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We report a unique phenomenon in which liquid metal droplets (LMDs) under a pure ac electric field pump fluid. Unlike the directional pumping that occurs upon reversing the electric field polarity under a dc signal, this phenomenon allows the direction of fluid motion to be switched by simply shifting the position of the LMD within the cylindrical chamber. The physical mechanism behind this phenomenon has been termed Marangoni flow, caused by nonlinear electrocapillary stress. Under the influence of a localized, asymmetric ac electric field, the polarizable surface of the position-offset LMD produces a net time-averaged interfacial tension gradient that scales with twice the field strength, and thus pumps fluid unidirectionally. However, the traditional linear RC circuit polarization model of the LMD/electrolyte interface fails to capture the correct pump-flow direction when the thickness of the LMD oxide skin is non-negligible compared to the Debye length. Therefore, we developed a physical description by treating the oxide layer as a distributed capacitance with variable thickness and connected with the electric double layer. The flow profile is visualized via microparticle imaging velocimetry, and excellent consistency is found with simulation results obtained from the proposed nonlinear model. Furthermore, we investigate the effects of relevant parameters on fluid pumping and discuss a special phenomenon that does not exist in dc control systems. To our knowledge, no previous work addresses LMDs in this manner and uses a zero-mean ac electric field to achieve stable, adjustable directional pumping of a low-conductivity solution.
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The failure of reproductive success in polycystic ovary syndrome (PCOS) patients could be in part due to endometrial dysfunction. However, no studies have investigated any causality between androgen, androgen receptor (AR) expression, and adenosine monophosphate activated protein kinase (AMPK) activation in the endometrium under physiological and pathological conditions. In the present study, we show that 1) endometrial AR expression levels fluctuate in non-PCOS and PCOS patients during the menstrual cycle; 2) the menstrual phase-dependent alteration of p-AMPKα expression occurs in non-PCOS patients but not in PCOS patients; 3) AR expression is higher in PCOS patients than non-PCOS patients during hyperplasia while AMPKα activation (indicated by the ratio of p-AMPKα to AMPKα); and 4) co-localization of AR and Ki-67 in epithelial cell nuclei is observed in endometrial hyperplasia. Importantly, using in vitro human tissue culture and an in vivo 5α-dihydrotestosterone-treated rat model, we show that the action of androgen on AMPKα activation is likely mediated through nuclear AR, especially in epithelial cells. Collectively, we present evidence that AR expression and AMPKα activation depend on menstrual cycle phase and the presence of PCOS, and the data suggest that AR-mediated regulation of AMPKα activation might play a role in the development of endometrial hyperplasia.
Assuntos
Adenilato Quinase/metabolismo , Endométrio/metabolismo , Síndrome do Ovário Policístico/metabolismo , Receptores Androgênicos/metabolismo , Animais , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Di-Hidrotestosterona/farmacologia , Endométrio/enzimologia , Feminino , Flutamida/farmacologia , Humanos , Técnicas In Vitro , Antígeno Ki-67/metabolismo , Fosforilação , Síndrome do Ovário Policístico/enzimologia , Ratos , Ratos WistarRESUMO
Conflicting results have been reported regarding whether or not insulin-regulated glucose transporter 4 (GLUT4) is expressed in human and rodent endometria. There is an inverse relationship between androgen levels and insulin-dependent glucose metabolism in women. Hyperandrogenemia, hyperinsulinemia, and insulin resistance are believed to contribute to endometrial abnormalities in women with polycystic ovary syndrome (PCOS). However, it has been unclear in previous studies if endometrial GLUT4 expression is regulated by androgen-dependent androgen receptors (ARs) and/or the insulin receptor/Akt/mTOR signaling network. In this study, we demonstrate that GLUT4 is expressed in normal endometrial cells (mainly in the epithelial cells) and is down-regulated under conditions of hyperandrogenemia in tissues from PCOS patients and in a 5α-dihydrotestosterone-induced PCOS-like rat model. Western blot analysis revealed reduced endometrial GLUT4 expression and increased AR expression in PCOS patients. However, the reduced GLUT4 level was not always associated with an increase in AR in PCOS patients when comparing non-hyperplasia with hyperplasia. Using a human tissue culture system, we investigated the molecular basis by which GLUT4 regulation in endometrial hyperplasia tissues is affected by metformin in PCOS patients. We show that specific endogenous organic cation transporter isoforms are regulated by metformin, and this suggests a direct effect of metformin on endometrial hyperplasia. Moreover, we demonstrate that metformin induces GLUT4 expression and inhibits AR expression and blocks insulin receptor/PI3K/Akt/mTOR signaling in the same hyperplasia human tissues. These findings indicate that changes in endometrial GLUT4 expression in PCOS patients involve the androgen-dependent alteration of AR expression and changes in the insulin receptor/PI3K/Akt/mTOR signaling network.
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OBJECTIVE: To evaluate the perforation, circumferential resection margin (CRM) and postoperative perineal wound complications after extralevator abdominoperineal excision (ELAPE) and conventional abdominoperineal excision (APE) for low rectal cancer by using systematic review method. METHODS: The Cochrane Library, PubMed, EMbase, CNKI and VIP database were searched for literatures in which ELAPE and APE were compared for the treatment of low rectal cancer. Meta-analysis was performed to deal with data extracted by Cochrane Systematic Reviews methods. RESULTS: Six studies met the inclusion criteria including one randomized control study and five non-randomized control studies with a total of 656 cases including 346 cases of ELAPE and 310 cases of APE. Meta-analysis showed a lower positive CRM rate (RR=0.48, 95%CI:0.36-0.65) and a lower local recurrence rate (RR=0.43, 95%CI:0.19-0.99) in ELAPE compared with APE. There were no significant differences in operative perforation rate (RR=0.45, 95%CI:0.15-1.37) and post-operative perineal wound complications rate (RR=1.20, 95%CI:0.57-2.50) between the two surgical procedures. CONCLUSION: ELAPE is associated with lower rates of positive CRM and local recurrence compared with APE.
