Haematological studies on90Sr-90Y-toxicity

Summary Erythropoietic changes were observed, measured by⁵⁹Fe-uptake into red blood cells, and on radioiron turnover from blood plasma, at different time intervals (2–64 days) after treating adult female mice with varying activities of⁹⁰Sr-⁹⁰Y. Activities of 2.5 or 5.0 µCi radiostrontium per animal lead to a depression at time intervals of two and four days, at longer periods there was an overshoot. With activities of 0.5 or 1.0 µCi radiostrontium disturbances in the radioiron uptake are still observed, although these effects are not as pronounced as in experiments with higher burdens. In comparison with results obtained in experiments in which the plasma⁵⁹Fe-turnover was applied, even with an activity of 5 µCi radiostrontium per mouse, no deviation as against the untreated controls was detected.Dedicated to Prof. Dr. Hermann Muth, Homburg/Saar, on the occasion of his 65th birthday     

Transfer of 85Sr and 134Cs from diet to reindeer foetuses and milk

Sr-85 and ¹³⁴Cs in aqueous solution of the chlorides were administered daily to four pregnant reindeer during the last part of gestation. Radionuclide concentrations were determined in calves sacrificed at birth, and secretion of the nuclides was measured in milk. Although the gastrointestinal absorption of ⁸⁵Sr was low, an apparently higher transfer of the absorbed fraction of ⁸⁵Sr than ¹³⁴Cs from the mother to the foetus led to similar accumulation of ⁸⁵Sr and ¹³⁴Cs in foetuses. At birth 1.4–1.6 and 1.5–2.5% of the total administered activities of ⁸⁵Sr and ¹³⁴Cs, respectively, were present in the calves‘ bodies. Transfer coefficients (F _m) for ⁸⁵Sr and ¹³⁴Cs from feed to milk were estimated at 0.0218±0.0026 and 0.185±0.025 day kg⁻¹, respectively, and the observed ratio (OR_milk-diet) for ⁸⁵Sr was 0.124±0.037. Transfer of radiostrontium to reindeer milk was in agreement with previously reported relationships between Ca intake and radiostrontium transfer in ruminants. These relationships suggest that the transfer of radiostrontium to foetuses and milk of free-ranging reindeer can be 3–4 times higher than observed in this experiment (due to lower Ca intake with natural forage), but the transfer to milk will not be as high as that of ionic ¹³⁴Cs. The concentrations of ⁸⁵Sr in milk suggested that the does mobilized skeletal stores of Ca and ⁸⁵Sr for milk production, although the diet appeared to satisfy the Ca requirements. In reindeer with radiostrontium intake during the whole year, radiostrontium concentrations in milk will therefore be higher than indicated by the F _m value observed in our study. No differences in half-times for ⁸⁵Sr and ¹³⁴Cs secretion in milk were detected. Both nuclides were secreted with short- and long-term half-times of 1–2 and 12–19 days, respectively. For ⁸⁵Sr, 80–90% of the activity was excreted with the short half-time, whereas the corresponding value for ¹³⁴Cs was 30–50%.     

Dependence of radiostrontium uptake by pea and lupin on the content of calcium in the nutrient solution

In lupin (Lupinus albus L.) and pea (Pisum sativum L., cv. Raman) it was shown that the uptake of⁸⁹Sr from Knop's nutrient solution is significantly increased from a solution with decreased calcium content (one tenth of the normal content) and is slightly decreased from a solution with higher calcium content (150% of the normal content). The calciphile pea absorbs approximately 50% more calcium than the calciphobe lupin, and accordingly 50% radiostrontium less. The pea plant more strongly blocks the translocation of radiostrontium from roots to overground parts, as is proved by the higher discrimination factor of pea (i.e. by the ratio of specific activities of mCi⁸⁹ Sr/g Ca of roots to overground parts). The presence of chlorine in the nutrient solution decreases the content of radiostrontium per gram of dry matter, both in pea and lupin. Radiostrontium is absorbed quickly by both species of plants and is autoradiographically detectable as early as 2 hours after the introduction of radiostrontium to the nutrient solution. *** DIRECT SUPPORT *** A01GP049 00004     

Stronium Mobility in Germinating Seeds and Plants

The uptake of strontium in the bean plant (Phaseolus vulgaris) was linear for the first 34 hr during continuous exposure to radiostrontium. After 35 hr there was a sharp increase in the rate of uptake to 48 hr. Radioactivity could be detected in the plant as early as 1 hr after addition of radiostrontium to the growth medium.     

