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PubMed2000

New biochemical mechanisms of the anticancer effect of Ukrain in the treatment of cancer of the urinary bladder.

The aim of this study was to elucidate the mechanisms of the anticancer effect of Ukrain by comparing the processes of formation of the pool of free amino acids and their derivatives in the blood plasma and tumor biopsy specimens and unchanged bladder tissue in 28 patients with T1N0M0 bladder cancer. The examination was carried out before and after Ukrain treatment (10 mg i.v./day, for 20 days), which was combined with systemic chemotherapy for bladder cancer. Twenty-eight patients served as controls and received systemic chemotherapy only. Compared with healthy donors, the blood plasma of patients with urinary bladder cancer showed decreased concentrations of thiol-containing free amino acids and glutamine (Gln) and increased levels of nonessential (glutamic acid, proline, alanine) and aromatic (phenylalanine) free amino acids. In contrast to conventional chemotherapy, treatment with Ukrain eliminated the blood plasma amino acid imbalance in patients with bladder cancer, concomitantly enriching the pool of free amino acids and their derivatives in unchanged urinary bladder tissue and decreasing concentrations of Gln and leucine (Leu), regulators of malignant cell proliferation and differentiation, by 30-50%. In this situation, the concentrations of Gln and Leu in tumor tissue and the surrounding healthy urinary bladder tissue correlated highly significantly and negatively (r = -0.95). In conclusion, Ukrain prevents active free amino acid transport into urinary bladder tumor tissue, inhibiting the activities of protein biosynthesis, gluconeogenesis and energy production. The combined decrease in Gln and Leu levels in urinary bladder tumor tissue is a specific sign of the antitumor effect of Ukrain and a mechanism of its cancerostatic action by controlling the processes of amino acid pool formation in the tumor.

Alkaloids↗
PubMed2000

Effects of Ukrain on the activities of DNA-nicking enzymes.

We studied the effects of Ukrain, a novel antitumor drug, on the activities of calcium, magnesium-dependent endonuclease (CME) and manganese-dependent endonuclease (MnDE) in rat liver nuclei, the activity of topoisomerase I assessed by pUC19 plasmid relaxation and CME activity in the nuclei of lymphocytes from colon cancer patients. Ukrain was found to exert a dose-dependent inhibiting effect on both CME and MnDE, similar to that exerted by erythropoietin, which was used as a reference preparation. Both Ukrain and erythropoietin also caused dose-dependent inhibition of topoisomerase I activity. The influence of Ukrain on CME activity in the nuclei of the lymphocytes of colon cancer patients was differential, depending on treatment efficacy. The results suggest that DNA-nicking enzymes may be a target of Ukrain and may mediate its antitumor effects.

Alkaloids↗
PubMed2000

Induction of apoptosis in cultured Chinese hamster ovary cells by Ukrain and its synergistic action with etoposide.

The induction of apoptosis by Ukrain, a novel antitumor drug, was studied in Chinese hamster ovary (CHO) cells bearing multiple copies of recombinant human erythropoietin gene incorporated into their genome (cell lines CHO-k38 and -k38/12). Ukrain was found to be capable of the in vitro induction of apoptosis in the cell lines studied. The effect was less expressed in cells with type I multiple drug resistance (k38/12). Ukrain acted synergistically with etoposide, i.e., the combined effect of both agents was evident at significantly reduced concentrations. This suggests that pharmacological compositions of the drugs may reduce the effective doses used in chemotherapy and thus significantly diminish its toxic side effects. Ukrain was found to exert an unusual effect, manifested as the inhibition of protein secretion by target cells. This phenomenon may be used for the express determination of cell sensitivity to colchicine-like cytostatics, including Ukrain.

Alkaloids↗
PubMed1992

Modification of antinociceptive action of morphine by Ukrain in rodents.

Morphine-induced (0.1 mg/kg s.c.)antinociceptive action was determined in rodents by using the writhing syndrome, hot plate and tail-flick tests. Ukrain given i.p. in doses equivalent to 0.05 and 0.1 LD50 did not affect the reactivity of the mice in the writhing syndrome test. Only in a dose of 0.1 LD50 did Ukrain produce an antinociceptive effect in the hot-plate and tail-flick tests. Ukrain significantly enhanced the antinociceptive effect of morphine in the hot-plate and tail-flick tests. The action of morphine was significantly suppressed by Ukrain in the writhing syndrome test in mice. These results indicated that Ukrain modified the antinociceptive action of morphine.

