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1.
Rech Soins Infirm ; 151(4): 60-74, 2023.
Artigo em Francês | MEDLINE | ID: mdl-37015858

RESUMO

Introduction: The number of elderly patients admitted to emergency departments (EDs) continues to rise each year. However, due to time and structural constraints, these facilities do not allow for optimal identification of patients at risk of rehospitalization and loss of independence. Objective: To identify the characteristics of patients over the age of 75 discharged from the ED without indications for hospitalization, and to illustrate the importance of advanced practice nurses (APN) in identifying predictive factors of loss of independence. Method: A prospective, single-center, observational pilot study of a cohort of 67 patients in an emergency department. Results: The study allowed the researchers to characterize a female, aging, and vulnerable patient population. Re-evaluation at the six-month mark revealed a functional decline in 23% of patients. Relevant predictive autonomy loss factors including recent cognitive decline, hearing impairment, and weight loss are put forward for future research. Discussion: These results, in line with the findings of previous studies, highlight the potential added value of APNs in indentifying the functional decline within this patient population. Conclusion: Given the diverse, complex, and fragile health condition of elderly patients when discharged from the emergency department, APNs play a key role in improving care and preventing loss of independence within this patient population.


Introduction: Un nombre croissant de personnes âgées sont admises aux urgences chaque année, mais les contraintes temporelles et structurelles de ces services ne permettent pas de repérer de façon optimale les personnes à risque de réhospitalisation et de perte d'autonomie. Objectif: Décrire la population des personnes de plus de 75 ans sortant des urgences sans indication d'hospitalisation, montrer la contribution d'une infirmière en pratique avancée (IPA) en regard des facteurs prédictifs de perte d'autonomie identifiés. Méthode: Étude pilote, prospective, monocentrique, descriptive d'une cohorte de 67 patients, menée aux urgences. Résultats: L'étude a permis de décrire une population féminine, vieillissante et fragile. La réévaluation à six mois a permis d'observer un déclin fonctionnel pour 23 % des patients. Des facteurs prédictifs de perte d'autonomie, pour cette population d'étude, sont proposés. Discussion: Ces résultats, cohérents avec ceux de la littérature, montrent la plus-value que pourrait avoir l'IPA en regard du déclin fonctionnel de cette population. Conclusion: La population âgée des urgences rentrant au domicile étant hétérogène, complexe et fragile, l'intervention d'une IPA a été mise en place pour améliorer la prise en soins des personnes et prévenir leur perte d'autonomie.


Assuntos
Hospitalização , Readmissão do Paciente , Humanos , Feminino , Idoso , Projetos Piloto , Estudos Prospectivos , Serviço Hospitalar de Emergência
2.
Clin Linguist Phon ; 32(2): 166-179, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28837363

RESUMO

The aim of this study was to establish normative data on the speech disfluencies of normally fluent French-speaking children at age 4, an age at which stuttering has begun in 95% of children who stutter (Yairi & Ambrose, 2013). Fifty monolingual French-speaking children who do not stutter participated in the study. Analyses of a conversational speech sample comprising 250-550 words revealed an average of 10% total disfluencies, 2% stuttering-like disfluencies and around 8% non-stuttered disfluencies. Possible explanations for these high speech disfluency frequencies are discussed, including explanations linked to French in particular. The results shed light on the importance of normative data specific to each language.


Assuntos
Medida da Produção da Fala , Fala/fisiologia , Gagueira/diagnóstico , Pré-Escolar , Feminino , França , Voluntários Saudáveis , Humanos , Masculino , Gagueira/epidemiologia , Comportamento Verbal
3.
Clin Linguist Phon ; 29(8-10): 719-35, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25803317

RESUMO

This study aimed at directly assessing the hypothesis that attentional allocation capacity influences poor nonword repetition (NWR) performances in children with specific language impairment (SLI), using an attention demanding visual search task given concurrently with the NWR task. Twenty-one children with SLI, 21 typically developing children matched on age and 21 typically developing children matched on nonword span performed an immediate serial recall task of nonwords. The nonword lists were presented either alone or concurrently with the visual search task. Overall, results revealed a resource-sharing trade-off between the two tasks. Children with SLI were affected to the same extent as their span-matched controls by the necessity to allocate their attentional resources between the two tasks. Interestingly, nonword processing strategies seemed to differ among groups: age-matched controls allocated a larger part of their attentional resources to the encoding stage, whereas nonword recall was more attention demanding in children with SLI and younger controls.


