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2.
Eur J Pharmacol ; 895: 173888, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33493484

RESUMO

To explore the potential targets underlying the effect of rosuvastatin on heart failure (HF) by utilizing a network pharmacology approach and experiments to identify the results. PharmMapper and other databases were mined for information relevant to the prediction of rosuvastatin targets and HF-related targets. Then, the rosuvastatin-HF target gene networks were created in Cytoscape software. Eventually, the targets and enriched pathways were examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Furthermore, we constructed an HF animal model and used rosuvastatin to treat them, identifying the changes in heart function and related protein expression. We further used different cells to explore the mechanisms of rosuvastatin. Thirty-five intersection targets indicated the therapeutic targets linked to HF. GO analysis showed that 481 biological processes, 4 cellular components and 23 molecular functions were identified. KEGG analysis showed 13 significant treatment pathways. In animal experiments, rosuvastatin significantly improved the cardiac function of post-myocardial infarction mice and prevented the development of HF after myocardial infarction by inhibiting IL-1Β expression. Cell experiments showed that rosuvastatin could reduce the expression of IL-1B in HUVEC and THP-1 cells. The therapeutic mechanism of rosuvastatin against HF may be closely related to the inhibition of the expression of apoptosis-related proteins, inflammatory factors, and fibrosis-related genes. However, IL-1Β is one of the most important target genes.


Assuntos
Fármacos Cardiovasculares/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Rosuvastatina Cálcica/farmacologia , Animais , Bases de Dados Genéticas , Modelos Animais de Doenças , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Mapas de Interação de Proteínas , Transdução de Sinais , Células THP-1 , Transcriptoma
3.
Clin Auton Res ; 30(6): 521-530, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32761450

RESUMO

PURPOSE: To perform a comprehensive meta-analysis of all available evidence on the efficacy and safety of catheter-based renal denervation for heart failure with reduced ejection fraction. METHODS: We searched English and Chinese databases and calculated the weighted mean difference or standardized mean difference and 95% confidence intervals to estimate the efficacy and safety of renal denervation for heart failure. All relevant studies were screened and a meta-analysis was conducted using Review Manager 5.4. RESULTS: A total of 11 studies were identified for the meta-analysis. For the primary outcomes, the results showed that renal denervation significantly improved ejection fraction (weighted mean difference 6.42), left ventricular end-systolic diameter (weighted mean difference -3.95), left ventricular end-diastolic diameter (weighted mean difference -4.17) and left atrial diameter (weighted mean difference -4.09). For the secondary outcomes, renal denervation reduced the B-type natriuretic peptide level, heart rate, systolic blood pressure and diastolic blood pressure. However, further analysis revealed that renal denervation improved heart function but did not further reduce the heart rate and blood pressure compared with the control group. CONCLUSION: Treatment with renal denervation can significantly improve heart function and structure in patients with heart failure. In addition, the level of B-type natriuretic peptide can be reduced after renal denervation treatment. Renal denervation did not further reduce heart rate and blood pressure compared with the control group. Therefore, the treatment of heart failure with renal denervation is effective and safe.


Assuntos
Insuficiência Cardíaca , Simpatectomia , Pressão Sanguínea , Cateteres , Insuficiência Cardíaca/cirurgia , Humanos , Rim/cirurgia
4.
Am J Physiol Heart Circ Physiol ; 318(6): H1525-H1537, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32383996

