Neurodegeneration, oxidative stress and lipid metabolism plasma biomarkers to differentiate Parkinson's disease from atypical parkinsonian syndromes.

INTRODUCTION: The identification of blood biomarkers appears to be a means of improving diagnosis accuracy in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS). We, therefore, evaluate the performance of neurodegeneration, oxidative stress and lipid metabolism plasma biomarkers to distinguish PD from APS. METHODS: This was a monocentric study with a cross-sectional design. Plasma levels and discriminating power of neurofilament light chain (NFL), malondialdehyde (MDA) and 24S-Hydroxycholesterol (24S-HC) were assessed in patients with clinical diagnoses of PD or APS. RESULTS: In total, 32 PD cases and 15 APS cases were included. Mean disease durations were 4.75 years in PD group and 4.2 years in APS group. Plasma levels of NFL, MDA and 24S-HC differed significantly between the APS and PD groups (P=0.003; P=0.009; P=0.032, respectively). NFL, MDA and 24S-HC discriminated between PD and APS (AUC=0.76688; AUC=0.7375; AUC=0.6958, respectively). APS diagnosis significantly increased with MDA level≥23.628nmol/mL (OR: 8.67, P=0.001), NFL level≥47.2pg/mL (OR: 11.92, P<0.001) or 24S-HC level≤33.4pmol/mL (OR: 6.17, P=0.008). APS diagnosis considerably increased with the combination of NFL and MDA levels beyond cutoff values (OR: 30.67, P<0.001). Finally, the combination of NFL and 24S-HC levels, or MDA and 24S-HC levels, or all three biomarkers' levels beyond cutoff values systematically classified patients in the APS group. CONCLUSION: Our results suggest that 24S-HC and especially MDA and NFL could be helpful for differentiating PD from APS. Further studies will be needed to reproduce our findings on larger, prospective cohorts of patients with parkinsonism evolving for less than 3 years.

Deterministic Limit of Intracellular Calcium Spikes.

In nonexcitable cells, global Ca^{2+} spikes emerge from the collective dynamics of clusters of Ca^{2+} channels that are coupled by diffusion. Current modeling approaches have opposed stochastic descriptions of these systems to purely deterministic models, while both paradoxically appear compatible with experimental data. Combining fully stochastic simulations and mean-field analyses, we demonstrate that these two approaches can be reconciled. Our fully stochastic model generates spike sequences that can be seen as noise-perturbed oscillations of deterministic origin, while displaying statistical properties in agreement with experimental data. These underlying deterministic oscillations arise from a phenomenological spike nucleation mechanism.

A review of psychosocial factors and stroke: A new public health problem.

The role of psychosocial factors (PSF) in increased risk of stroke is a novel public health challenge, but unclear definitions for PSF and the multiple stroke subtypes have led to inconsistent reports. A review of this issue is therefore warranted. METHODS: Several databases were used for this narrative systematic review (Medline, Embase and Cochrane Library). Two independent reviewers evaluated articles from between 2001 and 2018 on the themes of PSF and stroke/transient ischemic attack (TIA). PSF criteria were job strain, psychological interpersonal and behavioral stress, and social deprivation. Ischemic and hemorrhagic stroke and TIA subtypes were also identified. RESULTS: Forty-five cohorts, five case-control studies and two meta-analyses were included. Despite mixed results, PSF were associated with an increased risk of ischemic and hemorrhagic stroke in populations of all ages, and more predominantly in women. CONCLUSION: This broad review shows that the presence of PSF is associated with an increased risk stroke and TIA. As such, PSF must figure in both public health policy and stroke prevention programs, similar to other established metabolic and environmental factors.

Prevalence and factors predictive of full stomach in elective and emergency surgical patients: a prospective cohort study.

