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1.
Allergy ; 79(5): 1089-1122, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38108546

RESUMO

The accumulation of senescent cells drives inflammaging and increases morbidity of chronic inflammatory lung diseases. Immune responses are built upon dynamic changes in cell metabolism that supply energy and substrates for cell proliferation, differentiation, and activation. Metabolic changes imposed by environmental stress and inflammation on immune cells and tissue microenvironment are thus chiefly involved in the pathophysiology of allergic and other immune-driven diseases. Altered cell metabolism is also a hallmark of cell senescence, a condition characterized by loss of proliferative activity in cells that remain metabolically active. Accelerated senescence can be triggered by acute or chronic stress and inflammatory responses. In contrast, replicative senescence occurs as part of the physiological aging process and has protective roles in cancer surveillance and wound healing. Importantly, cell senescence can also change or hamper response to diverse therapeutic treatments. Understanding the metabolic pathways of senescence in immune and structural cells is therefore critical to detect, prevent, or revert detrimental aspects of senescence-related immunopathology, by developing specific diagnostics and targeted therapies. In this paper, we review the main changes and metabolic alterations occurring in senescent immune cells (macrophages, B cells, T cells). Subsequently, we present the metabolic footprints described in translational studies in patients with chronic asthma and chronic obstructive pulmonary disease (COPD), and review the ongoing preclinical studies and clinical trials of therapeutic approaches aiming at targeting metabolic pathways to antagonize pathological senescence. Because this is a recently emerging field in allergy and clinical immunology, a better understanding of the metabolic profile of the complex landscape of cell senescence is needed. The progress achieved so far is already providing opportunities for new therapies, as well as for strategies aimed at disease prevention and supporting healthy aging.


Assuntos
Senescência Celular , Redes e Vias Metabólicas , Humanos , Senescência Celular/efeitos dos fármacos , Animais , Doença Crônica , Inflamação/metabolismo , Inflamação/imunologia , Pneumopatias/etiologia , Pneumopatias/tratamento farmacológico , Pneumopatias/metabolismo , Pneumopatias/imunologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/imunologia , Envelhecimento/imunologia , Envelhecimento/metabolismo
2.
Eur Cell Mater ; 41: 454-470, 2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33881768

RESUMO

Bone healing complications such as delayed healing or non-union affect 5-10 % of patients with a long-bone fracture and lead to reduced quality of life and increased health-care costs. The gut microbiota and the metabolites they produce, mainly short-chain fatty acids (SCFAs), have been shown to impact nearly all organs of the human body including bone. SCFAs show broad activity in positively influencing bone healing outcomes either by acting directly on cell types involved in fracture healing, such as osteoblasts, osteoclasts, chondrocytes and fibroblasts, or indirectly, by shaping an appropriate anti-inflammatory and immune regulatory response. Due to the ability of SCFAs to influence osteoblast and osteoclast differentiation, SCFAs may also affect the integration of orthopaedic implants in bone. In addition, SCFA-derivatives have already been used in a variety of tissue engineering constructs to reduce inflammation and induce bone tissue production. The present review summarises the current knowledge on the role of the gut microbiota, in particular through the action of SCFAs, in the individual stages of bone healing and provides insights into how SCFAs may be utilised in a manner beneficial for fracture healing and surgical reconstruction.


Assuntos
Osso e Ossos/metabolismo , Ácidos Graxos Voláteis/metabolismo , Consolidação da Fratura/fisiologia , Microbioma Gastrointestinal/fisiologia , Animais , Humanos
3.
Ir Med J ; 114(8): 431, 2021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-35863072

RESUMO

Aim NSAIDs are high-risk medicines that can commonly cause adverse renal effects. Recent evidence suggests a rise in the number of patients with acute and chronic renal disease. The aim of this audit is to determine our de-prescribing rate of chronic NSAID use in an Irish general practice. Methods We reviewed NSAID-containing drug prescriptions that were issued over a three month period in 2018. A description analysis was performed to ascertain for the frequency and type of NSAIDs prescribed. An educational session was delivered to clinicians to encourage de-prescribing of NSAIDs if deemed clinically appropriate. Results Fifty-one NSAID-containing prescriptions were identified. Thirty-six (71%) patients, who were prescribed a regular NSAID, were aged between 71-85 years. Meloxicam was used the most (31%), whilst the preferred NSAIDs (naproxen and ibuprofen) were used least (18%). A 37% improvement in de-prescribing of chronic NSAIDs was achieved upon re-auditing. Conclusion NSAIDs are commonly implicated in inappropriate prescribing. Clinicians are encouraged to practice de-prescribing at every opportunity. Recent evidence suggests that pharmacy-led educational interventions can further assist de-prescribing of inappropriate medicines. Thus, a close collaboration between physicians and pharmacists is encouraged to further maximise quality of prescribing and patient care.


