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1.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(9): 877-881, 2021.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34535200

RESUMO

OBJECTIVES: To study the efficacy of Huaiqihuang granules as adjuvant therapy for bronchial asthma in children. METHODS: A multicenter, prospective, and registered real-world study was performed for the children, aged 2-5 years, who had a confirmed diagnosis of bronchial asthma in the outpatient service of 21 hospitals in China. Among these children, the children treated with medications for long-term asthma control (inhaled corticosteroid and/or leukotriene receptor antagonist) without Huaiqihuang granules were enrolled as the control treatment group, and those treated with medications for long-term asthma control combined with Huaiqihuang granules were enrolled as the combined treatment group. The medical data of all children were collected. Outpatient or telephone follow-up was performed at weeks 4, 8, 12, 20, 28, and 36 after treatment, including asthma attacks and rhinitis symptoms. A statistical analysis was performed for the changes in these indices. RESULTS: There was no significant difference in the frequency of asthma attacks or rhinitis attacks between the two groups before treatment (P>0.05). After treatment, the combined treatment group had significantly lower frequencies of asthma attacks, severe asthma attacks, and rhinitis attacks compared with the control treatment group (P<0.05). There was no signification difference in the incidence rate of adverse reactions between the two groups (P=0.667). CONCLUSIONS: Huaiqihuang granules in addition to medications for long-term asthma control can alleviate the symptoms of bronchial asthma and rhinitis and improve the level of asthma control in children with bronchial asthma, with good safety and little adverse effect. Citation.


Assuntos
Asma , Medicamentos de Ervas Chinesas , Asma/tratamento farmacológico , Criança , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Estudos Prospectivos , Qualidade de Vida
2.
Front Cell Infect Microbiol ; 11: 695134, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368015

RESUMO

The objective of this study was to evaluate the value of molecular methods in the management of community-acquired pneumonia (CAP) in children. Previously developed mass spectrometry (MS)-based methods combined with quantitative real-time PCR (combined-MS methods) were used to describe the aetiology and evaluate antibiotic therapy in the enrolled children. Sputum collected from 302 children hospitalized with CAP were analyzed using the combined-MS methods, which can detect 19 viruses and 12 bacteria related to CAP. Based on the results, appropriate antibiotics were determined using national guidelines and compared with the initial empirical therapies. Respiratory pathogens were identified in 84.4% of the patients (255/302). Co-infection was the predominant infection pattern (51.7%, 156/302) and was primarily a bacterial-viral mixed infection (36.8%, 111/302). Compared with that using culture-based methods, the identification rate for bacteria using the combined-MS methods (61.8%, 126/204) increased by 28.5% (p <0.001). Based on the results of the combined-MS methods, the initial antibiotic treatment of 235 patients was not optimal, which mostly required switching to ß-lactam/ß-lactamase inhibitor combinations or reducing unnecessary macrolide treatments. Moreover, using the combined-MS methods to guide antibiotic therapy showed potential to decrease the length of stay in children with severe CAP. For children with CAP, quantitative molecular testing on sputum can serve as an important complement to traditional culture methods. Early aetiology elucidated using molecular testing can help guide the antibiotic therapy.


Assuntos
Infecções Comunitárias Adquiridas , Pneumonia , Antibacterianos/uso terapêutico , Bactérias/genética , Criança , Infecções Comunitárias Adquiridas/tratamento farmacológico , Humanos , Espectrometria de Massas , Pneumonia/tratamento farmacológico
3.
Virol Sin ; 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34398429

