Toward evidence-based severity assessment in rat models with repeated seizures: I. Electrical kindling.

Objective: Rodent epilepsy models can significantly contribute to our understanding of pathophysiological mechanisms and to validation of biomarker and target candidates. Evidence-based severity assessment is a presupposition for the ethical evaluation of animal experimentation allowances as well as for the development of efficacious refinement concepts.

Methods: Aiming to improve our understanding of the impact of experimental procedures and repeated seizures, we have completed a comprehensive behavioral and biochemical analysis assessing various parameters that can inform about the influence of an electrical kindling paradigm on well-being in rats.

Practicable methods for histological section thickness measurement in quantitative stereological analyses.

The accuracy of quantitative stereological analysis tools such as the (physical) disector method substantially depends on the precise determination of the thickness of the analyzed histological sections. One conventional method for measurement of histological section thickness is to re-embed the section of interest vertically to its original section plane. The section thickness is then measured in a subsequently prepared histological section of this orthogonally re-embedded sample.

Identification and genetic characterization of polyomaviruses in estrildid and fringillid finches.

Polyomavirus infections were detected in 40 companion bird individuals belonging to a broad species range of estrildid and fringillid finches and originating from 21 different bird aviaries. Based on partial virus protein 1 (VP1) sequences, the viruses were identified as Serinus canaria polyomavirus 1 and Pyrrhula pyrrhula polyomavirus 1. Serinus canaria polyomavirus 1 was found in 18 birds belonging to one estrildid and four fringillid species.

The Munich MIDY Pig Biobank - A unique resource for studying organ crosstalk in diabetes.

Objective: The prevalence of diabetes mellitus and associated complications is steadily increasing. As a resource for studying systemic consequences of chronic insulin insufficiency and hyperglycemia, we established a comprehensive biobank of long-term diabetic transgenic pigs, a model of mutant gene-induced diabetes of youth (MIDY), and of wild-type (WT) littermates.

Methods: Female MIDY pigs (n = 4) were maintained with suboptimal insulin treatment for 2 years, together with female WT littermates (n = 5).

Preliminary evaluation of cytosine-phosphate-guanine oligodeoxynucleotides bound to gelatine nanoparticles as immunotherapy for canine atopic dermatitis.

Cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN) are a promising new immunotherapeutic treatment option for canine atopic dermatitis (AD). The aim of this uncontrolled pilot study was to evaluate clinical and immunological effects of gelatine nanoparticle (GNP)-bound CpG ODN (CpG GNP) on atopic dogs. Eighteen dogs with AD were treated for 8 weeks (group 1, n=8) or 18 weeks (group 2, n=10).

Plasma protein, haematologic and blood chemistry changes in African grey parrots (Psittacus erithacus) experimentally infected with bornavirus.

Bornaviruses are considered to be the causative agent of proventricular dilatation disease (PDD) in psittacine birds. In order to detect haematological and blood chemistry changes during the development of PDD and a possible correlation with clinical signs and the virological status, six African grey parrots (Psittacus erithacus) were experimentally infected with parrot bornavirus 4 (PaBV-4) by subcutaneous route. All six parrots developed clinical signs of varying extent and successful infection was confirmed in all the birds by seroconversion or detection of RNA of the PaBV-4 infection strain.

Mitochondrial Dysregulation Secondary to Endoplasmic Reticulum Stress in Autosomal Dominant Tubulointerstitial Kidney Disease - UMOD (ADTKD-UMOD).

'Autosomal dominant tubulointerstitial kidney disease - UMOD' (ADTKD-UMOD) is caused by impaired maturation and secretion of mutant uromodulin (UMOD) in thick ascending limb of Henle loop (TAL) cells, resulting in endoplasmic reticulum (ER) stress and unfolded protein response (UPR). To gain insight into pathophysiology, we analysed proteome profiles of TAL-enriched outer renal medulla samples from ADTKD-UMOD and control mice by quantitative LC-MS/MS. In total, 212 differentially abundant proteins were identified.