RESUMO

Growing evidence shows that activation of inflammation in the heart provokes left ventricular (LV) remodeling and dysfunction in humans and experimental animals with heart failure (HF). Moreover, recent studies found that cyclic GMP-AMP synthase (cGAS), serving as a cytosolic DNA sensor, was essential for activating innate immunity against infection and cellular damage by initiating the STING-IRFs-type I IFN signaling cascade, which played important roles in regulating the inflammatory response. However, the pathophysiological role of cGAS in pressure overload-induced HF is unclear. Wild-type C57BL/6J mice and cGAS inhibition mice were subjected to transverse aortic constriction (TAC) to induce HF or sham operation. Inhibition of cGAS in the murine heart was performed using adeno-associated virus 9 (AAV9). Alterations of the cGAS/STING pathway were examined by qPCR and Western blotting. Cardiac remodeling was assessed by echocardiography as well as histological and molecular phenotyping. Compared with sham-operated mice, the cGAS/STING pathway was activated in LV tissues in TAC mice. Whereas TAC mice exhibited significant pathological cardiac remodeling and LV dysfunction, inhibition of cGAS improved early survival rates after TAC, preserved LV contractile function, and blunted pathological remodeling, including cardiac hypertrophy, fibrosis, and apoptosis. Furthermore, downregulation of cGAS diminished early inflammatory cell infiltration and inflammatory cytokine expression in response to TAC. These results demonstrated that cGAS played an essential pathogenetic role in pressure overload-induced HF to promote pathological cardiac remodeling and dysfunction. Our results suggest that inhibition of cGAS may be a novel therapeutic approach for HF.NEW & NOTEWORTHY In this study, we first revealed a novel role of cGAS in the regulation of pathological cardiac remodeling and dysfunction upon pressure overload. We found that the cGAS/STING pathway was activated during pressure overload. Moreover, we also demonstrated that inhibition of the cGAS/STING pathway alleviated pathological cardiac remodeling and downregulated the early inflammatory response during pressure overload-induced HF. Together, these findings will provide a new therapeutic target for HF.


Assuntos
Pressão Sanguínea/fisiologia , Insuficiência Cardíaca/metabolismo , Proteínas de Membrana/metabolismo , Nucleotidiltransferases/metabolismo , Remodelação Ventricular/fisiologia , Animais , Coração/fisiopatologia , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/fisiopatologia , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Transgênicos , Nucleotidiltransferases/genética , Transdução de Sinais
5.
World J Pediatr ; 16(3): 232-239, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32333248

RESUMO

In the early February, 2020, we called up an experts' committee with more than 30 Chinese experts from 11 national medical academic organizations to formulate the first edition of consensus statement on diagnosis, treatment and prevention of coronavirus disease 2019 (COVID-19) in children, which has been published in this journal. With accumulated experiences in the diagnosis and treatment of COVID-19 in children, we have updated the consensus statement and released the second edition recently. The current version in English is a condensed version of the second edition of consensus statement on diagnosis, treatment and prevention of COVID-19 in children. In the current version, diagnosis and treatement criteria have been optimized, and early identification of severe and critical cases is highlighted. The early warning indicators for severe pediatric cases have been summarized which is utmost important for clinical practice. This version of experts consensus will be valuable for better prevention, diagnosis and treatment of COVID-19 in children worldwide.


Assuntos
Infecções por Coronavirus , Coronavirus , Pandemias , Pneumonia Viral/epidemiologia , Betacoronavirus , COVID-19 , Criança , Consenso , Humanos , SARS-CoV-2
6.
Biosci Rep ; 39(11)2019 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-31661113

RESUMO

BACKGROUND: Previous studies have explored associations between interleukin-18 (IL-18) promoter polymorphisms and coronary artery disease (CAD). However, the results were controversial. We conducted a meta-analysis to clarify the association between the two polymorphisms and CAD risk. METHODS: We searched English and Chinese databases and calculated the odds ratio (OR) and 95% confidence interval (CI) to estimate whether there are genetic associations between IL-18 promoter polymorphisms and the risk of CAD. All relevant studies were screened and meta-analyzed using STATA 15.0. RESULTS: A total of 15 studies, including 12 studies for -137 G/C and 9 studies for -607 C/A, were identified for the meta-analysis. For -137 G/C, the results showed a significantly reduced risk of CAD in the dominant model (OR = 0.85) and heterozygous model (OR = 0.88) in the overall analysis. However, in subgroup analysis, decreased CAD risks were only observed in Asian populations for heterozygous genetic models. For -607 C/A, the overall OR revealed a reduced risk of CAD in all five genetic models (allelic, OR = 0.78; recessive, OR = 0.75; dominant, OR = 0.68; homozygous, OR = 0.61; heterozygous, OR = 0.72). In subgroup analysis, reduced CAD risk was also found in five genetic models of the Asian population. We also found that the IL-18 polymorphisms were correlated with myocardial infarction (MI) and multivessel (MV) disease. CONCLUSION: Our results suggested that the -137 polymorphism and -607 polymorphism in the IL-18 promoter were negatively associated with CAD, especially in the Asian population. In addition, some genetic models were correlated with the severity of CAD.


