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A Simmel

Publications and source records attributed to A Simmel.

11 recordsLinked to original sources
PubMed1989

Availability of glutamine from peptides and acetylglutamine for human tumor-cell cultures.

In a recent study we showed that the growth behavior of a hematopoietic cell line (K 562) in culture was the same when using glutamine-containing dipeptides or glutamine as substrate. In this article we study the growth behavior of different tumor cells, originating from the hematopoietic system (K 562), stomach (Kato III), pancreas (Panc 1), and breast (T 47 D), to test the biological activity as preclinical in vitro screening system. We compared L-glutamine (GLN), N-acetyl-L-glutamine (ACE-GLN), L-alanyl-L-glutamine (ALA-GLN), and glycyl-L-glutamine (GLY-GLN). Cell proliferation was measured with the incorporation of [3H] thymidine or the MTT assay (cleavage of 3-(4,5-dimethyldiazol-2-yl)-2-5-diphenyl tetrazolium bromide by mitochondria). In all investigated cell types cell growth was stimulated when using glutamine-containing dipeptides or ACE-GLN instead of a glutamine-free media (not significant for T 47 D). However, GLN or ALA-GLN was advantageous to GLY-GLN or ACE-GLN when measuring cell proliferation with the MTT-assay up to 72 hours. However, alanylglutamine does not enhance proliferation, compared with free glutamine.

Breast Neoplasms↗
PubMed1989

Glutamine-containing dipeptides as infusion substrates in the septic state.

Recently a relationship has been postulated between lowered intracellular glutamine concentrations in the skeletal muscle and the rate of protein synthesis. We investigated the effect of 48 hours of parenteral nutrition supplemented with a solution containing glutamine in free or dipeptide form (alanylglutamine or glycylglutamine) on the intracellular glutamine pool in skeletal muscle and on the hind limb exchange of glutamine in dogs with sepsis after surgery. Before surgery, dogs were fasted for 48 hours. We used glutamine dipeptides as sources because they remain stable in an aqueous solution. Nutrition solutions were isocaloric (17.8 kcal/kg body weight/day on day 1 and 35.6 kcal/kg on day 2) and isonitrogenous (0.33 gm nitrogen/kg body weight/day), providing 2.6 mmol/kg body weight/day as glutamine source. During starvation, muscular free glutamine levels decreased by 41% to 10.4 mmol/L (p less than 0.001). On the second postoperative day the dogs had lowered plasma protein levels, a sharp drop in platelet count, an increase in the leukocyte count, and positive blood cultures. None of the solutions investigated in this study was effective in repleting the glutamine pool during 2 days of postoperative nutrition (11 +/- 2.0 mmol/L without glutamine, 10.3 +/- 2.2 mmol/L with glutamine plus alanine, 9.9 +/- 1.6 mmol/L with alanylglutamine, 7.5 +/- 1.1 mmol/L with glutamine plus glycine, and 7.2 +/- 1.2 mmol/L with glycylglutamine, respectively). The release of glutamine from the hindquarter was 631 +/- 38 nmol/kg body weight/min in the control group and decreased significantly in dogs receiving alanylglutamine (13.5 +/- 45 nmol/kg body weight/min; p less than 0.001) or the constituent amino acids (265 +/- 66 nmol/kg body weight/min; p less than 0.01) but was unchanged in dogs receiving glycylglutamine or glutamine plus glycine. We conclude that the duration and dosage of glutamine administration (equivalent to 26 gm glutamine per day in a patient weighing 70 kg) used in this study are not sufficient to restore glutamine deficiency of the skeletal muscle in the depleted state.

Alanine↗
PubMed1989

[Selective effect of personality markers and psychosocial stress on T lymphocyte subpopulations].

Measurements were made of cellular immune system parameters in a group of healthy medical students. On the basis of psychosocial stress encountered during a five-day topic-centered self-awareness course, we investigated modulation in immunity in relation to personality characteristics. 6 days before the beginning of the seminar personality profiles were drawn and blood samples taken. Further immunological measurements were made on day four of the seminar and three weeks after its conclusion. On the fourth day of the seminar we observed throughout the group higher lymphocyte and suppressor/cytotoxic T lymphocyte counts in comparison with counts one week earlier, and likewise a heightened responsiveness to PHA- and IL-2 stimulation. The T lymphocyte counts had dropped. In subjects with a higher need for succorance/nurturance, the depression of the immune system was manifested in a drop in the helper/inducer T lymphocyte counts, and in the more achievement- and order-oriented subjects in a downregulation as observed by higher suppressor/cytotoxic T lymphocyte counts. Our results show that under psychosocial stress, healthy people experience on the one hand an activation of the immune system, and on the other hand an immunodepression bearing a specific relation to personality characteristics.

Adult↗
PubMed1988

Influence of two glutamine-containing dipeptides on growth of mammalian cells.

