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PubMed1998

Six-week treatment with Ukrain in rabbits. Part III: Serum levels of thyroid hormones.

The influence of 6-week treatment with Ukrain at doses of 0.3, 1.5 and 3.0 mg/kg i.v. on serum levels of thyroid hormones, i.e., thyroxine and triiodothyronine, was studied in rabbits of both sexes. Ukrain affected the serum levels of both hormones in males. An increase in the thyroxine level was found after Ukrain used at a dose of 1.5 and 3.0 mg/kg i.v., whereas increased triiodothyronine was noted when Ukrain was given at all studied doses. In females the thyroxine level was not altered by Ukrain administration, whereas the triiodothyronine concentration was increased following Ukrain at 0.3, 1.5 and 3.0 mg/kg i.v. it is probable the altered thyroid hormone levels as a result of Ukrain application may contribute to the drug's potent immunomodulatory action.

Adjuvants, Immunologic↗
PubMed1998

A comparative evaluation of the influence of the complex drug Ukrain and its components on the effects of radiation.

The development of cancer therapy is associated with an increased application of therapeutic schedules that combine radiation and different drugs. Ukrain is a promising drug proved to be efficient in the treatment of different tumors when used either before, during or after radiation therapy. Therefore, the issue of the influence of this drug on the effects of radiation is of interest. In previous studies, the ability of Ukrain to ameliorate the harmful consequences of irradiation was demonstrated. Ukrain is a semi-synthetic thiophosphoric derivative of Chelidonium majus L. alkaloids, i.e., it is a complex preparation. Therefore, it is necessary to elucidate which of its components are the active agents that mediate its antiradiation effects. The aim of this study was to compare the radioprotective effects of Ukrain and its components in experiments with animals irradiated by doses within a broad range (from LD50/30 to LD100/30). A total of 1,240 outbred male white mice were gamma-irradiated with an IGUR apparatus using 137Cs as the radiation source. Doses applied ranged from 5.25-7.5 Gy with a 0.75 increment between dosages. Dose rate was 1.41 Gy/min. The experiments have shown that the radioprotective effects of Ukrain are far superior to all its components taken separately, both measured by survival of mice irradiated by different doses, and by the protection coefficient a. These observations suggest that the influence of Ukrain on radiation effects does not result from the antiradiation properties of its components but rather from the concerted action of the specific combination found in Ukrain.

Alkaloids↗
PubMed2000

Comparative evaluation of blood plasma and tumor tissue amino acid pool in radiation or neoadjuvant preoperative therapies of breast cancer with the antitumor drug Ukrain.

This study comparatively evaluated free amino acid pool formation in patients with T1-3N0-2M0 breast cancer treated with the drug Ukrain (25 patients, i.v. 100 mg/course) in combination with preoperative radiation or neoadjuvant therapies (25 subjects, total dose 20 Gy). All the patients underwent radical mastectomy. Preoperative radiation did not essentially change the range of the blood plasma parameters studied. However, we observed decreased concentrations of blood plasma ornithine and citrulline and a reduced content of aminobutyric acid, as compared with levels on admission, which may indicate an acceleration of detoxication processes in the liver. In comparison with healthy mammary gland tissue, the tumor tissue of the patients subjected to radiation therapy showed 1.5- to twofold increased concentrations of cysteate, taurine, aspartate, glutamate, proline, glycine, alanine, valine, tyrosine and histidine, which substantiates the idea of tumor tissue being a trap for numerous energy and plastic substrates and indicates active transport of the above compounds into the tumor. The application of Ukrain had virtually no influence on concentrations of the majority of blood plasma amino acids and derivatives: the total concentration of the compounds studied as well as the essential and nonessential amino acid pools remained unchanged. As compared with healthy breast tissue, the considerably increased levels of thiol-containing amino acids, such as methionine, cystine, cysteate and taurine, in the tumor tissue of patients receiving neoadjuvant therapy with Ukrain, indicates high activity of trans-sulfuration processes in this tissue. Simultaneously, in contrast to radiation therapy, Ukrain induced a marked dose-dependent increase in the concentration of proline in breast tumor tissue. The above changes were consistent with the results of the morphological study which confirmed the emergence of numerous foci of necrosis in the tumor and indicated activation of Ukrain-induced proteolytic and degradation processes in the tumor. The results obtained have led us to conclude that a mechanism of Ukrain's cancerostatic effect is to control the transport and reactions of intermediate amino acid metabolism as well as to activate proline biosynthesis in the tumor, causing enhanced development of connective tissue. It is suggested that an important practical conclusion from the present study is the lack of damaging effect of preoperative radiation therapy in the above regimen and the favorable (normalizing) action of Ukrain, at a course dose of 100 mg, on the amino acid pool formation in the organism of patients with breast cancer.

