A porcine model of acute necrotizing pancreatitis.

Background/objectives: Acute necrotizing pancreatitis is a common disease in humans and leads to significant and world-wide morbidity and mortality. Exploration of new pharmaceutical agents for the treatment of this disease frequently rests on rodent models that may not be relevant for spontaneous human disease and also preclude collecting multiple blood samples. Goal of this project was to establish an experimental model for acute necrotizing pancreatitis in pigs that mirrors the development of systemic complications of acute pancreatitis in humans as a prelude to clinical trials in humans.

Controlling mitochondrial membrane architecture via MIC60 determines viral replication to promote anti-viral immunity.

Virus-infected cells often exhibit dramatic cellular changes accompanied by altered mitochondrial function. The contribution of factors shaping the inner mitochondrial membrane (IMM) and cristae architecture to viral replication is insufficiently understood. Single-cell transcriptomics applying vesicular stomatitis virus infection suggests involvement of factors determining IMM architecture following infection.

Myoglobin expression improves T-cell metabolism and antitumor effector function.

Background: The tumor microenvironment is frequently hypoxic and characterized by a scarcity of nutritional resources including a shortage of glucose. As effector T cells have high energy demands, tumor metabolism can contribute to T-cell dysfunction and exhaustion.

Methods: In this study, we determined hypoxia in spleen and tumor tissue from tumor-bearing C57BL/6J mice using reverse transcription polymerase chain reaction (RT-PCR), histology and flow cytometry.

Evaluation of different intramuscular injectable anesthetic combinations in rabbits: Impact on anesthetic depth, physiological parameters, and EEG recordings.

Rabbits have a high anesthesia-related mortality rate because of their small size, high metabolic rate and challenging airway management. This study aimed to investigate different combinations of intramuscularly administered anesthetics in New Zealand White rabbits, focusing on their effects on anesthetic depth, physiological parameters, and electroencephalogram (EEG) recordings. Defined doses ketamine (K), esketamine (SK), medetomidine (M), dexmedetomidine (D), midazolam (Mi), and butorphanol (B) were investigated and compared in five different combinations: KM (25/0.

Hypoxia Preconditioned Serum Hydrogel (HPS-H) Accelerates Dermal Regeneration in a Porcine Wound Model.

Harnessing the body's intrinsic resources for wound healing is becoming a rapidly advancing field in regenerative medicine research. This study investigates the effects of the topical application of a novel porcine Hypoxia Preconditioned Serum Hydrogel (HPS-H) on wound healing using a minipig model over a 21-day period. Porcine HPS exhibited up to 2.

Conjugation of Polycationic Peptides Extends the Efficacy Spectrum of β-Lactam Antibiotics.

Antibiotic-resistant enterococci represent a significant global health challenge. Unfortunately, most β-lactam antibiotics are not applicable for enterococcal infections due to intrinsic resistance. To extend their antimicrobial spectrum, polycationic peptides are conjugated to examples from each of the four classes of β-lactam antibiotics.

Influence of Heart Rate and Change in Wavefront Direction through Pacing on Conduction Velocity and Voltage Amplitude in a Porcine Model: A High-Density Mapping Study.

Background: Understanding the dynamics of conduction velocity (CV) and voltage amplitude (VA) is crucial in cardiac electrophysiology, particularly for substrate-based catheter ablations targeting slow conduction zones and low voltage areas. This study utilizes ultra-high-density mapping to investigate the impact of heart rate and pacing location on changes in the wavefront direction, CV, and VA of healthy pig hearts.

Methods: We conducted in vivo electrophysiological studies on four healthy juvenile pigs, involving various pacing locations and heart rates.

The purinergic receptor P2X7 as a modulator of viral vector-mediated antigen cross-presentation.

Introduction: Modified Vaccinia Virus Ankara (MVA) is a safe vaccine vector inducing long- lasting and potent immune responses. MVA-mediated CD8T cell responses are optimally induced, if both, direct- and cross-presentation of viral or recombinant antigens by dendritic cells are contributing.

Methods: To improve the adaptive immune responses, we investigated the role of the purinergic receptor P2X7 (P2RX7) in MVA-infected feeder cells as a modulator of cross-presentation by non-infected dendritic cells.

Oral Delivery of the Vancomycin Derivative FU002 by a Surface-Modified Liposomal Nanocarrier.