Assuntos
Doença da Artéria Coronariana/genética , Predisposição Genética para Doença/genética , Interleucina-18/genética , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Alelos , Estudos de Casos e Controles , Heterozigoto , Humanos , Razão de Chances
7.
Psychol Health Med ; 24(1): 51-58, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29695175

RESUMO

Low well-being is common among Chinese pregnant women but few effective interventions currently exist to improve prenatal stress and negative emotions. Mindfulness-based stress reduction (MBSR) has been proved to be effective in reducing stress and rarely studies were focused on Chinese pregnant women. The aim of the current paper is to investigate the effects of 8-week MBSR on prenatal stress, anxiety and depression among Chinese pregnant women. A sample of 66 pregnant women randomly allocated into either the MBSR group (n=34) or the control group (n=32). Participants in the MBSR group received a group 8-week, 90-min each time intervention. The results found a significant interaction between time and condition for prenatal stress (F=45.51, p<0.001, η 2=0.427), anxiety (F=19.30, p<0.001, η 2=0.240), while depression showed no time-by-group interaction (F=0.29, p=0.589, η 2=0.005). As for the sub-scale of state anxiety, while there was only no time effect (F=3.68, p=0.060, η 2=0.057). The findings of this study preliminary indicated effects of the MBSR intervention on self-reported prenatal stress and anxiety in comparison to a treatment-as-usual control. Effect on depression was not observed may due to the low level of depression of participants. This study provides preliminary evidence that MBSR is suitable for Chinese pregnant women and be effective in decreasing prenatal stress, anxiety.


Assuntos
Ansiedade/terapia , Depressão/terapia , Atenção Plena/métodos , Complicações na Gravidez/terapia , Estresse Psicológico/terapia , Adulto , Feminino , Humanos , Gravidez , Resultado do Tratamento , Adulto Jovem
8.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(6): 461-464, 2018 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-29972119

RESUMO

OBJECTIVE: To study the association of vitamin D level with asthma control and pulmonary function in children with asthma. METHODS: A total of 150 children with asthma were enrolled as observation group, and 55 healthy children were enrolled as control group. According to the level of asthma control, the children were divided into good control group, partial control group, and non-control group. Chemiluminescence microparticle immunoassay was used to measure the serum level of 25-hydroxyvitamin D [25(OH)D] for all groups. According to the level of 25(OH)D, the asthmatic children were divided into normal vitamin D group, vitamin D insufficiency group, and vitamin D deficiency group. Pulmonary function was measured for all asthmatic children. RESULTS: The observation group had a significantly lower serum level of 25(OH)D than the control group (25± 7 ng/mL vs 29± 4 ng/mL; P<0.05). The normal vitamin D group had the highest asthma control rate, followed by the vitamin D insufficiency group and the vitamin D deficiency group (P<0.05). There was no significant difference in pulmonary function among the three groups (P>0.05). CONCLUSIONS: Asthmatic children have a lower serum level of 25(OH)D than healthy children. The serum level of 25(OH)D is associated with the level of asthma control and has no association with pulmonary function.


