Sonographie der Lunge und Analyse der Atmungsmechanik mittels Impuls-Oszilloresistometrie beim lungengesunden und pneumoniekranken Ferkel und Läuferschwein

Carmen Klein: Sonographie der Lunge und Analyse der Atmungsmechanik mittels Impuls-Oszilloresistometrie beim lungengesunden und pneumoniekranken Ferkel und Läuferschwein Institut für Bakteriologie und Mykologie der Veterinärmedizinischen Fakultät der Universität Leipzig Bundesinstitut für gesundheitlichen Verbraucherschutz und Veterinärmedizin (BgVV), Fachbereich 4 in Jena eingereicht im Mai 1999, verteidigt am 16. November 1999 (157 Seiten, 52 Abbildungen, 34 Tabellen, 285 Literaturstellen; Anhang mit: 62 Seiten, 15 Abbildungen und 50 Tabellen) Mit der Sonographie der Lunge und der Impuls-Oszilloresistometrie (IOS - engl.: Impulse Oscilloresistometry System) wurden erstmals zwei nichtinvasive diagnostische Verfahren auf ihre Anwendbarkeit und Aussagefähigkeit bei lungengesunden und pneumoniekranken Absatzferkeln und Läuferschweinen bis zu einer Körpermasse von ca. 50 kg geprüft. Die sonographische Untersuchung der Lunge wurde an insgesamt 45 lungengesunden bzw. pneumoniekranken Schweinen durchgeführt. Dazu wurden die Tiere mit 2,0 mg/kg KM Diazepam sediert. Eine Studie an sechs klinisch gesunden Schweinen gab Aufschluß über die Ausdehnung des bei dieser Tierart sonographisch erreichbaren Lungenfeldes. Die bei Pneumonien häufig betroffenen kranioventral gelegenen Lungenabschnitte waren sonographisch gut zu erreichen. Die bei der sonographischen Untersuchung der Lunge des Schweines nachgewiesenen Befunde zeigten eine gute Übereinstimmung mit den in der Literatur an anderen Spezies beschriebenen Resultaten. Beim Schwein wurden folgende Befundbilder abgegrenzt: ? keine Veränderungen : sonographisch o.b.B. ? geringgradige Veränderungen: Kometenschweifartefakte in geringer Ausprägung ? mittelgradige Veränderungen: Kometenschweifartefakte und Konsolidierungen oder echogenes Grundmuster mit Kometenschweifartefakten ? hochgradige Veränderungen: echogenes Grundmuster oder echogenes Grundmuster mit Abszeß oder Nekrose Die Befunde der sonographischen Untersuchung der Lunge wurden bei 34 Schweinen den entsprechenden pathologisch-anatomischen Befunden zugeordnet. Pathologisch-anatomisch unverändertes Gewebe stellte sich mit einer Wahrscheinlichkeit (Sensitivität) von 95,65 % ohne bzw. mit nur geringradigen sonographischen Veränderungen dar. Bei pathologisch-anatomisch verändertem Gewebe wurden mit einer Wahrscheinlichkeit von 74,62 % (Sensitivität) mittel- und hochgradig veränderte sonographische Befundbilder festgestellt. In die histologische Untersuchung wurden insgesamt 49 Gewebeproben einbezogen. Rückschlüsse vom sonographischen Befund auf die Art der histologisch diagnostizierten Pneumonie waren beim Schwein nicht möglich. Es wurde jedoch eine statistisch gesicherte Beziehung zwischen dem Ausprägungsgrad der histologischen Veränderung und den sonographischen Befunden festgestellt. Der Ausprägungsgrad der histologischen Veränderung stand u.a. in direkter Beziehung zum Luftgehalt im Lungengewebe. Die Impuls-Oszilloresistometrie ist ein Verfahren zur Analyse der Atmungsmechanik und wurde am Schwein ebenfalls unter Sedation mit Diazepam (1,5 bis 2,0 mg/kg KM) oder aber nach entsprechendem Training der Tiere ohne jede medikamentelle Ruhigstellung vorgenommen. Die Schweine wurden in einer Hängematte streßarm fixiert und das Meßsystem über eine starre, luftdicht am Kopf abschließende Atemmaske an das Tier adaptiert. Insgesamt 26 Schweine wurden in die Studien zur Untersuchung verschiedener Einflüsse auf das Verhalten der IOS-Parameter einbezogen. Folgende Parameter wurden berücksichtigt: Atmungsfrequenz (Af), Atemzugvolumen (Vt), die Spektralparameter Resistance (R), Reactance (X) und Kohärenz (K) jeweils bei 5, 10, 15 und 20 Hz (R5, ...R20, X5, ...X20, K5, ...K20) sowie die Modellparameter zentrale (Rz) und periphere (Rp) Resistance, Lungencompliance (Cl) und zentrale Inertance (Lz). In einer Variabilitätsanalyse an fünf nicht sedierten, klinisch gesunden Schweinen wurde die Reproduzierbarkeit der Ergebnisse bei drei unmittelbar innerhalb weniger Minuten aufeinander folgend sowie bei an drei Tagen