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At least 127 records · Page 7Linked to original sources
PubMed2006

Effects of depleted uranium after short-term exposure on vitamin D metabolism in rat.

Uranium is a natural radioactive heavy metal. Its toxicity has been demonstrated for different organs, including bone, kidney, liver and brain. Effects of an acute contamination by depleted uranium (DU) were investigated in vivo on vitamin D(3) biosynthetic pathway. Rats received an intragastric administration of DU (204 mg/kg) and various parameters were studied either on day 1 or day 3 after contamination. Cytochrome P450 (CYP27A1, CYP2R1, CYP27B1, CYP24A1) enzymes involved in vitamin D metabolism and two vitamin D(3)-target genes (ECaC1, CaBP-D9K) were assessed by real time RT-PCR in liver and kidneys. CYP27A1 activity was measured in liver and vitamin D and parathyroid hormone (PTH) level were measured in plasma. In acute treated-rats, vitamin D level was increased by 62% and decreased by 68% in plasma, respectively at day 1 and at day 3, which paralleled with a concomitant decrease of PTH level (90%) at day 3. In liver, cyp2r1 mRNA level was increased at day 3. Cyp27a1 activity decreased at day 1 and increased markedly at day 3. In kidney, cyp27b1 mRNA was increased at days 1 and 3 (11- and 4-fold respectively). Moreover, ecac1 and cabp-d9k mRNA levels were increased at day 1 and decreased at day 3. This work shows for the first time that DU acute contamination modulates both activity and expression of CYP enzymes involved in vitamin D metabolism in liver and kidney, and consequently affects vitamin D target genes levels.

Animals↗
PubMed1977

Quantitative analysis of macrophage phagocytosis by uptake of particulate 192iridium.

This study describes a method for the quantitation of macrophage phagocytosis by measuring the uptake of small particles of the radioactive inert metal, iridium (192Ir). It is shown that macrophage labeling with 192Ir was uniform, and the label was retained by the macrophages up to 21 days post-plating (when all cultures were terminated). 192Ir labeled macrophages were able to phagocytose other particles such as sheep red blood cells and were able to be activated to become tumorcidal in vitro 21 days following initial 192Ir uptake. Therefore, 192Ir could be a useful tool for the quantitative analysis and correlation of phagocytosis, tumor cytotoxicity and other macrophage functions.

Animals↗
PubMed1988

Synthesis of diethylenetriaminepentaacetic acid conjugated inulin and utility for cellular uptake of liposomes.

The synthesis, binding of radioactive cations, liposomal encapsulation, and biodistribution of the oxidized-inulin reaction product with ethylenediamine and diethylenetriaminepentaacetic acid (4) are described. The four-step synthesis of the inulin derivative proceeded in a good overall yield of 72%. The complex of the inulin derivative with either 67Ga3+ or 111In3+ was stable in vivo and did not readily distribute into tissues, being excreted primarily in urine after intravenous administration to mice. The liposome-entrapped inulin derivative can be loaded with radioactive heavy metal cations by mobile ionophores in high radiochemical yields of 80-91%. Following the intravenous administration of the liposomal encapsulation of the indium-111-labeled inulin derivative, the entrapped compound had a biodistribution characteristic of liposomes and allowed an estimation of the extent of the intracellular uptake of liposomes. The ability of the inulin derivative to chelate many different types of metals will allow the use of this probe for studying subtle differences in tissue distribution resulting from different drug targeting or delivery protocols in the same animal by multiple labeling techniques. Moreover, the chelate-conjugated inulin permits studies of the applications of drug delivery systems in primates or human subjects by noninvasive techniques such as gamma-scintigraphic or nuclear magnetic resonance imaging methods.

Animals↗
PubMed2003

Uranyl acetate causes DNA single strand breaks in vitro in the presence of ascorbate (vitamin C).

