Phaidra - University of Veterinary Medicine Vienna
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Beyond symptomatic alignment: evaluating the integration of causal mechanisms in matching animal models with human pathotypes in osteoarthritis research
No full textOsteoarthritis (OA) is a highly prevalent and disabling condition lacking curative treatments, with only symptomatic relief available. Recognizing OA as a heterogenous disorder with diverse aetiologies and molecular foundations underscores the need to classify patients by both phenotypes and molecular pathomechanisms (endotypes). Such stratification could enable the development of targeted therapies to surmount existing treatment barriers. From a scientific, economic, and ethical perspective, it is crucial to employ animal models that accurately represent the endotype of the target patient population, not merely their clinical symptoms. These models must also account for intrinsic and extrinsic factors, like age, sex, metabolic status, and comorbidities, which impact OA\u27s pathogenesis and its clinical and molecular variability and can profoundly influence not only structural and symptomatic disease severity and progression but also the underlying molecular pathophysiology. The molecular definition of the OA subpopulation must also be reflected in the read-outs, as the traditional methods-macroscopic and histological scoring, along with limited gene expression profiling of established biomarkers for cartilage degradation, extracellular matrix (ECM) turnover, and synovial inflammation-are inadequate for discovering new, phenotype- and endotype-specific biomarkers or therapeutic targets. Thus, animal model characterisation should evolve to include both clinically and pathophysiologically pertinent measures of disease progression and response to treatment. This review evaluates the utility and accuracy of current animal models in OA research, focusing on their capacity to replicate the disease\u27s pathophysiological processes
A first glimpse into circulating ghrelin patterns of thin-billed prion chicks (Pachyptila belcheri)
No full textThe peptide hormone ghrelin, also known as "hunger hormone", is primarily secreted by the stomach and plays a key role in the regulation of vertebrate appetite and energy balance. While the hunger hormone and its functions have been extensively researched in mammalian species, its physiological roles have received less attention in birds and knowledge on the ghrelin system is especially poor in wild avian species. In contrast to mammals, ghrelin acts as an anorexigenic signal in birds and suppresses food intake. In this study, we focussed on the altricial chicks of thin-billed prions (Pachyptila belcheri) which are subjected to irregular, up to 8 day-long fasts, while waiting for their parents to return from feeding trips. We show that thin-billed prion chicks, which received a meal in the night prior to sampling, had higher circulating ghrelin levels than fasting conspecifics. Ghrelin levels did not correlate with chick body condition, meal size, or the length of a fast. Our study adds to past literature supporting an anorexigenic effect of avian ghrelin and is among the first to describe ghrelin profiles in seabirds, thereby significantly contributing to the scarce literature on ghrelin in wild avian species
Application of NanoScope in Treating Severe Shoulder Dysplasia With Intraarticular Osseous Bodies in a Cat
No full textA 2-year and 9-month-old male neutered Himalayan cat was evaluated for lameness of the left thoracic limb. Orthopaedic examination and radiography revealed severe bilateral shoulder joint dysplasia and intraarticular osseous bodies. The lameness was resolved after successful removal of two intraarticular bodies from the left shoulder joint using a needle-sized chip-on-tip technology arthroscope (NanoScope). Histology of these two bodies showed enchondral ossification. Nine months after surgery, radiographs showed a new osseous body at the same location as before, and a gait analysis using a pressure plate revealed mild lameness, which was not detectable in orthopaedic examination
Studying the Impact of the DDB2 T338M Missense Mutation on the Development of Equine Squamous Cell Carcinoma and Sarcoid
No full textA missense mutation in damage-specific DNA binding protein 2 (DDB2 c.1013 C>T; p.Thr338Met) has been described as a risk factor for ocular squamous cell carcinoma (OSCC) in the Haflinger breed. Here, we examined the impact of DDB2 C>T allele status on the development of OSCC, squamous cell carcinoma (SCC) at other localisations, or equine sarcoid (ES) in Haflingers and other breeds with a high incidence of these tumour types. We genotyped affected Haflinger, Noriker, Warmblood, and Icelandic horses. Results based on 56 Haflingers confirmed the significantly higher risk for OSCC in DDB2-TT Haflingers but also suggested an increased risk in heterozygous (DDB2-CT) Haflingers. We also found the DDB2-T allele in Norikers with OSCC but not in Warmbloods. Only one homozygous DDB2-T allele carrier was among the 23 Haflinger and 44 Noriker/Warmblood/Icelandic horses with an SCC at a localisation other than the eye or ES. Overall, our data underline the severity of the DDB2-T allele with regard to OSCC and provide no evidence for the impact of the DDB2 risk allele status on the development of ES and SCC at localisations other than the eye
