Role of G{alpha}12 and G{alpha}13 as Novel Switches for the Activity of Nrf2, a Key Antioxidative Transcription Factor

G{alpha}12 and G{alpha}13 function as molecular regulators responding to extracellular stimuli. NF-E2-related factor 2 (Nrf2) is involved in a protective adaptive response to oxidative stress. This study investigated the regulation of Nrf2 by G{alpha}12 and G{alpha}13. A deficiency of G{alpha}12, but not of G{alpha}13, enhanced Nrf2 activity and target gene transactivation in embryo fibroblasts. In mice, G{alpha}12 knockout activated Nrf2 and thereby facilitated heme catabolism to bilirubin and its glucuronosyl conjugations. An oligonucleotide microarray demonstrated the transactivation of Nrf2 target genes by G{alpha}12 gene knockout. G{alpha}12 deficiency reduced Jun N-terminal protein kinase (JNK)-dependent Nrf2 ubiquitination required for proteasomal degradation, and so did G{alpha}13 deficiency. The absence of G{alpha}12, but not of G{alpha}13, increased protein kinase C {delta} (PKC {delta}) activation and the PKC {delta}-mediated serine phosphorylation of Nrf2. G{alpha}13 gene knockout or knockdown abrogated the Nrf2 phosphorylation induced by G{alpha}12 deficiency, suggesting that relief from G{alpha}12 repression leads to the G{alpha}13-mediated activation of Nrf2. Constitutive activation of G{alpha}13 promoted Nrf2 activity and target gene induction via Rho-mediated PKC {delta} activation, corroborating positive regulation by G{alpha}13. In summary, G{alpha}12 and G{alpha}13 transmit a JNK-dependent signal for Nrf2 ubiquitination, whereas G{alpha}13 regulates Rho-PKC {delta}-mediated Nrf2 phosphorylation, which is negatively balanced by G{alpha}12

CO-COMBUSTION OF KOREAN ANTHRACITE WITH VARIOUS FUELS IN A COMMERCIAL CIRCULATING FLUIDIZED BED BOILER

The effect of co-combustion of various fuels such as bituminous coal, imported anthracite, RDF and wood pellet with Korean anthracite on the combustion and environmental performance was observed in the commercial CFB boiler. The temperatures in the furnace and cyclones exits decreased with increasing the cocombustion ratio of the bituminous coal, which could achieve more stable operation of the CFB boiler. During Co-combustion of the RDF and wood pellets, the temperature of the furnace exit increased slightly with due to volatiles re-combustion which could restrict to increase the co-combustion ratio of the RDF and wood pellets in the CFB boiler. It was limited for the electrostatic precipitator (EP) to maintain the stable operation above 5% of the RDF co-combustion ratio according to decrease of the output voltages of the EP collecting plate. High content of CaO in the RDF and the wood pellet made the required limestone flow rates decrease. The emissions NOx, HCl and dioxin during co-combustion of the RDF and wood pellets did not change appreciably when compared with firing only Korean anthracite, which were also low enough to meet Korean regulation limits. On the other hand, chlorine content in the ashes emitted from the boiler increased gradually with increasing the RDF co-combustion ratio because of absorption by limestone. The co-combustion of various fuels with Korean anthracite in the commercial CFB boiler was found to be of great use up to a certain co-combustion ratio of each fuel without the technical and environmental problems

Effect of beraprost sodium on arterial stiffness in patients with type 2 diabetic nephropathy

Trial registration : ClinicalTrials.gov number NCT01796418Background : Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD). Cardiovascular (CV) complications are the most common cause of death among ESRD patients. Beraprost sodium (BPS) is a prostacyclin analog with vasodilatory and antiplatelet effects. Methods : This is a multicenter prospective, randomized, double-blind, placebo-controlled trial to determine whether treatment with BPS improves arterial stiffness in patients with type 2 diabetic nephropathy. A total of 102 participants with type 2 diabetic nephropathy will be screened, enrolled, and randomly assigned to receive either 80 μg BPS or placebo daily for 12 weeks. The primary outcome is the change in brachial-ankle pulse wave velocity between baseline and after 12 weeks of medication use. The secondary outcomes will include changes in the ankle-brachial index, the urine albumin to creatinine ratio, the estimated glomerular filtration rate, lipid profiles, and blood pressure from baseline to after treatment. Discussion : This clinical trial is the first to investigate the effects of BPS on changes in CV biomarkers, albuminuria, renal function, and lipid profiles in patients with diabetic nephropathy.Peer Reviewe

The effects of a 12-week jump rope exercise program on abdominal adiposity, vasoactive substances, inflammation, and vascular function in adolescent girls with prehypertension

Introduction Childhood obesity is strongly associated with cardiovascular disease (CVD) development. It is necessary to combat unfavorable outcomes of obesity at a young age by utilizing effective interventions, such as exercise. Purpose We sought to examine the effects of a jump rope exercise program on CVD risk factors, including body composition, vasoactive substances, inflammation, and vascular function in prehypertensive adolescent girls. Methods Forty girls (age 14–16) were recruited and randomly assigned to a jump rope exercise group (EX, n = 20) or control group (CON, n = 20). Body composition, nitrate and nitrite levels, endothelin-1 (ET-1), C-reactive protein (CRP), systolic blood pressure and diastolic blood pressure (SBP, DBP), and arterial stiffness were measured before and after 12 weeks. Results There were significant group by time interactions following the 12-week program for body composition (from 33.8 ± 3.6 to 30.2 ± 3.1%), central adiposity (from 86.4 ± 4 to 83.3 ± 5 cm), SBP (from 126 ± 3.3 to 120 ± 2.1 mmHg), and brachial-to-ankle pulse wave velocity (from 8.2 ± 1.0 to 7.4 ± 0.2 m/s). Nitrate/nitrite levels increased (from 54.5 ± 5.1 to 57.2 ± 5.2 µmol) along a reduction in CRP levels (from 0.5 ± 0.4 to 0.2 ± 0.1 mg/L). There were no significant changes in ET-1 (P = 0.22). Conclusions These findings indicate that jump rope exercise may be an effective intervention to improve these CVD risk factors in prehypertensive adolescent girls. Jumping rope is an easily accessible exercise modality that may have important health implications for CVD prevention in younger populations