Acetates↗
PubMed1992

Enhancement of macrophage tumouricidal activity by the alkaloid derivative Ukrain. In vitro and in vivo studies.

Ukrain is a semisynthetic drug with immunomodulatory properties, derived from Chelidonium majus L. alkaloids and thiophosphoric acid. The effect of this compound on the growth of Balb/c syngenic mammary adenocarcinoma was assessed. Intravenous, but not subcutaneous or intraperitoneal, administration of this drug was found to be effective in delaying tumour growth in an actual therapeutic protocol initiated five days after tumour implantation. No untoward side-effects were observed using these in vivo treatment modalities. The role of macrophages in the observed retardation of tumour development was investigated using peritoneal exudate macrophages (PEM) in cytotoxicity assays. In previous studies, the authors have found that PEM of mammary tumour bearing mice lose their capacity to kill a variety of tumour target cells including the in vitro cultured homologous tumour cells (DA-3). Pretreatment of PEM from normal mice with 2.5 microM Ukrain for 24 h followed by stimulation with either IFN-gamma or with LPS+IFN-gamma enhanced their cytotoxic activity. Treatment of PEM from tumour bearing mice with 2.5 microM Ukrain and LPS results in a reversal of their defective cytotoxic response against the DA-3 target cells. Furthermore, Ukrain alone, in the absence of a secondary signal, induced the activation of tumouricidal function of PEM from tumour bearing but not from normal mice. These data indicate that Ukrain's in vivo effects against the development of mammary tumours may be due, at least in part, to its ability to restore macrophage cytolytic function.

Adenocarcinoma↗
PubMed1992

Ukrain both as an anti cancer and immunoregulatory agent.

Thirty six stage III cancer patients were treated with Ukrain, a semisynthetic drug derived from Chelidonium majus L. alkaloids conjugated with thiophosphoric acid. The drug was injected intravenously every second day in a dose of 10 mg per injection. Each patient received 300 mg of the drug (30 injections). The cytostatic effect of Ukrain was monitored clinically and by ultrasonography (USG) and computer tomography (CT), as well as by determination of CEA and CA-125 in the sera of patients with rectal and ovarian cancers, respectively. The influence of Ukrain on immune parameters was evaluated by monoclonal antibodies (MAb) to CD2, CD4, CD8 and CD22. The influence of Ukrain on immune parameters in cancer patients was matched with its effect on these parameters in 20 healthy volunteer controls. The results obtained indicate that Ukrain, in a concentration not cytostatic in normal cells, is cytostatic for malignant ones, and may suppress the growth of cancer. The compound also has immunoregulatory properties, regulating the T lymphocyte subsets.

Adjuvants, Immunologic↗
PubMed2005

Effect of Ukrain on the growth and metastasizing of Lewis carcinoma in C57BL/6 mice.

We studied the effect of the anticancer drug Ukrain on Lewis carcinoma in C57BL/6 mice. A marked progressive anticancer and antimetastatic effect was observed. On day 33 of tumor development, the tumor growth inhibition and metastases inhibition index were 71.5% and 73.1%, respectively. The antimetastatic effect of the drug manifested as a decrease in both number and volume of lung metastases. This finding demonstrates that treatment with Ukrain in Lewis carcinoma-bearing mice not only prevents the formation of new metastases but also inhibits the growth of existing ones. In addition to possessing anticancer and antimetastatic effects, Ukrain has been demonstrated to affect parameters characterizing the state of the immune system. This effect manifested as an increase in the endocrine function of the thymus (a central organ of the immune system), an increase in serum interferon, adhesion of peritoneal macrophages and formation of antibodies against thymus-dependent antigen by spleen plasma cells. Together with intensification of functional activity of the immune system, Ukrain increased the number of lymphoid cells and monocytes in peripheral blood. In addition to the increase in lymphocytes, the number of large granular lymphocytes also increased, i.e., cells possessing natural cytotoxic activity. The results obtained suggest that the antitumor, and especially the antimetastatic, effect of Ukrain is due to its immune-modulating properties, specifically, activation of antitumor resistance concerned with release of interferon and thymus humoral factors. Natural killer (NK) activity is one part of this resistance. NK cells are able to recognize and eliminate from the circulation cells with the potential to form metastases.

Alkaloids↗
PubMed2005

[Effect of alkaloid sanguinarine and a pharmaceutical preparation ukrain on modulation of vesicular membrane fusion and actin cytoskeleton of macrophages].

