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1.
Br J Clin Pharmacol ; 88(5): 2396-2407, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34907578

RESUMO

AIMS: Ropeginterferon alfa-2b is a novel, long-acting pegylated interferon alfa-2b. We aimed to evaluate its safety, pharmacokinetics (PK) and pharmacodynamics (PD). METHODS: Thirty-six subjects received single subcutaneous injection of ropeginterferon alfa-2b at doses ranging from 24 to 270 µg, and 12 subjects received pegylated IFN alfa-2a subcutaneously at 180 µg. Primary endpoints were safety/PK profiles of ropeginterferon alfa-2b, while secondary endpoints were to compare PK/PD parameters with pegylated IFN alfa-2a. RESULTS: Adverse events in ropeginterferon alfa-2b and pegylated IFN alfa-2a groups were similar, and most of them were mild or moderate. Mean Cmax increased from 1.78 to 24.84 ng/mL along with the dose escalations in ropeginterferon alfa-2b groups and was 12.95 ng/mL for pegylated IFN alfa-2a. At 180 µg, ropeginterferon alfa-2b showed statistically significant Cmax geometric mean ratio (1.76; P = .0275). Mean Tmax ranged from 74.52 to 115.69 h for ropeginterferon alfa-2b groups, and was 84.25 h for pegylated IFN alfa-2a. Mean AUC0-t increased from 372.3 to 6258 ng•h/mL with the dose escalations in the ropeginterferon alfa-2b groups, while for pegylated IFN alfa-2a it was found to be 2706 ng•h/mL in pegylated IFN alfa-2a. For neopterin and 2',5'-oligoadenylate synthase, mean Emax , Tmax and AUC0-t of ropeginterferon alfa-2b were similar to those of pegylated IFNα-2a at 180 µg. CONCLUSION: Ropeginterferon alfa-2b up to 270 µg was safe and well tolerated. The PK/PD parameters of ropeginterferon alfa-2b showed increase in dose-response. Ropeginterferon alfa-2b had higher drug exposures and showed similar safety profile when compared to pegylated IFN alfa-2a at the same dose level.


Assuntos
Antivirais , Interferon-alfa , Antivirais/efeitos adversos , Humanos , Interferon alfa-2/efeitos adversos , Interferon-alfa/efeitos adversos , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes/efeitos adversos
2.
Adv Ther ; 38(9): 4756-4770, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34328630

RESUMO

INTRODUCTION: Ropeginterferon alfa-2b is a novel mono-pegylated human recombinant interferon (IFN) with the addition of N-terminal proline covalently attached by a 40-kDa polyethylene (peg) moiety. The present study aimed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD) profiles and safety of the product in healthy Chinese. METHODS: Forty subjects were enrolled and treated with a single subcutaneous injection of either 180 mcg peg-IFN alfa-2a or 90, 180, and 270 mcg ropeginterferon alfa-2b. RESULTS: The mean Tmax of ropeginterferon alfa-2b was 92-141 h and the elimination half-life was 78-129 h. Dose-related, non-proportional increase in ropeginterferon alfa-2b exposure was observed, which was higher than for peg-IFN alfa-2a. The PD parameters were similar between each dose level of ropeginterferon alfa-2b. The mean Tmax of ß2-microglobulin ranged from 118 to 132 h after a single dose of ropeginterferon alfa-2b. The average Emax was 3 mcg/ml in all dose levels and the mean AUEC0-t ranged from 1608 to 1775 h/mcg/ml. The TEAEs were comparable among each treatment group and no death nor drug-related SAE was reported. CONCLUSION: Ropeginterferon alfa-2b is safe and well tolerated after a single subcutaneous injection up to 270 mcg in healthy Chinese. CLINICAL TRIAL REGISTRATION: www.chinadrugtrials.org.cn , CTR20190451.


Assuntos
Antivirais , Polietilenoglicóis , Antivirais/uso terapêutico , China , Voluntários Saudáveis , Humanos , Injeções Subcutâneas , Proteínas Recombinantes
3.
Food Chem ; 175: 189-96, 2015 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-25577069

RESUMO

A rapid and efficient multiresidue method that involves using improved QuEChERS method and liquid chromatography-electrospray tandem mass spectrometry (LC-ESI-MS/MS) was developed to measure trace levels of sulfonamides in fish tissue. This proposed method was proven to be a powerful, highly sensitive, and environmentally friendly analytical tool that requires minimal sample preparation. The typical MS/MS fragmentation patterns of the [M+H](+) were 156 m/z, 108 m/z, and 92 m/z. Separation was performed on HC-C18 columns with a gradient elution by using methanol -5mM ammonium acetate containing formic acid (pH 3.5). This method was validated and exhibited favorable performance as well as acceptable accuracy (80.2-93.5%), precision (3.82-8.71%), sensitivity (limits of detection (LODs) 0.43-1.22 µg kg(-1), limits of quantification (LOQs) 1.27-3.71 µg kg(-1); decision limit (CCα) 1.49-10.9 µg kg(-1), detection capability (CCß) 1.71-11.4 µg kg(-1)), and an acceptable matrix effect (-18.2-18.4%). This methodology has been successfully applied in analyzing various fish tissue from local markets.