Assuntos
Desprescrições , Medicina Geral , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/efeitos adversos , Prescrições de Medicamentos , Humanos , Naproxeno
4.
Diabet Med ; 37(12): 2044-2049, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-30710451

RESUMO

AIMS: The purpose of this study was to identify the number of pregnancies affected by pre-gestational diabetes in the Republic of Ireland; to report on pregnancy outcomes and to identify areas for improvement in care delivery and clinical outcomes. METHODS: Healthcare professionals caring for women with pre-gestational diabetes during pregnancy were invited to participate in this retrospective study. Data pertaining to 185 pregnancies in women attending 15 antenatal centres nationally were collected and analysed. Included pregnancies had an estimated date of delivery between 1 January and 31 December 2015. RESULTS: The cohort consisted of 122 (65.9%) women with Type 1 diabetes and 56 (30.3%) women with Type 2 diabetes. The remaining 7 (3.8%) pregnancies were to women with maturity-onset diabetes of the young (MODY) (n = 6) and post-transplant diabetes (n = 1). Overall women were poorly prepared for pregnancy and lapses in specific areas of service delivery including pre-pregnancy care and retinal screening were identified. The majority of pregnancies 156 (84.3%) resulted in a live birth. A total of 103 (65.5%) women had a caesarean delivery and 58 (36.9%) infants were large for gestational age. CONCLUSIONS: This audit identifies clear areas for improvement in delivery of care for women with diabetes in the Republic of Ireland before and during pregnancy.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/terapia , Cuidado Pré-Concepcional/estatística & dados numéricos , Resultado da Gravidez/epidemiologia , Gravidez em Diabéticas/terapia , Aborto Espontâneo/epidemiologia , Adulto , Aspirina/uso terapêutico , Cesárea , Auditoria Clínica , Atenção à Saúde , Parto Obstétrico , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Retinopatia Diabética/diagnóstico , Feminino , Macrossomia Fetal/epidemiologia , Ácido Fólico/uso terapêutico , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Recém-Nascido , Bombas de Infusão Implantáveis , Insulina/uso terapêutico , Sistemas de Infusão de Insulina , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Irlanda/epidemiologia , Nascido Vivo/epidemiologia , Programas de Rastreamento , Metformina/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Gravidez , Nascimento Prematuro/epidemiologia , Estudos Retrospectivos , Natimorto/epidemiologia , Complexo Vitamínico B/uso terapêutico
5.
Rhinology ; 58(Suppl S29): 1-464, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32077450

RESUMO

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.


Assuntos
Pólipos Nasais , Rinite , Sinusite , Doença Aguda , Adulto , Criança , Doença Crônica , Humanos , Pólipos Nasais/diagnóstico , Pólipos Nasais/terapia , Rinite/diagnóstico , Rinite/terapia , Sinusite/diagnóstico , Sinusite/terapia
6.
Rhinology ; 57(3): 162-168, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30810118

RESUMO

BACKGROUND: The European Position Papers on Rhinosinusitis from 2005, 2007 and 2012 have had a measurable impact on the way this common condition with high impact on quality of life is managed around the world. EPOS2020 will be the latest iteration of the guideline, addressing new stakeholders and target users, presenting a summary of the latest literature and evolving treatment modalities, and formulating clear recommendations based on all available evidence. METHODOLOGY: Based on the AGREE II framework, this article demonstrates how the EPOS2020 steering group will address six key areas to ensure consistency in quality and presentation of information in the latest rhinosinusitis clinical practice guideline: scope and purpose; stakeholder involvement; rigour of development; clarity of presentation; recommendations and applicability; editorial independence. RESULTS: By analysing the guidance from AGREE II, we formulated a detailed development strategy for EPOS2020. We identify new stakeholders and target users and ratify the importance of patient involvement in the latest EPOS guideline. New and expanded areas of research to be addressed are highlighted. We confirm our intention to use mixed methodologies, combining evidence-based medicine with real life studies; when no evidence can be found, use Delphi rounds to achieve clear, inclusive recommendations. We also introduce new concepts for dissemination of the guideline, using Internet and social media to improve accessibility. CONCLUSION: This article is an introduction to the EPOS2020 project, and presents the key goals, core stakeholders, planned methodology and dissemination strategies for the latest version of this influential guideline.


