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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

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

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

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

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

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

Effect of Ukrain on the efficacy of anti-epileptic drugs against maximal electroshock-induced seizures in mice.

It has been found that Ukrain, given intraperitoneally (i.p.), did not influence the threshold for maximal electroconvulsions in mice. Ukrain in doses of 9.5 and 19 mg/kg significantly enhanced the protective efficacy of valproate, decreasing the ED50 values. However, Ukrain had no effect on the protection provided by diazepam, carbamazepine, diphenylhydantoin and phenobarbital. The combined treatment with Ukrain and anti-epileptic drugs did not cause any signs of toxicity.

Alkaloids

Chelidonium majus L. (Ukrain) in the treatment of cancer patients.

Ukrain, a semi-synthetic thiophosphoric acid compound of alkaloid chelidonine isolated from Chelidonium Majus L., Tris(2-([5bS-(5ba,6b,12ba)]-5b,6,7,12b,13,14- Hexahydro-13-methyl][1,3]-benzodioxolo[5,6-c]-1,3-dioxolo[4, 5- i]phenanthridinium-6-ol]-Ethaneaminyl) Phosphinesulfide 6HCl, causes a regression of tumours and metastases in many oncological patients. More than 400 documented patients with various carcinomas in different stages of development have been treated with Ukrain. The authors report on only three different cases treated with preparation Ukrain. Ukrain can be helpful in improving the general condition and prolonging life by reduction of the tumour progression and its immunomodulating effect on the organism.

Adenocarcinoma

Effect of single and three months treatment with Ukrain on aminotransferases (ALT and AST) and on the serum protein level in rodents.

The influence of Ukrain on the activity of aminotransferases (ALT and AST) and on the serum total protein content was estimated in mice and rats of both sexes receiving single or repeated doses of the drug. It was found that one hour after intraperitoneal (i.p.) administration of Ukrain no characteristic changes were recorded in the activity of the investigated enzymes, or in the serum protein content of animals of either sex. Similar effects were observed after three months treatment with Ukrain in rats of either sex. Only in mice receiving Ukrain for three months was a rise in ALT and AST activity found. No particular changes were observed in the total serum protein level, except for a small decreases in the sera of male mice.

Alanine Transaminase

Interaction between Ukrain and aminophenazone in analgesic tests in rodents.

The effect of Ukrain on the analgesic activity of aminophenazone was studied in mice and rats. Antinociceptive action induced by aminophenazone in doses of 50 or 100 mg/kg intraperitoneally (i.p.) was determined by using the writhing syndrome, hot-plate tests and tail-flick latency. The action of aminophenazone was significantly enhanced by Ukrain in the writhing syndrome test and in the tail-flick test. Antinociceptive action of aminophenazone was decreased by Ukrain in the hot-plate test in mice. These results suggest that Ukrain, given simultaneously with aminophenazone, changes susceptibility of animals to nociceptive reaction in the tests performed.

Acetates

[Sensitivity to antibacterial preparations of the pseudotuberculosis bacteria isolated on the territory of the Ukraine].

Sensitivity of 92 strains of the causative agent of pseudotuberculosis isolated in the Ukraine was studied with respect to 26 antibacterial drugs. It was found that the strains of the pseudotuberculous bacteria were sensitive to 17 drugs, i.e. benzylpenicillin, ampicillin, carbenicillin, cephaloridin, chloramphenicol, tetracycline, streptomycin, neomycin, monomycin, kanamycin, gentamicin, polymyxin, colistin, furadontin, nalidixic acid, sulfisoxazol and septrin. No differences in the sensitivity of the strains isolated in various districts of the Ukraine and from various sources were found. By their antibiotic sensitivity the strains isolated in the Ukraine did not differ from the cultures isolated in other districts of the USSR and abroad.

Animals

Teratological evaluation of Ukrain in hamsters and rats.

