Chan-Hyung Kim

Epigallocatechin-3 gallate prevents cardiac hypertrophy induced by pressure overload in rats.

Pressure overload diseases, such as valvular stenosis and systemic hypertension, manifest morphologically in patients as cardiac concentric hypertrophy. Prevention of cardiac remodeling due to increased pressure overload is important to reduce morbidity and mortality. Epigallocatechin-3 gallate (EGCG) is a major bioactive polyphenol present in green tea which has been found to be a nitric oxide-mediated vasorelaxant and to be cardioprotective in myocardial ischemia-reperfusion injury. Therefore, we investigated whether EGCG supplementation could reduce in vivo pressure overload-mediated cardiac hypertrophy. Cardiac hypertrophy was induced by suprarenal transverse abdominal aortic constriction (AC) in rats. Three weeks after AC surgery, heart to body weight ratio increased in the AC group by 34% compared to the sham group. EGCG administration suppressed the load-induced increase in heart weight by 69%. Attenuation of cardiac hypertrophy by EGCG was associated with attenuation of the increase in myocyte cell size and fibrosis induced by aortic constriction. Despite abolition of hypertrophy by EGCG, transstenotic pressure gradients did not change. Echocardiogram revealed that increased left ventricular systolic dimensions and deteriorated systolic function were relieved by EGCG. These results suggest that EGCG prevents the development of left ventricular concentric hypertrophy by pressure overload and may be a useful therapeutic modality to prevent cardiac remodeling in patients with pressure overload myocardial diseases.

Local delivery of green tea catechins inhibits neointimal formation in the rat carotid artery injury model

It has been shown that green tea catechins (GTC) suppress proliferation of vascular smooth muscle cells (VSMCs) and that epigallocatechin-3-gallate (EGCG), which is a major constituent of GTC, selectively inhibits the platelet-derived growth factor-BB (PDGF-BB)-induced intracellular signaling transduction pathway. Vascular smooth muscle cell proliferation is one of major mechanisms of restenosis following percutaneous coronary intervention. This study tested whether GTC can inhibit VSMC proliferation and prevent neointimal formation in a rat carotid artery injury model. Vascular smooth muscle cell proliferation inhibition was analyzed with [3H]thymidine incorporation. Green tea catechins were applied to the endothelium-denuded carotid arteries of rats for 20 min. Angiography and morphometric analysis was performed after 2 weeks. Green tea catechins decreased [3H]thymidine incorporation stimulated with PDGF-BB dose dependently. In the absence of PDGF-BB, the decrement of [3H]thymidine incorporation was evident above a concentration of 10 µg/ml of GTC. Carotid arteriographic evaluation showed that the minimum luminal diameter in the GTC-treated group (n = 12) was 5.9 ± 1.6 arbitrary units (a.u.) and was significantly larger than in the control group (4.3 ± 1.4 a.u., n = 10) (P < 0.05). The GTC-treated group also showed a significant reduction in neointimal formation compared with the control group (0.29 ± 0.11 vs 0.42 ± 0.10 mm2, P < 0.05). To identify the active ingredients, we performed a similar experiment using EGCG. The effects of EGCG were similar to those of GTC. Green tea catechins effectively inhibited VSMC proliferation. Neointimal formation was prevented in the rat carotid artery injury model by local delivery of GTC. As EGCG showed similar effects, it may be one of the major constituents of GTC having these effects.

Mechanical Stretch-Induced Protection against Myocardial Ischemia-Reperfusion Injury Involves AMP-Activated Protein Kinase.

AMP-activated protein kinase (AMPK) protects various tissues and cells from ischemic insults and is activated by many stimuli including mechanical stretch. Therefore, this study investigated if the activation of AMPK is involved in stretch-induced cardioprotection (SIC). Intraventricular balloon and aorto-caval shunt (ACS) were used to stretch rat hearts ex vivo and in vivo, respectively. Stretch preconditioning reduced myocardial infarct induced by ischemia-reperfusion (I/R) and improved post-ischemic functional recovery. Phosphorylation of AMPK and its downstream substrate, acetyl-CoA carboxylase (ACC) were increased by mechanical stretch and ACC phosphorylation was completely blocked by the AMPK inhibitor, Compound C. AMPK activator (AICAR) mimicked SIC. Gadolinium, a blocker of stretch-activated ion channels (SACs), inhibited the stretch-induced phosphorylation of AMPK and ACC, whereas diltiazem, a specific L-type calcium channel blocker, did not affect AMPK activation. Furthermore, SIC was abrogated by Compound C and gadolinium. The in vivo stretch induced by ACS increased AMPK activation and reduced myocardial infarct. These findings indicate that stretch preconditioning can induce the cardioprotection against I/R injury, and activation of AMPK plays an important role in SIC, which might be mediated by SACs.

Combined bilateral anterior cingulotomy and ventral capsule/ventral striatum deep brain stimulation for refractory obsessive-compulsive disorder with major depression: Do combined procedures have a long-term benefit?