Assuntos
Asma/sangue , Pulmão/fisiopatologia , Vitamina D/sangue , Asma/fisiopatologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino
10.
Zhongguo Dang Dai Er Ke Za Zhi ; 19(11): 1174-1179, 2017 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-29132465

RESUMO

OBJECTIVE: To investigate the significance of flexible bronchoscopy in children with respiratory diseases. METHODS: A retrospective analysis was performed for the clinical data of 80 children who were hospitalized due to respiratory diseases (including severe pneumonia, Mycoplasma pneumoniae pneumonia with atelectasis/lung consolidation/local emphysema, protracted pneumonia, coughing and wheezing of unknown cause, chronic cough of unknown cause, and laryngeal stridor) and who underwent flexible bronchoscopy/alveolar lavage. RESULTS: Bronchoscopy found that all the 80 children had endobronchial inflammation, among whom 28 children had severe airway obstruction by secretion. Twenty-four children had congenital airway dysplasia besides endobronchial inflammation, and three children had bronchial foreign bodies. In the children with coughing and wheezing of unknown cause and laryngeal stridor, some had congenital airway dysplasia or bronchial foreign bodies. Among the 27 children with Mycoplasma pneumoniae pneumonia, 26 had severe airway obstruction/embolization by secretion; 25 children (93%) underwent chest imaging again at 2 weeks after alveolar lavage, and the results showed complete or partial lung recruitment. Among the 80 children who underwent bronchoscopy, 3 had severe hypoxemia during surgery, 1 had epistaxis, 1 had minor bleeding during alveolar lavage, 3 had transient bronchospasm, and 5 had postoperative fever; these children were all improved after symptomatic treatment. CONCLUSIONS: Flexible bronchoscopy is safe and reliable in children with respiratory diseases. Early alveolar lavage under a flexible bronchoscope is recommended for children with severe/refractory Mycoplasma pneumoniae pneumonia to improve prognosis. Flexible bronchoscopy is recommended for children with recurrent coughing and wheezing and persistent laryngeal stridor, in order to directly observe the throat and airway under an endoscope.


Assuntos
Broncoscopia/métodos , Pneumopatias/diagnóstico , Broncoscopia/efeitos adversos , Criança , Pré-Escolar , Tosse/diagnóstico , Feminino , Humanos , Lactente , Masculino , Pneumonia por Mycoplasma/diagnóstico , Sons Respiratórios/diagnóstico , Estudos Retrospectivos
11.
J Geriatr Cardiol ; 14(6): 401-406, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29056947

RESUMO

OBJECTIVE: To study prognostic characteristics of cardiac troponin I (cTnI) elevation in acute ischemic stroke. METHODS: We retrospectively studied patients (n = 248) with acute ischemic stroke, acute ST-segment elevation myocardial infarction, and acute non-ST-elevation myocardial infarction who were treated between January 2013 and October 2015. Baseline demographic data and changes in cTnI levels among these three groups were compared. Patients with acute ischemic stroke were assigned to either the cTnI elevation group (cTnI > 0.034 ng/mL) or the no cTnI elevation group (cTnI ≤ 0.034 ng/mL). Logistic regression analysis was used to identify risk factors associated with elevated serum cTnI in patients with acute ischemic stroke. Moreover, the duration of hospital stay and incidence of major cardiovascular outcomes were compared in patients with acute ischemic stroke, with or without elevated cTnI. RESULTS: In this study population of patients with acute ischemic stroke (n = 178), acute ST-segment elevation myocardial infarction (n = 35), and acute non-ST-elevation myocardial infarction (n = 35), patients with acute ischemic stroke with elevated cTnI comprised 18.5% of subjects. Patients with elevated cTnI were older and more likely to have a history of hypertension. In addition, these patients had higher levels of inflammatory markers, reduced renal functions, increased D-dimer levels, higher NIH stroke scores, and lower left ventricular ejection fractions. Logistic regression analysis showed that both percentage of neutrophil and NIH stroke scores were elevated; estimated glomerular filtration rate and left ventricular ejection fraction were decreased in patients with acute ischemic stroke who had elevated cTnI, and they had more frequent major cardiovascular events during hospital stay. CONCLUSION: Elevated cTnI detected in patients with acute ischemic stroke, indicated a greater likelihood of poor short-term prognosis during hospital stay.

