence, avoidance of repeated doses, and preferring GBCAs with the best safety profiles.

Research on environmental impact of water-based fire extinguishing agents

Science.gov (United States)

Wang, Shuai

2018-02-01

This paper offers current status of application of water-based fire extinguishing agents, the environmental and research considerations of the need for the study of toxicity research. This paper also offers systematic review of test methods of toxicity and environmental impact of water-based fire extinguishing agents currently available, illustrate the main requirements and relevant test methods, and offer some research findings for future research considerations. The paper also offers limitations of current study.

The diagnostic value of monoclonal antibody scan (leucoscan) compared with 99mTc MDP bone scan and Ga 67 in diagnosing bone and joint infection

International Nuclear Information System (INIS)

Koukouraki, S.I.; Velidaki, A.; Prassopoulos, V.; Karkavitsas, N.; Vavouranakis, H.; Hatjipavlou, A.

2002-01-01

Full text: Nowadays different radiopharmaceuticals have been developed as 99mTc MDP, 67Ga citrate, 111In oxine- and 99mTc HMPAO labeled leucocytes for the accurate localization of bone/joint infection, but all of them have limitations that encouraged the search of new agents characterized from high and early uptake in infectious/inflammatory tissues, low toxicity and no accumulation in non inflamed tissues. The purpose of this study is to compare the diagnostic value of a 99mTc labeled antigranulocyte Fab' fragment (Leucoscan) with 99mTc MDP bone scan and 67 Ga. The monoclonal antibody, Leucoscan, is an IgG murine Fab' fragment directed against a NCA-90 epitope located on the surface of granulocytes. 45 patients with suspected bone and joint infection (18 total hip prosthesis, 4 knee prosthesis, 8 vertebral infection and 15 long bones) were included in this study. All patients underwent conventional Rx, bone scan, 67Ga scan and Leucoscan. Three phase 99mTc MDP bone scan and 67Ga scan were performed using standard procedures. For Leucoscan the antibody was labeled with 25 mCi of 99mTc and was infected intravenously over 30 seconds. Ten minutes planar images were taken 1 h and 2 hrs p.i using a GE Millennium γ camera provided with a LEGP collimator. Images were evaluated as score 1 (no abnormal uptake), score 2 (probably positive), score 3 (definitely infected) according the intensity of abnormally increased uptake. Results were compared with 99mTc MDP bone scan and 67Ga scans. The final diagnosis was given by the surgical verification with histopathology or culture. All 45 patients had pathologic proof of presence/absence of bone and joint infection. 36/45 were positive for bone or joint infection and 9/45 were negative.30/36 patients with surgically proven bone and joint infection had true positive Leucoscan, 26/36 had true positive MDP bone scan and 20/36 true positive 67Ga scan. Nine out of 9 patients with proven absence of inflammation had true negative

Borocaptate sodium (BSH) toxicity issues

International Nuclear Information System (INIS)

LaHann, T.

1995-01-01

ISU's Center for Toxicology Research has been conducting toxicity testing of borocaptate sodium (BSH) to aid in assessing if proposed human studies of BSH are likely to be acceptably safe. This report describes BSH interactions with other biological agents

Probing cytotoxicity of nanoparticles and organic compounds using scanning proton microscopy, scanning electron microscopy and fluorescence microscopy

Energy Technology Data Exchange (ETDEWEB)

Tong Yongpeng [Institute of Nuclear Techniques, Shenzhen University, Nanhai Avenue 3688, Shenzhen 518060 (China)], E-mail: yongpengt@yahoo.com.cn; Li Changming [School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637457 (Singapore); Liang Feng [Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025 (China); Chen Jianmin [Shenzhen Municipal Hospital for Chronic Disease Control and Prevention, Guangdong 518020 (China); Zhang Hong; Liu Guoqing; Sun Huibin [Institute of Nuclear Techniques, Shenzhen University, Nanhai Avenue 3688, Shenzhen 518060 (China); Luong, John H.T. [Biotechnology Research Institute, National Research Council Canada, Montreal, Quebec, H4P 2R2 (Canada)

2008-12-15

Scanning proton microscopy, scanning electron microscopy (SEM) and fluorescence microscopy have been used to probe the cytotoxicity effect of benzo[a]pyrene (BaP), ethidium bromide (EB) and nanoparticles (ZnO, Al{sub 2}O{sub 3} and TiO{sub 2}) on a T lymphoblastic leukemia Jurkat cell line. The increased calcium ion (from CaCl{sub 2}) in the culture medium stimulated the accumulation of BaP and EB inside the cell, leading to cell death. ZnO, Al{sub 2}O{sub 3} and TiO{sub 2} nanoparticles, however, showed a protective effect against these two organic compounds. Such inorganic nanoparticles complexed with BaP or EB which became less toxic to the cell. Fe{sub 2}O{sub 3} nanoparticles as an insoluble particle model scavenged by macrophage were investigated in rats. They were scavenged out of the lung tissue about 48 h after infection. This result suggest that some insoluble inorganic nanoparticles of PM (particulate matters) showed protective effects on organic toxins induced acute toxic effects as they can be scavenged by macrophage cells. Whereas, some inorganic ions such as calcium ion in PM may help environmental organic toxins to penetrate cell membrane and induce higher toxic effect.

New Histologic Findings in Idiopathic Mesenteric Phlebosclerosis: Clues to Its Pathogenesis and Etiology—Probably Ingested Toxic Agent-related

Directory of Open Access Journals (Sweden)

Kuo-Ming Chang

2007-06-01

Conclusion: A pathogenesis is suggested for at least a subgroup of cases of IMP: the disease is initiated by a slow but longstanding direct hypoxic injury to the venous muscular layer, which leads to gradual mummification and then sclerosis and calcification of the venous muscle. This is followed by the repeated same damage of the subsequent reactively hyper-plastic myointima in the veins, and these changes finally result in gradual venous occlusion. Certain toxins or biochemi-cals, probably existing in the frequently ingested contents and absorbed to the venous return, may play the most important role in this damage. However, analysis of more cases is required to support the proposal, and if such support is found, the toxic agents remain to be clarified via further laboratory investigations.

Biodistribution, toxicity and radiation dosimetry studies of the serotonin transporter radioligand 4-[{sup 18}F]-ADAM in rats and monkeys

Energy Technology Data Exchange (ETDEWEB)

Huang, Ya-Yao [Tri-Service General Hospital, PET Center, Department of Nuclear Medicine, Taipei (China); National Tsing Hua University, Department of Biomedical Engineering and Environmental Sciences, Hsinchu (China); Ma, Kuo-Hsing [National Defense Medical Center, Department of Biology and Anatomy, Taipei (China); Tseng, Ta-Wei; Chou, Ta-Kai; Huang, Wen-Sheng [Tri-Service General Hospital, PET Center, Department of Nuclear Medicine, Taipei (China); Ng, Hanna; Mirsalis, Jon C. [SRI International, Menlo Park, CA (United States); Fu, Ying-Kai [Institute of Nuclear Energy Research, Taoyuan (China); Chung Yuan Christian University, Department of Chemistry, Chung-Li (China); Chu, Tieh-Chi [National Tsing Hua University, Department of Biomedical Engineering and Environmental Sciences, Hsinchu (China); Yuanpei University, Department of Radiological Technology, Hsinchu (China); Shiue, Chyng-Yann [Tri-Service General Hospital, PET Center, Department of Nuclear Medicine, Taipei (China); University of Pennsylvania, Department of Radiology, Philadelphia, PA (United States)

2010-03-15

4-[{sup 18}F]-ADAM is a potent serotonin transport imaging agent. We studied its toxicity in rats and radiation dosimetry in monkeys before human studies are undertaken. Single and multiple-dosage toxicity studies were conducted in Sprague-Dawley rats. Male and female rats were injected intravenously with 4-F-ADAM as a single dose of 1,023.7 {mu}g/kg (1,000 times the human dose) or as five consecutive daily doses of 102.37 {mu}g/kg (100 times the human dose). PET/CT scans were performed in seven Formosa Rock monkeys (four males and three females) using a Siemens Biograph scanner. After injection of 4-[{sup 18}F]-ADAM (182{+-}8 MBq), a low dose CT scan and a series of eight whole-body PET scans were performed. Whole-body images were acquired in 3-D mode. Time-activity data of source organs were used to calculate the residence times and estimate the absorbed radiation dose using OLINDA/EXM software. In the rats neither the single dose nor the five daily doses of 4-F-ADAM produced overt adverse effects clinically. In the monkeys the radiation doses received by most organs ranged between 7.1 and 35.7 {mu}Gy/MBq, and the urinary bladder was considered to be the critical organ. The effective doses extrapolated to male and female adult humans were 17.4 and 21.8 {mu}Sv/MBq, respectively. Toxicity studies in Sprague-Dawley rats and radiation dosimetry studies in Formosa Rock monkeys suggested that 4-[{sup 18}F]-ADAM is safe for use in human PET imaging studies. (orig.)

Oxaliplatin-Related Ocular Toxicity

Directory of Open Access Journals (Sweden)

Marina Mesquida

2010-11-01

Full Text Available We report the case of a 52-year-old woman with advanced colorectal cancer who was treated with oxaliplatin on a FOLFOX schedule. After 3 cycles of chemotherapy, she started to complain of visual loss, altered color vision and neurological symptoms. Due to the suspicion of ocular and neurological toxicity, antineoplastic treatment was stopped. Her visual field showed a concentric bilateral scotoma and the electrooculogram test revealed severe impairment of the retinal pigment epithelium. Visual acuity, color vision and visual field recovered completely 8 months later, although electrooculogram remained abnormal. Ocular toxicity has been reported as an infrequent adverse event of oxaliplatin. Findings in this case indicate toxicity of this chemotherapeutic agent on the retinal pigment epithelium, which has not been reported before. This damage could be permanent, and it thus differs from previously described oxaliplatin-induced ocular toxicities, which are usually transient and reversible. With increasing use of oxaliplatin as first-line treatment in advanced colorectal cancer, we have to be aware of this possible toxicity.

In vitro chondrocyte toxicity following long-term, high-dose exposure to Gd-DTPA and a novel cartilage-targeted MR contrast agent

Energy Technology Data Exchange (ETDEWEB)

Midura, Sharon; Midura, Ronald J. [Cleveland Clinic, Biomedical Engineering, Lerner Research Institute, Cleveland, OH (United States); Schneider, Erika [Cleveland Clinic, Imaging Institute, A21, Cleveland, OH (United States); NitroSci Pharmaceuticals, New Berlin, WI (United States); Rosen, Gerald M. [University of Maryland School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD (United States); NitroSci Pharmaceuticals, New Berlin, WI (United States); Winalski, Carl S. [Cleveland Clinic, Biomedical Engineering, Lerner Research Institute, Cleveland, OH (United States); Cleveland Clinic, Imaging Institute, A21, Cleveland, OH (United States)

2017-01-15

To determine the concentrations exhibiting toxicity of a cartilage-targeted magnetic resonance imaging contrast agent compared with gadopentetate dimeglumine (Gd-DT-PA) in chondrocyte cultures. A long-term Swarm rat chondrosarcoma chondrocyte-like cell line was exposed for 48 h to 1.0-20 mM concentrations of diaminobutyl-linked nitroxide (DAB4-DLN) citrate, 1.0-20 mM Gd-DTPA, 1.0 μM staurosporine (positive control), or left untreated. Cell appearance, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays of metabolic activity, quantitative PicoGreen assays of DNA content, and calcein-AM viability assays were compared. At 1.0-7.5 mM, minimal decrease in cell proliferation was found for both agents. At all doses of both agents, cell culture appearances were similar after 24 h of treatment. At the higher doses, differences in cell culture appearance were found after 48 h of treatment, with dose-dependent declines in chondrocyte populations for both agents. Concentration-dependent declines in DNA content and calcein fluorescence were found after 48 h of treatment, but beginning at a lower dose of DAB4-DLN citrate than Gd-DTPA. Dose-dependent decreases in MTT staining (cell metabolism) were apparent for both agents, but larger effects were evident at a lower dose for DAB-DLN citrate. Poor MTT staining of cells exposed for 48 h to 20 mM DAB4-DLN citrate probably indicates dead or dying cells. The minimal effect of the long-term exposure of model chondrocyte cell cultures to DAB4-DLN citrate and Gd-DTPA concentrations up to 7.5 mM (3x typical arthrographic administration) is supporting evidence that these doses are acceptable for MR arthrography. The findings are reassuring given that the experimental exposure to the contrast agents at sustained concentrations was much longer than when used clinically. (orig.)

In vitro chondrocyte toxicity following long-term, high-dose exposure to Gd-DTPA and a novel cartilage-targeted MR contrast agent

International Nuclear Information System (INIS)

Midura, Sharon; Midura, Ronald J.; Schneider, Erika; Rosen, Gerald M.; Winalski, Carl S.

2017-01-01

To determine the concentrations exhibiting toxicity of a cartilage-targeted magnetic resonance imaging contrast agent compared with gadopentetate dimeglumine (Gd-DT-PA) in chondrocyte cultures. A long-term Swarm rat chondrosarcoma chondrocyte-like cell line was exposed for 48 h to 1.0-20 mM concentrations of diaminobutyl-linked nitroxide (DAB4-DLN) citrate, 1.0-20 mM Gd-DTPA, 1.0 μM staurosporine (positive control), or left untreated. Cell appearance, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays of metabolic activity, quantitative PicoGreen assays of DNA content, and calcein-AM viability assays were compared. At 1.0-7.5 mM, minimal decrease in cell proliferation was found for both agents. At all doses of both agents, cell culture appearances were similar after 24 h of treatment. At the higher doses, differences in cell culture appearance were found after 48 h of treatment, with dose-dependent declines in chondrocyte populations for both agents. Concentration-dependent declines in DNA content and calcein fluorescence were found after 48 h of treatment, but beginning at a lower dose of DAB4-DLN citrate than Gd-DTPA. Dose-dependent decreases in MTT staining (cell metabolism) were apparent for both agents, but larger effects were evident at a lower dose for DAB-DLN citrate. Poor MTT staining of cells exposed for 48 h to 20 mM DAB4-DLN citrate probably indicates dead or dying cells. The minimal effect of the long-term exposure of model chondrocyte cell cultures to DAB4-DLN citrate and Gd-DTPA concentrations up to 7.5 mM (3x typical arthrographic administration) is supporting evidence that these doses are acceptable for MR arthrography. The findings are reassuring given that the experimental exposure to the contrast agents at sustained concentrations was much longer than when used clinically. (orig.)

Arterial double-contrast dual-energy MDCT: in-vivo rabbit atherosclerosis with iodinated nanoparticles and gadolinium agents

Science.gov (United States)

Carmi, Raz; Kafri, Galit; Altman, Ami; Goshen, Liran; Planer, David; Sosna, Jacob

2010-03-01

An in-vivo feasibility study of potentially improved atherosclerosis CT imaging is presented. By administration of two different contrast agents to rabbits with induced atherosclerotic plaques we aim at identifying both soft plaque and vessel lumen simultaneously. Initial injection of iodinated nanoparticle (INP) contrast agent (N1177 - Nanoscan Imaging), two to four hours before scan, leads to its later accumulation in macrophage-rich soft plaque, while a second gadolinium contrast agent (Magnevist) injected immediately prior to the scan blends with the aortic blood. The distinction between the two agents in a single scan is achieved with a double-layer dual-energy MDCT (Philips Healthcare) following material separation analysis using the reconstructed images of the different x-ray spectra. A single contrast agent injection scan, where only INP was injected two hours prior to the scan, was compared to a double-contrast scan taken four hours after INP injection and immediately after gadolinium injection. On the single contrast agent scan we observed along the aorta walls, localized iodine accumulation which can point on INP uptake by atherosclerotic plaque. In the double-contrast scan the gadolinium contributes a clearer depiction of the vessel lumen in addition to the lasting INP presence. The material separation shows a good correlation to the pathologies inferred from the conventional CT images of the two different scans while performing only a single scan prevents miss-registration problems and reduces radiation dose. These results suggest that a double-contrast dual-energy CT may be used for advanced clinical diagnostic applications.

Complex responses to alkylating agents

International Nuclear Information System (INIS)

Samson, L.D.

2003-01-01

Using Affymetrix oligonucleotide GeneChip analysis, we previously found that, upon exposure to the simple alkylating agent methylmethane sulfonate, the transcript levels for about one third of the Saccharomyces cerevisiae genome (∼2,000 transcripts) are induced or repressed during the first hour or two after exposure. In order to determine whether the responsiveness of these genes has any relevance to the protection of cells against alkylating agents we have undertaken several follow-up studies. First, we explored the specificity of this global transcriptional response to MMS by measuring the global response of S. cerevisiae to a broad range of agents that are known to induce DNA damage. We found that each agent produced a very different mRNA transcript profile, even though the exposure doses produced similar levels of toxicity. We also found that the selection of genes that respond to MMS is highly dependent upon what cell cycle phase the cells are in at the time of exposure. Computational clustering analysis of the dataset derived from a large number of exposures identified several promoter motifs that are likely to control some of the regulons that comprise this large set of genes that are responsive to DNA damaging agents. However, it should be noted that these agents damage cellular components other than DNA, and that the responsiveness of each gene need not be in response to DNA damage per se. We have also begun to study the response of other organisms to alkylating agents, and these include E. coli, cultured mouse and human cells, and mice. Finally, we have developed a high throughput phenotypic screening method to interrogate the role of all non-essential S. cerevisiae genes (about 4,800) in protecting S. cerevisiae against the deleterious effects of alkylating agents; we have termed this analysis 'genomic phenotyping'. This study has uncovered a plethora of new pathways that play a role in the recovery of eukaryotic cells after exposure to toxic

Reversal agents in anaesthesia and critical care

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Nibedita Pani

2015-01-01

Full Text Available Despite the advent of short and ultra-short acting drugs, an in-depth knowledge of the reversal agents used is a necessity for any anaesthesiologist. Reversal agents are defined as any drug used to reverse the effects of anaesthetics, narcotics or potentially toxic agents. The controversy on the routine reversal of neuromuscular blockade still exists. The advent of newer reversal agents like sugammadex have made the use of steroidal neuromuscular blockers like rocuronium feasible in rapid sequence induction situations. We made a review of the older reversal agents and those still under investigation for drugs that are regularly used in our anaesthesia practice.

Specificity enhancement by electrospray ionization multistage mass spectrometry--a valuable tool for differentiation and identification of 'V'-type chemical warfare agents.

Science.gov (United States)

Weissberg, Avi; Tzanani, Nitzan; Dagan, Shai

2013-12-01

The use of chemical warfare agents has become an issue of emerging concern. One of the challenges in analytical monitoring of the extremely toxic 'V'-type chemical weapons [O-alkyl S-(2-dialkylamino)ethyl alkylphosphonothiolates] is to distinguish and identify compounds of similar structure. MS analysis of these compounds reveals mostly fragment/product ions representing the amine-containing residue. Hence, isomers or derivatives with the same amine residue exhibit similar mass spectral patterns in both classical EI/MS and electrospray ionization-MS, leading to unavoidable ambiguity in the identification of the phosphonate moiety. A set of five 'V'-type agents, including O-ethyl S-(2-diisopropylamino)ethyl methylphosphonothiolate (VX), O-isobutyl S-(2-diethylamino)ethyl methylphosphonothiolate (RVX) and O-ethyl S-(2-diethylamino)ethyl methylphosphonothiolate (VM) were studied by liquid chromatography/electrospray ionization/MS, utilizing a QTRAP mass detector. MS/MS enhanced product ion scans and multistage MS(3) experiments were carried out. Based on the results, possible fragmentation pathways were proposed, and a method for the differentiation and identification of structural isomers and derivatives of 'V'-type chemical warfare agents was obtained. MS/MS enhanced product ion scans at various collision energies provided information-rich spectra, although many of the product ions obtained were at low abundance. Employing MS(3) experiments enhanced the selectivity for those low abundance product ions and provided spectra indicative of the different phosphonate groups. Study of the fragmentation pathways, revealing some less expected structures, was carried out and allowed the formulation of mechanistic rules and the determination of sets of ions typical of specific groups, for example, methylphosphonothiolates versus ethylphosphonothiolates. The new group-specific ions elucidated in this work are also useful for screening unknown 'V'-type agents and related

Calcium dependence of eugenol tolerance and toxicity in Saccharomyces cerevisiae.

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Stephen K Roberts

Full Text Available Eugenol is a plant-derived phenolic compound which has recognised therapeutical potential as an antifungal agent. However little is known of either its fungicidal activity or the mechanisms employed by fungi to tolerate eugenol toxicity. A better exploitation of eugenol as a therapeutic agent will therefore depend on addressing this knowledge gap. Eugenol initiates increases in cytosolic Ca2+ in Saccharomyces cerevisiae which is partly dependent on the plasma membrane calcium channel, Cch1p. However, it is unclear whether a toxic cytosolic Ca2+elevation mediates the fungicidal activity of eugenol. In the present study, no significant difference in yeast survival was observed following transient eugenol treatment in the presence or absence of extracellular Ca2+. Furthermore, using yeast expressing apoaequorin to report cytosolic Ca2+ and a range of eugenol derivatives, antifungal activity did not appear to be coupled to Ca2+ influx or cytosolic Ca2+ elevation. Taken together, these results suggest that eugenol toxicity is not dependent on a toxic influx of Ca2+. In contrast, careful control of extracellular Ca2+ (using EGTA or BAPTA revealed that tolerance of yeast to eugenol depended on Ca2+ influx via Cch1p. These findings expose significant differences between the antifungal activity of eugenol and that of azoles, amiodarone and carvacrol. This study highlights the potential to use eugenol in combination with other antifungal agents that exhibit differing modes of action as antifungal agents to combat drug resistant infections.

Contrast agent comparison for three-dimensional micro-CT angiography: A cadaveric study.

Science.gov (United States)

Kingston, Mitchell J; Perriman, Diana M; Neeman, Teresa; Smith, Paul N; Webb, Alexandra L

2016-07-01

Barium sulfate and lead oxide contrast media are frequently used for cadaver-based angiography studies. These contrast media have not previously been compared to determine which is optimal for the visualisation and measurement of blood vessels. In this study, the lower limb vessels of 16 embalmed Wistar rats, and four sets of cannulae of known diameter, were injected with one of three different contrast agents (barium sulfate and resin, barium sulfate and gelatin, and lead oxide combined with milk powder). All were then scanned using micro-computed tomography (CT) angiography and 3-D reconstructions generated. The number of branching generations of the rat lower limb vessels were counted and compared between the contrast agents using ANOVA. The diameter of the contrast-filled cannulae, were measured and used to calculate the accuracy of the measurements by comparing the bias and variance of the estimates. Intra- and inter-observer reliability were calculated using intra-class correlation coefficients. There was no significant difference (mean difference [MD] 0.05; MD 95% confidence interval [CI] -0.83 to 0.93) between the number of branching generations for barium sulfate-resin and lead oxide-milk powder. Barium sulfate-resin demonstrated less bias and less variance of the estimates (MD 0.03; standard deviation [SD] 1.96 mm) compared to lead oxide-milk powder (MD 0.11; SD 1.96 mm) for measurements of contrast-filled cannulae scanned at high resolution. Barium sulfate-resin proved to be more accurate than lead oxide-milk powder for high resolution micro-CT scans and is preferred due to its non-toxicity. This technique could be applied to any embalmed specimen model. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Human health risk assessment database, "the NHSRC toxicity value database": supporting the risk assessment process at US EPA's National Homeland Security Research Center.

Science.gov (United States)

Moudgal, Chandrika J; Garrahan, Kevin; Brady-Roberts, Eletha; Gavrelis, Naida; Arbogast, Michelle; Dun, Sarah

2008-11-15

The toxicity value database of the United States Environmental Protection Agency's (EPA) National Homeland Security Research Center has been in development since 2004. The toxicity value database includes a compilation of agent property, toxicity, dose-response, and health effects data for 96 agents: 84 chemical and radiological agents and 12 biotoxins. The database is populated with multiple toxicity benchmark values and agent property information from secondary sources, with web links to the secondary sources, where available. A selected set of primary literature citations and associated dose-response data are also included. The toxicity value database offers a powerful means to quickly and efficiently gather pertinent toxicity and dose-response data for a number of agents that are of concern to the nation's security. This database, in conjunction with other tools, will play an important role in understanding human health risks, and will provide a means for risk assessors and managers to make quick and informed decisions on the potential health risks and determine appropriate responses (e.g., cleanup) to agent release. A final, stand alone MS ACESSS working version of the toxicity value database was completed in November, 2007.

Human health risk assessment database, 'the NHSRC toxicity value database': Supporting the risk assessment process at US EPA's National Homeland Security Research Center

International Nuclear Information System (INIS)

Moudgal, Chandrika J.; Garrahan, Kevin; Brady-Roberts, Eletha; Gavrelis, Naida; Arbogast, Michelle; Dun, Sarah

2008-01-01

The toxicity value database of the United States Environmental Protection Agency's (EPA) National Homeland Security Research Center has been in development since 2004. The toxicity value database includes a compilation of agent property, toxicity, dose-response, and health effects data for 96 agents: 84 chemical and radiological agents and 12 biotoxins. The database is populated with multiple toxicity benchmark values and agent property information from secondary sources, with web links to the secondary sources, where available. A selected set of primary literature citations and associated dose-response data are also included. The toxicity value database offers a powerful means to quickly and efficiently gather pertinent toxicity and dose-response data for a number of agents that are of concern to the nation's security. This database, in conjunction with other tools, will play an important role in understanding human health risks, and will provide a means for risk assessors and managers to make quick and informed decisions on the potential health risks and determine appropriate responses (e.g., cleanup) to agent release. A final, stand alone MS ACESSS working version of the toxicity value database was completed in November, 2007

The toxicity of uranyl nitrate on primary brain cell culture of L. Hoevenii

International Nuclear Information System (INIS)

Ismail Bahari; Fauziah Mohd Noor

1995-01-01

In Malaysia, uranium is indirectly being concentrated by mining and petroleum industries that have no relevance to its use. Concentration of uranium and the production of TENORM may give rise to radiological risk to workers and the environment. A study was conducted to determine the toxicity of a uranium compound, uranyl nitrate. For this purpose a primary brain cell culture derived from L. hoevenii was used. The nature of uranil nitrate toxicity was determined by comparing with the effects induced by mitomycin C and gamma radiation. The toxicity of these agents were measured by observing changes in Unschedule DNA Synthesis (UDS) and the induction of micronucleus. Result from the study showed that UO sub 2 sup 2+ is UDS positive and is toxic to the primary brain cells of L. hoevenii. It gives a response profile that is almost similar to that induced by gamma radiation and mitomycin C. We believed that a low concentration, UO sub 2 sup 2+ acts as a chemo toxic agent rather than as an ionising radiation. At higher concentration the toxicity of UO sub 2 sup 2+ comes from both its chemo toxic and radiation effects. Results of this study also show the ability of the primary culture to carry out repair on its DNA damaged by the UDS positive agents

Toxic-oil syndrome. Gallium-67 scanning and bronchoalveolar lavage studies in patients with abnormal lung function

International Nuclear Information System (INIS)

De la Cruz, J.L.; Oteo, L.A.; Lopez, C.; Curto, L.M.; Burgaleta, C.; Campos, A.; Sueiro, A.

1985-01-01

The toxic-oil syndrome (TOS) is a multisystem disorder whose etiology and pathogenesis are as yet unknown. Lung alterations persist in a significant number of TOS patients due to the underlying vascular lesion. Computer-assisted 67 Ga scanning and bronchoalveolar lavage (BAL) studies were performed in 14 TOS patients with sustained abnormal diffusing capacity for carbon monoxide (Dco). No significant difference was observed between the 67 Ga uptake index of the TOS and control populations. Likewise, there was no significant difference in the number of effector cells recovered from the lungs of TOS patients and controls by bronchoalveolar lavage. However, a rise in IgA and IgG concentrations (p less than 0.002) and a fall in alpha 1-antitrypsin (p less than 0.05) and transferrin (p less than 0.01) were observed in the TOS group. Phospholipid and lecithin concentrations in the lavage fluid were similar for patients and controls. The alveolar macrophage function assayed in three TOS patients was normal. These observations raise new questions about the outcome of lung pathology in TOS and warrant further follow-up studies of the lung abnormalities observed

Laboratory analysis of chemical warfare agents, adducts, and metabolites in biomedial samples

NARCIS (Netherlands)

Schans, M.J. van der

2015-01-01

Chemical warfare agents (CWAs) are the most toxic compounds ever produced. To develop medical countermeasures against the effects of these agents, analytical procedures to analyze these agents in biological matrices are essential for a better understanding of the toxicological process. The need for

Virtual Embryo: Cell-Agent Based Modeling of Developmental Processes and Toxicities (CSS BOSC)

Science.gov (United States)

Spatial regulation of cellular dynamics is fundamental to morphological development. As such, chemical disruption of spatial dynamics is a determinant of developmental toxicity. Incorporating spatial dynamics into AOPs for developmental toxicity is desired but constrained by the ...

Novel route synthesis of porous and solid gold nanoparticles for investigating their comparative performance as contrast agent in computed tomography scan and effect on liver and kidney function

Directory of Open Access Journals (Sweden)

Aziz F

2017-02-01

Full Text Available Farooq Aziz,1,2 Ayesha Ihsan,1 Aalia Nazir,2 Ishaq Ahmad,3 Sadia Zafar Bajwa,1 Asma Rehman,1 Abdoulaye Diallo,4 Waheed S Khan1 1Nanobiotechnology Group, National Institute for Biotechnology and Genetic Engineering (NIBGE, Faisalabad, 2Department of Physics, Islamia University of Bahawalpur, Bahawalpur, 3National Center for Physics, Quaid-I-Azam University, Islamabad, Pakistan; 4Laboratory of Photonics and Nano-Fabrication, Faculty of Science and Technology, Cheikh Anta Diop University of Dakar (UCAD, Dakar-Fann Dakar, Senegal Abstract: Gold nanoparticles (GNPs with dimension in the range of 1–100 nm have a prominent role in a number of biomedical applications like imaging, drug delivery, and cancer therapy owing to their unique optical features and biocompatibility. In this work, we report a novel technique for the synthesis of two types of GNPs namely porous gold nanoparticles (PGNPs and solid gold nanoparticles (SGNPs. PGNPs of size 35 nm were fabricated by reduction of gold (III solution with lecithin followed by addition of L-ascorbic acid and tri-sodium citrate, whereas SGNPs with a dimension of 28 nm were prepared by reflux method using lecithin as a single reducing agent. Comparative studies using PGNPs (λmax 560 nm and SGNPs (λmax 548 nm were conducted for evaluating their use as a contrast agent. These studies reveled that in direct computed tomography scan, PGNPs exhibited brighter contrast (45 HU than SGNPs (26 HU. To investigate the effect of PGNPs and SGNPs on the liver and kidney profile, male rabbits were intravenously injected with an equal dose of 1 mg/kg weight of PGNPs and SGNPs. The effect on biochemical parameters was evaluated 72 hours after intravenous (IV injection including liver function profile, renal (kidney function biomarker, random blood glucose value, and cholesterol level. During one comparison of contrast in CT scan, PGNPs showed significantly enhanced contrast in whole-rabbit and organ CT scan as

Anaerobic Toxicity of Cationic Silver Nanoparticles

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The microbial toxicity of silver nanoparticles (AgNPs) stabilized with different capping agents was compared to that of Ag+ under anaerobic conditions. Three AgNPs were investigated: (1) negatively charged citrate-coated AgNPs (citrate-AgNPs), (2) minimally charged p...

Environmentally safe management of radioactive and toxic sludges

International Nuclear Information System (INIS)

Shingarev, N.E.; Mukhin, I.V.; Polyakov, A.S.; Raginsky, L.S.; Semenov, B.A.

2000-01-01

Toxic industrial wastes constitute a significant part of Russian natural environment. The most reliable route to provide the long-term ecologic safety involves removal of toxicants or radioactive substances from polluted sites. With a view of processing toxic and radioactive sludges available in reservoirs, a process flowsheet is suggested that comprises the operations of sludge concentration, dehydration and granulation.Flocculation is an operation required to concentrate a solid phase. Polyacrylamide (PAA) and hydrolyzed PAA (HPAA) are standard flocculating agents used in the processing of sludges coming from storage facilities of radioactive wastes. HPAA is less efficient and it is shown that the optimized concentration of PAA is 4 mg/g solid. Flotation agents are used to extract the solid phase of sludges, it is shown that the process of extraction has to be carried out in 2 stages, the first flotation cycle with a Ph value between 7.5 and 9.5 and the second with a Ph adjustment to 3.5-6.0.The cake resulting from the sludge filtration has poor technological properties, it is advisable to produce a granular material. Hydro-granulation using hydrophobic flocculating agents may be implemented immediately after sludge concentration. The other granulation technique involves the sol-gel process used to incorporate sludge into a ceramic (aluminium oxide) matrix

Portable Sensor for Chemical Nerve Agents and Organophosphorus Compounds

Science.gov (United States)

2015-08-18

as pesticides in crop, livestock, and poultry products and as chemical and biological warfare agents. As a result of the high toxicity and the...biomedical applications such as: tissue engineering, wound dressing materials, molecular imprinting, drug delivery, etc. In this experiment the hydrogel...agents have been exploited for use as pesticides in crop, livestock, and poultry products and as chemical and biological warfare agents. As a result of

Metabolic and improved organ scan studies. II. Nitrogen-13 labeled compounds used as in-vivo probes for enzyme therapy and as tumor localizing and organ imaging agents

International Nuclear Information System (INIS)

Anon.

1976-01-01

A number of 13 N-labeled compounds have been enzymatically synthesized and are being evaluated as tumor and/or organ localizing agents. 13 N-Ammonia, produced after cyclotron generation of 13 N-nitrate and subsequent reduction was used to enzymatically aminate the appropriate substrate to yield 13 N-L-glutamic acid, L-glutamine, L-asparagine, L-valine, L-leucine and L-alanine. The use of 13 N-asparagine as a myocardial scanning agent and as a tumor localizing agent in asparaginase-sensitive tumors is discussed. Two imaging devices were used to study the effectiveness of the compounds as localizing agents. For static whole body distribution studies, a dual-detector high energy gamma ray (HEG) rectilinear scanner, equipped with constant response collimators was employed. The uniformity of response of this system permits quantitative determination of the amount of 13 N activity present in the organ or tumor of interest. The total organ kinetic imaging monitor (TOKIM) gamma camera system was used for dynamic studies covering smaller areas of the subject's body

Methoxsalen-induced macular toxicity

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Aditya Maitray

2017-01-01

Full Text Available Psoralen compounds such as methoxsalen are photosensitizer agents used in conjunction with ultraviolet A (UVA radiation exposure as photochemotherapy (Psoralens and ultraviolet-A therapy [PUVA therapy] for certain epidermal skin disorders such as psoriasis and vitiligo. Methoxsalen has been shown to be associated with premature cataract formation by forming adducts with lens proteins following oral administration and subsequent UVA exposure. Hence, the use of UV-filtering glasses is recommended during PUVA therapy sessions. Ocular tissues can be exposed to its photosensitizing effect with subsequent UV radiation exposure through sunlight if the patient was to be without protective eye glasses, potentially causing macular toxicity. Till date, there have been no reports in the literature of any posterior segment ocular toxicity arising from methoxsalen use. Here, we describe a case of a bilateral macular toxicity in a middle-aged male treated with methoxsalen for vitiligo.

Clinical aspects of percutaneous poisoning by the chemical warfare agent VX: effects of application site and decontamination.

Science.gov (United States)

Hamilton, Murray G; Hill, Ira; Conley, John; Sawyer, Thomas W; Caneva, Duane C; Lundy, Paul M

2004-11-01

O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate (VX) is an extremely toxic organophosphate nerve agent that has been weaponized and stockpiled in a number of different countries, and it has been used in recent terrorist events. It differs from other well-known organophosphate nerve agents in that its primary use is as a contact poison rather than as an inhalation hazard. For this reason, we examined the effects of application site and skin decontamination on VX toxicity in anesthetized domestic swine after topical application. VX applied to the surface of the ear rapidly resulted in signs of toxicity consistent with the development of cholinergic crisis, including apnea and death. VX on the epigastrium resulted in a marked delayed development of toxic signs, reduced toxicity, and reduction in the rate of cholinesterase depression compared with animals exposed on the ear. Skin decontamination (15 minutes post-VX on the ear) arrested the development of clinical signs and prevented further cholinesterase inhibition and death. These results confirm earlier work that demonstrates the importance of exposure site on the resultant toxicity of this agent and they also show that decontamination postexposure has the potential to be an integral and extremely important component of medical countermeasures against this agent.

Topographic assessment of human enamel surface treated with different topical sodium fluoride agents: Scanning electron microscope consideration

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Gurlal Singh Brar

2017-01-01

Full Text Available Introduction: Continuous balanced demineralization and remineralization are natural dynamic processes in enamel. If the balance is interrupted and demineralization process dominates, it may eventually lead to the development of carious lesions in enamel and dentine. Fluoride helps control decay by enhancing remineralization and altering the structure of the tooth, making the surface less soluble. Methodology: One hundred and twenty sound human permanent incisors randomly and equally distributed into six groups as follows: Group I - Control, II - Sodium fluoride solution, III - Sodium fluoride gel, IV - Sodium fluoride varnish, V - Clinpro Tooth Crème (3M ESPE, and VI-GC Tooth Mousse Plus or MI Paste Plus. The samples were kept in artificial saliva for 12 months, and the topical fluoride agents were applied to the respective sample groups as per the manufacturer instructions. Scanning electron microscope (SEM evaluation of all the samples after 6 and 12 months was made. Results: Morphological changes on the enamel surface after application of fluoride in SEM revealed the presence of globular precipitate in all treated samples. Amorphous, globular, and crystalline structures were seen on the enamel surface of the treated samples. Clear differences were observed between the treated and untreated samples. Conclusion: Globular structures consisting of amorphous CaF2precipitates, which acted as a fluoride reservoir, were observed on the enamel surface after action of different sodium fluoride agents. CPP-ACPF (Tooth Mousse and Tricalcium phosphate with fluoride (Clinpro tooth crème are excellent delivery vehicles available in a slow release amorphous form to localize fluoride at the tooth surface.

Lysosomal Re-acidification Prevents Lysosphingolipid-Induced Lysosomal Impairment and Cellular Toxicity.

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Christopher J Folts

2016-12-01

Full Text Available Neurodegenerative lysosomal storage disorders (LSDs are severe and untreatable, and mechanisms underlying cellular dysfunction are poorly understood. We found that toxic lipids relevant to three different LSDs disrupt multiple lysosomal and other cellular functions. Unbiased drug discovery revealed several structurally distinct protective compounds, approved for other uses, that prevent lysosomal and cellular toxicities of these lipids. Toxic lipids and protective agents show unexpected convergence on control of lysosomal pH and re-acidification as a critical component of toxicity and protection. In twitcher mice (a model of Krabbe disease [KD], a central nervous system (CNS-penetrant protective agent rescued myelin and oligodendrocyte (OL progenitors, improved motor behavior, and extended lifespan. Our studies reveal shared principles relevant to several LSDs, in which diverse cellular and biochemical disruptions appear to be secondary to disruption of lysosomal pH regulation by specific lipids. These studies also provide novel protective strategies that confer therapeutic benefits in a mouse model of a severe LSD.

Toxic effects of non-steroidal anti-inflammatory agents in rats ...

African Journals Online (AJOL)

The toxicosis of some non-steroidal anti-inflammatory drugs, piroxicam, indomethacin, phenylbutazone, and aspirin, which occasionally are locally used in Nigeria as rodenticides have been evaluated in rats using changes in the serum biochemical and haematological parameters as indices of toxicity. In the study, no ...

Safety assessment of nanoparamagnetic contrast agents with different coatings for molecular MRI

Science.gov (United States)

Azizian, Gholamreza; Riyahi-Alam, Nader; Haghgoo, Soheila; Saffari, Mojtaba; Zohdiaghdam, Reza; Gorji, Ensieh

2013-04-01

Despite the wide application of gadolinium as a contrast agent for magnetic resonance imaging (MRI), there is a serious lack of information on its toxicity. Gadolinium and gadolinium oxide (Gd-oxide) are used as contrast agents for magnetic resonance imaging (MRI). There are methods for reducing toxicity of these materials, such as core nanoparticles coating or conjugating. Therefore, for toxicity evaluation, we compared the viability of commercial contrast agents in MRI (Gd-DTPA) and three nanoparticles with the same core Gd2O3 and small particulate gadolinium oxide or SPGO (DTPA. The MTT and LDH assay results showed that Gd2O3-DEG nanoparticles were more toxic than Gd-DTPA and other nanoparticles. Also, SPGO-mPEG-silane2000 was more biocompatible than other nanoparticles. The obtained results did not show any significant increase in cytotoxicity of the nanoparticles and Gd-DTPA, neither dose-dependent nor time-dependent. Therefore, DEG and PEG, due to their considerable properties and irregular sizes (different molecular weights), were selected as the useful surface covering materials of nanomagnetic particles that could reveal noticeable relaxivity and biocompatibility characteristics.

Replacement of hazardous chromium impregnating agent from silver/copper/chromium-impregnated active carbon using triethylenediamine to remove hydrogen sulfide, trichloromethane, ammonia, and sulfur dioxide.

Science.gov (United States)

Wu, Li-Chun; Chung, Ying-Chien

2009-03-01

Activated carbon (AC) is widely used as an effective adsorbent in many applications, including industrial-scale air purification systems and air filter systems in gas masks. In general, ACs without chemical impregnation are good adsorbents of organic vapors but poor adsorbents of low-molecular-weight or polar gases such as chlorine, sulfur dioxide (SO2), formaldehyde, and ammonia (NH3). Impregnated ACs modified with metallic impregnating agents (ASC-carbons; e.g., copper, chromium, and silver) enhance the adsorbing properties of the ACs for simultaneously removing specific poisonous gases, but disposal of the chromium metal salt used to impregnate the ACs has the potential to result in situations that are toxic to both humans and the environment, thereby necessitating the search for replaceable organic impregnating agents that represent a much lower risk. The aim of this study was to assess the gas removal efficiency of an AC in which the organic impregnating agent triethylenediamine (TEDA) largely replaced the metallic impregnating agent chromium. We assessed batch and continuous adsorption capacities in situ for removing simulated hydrogen sulfide (H2S), trichloromethane (CHCl3), NH3, and SO2 gases. Brunauer-Emmet-Teller measurements and scanning electron microscopy analyses identified the removal mechanism by which TEDA-impregnated AS-carbon (dechromium ASC-carbon) adsorbs gases and determined the removal capacity for H2S, CHCl3, NH3, and SO2 to be 311, 258, 272, and 223 mg/g-C, respectively. These results demonstrate that TEDA-impregnated AS-carbon is significantly more efficient than ASC-carbon in adsorbing these four gases. Organic TEDA-impregnating agents have also been proven to be a reliable and environmental friendly agent and therefore a safe replacement of the hazardous chromium found in conventional ASC-carbon used in removing toxic gases from the airstream.

Medical Applications and Toxicities of Gallium Compounds

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Christopher R. Chitambar

2010-05-01

Full Text Available Over the past two to three decades, gallium compounds have gained importance in the fields of medicine and electronics. In clinical medicine, radioactive gallium and stable gallium nitrate are used as diagnostic and therapeutic agents in cancer and disorders of calcium and bone metabolism. In addition, gallium compounds have displayed anti-inflammatory and immunosuppressive activity in animal models of human disease while more recent studies have shown that gallium compounds may function as antimicrobial agents against certain pathogens. In a totally different realm, the chemical properties of gallium arsenide have led to its use in the semiconductor industry. Gallium compounds, whether used medically or in the electronics field, have toxicities. Patients receiving gallium nitrate for the treatment of various diseases may benefit from such therapy, but knowledge of the therapeutic index of this drug is necessary to avoid clinical toxicities. Animals exposed to gallium arsenide display toxicities in certain organ systems suggesting that environmental risks may exist for individuals exposed to this compound in the workplace. Although the arsenic moiety of gallium arsenide appears to be mainly responsible for its pulmonary toxicity, gallium may contribute to some of the detrimental effects in other organs. The use of older and newer gallium compounds in clinical medicine may be advanced by a better understanding of their mechanisms of action, drug resistance, pharmacology, and side-effects. This review will discuss the medical applications of gallium and its mechanisms of action, the newer gallium compounds and future directions for development, and the toxicities of gallium compounds in current use.

The toxicity of plutonium

International Nuclear Information System (INIS)

Crouse, P.L.

1994-01-01

Shipments of plutonium occasionally pass around the Cape coastal waters on its way to Japan from Europe. This invariably leads to a great deal of speculation of the dangers involved and of the extreme toxicity of plutonium, with the media and environmental groups claiming that (a) plutonium is the most toxic substance known to man, and that (b) a few kilograms of plutonium ground finely and dispersed in the atmosphere could kill every human being on earth. Comparisons with other poisons are drawn, e.g. common inorganic chemicals and biological agents. The original scare around the extraordinary toxicity of Pu seems to have started in 1974 with the claims of Tamplin and Cochran's hot particle theory about plutonium lodging in the sensitive portions of the lungs in small concentrated aggregates where they are much more effective in producing cancers. This theory, however, is regarded as thoroughly discredited by the experts in the field of radiotoxicity. 8 refs

heavy metal fixation in contaminated soil using non-toxic agents

African Journals Online (AJOL)

USER

2013-05-08

May 8, 2013 ... agricultural ecosystems (Chukwuka and Omotayo,. 2008), as well as remediation of former industrial sites which have been exposed to diffuse pollution by toxic heavy metals (Finžgar et al., 2006; Belviso et al., 2010). Among the remediation technologies available for contaminated sites, in situ (in place) ...

Toxicity assessment of molecularly targeted drugs incorporated into multiagent chemotherapy regimens for pediatric acute lymphocytic leukemia (ALL): review from an international consensus conference.

Science.gov (United States)

Horton, Terzah M; Sposto, Richard; Brown, Patrick; Reynolds, C Patrick; Hunger, Stephen P; Winick, Naomi J; Raetz, Elizabeth A; Carroll, William L; Arceci, Robert J; Borowitz, Michael J; Gaynon, Paul S; Gore, Lia; Jeha, Sima; Maurer, Barry J; Siegel, Stuart E; Biondi, Andrea; Kearns, Pamela R; Narendran, Aru; Silverman, Lewis B; Smith, Malcolm A; Zwaan, C Michel; Whitlock, James A

2010-07-01

One of the challenges of incorporating molecularly targeted drugs into multi-agent chemotherapy (backbone) regimens is defining dose-limiting toxicities (DLTs) of the targeted agent against the background of toxicities of the backbone regimen. An international panel of 22 pediatric acute lymphocytic leukemia (ALL) experts addressed this issue (www.ALLNA.org). Two major questions surrounding DLT assessment were explored: (1) how toxicities can be best defined, assessed, and attributed; and (2) how effective dosing of new agents incorporated into multi-agent ALL clinical trials can be safely established in the face of disease- and therapy-related systemic toxicities. The consensus DLT definition incorporates tolerance of resolving Grade 3 and some resolving Grade 4 toxicities with stringent safety monitoring. This functional DLT definition is being tested in two Children's Oncology Group (COG) ALL clinical trials. Copyright 2010 Wiley-Liss, Inc.

Novel route synthesis of porous and solid gold nanoparticles for investigating their comparative performance as contrast agent in computed tomography scan and effect on liver and kidney function.

Science.gov (United States)

Aziz, Farooq; Ihsan, Ayesha; Nazir, Aalia; Ahmad, Ishaq; Bajwa, Sadia Zafar; Rehman, Asma; Diallo, Abdoulaye; Khan, Waheed S

2017-01-01

Gold nanoparticles (GNPs) with dimension in the range of 1-100 nm have a prominent role in a number of biomedical applications like imaging, drug delivery, and cancer therapy owing to their unique optical features and biocompatibility. In this work, we report a novel technique for the synthesis of two types of GNPs namely porous gold nanoparticles (PGNPs) and solid gold nanoparticles (SGNPs). PGNPs of size 35 nm were fabricated by reduction of gold (III) solution with lecithin followed by addition of L-ascorbic acid and tri-sodium citrate, whereas SGNPs with a dimension of 28 nm were prepared by reflux method using lecithin as a single reducing agent. Comparative studies using PGNPs (λ max 560 nm) and SGNPs (λ max 548 nm) were conducted for evaluating their use as a contrast agent. These studies reveled that in direct computed tomography scan, PGNPs exhibited brighter contrast (45 HU) than SGNPs (26 HU). To investigate the effect of PGNPs and SGNPs on the liver and kidney profile, male rabbits were intravenously injected with an equal dose of 1 mg/kg weight of PGNPs and SGNPs. The effect on biochemical parameters was evaluated 72 hours after intravenous (IV) injection including liver function profile, renal (kidney) function biomarker, random blood glucose value, and cholesterol level. During one comparison of contrast in CT scan, PGNPs showed significantly enhanced contrast in whole-rabbit and organ CT scan as compared to SGNPs 6 hours after injection. Our findings suggested that the novel PGNPs enhance CT scan image with higher efficacy as compared to SGNPs. The results showed that IV administration of synthesized PGNPs increases the levels of aspartate aminotransferase (AST), alkaline phosphate (ALP), serum creatinine, and blood glucose, whereas that of SGNPs increases the levels of AST, ALP, and blood glucose.