Adult↗
PubMed1996

Mitogenic properties of Ukrain (NSC-6315170) on human peripheral blood monocytes: clinical implications.

Using a cell-proliferation assay, the authors examined and compared the mitogenic effects of Ukrain and phytohaemagglutinin (PHA) on human peripheral blood mononuclear cells (PBMCs), as well as their synergic effects. It was found that even a short period of pretreatment of the cell with Ukrain had a potent synergic effect on PHA mitogenesis resulting in significantly higher cell stimulation indices than those of PHA alone. Moreover, it was found that a short period of PHA treatment of the cells is almost imperative for Ukrain to exert its mitogenic effects. The mitogenic effect of Ukrain on human PBMCs is consistent with a previous clinical report which found that circulating lymphocytes were significantly increased in cancer patients treated with Ukrain. Thus the in vitro assay used in these studies may serve as a prognostic assay for potential patient responsiveness to Ukrain treatment, as well as a clinical parameter during Ukrain therapy.

Alkaloids↗
PubMed1999

Suicidal behavior in the Ukraine, 1988-1998.

This report studies the available data concerning suicide rates in the Ukraine and points to the importance of appropriate monitoring of suicides and attempted suicides. It illustrates the necessity of collecting this information and of developing "The Ukrainian National Program on Suicide Prevention." Unfortunately, suicide research and publications about suicide rates were prohibited in the former Soviet Union, so some of the data about suicidal behavior in the Ukraine is incomplete. We used the official suicide death statistics of the Ukraine from the Center of Statistics (Ukrainian Ministry of Health) for the period 1988-1998. The overall rate of suicide in the Ukraine is relatively high. Official statistics in the Ukraine show that there were 29.6 suicides per 100,000 population in 1998. The frequency of completed suicide differs in the various regions of the country, suicides being more frequent in the industrially developed regions and in the rural areas of the country than in the cities. In the western part of the Ukraine the frequency of suicide is relatively low (11.1 per 100,000). Between 1988 and 1997 the suicide rate increased by 57%. In 1998 the suicide rate for women was approximately five times lower than that for men.

Adolescent↗
PubMed1998

Ukrain (NSC-631570) in experimental and clinical studies: a review.

The need to find a safe and highly effective cure for neoplastic disease remains a major challenge for modern pharmacology. This paper reviews the available literature on Ukrain (NSC631570), a novel semisynthetic drug obtained from Chelidonium majus L. alkaloids. Ukrain has been demonstrated to possess antineoplastic and immunomodulatory properties. Inhibition of the growth of cancer cell lines in vitro, tumor mass reductions in vivo, and partial and complete remissions in oncological patients, occur as a result of Ukrain application. The drug may interfere directly with the metabolism of cancer cells and it also improves the functioning of the host immune system. Diminished synthesis of DNA, RNA and proteins, the inhibition of cellular oxygen consumption, and the induction of programmed cell death in malignant cells have been described following Ukrain administration. The drug can also modify the immunological response via an increase in the number of total T-cells and a normalization of the T-helper/T-suppressor lymphocyte ratio. Ukrain therapy produces neither toxic consequences nor allergic reactions towards the drug. Several case reports and clinical trial data indicate that Ukrain may ameliorate effectively the progress of neoplastic disease and/or induce a total cure.

