Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.461
Filtrar
1.
Rev Med Liege ; 76(3): 202-207, 2021 Mar.
Artigo em Francês | MEDLINE | ID: mdl-33682390

RESUMO

In cystic fibrosis, lung disease is early and insidious. It almost always conditions the prognosis. A pragmatic way of looking at prognostic factors is to distinguish those on which care management has little (environmental factors) or no grip (genetic factors) and those related to the quality of care, the latter being crucial. Recently, a triple-combination CFTR («Cystic Fibrosis Transmembrane conductance Regulator¼) modulator regimen has been shown a highly effective therapy. Ultimately, at least 90 % of Belgian patients with cystic fibrosis should benefit from this drug. However, its official price is extremely high (712 €/day), lacks transparency and illustrates problematic aspects of current orphan legislations. For the majority of citizens in Western Europe, a social ideal still prevails that healthcare should be accessible to all in an equitable fashion. Somewhere between this price and the necessity for national health systems based on solidarity to keep the costs of orphan drugs at a sustainable level, patients are looking like hostages.


Assuntos
Fibrose Cística , Quinolonas , Aminofenóis , Aminopiridinas , Benzodioxóis , Fibrose Cística/diagnóstico , Fibrose Cística/terapia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Europa (Continente) , Humanos , Mutação , Prognóstico
2.
Arch. argent. pediatr ; 119(1): S17-S35, feb. 2021. tab, ilus
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1147358

RESUMO

La presente revisión de la "Guía de diagnóstico y tratamiento de pacientes con fibrosis quística"publicada en el año 2014 tiene como objetivo actualizar el conocimiento acerca de varios aspectos relacionados con el manejo clínico de la enfermedad, según los avances científicos publicados y en desarrollo en los últimos años. Solo se tratarán aquí tópicos nuevos y aquellos que, a la luz de la investigación, requieren ser modificados, por lo que el contenido de la anterior guía permanece vigente en el resto de las cuestiones.Los aspectos actualizados se dan en el diagnóstico de la enfermedad por los cambios realizados en el test del sudor, la pesquisa neonatal y la biología molecular, la actualización de estudios de seguimiento, como el índice de aclaramiento pulmonar y la resonancia magnética nuclear, y modificaciones con respecto al área nutricional (diabetes secundaria a fibrosis quística) y el tratamiento kinésico y de rehabilitación pulmonar


The present revision of the Guide for the diagnosis and treatment of patients with cystic fibrosis published in 2014 aims to update the knowledge about various aspects related to the clinical management of the disease, according to the scientific advances published and in development in recent years. Only new topics will be discussed here and those that, in light of the research, require modification, so the content of the previous guide remains valid in the rest of the aspects.The updated aspects range over the diagnosis of the disease due to the changes made in the sweat test, the neonatal screening and molecular biology, the update of follow-up studies, such as the Lung Clearance Index and the Nuclear Magnetic Resonance, and modifications regarding the nutritional area (diabetes secondary to cystic fibrosis) and the physiotherapy treatment and pulmonary rehabilitation.


Assuntos
Humanos , Criança , Fibrose Cística/diagnóstico , Fibrose Cística/terapia , Infecções Respiratórias/terapia
3.
Arch Biochem Biophys ; 699: 108763, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33460581

RESUMO

MicroRNAs (miRNAs) are small non-coding highly conserved RNA molecules that can act as master regulators of gene expression in a sequence-specific manner either by translation repression or mRNA degradation, influencing a wide range of biologic processes that are essential for the maintenance of cellular homeostasis. Chronic pediatric diseases are the leading cause of death worldwide among children and the recent evidence indicates that aberrant miRNA expression significantly contributes to the development of chronic pediatric diseases. This review focuses on the role of miRNAs in five major chronic pediatric diseases including bronchial asthma, congenital heart diseases, cystic fibrosis, type 1 diabetes mellitus, and epilepsy, and their potential use as novel biomarkers for the diagnosis and prognosis of these disorders.


