RESUMO
PURPOSE: The current study investigated the efficacy of Cyclocarya paliurus chloroform extract (CPEC) and its two specific triterpenoids (cyclocaric acid B and cyclocarioside H) on the regulation of glucose disposal and the underlying mechanisms in 3T3-L1 adipocytes. METHODS: Mice and adipocytes were stimulated by macrophages-derived conditioned medium (Mac-CM) to induce insulin resistance. CPEC was evaluated in mice for its ability by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). To investigate the hypoglycemic mechanisms of CPEC and its two triterpenoids, glucose uptake, AMP-activated protein kinase (AMPK) activation, inhibitor of NF-κB kinase ß (IKKß) phosphorylation and insulin signaling transduction were detected in 3T3-L1 adipocytes using 2-NBDG uptake assay and Western blot analysis. RESULTS: Mac-CM, an inflammatory stimulus which induced the glucose and insulin intolerance, increased phosphorylation of IKKß, reduced glucose uptake and impaired insulin sensitivity. CPEC and two triterpenoids improved glucose consumption and increased AMPK phosphorylation under basal and inflammatory conditions. Moreover, CPEC and its two triterpenoids not only enhanced glucose uptake in an insulin-independent manner, but also restored insulin-mediated protein kinase B (Akt) phosphorylation by reducing the activation of IKKß and regulating insulin receptor substrate-1 (IRS-1) serine/tyrosine phosphorylation. These beneficial effects were attenuated by AMPK inhibitor compound C, implying that the effects may be associated with AMPK activation. CONCLUSIONS: CPEC and its two triterpenoids promoted glucose uptake in the absence of insulin, as well as ameliorated IRS-1/PI3K/Akt pathway by inhibiting inflammation. These effects were related to the regulation of AMPK activity.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/efeitos dos fármacos , Glucose/metabolismo , Juglandaceae/química , Extratos Vegetais/química , Triterpenos/química , Células 3T3-L1 , Adipócitos/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Hipoglicemiantes/química , Quinase I-kappa B/metabolismo , Insulina/metabolismo , Resistência à Insulina , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fosforilação , Folhas de Planta/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de SinaisRESUMO
OBJECTIVE: To observe the serum inflammatory and coagulation factors changes and clinical significance following carotid artery stenting. PATIENTS AND METHODS: The expressions of serum inflammatory factors including IL-2, IL-6, IL-8, sICAM-1, hs-CRP, and TNF-α and serum coagulation factors including prothrombin time (PT), active partial thromboplastin time (APTT), fibrinogen (FIB), D-dimer (DD), and fibrin degradation products (FDP) were determined in 92 patients who had undergone carotid artery stenting before, 24h, 48 h, 3 days and 1 week after the surgery. As well, 92 subjects who did not receive stenting were enrolled in the angiography group, amongst whom the same variables were determined. RESULTS: In the stenting group, the expressions of hs-CRP, TNF-α, sICAM-1, IL-6, IL-8, FIB, and DD were significantly increased after the surgery (p < 0.05): hs-CRP reached a peak 48 h after the surgery; TNF-α, sICAM-1, and IL-6 maintained at high levels at days 3-7; and FIB and DD increased 48 h and 3d after the surgery. Compared with the angiography group, the expressions of hs-CRP, TNF-α, sICAM-1, and IL-8 (24h after the surgery) as well as FIB and DD (48 h and 3d after the surgery) were significantly higher in the stenting group. CONCLUSIONS: The hs-CRP, TNF-α, sICAM-1, IL-8, FIB, and DD increased after carotid artery stenting and, therefore, can serve as important factors for monitoring for acute postoperative complications.
Assuntos
Artérias Carótidas/cirurgia , Citocinas/sangue , Stents , Idoso , Feminino , Humanos , Interleucina-6/sangue , Masculino , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologiaRESUMO
This study aimed to investigate the clinical effects and safety review of self-expanding stent surgery in the treatment of extracranial carotid artery stenosis. Seventy-eight patients with carotid artery stenosis were applied with the self-expanding stent for endovascular interventional therapy. Eighty-one stents were implanted into 80 blood vessels of the 78 patients, in which protective umbrellas were used in 56 cases, and the success rate of stent implantation was 100%. The stenosis degree decreased from the preoperative (86.72 ± 9.5%) to the postoperative (13.43 ± 5.62%) stage, and the blood peak velocity of the stenosed vessels decreased from 189.58 ± 13.5 to 83.73 ± 5.61 cm/s. Transient blood pressure and heart rate decreases occurred in 21 cases, continuously low blood pressure and heart rate decreasing occurred in 29 cases, and acute occlusion of the ipsilateral middle cerebral artery occurred in 1 case, which was resolved through thrombolysis and thrombus breaking in time. Over-perfusion symptoms were observed in 13 cases, although without serious complications such as cerebral hemorrhage. The follow-up period continued for 6-32 months, and ultrasonography revealed that 77 cases had no stent-restenosis, while 1 case had restenosis. The application of self-expanding stents had good clinical effects, with fewer complications and higher safety for the treatment of extracranial carotid artery stenosis.
Assuntos
Artérias Carótidas/cirurgia , Estenose das Carótidas/cirurgia , Procedimentos Endovasculares/instrumentação , Stents , Adulto , Idoso , Idoso de 80 Anos ou mais , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/patologia , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/patologia , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , UltrassonografiaRESUMO
Iontophoresis of pulse current with various current intensity, frequency, on/off ratio and duration of treatment was used to facilitate the transdermal delivery of insulin in order to control blood glucose levels in diabetic rats. Male Sprague-Dawley rats were made diabetic by i.p. injection of streptozotocin (65 mg . kg-1 body weight). After two days, diabetic rats were anaesthetized with urethane (as 25% aqueous solution, 1.5 mg . g-1). Both the reservoir electrodes and the receptor electrodes were applied on the abdominal site of the diabetic rats. Iontophoresis was carried out using a prototype transdermal periodic iontophoretic system in order to provide the required direct current with desired pulse modes. The extent of reduction of blood glucose levels was found to be positively correlated with the current intensity, frequency and duration of treatment to some extent. But when the current intensity was over 0.8 mA/cm2 and the frequency was over 3000 Hz, the reduction of blood glucose levels did not continuously increase. Blood glucose levels were found to be better controlled when the on/off ratio of 1 : 1 was used.
Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/sangue , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Absorção Cutânea , Administração Cutânea , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Iontoforese , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Facilitated transdermal delivery of insulin by pulse current iontophoresis was investigated. It was found that pulse current iontophoresis can increase the transdermal permeation rate, and there was a positive correlation between reservoir insulin concentration and skin permeation rate of insulin. Moreover, when the reservoir solution pH (3.6) was below the isoelectric point of insulin (pI 5.2), the transdermal permeation rate of insulin was the highest, 324.3 +/- 33.4 microU/(cm2.h). When the pH of the reservoir solution was brought up to 7.4, the transdermal permeation rate of insulin declined markedly to 143.7 +/- 27.3 microU/(cm2.h). When the reservoir solution pH was close to the isoelectric point of insulin, the transdermal permeation rate of insulin was the lowest, 78.4 +/- 21.9 microU/(cm2.h).