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1.
Rev Neurol (Paris) ; 179(9): 961-966, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37328356

RESUMO

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.


Assuntos
Doença de Parkinson , Transtornos Parkinsonianos , Humanos , Doença de Parkinson/diagnóstico , Doença de Parkinson/metabolismo , Estudos Prospectivos , Estudos Transversais , Metabolismo dos Lipídeos , Transtornos Parkinsonianos/diagnóstico , Biomarcadores , Estresse Oxidativo
2.
Phys Rev Lett ; 122(8): 088101, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30932600

RESUMO

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.

3.
Rev Neurol (Paris) ; 175(10): 686-692, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31130312

RESUMO

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.


Assuntos
Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/psicologia , Bases de Dados Factuais , Humanos , Ataque Isquêmico Transitório/epidemiologia , Ataque Isquêmico Transitório/etiologia , Ataque Isquêmico Transitório/psicologia , Psicologia , Saúde Pública/tendências , Fatores de Risco , Fatores Socioeconômicos
4.
Br J Anaesth ; 118(3): 372-379, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28203726

RESUMO

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.


Assuntos
Procedimentos Cirúrgicos Eletivos , Tratamento de Emergência , Conteúdo Gastrointestinal/diagnóstico por imagem , Cuidados Pré-Operatórios/métodos , Antro Pilórico/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos
5.
Anaesthesia ; 72(9): 1112-1116, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28695978

RESUMO

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.


Assuntos
Aspiração Respiratória de Conteúdos Gástricos/diagnóstico por imagem , Aspiração Respiratória de Conteúdos Gástricos/prevenção & controle , Estômago/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anatomia Transversal , Índice de Massa Corporal , Estudos de Coortes , Estudos Transversais , Serviços Médicos de Emergência , Jejum , Feminino , Esvaziamento Gástrico , Humanos , Masculino , Pessoa de Meia-Idade , Morfina/farmacologia , Antro Pilórico/diagnóstico por imagem , Reprodutibilidade dos Testes , Ultrassonografia , Adulto Jovem
6.
Rev Med Liege ; 71(2): 90-3, 2016 Feb.
Artigo em Francês | MEDLINE | ID: mdl-27141652

RESUMO

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.


Assuntos
Glaucoma de Ângulo Aberto/cirurgia , Stents , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos
7.
Int J Sports Med ; 34(6): 554-8, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23258607

RESUMO

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.


Assuntos
Desempenho Atlético/fisiologia , Teste de Esforço/métodos , Corrida/fisiologia , Futebol/fisiologia , Adolescente , Creatina Quinase/fisiologia , Fadiga/metabolismo , Humanos , Contração Isométrica/fisiologia , Fatores de Tempo , Ácido Úrico/metabolismo , Adulto Jovem
8.
Folia Morphol (Warsz) ; 82(3): 568-579, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35692114

RESUMO

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.


Assuntos
Nervo Facial , Artérias Meníngeas , Base do Crânio , Artérias Meníngeas/anatomia & histologia , Artérias Meníngeas/cirurgia , Base do Crânio/irrigação sanguínea , Humanos , Cadáver , Nervo Facial/irrigação sanguínea , Nervo Facial/cirurgia , Procedimentos Endovasculares
9.
Int J Sports Med ; 33(1): 36-42, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22012641

RESUMO

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.


Assuntos
Traumatismos em Atletas/etiologia , Desempenho Atlético/fisiologia , Futebol/fisiologia , Traumatismos em Atletas/epidemiologia , Humanos , Processamento de Imagem Assistida por Computador , Incidência , Escala de Gravidade do Ferimento , Estudos Prospectivos , Corrida/fisiologia , Estudos de Tempo e Movimento
10.
J Sports Med Phys Fitness ; 52(2): 137-43, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22525648

RESUMO

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.


Assuntos
Hiperóxia/metabolismo , Oxigênio/metabolismo , Esforço Físico , Músculo Quadríceps/metabolismo , Adulto , Hemoglobinas/metabolismo , Humanos , Masculino , Oxigênio/farmacocinética , Consumo de Oxigênio , Adulto Jovem
11.
Curr Opin Cell Biol ; 6(2): 267-74, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7517689

RESUMO

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.


Assuntos
Cálcio/metabolismo , Transdução de Sinais , Animais , Membrana Celular/metabolismo , Citosol/metabolismo , Humanos , Canais Iônicos/fisiologia , Modelos Biológicos , Receptores de Superfície Celular/fisiologia , Fatores de Tempo
12.
Int J Sports Med ; 32(7): 542-5, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21563033

RESUMO

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.


Assuntos
Temperatura Baixa , Corrida/fisiologia , Futebol/fisiologia , Desempenho Atlético/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Estudos de Tempo e Movimento
13.
Sports Med ; 50(9): 1667-1681, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32676903

RESUMO

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.


Assuntos
Traumatismos em Atletas/prevenção & controle , Músculo Esquelético/lesões , Condicionamento Físico Humano/métodos , Futebol/lesões , Atletas , Europa (Continente) , Humanos , Masculino , Inquéritos e Questionários
14.
J Vet Pharmacol Ther ; 32(6): 541-7, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20444008

RESUMO

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.


