Regeneration of Pulmonary Tissue in a Calf Model of Fibrinonecrotic Bronchopneumonia Induced by Experimental Infection with Chlamydia psittaci

Pneumonia is a cause of high morbidity and mortality in humans. Animal models are indispensable to investigate the complex cellular interactions during lung injury and repair in vivo. The time sequence of lesion development and regeneration is described after endobronchial inoculation of calves with Chlamydia psittaci. Calves were necropsied 2–37 days after inoculation (dpi). Lesions and presence of Chlamydia psittaci were investigated using histology and immunohistochemistry. Calves developed bronchopneumonia at the sites of inoculation. Initially, Chlamydia psittaci replicated in type 1 alveolar epithelial cells followed by an influx of neutrophils, vascular leakage, fibrinous exudation, thrombosis and lobular pulmonary necrosis. Lesions were most extensive at 4 dpi. Beginning at 7 dpi, the number of chlamydial inclusions declined and proliferation of cuboidal alveolar epithelial cells and sprouting of capillaries were seen at the periphery of necrotic tissue. At 14 dpi, most of the necrosis had been replaced with alveoli lined with cuboidal epithelial cells resembling type 2 alveolar epithelial cells and mild fibrosis, and hyperplasia of organized lymphoid tissue were observed. At 37 dpi, regeneration of pulmonary tissue was nearly complete and only small foci of remodeling remained. The well-defined time course of development and regeneration of necrotizing pneumonia allows correlation of morphological findings with clinical data or treatment regimen

A bovine model of a respiratory Parachlamydia acanthamoebae infection

The aim of this study was to evaluate the pathogenicity of Parachlamydia (P.) acanthamoebae as a potential agent of lower respiratory tract disease in a bovine model of induced lung infection. Intrabronchial inoculation with P.acanthamoebae was performed in healthy calves aged 2-3 months using two challenge doses: 108 and 1010 bacteria per animal. Controls received 108 heat-inactivated bacteria. Challenge with 108 viable Parachlamydia resulted in a mild degree of general indisposition, whereas 1010 bacteria induced a more severe respiratory illness becoming apparent 1-2 days post inoculation (dpi), affecting 9/9 (100%) animals and lasting for 6 days. The extent of macroscopic pulmonary lesions was as high as 6.6 (6.0)% [median (range)] of lung tissue at 2-4 dpi and correlated with parachlamydial genomic copy numbers detected by PCR, and with bacterial load estimated by immunohistochemistry in lung tissue. Clinical outcome, acute phase reactants, pathological findings and bacterial load exhibited an initial dose-dependent effect on severity. Animals fully recovered from clinical signs of respiratory disease within 5 days. The bovine lung was shown to be moderately susceptible to P.acanthamoebae, exhibiting a transient pneumonic inflammation after intrabronchial challenge. Further studies are warranted to determine the precise pathophysiologic pathways of host-pathogen interactio

A Bovine Model of Respiratory Chlamydia psittaci Infection: Challenge Dose Titration

This study aimed to establish and evaluate a bovine respiratory model of experimentally induced acute C. psittaci infection. Calves are natural hosts and pathogenesis may resemble the situation in humans. Intrabronchial inoculation of C. psittaci strain DC15 was performed in calves aged 2–3 months via bronchoscope at four different challenge doses from 106 to 109 inclusion-forming units (ifu) per animal. Control groups received either UV-inactivated C. psittaci or cell culture medium. While 106 ifu/calf resulted in a mild respiratory infection only, the doses of 107 and 108 induced fever, tachypnea, dry cough, and tachycardia that became apparent 2–3 days post inoculation (dpi) and lasted for about one week. In calves exposed to 109 ifu C. psittaci, the respiratory disease was accompanied by severe systemic illness (apathy, tremor, markedly reduced appetite). At the time point of most pronounced clinical signs (3 dpi) the extent of lung lesions was below 10% of pulmonary tissue in calves inoculated with 106 and 107 ifu, about 15% in calves inoculated with 108 and more than 30% in calves inoculated with 109 ifu C. psittaci. Beside clinical signs and pathologic lesions, the bacterial load of lung tissue and markers of pulmonary inflammation (i.e., cell counts, concentration of proteins and eicosanoids in broncho-alveolar lavage fluid) were positively associated with ifu of viable C. psittaci. While any effect of endotoxin has been ruled out, all effects could be attributed to infection by the replicating bacteria. In conclusion, the calf represents a suitable model of respiratory chlamydial infection. Dose titration revealed that both clinically latent and clinically manifest infection can be reproduced experimentally by either 106 or 108 ifu/calf of C. psittaci DC15 while doses above 108 ifu C. psittaci cannot be recommended for further studies for ethical reasons. This defined model of different clinical expressions of chlamydial infection allows studying host-pathogen interactions

