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1.
BMC Infect Dis ; 23(1): 845, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38036963

RESUMO

Respiratory syncytial virus (RSV) is the most common pathogen associated with acute lower respiratory tract infections in infants and young children worldwide. RSV commonly presents as bronchiolitis in young children; however, it can sometimes progress to pneumonia, respiratory failure, apnoea and even death. Although mucin1 (MUC1), a type of transmembrane glycoprotein present on airway epithelial surfaces, plays a crucial anti-inflammatory role in airway infections; however, its roles in RSV-associated acute lower respiratory tract infections have rarely been explored. In this study, we first revealed very high MUC1 protein levels in the exacerbation phase in sputum samples from children with RSV bronchiolitis. Because MUC1 is the downstream target of tumour necrosis factor-alpha (TNF-α) in RSV-infected A549 cells, we observed the inhibition of NF-κB activity, main downstream signalling of TNF-α and remarkably reduced levels of MUC1 in RSV-infected and TNF-α treated A549 cells. Furthermore, the cyclic adenosine monophosphate (cAMP) analogue (dbcAMP) downregulated the protein levels of p-IκBα and MUC1 in TNF-α-treated A549 cells. By contrast, a protein kinase A inhibitor (KT5720) up-regulated the levels of those proteins. dbcAMP and KT5720 had the same effects on MUC1 protein levels in RSV-infected A549 cells. In conclusion, we found that the cAMP-PKA-NF-κB pathway may play a role in the regulation of MUC-1 over-expression during RSV infection.


Assuntos
Bronquiolite , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Criança , Pré-Escolar , Humanos , Células A549 , Bucladesina/metabolismo , Células Epiteliais , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
2.
Transl Pediatr ; 11(10): 1624-1632, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36345444

RESUMO

Background: Salbutamol bronchodilator response (BDR) test and fractional exhaled nitric oxide (FeNO) have been recommended for the diagnosis of asthma in children, but FeNO levels is affected by many factors. Nonetheless, data of the effect on the FeNO values throughout the bronchodilator test and the differences in FeNO values between BDR positive (BDR+) and negative (BDR-) children with asthma are still limited. We aimed to evaluate the effect of the BDR test on FeNO and the differences in FeNO levels between BDR+ and BDR- children with asthma. Methods: This was a prospective, observational study performed over a 5-month period (December 2018 to April 2019) and involved 57 children with asthma. The FeNO levels at pre-spirometry, post-spirometry, and post-salbutamol BDR testing were estimated. Finally, the children were divided into two groups i.e., BDR+ and BDR-, and differences in the FeNO levels were compared between the two groups. Results: The spirometry results were normal in 2 patients (3.5%). There were 53 (93%) patients with obstructive lung disease, including 40 (70.2%), 11 (19.3%), and 2 (3.5%) patients with mild, moderate, and severe obstruction, respectively. The remaining two patients had mixed lesions (3.5%), none of which were restrictive. The baseline median FeNO levels were significantly higher in the BDR+ group than in the BDR- group [33.00 (23.78, 46.73) vs. 23.00 (9.80, 37.80), (P=0.048)]. Following spirometry, there was a statistically significant decrease in median FeNO levels from baseline to post-spirometry (P=0.002). However, there was no significant difference between the median FeNO levels at baseline and following the BDR test (P=0.976). The impact of spirometry on FeNO was not statistically different in BDR+ versus BDR- children (Z=-0.186, P=0.853); however, the impact of bronchodilators on FeNO exhibited a statistically significant difference between the two groups (Z=3.160, P=0.002). Conclusions: This study revealed dynamic changes in the FeNO levels during the BDR test. The use of a bronchodilator results in a statistically significant difference in FeNO levels between BDR+ and BDR- children with asthma. Moreover, spirometry leads to a marked decrease in the FeNO levels. Our results will allow clinicians to better interpret FeNO, BDR and pulmonary function outcomes and better develop clinical protocols.

