SERPINB3 (Serpin Peptidase Inhibitor, Clade B (Ovalbumin), Member 3)

Review on SERPINB3 (Serpin Peptidase Inhibitor, Clade B (Ovalbumin), Member 3), with data on DNA, on the protein encoded, and where the gene is implicated

Transitioning adolescents living with HIV/AIDS to adult-oriented health care: an emerging challenge

OBJECTIVE: To review the literature on transition from pediatric to adult-oriented health care and discuss this issue in the specific context of chronic conditions. SOURCES: MEDLINE and LILACS were searched for relevant English and French-language articles published between 1990 and 2010. SUMMARY OF THE FINDINGS: The transition of adolescents with chronic diseases from pediatric care to adult-oriented services has been a growing concern among pediatric specialties. In recent years, young people living with HIV/AIDS have begun to reach adulthood, giving rise to several challenges. The studies reviewed herein discuss such relevant topics as: the difference between transfer, an isolated event, and transition, a gradual process; the transition models used in different services; the importance of transitioning in a planned and individualized manner; the need for comprehensive interaction between pediatric and adult-oriented care teams; the importance of joint participation of adolescents, their families, and health professionals in the process; barriers to and factors that promote successful transitions; and the special needs of adolescents with HIV/AIDS in this important period of life. CONCLUSIONS: Several authors agree that transitioning adolescents to adult-oriented health care should be a gradual process not determined by age alone. It requires a plan established with ample dialogue among adolescents, their families, and pediatric and adult care teams. However, there is little evidence to support any specific model of health care transition. This should prompt researchers to conduct more prospective studies on the theme, especially in more vulnerable groups such as adolescents living with HIV/AIDS.OBJETIVO: Revisar a literatura sobre transição de adolescentes da pediatria para a clínica de adultos, com enfoque na clínica da AIDS, discutindo o tema no contexto das doenças crônicas. FONTES DOS DADOS: A pesquisa bibliográfica utilizou os bancos de dados MEDLINE e LILACS (1990-2010), selecionando artigos disponíveis em inglês ou francês. SÍNTESE DOS DADOS: A transição de adolescentes com doenças crônicas, sempre atendidos por pediatras, para os serviços de adultos, tem sido uma crescente preocupação nas diversas especialidades pediátricas. Mais recentemente, jovens vivendo com HIV/AIDS estão atingindo essa fase e apresentando diversas dificuldades. Os estudos avaliados nessa revisão discutem alguns tópicos relevantes, como: a diferença entre transferência, um evento isolado, e transição, um processo gradual; os modelos utilizados nos diversos serviços; a importância de a transição ser feita de maneira planejada e individualizada; a necessidade de ampla interação entre as equipes pediátricas e os serviços de adultos; a importância da participação conjunta dos adolescentes, familiares e profissionais de saúde; as barreiras e os fatores que favorecem uma transição bem-sucedida; as necessidades e particularidades dos adolescentes com HIV/AIDS nesse momento importante de mudanças. CONCLUSÕES: Vários autores concordam que a transição de adolescentes para os serviços de adultos deva ser um processo gradual, não determinado apenas pela idade. É preciso um planejamento que envolva adolescentes, familiares e equipe dos serviços pediátricos e de adultos. No entanto, há pouca evidência que privilegie um modelo específico de transição, o que lança o desafio para a realização de mais estudos prospectivos sobre o tema, especialmente em grupos de maior vulnerabilidade, como o de adolescentes vivendo com HIV/AIDS.46547

Hypoxia up-regulates SERPINB3 through HIF-2\u3b1 in human liver cancer cells.

SERPINB3 is a cysteine-proteases inhibitor up-regulated in a significant number of cirrhotic patients carrying hepatocellular carcinoma (HCC) and recently proposed as a prognostic marker for HCC early recurrence. SERPINB3 has been reported to stimulate proliferation, inhibit apoptosis and, similar to what reported for hypoxia, to trigger epithelial-to-mesenchymal transition (EMT) and increased invasiveness in liver cancer cells. This study has investigated whether SERPINB3 expression is regulated by hypoxia-related mechanisms in liver cancer cells. Exposure of HepG2 and Huh7 cells to hypoxia up-regulated SERPINB3 transcription, protein synthesis and release in the extracellular medium. Hypoxia-dependent SERPINB3 up-regulation was selective (no change detected for SERPINB4) and operated through hypoxia inducible factor (HIF)-2\u3b1 (not HIF-1\u3b1) binding to SERPINB3 promoter, as confirmed by chromatin immuno-precipitation assay and silencing experiments employing specific siRNAs. HIF-2\u3b1-mediated SERPINB3 up-regulation under hypoxic conditions required intracellular generation of ROS. Immuno-histochemistry (IHC) and transcript analysis, performed in human HCC specimens, revealed co-localization of the two proteins in liver cancer cells and the existence of a positive correlation between HIF-2\u3b1 and SERPINB3 transcript levels, respectively. Hypoxia, through HIF-2\u3b1-dependent and redox-sensitive mechanisms, up-regulates the transcription, synthesis and release of SERPINB3, a molecule with a high oncogenic potential