Corrective Osteotomy of a Metacarpal Deviation Caused by Fracture in a 9-Month-Old German Fleckvieh Heifer.

Objective: To describe the surgical treatment of a metacarpal deviation caused by an untreated Salter-Harris type I fracture in a heifer.

Study Design: Case report.

Animal: 9-month-old German Fleckvieh heifer.

Recovery of erectile function comparing autologous nerve grafts, unseeded conduits, Schwann-cell-seeded guidance tubes and GDNF-overexpressing Schwann cell grafts.

Dissection of the cavernous nerves during radical prostatectomy for prostate cancer eliminates spontaneous erections. Using the rat as an experimental model, we compared the regenerative capacity of autologous nerve grafts and Schwann-cell-seeded nerve guides. After bilateral excision of cavernous nerve segments, cavernous nerves were reconstructed using unseeded silicon tubes, nerve autografts and silicon tubes seeded with either Glial-cell-line-derived (GDNF)-overexpressing or green fluorescent protein (GFP)-expressing Schwann cells (SCs) (16 study nerves per group).

Histopathologic examination of the genital tract in rabbits treated once or twice with a slow-release deslorelin implant for reversible suppression of ovarian function.

A total of 13 rabbits were treated with a subcutaneous deslorelin long-term release implant (4.7 mg) to study the effect on ovarian function and histologic features of the uterus. Seven rabbits (group 1) were implanted with a slow-release deslorelin implant before onset of puberty for 273 days as a part of a previous study.

Molecular characterization of a recently identified circovirus in zebra finches (Taeniopygia guttata) associated with immunosuppression and opportunistic infections.

A recently identified circovirus (family Circoviridae) was detected in 14 zebra finches (Taeniopygia guttata) from seven aviaries and hobbyist breeders using polymerase chain reaction followed by sequencing. Full genome sequences of virus strains from six zebra finches consistently revealed characteristic circoviral genomic features such as a stem-loop structure and two major open reading frames (ORFs) encoding the replication-associated protein and the putative capsid protein. One further ORF encoding a protein of unknown function was additionally identified in all six genomes.

A novel HSP90 inhibitor with reduced hepatotoxicity synergizes with radiotherapy to induce apoptosis, abrogate clonogenic survival, and improve tumor control in models of colorectal cancer.

The chaperone heat shock protein 90 (HSP90) crucially supports the maturation, folding, and stability of a variety of client proteins which are of pivotal importance for the survival and proliferation of cancer cells. Consequently, targeting of HSP90 has emerged as an attractive strategy of anti-cancer therapy, and it appears to be particularly effective in the context of molecular sensitization towards radiotherapy as has been proven in preclinical models of different cancer entities. However, so far the clinical translation has largely been hampered by suboptimal pharmacological properties and serious hepatotoxicity of first- and second-generation HSP90 inhibitors.

Comparative aspects of rodent and nonrodent animal models for mechanistic and translational diabetes research.

The prevalence of diabetes mellitus, which currently affects 387 million people worldwide, is permanently rising in both adults and adolescents. Despite numerous treatment options, diabetes mellitus is a progressive disease with severe comorbidities, such as nephropathy, neuropathy, and retinopathy, as well as cardiovascular disease. Therefore, animal models predictive of the efficacy and safety of novel compounds in humans are of great value to address the unmet need for improved therapeutics.

Ubiquitous LEA29Y Expression Blocks T Cell Co-Stimulation but Permits Sexual Reproduction in Genetically Modified Pigs.

We have successfully established and characterized a genetically modified pig line with ubiquitous expression of LEA29Y, a human CTLA4-Ig derivate. LEA29Y binds human B7.1/CD80 and B7.

Sperm membrane integrity in fresh and frozen-thawed canine semen samples: a comparison of vital stains with the NucleoCounter SP-100.

The objective of this study was to assess sperm membrane integrity in canine semen samples using three different vital stains and the NucleoCounter SP-100 (NC). In addition, the occurrence of half-stained sperm heads, the influence of investigator, and storage-related artifacts using stained smears were examined. Forty fresh (30 dogs) and 40 frozen-thawed (28 dogs) canine semen samples were analyzed.

