Archives des Publications - ETAP-LAB

Publication: “Aging alters the vulnerability pattern to amyloid-beta oligomers in wild-type mice: a behavioral and neurobiological study”

agavtheve — Sat, 02 May 2026 07:00:26 +0000

Publication on Aging alters the vulnerability pattern to amyloid-beta oligomers in wild-type mice: a behavioral and neurobiological study. Allouche, A., Colin, J., Birck, C. et al. Published in Alzheimer’s Research & Therapy (2026).

Read the full open-access article here: https://rdcu.be/fj1zB (DOI: https://link.springer.com/article/10.1186/s13195-026-02051-2)

Authors: Ahmad Allouche 1†, Julie Colin1*†, Catherine Birck 2, Henri Schroeder 3, Valentin Tallandier 1, Marion Baldoni 1, Christophe Muller 1, Mohamed Afrassi 1 & Nicolas Violle 1.

*Ahmad Allouche and Julie Colin contributed equally to this work.

Affiliated:

1 ETAP-Lab, 54500 Vandoeuvre-lès-Nancy, France
2 Plateforme de Biologie Structurale Intégrée, CBI-IGBMC, CNRS UMR 7104, Inserm U1258, University of Strasbourg, 67400 Illkirch, France
3 UMR Inserm 1256 nGERE – Lorraine University, 9 Avenue de La Forêt de Haye, 54500 Vandoeuvre-Lès-Nancy, France

Abstract:

Background
Aging is the primary risk factor for sporadic Alzheimer’s disease (AD). While amyloid-beta oligomers (AβOs) accumulation is a key neuropathological process in AD, their specific effects in aged brains and how aging modulates brain response to AβOs remains poorly understood. We investigated how aging contributes to AβO-induced neurotoxicity and cognitive deficits in mice.

Methods
After biochemical and in vitro characterizations on primary cultures of cortical neurons, AβOs or their vehicle were intracerebrally injected into both 3- and 18-month-old wild-type mice. A broad spectrum of assays including synaptic markers, neuroinflammation, apoptosis and cognitive functions was used to establish a preliminary characterization of the interplay between age and AβOs. In vivo data were analyzed using a multifactorial design (Treatment × Age), with two-way ANOVA or other appropriate statistical models.

Results
Old mice had significantly reduced synaptic proteins SNAP-25 and PSD-95, elevated neuroinflammatory markers, and increased neuronal apoptosis in hippocampus and cortex, despite showing cognitive performances similar to young mice. All brain biomarkers were worsened after AβO injection in both young and old mice. Age and AβO effects either accumulated or interacted to promote neuroinflammation and apoptosis, depending on brain areas, whereas their effects on synaptic proteins were strictly additive. Moreover, AβO injection induced only mild spatial memory deficits in young mice, in contrast with those observed in old mice in both episodic and spatial memory tests.

Discussion
Whereas the young brain showed resilience to maintain memory performances after AβO injection, the coping capacities of the aging brain were exceeded by AβO effects. At the neurobiological level, age and AβO effects were mainly additive, but also acted synergistically in a brain region-dependent vulnerability pattern. This study highlights the value of incorporating aging into preclinical models to improve their translational validity and enhance their relevance for drug testing targeting early stages of sporadic AD.

Keywords: Aging, Alzheimer’s disease, Amyloid-beta oligomers, Neurodegeneration, Neuroinflammation, Memory.

L’article Publication: “Aging alters the vulnerability pattern to amyloid-beta oligomers in wild-type mice: a behavioral and neurobiological study” est apparu en premier sur ETAP-LAB.

Publication: “Animal-origin-free method for generating blood vessel organoids”

agavtheve — Thu, 05 Mar 2026 08:00:00 +0000

Publication on Animal-origin-free method for generating blood vessel organoids. Hoffmann, A., Schorn, D., Thönig, J. et al.. Published in Sci Rep 16, 12096 (2026).

Read the full article: https://doi.org/10.1038/s41598-026-42977-z

Authors: Alexander Hoffmann1,2, David Schorn1, Jakob Thönig1, Yu-Hsiang Teng1, Jean-François Bisson3 & Teodor E. Yordanov1

Affiliated:

1 Angios FlexCo, Exlgasse 24, 6020 Innsbruck, Austria.
2 Department of Internal Medicine II, Medical University Innsbruck, Innsbruck, Austria.
3 Department of Dermatology, ETAP-Lab, Vandoeuvre-lès-Nancy, France.

Abstract:

Blood vessel organoids (BVOs) represent a promising tool for modeling vascular diseases, drug screening, and regenerative therapies. However, current protocols for BVO generation are complex, labor-intensive, and reliant on animal-derived extracellular matrices (ECM) such as Matrigel, limiting reproducibility, scalability, and clinical applicability. We developed a simplified, animal-origin-free protocol for BVO generation that addresses current limitations and enables high-throughput automated workflows. The method employs ultra-low attachment 96-well U-bottom plates for standardized aggregation and differentiation of human induced pluripotent stem cells (hiPSCs) in a human derived collagen-based extracellular matrix. Unlike conventional protocols where aggregates are embedded in a two-layer ECM, our approach utilizes a single-layer, which we termed “sitting drop”. This innovative approach requires considerably fewer materials and handling steps and is compatible with high-throughput automated machines. BVO generation utilizing the here described optimized protocol resulted in the formation of BVOs with reproducible morphology and cellular composition. Flow cytometry confirmed the presence of CD31⁺ endothelial cells and PDGFRβ⁺ pericytes in BVOs, generated in sitting drops in ultra-low adhesive U-bottom shaped 96 well plates, with cell population percentages comparable to those observed in traditional two-layer BVO cultures. In vivo transplantation of mature BVOs in a mouse full-thickness skin wound model demonstrated integration of BVO derived cells into host vessels, highlighting their potential in cell-based therapies. Our study presents a robust and animal-origin-free method for BVO generation based on single-layer “sitting drop” cultures. This protocol maintains cellular integrity while enhancing reproducibility and automation-readiness, paving the way for high-throughput screening and clinical translation of vascular organoid technology.

Keywords: Blood vessel organoids (BVO), Extracellular matrix (ECM), Collagen, High-throughput, Organoids, Bioengineering

L’article Publication: “Animal-origin-free method for generating blood vessel organoids” est apparu en premier sur ETAP-LAB.

Publication on Functional discrimination of CSF from Alzheimer’s patients in a brain on chip platform

Gregory — Mon, 01 Sep 2025 09:00:05 +0000

Publication: Functional discrimination of CSF from Alzheimer’s patients in a brain on chip platform.

Sci Rep 15, 29738 (2025).

Authors: Miny, L., Rontard, J., Allouche, A. et al.

Affiliated:

NETRI (Lyon, France)
Hospices Civils de Lyon – Department of Biochemistry and Molecular Biology, Neurodegenerative Pathologies (Bron, France)
Lyon Neurosciences Research Center (CNRS UMR 5292 / INSERM U1028)
ETAP-Lab – Preclinical Efficacy CRO (Vandoeuvre-Lès-Nancy, France)

Abstract:

Neurodegenerative diseases, including Alzheimer’s disease (AD), present significant diagnostic challenges due to overlapping symptoms and the invasive, time-consuming, and costly nature of current diagnostic methods. While AD remains the only neurodegenerative disorder for which biomarkers in cerebrospinal fluid (CSF), such as amyloid beta peptide (Aβ), are available for clinical diagnosis, similar tools are lacking for other neurodegenerative conditions. This diagnostic gap hinders timely and accurate differential diagnoses, limiting patient access to appropriate clinical trials and therapeutic interventions. In this study, we developed a compartmentalized microfluidic platform to facilitate differential diagnosis of neurodegenerative diseases by providing an initial screening tool to guide patients toward targeted clinical pathways. Using CSF samples from AD patients with confirmed diagnoses, we showed a proof of concept to distinguish between non neurodegenerative (NN) and Alzheimer’s samples. Human glutamatergic neurons derived from induced pluripotent stem cells (iPSCs) were exposed to synthetic Aβ oligomers (AβO) and patient CSF to assess their effects on neuronal network activity. Neuronal responses were recorded via microelectrode array (MEA) before and after treatments, with tetrodotoxin (TTX) serving as a control for validating modulation of the neuronal network. Our findings demonstrated that key electrophysiological metrics extracted from MEA recordings can tend to differentiate AD from non-neurodegenerative CSF samples. This standardized platform not only provides a robust approach for AD biomarker validation but also offers a foundation for broader differential diagnosis of neurodegenerative diseases. By enabling more accurate patient stratification, this tool could have the potential to direct patients toward appropriate clinical trials, enabling the diagnosis of a broader range of neurodegenerative diseases. This approach has the potential to expand the patient population included in research and accelerate the development of new therapeutic strategies.

Keywords: Proteinopathy, Protein Aggregation,Neurodegenerative Diseases, Oligomers, Brain On Chip, diagnosis of neurodegenerative disorders, preclinical biomedical research.

L’article Publication on Functional discrimination of CSF from Alzheimer’s patients in a brain on chip platform est apparu en premier sur ETAP-LAB.

Publication on NDD’s cellular models – Scientific Reports (Nature)

Gregory — Thu, 17 Jul 2025 12:30:07 +0000

Consult the publication in which ETAP-LAB was mentioned and acknowledged for our in vitro hippocampal neuron model—challenged with own-manufactured Tau oligomers: “A novel allosteric GCase modulator prevents Tau accumulation in GBA1WT and GBA1L444P/L444P cellular models. Sci Rep 15, 17646 (2025).”

Published 21 May 2025 – Ciccaldo, M., Pérez-Carmona, N., Piovesana, E. et al. https://www.nature.com/articles/s41598-025-02346-8

Authors: Matteo Ciccaldo1, Natàlia Pérez-Carmona2, Ester Piovesana1, Sara Cano-Crespo2, Ana Ruano2, Aida Delgado2, Ilaria Fregno3, Beatriz Calvo-Flores Guzmán4, Manolo Bellotto4, Maurizio Molinari3,5, Joanne Taylor6, Stéphanie Papin1, Ana María García-Collazo2 & Paolo Paganetti1,7,

Abstract:

A slow decline in the autophagy-lysosomal pathway is a hallmark of the normal aging brain. Yet, an acceleration of this cellular function may propel neurodegenerative events. In fact, mutations in genes associated with the autophagy-lysosomal pathway can lead to Parkinson’s disease. Also, amyloidogenic protein deposition is observed in lysosomal storage disorders, which are caused by genetic mutations representing risk factors for Parkinson’s disease. For example, Gaucher’s disease GBA1 mutations leading to defects in lysosomal sphingolipid metabolism cause α-synuclein accumulation. We observed that increased lysosomal Tau accumulation is found in human dermal fibroblasts engineered for inducible Tau expression. Inhibition of the GBA1 product GCase augmented Tau-dependent lysosomal stress and Tau accumulation. Here, we show increased Tau seed-induced Tau accumulation in Gaucher’s fibroblasts carrying GBA1 mutations when compared to normal fibroblasts. Pharmacological enhancement of GCase reversed this effect, notably, also in normal fibroblasts. This suggests that boosting GCase activity may represent a therapeutic strategy to slow down aging-dependent lysosomal deficits and brain protein deposition.

Keywords: Alzheimer’s disease, Mechanisms of disease, Parkinson’s disease

L’article Publication on NDD’s cellular models – Scientific Reports (Nature) est apparu en premier sur ETAP-LAB.

Publication: “Urolithin A provides cardioprotection and mitochondrial quality enhancement preclinically and improves human cardiovascular health biomarkers”

agavtheve — Tue, 11 Mar 2025 09:53:43 +0000

Cardiovascular diseases (CVDs) are the leading cause of global mortality. That’s why we are proud to share a groundbreaking study titled “Urolithin A provides cardioprotection and mitochondrial quality enhancement preclinically and improves human cardiovascular health biomarkers“. Liu, Sophia et al. iScience, Volume 28, Issue 2, 111814

Read the full study here: https://doi.org/10.1016/j.isci.2025.111814

Authors:

Sophia Liu1,8 ∙ Julie Faitg2,8 ∙ Charlotte Tissot2,8 ∙ Dimitris Konstantopoulos3 ∙ Ross Laws4 ∙ Guillaume Bourdier5 ∙ Pénélope A. Andreux6 ∙ Tracey Davey4 ∙ Hector Gallart-Ayala7 ∙ Julijana Ivanisevic7 ∙ Anurag Singh2 ∙ Chris Rinsch2 ∙ David J. Marcinek1 Send email to dmarc@uw.edu ∙ Davide D’Amico

Affiliations :

1 Department of Radiology, University of Washington Medical Center, Box 358050, Seattle, WA 98109, USA
2 Amazentis, EPFL Innovation Park, Lausanne, Switzerland
3 Genevia Technologies Oy, 33100 Tampere, Finland
4 Electron Microscopy Research Services, Newcastle University, Newcastle, UK
5 Syncrosome, Campus Luminy – Luminy Entreprises, 13288 Marseille, France
6 Vandria, EPFL Innovation Park, Lausanne, Switzerland
7 Metabolomics Platform, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
8 These authors contributed equally
9 Lead contact

This study highlights the potential of Urolithin A (UA), a post-biotic and mitophagy activator, to improve heart health by addressing mitochondrial dysfunctions. Preclinical model results show reduced cardiac dysfunction, while human trials indicate significant reductions in plasma ceramides, making UA a promising nutritional intervention for aging populations !
And hope for patients with Cardiovascular diseases.

Highlights
–> Urolithin A enhances heart mitochondrial quality in aging and heart failure models
–> Cardiac function decline in these models is reduced by urolithin A
–> In humans, urolithin A lowers plasma ceramides associated with heart disease risk
–> Urolithin A is a promising nutritional approach to support heart health as we age

Summary
Cardiovascular diseases (CVDs) remain the primary cause of global mortality. Nutritional interventions hold promise to reduce CVD risks in an increasingly aging population. However, few nutritional interventions are proven to support heart health and act mostly on blood lipid homeostasis rather than at cardiac cell level. Here, we show that mitochondrial quality dysfunctions are common hallmarks in human cardiomyocytes upon heart aging and in chronic conditions. Preclinically, the post-biotic and mitophagy activator, urolithin A (UA), reduced both systolic and diastolic cardiac dysfunction in models of natural aging and heart failure. At a cellular level, this was associated with a recovery of mitochondrial ultrastructural defects and mitophagy. In humans, UA supplementation for 4 months in healthy older adults significantly reduced plasma ceramides clinically validated to predict CVD risks. These findings extend and translate UA’s benefits to heart health, making UA a promising nutritional intervention to support cardiovascular function as we age.

L’article Publication: “Urolithin A provides cardioprotection and mitochondrial quality enhancement preclinically and improves human cardiovascular health biomarkers” est apparu en premier sur ETAP-LAB.

A signifiant milestone for our publication on Nutrients journal

Gregory — Wed, 12 Feb 2025 08:38:19 +0000

We wanted to highlight on our recent article on our psychopharmacology research “The Anxiolytic-like Properties of a Tryptic Hydrolysate of Bovine αs1 Casein Containing α-Casozepine Rely on GABAA Receptor Benzodiazepine Binding Sites but Not the Vagus Nerve” that has reached over 3000 views in MDPI Nutrients journal!

The published data on the anxiolytic-like properties of bovine αs1-casein (CH) support that:

α-casozepine is responsive for the anxiolytic-like effects of the alpha-s1-casein tryptic hydrolysate (CH).
CH anxiolytic-like effects are not mediated by the vagus nerve.
CH anxiolytic-like effects are least partially mediated by benzodiazepine binding site of GABAA receptors.

We would like to thank our readers for their support and interest in our research!

The paper is still available in our publication space, or in MDPI website

L’article A signifiant milestone for our publication on Nutrients journal est apparu en premier sur ETAP-LAB.

Improving Stroke Outcomes in Hyperglycemic Mice by Modulating tPA/NMDAR Signaling to Reduce Inflammation and Hemorrhages

Gregory — Mon, 08 Jan 2024 08:32:13 +0000

The pharmacological intervention for ischemic stroke hinges on intravenous administration of the recombinant tissue-type plasminogen activator (rtPA, Alteplase/Actilyse®) either as a standalone treatment or in conjunction with thrombectomy. However, despite its clinical significance, broader employment of rtPA is constrained due to the risk of hemorrhagic transformations (HTs). Furthermore, the presence of diabetes or chronic hyperglycemia is associated with an elevated risk of HT subsequent to thrombolysis. This detrimental impact of tPA on the neurovascular unit in hyperglycemic patients has been ascribed to its capacity to induce endothelial N-methyl-D-aspartate receptor (NMDAR) signaling, contributing to compromised blood-brain barrier integrity and neuroinflammatory processes. In a mouse model of thromboembolic stroke with chronic hyperglycemia, we assessed the effectiveness of rtPA and NAC (N-Acetylcysteine) as thrombolytic agents. We also tested the effect of blocking tPA/NMDAR signaling using a monoclonal antibody, Glunomab. Magnetic Resonance Imaging, speckle contrast imaging, flow cytometry, and behavioral tasks were used to evaluate stroke outcomes. In hyperglycemic animals, treatment with rtPA resulted in lower recanalization rates and increased HTs. Conversely, NAC treatment reduced lesion sizes while mitigating HTs. After a single administration either in standalone or combined with rtPA-induced thrombolysis, Glunomab reduced brain lesion volumes, HTs, and neuroinflammation after stroke, translating into improved neurological outcomes. Additionally, we demonstrated the therapeutic efficacy of Glunomab in combination with NAC or as a standalone strategy in chronic hyperglycemic animals. Counteracting tPA-dependent endothelial NMDAR signaling limits ischemic damages induced by both endogenous and exogenous tPA, including HTs and inflammatory processes following ischemic stroke in hyperglycemic animals.

Keywords: Animal model; Stroke; hemorrhagic transformations; diabetes

L’article Improving Stroke Outcomes in Hyperglycemic Mice by Modulating tPA/NMDAR Signaling to Reduce Inflammation and Hemorrhages est apparu en premier sur ETAP-LAB.

Dynamics of cerebral blood volume during and after middle cerebral artery occlusion in rats – Comparison between ultrafast ultrasound and dynamic susceptibility contrast-enhanced MRI measurements

Gregory — Thu, 21 Dec 2023 07:45:43 +0000

Tomographic perfusion imaging techniques are integral to translational stroke research paradigms that advance our understanding of the disease. Functional ultrasound (fUS) is an emerging technique that informs on cerebral blood volume (CBV) through ultrasensitive Doppler and flow velocity (CBFv) through ultrafast localization microscopy. It is not known how experimental results compare with a classical CBV-probing technique such as dynamic susceptibility contrast-enhanced perfusion MRI (DSC-MRI). To that end, we assessed hemodynamics based on uUS (n = 6) or DSC-MRI (n = 7) before, during and up to three hours after 90-minute filament-induced middle cerebral artery occlusion (MCAO) in rats. Recanalization was followed by a brief hyperperfusion response, after which CBV and CBFv temporarily normalized but progressively declined after one hour in the lesion territory. DSC-MRI data corroborated the incomplete restoration of CBV after recanalization, which may have been caused by the free-breathing anesthetic regimen. During occlusion, MCAO-induced hypoperfusion was more discrepant between either technique, likely attributable to artefactual signal mechanisms related to slow flow, and processing algorithms employed for either technique. In vivo uUS- and DSC-MRI-derived measures of CBV enable serial whole-brain assessment of post-stroke hemodynamics, but readouts from both techniques need to be interpreted cautiously in situations of very low blood flow.

Keywords: Cerebral blood volume; ischemic stroke; magnetic resonance imaging; reperfusion; ultrafast ultrasound.

L’article Dynamics of cerebral blood volume during and after middle cerebral artery occlusion in rats – Comparison between ultrafast ultrasound and dynamic susceptibility contrast-enhanced MRI measurements est apparu en premier sur ETAP-LAB.

A New Moisturiser Improves DNCB-induced Atopic Dermatitis-like Symptoms and Restores Skin Barrier Function in BALB/c Mice

Gregory — Thu, 13 Jul 2023 08:40:34 +0000

Introduction

Atopic dermatitis (AD) is a chronic, inflammatory skin disorder with eczematous and pruritic lesions. Topical moisturisers and either topical corticosteroids or calcineurin inhibitors are usually recommended. Restoring the skin barrier function alleviates AD symptoms.