CD44 Disruption Attenuates Murine Hepatic Ischemia/Reperfusion Injury

Neutrophil adhesion and migration are critical in hepatic ischemia/reperfusion (I/R) injury. Despite very strong preclinical data, recent clinical trials failed to show a protective effect of anti-adhesion therapy in reperfusion injury. Therefore, the aim of this study was to assess the role of CD44 in neutrophil infiltration and liver injury from hepatic I/R. In this study, using a partial hepatic ischemic model in vivo, we determined the potential role of CD44 in neutrophil infiltration and liver injury from I/R. Reperfusion caused significant hepatocellular injury as it was determined by plasma ALT levels and liver histopathology. The injury was associated with a marked neutrophil recruitment and CD44 expression into the ischemic livers. Administration of anti-CD44 antibody to mice reduced the infiltration of neutrophil into the ischemic tissue, associated with liver function preservation. These results support crucial roles of CD44 in neutrophil recruitment and infiltration leading to liver damage in hepatic I/R injury. Moreover, they provide the rationale for targeting to CD44 as a potential therapeutic approach in liver I/R injury

Combined exercise training reduces blood pressure, arterial stiffness, and insulin resistance in obese prehypertensive adolescent girls

Childhood obesity is strongly linked to pathological processes for cardiovascular diseases in later adulthood. Obese adolescent girls with high blood pressure (BP) are reported to have increased arterial stiffness, which is associated with the development of hypertension and atherosclerosis. The present study sought to examine the impact of combined resistance and aerobic exercise (CRAE) training on BP, brachial-ankle pulse wave velocity (baPWV), insulin resistance (IR), and body composition in obese prehypertensive girls. Forty girls (age, 15 ± 1 years; systolic BP, 132 ± 2 mmHg, diastolic BP, 80 ± 5 mmHg) were randomly assigned to either a combined exercise (EX, n = 20) or no exercise group (CON, n = 20). The EX group performed CRAE for 12 weeks, 3 times per week. BP, baPWV, blood nitrite/nitrate, endothelin-1 (ET-1), homeostasis model assessment for insulin resistance (HOMA-IR), and body composition were measured before and after the exercise intervention. BP (∆-7.3 ± 2.67 mmHg), baPWV (∆-1.23 ± 0.49 m/s), ET-1 (∆-14.35 ± 1.76 μmol/mL), nitrite/nitrate (∆0.5 ± 0.09 μM), HOMA-IR (∆-1.4 ± 0.07), percent body fat (∆-1.35 ± 0.9%), and waist circumference were significantly improved (P \u3c 0.05) in the EX group after 12 weeks of training versus the CON group. These findings indicate that 12 weeks of CRAE improves BP, HOMA-IR, and arterial stiffness and reduces central adiposity in obese adolescent girls with prehypertension. Thus, this study provides evidence that CRAE can be a useful therapeutic treatment for high BP, IR, and central adiposity, thereby reducing the likelihood of pathological development for cardiovascular diseases in later adulthood

Acute Spontaneous Subdural Hematoma of Arterial Origin

Acute spontaneous subdural hematoma (SDH) of arterial origin is very rare. We report a case of acute spontaneous SDH that showed contrast media extravasation from cortical artery on angiograms. A 58-year-old male patient developed sudden onset headache and right hemiparesis. Brain CT scan demonstrated acute SDH at left convexity. The patient was drowsy mentality on admission. He had no history of head trauma. Cerebral angiography was performed and revealed a localized extravasation of the contrast media from distal cortical MCA branch. After angiography, the patient deteriorated to comatose mentality. Decompressive craniectomy for removal of SDH was performed. We verified the arterial origin of the bleeding and coagulated the bleeding focus. The histological diagnosis was aneurysmal artery. He recovered after surgery with mild disability. In a case of acute spontaneous SDH, the possibility of a cortical artery origin should be considered

Glutaric Aciduria Type 1 in Korea: Report of Two Novel Mutations

Glutaric aciduria type I (GA I) is an autosomal recessive disorder caused by a deficiency of glutaryl-CoA dehydrogenase. Although over 400 patients confirmed as GA I have been reported, reports from the Asian population had contributed to the minor proportion. We recently diagnosed two cases of GA I confirmed with mutational analysis. Here, we present their rather atypical clinical presentations with genetic characteristics for the first time in Korea. Profound developmental delay from birth, association of hearing loss, and neurological improvement after surgical intervention, were considered to be different clinical features from most reported cases. One patient was a compound heterozygote for p.Ser139Leu and p.Asp220Tyr, and the other for p.Ser139Leu and Glu160X. The mutations of the two alleles (p.Asp220Tyr and p.Glu160X) were novel and reports of p.Ser139Leu were rare both in Western and other Asian populations. These might suggest different genetic spectrum of Korean GA I patients