Activation of spleen tyrosine kinase is required for TNF-α-induced endothelin-1 upregulation in human aortic endothelial cells

AbstractEndothelin-1 (ET-1) promotes atherosclerosis. We tested whether spleen tyrosine kinase (Syk) mediates tumor necrosis factor-α (TNF-α)-induced ET-1 upregulation in human aortic endothelial cells (HAECs) and sought to identify the signal pathways involved. TNF-α-induced reactive oxygen species (ROS) activated Syk and phosphatidylinositol 3-kinase (PI3K), which was required for the activation of AP-1 and subsequent ET-1 gene transcription. ROS mediated c-Jun NH2-terminal kinase (JNK) is also required for AP-1 activation, but Syk and PI3K regulated AP-1 activation independently of JNK. Through regulation of ET-1 production, Syk could be implicated in atherosclerosis

Genetic Effects of FTO and MC4R Polymorphisms on Body Mass in Constitutional Types

Sasang constitutional medicine (SCM), a Korean tailored medicine, categorizes human beings into four types through states of physiological imbalances and responsiveness to herbal medicine. One SCM type susceptible to obesity seems sensitive to energy intake due to an imbalance toward preserving energy. Common variants of fat mass and obesity associated (FTO) and melanocortin 4 receptor (MC4R) genes have been associated with increased body mass index (BMI) by affecting energy intake. Here, we statistically examined the association of FTO and MC4R polymorphisms with BMI in two populations with 1370 Koreans before and after SCM typing, and with the lowering of BMI in 538 individuals who underwent a 1-month lifestyle intervention. The increased BMI replicated the association with FTO haplotypes (effect size ≃ 1.1 kg/m2) and MC4R variants (effect size ≃ 0.64 kg/m2). After the lifestyle intervention, the carriers of the haplotype represented by the minor allele of rs1075440 had a tendency to lose more waist-to-hip ratio (0.76%) than non-carriers. The constitutional discrepancy for the accumulation of body mass by the effects of FTO and/or MC4R variants seemed to reflect the physique differences shown in each group of SCM constitutional types. In conclusion, FTO and MC4R polymorphisms appear to play an important role in weight gain, while only FTO variants play a role in weight loss after lifestyle intervention. Different trends were observed among individuals of SCM types, especially for weight gain. Therefore, classification of individuals based on physiological imbalance would offer a good genetic stratification system in assessing the effects of obesity genes

Effect of 457 nm Diode-Pumped Solid State Laser on the Polymerization Composite Resins: Microhardness, Cross-Link Density, and Polymerization Shrinkage

Objective: The purpose of the present study was to test the usefulness of 457 nm diode-pumped solid state (DPSS) laser as a light source to cure composite resins. Materials and methods: Five different composite resins were light cured using three different light-curing units (LCUs): a DPSS 457 nm laser (LAS), a light-emitting diode (LED), and quartz-tungsten-halogen (QTH) units. The light intensity of LAS was 560 mW/cm2, whereas LED and QTH LCUs was ∼900 mW/cm2. The degree of polymerization was tested by evaluating microhardness, cross-link density, and polymerization shrinkage. Results: Before water immersion, the microhardness of laser-treated specimens ranged from 40.8 to 84.7 HV and from 31.7 to 79.0 HV on the top and bottom surfaces, respectively, and these values were 3.3–23.2% and 2.9–31.1% lower than the highest microhardness obtained using LED or QTH LCUs. Also, laser-treated specimens had lower top and bottom microhardnesses than the other LCUs treated specimens by 2.4–19.4% and 1.4–27.8%, respectively. After ethanol immersion for 24 h, the microhardness of laser-treated specimens ranged from 20.3 to 63.2 HV on top and bottom surfaces, but from 24.9 to 71.5 HV when specimens were cured using the other LCUs. Polymerization shrinkage was 9.8–14.7 μm for laser-treated specimens, and these were significantly similar or lower (10.2–16.0 μm) than those obtained using the other LCUs. Conclusions: The results may suggest that the 457 nm DPSS laser can be used as a light source for light-curing dental resin composites

Recurrent Infective Endocarditis Associated With Pyogenic Spondylodiskitis

Infective endocarditis is a life-threatening condition caused by microbial infection of the heart's endocardial surface. This condition can also be associated with bacterial infections of other organs. We experienced an unusual case of recurrent infective endocarditis associated with pyogenic spondylodiskitis. A 70-year-old man presented with persistent fever and lower back pain visited our hospital. The patient had a past history of recurrent infective endocarditis. He was diagnosed with infective endocarditis again based on clinical symptoms and echocardiographic findings. Magnetic resonance imaging was used to evaluate lower back pain, which showed acute spondylodiskitis on L3 and L4 vertebrae. The patient completely recovered following four weeks of antibiotic therapy