Background: This prospective observational study sought to assess the rate of full and empty stomach in elective and emergency patients and to determine the factors associated with full stomach. Methods: Non-premedicated patients were consecutively included between May 2014 and October 2014. Ultrasound examination of the gastric antrum was performed by an operator blinded to the history of the patient. It included measurement of the antral cross-sectional area, performed in the supine position with the head of the bed elevated to 45°, and qualitative assessment of the gastric antrum, performed in both semirecumbent and right lateral decubitus positions. Full stomach was defined by the appearance of any gastric content in both positions (Grade 2). Empty stomach was defined either by empty antrum in both positions (Grade 0) or by empty antrum in the semirecumbent position only (Grade 1) with measured antral area <340 mm2. The combination of Grade 1 and antral area >340 mm2 defined intermediate stomach. Logistic regression analyses were performed for the identification of factors associated with full stomach. Results: Four hundred and forty patients were analysed. The prevalence of full stomach was 5% (95% confidence interval: 2­9) in elective patients and 56% (95% confidence interval: 50­62) in emergency patients (P<0.0001). Obesity, diabetes mellitus, emergency surgery, and preoperative consumption of opiates were independent factors predictive of full stomach. Conclusions: The results suggest that preoperative ultrasound assessment of gastric content should be performed in all emergency patients, and in elective patients with identified predictive factors for full stomach.

Ultrasonographic gastric volume before unplanned surgery.

We aimed to measure gastric antral cross-sectional area with ultrasound and estimate the gastric volume of 300 patients before unplanned surgery, fasted for at least six hours. Measurements were successfully recorded in 263 semi-recumbent patients. The median (IQR [range]) area was 333 (241-472 [28-1803]) mm2 and the mean (SD) estimated volume was 45.8 (34.0) ml. The area exceeded 410 mm2 in 92/263 (35%) measurements. Body mass index and morphine administration were associated with larger gastric areas on multivariable linear regression analysis, with beta coefficient (95%CI) 0.02 (0.01-0.04), p = 0.01, 0.23 (0.01-0.46), p = 0.04, respectively. Fasting time was not associated with gastric area and therefore could not substitute for ultrasound measurements in this cohort.

[NEW SURGICAL APPROACH IN PRIMARY OPEN-ANGLE GLAUCOMA: XEN GEL STENT A MINIMALLY INVASIVE TECHNIQUE]. / NOUVELLE APPROCHE CHIRURGICALE DANS LE GLAUCOME À ANGLE OUVERT: le Xen Gel Stent, une technique micro-invasive.

Primary open-angle glaucoma is a progressive ocular disease affecting adults and associated with visual field defect. The aim of its treatment is to lower the ocular pressure by means of ocular drops, laser or surgery. To date, traditional surgical techniques still remain quite invasive, but recent research efforts have been made with a view to develop minimally invasive techniques. The Xen Gel Stent is one of them. It allows a safe and efficient lowering of ocular pressure by creating a sub-conjunctival flow, following an ab interno procedure that highly preserves the architecture of the treated eye.

How to better improve the treatment and outcomes of HCV in psychiatric patients: review of a Belgian monocentric psychiatric center.

Introduction: Hepatitis C (HCV) is one of the major worldwide infections with 58 million infected persons in the world. HCV can lead to chronic liver disease, cirrhosis, and cancer. These past few years, clinical progress allowed a curative rate of 95% of the patients. There are still populations in which, treating the disease is more difficult, especially psychiatric patients, when substance abuse, psychiatric disorders are important risks factors for getting HCV. With the WHO organization establishing goals for clinical management and treatment of HCV, it is important to target where the difficulties lie in getting a better treatment program for those populations. Aim: Try to highlight the challenges of treating a certain group of patients compare to the general population. Method: This is a cross sectional monocentric study. 79 patients from a mental facility were included between 2012 and 2022. Inclusion criteria were: >18 years old, an active viral HCV infection. Results: 34.7% of patients with a positive PCR were treated with a significant difference between the closed psychiatric unit and the open one (66.5 vs 22.6%, p<.05). There was an 82.4% eradication rate (Sustained Viral Response at 3 months). There were significantly more schizophrenic disorders in the closed unit and significantly more alcohol abuse in the open one. Conclusion: Treatment of HCV in a psychiatric population is feasible with eradication rate equivalent at those in the general population. Patients with more severe mental illness are better treated in the configuration of a closed psychiatric unit.

