Expression patterns of protein C inhibitor in mouse development

Proteolysis of extracellular matrix is an important requirement for embryonic development and is instrumental in processes such as morphogenesis, angiogenesis, and cell migration. Efficient remodeling requires controlled spatio-temporal expression of both the proteases and their inhibitors. Protein C inhibitor (PCI) effectively blocks a range of serine proteases, and recently has been suggested to play a role in cell differentiation and angiogenesis. In this study, we mapped the expression pattern of PCI throughout mouse development using in situ hybridization and immunohistochemistry. We detected a wide-spread, yet distinct expression pattern with prominent PCI levels in skin including vibrissae, and in fore- and hindgut. Further sites of PCI expression were choroid plexus of brain ventricles, heart, skeletal muscles, urogenital tract, and cartilages. A strong and stage-dependent PCI expression was observed in the developing lung. In the pseudoglandular stage, PCI expression was present in distal branching tubules whereas proximal tubules did not express PCI. Later in development, in the saccular stage, PCI expression was restricted to distal bronchioli whereas sacculi did not express PCI. PCI expression declined in postnatal stages and was not detected in adult lungs. In general, embryonic PCI expression indicates multifunctional roles of PCI during mouse development. The expression pattern of PCI during lung development suggests its possible involvement in lung morphogenesis and angiogenesis

PTX3 predicts severe disease in febrile patients at the emergency department

Objectives: The long pentraxin PTX3 is a promising marker of disease severity in severely ill patients. In order to identify patients warranting critical care as quickly as possible, we investigated the value of PTX3 as a biomarker for disease severity in patients presenting with fever at the emergency department. Methods: Levels of PTX3 were measured in 211 febrile patients at the emergency and the levels were linked to markers of disease severity including admittance to a special care unit, bloodstream infection and congestive heart failure. Results: In comparison to median baseline levels of 2.30 ng/ml (interquartile range 1.66-3.67 ng/ml), levels of PTX3 were significantly elevated in patients admitted to the intensive/medium care unit (median value 44.4 ng/ml, interquartile range 13.6-105.9 ng/ml) and in patients referred to the ward (median value 14.2 ng/ml, interquartile range 7.01-25.1 ng/ml). In addition, PTX3 was associated with duration of hospital stay and acute congestive heart failure. The levels were predictive for bloodstream infection (AUC = 0.71; 95% CI 0.62-0.81). Conclusions: PTX3 may be a useful marker for differentiation of patients with severe disease in patients presenting with fever to the emergency department. (C) 2009 The British Infection Society. Published by Elsevier Ltd. All rights reserve

The effect of PPE-induced emphysema and chronic LPS-induced pulmonary inflammation on atherosclerosis development in APOE*3-LEIDEN mice.

BackgroundChronic obstructive pulmonary disease (COPD) is characterized by pulmonary inflammation, airways obstruction and emphysema, and is a risk factor for cardiovascular disease (CVD). However, the contribution of these individual COPD components to this increased risk is unknown. Therefore, the aim of this study was to determine the contribution of emphysema in the presence or absence of pulmonary inflammation to the increased risk of CVD, using a mouse model for atherosclerosis. Because smoke is a known risk factor for both COPD and CVD, emphysema was induced by intratracheal instillation of porcine pancreatic elastase (PPE).MethodsHyperlipidemic APOE*3-Leiden mice were intratracheally instilled with vehicle, 15 or 30 µg PPE and after 4 weeks, mice received a Western-type diet (WTD). To study the effect of emphysema combined with pulmonary inflammation on atherosclerosis, mice received 30 µg PPE and during WTD feeding, mice were intranasally instilled with vehicle or low-dose lipopolysaccharide (LPS; 1 µg/mouse, twice weekly). After 20 weeks WTD, mice were sacrificed and emphysema, pulmonary inflammation and atherosclerosis were analysed.ResultsIntratracheal PPE administration resulted in a dose-dependent increase in emphysema, whereas atherosclerotic lesion area was not affected by PPE treatment. Additional low-dose intranasal LPS administration induced a low-grade systemic IL-6 response, as compared to vehicle. Combining intratracheal PPE with intranasal LPS instillation significantly increased the number of pulmonary macrophages and neutrophils. Plasma lipids during the study were not different. LPS instillation caused a limited, but significant increase in the atherosclerotic lesion area. This increase was not further enhanced by PPE.ConclusionThis study shows for the first time that PPE-induced emphysema both in the presence and absence of pulmonary inflammation does not affect atherosclerotic lesion development