Adjuvants, Immunologic↗
PubMed1998

Study of the antitumor effect of Ukrain: the role of macrophage secretion of alpha-1-proteinase inhibitor.

The positive antitumor effect of Ukrain was shown following i.m. injection of a mixture of this drug with Krebs-2 carcinoma cells to CBA mice. The protective effect was suggested to be a result of the influx of macrophages into the site of Ukrain injection. In contrast, contralateral administration of Ukrain had a negative effect, confirming our hypothesis that Ukrain attracts cytolytic macrophages. In the murine HA-1 hepatoma model treated by single or repeated Ukrain injections, a moderate positive effect of Ukrain was related to increased macrophage (alpha-1-proteinase inhibitor (PI) secretion. The role of tumor cells and macrophages in the secretion of PI (the main inhibitor of serine proteinases) during tumor development is discussed.

Alkaloids↗
PubMed2000

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.

Algorithms↗
PubMed1992

Some pharmacological properties of prolonged administration of Ukrain in rodents.

Some pharmacological properties of Ukrain administered intraperitoneally (i.p.) once daily for three months in mice and rats of both sexes were studied. A three month treatment with Ukrain significantly depressed the spontaneous locomotor activity and did not affect the motor coordination of mice and rats of both sexes. Ukrain did not affect the body weight gain as well as the mass of internal organs; the exception was an increase in the mass of the spleen in rats. Biochemical studies indicated that a three month treatment with Ukrain depressed the whole brain dopamine (DA) concentrations and did not affect the noradrenaline (NA) concentrations. Long-term administration of Ukrain showed no characteristic changes in the concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the whole brain. The observed changes after three months' treatment with Ukrain are similar in mice and rats of both sexes.

Alkaloids↗
PubMed1992

The immunomodulating preparation Ukrain does not induce anaphylactic sensitization in mice and guinea pigs.

The ability of Chelidonium majus L. alkaloids derivative Ukrain to induce an anaphylactic sensitization was tested on mice and guinea pigs. The levels of IgE antibody in the mouse sera, and IgG1a, IgG1b as well as IgE antibody levels in guinea pig sera, were evaluated by passive cutaneous anaphylaxis (PCA) tests. Ukrain alone or adsorbed on aluminium hydroxide gel (alum) introduced into BALB/c mice in several subcutaneous injections was unable to stimulate measurable anti-Ukrain IgE antibody response. Moreover, Ukrain introduced together with ovalbumin (OA) into mice in the course of immunization with OA induced lower anti-OA antibody response as compared to the response induced by OA alone. Ukrain adsorbed on alum and injected subcutaneously into guinea pigs did not induce measurable IgG1a, IgG1b and IgE antibody response. The present results suggest that the immunomodulating preparation Ukrain could be therapeutically safe at least as far its inability to induce anaphylaxis is concerned.

Adjuvants, Immunologic↗
PubMed1996

Comparison of chemotherapy and X-ray therapy with Ukrain monotherapy for colorectal cancer.

Ninety six colorectal carcinoma patients were included in a randomised study, 48 were treated with Ukrain monotherapy (15 with metastatic and 33 with nonmetastatic colorectal carcinoma) and 48 with 5-fluorouracil (5-FU) and X-ray therapy (the same randomised groups). The results of therapy including clinical, haematological, immunological and biochemical parameters show that Ukrain has favourable properties in the treatment of colon and rectal cancer as a monotherapy because of its malignotoxic and immunomodulating action. Objective response rate in the group of metastatic colorectal cancer treated by Ukrain was 40%. There was no registered tumour regression in the group treated by 5-FU. Operability is strongly facilitated by pretreatment with Ukrain. The survival rate (up to 21 months) in the Ukrain-treated patients with nonmetastatic colorectal cancer was 78.6% and 33.3% in a corresponding control group. Ukrain is a new effective drug in the therapy of colorectal cancer. It can be useful both for the therapy of metastatic colorectal cancer and for neoadjuvant therapy of nonmetastatic colorectal cancer.

