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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.
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Plaquetas , Diferenciação Celular , Imunomodulação , Células-Tronco Mesenquimais , Animais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/imunologia , Cavalos , Plaquetas/metabolismo , Proliferação de Células/efeitos dos fármacos , Técnicas de Cultura de Células/métodos , Células Cultivadas , Músculos , ImunofenotipagemRESUMO
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.
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Antivirais , Transtornos Mentais , Humanos , Masculino , Estudos Transversais , Feminino , Antivirais/uso terapêutico , Pessoa de Meia-Idade , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia , Adulto , Bélgica/epidemiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/psicologia , Resultado do Tratamento , Hepatite C/epidemiologia , Hepatite C/complicações , Hospitais Psiquiátricos , Resposta Viral SustentadaRESUMO
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.
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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 OxidativoRESUMO
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.
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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 EndovascularesRESUMO
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.
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Traumatismos em Atletas/prevenção & controle , Músculo Esquelético/lesões , Condicionamento Físico Humano/métodos , Futebol/lesões , Atletas , Europa (Continente) , Humanos , Masculino , Inquéritos e QuestionáriosRESUMO
Abstract Pancreatic alpha and beta cells release the main hormones involved in blood glucose regulation: glucagon and insulin, respectively. Based on the observation that metabolic oscillations are related to electrical activity and, in turn, to insulin secretion in beta cells, in the present work we use a mathematical modelling approach to explore the contribution of glycolytic oscillations to electrical activity in alpha cells. Due to lack of data about metabolism in alpha cells and taking into account that pancreatic cells comes from a common progenitor, we used a previous model of pancreatic beta cells and focus on the main differences between both cell types. The main finding contrasts with beta cells since electrical activity in alpha cells could be triggered independently of glycolic oscillations. It suggests that alpha cells are stimulated by blood glucose through a different pathway, which is in agreement with the role of alpha cells during hypoglycemia.
Resumen Las células alfa y beta de páncreas secretan las dos hormonas más importantes para la regulación de la glucosa en sangre: el glucagón y la insulina, respectivamente. Dado que en células beta se ha observado la presencia de oscilaciones metabólicas relacionadas con su actividad eléctrica y, por tanto, con la secreción de insulina, en este trabajo se presenta un estudio de la posible relación entre las oscilaciones glicolíticas y la actividad eléctrica en células alfa mediante un enfoque de modelación matemática. Debido a la falta de información sobre el metabolismo en las células alfa y tomando en cuenta que las células pancreáticas provienen de un progenitor común, se utilizó un modelo previamente propuesto de células beta y se tomaron en cuenta las principales diferencias entre ambos tipos celulares para el análisis. Nuestros resultados muestran que, a diferencia de las células beta, la actividad eléctrica en células alfa puede dispararse independientemente de la presencia de oscilaciones glicolíticas, lo cual sugiere que estas células son estimuladas por la glucosa a través de una ruta metabólica diferente a la propuesta para células beta, lo cual es congruente con su papel regulador durante periodos de baja glucosa.
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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.
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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 SocioeconômicosRESUMO
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.
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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.
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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 JovemRESUMO
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.
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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 ProspectivosRESUMO
BACKGROUND: Neck pain (NP) is disabling and costly. OBJECTIVES: To assess the effectiveness of exercise on pain, disability, function, patient satisfaction, quality of life (QoL) and global perceived effect (GPE) in adults with NP. METHODS: We searched computerised databases up to May 2014 for randomized controlled trials (RCTs) comparing exercise to a control in adults with NP with/without cervicogenic headache (CGH) or radiculopathy. Two reviewers independently conducted selection, data abstraction and assessed risk of bias. Meta-analyses were performed to establish pooled standardised mean differences (SMDp). The Grade of Recommendation, Assessment, Development and Evaluation (GRADE) was used to summarise the body of evidence. MAIN RESULTS: The following exercises (27 trials) were supported by 'Moderate GRADE' evidence: For chronic NP, 1) cervico-scapulothoracic and upper extremity (UE) strengthening for moderate to large pain reduction immediately post treatment (IP) and at short-term (ST) follow-up; 2) scapulothoracic and UE endurance training for a small pain reduction (IP/ST); 3) cervical, shoulder and scapulothoracic strengthening and stretching exercise for a small to large pain reduction in the long-term (LT) (SMDp -0.45 [95%CI: -0.72 to -0.18]) and function improvement; 4) cervico-scapulothoracic strengthening/stabilisation exercises for pain and function at intermediate-term (IT) (SMDp -14.90 [95%CI: -22.40 to -7.39]). 5) mindfulness exercises (Qigong) for minor improved function but not GPE (ST). For chronic CGH, cervico-scapulothoracic strengthening and endurance exercises including pressure biofeedback for small/moderate improvement of pain, function and GPE (IP/LT). AUTHORS' CONCLUSIONS: Specific strengthening exercises of the neck, scapulothoracic and shoulder for chronic NP and chronic CGH are beneficial. Future research should explore optimal dosage.
