Benoit Sion - Academia.edu (original) (raw)

Papers by Benoit Sion

Frontiers in Pharmacology, 2019

Bladder pain is frequently associated with bladder inflammation, as in conditions like interstiti... more Bladder pain is frequently associated with bladder inflammation, as in conditions like interstitial cystitis (IC), for which current analgesic therapies have limited efficacy. The antinociceptive effect of alpha-2-delta (α 2 δ) ligands on inflammation-associated visceral pain like that experienced in cystitis has been poorly investigated. To investigate the effect of pregabalin (PGB), an α 2 δ ligand, we evaluated its impact on mechanical hyperalgesia in a mouse model of cystitis induced by cyclophosphamide (CYP). We further studied its effect on inflammation and NF-kB pathway activation. Acute cystitis was induced by intraperitoneal injection of 150 mg kg −1 of CYP in C57Bl/6J male mice. PGB was subcutaneously injected (30 mg kg −1) 3 h after CYP injection. The effect of PGB on CYP-induced mechanical referred hyperalgesia (abdominal Von Frey test), inflammation (organ weight, cytokine production, α 2 δ subunit level, NF-kB pathway activation) were assessed 1 h after its injection. In parallel, its effect on cytokine production, α 2 δ subunit level and NF-kB pathway activation was assessed in vitro on peritoneal exudate cells (PECs) stimulated with LPS. PGB treatment decreased mechanical referred hyperalgesia. Interestingly, it had an anti-inflammatory effect in the cystitis model by reducing pro-inflammatory cytokine production. PGB also inhibited NF-kB pathway activation in the cystitis model and in macrophages stimulated with LPS, in which it blocked the increase in intracellular calcium. This study shows the efficacy of PGB in hypersensitivity and inflammation associated with cystitis. It is therefore of great interest in assessing the benefit of α 2 δ ligands in patients suffering from cystitis.

International Neuroscience Conference, Jul 1, 2020

IEEE EUROCON 2017 -17th International Conference on Smart Technologies, 2017

This paper presents a high resolution method for analyzing of electrophysiological activities usi... more This paper presents a high resolution method for analyzing of electrophysiological activities using Matrix Pencil Method (MPM). This approach identifies measured signal from nerves to better understanding the functional organization of neuronal ensembles that form the peripheral nerves or the cerebral cortex. Matrix Pencil Method which is used to extract original signals and benefits from minimum exponential functions while having excellent reproducibility feature. MPM also can eliminate the noise part of the system and return pure original signal. In this paper, MPM is used to reconstruct recorded action potential from cockroach by using Matlab environment which shows less than 4% error.

5-HT2A Receptors in the Central Nervous System, 2018

Serotonin (5-hydroxytryptamine, 5-HT) is a key modulator of spinal nociceptive transmission. Amon... more Serotonin (5-hydroxytryptamine, 5-HT) is a key modulator of spinal nociceptive transmission. Among 5-HT receptors, the 5-HT2A subtype plays a critical role in the modulation of nociceptive information. Both pro- and antinociceptive effects of 5-HT2A receptor activation have been reported but converging evidence indicates an excitatory role for peripheral 5-HT2A receptors on pain transmission in acute, sub-chronic and chronic pain conditions. The central effects of 5-HT2A agonists which produce either anti-hyperalgesic or anti-allodynic effect seem to depend on the pathophysiology of pain. Neverthless, some data indicate that 5-HT acting drugs such as selective serotonin reuptake inhibitor (SSRI) antidepressants involve the 5-HT2A receptor to produce analgesia and that restoring 5-HT2A receptor functionality may contribute to enhance the analgesic efficacy of SSRI in metabolic and traumatic neuropathic pain.

INTRODUCTION To better understand the physiopathological mechanisms of pain or to evaluate the ef... more INTRODUCTION To better understand the physiopathological mechanisms of pain or to evaluate the effectiveness of analgesic substances, response of unitary neurons in animal model or cortical response in human to peripheral stimulations can be analyzed using electrophysiological recordings such as the electroneurogram (ENG) or electroencephalogram (EEG). The analysis of ENG involves measuring the spike frequency, the amplitude and nerve conduction velocity after applying peripheral stimulations but little is known about the spontaneous nerve activity. In peripheral nerves, we try to extract predictive signals of activity in primary afferent fibers by distinguishing the type of nociceptors AMH (Aδ myelinated fibers) and MHC (unmyelinated C fibers). The method used in this work is called Matrix Pencil Method (MPM) and is usually referred to as a high-resolution technique. The method provides one to identify non-stationary signals, even in the presence of numerical or measurement noise, ...

