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1.
Int J Equity Health ; 22(1): 171, 2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37653472

RESUMO

BACKGROUND: The COVID-19 pandemic substantially magnified the inequity gaps among vulnerable populations. Both public health (PH) and primary health care (PHC) have been crucial in addressing the challenges posed by the pandemic, especially in the area of vulnerable populations. However, little is known about the intersection between PH and PHC as a strategy to mitigate the inequity gap. This study aims to assess the collaboration between PHC and PH with a focus on addressing the health needs of vulnerable populations during the COVID-19 pandemic across jurisdictions. METHODS: We analyzed and compared data from jurisdictional reports of COVID-19 pandemic responses in PHC and PH in Belgium, Canada (Ontario), Germany, Italy, Japan, the Netherlands, Norway, and Spain from 2020 to 2021. RESULTS: Four themes emerge from the analysis: (1) the majority of the countries implemented outreach strategies targeting vulnerable groups as a means to ensure continued access to PHC; (2) digital assessment in PHC was found to be present across all the countries; (3) PHC was insufficiently represented at the decision-making level; (4) there is a lack of clear communication channels between PH and PHC in all the countries. CONCLUSIONS: This study identified opportunities for collaboration between PHC and PH to reduce inequity gaps and to improve population health, focusing on vulnerable populations. The COVID-19 response in these eight countries has demonstrated the importance of an integrated PHC system. Consequently, the development of effective strategies for responding to and planning for pandemics should take into account the social determinants of health in order to mitigate the unequal impact of COVID-19. Careful, intentional coordination between PH and PHC should be established in normal times as a basis for effective response during future public health emergencies. The pandemic has provided significant insights on how to strengthen health systems and provide universal access to healthcare by fostering stronger connections between PH and PHC.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Países Desenvolvidos , Pandemias , Saúde Pública , Desigualdades de Saúde , Ontário , Atenção Primária à Saúde
2.
BMC Pulm Med ; 22(1): 457, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36456965

RESUMO

BACKGROUND: Asthma education programs (AEPs) have been shown to increase quality of life and reduce emergency treatments and hospital admissions. Despite the proven benefits, only a minority of asthma patients attend such programs. To increase the number of educated patients, an online education program (electronic AEP, eAEP) for asthma patients has been developed. The present study aims to investigate the effectiveness of the eAEP in terms of asthma knowledge, asthma control and emergency treatments in general practice settings. METHODS: This is a cluster randomized controlled trial including 100 patients with bronchial asthma from 20 general practices in Bavaria, Germany. General practices will be randomly assigned to either the intervention or control group. Patients in the intervention group will receive access to the eAEP and instructions to complete this program within two weeks. Patients in the control group will receive usual care including a referral to face-to-face AEP (fAEP) by a certified primary care physician or a pulmonologist according to guideline recommendations. Furthermore, patients of both the intervention and control groups will be invited to a follow-up consultation in their general practice after completion of the eAEP and fAEP (three weeks and twelve weeks after study inclusion, respectively) to discuss any open issues. Outcomes for both groups will be assessed at baseline (t0), after two weeks (t1), three months (t2) and six months (t3). The primary outcome is the comparison of asthma knowledge gain between intervention and control groups after completion of the eAEP (two weeks after study inclusion) and fAEP (twelve weeks after study inclusion), respectively. Secondary outcomes include asthma control, frequency of emergency treatments, patient autonomy as well as attitudes towards asthma medication. DISCUSSION: The results of the present trial will provide knowledge about the effectiveness of an online education program for asthma patients compared to usual care in primary care. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00028805 . Registered 22 April 2022.


Assuntos
Asma , Educação a Distância , Medicina Geral , Humanos , Qualidade de Vida , Asma/terapia , Pneumologistas , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
BMC Prim Care ; 24(Suppl 1): 290, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937675

