Tollip suppresses MyD88-mediated NF-κB activation by enhancing MyD88 ubiquitination levels in large yellow croaker (Larimichthys crocea).

Toll-interacting protein (Tollip) plays an important role in the innate immune response by negative regulation of the TLR-IL-1R signaling pathway. MyD88 serves as a universal adaptor in TLR-mediated NF-κB activation. However, the regulation mechanisms of Tollip in piscine MyD88-mediated NF-κB activation is largely unknown. In the present study, the cDNA sequence of LcTollip was identified from the large yellow croaker (Larimichthys crocea). The putative LcTollip protein encoded 275 amino acid residues, containing a N-terminal TBD domain, a central C2 domain, and a C-terminal CUE domain. Quantitative PCR showed that the most predominant constitutive expression of LcTollip was detected in spleen. In addition, LcTollip transcripts enhanced significantly after LPS and poly I:C challenge (P < 0.05). Cellular localization revealed that LcTollip existed in the cytoplasm and nucleus. Furthermore, the overexpression plasmids of wild type LcTollip as well as its six domain truncated mutants of LcTollip were constructed by overlap PCR. Dual luciferase analysis showed that NF-κB activation could not be induced by overexpression of LcTollip or its domain truncated mutants alone. However, the LcMyD88-induced-NF-κB activation was significantly suppressed by overexpression with LcTollip, and the truncated mutants LcTollip-ΔTBD, LcTollip-ΔC2, LcTollip-ΔCUE and LcTollip-ΔTBDΔCUE while not by LcTollip-ΔLR and LcTollip-ΔTBDΔC2. Moreover, co-immunoprecipitation (Co-IP) assay revealed that the interaction between LcTollip and LcMyD88 was through CUE domain. More interesting, IP and immunoblotting examination of HEK293T cells co-transfected with LcMyD88, LcTollip and HA-ubiquitin showed that LcMyD88 induced a dose-dependent de-ubiquitination of LcTollip while LcTollip enhanced a dose-dependent ubiquitination of LcMyD88. However, protein degradation investigation displayed that the proteolysis and ubiquitination of LcMyD88 were not connected. Our findings suggested that the LcTollip might involve in negative regulation TLR pathway by suppressing LcMyD88-mediated immune activation and improving the ubiquitination level of LcMyD88.

[Expression of ß-catenin in Skin Lesions of Patients with Scleroderma and Its Effect on Epithelial-Mesenchymal Transition of Human Epidermal Keratinocytes].

OBJECTIVE: To investigate the expression of ß-catenin in the skin lesions of patients with systemic scleroderma (SSc) and its effect on epithelial-mesenchymal transition (EMT) of human epidermal keratinocytes. METHODS: The expression of ß-catenin, Snail1 and E-cadherin in the skin lesions sample of 45 SSc patients and normal skin sample from 20 healthy adults was detected with SP immunohistochemistry. HaCaT, the human epidermal keratinocytes, were treated with different concentrations of Wnt10b (0 ng/mL (control), 2 ng/mL and 4 ng/mL) for 48 h. then detected the localization of ß-catenin in HaCaT cells by immunofluorescence assay, determined the mRNA levels of Snail1 and Snail2 in HaCaT cells by real-time fluorescent quantitative PCR, detected the proteins expression of ß-catenin, Vimentin, N-cadherin and E-cadherin in HaCaT cells by Western blot. RESULTS: The positive rates of ß-catenin, Snail1 and E-cadherin in skin lesions of SSc patients were 100%, 88.89% and 2.22% respectively, while in healthy adult skin, the corresponding positive rates were 0%, 10.00%, and 95.00%. The difference between the two groups was significant. Compared with control group, treatment with different concentrations of Wnt10b (2 ng/mL and 4 ng/mL) induced up-regulation of ß-catenin expression and promoted translocation of ß-catenin from cytoplasm to nucleus, increased the mRNA levels of Snail1 and Snail2 (P < 0.05), and up-regulated the proteins expression of Vimentin, N-cadherin, down-regulated the E-cadherin protein expression in HaCaT cells (P < 0.05). CONCLUSIONS: Abnormally activated Wnt/ß-catenin signaling pathway and abnormally expressed EMT-related proteins are observed in SSc lesions. Activation of Wnt/ß-catenin signaling pathway may promote EMT in HaCaT cells.

