semi-minimal-invasive-method-to-induce-myocardial-infarction-rats

Semi-Minimal Invasive Method to Induce Myocardial Infarction in Rats and the Assessment of Cardiac Function by an Isolated Working Heart System

Myocardial infarction (MI) remains the main contributor to morbidity and mortality worldwide. Therefore, research on this topic is mandatory. An easily ...

determination-vaccine-immunogenicity-using-bovine-monocyte-derived

Determination of Vaccine Immunogenicity Using Bovine Monocyte-Derived Dendritic Cells

Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs) within the immune system. They patrol the organism looking for pathogens and ...

Vetmeduni Vienna

University of Veterinary Medicine, Vienna

The objectives of this study were to characterize clinical, intrauterine, bacteriologic and cytologic changes during the first month after parturition in healthy dairy cows and in cows with subclinical endometritis (SE) or clinical endometritis (CE). Furthermore, risk factors related to clinical bacteriologic and cytologic findings were determined. A total of 170 calvings were enrolled, and intrauterine samples were collected on Days 0, 3, 9, 15, 21, and 28 postpartum using the cytobrush technique. The presence of Escherichia coli and Trueperella pyogenes was determined by Fourier transform infrared spectroscopy. The cows were categorized according to their uterine health status (UHS) on Day 21 as healthy (clear or absent vaginal discharge and <5% polymorphonuclear cells [PMN] in the cytologic sample), SE (clear or absent vaginal discharge and ≥5% PMN), or CE (vaginal mucus containing any signs of pus). The prevalence of SE and CE on Day 21 was 27.9% and 58.4%, respectively. Generally, samples from cows with SE and CE showed a greater bacterial growth density (BGD) than those from healthy cows. The BGD tended to be affected by the interaction of time by UHS (P = 0.057). Differences between healthy, SE, and CE cows were found from Day 3 to the last sampling day. Furthermore, the percentage of PMN differed between healthy, SE, and CE cows and was affected by time in a cubic way (decrease/increase/decrease). Overall, E coli was found in 25.4% of the samples, and T pyogenes was identified in 30.2% of the samples. The risk for CE was increased by BGD and the presence of T pyogenes. Conversely, the presence of E coli had no effect on the risk of CE or the risk of SE. The risk for an infection with T pyogenes was greater in the first-parity cows and in cows with assisted calving. In conclusion, changes in BGD and proportion of PMN varied with the UHS (healthy, SE, and CE), which was affected by the presence of T pyogenes but not E coli.

Dynamics of bacteriologic and cytologic changes in the uterus of postpartum dairy cows.

Sheep are one of the most frequently used large animal models in stem cell research. However, minimal invasive or noninvasive sources of mesenchymal stem cells (MSCs) in sheep are scarce. In the light of the principles of the 3Rs (reduce, refine, replace), it would therefore be desirable to identify a minimally invasive or noninvasive ovine MSC source. In humans, the chorionic villi of the placenta, which can be noninvasively harvested as part of the afterbirth, have been identified as a rich source of MSCs. Therefore, in the present study, ovine placenta cotyledons, which have similar function and structure to human chorionic villi, were tested for their potential use as a noninvasive source of ovine MSCs. Through mincing of the placental cotyledons, collagenase digestion, and Ficoll density gradient centrifugation, combined with plastic adherence selection, MSCs were successfully isolated. Their morphological, immunophenotypical, and cellular growth characteristics, as well as their proliferation, differentiation, and migration potential, were evaluated and compared to the currently best-researched MSC source, bone marrow-derived stem cells. Ovine cotyledons were shown to be a reliable, abundant source for the noninvasive, pain- and risk-free harvest of MSCs. The collection procedure does not interfere with partum or the initial bonding phase between ewes and lambs and is therefore exempt from ethical debate. Ovine placenta cotyledon-derived MSCs exhibit multipotential characteristics and can be cryopreserved for later use.

Sheep Placenta Cotyledons: A Noninvasive Source of Ovine Mesenchymal Stem Cells.

Fetal unilateral ureteral obstruction (UUO) triggers complex pathophysiology involving not only the affected organ but also the contralateral kidney, which undergoes evident compensatory changes.

A fetal sheep model for studying compensatory mechanisms in the healthy contralateral kidney after unilateral ureteral obstruction.