Assuntos
Atenção , Comportamento Imitativo , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Testes de Linguagem , Terapia da Linguagem , Fonética , Semântica , Medida da Produção da Fala , Aprendizagem Verbal , Criança , Feminino , Humanos , Idioma , Transtornos do Desenvolvimento da Linguagem/terapia , Masculino , Memória de Curto Prazo , Reconhecimento Visual de Modelos , Valores de Referência , Vocabulário
4.
Clin Linguist Phon ; 29(8-10): 701-18, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25774764

RESUMO

The usage-based theory considers that the morphosyntactic productions of children with SLI are particularly dependent on input frequency. When producing complex syntax, the language of these children is, therefore, predicted to have a lower variability and to contain fewer infrequent morphosyntactic markers than that of younger children matched on morphosyntactic abilities. Using a spontaneous language task, the current study compared the complexity of the morphological and structural productions of 20 children with SLI and 20 language-matched peers (matched on both morphosyntactic comprehension and mean length of utterance). As expected, results showed that although basic structures were produced in the same way in both groups, several complex forms (i.e. tenses such as Imperfect, Future or Conditional and Conjunctions) were less frequent in the productions of children with SLI. Finally, we attempted to highlight complex linguistic forms that could be good clinical markers for these children.


Assuntos
Transtornos do Desenvolvimento da Linguagem/diagnóstico , Terapia da Linguagem/métodos , Idioma , Linguística , Medida da Produção da Fala , Bélgica , Criança , Pré-Escolar , Feminino , Humanos , Transtornos do Desenvolvimento da Linguagem/terapia , Masculino , Fonética , Semântica
5.
PLoS One ; 19(7): e0304212, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38990808

RESUMO

Stuttering is a speech disorder in which the flow of speech is disrupted by involuntary repetitions of sounds, syllables, words or phrases, stretched sounds or silent pauses in which the person is unable to produce sounds and sound transitions. Treatment success is the highest if stuttering is treated before the age of 6 years, before it develops into "persistent" stuttering. Stuttering treatment programs that focus directly on the speech of the child, like the Lidcombe Program, have shown to be effective in this age group. Mini-KIDS is also a treatment that focuses directly on the speech of the child. It is possible that capturing the increased brain plasticity at this age in combination with creating optimal conditions for recovery underlie these treatments' success rate. A treatment focusing on the cognitions, emotions and behaviour of the child, the social cognitive behaviour treatment (SCBT), is also frequently delivered in Belgium. In this study we want to compare, and collect data on the effectiveness, of these three treatment programs: Mini-KIDS, SCBT and the Lidcombe Program (protocol registered under number NCT05185726). 249 children will be allocated to one of three treatment groups. Stuttering specialists will treat the child (and guide the parents) with Mini-KIDS, the SCBT or the Lidcombe Program. They will be trained to deliver the programs meticulously. At 18 months after randomisation, the speech fluency of the child and the attitude of the child and parent(s) towards speech will be measured. It is expected that the three programs will achieve the same (near) zero levels of stuttering in nearly all children and a positive attitude towards speech at 18 months after the start of treatment. The amount of treatment hours to reach the (near) zero levels of stuttering will be compared between the different programmes. For families as well as for the health system this could generate important information.