nacheinander zur selben Tageszeit durchgeführten IOS-Messungen überprüft. Innerhalb des kurzen Zeitraumes von wenigen Minuten wurde die Variabilität der Meßergebnisse der meisten IOS-Parameter überwiegend durch inter-individuelle Einflüsse verursacht, während bei der über mehrere Tage reichenden Betrachtungsweise der intra-individuell bedingte Anteil der Variabilität zunahm. Die Entwicklung von Alter und Körpermasse konnten im Rahmen der an elf klinisch gesunden, sedierten Schweinen über einen Zeitraum von 62 Tagen vorgenommenen IOS-Messungen nur teilweise die mit dem Wachstum einhergehenden Veränderungen der IOS-Parameter erklären. Der an acht klinisch gesunden, sedierten Schweinen festgestellte Einfluß der Tageszeit auf die IOS-Parameter war nur gering, stimmte aber von der Tendenz her mit den in der Literatur beschriebenen Angaben überein. An 16 klinisch gesunden Schweinen wurde der Einfluß der Sedation mit Diazepam auf die IOS-Parameter überprüft. Dieses Medikament führte zu einer signifikanten Verringerung von Af und Vt und zu einer Verbesserung der Qualität der IOS-Messungen (K5, K10, K20). An sieben klinisch gesunden, nicht sedierten Schweinen wurden durch Inhalation von Aerosolen mit bestimmten pharmakologisch wirksamen Substanzen (Carbachol, Fenoterolhydrobromid) definierte Zustände am respiratorischen System wie Bronchospasmus und Bronchodilatation ausgelöst und mittels IOS-Messungen nachgewiesen. Die während der bronchospastischen Reaktion vorgefundenen Veränderungen der IOS-Parameter, insbesondere der starke Anstieg der Resistance im unteren Frequenzbereich (R5), das deutliche Absinken der Reactance, insbesondere bei 5 Hz, und die beträchtliche Erhöhung des Modellparameters Rp sind für diesen Zustand des Bronchialsystems charakteristisch. Neun klinisch gesunde, sedierte Schweine wurden zunächst bei physiologischer und anschließend bei stark distal abgebeugter Kopfhaltung untersucht. Durch die starke Flexion im Kopf-Hals-Bereich wurde eine extrathorakal gelegene Obstruktion erzeugt. Hierbei waren die spektrale Resistance (R5 bis R20) und der Modellparameter Rz bei abgebeugter Kopfhaltung signifikant erhöht. Am Beispiel einer experimentell ausgelösten Infektion mit Actinobacillus pleuropneumoniae wurde der Verlauf einer respiratorischen Erkrankung an sieben sedierten Schweinen unter regelmäßiger Durchführung von IOS-Messungen, über einen Zeitraum von 23 Tagen verteilt, beobachtet. Die Resultate der IOS-Messungen 3 Tage p.i. (Resistance im gesamten Frequenzbereich erhöht, starker Anstieg von Rz und Lz ) wiederspiegelten vor allem eine Beteiligung der extrathorakal und zentral gelegenen Bereiche des Respirationstraktes. Durch die zumindest tendenziell vorhandenen Veränderungen bestimmter IOS-Parameter (Verstärkung der negativen Frequenzabhängigkeit, Erhöhung von Rp, Abnahme von Cl) wurde zusätzlich eine Beteiligung der peripheren Bereiche in der Lunge angezeigt. Für einen definierten Zeitraum wurden die IOS-Meßergebnisse den Befunden der sonographischen Untersuchung der Lunge gegenübergestellt. Dabei wurden hohe Korrelationen zwischen auf periphere Veränderungen verweisenden IOS-Parametern und sonographisch ermittelten Veränderungen an der Lunge nachgewiesen. Abschließend ist festzustellen: 1.) Beide getesteten diagnostischen Verfahren sind beim Schwein anwendbar und liefern eine wertvolle Ergänzung der konventionellen Diagnostik am Respirationstrakt dieser Tierart. 2.) Nach sonographischer Untersuchung der Lunge sind mit hoher Wahrscheinlichkeit Aussagen über das Vorhandensein pathologisch-anatomisch sichtbarer pneumonischer Verän-derungen und deren Ausdehnung im sonographisch erreichbaren Lungenfeld möglich. 3.) Die Impuls-Oszilloresistometrie liefert in einem Parameter-Komplex Informationen über den funktionellen Zustand des gesamten respiratorischen Systems. Dieser ist von zahlreichen physiologisch wirkenden Faktoren (u.a. Kopfhaltung, Wachstum, Tageszeit), applizierten pharma-kologisch wirksamen Substanzen (z.B. Diazepam, Carbachol, Fenoterolhydrobromid) und dem Vorhandensein einer Erkrankung des respiratorischen Systems (z.B. Actinobacillus pleuropneumoniae) abhängig. 