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Dor Crônica/terapia , Terapia por Exercício , Cervicalgia/terapia , Traumatismos em Chicotada/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Dor Crônica/fisiopatologia , Humanos , Pessoa de Meia-Idade , Cervicalgia/fisiopatologia , Modalidades de Fisioterapia , Qualidade de Vida , Traumatismos em Chicotada/fisiopatologiaRESUMO
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.
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Glaucoma de Ângulo Aberto/cirurgia , Stents , Humanos , Procedimentos Cirúrgicos Minimamente InvasivosRESUMO
Myeloperoxidase (MPO) is a pro-oxidant enzyme involved in inflammation, and the measurement of its activity in biological samples has emerged essential for laboratory and clinical investigations. We will describe a new method which combines the SIEFED (specific immunological extraction followed by enzymatic detection) and ELISA (ELISAcb) techniques to measure the active and total amounts of MPO on the same human sample and with the same calibration curve, as well as to define an accurate ratio between both the active and total forms of the enzyme. The SIEFED/ELISAcb method consists of the MPO extraction from aqueous or biological samples by immobilized anti-MPO antibodies coated onto microplate wells. After a washing step to eliminate unbound material, the activity of MPO is measured in situ by adding a reaction solution (SIEFED). Following aspiration of the reaction solution, a secondary anti-MPO antibody is added into the wells and the ELISAcb test is carried out in order to measure the total MPO content. To validate the combined method, a comparison was made with SIEFED and ELISA experiments performed separately on plasma samples isolated from human whole blood, after a neutrophil stimulation. The SIEFED/ELISAcb provides a suitable tool for the measurement of specific MPO activity in biological fluids and for the estimation of the inhibitory potential of a fluid. The method can also be used as a pharmacological tool to make the distinction between a catalytic inhibitor, which binds to MPO and inhibits its activity, and a steric inhibitor, which hinders the enzyme and prevents its immunodetection.
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Ensaios Enzimáticos/métodos , Inibidores Enzimáticos/farmacologia , Ensaio de Imunoadsorção Enzimática/métodos , Peroxidase/metabolismo , Animais , Anticorpos Imobilizados , Inibidores Enzimáticos/sangue , Cavalos , Humanos , Neutrófilos/enzimologia , Peroxidase/sangue , Peroxidase/imunologiaRESUMO
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.
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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 JovemRESUMO
Rhythms abound in biological systems, particularly at the cellular level where they originate from the feedback loops present in regulatory networks. Cellular rhythms can be investigated both by experimental and modeling approaches, and thus represent a prototypic field of research for systems biology. They have also become a major topic in synthetic biology. We review advances in the study of cellular rhythms of biochemical rather than electrical origin by considering a variety of oscillatory processes such as Ca++ oscillations, circadian rhythms, the segmentation clock, oscillations in p53 and NF-κB, synthetic oscillators, and the oscillatory dynamics of cyclin-dependent kinases driving the cell cycle. Finally we discuss the coupling between cellular rhythms and their robustness with respect to molecular noise.
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Periodicidade , Biologia de Sistemas , Animais , Ciclo Celular , AMP Cíclico/metabolismo , Dictyostelium/metabolismo , Dictyostelium/fisiologiaRESUMO
Analysis of the mechanisms underlying the inflammatory response in amoebiasis is important to understand the immunopathology of the disease. Mucosal associated effector and regulatory T cells may play a role in regulating the inflammatory immune response associated to Entamoeba histolytica infection in the colon. A subpopulation of regulatory T cells has recently been identified and is characterized by the expression of the chemokine receptor CCR9. In this report, we used CCR9 deficient (CCR9(-/-)) mice to investigate the role of the CCR9(+) T cells in a murine model of E. histolytica intestinal infection. Intracecal infection of CCR9(+/+), CCR9(+/-) and CCR9(-/-) mice with E. histolytica trophozoites, revealed striking differences in the development and nature of the intestinal inflammatory response observed between these strains. While CCR9(+/+) and CCR9(+/-) mice were resistant to the infection and resolved the pathogen-induced inflammatory response, CCR9(-/-) mice developed a chronic inflammatory response, which was associated with over-expression of the cytokines IFN-γ, TNF-α, IL-4, IL-6 and IL-17, while IL-10 was not present. In addition, increased levels of CCL11, CCL20 and CCL28 chemokines were detected by qRT-PCR in CCR9(-/-) mice. E. histolytica trophozoites were identified in the lumen of the cecum of CCR9(-/-) mice at seven days post infection (pi), whereas in CCR9(+/+) mice trophozoites disappeared by day 1 pi. Interestingly, the inflammation observed in CCR9(-/-) mice, was associated with a delayed recruitment of CD4(+)CD25(+)FoxP3(+) T cells to the cecal epithelium and lamina propria, suggesting that this population may play a role in the early regulation of the inflammatory response against E. histolytica, likely through IL-10 production. In support of these data, CCR9(+) T cells were also identified in colon tissue sections obtained from patients with amoebic colitis. Our data suggest that a population of CCR9(+)CD4(+)CD25(+)FoxP3(+) T cells may participate in the control and resolution of the inflammatory immune response to E. histolytica infection.
