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The evolution of sexually transmitted infections in the Ukraine.

OBJECTIVES: To evaluate trends in the national and regional reporting of syphilis, gonorrhoea, chlamydia, genital herpes, trichomoniasis, and HIV in Ukraine. METHODS: Annual notification rates of infection per 10(5) population in three regions of Ukraine--Donetsk, Mikolaiv, Chernivtsi--and also among children, adolescents, and pregnant women were used as indicators for the spread of sexually transmitted infections (STIs) in the Ukraine from 1994 to 2000. The estimates were based on a review of medical literature, reported data from STD clinics, and local epidemiological surveys. An analysis of the trends was made. RESULTS: The notification rate of trichomoniasis rose from 284.3 in 1997 to 330.8 in 2000. The same for syphilis was 68.7 per 100,000 population in 1994 peaked in 1996 with 150.9 falling to 91.5 in 2000. The reported incidence of gonorrhoea has been falling recently to 52.7/10(5) in 2000 (a 104.6% decrease since 1994). Chlamydia notification rates, however, rose 2.4-fold between 1995 and 2000 (16.1/10(5) to 54.2/10(5)). In the same period there was a 218% increase the reported incidence of genital herpes. STIs are more common in the eastern industrial regions. In the period 1994-7 there was a dramatic 179-fold increase in the prevalence of HIV/AIDS which has plateaued in subsequent years. By January 2001 a total of 36,600 cases of HIV infection (including 2040 people with AIDS) have been reported. The proportion of HIV acquired through injecting drug use is falling (72.7% in 1997 to 54.2% in 2000) in relation to that acquired through sexual contact. CONCLUSIONS: STIs and HIV are a common cause of morbidity in Ukraine.

Adolescent↗

Collaborative research and research training through the "Family and Children of Ukraine" research program.

Family and Children of Ukraine, the Ukrainian component of the European Longitudinal Study of Pregnancy and Childhood, is a prospective, geographically-based study to evaluate pregnancy outcomes in 8,000 women in five cities in Ukraine and follow the cohort of births through 7 years of age. Family and Children in Ukraine has been the major collaborative research project for the University of Illinois' Fogarty-funded program, International Training and Research in Environmental and Occupational Health. This Fogarty program includes graduate training, U.S.-based training of visiting scientists, in-country training, and collaborative in-country research. Factors that have contributed to the success of the collaboration include: 1) its focus on the environmental health of mothers and children, which is a priority goal for both countries; 2) the adoption of an internationally-endorsed research protocol with strict quality-control criteria, specifically designed for international collaboration; 3) the establishment of an in-country data management center; and 4) the investment in a long-term research program rather than a short-term study. The major obstacles have been the difficult economic situation in Ukraine, which limits in-country research investment, and the difficulty in obtaining U.S. funding for an international research program.

Adult↗

Ukrain(TM), a semisynthetic Chelidonium majus alkaloid derivative, acts by inhibition of tubulin polymerization in normal and malignant cell lines.

Ukrain(TM) has been described as a semisynthetic Chelidonium majus alkaloid derivative, which exhibits selective toxicity towards malignant cells only. Its mechanism of action has hitherto been uncertain. We found that Ukrain(TM) inhibits tubulin polymerization, leading to impaired microtubule dynamics. This results in activation of the spindle checkpoint and thus a metaphase block. The effects of Ukrain(TM) on the growth, cell cycle progression and morphology of two normal, two transformed and two malignant cell lines did not differ. We could thus find no evidence for the selective cytotoxicity previously reported for Ukrain(TM).

Alkaloids↗

Chemical analyses of Ukrain, a semi-synthetic Chelidonium majus alkaloid derivative, fail to confirm its trimeric structure.

Ukrain has been described as a semi-synthetic Chelidonium majus alkaloid derivative, consisting of three chelidonine alkaloids combined to triaziridide. We found the actions of Ukrain to be similar to the Chelidonium alkaloids it is prepared from, and therefore became concerned about its chemical integrity. Chemical analyses of Ukrain by thin layer chromatography, high-performance liquid chromatography and liquid chromatography-mass spectrometry was inconsistent with the proposed trimeric structure and demonstrated that at least some commercial preparations of Ukrain consist of a mixture of C. majus alkaloids (including chelidonine).