RESUMO

BACKGROUND: Recruitment for surveys has been a great challenge, especially in general practice. METHODS: Here, we reported recruitment strategies, data collection, participation rates (PR) and representativeness of the PRICOV-19 study, an international comparative, cross-sectional, online survey among general practices (GP practices) in 37 European countries and Israel. RESULTS: Nine (24%) countries reported a published invitation; 19 (50%) had direct contact with all GPs/GP practices; 19 (50%) contacted a sample of GPs /GP practices; and 7 (18%) used another invitation strategy. The median participation rate was 22% (IQR = 10%, 28%). Multiple invitation strategies (P-value 0.93) and multiple strategies to increase PR (P-value 0.64) were not correlated with the PR. GP practices in (semi-) rural areas, GP practices serving more than 10,000 patients, and group practices were over-represented (P-value < 0.001). There was no significant correlation between the PR and strength of the primary care (PC) system [Spearman's r 0.13, 95% CI (-0.24, 0.46); P-value 0.49]; the COVID-19 morbidity [Spearman's r 0.19, 95% CI (-0.14, 0.49); P-value 0.24], or COVID-19 mortality [Spearman's r 0.19, 95% CI (-0.02, 0.58); P-value 0.06] during the three months before country-specific study commencement. CONCLUSION: Our main contribution here was to describe the survey recruitment and representativeness of PRICOV-19, an important and novel study.


Assuntos
COVID-19 , Seleção de Pacientes , Humanos , Estudos Transversais , COVID-19/epidemiologia , Europa (Continente)/epidemiologia , Israel/epidemiologia , Medicina Geral/estatística & dados numéricos , SARS-CoV-2 , Inquéritos e Questionários , Coleta de Dados/métodos
4.
BMC Prim Care ; 25(1): 10, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166677

RESUMO

BACKGROUND: Despite general practitioners' (GPs') key role in Germany`s primary health care, clinical research in general practice is scarce. Clinical research is mainly conducted at inpatient facilities, although their results are rarely transferable. German GPs have no extra time or funding for research, as well as limited research training. To support clinical research in German primary health care, practice-based research networks (PBRNs) are developed. As they will be based on an active involvement of GPs, we need more information on GPs` participation-readiness. The aim of this study was to explore facilitators and barriers to participation in the Bavarian Research Practice Network (BayFoNet) from the GPs`perspective before clinical trials will be performed. METHODS: We have performed semi-structured qualitative interviews with a purposive sample of 20 Bavarian GPs in 2022 under the application of the consolidated framework for implementation research (CFIR). Transcriptions were analysed according to Kuckartz` qualitative content analysis. The five domains of the CFIR framework served as initial deductive codes. RESULTS: N = 14 interviewees already agreed to participate in BayFoNet, whereas n = 6 interviewees opted not to participate in BayFoNet at the time of data collection. Main facilitators to conduct clinical research within BayFoNet were the motivation to contribute to evidence strength and quality in general practice, professional development and training of practice staff, as well as networking. Barriers for an active participation were bad experiences with previous clinical studies and lack of resources. CONCLUSIONS: PBRNS in Germany have to be promoted and the entire practice team has to be involved at an early stage of development. Professional training of general practice staff and a living network might enhance engagement. Participatory approaches could help to develop acceptable and feasible study designs. Furthermore, PBRNs should support patient recruitment and data collection in general practices and disseminate the results of their research projects regularly to maintain GPs` engagement. TRIAL REGISTRATION: DRKS00028805, NCT05667207.


Assuntos
Medicina Geral , Clínicos Gerais , Humanos , Motivação , Atitude do Pessoal de Saúde , Medicina Geral/métodos , Pesquisa Qualitativa
5.
BMJ Open ; 14(3): e079345, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553055

RESUMO

INTRODUCTION: Uncomplicated urinary tract infections (uUTIs) in women are common infections encountered in primary care. Evidence suggests that rapid point-of-care tests (POCTs) to detect bacteria and erythrocytes in urine at presentation may help primary care clinicians to identify women with uUTIs in whom antibiotics can be withheld without influencing clinical outcomes. This pilot study aims to provide preliminary evidence on whether a POCT informed management of uUTI in women can safely reduce antibiotic use. METHODS AND ANALYSIS: This is an open-label two-arm parallel cluster-randomised controlled pilot trial. 20 general practices affiliated with the Bavarian Practice-Based Research Network (BayFoNet) in Germany were randomly assigned to deliver patient management based on POCTs or to provide usual care. POCTs consist of phase-contrast microscopy to detect bacteria and urinary dipsticks to detect erythrocytes in urine samples. In both arms, urine samples will be obtained at presentation for POCTs (intervention arm only) and microbiological analysis. Women will be followed-up for 28 days from enrolment using self-reported symptom diaries, telephone follow-up and a review of the electronic medical record. Primary outcomes are feasibility of patient enrolment and retention rates per site, which will be summarised by means and SDs, with corresponding confidence and prediction intervals. Secondary outcomes include antibiotic use for UTI at day 28, time to symptom resolution, symptom burden, number of recurrent and upper UTIs and re-consultations and diagnostic accuracy of POCTs versus urine culture as the reference standard. These outcomes will be explored at cluster-levels and individual-levels using descriptive statistics, two-sample hypothesis tests and mixed effects models or generalised estimation equations. ETHICS AND DISSEMINATION: The University of Würzburg institutional review board approved MicUTI on 16 December 2022 (protocol n. 109/22-sc). Study findings will be disseminated through peer-reviewed publications, conferences, reports addressed to clinicians and the local citizen's forums. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT05667207.