Assuntos
Objetivos , Qualidade de Vida , Rinite , Sinusite , Medicina Baseada em Evidências , Humanos , Participação do Paciente , Rinite/terapia , Sinusite/terapia
7.
Ir Med J ; 112(5): 932, 2019 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-31411014

RESUMO

Aim Proton pump inhibitors (PPIs) are amongst the most frequently prescribed medicines. Evidence to date shows these are being inappropriately overprescribed. Although highly effective, PPIs are increasingly recognized to be associated with many adverse health outcomes. The aims of this study are to assess the extent and quality of PPI prescribing in an urban general practice. Method Retrospective chart review and descriptive analysis of all prescriptions issued over one month was undertaken to determine the frequency and duration of PPI use, the likely indications and results of endoscopic findings. Results PPIs represented 20% of all prescriptions issued in June 2017, of which 80% were on long-term therapy. Esomeprazole use prevailed. Low dose therapy was least frequently prescribed (7%) compared with high dose therapy (93%). PPI use increased with age, and duration of therapy was prolonged for greater than one year in the majority of patients. Patients were commenced therapy without clear indication in 40% of cases. Findings of endoscopic evaluation in 58 (64%) patients suggest PPI therapy was inappropriately continued in the majority of cases (81%). Conclusion Chronic inappropriate overprescribing of PPIs remains a concern and contribute potentially to patient harm and wasteful financial resources. The ongoing need to optimise PPI prescribing remains paramount. Clinicians are encouraged to prescribe judiciously and in accordance with evidence-based guidelines.


Assuntos
Medicina Geral/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Inibidores da Bomba de Prótons/uso terapêutico , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Endoscopia Gastrointestinal/estatística & dados numéricos , Feminino , Humanos , Prescrição Inadequada/estatística & dados numéricos , Irlanda , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/administração & dosagem , Estudos Retrospectivos , Adulto Jovem
8.
Allergy ; 73(4): 837-850, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29069535

RESUMO

Innate lymphoid cells (ILC) represent a group of lymphocytes that lack specific antigen receptors and are relatively rare as compared to adaptive lymphocytes. ILCs play important roles in allergic and nonallergic inflammatory diseases due to their location at barrier surfaces within the airways, gut, and skin, and they respond to cytokines produced by activated cells in their local environment. Innate lymphoid cells contribute to the immune response by the release of cytokines and other mediators, forming a link between innate and adaptive immunity. In recent years, these cells have been extensively characterized and their role in animal models of disease has been investigated. Data to translate the relevance of ILCs in human pathology, and the potential role of ILCs in diagnosis, as biomarkers and/or as future treatment targets are also emerging. This review, produced by a task force of the Immunology Section of the European Academy of Allergy and Clinical Immunology (EAACI), encompassing clinicians and researchers, highlights the role of ILCs in human allergic and nonallergic diseases in the airways, gastrointestinal tract, and skin, with a focus on new insights into clinical implications, therapeutic options, and future research opportunities.


Assuntos
Hipersensibilidade/imunologia , Imunidade Inata/imunologia , Inflamação/imunologia , Linfócitos/imunologia , Animais , Humanos
9.
Allergy ; 73(2): 328-340, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28921585

RESUMO

While desired for the cure of allergy, regulatory immune cell subsets and nonclassical Th2-biased inflammatory mediators in the tumour microenvironment can contribute to immune suppression and escape of tumours from immunological detection and clearance. A key aim in the cancer field is therefore to design interventions that can break immunological tolerance and halt cancer progression, whereas on the contrary allergen immunotherapy exactly aims to induce tolerance. In this position paper, we review insights on immune tolerance derived from allergy and from cancer inflammation, focusing on what is known about the roles of key immune cells and mediators. We propose that research in the field of AllergoOncology that aims to delineate these immunological mechanisms with juxtaposed clinical consequences in allergy and cancer may point to novel avenues for therapeutic interventions that stand to benefit both disciplines.