Alkaloids↗
PubMed1996

Influence of Ukrain on the redox processes of hepatocytes.

In our in-vitro experiments on the addition of Ukrain into an incubation solution of intact rat liver-cell homogenate, it was indicated that the effect of Ukrain depends on the metabolic redox chain. The endogenous respiration rate which is supported by ionic solution of incubation only, with Ukrain addition submits to a 25% decline. At the same time Ukrain stimulates NADP-dependent oxidation. Since the oxygen consumption increase under Ukrain's influence is characteristic of the metabolic state 4 of Chance (1956), it could be explained as a protonophoric effect (6). The data obtained indicate a complex mechanism of Ukrain's influence on the processes basic for the living organism, the breakage of which always leads to the pathological changes.

Alkaloids↗
PubMed2002

Using the Nordic-Baltic perinatal death classification to assess perinatal care in Ukraine.

OBJECTIVE: To identify health care issues important to reduce the perinatal mortality rate (PMR) in Ukraine. STUDY DESIGN: Perinatal deaths in the Donetsk region (Ukraine) in 1997-1998 were compared with those in Denmark in 1996 by using the Nordic-Baltic classification for perinatal deaths. Clinical guidelines, use of technology and rates of interventions in the two regions were described. RESULTS: A two-fold increase in PMR was found in Ukraine compared to Denmark, mainly explained by higher rates of antenatal deaths of growth restricted fetuses, intrapartum deaths, and neonatal deaths due to asphyxia. Vacuum extraction is rarely used in Ukraine. The clinical guidelines for care differ significantly between the two regions. CONCLUSION: Appropriate use of technology and implementation of evidence-based guidelines should be a matter of high priority in the Donetsk region, Ukraine.

Apgar Score↗
PubMed2004

Preterm birth rates in Avon County, England, and urban Ukraine.

OBJECTIVE: We compared rates of total and spontaneous preterm birth in Avon County, England and urban Ukraine to explore whether adverse conditions in the former eastern bloc influenced the preterm rate. STUDY DESIGN: Women who had last menstrual period (LMP) in a specified time window were recruited from geographically defined areas. Data were gathered between 1992 and 1995, using maternal questionnaires and medical record abstraction, with comparable methods in both sites insofar as possible. There were 13731 births in Avon and 3087 in Ukraine. Rates of total and spontaneous preterm births were compared, taking account of maternal characteristics and other relevant variables. RESULTS: The total preterm birth rates were similar (5.9%, Ukraine; 5.5%, Avon) but the spontaneous preterm rate was about 60% higher in Ukraine (5.0% versus 3.1%). Maternal characteristics and measurement differences did not explain the discrepancy. CONCLUSION: The difference in the spontaneous preterm rates may reflect differences in obstetrical management resulting from shortages of medical supplies and equipment in Ukraine.

Adolescent↗
PubMed1992

Activation of spleen cell lytic activity by the alkaloid thiophosphoric acid derivative: Ukrain.

Ukrain is a semisynthetic compound consisting of alkaloids from Chelidonium majus L. conjugated to thiophosphoric acid, with immunomodulatory and therapeutic properties in cancer patients. The present in vitro studies demonstrate that Ukrain is an effective biological response modifier in that it augmented, by up to 48-fold, the lytic activity of spleen lymphocytes obtained from alloimmunized mice. The lytic activities of IL-2-treated spleen cells and peritoneal exudate lymphocytes were also increased significantly by the addition of Ukrain to the CML assay medium. The highest Ukrain-induced enhancement of spleen lymphocyte lytic activity in vitro was found to occur at 18 days after alloimmunization, was dose dependent and specific for the immunizing P815 tumor cells. Since Ukrain was present only during the CML assays, its mode of action is thought to be via direct activation of the effector cell's lytic mechanism(s).

