Background

Many patients who survive a myocardial infarction (MI) remain at risk of sudden cardiac death despite revascularization and optimal medical treatment. We used the modified moving average (MMA) method to assess the utility of T-wave alternans (TWA) and heart rate turbulence (HRT) as risk markers in MI patients with or without diabetes mellitus (DM).

Methods

We prospectively enrolled 248 consecutive patients: 96 with MI (post-MI patients); 77 MI with DM (post-MI + DM patients); 75 controls without cardiovascular disease (group control). Both TWA and HRT were measured on ambulatory electrocardiograms (AECGs). HRT was assessed by two parameters ─ turbulence onset (TO) and turbulence slope (TS). HRT was considered positive when both TO ≥0% and TS ≤2.5 ms/R-R interval were met. The endpoint was cardiac mortality.

Results

TWA values differed significantly between MI and controls. Post-MI + DM patients had higher TWA values than post-MI patients (58 ± 21 μV VS 52 ± 18 μV, P = 0.029). Impaired HRT--increased TO and decreased TS were observed in MI patients with or without DM. During follow-up of 578 ± 146 days, cardiac death occurred in ten patients and three of them suffered sudden cardiac death (SCD). Multivariate analysis determined that a HRT-positive outcome [HR (95% CI): 5.01, 1.33–18.85; P = 0.017], as well as the combination of abnormal TWA (≥47 μV) and positive HRT had significant association with the endpoint [HR (95% CI): 9.08, 2.21–37.2; P = 0.002)].

Conclusion

This study indicates that AECGs-based TWA and HRT can predict cardiac mortality in MI patients with or without DM. Combined analysis TWA and HRT may be a convenient and useful method of identifying patients at high risk for cardiovascular death.

Background

Epithelial-mesenchymal transition of tubular epithelial cells, which is characterized by a loss of epithelial cell characteristics and a gain of ECM-producing myofibroblast characteristics, is an essential mechanism that is involved in tubulointerstitial fibrosis, an important component of the renal injury that is associated with diabetic nephropathy. Under diabetic conditions, p38 MAPK activation has been reported in glomeruli and mesangial cells; however, studies on p38 MAPK in TECs are lacking. In this study, the role of p38 MAPK in AP-1 activation and in the EMT in the human proximal tubular epithelial cell line (HK-2) under high glucose concentration conditions is investigated.

Methodology/Principal Findings

A vector for small interfering RNA that targets p38 MAPK was constructed; the cells were then either transfected with p38 siRNA or pretreated with a chemical inhibitor of AP-1 and incubated with low glucose plus TGF-β1 or high glucose for 48 h. Cells that were not transfected or pretreated and were exposed to low glucose with or without TGF-β1 or high glucose for 48 h were considered to be the controls. We found that high glucose induced an increase in TGF-β1. And high glucose-induced p38 MAPK activation was inhibited by p38 siRNA (P<0.05). A significant decline in E-cadherin and CK expression and a notable increase in vimentin and α-SMA were detected when exposed to low glucose with TGF-β1 or high glucose, and a significant raise of secreted fibronectin were detected when exposed to high glucose; whereas these changes were reversed when the cells were treated with p38 siRNA or AP-1 inhibitor (P<0.05). AP-1 activity levels and Snail expression were up-regulated under high glucose conditions but were markedly down-regulated through knockdown of p38 MAPK with p38 siRNA or pretreatment with AP-1 inhibitor (P<0.05).

Conclusion

This study suggests that p38 MAPK may play an important role in the high glucose-induced EMT by activating AP-1 in tubular epithelial cells.

In the title dihalogenated trichodermin mol­ecule, C17H24Br2O4 (systematic name: 9,10-dibromo-12,13-epoxy­trichothec-9-en-4β-yl acetate), the five-membered ring displays an envelope conformation, whereas the two six-membered rings show the same conformation, viz. chair. As for the seven-membered ring, the dihedral angle between the mean planes formed by the four C atoms of the envelope unit and the three C and one O atoms of the six-membered chair is 69.08 (4)°; these two mean planes are nearly perpendicular to the ep­oxy ring with angles of 87.53 (4) and 88.67 (4)°, respectively.