Assuntos
Hipersensibilidade/imunologia , Hipersensibilidade/terapia , Tolerância Imunológica/imunologia , Imunoterapia/métodos , Neoplasias/imunologia , Neoplasias/terapia , Dessensibilização Imunológica/métodos , Humanos
10.
Allergy ; 73(4): 799-815, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29205393

RESUMO

Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA-AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE-mediated Food Allergy, aims to provide evidence-based recommendations for active treatment of IgE-mediated food allergy with FA-AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post-discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA-AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post-discontinuation is also suggested, but not confirmed. Adverse events during FA-AIT have been frequently reported, but few subjects discontinue FA-AIT as a result of these. Taking into account the current evidence, FA-AIT should only be performed in research centers or in clinical centers with an extensive experience in FA-AIT. Patients and their families should be provided with information about the use of FA-AIT for IgE-mediated food allergy to allow them to make an informed decision about the therapy.


Assuntos
Dessensibilização Imunológica/métodos , Dessensibilização Imunológica/normas , Hipersensibilidade Alimentar/prevenção & controle , Animais , Humanos , Imunoglobulina E/imunologia
11.
Clin Exp Allergy ; 47(11): 1398-1408, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28618148

RESUMO

BACKGROUND: Recently, the nature of the lipid-ligand of Pru p 3, one of the most common plant food allergens in southern Europe, has been identified as a derivative of the alkaloid camptothecin bound to phytosphingosine. However, the origin of its immunological activity is still unknown. OBJECTIVE: We sought to evaluate the role of the Pru p 3 lipid-ligand in the immunogenic activity of Pru p 3. METHODS: In vitro cultures of different cell types (monocyte-derived dendritic cells [moDCs], PBMCs [peripheral blood mononuclear cells] and epithelial and iNKT-hybridoma cell lines) have been used to determine the immunological capacity of the ligand, by measuring cell proliferation, maturation markers and cytokine production. To study the capacity of the lipid-ligand to promote sensitization to Pru p 3 in vivo, a mouse model of anaphylaxis to peach has been produced and changes in the humoral and basophil responses have been analysed. RESULTS: The lipid-ligand of Pru p 3 induced maturation of moDCsc and proliferation of PBMCs. Its immunological activity resided in the phytosphingosine tail of the ligand. The adjuvant activity of the ligand was also confirmed in vivo, where the complex of Pru p 3-ligand induced higher levels of IgE than Pru p 3 alone. The immunological capacity of the Pru p 3 ligand was mediated by CD1d, as maturation of moDCs was inhibited by anti-CD1d antibodies and Pru p 3-ligand co-localized with CD1d on epithelial cells. Finally, Pru p 3-ligand presented by CD1d was able to interact with iNKTs. CONCLUSIONS AND CLINICAL RELEVANCE: The Pru p 3 lipid-ligand could act as an adjuvant to promote sensitization to Pru p 3, through its recognition by CD1d receptors. This intrinsic adjuvant activity of the accompanying lipid cargo could be a general essential feature of the mechanism underlying the phenomenon of allergenicity.


Assuntos
Antígenos de Plantas/imunologia , Hipersensibilidade Alimentar/imunologia , Proteínas de Plantas/imunologia , Sequência de Aminoácidos , Animais , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/metabolismo , Antígenos CD1d/imunologia , Antígenos CD1d/metabolismo , Antígenos de Plantas/administração & dosagem , Antígenos de Plantas/química , Citocinas/metabolismo , Europa (Continente) , Imunização , Imunoglobulina E/imunologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Ligantes , Lipídeos/imunologia , Ativação Linfocitária/imunologia , Camundongos , Modelos Moleculares , Células T Matadoras Naturais/imunologia , Células T Matadoras Naturais/metabolismo , Proteínas de Plantas/administração & dosagem , Proteínas de Plantas/química , Ligação Proteica , Conformação Proteica , Linfócitos T/imunologia , Linfócitos T/metabolismo
12.
Allergy ; 72(12): 1925-1935, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28618071