Objective

To evaluate the efficacy of a new moisturiser compared to commercially available products in an AD murine model.

Methods

Experimental AD was induced with topical applications of 2,4-DiNitroChloroBenzene (DNCB) on the shaved back skin of BALB/c mice from Day 1 to Day 38. Mice were randomized to either Vehicle/-, DNCB/-, or DNCB/Eczekalm (test product), DNCB/Atopiclair®, or DNCB/Lipikar (reference products) groups. Once daily application of either Eczekalm or Atopiclair® or Lipikar on the AD lesion was performed from Day 32 to Day 38. The AD severity index (ADSI) and animal behaviour were monitored throughout the study. The trans-epidermal water loss (TEWL) was measured on the sacrifice day (Day 39).

Results

At Day39, ADSI in the DNCB/Eczekalm, DNCB/Lipikar, and DNCB/Atopiclair® groups were significantly lower by -70%, -68%, and -57%, respectively, as compared to DNCB/- (p < 0.001). No sign of erythema was observed in the DNCB/Eczekalm group. Mean scores of skin oedema, excoriation, and dryness in the DNCB/Eczekalm, DNCB/Lipikar, and DNCB/Atopiclair® groups were significantly lower than in the DNCB/-. No significant difference was observed between DNCB/Eczekalm and DNCB/Lipikar

Link to Pubmed

L’article A New Moisturiser Improves DNCB-induced Atopic Dermatitis-like Symptoms and Restores Skin Barrier Function in BALB/c Mice est apparu en premier sur ETAP-LAB.

The Anxiolytic-like Properties of a Tryptic Hydrolysate of Bovine αs1 Casein Containing α-Casozepine Rely on GABAA Receptor Benzodiazepine Binding Sites but Not the Vagus Nerve

Gregory — Sun, 22 May 2022 15:28:28 +0000

Background

A tryptic hydrolysate of bovine αs1-casein (CH) exerts anxiolytic-like properties in many species, including humans. This is mainly related to the presence of α-casozepine (α-CZP), which yields these properties in rodents. This study evaluates, in a rat model, the roles of the vagus nerve and the benzodiazepine binding site of GABAA receptors in the mode of action of CH.

Methods

The conditioned defensive burying test was used to evaluate anxiety.

Results

Participation of the vagus nerve in the mode of action of CH was excluded, as the global anxiety score in vagotomised rats was not significantly different from that of non-vagotomised animals. The blocking of the binding sites of benzodiazepines with flumazenil antagonised CH anxiolytic-like properties.

Conclusions

The vagus nerve does not play a role in the anxiolytic-like properties of CH. On the other hand, this anxiolytic-like activity relies on the benzodiazepine binding site of the GABAA receptors. This result is consistent with previous in vitro studies and, more specifically with the discovery of α-CZP, the peptide responsible for the anxiolytic-like properties of CH.

Keywords

GABAA; anxiolysis; casein tryptic hydrolysate; vagotomy; α-casozepine.

Link to Pubmed

L’article The Anxiolytic-like Properties of a Tryptic Hydrolysate of Bovine αs1 Casein Containing α-Casozepine Rely on GABAA Receptor Benzodiazepine Binding Sites but Not the Vagus Nerve est apparu en premier sur ETAP-LAB.

Antitumor Effect and Induced Immune Response Following Exposure of Hexaminolevulinate and Blue Light in Combination with Checkpoint Inhibitor in an Orthotopic Model of Rat Bladder Cancer

Gregory — Fri, 25 Feb 2022 14:59:18 +0000

Previous studies have found that use of hexaminolevulinate (HAL) and blue light cystoscopy (BLC) during treatment of bladder cancer had a positive impact on overall survival after later cystectomy, indicating a potential treatment effect beyond improved diagnostic accuracy. The aim of our study was to determine whether HAL and BL mimicking clinically relevant doses in an orthotopic rat model could have therapeutic effect by inducing modulation of a tumor-specific immune response. We also assessed whether administration with a checkpoint inhibitor could potentiate any effects observed. Rats were subjected to HAL BL alone and in combination with anti-PD-L1 and assessed for anti-tumor effects and effects on immune markers. Positive anti-tumor effect was observed in 63% and 31% of rats after, respectively, 12 and 30 days after the procedure, together with a localization effect of CD3+ and CD8+ cells after 30 days. Anti-tumor effect at 30 days increases from 31% up to 38% when combined with intravesical anti-PD-L1. In conclusion, our study demonstrated treatment effects with indications of systemic immune activation at diagnostic doses of HAL and blue light. The observed treatment effect seemed to be enhanced when used in combination with intravesically administrated immune checkpoint inhibitor.

Keywords: Hexvix®; PDT; bladder cancer; immune checkpoints; photodiagnosis.

Link to Pubmed

L’article Antitumor Effect and Induced Immune Response Following Exposure of Hexaminolevulinate and Blue Light in Combination with Checkpoint Inhibitor in an Orthotopic Model of Rat Bladder Cancer est apparu en premier sur ETAP-LAB.

Post-acute delivery of α5-GABAA antagonist, S 44819, improves functional recovery in juvenile rats following stroke

Gregory — Mon, 15 Nov 2021 10:15:44 +0000

Hypo-excitability was reported in the peri-infarct tissue following stroke, an effect counteracted by a blockage of α5-GABAA receptors in adult rodents. Our present study aims to evaluate the effect of a selective α5-GABAA receptor antagonist, S 44819, in stroke in juvenile animals. We have set up and characterized an original model of transient ischemic stroke in 28 day-old Sprague-Dawley rats (45-min occlusion of the middle cerebral artery by intraluminal suture). In this model, S 44819 (1, 3 and 10 mg/kg, b.i.d) was orally administered from day 3 to day 16 after stroke onset. Sensorimotor recovery was assessed on day 1, day 9 and day 16 after stroke onset. Results show that rats treated with S 44819 at the doses of 3 and 10 mg/kg displayed a significant improvement of the neurological deficits (neuroscore) on day 9 and day 16, when compared with animals treated with vehicle. Grip-test data analysis reveals that rats treated with S 44819 at the dose of 3 mg/kg displayed a better recovery on day 9 and day 16. These results are in agreement with those previously observed in adult rats, demonstrating that targeting α5-GABAA receptors improves neurological recovery after stroke in juvenile rats.

Keywords: Animal model; Behavioural tests; GABA; Recovery; Stroke.

Link to Pubmed

L’article Post-acute delivery of α5-GABAA antagonist, S 44819, improves functional recovery in juvenile rats following stroke est apparu en premier sur ETAP-LAB.

Early Ultrafast Ultrasound Imaging of Cerebral Perfusion correlates with Ischemic Stroke outcomes and responses to treatment in Mice

Gregory — Thu, 03 Sep 2020 08:18:12 +0000

In the field of ischemic cerebral injury, precise characterization of neurovascular hemodynamic is required to select candidates for reperfusion treatments. It is thus admitted that advanced imaging-based approaches would be able to better diagnose and prognose those patients and would contribute to better clinical care. Current imaging modalities like MRI allow a precise diagnostic of cerebral injury but suffer from limited availability and transportability. The recently developed ultrafast ultrasound could be a powerful tool to perform emergency imaging and long term follow-up of cerebral perfusion, which could, in combination with MRI, improve imaging solutions for neuroradiologists.

Methods: In this study, in a model of in situ thromboembolic stroke in mice, we compared a control group of non-treated mice (N=10) with a group receiving the gold standard pharmacological stroke therapy (N=9). We combined the established tool of magnetic resonance imaging (7T MRI) with two innovative ultrafast ultrasound methods, ultrafast Doppler and Ultrasound Localization Microscopy, to image the cerebral blood volumes at early and late times after stroke onset and compare with the formation of ischemic lesions.

Results: Our study shows that ultrafast ultrasound can be used through the mouse skull to monitor cerebral perfusion during ischemic stroke. In our data, the monitoring of the reperfusion following thrombolytic within the first 2 h post stroke onset matches ischemic lesions measured 24 h. Moreover, similar results can be made with Ultrasound Localization Microscopy which could make it applicable to human patients in the future.

Conclusion: We thus provide the proof of concept that in a mouse model of thromboembolic stroke with an intact skull, early ultrafast ultrasound can be indicative of responses to treatment and cerebral tissue fates following stroke. It brings new tools to study ischemic stroke in preclinical models and is the first step prior translation to the clinical settings.

Keywords: Ischemic stroke, Thrombolysis, Ultrasound Imaging, Ultrasound Localization Microscopy, Outcome

L’article Early Ultrafast Ultrasound Imaging of Cerebral Perfusion correlates with Ischemic Stroke outcomes and responses to treatment in Mice est apparu en premier sur ETAP-LAB.

Publication: “Isoproterenol-induced heart failure in rat heart: evaluation and cardioprotective strategy.”

agavtheve — Thu, 21 Mar 2019 09:14:00 +0000

Research publication titled: “Isoproterenol-induced heart failure in rat heart: evaluation and cardioprotective strategy.” G. Bourdier, et al. SYNCROSOME. Presented during Printemps de la Cardiologie 2019. Cardiovascular Diseases Supplements Volume 11, Issue 2, April 2019, Page 230

Read the full study here/DOI: https://doi.org/10.1016/j.acvdsp.2019.02.107

Authors:

G. Bourdier, S Robelet,

Affiliations : SYNCROSOME, Luminy biotech entreprises, Marseille, France

Abstract
Introduction
It is well established that cardiac remodelling plays a pivotal role in the development of heart failure (HF), a leading cause of death worldwide. Meanwhile, a preclinical rat model of isoproterenol (Iso)-induced HF causes sympathetic hyperactivity, an important factor of cardiac remodelling, hemodynamic changes and cardiac fibrosis development. Several studies showed that metoprolol, a β1-adrenergic receptor (β1-AR) blocker prevents cardiac dysfunction following prolonged β-AR stimulation in different preclinical models.
Objective
We evaluated the cardioprotective effects of metoprolol on cardiac remodelling and diastolic function in a severe Iso-induced HF model using echocardiography and cardiac pressure measurement.
Method
Rats received Iso injections (Iso; 5 mg/kg/day, N = 5), metoprolol (Meto; 24 mg/kg/day) + Iso 5 (Iso + Meto, N = 6), or vehicle (N = 9) for 7 days. Left ventricular (LV) dimensions and function were followed-up by echocardiography before and after the treatment to assess LV hypertrophy. After echocardiography, LV end-diastolic pressure (LVEDP) was recorded to assess ventricular compliance and rat hearts were used for cardiac remodelling analysis.
Results
One week of Iso injections significantly increased LVEDP (+ 48%) and was associated with a major LV hypertrophy, characterised by a significant increase in LV mass (+ 33%) and a thickening of the LV walls observed by echocardiography. Simultaneous treatment with metoprolol prevented diastolic dysfunction and LV remodelling. Hypertrophy and fibrosis will be analysed in each group by histology (on-going experiments).

Conclusion
Metoprolol afforded a cardioprotective effect on cardiac remodelling and diastolic dysfunction in Iso-induced HF model. Echocardiography and LVEDP measurements validate the reversibility of hypertrophic HF, and Iso-induced HF developed in rat could represent an effective and predictive preclinical model for evaluating antihypertrophic and antifibrotic agents.

L’article Publication: “Isoproterenol-induced heart failure in rat heart: evaluation and cardioprotective strategy.” est apparu en premier sur ETAP-LAB.

Evaluation of the antidepressant- and anxiolytic-like effects of a hydrophilic extract from the green seaweed Ulva sp. in rats

Gregory — Wed, 20 Jun 2018 14:41:03 +0000

OBJECTIVES: The green seaweed Ulva sp. contains a large amount of ulvans, a family of sulphated polysaccharides. The present study was designed to investigate in rats the antidepressant- and anxiolytic-like effects of a hydrophilic extract of Ulva sp. (MSP) containing about 45% of ulvans.

METHODS: After a 14-day administration of MSP at doses of 10, 20 and 40 mg/kg/day, 48 and 60 male adult Wistar rats were respectively tested in the elevated plus-maze (EPM) and the forced swimming test (FST). In the FST, MSP effects were compared to the reference antidepressant drug imipramine (IMI) (10 mg/kg/day). Acute and sub-chronic toxicities of the extract were also assessed in male and female rats following OECD guidelines.

RESULTS: MSP treatment did not modify anxiety-related behaviour in the EPM. In contrast, MSP induced a dose-dependent reduction of immobility behaviour in the FST. At the highest tested dose of 40 mg/kg, MSP displayed a significant antidepressant-like effect similar to IMI. MSP did not modify the exploratory behaviour of rats in the open field test and did not produce any toxic effect.

DISCUSSION: MSP may potentially represent a good adjunct or alternative to existing antidepressant therapeutics. Further studies are necessary to confirm the mechanism of action of MSP and its modulation of brain functioning.

L’article Evaluation of the antidepressant- and anxiolytic-like effects of a hydrophilic extract from the green seaweed Ulva sp. in rats est apparu en premier sur ETAP-LAB.

Lactobacillus salivarius LA307 and Lactobacillus rhamnosus LA305 attenuate skin inflammation in mice

Gregory — Tue, 12 Jun 2018 14:34:42 +0000

Oral probiotics potential for the management of dermatological diseases is vast. However, results of available studies in skin diseases, such as atopic dermatitis (AD), are inconsistent, partly because probiotic effects are strain specific. Careful selection of probiotic strains is therefore indispensable to ensure efficacy of treatment. In this study, Lactobacillus salivarius LA307, Lactobacillus rhamnosus LA305 and Bifidobacterium bifidumPI22, three strains that were previously identified for their interesting immunomodulatory properties in allergy and/or colitis models, were assessed in the prevention of chronic skin inflammation induced by repeated applications of 12-O-tetradecanoylphorbol-13-acetate in hairless SKH-1 mice. Macroscopic and microscopic evaluation of skin lesions was performed together with measurements of serum levels of interleukin (IL)-1β, IL-6, tumour necrosis factor alpha (TNF-α), IL-17, IL-22, IL-10 and IL-4. Daily oral treatment with the three strains at the dose of 1×109 cfu/day for 3 weeks limited the development of chronic skin inflammation, the effects being strain dependent. Indeed the two Lactobacillus strains significantly limited the intensity of skin inflammation both at the macroscopic and microscopic levels. Macroscopic observations were correlated to the histological observations and the resulting microscopic score. This limitation of the development of AD-like skin lesions involved the modulation of cytokine production. Treatment with the two Lactobacillus strains induced a decrease in the serum levels of pro-inflammatory cytokines IL-1β, IL-6, TNF-α, IL-17, IL-22 and at the opposite an increase in the production of the anti-inflammatory cytokine IL-10 and also of IL-4. Globally, B. bifidum PI22 had lower benefits. These results obtained in mice suggest that L. salivarius LA307 and L. rhamnosus LA305 could be good candidates for preserving skin integrity and homeostasis via the modulation of the gut microbiota and that their use could be beneficial in dermatological conditions such as AD.

L’article Lactobacillus salivarius LA307 and Lactobacillus rhamnosus LA305 attenuate skin inflammation in mice est apparu en premier sur ETAP-LAB.

Antidiarrheal and Antinociceptive Effects of a Probiotic Mixture in Rats

Gregory — Wed, 21 Dec 2016 12:37:59 +0000

Probiotics have been shown to have preventive and therapeutic effects on diarrhea. Because effects tend to be strain specific, benefit of a strain or mixture has to be substantiated by experimental evidence. The aim of this study was to investigate the antidiarrheal and antinociceptive effects of a probiotic mixture (Lactibiane Imedia®, PiLeJe). Castor oil-induced diarrhea test was performed in Wistar rats following oral administration of probiotics (20 × 109, 30 × 109 or 40 × 109 CFU/kg), loperamide (5 mg/kg) or vehicle (water; 10 mL/kg). Time to initial evacuation, number of feces and diarrheal feces, fresh weight and water content of the feces and body weight loss were monitored. Behavioral parameters (eye closing, abnormal posture, activity, fur aspect) were used as pain indices. Probable mechanisms of action were evaluated by using the castor oil-induced enteropooling and charcoal meal transit tests. Probiotics significantly and dose-dependently delayed onset time to first feces and had a beneficial effect on all other parameters (p<0.05 versus vehicle). This effect was lower than loperamide on most of parameters evaluated. Loperamide totally stopped diarrhea (100%) but also blocked defecation (by 98.5%) whereas probiotics strongly inhibited diarrhea (>90%) at the two highest doses tested (30 × 109 or 40 × 109 CFU/kg) without completely blocking defecation (65.7% at 30 × 109 CFU/kg). Behavioral parameters were improved with probiotics compared to vehicle, improvement that was not observed with loperamide. Probiotics significantly and dose-dependently decreased the volume of intestinal fluid (p<0.05 versus vehicle) in the enteropooling test and transit time of charcoal meal. These results indicate that the probiotic mixture tested is strongly antidiarrheic through the combination of antimotility and antisecretory properties. Observations are also in favor of an antinociceptive effect. Agents that can decrease both intestinal hypersecretion and motility are very useful in the management of diarrhea therefore, our probiotic mixture could be an effective alternative to standard drugs.

Link to the article

L’article Antidiarrheal and Antinociceptive Effects of a Probiotic Mixture in Rats est apparu en premier sur ETAP-LAB.

Anti-Diarrheal and Anti-Nociceptive Effects of a Hydroethanolic Leaf Extract of Walnut in Rats

Gregory — Mon, 19 Dec 2016 09:30:50 +0000

Juglans regia L. (walnut) is a plant traditionally used for the treatment of diarrhea. We investigated the antidiarrheal effects of a hydroethanolic leaf extract (HLE) of J. regia against castor oil-induced diarrhea in rats after screening phenolic compounds in the extract. J. regia HLE (0.5, 1, and 2 g/kg by gavage) produced a dose-dependent delay in the onset of diarrhea compared to the vehicle. It also significantly reduced the number of diarrheal feces, fresh weight and water content of the feces, body weight loss and pain at the two highest doses. Loperamide was effective in inhibiting diarrhea and body weight loss but failed to reduce pain. Our findings show that J. regia HLE has a beneficial effect on diarrhea symptoms and associated pain suggesting that it could be an interesting alternative to standard anti-motility drugs. Flavonoids and hydroxycinnamic acids detected in the extract might explain the effects observed.

Link to the article

L’article Anti-Diarrheal and Anti-Nociceptive Effects of a Hydroethanolic Leaf Extract of Walnut in Rats est apparu en premier sur ETAP-LAB.

Benefits of Preventive Administration of Chlorella sp. on Visceral Pain and Cystitis Induced by a Single Administration of Cyclophosphamide in Female Wistar Rat.

Gregory — Tue, 21 Jun 2016 12:52:38 +0000

Chlorella sp. is a green microalgae containing nutrients, vitamins, minerals, and chlorophyll. In some communities, Chlorella sp. is a traditional medicinal plant used for the management of inflammation-related diseases. In a rat model, ROQUETTE Chlorella sp. (RCs) benefits were investigated on visceral pain and associated inflammatory parameters related to cystitis both induced by cyclophosphamide (CYP). RCs was orally administered every day from day 1-16 (250 and 500 mg/kg body weight). Six hours after an intraperitoneal injection of 200 mg/kg body weight of CYP, body temperature, general behavior, food intake, and body weight were recorded. Twenty-four hours after CYP injection, rats were tested in two behavioral tests, an open field and the aversive light stimulus avoidance conditioning test, to evaluate the influence of pain on general activity and learning ability of rats. After euthanasia, bladders were weighed, their thickness was scored, and the urinary hemoglobin was measured. RCs orally administered at the two dosages significantly reduced visceral pain and associated inflammatory parameters related to cystitis both induced by CYP injection, and improved rat behavior. To conclude, RCs demonstrated beneficial effects against visceral pain and cystitis.

L’article Benefits of Preventive Administration of Chlorella sp. on Visceral Pain and Cystitis Induced by a Single Administration of Cyclophosphamide in Female Wistar Rat. est apparu en premier sur ETAP-LAB.