The compound Ukrain, containing thiophosphoric acid alkaloid derivatives from the plant Chelidonium majus L., was given intramusculary (i.m.) on days 6-11 of gestation to hamsters and on days 6-15 of gestation to rats in doses of 0.1, 1.67 and 28 mg/kg daily. No clinical signs of toxicity were found in treated animals and no teratogenic effect could be noted in either species. Such parameters as the number of corpora lutea, implantation sites, pre and post-implantation losses, number of live foetuses per litter, placental weight, foetal weight and crown-rump length were not significantly different between the Ukrain treated rats and the controls. Slight embryotoxic effects (increased post-implantation losses) and in consequence decreased number of average litter size were noted in hamsters exposed to Ukrain at doses which were otherwise not embryotoxic to rats.

Alkaloids

Evaluation of mutagenic, genotoxic and transforming properties of Ukrain.

Evaluation of mutagenic and genotoxic properties of Ukrain was on the basis of the Ames and micronucleus tests. Ukrain was investigated for its ability to induce morphological transformation of embryonic cells of the Syrian hamster. Under the experimental condition used in this study, Ukrain was found to be non-mutagenic and non-genotoxic, and furthermore did not induce morphological cell transformation.

Alkaloids

Clinical studies of Ukrain in healthy volunteers (phase 1).

Phase I of a clinical study of Ukrain was performed in 19 healthy outpatient volunteers. Their general clinical conditions were evaluated, as well as the following parameters: biochemical, haematological, immunological, electrolyte and trace elements, neopterin, immune complexes and non specific blocking factors. Ukrain was administered intramuscularly (i.m.) or intravenously (i.v.) every one, two or three days in doses of 5 to 50 mg for 7 to 40 days. In one case the drug was administered for three years in the dose of 5 to 50 mg/injection in repeated courses. During the investigation no significant changes were found in clinical states. During the intramuscular injections the volunteers felt only localized pain; some reported drowsiness, increased thirst and polyurea. There was a slight, insignificant increase in body temperature and negligible decrease of blood pressure in some cases. In conclusion, it can be said that Ukrain is well tolerated in healthy volunteers in the doses of 5, 10, 20, and 50 mg/injection, even during prolonged (up to three years) administration.

Adult

Effect of single and prolonged administration of Ukrain on prolactin concentration in rats.

The effect of single and prolonged administration of Ukrain on the serum prolactin concentrations in rats of both sexes was investigated. One hour after intraperitoneal (i.p.) administration of Ukrain in rats, in doses of 7, 14 and 28 mg/kg, the drug did not affect their serum prolactin concentration. Only in a dose of 28 mg/kg did this drug decrease serum prolactin in a group of female rats. Repeated i.p. treatment (once daily for three months) with 7, 14 and 28 mg/kg of Ukrain significantly increased the serum prolactin concentration in rats of both sexes. The most marked effect was observed in the group of female rats.

Alkaloids

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.

Acute-Phase Proteins

[Possibilities and prospects of the use of DNA analysis in the diagnosis and prevention of inherited disease in the Ukraine].

The results from molecular genetic analysis of some mutations in the 10th and 11th exons of cystic fibrosis transmembrane regulator (CFTR) gene as well as of deletions in the 8, 17, 19, 43, 50, 60th exons of dystrophin gene in 61 CF-families and 21 DMD-families from different Ukraine regions are presented. It was shown that delta F508 frequency of CF-patients was 59.2%, the frequencies of S5491, G551D and K533X were about 1%. The frequency of delta F508-carriers analysed among 365 healthy donors from different regions of Ukraine was 1:40. The analyzed deletions of dystrophin gene were revealed only among 6 DMD-patients. The associations of analyzed mutations of CFTR gene and DMD-gene with RELP's in 4 loci of chromosome 7 and 2 loci of X-chromosome, respectively, were found. The results of prenatal diagnosis of cystic fibrosis and DMD are presented.

Chromosomes, Human, Pair 7

[The results and prospects of preventing arterial hypertension in Ukraine].

An analysis is presented of the status of arterial hypertension prophylaxis in the Ukraine. Drawbacks in solution of this problem are discussed: diagnosis is incomplete, prophylactic management of hypertensive disease is inadequate. Ways and means of improving the diagnosis and prophylaxis of hypertensive disease in the Ukraine including better remuneration of the medical personnel and interests of the population in preserving their health are discussed.

Age Factors