RESUMO

BACKGROUND: Histamine is a key immunoregulatory mediator and can dampen proinflammatory responses via activation of histamine receptor 2 (H2 R). The aim of this study was to determine the role of H2 R in modulating lung inflammatory responses. METHODS: H2 R was blocked using famotidine or activated using dimaprit in both the ovalbumin (OVA) and house dust mite extract (HDM) murine models of respiratory inflammation. H2 R-deficient animals and CD1d/H2 R-deficient animals were utilized to examine the CD1d presentation of lipid antigens (αGalCer or OCH) to invariant natural killer T (iNKT) cells. RESULTS: Famotidine treatment resulted in more severe airway disease in the OVA model, while dimaprit treatment significantly reduced disease severity. Both OVA and HDM-induced airway diseases were more severe in H2 R-deficient animals. Flow cytometric analysis of lung tissue from H2 R-deficient animals revealed increased numbers of CD1d+ dendritic cells and increased numbers of iNKT cells. In vitro, αGalCer-stimulated iNKT cells from H2 R-deficient mice secreted higher levels of IL-4, IL-5, and GM-CSF. In vivo, αGalCer or OCH administration to the lung resulted in enhanced mucus secretion, inflammatory cell recruitment, and cytokine production in H2 R-deficient or famotidine-treated animals, while dimaprit dampened the lung iNKT cell response to αGalCer. Removal of iNKT cells in H2 R-deficient (CD1d-/- H2 R-/- ) animals normalized the lung response to HDM. CONCLUSION: The deliberate activation of H2 R, or its downstream signaling molecules, may represent a novel therapeutic target for chronic lung inflammatory diseases, especially when CD1d-mediated presentation of lipid antigens to iNKT cells is contributing to the pathology.


Assuntos
Células T Matadoras Naturais/imunologia , Células T Matadoras Naturais/metabolismo , Pneumonia/imunologia , Pneumonia/metabolismo , Receptores Histamínicos H2/metabolismo , Animais , Antígenos CD1d/metabolismo , Biomarcadores , Modelos Animais de Doenças , Progressão da Doença , Feminino , Imunofenotipagem , Mediadores da Inflamação , Ativação Linfocitária/imunologia , Contagem de Linfócitos , Camundongos , Camundongos Knockout , Fenótipo , Pneumonia/genética , Pneumonia/patologia , Receptores Histamínicos H2/genética , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo
13.
Allergy ; 72(11): 1744-1752, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28397284

RESUMO

BACKGROUND: Fatty acids and lipid mediator signaling play an important role in the pathogenesis of asthma, yet this area remains largely underexplored. The aims of this study were (i) to examine fatty acid levels and their metabolism in obese and nonobese asthma patients and (ii) to determine the functional effects of altered fatty acid metabolism in experimental models. METHODS: Medium- and long-chain fatty acid levels were quantified in serum from 161 human volunteers by LC/MS. Changes in stearoyl-coenzyme A desaturase (SCD) expression and activity were evaluated in the ovalbumin (OVA) and house dust mite (HDM) murine models. Primary human bronchial epithelial cells from asthma patients and controls were evaluated for SCD expression and activity. RESULTS: The serum desaturation index (an indirect measure of SCD) was significantly reduced in nonobese asthma patients and in the OVA murine model. SCD1 gene expression was significantly reduced within the lungs following OVA or HDM challenge. Inhibition of SCD in mice promoted airway hyper-responsiveness. SCD1 expression was suppressed in bronchial epithelial cells from asthma patients. IL-4 and IL-13 reduced epithelial cell SCD1 expression. Inhibition of SCD reduced surfactant protein C expression and suppressed rhinovirus-induced IP-10 secretion, which was associated with increased viral titers. CONCLUSIONS: This is the first study to demonstrate decreased fatty acid desaturase activity in humans with asthma. Experimental models in mice and human epithelial cells suggest that inhibition of desaturase activity leads to airway hyper-responsiveness and reduced antiviral defense. SCD may represent a new target for therapeutic intervention in asthma patients.


Assuntos
Asma/metabolismo , Ácidos Graxos/metabolismo , Estearoil-CoA Dessaturase/metabolismo , Animais , Asma/enzimologia , Brônquios/citologia , Células Cultivadas , Células Epiteliais/enzimologia , Ácidos Graxos/sangue , Humanos , Metabolismo dos Lipídeos , Camundongos , Obesidade , Hipersensibilidade Respiratória/enzimologia
14.
Allergy ; 72(8): 1133-1147, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28058751