Assuntos
Terapia Cognitivo-Comportamental , Fonoterapia , Gagueira , Gagueira/terapia , Gagueira/psicologia , Humanos , Pré-Escolar , Masculino , Fonoterapia/métodos , Feminino , Terapia Cognitivo-Comportamental/métodos , Resultado do Tratamento , Criança
6.
J Voice ; 2023 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-37487795

RESUMO

OBJECTIVES: Public speaking (PS) is frequently necessary in many professional, educational, and personal settings. Mastering this communication skill is particularly important in today's society. Training techniques for PS have been described in the literature. Given that PS anxiety affects performance, especially voice characteristics and speech fluency, the purpose of this scoping review is to examine, map, and narratively summarize the available evidence on PS interventions that target or affect voice or speech. METHODS: An extensive literature search was conducted in three bibliographic databases: Medline ALL/Ovid, PsycINFO/Ovid, and Eric/Ovid. Of the 850 studies identified, 22 met the eligibility criteria, and one was added from the reference lists of the included studies. RESULTS: A total of 23 studies were included. The interventions identified aim to improve speaking skills either by explicitly targeting the voice or speech (direct intervention, n = 15) or by targeting the cognitive, behavioral, psychological, or physical environment impacting the speaker's production (indirect intervention, n = 8). CONCLUSIONS: This scoping review provides the first published methodological summary of the characteristics of existing PS interventions that target or affect voice and speech. Heterogeneous characteristics were observed. Further studies are needed to determine which interventions are most effective.

7.
Nurs Open ; 10(3): 1437-1448, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36168185

RESUMO

OBJECTIVES: To examine the characteristics of the first Advanced Practice Nurses in France and to compare the French model to international standards. BACKGROUND: Common barriers and facilitators to their integration in healthcare provision have been identified internationally. In France, the legislative framework was introduced in 2016, and the first graduates entered the workforce in 2019. METHODS: The French model was examined in comparison with Hamric's conceptual framework and to the International Council of Nurses' guidelines and definitions. A cross-sectional survey was also conducted, using three self-administered online questionnaires. Two were distributed to 2019 and 2020 graduates and a third to the accredited programme directors. The characteristics of advanced practice nursing graduates were described and compared based on employment status and field of practice (primary vs secondary/tertiary care). RESULTS: Although the French model of advanced practice nursing meets Hamric's primary criteria and core competencies, it does not differentiate between Nurse Practitioner and Clinical Nurse Specialist roles. Of the 320 students enrolled in one of the 11 accredited training programmes 165 participated in the survey. Mean age was 40, and mean prior nursing experience was 15 years. By February 2021, 30% of respondents were still employed as Registered Nurses. Barriers to practice included insufficient income generation (primary care), the lack of position creation (secondary/tertiary care), the physician-dependent patient referral process and delays in prescription credentials approval. CONCLUSIONS: The implementation of advanced practice nursing in France faces several barriers. Legislative adjustments and greater financial incentives to practice seem warranted. RELEVANCE TO CLINICAL PRACTICE: as in other countries, France introduced advanced practice nursing to respond to the Public Health challenge of improving access to quality health care in the context of increasing chronic disease prevalence and limited resource allocation. Facilitating its integration in the healthcare provision landscape seems paramount.


Assuntos
Prática Avançada de Enfermagem , Humanos , Adulto , Estudos Transversais , Atenção à Saúde , Emprego , Inquéritos e Questionários
8.
J Int Neuropsychol Soc ; 18(3): 501-10, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22433474

RESUMO

Many studies have assessed visual short-term memory (VSTM) abilities in children with specific language impairment (SLI), with contrasting results: some studies observed preserved VSTM capacities, while others reported impaired VSTM. The present study explores the hypothesis that the complexity of the visual information to be encoded and stored might underlie these discrepancies. Four VSTM conditions were administered to a group of 15 children with SLI, as well as to two groups of typically developing children, matched for chronological age and for VSTM capacity for visually simple stimuli, respectively. The stimuli to be remembered varied in their visual similarity and in the number of their visual features. Across the four VSTM conditions, children with SLI showed significantly reduced performance relative to an age-matched control group, and they were more strongly affected by visual similarity and number of features when compared to a control group matched for VSTM capacity for visually simple stimuli. The present results support the hypothesis that stimulus complexity is a determining factor of the poor VSTM performances in children with SLI.