RESUMO

Human respiratory syncytial virus (RSV) is a major pathogen of acute lower respiratory tract infection among young children. To investigate the prevalence and genetic characteristics of RSV in China, we performed a molecular epidemiological study during 2015-2019. A total of 964 RSV-positive specimens were identified from 5529 enrolled patients during a multi-center study. RSV subgroup A (RSV-A) was the predominant subgroup during this research period except in 2016. Totally, 535 sequences of the second hypervariable region (HVR-2) of the G gene were obtained. Combined with 182 Chinese sequences from GenBank, phylogenetic trees showed that 521 RSV-A sequences fell in genotypes ON1 (512), NA1 (6) and GA5 (3), respectively; while 196 RSV-B sequences fell in BA9 (193) and SAB4 (3). ON1 and BA9 were the only genotypes after December 2015. Genotypes ON1 and BA9 can be separated into 10 and 7 lineages, respectively. The HVR-2 of genotype ON1 had six amino acid changes with a frequency more than 10%, while two substitutions H258Q and H266L were co-occurrences. The HVR-2 of genotype BA9 had nine amino acid substitutions with a frequency more than 10%, while the sequences with T290I and T312I were all from 2018 to 2019. One N-glycosylation site at 237 was identified among ON1 sequences, while two N-glycosylation sites (296 and 310) were identified in the 60-nucleotide duplication region of BA9. To conclusion, ON1 and BA9 were the predominant genotypes in China during 2015-2019. For the genotypes ON1 and BA9, the G gene exhibited relatively high diversity and evolved continuously.

4.
J Pediatr (Rio J) ; 2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33592175

RESUMO

OBJECTIVE: To investigate the impact of recombinant human interferon α1b (rhIFNα1b) treatment in infants hospitalized with lower respiratory tract infections on subsequent wheezing. METHODS: The clinical data of infants (n=540) with viral pneumonia, wheezy bronchitis, or bronchiolitis hospitalized in 19 Chinese hospitals from June 2009 to June 2015 were retrospectively analyzed. The parameters relevant to wheezing episodes within the last year were collected by telephone and questionnaires. The rhIFNα1b treatment group (n=253) and control group (n=287) were compared in terms of wheezing episodes within the last year. Moreover, the wheezing group (95 cases) and non-wheezing group (445 cases) were compared. RESULTS: Out of 540 cases, 95 (17.6%) experienced wheezing episodes, 13.8% (35/253) cases treated with rhIFNα1b, and 20.9% (60/287) cases without rhIFNα1b experienced wheezing episodes within the last year. The rhIFNα1b treatment significantly improved wheezing episodes within the last year, compared with the control peers (p=0.031). Single-factor regression showed statistically significant differences between the wheezing and non-wheezing groups in terms of age, rhIFNα1b use, childhood and family history of allergy, housing situation, and feeding history (p<0.05). Binary logistic regression showed a childhood history of allergy (OR=2.14, p=0.004), no rhIFNα1b use (OR=1.70, p=0.028), and living in a crowded house (OR=1.92, p=0.012) might be risk factors of subsequent wheezing. Accordingly, breastfeeding (OR=0.44, p=0.008) and hospitalization age of ≤1-year-old (OR=0.58, p=0.024) were protective factors. CONCLUSIONS: Early use of rhIFNα1b in infants hospitalized with lower respiratory tract infections and breastfeeding could prevent subsequent wheezing. Living in a crowded house could promote subsequent wheezing.

5.
Virol Sin ; 36(3): 382-392, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33400092

RESUMO

To investigate the molecular epidemiology and genetic variation of human adenovirus type 7 (HAdV-7) in children with acute respiratory infections (ARI) in China. HAdV-7-positive respiratory samples collected from children with ARI in Beijing, Shijiazhuang, Wenzhou and Guangzhou from 2014-2018 were selected for gene amplification and sequence analysis. Fifty-seven HAdV-7 clinical strains with hexon, penton base and fiber gene sequences were obtained. Meanwhile 17 strains were selected randomly from different cities for whole genome sequencing. Phylogenetic and variation analyses were performed based on the obtained sequences, HAdV-7 prototype strain Gomen (AY594255), vaccine strains (AY495969 and AY594256) and representative sequences of strains. The phylogenetic trees constructed based on whole genome sequences, major capsid protein genes (hexon, penton base and fiber) and the early genes (E1, E2, E3 and E4) were not completely consistent. The HAdV-7 strains obtained in this study always clustered with most of the circulating strains worldwide from the 1980s to the present. Compared with the HAdV-7 prototype strain Gomen (AY594255), some amino acid mutations in loop1 and loop2 of hexon and the RGD loop region of the penton base gene were observed. Recombination analysis showed that partial regions of 55 kDa protein and 100 kDa hexon-assembly associated protein genes among all HAdV-7 strains in this study were from HAdV-16 and HAdV-3, respectively. Our study demonstrated the molecular evolution characteristics of HAdV-7 strains circulating in China and provided basic reference data for the prevention, control and vaccine development of HAdV-7.