RESUMO

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT in the management of food allergy. METHODS: We undertook a systematic review and meta-analysis that involved searching nine international electronic databases for randomized controlled trials (RCTs) and nonrandomized studies (NRS). Eligible studies were independently assessed by two reviewers against predefined eligibility criteria. The quality of studies was assessed using the Cochrane Risk of Bias tool for RCTs and the Cochrane ACROBAT-NRS tool for quasi-RCTs. Random-effects meta-analyses were undertaken, with planned subgroup and sensitivity analyses. RESULTS: We identified 1814 potentially relevant papers from which we selected 31 eligible studies, comprising of 25 RCTs and six NRS, studying a total of 1259 patients. Twenty-five trials evaluated oral immunotherapy (OIT), five studies investigated sublingual immunotherapy, and one study evaluated epicutaneous immunotherapy. The majority of these studies were in children. Twenty-seven studies assessed desensitization, and eight studies investigated sustained unresponsiveness postdiscontinuation of AIT. Meta-analyses demonstrated a substantial benefit in terms of desensitization (risk ratio (RR) = 0.16, 95% CI 0.10, 0.26) and suggested, but did not confirm sustained unresponsiveness (RR = 0.29, 95% CI 0.08, 1.13). Only one study reported on disease-specific quality of life (QoL), which reported no comparative results between OIT and control group. Meta-analyses revealed that the risk of experiencing a systemic adverse reaction was higher in those receiving AIT, with a more marked increase in the risk of local adverse reactions. Sensitivity analysis excluding those studies judged to be at high risk of bias demonstrated the robustness of summary estimates of effectiveness and safety of AIT for food allergy. None of the studies reported data on health economic analyses. CONCLUSIONS: AIT may be effective in raising the threshold of reactivity to a range of foods in children with IgE-mediated food allergy whilst receiving (i.e. desensitization) and post-discontinuation of AIT. It is, however, associated with a modest increased risk in serious systemic adverse reactions and a substantial increase in minor local adverse reactions. More data are needed in relation to adults, long term effects, the impact on QoL and the cost-effectiveness of AIT.


Assuntos
Alérgenos/imunologia , Dessensibilização Imunológica , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/terapia , Alimentos/efeitos adversos , Imunoglobulina E/imunologia , Alérgenos/administração & dosagem , Animais , Dessensibilização Imunológica/métodos , Humanos , Razão de Chances , Qualidade de Vida , Imunoterapia Sublingual , Resultado do Tratamento
15.
Eur Cell Mater ; 34: 321-340, 2017 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-29160896

RESUMO

Fracture-related infection (FRI) is a major complication in surgically fixed fractures. Instability of the fracture after fixation is considered a risk factor for infection; however, few experimental data are available confirming this belief. To study whether stable fractures led to higher infection clearance, mouse femoral osteotomies were fixed with either stable or unstable fixation and the surgical site was contaminated with either Staphylococcus epidermidis (S. epidermidis)or Staphylococcus aureus (S. aureus)clinical isolates. Infection progression was assessed at different time points by quantitative bacteriology, total cell counts in spleen and lymph node and histological analysis. Operated, non-inoculated mice were used as controls. Two inbred mouse strains (C57BL/6 and BALB/c) were included in the study to determine the influence of different host background in the outcome. Stable fixation allowed a higher proportion of C57BL/6 mice to clear S. epidermidis inoculation in comparison to unstable fixation. No difference associated with fixation type was observed for BALB/c mice. Inoculation with S. aureus resulted in a more severe infection for both stable and unstable fractures in both mouse strains; however, significant osteolysis around the screws rendered the stable group functionally unstable. Our results suggested that fracture stability could have an influence on S. epidermidis infection, although host factors also played a role. No differences were observed when using S. aureus, due to a more severe infection, leading to osteolysis and loss of stability in both groups. Further studies are required in order to address the biological features underlying the differences observed.


Assuntos
Fraturas do Fêmur/cirurgia , Fixação de Fratura/métodos , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus epidermidis/crescimento & desenvolvimento , Animais , Carga Bacteriana , Biofilmes/crescimento & desenvolvimento , Feminino , Fraturas do Fêmur/microbiologia , Fixação de Fratura/efeitos adversos , Fixação de Fratura/instrumentação , Interações Hospedeiro-Patógeno , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Varredura , Osteólise/microbiologia , Especificidade da Espécie , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/fisiologia , Staphylococcus aureus/ultraestrutura , Staphylococcus epidermidis/fisiologia , Staphylococcus epidermidis/ultraestrutura , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/microbiologia
16.
Allergy ; 69(3): 273-81, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24286351

