Soo Wan Chae

Sulforaphane protects ischemic injury of hearts through antioxidant pathway and mitochondrial KATP channels

Reactive oxygen species are important mediators that exert a toxic effect during ischemia-reperfusion (I/R) injury of various organs. Sulforaphane is known to be an indirect antioxidant that acts by inducing Nrf2-dependent phase 2 enzymes. In this study, we investigated whether sulforaphane protects heart against I/R injury. Sprague-Dawley rats received sulforaphane (500microg/kg/day) or vehicle intraperitoneally for 3 days and global ischemia was performed using isolated perfused Langendorff hearts. Hearts were perfused with Krebs-bicarbonate buffer for 20min pre-ischemic period followed by a 20min global ischemia and 50min reperfusion. Treatment with sulforaphane inhibited an increase in the post-ischemic left ventricular end-diastolic pressure (LVEDP) and improved the post-ischemic left ventricular developed pressure (LVDP), +/-dP/dt, and coronary flow as compared with the untreated control hearts. Pretreatment with 5-hydroxydecanoic acid (5-HD), a mitochondrial K(ATP) channel blocker, for 10min before ischemia attenuated the improvement of LVEDP, LVDP, +/-dP/dt, and coronary flow induced by sulforaphane. Sulforaphane markedly decreased the infarcted size and attenuated the increased lactate dehydrogenase level in effluent during reperfusion. Pretreatment with 5-HD also blocked these protective effects of sulforaphane. Post-ischemia increased the concentration of atrial natriuretic peptide in coronary effluent, which attenuated by sulforaphane treatment. Decreases on Mn-superoxide dismutase (SOD), catalase, and heme oxygenase-1 levels by I/R were increased by sulforaphane treatment and pretreatment of 5-HD blocked the sulforaphane effects. Increases in Bax and caspase-3 levels, and decrease in Bcl-2 level by I/R were attenuated by sulforaphane treatment. These results suggest that the protective effects of sulforaphane against I/R injury may be partly mediated through mitochondrial K(ATP) channels and antioxidant pathway.

Glibenclamide suppresses stretch-activated ANP secretion: involvements of K+ATP channels and L-type Ca2+ channel modulation

Abstract The mechanism by which glibenclamide regulates mechanically activated atrial natriuretic peptide (ANP) secretion was investigated using isolated perfused rat atria. A reduction in atrial pressure from an experimentally imposed distending pressure stimulated the secretion of ANP and caused concomitant translocation of extracellular fluid (ECF) into the atrial lumen. The activation of ANP secretion and ECF translocation were closely correlated with atrial volume changes and the increase in ANP secretion was a function of the ECF translocation. Glibenclamide (1, 10, 100 μM), an ATP-sensitive K+ (K+ATP) channel blocker, had no effect on the basal secretion of ANP, suppressed the stimulation of stretch-activated ANP secretion in a dose-dependent manner, but not the translocation of the ECF. Glipizide (100 μM) and tolbutamide (100 μM), other K+ATP channel blockers, had similar effects to those of glibenclamide. Suppression by glibenclamide (100 μM) of the stretch-induced ANP secretion was not observed in atria that had been pretreated with pinacidil (200 μM), an ATP-sensitive K+ channel opener: pinacidil alone had no effect on ECF translocation and ANP secretion. Furthermore, blocking Ca2+ influx by using the Ca2+ channel blocker diltiazem (10 nM), or a Ca2+-depleted medium prevented the suppression of stretch-induced ANP secretion by glibenclamide. In other experiments, atrial distension produced a slight membrane depolarization of cardiomyocytes; this was accentuated in the presence of glibenclamide. Furthermore, in single cardiomyocytes, glibenclamide increased the intracellular Ca2+ concentration ([Ca2+]i) in a dose-dependent manner. From these results, we suggest that glibenclamide suppresses atrial release of ANP by blocking K+ATP channels and increasing Ca2+ influx and that the K+ATP channels are associated with the regulation of the mechanically activated ANP secretion from the atria.

Dexamethasone Suppresses Tumor Necrosis Factor-α-Induced Apoptosis in Osteoblasts: Possible Role for Ceramide1

Ceramide has been proposed as a second messenger molecule implicated in a variety of biological processes, including apoptosis. Recently, it has been reported that tumor necrosis factor-α (TNF-α) activates the release of ceramide and that ceramide acts as a mediator for the TNF-α-induced stimulation of the binding affinity of nuclear factor-κB (NF-κB), a ubiquitous transcription factor of particular importance in immune and inflammatory responses. In this study we demonstrate that dexamethasone, which reduces the production of ceramide, significantly inhibits TNF-α-induced activation of NF-κB, c-Jun N-terminal kinase, also known as stress-activating protein kinase, caspase-3-like cysteine protease, redistribution of cytochrome c, and apoptosis in MC3T3E1 osteoblasts. Compared with TNF-α-induced JNK activation, ceramide elicits a more rapid activation of JNK within 30 min. C2-ceramide activates NF-κB and caspase-3 like protease to the same degree and with kinetics similar to those of TNF-α. This study prov...

