Showing papers in "Acta vitaminologica et enzymologica in 1978"

Ascorbic acid therapy for the relief of bone pain in Paget's disease.

Abstract: Sixteen patients with painful Paget's disease of the bone were treated with high doses of ascorbic acid. Of these patients, 8 experienced lessening of pain within a period of 5 to 7 days after commencing the vitamin therapy. In 3 of these patients pain was completely abolished. Subsequent treatment with calcitonin caused improvement in most cases. There was little change in plasma alkaline phosphatase levels but the excretion of hydroxyproline was elevated following administration of the vitamin. The highest excretions were found in those patients who experienced complete relief of pain. In patients treated with calcitonin alone, the excretion of hydroxyproline was reduced and urinary levels of ascorbic acid dropped in parallel. It seems clear that ascorbic acid and calcitonin have different effects upon bone metabolism.

A further contribution to the choice of the dose for L-tryptophan load test.

Abstract: The analysis of the results of a study on the urinary excretion of metabolites "via kynurenine" after the ingestion in man of different amounts of tryptophan is reported. Of the three doses of L-tryptophan administered to the subjects, that is 2 g pro capite, 50 mg/Kg and 75 mg/Kg body weight, it is preferable to choose that of 50 mg/Kg b.w. as a load test. Such a dose assures an excretion of the more important metabolites without significant variations between men and women and without producing overloading effects.

On the regulation of tryptophan metabolism "via" kynurenine.

Abstract: The tryptophan leads to nicotinic acid pathway is inhibited in the nicotinic acid administered rats; in this case tryptophan chiefly metabolizes "via" serotonin. The serotonin pathway is inhibited in the excess phenylalanine administered rats, especially due to the inhibition of the tryptophan-5-hydroxylase reaction. Xanthurenic acid inhibits kynurenine-3-hydroxylase in vitro, which is a very important regulatory enzyme for xanthurenic acid and nicotinic acid production.

Regulation processes in biological systems. II. Role of compartmentation and of organized multienzyme systems

Abstract: The picture, emerging from the experimental results on the physical association of multienzyme systems, is that the true physiological significance of the aggregated state can be understood only if it is correlated to the structural and functional integration of the cellular metabolic framework as a whole. The enzyme clusters exhibit two distinct functional properties. The first is the spatial translocation of intermediate substrates, the effect of which may be viewed as metabolic "channelling" or "vectorial catalysis" if the enzyme clusters are arrayed in some manner in the cell. The second is the coordinate regulation which represents an efficient and economical mean of controlling two or more functionally related enzymes. The common element to these two properties is the spatial character, which is potentially present in the function and the regulation of the intermediary metabolism. The biological systems, and metabolism in particular, exhibit both stability and variability; the latter sometimes assumes the character of periodicity. Whether the oscillations have a definite importance at the level of the intermediary metabolism itself, may well be questioned; the oscillatory faculties may rather serve as elements to be used in more complex functions of the biological systems. A thorough understanding of the role of clustered multienzyme systems and of the oscillatory phenomena in cellular metabolism demands a clearer physicochemical picture of the dynamic state of the living cell than we have at present. For this reason some of the generalizations derived from in vitro studies of single, isolated enzyme activities are not justified.

The spontaneous urinary excretion of tryptophan metabolites "via kynurenine" in women with regards to the prepuberty, sexual maturity and menopause.

Abstract: High values of anthranilic acid, 3-OH-kynurenine, xanthurenic acid and 3-OH-anthranilic acid are observed in the spontaneous urinary excretion of tryptophan metabolites in girls in the prepubertal age. The highest differences are between the 3-hydroxy metabolites especially the 3-hydroxykynurenine. On the other hand, this metabolic excretion in postmenopausal women is statistically identical to that of women in sexual maturity.

The effect of allopurinol on the kynurenine formation in humans following a tryptophan load.

Abstract: The effect of allopurinol on the kynurenine formation in three manic depressive patients, two in remission and on in depression, has been studied during long-term treatment with L-tryptophan. The patients were loaded with 100 mg L-tryptophan per Kg body weight prior to and after one week on allopurinol, 300 to 500 mg per day. The area under curve (AUC) of plasma total and free tryptophan increased slightly in the patients in remission but not in the depressive. The former showed no change in the AUC of plasma kynurenine whereas an increase was seen in the depressive. The results suggest that allopurinol does not inhibit the human tryptophan pyrrolase definitely during loadings with L-tryptophan.

Effect of vitamin D and vitamin E on the erythrocyte membrane. I. Effect on in vitro osmolar resistance and lysis

Abstract: As in the case of retinol, low doses of cholecalcipherol and alpha-tocopherol "in vitro" increase the osmotic resistance of red blood cells, while high doses have a lytic effect on the erythrocytes of various animal species (e.g.: man, sheep, rabbit, guinea-pig, mouse, rat) with the exception of the chicken. The haemolytic effect of cholecalcipherol is less intense than that of retinol; alpha-tochopherol, while causing even less haemolysis than cholecalcipherol, involves a remarkable loss of K+ from the red cells. Besides these quantitative differences, the mechanism of action of the three vitamins seems somewhat different, as shown by modifications of the suspension medium (e.g.: pH, temperature, presence of proteins and reducing substances) or by treatment of the red cells with trypsin. Our results therefore essentially confirm the hypothesis of Dingle and Lucy of common mechanism of action of liposoluble vitamins on biological membranes.

Toxicity and tolerance of tryptophan and its metabolites

Abstract: For the therapeutic use of tryptophan it is necessary to know its toxicity and pharmacological effects; but very few data are reported in literature on these aspects. On the other hand there are many researches on tryptophan metabolism after a load test and related side effects. From these data it appears that a tryptophan dose of 100 mg/Kg body weight per os is usually well tolerated with exception of some short and slight gastric troubles (vomit, etc.). The lack of references to repeated and long lasting administrations (chronic toxicity) and of a therapeutic index must be filled. Side effects due to a single dose of 5.OH-tryptophan, e.g. head twitches, resemble those due to serotonine. With regard to the most important metabolites of the kynurenine pathway, the available data have been obtained with kynurenine and especially with xanthurenic acid. These compounds have a low toxicity and do not appear to have important pharmacological properties. However, systematic researches are necessary before using these compounds either in load tests or for therapy in man.

In vitro studies of the effect of metal ions, EDTA and their mixtures on kynurenine aminotransferase and kynurenine hydrolase.

Abstract: In the present study use was made of the chelating ability of EDTA and the activating property of some metal ions Ca(II), Mg(II) or Mn(II) to counteract the inhibitory effect of Cu(II), Co(II), Pb(II) or Zn(II) ions on the B6-dependent kynurenine hydrolase and on kynurenine aminotransferase. These may be of help in studying the therapeutic trials in the treatment of metal poisoning. EDTA was able to counteract the inhibitory effect of Cu(II) or Co(II) on kynurenine aminotransferase and partially counteract the inhibitory effect of Cu(II), Co(II) on kynurenine aminotransferase and partially counteract the inhibitory effect of Cu(II), Co(II), Pb(II) or Zn(II) ions on kynurenine hydrolase. The difference in the response of the two B6-dependent enzymes to EDTA is attributed to the difference in the functional groups involved in the active site(s) of the two apoenzymes. Moreover, Mn(II), Ca(II) and Mg(II) ions have the ability to counteract some of the inhibitory effect of these metal ions.