Culture and Immunomodulation of Equine Muscle-Derived Mesenchymal Stromal Cells: A Comparative Study of Innovative 2D versus 3D Models Using Equine Platelet Lysate.

Muscle-derived mesenchymal stromal cells (mdMSCs) hold great promise in regenerative medicine due to their immunomodulatory properties, multipotent differentiation capacity and ease of collection. However, traditional in vitro expansion methods use fetal bovine serum (FBS) and have numerous limitations including ethical concerns, batch-to-batch variability, immunogenicity, xenogenic contamination and regulatory compliance issues. This study investigates the use of 10% equine platelet lysate (ePL) obtained by plasmapheresis as a substitute for FBS in the culture of mdMSCs in innovative 2D and 3D models. Using muscle microbiopsies as the primary cell source in both models showed promising results. Initial investigations indicated that small variations in heparin concentration in 2D cultures strongly influenced medium coagulation with an optimal proliferation observed at final heparin concentrations of 1.44 IU/mL. The two novel models investigated showed that expansion of mdMSCs is achievable. At the end of expansion, the 3D model revealed a higher total number of cells harvested (64.60 ± 5.32 million) compared to the 2D culture (57.20 ± 7.66 million). Trilineage differentiation assays confirmed the multipotency (osteoblasts, chondroblasts and adipocytes) of the mdMSCs generated in both models with no significant difference observed. Immunophenotyping confirmed the expression of the mesenchymal stem cell (MSC) markers CD-90 and CD-44, with low expression of CD-45 and MHCII markers for mdMSCs derived from the two models. The generated mdMSCs also had great immunomodulatory properties. Specific immunological extraction followed by enzymatic detection (SIEFED) analysis demonstrated that mdMSCs from both models inhibited myeloperoxidase (MPO) activity in a strong dose-dependent manner. Moreover, they were also able to reduce reactive oxygen species (ROS) activity, with mdMSCs from the 3D model showing significantly higher dose-dependent inhibition compared to the 2D model. These results highlighted for the first time the feasibility and efficacy of using 10% ePL for mdMSC expansion in novel 2D and 3D approaches and also that mdMSCs have strong immunomodulatory properties that can be exploited to advance the field of regenerative medicine and cell therapy instead of using FBS with all its drawbacks.

Recovery after an intermittent test.

The purpose of this study was to analyse the impact of an intermittent test reproducing the soccer running activity profile on physical performance, subjective ratings and biochemical parameters throughout 72 h recovery. 8 professional soccer players performed the intermittent test on a non-motorised treadmill and data was collected before, immediately after, 24, 48 and 72 h after the test. Squat jump (SJ), countermovement jump (CMJ), peak isometric force (IFpeak), 6-s sprint, repeated sprints test (RS), perceptual ratings (fatigue, muscle soreness, stress), creatine kinase ([CK]) and uric acid ([UA]) were analyzed. After the test, a mean reduction in countermovement jump performance of -8.2% (CI: -12.9 to -3.4, p<0.01) was observed, while perceived fatigue (+2.1±1.7 a.u.; p<0.05), perceived muscle soreness (+1.8±1.5 a.u.; p<0.05), perceived stress (+1.6±1.5 a.u.; p<0.05), creatine kinase (+171±77 IU x l(-1); p<0.01) and uric acid (+168±89 Umol x l(-1); p<0.01) concentrations were significantly increased relative to baseline. No significant effect was found for SJ, IFpeak, 6-s sprint, RS immediately after and throughout the 72 h following the test. In conclusion, soccer running performance does not appear to be the main cause of post soccer match-induced fatigue. Physical data provided by video match analysis systems is insufficient to accurately estimate the level of match fatigue.

The petrosal artery and its variations: a comprehensive review and anatomical study with application to skull base surgery and neurointerventional procedures.