Assuntos
Antibacterianos , Infecções Urinárias , Feminino , Humanos , Antibacterianos/uso terapêutico , Microscopia , Projetos Piloto , Sistemas Automatizados de Assistência Junto ao Leito , Atenção Primária à Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções Urinárias/diagnóstico , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , Estudos Multicêntricos como Assunto
6.
BMC Prim Care ; 24(Suppl 1): 207, 2023 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-37821802

RESUMO

BACKGROUND: The international study PRICOV-19 aims to assess the impact of the COVID-19 pandemic on the organisation of primary health care. The German part focuses on German general practitioners during the second wave of the COVID-19 pandemic. This paper addresses the following research questions: (1) How were changes in tasks on primary care and patient treatment perceived by GPs?, (2) What was the role of GPs during the pandemic, and how was their wellbeing?, (3) How did GPs perceive health policy measures?, and, (4) What influenced the attitudes of GPs on health policy measures? METHODS: This study pursues a multi-country cross-sectional design. Data collection took place throughout Germany from 01.02. to 28.02.2021 with a quantitative online questionnaire consisting of 53 items. The questionnaire was analysed through descriptive and inferential analyses using correlation and multiple regression models. RESULTS: The response rate was 20.4% (n = 349). The respondents were mainly GPs (59.6%) in single practices (62.5%) with a mean work experience of 15 to 20 years. GPs experienced a change in their work and practice organisation (80.3%). They felt a high responsibility (70.6%) and found their work has become more meaningful to them (76%). They also saw a lack of political support (75.2%) and that the measures taken by the government overburdened the daily practice (66.4%). Not many GPs were at risk of being distressed (53.4%) but rated the health policies rather negatively (60%). The multiple regression showed, the more GPs were exposed to risk of distress, the worse they assessed the government's measures. CONCLUSION: GPs perceived their work as relevant and felt confident they could fulfil their tasks, but noticed that health policy initially hardly supported the outpatient sector. Health policies should increase their competence in relation to primary care, ensure its needs and consider an active inclusion of GPs in preparedness plans.


Assuntos
COVID-19 , Clínicos Gerais , Humanos , COVID-19/epidemiologia , Estudos Transversais , Pandemias , Inquéritos e Questionários , Governo
7.
PLoS One ; 18(3): e0282504, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36930662

RESUMO

BACKGROUND: The international collaboration study PRICOV-19 -Primary Health Care in times of COVID-19 aims to assess the impact of the COVID-19 pandemic on the organisation of primary health care. The German part focuses on the subjective perceptions of general practitioners on primary health care and the impact of political measures during the second wave of the COVID-19 pandemic. Within this survey, the "open text field" of the questionnaire was utilised remarkably frequently and extensively by the respondents. It became clear that the content that was named needed to be analysed in an exploratory manner. Accordingly, this paper addresses the following question: What preoccupies general practitioners in Germany during COVID-19 that we have not yet asked them enough? METHODS: The data collection took place throughout Germany from 01.02.2021 to 28.02.2021with a quantitative online questionnaire consisting of 53 items arranged across six topics as well as an "open text field" for further comments. The questionnaire's open text field was analysed following the premises of the qualitative content analysis. RESULTS: The topics discussed by the respondents were: insufficient support from health policies, not being prioritised and involved in the vaccination strategy, feeling insufficient prepared, that infrastructural changes and financial concerns threatened the practice, and perceiving the own role as important, as well as that health policies affected the wellbeing of the respondents. One of the main points was the way general practitioners were not sufficiently acknowledged for their contribution to ensuring high-quality care during the pandemic. DISCUSSION: German general practitioners perceived their work and role as highly relevant during the COVID-19 pandemic. In controversy with their perception, they described political conditions in which they were the ones who contributed significantly to the fight against the pandemic but were not given enough recognition.