Behavioral toxicity and physiological changes from repeated exposure to fluorene administered orally or intraperitoneally to adult male Wistar rats: A dose-response study

Gregory — Fri, 27 May 2016 09:33:42 +0000

Fluorene is one of the most abundant polycyclic aromatic hydrocarbons (PAHs) in the environment by reason of its high volatility. Demonstrated to be a neurotoxicant through inhalation, it was also identified as a contributive PAH to food contamination. Since no data are available on its oral neurotoxicity, the purpose of the present study was to assess the behavioral and physiological toxicity of repeated oral administration of fluorene to adult Wistar male rats. Animals were daily treated with fluorene at 1, 10 or 100mg/kg/day for 28 consecutive days. Administration was intraperitoneal (i.p.) or oral (p.o.) to evaluate the influence of the route of exposure on fluorene toxicity. Following this period of treatment, animals in both groups were subjected to similar cognitive evaluations, namely anxiety (elevated-plus maze), locomotor activity (open-field) and learning and memory abilities (eight-arm maze and avoidance test of an aversive light stimulus), as well as physiological measurements. The behavioral testing occurred from the 28th to the 60th day of the experiment during which fluorene treatment continued uninterrupted. At the end of this period, the concentration levels of fluorene and of three of its monohydroxylated metabolites in blood and brain were determined using a GC-MS/MS method. The results demonstrated a reduction in rat anxiety level at the lowest doses administered (1 and 10mg/kg/day) regardless of the treatment route, whereas locomotor activity and learning abilities remained unchanged. Moreover, a less significant weight gain was noticed in animals i.p.- and p.o.-treated with 100mg/kg/day during the 28-day period of treatment, which, upon comparison with the three other groups, induced a body weight gap that was maintained throughout the experiment. Significant increases in relative liver weight were also observed in a dose-dependent manner in orally treated rats and only in animal treated i.p. with 100mg/kg/day. According to the dose, higher concentration levels of fluorene and its monohydroxylated metabolites were measured in blood and brain compartments of i.p.-treated rats compared to p.o.-treated animals. In conclusion, fluorene reduced the anxiety level of rats related to dose, treatment route, duration of exposure and blood concentration levels of metabolites.

L’article Behavioral toxicity and physiological changes from repeated exposure to fluorene administered orally or intraperitoneally to adult male Wistar rats: A dose-response study est apparu en premier sur ETAP-LAB.

Evidence for an antihypertensive effect of a land snail (Helix aspersa) by-product hydrolysate – Identification of involved peptides

Gregory — Tue, 24 May 2016 09:22:30 +0000

The antihypertensive potential of a land snail by-product hydrolysate (SBH), obtained after an industrial treatment of the raw material, was studied in vitro and in vivo. The ACE inhibitory activity of SBH was characterised by an IC50 value of 23 µg⋅mL−1, which was not affected by in vitro digestion. SBH enhanced the Caco-2 intestinal cell metabolic activity and did not induce any toxicity in Wistar rats. The partial purification of SBH led to the obtainment of an active fraction characterised by an IC50 of 0.007 µg⋅mL−1. The sequences of the 17 most abundant peptides of the fraction were identified by LC/MS/MS analysis. Seven of them (YG, YA, VY, SF, FG, GF and VW) are known ACE inhibitory peptides. Finally, in vivo study on SHR rats showed that SBH significantly reduced systolic blood pressure. SBH represents therefore a new candidate as an ingredient for the design of functional foods against hypertension.

Link to the article

L’article Evidence for an antihypertensive effect of a land snail (Helix aspersa) by-product hydrolysate – Identification of involved peptides est apparu en premier sur ETAP-LAB.

Negative effect of clenbuterol on physical capacities and neuromuscular control of muscle atrophy in adult rats.

Gregory — Fri, 22 Jan 2016 09:43:09 +0000

INTRODUCTION: Clenbuterol has been used to alleviate chronic obstructive pulmonary disease and elicit an anabolic response in muscles. The aim of this study was to determine the influence of muscle mass variation on physical capacities in rats.

METHODS: The left hindlimbs of Wistar rats were immobilized for 20 days in plantarflexion with a splint and then remobilized for 16 days. The effect of a non-myotoxic dose of clenbuterol during the immobilization period was evaluated. Physical capacities were coordination, free locomotion, grip strength, and bilateral deficit.

RESULTS: Immobilization induced a loss of muscle mass, coordination, and strength without any effect on free locomotion. The positive anabolic effect of clenbuterol did not prevent a loss of physical capacities resulting from immobilization.

CONCLUSIONS: Muscle mass correlated strongly with coordination and isometric strength in untreated rats. Anabolic effect, fiber phenotype modification, and perturbation in neuromuscular communication with clenbuterol improved muscle mass, but it altered physical capacities.

L’article Negative effect of clenbuterol on physical capacities and neuromuscular control of muscle atrophy in adult rats. est apparu en premier sur ETAP-LAB.

In Situ Microparticles Loaded with S-Nitrosoglutathione Protect from Stroke

Gregory — Mon, 11 Jan 2016 09:31:02 +0000

Treatment of stroke, especially during the first hours or days, is still lacking. S-nitrosoglutathione (GSNO), a cerebroprotective agent with short life time, may help if administered early with a sustain delivery while avoiding intensive reduction in blood pressure. We developed in situ forming implants (biocompatible biodegradable copolymer) and microparticles (same polymer and solvent emulsified with an external oily phase) of GSNO to lengthen its effects and allow cerebroprotection after a single subcutaneous administration to Wistar rats. Arterial pressure was recorded for 3 days (telemetry, n = 14), whole-blood platelet aggregation up to 13 days (aggregometry, n = 58), and neurological score, cerebral infarct size and edema volume for 2 days after obstruction of the middle cerebral artery by autologous blood clots (n = 30). GSNO-loaded formulations (30 mg/kg) induced a slighter and longer hypotension (-10 vs. -56 ± 6 mmHg mean arterial pressure, 18 h vs. 40 min) than free GSNO at the same dose. The change in pulse pressure (-50%) lasted even up to 42 h for microparticles. GSNO-loaded formulations (30 mg/kg) prevented the transient 24 h hyper-aggregability observed with free GSNO and 7.5 mg/kg-loaded formulations. When injected 2 h after stroke, GSNO-loaded microparticles (30 mg/kg) reduced neurological score at 24 (-62%) and 48 h (-75%) vs. empty microparticles and free GSNO 7.5 mg/kg and, compared to free GSNO, divided infarct size by 10 and edema volume by 8 at 48 h. Corresponding implants reduced infarct size and edema volume by 2.5 to 3 times. The longer (at least 2 days) but slight effects on arterial pressures show sustained delivery of GSNO-loaded formulations (30 mg/kg), which prevent transient platelet hyper-responsiveness and afford cerebroprotection against the consequences of stroke. In conclusion, in situ GSNO-loaded formulations are promising candidates for the treatment of stroke.

L’article In Situ Microparticles Loaded with S-Nitrosoglutathione Protect from Stroke est apparu en premier sur ETAP-LAB.

Oral and Topical Administration of ROQUETTE Schizochytrium sp. Alleviate Skin Inflammation and Improve Wound Healing in Mice.

Gregory — Mon, 21 Dec 2015 09:21:57 +0000

The human body is constantly exposed to the risk of traumatic lesions. ROQUETTE Schizochytrium sp. (SCs) is a marine microalgae containing large amounts of health-valuable nutrients, more particularly polyunsaturated fatty acids such as docosahexaenoic acid. SCs was investigated by oral administration (125, 250 and 500 mg/kg) and cutaneous application (2.5, 5.0 and 10.0%) to evaluate its impact in two dermatological disorder models in mice: skin inflammation and wound healing. For skin inflammation, it was administered during 14 days starting one week before the induction of chronic skin inflammation by repeated cutaneous application of 12-O-tetradecanoylphorbol 13-acetate (TPA). For wound healing the microalgae was administered after incisional wound healing of the skin until complete wound healing. Results indicated that oral and topical administrations of the two higher doses of SCs had significant effects on macroscopic score of skin inflammation. It had also efficient effect on healing process and duration of wound healing with a dose-response by oral administration and a maximal effect observed from the lowest to the highest dose by topical application. These findings suggest that administration of SCs by both oral and topical routes appeared to have beneficial effects on skin lesions.

L’article Oral and Topical Administration of ROQUETTE Schizochytrium sp. Alleviate Skin Inflammation and Improve Wound Healing in Mice. est apparu en premier sur ETAP-LAB.

Publication: “Temporal hemodynamic and histological changes in a rat model sugen-induced PAH.”

agavtheve — Fri, 30 Oct 2015 09:04:00 +0000

Research publication titled: “Temporal hemodynamic and histological changes in a rat model sugen-induced PAH.” V. Girod et al. SYNCROSOME. European Respiratory Journal 2015 46(suppl 59): PA4910

Read the full study here/DOI: https://doi.org/10.1183/13993003.congress-2015.PA4910

Authors:

Vincent Girod, Audrey Bourdet, Sandra Robelet, Adeline Bouzereau, Delphine Revy

Affiliations : In Vivo Pharmacology, SYNCROSOME, Marseille, France

Abstract
Pulmonary arterial hypertension (PAH) is a progressive fatal disease characterized by a vascular remodeling of small pulmonary arteries leading to an increased right ventricular (RV) pressure and ultimately to RV failure. Treatments currently available do not cure the disease and new therapeutic strategies are needed. This involves the use of relevant animal models

The sugen (Su) model combines the administration of a vascular endothelial growth factor receptor blocker to a sequential exposure to hypoxia (Hx) and normoxia (Nx). Unlike the monocrotaline and hypoxia-induced PAH models, animals exposed to SuHxNx develop severe PAH with complex pulmonary vascular changes. However, very little data is available regarding temporal evolution of the disease, especially the appearance of plexiform lesions. The present work aimed at characterizing the progression of the disease over time using different approaches.

Rats were treated with Su, exposed to Hx and maintained in Nx up to 10 weeks. RV pressure and hypertrophy were then measured and histological analysis of small pulmonary arteries was performed.

As expected, treatment with Su associated with an exposure to Hx+Nx worsened Hx-induced PAH (RVSP>70 mmHg) with severe medial hypertrophy and intimal proliferation. The extent of vascular remodeling increased with the duration of Nx to reach a maximum after 3 weeks with 50% of the analysed vessels partially or totally occluded. Finally, plexiform lesions occurred immediately after the end of Hx and affected 35% of the small pulmonary arteries after 3 weeks of Nx. Death also occurred after 5 weeks.

Exposure to Su+Hx with 3 weeks of Nx could provide a relevant model for the development of new treatments for PAH.

L’article Publication: “Temporal hemodynamic and histological changes in a rat model sugen-induced PAH.” est apparu en premier sur ETAP-LAB.

Shaping mycolactone for therapeutic use against inflammatory disorders

Gregory — Wed, 03 Jun 2015 11:07:50 +0000

Inflammation adversely affects the health of millions of people worldwide, and there is an unmet medical need for better anti-inflammatory drugs. We evaluated the therapeutic interest of mycolactone, a polyketide-derived macrolide produced by Mycobacterium ulcerans. Bacterial production ofmycolactone in human skin causes a combination of ulcerative, analgesic, and anti-inflammatory effects. Whereas ulcer formation is mediated by the proapoptotic activity of mycolactone on skin cells via hyperactivation of Wiskott-Aldrich syndrome proteins, analgesia results from neuronal hyperpolarization via signaling through angiotensin II type 2 receptors. Mycolactone also blunts the capacity of immune cells to produceinflammatory mediators by an independent mechanism of protein synthesis blockade. In an attempt to isolate the structural determinants ofmycolactone‘s immunosuppressive activity, we screened a library of synthetic subunits of mycolactone for inhibition of cytokine production by activated T cells. The minimal structure retaining immunosuppressive activity was a truncated version of mycolactone, missing one of the two core-branched polyketide chains. This compound inhibited the inflammatory cytokine responses of human primary cells at noncytotoxic doses and bound to angiotensin II type 2 receptors comparably to mycolactone in vitro. Notably, it was considerably less toxic than mycolactone in human primary dermal fibroblasts modeling ulcerative activity. In mouse models of human diseases, it conferred systemic protection against chronic skin inflammation and inflammatory pain, with no apparent side effects. In addition to establishing the anti-inflammatory potency of mycolactone in vivo, our study therefore highlights the translational potential of mycolactone core-derived structures as prospective immunosuppressants.

L’article Shaping mycolactone for therapeutic use against inflammatory disorders est apparu en premier sur ETAP-LAB.

Benefits of oral and topical administration of ROQUETTE Chlorella sp. on skin inflammation and wound healing in mice

Gregory — Mon, 15 Dec 2014 10:14:06 +0000

The human body is constantly exposed to the risk of traumatic lesions. Chlorella is a green microalgae enriched with nutrients, vitamins, minerals and chlorophyll. In some communities, Chlorella is a traditional medicinal plant used for the management of inflammation-related diseases. ROQUETTE Chlorella sp. (RCs) was investigated by oral administration (125, 250 and 500 mg/kg) and cutaneous application (2.5, 5.0 and 10.0%) to evaluate its impact in two dermatological disorder models in mice: skin inflammation and wound healing. For skin inflammation, it was administered during 14 days starting one week before the induction of chronic skin inflammation by repeated cutaneous application of 12-Otetradecanoylphorbol 13-acetate (TPA). For wound healing the microalgae was administered by topical application after scarification of the skin until complete wound healing. Results indicated that oral and topical administrations of the two higher doses of RCs had significant effects on macroscopic score of skin inflammation with an efficient effect on microscopic score with cutaneous application. The microalgae had also efficient effect on healing process and duration of wound healing for both administration routes and particularly at the two highest doses of RCs. These findings suggest that administration of RCs by both oral and topical routes appeared to have beneficial effects on skin lesions.

L’article Benefits of oral and topical administration of ROQUETTE Chlorella sp. on skin inflammation and wound healing in mice est apparu en premier sur ETAP-LAB.

Behavioral and neurochemical effects of dietary methyl donor deficiency combined with unpredictable chronic mild stress in rats

Gregory — Mon, 01 Dec 2014 11:06:57 +0000

Methyl donor deficiencies and chronic stress cause depression independently, but their interaction has never been thoroughly evaluated. In our study, methyl donor deficient diet and chronic stress condition consisted respectively of a B2, B9, B12, and choline-free diet and a chronic mild stress procedure. Rats were randomly assigned to six groups with three “diet” conditions (free-feeding, pair-fed and methyl donor deficient diet) and two “stress” conditions (no-stress and stress) and were evaluated in the open-field, the elevated plus-maze and the forced swimming test. After the behavioral evaluation, corticosterone and homocysteine plasma levels were measured and dopamine, DOPAC, serotonin, 5HIAA concentrations were evaluated in several brain areas. Rats given a methyl donor deficient diet for 11 weeks causing elevated plasma homocysteine levels were compared to pair-fed and free-feeding rats with or without unpredictable chronic mild stress. Regardless of stress environmental conditions, the methyl donor deficient diet decreased plasma corticosterone levels and caused disinhibition in the elevated plus-maze condition relative to both control groups. However, stress potentiated the effects of the deficient regimen on rearing in the open-field and climbing in the forced swim test. The dietary changes involved in behavior and plasma corticosterone could be caused by homocysteine-induced decreases in dopamine and 5-hydroxytryptamine metabolites in selective brain regions and it can be noted that regardless of stress-conditions, methyl donor deficient diet decreases DOPAC/dopamine and 5HIAA/serotonin ratios in striatum and hypothalamus and selectively 5HIAA/serotonin ratio in the sensorimotor cortex. Our experimental data is particularly relevant in the context of neuropsychiatric disorders frequently associated with folate deficiency and hyperhomocysteinemia.

L’article Behavioral and neurochemical effects of dietary methyl donor deficiency combined with unpredictable chronic mild stress in rats est apparu en premier sur ETAP-LAB.

Skin Repair Properties of d-Limonene and Perillyl Alcohol in Murine Models

Gregory — Mon, 27 Oct 2014 11:05:48 +0000

The orange-peel derived terpene d-Limonene, probably through its metabolite, perillyl alcohol (POH), has been reported to have tissue-repair properties. Two murine models of respectively 12-O-Tetradecanoylphorbol-13-Acetate (TPA)-induced dermatitis and mechanical skin lesion were used here to assess the efficacy of d-Limonene or POH applied topically. Macroscopic and microscopic evaluation of skin lesions was performed as well as that of P-selectin expression, together with measurements of serum concentrations of IL-1β, IL-6 and TNF-αin the first model. Healing and angiogenesis around the scar were examined in the second model. Because differences in angiogenesis were noted, the effect of both d-Limonene and POH was further tested on an in vitro model of endothelial microtubules formation. Both d-Limonene and POH reduced the severity and extension of TPA-induced skin lesions with significantly lowered macroscopic and microscopic scores (p<0.04 in both cases). Moreover, the expression of P-selectin induced by TPA was abrogated by POH and significantly lower serum concentrations of IL-6 and TNF-α were observed in d-Limonene- and POH-treated mice (p<0.04 and 0.03). In the second model, tissue regeneration was improved, especially by POH, and was clearly associated with reduced neovascularization. This surprising anti-angiogenic effect was confirmed in the matrigel model of endothelial microtubules formation. These studies show that d-Limonene and POH demonstrate significant anti-inflammatory effects in murine dermal inflammation and wound-healing. The decreased systemic cytokine production as well as a consistent inhibition of endothelial P-selectin expression and neo-vascularization induced by these terpenic compounds contribute to their healing effects on the epidermal barrier.

L’article Skin Repair Properties of d-Limonene and Perillyl Alcohol in Murine Models est apparu en premier sur ETAP-LAB.

Anti-stress effects of d-Limonene and its metabolite perillyl alcohol

Gregory — Wed, 15 Oct 2014 19:02:11 +0000

Stress is closely linked by its biological mechanisms to inflammation and by its consequences to accelerated aging. Stress triggers a hormonal response along the hypothalamus-pituitary-adrenal (HPA) axis, liable to disrupt the ortho / parasympathetic balance essential for a harmonious life. Proper nutrition and adequate physical activity, by limiting the harmful influence of stress, play important roles to avoid developing disease and to promote healthy aging. d-Limonene, a monoterpene shown to reduce inflammatory parameters in several pre-clinical and clinical models, could also develop an anti-stress action by altering ortho / parasympathetic parameters as well as central neurotransmitter functions. Here we report on a rat model, where a functional observational battery (FOB) was performed, submitting animals to non-pathological stress. d-Limonene or its metabolite perillyl alcohol (POH) were administered per os at a dose of 10mg/kg. FOB tests were performed one hour before gavage then at 60, 120 and 180 minutes. These tests confirmed the stressed status of control rats fed vehicle. Conversely, a series of parameters were significantly less disturbed in treated rats who retained a better activity and displayed less sings of stress. These effects were more pronounced and sustained after ingestion of d-Limonene than POH, suggesting the role of endogeneous metabolization of the terpene. These studies show that d-Limonene exerts, through its metabolite POH, a significant anti-stress action measurable by behavioral and physiologic parameters under the influence of the nervous system. In addition to its anti-inflammatory effects, a beneficial role for d-Limonene as diet supplement could thus be claimed as an anti-stress substance.

L’article Anti-stress effects of d-Limonene and its metabolite perillyl alcohol est apparu en premier sur ETAP-LAB.

Preventive effects of lignan extract from flax hulls on experimentally induced benign prostate hyperplasia

Gregory — Thu, 24 Jul 2014 12:29:21 +0000

Consumption of diet rich in lignans may decrease the risk of some chronic hormonal conditions such as benign prostatic hyperplasia (BPH). This study investigated whether a lignan-rich extract from flaxseed hulls, LinumLife EXTRA (LLE), could prevent BPH using the testosterone propionate (TP)-induced BPH rat model. Male Wistar-Unilever rats were randomly divided into four groups of 12 rats each: a negative control group fed with control diet and receiving daily subcutaneous injections of corn oil without TP, and three groups fed with control diet (positive control), diet containing 0.5% LLE (LLE 0.5) or 1.0% LLE (LLE 1.0) and receiving daily subcutaneous injections of TP in corn oil. Treatments with diets started 2 weeks before the induction of BPH and were carried out for 5 consecutive weeks. The influence of TP and LLE on body weight (BW), food and water consumptions, and enterolactone (ENL) levels in serum and urine of rats was examined at the end of the 5-week treatment period. TP significantly diminished the mean body weight gain (MBWG) of positive control rats and their food and water consumptions while LLE reduced significantly this MBWG reduction in a dose-dependent manner. The lignan-rich extract significantly inhibited TP-induced prostate size ratio (prostate weight/rat BW) increase in comparison with positive controls (P<.001). This effect was dose dependent. Higher serum and urine levels of ENL correlated well with the dose of extract provided to rats. It was concluded that the lignan-rich flaxseed hull extract prevented the TP-induced BPH indicating it might be beneficial in the prevention of BPH.