Assuntos
Asma/fisiopatologia , Fibrose Cística/fisiopatologia , Diabetes Mellitus Tipo 1/fisiopatologia , Epilepsia/fisiopatologia , Cardiopatias Congênitas/fisiopatologia , MicroRNAs/fisiologia , Asma/diagnóstico , Asma/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Doença Crônica , Fibrose Cística/diagnóstico , Fibrose Cística/metabolismo , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/metabolismo , Epilepsia/diagnóstico , Epilepsia/metabolismo , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/metabolismo , Humanos , MicroRNAs/sangue , MicroRNAs/metabolismo , Pediatria , Prognóstico
4.
Ital J Pediatr ; 47(1): 2, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407736

RESUMO

BACKGROUND: Cystic fibrosis (CF) is a life-threatening disease affecting about 1:3000 newborns in Caucasian populations. The introduction of newborn screening for cystic fibrosis (CF NBS) has improved the clinical outcomes of individuals with CF through early diagnosis and early treatment. NBS strategies have been implemented over time. CF NBS was introduced extensively in 1984 in Tuscany, a region with 3.7 million people, characterized by a high allelic heterogeneity of CFTR gene. AIM AND METHODS: The aim of the study is to present the results from 34 years (1984-2018) of CF NBS, retrospectively evaluating the sensitivity, specificity and predictive values of the tests. In particular, we studied the impact of the introduction of DNA molecular analysis in NBS in a region with high allelic heterogeneity, such as Tuscany. RESULTS: Over these 34 years, 919,520 neonates were screened, using four different NBS strategies. From 1984 to 1991, CF NBS was performed by the determination of albumin on dried meconium (sensitivity 68.75%; specificity 99.82%). Subsequently, the analysis of immunoreactive trypsinogen on a blood spot was adopted as CF NBS protocol (sensitivity 83.33%; specificity 99.77%). From 1992 to 2010, this strategy was associated with lactase meconium dosage: IRT1/IRT2 + LACT protocol (sensitivity 87.50%; specificity 99.82%). From 2011, when the existing algorithm was integrated by analysis of CF causing variants of the CFTR gene (IRT1/IRT2 + LACT + IRT1/DNA protocol), a substantial improvement in sensitivity was seen (senisitivity 96.15%; specificity 99.75%). Other improved parameters with DNA analysis in the NBS programme, compared with the previous method, were the diagnosis time (52 days vs. 38 days) and the recall rate (0.58 to 0.38%). CONCLUSION: The inclusion of DNA analysis in the NBS was a fundamental step in improving sensitivity, even in a region with high allelic variability.


Assuntos
Fibrose Cística/diagnóstico , Fibrose Cística/epidemiologia , Triagem Neonatal , Feminino , Testes Genéticos , Humanos , Recém-Nascido , Itália , Masculino , Estudos Retrospectivos , Sensibilidade e Especificidade
5.
Am J Hum Genet ; 108(1): 8-15, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33417889

RESUMO

The delineation of disease entities is complex, yet recent advances in the molecular characterization of diseases provide opportunities to designate diseases in a biologically valid manner. Here, we have formalized an approach to the delineation of Mendelian genetic disorders that encompasses two distinct but inter-related concepts: (1) the gene that is mutated and (2) the phenotypic descriptor, preferably a recognizably distinct phenotype. We assert that only by a combinatorial or dyadic approach taking both of these attributes into account can a unitary, distinct genetic disorder be designated. We propose that all Mendelian disorders should be designated as "GENE-related phenotype descriptor" (e.g., "CFTR-related cystic fibrosis"). This approach to delineating and naming disorders reconciles the complexity of gene-to-phenotype relationships in a simple and clear manner yet communicates the complexity and nuance of these relationships.


