June Hong Kim

Effects of surface treatments and lubricants for warm forging die life

Abstract In most metal forming applications, the surface treatments and lubricants are the main factors influencing die life, since they directly determine the interface friction and thermal insulation. In general, in hot and warm forging processes, the surface hardness of the die is decreased while the temperature of the die increased during repeated operations, which induce thermal softening. The thermal softening causes the plastic deformation of die despite the forming load not being changed. In this study, experiments and numerical analyses were performed under various conditions: two kinds of surface treatment, two lubricants, different initial billet temperatures and different loads; to investigate the effects on thermal softening and the amount of heat-transfer. Carbon nitride (CN x ), ion-nitride and no surface treatment for the dies were used and oil-based and water-based graphite were used as lubricants. Experiments were also performed to take the heat-transfer coefficient into account with the combination of surface treatments and lubricants. The coefficients determined were then used in a finite element model for the analysis of the backward extrusion process, the results produced were compared being experiment.

Incidence and predictors of drug-eluting stent fractures in long coronary disease

BACKGROUND Stent fractures after drug-eluting stent (DES) implantation have not been evaluated sufficiently in patients with long coronary artery disease. METHODS This study comprised of 415 patients, who were enrolled in the Long-DES-II study and had a complete serial angiography both before and after procedure and also at follow-up. The lesions were > or =25 mm in length and were randomly treated with sirolimus-eluting stents (SES, 210 lesions) or paclitaxel-eluting stent (205 lesions). RESULTS DES fracture was identified in 7 lesions (1.7%): 1 minor, 3 moderate, and 3 severe fractures. Most of the fractures occurred in patients who received SES (85.7%) and in the right coronary artery (RCA) lesions (71.4%). Lesions with fracture had a smaller minimal lumen diameter before procedure than lesions without fracture (0.38+/-0.55 vs. 0.71+/-0.46 mm, p=0.043). However, acute gain (2.28+/-0.39 vs. 1.44+/-0.60 mm, p=0.001) and late loss (0.81+/-0.49 vs. 0.42+/-0.50 mm, p=0.033) in analysis segment were greater in lesions with fracture. By multivariate analysis, the independent predictor of fracture was the RCA lesion (Odds ratio, 7.81; 95% CI, 1.45 approximately 42.04; p=0.017). Although one patient had an intermediate angiographic narrowing at the fracture site, there was no adverse cardiac event related with fracture. CONCLUSIONS The incidence of stent fracture in long DES implantation was not common and was associated with SES implantation or RCA lesions. Fortunately, the clinical prognosis of DES fracture was somewhat benign.

Culprit or multivessel revascularisation in ST-elevation myocardial infarction with cardiogenic shock

Objective The value of multivessel revascularisation in cardiogenic shock and multivessel disease (MVD) is still not clear. We compared outcomes following culprit vessel or multivessel revascularisation in patients with ST-elevation myocardial infarction (STEMI), cardiogenic shock and MVD. Methods From 16 620 patients with STEMI who underwent primary percutaneous coronary intervention (PCI) in a nationwide, prospective, multicentre registry between January 2006 and December 2012, 510 eligible patients were selected and divided into culprit vessel revascularisation (n=386, 75.7%) and multivessel revascularisation (n=124, 24.3%) groups. The primary outcomes were inhospital mortality and all-cause death during a median 194-day follow-up. A weighted Cox regression model was constructed to determine the HRs and 95% CIs for outcomes in the two groups. Results Compared with culprit vessel revascularisation, multivessel revascularisation had a significantly lower adjusted risk of inhospital mortality (9.3% vs 2.4%, HR 0.263, 95% CI 0.149 to 0.462, p<0.001) and all-cause death (13.1% vs 4.8%, HR 0.400, 95% CI 0.264 to 0.606, p<0.001), mainly because of fewer cardiac deaths (9.7% vs 4.8%, HR 0.510, 95% CI 0.329 to 0.790, p=0.002). In addition, multivessel revascularisation significantly decreased the adjusted risk of the composite endpoint of all-cause death, recurrent myocardial infarction and any revascularisation (20.3% vs 18.1%, HR 0.728, 95% CI 0.55 to 0.965, p=0.026). Conclusions This study showed that, compared with culprit vessel revascularisation, multivessel revascularisation at the time of primary PCI was associated with better outcomes in patients with STEMI with cardiogenic shock. Our results support the current guidelines regarding revascularisation in these patients.