RESUMO

Histamine is a biogenic amine with extensive effects on many cell types, mediated by the activation of its four receptors (H1R-H4R). Distinct effects are dependent on receptor subtypes and their differential expression. Within the gastrointestinal tract, histamine is present at relatively high concentrations, particularly during inflammatory responses. In this review, we discuss the immunoregulatory influence of histamine on a number of gastrointestinal disorders, including food allergy, scombroid food poisoning, histamine intolerance, irritable bowel syndrome, and inflammatory bowel disease. It is clear that the effects of histamine on mucosal immune homeostasis are dependent on expression and activity of the four currently known histamine receptors; however, the relative protective or pathogenic effects of histamine on inflammatory processes within the gut are still poorly defined and require further investigation.


Assuntos
Trato Gastrointestinal/imunologia , Trato Gastrointestinal/metabolismo , Histamina/metabolismo , Mucosa/imunologia , Mucosa/metabolismo , Animais , Trato Gastrointestinal/microbiologia , Humanos , Imunidade nas Mucosas , Imunomodulação , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/microbiologia , Mucosa/microbiologia
17.
Allergy ; 69(5): 590-601, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24697491

RESUMO

Food allergy can have significant effects on morbidity and quality of life and can be costly in terms of medical visits and treatments. There is therefore considerable interest in generating efficient approaches that may reduce the risk of developing food allergy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Prevention and is part of the EAACI Guidelines for Food Allergy and Anaphylaxis. It aims to provide evidence-based recommendations for primary prevention of food allergy. A wide range of antenatal, perinatal, neonatal, and childhood strategies were identified and their effectiveness assessed and synthesized in a systematic review. Based on this evidence, families can be provided with evidence-based advice about preventing food allergy, particularly for infants at high risk for development of allergic disease. The advice for all mothers includes a normal diet without restrictions during pregnancy and lactation. For all infants, exclusive breastfeeding is recommended for at least first 4-6 months of life. If breastfeeding is insufficient or not possible, infants at high-risk can be recommended a hypoallergenic formula with a documented preventive effect for the first 4 months. There is no need to avoid introducing complementary foods beyond 4 months, and currently, the evidence does not justify recommendations about either withholding or encouraging exposure to potentially allergenic foods after 4 months once weaning has commenced, irrespective of atopic heredity. There is no evidence to support the use of prebiotics or probiotics for food allergy prevention.


Assuntos
Anafilaxia/prevenção & controle , Hipersensibilidade Alimentar/prevenção & controle , Prevenção Primária , Adulto , Aleitamento Materno , Criança , Pré-Escolar , Suplementos Nutricionais , Feminino , Humanos , Lactente , Fórmulas Infantis , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Masculino , Gravidez
18.
Allergy ; 69(5): 581-9, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24433563

RESUMO

BACKGROUND: Food allergies can have serious physical, social, and financial consequences. This systematic review examined ways to prevent the development of food allergy in children and adults. METHODS: Seven bibliographic databases were searched from their inception to September 30, 2012, for systematic reviews, randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, controlled before-and-after studies, interrupted time series studies, and prospective cohort studies. Experts were consulted for additional studies. There were no language or geographic restrictions. Two reviewers appraised the studies using appropriate tools. Data were not suitable for meta-analysis due to heterogeneity, so were narratively synthesized. RESULTS: Seventy-four studies were included, one-third of which were of high quality. There was no good evidence to recommend that pregnant or breastfeeding women should change their diet or take supplements to prevent allergies in infants at high or normal risk. There were mixed findings about the preventive benefits of breastfeeding for infants at high or normal risk, but there was evidence to recommend avoiding cow's milk and substituting with extensively or partially hydrolyzed whey or casein formulas for infants at high risk for the first 4 months. Soy milk and delaying the introduction of solid foods beyond 4 months did not have preventive benefits in those at high or normal risk. There was very little evidence about strategies for preventing food allergy in older children or adults. CONCLUSIONS: There is much to learn about preventing food allergy, and this is a priority given the high societal and healthcare costs involved.


