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1.
Artigo em Inglês | MEDLINE | ID: mdl-34593311

RESUMO

OBJECTIVE: This study aimed to compare the effects of nasal high-frequency oscillatory ventilation (NHFOV) and noninvasive positive-pressure ventilation (NIPPV) as the initial postextubation therapies on preventing extubation failure (EF) in high-risk infants younger than three months after congenital heart surgery (CHS). DESIGN: This was a single-center, randomized, unblinded clinical trial. SETTING: The study was performed in a teaching hospital. PARTICIPANTS: Between January 2020 and January 2021, a total of 150 infants underwent CHS in the authors' hospital. INTERVENTIONS: Infants younger than three months with a high risk for extubation failure who were ready for extubation were randomized to either an NHFOV therapy group or an NIPPV therapy group, and received the corresponding noninvasive mechanical ventilation to prevent EF. MEASUREMENTS: Primary outcomes were reintubation, long-term noninvasive ventilation (NIV) support (more than 72 hours), and the time in NIV therapy. The secondary outcomes were adverse events, including mild-moderate hypercapnia, severe hypercapnia, severe hypoxemia, treatment intolerance, signs of discomfort, unbearable dyspnea, inability to clear secretions, emesis, and aspiration. MAIN RESULTS: Of 92 infants, 45 received NHFOV therapy, and 47 received NIPPV therapy after extubation. There were no significant differences between the NHFOV and the NIPPV therapy groups in the incidences of reintubation, long-term NIV support, and total time under NIV therapy. No significant difference was found of the severe hypercapnia between the two groups, but NHFOV treatment significantly decreased the rate of mild-moderate hypercapnia (p < 0.05). Other outcomes were similar in the two groups. CONCLUSIONS: Among infants younger than three months after CHS who had undergone extubation, NIPPV therapy and NHFOV therapy were the equivalent NIV strategies for preventing extubation failure, and NHFOV therapy was more effective in avoiding mild-moderate hypercapnia.

3.
Sci Rep ; 10(1): 9803, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32555237

RESUMO

Mid-infrared (MIR) light sources have much potential in the study of Dirac-fermions (DFs) in graphene and topological insulators (TIs) because they have a low photon energy. However, the topological surface state transitions (SSTs) in Dirac cones are veiled by the free carrier absorption (FCA) with same spectral line shape that is always seen in static MIR spectra. Therefore, it is difficult to distinguish the SST from the FCA, especially in TIs. Here, we disclose the abnormal MIR spectrum feature of transient reflectivity changes (ΔR/R) for the non-equilibrium states in TIs, and further distinguish FCA and spin-momentum locked SST using time-resolved and linearly polarized ultra-broadband MIR spectroscopy with no environmental perturbation. Although both effects produce similar features in the reflection spectra, they produce completely different variations in the ΔR/R to show their intrinsic ultrafast dynamics.

4.
World J Clin Cases ; 8(10): 1995-2000, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32518792

RESUMO

BACKGROUND: Primary intestinal lymphangiectasia (PIL) is a rare congenital protein-losing enteropathy caused by dysplasia of the small intestinal lymphatics. The cause of the disease is unknown. Through a literature review, we found that PIL and tuberous sclerosis complex (TSC) have some common symptoms and molecular pathways. CASE SUMMARY: Here, we present the case of a patient with a three-year history of primary intestinal lymphangiectasia. The patient most recently visited the hospital with abdominal distension and swelling of the left leg. His mother told us that she was diagnosed with TSC one year previously, which alerted us because the patient had multiple regions of pigmentation. To evaluate the condition of the child and make a definite diagnosis, multiple imaging examinations were performed, as was TSC gene analysis. The results met the diagnostic criteria for TSC. The patient was discharged after symptomatic treatment. Through a review of the literature, it can be seen that changes at the molecular gene level of TSC can lead to abnormal lymphatic vessels. CONCLUSION: In summary, when patients with hypomelanotic macules or enamel hypoplasia are diagnosed with PIL, TSC gene screening may be important for further diagnosis.

