Molecular role of GATA binding protein 4 (GATA-4) in hyperglycemia-induced reduction of cardiac contractility

<p>Abstract</p> <p>Background</p> <p>Diabetic cardiomyopathy, a diabetes-specific complication, refers to a disorder that eventually leads to left ventricular hypertrophy in addition to diastolic and systolic dysfunction. In recent studies, hyperglycemia-induced reactive oxygen species (ROS) in cardiomyocytes have been linked to diabetic cardiomyopathy. GATA binding protein 4 (GATA-4) regulates the expression of many cardio-structural genes including cardiac troponin-I (cTnI).</p> <p>Methods</p> <p>Streptozotocin-induced diabetic rats and H9c2 embryonic rat cardiomyocytes treated with a high concentration of glucose (a D-glucose concentration of 30 mM was used and cells were cultured for 24 hr) were used to examine the effect of hyperglycemia on GATA-4 accumulation in the nucleus. cTnI expression was found to be linked to cardiac tonic dysfunction, and we evaluated the expression levels of cTnI and GATA-4 by Western blot analysis.</p> <p>Results</p> <p>Cardiac output was lowered in STZ-induced diabetic rats. In addition, higher expressions of cardiac troponin I (cTnI) and phosphorylated GATA-4 were identified in these rats by Western blotting. The changes were reversed by treatment with insulin or phlorizin after correction of the blood sugar level. In H9c2 cells, ROS production owing to the high glucose concentration increased the expression of cTnI and GATA-4 phosphorylation. However, hyperglycemia failed to increase the expression of cTnI when GATA-4 was silenced by small interfering RNA (siRNA) in H9c2 cells. Otherwise, activation of ERK is known to be a signal for phosphorylation of serine105 in GATA-4 to increase the DNA binding ability of this transcription factor. Moreover, GSK3β could directly interact with GATA-4 to cause GATA-4 to be exported from the nucleus. GATA-4 nuclear translocation and GSK3β ser9 phosphorylation were both elevated by a high glucose concentration in H9c2 cells. These changes were reversed by tiron (ROS scavenger), PD98059 (MEK/ERK inhibitor), or siRNA of GATA-4. Cell contractility measurement also indicated that the high glucose concentration decreased the contractility of H9c2 cells, and this was reduced by siRNA of GATA-4.</p> <p>Conclusions</p> <p>Hyperglycemia can cause systolic dysfunction and a higher expression of cTnI in cardiomyocytes through ROS, enhancing MEK/ERK-induced GATA-4 phosphorylation and accumulation in the cell nucleus.</p

Natural orifice transluminal endoscopic surgery: A transtracheal approach for the thoracic cavity in a live canine model

BackgroundThe present study aimed to evaluate the performance of transtracheal thoracic exploration and pericardial window creation in a canine survival model.MethodsTransthoracic exploration was performed in 14 dogs. Under general anesthesia, after an incision in the right lateral wall of the middle–lower portion of the trachea was made, a 9-mm metal tube was advanced into the thoracic cavity. For thoracic cavity exploration and pericardial window creation, a flexible bronchoscope was introduced through the metal tube into the thoracic cavity. After thoracoscopy, a Dumon stent (Novatech, Grasse, France) was used to cover the tracheal incision site and facilitate healing. Animals were evaluated by endoscopy 1 and 2 weeks later. Animals were humanely killed, and necropsy was performed 2 weeks after the transtracheal natural orifice transluminal endoscopic surgery.ResultsFourteen dogs underwent transtracheal thoracic exploration lasting for an average of 110 minutes (range, 80–150), with 3 perioperative deaths. At 2 weeks after pericardial window creation, endoscopy revealed normal healing of the tracheal incision sites in all 11 surviving animals. Necropsy on the 11 animals at 2 weeks showed 9 adhesions around the pericardial window and 5 adhesions around the tracheal incision region. No mediastinitis or abscesses could be identified.ConclusionsTranstracheal thoracic exploration is technically feasible. Increasing surgical experience together with improvement in endoscopic techniques will further facilitate the development of natural orifice transluminal endoscopic surgery for thoracic diseases

Spatiotemporal analysis of air pollution and asthma patient visits in Taipei, Taiwan

[[abstract]]Background: Buffer analyses have shown that air pollution is associated with an increased incidence of asthma, but little is known about how air pollutants affect health outside a defined buffer. The aim of this study was to better understand how air pollutants affect asthma patient visits in a metropolitan area. The study used an integrated spatial and temporal approach that included the Kriging method and the Generalized Additive Model (GAM). Results: We analyzed daily outpatient and emergency visit data from the Taiwan Bureau of National Health Insurance and air pollution data from the Taiwan Environmental Protection Administration during 2000-2002. In general, children (aged 0-15 years) had the highest number of total asthma visits. Seasonal changes of PM10, NO2, O3 and SO2 were evident. However, SO2 showed a positive correlation with the dew point (r = 0.17, p < 0.01) and temperature (r = 0.22, p < 0.01). Among the four pollutants studied, the elevation of NO2 concentration had the highest impact on asthma outpatient visits on the day that a 10% increase of concentration caused the asthma outpatient visit rate to increase by 0.30% (95% CI: 0.16%??.45%) in the four pollutant model. For emergency visits, the elevation of PM10 concentration, which occurred two days before the visits, had the most significant influence on this type of patient visit with an increase of 0.14% (95% CI: 0.01%??.28%) in the four pollutants model. The impact on the emergency visit rate was non-significant two days following exposure to the other three air pollutants. Conclusion: This preliminary study demonstrates the feasibility of an integrated spatial and temporal approach to assess the impact of air pollution on asthma patient visits. The results of this study provide a better understanding of the correlation of air pollution with asthma patient visits and demonstrate that NO2 and PM10 might have a positive impact on outpatient and emergency settings respectively. Future research is required to validate robust spatiotemporal patterns and trends

