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PubMed1987

Inhibition of the catalytic subunit of cAMP-dependent protein kinase by dicyclohexylcarbodiimide.

The hydrophobic carbodiimide dicyclohexylcarbodiimide (DCCD) has been shown to inhibit the catalytic (C) subunit of adenosine cyclic 3',5'-phosphate dependent protein kinase (EC 2.7.1.3) in a time-dependent, irreversible manner. The rate of inactivation was first order and showed saturation kinetics with an apparent Ki of 60 microM. Magnesium adenosine 5'-triphosphate (MgATP) was capable of protecting against this inhibition, whereas neither a synthetic peptide substrate nor histone afforded protection. Mg alone afforded some protection. When the catalytic subunit was aggregated with the regulatory subunit in the holoenzyme complex, no inhibition was observed. The inhibition was enhanced at low pH, suggesting that a carboxylic acid group was the target for interaction with DCCD. On the basis of the protection studies, it is most likely that this carboxylic acid group is associated with the MgATP binding site, perhaps serving as a ligand for the metal. Efforts to identify the site that was modified by DCCD included (1) modification with [14C]DCCD, (2) modification by DCCD in the presence of [3H]aniline, and (3) modification with DCCD and [14C]glycine ethyl ester. In no case was radioactivity incorporated into the protein, suggesting that the irreversible inhibition was due to an intramolecular cross-link between a reactive carboxylic acid group and a nearby amino group. Differential peptide mapping identified a single peptide that was consistently lost as a consequence of DCCD inhibition. This peptide (residues 166-189) contained four carboxylic acid residues as well as an internal Lys.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1982

The effects of lysine-vasopressin on hemodynamics during early post burn period in pigs.

In order to investigate the central and peripheral circulatory effects of a vasoactive drug, lysin vasopressin (LVP), in the early postburn period, 18 piglets were submitted to an experimental study. Anaesthesia was performed by thiopentone sodium as i.v. infusion and mechanically controlled ventilation via endotracheal intubation. Burn injury was brought about by heated metal stamps applied to the back and sides of the animals causing a full thickness skin burn corresponding to 32-35% of the total body surface area. Cardiac output decreased significantly after burn and so did organ blood flow, measured with radioactively labelled microspheres, especially after 4 hours. LVP-infusion did not further decrease cardiac output after burn but decreased the blood flow to the skin, carcass and proximal gastrointestinal tract. The liver perfusion was increased, while the flow in the other organs was not different from that in burned pigs not given LVP. The therapeutical implications are discussed.

Animals↗
PubMed1995

Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) (Cu-PTSM), a metal complex with selective NADH-dependent reduction by complex I in brain mitochondria: a potential radiopharmaceutical for mitochondria-functional imaging with positron emission tomography (PET).

The reductive retention mechanism of copper(II)-pyruvaldehyde-bis (N4-methylthiosemicarbazone) (Cu-PTSM), a generator-produced positron-emitting 62Cu-labeled radiopharmaceutical, was studied with non-radioactive and radioactive copper. Changes in the chemical form of Cu-PTSM were detected by electron spin resonance spectrometry (ESR) with cold copper. The effects of electron transport chain inhibitors on the reduction of Cu-PTSM were also examined. Rotenone and antimycin A activated the reduction of Cu-PTSM in the brain mitochondria by 1.6- and 1.4-fold, respectively, compared with untreated controls, while thenoyltrifluoroacetone (TTFA) had no effect on the reduction. These results were confirmed with radioactive copper. Furthermore, this reduction of Cu-PTSM was dependent on the protein concentration of mouse brain submitochondrial particle (SMP) with 1 mM NADH (0 mg-protein/ml: 1.8 +/- 2.5%, 8 mg-protein/ml: 69.0 +/- 5.5%, each value was % of reduced Cu). Similarly, this reduction depended on NADH concentration at a fixed concentration of SMP (8 mg-protein/ml). These results indicated that the electron transport chain, especially complex I, participated in the reduction of Cu-PTSM in brain mitochondria, and this suggested that Cu-PTSM has the potential to act as a functional imaging agent for diagnosis of the electron transport chain.

