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1.
Onco Targets Ther ; 12: 10263-10273, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819511

RESUMO

Background: Inhibitors of immune checkpoints have shown little effect in clinical trials involving glioma patients. Here, we explored novel targets for use in future treatments. Previous studies showed the sialic acid-binding Ig-like lectin (Siglec) family to have a specific role in immunosuppression. We aimed to study the characteristics and immune function of Siglec family members. Methods: Transcriptome data from 1024 glioma samples and 1551 glioma single cells were used in our study. Clinical and molecular pathology information was also included. Statistical, bioinformatical methods, and single-cell sequencing analysis were applied to investigate the role of Siglec family members. Results: Siglecs-5, -7, -9, and -16 showed a significant correlation with immunosuppression in glioma. They are typically expressed in higher grade, IDH-wildtype, and mesenchymal subtype gliomas. Siglec-5, -7, and -9 had a similar immune function to TIM-3, while Siglec-16 was similar to PD-L1, suppressing tumor immunity via different mechanisms. Joint use of Siglec-inhibitors and immune checkpoint inhibitors could prolong the survival of glioma patients. Conclusion: Siglec-5, -7, -9, and -16 suppressed tumor immunity in different ways. Joint usage of inhibitors may be an effective means to improve the efficacy of glioma immunotherapy.

2.
Cancer Med ; 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31851783

RESUMO

BACKGROUND: Glioblastoma is the most malignant tumor of the central nervous system. Several prediction models have been produced to aid in prognosis assessment. Age, a primary decision factor for prognosis, is associated with increased genomic alterations, however the exact link between increased age and poor prognosis is unknown. OBJECTIVE: In this study, we aimed to reveal the underlying cause of poor prognosis in elderly patients. METHODS: This study included data on 616 primary GBM tumor samples from the CGGA and TCGA databases and 41 nontumor brain tissue samples obtained from GSE53890. Hallmarks and clinicopathological characteristics were evaluated in both tumor and nontumor brain tissues. The association between choice of treatment regimen and age was measured using ANOVA and Student's t test. RESULTS: Age was a robust predictor of poor prognosis in glioma. No age-related hallmarks of cancer were detected, including pathological characteristics or mutations. However, treatment choice was strongly significantly different between old and young patients. Combined chemo-radiation therapy could benefit old and young GBM patients, however, old patients are currently less likely to choose it. CONCLUSION: The vast divergence in prognosis between young and old GBM patients is largely caused by choice of treatment rather than age-related tumor genomic characteristics. Postoperative standard radio- and chemotherapy provide strong benefits to primary glioblastoma patients of all ages.

3.
Drug Des Devel Ther ; 13: 3331-3342, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571834

RESUMO

Purpose: A fixed-dose combination (FDC) tablet of melitracen/flupentixol has been widely used for depression. The purpose of this study was to assess the safety profile and the relative bioavailability of two FDC products containing 10 mg melitracen and 0.5 mg flupentixol from two different manufacturers, in order to acquire adequate pharmacokinetic evidence for registration approval of the test formulation. Methods: The study was designed as a single-dose, randomized, open-label, 2-period crossover study under fasted or fed conditions in healthy Chinese subjects. Twenty-four subjects (16 men and 8 women) were selected for fasted study, and another 24 cases (16 men and 8 women) were in fed study. Each subject was randomized at the beginning to receive either a single dose of the reference FDC or the test FDC tablet during the first period. Following two-week washout period, all subjects received the alternate formulation during the second period. Blood samples were collected up to 144 hrs after administration. Pharmacokinetic parameters, including Cmax, Tmax, AUC0-t, AUC0-∞, t½, CL/F, and Vd/F were acquired based on the time versus concentration profiles. Then, the geometric mean ratios (GMR) and corresponding 90% CIs were calculated for the determination of bioequivalence analysis. Safety assessment included changes in vital signs and laboratory tests, physical examination findings, and incidence or reports of adverse events (AEs). Results: The present study has clearly indicated the test and the reference FDC products are bioequivalent in terms of rate and extent of drug absorption. GMR of Cmax, AUC0-t, and AUC0-∞ for both flupentixol and melitracen between the two formulation FDC products, and corresponding 90% CIs, were all within the range of 80% to 125% under fasted or fed conditions. Both the test and the reference FDC products indicated good tolerance in all volunteers. Chinese Clinical Trials Registry identifier: CTR20171256.