4.) Da beide Verfahren verschiedene Sachverhalte, den morphologischen (Sonographie) bzw. den funktionellen Zustand (Impuls-Oszilloresistometrie) des respiratorischen Systems widerspiegeln, liefern sie einander ergänzende Aussagen. 5.) Beide diagnostischen Verfahren bieten sich beim Schwein vor allen Dingen für den Einsatz zu wissenschaftlichen Zwecken an. Aufgrund ihres nichtinvasiven Charakters ist ein schonender Umgang mit den Probanden möglich. 6.) Die Anwendung der Sonographie der Lunge ist auch in ausgewählten Fällen der tierärztlichen Praxis, z.B. beim Ankauf von Zuchttieren, denkbar.Carmen Klein: Lung Sonography and Analysis of the Respiratory Mechanics by means of Impulse Oscilloresistometry in Healthy and Pneumonic Piglets and Porkers Institute of Bacteriology and Mycology Faculty of Veterinary Medicine University of Leipzig Germany Federal Institute for Health Protection of Consumers and Veterinary Medicine Jena Branch Germany submitted in May 1999 (157 pages, 52 figures, 34 tables, 285 references, appendix with 62 pages, 15 figures, 50 tables) Two non-invasive diagnostic methods, i.e. lung sonography and impulse oscillometry, were examined for the first time with regard to their applicability and evidence in clinically healthy as well as pneumonic weaned piglets and porkers of up to ca. 50 kg b.w. A total of 45 healthy or pneumonic swine was subjected to lung sonography. For this purpose, the animals were sedated with 2.0 mg/k b.w. diazepam. Six clinically healthy swine were studied to establish the lung area accessible to sonography in this animal species. Sonography was found to cover well the cranioventral sections of the lung often affected by pneumonias. The findings established by lung sonography in the swine showed a good coincidence with results described in literature for other species. The findings in swine revealed the following picture. ? No changes: sonography NAD ? Low-grade changes: little pronounced comet-tail artefacts ? Moderate changes: Comet-tail artefacts and consolidations or echogenic basic pattern including comet-tail artifacts ? High-degree changes: basic echogenic pattern or basic echogenic pattern plus abscess or necrosis Lung sonography findings in 34 swine were assigned to the corresponding pathological-anatomical findings. Tissue considered as unchanged from the pathological-anatomical angle was found to be without or with only minor sonographic changes, with a probability (sensitivity) of 95.65 %. In tissue exhibiting pathological-anatomical changes, sonographic findings showed pictures of moderate and high-degree changes, with a probability (sensitivity) of 74.62 % A total of 49 tissue samples was subjected to histological examination. It was not possible to infer, from the sonographic findings, the type of pneumonia diagnosed histologically in the swine. Nevertheless, a statistically confirmed correlation between the degree of pronouncedness of the histological changes and the sonographic findings was established. The pronouncedness of the histological changes was, like other factors, directly related to the air content of the lung tissue. Impulse oscillometry being a method used to analyze respiratory mechanics was applied to swine either sedated by means of diazepam (1.5 - 2.0 mg/kg b.w.) or non-sedated by medication but trained correspondingly. The animals were fixed in a canvas sling with openings for the limbs, avoiding stress, and the measuring system was adapted to the animal using a rigid face mask hermetically fitting to the animal''s head. A total of 26 animals was included in the studies to examine a variety of factors influencing the IOS parameters. The following parameters were considered: Respiratory rate (Af), tidal volume (Vt), the spectral parameters resistance (R), reactance (X) and coherence (K) at 5, 10, 15 and 20 Hz each (R5, ...R20, X5, ...X20, K5, ...K20) as well as the model parameters, central (Rz) and peripheral (Rp) resistance, lung compliance (Cl) and central inertance (Lz). A variability analysis involving five non-sedated, clinically healthy swine served to examine the reproducibility of the results of three IOS measurements either performed consecutively within a few minutes, or on three consecutive days at the same time of the