Assuntos
Infecções por Adenovirus Humanos , Adenovírus Humanos , Infecções por Adenovirus Humanos/epidemiologia , Adenovírus Humanos/genética , Criança , China/epidemiologia , Evolução Molecular , Genoma Viral , Humanos , Filogenia , Análise de Sequência de DNA
6.
Front Pediatr ; 8: 543, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33014937

RESUMO

Mutations that affect the STING1 (TMEM173) gene cause a rare autoinflammatory syndrome, which is known as STING-associated vasculopathy with onset in infancy (SAVI) and which was initially described in 2014 (1). Thus far, only four reports have been conducted regarding families affected with SAVI in the literature. In this article, the clinical, laboratory, and genetic characteristics of two generations (three cases) of SAVI are described. Unlike previously reported cases that were caused by STING1 mutation, the initial and major clinical manifestations of the mentioned cases are largely identified in the lungs with interstitial lung disease (ILD), and the evidence of typical extrapulmonary symptoms of early-onset systemic inflammation (e.g., cutaneous vasculopathy) were minimal except for the proband, who was diagnosed with arthritis 8 years after onset. In addition, a younger sibling showed no symptoms. Such reports are rarely related to mutations in STING1. The proband was examined with bronchoscopy and alveolar lavage to determine the cause. This study emphasizes that, in the clinical assessment of interstitial pneumonia in children, the possibility of STING1 mutation should be considered, especially in patients with arthritis in addition.

7.
Exp Ther Med ; 16(2): 966-970, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30116346

RESUMO

Cysteinyl leukotriene receptor 1 (CYSLTR1) serves a pivotal role in allergic reactions, which is one of the main causes of adenoid hypertrophy. The present study aimed to investigate the function of CYSLT1 within adenoid hypertrophy. A total of 40 patients with adenoid hypertrophy were recruited between January 2014 and January 2016 at the Children's Hospital of Hebei Province, China. The patients were divided into either the mild-moderate group or the severe group according to their disease severity. The expression of CYSLT1 in the adenoid tissue and whole blood of all patients and healthy controls was detected by reverse transcription-quantitative polymerase chain reaction. Associations between the expression level of CYSLT1 and the clinical characteristics of patients were analyzed. Primary human adenoid epithelial cells (HAECs) with CYSLT1 knockdown and overexpression were constructed. The levels of extracellular signal-regulated kinase (ERK)2 and phosphorylated-ERK1/2 in adenoid tissue and HAECs were detected by western blot analysis. The expression of CYSLT1 in adenoid tissue and whole blood of all patients with adenoid hypertrophy was significantly higher compared with the healthy controls (P<0.05). In addition, the expression level of CYSLT1 was significantly higher in the severe group compared with the mild-moderate group (P<0.05). The highest level of p-ERK1/2 in adenoid tissue was observed in the severe group, followed by the mild-moderate group and then the control group (P<0.05). CYSLT1 expression was positively associated with the severity of disease. CYSLT1 knockdown significantly decreased the level of p-ERK1/2 in HAECs (P<0.05), while CYSLT1 overexpression significantly increased the level of p-ERK1/2. It was concluded that CYSLT1 may contribute to the progression of adenoid hypertrophy by activating ERK1/2.