Evaluating chemical and other agent exposures for reproductive and developmental toxicity

National Research Council Canada - National Science Library

Subcommittee on Reproductive and Developmental Toxicity, Committee on Toxicology, Board on Environmental Studies and Toxicology, National Research Council

2001-01-01

.... As part of its efforts to reduce or eliminate exposure of Naval personnel and their families to reproductive and developmental toxicants, the Navy requested that the National Research Council (NRC...

Optimal Contrast Agent Staining of Ligaments and Tendons for X-Ray Computed Tomography.

Science.gov (United States)

Balint, Richard; Lowe, Tristan; Shearer, Tom

2016-01-01

X-ray computed tomography has become an important tool for studying the microstructures of biological soft tissues, such as ligaments and tendons. Due to the low X-ray attenuation of such tissues, chemical contrast agents are often necessary to enhance contrast during scanning. In this article, the effects of using three different contrast agents--iodine potassium iodide solution, phosphotungstic acid and phosphomolybdic acid--are evaluated and compared. Porcine anterior cruciate ligaments, patellar tendons, medial collateral ligaments and lateral collateral ligaments were used as the basis of the study. Three samples of each of the four ligament/tendon types were each assigned a different contrast agent (giving a total of twelve samples), and the progression of that agent through the tissue was monitored by performing a scan every day for a total period of five days (giving a total of sixty scans). Since the samples were unstained on day one, they had been stained for a total of four days by the time of the final scans. The relative contrast enhancement and tissue deformation were measured. It was observed that the iodine potassium iodide solution penetrated the samples fastest and caused the least sample shrinkage on average (although significant deformation was observed by the time of the final scans), whereas the phosphomolybdic acid caused the greatest sample shrinkage. Equations describing the observed behaviour of the contrast agents, which can be used to predict optimal staining times for ligament and tendon X-ray computed tomography, are presented.

Magnesium Oxide Nanoparticles: Effective Agricultural Antibacterial Agent Against Ralstonia solanacearum

Directory of Open Access Journals (Sweden)

Lin Cai

2018-04-01

Full Text Available Magnesium (Mg is an essential mineral element for plants and is nontoxic to organisms. In this study, we took advantage of nanotechnologies to systematically investigate the antibacterial mechanisms of magnesium oxide nanoparticles (MgONPs against the phytopathogen Ralstonia solanacearum (R. solanacearum in vitro and in vivo for the first time. R. solanacearum has contributed to catastrophic bacterial wilt, which has resulted in the world-wide reduction of tobacco production. The results demonstrated that MgONPs possessed statistically significant concentration-dependent antibacterial activity, and the minimum inhibitory concentration (MIC and minimum bactericidal concentration (MBC were measured as 200 and 250 μg/mL, respectively. Additional studies, aimed at understanding the toxicity mechanism of MgONPs, indicated that physical injury occurred to the cell membranes, along with decreased motility and biofilm formation ability of R. solanacearum, due to the direct attachment of MgONPs to the surfaces of the bacterial cells, which was observed by scanning electron microscopy (SEM and transmission electron microscopy (TEM. Reactive oxygen species (ROS accumulation could also be an important reason for the antibacterial action, inducing DNA damage. The toxicity assessment assay under greenhouse conditions demonstrated that the MgONPs had exerted a large effect on tobacco bacterial wilt, reducing the bacterial wilt index. Altogether, the results suggest that the development of MgONPs as alternative antibacterial agents will become a new research subject.

Review of actinide decorporation with chelating agents

Energy Technology Data Exchange (ETDEWEB)

Ansoborlo, E. [CEA Valrho, Dir. de l' Energie Nucleaire (DEN/DRCP/CETAMA), 30 - Marcoule (France); Amekraz, B.; Moulin, Ch. [CEA Saclay, Dept. de Physico-Chimie (DEN/DPC/SECR), 91 - Gif sur Yvette (France); Moulin, V. [CEA Saclay, Dir. du Developpement et de l' Innovation Nucleares (DEN/DDIN/MR), 91 - Gif Sur Yvette (France); Taran, F. [CEA Saclay (DSV/DBJC/SMMCB), 91 - Gif-sur-Yvette (France); Bailly, Th.; Burgada, R. [Centre National de la Recherche Scientifique (CNRS/LCSB/UMR 7033), 93 - Bobigny (France); Henge-Napoli, M.H. [CEA Valrho, Site de Marcoule (INSTN), 30 (France); Jeanson, A.; Den Auwer, Ch.; Bonin, L.; Moisy, Ph. [CEA Valrho, Dir. de l' Energie Nucleaire (DEN/DRCP/SCPS), 30 - Marcoule (France)

2007-10-15

In case of accidental release of radionuclides in a nuclear facility or in the environment, internal contamination (inhalation, ingestion or wound) with actinides represents a severe health risk to human beings. It is therefore important to provide effective chelation therapy or decorporation to reduce acute radiation damage, chemical toxicity, and late radiation effects. Speciation governs bioavailability and toxicity of elements and it is a prerequisite tool for the design and success of new ligands or chelating agents. The purpose of this review is to present the state-of-the-art of actinide decorporation within biological media, to recall briefly actinide metabolism, to list the basic constraints of actinide-ligand for development, to describe main tools developed and used for decorporation studies, to review mainly the chelating agents tested for actinides, and finally to conclude on the future trends in this field. (authors)

Toxicity of oiled sediments treated with bioremediation agents: A shoreline experiment in Delaware, USA

International Nuclear Information System (INIS)

Mearna, A.; Doe, K.; Fisher, W.; Lee, K.; Mueller, C.

1995-01-01

Using a randomized complete block design, a battery of five pore water and sediment bioassays were used to monitor and compare toxicity among un-oiled, oiled (light Nigerian crude) and nutrient and bacteria-treated shoreline plots on a sandy beach. Tests included sea urchin fertilization, water and modified-solid phase microtox, 10-day amphipod survival and grass shrimp embryo bioassays. During the 13-week study, bioremediation treatment with nutrients and/or bacteria did not decrease toxicity relative to that in untreated plots. Results from at least one bioassay suggested that, relative to no treatment, treatment may have increased toxicity for several weeks. The least and most sensitive tests were sea urchin fertilization (pore water) and 10-day amphipod test, respectively. Coupled with chemical monitoring, the study produced a large data-base for evaluating toxic concentrations of petroleum hydrocarbons in sandy sediments

New nontoxic double information magnetic and fluorescent MRI agent

Energy Technology Data Exchange (ETDEWEB)

Kublickas, Augustinas; Rastenien, Loreta; Bloznelytė-Plėšnienė, Laima; Karalius, Nerijus [Liquid Crystals Laboratory, Institute of Science and Technology, Lithuanian University of Educational Sciences (Lithuania); Franckevinius, Marius [Institute of Physics, Center for Physical Sciences and Technology (Lithuania); Loudos, George [Technological Educational Institute of Athens (Greece); Fahmi, Amir [Materials Science, Rhein-Waal University of Applied Sciences (Germany); Vaisnoras, Rimas [Liquid Crystals Laboratory, Institute of Science and Technology, Lithuanian University of Educational Sciences (Lithuania)

2015-05-18

Today sensitivity of the MRI is not enough compared to the nuclear methods, such as positron emission tomography and single photon emission computed tomography. Challenging its extension to the nanometre scale could provide a powerful new tool for the nanosciences and nanomedicine. To achieve this potential, innovative new detection strategies are required to overcome the severe sensitivity limitations of conventional inductive detection techniques. In this regard, we perform embodiment of nanodiamonds in dendrimer matrix as additional fluorescent optical and magnetic (together with Gd (III)) imaging modalities of the MRI. New hybrid system composed of dendrimer-gadolinium Gd (III) - nanodiamond as a new contrast agent for MRI was studied. Poly(propilene-imine) PPI and poly(amidoamine) PAMAM dendrimers with fixed size of nanocavities will be used as host material to protect organism against the toxicity and also to increase relaxivity of contrast agent (resulting in the increases MRI resolution). Nanodiamond as biocompatible platform to functionalize the contrast agent will be used. This bimodal hybrid system enables to use smaller amount of the contrast agent and could permit the decrease of the lateral toxicity. This bimodal hybrid system as MRI agent is providing double information (magnetic and fluorescent) about the damaged cell.

New nontoxic double information magnetic and fluorescent MRI agent

International Nuclear Information System (INIS)

Kublickas, Augustinas; Rastenien, Loreta; Bloznelytė-Plėšnienė, Laima; Karalius, Nerijus; Franckevinius, Marius; Loudos, George; Fahmi, Amir; Vaisnoras, Rimas

2015-01-01

Today sensitivity of the MRI is not enough compared to the nuclear methods, such as positron emission tomography and single photon emission computed tomography. Challenging its extension to the nanometre scale could provide a powerful new tool for the nanosciences and nanomedicine. To achieve this potential, innovative new detection strategies are required to overcome the severe sensitivity limitations of conventional inductive detection techniques. In this regard, we perform embodiment of nanodiamonds in dendrimer matrix as additional fluorescent optical and magnetic (together with Gd (III)) imaging modalities of the MRI. New hybrid system composed of dendrimer-gadolinium Gd (III) - nanodiamond as a new contrast agent for MRI was studied. Poly(propilene-imine) PPI and poly(amidoamine) PAMAM dendrimers with fixed size of nanocavities will be used as host material to protect organism against the toxicity and also to increase relaxivity of contrast agent (resulting in the increases MRI resolution). Nanodiamond as biocompatible platform to functionalize the contrast agent will be used. This bimodal hybrid system enables to use smaller amount of the contrast agent and could permit the decrease of the lateral toxicity. This bimodal hybrid system as MRI agent is providing double information (magnetic and fluorescent) about the damaged cell.

On the Toxicity of the Aromatic Diamines and their Tetramethylcarboxylic Acid Derivatives

OpenAIRE

Gili, Pedro; Mederos, Alfredo

2000-01-01

The use of the theoretical PALLAS 3.0 program, to study the toxic behaviour of tetramethylcarboxylic acids, potential pharmaceuticals derived from o-phenylenediamines, indicates that o-phenylenediamines are highly toxic (level 1), while the tetramethycarboxylic acid derivatives (o-PhDTA and 3,4-TDTA) are slightly toxic, similar to EDTA (level 3). Therefore these ligands o-PhDTA and 3,4-TDTA, similar to EDTA, can be used as sequestering agents of toxic metals and overload of essential metals i...

A review of acrylamide toxicity and its mechanism

Directory of Open Access Journals (Sweden)

Ehsan Zamani

2017-05-01

Full Text Available Acrylamide (AA is an important industrial chemical agent that is mainly used in the production of polymers and copolymers. Recently it has been attention because of its production in the diet at high-temperature (>120 ºC processes such as cooking, frying, toasting, roasting or baking of high carbohydrate foods. According to high exposure to acrylamide, recognition of its toxic effect is necessary. Neurotoxicity, reproductive toxicity and immunotoxicity of AA were observed in several studies. There isn’t a clear mechanism that justifies this toxicity. In this study we reviewed the mechanisms of AA toxicity especially oxidative stress and apoptosis. AA can cause neurotoxicity, reproductive toxicity and genotoxicity on animal models. It showed neurotoxicity in human. We suggested the oxidative stress is the main factor for inducing of acrylamide toxicities. We advised that modifying of food processing methods can be as a good way for decreasing of AA production in foods.

Toxicity testing: the search for an in vitro alternative to animal testing.

Science.gov (United States)

May, J E; Xu, J; Morse, H R; Avent, N D; Donaldson, C

2009-01-01

Prior to introduction to the clinic, pharmaceuticals must undergo rigorous toxicity testing to ensure their safety. Traditionally, this has been achieved using in vivo animal models. However, besides ethical reasons, there is a continual drive to reduce the number of animals used for this purpose due to concerns such as the lack of concordance seen between animal models and toxic effects in humans. Adequate testing to ensure any toxic metabolites are detected can be further complicated if the agent is administered in a prodrug form, requiring a source of cytochrome P450 enzymes for metabolism. A number of sources of metabolic enzymes have been utilised in in vitro models, including cell lines, primary human tissue and liver extracts such as S9. This review examines current and new in vitro models for toxicity testing, including a new model developed within the authors' laboratory utilising HepG2 liver spheroids within a co-culture system to examine the effects of chemotherapeutic agents on other cell types.

Plant-Derived Agents for Counteracting Cisplatin-Induced Nephrotoxicity

OpenAIRE

Ojha, Shreesh; Venkataraman, Balaji; Kurdi, Amani; Mahgoub, Eglal; Sadek, Bassem; Rajesh, Mohanraj

2016-01-01

Cisplatin (CSP) is a chemotherapeutic agent commonly used to treat a variety of malignancies. The major setback with CSP treatment is that its clinical efficacy is compromised by its induction of organ toxicity, particular to the kidneys and ears. Despite the significant strides that have been made in understanding the mechanisms underlying CSP-induced renal toxicity, advances in developing renoprotective strategies are still lacking. In addition, the renoprotective approaches described in th...

Screening of Compounds Toxicity against Human Monocytic cell line-THP-1 by Flow Cytometry

Directory of Open Access Journals (Sweden)

Pick Neora

2004-01-01

Full Text Available The worldwide rapid increase in bacterial resistance to numerous antibiotics requires on-going development of new drugs to enter the market. As the development of new antibiotics is lengthy and costly, early monitoring of compound's toxicity is essential in the development of novel agents. Our interest is in a rapid, simple, high throughput screening method to assess cytotoxicity induced by potential agents. Some intracellular pathogens, such as Mycobacterium tuberculosis primary site of infection is human alveolar macrophages. Thus, evaluation of candidate drugs for macrophage toxicity is crucial. Protocols for high throughput drug toxicity screening of macrophages using flow cytometry are lacking in the literature. For this application we modified a preexisting technique, propidium iodide (PI exclusion staining and utilized it for rapid toxicity tests. Samples were prepared in 96 well plates and analyzed by flow cytometry, which allowed for rapid, inexpensive and precise assessment of compound's toxicity associated with cell death.

Sol-gel synthesis of bioactive glass porous scaffolds with addition of porogen agent; Sintese sol-gel de scaffolds porosos de vidro bioativo com adicao de agente porogenico

Energy Technology Data Exchange (ETDEWEB)

Guimaraes, F.B.A.P.; Barrioni, B.R.; Oliveira, A.C.X.; Oliveira, A.A.R.; Pereira, M.M., E-mail: fabianabapg@gmail.com [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte (Brazil). Escola de Engenharia. Dept. Engenharia Metalurgica e de Materiais

2016-10-15

The use of biomaterials capable of generating a biological response has been one of the biggest progresses in regenerative medicine, due to their ability to support growth stimulation and damaged tissue regeneration. In this context, bioceramics, particularly bioactive glass (BG), were the subject of many studies. The technique of porogen agent addition for the synthesis of scaffolds is an interesting procedure, because several types of porogen agents can be used. The aim of the present work was to obtain scaffolds using four porogen agents and to evaluate the effects that a change in treatment temperature can have on their crystallinity. Scaffolds of sol-gel bioactive glass 100S (100% SiO{sub 2}) using as porogen agents paraffin 1, paraffin 2, wax and CMC (carboxymethyl cellulose) were synthesized and characterized. As the best results were obtained with paraffin 1, scaffolds 58S (60%SiO{sub 2} -36%CaO-4%P{sub 2}O{sub 5} ) and 100S using paraffin 1 as porogen agent were prepared. The scaffolds were submitted to different treatment temperatures to evaluate the effect on their crystallinity. Pore structure was analyzed by scanning electron microscopy and micro-computed tomography. Scaffolds presented satisfactory pore size and pore size distribution, important characteristics for scaffolds because they allow cell migration, nutrient transport, vascularisation and tissue ingrowth. X-ray powder diffraction showed the amorphous nature of the scaffolds. At 900 °C, scaffolds BG 58S and 100S showed a small increase in crystallinity. BET analysis (N{sub 2} -adsorption) indicated a mesoporous structure. The specific surface area varied from 73.2 m{sup 2} /g for scaffold 58S treated at 800 °C to 331.2 m{sup 2} /g for scaffold 100S treated at 800 °C. The materials obtained showed no toxic effects by MTT cytotoxicity assays. Results showed that the development of scaffolds is possible using porogen agents, with 3D interconnected porous structure and might therefore be a

Role of environmental stress in the physiological response to chemical toxicants

International Nuclear Information System (INIS)

Gordon, C.J.

2003-01-01

Environmental physiology is the study of the physiological mechanisms that allow animals to cope with and adapt to changes in temperature, humidity, atmospheric pressure, and other natural factors of their physical environment. Nearly all toxicological and pharmacological studies are performed in resting (i.e., non exercising) experimental animals acclimatized to standard environmental conditions that are usually considered ideal to the animal's physiological well-being. These ideal test conditions are clearly not representative of the fluctuations in the natural environment encountered by humans and other animals on a day-to-day basis. It behooves the toxicologist, especially those interested in extrapolating experimental data from laboratory animals to humans, to consider how variations in the natural environment will alter physiological responses to toxicants. Temperature and exercise are the two most well-studied parameters in the fields of environmental physiology and toxicology. In general, high temperatures exacerbate the toxic effects of many environmental toxicants. Moreover, exercising subjects are generally more vulnerable to airborne toxic agents. The prospect of global warming also warrants a better assessment of how higher environmental temperatures may impact on the response of humans and other species to toxic chemicals. Hence, this paper and accompanying papers from the proceedings of a symposium focus on the salient aspects of the interaction between environmental stress and physiological response to toxic agents with particular emphasis on temperature and exercise

[Decontamination of chemical and biological warfare agents].

Science.gov (United States)

Seto, Yasuo

2009-01-01

Chemical and biological warfare agents (CBWA's) are diverse in nature; volatile acute low-molecular-weight toxic compounds, chemical warfare agents (CWA's, gaseous choking and blood agents, volatile nerve gases and blister agents, nonvolatile vomit agents and lacrymators), biological toxins (nonvolatile low-molecular-weight toxins, proteinous toxins) and microbes (bacteria, viruses, rickettsiae). In the consequence management against chemical and biological terrorism, speedy decontamination of victims, facilities and equipment is required for the minimization of the damage. In the present situation, washing victims and contaminated materials with large volumes of water is the basic way, and additionally hypochlorite salt solution is used for decomposition of CWA's. However, it still remains unsolved how to dispose large volumes of waste water, and the decontamination reagents have serious limitation of high toxicity, despoiling nature against the environments, long finishing time and non-durability in effective decontamination. Namely, the existing decontamination system is not effective, nonspecifically affecting the surrounding non-target materials. Therefore, it is the urgent matter to build up the usable decontamination system surpassing the present technologies. The symposiast presents the on-going joint project of research and development of the novel decontamination system against CBWA's, in the purpose of realizing nontoxic, fast, specific, effective and economical terrorism on-site decontamination. The projects consists of (1) establishment of the decontamination evaluation methods and verification of the existing technologies and adaptation of bacterial organophosphorus hydrolase, (2) development of adsorptive elimination technologies using molecular recognition tools, and (4) development of deactivation technologies using photocatalysis.

An Important Chemical Weapon Group: Nerve Agents

Directory of Open Access Journals (Sweden)

Hakan Yaren

2007-12-01

Full Text Available As a result of developing modern chemistry, nerve agents, which are one of the most important group of efficient chemical warfare agents, were developed just before Second World War. They generate toxic and clinical effects via inhibiting acetylcholinesterase irreversibly and causing excessive amounts of acetylcholine at cholinergic synapses in the body. Clinical symptoms are occurred as a result of affected muscarinic (stimulation of secretuar glands, miosis, breathing problems etc., nicotinic (stimulation of skeletal muscles, paralyse, tremors etc. and central nerve system (convulsions, loss of consciousness, coma etc. areas. In case of a nerve agent exposure, treatment includes the steps of ventilation, decontamination, antidotal treatment (atropine, oximes, diazepam and pyridostigmine bromide and supportive theraphy. Because of arising possibility of using chemical warfare agents due to current conjuncture of the world, medical staff should know about nerve agents, their effects and how to treat the casualties exposured to nerve agents. [TAF Prev Med Bull 2007; 6(6.000: 491-500

An Important Chemical Weapon Group: Nerve Agents

Directory of Open Access Journals (Sweden)

Hakan Yaren

2007-12-01

Full Text Available As a result of developing modern chemistry, nerve agents, which are one of the most important group of efficient chemical warfare agents, were developed just before Second World War. They generate toxic and clinical effects via inhibiting acetylcholinesterase irreversibly and causing excessive amounts of acetylcholine at cholinergic synapses in the body. Clinical symptoms are occurred as a result of affected muscarinic (stimulation of secretuar glands, miosis, breathing problems etc., nicotinic (stimulation of skeletal muscles, paralyse, tremors etc. and central nerve system (convulsions, loss of consciousness, coma etc. areas. In case of a nerve agent exposure, treatment includes the steps of ventilation, decontamination, antidotal treatment (atropine, oximes, diazepam and pyridostigmine bromide and supportive theraphy. Because of arising possibility of using chemical warfare agents due to current conjuncture of the world, medical staff should know about nerve agents, their effects and how to treat the casualties exposured to nerve agents. [TAF Prev Med Bull. 2007; 6(6: 491-500

The role of genetic background in susceptibility to chemical warfare nerve agents across rodent and non-human primate models.

Science.gov (United States)

Matson, Liana M; McCarren, Hilary S; Cadieux, C Linn; Cerasoli, Douglas M; McDonough, John H

2018-01-15

Genetics likely play a role in various responses to nerve agent exposure, as genetic background plays an important role in behavioral, neurological, and physiological responses to environmental stimuli. Mouse strains or selected lines can be used to identify susceptibility based on background genetic features to nerve agent exposure. Additional genetic techniques can then be used to identify mechanisms underlying resistance and sensitivity, with the ultimate goal of developing more effective and targeted therapies. Here, we discuss the available literature on strain and selected line differences in cholinesterase activity levels and response to nerve agent-induced toxicity and seizures. We also discuss the available cholinesterase and toxicity literature across different non-human primate species. The available data suggest that robust genetic differences exist in cholinesterase activity, nerve agent-induced toxicity, and chemical-induced seizures. Available cholinesterase data suggest that acetylcholinesterase activity differs across strains, but are limited by the paucity of carboxylesterase data in strains and selected lines. Toxicity and seizures, two outcomes of nerve agent exposure, have not been fully evaluated for genetic differences, and thus further studies are required to understand baseline strain and selected line differences. Published by Elsevier B.V.

Gut microbiota modulation of chemotherapy efficacy and toxicity.

Science.gov (United States)

Alexander, James L; Wilson, Ian D; Teare, Julian; Marchesi, Julian R; Nicholson, Jeremy K; Kinross, James M

2017-06-01

Evidence is growing that the gut microbiota modulates the host response to chemotherapeutic drugs, with three main clinical outcomes: facilitation of drug efficacy; abrogation and compromise of anticancer effects; and mediation of toxicity. The implication is that gut microbiota are critical to the development of personalized cancer treatment strategies and, therefore, a greater insight into prokaryotic co-metabolism of chemotherapeutic drugs is now required. This thinking is based on evidence from human, animal and in vitro studies that gut bacteria are intimately linked to the pharmacological effects of chemotherapies (5-fluorouracil, cyclophosphamide, irinotecan, oxaliplatin, gemcitabine, methotrexate) and novel targeted immunotherapies such as anti-PD-L1 and anti-CLTA-4 therapies. The gut microbiota modulate these agents through key mechanisms, structured as the 'TIMER' mechanistic framework: Translocation, Immunomodulation, Metabolism, Enzymatic degradation, and Reduced diversity and ecological variation. The gut microbiota can now, therefore, be targeted to improve efficacy and reduce the toxicity of current chemotherapy agents. In this Review, we outline the implications of pharmacomicrobiomics in cancer therapeutics and define how the microbiota might be modified in clinical practice to improve efficacy and reduce the toxic burden of these compounds.

Small bowel toxicity after high dose spot scanning-based proton beam therapy for paraspinal/retroperitoneal neoplasms

Energy Technology Data Exchange (ETDEWEB)

Schneider, R.A.; Albertini, F.; Koch, T.; Ares, C.; Lomax, A.; Goitein, G. [Paul Scherrer Institute PSI, Villigen (Switzerland). Center for Proton Therapy; Vitolo, V. [Fondazione CNAO, Pavia (Italy); Hug, E.B. [Paul Scherrer Institute PSI, Villigen (Switzerland). Center for Proton Therapy; ProCure Proton Therapy Centers, New York, NY (United States)

2013-12-15

Purpose: Mesenchymal tumours require high-dose radiation therapy (RT). Small bowel (SB) dose constraints have historically limited dose delivery to paraspinal and retroperitoneal targets. This retrospective study correlated SB dose-volume histograms with side-effects after proton radiation therapy (PT). Patients and methods: Between 1997 and 2008, 31 patients (mean age 52.1 years) underwent spot scanning-based PT for paraspinal/retroperitoneal chordomas (81 %), sarcomas (16 %) and meningiom (3 %). Mean total prescribed dose was 72.3 Gy (relative biologic effectiveness, RBE) delivered in 1.8-2 Gy (RBE) fractions. Mean follow-up was 3.8 years. Based on the pretreatment planning CT, SB dose distributions were reanalysed. Results: Planning target volume (PTV) was defined as gross tumour volume (GTV) plus 5-7 mm margins. Mean PTV was 560.22 cm{sup 3}. A mean of 93.2 % of the PTV was covered by at least 90 % of the prescribed dose. SB volumes (cm{sup 3}) receiving doses of 5, 20, 30, 40, 50, 60, 70, 75 and 80 Gy (RBE) were calculated to give V5, V20, V30, V40, V50, V60, V70, V75 and V80 respectively. In 7/31 patients, PT was accomplished without any significant SB irradiation (V5 = 0). In 24/31 patients, mean maximum dose (Dmax) to SB was 64.1 Gy (RBE). Despite target doses of > 70 Gy (RBE), SB received > 50 and > 60 Gy (RBE) in only 61 and 54 % of patients, respectively. Mean SB volumes (cm{sup 3}) covered by different dose levels (Gy, RBE) were: V20 (n = 24): 45.1, V50 (n = 19): 17.7, V60 (n = 17): 7.6 and V70 (n = 12): 2.4. No acute toxicity {>=} grade 2 or late SB sequelae were observed. Conclusion: Small noncircumferential volumes of SB tolerated doses in excess of 60 Gy (RBE) without any clinically-significant late adverse effects. This small retrospective study has limited statistical power but encourages further efforts with higher patient numbers to define and establish high-dose threshold models for SB toxicity in modern radiation oncology. (orig.)

Vaginal microbicides: detecting toxicities in vivo that paradoxically increase pathogen transmission

Directory of Open Access Journals (Sweden)

Abusuwwa Raed

2006-06-01

Full Text Available Abstract Background Microbicides must protect against STD pathogens without causing unacceptable toxic effects. Microbicides based on nonoxynol-9 (N9 and other detergents disrupt sperm, HSV and HIV membranes, and these agents are effective contraceptives. But paradoxically N9 fails to protect women against HIV and other STD pathogens, most likely because it causes toxic effects that increase susceptibility. The mouse HSV-2 vaginal transmission model reported here: (a Directly tests for toxic effects that increase susceptibility to HSV-2, (b Determines in vivo whether a microbicide can protect against HSV-2 transmission without causing toxicities that increase susceptibility, and (c Identifies those toxic effects that best correlate with the increased HSV susceptibility. Methods Susceptibility was evaluated in progestin-treated mice by delivering a low-dose viral inoculum (0.1 ID50 at various times after delivering the candidate microbicide to detect whether the candidate increased the fraction of mice infected. Ten agents were tested – five detergents: nonionic (N9, cationic (benzalkonium chloride, BZK, anionic (sodium dodecylsulfate, SDS, the pair of detergents in C31G (C14AO and C16B; one surface active agent (chlorhexidine; two non-detergents (BufferGel®, and sulfonated polystyrene, SPS; and HEC placebo gel (hydroxyethylcellulose. Toxic effects were evaluated by histology, uptake of a 'dead cell' dye, colposcopy, enumeration of vaginal macrophages, and measurement of inflammatory cytokines. Results A single dose of N9 protected against HSV-2 for a few minutes but then rapidly increased susceptibility, which reached maximum at 12 hours. When applied at the minimal concentration needed for brief partial protection, all five detergents caused a subsequent increase in susceptibility at 12 hours of ~20–30-fold. Surprisingly, colposcopy failed to detect visible signs of the N9 toxic effect that increased susceptibility at 12 hours. Toxic

Preparation and mechanism analysis of an environment-friendly maize seed coating agent.

Science.gov (United States)

Zeng, Defang; Fan, Zhao; Tian, Xu; Wang, Wenjin; Zhou, Mingchun; Li, Haochuan

2018-06-01

Traditional seed coating agents often contain toxic ingredients, which contaminate the environment and threaten human health. This paper expounds a method of preparing a novel environment-friendly seed coating agent for maize and researches its mechanism of action. The natural polysaccharide polymer, which is the main active ingredient of this environment-friendly seed coating agent, has the characteristics of innocuity and harmlessness, and it can replace the toxic ingredients used in traditional seed coating agents. This environment-friendly seed coating agent for maize was mainly made up of the natural polysaccharide polymer and other additives. The field trials results showed that the control efficacy of Helminthosporium maydis came to 93.72%, the anti-feeding rate of cutworms came to 81.29%, and the maize yield was increased by 17.75%. Besides, the LD 50 value (half the lethal dose in rats) of this seed coating agent was 10 times higher than that of the traditional seed coating agents. This seed coating agent could improve the activity of plant protective enzymes (peroxidase, catalase and superoxidase dismutase) and increase the chlorophyll content. This seed coating agent has four characteristics of disease prevention, desinsectization, increasing yield and safety. Results of mechanism analyses showed that this seed coating agent could enhance disease control effectiveness by improving plant protective enzymes activity and increase maize yield by improving chlorophyll content. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

The effectiveness testing of oil spill-treating agents

International Nuclear Information System (INIS)

Fingas, M.F.; Kyle, D.A.; Laroche, N.; Fieldhouse, B.; Sergy, G.; Stoodley, G.

1995-01-01

Laboratory effectiveness tests have been developed for four classes of oil spill treating agents: solidifiers, demulsifying agents, surface-washing agents and dispersants. Several treating agent products in these four categories have been tested for effectiveness. The aquatic toxicity of these agents is an important factor and has been measured for many products. These results are presented. Solidifiers or gelling agents solidify oil. Test results show that solidifiers require between 16% and 200% of agent by weight compared to the oil. De-emulsifying agents or emulsion breakers prevent the formation of or break water-in-oil emulsions. Surfactant-containing materials are of two types, surface-washing agents and dispersants. Testing has shown that effectiveness is orthogonal for these two types of treating agents. Tests of surface washing agents show that only a few agents have effectiveness of 25 to 55%, where this is defined as the percentage of oil removed from a test surface. Dispersant effectiveness results using the swirling flask test are reported. Heavy oils show effectiveness values of about 1%, medium crudes of about 10%, light crude oils of about 30% and very light oils of about 90%

Evaluation and interpretation of maternal toxicity in Segment II studies: Issues, some answers, and data needs

International Nuclear Information System (INIS)

Rogers, John M.; Chernoff, Neil; Keen, Carl L.; Daston, George P.

2005-01-01

Biologically rational regulatory policies with regards to developmental toxicity are often based on the extrapolation of standard laboratory rodent bioassay results to the human population. Significantly contributing to the difficulty of this task is the possibility that general toxic effects on the maternal organism may affect the developing conceptus. This review examines maternal factors which may bear directly or indirectly upon developmental outcome, with emphasis on those of greatest relevance to the hazard assessment process. Standard teratology testing protocols call for top dosage levels that induce overt maternal toxicity, and the developmental effects of this toxicity (both alone, and with concurrent embryo/fetal insult) continue to present regulators with considerable interpretive difficulties. In response to these problems, there have been both research and literature review efforts dealing with the relationship of maternal and developmental toxicity. Maternally mediated developmental toxicity occurs with a number of agents, and toxicant-induced alterations in maternal physiology may affect the conceptus at dosages not causing overt maternal toxicity. Relevant studies are reviewed here, and suggestions for avenues of future research are offered including the identification of any syndromes of developmental effects occurring at maternally toxic levels irrespective of the causative agent, and experimental approaches for the characterization of maternal toxicity

The influence of active vision on the exoskeleton of intelligent agents

Science.gov (United States)

Smith, Patrice; Terry, Theodore B.

2016-04-01

Chameleonization occurs when a self-learning autonomous mobile system's (SLAMR) active vision scans the surface of which it is perched causing the exoskeleton to changes colors exhibiting a chameleon effect. Intelligent agents having the ability to adapt to their environment and exhibit key survivability characteristics of its environments would largely be due in part to the use of active vision. Active vision would allow the intelligent agent to scan its environment and adapt as needed in order to avoid detection. The SLAMR system would have an exoskeleton, which would change, based on the surface it was perched on; this is known as the "chameleon effect." Not in the common sense of the term, but from the techno-bio inspired meaning as addressed in our previous paper. Active vision, utilizing stereoscopic color sensing functionality would enable the intelligent agent to scan an object within its close proximity, determine the color scheme, and match it; allowing the agent to blend with its environment. Through the use of its' optical capabilities, the SLAMR system would be able to further determine its position, taking into account spatial and temporal correlation and spatial frequency content of neighboring structures further ensuring successful background blending. The complex visual tasks of identifying objects, using edge detection, image filtering, and feature extraction are essential for an intelligent agent to gain additional knowledge about its environmental surroundings.

Effect of water hardness on peracetic acid toxicity to zebrafish, Danio rerio, embryos

DEFF Research Database (Denmark)

Marchand, Pierre_André; Strauss, David L.; Wienke, Andreas

2013-01-01

The use of peracetic acid (PAA) in aquaculture has been suggested as an alternative therapeutic agent. Few data are available concerning fish toxicity by PAA or factors that modify this toxicity. The aim of this study was to investigate the influence of water hardness on the acute toxicity of PAA...... acidic in low hardness. In conclusion, aquaculturists using PAA should pay attention to water hardness to avoid acidosis...

Recent Advances in Decontamination of Chemical Warfare Agents

OpenAIRE

Abdul Wadood Khan; Sabna Kotta; Shahid Husain Ansari; Javed Ali; Rakesh Kumar Sharma

2013-01-01

The recent turmoil and volatile situation in many countries and the increased risk of terrorist activities have raised alarm bells for the field of defense against toxic chemical/materials. These situations poses threats to society as terrorists can take advantage of such situations to strike and cause public mayhem. A number of chemicals have the potential of being used as chemical warfare (CW) agents. CW agents could immediately kill or incapacitate the affected individuals even when they a...

Technetium 99mTc Pertechnetate Brain Scanning

International Nuclear Information System (INIS)

Rhee, Sang Min; Park, Jin Yung; Lee, Ahn Ki; Chung, Choo Il; Hong, Chang Gi; Rhee, Chong Heon; Koh, Chang Soon

1968-01-01

Technetium 99 mTc pertechnetate brain scanning were performed in 3 cases of head injury (2 chronic subdural hematomas and 1 acute epidural hematoma), 2 cases of brain abscess and 1 case of intracerebral hematoma associated with arteriovenous anomaly. In all the cases brain scintigrams showed 'hot areas.' Literatures on radioisotope scanning of intracranial lesions were briefly reviewed. With the improvement of radioisotope scanner and development of new radiopharmaceuticals brain scanning became a safe and useful screening test for diagnosis of intracranial lesions. Brain scanning can be easily performed even to a moribund patient without any discomfort and risk to the patient which are associated with cerebral angiography or pneumoencephalography. Brain scanning has been useful in diagnosis of brain tumor, brain abscess, subdural hematoma, and cerebral vascular diseases. In 80 to 90% of brain tumors positive scintigrams can be expected. Early studies were done with 203 Hg-Neohydrin or 131 I-serum albumin. With these agents, however, patients receive rather much radiation to the whole body and kidneys. In 1965 Harper introduced 99 mTc to reduce radiation dose to the patient and improve statistical variation in isotope scanning.

Dermal Toxicity Evaluation of Neutralized Chemical Agent Identification Sets (CAIS) with an Overview of the Dermal Toxicity of Vesicant Agents and their Degradation Products.

Science.gov (United States)

1996-10-01

Food and Water Consumption and Locomotor Movement in Rats, Lab Animals, 26:180-189 (1992). Mann, F.G. and Pope, W.J., "Production and Reactions of ý...and Use: t-butyl alcohol is used in the manufacture of flotation agents, flavors, perfumes, used extensively as a solvent, as a gasoline additive

Lab-on-a-chip for rapid electrochemical detection of nerve agent Sarin

DEFF Research Database (Denmark)

Tan, Hsih-Yin; Loke, Weng Keong; Nguyen, Nam-Trung

2014-01-01

This paper reports a lab-on-a-chip for the detection of Sarin nerve agent based on rapid electrochemical detection. The chemical warfare agent Sarin (C4H10FO2P, O-isopropyl methylphosphonofluoridate) is a highly toxic organophosphate that induces rapid respiratory depression, seizures and death...

The Inhalation Toxicity of VX Aerosols Assessed in the McNamara Glove Box Facility

National Research Council Canada - National Science Library

Carpin, John C; McCaskey, David A; Cameron, Kenneth P

2005-01-01

... in this facility and to serve as a benchmark for ranking the toxicity of other agents. Neat VX challenge aerosols were generated by feeding micro-liter quantities of agent from a loaded syringe to a custom-made air assist atomizer...

Tumor scanning with /sup 57/Co-bleomycin

Energy Technology Data Exchange (ETDEWEB)

Nakano, S; Hasegawa, Y; Matsuda, Minoru; Ho, T; Doi, O [Osaka Prefectural Center for Adult Diseases (Japan)

1975-06-01

The clinical application of /sup 57/Co-bleomycin as a tumor scanning radiopharmaceutical was firstly reported by Nouel and Maeda respectively. The authors conducted studies on the diagnostic significance of this tumor scanning agent and presented the results obtained in 40 patients with malignant and non malignant lesions. Six hours and 24 hours after the injection of 500 ..mu..Ci of /sup 57/Co-bleomycin, scintigrams were taken with a 3-inch scintiscanner. Positive scans were found in 20 out of 36 patients with various malignant tumors. Of 20 patients with lung cancer, positive scans were obtained in 17 cases (85%) and of 6 with breast cancer, 3 cases showed positive scans. False negative scans were obtained in another 10 cases of malignant tumors (3 cases of thyroid carcinoma, 4 cases of hepatoma, and 1 case each of gastric carcinoma, peritoneal carcinomatosis, and reticulum cell sarcoma). Of 4 patients with non malignant disease, one case of pulmonary tuberculosis showed a positive scan. In 8 cases of lung cancer and 6 of breast cancer, the relationship between the size of the excised tumor and the scintigram findings was studied. The smallest tumors detected by scintigram were 2 cm in lung cancer and 3.2 cm in breast cancer.

Lambda-cyhalothrin toxicity in quails ( Cortunix japonica ...

African Journals Online (AJOL)

Lambda-cyhalothrin LCT is the active agent present in many insecticides used to control agricultural pest in Nigeria. Garlic contains a variety of effective compounds needed to increase the welfare of livestock. This study investigates the impact of chronic toxicity of the natural pyrethrin (LCT) on wildlife sentinels and the ...

Prevalence of Rhabdomyolysis in Sympathomimetic Toxicity: a Comparison of Stimulants.

Science.gov (United States)

O'Connor, Ayrn D; Padilla-Jones, Angie; Gerkin, Richard D; Levine, Michael

2015-06-01

Synthetic cathinones have emerged as popular drugs of abuse and produce sympathomimetic toxicity. It is unknown if rhabdomyolysis occurs more frequently following the use of synthetic cathinones compared to other stimulants. This retrospective study sought to determine the prevalence of rhabdomyolysis in patients with sympathomimetic toxicity and compare rates among patients using specific agents. Patients greater than 14 years of age with sympathomimetic toxicity and detection of a stimulant agent in urine via gas chromatography-mass spectroscopy (GC-MS) were included. Patients were excluded if clinical sympathomimetic toxicity was not present, a serum creatine kinase (CK) was not measured, or urine GC-MS was not performed. Rhabdomyolysis and severe rhabdomyolysis were defined as CK > 1000 and 10,000 IU/L, respectively. Prevalence of rhabdomyolysis and severe rhabdomyolysis were reported. Logistic regression was performed to determine the relative effect in single-agent exposures of a synthetic cathinone compared to other sympathomimetics on rhabdomyolysis. A secondary outcome, a composite endpoint defined as need for mechanical ventilation, renal replacement therapy, development of compartment syndrome, or death, was also analyzed. One hundred two subjects met inclusion criteria; median age (IQR) was 32 (25-42) years with a range of 14-65 years; 74 % were male. Rhabdomyolysis occurred in 42 % (43/102) of subjects. Patients whose sympathomimetic toxicity could be ascribed to a single agent were considered for further statistical analysis and placed into four groups: methamphetamine (n = 55), synthetic cathinone (n = 19), cocaine (n = 9), and other sympathomimetic (n = 6). In 89 subjects with single stimulant exposure, the prevalence of rhabdomyolysis was as follows: synthetic cathinone, 12/19 (63 %); methamphetamine, 22/55 (40 %); cocaine, 3/9 (33 %); and other single agent, 0/6 (0 %). The occurrence of severe rhabdomyolysis (CK > 10

Morphological and chemical changes in dentin after using endodontic agents: Fourier transform Raman spectroscopy, energy-dispersive x-ray fluorescence spectrometry, and scanning electron microscopy study

Science.gov (United States)

Pascon, Fernanda Miori; Kantovitz, Kamila Rosamilia; Soares, Luís Eduardo Silva; Santo, Ana Maria do Espírito; Martin, Airton Abraha~o.; Puppin-Rontani, Regina Maria

2012-07-01

We examine the morphological and chemical changes in the pulp chamber dentin after using endodontic agents by scanning electron microscopy (SEM), Fourier transform Raman spectroscopy (FT-Raman), and micro energy-dispersive x-ray fluorescence spectrometry (μEDXRF). Thirty teeth were sectioned exposing the pulp chamber and divided by six groups (n=5): NT-no treatment; CHX-2% chlorhexidine; CHXE-2% chlorhexidine+17% EDTA E-17% EDTA; SH5-5.25% NaOCl; SH5E-5.25% NaOCl+17% EDTA. The inorganic and organic content was analyzed by FT-Raman. μEDXRF examined calcium (Ca) and phosphorus (P) content as well as Ca/P ratio. Impressions of specimens were evaluated by SEM. Data were submitted to Kruskal-Wallis and Dunn tests (pNT=SH5E>CHX>E>CHXE). CHXE and E presented the highest Ca/P ratio values compared to the other groups (p<0.05). The SEM images in the EDTA-treated groups had the highest number of open tubules. Erosion in the tubules was observed in CHX and SH5E groups. Endodontic agents change the inorganic and organic content of pulp chamber dentin. NaOCl used alone, or in association with EDTA, was the most effective agent considering chemical and morphological approaches.

Toxicity assessment of molecularly targeted drugs incorporated into multiagent chemotherapy regimens for pediatric Acute Lymphocytic Leukemia (ALL): Review from an International Consensus Conference

NARCIS (Netherlands)

T.M. Horton (Terzah); R. Sposto (Richard); P. Brown (Patrick); C.P. Reynolds (Patrick); S.P. Hunger (Stephen); N.J. Winick (Naomi); E.A. Raetz (Elizabeth); W.L. Carroll (William); R.J. Arceci (Robert); M.J. Borowitz (Michael); P.S. Gaynon (Paul); L. Gore (Lia); S. Jeha (Sima); B.J. Maurer (Barry); S.E. Siegel (Stuart); A. Biondi (Andrea); P. Kearns (Pamela); A. Narendran (Aru); L.B. Silverman (Lewis); M.A. Smith (Malcolm); C.M. Zwaan (Christian Michel); J.A. Whitlock (James)

2010-01-01

textabstractOne of the challenges of incorporating molecularly targeted drugs into multi-agent chemotherapy (backbone) regimens is defining dose-limiting toxicities (DLTs) of the targeted agent against the background of toxicities of the backbone regimen. An international panel of 22 pediatric acute

Speciation in Metal Toxicity and Metal-Based Therapeutics

Directory of Open Access Journals (Sweden)

Douglas M. Templeton

2015-04-01

Full Text Available Metallic elements, ions and compounds produce varying degrees of toxicity in organisms with which they come into contact. Metal speciation is critical to understanding these adverse effects; the adjectives “heavy” and “toxic” are not helpful in describing the biological properties of individual elements, but detailed chemical structures are. As a broad generalization, the metallic form of an element is inert, and the ionic salts are the species that show more significant bioavailability. Yet the salts and other chelates of a metal ion can give rise to quite different toxicities, as exemplified by a range of carcinogenic potential for various nickel species. Another important distinction comes when a metallic element is organified, increasing its lipophilicity and hence its ability to penetrate the blood brain barrier, as is seen, for example, with organic mercury and tin species. Some metallic elements, such as gold and platinum, are themselves useful therapeutic agents in some forms, while other species of the same element can be toxic, thus focusing attention on species interconversions in evaluating metal-based drugs. The therapeutic use of metal-chelating agents introduces new species of the target metal in vivo, and this can affect not only its desired detoxification, but also introduce a potential for further mechanisms of toxicity. Examples of therapeutic iron chelator species are discussed in this context, as well as the more recent aspects of development of chelation therapy for uranium exposure.

Magnetic resonance imaging contrast agents: Overview and perspectives

International Nuclear Information System (INIS)

Yan Guoping; Robinson, Leslie; Hogg, Peter

2007-01-01

Magnetic resonance imaging (MRI) is a non-invasive clinical imaging modality, which has become widely used in the diagnosis and/or staging of human diseases around the world. Some MRI examinations include the use of contrast agents. The categorizations of currently available contrast agents have been described according to their effect on the image, magnetic behavior and biodistribution in the body, respectively. In this field, superparamagnetic iron oxide particles and soluble paramagnetic metal chelates are two main classes of contrast agents for MRI. This review outlines the research and development of MRI contrast agents. In future, the ideal MRI contrast agent will be focused on the neutral tissue- or organ-targeting materials with high relaxivity and specificity, low toxicity and side effects, suitable long intravascular duration and excretion time, high contrast enhancement with low dose in vivo, and with minimal cost

A study on 99mTc-macroaggregated albumin as lung imaging agent

International Nuclear Information System (INIS)

Xu Rongzhu; Fan Guangyu; Liu Yinmei; Bai Suzhen

1990-01-01

A method for the preparation of macroaggregated albumin (MAA) kits labelled with 99m Tc for lung scanning is described. The tween-80 is used as both dispersing agent and stable agent in order to raise uniformity and concentration of MAA particle size, which is between 10 to 100 μm. More than 80% particles are in the range of 10-60 μm. A millilitre MAA solution contains 5.3 x 10 6 particles. The lyophilized MAA kits are stable within eight months. The unlyophilized MAA kits are stable within 51 days. The radiochemical yield is >95% and the radiochemical purity is determined by paper chromatography. In addition, centrifuge method is used in combination with micro paper chromatography, in order to obtain the percentage of 99m Tc(IV) bound to the MAA, the percentage of unreduced 'free' 99m Tc(VII) and the percentage of reduced-hydrolyzed form of 99n Tc(IV). Blank centrifuge test of the 99m Tc(IV)-Sn colloid shows that about 85% 99m Tc(IV) is found in the supernatant solution. This method is simple and rapid. After eight hours the radiochemical purity of the labelled 99m Tc-MAA sample placed at 16 deg C and 22 deg C remains >95%. The organ distribution of LACA 18-26g mice meets the standard of the same product in the US pharmacopeia. The results of the study with rabbits by scanning with γ-camera indicate that the activity in the lung of the rabbit reaches a high level between 2-3 hours after injection. The toxic test and nonsterile and nonpyrogen test are very satisfactory and meet the standard of the Chinese pharmacopeia

Modern toxic antipersonnel projectiles.

Science.gov (United States)

Gaillard, Yvan; Regenstreif, Philippe; Fanton, Laurent

2014-12-01

In the spring of 1944, Kurt von Gottberg, the SS police chief in Minsk, was shot and injured by 2 Soviet agents. Although he was only slightly injured, he died 6 hours later. The bullets were hollow and contained a crystalline white powder. They were 4-g bullets, semi-jacketed in cupronickel, containing 28 mg of aconitine. They were later known as akonitinnitratgeschosse. The Sipo (the Nazi security police) then ordered a trial with a 9-mm Parabellum cartridge containing Ditran, an anticholinergic drug with hallucinogenic properties causing intense mental confusion. In later years, QNB was used and given the NATO code BZ (3-quinuclidinyl-benzylate). It was proven that Saddam Hussein had this weapon (agent 15) manufactured and used it against the Kurds. Serbian forces used the same type of weapon in the Bosnian conflict, particularly in Srebrenica.The authors go on to list the Cold War toxic weapons developed by the KGB and the Warsaw pact countries for the discreet elimination of dissidents and proindependence leaders who had taken refuge in the West. These weapons include PSZh-13 launchers, the Troika electronic sequential pistol, and the ingenious 4-S110T captive piston system designed by the engineer Stechkin. Disguised as a cigarette case, it could fire a silent charge of potassium cyanide. This rogues gallery also includes the umbrella rigged to inject a pellet of ricin (or another phytalbumin of similar toxicity, such as abrin or crotin) that was used to assassinate the Bulgarian writer and journalist Georgi Markov on September 7, 1978, in London.During the autopsy, the discovery of a bullet burst into 4 or 5 parts has to make at once suspecting the use of a toxic substance. Toxicological analysis has to look for first and foremost aconitine, cyanide, suxamethonium, Ditran, BZ, or one of the toxic phytalbumins. The use of such complex weapons has to make suspect a powerful organization: army, secret service, terrorism. The existence of the Russian UDAR spray

Behavioral effects of nerve agents: laboratory animal models

International Nuclear Information System (INIS)

Myers, T. M.