Reciprocal modulation of ATP-sensitive K+ channel activity in rat ventricular myocytes by phosphorylation of tyrosine and serine/threonine residues.

The modulation of ATP-sensitive K+ channel (KATP) activity by specific phosphorylation or dephosphorylation of tyrosine and serine/threonine residues was examined in rat ventricular myocytes using the inside-out patch configuration of the patch clamp technique. The run-down process was suppressed by okadaic acid but accelerated by sodium orthovanadate. After run-down of the channels, the ATP-induced reactivation was blocked by H-7, but enhanced by genistein. The channel activity was decreased by protein phosphatase 2A. However, the activity of partially run-down channels was increased by protein tyrosine phosphatase 1B. Our results suggest that KATP channel activity can be inhibited by phosphorylation of tyrosine residues and stimulated by phosphorylation of serine/threonine residues.

Kochujang, fermented soybean-based red pepper paste, decreases visceral fat and improves blood lipid profiles in overweight adults

Health benefits of Kochujang (KCJ) and its bioactive compounds have been reported in several in vitro and animal studies.ObjectiveThe aim of this study was to investigate the efficacy of KCJ supplementation on body composition and blood lipid profiles in overweight adults.MethodsSixty overweight men and women with BMI ≥23 kg/m2 and waist-hip-ratio (WHR) ≥0.90 for men and ≥0.85 for women were randomly assigned to a KCJ supplement (n=30, 32 g/day) or placebo (n=30, 32 g/day) group for a 12-week, double-blind, placebo controlled study. We measured anthropometric parameters, serum lipid profiles, abdominal fat distribution by computerized tomography and calculated the atherosclerosis indices in 53 subjects (n=26 in KCJ group, n=27 in placebo group) who completed the study.ResultsAfter 12 weeks, the KCJ group showed a significant reduction in visceral fat (cm2) (p<0.05), although body weight (kg) and WHR did not change. Serum concentration of triglycerides and ApoB were decreased when compared to those of the placebo group.ConclusionKCJ supplementation (32 g/day) for 12 weeks in overweight adults showed anti-atherosclerotic and anti-obesogenic effects.Trial registrationClinical trials.gov Identifier:NCT01532375

Liquid chromatography-electrospray lonization tandem mass spectrometric determination of lornoxicam in human plasma

A rapid, sensitive and selective liquid chromatography-electrospray ionization tandem mass spectrometric (LC-ESI-MS/MS) method for the determination of lornoxicam in human plasma was developed. Lornoxicam and isoxicam (internal standard) were extracted from human plasma with ethyl acetate at acidic pH and analyzed on a Sunfire C18 column with the mobile phase of methanol:ammonium formate (10 mM, pH 3.0) (70:30, v/v). The analyte was detected using a mass spectrometer, equipped with electrospray ion source. The instrument was set in the multiple-reaction-monitoring mode. The standard curve was linear (r = 0.9998) over the concentration range of 0.50-500 ng/mL. The coefficient of variation and relative error for intra-and inter-assay at four QC levels were 0.7 to 4.2% and -4.5 to 5.0%, respectively. The recoveries of lornoxicam and isoxicam were 87.8% and 66.5%, respectively. The lower limit of quantification for lornoxicam was 0.50 ng/mL using a 200 μL plasma sample. This method was successfully applied to a pharmacokinetic study of lornoxicam after oral administration of lornoxicam (8 mg) to humans.

Visceral fat and body weight are reduced in overweight adults by the supplementation of Doenjang, a fermented soybean paste

Various forms of fermented soybean products are well documented for their health benefits. The efficacy of anti-obesogenic effect of Doenjang, one of the most commonly used seasonings in Korean cuisine, has been reported only in animal models; thus, an evaluation of Doenjang needs to be conducted in human studies. We aimed to test the hypothesis that Doenjang supplementation reduces body weight and changes body composition in overweight adults. A total of 51 overweight adults participated in this study. A group of males with BMI ≥ 23 kg/m2 and waist to hip ratio (WHR) ≥ 0.90, and a group of females with BMI ≥ 23 kg/m2 and WHR ≥ 0.85 were randomly assigned to either a Doenjang supplement (9.9 g dry/day) group or a placebo group for a 12-week randomized, double-blind and placebo-controlled study. Anthropometric parameters, abdominal fat distribution by computerized tomography (CT) and blood components were measured before and after the intervention period. After the 12-week study, the Doenjang supplementation group had significant reductions in body weight (kg), body fat mass (kg) and body fat (%) compared to the placebo group, the supplementation of Doenjang resulted in a significant reduction in visceral fat (cm2), although no changes were observed in total and subcutaneous fat are as (cm2), serum lipid profiles and dietary intakes. The present study demonstrated that daily supplementation of 9.9 g dry/day of Doenjang for 12 weeks reduces body weight and visceral fat in overweight adults.