day. During the brief period of a few minutes, the variability of the results of measurements, for most parameters, was due to inter-individual factors while in the case of an analysis over several days, the intra-individual share of variability increased. In the context of the IOS measurements performed in eleven clinically healthy, sedated swine over a period of 62 days, development in terms of age and body weight could only partially explain the variations of the IOS parameters taking place with growth. The influence of the time of the day on IOS parameters studied in eight clinically healthy, sedated swine was found to be small; coincidence with data given in literature, however, was seen as a tendency. The influence of diazepam sedation on the IOS parameters was examined in 16 clinically healthy swine. This medication resulted in a significant reduction of Af and Vt and improved quality of IOS measurements (K5, K10, K20). In seven clinically healthy, non-sedated swine, defined respiratory situations, i.e. bronchospasm and bronchodilatation were generated by aerosol inhalation of pharmacologically active substances such as carbachol and fenoterolhydrobromide and demonstrated by IOS measurements. This state of the bronchial system is characterized by the changes in IOS parameters found at the time of the bronchospasmic reaction, in particular the vehement rise of resistance in the lower frequency range (R5), the obvious drop in reactance, especially at 5 Hz and the noteworthy rise in the model parameter, Rp. Nine clinically healthy, sedated swine were examined first with their heads in a physiological and then, in a vertical position of their heads. The severe bending in the head-neck area produced an extrathoracic obstruction. Spectral resistance (R5 - R20) and the model parameter, Rz were significantly higher at a vertical position of the head. An experimental infection of seven sedated swine with Actinobacillus pleuropneumoniae served as a model to study the course of respiratory disease. The animals were subjected to regular IOS measurements over a period of 23 days. The results of IOS measurements performed 3 days p.i. (elevated resistance over the entire frequency range, vehement rise of Rz and Lz) reflected, above all, an involvement of the extrathoracic and central areas of the respiratory tract. As a result, the modifications of defined IOS parameters (intensification of negative frequency dependency, rise in Rp, drop in Cl) which were present at least as a tendency, indicated an additional involvement of the peripheral lung areas. The results of IOS measurements over a defined period were compared with the findings from lung sonography. High correlations between IOS parameters indicating peripheral changes and lung changes detected by sonography were demonstrated. Conclusions 1.) Both diagnostic methods studied may be used in swine and will provide a valuable completion of conventional diagnosis in the respiratory tract of this species. 2.) With a high probability, lung sonography will provide evidence of the presence of visible pathological-anatomical changes in the lung and their extent in the lung area that is accessible to sonography. 3.) Impulse oscillometry provides a complex of parameters that contain information about the functional state of the entire respiratory system. This state is dependent upon numerous physiological factors (among them position of the head, growth, time of the day), pharmacologically active substances administered (e.g. diazepam, carbachol, fenoterolhydrobromide) and the presence of respiratory disease (e.g. caused by Actinobacillus pleuropneumoniae). 4.) Since the two methods reflect different facts, i.e. the morphological (sonography) and the functional (impulse oscillometry) state of the respiratory system, they supply mutually supplementing information. 5.) Both diagnostic methods offer themselves above all for use in scientific research on swine. Owing to their non-invasive character, it is possible to handle test animals in a non-offensive way. 6.) In specific cases, lung sonography may also be used in the veterinary practitioner''s surgery, e.g. for the examination of animals kept for breeding