Alkaloids↗
PubMed1998

Macrophage stimulation and antitumor effect of Ukrain.

It has previously been demonstrated that Ukrain administration (0.5 mg in mice of 20 g, five times) to A/Sn mice results in retardation of HA-1 tumor growth in the liver and a prolongation of lifespan compared with untreated controls. In the present study Ukrain was tested as a macrophage stimulator in intact mice and animals with HA-1 hepatoma. There were no changes to the carbon particles phagocytosis rate in the case of a single administration of Ukrain to intact mice. Significant secretion of procathepsin B into ascitic fluid was shown in tumor mice as well as marker enzyme of macrophages beta-hexosaminidase activity, suggesting an influx of macrophages into ascites. Single Ukrain administration increased this index, and repeated drug injections were followed by a tendency to normalization of secretion. The cytolytic effect of Ukrain against tumor cells (as a result of macrophage stimulation) is the most probable mechanism of its antitumor action, but this suggestion needs further experimental evidence with special attention paid to the balance of proteinases and endogenous proteinase inhibitors.

Adjuvants, Immunologic↗
PubMed1998

The influence of Ukrain on the growth of HA-1 tumor in mice: the role of cysteine proteinases as markers of tumor malignancy.

The influence of Ukrain (exerting a malignotoxic effect in vivo according to Nowicky J.W. et al [1]) on the growth of Hepatoma A (HA-1) tumors in mice and cysteine proteinases as markers of tumor growth and malignancy was studied. Ukrain administration (0.5 mg per mice of 20 g, in each of 5 i.p. injections) resulted in a reproducible and significant retardation of HA-1 tumor growth in the liver and a prolongation of lifespan compared with the untreated control. Repeated Ukrain administration to mice increased the number of macrophages in ascites, decreased the number of tumor cells, and concomitantly reduced the increased level of monocytes in peripheral blood. In ascitic cells the specific activity of cathepsin B was higher than in the intact liver and was not influenced by Ukrain; activity of cysteine proteinases studied in ascitic fluid was much higher than that in serum. Tumor growth was followed by a decrease in cathepsin B activity in the liver and serum at day 10. Ukrain administration has a tendency to normalize the disturbances of cathepsin B activity during tumor development. The cathepsin L activity changes in ascitic fluid were more impressive than those of cathepsin B, indicating the special role of this cysteine proteinase in HA-1 tumor growth and invasiveness. The role of cysteine proteinases as markers of tumor malignancy and invasiveness is discussed.

Alkaloids↗
PubMed2000

Bcl-2 overexpression protects human keratinocyte cells from Ukrain-induced apoptosis but not from G2/M arrest.

Exposure of ME180 and A431 carcinoma cells to Ukrain (NSC-631570), a semisynthetic compound consisting of alkaloids isolated from Chelidonium majus L. (Papaveracea), results in cell cycle arrest at the G2/M phase. Ukrain selectively inhibits growth of ME180 and A431 cells at a concentration range from 3.5 microM to 7.0 microM and induces apoptosis. In contrast, normal human keratinocytes showed no difference in the kinetics of progression through the cell cycle in response to this compound. We found that at a concentration of 7.0 microM of this drug Bcl-2 protein overexpression protected HaCaT cell line keratinocytes against apoptosis induced by Ukrain but did not prevent G2/M arrest. Following exposure of normal keratinocytes to Ukrain, we detected an increase in Bcl-2 protein levels and a significant change in protein modification as suggested by observation of its different isoform with shifted electrophoretic mobility. Bcl-2 protein expression and its isoform distribution did not change substantially in ME180 and A431 carcinoma cells. We also suggest that drug-induced mitotic arrest and apoptosis represent dual Ukrain action on cell cycle progression machinery and Bcl-2-involved program cell death in the cell.

Alkaloids↗