Assuntos
Percepção de Forma/fisiologia , Transtornos do Desenvolvimento da Linguagem/complicações , Transtornos da Memória/etiologia , Memória de Curto Prazo/fisiologia , Adolescente , Criança , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Estimulação Luminosa
9.
J Fluency Disord ; 68: 105830, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33662867

RESUMO

PURPOSE: Many school-age children and adolescents who stutter experience the fear of public speaking. Treatment implications include the need to address this problem. However, it is not always possible to train repeatedly in front of a real audience. The present study aimed to assess the relevance of using a virtual classroom in clinical practice with school-age children and adolescents who stutter. METHODS: Ten children and adolescents who stutter (aged 9-17 years old) had to speak in three different situations: in front of a real audience, in front of a virtual class and in an empty virtual apartment using a head-mounted display. We aimed to assess whether the self-rated levels of anxiety while speaking in front of a virtual audience reflect the levels of anxiety reported while speaking in front of a live audience, and if the stuttering level while speaking to a virtual class reflects the stuttering level while speaking in real conditions. RESULTS: Results show that the real audience creates higher anticipatory anxiety than the virtual class. However, both the self-reported anxiety levels and the stuttering severity ratings when talking in front of a virtual class did not differ from those observed when talking to a real audience, and were significantly higher than when talking in an empty virtual apartment. CONCLUSION: Our results support the feasibility and relevance of using a virtual classroom to expose school-age children and adolescents who stutter to a feared situation during cognitive behavioral therapy targeting the fear of public speaking.


Assuntos
Gagueira , Adolescente , Ansiedade , Transtornos de Ansiedade , Criança , Humanos , Instituições Acadêmicas , Fala
10.
Clin Res Hepatol Gastroenterol ; 45(3): 101650, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33609787

RESUMO

Hepatocellular carcinoma (HCC) mostly occurs in patients with chronic liver disease (CLD). HCC treatment may have a direct impact on CLD prognosis. HCC management can therefore become complex, involving multiple health care providers, such as oncologists, hepatologists, radiologists, and surgeons. In France, dedicated nurses have been involved in patient care pathways. Their impact is poorly documented. PURPOSE: To determine the country-wide distribution of HCC nurse coordinators in French health care settings and to describe their roles and responsibilities. PATIENTS AND METHODS: A survey using a multi-item questionnaire (including center characteristics, nurse coordinator characteristics, and quality indicators such as patient care pathway initiation timeline, scheduled length of hospital stay, diagnostic disclosure process) was conducted. All French liver cancer centers planning to participate in a prospective national cohort study for patients with HCC (CHIEF Cohort) were invited to take part in the survey. Bivariate analysis compared centers with a nurse coordinator to those without. RESULTS: Among the 42 of 72 centers that replied, 14 treated fewer than 75 HCC patients. Treatment mostly took place in hepatology units (34/42). Sixteen nurse coordinators were part of the health care team in 13 of the 42 centers. Among these 13 centers, 11 were university hospitals and 11 followed more than 75 patients per year. The median number of patients followed in these centers was 300 (min-max 44-600) in 2017. All nurse coordinators were involved in providing patient information and counseling. Other roles included treatment monitoring (13/16), care coordination (12/16), psychological support (12/16) and treatment planning (11/16). Thirteen nurse coordinators conducted diagnostic disclosure nurse consultations; seven conducted initial patient contact consultations; and six held outpatient nurse consultations, with wide heterogeneity between centers. The presence of a nurse coordinator was associated with completion of the full diagnostic disclosure process (p = 0.045). CONCLUSION: In France, nurse coordinators for HCC patient pathway management are present mainly in university hepatology units with a caseload of more than 75 patients per year. All provide patient information and counseling but their roles in care coordination, patient support and holistic assessment are heterogeneous and not standardized.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Enfermeiros Administradores , Carcinoma Hepatocelular/terapia , Estudos de Coortes , França , Humanos , Neoplasias Hepáticas/terapia , Equipe de Assistência ao Paciente , Estudos Prospectivos , Inquéritos e Questionários
11.
J Vasc Res ; 47(4): 355-66, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20016209