Uranium is a radioactive heavy metal with isotopes that decay on the geological time scale. People are exposed to uranium through uranium mining, processing, the resulting mine tailings, and the use of depleted uranium in the military. Acute exposures to uranium are chemically toxic to the kidney; however, little is known about chronic exposures, for example, if there is a direct chemical genotoxicity of uranium. The hypothesis that is being tested in the current work is that hexavalent uranium, as uranyl ion, may have a chemical genotoxicity similar to that of hexavalent chromium. In the current study, reactions of uranyl acetate (UA) and ascorbate (vitamin C) were observed to produce plasmid relaxation in pBluescript DNA. DNA strand breaks increased with increasing concentrations of a 1:1 reaction of UA and ascorbate but were not affected by increasing the ratio of ascorbate. Plasmid relaxation was inhibited by coincubation of reactions with catalase but not by coincubation with the radical scavengers mannitol, sodium azide, or 5,5-dimethyl-1-pyrroline-N-oxide. Reactions of UA and ascorbate monitored by (1)H NMR spectroscopy showed formation of a uranyl ascorbate complex, with no evidence of a dehydroascorbate product. A previous study inferred that hydroxyl radical formation was responsible for oxidative DNA damage in the presence of reactions of uranyl ion, hydrogen peroxide, and ascorbate [Miller et al. (2002) J. Bioinorg. Chem. 91, 246-252]. Current results, in the absence of added hydrogen peroxide, were not completely consistent with the interpretation that strand breaks were produced by a Fenton type generation of reactive oxygen species. Data were also consistent with the interpretation that a uranyl ascorbate complex was catalyzing hydrolysis of the DNA-phosphate backbone, in a manner similar to that known for the lanthanides. These data suggest that uranium may be directly genotoxic and may, like chromium, react with DNA by more than one pathway.

Ascorbic Acid↗
PubMed2005

Remediation of contaminated soils using supercritical fluid extraction: a review (1994-2004).

Considerable effort is being made to remediate soils contaminated with petroleum hydrocarbons, polyaromatic hydrocarbons, polychlorinated biphenyls, dioxins, heavy metals and other organic and inorganic compounds that have resulted from industrial activities, accidental spills and improper waste disposal practices. Current remediation technologies may be limited when treating certain types of contaminated soils and therefore new, efficient and cost effective technologies are being investigated. Supercritical fluid extraction is a potential remediation technology for contaminated soils. It is a simple, fast and selective solvent extraction process that uses a supercritical fluid as the solvent. A commonly used fluid is carbon dioxide at pressures and temperatures greater than 7.4 MPa and 31 degrees C, respectively. In supercritical fluid extraction, the extracted contaminants first dissolve into the supercritical solvent and then these contaminants are separated from the supercritical solvent via a simple change in pressure and temperature conditions or by using a separation process. This paper provides a review of supercritical fluid extraction and its application to the remediation of contaminated soils. This review focuses on the removal of organic contaminants (such as petroleum hydrocarbons, polyaromatic hydrocarbons, polychlorinated biphenyls and others) and inorganic contaminants (such as heavy metals and radioactive elements) from soils. Recent data (1994-2004) on the supercritical fluid extraction of spiked soils and field-contaminated soils were collected. The success of supercritical fluid extraction as a method for removing these contaminants from soils is highlighted and some of the future research needed to develop it as a commercial-scale economic remediation technology are discussed.

Chromatography, Supercritical Fluid↗
PubMed1999

Elevated urine uranium excretion by soldiers with retained uranium shrapnel.

The use of depleted uranium in munitions has given rise to a new exposure route for this chemically and radioactively hazardous metal. A cohort of U.S. soldiers wounded while on or in vehicles struck by depleted uranium penetrators during the Persian Gulf War was identified. Thirty-three members of this cohort were clinically evaluated, with particular attention to renal abnormalities, approximately 3 y after their injury. The presence of retained shrapnel was identified by x ray, and urine uranium concentrations were measured on two occasions. The absorption of uranium from embedded shrapnel was strongly suggested by measurements of urine uranium excretion at two time intervals: one in 1993/1994 and one in 1995. Mean urine uranium excretion was significantly higher in soldiers with retained shrapnel compared to those without shrapnel at both time points (4.47 vs. 0.03 microg g(-1) creatinine in 1993/1994 and 6.40 vs. 0.01 microg g(-1) creatinine in 1995, respectively). Urine uranium concentrations measured in 1995 were consistent with those measured in 1994/1993, with a correlation coefficient of 0.9. Spot urine measurements of uranium excretion were also well correlated with 24-h urine collections (r = 0.95), indicating that spot urine samples can be reliably used to monitor depleted uranium excretion in the surveillance program for this cohort of soldiers. The presence of uranium in the urine can be used to determine the rate at which embedded depleted uranium fragments are releasing biologically active uranium ions. No evidence of a relationship between urine uranium excretion and renal function could be demonstrated. Evaluation of this cohort continues.