A study was made of modulations of lysosome-phagosome fusion process and of fibrillar actin content in mouse peritoneal macrophages by an antitumor alkaloid sanguinarine and a derivative drug Ukrain. In addition, effects of these substances on in vitro polymerization of monomeric globular actin from rabbit muscle were investigated. Sanguinarine and Ukrain stimulated lysosome-phagosome fusion and increased the content of polymerized fibrillar form of actin in mouse macrophages. Effects of these substances were enhanced at their higher concentrations. Both sanguinarine and Ukrain induced in vitro polymerization of globular actin from rabbit muscle. A possible role of sanguinarine and Ukrain in changing vesicular membrane states during intracellular membrane interaction in lysosome-phagosome fusion process was discussed. The influence of these substances on actin polymerization and actin cytoskeleton rearrangement was evaluated. It could be supposed that sanguinarine and Ukrain may alter intracellular membrane transport.

Actins↗
PubMed1996

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.

Alkaloids↗
PubMed1996

Action of Ukrain, a cytostatic and immunomodulating drug, on effects of irradiation.

The ability of Ukrain, a cytostatic and immunomodulating semisynthetic compound of thiophosphate-modified alkaloids of Chelidonium majus L., to modify the effects of irradiation was studied in CBA/J mice using the dosage of the drug from 0.2 to 10 mg/kg. Ukrain was found to increase the survival rate of mice by 50-60 percent at irradiation doses from 6.00 to 6.75 Gy with no effect at the dose of 7.5 Gy. Varying the dosage of the drug did not influence the outcome of irradiation under experimental conditions employed. Maximal increase in the survival rate of the mice was noted when the drug was administered within the interval from 6 h before to 3 h after irradiation. It is noteworthy that under no circumstances did the administration of Ukrain result in a decrease in the survival rate of irradiated animals. The main outcome of the present study is the finding that Ukrain is capable of modifying the effects of irradiation when applied in both prophylactic and curative regimens. The effects of Ukrain are evident at doses from 0.2 to 10 mg/kg over the entire time-range studied and under doses of irradiation not exceeding LD 85/30. The drug was also found to be able to modify the effects of prolonged irradiation.

Adjuvants, Immunologic↗
PubMed1996

Effect of six-month treatment with Ukrain on early osteoporosis induced by ovariectomy in rats. Part I: Preliminary studies of bone parameters.

Ukrain, thiophosphoric acid alkaloid derivatives from Chelidonium majus L. was administered intraperitoneally in a dose of 28 mg/kg (equivalent to 0.1 LD50) every other day for six months to female rats with ovariectomy-induced early osteoporosis. Administration of Ukrain was started on the second day after the surgical operation. At the end of the long-term treatment with Ukrain each rat was tested for the strength of both humeri and some parameters of rat femur were measured. The body weight of ovariectomized rats was also examined. The present results show that the decrease in the mechanical strength of the humeral bones and some changes in the femur caused by ovariectomy were prevented by the six-month treatment with Ukrain. However, in both ovariectomized groups and in ovariectomized rats pretreated with Ukrain an increase of body weight was observed.

Alkaloids↗
PubMed1999

Thyroid carcinoma in children and adolescents in Ukraine after the Chernobyl nuclear accident: statistical data and clinicomorphologic characteristics.

BACKGROUND: The increase in the number of childhood thyroid carcinoma cases in Ukraine after the Chernobyl nuclear accident in 1986 prompted the development of a registry of thyroid carcinoma cases at the Institute of Endocrinology and Metabolism in Kiev. In the current study, the authors report the statistical data and clinicomorphologic features of the cases included in this registry. METHODS: To study the incidence, and age and gender distribution of thyroid carcinoma in Ukraine, the authors compiled complete clinical information from cases diagnosed and treated at the Institute of Endocrinology and Metabolism and statistical reports submitted to the registry from 27 regions of Ukraine. Morphologic features of the resected tumors were examined and were included in the database. RESULTS: During the 5 years preceding the Chernobyl nuclear accident, a total of 59 cases of thyroid carcinoma were identified in the birth to 18 years age group (25 in children age < or = 14 years and 34 in adolescents ages 15-18 years). Between 1986 and 1997, the total number of thyroid carcinomas in Ukrainian children and adolescents was 577 (358 children and 219 adolescents). Morphologically, the thyroid tumors overwhelmingly were papillary carcinomas, and the majority of these also showed a follicular and/or solid growth pattern. Lymph node metastases and other extrathyroidal spread were common, thus necessitating total thyroidectomy and lymph node dissections in many patients. CONCLUSIONS: Between 1990 and 1997, a significant increase in the incidence of thyroid carcinoma was noted in children and adolescents in Ukraine; the group most affected was comprised of the individuals who were age < or = 5 years in 1986 (the year of the Chernobyl nuclear accident). The largest number of cases occurred in patients living in areas of thyroid radiation doses of > or =0.50 grays. The morphologic features of those thyroid tumors suggest that they are aggressive tumors with a high frequency of lymph node metastases, venous invasion, and extrathyroidal spread.