4.
Clin Drug Investig ; 39(10): 953-965, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31338800

RESUMO

BACKGROUND AND OBJECTIVE: This study was performed in healthy Chinese subjects to evaluate the safety and pharmacokinetic/pharmacodynamic characteristics of a novel injection formulation of dexlansoprazole in the context of single and multiple administration, compared with the original lansoprazole injection. METHODS: Helicobacter pylori-negative healthy volunteers were recruited, and 70 participants were enrolled into five dosing groups (seven males and seven females in each group), including 15 mg once daily (qd), 15 mg every 12 h (q12h), 30 mg qd and 30 mg q12h of dexlansoprazole treatment for 5 days, as well as 30 mg q12h of lansoprazole treatment for 5 days. Blood samples were collected at scheduled time spots postdose on day 1 (first dose) and day 5 (last dose). Twenty-four-hour intragastric pH was continuously monitored on day 0 (baseline) and days 1 and 5. Dexlansoprazole and S-lansoprazole in human plasma were determined by validated chiral liquid chromatography with tandem mass spectrometry, and the pharmacokinetic parameters were determined by a non-compartmental method using Phoenix WinNonlin software. Safety assessment included changes in vital signs and laboratory tests, physical examination findings, and incidence or reports of adverse events. RESULTS: The half-life (t½) and clearance (CL) of dexlansoprazole were 1.76-2.06 h and 4.52-5.40 L/h, respectively, while the t½ and CL of S-lansoprazole were 0.87-1.02 h and 34.66-35.98 L/h, respectively. No drug accumulation after repeated administration was noted. Administration of lansoprazole 30 mg resulted in higher area under the concentration-time curve from time zero to the last measurable concentration (AUCt) of dexlansoprazole than that of dexlansoprazole 15 mg (p = 0.026). Zero to 24 h after q12h multiple dosing, median and mean intragastric pH, percentage of time with the intragastric pH above 4.0 [TpH ≥ 4.0(%)] and percentage of time with the intragastric pH above 6.0 [TpH ≥ 6.0(%)] in the dexlansoprazole 15 mg q12h group were 6.07 ± 0.61, 5.70 ± 0.76, 83.58 ± 12.34, and 53.70 ± 17.06, respectively, which was similar to the lansoprazole 30 mg q12h group, i.e. 6.15 ± 0.62, 5.88 ± 0.67, 87.26 ± 12.08 and 57.00 ± 16.35, respectively. A weak positive correlation between dexlansoprazole AUCt and baseline-adjusted TpH ≥ 4.0(%) over 0-24 h was observed, with Pearson correlation coefficients of 0.437 (p = 0.029), while no correlation was observed between AUCt and baseline-adjusted TpH ≥ 6.0(%) over 0-24 h. CONCLUSION: Every 12 h intravenous dosing of dexlansoprazole up to 30 mg for 5 days was safe and well-tolerated in healthy Chinese subjects. Every 12 h dosing of dexlansoprazole 15 mg has a comparable effect of gastric acid inhibition as lansoprazole 30 mg q12h. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT03120273.


Assuntos
Dexlansoprazol/administração & dosagem , Dexlansoprazol/farmacocinética , Lansoprazol/administração & dosagem , Lansoprazol/farmacocinética , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/farmacocinética , Adulto , China/epidemiologia , Cromatografia Líquida/métodos , Relação Dose-Resposta a Droga , Feminino , Voluntários Saudáveis , Humanos , Infusões Intravenosas , Masculino , Espectrometria de Massas em Tandem/métodos , Adulto Jovem
5.
Front Pharmacol ; 10: 774, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354489