Ectodomain Shedding of RAGE and TLR4 as a Negative Feedback Regulation in High-Mobility Group Box 1-Activated Aortic Endothelial Cells

Background/Aims: High-mobility group box 1 (HMGB1) elicits inflammatory responses through interactions with the receptor for advanced glycation end products (RAGE) and toll-like receptor 4 (TLR4). We investigated how RAGE and TLR4 expressions are regulated after HMGB1 stimulation in cultured human aortic endothelial cells (HAECs). Methods: RAGE and TLR4 expressions were analyzed by Western blot analysis and immunofluorescence staining. A disintegrin and metalloprotease 17 (ADAM17) activity was measured using a fluorogenic substrate. Results: Upon treatment with HMGB1, both RAGE and TLR4 began to decrease in cell lysate and remained decreased up to 24 h. The decrease in cellular RAGE and TLR4 was accompanied by an increase of N-terminal fragment of RAGE and TLR4 in culture supernatant, indicating ectodomain shedding of the receptors. HMGB1 activated p38 mitogen-activated protein kinase (p38 MAPK) and ADAM17, while HMGB1-induced ADAM17 activation was inhibited by SB203580, a p38 MAPK inhibitor. HMGB1-induced ectodomain shedding of RAGE and TLR4 was prevented by siRNA depletion of ADAM17 as well as TAPI-2, an inhibitor of ADAM family, and SB203580. HMGB1 pretreatment abolished p38 MAPK activation in response to 2nd HMGB1 stimulation. In the cells depleted of ADAM17, HMGB1-induced p38 MAPK activation was prolonged. siRNA depletion of RAGE, but not TLR4, suppressed HMGB1-induced p38 MAPK activation. Conclusion: In response to HMGB1 stimulation, HAECs rapidly undergo ectodomain shedding of RAGE and TLR4, and thereby become insensitive to further HMGB1 stimulation. ADAM17, activated through RAGE-p38 MAPK pathway, is implicated in the ectodomain cleavage of the receptors

Type 2 Myocardial Infarction Following Generalized Tonic-Clonic Seizure

Myocardial infarction is diagnosed when blood levels of biomarkers are increased in the clinical setting of acute myocardial ischemia. Among the biomarkers, troponin I is the preferred biomarker indicative of myocardial necrosis. It is tissue specific for the heart. Myocardial infarction is rarely reported following seizure. We report a case of elevated troponin I in a patient after an episode of generalized tonic-clonic seizure. The diagnosis was type 2 myocardial infarction

Effect of light-curing units on the thermal expansion of resin nanocomposites

Purpose—To examine the thermal expansion of resin nanocomposites after light-curing using different light-curing units. Methods—Four different resin nanocomposites and four different light-curing units [quartztungsten- halogen (QTH), light emitting diode (LED), laser, and plasma arc] were chosen. Metal dies were filled with resin to make specimens and light-cured. The light intensity and light-curing time of the QTH and LED light-curing units were 1000 mW/cm2 and 40 seconds, 700 mW/cm2 and 40 seconds for the laser, and 1600 mW/cm2 and 3 seconds for the plasma arc. The coefficient of thermal expansion (CTE) was evaluated using a thermomechanical analyzer (TMA) at temperatures ranging from 30–80°C. Results—The CTE of the resin nanocomposites tested ranged from 28.5 to 65.8 (×10−6/°C), depending on the product and type of light-curing unit used. Among the specimens Grandio showed the lowest CTE. The specimens cured using the plasma arc unit (Apollo 95E) showed the highest CTE. There was a linear correlation between the CTE and filler content (vol%) (R: −0.94~ −0.99 depending on the light-curing unit). The results may suggest a careful selection of the lightcuring unit because there was more expansion in the specimens cured using the plasma arc unit than those cured by the other units. (Am J Dent 2010;23:331–334)

Progression of Prostate Cancer Despite an Extremely Low Serum Level of Prostate-Specific Antigen

A 61-year-old man who had been diagnosed with prostate cancer 9 years ago and had been treated with pelvic irradiation and intermittent androgen deprivation therapy visited the emergency room because of back pain and weakness in both legs. Spine magnetic resonance imaging showed a lumbar epidural mass and spine metastasis. The whole-body workup revealed multiple metastases to the lymph nodes, bone, liver, and lung. The serum prostate-specific antigen was 0.02 ng/ml. He underwent laminectomy, posterior fixation, and epidural mass excision, and metastatic adenocarcinoma from the prostate was diagnosed. The patient underwent 1 cycle of docetaxel-based chemotherapy. More chemotherapy could not be done because of his general weakness. The patient died one month later of multiple organ failure