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RationaleAsthma and Chronic Obstructive Pulmonary Disease (COPD) are the two main chronic airway inflammatory diseases related to aging. Cellular aging is prevented by telomeres and their shortening induces cellular senescence. Human Telomerase Reverse Transcriptase Enzyme (hTERT) can act directly on DNA and prevent telomere shortening. The goal of this study was to assess hTERT expression in the bronchial mucosa of patients suffering from chronic airway obstructive diseases and to relate the hTERT expression to demographics and lung function characteristics.MethodsWe collected bronchial biopsies from 38 patients suffering from chronic airway diseases including 21 severe asthmatics and 17 COPD who underwent bronchoscopy in routine practice. hTERT expression was assessed by immunochemistry and co-immunostaining was performed to identify hTERT positive cells within the different immune cell populations.ResultshTERT expression in airway mucosa was essentially found in structural cells. Among leukocytes, lymphocytes were the principal cells expressing hTERT. On the whole cohort, hTERT expression score was not different between men and women and not influenced by the age nor by the smoking history as reflected by the pack years. Total airway hTERT positive staining score positively correlated with post-bronchodilation (post-BD) FEV1% predicted and FEV1/FVC. (r=0.38, p1/FVC (r=0.37, pConclusionsIn patients with chronic airway diseases, total and lymphocyte hTERT expressions inversely correlate with the degree of airway obstruction and are reduced in patients with fixed airway obstruction, which supports a role of hTERT in airway remodeling.

Alarmins ((IL-25, IL-33 and thymic stromal lymphopoietin (TSLP)) are known to promote Th2 inflammation and could be associated with eosinophilic airway infiltration. They may also play a role in airway remodeling in chronic airway obstructive diseases such as asthma and chronic obstructive pulmonary disease (COPD). IL-23 and IL-36 were shown to mediate the neutrophilic airway inflammation as seen in chronic airway obstructive diseases.The purpose of this project was to determine the expression and the production of these cytokines from induced sputum (IS) in patients with chronic airway obstructive diseases including asthmatics and COPD. The relationship of the mediators with sputum inflammatory cellular profile and the severity of airway obstruction was assessed.The alarmins (IL-25, IL-33 and TSLP) as well as IL-23 and IL-36 concentrations were measured in IS from 24 asthmatics and 20 COPD patients compared to 25 healthy volunteers. The cytokines were assessed by ELISA in the IS supernatant and by RT-qPCR in the IS cells.At protein level, no difference was observed between controls and patients suffering from airway obstructive diseases regarding the different mediators. IL-36 protein level was negatively correlated with sputum eosinophil and appeared significantly decreased in patients with an eosinophilic airway inflammation compared to those with a neutrophilic profile and controls. At gene level, only IL-36, IL-23 and TSLP were measurable but none differed between controls and patients with airway obstructive diseases. IL-36 and IL-23 were significantly increased in patients with an neutrophilic inflammatory profile compared to those with an eosinophilic inflammation and were correlated with sputum neutrophil proportions. None of the mediators were linked to airway obstruction.The main finding of our study is that patients with eosinophilic airway inflammation exhibited a reduced IL-36 level which could make them more susceptible to airway infections as IL-36 is implicated in antimicrobial defense. This study showed also an implication of IL-36 and IL-23 in airway neutrophilic inflammation in chronic airway obstructive diseases.

Eosinophilic inflammation has long been associated with asthma. Looking at systemic and airway eosinophilia, we have recently identified a group of patients exhibiting diffuse eosinophilic inflammation. Among the mechanisms governing eosinophilic inflammation, IgE-mediated mast cell activation is a key event leading to eosinophilia in atopic asthmatics.We conducted a retrospective study on our asthma clinic database containing more than 1500 patients and identified 205 asthmatics with successful sputum induction and concordant eosinophilic phenotype. This phenotype was defined as a sputum eosinophil count≥3% and a blood eosinophils concentration≥400cells/mmThe largest group of asthmatics displaying concordant eosinophilic phenotype had a raised total serum IgE and atopy (45%). IgE-low non-atopic concordant eosinophilic asthma was a predominantly late onset disease, exhibited a more intense airway eosinophilic inflammation (P0.05), required more often maintenance treatment with oral corticosteroids (P0.05) but, surprisingly, had a reduced level of bronchial hyperresponsiveness to methacholine (P0.05) despite similar baseline airway calibre impairment.The more severe airway eosinophilic inflammation in IgE-low non-atopic asthmatics despite similar treatment with ICS and a higher burden of OCS points to a certain corticosteroid resistance in this asthma phenotype.

Although mild to moderate asthma is known to be Th2 driven, cytokines produced in refractory asthma might not fit the classical Th2 pattern.The aim of our study was to assess the cytokine production by sputum and blood cells from 15 refractory asthmatics (American Thoracic Society Criteria) compared to 15 mild untreated and 17 moderate treated asthmatics and 22 healthy subjects. Spontaneous production of interleukin (IL)-4, IL-6, IL-10, interferon-gamma, and tumor necrosis factor alpha was measured by immunotrapping after 24 h sputum or blood cell culture.Moderate and refractory asthmatics were both characterized by a lower production of IL-6 from their airway cells compared to healthy subjects. However, the difference was no longer significant when expressing the results per gram of sputum. No significant difference between the three groups was found regarding other cytokines. As for cytokine production from blood, the three groups of asthmatics exhibited raised production of IL-4 when compared to healthy subjects, and this was true when results were expressed per blood volume or after normalization for total leukocyte cell count. Moderate asthmatics exhibited greater production of IL-10 when compared to refractory asthmatics and healthy subjects when results were normalized for total leukocyte cell count.Sputum cells from moderate and refractory asthmatics release less IL-6. While the systemic overproduction of IL-4 was observed through the all spectrum of asthma severity, moderate asthmatics exhibited greater systemic IL-10 production compared to refractory asthmatics.

