A method for determination of Ukrain in blood plasma for monitoring and pharmacokinetic study.

We developed a method using high-performance liquid chromatography for the determination of the main fluorescent component of Ukrain, a novel antitumor and immune-stimulating drug. Our method was based on ion-pair separation of Ukrain from perchloric acid extracts using reversed-phase column, buffer with high molarity (0.5 M potassium phosphate, pH 2.65), high concentration of ion-pair reagent in the mobile phase (10 mM octylsulfonic acid), controlled temperature of the separation (45 degrees C) and detection by fluorescence (360/455 nm). Under the above conditions a peak of the main Ukrain compound was resolved from fluorescent peaks of the sum of alkaloids of Chelidonium majus L. although several peaks of alkaloids were retained in Ukrain as traces. The height of this main peak was nearly constant, while the alkaloid peaks varied depending on the series of the preparation; chelidonine and thio-triethylenephosphoramide gave no peaks. Analytical recovery for Ukrain from human plasma was 98.0 +/- 4.5%. Therefore, Ukrain possesses neither significant stable binding to plasma proteins nor adsorption in blood cells.

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.

Comparison of the efficacy of different doses of Ukrain in the combined treatment of breast cancer.

The aim of this study was to compare the efficacy of different Ukrain doses in the combined treatment of 75 patients with breast cancer. The patients were divided into three groups: groups I and II (25 patients each) were treated with 50 mg and 100 mg of Ukrain, respectively, before surgery; group III (25 patients) served as control (without Ukrain treatment). Clinical observations, biochemical, hormonal and immunologic indices indicated that both doses of Ukrain had a similar beneficial effect on patient outcome and may be indicated in the presurgical treatment of patients with breast cancer.

Ukrain: a novel antitumor drug.

A review of the recent literature on the new anticancer drug Ukrain is provided herein. We review Ukrain, a thiophosphate derivative of alkaloids from Chelidonium majus L., its capacity to exert selective cytotoxic and cytostatic effects on tumor cells, simultaneously acting as an immune response modifier, its good tolerance and lack of side effects even after long-term application, perspectives of the application of this drug in oncology.

Brain GABA metabolism after chronic ethanol consumption and withdrawal in rats.

We have studied the activities of the GABA metabolizing enzymes-GABA aminotransferase (GABA-AT), succinic semialdehyde dehydrogenase (SSA-DH) and SSA reductase (SSA-R) and the levels of GABA, glutamine and glutamate in rats preferring water (WP) or ethanol (EP) after 6 months of ethanol consumption and 12 hours to 7 days after withdrawal. We showed decreased GABA levels in the brain stem, decreased GABA-AT activity in the hemispheres and brain stem, and enhanced GABA-AT activity in the striatum of EP rats compared with the control or WP animals following chronic consumption of ethanol. We found decreased activity of SSA-R and SSA-DH in the hemispheres and brain stems of alcohol-treated rats compared to the control rats. Withdrawal (0.5-7 days) induced numerous profound changes in GABA metabolism.

Amino acids and their derivatives in blood plasma of patients with breast cancer treated with Ukrain. Part V.

The present study was undertaken to evaluate the influence of Ukrain on the free amino acids pool in blood plasma in ten patients with breast cancer, treated in the preoperative phase with the drug. The control group consisted of five patients of similar age and advancement of the disease, who did not receive Ukrain before mastectomy. The data obtained from these studies indicate that Ukrain positively influences the metabolism of amino acids and their derivatives. The most characteristic changes were increase of proline, taurine and glutamic acid.

Amino acids and their derivatives in tumour tissue from patients with breast cancer treated with Ukrain. Part VI.

The present study was undertaken to evaluate the influence of Ukrain on the amino acids pool and their derivatives in tumour tissue of ten patients with breast cancer, treated in the preoperative phase with Ukrain. The control group consisted of five patients of similar age and advancement of the disease, who did not receive Ukrain. The data obtained indicate that Ukrain influences cancerous tissue, as demonstrated at the level of amino acids. The most characteristic changes observed in cancerous tissue after treatment with Ukrain were increases in the levels of proline, taurine and glutamic acid.