Amputation, Surgical↗
PubMed1985

Extraction efficiency and biliary excretion of hepatobiliary imaging agents in the rat perfused liver.

A multitude of transitional metal complexes has recently been introduced into clinical practice as hepatobiliary imaging agents; the kinetics of these substances are often poorly understood. To gain better insight into characteristics of these different agents, we measured the extraction efficiency and mean biliary transit time of a variety of iminodiacetate derivatives in the in-situ rat perfused liver. First pass hepatic extraction efficiency averaged 59% for 99mTc N-(p-isopropylacetanilide) iminodiacetate, 73% for 99mTc N-(2,6-diethylacetanilide) iminodiacetate, 74% for 99mTc N-(3-bromo-2,4,6-trimethylacetanilide) iminodiacetate, 90% for 99mTc N-(p-butylacetanilide) iminodiacetate, and 93% for 99mTc N-pyridoxyl-5-methyltryptophan. By comparison, extraction of another organic anionic compound, 131I Rose bengal, was only 12.4%. Mean hepatocyte transit times varied from 2.3 to 7.5 min. Shorter mean transit times were observed for diortho substituted and longer mean transit times for para substituted metal complexes. Radioactivity was quantitatively recovered in bile, and excretion kinetics overall were consistent with data generated in whole animals. These studies demonstrate the value of the in-situ rat perfused liver as a screening tool to characterize hepatobiliary imaging agents.

Animals↗
PubMed2006

Engineering of Deinococcus radiodurans R1 for bioprecipitation of uranium from dilute nuclear waste.

Genetic engineering of radiation-resistant organisms to recover radionuclides/heavy metals from radioactive wastes is an attractive proposition. We have constructed a Deinococcus radiodurans strain harboring phoN, a gene encoding a nonspecific acid phosphatase, obtained from a local isolate of Salmonella enterica serovar Typhi. The recombinant strain expressed an approximately 27-kDa active PhoN protein and efficiently precipitated over 90% of the uranium from a 0.8 mM uranyl nitrate solution in 6 h. The engineered strain retained uranium bioprecipitation ability even after exposure to 6 kGy of 60Co gamma rays. The PhoN-expressing D. radiodurans offers an effective and eco-friendly in situ approach to biorecovery of uranium from dilute nuclear waste.

Acid Phosphatase↗
PubMed2003

Deaths from neoplasms and detection of radionuclides in excised human lungs in the Eordea Basin, Greece.

Lignite contains various trace-metal natural radioactive contaminants. In the Eordea Basin, the most important lignite field in Greece, the authors conducted a proportional mortality ratio (PMR) study that compared the mortality rates of individuals who lived in the basin vs. a control group who resided in the city of Kilkis, over a 30-yr period. The following information was used in the study: (a) municipal registrations of deaths from neoplasms during the period from 1971 to 2000, and (b) detection of radioactive substances in samples obtained from excised lungs of individuals living in Eordea Basin who suffered from neoplasm. The corresponding registrations of deaths from neoplasm of the inhabitants of Kilkis, a city located outside the Eordea Basin, formed the control group. A diachronic increase of the PMR was detected as a result of neoplasms and, particularly, as a result of lung cancer in Eordea Basin. However, the above ratio did not exceed the corresponding PMR recorded in Kilkis. In 20 lung samples obtained from patients who had lived in Eordea Basin, and in 19 lung samples from patients in Kilkis, the activity of the radionuclides of uranium and thorium radioactive decay series, potassium-40, and cesium-137 was not higher than expected. No statistically significant difference was found between the inhabitants of the 2 regions, thus it was concluded that the increase in respiratory-system neoplasms was likely associated with the high prevalence of smoking among the regions' inhabitants. In future studies, a longer observation period and examination of more cases will be necessary to further investigate a possible association between radionuclides and lung neoplasms in the Eordea Basin.