2009-01-01

Diverse and often subtle behavioral consequences have been reported for humans exposed to nerve agents. Laboratory studies of nerve agent exposure offer rigorous control over important variables, but species other than man must be used. Nonhuman primate models offer the best means of identifying the toxic nervous system effects of nerve agent insult and the countermeasures best capable of preventing or attenuating these effects. Comprehensive behavioral models must evaluate preservation and recovery of function as well as new learning ability. The throughput and sensitivity of the tests chosen are important considerations. A few nonhuman primate studies will be discussed to elaborate recent successes, current limitations, and future directions.(author)

Toxic Elements in Food: Occurrence, Binding, and Reduction Approaches

DEFF Research Database (Denmark)

Hajeb, P.; Sloth, Jens Jørgen; Shakibazadeh, Sh

2014-01-01

Toxic elements such as mercury, arsenic, cadmium, and lead, sometimes called heavy metals, can diminish mental and central nervous system function; elicit damage to blood composition as well as the kidneys, lungs, and liver; and reduce energy levels. Food is considered one of the main routes...... of their entry into the human body. Numerous studies have been performed to examine the effects of common food processing procedures on the levels of toxic elements in food. While some studies have reported negative effects of processing, several have shown that processing practices may have a positive effect...... on the reduction of toxic elements in foodstuffs. A number of studies have also introduced protocols and suggested chemical agents that reduce the amount of toxic elements in the final food products. In this review, the reported methods employed for the reduction of toxic elements are discussed with particular...

Decontamination and Detoxification of Toxic Chemical Warfare Agents Using Polyurethane Sponges

National Research Council Canada - National Science Library

Gordon, Richard K; Gunduz, Alper T; Askins, LaTawnya Y; Strating, Simon J; Doctor, Bhupendra P; Clarkson, Edward D; Mitchelree, Larry W; Lukey, Brian; Railer, Roy; Schulz, Susan

2003-01-01

.... Another serious problem that may be encountered while caring for personnel contaminated with organophosphorus chemical warfare nerve agents is the possibility that there will be cross-contamination...

Management of skin toxicity during radiation therapy: a review of the evidence

International Nuclear Information System (INIS)

Kumar, S.; Juresic, E.; Barton, M.; Shafiq, J.

2010-01-01

Acute skin toxicity occurs in the majority of the patients undergoing radical radiotherapy. While a variety of topical agents and dressing are used to ameliorate side effects, there is minimal evidence to support their use. The aims of this study were to systematically review evidence on acute skin toxicity management and to assess the current practices in ANZ. A systematic review of the literature was conducted on studies published between 1980 and 2008. A meta-analysis was performed on articles on clinical trials reporting grade II or greater toxicity. Analyses were divided into breast (the most common site) and other sites. A survey of Radiation Oncology departments across ANZ was conducted to identify patterns of practices and compare these with the published evidence. Twenty-nine articles were reviewed. Only seven articles demonstrated statistically significant results for management of side-effects. These were for topical corticosteroids, hyaluronic acid, sucralfate, calendula, Cavilon cream (3M, St Paul, Minnesota, USA) and silver leaf dressing. Meta-analysis demonstrated statistical significance for the prophylactic use of topical agents in the management acute toxicity. The survey of departments had a low response rate but demonstrated variation in skin care practices across ANZ. A considerable number of these practices were based only on anecdotal evidence. Lack of evidence in the literature for the care of radiation skin reactions was associated with variation in practice. Only a limited number of studies have demonstrated a significant benefit of specific topical agents. There is a need for objective and prospective recording of skin toxicity to collect meaningful comparative data on which to base recommendations for practice.

Skin decontamination of G, V, H L agents by Canadian reactive skin decontaminant lotion

Energy Technology Data Exchange (ETDEWEB)

Bide, R.W.; Sawyer, T.W.; DiNinno, V.L.; Armour, S.J.; Risk, D.J.

1993-05-13

The Canadian Reactive Skin Decontaminant Lotion (RSDL) is a reactive solution designed to be applied directly to skin for the decontamination and destruction of the classical chemical warfare agents. The solvent of the RSDL is very effective in dissolving liquid agents from the skin surface and the differential solubility of agents in the RSDL and the skin strongly favors retention of agents in the lotion. The active ingredient in the RSDL reacts rapidly and completely with G-agents, V-agents, mustard Lewisite producing relatively nontoxic products. The RSDL will dissolve and destroy agent thickened with acrylate polymers. The lotion is water soluble and readily removed from the skin. Since the RSDL is water soluble, it is active against water soluble agents even at high dilutions. For water insoluble agents, the activity is reduced as the water content rises above abrasive 50% due to insolubility of the agents. Skin and eye irritancy trials indicate that the RSDL is only a mild irritant to the eyes (equivalent to a chlorinated swimming pool) and to abraded skin. Acute toxicity trials showed that large oral and intraperitoneal doses were essentially non-toxic. The RSDL was fielded by the Canadian Forces for the Gulf Conflict. The RSDL may be used in open wounds for short periods. Wound decontamination and irrigation with RSDL diluted 1:1 with isotonic saline was recommended for the Gulf conflict.

Bone scanning with technetium /sup 99m/Tc polyphosphate in tuberculous osteomyelitis

Energy Technology Data Exchange (ETDEWEB)

Fanning, A; Dierich, H; Lentle, B

1974-09-01

Bone scans in 7 patients with tuberculosis have indicated bony involvement in 3. This was unsuspected in 2 and in all 3 radiographic correlation has been obtained. The present ready availability of more modern bone scanning agents and their safety is important to remember. They provide an elegant and sensitive, if non-specific, index of bone disease.

Systemic use of tumor necrosis factor alpha as an anticancer agent

Science.gov (United States)

Roberts, Nicholas J.; Zhou, Shibin; Diaz, Luis A.; Holdhoff, Matthias

2011-01-01

Tumor necrosis factor-α (TNF-α) has been discussed as a potential anticancer agent for many years, however initial enthusiasm about its clinical use as a systemic agent was curbed due to significant toxicities and lack of efficacy. Combination of TNF-α with chemotherapy in the setting of hyperthermic isolated limb perfusion (ILP), has provided new insights into a potential therapeutic role of this agent. The therapeutic benefit from TNF-α in ILP is thought to be not only due to its direct anti-proliferative effect, but also due to its ability to increase penetration of the chemotherapeutic agents into the tumor tissue. New concepts for the use of TNF-α as a facilitator rather than as a direct actor are currently being explored with the goal to exploit the ability of this agent to increase drug delivery and to simultaneously reduce systemic toxicity. This review article provides a comprehensive overview on the published previous experience with systemic TNF-α. Data from 18 phase I and 10 phase II single agent as well as 18 combination therapy studies illustrate previously used treatment and dose schedules, response data as well as the most prominently observed adverse effects. Also discussed, based on recent preclinical data, is a potential future role of systemic TNF-α in combination with liposomal chemotherapy to facilitate increased drug uptake into tumors. PMID:22036896

Fluorescent Chemosensors for Toxic Organophosphorus Pesticides: A Review

Directory of Open Access Journals (Sweden)

Kenneth Fletcher

2010-07-01

Full Text Available Many organophosphorus (OP based compounds are highly toxic and powerful inhibitors of cholinesterases that generate serious environmental and human health concerns. Organothiophosphates with a thiophosphoryl (P=S functional group constitute a broad class of these widely used pesticides. They are related to the more reactive phosphoryl (P=O organophosphates, which include very lethal nerve agents and chemical warfare agents, such as, VX, Soman and Sarin. Unfortunately, widespread and frequent commercial use of OP-based compounds in agricultural lands has resulted in their presence as residues in crops, livestock, and poultry products and also led to their migration into aquifers. Thus, the design of new sensors with improved analyte selectivity and sensitivity is of paramount importance in this area. Herein, we review recent advances in the development of fluorescent chemosensors for toxic OP pesticides and related compounds. We also discuss challenges and progress towards the design of future chemosensors with dual modes for signal transduction.

Towards Culturally-Aware Virtual Agent Systems

DEFF Research Database (Denmark)

Endrass, Birgit; André, Elisabeth; Rehm, Matthias

2010-01-01

Globalization leads to an increase in intercultural encounters with a risk of misunderstandings due to different patterns of behavior and understanding. Learning applications have been proposed that employ virtual agents as their primary tool. Through their embodiment, learning can be done...... in a game-like environment in a more interesting way than for example learning with a textbook. The authors support the idea that virtual agents are a great opportunity for teaching cultural awareness. Realizing this, the concept of culture needs to be translated into computational models and the advantages...... of different systems using virtual agents need to be considered. Therefore, the authors reflect in this chapter on how virtual agents can help to learn about culture, scan definitions of culture from the social sciences, give an overview on how multiagent systems developed over time and classify the state...

Toxicity of silver nanoparticles in zebrafish models

Energy Technology Data Exchange (ETDEWEB)

Asharani, P V; Valiyaveettil, Suresh [Department of Chemistry, Faculty of Science, National University of Singapore, 3 Science Drive 3, 117543 (Singapore); Wu Yilian; Gong Zhiyuan [Department of Biological Sciences, National University of Singapore, Science Drive 4, 117543 (Singapore)], E-mail: chmsv@nus.edu.sg

2008-06-25

This study was initiated to enhance our insight on the health and environmental impact of silver nanoparticles (Ag-np). Using starch and bovine serum albumin (BSA) as capping agents, silver nanoparticles were synthesized to study their deleterious effects and distribution pattern in zebrafish embryos (Danio rerio). Toxicological endpoints like mortality, hatching, pericardial edema and heart rate were recorded. A concentration-dependent increase in mortality and hatching delay was observed in Ag-np treated embryos. Additionally, nanoparticle treatments resulted in concentration-dependent toxicity, typified by phenotypes that had abnormal body axes, twisted notochord, slow blood flow, pericardial edema and cardiac arrhythmia. Ag{sup +} ions and stabilizing agents showed no significant defects in developing embryos. Transmission electron microscopy (TEM) of the embryos demonstrated that nanoparticles were distributed in the brain, heart, yolk and blood of embryos as evident from the electron-dispersive x-ray analysis (EDS). Furthermore, the acridine orange staining showed an increased apoptosis in Ag-np treated embryos. These results suggest that silver nanoparticles induce a dose-dependent toxicity in embryos, which hinders normal development.

Toxicity of silver nanoparticles in zebrafish models

International Nuclear Information System (INIS)

Asharani, P V; Valiyaveettil, Suresh; Wu Yilian; Gong Zhiyuan

2008-01-01

This study was initiated to enhance our insight on the health and environmental impact of silver nanoparticles (Ag-np). Using starch and bovine serum albumin (BSA) as capping agents, silver nanoparticles were synthesized to study their deleterious effects and distribution pattern in zebrafish embryos (Danio rerio). Toxicological endpoints like mortality, hatching, pericardial edema and heart rate were recorded. A concentration-dependent increase in mortality and hatching delay was observed in Ag-np treated embryos. Additionally, nanoparticle treatments resulted in concentration-dependent toxicity, typified by phenotypes that had abnormal body axes, twisted notochord, slow blood flow, pericardial edema and cardiac arrhythmia. Ag + ions and stabilizing agents showed no significant defects in developing embryos. Transmission electron microscopy (TEM) of the embryos demonstrated that nanoparticles were distributed in the brain, heart, yolk and blood of embryos as evident from the electron-dispersive x-ray analysis (EDS). Furthermore, the acridine orange staining showed an increased apoptosis in Ag-np treated embryos. These results suggest that silver nanoparticles induce a dose-dependent toxicity in embryos, which hinders normal development

Osmotic blood-brain barrier modification: clinical documentation by enhanced CT scanning and/or radionuclide brain scanning

International Nuclear Information System (INIS)

Neuwelt, E.A.; Specht, H.D.; Howieson, J.; Haines, J.E.; Bennett, M.J.; Hill, S.A.; Frenkel, E.P.

1983-01-01

Results of initial clinical trials of brain tumor chemotherapy after osmotic blood-brain barrier disruption are promising. In general, the procedure is well tolerated. The major complication has been seizures. In this report, data are presented which indicate that the etiology of these seizures is related to the use of contrast agent (meglumine iothalamate) to monitor barrier modification. A series of 19 patients underwent a total of 85 barrier modification procedures. Documentation of barrier disruption was monitored by contrast-enhanced computed tomographic (CT) scanning, radionuclide brain scanning, or a combination of both techniques. In 56 procedures (19 patients) monitored by enhanced CT, seizures occurred a total of 10 times in eight patients. Twenty-three barrier modification procedures (in nine of these 19 patients) documented by nuclear brain scans alone, however, resulted in only one focal motor seizure in each of two patients. In eight of the 19 patients who had seizures after barrier disruption and enhanced CT scan, four subsequently had repeat procedures monitored by radionuclide scan alone. In only one of these patients was further seizure activity noted; a single focal motor seizure was observed. Clearly, the radionuclide brain scan does not have the sensitivity and spatial resolution of enhanced CT, but at present it appears safer to monitor barrier modification by this method and to follow tumor growth between barrier modifications by enhanced CT. Four illustrative cases showing methods, problems, and promising results are presented

Element-specific spectral imaging of multiple contrast agents: a phantom study

Science.gov (United States)

Panta, R. K.; Bell, S. T.; Healy, J. L.; Aamir, R.; Bateman, C. J.; Moghiseh, M.; Butler, A. P. H.; Anderson, N. G.

2018-02-01

This work demonstrates the feasibility of simultaneous discrimination of multiple contrast agents based on their element-specific and energy-dependent X-ray attenuation properties using a pre-clinical photon-counting spectral CT. We used a photon-counting based pre-clinical spectral CT scanner with four energy thresholds to measure the X-ray attenuation properties of various concentrations of iodine (9, 18 and 36 mg/ml), gadolinium (2, 4 and 8 mg/ml) and gold (2, 4 and 8 mg/ml) based contrast agents, calcium chloride (140 and 280 mg/ml) and water. We evaluated the spectral imaging performances of different energy threshold schemes between 25 to 82 keV at 118 kVp, based on K-factor and signal-to-noise ratio and ranked them. K-factor was defined as the X-ray attenuation in the K-edge containing energy range divided by the X-ray attenuation in the preceding energy range, expressed as a percentage. We evaluated the effectiveness of the optimised energy selection to discriminate all three contrast agents in a phantom of 33 mm diameter. A photon-counting spectral CT using four energy thresholds of 27, 33, 49 and 81 keV at 118 kVp simultaneously discriminated three contrast agents based on iodine, gadolinium and gold at various concentrations using their K-edge and energy-dependent X-ray attenuation features in a single scan. A ranking method to evaluate spectral imaging performance enabled energy thresholds to be optimised to discriminate iodine, gadolinium and gold contrast agents in a single spectral CT scan. Simultaneous discrimination of multiple contrast agents in a single scan is likely to open up new possibilities of improving the accuracy of disease diagnosis by simultaneously imaging multiple bio-markers each labelled with a nano-contrast agent.

3-hydroxy-2(1H)-pyridinone chelating agents

Science.gov (United States)

Raymond, K.; Xu, J.

1999-04-06

Disclosed is a series of improved chelating agents and the chelates formed from these agents, which are highly effective upon both injection and oral administration. Several of the most effective are of low toxicity. These chelating agents incorporate within their structure 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy group of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity, as well as the chemical stability towards oxidation and reduction, of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with the adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provide a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity. 2 figs.

Sol-gel synthesis of bioactive glass porous scaffolds with addition of porogen agent

International Nuclear Information System (INIS)

Guimaraes, F.B.A.P.; Barrioni, B.R.; Oliveira, A.C.X.; Oliveira, A.A.R.; Pereira, M.M.

2016-01-01

The use of biomaterials capable of generating a biological response has been one of the biggest progresses in regenerative medicine, due to their ability to support growth stimulation and damaged tissue regeneration. In this context, bioceramics, particularly bioactive glass (BG), were the subject of many studies. The technique of porogen agent addition for the synthesis of scaffolds is an interesting procedure, because several types of porogen agents can be used. The aim of the present work was to obtain scaffolds using four porogen agents and to evaluate the effects that a change in treatment temperature can have on their crystallinity. Scaffolds of sol-gel bioactive glass 100S (100% SiO 2 ) using as porogen agents paraffin 1, paraffin 2, wax and CMC (carboxymethyl cellulose) were synthesized and characterized. As the best results were obtained with paraffin 1, scaffolds 58S (60%SiO 2 -36%CaO-4%P 2 O 5 ) and 100S using paraffin 1 as porogen agent were prepared. The scaffolds were submitted to different treatment temperatures to evaluate the effect on their crystallinity. Pore structure was analyzed by scanning electron microscopy and micro-computed tomography. Scaffolds presented satisfactory pore size and pore size distribution, important characteristics for scaffolds because they allow cell migration, nutrient transport, vascularisation and tissue ingrowth. X-ray powder diffraction showed the amorphous nature of the scaffolds. At 900 °C, scaffolds BG 58S and 100S showed a small increase in crystallinity. BET analysis (N 2 -adsorption) indicated a mesoporous structure. The specific surface area varied from 73.2 m 2 /g for scaffold 58S treated at 800 °C to 331.2 m 2 /g for scaffold 100S treated at 800 °C. The materials obtained showed no toxic effects by MTT cytotoxicity assays. Results showed that the development of scaffolds is possible using porogen agents, with 3D interconnected porous structure and might therefore be a potential biomaterial for bone

High-Relaxivity MRI Contrast Agents: Where Coordination Chemistry Meets Medical Imaging

Energy Technology Data Exchange (ETDEWEB)

Werner, Eric J.; Datta, Ankona; Jocher, Christoph J.; Raymond, Kenneth N.

2008-01-15

The desire to improve and expand the scope of clinical magnetic resonance imaging (MRI) has prompted the search for contrast agents of higher efficiency. The development of better agents requires consideration of the fundamental coordination chemistry of the gadolinium(III) ion and the parameters that affect its efficacy as a proton relaxation agent. In optimizing each parameter, other practical issues such as solubility and in vivo toxicity must also be addressed, making the attainment of safe, high-relaxivity agents a challenging goal. Here we present recent advances in the field, with an emphasis on the hydroxypyridinone family of Gd{sup III} chelates.

Blaptica dubia as sentinels for exposure to chemical warfare agents - a pilot study.

Science.gov (United States)

Worek, Franz; Seeger, Thomas; Neumaier, Katharina; Wille, Timo; Thiermann, Horst

2016-11-16

The increased interest of terrorist groups in toxic chemicals and chemical warfare agents presents a continuing threat to our societies. Early warning and detection is a key component for effective countermeasures against such deadly agents. Presently available and near term solutions have a number of major drawbacks, e.g. lack of automated, remote warning and detection of primarily low volatile chemical warfare agents. An alternative approach is the use of animals as sentinels for exposure to toxic chemicals. To overcome disadvantages of vertebrates the present pilot study was initiated to investigate the suitability of South American cockroaches (Blaptica dubia) as warning system for exposure to chemical warfare nerve and blister agents. Initial in vitro experiments with nerve agents showed an increasing inhibitory potency in the order tabun - cyclosarin - sarin - soman - VX of cockroach cholinesterase. Exposure of cockroaches to chemical warfare agents resulted in clearly visible and reproducible reactions, the onset being dependent on the agent and dose. With nerve agents the onset was related to the volatility of the agents. The blister agent lewisite induced signs largely comparable to those of nerve agents while sulfur mustard exposed animals exhibited a different sequence of events. In conclusion, this first pilot study indicates that Blaptica dubia could serve as a warning system to exposure of chemical warfare agents. A cockroach-based system will not detect or identify a particular chemical warfare agent but could trigger further actions, e.g. specific detection and increased protective status. By designing appropriate boxes with (IR) motion sensors and remote control (IR) camera automated off-site warning systems could be realized. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Small molecule fluoride toxicity agonists.

Science.gov (United States)

Nelson, James W; Plummer, Mark S; Blount, Kenneth F; Ames, Tyler D; Breaker, Ronald R

2015-04-23

Fluoride is a ubiquitous anion that inhibits a wide variety of metabolic processes. Here, we report the identification of a series of compounds that enhance fluoride toxicity in Escherichia coli and Streptococcus mutans. These molecules were isolated by using a high-throughput screen (HTS) for compounds that increase intracellular fluoride levels as determined via a fluoride riboswitch reporter fusion construct. A series of derivatives were synthesized to examine structure-activity relationships, leading to the identification of compounds with improved activity. Thus, we demonstrate that small molecule fluoride toxicity agonists can be identified by HTS from existing chemical libraries by exploiting a natural fluoride riboswitch. In addition, our findings suggest that some molecules might be further optimized to function as binary antibacterial agents when combined with fluoride. Copyright © 2015 Elsevier Ltd. All rights reserved.

Behavioral toxicity of selected radioprotectors

Science.gov (United States)

Landauer, M. R.; Davis, H. D.; Kumar, K. S.; Weiss, J. F.

1992-10-01

Effective radioprotection with minimal behavioral disruption is essential for the selection of protective agents to be used in manned spaceflight. This overview summarizes the studies on the behavioral toxicity of selected radioprotectors classified as phosphorothioates (WR-2721, WR-3689), bioactive lipids (16, 16 dimethylprostaglandin E2(DiPGE2), platelet activating factor (PAF), leukotriene C4), and immunomodulators (glucan, synthetic trehalose dicorynomycolate, and interleukin-1). Behavioral toxicity was examined in laboratory mice using a locomotor activity test. For all compounds tested, there was a dose-dependent decrease in locomotor behavior that paralleled the dose-dependent increase in radioprotection. While combinations of radioprotective compounds (DiPGE2 plus WR-2721) increased radioprotection, they also decreased locomotor activity. The central nervous system stimulant, caffeine, was able to mitigate the locomotor decrement produced by WR-3689 or PAF.

L-β-N-methylamino-l-alanine (BMAA) nitrosation generates a cytotoxic DNA damaging alkylating agent: An unexplored mechanism for neurodegenerative disease.

Science.gov (United States)

Potjewyd, G; Day, P J; Shangula, S; Margison, G P; Povey, A C

2017-03-01

L-β-N-methylamino-l-alanine (BMAA) is a non-proteinic amino acid, that is neurotoxic in vitro and in animals, and is implicated in the causation of amyotrophic lateral sclerosis and parkinsonism-dementia complex (ALS-PDC) on Guam. Given that natural amino acids can be N-nitrosated to form toxic alkylating agents and the structural similarity of BMAA to other amino acids, our hypothesis was that N-nitrosation of BMAA might result in a toxic alkylating agent, providing a novel mechanistic hypothesis for BMAA action. We have chemically nitrosated BMAA with sodium nitrite to produce nitrosated BMAA (N-BMAA) which was shown to react with the alkyl-trapping agent, 4-(p-nitrobenzyl)pyridine, cause DNA strand breaks in vitro and was toxic to the human neuroblastoma cell line SH-SY5Y under conditions in which BMAA itself was minimally toxic. Our results indicate that N-BMAA is an alkylating agent and toxin suggesting a plausible and previously unrecognised mechanism for the neurotoxic effects of BMAA. Copyright © 2017 Elsevier B.V. All rights reserved.

A Novel Non-Toxic Xylene Substitute (SBO) for Histology

OpenAIRE

Kunhua, Wang; Chuming, Fan; Tao, Lai; Yanmei, Yang; Xin, Yang; Xiaoming, Zhang; Xuezhong, Guo; Xun, Lai

2011-01-01

Xylene has been generally used as a clearing and deparaffinizing agent in histology. Because of the potential toxic and flammable nature of xylene, its substitutes have been introduced into some laboratories. In this study, we introduced a novel, non-toxic xylene substitute (SBO), which was generated through a mixture of 86% of white oil No.2 and 14% of N-heptane. SBO had a high boiling point (188°C) and flash point (144°C) coupled with a scentless and decreased volatility. To compare the eff...

Contrast agent based on nano-emulsion for targeted biomedical imaging

International Nuclear Information System (INIS)

Attia, Mohamed

2016-01-01

X-ray imaging agents are essential in combination with X-ray computed tomography to improve contrast enhancement aiming at providing complete visualization of blood vessels and giving structural and functional information on lesions allowing the detection of a tumor. As well as it is fundamental tool to discriminate between healthy cells and pathogens. We successfully limit the problems presented in commercial X-ray contrast agents like poor contrasting in Fenestra VC associated with short blood circulation time and to avoid rapid renal elimination from the body as found in Xenetix (Iobitriol). We developed nontoxic and blood pool iodine-containing nano-emulsion contrast agents serving in preclinical X-ray μ-CT imaging such as, a- Tocopherol (vitamin E), Cholecalciferol (vitamin D3), Castor oil, Capmul MCMC8 oil and oleic acid. Those formulated nano emulsions were prepared by low energy spontaneous emulsification technic with slight modification for each platform. They showed new specific features rendering them promising agents in in vivo experiments as improving the balance between the efficacy and the toxicity of targeted therapeutic interventions. We investigate the effect of size and the chemical composition of the nanoparticles on their biodistribution, pharmacokinetics and toxicity. They demonstrated that the chemical structures of the droplet's cores have significant role in targeting for example vitamin E was mainly accumulated in liver and castor oil formulation was passively accumulated in spleen explaining the proof-of-concept of EPR effect. On the other hand, two different platform sizes of Cholecalciferol molecule revealing that no real impact on the pharmacokinetics and biodistribution but presented remarkable effect on the toxicity. Of particular interest is studying the effect of the surface charge of nanoparticles on their biodistribution, this is why oleic acid nano-emulsion was selected to proceed this study by presence of amphiphilic polymer

REM sleep pathways and anticholinesterase intoxication: A mechanism for nerve agent-induced, central respiratory failure.

NARCIS (Netherlands)

Kok, A.

1993-01-01

The mechanism of death following exposure to anticholinesterases, such as the highly toxic nerve agents soman and VX, and other organophosphate anticholinesterases such as the insecticide parathion, remains unclear, although evidence from nerve agent research suggests that death occurs by an

Metabolic lung scanning with N-isopropyl-I-123-p-iodoamphetamine

International Nuclear Information System (INIS)

Touya, J.; Akber, S.F.; Rashimian, J.; Bennett, L.R.

1982-01-01

The mechanisms of uptake of N-Isopropyl-I-123-p-Iodoamphetamine (IMP) in the lung was studied in dogs. It has been concluded that this amine is taken in low specificity - high capacity endothelial receptors. Competitive effect of propranolol guanethidine, amphetamine and ketanine for the binding sites of IMP in the pulmonary endothelial cells was observed. These results show that IMP can be an agent for nonparticulate lung perfusion scans as well as for metabolic lung scans

Reducing ZnO nanoparticles toxicity through silica coating

Directory of Open Access Journals (Sweden)

Sing Ling Chia

2016-10-01

Full Text Available ZnO NPs have good antimicrobial activity that can be utilized as agents to prevent harmful microorganism growth in food. However, the use of ZnO NPs as food additive is limited by the perceived high toxicity of ZnO NPs in many earlier toxicity studies. In this study, surface modification by silica coating was used to reduce the toxicity of ZnO NPs by significantly reducing the dissolution of the core ZnO NPs. To more accurately recapitulate the scenario of ingested ZnO NPs, we tested our as synthesized ZnO NPs in ingestion fluids (synthetic saliva and synthetic gastric juice to determine the possible forms of ZnO NPs in digestive system before exposing the products to colorectal cell lines. The results showed that silica coating is highly effective in reducing toxicity of ZnO NPs through prevention of the dissociation of ZnO NPs to zinc ions in both neutral and acidic condition. The silica coating however did not alter the desired antimicrobial activity of ZnO NPs to E. coli and S. aureus. Thus, silica coating offered a potential solution to improve the biocompatibility of ZnO NPs for applications such as antimicrobial agent in foods or food related products like food packaging. Nevertheless, caution remains that high concentration of silica coated ZnO NPs can still induce undesirable cytotoxicity to mammalian gut cells. This study indicated that upstream safer-by-design philosophy in nanotechnology can be very helpful in a product development.

Technetium {sup 99m}Tc Pertechnetate Brain Scanning

Energy Technology Data Exchange (ETDEWEB)

Rhee, Sang Min; Park, Jin Yung; Lee, Ahn Ki; Chung, Choo Il; Hong, Chang Gi [Capital Army Hospital, ROKA, Seoul (Korea, Republic of); Rhee, Chong Heon; Koh, Chang Soon [Radiological Research Institute, Seoul (Korea, Republic of)

1968-03-15

Technetium {sup 99}mTc pertechnetate brain scanning were performed in 3 cases of head injury (2 chronic subdural hematomas and 1 acute epidural hematoma), 2 cases of brain abscess and 1 case of intracerebral hematoma associated with arteriovenous anomaly. In all the cases brain scintigrams showed 'hot areas.' Literatures on radioisotope scanning of intracranial lesions were briefly reviewed. With the improvement of radioisotope scanner and development of new radiopharmaceuticals brain scanning became a safe and useful screening test for diagnosis of intracranial lesions. Brain scanning can be easily performed even to a moribund patient without any discomfort and risk to the patient which are associated with cerebral angiography or pneumoencephalography. Brain scanning has been useful in diagnosis of brain tumor, brain abscess, subdural hematoma, and cerebral vascular diseases. In 80 to 90% of brain tumors positive scintigrams can be expected. Early studies were done with 203 Hg-Neohydrin or {sup 131}I-serum albumin. With these agents, however, patients receive rather much radiation to the whole body and kidneys. In 1965 Harper introduced {sup 99}mTc to reduce radiation dose to the patient and improve statistical variation in isotope scanning.

Three-dimensional brain metabolic imaging in patients with toxic encephalopathy

International Nuclear Information System (INIS)

Callender, T.J.; Duhon, D.; Ristovv, M.; Morrow, L.; Subramanian, K.

1993-01-01

Thirty-three workers, ages 24 to 63, developed clinical toxic encephalopathy after exposure to neurotoxins and were studied by SPECT brain scans. Five were exposed to pesticides, 13 were acutely exposed to mixtures of solvents, 8 were chronically exposed to mixtures of hazardous wastes that contained organic solvents, 2 were acutely exposed to phosgene and other toxins, and 5 had exposures to hydrogen sulfide. Twenty-nine had neuropsychological testing and all had a medical history and physical. Of the workers who had a clinical diagnosis of toxic encephalopathy, 31 (93.9%) had abnormal SPECT brain scans with the most frequent areas of abnormality being temporal lobes (67.7%), frontal lobes (61.3%), basal ganglia (45.2%), thalamus (29.0%), parietal lobes (12.9%), motorstrip (9.68%), cerebral hemisphere (6.45%), occipital lobes (3.23%), and caudate nucleus (3.23%). Twenty-three out of 29 (79.3%) neuropsychological evaluations were abnormal. Other modalities when performed included the following percentages of abnormals: NCV, 33.3%; CPT sensory nerve testing, 91.3%, vestibular function testing, 71.4%; olfactory testing, 89.2%; sleep EEG analysis, 85.7%; EEG, 8.33%; CT, 7.14%; and MRI brain scans, 28.6%. The complex of symptoms seen in toxic encephalopathy implies dysfunction involving several CNS regions. This series of patients adds to the previous experience of brain metabolic imaging and demonstrates that certain areas of the brain are typically affected despite differences in toxin structure, that these lesions can be globally defined by SPECT/PET brain scans, that these lesions correlate well with clinical and neuropsychological testing, and that such testing is a useful adjunct to previous methods. EEG and structural brain imaging such as CT and MRI are observed to have poor sensitivity in this type of patient. 32 refs., 5 tabs

Microbial glycolipoprotein-capped silver nanoparticles as emerging antibacterial agents against cholera.

Science.gov (United States)

Gahlawat, Geeta; Shikha, Sristy; Chaddha, Baldev Singh; Chaudhuri, Saumya Ray; Mayilraj, Shanmugam; Choudhury, Anirban Roy

2016-02-01

With the increased number of cholera outbreaks and emergence of multidrug resistance in Vibrio cholerae strains it has become necessary for the scientific community to devise and develop novel therapeutic approaches against cholera. Recent studies have indicated plausibility of therapeutic application of metal nano-materials. Among these, silver nanoparticles (AgNPs) have emerged as a potential antimicrobial agent to combat infectious diseases. At present nanoparticles are mostly produced using physical or chemical techniques which are toxic and hazardous. Thus exploitation of microbial systems could be a green eco-friendly approach for the synthesis of nanoparticles having similar or even better antimicrobial activity and biocompatibility. Hence, it would be worth to explore the possibility of utilization of microbial silver nanoparticles and their conjugates as potential novel therapeutic agent against infectious diseases like cholera. The present study attempted utilization of Ochrobactrum rhizosphaerae for the production of AgNPs and focused on investigating their role as antimicrobial agents against cholera. Later the exopolymer, purified from the culture supernatant, was used for the synthesis of spherical shaped AgNPs of around 10 nm size. Further the exopolymer was characterized as glycolipoprotein (GLP). Antibacterial activity of the novel GLP-AgNPs conjugate was evaluated by minimum inhibitory concentration, XTT reduction assay, scanning electron microscopy (SEM) and growth curve analysis. SEM studies revealed that AgNPs treatment resulted in intracellular contents leakage and cell lysis. The potential of microbially synthesized nanoparticles, as novel therapeutic agents, is still relatively less explored. In fact, the present study first time demonstrated that a glycolipoprotein secreted by the O. rhizosphaerae strain can be exploited for production of AgNPs which can further be employed to treat infectious diseases. Although this type of polymer has

Modulation of the toxicity and antitumour activity of alkylating drugs by steroids.

OpenAIRE

Shepherd, R.; Harrap, K. R.

1982-01-01

The steroids prednisolone and progesterone significantly altered the therapeutic indices of the alkylating agents, nitrogen mustard, melphalan, cyclophosphamide, phenyl acetic mustard and chlorambucil. For nitrogen mustard, chlorambucil and phenyl acetic mustard, prednisolone reduced host toxicity in the rat and enhanced the antitumour effectiveness against alkylating-agent-resistant strains of the Yoshida sarcoma and Walker carcinosarcoma. Progesterone also increased the therapeutic index of...

Benzimidazole for the prevention of toxic effects of air pollutants on plants

Energy Technology Data Exchange (ETDEWEB)

Takaoka, I; Fukuda, M; Kitano, H; Shinohara, T

1974-02-02

Tobacco plants were sprayed with benzimidazole before being exposed to 30 ppM of photochemical oxidants for a period of two hours. The plants were observed 48 hours after exposure and found to have suffered no toxic effects from the oxidants. It may be concluded that benzimidazole is an effective agent for preventing the toxic effects of air pollutants, such as photochemical oxidants on plants.

ATM regulates 3-methylpurine-DNA glycosylase and promotes therapeutic resistance to alkylating agents.

Science.gov (United States)

Agnihotri, Sameer; Burrell, Kelly; Buczkowicz, Pawel; Remke, Marc; Golbourn, Brian; Chornenkyy, Yevgen; Gajadhar, Aaron; Fernandez, Nestor A; Clarke, Ian D; Barszczyk, Mark S; Pajovic, Sanja; Ternamian, Christian; Head, Renee; Sabha, Nesrin; Sobol, Robert W; Taylor, Michael D; Rutka, James T; Jones, Chris; Dirks, Peter B; Zadeh, Gelareh; Hawkins, Cynthia

2014-10-01

Alkylating agents are a first-line therapy for the treatment of several aggressive cancers, including pediatric glioblastoma, a lethal tumor in children. Unfortunately, many tumors are resistant to this therapy. We sought to identify ways of sensitizing tumor cells to alkylating agents while leaving normal cells unharmed, increasing therapeutic response while minimizing toxicity. Using an siRNA screen targeting over 240 DNA damage response genes, we identified novel sensitizers to alkylating agents. In particular, the base excision repair (BER) pathway, including 3-methylpurine-DNA glycosylase (MPG), as well as ataxia telangiectasia mutated (ATM), were identified in our screen. Interestingly, we identified MPG as a direct novel substrate of ATM. ATM-mediated phosphorylation of MPG was required for enhanced MPG function. Importantly, combined inhibition or loss of MPG and ATM resulted in increased alkylating agent-induced cytotoxicity in vitro and prolonged survival in vivo. The discovery of the ATM-MPG axis will lead to improved treatment of alkylating agent-resistant tumors. Inhibition of ATM and MPG-mediated BER cooperate to sensitize tumor cells to alkylating agents, impairing tumor growth in vitro and in vivo with no toxicity to normal cells, providing an ideal therapeutic window. ©2014 American Association for Cancer Research.

A general mechanism for intracellular toxicity of metal-containing nanoparticles

Science.gov (United States)

Sabella, Stefania; Carney, Randy P.; Brunetti, Virgilio; Malvindi, Maria Ada; Al-Juffali, Noura; Vecchio, Giuseppe; Janes, Sam M.; Bakr, Osman M.; Cingolani, Roberto; Stellacci, Francesco; Pompa, Pier Paolo

2014-05-01

The assessment of the risks exerted by nanoparticles is a key challenge for academic, industrial, and regulatory communities worldwide. Experimental evidence points towards significant toxicity for a range of nanoparticles both in vitro and in vivo. Worldwide efforts aim at uncovering the underlying mechanisms for this toxicity. Here, we show that the intracellular ion release elicited by the acidic conditions of the lysosomal cellular compartment - where particles are abundantly internalized - is responsible for the cascading events associated with nanoparticles-induced intracellular toxicity. We call this mechanism a ``lysosome-enhanced Trojan horse effect'' since, in the case of nanoparticles, the protective cellular machinery designed to degrade foreign objects is actually responsible for their toxicity. To test our hypothesis, we compare the toxicity of similar gold particles whose main difference is in the internalization pathways. We show that particles known to pass directly through cell membranes become more toxic when modified so as to be mostly internalized by endocytosis. Furthermore, using experiments with chelating and lysosomotropic agents, we found that the toxicity mechanism for different metal containing NPs (such as metallic, metal oxide, and semiconductor NPs) is mainly associated with the release of the corresponding toxic ions. Finally, we show that particles unable to release toxic ions (such as stably coated NPs, or diamond and silica NPs) are not harmful to intracellular environments.The assessment of the risks exerted by nanoparticles is a key challenge for academic, industrial, and regulatory communities worldwide. Experimental evidence points towards significant toxicity for a range of nanoparticles both in vitro and in vivo. Worldwide efforts aim at uncovering the underlying mechanisms for this toxicity. Here, we show that the intracellular ion release elicited by the acidic conditions of the lysosomal cellular compartment - where

Effectiveness and reaction networks of H2O2 vapor with NH3 gas for decontamination of the toxic warfare nerve agent, VX on a solid surface.

Science.gov (United States)

Gon Ryu, Sam; Wan Lee, Hae

2015-01-01

The nerve agent, O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX) must be promptly eliminated following its release into the environment because it is extremely toxic, can cause death within a few minutes after exposure, acts through direct skin contact as well as inhalation, and persists in the environment for several weeks after release. A mixture of hydrogen peroxide vapor and ammonia gas was examined as a decontaminant for the removal of VX on solid surfaces at ambient temperature, and the reaction products were analyzed by gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectrometry (NMR). All the VX on glass wool filter disks was found to be eliminated after 2 h of exposure to the decontaminant mixtures, and the primary decomposition product was determined to be non-toxic ethyl methylphosphonic acid (EMPA); no toxic S-[2-(diisopropylamino)ethyl] methylphosphonothioic acid (EA-2192), which is usually produced in traditional basic hydrolysis systems, was found to be formed. However, other by-products, such as toxic O-ethyl S-vinyl methylphosphonothioate and (2-diisopropylaminoethyl) vinyl disulfide, were detected up to 150 min of exposure to the decontaminant mixture; these by-products disappeared after 3 h. The two detected vinyl byproducts were identified first in this study with the decontamination system of liquid VX on solid surfaces using a mixture of hydrogen peroxide vapor and ammonia gas. The detailed decontamination reaction networks of VX on solid surfaces produced by the mixture of hydrogen peroxide vapor and ammonia gas were suggested based on the reaction products. These findings suggest that the mixture of hydrogen peroxide vapor and ammonia gas investigated in this study is an efficient decontaminant mixture for the removal of VX on solid surfaces at ambient temperature despite the formation of a toxic by-product in the reaction process.

Safety of Systemic Agents for the Treatment of Pediatric Psoriasis

DEFF Research Database (Denmark)

Bronckers, Inge M G J; Seyger, Marieke M B; West, Dennis P

2017-01-01

Importance: Use of systemic therapies for moderate to severe psoriasis in children is increasing, but comparative data on their use and toxicities are limited. Objective: To assess patterns of use and relative risks of systemic agents for moderate to severe psoriasis in children. Design, Setting,...... per week protected more against methotrexate-induced gastrointestinal AEs than did weekly administration. A prospective registry is needed to track the long-term risks of systemic agents for pediatric psoriasis....

Development and use of a new Tc-99m myocardial perfusion agent - DMPE

International Nuclear Information System (INIS)

Sodd, V.J.; Nishiyama, H.; Grossman, L.W.

1982-01-01

Thallium-201 is used routinely in nuclear medicine as a myocardial imaging agent. Because of its high cost and inferior scintigraphic and dosimetric properties as compared to Tc-99m, efforts to develop a Tc-99m myocardial imaging agent to replace Tl-201 have been underway. The development, dosimetry, toxicity and pre-clinical investigations in dogs of a new and promising Tc-99m myocardial imaging agent, Tc-DMPE, are described

A new anticancer agent--131I BGTP

International Nuclear Information System (INIS)

He Jiaheng; Jiang Shubin; Wang Guanquan

2007-12-01

A new anticancer precursor, di-peptide[p-Boc-Gly-Tyr-NH(CH 2 ) 2 NH-PO (ONH 4 )-O-PhI*], was synthesized and labelled with 131 I using enveloped-tube technique, the labelling yield could reach 85%. Using cell coalescent method, the biological activity in vitro of the labelled compounds was evaluated, showing that the primary appetency was kept and not damaged obviously during labelling. Results on judgement of their stability, lipophilicity and toxicity demonstrated lower toxicity, higher lipophilicity and lower iodium disassociation percentage (<12% after 72 h); furthermore, a tumour-bearing animal model, was establishd successfully, on which, the biological properties of the labelled agent was studied. (authors)

Comparative metal oxide nanoparticle toxicity using embryonic zebrafish

Directory of Open Access Journals (Sweden)

Leah C. Wehmas

2015-01-01

Full Text Available Engineered metal oxide nanoparticles (MO NPs are finding increasing utility in the medical field as anticancer agents. Before validation of in vivo anticancer efficacy can occur, a better understanding of whole-animal toxicity is required. We compared the toxicity of seven widely used semiconductor MO NPs made from zinc oxide (ZnO, titanium dioxide, cerium dioxide and tin dioxide prepared in pure water and in synthetic seawater using a five-day embryonic zebrafish assay. We hypothesized that the toxicity of these engineered MO NPs would depend on physicochemical properties. Significant agglomeration of MO NPs in aqueous solutions is common making it challenging to associate NP characteristics such as size and charge with toxicity. However, data from our agglomerated MO NPs suggests that the elemental composition and dissolution potential are major drivers of toxicity. Only ZnO caused significant adverse effects of all MO particles tested, and only when prepared in pure water (point estimate median lethal concentration = 3.5–9.1 mg/L. This toxicity was life stage dependent. The 24 h toxicity increased greatly (∼22.7 fold when zebrafish exposures started at the larval life stage compared to the 24 h toxicity following embryonic exposure. Investigation into whether dissolution could account for ZnO toxicity revealed high levels of zinc ion (40–89% of total sample were generated. Exposure to zinc ion equivalents revealed dissolved Zn2+ may be a major contributor to ZnO toxicity.

Chemical toxicity approach for emergency response

International Nuclear Information System (INIS)

Bauer, T.

2009-01-01

In the event of an airborne release of chemical agent or toxic industrial chemical by accidental or intentional means, emergency responders must have a reasonable estimate of the location and size of the resulting hazard area. Emergency responders are responsible for warning persons downwind of the hazard to evacuate or shelter-in-place and must know where to look for casualties after the hazard has passed or dissipated. Given the same source characterization, modern hazard assessment models provide comparable concentration versus location and time estimates. Even urban hazard assessment models often provide similar predictions. There is a major shortcoming, though, in applying model output to estimating human toxicity effects. There exist a variety of toxicity values for non-lethal effects ranging from short-term to occupational to lifetime exposures. For health and safety purposes, these estimates are all safe-sided in converting animal data to human effects and in addressing the most sensitive subset of the population. In addition, these values are usually based on an assumed 1 hour exposure duration at constant concentration and do not reflect either a passing clouds concentration profile or duration. Emergency responders need expected value toxicity parameters rather than the existing safe-sided ones. This presentation will specify the types of toxicity values needed to provide appropriate chemical hazard estimates to emergency responders and will demonstrate how dramatically their use changes the hazard area.(author)

Interaction of chelating agents with cadmium in mice and rats

International Nuclear Information System (INIS)

Eybl, V.; Sykora, J.; Koutensky, J.; Caisova, D.; Schwartz, A.; Mertl, F.

1984-01-01

The influence of several chelating agents (CaDTPA, ZnDTPA, CaEDTA, ZnEDTA, DMSA, D-penicillamine and DMPS, DMP and DDC) on the acute toxicity of CdCl 2 and on the whole body retention and tissue distribution of cadmium after the IV application of /sup 115mCdCl 2 was compared in mice. The chelating agents were applied immediately after the application of cadmium. CaDTPA, ZnDTPA and DMSA appeared to be the most effective antidotes. However, DMSA increased the amount of cadmium retained in kidneys. The treatement of cadmium-poisoned mice with the combination of DMSA (IP) and ZnDTPA (SC) (all the compounds were injected in equimolar dose) decreased the toxicity of cadmium more than treatment with one chelating agents (given in a 2:1 dose). However, by studying the effect of these chelating agents and their combination application of the antidotes showed little or no improvement over the results obtained with the most effective of the individual components. In the urine of rats injected with CdCl 2 and treated with the chelating agents (CaDTPA, ZnDTPA, DMSA), the presence of cadmium complexes was demonstrated. The formation of mixed ligand chelates in vivo was not proved. Experiments in mice given a single injection of /sup 115m/Cd-labeled Cd complexes of DMPS, DMSA and DTPA showed a high retention of cadmium in the organisms after the IV application of CdDMPS and CdDMSA complexes

Genome-Wide Mutational Signature of the Chemotherapeutic Agent Mitomycin C in Caenorhabditis elegans.

Science.gov (United States)

Tam, Annie S; Chu, Jeffrey S C; Rose, Ann M

2015-11-12

Cancer therapy largely depends on chemotherapeutic agents that generate DNA lesions. However, our understanding of the nature of the resulting lesions as well as the mutational profiles of these chemotherapeutic agents is limited. Among these lesions, DNA interstrand crosslinks are among the more toxic types of DNA damage. Here, we have characterized the mutational spectrum of the commonly used DNA interstrand crosslinking agent mitomycin C (MMC). Using a combination of genetic mapping, whole genome sequencing, and genomic analysis, we have identified and confirmed several genomic lesions linked to MMC-induced DNA damage in Caenorhabditis elegans. Our data indicate that MMC predominantly causes deletions, with a 5'-CpG-3' sequence context prevalent in the deleted regions of DNA. Furthermore, we identified microhomology flanking the deletion junctions, indicative of DNA repair via nonhomologous end joining. Based on these results, we propose a general repair mechanism that is likely to be involved in the biological response to this highly toxic agent. In conclusion, the systematic study we have described provides insight into potential sequence specificity of MMC with DNA. Copyright © 2016 Tam et al.

Genome-Wide Mutational Signature of the Chemotherapeutic Agent Mitomycin C in Caenorhabditis elegans

Directory of Open Access Journals (Sweden)

Annie S. Tam

2016-01-01

Full Text Available Cancer therapy largely depends on chemotherapeutic agents that generate DNA lesions. However, our understanding of the nature of the resulting lesions as well as the mutational profiles of these chemotherapeutic agents is limited. Among these lesions, DNA interstrand crosslinks are among the more toxic types of DNA damage. Here, we have characterized the mutational spectrum of the commonly used DNA interstrand crosslinking agent mitomycin C (MMC. Using a combination of genetic mapping, whole genome sequencing, and genomic analysis, we have identified and confirmed several genomic lesions linked to MMC-induced DNA damage in Caenorhabditis elegans. Our data indicate that MMC predominantly causes deletions, with a 5′-CpG-3′ sequence context prevalent in the deleted regions of DNA. Furthermore, we identified microhomology flanking the deletion junctions, indicative of DNA repair via nonhomologous end joining. Based on these results, we propose a general repair mechanism that is likely to be involved in the biological response to this highly toxic agent. In conclusion, the systematic study we have described provides insight into potential sequence specificity of MMC with DNA.

