EFFECT OF 3-HYDROXYPYRIDINE AND SUCCINIC ACID DERIVATIVES ON BACTERIAL GROWTH IN DISCONTINUOUS CULTURES.

We have studied the effect of domestic derivatives of 3-hydroxypyridine and succinic acid (emoxipine, reamberin, and mexidol) on proliferation of E. coli, S. aureus and E. faecalis in discontinuous cultures (DCs) over a period of 1 or 24 h. It is established that the drugs studied exhibit a biphase effect on the number of bacterial colony-forming units (CFUs) in DCs of E. coli and E.faecalis. This effect is manifested by the initial 1.3 - 3.5-fold decrease in the number of CFUs (after 1-h incubation with drugs) with subsequent return to the control level or 1.8 - 8.8-fold increase over the control level (after 24-h incubation with drugs). In DCs of S. aureus that were incubated with the drugs, we observed 1.1 - 1.95-fold increase in CFU number after I-h incubation and 1.8 - 2.4-fold increase after 24-h incubation. On the whole, the results of our studies demonstrated a positive effect of 3-hydroxypyridine and succinic acid derivatives on bacterial growth in DC. These drugs stimulated increase in CFU number in DCs of test bacterial strains even at concentrations as low as 10⁻9 -10⁻6. The well-known efficiency of 3-hydroxypyridine and succinic acid derivatives in treatment of infectious pathology appears independent of their direct effect on bacterial growth.

Effects of 3-hydroxypyridine derivatives and succinic acid on endometrial leukocyte infiltration, cytokinemia and related affective symptoms during exacerbation of the chronic inflammation of the uterus and adnexa.

We studied the effects of original Russian derivatives of 3-hydroxypyridine and succinic acid (emoxipine, reamberin and mexidol) on the time course of endometrial leukocyte infiltration, blood levels of inflammatory cytokines (IL-1ß and TNF-α), and indicators of affective status in women with exacerbation of the chronic inflammation of the uterus and adnexa. It was found that emoxipine, reamberin, and mexidol included in the complex therapy corrects anxiety and depressive disorders depending on the degree of reduction of endometrial leukocyte infiltration and blood levels of inflammatory cytokines. Derivatives of 3-hydroxypyridine (emoxipine and mexidol) exhibited efficiency, which were superior to derivative of succinic acid (reamberin) in the degree of reduction in endometrial leukocyte and neutrophyl infiltration and in severity of anxiety and depressive disorders. Mexidol, a 3-hydroxypyridine and succinic acid derivative, was most effective and surpassed emoxipine by the degree of reduction of inflammatory cytokine level in the blood and the severity of affective anxiety symptoms in women with exacerbation of the chronic inflammation of the uterus and adnexa.

[Effect of 3-oxypyridine and succinic acid derivatives on endometrial leucocyte infiltration and lipid peroxidation in recrudescence of inflammatory diseases of the uterus and its appendages].

The effect of domestic 3-oxypyridine and succinic acid derivatives (emoxipin, reamberin and mexidol) included in the complex treatment of recrudescence of inflammatory diseases of the uterus and its appendages, as manifested in endometrial leucocyte infiltration (ELI) compared to lipid peroxidation products concentration in blood serum, was assessed in a short-term, prospective placebo-controlled single-blind randomized trial. It has been found that two-week infusions of emoxipin (single dose, 150 mg), reamberin (single dose, 400 ml), and mexidol (single dose, 300 mg) favor a decrease in ELI and influence ambiguously on lipid peroxidation - antioxidant (LPA) system condition in blood serum of patients. It has been found that 3-oxypyridine derivative (emoxipin) decreases the intensity of ELI, but does not affect LPA system condition. Succinic acid derivative (reamberin) is inferior to emoxipin in the degree of decreasing ELI, but reduces the concentration of the antioxidant protein ceruloplasmin. Mexidol, being 3-oxipyridine and succinic acid derivative simultaneously, exceeds reamberin in decreasing ELI, increases concentration of blood antioxidant components (alpha-tocopherol and ceruloplasmin), and decreases the level of primary isopropanol-soluble products of lipid peroxidation.

[Effect of 3-oxypyridine and succinic acid derivatives on clinical manifestations of inflammatory diseases of the uterus and its appendages].

Two-week-long, prospective, placebo-controlled, single-blind randomized study of the effects of intravenous emoxipin (150 mg daily), reamberin (400 ml daily) and mexidol (300 mg daily) infusion on the dynamics of clinical symptoms of non-complicated recrudescence of inflammatory diseases of the uterus and its appendages (IDUA) in comparison to the standard therapy was performed. It was established that emoxipin, reamberin and mexidol administration appreciably improved the clinical state dynamics of women with recrudescence of IDUA. The effect was associated with more pronounced decrease in severity of genital and abdominal symptoms versus standard therapy results.