Assuntos
Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/genética , Genômica/métodos , Fibrose Cística/diagnóstico , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Genótipo , Humanos , Mutação/genética , Fenótipo
6.
BMJ Open ; 10(12): e044755, 2020 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-33310815

RESUMO

OBJECTIVE: To explore current communication practices for positive newborn screening results from the newborn bloodspot screening (NBS) laboratory to clinicians to highlight differences, understand how the pathways are implemented in practice, identify barriers and facilitators and make recommendations for future practice and research. DESIGN: A qualitative exploratory design was employed using semi-structured interviews. SETTING: Thirteen NBS laboratories in England. PARTICIPANTS: Seventy-one clinicians; 22 NBS laboratory staff across 13 laboratories and 49 members of relevant clinical teams were interviewed. RESULTS: Assurance of quality and consistency was a priority for all NBS laboratories. Findings indicated variation in approaches to communicating positive NBS results from laboratories to clinical teams. This was particularly evident for congenital hypothyroidism and was largely influenced by local arrangements, resources and the fact individual laboratories had detailed standard operating procedures for how they work. Obtaining feedback from clinical teams to the laboratory after the child had been seen could be challenging and time-consuming for those involved. Pathways for communicating carrier results for cystic fibrosis and sickle cell disease could be ambiguous and inconsistent which in turn could hamper the laboratories efforts to obtain timely feedback regarding whether or not the result had been communicated to the family. Communication pathways for positive NBS results between laboratories and clinical teams could therefore be time-consuming and resource-intensive. CONCLUSION: The importance placed on ensuring positive NBS results were communicated effectively and in a timely fashion from the laboratory to the clinical team was evident from all participants. However, variation existed in terms of the processes used to report positive NBS results to clinical teams and the people involved. Variant practice identified may reflect local needs, but more often reflected local resources and a more consistent 'best practice' approach is required, not just in the UK but perhaps globally. TRIAL REGISTRATION NUMBER: ISRCTN15330120.


Assuntos
Anemia Falciforme , Fibrose Cística , Triagem Neonatal , Anemia Falciforme/diagnóstico , Comunicação , Fibrose Cística/diagnóstico , Inglaterra , Estudos de Avaliação como Assunto , Humanos , Recém-Nascido
7.
Rev Esp Salud Publica ; 942020 Dec 16.
Artigo em Espanhol | MEDLINE | ID: mdl-33323921

RESUMO

Faced with the prospect of a collapsed health system due to the COVID-19 pandemic, the professionals involved in the Neonatal Screening Programme (NSP) of Catalonia had to adapt to this situation in a flexible, forceful and efficient manner. The most important goals were to prevent the risk of infection in the professionals, in families and their newborns, as well as to ensure the same effectiveness for the early detection of the diseases included in our programme. To this end, the laboratory was reorganised by dividing the staff into groups and the spaces were redistributed. It was also necessary to modify several protocols and circuits, especially for the management of early discharges from maternity centres, and for the collection of the necessary second samples (from newborns with inconclusive results or for low quality samples). In general, a 36% reduction in the time of arrival of these second samples at the laboratory was achieved with respect to the previous circuit. In the specific case of cystic fibrosis detection, the implementation of a new strategy meant a 100% reduction in the request for second samples and a 70% reduction in the age of diagnosis of the newborn. After evaluating these changes, it can be concluded that in the face of the pandemic, the NSP of Catalonia showed determined leadership, aligning all its professionals, ensuring the continuity of the activity in the programme and generating new opportunities. The new processes and circuits implemented have been definitively consolidated, improving the efficiency of the programme.


Assuntos
/epidemiologia , Fibrose Cística/diagnóstico , Triagem Neonatal/métodos , Triagem Neonatal/tendências , Feminino , Humanos , Recém-Nascido , Laboratórios , Liderança , Pandemias , Gravidez , Risco , Espanha/epidemiologia
8.
Ital J Pediatr ; 46(1): 143, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023602

RESUMO

The Veneto region is one of the most affected Italian regions by COVID-19. Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), may constitute a risk factor in COVID-19. Moreover, respiratory viruses were generally associated with severe pulmonary impairment in cystic fibrosis (CF). We would have therefore expected numerous cases of severe COVID-19 among the CF population. Surprisingly, we found that CF patients were significantly protected against infection by SARS-CoV-2. We discussed this aspect formulating some reasonable theories.