Osteoarthritis (OA), a degenerative joint disease characterized by progressive cartilage degeneration, is one of the leading causes of disability worldwide owing to the limited regenerative capacity of adult articular cartilage. Currently, there are no disease-modifying pharmacological or surgical therapies for OA. Fetal mammals, in contrast to adults, are capable of regenerating injured cartilage in the first two trimesters of gestation. A deeper understanding of the properties intrinsic to the response of fetal tissue to injury would allow us to modulate the way in which adult tissue responds to injury. In this study, we employed secretome proteomics to compare fetal and adult protein regulation in response to cartilage injury using an ovine cartilage defect model. The most relevant events comprised proteins associated with the immune response and inflammation, proteins specific for cartilage tissue and cartilage development, and proteins involved in cell growth and proliferation. Alarmins S100A8, S100A9 and S100A12 and coiled-coil domain containing 88A (CCDC88A), which are associated with inflammatory processes, were found to be significantly upregulated following injury in adult, but not in fetal animals. By contrast, cartilage-specific proteins like proteoglycan 4 were upregulated in response to injury only in fetal sheep postinjury. Our results demonstrate the power and relevance of the ovine fetal cartilage regeneration model presented here for the first time. The identification of previously unrecognized modulatory proteins that plausibly affect the healing process holds great promise for potential therapeutic interventions.

Fetal articular cartilage regeneration versus adult fibrocartilaginous repair: secretome proteomics unravels molecular mechanisms in an ovine model.

Currently, subclinical metabolic imbalances at the individual cow and herd level are detected by measuring biomarkers in single blood samples. However, diurnal variations have not been fully described yet but need to be considered when sampling for a robust ad consistent analysis. The study describes the influence of lactation phases on circadian rhythms and diurnal variations for non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHB), total bilirubin (tBIL) and aspartate aminotransferase (AST) in dairy cows. In an observational pilot study, we used 16 clinically healthy Simmental dairy cows subdivided in four different lactation stages (dry-off, fresh, high and late lactating). Every cow was monitored for 24 h, with blood sampling and assessment of clinical parameters every 2 h. Time and lactation stage influence the concentration of the biomarkers NEFA, BHB and tBIL in serum. Further, circadian rhythmicity was found in high lactating cows for NEFA peaking at 5:39 am and BHB peaking at 4:20 pm. We suggest blood sampling for single-point measurements within three hours after the first feeding until two hours after the last feeding of the day. The results provide a new insight into the physiology of circadian rhythms in dairy cows and enable improved metabolic monitoring.

Influence of Different Lactation Stages on Circadian Rhythmicity of Metabolic Biomarkers in Dairy Cows: A Pilot Study.

Currently about 30% to 50% of all dairy cows are affected by a metabolic or infectious disease during the transition period. A key factor for preventive actions is the ability to precisely predict metabolic diseases at an early stage. We report the longitudinal metabolic profile of non-esterified fatty acids, beta-hydroxybutyrate (BHB), total bilirubin, and aspartate aminotransferase in hyperketonemic dairy cows. Aiming for a novel measurement regime to improve metabolic health in dairy cows, we evaluated prognostic classifiers for hyperketonemia. In the observational longitudinal study, 99 healthy adult primiparous and multiparous Simmental dairy cows were included. Every cow was monitored weekly for 14 consecutive weeks, beginning two weeks prior to the expected day of parturition until peak lactation. Cows with serum concentrations of BHB > 0.8 mmol/L were considered hyperketonemic. Biomarker profiles were fitted by the maximum likelihood method using a mixed effects natural cubic spline model. In the hyperketonemic group, the BHB profile remained significantly higher than that of the control group until the end of the study period. As a prognostic classifier, the cut-off level of 0.54 mmol/L BHB measured on the 10th day post partum had the highest area under the curve. These results provide new longitudinal insights into the metabolic biomarker progression of dairy cows and enable an early onset diagnosis of hyperketonemia.

Longitudinal Metabolic Biomarker Profile of Hyperketonemic Cows from Dry-Off to Peak Lactation and Identification of Prognostic Classifiers.