Removal of radioactive strontium from the rat by feeding stable strontium

The effect of administering the stable isotope of strontium (as phos-phate) at different dietary levels to adult rats (fed on a cereal and pulse-based diet containing 0.4% Ca) on the retention of radiostrontium (⁸⁹Sr) and radiocalcium (⁴⁵Ca) in the femur and the whole skeleton was studied for a period up to 6 weeks after an intraperitoneal injection of the two radioisotopes. The ability of strontium to remove⁸⁹Sr under the above dietary conditions was examined. Feeding Sr at 0.5% or 1% levels for 6 weeks had no effect on the skeletal content of⁸⁹Sr or⁴⁵Ca while a dietary regimen of 2% Sr (2000 times the normal content), significantly lowered the⁸⁹Sr and⁴⁵Ca content by about 30% in the femur but not in the whole skeleton. At this Sr level, the urinary excretion of the isotopes increased with a concomitant decrease in their excretion in the faeces. This study underscores the limitations of dietary Sr to mobilise⁸⁹Sr from the bones after it is incorporated in the bone mineral.     

Radiostrontium contamination of soil and vegetation within the Semipalatinsk test site

The Semipalatinsk nuclear test site (STS) in the Republic of Kazakhstan was an important site for testing atomic bombs and other civil and military nuclear devices of the former Soviet Union. Results are presented from investigations on the extent of radiostrontium contamination in soils and vegetation at the technical areas of the STS, where the tests were conducted and in pastures used by farmers for grazing animals or for hay production. Our data are compared with those reported largely in the recent Russian language literature that has been reviewed. The extent of ⁹⁰Sr contamination of soil is highly variable over the STS with the highest values associated with the technical areas, particularly the Degelen mountains. Recently measured values in both the present data and the Russian language literature confirm the relatively high current contamination of soil and vegetation in the vicinity of tunnels and associated watercourses in the Degelen area. The proportion of ⁹⁰Sr in soil which could not be extracted with 6 M HCl was only an average of 20%, which is low compared to other test site areas and possibly indicates a relatively high mobility in this area, because the ⁹⁰Sr is derived from leakage from explosion tunnels along watercourses rather than being associated with fused silicates. A comparison of relative activity concentrations in soil and vegetation suggests that the transfer of ⁹⁰Sr to vegetation on the STS is high compared to that of ¹³⁷Cs and plutonium.     

Studies of Inhibition of Intestinal Absorption of Radioactive Strontium: IV. Estimation of the Suppressant Effect of Sodium Alginate

A method is reported which permits selective suppression of absorption of radioactive strontium from ingested food material, allowing calcium to be available to the body. Studies were carried out on the inhibitory effect of various amounts of sodium alginate and the dose-response relationship of Sr⁸⁹ and bone uptake. The results obtained indicated that under laboratory conditions sodium alginate effectively reduces Sr⁸⁹ uptake in a constant proportion. This effect was observed at the three levels of administration of 1.4%, 12% and 24% of sodium alginate. The linear relationship between the dosage of the radioisotope and the bone uptake in the presence of sodium alginate suggests that the same proportion is maintained at the lower levels of intake of radioactive strontium.Previous studies with small constant doses of sodium alginate were extended in rats to a period corresponding approximately to three years of human life span. Low doses were sufficient to reduce appreciably bone uptake of radiostrontium.     

Studies on Inhibition of Intestinal Absorption of Radioactive Strontium: I. Prevention of Absorption from Ligated Intestinal Segments

A method is reported which permits selective suppression of absorption of radioactive strontium from ingested food material, permitting the calcium to be available to the body. Studies were carried out in vivo by injection of Sr⁸⁹ and Ca⁴⁵ in the presence of inert carrier into ligated intestinal segments in rats, and the amount of absorption was measured by standard monitoring techniques. The pattern of absorption of both ions is very similar but the rate of absorption is different. It was found that the polyelectrolyte, sodium alginate, obtained from brown algae (Phaeophyceae), injected simultaneously with radiostrontium effectively reduces the absortion of Sr⁸⁹ from all segments of the intestine by as much as 50-80% of the control values. No significant reduction in absorption of Ca⁴⁵ was observed in equivalent concentrations. The reduction in blood levels of Sr⁸⁹ and in bone uptake corresponded to the absorption pattern. The difference in the effect on strontium and calcium absorption may be due to differences in the binding capacity of sodium alginate from the two metal ions under the conditions present in vivo.     