RESUMO

Purpose: The aim of this study was to compare the pharmacokinetics and safety between two vinorelbine formulations [a new oil-in-water emulsion formulation (ANX) versus a previously marketed solution formulation (Navelbine)] in Chinese patients with advanced non-small cell lung cancer (NSCLC). Method: This was a single-center, randomized, open-label study. Eligible patients aged 18-70 years who had histologically or cytologically confirmed NSCLC were enrolled. In cycle 1, the patients alternatively received the two formulations (30 mg/m2, given as a 10-min infusion) with a 7-day interval. Samples for pharmacokinetic analysis were taken during cycle 1. For all subsequent 21-day cycles (maximum four cycles), ANX was administered on days 1 and day 8. Bioequivalence analysis was performed on Cmax, AUClast, and AUCinf. The safety profiles and anti-tumor effects were also determined. Results: From March 2013 to January 2015, 24 patients were enrolled and 20 were eligible for pharmacokinetic evaluation. The 20 subjects in the pharmacokinetic analysis set had a median age of 61 years (range, 37-70 years), and 15 patients were male (75%). Mean vinorelbine Cmax values for ANX and Navelbine were 1,317.40 and 1,446.30 ng/mL, respectively. Corresponding AUClast values were 797.08 and 924.26 ng·h/mL, respectively. AUCinf values were 830.14 and 957.16 ng·h/mL, respectively. Treatment ratios of the geometric means were 90.00% (90% CI, 83.22-99.07%) for Cmax, 86.92% (90% CI, 80.91-93.37%) for AUClast, and 87.44% (90% CI, 82.08-93.16%) for AUCinf. These results met the required 80-125% bioequivalence criteria. The most frequently reported adverse events after vinorelbine administration were neutropenia, leucopenia, neutropenic fever, and constipation. Conclusion: At therapeutic dosage levels, pharmacokinetic behavior and safety profiles were similar for both formulations. Chinese National Registry Code: ChiCTR-IPR-15005856.

7.
Huan Jing Ke Xue ; 39(8): 3557-3562, 2018 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-29998661

RESUMO

To study the emission characteristics of volatile organic malodorous compounds and identify the characteristic substances of associated industries, the components of VOCs of typical industries were detected and analyzed in an industrial area of south China. The results showed that there are certain differences in the material composition among different companies, and there are also certain differences in the composition of different processes in the same company. For the automobile manufacturing industry, alcohols and esters were the main substances in the spraying workshop, accounting for 21.87% and 21.62%, respectively, and aromatic hydrocarbons were the typical substances in the drying workshop, accounting for 41.14%. Concerning the electronic components industry, esters were the main substances, accounting for 67.99% in the spraying and coating workshop. Regarding the coating production industry, esters were the main substances in the two paint companies, but the emission ratio of aromatic hydrocarbons was the second highest in one company and the emission ratio of ketone was the second highest in the other company. For the printing industry, alcohols were the characteristic substances, accounting for 99.32%. Concerning the refrigeration industry, alkanes were the most abundant compounds, accounting for 83.01%. Esters (ethyl acetate, butyl acetate, and isobutyl acetate), aromatic hydrocarbons (toluene, ethylbenzene, and styrene), and alcohol ketones (ethanol, methyl isobutyone, and 2-butanone) were preliminarily identified as characteristic malodorous compounds of the industries using organic solvents.

8.
Front Behav Neurosci ; 12: 18, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29497367

RESUMO

This paper uses a newly defined functional connectome and connectome values calculated in time domain of simulated neurotransmitter release (NTR) from an electrocorticogram (ECoG) to distinguish between conditioned and unconditioned stimuli. The NTR derived from multiple channels releasing one quantum at the same time suggests that one functional connectome occurs across those channels at that time. During the first 600 ms after conditional stimulation, the connectome indexes of the 64-channel NTR trains were sorted from the 8 to 20 Hz band obtained from filtered rabbit ECoGs recorded from the visual cortices. In the small scale visual cortex area, this association was significantly larger than the habituation, even though the trial-to-trail variability of large scale synchrony after conditional stimulation is increased, which is also consistent with the hypothesis that attention decreases coherence of lower frequency within each cortical area. The increased conectome index suggests that the stimuli related to association are able to generate stronger substantial responses in the small scale visual cortex than habituation. That is, besides of the background cortical states as well as attention-related decreases in synchrony of lower frequency, the increased part of neurotransmitters released simultaneously from the pre-synaptic terminals of small scale visual cortex for association is larger than habituation.