Assuntos
COVID-19 , Clínicos Gerais , Humanos , COVID-19/epidemiologia , Pandemias , Coleta de Dados , Atenção Primária à Saúde
8.
Artigo em Inglês | MEDLINE | ID: mdl-36833862

RESUMO

The COVID-19 pandemic disproportionately affected vulnerable populations' access to health care. By proactively reaching out to them, general practices attempted to prevent the underutilization of their services. This paper examined the association between practice and country characteristics and the organization of outreach work in general practices during COVID-19. Linear mixed model analyses with practices nested in countries were performed on the data of 4982 practices from 38 countries. A 4-item scale on outreach work was constructed as the outcome variable with a reliability of 0.77 and 0.97 at the practice and country level. The results showed that many practices set up outreach work, including extracting at least one list of patients with chronic conditions from their electronic medical record (30.1%); and performing telephone outreach to patients with chronic conditions (62.8%), a psychological vulnerability (35.6%), or possible situation of domestic violence or a child-rearing situation (17.2%). Outreach work was positively related to the availability of an administrative assistant or practice manager (p < 0.05) or paramedical support staff (p < 0.01). Other practice and country characteristics were not significantly associated with undertaking outreach work. Policy and financial interventions supporting general practices to organize outreach work should focus on the range of personnel available to support such practice activities.


Assuntos
COVID-19 , Medicina Geral , Humanos , Estudos Transversais , Pandemias , Reprodutibilidade dos Testes , Doença Crônica
9.
Am J Physiol Lung Cell Mol Physiol ; 303(5): L425-38, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22707616

RESUMO

Uncontrolled transmigration of polymorphonuclear leukocytes (PMNs) into the different compartments of the lungs (intravascular, interstitial, alveolar) is a critical event in the early stage of acute lung injury and acute respiratory distress syndrome. Adenosine receptor A(2b) is highly expressed in the inflamed lungs and has been suggested to mediate cell trafficking. In a murine model of LPS-induced lung inflammation, we investigated the role of A(2b) on migration of PMNs into the different compartments of the lung. In A(2b)(-/-) mice, LPS-induced accumulation of PMNs was significantly higher in the interstitium, but not in the alveolar space. In addition, pulmonary clearance of PMNs was delayed in A(2b)(-/-) mice. Using chimeric mice, we identified A(2b) on hematopoietic cells as crucial for PMN migration. A(2b) did not affect the release of relevant chemokines into the alveolar space. LPS-induced microvascular permeability was under the control of A(2b) on both hematopoietic and nonhematopoietic cells. Activation of A(2b) on endothelial cells also reduced formation of LPS-induced stress fibers, highlighting its role for endothelial integrity. A specific A(2b) agonist (BAY 60-6583) was effective in decreasing PMN migration into the lung interstitium and microvascular permeability. In addition, in vitro transmigration of human PMNs through a layer of human endothelial or epithelial cells was A(2b) dependent. Activation of A(2b) on human PMNs reduced oxidative burst activity. Together, our results demonstrate anti-inflammatory effects of A(2b) on two major characteristics of acute lung injury, with a distinct role of hematopoietic A(2b) for cell trafficking and endothelial A(2b) for microvascular permeability.


Assuntos
Células da Medula Óssea/metabolismo , Lipopolissacarídeos/farmacologia , Pulmão/patologia , Neutrófilos/fisiologia , Pneumonia/metabolismo , Receptor A2B de Adenosina/metabolismo , Migração Transendotelial e Transepitelial , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Agonistas do Receptor A2 de Adenosina/farmacologia , Aminopiridinas/farmacologia , Animais , Transplante de Medula Óssea , Líquido da Lavagem Broncoalveolar , Permeabilidade Capilar , Contagem de Células , Células Cultivadas , Quimiocinas/metabolismo , Citoesqueleto/metabolismo , Expressão Gênica , Regulação da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neutrófilos/efeitos dos fármacos , Pneumonia/imunologia , Pneumonia/patologia , Receptor A2B de Adenosina/genética , Receptor A2B de Adenosina/fisiologia , Explosão Respiratória
10.
J Immunol ; 185(7): 4374-84, 2010 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-20729330