Impact of old age on clinical and angiographic characteristics of coronary artery spasm as assessed by acetylcholine provocation test.

BACKGROUND: Smoking and other risk factors have been well known as important factors of variant angina or coronary artery spasm (CAS). However, clinical features related to age on coronary artery spasm have been rarely evaluated. METHODS: We evaluated 3155 consecutive patients with insignificant coronary artery lesion. Patients underwent Acetylcholine (Ach) provocation test for induction of CAS. CAS was defined as > 70% luminal narrowing of coronary arteries during Ach provocation test. The results of Ach provocation test were compared among age groups; < 45 years (Group 1), 45-54 years (Group 2), 55-64 years (Group 3), and ≥ 65 years (Group 4). RESULTS: Older patients had higher incidence of hypertension, diabetes, but lower incidence rate of current smoking, male sex compared with younger patients. Positive Ach provocation test finding was frequently showed with aging (47.36% vs. 58.3% vs. 62.6% vs. 61.5%; P < 0.001). Multivariate logistic analysis showed that age, male, and myocardial bridge were independent predictors of CAS induced by Ach provocation test. CONCLUSION: Our present study showed that old age was independent predictor for Ach-induced significant coronary artery spasm.

[Effects of Compound Aconitum Polysaccharide on Glycosylation of Tumor Cells].

Objective To observe inducing or inhibiting effects of Chinese medicine (CM) poly- saccharides on glycoprotein chain synthetized different glycosyltransferases, thus disclosing targets of CM polysaccharides and its mechanisms. Methods In vivo anti-tumor effects of CM polysaccharides were observed using the inhibiting rate of tumor growth by dividing different Aconitum containing groups. Effects of CM polysaccharides on liver cancer cell SK-HEP-1 glycosyltransferase and tumor related gene expressions were observed. Meanwhile, changes of polylactosamine expression were detected using flow cytometry (FCM) with polylactosamine specific biotin labeling lectin. Results Compared with the model group, the average tumor weight was significantly lower in each medication group (P <0. 01). Compared with the adriamycin group, no significant difference in average tumor weight of the three compound groups (P>0. 05). The expression level of polylactosamine was reduced after adding Aconitum polysac- charide; and CM compound polysaccharides respectively. Conclusions Polysaccharide compound showed similar anti-tumor effect as that of adriamycin. Besides, polylactosamine expression level was reduced in the three compound groups along with increased prepared Aconitum polysaccharide, with more obvious anti-tumor effects shown.

Comparisons of everolimus and Paclitaxel-eluting stents in patients with acute myocardial infarction.

BACKGROUND: It has been established that the newer-generation drug-eluting stent (DES) everolimus-eluting stent (EES) is superior to the first-generation DES paclitaxel-eluting stent (PES). However, the advantages of EES over PES in the setting of acute myocardial infarction (AMI) need to be fully elucidated. METHODS: The present analysis enrolled 2,911 AMI patients receiving PES (n = 1,210) or EES (n = 1,701) in a large-scale, prospective, multicenter Korea Acute Myocardial Infarction Registry (KAMIR). Propensity score matching was used to adjust for baseline biases in clinical and angiographic characteristics, yielding a total of 2,398 patients (1,199 receiving PES and 1,199 receiving EES). Various clinical outcomes at 1 year were compared between the two propensity score matched groups. Target lesion failure (TLF) was defined as the composite of cardiac death, recurrent nonfatal myocardial infarction (Re-MI), or target lesion revascularization (TLR). RESULTS: Baseline clinical and angiographic characteristics were comparable between the two groups after propensity score matching. Clinical outcomes of the propensity score matched patients showed that the rates of in-hospital and 1-year cardiac and all-cause death were similar between the two groups. But patients in the EES group had significantly lower incidences of Re-MI (1.4% vs 2.8%, P = 0.002), TLR (1.2% vs 3.1%, P = 0.001), TLF (6.4% vs 10.2%, P = 0.001), and probable or definite stent thrombosis (0.3% vs 1.8%, P < 0.001) than did those in the PES group. CONCLUSIONS: The present propensity matched analysis suggests that the use of EES in the setting of AMI appears to be superior to PES in reducing TLF, and stent thrombosis.