Factorial calculation of calcium and phosphorus requirements of growing dogs

Calcium and phosphorus requirements for growing dogs can be calculated by different methods. The current standard feeding recommendations are based on experimental data derived from young giant breed puppies. In order to determine the absolute requirement, an extrapolation via metabolisable energy requirement is recommended. Another approach is to calculate the requirement factorially, taking into account the endogenous losses and the amount of calcium and phosphorus retained due to tissue accretion during growth as well as the expected availability of these nutrients. The working hypothesis was that both methods are valid and lead to comparable results in young puppies of a high mature body weight (BW). Yet, deviations for other age and mature BW groups were expected. Thus, the aim of the present study was to compare the results of both methods using exemplary puppies of different age and mature BW groups. The hypotheses could be verified for calcium. The extrapolated requirements overestimate the factorial requirements by up to 59.7% for puppies 6 months of age. In case of phosphorus requirement, the deviations between both methods are overall very high in all stages. Taking into account the potentially harmful effects of calcium and phosphorus excess, the feeding recommendations based on the extrapolation should be reconsidered

Changes in ventilation distribution in children with neuromuscular disease using the insufflator/exsufflator technique: an observational study.

Patients with neuromuscular disease often suffer from weak and ineffective cough resulting in mucus retention and increased risk for chest infections. Different airway clearance techniques have been proposed, one of them being the insufflator/exsufflator technique. So far, the immediate physiological effects of the insufflator/exsufflator technique on ventilation distribution and lung volumes are not known. We aimed to describe the immediate effects of the insufflator/exsufflator technique on different lung volumes, forced flows and ventilation distribution. Eight subjects (age 5.8-15.2 years) performed lung function tests including spirometry, multiple breath washout and electrical impedance tomography before and after a regular a chest physiotherapy session with an insufflator/exsufflator device. Forced lung volumes and flows as well as parameters of ventilation distribution derived from multiple breath washout and electrical impedance tomography were compared to assess the short-term effect of the therapy. In this small group of stable paediatric subjects with neuromuscular disease we could not demonstrate any short-term effects of insufflation/exsufflation manoeuvres on lung volumes, expiratory flows and ventilation distribution. With the currently used protocol of the insufflation/exsufflation manoeuvre, we cannot demonstrate any immediate changes in lung function

Complications arising from aesthetic surgery procedures in foreign countries and Switzerland

