Studies on the metabolism of l-asparaginic acid (author's transl)]

After infusion of DL-asparaginic acid (Inzolen) during operation the pharmacokinetics of L-aspartic acid were followed by means of enzymatic determinations in serum and urine samples. The level of L-aspartic acid in the serum increases during the infusion of 250 ml of Inzolen-Infusion (18.54 g DL-aspartic acid) from an original value of 2 mg/l to a maximal value of 156 mg/l, reached at the end of the infusion. Two hours after the termination of infusion, the aspartic acid level returns almost to its original value. Only 20% of the infused L-aspartic acid is excreted unmetabolized.     

Studies on the relationship between the endotoxin induced fever and the antipyretic effect of reserpine in rabbits (author's transl)]

It has been well documented that fever could be mediated with endogenous pyrogen released from reticuloendothelial system(RES) by administration of bacterial endotoxin(LPS) intravenously to rabbits. On the contrary, reserpine which has various pharmacological activities by depleting catecholamines decreases the normal body temperature as well as endotoxin induced fever. In this paper, we focussed our attention on the effect of reserpine on the production of endogenous pyrogen with relation to the antipyretic effect in endotoxin fever and obtained the following results: Endogenous pyrogen could be detected by intravenous administration of LPS(0.5 micrograms/kg) during the fever. However, endogenous pyrogen was undetectable with intracisternal administration of LPS(0.01 microgram/body) which provoked long-lasting fever. Reserpine (1 mg/kg, i.v.) decreased both body temperature induced by intracisternal administration of LPS(0.01 microgram/body) or intravenous administration of LPS(0.5 microgram/kg), however the degree was more extensive in cases of LPS-induced fever. Pretreatment of rabbits with reserpine (1 mg/kg, i.v.) suppressed the fever induced by an intravenous administration of LPS(0.5 microgram/kg), but did not suppress the release of endogenous pyrogen. These data suggest that endogenous pyrogen may not be an important factor in the pathogenesis of endotoxin fever.     

Studies on the effect of oxprenolol on experimentally induced anxiety (author's transl)]

This experiment studied the question of whether the receptor blocking agent oxprenolol (20 mg) influences somatic and subjective responses to experimentally induced anxiety. 72 male students were Ss in a two-factorial design with type of drug (oxprenolol, placebo) and type of situation as the two factors. Anxiety was induced by the signaled application of shocks to one arm, under condition A with and under condition B without time control (clock available or not). Condition C was a control condition with neither shock nor time control. Heart rate, blood pressure and verbal reports of emotional experience were measured. An analysis of variance revealed the following: Oxprenolol showed physiological effects typical of a receptor blocking agent. The drug positively affected emotional experience not related to the experimentally induced anxiety but did not affect the emotional responses induced by the anxiety-provoking conditions. For explaining the results the possible meaning of the variable "internal vs external control of emotional responses" was considered.     

Studies on metabolism and pharmacokinetics of alpha-acetyldigitoxin in man (author's transl)]

3H-alpha-Acetyl-digitoxin was administered to 5 patients i.v. and 3 patients p.o. The half-life of label in the plasma was 8.5 +/- 1 (i.v.) and 8.8 +/- 1 (p.o.) days. 20.9 +/- 3.6% (i.v.) and 21.3 +/- 2.9% (p.o.) of the radioactive dose were excreted into the urine in 6 days. Two patients excreted within 18 days 14.3 and 16.1% of the given dose with the stool. After oral administration 22.3% of the orally administered 3H-activity were eliminated into the feces by one patient. 63% (i.v.) and 53% (p.o.) of the chlorofrom-extracted 3H-activity in the urine could be attributed to digitoxin by means of thin-layer chromatography. The volatile content of plasma radioactivity was 4.07 +/- 0.1% (i.v.) and 6.78 +/- 0.2% (p.o.). The protein binding of a 4%. Albumin solution was 83 +/- 0.54%, for plasma 80.8 +/- 2%.     

Pharmacokinetics and metabolism of trazodone in man (author's transl)]

After intravenous, intramuscular and oral administration of 25 mg 14C-labelled 2-(3-[4-(m-chlorophenyl)-1-piperazinyl]-propyl)-s-triazolo[4,3-a]pyridin-3-(2H)-one-hydrochloride (trazodone), plasma levels, elimination and metabolite pattern in plasma and urine were investigated. The plasma levels after all routes of administration are almost identical. The absorption of the compound is fast and complete. The elimination of radioactivity occurs in a biphasic manner with a half-life of 1 h for the earlier and 13 h for the second phase, no matter what application route had been chosen. The comparison of the plasma levels of fasted and non-fasted subjects shows a shift of the plasma maximum from 1.5 to 2.5 h following administration and a decrease in the maximum level of 30%. The radioactivity is excreted predominantly by renal processes (70-75% within 72 h). The main product in plasma is unchanged trazodone, whereas in urine it is found only in minute amounts. The radioactivity in urine is represented by conjugates that had formed after hydroxylation on the chlorophenyl residue (20%), by a dihydrodiol-metabolite of trazodone (15%) and by a carboxylic acid originating from oxidative cleavage of the parent compound (35%).     