The use of dietary calcium intake of dairy ruminants to predict the transfer coefficient of radiostrontium to milk

Transfer coefficients (the equilibrium ratio be-tween radionuclide activity concentration in milk or meat and the daily intake of radionuclide) are widely used to predict the contamination of animal products following the release of radionuclides into the environment. For a transfer coefficient to be generally applicable, its value must be constant for a range of circumstances. However, this is not the case for radiostrontium, the behaviour of which is strongly influenced by that of the homeostatically controlled nutrient, calcium. In this study, a relationship is derived between radiostrontium transfer coefficients and dietary calcium intake which takes into account the observed ratio for strontium:calcium transfer to milk. This relationship is tested against a range of observed data collated from the literature (n = 30) and found to account for 93% of the variability in transfer coefficient values. Model calculations show that a reduction in F _m of at least 40%–60% would be expected if dairy cattle, fed rations typical for well-managed herds, were supplemented with 100–200 g per day. Larger reductions would be predicted when dietary calcium intake is low. Received: 14 October 1996 / Accepted in revised form: 26 November 1996     

<Superscript>137</Superscript>Cs, <Superscript>40</Superscript>K, <Superscript>238</Superscript>Pu, <Superscript>239+240</Superscript>Pu and <Superscript>90</Superscript>Sr in biological samples from King George Island (Southern Shetlands) in Antarctica

There are few data reported on radionuclide contamination in Antarctica. The aim of this paper is to report ¹³⁷Cs, ⁹⁰Sr and ^238,239+240Pu and ⁴⁰K activity concentrations measured in biological samples collected from King George Island (Southern Shetlands, Antarctica), mostly during 2001–2002. The samples included: bones, eggshells and feathers of penguin Pygoscelis papua, bones and feathers of petrel Daption capense, bones and fur of seal Mirounga leonina, algae Himantothallus grandifolius, Desmarestia anceps and Cystosphaera jacquinotii, fish Notothenia corriceps, sea invertebrates Amphipoda, shells of limpet Nacella concina, lichen Usnea aurantiaco-atra, vascular plants Deschampsia antarctica and Colobanthus quitensis, fungi Omphalina pyxidata, moss Sanionia uncinata and soil. The results show a large variation in some activity concentrations. Samples from the marine environment had lower contamination levels than those from terrestrial ecosystems. The highest activity concentrations for all radionuclides were found in lichen and, to a lesser extent, in mosses, probably because lichens take up atmospheric pollutants and retain them. The only significant correlation (except for that expected between ²³⁸Pu and ^239+240Pu) was noted for moss and lichen samples between plutonium and ⁹⁰Sr. A tendency to a slow decrease with time seems to be occurring. Analyses of the activity ratios show varying fractionation between various radionuclides in different organisms. Algae were relatively more highly contaminated with plutonium and radiostrontium, and depleted with radiocesium. Feathers had the lowest plutonium concentrations. Radiostrontium and, to a lesser extent, Pu accumulated in bones. The present low intensity of fallout in Antarctic has a lower ²³⁸Pu/^239+240Pu activity ratio than that expected for global fallout.     

Lysosomal Fragility induced by Prostaglandin F2α

PROSTAGLANDINS have been suggested as mediators of inflammatory reactions because they increase vascular permeability^1,2, are found in inflammatory exudates³, are released during antigen-antibody reactions⁴ and have leucotactic properties⁵. For this reason and because lysosomes have been assigned an important role in the pathogenesis of diverse tissue injury reactions⁶, we have studied the effect of prostaglandins on lysosomal fragility.     

Synthesis,Physicochemical Properties,and in vitro Antibacterial Screening of Palladium(II) Complexes Derived from Thiosemicarbazone

A new series of Pd^II complexes derived from thiosemicarbazone has been synthesized. The synthesized Pd^II complexes have been characterized on the basis of elemental analyses, FT‐IR, ¹H‐ and ¹³C‐NMR, UV/VIS, and thermal studies. A square‐planar geometry has been assigned around Pd^II ions on the basis of results obtained from UV/VIS studies. The thiosemicarbazone ligand and its Pd^II complexes have been screened against Gram‐positive (Bacillus subtilis and Staphylococcus aureus) and Gram‐negative (Escherichia coli and Pseudomonas aeruginosa) bacteria in vitro as growth‐inhibiting agents, and the results revealed significant antibacterial activities.     