Adolescent↗
PubMed2006

Breast cancer in Belarus and Ukraine after the Chernobyl accident.

An increase in breast cancer incidence has been reported in areas of Belarus and Ukraine contaminated by the Chernobyl accident and has become an issue of public concern. The authors carried out an ecological epidemiological study to describe the spatial and temporal trends in breast cancer incidence in the most contaminated regions of Belarus and Ukraine, and to evaluate whether increases seen since 1986 correlate to radiation exposure from the Chernobyl accident. The authors investigated the trends through age-cohort-period-region analyses of district-specific incidence rates of breast cancer for Gomel and Mogilev regions of Belarus and Chernigiv, Kyiv and Zhytomir regions of Ukraine. Dose-response analyses were based on Poisson regression, using average district-specific whole body doses accumulated since the accident from external exposure and ingestion of long-lived radionuclides. The study demonstrated increases in breast cancer incidence in all areas following the Chernobyl accident, reflecting improvements in cancer diagnosis and registration. In addition, a significant 2-fold increase in risk was observed, during the period 1997-2001, in the most contaminated districts (average cumulative dose of 40.0 mSv or more) compared with the least contaminated districts (relative risk [RR] in Belarus 2.24, 95% confidence interval [CI] 1.51-3.32 and in Ukraine 1.78, 95% CI=1.08-2.93). The increase, though based on a relatively small number of cases, appeared approximately 10 years after the accident, was highest among women who were younger at the time of exposure and was observed for both localised and metastatic diseases. It is unlikely that this excess could be entirely due to the increased diagnostic activity in these areas.

Breast Neoplasms↗
PubMed2005

Reconstruction of (131)I radioactive contamination in Ukraine caused by the Chernobyl accident using atmospheric transport modelling.

The evaluation of (131)I air and ground contamination field formation in the territory of Ukraine was made using the model of atmospheric transport LEDI (Lagrangian-Eulerian DIffusion model). The (131)I atmospheric transport over the territory of Ukraine was simulated during the first 12 days after the accident (from 26 April to 7 May 1986) using real aerological information and rain measurement network data. The airborne (131)I concentration and ground deposition fields were calculated as the database for subsequent thyroid dose reconstruction for inhabitants of radioactive contaminated regions. The small-scale deposition field variability is assessed using data of (137)Cs detailed measurements in the territory of Ukraine. The obtained results are compared with available data of radioiodine daily deposition measurements made at the network of meteorological stations in Ukraine and data of the assessments of (131)I soil contamination obtained from the (129)I measurements.

Air Movements↗
PubMed2000

Emergency medicine in Ukraine: challenges in the post-Soviet era.

The practice of emergency medicine in Ukraine is markedly different from the practice in North America. The emergency physician counterpart in Ukraine attends 6 years of medical school then 18 months of prehospital physician training at an EMS base station. Once trained, prehospital physicians work 160 hours/month in 24-hour shifts at the base station as part of a physician-nurse team which answers ambulance requests. Most patients are seen and treated on site of the ambulance call. Patients are transported to the hospital only 20% of the time. Prehospital physicians can expect to earn $35 to $65 per month. Nearly all prehospital physicians are government employees. Since becoming an independent democratic republic, Ukraine's turbulent economy has negatively affected health care. Deaths from infectious diseases, including vaccine-preventable illnesses are 10-fold to that of Western countries. A 90% income tax discourages the private practice of medicine. Medical care is provided free of charge, however, if a patient wants a higher standard of care, they may have to pay an attending physician up to $200. Most medications used to treat emergencies are free, but if thrombolytics are required, the patient will have to pay for them before they are administered. Budgetary constraints limit equipment and technology. The disparity between urban and rural resources is striking as even the most basic equipment is antiquated and in need of repair. Despite the economic challenges facing Ukranian physicians, they are enthusiastic about the care and services they provide. EMS is well organized and offers services not seen in the United States. Prehospital physicians in Ukraine are viewed as an integral part of the health care system by their hospital-based colleagues.

Education, Medical↗
PubMedDate not supplied

[The spread of HIV/AIDS in Ukraine].