Tendinopathies are painful, disabling conditions that afflict 25% of the adult human population. Filling an unmet need for realistic large-animal models, we here present an ovine model of tendon injury for the comparative study of adult scarring repair and fetal regeneration. Complete regeneration of the fetal tendon within 28 days is demonstrated, while adult tendon defects remained macroscopically and histologically evident five months post-injury. In addition to a comprehensive histological assessment, proteome analyses of secretomes were performed. Confirming histological data, a specific and pronounced inflammation accompanied by activation of neutrophils in adult tendon defects was observed, corroborated by the significant up-regulation of pro-inflammatory factors, neutrophil attracting chemokines, the release of potentially tissue-damaging antimicrobial and extracellular matrix-degrading enzymes, and a response to oxidative stress. In contrast, secreted proteins of injured fetal tendons included proteins initiating the resolution of inflammation or promoting functional extracellular matrix production. These results demonstrate the power and relevance of our novel ovine fetal tendon regeneration model, which thus promises to accelerate research in the field. First insights from the model already support our molecular understanding of successful fetal tendon healing processes and may guide improved therapeutic strategies.

Molecular Mechanisms of Fetal Tendon Regeneration Versus Adult Fibrous Repair.

This study aimed to evaluate the effects of diet-induced subacute rumen acidosis (SARA) severity during transition and the early lactation period on claw health in 24 first-lactation Holstein heifers. All heifers were fed a 30% concentrate (in dry matter) close-up ration three weeks before calving, then switched to a high-concentrate ration (60% dry matter), which was fed until the 70th day in milk (DIM) to induce SARA. Thereafter, all cows were fed the same post-SARA ration with around 36% concentrate in dry matter. Hoof trimming was performed before calving (visit 1), at 70 (visit 2) and at 160 DIM (visit 3). All claw lesions were recorded, and a Cow Claw Score (CCS) was calculated for each cow. Locomotion scores (LCS 1-5) were assessed at two-week intervals. Intraruminal sensors for continuous pH measurements were used to determine SARA (pH below 5.8 for more than 330 min in 24 h). The cluster analysis grouped the cows retrospectively into light (≤11%;  = 9), moderate (>11-<30%;  = 7), and severe (>30%;  = 8) SARA groups, based on the percentage of days individual cows experienced SARA. Statistically significant differences were found between SARA groups light and severe in terms of lameness incidence ( = 0.023), but not for LCS and claw lesion prevalence. Further, the analysis of maximum likelihood estimates revealed that for each day experiencing SARA, the likelihood of becoming lame increased by 2.52% ( = 0.0257). A significant increase in white line lesion prevalence was observed between visits 2 and 3 in the severe SARA group. The mean CCS in severe SARA group cows were higher at each visit compared to cows in the other two groups, but without statistical significance. Overall, this is the first study indicating that first-lactation cows fed a similar high-concentrate diet but with a higher severity of SARA tended to have poorer claw health, albeit with only partial statistical evidence.

ArticleTotal : 2	Year
Publication title Cited by 5	2020
Publication title Cited by 1	2023

Article	Year
Dynamics of bacteriologic and cytologic changes in the uterus of postpartum dairy cows. Theriogenology\| PubMed ID: 25270027	2014
Sheep Placenta Cotyledons: A Noninvasive Source of Ovine Mesenchymal Stem Cells. Tissue engineering. Part C, Methods\| PubMed ID: 28504918	2017
A fetal sheep model for studying compensatory mechanisms in the healthy contralateral kidney after unilateral ureteral obstruction. Journal of pediatric urology\| PubMed ID: 26211402	2015
Fetal articular cartilage regeneration versus adult fibrocartilaginous repair: secretome proteomics unravels molecular mechanisms in an ovine model. Disease models & mechanisms\| PubMed ID: 29991479	2018
Influence of Different Lactation Stages on Circadian Rhythmicity of Metabolic Biomarkers in Dairy Cows: A Pilot Study. Animals : an open access journal from MDPI\| PubMed ID: 33917264	2021
Longitudinal Metabolic Biomarker Profile of Hyperketonemic Cows from Dry-Off to Peak Lactation and Identification of Prognostic Classifiers. Animals : an open access journal from MDPI\| PubMed ID: 34068648	2021
Molecular Mechanisms of Fetal Tendon Regeneration Versus Adult Fibrous Repair. International journal of molecular sciences\| PubMed ID: 34070692	2021
Effects of High Concentrate-Induced Subacute Ruminal Acidosis Severity on Claw Health in First-Lactation Holstein Cows. Animals : an open access journal from MDPI\| PubMed ID: 37106981	2023

Johann Huber

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