Alkaloids↗

Ukrain - a new cancer cure? A systematic review of randomised clinical trials.

BACKGROUND: Ukrain is an anticancer drug based on the extract of the plant Chelidonium majus L. Numerous pre-clinical and clinical investigations seem to suggest that Ukrain is pharmacologically active and clinically effective. We wanted therefore to critically evaluate the clinical trial data in the form of a systematic review. METHODS: Seven electronic databases were searched for all relevant randomised clinical trials. Data were extracted and validated by both authors, tabulated and summarised narratively. The methodological quality was assessed with the Jadad score. RESULTS: Seven trials met our inclusion criteria. Without exception, their findings suggest that Ukrain has curative effects on a range of cancers. However, the methodological quality of most studies was poor. In addition, the interpretation of several trials was impeded by other problems. CONCLUSION: The data from randomised clinical trials suggest Ukrain to have potential as an anticancer drug. However, numerous caveats prevent a positive conclusion, and independent rigorous studies are urgently needed.

Alkaloids↗

A situational picture of HIV/AIDS and injection drug use in Vinnitsya, Ukraine.

BACKGROUND: New and explosive HIV epidemics are being witnessed in certain countries of Eastern Europe, including Ukraine, as well as a rapid and dramatic increase in the supply, use, and negative public health consequences of illicit drugs. A majority of registered HIV cases in Ukraine occur among injection drug users (IDUs), large numbers of whom report HIV risk behaviors such as needle sharing. The purpose of this study was to apply the World Health Organization's Rapid Assessment and Response on Injection Drug Use (IDU-RAR) guide to create a situational picture in the Vinnitsya Oblast, Ukraine, a region with very scarce information about the HIV/AIDS and injection drug use (IDU) epidemics. METHODS: The IDU-RAR uses a combination of qualitative data collection techniques commonly employed in social science and evaluation research to quickly depict the extent and nature of the given health problem and propose locally relevant recommendations for improvement. The investigators focused their assessment on the contextual factors, drug use, and intervention and policy components of the IDU-RAR. A combination of network and block sampling techniques was used. Data collection methods included direct observation, review of existing data, structured and unstructured interviews, and focus group discussions. Key informants and locations were visited until no new information was being generated. RESULTS: The number of registered HIV cases in Vinnitsya has increased from 3 (1987-1995) to 860 (1999-10/2004), 57 of whom have already died. Ten percent of annual admissions to the area's Regional Narcological Dispensary were for opiate disorders, and the number of registered IDUs rose by 20% from 1999 to 2000. The level of HIV/AIDS awareness is generally poor among the general population but high among high-risk populations. Both HIV/AIDS and injection drug use carry a strong stigma in the community, even among medical professionals. There was very little evidence of primary HIV/AIDS prevention efforts, and IDU prevention efforts focused on promotion of anti-drug messages in the schools. CONCLUSION: Given that Ukraine has sparse resources to be devoted to this problem, action recommendations should be prioritized, realistic, and initially targeted to persons in greatest need. The following action recommendations are prioritized by the following categories: First priority: Voluntary Counseling and Testing; Second Priority: Prevention and Education; and Third Priority: Harm Reduction and Treatment. They are provided in this sequence based on what response can realistically be implemented first with limited additional resources and can make the greatest immediate impact. The persons at greatest risk, HIV positive persons and IDUs, should be attended to first.

Journal Article↗

Evaluation of the efficacy of Ukrain in the treatment of breast cancer: clinical and laboratory studies.

The aim of this study was to evaluate the efficacy of different doses of Ukrain in the treatment of 75 breast cancer patients. Patients were divided into three groups. Group I (25 patients) and group II (25 patients) were treated with 50 mg and 100 mg Ukrain, respectively, before surgery. The remaining 25 patients served as controls (no Ukrain treatment). Both clinical observations and laboratory parameters indicate that both doses of Ukrain tested had a similar beneficial effect on patient outcome and may be indicated for presurgical treatment of patients with breast cancer.

Adult↗

Comparative in vitro study of the effects of the new antitumor drug Ukrain and several cytostatic agents on the thiol groups in the tissue of Guerin carcinoma and its resistance to cisplatin variant.