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Modelos Animais de Doenças , Disenteria Amebiana/imunologia , Entamoeba histolytica/imunologia , Receptores CCR/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Quimiocina CCL11/genética , Quimiocina CCL11/imunologia , Quimiocina CCL11/metabolismo , Quimiocina CCL20/genética , Quimiocina CCL20/imunologia , Quimiocina CCL20/metabolismo , Quimiocinas CC/genética , Quimiocinas CC/imunologia , Quimiocinas CC/metabolismo , Disenteria Amebiana/metabolismo , Disenteria Amebiana/parasitologia , Entamoeba histolytica/fisiologia , Citometria de Fluxo , Fatores de Transcrição Forkhead/imunologia , Fatores de Transcrição Forkhead/metabolismo , Expressão Gênica , Humanos , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Interferon gama/imunologia , Interferon gama/metabolismo , Interleucina-17/imunologia , Interleucina-17/metabolismo , Subunidade alfa de Receptor de Interleucina-2/imunologia , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Interleucina-4/imunologia , Interleucina-4/metabolismo , Interleucina-6/imunologia , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores CCR/genética , Receptores CCR/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Trofozoítos/imunologia , Trofozoítos/fisiologia , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
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 JovemRESUMO
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 MovimentoRESUMO
The purpose of this study was to explore the potential modulation of equine neutrophil oxidative burst by a series of classical NSAIDs which was subsequently monitored by the luminol or lucigenin-enhanced chemiluminescence (CL) technique. A significant dose-dependent inhibition of the luminol CL was observed with the majority of investigated drugs. This inhibition was very significant for phenylbutazone and Indomethacin; while for aspirin, a higher concentration is required. The action of Ketoprofen was significant during the first 5 min and only when the concentration was above 1 mM. Indomethacin and acetylsalicylic acid result in an inhibition dose-dependent of luminol CL. On the other hand, the phenylbutazone showed an inhibiting effect when used either luminol or lucigenin though luminol is slightly better. When the ketoprofen is considered, an inhibiting effect of luminal CL was observed but less significant than the other NSAIDs investigated. The flunixin meglumine enhances strongly the CL.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Cavalos/imunologia , Neutrófilos/efeitos dos fármacos , Acridinas/química , Animais , Relação Dose-Resposta a Droga , Medições Luminescentes/veterinária , Luminol/química , Neutrófilos/metabolismo , Oxirredução , Explosão Respiratória/efeitos dos fármacosRESUMO
In hepatocytes, as in other cell types, Ca(2+) signaling is subject to complex regulations, which result largely from the intrinsic characteristics of the different inositol 1,4,5-trisphosphate receptor (InsP(3)R) isoforms and from their interactions with other proteins. Although sigma1 receptors (Sig-1Rs) are widely expressed in the liver, their involvement in hepatic Ca(2+) signaling remains unknown. We here report that in this cell type Sig-1R interact with type 1 isoforms of the InsP(3) receptors (InsP(3)R-1). These results obtained by immunoprecipitation experiments are confirmed by the observation that Sig-1R proteins and InsP(3)R-1 colocalize in hepatocytes. However, Sig-1R ligands have no effect on InsP(3)-induced Ca(2+) release in hepatocytes. This can be explained by the rather low expression level expression of InsP(3)R-1. In contrast, we find that Sig-1R ligands can inhibit agonist-induced Ca(2+) signaling via an inhibitory effect on InsP(3) synthesis. We show that this inhibition is due to the stimulation of PKC activity by Sig-1R, resulting in the well-known down-regulation of the signaling pathway responsible for the transduction of the extracellular stimulus into InsP(3) synthesis. The PKC sensitive to Sig-1R activity belongs to the family of conventional PKC, but the precise molecular mechanism of this regulation remains to be elucidated.