Maternal monocytes in pregnancy and preeclampsia in humans and in rats

AbstractMonocytes are short-lived cells, arising from the bone marrow and maturing in the circulation. They play an important role in immune responses and are thought to be important for healthy pregnancy. In humans, 3 subpopulations of monocytes have been identified: classical, intermediate and non-classical monocytes. These subpopulations have different functions and phenotypical characteristics. Healthy pregnancy is characterized by a pro-inflammatory condition, with increased numbers of monocytes and monocyte activation as well as with increased numbers of intermediate monocytes and decreased numbers of classical monocytes. This may suggest monocyte maturation. Preeclampsia is an important pregnancy complication characterized by hypertension and proteinuria developing in the second half of pregnancy. The pathophysiology of preeclampsia is associated with further activation of the inflammatory response, further activation of monocytes and further monocyte maturation. In the present review we focus on the role of monocyte activation and maturation in healthy and preeclamptic pregnancy

Mitochondrial function in immune cells in health and disease

One of the main functions of mitochondria is production of ATP for cellular energy needs, however, it becomes more recognized that mitochondria are involved in differentiation and activation processes of immune cells. Upon activation, immune cells have a high need for energy. Immune cells have different strategies to generate this energy. In pro-inflammatory cells, such as activated monocytes and activated T and B cells, the energy is generated by increasing glycolysis, while in regulatory cells, such as regulatory T cells or M2 macrophages, energy is generated by increasing mitochondrial function and beta-oxidation. Except for being important for energy supply during activation, mitochondria also induce immune responses. During an infection, they release mitochondrial danger associated molecules (DAMPs) that resemble structures of bacterial derived pathogen associated molecular patterns (PAMPs). Such mitochondrial DAMPS are for instance mitochondrial DNA with hypomethylated CpG motifs or a specific lipid that is only present in prokaryotic bacteria and mitochondria, i.e. cardiolipin. Via release of such DAMPs, mitochondria guide the immune response towards an inflammatory response against pathogens. This is an important mechanism in early detection of an infection and in stimulating and sustaining immune responses to fight infections. However, mitochondrial DAMPs may also have a negative impact. If mitochondrial DAMPs are released by damaged cells, without the presence of an infection, such as after a trauma, mitochondrial DAMPs may induce an undesired inflammatory response, resulting in tissue damage and organ dysfunction. Thus, immune cells have developed mechanisms to prevent such undesired immune activation by mitochondrial components. In the present narrative review, we will describe the current view of mitochondria in regulation of immune responses. We will also discuss the current knowledge on disturbed mitochondrial function in immune cells in various immunological diseases

Pancreatic Beta-Cell Purification by Altering FAD and NAD(P)H Metabolism

Isolation of primary beta cells from other cells within in the pancreatic islets is of importance for many fields of islet research. However, up to now, no satisfactory method has been developed that gained high numbers of viable beta cells, without considerable alpha-cell contamination. In this study, we investigated whether rat beta cells can be isolated from nonbeta endocrine cells by manipulating the flavin adenine dinucleotide (FAD) and nicotinamide-adenine dinucleotide phosphate (NAD(P)H) autofluorescence. Beta cells were isolated from dispersed islets by flow cytometry, based on their high FAD and NAD(P)H fluorescence. To improve beta cell yield and purity, the cellular FAD and NAD(P)H contents were altered by preincubation in culture media containing varying amounts of D-glucose and amino acids. Manipulation of the cellular FAD and NAD(P)H fluorescence improves beta cell yield and purity after sorting. This method is also a fast and reliable method to measure beta cell functional viability. A conceivable application is assessing beta cell viability before transplantation

Impaired trophoblast invasion and increased numbers of immune cells at day 18 of pregnancy in the mesometrial triangle of type 1 diabetic rats

AbstractIntroductionType 1 diabetes (T1D) is associated with adverse pregnancy outcome, usually attributed to hyperglycemia. Recently, we showed that pregnancy outcome in normoglycemic T1D rats was characterized by decreased fetal and placental weight, suggesting impaired placental development. In the present study, we tested the hypothesis that trophoblast invasion and spiral artery (SA) remodeling is impaired in T1D rats ant that this is associated with aberrant local presence of NK cells and macrophages in the mesometrial triangle (MT).MethodsPlacentae with MT from pregnant biobreeding diabetes-prone (BBDP; T1D model) rats, control biobreeding diabetes-resistant (BBDR) and Wistar-rats were dissected at day 18 of gestation and stained for trophoblast invasion, SA remodeling, uNK cells and macrophages.ResultsInterstitial trophoblast invasion and SA remodeling was impaired in BBDP-rats vs. control rats, coinciding with increased presence of NK cells and an increased iNOS+/CD206+ ratio of macrophages.DiscussionDecreased fetal and placental weight in BBDP-rats was associated with diminished interstitial trophoblast invasion and less optimal SA remodeling, increased numbers of NK cells and increased iNOS+/CD206+ macrophage ratio in the MT of BBDP-rats.ConclusionsThe impaired trophoblast invasion and SA remodeling may be due to an aberrant local immune-response and may result in damage to the fetal placenta and insufficient supply of nutrients towards the fetus with eventually decreased fetal weight as a consequence

