On the problematic nature of vitamin E requirements: net vitamin E.

The requirement for vitamin E is closely related to the dietary intake of polyunsaturated fatty acids (PUFA). By the protective mechanism to prevent PUFA from being peroxidized, vitamin E is metabolically consumed. In addition, PUFA impair the intestinal absorption of vitamin E. Therefore PUFA generate an additional vitamin E requirement on the order of 0.6, 0.9, 1.2, 1.5, and 1.8 mg vitamin E (RRR-alpha-tocopherol-equivalents), respectively, for 1 g of dienoic, trienoic, tetraenoic, pentaenoic, and hexaenoic acid. For this reason, the gross vitamin E content of food containing PUFA does not allow an evaluation of this food as a source of vitamin E. A suitable measure is the net vitamin E content, i.e., gross vitamin E minus the amount needed for PUFA protection. Therefore, some food-stuffs generally considered as vitamin-E sources, as concluded from their gross vitamin E content, cause in reality a vitamin E deficiency if not sufficiently compensated by other vitamin E supplying food constituents. Examples of the net vitamin E content of some fats and oils, fish and nuts are shown. Consequences for food composition data and food labeling and the problem of meeting the vitamin-E requirements are discussed.

[L-tryptophan and the eosinophilia-myalgia syndrome--consequences for artificial nutrition?]. / L-Tryptophan und das Eosinophilie-Myalgie-Syndrom--Konsequenzen für die künstliche Ernährung?

Present knowledge on the possible cause of the tryptophan-induced eosinophilia-myalgia syndrome is discussed on the basis of a literature survey. The initially favored hypothesis of metabolites of a deranged tryptophan metabolism in some persons as cause of the syndrome has no plausibility for several reasons discussed in this paper. In the meantime trace backs of implicated tryptophan lots have led to one manufacturer who has changed his production procedure. The implicated lots contain a variety of impurities detectable by HPLC. Whether these impurities are the immediate cause of the syndrome or just markers remains to be established. An animal model suitable to clarify this question has recently been developed. Taking all these measures to identify and eliminate suspicious lots, there is no reason to withhold live saving artificial nutrition with tryptophan-containing preparations.

Crystalloid lysozyme inclusions in Paneth cells of vitamin A-deficient rats.

The effect of vitamin A-deficiency on jejunal Paneth cells in rats was investigated. Crystalloid particles were observed in secretion granules of Paneth cells from 6 out of 8 rats with vitamin A-deficiency. The particles were similar to those found in Paneth cells under other experimental conditions. Using an immuno-electron-microscopic technique we demonstrated a clear lysozyme immunoreactivity of these particles. In 2 vitamin A-deficient rats tubular structures have been detected in addition to the crystalloid particles. Crystalloid particles or tubular structures were not detectable in a control group of 8 vitamin A-supplemented rats. The morphological alterations of Paneth cells may be correlated to an impaired local immunity of the intestine during vitamin A-deficiency.

[Significance of vitamins in parenteral nutrition]. / Die Bedeutung der Vitamine in der parenteralen Ernährung.

Parenteral nutrition is incomplete without vitamins. Marginal vitamin deficiency under parenteral nutrition is certainly more common than generally recognized. Even marginal and undiscernable vitamin deficiency interferes with healing processes and increases the rate of complications since vitamins are involved in a variety of ways in wound healing, regeneration processes and immune function. If total parenteral nutrition is necessary for longer periods of time, exceeding 5 days, vitamins should be substituted in the recommended doses. The assessment of a marginal vitamin deficiency is difficult to perform and extremely expensive. It is therefore easier, safer and cheaper to substitute vitamins in total parenteral nutrition from the beginning, if preceeding malnutrition is likely. Recommendations for dosage and mode of application are reported and explained.

Uptake and metabolism of retinoic acid induces inhibition of cell growth: a study in a rat rhabdomyosarcoma cell line (BA-HAN-1C) using nonlinear theoretical models.