In den letzten Jahren zeigte sich immer deutlicher, dass auch nach einer leichten Gehirnerschutterung bedeutungsvolle Langzeitprobleme fur die betroffenen Patienten resultieren konnen. Um ein schlechtes Outcome nach leichter Gehirnerschutterung vorhersehen und allenfalls objektivieren zu konnen, versuchten wir mittels einer prospektiven Studie (n = 73) im Raum Oberengadin anhand der Asservierung des S100β (3 Stunden nach Unfall) einen pradiktiven Wert herauszuarbeiten. Es lies sich jedoch keine Korrelation zwischen erhohten S100β-Werten und PCS (auch nicht einzelner Symptome davon) nachweisen. Somit bleibt die Diagnose eines postkommotionellen Syndroms aufgrund fehlender bildgebender und laborchemischer Korrelation weiterhin sehr schwierig. Ein objektiver Nachweis ist nicht moglich. Die ausfuhrliche Anamnese und klinische Untersuchung zusammen mit einem negativen CT-Befund sind weiterhin das Mittel der Wahl. Abstract: In the past a lot of patients suffered from post-concussive symptoms (PCS) after mild traumatic brain injury (mTBI). The present prospective study (n = 73) was intended to help predict the outcome after mTBI with blood asservation for analysis of S100beta 3 hours after trauma. There was no statistically significant correlation be-tween PCS or even of single symptoms and elevat-ed marker levels. Serum S100beta appears to be a poor predictor of the outcome following mild TBI. Establishing a diagnosis of "PCS" will still be hard in future, since no objective diagnostic -method exists. The most important facts are a precise examination and a history of the patient with a negative CT scan of the head.

Es wird uber die Anwendung der Oberflachenabdruckmethoden vermittels des Siliciumoxyd-Doppelabdruckes auf Bakterien berichtet. Es kamen lufttrockene Bakterien. auf Glasoberflache haftend. und lebende Bakterien auf naturlichem Agar-Substrat zum Abdruck: zur Anwendung gelangten die Kunststoffe Polystyrol und Palavit. Lufttrocknungserscheinuugen bei Bakterien werden gezeigt. und durch den Abdruck lebender Bakterien auf Agar werden Erkenntnisse hinsichtlich der Ausbildung von geiselartigen Strukturen bei Escherichia coli gewonnen.

Einige Fischkrankheiten, bei denen der Verdacht auf ein Virus als Erreger nahelag, wurden elektronenoptisch untersucht. Sowohl bei der Pockenkrankheit als auch bei der infektiösen Bauchwassersucht der Karpfen konnten Elementarkörperchen aufgefunden und elektronenoptisch dargestellt werden. Die E.K. der Fischpocken waren nach Herzberg- Färbung auch im Lichtmikroskop zu sehen. Beim Bauchwassersuchtvirus gelangen einleitende Infektions- und Züchtungsversuche. Diese vorläufigen Ergebnisse bedürfen weiterer Ausarbeitung.

Au moyen d'une technique nouvelle, fondee sur l'emploi de matieres plastiques (Polystyrol et Palavit), l'auteur obtient d'excellentes images de la surface de bacteries vivantes cultivees sur agar-agar. Grâce a cette methode il est possible de mettre en evidence des structures qui n'avaient pas ete decrites jusqu'a ce jour, le «double moulage» restituant fidelement les details caracteristiques de l'original.

Uber Versuche zur Materialbearbeitung mit Elektronen-Strahlen wurde bereits 1953 auf der Tagung der Gesellschaft fur Elektronenmikroskopie in Innsbruck berichtet (2). Die auserordentlich hohe, mit einem fokussierten Elektronenstrahl erzielbare Energiedichte wird zur Erhitzung und Verdampfung von Material verwendet. Auf diese Weise ist es moglich, Material abzutragen und beispielsweise feine Bohrungen herzustellen. Ziel der Arbeit ist die Entwicklung eines Verfahrens zur Materialbearbeitung mit Elektronen-Strahlen, mit dem es moglich ist, an einem Werkstuck formverandernde Bearbeitung innerhalb einer bestimmten Toleranz reproduzierbar auszufuhren.

Bei den ersten praktischen Anwendungen des Verfahrens zur Materialbearbeitung mit Elektronen-Strahlen (1) war es notwendig, sich auf Aufgaben zu beschranken, die mit der etwa 100 W betragenden Leistung der uns zur Verfugung stehenden Elektronenstrahlquellen ausfuhrbar erschienen. Es fanden sich eine ganze Reihe auch technisch interessanter Anwendungen wie beispielsweise die Herstellung feiner Bohrungen, feiner Schlitze oder komplizierter Profilfrasungen. Bei der Ausfuhrung solcher Bearbeitungen stellte es sich als besonders gunstig heraus, einen feinen Elektronenstrahl moglichst hoher Energiedichte mit kreisformigem Querschnitt zu erzeugen und diesen in geeigneter Weise uber die zu bearbeitende Flache zu fuhren. Die Materialabtragung und die dadurch erzielbare Formveranderung hangt damit nicht nur von den Eigenschaften des Elektronen-Strahles ab, sondern sie wird auch von der Art der Bewegung des Strahles uber die zu bearbeitende Flache bestimmt. Dabei ist es moglich, ohne Veranderung der Fokussierungsmittel des Elektronenstrahles, allein durch eine definiert gesteuerte Bewegung des Strahles uber das Werkstuck, in den angegebenen Dimensionen praktisch beliebige Bearbeitungen auszufuhren. Im folgenden wird eine Apparatur zur Herstellung von solchen Elektronenstrahl-Frasungen beschrieben.