Blockers of Ca2+ channels in the plasmalemma of perfused Characeae cells

Ionic currents in the plasmalemma of perfused Nitella syncarpa cells identified as currents through Ca²⁺ channels were registered for the first time. The effect of 1,4-dihydropyridine derivatives (nifedipine, nitredipine, riodipine) and phenylalkylamines (verapamil, D600) as well as the agonist CGP-28392 on the Ca²⁺ channels in the plasmelemma of perfused cells of Nitellopsis obtusa and Nitella syncarpa have been studied. A blocking effect of 1,4-dihydropyridine derivatives and phenylalkylamines on the plasmalemma Ca²⁺ channels has been detected. Phenylalkylamines have been found to block both inward and outward Ca²⁺ currents. The activating effect of the agonist CGP-28392 on the Ca²⁺ channels of plasmalemma has been shown.     

Induction-resonance energy transfer between the terbium-binding peptide and the red fluorescent proteins DsRed2 and TagRFP

Two novel FRET-pairs: Tb³⁺-binding peptide-DsRed2 and Tb³⁺-binding peptide-TagRFP have been produced based on the terbium-binding peptide and the red fluorescent proteins DsRed2 and TagRFP. Two induction-resonance energy transfer processes in both FRET-pairs have been registered, from tryptophan of the terbium-binding peptide to Tb³⁺ and from sensitized Tb³⁺ to the acceptor, the chromophore, DsRed2 or TagRFP. The lifetimes of terbium in the presence and absence of the acceptor have been determined. It has been shown that the lifetime of Tb³⁺ in the presence of 150 mM NaCl decreases in both FRET-pairs. The efficiency of fluorescent resonance transfer from Tb³⁺ to the acceptor proteins is 28 and 35% for Tb³⁺-binding peptide-DsRed2 and Tb³⁺-binding peptide-TagRFP, respectively.     

Microwave Assisted Alcoholysis of Isocyanates Derived from N<Superscript>α</Superscript>-[(9-fluorenylmethyl)oxy]carbonyl Amino Acids: Synthesis of N-Fmoc-N<Superscript>1</Superscript>-Z-/Boc-/Alloc-/Bsmoc-gem-diamines

A general and efficient method has been developed for the alcoholysis of isocyanates derived from the N^α-[(9-fluorenylmethyl)oxy]carbonyl amino acids with various alcohols including hindered ones assisted by MW irradiation. Thus, the synthesis of N, N¹-diurethane protected gem-diamines wherein Fmoc protection on one of the amino groups and Z-/Boc-/Alloc or Bsmoc group on the other amino function has been accomplished. All the new orthogonally diurethane protected gem-diamines have been obtained as crystalline solid powders in 80 to 94% yield. The bisprotected gem-diamines have been fully characterized by IR, ¹H NMR, ¹³C NMR as well as by mass spectrometry.     

Galactosyltransferase activities in subcellular fractions of two YC8 lymphoma cell variants: does a relationship exist between antigenic determinants and acceptor sites for galactose?

Experiments have been undertaken to correlate physiological changes, observed in two YC8 cells variants (P and L) and some of their immunological and enzymatic properties. These cell lines show different responses towards antilymphocyte and anti-Moloney sera. Subcellular fractionations have been made. The A fractions (d: 1.14/1.16) have the highest ouabain-inhibited Mg²⁺-stimulated (Na⁺-K⁺)-dependent ATPase and galactosyltransferase activities. Some properties of the latter enzyme have been studied: whereas optima pH and requirements for Mn²⁺ ions have been found to be the same for both cell line enzymes, on the contrary, different kinetic parameters have been shown with respect to sugar donor (UDP-galactose) on endogeneous or exogeneous (ovomucoid) acceptors. Apparent Km for UDP-galactose is 1.7 × 10⁻⁶ M (P-cells) and 3.3 × 10⁻⁶ M (L-cells), on endogeneous acceptors, and P-cell V max < L-cell V max; on ovomucoid it is 0.61 × 10⁻⁶ M, for both cell lines. These results suggest the presence on L-cells of more endogeneous acceptor sites, the higher affinity of P-cells for UDP-galactose being balanced by less endogeneous acceptor sites for galactose. When ovomucoid is added, galactose transfer on endogeneous acceptor sites of both cells is negligible. Apparent Km for ovomucoid is 8.6 × 10⁻⁵ M (P-cells) and 4.3 × 10⁻⁵ M (L-cells). These data support the above-mentioned hypothesis: L-cell enzymes would be more rapidly saturated than P-cell enzymes because of the higher number of endogeneous sites on L-cells.This supposed acquired character of L-cells as well as their immunological behaviour could explain the modified properties of L-cells as compared to P-cells.     

