The dynamics of concentration of the main fluorescent component of Ukrain in the tissues and blood plasma of rats with W-256 tumor after a single intravenous injection.

We determined the blood plasma and tissue concentrations of the main fluorescent component of free Ukrain after a single intravenous injection of this substance (0.25 mg/kg) to intact and carcinosarcoma W-256 bearing rats using ion-pair high-performance liquid chromatography with fluorescent detection. The plasma and tissue concentrations of Ukrain were lower than expected, assuming its uniform tissue distribution and first-order kinetics. W-256 tumor tissue was the only tissue that showed accumulation of Ukrain (its concentration at 45 min after injection was up to 2.84-fold higher than in the blood plasma). Based on the elevation of Ukrain concentration in tissues at approximately 15 min after injection and taking into account its high molecular weight as well as the high dimensions of the Ukrain molecule or ion at physiological pH values, we conclude that the preparation penetrates into tissues by active transport or by favored diffusion. Due to the existence of such transport systems together with excretion of Ukrain and probably also its biotransformation, the disappearance of the preparation from the blood cannot be described using a one-compartment model. A relatively higher affinity for Ukrain was observed in tumor tissue and liver, while affinity was lowest in the brain and muscles. The presence of tumors decreased Ukrain concentrations in plasma and normal tissues in comparison with those in control animals.

Results of Ukrain monotherapy of prostate cancer.

This study included 15 patients with newly diagnosed prostate cancer with an average age of 71 years (62-85 years). The patients received Ukrain at a total dose of 100 mg (10 mg intravenously every second day, 10 injections altogether). After two to three injections of Ukrain, all the patients noted considerable subjective improvements in their state. Ukrain increased the amount of total T-lymphocytes, including "active" T-lymphocytes, decreased the content of T-suppressors and increased that of T helpers, correspondingly raising the T helper/T-suppressor ratio. Our results undoubtedly indicate the efficacy of Ukrain in the treatment of prostate cancer.

Influence of Ukrain on DNA, RNA and protein synthesis in malignant cells.

3H labelled thymidine, uridine and leucine were used to evaluate the synthesis of DNA, RNA and proteins in malignant cells and normal cells incubated with Ukrain in different concentrations. Compared with the controls, the inhibiting effects of Ukrain are demonstrated in guinea pig hepatocytes, CIL hepatocytes, human tonsil cells, two murine lymphomas, murine myeloma, Yoshida cells, two HeLa strains, EsB- and EB- (murine) lymphomas. YAC-1, P815 and human WiDr cells. Ukrain inhibits the DNA, RNA and protein synthesis in malignant cell lines at relatively high concentrations and to a small extent in normal cells.

Influence of Ukrain on human xenografts in vitro.

Tumour cells were taken from human tumour xenografts (HTX) and serially transplanted into nude mice. These cells were used in a colony-forming assay in vitro. Tumour cells were incubated continuously for at least one week with several concentrations of the drug Ukrain. This was done with six different types and the colony formation was scored for each tumour. The drug effects were reported as percent T/C (Test/Control) for the numbers of colonies formed. Activity is considered to be present at T/C < 30%. A clear dose-response effect was found for Ukrain.

Reversed-phase liquid chromatography of alkaloids: Masking effects of inorganic salts.

The addition of salts (investigated cations Na(+), NH(+)(4), K(+), KBu(+)(4) combined with the anions acetate, Br(-), SCN(-) and I(-)) can be used to eliminate peak tailing and to decrease retention of cationic species in the course of the separation of alkaloids from Chelidonium majus L. by reversed-phase chromatography on a ODS Hypersil column, using water-acetonitrile-methanol mixture as eluent. These findings are interpreted in terms of a silanol masking effect. The extended donor-acceptor concept is used to interpret the effectiveness of different salts in masking the active sites of the stationary phase.

Effect of three months treatment with Ukrain on peripheral blood morphology in rodents.

Studies on Albino Swiss mice and Wistar rats have demonstrated that Ukrain administered intraperitoneally (i.p.) for three months produces the following effects in the haematologic parameters: increased leucocytes and decreased thrombocytes. The haemoglobin and erythrocyte levels, as well as haematocrit value, were unchanged. In the leucogram changes were observed; i.e., a fall in the number of neutrophil segments and an increase in the lymphocyte count. The erythrocyte indices, P.C.V., M.C.V., M.C.H. and M.C.H.C. were not changed by a period of three months i.p. Ukrain administration. The observed changes were more marked in female than in male animals and were greater in mice than in rats.

Evaluation of thiophosphoric acid alkaloid derivatives from Chelidonium majus L. ("Ukrain") as an immunostimulant in patients with various carcinomas.

This paper summarizes the preliminary results of two independent clinical trials conducted with the preparation "Ukrain", containing thiophosphoric acid alkaloid derivatives from the plant Chelidonium majus L. (greater celandine), in order to investigate whether it has immunopotentiating properties in cancer patients. A total of twenty-seven patients with various malignancies were treated with "Ukrain" given intravenously in a dose of 10 mg every three days. In all patients the cellular and humoral immune response was studied. There was an increase in both total T-cells and T-helper lymphocytes, a decrease in T-suppressor cells, and normalization of the helper/suppressor (HIS) ratio. A significant increase in erythrocyte-rosette-forming T-cells and NK cells was also demonstrated. Serum immunoglobulin levels, complement components (C3 and C4), and acute phase proteins were not significantly enhanced. Restoration of cellular immunity was accompanied by an improvement in the patients' performance status and in the clinical course of the disease. The treatment was generally well tolerated. The present study shows that some therapeutic benefit from the use of Chelidonium majus ("Ukrain") as an immunostimulant in cancer patients can be achieved.