Animals↗
PubMed2004

Chemical and radiological toxicity of depleted uranium.

A by-product of the uranium enrichment process, depleted uranium (DU) contains approximately 40% of the radioactivity of natural uranium yet retains all of its chemical properties. After its use in the 1991 Gulf War, public concern increased regarding its potential radiotoxicant properties. Whereas in vitro and rodent data have suggested the potential for uranium-induced carcinogenesis, human cohort studies assessing the health effects of natural and DU have failed to validate these findings. Heavy-metal nephrotoxicity has not been noted in either animal studies or Gulf War veteran cohort studies despite markedly elevated urinary uranium excretion. No significant residual environmental contamination has been found in geographical areas exposed to DU. As such, although continued surveillance of exposed cohorts and environments (particularly water sources) are recommended, current data would support the position that DU poses neither a radiological nor chemical threat.

Animals↗
PubMed2006

239+240Pu concentration and isotope ratio (240Pu/239Pu) in aerosols during high dust (Yellow Sand) period, Korea.

Concentration and isotope ratio of Pu were analyzed for aerosols collected at Anmyeondo located in the western coast of Korea using multiple collector inductively coupled plasma mass spectrometer equipped with desolvated micro-concentric nebulizer. Aerosols were collected from June 2001 to April 2002 using high volume air sampler. The samples consist of high dust samples (Yellow Sand), and also low dust samples; maximum Al concentration was 74.2 microg/m(3) and minimum was 0.17 microg/m(3). Pu was concentrated using 0.1 ml TEVA resin columns after conc. HNO(3) extraction. Isotope dilution using (242)Pu spike and mass bias correction using (233)U and (236)U mixed solution enabled the quantification of Pu and measurement of isotope ratio simultaneously. The contribution of (238)U from both spikes and samples was minimized by careful chemical separation and optimization of spike concentration. The (238)U(1)H and tail contribution on (239)Pu peak were about 0.75 x 10(-5) and 1 x 10(-5) of (238)U intensity, respectively, and they were corrected from (239)Pu using externally determined ((238)U(1)H + tailing)/(238)U ratio and (238)U measurement during acquisition. The detection limits of this analytical procedure were 0.61 fg/ml and 0.56 fg/ml for (239)Pu and (240)Pu, respectively (4 nBq/m(3) and 12 nBq/m(3) for (239)Pu and (240)Pu, respectively). The precision of isotope ratio measurement was better than 2% for larger quantity than 20 fg of (239)Pu. In spring, maximum concentration of 0.580 microBq/m(3) for (239)Pu and 0.404 microBq/m(3) for (240)Pu was observed when Al concentration was maximum, so called as Yellow Sand event. Pu concentrations in aerosols are well correlated with Al, a tracer of soil dust. The ratios of Pu/Al were 0.0082 (microBq/microg) and 0.0055 (microBq/microg) for (239)Pu/Al and (240)Pu/Al, respectively. Isotope ratios of Pu ((240)Pu/(239)Pu) in Yellow Sand samples show 0.191+/-0.014 close to those of global fallout. These facts indicate that Yellow Sand plays an important role in the behavior of Pu in the environment like other concomitant metals such as Al, Fe etc.

Aerosols↗
PubMed1998

Interactions between chitosan and alpha emitters: 238Pu and 241Am.

This paper deals with the first study published on the interactions between chitosan and two radioactive elements (alpha emitters): 238Pu and 241Am. The authors determined the optimal experimental conditions for each of them (pH, ionic strength (FI), carbonate concentration) and attempted to explain the mechanism of interaction. The study of the nature and the percentage of the metallic ionic species present in solution as a function of the experimental conditions was carried out by means of the TOT software for 241Am. The authors showed a good fixation of 238Pu and 241Am on chitosan for pH's between 11-12, with the best results for 241Am. Nevertheless, an increase of the FI or the addition of a complexant of these alpha emitters induced a decrease of the interactions with chitosan.