A comparative in vitro study between the effects of Ukrain (a new synthetic thiophosphoric acid derivative of great celandine alkaloids) and alkylating antitumor drugs cyclophosphamid and cisplatin on total thiol content in Guerin carcinoma, Guerin/cis-DDP carcinoma, and in animal livers was carried out. It is shown that Ukrain action on thiol groups in Guerin carcinoma tissue does not differ from that of cyclophospamid and cisplatin to both of which Guerin carcinoma is very sensitive. Once tumor resistance to cisplatin has developed, cisplatin does not react with tumor thiol groups and cyclophosphamid reactions with tumor thiol groups decrease. Reactions of Ukrain with thiol groups of cisplatin resistant tumors increase. This indirectly indicates the increase of tumor sensitivity to this drug. Therefore, the cytotoxicity of Ukrain is similar to that of known antitumor drugs and can probably overcome the cisplatin resistance of the tumor.

Alkaloids↗

Morphometric and kinetic analysis of the growth of experimental sarcoma-45 in the presence of Ukrain.

The effect of the antitumor agent Ukrain on the growth kinetics of the experimental tumor sarcoma-45 was studied by correlation analysis. Sarcoma-45 was implanted into 28 Wistar rats in the subcutaneous layer of a lateral site of the trunk. Fourteen animals received i.v. Ukrain every other day in a dose of 30 mg/kg (0.1 LD50). The other 14 rats served as controls. Macromorphometry of the tumor nodes of sarcoma-45 was carried out every day in both groups. Statistical analysis of morphometric data and plotting of histograms were performed. Regression equations were selected and their parameters determined. A mathematical model was assessed. The effectiveness of Ukrain treatment was analyzed using the equivalent exponent method. Ukrain was proved to be an effective antitumor agent on biological and mathematical models in accordance with standardized instructions for screening.

Alkaloids↗

Six-week treatment with Ukrain in rabbits. Part I: Morphological parameters.

This study was performed to evaluate the effect of 6-week treatment with Ukrain in doses of 0.3, 1.5 and 3.0 mg/kg i.v. on the morphological and biochemical parameters of peripheral blood and morphology of body organs in rabbits. Ukrain application did not change the body organs and total body weight. The drug did not affect biochemical parameters of peripheral blood, except for a minor reduction in the total plasma level and increases in serum uric acid and urea indicating enhanced catabolism of proteins. The peripheral erythrocyte and leukocyte counts were not altered, whereas the percentages of lymphocytes, monocytes, and eozynophils were increased after higher doses of Ukrain. An increase in rod neutrophils and a decrease in the percentage of segmented neutrophils were also noted. These observations indicate a lack of organ toxicity following long-term treatment with Ukrain.

Alkaloids↗

Preliminary pharmacokinetic studies of Ukrain in rats.

Ukrain (thiophosphoric acid derivative of Chelidonium majus L. alkaloids) was administered to rats i.p. at a dose of 28 mg/kg (equivalent to 0.1 LD50). A high performance liquid chromatography (HPLC) method for rapid determination of Ukrain in plasma has been described. It was found that Ukrain rapidly penetrated into the plasma of the rats and the elimination of the drug from the plasma was slower. The results obtained were as follows: absorption rate constant ka = 0.0432 [min-1]; elimination rate constant K = 0.0113 [min-1]; drug half-life t1/2 = 61.32 min; actual concentration of Ukrain in the plasma C = 33 e-0.0113t - 39 e-0.0432t [microgram/ml]; and delay in drug absorption T0 = 5.23 min.

Alkaloids↗

Effect of intermittent three-month treatment with different doses of Ukrain on subregional bone mineral density of the femur of ovariectomized rats.

Ukrain, thiophosphoric acid alkaloid derivative from Chelidonium majus L., was administered i.p. to ovariectomized rats in doses of 7, 14 and 28 mg/kg every other day for 10 days, followed by a 10-day break, and the procedure was performed five times. At the end of long-term treatment with Ukrain (24 h after the last dose of the drug) the rats' right femora were harvested and the bone densitometric parameters of the whole bone and distal metaphyseal and basicervical subregions were assessed using the dual-energy X-ray absorptiometry (DXA) densitometric method. The present results show a decrease in bone mineral density in groups of ovariectomized rats that received 7 mg/kg and 14 mg/kg of Ukrain versus untreated ovariectomized animals. Administration of Ukrain at a dose of 28 mg/kg did not significantly alter bone parameters of ovariectomized rats.