8.
Sci Rep ; 8(1): 4491, 2018 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-29540836

RESUMO

To identify the variations in fusion (F) protein gene of RSV in China, a molecular epidemiological study was conducted. A total of 553 RSV positive specimens were collected from 2338 pediatric patients hospitalized with community-acquired pneumonia during a multi-center study conducted during 2014-2016. A total of 252 samples (183 RSV A, 69 RSV B) were selected for F gene sequencing, and analyzed together with 142 F gene sequences downloaded from GenBank. The result showed that all the Chinese RSV A and RSV B strains could be divided respectively into three branches. Compared with RSV A/B prototype sequences respectively, there were significant amino acid (AA) mutations at multiple antigenic sites. For RSV A, changes were found at AA residues 122, 124, 125, 276 and 384, and for RSV B at AA residues 45, 116, 125, 172, 173 and 202. Variations in human histocompatibility leukocyte antigen-restricted CTL epitopes were also observed. In total, 56 amino acid differences for the complete F protein were found between the RSV A and B groups in China, while several mutations were only found in the RSV B strains during 2015-2016. The RSV F gene is relatively conserved in China, however, limited mutations are still occurring with time.


Assuntos
Infecções Comunitárias Adquiridas/virologia , Variação Genética , Pneumonia Viral/virologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/genética , Proteínas Virais de Fusão/genética , Alelos , Criança , Pré-Escolar , China/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/imunologia , Epitopos de Linfócito T/imunologia , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Filogenia , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sincicial Respiratório Humano/imunologia , Vírus Sincicial Respiratório Humano/isolamento & purificação , Análise de Sequência de DNA , Linfócitos T Citotóxicos/imunologia , Proteínas Virais de Fusão/imunologia
9.
Zhongguo Dang Dai Er Ke Za Zhi ; 18(1): 51-4, 2016 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-26781413

RESUMO

OBJECTIVE: To investigate the distribution of respiratory viruses on throat swabs in hospitalized children with acute lower respiratory tract infection (ALRTI). METHODS: A total of 5,150 children with ALRTI who were admitted to Hebei Children's Hospital between March 2014 and February 2015 were enrolled to investigate the distribution of respiratory viruses in children with ALRTI. Direct immunofluorescence assay was performed for throat swabs from these children to detect influenza virus A (FA), influenza virus B (FB), adenovirus (ADV), respiratory syncytial virus (RSV), and parainfluenza virus types 1, 2, and 3 (PIV-1, PIV-2, and PIV-3). RESULTS: Of all the 5,150 throat swabs from hospitalized children, 2,155 (41.84%) had positive virus detection results. RSV had the highest detection rate (1,338 cases/25.98%), followed by PIV-3 (439 cases/8.52%) and FA (166 cases/3.22%), and 29 patients had mixed infection with 2 viruses. With the increasing age, the detection rates of viruses tended to decrease (χ2=279.623; P<0.01). The positive rate of RSV increased gradually from September, and reached the peak value (60.09%) in November; the lowest positive rate occurred in June (1.51%). The positive rate of PIV-3 was the highest in May (21.38%) and the lowest in November (1.77%). CONCLUSIONS: The distribution of viruses in children with ALRTI varies with age and season, with RSV prevalence in autumn and winter and PIV-3 prevalence in spring and summer. RSV is the most common viral pathogen that causes ALRTI in hospitalized children.


Assuntos
Infecções Respiratórias/virologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Orthomyxoviridae/isolamento & purificação , Vírus da Parainfluenza 3 Humana/isolamento & purificação , Vírus Sinciciais Respiratórios/isolamento & purificação , Estações do Ano
10.
Zhongguo Dang Dai Er Ke Za Zhi ; 17(5): 487-91, 2015 May.
Artigo em Chinês | MEDLINE | ID: mdl-26014701