MicroRNA-124 links p53 to the NF-κB pathway in B-cell lymphomas.

The contribution of microRNAs to lymphoma biology is not fully understood. In particular, it remains untested whether microRNA dysregulation could contribute to the emergence of the aggressive subset of B-cell lymphomas that coexpress MYC and BCL2. Here, we identify microRNA-124 (miR-124) as a negative regulator of MYC and BCL2 expression in B-cell lymphomas. Concordantly, stable or transient ectopic expression of miR-124 suppressed cell proliferation and survival, whereas genetic inhibition of this miRNA enhanced the fitness of these tumors. Mechanistically, the activities of miR-124 towards MYC and BCL2 intersect with both oncogenic and tumor-suppressive pathways. In respect to the former, we show that miR-124 directly targets nuclear factor-κB (NF-κB) p65, and using genetic approaches, we demonstrate that this interaction accounts for the miR-124-mediated suppression of MYC and BCL2. We also characterized miR-124 promoter region and identified a functional p53 binding site. In agreement with this finding, endogenous or ectopic expression of wild-type, but not mutant, p53 increased miR-124 levels and suppressed p65, MYC and BCL2. Our data unveil an miRNA-dependent regulatory circuitry that links p53 to the NF-κB pathway, which when disrupted in B-cell lymphoma may be associated with aberrant coexpression of MYC and BCL2 and poor prognosis.

Polyphenol (-)-Epigallocatechin Gallate during Ischemia Limits Infarct Size Via Mitochondrial KATP Channel Activation in Isolated Rat Hearts

Polyphenol (-)-epigallocatechin gallate (EGCG), the most abundant catechin of green tea, appears to attenuate myocardial ischemia/reperfusion injury. We investigated the involvement of ATP-sensitive potassium (KATP) channels in EGCG-induced cardioprotection. Isolated rat hearts were subjected to 30 min of regional ischemia and 2 hr of reperfusion. EGCG was perfused for 40 min, from 10 min before to the end of index ischemia. A nonselective KATP channel blocker glibenclamide (GLI) and a selective mitochondrial KATP (mKATP) channel blocker 5-hydroxydecanoate (HD) were perfused in EGCG-treated hearts. There were no differences in coronary flow and cardiodynamics including heart rate, left ventricular developed pressure, rate-pressure product, +dP/dtmax, and -dP/dtmin throughout the experiments among groups. EGCG-treatment significantly reduced myocardial infarction (14.5±2.5% in EGCG 1 µM and 4.0±1.7% in EGCG 10 µM, P<0.001 vs. control 27.2±1.4%). This anti-infarct effect was totally abrogated by 10 µM GLI (24.6±1.5%, P<0.001 vs. EGCG). Similarly, 100 µM HD also aborted the anti-infarct effect of EGCG (24.1±1.2%, P<0.001 vs. EGCG ). These data support a role for the KATP channels in EGCG-induced cardioprotection. The mKATP channels play a crucial role in the cardioprotection by EGCG.

Morphine-induced postconditioning modulates mitochondrial permeability transition pore opening via delta-1 opioid receptors activation in isolated rat hearts