Alpha Particles↗
PubMedDate not supplied

[Distribution and activity of microorganisms in the deep repository for liquid radioactive waste at the Siberian Chemical Combine].

The physicochemical conditions, composition of microbial communities, and the rates of anaerobic processes in the deep sandy horizons used as a repository for liquid radioactive wastes (LRW) at the Siberian Chemical Combine (Seversk, Tomsk oblast), were studied. Formation waters from the observation wells drilled into the production horizons of the radioactive waste disposal site were found to be inhabited by microorganisms of different physiological groups, including aerobic organotrophs, anaerobic fermentative, denitrifying, sulfate-reducing, and methanogenic bacteria. The density of microbial population, as determined by cultural methods, was low and usually did not exceed 10(4) cells/ml. Enrichment cultures of microorganisms producing gases (hydrogen, methane, carbon dioxide, and hydrogen sulfide) and capable of participation in the precipitation of metal sulfides were obtained from the waters of production horizons. The contemporary processes of sulfate reduction and methanogenesis were assayed; the rates of these terminal processes of organic matter destruction were found to be low. The denitrifying bacteria from the underground repository were capable of reducing the nitrates contained in the wastes, provided sources of energy and biogenic elements were available. Biosorption of radionuclides by the biomass of aerobic bacteria isolated from groundwater was demonstrated. The results obtained give us insight into the functional structure of the microbial community inhabiting the waters of repository production horizons. This study indicates that the numbers and activity of microbial cells are low both inside and outside the zone of radioactive waste dispersion, in spite of the long period of waste discharge.

Bacteria↗
PubMed1996

Structural evidence for an anion-directing track in the hen ovotransferrin N-lobe: implications for transferrin synergistic anion binding.

The transferrins are a class of iron-binding proteins that require the presence of a synergistic anion for conformation-dependent binding of ferric ions. Bromopyruvate, a known synergistic anion and affinity label of ovotransferrin (oTF) [Bailey, C. T., Patch, M. G., & Carrano, C. J. (1988) Biochemistry 27, 6276-6282], was used to probe the structure of the metal- and anion-binding sites of the functional N- and C-terminal proteolytic halves (oTF/2N and oTF/2C, respectively) of ovotransferrin. Incubation of oTF/2N with [2-14C]bromopyruvate in the presence of Fe3+ ions resulted in the incorporation of 0.70 mol of 14C label/mol of oTF/2N; 14C-labeled oTF/2N was then purified and digested sequentially with trypsin and V8 protease to determine the sites of modification. Quantification of 14C radioactivity, analysis of purified 14C-labeled peptides by gas-phase sequencing and mass spectrometry demonstrated that chemical modification was restricted to nucleophilic residues contained in a fragment corresponding to residues 189-204 of oTF/2N, including Lys 199, Lys 202, and His 196. Lysine 199 was also protected from modification with [3H]CH2O in iron-saturated oTF/2N, suggesting the involvement of this residue in anion binding by the apo conformation [Anderson, B. F., Baker, H. M., Norris, G. E., Rumball, S. V., & Baker, E. N. (1990) Nature 344, 784-787]. Lysine 199 is conserved as a basic residue in the N-terminal metal-binding domains of the transferrins but not in the homologous C-terminal metal-binding domains. Identical trials with oTF/2C showed binding, but not modification, with bromopyruvate. These data suggest that Lys 199, Lys 202 and His 196, which are located on an alpha-helix (8) that terminates at the anion-binding site [Dewan, J. C., Mikame, B. Hirose, M., & Sacchettini (1993) Biochemistry 32, 11963-11968], attract and channel the synergistic anion to the anion-binding site. The presence or absence of basic residues in the metal-binding lobes of transferrins may account for the different anion- and metal-binding characteristics observed for the iron-binding sites of these proteins.