RESUMO

BACKGROUND/AIM: The intraluminal thrombus (ILT) is considered to participate in abdominal aortic aneurysm (AAA) evolution. To assess whether this role proceeds via ILT influence on biological activity of the AAA wall, we studied the relationships between the levels of some relevant proteases and microparticles (MP) released by ILT versus wall in rat experimental AAAs. METHODS AND RESULTS: Two weeks after elastase perfusion, ILT and AAA wall were incubated in cell culture medium and studies were performed on conditioned media. As shown by gelatin zymography, ILT released higher amounts of MMP9 than the wall, whereas the level of MMP2 activation (active/pro) was similar. Levels of elastase and urokinase plasminogen activator, plasmin and MPs, determined, respectively, by casein zymography, substrate hydrolysis and flow cytometry, were higher in ILT than in wall. Aneurysm diameter positively correlated with wall MMP9 levels, MMP2 activation, plasmin activity and MP release. Moreover, wall and ILT levels of pro- and active forms of MMP2, elastase and plasmin were positively correlated. Wall levels of MMP2 activation and plasmin activity also correlated with ILT weight. CONCLUSION: The present data suggest that, in this experimental model, ILT may contribute to AAA evolution via its influence on the level of aneurysmal wall protease activity.


Assuntos
Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/metabolismo , Ruptura Aórtica/metabolismo , Trombose/metabolismo , Animais , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/patologia , Ruptura Aórtica/induzido quimicamente , Ruptura Aórtica/patologia , Apoptose , Micropartículas Derivadas de Células/metabolismo , Meios de Cultivo Condicionados/metabolismo , Modelos Animais de Doenças , Fibrinolisina/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Elastase Pancreática/metabolismo , Ratos , Ratos Endogâmicos Lew , Trombose/induzido quimicamente , Trombose/patologia , Técnicas de Cultura de Tecidos , Ativador de Plasminogênio Tipo Uroquinase/metabolismo
12.
Histopathology ; 57(6): 917-32, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21166705

RESUMO

AIMS: Thoracic ascending aortic aneurysms (TAA) are characterized by elastic fibre breakdown and cystic medial degeneration within the aortic media, associated with progressive smooth muscle cell (SMC) rarefaction. The transforming growth factor (TGF)-ß/Smad2 signalling pathway is involved in this process. Because the pericellular fibrinolytic system activation is able to degrade adhesive proteins, activate matrix metalloproteinase (MMP), induce SMC disappearance and increase the bioavailability of TGF-ß, the aim was to investigate the plasminergic system in TAA. METHODS AND RESULTS: Ascending aortas [21 controls and 19 TAAs (of three different aetiologies)] were analysed. Immunohistochemistry showed accumulation of t-PA, u-PA and plasmin in TAAs, associated with residual SMCs. Overexpression of t-PA and u-PA was confirmed by reverse transcription-polymerase chain reaction (RT-PCR), immunoblotting and zymography on TAA extracts and culture medium conditioned by TAA. Plasminogen was present on the SMC surface and inside cytoplasmic vesicles, but plasminogen mRNA was undetectable in the TAA medial layer. Plasmin-antiplasmin complexes were detected in TAA-conditioned medium and activation of the fibrinolytic system was associated with increased fibronectin turnover. Fibronectin-related material was detected immunohistochemically in dense clumps around SMCs and colocalized with latent TGF-ß binding protein-1. CONCLUSIONS: The fibrinolytic pathway could play a critical role in TAA progression, via direct or indirect impact on ECM and consecutive modulation of TGF-ß bioavailability.