Assuntos
Acepromazina/farmacologia , Cavalos , Neutrófilos/efeitos dos fármacos , Prometazina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Acepromazina/administração & dosagem , Animais , Antioxidantes/farmacologia , Células Cultivadas , Antagonistas de Dopamina/farmacologia , Neutrófilos/metabolismo , Prometazina/administração & dosagem
15.
Rev Med Liege ; 64(5-6): 323-6, 2009.
Artigo em Francês | MEDLINE | ID: mdl-19642468

RESUMO

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.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Aptâmeros de Nucleotídeos/uso terapêutico , Degeneração Macular/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Bevacizumab , Humanos , Ranibizumab , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
16.
Vet Immunol Immunopathol ; 121(1-2): 101-6, 2008 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-18006077

RESUMO

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.


Assuntos
Cavalos/sangue , Interleucina-1beta/farmacologia , Neutrófilos/efeitos dos fármacos , Explosão Respiratória/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Acridinas/química , Animais , Medições Luminescentes , Luminol/química , Ativação de Neutrófilo/efeitos dos fármacos , Ativação de Neutrófilo/imunologia , Neutrófilos/imunologia , Explosão Respiratória/imunologia
17.
Physiol Res ; 57(4): 577-587, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-17705665

RESUMO

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.


Assuntos
Curcumina/análogos & derivados , Curcumina/farmacologia , Cavalos/fisiologia , Ativação de Neutrófilo/efeitos dos fármacos , Peroxidase/metabolismo , Animais , Benzotiazóis/metabolismo , Separação Celular , Sobrevivência Celular/efeitos dos fármacos , Cloretos/metabolismo , Flavonoides/química , Flavonoides/farmacologia , Imuno-Histoquímica , Técnicas In Vitro , Luminescência , Nitratos/metabolismo , Oxirredução , Fenóis/química , Fenóis/farmacologia , Polifenóis , Espécies Reativas de Oxigênio/metabolismo , Ácidos Sulfônicos/metabolismo , Taurina/metabolismo , Tirosina/farmacologia
18.
Vet J ; 178(1): 62-9, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17942351

RESUMO

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.


Assuntos
Células Endoteliais/efeitos dos fármacos , Doenças do Pé/veterinária , Heparina de Baixo Peso Molecular/farmacologia , Heparina/farmacologia , Doenças dos Cavalos/fisiopatologia , Peroxidase/metabolismo , Animais , Células Cultivadas , Células Endoteliais/metabolismo , Doenças do Pé/fisiopatologia , Cavalos
19.
J Clin Invest ; 89(1): 197-202, 1992 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1370294

RESUMO

The central importance of xanthine dehydrogenase (XDH) and xanthine oxidase (XO) in the pathobiochemistry of a number of clinical disorders underscores the need for a comprehensive understanding of the regulation of their expression. This study was undertaken to examine the effects of cytokines on XDH/XO activity and gene expression in pulmonary endothelial cells. The results indicate that IFN-gamma is a potent inducer of XDH/XO activity in rat lung endothelial cells derived from both the microvasculature (LMVC) and the pulmonary artery. In contrast, interferon-alpha/beta, tumor necrosis factor-alpha, interleukin-1 or -6, lipopolysaccharide and phorbol myristate acetate have no demonstrable effect. The increase in XDH/XO activity requires new protein synthesis. By Northern analysis, IFN-gamma markedly increases the level of the 5.0-kb XDH/XO mRNA in LMVC. The increase is due, in part, to increased transcription rate of the XDH/XO gene. Transcriptional activation does not require new protein synthesis. The physiologic relevance of these observations was evaluated by administering IFN-gamma to rats. Intraperitoneal administration leads to an increased XDH/XO activity and XDH/XO mRNA level in rat lungs. In sum, IFN-gamma is a potent and biologically relevant inducer of XDH/XO expression; the major site of upregulation occurs at the transcriptional level.


Assuntos
Endotélio Vascular/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Pulmão/metabolismo , Xantina Desidrogenase/genética , Xantina Oxidase/genética , Animais , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Cicloeximida/farmacologia , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Inflamação/metabolismo , Interferons/farmacologia , Pulmão/efeitos dos fármacos , Hibridização de Ácido Nucleico , Biossíntese de Proteínas , RNA Mensageiro/análise , Ratos , Transcrição Gênica , Fator de Necrose Tumoral alfa/farmacologia
20.
Res Vet Sci ; 82(1): 68-75, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16780906

RESUMO

Markers of cartilage breakdown enable studying the degradation of cartilage matrix in equine joint pathologies. This study was designed to determine the levels of Coll2-1, a peptide of the triple helix of type II collagen, and Coll2-1NO(2), its nitrated form in the plasma of healthy horses (controls; n=37) and horses suffering from osteochondrosis (n=34). Clinical and arthroscopic scores were attributed reflecting the severity of lesions and were related to the plasma levels of Coll2-1 and Coll2-1NO(2). The median of Coll2-1 was significantly higher in the control group, whereas the mean of Coll2-1NO(2) showed significant elevation in the pathological group. However, the measurement means of scoring classes did not vary significantly. The markers were able to differentiate the group of horses suffering from osteochondrosis from the group of healthy horses. The elevation of Coll2-1NO(2) in the pathological group indicates an inflammation, mediated through reactive oxygen species and/or increased myeloperoxidase activity.


Assuntos
Doenças das Cartilagens/veterinária , Colágeno Tipo II/metabolismo , Doenças dos Cavalos/diagnóstico , Doenças dos Cavalos/metabolismo , Nitrocompostos/metabolismo , Animais , Biomarcadores/análise , Doenças das Cartilagens/diagnóstico , Doenças das Cartilagens/metabolismo , Doenças das Cartilagens/patologia , Colágeno Tipo II/química , Feminino , Doenças dos Cavalos/patologia , Cavalos , Inflamação/diagnóstico , Inflamação/metabolismo , Inflamação/veterinária , Masculino
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