9.
J Sep Sci ; 41(8): 1781-1790, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29331063

RESUMO

Physalins are the major steroidal constituent of Physalis plants and display a range of biological activities. For this study, a rapid and sensitive high-performance liquid chromatography with triple quadrupole mass spectrometry method was developed for the simultaneous quantification of six physalins. Specifically, it was for the quantification of physalin A, physalin B, physalin D, physalin G, 4,7-didehydroneophysalin B, and isophysalin B in rat plasma and rat intestinal bacteria. After a solid-phase extraction, analytes and internal standards (prednisolone) were separated on a Shield reverse-phase C18 column (measuring 3 mm × 150 mm with an internal diameter of 3.5 µm) and determined using multiple reactions in a monitoring mode with a positive-ion electrospray ionization source. The mobile phase was a mixture of 0.1% formic acid in water (A) and acetonitrile (B) and was used at a flow rate of 0.6 mL/min. The intra- and interday precisions were within 15% with accuracies ranging from 86.2 to 114%. The method was validated and successfully applied to pharmacokinetics and stability studies of six physalins in rat plasma and rat intestinal bacteria, respectively. The results showed that physalin B and isophysalin B could not be absorbed by rats, and rat intestinal bacteria could quickly transform physalins.


Assuntos
Meios de Cultura/química , Intestinos/química , Secoesteroides/farmacocinética , Vitanolídeos/farmacocinética , Animais , Cromatografia Líquida , Feminino , Intestinos/microbiologia , Masculino , Espectrometria de Massas , Conformação Molecular , Ratos , Ratos Sprague-Dawley , Secoesteroides/sangue , Extração em Fase Sólida , Vitanolídeos/sangue
10.
Hum Vaccin Immunother ; 13(9): 2078-2085, 2017 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-28708962

RESUMO

BACKGROUND: To determine the safety and immunogenicity of a novel recombinant adenovirus type 5 vector based Ebola virus disease vaccine (Ad5-EBOV) in Africans in China. METHODS: A phase 1, dose-escalation, open-label trial was conducted. 61 healthy Africans were sequentially enrolled, with 31 participants receiving one shot intramuscular injection and 30 participants receiving a double-shot regimen. Primary and secondary end points related to safety and immunogenicity were assessed within 28 d after vaccination. This study was registered with ClinicalTrials.gov (NCT02401373). RESULTS: Ad5-EBOV is well tolerated and no adverse reaction of grade 3 or above was observed. 53 (86.89%) participants reported at least one adverse reaction within 28 d of vaccination. The most common reaction was fever and the mild pain at injection site, and there were no significant difference between these 2 groups. Ebola glycoprotein-specific antibodies appeared in all 61 participants and antibodies titers peaked after 28 d of vaccination. The geometric mean titres (GMTs) were similar between these 2 groups (1919.01 vs 1684.70 P = 0.5562). The glycoprotein-specific T-cell responses rapidly peaked after 14 d of vaccination and then decreased, however, the percentage of subjects with responses were much higher in the high-dose group (60.00% vs 9.68%, P = 0.0014). Pre-existing Ad5 neutralizing antibodies could significantly dampen the specific humoral immune response and cellular response to the vaccine. CONCLUSION: The application of Ad5-EBOV demonstrated safe in Africans in China and a specific GP antibody and T-cell response could occur 14 d after the first immunization. This acceptable safety profile provides a reliable basis to proceed with trials in Africa.