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Períneo/cirurgia , Neoplasias Retais/cirurgia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND: Intra-operative cholangiography has been shown to be a sensitive and specific method of demonstrating bile duct stones. This study investigated the feasibility, safety, and clinical value of selective trans-cystic intra-operative cholangiography in primary suture following three-port laparoscopic common bile duct exploration, and identified the factors that positively predict the presence of common bile duct stones. METHODS: From January 2008 to January 2011, 252 of 1013 patients undergoing laparoscopic cholecystectomy received selective trans-cystic intra-operative cholangiography and primary suture following three-port laparoscopic common bile duct exploration. Their clinical data were analyzed retrospectively. RESULTS: All operations were successful and none was converted to open surgery. The intra-operative cholangiography time was (8.3 ± 2.5) minutes, and the operative duration was (105.4 ± 23.1) minutes. According to selective intra-operative cholangiography, the positive predictive values of current jaundice, small gallstones (< 0.5 cm) and dilated cystic duct (> 0.3 cm), dilated common bile duct (> 0.8 cm), history of jaundice or gallstone pancreatitis, abnormal liver function test, and preoperative demonstration of suspected common bile duct stones on imaging were 87%, 25%, 42%, 15%, 32%, and 75% for common bile duct stones, respectively. Patients with several factors suggestive of common bile duct stones yielded higher numbers of positive cholangiograms. Unexpected stones were found in 13 patients (5.2%) by intra-operative cholangiography. The post-operative hospital stay was (4.7 ± 2.2) days. Post-operative bile leakage occurred in two cases, and these patients recovered by simple drainage for 3 - 7 days without re-operation. Of the 761 patients who underwent laparoscopic cholecystectomy alone, 5 (0.7%) presented with a retained common bile duct stone requiring intervention. The median follow-up was 12 months, and only one patient who once suffered from bile leakage presented with obstructive jaundice due to bile duct stenosis 6 months postoperatively. The other patients recovered without any serious complications. CONCLUSIONS: Selective intra-operative cholangiography yields acceptably high positive results. It is a safe, effective, and minimally invasive approach in patients with suspected choledocholithiasis and primary suture following three-port laparoscopic common bile duct exploration.
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Colangiografia/métodos , Coledocolitíase/diagnóstico por imagem , Ducto Colédoco/diagnóstico por imagem , Cálculos Biliares/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Colecistectomia Laparoscópica/métodos , Coledocolitíase/cirurgia , Ducto Colédoco/cirurgia , Feminino , Cálculos Biliares/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: To investigate the inhibitory effect of the mammalian target of rapamycin (mTOR) inhibitor, sirolimus on expression of hypoxia-inducible factor (HIF)1alpha protein and growth of ovarian carcinoma in an athymic mouse xenogeneic transplant model of ovarian cancer. METHODS: Four groups of female nude mice were inoculated subcutaneously with SKOV3 cells. After inoculation, mice were treated with saline, rapamycin alone, paclitaxel alone and sirolimus + paclitaxel. In each tumor protein expressions of HIF-1alpha, bcl-2 and apoptosis were determined by immunohistochemistry and RT-PCR. RESULTS: In sirolimus and sirolimus + paclitaxel groups protein expression of HIF-1alpha was inhibited. Tumor burden in rapamycin alone, sirolimus + paclitaxel, and paclitaxel alone was reduced by 47.9% (P < 0.05), 51.0% (P < 0.05), and 31.8% (P > 0.05) respectively compared with controls. Cell apoptosis inder in sirolimus alone (36), sirolimus + paclitaxel (40), paclitaxel alone (22), increased compared with control (15), while expression of bcl-2 decreased compared with control. CONCLUSION: Sirolimus inhibited protein expression of HIF-1alpha, increased tumor apoptosis and decreased tumor growth.
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Neoplasias Ovarianas/metabolismo , Paclitaxel/farmacologia , Sirolimo/farmacologia , Fatores de Transcrição/biossíntese , Animais , Antibióticos Antineoplásicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Feminino , Subunidade alfa do Fator 1 Induzível por Hipóxia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Neoplasias Ovarianas/patologia , Fatores de Transcrição/genéticaRESUMO
OBJECTIVE: To investigate the correlation of hypoxia-inducible factor (HIF)-1alpha and vascular endothelial growth factor (VEGF) or micro-vessel density (MVD). METHODS: The ovarian cancer cell line SKOV3 was transplanted into nude mice to form xenogeneic tumor. Mice were treated with rapamycin 4 mg/kg, sulindac 100 mg/(kg.d) and saline 200 microl respectively. Expression of HIF-1alpha and VEGF proteins and MVD were determined by immunohistochemistry. The mRNA of Glut1 and VEGF was studied by RT-PCR. RESULTS: The positive expression of HIF-1alpha and VEGF was moderate to strong, and MVD was high (31 +/- 8) in control group. In rapamycin treated group, the expression of HIF-1alpha was inhibited to weak positive or negative (P < 0.05), the VEGF protein and mRNA expression decreased (P < 0.05), MVD was also suppressed to a low level (13 +/- 5). There was a significant correlation between HIF-1alpha expression and VEGF expression (by Spearman's coefficient r = 0.8264, P < 0.01), and MVD (r = 0.4842, P < 0.05). CONCLUSIONS: HIF-1alpha protein can regulate VEGF protein and its mRNA expressions. It correlates with MVD in ovarian tumor tissue.