The instability of the amino acid glutamine prompted us to investigate substitute compounds appropriate for culture conditions. The effect of two glutamine-containing dipeptides, alanylglutamine (Ala-Gln) and glycylglutamine (Gly-Gln), on the growth behavior of a hematopoietic cell line in culture (K562) was investigated. Growth rates and [3H]thymidine incorporation rates of cells cultivated in sterile-filtrated media, containing glutamine (Gln) or Ala-Gln or Gly-Gln, were not statistically different. Although heart-sterilization of media containing Gln caused approximately 95% decomposition of the Gln, both dipeptides remained unaltered. Consequently, cell growth was drastically decreased when autoclaved free Gln-containing media were used, but growth was unaffected in the presence of autoclaved dipeptides. Both Ala-Gln and Gly-Gln have an advantage over free Gln as growth factors for cell culture due to the stability of the dipeptides during both autoclaving and storage; the biological activity, however, is comparable.

Cell Division↗
PubMed1988

Alanylglutamine reduces muscle loss of alanine and glutamine in post-operative anaesthetized dogs.

1. The present study examined the effect of an infusion of the dipeptide alanylglutamine or of the corresponding amino acids alanine and glutamine in equimolar amounts (10 mumol min-1 kg-1) on the canine hindlimb exchange of alanine and glutamine in the post-operative anaesthetized dog. In contrast to glutamine, the dipeptide alanylglutamine is stable in aqueous solution and therefore would be a suitable substrate for parenteral nutrition. 2. The infusion of alanylglutamine increased (a) the arterial concentration of alanylglutamine to a plateau level (120 +/- 9.5 mumol/l, mean +/- SEM) 20 min after start of the infusion, (b) the mean arterial alanine concentration from 761 +/- 42 to a plateau of 1500-1700 mumol/l (P greater than 0.01) and (c) the arterial glutamine concentration from 407 +/- 51 to a plateau of 1050-1500 mumol/l (P greater than 0.01). Alanine and glutamine levels were slightly higher (14% and 26%, respectively, NS) in the group receiving the equimolar amount of alanine and glutamine. 3. Infusion of alanylglutamine for 1 h abolished the net efflux of glutamine (from -0.80 +/- 0.1 to -0.03 +/- 0.2 mumol min-1 kg-1; P greater than 0.05) and invoked a net influx of alanine (from -0.50 +/- 0.19 to +0.27 +/- 0.14 mumol min-1 kg-1; P greater than 0.01). These changes were similar to those achieved when the two amino acids were infused. 4. This study demonstrates that during short-term administration of alanylglutamine or of the corresponding amino acids the nitrogen release from the hindlimb of the anaesthetized post-operative dog via alanine and glutamine is reduced.

Alanine↗
PubMed1988

Asparaginase-induced derangements of glutamine metabolism: the pathogenetic basis for some drug-related side-effects.

Several side-effects of asparaginase therapy have been said to be a consequence of the glutaminase activity of Escherichia coli asparaginase, especially the deleterious influence on the liver function. We report here the drug-induced impairments of asparagine and glutamine metabolism in correlation to concentrations changes of plasma proteins, synthesized in the liver, in patients with acute lymphatic leukaemia. One hour after asparaginase application, plasma glutamine decreased to 5% (0-39%: median, range) of the initial values, with a subsequent rise to concentrations slightly lower than those prior to therapy. During the 14 days of drug application the fasting plasma concentrations of glutamine fell to a median of 63% of the pre-therapeutic levels, indicating a depletion of the glutamine pools. Two days after the end of asparaginase application, in one patient the glutamine concentrations increased to the pre-therapeutic range. Plasma concentrations of fibrinogen and antithrombin III decreased to 46% and 56%, respectively, of the initial values, with a slight increase 2 days after the end of therapy. The changes of plasma protein concentrations followed the course of plasma glutamine and asparagine. From that we deduce that the hepatic synthesis of the plasma proteins might be influenced by asparagine and glutamine depletion as a consequence of the therapy with E. coli asparaginase.

Amino Acids↗
PubMed1988

Influence of leupeptin on protein and amino-acid metabolism in septic rats.

We investigated the influence of leupeptin (LP) intraperitoneal injection (40 mumol/2 days) on protein and amino-acid metabolism of septic rats (cecal ligation). All septic rats lost weight (-17 +/- 4 g), which was not prevented by LP administration (-24 +/- 1.8 g, n.s.). LP injection evoked weight loss even in normal rats (p less than 0.05 vs controls). Weight loss was accompanied by enhanced urinary nitrogen losses in all three groups. LP reduced food intake for 47% in control rats. Cecal ligation, and also the administration of LP, led to alterations of amino-acid metabolism. The most important changes were found in muscle free amino-acid concentrations with highly decreased levels of free glutamine. A glutamine deficiency is known to be related to a decreased rate of protein synthesis. The proteolytic rate in incubated soleus muscle was increased for 11.5% and even higher in LP-treated septic rats (+22%). It is concluded that the administration of LP cannot reverse protein catabolism in sepsis--possibly because LP does not influence those enzymes or proteases involved in tissue loss, or LP is inactivated by enzymes in rat tissues.

Amino Acids↗