Studies on the metabolism and distribution of 14C-sodium nitroprusside in rats (author's transl)]

Studies on the in vivo degradation of 14C-labelled nitroprusside (NP) were conducted in rats and indicated that the primary product was cyanide and not thiocyanate. With the administration of higher doses of sodium nitroprusside (NNP; Nipruss) cyanide, thipcyanate, Fe++ and Fe+++ were evident in the blood plasma, whereas [Fe(CN)6]4- and [Fe(CN)6]3- were not detected. The biological half-life for the disappearance of nitroprusside was about 2 min with a dose of 0.4 mg NNP/kg and was 28 min with a dose of 6.25 mg NNP/kg. Nitroprusside and its degradation products, cyanide and thiocyanate, were eliminated mainly in the urine. Significant accumulation of nitroprusside did not occur either in blood vessel walls, in smooth muscles, or in parenchymal organs.     

Alcohol absorption and elimination in different alimentary conditions (author's transl)]

The continuous enzymatic in vivo estimation of blood alcohol was used for plotting curves of blood alcohol concentrations in 24 double-experiments from 4 to 6 h duration. Absorption and elimination of alcohol were observed under the influence of the food eaten before. Two hours after a light meal test persons drank whisky and blood alcohol curves were recorded determining increase, maximum and elimination. The curves varied especially in the phases of absorption. In a second test compared with the curves after a light meal the retardation of absorption was examined after drinking the juice of "Sangritta picante" spice in addition. Delayed alcohol absorption could be verified. After taking a fat meal the retardation of absorption was found even greater. Recorded after fasting for more than 12 h the curves showed a slower increase in blood alcohol concentration and a higher maximum in comparison with the curves after a light meal.     

The antipyretic effects of aminopyrine and sodium acetylsalicylate on endotoxin-induced fever in rabbits (author's transl)

The antipyretic effects of aminopyrine and sodium acetylsalicylate on endotoxin-induced fever in rabbits were studied relative to the route and dose of administration. Intravenous administration of aminopyrine produced a marked antipyretic effect, intracisternal administration produced a lesser effect and i.v. was the effective route. Similar results were obtained in the nonfebrile rabbits. On the contrary, the intracisternal administration of sodium acetylsalicylate reduced the body temperature to the same degree both in febrile and nonfebrile rabbits, but sodium acetylsalicylate given i.v. to nonfebrile rabbits did not reduce the body temperature. 4-aminoantipyrine and N-acetyl-4-aminoantipyrine, the major metabolites of aminopyrine had a lesser effect in the febrile rabbits. Antipyretic effects of sodium salicylate, the metabolite of sodium acetylsalicylate were similar to the effects of sodium acetylsalicylate. These data suggest that the antipyretic effects of aminopyrine may not be involved in the CNS, while the antipyretic effects of salicylate may be due to a direct action on the CNS.     

Studies on the antimicrobial effect of natural and synthetic humic acids (author's transl)]

Preparations of humic acids extracted from different soils by various methods and model humus substances obtained synthetically by oxidation of hydroquinone and pyrocatechin are tested for growth inhibition of representative strains of human pathogenic microorganisms using a micro serial dilution technique. Within the concentration range of less than or equal to 2500 micrograms/ml 57 of 81 natural and also the two synthetic humic acids show antimicrobial activity with differing spectra. These substances inhibit St. epidermidis, St. aureus, Str. pyogenes, S. typhimurium, Prot. vulgaris, Ent. cloacae, Ps. aeruginosa and C. albicans, but not Str. faecalis and E. coli. The degree of activity or the sensitivity of test organisms, respectively, amounts to 2500--1250 micrograms/ml predominantly, partially 625--312 micrograms/ml and can reach values of up to 39 micrograms/ml with synthetic hydroquinone humic acid. The spectrum and degree of activity vary according to the origin and extraction mode of the natural humic acids. The in vitro evidence of efficiacy against human pathogenic microorganisms gives a rational basis of therapeutic use of substances of humic acid type in infectious conditions.