Deciphering the code of resistance: a genomic and transcriptomic exploration of the Cystoisospora suis Holland-I strain
No full textCystoisospora suis, a member of the apicomplexan order Coccidia and causative agent of neonatal porcine coccidiosis, poses a challenge to pig production due to the emergence of reduced efficacy of toltrazuril, the only EU-approved treatment. To address the critical gaps in understanding toltrazuril resistance and possibilities of early diagnostics, our study investigated the genetic basis of resistance through whole-genome DNA sequencing and transcriptome analysis of two C. suis strains, the toltrazuril-susceptible Wien-I and the resistant Holland-I. Additionally, we studied the mitochondrial genome and analysed mitochondrial gene expression in both strains. Our results show that genes encoding proteins involved in host-cell invasion displayed variable expression patterns and genetic mutations, suggesting adaptive changes in invasion mechanisms. Moreover, substantial fluctuations in the expression of genes linked to retrotransposons, accompanied by genetic alterations, were observed, highlighting their potential involvement in genomic rearrangements. Finally, our mitochondrial genome analyses revealed important insights into its genetic organization and conservation. Notably, the marked downregulation of CoI, CoIII and Cytb mRNA levels in the resistant strain Holland-I upon toltrazuril exposure highlights the dynamic response of mitochondrial genes to toltrazuril. These mitochondrial adaptations appear to be closely linked to the parasite drug resistance mechanism, potentially facilitating its survival under pharmacological stress. These findings enhance our knowledge of drug resistance mechanisms in Coccidia and highlight the need for novel management strategies, leading to the development of targeted treatments and controls
Improvement in the Usability of Meat Inspection Findings for Swine Herd Health Management
No full textData from post-mortem inspections conducted using official controls on the meat production of slaughtered pigs are generally considered valuable for identifying herd health issues and ensuring meat safety. However, several studies highlighted that a multi-stage assessment of lung changes would provide more useful information on animal health than the implemented binary (yes/no) recording. For this purpose, a new scheme was developed and subsequently used by trained official veterinarians at four slaughterhouses in Austria. Implementation of the multi-stage assessment was carried out in parallel with the conventional assessment, and data collected from both schemes were analyzed and compared to evaluate effectiveness. The analysis of the data (n = 20,345) showed that the most common alteration was low-grade (28.4%), followed by moderate-grade (11.3%,) and then high-grade pneumonia (5.2%). In the case of pleurisy, 88.9% of the carcasses showed no alterations of the pleura, and 11.1% had pathological changes (low-grade pleurisy = 4.7%, moderate-grade pleurisy = 2.7%, high-grade pleurisy = 3.7%). Analysis of the results showed a strong heterogeneity of the frequency of alterations between the batches reflecting various underlying animal health issues. Among the influencing factors, the origin of the pigs had the greatest influence. The project demonstrated that the new evaluation can be carried out easily with no extra time effort once staff are trained and the technological platform for reporting is adapted. The more detailed information ensures more useful feedback is provided to the farmers and supervising veterinarians, thereby ensuing animal welfare and contributing to sustainable, improved animal husbandry
Septic tendosynovitis in a breeding ram and isolation of Mycoplasma arginini
No full textA breeding ram was submitted to a veterinary hospital due to persistent pneumonia, emaciation and high fever. Upon submission, it also showed severe weight-bearing lameness on all four legs with highly fluid-filled digital flexor tendon sheaths. Additionally, a mild brisket sore was diagnosed. The postmortem examination revealed a chronically active fibrinosuppurative inflammation of the digital flexor tendon sheaths on all four legs. Additionally, a distinctive chronically active necrotising, suppurative and abscess-forming soft tissue inflammation was identified in the sternal area. Microbiological examination of tissue samples from different locations revealed a mixed bacterial colonisation including Escherichia coli, Klebsiella oxytoca and Trueperella pyogenes. Additionally, Mycoplasma arginini was detected in samples of the lung and tendon sheaths. Genome sequencing and characterisation of M. arginini revealed the presence of a prophage associated with arthritogenesis in related Mycoplasma species. However, the contribution of M. arginini to the diagnosed tendosynovitis cannot be conclusively clarified