3.
Microbiol Spectr ; 10(5): e0148822, 2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36169415

RESUMO

Pneumonia is the leading cause of death in children; the pathogens are often difficult to diagnose. In this study, the performance of metagenomic next-generation sequencing (mNGS) using bronchoalveolar lavage fluid (BALF) samples from 112 children with confirmed pneumonia has been evaluated. mNGS performed a significantly higher positive detection rate (91.07%, 95% confidence interval [CI] 83.80% to 95.40%) and coincidence rate against the final diagnosis (72.32%, 95% CI 62.93% to 80.15%) than that of conventional methods (70.54%, 95% CI 61.06% to 78.58% and 56.25%, 95% CI 46.57% to 65.50%, respectively) (P < 0.01 and P < 0.05, respectively). Bacteria, viruses, and their mixed infections were common in children with pneumonia. Streptococcus pneumoniae was the most common bacterial pathogen in children with pneumonia, while Haemophilus parainfluenzae and Haemophilus influenzae seemed more likely to cause nonsevere pneumonia in children. In contrast, human cytomegalovirus (CMV) infection and the simultaneous bacterial infections could cause severe pneumonia, especially in children with underlying diseases. After adjustments of antibiotics based on mNGS and conventional methods, the conditions improved in 109 (97.32%) children. mNGS of BALF samples has shown great advantages in diagnosing the pathogenic etiology of pneumonia in children, especially when considering the limited volumes of BALF and the previous use of empirical antibiotics, contributing to the timely adjustment of antibiotic treatments, which can potentially improve the prognosis and decrease the mortality. IMPORTANCE Our study indicates high efficiency of mNGS using BALF for the detection of causative pathogens that cause pneumonia in children. mNGS can be a potential diagnostic tool to supplement conventional methods for children's pneumonia.


Assuntos
Metagenômica , Pneumonia , Criança , Humanos , Líquido da Lavagem Broncoalveolar , Sensibilidade e Especificidade , Metagenômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Pneumonia/diagnóstico , Pneumonia/microbiologia , Bactérias/genética , Antibacterianos
4.
Front Genet ; 13: 875015, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464853

RESUMO

Interstitial lung disease (ILD) is a heterogeneous group of pulmonary disorders involving the lung interstitium and distal airways, also known as diffuse lung disease. The genetic defects resulting in alveolar surfactant protein dysfunction are a rare cause of ILD in pediatric patients. We report two unrelated pediatric patients with shortness of breath, dyspnea and hypoxemia, and the chest CT findings including patchy ground-glass opacity in both lung fields, suggestive of diffuse ILD. One patient was a full-term male infant who had shortness of breath a few hours after the birth, and then developed into severe respiratory distress syndrome (RDS). Whole exome sequencing revealed novel compound heterozygous variants in the ABCA3 gene (NM_001,089.3): paternally inherited c.4035+5G > A and c.668T > C (p.M223T), and maternally inherited c.1285+4A > C. The second patient was a 34-month-old boy with onset of chronic repeated cough and hypoxemia at 9 months of age. We unveiled novel compound heterozygous ABCA3 variants (c.704T > C, p.F235S; c.4037_4040del, p.T1346Nfs*15) in this patient. Surfactant protein dysfunction due to bi-allelic mutations in the ABCA3 gene was the cause of ILD in two patients. The novel mutations found in this study expanded the spectrum of known mutations in the ABCA3 gene.

5.
J Exp Med ; 219(3)2022 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-35044462

RESUMO

Group 2 innate lymphoid cells (ILC2s) have emerged as critical mediators in driving allergic airway inflammation. Here, we identified angiotensin (Ang) II as a positive regulator of ILC2s. ILC2s expressed higher levels of the Ang II receptor AT1a, and colocalized with lung epithelial cells expressing angiotensinogen. Administration of Ang II significantly enhanced ILC2 responses both in vivo and in vitro, which were almost completely abrogated in AT1a-deficient mice. Deletion of AT1a or pharmacological inhibition of the Ang II-AT1 axis resulted in a remarkable remission of airway inflammation. The regulation of ILC2s by Ang II was cell intrinsic and dependent on interleukin (IL)-33, and was associated with marked changes in transcriptional profiling and up-regulation of ERK1/2 phosphorylation. Furthermore, higher levels of plasma Ang II correlated positively with the abundance of circulating ILC2s as well as disease severity in asthmatic patients. These observations reveal a critical role for Ang II in regulating ILC2 responses and airway inflammation.


