Contribution to the penetration of radionuclides across the skin. Concentration dependence of strontium through the skin in vitro.

Toxicological studies of radionuclide passage across the skin, which represents a crucial barrier of radiation, are important for ensuring the quality of the environment. Both (137)Cs and (90)Sr are most frequently involved in radionuclide contamination of the human body. In our study, we selected (90)Sr because this radionuclide is chemically very close to the bio-element calcium. The permeation of (90)Sr from donor solution across the intact skin of 5- or 9-day-old rats (5DR, 9DR) and across stripped and split skin of the 5DR was studied. The experiments in vitro were carried out using vertical diffusion cells. Strontium chloride (SrCl(2)) was used as carrier in the donor solution in different concentrations. Liquid scintillation spectrometry was applied for radiation detection. The experiments showed that: the permeated fraction of (90)Sr(2+) was indirectly proportional to the carrier concentration in the donor solution; the stratum corneum was found to be the principal penetration barrier of strontium; and in the case of the 9DR the dominant route of strontium penetration was along the follicles.

Pharmacokinetic study of stobadine.

The aim of this paper is to provide a brief overview of most important results of stobadine kinetic studies in rats, dogs, and human volunteers. In these studies, stobadine dihydrochloride and stobadine dipalmitate was used for intravenous and oral administration, respectively. To evaluate kinetic properties of stobadine and its metabolites, TLC, HPLC, GLC, GC-MS, radiometric, and fluorometric methods were developed and used.

Endothelin-1 significantly increased number of specific high-affinity 1,4-dihydropyridine (DHP) binding sites photolabelled on vascular smooth muscle cells with (-)-[3H]-azidopine.

The effects of endothelin-1 (ET-1) on surface membrane Ca2+ channels were studied on cultured human embryonal vascular smooth muscle cells (VSMC) and on isolated rat aorta using photoaffinity labelling with DHP Ca2+ channel antagonist (-)-[3H]-azidopine (AZI). The AZI-labelled saturable population of sites on VSMC with Bmax = 1.59 +/- 0.10 pmol/mg of protein and KD = 5.40 +/- 1.70 nmol/l; and 1.32 +/- 0.11 pmol/mg w.w. and KD = 1.09 +/- 0.20 nmol/l in isolated rings of the rat aorta. Preincubation with ET-1 (0.1, 1.0 and 10 nmol/l) increased (in a concentration-dependent manner) the total number of sites specifically photolabelled on VSMC. The number of sites labelled with AZI on ET-1 preincubated VSMC increased markedly when divalent cations (Ca2+ or Mg2+ in other experiments) were present in the incubation medium. Specific photolabelling also significantly increased in VSMC pretreated with intrinsically photoreactive nifedipine. A protein kinase C inhibitor staurosporine, added to the incubation medium, significantly reduced the enhanced specific photolabelling after ET-1. The increase in specific photolabelling after ET-1 preincubation (+197 +/- 46%; P < 0.05) was also observed in rings of the rat aorta and it was significantly reduced after preincubation with S-(+)-niguldipine.

Disposition of lypophilized (methylmethacrylate-14C, 2-hydroxyethylmethacrylate, butylacrylate) nanoparticles in rats and their effect on zoxazolamine paralysis time.

The fate of lyophilized (methylmethacrylate-14C, 2-hydroxyethylmethacrylate, butylacrylate) nanoparticles was studied in male Wistar rats after p.o. administration. It was found that at least 4% of the dose of 14C was absorbed from the gastrointestinal tract after a single dose with these nanoparticles. Some radioactivity (less than 0.15% of dose) was found 7 d after administration in lung, spleen and liver. As expected excretion of the label was predominated via the feces. Ten d of p.o. treatment of rats with lyophilized nanoparticles (1 g/kg of body weight) was shown to prolong significantly zoxazolamine paralysis time. This result suggests that lyophilized nanoparticles decreased elimination of zoxazolamine.

Fate of 14C-terpolymer (methylmethacrylate-14C, 2-hydroxyethylmethacrylate, butylacrylate) nanoparticles after peroral administration to rats.

The fate of 14C-terpolymer (methylmethacrylate-14C, 2-hydroxyethylmethacrylate, butylacrylate) nanoparticles was studied in male Wistar rats after peroral administration. These nanoparticles may reach systemic circulation as evidenced by the plasma 14C level, excretion of the label in the urine, as well as organ label deposition. It was found that at least 2% of the dose of 14C was absorbed from the gastrointestinal tract. As expected, the radioactive nanoparticles were excreted predominantly via the feces. The amount of the label in the gastrointestinal tract, liver, and carcasses fell below the limit of detection on day seven after administration. However in the spleen and lung some slight radioactivity persisted after 7 d of experiment.

Pharmacokinetics of ethimizol in man.

The pharmacokinetics of ethimizol were studied in healthy volunteers given 1 mg/kg i.v. or 2 mg/kg orally. The serum concentrations of ethimizol were determined by HPLC. After i.v. infusion the kinetics of ethimizol could be described by a one-compartment model in 4 and by a two-compartment model in 1 subject. The elimination half-lives ranged from 34.1 to 79.2 min and the apparent volumes of distribution from 0.4 to 1.3 l/kg. After oral administration, the absorption half-lives ranged from 7.3 to 57.1 min. The absolute bioavailability varied between 3.6 and 22.2%. The binding of ethimizol to plasma proteins was less than 10%.

The distribution in mice of intravenously administered labelled Candida albicans.

The time dependence of the distribution of intravenously injected radiolabelled Candida albicans in the body of mice was studied. The Candida cells were labelled by cultivating them 7 days at 28 degrees C in a medium containing one of the following radionuclides: 46Sc, 95Nb, 59Fe, 144ce, 89Sr, 60Co, 65Zn, 54Mn, 45Ca, 51Cr and 91Y, which are listed in decreasing order in respect to amount bound. The labelled cells were killed by heating them 120 min at 60 degrees C, without loss of immunologic properties. Owing to the amount and strength of binding, 144Ce labelled Candida, together with 14C labelled cells was used in animal kinetic study. A rapid disappearance of the labelled cells from blood, interrupted by a small peak, was paralleled by a transient uptake in lungs and followed by a long lasting accumulation in the liver. The kidneys and spleen revealed only small uptakes of the labelled material.

Kinetics of 131 I-o-iodohippurate in rats.

The organ distribution of 131I-o-iodohippurate (OIH) was studied in rats in the time interval of 1--1440 min. The mean decrease of OIH in plasma was fitted with a function composed of three exponential terms. A three-compartment model describing kinetics of OIH in rats was suggested and its parameters were computed. Comparison of organ and plasma concentrations of OIH showed that the liver, up to 30 min, and the heart and lungs, up to 15 min after administration, form with plasma a common central compartment.