L’article Preventive effects of lignan extract from flax hulls on experimentally induced benign prostate hyperplasia est apparu en premier sur ETAP-LAB.

Methylphenidate-risperidone combination in child psychiatry: A retrospective analysis of 44 cases

Gregory — Tue, 24 Jun 2014 09:52:16 +0000

INTRODUCTION: Psychotimulant-antipyschotic combinations are frequently used in child psychiatry, but have been rarely described in the literature.

METHOD AND PATIENTS: We propose here a retrospective study of 44 children who received the combination methylphenidate (MPH)-risperidone (RIS). The sample is composed of children who received either MPH (n=28) or RIS (n=16) as primary treatment. A vast majority of the children had a comorbid attention deficit hyperactivity disorder (ADHD) diagnosis.

RESULTS: For over 60% of patients, regardless of their initial monotherapy, bitherapy decreased the symptoms of ADHD and conduct disorder, sleep disorders and anxiety. Concerning the safety of the bitherapy, a compensation effect on weight gain and appetite was respectively observed in 70% and 50% of patients. Even though iatrogenic tachycardia can be encountered with both drugs, it has never been reported when they are associated and we have reported a total of 3 cases in our study. We have also observed a case of dyskinesia resolved with the discontinuation of the treatment.

DISCUSSION/CONCLUSION: MPH-RIS bitherapy appears to be particularly effective in ADHD with conduct disorder symptoms. Although tolerance may limit its use, the benefit/risk ratio seems favourable for a number of children.

L’article Methylphenidate-risperidone combination in child psychiatry: A retrospective analysis of 44 cases est apparu en premier sur ETAP-LAB.

p-Coumaric acid activates the GABA-A receptor in vitro and is orally anxiolytic in vivo.

Gregory — Mon, 24 Mar 2014 09:30:24 +0000

The increasing prevalence and social burden of subclinical anxiety in the western world represents a significant psychosocial and financial cost. Consumers are favouring a more natural and nonpharmacological approach for alleviating the effects of everyday stress and anxiety. The gamma-aminobutyric acid (GABA) receptor is the primary mediator of central inhibitory neurotransmission, and GABA-receptor agonists are well known to convey anxiolytic effects. Using an in vitro screening approach to identify naturally occurring phytochemical GABA agonists, we discovered the plant secondary metabolite p-coumaric acid to have significant GABAergic activity, an effect that could be blocked by co-administration of the specific GABA-receptor antagonist, picrotoxin. Oral administration of p-coumaric acid to rodents induced a significant anxiolytic effect in vivo as measured using the elevated plus paradigm, in line with the effects of oral diazepam. Given that p-coumaric acid is reasonably well absorbed following oral consumption in man and is relatively nontoxic, it may be suitable for the formulation of a safe and effective anxiolytic functional food.

L’article p-Coumaric acid activates the GABA-A receptor in vitro and is orally anxiolytic in vivo. est apparu en premier sur ETAP-LAB.

Structure- Activity Relationship Study and Function-Based Petidomimetic Design of Human Opiorphin with Improved Bioavailability Property and Unaltered Analgesic Activity

Gregory — Mon, 16 Dec 2013 13:21:21 +0000

Human opiorphin inhibits enkephalin-inactivating ectopeptidases to produce analgesic and antidepressant-like effects in standard murine models via activation of µ and/or δ opioid pathways. It is an endogenous peptide regulator of enkephalin bioavailability. Opiorphin molecule, a QRFSR-peptide, is thus a promising prototype for the design of an improved class of analgesics. The major limitation on the clinical use of peptide drugs is their rapid degradation by circulating peptidases. Our goal was, therefore, to search for functional derivatives of opiorphin with improved metabolic stability. In order to identify the functional amino acid groups required for opiorphin inhibitory potency toward both AP-N and NEP human ectopeptidases, we used the Structure-Activity Relationship (SAR) method. From this data, a series of opiorphin derivatives was designed and selected. The best performing compound then underwent a complete metabolic profile using in vitro kinetic models. Finally, its safety profile relative to the native peptide as well as its efficacy in an in vivo rat model was evaluated. We demonstrated a tight structural selectivity in the functional interaction of opiorphin with both human NEP and AP-N targets by SAR studies. Nevertheless, we found that the addition of an N-terminal Zn-chelating group, a Cys-thiol group and the replacement of the first labile peptide bond by a polyethylene surrogate, a [CH2 ] 6 linker,and, finally, the substitution of Ser4 by Ser-O-[CH2 ] 8 , results in a high performing C-[(CH2 )6 ]-QRF[S-O-[CH2 ] 8 ]-R peptidomimetic product. This designed opiorphin analog shows reinforced inhibitory potency toward human AP-N activity (more than 10-fold increase) and NEP activities (more than 40-fold increase) relative to the QRFSR native peptide. It also has increased metabolic stability in human plasma and yet retains full analgesic activity in the behavioral formalin-induced rat pain model. C-[(CH2 )6 ]-QRF[S-O-[CH2 ] 8 ]-R thus represents a very attractive and promising analgesic drug-candidate.

Link to the article

L’article Structure- Activity Relationship Study and Function-Based Petidomimetic Design of Human Opiorphin with Improved Bioavailability Property and Unaltered Analgesic Activity est apparu en premier sur ETAP-LAB.

Oral administration of d-limonene controls inflammation in rat colitis and displays anti-inflammatory properties as diet supplementation in humans

Gregory — Mon, 01 Jul 2013 19:01:21 +0000

AIMS:

To further explore the anti-inflammatory properties of d-Limonene.

MAIN METHODS:

A rat model was used to compare evolution of TNBS (2,5,6-trinitrobenzene sulfonic acid)-induced colitis after oral feeding with d-Limonene compared to ibuprofen. Peripheral levels of TNF-α (Tumor Necrosis Factor alpha) were assessed in all animals. Cell cultures of fibroblasts and enterocytes were used to test the effect of d-Limonene respectively on TNFα-induced NF-κB (nuclear factor-kappa B) translocation and epithelial resistance. Finally, plasmatic inflammatory markers were examined in an observational study of diet supplementation with d-Limonene-containing orange peel extract (OPE) in humans.

KEY FINDINGS:

Administered per os at a dose of 10mg/kg p.o., d-Limonene induced a significant reduction of intestinal inflammatory scores, comparable to that induced by ibuprofen. Moreover, d-Limonene-fed rats had significantly lowered serum concentrations of TNF-α compared to untreated TNBS-colitis rats. The anti-inflammatory effect of d-Limonene also involved inhibition of TNFα-induced NF-κB translocation in fibroblast cultures. The application of d-Limonene on colonic HT-29/B6 cell monolayers increased epithelial resistance. Finally, inflammatory markers, especially peripheral IL-6, markedly decreased upon OPE supplementation of elderly healthy subjects submitted or not to 56 days of dietary supplementation with OPE.

SIGNIFICANCE:

In conclusion, d-Limonene indeed demonstrates significant anti-inflammatory effects both in vivo and in vitro. Protective effects on the epithelial barrier and decreased cytokines are involved, suggesting a beneficial role of d-Limonene as diet supplement in reducing inflammation.

L’article Oral administration of d-limonene controls inflammation in rat colitis and displays anti-inflammatory properties as diet supplementation in humans est apparu en premier sur ETAP-LAB.

Mining the brain metabolome to understand behavioural disruptions induced in mouse fed Hypochoeris radicata (L.), a neurotoxic plant for horse

Gregory — Fri, 28 Jun 2013 11:09:28 +0000

Mining the brain metabolome to understand behavioural disruptions induced in mouse fed Hypochoeris radicata (L.), a neurotoxic plant for horse. C57BL/6J mice orally exposed to 9% H. radicata (HR) are metabolically competent laboratory animals which can be used as model of Australian stringhalt, a neurological horse disease induced by HR ingestion. So, the present study was conducted to assess the brain metabolome and the behavioural performances of mice fed with a 9%-HR-based diet for 21 days. By the end of the period of exposure, mice were investigated for motor activity and coordination, anxiety level, learning and memory performances, social behaviour and rewarding properties of for the plant. Thus, the animals were sacrificed and the brain metabolome was studied using (1)H NMR spectroscopy. HR-exposed mice displayed a motor hyperactivity in several tasks, a less resignation in the forced swimming test, and paradigm place preference for the plant. A bootstrap-based regularized canonical analysis performed on merged behavioural and metabolic datasets showed a clear relationship in HR-treated mice between an increase in cerebral scyllo-inositol, an increased motor activity, and seemingly rewarding properties of HR. These results underlie the interest of such a dual approach to characterize functional end-points of a pathophysiological model of the Australian stringhalt in equine species.

L’article Mining the brain metabolome to understand behavioural disruptions induced in mouse fed Hypochoeris radicata (L.), a neurotoxic plant for horse est apparu en premier sur ETAP-LAB.

Effects of TLC-Ag dressings on skin inflammation

Gregory — Sat, 01 Jun 2013 11:08:38 +0000

The TLC-Ag dressings, a combination of technology lipido-colloid and silver salts, are used to promote healing in wounds with risks or signs of local infection, thanks to the antimicrobial properties of the silver salts. Nanocrystalline silver dressings containing nanocrystalline silver, also used to improve wound healing, present both antimicrobial and anti-inflammatory effects. The aim of this study was to investigate the anti-inflammatory effects of TLC-Ag dressings in a model of chronic skin inflammation induced by repeated application of 12-O-tetradecanoylphorbol-13-acetate to the skin of hairless mice, in comparison with TLC dressing, Silcryst nanocrystalline dressing, desonide cream 0.05%, a corticoid cream used as positive control, and gauze. Daily treatments of the mice began 7 days after the start of induction of chronic skin inflammation and lasted for 7 days. A macroscopic score was performed daily during the treatment period until the mice killing on day 15 and skin samples were taken for histopathological analysis. TLC-Ag reduced significantly the macroscopic score of chronic skin inflammation from day 10 in comparison with gauze and TLC dressing, similarly to Silcryst nanocrystalline dressing and desonide cream, which presented the best anti-inflammatory effects. No significant differences were observed between TLC dressing and gauze. TLC-Ag reduced significantly the microscopic score of chronic skin inflammation in comparison with TLC dressing and gauze, similarly to Silcryst nanocrystalline dressing but significantly less than desonide cream. These results demonstrate that TLC-Ag dressings present significant anti-inflammatory effects on chronic skin inflammation. They can improve wound healing, due to both the antimicrobial and anti-inflammatory properties.© 2013 Japanese Dermatological Association.

L’article Effects of TLC-Ag dressings on skin inflammation est apparu en premier sur ETAP-LAB.

Enhanced cognitive function and antidepressant-like effects after krill oil supplementation in rats

Gregory — Tue, 01 Jan 2013 19:06:12 +0000

BACKGROUND:

The purpose of the study was to evaluate the effects of krill oil (KO) on cognition and depression-like behaviour in rats.

METHODS:

Cognition was assessed using the Aversive Light Stimulus Avoidance Test (ALSAT). The Unavoidable Aversive Light Stimulus (UALST) and the Forced Swimming Test (FST) were used to evaluate the antidepressant-like effects of KO. Imipramine (IMIP) was used as the antidepressant reference substance.

RESULTS:

After 7 weeks of KO intake, both males and females treated with KO were significantly better in discriminating between the active and the inactive levers in the ALSAT from day 1 of training (p<0.01). Both KO and IMIP prevented resignation/depression on the third day in the UALST. Similarly, a shorter immobility time was observed for the KO and IMIP groups compared to the control in the FST (p<0.001). These data support a robust antidepressant-like potential and beneficial cognitive effect of KO. Changes in expression of synaptic plasticity-related genes in the prefrontal cortex and hippocampus were also investigated. mRNA for brain-derived neurotrophic factor (Bdnf) was specifically upregulated in the hippocampus of female rats receiving 7 weeks of KO supplementation (p=0.04) and a similar trend was observed in males (p=0.08). Males also exhibited an increase in prefrontal cortex expression of Arc mRNA, a key protein in long-term synaptic plasticity (p=0.05). IMIP induced clear effects on several plasticity related genes including Bdnf and Arc.

CONCLUSIONS:

These results indicate that active components (eicosapentaenoic acid, docosahexaenoic acid and astaxanthin) in KO facilitate learning processes and provide antidepressant-like effects. Our findings also suggest that KO might work through different physiological mechanisms than IMIP.

L’article Enhanced cognitive function and antidepressant-like effects after krill oil supplementation in rats est apparu en premier sur ETAP-LAB.

Effects of ID-alG™ on weight management and body fat mass in high-fat-fed rats

Gregory — Tue, 01 May 2012 19:05:21 +0000

Seaweed extract of Ascophyllum nodosum, ID-alG™, was evaluated for its chronic effects on weight management in high-fat-fed Sprague-Dawley rats. ID-alG™ was orally administered daily during 9 weeks at doses of 40 and 400 mg/kg/day with fat-enriched diet (FED) in comparison with two control groups consuming standard diet (negative control) or FED (positive control) and orally treated with vehicle. Body weight, percentage of body fat mass and lipid parameters were measured. After 9 weeks, the oral administration of ID-alG™ at both doses decreased significantly the mean body weight gains (MBWG) of rats submitted to the FED in comparison to the positive control (-6.8% and -11.8%). ID-alG™ at both doses improved significantly the MBWG of rats and decreased significantly the percentage of body fat mass of rats (-9.8% and -19.0%), in comparison to the positive control. In the same way, the triglyceride blood level was also significantly improved for the dose of 400 mg/kg/day (-30.6% vs. +49.9% for the positive control); and the dose of 40 mg/kg/day just lead to a trend. Moreover, in both controls and ID-alG™-treated groups, total cholesterol, LDL and HDL blood levels were not modified. The seaweed extract of Ascophyllum nodosum, ID-alG™, demonstrated beneficial effects on weight management of rats submitted to a high-fat diet.

L’article Effects of ID-alG™ on weight management and body fat mass in high-fat-fed rats est apparu en premier sur ETAP-LAB.

Context-dependent modulation of hippocampal and cortical recruitment during remote spatial memory retrieval

Gregory — Sun, 01 Apr 2012 19:04:31 +0000

According to systems consolidation, as hippocampal-dependent memories mature over time, they become additionally (or exclusively) dependent on extra-hippocampal structures. We assessed the recruitment of hippocampal and cortical structures on remote memory retrieval in a performance-degradation resistant (PDR; no performance degradation with time) versus performance-degradation prone (PDP; performance degraded with time) context. Using a water-maze task in two contexts with a hidden platform and three control conditions (home cage, visible platform with or without access to distal cues), we compared neuronal activation (c-Fos imaging) patterns in the dorsal hippocampus and the medial prefrontal cortex (mPFC) after the retrieval of recent (5 days) versus remote (25 days) spatial memory. In the PDR context, the hippocampus exhibited greater c-Fos protein expression on remote than recent memory retrieval, be it in the visible or hidden platform group. In the PDP context, hippocampal activation increased at the remote time point and only in the hidden platform group. In the anterior cingulate cortex, c-Fos expression was greater for remote than for recent memory retrieval and only in the PDR context. The necessity of the mPFC for remote memory retrieval in the PDR context was confirmed using region-specific lidocaine inactivation, which had no impact on recent memory. Conversely, inactivation of the dorsal hippocampus impaired both recent and remote memory in the PDR context, and only recent memory in the PDP context, in which remote memory performance was degraded. While confirming that neuronal circuits supporting spatial memory consolidation are reorganized in a time-dependent manner, our findings further indicate that mPFC and hippocampus recruitment (i) depends on the content and perhaps the strength of the memory and (ii) may be influenced by the environmental conditions (e.g., cue saliency, complexity) in which memories are initially formed and subsequently recalled.

L’article Context-dependent modulation of hippocampal and cortical recruitment during remote spatial memory retrieval est apparu en premier sur ETAP-LAB.

Neurobehavioral and physiological effects of low doses of polubrominated diphenyl ether (PBDE)-99 in male adult rats

Gregory — Fri, 01 Jul 2011 19:10:04 +0000

Polybrominated diphenyl ethers (PBDEs) are flame retardants. Because of their high lipophilicity and persistence, PBDEs bioaccumulate in all abiotic and biological matrices. The aim of this study was to investigate the long-term neurobehavioral and physiological effects of exposure to environmental doses of PBDE-99 in adult rats. Rats received a daily administration of PBDE-99 for 90 days by oral gavage at 0.15, 1.5 and 15μg/kg, doses which are relevant of human exposure. Before and after the 90 days of exposure, behavioral tests including the open-field and the elevated plus-maze tests for locomotor activity and anxiety, and the Morris water maze for spatial learning were conducted. Physiological measures such as body weight, food and water consumption, organs weight, hepatic enzymes levels and PBDE-99 concentration in adipose tissue were also evaluated at the end of exposure. There was no effect on body weight, food and water consumption, organs weight, hepatic enzymes levels despite rising PBDE-99 concentration in adipose tissue with the doses tested. Moreover, there was no effect on locomotor activity and exploration, and spatial learning. Deleterious effects of PBDE-99 at high doses have often been highlighted in many studies after an acute dose whereas exposure during 90 days at realistic doses would have no significant effect in adult rats.

L’article Neurobehavioral and physiological effects of low doses of polubrominated diphenyl ether (PBDE)-99 in male adult rats est apparu en premier sur ETAP-LAB.

Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers

Gregory — Fri, 01 Jul 2011 19:03:26 +0000

Discover Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers:

L’article Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers est apparu en premier sur ETAP-LAB.

Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions

Gregory — Mon, 18 Apr 2011 12:29:36 +0000

The corollaries of the obesity epidemic that plagues developed societies are malnutrition and resulting biochemical imbalances. Low levels of essential n-3 polyunsaturated fatty acids (n-3 PUFAs) have been linked to neuropsychiatric diseases, but the underlying synaptic alterations are mostly unknown. We found that lifelong n-3 PUFAs dietary insufficiency specifically ablates long-term synaptic depression mediated by endocannabinoids in the prelimbic prefrontal cortex and accumbens. In n-3-deficient mice, presynaptic cannabinoid CB(1) receptors (CB(1)Rs) normally responding to endocannabinoids were uncoupled from their effector G(i/o) proteins. Finally, the dietary-induced reduction of CB(1)R functions in mood-controlling structures was associated with impaired emotional behavior. These findings identify a plausible synaptic substrate for the behavioral alterations caused by the n-3 PUFAs deficiency that is often observed in western diets.

L’article Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions est apparu en premier sur ETAP-LAB.

Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects

Gregory — Tue, 01 Mar 2011 19:09:08 +0000

In a previous clinical study, a probiotic formulation (PF) consisting of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (PF) decreased stress-induced gastrointestinal discomfort. Emerging evidence of a role for gut microbiota on central nervous system functions therefore suggests that oral intake of probiotics may have beneficial consequences on mood and psychological distress. The aim of the present study was to investigate the anxiolytic-like activity of PF in rats, and its possible effects on anxiety, depression, stress and coping strategies in healthy human volunteers. In the preclinical study, rats were daily administered PF for 2 weeks and subsequently tested in the conditioned defensive burying test, a screening model for anti-anxiety agents. In the clinical trial, volunteers participated in a double-blind, placebo-controlled, randomised parallel group study with PF administered for 30 d and assessed with the Hopkins Symptom Checklist (HSCL-90), the Hospital Anxiety and Depression Scale (HADS), the Perceived Stress Scale, the Coping Checklist (CCL) and 24 h urinary free cortisol (UFC). Daily subchronic administration of PF significantly reduced anxiety-like behaviour in rats (P < 0·05) and alleviated psychological distress in volunteers, as measured particularly by the HSCL-90 scale (global severity index, P < 0·05; somatisation, P < 0·05; depression, P < 0·05; and anger-hostility, P < 0·05), the HADS (HADS global score, P < 0·05; and HADS-anxiety, P < 0·06), and by the CCL (problem solving, P < 0·05) and the UFC level (P < 0·05). L. helveticus R0052 and B. longum R0175 taken in combination display anxiolytic-like activity in rats and beneficial psychological effects in healthy human volunteers.