Assuntos
Angiotensina II/metabolismo , Imunidade Inata , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Doenças Respiratórias/etiologia , Doenças Respiratórias/metabolismo , Animais , Biomarcadores , Hiper-Reatividade Brônquica/etiologia , Hiper-Reatividade Brônquica/metabolismo , Hiper-Reatividade Brônquica/patologia , Modelos Animais de Doenças , Suscetibilidade a Doenças , Inflamação , Interleucina-33/metabolismo , Camundongos , Camundongos Knockout , Receptor Tipo 1 de Angiotensina/genética , Doenças Respiratórias/patologia
6.
BMC Pediatr ; 21(1): 297, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34210262

RESUMO

BACKGROUND: Infantile malignant osteopetrosis (IMO) is a rare autosomal recessive disease characterized by a higher bone density in bone marrow caused by the dysfunction of bone resorption. Clinically, IMO can be diagnosed with medical examination, bone mineral density test and whole genome sequencing. CASE PRESENTATION: We present the case of a 4-month-old male infant with abnormal skull development, hypocalcemia and premature closure of the cranial sutures. Due to the hyper bone density showed by his radiographic examination, which are characteristic patterns of IMO, we speculated that he might be an IMO patient. In order to confirm this diagnosis, a high-precision whole exome sequencing of the infant and his parents was performed. The analysis of high-precision whole exome sequencing results lead to the identification of two novel heterozygous mutations c.504-1G > C (a splicing site mutation) and c.1371delC (p.G458Afs*70, a frameshift mutation) in gene TCIRG1 derived from his parents. Therefore, we propose that there is a close association between these two mutations and the onset of IMO. CONCLUSIONS: To date, these two novel mutations in gene TCIRG1 have not been reported in the reference gene database of Chinese population. These variants have likewise not been reported outside of China in the Genome Aggregation Database (gnomAD). Our case suggests that the use of whole exome sequencing to detect these two mutations will improve the identification and early diagnosis of IMO, and more specifically, the identification of homozygous individuals with TCIRG1 gene mutation. We propose that these mutations in gene TCIRG1 could be a novel therapeutic target for the IMO in the future.


Assuntos
Osteopetrose , ATPases Vacuolares Próton-Translocadoras , China , Homozigoto , Humanos , Lactente , Masculino , Mutação , Osteopetrose/diagnóstico por imagem , Osteopetrose/genética , ATPases Vacuolares Próton-Translocadoras/genética , ATPases Vacuolares Próton-Translocadoras/metabolismo
7.
Braz J Med Biol Res ; 54(4): e9850, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33656056

RESUMO

Respiratory syncytial virus (RSV) infection is the main cause of lower respiratory tract infection in children. However, there is no effective treatment for RSV infection. Here, we aimed to identify potential biomarkers to aid in the treatment of RSV infection. Children in the acute and convalescence phases of RSV infection were recruited and proteomic analysis was performed to identify differentially expressed proteins (DEPs). Subsequently, promising candidate proteins were determined by functional enrichment and protein-protein interaction network analysis, and underwent further validation by western blot both in clinical and mouse model samples. Among the 79 DEPs identified in RSV patient samples, 4 proteins (BPGM, TPI1, PRDX2, and CFL1) were confirmed to be significantly upregulated during RSV infection. Functional analysis showed that BPGM and TPI1 were mainly involved in glycolysis, indicating an association between RSV infection and the glycolysis metabolic pathway. Our findings provide insights into the proteomic profile during RSV infection and indicated that BPGM, TPI1, PRDX2, and CFL1 may be potential therapeutic biomarkers or targets for the treatment of RSV infection.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Biomarcadores , Criança , Humanos , Proteômica
8.
Ecotoxicol Environ Saf ; 210: 111864, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33412282

