Indigo enhances wound healing activity of Caco-2 cells via activation of the aryl hydrocarbon receptor.

Indigo Naturalis, also known as Qing Dai (QD) is a compound obtained from Indigofera tinctoria, Isatis tinctoria, and Polygonum tinctoria and is known to ameliorate refractory ulcerative colitis (UC) by an unknown mechanism. QD maintains both homeostasis and the integrity of colon epithelia in mice that have experimentally induced colitis. The primary component of QD, indigo, comprises 42.4% of the compound. Indigo efficiently suppresses rectal bleeding and reduces the erosion of the colon epithelium, whereas it does not reduce weight loss or increase survival in a certain condition. Indigo is a ligand of the aryl hydrocarbon receptor (AhR), which is involved in the anti-colitis activity of QD. Here we investigate the effects of indigo on wound (erosion) closure in colon epithelial cells. Oral administration of indigo induced expression of Cytochrome P450 1A1 (Cyp1a1) in the colon but not in the liver, suggesting that indigo stimulates AhR from the luminal side of the colon. The erosion-closure activity tested in the scratch assays using Caco-2 cells was accelerated by addition of QD and indigo to the culture medium. QD and indigo also induced nuclear localization of AhR and expression of CYP1A1 in the Caco-2 cells. Acceleration of scratch wound closure was abolished by addition of the AhR-antagonist CH223191. Cell proliferation and actin polymerization were also shown to contribute to erosion closure. The results suggest that indigo exerts its erosion-healing effects by increasing proliferation and migration of colon epithelial cells via activation of AhR in intestinal epithelia.

Obstructive sleep apnoea inhibits the recovery of left ventricular function in patients with acute myocardial infarction.

AIMS: It has been suggested that obstructive sleep apnoea syndrome (OSA) may be a direct cause of left ventricular (LV) systolic dysfunction. This study was designed to examine our hypothesis that OSA inhibits the recovery of LV function in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: Our 86 consecutive first-AMI patients underwent primary percutaneous coronary intervention (PCI). All patients underwent polysomnography and OSA was defined as an apnoea-hypoapnoea index (AHI) > or =15 events/h, of which more than 50% were obstructive. Left ventriculograms immediately after PCI and at 21 days were used to evaluate LV ejection fraction (LVEF), LV end-diastolic volume index, and regional wall motion (RWM) within the infarct area. OSA was observed in 37 patients (43%). All three indices of LV function after primary PCI were comparable between the two groups. Increases in LVEF and RWM during admission were significantly lower in OSA patients than those without OSA (delta LVEF: -0.3+/-9.6 vs. 7.4+/-7.2%, P < 0.001; delta RWM: 0.26+/-1.04 SD/chord vs. 1.16+/-1.20 SD/chord, P = 0.002). Multiple regression analysis showed that AHI correlated negatively with delta LVEF and delta RWM. CONCLUSION: The novel finding is that OSA may inhibit the recovery of LV function in patients with AMI.

Serum amyloid a protein as a predictor of cardiac rupture in acute myocardial infarction patients following primary coronary angioplasty.

BACKGROUND: The predictors of cardiac rupture (CR) in patients with acute myocardial infarction (AMI) treated with successful primary coronary angioplasty have not been identified. METHODS AND RESULTS: Of 433 consecutive AMI subjects who underwent reperfusion by primary coronary angioplasty within 24 h of onset, CR occurred in 11 (2.5%), free wall rupture in 9, and ventricular septal perforation in 2. Rates of females, diabetes mellitus and anterior infarction were higher in the group of CR patients than in the others (p < 0.05). There were no significant differences between the 2 groups in terms of left ventricular (LV) function soon after recanalization, such as LV ejection fraction, regional wall motion, or end-diastolic volume index. Plasma levels of both high-sensitivity C-reactive protein (hsCRP) and serum amyloid-A protein (SAA) were significantly higher in the CR patients than in the others (hsCRP: 6.7 +/- 6.7 mg/dl vs 3.3 +/- 3.8 mg/dl, p = 0.007; SAA: 699 +/- 812 microg/dl vs 208 +/- 273 microg/dl, p < 0.0001). Multivariate analysis identified SAA as an independent predictor of CR (risk ratio: 8.8, 95% confidence interval: 1.7-25.6, p < 0.05). Conclusions In patients with AMI treated with primary coronary angioplasty, inflammation may be closely related to CR, for which SAA is a useful predictor.