Assuntos
Anticorpos Antivirais/sangue , Vacinas contra Ebola/efeitos adversos , Vacinas contra Ebola/imunologia , Ebolavirus/imunologia , Doença pelo Vírus Ebola/prevenção & controle , Imunogenicidade da Vacina , Adulto , África/epidemiologia , Anticorpos Neutralizantes/sangue , China , Vacinas contra Ebola/administração & dosagem , Feminino , Febre/etnologia , Voluntários Saudáveis , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/etnologia , Doença pelo Vírus Ebola/imunologia , Humanos , Imunidade Celular , Imunidade Humoral , Injeções Intramusculares , Masculino , Glicoproteínas de Membrana/imunologia , Pessoa de Meia-Idade , Linfócitos T/imunologia , Vacinação , Adulto Jovem
11.
J Sep Sci ; 40(11): 2355-2365, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28388002

RESUMO

Physalin D is known to show extensive bioactivities. However, no excretion study has elucidated the excretion of physalin D and its metabolites. This study investigates the excretion of physalin D and its metabolites in rats. Metabolites in rat urine and feces were separated and identified by liquid chromatography with triple quadrupole time-of-flight mass spectrometry. Furthermore, a validated high-performance liquid chromatography with tandem mass spectrometry method was developed to quantify physalin D, physalin D glucuronide, and physalin D sulfate in rat feces and urine after the intragastric administration of physalin D. The analyte showed good linearity over a wide concentration range (r > 0.995), and the lower limit of quantification was 0.0532 µg/mL and 0.226 µg/g for urine and feces, respectively. Nine metabolites, including five phase I and four phase II metabolites, were identified and clarified after dosing in vivo. Only 4.0% of the gavaged dose, including physalin D and its phase II metabolites, was excreted in urine, whereas 10.8% was found in feces in the unchanged form. The results indicate that the extensive and rapid metabolism may be the main factors leading to the short half-life of physalin D. These results can provide a basis for further studies on the structural modification and pharmacology of physalin D.


Assuntos
Fezes/química , Secoesteroides/farmacocinética , Secoesteroides/urina , Animais , Cromatografia Líquida de Alta Pressão , Ratos , Espectrometria de Massas em Tandem
12.
Science ; 355(6325): 616-619, 2017 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-28183975

RESUMO

Dual-functioning displays, which can simultaneously transmit and receive information and energy through visible light, would enable enhanced user interfaces and device-to-device interactivity. We demonstrate that double heterojunctions designed into colloidal semiconductor nanorods allow both efficient photocurrent generation through a photovoltaic response and electroluminescence within a single device. These dual-functioning, all-solution-processed double-heterojunction nanorod light-responsive light-emitting diodes open feasible routes to a variety of advanced applications, from touchless interactive screens to energy harvesting and scavenging displays and massively parallel display-to-display data communication.

13.
Infect Genet Evol ; 45: 250-255, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27590713

RESUMO

Banna virus (BAV) is an emerging pathogen that causes human viral encephalitis and has been isolated from types of blood-sucking insects and mammals in Asia. However, there are no reported systematic studies that describe the origin and evolution of BAV. Here, a phylogenetic analysis of BAVs isolated from a variety of potential vectors and vertebrate hosts worldwide revealed that BAVs emerged in the beginning of the 20th century and do not exhibit a species barrier. The mean substitution rate of BAVs was 2.467×10-2substitution/site/year (95% HPD, 1.093×10-3 to 5.628×10-2). The lineage is mainly composed of BAVs from high-latitude regions, which are the most recently emerged viruses with significantly higher substitution rates compared with the lineage comprised of the isolates from middle or low-latitude regions. The genetic differences between BAV strains are positively correlated with the geographic distribution. Strains from the same latitude regions are almost 100% identical, whereas the differences between strains from long distance regions with different latitudes could be >60%. Our results demonstrate that BAV is an emerging virus at a stage that involves rapid evolution and has great potential for introduction into non-endemic areas. Thus, enhanced surveillance of BAV is highly recommended worldwide.