RESUMO

Volatile organic compounds (VOCs) are important and ubiquitous air pollutants, which may lead to a significant increase in the prevalence of respiratory diseases. To investigate the relationships between VOCs exposure and childhood asthma, 252 asthmatic children and 69 healthy children were recruited. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG, a biomarker of oxidative DNA damage), trans-3'-hydroxycotinine (OH-Cot, a biomarker of passive smoking) and 27 VOC metabolites were simultaneously determined by an ultra-high-performance liquid chromatography-tandem mass spectrometer. Results showed that levels of 8-OHdG and most VOC metabolites in asthmatic children were significantly higher than those in healthy children. More than half of the VOC metabolites were significantly and positively associated with OH-Cot with maximal ß coefficient of 0.169, suggesting that second-hand smoking is one important source of VOCs exposure for children in Guangzhou. Significant dose-response relationships between most VOC metabolites and 8-OHdG were observed. Each unit increase in ln-transformed VOC metabolite levels was significantly associated with 5.5-32% increase in ln-transformed 8-OHdG level. Moreover, each unit increase in ln-transformed 8-OHdG level was associated with an 896% increased odd ratios (OR) of asthma in children (OR = 9.96, 95% confidence intervals (CI): 4.75, 20.9), indicating that oxidative stress induced by VOCs exposure may have a significant impact on childhood asthma. Urinary 3-&4-Methylhippuric acid (3-&4-MHA, OR: 5.78, 95% CI: 3.50, 9.54), rac 2-Aminothiazoline-4-carboxylic acid (ATCA, OR: 2.90, 95% CI: 1.69, 4.99) and N-Acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHBMA, OR: 2.76, 95% CI: 1.73, 4.43) which may derive from m/p-xylene, cyanide and 1,3-butadiene exposure, respectively, could significantly and maximally increase the odds of asthma. Interestingly, they also had the strongest associations with 8-OHdG among all investigated VOC metabolites. Moreover, DHBMA strongly correlated with most VOC metabolites. Hence, DHBMA is a suitable biomarker to indicate not only VOCs exposure profile, but also the DNA damage-mediated asthma induced by VOCs.


Assuntos
Asma/urina , Poluentes Ambientais/urina , Estresse Oxidativo , Poluição por Fumaça de Tabaco/efeitos adversos , Compostos Orgânicos Voláteis/urina , 8-Hidroxi-2'-Desoxiguanosina/urina , Asma/epidemiologia , Monitoramento Biológico , Biomarcadores/urina , Criança , China/epidemiologia , Cotinina/análogos & derivados , Cotinina/urina , Poluentes Ambientais/metabolismo , Feminino , Humanos , Masculino , Compostos Orgânicos Voláteis/metabolismo
9.
Braz. j. med. biol. res ; 54(4): e9850, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1153545

RESUMO

Respiratory syncytial virus (RSV) infection is the main cause of lower respiratory tract infection in children. However, there is no effective treatment for RSV infection. Here, we aimed to identify potential biomarkers to aid in the treatment of RSV infection. Children in the acute and convalescence phases of RSV infection were recruited and proteomic analysis was performed to identify differentially expressed proteins (DEPs). Subsequently, promising candidate proteins were determined by functional enrichment and protein-protein interaction network analysis, and underwent further validation by western blot both in clinical and mouse model samples. Among the 79 DEPs identified in RSV patient samples, 4 proteins (BPGM, TPI1, PRDX2, and CFL1) were confirmed to be significantly upregulated during RSV infection. Functional analysis showed that BPGM and TPI1 were mainly involved in glycolysis, indicating an association between RSV infection and the glycolysis metabolic pathway. Our findings provide insights into the proteomic profile during RSV infection and indicated that BPGM, TPI1, PRDX2, and CFL1 may be potential therapeutic biomarkers or targets for the treatment of RSV infection.


Assuntos
Humanos , Criança , Vírus Sincicial Respiratório Humano , Infecções por Vírus Respiratório Sincicial , Biomarcadores , Proteômica
10.
Environ Pollut ; 266(Pt 2): 115220, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32707352