Assuntos
Infecções por Coronavirus/epidemiologia , Fibrose Cística/epidemiologia , Pandemias/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Adulto , Técnicas de Laboratório Clínico/métodos , Estudos de Coortes , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Fibrose Cística/diagnóstico , Feminino , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Valores de Referência , Estudos Retrospectivos , Medição de Risco
9.
Acta Biomed ; 91(3): e2020035, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32921729

RESUMO

The novel coronavirus SARS-CoV-2 was first identified in China in December 2019 and has since spread worldwide. People with Cystic Fibrosis (CF) have reduced survival mainly because of respiratory failure due to chronic pulmonary infections. Therefore, CF patients should be considered to have an increased risk of developing severe manifestations in case of SARS-CoV-2 infection. Surprisingly, the results of recent studies concerning SARS-CoV-2 infection in patients with CF show that in these patients the infection rate was lower than that of the general population. Various factors have been considered to explain a possible protective effect of CF against SARS-CoV-2 infection.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Fibrose Cística/epidemiologia , Pulmão/diagnóstico por imagem , Pandemias , Pneumonia Viral/epidemiologia , Tomografia Computadorizada por Raios X/métodos , Comorbidade , Fibrose Cística/diagnóstico , Humanos
10.
Pediatrics ; 146(4)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32978295

RESUMO

Although infants with meconium ileus usually present with apparent symptoms shortly after birth, the diagnosis of meconium ileus and cystic fibrosis (CF) may be delayed, awaiting newborn screening (NBS) results. We present the case of an 11-day-old term girl with delayed passage of meconium at 48 hours who had 2 subsequent small meconium stools over the following week. There was a normal feeding history and no signs of abdominal distension or distress. She then presented with an acute abdomen, decompensated shock, bowel perforation, and peritonitis, requiring multiple intestinal surgeries. Her NBS for CF was positive, and CF was ultimately confirmed with mutation analysis. Her course was complicated by prolonged parenteral feedings and mechanical ventilation via tracheostomy. The infant was managed with soy oil, medium chain triglycerides, olive oil, fish oil lipids and experienced only transaminitis without cholestasis and no chronic liver sequelae, with subsequent normalization of her transaminases without treatment. Because her only symptom was decreased stool output and NBS results were unavailable, the CF diagnosis was delayed until she presented in extremis. Delayed meconium passage and decreased stool output during the first week of life should lead to suspicion and additional evaluation for CF while awaiting NBS results. Careful monitoring is indicated to prevent serious, life-threatening complications. The use of soy oil, medium chain triglycerides, olive oil, fish oil lipids for infants requiring prolonged parenteral nutrition may also be considered proactively to prevent cholestasis, particularly for high risk groups.


Assuntos
Fibrose Cística/diagnóstico , Íleo Meconial/diagnóstico , Colestase/prevenção & controle , Diagnóstico Tardio , Feminino , Óleos de Peixe/uso terapêutico , Humanos , Recém-Nascido , Lipídeos/administração & dosagem , Íleo Meconial/terapia , Azeite de Oliva/uso terapêutico , Nutrição Parenteral , Óleo de Soja/uso terapêutico , Triglicerídeos/administração & dosagem
11.
Curr Opin Pulm Med ; 26(6): 696-701, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32941351

RESUMO

PURPOSE OF REVIEW: The current review provides an overview of key psychological issues and challenges for the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator era of care. It discusses research from diagnosis and beyond, to patient-team communication with a particular focus on medical trials, adherence and living with CFTR modulators. RECENT FINDINGS: The impact of the diagnosis on parents is immense and the complexity of treatment now and in the future, are a challenge for both parents and teams. Communicating digitally is starting to become daily practice for many in CF care, with coronavirus disease 2019 accelerating this process. Participating in trials has a psychological impact, but most of all the (delayed) access and timing of accessing CFTR modulators is an important theme. Adherence remains of significance, both to 'old' and 'new' treatments. Living with CF in the era of CFTR modulators is beginning to impact on patients' quality of life, including new possibilities, opportunities and challenges. SUMMARY: Psychological care needs to engage and keep pace with the rapid medical changes. Some care priorities remain the same, including psychological screening and assessment, as well as psychoeducation, communication training and psychotherapy. The presence of CF psychologist in the CF clinic remains as important as ever.