Making bio-sense of toxicity: new developments in whole-cell biosencors

DEFF Research Database (Denmark)

Sørensen, Søren Johannes; Burmølle, Mette; Hansen, Lars Hestbjerg

2006-01-01

Bacterial whole-cell biosensors are very useful for toxicity measurements of various samples. Semi-specific biosensors, containing fusions of stress-regulated promoters and reporter genes, have several advantages over the traditional, general biosensors that are based on constitutively expressed ....... The application of in situ inoculation and single-cell detection, combined with the introduction of new reporter genes and refined detection equipment, could lead to the extensive use of semi-specific, stress-responsive biosensors for toxicity estimations in the future....... reporter genes. Furthermore, semi-specific biosensors are constantly being refined to lower their sensitivity and, in combination, are able to detect a wide range of toxic agents. However, the requirement for a positive response of these biosensors to toxicants can result in false-negative responses...

Silver Nanoparticles: Synthetic Routes, In Vitro Toxicity and Theranostic Applications for Cancer Disease

Directory of Open Access Journals (Sweden)

Valeria De Matteis

2018-05-01

Full Text Available The large use of nanomaterials in many fields of application and commercial products highlights their potential toxicity on living organisms and the environment, despite their physico-chemical properties. Among these, silver nanoparticles (Ag NPs are involved in biomedical applications such as antibacterial agents, drug delivery vectors and theranostics agents. In this review, we explain the common synthesis routes of Ag NPs using physical, chemical, and biological methods, following their toxicity mechanism in cells. In particular, we analyzed the physiological cellular pathway perturbations in terms of oxidative stress induction, mitochondrial membrane potential alteration, cell death, apoptosis, DNA damage and cytokines secretion after Ag NPs exposure. In addition, their potential anti-cancer activity and theranostic applications are discussed.

Evaluation of liquid-phase oxidation for the destruction of potential chemical terrorism agents

Energy Technology Data Exchange (ETDEWEB)

Thouin, G.; Harrison, S.; Li, K.; Kuang, W.; Volchek, K.; Fingas, M. [Environment Canada, Ottawa, ON (Canada). Emergencies Science Div; Potaraju, S.; Velicogna, D.; Obenauf, A. [SAIC Canada, Ottawa, ON (Canada)

2005-07-01

Although pesticides are designed to protect crops and livestock against insects, fungi or nuisance plants, the toxicity of these compounds is not limited to target species. Organophosphorus, organochlorine and carbamate pesticides all target the nervous systems of insects. This paper assessed the effectiveness of an enhanced oxidation process using peroxycarboxylic acids for the liquid-phase destruction of toxic industrial chemicals, considered to be potential agents of chemical terrorism. Peroxyacetic acid (PAA) and peroxypropionic acid (PPA) were tested as decontamination agents on organophosphorus, organochlorine and carbamate pesticides. The processes were reviewed in relation to the terms of percent agent destruction over time, with a target of 90 per cent destruction within 30 minutes. Effectiveness was also assessed on the accumulation of toxic by-products. A background of the pesticides was presented, as well as details of their various applications. The molecular structures of the compounds were also provided. Oxidation extraction procedures, materials and methods were also presented, as well as analytical techniques, method detection limits and issues concerning reproducibility. The pH profile of PAA and PPA as a function of the concentration in acid was studied in order to determine which was more likely to be corrosive. It was concluded that peroxycarboxylic acids are effective decontamination agents for organophosphorous and carbamate pesticides. PAA and PPA are equally effective in degrading the examined pesticides, however, greater amounts of toxic by-products are found with PPA than with PAA. Neither PAA nor PPA were able to degrade lindane, and more lindane was found in the treated samples than in the controls. It was noted that time profiles for lower concentrations of peroxycarboxylic acids and pH profiles are currently being developed. It was suggested that further research in this area included degradation experiments on various types of

Permeation Testing of Materials With Chemical Agents or Simulants (Swatch Testing)

Science.gov (United States)

2013-08-05

nerve agents, sarin (GB), soman (GD), and persistent nerve agent (VX). These procedures can also be applied to toxic industrial chemicals (TICs...garment, cap, clothing liner, mask, glove, footwear , etc. The swatch should be selected to be representative of the area of the material to be tested...solvent and the extract analyzed. This reduces the sensitivity but obviates problems arising from one-shot thermal desorption. c. NRT and real

Labelled radioactive adenosinphosphates for the determination of toxic action

International Nuclear Information System (INIS)

Tahbaz, Z.

1983-01-01

Normal house-flies had been fed with carrier free radiophosphate (phosphorus). Many phosphorous containing substances in the tissue of the housefly are labelled with radiophosphorus by this procedure. Radiophosphorus is also found in the nucleotides of the housefly after applying radioactive phosphate. Suitable methods for processing and separation had been selected and worked out to isolate 32 P-adenosin-triphosphate 32 P-adenosin-diphosphate, 32 P-adenosin-monophosphate and 32 P-phosphate. Working at low temperature prevents chemical changes of the nucleotides. Extraction and thin layer chromatorgraphy turned out to be effective separation procedures for preparing samples for radioactivity measurement of the nucleotides. Autoradiographic techniques, scanning and liquid scitillation counting had been used for radioactivity measurements of the radioactive zones at the chromatograms. The results of these measurements provide information concerning the normal composition of adenosin-phosphates in the tissues of the housefly. If the animals are exposed to toxic chemicals, to insecticides, the composition of the phosphate containing compounds is changing. The concentration of adenosin-triphosphate is decreasing and the concentration of phosphate is increasing. This can be very easily shown by scanning the chromatograms of the extracts of the muscles of houseflies after feeding the animals with radioactive phosphate. Using this method, it is possible to show the toxic action of insecticides upon the metabolism of adenosin-phosphates. The decrease of the radioactivity at the zone of the adenosin-triphosphate and the increase of the radioactivity at the phosphate zone corresponds to the toxic action of foreign chemicals like insecticides. By using this tracer technique, it may be possible to investigate the toxic action of several toxic chemicals, if they are applied at the same time, thus investigating synergetic actions of environmental poisons. (Author)

Cardiotonic agent milrinone stimulates resorption in rodent bone organ culture.

OpenAIRE

Krieger, N S; Stappenbeck, T S; Stern, P H

1987-01-01

The cardiotonic agent amrinone inhibits bone resorption in vitro. Milrinone, an amrinone analog, is a more potent cardiotonic agent with lower toxicity. In contrast to amrinone, milrinone stimulated resorption in cultures of neonatal mouse calvaria and fetal rat limb bones. Threshold doses were 0.1 microM in calvaria and 0.1 mM in limb bones; maximal stimulation occurred in calvaria at 0.1 mM. Maximal responses to milrinone and parathyroid hormone were comparable. Milrinone concentrations bel...

Liver scanning with sup(99m)Tc-phytate

Energy Technology Data Exchange (ETDEWEB)

Kubo, A; Isobe, Y; Kobayashi, T; (Keio Univ., Tokyo (Japan). School of Medicine); Kinoshita, Fumio; Shibata, Masayoshi

1975-03-01

/sup 198/Au-colloid has been widely used for liver scanning in Japan but it is not the best scanning agent because of the large exposure dose to the patient. The authors performed a few basic experiments with sup(99m)Tc-phytate, the preparation of which is very easy. The labeling efficiency was found to be 97.5% immediately after preparation and it remained fairly stable for a period of time. As a result, the compound can be used up to 6 hours after preparation without fear of chemical instability. Liver scanning with sup(99m)Tc-phytate was done on 116 patients and was compared with /sup 198/Au-colloid liver-scanning. Scans made with sup(99m)Tc were found to be superior to those made with /sup 198/Au in the resolution of surface defects in the liver, while at increasing depths the resolution with sup(99m)Tc dropped rapidly, apparently due to absorption of its relatively low energy photon. This indicates the importance of taking multidirectional views. The degrees of splenic concentration of sup(99m)Tc-phytate were fairly close to those of /sup 198/Au-colloid. Therefore, liver scanning with sup(99m)Tc-phytate is useful in the diagnostic evaluation of diffuse parenchymal liver disease.

Liver scanning with sup(99m)Tc-phytate

International Nuclear Information System (INIS)

Kubo, Atsushi; Isobe, Yoshinori; Kobayashi, Takeshi; Kinoshita, Fumio; Shibata, Masayoshi.

1975-01-01

198 Au-colloid has been widely used for liver scanning in Japan but it is not the best scanning agent because of the large exposure dose to the patient. The authors performed a few basic experiments with sup(99m)Tc-phytate, the preparation of which is very easy. The labeling efficiency was found to be 97.5% immediately after preparation and it remained fairly stable for a period of time. As a result, the compound can be used up to 6 hours after preparation without fear of chemical instability. Liver scanning with sup(99m)Tc-phytate was done on 116 patients and was compared with 198 Au-colloid liver-scanning. Scans made with sup(99m)Tc were found to be superior to those made with 198 Au in the resolution of surface defects in the liver, while at increasing depths the resolution with sup(99m)Tc dropped rapidly, apparently due to absorption of its relatively low energy photon. This indicates the importance of taking multidirectional views. The degrees of splenic concentration of sup(99m)Tc-phytate were fairly close to those of 198 Au-colloid. Therefore, liver scanning with sup(99m)Tc-phytate is useful in the diagnostic evaluation of diffuse parenchymal liver disease. (auth.)

Melatonin: a protective and detoxifying agent in paraquat toxicity

International Nuclear Information System (INIS)

Ghanem, M.; Gad, H.; Hanan; Aziz, A.; Nasr, M.

2002-01-01

The ability of melatonin as a protective and detoxifying agent against paraquat-induced oxidative damage in rat lungs and liver was examined. Changes in reduced glutathione (OSH) concentration and malonaldehyde (MDA) level were measured. Pathological examination to lungs and liver was done. Paraquat in 2 doses (20,70 mg/kg) was injected I.P. into rats with melatonin (10 mg/kg) I. P. either before and after paraquat intoxication or only after it. Melatonin proved its protective role when given before and after paraquat intoxication more than its detoxifying effect when given only after paraquat. The biochemical improvement following melatonin therapy was more evident than the histopathological one. (author)

Technological advancements for the detection of and protection against biological and chemical warfare agents.

Science.gov (United States)

Eubanks, Lisa M; Dickerson, Tobin J; Janda, Kim D

2007-03-01

There is a growing need for technological advancements to combat agents of chemical and biological warfare, particularly in the context of the deliberate use of a chemical and/or biological warfare agent by a terrorist organization. In this tutorial review, we describe methods that have been developed both for the specific detection of biological and chemical warfare agents in a field setting, as well as potential therapeutic approaches for treating exposure to these toxic species. In particular, nerve agents are described as a typical chemical warfare agent, and the two potent biothreat agents, anthrax and botulinum neurotoxin, are used as illustrative examples of potent weapons for which countermeasures are urgently needed.

Gadolinium-based contrast agents in pediatric magnetic resonance imaging

Energy Technology Data Exchange (ETDEWEB)

Gale, Eric M.; Caravan, Peter [Massachusetts General Hospital, Harvard Medical School, Department of Radiology, The Martinos Center for Biomedical Imaging, Boston, MA (United States); Rao, Anil G. [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); McDonald, Robert J. [College of Medicine, Mayo Clinic, Department of Radiology, Rochester, MN (United States); Winfeld, Matthew [University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (United States); Fleck, Robert J. [Cincinnati Children' s Hospital Medical Center, Department of Pediatric Radiology, Cincinnati, OH (United States); Gee, Michael S. [MassGeneral Hospital for Children, Harvard Medical School, Division of Pediatric Imaging, Department of Radiology, Boston, MA (United States)

2017-05-15

Gadolinium-based contrast agents can increase the accuracy and expediency of an MRI examination. However the benefits of a contrast-enhanced scan must be carefully weighed against the well-documented risks associated with administration of exogenous contrast media. The purpose of this review is to discuss commercially available gadolinium-based contrast agents (GBCAs) in the context of pediatric radiology. We discuss the chemistry, regulatory status, safety and clinical applications, with particular emphasis on imaging of the blood vessels, heart, hepatobiliary tree and central nervous system. We also discuss non-GBCA MRI contrast agents that are less frequently used or not commercially available. (orig.)

Effectiveness of donepezil, rivastigmine, and (+/-)huperzine A in counteracting the acute toxicity of organophosphorus nerve agents: comparison with galantamine.

Science.gov (United States)

Aracava, Yasco; Pereira, Edna F R; Akkerman, Miriam; Adler, Michael; Albuquerque, Edson X

2009-12-01

Galantamine, a centrally acting cholinesterase (ChE) inhibitor and a nicotinic allosteric potentiating ligand used to treat Alzheimer's disease, is an effective and safe antidote against poisoning with nerve agents, including soman. Here, the effectiveness of galantamine was compared with that of the centrally active ChE inhibitors donepezil, rivastigmine, and (+/-)huperzine A as a pre- and/or post-treatment to counteract the acute toxicity of soman. In the first set of experiments, male prepubertal guinea pigs were treated intramuscularly with one of the test drugs and 30 min later challenged with 1.5 x LD(50) soman (42 microg/kg s.c.). All animals that were pretreated with galantamine (6-8 mg/kg), 3 mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (+/-)huperzine A survived the soman challenge, provided that they were also post-treated with atropine (10 mg/kg i.m.). However, only galantamine was well tolerated. In subsequent experiments, the effectiveness of specific treatment regimens using 8 mg/kg galantamine, 3 mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (+/-)huperzine A was compared in guinea pigs challenged with soman. In the absence of atropine, only galantamine worked as an effective and safe pretreatment in animals challenged with 1.0 x LD(50) soman. Galantamine was also the only drug to afford significant protection when given to guinea pigs after 1.0 x LD(50) soman. Finally, all test drugs except galantamine reduced the survival of the animals when administered 1 or 3 h after the challenge with 0.6 or 0.7 x LD(50) soman. Thus, galantamine emerges as a superior antidotal therapy against the toxicity of soman.

Near-infrared reflectance bull’s eye maculopathy as an early indication of hydroxychloroquine toxicity

Directory of Open Access Journals (Sweden)

Wong KL

2015-03-01

Full Text Available Keye L Wong,1 Scott E Pautler,2 David J Browning31Retina Associates of Sarasota, Sarasota, FL, USA; 2Retina Vitreous Associates of Florida, Tampa, FL, USA; 3Charlotte Eye Ear Nose and Throat Associates, Charlotte, NC, USAImportance: In some patients, hydroxychloroquine ocular toxicity may progress even following cessation of therapy. Any leverage the clinician may use to allow earlier detection may avert significant vision loss.Observation: We report three cases suggesting that bull’s eye maculopathy seen on near-infrared reflectance with a confocal scanning laser ophthalmoscope could be an early, objective manifestation of hydroxychloroquine ocular toxicity, and with progression of the disease this near-infrared “bull’s eye” change may disappear.Conclusion and relevance: Alerting clinicians to this observation may allow a larger case series to corroborate the hypothesis that bull’s eye maculopathy detected by near-infrared reflectance may represent an early sign of hydroxychloroquine toxicity.Keywords: confocal, scanning laser ophthalmoscope, multifocal ERG

[Can nitrates lead to indirect toxicity?].

Science.gov (United States)

Hamon, M

2007-09-01

For many years, nitrates have been used, at low dosages, as an additive in salted food. New laws have been promulgated to limit their concentration in water due to increased levels found in soils, rivers and even the aquifer. Although nitrate ions themselves have not toxic properties, bacterial reduction into nitrite ions (occurring even in aqueous medium) can lead to nitrous anhydride, which in turn generates nitrosonium ions. Nitrosium ions react with secondary amine to give nitrosamines, many of which are cancer-inducing agents at very low doses. Opinions on this toxicity are clear-cut and difficult to reconcile. In fact, increased levels are due, in a large part, to the use of nitrates as fertiliéers but also to bacterial transformation of human and animal nitrogenous wastes such as urea.

Acute toxicity from baking soda ingestion.

Science.gov (United States)

Thomas, S H; Stone, C K

1994-01-01

Sodium bicarbonate is an extremely well-known agent that historically has been used for a variety of medical conditions. Despite the widespread use of oral bicarbonate, little documented toxicity has occurred, and the emergency medicine literature contains no reports of toxicity caused by the ingestion of baking soda. Risks of acute and chronic oral bicarbonate ingestion include metabolic alkalosis, hypernatremia, hypertension, gastric rupture, hyporeninemia, hypokalemia, hypochloremia, intravascular volume depletion, and urinary alkalinization. Abrupt cessation of chronic excessive bicarbonate ingestion may result in hyperkalemia, hypoaldosteronism, volume contraction, and disruption of calcium and phosphorus metabolism. The case of a patient with three hospital admissions in 4 months, all the result of excessive oral intake of bicarbonate for symptomatic relief of dyspepsia is reported. Evaluation and treatment of patients with acute bicarbonate ingestion is discussed.

Development of novel alkylating drugs as anticancer agents.

Science.gov (United States)

Izbicka, Elzbieta; Tolcher, Anthony W

2004-06-01

Although conventional alkylating drugs have proven efficacy in the treatment of malignancies, the agents themselves are not selective. Therefore, non-specific alkylation of cellular nucleophilic targets may contribute to many of the observed toxic effects. Novel approaches to drug discovery have resulted in candidate agents that are focused on 'soft alkylation'--alkylators with greater target selectivity. This review highlights the discovery of small molecule drugs that bind to DNA with higher selectivity, act in a unique hypoxic tumor environment, or covalently bind specific protein targets overexpressed in cancer, such as topoisomerase II, glutathione transferase pi1, beta-tubulin and histone deacetylase.

Balancing repair and tolerance of DNA damage caused by alkylating agents.

Science.gov (United States)

Fu, Dragony; Calvo, Jennifer A; Samson, Leona D

2012-01-12

Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for a favourable response of an organism to alkylating agents. Furthermore, the response of an individual to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity.

Fluorine-Containing Taxoid Anticancer Agents and Their Tumor-Targeted Drug Delivery

OpenAIRE

Seitz, Joshua; Vineberg, Jacob G.; Zuniga, Edison S.; Ojima, Iwao

2013-01-01

A long-standing problem of conventional chemotherapy is the lack of tumor-specific treatments. Traditional chemotherapy relies on the premise that rapidly proliferating cancer cells are more likely to be killed by a cytotoxic agent. In reality, however, cytotoxic agents have very little or no specificity, which leads to systemic toxicity, causing undesirable severe side effects. Consequently, various “molecularly targeted cancer therapies” have been developed for use in specific cancers, incl...

Technetium-Iron Complex. Radiopharmaceutical for Renal Scanning and Function Studies

Energy Technology Data Exchange (ETDEWEB)

Aquino, J. A.; Cunningham, R. M. [Victoria General Hospital and Dalhousie Medical School, Halifax, NS (Canada)

1969-05-15

A preliminary report on the use of a technetium-iron complex as a radiopharmaceutical in the evaluation of kidney function as well as renal scanning is presented. The first part considers the {sup 99m}Tc iron complex as an agent to determine the kidney function. This is correlated with the conventional {sup 131}I Hippuran renogram as well as the mercury accumulative test. The second part describes the use of the {sup 99m}Tc iron complex as a renal scanning agent; again it is compared with {sup 197}Hg Neohydrin. The availability of the Anger gamma camera, along with {sup 99m}Tc and its favourable characteristics have encouraged further search for better preparations. Among these is the {sup 99m}Tc iron complex. The authors' technique of preparation is described. Although the pertechnetate ion is not very active chemically in combining with other compounds, it is readily reduced to more reactive lower valence states. Such alterations of chemical form produce changes in biologic localization of {sup 99m}Tc. After the intravenous injection of {sup 99m}Tc as pertechnetate, it is rapidly localized in the stomach, urinary bladder, thyroid, and salivary glands. Excretion during the first 24 h occurs largely through the urine. Harper et al. have shown that the {sup 99m}Tc iron complex is rapidly excreted through the urine. The initial disappearance from the plasma is so very rapid that 50% or more has usually left the blood in 3-5 min. Part of the 5'irnTc is fixed in the kidney which constitutes half of what is retained in the body. Our technique consists of obtaining the conventional {sup 131}I Hippuran renogram. This is followed by the injection of {sup 99m}Tc iron complex. The two renograms obtained, using the two agents, are correlated along with other diagnostic tests. Since the {sup 99m}Tc iron complex used for doing the renogram can be used in scanning the kidney, both kidneys are scanned using the Anger gamma camera. Comparative scans are done with the use of {sup

Inflammation Scan Using {sup 99m}Tc-HMPAO Labelled Leukocytes

Energy Technology Data Exchange (ETDEWEB)

Yang, Woo Jin; Chung, Soo Kyo; Shinn, Kyung Sub; Bahk, Yong Whee; Kim, Hoon Kyo [Catholic University College of Medicine, Seoul (Korea, Republic of)

1989-07-15

Inflammation scan using radiolabelled leukocytes has high sensitivity and specificity. Several methods for labelling leukocytes have been evaluated using P-32 diisopropyl fluorophosphate (DFP -32), H-3 thymidine, Cr-51 chromate, Ga-67 citrate and {sup 99m}Tc-sulfur colloid. In-111-oxine has proved so far to be the most reliable agent for labelling leukocytes. In-111-oxine is, however, expensive, not easily available when needed, and its radiation dose to leukocytes is relatively high. Moreover, resolution of the resultant image is relatively poor. {sup 99m}Tc is still the agent of choice because of, as compared with the indium, its favorable physical characteristics, lower cost and availability. Now the technique for labelling the leukocytes with technetium is successfully obtained using the lipophilic HMPAO with higher efficiency for granulocytes than for other cells. With this technique it is possible to label leukocytes in plans to improve the viability of the leukocytes. Inflammation scan using {sup 99m}Tc-HMPAO has been evaluated in several laboratories, and difference in methods for separation and labelling accounts for difference in efficiency, viability and biodistribution of the labelled leukocytes. We performed inflammation scan using leukocytes labelled with {sup 99m}Tc-HMPAO in three dogs 24 hours after inoculation of live E. Coli and S. Aureus in their right abdominal wall. We separated mixed leukocytes by simple sedimentation using 6% hetastarch (HES) and labelled the leukocytes with {sup 99m}Tc-HMPAO in 20% cell free plasma diluted with phosphate buffer solution. Uptake was high in the liver and spleen but is was minimal in the lungs on whole body scan. Kidneys and intestine showed minimal activity although it was high in the urinary bladder. Uptake of labelled leukocytes in the inflammation site was definite on 2 hour-postinjection scan and abscess was clearly delineated on 24 hour-delayed scan with high target-to-nontarget ratio. 4). Inflammation

TU-F-12A-09: GLCM Texture Analysis for Normal-Tissue Toxicity: A Prospective Ultrasound Study of Acute Toxicity in Breast-Cancer Radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Liu, T; Yang, X; Curran, W; Torres, M [Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA (United States)

2014-06-15

Purpose: To evaluate the morphologic and structural integrity of the breast glands using sonographic textural analysis, and identify potential early imaging signatures for radiation toxicity following breast-cancer radiotherapy (RT). Methods: Thirty-eight patients receiving breast RT participated in a prospective ultrasound imaging study. Each participant received 3 ultrasound scans: 1 week before RT (baseline), and at 6-week and 3-month follow-ups. Patients were imaged with a 10-MHz ultrasound on the four quadrant of the breast. A second order statistical method of texture analysis, called gray level co-occurrence matrix (GLCM), was employed to assess RT-induced breast-tissue toxicity. The region of interest (ROI) was 28 mm × 10 mm in size at a 10 mm depth under the skin. Twenty GLCM sonographic features, ratios of the irradiated breast and the contralateral breast, were used to quantify breast-tissue toxicity. Clinical assessment of acute toxicity was conducted using the RTOG toxicity scheme. Results: Ninety-seven ultrasound studies (776 images) were analyzed; and 5 out of 20 sonographic features showed significant differences (p < 0.05) among the baseline scans, the acute toxicity grade 1 and 2 groups. These sonographic features quantified the degree of tissue damage through homogeneity, heterogeneity, randomness, and symmetry. Energy ratio value decreased from 108±0.05 (normal) to 0.99±0.05 (Grade 1) and 0.84±0.04 (Grade 2); Entropy ratio value increased from 1.01±0.01 to 1.02±0.01 and 1.04±0.01; Contrast ratio value increased from 1.03±0.03 to 1.07±0.06 and 1.21±0.09; Variance ratio value increased from 1.06±0.03 to 1.20±0.04 and 1.42±0.10; Cluster Prominence ratio value increased from 0.98±0.02 to 1.01±0.04 and 1.25±0.07. Conclusion: This work has demonstrated that the sonographic features may serve as imaging signatures to assess radiation-induced normal tissue damage. While these findings need to be validated in a larger cohort, they suggest

Using cheminformatics to find simulants for chemical warfare agents

Energy Technology Data Exchange (ETDEWEB)

Lavoie, J.; Srinivasan, Sree [Molecular Sciences and Engineering Team, U.S. Army Natick Soldier Research, Development and Engineering Center, 15 Kansas Street, Natick, MA 01760 (United States); Nagarajan, R., E-mail: Ramanathan.Nagarajan@us.army.mil [Molecular Sciences and Engineering Team, U.S. Army Natick Soldier Research, Development and Engineering Center, 15 Kansas Street, Natick, MA 01760 (United States)

2011-10-30

Highlights: {yields} Summary of chemical warfare agent (CWA) simulants in current use. {yields} Application of method of molecular similarity to CWA and simulants. {yields} Quantitative metric for CWA-simulant similarity. {yields} Rank ordering of simulants in current use. {yields} Potential of method to identify simulants for emerging agents. - Abstract: Direct experimentation with chemical warfare agents (CWA) to study important problems such as their permeation across protective barrier materials, decontamination of equipment and facilities, or the environmental transport and fate of CWAs is not feasible because of the obvious toxicity of the CWAs and associated restrictions on their laboratory use. The common practice is to use 'simulants,' namely, analogous chemicals that closely resemble the CWAs but are less toxic, with the expectation that the results attained for simulants can be correlated to how the CWAs would perform. Simulants have been traditionally chosen by experts, by means of intuition, using similarity in one or more physical properties (such as vapor pressure or aqueous solubility) or in the molecular structural features (such as functional groups) between the stimulant and the CWA. This work is designed to automate the simulant identification process backed by quantitative metrics, by means of chemical similarity search software routinely used in pharmaceutical drug discovery. The question addressed here is: By the metrics of such software, how similar are traditional simulants to CWAs? That is, what is the numerical 'distance' between each CWA and its customary simulants in the quantitative space of molecular descriptors? The answers show promise for finding close but less toxic simulants for the ever-increasing numbers of CWAs objectively and fast.

Using cheminformatics to find simulants for chemical warfare agents

International Nuclear Information System (INIS)

Lavoie, J.; Srinivasan, Sree; Nagarajan, R.

2011-01-01

Highlights: → Summary of chemical warfare agent (CWA) simulants in current use. → Application of method of molecular similarity to CWA and simulants. → Quantitative metric for CWA-simulant similarity. → Rank ordering of simulants in current use. → Potential of method to identify simulants for emerging agents. - Abstract: Direct experimentation with chemical warfare agents (CWA) to study important problems such as their permeation across protective barrier materials, decontamination of equipment and facilities, or the environmental transport and fate of CWAs is not feasible because of the obvious toxicity of the CWAs and associated restrictions on their laboratory use. The common practice is to use 'simulants,' namely, analogous chemicals that closely resemble the CWAs but are less toxic, with the expectation that the results attained for simulants can be correlated to how the CWAs would perform. Simulants have been traditionally chosen by experts, by means of intuition, using similarity in one or more physical properties (such as vapor pressure or aqueous solubility) or in the molecular structural features (such as functional groups) between the stimulant and the CWA. This work is designed to automate the simulant identification process backed by quantitative metrics, by means of chemical similarity search software routinely used in pharmaceutical drug discovery. The question addressed here is: By the metrics of such software, how similar are traditional simulants to CWAs? That is, what is the numerical 'distance' between each CWA and its customary simulants in the quantitative space of molecular descriptors? The answers show promise for finding close but less toxic simulants for the ever-increasing numbers of CWAs objectively and fast.

Evaluation of the biological and scanning distribution of hydroxyapatite-153Sm radiotherapeutic agent

International Nuclear Information System (INIS)

Herrera, J.; Paredes, N.; Portilla, A.; Miranda, J.; Carrillo, D.

1999-01-01

Fixation of 153 Sm labeled hydroxyapatite (HA) in the synovial capsule and extra articular localization were evaluated by means of biological distribution tests and gamma scanning studies. These were carried out using HA- 153 Sm with particle size ranging between 5 and μm, and radiochemical purity above 99%. Animal models used were wistar rats and new zealand rabbits. Rabbits were injected with 7,4 MBq of HA- 153 Sm while rats received between 1,85 and 92,6 MBq of HA- 153 Sm. In both cases injection was given in the intra articular area. After injection, scanning images were obtained in rabbits on the 1 st , 3 rd and 7 st day and in rats on the 2 nd and 7 th day. Biological distribution studies are conducted in the 2 hours to 9 days range in rats and one the 7 th day in rabbits. No extra articular localization of HA- 153 Sm was found in scanning conducted on rabbits by the 1 st , 3 rd and 7 st day after injection, neither on rats by the 2 nd and 7 th day. Biological distributions for rabbits and rats show localization above 99% in the intra articular area, during the evaluated periods of time. The evaluations of the biological distribution and the scintigraphic images show that fixation of HA- 153 Sm in the synovial capsule up to the 9 th day is very high

Interaction of chelating agents with cadmium in mice and rats.

Science.gov (United States)

Eybl, V; Sýkora, J; Koutenský, J; Caisová, D; Schwartz, A; Mertl, F

1984-01-01

The influence of several chelating agents (CaDTPA, ZnDTPA, CaEDTA, ZnEDTA, DMSA, D-penicillamine and DMPS, DMP and DDC) on the acute toxicity of CdCl2 and on the whole body retention and tissue distribution of cadmium after the IV application of 115mCdCl2 was compared in mice. The chelating agents were applied immediately after the application of cadmium. CaDTPA, ZnDTPA and DMSA appeared to be the most effective antidotes. However, DMSA increased the amount of cadmium retained in kidneys. The treatment of cadmium-poisoned mice with the combination of DMSA (IP) and ZnDTPA (SC) (all the compounds were injected in equimolar dose) decreased the toxicity of cadmium more than treatment with one chelating agents (given in a 2:1 dose). However, by studying the effect of these chelating agents and their combination of the retention and distribution of Cd in mice, it was demonstrated that the combined application of the antidotes showed little or no improvement over the results obtained with the most effective of the individual components. In the urine of rats injected with CdCl2 and treated with the chelating agents (CaDTPA, ZnDTPA, DMSA), the presence of cadmium complexes was demonstrated. The formation of mixed ligand chelates in vivo was not proved. Experiments in mice given a single injection of 115mCd-labeled Cd complexes of DMPS, DMSA and DTPA showed a high retention of cadmium in the organisms after the IV application of CdDMPS and CdDMSA complexes. PMID:6734561

Protection by thiols against poisoning by radiomimetic agents. Chapter 8

International Nuclear Information System (INIS)

Bacq, Z.M.

1975-01-01

A review is presented of reports of studies aimed at detecting a protective effect of thiols against radiomimetic alkylating agents such as those used in cancer therapy (nitrogen mustards (HN2), sarcolysine, busulfan, etc.). Protection by thiols against alkylating agents has been observed in mammals, plant cells, bacteria, isolated mammalian cells and in model systems. The lack of correlation between the protective power of various thiols against radiomimetic agents and ionizing radiations indicates that different mechanisms are involved. Studies have been made of the toxicity of the protector and the competition factor, increased excretion of detoxication products of alkylating agents, decreased alkylation of DNA and RNA both in vivo and in vitro, the protection of hematopoietic tissues, tumours and the adrenal cortex, and the modification of the effects of nitrosoalkylamines, carbon tetrachloride and fungistatics by thiols. The restriction of DNA alkylation by the competitive removal of radiomimetic agents is thought to account for the protective effect of thiols against radiomimetic agents. (U.K.)

The use of contrast agents in cardiac MRI

International Nuclear Information System (INIS)

Maurer, A.H.; Osbakken, M.

1988-01-01

Inherent NMR phenomena such as T/sub 1/ and T/sub 2/, and proton density can be used to provide tissue contrast on MR images. However, there are times when this contrast is not sufficient or does not provide tissue characterization data sufficient for use in definition of a pathophysiological insult. In this later case, paramagnetic agents might be of use in enhancement of relaxation time differences in one tissue or one portion of a tissue compared to another. Although several agents have been evaluated in this regard, most have been found inadequate because of their tissue toxicity. At present, gadolinium diethylenetriamine pentaacetric acid (Gd-DTPA) (which is an agent used in nuclear medicine studies) appears to be a good agent to use to distinguish normal from ischemic tissue. This agent has been used by a number of investigators to evaluate myocardial ischemia and provides images with better sensitivity and specificity for ischemia than imaging techniques using natural tissue contrast based on T/sub 1/ and T/sub 2/ differences

A general mechanism for intracellular toxicity of metal-containing nanoparticles

KAUST Repository

Sabella, Stefania

2014-04-09

The assessment of the risks exerted by nanoparticles is a key challenge for academic, industrial, and regulatory communities worldwide. Experimental evidence points towards significant toxicity for a range of nanoparticles both in vitro and in vivo. Worldwide efforts aim at uncovering the underlying mechanisms for this toxicity. Here, we show that the intracellular ion release elicited by the acidic conditions of the lysosomal cellular compartment-where particles are abundantly internalized-is responsible for the cascading events associated with nanoparticles-induced intracellular toxicity. We call this mechanism a "lysosome-enhanced Trojan horse effect" since, in the case of nanoparticles, the protective cellular machinery designed to degrade foreign objects is actually responsible for their toxicity. To test our hypothesis, we compare the toxicity of similar gold particles whose main difference is in the internalization pathways. We show that particles known to pass directly through cell membranes become more toxic when modified so as to be mostly internalized by endocytosis. Furthermore, using experiments with chelating and lysosomotropic agents, we found that the toxicity mechanism for different metal containing NPs (such as metallic, metal oxide, and semiconductor NPs) is mainly associated with the release of the corresponding toxic ions. Finally, we show that particles unable to release toxic ions (such as stably coated NPs, or diamond and silica NPs) are not harmful to intracellular environments. The Royal Society of Chemistry 2014.

A general mechanism for intracellular toxicity of metal-containing nanoparticles

KAUST Repository

Sabella, Stefania; Carney, Randy P.; Brunetti, Virgilio; Malvindi, Maria Ada; Al-Juffali, Noura; Vecchio, Giuseppe; Janes, Sam M.; Bakr, Osman; Cingolani, Roberto; Stellacci, Francesco; Pompa, Pier Paolo

2014-01-01

The assessment of the risks exerted by nanoparticles is a key challenge for academic, industrial, and regulatory communities worldwide. Experimental evidence points towards significant toxicity for a range of nanoparticles both in vitro and in vivo. Worldwide efforts aim at uncovering the underlying mechanisms for this toxicity. Here, we show that the intracellular ion release elicited by the acidic conditions of the lysosomal cellular compartment-where particles are abundantly internalized-is responsible for the cascading events associated with nanoparticles-induced intracellular toxicity. We call this mechanism a "lysosome-enhanced Trojan horse effect" since, in the case of nanoparticles, the protective cellular machinery designed to degrade foreign objects is actually responsible for their toxicity. To test our hypothesis, we compare the toxicity of similar gold particles whose main difference is in the internalization pathways. We show that particles known to pass directly through cell membranes become more toxic when modified so as to be mostly internalized by endocytosis. Furthermore, using experiments with chelating and lysosomotropic agents, we found that the toxicity mechanism for different metal containing NPs (such as metallic, metal oxide, and semiconductor NPs) is mainly associated with the release of the corresponding toxic ions. Finally, we show that particles unable to release toxic ions (such as stably coated NPs, or diamond and silica NPs) are not harmful to intracellular environments. The Royal Society of Chemistry 2014.

Evaluation of the toxic effect of endocrine disruptor Bisphenol A (BPA) in the acute and chronic toxicity tests with Pomacea lineata gastropod.

Science.gov (United States)

de Andrade, André Lucas Correa; Soares, Priscila Rafaela Leão; da Silva, Stephannie Caroline Barros Lucas; da Silva, Marília Cordeiro Galvão; Santos, Thamiris Pinheiro; Cadena, Marilia Ribeiro Sales; Soares, Pierre Castro; Cadena, Pabyton Gonçalves

2017-07-01

Bisphenol A (BPA) is a plasticizer and a risk when it interacts with organisms, and can cause changes in the development and reproduction of them. This study aimed to evaluate the effects of BPA, by acute and chronic toxicity tests with neonates and adults of Pomacea lineata. Adults and neonates were divided into groups exposed to BPA (1-20mg/L), or 17β-estradiol (1mg/L) and control in the acute and chronic toxicity tests. Behavior, heart rate, reproduction and hemolymph biochemical analysis were measured. In the acute toxicity test, the 96-h LC 50 with adults was 11.09 and with neonates was 3.14mg/L. In this test, it was observed lethargic behavior and an increase of 77.6% of aspartate aminotransferase in the adults' hemolymph (ptest, it was observed behaviors associated with reproduction, as Copulate, in the groups exposed to BPA. The results that were found in this study proved that BPA is a potentially toxic agent to Pomacea lineata according to biological parameters evaluated. These data contribute to the understanding of BPA toxic effects' in the aquatic invertebrates. Copyright © 2017 Elsevier Inc. All rights reserved.

Studies on polyaspartamide gadolinium complexes as potential magnetic resonance imaging contrast agents

International Nuclear Information System (INIS)

Yan Guoping; Liu Maili; Li Liyun

2005-01-01

Purpose: A series of polyaspartamide gadolinium complexes containing pyridoxamine groups were studied as the potential magnetic resonance imaging (MRI) contrast agents for liver enhancement. Methods: These polyaspartamide gadolinium complexes were prepared and evaluated by relaxivity, acute toxicity studies and magnetic resonance imaging of the liver in rats. Results: These polyaspartamide gadolinium complexes have higher relaxation effectiveness than that of the clinically used gadolinium diethylenetriaminepentaacetic acid and possess the low intravenous acute toxicities to Institute for Cancer Research (ICR) mice. Magnetic resonance imaging of the liver in rats indicated that they greatly enhance the contrast of magnetic resonance images and provide prolonged intravascular duration in the liver. Conclusion: These results indicated that the polyaspartamide gadolinium complexes containing pyridoxamine groups could be considered as the appropriate MRI contrast agents for liver enhancement

Prevention of ocular toxicity by the intra-carotid perfusion of anticancer agents in the treatment of malignant glioma. Usefulness of a remodeled epidural catheter and selective CT enhancements

Energy Technology Data Exchange (ETDEWEB)

Uemura, Shozaburo; Matsukado, Yasuhiko; Yoshioka, Susumu; Ohtsuka, Tadahiro; Kuratsu, Jun-ichi; Sonoda, Hiroshi

1986-06-01

It is a problem of great concern to prevent ocular toxicity from complicating intra-carotid administration of lipophil anticancer agents. Attempts to prevent such a side effect were made during intra-carotid chemotherapy using remodeled catheter tips for epidural anesthesia. Twenty nine patients with malignant glioma received intra-carotid administration of neocarzinostatin (NCS). Six out of 17 patients (35.3 %) who received intra-carotid perfusion through an original catheter without a remodeled tip, developed ocular toxicity. The catheter tip remained proximal to the ophthalmic artery in all cases. On the other hand, 12 patients with a remodeled catheter tip did not develop ocular toxicity. In the latter group the tip of the catheter was located in the internal carotid artery sufficiently distal to the ophthalmic artery, or beyond the carotid bifurcation in 3 cases. Another advantage of the remodeled catheter was that the intra-carotid perfusion was feasible for a longer period with higher doses of NCS, than treatment with the commercial catheter for superselective embolization, which was found to be easily occluded and often ejected out of the carotid artery. Prior to and during the intra-carotid perfusion selective injection of Angiografin was performed through the catheter and the tumor was enhanced in the area of arterial supply, indicating the extent of chemotherapy and the degree of destruction of the blood-brain barrier.

Crataegus Monogyna Aqueous Extract Ameliorates Cyclophosphamide-Induced Toxicity in Rat Testis: Stereological Evidences

Directory of Open Access Journals (Sweden)

Hassan Malekinejad

2012-01-01

Full Text Available Cyclophosphamide (CP is extensively used as an antineoplastic agent for the treatment of various cancers, as well as an immunosuppressive agent. However, despite its wide spectrum of clinical uses, CP is known to cause several adverse effects including reproductive toxicity. Crataegus monogyna is one of the oldest pharmaceutical plants that have been shown to be cytoprotective by scavenging free radicals. The present study was conducted to assess whether Crataegus monogyna fruits aqueous extract with anti-oxidant properties, could serve as a protective agent against reproductive toxicity during CP treatment in a rat model. Male Wistar rats were categorized into four groups. Two groups of rats were administered CP at a dose of 5 mg in 5 ml saline/kg/day for 28 days by oral gavages. One of these groups received Crataegus monogyna aqueous extract at a dose of 20 mg/kg/day orally four hours after cyclophosphamide administration. A vehicle treated control group and a Crataegus monogyna control group were also included. The CP-treated group showed significant decreases in the body, testes and epididymides weights as well as many histological alterations. Stereological parameters and spermatogenic activities (Sertoli cell, repopulation and miotic indices were also significantly decreased by CP treatment. Notably, Crataegus coadministration caused a partial recovery in above-mentined parameters. These findings indicate that Crataegus monogyna may be partially protective against CP-induced testicular toxicity.

Production of chelating agents by Pseudomonas aeruginosa grown in the presence of thorium and uranium

International Nuclear Information System (INIS)

Premuzic, E.T.; Lin, M.; Francis, A.J.; Schubert, J.

1986-01-01

Chelating agents produced by microorganisms enhance the dissolution of iron increasing the mobility and bioavailability of the metal. Since some similarities exist in the biological behavior of ferric, thorium and uranyl ions, microorganisms resistant to these metals and which grow in their presence may produce sequestering agents of Th and U, and other metals in a manner similar to the complexation of iron by siderophores. The ability of P. aeruginosa to elaborate sequestering agents in medium containing thorium or uranium salts was tested. Uranium has a stronger inhibitory effect on growth of the organism than thorium at similar concentrations. Analyses of the culture media have shown, that relative to the control, and under the experimental conditions used, the microorganisms have produced several new chelating agents for thorium and uranium. Extracts containing these chelating agents have been tested for their decorporation potential. In vitro mouse liver bioassay and in vivo mouse toxicity tests indicate that their efficiency is comparable to DTPA and DFOA and that they are virtually non-toxic to mice. The bacterially produced compounds resemble, but are not identical to the known iron chelating siderophores isolated from microorganisms. Some of their chemical properties are also discussed. (author)

Toxicity after reirradiation of pulmonary tumours with stereotactic body radiotherapy

International Nuclear Information System (INIS)

Peulen, Heike; Karlsson, Kristin; Lindberg, Karin; Tullgren, Owe; Baumann, Pia; Lax, Ingmar; Lewensohn, Rolf; Wersäll, Peter

2011-01-01

Purpose: To assess toxicity and feasibility of reirradiation with stereotactic body radiotherapy (SBRT) after prior lung SBRT for primary lung cancer or lung metastases. Patients and materials: Twenty-nine patients reirradiated with SBRT on 32 lung lesions (11 central, 21 peripheral) were retrospectively reviewed. Median follow-up time was 12 months (range 1–97). The primary endpoint was toxicity, secondary endpoints were local control and overall survival time. Toxicity was scored according to the NCI-CTCAE version 3. Results: Grade 3–4 toxicity was scored 14 times in eight patients. Three patients died because of massive bleeding (grade 5). Larger clinical target volumes (CTV) and central tumour localization were associated with more severe toxicity. There was no correlation between mean lung dose (MLD) and lung toxicity. Local control at 5 months after reirradiation was 52%, as assessed by CT-scan (n = 12) or X-thorax (n = 3). A larger CTV was associated with poorer local control. Kaplan–Meier estimated 1- and 2-year survival rates were 59% and 43%, respectively. Conclusions: Reirradiation with SBRT is feasible although increased risk of toxicity was reported in centrally located tumours. Further research is warranted for more accurate selection of patients suitable for reirradiation with SBRT.

Toxicity and antinociceptive effects of Hamelia patens

Directory of Open Access Journals (Sweden)

Angel Josabad Alonso-Castro

Full Text Available Abstract Many medicinal herbs are used in folk medicine without taking into account their toxicity. Hamelia patens Jacq. (Rubiaceae, a Mexican endemic species, is used for the empirical treatment of pain. The aim of this work was to evaluate the toxicity and antinociceptive effects of ethanolic extracts of H. patens leaves. The toxicity of H. patens leaves (500–5000 mg/kg was evaluated in acute (14 days and subacute (28 days assays. In the subacute assay, a blood analysis (both hematology and chemistry was carried out. The antinociceptive effects of H. patens leaves (50–200 mg/kg were evaluated using thermal-induced nociception (hot plate and the chemical-induced nociceptive tests (acid acetic and formalin. In the acute toxicity test, the LD50 estimated for H. patens leaves was 2964 mg/kg i.p. and >5000 mg/kg p.o., whereas in the subacute test HPE did not affect hematological or biochemical parameters. In chemical-induced nociception models, H. patens (100 and 200 mg/kg p.o. showed antinociceptive effects with similar activity than 100 mg/kg naproxen. In the hot plate test, HPE at 100 mg/kg (17% and 200 mg/kg (25% showed moderate antinociceptive effects. HPE could be a good source of antinociceptive agents because of its good activity and low toxicity.

Acoustically active lipospheres containing paclitaxel: a new therapeutic ultrasound contrast agent.

Science.gov (United States)

Unger, E C; McCreery, T P; Sweitzer, R H; Caldwell, V E; Wu, Y

1998-12-01

Paclitaxel-carrying lipospheres (MRX-552) were developed and evaluated as a new ultrasound contrast agent for chemotherapeutic drug delivery. Paclitaxel was suspended in soybean oil and added to an aqueous suspension of phospholipids in vials. The headspace of the vials was replaced with perfluorobutane gas; the vials were sealed, and they were agitated at 4200 rpm on a shaking device. The resulting lipospheres containing paclitaxel were studied for concentration, size, acute toxicity in mice, and acoustic activity and drug release with ultrasound. Lipospheres containing sudan black dye were produced to demonstrate the acoustically active liposphere (AAL)-ultrasound release concept. Acoustically active lipospheres containing paclitaxel had a mean particle count of approximately 1 x 10(9) particles per mL and a mean size of 2.9 microns. Acute toxicity studies in mice showed a 10-fold reduction in toxicity for paclitaxel in AALs compared with free paclitaxel. The AALs reflected ultrasound as a contrast agent. Increasing amounts of ultrasound energy selectively ruptured the AALs and released the paclitaxel. Acoustically active lipospheres represent a new class of acoustically active drug delivery vehicles. Future studies will assess efficacy of AALs for ultrasound-mediated drug delivery.

Inter-individual susceptibility to environmental toxicants-A current assessment

International Nuclear Information System (INIS)

Nebert, Daniel W.

2005-01-01

Virtually all diseases have an environmental component. The two most important factors affecting your unique risk of an environmental disease (toxicity or cancer) are (a) your exposure to the environmental agent and (b) your genes. Epidemiologists have found ways to calculate inter-individual risk-if the exposure to environmental agents is sufficiently high and can be documented (e.g., years of cigarette smoking, taking prescribed drugs, drinking alcohol, or exposure to radon or other radioactive material, etc.). If the dose of environmental agents is lower and more ambiguous (e.g., exposure to chemicals on the job, herbicides sprayed on a golf course, outdoor or indoor air pollution, endocrine disruptors in cans of food, living near a toxic waste dump site, etc.), however, calculations of inter-individual risk become much more difficult. Highly accurate DNA tests for genetic susceptibility to toxicity and cancer have been sought in order to identify individuals at increased risk; this type of research represents the leading edge of phenotype-genotype association studies and is the major goal of most public health and preventive medicine programs. The task, however, has turned out to be far more challenging than anticipated. The major stumbling block has been the difficulty in determining an unequivocal phenotype or an unequivocal genotype. We were quite optimistic 5-10 years ago that this would be easy, but now we are beginning to appreciate how difficult it is to determine an unequivocal phenotype or genotype with certainty. For many reasons set forth in this overview, it appears that DNA testing alone, to predict and prevent environmental disease on an individual basis, may be virtually impossible with current knowledge and technologies and will require novel insights before major practical applications will evolve

Toxicity of carbon nanotubes to the activated sludge process

International Nuclear Information System (INIS)

Luongo, Lauren A.; Zhang Xiaoqi

2010-01-01

The discharge of carbon nanotubes (CNTs) from industrial waste or disposal of such materials from commercial and/or domestic use will inevitably occur with increasing production and enter into wastewater treatment facilities with unknown consequences. Therefore, a better knowledge of the toxicity of CNTs to biological processes in wastewater treatment will be critical. This study examined the toxicity of multi-walled carbon nanotubes (MWCNTs) on the microbial communities in activated sludge. A comparative study using the activated sludge respiration inhibition test was performed on both unsheared mixed liquor and sheared mixed liquor to demonstrate the potential toxicity posed by MWCNTs and to illustrate the extent of extracellular polymeric substances (EPS) in protecting the microorganisms from the toxicity of CNTs. Respiration inhibition was observed for both unsheared and sheared mixed liquor when MWCNTs were present, however, greater respiration inhibition was observed for the sheared mixed liquor. The toxicity observed by the respiration inhibition test was determined to be dose-dependent; the highest concentration of MWCNTs exhibited the highest respiration inhibition. Scanning Electron Microscopy (SEM) images demonstrated direct physical contact between MWCNTs and activated sludge flocs.

