Urinary elimination kinetics of pyrimethamine.

In this study, the kinetics of pyrimethamine elimination via the urine was investigated. The experiments were carried out on six healthy male volunteers aged 23-32 years. The drug was administered orally (p.o.) in a single dose at three different concentrations i.e.: 50, 75 and 100 mg. The concentration of the drug in the urine was determined via the modified method of Bonini et al. and Garber et al. It was found that 13.4 +/- 1.3% of the dose eliminated via the urine was in unchanged form. The process of pyrimethamine elimination may be described according to an open kinetic two-compartmental model: the formula showing the course of pyrimethamine elimination over time has been given. Several examples of the quantitative exposure test have been proposed, which allow the calculation of the drug dose absorbed and thus the degree of toxicity to be determined. This test can also be useful in a controlled clinical setting.

Kinetics of pyrimethamine in young and adult rats on a standard diet and on a low-protein diet.

A pharmacokinetic study of pyrimethamine was carried out in 4- (103-115 g) and 12-week-old (260-280 g) white male Wistar rats fed a standard diet containing 24% protein, and a low-protein diet containing 8% protein. After intragastric administration of the drug in a single dose of 40 mg/kg body weight, the concentrations of pyrimethamine in the blood were determined at different time points from 15 min to 20 hours post-dose. On the basis of the results obtained, a number of parameters characterizing the course of absorption and elimination of the drug from the blood were calculated. The majority of parameters were dependent on both age and type of diet. The greatest bioavailability was observed in the 4-week-old rats: for the animals fed the low-protein diet, the area under the concentration-time curve (AUC) amounted to 593.0 and for those on the standard diet the AUC was 503.1. In the older rats, this parameter was 339.3 and 228.1 respectively. The k(e) values were lower in the younger rats (i.e. 0.0121 h(-1) and 0.0135 h(-1)) than in the older animals (i.e. 0.0164 h(-1) and 0.0193 h(-1) respectively). The elimination half-life (t1/2) was higher in the 4-week-old rats (i.e. 57.1 h; 8% protein, and 51.2 h; 24% protein) than in the 12-week-old animals (i.e. 42.4 h; 8% protein, and 36.0 h; 24% protein).

[Exposure of inhabitants of Poznan to fluorides. I. Fluorides in atmospheric air, tap water and selected additional fluids]. / Narazenie mieszkanców Poznania na fluorki. Czesc I. Fluorki w powietrzu atmosferycznym w wodzie wodociagowej oraz w wybranych plynach uzupelniajacych.

The purpose of the study was to obtain information about fluoride pollution of the human environment. Fluoride concentrations were measured in atmospheric air, water and certain drinks. The measurements were done with a ion-selective electrode. In the atmospheric air of Poznan and its environs the concentrations ranged from 0.0006 mg/m3 to 0.0122 mg/m3. Tap water in Poznan contained 0.2 mg F3/dm3, on average. The selected drinks--mineral water and tea contained 0.3 and 1.5 mg F-/dm3 respectively. The acceptable values of fluoride concentrations were not exceeded, but fluoride concentration in atmospheric air was higher than that found usually in other regions of the country. In drinking water fluoride concentration in Murowana Goslina was within the acceptable range, and in Poznan it was twice lower.

[Exposure of Poznan inhabitants to fluorides. II. Fluorides in urine and hair of school children]. / Narazenie mieszkanców Poznania na fluorki. Czesc II. Fluorki w moczu oraz wlosach dzieci szkolnych.

In view of the plans of fresh water fluoridation in Poznan the necessity arose of obtaining of information about the exposure to fluoride compounds. The reported study was carried out in Poznan and environs. Urine and hair samples of children were obtained. The determinations were done with a ion- selective electrode. The mean fluoride concentrations in urine were between 0.3 and 0.9 mg F-/dm3. The concentration in hair was 2.2 mg F-/g in Poznan and 3.3 mg F-/g in Lubon. These values were, however, not exceeding the acceptable ones. In Lubon the concentrations of fluorides in hair was 50% higher than in Poznan. The authors believe that the possible cause was Fertilizer Chemical Works in that location.

Retardation of lung development after maternal cigarette smoking and low protein diet in animal model.

This study has been aimed at showing the influence of tobacco smoke, together with low protein diet on the lungs of newborn rats. The studied animals were Wistar rats. They were exposed to the tobacco smoke for 11 weeks (6 weeks before mating, 12 days during mating, and 21 days of pregnancy). Morphological analysis and interpretation of 48 one-day old rats was based on observation under the light and electron microscope. The study showed atelectasis of the lungs: the lung tissue was insufficiently extended, the alveoli were geometrically irregular and the alveolar septa were thick. Many extravasated erythrocytes and edema (latent as well as overt) were also present. The II type pneumocytes and their surfactant were poorly developed. Tobacco smoke caused the serious pathological effects and together with poor protein diet all changes worsened. For comparison, the lungs of control group were studied (lack of exposure to tobacco smoke); they were well aerated and their structure well-developed.