5.
Oncotarget ; 7(14): 18651-64, 2016 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-26919107

RESUMO

Acute lymphoblastic leukemia (ALL) is a common hematological malignancy characterized by the uncontrolled proliferation of leukemia cells in children. Discovering and developing effective chemotherapeutic drugs are needed for ALL. In this study, we investigated the anti-leukemic activity of butein and its action mechanisms in ALL. Butein was found to significantly suppress the cellular proliferation of ALL cell lines and primary ALL blasts in a dose-dependent manner. It also induced cell cycle arrest by decreasing the expression of cyclin E and CDK2. We also found that butein promoted nuclear Forkhead Class box O3a (FOXO3a) localization, enhanced the binding of FOXO3a on the p27kip1 gene promoter and then increased the expression of p27kip1. Moreover, we showed that FOXO3a knockdown significantly decreased the proliferation inhibition by butein, whereas overexpression of FOXO3a enhanced the butein-mediated proliferation inhibition. However, overexpression of FOXO3a mutation (C-terminally truncated FOXO3a DNA-binding domain) decreased the proliferation inhibition by butein through decreasing the expression of p27kip1. Our results therefore demonstrate the therapeutic potential of butein for ALL via FOXO3a/p27kip1 pathway.


Assuntos
Chalconas/farmacologia , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Proteína Forkhead Box O3/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Transdução de Sinais/efeitos dos fármacos
6.
Mol Cells ; 37(5): 426-34, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24850148

RESUMO

Peptidylarginine deiminase type 2 (PADI2) deiminates (or citrullinates) arginine residues in protein to citrulline residues in a Ca2+-dependent manner, and is found in lymphocytes and macrophages. Vimentin is an intermediate filament protein and a well-known substrate of PADI2. Citrullinated vimentin is found in ionomycin-induced macrophage apoptosis. Citrullinated vimentin is the target of anti-Sa antibodies, which are specific to rheumatoid arthritis, and play a critical role in the pathogenesis of the disease. To investigate the role of PADI2 in apoptosis, we generated a Jurkat cell line that overexpressed the PADI2 transgene from a tetracycline-inducible promoter, and used a combination of 12-O-tetradecanoylphorbol-13-acetate and ionomycin to activate Jurkat cells. We found that PADI2 overexpression reduced the cell viability of activated Jurkat cells in1a dose- and time-dependent manner. The PADI2-overexpressed and -activated Jurkat cells presented typical manifestations of apoptosis, and exhibited greater levels of citrullinated proteins, including citrullinated vimentin. Vimentin overexpression rescued a portion of the cells from apoptosis. In conclusion, PADI2 overexpression induces apoptosis in activated Jurkat cells. Vimentin is involved in PADI2-induced apoptosis. Moreover, PADI2-overexpressed Jurkat cells secreted greater levels of vimentin after activation, and expressed more vimentin on their cell surfaces when undergoing apoptosis. Through artificially highlighting PADI2 and vimentin, we demonstrated that PADI2 and vimentin participate in the apoptotic mechanisms of activated T lymphocytes. The secretion and surface expression of vimentin are possible ways of autoantigen presentation to the immune system.


Assuntos
Apoptose , Hidrolases/metabolismo , Vimentina/fisiologia , Membrana Celular/metabolismo , Citrulina/metabolismo , Expressão Gênica , Humanos , Células Jurkat , Ativação Linfocitária , Processamento de Proteína Pós-Traducional , Transporte Proteico , Proteína-Arginina Desiminase do Tipo 2 , Desiminases de Arginina em Proteínas
7.
J Med Chem ; 55(20): 8657-70, 2012 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-23009169

RESUMO

Oseltamivir phosphonic acid (tamiphosphor, 3a), its monoethyl ester (3c), guanidino-tamiphosphor (4a), and its monoethyl ester (4c) are potent inhibitors of influenza neuraminidases. They inhibit the replication of influenza viruses, including the oseltamivir-resistant H275Y strain, at low nanomolar to picomolar levels, and significantly protect mice from infection with lethal doses of influenza viruses when orally administered with 1 mg/kg or higher doses. These compounds are stable in simulated gastric fluid, liver microsomes, and human blood and are largely free from binding to plasma proteins. Pharmacokinetic properties of these inhibitors are thoroughly studied in dogs, rats, and mice. The absolute oral bioavailability of these compounds was lower than 12%. No conversion of monoester 4c to phosphonic acid 4a was observed in rats after intravenous administration, but partial conversion of 4c was observed with oral administration. Advanced formulation may be investigated to develop these new anti-influenza agents for better therapeutic use.