Retinoic acid causes a significant inhibition of cell growth of the tumor cell line BA-HAN-1C. This growth inhibition is the same whether the cells are treated with a pulse dose of retinoic acid (RA) or continuously expand to RA. The determination of RA and its degradation products within the culture medium and in the cells showed that after 24 hours 13-cis-RA was the major retinoid in all cells (96 ng/10(6) cells); all-trans-RA represented 56 ng/10(6) cells. After 48 hours 4-hydroxy-RA and a small amount of 5,6-epoxy-RA was found in the cells and also in the culture medium. 4-hydroxy-RA increased up to 96 hours, whereas 13-cis- and all-trans-RA were not detectable in the cells after 96 hours. We conclude that the BA-HAN-1C cells take up and metabolize RA. Nonlinear fit analysis of the time behavior of the RA concentration in medium demonstrates that the RA uptake unexpectedly follows a mono-exponential time function. Discussion of the experimental results in connection with a proper compartment model shows that uptake and metabolism of RA cannot be described really by a first order kinetics. The mathematical analysis leads to a more complicated kinetic model with certain restrictions for the corresponding rate constants.

[Metabolism of L-thiazolidine-4-carboxylic acid]. / Metabolismus der L-Thiazolidincarbonsäure-(4).

L-thiazolidine-(4)-carboxylic acid (TAC) has proven to be a good substrate for long-term parenteral nutrition. In this study the metabolism of TAC in the rat is examined at subcellular level. TAC is oxidized by mitochondrial proline oxidase of liver and kidney to L-thiazoline-(4)-carboxylic acid, which then is hydrolyzed to N-formyl-cysteine (FCYS). FCYS is hydrolyzed to cysteine and formic acid by a cytosolic enzyme.

Use and abuse of high dosages of vitamin B6.

Concepts of vitamin B6 megatherapy are classified in three categories: 1. megatherapy with well-known mechanism of action; 2. megatherapy with hypothetical or unknown, but nevertheless plausible mechanism of action; 3. megatherapy on the basis of pure speculation. Examples of all three categories are shown. The dosages applied extend from 100 mg up to several grams; the duration of treatment varies from weeks to several years. After long-term intake of high doses toxic effects can occur in the form of peripheral sensory neuropathy, in two reported cases combined with a subepidermal vesicular dermatosis. The threshold above which toxic effects can occur appears to be somewhat between 300 and 500 mg/day; however, systematic investigations in this dose range have never been performed. Furthermore, there appears to be an inverse relationship between the dose and the time up to the occurrence of toxic symptoms. The danger consists less in controlled application by a physician as far as he is aware of the clinical picture of sensory neuropathy. Doses in excess of 500 mg are rarely necessary in specific indications. Unlike this situation, self-medication by laymen on the basis of promises in obscure health magazines is much more risky because the dose is frequently raised more and more up to several grams per day when the expected effect does not occur.

Utilization of glutathione disulfide as cysteine source during long-term parenteral nutrition in the growing rat.

Utilization of intravenously administered glutathione disulfide was investigated during long-term parenteral nutrition in growing rats. In a series of cross-over studies, three solutions were tested against one another by recording weight gain, nitrogen balance, and plasma amino acid patterns. Solution 1 contained the required amount of methionine for rats, solution 2 had only one third of the required methionine, but was made isonitrogenous with glycine, whereas in solution 3, two thirds of the methionine was replaced by glutathione disulfide. Weight gain was about twice as high during infusion with either the required amount of methionine or the glutathione disulfide when compared with solution 2. Nitrogen retention was significantly higher during infusion with sufficient methionine or a corresponding amount of glutathione disulfide, when compared with the solution low in methionine. Plasma levels of cystine decreased significantly under the low methionine supply, but no difference was observed for the groups receiving sufficient methionine or the corresponding amount of glutathione disulfide. It is concluded that glutathione disulfide permits adequate cysteine supply in parenteral nutrition and may replace part of the methionine in the presence of an impaired conversion of methionine to cysteine.

[Evaluation of N-acetyl-L-tryptophan in long-term intravenous administration in growing rats]. / Die Verwertung von N-Acetyl-L-Tryptophan bei langfristiger intravenöser Verabreichung in wachsenden Ratten.

Utilization of N-acetyl-L-tryptophan as a source of L-tryptophan is tested in growing rats receiving total parenteral nutrition for twelve days. The three solutions tested are isonitrogenous and isocaloric. Solution 1 contains an adequate amount of L-tryptophan, while in solution 2 two thirds of the L-tryptophan are substituted by a corresponding amount of glycine. In solution 3, the entire L-tryptophan is replaced by N-acetyl-L-tryptophan. Weight gain and nitrogen balance are similar under the infusion with either the adequate amount of L-tryptophan or the N-acetyl-L-tryptophan. The solution 2 in which two thirds of the L-tryptophan are replaced by glycine yields significantly lower results for weight gain and nitrogen retention. The results indicate that tryptophan from N-acetyl-L-tryptophan, when given intravenously, is utilized by the rat for protein synthesis and growth as well as free tryptophan.