12.
Zhongguo Dang Dai Er Ke Za Zhi ; 19(7): 796-799, 2017 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-28697834

RESUMO

OBJECTIVE: To investigate the association of serum vitamin D [25-(OH)D3] level with the severity and treatment in children with Henoch-Schönlein purpura (HSP). METHODS: A total of 50 children with newly-diagnosed HSP between January and December, 2015 were enrolled as HSP group, and 49 healthy children were enrolled as control group. Fasting serum samples were collected, and ELISA was used to measure serum 25-(OH)D3 level. According to the serum 25-(OH)D3 level, the HSP group were further divided into normal group (>20 ng/mL) (n=9), insufficiency group (15-20 ng/mL) (n=15), deficiency group (≤15 ng/mL) (n=25), and severe deficiency group (≤5 ng/mL) (n=1). The general data, clinical manifestations, hormone therapy, course of disease before admission, and length of hospital stay were compared between groups. RESULTS: The HSP group had a significantly lower serum 25-(OH)D3 level than the control group (16±6 ng/mL vs 29±5 ng/mL; P<0.01). Compared with the normal and insufficiency groups, the deficiency and severe deficiency groups had significant increases in the incidence rate of renal involvement, rate of hormone application, and median length of hospital stay (P<0.05), while there was no significant difference in course of disease before admission (P>0.05). CONCLUSIONS: Children with HSP have a low serum 25-(OH)D3 level, and such children may have a high risk of renal involvement, a high rate of hormone application, and a prolonged length of hospital stay. However, further studies are needed to investigate whether vitamin D supplementation is helpful to the treatment of HSP and can shorten the course of disease in children with HSP.


Assuntos
/sangue , Vitamina D/análogos & derivados , Criança , Feminino , Humanos , /tratamento farmacológico , Tempo de Internação , Masculino , Índice de Gravidade de Doença , Vitamina D/sangue
13.
Int J Clin Exp Pathol ; 10(8): 9073-9083, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-31966780

RESUMO

BACKGROUND: Chest pain is a typical presentation in the emergency department (ED), often due to acute coronary syndrome. Accurate and fast identification is crucial. The diagnosis and proper treatment of unstable angina (UA) can reduce the chance of acute myocardial infarction, and reduce high mortality and morbidity rates. However there is a lack of reliable and valid biomarkers in the diagnosis of UA. This study investigated the usefulness of circulating microRNAs (miRNAs) for differentiating UA from non-ischemic chest pain (NICP) in the ED. Methods The expressions of circulating miRNAs in patients with UA were evaluated relative to individuals with NICP (control subjects). Circulating miR-21, miR-25, miR-92a, miR-106b, miR-126* and miR-451 levels were measured in 98 patients with UA and 95 control subjects in the ED. To investigate the underlying functions of miRNAs in UA, bioinformatic analysis of validated miRNAs was conducted. RESULTS: Circulating miRNAs were upregulated in UA compared with the control group. The combination of the modified HEART score (m-HS) and miR-25 (AUC 0.901, NRI 0.096) could better distinguish UA than m-HS alone. Bioinformatic analysis indicated that miRNAs may take part in platelet activation, cGMP-PKG signaling pathways etc. Conclusion: The circulating levels of miRNAs (miR-21, miR-25, miR-106b, miR-126*) are significantly higher in UA patients compared with patients with NICP, and the addition of the m-HS that combined ECG, age, risk factors and troponin is useful to detect or rule out UA. The associated signaling pathways are involved in the pathogenesis of vulnerable plaque.