Retinal toxicity associated with chronic exposure to hydroxychloroquine and its ocular screening. Review.

Science.gov (United States)

Geamănu Pancă, A; Popa-Cherecheanu, A; Marinescu, B; Geamănu, C D; Voinea, L M

2014-09-15

Hydroxychloroquine sulfate (HCQ, Plaquenil) is an analogue of chloroquine (CQ), an antimalarial agent, used for the treatment of systemic lupus erythematosus, rheumatoid arthritis and other autoimmune disorders. Its use has been associated with severe retinal toxicity, requiring a discontinuation of therapy. Because it presents potential secondary effects including irreversible maculopathy, knowledge of incidence, risk factors, drug toxicity and protocol screening of the patients it represents important data for the ophthalmologists. Thus, it is imperative that rheumatologists, medical internists and ophthalmologists are aware of the toxicity from hydroxychloroquine they should also be careful to minimize its occurrence and effects.

Algorithm of Molecular and Biological Assessment of the Mechanisms of Sensitivity to Drug Toxicity by the Example of Cyclophosphamide.

Science.gov (United States)

Telegin, L Yu; Sarmanaev, S Kh; Devichenskii, V M; Tutelyan, V A

2018-01-01

Comparative study of the liver, blood, and spleen of DBA/2JSto and BALB/cJLacSto mice sensitive and resistant to acute toxicity of the cyclophosphamide allowed us to reveal basic toxicity biomarkers of this antitumor and immunosuppressive agent. Obtained results can be used for the development of an algorithm for evaluation of toxic effects of drugs and food components.

Structural, spectroscopic and biological investigation of copper oxides nanoparticles with various capping agents

Energy Technology Data Exchange (ETDEWEB)

Nowak, A., E-mail: ana.maria.nowak@gmail.com [A. Chelkowski Institute of Physics, University of Silesia, Katowice (Poland); Szade, J.; Talik, E.; Ratuszna, A. [A. Chelkowski Institute of Physics, University of Silesia, Katowice (Poland); Ostafin, M. [Agricultural University of Cracow, Department of Microbiology, Krakow (Poland); Peszke, J. [A. Chelkowski Institute of Physics, University of Silesia, Katowice (Poland)

2014-06-01

Powder composed of copper oxides nanoparticles with various capping agents has been synthesized and characterized with the use of X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and X-ray diffraction (XRD). Polyvinyl alcohol (PVA), glycol propylene, glycerin and glycerin plus ammonia were used as capping agents. The scanning electron microscopy (SEM) studies showed that nanoparticles form agglomerates with the size from 80 to 120 nm while particles size determined from the XRD experiment was in the range from 7 to 21 nm. XPS and XRD experiments revealed that depending on capping and reducing agents used in the synthesis nanoparticles are composed of Cu{sub 2}O, CuO or a mixture of them. The biological activity test performed for a selected sample where the capping agent was glycerin plus ammonia has shown promising killing/inhibiting behavior, very effective especially for Gram negatives bacteria. - Highlights: • We obtained copper oxide nanoparticles in a powder form. • Several capping agents were tested. • Structural and chemical tests showed that the main component were Cu{sub 2}O and CuO. • The size of nanoparticles was in the range 7–21 nm. • Nanoparticles with glycerin and ammonia capping agent showed good antibacterial properties.

First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer

Directory of Open Access Journals (Sweden)

Shu Yong-Qian

2010-09-01

Full Text Available Abstract Background Lung cancer is a malignant carcinoma which has the highest morbidity and mortality in Chinese population. Gefitinib, a tyrosine kinase (TK inhibitor of epidermal growth factor receptor (EGFR, displays anti-tumor activity. The present data regarding first-line treatment with single agent gefitinib against non-small-cell lung cancer (NSCLC in Chinese population are not sufficient. Purpose To assess the efficacy and toxicity of gefitinib in Chinese patients with advanced non-small-cell lung cancer (NSCLC, a study of single agent treatment with gefitinib in Chinese patients was conducted. Methods 45 patients with advanced NSCLC were treated with gefitinib (250 mg daily until the disease progression or intolerable toxicity. Results Among the 45 patients, 15 patients achieved partial response (PR, 17 patients experienced stable disease (SD, and 13 patients developed progression disease (PD. None of the patients achieved complete response (CR. The tumor response rate and disease control rate was 33% and 71.1%, respectively. Symptom remission rate was 72.5%, and median remission time was 8 days. Median overall survival and median progression-free survival was 15.3 months and 6.0 months, respectively. The main induced toxicities by gefitinib were skin rash and diarrhea (53.3% and 33.3%, respectively. The minor induced toxicities included dehydration and pruritus of skin (26.7% and 22.2%, respectively. In addition, hepatic toxicity and oral ulceration occurred in few patients (6.7% and 4.4%2, respectively. Conclusions Single agent treatment with gefitinib is effective and well tolerated in Chinese patients with advanced NSCLC.

Unusual lipid structures selectively reduce the toxicity of amphotericin B

International Nuclear Information System (INIS)

Janoff, A.S.; Boni, L.T.; Popescu, M.C.

1988-01-01

Ribbon-like structures result when amphotericin B interacts with lipid in an aqueous environment. At high ratios of amphotericin to lipid these structures, which are lipid-stabilized amphotericin aggregates, become prevalent resulting in a dramatic attenuation of amphotericin-mediated mammalian cell, but not fungal cell, toxicity. Studies utilizing freeze-etch electron microscopy, differential scanning calorimetry, 31 P NMR, x-ray diffraction, and optical spectroscopy revealed that this toxicity attenuation is related to the macromolecular structure of the complexes in a definable fashion. It is likely that amphotericin in this specific form will have a much improved therapeutic utility

Hyperthyroidism caused by a toxic intrathoracic goiter with a normal-sized cervical thyroid gland

International Nuclear Information System (INIS)

Prakash, R.; Lakshmipathi, N.; Jena, A.; Behari, V.; Chopra, M.K.

1986-01-01

The rare presentation of hyperthyroidism caused by an intrathoracic goiter with a normal-sized cervical thyroid gland is described. The toxic intrathoracic goiter demonstrated avid uptake of [ 131 I] and [99mTc]pertechnetate, with comparatively faint isotopic accumulation seen in the cervical thyroid. A chest roentgenogram and radioisotope scan should be mandatory in cases of hyperthyroidism having no cervical thyroid enlargement to explore the possibility of a toxic intrathoracic goiter

Abatement by Naringenin of Doxorubicin-Induced Cardiac Toxicity in Rats

International Nuclear Information System (INIS)

Arafa, H.M.; Abd-Ellah, M.F.; Hafez, H.F.

2005-01-01

Doxorubicin is one of the most active cytotoxic agents in current use. It has proven efficacy in various malignancies either alone or combined with other cytocidal agents. The clinical usefulness of the anthracycline drug has been precluded by cardiac toxicity. Many therapeutic interventions have been attempted to improve the therapeutic benefits of the drug. Few, however, have been efficacious in this setting. Purpose: We have addressed in the current study the possible protective effects of naringenin, a flavonoid known to have anti-oxidant properties, on doxorubicin induced cardiac toxicity in male Swiss albino rats. Methods: Forty male Swiss albino rats were used in this study. Naringenin (25 mg/kg body weight) was administered daily by gavage for 7 consecutive days before a cumulative single dose of doxorubicin (15 mg/kg body weight, ip). Doxorubicin induced marked biochemical alterations characteristic of cardiac toxicity including, elevated activities of serum total lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), enhanced lipid peroxidation measured as malonaldehyde (MDA). The anthracycline drug has also reduced the cardiac enzymatic activities of superoxide dismutase (SOD), glutathione-Stransferase (GST) and catalase (CAT). Besides, it reduced significantly the reduced glutathione (GSH) level, but it increased the total NO content in heart tissue. Prior administration of naringenin ahead of doxorubicin challenge ameliorated all these biochemical markers. Taken together, one could conclude that naringenin has a protective role in the abatement of doxorubicin-induced cardiac toxicity that resides, at least in part, on its anti-radical effects and regulatory role on NO production

Portable, accurate toxicity testing

International Nuclear Information System (INIS)

Sabate, R.W.; Stiffey, A.V.; Dewailly, E.L.; Hinds, A.A.; Vieaux, G.J.

1994-01-01

Ever tightening environmental regulations, severe penalties for non-compliance, and expensive remediation costs have stimulated development of methods to detect and measure toxins. Most of these methods are bioassays that must be performed in the laboratory; none previously devised has been truly portable. The US Army, through the Small Business Innovative Research program, has developed a hand-held, field deployable unit for testing toxicity of battlefield water supplies. This patented system employs the measurable quenching, in the presence of toxins, of the natural bioluminescence produced by the marine dinoflagellate alga Pyrocystis lunula. The procedure's inventor used it for years to measure toxicity concentrations of chemical warfare agents actually, their simulants, primarily in the form of pesticides and herbicides plus assorted toxic reagents, waterbottom samples, drilling fluids, even blood. While the procedure is more precise, cheaper, and faster than most bioassays, until recently it was immobile. Now it is deployable in the field. The laboratory apparatus has been proven to be sensitive to toxins in concentrations as low as a few parts per billion, repeatable within a variation of 10% or less, and unlike some other bioassays effective in turbid or colored media. The laboratory apparatus and the hand-held tester have been calibrated with the EPA protocol that uses the shrimplike Mysidopsis bahia. The test organism tolerates transportation well, but must be rested a few hours at the test site for regeneration of its light-producing powers. Toxicity now can be measured confidently in soils, water columns, discharge points, and many other media in situ. Most significant to the oil industry is that drilling fluids can be monitored continuously on the rig

Chemical warfare agent simulants for human volunteer trials of emergency decontamination: A systematic review.

Science.gov (United States)

James, Thomas; Wyke, Stacey; Marczylo, Tim; Collins, Samuel; Gaulton, Tom; Foxall, Kerry; Amlôt, Richard; Duarte-Davidson, Raquel

2018-01-01

Incidents involving the release of chemical agents can pose significant risks to public health. In such an event, emergency decontamination of affected casualties may need to be undertaken to reduce injury and possible loss of life. To ensure these methods are effective, human volunteer trials (HVTs) of decontamination protocols, using simulant contaminants, have been conducted. Simulants must be used to mimic the physicochemical properties of more harmful chemicals, while remaining non-toxic at the dose applied. This review focuses on studies that employed chemical warfare agent simulants in decontamination contexts, to identify those simulants most suitable for use in HVTs of emergency decontamination. Twenty-two simulants were identified, of which 17 were determined unsuitable for use in HVTs. The remaining simulants (n = 5) were further scrutinized for potential suitability according to toxicity, physicochemical properties and similarities to their equivalent toxic counterparts. Three suitable simulants, for use in HVTs were identified; methyl salicylate (simulant for sulphur mustard), diethyl malonate (simulant for soman) and malathion (simulant for VX or toxic industrial chemicals). All have been safely used in previous HVTs, and have a range of physicochemical properties that would allow useful inference to more toxic chemicals when employed in future studies of emergency decontamination systems. © 2017 Crown Copyright. Journal of Applied Toxicology published by John Wiley & Sons, Ltd.

Toxicity studies on the radioprotective agent WR-2721 in CDF1 mice and beagle dogs

International Nuclear Information System (INIS)

Palmer, T.E.; Glaza, S.M.; Dickie, B.C.; Weltman, R.H.; Greenspun, K.S.

1985-01-01

WR-2721, S-2-(3-aminopropylamino)ethylphosphorothioic acid, is used extensively to protect normal cells during the irradiation of neoplastic cells. Dose levels for human radiotherapy are based on results obtained from laboratory animal lethality and toxicity studies. WR-2721 was administered intravenously to CDF1 mice and beagle dogs. Single dose lethality studies in mice showed the average 1/10 of the lethal dose, the median lethal dose and 9/10 the lethal dose to be 508 (1523 mg/m2), 589 (1766 mg/m2), and 682 mg/kg (2047 mg/m2), respectively. The lethal dose for female mice was lower than that for males. The 1/10 lethal dose in mice was slightly toxic to dogs; 1/10 of that dose was nontoxic. The lethal dose for dogs (6000 mg/m2) was higher than that for mice (2000 mg/m2). Clinical signs of toxicosis in the single-dose mouse toxicity study were evident in the 1st week following treatment and declined during the recovery period; signs of toxicosis were transient in dogs. Acute drug-induced pathologic changes included elevated BUN and SGOT levels, lymphoid necrosis, and renal tubular degeneration in mice. These changes were evident in the 1st week following treatment, but had dissipated by study termination. Generalized vascular changes (congestion, hemorrhage, and edema) and renal tubular degeneration occurred in treated dogs that had died or were killed moribund 7 days postinjection. These findings indicate sex-dependent and interspecies variation in the toxicity of WR-2721 with acute, but reversible, pathologic changes

A new anticancer agent--{sup 131}I BGTP

Energy Technology Data Exchange (ETDEWEB)

Jiaheng, He; Shubin, Jiang; Guanquan, Wang [China Academy of Engineering Physics, Mianyang (China). Inst. of Nuclear Physics and Chemistry

2007-12-15

A new anticancer precursor, di-peptide[p-Boc-Gly-Tyr-NH(CH{sub 2}){sub 2} NH-PO (ONH{sub 4})-O-PhI*], was synthesized and labelled with {sup 131}I using enveloped-tube technique, the labelling yield could reach 85%. Using cell coalescent method, the biological activity in vitro of the labelled compounds was evaluated, showing that the primary appetency was kept and not damaged obviously during labelling. Results on judgement of their stability, lipophilicity and toxicity demonstrated lower toxicity, higher lipophilicity and lower iodium disassociation percentage (<12% after 72 h); furthermore, a tumour-bearing animal model, was establishd successfully, on which, the biological properties of the labelled agent was studied. (authors)

Toxicity bioassay and effects of sub-lethal exposure of malathion on ...

African Journals Online (AJOL)

Ksu-network

2012-04-26

Apr 26, 2012 ... glutamate pyruvic transaminase. Non-target animals including fish are greatly affected by the indiscriminate use of these pesticides. Fish appear to posses the same biochemical pathways to deal with the toxic effects of endogenous and exogenous agents as mammalian species does (Lackner, 1998).

Dose-dependent transitions in mechanisms of toxicity: case studies

International Nuclear Information System (INIS)

Slikker, William; Andersen, Melvin E.; Bogdanffy, Matthew S.; Bus, James S.; Cohen, Steven D.; Conolly, Rory B.; David, Raymond M.; Doerrer, Nancy G.; Dorman, David C.; Gaylor, David W.; Hattis, Dale; Rogers, John M.; Setzer, R. Woodrow; Swenberg, James A.; Wallace, Kendall

2004-01-01

Experience with dose response and mechanisms of toxicity has shown that multiple mechanisms may exist for a single agent along the continuum of the full dose-response curve. It is highly likely that critical, limiting steps in any given mechanistic pathway may become overwhelmed with increasing exposures, signaling the emergence of new modalities of toxic tissue injury at these higher doses. Therefore, dose-dependent transitions in principal mechanisms of toxicity may occur, and could have significant impact on the interpretation of reference data sets for risk assessment. To illustrate the existence of dose-dependent transitions in mechanisms of toxicity, a group of academic, government, and industry scientists, formed under the leadership of the ILSI Health and Environmental Sciences Institute (HESI), developed a series of case studies. These case studies included acetaminophen, butadiene, ethylene glycol, formaldehyde, manganese, methylene chloride, peroxisome proliferator-activated receptor (PPAR), progesterone/hydroxyflutamide, propylene oxide, vinyl acetate, vinyl chloride, vinylidene chloride, and zinc. The case studies formed the basis for technical discourse at two scientific workshops in 2003

Microplastic potentiates triclosan toxicity to the marine copepod Acartia tonsa (Dana)

DEFF Research Database (Denmark)

Syberg, Kristian; Nielsen, Anne; Khan, Farhan

2017-01-01

Microplastics (MP) are contaminants of environmental concern partly due to plastics ability to sorb and transport hydrophobic organic contaminants (HOC). The importance of this "vector effect" is currently being debated in the scientific community. This debate largely ignores that the co-exposure......Microplastics (MP) are contaminants of environmental concern partly due to plastics ability to sorb and transport hydrophobic organic contaminants (HOC). The importance of this "vector effect" is currently being debated in the scientific community. This debate largely ignores that the co......-exposures of MP and HOC are mixtures of hazardous agents, which can be addressed from a mixture toxicity perspective. In this study, mixture effects of polyethylene microbeads (MP) and triclosan (TCS) (a commonly used antibacterial agent in cosmetics) were assessed on the marine copepod Acartia tonsa. Data...... indicated that MP potentiate the toxicity of TCS, illustrating the importance of understanding the mixture interaction between plastics and HOC when addressing the environmental importance of the vector effect....

Nanodiamond-Manganese dual mode MRI contrast agents for enhanced liver tumor detection.

Science.gov (United States)

Hou, Weixin; Toh, Tan Boon; Abdullah, Lissa Nurrul; Yvonne, Tay Wei Zheng; Lee, Kuan J; Guenther, Ilonka; Chow, Edward Kai-Hua

2017-04-01

Contrast agent-enhanced magnetic resonance (MR) imaging is critical for the diagnosis and monitoring of a number of diseases, including cancer. Certain clinical applications, including the detection of liver tumors, rely on both T1 and T2-weighted images even though contrast agent-enhanced MR imaging is not always reliable. Thus, there is a need for improved dual mode contrast agents with enhanced sensitivity. We report the development of a nanodiamond-manganese dual mode contrast agent that enhanced both T1 and T2-weighted MR imaging. Conjugation of manganese to nanodiamonds resulted in improved longitudinal and transverse relaxivity efficacy over unmodified MnCl 2 as well as clinical contrast agents. Following intravenous administration, nanodiamond-manganese complexes outperformed current clinical contrast agents in an orthotopic liver cancer mouse model while also reducing blood serum concentration of toxic free Mn 2+ ions. Thus, nanodiamond-manganese complexes may serve as more effective dual mode MRI contrast agent, particularly in cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Antimicrobial Activity and Toxicity of Zhumeria Majdae Essential Oil and its Capsulated Form

Directory of Open Access Journals (Sweden)

Rahil Emami

2015-03-01

Conclusion: It was found that in some cases, encapsulation could lead to better antimicrobial property and less toxicity. Because of high antimicrobial activity, both EO and EFEO of Zhumeria majdae may be used as powerfully antimicrobial agents.

An Agent Based Collaborative Simplification of 3D Mesh Model

Science.gov (United States)

Wang, Li-Rong; Yu, Bo; Hagiwara, Ichiro

Large-volume mesh model faces the challenge in fast rendering and transmission by Internet. The current mesh models obtained by using three-dimensional (3D) scanning technology are usually very large in data volume. This paper develops a mobile agent based collaborative environment on the development platform of mobile-C. Communication among distributed agents includes grasping image of visualized mesh model, annotation to grasped image and instant message. Remote and collaborative simplification can be efficiently conducted by Internet.

Anaerobic toxicity of cationic silver nanoparticles

International Nuclear Information System (INIS)

Gitipour, Alireza; Thiel, Stephen W.; Scheckel, Kirk G.; Tolaymat, Thabet

2016-01-01

The microbial toxicity of silver nanoparticles (AgNPs) stabilized with different capping agents was compared to that of Ag"+ under anaerobic conditions. Three AgNPs were investigated: (1) negatively charged citrate-coated AgNPs (citrate-AgNPs), (2) minimally charged polyvinylpyrrolidone coated AgNPs (PVP-AgNPs) and (3) positively charged branched polyethyleneimine coated AgNPs (BPEI-AgNPs). The AgNPs investigated in this experiment were similar in size (10–15 nm), spherical in shape, but varied in surface charge which ranged from highly negative to highly positive. While, at AgNPs concentrations lower than 5 mg L"−"1, the anaerobic decomposition process was not influenced by the presence of the nanoparticles, there was an observed impact on the diversity of the microbial community. At elevated concentrations (100 mg L"−"1 as silver), only the cationic BPEI-AgNPs demonstrated toxicity similar in magnitude to that of Ag"+. Both citrate and PVP-AgNPs did not exhibit toxicity at the 100 mg L"−"1 as measured by biogas evolution. These findings further indicate the varying modes of action for nanoparticle toxicity and represent one of the few studies that evaluate end-of-life management concerns with regards to the increasing use of nanomaterials in our everyday life. These findings also highlight some of the concerns with a one size fits all approach to the evaluation of environmental health and safety concerns associated with the use of nanoparticles. - Highlights: • At concentrations -1 the anaerobic decomposition process was not impacted. • An impact on the microbial community at concentrations -1 were observed. • At high concentrations (100 mg L"−"1), the cationic BPEI-AgNPs demonstrated toxicity. • Toxicity was demonstrated without the presence of oxidative dissolution of silver. • A one size fits all approach for the evaluation of NPs may not be accurate.

LITHIUM TOXICITY IN ELDERLY-A CASE REPORT AND DISCUSSION

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Mariana D. Arnaoudova

2014-07-01

Full Text Available Background: The therapeutic effect of Lithium as a mono therapy or as an augmenting agent in a variety of medical and psychiatric disorders is under doubt. However, lithium is associated with a number of adverse effects. Method and objective: A review of the literature on lithium use in older adults and a case report presentation. Summary of results: The literature, concerning current uses of Lithium in older patients, especially for patients with neurologic or cognitive impairments is limited due to the lack of well-designed, large clinical trials. Elderly patients are at higher risk to develop neurotoxicity in the course of lithium therapy. We present a case of 66 years old female patient, suffering bipolar disorder, who developed lithium toxicity and was admitted at the gerontopsychiatric department due to a confusional state, tremor and gait abnormality. Lithium toxicity was suspected when sufficient information about previous medical history of lithium therapy has been obtained. Lithium level found to be 1.69mmol/L. The patient has developed intoxication during maintenance therapy with a lithium dosage which had been unchanged for months. Conclusion: Elderly patients require lower doses of Lithium to achieve similar serum concentrations as those in younger adults. Neurotoxicity could be suspected at serum lithium levels which are considered therapeutic in younger adults. When prescribing lithium agents in elderly we should consider age-related changes in pharmacokinetics. The best way to prevent lithium toxicity is to control the serum concentration regularly during therapy.

The Scarlet Letter of Alkylation: A Mini Review of Selective Alkylating Agents

OpenAIRE

Oronsky, Bryan T; Reid, Tony; Knox, Susan J; Scicinski, Jan J

2012-01-01

If there were a stigma scale for chemotherapy, alkylating agents would be ranked at the top of the list. The chemical term alkylation is associated with nonselective toxicity, an association that dates back to the use of nitrogen mustards during World War I as chemical warfare agents. That this stigma persists and extends to compounds that, through selectivity, attempt to “tame” the indiscriminate destructive potential of alkylation is the subject of this review. Selective alkylation, as it i...

Evaluation of pawpaw leaves extract as anti-corrosion agent for ...

African Journals Online (AJOL)

Pawpaw leaves extract was examined as anti-corrosion agent for aluminium in hydrochloric acid medium. The extract and corrosion product were analyzed using Fourier transform infrared spectrophotometer (FTIR). Thermometric, gravimetric, potentiodynamic polarization and scanning electron microscopic methods were ...

Sensing and capture of toxic and hazardous gases and vapors by metal-organic frameworks.

Science.gov (United States)

Wang, Hao; Lustig, William P; Li, Jing

2018-03-13

Toxic and hazardous chemical species are ubiquitous, predominantly emitted by anthropogenic activities, and pose serious risks to human health and the environment. Thus, the sensing and subsequent capture of these chemicals, especially in the gas or vapor phase, are of extreme importance. To this end, metal-organic frameworks have attracted significant interest, as their high porosity and wide tunability make them ideal for both applications. These tailorable framework materials are particularly promising for the specific sensing and capture of targeted chemicals, as they can be designed to fit a diverse range of required conditions. This review will discuss the advantages of metal-organic frameworks in the sensing and capture of harmful gases and vapors, as well as principles and strategies guiding the design of these materials. Recent progress in the luminescent detection of aromatic and aliphatic volatile organic compounds, toxic gases, and chemical warfare agents will be summarized, and the adsorptive removal of fluorocarbons/chlorofluorocarbons, volatile radioactive species, toxic industrial gases and chemical warfare agents will be discussed.

Prospective evaluation of the super scan of metabolic bone disease (abstract)

International Nuclear Information System (INIS)

Khan, A.U.; Ahmad, S.; Khan, A.A.; Khan, S.M.; Rauf, M.

1999-01-01

A total of 27 cases (23 females and 4 males) having super scan of metabolic bone disease were prospectively evaluated over a period of 2 years (Jan. 1997 to Dec. 1998) at the Nuclear Medicine Department (NMD), institute of Radiotherapy and Nuclear Medicine (IRNUM), Peshawar to identify various causes for the super scan picture on Tc-99m MDP bone scintigraphy in our clinical environment. After the three observer confirmation of the bone scan, the serum calcium and Parathyroid Hormone (PTH) estimation was done. The patients having serum PTH greater than 250 Pg/L under went two phase Parathyroid MIBI Scintigraphy 2PP MIBI scan) for the detection of parathyroid adenoma. The patients having positive scans for parathyroid Adenoma were subjected to surgery and histopathological confirmation was obtained. Selected cases under went a trial of deport preparation of vitamin D3 calcium supplementation. The final diagnosis of 16 patients was osteomalacia (59%), six patients had histopathologically confirmed parathyroid adenoma (22.2%), one case each was that of toxic thyroid adenoma (3.7%) and chronic renal failure (3.7%). In three cases the final diagnosis was not reached (11.21%). Osteomalacia and parathyroid adenoma are the two most common causes for the super scan picture on bone scintigraphy. (author)

Benzimidazole derivatives: search for GI-friendly anti-inflammatory analgesic agents

Directory of Open Access Journals (Sweden)

Monika Gaba

2015-07-01

Full Text Available Non-steroidal anti-inflammatory drugs (NSAIDs have been successfully used for the alleviation of pain and inflammation in the past and continue to be used daily by millions of patients worldwide. However, gastrointestinal (GI toxicity associated with NSAIDs is an important medical and socioeconomic problem. Local generation of various reactive oxygen species plays a significant role in the formation of gastric ulceration associated with NSAIDs therapy. Co-medication of antioxidants along with NSAIDs has been found to be beneficial in the prevention of GI injury. This paper describes the synthesis and biological evaluation of N-1-(phenylsulfonyl-2-methylamino-substituted-1H-benzimidazole derivatives as anti-inflammatory analgesic agents with lower GI toxicity. Studies in vitro and in vivo demonstrated that the antioxidant activity of the test compounds decreased GI toxicity.

Recent advances in evaluation of oxime efficacy in nerve agent poisoning by in vitro analysis

International Nuclear Information System (INIS)

Worek, F.; Eyer, P.; Aurbek, N.; Szinicz, L.; Thiermann, H.

2007-01-01

The availability of highly toxic organophosphorus (OP) warfare agents (nerve agents) underlines the necessity for an effective medical treatment. Acute OP toxicity is primarily caused by inhibition of acetylcholinesterase (AChE). Reactivators (oximes) of inhibited AChE are a mainstay of treatment, however, the commercially available compounds, obidoxime and pralidoxime, are considered to be rather ineffective against various nerve agents, e.g. soman and cyclosarin. This led to the synthesis and investigation of numerous oximes in the past decades. Reactivation of OP-inhibited AChE is considered to be the most important reaction of oximes. Clinical data from studies with pesticide-poisoned patients support the assumption that the various reactions between AChE, OP and oxime, i.e. inhibition, reactivation and aging, can be investigated in vitro with human AChE. In contrast to animal experiments such in vitro studies with human tissue enable the evaluation of oxime efficacy without being affected by species differences. In the past few years numerous in vitro studies were performed by different groups with a large number of oximes and methods were developed for extrapolating in vitro data to different scenarios of human nerve agent poisoning. The present status in the evaluation of new oximes as antidotes against nerve agent poisoning will be discussed

The effects of water soluble contrast agents on the respiratory tract

International Nuclear Information System (INIS)

Lovett, I.; Donchey, S.; Doust, B.; Branson, J.; Munro, V.

1989-01-01

The water soluble contrast agents Gastrografin R (Sodium diatrizoate and meglumine diatrizoate, Schering, Berlin), Iopamiro 300 R (Iopamidol, Schering, Berlin), and Dionosil Aqueous R (propyliodone BP, Glaxo, England) were instilled into the tracheobronchial tree of rats in doses of either 0.1 ml and 0.25 ml. Rats being used as controls, underwent sham operations with the instillation of air instead of contrast agent. In all, 85 rats were used. All rats that had not already died from the effects of contrast agent were sacrificed 30 minutes after instillation. The relative effects of the contrast agents were measured by comparing: survival time; radiographic effects of the contrast agents on the lungs; and pathological changes as estimated by post mortem lung section and microscopy. The least toxic agent was the one with the lowest osmotic activity, namely Aqueous Dionosil. It is therefore recommended that Aqueous Dionosil be used in preference to Gastrografin or Iopamidol for studies of the oesophagus whenever there is a danger of aspiration of contrast agent into the tracheobronchial tree. 11 refs., 3 figs., 5 tabs

SYNTHESIS, THERMAL STUDIES AND CONVERSION DEGREE OF DIMETHACRYLATE POLYMERS USING NEW NON-TOXIC COINITIATORS

Directory of Open Access Journals (Sweden)

Rafael Turra Alarcon

Full Text Available The aim of this paper is to replace toxic coinitiators (tertiary amines by non-toxic compounds such as glycerol and inositol (polyalcohol in dimethacrylate resins. For this purpose, mid infrared spectroscopy (MIR was used to calculate the monomers' degree of conversion (%DC; as well as simultaneous Thermogravimetric Analysis – Differential Thermal Analysis (TGA-DTA and Differential Scanning Calorimetry (DSC were conducted to evaluate thermal stability, degradation steps, and thermal events. The use of different initiator systems did not modify the thermal events or the thermal stability of each of the dimethacrylate resins. Results show a substitution of system 2 (toxicity by system 3 (low toxicity, which had a good conversion velocity and total conversion in some monomers, is plausible.

Ocular Toxicity Profile of ST-162 and ST-168 as Novel Bifunctional MEK/PI3K Inhibitors.

Science.gov (United States)

Smith, Andrew; Pawar, Mercy; Van Dort, Marcian E; Galbán, Stefanie; Welton, Amanda R; Thurber, Greg M; Ross, Brian D; Besirli, Cagri G

2018-04-30

ST-162 and ST-168 are small-molecule bifunctional inhibitors of MEK and PI3K signaling pathways that are being developed as novel antitumor agents. Previous small-molecule and biologic MEK inhibitors demonstrated ocular toxicity events that were dose limiting in clinical studies. We evaluated in vitro and in vivo ocular toxicity profiles of ST-162 and ST-168. Photoreceptor cell line 661W and adult retinal pigment epithelium cell line ARPE-19 were treated with increasing concentrations of bifunctional inhibitors. Western blots, cell viability, and caspase activity assays were performed to evaluate MEK and PI3K inhibition and dose-dependent in vitro toxicity, and compared with monotherapy. In vivo toxicity profile was assessed by intravitreal injection of ST-162 and ST-168 in Dutch-Belted rabbits, followed by ocular examination and histological analysis of enucleated eyes. Retinal cell lines treated with ST-162 or ST-168 exhibited dose-dependent inhibition of MEK and PI3K signaling. Compared with inhibition by monotherapies and their combinations, bifunctional inhibitors demonstrated reduced cell death and caspase activity. In vivo, both bifunctional inhibitors exhibited a more favorable toxicity profile when compared with MEK inhibitor PD0325901. Novel MEK and PI3K bifunctional inhibitors ST-162 and ST-168 demonstrate favorable in vitro and in vivo ocular toxicity profiles, supporting their further development as potential therapeutic agents targeting multiple aggressive tumors.

Immunological changes following a combined effect of chromic small dose γ-irradiation and toxic agents

International Nuclear Information System (INIS)

Shubik, V.M.; Zykova, I.A.

1981-01-01

Immunologic changes under conditions of durable effect of low dose γ-radiation on people in the case of combining radiation with the effect of low concentrations of toxic substances, are studied. Under the above effect, the appearance of deviations from the side of immunologic status is possible. Taking into account the important role of the immunity system in homeostasis preservation and the formation of a series of pathological states it is advisable to use figures, and characteristics inherent in the state of the cell immunity to autoallergic processes to estimate a combined effect of radiation and toxic substances on the organism of people [ru

Combinatorial Libraries As a Tool for the Discovery of Novel, Broad-Spectrum Antibacterial Agents Targeting the ESKAPE Pathogens.

Science.gov (United States)

Fleeman, Renee; LaVoi, Travis M; Santos, Radleigh G; Morales, Angela; Nefzi, Adel; Welmaker, Gregory S; Medina-Franco, José L; Giulianotti, Marc A; Houghten, Richard A; Shaw, Lindsey N

2015-04-23

Mixture based synthetic combinatorial libraries offer a tremendous enhancement for the rate of drug discovery, allowing the activity of millions of compounds to be assessed through the testing of exponentially fewer samples. In this study, we used a scaffold-ranking library to screen 37 different libraries for antibacterial activity against the ESKAPE pathogens. Each library contained between 10000 and 750000 structural analogues for a total of >6 million compounds. From this, we identified a bis-cyclic guanidine library that displayed strong antibacterial activity. A positional scanning library for these compounds was developed and used to identify the most effective functional groups at each variant position. Individual compounds were synthesized that were broadly active against all ESKAPE organisms at concentrations development of resistance, and displayed almost no toxicity when tested against human lung cells and erythrocytes. Using a murine model of peritonitis, we also demonstrate that these agents are highly efficacious in vivo.

Valorization of titanium metal wastes as tanning agent used in leather industry.

Science.gov (United States)

Crudu, Marian; Deselnicu, Viorica; Deselnicu, Dana Corina; Albu, Luminita

2014-10-01

The development of new tanning agents and new technologies in the leather sector is required to cope with the increasingly higher environmental pressure on the current tanning materials and processes such as tanning with chromium salts. In this paper, the use of titanium wastes (cuttings) resulting from the process of obtaining highly pure titanium (ingots), for the synthesis of new tanning agent and tanning bovine hides with new tanning agent, as alternative to tanning with chromium salts are investigated. For this purpose, Ti waste and Ti-based tanning agent were characterized for metal content by inductively coupled plasma mass spectrometry (ICP-MS) and chemical analysis; the tanned leather (wet white leather) was characterized by Scanning Electron Microscope/Energy Dispersive Using X-ray (Analysis). SEM/EDX analysis for metal content; Differential scanning calorimetric (DSC), Micro-Hot-Table and standard shrinkage temperature showing a hydrothermal stability (ranged from 75.3 to 77°C) and chemical analysis showing the leather is tanned and can be processed through the subsequent mechanical operations (splitting, shaving). On the other hand, an analysis of major minor trace substances from Ti-end waste (especially vanadium content) in new tanning agent and wet white leather (not detected) and residue stream was performed and showed that leachability of vanadium is acceptable. The results obtained show that new tanning agent obtained from Ti end waste can be used for tanning bovine hides, as eco-friendly alternative for chrome tanning. Copyright © 2014 Elsevier Ltd. All rights reserved.

Advances in the use of biologic agents for the treatment of systemic vasculitis

Science.gov (United States)

Chung, Sharon A.; Seo, Philip

2010-01-01

Purpose of review Due to the well-known toxicities of cyclophosphamide, substantial interest exists in finding other therapies to treat primary systemic vasculitis. Biologic agents have been proposed as an alternative to cyclophosphamide for these disorders because of their recent success in treating other rheumatic diseases. This article reviews the current state-of-the-art with regards to the use of biologic agents as a treatment for systemic vasculitis. Recent findings The greatest amount of experience with these agents for the treatment of systemic vasculitis is with anti-tumor necrosis factor agents, pooled intravenous immunoglobulin, and anti-B cell therapies such as rituximab. Intravenous immunoglobulin is already a standard therapy for Kawasaki's disease, but should also be considered for the treatment of ANCA-associated vasculitis when standard therapies are either ineffective or contraindicated. Early experience with tumor necrosis factor inhibitors indicates that they may be effective for the treatment of Takayasu's arteritis, but their role in the treatment of other forms of vasculitis remains controversial. Early experience with rituximab for the treatment of several forms of vasculitis has been quite promising, but must be confirmed by ongoing randomized clinical trials. Summary Biologic agents represent the next evolution in treatment for the primary systemic vasculitides. Greater understanding of these diseases has allowed use to move further away from non-specific, highly toxic therapies towards a more directed approach. As our experience with these agents increases, they will likely form the keystone of treatment in the near future. PMID:19077713

A functionalized superparamagnetic iron oxide colloid as a receptor directed MR contrast agent

International Nuclear Information System (INIS)

Josephson, L.; Groman, E.V.; Menz, E.; Lewis, J.M.; Bengele, H.

1990-01-01

We have synthesized a surface functionalized superparamagnetic iron oxide colloid whose clearance from the vascular compartment was inhibited by asialofetuin but not fetuin. Unlike other particulate or colloidal magnetic resonance (MR) contrast agents, the agent of the current communication is not withdrawn from the vascular compartment by cells of the macrophage-monocyte phagocytic system, as indicated by its selective increase in hepatic relaxation rates. Because of this we refer to this colloid as a hepatic selective (HS) MR contrast agent. At 20 mumol Fe/kg the HS MR agent darkened MR images of liver. The HS MR agent exhibited no acute toxicity when injected into rats at 1800 mumol Fe/kg. Based on these observations, surface functionalized superparamagnetic iron oxide colloids may be the basis of MR contrast agents internalized by receptor mediated endocytosis generally, and by the asialoglycoprotein receptor in particular

Serotonin Toxicity Caused by Moclobemide Too Soon After Paroxetine-Selegiline

Directory of Open Access Journals (Sweden)

Ming-Ling Wu

2009-08-01

Full Text Available Serotonin toxicity is an iatrogenic complication of serotonergic drug therapy. It is due to an overstimulation of central and peripheral serotonin receptors that lead to neuromuscular, mental and autonomic changes. Moclobemide is a reversible inhibitor of monoamine oxidase (MAO-A, selegiline is an irreversible selective inhibitor of MAO-B, and paroxetine is a selective serotonin reuptake inhibitor. Combined use of these agents is known to cause serotonin toxicity. A 53-year-old woman had been treated with paroxetine and selegiline. After moclobemide was prescribed in place of paroxetine without a washout period, she quickly developed confusion, agitation, ataxia, diaphoresis, tremor, mydriasis, ocular clonus, hyper-reflexia, tachycardia, moderately elevated blood pressure and high fever, symptoms that were consistent with serotonin toxicity. Discontinuation of the drugs, hydration and supportive care were followed by remarkable improvement of baseline status within 3 days. This case demonstrates that serotonin toxicity may occur even with small doses of paroxetine, selegi-line and moclobemide in combination. Physicians managing patients with depression must be aware of the potential for serotonin toxicity and should be able to recognize and treat or, ideally, anticipate and avoid this pharmacodynamically-mediated interaction that may occur between prescribed drugs.

Design and properties of a novel nucleating agent for isotactic polypropylene

International Nuclear Information System (INIS)

Lv, Zhiping; Yang, Yunfei; Wu, Ran; Tong, Yuchao

2012-01-01

Highlights: ► Three new nucleating agents which is structurally similar to Al-PTBBA were prepared. ► These three nucleating agents were very effective in increasing T c and X c of iPP. ► Great improvement of mechanical properties of nucleated iPP was also obtained. ► Nucleating agent TSD was the most effective nucleating agent for iPP. -- Abstract: Three new nucleating agents TB, TD and TSD (titanate of benzoate or 4-tert-Butylbenzoate) were prepared. Isotactic polypropylene (iPP) nucleated were studied by using thermogravimetry analysis (TGA), X-ray diffraction analysis (XRD), differential scanning calorimetry (DSC) and polarized light microscopy (PLM). The mechanical properties and Vicat softening temperature (VST) of iPP were also tested. The results indicated that these three nucleating agents were very effective in increasing the crystallization temperature (T c ) and crystallinity (X c ) of iPP. Mechanical properties of nucleated iPP were improved remarkably, especially nucleating agent TSD.

Radioprotective and radiotherapeutic properties of biotechnological agent MD2

International Nuclear Information System (INIS)

Sobol, C.V.; Komar, V.E.; Sobol, Y.T.

1996-01-01

In recent years as the result of nuclear testing and accidents at nuclear power plants such as Chernobyl, etc. radiation exposure has become a major issue in various parts of the world. Experience of recent nuclear accidents has shown there is no effective treatment for patients expose to doses of radiation that result in fatal hematopoietic failure and /or secondary infections. Therefore, agents that are effective when administered after irradiation, are of great interest. In this study, the possibility of using biotechnological agent MD2 after lethal total body irradiation (TBI) and radiotherapy has been demonstrated. In addition, the considerable radioprotection without toxic effect can be obtained. (author)

Forcing the vicious circle: sarcopenia increases toxicity, decreases response to chemotherapy and worsens with chemotherapy.

Science.gov (United States)

Bozzetti, F

2017-09-01

Sarcopenia has recently emerged as a new condition that, independently from malnutrition, may adversely affect the prognosis of cancer patients. Purpose of this narrative review is to define the prevalence of sarcopenia in different primaries, its role in leading to chemotherapy toxicity and decreased compliance with the oncological therapy and the effect of some drugs on the onset of sarcopenia. Finally, the review aims to describe the current approaches to restore the muscle mass through nutrition, exercise and anti-inflammatory agents or multimodal programmes with a special emphasis on the results of randomized controlled trials. The examination of the computed tomography scan at the level of the third lumbar vertebra-a common procedure for staging many tumours-has allowed the oncologist to evaluate the muscle mass and to collect many retrospective data on the prevalence of sarcopenia and its clinical consequences. Sarcopenia is a condition affecting a high percentage of patients with a range depending on type of primary tumour and stage of disease. It is noteworthy that patients may be sarcopenic even if their nutritional status is apparently maintained or they are obese. Sarcopenic patients exhibited higher chemotherapy toxicity and poorer compliance with oncological treatments. Furthermore, several antineoplastic drugs appeared to worsen the sarcopenic status. Therapeutic approaches are several and this review will focus on those validated by randomized controlled trials. They include the use of ω-3-enriched oral nutritional supplements and orexigenic agents, the administration of adequate high-protein regimens delivered enterally or parenterally, and programmes of physical exercise. Better results are expected combining different procedures in a multimodal approach. In conclusion, there are several premises to prevent/treat sarcopenia. The oncologist should coordinate this multimodal approach by selecting priorities and sequences of treatments and then

Deactivating Chemical Agents Using Enzyme-Coated Nanofibers Formed by Electrospinning

Science.gov (United States)

2016-01-01

7.3mM/mg). Key words Coaxial electrospinning, DFPase, Enzyme, chemical warfare , nanofiber, decontamination . Introduction Chemical warfare ...Krile, R.; Nishioka, M.; Taylor, M.; Riggs, K.; Stone, H. Decontamination of Toxic Industrial Chemicals and Chemical Warfare Agents On Building...298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 MATS COATINGS ELECTROSPINNING CHEMICAL WARFARE

Esophageal Toxicity From High-Dose, Single-Fraction Paraspinal Stereotactic Radiosurgery

International Nuclear Information System (INIS)

Cox, Brett W.; Jackson, Andrew; Hunt, Margie; Bilsky, Mark; Yamada, Yoshiya

2012-01-01

Purpose: To report the esophageal toxicity from single-fraction paraspinal stereotactic radiosurgery (SRS) and identify dosimetric and clinical risk factors for toxicity. Methods and Materials: A total of 204 spinal metastases abutting the esophagus (182 patients) were treated with high-dose single-fraction SRS during 2003-2010. Toxicity was scored using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 4.0. Dose-volume histograms were combined to generate a comprehensive atlas of complication incidence that identifies risk factors for toxicity. Correlation of dose-volume factors with esophageal toxicity was assessed using Fisher’s exact test and logistic regression. Clinical factors were correlated with toxicity. Results: The median dose to the planning treatment volume was 24 Gy. Median follow-up was 12 months (range, 3-81). There were 31 (15%) acute and 24 (12%) late esophageal toxicities. The rate of grade ≥3 acute or late toxicity was 6.8% (14 patients). Fisher’s exact test resulted in significant median splits for grade ≥3 toxicity at V12 = 3.78 cm 3 (relative risk [RR] 3.7, P=.05), V15 = 1.87 cm 3 (RR 13, P=.0013), V20 = 0.11 cm 3 (RR 6, P=0.01), and V22 = 0.0 cm 3 (RR 13, P=.0013). The median split for D2.5 cm 3 (14.02 Gy) was also a significant predictor of toxicity (RR 6; P=.01). A highly significant logistic regression model was generated on the basis of D2.5 cm 3 . One hundred percent (n = 7) of grade ≥4 toxicities were associated with radiation recall reactions after doxorubicin or gemcitabine chemotherapy or iatrogenic manipulation of the irradiated esophagus. Conclusions: High-dose, single-fraction paraspinal SRS has a low rate of grade ≥3 esophageal toxicity. Severe esophageal toxicity is minimized with careful attention to esophageal doses during treatment planning. Iatrogenic manipulation of the irradiated esophagus and systemic agents classically associated with radiation recall reactions are

Compound toxicity screening and structure-activity relationship modeling in Escherichia coli.

Science.gov (United States)

Planson, Anne-Gaëlle; Carbonell, Pablo; Paillard, Elodie; Pollet, Nicolas; Faulon, Jean-Loup

2012-03-01

Synthetic biology and metabolic engineering are used to develop new strategies for producing valuable compounds ranging from therapeutics to biofuels in engineered microorganisms. When developing methods for high-titer production cells, toxicity is an important element to consider. Indeed the production rate can be limited due to toxic intermediates or accumulation of byproducts of the heterologous biosynthetic pathway of interest. Conversely, highly toxic molecules are desired when designing antimicrobials. Compound toxicity in bacteria plays a major role in metabolic engineering as well as in the development of new antibacterial agents. Here, we screened a diversified chemical library of 166 compounds for toxicity in Escherichia coli. The dataset was built using a clustering algorithm maximizing the chemical diversity in the library. The resulting assay data was used to develop a toxicity predictor that we used to assess the toxicity of metabolites throughout the metabolome. This new tool for predicting toxicity can thus be used for fine-tuning heterologous expression and can be integrated in a computational-framework for metabolic pathway design. Many structure-activity relationship tools have been developed for toxicology studies in eukaryotes [Valerio (2009), Toxicol Appl Pharmacol, 241(3): 356-370], however, to the best of our knowledge we present here the first E. coli toxicity prediction web server based on QSAR models (EcoliTox server: http://www.issb.genopole.fr/∼faulon/EcoliTox.php). Copyright © 2011 Wiley Periodicals, Inc.

A novel natural analog in situ stabilization agent

International Nuclear Information System (INIS)

Shaw, P.

1995-01-01

This report summarizes the laboratory-scale test results on a synthetic analog of natural hematite cement for potential as an in situ treatment and stabilization agent for buried hazardous and radioactive waste. The concept is based on the principle that the ideal waste isolation materials are synthetic analogs of those natural encapsulating materials (cements), which are in equilibrium with the environment in which they occur. If equilibrium is achieved, then such materials will remain intact as long as the natural environment remains unchanged. The specific waste application is long-term stabilization of transuranic-contaminated waste pits and trenches at the Idaho National Engineering Laboratory (INEL). Six properties of the natural analog agent and resulting wasteforms are discussed to access the agent's effectiveness and implementability: hydraulic conductivity; compressive strength; mineralogy and microstructure; compatibility with possible waste materials, nitrates, machine cutting oil, and metallic iron; leachability of hazardous metals; and field application parameters. Data indicated that the iron waste encapsulation materials tested are appropriate choices for buried waste mixed with INEL soil. Iron oxide/gypsum INEL soil wasteforms have hydraulic conductivity values close to the regulatory limit. Wasteforms with soil and wastes have compressive strength greater than the regulatory minimum. Gypsum/iron oxide removes hazardous metals from solution by adsorption and would pass Toxicity Characteristic Leaching Procedure limits for most toxic metals. It appears to be chemically and physically inert with respect to the bulk of the waste materials likely to be found at INEL, and has properties conducive to jet grouting

Human contamination by persistent toxic substances: the rationale to improve exposure assessment.