Role of red blood cell distribution in predicting drug-eluting stent restenosis in patients with stable angina pectoris after coronary stenting.

BACKGROUND: It has been reported that increased red blood cell distribution width (RDW) predicts adverse events in cardiovascular disease and in patients undergoing percutaneous coronary intervention. However, the role of serum RDW levels in drug-eluting stent (DES) restenosis remains unclear. We aimed to investigate the relationship between serum RDW levels and in-stent restenosis (ISR) after coronary stenting with DES in stable angina pectoris (SAP) patients. MATERIALS AND METHODS: A total of 293 consecutive chronic SAP patients with coronary DES implantation were enrolled in this study. The ISR was analyzed by coronary angiography analysis at a mean follow-up of 8 months. According to whether ISR was detected, patients were divided into two groups: the ISR group (n=45) and the non-ISR group (n=247). Serum RDW was assessed both at admission and at the 8-month follow-up in all patients. Standard medication was continued throughout the investigation period. RESULTS: Baseline characteristics of the two groups were similar. Patients in the ISR group had significantly higher RDW levels compared with patients in the non-ISR group both at admission and at follow-up (P<0.01, respectively). Furthermore, the ISR group had significantly longer stent length and lower stent diameter compared with the non-ISR group (P<0.01, respectively). In a multivariate analysis, diabetes mellitus, current smoking, RDW levels, C-reactive protein levels, stent length, and stent diameter were associated independently with ISR. CONCLUSION: Serum RDW level may independently predict ISR at both admission and follow-up in SAP patients with coronary DES implantation, which indicates that a chronic inflammatory response might be involved in the pathogenesis of ISR.

One-year clinical outcomes of everolimus- versus sirolimus-eluting stents in patients with acute myocardial infarction.

BACKGROUND: In contrast to many studies comparing everolimus-eluting stent (EES) with paclitaxel-eluting stent (PES), data directly comparing EES with sirolimus-eluting stent (SES) are limited, especially in patients with acute myocardial infarction (AMI). METHODS: This study includes 2911 AMI patients treated with SES (n=1264) or EES (n=1701) in Korea Acute Myocardial Infarction Registry (KAMIR). Propensity score matching was applied to adjust for baseline imbalance in clinical and angiographic characteristics, yielding a total of 2400 well-matched patients (1200 receiving SES and 1200 receiving EES). One-year clinical outcomes were compared between the two propensity score matched groups. RESULTS: Baseline clinical and angiographic characteristics were similar between the two propensity score matched groups. One-year clinical outcomes of the propensity score matched cohort were comparable between the EES versus the SES groups including the rates of cardiac death (4.8% vs. 4.8%, P=1.000), recurrent myocardial infarction (1.4% vs. 1.7%, P=0.619), target lesion revascularization (1.4% vs. 1.6%, P=0.737), target lesion failure (7.0% vs. 7.3%, P=0.752), and probable or definite stent thrombosis (0.5% vs. 0.9%, P=0.224) except for a trend toward lower incidence of target vessel revascularization (1.9% vs. 3.0%, P=0.087) and a lower rate of total major adverse cardiac events (9.3% vs. 11.9%, P=0.034) in the EES group. CONCLUSIONS: The present propensity score matched analysis performed in a large-scale, prospective, multicenter registry suggests that the second-generation drug-eluting stent EES has at least comparable or even better safety and efficacy profiles as compared with SES in the setting of AMI.

Diabetes mellitus is not a risk factor for coronary artery spasm as assessed by an intracoronary acetylcholine provocation test: angiographic and clinical characteristics of 986 patients.