Assuntos
Aorta/metabolismo , Aneurisma da Aorta Torácica/metabolismo , Ativador de Plasminogênio Tecidual/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Adulto , Idoso , Aneurisma da Aorta Torácica/genética , Western Blotting , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/fisiologia , Proteína Smad2/genética , Proteína Smad2/metabolismo , Ativador de Plasminogênio Tecidual/genética , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/genética
13.
Cortex ; 45(6): 708-20, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19084832

RESUMO

This study re-explored the nature of verbal short-term memory (STM) deficits in children with specific language impairment (SLI), by distinguishing item and serial order STM processes. Recent studies have shown serial order STM capacity to be a critical determinant of language development, relative to item STM. In Experiment 1, 12 children with SLI, 12 age-matched children and 12 language-matched children were administered serial order recognition and reconstruction tasks. Experiment 2 assessed implicit serial learning abilities via a Hebb learning task. The SLI group showed impaired performance for the serial order reconstruction and recognition tasks, relative to language-matched and/or age-matched control groups. However, normal serial position effects were observed in all SLI children in the serial order reconstruction task, suggesting normal coding of serial position information. Similarly, performance on the Hebb serial learning task was at chronological age appropriate levels. Experiment 3 showed that the group differences observed for the serial order STM tasks in Experiment 1 disappeared when the SLI group was compared to a mental age-matched control group. Experiment 4 showed similar performance levels in the SLI group and the mental age-matched control group for a nonword recognition task assessing item STM capacities. This study shows that children with SLI have no specific impairments for serial order and item STM components but that poorer general cognitive efficiency is related to functional limitations in verbal STM tasks. The data are in line with limited information processing accounts of SLI.


Assuntos
Transtornos do Desenvolvimento da Linguagem/fisiopatologia , Memória de Curto Prazo/fisiologia , Reconhecimento Psicológico/fisiologia , Aprendizagem Seriada/fisiologia , Aprendizagem Verbal/fisiologia , Análise de Variância , Estudos de Casos e Controles , Criança , Linguagem Infantil , Feminino , Humanos , Desenvolvimento da Linguagem , Masculino , Análise por Pareamento , Conceitos Matemáticos , Modelos Psicológicos , Valores de Referência
14.
J Leukoc Biol ; 82(6): 1420-9, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17827339

RESUMO

The pathological remodeling of the arterial wall in atherosclerosis involves protease activities, which play a major role in complications via plaque rupture. Circulating leukocytes and particularly neutrophils have been shown to be an independent predictor of recurrent ischemic events. However, neutrophils are poorly documented within atherosclerotic plaques. We hypothesized that intraplaque hemorrhage could convey neutrophils into the lesion, spreading into the necrotic core, thus participating in its protease enrichment. One hundred human carotid endarterectomy specimens were dissected into culprit-stenosing plaques (CPs) and adjacent noncomplicated plaques. Half of CPs exhibited hemorrhage, which was confirmed by the release of hemoglobin. Pro- and active forms of matrix metalloproteinase-9 (MMP-9) were increased in media conditioned by hemorrhagic plaques. Higher levels of lipocalin [neutrophil gelatinase-associated lipocalin (NGAL)]/MMP-9 complexes, specifically released by neutrophils, were also found in conditioned media from plaques with hemorrhage. Immunohistochemical analysis of the corresponding carotid samples showed that neutrophil markers such as elastase, NGAL/MMP-9, CD66b, and proteinase 3 colocalized with blood constituents (i.e., hemoglobin, plasminogen). All markers of neutrophil degranulation were positively correlated in CP-conditioned media (alpha1-antitrypsin/elastase complexes, myeloperoxidase, and alpha-defensins), and higher levels came from CPs containing intraplaque hemorrhages. Addition of an elastase inhibitor at the time of incubation led to a decrease in the proMMP-9 activation in CPs, suggesting cross-talk between proteases released by neutrophils. Finally, we found that neovessels observed at the interface between cap and core exhibit an activated endothelium, which may favor leukocyte diapedesis. Our study thus provides evidence for the involvement of neutrophils in plaque vulnerability.


