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Fumaric acid monoethylester (FAME) inhibits the incorporation of 14C-Thymidin, 14C-Uridin, 14C-Alanin and 14C-Leucin into acid-insoluble biopolymers of cultivated PHA-stimulated human lymphocytes. At high concentrations of FAME (500 mug/ml culture medium) the inhibition of nucleic acid synthesis is 6 times higher on the average than the inhibition of protein synthesis. However, the application of the cis-isomer, maleic acid monoethylester (MAME), results in an increase of the incorporation rate of the labelled precursors into the RNA and DNA. This is 3.5--9.3 times higher than after application of FAME. The results demonstrate the specific inhibition by FAME. The rate of labelling of nucleic acids is decreased above 10 mug FAME/ml culture medium and in the case of MAME above 50 mug/ml medium. As an explanation of the specific action of FAME its influence on the enzymes of the nucleic acid synthesis, the citric acid cycle or a faulty synthesis of enzymes are discussed.

The incorporation of 14C-Thymidin into DNA of cultured human lymphocytes is depressed by added fumaric acid monoethylester (FSME) depending on the dosage of FSME. The decreased radioactivity in DNA as measured by scintillation counting is paralleled by a concomitant decrease in the labelling index in autoradiograms. Decreasing radioactivity is therefore due to a lower number of DNA synthesizing cells. No selective inhibition of proliferation during one of the cell cycle phases was observed. Especially a G2-block known from other cytostaties is absent. A mean dosis of 6.88 mg FSME per g body weight administered intraperitoneally is lethal to mice. The animal die from diffuse necroses of heart muscle cell. Alterations of other organs are less prominent. At lower doses of FSME the morphology of the organs investigated is altered to a smaller degree.

In vitro experiments have shown that the solubility of human enamel in decinormal solutions of malic, lactic, tartaric and citric acid was in most cases reduced by treatment with a 2.5% aqueous solution of disodium beta-glycerophosphate.

gamma-Glutamyltransferase is a membrane-bound enzyme widely distributed in animal tissues. This enzyme is involved in glutathione metabolism, but its exact biological function is still an open question. In rat brain cells in culture a depletion of L-cystine and L-glutamine or the addition of diethyl maleate to the culture medium leads to a decrease of intracellular glutathione concentration and to an increase of the specific activity of gamma-glutamyltransferase. The induction of the enzyme is inhibited by the addition of cycloheximide or actinomycin D to the culture medium.

Rats exposed to halothane (100 ppm) in a closed allglass-system eliminate halothane from the atmosphere of this system with a half-life (t0.5) of 0.99 h. In 24 h-fasted rats t0.5 was prolonged to 1.24 h. A single oral load of 4.8 g/kg ethanol as well as a 15% ethanol solution instead of drinking water for 28 days did not alter the metabolic elimination of halothane. On the other hand, ethanol (4.8 g/kg p.o.) applied 5 min before exposure to halothane markedly prolonged t0.5 to 3.79 h. Pretreatment with phenobarbital (80 mg/kg i.p. for 4 days) shortened t0.5 significantly to 0.79 h. Inhibition of the mixed-function oxidase system by dithiocarb (100 mg/kg i.p.) or diethyl maleate (1 ml/kg i.p.) markedly prolonged t0.5 to 7.53 and 1.57 h. respectively. The observed modifications of the halothane metabolism may be of interest in relation to the problem of halothane-induced hepatotoxicity.

Rats exposed to enflurane (100 ppm) or methoxyflurane (300 ppm) in a closed all glass-system eliminated these anesthetics from the atmosphere of the system with a half-life of 6.84 h for enflurane and 0.64 h for methoxyflurane. 24 h-fasting had no influence on these elimination half-lives. An oral load of ethanol (4.8 g/kg p.o.) only prolonged the half-life for methoxyflurane. Pretreatment with diethyl maleate (1 ml/kg i.p.), dimethylsulfoxide (DMSO, 1 g/kg i.p.) or dithiocarb (100 mg/kg i.p.) prolonged the elimination half-life of both enflurane and methoxyflurane. An accelerated metabolic elimination was only observed in DDT-pretreated rats exposed to enflurane; other inducers of the microsomal mixed-function oxidase system like phenobarbital or rifampicine had no significant influence on the in vivo metabolism of both enflurane or methoxyflurane.

The effect of several drugs on minipigs was examined over a period of upto 3 months. The drugs applied were: ethanol, etacryn acid (per os), ethanol, maleic acid, physiological NaCl--solution (by infusion). The creatinin-, uric acid-, lactat- and haematocrit-values of the serum and blood as well as the creatinin- and uric-excretion were followed. For ethanol and maleine acid an increase of the creatinin- and uric acid-excretion was found. This was accompanied by an increase of the haematocrit value. If the diuresis was augmented by certain substances, a more or less pronounced uricosuria was found. The measured values will be discussed, especially how the renal function may be involved.