Aged↗
PubMed1977

Characteristics of modulators and substrates binding to rat liver adenylate kinase.

The binding of adenine nucleotides to liver adenylate kinase was dependent on Mg2+ ions. Citric acid enhanced the binding of all metal-chelated radioactive nucleotides and indicated two observable binding sites for Mg3H-ADP and Mg3-ATP and one-half binding site for Mg3H-AMP. Two binding sites of Mg3H-ADP and one binding site for Mg3H-ATP were also observed in the absence of citric acid. Stoichiometric binding of 14C-citric acid to liver adenylate kinase varied with additions of different nucleotides. AMP prevented whereas ADP and ATP enhanced the binding of 14C-citric acid.

Adenosine Diphosphate↗
PubMedDate not supplied

Methodology for selecting substances for the National Exposure Registry.

The National Exposure Registry was created in response to the pervasiveness of chemical contamination at the nation's waste sites and the relative lack of information on human health outcomes associated with long-term, low-level exposure to most of these substances. A ranking scheme was developed by the Agency for Toxic Substances and Disease Registry (ATSDR) to select the substances for which substance-specific subregistries of the National Exposure Registry would be developed. This scheme uses a general decision analysis approach that incorporates the most relevant and up-to-date data available on the substances found at sites known to ATSDR. There are currently four general subregistries (volatile organic compounds, dioxins, heavy metals, and radioactive substances) made up of persons exposed to specific primary contaminants, as selected by means of this ranking scheme.

Data Collection↗
PubMed2005

Environmental impacts of cooling system on Abou Qir Bay.

This study was conducted to evaluate the impacts of cooling water on cooling system of Abou Qir Power Plant and on the receiving Abou Qir Bay. Abou Qir Power Plant is a conventional steam electric power plant located in Alexandria Governorate, Egypt. Water and biota samples were collected monthly from cooling water and Abou Qir Bay over a year. Heavy metals, radionuclide, anions and total hydrocarbons were analyzed in the samples using Instrumental Neutron Activation Analysis (INAA), Gamma-ray Spectrometry (GS), Ion Selective Electrodes (ISE) and Gas Chromatography (GC). The results revealed that the characteristics of inlet cooling water had a tendency to be corrosive to the cooling system. The outlet cooling water complied with Environmental Law 4/1994 in all measured parameters except phosphate, ammonia and total petroleum hydrocarbons. On the other hand, samples from all sites had the lowest annual total count of algae in winter and highest count during summer. There are -ve correlations between algae and heavy metals, hydrocarbons, and radioactivity. Algae correlated highly significantly (p<0.01) with Pb, Cu, Ni, total petroleum hydrocarbons, dissolved petroleum hydrocarbon and uranium. Anabaena Sp. (blue green algae) and Euglina Sp.(flagellate) had highly significant (p<0.01) -ve correlation with heavy metals and natural radioactivity. The accumulation percentage of heavy metals by algae ranged from 22% to 37%, and the highest percent was for uranium and the lowest was for chromium. It is recommended to optimize the addition of polyphosphate inhibitor at inlet cooling water to inhibit corrosion in the cooling system and to avoid increase of Anabaena Sp. in the outlet, and to avoid enhancing algae growth that has a great tendency to accumulate heavy metals, and good housekeeping to avoid oil spills containing hydrocarbons from the power plant to sea water.

Chromatography, Gas↗
PubMedDate not supplied

N-(iodoacetyl)-p-phenylenediamine-EDTA: a reagent for high-efficiency incorporation of an EDTA-metal complex at a rationally selected site within a protein.

