[Clinical and laboratory parallels at pathological and borderline states associated with lipopolysaccharides.]

The review systematizes data on the structure of lipopolysaccharides (LPS) and their role in physiological and systemic pathological processes. The analysis of literature and our own data is of scientific and practical interest for specialists in the field of clinical laboratory diagnostics, anesthesiologists, resuscitators, therapists, immunologists and obstetrician-gynecologists, including studies on the role of LPS in unique three-component systems - «mother-placenta-fetus¼. The prospects of using LPS as immunomodulatory, including for the treatment of infectious diseases, are justified. It is shown that along with their use for the correction of immunodeficiency or the development of new adjuvants and vaccines, it is possible to use their high regulatory activity even at the epigenetic level. The possibility of the prophylactic and therapeutic use of LPS in the context of an alternative solution to the problem of antibiotic resistance of bacteria is discussed.

Non-bulky Lesions in Human DNA: the Ways of Formation, Repair, and Replication.

DNA damage is a major cause of replication interruption, mutations, and cell death. DNA damage is removed by several types of repair processes. The involvement of specialized DNA polymerases in replication provides an important mechanism that helps tolerate persistent DNA damage. Specialized DNA polymerases incorporate nucleotides opposite lesions with high efficiency but demonstrate low accuracy of DNA synthesis. In this review, we summarize the types and mechanisms of formation and repair of non-bulky DNA lesions, and we provide an overview of the role of specialized DNA polymerases in translesion DNA synthesis.

A new approach to prevent HIV transmission: Project Protect intervention for recently infected individuals.

Past research suggests that as many as 50% of onward human immunodeficiency virus (HIV) transmissions occur during acute and recent HIV infection. It is clearly important to develop interventions which focus on this highly infectious stage of HIV infection to prevent further transmission in the risk networks of acutely and recently infected individuals. Project Protect tries to find recently and acutely infected individuals and prevents HIV transmission in their risk networks. Participants are recruited by community health outreach workers at community-based HIV testing sites and drug users' community venues, by coupon referrals and through referrals from AIDS clinics. When a network with acute/recent infection is identified, network members are interviewed about their risky behaviors, network information is collected, and blood is drawn for HIV testing. Participants are also educated and given prevention materials (condoms, syringes, educational materials); HIV-infected participants are referred to AIDS clinics and are assisted with access to care. Community alerts about elevated risk of HIV transmission are distributed within the risk networks of recently infected. Overall, 342 people were recruited to the project and screened for acute/recent HIV infection. Only six index cases of recent infection (2.3% of all people screened) were found through primary screening at voluntary counseling and testing (VCT) sites, but six cases of recent infection were found through contact tracing of these recently infected participants (7% of network members who came to the interview). Combining screening at VCT sites and contact tracing the number of recently infected people we located as compared to VCT screening alone. No adverse events were encountered. These first results provide evidence for the theory behind the intervention, i.e., in the risk networks of recently infected people there are other people with recent HIV infection and they can be successfully located without increasing stigma for project participants.

[Bacterial lipopolsaccharides in pathogenesis of gynecological diseases and obstetric complications].

Analysis of literature data and author studies on the role of lipopolysaccharides (endotoxin) of Gram negative bacteria in women genital tract pathology and obstetric complications is presented. The role of endogenous infection associated with altered microecology of intestinal tract and vaginal biotopes of women in the development of endotoxinemia is discussed. The participation of endotoxin in embryo resorption, delay of intrauterine development and antenatal death of fetus, premature birth, pre-eclampsia, placental dysfunction is examined. The level of endotoxinema and pro-inflammatory cytokines is a marker of chronic endogenous infectious-inflammatory disease of various parts of genital tract with damage of a network of female reproduction system organs.

[The indicators of anti-endotoxin immunity under preeclampsia].

The dysregulation of immune mechanisms of control of gestational process results in a number of obstetric complications, including preeclampsia. Nowadays, there is no detailed description of characteristics of anti-endotoxin immune response under this complication. To evaluate the role of anti-endotoxin immunity in development of preeclampsia the determination of levels of LBP, IgG to core-region LPS, IgA, IgM, IgG in blood plasma was made in 134 pregnant women during II-III terms. The main group (74 pregnant women with preeclampsia) was divided on 2 sub-groups: 50 women with mild preeclampsia of and 24 women with severe preeclampsia. In the first sub-group, in 14 women with mild preeclampsia additionally concentration of soluble form of CD14 and BPI was determined. The control group consisted of 60 pregnant women with physiological course of gestation. The study demonstrated increase of level of LBP up to 14%, double increase of titers IgG to core-region LPS in blood plasma of pregnant women with preeclampsia under standard concentrations of IgA, IgM, IgG. It was demonstrated that under mild preeclampsia an increase of sCD14, BPI occurs as compared with standard values. The results of study reflect characteristic alterations of congenital and adaptive components of anti-endotoxin immunity under preeclampsia.

[Leading role of infection in formation of placental insufficiency].