ARTEFACTS: How do we want to deal with the future of our one and only planet?

The European Commission’s Science and Knowledge Service, the Joint Research Centre (JRC), decided to try working hand-in-hand with leading European science centres and museums. Behind this decision was the idea that the JRC could better support EU Institutions in engaging with the European public. The fact that European Union policies are firmly based on scientific evidence is a strong message which the JRC is uniquely able to illustrate. Such a collaboration would not only provide a platform to explain the benefits of EU policies to our daily lives but also provide an opportunity for European citizens to engage by taking a more active part in the EU policy making process for the future. A PILOT PROGRAMME To test the idea, the JRC launched an experimental programme to work with science museums: a perfect partner for three compelling reasons. Firstly, they attract a large and growing number of visitors. Leading science museums in Europe have typically 500 000 visitors per year. Furthermore, they are based in large European cities and attract local visitors as well as tourists from across Europe and beyond. The second reason for working with museums is that they have mastered the art of how to communicate key elements of sophisticated arguments across to the public and making complex topics of public interest readily accessible. That is a high-value added skill and a crucial part of the valorisation of public-funded research, never to be underestimated. Finally museums are, at present, undergoing something of a renaissance. Museums today are vibrant environments offering new techniques and technologies to both inform and entertain, and attract visitors of all demographics.JRC.H.2-Knowledge Management Methodologies, Communities and Disseminatio

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Evaluierung und pathophysiologische Charakterisierung eines bovinen Modells der respiratorischen Chlamydia psittaci Infektion