BACKGROUND: The petrosal artery supplies several structures at the skull base and is often the focus of various neurointerventional procedures. Therefore, knowledge of its anatomy and variations is important to surgeons and interventionalists. MATERIALS AND METHODS: Twenty latex injected cadaveric heads (40 sides) underwent microsurgical dissection of the petrosal artery. Documentation of the course of the artery and its branches were made. Measurements of the petrosal artery's length and diameter were performed using microcallipers. RESULTS: A petrosal artery was identified on all sides. The mean length and diameter of the artery within the middle cranial fossa was 2.4 cm and 0.38 mm, respectively. Branches included the following: dural, ganglionic, V3 branches, branches extending through the foramen ovale, branches directly to the greater petrosal and lesser petrosal nerves, branches to the floor of the hiatus of the greater and lesser petrosal nerves, branch to the arcuate eminence, and superior tympanic artery. No statistically significant differences were noted between male and female specimens, but right-sided petrosal arteries were in general, larger in diameter than left sides. CONCLUSIONS: A thorough anatomical knowledge of the petrosal artery and to its relationship to the facial nerve and other neurovascular structures is necessary to facilitate effective endovascular treatment and to preclude facial nerve complications.

Are physical performance and injury risk in a professional soccer team in match-play affected over a prolonged period of fixture congestion?

In this study, the effects of a prolonged period of fixture congestion (8 successive official matches in 26 days) on physical performance and injury risk and severity in a professional soccer team were investigated. Computerised motion-analysis was used to analyse the overall distance covered and that run at light- (0.0-11.0 km·h - 1); low- (11.1-14.0 km·h - 1); moderate- (14.1-19.7 km·h - 1) and high-intensities (≥19.8 km·h - 1) for the team as a whole. Distances were measured in metres per minute. Information on match injuries was recorded prospectively. The overall distance covered varied across successive matches (p<0.001) as more distance was run in games 4 and 7 compared to 2 and 3, respectively (126.6 ± 12.3 m·min - 1 and 125.0 ± 13.2 m·min - 1 vs. 116.0 ± 8.0 m·min - 1 and 115.5 ± 11.0 m·min - 1). Distance run in light-intensity exercise also varied (p<0.001) as more distance was covered in game 4 vs. 1, 2, 3, 5 and 6 (75.5 ± 3.8 m·min - 1 vs. 70.6 ± 2.4 m·min - 1, 71.8 ± 3.4 m·min - 1, 69.3 ± 2.6 m·min - 1, 71.5 ± 3.1 m·min - 1, and 70.3 ± 2.8 m·min - 1) and in game 8 vs. game 3 (73.1 ± 3.8 vs. 69.3 ± 2.6 m·min - 1), respectively. When comparing match halves, there were no differences across games in overall or high-intensity distance covered and performance in these measures was similar for matches played before, during and after this period. Globally, no difference over the 8 games combined was observed between the reference team and opponents in any of the performance measures whereas the overall distance covered and that in low- (both p<0.001) and high-intensity running (p=0.040) differed in individual games. The incidence of match injury during the congested fixture period was similar to rates reported outside this period but the mean lay-off duration of injuries was substantially shorter during the former (p<0.05). In summary, while the overall distance run and that covered at lower intensities varied across games, high-intensity running performance and injury risk were generally unaffected during a prolonged period of fixture congestion. These results might be linked to squad rotation and post-match recovery strategies in place at the present club.

Hyperoxia does not accelerate quadriceps muscle deoxygenation kinetics at the onset of heavy exercise cycle.