OBJECTIVES: Both diabetes mellitus (DM) and coronary artery spasm (CAS) are associated with endothelial dysfunction. Thus, a higher incidence of CAS is expected in diabetic patients (pts). We evaluated the impacts of DM and the status of blood sugar control on CAS with intracoronary acetylcholine (ACh) provocation test. METHODS: A total of 986 pts (106 DM vs 880 non-DM pts) with angiographically normal coronary artery received ACh provocation test. Significant CAS was defined as a transient >90% luminal narrowing with concurrent chest pain and/ or ST-segment changes. HbA1c <7% was considered a controlled blood sugar level. RESULTS: The incidence of CAS was similar between patients with versus without DM (30.2% vs 23.5%; P=.13). Multivariable analysis showed that DM was not an independent risk factor for significant CAS (odds ratio [OR], 1.29; 95% confidence interval [CI], 0.81-2.07; P=.28). The angiographic characteristics of CAS were also similar between these two groups. Subgroup analysis regarding the impact of the status of blood sugar control on CAS showed that the incidence of CAS was similar between diabetic pts with versus without controlled blood sugar levels (35.4% vs 25.9%; P=.29). Multivariable analysis showed that the uncontrolled blood sugar level was not an independent risk factor for CAS (OR, 0.79; 95% CI, 0.29-2.13; P=.64). CONCLUSIONS: Despite the expected endothelial dysfunction, DM and the status of blood sugar control are not associated with CAS, suggesting the existence of different mechanisms for CAS and coronary artery disease.

Efficacy of short-term cordyceps sinensis for prevention of contrast-induced nephropathy in patients with acute coronary syndrome undergoing elective percutaneous coronary intervention.

Contrast-induced nephropathy (CIN) is one of the major causes of hospital-acquired acute renal failure. The pathophysiological mechanism of CIN remains unknown. There has been little evidence regarding the effects of Traditional Chinese Medicine (TCM) on CIN. Cordyceps sinensis (CS), a traditional Chinese herb, has been widely used clinically for the prevention of the progression of renal failure. We performed a prospective, randomized controlled trial to investigate the role of CS in the prevention of CIN in patients with acute coronary syndrome (ACS) undergoing elective percutaneous coronary intervention (PCI). The 150 ACS patients were randomly assigned to three groups, basic treatment group (n=51), standard CS therapy group (n=49, corbrin capsule 2 g, 3 times/d were used 3 days before and after angiography), and intensive CS therapy group (n=50, corbrin capsule 3 g, 3 times/d were used 3 days before and after angiography). Renal function was assessed at the time of hospital admission and on days 1, 2, and 3 after PCI. CIN occurred in 13 of 150 patients (8.67%). The incidence of CIN was lower in the CS treatment groups than in the basic treatment group (P<0.05), and a significant decrease in the incidence of CIN in the intensive CS therapy group was shown (P<0.01). In conclusion, prophylactic treatment with CS during the peri-procedural stage in ACS patients undergoing elective PCI has a preventive role against CIN, and intensive CS therapy could be more effective.

The impact of high sensitivity C-reactive protein level on coronary artery spasm as assessed by intracoronary acetylcholine provocation test.

PURPOSE: High sensitive C-reactive protein (hs CRP) is well known as a strong risk factor of cardiovascular disease (CVD). The aim of this study is to evaluate the impact of elevated hs CRP on coronary artery spasm (CAS) as assessed by intracoronary acetylcholine (ACh) provocation test. MATERIALS AND METHODS: A total of 1729 consecutive patients without significant CVD who underwent coronary angiography and intracoronary ACh test between November 2004 and August 2010 were analyzed. The patients were divided into five groups according to quintiles of hs CRP levels. RESULTS: At baseline, the prevalence of elderly, hypertension, diabetes mellitus, current smoking, and lipid levels were higher in patients with higher hs CRP. During ACh test, the incidences of significant CAS, ischemic electrocardiography (EKG) change, multivessel, and diffuse CAS were higher in patients with higher hs CRP. Multivariate analysis showed that the old age (OR=1.01, CI; 1.0-1.02, p=0.0226), myocardial bridge (OR=3.34, CI; 2.16-5.17, p<0.001), and highest quintile hs CRP (OR=1.54, CI; 1.12-2.18, p=0.008) were independent predictors of ACh induced CAS. However, there was no difference in clinical outcomes up to 12 months. CONCLUSION: In conclusion, higher hs CRP was associated with higher incidence of CAS, worse angiographic characteristics and ischemic EKG change, but was not associated with clinical outcomes.

Six-month angiographic and one-year clinical outcomes of polymer free paclitaxel-eluting stent in patients with ST-segment elevation myocardial infarction: a comparison with permanent polymer sirolimus-eluting stent.