L’article Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects est apparu en premier sur ETAP-LAB.

Efficacy of chronic antidepressant treatments in a new model of extreme anxiety in rats

Gregory — Sat, 01 Jan 2011 19:08:23 +0000

Animal models of anxious disorders found in humans, such as panic disorder and posttraumatic stress disorder, usually include spontaneous and conditioned fear that triggers escape and avoidance behaviors. The development of a panic disorder model with a learned component should increase knowledge of mechanisms involved in anxiety disorders. In our ethological model of extreme anxiety in the rat, forced apnea was combined with cold water vaporization in an inescapable situation. Based on the reactions of vehicle controls, behaviors involved in paroxysmic fear were passive (freezing) and active (jumping) reactions. Our results show that subchronic fluoxetine (5 mg/kg, IP, 21 days) and imipramine (10 mg/kg, IP, 14 days) administration alleviated freezing and jumping behaviors, whereas acute fluoxetine (1 mg/kg, IP) provoked opposite effects. Acute low dose of diazepam (1 mg/kg, IP) was not effective, whereas the higher dose of 3 mg/kg, IP, and clonazepam (1 mg/kg, IP) only had an effect on jumping. Paroxysmic fear generated in this experimental condition may therefore mimic the symptomatology observed in patients with anxiety disorders.

L’article Efficacy of chronic antidepressant treatments in a new model of extreme anxiety in rats est apparu en premier sur ETAP-LAB.

Systemically active human opiorphin is a potent yet non-addictive analgesic without drug tolerance effects

Gregory — Sun, 01 Aug 2010 19:07:21 +0000

Human opiorphin QRFSR-peptide protects enkephalins from degradation by human neutral endopeptidase (hNEP) and aminopeptidase-N (hAP-N) and inhibits pain perception in a behavioral model of mechanical acute pain (1). Here, using two other pain rat models, the tail-flick and the formalin tests, we assess the potency and duration of the antinociceptive action of opiorphin with reference to morphine. The occurrence of adverse effects with emphasis on the side-effect profile at equi-analgesic doses was compared. We demonstrate that opiorphin elicits minimal adverse morphine-associated effects, at doses (1-2 mg/kg, i.v.) that produce a comparable analgesic potency in both spinally controlled thermal-induced acute and peripheral chemical-induced tonic nociception. The analgesic response induced by opiorphin in the formalin-induced pain model preferentially requires activation of endogenous mu-opioid pathways. However, in contrast to exogenous mu-opioid agonists such as morphine, opiorphin, does not develop significant abuse liability or antinociceptive drug tolerance after subchronic treatment. In addition, anti-peristaltism was not observed. We conclude that opiorphin, by inhibiting the destruction of endogenous enkephalins, which are released according to the painful stimulus, activates restricted opioid pathways specifically involved in pain control, thus contributing to a greater balance between analgesia and side-effects than found with morphine. Therefore, opiorphin could give rise to new analgesics endowed with potencies similar to morphine but with fewer adverse effects than opioid agonists. Its chemical optimization, to generate functional derivatives endowed with better bioavailability properties than the native peptide, could lead to a potent class of physiological type analgesics.

L’article Systemically active human opiorphin is a potent yet non-addictive analgesic without drug tolerance effects est apparu en premier sur ETAP-LAB.

Human opiorphin is a naturally occurring antidepressant acting selectively on enkephalin-dependent delta-opioid pathways

Gregory — Tue, 01 Jun 2010 19:13:05 +0000

Human opiorphin protects enkephalins from degradation by human neutral endopeptidase and aminopeptidase-N and inhibits pain perception in various behavioral rodent models of pain via endogenous enkephalin-related activation of opioidergic pathways. In addition to pain control, endogenous opioid pathways are also implicated in the modulation of emotion-related behaviors. Thus, we explored the dose-dependent motivational responses induced by opiorphin using the forced swim test, the standard rat model of depression. In addition, to further understand the endogenous events triggered by opiorphin, we investigated the specific involvement of mu- or delta-opioid receptor-dependent pathways. In parallel, the locomotor activity test was used to detect possible sedation or hyperactivity. Here, we report for the first time that at 1-2 mg/kg i.v. doses, opiorphin elicited antidepressant-like effects by activating endogenous delta-opioidergic pathways, since that activation was reversed by the selective delta-opioid antagonist naldrindole (10 mg/kg i.p.). The antidepressive behavioral responses exerted by opiorphin are specific at systemically active doses. Treated-rats did not develop either hypo- or hyper-active responses in a locomotor test or amnesic behavioral response in the passive avoidance rat model. In addition, opiorphin did not induce either anxiolytic-, or anxiogenic-like responses in the conditioned defensive burying test. Taking the data together, we conclude that opiorphin is able to elicit antidepressant-like effects, mediated via delta-opioid receptor-dependent pathways, by modulating the concentrations of endogenous enkephalin released in response to specific physical and/or psychological stimuli. Thus, opiorphin or optimized derivatives is a promising single candidate to treat disorders that include both pain and mood disorders, particularly depression.

L’article Human opiorphin is a naturally occurring antidepressant acting selectively on enkephalin-dependent delta-opioid pathways est apparu en premier sur ETAP-LAB.

Lesions to the ventral, but not the dorsal, medial prefrontal cortex enhance latent inhibition.

Gregory — Mon, 24 May 2010 13:00:54 +0000

The acquisition of a conditioned response to a stimulus when it is paired with a reinforcer is retarded if the stimulus has previously been repeatedly pre-exposed in the absence of the reinforcer. This effect, called latent inhibition, has previously been found to be insensitive to lesions of the medial prefrontal cortex (mPFC) in rats. Using an on-baseline conditioned emotional response procedure, which is especially sensitive to small variations in the absolute magnitude of latent inhibition, we found increased latent inhibition following excitotoxic lesions of the mPFC (Experiment 1) or the ventral mPFC alone (Experiment 2) as compared with sham-operated control rats. Lesions restricted to the dorsal mPFC, however, were without effect (Experiment 2). These results are consistent with those of experiments employing another type of interference procedure, extinction. Together, these findings suggest that when different contingencies between a stimulus and a reinforcer are established in separate learning phases, lesions to the ventral mPFC result in increased interference between first-learned and second-learned contingencies. As a consequence, retrieval of the second-learned contingency is impaired, and performance is dominated by the first-learned contingency. These findings are discussed in light of the use of latent inhibition to model cognitive deficits in schizophrenia.

L’article Lesions to the ventral, but not the dorsal, medial prefrontal cortex enhance latent inhibition. est apparu en premier sur ETAP-LAB.

Diuretic and antioxidant effects of Cacti-Nea, a dehydrated water extract from prickly pear fruit, in rats

Gregory — Thu, 01 Apr 2010 19:12:16 +0000

Dehydrated extract of the prickly pear fruit Opuntia ficus indica, Cacti-Nea, was evaluated for its chronic diuretic and antioxidant effects in Wistar rats. Cacti-Nea was orally administered daily for seven days at the dose of 240 mg/kg/day. A positive group was orally treated with hydrochlorothiazide at the dose of 10 mg/kg/day and a control group with vehicle. Daily measurements of body weight, urine volume, and concentration of sodium, potassium and uric acid in urine were performed for each rat. At the end of the study, the blood globular level of glutathione peroxidase was determined. Cacti-Nea significantly increased the urine volumes excreted by rats in comparison with the control group and it showed a trend to reduce significantly the body weight gain of rats. No significant differences were observed in the urine concentration of sodium, potassium and uric acid in comparison with the control group. The chronic diuretic effects of Cacti-Nea were comparable with that of the standard drug hydrochlorothiazide. Chronic oral administration of Cacti-Nea significantly increased the blood globular levels of glutathione peroxidase in comparison with control and hydrochlorothiazide groups. The prickly pear fruit extract Cacti-Nea demonstrated chronic diuretic and antioxidant effects in Wistar rats with respect to the excretion of the metabolites.

L’article Diuretic and antioxidant effects of Cacti-Nea, a dehydrated water extract from prickly pear fruit, in rats est apparu en premier sur ETAP-LAB.

Preventive effects of different probiotic formulations on travelers’ diarrhea model in wistar rats : preventive effects of probiotics on TD

Gregory — Thu, 01 Apr 2010 19:11:31 +0000

A new animal model of travelers’ diarrhea has been developed by infecting rats orally with a strain of enterotoxigenic Escherichia coli in order to assess the efficacy of three probiotic formulations for the prevention of travelers’ diarrhea. Five groups of six rats were given daily (by oral gavage) either a placebo (negative and positive control groups), the suspension of bacterial probiotics called FF1, the yeast probiotic Saccharomyces boulardii, or a combination of both, called Protecflor(TM). After 14 days of treatment, all groups except the negative control one were infected by oral administration of E. coli. Body temperature, body weight, food and water consumption, stools consistency, behavior, and cytokines secretion were disturbed following E. coli infection. Probiotics-treated groups generally displayed less-pronounced symptoms, the combination of probiotics Protecflor(TM) being the most effective.

L’article Preventive effects of different probiotic formulations on travelers’ diarrhea model in wistar rats : preventive effects of probiotics on TD est apparu en premier sur ETAP-LAB.

Antidepressant-like properties of cocoa’s polyphenols The role of flavanoids and flavanols on depression

Gregory — Mon, 21 Dec 2009 13:01:07 +0000

In the last ten years, cocoa and bitter chocolate with a high content of cocoa have received much attention due to their significant polyphenol contents, and thus, have been recognized as significant sources of phytochemicals with healthful effects. Increasing evidence from experimental preclinical and clinical studies using cocoa polyphenols extracts or dark chocolate suggest an important role for these high-flavanol-containing products in various human pathologies. In fact, cocoa’s polyphenols are susceptible to induce stimulant, relaxant, euphoriant, tonic and antidepressant effects. This article reviews the various cocoa’s flavanols, aiming to establish their implications on mood state, particularly on depression, a major public health problem affecting about 12 percent of the world population.

Link to the article

L’article Antidepressant-like properties of cocoa’s polyphenols The role of flavanoids and flavanols on depression est apparu en premier sur ETAP-LAB.

Report of a glycemic imbalance in a diabetic patient after initiation of nicotine replacement therapy

Gregory — Tue, 24 Nov 2009 13:01:26 +0000

In the present study, we report the case of a patient with diabetes mellitus whose glycemic control was disrupted during hospitalization after a nicotine replacement therapy. Dosage adjustments along with a long-acting insulin treatment were used in order to obtain a new glycemic control. A possible explanation is that this metabolic disturbance was provoked by an overestimation of the patient’s actual nicotine consumption at the onset of the nicotine withdrawal program.

Link to the article

L’article Report of a glycemic imbalance in a diabetic patient after initiation of nicotine replacement therapy est apparu en premier sur ETAP-LAB.

Variations in illumination, closed wall transparency and/or extramaze space influence both baseline anxiety and response to diazepam in the rat elevated plus-maze

Gregory — Thu, 01 Oct 2009 19:10:52 +0000

Numerous methodological-related variables have been demonstrated to influence the baseline anxiety level of rodents exposed to the elevated plus-maze (EPM), raising questions about the sensitivity of this test for the detection of the effects of anxiolytic drugs. Thus, the present study was designed (1) to assess the combined effects of illumination (40-lx red or white light), closed wall type (walls made of translucent or opaque material) and extramaze space size (small or spacious experimental room) on rat behaviour, and (2) to investigate the effects of such parameters on the relevance of the maze for detecting the effects of diazepam orally administrated at the anxiolytic dose of 3 mg/kg. Results indicate that illumination and closed wall type are two main independent parameters that are able to modify the open arm avoidance. Moreover, the closed wall type interacts with the extramaze space size since the reduction of the open arm exploration induced by opaque closed walls is two-fold stronger in the spacious experimental room than in the small one. Finally, the diazepam anxiolytic activity is significantly detected in our laboratory in specific EPM conditions (maze with opaque walls, use of a red light, maze located in a spacious experimental room). In conclusion, the present study demonstrates that an inappropriate baseline anxiety level due to the methodological use of the EPM can dramatically reduce the sensitivity of the maze for the detection of benzodiazepine-related compounds. This study also provides new insights into the perception of the EPM open space in rats.

L’article Variations in illumination, closed wall transparency and/or extramaze space influence both baseline anxiety and response to diazepam in the rat elevated plus-maze est apparu en premier sur ETAP-LAB.

Hippocampal-dependent spatial memory functions might be lateralized in rats: an approach combining gene expression proﬁling and reversible inactivation

Gregory — Tue, 01 Sep 2009 19:15:43 +0000

The hippocampus is involved in spatial memory processes, as established in a variety of species such as birds and mammals including humans. In humans, some hippocampal-dependent memory functions may be lateralized, the right hippocampus being predominantly involved in spatial navigation. In rodents, the question of possible lateralization remains open. Therefore, we first microdissected the CA1 subregion of the left and right dorsal hippocampi for analysis of mRNA expression using microarrays in rats having learnt a reference memory task in the Morris water-maze. Relative to untrained controls, 623 genes were differentially expressed in the right hippocampus, against only 74 in the left hippocampus, in the rats that had learnt the hidden platform location. Thus, in the right hippocampus, 299 genes were induced, 324 were repressed, and about half of them participate in signaling and transport, metabolism, and nervous system functions. In addition, most differentially expressed genes associated with spatial learning have been previously related to synaptic plasticity and memory. We then subjected rats to unilateral (left or right) or bilateral reversible functional inactivations in the dorsal hippocampus; lidocaine was infused either before each acquisition session or before retrieval of a reference spatial memory in the Morris water maze. We found that after drug-free acquisition, right or bilateral lidocaine inactivation (vs. left, or bilateral phosphate buffered saline (PBS) infusions) of the dorsal hippocampus just before a delayed (24 h) probe trial impaired performance. Conversely, left or bilateral hippocampus inactivation (vs. right, or bilateral PBS infusions) before each acquisition session weakened performance during a delayed, drug-free probe trial. Our data confirm a functional association between transcriptional activity within the dorsal hippocampus and spatial memory in the rat. Further, they suggest that there could be a leftward bias of hippocampal functions in engram formation or information transfer, and a rightward bias in spatial memory storage/retrieval processes.

L’article Hippocampal-dependent spatial memory functions might be lateralized in rats: an approach combining gene expression proﬁling and reversible inactivation est apparu en premier sur ETAP-LAB.

Effects of a Bovine Alpha S1-Casein Tryptic Hydrolysate (CTH) on Sleep Disorder in Japanese General Population

Gregory — Fri, 21 Aug 2009 19:14:53 +0000

This study describes the effect of bovine alpha-S1 casein tryptic hydrolysate (CTH) in a representative sample of day-time workers from the general population of Japan with the occurrence of insomnia during the preceding six months. To investigate this issue, 32 subjects, aged between 25 and 40 years, were examined for the subjective sleep quality using the Japanese Pittsburg Sleep Quality Index (PSQI-J). CTH significantly improves the PSQI total score of the treated subjects. It particularly improves the sleep quality after two weeks of treatment, decreases the sleep latency and the daytime dysfunction after four weeks of treatment. Given the antistress properties of CTH, it seems possible to relate the detected improvement of sleep aspects to a reduction of stress following its’ chronic administration. In conclusion, being given its beneficial effects and its absence of negative side effects, it would be advantageous to use the CTH to improve chronic insomnia in the Japanese general population. However, further studies will be necessary in order to clarify the essential aspect of CTH properties in the sleep problems.

Link to the article

L’article Effects of a Bovine Alpha S1-Casein Tryptic Hydrolysate (CTH) on Sleep Disorder in Japanese General Population est apparu en premier sur ETAP-LAB.

Anxiolytic-like effects and safety profile of a tryptic hydrolysate from bovine alpha s1-casein in rats

Gregory — Mon, 01 Jun 2009 19:14:07 +0000

The anxiolytic activity and adverse benzodiazepine-like effects of a bovine alpha s1-casein tryptic hydrolysate (CH) were evaluated. The effects of CH orally administered at doses of 5 and 15 mg/kg were compared with those of diazepam (DZ) at 3 mg/kg in the conditioned defensive burying test. Rats treated either with CH at 15 mg/kg or with DZ showed a decrease in anxiety. A drug-related difference was observed in terms of duration, as the anxiolytic-like action of CH was maintained after 7 days with twice-daily administration, whereas that of DZ was not. CH and DZ were then evaluated for their potential effects on memory in a passive avoidance paradigm. CH-treated rats had significantly longer latencies before entering the dark compartment where they were previously delivered a shock, indicating better retention relative to DZ-treated rats. In the final test, CH and DZ were evaluated for place preference, an index of the possible addictive potential of these substances. DZ-treated rats spent more time in the compartment associated with drug exposure than control rats. This effect was not found in CH-treated rats. Thus, CH did not display side effects associated with DZ, despite its affinity for gamma-aminobutyric acid(A) (GABA(A)) receptors. Specific linking of CH on GABA(A) receptor function involved in anxiolysis, but not on that implied in memory-impairing effects, may be hypothesized to explain its specific activity. This profile might render it advantageous for nutritional purposes.

L’article Anxiolytic-like effects and safety profile of a tryptic hydrolysate from bovine alpha s1-casein in rats est apparu en premier sur ETAP-LAB.

An oligofructose-enriched inulin diet: cognitive and physical performances in rats

Gregory — Fri, 01 May 2009 19:13:39 +0000

The aim of the present study was to investigate the effects of long-term intervention with oligofructose-enriched inulin on behavioral cognitive, and visuomotor coordination in rats. Three-month-old male and female rats were randomly distributed into two groups receiving either a diet with 10% oligofructose-enriched inulin (SYN1) or a standard diet tested at 12, 18 and 24 months of age. Rats supplemented with SYN1 showed age- and sex-related improvements in spatial learning abilities, depression, anxiety, and visuomotor speed more prominent at 12 and 18 months. These results suggest that long-term intervention with SYN1 can improve cognitive and emotional aspects of aging.

Link to the article

L’article An oligofructose-enriched inulin diet: cognitive and physical performances in rats est apparu en premier sur ETAP-LAB.

Two acute psychotic episodes after administration of bupropion: a case of involuntary rechallenge

Gregory — Wed, 01 Apr 2009 19:18:16 +0000

Bupropion is an antidepressant drug also used as a smoking cessation aid, which inhibits norepinephrine and dopamine re-uptake. Given its pharmacological properties, it has been associated with reports on psychosis and acute delirious episodes. Case We report the case of a patient with schizoaffective disorder who developed two psychotic episodes respectively after a four and a two-day administration of sustained-release (SR) bupropion at a dose of 150 mg/day. To our knowledge, this is the first reported case of involuntary rechallenge with bupropion SR during a smoking cessation program. Conclusion There is a serious risk of incorrectly identifying bupropion as only a therapy for nicotine withdrawal without taking the precaution of exploring possible psychiatric co-morbidity with addiction. Our case illustrates the problem.

L’article Two acute psychotic episodes after administration of bupropion: a case of involuntary rechallenge est apparu en premier sur ETAP-LAB.

Food dextrin protects against colonic inflamamtion and prevents cognitive impairments

Gregory — Thu, 01 Jan 2009 19:17:42 +0000

The aim of the present study was to investigate the protective effects of the dextrin NUTRIOSE® 6 (Dex) on colonic inflammation. Five percent of Dex or Glucose (Glu) diets were administered for 2 weeks to Wistar male rats prior to colitis induction with 1mg of TNBS (2,4,6-Trinitrobenzenesulfonic acid) or 20% ethanol (vehicle). An aversive light stimulus avoidance test (ALSAT) was performed to assess the cognitive performances of rats that are correlated to pain. Growth, food intake and biological parameters as caecal wall thickness, enzyme activities, short chain fatty acid content were investigated. Macro and microscopic scores of colonic inflammation of each treatment groups were compared. The results suggest that Dex prevents colonic inflammation induced by ethanol and TNBS administrations and have positive consequences on cognitive impairments.

Link to the article

L’article Food dextrin protects against colonic inflamamtion and prevents cognitive impairments est apparu en premier sur ETAP-LAB.