RESUMO

OBJECTIVE: To investigate the clinical characteristics and treatment defects in slow-to-recover children with Mycoplasma pneumoniae pneumonia (MPP) associated with airway mucous plug formation, and to provide a basis for prognostic judgment and therapeutic guidance. METHODS: A retrospective analysis was performed on the clinical data of 67 children with MPP who were admitted between May 2012 and May 2014 and showed airway mucous plug formation in fiberoptic bronchoscope examinations. Based on the results of re-examinations using imaging methods, all patients were classified into a slow-to-recover group (n=30) and a control group (n=37). Comparisons of clinical outcomes, laboratory indices, imaging findings, and treatment methods were performed between the two groups. The receiver operating characteristic (ROC) curves were drawn to analyze the indices with significant differences. RESULTS: The percentage of neutrophils, levels of C-reactive protein (CRP), lactic dehydrogenase (LDH), fibrinogen (FIB), and IgM in peripheral blood, and incidence of pleural effusion were significantly higher in the slow-to-recover group than in the control group (P<0.05). The fever duration and treatment time of azithromycin and fiberoptic bronchoscope for the first time were significantly longer in the slow-to-recover group than in the control group (P<0.05). The results of ROC curve analysis showed that the optimal cut-off points of fever duration, percentage of neutrophils, levels of CRP and FIB, and treatment time of fiberoptic bronchoscope for the first time were 11.5 days, 70.7%, 57 mg/L, 4.7 g/L, and 13.5 days, respectively, with sensitivity and specificity higher than 0.643 and 0.727. CONCLUSIONS: The fever duration, percentage of neutrophils, level of CRP, level of FIB, and treatment time of fiberoptic bronchoscope for the first time can predict a recovery time longer than two months in children with MPP associated with mucous plug formation.


Assuntos
Obstrução das Vias Respiratórias/etiologia , Pneumonia por Mycoplasma/complicações , Broncoscopia , Proteína C-Reativa/análise , Criança , Pré-Escolar , Feminino , Fibrinogênio/análise , Humanos , Masculino , Neutrófilos , Pneumonia por Mycoplasma/sangue , Curva ROC , Estudos Retrospectivos
11.
Zhongguo Dang Dai Er Ke Za Zhi ; 17(4): 317-20, 2015 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-25919547

RESUMO

OBJECTIVE: To examine fractional exhaled nitric oxide (FeNO) values in 1-3-year-old children with asthma and analyze the correlation of FeNO with peripheral blood eosinophils (EOS) and lung function in these children. METHODS: A total of 111 children aged 1-3 years with asthma were enrolled. The children were classified into acute exacerbation (n=62) and remission groups (n=49) according to their symptoms. FeNO values, lung function, and peripheral blood EOS count were measured in these children. Sixty age-matched healthy children were enrolled as the control group. RESULTS: FeNO values were significantly higher in the acute exacerbation group (24.4 ppb) than in the remission group (18.0 ppb) and the control group (13.7 ppb) (P<0.05). The FeNO values in the remission group were significantly higher than in the control group (P<0.05). FeNO values were not significantly correlated with peripheral blood EOS count and lung function parameters (PEF, TEF25, TEF50, and TEF75). CONCLUSIONS: Measurement of FeNO is useful to evaluate the disease activity in children with asthma aged 1 to 3 years, but the FeNO values are not correlated with peripheral blood EOS count and lung function.


Assuntos
Asma/fisiopatologia , Testes Respiratórios , Eosinófilos/fisiologia , Pulmão/fisiopatologia , Óxido Nítrico/metabolismo , Asma/sangue , Pré-Escolar , Feminino , Humanos , Lactente , Masculino
12.
Zhongguo Dang Dai Er Ke Za Zhi ; 17(2): 134-7, 2015 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-25760836

RESUMO

OBJECTIVE: To study the utility of fractional exhaled nitric oxide (FeNO) in young children at different stages of asthma. METHODS: Fifty-eight children with newly diagnosed asthma (aged 1-3 years) at the acute exacerbation stage between April and June, 2014 were recruited. After 3 months' treatment, the children switched into the chronic persistent stage (n=34) or remission stage (n=24). Thirty aged-matched healthy children served as controls. FeNO levels and lung function were measured for all subjects. The best cut-off value of FeNO for the diagnosis of asthma was evaluated by receiver operating characteristic (ROC) curve. RESULTS: The FeNO levels in children with asthma at various stages were higher than controls (P<0.05). The FeNO levels in the acute exacerbation stage were highest, followed by the chronic persistent stage (P<0.05). FeNO level was correlated to the stages of asthma (r=-0.382, P<0.001). The cut-off value of FeNO for the diagnosis of asthma was 22.75 ppb by ROC curve, with the sensitivity of 0.933 and the specificity of 0.388. CONCLUSIONS: The children with asthma at different stages have different FeNO levels. Measurement of FeNO is useful in the diagnosis of asthma in young children.