BACKGROUND: In the end-year report 2004 of the European Centre for the Epidemiological Monitoring of AIDS (EuroHIV), the number of newly diagnosed HIV infections in Ukraine ranks second in the WHO European Region after the Russian Federation. METHODS: An analysis of the HIV/AIDS reports from the official epidemiological register of the Ukrainian Centre for AIDS Prevention between 1987 and 2005 was undertaken. In addition, reports from the seroepidemiological monitoring were utilised. RESULTS: According to the Ukrainian Ministry of Health, the cumulative number of reported HIV infections by the end of 2005 amounts to more than 88,900 cases with 13,786 new reports in 2005. The number of newly-registered AIDS cases rose from 45 in 1995 to 4220 in 2005. However, because of many unreported HIV diagnoses, the actual numbers are presumed to exceed the official reports considerably. Most of the infections are associated with injection drug abuse. The second most important route of transmission is sexual contact, also due to an increase in commercial sex. Vertical transmissions from infected mothers to their children rank third. CONCLUSION: HIV was not a significant problem in the Ukraine before 1995. Since 1995 there has been a considerable increase in the number of newly registered HIV cases. At the beginning of the epidemic, HIV was mainly transmitted through sexual contacts in the Ukraine. Since 1995 infected drug users have been the main source of infection in the spread of the epidemic. Unless effective preventive measures are taken, and unless there is more investment in development projects, the HIV/AIDS epidemic in Ukraine could also affect the health system in neighbouring European countries.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Prevention of mother-to-child transmission of HIV infection: Ukraine experience to date.

BACKGROUND: Despite the availability of effective interventions for the prevention of mother-to-child transmission (PMTCT), questions remain regarding implementation of programmes in settings with limited resources. This article sets out to describe the first 2 years of the implementation of the national PMTCT programme in Ukraine. METHODS: National data sources and data from a cohort of pregnant HIV-infected women delivering in 13 centres in Ukraine since 2000 were analysed. RESULTS: Interventions for prevention of MTCT have been implemented as a national programme within Ukraine's well developed infrastructure for maternal and child health. Implementation of an 'opt-out' model of counselling and HIV testing in antenatal clinics resulted in a 97% uptake of women who agreed to be HIV tested. In 2002, approximately 91% of HIV-positive pregnant women received ARV prophylaxis (mainly single-dose nevirapine or short-course zidovudine) for PMTCT. The MTCT rate has decreased from 30% in 2000 to 10% in 2002. The need to scale-up prevention interventions in pregnant women with risky behaviour and late access to medical services was identified in a review of the national programme in 2003. CONCLUSIONS: Further implementation of a comprehensive approach for the prevention of HIV infection in infants, including more extensive ART regimen, as recommended by WHO, would help Ukraine to achieve the strategic goal of virtual elimination of HIV infection in infants by 2010.

Adult↗
PubMed2005

Childhood leukaemia in Belarus, Russia, and Ukraine following the Chernobyl power station accident: results from an international collaborative population-based case-control study.

BACKGROUND: There is little evidence regarding the risk of leukaemia in children following exposure to radionuclides from the Chernobyl Nuclear Power Plant explosion on April 26, 1986. METHODS: This population-based case-control study investigated whether acute leukaemia is increased among children who were in utero or <6 years of age at the time of the Chernobyl accident. Confirmed cases of leukaemia diagnosed from April 26, 1986 through December 31, 2000 in contaminated regions of Belarus, Russia, and Ukraine were included. Two controls were matched to each case on sex, birth year, and residence. Accumulated absorbed radiation dose to the bone marrow was estimated for each subject. RESULTS: Median estimated radiation doses of participants were <10 mGy. A significant increase in leukaemia risk with increasing radiation dose to the bone marrow was found. This association was most evident in Ukraine, apparent (but not statistically significant) in Belarus, and not found in Russia. CONCLUSION: Taken at face value, these findings suggest that prolonged exposure to very low radiation doses may increase leukaemia risk as much as or even more than acute exposure. However the large and statistically significant dose-response might be accounted for, at least in part, by an overestimate of risk in Ukraine. Therefore, we conclude this study provides no convincing evidence of an increased risk of childhood leukaemia as a result of exposure to Chernobyl radiation, since it is unclear whether the results are due to a true radiation-related excess, a sampling-derived bias in Ukraine, or some combination thereof. However, the lack of significant dose-responses in Belarus and Russia also cannot convincingly rule out the possibility of an increase in leukaemia risk at low dose levels.

Age Distribution↗