Variations in extracellular vesicle shedding of Cystoisospora suis stages (Apicomplexa: Coccidia)
No full textCystoisospora suis, a porcine enteral parasite of the order Coccidia, is characterized by a complex life cycle, with asexual and sexual development in the epithelium of the host gut and an environmental phase as an oocyst. All developmental stages vary greatly in their morphology and function, and therefore excrete different bioactive molecules for intercellular communication. Due to their complex development, we hypothesized that the extracellular vesicles (EVs) cargo is highly dependent on the life cycle stages from which they are released. This study aimed to characterize and compare EVs of all developmental stages of C. suis. Nanoparticle tracking analysis and microscopy were used to determine particle numbers and size distributions of stage-specific parasite EVs. Furthermore, Fourier-transform infrared spectral analysis was employed for the metabolic fingerprinting of EVs, and the lipid and protein profiles of all parasite stages were determined. Overall, the study revealed that asexual, sexual and transmissible stages of C. suis release different EVs during the parasite\u27s life cycle. EVs of endogenous asexual and sexual stages were found to be more similar to each other than to those of the transmissible environmental stage, the oocyst. Furthermore, the ratio of fatty acids to polysaccharides and proteins changed during parasite development. In particular, proteins associated with the Apicomplexa and those involved in vesicle shedding showed changes in expression in all parasite stages. Lipid analysis showed that fatty acids were found in the same concentration through all parasite stages, whereas the amount of stereolipids, sphingolipids and glycerolipids changed between the parasite stages. In conclusion, this study, which presents the first known characterization of C. suis EVs, demonstrates a link between EVs and the respective developmental stages of the parasite, and putative functions in the parasite-parasite and host-parasite interplays
Osteosarcoma Cells and Undifferentiated Human Mesenchymal Stromal Cells Are More Susceptible to Ferroptosis than Differentiated Human Mesenchymal Stromal Cells
No full textCurrent research suggests that promoting ferroptosis, a non-apoptotic form of cell death, may be an effective therapy for osteosarcoma, while its inhibition could facilitate bone regeneration and prevent osteoporosis. Our objective was to investigate whether the susceptibility to and regulation of ferroptosis differ between undifferentiated (UBC) and differentiated (DBC) human bone marrow stromal cells, as well as human osteosarcoma cells (MG63). Ferroptosis was induced by either inhibiting glutathione peroxidase 4 (GPX4) using RSL3 or blocking all glutathione-dependent enzymes through inhibition of the glutamate/cysteine antiporter with Erastin. Lipid peroxidation was assessed using the fluorescent probe BODIPY™581/591C11, while Ferrostatin-1 was used to inhibit ferroptosis. We demonstrate that neither Erastin nor RSL3 induces ferroptosis in DBC. However, both RSL3 and Erastin induce ferroptosis in UBC, while Erastin predominantly induces ferroptosis in MG63 cells. Our data suggest that ferroptosis induction in undifferentiated hBMSCs is primarily regulated by GPX4, whereas glutathione S-Transferase P1 (GSTP1) plays a key role in controlling ferroptosis in osteosarcoma cells. In conclusion, targeting the key pathways involved in ferroptosis across different bone cell types may improve the efficacy of cancer treatments while minimizing collateral damage and supporting regenerative processes, with minimal impact on cancer therapy
Herbicide glyphosate efficiently inhibits growth of pathogenic Prototheca algae species, suggesting the presence of novel pathways for the development of anti-algal drugs
No full textPrototheca are ubiquitous algae and occasional pathogens of humans and animals. While rare, the infection is often fatal and treatment options are limited to antifungals with low efficiency. Here, using growth curve assays, we demonstrate that five pathogenic species of Prototheca (P. blaschkeae, P. wickerhamii, P. cutis, P. ciferrii, P. bovis) were fully inhibited by 50–100 μg/mL of herbicide glyphosate, suggesting novel pathways that can be considered for anti-algal drug development