Effect of music therapy on anxiety and depression in patients with Alzheimer’s type dementia: randomised, controlled study

Gregory — Thu, 01 Jan 2009 19:16:54 +0000

BACKGROUND/AIMS:

Numerous studies have indicated the value of music therapy in the management of patients with Alzheimer’s disease. A recent pilot study demonstrated the feasibility and usefulness of a new music therapy technique. The aim of this controlled, randomised study was to assess the effects of this new music therapy technique on anxiety and depression in patients with mild to moderate Alzheimer-type dementia.

METHODS:

This was a single-centre, comparative, controlled, randomised study, with blinded assessment of its results. The duration of follow-up was 24 weeks. The treated group (n = 15) participated in weekly sessions of individual, receptive music therapy. The musical style of the session was chosen by the patient. The validated ‘U’ technique was employed. The control group (n = 15) participated under the same conditions in reading sessions. The principal endpoint, measured at weeks 1, 4, 8, 16 and 24, was the level of anxiety (Hamilton Scale). Changes in the depression score (Geriatric Depression Scale) were also analyzed as a secondary endpoint.

RESULTS:

Significant improvements in anxiety (p < 0.01) and depression (p < 0.01) were observed in the music therapy group as from week 4 and until week 16. The effect of music therapy was sustained for up to 8 weeks after the discontinuation of sessions between weeks 16 and 24 (p < 0.01).

CONCLUSION:

These results confirm the valuable effect of music therapy on anxiety and depression in patients with mild to moderate Alzheimer’s disease. This new music therapy technique is simple to implement and can easily be integrated in a multidisciplinary programme for the management of Alzheimer’s disease.

L’article Effect of music therapy on anxiety and depression in patients with Alzheimer’s type dementia: randomised, controlled study est apparu en premier sur ETAP-LAB.

Synthesis and rheological properties of hydrogels based on amphiphilic alginate-amide derivatives

Gregory — Thu, 01 Jan 2009 19:16:18 +0000

New amphiphilic derivatives of sodium alginate were prepared by covalent attachment of dodecylamine onto the polysaccharide via amide linkages at different substitution ratios, using 2-chloro-1-methylpyridinium iodide (CMPI) as coupling reagent. The aim was to limit the progressive loss of associative behaviour which occurs in the case of previously described dodecyl ester alginate derivatives due to hydrolysis of ester bonds. A series of hydrogels was obtained which differed by the amount of attached dodecyl tails. The stability and viscoelastic properties were evaluated and compared to those of hydrogels obtained with alginate esters. The observed differences were discussed in relation to the synthesis procedures. The advantages of amide links are underlined, especially with regard to long-term stability of hydrogels.

L’article Synthesis and rheological properties of hydrogels based on amphiphilic alginate-amide derivatives est apparu en premier sur ETAP-LAB.

Antidepressant-like effects of a cocoa polyphenolic extract in Wistar-Unilever rats

Gregory — Mon, 01 Dec 2008 19:20:59 +0000

Depression is a major public health problem affecting about 12% of the world population. Drugs exist but they have many side effects. In the last few years, natural substances (e.g. flavonoids) have been tested to cure such disorders. Cocoa polyphenolic extract is a complex compound prepared from non-roasted cocoa beans containing high levels of flavonoids. The antidepressant-like effect of cocoa polyphenolic extract was evaluated using the forced swimming test in rats. Cocoa polyphenolic extract significantly reduced the duration of immobility at both doses of 24 mg/kg/14 days and 48 mg/kg/14 days, although no change of motor dysfunction was observed with the two doses tested in the open field. The results of the forced swimming test after a subchronic treatment and after an additional locomotor activity test confirm the assumption that the antidepressant-like effect of cocoa polyphenolic extract in the forced swimming test model is specific. Further, it can be speculated that this effect might be related to its content of active polyphenols.

L’article Antidepressant-like effects of a cocoa polyphenolic extract in Wistar-Unilever rats est apparu en premier sur ETAP-LAB.

Effects of lifelong intervention with an oligofructose-enriched inulin in rats on general health and lifespan

Gregory — Mon, 01 Dec 2008 19:20:19 +0000

Ageing is associated with changes in physiology and morphology; nutritional strategies to decrease morbidity and to prolong life are of high interest. The aim of the study was to investigate the effects of lifelong supplementation with an oligofructose-enriched inulin on morphological and biological markers and lifespan in male and female rats. Male and female rats, age 3 months, were randomised into two groups to receive either a diet with 10 % of an oligofructose-enriched inulin (Synergy 1) or a standard diet (control) for 27 months. The rats were weighed every 2 weeks and their food intake was evaluated on four successive days every 4-6 weeks. Samples were taken at 12, 18 and 24 months of age. During the whole intervention period, male rats receiving Synergy 1 (SYN1-M) displayed lower body weight, cholesterol and plasma triacylglycerolaemia compared with the controls (Cont-M). The survival rate at 24 months of age of SYN1-M rats was 35.3 % greater than that of Cont-M rats. In female rats, the Synergy 1 supplementation (SYN1-F) group also reduced body weight, cholesterol and triacylglycerolaemia levels, but results were less consistent over the experiment. The survival rate at 24 months of age in SYN1-F rats was 33.3 % greater compared with that of the control (Cont-F) group. To conclude, lifelong intervention with Synergy 1 improved biological markers during ageing and survival rate (lifespan) of rats.

L’article Effects of lifelong intervention with an oligofructose-enriched inulin in rats on general health and lifespan est apparu en premier sur ETAP-LAB.

Impact of sugar replacers on cognitive performance and function in rats

Gregory — Sat, 01 Nov 2008 19:19:35 +0000

Glycaemic responses to the dextrin NUTRIOSE 6 (Dex) and the MALTISORB maltitol (Mal) have been studied previously but their effects on vigilance and cognitive performances are still not known. The present study assesses dose-related glycaemic responses following Dex administration and the hypothesis that Dex and Mal could modulate the glycaemic response, improve vigilance under stress conditions and improve cognitive performances in rats. The glycaemic responses following Dex and corn syrup GLUCIDEX IT 21 (CoS) solutions at 0.3, 0.5 and 1.0 g/kg body weight administered by oral administration (experiment 1) and glycaemic responses to three cereal bars (standard (CoS), Dex or Dex/Mal bar) (experiment 2) were evaluated. Rats having eaten cereal bars were submitted to vigilance and aversive light stimulus avoidance conditioning tests to assess their vigilance and cognitive performances. The first experiment showed that the glycaemic response to both products is dose-related and that CoS induced a glycaemic response three times higher than the Dex response. The second experiment showed the same glycaemic response for the three cereal bar-treated rats. Yet, an increase in the vigilance of Dex/Mal-treated rats as well as a better discrimination between two levers in the cognitive test for Dex- and Dex/Mal-treated rats were noticed. These results suggest that the glycaemic response is not the only factor to be considered in predicting the efficiency of a food ingredient on vigilance and cognitive performances: these behaviours are improved after Dex- and Mal-prepared cereal bar ingestion whereas the glycaemic response does not differ from the CoS-prepared bar.

L’article Impact of sugar replacers on cognitive performance and function in rats est apparu en premier sur ETAP-LAB.

Effects of long-term administration of a cocoa polyphenolic extract (Acticoa powder) on cognitive performances in aged rats

Gregory — Tue, 01 Jul 2008 19:19:02 +0000

Numerous studies have indicated that increased vulnerability to oxidative stress may be the main factor involved in functional declines during normal and pathological ageing, and that antioxidant agents, such as polyphenols, may improve or prevent these deficits. We examined whether 1-year administration of a cocoa polyphenolic extract (Acticoa powder), orally delivered at the dose of 24 mg/kg per d between 15 and 27 months of age, affects the onset of age-related cognitive deficits, urinary free dopamine levels and lifespan in old Wistar-Unilever rats. Acticoa powder improved cognitive performances in light extinction and water maze paradigms, increased lifespan and preserved high urinary free dopamine levels. These results suggest that Acticoa powder may be beneficial in retarding age-related brain impairments, including cognitive deficits in normal ageing and perhaps neurodegenerative diseases. Further studies are required to elucidate the mechanisms of cocoa polyphenols in neuroprotection and to explore their effects in man.

L’article Effects of long-term administration of a cocoa polyphenolic extract (Acticoa powder) on cognitive performances in aged rats est apparu en premier sur ETAP-LAB.

Anti-inflammatory senescence actives 5203-L molecule to promote healthy aging and prolongation of lifespan

Gregory — Tue, 01 Apr 2008 19:23:35 +0000

The aging process depends on genetic stability, metabolic control, and resistance to stress; longevity in particular seems related to resistance to stress. Responses to stress anticipate adaptation to an unacceptable disparity between real or imagined personal experience and expectation, including adaptive stress, anxiety, and depression. However, if stress persists, it may lead to chronic diseases, ranging from inflammation and cancer to degenerative diseases. For some time, only remarkable stress was acknowledged to induce immune and vascular alterations, such as infection or hypertension. Now it is known that moderate stress independent of conventional risk factors can induce a potent alteration of health conditions and consequently shorten life quality and lifespan. Inflammation is a critical defense mechanism, that, uncontrolled, contributes to chronic conditions with inflammatory pathogenesis. Stressful life conditions turn out to induce a diffuse (systemic) pro-inflammatory status. Subclinical chronic inflammation is an important pathogenic factor in the development of metabolic syndrome, a cluster of common pathologies, including cardiovascular disease. Markers include mediators associated with endothelial activation and dysfunction. This work reports the in vitro and in vivo effects of the monoterpene AISA 5203-L on human vascular endothelial cells in reversing replicative senescence in preventing and alleviating nonpathological stress, as assessed by a functional observational battery (FOB) of 44 tests, addressing behavioral, neurological, and physiological criteria.

L’article Anti-inflammatory senescence actives 5203-L molecule to promote healthy aging and prolongation of lifespan est apparu en premier sur ETAP-LAB.

Protective effect of Acticoa powder, a cocoa polyphenolic extract, on prostate carcinogenesis in Wistar-Unilever rats

Gregory — Fri, 01 Feb 2008 19:22:48 +0000

The effects of Acticoa powder on prostate carcinogenesis were investigated using the N-methylnitrosourea and testosterone propionate prostate tumor model. Sixty male Wistar-Unilever rats were randomly divided in four groups of 15 rats: one control group not induced but treated with vehicle (not induced+vehicle) and three chemo-induced groups. Two weeks before prostate tumor induction and then throughout the experiment, chemo-induced rats were orally treated with Acticoa powder at 24 (chemo-induced+Acticoa powder24) or 48 (chemo-induced+Acticoa powder48) mg/kg or with vehicle (chemo-induced+vehicle), daily from Monday to Friday. Survival, body weight, food and water consumption were recorded throughout the experiment. Six rats per group were randomly killed 9 months after the prostate tumor induction for histopathological analysis of prostates. A reduction in the incidence of prostate tumors was observed for the chemo-induced+Acticoa powder48-treated group in comparison with the chemo-induced+vehicle-treated group and no tumors were observed in the chemo-induced+Acticoa powder24-treated group as in the not induced+vehicle-treated group after 9 months. The nine remaining rats per group were maintained in a long-term survival study. The life span of the chemo-induced+Acticoa powder24-treated group was significantly increased in comparison with the chemo-induced+Acticoa powder48 and the chemo-induced+vehicle-treated groups, close to the one of the not induced+vehicle-treated group. A significant reduction in the incidence of prostate tumors was also observed for the chemo-induced+Acticoa powder24 and chemo-induced+Acticoa powder48-treated groups in comparison with the chemo-induced+vehicle-treated group. In conclusion, Acticoa powder at 24 mg/kg protected rats from prostate carcinogenesis when chronically given before the initiation and promotion phases of induction.

L’article Protective effect of Acticoa powder, a cocoa polyphenolic extract, on prostate carcinogenesis in Wistar-Unilever rats est apparu en premier sur ETAP-LAB.

Anxiolitic and antidepressant-like effects of Garum armoricum® (GA), a blue ling finsh protein autolysate in male wistar rats

Gregory — Tue, 01 Jan 2008 19:22:18 +0000

The anxiolytic- and antidepressant-like effects of Garum Armoricum® (GA), a protein autolysate from the blue ling fish, were studied in male Wistar rats using the conditioned defensive burying (CDB) and the forced swimming (FST) tests, respectively. In the CDB, all doses of GA (25, 50 and 100 mg/kg, PO) decreased the global score of anxiety and the latency of the first approach towards the probe after shock, in a similar way to diazepam (DZP) at the dose of 3 mg/kg, PO. But unlike DZP, the latency before touching again the probe after shock was not significantly reduced by GA. In the FST, the two higher doses of GA (15 and 45 mg/kg, PO) reduced immobility time in a similar way to imipramine (IMI) at the dose of 20 mg/kg, PO. But unlike IMI, GA did not reduce open-field activity and, unlike DZP, did not cause a place preference to develop. These results indicate the potential anxiolytic- and antidepressant-like properties of GA in the absence of any change in cerebral activation and dependence. These psychotropic properties of GA may be due to the synergistic action of its active constituents.

Link to the article

L’article Anxiolitic and antidepressant-like effects of Garum armoricum® (GA), a blue ling finsh protein autolysate in male wistar rats est apparu en premier sur ETAP-LAB.

The effects of Garum armoricum® (GA) on elevated-plus maze and conditioned light extinction tests in rats

Gregory — Tue, 01 Jan 2008 19:21:48 +0000

Garum Armoricum® (GA), a compound rich in polyunsaturated fatty acids, free amino acids, small peptides, vitamins and minerals, was evaluated on two fear-related assays in rats. GA and diazepam (DZP) increased entries into open arms relative to placebo, as well as percentage of open arm entries in the elevated plus-maze test. In a similar fashion, all drugged groups spent more time inside the open arms and less time inside the enclosed arms. After a two-day period of conditioned avoidance learning of an aversive bright light, GA and vehicle groups successfully discriminated the active from the inactive lever. On the initial day of acquisition, GA and piracetam (PIR) groups achieved successful discrimination though the control group did not. These results indicate that GA may have anxiolytic-like effects without causing learning deficiencies. These psychotropic properties of GA may be due to the synergistic action of its active constituents.

Link to the article

L’article The effects of Garum armoricum® (GA) on elevated-plus maze and conditioned light extinction tests in rats est apparu en premier sur ETAP-LAB.

Therapeutic effect of ACTICOA powder, a cocoa polyphenolic extract, on experimentally induced prostate hyperplasia in Wistar-Unilever rats

Gregory — Sat, 01 Dec 2007 19:26:16 +0000

Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate that results in obstructive lower urinary tract symptoms. Plant extracts are frequently used to treat BPH rather than therapeutics that can cause severe side effects. ACTICOA() (Ba0rry Callebaut France, Louviers, France) powder (AP) is a cocoa polyphenolic extract, and we have shown in a previous study that oral treatment with AP prevented prostate hyperplasia. This study investigated whether AP could improve established prostate hyperplasia using the same testosterone propionate (TP)-induced prostate hyperplasia model in rats. Male Wistar-Unilever rats were randomly divided in four groups of 12 rats: one group injected with corn oil and orally treated with the vehicle (negative control) and three groups injected subcutaneously with TP and orally treated with the vehicle (positive control) or AP at 24 (AP24) and 48 (AP48) mg/kg/day. Treatments started 1 week after the start of the induction of prostate hyperplasia and lasted for 2 weeks. The influence of TP and AP on body weights, food and water consumptions, plasma polyphenolic concentration, and serum dihydrotestoterone (DHT) level of rats was examined. At completion of the study, rats were sacrificed, and the prostates were removed, cleaned, and weighed. The prostate size ratio (prostate weight/rat body weight) was then calculated. TP significantly influenced the body weight gain of the rats and their food and water consumptions, while AP reduced significantly these differences in a dose-dependent manner. AP significantly reduced serum DHT level and prostate size ratio in comparison with positive controls also dose-dependently. In conclusion, AP orally administered was effective for reducing established prostate hyperplasia, especially at the dose of 48 mg/kg/day.

L’article Therapeutic effect of ACTICOA powder, a cocoa polyphenolic extract, on experimentally induced prostate hyperplasia in Wistar-Unilever rats est apparu en premier sur ETAP-LAB.

Preventive effects of ACTICOA powder, a cocoa polyphenolic extract, on experimentally induced prostate hyperplasia in Wistar-Unilever rats

Gregory — Sat, 01 Dec 2007 19:25:33 +0000

Plant extracts are useful in the management of benign prostatic hyperplasia (BPH). This study investigates whether ACTICOA (Barry Callebaut France, Louviers, France) powder (AP), a cocoa polyphenolic extract, could prevent prostate hyperplasia induced by testosterone propionate (TP) in rats. Male Wistar-Unilever rats were randomly divided in four groups of 12 rats: one negative control group receiving subcutaneous injections of corn oil and treated with vehicle and three groups injected subcutaneously with TP and treated with the vehicle (positive control) or AP at 24 (AP24) and 48 (AP48) mg/kg/day. Treatments were given orally and started 2 weeks before the induction of prostate hyperplasia. The influence of TP and AP on body weights and food and water consumption of rats was examined. On day 36, rats were sacrificed, and the prostates were removed, cleaned, and weighed. The prostate size ratio (prostate weight/rat body weight) was then calculated. TP significantly influenced the body weight gain of the rats and their food and water consumption, while AP at both doses tested reduced significantly these differences. TP significantly increased prostate size ratio (P < .001), and this induced increase was significantly inhibited in AP-treated rats in comparison with positive controls (P < .001) in a dose-dependent manner. We conclude that AP can prevent TP-induced prostate hyperplasia and therefore may be beneficial in the management of BPH.

L’article Preventive effects of ACTICOA powder, a cocoa polyphenolic extract, on experimentally induced prostate hyperplasia in Wistar-Unilever rats est apparu en premier sur ETAP-LAB.

Preventive antioxidant effects of cocoa polyphenolic extract on free radical production and cognitive performances after heat exposure in Wistar rats.

Gregory — Mon, 28 May 2007 13:26:55 +0000

The preventive effects of ACTICOA powder (AP), a cocoa polyphenolic extract, on free radicals produced by leucocytes in rats after heat exposure (HE) and its protective effects on subsequent cognitive impairments were assessed. AP or vitamin E, the antioxidant reference, was orally administered to rats for 14 d before HE at 40 degrees C temperature during 2 h. The day after HE, free radical production by leucocytes in rats treated with AP or vitamin E was significantly reduced as compared to control. Unlike controls, AP- and vitamin E-treated rats discriminated between active lever and inactive levers in a light extinction paradigm. In the Morris water maze, escape latencies before reaching the hidden platform by AP- and vitamin E-treated rats decreased throughout testing. The daily oral administration of AP or vitamin E protected rats from cognitive impairments after HE by counteracting the overproduction of free radicals.

L’article Preventive antioxidant effects of cocoa polyphenolic extract on free radical production and cognitive performances after heat exposure in Wistar rats. est apparu en premier sur ETAP-LAB.

Structural and functional recovery elicited by combined putrescine and aminoguanidine treatment after aspirative lesion of the ﬁmbria–fornix and overlying cortex in the adult Rat

Gregory — Sun, 01 Apr 2007 19:24:43 +0000

Damage to the adult CNS often causes permanent deficits. Based on a lesion model of septohippocampal pathway aspiration in the rat, we attempted to promote neuronal cell survival and post-traumatic recovery by using a pharmacological treatment combining aminoguanidine and putrescine (AGP). The functional recovery was followed over 15 weeks before morphological analysis. AGP treatment produced a persistent attenuation (approximately 50%) of the lesion-induced hyperactivity, a reduction (approximately 60%) in the sensorimotor impairments and an improved performance in the water-maze task which did not, however, rely upon improved memory capabilities. AGP weakened the lesion-induced decrease in ChAT-positive neurons in the medial septum and the extent of thalamic retrograde necrosis (by approximately 30% in each case) and resulted in a partial cholinergic reinnervation of the dentate gyrus. These promising results support the idea that coadministration of putrescine and aminoguanidine might become a potent way to foster structural and functional recovery (or compensation) in the adult mammalian CNS after injury.

L’article Structural and functional recovery elicited by combined putrescine and aminoguanidine treatment after aspirative lesion of the ﬁmbria–fornix and overlying cortex in the adult Rat est apparu en premier sur ETAP-LAB.