Assuntos
Comunicação , Infecções por Coronavirus , Fibrose Cística/tratamento farmacológico , Fibrose Cística/psicologia , Adesão à Medicação , Pandemias , Pneumonia Viral , Betacoronavirus , Ensaios Clínicos como Assunto/psicologia , Fibrose Cística/diagnóstico , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Humanos , Qualidade de Vida
13.
S Afr Med J ; 110(7): 594-598, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32880327

RESUMO

Chronic rhinitis is a troublesome condition for sufferers. It is tempting to label all patients with chronic nasal symptoms as having allergic rhinitis (AR), but many such patients have other causes of chronic rhinitis that need a specific diagnosis and management strategy. Even when the patient fully fits the definition of AR, their condition will be best served by combining medication with ongoing patient education.


Assuntos
Doença Crônica , Rinite/diagnóstico , Doença Crônica/terapia , Transtornos da Motilidade Ciliar/diagnóstico , Fibrose Cística/diagnóstico , Diagnóstico Diferencial , Humanos , Educação de Pacientes como Assunto , Doenças da Imunodeficiência Primária/diagnóstico , Rinite/etiologia , Rinite/terapia , África do Sul
14.
Infect Dis Health ; 25(4): 239-241, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32763024

RESUMO

We report the first case of COVID-19 in a pregnant patient with cystic fibrosis. We describe the diagnosis, clinical course and management of the patient and their family with regards to clinical, social and infection control measures around delivery. This case highlights the importance of the cooperation of multidisciplinary teams to achieve good clinical outcomes in complex patients with COVID-19.


Assuntos
Infecções por Coronavirus/complicações , Fibrose Cística/virologia , Pneumonia Viral/complicações , Complicações Infecciosas na Gravidez/virologia , Adulto , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/transmissão , Fibrose Cística/diagnóstico , Parto Obstétrico , Feminino , Humanos , Transmissão Vertical de Doença Infecciosa , Masculino , Pandemias , Pneumonia Viral/transmissão , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/fisiopatologia , Resultado da Gravidez , Pessoas Transgênero
15.
J Vis Exp ; (161)2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32744517

RESUMO

Early detection and eradication of Pseudomonas aeruginosa within the lungs of cystic fibrosis patients can reduce the chance of developing chronic infection. The development of chronic P. aeruginosa infections is associated with a decline in lung function and increased morbidity. Therefore, there is a great interest in elucidating the reasons for the failure to eradicate P. aeruginosa with antibiotic therapy which occurs in approximately 10-40% of pediatric patients. One of many factors that can affect host clearance of P. aeruginosa and antibiotic susceptibility is variations in spatial organization (such as aggregation or biofilm formation) and polysaccharide production. Therefore, we were interested in visualizing the in situ characteristics of P. aeruginosa within the sputum of CF patients. A tissue clearing technique was applied to sputum samples after embedding the samples into a hydrogel matrix to retain the 3D structures relative to host cells. After tissue clearing, fluorescent labels and dyes were added to allow visualization. Fluorescence in situ hybridization was performed for the visualization of bacterial cells, binding of fluorescently labeled anti-Psl-antibodies for the visualization of the exopolysaccharide and DAPI staining to stain host cells to obtain structural insight. These methods allowed for the high-resolution imaging of P. aeruginosa within the sputum of CF patients via confocal laser scanning microscopy.