Chlamydia (C.) psittaci is a gram-negative, obligate intracellular bacterium, capable of inducing respiratory disease and persistent infection. The host range of this zoonotic pathogen includes not only birds and man, but also various wild and domestic mammals. Knowledge about pathogenesis and functional consequences of C. psittaci infection in the mammalian lung has remained elusive to date. The present project aimed to develop, to evaluate and to characterise a bovine model of experimentally induced respiratory C. psittaci infection which might be beneficial for both human and veterinary medicine. Bovines were chosen as the host because (i) bovine C. psittaci infection closely reflects the situation in a natural host, and (ii) the bovine lung is relevant to model functional consequences of ventilatory disorders due to its segmental anatomy and the lack of collateral airways. Moreover, the pathogenetic potential of C. psittaci for bovines and potential transmission routes were evaluated by assessing clinical and immunological variables of health and lung function as well as the shedding of this potentially zoonotic pathogen. A total of 69 Holstein-Friesian calves aged 6 – 9 weeks were included in four separated studies (STUDY 1 – 4) and were challenged as follows: \- Intra-bronchial application of viable C. psittaci, strain DC 15 (n = 35) \- Intra-bronchial application of UV-inactivated C. psittaci, strain DC 15 (n = 6) \- Intra-bronchial application of cell culture medium (n = 25) \- Naïve calves (i.e. sentinels) were socialised with acutely diseased animals due to experimentally induced C. psittaci infection (n =3). Each intra- bronchial application was performed according to a previously developed protocol. In brief, a total volume of 6 mL inoculum/calf was endoscopically administered and distributed in a standardised way into 8 defined bronchi of each animal. In STUDIES 1 & 2, dose response relationships were evaluated up to 3 days post inoculation (dpi). Thus, 14 calves received different doses of viable C. psittaci (106 – 109 inclusion forming units (ifu)/calf). The use of two control groups enabled the separated evaluation of effects mediated by cell culture medium (n = 4) and chlamydial cell components (108 UV-inactivated ifu/calf, n = 6). In STUDIES 3 & 4, time courses and pathophysiological consequences of an acute respiratory C. psittaci infection induced by 108 ifu/calf (n = 21) were assessed in a follow-up study ending at 35 dpi. In addition to the assessment of intra-individual time courses within each calf, a control group was challenged by cell culture medium only (n = 21) for inter- subject comparison. Furthermore, a group of naïve calves (sentinels, n = 3) was socialised with the infected animals, and aimed at evaluating risks and routes of transmission as well as the course of natural infection. In the different studies, systemic host response was assessed by clinical signs, variables of innate immune response, acute phase proteins, and acid-base parameters including electrolytes and metabolites in the peripheral blood. To evaluate pulmonary inflammation, the concentrations of eicosanoids and total protein were measured in broncho-alveolar lavage fluid (BALF) in addition to BALF cytology and pathological as well as histological characterisation of lung lesions. Pulmonary function tests included arterial blood gas analysis, haemoxymetry as well as the assessment of respiratory mechanics, alveolar ventilation and the pattern of breathing. For the latter, non-invasive pulmonary function methods (originally adapted from human medicine and previously evaluated for calves) were used, i.e. impulse oscillometry, volumetric capnography, and helium dilution re-breathing test. Excretion and distribution of the pathogen was assessed by specific nucleic acid-based detection assays (real-time PCR, microarray). The results obtained in the 4 STUDIES can be summarised as follows. Administration of the viable C. psittaci strain succeeded in inducing reproducible infections. Disease outcome was largely dose-dependent. While 106 ifu/calf resulted in mild clinical signs, doses of 107 