Oral delivery of peptide therapeutics faces multiple challenges due to their instability in the gastrointestinal tract and low permeation capability. In this study, the aim is to develop a liposomal nanocarrier formulation to enable the oral delivery of the vancomycin-peptide derivative FU002. FU002 is a promising, resistance-breaking, antibiotic which exhibits poor oral bioavailability, limiting its potential therapeutic use.

Improved pharmacokinetics and enhanced efficacy of the vancomycin derivative FU002 using a liposomal nanocarrier.

Antibiotic resistance still represents a global health concern which diminishes the pool of effective antibiotics. With the vancomycin derivative FU002, we recently reported a highly potent substance active against Gram-positive bacteria with the potential to overcome vancomycin resistance. However, the translation of its excellent antimicrobial activity into clinical efficiency could be hampered by its rapid elimination from the blood stream.

Bispecific soluble cytokine receptor-nanobody fusions inhibit Interleukin (IL-)6 trans-signaling and IL-12/23 or tumor necrosis factor (TNF) signaling.

At least 0.5% of people in the Western world develop inflammatory bowel disease (IBD). While antibodies that block tumor necrosis factor (TNF) α and Interleukin (IL-)23 have been approved for the treatment of IBD, IL-6 antibodies failed in the phase II clinical trial due to non-tolerable side effects.

Nociception in Chicken Embryos, Part III: Analysis of Movements before and after Application of a Noxious Stimulus.

Many potentially noxious interventions are performed on chicken embryos in research and in the poultry industry. It is therefore essential and in the interest of animal welfare to be able to precisely define the point at which a chicken embryo is capable of nociception in ovo. The present part III of a comprehensive study examined the movements of developing chicken embryos with the aim of identifying behavioral responses to a noxious stimulus.

Nociception in Chicken Embryos, Part II: Embryonal Development of Electroencephalic Neuronal Activity as a Prerequisite for Nociception.

Chicken culling has been forbidden in Germany since 2022; male/female selection and male elimination must be brought to an embryonic status prior to the onset of nociception. The present study evaluated the ontogenetic point at which noxious stimuli could potentially be perceived/processed in the brain . EEG recordings from randomized hyperpallial brain sites were recorded and noxious stimuli were applied.

Simultaneous quantification of Gadoxetic acid and Cisplatin in hepatocellular carcinomas using laser ablation-inductively coupled plasma-mass spectrometry.

The gadolinium-based contrast agent Gadoxetic acid and the platinum-based antitumor agent Cisplatin were quantitatively imaged in liver and liver cancer (hepatocellular carcinoma, HCC) tissue of rats by means of laser ablation-inductively coupled plasma-mass spectrometry. HCC bearing rats simultaneously received a tail vein injection of the hepatocyte-specific magnetic resonance imaging contrast agent Gadoxetic acid and a transarterial injection of Cisplatin 15 min before sacrifice and liver removal. Resecting HCC with adjacent liver tissue allows the comparison of Gd, Pt, and endogenous elements like Fe, Cu, and Zn in the various tissue types.

Electroanatomical Conduction Characteristics of Pig Myocardial Tissue Derived from High-Density Mapping.

Background: Ultra-high-density mapping systems allow more precise measurement of the heart chambers at corresponding conduction velocities (CVs) and voltage amplitudes (VAs). Our aim for this study was to define and compare a basic value set for unipolar CV and VA in all four heart chambers and their separate walls in healthy, juvenile porcine hearts using ultra-high-density mapping.

Methods: We used the Rhythmia Mapping System to create electroanatomical maps of four pig hearts in sinus rhythm.

Nociception in Chicken Embryos, Part I: Analysis of Cardiovascular Responses to a Mechanical Noxious Stimulus.

Although it is assumed that chicken embryos acquire the capacity for nociception while developing in the egg, an exact time point has not yet been specified. The present research was an exploratory study aiming to determine when the capacity of nociception emerges during embryonic development in chickens. Changes in blood pressure and heart rate (HR) in response to a noxious mechanical stimulus at the base of the beak versus a light touch on the beak were examined in chicken embryos between embryonic days (EDs) 7 and 18.

ADAMTS-7 Modulates Atherosclerotic Plaque Formation by Degradation of TIMP-1.