Human Opiorphin, a natural antinociceptive modulator of opioid-dependent pathways

Gregory — Wed, 01 Nov 2006 19:24:09 +0000

Mammalian zinc ectopeptidases play important roles in turning off neural and hormonal peptide signals at the cell surface, notably those processing sensory information. We report here the discovery of a previously uncharacterized physiological inhibitor of enkephalin-inactivating zinc ectopeptidases in humans, which we have named Opiorphin. It is a QRFSR peptide that inhibits two enkephalin-catabolizing ectoenzymes, human neutral ecto-endopeptidase, hNEP (EC 3.4.24.11), and human ecto-aminopeptidase, hAP-N (EC 3.4.11.2). Opiorphin displays potent analgesic activity in chemical and mechanical pain models by activating endogenous opioid-dependent transmission. Its function is closely related to the rat sialorphin peptide, which is an inhibitor of pain perception and acts by potentiating endogenous μ- and δ-opioid receptor-dependent enkephalinergic pathways. Here we demonstrate the functional specificity in vivo of human Opiorphin. The pain-suppressive potency of Opiorphin is as effective as morphine in the behavioral rat model of acute mechanical pain, the pin-pain test. Thus, our discovery of Opiorphin is extremely exciting from a physiological point of view in the context of endogenous opioidergic pathways, notably in modulating mood-related states and pain sensation. Furthermore, because of its in vivo properties, Opiorphin may have therapeutic implications.

L’article Human Opiorphin, a natural antinociceptive modulator of opioid-dependent pathways est apparu en premier sur ETAP-LAB.

Reversible inactivation of the dorsal hippocampus by tetrodotoxin or lidocaine : a comparative study on cerebral functional activity and motor coordination in the Rat

Gregory — Fri, 01 Sep 2006 19:28:54 +0000

Reversible inactivation of the hippocampus by lidocaine or tetrodotoxin is used to investigate implications of this structure in memory processes. Crucial points related to such inactivation are the temporal and spatial extents of the blockade. We compared effects of intrahippocampal infusions of commonly-used doses of lidocaine (5 or 10 mug) or tetrodotoxin (5 or 10 ng) in rats at two post-infusion delays (5 or 30 min), using 2-deoxyglucose autoradiography to visualize local cerebral glucose metabolism, and beam-walking performance to assess motor coordination. In addition, memory retrieval was evaluated in a water maze after bilateral infusions of 10 mug lidocaine. A unilateral tetrodotoxin infusion induced dose- and time-dependent reductions of 2-deoxyglucose uptake in the vicinity of the infusion site (dorsal hippocampus: -29% to -67%) and in other ipsi- and contralateral brain regions (ventral hippocampus, lateral thalamus, cortical regions). The maximal effect was at 10 ng, at the delay of 30 min between the tetrodotoxin infusion and the 2-deoxyglucose injection. Uni- and bilateral infusions of tetrodotoxin induced dramatic motor coordination deficits. Conversely, lidocaine reduced 2-deoxyglucose uptake (-19%) in the dorsal hippocampus only at 10 mug, with weak extrahippocampal effects. Whether infused uni- or bilaterally and regardless of the dose, lidocaine did not alter motor coordination. When infused bilaterally, however, 10 microg of lidocaine impaired short-term retrieval of spatial information in a water maze. Because lidocaine i) induced a weak though significant functional blockade mainly restricted to the infusion site, ii) had no consequences on motor coordination and, nevertheless iii) altered short-term spatial memory retrieval, we conclude that acute intrahippocampal infusions of lidocaine may offer some advantages over tetrodotoxin at the doses used herein.

L’article Reversible inactivation of the dorsal hippocampus by tetrodotoxin or lidocaine : a comparative study on cerebral functional activity and motor coordination in the Rat est apparu en premier sur ETAP-LAB.

Ethological comparison of the effects of a bovine αs1-casein tryptic hydrolysate and diazepam on the behaviour of rats in two models of anxiety

Gregory — Sat, 01 Jul 2006 19:28:35 +0000

A bovine alpha s1-casein tryptic hydrolysate was previously demonstrated to display an anxiolytic-like activity in the conditioned defensive burying and in the elevated plus-maze models when i.p. injected. The present study assessed the anxiolytic-like effects of this tryptic hydrolysate after an oral administration in rats faced to the same behavioural situations using diazepam as a reference. In a first experiment, the behavioural effects of the hydrolysate in the conditioned defensive burying test were investigated at doses ranging 5-50 mg/kg. The results showed that the minimal dose required to elicit an anxiolytic-like activity is 15 mg/kg. In a second experiment, the alpha s1-casein tryptic hydrolysate (15 mg/kg, p.o.) was demonstrated to display an anxiolytic-like activity similar to diazepam (3 mg/kg, p.o.) in the conditioned defensive burying test and the elevated plus-maze. However, the ethological analysis of behaviour indicated that this hydrolysate has a different activity compared to diazepam. While diazepam induced a disinhibition state in rats, possibly related to the risk-taking behaviour observed after a benzodiazepine ingestion in humans, the tryptic hydrolysate did not display such a side effect. These results suggest that the mechanism of action of the bovine alpha s1-casein tryptic hydrolysate may differ from that of diazepam.

L’article Ethological comparison of the effects of a bovine αs1-casein tryptic hydrolysate and diazepam on the behaviour of rats in two models of anxiety est apparu en premier sur ETAP-LAB.

A tryptic hydrolysate from bovine milk alphaS1-casein improves sleep in rats subjected to chronic mild stress

Gregory — Thu, 01 Jun 2006 19:27:48 +0000

The putative effects of a tryptic bovine alphaS1-casein hydrolysate on stress-induced sleep disorders were investigated and their possible link with typical blood stress parameters such as plasma corticosterone concentrations and glycaemia was assessed. Rats were subjected to chronic stress in the form of environmental disturbances, while receiving an oral administration of the alphaS1-casein hydrolysate (CH). Chronic stress significantly reduced sleep duration in control rats during the first 2 days of the stress period, but stress-induced sleep disturbance was prevented in CH-treated rats. Indeed, CH administration allowed the maintenance of slow wave sleep (SWS) duration and even a slight increase in paradoxical sleep (PS) duration in treated rats. Results on plasma corticosterone concentrations and on glycemia values were inconclusive with respect to the implication of the HPA axis in this study. However, the protective effect of the alphaS1-casein hydrolysate on sleep during exposure to our chronic mild stress conditions may be mediated by modulation of the central adrenergic response.

L’article A tryptic hydrolysate from bovine milk alphaS1-casein improves sleep in rats subjected to chronic mild stress est apparu en premier sur ETAP-LAB.

Radially polarized ring and arc beams of a neodymium laser with an intra-cavity axicon.

Gregory — Wed, 24 May 2006 13:33:17 +0000

Placing a Brewster-angle axicon inside a laser resonator makes it possible to produce a radially-polarized (RP) oscillation pattern distributed on a thin ring or a portion of a ring. Laser-diode end-pumped, Nd:Y(3)Al(5)O(12) and Nd:YVO(4) lasers were studied. Spatially coherent RP beams distributed on circular arcs were obtained with a polarization contrast ratio up to 80:1. Incoherent RP outputs on a full ring were also produced with a polarization contrast ratio of about 5:1. Applications of these beams to increase absorption efficiency in laser-matter interaction are discussed.

L’article Radially polarized ring and arc beams of a neodymium laser with an intra-cavity axicon. est apparu en premier sur ETAP-LAB.

Behavioural and cognitive effects of oligofructose-enriched inulin in rats

Gregory — Fri, 01 Apr 2005 19:27:10 +0000

The behavioural and cognitive effects of oligofructose-enriched inulin at the doses of 5 and 10 % in the diet, orally ingested daily during 2 weeks, were investigated using a functional observational battery (FOB) and the light extinction test in male Wistar rats. Control rats received a standard diet and were tested in the same test situations. The behavioural effects were assessed 2 d before and 14 d after the beginning of the treatment period and the cognitive effects were investigated after the administration period by lever-pressing activity and learning discrimination using the light extinction test paradigm. In general, the study demonstrated that oligofructose-enriched inulin at 5 % in the diet, and particularly at 10 % in the diet, caused relaxing-like effects, stimulated and increased the general activity and interest of the rats to the test environment. In addition, both doses of oligofructose-enriched inulin showed significant effects on learning discrimination in male rats, in comparison with the control diet. These results suggest that oligofructose-enriched inulin, particularly at the dose of 10 %, improves cognitive performances in the light extinction test and the well-being of male rats using the FOB.

L’article Behavioural and cognitive effects of oligofructose-enriched inulin in rats est apparu en premier sur ETAP-LAB.

Effects of a tryptic hydrolysate from bovine milk alphaS1-casein on hemodynamic responses in healthy human volunteers facing successive mental and physical stress situations

Gregory — Tue, 01 Mar 2005 19:31:24 +0000

BACKGROUND:

Preclinical results in rats have demonstrated anxiolytic-like effects of a tryptic bovine alphaS1-casein hydrolysate.

AIM OF THE STUDY:

We investigated the putative effects of this tryptic hydrolysate on systolic (SBP), diastolic (DBP) blood pressures, heart rate (HR) values and plasma cortisol concentrations (CC) in human healthy volunteers facing successive stress situations.

METHODS:

The subjects were (double blind) randomly allocated to ingest three times, 12 hours apart, two capsules containing either 200 mg of alphaS1-casein hydrolysate (TS) or bovine skimmed milk powder as a placebo (CS). On the morning of the test day, a first blood sample for baseline measurement of CC was taken before the subjects were submitted to the Stroop test (ST) and, after a 30-min rest, to a Cold Pressor test (CPT). SBP, DBP, and HR were continuously recorded for 5 min before the ST and during each stress situation. A second blood sample was taken 15 min after the end of the CPT condition.

RESULTS:

ST and ST + CPT combined test situations increased SBP, DBP and HR. The significant “Treatment x SBP” and “Treatment x DBP” interactions indicated the lower percentage changes in SBP and DBP of the TS. In addition, the results showed a significant decrease of the CC in the TS but not in the CS throughout the ST + CPT combined stress tests. HR remained stable in TS between the initial rest period and the CPT unlike what happened in CS.

CONCLUSION:

On the basis of blood pressure and cortisol changes, these results suggest an antistress profile of this alphaS1-casein hydrolysate in human subjects.

L’article Effects of a tryptic hydrolysate from bovine milk alphaS1-casein on hemodynamic responses in healthy human volunteers facing successive mental and physical stress situations est apparu en premier sur ETAP-LAB.

The endogenous androgen-regulated sialorphin modulates male rat sexual behavior

Gregory — Wed, 01 Dec 2004 19:30:52 +0000

In sexually mature male rats, sialorphin is synthesized under androgenic control and its surge endocrine secretion is evoked in response to environmental acute stress. These findings led us to suggest that this signaling mediator might play a role in physiological and behavioral integration, especially reproduction. The present study investigates the effects induced by sialorphin on the male sexual behavior pattern. Intact male rats were treated in acute mode, with sialorphin at the 0.3, 1, and 3 microg/kg doses, before being paired with receptive female for 45 min. The data obtained show that sialorphin increased, in a dose-related manner, the occurrence of intromissions across the successive ejaculatory sequences. The rats treated with the highest 3 microg/kg dose significantly ejaculated less often compared to controls; however, 80% of them achieved up to three ejaculations. Further analyses of mount bouts for rats achieving three ejaculations reveal that there were significant stimulatory effects of sialorphin, at all doses, on the frequency of intromissions before ejaculation and on the propensity of males to engage in investigatory behavior directed to the female during the post-ejaculatory interval. Thus, sialorphin has the ability to modulate, at doses related to physiological circulating levels, the male rat mating pattern, that is, exerting a dual facilitative or inhibitory dose-dependent effect on the sexual performance, while stimulating the apparent sexual arousal or motivation. These findings led us to speculate that the endogenous androgen-regulated sialorphin helps modulate the adaptative balance between excitatory and inhibitory mechanisms serving appropriate male rat sexual response, depending on the context.

L’article The endogenous androgen-regulated sialorphin modulates male rat sexual behavior est apparu en premier sur ETAP-LAB.

Effects of different germination conditions on the contents of free protein and non-protein amino acids of commercial legumes

Gregory — Mon, 13 Sep 2004 13:37:51 +0000

Seeds of beans, lentils and peas were germinated for 2, 4 and 6 days, either under continuous light or continuous dark, and the free amino acids analysed by HPLC. The effects of germination on the free protein amino acids (FPA) and non-protein amino acids (FNPA) depended on the type of legumes and on the processing conditions. After germination of beans, histidine, glutamate, glycine, arginine, tyrosine and tryptophan contents decreased while, in lentils and peas, FPA increased after germination. Light germination gave the highest amounts of FPA in beans and lentils, but the lowest in peas. The FNPA changed markedly with germination. In beans, germination produced a reduction of α-amino adipic acid and an increase of GABA (γ-aminobutyric acid). All FNPA increased in lentils and peas. Light germination resulted in the highest α-amino adipic acid contents in beans, and the highest value of taurine in lentils. The highest FNPA content was found in peas after dark germination.

Link to the article

L’article Effects of different germination conditions on the contents of free protein and non-protein amino acids of commercial legumes est apparu en premier sur ETAP-LAB.

Sialorphin, a natural inhibitor of rat membrane-bound neutral endopeptidase that displays analgesic activity

Gregory — Tue, 01 Jul 2003 19:29:57 +0000

Sialorphin is an exocrine and endocrine signaling mediator, which has been identified by a genomic approach. It is synthesized predominantly in the submandibular gland and prostate of adult rats in response to androgen steroids and is released locally and systemically in response to stress. We now demonstrate that the cell surface molecule to which sialorphin binds in vivo in the rat kidney is the membrane-anchored neutral endopeptidase (neprilysin; NEP, EC 3.4.24.11). NEP plays an important role in nervous and peripheral tissues, as it turns off several peptide-signaling events at the cell surface. We show that sialorphin prevents spinal and renal NEP from breaking down its two physiologically relevant substrates, substance P and Met-enkephalin in vitro. Sialorphin inhibited the breakdown of substance P with an IC50 of 0.4-1 microM and behaved as a competitive inhibitor. In vivo, i.v. sialorphin elicited potent antinociceptive responses in two behavioral rat models of injury-induced acute and tonic pain, the pin-pain test and formalin test. The analgesia induced by 100-200 mcicrog/kg doses of sialorphin required the activation of mu- and delta-opioid receptors, consistent with the involvement of endogenous opioid receptors in enkephalinergic transmission. We conclude that sialorphin protects endogenous enkephalins released after nociceptive stimuli by inhibiting NEP in vivo. Sialorphin is a natural systemically active regulator of NEP activity. Furthermore, our study provides evidence that it is a physiological modulator of pain perception after injury and might be the progenitor of a new class of therapeutic molecules.

L’article Sialorphin, a natural inhibitor of rat membrane-bound neutral endopeptidase that displays analgesic activity est apparu en premier sur ETAP-LAB.

The delivery rate of dietary carbohydrates affects cognitive performance in both rats and humans

Gregory — Sat, 01 Feb 2003 19:29:25 +0000

RATIONALE:

Glucose is the main metabolic fuel of the brain. The rate of glucose delivery from food to the bloodstream depends on the nature of carbohydrates in the diet, which can be summarized as the glycaemic index (GI).

OBJECTIVES:

To assess the benefit of a low versus high GI breakfast on cognitive performances within the following 4 h.

METHODS:

The influence of the GI of the breakfast on verbal memory of young adults was measured throughout the morning in parallel to the assessment of blood glucose levels. The learning abilities of rats performing an operant-conditioning test 3 h after a breakfast-like meal of various GI was also examined.

RESULTS:

A low GI rather than high GI diet improved memory in humans, especially in the late morning (150 and 210 min after breakfast). Similarly, rats displayed better learning performance 180 min after they were fed with a low rather than high GI diet.

CONCLUSION:

Although performances appeared to be only remotely related to blood glucose, our data provide evidence that a low GI breakfast allows better cognitive performances later in the morning.

L’article The delivery rate of dietary carbohydrates affects cognitive performance in both rats and humans est apparu en premier sur ETAP-LAB.

Effects of ING-911, a tryptic hydrolysate from bovine Milk alpha S1-Casein on anxiety of Wistar male rats measured in the conditioned defensive burying paradigm and the elevated-plus maze test

Gregory — Wed, 01 Jan 2003 19:34:06 +0000

ING-911 is a tryptic hydrolysate from bovine milk that contains as a major component, a peptide corresponding to the 91-100 fragment of the α S1-casein. As diazepam (DZ), ING-911 was found to have an anticonvulsant activity in the pentylenetetrazole-induced seizures test. The aim of this study was to assess the effects of ING-911 on anxiety of Wistar male rats in two behavioural situations that were designed to elicit responses to aversive stimuli: the conditioned defensive burying paradigm and the elevated plus maze test. ING-911 was suspended in 0.3% methyl cellulose and administered p.o. at a dose of 15 mg/kg 60 min before testing. Control animals received the same volume of methyl cellulose. A third group was treated with diazepam (3 mg/kg, p.o., 60 min before testing) used as a reference anxiolytic substance. In the conditioned defensive burying paradigm, ING-911 and DZ induced a significant 40% reduction of the anxiety global score that is calculated from the probe burying duration, the number of head stretchings directed towards the probe and the percentage of approaches towards the probe followed by retreats. In the elevated plus maze test, DZ and ING-911 were found to decrease by 40% the percentage of closed arm entries compared to controls and to increase the percentages of open arm entries and time spent in the open arms (+103% and +54% for DZ, +118% and +49% for ING-911, respectively). DZ also induced a significant increase of the total arm entries (+63%) and the total number of head dipping (+189%) whereas ING-911 did not. In conclusion, the present data provide evidence that the bovine milk αS1-casein hydrolysate ING-911 displays a potent anxiolytic-like profile with a behavioural profile that is different from this observed with DZ.

Link to the article

L’article Effects of ING-911, a tryptic hydrolysate from bovine Milk alpha S1-Casein on anxiety of Wistar male rats measured in the conditioned defensive burying paradigm and the elevated-plus maze test est apparu en premier sur ETAP-LAB.

A new method of implanting orthotopic rat bladder tumor for experimental therapies

Gregory — Fri, 01 Nov 2002 19:33:31 +0000

We developed a model of orthotopic transplantation of bladder tumor cells in female Fischer rats using a new reproducible technique. After first performing the mechanical abrasion of a portion of the bladder urothelium with an Abrader inserted transurethrally via a catheter, we administered a suspension of 5-40 x 10(6) viable AY-27 tumor cells in sterile phosphate-buffered saline to the bladder cavity. This rapidly led to a tumor growth incidence of approximately 100%. The induced bladder tumors grew expansively into the bladder cavity from the surface (mucosa) and gradually invaded the submucosa, muscles, serosa and surrounding tissue (high-stage invasive transitional cell carcinoma). Size and staging were related to the quantity of tumor cells instilled into the bladder cavity. This model matches the characteristics of human bladder tumor more closely than other bladder cancer models induced with tumor cells. Moreover, it presents many advantages: the method is reproducible, tumors grow rapidly, they are directly attached to the bladder surface and they are always located on the bladder wall, in line with the urethra. This proves especially helpful for evaluating chemotherapeutic agents by different means such as in vivo fluorescence spectroscopy, a noninvasive method used in photodynamic therapy, or other methods designed to detect and treat transitional cell carcinoma.

L’article A new method of implanting orthotopic rat bladder tumor for experimental therapies est apparu en premier sur ETAP-LAB.

Determination of the maximal tumor:normal bladder ratio after i.p. or bladder administration of 5-aminolevulinic acid in Fischer 344 rats by fluorescence spectroscopy in situ

Gregory — Sun, 01 Sep 2002 19:32:52 +0000

The two major steps in our study on the treatment of bladder tumors by photodynamic therapy (PDT) were the development of a new bladder tumor model in Fischer rats by implantation of tumor cells and the use of fluorescence spectroscopy, a semi-quantitative and non-invasive method, in order to determine the time after general or local administration of a photosensitizer when the tumor:normal bladder ratio was at its highest. 5-Aminolevulinic acid (5-ALA) (250 mg/kg body weight) was injected i.p. or instilled directly into the bladder cavity for 1, 2 or 4 h and fluorescence was measured on normal and bladder tumor tissues every 30 min for 8-10 h after administration, with a special miniaturized optical-fiber captor. The better tumor:normal bladder ratios were 2.85+/-1.2 at 3.5 h after i.p. administration and 3.96+/-1.04 after bladder instillation for 4 h, respectively. These results were confirmed by fluorescence microscopy. PDT with the same dose of 5-ALA as in this pharmacokinetic study must also be carried out in order to compare the toxicity of the two administration routes of the photosensitizer and to determine which one is the better for this bladder tumor model.

