FEATURES OF THE FORMATION OF INTESTINAL MICROBIOTA AT THE STAGE OF INTRAUTERINE DEVELOPMENT OF THE FETUS

Purpose: to study the features of the parietal intestinal microbiota of pregnant women at risk of intrauterine infection and their effect on the mother-placenta-fetus system and the formation of infant health.Materials and methods. 20 mother-child pairs of a risk group for intrauterine infection with an assessment in mothers: the course of previous pregnancies, the presence of infectious and inflammatory diseases of the pelvic organs, as well as monitoring of the current course of pregnancy, childbirth, the postpartum period and the course of the neonatal period were performed. in their infants: the presence of perinatal infections-cytomegalovirus infection and neonatal herpes, transferred to ARVI, the nature of feeding. All women for 34—37 weeks of gestation and their infants in 15—30 days of life to evaluate the species and quantity composition of the parietal intestinal microbiota used the method of gas chromatography-mass spectrometry with the determination of the concentration of microbial markers (fatty acids of the cell wall of microorganisms) by drop of blood, concentration which is identical to that of the parietal microbiota of the intestine.Results: In all women, an excessive number of microbial markers, predominantly of the Firmicutes type: Anaerobes, Aerobic Actinomycetes, Cocci, Bacilli and some species of microscopic Fungi, were detected in the deficit of priority genera (Bifidobacterium spp., Lactobacillus spp., Eubacterium spp., Propionibacterium), which led to a decrease in the plasmalogen level to 12—39 μmol / L (norm 50) and the excess of endotoxin to 1.5 nanomol / ml (normal 0.5), as well as the excess of the reference values of the markers of the herpes viruses by 3 or more times and their associations.Conclusion: violations of parietal intestinal microbiota of pregnant women and their negative impact on the «mother-placenta-fetus» system and the formation of infant health have been established.

Influence of platelet-activating factor, lyso-platelet-activating factor and edelfosine on Langmuir monolayers imitating plasma membranes of cell lines differing in susceptibility to anti-cancer treatment: the effect of plasmalogen level

Three structurally related but differing in biological activities single-chained ether phospholipids (PAF (platelet-activating factor) and lyso-PAF) and an anti-cancer drug (edelfosine (ED)) were investigated in Langmuir monolayers imitating natural membranes. The aim of the undertaken experiments was to study the influence of these lipids on monolayers mimicking plasma membranes of cell lines differing in susceptibility to the anti-cancer activity of ED, i.e. promyelocytic leukaemia cells (HL-60) and promyeloblastic leukaemia cells (K-562). As these cells differ essentially in the cholesterol/phospholipid ratio and plasmalogen concentration in the membrane, we have carried out systematic investigations in artificial systems of various compositions. The results for model leukaemia cell membrane were compared with data acquired for systems imitating normal leucocytes. Our results show that the level of plasmalogens significantly modulates the influence of the single-chained phospholipids on the investigated systems. The experiments confirmed also that the interactions of ether lipids with a model membrane of HL-60 cells (in biological tests sensitive to ED) have opposite character when compared with K-562, being resistant to ED. Moreover, the values of the parameters characterizing monolayers serving as membrane models (strength of interactions, monolayers fluidity and morphology) proved both sensitivity of these cells to ED and lack of their susceptibility towards PAF. Interestingly, it has been found that lyso-PAF, which is usually described as an inactive precursor of PAF, displays a stronger effect on HL-60 model membranes than ED.

Plasmalogens Inhibit APP Processing by Directly Affectingγ-Secretase Activity in Alzheimer’s Disease

Lipids play an important role as risk or protective factors in Alzheimer’s disease (AD). Previously it has been shown that plasmalogens, the major brain phospholipids, are altered in AD. However, it remained unclear whether plasmalogens themselves are able to modulate amyloid precursor protein (APP) processing or if the reduced plasmalogen level is a consequence of AD. Here we identify the plasmalogens which are altered in human ADpostmortembrains and investigate their impact on APP processing resulting in Aβ production. All tested plasmalogen species showed a reduction in γ-secretase activity whereas β- and α-secretase activity mainly remained unchanged. Plasmalogens directly affected γ-secretase activity, protein and RNA level of the secretases were unaffected, pointing towards a direct influence of plasmalogens on γ-secretase activity. Plasmalogens were also able to decrease γ-secretase activity in humanpostmortemAD brains emphasizing the impact of plasmalogens in AD. In summary our findings show that decreased plasmalogen levels are not only a consequence of AD but that plasmalogens also decrease APP processing by directly affecting γ-secretase activity, resulting in a vicious cycle: Aβ reduces plasmalogen levels and reduced plasmalogen levels directly increase γ-secretase activity leading to an even stronger production of Aβ peptides.