RESUMO

Extracellular adenosine and adenosine receptors are critically involved in various inflammatory pathways. Adenosine receptor A1 (A1AR) has been implicated in mediating transmigration of leukocytes to sites of inflammation. This study was designed to characterize the role of A1AR in a murine model of LPS-induced lung injury. LPS-induced transmigration of polymorphonuclear cells (PMNs) and microvascular permeability was elevated in A1AR(-/-) mice. Pretreatment of wild-type mice with the specific A1AR agonist 2'Me-2-chloro-N6-cyclopentyladenosine attenuated PMN accumulation in the interstitium and alveolar space as well as microvascular permeability. Lower PMN counts in the lungs of pretreated wild-type mice were associated with reduced amounts of the chemotactic cytokines TNF-α, IL-6, and CXCL2/3 in the bronchoalveolar lavage. Pretreatment was only effective when A1AR was expressed on hematopoietic cells as demonstrated in chimeric mice. These findings were confirmed by in vitro transmigration assays demonstrating that chemokine-induced transmigration of PMNs was reduced when PMNs but not when pulmonary endothelial or alveolar epithelial cells were pretreated. 2'Me-2-chloro-N6-cyclopentyladenosine prevented pulmonary endothelial but not epithelial cells from LPS-induced cellular remodeling and cell retraction. Our data reveal what we believe to be a previously unrecognized distinct role of A1AR for PMN trafficking and endothelial integrity in a model of acute lung injury.


Assuntos
Permeabilidade Capilar/imunologia , Quimiotaxia de Leucócito/imunologia , Lesão Pulmonar/metabolismo , Neutrófilos/metabolismo , Receptor A1 de Adenosina/metabolismo , Animais , Western Blotting , Separação Celular , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Lipopolissacarídeos/toxicidade , Lesão Pulmonar/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , RNA Mensageiro/análise , Receptor A1 de Adenosina/imunologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
11.
Artigo em Inglês | MEDLINE | ID: mdl-36430047

RESUMO

The COVID-19 pandemic has had a large and varying impact on primary care. This paper studies changes in the tasks of general practitioners (GPs) and associated staff during the COVID-19 pandemic. Data from the PRICOV-19 study of 5093 GPs in 38 countries were used. We constructed a scale for task changes and performed multilevel analyses. The scale was reliable at both GP and country level. Clustering of task changes at country level was considerable (25%). During the pandemic, staff members were more involved in giving information and recommendations to patients contacting the practice by phone, and they were more involved in triage. GPs took on additional responsibilities and were more involved in reaching out to patients. Problems due to staff absence, when dealt with internally, were related to more task changes. Task changes were larger in practices employing a wider range of professional groups. Whilst GPs were happy with the task changes in practices with more changes, they also felt the need for further training. A higher-than-average proportion of elderly people and people with a chronic condition in the practice were related to task changes. The number of infections in a country during the first wave of the pandemic was related to task changes. Other characteristics at country level were not associated with task changes. Future research on the sustainability of task changes after the pandemic is needed.


Assuntos
COVID-19 , Medicina Geral , Humanos , Idoso , COVID-19/epidemiologia , Pandemias , Recursos Humanos , Atenção Primária à Saúde
12.
PLoS One ; 16(7): e0254644, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34270615

RESUMO

BACKGROUND: Primary care consultation is significantly influenced by communication between the General Practitioner (GP) and their patients. Hypothesising that patient satisfaction can be tested based on an expectation-experience comparison, the aim of this article is to discuss the influence of communication on patient satisfaction. METHODS: A standardised questionnaire was developed striving for a universal primary care survey tool that focuses on patient satisfaction in the context of patient-centred-communication. The sample consisted of 14 German GPs with 80 patients each (n = 1120). Due to the inclusion in an overarching cluster-randomised-study (CRT), the medical practices to be examined were divided into intervention and control groups. The intervention was developed as a reflective training on patient-centred communication. RESULTS: The results in the present sample show no correlation between patient-centred-communication and patient satisfaction. There are also no significant differences between the intervention and control group. DISCUSSION: The results raise the question to what extent patient satisfaction can be shaped significantly through patient-centred-communication. The presented project represents part of the basic research in general medical care research and contributes to the transparent processing of theoretical assumptions. With the results described here, communication models with a focus on patient centredness can be evaluated with regard to their practical relevance and transferability.


Assuntos
Comunicação , Satisfação do Paciente/estatística & dados numéricos , Assistência Centrada no Paciente/organização & administração , Relações Médico-Paciente , Atenção Primária à Saúde/organização & administração , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Assistência Centrada no Paciente/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Melhoria de Qualidade , Encaminhamento e Consulta/organização & administração , Encaminhamento e Consulta/estatística & dados numéricos , Inquéritos e Questionários/estatística & dados numéricos
13.
Am J Physiol Lung Cell Mol Physiol ; 299(4): L502-12, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20639349