Assuntos
Fracionamento Químico/métodos , Cromatografia Líquida de Alta Pressão/métodos , Resíduos de Drogas/análise , Espectrometria de Massas por Ionização por Electrospray/métodos , Sulfonamidas/análise , Animais , Limite de Detecção , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Sulfanilamida , Sulfanilamidas , Espectrometria de Massas em Tandem/métodos
4.
J Food Drug Anal ; 23(4): 636-644, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28911479

RESUMO

In this study, a method for determination of cholesterol and four phytosterols by gas chromatography coupled with electron impact ionization mode-tandem mass spectrometry without derivatization in general food was developed. The sample was saponified with 7.5% KOH in methanol. After heating on hot plate and reflux for 60 minutes, the saponified portion was extracted with n-hexane/petroleum ether (50:50, v/v). The extracts were evaporated with rotary evaporator and then redissolved with tetrahydrofuran. The tetrahydrofuran layer was transferred into an injection vial and analyzed by gas chromatography on a 30 m VF-5 column. Limit of quantification was 2 mg/kg. Recoveries of cholesterol and four phytosterols from general food were between 91% and 100%.

5.
Org Biomol Chem ; 9(3): 834-44, 2011 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-21109855

RESUMO

New eunicellin-base diterpenoids, klysimplexins I-T (1-12), were isolated from a cultured soft coral Klyxum simplex. Their structures were elucidated by spectroscopic methods, particularly in 1D and 2D NMR experiments. The absolute stereochemistry of 4 was determined by Mosher's method. Compounds 9 and 12 have been shown to exhibit cytotoxicity toward a limited panel of cancer cell lines. Compounds 2-6, 10 and 11 were found to display significant in vitro anti-inflammatory activity in LPS-stimulated RAW264.7 macrophage cells by inhibiting the expression of the iNOS protein. Compounds 10 and 11 also could effectively reduce the level of COX-2 protein.


Assuntos
Antozoários/química , Diterpenos/química , Animais , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/enzimologia , Camundongos , Modelos Moleculares , Óxido Nítrico Sintase Tipo II/metabolismo
6.
J Environ Monit ; 11(1): 92-9, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19137144

RESUMO

Acute toxic responses as well as uptake and depuration rates for tributyltin (TBT) and dibutyltin (DBT) were examined in the small planktonic shrimp, Acetes intermedius. The 72-h LC(50) values of TBT and DBT for the shrimp were found to be 18.6 and 82.6 microg L(-1) as tin. The uptake rate constants of TBT and DBT in the shrimp were 0.0006 and 0.0002 L g(-1) h(-1), and the corresponding depuration rate constants were 0.0303 and 0.0106 h(-1), respectively. It appears that real-time ambient TBT pollution status can be more closely reflected in this species. The shrimp may serve as a biomonitor to indicate short-term fluctuations in ambient TBT pollution. A field survey was also conducted to distinguish contrasts in butyltin accumulation under different ambient conditions. These observations provide valuable information for the evaluation of TBT pollution status in the environment using A. intermedius as a biomonitor.


Assuntos
Bioensaio/métodos , Decápodes/efeitos dos fármacos , Monitoramento Ambiental/métodos , Poluentes Ambientais/toxicidade , Compostos Orgânicos de Estanho/toxicidade , Compostos de Trialquitina/toxicidade , Animais , Decápodes/metabolismo , Poluentes Ambientais/farmacocinética , Compostos Orgânicos de Estanho/farmacocinética , Testes de Toxicidade Aguda , Compostos de Trialquitina/farmacocinética
7.
J Nat Prod ; 72(3): 465-8, 2009 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-19006372

RESUMO

Chemical investigation of the octocoral Sarcophyton ehrenbergi, collected at the Dongsha Islands, Taiwan, has led to the isolation of a known ceramide (1) and two new cerebrosides, sarcoehrenosides A (2) and B (4), along with three known cerebrosides (3, 5, and 6). The structures of the new compounds were established by spectroscopic and chemical methods. Sarcoehrenoside A (2) differs from previously known marine cerebrosides in that it possesses a rare alpha-glucose moiety. Compounds 1-6 were evaluated for antimicrobial activity against a small panel of bacteria and for anti-inflammatory activity using RAW 264.7 macrophages.


Assuntos
Antozoários/química , Anti-Inflamatórios/isolamento & purificação , Ceramidas/isolamento & purificação , Cerebrosídeos/isolamento & purificação , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Ceramidas/química , Ceramidas/farmacologia , Cerebrosídeos/química , Cerebrosídeos/farmacologia , Enterobacter aerogenes/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Salmonella enteritidis/efeitos dos fármacos , Serratia marcescens/efeitos dos fármacos , Shigella sonnei/efeitos dos fármacos , Yersinia enterocolitica/efeitos dos fármacos
8.
J Immunol ; 178(5): 3023-30, 2007 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-17312148

RESUMO

The genomic organization of the chicken CD8alpha gene was investigated to determine the basis of its polymorphism. Contiguous to the CD8alpha gene we identified multiple DNA blocks possessing sequences homologous to CD8alpha. Gene conversions and recombination over evolutionary time among CD8alpha and these CD8alpha homologous genes seem to account for the observed polymorphism. Furthermore, these CD8alpha-like DNAs encode a distinct multigene family of immunoreceptors that have a charged or polar residue in place of the interspecies-conserved CD8alpha transmembrane proline residue and a short cytoplasmic tail nonhomologous to CD8alpha. The identification of this novel multigene family with an organization reminiscent of human killer Ig-like receptors raises compelling questions on their evolutionary relationship among immunoreceptors.


Assuntos
Antígenos CD8/genética , Galinhas/genética , Evolução Molecular , Família Multigênica/genética , Locos de Características Quantitativas/genética , Animais , Antígenos CD8/imunologia , Linfócitos T CD8-Positivos/imunologia , Galinhas/imunologia , Humanos , Família Multigênica/imunologia , Estrutura Terciária de Proteína/genética , Locos de Características Quantitativas/imunologia , Homologia de Sequência de Aminoácidos
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