14.
Environ Toxicol Pharmacol ; 40(3): 671-7, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26407229

RESUMO

Primary neuron cultures were established from the brains of neonatal rats and the effects of arsenic trioxide (As2O3) on the migration of neurons and the potential mechanism of As2O3 were investigated. Boyden chamber assay was used to detect the effect of AS2O3 on neuronal migration. Matrix metalloproteinase-2 (MMP-2) and MMP-9 RNA expression and doublecortin (DCX) protein expression were measured. Neuronal migration ability was significantly lower in the 20 µmol/L group compared with the other three groups (all p < 0.001). The expression of both MMP-2 and MMP-9 was significantly inversely correlated with As2O3 concentration. The expression of DCX was significantly higher in the control group compared with the other three groups (all p ≤ 0.003). Thus, the inhibitory effect of As2O3 on the migration of primary neurons might be related to the reduction in MMP-2 and MMP-9 activities and decrease in ß-actin and DCX expression.


Assuntos
Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Proteínas Associadas aos Microtúbulos/genética , Neurônios/efeitos dos fármacos , Neuropeptídeos/genética , Óxidos/toxicidade , Animais , Animais Recém-Nascidos , Trióxido de Arsênio , Arsenicais/administração & dosagem , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas In Vitro , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Neuropeptídeos/metabolismo , Óxidos/administração & dosagem , Ratos
15.
Am J Rhinol Allergy ; 28(2): 131-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24717951

RESUMO

BACKGROUND: Sublingual immunotherapy (SLIT) is recommended for allergic diseases. However, clinical studies containing evidence-based data of this treatment in young children, which is rarely reported in the literature, are needed. This study was designed to assess the efficacy and safety of SLIT in children, including very young children. METHODS: Two hundred sixty-four children aged 3-13 years old (133 children, 3-5 years old) with Dermatophagoides farinae-induced allergic rhinitis with or without asthma treated by standard pharmacotherapy had randomly received either SLIT (SLIT group) or no SLIT (control group) for 12 months. Symptoms, medications, visual analog scale (VAS) and presence of adverse events (AEs) were assessed at monthly visits. Skin-prick test and Dermatophagoides farinae-specific IgE and IgG4 were measured before and after treatment. RESULTS: Both treatments were effective in the global clinical scores during the first seven visits when compared with baseline (all, p < 0.01), and SLIT showed lower symptoms scores and VAS scores throughout this period (all, p < 0.01). These improvements continued until the later visits only in the SLIT group. Also, the asthma medication consumption was decreased by SLIT treatment only at the end of study (p < 0.01). The specific IgG4 was significantly increased after SLIT treatment when compared with the control group, but no significant change of specific IgE was observed in either groups. In the SLIT group, there was no significant difference between children less than or more than 5 years old in terms of clinical efficacy, onset of action, immunologic parameters, and safety. No severe systemic AEs were reported. CONCLUSION: SLIT is effective and well-tolerated in children with allergic rhinitis 3-13 years old.


Assuntos
Antígenos de Dermatophagoides/administração & dosagem , Asma/terapia , Dessensibilização Imunológica/métodos , Rinite Alérgica/terapia , Administração Sublingual , Adolescente , Animais , Antígenos de Dermatophagoides/efeitos adversos , Asma/complicações , Asma/imunologia , Criança , Pré-Escolar , Dermatophagoides farinae/imunologia , Feminino , Seguimentos , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Masculino , Rinite Alérgica/complicações , Rinite Alérgica/imunologia , Testes Cutâneos , Resultado do Tratamento
16.
Zhonghua Er Ke Za Zhi ; 51(1): 64-8, 2013 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-23527934

RESUMO

OBJECTIVE: Omenn syndrome is a rare autosomal recessive hereditary severe combined immunodeficiency. The purpose of this study was to understand clinical characteristics and genetic mutation type of Omenn syndrome and to improve the recognition of Omenn syndrome among pediatric clinicians. METHOD: One suspected case of severe combined immunodeficiency was found to have pneumonia repeatedly, intractable diarrhea, poor antibiotic treatment effect, lymphadenopathy, hepatosplenomegaly and erythroderma. The patient was diagnosed as having Omenn syndrome by RT-PCR, and the expression of RAG1/RAG2 and gene analysis of RAG1/RAG2 were performed. RESULT: The classification of lymphocyte was CD3(+) cells (35.3%), CD19(+) cells (0.4%), CD16(+) cells (57.6%). After stimulation with phytohemagglutinin (PHA), lymphocyte proliferation of the child was extremely low. Genetic studies showed RAG1 homozygous deletion mutation (2302 del T). He had detectable activated T-lymphocytes with low circulating B-lymphocytes and no evidence of maternal T-cell engrafment as indicated by the short tandem repeat (STR) analysis. CONCLUSION: Omenn syndrome is a severe combined immunodeficiency disease caused by mutations in the RAG1/RAG2 gene. The disease has been reported rarely in China. The clinical manifestations of the disease is early postnatal repeated infections and erythroderma. Mutation analysis of RAG1/RAG2 gene may help to confirm the diagnosis and may be useful in early immune reconstitution and genetic counseling.


