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1.
Drug Test Anal ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32043805

RESUMO

Lumiracoxib is a selective cyclooxygenase-2 inhibitor, which has been reported to cause rare but severe liver injury. Considering that lumiracoxib has a carboxylic group in the molecule, glucuronidation to form acylglucuronide would be one of the possible mechanisms of lumiracoxib-induced liver injury. The aim of this study was to identify the metabolites of lumiracoxib that were formed via acyl-glucuronidation in human liver microsomes using glutathione (GSH) and N-acetyl-lysine (NAL) as trapping agents by liquid chromatography combined with high resolution mass spectrometry. The structures of the detected metabolites were identified by their accurate masses, fragment ions, and retention times. Under the current conditions, eight lumiracoxib associated metabolites were identified. With the presence of UDPGA, lumiracoxib was biotransformed into lumiracoxib-1-O-acylglucuronide (M1) and 4'-hydroxyl-lumiracoxib-1-O-acylglucuronide (M2), both of which were reactive and prone to react with GSH to form drug-S-acyl-GSH adducts (M3 and M4) through transacylation. In addition to reaction with GSH, the formed 1-O-acylglucuronides were chemically unstable (T1/2 = 1.5 h in phosphate buffer) and rearranged to 2-, 3-, and/or 4-isomers, which further underwent ring-opening to form aldehyde derivatives and then reacted with NAL to yield Schiff base derivatives (M5-M8). The present study provides a clear bioactivation profile of lumiracoxib through acyl glucuronidation, which would be one of the mechanisms attributed to liver injury caused by lumiracoxib.

2.
Int J Biol Macromol ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31756487

RESUMO

OBJECTIVE: Fas is a positive regulator of Th17 cells differentiation in experimental autoimmune encephalomyelitis (EAE). However, its upstream regulators are still not fully determined. This study was designed to explore the upstream regulators of Fas in regulating Th17 cells differentiation in EAE. METHODS: The mouse model of EAE was established by myelin oligodendrocyte glycoprotein injection. Th17 cells differentiation was induced by IL-23, IL-6 and TGF-ß. RESULTS: Down-regulated Hsp70 and miR-374c and up-regulated Fas were observed in the spleen and brain of EAE mice. Hsp70 overexpression evidently reduced Fas protein level, but not mRNA level. The luciferase reporter assay indicated that miR-374c targets Fas. Overexpression of miR-374c down-regulated the mRNA and protein level of Fas. The concentration of IL-17A in CD4+ T-cells was reduced by miR-374c or Hsp70 overexpression, and Fas overexpression altered this trend. Hsp70 did not regulate the expression of miR-374c, and likewise, miR-374c did not regulate the expression of Hsp70. Further results suggested that Hsp70 and miR-374c regulated Fas expression through different ways to affect Th17 cells differentiation in EAE. CONCLUSIONS: This study suggested that down-regulated miR-374c and Hsp70 promote Th17 cell differentiation by inducing Fas expression in EAE.

3.
Medicine (Baltimore) ; 97(50): e13625, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30558047

RESUMO

RATIONALE: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an auto-immune and paraneoplastic encephalitis with prominent neuropsychiatric manifestations. The N-methyl-D-aspartate receptor is located in the forebrain and hippocampus and plays a role in learning and memory. PATIENT CONCERNS: A 29-year-old female patient with anti-NMDAR encephalitis, was reported and we also reviewed the literature and summarised the characteristics of the cases. DIAGNOSES: In the present study, we reported 1 patient with anti-NMDAR encephalitis diagnosed by the detection of anti-NMDAR antibodies in serum and cerebrospinal fluid (CSF). INTERVENTIONS: The patient received glucocorticoids and anti-epilepsy treatment as well as human immunoglobulin treatment. OUTCOMES: After treatment, the patient gradually regained consciousness and was discharged after 3 months of rehabilitation. At the follow-up 2 months later, the patient had the sequelae of memory impairment and limb movement disorders. LESSONS: An accurate early diagnosis and active treatment are crucial to the improvement in the prognosis of patients with anti-NMDAR receptor encephalitis.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Anticonvulsivantes/administração & dosagem , Glucocorticoides/administração & dosagem , Imunoglobulinas/administração & dosagem , Receptores de N-Metil-D-Aspartato/imunologia , Adulto , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Encefalite Antirreceptor de N-Metil-D-Aspartato/fisiopatologia , Encefalite Antirreceptor de N-Metil-D-Aspartato/psicologia , Anticorpos/sangue , Anticorpos/líquido cefalorraquidiano , Diagnóstico Precoce , Feminino , Humanos , Imunomodulação , Transtornos da Memória/etiologia , Transtornos dos Movimentos/etiologia , Prognóstico , Resultado do Tratamento
4.
Neurology ; 90(17): e1523-e1529, 2018 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-29572284

