Human-Scale Liver Harvest and Decellularization for Preclinical Research

Background: Positron-emission-tomography (PET) using 18F labeled florbetaben allows noninvasive in vivo-assessment of amyloid-beta (Aβ), a pathological hallmark of Alzheimer’s disease (AD). In preclinical research, [18F]-florbetaben-PET has already been used to test the amyloid-lowering potential of new drugs, both in humans and in transgenic models of cerebral amyloidosis. The aim of this study was to characterize the spatial pattern of cerebral uptake of [18F]-florbetaben in the APPswe/ PS1dE9 mouse model of AD in comparison to histologically determined number and size of cerebral Aβ plaques. Methods: Both, APPswe/PS1dE9 and wild type mice at an age of 12 months were investigated by smallanimal PET/CT after intravenous injection of [18F]-florbetaben. High-resolution magnetic resonance imaging data were used for quantification of the PET data by volume of interest analysis. The standardized uptake values (SUVs) of [18F]-florbetaben in vivo as well as post mortem cerebral Aβ plaque load in cortex, hippocampus and cerebellum were analyzed. Results: Visual inspection and SUVs revealed an increased cerebral uptake of [18F]-florbetaben in APPswe/ PS1dE9 mice compared with wild type mice especially in the cortex, the hippocampus and the cerebellum. However, SUV ratios (SUVRs) relative to cerebellum revealed only significant differences in the hippocampus between the APPswe/PS1dE9 and wild type mice but not in cortex; this differential effect may reflect the lower plaque area in the cortex than in the hippocampus as found in the histological analysis. Conclusion: The findings suggest that histopathological characteristics of Aβ plaque size and spatial distribution can be depicted in vivo using [18F]-florbetaben in the APPswe/PS1dE9 mouse model.

Download Full-text

SGLT-2 Inhibition: Novel Therapeutics for Reno-and Cardioprotection in Diabetes Mellitus

Current Diabetes Reviews ◽

10.2174/1573399814666180417121246 ◽

2019 ◽

Vol 15 (5) ◽

pp. 349-356 ◽

Cited By ~ 2

Author(s):

Angus Gill ◽

Stephen P. Gray ◽

Karin A. Jandeleit-Dahm ◽

Anna M.D. Watson

Keyword(s):

Sympathetic Nerve Activity ◽

Diabetic Patients ◽

Protective Effects ◽

Preclinical Research ◽

Type 2 Diabetic Patients ◽

Nerve Activity ◽

Current State ◽

Glucose Reabsorption ◽

Type 2 Diabetic

Background: The sodium glucose co-transporter 2 (SGLT2) is primarily located within S1 of the renal proximal tubule being responsible for approximately 90% of glucose re-uptake in the kidney. Inhibition of SGLT2 is an exciting new pharmacological approach for the reduction of blood glucose in type 2 diabetic patients via inhibition of tubular glucose reabsorption. In addition to lowering glucose, this group of drugs has shown significant cardiovascular and renal protective effects. Conclusion: This review aims to outline the current state of preclinical research and clinical trials for different SGLT2 inhibitors and outline some of the proposed mechanisms of action, including possible effects on sympathetic nerve activity, which may contribute to the unexpected beneficial cardiovascular and reno-protective effects of this class of compounds.

Download Full-text

Cannabidiol Modulates the Motivational and Anxiety-Like Effects of 3,4-Methylenedioxypyrovalerone (MDPV) in Mice

International Journal of Molecular Sciences ◽

10.3390/ijms22158304 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8304

Author(s):

Laia Alegre-Zurano ◽

Raúl López-Arnau ◽

Miguel Á. Luján ◽

Jordi Camarasa ◽

Olga Valverde

Keyword(s):

Conditioned Place Preference ◽

Learning Task ◽

Place Preference ◽

Bath Salts ◽

Self Administration ◽

Preclinical Research ◽

Plus Maze ◽

Life Threatening ◽

Synthetic Cathinone ◽

High Responders

3,4-Methylenedioxypyrovalerone (MDPV) is a new psychoactive substance (NPS) and the most widespread and life-threatening synthetic cathinone of the “bath salts”. Preclinical research has proven the cocaine-like psychostimulant effects of MDPV and its potential for abuse. Cannabidiol (CBD) is a non-psychotropic phytocannabinoid that has emerged as a new potential treatment for drug addiction. Here, we tested the effects of CBD (20 mg/kg) on MDPV (2 mg/kg)-induced conditioned place preference and MDPV (0.05 and 0.075 mg/kg/infusion) self-administration paradigms. In addition, we assessed the effects of the co-administration of CBD and MDPV (3 and 4 mg/kg) on anxiety-like behaviour using the elevated plus maze (EPM). CBD mitigated the MDPV-induced conditioned place preference. On the contrary, CBD administration throughout the MDPV (0.075 mg/kg/infusion) self-administration increased drug-seeking and taking behaviours, but only in the high-responders group of mice. Furthermore, CBD exerted anxiolytic-like effects, exclusively in MDPV-treated mice. Taken together, our results indicate that CBD modulation of MDPV-induced motivational responses in mice varies depending on the requirements of the learning task, resulting in a complex response. Therefore, further research attempting to decipher the behavioural and molecular interactions between CBD and MDPV is needed.