2018 EMF-Med 1st World Conference on Biomedical Applications of Electromagnetic Fields (EMF-Med), 2018

Stimulus artifact affecting electrophysiological recordings makes neural response analysis quite ... more Stimulus artifact affecting electrophysiological recordings makes neural response analysis quite difficult. To analyze response with a maximum of precision, one needs to remove firstly the stimulus artifact without causing a neural response distortion. This paper introduces a new method of stimulus artifact removal based on its reconstruction with Matrix Pencil method.

2018 26th International Conference on Software, Telecommunications and Computer Networks (SoftCOM), 2018

The paper deals with a novel technique to identify the artifact shape and reduce residual threat ... more The paper deals with a novel technique to identify the artifact shape and reduce residual threat during its removal. The method is based on the stimulus artifact reconstruction by using the high resolution Matrix Pencil method. The proposed technique has proved to be efficient in eliminating the stimulus artifact from signals which were recorded on a rat’s sciatic nerve.

Fundamental & Clinical Pharmacology, 2021

The importance of circadian rhythm dysfunctions in the pathophysiology of neurological diseases h... more The importance of circadian rhythm dysfunctions in the pathophysiology of neurological diseases has been highlighted recently. Chronopharmacology principles imply that tailoring the timing of treatments to the circadian rhythm of individual patients could optimize therapeutic management. According to these principles, chronopharmacology takes into account the individual differences in patients’ clocks, the rhythmic changes in the organism sensitivity to therapeutic and side effects of drugs, and the predictable time variations of disease. This review examines the current literature on chronopharmacology of neurological diseases focusing its scope on epilepsy, Alzheimer and Parkinson diseases, and neuropathic pain, even if other neurological diseases could have been analyzed. While the results of the studies discussed in this review point to a potential therapeutic benefit of chronopharmacology in neurological diseases, the field is still in its infancy. Studies including a sufficiently large number of patients and measuring gold standard markers of the circadian rhythmicity are still needed to evaluate the beneficial effect of administration times over the 24‐hour day but also of clock modulating drugs.

Actualités Pharmaceutiques, 2018

Gut Microbes, 2017

Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD) are related gastrointestinal ... more Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD) are related gastrointestinal disorders characterized by abdominal pain associated with colonic hypersensitivity (CHS). Studies in humans have reported an abnormal colonization of Adherent-Invasive E. coli (AIEC) in the ileum of Crohn's disease (CD) patients associated with overexpression of the bacterial colonizing receptor CEACAM6. The aim of the present study was to investigate whether AIEC reference strain LF82 could induce intestinal impairment during infectious and/or post-infectious periods and subsequently the development of CHS. Transgenic mice overexpressing human CEACAM6 protein (TG) and their wild-type littermates were gavaged by CD-associated AIEC bacteria (reference strain LF82) or PBS for 3 d. Colonic hypersensitivity was assessed by colorectal distension (CRD) test during infectious (D4) and post-infectious periods (D21). Several markers of intestinal inflammation were monitored and the colonic expression of purinergic P2X receptors was quantified. At D4, an increased visceromotor response (VMR) to the CRD test was observed in TG mice infected with CDassociated AIEC LF82 in comparison with non-infected TG mice and persisted in a subgroup of infected animals at D21 after bacteria clearance. Increased VMR was associated with low-grade intestinal inflammation, increased intestinal permeability and expression of P2X 3, 4 and 7. This study shows that certain susceptible hosts infected with CD-associated AIEC bacteria can develop persistent CHS associated with low-grade inflammation and increased P2X receptors expression. Thus, CD-associated AIEC infection in CEACAM6 transgenic mice could be used as a novel postinfectious mouse model mimicking quiescent IBD with IBS-like symptoms such as visceral pain.

Pharmacological research, Jan 20, 2016

Antidepressants are one of the first line treatments for neuropathic pain but their use is limite... more Antidepressants are one of the first line treatments for neuropathic pain but their use is limited by the incidence and severity of side effects of tricyclics and the weak effectiveness of selective serotonin reuptake inhibitors (SSRIs). Serotonin type 2A (5-HT2A) receptors interact with PDZ proteins that regulate their functionality and SSRI efficacy to alleviate pain. We investigated whether an interfering peptide (TAT-2ASCV) disrupting the interaction between 5-HT2A receptors and associated PDZ proteins would improve the treatment of traumatic neuropathic allodynia. Tactile allodynia was assessed in spinal nerve ligation-induced neuropathic pain in rats using von Frey filaments after acute treatment with TAT-2ASCV and/or 5-HT2A receptor agonist, alone or in combination with repeated treatment with fluoxetine. In vivo microdialysis was performed in order to examine the involvement of GABA in TAT-2ASCV/fluoxetine treatment-associated analgesia. TAT-2ASCV (100ng, single i.t. injecti...