Travel-related leptospirosis in the Netherlands 2009–2016: An epidemiological report and case series

Background: Leptospirosis is a potentially fatal zoonotic disease that is prevalent in travellers. Here, we describe epidemiological and diagnostic characteristics of all returning travellers diagnosed with leptospirosis in the Netherlands between 2009 and 2016. Furthermore, we present a detailed clinical case series of all travellers with leptospirosis who presented at the Academic Medical Center (AMC) in the same period. Method: We extracted data from the records of the Dutch Leptospirosis Reference Center (NRL) of all cases of leptospirosis in travellers in the Netherlands from 2009 to 2016. Patients who presented at the AMC were identified and clinical data were extracted from the hospital records. Results: 224 cases of travel-related leptospirosis were included. An increase of cases was observed from 2014 onwards. The majority of cases were male (78.1%), and had travelled to South-East Asia (62.1%). Of 41 AMC cases, 53.7% were hospitalised, but most patients had a relatively mild disease course, with no fatalities. A longer delay in diagnosis and treatment initiation existed in hospitalised compared to non-hospitalised patients, suggesting a benefit of early recognition and treatment. Conclusions: Leptospirosis was increasingly observed in returning travellers in the Netherlands, and is a diagnosis that should be considered in any returning febrile traveller

Public-private partnership in Poland. A cosmological journey

A language barrier prevents us from understanding how other cultures look at public administration, as "semantic fields" differ between languages. These differences can never be fully grasped, but what we can do is study what happens when a particular concept crosses the border. In this article we select a concept, public-private partnership, that in recent times migrated from one administrative order, the United States, to another, Poland. We follow this concept on its migration to see how it changes and to find out what these shifts in meaning tell us about the differences between the two social realities involved. © 2010 SAGE Publications

Intratracheal PPE instillation dose-dependently increases alveolar destruction, without affecting pulmonary inflammation.

<p>E3L mice were intratracheally instilled with vehicle, 15 or 30 µg PPE and sacrificed after 24 weeks. Mean linear intercept (B) and air/tissue ratio (C) were determined on sections of the lungs (A). Furthermore, right ventricular (RV) (D) and left ventricular (LV) wall thickness was determined and the ratio was calculated (E). The number of MAC3-positive macrophages (F) and MPO-positive neutrophils (G) in the lung was determined immunohistochemically. Values in B+C are represented as the mean; values in D-G are presented as means ± SEM; n = 12–15; *p<0.05, **p<0.01, ***p<0.001.</p

PPE-induced emphysema combined with low-dose LPS administration induces chronic low-grade pulmonary inflammation, without affecting emphysema.

<p>After intratracheal instillation of vehicle or PPE (30 µg/mouse) in <i>E3L</i> mice, low-dose intranasal LPS (1 µg/mouse) or vehicle was administered during 20 weeks WTD feeding. Total respiratory amplitude was analyzed at 8 and 18 weeks (C and D) after PPE. After sacrifice, mean linear intercept (A) and air/tissue ratio (B) were determined and inflammatory cell influx was determined by immunohistochemical staining of macrophages with F4/80 (E) and neutrophils with MPO (F). Significant effects detected by two-way ANOVA analysis are shown as p-value in textboxes above the figure. Values are presented as means ± SEM; n = 10–15; *p<0.05, **p<0.01, ***p<0.001.</p