Development and application of a novel in vivo overload model of the Achilles tendon in rat.

Repetitive overload is a primary factor in tendon injury, causing progressive accumulation of matrix damage concurrent with a cellular response. However, it remains unclear how these events occur at the initial stages of the disease, making it difficult to identify appropriate treatment approaches. Here, we describe the development of a new model to cyclically load the Achilles tendon (AT) of rats in vivo and investigate the initial structural and cellular responses. The model utilizes controlled dorsiflexion of the ankle joint applied near maximal dorsiflexion, for 10,000 cycles at 3 Hz. Animals were subjected to a single bout of in vivo loading under anaesthesia, and either culled immediately (without recovery from anaesthesia), or 48 h or 4-weeks post-loading. Macro strains were assessed in cadavers, whilst tendon specific microdamage was assessed through collagen-hybridizing peptide (CHP) immunohistochemistry which highlighted a significant rise in CHP staining in loaded ATs compared to contralateral controls, indicating an accumulation of overload-induced damage. Staining for pro-inflammatory mediators (IL-6 and COX-2) and matrix degradation markers (MMP-3 and -13) also suggests an initial cellular response to overload. Model validation confirmed our approach was able to explore early overload-induced damage within the AT, with microdamage present and no evidence of broader musculoskeletal damage. The new model may be implemented to map the progression of tendinopathy in the AT, and thus study potential therapeutic interventions.

Parentally deprived juvenile Owl monkeys suffer from long-term high infection rates but not from altered hair cortisol concentrations nor from stereotypic behaviours.

BACKGROUND: In captive colonies, owl monkeys' mothers sometimes reject their newborns. To prevent, mortality infants are manually raised by veterinarians. Both parental separation and rejection are stressful experiences, associated with elevated stress, physical, and behavioural disorders. The effect of parental deprivation in IVITA's owl monkeys stress profiles and health is unknown. METHODS: We compared stress biomarkers such as hair cortisol (using cortisol ELISA), stereotypic behaviours (with infrared cameras), and infection histories in juveniles separated from parents soon after birth (n = 14, ~17 months) and controls (n = 11, ~17 months). RESULTS: Parentally deprived owl monkeys show higher infection rates than controls (p = .001). However, they display no higher incidence of biomarkers of stress: Neither stereotypic behaviour nor cortisol in hair was different between cohorts. Irrespective of deprivation status, rates of infection, and concentration of cortisol in hair were positively associated (R2 = .29, p = .005). CONCLUSION: Early parental deprivation and natural high levels of cortisol secretion are associated with elevated infection levels in the IVITA owl monkey juveniles detectable up to 17 months post separation.

Teaching a culture of care: why it matters / Enseñar una cultura del cuidado: por qué es importante

The use of animal in biomedical research remains a critical compromise. Research and higher education institutions play a major role in educating on the use of animal and such training is expected to translate into the development of a culture of care practice across all staff working with animals. But nurturing a "culture of care" and impacting in professional attitudes in the field of animal research remains challenging due to its social, ethical and different institutional frameworks. From an educational perspective, current practice remains challenged by the need for better integration of inter-cultural perceptions on animal welfare, supported by more cross disciplinary integration in educational curriculum including the relevance of the 3Rs principles and promoting reflective practice strategies. Institutional support is crucial to provide a safe, and supportive framework to promote such caring ethos. Our aim is to discuss practical actions to implement and assess culture of care, highlighting its direct impact on the professional integrity of staff which is directly linked to research and education excellence. Seeking a global welfare for all the beings involved and supporting individual and team reflective practice will provide better tools to guarantee the best care of the animals (AU)

El uso de animales en la investigación biomédica sigue siendo un compromiso crítico. Las instituciones de investigación y educación superior desempeñan un papel importante en la enseñanza sobre el uso de animales y se espera que dicha capacitación se traduzca en el desarrollo de una cultura de prácticas de cuidado en todo el personal que trabaja con animales. Pero fomentar una "cultura del cuidado" e impactar en las actitudes profesionales en el campo de la investigación animal sigue siendo un desafío debido a las diferentes perspectivas sociales, éticas y regulatorias. Desde una perspectiva educativa, la práctica actual sigue siendo cuestionada por la necesidad de una mejor integración de las percepciones interculturales sobre el bienestar animal, respaldada por una mayor integración interdisciplinaria en el plan de estudios, incluida la relevancia de los principios de las 3R y la promoción de estrategias de práctica reflexiva. El apoyo institucional es crucial para proporcionar un marco seguro y de apoyo para promover este espíritu solidario. Nuestro objetivo es discutir acciones prácticas para implementar y evaluar la cultura de la atención, destacando su impacto directo en la integridad profesional del personal que está directamente relacionado con la excelencia en investigación y educación. Buscar un bienestar global para todos los seres involucrados y apoyar la práctica reflexiva individual y de equipo proporcionará mejores herramientas para garantizar el mejor cuidado de los animales (AU)