Download Full-text

Are We Paving the Way to Dig Out of the “Pandemic Hole”? A Narrative Review on SARS-CoV-2 Vaccination: From Animal Models to Human Immunization

Medical Sciences ◽

10.3390/medsci9030053 ◽

2021 ◽

Vol 9 (3) ◽

pp. 53

Author(s):

Giuseppe Tardiolo ◽

Pina Brianti ◽

Daniela Sapienza ◽

Pia dell’Utri ◽

Viviane Di Dio ◽

...

Keyword(s):

Animal Models ◽

Viral Vector ◽

Herd Immunity ◽

Population Level ◽

Narrative Review ◽

Therapeutic Interventions ◽

Preclinical Research ◽

Inactivated Vaccines ◽

Preclinical And Clinical Studies ◽

Social Upheaval

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new pathogen agent causing the coronavirus infectious disease (COVID-19). This novel virus originated the most challenging pandemic in this century, causing economic and social upheaval internationally. The extreme infectiousness and high mortality rates incentivized the development of vaccines to control this pandemic to prevent further morbidity and mortality. This international scenario led academic scientists, industries, and governments to work and collaborate strongly to make a portfolio of vaccines available at an unprecedented pace. Indeed, the robust collaboration between public systems and private companies led to resolutive actions for accelerating therapeutic interventions and vaccines mechanism. These strategies contributed to rapidly identifying safe and effective vaccines as quickly and efficiently as possible. Preclinical research employed animal models to develop vaccines that induce protective and long-lived immune responses. A spectrum of vaccines is worldwide under investigation in various preclinical and clinical studies to develop both individual protection and safe development of population-level herd immunity. Companies employed and developed different technological approaches for vaccines production, including inactivated vaccines, live-attenuated, non-replicating viral vector vaccines, as well as acid nucleic-based vaccines. In this view, the present narrative review provides an overview of current vaccination strategies, taking into account both preclinical studies and clinical trials in humans. Furthermore, to better understand immunization, animal models on SARS-CoV-2 pathogenesis are also briefly discussed.

Download Full-text

Cannabidiol as a Potential Treatment for Anxiety and Mood Disorders: Molecular Targets and Epigenetic Insights from Preclinical Research

International Journal of Molecular Sciences ◽

10.3390/ijms22041863 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1863

Author(s):

Philippe A. Melas ◽

Maria Scherma ◽

Walter Fratta ◽

Carlo Cifani ◽

Paola Fadda

Keyword(s):

Mood Disorders ◽

Cannabinoid Receptors ◽

Transient Receptor Potential ◽

Therapeutic Potential ◽

Molecular Targets ◽

Receptor Potential ◽

Transient Receptor Potential Vanilloid ◽

Preclinical Research ◽

Neuropsychiatric Diseases ◽

Transient Receptor

Cannabidiol (CBD) is the most abundant non-psychoactive component of cannabis; it displays a very low affinity for cannabinoid receptors, facilitates endocannabinoid signaling by inhibiting the hydrolysis of anandamide, and stimulates both transient receptor potential vanilloid 1 and 2 and serotonin type 1A receptors. Since CBD interacts with a wide variety of molecular targets in the brain, its therapeutic potential has been investigated in a number of neuropsychiatric diseases, including anxiety and mood disorders. Specifically, CBD has received growing attention due to its anxiolytic and antidepressant properties. As a consequence, and given its safety profile, CBD is considered a promising new agent in the treatment of anxiety and mood disorders. However, the exact molecular mechanism of action of CBD still remains unknown. In the present preclinical review, we provide a summary of animal-based studies that support the use of CBD as an anxiolytic- and antidepressant-like compound. Next, we describe neuropharmacological evidence that links the molecular pharmacology of CBD to its behavioral effects. Finally, by taking into consideration the effects of CBD on DNA methylation, histone modifications, and microRNAs, we elaborate on the putative role of epigenetic mechanisms in mediating CBD’s therapeutic outcomes.

Download Full-text

The functional vascular anatomy of the swine for research

Vascular ◽

10.1177/1708538121996500 ◽

2021 ◽

pp. 170853812199650

Author(s):

Joseph Edwards ◽

Hossam Abdou ◽

Neerav Patel ◽

Marta J Madurska ◽

Kelly Poe ◽

...

Keyword(s):

Translational Research ◽

Functional Anatomy ◽

Three Dimensional ◽

Vascular Anatomy ◽

Review Article ◽

Imaging Data ◽

Preclinical Research ◽

Iodinated Contrast ◽

Translational Research Program ◽

And Function

Objectives Swine ( Sus Scrofa) are utilized broadly in research settings, given similarities to human vessel size and function; however, there are some important differences for clinicians to understand in order to interpret and perform translational research. This review article uses angiograms acquired in the course of a translational research program to present a description of the functional anatomy of the swine. Methods Digital subtraction angiography and computed tomography angiography were obtained throughout the course of multiple studies utilizing power injection with iodinated contrast. Subtracted two-dimensional images and three-dimensional multiplanar reformations were utilized post image acquisition to create maximal intensity projections and three-dimensional renderings of using open-source software (OsiriX). These imaging data are presented along with vessel measurements for reference. Results An atlas highlighting swine vascular anatomy, with an emphasis on inter-species differences that may influence how studies are conducted and interpreted, was compiled. Conclusions Swine are utilized in broad-reaching fields for preclinical research. While many similarities between human and swine vasculature exist, there are important differences to consider when conducting and interpreting research. This review article highlights these differences and presents accompanying images to inform clinicians gaining experience in swine research.

Download Full-text