Background It is generally accepted that morphine affords cardioprotection against ischemia/reperfusion injury. Inhibition of the mitochondrial permeability transition pore (MPTP) is considered an end target for cardioprotection. The aim of this study was to investigate the involvement of opioid receptors (OR) and MPTP in morphine-induced postconditioning (M-Post). Methods Isolated rat hearts were subjected to 30 min of regional ischemia and 2 h of reperfusion. Hearts were treated with 1 µM morphine, with or without the OR antagonists or a MPTP opener at early reperfusion. Infarct size was measured with 2,3,5-triphenyltetrazolium chloride staining. Results There were no significant differences in cardiodynamic variables except a decrease in heart rate in the M-Post group (P < 0.01 vs. control) after reperfusion. M-Post dramatically reduced infarct-risk volume ratio (9.8 ± 2.5%, P < 0.001 vs. 30.0 ± 3.7% in control). This beneficial effect on infarct volume by M-Post was comparable with ischemic postconditioning (11.9 ± 2.2%, P > 0.05). The nonspecific OR antagonist naloxone (25.7 ± 1.9%, P < 0.01), the δ-OR antagonist naltrindole (27.8 ± 4.3%, P < 0.05) and δ1-OR antagonist 7-benzylidenenaltrexone (24.7 ± 3.7%, P < 0.01) totally abrogated the anti-infarct effect of M-Post. In addition, the anti-infarct effect by M-Post was also totally blocked by the MPTP opener atractyloside (26.3 ± 5.2%, P < 0.05). Conclusions M-Post effectively reduces myocardial infarction. The anti-infarct effect by M-Post is mediated via activation of δ-OR, especially δ1-OR, and inhibition of the MPTP opening.

Comparison of 5 Different Remifentanil Strategies Against Myocardial Ischemia-Reperfusion Injury

OBJECTIVE The purpose of this study was to investigate the effects of various remifentanil strategies (preconditioning, postconditioning, or continuous infusion) against myocardial ischemia-reperfusion injury. DESIGN An in vitro experimental study using the Langendorff system. SETTING A university research laboratory. PARTICIPANTS Male Sprague-Dawley rats (each n = 9). INTERVENTIONS Five different remifentanil strategies were performed in isolated rat hearts as follows: remifentanil preconditioning (R-Pre), remifentanil postconditioning (R-Post), ischemic targeting remifentanil (R1), reperfusion targeting remifentanil (R2), or both ischemic and reperfusion targeting remifentanil (R3). Infarct size and cardiodynamics were compared. MEASUREMENT AND MAIN RESULTS The infarct-risk volume ratio in groups R-Pre (13.7% ± 9.9%), R-Post (13.7% ± 12.3%), and R3 (12.6% ± 6.1%) were decreased significantly compared with the untreated control hearts (32.9% ± 11.1%, p < 0.01). There was no significant difference in the left ventricular-developed pressure (LVDP) recovery after reperfusion between the control (43.6% ± 14.5%) and R-Pre (34.8% ± 12.9%, p > 0.05) groups after reperfusion. However, the LVDP recovery in R-Post (21.6% ± 7.7%, p < 0.05), R1 (16.7% ± 19.8%, p < 0.01), R2 (22.2% ± 13.9%, p < 0.05), and R3 (16.2% ± 7.8%, p < 0.01) was decreased significantly compared with control hearts. There was no significant difference in the recovery of dP/dt(max) after reperfusion between the R-Pre (42.0% ± 16.9%) and control groups (39.0% ± 15.4%, p > 0.05), whereas the dP/dt(max) in R3 group (16.9% ± 9.0%) was decreased significantly compared with R-Pre (p < 0.05). CONCLUSIONS Preconditioning or postconditioning by remifentanil and the continuous infusion of remifentanil effectively reduce myocardial infarction, whereas reperfusion targeting ischemic targeting or reperfusion targeting remifentanil does not. Remifentanil preconditioning better preserves myocardial function, especially LVDP, than other remifentanil strategies.

Adenosine-stress low-dose single-scan CT myocardial perfusion imaging using a 128-slice dual-source CT: a comparison with fractional flow reserve