Assuntos
Hipersensibilidade Alimentar/prevenção & controle , Prevenção Primária , Adulto , Aleitamento Materno , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Fórmulas Infantis , Recém-Nascido , Masculino , Gravidez
19.
Cell Immunol ; 281(2): 134-40, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23648818

RESUMO

The outcome following infection depends on the generation of an immune response that results in control of the pathogenic microorganism, while limiting inflammatory collateral damage to the host. Bifidobacterium infantis 35624 was shown to be protective against Salmonella associated host injury via a Treg-dependent mechanism. In this study, we further examined the mechanisms by which B. infantis-induced Tregs protect against Salmonella-associated inflammation. B. infantis 35624 feeding to Salmonella-infected mice significantly reduced Peyer's patch MIP-1α and MIP-1ß secretion. Chemokine secretion was significantly inversely correlated with Peyer's patch CD4+CD25+ cell numbers. In vitro, CD25+ T cells, but not CD25- T cells, specifically inhibited TNF-α and IFN-γ secretion. However, both CD25+ and CD25- T cells suppressed MIP-1α and MIP-1ß secretion to the same extent. This study suggests that although B. infantis 35624-induced Tregs correlate with inhibition of chemokine secretion within the mucosa of pathogen infected animals, indirect cellular mechanisms may play a role.


Assuntos
Bifidobacterium/imunologia , Linfócitos T CD4-Positivos/imunologia , Quimiocina CCL3/imunologia , Quimiocina CCL4/imunologia , Nódulos Linfáticos Agregados/imunologia , Salmonelose Animal/imunologia , Animais , Bifidobacterium/fisiologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Células Cultivadas , Quimiocina CCL3/metabolismo , Quimiocina CCL4/metabolismo , Técnicas de Cocultura , Citometria de Fluxo , Interações Hospedeiro-Patógeno/imunologia , Interferon gama/imunologia , Interferon gama/metabolismo , Subunidade alfa de Receptor de Interleucina-2/imunologia , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Contagem de Linfócitos , Camundongos , Camundongos Endogâmicos BALB C , Nódulos Linfáticos Agregados/metabolismo , Nódulos Linfáticos Agregados/microbiologia , Salmonelose Animal/microbiologia , Salmonella typhimurium/imunologia , Salmonella typhimurium/fisiologia , Baço/imunologia , Baço/metabolismo , Baço/patologia , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo
20.
Clin Exp Allergy ; 43(12): 1374-83, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24261947

RESUMO

BACKGROUND: Since intestinal absorption of food protein can trigger an allergic reaction, the effect of plant food allergen on intestinal epithelial cell permeability and its ability to cross the epithelial monolayer was evaluated. OBJECTIVE: To study the interaction of Pru p 3 with intestinal epithelium, its natural entrance, analyzing transport kinetics and cellular responses that trigger. METHODS: This was achieved using Pru p 3, the peach LTP, as a model. Enterocytic monolayers were established by culturing Caco 2 cells, as a model of enterocytes, on permeable supports that separate the apical and basal compartments. Pru p 3 was added to the apical compartment, the transepithelial resistance (TEER) was measured, and the transport was quantified. RESULTS: The peach allergen that crossed the cell monolayer was detected in the cell fraction and in the basal medium by immunodetection with specific antibodies and the quantity was measured by ELISA assay. Pru p 3 was able to cross the monolayer without disturbing the integrity of the tight junctions. This transport was significantly higher than that of a non-allergenic peach LTP, LTP1, and occurred via lipid raft pathway. The incubation of Caco 2 cells with Pru p 3 and LTP1 produced the expression of epithelial-specific cytokines TSLP, IL33 and IL25. CONCLUSION: These results suggest that Pru p 3 was able to cross the cell monolayer by the transcellular route and then induce the production of Th2 cytokines. The results of the present study represent a step towards clarifying the importance of Pru p 3 as a sensitizer. CLINICAL RELEVANCE: The capacity of food allergens to cross the intestinal monolayer could explain their high allergenic capacity and its fast diffusion through the body associating to severe symptoms.


Assuntos
Antígenos de Plantas/imunologia , Antígenos de Plantas/metabolismo , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Proteínas de Plantas/imunologia , Proteínas de Plantas/metabolismo , Transporte Biológico , Linhagem Celular , Citocinas/biossíntese , Hipersensibilidade Alimentar/genética , Humanos , Imunoglobulina E/imunologia , Imunoglobulina E/metabolismo , Cinética , Ligação Proteica/imunologia , Transporte Proteico , Proteólise , Células Th2/imunologia , Células Th2/metabolismo , Vesículas Transportadoras/metabolismo
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