Science.gov (United States)

Porta, Miquel

2015-10-01

We know quite a lot about the generalized human contamination by environmental chemical agents; this statement is fully compatible with the view that most countries lack the necessary monitoring systems. We also know quite a lot about the toxic effects of environmental pollutants; this statement is fully compatible with the proposal that we need both more research and more energetic policies to decrease human contamination by such pollutants. Unsurprisingly, we know too little about the (environmental and social) causes and the etiopathogenesis (mechanisms) of the most prevalent diseases, and we will continue to miss relevant causes and mechanisms if we neglect the toxic chemicals that commonly contaminate humans, worldwide. Basic, clinical end environmental-epidemiological research on human health should more often consider integrating biomarkers of internal dose of environmental chemical pollutants. When we act in more responsible, rational, and scientific ways; when we become less dismissive towards environmental hazards; and when we thus neglect less the generalized human contamination by environmental chemical agents and their toxic effects, we will expand mechanistic biologic knowledge, and we shall as well increase the effectiveness of interventions and policies that enable the primary prevention of human diseases which cause huge amounts of economic burden and human suffering.

Toxic fluoride gas emissions from lithium-ion battery fires.

Science.gov (United States)

Larsson, Fredrik; Andersson, Petra; Blomqvist, Per; Mellander, Bengt-Erik

2017-08-30

Lithium-ion battery fires generate intense heat and considerable amounts of gas and smoke. Although the emission of toxic gases can be a larger threat than the heat, the knowledge of such emissions is limited. This paper presents quantitative measurements of heat release and fluoride gas emissions during battery fires for seven different types of commercial lithium-ion batteries. The results have been validated using two independent measurement techniques and show that large amounts of hydrogen fluoride (HF) may be generated, ranging between 20 and 200 mg/Wh of nominal battery energy capacity. In addition, 15-22 mg/Wh of another potentially toxic gas, phosphoryl fluoride (POF 3 ), was measured in some of the fire tests. Gas emissions when using water mist as extinguishing agent were also investigated. Fluoride gas emission can pose a serious toxic threat and the results are crucial findings for risk assessment and management, especially for large Li-ion battery packs.

Multifunctional ultra-high vacuum apparatus for studies of the interactions of chemical warfare agents on complex surfaces

International Nuclear Information System (INIS)

Wilmsmeyer, Amanda R.; Morris, John R.; Gordon, Wesley O.; Mantooth, Brent A.; Lalain, Teri A.; Davis, Erin Durke

2014-01-01

A fundamental understanding of the surface chemistry of chemical warfare agents is needed to fully predict the interaction of these toxic molecules with militarily relevant materials, catalysts, and environmental surfaces. For example, rules for predicting the surface chemistry of agents can be applied to the creation of next generation decontaminants, reactive coatings, and protective materials for the warfighter. Here, we describe a multifunctional ultra-high vacuum instrument for conducting comprehensive studies of the adsorption, desorption, and surface chemistry of chemical warfare agents on model and militarily relevant surfaces. The system applies reflection-absorption infrared spectroscopy, x-ray photoelectron spectroscopy, and mass spectrometry to study adsorption and surface reactions of chemical warfare agents. Several novel components have been developed to address the unique safety and sample exposure challenges that accompany the research of these toxic, often very low vapor pressure, compounds. While results of vacuum-based surface science techniques may not necessarily translate directly to environmental processes, learning about the fundamental chemistry will begin to inform scientists about the critical aspects that impact real-world applications

Multifunctional ultra-high vacuum apparatus for studies of the interactions of chemical warfare agents on complex surfaces.

Science.gov (United States)

Wilmsmeyer, Amanda R; Gordon, Wesley O; Davis, Erin Durke; Mantooth, Brent A; Lalain, Teri A; Morris, John R

2014-01-01

A fundamental understanding of the surface chemistry of chemical warfare agents is needed to fully predict the interaction of these toxic molecules with militarily relevant materials, catalysts, and environmental surfaces. For example, rules for predicting the surface chemistry of agents can be applied to the creation of next generation decontaminants, reactive coatings, and protective materials for the warfighter. Here, we describe a multifunctional ultra-high vacuum instrument for conducting comprehensive studies of the adsorption, desorption, and surface chemistry of chemical warfare agents on model and militarily relevant surfaces. The system applies reflection-absorption infrared spectroscopy, x-ray photoelectron spectroscopy, and mass spectrometry to study adsorption and surface reactions of chemical warfare agents. Several novel components have been developed to address the unique safety and sample exposure challenges that accompany the research of these toxic, often very low vapor pressure, compounds. While results of vacuum-based surface science techniques may not necessarily translate directly to environmental processes, learning about the fundamental chemistry will begin to inform scientists about the critical aspects that impact real-world applications.

Multifunctional ultra-high vacuum apparatus for studies of the interactions of chemical warfare agents on complex surfaces

Energy Technology Data Exchange (ETDEWEB)

Wilmsmeyer, Amanda R.; Morris, John R. [Department of Chemistry, Virginia Tech, Blacksburg, Virginia 24061 (United States); Gordon, Wesley O.; Mantooth, Brent A.; Lalain, Teri A. [Research and Technology Directorate, U.S. Army Edgewood Chemical Biological Center, Aberdeen Proving Ground, Maryland 21010 (United States); Davis, Erin Durke [OptiMetrics, Inc., Abingdon, Maryland 21009 (United States)

2014-01-15

A fundamental understanding of the surface chemistry of chemical warfare agents is needed to fully predict the interaction of these toxic molecules with militarily relevant materials, catalysts, and environmental surfaces. For example, rules for predicting the surface chemistry of agents can be applied to the creation of next generation decontaminants, reactive coatings, and protective materials for the warfighter. Here, we describe a multifunctional ultra-high vacuum instrument for conducting comprehensive studies of the adsorption, desorption, and surface chemistry of chemical warfare agents on model and militarily relevant surfaces. The system applies reflection-absorption infrared spectroscopy, x-ray photoelectron spectroscopy, and mass spectrometry to study adsorption and surface reactions of chemical warfare agents. Several novel components have been developed to address the unique safety and sample exposure challenges that accompany the research of these toxic, often very low vapor pressure, compounds. While results of vacuum-based surface science techniques may not necessarily translate directly to environmental processes, learning about the fundamental chemistry will begin to inform scientists about the critical aspects that impact real-world applications.

Current and future challenges in the development of antimicrobial agents.

Science.gov (United States)

Rennie, Robert P

2012-01-01

Micro-organisms exist to survive. Even in the absence of antimicrobial agents, many have determinants of resistance that may be expressed phenotypically, should the need arise. With the advent of the antibiotic age, as more and more drugs were developed to treat serious infections, micro-organisms (particularly bacteria) rapidly developed resistance determinants to prevent their own demise.The most important determinants of resistance have been in the Gram-positive and Gram-negative bacteria. Among Gram-positive bacteria, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and penicillin-resistant Streptococcus pneumoniae (PRSP) have taxed researchers and pharmaceutical companies to develop new agents that are effective against these resistant strains. Among the Gram-negative bacteria, extended-spectrum beta-lactamase (ESBL) enzymes, carbapenemases (CREs) and the so-called amp-C enzymes that may be readily transferred between species of enterobacteriaceae and other facultative species have created multi-drug resistant organisms that are difficult to treat. Other resistance determinants have been seen in other clinically important bacterial species such as Neisseria gonorrhoeae, Clostridium difficile, Haemophilus influenzae and Mycobacterium tuberculosis. These issues have now spread to fungal agents of infection.A variety of modalities have been used to stem the tide of resistance. These include the development of niche compounds that target specific resistance determinants. Other approaches have been to find new targets for antimicrobial activity, use of combination agents that are effective against more than one target in the cell, or new delivery mechanism to maximize the concentration of antimicrobial agents at the site of infection without causing toxicity to the host. It is important that such new modalities have been proved effective for clinical therapy. Animal models and non-mammalian systems have been developed to

Natural products as radioprotective agents; past, present and future

International Nuclear Information System (INIS)

Baliga, Manjeshwar Shrinath

2013-01-01

The use of ionizing radiation, which is the cornerstone of cancer treatment, is compromised by the radiosensitivity of normal tissues. A chemical that can give selective benefit to the normal cells against the deleterious effects of ionizing radiation has been a long sought goal. However, most of the compounds studied have shown inadequate clinical application owing to their inherent toxicity, undesirable side effects, and high cost. Plants commonly used as dietary and or therapeutic agents have recently been the focus of attention since in most cases they are non-toxic and are easily accepted for human use. The proposed talk will mainly deal on the radioprotective potential of some important plant and herbal extracts. (author)

Radiographic scanning agent

International Nuclear Information System (INIS)

Bevan, J.A.

1983-01-01

The invention is on the water-soluble composition of matter selected from the group consisting of sup(99m)Tc-methanehydroxydiphosphonate, sup(99m)Tc-methanehydroxydiphosphonate-tin, sup(99m)Tc-methanehydroxydiphosphonate-iron, sup(99m)Tc-methanehydroxydiphosphonate-chromium and sup(99m)Tc-methanehydroxydiphosphonate-titanium. Another aspect of the invention is a process for preparing a water-soluble salt of methanehydroxydiphosphonic acid and a heavy metal selected from the group consisting of tin, iron, chromium and titanium, the heavy metal being in a reduced valence state. The process consists of reacting methanehydroxydiphosphonic acid or a water-soluble alkali metal, ammonium, alkylammonium, alkanolammonium salt or an ester of the acid which hydrolyses under use to the free acid or anion form of the acid, with a water-soluble salt of the heavy metal in a reduced valence state

Evaluating the Toxicity/Fixation Balance for Corneal Cross-Linking With Sodium Hydroxymethylglycinate (SMG) and Riboflavin-UVA (CXL) in an Ex Vivo Rabbit Model Using Confocal Laser Scanning Fluorescence Microscopy.

Science.gov (United States)

Kim, Su-Young; Babar, Natasha; Munteanu, Emilia Laura; Takaoka, Anna; Zyablitskaya, Mariya; Nagasaki, Takayuki; Trokel, Stephen L; Paik, David C

2016-04-01

To develop methods to delineate the relationship between endothelial cell toxicity and tissue fixation (toxicity/fixation) using sodium hydroxymethylglycinate (SMG), a formaldehyde releaser, and riboflavin-UVA photochemical corneal cross-linking (CXL) for therapeutic tissue cross-linking of the cornea. Eleven fresh cadaveric rabbit heads were used for ex vivo corneal cross-linking simulation. After epithelial debridement, the tissue was exposed to 1/4 max (9.8 mM) or 1/3 max (13 mM) SMG at pH 8.5 for 30 minutes or riboflavin-UVA (CXL). The contralateral cornea served as a paired control. Postexposure, cross-linking efficacy was determined by thermal denaturation temperature (Tm) and endothelial damage was assessed using calcein AM and ethidium homodimer staining (The Live/Dead Kit). Confocal laser scanning fluorescence microscopy was used to generate live/dead cell counts using a standardized algorithm. The ΔTm after CXL, 1/3 SMG, and 1/4 SMG was 2.2 ± 0.9°C, 1.3 ± 0.5°C, and 1.1 ± 0.5°C, respectively. Endothelial cell damage was expressed as the percent of dead cells/live + dead cells counted per high-power field. The values were 3 ± 1.7% (control) and 8.9 ± 11.1% (CXL) (P = 0.390); 1 ± 0.2% (control) and 19.5 ± 32.2% (1/3 max SMG) (P = 0.426); and 2.7 ± 2.4% (control) and 2.8 ± 2.2% (1/4 max SMG) (P = 0.938). The values for endothelial toxicity were then indexed over the shift in Tm to yield a toxicity/fixation index. The values were as follows: 2.7 for CXL, 14 for 1/3 max, and 0.1 for 1/4 max. Quarter max (1/4 max = 9.8 mM) SMG effectively cross-linked tissue and was nontoxic to endothelial cells. Thus, SMG is potentially a compound that could achieve both desired effects.

Genomic phenotyping by barcode sequencing broadly distinguishes between alkylating agents, oxidizing agents, and non-genotoxic agents, and reveals a role for aromatic amino acids in cellular recovery after quinone exposure.

Science.gov (United States)

Svensson, J Peter; Quirós Pesudo, Laia; McRee, Siobhan K; Adeleye, Yeyejide; Carmichael, Paul; Samson, Leona D

2013-01-01

Toxicity screening of compounds provides a means to identify compounds harmful for human health and the environment. Here, we further develop the technique of genomic phenotyping to improve throughput while maintaining specificity. We exposed cells to eight different compounds that rely on different modes of action: four genotoxic alkylating (methyl methanesulfonate (MMS), N-Methyl-N-nitrosourea (MNU), N,N'-bis(2-chloroethyl)-N-nitroso-urea (BCNU), N-ethylnitrosourea (ENU)), two oxidizing (2-methylnaphthalene-1,4-dione (menadione, MEN), benzene-1,4-diol (hydroquinone, HYQ)), and two non-genotoxic (methyl carbamate (MC) and dimethyl sulfoxide (DMSO)) compounds. A library of S. cerevisiae 4,852 deletion strains, each identifiable by a unique genetic 'barcode', were grown in competition; at different time points the ratio between the strains was assessed by quantitative high throughput 'barcode' sequencing. The method was validated by comparison to previous genomic phenotyping studies and 90% of the strains identified as MMS-sensitive here were also identified as MMS-sensitive in a much lower throughput solid agar screen. The data provide profiles of proteins and pathways needed for recovery after both genotoxic and non-genotoxic compounds. In addition, a novel role for aromatic amino acids in the recovery after treatment with oxidizing agents was suggested. The role of aromatic acids was further validated; the quinone subgroup of oxidizing agents were extremely toxic in cells where tryptophan biosynthesis was compromised.

Valorization of titanium metal wastes as tanning agent used in leather industry

Energy Technology Data Exchange (ETDEWEB)

Crudu, Marian, E-mail: mariancrudu@yahoo.com [The National Research and Development Institute for Textiles and Leather – Division Leather and Footwear Research Institute, 93 Ion Minulescu Str., Bucharest (Romania); Deselnicu, Viorica, E-mail: viorica.deselnicu@icpi.ro [The National Research and Development Institute for Textiles and Leather – Division Leather and Footwear Research Institute, 93 Ion Minulescu Str., Bucharest (Romania); Deselnicu, Dana Corina, E-mail: d_deselnicu@yahoo.com [University Politehnica Bucharest, Splaiul Independentei Nr. 313, Sector 6, RO-060042 Bucharest (Romania); Albu, Luminita, E-mail: luminita.albu@gmail.com [The National Research and Development Institute for Textiles and Leather – Division Leather and Footwear Research Institute, 93 Ion Minulescu Str., Bucharest (Romania)

2014-10-15

Highlights: • Valorization of titanium wastes which cannot be recycled in metallurgical industry. • Transferring Ti waste into raw materials for obtaining Ti based tanning agent. • Characterization of new Ti based tanning agents and leather tanned with them. • Characterization of sewage waste water and sludge resulted from leather manufacture. • Analysis of the impact of main metal component of Ti waste. - Abstract: The development of new tanning agents and new technologies in the leather sector is required to cope with the increasingly higher environmental pressure on the current tanning materials and processes such as tanning with chromium salts. In this paper, the use of titanium wastes (cuttings) resulting from the process of obtaining highly pure titanium (ingots), for the synthesis of new tanning agent and tanning bovine hides with new tanning agent, as alternative to tanning with chromium salts are investigated. For this purpose, Ti waste and Ti-based tanning agent were characterized for metal content by inductively coupled plasma mass spectrometry (ICP-MS) and chemical analysis; the tanned leather (wet white leather) was characterized by Scanning Electron Microscope/Energy Dispersive Using X-ray (Analysis). SEM/EDX analysis for metal content; Differential scanning calorimetric (DSC), Micro-Hot-Table and standard shrinkage temperature showing a hydrothermal stability (ranged from 75.3 to 77 °C) and chemical analysis showing the leather is tanned and can be processed through the subsequent mechanical operations (splitting, shaving). On the other hand, an analysis of major minor trace substances from Ti-end waste (especially vanadium content) in new tanning agent and wet white leather (not detected) and residue stream was performed and showed that leachability of vanadium is acceptable. The results obtained show that new tanning agent obtained from Ti end waste can be used for tanning bovine hides, as eco-friendly alternative for chrome tanning.

Valorization of titanium metal wastes as tanning agent used in leather industry

International Nuclear Information System (INIS)

Crudu, Marian; Deselnicu, Viorica; Deselnicu, Dana Corina; Albu, Luminita

2014-01-01

Highlights: • Valorization of titanium wastes which cannot be recycled in metallurgical industry. • Transferring Ti waste into raw materials for obtaining Ti based tanning agent. • Characterization of new Ti based tanning agents and leather tanned with them. • Characterization of sewage waste water and sludge resulted from leather manufacture. • Analysis of the impact of main metal component of Ti waste. - Abstract: The development of new tanning agents and new technologies in the leather sector is required to cope with the increasingly higher environmental pressure on the current tanning materials and processes such as tanning with chromium salts. In this paper, the use of titanium wastes (cuttings) resulting from the process of obtaining highly pure titanium (ingots), for the synthesis of new tanning agent and tanning bovine hides with new tanning agent, as alternative to tanning with chromium salts are investigated. For this purpose, Ti waste and Ti-based tanning agent were characterized for metal content by inductively coupled plasma mass spectrometry (ICP-MS) and chemical analysis; the tanned leather (wet white leather) was characterized by Scanning Electron Microscope/Energy Dispersive Using X-ray (Analysis). SEM/EDX analysis for metal content; Differential scanning calorimetric (DSC), Micro-Hot-Table and standard shrinkage temperature showing a hydrothermal stability (ranged from 75.3 to 77 °C) and chemical analysis showing the leather is tanned and can be processed through the subsequent mechanical operations (splitting, shaving). On the other hand, an analysis of major minor trace substances from Ti-end waste (especially vanadium content) in new tanning agent and wet white leather (not detected) and residue stream was performed and showed that leachability of vanadium is acceptable. The results obtained show that new tanning agent obtained from Ti end waste can be used for tanning bovine hides, as eco-friendly alternative for chrome tanning

Toxicity of road salt to Nova Scotia amphibians

International Nuclear Information System (INIS)

Collins, Sara J.; Russell, Ronald W.

2009-01-01

The deposition of chemical pollutants into roadside wetlands from runoff is a current environmental concern. In northern latitudes, a major pollutant in runoff water is salt (NaCl), used as de-icing agents. In this study, 26 roadside ponds were surveyed for amphibian species richness and chloride concentration. Acute toxicity tests (LC 50 ) were performed on five locally common amphibian species using a range of environmentally significant NaCl concentrations. Field surveys indicated that spotted salamanders (Ambystoma maculatum) and wood frogs (Rana sylvatica) did not occupy high chloride ponds. American toads (Bufo americanus) showed no pond preference based on chloride concentration. Acute toxicity tests showed spotted salamanders and wood frogs were most sensitive to chloride, and American toads were the least. Spring peepers (Pseudacris crucifer) and green frogs (Rana clamitans) showed intermediate sensitivities. We concluded that chloride concentrations in ponds due to application of de-icing salts, influenced community structure by excluding salt intolerant species. - Salt toxicity is presented as a mechanism affecting the distribution of amphibians and structure of amphibian communities in roadside wetlands

Boron Toxicity Causes Multiple Effects on Malus domestica Pollen Tube Growth.

Science.gov (United States)

Fang, Kefeng; Zhang, Weiwei; Xing, Yu; Zhang, Qing; Yang, Liu; Cao, Qingqin; Qin, Ling

2016-01-01

Boron is an important micronutrient for plants. However, boron is also toxic to cells at high concentrations, although the mechanism of this toxicity is not known. This study aimed to evaluate the effect of boron toxicity on Malus domestica pollen tube growth and its possible regulatory pathway. Our results showed that a high concentration of boron inhibited pollen germination and tube growth and led to the morphological abnormality of pollen tubes. Fluorescent labeling coupled with a scanning ion-selective electrode technique detected that boron toxicity could decrease [Ca(2+)]c and induce the disappearance of the [Ca(2+)]c gradient, which are critical for pollen tube polar growth. Actin filaments were therefore altered by boron toxicity. Immuno-localization and fluorescence labeling, together with fourier-transform infrared analysis, suggested that boron toxicity influenced the accumulation and distribution of callose, de-esterified pectins, esterified pectins, and arabinogalactan proteins in pollen tubes. All of the above results provide new insights into the regulatory role of boron in pollen tube development. In summary, boron likely plays a structural and regulatory role in relation to [Ca(2+)]c, actin cytoskeleton and cell wall components and thus regulates Malus domestica pollen germination and tube polar growth.

Comparison of gadolinium Cy2DOTA, a new hepatobiliary agent, and gadolinium HP-DO3A, an extracellular agent, in healthy liver and metastatic disease

International Nuclear Information System (INIS)

Runge, V.M.; Wells, J.W.; Williams, N.M.

1995-01-01

A new gadolinium (Gd) chelate with preferential hepatobiliary uptake, Gd Cy 2 DOTA, was compared in two animal species with Gd HP-DO3A (gadoteridol), a clinically approved contrast agent with extracellular distribution. Liver enhancement was evaluated for these two contrast agents using magnetic resonance imaging, whereas an experimental model of metastatic disease was used to evaluate the agents' efficacy for liver-lesion delineation. The two agents were compared in four healthy Rhesus monkeys (eight studies) and five New Zealand White rabbits with implanted VX-2 liver tumors (ten studies). The contrast dose was 0.1 mmol/kg, with the agents given in random order and at least 72 hours between contrast injections. Breathhold T1-weighted spin echo scans were obtained at 1.5 tesla (T) before and after contrast was administered. Postcontrast scans were obtained 1 to 90 minutes after injection in the monkeys and 1 to 240 minutes after injection in the rabbits. Prolonged hepatic enhancement, superior in degree to that with Gd HP-DO3A, was noted to both monkeys and rabbits after injection of Gd Cy 2 DOTA. Two minutes after contrast, liver SI was 1.94 ± 0.05 with Gd Cy 2 DOTA compared with 1.5 ± 0.05 with Gd HP-DO3A in monkeys. Sixty minutes after contrast, liver SI was 1.60 ± 0.09 compared with 1.20 ± 0.02. The difference between agents was significant at all times from 2 to 60 minutes after contrast injection (P 2 DOTA but not with Gd HP-DO3A. The maximum improvement in lesion conspicuity (rabbit) occurred 45 minutes after injection of Gd Cy 2 DOTA and 5 minutes after injection of Gd HP-DO3A. 22 refs., 12 figs

Destruction of chlorine-containing organic agents in a system plasma - liquid

International Nuclear Information System (INIS)

Chernyak, V.Ya.; Yukhymenko, V.V.; Babich, I.L.; Slyusarenko, Y.I.; Tarasova, Ya.B.

2005-01-01

The plasma chemical destruction of persistent toxic agent 1,1-di(4-chlorophenol)-2,2,2-threechlorethane (DDT) in water solutions is researched in this work. The destruction of agricultural pesticide containing DDT was carried out in water solution at atmospheric pressure with usage of plasma treatment on the basis of secondary discharges with a 'liquid' electrode, and of combination of a plasma method with reagent method. The comparative analysis of results of the physical-chemical analysis and biological test of toxicity of solutions is carried out and the optimum regimes for destruction and detoxication of DDT in water are determined

Where does the toxicity come from in saponin extract?

Science.gov (United States)

Jiang, Xiaogang; Cao, Yi; Jørgensen, Louise von Gersdorff; Strobel, Bjarne W; Hansen, Hans Chr Bruun; Cedergreen, Nina

2018-08-01

Saponin-rich plant extracts contain bioactive natural compounds and have many applications, e.g. as biopesticides and biosurfactants. The composition of saponin-rich plant extracts is very diverse, making environmental monitoring difficult. In this study various ecotoxicity data as well as exposure data have been collected to explore which compounds in the plant extract are relevant as plant protection agents and furthermore to clarify which compounds may cause undesired side-effects due to their toxicity. Hence, we quantified the toxicity of different fractions (saponins/non-saponins) in the plant extracts on the aquatic crustacean Daphnia magna and zebrafish (Danio rerio) embryos. In addition, we tested the toxicity changes during saponin degradation as well. The results confirm that saponins are responsible for the majority of toxicity (85.1-93.6%) of Quillaja saponaria extract. We, therefore, suggest saponins to be the main target of saponin-rich plant extracts, for instance in the saponin-based biopesticide regulation. Furthermore, we suggest that an abundant saponin fraction, QS-18 from Q. saponaria, can be a key monitoring target to represent the environmental concentration of the saponins, as it contributes with 26% and 61% of the joint toxicity to D. magna and D. rerio, respectively out of the total saponins. The degradation products of saponins are 3-7 times less toxic than the parent compound; therefore the focus should be mainly on the parent compounds. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Study and Development of Metal Oxide Reactive Adsorbents for the Destruction of Toxic Organic Compounds

National Research Council Canada - National Science Library

Mitchell, Mark B

2008-01-01

... and other toxic organic compounds. The research program that was developed built upon earlier results achieved in the room temperature oxidative decomposition of a chemical warfare agent simulant, dimethyl methylphosphonate (DMMP...

Examining multi-component DNA-templated nanostructures as imaging agents

Science.gov (United States)

Jaganathan, Hamsa

2011-12-01

Magnetic resonance imaging (MRI) is the leading non-invasive tool for disease imaging and diagnosis. Although MRI exhibits high spatial resolution for anatomical features, the contrast resolution is low. Imaging agents serve as an aid to distinguish different types of tissues within images. Gadolinium chelates, which are considered first generation designs, can be toxic to health, while ultra-small, superparamagnetic nanoparticles (NPs) have low tissue-targeting efficiency and rapid bio-distribution, resulting to an inadequate detection of the MRI signal and enhancement of image contrast. In order to improve the utility of MRI agents, the challenge in composition and structure needs to be addressed. One-dimensional (1D), superparamagnetic nanostructures have been reported to enhance magnetic and in vivo properties and therefore has a potential to improve contrast enhancement in MRI images. In this dissertation, the structure of 1D, multi-component NP chains, scaffolded on DNA, were pre-clinically examined as potential MRI agents. First, research was focused on characterizing and understanding the mechanism of proton relaxation for DNA-templated NP chains using nuclear magnetic resonance (NMR) spectrometry. Proton relaxation and transverse relaxivity were higher in multi-component NP chains compared to disperse NPs, indicating the arrangement of NPs on a 1D structure improved proton relaxation sensitivity. Second, in vitro evaluation for potential issues in toxicity and contrast efficiency in tissue environments using a 3 Tesla clinical MRI scanner was performed. Cell uptake of DNA-templated NP chains was enhanced after encapsulating the nanostructure with layers of polyelectrolytes and targeting ligands. Compared to dispersed NPs, DNA-templated NP chains improved MRI contrast in both the epithelial basement membrane and colon cancer tumors scaffolds. The last part of the project was focused on developing a novel MRI agent that detects changes in DNA methylation

Characterization of nanoparticle-based contrast agents for molecular magnetic resonance imaging

International Nuclear Information System (INIS)

Shan, Liang; Chopra, Arvind; Leung, Kam; Eckelman, William C.; Menkens, Anne E.

2012-01-01

The development of molecular imaging agents is currently undergoing a dramatic expansion. As of October 2011, ∼4,800 newly developed agents have been synthesized and characterized in vitro and in animal models of human disease. Despite this rapid progress, the transfer of these agents to clinical practice is rather slow. To address this issue, the National Institutes of Health launched the Molecular Imaging and Contrast Agents Database (MICAD) in 2005 to provide freely accessible online information regarding molecular imaging probes and contrast agents for the imaging community. While compiling information regarding imaging agents published in peer-reviewed journals, the MICAD editors have observed that some important information regarding the characterization of a contrast agent is not consistently reported. This makes it difficult for investigators to evaluate and meta-analyze data generated from different studies of imaging agents, especially for the agents based on nanoparticles. This article is intended to serve as a guideline for new investigators for the characterization of preclinical studies performed with nanoparticle-based MRI contrast agents. The common characterization parameters are summarized into seven categories: contrast agent designation, physicochemical properties, magnetic properties, in vitro studies, animal studies, MRI studies, and toxicity. Although no single set of parameters is suitable to define the properties of the various types of contrast agents, it is essential to ensure that these agents meet certain quality control parameters at the preclinical stage, so that they can be used without delay for clinical studies.

Effect of nano silica based modifying agent for hydrophobic coating application

International Nuclear Information System (INIS)

Nurul Huda Mudri; Nik Ghazali Nik Salleh; Mek Zah Salleh

2016-01-01

Hydrophobic coatings find wide application in industry due to their unique features such as water repellent and self-cleaning properties. In this study, modifying agent was synthesized by way of nano silica particles dispersion in polydimethyl siloxane with addition of surfactant, catalyst and stabilizer using high speed distemper. The modifying agent was added into coating formulation and cured under UV exposure. Scanning Electron Microscopy image of the film found that the nano silica particles were distributed well on substrate. Contact angle measurement gave the highest reading of 116 degree for 20 % wt of the modifying agent. The optical properties of the film were evaluated via transmission and haze test. (author)

Time-resolved studies define the nature of toxic IAPP intermediates, providing insight for anti-amyloidosis therapeutics

Science.gov (United States)

Abedini, Andisheh; Plesner, Annette; Cao, Ping; Ridgway, Zachary; Zhang, Jinghua; Tu, Ling-Hsien; Middleton, Chris T; Chao, Brian; Sartori, Daniel J; Meng, Fanling; Wang, Hui; Wong, Amy G; Zanni, Martin T; Verchere, C Bruce; Raleigh, Daniel P; Schmidt, Ann Marie

2016-01-01

Islet amyloidosis by IAPP contributes to pancreatic β-cell death in diabetes, but the nature of toxic IAPP species remains elusive. Using concurrent time-resolved biophysical and biological measurements, we define the toxic species produced during IAPP amyloid formation and link their properties to induction of rat INS-1 β-cell and murine islet toxicity. These globally flexible, low order oligomers upregulate pro-inflammatory markers and induce reactive oxygen species. They do not bind 1-anilnonaphthalene-8-sulphonic acid and lack extensive β-sheet structure. Aromatic interactions modulate, but are not required for toxicity. Not all IAPP oligomers are toxic; toxicity depends on their partially structured conformational states. Some anti-amyloid agents paradoxically prolong cytotoxicity by prolonging the lifetime of the toxic species. The data highlight the distinguishing properties of toxic IAPP oligomers and the common features that they share with toxic species reported for other amyloidogenic polypeptides, providing information for rational drug design to treat IAPP induced β-cell death. DOI: http://dx.doi.org/10.7554/eLife.12977.001 PMID:27213520

Toxicity studies of drugs and chemicals in animals: An overview

Directory of Open Access Journals (Sweden)

S. Saganuwan

2017-12-01

Full Text Available Toxicity study is the investigation of either short or long-term toxic effects of a drug or chemical on animals. The toxicity is dose-dependent as asserted by Paracelsus over 500 years ago. However, short-term toxic effect is determined using median lethal dose (LD50 first introduced by Trevan in 1927 and revised many times. Presently there is a growing preponderance of rejection of scientific papers on acute toxicity study, simply because of the belief that in the current hazard and safety as-sessment of drugs and chemicals, LD50 values are no longer used. In view of this, literature search was carried out with a view to investigating the relevance of LD50 in development and assessment of drugs and chemicals. The findings revealed that in the past, many animals had been used for LD50 determination. OECD has reduced the number of test animals to 5–15 and presently it is further re-duced to 2–6. Acute toxicity study is being carried out in medicinal plants research and in the study of patent medicine. Although the application of LD50 has been drastically reduced, it is still applied and accepted in some parts of the world. Moreover, animals on which LD50 tests are conducted, should be allowed to die to see the end effect of the test drug or chemical because euthanisia of test animals may mask some toxicity signs of the test agents. Therefore, toxicity study of drugs and chemicals is a sci-entific process necessary for discovery and development of drugs as well as identification of potential toxicants.

Accounting for dissociation and photolysis: a review of the algal toxicity of triclosan.

Science.gov (United States)

Roberts, Jayne; Price, Oliver R; Bettles, Nicola; Rendal, Cecilie; van Egmond, Roger

2014-11-01

Triclosan, an antimicrobial agent commonly used in down-the-drain consumer products, is toxic to freshwater microalgae. However, the rapid photolysis and pH-dependent dissociation of this compound may give rise to uncertainty in growth inhibition tests with freshwater microalgae, if these are not well characterized. Methods are presented to minimize these uncertainties by stabilizing pH with an organic buffering agent (Bis-Tris) and by the application of ultraviolet (UV) covers to remove UV wavelengths. Toxicity tests with these methods were in compliance with the validity criteria of the Organisation for Economic Co-operation and Development test 201, and no negative effects were seen in controls relative to the unmodified method. The methods were used for toxicity tests with triclosan at pH levels of 7.0, 8.0, and 8.5, yielding effective concentration, 10% values of 0.5 µg/L, 0.6 µg/L, and 12.1 µg/L, respectively. The observed change in toxicity with pH was proportional to the change in bioconcentration factor (BCF) as calculated using the cell model (a dynamic flux model based on the Fick-Nernst-Planck equations, in this case parameterized for an algal cell). Effect concentrations produced with the methods presented in the present study offer robust data on which to base risk assessment, and it is suggested that similar approaches be used to minimize uncertainty when other compounds that dissociate and photolyse are tested. © 2014 SETAC.

Effects of Humic and Fulvic Acids on Silver Nanoparticle Stability, Dissolution, and Toxicity

Science.gov (United States)

Gunsolus, Ian L.; Mousavi, Maral P. S.; Hussein, Kadir; Bühlmann, Philippe; Haynes, Christy L.

2015-01-01

The colloidal stability of silver nanoparticles (AgNPs) in natural aquatic environments influences their transport and environmental persistence, while their dissolution to Ag+ influences their toxicity to organisms. Here, we characterize the colloidal stability, dissolution behavior, and toxicity of two industrially relevant classes of AgNPs (i.e., AgNPs stabilized by citrate or polyvinylpyrrolidone) after exposure to natural organic matter (NOM, i.e., Suwannee River Humic and Fulvic Acid Standards and Pony Lake Fulvic Acid Reference). We show that NOM interaction with the nanoparticle surface depends on (i) the NOM’s chemical composition, where sulfur- and nitrogen-rich NOM more significantly increases colloidal stability, and (ii) the affinity of the capping agent for the AgNP surface, where nanoparticles with loosely bound capping agents are more effectively stabilized by NOM. Adsorption of NOM is shown to have little effect on AgNP dissolution under most experimental conditions, the exception being when the NOM is rich in sulfur and nitrogen. Similarly, the toxicity of AgNPs to a bacterial model (Shewanella oneidensis MR-1) decreases most significantly in the presence of sulfur- and nitrogen-rich NOM. Our data suggest that the rate of AgNP aggregation and dissolution in aquatic environments containing NOM will depend on the chemical composition of the NOM, and that the toxicity of AgNPs to aquatic microorganisms is controlled primarily by the extent of nanoparticle dissolution. PMID:26047330

90Y Colchicine: an attempt to prepare a tumor radiotherapeutic agent

International Nuclear Information System (INIS)

Korde, Aruna; Satpati, Drishty; Pandey, Usha; Banerjee, Sharmila; Venkatesh, Meera

2006-01-01

Colchicine, an alkaloid occurring in the seeds of the plant Colchicum autumnale has been used for the treatment of acute gout. Colchicine binds to microtubules and exhibits antimitotic action in dividing cells. Various structural modifications of colchicine moiety have been studied with an aim to identify an antineoplastic agent with reduced toxicity

Evaluation of Fluorine-18 as a Scanning Agent for Intracranial Tumours; Emploi du Fluor-18 en Scintigraphy des Tumeurs Intracraniennes; Otsenka Ftora-18 kak skenniruyushchego agenta dlya vnutricherepnykh opukholej; Examen de las Caracteristicas del Fluor-18 como Agente de Exploracion de los Tumores Intracraneales

Energy Technology Data Exchange (ETDEWEB)

Entzian, W.; Aronow, S.; Soloway, A. H.; Sweet, W. H. [Massachusetts General Hospital, Boston, MA (United States)

1964-10-15

F{sup 18}, a 110-min half-life, positron emitter was studied as a possible agent for brain-tumour localization. It was prepared in a nuclear reactor by thermal neutron irradiation of Li{sub 2}CO{sub 3} (Li{sup 6} (n, {alpha}) H{sup 3}, O{sup 16}(H{sup 3}, n) F{sup 18}). Tissue studies in mice bearing subcutaneously-transplanted ependymomas indicated that labelled sodium fluoride (NaF{sup 18}) gave excessive concentrations in bone and was therefore unsuitable as a brain-scanning agent. However, labelled potassium fluoborate (KBF{sup 18}{sub 4}) showed good preferential uptake in tumour compared with brain, uptake ratios ranging from 8 to 11. No excessive concentrations were found in other organs in either mice or cats. Toxicity studies were carried out in mice and rabbits at levels of 300 mg/kg and 120 mgAg respectively. No adverse effects were observed provided the solution was neutralized to a physiological pH. The chemical amounts needed for patient scanning were less than 0.5 mgAg of body weight. A comparative clinical study of 10 patients, each scanned with KBF{sup 18}{sub 4} and other isotopic agents, corroborated the findings of Askenasy et al. that this is a useful compound for brain-tumour localization. Intravenous injection was optimally performed 30 min before scanning at a dosage of 15 {mu}c/kg of body weight. Tissue samples of tumour and normal brain were obtained from one patient at operation. The uptake ratio was 3.5. While this is lower than that found in the mouse, it is still in a useful range. Blood samples obtained from patients at varying time intervals after injection yielded a blood clearance curve which had two time constants. The first was very rapid and the second slower. This sequence is typical of useful scanning agents. (author) [French] Les auteurs ont etudie la possibilite d'employer {sup 18}F, emetteur de positons ayant une periode de 110 min, pour localiser lcs tumeurs du cerveau. Cette substance a ete preparee dans un reacteur par

Metabolic acidosis in an infant associated with permethrin toxicity.

Science.gov (United States)

Goksugur, Sevil B; Karatas, Zehra; Goksugur, Nadir; Bekdas, Mervan; Demircioglu, Fatih

2015-01-01

Pyrethroids are broad-spectrum insecticides. Permethrin intoxication due to topical application has not been documented in humans. We report a 20-month-old infant who had used 5% permethrin lotion topically for scabies treatment. Approximately 60 mL (20 mL/day) was used and after the third application he developed agitation, nausea, vomiting, respiratory distress, tachycardia, and metabolic acidosis. His clinical symptoms and metabolic acidosis normalized within 20 hours. His follow-up was unremarkable. Toxicity of permethrin is rare, and although permethrin is a widely and safely used topical agent in the treatment of scabies and lice, inappropriate use may rarely cause toxicity. Moreover, in cases of unexplained metabolic acidosis, topically applied medications should be carefully investigated. © 2014 Wiley Periodicals, Inc.

Multifrequency scanning probe microscopy study of nanodiamond agglomerates

Science.gov (United States)

Aravind, Vasudeva; Lippold, Stephen; Li, Qian; Strelcov, Evgheny; Okatan, Baris; Legum, Benjamin; Kalinin, Sergei; Clarion University Team; Oak Ridge National Laboratory Team

Due to their rich surface chemistry and excellent mechanical properties and non-toxic nature, nanodiamond particles have found applications such as biomedicine, tribology and lubrication, targeted drug delivery systems, tissue scaffolds and surgical implants. Although single nanodiamond particles have diameters about 4-5nm, they tend to form agglomerates. While these agglomerates can be useful for some purposes, many applications of nanodiamonds require single particle, disaggregated nanodiamonds. This work is oriented towards studying forces and interactions that contribute to agglomeration in nanodiamonds. In this work, using multifrequency scanning probe microscopy techniques, we show that agglomerate sizes can vary between 50-100nm in raw nanodiamonds. Extremeties of particles and Interfaces between agglomerates show dissipative forces with scanning probe microscope tip, indicating agglomerates could act as points of increased adhesion, thus reducing lubricating efficiency when nanodiamonds are used as lubricant additives. This research was conducted at the Center for Nanophase Materials Sciences, which is a DOE Office of Science User Facility.

Investigation of sewage sludge gasification with use of flue gas as a gasifying agent

Directory of Open Access Journals (Sweden)

Maj Izabella

2017-01-01

Full Text Available The paper presents results of investigation of low-temperature sewage sludge gasification with use of flue gas as a gasifying agent. Tests were conducted in a laboratory stand, equipped with a gasification reactor designed and constructed specifically for this purpose. During presented tests, gas mixture with a composition of typical flue gases was used as a gasifying agent. The measuring system ensures online measurements of syngas composition: CO, CO2, H2, CH4. As a result of gasification process a syngas with combustible components has been obtained. The aim of the research was to determine the usability of sewage sludge for indirect cofiring in power boilers with the use of flue gas from the boiler as a gasifying agent and recirculating the syngas to the boiler’s combustion chamber. Results of presented investigation will be used as a knowledge base for industrial-scale sewage sludge gasification process. Furthermore, toxicity of solid products of the process has been determined by the use of Microtox bioassay. Before tests, solid post-gasification residues have been ground to two particle size fractions and extracted into Milli-Q water. The response of test organisms (bioluminescent Aliivibrio fischeri bacteria in reference to a control sample (bacteria exposed to 2% NaCl solution was measured after 5 and 15 minutes of exposure. The obtained toxicity results proved that thermal treatment of sewage sludge by their gasification reduces their toxicity relative to water organisms.

Acute ecological toxicity and environmental persistence of simulants

Energy Technology Data Exchange (ETDEWEB)

Cataldo, D.A.; Ligotke, M.W.; McVeety, B.D.; Fellows, R.J.; Bolton, H. Jr.; Li, S.W.; Van Voris, P.; Wentsel, R.S.

1988-06-01

The objectives of these studies are to establish the comparative environmental behavior and chemical fate of chemical simulants. Laboratory studies were undertaken to establish: (1) deposition efficiency (deposition velocities, Vd) for receptor surfaces including plant foliage and soils; (2) dose/response relationships for important environmental components including plants and soil microflora; and (3) the environmental persistence of the simulants. Chemical agent simulants are employed for a range of testing and training activities where use of chemical agents is less than suitable from a safety and environmental standpoint. A variety of chemical simulant materials are used to simulate either nerve agents or blister agents. The following research describes the environmental effects and persistence of four simulants. These are the nerve agent stimulants diisopropyl methylphosphonate (DIMP), diisopropyl fluorophosphate (DFP), and bis (2-ethylhexyl) phosphonate (BIS), and the mustard stimulant 2-chloroethyl ethyl sulfide (CEES). The vapor pressures for DIMP, DFP, and CEES are relatively high, reported to be 0.17, 0.58 and 3.4 mm Hg, respectively; while that of BIS is substantially less at 5.8 /times/ 10/sup /minus/5/ mm Hg at 25/degree/C. The chemical characteristics of DFP and CEES are very similar to G/VX-agents and mustard, respectively, and are employed for materials evaluation under controlled conditions. However, their toxicity precludes their use in the environment. DIMP and BIS are currently used for testing in the open air. 3 figs., 3 tabs.

Targeting property and toxicity of a novel ultrasound contrast agent microbubble carrying the targeting and drug-loaded complex FA-CNTs-PTX on MCF7 cells.

Science.gov (United States)

Zhang, Jie; Zhang, Yu; Liu, Junxi; Li, Guozhong; Wen, Zhaohui; Zhao, Yue; Zhang, Xiangyu; Liu, Fenghua

2017-10-01

The application of ultrasound contrast agents not only is confined to the enhancement of ultrasound imaging but also has started to be used as a drug system for diagnosis and treatment. In this paper, Span60 and PEG1500 were used as membrane materials, and a new targeting and drug-loading multifunctional ultrasound contrast agent microbubble enveloping the FA-CNTs-PTX complex was successfully prepared by acoustic cavitation. With the breast cancer cell line MCF7 as the research target, the effects of the microbubble with FA-CNTs-PTX on the proliferation and toxicity of MCF7 cells were studied using a CCK-8 and AO/EB double-staining method. The influences of the microbubbles with FA-CNTs-PTX on the cellular morphology and apoptosis period of the MCF7 cells were detected using an inverted fluorescence microscope. The apoptosis of MCF7 cells induced by the microbubbles with FA-CNTs-PTX was investigated with flow cytometry and an annexin and PI double staining fluorescence quantitative analysis. The results indicated that the ultrasound contrast agent microbubble with FA-CNTs-PTX remarkably inhibited the proliferation of MCF7 cells, which was mainly controlled by the drug loading rate and the nanometer size of the microbubbles. Moreover, the proliferative inhibition rate of the microbubbles with FA-CNTs-PTX was related to the cell apoptosis period of MCF7 cells. Its inhibition degree on the proliferation of MCF7 cells was higher than that of the hepatoma HepG2 cells. The apoptosis rate of MCF7 cells induced by the microbubbles with FA-CNTs-PTX was higher than that of normal human umbilical vein endothelial cells (HUVECs), and the microbubbles with FA-CNTs-PTX could target the MCF7 cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Influence of genetic variants on toxicity to anti-tubercular agents: a systematic review and meta-analysis (protocol).

Science.gov (United States)

Richardson, Marty; Kirkham, Jamie; Dwan, Kerry; Sloan, Derek; Davies, Geraint; Jorgensen, Andrea

2017-07-13

Tuberculosis patients receiving anti-tuberculosis treatment may experience serious adverse drug reactions, such as hepatotoxicity. Genetic risk factors, such as polymorphisms of the NAT2, CYP2E1 and GSTM1 genes, may increase the risk of experiencing such toxicity events. Many pharmacogenetic studies have investigated the association between genetic variants and anti-tuberculosis drug-related toxicity events, and several meta-analyses have synthesised data from these studies, although conclusions from these meta-analyses are conflicting. Many meta-analyses also have serious methodological limitations, such as applying restrictive inclusion criteria, or not assessing the quality of included studies. Most also only consider hepatotoxicity outcomes and specific genetic variants. The purpose of this systematic review and meta-analysis is to give a comprehensive evaluation of the evidence base for associations between any genetic variant and anti-tuberculosis drug-related toxicity. We will search for studies in MEDLINE, EMBASE, BIOSIS and Web of Science. We will also hand search reference lists from relevant studies and contact experts in the field. We will include cohort studies, case-control studies and randomised controlled trials that recruited patients with tuberculosis who were either already established on anti-tuberculosis treatment or were commencing treatment and who were genotyped to investigate the effect of genetic variants on any anti-tuberculosis drug-related toxicity outcome. One author will screen abstracts to identify potentially relevant studies and will then obtain the full text for each potentially relevant study in order to assess eligibility. At each of these stages, a second author will independently screen/assess 10% of studies. Two authors will independently extract data and assess the quality of studies using a pre-piloted data extraction form. If appropriate, we will pool estimates of effect for each genotype on each outcome using meta

Uncommon toxicity of low-dose methotrexate: case report

Directory of Open Access Journals (Sweden)

Zohreh Yousefi

2015-10-01

Full Text Available Background: Standard treatment of Gestational Trophoblastic Disease (GTD is chemotherapy. Single-agent chemotherapy regime including Methotrexate (MTX or Actinomycin. Single-agent is widely used in treatment of persistent trophoblastic disease. We reported an uncommon toxicity of low-dose single-agent methotrexate in a patient. Case Presentation: A 20-year-old woman, primary gravid after two months missed period and spotting with diagnosis of incomplete abortion with uterine size equivalent of ten weeks pregnancy (8-10 cm underwent evacuation curettage. In serial follow-up, based on rise of beta-hCG titer and absence of metastatic disease, it was categorized as low-risk persistent trophoblastic disease. She was referred to gynecology oncology center of Ghaem Hospital, Mashhad University of Medical Sciences in May 2014. Because of rise of beta-hCG titer, after complete metastatic work-up and lack of disease in other sites, persistent disease was diagnosed and candidate for chemotherapy (single agent low-dose. The patient received first course of therapy with MTX (50 mg/m², intra muscular. Unfortunately, after two days of treatment she developed uncommon severe toxicity, fever, severe nausea and vomiting, tachycardia, and generalized weakness. Also, we found hematologic abnormality (WBC: -14000-15000 µI, platelet- 540 µI and sever neutropenia, and abnormal rising in liver function test (SGOT, SGPT (three to four times and renal function test (BUN and Creatinine (two times. In addition, she had disseminated erosive lesion in all of body especially in face. Due to the fatal side effects of chemotherapy, she was admitted to intensive care unit (ICU. Fortunately, after two to three weeks, she was improved by conservative management. After few weeks beta-hCG titer was in normal limit. However she had normal serial beta-hCG in one year of follow-up. Conclusion: It is important to emphasis unpredictable side effects of chemotherapy with low

A Potential Adjuvant Agent of Chemotherapy: Sepia Ink Polysaccharides

Directory of Open Access Journals (Sweden)

Fangping Li

2018-03-01

Full Text Available Sepia ink polysaccharide (SIP isolated from squid and cuttlefish ink is a kind of acid mucopolysaccharide that has been identified in three types of primary structures from squid (Illex argentinus and Ommastrephes bartrami, cuttlefish Sepiella maindroni, and cuttlefish Sepia esculenta ink. Although SIP has been proved to be multifaceted, most of the reported evidence has illuminated its chemopreventive and antineoplastic activities. As a natural product playing a role in cancer treatment, SIP may be used as chemotherapeutic ancillary agent or functional food. Based on the current findings on SIP, we have summarized four topics in this review, including: chemopreventive, antineoplastic, chemosensitive, and procoagulant and anticoagulant activities, which are correlative closely with the actions of anticancer agents on cancer patients, such as anticancer, toxicity and thrombogenesis, with the latter two actions being common causes of death in cancer cases exposed to chemotherapeutic agents.