Effects of male silkworm pupa powder on the erectile dysfunction by chronic ethanol consumption in rats

Erectile dysfunction (ED) is a highly prevalent disorder that affects millions of men worldwide. ED is now considered an early manifestation of atherosclerosis, and consequently, a precursor of systemic vascular disease. This study was designed to investigate the effects of male silkworm pupa powder (SWP) on the levels of nitric oxide synthase (NOS) expression, nitrite, and glutathione (GSH); lipid peroxidation; libido; and erectile response of the corpus cavernosum of the rat penis. We induced ED in the study animals by oral administration of 20% ethanol over 8 weeks. The SWP-treated male rats were divided into 3 groups that were orally administered 200, 400, and 800 mg/kg. The libido of the SWP-administered male rats was higher than that of the ethanol control group. In addition, the erectile response of the corpus cavernosum was restored in males on SWP administration, to a level similar to that of the normal group without ED. The testosterone concentration did not increase significantly. The lipid peroxidation in the corpus cavernosum of the male rats administered SWP decreased significantly. In contrast, compared to the ethanol group, SWP-administered male rats showed increased GSH levels in the corpus cavernosum. The level of nitrite and NOS expression in the corpus cavernosum of SWP-administered male rats increased significantly. These results indicated that SWP effectively restored ethanol-induced ED in male rats.

The Correlation and Accuracy of Glucose Levels between Interstitial Fluid and Venous Plasma by Continuous Glucose Monitoring System

Background Clinical experience with the continuous glucose monitoring systems (CGMS) is limited in Korea. The objective of this study is to evaluate the accuracy of the CGMS and the correlation between interstitial fluid and venous plasma glucose level in Korean healthy male subjects. Methods Thirty-two subjects were served with glucose solution contained same amount of test foods carbohydrate and test foods after separate overnight fasts. CGMS was performed over 3 days during hopitalization for each subjects. Venous plasma glucose measurements were carried out during 4 hours (0, 0.25, 0.5, 0.75, 1, 2, 4 hours) just before and after glucose solution and test food load. The performance of the CGMS was evaluated by comparing its readings to those obtained at the same time by the hexokinase method using the auto biochemistry machine (Hitachi 7600-110). Also, correlations between glucose recorded with CGMS and venous plasma glucose value were examined. Results CGMS slightly underestimated the glucose value as compared with the venous plasma glucose level (16.3 ± 22.2 mg/dL). Correlation between CGMS and venous plasma glucose values throughout sensor lifetime is 0.73 (regression analysis: slope = 1.08, intercept = 8.38 mg/dL). Sensor sensitivity can deteriorate over time, with correlations between venous blood glucose and CGMS values dropping from 0.77 during 1st day to 0.65 during 2nd and 3rd day. Conclusion The accuracy of data provided by CGMS may be less than expected. CGMS sensor sensitivity is decreased with the passage of time. But, from this study, CGMS can be used for glucose variability tendency monitoring conveniently to the Korean.

Improved cognitive performance following supplementation with a mixed-grain diet in high school students: a randomized controlled trial.

OBJECTIVE Adolescence is a stage of rapid growth, when rich nutritional supplementation is important. Maintaining optimal cognitive functioning is critical in high school students, who are under considerable academic pressure. The objectives of this study were to identify the effects of a 9-wk randomly assigned diet of mixed grains versus a regular diet on cognitive performance and on levels of plasma brain-derived neurotrophic factor (BDNF) and S100B, a calcium-binding protein produced by astroglial cells, in healthy high school students (grades 10 and 11). METHODS In this 9-wk, single-blind, controlled study, subjects were randomly allocated to either a mixed-grain or a regular diet. Cognitive assessments and measurements of plasma BDNF and S100B levels were performed at baseline and after the 9-wk intake of a mixed-grain or regular diet. Computerized neuropsychological tests and self-rating scales were used for the cognitive assessments. RESULTS Significant improvements in some neuropsychological tests were found after 9 wk in both the mixed-grain and the regular-diet groups, but the changes from baseline between the two groups were not significantly different. Significant impairments on the AX-continuous performance test were observed at the endpoint in the regular-diet group, and the changes from baseline between the two groups were also significantly different for this test. A significant difference in changes in BDNF levels was observed between the two groups. CONCLUSIONS These results suggest that intake of mixed grains for 9 wk is beneficial for cognitive performance and plasma BDNF levels in high school students. These beneficial effects seem to be related to the prevention of cognitive deterioration in a mental-fatigue test with the mixed-grain diet, rather than cognitive enhancement per se.