Assuntos
Aterosclerose/enzimologia , Endopeptidases/metabolismo , Hemorragia/enzimologia , Neutrófilos/enzimologia , Trombose/enzimologia , Biomarcadores/metabolismo , Fatores Quimiotáticos/metabolismo , Meios de Cultivo Condicionados , Ativação Enzimática , Humanos , Leucócitos/enzimologia , Leucócitos/patologia , Metaloproteinase 9 da Matriz/metabolismo , Elastase Pancreática/metabolismo
15.
Atherosclerosis ; 191(1): 1-10, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16713600

RESUMO

The pathological remodeling of the arterial wall in atherosclerosis involves protease activities, which play a major role in complications, through plaque rupture. Here, we investigated the release of active proteases by human carotid plaques in relation to (1) the degree of lesion complexity and (2) their compartmentalization between cap, core and media. Eighty human carotid endarterectomy specimens were dissected into culprit stenosing (CPs) and adjacent non-complicated/non-stenosing plaques (NPs). Thirty-five additional CPs were microdissected into cap, core and media. All specimens were compared to control non-atherosclerotic endarteries for the release of components of the plasminogen/plasmin system and matrix metalloproteinases (MMPs). Results show a greater release of the plasminogen activators (PAs), plasmin and active MMPs by CPs compared to NPs, whereas healthy arteries released even lower levels. Furthermore, we highlight a functional interaction between these proteases in human atherosclerotic tissues and more importantly, we demonstrate that the core constitutes the main source of protease activities within CPs. Together, these results suggest that CPs generate plasmin, mainly in the core, which could in turn participate in MMP activation and the onset of complications.


Assuntos
Artérias Carótidas/fisiopatologia , Doenças das Artérias Carótidas/enzimologia , Estenose das Carótidas/enzimologia , Fibrinolisina/metabolismo , Metaloproteinases da Matriz/metabolismo , Ativadores de Plasminogênio/metabolismo , Doenças das Artérias Carótidas/patologia , Doenças das Artérias Carótidas/fisiopatologia , Estenose das Carótidas/patologia , Estenose das Carótidas/fisiopatologia , Endarterectomia das Carótidas , Humanos , Peptídeo Hidrolases/metabolismo
16.
Arterioscler Thromb Vasc Biol ; 26(6): 1337-43, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16574891

RESUMO

OBJECTIVE: Because culprit atherosclerotic plaques contain proteases, we hypothesized that the diminished heat shock protein 27 (HSP27) released by atherosclerotic plaques could be due to proteolysis. We assessed the role of HSP27 in human vascular smooth muscle cells (VSMCs) under proteolytic injury. METHODS AND RESULTS: Active plasmin is present in culprit atherosclerotic plaques. Recombinant HSP27 was cleaved by plasmin and this effect was prevented by different inhibitors. Fragments and aggregated forms of HSP27 appeared after incubation of mammary control endarteries with plasmin. Coincubation of atherosclerotic plaques with recombinant HSP27 or mammary endarteries led to HSP27 proteolysis. After incubation of VSMCs with plasmin, HSP27 was overexpressed, phosphorylated, aggregated, and redistributed from the cytoskeleton to the cytosol, nucleus, and cell membrane. Plasmin-induced VSMC apoptosis was significantly higher in VSMCs treated by HSP27 siRNA. Immunohistochemical analysis of atherosclerotic plaques showed that plasmin(ogen) and apoptotic cells are localized in the core/shoulder whereas HSP27 and VSMCs are mainly expressed in the cap/media. CONCLUSIONS: Extracellular HSP27 can be degraded by enzymes released from atherosclerotic plaques and may reflect a proteolytic imbalance. Intracellular HSP27 downregulation decreases VSMCs resistance to proteolytically-induced apoptosis. HSP27 might play a pivotal role in the prevention of plaque instability and rupture.


Assuntos
Aterosclerose/fisiopatologia , Proteínas de Choque Térmico/metabolismo , Proteínas de Neoplasias/metabolismo , Apoptose , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/fisiopatologia , Células Cultivadas , Fibrinolisina/metabolismo , Fibrinolisina/farmacologia , Proteínas de Choque Térmico HSP27 , Humanos , Chaperonas Moleculares , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Técnicas de Cultura de Tecidos
19.
Circulation ; 110(15): 2216-9, 2004 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-15249501