Alkaloids↗

Modification of antinociceptive action of Ukrain by endogenous nitric oxide in the writhing syndrome test in mice.

The effects of L-arginine, the physiological precursor of nitric oxide (NO), and inhibitors of NO-synthase on the antinociceptive action of Ukrain (4.75, 9.5, and 19.0 mg/kg i.p.) were investigated using the writhing syndrome test in mice. It was found that L-arginine (0.1 or 1.0 mg/kg i.p.) significantly decreased or enhanced the antinociceptive effect of Ukrain, depending on the combination administered. In addition, the inhibitors of NO-synthase NG-nitro-L-arginine methyl ester (L-NAME) (1.0 and 10 mg/kg i.p.), 7-nitroindazole (1.0 mg/kg i.p.) and NG-monomethyl-L-arginine acetate (L-NMMA) (1.0 mg/kg i.p.) significantly enhanced Ukrain-induced antinociception. These results suggest that endogenous NO can modify the antinociceptive effect of Ukrain.

Alkaloids↗

Interaction between Ukrain and Naltrexone in the writhing syndrome test in mice.

The interaction between Ukrain and Naltrexone, a nonselective opioid receptor antagonist, was studied in the 'writhing syndrome' test in mice. Naltrexone (1 mg/kg s.c.) was administered i.p. 30 min before Ukrain (2.375, 4.75, 9.5 and 19 mg/kg). In addition, the antinociceptive properties of Ukrain and Naltrexone in 10-day treatment in mice were studied. The results show that the antinociceptive effect of both single dose and prolonged administration of Ukrain is completely antagonized by Naltrexone.

Alkaloids↗

The influence of the novel drug Ukrain on hemo- and immunopoiesis at the time of its maximum radioprotective effect.

Several studies have demonstrated that when Ukrain, a complex preparation of great celandine alkaloids, is used as a preventive agent it increases the survival of animals exposed to whole body gamma-irradiation and enhances the restoration of hemopoiesis. The aim of this study was to describe qualitative and quantitative changes in hemopoietic precursor cells and in myelokaryocytes and leukocytes in the blood caused by Ukrain from its administration to the time the maximal radioresistance potential of the organism is reached. Ukrain was administered i.p. at the dose of 0.2 mg/kg, 24 h prior to investigation. Control animals were injected with saline. Colony-forming units (CFU) were counted in the spleen and bone marrow of the mice, and myelokaryocyte and leukocyte (lymphocyte and granulocyte) counts were determined. The results of this study suggest that Ukrain causes qualitative and quantitative alterations in different pools of hemopoietic cells (stem cells, proliferating cells, maturing cells, and competent cells). These alterations affect the size of the stem cell pool, the kinetics of stem cell proliferation, the direction of their differentiation pathways, the rate of circulation of stem cells and precursor cells, the efficiency of recolonization of cell-depleted sites, and other parameters, which in effect modify standard responses of hemopoiesis and immunogenesis to irradiation so that the radioresistance of the whole organism increases.

Alkaloids↗

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.

Aged↗

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.

Aged↗

Influence of Ukrain and cyclophosphamide administration on HA-1 murine hepatoma and LS lymphoma on aspartic proteinase cathepsin D.

Cathepsin D, the major lysosomal aspartyl proteinase and a mediator of interferon-gamma and tumor necrosis factor-alpha-induced apoptosis, was studied in murine models of LS lymphosarcoma treated by cyclophosphamide (possible apoptosis induction), and HA-1 hepatoma treated by Ukrain (positive antitumor effect). It was found that cyclophosphamide, as well as cyclophosphamide plus Ukrain, increased cathepsin D specific activity in mice with LS lymphosarcoma. Ukrain alone had no effect on cathepsin D activity in LS lymphosarcoma. In HA-1 hepatoma cells cathepsin D activity was not changed compared with intact normal murine liver (day 10) and activity decreased during tumor development (on day 12). Ukrain significantly increased cathepsin D activity in ascitic fluid (day 10) and had a tendency to increase cathepsin D activity in ascitic cells but not to the normal value.

Alkaloids↗