BACKGROUND The ventral capsule (VC), ventral striatum (VS), and the anterior cingulate gyrus are parts of the obsessive-compulsive disorder (OCD) and depression circuits. We assessed whether a combination of bilateral anterior cingulotomy and VC/VS deep brain stimulation (DBS) had an additive effect in patients with OCD and major depression. METHODS Three patients with refractory OCD underwent combined bilateral anterior cingulotomy and VC/VS DBS procedures. All patients met the inclusion criteria for the Korean guidelines of DBS for OCD. Baseline Yale-Brown Obsessive-Compulsive Disorder Scale (Y-BOCS) scores, Hamilton Depression Rating Scale scores, and global assessments of functioning were evaluated. These scores were also serially estimated for more than 24 months after surgery at 3-month intervals. RESULTS The mean value of the baseline Y-BOCS scores was 34.7 (range 30-38); the mean Y-BOCS value decreased significantly to 23.0 (range 20-25) 3 months after the surgery. This score was maintained 2 years after surgery with a mean value of 19.0 (range 18-20). CONCLUSIONS The combination of the two therapies did not yield superior outcomes, as the clinical outcomes were comparable to those of previous reports for VC/VS DBS alone. Wide-area VC/VS DBS may be sufficient to control refractory OCD.

Involvement of HIF-1α in UVB-induced epidermal hyperplasia

Keratinocyte overgrowth after UVB exposure is believed to contribute to skin photoageing and cancer development. However, little is known about the transcription factors that epigenetically regulate keratinocyte response to UVB. Recently, HIF-1α was found to play a role in epidermal homeostasis by controlling the keratinocyte cell cycle, and thus, we hypothesized that HIF-1α is involved in UVB-induced keratinocyte growth. In cultured keratinocytes, HIF-1α was found to be down-regulated shortly after UVB exposure and to be involved in UVB-induced proliferation. In mice repeatedly treated with UVB, the epidermis became hyperplasic and keratinocytes lacked HIF-1α in nuclei. Based on these results, we suggest that the deregulation of HIF-1α is associated with UVB-induced hyperplasia of the epidermis. This work provides insight of the molecular mechanism underlying UV-induced photoageing and skin cancer development.

Separation of magnesium isotopes by chemical exchange with a polymer-bound azacrown compound

The chromatographic separation of magnesium isotopes was investigated by chemical exchange with the recently synthesized 1-oxa-4,7,10,13-tetraazacyclopentadecane-4,7,10,13-tetramerrifield peptide resin [N4O·4M]. The capacity of the novel N4O-4 Merrifield ion exchanger was 1.0 meq/g dry resin. The heavier isotope26Mg concentrated in the resin phase, while the lighter isotopes24Mg, and25Mg are enriched in the fluid phase. The maximum separation factors α, for25Mg−26Mg and24Mg−26Mg were found to be 1.048 and 1.022, respectively, at 20.0±0.02 °C with 2.0 M ammonium chloride solution as an eluent.

Magnesium isotope separation by ion exchange using hydrous manganese(IV) oxide.

The magnesium isotope effects were investigated by chemical ion exchange with a hydrous manganese(IV) oxide. The capacity of manganese(IV) oxide was 0.5 meq g(-1). The distribution coefficient of magnesium ions on the MnO(2) was determined by a batch method. The heavier isotopes of magnesium were enriched in the solution phase, while the lighter isotopes were enriched in the hydrous MnO(2) phase. The separation factor was determined according to the method of Glueckauf from the elution curve and isotopic assays. The separation factors of (24)Mg(2+)-(25)Mg(2+), (24)Mg(2+)-(26)Mg(2+), and (25)Mg(2+)-(26)Mg(2+) isotope pair fractionations were 1.011, 1.021, and 1.011, respectively.

Enrichment of Magnesium Isotopes by N3O2 Azacrown Ion Exchange Resin

The elution chromatographic separation of magnesium isotopes was investigated by chemical ion exchange with the synthesized 1,7-dioxa-4,10,13-triazacyclopentadecane-4,10,13-trimerrifield peptide resin [N3O2·3M]. The capacity of novel N3O2 azacrown ion exchanger was 0.21 meq/g dry resin. The heavier isotopes of magnesium concentrated in the resin phase, while the lighter isotopes are enriched in the solution phase. The glass ion exchange column used in our experiment was 30 cm long with inner diameter of 0.2 cm, and the 2.0M NH4Cl solution was used as an eluent. The separation factors of 24Mg-25Mg, 25Mg-26Mg, and 24Mg-26Mg were 1.030, 1.009, and 1.027, respectively.

SEPARATION OF LITHIUM ISOTOPES WITH THE N3O2 TRIMERRIFIELD PEPTIDE RESIN

A study on the separation of lithium isotopes was carried out with 1,13-dioxa-4,7,10-triazacyclopentadecane-4,7,10-trimerrifield peptide resin [N3O23M]. The resin having N3O2 as an anchor group has a capacity of 0.2 meq/g dry resin. Upon column chromatography [0.1 cm (I.D)×30 cm (height)] using 1.0M NH4Cl solution as an eluent, a single separation factor of 1.00104 was obtained from the elution curve and isotope ratios based on theGlueckauf theory. The heavier isotope,7Li concentrated in the resin phase, while the lighter isotope,6Li enriched in the solution phase.

Separation of lithium isotopes by N4O2 azacrown ion exchanger

A study on the separation of lithium isotope was carried out with a 1,16-dioxa-4,7,10,13- tetraazacyclooctadecane-4,7,10,13-tetramerrifield peptide resin [N4O2·4M]. The resin having N4O2 as an anchor group has a capacity of 3.8 meq/g. Upon column chromatography [0.15 cm (I.D)×29 cm (height)] using 0.01 M NH4Cl as an eluent, the single separation factor, α=1.038 was obtained by the Glueckauf theory from the elution curve and isotope ratios.