RESUMO

As previous studies found that the direct associations between urinary polycyclic aromatic hydrocarbon (PAH), benzene and toluene (BT) metabolites and the decreased lung function were not conclusive, we further investigated relationship of oxidative damage and airway inflammation induced by PAHs and BTs exposure with lung function. A total of 262 children diagnosed with asthma and 72 heathy children were recruited. Results showed that asthmatic children had higher levels of PAHs and BTs exposure, as well as Malonaldehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) compared with healthy children. Furthermore, binary logistic regression showed that each unit increases in level of urinary 2-&3-hydroxyfluorene (2-&3-OHF), 2-hydroxyphenanthrene (2-OHPhe), 1-hydroxyphenanthrene (1-OHP) and S-phenylmercapturic acid (S-PMA) were significantly associated with an elevated risk of asthma in children with odds ratios of 1.5, 2.3, 1.7 and 1.4, respectively, suggesting that PAHs and BTs exposure could increase the risk of asthma for children. Neither PAH nor BT metabolite could comprehensively indicate the decreased lung function as only 2-&3-OHF and 1-OHP were significantly and negatively correlated with forced vital capacity (FVC). Moreover, levels of most individual PAH and BT metabolite were significantly correlated to MDA and 8-OHdG. Further hierarchical regression analysis indicated that MDA and 8-OHdG levels did not show significant effects on the decreased lung function, suggesting that they are not the suitable biomarkers to indirectly indicate the altered lung function induced by PAHs and BTs. Urinary 2-OHPhe and 1-&9-hydroxyphenanthrene (1-&9-OHPhe) were significantly correlated with fractional exhaled nitric oxide (FeNO). Moreover, FeNO significantly contributed to decreased lung function and explained 7.7% of variance in ratio of forced expiratory volume in 1 s (FEV1) and FVC (FEV1/FVC%). Hence, FeNO, rather than oxidative damage indicators or any urinary PAH and BT metabolite, is more sensitive to indirectly reflect the decreased lung function induced by PAHs and BTs exposure for asthmatic children.


Assuntos
Asma , Hidrocarbonetos Policíclicos Aromáticos , Benzeno , Biomarcadores , Criança , Humanos , Inflamação , Estresse Oxidativo , Tolueno
11.
Medicine (Baltimore) ; 99(4): e18584, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977849

RESUMO

To evaluate epidemiology and risk factors of severe adenovirus respiratory infection in hospitalized children in Guangzhou, China.A retrospective review study was conducted, and 542 children hospitalized for adenovirus respiratory infection, were included from January 2011 to December 2014. Patients were younger than 14 years. Disease severity was classified into severe and mild. Laboratory tests and clinical characteristics were analyzed for risk factors of adenovirus respiratory infection by multivariable logistic regression.Among these 542 children, 92.1% were aged < 6 years. Clinical diagnoses were upper respiratory infections in 11.6%, bronchiolitis in 16%, and mild pneumonia in 62.0% of children. Severe pneumonia rate was 10.3% (56/542) with a mortality rate of 0.9% (5/542). The cohort comprised 542 patients; 486 patients with mild adenovirus respiratory infection and 56 patients with severe adenovirus respiratory infection. Multivariable logistic regression was used to confirm associations between variables and adenovirus respiratory infection, after age and gender adjustment. Hospital stay, still significantly associated with adenovirus respiratory infection. Patients with longer hospital stay (odds ratio [OR] = 1.20, 95% confidence interval [CI]: 1.13-1.28, P < .001), lower LYMPH (OR = 0.73 95% CI: 0.55-0.99, P = .039), and increased LDH (OR = 1.002, 95% CI: 1.001-1.003, P =  .001) had a higher risk of severe adenovirus respiratory infection.Adenovirus is a major pathogen in hospitalized children with respiratory infection. High serum LDH level and low lymphocyte count could be used as predictors of adenovirus respiratory infection severity in children.


Assuntos
Infecções por Adenovirus Humanos/epidemiologia , Criança Hospitalizada/estatística & dados numéricos , Infecções Respiratórias/epidemiologia , Infecções por Adenovirus Humanos/mortalidade , Adolescente , Fatores Etários , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Tempo de Internação , Modelos Logísticos , Masculino , Pneumonia/epidemiologia , Infecções Respiratórias/mortalidade , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais
12.
Anal Bioanal Chem ; 411(29): 7841-7855, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31748896