BACKGROUND: Since permanent polymer is implicated in adverse events associated with delayed vessel healing after drug eluting stents (DES) implantation, great efforts have been made to develop more biocompatible DES with biodegradable polymer or without polymer. The present study aimed to evaluate the safety and efficacy of polymer free paclitaxel-eluting stents (PF-PES) in comparison with permanent polymer sirolimus-eluting stents (PP-SES) in patients with acute ST-segment elevation myocardial infarction (STEMI). METHODS: Patients with STEMI were randomly assigned to receive PP-SES (n = 55), and PF-PES (n = 50). The 6-month angiographic and 1-year clinical outcomes were compared between the two groups. Target lesion failure (TLF) was defined as the composite of cardiac death, recurrent nonfatal myocardial infarction (Re-MI), or target lesion revascularization (TLR). RESULTS: Follow-up angiography at six months was performed in 72.7% of the PP-SES group and 70.0% of the PF-PES group (P = 0.757). The two groups had comparable angiographic outcomes including minimal luminal diameter, diameter stenosis, late loss and binary restenosis. All patients were clinically followed up to one year. The two groups had similar clinical outcomes with relatively low rates of target lesion failure (10.9% PP-SES vs. 12.0% PF-PES, P = 0.861) and definite or probable stent thrombosis (1.8% PP-SES vs. 2.0% PF-PES, P = 1.000) at one year. CONCLUSIONS: The present study suggests that the safety and efficacy of PF-PES in the setting of STEMI are comparable to PP-SES. Further randomized trials with larger study populations are needed to get definite conclusions.

Unrestricted use of 2 new-generation drug-eluting stents in patients with acute myocardial infarction: a propensity score-matched analysis.

OBJECTIVES: This study sought to compare everolimus-eluting stents (EES) with zotarolimus-eluting stents (ZES) in patients with acute myocardial infarction (AMI). BACKGROUND: There is a paucity of data to exclusively evaluate the safety and efficacy of second-generation drug-eluting stents (DES) in the setting of AMI. METHODS: The present study enrolled 3,309 AMI patients treated with ZES (n = 1,608) or EES (n = 1,701) in a large-scale, prospective, multicenter registry-KAMIR (Korea Acute Myocardial Infarction Registry). Propensity score matching was applied to adjust for differences in baseline clinical and angiographic characteristics, producing a total of 2,646 patients (1,343 receiving ZES, and 1,343 receiving EES). Target lesion failure (TLF) was defined as the composite of cardiac death, recurrent nonfatal myocardial infarction, or target lesion revascularization. Major clinical outcomes at 1 year were compared between the 2 propensity score-matched groups. RESULTS: After propensity score matching, baseline clinical and angiographic characteristics were similar between the 2 groups. Clinical outcomes of the propensity score-matched patients showed that, despite similar incidences of recurrent nonfatal myocardial infarction and in-hospital and 1-year mortality, patients in the EES group had significantly lower rates of TLF (6.5% vs. 8.7%, p = 0.029) and probable or definite stent thrombosis (0.3% vs. 1.6%, p < 0.001), compared with those in the ZES group. Furthermore, there was a numerically lower rate of target lesion revascularization (1.2% vs. 2.2%, p = 0.051) in the EES group than in the ZES group. CONCLUSIONS: In this propensity-matched comparison, EES seems to be superior to ZES in reducing TLF and stent thrombosis in patients with AMI.

Impact of low-dose aspirin on coronary artery spasm as assessed by intracoronary acetylcholine provocation test in Korean patients.