AIM: The aim of this study was to determine whether an increase in O2 availability induces an alteration of the balance between O2 consumption ((V)O2) and O2 delivery ((Q)O2) at the muscle level. For that, we examined the effect of moderate hyperoxia on muscle deoxygenation kinetics at the onset of heavy-intensity cycling exercise. METHODS: Eight young male adults performed step transitions from 35 W to heavy-intensity exercise corresponding to a power output half-way between the first ventilatory threshold and (V)O2max in normoxia and in hyperoxia (FIO2=0.30). Muscle deoxygenation (HHb) and total hemoglobin (Hbtot) were monitored continuously by near-infrared spectroscopy. HHb data were fit with a mono-exponential model from the onset of exercise up to 90 seconds. RESULTS: Hyperoxia neither altered the delay before the increase in HHb (normoxia: 10.7±1.8 s vs. hyperoxia: 9.5±1.9 s; NS) nor the HHb mean response time (normoxia: 20.6±2.8 s vs. hyperoxia: 19.6±2.3 s; NS). Likewise, Hbtot was not different between normoxia and hyperoxia. CONCLUSION: These results indicate that moderate hyperoxia has no effect on muscle deoxygenation kinetics at the onset of heavy exercise. It suggests that muscle (V)O2 increases at the same rate than O2 delivery when O2 availability is enhanced.

Spatial and temporal signalling by calcium.

Recent research has shown the importance of the spatial and temporal aspects of calcium signals, which depend upon regenerative properties of the inositol trisphosphate and ryanodine receptors that regulate the release of calcium from internal stores. Initiation sites have been found to spontaneously release calcium, recognized as 'hot spots' or 'sparks', and can trigger a wave that spreads through a process of calcium-induced calcium release.

The effect of a cold environment on physical activity profiles in elite soccer match-play.

In this study, the effect of cold temperature on the physical activity profiles of professional soccer players in official match-play was investigated. Computerised motion-analysis was used to analyse performance in 9 players (4 defenders and 5 midfielders) in 4 temperature ranges: ≤ 5°C (29 matches), 6-10°C (62 matches), 11-20°C (48 matches) and ≥ 21°C (27 matches). Performance was analysed per minute for total distance covered and distance run in 3 categories: 0.0-14.3 km/h (walking/low/moderate); 14.4-19.7 km/h (running); ≥ 19.8 km/h (high-intensity). Results showed that while total distance run per minute was unaffected in colder conditions, midfielders ran significantly shorter distances in warmer temperatures: ≥21°C = 118.7 ± 6.9 m vs. ≤ 5°C=124.2 ± 7.1 m, p < 0.01; 6-10°C = 123.6 ± 6.8 m, p < 0.01; and, 11-20°C = 123.4 ± 5.4, p < 0.05). The total distance covered at 3 intensities and across halves was unaffected by temperature. Similarly, high-intensity efforts across match halves and in the first and final 5-min periods in each half of normal time were unaffected by temperature. In contrast, high-intensity efforts in midfielders across 15-min intervals were affected by temperature with greater distances covered per minute in the 30-45 min period in matches played in temperatures ≤ 5°C vs. the corresponding period in those played in temperatures ≥ 21°C (9.1 ± 3.8 m vs. 6.2 ± 3.0 m, p < 0.05). The present findings generally suggest that physical performance in professional soccer does not decrease in cold temperatures.

Exercise-Based Strategies to Prevent Muscle Injury in Male Elite Footballers: An Expert-Led Delphi Survey of 21 Practitioners Belonging to 18 Teams from the Big-5 European Leagues.