RESUMO

Human beings are inevitably exposed to volatile organic compounds (VOCs) of anthropogenic emissions as they are ubiquitous atmospheric pollutants. Smoking is an important exposure route of VOCs for the general population. Health effects induced by VOC exposure raise more concerns as they are identified with carcinogenicity, genotoxicity, neurotoxicity, and reproductive toxicity. trans-3'-Hydroxycotinine (OH-Cot) is a urinary biomarker of smoking, and 8-hydroxy-2'-deoxyguanosine (8-OHDG) is a urinary biomarker of DNA oxidative damage. To develop a method for quantifying VOC exposure levels of the general population and assessing the health risks induced by VOCs from second-hand smoking, an effective, rapid, and high-throughput method for the simultaneous determination of 31 metabolites of VOCs, 8-OHDG, and OH-Cot using solid-phase extraction coupled with UPLC-MS/MS was developed and validated. Method precision and accuracy, extraction recoveries, matrix effects, and storage stabilities of most analytes met the criterion (80-120%). Extraction recoveries increased from 85.1 to 100% after adjustment by isotoped internal standards (ISs). Furthermore, 13C- and 15N-labeled ISs were more effective to reduce the influence of matrix effects on recoveries and precisions than the deuterated analogs (73.0-116% vs. 53.6-140%). This developed method was successfully applied to determine urine samples collected from children. Results showed that N-acetyl-S-(3,4-dihydrobutyl)-L-cysteine, 2,2'-thiodiacetic acid (TGA), and N-acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine (HPMMA) were well correlated with 8-OHDG with coefficients higher than 0.82, indicating those VOCs might easily lead to DNA damage. In conclusion, our co-monitoring of metabolites of VOCs with 8-OHDG and OH-Cot in one method provides a robust analytical method, which not only suggests the potential adverse health effects induced by VOCs but also discriminates and evaluates the contribution of passive smoking in human VOC exposure. Graphical abstract.


Assuntos
8-Hidroxi-2'-Desoxiguanosina/urina , Cromatografia Líquida/métodos , Cotinina/análogos & derivados , Espectrometria de Massas em Tandem/métodos , Compostos Orgânicos Voláteis/urina , 8-Hidroxi-2'-Desoxiguanosina/normas , Estudos de Casos e Controles , Cotinina/normas , Cotinina/urina , Humanos , Isótopos de Nitrogênio , Padrões de Referência , Fumar/urina , Compostos Orgânicos Voláteis/normas
14.
Bioengineered ; 8(4): 374-382, 2017 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-27786573

RESUMO

Lobar pneumonia, one of the community-acquired pneumonia (CAP), is a common pediatric low respiratory tract infection. Calpains are Ca2+-activated cysteine proteases whose activation mechanism is elusive. The present study was undertaken to detect the role and mechanism of calpains in pediatric lobar pneumonia. The human acute lung infection model (ALIM) was constructed and infected by Streptococcus. Enzyme-linked immunosorbent assay (ELISA) was used to measure interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-α. We observed the lactate dehydrogenase (LDH) release, calpains activity and calpain inhibitor effects in ALIM. The expression of proliferating cell nuclear antigen (PCNA) protein was quantified by western blotting. Then the effects of calpain 1 and 2 knockdown on expressions of inflammation factors and PCNA protein, LDH release and apoptosis were evaluated in lung MRC-5 cells. In constructed ALIM, expressions of IL-6 (P < 0.01), IL-8 (P < 0.01), TNF-α (P < 0.05) and PCNA protein (P < 0.05) were significantly reduced by the calpain inhibitor. Expressions of IL-6, IL-8, TNF-α, PCNA protein and relative LDH release were statistically reduced by the small interfering (si) RNA-calpain 1 and 2 in MRC-5 cells (P < 0.05). Calpains silence increased apoptotic cells from 5% (negative control) to more than 20% in MRC-5 cells. The present study suggests that calpains possess a significant effect on inflammations, cell proliferation and apoptosis. Suppression of calpains may provide a potential therapeutic target of lobar pneumonia.


Assuntos
Calpaína/imunologia , Citocinas/imunologia , Fatores Imunológicos/imunologia , Pulmão/imunologia , Pneumonia/imunologia , Apoptose/imunologia , Proliferação de Células , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Modelos Biológicos
15.
Springerplus ; 5(1): 1622, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27722041