Journal of Neurogastroenterology and Motility, 2017

Background/Aims Human gut microbiota harbors numerous metabolic properties essential for the host... more Background/Aims Human gut microbiota harbors numerous metabolic properties essential for the host's health. Increased intestinal transit time affects a part of the population and is notably observed with human aging, which also corresponds to modifications of the gut microbiota. Thus we tested the metabolic and compositional changes of a human gut microbiota induced by an increased transit time simulated in vitro. Methods The in vitro system, Environmental Control System for Intestinal Microbiota, was used to simulate the environmental conditions of 3 different anatomical parts of the human colon in a continuous process. The retention times of the chemostat conditions were established to correspond to a typical transit time of 48 hours next increased to 96 hours. The bacterial communities, short chain fatty acids and metabolite fingerprints were determined. Results Increase of transit time resulted in a decrease of biomass and of diversity in the more distal compartments. Short chain fatty acid analyses and metabolite fingerprinting revealed increased activity corresponding to carbohydrate fermentation in the proximal compartments while protein fermentations were increased in the lower parts. Conclusions This study provides the evidence that the increase of transit time, independently of other factors, affects the composition and metabolism of the gut microbiota. The transit time is one of the factors that explain some of the modifications seen in the gut microbiota of the elderly, as well as patients with slow transit time.

Http Www Theses Fr, 1991

Des cellules hypophysaires de rats cultivees en agregats, apres incorporation de #3#5 methionine,... more Des cellules hypophysaires de rats cultivees en agregats, apres incorporation de #3#5 methionine, sont stimulees en perifusion par des pulses de gnrh. Les proteine secretees sont separees par electrophorese. Le gnrh provoque la liberation d'au moins 13 proteines cosecretees avec la lh. Les liberations du gp87 (secretogranine ii) et de la b2 sont fortement amplifiees (proteines de masse moleculaire 87 et 80 dka). Leurs secretions sont gnrh dose-dependantes. La secretion du gp87 depend de la liaison du gnrh a son recepteur. Un dosage immunologique du gp87 a ete realise. Pour des temps de stimulation de courte duree, les quantites secretees de gp87 sont proportionnelles a celles de la lh et leurs cinetiques de secretion paralleles. Les quantites de gp87 total secrete ne decroissent pas en fonction des pulses de gnrh contrairement a celles de gp87 radioactif. Une stimulation de longue duree provoque une secretion biphasique du gp87 et une augmentation du rapport gp87 secrete/lh secretee. La liberation du gp87 est egalement provoquee par le trh. Le crf et le gnrh provoque une faible liberation aspecifique du gp87. Apres 24 heures d'action l'stradiol augmente les quantites du gp87 secretees durant les pulses de gnrh sans modifier celles de la h, et la dht inhibe dans les memes proportions leurs secretions. Apres 72 heures de traitement, l'stradiol augmente et le dht diminue les quantites de gp87 intracellulaire

The FASEB Journal, 2016

HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Journal of Chromatography B: Biomedical Sciences and Applications, 2000

A high-performance liquid chromatographic method coupled with light-scattering detection for the ... more A high-performance liquid chromatographic method coupled with light-scattering detection for the separate and accurate quantification of cholesterol and main phospholipid classes was applied to human spermatozoa and seminal plasma (SP). This method is based on normal-phase chromatography with silica gel as stationary phase and a ternary gradient with hexane, mixtures of chloroform-methanol and water as mobile phase. Lipids are separated with a good resolution and a high 6 reproducibility. About 5?10 spermatozoa or 25 ml of seminal plasma are sufficient to accurate quantitative analysis of phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidycholine (PC), sphingomyelin 8 (SM) and cholesterol. PC is the predominant phospholipid class in spermatozoa (10268 nmol / 10 spermatozoa) whereas SM is the major in the SP (16366 nmol / ml). Both in spermatozoa and SP, PI is the minor class of the phospholipids (1261 8 nmol / 10 spermatozoa and 2462 nmol / ml). In conclusion, this method offers interesting perspectives for analysis of sperm lipid composition in semen samples with low quantities of spermatozoa.

