Population Pharmacokinetic Modeling of Amoxicillin in Plasma and Milk in Lactating Göttingen Minipigs - A Contribution from the ConcePTION Project.

Background: Amoxicillin is frequently prescribed to peripartum women as prophylaxis and treatment for infection. Despite frequent usage of amoxicillin in lactating women, quantitative evidence regarding its transfer between systemic circulation and breastmilk remains limited. However, such data is fundamentally essential for assessing the safety risk of medicine usage during breastfeeding.

Milt androgen profile and evaluation of sperm morpho-functional characteristics of wild-caught and farmed European eels (Anguilla anguilla).

Evaluating milt samples before their preservation and/or reproductive use is critical to correctly develop assisted reproductive strategies for teleost species. This is especially true in case of "critically endangered" species, like the European eel (Anguilla anguilla), whose life cycle is not closed yet, leading to the necessity of capturing younglings from natural populations for both research and productive purposes. Despite androgens being involved in spermatogenesis and playing pivotal roles in the pre-migratory morphological and physiological changes, their quantification in different biological tissues is still to be refined in European eels.

Retinal gene therapy for Stargardt disease with dual AAV intein vectors is both safe and effective in large animal models.

Retinal gene therapy using dual adeno-associated viral (AAV) intein vectors can be applied to genetic forms of blindness caused by mutations in genes with coding sequences that exceed single AAV cargo capacity, such as Stargardt disease (STGD1), the most common inherited macular dystrophy. In view of clinical translation of dual AAV intein vectors, here we set to evaluate both the efficiency and safety of their subretinal administration in relevant large animal models. Accordingly, we have developed the first pig model of STGD1, which we found to accumulate lipofuscin similarly to patients.

Comparison of hair steroid levels among Wistar rats exposed to different environmental enrichment settings.

Background And Aim: Environmental enrichment (EE) is a pivotal tool for creating ideal housing conditions that allow animals to fully display their ethograms. At the micro-environmental level, they should elicit cognitive and social responses and increase physical activities. Hair steroids may be among the best biomarkers to evaluate the effects of prolonged exposure to different enrichments because they are non-invasive and provide information regarding a longer period.

Göttingen Minipigs as a Model for Assessing the Impact of Drugs on the Gut and Milk Microbiota-A Preliminary Study.

Background: Early gut microbiota (GM) dysbiosis can affect a child's health and has been linked to the onset of pathologies later in life. Breast milk is recognized as a major driver of the structure and dynamics of an infant's GM. In addition to nutritious and prebiotic compounds, milk contains a microbiota that is shaped by several maternal factors, including gut microorganisms and medications.

Protective effects of mesenchymal stem cells-derived extracellular vesicles against ischemia-reperfusion injury of hearts donated after circulatory death: Preliminary study in a pig model.

Introduction: Insufficient supply of cardiac grafts represents a severe obstacle in heart transplantation. Donation after Circulatory Death (DCD), in addition to conventional donation after brain death, is one promising option to overcome the organ shortage. However, DCD organs undergo an inevitable more extended period of warm unprotected ischemia between circulatory arrest and graft procurement.

Origami-inspired soft fluidic actuation for minimally invasive large-area electrocorticography.

Electrocorticography is an established neural interfacing technique wherein an array of electrodes enables large-area recording from the cortical surface. Electrocorticography is commonly used for seizure mapping however the implantation of large-area electrocorticography arrays is a highly invasive procedure, requiring a craniotomy larger than the implant area to place the device. In this work, flexible thin-film electrode arrays are combined with concepts from soft robotics, to realize a large-area electrocorticography device that can change shape via integrated fluidic actuators.

Crop rotational diversity can mitigate climate-induced grain yield losses.

Diversified crop rotations have been suggested to reduce grain yield losses from the adverse climatic conditions increasingly common under climate change. Nevertheless, the potential for climate change adaptation of different crop rotational diversity (CRD) remains undetermined. We quantified how climatic conditions affect small grain and maize yields under different CRDs in 32 long-term (10-63 years) field experiments across Europe and North America.