First- and Second-trimester Down Syndrome Screening: Current Strategies and Clinical Guidelines

SummaryDown syndrome (DS) is the most common human disease caused by a structural chromosome defect. The original screening test for DS was maternal age or a history of a previously affected infant. Maternal serum screening has been incorporated into routine prenatal checkup in Taiwan since 1994. We used free β-human chorionic gonadotropin and α-fetoprotein (double test) as the serum markers, and this was carried out between the 15 to 20th week of gestation. The overall detection rate was 56% and was compatible with studies of Caucasian populations. The impact of double tests in Taiwan has shown itself by a dramatic lowering of the rate of DS live birth from 0.63 before screening to 0.16 per 1,000 live births at present. However, because of its relatively low detection rate and poor cost-effectiveness, the double test is not justified as a routine screening tool currently. First-trimester combined test is now becoming more widely available and provides increased sensitivity when detecting DS; it has a detection rate of approximately 85% with a false-positive rate of 5%. Nuchal translucency measurement requires ongoing quality control and sufficient certificated obstetricians; therefore, first-trimester ultrasound is limited only in designated centers. The quadruple test, having comparable detection rate, should be considered for incorporation into second-trimester screening in Taiwan in the near future. Other screening approaches and combinations have also been utilized in the Western countries. In this review, we outline the various options with respect to DS screening and hope that this will provide practical information for physicians offering such screenings. [Taiwan J Obstet Cynecol 2008;47(2):157-1 62

Second-trimester Maternal Serum Quadruple Test for Down Syndrome Screening: A Taiwanese Population-based Study

SummaryObjectiveTo assess the usefulness of quadruple test screening for Down syndrome in Taiwan.Materials and MethodsMaternal serum concentrations of a-fetoprotein, human chorionic gonadotropin, unconjugated estriol, and inhibin A were measured in 21,481 pregnant women from 15 to 20 weeks of gestation.ResultsOf the 21,481 women, 977 returned values greater than the high-risk cut-off value (1 in 270). Most of these women (86.2%) decided to have an invasive procedure for genetic diagnosis. Nine cases of Down syndrome and 19 cases of other chromosomal anomalies were detected prenatally. Two children with Down syndrome were diagnosed after delivery even though a low estimated risk was determined following the quadruple test. The detection rate was 81.8% (nine out of 11 cases), with a 4.4% false-positive rate. The median multiple of the median value for a-fetoprotein, human chorionic gonadotropin, unconjugated estriol and inhibin A were 0.87, 2.34, 0.77 and 2.16, respectively, in affected cases.ConclusionThis is the first study of the quadruple test for Down syndrome in a Chinese population. Our findings suggested that the second-trimester quadruple test provides an effective screening tool for Down syndrome in Taiwan

Concurrent image-guided intensity modulated radiotherapy and chemotherapy following neoadjuvant chemotherapy for locally advanced nasopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>To evaluate the experience of induction chemotherapy followed by concurrent chemoradiationwith helical tomotherapy (HT) for nasopharyngeal carcinoma (NPC).</p> <p>Methods</p> <p>Between August 2006 and December 2009, 28 patients with pathological proven nonmetastatic NPC were enrolled. All patients were staged as IIB-IVB. Patients were first treated with 2 to 3 cycles of induction chemotherapy with EP-HDFL (Epirubicin, Cisplatin, 5-FU, and Leucovorin). After induction chemotherapy, weekly based PFL was administered concurrent with HT. Radiation consisted of 70 Gy to the planning target volumes of the primary tumor plus any positive nodal disease using 2 Gy per fraction.</p> <p>Results</p> <p>After completion of induction chemotherapy, the response rates for primary and nodal disease were 96.4% and 80.8%, respectively. With a median follow-up after 33 months (Range, 13-53 months), there have been 2 primary and 1 nodal relapse after completion of radiotherapy. The estimated 3-year progression-free rates for local, regional, locoregional and distant metastasis survival rate were 92.4%, 95.7%, 88.4%, and 78.0%, respectively. The estimated 3-year overall survival was 83.5%. Acute grade 3, 4 toxicities for xerostomia and dermatitis were only 3.6% and 10.7%, respectively.</p> <p>Conclusion</p> <p>HT for locoregionally advanced NPC is feasible and effective in regard to locoregional control with high compliance, even after neoadjuvant chemotherapy. None of out-field or marginal failure noted in the current study confirms the potential benefits of treating NPC patients by image-guided radiation modality. A long-term follow-up study is needed to confirm these preliminary findings.</p