L’article Determination of the maximal tumor:normal bladder ratio after i.p. or bladder administration of 5-aminolevulinic acid in Fischer 344 rats by fluorescence spectroscopy in situ est apparu en premier sur ETAP-LAB.

Induction of syngeneic intradermal and orthotopic epidermal carcinomas in hairless Skh-1 mice as a reproducible model for experiments

Gregory — Sun, 01 Sep 2002 19:32:13 +0000

Epidermoid carcinomas, clinically and histologically similar to human squamous cell carcinomas (SCC), were obtained in hairless Skh-1 mice. Tumor cells originated from chemically-induced skin cancers. We developed three models of orthotopic skin tumors: (1) intradermal injection of a tumor cell suspension, (2) superficial abrasion of the skin, cell grafting and application of a hydrocolloid dressing, (3) skin incision, seeding and application of a hydrocolloid dressing. Intradermal injection was 100% successful. Skin incision, displaying histological evidence of rapid invasive tumor growth, was 75% successful. Though skin tumor growth after abrasion was only 20% successful, the tumor histogenesis exactly imitated human SCC development. These carcinomas provide research models for further experiments such as photodynamic therapy or antiangiogenesis therapy.

L’article Induction of syngeneic intradermal and orthotopic epidermal carcinomas in hairless Skh-1 mice as a reproducible model for experiments est apparu en premier sur ETAP-LAB.

Nonprotein amino acids in edible lentil and garden pea seedlings.

Gregory — Thu, 20 Dec 2001 07:46:06 +0000

Commercial edible seedlings of garden pea (Pisum sativum L.) and lentil (Lens culinaris L.) contain high concentration of nonprotein amino acids and trigonelline. Both seedlings grown in the laboratory or purchased in a supermarket were studied by HPLC. Samples from both origins contained trigonelline, alpha-aminoadipic acid, homoserine, beta-(isoxazolin-5-on-2-yl)-alanine (BIA), and gamma-glutamyl-BIA. Garden pea seedlings also contained a uracil-alanine derivative (isowillardiine) in substantial amount. Some of these compounds such as BIA and alpha-aminoadipic acid have neurotoxic activity.

L’article Nonprotein amino acids in edible lentil and garden pea seedlings. est apparu en premier sur ETAP-LAB.

Identification and quantification of natural isoxazolinone compounds by capillary zone electrophoresis.

Gregory — Mon, 17 Dec 2001 10:18:02 +0000

A capillary zone electrophoresis (CZE) method that is specific, simple, rapid and also cheap was developed to analyse some natural UV-absorbing isoxazolinone compounds with toxic potential present in legume seedlings. The six most common natural isoxazolinone compounds were separated within 10 min with 25 mM potassium phosphate (pH 7.5) containing 8% 1-propanol as running buffer. A 60 cm coated fused-silica capillary (52.6 cm effective length x 75 microm I.D.), with an electric field of 375 V/cm at 30 degrees C was used. The limit of detection ranged from 0.01 mM (3.0 microg/ml) to 0.03 mM (7.7 microg/ml). Linearity between peak areas and concentrations ranging from 0.05 mM to 1.75 mM were determined for each isoxazolinone. The correlation coefficient was 0.9954 or greater. Both relative migration time and peak area were reproducible. The RSD of relative migration time is between 0.44 and 1.94% and RSD of peak area is between 1.26 and 6.86%. The concentrations of isoxazolinones in Lathyrus odoratus and L. sativus seedlings obtained by CZE were in agreement with the previous results from HPLC.

L’article Identification and quantification of natural isoxazolinone compounds by capillary zone electrophoresis. est apparu en premier sur ETAP-LAB.

Amino acids in seeds and seedlings of the genus Lens.

Gregory — Mon, 22 Oct 2001 09:36:57 +0000

The amino acid content of seeds and 4-day-old seedlings were studied in five species of lentil: Lens culinaris, L. orientalis, L. ervoides, L. nigricans and L. odemensis. Free amino acid and also total protein amino acid content after HCl hydrolysis were determined by HPLC. The nonprotein UV-absorbing amino acids were determined by capillary zone electrophoresis (CZE). The content of free protein amino acids in seeds varied among species and increased dramatically after germination. Asparagine is quantitatively most important in both seed and seedling. The content of free nonprotein amino acids is variable in seeds and seedlings. gamma-Hydroxyarginine, gamma-hydroxyornithine, alpha-aminobutyric acid and taurine were found in both seeds and seedlings. Homoarginine was found in four species but not in L. orientalis while gamma-aminobutyric acid (GABA), alpha-aminoadipic acid (alpha-aaa) and three isoxazolinone derivatives: beta-(isoxazolin-5-on-2-yl)-alanine (BIA), gamma-glutamyl-BIA (gamma-glu-BIA) and 2-carboxymethyl-isoxazolin-5-one (CMI) were found exclusively in the seedlings. CMI was identified for the first time in lentil species. Lathyrine, beta-(2-amino-pyrimidine-4-yl)-alanine, which was reported to be in the seeds of some Lathyrus species was confirmed to be present also in the seedling of L. culinaris (trace amount), L. nigricans and L. odemensis. Trigonelline (N-methyl-nicotinic acid), a plant hormone, is present both in seeds and seedlings in different concentrations except in L. ervoides. The different combination of nonprotein amino acids among the species gives indication of their genetic relationship and might partly explain the varying compatibility for interspecies crossing.

L’article Amino acids in seeds and seedlings of the genus Lens. est apparu en premier sur ETAP-LAB.

Reduction efficiency of the neurotoxin β‐ODAP in low‐toxin varieties of Lathyrus sativus seeds by solid state fermentation with Aspergillus oryzae and Rhizopus microsporus var chinensis

Gregory — Mon, 18 Dec 2000 10:32:04 +0000

Solid state fermentation of several low‐toxin varieties of grass pea (Lathyrus sativus L) seeds with Aspergillus oryzae and Rhizopus microsporus var chinensis removed the neurotoxin β‐ODAP (3‐N‐oxalyl‐L‐2,3‐diaminopropanoic acid) to a considerable degree from the seed meal. The detoxification efficiency was statistically significant and ranged from 52.4% (p < 0.01) to 82.2% (p < 0.001), which was lower than for a high‐toxin variety processed by the same fermentation procedure (94.8%, p < 0.001). While the content of β‐ODAP decreased, those of other free protein amino acids, especially glutamic acid, histidine, threonine, tyrosine, valine and lysine, increased dramatically in the fermented seeds. Efforts to remove the neurotoxin from Lathyrus sativus either by breeding or by food processing to obtain toxin‐free grass pea seeds have been made worldwide for several decades. The efficiencies of various reported processing methods are summarised and compared.

Link to the article

L’article Reduction efficiency of the neurotoxin β‐ODAP in low‐toxin varieties of Lathyrus sativus seeds by solid state fermentation with Aspergillus oryzae and Rhizopus microsporus var chinensis est apparu en premier sur ETAP-LAB.

Free amino acids present in commercially available seedlings sold for human consumption. A potential hazard for consumers.

Gregory — Thu, 27 Apr 2000 10:22:53 +0000

The importance of fresh seedlings for human consumption on European markets continues to increase. Although the contents of free amino acids and potentially toxic free nonprotein amino acids in these fresh and supposedly healthy seedlings is very different from those of the seeds, the crude composition is never mentioned on commercial packages. A commercial product containing seven different kinds of fresh seedlings including kamut, adzuki bean, chickpea, mungbean, pinto bean, garden pea, and lentil has been analyzed by HPLC. Per 100 g of fresh product, 548.2 mg of total free amino acids was found, of which 56.7 mg is free nonprotein amino acids including beta-(isoxazolin-5-on-2-yl)alanine, homoserine, and isowillardiine and the plant hormone trigonelline (N-methylnicotinic acid). The highest amounts of free nonprotein amino acids and trigonelline are found in garden pea (28.3 mg/100 g), mungbean (9.59 mg/100 g), and lentil (7.50 mg/100 g) seedlings. Trigonelline is present in all legume seedlings examined.

L’article Free amino acids present in commercially available seedlings sold for human consumption. A potential hazard for consumers. est apparu en premier sur ETAP-LAB.

Nutritional quality of toasted or dehulled and cold defatted rapeseed meal

Gregory — Fri, 02 Jul 1999 12:33:37 +0000

Rapeseed meal is an important protein source because of its well-balanced amino acid composition. However, its use in animal feeding is limited because of glucosinolates and a high fibre content. The aim of this study was to evaluate the nutritional quality of two products, a toasted industrial rapeseed meal with a low myrosinase and glucosinolate content and a dehulled rapeseed meal, with a low fibre content, which had been defatted at 50 °C.

An ad libitum food intake experiment was conducted with adult rats fed 200 g/kg protein diets based on casein or the rapeseed products. The food intake and body weight of rats fed casein or toasted rapeseed meal presscake diets were similar at the beginning of experiment and were still not significantly different after 8 days. From the start to the end of the experiment food intake of rats fed dehulled and defatted rapeseed meal presscake decreased significantly compared wrth rats fed casein. After 8 days, the boby weight of these rats had decreased significantly compared with the body weight of rats fed casein or toasted rapeseed meal presscake.

Both rapeseed meals differed in their prior treatment. Industrial treatment gave a toasted rapeseed meal presscake which had a good in vivo nutritional quality even if protein insolubility was high. Dehulling and defatting rapeseed, at moderate temperature, to preserve protein solubility, may not degrade myrosinase and glucosinolates sufficiently. We suggest that better nutritional quality could be obtained by both dehulling and toasting.

Link to the article

L’article Nutritional quality of toasted or dehulled and cold defatted rapeseed meal est apparu en premier sur ETAP-LAB.

Behavioral evaluation of visceral pain in a rat model of colonic inflammation

Gregory — Thu, 01 Apr 1999 19:36:13 +0000

A new rat model was established up to evaluate the antinociceptive effect of compounds in visceral pain. The test consisted in measuring the performance of rats in an aversive light stimulus avoidance experimental device. Rats with TNBS-induced colitis had a lower number of total active lever pressings and did not discriminate the active lever from the inactive one. Morphine (1 mg/kg, s.c.) and CI-977 (0.001 mg/kg, s.c.) treatment restored the level of pressing activity of animals and their ability to discriminate the active lever from the inactive one. Naloxone treatment antagonized the improvement of performance produced by morphine. The results obtained indicate that this behavioral paradigm may be used to evaluate the antinociceptive potential of compounds.

L’article Behavioral evaluation of visceral pain in a rat model of colonic inflammation est apparu en premier sur ETAP-LAB.

Induction of superficial bladder tumors in the female Fischer 344 rats with AY-27 tumor cells for the study of diffusion and localization of hemoglobin derived components (hematoporphyrin derivative) in view of photochemotherapy

Gregory — Fri, 01 Jan 1999 19:35:43 +0000

Photochemotherapy (PCT) consists in administration of a photosensitizer and subsequent irradiation of the tumor with visible light. Routinely, the photosensitizer is given intravenously (i.v.), but the major drawback of this procedure is the resulting skin photosensitivity. The goal of our study is to examine whether intravesical (i.b.) instillation of the photosensitizer for PDT of bladder cancer might be feasible in order to target the tumors and to avoid the photosensitization phenomenon. After first studying the biodistribution of hematoporphyrin derivative (HpD) in vivo in the rat bladder, two and four hours after intravesical administration, by fluorescence microscopy, we compared two different methods for the induction of superficial bladder tumors in rats with AY-27 tumor cell line in order to perform the same study on bladder tumors. The best results for the penetration depth of HpD in the normal bladder wall were obtained two hours after the bladder instillation where the photosensitizer was detected only in the bladder surface (urothelium and small part of the chorion). That’s why we must choose the most appropriate bladder tumor model in order to obtain superficial bladder tumors that mimic the clinical behavior of superficial bladder cancer in man. Both techniques used in this study gave a high tumor take rate in a short time (> 90%). But we really obtained superficial bladder tumors directly attached to the bladder surface with one of the two methods of tumor induction consisting in the abrasion of the bladder surface prior to the administration of the tumoral cells in the bladder cavity.

L’article Induction of superficial bladder tumors in the female Fischer 344 rats with AY-27 tumor cells for the study of diffusion and localization of hemoglobin derived components (hematoporphyrin derivative) in view of photochemotherapy est apparu en premier sur ETAP-LAB.

In Vivo and in Vitro Digestibility of Soybean, Lupine, and Rapeseed Meal Proteins after Various Technological Processes

Gregory — Fri, 19 Dec 1997 12:29:50 +0000

Anti-nutritional factors and technological processes may modify the nutritional quality of plant proteins. Heated rapeseed meal, soybean, and lupine proteins dried by various processes were used to compare in vivo methods of nutritional quality measurement such as protein efficiency ratio and true digestibility (TD) to in vitro methods such as pH-stat giving degree of hydrolysis (DH) and digestion cell giving nitrogen digestibility (ND). Combined methods taking into account amino acid score were as follows: PDCAAS (protein digestibility-corrected amino acid score) derived from TD, NDCAAS (nitrogen digestibility-corrected amino acid score), and DHCAAS (degree of hydrolysis-corrected amino acid score). Correlations (p < 0.001) were 0.81 (TD vs DH) and 0.88 (TD vs ND). PDCAAS was significantly (p < 0.001) correlated with DHCAAS or NDCAAS (r = 0.92 and 0.98, respectively). Time-consuming and expensive TD determination could be supplanted by both in vitro methods; DHCAAS and NDCAAS could replace PDCAAS.

Link to the article

L’article In Vivo and in Vitro Digestibility of Soybean, Lupine, and Rapeseed Meal Proteins after Various Technological Processes est apparu en premier sur ETAP-LAB.

Nutritional Value of Veal Bone Hydrolysate

Gregory — Mon, 15 Dec 1997 12:42:20 +0000

Industrial veal hydrolysate was produced enzymatically for possible use as a gelatin‐replacing ingredient for human consumption. Protein digestibility and nutritional value were determined in vitro and in vivo. Net protein ratio (= 2.65) and true digestibility (= 80.3) were compared with gelatin and caseinate. Protein digestibility was determined by pH‐stat method and cell dialysis. Amino acid composition including 4‐hydroxyproline, allowed determination of connective tissue, amino acid score and protein digestibility corrected amino acid score. High correlation was found between true digestibility and pH‐stat method (R²= 0.99). Meaty flavor and gelling properties of veal hydrolysate could make it useful for high‐quality soups, sauces and gravies.

Link to the article

L’article Nutritional Value of Veal Bone Hydrolysate est apparu en premier sur ETAP-LAB.

Effects of the light–dark cycle on a water tank social interaction test in mice.

Gregory — Mon, 24 Feb 1997 12:51:24 +0000

Mice were exposed to a water tank interaction test in which food could be obtained either by wading in the water or by attacking littermates. A tank with progressively rising water levels caused mice in groups of four to differentiate into those willing to wade (carrier mice) from those unwilling to wade (noncarrier mice). Noncarrier mice could only obtain food by stealing it from carrier mice or from other noncarrier mice. It was found that mice during the dark period of the light–dark cycle were more willing to wade in the search for food rather than attempt to steal food from other mice. Because mice are generally more active during the dark period, this result suggests that higher activity levels increase the willingness to share the work load, a form of altruism, rather than promote parasitic behavior and aggression.

L’article Effects of the light–dark cycle on a water tank social interaction test in mice. est apparu en premier sur ETAP-LAB.

Behavioral differentiation of mice exposed to a water tank social interaction test

Gregory — Wed, 27 Mar 1996 13:13:55 +0000

Male or female C57BL/6J mice were exposed to a water tank in which food could be obtained only by wading in the water towards a feeder. Behavioral differentiation occurred in that three distinct categories could be distinguished: major carriers (transporting over 80% of the food pellets), sporadic carriers (transporting less than 20% of the food pellets) and non-carriers. In the elevated + -maze, major carriers were more willing to explore open spaces than non-carriers. Sporadic carriers showed some evidence of the same tendency of decreased anxiety, but in a minor way. The willingness of mice to become carriers is associated with their willingness to explore novel areas. This test may be useful for the assessment of anxiolytic compounds in a social situation.

Link to the article

L’article Behavioral differentiation of mice exposed to a water tank social interaction test est apparu en premier sur ETAP-LAB.

Detoxication of rapeseed meal by Rhizopus Oligosporus sp‐T3: A first step towards rapeseed protein concentrate

Gregory — Mon, 25 Mar 1996 12:49:32 +0000

To obtain proteins from OO rapeseed meal for use in human food, a first step was realized by fermentation with Rhizopus oligosporus spT3. The meal’s fermentation during 40 h resulted in degradation of 84% of carbohydrates, 30% of lignin and other polyphenolic components indigestible by nonruminants, and 47% of total glucosinolates which are responsible for goitre. The fermentation improves the nutritional quality of rapeseed meal by degrading undesirable factors.

Link to the article

L’article Detoxication of rapeseed meal by Rhizopus Oligosporus sp‐T3: A first step towards rapeseed protein concentrate est apparu en premier sur ETAP-LAB.

Effects of MPTP on lever-pressing for light extinction in rats

Gregory — Fri, 01 Mar 1996 19:35:03 +0000

Rats were daily treated for seven days with 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) at a dose of 20 mg/kg/day, i.p. Seven days after treatment withdrawal, the rats were individually tested in a brightly lit apparatus containing two levers: an active lever allowing periods of darkness, and an inactive one. The test was performed over two consecutive days, in 20-min sessions. While control rats had a higher number of total active lever pressings than inactive lever pressings, this was not the case for MPTP-treated rats. Control rats decreased their useless active lever pressings and inactive lever pressings across the two sessions, but MPTP-treated rats did not do either. The absence of the differential effect in rats injected with MPTP may be due to a reduction in reinforcement mechanisms caused by the mild depletion of dopamine in the striatum.

L’article Effects of MPTP on lever-pressing for light extinction in rats est apparu en premier sur ETAP-LAB.

Diffusion and localization of hematoporphyrin derivative in the normal bladder wall of pig and rat after local administration

Gregory — Mon, 01 Jan 1996 19:34:33 +0000

Photodynamic therapy (PDT) consists in the administration of a photosensitizer and subsequent irradiation of the tumor with visible light. Routinely, the photosensitizer is given intravenously (i.v.), but the major drawback of this procedure is the resulting skin photosensitivity. The goal of our study was to examine whether intravesical (i.b.) instillation of the photosensitizer for PDT of bladder cancer might be feasible in order to target the tumors and to avoid the photosensitization phenomenon. After studying the normal bladder histology of pig and rat, not much described so far, we studied the diffusion and localization of hematoporphyrin derivative (HpD) in vitro on the pig bladder and the biodistribution of HpD in vivo in the rat bladder, two and four hours after intravesical administration, by spectrofluorimetry and fluorescence microscopy. We have the following results: (1) no diffusion through the pig bladder wall was detected; (2) the penetration depth of HpD into the pig bladder wall was 450 plus or minus 44 micrometers (n equals 8), including urothelium and chorion in totality and a small part of the muscles; (3) the penetration depth of HpD into the rat bladder wall was 55 plus or minus 9 micrometer (n equals 9) after two hours and 960 plus or minus 118 micrometer (n equals 9) after four hours, corresponding respectively to the totality of the urothelium and a small part of the chorion or almost completely in the bladder wall, a small part of the adventicia being excluded. In conclusion, intravesical instillation is feasible and, as superficial bladder cancer, especially carcinoma in situ particularly occur in the urothelium or in the chorion, a bladder instillation of two hours should be advantageous.

Link to the article

L’article Diffusion and localization of hematoporphyrin derivative in the normal bladder wall of pig and rat after local administration est apparu en premier sur ETAP-LAB.