to 108 ifu/calf induced a moderate respiratory disease, and 109 ifu/calf a severe clinical illness. Also, severity of respiratory and clinical signs, extent and quality of pneumonia, and systemic inflammation increased with increasing challenge doses and resulted in gradually reduced efficacy of pulmonary gas exchange. After inoculation of the finally defined dose of 108 ifu/calf, clinical signs peaked 2 – 3 days post inoculation (dpi). Signs and markers of acute disease subsided considerably, but not completely, within 10 dpi after acute illness. Sentinels acquired the infection but did not develop visible signs of an apparent disease. Thus, two different facets of C. psittaci infection in bovines could be distinguished by the present model: (i) acute clinical disease after experimental challenge and (ii) clinically inconspicuous persistent infection after natural exposure to the pathogen. In both groups, systemic spread and ongoing host-pathogen interactions were detected by chlamydaemia, faecal shedding of the pathogen, and slightly increased levels of monocytes and lipopolysaccharide-binding protein (LBP) in blood, indicating that neither group eliminated the chlamydiae within 5 weeks after exposure. Pathophysiologically, inflammatory cells, mainly neutrophil granulocytes, were recruited into the lung during the acute phase of infection. Pulmonary inflammation resulted in tissue damage, accumulation of detritus and protein rich fluid causing reduced gas exchange, airway obstructions and pulmonary restrictions. Attempts to compensate for alveolar hypoventilation and hypoxaemia included the elevation of both respiratory rate and minute ventilation. Consequences for the acid-base equilibrium were not only determined by pulmonary dysfunctions, compensatory mechanisms or anaerobe metabolism, which are classically assessable by the Hendersen-Hasselbalch approach. A strong ion model revealed mixed acid-base disorders, mediated by metabolic and immunologic influences, i.e. by the reduction of chloride and sodium (assessed by the strong ion difference, SID) and by hypo-albuminaemia and hyper-gammaglobulinaemia (assessed by the sum of non-volatile weak acids, Atot). After experimental challenge, the pathogen was not only detected in lung tissue and blood, but it was also excreted via faeces, nasal excretions and exhaled breath. Despite complete daily cleaning of the animal rooms, contamination sufficed to transmit the infection to naïve sentinels. Although these naturally exposed animals did not develop obvious clinical signs, they became frequent faecal shedders, suggesting a risk of spreading the pathogen under natural conditions. Humoral immune response was generally weak. Only two thirds of experimentally challenged calves developed specific antibodies against C. psittaci detected by immunoblotting. In sentinels, no humoral immune response was observed. In conclusion, the newly introduced large animal model provides a valuable support in elucidating the pathophysiology and complex interactions during pathogenesis of C. psittaci infection in the mammalian lung. In comparative medicine, it can be regarded as a translational model. Pulmonary function tests derived from human medicine and applicable to calves provided comparable data between bovines and humans about pulmonary dysfunction involved in the pathogenesis of this respiratory infection. In veterinary medicine, this biologically relevant model may serve as a suitable basis for studies focusing on vaccine development and treatment evaluation.Einleitung: Chlamydia (C.) psittaci ist ein gram-negatives, obligat intrazelluläres Bakterium, welches in der Lage ist, respiratorische Erkrankungen und persistente Infektionen bei Menschen und Vögeln zu induzieren, und dessen zoonotisches Potential schon lange bekannt ist. Das Wirtsspektrum erweiterte sich mit der Verbesserung molekularbiologischer Nachweismethoden auf diverse Wild- und Haussäugetiere. Bislang sind jedoch die pathogenetische Bedeutung und die funktionellen Konsequenzen der C. psittaci Infektion für die Säugetierlunge nur unzureichend erfasst. Ziele und Projektdesign: Um die