[TREATMENT OF PATIENTS WITH CHRONIC RECURRENT HERPES VIRUS INFECTION OF GENITAL LOCALIZATION: A CLINICAL STUDY OF FORTEPREN PREPARATION].

AIM: Selection of optimal dosage regimen, length of treatment course (frequency of administration), safety, tolerance and clinical effectiveness evaluation of the medical preparation fortepren in patients with chronical recurrent herpes virus infection of genital localization. MATERIALS AND METHODS: The medical product of antiviral and immune modulating effect--fortepren (sodium polyprenyl phosphate) as a 4 mg/ml solution for injections combined with the base course of acyclic nucleoside acyclovir, 400 mg tablets, held studies. 40 male and female patients participated in the study. After a 10-day acyclovir course (400 mg x 3 times a day) for removing the acute phase, 4 groups of 10 individuals were formed: 1--5 ml (20 mg) of fortepren i/m once at day 13 ± 2 after the start of the study after the completion of the treatment of the acute phase of the disease; 2--5 ml (20 mg) fortepren i/m 3 times at an interval of 21 days; 3--2 ml (8 mg) fortepren i/m 3 times at an interval of 21 days; 4 (control)--5 ml of placebo i/m at remission stage 3 times at an interval of 21 days. Increase of the duration of inter-recurrence period, decrease of the severity of the recurrences, state of skin and mucous damage elements, improvements of immunologic parameters were considered during effectiveness evaluation. RESULTS: Significant differences in the frequency of recurrences of genital herpes were shown for 3 months of observation in experimental and control groups. A significant reduction of genital herpes recurrence frequency from 3.52 ± 0.09 (before treatment) to 2.89 ± 0.08 (after treatment) was noted in patients of group 3 (p < 0.001). The frequency of recurrences in the control group was 3.84 ± 0.10, that was higher than the parameters in all the experimental groups. A significant reduction of the rash area was noted in group 3, moreover, a redution of frequency of detection of clinical manifestations of genital herpes in the form of vesicle elements after treatment in groups 2 (p = 0.02) and 3 (p = 0.005) was found. Evaluation of local symptoms has established that burning have caused minimal discomfort for patients of groups 3 and 4 and itch and soreness--of groups 1 and 3. The least pronounced exacerbations were noted in patients of group 3. Intramuscular administration of fortepren preparation was established to result in the increase of titers of leukocyte virus-induced interferon for the whole duration of treatment. CONCLUSION: An intramuscular dose of 2 ml (8 mg) at recurrence stage 3 times at an interval of 21 days after the completion of the 10-day base course of treatment of the acute phase of chronical recurrent herpes virus infection of genital localization using acyclovir was accepted as an optimal dosage regimen. Analysis of the obtained results has shown an acceptable safety profile and a good level of tolerance for fortepren preparation.

[Antiviral activity of polyprenylphosphates in experimental infection caused by hepatitis C virus in vitro].

AIM: Study antiviral effect of sodium polyprenylphosphate (PPP) in experimental infection model caused by hepatitis C virus (HCV) in cell culture. MATERIALS AND METHODS: Cytopathogenic variant of HCV isolated from blood serum of a chronically infected patient was used. HCV infectious dose was 10.0 TCD50. Highly sensitive to cytopathogenic effect of HCV continuous swine embryo kidney cells (SPEV) as 1 day monolayer grown in 24 well plastic plates on 199 medium with 10% calf serum with addition of L-glutamine and antibiotics (100 U/ml) were used. PPP was used in concentrations that do not have cytotoxic effect (from 60 to 7.5 microg in 50 microl); introduced into SPEV cell cultures immediately after infection, 24 hours before or 24 hours after the infection of cells with HCV. Infectious activity of HCV was evaluated by using Reed-Muench formula based on results of medium samples titration obtained 3 days after the infection of cells. RESULTS: PPP was shown to have antiviral properties when added into the cell cultures immediately after the infection with HCV. Under the effect of PPP HCV titers were established to decrease by 3.0 lg (PPV dose of 60 microg) and by 1.9 lg (PPV dose of 30 microg). Positive effect was also obtained for prophylactic use of PPP. When PPP at a dose of 60 microg was introduced 24 hours before the infection of SPEV with HCV, the titer of the virus decreased by 3.5 lg. Prophylactic administration of low doses of the preparation (7.5 and 15.0 microg) also showed evident antiviral effect (decrease of infectious activity of HCV by 3.2 - 2.3 lg, respectively). CONCLUSION: PPP at the doses tested has an ability to reduce concentration of HCV in SPEV cell cultures when added immediately after infection or 24 hours before.

[A preclinical study of the embryotoxic properties of cucumarioside and its effect on adult generative function]. / Doklinicheskoe issledovanie émbriotoksicheskikh svoistv kukumariozida i ego vliianiia na generativnuiu funktsiiu vzroslykh osobei.