[Effect of 3-oxypyridine and succinic acid derivatives on affective status in recrudescence of inflammatory diseases of uterus and its appendages].

Short-term, prospective placebo-controlled simple blind randomized study of the effects of 3-oxypyridine and succinic acid derivatives (emoxipin, reamberin, mexidol) on the affective status of females with recrudescence of the inflammatory diseases of uterus and its appendages (IDUA) in comparison to changes of systemic inflammatory response (SIR) markers level in the blood has been conducted. It is established that the inclusion of emoxipin, reamberin and mexidol in complex treatment of IDUA recrudescence reduce depression, anxiety and SIR laboratory signs. Mexidol being both 3-oxypyridine and succinic acid derivative showed the best influence on the dynamics of affective disorders and SIR changes.

[Disturbances in immunological reactivity in women with tuboperitoneal sterility]. / Narusheniia immunologicheskoi reaktivnosti u zhenshchin s trubno-peritoneal'nym besplodiem.

The role of immune disturbances on the systemic and local levels is evaluated and the immunological mechanisms of tuboperitoneal sterility as the basis for the development of the methods of immunocorrection is grounded.

[Etiology and systemic immunity disturbances in patients with tuboperitoneal infertility]. / Etiologiia i kharakter sistemnykh narushenii immuniteta pri trubnoperitoneal'nom besplodii.

The etiological structure of the inflammatory diseases of genitals at different levels of the reproductive tract of women with tuboperitoneal sterility was studied. The study revealed the prevalence of cocci in the cervical canal, anaerobes in the endometrium and chlamydiae in the abdominal cavity (peritoneal fluid, the ovarian capsule, fimbriated ends), as well as the presence of mixed infection in 27% of the patients under study. The specific features of immunity in women with tuboperitoneal sterility were established, which determined the main trends of the subsequent pathogenetically oriented immunocorrection.

[The role of different microorganisms in the genesis of tubal-peritoneal infertility and in immunity]. / Rol' razlichnykh mikroorganizmov v geneze trubno-peritoneal'nogo besplodiia i immunitete.

The character of microflora, directly causing inflammatory process in tuboperitoneal infertility, was studied. The study revealed the prevalence of microbial associations, Chlamydia infection was detected in half of the women, and in 17% of the patients this infection was for the first time detected in the upper section of their reproductive apparatus, which was indicative of the role of Chlamydia infection in the occlusion of the uterine tubes. Opportunistic microflora persisting in persons with defective antimicrobial protection was found. The study of local protective factors in peritoneal fluid revealed the absence of T-cell activity, which was manifested by a low level of sIL-2R and the absence of a significant rise in the level of IL-2 in peritoneal fluid in comparison with that in healthy women. In addition, a decrease in the total complement activity and in the activity of component C3 of the complement was established.

[The characteristics of immunological homeostasis in women with sterility of tuboperitoneal and mixed origins]. / Osobennosti immunologicheskogo gomeostaza u zhenshchin s besplodiem trubno-peritoneal'nogo i smeshannogo geneza.

Immunologic homeostasis was studied in 272 women suffering from sterility of a tuboperitoneal and mixed origin. The detected drastic disorders of immunologic homeostasis were characterized by predominant disorders of primary immunity mechanisms (leukopenia, monocytopenia, lymphopenia, reduced concentrations of IgA and IgM, lysozyme and complement in the blood serum). Types II, III, and IV immunopathologic reactions to uterine tube tissue homologous antigen suggest their contribution to a chronic inflammatory process. A relationship between severity of morphologic changes in uterine tubes and degree of immunity defects and immunopathologic reaction manifestation was revealed.

[The role of chlamydial infection in the genesis of tuboperitoneal sterility in women]. / Rol' khlamidiinoi infektsii v geneze trubno-peritoneal'nogo besplodiia u zhenshchin.

The incidence of chlamydial infection in women with tuboperitoneal sterility is 49.5%. Clinically inflammatory diseases of the pelvic organs in such an infection are characterized by a primary chronic course with frequent recurrences and involvement of the cervix uteri, urethra, internal genitals, with moderately manifest clinical symptoms. Therapy of chlamydial infection should be combined with individual selection of therapeutic measures with due consideration for the inflammatory process phase and site, for the type of pathologic changes, general and immune status.