High-dose aspirin has been reported to aggravate coronary artery spasm (CAS). However, it is unknown whether low-dose aspirin (LDA; 100 mg) has deleterious impact on CAS. We assessed the impact of LDA on CAS induced by intracoronary acetylcholine (ACh) provocation test. A total of 2789 consecutive patients without significant coronary artery disease who underwent ACh test between November 2004 and March 2010 were enrolled. The patients were divided into two groups: the aspirin group taking LDA before ACh test (n=221) and the no aspirin group not taking aspirin (n=2568). At baseline, the prevalence of old age, diabetes mellitus, hypertension, and hyperlipidemia were higher in the aspirin group. During the ACh test, the incidence of significant CAS, ischemic chest pain, as well as severe and multivessel spasm was higher in the aspirin group. The response rate to lower ACh dose was higher in the aspirin group. Multivariate analysis showed that the previous use of LDA was an independent predictor of CAS (adjusted odds ratio, 1.6, 95% confidence interval, 1.0-2.3; p=0.031). However, it is likely that the association of LDA and CAS that we have observed is not causal but may be hypothesis generating due to significant baseline differences. Further, male gender, old age, lipid-lowering drugs, baseline spasm, and myocardial bridge were independent predictors of CAS. LDA was more frequently associated with CAS and ischemic symptoms, as well as severe and multivessel spasm, suggesting the patients who have received LDA would require more intensive medical therapies and close follow up.

Impact of heterogeneous overlapping drug-eluting stents on the arterial responses of rabbit iliac arteries: a comparison with overlapping bare metal stents.

BACKGROUND AND OBJECTIVES: Although the use of heterogeneous overlapping drug-eluting stents (DES) is not uncommon in clinical practice, whether the implantation sequences of heterogeneous DES will influence the endothelialization or arterial responses differently remains unclear. MATERIALS AND METHODS: Twenty-one rabbits were randomized to receive overlapping stents in the iliac artery for 3 months {distal sirolimus-eluting stent (SES, Cypher™)+proximal paclitaxel-eluting stent (PES, Taxus™) (C+T, n=7), distal Taxus+proximal Cypher (T+C, n=7) and bare metal stent (BMS)+BMS (B+B, n=7)}. Endothelial function was evaluated by the acetylcholine provocation test during follow-up angiography. Histopathological changes in proximal, overlapped, and distal stented segments were evaluated. RESULTS: Although the overall angiographic outcomes were comparable, late loss (mm) in the distal stented segment was higher in the B+B (0.39±0.07) and C+T (0.40±0.20) than that in the T+C (0.06±0.02) group (p<0.001). The incidence of acetylcholine-induced spasm was higher in the DES groups compared with BMS, regardless of the implantation sequences (85.7% in C+T vs. 14.3% in B+B vs. 71.4% in T+C, p=0.017). Notably, only the distal Cypher implantation group (C+T) had three cases of stent fracture. A histopathological analysis showed that despite similar arterial injury scores, Taxus and Cypher stents had higher inflammatory reactions at the overlapped and distal segments compared with those of BMS. CONCLUSION: Despite similar arterial injury, higher inflammatory reactions were observed in overlapping DES segments regardless of the implantation sequence compared with that of BMS. Moreover, DES was associated with impaired endothelial function on the adjacent non-stented segments.

'Smoker's paradox' in young patients with acute myocardial infarction.

1. Of the patients suffering from acute myocardial infarction (AMI), smokers are younger than non-smokers, which may be a major confounding factor causing 'smoker's paradox'. Therefore, in the present study we evaluated the 'smoker's paradox' in young patients with AMI.2. In all, 1218 young AMI patients (≤ 45 years of age), comprising 990 smokers and 228 non-smokers, were enrolled in the present study. In-hospital and 8 months clinical outcomes were compared between the smokers and non-smokers. 3. Baseline clinical characteristics showed that smokers were more likely to be male (97.9% vs 72.4%; P < 0.001) and had a higher rate of ST-segment elevation myocardial infarction (71.3% vs 59.5%; P = 0.001) than non-smokers. Clinical outcomes showed that smokers had lower rates of in-hospital cardiac death (0.8% vs 3.5%; P = 0.004), total death (0.8% vs 3.5%; P = 0.004) and 8 months cardiac death (1.1% vs 3.9%; P = 0.006) and total death (1.3% vs 4.4%; P = 0.005) than non-smokers. Multivariable logistic analysis showed that current smoking was an independent protective predictor of 8 months cardiac death (odds ratio (OR) 0.25; 95% confidence interval (CI) 0.07-0.92; P = 0.037) and total death (OR 0.26; 95% CI 0.09-0.82; P = 0.021). Subgroup analysis in patients who underwent percutaneous coronary intervention after AMI showed that current smoking was an independent protective predictor of 8 months total major adverse cardiac events (OR 0.47; 95% CI 0.23-0.97; P = 0.041). 4. Current smoking seems to be associated with better clinical outcomes in young patients with AMI, suggesting the existence of the 'smoker's paradox' in this particular subset of patients.