The preclinical study of embryotoxicity of a new immunomodulator cucumariosid was carried out. Cucumariosid at long-term use exerts no effect on the generative function of rats, the general condition of pregnant females and the postnatal development of the offspring, possesses no teratogenic action. The use of the drug in the preimplantation period of pregnancy and the implantation period produces the contraceptive effect.

[Cytogenetic study of the mutagenicity of cucumarioside]. / Tsitogeneticheskoe izuchenie mutagennosti kukumariozida.

Mutagenic activity of cucumarioside displaying strong immunomodulating effect was studied. Two cytogenetic tests--mouse bone marrow micronucleus assay and the method for analysis of chromosomal aberrations--were used to evaluate mutagenic activity. Both tests demonstrated negative mutagenic effect.

[Stimulation of nonspecific antibacterial resistance of mice to opportunistic gram-negative microorganisms with triterpene glycosides from Holothuroidea]. / Stimuliatsiia triterpenovymi glikozidami goloturii nespetsificheskoi antibakterial'noi rezistentnosti myshei k uslovnopatogennym gramotritsatel'nym mikroorganizmam.

A total fraction of triterpenic glycosides from Cucumaria japonica named cucumarioside was used as a stimulator of nonspecific resistance to bacterial infections in mice. After intraperitoneal administration to mice subsequently infected with various strains of E. coli and Proteus mirabilis, cucumarioside provided survival of 40 to 90 per cent of the infected animals against 100 per cent in the control group. The protective effect directly depended on the dose of cucumarioside. It was optimal to administer the preparation 3 days before the infection. When the preparation was administered at such periods LD50 for Neisseria meningitidis BT-2 and Salmonella minnesota SF 1111 lowered 5 and 4.3 times, respectively. Therefore, the total fraction of triterpenic glycosides from Far Eastern holothuria had a marked ability to increase natural resistance of the animals to infections caused by various gram-negative organisms.

[Effect of cucumarioside (a triterpene glycoside from the holothurian Cucumaria japonica) on the development of an immune response in mice to corpuscular pertussis vaccine]. / Vliianie kukumariozida (triterpenovogo glikozida iz goloturii Cucumaria japonica) na razvitie immunnogo otveta myshei na korpuskuliarnuiu kokliushnuiu vaktsinu.

The influence of cucumarioside, triterpene glycoside obtained from Cucumaria japonica (Echinodermata, Holoturioidea), or sea cucumbers, on the resistance of mice to Bordetella pertussis infection (with the use experimental pertussis meningoencephalitis as a model) and on the development of immune response to corpuscular pertussis vaccine was studied. The preparation under test was shown to have greatly pronounced immunomodulating properties depending on both the concentration of cucumarioside and the route of its administration, as well as on the dose of pertussis vaccine. When administered orally in a dose of 4 micrograms per mouse and intraperitoneally in doses of 0.04 and 0.0004 micrograms, cucumarioside enhanced the protective effect of corpuscular pertussis vaccine. The use of cucumarioside in a dose of 0.001 micrograms per mouse abolished the suppressive action of large doses of pertussis vaccine in the background rosette-formation test at an early period after immunization and increased number of immune rosettes formed by lymphocytes in the spleen of mice immunized with different doses of the corpuscular vaccine.

[Capacity of triterpene glycosides from holothurians to stimulate antibacterial resistance in a model of experimental murine salmonellosis]. / Sposobnost' triterpenovykh glikozidov iz goloturii stimulirovat' antibakterial'nuiu ustoichivost' na modeli éksperimental'nogo sal'monelleza myshei.

When injected intraperitoneally into mice in doses of 40.0-0.4 microgram, Cucumarioside, the preparation of triterpene glycosides obtained from sea cucumbers (Cusumaria japonica), enhanced the resistance of the animals to the subsequent challenge with Salmonella typhimurium. The study of the duration of the persistence of salmonellae in mice receiving the preparation in a dose of 0.001 microgram revealed a decrease in the contamination of their organs. The same dose of the preparation stimulated the phagocytic activity of peritoneal exudate cells with salmonellae showing decreased cytopathogenic action. This suggests that Cucumarioside enhances nonspecific protective factors, activates the macrophagal system and facilitates the development of complete phagocytosis.

Effect of triterpene glycosides of marine invertebrates on permeability of biological and artificial membranes.

The influence of the triterpene glycosides holothurin and cucumariaside from Holothuria grissi and Cucumaria japonica, respectively, on the parameters of the active transport of calcium ions by vesicles of the sarcoplasmic reticulum and on the permeability of liposomes formed from the total fraction of egg phospholipids was investigated. It was found that at low concentrations these substances decrease the Ca-ATPase activity without noticeably increasing the permeability of the membranes, whereas at high concentrations they cause a sharp increase in the permeability of the membranes of Ca2+ ions.