Background: The locus was genome-wide significantly associated with coronary artery disease. Lack of the ECM (extracellular matrix) protease ADAMTS-7 (A disintegrin and metalloproteinase-7) was shown to reduce atherosclerotic plaque formation. Here, we sought to identify molecular mechanisms and downstream targets of ADAMTS-7 mediating the risk of atherosclerosis.

Application of a topical anesthetic reduces pain-associated parameters during spermatic cord transection in piglet castration using a minimal anesthesia model.

Objective: This study assessed the use of a topical anesthetic as a feasible approach to reduce pain during piglet castration using a minimal anesthesia protocol.

Animals: 18 male piglets, aged 3-6 days, were included in this study.

Methods: A minimal anesthetic state was induced with isoflurane administered by facemask, with anesthetic depth individually adjusted based on responses to interdigital pinch.

Constitutive Activation of gp130 in T Cells Results in Senescence and Premature Aging.

IL-6 family members contribute to host defense through the stimulation of acute-phase signaling, hematopoiesis, immune reactions, and regenerative processes. To investigate essential mechanisms that are linked toward a constitutively activated gp130 signaling, we generated and characterized a mouse model that reflects a constitutive and cytokine-independent activation of JAK/STAT3 signaling by Lgp130 in CD4- and CD8-positive T cells. Lgp130 is an engineered form of gp130 in which dimerization and activation are forced by a leucine zipper.

Behavior of Piglets in an Observation Arena before and after Surgical Castration with Local Anesthesia.

Surgical castration of piglets is generally recognized as a painful procedure, but there is currently no gold standard for the assessment of pain behavior in piglets. However, pain assessment is essential for evaluating the effectiveness of local anesthetics. In this study, we investigated the efficacy of four local anesthetics in terms of pain relief during and after surgical castration in three sequential study parts.

Differential temporal development of alveoli and the alveolar capillary network in the postnatal rat lung.

Quantitative data about the internal lung structure are needed to better understand normal and pathological lung development. Aberrant lung development causes deficits in alveolar and microvascular development; however, the normal temporal relationship between these processes is still not fully understood. We hypothesized that alveolar and capillary development show a differential time pattern.

Nociception-Induced Changes in Electroencephalographic Activity and FOS Protein Expression in Piglets Undergoing Castration under Isoflurane Anaesthesia.

The objective of this study was to investigate the electroencephalographic reaction pattern and FOS protein expression in male piglets undergoing surgical castration under light isoflurane anaesthesia with or without local anaesthesia. The experiment was conducted under isoflurane anaesthesia to exclude the effect of the affective components of pain on the measurements. Changes in the oscillatory activity of the cerebral cortex over a 90 s period after noxious stimulation or simulated interventions were analysed.

Nanoparticles are linked to polar lipids in xylem sap of temperate angiosperm species.

In previous research, xylem sap of angiosperms has been found to include low concentrations of nanoparticles and polar lipids. A major goal of this study was to test predictions arising from the hypothesis that the nanoparticles consist largely of polar lipids from the original cell content of vessel elements. These predictions included that polar lipid and nanoparticle concentrations would be correlated, that they both do not pass through pit membranes and that they do not vary seasonally because they originate from living vessel element cells.

Evaluation of Two Injection Techniques in Combination with the Local Anesthetics Lidocaine and Mepivacaine for Piglets Undergoing Surgical Castration.

The present study evaluated the effects of two injection techniques in combination with lidocaine or mepivacaine for piglets undergoing castration. To improve ease of use, a cannula with side holes (one-step fenestrated (F)) was invented to simultaneously deliver a local anesthetic into the testis and scrotum and was compared to a two-step injection technique. The distribution of a lidocaine/contrast agent mixture using the two methods was examined using computed tomography.

Impact of Linker Modification and PEGylation of Vancomycin Conjugates on Structure-Activity Relationships and Pharmacokinetics.

As multidrug-resistant bacteria represent a concerning burden, experts insist on the need for a dramatic rethinking on antibiotic use and development in order to avoid a post-antibiotic era. New and rapidly developable strategies for antimicrobial substances, in particular substances highly potent against multidrug-resistant bacteria, are urgently required. Some of the treatment options currently available for multidrug-resistant bacteria are considerably limited by side effects and unfavorable pharmacokinetics.