Проблема правової культури в історії філософсько-педагогічної думки

(uk) Стаття присвячена проблемі правової культури в історії філософсько-педагогічної думки

Pectin limits epithelial barrier disruption by Citrobacter rodentium through anti-microbial effects

SCOPE: C. rodentium is the murine equivalent of Enteropathogenic Escherichia. coli (EPEC) and Enterohemorrhagic Escherichia coli (EHEC) which induce damage to the intestinal epithelial barrier that results in diarrhea and intestinal inflammation. Dietary fibre intake can be an effective approach to limit epithelial damage by these enteric pathogens. Therefore, the protective effect of dietary fibre pectin against dysfunction of epithelial barrier integrity upon C. rodentium infection was investigated. METHODS AND RESULTS: Pectins that structurally differed in the degree and distribution of methylesters were tested on barrier protective effects on epithelial cells against C. rodentium by measuring transepithelial electrical resistance and lucifer yellow fluxes. All three pectins protected the epithelial barrier from C. rodentium induced damage in a structure-independent manner. These barrier protective effects were also independent of pectin-induced TLR2 activation. Furthermore, the pectins induced anti-adhesive effects on C. rodentium by interacting with C. rodentium and not with epithelial cells. This may be explained by antimicrobial effects of pectins on C. rodentium and not on other enteric bacteria including Lactobacillus plantarum and E. coli. A competition ELISA for binding of C. rodentium to pectin supported this finding as it showed that pectin interacts strongly with C. rodentium, whereas it interacts weakly or not with L. plantarum or E. coli. CONCLUSION: These findings demonstrate that pectin protects the epithelial barrier from C. rodentium induced damage by inducing anti-microbial effects

Level statistics of XXZ spin chains with a random magnetic field

The level-spacing distribution of a spin 1/2 XXZ chain is numerically studied under random magnetic field. We show explicitly how the level statistics depends on the lattice size L, the anisotropy parameter $\Delta$, and the mean amplitude of the random magnetic field h. In the energy spectrum, quantum integrability competes with nonintegrability derived from the randomness, where the XXZ interaction is modified by the parameter $\Delta$. When $\Delta \ne 0$, the level-spacing distribution mostly shows Wigner-like behavior, while when $\Delta$=0, Poisson-like behavior appears although the system is nonintegrable due to randomness. Poisson-like behavior also appears for $\Delta \ne 0$ in the large h limit. Furthermore, the level-spacing distribution depends on the lattice size L, particularly when the random field is weak.Comment: 4 pages, 3 figures, to be published in Phys. Rev.

Interaction-induced chaos in a two-electron quantum-dot system

A quasi-one-dimensional quantum dot containing two interacting electrons is analyzed in search of signatures of chaos. The two-electron energy spectrum is obtained by diagonalization of the Hamiltonian including the exact Coulomb interaction. We find that the level-spacing fluctuations follow closely a Wigner-Dyson distribution, which indicates the emergence of quantum signatures of chaos due to the Coulomb interaction in an otherwise non-chaotic system. In general, the Poincar\'e maps of a classical analog of this quantum mechanical problem can exhibit a mixed classical dynamics. However, for the range of energies involved in the present system, the dynamics is strongly chaotic, aside from small regular regions. The system we study models a realistic semiconductor nanostructure, with electronic parameters typical of gallium arsenide.Comment: 4 pages, 3ps figure

Unexpected non-Wigner behavior in level-spacing distributions of next-nearest-neighbor coupled XXZ spin chains

The level-spacing distributions of XXZ spin chains with next-nearest-neighbor couplings are studied under periodic boundary conditions. We confirm that integrable XXZ spin chains mostly have the Poisson distribution as expected. On the contrary, the level-spacing distributions of next-nearest-neighbor coupled XXZ chains are given by non-Wigner distributions. It is against the expectations, since the models are nonintegrable.Comment: 4 pages, 4 figures, to be published in Physical Review