[Pathology of chronic obstructive pulmonary disease]

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder of the lung characterized by poorly reversible airflow limitation. It is not a unique disease entity but rather a complex of conditions which include emphysema, chronic bronchitis and, sometimes, asthma. Moreover, COPD is a progressive disease often associated with exacerbations. Cigarette smoking, which is the most important risk factor for the development of COPD, induces pathological changes involving lung parenchyma, peripheral airways and central airways. Since lung parenchyma and peripheral airways are the sites responsible for airflow limitation and central airways are the main site of mucus hypersecretion, pathological changes in these compartments may be relevant in the development of COPD

Nintedanib Treatment for Idiopathic Pulmonary Fibrosis Patients Who Have Been Switched from Pirfenidone Therapy: A Retrospective Case Series Study

BACKGROUND: The efficacy and effectiveness of nintedanib as a first-line therapy in idiopathic pulmonary fibrosis (IPF) patients have been demonstrated by clinical trials and real-life studies. Our aim was to examine the safety profile and effectiveness of nintedanib when it is utilized as a second-line treatment in subjects who have discontinued pirfenidone. METHODS: The medical charts of 12 patients who were switched from pirfenidone to nintedanib were examined retrospectively. The drug's safety was defined by the number of adverse events (AEs) that were reported; disease progression was evaluated based on the patient's vital status and changes in forced vital capacity (FVC) at 12-month follow-up. RESULTS: The numbers of patients experiencing AEs and of the AEs per patient in our study group didn't significantly differ with respect to a group of 56 individuals who were taking nintedanib as a first-line therapy during the study period (5/12 vs. 22/56; p = 0.9999, and 0.00 (0.00-1.00) vs. 0.00 (0.00-3.00); p = 0.517, respectively). Two out of the 3 patients who had been switched to nintedanib due to a rapid disease progression showed stabilized FVC values. CONCLUSIONS: Nintedanib was found to have an acceptable safety profile in the majority of the IPF patients switched from pirfenidone. Prospective studies are warranted to determine if the drug can effectively delay disease progression in these patients

α1-Antitrypsin Polymerizes in Alveolar Macrophages of Smokers With and Without α1-Antitrypsin Deficiency

BACKGROUND: The deficiency of α1-antitrypsin (AAT) is secondary to misfolding and polymerization of the abnormal Z-AAT in liver cells and is associated with lung emphysema. Alveolar macrophages (AM) produce AAT, however it is not known if Z-AAT can polymerize in AM, further decreasing lung AAT and promoting lung inflammation. AIMS: To investigate if AAT polymerizes in human AM and to study the possible relation between polymerization and degree of lung inflammation. METHODS: Immunohistochemical analysis with 2C1 monoclonal antibody specific for polymerized AAT was performed in sections of: 9 lungs from individuals with AAT deficiency (AATD) and severe COPD, 35 smokers with normal AAT levels of which 24 with severe COPD and 11 without COPD, and 13 non-smokers. AM positive for AAT polymers were counted and expressed as percentage of total AM in lung. RESULTS: AAT polymerization was detected in [27(4-67)%] of AM from individuals with AATD but also in AM from smokers with normal AAT with [24(0-70)%] and without [24(0-60)%] COPD, but not in AM from non-smokers [0(0-1.5)%] (p<0.0001). The percentage of AM with polymerized AAT correlated with pack-years smoked (r=0.53,p=0.0001), FEV1/FVC (r=-0.41,p=0.005), Small Airways Disease (r=0.44,p=0.004), number of CD8+T-cells and neutrophils in alveolar walls (r=0.51,p=0.002; r=0.31,p=0.05 respectively). CONCLUSIONS: Polymerization of AAT in alveolar macrophages occurs in lungs of individuals with AATD but also in smokers with normal AAT levels with or without COPD. Our findings highlight the similarities in the pathophysiology of COPD in individuals with and without AATD, adding a potentially important step to the mechanism of COPD

Exhaled breath condensate pH as a biomarker of COPD severity in ex-smokers

Endogenous airway acidification, as assessed by exhaled breath condensate (EBC) pH, is present in patients with stable COPD. The aim of this study was to measure EBC pH levels in a large cohort of COPD patients and to evaluate associations with functional parameters according to their smoking status