Hydrogen-deuterium exchange of the tryptophan residues in bovine α-lactalbumin

Effects of deuteration on the Raman spectrum of a tryptophan residue have been examined. The 1386 cm^?1 line of deuterated tryptophan residue has been found to be useful for tracing the hydrogen-deuterium exchange reaction of this residue in a protein. An examination on bovine α-lactalbumin at pH 6.4 and at 20°C indicates that two of the four tryptophan residues exchange with a rate constant much greater than 9 × 10^?4 sec^?1, while the other two exchange with a rate constant of 4 × 10^?5 sec^?1. The latter two have been assigned to Trp 28 and Trp 108 of this protein. The kinetics of hydrogen-deuterium exchange reaction of completely “free” tryptophan residue have been examined by a proton magnetic resonance study on tryptophan itself. By taking the result of this examination into account, the chance of exposure to the solvent for Trp 28 or Trp 108 has been estimated to be 3 × 10^?6 at pH 6.4 and at 20°C.     

Carbon-13 nuclear magnetic resonance spectra of carbohydrate oxirane derivatives

The ¹³C-chemical shifts and ¹J_C,H values of two series of carbohydrate oxirane derivatives, namely methyl 2,3-anhydro-ribo- and -lyxofuranosides and methyl 2,3-anhydro-4,6-O-benzylidene-manno- and -allopyranosides have been determined. The assignment of ¹³C resonances has been established mainly by the examination of the proton-coupled and the selective proton-decoupled spectra. The effect of the oxirane rings on the chemical shifts of β and γ carbon atoms (from the oxirane ring oxygen atom) has been observed. Large ¹J_C,H values associated with cis CH bonds adjacent to the oxirane rings relative to those of trans counterparts have been found.     

In vitro: Régénération de plants de fraisier à partir de fragments de pétioles et de bourgeons floraux

Strawberry plants have been regenerated from petioles and flower buds Petiole segments derived from strawberry plants(Fragaria vesca L. andFragaria xananassa Duch. cvs. Gorella and Redgauntlet) maintainedin vitro have been cultured on the Gambobg’s. agar medium supplemented with 2,4-D (2 mg 1?¹) either alone or with kinetin or BAP (0.1 mg I?¹ or 1 mg I?¹). The calli thus obtained have been transferred to media differing from the first ones only by the nature and the concentration of the growth regulators used. One or two months later, shoots appeared on these calli. The influence of the media hormonal content on plant regeneration has been observed. Moreover, genotypic variations have also been investigated: the wild strawberry exhibited the greatest organogenic capacity. Shoots have also been obtained from flower buds(Fragaria xananassa Duch. cvs. Fern, Hummi Gento, Gorella and Redgauntlet). In this case, shoots appeared directly on small calli derived from the peduncular base of the flower buds. These regenerations have been observed, without changes of media, on the Lee and de Fossabd’s agar medium.     

The Conformational Analysis of Serine Protease Inhibitors and Its Applications for Drug Design

Abstract

Introduction

In our laboratory we have focused on several enzymes, among them β-glucuronidase, which have been shown to be released in abnormal quantities during chronic inflammatory diseases such as Rheumatoid Arthritis.^1,2 This enzyme, which is involved in the catalysis of β-glucuronides, has been characterized in mammalian tissues.³ In previous studies^4,5 we have demonstrated that it was inhibitied by a number of synthetic antiinflammatory gold (I) complexes, such as gold (I) thiomalate (Myochrisin) and gold (I) thiosulfate (Solganol). although the mechanism of inhibition has not been verified we have suggested from these and previous studies⁶ that a thiol group on the enzyme may be the primary site of binding to the gold complex.