Characterization of lung antigen presenting cells uptake of inhaled antigens

Allergisches Asthma ist eine chronisch entzündliche Erkrankung mit dauerhaft bestehender Überempfindlichkeit. Die Krankheitssymptome sind Atemnot, Sekretion von Schleim, Verkrampfung der Bronchialmuskulatur oder Husten. Diese werden meist durch harmlose Fremdkörper, wie beispielsweise Pollen, Schimmelpilze, Tierhaare, Staub oder Nahrungsmittel hervorgerufen. Diese allergischen Antigene wandern nach der Inhalation in den Respirationstrakt, wo sie von Antigen präsentierenden Zellen erkannt und zerkleinert werden, um eine Immunantwort oder Immuntoleranz zu aktivieren. Unsere Studie beschäftigt sich vorwiegend mit jenen Zellen, die kurz nach Aufnahme von Fremdsubstanzen im Atmungsweg bzw. in der Lunge verweilen. Fraglich ist, mit welchem Phänotyp der Antigen präsentierenden Zellen wir konfrontiert sind. Aus diesem Grund, wurde Mäusen intranasal flüssiges Ovalbumin gekoppelt an Fluorochrome verabreicht, und nach einer bzw. vier Stunden BAL und Lungen entnommen und experimentell untersucht. Zusätzlich haben wir diese Zellen mit den in den Literaturen oft beschriebenen Oberflächenmarkern gefärbt, um die Zellen zu charakterisieren. Es stellte sich heraus, dass sich bereits nach einer und vier Stunden, die Zellen sich im Respirationstrakt befinden und negativ für CD11b, MHC class II, Gr-1 und B220 aber positiv für CD11c, CD205, CD68, CD206, F4/80 und MOMA-2 Marker sind. Zusammengefasst zeigt unsere Studie, dass Antigen präsentierende Zellen sowohl Merkmale von dendritischen Zellen als auch von Makrophagen besitzen. Desweiteren wurde Mäusen intranasal flüssiges Protein vermischt mit Partikeln (India Ink) verabreicht, um zu beobachten, ob die gleichen Zellen beide verschiedene Formen von Fremdkörpern aufnehmen können. Wir sind zu der Erkenntnis gelangt, dass sie diese Eigenschaften besitzen. Diese Zellen scheinen eine eigene Untereinheit der Antigen präsentierenden Zellen zu sein und können eine wichtige Rolle in der Immunantwort und in der Anwendung therapeutischen Strategien spielen.Allergic asthma is a complex inflammatory disease of the airways caused by immune response to common aerosol Ags. The main entrance of these allergic Ags is the respiratory tract where they are recognized and taken up by Ag presenting cells (APCs). This interaction is able to lead to either immune allergic response or immune tolerance. In our study, we were interested in the characterization of APCs which might be involved in causing an allergic response. To determine the phenotype of APCs in the respiratory tract, we instilled i.n. mice with fluorescent-labeled soluble protein (OVA) and particulate Ag (India ink). We evaluated BAL cells and frozen lung tissues under fluorescence microscope. Additionally, cells were stained with common surface markers. Our results indicated that APCs had taken up both soluble and particulate Ags at 1 h and 4 h after instillation. However, surface molecules which were indicated either specific for DCs or for Macs are expressed on the cells. The cells were CD11b-, MHC class II-, Gr-1- and B220- but positive for CD11c, CD205, CD68, CD206, F4/80 and MOMA-2. We couldn’t find any significant differences in the cell phenotype as these cells were positive for both DC and Mac markers. In addition, DCs and Macs were separated by adhesion experiment. We found out that after 24 h of incubation cells are non-adherent. These results suggest that probably more DCs as APCs are situated in the lung. In summary, our data provide evidence that there is a unique subset of lung APCs taking up foreign Ags which share the markers of both DCs and Macs. These APCs could play a key role in regulation of the immune response against inhaled foreign Ag which can imply in understanding the mechanisms leading to immune response and may be useful as a therapeutic strategy

Is clopidogrel better than aspirin following breakthrough strokes while on aspirin? A retrospective cohort study.

ObjectiveThere is insufficient evidence on which to base a recommendation for optimal antiplatelet therapy following a stroke while on aspirin. The objective was to compare clopidogrel initiation vs aspirin reinitiation for vascular risk reduction among patients with ischaemic stroke on aspirin at the time of their index stroke.DesignRetrospective.SettingWe conducted a nationwide cohort study by retrieving all hospitalised patients (≥18 years) with a primary diagnosis of ischaemic stroke between 2003 and 2009 from Taiwan National Health Insurance Research Database.ParticipantsAmong 3862 patients receiving aspirin before the index ischaemic stroke and receiving either aspirin or clopidogrel after index stroke during follow-up period, 1623 were excluded due to a medication possession ratio <80%. Also, 355 were excluded due to history of atrial fibrillation, valvular heart disease or coagulopathy. Therefore, 1884 patients were included in our final analysis.InterventionsPatients were categorised into two groups based on whether clopidogrel or aspirin was prescribed during the follow-up period. Follow-up was from time of the index stroke to admission for recurrent stroke or myocardial infarction, death or the end of 2010.Primary and secondary outcome measuresThe primary end point was hospitalisation due to a new-onset major adverse cardiovascular event (MACE: composite of any stroke or myocardial infarction). The leading secondary end point was any recurrent stroke.ResultsCompared to aspirin, clopidogrel was associated with a lower occurrence of future MACE (HR=0.54, 95% CI 0.43 to 0.68, p<0.001, number needed to treat: 8) and recurrent stroke (HR=0.54, 95% CI 0.42 to 0.69, p<0.001, number needed to treat: 9) after adjustment of relevant covariates.ConclusionsAmong patients with an ischaemic stroke while taking aspirin, clopidogrel initiation was associated with fewer recurrent vascular events than aspirin reinitiation

PHYSIOLOGICAL AND ELECTROMYOGRAPHIC RESPONSES AT THREE LEVELS OF BICYCLE SEAT HEIGHT

Recently, bicycle riding has become one of the most popular exercises. As the use time increased, the risk of pedalling injury raised. Holmes (1994) indicated that inappropriate bicycle saddle height could result in lower limbs injuries. The motivation of this study was to find out the best riding position that could effectively use energy from the physiology and electromyography measures. The oxygen consumption (VO2), heart rate (HR), respiratory exchange ratio (RER) and the muscle activity (electromyography, EMG) from rectus femoris (RF) and biceps femoris (BF) of lower limb were collected during a 6 min cycling trail in three different heights of bicycle saddle. The purpose of this study was to compare the effects of three different types of bicycle seat heights and different perspectives of muscle activity and physiology’s parameters

Did the S.A.R.S. epidemic weaken the integration of Asian stock markets? Evidence from smooth time-varying cointegration analysis

The purpose of this study is to examine the effect of the Severe Acute Respiratory Syndrome (S.A.R.S.) epidemic on the long-run relationship between China and four Asian stock markets. To this end, we first employ the advanced smooth time-varying cointegration model to investigate the existence of a time-varying cointegration relation among these markets and then employ the difference-indifferences approach to analyse whether or not the S.A.R.S. epidemic impacted the long-run relation between China and these four markets during the period 1998–2008, covering 5 years before and after the S.A.R.S. outbreak. Our results support the existence of a time-varying cointegration relation in the aggregate stock price indices, and that the S.A.R.S. epidemic did weaken the long-run relationship between China and the four markets. Therefore, stockholders and policy makers should be concerned about the influence of catastrophic epidemic diseases on the financial integration of stock market in Asia