Assuntos
Proteínas de Ligação a DNA/genética , Proteínas de Homeodomínio/genética , Mutação , Proteínas Nucleares/genética , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/genética , Sequência de Aminoácidos , Biomarcadores/sangue , Análise Mutacional de DNA , Genótipo , Humanos , Lactente , Linfócitos/imunologia , Linfócitos/patologia , Masculino , Repetições de Microssatélites , Fenótipo , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Imunodeficiência Combinada Severa/patologia
17.
Eur J Pharm Biopharm ; 84(3): 505-16, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23376242

RESUMO

Targeting of intracerebral functional regions has been limited by the inability to transport drugs across the blood-brain barrier (BBB) and by poor accumulation in these regions. To overcome these hurdles, liposomes modified with P-aminophenyl-α-d-mannopyranoside (MAN) were used as a fluorescent dye carrier through the BBB and used the specific distribution of liposomes (LIP) modified with MAN (MAN-LIP) to target various functional regions of the brain. An in vitro BBB model was established to evaluate the transendothelial ability of MAN-LIP, and liposomes uptake by C6 glioma cells was analyzed by flow cytometry and live cell imaging. Liposome targeting was evaluated using in vivo and ex vivo imaging. After MAN-LIP administration, the transendothelial ability and the delivery of fluorescent dye to the brain significantly increased. MAN-LIP concentrated in the cortex at 4 h, shifting distribution to the cerebellum and brainstem at 12 h. The fluorescence intensity in the hippocampus and pontine nuclei remained high and stable over a period of 12 h. The results demonstrate that MAN-LIP is able to enhance cellular uptake in vitro and also promotes penetration through the BBB and accumulation in the brain with a distinct spatio-temporal pattern.


Assuntos
Compostos de Anilina/química , Encéfalo/fisiologia , Portadores de Fármacos , Lipossomos/química , Manosídeos/química , Animais , Barreira Hematoencefálica , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Meios de Cultura/química , Endocitose , Citometria de Fluxo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Fatores de Tempo
18.
Pediatr Allergy Immunol ; 22(5): 482-7, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21771083

RESUMO

Omenn syndrome (OS) is a rare autosomal recessive genetic disorder and presents symptoms of severe combined immunodeficiency characterized by erythrodermia, eosinophilia, hepatosplenomegaly, lymphadenopathy, and elevated serum IgE levels. OS has been found to be caused by mutations in RAG1 or RAG2 gene that result in partial V(D)J recombination activity. No study on OS has been reported in Chinese children so far. In this study, the genotype and phenotypes of three infants with OS from three unrelated Chinese families were investigated. All the three children had most of the characteristics of OS except normal serum IgE level. Compound heterozygosity mutations in RAG1 gene (1983 G>A; 2444 C>T and 2219 C>T; 3127 C>G) were identified in two cases, and a homozygous deletion mutation with a premature stop codon was found at residue 2302 of RAG1 gene (2302delT, I729X) in the remaining case, including three novel mutations (2302delT, I729X; 2219 C>T, R699W; and 3127 C>G, Y1001X). Spectratyping analysis of T-cell receptor ß-chain variable region (TCRVß) gene rearrangement was performed in case 1 and case 2. All the 25 TCRVß subfamilies presented monoclonal or oligoclonal peaks in case 1 and 11 TCRVß subfamilies were very weak or even absent in case 2. This was the first report about OS in Chinese children. Molecular genetic testing represents an important tool for early confirmed diagnosis and may allow accurate carrier detection and prenatal diagnosis.