Low molecular weight heparin versus unfractionated heparin in patients with acute non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention with drug-eluting stents.

BACKGROUND: Whether low molecular weight heparin (LMWH) enoxaparin is equivalent to unfractionated heparin (UFH) in patients with non-ST-segment elevation myocardial infarction (NSTEMI) undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) remains unclear. METHODS: A total of 2397 NSTEMI patients who underwent PCI with DES received either LMWH [n=1178, subcutaneous enoxaparin 1 mg/kg, b.i.d., initiated after the patient's arrival and continued until 3-5 days after PCI plus reduced dose of UFH (50-70 U/kg) during PCI] or UFH (n=1219, 24,000U/day infusion, initiated after the patient's arrival and continued until at least 48 h after PCI). The bleeding events and clinical outcomes during in-hospital and at 8 months were compared. RESULTS: Enoxaparin group had similar incidences of cardiac death, total death, and total major adverse cardiac events (MACE) at 8 months compared with UFH group. The incidences of major and minor bleeding events were also similar between the two groups. Multivariable Cox regression analysis showed that enoxaparin group had similar incidences of cardiac death [adjusted odds ratio (OR) 1.16, 95% confidence interval (CI) 0.64-2.10, p=0.620], total death (adjusted OR 1.08, 95% CI 0.66-1.76, p=0.760), and total MACE (adjusted OR 0.94, 95% CI 0.69-1.28, p=0.692) at 8 months as compared with UFH group. CONCLUSIONS: Enoxaparin with reduced dose of UFH only during PCI as an adjunctive antithrombotic therapy in NSTEMI patients undergoing PCI with DES was safe and showed comparable 8-month clinical outcomes as compared with UFH alone.

Multivessel versus single vessel spasm, as assessed by the intracoronary acetylcholine provocation test, in Korean patients.

1. Coronary artery spasm (CAS) is known to be a major cause of myocardial ischaemia. Multivessel coronary spasm (MVS) in particular is likely to induce more severe and prolonged myocardial ischaemia than single vessel spasm (SVS). 2. In the present study, a total of 1082 consecutive patients without significant coronary artery disease who underwent an acetylcholine (ACh) provocation test between March 2004 and April 2009 were investigated. Patients were divided into three groups: an MVS group (n = 275), an SVS group (n = 376) and a non-CAS group (n = 431). Differences in clinical and angiographic characteristics following the ACh provocation test were evaluated between the MVS, SVS and non-CAS groups. 3. At baseline, patients in the MVS group had the highest prevalence of peripheral artery disease (PAD), hyperlipidaemia, smoking and old age, as well as the highest triglyceride levels. Calcium channel blockers were most frequently prescribed in MVS patients before the ACh test. During the ACh test, the highest prevalence of chest pain, ischaemic electrocardiogram changes, baseline spasms and diffuse and severe spasms were observed in the MVS group. The response rate to lower ACh doses that induce CAS was also higher in the MVS group. Multivariate analysis showed that the presence of PAD (odds ratio (OR) 2.0; P = 0.006) and baseline spasm (OR 1.4; P = 0.045) were independent predictors of ACh-induced MVS. 4. In conclusion, ischaemic symptoms, diffuse and severe spasm and baseline spasm were more frequently associated with MVS patients, suggesting more intensive medical therapies and close clinical follow up would be required for this patient group.

[Studies on six heavy metal elements dissolution characteristics of Andrographis herb by ICP-OES].