Assuntos
Fibrose Cística/diagnóstico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/patogenicidade , Escarro/microbiologia , Criança , Humanos , Masculino
16.
Zhonghua Er Ke Za Zhi ; 58(8): 646-652, 2020 Aug 02.
Artigo em Chinês | MEDLINE | ID: mdl-32842385

RESUMO

Objective: To analyze the clinical features of cystic fibrosis (CF) associated allergic bronchopulmonary aspergillosis (ABPA) in children. Methods: A retrospective study was performed in 22 children who were diagnosed with CF associated ABPA in Beijing Children's Hospital affiliated to Capital Medical University from March 2010 to March 2020. The clinical features, imaging characteristics, laboratory results and the prognosis were reviewed. Results: A total of 22 cases met the diagnostic criterion, including 12 males and 10 females. The age of diagnosis was (10.4±2.8) years and the age of onset was (5.5±4.4) years. Clinical manifestations included cough and expectoration (22 cases), recurrent wheezing (15 cases), hemoptysis (7 cases), failure to thrive (12 cases), pancreatitis (10 cases), hepatomegaly (7 cases), splenomegaly (4 cases) and steatorrhea (4 cases). CT scans of all the patients showed pulmonary infiltrates and central bronchiectasis, combined with mucoid impaction in 17 cases and high density mucus plug in 12 cases. Eosinophilia was found in 18 patients. Total IgE and serum levels of A. fumigatus-specific IgE were elevated in all 22 patients. Positive culture of sputum or bronchoalvedar lauage fluid for fungus were in 15 cases, with single Aspergillus infection in 8 cases and mixed Aspergillus infection in 3 cases. The predominant bacteria found in the airways were Pseudomonas aeruginosa (17 cases), followed by staphylococcas. aureus (6 cases) and stenotrophomonas. maltophilia (5 cases). Pulmonary function revealed obstructive ventilation dysfunction in 4 cases, mixed dysfunction in 11 cases, and small airway dysfunction in 4 cases. Regarding the treatment, 3 were treated only with systemic corticosteroid, while the remaining 19 cases also received antifungal agents.The follow up continued for 1-7 years, and 6 maintained remission, 10 had recurrent episodes, 1 died, and 5 lost to follow up. Conclusions: CF associated ABPA is extremely rare in China. The overlapping clinical, radiographic, and immunologic features of these two diseases make the diagnosis challenging. Systemic corticosteroids are considered the first-line therapy for these patients, and adjuvant antifungal agents may be helpful. Recurrence rate in our center is high.


Assuntos
Aspergilose Broncopulmonar Alérgica/complicações , Aspergillus fumigatus/isolamento & purificação , Fibrose Cística/complicações , Escarro/microbiologia , Aspergilose Broncopulmonar Alérgica/tratamento farmacológico , Criança , China , Fibrose Cística/diagnóstico , Fibrose Cística/microbiologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
18.
Am J Respir Crit Care Med ; 202(8): 1133-1145, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32569477

RESUMO

Rationale: In cystic fibrosis the major cause of morbidity and mortality is lung disease characterized by inflammation and infection. The influence of sphingolipid metabolism is poorly understood with a lack of studies using human airway model systems.Objectives: To investigate sphingolipid metabolism in cystic fibrosis and the effects of treatment with recombinant human acid ceramidase on inflammation and infection.Methods: Sphingolipids were measured using mass spectrometry in fully differentiated cultures of primary human airway epithelial cells and cocultures with Pseudomonas aeruginosa. In situ activity assays, Western blotting, and quantitative PCR were used to investigate function and expression of ceramidase and sphingomyelinase. Effects of treatment with recombinant human acid ceramidase on sphingolipid profile and inflammatory mediator production were assessed in cell cultures and murine models.Measurements and Main Results: Ceramide is increased in cystic fibrosis airway epithelium owing to differential function of enzymes regulating sphingolipid metabolism. Sphingosine, a metabolite of ceramide with antimicrobial properties, is not upregulated in response to P. aeruginosa by cystic fibrosis airway epithelia. Tumor necrosis factor receptor 1 is increased in cystic fibrosis epithelia and activates NF-κB signaling, generating inflammation. Treatment with recombinant human acid ceramidase, to decrease ceramide, reduced both inflammatory mediator production and susceptibility to infection.Conclusions: Sphingolipid metabolism is altered in airway epithelial cells cultured from people with cystic fibrosis. Treatment with recombinant acid ceramidase ameliorates the two pivotal features of cystic fibrosis lung disease, inflammation and infection, and thus represents a therapeutic approach worthy of further exploration.