BACKGROUND: Cosmetic surgery tourism has increased in popularity in recent years, with arising complications and post-operative follow-up care often managed in the client's home country, thereby burdening the Swiss health care system. METHODS: We retrospectively reviewed patients with complications after cosmetic surgeries abroad and in Switzerland who were treated at the University Hospital Zurich between 2015 and 2019. Data were collected from medical records and reviewed for patient characteristics, procedures, complications, and treatment modalities. RESULTS: A total of 228 patients (207 females and 21 males) were identified with female mean age of 40.9±12.0 years and male mean age of 34.3±8.9 years. Most complications were observed for procedures performed in Europe (69%) with only thirty-six patients (16%) experiencing complications due to a procedure undertaken in Switzerland. Breast surgery was the most frequently performed procedure (60%), followed by body contouring (17%) and facial surgery (12%). The most common complications occurring after surgeries abroad were pain and discomfort (19%) as well as aesthetic dissatisfaction (18%), followed by wound breakdown (14%) and infection (11%). Most patients (76%) were treated as outpatients and the treatment of all patients over the observed period cost the healthcare system $ 795,574. CONCLUSIONS: There is an ongoing trend of cosmetic surgery tourism leading to an increasing number of patients with complications requiring aftercare in Switzerland. In contrast to previous research, more men are seeking cosmetic surgery abroad and the most common complications, such as wound healing disorders and infection, descreased in favor of aethetic dissatisfaction, possibly indicating ameliorated patient aftercare abroad

Imaging Spin Reorientation Transitions in Consecutive Atomic Co layers

By means of spin-polarized low-energy electron microscopy (SPLEEM) we show that the magnetic easy-axis of one to three atomic-layer thick cobalt films on ruthenium crystals changes its orientation twice during deposition: one-monolayer and three-monolayer thick films are magnetized in-plane, while two-monolayer films are magnetized out-of-plane, with a Curie temperature well above room temperature. Fully-relativistic calculations based on the Screened Korringa-Kohn-Rostoker (SKKR) method demonstrate that only for two-monolayer cobalt films the interplay between strain, surface and interface effects leads to perpendicular magnetization.Comment: 5 pages, 4 figures. Presented at the 2005 ECOSS conference in Berlin, and at the 2005 Fall meeting of the MRS. Accepted for publication at Phys. Rev. Lett., after minor change

Portrait d’initiatives québécoises de recherche ayant utilisé une méthode dite d’enquête citoyenne

Ce rapport de recherche présente, dans un premier temps, un cadre de réflexion propice à la réalisation d’activités de recherche qui reposent sur une mobilisation de connaissances détenues par la population d’un territoire local. Dans un deuxième temps, cinq expériences de collecte de données impliquant une participation citoyenne sont présentées. Deux de ces expériences illustrent des démarches ayant pour objectif de mobiliser des citoyennes. Les trois autres sont des exemples où la collecte d’informations détenues par la population locale est vue comme un plus pour définir des projets qui soient mieux ancrés dans leur communauté

Comparison of Veterinary Nutrition Exam Results After Classroom or Virtual Teaching During the COVID-19 Pandemic at a German University

Due to the COVID-19 pandemic, university teaching had to be kept up in spite of severe contact restrictions. Virtual teaching of animal nutrition was implemented at the Veterinary Faculty of the Ludwig-Maximilians-Universität (LMU) München, Germany, for both lectures and practical courses. Live online classes were held via Zoom®, and recordings were accessible afterwards. Animal nutrition is taught in the 5th and 6th term of the veterinary studies, followed by an oral state exam about subjects from both terms. In this study, the success of classroom vs. virtual teaching in veterinary animal nutrition was evaluated by comparison of exam results. Two exam cohorts (2019, before the pandemic; 2020, with one term of virtual teaching during the pandemic) were evaluated. The results indicated no significant difference of teaching method on the grades. However, there was a significantly higher probability of students not taking or failing the exam in the 2020 exam cohort, suggesting a general effect of the pandemic on the students. Additionally, two surveys were distributed among the students during summer term 2020 and winter term 2020/21, when virtual teaching due to the pandemic had been implemented for the first time. The survey results provide insights into the students' view of benefits and problems of virtual teaching in animal nutrition at the LMU. The majority was in favor of the live online format for lectures and courses in computed-based ration calculation, whilst feedstuff demonstrations were preferred in classroom setting

A successful approach to conrol burning mouth syndrome using matricaria recutita and cognitive therapy

