[Quality control of radiopharmaceuticals (II): evaluation of radioactive impurities in radiopharmaceuticals (author's transl)].
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Biomedical subjects
Publications and source records attributed to R Amano.
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A simple, systematic analytical method for multiple mycotoxins was developed for detecting 14 mycotoxins; aflatoxins B1, B2, G1, and G2, sterigmatocystin, T-2 toxin, diacetoxyscirpenol, neosolaniol, fusarenon X, zearalenone, ochratoxin A, citrinin, luteoskyrin, and rugulosin. These mycotoxins were extracted with 20% H2SO4-4% KCl-acetonitrile (2 + 20 + 178), defatted with isooctane, and transferred to chloroform. The chloroform extract was cleaned up by silica gel column chromatography; the first 10 toxins were eluted with chloroform-methanol (97 + 3) and the remaining 4 toxins with benzene-acetone-acetic acid (75 + 20 + 5). Each fraction was analyzed by thin layer chromatography for the final determination. The method has been applied to polished rice, rough rice, corn, wheat, and peanuts as an analytical screening procedure. The detection limits in these commodities ranged from 10.00 to 800.0 microgram/kg, depending on the mycotoxin, but all limits were superior to those obtained for the individual mycotoxins by using other methods.
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For the purpose of calculating absorbed dose to humans from 167Tm-citrate, the whole-body retention studies using 5 rats were carried out. Up to 40 days following intravenous injection of 167Tm-citrate, the whole-body counts were monitored with a animal counter. The whole-body retention curve was obtained with three exponentaial components. Namely, the 26% of the injected 167 Tm-citrate had a biological half-time of 3.4 hours, 12.5% had a biological half-time of 99 hours and 61.5% had a biological half-time of 106 days. These results indicate, that three components consist of the rapid clearance from the kidneys, the retention in the liver and other soft tissues with relatively long half-time and the retention in the bones with long half-time. Based on these biological data and the MIRD Committee method, the average dose estimates to the bone and whole-body from intravenous administration of 1 mCi 167Tm-citrate were 7.08 rads and 1.28 rads, respectively.
Porcine thymus lactosylceramide beta-galactosidase was purified by a simple procedure. In the final step of isoelectric focusing the enzyme was separated into two peaks of pI 6.3 (peak I) and 7.0 (peak II), which showed 3,600- and 4,000-fold enhancement of lactosylceramide-hydrolysing activity, respectively. The two peaks had identical mobility on polyacrylamide gel electrophoresis. The apparent molecular weight was 34,000. Neither monosialoganglioside (GM1) nor galactosylceramide was hydrolysed by the purified enzyme fractions. The optimal pH was at 4.6, and sodium taurocholate was essential for the reaction. The apparent Km was 2.3 x 10-5 M. The reaction was stimulated by sodium chloride and linoleic acid, while it was strongly inhibited by Triton X-100 and bovine serum albumin. Galactosylceramide, p-nitrophenyl beta-galactoside, and p-nitrophenol were weak inhibitors. No effects of GM1 and galactose were observed on the hydrolysis of lactosylceramide.
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Forty-six children with refractory epilepsy (12 with symptomatic generalized epilepsy, 14 with symptomatic partial epilepsy, and 20 with undetermined epilepsy) were treated by high-dose (serum level above 100 micrograms/ml) valproate (VPA) therapy. Monotherapy was used with 34 patients and two drugs with 12. Serum VPA concentrations ranged from 105.1 to 198.4 micrograms/ml. Assessment of initial response to treatment, after the serum level had reached the appropriate level, showed seizures to be completely controlled in 15 (32.6%) of 46 patients and improved in 12 (26.1%) (50% or more). Follow-up of more than 6 months after the time of initial response showed control of seizures in 14 (30.4%) and improvement in 11 (23.9%). The initial effect on EEG was the disappearance of epileptic discharges in 3 (6.5%) of 46 patients and marked improvement in 15 (32.6%). Follow-up revealed the disappearance of epileptic discharges in 7 (15.2%) and marked improvement in 9 patients (19.6%). High-dose VPA therapy was especially effective for West syndrome and for epilepsy with continuous spike-waves during slow-wave sleep. Control of atypical absences and myoclonic seizures was relatively good. Hypofibrinogenemia and thrombocytopenia were sometimes encountered but these side effects were reversible with reduction of dosage.
The radioactive multitracer technique was applied to simultaneous evaluation of biobehavior of many trace elements in normal, Al-overloaded and Cd-overloaded mice. The tissue and subcellular distributions of Be, Sc, V, Mn, Fe, Co, Zn, As, Se, Rb, Sr, Y, Zr, Ru, and Rh were examined by using a multitracer solution, prepared from an Ag target irradiated with heavy ions, in 9 organs (brain, cardiac muscle, lung, liver, spleen, pancreas, kidney, skeletal muscle, and bone) and blood. Their tissue and subcellular distributions were evaluated by gamma-ray spectrometry in terms of tissue uptake rate (the radioactivity percentage of injected dose per gram of tissue, percent of dose/g) and fractionation percentage (the radioactivity percentage of nuclear fraction, mitochondrial fraction, microsomal fraction or supernatant fraction, percent), respectively. Comparative biobehavior of these elements in brain and liver is reported. Aluminium- and Cd-induced synergistic interactions were observed among these trace elements in their liver uptake behavior.
Relative tissue distributions of Sc, Mn, Fe, Co, Zn, Se, Rb, Y, and Zr tracers were studied in young mice housed under four different O2 atmospheres (10 percent, 20 percent, 80 percent, and 100 percent O2) using the radioactive multitracer technique developed at The Institute of Physical and Chemical Research (RIKEN). At 48 hr after injection of the multitracer, the tissue uptake rates were examined for 10 tissues (brain, cardiac muscle, lung, liver, spleen, pancreas, kidneys, skeletal muscle, bone, and blood) and expressed as the radioactivity percentage of the injected dose per gram of wet tissue (percent dose/g). Rubidium uptake rates for all soft tissues of mice housed under a 10 percent O2 atmosphere were found to be higher than those of the tissues of mice housed under the other three O2 atmospheres (20 percent, 80 percent, and 100 percent), but no difference was observed for the other elements (Sc, Mn, Fe, Co, Se, etc.) under any of the O2 atmospheres.