RESUMO

Bronchiolitis obliterans (BO) is an uncommon and severe sequela of chronic obstructive lung disease in children that results from an insult to the lower respiratory tract. Few prognostic factors achieved worldwide acknowledgment. In the present study, we retrospectively collected the children with respiratory adenoviral infection and identified the predictive factors of BO. In the period between Jan 2011 and December 2014, the consecutive in-hospital acute respiratory infection children with positive result for adenovirus were enrolled into the present study. High resolution computerized tomography and clinical symptoms were utilized as the diagnostic technique for BO. Multivariate analysis using a Logistic proportional hazards model was used to test for independent predictors of BO. A total of 544 children were included with 14 (2.57 %) patients developed BO. Compared with children without BO, BO children presented higher LDH (523.5 vs. 348 IU/ml, p = 0.033), lower blood lymphocyte count (2.23 × 109/L vs. 3.24 × 109/L, p = 0.025) and higher incidence of hypoxemia (78.6 vs. 20.8 %, p = 0.000). They presented relatively persistent fever (15.5 vs. 7 days, p = 0.000) and needed longer treatment in hospital (19.5 vs. 7 days, p = 0.000). Concerning treatment, they were given more intravenous γ-globulin (85.7 vs. 36.8 %, p = 0.000), glucocorticoids (78.6 vs. 24.3 %, p = 0.000) and mechanical ventilation (35.7 vs. 5.5 %, p = 0.001). Multiple analyses determined that hypoxemia was the only independent predictor for BO. The present study identified hypoxemia as the independent predictive factor of BO in adenoviral infected children, which was a novel and sensitive predictor for BO.

16.
Indian J Pediatr ; 83(8): 787-91, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26821544

RESUMO

OBJECTIVE: To analyze the clinical and imagenological characteristics of acute Exogenous lipoid pneumonia (ELP), explore its risk factors, and assess the potential role of multiple bronchoalveolar lavages (BALs) and steroid therapy in the treatment of children with acute ELP. METHODS: Between May 2011 and July 2014, 33 pediatric patients with pneumonia caused by aspiration of oil-based substances were admitted to the Guangzhou Women and Children's Medical Center, Guangdong, China. Data on the demographics of these patients, as well as that on clinical presentations, imagenological characteristics, history of ingestion, laboratory observations, treatment protocol, response to therapy, BAL findings, and treatment outcomes were collected. RESULTS: The study group consisted of 23 boys (69.7 %) and 10 girls (30.3 %), with ages ranging from 4 mo to 4 y. They were admitted to the hospital 2 h to 13 d after ingesting the oil-based substance. By the time of admission, most patients presented with respiratory distress and other symptoms, including tachypnea (n = 21), cough (n = 25), mild fever (n = 18), progressive dyspnea (n = 12), and pneumorrhagia (n = 5); six patients received mechanical ventilation because of complicated respiratory distress syndrome. The most common laboratory observations were leukocytosis (25 of 33, 75.8 %), neutrophilia (23 of 33, 69.7 %), and anemia (8 of 33, 24.2 %). Serum biochemical examination showed elevated sedimentation rates (24 of 33, 72.7 %), lactate dehydrogenase levels (18 of 33, 54.5 %), and C-reactive protein levels (17 of 33, 51.5 %). The most common finding on computed tomography (CT) scans was areas of consolidation. Within the follow-up duration of 2 wk to 6 mo, all patients with clinical symptoms of ELP experienced remission, and none died. The CT scans of most of the cases were normal by 1 to 3 mo, except for two patients who showed complete improvement 6 mo after treatment. CONCLUSIONS: It was found that multiple BALs combined with steroid therapy result in significant improvement of clinical, radiologic, and laboratory parameters in children with acute ELP. Further, some traditional practices may predispose children to ELP, even in the absence of underlying risk factors. Finally, pneumorrhagia and acute respiratory distress syndrome may be the main complications of acute ELP in children.


Assuntos
Pneumonia Lipoide , Lavagem Broncoalveolar , Pré-Escolar , China , Tosse , Feminino , Humanos , Lactente , Masculino , Pneumonia Lipoide/patologia , Pneumonia Lipoide/fisiopatologia , Tomografia Computadorizada por Raios X
17.
Open Med (Wars) ; 10(1): 479-482, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-28352740

RESUMO

To observe a therapeutic effect of macrolide antibiotics in children with Pseudomonas aeruginosa pneumonia. Fifty-four cases of children with Pseudomonas aeruginosa pneumonia were randomly divided into an observation group (n=30) and a control group (n=24). The observation group was treated with macrolide antibiotics and cefoperazone/sulbactam. The control group was treated with cefoperazone/sulbactam during a course of 10-14 days. The total effective rate was 93.3% in the observation group, and 58.3% in the control group, and results in the observation group were superior to the control group notably (P>0.05). There were no significant differences in bacterial clearance rate, adverse reaction rate between two groups (P>0.05). The combined application of cefoperazone/sulbactam with macrolide antibiotics to treat Pseudomonas aeruginosa pneumonia in children would be a more effective clinical method.

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