Can environmental nebulization of lavender essential oil (L. angustifolia) improve welfare and modulate nasal microbiota of growing pigs?

The use of phytoextracts has been proposed as a method to improve animal welfare, also in pigs, by reducing stress and anxiety and improving performances. Lavandula angustifolia (Miller) essential oil (LaEO) is an interesting calming phytoextract that could be administered by inhalation for prolonged periods of time to help pigs coping with on-farm conditions. The aim of this study was to assess the effects of daily inhalation of vaporized LaEO on pigs' welfare and health indicators, and nasal microbiota, trying to understand whether this phytoextract represents a feasible tool to improve animal welfare under intensive farming conditions.

Isolation and characterization of mammary epithelial cells derived from Göttingen Minipigs: A comparative study versus hybrid pig cells from the IMI-ConcePTION Project.

The value of pig as "large animal model" is a well-known tool for translational medicine, but it can also be beneficial in studying animal health in a one-health vision. The ConcePTION Project aims to provide new information about the risks associated with medication use during breastfeeding, as this information is not available for most commonly used drugs. In the IMI-Conception context, Göttingen Minipigs have been preferred to hybrid pigs for their genetic stability and microbiological control.

Influence of age and seasonality on boar seminal plasma steroids quantification: A preliminary study.

Background And Aim: Seasonal changes, especially temperature and photoperiod, are well-known determining factors of swine reproductive capacity, but the underlying mechanisms remain unknown. This study aimed to investigate the effect of age and seasonal variations on boar seminal plasma steroids (dehydroepiandrosterone [DHEA], cortisol [CORT], and testosterone [TEST]) over 1 year.

Materials And Methods: Four commercial hybrid adult boars (Large White × Duroc), aged between 12 and 44 months, were repeatedly evaluated at the Department of Veterinary Medical Sciences of the University of Bologna.

Comparative evaluation of the effects of different activating media and temperatures on European eel (Anguilla anguilla) sperm motility assessed by computer assisted sperm analysis.

The European eel is a critically endangered teleost fish with very poor success rate for captive breeding and artificial reproduction. Therefore, to support its conservation, new strategies are needed to ensure fertilization. Objective analysis of sperm motility may be critical as it potentially represents one of the most important reproductive quality parameters.

Isolation of Vascular Wall Mesenchymal Stem Cells from the Thoracic Aorta of Adult Göttingen Minipigs: A New Protocol for the Simultaneous Endothelial Cell Collection.

Two main classes of perivascular multipotent populations have been described: the microvascular pericytes and the vascular wall mesenchymal stem cells (VW-MSCs). VW-MSCs are isolated from large vessels in many species and they participate in vascular remodeling together with other cellular components such as endothelial cells. Considering that the Göttingen Minipigs are widely used in Europe as a translational model in the field of cardiovascular diseases, the aim of the present research was to isolate VW-MSCs from the adult aorta of Göttingen Minipigs while preserving and also collecting endothelial cells.

Artificial Diuresis: Animal Studies on Efficacy and Safety of a New Miniaturized Device for Extracorporeal Ultrafiltration.

Introduction: We have recently developed a new miniaturized device for extracorporeal ultrafiltration (UF) to be used in patients with fluid overload: Artificial Diuresis-1 (AD1) (Medica S.p.A.

Maternal amoxicillin affects piglets colon microbiota: microbial ecology and metabolomics in a gut model.

The first weeks of life represent a crucial stage for microbial colonization of the piglets' gastrointestinal tract. Newborns' microbiota is unstable and easily subject to changes under stimuli or insults. Nonetheless, the administration of antibiotics to the sow is still considered as common practice in intensive farming for pathological conditions in the postpartum.

The p-ERG spatial acuity in the biomedical pig under physiological conditions.

Pigs are becoming an important pre-clinical animal species for translational ophthalmology, due to similarities with humans in anatomical and physiological patterns. Different models of eye disorders have been proposed, and they are good candidates to assess biocompatibility/functionality of retinal prostheses. Electroretinography is a common tool allowing to gain information on retinal function, with several types of electroretinogram (ERG) been implemented including full field (ff-ERG), multifocal (mf-ERG) and pattern (p-ERG).