[Cysteine in parenteral nutrition: comparative study of N-acetyl-cysteine and N,N-diacetylcystine in the rat model]. / Cystein in der parenteralen Ernährung: Vergleichende Studien über N-Acetylcystein und N,N-Diacetylcystin am Modell der Ratte.

In this study the question of whether N-N-diacetylcystine (DAC), which is more stable than N-acetylcysteine (AcCYS), may provide a useful cysteine source for parenteral nutrition was investigated. In in vitro studies the release of cysteine from DAC was measured. The Michaelis, constant and maximum velocity were compared with the corresponding results for AcCYS. In in vivo studies 3 groups of growing rats were maintained entirely by parenteral nutrition low in methionine for 15 days. Group I (n = 4) received a solution containing AcCYS, and group II (n = 6) was supplied with a corresponding amount of DAC. In the solution given to group III (n = 6) the CYS derivative was replaced by an isonitrogeneous amount of glycine. Utilization of the respective CYS derivatives was judged from weight gain, nitrogen balance, plasma amino acid pattern, and urinary excretion of free amino acids. The results from both the in vitro and in vivo studies indicate that DAC is not a suitable substitute for AcCYS in parenteral nutrition.

[Serum vitamin A determinations and their value in determining vitamin A status]. / Serum-Vitamin-A-Bestimmungen und ihre Aussagekraft zum Vitamin-A-Status.

As demonstrated in the literature on vitamin A metabolism and homeostasis of retinol in serum, the concentration of retinol in serum is regulated very exactly if the liver stores are within the physiological range (20-300 micrograms/g liver). Therefore, the serum level indicates the status of vitamin A storage only if there is an extreme depletion or overconsumption of vitamin A. At marginal depletion, however, there is damage to peripheral tissue before changes in the vitamin A level in serum occur. At the beginning of hypervitaminosis A, changes in the level of vitamin A in serum also occur later. Therefore, the determination of vitamin A in serum gives no information on the adequacy of liver reserves for judging the necessity of a substitution.

Avarol-induced DNA strand breakage in vitro and in Friend erythroleukemia cells.

The hydroquinone-containing cytostatic compound avarol inhibits predominantly growth of those cell lines which have a low level of superoxide dismutase. The substrate of this enzyme, the superoxide anion, was found to be formed during the in vitro oxidation reaction of avarol to its semiquinone radical in the presence of oxygen. Under the same incubation conditions plasmid DNA (pBR322) was converted from the fully supercoiled circular form mainly to the nicked circular form, indicating that the compound causes primarily single-strand breaks. Using Friend erythroleukemia cells (FLC) it was found that avarol induces a dose-dependent DNA damage; the maximum number of DNA strand breaks was observed at 5 h after addition of the compound to the cells. Removal of avarol resulted in a rapid DNA rejoining with biphasic repair kinetics [first half-time, 8 min (90% of the breaks) and a second half-time, 40 min (10% of the breaks)]. When the degree of avarol-induced DNA damage in FLC was compared with the drug-caused inhibition of cell growth a close correlation was established. Avarol displayed no effect on dimethyl sulfoxide-induced erythrodifferentiation of FLC as determined by the benzidine reaction and by dot blot hybridization experiments. From incubation studies of FLC with [3H]avarol no hint was obtained for the formation of an adduct between DNA and the compound. The subcellular distribution of [3H]avarol was studied in liver cells after i.v. application of the compound. The predominant amount of the compound was present in the cytosolic fraction; little avarol was associated with plasma membranes, nuclei, and mitochondria. Using (a) oxidative phosphorylation and (b) oxygen uptake as parameters for mitochondria function, no effect of the compound on the activity of this organelle was determined. These results suggest that avarol forms superoxide anions (and in consequence possibly also hydroxyl radicals) especially in those cells which have low levels of superoxide dismutase. Moreover, evidence is provided that the active oxygen species cause DNA damage resulting in the observed cytotoxic effect.