RESUMO

OBJECTIVE: To investigate the efficacy and safety of IV aminophylline for patients with postdural puncture headache (PDPH). METHODS: We randomly assigned patients to groups receiving either 250 mg IV aminophylline or a placebo within 3 hours of symptom onset once daily for 2 consecutive days. The primary endpoint was headache severity 8 hours after treatment. We assessed this using visual analog scale (VAS) scores taken from patients in a standing position. We also recorded posttreatment VAS score changes, Patient Global Impression of Change (PGIC) scores, and adverse events. We performed an intention-to-treat analysis. RESULTS: We enrolled 126 patients with PDPH at 5 centers in China (62 assigned to the aminophylline group and 64 to the placebo group). The median age was 37 years, and 96 (76.2%) patients were women. Compared to the placebo-treated patients, the aminophylline-treated patients had significantly lower mean VAS scores 8 hours after treatment (5.34 vs 2.98, p < 0.001) and were significantly more likely to report improvements on the PGIC (39.1% vs 72.6%, p < 0.01). This therapeutic effect was already evident at the 30-minute time point and persisted for 2 days. There was no significant difference in the incidence of adverse events (4.8% vs 1.6%, p = 0.589). CONCLUSIONS: IV aminophylline is an effective and safe early-stage treatment for patients with PDPH. CLINICALTRIALSGOV IDENTIFIER: NCT02522013. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for people with PDPH, IV aminophylline reduces headache severity.


Assuntos
Aminofilina/uso terapêutico , Inibidores de Fosfodiesterase/uso terapêutico , Cefaleia Pós-Punção Dural/tratamento farmacológico , Administração Intravenosa , Adolescente , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Resultado do Tratamento , Escala Visual Analógica , Adulto Jovem
5.
Medicine (Baltimore) ; 96(42): e6933, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29049166

RESUMO

RATIONALE: Urinary lithiasis is one of severe postoperative complications in patients undergoing renal transplantation, possibly leading to anuria, urinary infection, or even acute renal failure. Potassium sodium hydrogen citrate (PSHC), a potassium-bearing citrate, is commonly prescribed to prevent stone formation. PATIENT CONCERNS: A 25-year-old man (patient 1) and a 31-year-old man (patient 2) receiving renal transplantation for end-stage renal disease (ESRD) were enrolled in this study. They were given 10 g/day of PSHC granules from the ninth day to the 17th day after surgery. Patient 1 presented chest tightness, nausea, muscle weakness, and ascending paralysis on the 10th day. Patient 2 presented weak waves on EGG on the 17th day. Moreover, their serum potassium concentrations (SPCs) were 7.67 and 6.05 mmol/L, respectively. DIAGNOSIS: Acute hyperkalemia. INTERVENTIONS: Hemo-filtration was performed for patient 1, while patient 2 received 10% calcium gluconate 10 mL, 5% NaHCO3 125 mL, and 10% glucose 500 mL with the addition of 10 units of insulin through intravenous drip. OUTCOMES: Their SPCs dropped to the normal range. LESSONS: Physicians should pay close attentions to potential risks caused by PSHC, and monitor the SPCs to minimize the occurrence of hyperkalemia.


Assuntos
Diuréticos/efeitos adversos , Hiperpotassemia/induzido quimicamente , Complicações Pós-Operatórias/prevenção & controle , Citrato de Potássio/efeitos adversos , Urolitíase/prevenção & controle , Adulto , Diuréticos/administração & dosagem , Humanos , Transplante de Rim/efeitos adversos , Masculino , Complicações Pós-Operatórias/etiologia , Citrato de Potássio/administração & dosagem , Urolitíase/etiologia
6.
Inorg Chem ; 56(16): 10007-10012, 2017 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-28771000

RESUMO

By application of a newly designed T-shaped ligand 5-(4-pyridin-4-yl-benzoylamino)isophthalic acid (H2PBAI) to assemble with Zn(II) ions under solvothermal conditions, a novel porous polyhedral metal-organic framework (Zn-PBAI) with pcu topology has been obtained. When treated as a precursor by annealing of Zn-PBAI at various temperatures, porous carbon polyhedra (PCP) were prepared and tested as an anode material for lithium-ion batteries. The results show that PCP carbonized at 1000 °C (PCP-1000) manifest the highest reversible specific capacity of about 1125 mAh g-1 at a current of 500 mA g-1 after 200 cycles, which is supposed to benefit from the large accessible specific area and high electric conductivity. Moreover, PCP-1000 electrode materials also exhibit superior cyclic stability and good rate capacity.

