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Strontium-89 is an important radiotherapy nuclide in bone palliation. The standardization of 59Sr has been performed at the National Office of Measures (OMH) within the frame of the BIPM CCRI(II)-K2.Sr-89 key comparison. The activity concentration of the 89Sr solution was measured by two different methods. The conventional 4pi beta counting technique was used with two proportional counting measurement systems. The 4pi beta-gamma-coincidence efficiency tracing method was used with a 4pi beta-gamma-coincidence measurement system using 24Na as the tracer radionuclide. The beta efficiencies of each of these counting techniques were nearly 100%. The combined uncertainties of the activity concentration determined by these absolute methods are 0.3%. The general agreement of results between the two methods was 0.5%. The measurement equipment, evaluation methods and results of activity concentration measurements with their uncertainty budgets are reported.

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Pursuant to the Hungarian Law on Legal Metrology, activity measurements in nuclear medicine can be made by verified measuring instruments only. OMH has carried out this legal metrological task of verification for more than 15 years. This paper outlines the calibration results for 12 various radionuclides for more than fifty instruments in our program, experiences of the type approvals of about 10 radionuclide calibrator models and that of the practical usage, the results of the analysis of measurement errors and the human aspects of the measurements. In addition it reports on the bilateral cooperation in the past years between OMH (Hungary) and BEV (Austria) in the field of metrological supervision of radionuclide calibrators.

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INTRODUCTION: In vitro and in vivo studies were performed to elucidate the pathogenesis of amiodarone toxicity. METHODS AND RESULTS: Rats were treated with amiodarone alone (500 mg/kg body weight per day) or together with antioxidants (silibinin or MTDQ-DA: 50 mg/kg body weight per day) or with either antioxidant alone. They received amiodarone for 30 days and antioxidant for 33 days (3 days pretreatment). In vitro, amiodarone induced a dose-dependent chemiluminescence signal, which was inhibited by the two dihydroquinolin-type antioxidants (MTDQ-DA, CH 402). Chemiluminometric results from liver homogenate demonstrated that simultaneous treatment with silibinin partially prevented the liver homogenate superoxide anion radical scavenger capacity decreasing effect of amiodarone. Amiodarone treatment caused a significant increase of NADPH and Fe3+ induced lipid peroxidation in the liver microsomal fraction, which antioxidants (silibinin, MTDQ-DA) were unable to prevent. Light microscopy of the lung tissue in amiodarone-treated rats showed accumulation of foamy macrophages with thickening of the interalveolar septa, pneumonitis, and variable interstitial fibrosis. Antioxidant treatment did not prevent these changes. Electron micrographs of lung from amiodarone-treated rats showed lysosomal phospholipoidosis, intralysosomal electron dense deposits, and increased lysosome number and size. In contrast to rats treated with amiodarone alone, those treated with both amiodarone and silibinin had significantly fewer lysosomes (P < 0.01); the lysosome size, shape, and internal characteristics remained the same. Simultaneous treatment with silibinin and amiodarone decreased lysosomal phospholipoidosis compared to amiodarone treatment alone. Simultaneous treatment with MTDQ-DA and amiodarone did not show any beneficial effect. Pulse radiolysis and cobalt 60-gamma (60Co-gamma) radiolysis studies showed that the main free radical product in a reducing environment was a very reactive aryl radical formed after the partial deiodination of the amiodarone molecule. The radiosensitizing effect of amiodarone was also verified in rat liver microsomal preparations using in vivo amiodarone with or without MTDQ-DA pretreatment and 60Co-gamma irradiation with or without the in vitro addition of antioxidants (CH 402, MTDQ-DA). In vivo, the MTDQ-DA treatment also had a radiosensitizing effect; however, the in vitro addition of both antioxidants resulted in a radioprotective effect. The aryl radical also may emerge in vivo during the metabolism of amiodarone. CONCLUSION: These observations suggest that amiodarone in vitro and in vivo generates free radicals that may play a role in the pathogenesis of amiodarone toxicity beside other well-established mechanisms, and antioxidants may have a partial protective effect against amiodarone toxicity.

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It was supposed that free radicals are produced during the metabolism of amiodarone and involved in the mechanism of the drug's side effects. In vitro and in vivo experiments were performed in rats to check this hypothesis. We verified that amiodarone generated free radicals in vitro by chemiluminometric method. The light emission induced by amiodarone was inhibited by dihydroquinoline type antioxidants CH 402 and MTDQ--DA in a dose dependent manner. The malondialdehyde content, --one of the end products of lipid peroxidation--was increased by in vivo amiodarone administration in the serum and liver homogenate of rats. Amiodarone treatment increased significantly the NADPH and Fe3+ induced lipid peroxidation in rat liver microsomal fractions. The protective effect of antioxidants, MTDQ--DA and silibinin were ambiguous in these in vivo "short term" experiments.

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The non-toxic and water soluble dihydroquinoline type antioxidants: CH 402 (Na-2,2-dimethyl-1,2-dihydroquinoline-4-yl methane sulphonate) and MTDQ-DA (6,6-methylene bis 2,2-dimethyl-4-methane sulphonic acid: Na-1,2-dihydroquinoline) were studied in various in vitro tests in which oxygen free radicals were generated. Both compounds were shown to scavenge superoxide radical anions O2- produced in aqueous solution by pulse radiolysis with rate constants k (O2- + MTDQ-DA) = 4.10(8) dm3 mol-1 s-1 and k (O2- + CH 402) = 1.5.10(7) dm3 mol-1 s-1. CH 402 and MTDQ-DA reduced the H2O2 produced in the glucose-glucose oxidase reaction, which was detected by the luminol + hemin reaction with a chemiluminometric method. The dihydroquinoline type substrates inhibited the NADPH-induced and Fe3+ - stimulated lipid peroxidation and the ascorbic acid-induced non-enzymatic peroxidation pathways in microsomal fractions of rat and mouse liver.