Pathogenese der respiratorischen C. psittaci Infektion in der Säugetierlunge besser zu verstehen und um das pathogenetische und epidemiologische Potential von C. psittaci bei Rindern bewerten zu können, bestand das Ziel des vorgestellten Projekts in der Etablierung und Charakterisierung eines bovinen Modells der experimentell induzierten respiratorischen C. psittaci Infektion. Hierfür war zunächst zu klären, ob mit einem C. psittaci-Stamm boviner Herkunft unter experimentellen Bedingungen eine in ihrem Schwergrad von der Inokulationsdosis abhängige, klinisch manifeste Erkrankung im Kalb induzierbar ist (STUDIE 1). Darauffolgend waren die dosisabhängigen Effekte dieser C. psittaci-Infektion auf die Gasaustauschfunktion der Lunge, die angeborenen Immunabwehrmechanismen und die Akute-Phase-Reaktion pathophysiologisch zu charakterisieren (STUDIE 2). Des Weiteren galt es zu eruieren, ob bzw. wie der Erreger sich im Wirtsorganismus ausbreitet, wie lange und über welche Wege er ausgeschieden wird, ob die Infektion spontan von Tier zu Tier übertragbar ist, und wie sich eine spontan erworbene Infektion von einer experimentell induzierte Infektion im Hinblick auf das klinische Bild und die pathophysiologischen Mechanismen unterscheidet (STUDIE 3). Die Evaluierung der durch C. psittaci induzierten pulmonalen Dysfunktionen und Störungen des Säuren-Basen-Gleichgewichts waren Inhalt von STUDIE 4 und dienten dem Ziel, die wesentlichsten Funktionsstörungen auf Organebene aufzuklären, die dem klinischen Bild der induzierten akuten respiratorischen Erkrankung zugrunde liegen. Tiere, Material und Methoden: Insgesamt wurden 69 Holstein-Friesian Kälber im Alter von 6 bis 9 Wochen in das Gesamtprojekt eingeschlossen und wie folgt experimentell belastet: \- intrabronchiale Applikation von lebensfähigen C. psittaci, Stamm DC 15 (n = 35) \- intrabronchiale Applikation von UV-inaktivierten C. psittaci, Stamm DC 15 (n = 6) \- intrabronchiale Applikation von Zellkultur-Medium (n = 25) \- naive Sentinel-Kälber, die mit akut erkrankten Kälbern (nach experimenteller Applikation lebensfähiger C. psittaci) vergesellschaftet wurden (n =3). Alle intrabronchialen Applikationen erfolgten nach einem standardisierten Inokulationsschema, wonach je Tier 6 ml Inokulat in definierten Portionen an 8 definierten Lokalisationen abgesetzt wurden. STUDIEN 1 & 2: Zur Beurteilung der Dosis-Wirkungs-Beziehung erhielten 14 Tiere Dosen von 106 bis 109 einschlussbildenden Einheiten (EBE) lebensfähiger C. psittaci pro Kalb. Der Vergleich zu zwei Kontrollgruppen, denen entweder Zellkultur-Medium (n = 4) oder 108 UV-inaktivierte EBE/Kalb (n = 6) inokuliert wurden, ermöglichte die Bewertung von unspezifischen Effekten. STUDIEN 3 & 4: Auf der Basis einer standardisierte Inokulation von 108 EBE/Kalb (n = 21) wurden die pathophysiologischen Langzeit-Auswirkungen der akuten respiratorischen C. psittaci Infektion sowohl im intra-individuellen Verlauf als auch im Vergleich zu einer mit Zellkultur-Medium inokulierten Kontrollgruppe (n = 21) erfasst (Studienende 35 Tage nach Inokulation (dpi)). Des Weiteren wurden die Ausscheidungs- und Transmissionswege des inokulierten Erregers evaluiert. Die Einbeziehung von naiven Sentinel-Kälbern (n = 3) diente der Dokumentation des Krankheitsverlaufes nach spontan erworbener Infektion. Die Beurteilung der systemischen Wirtsantwort auf den Erreger basierte auf folgenden Kenngrößen: klinischer Score, Parameter der zellulären und humorale Immunantwort, Akute- Phase-Proteine, Parameter des Säuren-Basen-Status sowie Konzentrationen von Elektrolyten und Metaboliten im peripheren Blut. Lokale Entzündungsmechanismen innerhalb der Lunge wurden sowohl durch die Analyse von inflammatorischen Markern in der bronchoalveolären Lavageflüssigkeit (Konzentrationen von Eicosanoiden und Gesamtprotein, Differentialzellbild) als auch mittels pathologischer und histologischer Untersuchungen charakterisiert. Die Erfassung der pulmonalen Dysfunktionen erfolgte quantitativ und qualitativ auf der Basis von arteriellen Blutgasen und Parametern der Hämoxymetrie sowie Parametern der Atmungsmechanik, des Atmungsmusters und der alveolären