7.
J Tradit Chin Med ; 36(5): 649-53, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-29933534

RESUMO

OBJECTIVE: To analyze the distribution and combined regulation of elements of symptom patterns in the diagnosis of insomnia with Traditional Chinese Medicine (TCM). METHODS: The samples were collected from the patients, diagnosed with insomnia, of Henan Province Hospital of TCM between June 2011 and September 2013. The symptom patterns in insomnia were extracted. Next, symptom differentiation, characteristics of polysomnography (PSG), distribution and combined regulation of these symptom patterns were conducted by tests. RESULTS: In total, 286 eligible patients were recruited. The main locations of the disease symptom elements were the brain and heart, and the main characteristics of the disease symptom elements were phlegm-heat, Yin-deficiency and Qi-stagnation. The elements from two or three symptom patterns were commonly manifested in patients with insomnia, especially from three symptom patterns. We also found that all TCM symptom patterns had an effect on polysomnographic indicators in PSG tests. CONCLUSION: The elements of symptom patterns in insomnia were identified as mainly fire-heat and phlegm-heat. The most common patterns of excess were pathogenic fire derived from stagnation of liver- Qi, and mental disturbance due to phlegm-heat, while the most common patterns of deficiency in both the heart and the spleen. There are many differences in PSG indicators of different syndrome patterns of insomnia.


Assuntos
Distúrbios do Início e da Manutenção do Sono/diagnóstico , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Deficiência da Energia Yin/diagnóstico , Deficiência da Energia Yin/fisiopatologia , Adulto Jovem
8.
J Proteomics ; 126: 46-53, 2015 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-26045010

RESUMO

The association of gender with the treatment outcome during long-term antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected patients has been controversial. Here, we performed a comparative proteomic analysis of peripheral blood mononuclear cells (PBMC) by using a label-free shotgun method with nano-LC-MS/MS to investigate the gender differences in responses to long-term ART. This analysis enrolled 30 HIV-infected patients (16 males and 14 females), as well as 20 healthy adults (10 males and 10 females) as control. Quantitative real-time RT-PCR and immunoblotting were used to validate the results of proteomic approach. A total of 53 proteins showing differential expression (± 1.5 fold, p < 0.05) were identified in HIV-infected patients versus healthy adults. Of these proteins, 22 proteins showed identical regulation patterns in both men and women, while 31 proteins were gender-specific (21 men-specific and 10 women-specific proteins). Bioinformatics analysis indicated that long-term ART causes up-regulation of apoptosis, oxidative phosphorylation and mitochondrial dysfunction while down-regulation of oxidative stress and immune system process in men compared to women. These findings point to a concept that gender has a significant influence on the outcomes of ART at protein level and women present a potential favorable immunological pattern and recovery during long-term ART.


Assuntos
Antirretrovirais/administração & dosagem , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , HIV-1 , Leucócitos Mononucleares/metabolismo , Proteoma/biossíntese , Caracteres Sexuais , Adulto , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Infecções por HIV/patologia , Humanos , Leucócitos Mononucleares/patologia , Masculino , Pessoa de Meia-Idade , Proteômica
9.
J Neurochem ; 134(3): 551-65, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25952107

RESUMO

Hypoxia-mediated neurotoxicity contributes to various neurodegenerative disorders, including Alzheimer's disease and multiple sclerosis. Tetramethylpyrazine (TMP), a major bioactive component purified from Ligusticum wallichii Franchat, exhibited potent neuroprotective effect. However, the mechanism of TMP-exerted neuroprotective effect against hypoxia was not clear. In the study, we investigated the mechanism of the neuroprotective effect of TMP against hypoxia induced by CoCl2 in vitro and in vivo. The results showed that TMP could protect against CoCl2 -induced neurotoxicity in PC12 cells and in rats, as evidenced by enhancement of cell viability in PC12 cells and improvement of learning and memory ability in rats treated with CoCl2 . TMP could inhibit mitochondrial dysfunction, mitochondrial apoptotic molecular events, and thus apoptosis induced by CoCl2 . TMP inhibited CoCl2 -increased reactive oxygen species (ROS) level, which may contribute to hypoxia-related neurotoxicity induced by CoCl2 . The antioxidant and neuroprotective activities of TMP involved two pathways: one was the enhancement of nuclear factor erythroid 2-related factor 2 (Nrf2)/catalytic subunit of γ-glutamylcysteine ligase-mediated regulation of GSH and the other was the inhibition of hypoxia-inducible factor 1 α/NADPH oxidase 2 (NOX2)-mediated ROS generation. These two pathways contributed to improvement of oxidative stress and thus the amelioration of apoptosis under hypoxic conditions. These results have appointed a new path toward the understanding of pathogenesis and TMP-related therapy of hypoxia-related neurodegenerative diseases. We proposed two cascades for tetramethylpyrazine-exhibited protective effects against CoCl2 -induced neurotoxicity: One is enhancement of nuclear factor erythroid 2-related factor 2-catalytic subunit of γ-glutamylcysteine ligase-mediated regulation of glutathone and the other was the inhibition of hypoxia-inducible factor 1 α-NADPH oxidase-2-mediated ROS generation. We think these findings should provide a new understanding of pathogenesis and tetramethylpyrazine-related therapy of hypoxia-related neurodegenerative diseases.


Assuntos
Hipóxia Celular/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Pirazinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Imunoprecipitação da Cromatina , Cobalto/toxicidade , Glutamato-Cisteína Ligase/metabolismo , Glutationa/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Glicoproteínas de Membrana/metabolismo , NADPH Oxidase 2 , NADPH Oxidases/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Células PC12 , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Transfecção
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