AIM: Evaluate the role of endotoxinemia in pregnancy complicated with placental insufficiency. MATERIALS AND METHODS: Complex clinical-laboratory examination of 130 pregnant women in 70 of which placental insufficiency was diagnosed (main group) was carried out. The examinees of the main group were divided into 3 subgroups: 36, 20 and 14 pregnant women with compensated, subcompensated and decompensated placental insufficiency, respectively. The control group was composed of 60 pregnant women with physiological course of gestation. Levels of LPS, LPS-binding protein and IgG against core-region, cytokines (TNF-alpha, IL13, IL2, IL4, IL6, IL8, IL10, IFNgamma), C-reactive protein were determined in blood plasma. Infection by Chlamydia trachomatis, Mycoplasma genitalium, Treponema vaginalis, Neisseria gonorrhoeae, Mycoplasma hominis, Ureaplasma urealyticum, Ureaplasma parvum were evaluated by PCR. RESULTS: In the main group in 64.2% of cases the presence of genital tract infection was established, in 47.0%--urinary system. An increase of LPS level, titers of IgG against LPS core-region and LPS-binding protein in blood plasma of pregnant women with placental insufficiency was shown. Cytokine profile in placental dysfunction was characterized by a significant increase of IL1beta, IL8, TNF-alpha Th1 cytokine and IL10 Th2 cytokine concentrations and a decrease of pro-inflammatory IL2, IFNgamma levels. CONCLUSION: The results indicate a leading role of infection in formation of placental dysfunction as well as prove involvement of LPS Gram-negative bacteria in pathogenesis of this complication.

[Systemic endotoxinemia as a pathogenetic factor of pregnancy complication].

AIM: Evaluation of the role of hemocirculation of a bacterial endotoxin in pregnancy complicated with gestosis. MATERIALS AND METHODS: A complex clinical-laboratory examination of 74 pregnant women at the II-III trimester of gestational period including determination of serum cytokine levels (TNFalpha, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IFNgamma), C-reactive protein, LPS, LPS-binding protein and IgG against R-core LPS in blood plasma was performed. RESULTS: In pregnant women with gestosis an increase in endotoxinemia level (p < 0.0001), twofold increase in IgG titers against R-core LPS (p < 0.01) and an increase in LBP concentration by 14% (p < 0.05) without an increase in concentration of C-reactive protein were shown. Cytokine profile in gestosis was characterized by a twofold statistically significant increase of IL-1beta (p < 0.0001), IL-8 (p < 0.0001) pro-inflammatory cytokine levels, a tendency of IL-6 (p = 0.063), TNFalpha (p = 0.13) increase and a decrease of Th1 cytokine concentrations: IL-2 - by 6.5 times (p < 0.0001), IFNgamma--by 2 times (p < 0.0001). CONCLUSION: The results allow to consider gestoses as a manifestation of increased endotoxin translocation into systemic blood flow during gestation, that determines the necessity to improve therapeutic measures in this pathology.

[Character of lipopolysaccharide-binding protein level changes in different pathological conditions and dysbiosis].

AIM: To evaluate diagnostic value of lipopolysaccharide-binding protein (LBP) level in different infectious processes and dysbiosis. MATERIALS AND METHODS: Serum samples of patients with salmonellosis, urogenital chlamydiosis, community-acquired pneumonia, polypous rhinosinusitis, and bacterial vaginosis were studied. RESULTS: LBP level were lower in patients with salmonellosis compared to healthy persons and decreased with increasing severity of the disease. Higher levels of LBP were detected in patients with chlamydiosis. Direct correlation between LBP level and etiology and severity of community-acquired pneumonia was demonstrated. In patients with polypous sinusitis, LBP level correlated directly with duration of disease, and inversely--with duration of remission. Twofold increase of mean LBP blood concentration and its correlation with duration of dysbiosis in patients with bacterial vaginosis were revealed. CONCLUSION: Multidirectional modulation of antiendotoxin defense was observed in different pathological conditions.

[Endotoxinemia and anti-endotoxin immunity in women with bacterial vaginosis].

AIM: To assess the level of endotoxinemia and state of antiendotoxin immunity compared with parameters of humoral immunity in patients with bacterial vaginosis. MATERIALS AND METHODS: Blood sera from 28 women with bacterial vaginosis (main group) and 24 clinically healthy women (control group). Concentration of lypopolysaccharide (LPS) in sera was measured by semi-quantitative gel-clot test using LAL-reagent Endosafe. Concentration of LBP, IgG EndoCAb as well as levels of serum IgA, IgM and IgG were measured by enzyme immunoassay. RESULTS: Conditionally higher level of LPS, 2-fold increase of LBP concentration, 1.7-fold increase of IgG EndoCAb as well as tendency to decrease of IgA level were revealed in sera of women from the main group. Dysbiotic shift in vaginal microecological system of non-pregnant women of child-bearing age was associated with breakthrough of LPS in systemic bloodstream. Registration of vaginosis during pregnancy associated with detection of Chlamydia, possessing LPS similar to enterobacteria, revealed presence of unfavorable variants of prolonged torpid course of dysbiotic signs. CONCLUSION: During torpid forms of bacterial vaginosis, entotoxinemia and abnormalities in anti-endotoxin immunity are revealed, which the need of optimization of its therapy.

[Bacterial vaginosis: etiopathogenetic aspects].

Current microbiological data on the vaginal microecology in healthy women and in patients with bacterial vaginosis are presented in the article. Problems of formation of colonization resistance of vaginal microbiocenosis were discussed. Etiologic role of certain microorganisms and their associations in the pathogenesis of bacterial vaginosis was considered. Pathophysiological processes leading to development of vaginal disbiosis, features of local immune status and molecular specificity of intercellular interactions in the development of adaptive immune response were characterized.