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Groups of adult Wistar male and female rats were fed isoenergetically for a three and a six weeks period either with synthetic lipogenic diet containing 5% and 20% fat mixtures (in which sunflower oil and lard were blended according to the ratio of 35:65) or with the same synthetic diet containing the mixture of sunflower oil and interesterified lard in a similar ratio. A control group received a normal diet for 6 weeks, whereas one of the experimental groups (fed with the 20% fat mixture in the lipogenic diet for 6 weeks) was given the normal diet for an additional two weeks period. After the feeding periods had been completed serum HDL-C levels and the total lipid, triglyceride, total cholesterol, free fatty acid levels were determined in serum and liver. The distribution of fatty acids in liver and heart muscle was also evaluated. In comparison to the control values it has been found: 1. Consumption of the lipogenic diet which is known to increase the serum total lipid and total cholesterol content induced in male rats a smaller augmentation in these indices when consuming the 20% fat mixture with a P/S ratio approaching the ideal 1 values, than in case of a 5% fat mixture consumption. In case of female rats, considerable increases of the serum values, could be observed at both fat consumption levels. The serum triglyceride and HDL-C contents decreased for all experimental groups. 2. The total lipid and triglyceride content of the liver increased in a high degree, the fatty liver syndrome was developed--more rapidly in males than in females. The total lipid, triglyceride and total cholesterol contents of the liver of male rats exceeded those of females by 15-30%. 3. The interesterification of the lard component of fat mixture resulted in lipid indices similar to those without interesterification, or in certain cases, they were found to be even slightly more favourable, i.e. the biological effect of the technological change proved to be adequate. 4. After a two weeks regeneration period the serum values of the male rats approached closer the normal control values than those of the females which were decreasing from a very high level but the degree of decrease was greater for them than for the male rats. The lipid content of the liver showed similar values.(ABSTRACT TRUNCATED AT 400 WORDS)

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In blood samples of 54 obese persons (13 men, 41 women) some lipid components, malondialdehyde (MDA), and the activities of free radical protecting enzymes superoxide-dismutase (SOD) and glutathione-peroxidase (GSHpx), were determined before and after a seven-day slimming diet of 2.1 MJ/day. Body weight, triglycerides, HDL-cholesterol, and HDL-3-cholesterol all decreased, total cholesterol increased after the seven days hospitalization. After continuing the slimming diet (5.0-6.3 MJ/day) at home, HDL-2-cholesterol increased and total cholesterol returned to the initial value after three months. MDA decreased in the groups of hyperlipoproteinemia II/a and II/b and also in the group with high cholesterol and triglyceride levels (above 5.7 and 2.7 mmol/l). Correlation coefficients refer to the dominant role of high TG in the intensity of lipid peroxidation. The activity of SOD fell after the slimming, independent of lipid parameters. GSHpx activity remained unchanged except a drop in the male participants having high cholesterol levels. The behavior of the free radical protecting enzymes needs further examination.

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Adult male and female Wistar rats were fed isoenergetically for a 6 week period with a lipogenic diet containing a 20% fat mixture which caused fat-metabolism disturbance. One group consumed the mixture of sunflower oil and lard in a ratio of 0.91 P/S, the other group the interesterified form of the same mixture. The linoleic acid content of the mixtures was 0.4%. The fat mixture of the third group's diet was adjusted with soya oil to a linoleic-acid content of 0.8%. The results were compared to the control data obtained in rats fed with a normal diet. The changes in various lipid indices of the serum and the liver and the levels of some metals in the liver were analysed. It was found that; in comparison to the control on the effect of the lipogenic diet the total lipid and cholesterol contents of the serum increased significantly in all groups (a significantly higher value being observed for the females than for the males) whereas the HDL-C content decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

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In the blood sera of 70 obese persons (26 men, 44 women) some lipid components and malondialdehyde (MDA) level were determined before slimming. The people were classified into groups of hyperlipoproteinaemia on the basis of laboratory results, according to Fredrickson and Lees. In 32 people with high blood cholesterol level (above 5.7 mmol) there were negative correlations between MDA and high-density lipoprotein (HDL) fractions. Correlation coefficients were the greatest in the group IIa of hyperlipoproteinaemia (HDL-C. r = -0.74; HDL-2-C. r = -0.54; HDL-3-C. r = -0.78). Correlations were not found in subjects with a normal cholesterol level. The results were attributed to the formation of oxidized cholesterol products, caused by lipid peroxidation, which may decrease the HDL synthesis. It seems that in hypercholesterolaemia coupled with obesity, lipid peroxidation can contribute to the reduction in HDL levels, which is an important protective factor against cardiovascular diseases.

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The exocrine function of the pancreas was investigated in the course of adaptation to regular physical activity. In albino rats exercized by swimming for six weeks it has been observed that - in response to an identical physiological stimulation (liquid food via gastric tube) and under ad libitum feeding the rate of secretion and enzyme activity exceeded control values by 100 to 150%; - in pair-fed rats the values of the exercized animals were 50 to 70% higher, and - vagotomy suspended this effect even when food was offered ad libitum. On the basis of these results adaptation to regular exercise involves the exocrine function of the pancreas. In this functional increase both the increased food intake after training sessions and the direct effect of muscular work have a share. For adaptation an intact innervation is necessary.

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