How do factors known to cause preterm premature rupture of the membranes affect the ultrastructure and integrity of the amnion?

Introduction: Preterm premature rupture of the fetal amniotic membrane (PPROM) is a cause of preterm birth and affects 2% of women worldwide. Causative factors such as uterine contractions and inflammatory mediators such as PGE2 weaken the fetal membrane due to a loss in biomechanical properties. This study investigated the influence of fibre orientation on the mechanical properties of the amniotic membrane (AM) and the effect of cyclical tensile strain (CTS) regimens on the fibre network within the AM as well as on PGE2 production. Methods: AM were collected from women undergoing term elective Caesarean Section at University College Hospital. AM from the cervix and placental regions were stained to identify fibre orientation. Specimens of AM were then subjected to a strain to failure regimen (Bionix 100, MTS). AM were also subjected to CTS using the Bose bioreactor (Bose Enduratec, UK). Assays for GAG, DNA, collagen, elastin and PGE2 were performed and compared to unstrained membrane. Results: The mechanical properties of the AM were dependent on fibre orientation with samples where fibres were strained in parallel being stronger than those strained perpendicular (p=0.0002 comparing the placental region using Student t test). Histological examination of the fibres revealed an abundance of elastin rather than collagen fibres within the AM. CTS reduced collagen and elastin synthesis within the AM, which was most marked in the cervical region (p=0.002, for elastin and p=0.02 for collagen, both in the cervical region). PGE2 production increased in strained specimens, again, most marked in the cervical region (p=0.00001). Conclusion: This study shows that fibre orientation is an important factor which influences the mechanical properties of the AM. Furthermore, elastin may have a larger contribution to membrane integrity than previously thought. CTS influenced the AM to cause weakening by decreasing the collagen and elastin content and increasing PGE2 production

Tissue engineering a fetal membrane

The aim of this study was to construct an artificial fetal membrane (FM) by combination of human amniotic epithelial stem cells (hAESCs) and a mechanically enhanced collagen scaffold containing encapsulated human amniotic stromal fibroblasts (hASFs). Such a tissue-engineered FM may have the potential to plug structural defects in the amniotic sac after antenatal interventions, or to prevent preterm premature rupture of the FM. The hAESCs and hASFs were isolated from human fetal amniotic membrane (AM). Magnetic cell sorting was used to enrich the hAESCs by positive ATP-binding cassette G2 selection. We investigated the use of a laminin/fibronectin (1:1)-coated compressed collagen gel as a novel scaffold to support the growth of hAESCs. A type I collagen gel was dehydrated to form a material mimicking the mechanical properties and ultra-structure of human AM. hAESCs successfully adhered to and formed a monolayer upon the biomimetic collagen scaffold. The resulting artificial membrane shared a high degree of similarity in cell morphology, protein expression profiles, and structure to normal fetal AM. This study provides the first line of evidence that a compacted collagen gel containing hASFs could adequately support hAESCs adhesion and differentiation to a degree that is comparable to the normal human fetal AM in terms of structure and maintenance of cell phenotype

Improvement of Wear Performance of Nano-Multilayer PVD Coatings under Dry Hard End Milling Conditions Based on Their Architectural Development

The TiAlCrSiYN-based family of PVD (physical vapor deposition) hard coatings was specially designed for extreme conditions involving the dry ultra-performance machining of hardened tool steels. However, there is a strong potential for further advances in the wear performance of the coatings through improvements in their architecture. A few different coating architectures (monolayer, multilayer, bi-multilayer, bi-multilayer with increased number of alternating nano-layers) were studied in relation to cutting-tool life. Comprehensive characterization of the structure and properties of the coatings has been performed using XRD, SEM, TEM, micro-mechanical studies and tool-life evaluation. The wear performance was then related to the ability of the coating layer to exhibit minimal surface damage under operation, which is directly associated with the various micro-mechanical characteristics (such as hardness, elastic modulus and related characteristics; nano-impact; scratch test-based characteristics). The results presented exhibited that a substantial increase in tool life as well as improvement of the mechanical properties could be achieved through the architectural development of the coatings

Impaired HMG-CoA reductase activity caused by genetic variants or statin exposure : impact on human adipose tissue, β-cells and metabolome

Inhibition of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase is associated with an increased risk of new-onset type 2 diabetes. We studied the association of genetic or pharmacological HMG-CoA reductase inhibition with plasma and adipose tissue (AT) metabolome and AT metabolic pathways. We also investigated the effects of statin-mediated pharmacological inhibition of HMG-CoA reductase on systemic insulin sensitivity by measuring the HOMA-IR index in subjects with or without statin therapy. The direct effects of simvastatin (20–250 nM) or its active metabolite simvastatin hydroxy acid (SA) (8–30 nM) were investigated on human adipocyte glucose uptake, lipolysis, and differentiation and pancreatic insulin secretion. We observed that the LDL-lowering HMGCR rs12916-T allele was negatively associated with plasma phosphatidylcholines and sphingomyelins, and HMGCR expression in AT was correlated with various metabolic and mitochondrial pathways. Clinical data showed that statin treatment was associated with HOMA-IR index after adjustment for age, sex, BMI, HbA1c, LDL-c levels, and diabetes status in the subjects. Supra-therapeutic concentrations of simvastatin reduced glucose uptake in adipocytes and normalized fatty acid-induced insulin hypersecretion from β-cells. Our data suggest that inhibition of HMG-CoA reductase is associated with insulin resistance. However, statins have a very mild direct effect on AT and pancreas, hence, other tissues as the liver or muscle appear to be of greater importance.Title in Web of Science: Impaired HMG-CoA Reductase Activity Caused by Genetic Variants or Statin Exposure: Impact on Human Adipose Tissue, beta-Cells and Metabolome</p