PURPOSE: To define based on expert opinion and practical experience using a systematic and scientific approach, (1) the perceived most effective exercise-based strategies to prevent muscle injury in elite footballers; and, (2) when and how these exercise programs are prescribed based on the number of days between games i.e. implementation strategy. METHODS: A Delphi survey obtained opinions and assessed for agreement. Delphi respondents consisted of 21 experienced sports practitioners (12 ± 5.3 years in elite football and with an academic background) belonging to 18 teams from the Big-5 European football leagues; England, France, Germany, Italy, Spain. Three teams were represented collaboratively by two experts. The Delphi process involves sequential rounds each evolving based on the responses from the previous. The number of rounds is not pre-defined and continues until an agreement is either achieved or it is clear that no agreement will be reached. Frequency of responses was recorded where the agreement was sought (i.e. in closed questions) and an agreement was achieved if ≥ 13/18 (70%) respondents agreed. For open-ended questions, a qualitative content analysis was performed to identify recurring themes and when themes were specified by ≥ 13 (70%), these were also considered as reaching an agreement. Practitioners had the opportunity to raise concerns if they disagreed with the 'agreement from recurrent themes'. RESULTS: There were four Delphi rounds (100% response for each round). Sprinting and High-Speed Running (HSR) focused exercises were agreed as most effective (perceived) to prevent muscle injuries. Eccentric exercise was perceived as the next most effective. It was agreed that sprinting and HSR be integrated into coaches training, and target 100% of players worst-case match scenario (e.g. volume, intensity) based on individual maximum speeds. Eccentric exercise was recommended to be implemented according to the context of the main football session and planned/actual sprinting and HSR content. It was agreed that eccentrics can be performed before or after training, context dependent. The day to perform specific sprinting and HSR or eccentric exercises depended on the proximity of previous and upcoming matches. Other exercises reaching agreement as 'somewhat effective' included concentric and isometric, horizontal and vertical plyometrics, coordination, core and dynamic flexibility in addition to core stability. No agreement was reached for multi-joint, resisted sprinting, kicking or agility exercises nor simultaneous single-leg strength and stability. Finally, no agreement was reached regarding programming variables e.g. sets, repetitions as deemed too contextual. CONCLUSION: Regarding exercise-based strategies, particular importance agreed by the Delphi expert group was to focus on sprinting, HSR and eccentric exercises, integrated with a variety of other exercise modes which also carry some level of effectiveness in a multidimensional programme. Context was agreed to be key and decision-making about when to undertake/ how to prescribe exercise strategies to be made according to the content of normal football training and the proximity of matches.

In vivo administration of acepromazine or promethazine to horse decreases the reactive oxygen species production response of subsequently isolated neutrophils to stimulation with phorbol myristate acetate.

The previous experiments have shown that some phenothiazines have antioxidant and anti-inflammatory properties in vitro. In this study the inhibition of the production of reactive oxygen species (ROS) by neutrophils was studied in two groups of horses, which received a dose of 0.1 mg/kg of either acepromazine or promethazine intravenously. Blood samples were collected before (T0) and 0.5, 1, 3 and 5 h after drug administration. The chemiluminescence (CML) response of neutrophils was measured ex vivo in the presence of luminol for a period of 10 min and the maximum CML value (peak value) recorded. There was a significant inhibition of the ROS production in the acepromazine treated group (49% inhibition) at 5 h after administration and in the promethazine group (24% inhibition) at 3 h after administration (P < 0.05 vs. T0). These findings are of therapeutic relevance in the use of phenothiazines in equine patients with inflammatory diseases where neutrophil activation and ROS production are implicated.

[VEGF inhibitors in ophthalmology]. / Utilisation des anticorps anti-VEGF en ophtalmologie.

The exsudative form of age-related macular degeneration (AMD) is characterized by the development of choroidal neovascularization (CNV) under the retina driven in part by the vascular endothelial growth factor. Several VEGF inhibitors have recently been produced for ocular administration. This review will focus on ranibizumab which is a specific antibody neutralizing all VEGF isoforms. The development, pharmacokinetics, clinical efficacy, current and future indications of ranibizumab are discussed.

Direct stimulation of the oxidative activity of isolated equine neutrophils by TNF-alpha and IL-1beta.