RESUMO

Adenosine receptor A(3) (A(3)) regulates directed movement of polymorphonuclear cells (PMNs) to sites of inflammation and has been implicated as a relevant mediator in models of inflammatory diseases. Here, we sought to characterize the role of A(3) in a murine model of lung inflammation. Initial studies revealed that pulmonary A(3) transcript levels were elevated following LPS exposure in vivo. In addition, inhalation of LPS increased the accumulation of PMNs in wild-type and A(3)(-/-) mice in all lung compartments. Pretreatment with the specific A(3)-agonist Cl-IB-MECA significantly decreased migration of PMNs into lung interstitium and alveolar air space of wild-type mice but not of A(3)(-/-) mice. Lower PMN counts were associated with reduced levels of TNF-α and IL-6 in the alveolar space of wild-type mice that received Cl-IB-MECA. In addition, Cl-IB-MECA attenuated LPS-induced microvascular permeability in wild-type mice as assessed by the extravasation of Evans blue. In pulmonary microvascular endothelial cells, Cl-IB-MECA reduced LPS-induced cytoskeletal remodeling and cell retraction, consistent with a specific role of A(3) for maintaining endothelial integrity. Migratory activity of human PMNs across an endothelial or epithelial monolayer was reduced when A(3) was activated on PMNs. Studies in chimeric mice, however, revealed that Cl-IB-MECA required A(3) on both hematopoietic and nonhematopoietic cells to reduce transmigration in vivo. Together, our results shed new light on the role of A(3) in LPS-induced PMN trafficking in the lung and suggest pharmacological modulation of A(3)-dependent pathways as a promising approach in lung inflammation.


Assuntos
Lipopolissacarídeos/farmacologia , Pulmão/metabolismo , Pneumonia/patologia , Receptor A3 de Adenosina/fisiologia , Adenosina/análogos & derivados , Adenosina/farmacologia , Agonistas do Receptor A3 de Adenosina , Animais , Apoptose , Western Blotting , Permeabilidade Capilar , Movimento Celular , Citometria de Fluxo , Humanos , Técnicas Imunoenzimáticas , Pulmão/irrigação sanguínea , Pulmão/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pneumonia/induzido quimicamente , Pneumonia/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
14.
FASEB J ; 23(2): 473-82, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18838482

RESUMO

Extracellular adenosine has been implicated as anti-inflammatory signaling molecule during acute lung injury (ALI). The main source of extracellular adenosine stems from a coordinated two-step enzymatic conversion of precursor nucleotides via the ecto-apyrase (CD39) and the ecto-5'-nucleotidase (CD73). In the present study, we hypothesized a critical role of CD39 and CD73 in mediating pulmonary neutrophil (PMN) transmigration during lipopolysaccharide (LPS) -induced lung injury. Initial studies revealed that pulmonary CD39 and CD73 transcript levels were elevated following LPS exposure in vivo. Moreover, LPS-induced accumulation of PMN into the lungs was enhanced in cd39(-/-) or cd73(-/-) mice, particularly into the interstitial and intra-alveolar compartment. Such increases in PMN trafficking were accompanied by corresponding changes in alveolar-capillary leakage. Similarly, inhibition of extracellular nucleotide phosphohydrolysis with the nonspecific ecto-nucleoside-triphosphate-diphosphohydrolases inhibitor POM-1 confirmed increased pulmonary PMN accumulation in wild-type, but not in gene-targeted mice for cd39 or cd73. Finally, treatment with apyrase or nucleotidase was associated with attenuated pulmonary neutrophil accumulation and pulmonary edema during LPS-induced lung injury. Taken together, these data reveal a previously unrecognized role for CD39 and CD73 in attenuating PMN trafficking into the lungs during LPS-induced lung injury and suggest treatment with their soluble compounds as a therapeutic strategy.


Assuntos
5'-Nucleotidase/metabolismo , Antígenos CD/metabolismo , Apirase/metabolismo , Movimento Celular/efeitos dos fármacos , Pneumopatias/metabolismo , Pneumopatias/patologia , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , 5'-Nucleotidase/deficiência , 5'-Nucleotidase/genética , Adenosina/metabolismo , Animais , Antígenos CD/genética , Apirase/deficiência , Apirase/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Inflamação/metabolismo , Inflamação/patologia , Lipopolissacarídeos/farmacologia , Pneumopatias/induzido quimicamente , Pneumopatias/genética , Masculino , Camundongos , Camundongos Knockout , Nucleotidases/metabolismo , Fosforilação/efeitos dos fármacos , Solubilidade , Transcrição Gênica/efeitos dos fármacos
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