Dextromethorphan, chlorphenamine and serotonin toxicity: case report and systematic literature review

Science.gov (United States)

Monte, Andrew A; Chuang, Ryan; Bodmer, Michael

2010-01-01

The aim of this review was to describe a patient with serotonin toxicity after an overdose of dextromethorphan and chlorphenamine and to perform a systematic literature review exploring whether dextromethorphan and chlorphenamine may be equally contributory in the development of serotonin toxicity in overdose. A Medline literature review was undertaken to identify cases of serotonin toxicity due to dextromethorphan and/or chlorphenamine. Case reports were included if they included information on the ingested dose or plasma concentrations of dextromethorphan and/or chlorphenamine, information about co-ingestions and detailed clinical information to evaluate for serotonin toxicity. Cases were reviewed by two toxicologists and serotonin toxicity, defined by the Hunter criteria, was diagnosed when appropriate. The literature was then reviewed to evaluate whether chlorphenamine may be a serotonergic agent. One hundred and fifty-five articles of dextromethorphan or chlorphenamine poisoning were identified. There were 23 case reports of dextromethorphan, of which 18 were excluded for lack of serotonin toxicity. No cases were identified in which serotonin toxicity could be solely attributed to chlorphenamine. This left six cases of dextrometorphane and/or chlorphenamine overdose, including our own, in which serotonin toxicity could be diagnosed based on the presented clinical information. In three of the six eligible cases dextromethorphan and chlorphenamine were the only overdosed drugs. There is substantial evidence from the literature that chlorphenamine is a similarly potent serotonin re-uptake inhibitor when compared with dextrometorphan. Chlorphenamine is a serotonergic medication and combinations of chlorphenamine and dextromethorphan may be dangerous in overdose due to an increased risk of serotonin toxicity. PMID:21175434

Toxic element contamination of natural health products and pharmaceutical preparations.

Directory of Open Access Journals (Sweden)

Stephen J Genuis

Full Text Available BACKGROUND: Concern has recently emerged regarding the safety of natural health products (NHPs-therapies that are increasingly recommended by various health providers, including conventional physicians. Recognizing that most individuals in the Western world now consume vitamins and many take herbal agents, this study endeavored to determine levels of toxic element contamination within a range of NHPs. METHODS: Toxic element testing was performed on 121 NHPs (including Ayurvedic, traditional Chinese, and various marine-source products as well as 49 routinely prescribed pharmaceutical preparations. Testing was also performed on several batches of one prenatal supplement, with multiple samples tested within each batch. Results were compared to existing toxicant regulatory limits. RESULTS: Toxic element contamination was found in many supplements and pharmaceuticals; levels exceeding established limits were only found in a small percentage of the NHPs tested and none of the drugs tested. Some NHPs demonstrated contamination levels above preferred daily endpoints for mercury, cadmium, lead, arsenic or aluminum. NHPs manufactured in China generally had higher levels of mercury and aluminum. CONCLUSIONS: Exposure to toxic elements is occurring regularly as a result of some contaminated NHPs. Best practices for quality control-developed and implemented by the NHP industry with government oversight-is recommended to guard the safety of unsuspecting consumers.

Anaerobic toxicity of cationic silver nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Gitipour, Alireza; Thiel, Stephen W. [Biomedical, Chemical, and Environmental Engineering, University of Cincinnati, Cincinnati, OH (United States); Scheckel, Kirk G. [USEPA, Office of Research and Development, Cincinnati, OH (United States); Tolaymat, Thabet, E-mail: tolaymat.thabet@epa.gov [USEPA, Office of Research and Development, Cincinnati, OH (United States)

2016-07-01

The microbial toxicity of silver nanoparticles (AgNPs) stabilized with different capping agents was compared to that of Ag{sup +} under anaerobic conditions. Three AgNPs were investigated: (1) negatively charged citrate-coated AgNPs (citrate-AgNPs), (2) minimally charged polyvinylpyrrolidone coated AgNPs (PVP-AgNPs) and (3) positively charged branched polyethyleneimine coated AgNPs (BPEI-AgNPs). The AgNPs investigated in this experiment were similar in size (10–15 nm), spherical in shape, but varied in surface charge which ranged from highly negative to highly positive. While, at AgNPs concentrations lower than 5 mg L{sup −1}, the anaerobic decomposition process was not influenced by the presence of the nanoparticles, there was an observed impact on the diversity of the microbial community. At elevated concentrations (100 mg L{sup −1} as silver), only the cationic BPEI-AgNPs demonstrated toxicity similar in magnitude to that of Ag{sup +}. Both citrate and PVP-AgNPs did not exhibit toxicity at the 100 mg L{sup −1} as measured by biogas evolution. These findings further indicate the varying modes of action for nanoparticle toxicity and represent one of the few studies that evaluate end-of-life management concerns with regards to the increasing use of nanomaterials in our everyday life. These findings also highlight some of the concerns with a one size fits all approach to the evaluation of environmental health and safety concerns associated with the use of nanoparticles. - Highlights: • At concentrations -1 the anaerobic decomposition process was not impacted. • An impact on the microbial community at concentrations -1 were observed. • At high concentrations (100 mg L{sup −1}), the cationic BPEI-AgNPs demonstrated toxicity. • Toxicity was demonstrated without the presence of oxidative dissolution of silver. • A one size fits all approach for the evaluation of NPs may not be accurate.

Toxicities of diuron and irgarol on the hatchability and early stage development of Artemia salina

OpenAIRE

ALYÜRÜK, Hakan; ÇAVAŞ, Levent

2013-01-01

Booster biocides are widely used in antifouling paints as bioactive agents against fouling organisms. In previously published reports, acute toxicity tests on Artemia salina (Linnaeus, 1758) were only focused on a part of the life cycle of the organism. The aim of this study was to investigate the toxicities of diuron and irgarol on the hatching stage of A. salina. According to the results, diuron significantly decreased the hatching percentage of A. salina cysts and prevented the hatching of...

Application of Ni-63 photo and corona discharge ionization for the analysis of chemical warfare agents and toxic wastes

Science.gov (United States)

Stach, J.; Adler, J.; Brodacki, M.; Doring, H.-R.

1995-01-01

Over the past decade, advances in instrumental design and refinements in the understanding of ion molecule reactions at atmospheric pressure enabled the application of Ion Mobility Spectrometry (IMS) as a simple inexpensive and sensitive analytical method for the detection of organic trace compounds. Positive and negative gas-phase ions for ion mobility spectrometry have been produced by a variety of methods, including photo-ionization, laser multi photon ionization, surface ionization, corona discharge ionization. The most common ion source used in ion mobility spectrometry is a radioactive Ni-63 foil which is favored due to simplicity, stability, convenience, and high selectivity. If reactant ions like (H2O(n)H)(+) or (H2O(n)O2)(-) dominate in the reaction region, nearly all kinds of compounds with a given proton or electron affinity; are ionized. However, the radioactivity of the Ni-63 foil is one disadvantage of this ion source that stimulates the development and application of other ionization techniques. In this paper, we report analyses of old chemical warfare agents and toxic wastes using Bruker RAID ion mobility spectrometers. Due to the modular construction of the measuring cell, the spectrometers can be equipped with different ion sources. The combined use of Ni-63, photo- and corona discharge ionization allows the identification of different classes of chemical compounds and yields in most cases comparable results.

Toxic effects of electrolyte and trace mineral administration in the intensive care unit.

Science.gov (United States)

Besunder, J B; Smith, P G

1991-07-01

Electrolytes and trace minerals are administered routinely to ICU patients to correct deficiencies or as specific therapy for various conditions. Complications are usually related to the rate of infusion, rapidity of correction of a deficiency state, or iatrogenic poisoning with the agent. Adverse effects associated with Na+ administration included volume overload, CPM, and central nervous system bleeds. The toxic effects of K+, Ca2+, and Mg2+ are primarily related to their effects on the myocardium, nervous system, and muscle. Other than precipitating or maintaining a metabolic acidosis, Cl- administration is relatively nontoxic. Its accompanying anion (i.e., ammonium or arginine), however, may contribute significantly to patient morbidity and, possibly, mortality. Side effects observed with phosphate administration include hypocalcemia, metastatic calcification, and hypernatremia or hyperkalemia. Most of these toxicities are avoidable if appropriate precautions are taken and appropriate monitoring implemented. Finally, when administering any of these agents, the intensivist should be familiar with their toxicologic profiles and management of potential complications.

A New Generation of Thermal Desorption Technology Incorporating Multi Mode Sampling (NRT/DAAMS/Liquid Agent) for Both on and off Line Analysis of Trace Level Airbone Chemical Warfare Agents

International Nuclear Information System (INIS)

Roberts, G. M.

2007-01-01

A multi functional, twin-trap, electrically-cooled thermal desorption (TD) system (TT24-7) will be discussed for the analysis of airborne trace level chemical warfare agents. This technology can operate in both military environments (CW stockpile, or destruction facilities) and civilian locations where it is used to monitor for accidental or terrorist release of acutely toxic substances. The TD system interfaces to GC, GCMS or direct MS analytical platforms and provides for on-line continuous air monitoring with no sampling time blind spots and within a near real time (NRT) context. Using this technology enables on-line sub ppt levels of agent detection from a vapour sample. In addition to continuous sampling the system has the capacity for off-line single (DAAMS) tube analysis and the ability to receive an external liquid agent injection. The multi mode sampling functionality provides considerable flexibility to the TD system, allowing continuous monitoring of an environment for toxic substances plus the ability to analyse calibration standards. A calibration solution can be introduced via a conventional sampling tube on to either cold trap or as a direct liquid injection using a conventional capillary split/splitless injection port within a gas chromatograph. Low level (linearity) data will be supplied showing the TT24-7 analyzing a variety of CW compounds including free (underivitised) VX using the three sampling modes described above. Stepwise changes in vapor generated agent concentrations will be shown, and this is cross referenced against direct liquid agent introduction, and the tube sampling modes. This technology is in use today in several geographies around the world in both static and mobile analytical laboratories. (author)

RSDL decontamination of human skin contaminated with the nerve agent VX.

Science.gov (United States)

Thors, L; Lindberg, S; Johansson, S; Koch, B; Koch, M; Hägglund, L; Bucht, A

2017-03-05

Dermal exposure to low volatile organophosphorus compounds (OPC) may lead to penetration through the skin and uptake in the blood circulation. Skin decontamination of toxic OPCs, such as pesticides and chemical warfare nerve agents, might therefore be crucial for mitigating the systemic toxicity following dermal exposure. Reactive skin decontamination lotion (RSDL) has been shown to reduce toxic effects in animals dermally exposed to the nerve agent VX. In the present study, an in vitro flow-through diffusion cell was utilized to evaluate the efficacy of RSDL for decontamination of VX exposed to human epidermis. In particular, the impact of timing in the initiation of decontamination and agent dilution in water was studied. The impact of the lipophilic properties of VX in the RSDL decontamination was additionally addressed by comparing chemical degradation in RSDL and decontamination efficacy between the VX and the hydrophilic OPC triethyl phosphonoacetate (TEPA). The epidermal membrane was exposed to 20, 75 or 90% OPC diluted in deionized water and the decontamination was initiated 5, 10, 30, 60 or 120min post-exposure. Early decontamination of VX with RSDL, initiated 5-10min after skin exposure, was very effective. Delayed decontamination initiated 30-60min post-exposure was less effective but still the amount of penetrated agent was significantly reduced, while further delayed start of decontamination to 120min resulted in very low efficacy. Comparing RSDL decontamination of VX with that of TEPA showed that the decontamination efficacy at high agent concentrations was higher for VX. The degradation mechanism of VX and TEPA during decontamination was dissected by 31 P NMR spectroscopy of the OPCs following reactions with RSDL and its three nucleophile components. The degradation rate was clearly associated with the high pH of the specific solution investigated; i.e. increased pH resulted in a more rapid degradation. In addition, the solubility of the OPC in RSDL

Natural Pathogen Control Chemistry to Replace Toxic Treatment of Microbes and Biofilm in Cooling Towers

Science.gov (United States)

Brouse, Lon; Brouse, Richard; Brouse, Daniel

2017-01-01

Application of toxic antibacterial agents is considered necessary to control prevalent fresh water microorganisms that grow in evaporative cooling water systems, but can adversely affect the environment and human health. However, natural antibacterial water chemistry has been applied in industrial cooling water systems for over 10 years to inhibit microorganisms with excellent results. The water chemistry method concentrates natural minerals in highly-softened water to produce elevated pH and dissolved solids, while maintaining low calcium and magnesium content. The method provides further benefits in water conservation, and generates a small volume of non-toxic natural salt concentrate for cost efficient separation and disposal if required. This report describes the antimicrobial effects of these chemistry modifications in the cooling water environment and the resultant collective inhibition of microbes, biofilm, and pathogen growth. This article also presents a novel perspective of parasitic microbiome functional relationships, including “Trojan Protozoans” and biofilms, and the function of polyvalent metal ions in the formation and inhibition of biofilms. Reducing global dependence on toxic antibacterial agents discharged to the environment is an emerging concern due to their impact on the natural microbiome, plants, animals and humans. Concurrently, scientists have concluded that discharge of antibacterial agents plays a key role in development of pathogen resistance to antimicrobials as well as antibiotics. Use of natural antibacterial chemistry can play a key role in managing the cooling water environment in a more ecologically sustainable manner. PMID:28420074

Toxic polyacetylenes in the genus Bupleurum (Apiaceae) - Distribution, toxicity, molecular mechanism and analysis.

Science.gov (United States)

Lin, Meiyu; Zhang, Weidong; Su, Juan

2016-12-04

The genus Bupleurum includes approximately 200 species that are widely distributed in the Northern Hemisphere, Eurasia and North Africa. Certain species of this genus have long been used as antiphlogistic, antipyretic and analgesic agents in traditional folk medicine. As described in the Chinese Pharmacopoeia, the roots of Bupleurum chinense DC. and B. scorzonerifolium Willd. are the herbal materials that compose Chaihu (Radix Bupleuri), a well-known TCM herb. This review aims to provide up-to-date and comprehensive information regarding the distribution, toxicity, molecular mechanism and relatively new methods for the qualitative and quantitative determination of polyacetylenes in different Bupleurum species. The information needed for this paper were sourced from publishing sites such as Elsevier, science Direct, PubMed; electronic search engines such as Scopus and Web of Science, Google scholar; other scientific database sites for chemicals such as ChemSpider, PubChem, SciFinder, and also from on line books. Polyacetylenes, which are widely distributed in genus Bupleurum of the Apiaceae family, have high toxicity. Among polyacetylenes, bupleurotoxin, acetylbupleurotoxin and oenanthotoxin have strong neurotoxicity. Through previous research, it was found that the toxicity of Bupleurum polyacetylenes manifested as epileptic seizures, with the target of toxicity being the brain. The neurotoxicity of polyacetylenes exhibits a relationship with the γ-aminobutyric acid (GABA) receptor pathway, and polyacetylenes have been shown to inhibit GABA-induced currents (I GABA ) in a competitive manner. The plants of genus Bupleurum have been used in traditional medicine for thousands of years. However, certain species of this genus are poisonous, and it was attributed to the high content of polyacetylenes. The present review indicates that certain polyacetylenes in the genus Bupleurum have highly neurotoxic effects. The major challenge with regard to toxic polyacetylenes is

Use of scanning electron microscopy to monitor nanofibre/cell interaction in digestive epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Millaku, Agron, E-mail: agron.mi@hotmail.com [Limnos-Company for Applied Ecology Ltd, Podlimbarskega 31, 1000 Ljubljana (Slovenia); Drobne, Damjana [University of Ljubljana, Biotechnical Faculty, Department of Biology, Večna pot 111, 1000 Ljubljana (Slovenia); Centre of Excellence, Advanced Materials and Technologies for the Future (CO NAMASTE), Jamova cesta 39, 1000 Ljubljana (Slovenia); Centre of Excellence, Nanoscience and Nanotechnology (Nanocentre), Jamova cesta 39, 1000 Ljubljana (Slovenia); Torkar, Matjaz [Institute of Metals and Technology IMT, Lepi pot 11, 1000 Ljubljana (Slovenia); Jožef Stefan Institute, Condensed Matter Physics Department, Jamova cesta 39, 1000 Ljubljana (Slovenia); Novak, Sara [University of Ljubljana, Biotechnical Faculty, Department of Biology, Večna pot 111, 1000 Ljubljana (Slovenia); Remškar, Maja [Jožef Stefan Institute, Condensed Matter Physics Department, Jamova cesta 39, 1000 Ljubljana (Slovenia); Pipan-Tkalec, Živa [University of Ljubljana, Biotechnical Faculty, Department of Biology, Večna pot 111, 1000 Ljubljana (Slovenia)

2013-09-15

Graphical abstract: Scanning electron microscopy is particularly well suited to the observation of nanofibre/cell interaction in the endothelial cells lining the hepatopancreas. (a) Tungsten oxide nanofibres, (b) test organism Porcellio scaber and schematic appearance of digestive tubes, (c) digestive tube (hepatopancreas) prepared for SEM investigation, (d) digestive gland cells (C) with nanofibres (NF) embedded in the cell membrane and (e) nanofibres inserted deeply in the cells and damaged nanofibres due to peristalsis. -- Highlights: • Tungsten oxide nanofibres react physically with digestive gland epithelial cells in Porcellio scaber. • Physical peristaltic forces of lead to insertion of nanofibres into the cells. • No toxic responses as measured by conventional toxicity biomarkers were detected. • Physical interactions were observed in a majority of the investigated animals. -- Abstract: We provide data obtained by scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) on the interaction of ingested tungsten nanofibers with epithelial cells of the digestive tubes of a test organism Porcellio scaber. Conventional toxicity endpoints including feeding behaviour, weight loss and mortality were also measured in each investigated animal. No toxicity was detected in any of exposed animals after 14 days of feeding on tungsten nanofiber dosed food, but when nanofibers enter the digestive system they can react with epithelial cells of the digestive tubes, becoming physically inserted into the cells. In this way, nanofibers can injure the epithelial cells of digestive gland tubes when they are ingested with food. Our SEM data suggest that peristaltic forces may have an important role, not predicted by in vitro experiments, in the interactions of nanomaterials with digestive intestinal cells.

Use of scanning electron microscopy to monitor nanofibre/cell interaction in digestive epithelial cells

International Nuclear Information System (INIS)

Millaku, Agron; Drobne, Damjana; Torkar, Matjaz; Novak, Sara; Remškar, Maja; Pipan-Tkalec, Živa

2013-01-01

Graphical abstract: Scanning electron microscopy is particularly well suited to the observation of nanofibre/cell interaction in the endothelial cells lining the hepatopancreas. (a) Tungsten oxide nanofibres, (b) test organism Porcellio scaber and schematic appearance of digestive tubes, (c) digestive tube (hepatopancreas) prepared for SEM investigation, (d) digestive gland cells (C) with nanofibres (NF) embedded in the cell membrane and (e) nanofibres inserted deeply in the cells and damaged nanofibres due to peristalsis. -- Highlights: • Tungsten oxide nanofibres react physically with digestive gland epithelial cells in Porcellio scaber. • Physical peristaltic forces of lead to insertion of nanofibres into the cells. • No toxic responses as measured by conventional toxicity biomarkers were detected. • Physical interactions were observed in a majority of the investigated animals. -- Abstract: We provide data obtained by scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) on the interaction of ingested tungsten nanofibers with epithelial cells of the digestive tubes of a test organism Porcellio scaber. Conventional toxicity endpoints including feeding behaviour, weight loss and mortality were also measured in each investigated animal. No toxicity was detected in any of exposed animals after 14 days of feeding on tungsten nanofiber dosed food, but when nanofibers enter the digestive system they can react with epithelial cells of the digestive tubes, becoming physically inserted into the cells. In this way, nanofibers can injure the epithelial cells of digestive gland tubes when they are ingested with food. Our SEM data suggest that peristaltic forces may have an important role, not predicted by in vitro experiments, in the interactions of nanomaterials with digestive intestinal cells

Comparison of 6-thioguanine-resistant mutation and sister chromatid exchanges in Chinese hamster V79 cells with forty chemical and physical agents

International Nuclear Information System (INIS)

Nishi, Y.; Hasegawa, M.M.; Taketomi, M.; Ohkawa, Y.; Inui, N.

1984-01-01

The induction of sister chromatid exchanges (SCE) and mutation at the hypoxanthine-guanine phosphoribosyl transferase locus and toxicities of 40 different chemical and physical agents were examined on Chinese hamster V79 cells. These agents included mono-, di-, tri-, and polyfunctional alkylating agents, intercalators, gamma-rays, and UV light irradiation. Mutation was measured as resistance to 6-thioguanine and toxicity as loss of cell-plating efficiency. SCE were examined 29 hr after treatment. With the agents examined, a highly positive correlation existed between SCE-inducing and mutagenic potencies, when expressed as increase in the number per a unit dose over the control values. But the great difference of the ratios of mutagenic potencies versus SCE-inducing potencies among agents was observed, the maximal difference in the ratios being about 200-fold. The agents that showed the higher values of the ratio (agents producing more mutations than SCE) were bleomycin, cobalt-60 gamma-rays, all ethylating agents (N-ethyl-N-nitrosourea, N-ethyl-N'-nitro-N-nitrosoguanidine, ethyl methanesulfonate, and diethylsulfate), N-propyl-N-nitrosourea, N-butyl-N-nitrosourea, isopropyl methanesulfonate, intercalating acridine compounds (2-methoxy-6-chloro-9-[3-(ethyl-2-chloroethyl)aminopropylamino]-acridine X 2HCl and 2-methoxy-6-chloro-9-[3-(chloroethyl)-aminopropylamino]acridine 2HCl) and UV light at 254 nm

SERIES: Genomic instability in cancer Balancing repair and tolerance of DNA damage caused by alkylating agents

Science.gov (United States)

Fu, Dragony; Calvo, Jennifer A.; Samson, Leona D

2013-01-01

Alkylating agents comprise a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER), and mismatch repair (MMR) respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for an organism's favorable response to alkylating agents. Furthermore, an individual's response to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity. PMID:22237395

Digoxin Toxicity in a 14 Days Old Newborn: A Case Report

Directory of Open Access Journals (Sweden)

İclal Sucaklı

2006-01-01

Full Text Available Digoxin is one of the most commonly used positive inotropic agent. Digitalis toxicity may occur easily because of digoxin has a narrow therapeutic window. Digitalis toxicity may result during treatment with digoxin or from accidental overdose of digoxin. An elevated serum level of digoxin (>2ng/ml is likely to be associated with toxicity, overdose of digoxin (>5ng/ml may lead to life-threatening arrhythmias. A 14-days old newborn with VSD, which had been prescribed the droplet form of digoxin but given the tablet form by the drugstore, was diagnosed as digitalis toxicity and hospitalized to our clinic. His mother expressed that she had given two tablets mashed with spoon and diluted. Bradycardia and grade 3/6 pansystolic murmur was determined in physical examination. Digoxin level in serum was >5 ng/ml and there was third degree atrioventricular block in ECG findings. The case has been presented to emphasize the importance of better evaluation of digoxin indications and making families of the patients conscious of the usage of digoxin.

Technical considerations on scanning and image analysis for amyloid PET in dementia

International Nuclear Information System (INIS)

Akamatsu, Go; Ohnishi, Akihito; Aita, Kazuki; Ikari, Yasuhiko; Senda, Michio; Yamamoto, Yasuji

2017-01-01

Brain imaging techniques, such as computed tomography (CT), magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET), can provide essential and objective information for the early and differential diagnosis of dementia. Amyloid PET is especially useful to evaluate the amyloid-β pathological process as a biomarker of Alzheimer's disease. This article reviews critical points about technical considerations on the scanning and image analysis methods for amyloid PET. Each amyloid PET agent has its own proper administration instructions and recommended uptake time, scan duration, and the method of image display and interpretation. In addition, we have introduced general scanning information, including subject positioning, reconstruction parameters, and quantitative and statistical image analysis. We believe that this article could make amyloid PET a more reliable tool in clinical study and practice. (author)

Technical Considerations on Scanning and Image Analysis for Amyloid PET in Dementia.

Science.gov (United States)

Akamatsu, Go; Ohnishi, Akihito; Aita, Kazuki; Ikari, Yasuhiko; Yamamoto, Yasuji; Senda, Michio

2017-01-01

Brain imaging techniques, such as computed tomography (CT), magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET), can provide essential and objective information for the early and differential diagnosis of dementia. Amyloid PET is especially useful to evaluate the amyloid-β pathological process as a biomarker of Alzheimer's disease. This article reviews critical points about technical considerations on the scanning and image analysis methods for amyloid PET. Each amyloid PET agent has its own proper administration instructions and recommended uptake time, scan duration, and the method of image display and interpretation. In addition, we have introduced general scanning information, including subject positioning, reconstruction parameters, and quantitative and statistical image analysis. We believe that this article could make amyloid PET a more reliable tool in clinical study and practice.

Halide test agent replacement study

Energy Technology Data Exchange (ETDEWEB)

Banks, E.M.; Freeman, W.P.; Kovach, B.J. [and others

1995-02-01

The intended phaseout of the chlorofluorocarbons (CFCs) from commercial use required the evaluation of substitute materials for the testing for leak paths through both individual adsorbers and installed adsorbent banks. The American Society of Mechanical Engineers (ASME) Committee on Nuclear Air and Gas Treatment (CONAGT) is in charge of maintaining the standards and codes specifying adsorbent leak test methods for the nuclear safety related air cleaning systems. The currently published standards and codes cite the use of R-11, R-12 and R-112 for leak path test agents. All of these compounds are CFCs. There are other agencies and organizations (USDOE, USDOD and USNRC) also specifying testing for leak paths or in some cases for special life tests using the above compounds. The CONAGT has recently developed criteria for the suitability evaluation of substitute test agents. On the basis of these criteria, several compounds were evaluated for their acceptability as adsorbent bed leak and life test agents. The ASME CONAGT Test Agent Qualification Criteria. The test agent qualification is based on the following parameters: (1) Similar retention times on activated carbons at the same concentration levels as one of the following: R-11, R-12, R-112 or R-112a. (2) Similar lower detection limit sensitivity and precision in the concentration range of use as R-11, R-12, R-112 and R-112a. (3) Gives the same in-place leak test results as R-11, R-12, R-112, or R-112a. (4) Chemical and radiological stability under the use conditions. (5) Causes no degradation of the carbon and its impregnant or of the other NATS components under the use conditions. (6) Is listed in the USEPA Toxic Substances Control Act (TSCA) inventory for commercial use.

Comparison and avoidance of toxicity of penetrating cryoprotectants.

Directory of Open Access Journals (Sweden)

Edyta A Szurek

Full Text Available The objective of this study was to elucidate the toxicity of widely used penetrating cryoprotective agents (CPAs to mammalian oocytes. To this end, mouse metaphase II (M II oocytes were exposed to 1.5 M solutions of dimethylsulfoxide (DMSO, ethylene glycol (EG, or propanediol (PROH prepared in phosphate buffered saline (PBS containing 10% fetal bovine serum. To address the time- and temperature-dependence of the CPA toxicity, M II oocytes were exposed to the aforementioned CPAs at room temperature (RT, ∼23°C and 37°C for 15 or 30 minutes. Subsequently, the toxicity of each CPA was evaluated by examining post-exposure survival, fertilization, embryonic development, chromosomal abnormalities, and parthenogenetic activation of treated oocytes. Untreated oocytes served as controls. Exposure of MII oocytes to 1.5 M DMSO or 1.5 M EG at RT for 15 min did not adversely affect any of the evaluated criteria. In contrast, 1.5 M PROH induced a significant increase in oocyte degeneration (54.2% and parthenogenetic activation (16% under same conditions. When the CPA exposure was performed at 37°C, the toxic effect of PROH further increased, resulting in lower survival (15% and no fertilization while the toxicity of DMSO and EG was still insignificant. Nevertheless, it was possible to completely avoid the toxicity of PROH by decreasing its concentration to 0.75 M and combining it with 0.75 M DMSO to bring the total CPA concentration to a cryoprotective level. Moreover, combining lower concentrations (i.e., 0.75 M of PROH and DMSO significantly improved the cryosurvival of MII oocytes compared to the equivalent concentration of DMSO alone. Taken together, our results suggest that from the perspective of CPA toxicity, DMSO and EG are safer to use in slow cooling protocols while a lower concentration of PROH can be combined with another CPA to avoid its toxicity and to improve the cryosurvival as well.

N-cinnamoylated aminoquinolines as promising antileishmanial agents.

Science.gov (United States)

Vale-Costa, S; Costa-Gouveia, J; Pérez, B; Silva, T; Teixeira, C; Gomes, P; Gomes, M S

2013-10-01

A series of cinnamic acid conjugates of primaquine and chloroquine were evaluated for their in vitro antileishmanial activities. Although primaquine derivatives had modest activity, chloroquine conjugates exhibited potent activity against both promastigotes (50% inhibitory concentration [IC50] = 2.6 to 21.8 μM) and intramacrophagic amastigotes (IC50 = 1.2 to 9.3 μM) of Leishmania infantum. Both the high activity of these chloroquine analogues and their mild-to-low toxicity toward host cells make them promising leads for the discovery of new antileishmanial agents.

Comparison of simultaneous 99mTc-HMPAO and 111In oxine labelled white cell scans in the assessment of inflammatory bowel disease

International Nuclear Information System (INIS)

Allan, R.A.; Bassingham, S.; Lazarus, C.; Clarke, S.E.M.; Fogelman, I.; Sladen, G.E.

1993-01-01

Forty-seven patients, 29 with chronic inflammatory bowel disease (IBD) and 18 with presumed irritable bowel syndrome, including one with uncomplicated diverticular disease, were studied with simultaneous technetium-99m hexamethylpropylene amine oxime and indium-III oxine labelled leucocyte scans performed at 1, 3 and 24 h. Twenty-seven patients with IBD had active disease as judged by clinical and laboratory criteria and all of these had positive scans with both agents. No false positive studies were obtained. The 1-h 99m Tc-HMPAO WBC scans showed the same distribution to disease as the 3-h 111 -In WBC scans, with no difference in intensity (P 111 -In scans. The 3-h 99m Tc-HMPAO WBC scans showed more extensive disease (P 111 In WBC scans. Physiological bowel activity on 3-h 99m Tc-HMPAO WBC scans was present in 12 patients but was faint and did not interfere with assessment of disease extent and activity. It is concluded that in terms of isotope availability, radiation dosimetry and image quality, 99m Tc-HMPAO is the agent of choice in detecting active IBD, with localization of disease possible at 1-h after re-injection and optimal resolution and definition of disease extent at 3 h. A negative scan reliably excludes active disease. (orig.)

Pharmacologic treatment of acute pediatric methamphetamine toxicity.

Science.gov (United States)

Ruha, Anne-Michelle; Yarema, Mark C

2006-12-01

To report our experience with the use of benzodiazepines and haloperidol for sedation of pediatric patients with acute methamphetamine poisoning. We performed a retrospective chart review of 18 pediatric patients who were admitted to an intensive care unit for methamphetamine toxicity from January 1997 to October 2004 and treated with benzodiazepines or haloperidol. Clinical features, dose of drug received, and laboratory test results were noted. Adverse effects from the use of haloperidol such as prolonged QTc, dystonic reactions, and torsades de pointes were recorded. Eighteen patients received a benzodiazepine, the dose of which varied depending on the agent used. Twelve patients also received parenteral haloperidol. No complications developed from the use of either haloperidol or benzodiazepines. In this case series of pediatric patients poisoned with methamphetamine, parenteral benzodiazepines and haloperidol were used to control agitation. No serious adverse effects were observed from the use of these agents.

Oxidative decontamination of chemical and biological warfare agents using L-Gel.

Science.gov (United States)

Raber, Ellen; McGuire, Raymond

2002-08-05

A decontamination method has been developed using a single reagent that is effective both against chemical warfare (CW) and biological warfare (BW) agents. The new reagent, "L-Gel", consists of an aqueous solution of a mild commercial oxidizer, Oxone, together with a commercial fumed silica gelling agent, Cab-O-Sil EH-5. L-Gel is non-toxic, environmentally friendly, relatively non-corrosive, maximizes contact time because of its thixotropic nature, clings to walls and ceilings, and does not harm carpets or painted surfaces. The new reagent also addresses the most demanding requirements for decontamination in the civilian sector, including availability, low maintenance, ease of application and deployment by a variety of dispersal mechanisms, minimal training and acceptable expense. Experiments to test the effectiveness of L-Gel were conducted at Lawrence Livermore National Laboratory and independently at four other locations. L-Gel was tested against all classes of chemical warfare agents and against various biological warfare agent surrogates, including spore-forming bacteria and non-virulent strains of real biological agents. Testing showed that L-Gel is as effective against chemical agents and biological materials, including spores, as the best military decontaminants.

Pemphigus Vulgaris with Solitary Toxic Thyroid Nodule

Directory of Open Access Journals (Sweden)

Mostafa Alfishawy

2014-01-01

Full Text Available Background. Pemphigus vulgaris is an autoimmune vesiculobullous disease, affecting the skin and mucous membranes. It is reported to be associated with other autoimmune diseases including autoimmune thyroid diseases. However we report herein a case of pemphigus vulgaris associated with autonomous toxic nodule. Case Presentation. A 51-year-old woman was evaluated for blisters and erosions that develop on her trunk, face, and extremities, with a five-year history of progressively enlarging neck mass, and a past medical history of pemphigus vulgaris seven years ago. The condition was associated with palpitation, dyspnea, and heat intolerance. Thyroid function tests and thyroid scan were compatible with the diagnosis of thyrotoxicosis due to autonomous toxic nodule. Exacerbation of pemphigus vulgaris was proved by skin biopsy from the patient which revealed histologic picture of pemphigus vulgaris. Conclusion. Autoimmune thyroid diseases are reported to associate pemphigus vulgaris. To our knowledge, this case is the first in the English literature to report association between pemphigus vulgaris and autonomous toxic nodule and highlights the possibility of occurrence of pemphigus vulgaris with a nonautoimmune thyroid disease raising the question: is it just a coincidence or is there an explanation for the occurrence of both conditions together?

Genomic phenotyping by barcode sequencing broadly distinguishes between alkylating agents, oxidizing agents, and non-genotoxic agents, and reveals a role for aromatic amino acids in cellular recovery after quinone exposure.

Directory of Open Access Journals (Sweden)

J Peter Svensson

Full Text Available Toxicity screening of compounds provides a means to identify compounds harmful for human health and the environment. Here, we further develop the technique of genomic phenotyping to improve throughput while maintaining specificity. We exposed cells to eight different compounds that rely on different modes of action: four genotoxic alkylating (methyl methanesulfonate (MMS, N-Methyl-N-nitrosourea (MNU, N,N'-bis(2-chloroethyl-N-nitroso-urea (BCNU, N-ethylnitrosourea (ENU, two oxidizing (2-methylnaphthalene-1,4-dione (menadione, MEN, benzene-1,4-diol (hydroquinone, HYQ, and two non-genotoxic (methyl carbamate (MC and dimethyl sulfoxide (DMSO compounds. A library of S. cerevisiae 4,852 deletion strains, each identifiable by a unique genetic 'barcode', were grown in competition; at different time points the ratio between the strains was assessed by quantitative high throughput 'barcode' sequencing. The method was validated by comparison to previous genomic phenotyping studies and 90% of the strains identified as MMS-sensitive here were also identified as MMS-sensitive in a much lower throughput solid agar screen. The data provide profiles of proteins and pathways needed for recovery after both genotoxic and non-genotoxic compounds. In addition, a novel role for aromatic amino acids in the recovery after treatment with oxidizing agents was suggested. The role of aromatic acids was further validated; the quinone subgroup of oxidizing agents were extremely toxic in cells where tryptophan biosynthesis was compromised.

Treating exposure to chemical warfare agents: implications for health care providers and community emergency planning.

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Munro, N B; Watson, A P; Ambrose, K R; Griffin, G D

1990-01-01

Current treatment protocols for exposure to nerve and vesicant agents found in the U.S. stockpile of unitary chemical weapons are summarized, and the toxicities of available antidotes are evaluated. The status of the most promising of the new nerve agent antidotes is reviewed. In the U.S. atropine and pralidoxime compose the only approved antidote regimen for organophosphate nerve agent poisoning. Diazepam may also be used if necessary to control convulsions. To avoid death, administration must occur within minutes of substantial exposure together with immediate decontamination. Continuous observation and repeated administration of antidotes are necessary as symptoms warrant. Available antidotes do not necessarily prevent respiratory failure or incapacitation. The toxicity of the antidotes themselves and the individualized nature of medical care preclude recommending that autoinjectors be distributed to the general public. In addition, precautionary administration of protective drugs to the general population would not be feasible or desirable. No antidote exists for poisoning by the vesicant sulfur mustard (H, HD, HT); effective intervention can only be accomplished by rapid decontamination followed by palliative treatment of symptoms. British anti-Lewisite (BAL) (2,3-dimercapto-1-propanolol) is the antidote of choice for treatment of exposure to Lewisite, another potent vesicant. Experimental water-soluble BAL analogues have been developed that are less toxic than BAL. Treatment protocols for each antidote are summarized in tabular form for use by health care providers. PMID:2088748

Development and applications of radiotracers technologies and gamma scanning

International Nuclear Information System (INIS)

Conejo, Mario; Chaverri, Oscar; Chine, Bruno; Vargas, Celso

2008-01-01

The radiotracers and gamma scanning technologies are very consolidated tools for studying, analyzing and evaluating of industrial processes. The development and the results of radiotracers and gamma scanning technologies applied in laboratory and more complex systems, are reported. The radiotracers technology was used to study boron diffusion during the curing process of the wood, to evaluate a lagoon of sewage treatment with aquatic iris plants and to carry out experimental work with controlled variables in a laboratory hydraulic circuit (flow rig). The gamma scanning technique was used to analyze a pilot tower in the laboratories. The main results achieved with the experiments were the following: 1) the boron absorption as a wood curing agent depends on the section of wood exposed to the curing solution; 2) during the tests effectuated with Iodine 131, the aquatic iris plants situated in the water treatment lagoon absorb part of the radiotracer, making difficult the residence time determination; 3) the sensibility of the system Cesium 137 source and detector is sufficiently high and can detect low radioactive absorption materials, situated inside columns with steel walls. (author) [es

Hydroquinone: Environmental Pollution, Toxicity, and Microbial Answers

Directory of Open Access Journals (Sweden)

Francisco J. Enguita

2013-01-01

Full Text Available Hydroquinone is a major benzene metabolite, which is a well-known haematotoxic and carcinogenic agent associated with malignancy in occupational environments. Human exposure to hydroquinone can occur by dietary, occupational, and environmental sources. In the environment, hydroquinone showed increased toxicity for aquatic organisms, being less harmful for bacteria and fungi. Recent pieces of evidence showed that hydroquinone is able to enhance carcinogenic risk by generating DNA damage and also to compromise the general immune responses which may contribute to the impaired triggering of the host immune reaction. Hydroquinone bioremediation from natural and contaminated sources can be achieved by the use of a diverse group of microorganisms, ranging from bacteria to fungi, which harbor very complex enzymatic systems able to metabolize hydroquinone either under aerobic or anaerobic conditions. Due to the recent research development on hydroquinone, this review underscores not only the mechanisms of hydroquinone biotransformation and the role of microorganisms and their enzymes in this process, but also its toxicity.

Zirconium Hydroxide-coated Nanofiber Mats for Nerve Agent Decontamination.

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Kim, Sohee; Ying, Wu Bin; Jung, Hyunsook; Ryu, Sam Gon; Lee, Bumjae; Lee, Kyung Jin

2017-03-16

Diverse innovative fabrics with specific functionalities have been developed for requirements such as self-decontamination of chemical/biological pollutants and toxic nerve agents. In this work, Zr(OH) 4 -coated nylon-6,6 nanofiber mats were fabricated for the decontamination of nerve agents. Nylon-6,6 fabric was prepared via the electrospinning process, followed by coating with Zr(OH) 4 , which was obtained by the hydrolysis of Zr(OBu) 4 by a sol-gel reaction on nanofiber surfaces. The reaction conditions were optimized by varying the amounts of Zr(OBu) 4 ,the reaction time, and the temperature of the sol-gel reaction. The composite nanofibers show high decontamination efficiency against diisopropylfluorophosphate, which is a nerve agent analogue, due to its high nucleophilicity that aids in the catalysis of the hydrolysis of the phosphonate ester bonds. Composite nanofiber mats have a large potential and can be applied in specific fields such as military and medical markets. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Marine toxicity and persistence of surfactants used in the petroleum producing industry

International Nuclear Information System (INIS)

Maddin, C.M.

1991-01-01

This paper presents a survey of marine toxicity and biodegradability data for surfactants used in the petroleum industry. Surfactants are key chemicals in the formulation of products such as emulsifiers, demulsifiers, dispersants and inhibitors. They are also used directly as foaming and defoaming agents. Because they function at low concentrations, below 1%, and have a tendency to adsorb on solid surfaces, their long-term environmental effects are minimal. In applications such as cementing, surfactants cannot migrate into the environment and, thus, have no bioavailability. The possibility of environmental contamination has caused well operators and regulatory agencies to require fish toxicity and persistence data for products used in servicing wells. This data has been organized for nonionic, anionic, cationic and amphoteric surfactants. Nonionic surfactants are toxic to fish at concentrations below 10 mg/L to over 2500 mg/L depending on their chemical compositions. Anionic surfactants are toxic to fish at concentrations under 1 mg/L to several hundred mg/L depending on their chemical compositions. cationic and amphoteric surfactants are generally toxic to fish at concentrations below 50 mg/L. Overall efforts are aimed at low toxicity and high biodegradability with the least compromise in product efficiency. This requires the continual testing and environmental evaluation of surfactants summarized herein

Triclosan: environmental exposure, toxicity and mechanisms of action.

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Dann, Andrea B; Hontela, Alice

2011-05-01

Triclosan [5-chloro-2-(2,4-dichlorophenoxy)phenol; TCS] is a broad spectrum antibacterial agent used in personal care, veterinary, industrial and household products. TCS is commonly detected in aquatic ecosystems, as it is only partially removed during the wastewater treatment process. Sorption, biodegradation and photolytic degradation mitigate the availability of TCS to aquatic biota; however the by-products such as methyltriclosan and other chlorinated phenols may be more resistant to degradation and have higher toxicity than the parent compound. The continuous exposure of aquatic organisms to TCS, coupled with its bioaccumulation potential, have led to detectable levels of the antimicrobial in a number of aquatic species. TCS has been also detected in breast milk, urine and plasma, with levels of TCS in the blood correlating with consumer use patterns of the antimicrobial. Mammalian systemic toxicity studies indicate that TCS is neither acutely toxic, mutagenic, carcinogenic, nor a developmental toxicant. Recently, however, concern has been raised over TCS's potential for endocrine disruption, as the antimicrobial has been shown to disrupt thyroid hormone homeostasis and possibly the reproductive axis. Moreover, there is strong evidence that aquatic species such as algae, invertebrates and certain types of fish are much more sensitive to TCS than mammals. TCS is highly toxic to algae and exerts reproductive and developmental effects in some fish. The potential for endocrine disruption and antibiotic cross-resistance highlights the importance of the judicious use of TCS, whereby the use of TCS should be limited to applications where it has been shown to be effective. Copyright © 2011 John Wiley & Sons, Ltd.

Oxaliplatin-induced Oxidative Stress Provokes Toxicity in Isolated Rat Liver Mitochondria.

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Tabassum, Heena; Waseem, Mohammad; Parvez, Suhel; Qureshi, M Irfan

2015-11-01

Oxaliplatin is a widely employed platinum-derived chemotherapeutic agent commonly used for the treatment of colorectal cancer. Unfortunately, the benefit of this important drug is compromised by severe side effects such as neuropathy, ototoxicity, gastrointestinal toxicity, and hematological toxicity. Recently, few studies have also suggested the occurrence of hepatotoxicity in oxaliplatin-treated patients. Mitochondria have emerged as targets for anticancer drugs in various kinds of toxicity including hepatotoxicity that can lead to neoplastic disease. Oxidative stress is a well-established biomarker of mitochondrial toxicity. The purpose of this study was to investigate the dose-dependent damage caused by oxaliplatin on isolated liver mitochondria under in vitro conditions. The study was conducted in mitochondria isolated from liver of Wistar rats. Oxaliplatin was incubated with mitochondria in a dose-dependent manner under in vitro conditions. Oxidative stress indexes, non-enzymatic and enzymatic antioxidants were evaluated, looking at the overall armamentarium against the toxicity induced by oxaliplatin. Oxaliplatin caused a significant rise in the mitochondrial oxidative stress indexes lipid peroxidation and protein carbonyl. Alterations in the levels of non-enzymatic antioxidants and activities of enzymatic antioxidants were also observed. Oxidative stress plays an important role in the mitochondrial toxicity of oxaliplatin. The integrity of the hepatic tissue is compromised by the reactive oxygen species-mediated lipid peroxidation and protein carbonyl formation. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

Toxicity of noradrenaline, a novel anti-biofouling component, to two non-target zooplankton species, Daphnia magna and Ceriodaphnia dubia.

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Overturf, C L; Wormington, A M; Blythe, K N; Gohad, N V; Mount, A S; Roberts, A P

2015-05-01

Noradrenaline (NA) is the active component of novel antifouling agents and acts by preventing attachment of fouling organisms. The goal of this study was to examine the toxicity of NA to the non-target zooplankton D. magna and C. dubia. Neonates were exposed to one of five concentrations of NA and effects on survival, reproduction and molting were determined. Calculated LC50 values were determined to be 46 and 38 μM in C. dubia and D. magna, respectively. A 10-day C. dubia study found that reproduction metrics were significantly impacted at non-lethal concentrations. In D. magna, concentrations greater than 40 μM significantly impacted molting. A toxicity test was conducted with D. magna using oxidized NA, which yielded similar results. These data indicate that both NA and oxidized NA are toxic to non-target zooplankton. Results obtained from this study can be used to guide future ecological risk assessments of catecholamine-based antifouling agents. Copyright © 2015. Published by Elsevier Inc.

A categorical structure-activity relationship analysis of the developmental toxicity of antithyroid drugs.

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Cunningham, Albert R; Carrasquer, C Alex; Mattison, Donald R

2009-01-01

The choice of therapeutic strategies for hyperthyroidism during pregnancy is limited. Surgery and radioiodine are typically avoided, leaving propylthiouracil and methimazole in the US. Carbimazole, a metabolic precursor of methimazole, is available in some countries outside of the US. In the US propylthiouracil is recommended because of concern about developmental toxicity from methimazole and carbimazole. Despite this recommendation, the data on developmental toxicity of all three agents are extremely limited and insufficient to support a policy given the broad use of methimazole and carbimazole around the world. In the absence of new human or animal data we describe the development of a new structure-activity relationship (SAR) model for developmental toxicity using the cat-SAR expert system. The SAR model was developed from data for 323 compounds evaluated for human developmental toxicity with 130 categorized as developmental toxicants and 193 as nontoxicants. Model cross-validation yielded a concordance between observed and predicted results between 79% to 81%. Based on this model, propylthiouracil, methimazole, and carbimazole were observed to share some structural features relating to human developmental toxicity. Thus given the need to treat women with Graves's disease during pregnancy, new molecules with minimized risk for developmental toxicity are needed. To help meet this challenge, the cat-SAR method would be a useful in screening new drug candidates for developmental toxicity as well as for investigating their mechanism of action.

Scanning Electron Microscopy and Energy-Dispersive X-Ray Microanalysis of Set CEM Cement after Application of Different Bleaching Agents.

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Samiei, Mohammad; Janani, Maryam; Vahdati, Amin; Alemzadeh, Yalda; Bahari, Mahmoud

2017-01-01

The present study evaluated the element distribution in completely set calcium-enriched mixture (CEM) cement after application of 35% carbamide peroxide, 40% hydrogen peroxide and sodium perborate as commercial bleaching agents using an energy-dispersive x-ray microanalysis (EDX) system. The surface structure was also observed using the scanning electron microscope (SEM). Twenty completely set CEM cement samples, measuring 4×4 mm 2 , were prepared in the present in vitro study and randomly divided into 4 groups based on the preparation technique as follows: the control group; 35% carbamide peroxide group in contact for 30-60 min for 4 times; 40% hydrogen peroxide group with contact time of 15-20 min for 3 times; and sodium perborate group, where the powder and liquid were mixed and placed on CEM cement surface 4 times. Data were analyzed at a significance level of 0.05 through the one Way ANOVA and Tukey's post hoc tests. EDX showed similar element distribution of oxygen, sodium, calcium and carbon in CEM cement with the use of carbamide peroxide and hydroxide peroxide; however, the distribution of silicon was different ( P structure. Sodium perborate was similar to control group due to its weak oxidizing properties. Globular structures and numerous woodpecker holes were observed on the even surface on the carbamide peroxide group. The mean elemental distribution of completely set CEM cement was different when exposed to sodium perborate, carbamide peroxide and hydrogen peroxide.