Assuntos
Acetamidas/síntese química , Antivirais/síntese química , Cicloexenos/síntese química , Influenzavirus A/efeitos dos fármacos , Influenzavirus B/efeitos dos fármacos , Neuraminidase/antagonistas & inibidores , Acetamidas/farmacocinética , Acetamidas/farmacologia , Administração Oral , Animais , Antivirais/farmacocinética , Antivirais/farmacologia , Disponibilidade Biológica , Proteínas Sanguíneas/metabolismo , Cicloexenos/farmacocinética , Cicloexenos/farmacologia , Efeito Citopatogênico Viral/efeitos dos fármacos , Cães , Farmacorresistência Viral , Estabilidade de Medicamentos , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/enzimologia , Vírus da Influenza A Subtipo H1N1/genética , Virus da Influenza A Subtipo H5N1/efeitos dos fármacos , Virus da Influenza A Subtipo H5N1/enzimologia , Influenzavirus A/enzimologia , Influenzavirus A/genética , Influenzavirus B/enzimologia , Células Madin Darby de Rim Canino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microssomos Hepáticos/metabolismo , Mutação , Infecções por Orthomyxoviridae/tratamento farmacológico , Oseltamivir/farmacologia , Ácidos Fosforosos , Ligação Proteica , Ratos , Relação Estrutura-Atividade
8.
Nan Fang Yi Ke Da Xue Xue Bao ; 31(9): 1626-8, 2011 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-21945784

RESUMO

OBJECTIVE: To establish a modified plasma protamine paracoagulation test. METHODS: Plasma protamine paracoagulation, modified plasma protamine paracoagulation and D-dimer (D-D) tests were performed for the plasma samples collected from 98 cases of disseminated intravascular coagulation (DIC) and 156 normal subjects. The sensitivity and specificity of the 3 tests were analyzed. The plasma samples from 8 cases of suspected myocardial infarction were detected using modified plasma protamine paracoagulation for diagnostic purpose. RESULTS: The sensitivity of plasma protamine paracoagulation, modified plasma protamine paracoagulation and D-D tests was 16.33%, 88.76% and 77.56%, and the specificity was 100%, 88.46% and 97.44%, respectively. Positive results occurred earlier in modified plasma protamine paracoagulation test than in plasma protamine paracoagulation and D-D tests in 5 cases of myocardial infarction. CONCLUSION: The modified plasma protamine paracoagulation test has a higher sensitivity than plasma protamine paracoagulation test and a higher specificity than D-D test, and can be helpful in early diagnosis of thrombosis and fibrinolysis.


Assuntos
Testes de Coagulação Sanguínea/métodos , Protaminas/sangue , Trombose/diagnóstico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Trombose/sangue
9.
Appl Microbiol Biotechnol ; 72(1): 197-205, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16547702

RESUMO

A eukaryotic microalga, Chlorella sp. DT, was transformed with the Bacillus megaterium strain MB1 merA gene, encoding mercuric reductase (MerA), which mediates the reduction of Hg2+ to volatile elemental Hg0. The transformed Chlorella cells were selected first by hygromycin B and then by HgCl2. The existence of merA gene in the genomic DNA of transgenic strains was shown by polymerase chain reaction amplification, while the stable integration of merA into genomic DNA of transgenic strains was confirmed by Southern blot analysis. The ability to remove Hg2+ in merA transgenic strains was higher than that in the wild type. The merA transgenic strains showed higher growth rate and photosynthetic activity than the wild type did in the presence of a toxic concentration of Hg2+. Cultured with Hg2+, the expression level of superoxide dismutase in transgenic strains was lower than that in the wild type, suggesting that the transgenic strains faced a lower level of oxidative stress. All the results indicated that merA gene was successfully integrated into the genome of transgenic strains and functionally expressed to promote the removal of Hg2+.


Assuntos
Bacillus megaterium/enzimologia , Chlorella/metabolismo , Compostos de Mercúrio/metabolismo , Oxirredutases/biossíntese , Biodegradação Ambiental , Southern Blotting , Chlorella/efeitos dos fármacos , Chlorella/genética , Clorofila/análise , Clonagem Molecular , DNA Bacteriano/genética , Expressão Gênica , Compostos de Mercúrio/toxicidade , Organismos Geneticamente Modificados/genética , Organismos Geneticamente Modificados/metabolismo , Oxirredutases/genética , Reação em Cadeia da Polimerase , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Superóxido Dismutase/análise
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