Assuntos
Genes RAG-1/genética , Mutação , Imunodeficiência Combinada Severa/genética , Imunodeficiência Combinada Severa/fisiopatologia , /genética , Análise Mutacional de DNA , Proteínas de Ligação a DNA/genética , Evolução Fatal , Genótipo , Heterozigoto , Proteínas de Homeodomínio/genética , Homozigoto , Humanos , Lactente , Recém-Nascido , Masculino , Proteínas Nucleares/genética , Fenótipo , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/patologia
19.
J Hazard Mater ; 162(2-3): 1135-40, 2009 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-18614282

RESUMO

Adsorption kinetics and adsorption isotherms of Cu(II) onto a nanosized hydroxyapatite (HAP) in the absence and presence of different low-molecular-weight organic acids are studied in batch experiments. The results show that the adsorption kinetics of Cu(II) onto the HAP are best described by pseudo-second-order model, and the adsorption isotherms of Cu(II) onto the HAP fit Dubinin-Radushkevich model very well with high correlation coefficient (R(2)=0.97-0.99). The amount adsorbed of Cu(II) onto the HAP at pH 5.5 was much higher than that at pH 4.5. The presence of organic acids significantly decreased the adsorption quantity of Cu(II), clarifying the lower sorption affinities of Cu(II)-organic acid complexes onto the HAP rather than Cu(II) ion. The decreased maximal adsorption quantity of Cu(II) onto the HAP increased with the increasing logarithm of cumulative formation constants of Cu(II) and organic acids. The stronger coordination of organic acid with Cu(II), the more decreased Cu(II) adsorption quantity onto the HAP.


Assuntos
Ácidos/química , Cobre/química , Durapatita/química , Nanopartículas Metálicas , Adsorção , Peso Molecular , Compostos Orgânicos/química , Termodinâmica
20.
Zhongguo Dang Dai Er Ke Za Zhi ; 11(12): 964-6, 2009 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-20113598

RESUMO

OBJECTIVE: To investigate the distribution and the antibiotic susceptibility of pathogenic bacteria in children from Guiyang with lower respiratory infection (LRI). METHODS: The nasopharyngeal aspirate samples were obtained from 893 hospitalized children with LRI between August 2006 and June 2008. An antibiotic susceptibility test was performed using the VITEK system and the Kirby-Bauer diffuse method after bacteria were identified. RESULTS: Five hundred and forty-three patients (60.8%) were bacteria-positive. A total of 598 strains (30 kinds of bacteria) were obtained from the sputum samples. Of them, 533 strains (89.1%) were gram-negative and 57 were gram-positive (9.8%). Escherichia coli (E. coli) and Kleb-siella pneumoniae (K. pneumoniae) were common in gram-negative strains. They were susceptive to piperacillin/tazobactam, amikacin, ciprofloxacin, and levofloxacin, especially to imipenem. Streptococcus pneumoniae (S. pneumoniae) and Stapthylococcus aureus (S. aureus) were common in gram-positive strains. S. pneumoniae was susceptive to penicillin and cefazolin sodium, but S. aureus was resistant. Both were high susceptive to vancomycin, and resistant to roxithromycin. CONCLUSIONS: Gram-negative bacteria are the main pathogens in children from Guiyang with LRI, and E. coli and K. pneumoniae are common. The antibiotic susceptibility of pathogenic bacteria varies with different strains of bacteria. A reasonable selection of antibiotics should be based on the antibiotic susceptibility test.


Assuntos
Bactérias/efeitos dos fármacos , Infecções Respiratórias/microbiologia , Adolescente , Criança , Pré-Escolar , Farmacorresistência Bacteriana , Feminino , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Nasofaringe/microbiologia
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