Amino Acid Sequence↗
PubMed1990

Nasal administration of a cognition enhancer provides improved bioavailability but not enhanced brain delivery.

Compound 1 [3,3-bis(4-pyridylmethyl)-1-phenylindolin-2-one] is an experimental cognition-enhancing drug now being developed for cognitive disorders. Oral bioavailability of 1 in rats was less than 10% of the dose. Nasal dosing improved bioavailability to greater than 50%. Brain levels of total radioactivity were measured after iv and nasal doses of radiolabeled 1. The ratio of AUCbrain:AUCplasma was the same by both routes, so nasal dosing did not enhance brain delivery. This is in contrast to other reports of large molecular weight substances and metals gaining direct access to the brain through the nasal epithelium.

Administration, Intranasal↗
PubMed2005

Effect of pH and aging time on the kinetic dissociation of 243Am(III) from humic acid-coated gamma-Al2O3: a chelating resin exchange study.

The chelating resin was studied to assess its influence on metal availability and mobility in the environment. The association of organic-inorganic colloid-borne trace elements was investigated in this work. The radionuclide 243Am(III) was chosen as the representative and chemical homologue for trivalent lanthanide and actinide ions present in radioactive nuclear waste. The kinetic dissociation behavior of 243Am(III) from humic acid-coated gamma-Al2O3 was studied at pH values of 4.0 +/- 0.1, 5.0 +/- 0.2, and 6.0 +/- 0.2 with a contact time of 2 days after the addition of a chelating cation exchanger resin. The concentrations of the components were: 243Am(III) 3.0 x 10(-7) mol/L, gamma-Al2O3 0.5 g/L, HA 10 mg/L (pH 4.0 +/- 0.1, 5.0 +/- 0.2, and 6.0 +/- 0.2) and 50 mg/L (pH 6.0 +/- 0.2), respectively. The kinetics of dissociation of 243Am(III) after different equilibration time with humic acid-coated gamma-Al2O3 was also investigated at pH 5.0 +/- 0.2. The experiments were carried out in air and at ambient temperature. The results suggest that the fraction of irreversible bonding of radionuclides to HA-coated Al2O3 increases with increasing pH and is independent of aging time. The assumption of two different 243Am(III)-HA-Al2O3 species, with "fast" and "slow" dissociation kinetics, is required to explain the experimental results. 243Am(III) species present on HA-Al2O3 colloids moves from the "fast" to the "slow" dissociating sites with the increase of aging time.

Actinoid Series Elements↗
PubMed1989

Initial permeability of the 19-day foetus to nickel.

The administration of 63NiCl2 to 19-day pregnant rats produced a limited transfer of nickel to the foetus. An experimental model based on the incubation of the conceptuses still connected to the maternal organism resulted in an appreciable net transfer of nickel through the amniotic membranes. The placenta retained a significant amount of radioactive nickel as did the lining of the uterine wall. The circulation of nickel through the foetus following the direction maternal blood----placenta----foetus----amniotic membranes----endometrium----maternal venous blood, is postulated. This transfer could provide an additional protection to placental barrier against metal toxicity.

Animals↗
PubMed2001

Bacterial diversity in soil samples from two uranium waste piles as determined by rep-APD, RISA and 16S rDNA retrieval.

The bacterial diversity in two uranium waste piles was studied. Total DNA was recovered from a large number of soil samples collected from different sites and depths in the piles using two procedures for direct lysis. Significant differences in the bacterial composition of the samples were revealed by the use of rep-APD, RISA and 16S ARDREA. The 16S rDNA analyses showed that the uranium wastes were dominated by Acidithiobacillusferrooxidans and by several Pseudomonas species classified in the gamma-subdivision of the Proteobacteria. The three kinds of A. ferrooxidans 16S and IGS rDNA specific fragments that were found corresponded to the three phylogenetic groups recognised in this species. This microdiversity probably reflects the genetic adaptation of the uranium waste strains to different concentrations of heavy metals.