Background Coronary CT angiography (CCTA) allows accurate evaluation of coronary artery stenosis but has limitations in information on hemodynamic significance of stenotic lesions. Purpose To determine the feasibility of adenosine-stress low-dose single-scan CT myocardial perfusion imaging (MPI) using a 128-slice dual-source CT scanner for the diagnosis of hemodynamically significant coronary artery stenosis as defined by fractional flow reserve (FFR). Material and Methods This study was proved by the Institutional Review Board and informed consent was obtained from the patients before enrollment in the study. Ninety-seven patients with chest pain and low-to-intermediate pretest probability of coronary artery disease were prospectively enrolled. Adenosine-stress CCTA using ECG-correlated maximum tube current modulation (Mindose®) with 128-slice dual-source CT was performed in all 97 patients. In 37 patients (38.1%; 28 men, nine women; mean age, 61.7 ± 20.5 years; mean heart rate, 74.6 ± 2.8 bpm) with significant stenosis at CCTA (lumen diameter reduction >50%), FFR was performed after CCTA, as a reference standard for the evaluation of myocardial perfusion. FFR value ≤0.75 was considered as positive. CTMPI and CCTA were read by two experienced radiologists with consensus, respectively. Results The effective radiation dose of adenosine-stress single-scan CTMPI was 4.63 ± 2.57 mSv. Compared with FFR, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for identifying significant coronary stenoses were 93.1%, 82.7%, 75.0%, and 95.6%, respectively, on CCTA and 93.1%, 90.3%, 84.4%, and 95.9%, respectively, on CTMPI. On combined CCTA and CTMPI, sensitivity, specificity, PPV, and NPV were 93.1%, 94.2%, 90.0%, and 96.0%, respectively. Conclusion Adenosine-stress low-dose single scan CTMPI using a 128-slice dual-source CT can provide complementary information on the hemodynamical significance of coronary artery stenosis as well as anatomical information of coronary arteries.

Gene expression signatures associated with the resistance to imatinib

Imatinib (imatinib mesylate, STI-571, Gleevec) is a selective BCR-ABL tyrosine kinase inhibitor that has been used as a highly effective chemoagent for treating chronic myelogenous leukemia. However, the initial response to imatinib is often followed by the recurrence of a resistant form of the disease, which is major obstacle to many therapeutic modalities. The aim of this study was to identify the gene expression signatures that confer resistance to imatinib. A series of four resistant K562 sublines was established with different imatinib dosage (200, 400, 600 and 800 nM) and analyzed using microarray technology. The transcripts of the genes showing universal or dose-dependent expression changes across the resistant sublines were identified. The gene sets associated with the imatinib-resistance were also identified using gene set enrichment analysis. In the resistant K562 sublines, the transcription- and apoptosis-related expression signatures were upregulated, whereas those related to the protein and energy metabolism were downregulated. Several genes identified in this study such as IGF1 and RAB11A have the potential to become surrogate markers useful in a clinical evaluation of imatinib-resistant patients without BCR-ABL mutation. The expression signatures identified in this study provide insights into the mechanism of imatinib-resistance and are expected to facilitate the development of an effective diagnostic and therapeutic strategy.

Step-and-shoot prospectively ECG-gated vs. retrospectively ECG-gated with tube current modulation coronary CT angiography using 128-slice MDCT patients with chest pain: diagnostic performance and radiation dose

Background With increasing awareness for radiation exposure, the study of diagnostic accuracy of coronary CT angiography (CCTA) with low radiation dose techniques is mandatory to both radiologist and clinician. Purpose To compare diagnostic performance and effective radiation dose between step-and-shoot prospectively ECG-gated and retrospectively ECG-gated with tube current modulation (TCM) CCTA using 128-slice multidetector computed tomography (MDCT). Material and Methods We retrospectively evaluated 60 patients who underwent CCTA with either of two different low-dose techniques using 128-slice MDCT (23 patients for step-and shoot-prospectively ECG-gated and 37 patients for retrospectively ECG-gated with TCM CCTA) followed by conventional coronary angiography. All coronary arteries and all segments thereof, except anatomical variants or small size (< 1.5 mm) ones, were included in analysis. Results In per-segment analysis, sensitivity, specificity, positive predictive value, and negative predictive value were 91/96%, 95/94%, 75/73%, and 98/99% for step-and-shoot prospectively ECG-gated and retrospectively ECG gated with TCM CCTA, respectively, relative to conventional coronary angiography. Effective radiation dose were 1.75 ± 0.83 mSv, 4.91 ± 1.71 mSv in the step-and-shoot prospectively ECG-gated and retrospectively ECG-gated with TCM CCTA groups, respectively. Conclusion The two low-radiation dose CCTA techniques using 128-slice MDCT yields comparable diagnostic performance for coronary artery disease in symptomatic patients with low heart rates.