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1.
Biochem Biophys Res Commun ; 533(1): 181-187, 2020 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-32958248

RESUMO

In recent years, the obese and overweight population has increased rapidly, which has become a worldwide public health problem. However, effective medication is lacking. Our previous study identified a novel peptide, PDBSN (GLSVADLAESIMKNL), that could significantly restrict adipocyte differentiation in vitro, but its in vivo function has not been determined. Thus, in this study, we encapsulated the peptide into liposomes attached with two ligands (visceral-adipose-tissue-targeting peptide and cell-penetrating peptide) to improve stability and specificity. We then tested the peptide's function in HFD (high-fat diet)-induced obese mice and found that PDBSN could reduce weight gain and improve insulin resistance as well as lipid homeostasis. These results suggest that PDBSN may be a potential candidate for anti-obesity drug discovery.


Assuntos
Fármacos Antiobesidade/uso terapêutico , L-Lactato Desidrogenase/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/tratamento farmacológico , Fragmentos de Peptídeos/uso terapêutico , Proteínas Quinases Ativadas por AMP/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Fármacos Antiobesidade/administração & dosagem , Dieta Hiperlipídica/efeitos adversos , Ativação Enzimática/efeitos dos fármacos , Glucose/metabolismo , Homeostase/efeitos dos fármacos , L-Lactato Desidrogenase/administração & dosagem , Lipossomos , Masculino , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/metabolismo , Fragmentos de Peptídeos/administração & dosagem
2.
Eur J Anaesthesiol ; 26(1): 28-34, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19122548

RESUMO

BACKGROUND AND OBJECTIVE: Postoperative pain therapy is still a problem for clinicians. Continuous basal infusion of drugs combined with standard patient-controlled analgesia (PCA) is considered to be an effective means of postoperative acute pain management. This study was designed to investigate the analgesic efficacy, morphine-sparing effects and side effects of butorphanol delivered as a continuous infusion adjunct to intravenous morphine PCA after abdominal hysterectomy. METHODS: One hundred and eighty-six ASA physical status I-II patients, undergoing total abdominal hysterectomy, were allocated to this randomized double-blind controlled study and assigned to one of two groups. In the butorphanol (n = 96) group, patients received an intravenous loading dose of 10 microg kg(-1) butorphanol followed by infusion of 2 microg kg(-1) h(-1) butorphanol combined with intravenous PCA set at a bolus of 0.02 mg kg(-1) morphine after surgery. The control group (n = 90) received a physiological saline infusion combined with the same morphine PCA. Pain intensity on movement and at rest, sedation, satisfaction with analgesia, morphine consumption and side effects were recorded. RESULTS: A total of 164 patients completed the study. The butorphanol group had analgesia superior to the physiological saline control (P < 0.001). The butorphanol infusion group produced higher sedation ratings (P < 0.001) and better satisfaction (P < 0.05) and a lower incidence of side effects (P < 0.001) with the exception of sweating and dry mouth (P < 0.05) than the physiological saline group. The butorphanol group consumed less morphine over 48 h, 24.6 mg (95% confidence interval, 18.7-46.6), than the physiological saline group, 58.5 mg (95% confidence interval, 41.5-79.2; P = 0.006). There were no differences between urinary catheterization of more than 24 h, first time out of bed and time to discharge to home. CONCLUSION: Basal infusion of butorphanol combined with intravenous morphine PCA in patients undergoing abdominal hysterectomy shows effective analgesia with sedation and fewer side effects.


Assuntos
Analgesia Controlada pelo Paciente , Butorfanol/farmacologia , Histerectomia , Morfina/farmacologia , Butorfanol/administração & dosagem , Butorfanol/efeitos adversos , Combinação de Medicamentos , Feminino , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Morfina/administração & dosagem , Morfina/efeitos adversos
3.
Int J Pharm ; 375(1-2): 89-96, 2009 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-19481694

RESUMO

Resveratrol has been reported to protect several types of cells against beta-amyloid peptide (Abeta) toxicity by scavenging reactive oxygen species (ROS) and inactivating caspase-3. However, other studies found that long-term treatment with resveratrol inhibited cells by inducing ROS generation and activating caspase-3. In the current report, a 48-h incubation of resveratrol at the concentrations of 5 and 10 microM significantly attenuated the viability of PC12 cells and a 12-h pre-incubation of resveratrol did not protect PC12 cells against Abeta exposure (even further inhibited PC12 cells at the concentrations of 10 microM) by acting as a pro-oxidant. Due to the lipophilicity of resveratrol, resveratrol-loaded polymeric micelles basing on amphiphilic block copolymer were developed. Then, the effects of resveratrol-loaded polymeric micelles on the viability and Abeta protection of PC12 cells were investigated. At the equivalent concentrations of 5 and 10 microM resveratrol, a 48-h incubation of resveratrol-loaded nanoparticles did not show toxicity to cells, while 12-h pre-incubation of resveratrol-loaded nanoparticles protected PC12 cells from Abeta-induced damage in a dose dependent manner (1-10 microM) by attenuating intracellular oxidative stress and caspase-3 activity. Further investigations are absolutely needed to evaluate the feasibility and advantages of in vivo applications of resveratrol-loaded nanoparticles.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Antioxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estilbenos/farmacologia , Animais , Antioxidantes/administração & dosagem , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Micelas , Nanopartículas , Células PC12 , Polímeros/química , Ratos , Espécies Reativas de Oxigênio/metabolismo , Resveratrol , Estilbenos/administração & dosagem , Estilbenos/efeitos adversos
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