Assuntos
Asma/diagnóstico , Testes Respiratórios , Óxido Nítrico/metabolismo , Asma/metabolismo , Humanos , Curva ROC
13.
Zhongguo Dang Dai Er Ke Za Zhi ; 15(3): 171-4, 2013 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-23498755

RESUMO

OBJECTIVE: To compare the conventional pulmonary function test results of children with asthma or cough variant asthma (CVA). METHODS: A total of 140 children, who were diagnosed with asthma or CVA from May 2010 to May 2011, were divided into acute asthma attack (n=50), asthma remission (n=50) and CVA groups (n=40); 30 healthy children were included as a control group. The forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), forced expiratory flow after 25% of vital capacity has been expelled (FEF25), forced expiratory flow after 50% of vital capacity has been expelled (FEF50), forced expiratory flow after 75% of vital capacity has been expelled (FEF75) and maximal midexpiratory flow (MMEF75/25) were measured. RESULTS: The mean percent predicted values of all the above indices were lower than 80% in the acute asthma attack group, with FEF50, FEF75 and MMEF75/25 declining markedly; the mean percent predicted values of FEF75 and MMEF75/25 were lower than 80% in the CVA group. All the pulmonary function indices in the acute asthma attack group were lower than those in the control group. The mean percent predicted values of FVC, FEV1, FEF25 and MMEF75/25 in the asthma remission and CVA groups were lower than in the control group. All the pulmonary function indices in the acute asthma attack group were lower than in the asthma remission and CVA groups, but there were no significant differences between the asthma remission and CVA groups. CONCLUSIONS: There is small and large airway dysfunction, particularly small airway dysfunction, in children with acute asthma attack. Children with CVA present mainly with mild small airway dysfunction, as do those with asthma in remission.


Assuntos
Asma/fisiopatologia , Tosse/fisiopatologia , Pulmão/fisiopatologia , Criança , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Capacidade Vital
15.
Zhongguo Dang Dai Er Ke Za Zhi ; 13(7): 547-50, 2011 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-21752319

RESUMO

OBJECTIVE: To evaluate the effectiveness of the flexible bronchoscopy in the diagnosis and treatment of refractory pneumonia among children. METHODS: Sixty children with refractory pneumonia were randomly divided into two groups: lavage and control (n=30 each). The control group received conventional medical treatment. The lavage group was given flexible bronchoscopy besides conventional medical treatment. The therapeutic effects were compared between the two groups. The results of bacterial culture and detection of antibodies against Mycoplasma pneumoniae in bronchoalveolar lavage fluid (BALF) were observed. RESULTS: The coincidence of bacterial culture results between BALF and sputum samples was 63.3%, and there were no significant differences in the positive bacterial culture results between them. The coincidence of PCR test for antibodies against Mycoplasma pneumoniae between BALF and serum samples was 73.3%. The results of Fisher's exact test showed the positive rate of Mycoplasma pneumoniae antibodies of BALF was higher than that of serum (P<0.05). The effective rate in the lavage group was significantly higher than that in the control group (97% vs 73%; P<0.01). CONCLUSIONS: The flexible bronchoscopy is useful for the diagnosis and treatment of refractory pneumonia in children.


Assuntos
Broncoscopia/métodos , Pneumonia/diagnóstico , Bactérias/isolamento & purificação , Líquido da Lavagem Broncoalveolar/microbiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pneumonia/terapia , Reação em Cadeia da Polimerase , Irrigação Terapêutica
16.
Zhonghua Xue Ye Xue Za Zhi ; 26(2): 82-5, 2005 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-15921623