Assuntos
Coltivirus/classificação , Coltivirus/genética , Doenças Transmissíveis Emergentes/virologia , Encefalite por Arbovirus/virologia , Animais , Evolução Molecular , Humanos , Filogenia , RNA Viral/análise , RNA Viral/genética
14.
Int J Dermatol ; 55(7): 791-800, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26967585

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a chronic or relapsing inflammatory disorder of the skin that frequently precedes asthma and allergic disorders. This study aimed to identify candidate genes related to AD using bioinformatic methods. METHODS: The microarray data of GSE32924, including 12 nonlesional AD (ANL) and 13 lesional AD (AL) skin samples obtained from 14 patients with AD as well as eight other normal human skin samples, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened in ANL and AL skin samples compared with normal controls, followed by gene ontology (GO) and pathway enrichment analyses. Furthermore, the selected overlapping DEGs were analyzed to identify co-expressed genes, and a co-expression network was established. GeneCodis database was selected for functional annotation of the differentially co-expressed genes and a regulatory network was constructed. RESULTS: Compared with normal controls, 438 DEGs were identified in ANL skin samples and were mainly enriched in two pathways and the GO terms associated with epidermis development. Besides, 779 DEGs were identified in AL skin samples and were mainly enriched in four pathways and GO terms associated with immune response. Stimulated by retinoic acid 13 (STRA13), presenilin enhancer gamma secretase subunit (PSENEN), and nucleosome assembly protein 1-like 2 (NAP1L2) were significantly enriched by integration analysis of the co-expression and regulatory network. CONCLUSION: Genes STRA13, PSENEN, and NAP1L2 were presumed to play critical roles in AD and they may serve as potential targets for the treatment of AD.


Assuntos
Secretases da Proteína Precursora do Amiloide/genética , Biologia Computacional , Proteínas de Ligação a DNA/genética , Dermatite Atópica/genética , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Estudos de Casos e Controles , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Pele
15.
Int J Clin Pharmacol Ther ; 54(2): 115-24, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26636422

RESUMO

OBJECTIVE: Febuxostat is a novel non-purine selective inhibitor of xanthine oxidase indicated for the chronic management of hyperuricemia in patients with gout. The aim of the present study was to evaluate the pharmacokinetic properties and tolerability of single and multiple oral administrations of febuxostat capsules in healthy Chinese volunteers. METHODS: This openlabel, single- and multiple-dose three-way crossover study was conducted in healthy Chinese volunteers. Subjects were randomized to receive a single dose of febuxostat 40, 80, or 120 mg in separate trial periods, with a 1-week washout between periods. Those allocated to the 40 mg and 80 mg dose continued into the multiple-dose phase, in which they received 40 mg or 80 mg once daily for 6 consecutive days. During the course of the study, blood samples were collected and the concentrations of febuxostat were determined using LC-MS/MS. Pharmacokinetic parameters were estimated using a noncompartmental model. Tolerability was determined using clinical evaluation and monitoring of adverse events (AEs). RESULTS: 12 healthy Chinese volunteers were enrolled and completed 3 treatment periods. After oral administration of single doses of 40, 80, and 120 mg of febuxostat, the mean (SD) Cmax was 2,835.43 (1,136.41), 5,356.75 (1,711.33), and 7,718.21 (2,446.34) ng/mL, respectively; the AUC0-48h was 8,821.10 (3,018.35), 17,854.46 (5,113.28), and 30,832.05 (10,992.20) ng×h/ mL; the AUC0-∞ was 8,990.33 (3,046.14), 18,193.58 (5,160.80), and 31,466.93 (1,1074.74) ng×h/mL; the t1/2 was 5.95 (2.71), 9.41 (7.47), and 12.34 (10.34) hours; the Cl/F was 4.81 (1.18), 4.70 (1.21), and 4.18(1.19) L/h; and the Vz/F was 39.66 (16.69), 62.72 (51.41), and 73.41 (64.84) L. After administration of multiple doses of 40 and 80 mg febuxostat, the mean (SD) Cmax,ss was 2,762.38 (1,331.96) and 5,047.27 (1,456.57) ng/mL; the Cmin,ss was 124.10 (6.32) and 46.93 (15.86) ng/mL; the AUCss,0-τ was 8,525.49 (2,160.64) and 16,757.12 (4,223.17) ng×h /mL; the steadystate plasma concentration (Css) was 355.23 (90.03) and 698.21 (175.97) ng/mL; the t1/2 was 7.68 (3.30) and 11.33 (6.94) hours; the Cl/F was 4.99 (1.30) and 5.05 (1.22) L/h; and the Vz/F was 54.10 (24.10) and 85.51 (65.99) L. No serious AEs were reported, and there were no discontinuations due to AEs. CONCLUSION: The PK of febuxostat exhibited dose proportional kinetics from 40 to 120 mg dose. After multiple doses, the pharmacokinetic parameters of febuxostat were consistent with those after single doses. There was no accumulation in febuxostat exposure in healthy Chinese between multiple doses and single dose. At the doses studied, febuxostat appeared to be well tolerated in these healthy volunteers.