Ventilation. Für die Lungenfunktionstests standen nicht-invasive Methoden aus der Humanmedizin zur Verfügung (Impuls-Oszilloresistometrie, volumetrische Kapnographie, Helium-Dilution), die zuvor für den Einsatz am wachen Kalb unter Spontanatmung validiert worden waren. Für die Detektion des Erregers im Blut, im Lungengewebe, in Kot-, Nasen- und Augentupfern, sowie in der Ausatem- und Raumluft kamen Polymerase-Kettenreaktion (PCR)-basierte Methoden zum Einsatz (real-time PCR, Microarray). Ergebnisse: Dosis-Wirkungs-Beziehung und Infektionsverlauf Aus der experimentellen Inokulation des vitalen C. psittaci- Stammes resultierten reproduzierbare, von der Erregerdosis abhängige, klinische Bilder einer milden (106 EBE/Kalb), klinisch manifesten (107 bis 108 EBE/Kalb) oder schweren (109 EBE/Kalb) respiratorischen Erkrankung. Mit ansteigenden Erreger-Dosen stiegen zugleich die respiratorischen und klinischen Scorewerte, das Ausmaß der systemischen Entzündungsreaktionen, die Quantität und Qualität der pneumonischen Veränderungen und die Einschränkungen im pulmonalen Gasaustausch. Nach Inokulation des Erregers erreichte die akute klinische Krankheits-Phase 2 – 3 dpi ihren Höhepunkt und klang innerhalb von 7 – 10 dpi wieder ab. Sentinel-Kälber akquirierten die Infektion, bildeten aber keine vergleichbaren klinisch manifesten Symptome aus. Interessanterweise entwickelten sich in beiden Gruppen – also nach dem Abklingen der akuten Krankheitsphase bzw. nach der auf natürlichem Wege erworbenen Infektion – klinisch unauffällige, persistente Infektionsverläufe ohne restitutio ad integrum und ohne komplette Erreger-Elimination. Indikatoren hierfür waren eine bis ca. 5 Wochen nach Erregeraufnahme andauernde Bakteriämie, eine fortwährende Erregerausscheidung im Kot sowie leicht erhöhte Gehalte von Monozyten und Lipopolysaccharid-bindenden Protein im Blut. Pathogenese und Pathophysiologie Während der akuten Erkrankungsphase wurden Entzündungszellen, vor allem neutrophile Granulozyten, in die Lunge rekrutiert. Infektion und Entzündung der Lunge verursachten Gewebeschäden, Anreicherung von Detritus und proteinreicher Flüssigkeit, welche sowohl Obstruktionen der Atemwege als auch eine verminderte Dehnbarkeit des Lungengewebes (bis 11 dpi) zur Folge hatten. Die pathophysiologischen Konsequenzen dieser inflammatorischen Prozesse waren: alveolären Hypoventilation, ein reduzierter pulmonaler Gasaustausch sowie Hypoxämie, in deren Folge kompensatorisch die Atmungsfrequenz und das Atemminutenvolumen anstiegen. Imbalancen des Säuren-Basen-Gleichgewichts resultierten nicht nur aus pulmonalen Dysfunktionen, kompensatorischen Mechanismen oder anaerobem Metabolismus, sondern auch aus der Reduktion von Chlorid- und Natriumkonzentrationen im Blut sowie einer Hypoalbuminämie und Hypergammaglobulinämie. Nach experimenteller Infektion war der Erreger nicht nur im Lungengewebe, sondern auch in Blut, Kot, Nasensekret und in der Ausatemluft nachweisbar. Trotz kompletter täglicher Säuberung der Tierräume reichte diese Kontamination aus, um die Infektion auf naive Sentinel-Kälber zu übertragen. Obwohl diese Tiere nur milde klinische Krankheitszeichen entwickelten schieden sie den Erreger häufig aus, was auch auf ein Verbreitungsrisiko unter natürlichen Haltungsbedingungen schließen lässt. Die humorale Immunantwort war insgesamt schwach ausgeprägt. Nur zwei Drittel der experimentell inokulierten Kälber entwickelten gegen C. psittaci gerichtete Antikörper. Im Gegensatz dazu war bei keinem der 3 Sentinel-Kälber eine humorale Wirtsreaktion nachweisbar. Schlussfolgerungen: Das etablierte Modell leistet einen wertvollen Beitrag zur Aufklärung der Pathophysiologie und der komplexen pathogenetischen Interaktionen der C. psittaci Infektion in der Säugetierlunge. In der vergleichenden respiratorischen Medizin ist es von translationalem Nutzen, insbesondere da die Lungenfunktionstests eine gute Vergleichbarkeit der Daten zwischen Kalb und Mensch erlauben. In der Veterinärmedizin bietet dieses biologisch relevante Tiermodell eine solide Grundlage für weiterführende Studien zur Wirksamkeit von Vakzinen oder medikamentöser Behandlungen