RESUMO

OBJECTIVE: To explore the myelo-protection effect of mdr1 transfected cord blood cells (CBMNCs) graft against high-dose homoharringtonine leukemia-bearing severe combined immunodeficient (SCID) mice model. METHODS: Multidrug resistant (mdr1)gene was transferred into CBMNCs by a retrovirus vector, containing full-length cDNA of human mdr1 gene. CBMNCs and high-titer retrovirus supernatant were cocultured with cytokine combinations for 5 - 6 days. The SCID mouse models bearing human HL-60 cell leukemia were divided into three groups. Group A received tail vein injection of 2 x 10(6) mdr1 gene transduced CBMNCs at day 1 and 3, groups B and C 2 x 10(6) un-transduced CBMNCs and same volume of normal saline, respectively. The 3 groups of the mouse model were treated with weekly escalated doses of homoharringtonine. The peripheral white blood cell (WBC) counts, the human leukemia cells percentage in peripheral blood, the histological findings of main organs were assayed. The CD33 positive HL-60 cells in bone marrow were determined by flow cytometry. The function and expression of mdr1 gene were examined by PCR, immunochemistry (IC) and DNR extrusion test in vivo. RESULTS: (1) mdr1 gene was transferred into CBMNCs successfully and the transfection frequency was 30%. (2) Leukemia SCID mice were xenotransplanted with mdr1-transfected BMMNCs by a programmed procedure and could be used as a valuable model for in vivo evaluating myelo-protection effects. (3) The transfected mice could tolerate homoharringtonine 5 approximately 6 folds higher than conventional dose and kept peripheral WBC count at a mean of 3 x 10(9)/L, with the peripheral human myeloid leukemia cells percentage decreasing to less than 5%. Histological examination showed that there was no leukemia infiltration in the main organs, the CD33 positive HL-60 cells in bone marrow were less than 5%. (4) The repopulation frequency of the transfected CBMNs in marrow were 9.13%. DNR extrusion test confirmed that the P-gp product maintained its biological function in the marrow. CONCLUSION: mdr1 transferred-human CBMNC can xenotransplanted and repopulated in leukemia-bearing SCID mouse and are protected from chemotherapy-induced myelosuppression.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Sangue Fetal/citologia , Harringtoninas/uso terapêutico , Leucemia Promielocítica Aguda/cirurgia , Leucócitos Mononucleares/transplante , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/uso terapêutico , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Feminino , Vetores Genéticos , Células HL-60 , Harringtoninas/administração & dosagem , Harringtoninas/efeitos adversos , Mepesuccinato de Omacetaxina , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/patologia , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/metabolismo , Masculino , Camundongos , Camundongos SCID , Distribuição Aleatória , Retroviridae/genética , Transfecção , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Zhonghua Xue Ye Xue Za Zhi ; 23(8): 400-2, 2002 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-12411041

RESUMO

OBJECTIVE: To investigate the expression of mdr1 gene in hematopoietic cells of a murine bone marrow transplantation model and to explore the feasibility of transferring mdr1 gene into hematopoietic cells to pro-vent myelosuppression from chemotherapy. METHODS: mdr1 gene was transferred into hematopoietic cells of murine bone marrow by retrovirus vector. The expression and function of mdr1 gene in vivo was tested in a murine bone marrow transplantation model. RESULTS: (1) mdr1 gene was successfully transferred into murine MNC, the transduction rate was 35%. (2) mdr1 gene transferred murine bone marrow transplantation model was established successfully by scheduled-bone marrow transplantation method. (3) In 1 approximately 5 months period, stable and effective expression of mdr1 gene could be detected in hematopoietic cells of the recipient mouse, the percentage of mdr1 gene expression cells in recipient's hematopoietic cells decreased monthly to 8.0%, 8.0%, 7.5%, 4.0% and 3.0%. (4) mdr1 expression hematopoietic cells had efficient resistance to chemotherapy. CONCLUSION: It is an effective approach to transfer mdr1 gene into hematopoietic cells for preventing myelosuppression in chemotherapy.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Transplante de Medula Óssea , Células-Tronco Hematopoéticas/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Antibióticos Antineoplásicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Daunorrubicina/farmacologia , Resistência a Múltiplos Medicamentos , Expressão Gênica , Vetores Genéticos/genética , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Contagem de Leucócitos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Paclitaxel/farmacologia , Retroviridae/genética , Transfecção
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