[Age-related changes in the blood-brain barrier in the rat with reference to methionine, lysine, glutamic acid and N-methyl-N-nitrosourea]. / Altersveränderungen der Blut-Hirn-Schranke bei der Ratte in bezug auf Methionin, Lysin, Glutaminsäure und N-Methyl-N-nitrosoharnstoff.

One possible cause of the decline in brain function with aging might be an age-related change in the blood-brain barrier (BBB). Therefore, we assessed the "Brain Uptake Index" (BUI) by the method of Oldendorf (1970) in 99 male Sprague-Dawley rats aged 3-4 months (young), 7-11 months (adult) and 28-31 months (old) for the following compounds: methionine, lysine, glutamic acid and N-methyl-N-nitrosourea (MNU). The BUIs of methionine and MNU showed marked but contrasting biphasic changes with age: the adult animals had the highest BUIs for methionine and the lowest for MNU, compared with the young and old groups. With lysine, a declining tendency with age was indicated, whereas no differences could be detected with glutamic acid. The results suggest that the BBB undergoes different changes in development and aging, leading to an optimal amino acid transport and minimum penetration of lipophilic agents (MNU) in the adult brain. Thereafter, the opposite takes place, reducing necessary transport and increasing the penetration of lipophilic compounds.

[Pharmacokinetics of nitrosomethylurea in oncologic patients]. / Farmakokinetika nitrozometilmocheviny u onkologicheskikh bol'nykh.

Kinetics of blood-nitrosomethylurea (NMU) was studied in 68 patients with lung cancer, malignant melanoma and lymphoma who had received NMU-based combination chemotherapy. The results were used for computing main pharmacokinetic parameters such as logarithm of calculated initial concentration, time of half-elimination from blood, area under the kinetic curve of concentration, volume of distribution in the body and clearance. All those values were shown to significantly differ with individual patients. A longer retention of the drug in blood flow (as evidenced by increased time of half-elimination and area under kinetic curve matched by decreased volume of distribution and clearance) was registered in responders than in non-responders, the difference sometimes reaching statistical significance.

[Studies of the target cell problem in N-nitroso-N-methylurea induced leukemogenesis]. / Untersuchungen zur Targetzell-Problematik bei der durch N-Nitroso-N-methylharnstoff induzierten Leukämogenese.

After i.p. application of 14C-nitrosomethylurea (NMU), mice were killed at different periods and the 14C-activity in various organs was determined by scintillation counting and by autoradiography. Contrary to expectations, bone marrow showed a significantly higher activity than the thymus, which is the supposed target-organ for the lymphatic leukemogenesis. The specificity was secured by examinations of the proliferation kinetics. The radioautographic results of bone marrow favorize the lymphatic cells as the target for NMU. The target-cell problem is discussed in respect to thymectomy examinations and recent results on nude mice. With high probability the thymus is not essential for lymphatic leukemogenesis.