The burning mouth syndrome (BMS) has no specific clinical and laboratory signs. Its etiology is yet to be elucidated, but it is considered to be affected by multifactorial, psychological, and local and systemic factors. This condition is considered of great morbidity, and the main complaint of patients maybe associated with xerostomia, thirst, and altered taste. The present study aims to report two cases of BMS and to evaluate the outcome of cognitive therapy (CT) plus phytotherapy in the control of BMS. The patients were female, Caucasian, and aged between 58 and 69 years. The most BMS-affected anatomical parts were the lips and the tongue. In the clinical approach, oral and systemic evaluation, and disease management with CT plus chamomile tea were done. The patients were reassured, and their response to therapy one year after was found to be excellent despite few exacerbations in periods of great emotional stress. Thus, we conclude that psychological treatment is vital in the management of BMS, as CT, along with Matricaria recutita phytotherapy, displayed excellent results in the control of BMS

Metabolisable energy intake and growth of privately owned growing dogs in comparison with official recommendations on the growth curve and energy supply

The correct assumption of metabolisable energy (ME) requirement is essential for the nutrition consultation and diet formulation. In young dogs, too high energy supply can accelerate growth and thus lead to developmental orthopaedic diseases. The aim of the present study was to collect the data on ME intake and body weight (BW) development in privately owned growing dogs in order to compare these data with the current recommendations. Our hypothesis was that the actual ME intake of healthy young dogs would be lower than the actual recommendation. The data of 493 privately owned puppies (median age at first consultation 21 weeks, the median expected mature BW 30 kg) on ME intake, actual and expected mature BW were collected and compared with recommendations of the Society of Nutrition Physiology (GfE, Meyer and Zentek and NRC). In 243 dogs, there was a follow‐up. The actual BW did not deviate systematically from the calculated expected BW (R2 = .929). The ME intake significantly decreased with age (p .05). Sex had no effect on the ME intake (p > .05). The ME intake of young dogs with a history of skeletal problems or of food allergy did not differ systematically from healthy dogs of similar age and expected mature BW. The ME intake was considerably below NRC recommendations, especially in younger puppies (>8–17 weeks: 78%, >17–26 weeks: 83% of NRC recommendation). A predictive linear equation for ME intake was developed: ME intake (MJ) = (1.063 − 0.565 × [actual BW/expected mature BW]) × actual BW0.75

Overcoming hypoxia-induced tumor radioresistance in non-small cell lung cancer by targeting DNA-dependent protein kinase in combination with carbon ion irradiation

Background: Hypoxia-induced radioresistance constitutes a major obstacle for a curative treatment of cancer. The aim of this study was to investigate effects of photon and carbon ion irradiation in combination with inhibitors of DNA-Damage Response (DDR) on tumor cell radiosensitivity under hypoxic conditions. Methods: Human non-small cell lung cancer (NSCLC) models, A549 and H1437, were irradiated with dose series of photon and carbon ions under hypoxia (1% O2) vs. normoxic conditions (21% O2). Clonogenic survival was studied after dual combinations of radiotherapy with inhibitors of DNA-dependent Protein Kinase (DNAPKi, M3814) and ATM serine/threonine kinase (ATMi). Results: The OER at 30% survival for photon irradiation of A549 cells was 1.4. The maximal oxygen effect measured as survival ratio was 2.34 at 8 Gy photon irradiation of A549 cells. In contrast, no significant oxygen effect was found after carbon ion irradiation. Accordingly, the relative effect of 6 Gy carbon ions was determined as 3.8 under normoxia and. 4.11 under hypoxia. ATM and DNA-PK inhibitors dose dependently sensitized tumor cells for both radiation qualities. For 100 nM DNAPKi the survival ratio at 4 Gy more than doubled from 1.59 under normoxia to 3.3 under hypoxia revealing a strong radiosensitizing effect under hypoxic conditions. In contrast, this ratio only moderately increased after photon irradiation and ATMi under hypoxia. The most effective treatment was combined carbon ion irradiation and DNA damage repair inhibition. Conclusions: Carbon ions efficiently eradicate hypoxic tumor cells. Both, ATMi and DNAPKi elicit radiosensitizing effects. DNAPKi preferentially sensitizes hypoxic cells to radiotherapy