A simple and accurate method for the simultaneous determination of As, Ba, Cd, Cr, Cu and Pb in andrographis herb by inductively coupled plasma optical emission spectrometry (ICP-OES) was developed. The samples were digested by HNO3-HClO4. The digestion-determination method was evaluated with the relative standard deviations for all these elements between 2.1% and 4.6%, and the recoveries were between 92.0% and 103.2%. The measuring method was proved to be simple, reliable and highly sensitive. The dissolution characteristics of the 6 heavy metal elements in different solvents and with different extraction methods such as refluxing, soaking, and ultrasonic assisted extraction were studied. The experimental results showed that Ba was in the highest concentration followed by Cu and Cr, and the concentration of As, Pb and Cd was relatively lower in the herb. With the increase in ethanol concentration, the dissolution amount of Ba decreased but that of Cu and Cr increased, and the highest concentration of Cd was dissolved in acidic solution. Overall, Cd and Pb were difficult to dissolve out with 85% ethanol refluxing, but As dissolved comparatively more under the same condition. Comparing the extraction methods, the higher concentration of these 6 metals was obtained by refluxing water or alkaline water than that by 85% ethanol maceration. These differences might be related to the existent forms of these six elements in the herb. The determination and study on dissolution characteristics of these elements by using ICP-OES was important for rational using medicinal resources and ensuring the safety of drugs.

Low-molecular-weight heparin versus unfractionated heparin in acute ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with drug-eluting stents.

BACKGROUND: Whether low-molecular-weight heparin (LMWH) is superior to unfractionated heparin (UFH) in acute ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) remains unclear. METHODS: A total of 3,372 STEMI patients who underwent primary PCI with DESs received either LMWH (n = 1,531 patients, subcutaneous enoxaparin 1 mg/kg, bid for 3-5 days plus reduced dose of UFH [50 U/kg] during PCI) or UFH alone (n = 1,841 patients, intravenous bolus injection of 5,000 U, followed by 24,000 U/d infusion for at least 48 hours). The bleeding events and clinical outcomes during in-hospital and at 8 months were compared. RESULTS: The incidences of major and minor bleeding events were similar between the 2 groups. Multivariable Cox regression analysis showed that LMWH group had lower incidences of cardiac death (adjusted odds ratio [OR] 0.55, 95% CI 0.39-0.77, P < .001), total death (adjusted OR 0.50, 95% CI 0.37-0.68, P < .001), and total major adverse cardiac events (adjusted OR 0.77, 95% CI 0.62-0.95, P = .017) at 8 months as compared with UFH group. Similar results were obtained across different subgroups including different DESs, age, and sex. CONCLUSIONS: The LMWH enoxaparin combined with reduced dose of UFH (50 U/kg) administration as an adjunctive antithrombotic therapy in STEMI patients undergoing primary PCI with DESs seems to be safe and efficacious. However, randomized clinical trials are needed to confirm this conclusion.

Clinical characteristics and mid-term outcomes of acute myocardial infarction patients with prior cerebrovascular disease in an Asian population: Lessons from the Korea Acute Myocardial Infarction Registry.

1. The aim of the present study was to evaluated the impact of prior cerebrovascular disease (CVD) on the clinical characteristics and mid-term clinical outcomes of patients with acute myocardial infarction (AMI) in the era of drug-eluting stents. 2. Data from 12 914 patients with acute myocardial infarction who were enrolled in the Korea Acute Myocardial Infarction Registry were analysed retrospectively from November 2005 to December 2007. Prior CVD was defined as having had one or more events of ischaemic or haemorrhagic stroke or a transient ischaemic attack. 3. Of the 12 914 patients reviewed, 906 (7.0%) were found to have had prior CVD. Patients with CVD were older, were more likely to be women and were more likely to have hypertension and diabetes than those without CVD. Patients with prior CVD presented more often with non-ST-segment elevation myocardial infarction and higher Killip class than those without CVD. Furthermore, patients with CVD received less percutaneous coronary intervention (PCI) or thrombolysis compared with those without CVD. Although intensive medical therapy was equal in both groups, clinical outcomes at 8 months showed that patients with CVD had a higher incidence of cardiac death (adjusted odds ratio (OR) 1.42; 95% confidence interval (CI) 1.14-1.76; P = 0.002) and total death (adjusted OR 1.50; 95% CI 1.25-1.81; P < 0.001) than those without CVD. 4. In conclusion, patients with prior CVD presented with worse clinical characteristics on admission and were less likely to receive PCI or thrombolysis than those without CVD. Given the poorer mid-term clinical outcomes, more intensive and aggressive management shouldis recommended for patients with prior CVD to improve their long-term clinical outcome.