Clinical Global Impression – Corrections (CGI-C) – deutsche Übersetzung

In mehreren Studien wurden hohe Prävalenzen psychiatrischer Störungen in den Justizvollzugsanstalten sowie der Mangel an adäquaten Behandlungsoptionen festgestellt. Jedoch blieb bisher unklar, inwieweit diese Erkrankungen die Betroffenen einschränken. Um den Schweregrad der Erkrankungen erfassen zu können, wurde das allgemeinpsychiatrisch viel genutzte Instrument 'Clinical Global Impression (CGI)' an die Besonderheiten des Vollzugs (CGI-Corrections, CGI-C) angepasst, da dieses Setting die psychiatrische Versorgung und auch Diagnostik vor große Herausforderungen stellt. Gemäß den Leitlinien der WHO wurden die englische Version des Instruments übersetzt sowie 21 Fallvignetten und anschließend die 'Interrater'-Reliabilität mit einer Stichprobe von 20 Personen überprüft. Die Resultate zeigen eine hohe Beurteilerübereinstimmung (Gwet's AC2 0,82, 96%-KI 0,74-0,91, p< 0,001) und nur vereinzelte Anmerkungen der Rater/Raterinnen (20 bei insgesamt 420 Ratings), sodass davon auszugehen ist, dass der CGI-C ein schnelles und effizientes Instrument zur Erfassung der Schwere einer psychischen Erkrankung im Vollzugssetting ist. Ziel des Beitrags ist es, die übersetzte Version des Instruments vorzustellen und zur Verfügung zu stellen. Für die Zukunft sind weitere Untersuchungen gefordert, die sich mit den Testgütekriterien in verschiedenen Populationen (z.B. Frauen, Jugendliche), anderen Ratern/Raterinnen (z.B. Sozialarbeiter, Justizvollzugsbeamte) sowie der Retest-Reliabilität beschäftigen

Circulating and broncho-alveolar interleukin-6 in relation to body temperature in an experimental model of bovine Chlamydia psittaci infection.

In rodent models of experimentally induced fever, the important role of interleukin-6 (IL-6) as a circulating endogenous pyrogen is well established. Studies employing larger animal species and real infections are scarce. Therefore, we assessed bioactive IL-6 in peripheral blood and in broncho-alveolar lavage fluid (BALF) of calves after intra-bronchial inoculation with vital Chlamydia psittaci (Cp), with inactivated Cp, or with BGM cells. Only calves inoculated with vital Cp developed fever (peak at 2-3 days after challenge) and significantly increased IL-6 activity. Controls inoculated with either inactivated Cp or BGM cells also expressed increased bioactive IL-6, but no fever developed. Activity of IL-6 in BALF was significantly higher compared to blood serum. This experimental model of Cp infection revealed no apparent relation between IL-6 in blood and body temperature, but did reveal a relation between IL-6 and other markers of inflammation in BALF. We conclude that a local inflammatory response in the lungs of infected calves caused fever, which developed by mechanisms including other mediators besides IL-6

Regeneration of Pulmonary Tissue in a Calf Model of Fibrinonecrotic Bronchopneumonia Induced by Experimental Infection with Chlamydia psittaci

Pneumonia is a cause of high morbidity and mortality in humans. Animal models are indispensable to investigate the complex cellular interactions during lung injury and repair in vivo. The time sequence of lesion development and regeneration is described after endobronchial inoculation of calves with Chlamydia psittaci. Calves were necropsied 2–37 days after inoculation (dpi). Lesions and presence of Chlamydia psittaci were investigated using histology and immunohistochemistry. Calves developed bronchopneumonia at the sites of inoculation. Initially, Chlamydia psittaci replicated in type 1 alveolar epithelial cells followed by an influx of neutrophils, vascular leakage, fibrinous exudation, thrombosis and lobular pulmonary necrosis. Lesions were most extensive at 4 dpi. Beginning at 7 dpi, the number of chlamydial inclusions declined and proliferation of cuboidal alveolar epithelial cells and sprouting of capillaries were seen at the periphery of necrotic tissue. At 14 dpi, most of the necrosis had been replaced with alveoli lined with cuboidal epithelial cells resembling type 2 alveolar epithelial cells and mild fibrosis, and hyperplasia of organized lymphoid tissue were observed. At 37 dpi, regeneration of pulmonary tissue was nearly complete and only small foci of remodeling remained. The well-defined time course of development and regeneration of necrotizing pneumonia allows correlation of morphological findings with clinical data or treatment regimen