Assuntos
Ceramidase Ácida/metabolismo , Ceramidase Ácida/farmacologia , Fibrose Cística/tratamento farmacológico , Pneumonia/diagnóstico , Infecções por Pseudomonas/diagnóstico , Esfingolipídeos/metabolismo , Adolescente , Células Epiteliais Alveolares/efeitos dos fármacos , Animais , Western Blotting/métodos , Células Cultivadas , Criança , Fibrose Cística/diagnóstico , Humanos , Inflamação/diagnóstico , Inflamação/tratamento farmacológico , Espectrometria de Massas/métodos , Camundongos , Pneumonia/tratamento farmacológico , Reação em Cadeia da Polimerase/métodos , Infecções por Pseudomonas/tratamento farmacológico , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Adulto Jovem
19.
Tunis Med ; 98(5): 420-422, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32548846

RESUMO

Cystic Fibrosis (CF) is a lethal autosomal recessive condition due to a defect at the level of the transmembrane conductance regulator gene which plays a role in cell homeostasis. Numerous mutations have been identified as the cause of this gene defect, with delF508 being one of the most common mutations in Tunisia. This is a case report describing, up to our knowledge, the second case of a patient with CF carrying a rare mutation: W19X. W19X is a nonsense mutation that has been previously identified in only one other Tunisian patient with CF. Since both incidence of this mutation have been described in Tunisia, it seems as if W19X is specific to Tunisian CF patient with significant morbidities. The information provided by this study contributes to defining the molecular spectrum of CF in Tunisia, in the aim of improving genetic testing and prenatal diagnosis.


Assuntos
Códon sem Sentido , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Fibrose Cística/diagnóstico , Fibrose Cística/patologia , Frequência do Gene , Testes Genéticos , Humanos , Triptofano/genética , Tunísia
20.
Artigo em Inglês | MEDLINE | ID: mdl-32375358

RESUMO

(1) Background: Diagnostic testing for cystic fibrosis (CF) is based on a sweat chloride test (SCT) considering the appropriate signs and symptoms of the disease and results of a gene mutation analysis. In 2014, the Istituto Superiore di Sanità (ISS) established a pilot Italian external quality assessment program for CF SCT (Italian EQA-SCT), which is now a third party service carried out by the ISS. (2) Methods: The ongoing scheme is prospective, enrollment is voluntary, and the payment of a fee is required. Results are shared through a dedicated web-facility. Assessment covers the analysis, interpretation, and reporting of results. (3) Results: Thirteen, fifteen, sixteen, and fifteen different laboratories, respectively, participated from 2015 to 2016 and from 2018 to 2019 in the Italian EQA-SCT scheme. Eleven different laboratories participated each year in all four rounds of the Italian EQA-SCT. (4) Conclusions: The overall results obtained from the laboratories participating constantly clearly show that their qualitative and quantitative performance improved significantly. This is due to the opportunity-after receiving the EQA results-to constantly review their performance and address any inconsistencies. We firmly believe that participation in the EQA program will improve the quality of participating laboratories and that EQA participation should become mandatory as a fundamental requirement for laboratory accreditation.


Assuntos
Fibrose Cística , Suor , Cloretos/análise , Fibrose Cística/diagnóstico , Humanos , Itália , Estudos Prospectivos , Garantia da Qualidade dos Cuidados de Saúde , Suor/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...