The capacity of the two cytokines TNF-alpha and IL-1beta to directly stimulate the oxidative activity of polymorphonuclear neutrophils remains debated. The purpose of this study was to verify if a direct stimulation of equine neutrophils by TNF-alpha and IL-1beta was possible. Equine neutrophils were isolated from blood by discontinuous density gradient centrifugation. The cell viability after isolation was >98%. The neutrophils were used at 1.25 x 10(6) cells by assay, immediately after isolation. The oxidative activity of neutrophils was measured by luminol- or lucigenin-enhanced chemiluminescence (CL), and the CL was recorded for 60 min. TNF-alpha and IL-1beta were used at concentrations ranging from 0.001 to 100 ng (0.0017-167 ng ml(-1)) for 1.25 x 10(6) neutrophils, and added to the cells just before the CL measurement. Both cytokines highly stimulated the lucigenin-enhanced CL of equine neutrophils in a dose-dependent manner. TNF-alpha was already active at 0.001 ng and IL-1beta at 0.01 ng. The CL response obtained with TNF-alpha was maximal after 5 min and more pronounced with luminol than with lucigenin. With IL-1beta, the luminol-enhanced CL response of neutrophils was short-lived and inversely proportional to the cytokine concentration: the CL response returned to baseline after 12 min, and became even lower than the baseline value for 10 and 100 ng IL-1beta. As luminol (but not lucigenin) enters the cell, we hypothesized that a rapid intracellular consumption of the luminol molecules occurred, explaining the rapid and intense CL response. The choice of the CL enhancer used in previous CL studies of neutrophils stimulation by cytokines could perhaps explain that controversial results were reported. In conclusion, we demonstrated a direct activation of the oxidative activity of equine neutrophils by TNF-alpha and IL-1beta, which was dose-dependent and obtained with very low doses equivalent to the plasma concentrations measured for both cytokines in equine septic shock. TNF-alpha and IL-1beta can thus aggravate neutrophils oxidative activity during septic shock in horses.

Inhibitory effect of curcuminoids and tetrahydrocurcuminoids on equine activated neutrophils and myeloperoxidase activity.

In the horse, the inflammation response to various pathologies (intestinal strangulations, laminitis, etc.) involves an excessive stimulation of the polymorphonuclear neutrophils releasing reactive oxygen species (ROS) and myeloperoxidase (MPO). The aim of the present work was to study the effect of natural polyphenols, curcuminoids and tetrahydrocurcuminoids (THC) on isolated stimulated equine neutrophils and on the activity of purified MPO. The ROS production and the release of MPO by activated neutrophils were measured by chemiluminescence and ELISA techniques, respectively. The activity of purified MPO was measured by studying its nitration, chlorination or oxidation capacity and by using an original method called SIEFED allowing the study of drug interaction with the enzyme without interferences of the medium. Curcuminoids and THC had dose-dependent inhibitory effects on ROS production and MPO release by activated neutrophils and on purified MPO activity. We suggest that the higher efficacy of curcuminoids versus THC could be explained, at least partially, by its chemical structure: the conjugated double bounds and the plane structure of curcuminoids made easier the neutralization of the radical species generated by activated neutrophils and the interaction of the drug with the active site of MPO. These inhibitory effects of curcuminoids on the oxidant activity of equine neutrophils and on MPO activity open therapeutic perspectives in equine pathologies with excessive inflammatory reactions.

Effects of unfractionated and fractionated heparins on myeloperoxidase activity and interactions with endothelial cells: possible effects on the pathophysiology of equine laminitis.

As heparins are sometimes used to prevent equine laminitis, the interactions between equine neutrophil myeloperoxidase (MPO), unfractionated (UFH) and fractionated low molecular weight (LMWH) heparins and digital endothelium have been investigated. The effects of the heparins on purified equine MPO activity were tested by immunocapture followed by enzymatic detection. Endothelium-MPO interactions were assessed by measuring total and active MPO uptake by arterial and venous digital endothelial cells in culture with or without the addition of heparins. A dose-dependent MPO inhibition by UFH and LMWH was seen, with the greatest reduction in MPO activity noted with the highest concentration of LMWH. The MPO capture was greater in arterial cells, but heparins better inhibited MPO capture in venous cells. The activity of cell-bound MPO was almost completely suppressed by the heparins, and no differences were observed between UFH and LMWH. The results confirm the anti-inflammatory properties of heparins and allow a better understanding of the potential role of MPO in laminitis.