Lithotripsy of Calcified Aortic Valve Leaflets by a Novel Ultrasound Transcatheter-Based Device.

The increasing incidence of calcific aortic valve disease necessitates the elaboration of new strategies to retard the progression of the pathology with an innovative solution. While the increasing diffusion of the transcatheter aortic valve replacements (TAVRs) allows a mini-invasive approach to aortic valve substitution as an alternative to conventional surgical replacement (SAVR) in an always larger patient population, TAVR implantation still has contraindications for young patients. In addition, it is liable to undergo calcification with the consequent necessity of re-intervention with conventional valve surgery or repeated implantation in the so-called TAVR-in-TAVR procedure.

Development of a Pig Mammary Epithelial Cell Culture Model as a Non-Clinical Tool for Studying Epithelial Barrier-A Contribution from the IMI-ConcePTION Project.

The ConcePTION project aims at generating further knowledge about the risks related to the use of medication during breastfeeding, as this information is lacking for most commonly used drugs. Taking into consideration multiple aspects, the pig model has been considered by the consortium as the most appropriate choice. The present research was planned to develop an efficient method for the isolation and culture of porcine Mammary Epithelial Cells (pMECs) to study the mammary epithelial barrier in vitro.

Animal Models for In Vivo Lactation Studies: Anatomy, Physiology and Milk Compositions in the Most Used Non-Clinical Species: A Contribution from the ConcePTION Project.

The present review aims to summarize the main features of mammary gland anatomy, and the physiology of lactation and colostrum/milk in the most commonly used animal species for regulatory toxicity. The final goal is the selection of a preferred animal species to be enrolled in studies investigating the potential transfer of drugs and exogenous molecules through milk, within the Innovative Medicines Initiative (IMI) funded project ConcePTION. Reference data regarding humans were also collected and analyzed in order to highlight critical similarities and differences with the studied species.

A comprehensive review on non-clinical methods to study transfer of medication into breast milk - A contribution from the ConcePTION project.

Breastfeeding plays a major role in the health and wellbeing of mother and infant. However, information on the safety of maternal medication during breastfeeding is lacking for most medications. This leads to discontinuation of either breastfeeding or maternal therapy, although many medications are likely to be safe.

A novel porcine model of acid-induced esophageal damage for preliminary functional evaluations of anti-gastroesophageal reflux disease medical devices.

Aim: The aim of the study was to set up a porcine model of acid-induced damage and to evaluate its performance by means of multichannel intraluminal impedance and pH (MII-pH) live recording, histology, and Evans blue (EB) permeability assay.

Materials And Methods: Thirteen esophagi, collected at a slaughterhouse, were ablated of their sphincters, pinned upright on a support, and placed in a thermostatic hood at 37°C with two infusion tubes and an MII-pH probe inserted in the top end. Three esophagi (histology controls) were only left in the hood for 3.

Quantification of Hair Corticosterone, DHEA and Testosterone as a Potential Tool for Welfare Assessment in Male Laboratory Mice.

Steroids, providing information regarding several biological patterns including stress and sexual behavior, have been investigated in different matrices in laboratory mice. Data regarding hair quantification, indicative of longer timespans when compared to blood and saliva, are lacking. The aim of the work was to analyze the hormonal hair profile of laboratory male mice and to investigate potential relationships with age and housing, as a potential tool for welfare assessment.

Barrier Effect of a New Topical Agent on Damaged Esophageal Mucosa: Experimental Study on an ex vivo Swine Model.

Purpose: AL2106 is a new medical device based on a mixture of chondroitin sulphate in a xyloglucan and glycerol solution made to maximize its bioadhesive capability to the esophageal mucosa. The aim of the present study was twofold to evaluate the AL2106 protective effect on the esophageal mucosa when exposed to an acidic solution mimicking gastric reflux and to assess the resilience of this effect to saline washing.

Materials And Methods: A porcine ex vivo model was used and the effects of the new medical device were compared to a sodium alginate suspension (SAS) already present on the market which was assumed as reference.