We have developed a highly efficient procedure to incorporate an EDTA:metal complex at a rationally selected site within a full-length protein. Our procedure has two steps: In step one, we use site-directed mutagenesis to introduce a unique solvent-accessible cysteine residue at the site of interest. In step two, we derivatized the resulting protein with N-(iodoacetyl)-p-phenylenediamine-EDTA:metal, a novel haloacetyl derivative of EDTA:metal. We have used this procedure to incorporate each of three EDTA:metal complexes at amino acid 2 of the helix-turn-helix motif of the sequence-specific DNA binding protein Cro: a radioactive and nucleolytic EDTA:metal complex (EDTA:55Fe), a radioactive EDTA:metal complex (EDTA:63Ni), and a fluorescent and heavy-atom EDTA:metal complex (EDTA:Eu). Incorporation of EDTA:metal was highly efficient (> 80% for EDTA:55Fe and EDTA:63Ni; 60% for EDTA:Eu) and highly site-specific (> 99%). We have analyzed DNA affinity cleaving by the Cro derivative having EDTA:55Fe at amino acid 2 of the helix-turn-helix motif. The Cro derivative cleaves DNA at base pairs -4 to 6 of the DNA half site in the protein-DNA complex, indicating that amino acid 2 of the helix-turn-helix motif of Cro is close to base pairs -4 to 6 of the DNA half site in the Cro-DNA complex in solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteriophage lambda↗
PubMed1981

Environmental biochemistry of current environmental levels of heavy metals: preparation of radiotracers with very high specific radioactivity for metallobiochemical experiments on laboratory animals.

Environmental toxicology research on dose-response relationships of heavy metals requires experiments on laboratory animals exposed to "low doses" of trace elements which should reflect "present or actual environmental levels" characteristic of polluted environments. Unfortunately no criteria exist to establish the "low doses" to which laboratory animals must be exposed, in practice the choice of the level used is made in an almost arbitrary manner. In order to define the "present environmental levels" of heavy metals which should be administered to laboratory animals an approach is suggested, based upon knowledge of the concentrations of trace elements in the diet, air and food as well as the fractions absorbed. Today daily intakes of trace elements by man are of the order of few micrograms or nanograms thus requiring the use of extremely sensitive analytical techniques to determine the very low amounts of heavy metals in tissues and cellular components. In these fields of research the use of radiotracers with very high specific radioactivity appears particularly advantageous but requires considerable care during their preparation and use. The first part of this paper deals with a definition of the ranges of concentrations of trace elements which should be used for metabolic studies on laboratory animals when they are exposed via different routes such as ingestion, inhalation in injection; the second part describes the production of radiotracers with very high specific radioactivity by proton activation in the cyclotron and by neutron irradiation in the nuclear reactor. Their use to label present levels of heavy metals under conditions adapted for biochemical purposes, as well as the preparation of different metal-labelled chemical species is also reported. Particular attention is directed to quality control of the radiotracer solutions which are administered to the animals including those of radioactivity concentrations, radioisotopic purity, radiochemical purity, carrier content and chemical impurities.

Animals↗
PubMed1999

Nucleotide variation in the p53 tumor-suppressor gene of voles from Chernobyl, Ukraine.

The 1986 Chernobyl disaster contaminated vast regions of Ukraine and Belarus with a variety of radioactive isotopes and heavy metals. While over 90% of the radioactive isotopes have decayed into stable compounds, radiation levels in contaminated areas are still extraordinarily high. In fact, some rodents living near the reactor have internal 134,137Cs concentrations approaching 80 000 Bq/g. Several recent genetic analyses of vertebrates have illustrated that mutation rates of organisms exposed to radiation from Chernobyl are higher than in control groups, but none have studied DNA sequences. Nucleotide sequences of rodent mitochondrial genes were originally reported to have been hypervariable, but those results were subsequently retracted. Herein, I report the results of a pilot study to determine the extent of nucleotide variation at the p53 gene in four species of rodents (voles) from Chernobyl and from control sites. I sequenced a 788 bp region (coding and non-coding) of p53 in 30 different mice comprising four different species of Microtus. Nucleotide variation at the population level was due to deletions and substitutions; both were limited to introns. There were no significant differences between the number of haplotypes in radioactive and control populations (p=0.60). Rare or private alleles might have arisen due to unique mutational pressures at Chernobyl. Alternatively, natural selection might have favored one allele over others (i.e., a selective sweep). Neither scenario is strongly supported by these data. Thus, no apparent genetic effects of the Chernobyl disaster on the p53 gene of resident voles were revealed; more extensive surveys will be necessary to determine if mutation rates are indeed elevated in mice from Chernobyl. However, two salient points emerge; the first involves the utility of introns as markers for mutations in coding regions and the second considers the relative merits of cloning in mutation detection studies.

Animals↗