Base Sequence↗
PubMed2002

Radioautographology general and special.

A new concept, termed "radioautographology" is advocated and its contents are reviewed. This term is the coinage synthesized from "radioautography" and "(o)logy", expressing a new science derived from radioautography. The concept of radioautographology (RAGology) is a science to localize the radioactive substances in the biological structure of the objects and to analyze and to study the significance of these substances in the biological structure. On the other hand, the old term radioautography (RAG) or autoradiography (ARG) is the technique to demonstrate the pattern of localization of various radiolabeled compounds in biological specimens. The specimens used in biology and medicine are cells and tissues. They are fixed, sectioned and made contact with the radioautographic emulsions, exposed and developed to produce metallic silver grains. Such specimens are designated as radioautographs (or autoradiographs) and the patterns of pictures made of silver grains are named radioautograms. Those people who produced radioautographs were formerly named radioautographers (or autoradiographers) who were only technicians, while those who study RAGology are not technicians but scientists and should be called as radioautographologists. The science of radioautographology was developed in the 20th century and can be divided into two parts, general radioautographology and special radioautographology, as most natural sciences usually can. The general radioautographology is the technology of RAG which consists of 3 fields of sciences, physics concerning radioactivity, histochemistry treating the cells and tissues and photochemistry dealing with the photographic emulsions. The special radioautographology, on the other hand, consists of applications of general radioautographology to various biological and medical sciences. The applications can be classified into several scientific fields, i.e., cellular molecular biology, anatomy, histology, embryology, pathology and pharmacology. Studies carried out in our laboratory were summarized and reviewed. The results obtained from the technology includes 4-dimensional structures of the organs taking the time dimension into account by labeling cells and localizing the sites of incorporation, synthesis, discharge of the labeled compounds in connection with the time lapse and aging of animals. All the results obtained from such applications should be systematized as a new filed of science in the future in the 21st century.

Animals↗
PubMed2004

Toxicity to Tradescantia of technogenic radionuclides and their mixture with heavy metals.

The genotoxic effects on Tradescantia of (137)Cs, (90)Sr, and (236, 242)Pu, a heavy metal mixture [Cd, Cr(VI), Cu, Mn(II), Ni, Pb, Zn] and of a complex mixture of these toxicants were determined. The impact of radionuclides on plants subjected to ionizing radiation exposure was estimated. The number of somatic mutations and the quantity of nonviable stamen hairs were used as end points in the testing. An increase in the quantity of nonviable stamen hairs was observed with increasing internal exposure to (137)Cs, (90)Sr, and (236, 242)Pu; however, the number of somatic mutations was not observed to be dependent on ionizing radiation. The internal dose of individual radionuclides necessary to decrease the quantity of viable stamen hairs in Tradescantia by 50% can be arranged in the following sequence: (236, 242)Pu > (137)Cs > (90)Sr. Tradescantia died in the mixture of the radionuclides (90)Sr, (137)Cs, and (236)Pu (5 x 10(-2), 7 x 10(-5), and 4 x 10(-10) Gy, respectively) after 14 days, whereas the heavy metal mixture caused somatic mutations in 3% of the Tradescantia and nonviable stamen hairs in 7% but no mortality. However, the Tradescantia died in a combined mixture of these heavy metals and the radionuclides after 14 days. On the basis of all these observations, it can be concluded that the toxic effect of radionuclides was more significant than that of heavy metals.

Cesium Radioisotopes↗
PubMed1989

[Biochemical states of zinc incorporated in the liver of mice treated with a radioelement after irradiation with a sublethal dose of gamma-rays].