RESUMO

BACKGROUND: We hypothesized that normal and pathological vessel walls display a differential pattern of secreted proteins. We have recently set up the conditions for comparing secretomes from carotid atherosclerotic plaques and control arteries using a proteomic approach to assess whether differentially secreted proteins could represent markers for atherosclerosis. METHODS AND RESULTS: Normal endartery segments and different regions of endarterectomy pieces (noncomplicated/complicated plaques) were incubated in protein-free medium, and the released proteins were analyzed by 2D electrophoresis (2-DE). Among the differently secreted proteins, we have identified heat shock protein-27 (HSP27). Surprisingly, compared with control arteries, HSP27 release was drastically decreased in atherosclerotic plaques and barely detectable in complicated plaque supernatants. HSP27 was expressed primarily by intact vascular cells of normal arteries and carotid plaques (immunohistochemistry). Plasma detection of soluble HSP27 showed that circulating HSP27 levels are significantly decreased in the blood of patients with carotid stenosis relative to healthy subjects (0.19 [0.1 to 1.95] versus 83 [71.8 to 87.8]) ng/mL, P<0.0001). CONCLUSIONS: HSP27 secretion is decreased in complicated atherosclerotic plaques, and sHSP27 plasma levels are decreased in atherosclerotic patients compared with healthy subjects. Plasma sHSP27 levels could be a potential index of atherosclerosis, although further validation is needed in large patient cohorts.


Assuntos
Doenças das Artérias Carótidas/fisiopatologia , Proteínas de Choque Térmico/metabolismo , Proteínas de Neoplasias/metabolismo , Proteômica , Idoso , Artérias Carótidas/metabolismo , Artérias Carótidas/patologia , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/cirurgia , Cromatografia de Afinidade , Meios de Cultivo Condicionados/química , Endarterectomia das Carótidas , Feminino , Artéria Femoral/metabolismo , Artéria Femoral/patologia , Proteínas de Choque Térmico HSP27 , Proteínas de Choque Térmico/sangue , Proteínas de Choque Térmico/deficiência , Humanos , Masculino , Pessoa de Meia-Idade , Chaperonas Moleculares , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/deficiência , Técnicas de Cultura de Órgãos , Fosforilação , Isoformas de Proteínas/análise , Processamento de Proteína Pós-Traducional , Solubilidade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
20.
PLoS One ; 10(11): e0143144, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26599408

RESUMO

BACKGROUND: Aortic diseases are diverse and involve a multiplicity of biological systems in the vascular wall. Aortic dissection, which is usually preceded by aortic aneurysm, is a leading cause of morbidity and mortality in modern societies. Although the endothelium is now known to play an important role in vascular diseases, its contribution to aneurysmal aortic lesions remains largely unknown. The aim of this study was to define a reliable methodology for the isolation of aortic intimal and adventitial endothelial cells in order to throw light on issues relevant to endothelial cell biology in aneurysmal diseases. METHODOLOGY/PRINCIPAL FINDINGS: We set up protocols to isolate endothelial cells from both the intima and the adventitia of human aneurysmal aortic vessel segments. Throughout the procedure, analysis of cell morphology and endothelial markers allowed us to select an endothelial fraction which after two rounds of expansion yielded a population of >90% pure endothelial cells. These cells have the features and functionalities of freshly isolated cells and can be used for biochemical studies. The technique was successfully used for aortic vessel segments of 20 patients and 3 healthy donors. CONCLUSIONS/SIGNIFICANCE: This simple and highly reproducible method allows the simultaneous preparation of reasonably pure primary cultures of intimal and adventitial human endothelial cells, thus providing a reliable source for investigating their biology and involvement in both thoracic aneurysms and other aortic diseases.


Assuntos
Aorta Torácica/patologia , Separação Celular/métodos , Células Endoteliais/patologia , Endotélio Vascular/patologia , Túnica Íntima/patologia , Aorta Torácica/metabolismo , Aneurisma Aórtico/patologia , Aneurisma Aórtico/cirurgia , Biomarcadores , Proliferação de Células , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Humanos , Imunofenotipagem , Fenótipo , Cultura Primária de Células , Reprodutibilidade dos Testes , Túnica Íntima/metabolismo
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