Studies on kinetics of sulfadiazine and trimethoprim excretion in man.

The kinetics of sulfadiazine and trimethoprim excretion was determined. The examinations were performed on 10 healthy people. The compounds were given orally once, in the form of pure substances, applying three different doses: 80, 240 and 720 mg of sulfadiazine and 20, 60 and 180 mg of trimethoprim. In order to estimate the contents of sulfadiazine in urine, Bratton-Marshall's method was applied while the colorimetric method according to Vachek and Kakac was used in estimating the contents of trimethoprim. This method was adapted by Klimowicz to determine trimethoprim in blood and it was modified in our laboratory. It was stated that about 44 per cent of the administered dose of sulfadiazine and about 56 per cent of trimethoprim were excreted with urine in the form of unchanged compounds. The excretion processes of both compounds can be described in the way accepted for one-compartment kinetic models. The value of the half-life of sulfadiazine excretion is 8.4 hours while that of trimethoprim is 6 hours. The constant of loss is 0.083 for sulfadiazine and 0.118 for trimethoprim. The given formulae allow to calculate the rate of excretion of sulfadiazine and trimethoprim with urine at any time after being administered. The tests proposed to calculate the accepted drug doses, which are based on measuring the excretion rate of the unchanged substances with urine, so that they may be applied in controlled therapy and in poison therapy.

[Toxicodynamic properties of liquids used for the cooling of high-power turbines. III. Neurotoxic effects]. / Toksykodynamiczne wlasciwosci cieczy stosowanych do chlodzenia turbin wysokiej mocy. III. Dzialanie neurotoksyczne.

Results of neurotoxicity studies indicate that preparations IWiOL -3-n, IWiOL -3-e and OMTI administered intragastrically or intraperitoneally induce neurotoxic effects in hens. Those effects are, however, weaker than those of the standard substance, i.e. triorthocresyl . Yet, they get increased in result of IWiOL -3-e, as compared to IWiOL -3-n administration.

[Toxicodynamic properties of liquids used for cooling high-power turbines. I. Acute, subacute and chronic toxicity]. / Toksykodynamiczne wlasciwosci cieczy stosowanych do chlodzenia turbin wysokiej mocy. I. Toksycznosc ostra, podostra i przewlekla.

Oils IWiOL-3 and OMTI are used to cool the high-power turbines. Their toxicodynamic properties are little known, therefore the studies described herein have been undertaken. The studies did not reveal high acute toxicity, as A-DL50 was found to exceed 15 g/kg of body weight. The simultaneous measurements of cholinesterase activity demonstrated its clear decrease, The studies of subacute toxicity after Lim showed that OMTI after a year's exploitation is the most toxic fluid, as C-LD50 for this compound is 6,21 g/kg of body weight, whereas C-LD50 for the other oils is: 22.449 g/kg of body weight for IW i 02-3-n and 20.93 g/kg of body weight for IWiOL-3-e. Studies of chronic toxicity showed decreased cholinesterase activity and no significant changes in the measurements of certain biochemical and haematological. indices.

[Toxicodynamic properties of liquids used for cooling high power plants. II. Toxicity determined by inhalation and dermal routes]. / Toksykodynamiczne wlasciwosci cieczy stosowanych do chlodzenia turbin wysokiej mocy. II. Toksycznosc okreslona droga inhalacyjna i dermalna.

In experiments on toxicity, IWiOL-3-n aerosol as well as vapours and gases obtained by heating the oil up to 500 degrees C were administered by inhalation to experimental animals. No deaths of animals were recorded however, a significant decrease of cholinesterase activity was noted. The experiments were carried out in the specially constructed experimental chambers and the method of determination IWiOL-3-n in the air was developed. After intratracheal insufflation of IWiOL-3-n, rapid decrease of cholinesterase activity in blood serum was also observed. Tests on dermal toxicity showed very good absorption of the oils through the untouched skin.

[Study of the relationship between pulmonary changes and blood plasma composition under the effect of industrial dust. III. Usefulness of the results of the studies for diagnostic purposes]. / Poszukiwania wspólzaleznosci miedzy zmianami w plucach a skladem osocza krwi pod wplywem pylów przemyslowych. CZ. III. Uzytecznosc wyników badan dla celów diagnostycznych.

The paper presents results of statistic calculations enabling to define the diagnostic usefulness of results of determining free aminoacids in blood plasma for evaluation of workers' exposure to grinding and ceramic dusts and welding fume. Determination of proline in the blood plasma of ceramic industry workers and electric welders and determination of hydroxyproline in welders' blood plasma were found to be a particularly significant and early index of exposure to ceramic dust or welding fume.