The experimental studies of Chinese herbs as a vascular embolization agent for the hepatic arteries

International Nuclear Information System (INIS)

Chen Ziqian; Yang Xizhang; Shen Junjie; Wang Shudong; Zheng Xiaogang; Cao Jianmin

2006-01-01

Objective: To study the efficacy, safety and correlative characteristics of Chinese herb as a vascular embolization agent. Methods: Vascular embolization agent combined from several kinds of Chinese herb was manufactured and served as anticarcinogen and coagulant according to the chinese Pharmacopoeia. The characteristics of the combination embolization agent through embolizing the hepatic arteries in eight pigs were studied. Results: The combination agent was a non-homogenous suspension, easily to be injected through 5-F catheter with hyper attenuation under fluoroscopy; simultaneously with good histocompatibility and hemo-compatibility and without feverish response and toxicity. The combination agent mainly embolized the peripheral arteries with maintaining occlusion for 5 weeks and without formation of collateral circulation. Slight injuries of normal hepatic tissues with hepatic cytonecrosis and endochyloma focal necrosis were found through optical and electronic microscopy. Conclusions: The Chinese herb combination agent is safe and effective in experimental application with good angioembolic function and a potential peripheral embolization agent. (authors)

X-ray fluorescent scanning of the thyroid

International Nuclear Information System (INIS)

Jonckheer, M.H.; Deconinck, F.

1983-01-01

The main emphasis of the technical chapters of this monograph lies on the aspects which are of direct importance to thyroid scanning: the general principles of X-ray fluorescence, the choice and characteristics of appropriate sources and detectors, a stationary system, quantification problems, and the pitfalls in the interpretation of the intrathyroidal iodine imaging and quantification. The clinical part of the monograph consists of chapters on the role of stable iodine and the thyroid function, on endemic non-toxic goiter, on hyperthyroidism as a result of iodine overload, on feasibility of dynamic studies, on stable iodine stores in thyroiditis, and on a general review of the clinical usefulness of XRF in thyroid disease. (Auth.)

Cardiotonic agent milrinone stimulates resorption in rodent bone organ culture.

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Krieger, N S; Stappenbeck, T S; Stern, P H

1987-01-01

The cardiotonic agent amrinone inhibits bone resorption in vitro. Milrinone, an amrinone analog, is a more potent cardiotonic agent with lower toxicity. In contrast to amrinone, milrinone stimulated resorption in cultures of neonatal mouse calvaria and fetal rat limb bones. Threshold doses were 0.1 microM in calvaria and 0.1 mM in limb bones; maximal stimulation occurred in calvaria at 0.1 mM. Maximal responses to milrinone and parathyroid hormone were comparable. Milrinone concentrations below 0.1 mM did not affect calvarial cyclic AMP. 0.5 microM indomethacin inhibited milrinone effects in calvaria but usually not in limb bones. 3 nM calcitonin inhibited milrinone-stimulated resorption and there was no escape from this inhibition. Structural homology between milrinone and thyroxine has been reported. We find similarities between milrinone and thyroxine actions on bone, because prostaglandin production was crucial for the effects of both agents in calvaria but not in limb bones, and neither agent exhibited escape from calcitonin inhibition. PMID:3027124

Medicinal plants and natural products in amelioration of arsenic toxicity: a short review.

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Bhattacharya, Sanjib

2017-12-01

Chronic arsenic toxicity (arsenicosis) is considered a serious public health menace worldwide, as there is no specific, safe, and efficacious therapeutic management of arsenicosis. To collate the studies on medicinal plants and natural products with arsenic toxicity ameliorative effect, active pre-clinically and/or clinically. Literature survey was carried out by using Google, Scholar Google and Pub-Med. Only the scientific journal articles found on the internet for last two decades were considered. Minerals and semi-synthetic or synthetic analogs of natural products were excluded. Literature study revealed that 34 medicinal plants and 14 natural products exhibited significant protection from arsenic toxicity, mostly in preclinical trials and a few in clinical studies. This research could lead to development of a potentially useful agent in clinical management of arsenicosis in humans.

Choline and Geranate Deep Eutectic Solvent as a Broad-Spectrum Antiseptic Agent for Preventive and Therapeutic Applications.

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Zakrewsky, Michael; Banerjee, Amrita; Apte, Sanjana; Kern, Theresa L; Jones, Mattie R; Sesto, Rico E Del; Koppisch, Andrew T; Fox, David T; Mitragotri, Samir

2016-06-01

Antiseptic agents are the primary arsenal to disinfect skin and prevent pathogens spreading within the host as well as into the surroundings; however the Food and Drug Administration published a report in 2015 requiring additional validation of nearly all current antiseptic agents before their continued use can be allowed. This vulnerable position calls for urgent identification of novel antiseptic agents. Recently, the ability of a deep eutectic, Choline And Geranate (CAGE), to treat biofilms of Pseudomonas aeruginosa and Salmonella enterica was demonstrated. Here it is reported that CAGE exhibits broad-spectrum antimicrobial activity against a number of drug-resistant bacteria, fungi, and viruses including clinical isolates of Mycobacterium tuberculosis, Staphylococcus aureus, and Candida albicans as well as laboratory strains of Herpes Simplex Virus. Studies in human keratinocytes and mice show that CAGE affords negligible local or systemic toxicity, and an ≈180-14 000-fold improved efficacy/toxicity ratio over currently used antiseptic agents. Further, CAGE penetrates deep into the dermis and treats pathogens located in deep skin layers as confirmed by the ability of CAGE in vivo to treat Propionibacterium acnes infection. In combination, the results clearly demonstrate CAGE holds promise as a transformative platform antiseptic agent for preventive as well as therapeutic applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Degradation of Paraoxon and the Chemical Warfare Agents VX, Tabun, and Soman by the Metal-Organic Frameworks UiO-66-NH2, MOF-808, NU-1000, and PCN-777

NARCIS (Netherlands)

Koning, M.C. de; Grol, M. van; Breijaert, T.

2017-01-01

In recent years, Zr-based metal-organic frameworks (MOFs) have been developed that facilitate catalytic degradation of toxic organophosphate agents, such as chemical warfare agents (CWAs). Because of strict regulations, experiments using live agents are not possible for most laboratories and, as a

Degradation of Paraoxon and the Chemical Warfare Agents VX, Tabun, and Soman by the Metal−Organic Frameworks UiO-66-NH2, MOF-808, NU-1000, and PCN-777

NARCIS (Netherlands)

Koning, M.C. de; Grol, M. van; Breijaert, T.C.

2017-01-01

In recent years, Zr-based metal−organic frameworks (MOFs) have been developed that facilitate catalytic degradation of toxic organophosphate agents, such as chemical warfare agents (CWAs). Because of strict regulations, experiments using live agents are not possible for most laboratories and, as a

Environmental levels, toxicity and human exposure to tributyltin (TBT)-contaminated marine environment. a review. b_antizar@hotmail.com.

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Antizar-Ladislao, Blanca

2008-02-01

Tributyltin (TBT) is a toxic chemical used for various industrial purposes such as slime control in paper mills, disinfection of circulating industrial cooling waters, antifouling agents, and the preservation of wood. Due to its widespread use as an antifouling agent in boat paints, TBT is a common contaminant of marine and freshwater ecosystems exceeding acute and chronic toxicity levels. TBT is the most significant pesticide in marine and freshwaters in Europe and consequently its environmental level, fate, toxicity and human exposure are of current concern. Thus, the European Union has decided to specifically include TBT compounds in its list of priority compounds in water in order to control its fate in natural systems, due to their toxic, persistent, bioaccumulative and endocrine disruptive characteristics. Additionally, the International Maritime Organization has called for a global treaty that bans the application of TBT-based paints starting 1 of January 2003, and total prohibition by 1 of January 2008. This paper reviews the state of the science regarding TBT, with special attention paid to the environmental levels, toxicity, and human exposure. TBT compounds have been detected in a number of environmental samples. In humans, organotin compounds have been detected in blood and in the liver. As for other persistent organic pollutants, dietary intake is most probably the main route of exposure to TBT compounds for the general population. However, data concerning TBT levels in foodstuffs are scarce. It is concluded that investigations on experimental toxicity, dietary intake, potential human health effects and development of new sustainable technologies to remove TBT compounds are clearly necessary.

Colon distension and scan protocol for CT-colonography: An overview

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Boellaard, Thierry N., E-mail: t.n.boellaard@amc.uva.nl [Department of Radiology, Academic Medical Center, University of Amsterdam, PB 22660, 1100 DD Amsterdam (Netherlands); Haan, Margriet C. de, E-mail: m.c.dehaan@amc.uva.nl [Department of Radiology, Academic Medical Center, University of Amsterdam, PB 22660, 1100 DD Amsterdam (Netherlands); Venema, Henk W., E-mail: h.w.venema@amc.uva.nl [Department of Radiology, Academic Medical Center, University of Amsterdam, PB 22660, 1100 DD Amsterdam (Netherlands); Department of Biomedical Engineering and Physics, Academic Medical Center, University of Amsterdam, PB 22660, 1100 DD Amsterdam (Netherlands); Stoker, Jaap, E-mail: j.stoker@amc.uva.nl [Department of Radiology, Academic Medical Center, University of Amsterdam, PB 22660, 1100 DD Amsterdam (Netherlands)

2013-08-15

This article reviews two important aspects of CT-colonography, namely colonic distension and scan parameters. Adequate distension should be obtained to visualize the complete colonic lumen and optimal scan parameters should be used to prevent unnecessary radiation burden. For optimal distension, automatic carbon dioxide insufflation should be performed, preferably via a thin, flexible catheter. Hyoscine butylbromide is – when available – the preferred spasmolytic agent because of the positive effect on insufflation and pain/burden and its low costs. Scans in two positions are required for adequate distension and high polyp sensitivity and decubitus position may be used as an alternative for patients unable to lie in prone position. The great intrinsic contrast between air or tagging and polyps allows the use of low radiation dose. Low-dose protocol without intravenous contrast should be used when extracolonic findings are deemed unimportant. In patients suspected for colorectal cancer, normal abdominal CT scan protocols and intravenous contrast should be used in supine position for the evaluation of extracolonic findings. Dose reduction can be obtained by lowering the tube current and/or voltage. Tube current modulation reduces the radiation dose (except in obese patients), and should be used when available. Iterative reconstructions is a promising dose reducing tool and dual-energy CT is currently evaluated for its applications in CT-colonography. This review also provides our institution's insufflation procedure and scan parameters.

Antidotal or protective effects of Curcuma longa (turmeric) and its active ingredient, curcumin, against natural and chemical toxicities: A review.

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Hosseini, Azar; Hosseinzadeh, Hossein

2018-03-01

Curcuma longa is a rhizomatous perennial herb that belongs to the family Zingiberaceae, native to South Asia and is commonly known as turmeric. It is used as herbal remedy due to the prevalent belief that the plant has medical properties. C. longa possesses different effects such as antioxidant, anti-tumor, antimicrobial, anti-inflammatory, wound healing, and gastroprotective activities. The recent studies have shown that C. longa and curcumin, its important active ingredient, have protective effects against toxic agents. In this review article, we collected in vitro and animal studies which are related to protective effects of turmeric and its active ingredient against natural and chemical toxic agents. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Biosynthesis, characterization, and acute toxicity of Berberis tinctoria-fabricated silver nanoparticles against the Asian tiger mosquito, Aedes albopictus, and the mosquito predators Toxorhynchites splendens and Mesocyclops thermocyclopoides.

Science.gov (United States)

Kumar, Palanisamy Mahesh; Murugan, Kadarkarai; Madhiyazhagan, Pari; Kovendan, Kalimuthu; Amerasan, Duraisamy; Chandramohan, Balamurugan; Dinesh, Devakumar; Suresh, Udaiyan; Nicoletti, Marcello; Alsalhi, Mohamad Saleh; Devanesan, Sandhanasamy; Wei, Hui; Kalimuthu, Kandasamy; Hwang, Jiang-Shiou; Lo Iacono, Annalisa; Benelli, Giovanni

2016-02-01

Aedes albopictus is an important arbovirus vector, including dengue. Currently, there is no specific treatment for dengue. Its prevention solely depends on effective vector control measures. In this study, silver nanoparticles (AgNPs) were biosynthesized using a cheap leaf extract of Berberis tinctoria as reducing and stabilizing agent and tested against Ae. albopictus and two mosquito natural enemies. AgNPs were characterized by using UV–vis spectrophotometry, X-ray diffraction, and scanning electron microscopy. In laboratory conditions, the toxicity of AgNPs was evaluated on larvae and pupae of Ae. albopictus. Suitability Index/Predator Safety Factor was assessed on Toxorhynchites splendens and Mesocyclops thermocyclopoides. The leaf extract of B. tinctoria was toxic against larval instars (I–IV) and pupae of Ae. albopictus; LC50 was 182.72 ppm (I instar), 230.99 ppm (II), 269.65 ppm (III), 321.75 ppm (IV), and 359.71 ppm (pupa). B. tinctoria-synthesized AgNPs were highly effective, with LC50 of 4.97 ppm (I instar), 5.97 ppm (II), 7.60 ppm (III), 9.65 ppm (IV), and 14.87 ppm (pupa). Both the leaf extract and AgNPs showed reduced toxicity against the mosquito natural enemies M. thermocyclopoides and T. splendens. Overall, this study firstly shed light on effectiveness of B. tinctoria-synthesized AgNPs as an eco-friendly nanopesticide, highlighting the concrete possibility to employ this newer and safer tool in arbovirus vector control programs.

Influence of Speciation of Thorium on Toxic Effects to Green Algae Chlorella pyrenoidosa

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Can Peng

2017-04-01

Full Text Available Thorium (Th is a natural radioactive element present in the environment and has the potential to be used as a nuclear fuel. Relatively little is known about the influence and toxicity of Th in the environment. In the present study, the toxicity of Th to the green algae Chlorella pyrenoidosa (C. pyrenoidosa was evaluated by algal growth inhibition, biochemical assays and morphologic observations. In the cultural medium (OECD TG 201, Th(NO34 was transformed to amorphous precipitation of Th(OH4 due to hydrolysis. Th was toxic to C. pyrenoidosa, with a 96 h half maximum effective concentration (EC50 of 10.4 μM. Scanning electron microscopy shows that Th-containing aggregates were attached onto the surface of the algal cells, and transmission electron microscopy indicates the internalization of nano-sized Th precipitates and ultrastructural alterations of the algal cells. The heteroagglomeration between Th(OH4 precipitation and alga cells and enhanced oxidative stress might play important roles in the toxicity of Th. To our knowledge, this is the first report of the toxicity of Th to algae with its chemical species in the exposure medium. This finding provides useful information on understanding the fate and toxicity of Th in the aquatic environment.

Toxicity assessment of pesticide triclosan by aquatic organisms and degradation studies.

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Taştan, Burcu Ertit; Tekinay, Turgay; Çelik, Hatice Sena; Özdemir, Caner; Cakir, Dilara Nur

2017-12-01

Triclosan is considered as an important contaminant and is widely used in personal care products as an antimicrobial agent. This study demonstrates the biodegradation of triclosan by two freshwater microalgae and the acute toxicity of triclosan and 2,4-dichlorophenol. The effects of culture media and light on biodegradation of triclosan and the changing morphology of microalgae were systematically studied. Geitlerinema sp. and Chlorella sp. degraded 82.10% and 92.83% of 3.99 mg/L of triclosan at 10 days, respectively. The microalgal growth inhibition assay confirmed absence of toxic effects of triclosan on Chlorella sp., even at higher concentration (50 mg/L) after 72 h exposure. HPLC analysis showed that 2,4-dichlorophenol was produced as degradation product of triclosan by Geitlerinema sp. and Chlorella sp. This study proved to be beneficial to understand biodegradation and acute toxicity of triclosan by microalgae in order to provide aquatic environmental protection. Copyright © 2017 Elsevier Inc. All rights reserved.

Synthesis of silver nanoparticles using a biosurfactant produced in low-cost medium as stabilizing agent

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Charles B.B. Farias

2014-05-01

Conclusions: This process provided a simpler route for nanoparticle synthesis compared to existing systems using whole organisms or partially purified biological extracts, showing that the low-cost biosurfactant can be used for nanoparticle synthesis as a non-toxic and biodegradable stabilizing agent.

Pomalidomide desensitization in a patient hypersensitive to immunomodulating agents

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Seki, J.T.; Sakurai, N.; Lam, W.; Reece, D.E.

2017-01-01

Despite progressive treatments with tandem stem-cell transplantation, patients with incurable myeloma eventually succumb to relapsed or refractory disease if left untreated. Promising agents such as proteasome inhibitors and immunomodulating imide drugs (imids), including the newer-generation agent pomalidomide, in combination with lower-dose dexamethasone, have been shown to be effective and to significantly improve and prolong survival in pretreated patients. Although the incidence of pomalidomide hypersensitivity reaction (hsr) in this class of drugs is not as well known, we have documented cutaneous toxicity (grade 3 by the Common Terminology Criteria for Adverse Events, version 4) in 2 separate cases (not yet published). Because the imids are chemically, structurally, and pharmacologically similar, it is not unreasonable to consider possible cross-reactivity in pomalidomide recipients who developed hsr when receiving previous lines of imids. As a patient’s advocate, it is only prudent to provide a responsible, and yet practical, means to better address cross-sensitivity for patients. Intervention with the use of a rapid desensitization program (rdp) as a preventive measure should be introduced before initiating pomalidomide. Such a proactive measure for the patient’s safety will ensure a smooth transition into pomalidomide treatment. A hsr can be either related or non-related to immunoglobulin E. As imids become an essential treatment backbone for myeloma and other plasma-cell diseases, an increasing number of patients could experience skin and other life-threatening toxicities, resulting in unnecessary discontinuation of these life-prolonging agents. An extemporaneously prepared pomalidomide suspension developed at our centre enables patients to undergo rdp safely. Patients enjoy a good quality of life and clinical response after the rdp procedure. PMID:28874903

Effect of capping agents on the cytotoxicity of silver nanoparticles in human normal and cancer skin cell lines

Energy Technology Data Exchange (ETDEWEB)

Netchareonsirisuk, Ponsawan [Chulalongkorn University, Program in Biotechnology, Faculty of Science (Thailand); Puthong, Songchan [Chulalongkorn University, Antibody Production Research Unit, Institute of Biotechnology and Genetic Engineering (Thailand); Dubas, Stephan [Chulalongkorn University, Petroleum and Petrochemical College (Thailand); Palaga, Tanapat [Chulalongkorn University, Department of Microbiology, Faculty of Science (Thailand); Komolpis, Kittinan, E-mail: kittinan.k@chula.ac.th [Chulalongkorn University, Antibody Production Research Unit, Institute of Biotechnology and Genetic Engineering (Thailand)

2016-11-15

Silver nanoparticles (AgNPs) are among the most widely used nanomaterials in medical and consumer products. However, safety in the uses of AgNPs is still controversial. The toxicity of AgNPs toward various cell types has been reported to depend on the surface properties of the nanoparticles. In this study, the effect of AgNPs with the average size of 5–15 nm on the viability of the CCD-986SK human normal skin fibroblast cell line and A375 human malignant melanoma cell line was evaluated. Comparative toxicity studies, based on MTT assay, were performed by using either sodium alginate or poly (4-styrenesulfonic acid-co-maleic acid) sodium salt (PSSMA) as capping agent in the nanoparticle preparation. The cytotoxicity tests revealed that AgNO{sub 3} alone was highly toxic to both cell types while both alginate and PSSMA alone were not toxic. AgNPs capped with alginate were selectively toxic to the cancer cell line but not to the normal cell line while AgNPs capped with PSSMA were toxic to both cancer and normal cell lines. Judging from the 50 % inhibition concentration (IC{sub 50}), it was found that the cancer cell line was more sensitive to AgNPs than the normal cell line. Study on the mode of cell death by annexin V and propidium iodide staining revealed that AgNPs induced more apoptotic cell death (84–90 %) than necrosis (8–12 %) in the skin cancer cell line. These results suggest that the toxicity of AgNPs depended on the type of capping agent and the type of cell line.

Effectiveness and Safety of Spot Scanning Proton Radiation Therapy for Chordomas and Chondrosarcomas of the Skull Base: First Long-Term Report

International Nuclear Information System (INIS)

Ares, Carmen; Hug, Eugen B.; Lomax, Antony J.; Bolsi, Alessandra; Timmermann, Beate; Rutz, Hans Peter; Schuller, Jan C.; Pedroni, Eros; Goitein, Gudrun

2009-01-01

Purpose: To evaluate effectiveness and safety of spot-scanning-based proton radiotherapy (PT) in skull-base chordomas and chondrosarcomas. Methods and Materials: Between October 1998 and November 2005, 64 patients with skull-base chordomas (n = 42) and chondrosarcomas (n = 22) were treated at Paul Scherrer Institute with PT using spot-scanning technique. Median total dose for chordomas was 73.5 Gy(RBE) and 68.4 Gy(RBE) for chondrosarcomas at 1.8-2.0 Gy(RBE) dose per fraction. Local control (LC), disease specific survival (DSS), and overall survival (OS) rates were calculated. Toxicity was assessed according to CTCAE, v. 3.0. Results: Mean follow-up period was 38 months (range, 14-92 months). Five patients with chordoma and one patient with chondrosarcoma experienced local recurrence. Actuarial 5-year LC rates were 81% for chordomas and 94% for chondrosarcomas. Brainstem compression at the time of PT (p = 0.007) and gross tumor volume >25 mL (p = 0.03) were associated with lower LC rates. Five years rates of DSS and OS were 81% and 62% for chordomas and 100% and 91% for chondrosarcomas, respectively. High-grade late toxicity consisted of one patient with Grade 3 and one patient with Grade 4 unilateral optic neuropathy, and two patients with Grade 3 central nervous system necrosis. No patient experienced brainstem toxicity. Actuarial 5-year freedom from high-grade toxicity was 94%. Conclusions: Our data indicate safety and efficacy of spot-scanning based PT for skull-base chordomas and chondrosarcomas. With target definition, dose prescription and normal organ tolerance levels similar to passive-scattering based PT series, complication-free, tumor control and survival rates are at present comparable.

Modulation of homocysteine toxicity by S-nitrosothiol formation: a mechanistic approach.

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Morakinyo, Moshood K; Strongin, Robert M; Simoyi, Reuben H

2010-08-05

The metabolic conversion of homocysteine (HCYSH) to homocysteine thiolactone (HTL) has been reported as the major cause of HCYSH pathogenesis. It was hypothesized that inhibition of the thiol group of HCYSH by S-nitrosation will prevent its metabolic conversion to HTL. The kinetics, reaction dynamics, and mechanism of reaction of HCYSH and nitrous acid to produce S-nitrosohomocysteine (HCYSNO) was studied in mildly to highly acidic pHs. Transnitrosation of this non-protein-forming amino acid by S-nitrosoglutathione (GSNO) was also studied at physiological pH 7.4 in phosphate buffer. In both cases, HCYSNO formed quantitatively. Copper ions were found to play dual roles, catalyzing the rate of formation of HCYSNO as well as its rate of decomposition. In the presence of a transition-metal ions chelator, HCYSNO was very stable with a half-life of 198 h at pH 7.4. Nitrosation by nitrous acid occurred via the formation of more powerful nitrosating agents, nitrosonium cation (NO(+)) and dinitrogen trioxide (N(2)O(3)). In highly acidic environments, NO(+) was found to be the most effective nitrosating agent with a first-order dependence on nitrous acid. N(2)O(3) was the most relevant nitrosating agent in a mildly acidic environment with a second-order dependence on nitrous acid. The bimolecular rate constants for the direct reactions of HCYSH and nitrous acid, N(2)O(3), and NO(+) were 9.0 x 10(-2), 9.50 x 10(3), and 6.57 x 10(10) M(-1) s(-1), respectively. These rate constant values agreed with the electrophilic order of these nitrosating agents: HNO(2) formation kinetics of HCYSNO. This study has shown that it is possible to modulate homocysteine toxicity by preventing its conversion to a more toxic HTL by S-nitrosation.

The safety of antiangiogenic agents and PARP inhibitors in platinum-sensitive recurrent ovarian cancer.

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Lorusso, Domenica; Fontanella, Caterina; Maltese, Giuseppa; Lepori, Stefano; Tripodi, Elisa; Bogani, Giorgio; Raspagliesi, Francesco

2017-06-01

Recurrence is a common event in endothelial ovarian cancer (EOC) patients, and the choice of the most appropriate treatment is driven by the platinum-free interval, molecular characteristics of the disease such as BRCA mutational status, previous treatments and toxicity. Areas covered: This review focuses on the main hematologic and non-hematologic toxicities correlated with the use of licensed antiangiogenic agents and PARP inhibitors in recurrent platinum-sensitive EOC, providing recommendations for their management. Expert opinion: The clinical research over the next years will be focused on a more precise characterization of molecular pathways underlying tumorigenesis of the five ovarian tumors, to improve the decision-making process in these rare diseases. For this purpose, new study designs and international collaborations will become mandatory. Immunotherapy, antiangiogenic agents and PARP inhibitors will be combined to build a treatment strategy algorithm which will allow patients to receive all the available treatment option, in the more appropriate sequence.

In Search of an Effective in vivo Reactivator for Organophosphorus Nerve Agent-Inhibited Acetylcholinesterase in the Central Nervous System

Science.gov (United States)

2012-01-01

nerve agents, such as sarin (GB), cyclosarin (GF), and VX, are potent inhibitors of the enzyme cholinesterase (ChE). Their toxic effects are due to...three nerve agents. Keywords: acetylcholinesterase; brain; cholinesterase inhibition; cholinesterase reactivation; cyclosarin; diacetylmonoxime...attributed, at least in part, to nuclophilic impedance [Ekstrom et al., 2006a; b; Hoskovcova et al., 2007]. Other AChE- inhibitors , such as soman, become

Reproductive studies with the anti-inflammatory agent, piroxicam: modification of classical protocols.

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Perraud, J; Stadler, J; Kessedjian, M J; Monro, A M

1984-02-14

Reproductive toxicology studies were conducted in rabbits and rats given piroxicam, a non-steroidal anti-inflammatory agent (NSAI), orally at 2, 5 and 10 mg/kg/day. In teratology studies there was neither drug-related embryotoxicity nor teratogenicity. As piroxicam, like other NSAI, affects parturition in rats and leads to a progressive toxicity in lactating females, standard protocols were modified: dams of the female fertility study were treated from 2 weeks prior to mating until day 6 of gestation and females of the post-natal toxicity study were treated from parturition until day 12 of lactation. No other adverse effects on reproduction, fertility and postnatal development were observed.

Acute and subchronic toxicity of the antitumor agent rhodium (II citrate in Balb/c mice after intraperitoneal administration

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Marcella L.B. Carneiro

2015-01-01

Full Text Available This study aimed to investigate potential acute and subchronic toxicity of rhodium (II citrate in female Balb/c mice after intraperitoneal injections. In the acute test, independent groups received five doses; the highest dose (107.5 mg/kg was equivalent to 33 times that used in our previous reports. The other doses were chosen as proportions of the highest, being 80.7 (75%, 53.8 (50%, 26.9 (25% or 13.8 mg/kg (12.5%. Animals were monitored over 38 days and no severe signs of toxicity were observed, according to mortality, monitoring of adverse symptoms, hematological, biochemical and genotoxic parameters. We conclude that the median lethal dose (LD50 could be greater than 107.5 mg/kg. In the subchronic test, five doses of Rh2Cit (80, 60, 40, 20 or 10 mg/kg were evaluated and injections were conducted on alternate days, totaling five applications per animal. Paclitaxel (57.5 mg/kg and saline solution were controls. Clinical observations, histopathology of liver, lung and kidneys and effects on hematological, biochemistry and genotoxic records indicated that Rh2Cit induced no severe toxic effects, even at an accumulated dose up to 400 mg/kg.We suggest Rh2Cit has great potential as an antitumor drug without presenting acute and subchronic toxicity.

Attenuating the toxicity of cisplatin by using selenosulfate with reduced risk of selenium toxicity as compared with selenite

International Nuclear Information System (INIS)

Zhang Jinsong; Peng Dungeng; Lu Hongjuan; Liu Qingliang

2008-01-01

It has been reported that high doses of sodium selenite can reduce side effects of cisplatin (CDDP) without compromising its antitumor activity, thus substantially enhancing the cure rate in tumor-bearing mice. However, the toxicity of selenite at high doses should be a concern. The present study revealed that selenosulfate had much lower toxicity, but possessed equal efficacy in selenium (Se) utilization, as compared with selenite at similar doses when used for the intervention of CDDP. In addition, Se accumulation in whole blood and kidney of mice treated with selenosulfate was highly correlated with the survival rate of mice treated with CDDP (both r > 0.96 and both p < 0.05), suggesting that whole blood Se is a potential clinical biomarker to predict host tolerance to CDDP. In either Se-deficient or -sufficient mice bearing solid tumors of hepatoma 22 (H22), selenosulfate did not disturb the therapeutic effect of CDDP on tumors but effectively attenuated the toxicity of CDDP. Furthermore, in a highly malignant cancer model, with Se-sufficient mice bearing ascitic H22 cells, 8 or 10 mg/kg CDDP alone only achieved a null or 25% cure rate, whereas coadministration of selenosulfate with the above two doses of CDDP achieved cure rates of 87.5% or 75%. These results together argue for consideration of selenosulfate as an agent to enhance the therapeutic efficacy of CDDP

Reactive skin decontamination lotion (RSDL) for the decontamination of chemical warfare agent (CWA) dermal exposure.

Science.gov (United States)

Schwartz, M D; Hurst, C G; Kirk, M A; Reedy, S J D; Braue, E H

2012-08-01

Rapid decontamination of the skin is the single most important action to prevent dermal absorption of chemical contaminants in persons exposed to chemical warfare agents (CWA) and toxic industrial chemicals (TICs) as a result of accidental or intentional release. Chemicals on the skin may be removed by mechanical means through the use of dry sorbents or water. Recent interest in decontamination systems which both partition contaminants away from the skin and actively neutralize the chemical has led to the development of several reactive decontamination solutions. This article will review the recently FDA-approved Reactive Skin Decontamination Lotion (RSDL) and will summarize the toxicity and efficacy studies conducted to date. Evidence of RSDL's superior performance against vesicant and organophosphorus chemical warfare agents compared to water, bleach, and dry sorbents, suggests that RSDL may have a role in mass human exposure chemical decontamination in both the military and civilian arenas.

Opportunities for new CT contrast agents to maximize the diagnostic potential of emerging spectral CT technologies.

Science.gov (United States)

Yeh, Benjamin M; FitzGerald, Paul F; Edic, Peter M; Lambert, Jack W; Colborn, Robert E; Marino, Michael E; Evans, Paul M; Roberts, Jeannette C; Wang, Zhen J; Wong, Margaret J; Bonitatibus, Peter J

2017-04-01

The introduction of spectral CT imaging in the form of fast clinical dual-energy CT enabled contrast material to be differentiated from other radiodense materials, improved lesion detection in contrast-enhanced scans, and changed the way that existing iodine and barium contrast materials are used in clinical practice. More profoundly, spectral CT can differentiate between individual contrast materials that have different reporter elements such that high-resolution CT imaging of multiple contrast agents can be obtained in a single pass of the CT scanner. These spectral CT capabilities would be even more impactful with the development of contrast materials designed to complement the existing clinical iodine- and barium-based agents. New biocompatible high-atomic number contrast materials with different biodistribution and X-ray attenuation properties than existing agents will expand the diagnostic power of spectral CT imaging without penalties in radiation dose or scan time. Copyright © 2016 Elsevier B.V. All rights reserved.

Bladder urotoxicity pathophysiology induced by the oxazaphosphorine alkylating agents and its chemoprevention 

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Łukasz Dobrek

2012-09-01

Full Text Available The use of oxazaphosphorines (cyclophosphamide, ifosfamide in the treatment of numerous neoplastic disorders is associated with their essential adverse effect in the form of hemorrhagic cystitis, which considerably limits the safety and efficacy of their pharmacotherapy. HC is a complex inflammatory response, induced by toxic oxazaphosphorines metabolite – acrolein with subsequent immunocompetetive cells activation and release of many proinflammatory agents. However, there are some chemoprotectant agents which help reduce the HC exacerbation.The article briefly discuses the mechanism of action of oxazaphosphorines, the pathophysiology of the hemorrhagic cystitis development and currently accepted chemopreventive agents, applied to the objective of urotoxicity amelioration. Moreover, the rationale for some phytopharmaceuticals administration as novel bladder protective compounds accompanying cyclophosphamide or ifosfamide therapy was also mentioned. 

The pharmacology and toxicology of three new biologic agents used in pulmonary medicine.

Science.gov (United States)

Albertson, T E; Walby, W F; Allen, R P; Tharratt, R S

1995-01-01

Biological agents have played an important role in the evolution of modern medical therapeutics. Recent advances in biologicals have in part been stimulated by the biotechnology revolution seen over the last several years. Toxicologists need to be aware of the proposed mechanisms and approved and experimental uses of these new biologic agents. Further, controversies about their use, efficacy, cost issues and potential toxicities should be known. Often these drugs are designed for small patient populations thus limiting the availability of human toxicological data bases. This paper reviews the pharmacology and toxicology of three new biologics (recombinant human DNase I, alpha 1-protease inhibitor, and nitric oxide). These agents appear to have important roles in treating specific diseases or disease states seen in pulmonary medicine.

Two unusual causes of peripatellar nonmetastatic positive bone scans in patients with malignancies: case reports

International Nuclear Information System (INIS)

Turner, J.W.; Syed, I.B.; Spencer, R.P.

1976-01-01

Bone scans performed with /sup 99m/Tc-polyphosphate in two patients with epidermoid carcinoma of the lung each showed activity in one knee area. In the first case, radiographs of the area revealed Pellegrini-Stieda calcification over the internal femoral condyle. Uptake corresponded to this process, rather than to a lesion deep in the bone. In the second case, the activity accumulation in the right tibia was the only abnormality noted in the scan. An open biopsy revealed Paget's disease, and no radiographic evidence of Paget's disease was found in any other bone. These cases again illustrate that localized accumulation of a bone-scanning agent, in patients with known primary tumors, does not necessarily denote malignancy in bone

Comparative evaluation of the remineralizing efficacy of calcium sodium phosphosilicate agent and fluoride based on quantitative and qualitative analysis

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Saranya Mony

2015-01-01

Full Text Available Background: Calcium sodium phosphosilicate (NovaMin is an agent that is claimed to release calcium and phosphate ions intraorally to help the self-repair process of enamel. It is used extensively as a desensitizing agent, but the chemical reactions that occur may promote apatite formation enhancing remineralization. The present study was undertaken to evaluate the ability of NovaMin to remineralize an experimentally induced demineralized lesion. The evaluation was done based on the quantitative and qualitative analysis of enamel over the period of 15 and 30 days. Materials and Methods: A sample of 120 noncarious premolar teeth extracted for orthodontic reasons were used for the study. Baseline data for hardness, Ca/PO 4 , and surface characteristics before and after demineralization process was obtained. All the teeth were brushed twice daily at 12 h interval with the test agents using a powered toothbrush for 2 min. The samples were tested on the 15 th and 30 th day. Results: Calcium phosphate ratio and hardness in both the groups improved during the study period. Fluoride group showed higher values for Ca/PO 4 and hardness but was not statistically significant with the P > 0.05. Scanning electron microscope pictures showed that the deposition of the material over the decalcified enamel is more smoother and uniform with NovaMin and more irregular with fluoride. Relevance: NovaMin is found to be as effective in improving the Ca/PO 4 ratio and hardness in a demineralized enamel as fluoride. Hence, it can be a new alternate material for remineralization of enamel with less toxic effects compared to fluorides.

DNA repair: As influenced by age, nutrition, and exposure to toxic substances

International Nuclear Information System (INIS)

Hart, R.; Chou, Ming; Feuers, R.; Leakey, J.; Duffy, P.; Lyn-Cook, B.; Lipman, J.; Makamura, Kenji; Turturro, A.; Allaben, W.

1992-01-01

In evaluating the risk associated with low levels of exposure to toxicants, it is clear that DNA repair, one of the main defenses against agent damage, is not a constant. It can be modified by age, time of day, and physiological state. Nutrition, especially caloric restriction (CR), can modify almost every step in the process of protecting genomic integrity. And history of exposure can modify DNA repair. Thus, the conditions of exposure are almost as important to toxicity as the exposure itself, even at the level of DNA repair. Extrapolation from high to low dose, to be consistent with what is known, should be less a mathematical exercise than an exercise in toxicological judgement, which puts the exposure in proper perspective. This appears to be true at almost every level in the process including a response with a toxic stimulus, even those thought to be very basic, such as DNA repair

Investigating the heterogeneity of alkylating agents' efficacy and toxicity between sexes: A systematic review and meta-analysis of randomized trials comparing cyclophosphamide and ifosfamide (MAIAGE study).

Science.gov (United States)

Fresneau, Brice; Hackshaw, A; Hawkins, D S; Paulussen, M; Anderson, J R; Judson, I; Litière, S; Dirksen, U; Lewis, I; van den Berg, H; Gaspar, N; Gelderblom, H; Whelan, J; Boddy, A V; Wheatley, K; Pignon, J P; De Vathaire, F; Le Deley, M C; Le Teuff, G

2017-08-01

A marginal interaction between sex and the type of alkylating agent was observed for event-free survival in the Euro-EWING99-R1 randomized controlled trial (RCT) comparing cyclophosphamide and ifosfamide in Ewing sarcoma. To further evaluate this interaction, we performed an individual patient data meta-analysis of RCTs assessing cyclophosphamide versus ifosfamide in any type of cancer. A literature search produced two more eligible RCTs (EICESS92 and IRS-IV). The endpoints were progression-free survival (PFS, main endpoint) and overall survival (OS). The hazard ratios (HRs) of the treatment-by-sex interaction and their 95% confidence interval (95% CI) were assessed using stratified multivariable Cox models. Heterogeneity of the interaction across age categories and trials was explored. We also assessed this interaction for severe acute toxicity using logistic models. The meta-analysis comprised 1,528 pediatric and young adult sarcoma patients from three RCTs: Euro-EWING99-R1 (n = 856), EICESS92 (n = 155), and IRS-IV (n = 517). There were 224 PFS events in Euro-EWING99-R1 and 200 in the validation set (EICESS92 + IRS-IV), and 171 and 154 deaths in each dataset, respectively. The estimated treatment-by-sex interaction for PFS in Euro-EWING99-R1 (HR = 1.73, 95% CI = 1.00-3.00) was not replicated in the validation set (HR = 0.97, 95% CI = 0.55-1.72), without heterogeneity across trials (P = 0.62). In the pooled analysis, the treatment-by-sex interaction was not significant (HR = 1.31, 95% CI = 0.89-1.95, P = 0.17), without heterogeneity across age categories (P = 0.88) and trials (P = 0.36). Similar results were observed for OS. No significant treatment-by-sex interaction was observed for leucopenia/neutropenia (P = 0.45), infection (P = 0.64), or renal toxicity (P = 0.20). Our meta-analysis did not confirm the hypothesis of a treatment-by-sex interaction on efficacy or toxicity outcomes. © 2017 Wiley Periodicals, Inc.

Contrast-enhanced peripheral MRA. Technique and contrast agents

International Nuclear Information System (INIS)

Nielsen, Yousef W.; Thomsen, Henrik S.

2012-01-01

In the last decade contrast-enhanced magnetic resonance angiography (CE-MRA) has gained wide acceptance as a valuable tool in the diagnostic work-up of patients with peripheral arterial disease. This review presents current concepts in peripheral CE-MRA with emphasis on MRI technique and contrast agents. Peripheral CE-MRA is defined as an MR angiogram of the arteries from the aortic bifurcation to the feet. Advantages of CE-MRA include minimal invasiveness and lack of ionizing radiation. The basic technique employed for peripheral CE-MRA is the bolus-chase method. With this method a paramagnetic MRI contrast agent is injected intravenously and T1-weighted images are acquired in the subsequent arterial first-pass phase. In order to achieve high quality MR angiograms without interfering venous contamination or artifacts, a number of factors need to be taken into account. This includes magnetic field strength of the MRI system, receiver coil configuration, use of parallel imaging, contrast bolus timing technique, and k-space filling strategies. Furthermore, it is possible to optimize peripheral CE-MRA using venous compression techniques, hybrid scan protocols, time-resolved imaging, and steady-state MRA. Gadolinium(Gd)-based contrast agents are used for CE-MRA of the peripheral arteries. Extracellular Gd agents have a pharmacokinetic profile similar to iodinated contrast media. Accordingly, these agents are employed for first-pass MRA. Blood-pool Gd-based agents are characterized by prolonged intravascular stay, due to macromolecular structure or protein binding. These agents can be used for first-pass, as well as steady-state MRA. Some Gd-based contrast agents with low thermodynamic stability have been linked to development of nephrogenic systemic fibrosis in patients with severe renal insufficiency. Using optimized technique and a stable MRI contrast agent, peripheral CE-MRA is a safe procedure with diagnostic accuracy close to that of conventional catheter X

Pelletized ponderosa pine bark for adsorption of toxic heavy metals from water

Science.gov (United States)

Miyoung Oh; Mandla A. Tshabalala

2007-01-01

Bark flour from ponderosa pine (Pinus ponderosa) was consolidated into pellets using citric acid as cross-linking agent. The pellets were evaluated for removal of toxic heavy metals from synthetic aqueous solutions. When soaked in water, pellets did not leach tannins, and they showed high adsorption capacity for Cu(ll), Zn(ll), Cd(ll). and Ni(ll) under both equilibrium...

Supercapacitive transport of pharmacologic agents using nanoporous gold electrodes.

Science.gov (United States)

Gittard, Shaun D; Pierson, Bonnie E; Ha, Cindy M; Wu, Chung-An Max; Narayan, Roger J; Robinson, David B

2010-02-01

In this study, nanoporous gold supercapacitors were produced by electrochemical dealloying of gold-silver alloy. Scanning electron microscopy and energy dispersive X-ray spectroscopy confirmed completion of the dealloying process and generation of a porous gold material with approximately 10 nm diameter pores. Cyclic voltammetry and chronoamperometry of the nanoporous gold electrodes indicated that these materials exhibited supercapacitor behavior. The storage capacity of the electrodes measured by chronoamperometry was approximately 3 mC at 200 mV. Electrochemical storage and voltage-controlled delivery of two model pharmacologic agents, benzylammonium and salicylic acid, was demonstrated. These results suggest that capacitance-based storage and delivery of pharmacologic agents may serve as an alternative to conventional drug delivery methods.

Anti-herpesvirus agents: a patent and literature review (2003 to present).

Science.gov (United States)

Skoreński, Marcin; Sieńczyk, Marcin

2014-08-01

The standard therapy used to treat herpesvirus infections is based on the application of DNA polymerase inhibitors such as ganciclovir or aciclovir. Unfortunately, all of these compounds exhibit relatively high toxicity and the mutation of herpesviruses results in the appearance of new drug-resistant strains. Consequently, there is a great need for the development of new, effective and safe anti-herpesvirus agents that employ different patterns of therapeutic action at various stages of the virus life cycle. Patents and patent applications concerning the development of anti-herpesvirus agents displaying different mechanisms of action that have been published since 2003 are reviewed. In addition, major discoveries in this field that have been published in academic papers have also been included. Among all the anti-herpesvirus agents described in this article, the inhibitors of viral serine protease seem to present one of the most effective/promising therapeutics. Unfortunately, the practical application of these antiviral agents has not yet been proven in any clinical trials. Nevertheless, the dynamic and extensive work on this subject gives hope that a new class of anti-herpesvirus agents aimed at the enzymatic activity of herpesvirus serine protease may be developed.

A new contrast agent for radiological and dissection studies of the arterial network of anatomic specimens.

Science.gov (United States)

Bulla, A; Casoli, C; Farace, F; Mazzarello, V; De Luca, L; Rubino, C; Montella, A

2014-01-01

The aim of the present study is to propose a new contrast agent that can be easily applied both to CT and dissection studies to replace lead oxide based formulas for comparative anatomical analyses of the vascularisation of cadaveric specimens. The infusion material was an epoxy resin, especially modified by the addition of barium sulphate to enhance its radiopacity. The final copolymer was toxicologically safe. To test the properties of the new material, several cadaveric limb injections were performed. The injected specimens were both CT scanned to perform 3D vascular reconstructions and dissected by anatomical planes. There was a perfect correspondence between the image studies and the dissections: even the smallest arteries on CT scan can be identified on the specimen and vice versa. The properties of the epoxy allowed an easy dissection of the vessels. The new imaging techniques available today, such as CT scan, can evaluate the vascular anatomy in high detail and 3D. This new contrast agent may help realising detailed vascular studies comparing CT scan results with anatomical dissections. Moreover, it may be useful for teaching surgical skills in the field of plastic surgery.

False positive and false negative FDG-PET scans in various thoracic diseases

International Nuclear Information System (INIS)

Chang, Jung Min; Lee, Hyun Ju; Goo, Jin Mo; Lee, Ho Young; Lee, Jong Jin; Chung, June Key; Im, Jung Gi

2006-01-01

Fluorodeoxygucose (FDG)-positron emission tomography (PET) is being used more and more to differentiate benign form malignant focal lesions and it has been shown to be more efficacious than conventional chest computed tomography (CT). However, FDG is not a cancer-specific agent, and false positive findings in benign diseases have been reported. Infectious diseases (mycobacterial, fungal, bacterial infection), sarcoidosis, radiation pneumonitis and post-operative surgical conditions have shown intense uptake on PET scan. On the other hand, tumors with low glycolytic activity such as adenomas, bronchioloalveolar carcinomas, carcinoid tumors, low grade lymphomas and small sized tumors have revealed false negative findings on PET scan, Furthermore, in diseases located near the physiologic uptake sites (heart, bladder, kidney, and liver), FDG-PET should be complemented with other imaging modalities to confirm results and to minimize false negative findings. Familiarity with these false positive and negative findings will help radiologists interpret PET scans more accurately and also will help to determine the significance of the findings. In this review, we illustrate false positive and negative findings of PET scan in a variety of diseases

Studying antimicrobial-induced morphostructural damage of bacteria by Scanning Electron Microscope

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Shruti Shukla

2015-12-01

Full Text Available In this investigation, a scanning electron microscopy (SEM method was used to examine the morphostructural changes in bacterial cells induced by antimicrobial agents. SEM-based visual approach is referred the study of bacterial cells and their physiological consequences when affected by antibiotics or antibacterial agents permitting the observation of characteristic morphological defects of cell wall, and provides valuable insights into processes involved in bacterial cell death. This experiment visualized various step-by-step techniques used in the slide preparation of bacterial cells treated with specific antimicrobial agent for analyzing the morphological alterations such as increase of cell wall roughness, cell disruption, cell swelling and lysed cell formation due to loss of intracellular material using SEM analysis when compared with untreated normal cells as a control. The SEM approach used in this visual experiment may analyze the antimicrobial effect of any commercially known or new compounds in a very conducive manner.

Thyroid cancer in toxic and non-toxic multinodular goiter

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Cerci C

2007-01-01

Full Text Available Background : Many authors have claimed that hyperthyroidism protects against thyroid cancer and believed that the incidence of malignancy is lower in patients with toxic multinodular goiter (TMG than in those with non-toxic multinodular goiter. But in recent studies, it was reported that the incidence of malignancy with TMG is not as low as previously thought. Aim : To compare the thyroid cancer incidence in patients with toxic and non-toxic multinodular goiter. Settings and Design : Histology reports of patients treated surgically with a preoperative diagnosis of toxic and non-toxic multinodular goiter were reviewed to identify the thyroid cancer incidence. Patients having a history of neck irradiation or radioactive iodine therapy were excluded from the study. Materials and Methods : We reviewed 294 patients operated between 2001-2005 from toxic and non-toxic multinodular goiter. One hundred and twenty-four of them were toxic and 170 were non-toxic. Hyperthyroidism was diagnosed by elevated tri-iodothyroinine / thyroxine ratios and low thyroid-stimulating hormone with clinical signs and symptoms. All patients were evaluated with ultrasonography and scintigraphy and fine needle aspiration biopsy. Statistical Analysis Used : Significance of the various parameters was calculated by using ANOVA test. Results : The incidence of malignancy was 9% in the toxic and 10.58% in the non-toxic multinodular goiter group. Any significant difference in the incidence of cancer and tumor size between the two groups could not be detected. Conclusions : The incidence of malignancy in toxic multinodular goiter is not very low as thought earlier and is nearly the same in non-toxic multinodular goiter.