Radioresistance has been observed in mice which have received an inorganic zinc 24 hours prior to gamma irradiation with a sublethal dose. In order to elucidate the mechanism of radioresistance, the biochemical states of the metal in filtrate extracted from the homogenated liver of the animal which have received an injection of zinc under the form of 65Zn as tracer 24 hours post irradiation, were analyzed and compared with those of non-irradiated (control) mice. Two peaks of radioactivity: P-1 and P-2, having molecular weight of about 45,000 and 20,000-25,000 respectively, were revealed by Sephadex G-75 separation. The radioactivity of P-2 (39%) from the irradiated mice is lower than that from the controls (46%). Chromatography of P-2 from control animals through DEAE-Sephadex A-50 revealed the existence of a large radioactive peak (P-U). Chromatography of P-2 from irradiated animals did not show any P-U peak. This P-U peak is composed principally from 2 to 3 proteins with a molecular weight of 12,000 to 26,000. Proteins of the P-U peak provoke a protection effect against the lethal effect of gamma-rays when they are injected into mice after irradiation.

Animals↗
PubMed1983

Influence of metal ions on the biosynthesis of N-acetylglucosaminyl polyprenols by the retina.

The following enzymatic process was investigated, catalyzed by an enzyme preparation from the retina of the embryonic chick: UDP-GlcNAc + dolichol phosphate GDPmannose leads to metal ions GlcNAc-P-P-polyprenol + (GlcNAc)2-P-P-polyprenol + Man-(GlcNAc)2-P-P-polyprenol. These reactions were carried out in the presence of a dolichol phosphate mannose-synthesizing system, shown previously to be an activator of GlcNAc-lipid synthesis. The process was also strongly influenced by the choice of the divalent cation used during the reactions. In the presence of Mg2+, not only was the extent of incorporation of radioactivity from UDP-[3H]GlcNAc increased 4-fold into the GlcNAc lipids, as compared to Mn2+, but the relative distribution of the products was affected as well. In the presence of Mg2+ the reaction was driven mainly in the direction of the formation of the first intermediate of the dolichol pathway, GlcNAc-P-P-polyprenol. Many of the other characteristics of the GlcNAc-transferases, such as pH optimum, requirement for dolichol phosphate and specificity for stimulation by sugar nucleotides, were similar for either the Mn2+ or Mg2+ systems. Retinol phosphate could not replace the requirement for dolichol phosphate. The influence of metal ions, in addition to the stimulation by dolichol phosphate mannose, on GlcNAc-lipid synthesis may be aspects of metabolic regulation of the dolichol pathway.

Animals↗
PubMed2006

Assessment of alternative management techniques of tank bottom petroleum sludge in Oman.

This paper investigated several options for environmentally acceptable management techniques of tank bottom oily sludge. In particular, we tested the applicability of managing the sludge by three options: (1) as a fuel supplement; (2) in solidification; (3) as a road material. Environmental testing included determination of heavy metals concentration; toxic organics concentration and radiological properties. The assessment of tank bottom sludge as a fuel supplement included various properties such as proximate analysis, ultimate analysis and energy content. Solidified sludge mixtures and road application sludge mixtures were subjected to leaching using the toxicity characteristic leaching procedure (TCLP). Tank bottom sludge was characterized as having higher concentrations of lead, zinc, and mercury, but lower concentrations of nickel, copper and chromium in comparison with values reported in the literature. Natural occurring radioactive minerals (NORM) activity values obtained on different sludge samples were very low or negligible compared to a NORM standard value of 100Bq/g. The fuel assessment results indicate that the heating values, the carbon content and the ash content of the sludge samples are comparable with bituminous coal, sewage sludge, meat and bone meal and petroleum coke/coal mixture, but lower than those in car tyres and petroleum coke. The nitrogen content is lower than those fuels mentioned above, while the sulfur content seems comparable with bituminous coal, petroleum coke and a petroleum coke/coal mixture. The apparent lack of leachability of metals from solidification and road material sludge applications suggests that toxic metals and organics introduced to these applications are not readily attacked by weak acid solutions and would not be expected to migrate or dissolved into the water. Thus, in-terms of trace metals and organics, the suggested sludge applications would not be considered hazardous as defined by the TCLP leaching procedure.

Conservation of Energy Resources↗