The plasminogen receptor, Plg-RKT, is essential for mammary lobuloalveolar development and lactation.

Essentials Plg-RKT-/- female mice give birth, but no offspring of Plg-RKT-/- female mice survive to weaning. Causal mechanisms of potential lactational failure in Plg-RKT-/- mice are unknown. Plg-RKT regulates extracellular matrix remodeling, cell proliferation, apoptosis, fibrin surveillance. Plg-RKT is essential for lactogenesis and mammary lobuloalveolar development. SUMMARY: Background Lactational competence requires plasminogen, the zymogen of the serine protease, plasmin. Plg-RKT is a unique transmembrane plasminogen receptor that promotes plasminogen activation to plasmin on cell surfaces. Plg-RKT-/- mice are viable, but no offspring of Plg-RKT-/- female mice survive to weaning. Objectives We investigated potential lactational failure in Plg-RKT-/- mice and addressed causal mechanisms. Methods Fibrin accumulation, macrophage infiltration, processing of extracellular matrix components, effects of genetic deletion of fibrinogen, expression of fibrosis genes, and proliferation and apoptosis of epithelial cells were examined in lactating mammary glands of Plg-RKT-/- and Plg-RKT+/+ mice. Results Milk was not present in the stomachs of offspring of Plg-RKT-/- female mice and the pups were rescued by foster mothers. Although the mammary ductal tree developed normally in Plg-RKT-/- glands, lobuloalveolar development was blocked by a hypertrophic fibrotic stroma and infiltrating macrophages were present. A massive accumulation of fibrin was also present in Plg-RKT-/- alveoli and ducts. Although this accumulation was decreased when Plg-RKT-/- mice were made genetically heterozygous for fibrinogen, defects in lobuloalveolar development were not rescued by fibrinogen heterozygosity. Transcriptional profiling revealed that EGF was downregulated 12-fold in Plg-RKT-/- glands. Furthermore, proliferation of epithelial cells was not detectable. In addition, the pro-survival protein, Mcl-1, was markedly downregulated and apoptosis was observed in Plg-RKT-/- but not Plg-RKT+/+ glands. Conclusions Plg-RKT is essential for lactogenesis and functions to maintain the appropriate stromal extracellular matrix environment, regulate epithelial cell proliferation and apoptosis, and, by regulating fibrinolysis, preserve alveolar and ductal patency.

[A new German Scale for Assessing Parental Stress after Preterm Birth (PSS:NICU_German/2-scales)]. / Eine neue deutschsprachige Skala zur Erfassung von elterlichem Stress nach Frühgeburtlichkeit (PSS:NICU_German/2-scales).

Background Preterm birth is known to be a stressful and anxious situation for parents, which might have long-term impact on the psychological health of mothers and even on the development of their preterm infants. Objective The Parental Stressor Scale: Neonatal Intensive Care Unit (PSS:NICU) was developed to assess parental stress after preterm birth through three subscales [1]. The aim of the present study was to examine the psychometric properties and the dimensionality of the German version of the PSS:NICU to develop a reliable German version of the PSS:NICU. Methods For the development (exploratory factor analysis) 100 parents of preterm infants answered the questionnaire. Results The Sights and Sounds subscale was removed from the German version of the PSS:NICU due to low number of items. A PSS: NICU_German/2-scales was developed consisting of 2 subscales: Infant Behavior and Appearance (7 Items, Cronbach's α=0,82) and Parental Role Alteration (6 Items, Cronbach's α=0,87). Conclusions The PSS:NICU_German/2-scales is a reliable and economic scale for the assessment of parental stress after preterm birth.

Deficiency of plasminogen receptor, Plg-RKT , causes defects in plasminogen binding and inflammatory macrophage recruitment in vivo.

Essentials Plg-RKT is a novel integral membrane plasminogen receptor. The functions of Plg-RKT in vivo are not known. Plg-RKT is a key player in macrophage recruitment in the inflammatory response in vivo. Plg-RKT deficiency is not compatible with survival of the species. SUMMARY: Background Plg-RKT is a novel integral membrane plasminogen receptor that binds plasminogen via a C-terminal lysine exposed on the cell surface and promotes plasminogen activation on the cell surface by both tissue plasminogen activator and urokinase plasminogen activator. Objectives To evaluate the role of Plg-RKT in vivo we generated Plg-RKT-/- mice using a homologous recombination technique. Methods We characterized the effect of Plg-RKT deletion on reproduction, viability, health and spontaneous thrombosis and inflammation. Results Plg-RKT-/- mice were viable and fertile. Survival of Plg-RKT-/- mice and Plg-RKT+/+ littermates was not significantly different. However, quite strikingly, all pups of Plg-RKT-/- females died within 2 days of birth, consistent with a lactation defect in Plg-RKT-/- mothers. Additionally, there was a significant effect of Plg-RKT deficiency on the growth rates of female, but not male, mice. In experimental peritonitis studies, Plg-RKT-/- mice exhibited a marked defect in macrophage recruitment. As a contributing mechanism, the capacity of Plg-RKT-/- macrophages for plasminogen binding was markedly decreased. Conclusions These studies demonstrate that Plg-RKT is required for plasminogen binding and macrophage migration in vivo. In addition, Plg-RKT deficiency is not compatible with survival of the species, due to the death of all offspring of Plg-RKT-/- females. This new mouse model will be important for future studies aimed at delineating the role of cell surface plasminogen activation in challenge and disease models in vivo.

Feasibility of long-term cerebral and peripheral regional tissue oxygen saturation measurements.

The aim of this study was to analyse the feasibility of long-term measurements of cerebral (crSO2) and peripheral (prSO2) regional tissue oxygen saturation on the first day of life by determining the amount of artefacts and their influence on rSO2. Near infrared spectroscopy (NIRS) measurements were performed fronto-parietal left (crSO2) and on the right forearm (prSO2). Arterial oxygen saturation (SpO2) was measured by pulse oximetry on the right wrist. Three criteria (C) were defined to identify artefacts (C1: missing values, C2: rSO2 jumping >15%, C3: rSO2 ≥ SpO2). The number of artefacts as a percentage of measurement time and mean rSO2 was calculated after the introduction of each criterion. Measurements were performed in 40 neonates. The number of artefacts in crSO2 measurements was similar after introduction of C1 (7.37 ± 4.64%) and after introduction of all criteria (8.89 ± 4.59%). The number of artefacts in prSO2 measurements after introduction of C1 was 10.83 ± 4.21%, and after introduction of all criteria significantly higher with 17.78 ± 4.27%. After introduction of C1, further criteria did not significantly change rSO2: crSO2 (78.6 ± 1.3% versus 78.5 ± 1.2%) and prSO2 (83.7 ± 0.9% versus 83.5 ± 0.9%). In conclusion, long-term NIRS measurements of crSO2 and prSO2 are feasible, since most artefacts are due to missing values and therefore easy to recognize.