Reproductive Biology and Endocrinology, 2015

Background: Cryopreservation of ovarian tissue can be used to preserve the fertility of patients ... more Background: Cryopreservation of ovarian tissue can be used to preserve the fertility of patients who are about to receive treatment(s) that could compromise their future ovarian function. Here we evaluate the effectiveness of a vitrification protocol by carrying out a systematic comparison with a conventional slow-freezing method on human ovarian tissue. Methods: Human ovarian samples (mean age 28.0 ± 1.1 years) were processed in parallel for each cryopreservation procedure: vitrification and slow-freezing. Following warming/thawing, histological observations and a TUNEL assay in ovarian follicles were performed and compared to unfrozen control. Results: Both cryopreservation protocols gave comparable histological outcomes. Percentage of intact follicles was 83.6 % following vitrification in a 1.5 M 1,2-propanediol (PrOH), 1.5 M ethylene glycol (EG) and 0.5 M raffinose solution, 80.7 % after slow-freezing in 1.5 M PrOH and 0.025 M raffinose, and 99.6 % in fresh tissue. Follicle density was unchanged by vitrification (0.6 follicles/mm2) or slow-freezing (0.5 follicles/mm2) compared to fresh tissue (0.7 follicles/mm2). Percentage of follicles with DNA fragmentation was not statistically different in vitrified (20.8 %) or slow-frozen (31.3 %) tissues compared to the unfrozen control (35.0 %). There was no difference in proportion of stroma cells with DNA fragmentation in vitrified (6.4 %) and slow-frozen (3.7 %) tissues compared to unfrozen tissue (4.2 %). Conclusions: This vitrification protocol enables good preservation of ovarian quality post-warming. The evaluation of endocrine function after vitrification need to be perform in a higher cohort to evaluate if this protocol may offer a relevant alternative to conventional slow-freezing for the cryopreservation of human ovarian tissue.

Diabetes, 2012

Negative regulators of white adipose tissue (WAT) expansion are poorly documented in vivo. Prosta... more Negative regulators of white adipose tissue (WAT) expansion are poorly documented in vivo. Prostaglandin F2α (PGF2α) is a potent antiadipogenic factor in cultured preadipocytes, but evidence for its involvement in physiological context is lacking. We previously reported that Akr1b7, an aldo-keto reductase enriched in adipose stromal vascular fraction but absent from mature adipocytes, has antiadipogenic properties possibly supported by PGF2α synthase activity. To test whether lack of Akr1b7 could influence WAT homeostasis in vivo, we generated Akr1b7−/− mice in 129/Sv background. Akr1b7−/− mice displayed excessive basal adiposity resulting from adipocyte hyperplasia/hypertrophy and exhibited greater sensitivity to diet-induced obesity. Following adipose enlargement and irrespective of the diet, they developed liver steatosis and progressive insulin resistance. Akr1b7 loss was associated with decreased PGF2α WAT contents. Cloprostenol (PGF2α agonist) administration to Akr1b7−/− mice ...

Biology of Reproduction, 1994

Among monoclonal antibodies (mAb) selected after the immunization of mice with human ejaculated s... more Among monoclonal antibodies (mAb) selected after the immunization of mice with human ejaculated spermatozoa, mAb 19G9 (IgG,kappa) was found by immunoperoxidase staining to label most of the acrosome of human spermatozoa permeabilized with methanol-acetone. The antigen was poorly expressed on the surface of fresh ejaculated sperm, but was detectable on most viable sperm after 5-h incubation in medium containing human serum albumin (HSA) followed by 30-min incubation with the calcium ionophore A23187. This treatment resulted in acrosomal loss. Immunoelectron microscopy labeling with 19G9 mAb localized the antigen within the acrosome. Immunocytochemistry on testis sections showed that antigen was located in the round spermatids within the adluminal compartment of the seminiferous epithelium. Western blotting of sperm extract proteins showed that sperm intra-acrosomal antigen (SIAA) recognized by I9G9 mAb had a polymorphism of immunogenic peptides from 16 to 35 kDa. Most of the antigenic peptides possessed an isoelectric point of approximately 5. When spermatozoa were treated with a series of protease inhibitors, the polymorphism of immunogenic peptides was reduced, suggesting that the multiple form of the antigen was due, at least in part, to proteolytic processing. In the testis, only a single peptide band of 35 kDa was detected with mAb 19G9. Studies of human tissue specificity by Western blotting showed that the epitope recognized by I9G9 mAb was present solely in ejaculated spermatozoa and the testis. 19G9 mAb did not agglutinate or immobilize sperm but inhibited the penetration of zona-free hamster ova by human sperm.