Sebaceous lipids are essential for water repulsion, protection against UVB-induced apoptosis and ocular integrity in mice.

Sebocytes, which are characterized by lipid accumulation that leads to cell disruption, can be found in hair follicle-associated sebaceous glands (SGs) or in free SGs such as the Meibomian glands in the eyelids. Because genetic tools that allow targeting of sebocytes while maintaining intact epidermal lipids are lacking, the relevance of sebaceous lipids in health and disease remains poorly understood. Using Scd3, which is expressed exclusively in mature sebocytes, we established a mouse line with sebocyte-specific expression of Cre recombinase.

Melting curve analysis in canine lymphoma by calculating maximum fluorescence decrease.

PARR is widely used in the diagnostics of canine lymphoma. In human and veterinary medicine, melting curve analysis (MCA) has successfully been introduced to facilitate the process. Since visual interpretation of melting curves can be rather subjective, the purpose of this study was to develop an objective interpretation of melting curves by calculating the maximum fluorescence decrease (dF ) within a defined rise of temperature.

Tissue Sampling Guides for Porcine Biomedical Models.

This article provides guidelines for organ and tissue sampling adapted to porcine animal models in translational medical research. Detailed protocols for the determination of sampling locations and numbers as well as recommendations on the orientation, size, and trimming direction of samples from ∼50 different porcine organs and tissues are provided in the Supplementary Material. The proposed sampling protocols include the generation of samples suitable for subsequent qualitative and quantitative analyses, including cryohistology, paraffin, and plastic histology; immunohistochemistry;in situhybridization; electron microscopy; and quantitative stereology as well as molecular analyses of DNA, RNA, proteins, metabolites, and electrolytes.

Age-related Qualitative Histological and Quantitative Stereological Changes in the Equine Pituitary.

The aim of this study was to characterize the age-related morphological changes in the equine pituitary and to identify features that allow distinction between pituitary pars intermedia dysfunction (PPID)-associated and non-functional/age-associated pars intermedia (PI) adenoma. Pituitary glands of all horses submitted for necropsy examination at the Institute of Veterinary Pathology, Ludwig Maximilians University Munich, between 2008 and 2012 were examined. The pituitary glands of 124 horses were weighed, cut into ∼2 mm slices and examined histologically.

Tailored Pig Models for Preclinical Efficacy and Safety Testing of Targeted Therapies.

Despite enormous advances in translational biomedical research, there remains a growing demand for improved animal models of human disease. This is particularly true for diseases where rodent models do not reflect the human disease phenotype. Compared to rodents, pig anatomy and physiology are more similar to humans in cardiovascular, immune, respiratory, skeletal muscle, and metabolic systems.

Reversible estrous cycle suppression in prepubertal female rabbits treated with slow-release deslorelin implants.

The aim of this study was to examine the long-term effect of a 4.7-mg deslorelin GnRH analog implant on ovarian function in the prepubertal female rabbit. Seven female rabbits (group 1) were treated with the implant at the age of 60 days.

Comparative Oncology: Evaluation of 2-Deoxy-2-[18F]fluoro-D-glucose (FDG) Positron Emission Tomography/Computed Tomography (PET/CT) for the Staging of Dogs with Malignant Tumors.

Introduction: 2-Deoxy-2-[18F]fluoro-D-glucose PET/CT is a well-established imaging method for staging, restaging and therapy-control in human medicine. In veterinary medicine, this imaging method could prove to be an attractive and innovative alternative to conventional imaging in order to improve staging and restaging. The aim of this study was both to evaluate the effectiveness of this image-guided method in canine patients with spontaneously occurring cancer as well as to illustrate the dog as a well-suited animal model for comparative oncology.

Complete genome sequence of a novel circovirus from zebra finch.

A novel circovirus was identified in zebra finches (Taeniopygia guttata). The genome of the circovirus strain, designated 8454V25-1, comprised 1,982 nucleotides with two major open reading frames encoding a replication-associated protein and a viral capsid protein.