Assuntos
Febuxostat/farmacocinética , Administração Oral , Adolescente , Adulto , Estudos Cross-Over , Febuxostat/administração & dosagem , Febuxostat/efeitos adversos , Feminino , Humanos , Masculino
16.
Chemphyschem ; 17(5): 741-51, 2016 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-26525301

RESUMO

Cu2 S/ZnS heterostructured nanorods (HNRs) with uncommon morphologies are achieved through single-pot and multi-batch synthetic strategies. In both cases, Cu2 S NRs form first, which then undergo partial cation exchange and solution-liquid-solid (SLS)-like growth catalyzed by the remaining Cu2 S parts of the NRs. The location and the volume of ZnS achieved through partial cation exchange control the size of the Cu2 S catalysts, which in turn determine whether tapered rod-rod, body/tail, or barbell-like structure results from subsequent SLS-like growth. Concurrent cation exchange can sometimes cause Cu2 S catalysts to be lost during SLS-like growth, leading to further diversity in achievable morphologies of Cu2 S/ZnS HNRs. Additional insights are gained on how parameters such as Zn precursor, ligand choice, and concentration alter cation exchange and SLS-like growth steps.

17.
Drug Des Devel Ther ; 9: 5687-95, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26527863

RESUMO

BACKGROUND: Dicloxacillin, a semisynthetic isoxazolyl penicillin antibiotic, has antimicrobial activity against a wide variety of gram-positive bacteria including Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumonia, Streptococcus epidermidis, Streptococcus viridans, Streptococcus agalactiae, and Neisseria meningitidis. The objective of this study was to evaluate the safety and pharmacokinetic profile of dicloxacillin after single and multiple oral dose in healthy Chinese volunteers. METHODS: A single-center, open-label, randomized, two-phase study was conducted in 16 subjects. In the single-dose phase, subjects were randomly assigned to receive single doses of 0.25, 0.5, 1.0, and 2.0 g of dicloxacillin sodium capsule in a 4-way crossover design with a 5-day washout period between administrations. In the multiple-dose phase, subjects were assigned to receive 0.25 or 0.5 g every 6 hours for 3 days in a 2-way crossover design. Plasma and urine pharmacokinetic samples were assayed by a validated high-performance liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were calculated and analyzed statistically. Safety assessments were conducted throughout the study. RESULTS: Following a single oral dose of 0.25-2.0 g dicloxacillin sodium, the maximum plasma drug concentration (Cmax) and the corresponding values for the area under the concentration- time curve from 0 to 10 hours (AUC0-10 h) increased in a dose-proportional manner. The mean elimination half-life (t1/2) was in the range of 1.38-1.71 hours. Dicloxacillin was excreted in its unchanged form via the kidney, with no tendency of accumulation, and varied from 38.65% to 50.10%. No appreciable accumulation of drug occurred with multiple oral doses of dicloxacillin. No serious adverse events were reported. Adverse events were generally mild. CONCLUSION: Dicloxacillin was safe and well tolerated in the volunteers and displayed linear increases in the Cmax and AUC0-10 h values.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Dicloxacilina/administração & dosagem , Dicloxacilina/farmacocinética , Administração Oral , Adolescente , Adulto , Antibacterianos/efeitos adversos , Antibacterianos/sangue , Antibacterianos/urina , Área Sob a Curva , Grupo com Ancestrais do Continente Asiático , China , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Dicloxacilina/efeitos adversos , Dicloxacilina/sangue , Dicloxacilina/urina , Esquema de Medicação , Feminino , Meia-Vida , Voluntários Saudáveis , Humanos , Modelos Lineares , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Modelos Biológicos , Eliminação Renal , Espectrometria de Massas em Tandem , Adulto Jovem
18.
Nanoscale Res Lett ; 10(1): 423, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26510444