L'ús d'animals en la recerca biomèdica continua sent un compromís crític. Les institucions de recerca i educació superior exerceixen un paper important en l'ensenyament sobre l'ús d'animals i s'espera que aquesta capacitació es tradueixi en el desenvolupament d'una cultura de pràctiques de cura en tot el personal que treballa amb animals. Però fomentar una "cultura de la cura" i impactar en les actituds professionals en el camp de la recerca animal continua sent un desafiament degut a les diferents perspectives socials, ètiques i reguladores. Des d'una perspectiva educativa, la pràctica actual continua sent qüestionada per la necessitat d'una millor integració de les percepcions interculturals sobre el benestar animal, recolzada per una major integració interdisciplinària en el pla d'estudis, inclosa la rellevància dels principis de les 3R i la promoció d'estratègies de pràctica reflexiva. El suport institucional és crucial per a proporcionar un marc segur i de suport per a promoure aquest esperit solidari. El nostre objectiu és discutir accions pràctiques per a implementar i avaluar la cultura de l'atenció, destacant el seu impacte directe en la integritat professional del personal que està directament relacionat amb l'excel·lència en recerca i educació. Buscar un benestar global per a tots els éssers involucrats i donar suport a la pràctica reflexiva individual i d'equip proporcionarà millors eines per a garantir la millor cura dels animals (AU)

Identification of an essential endogenous regulator of blood-brain barrier integrity, and its pathological and therapeutic implications.

The blood-brain barrier (BBB), a critical guardian of communication between the periphery and the brain, is frequently compromised in neurological diseases such as multiple sclerosis (MS), resulting in the inappropriate passage of molecules and leukocytes into the brain. Here we show that the glucocorticoid anti-inflammatory messenger annexin A1 (ANXA1) is expressed in brain microvascular endothelial cells, where it regulates BBB integrity. In particular, ANXA1(-/-) mice exhibit significantly increased BBB permeability as a result of disrupted interendothelial cell tight junctions, essentially related to changes in the actin cytoskeleton, which stabilizes tight and adherens junctions. This situation is reminiscent of early MS pathology, a relationship confirmed by our detection of a selective loss of ANXA1 in the plasma and cerebrovascular endothelium of patients with MS. Importantly, this loss is swiftly restored by i.v. administration of human recombinant ANXA1. Analysis in vitro confirms that treatment of cerebrovascular endothelial cells with recombinant ANXA1 restores cell polarity, cytoskeleton integrity, and paracellular permeability through inhibition of the small G protein RhoA. We thus propose ANXA1 as a critical physiological regulator of BBB integrity and suggest it may have utility in the treatment of MS, correcting BBB function and hence ameliorating disease.

Age-dependent effects of chronic fluoxetine treatment on the serotonergic system one week following treatment.

RATIONALE: Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are increasingly used for the treatment of depression in children. Limited data are, however, available on their effects on brain development and their efficacy remains debated. Moreover, previous experimental studies are seriously hampered in their clinical relevance. OBJECTIVES: The aim of the present study was to investigate putative age-related effects of a chronic treatment with fluoxetine (5 mg/kg, either orally or i.p. for 3 weeks, 1 week washout) using conventional methods (behavioral testing and binding assay using [(123)I]ß-CIT) and a novel magnetic resonance imaging (MRI) approach. METHODS: Behavior was assessed, as well as serotonin transporter (SERT) availability and function through ex vivo binding assays and in vivo pharmacological MRI (phMRI) with an acute fluoxetine challenge (10 mg/kg oral or 5 mg/kg i.v.) in adolescent and adult rats. RESULTS: Fluoxetine caused an increase in anxiety-like behavior in treated adult, but not adolescent, rats. On the binding assays, we observed increased SERT densities in most cortical brain regions and hypothalamus in adolescent, but not adult, treated rats. Finally, reductions in brain activation were observed with phMRI following treatment, in both adult and adolescent treated animals. CONCLUSION: Collectively, our data indicate that the short-term effects of fluoxetine on the 5-HT system may be age-dependent. These findings could reflect structural and functional rearrangements in the developing brain that do not occur in the matured rat brain. phMRI possibly will be well suited to study this important issue in the pediatric population.