RESUMO

Annealing or growth at high temperatures for an extended period of time is considered detrimental for most synthetic strategies for high-quality Mn-doped II-VI semiconductor nanocrystals. It can lead to the broadening of size distribution and, more importantly, to the loss of dopants. Here, we examine how ripening can be beneficial to doping in a simple "heat-up" approach, where high dopant concentrations can be achieved. We discuss the interplay of the loss of dopants, Ostwald ripening, and the clustering of Mn near the surface during nanocrystal growth. Smaller nanocrystals in a reaction batch, on average, exhibit higher undesirable band-edge photoluminescence (PL) and lower desirable dopant PL. The optimization of dopant loss and the removal of such smaller undesirable nanocrystals through Ostwald ripening along with surface exchange/passivation to remove Mn clustering lead to high Mn PL quantum yields (45 to 55 %) for ZnSxSe1-x, ZnS, CdS, and CdSxSe1-x host nanocrystals. These results provide an improved understanding of the doping process in a simple and potentially scalable synthetic strategy for achieving "pure" and bright dopant emission.

19.
Artigo em Inglês | MEDLINE | ID: mdl-26117310

RESUMO

Camellianin A is a major active constituent of Adinandra nitida. A LC-MS/MS method for the determination of camellianin A and its metabolite (camellianin B) in rat plasma and tissues was developed and applied to a pharmacokinetics and tissue distribution study. Samples were separated on a Waters HSS T3 column with a mobile phase consisted of methanol and water (containing 0.1% formic acid). MS/MS detection was carried out on a triple-quadruple mass spectrometer under negative ESI mode. Pharmacokinetics study showed that camellianin A was rapidly eliminated with a t1/2 of 92.6±41.4h and CL of 3.19±0.471L/min/kg. Additionally, camellianin A showed a low oral bioavailability of 2.99% and a narrow tissue distribution; however, camellianin B was proved to have a wide tissue distribution with brain penetration. The data presented in this study provides useful information for the further applications of A. nitida and camellianin A.


Assuntos
Cromatografia Líquida/métodos , Flavonoides/farmacocinética , Espectrometria de Massas em Tandem/métodos , Animais , Flavonoides/sangue , Flavonoides/química , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
20.
World J Surg Oncol ; 13: 122, 2015 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-25889889

RESUMO

BACKGROUND: The prognostic role of inflammation indices, such as the neutrophil-to-lymphocyte ratio (NLR) in gastric cancer (GC) remains controversial. We conducted a meta-analysis to determine the predictable value of NLR in the clinical outcome of GC patients. METHODS: We searched Embase, PubMed and the Cochrane Library database for relevant randomised controlled trials. Statistical analyses were conducted to calculate the hazard ratio (HR) and 95% confidence intervals of overall survival (OS) and progression-free survival (PFS) using either random-effect or fixed-effect models according to the heterogeneity of the included studies. An analysis was carried out based on data from nine studies to evaluate the association between NLR and OS in patients with GC. RESULTS: Our analysis indicated that elevated pre-treatment NLR predicted poorer OS (HR: 2.16, 95% CI: 1.86 to 2.51, P < 0.001) and PFS (HR 2.78, 95% CI: 1.95 to 3.96; P < 0.00001) in patients with GC. Over a 3-year follow-up period, high NLR was a significant predictor of poor outcomes at year 1 (HR 1.99; 95% CI: 1.39 to 2.85; P = 0.0002), year 2 (HR 2.24; 95% CI: 1.69 to 2.97; P < 0.00001) and year 3 (HR 2.80; 95% CI: 1.98 to 3.96; P < 0.00001). CONCLUSIONS: Elevated preoperative NLR is associated with poorer rates of survival in GC patients and may play a role in GC surveillance programmes as a means of delivering more personalised cancer care.


Assuntos
Linfócitos/patologia , Neutrófilos/patologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Humanos , Prognóstico , Taxa de Sobrevida
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