Predictors of sub-acute stent thrombosis in acute myocardial infarction patients following primary coronary stenting with bare metal stent.

BACKGROUND: The aim of the present study was to identify the relationship between sub-acute stent thrombosis (SAT) and acute-phase inflammatory reactants, such as high-sensitivity C-reactive protein (hs-CRP) and serum amyloid-A protein (SAA), in patients with acute myocardial infarction (AMI) successfully treated with primary coronary stenting. METHODS AND RESULTS: The 381 consecutive AMI subjects were reperfused by primary coronary stenting within 24 h of onset. SAT was confirmed angiographically in 10 patients (2.6%). There were no significant differences between the patients with or without SAT in terms of patient characteristics, Killip classification on admission, or stent diameter, nor were there significant differences between the 2 groups in terms of left ventricular function soon after stenting (left ventricular ejection fraction) or end-diastolic volume index. The plasma levels of both hs-CRP and SAA were significantly higher in the SAT patients than in the others (hs-CRP: 6.7+/-6.7 mg/dl vs 3.3+/-3.8 mg/dl, p=0.007; SAA: 699+/-812 mug/dl vs 208+/-273 mug/dl, p<0.0001). Multivariate analysis identified SAA as an independent predictor of SAT (risk ratio: 4.9, 95% confidence interval: 1.7-14.9, p<0.05). CONCLUSION: In patients with AMI who are treated with primary coronary stenting, inflammation may be closely related to SAT, for which SAA is a useful predictor.

Prognostic significance of time-delay to peak creatine kinase after direct percutaneous coronary intervention in acute myocardial infarction patients.

The aim of the present study was to investigate the prognostic significance of time-delay to peak creatine kinase (CK) after successful direct percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Our 240 consecutive first AMI attack subjects admitted within 5 hours from onset were successfully reperfused by direct PCI therapy. Subjects were divided into two groups according to the upper quartile value of peak-CK time from onset, the early peak-CK group (peak-CK time < or = 16 hours from onset, n = 180) and the late peak-CK group (peak-CK time > 16 hours, n = 60). (I) The early ST-segment resolution rate was lower in the late peak-CK group compared with the early peak-CK group (P < 0.05), and there were significantly fewer patients with preinfarction angina pectoris in the late peak-CK group than in the early peak-CK group (P < 0.01). (II) LVEF in the chronic stage was significantly lower in the late peak-CK group than in the early peak-CK group (49 +/- 13% versus 57 +/- 13%, P < 0.001). (III) There were significantly more patients with major complications in the late peak-CK group than in the early peak-CK group (required CABG: 10% versus 3%, P < 0.05; cardiac death: 18% versus 3%, P = 0.0001). (IV) Multivariate analysis identified late peak-CK as an independent predictor of cardiac death (Odds ratio 7.91, 95% C.I. 1.40-44.11, P < 0.05). In patients with AMI, the time-delay to peak-CK after successful direct PCI may be closely related to left-ventricular systolic dysfunction and poor patient outcome, including mortality.

Prognostic value of serum amyloid A protein in patients with acute myocardial infarction.

BACKGROUND: The relationship between plasma levels of serum amyloid A protein (SAA) concentrations and clinical course (including mortality) was investigated in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: The study enrolled 280 consecutive AMI patients who were admitted within 10 h of onset and were successfully reperfused by primary percutaneous coronary intervention. Plasma SAA concentrations were evaluated at 24 h after onset. The threshold of the upper quintile (325 mug/dl) was used to divide patients into 2 groups: either a high SAA (H group: > or =325 mug/dl; n=56) or low SAA (L group: <325 microg/dl; n=224). (I) Left ventricular (LV) ejection fraction in the chronic phase was significantly less in the H group than in the L group (52+/-14% vs 57+/-13%, p=0.03). (II) There were significantly more major complications in the H group than in the L group (cardiac rupture: p=0.0007, cardiogenic shock: p<0.0001; subacute thrombosis: p=0.0007; cardiac death: p=0.0003). (III) Multivariate analysis identified SAA as an independent predictor of 6-month mortality in AMI patients (risk ratio: 5.8, 95%confidence interval: 1.3-27.7, p=0.03). CONCLUSIONS: In the setting of AMI, plasma SAA concentrations may be closely related to LV systolic dysfunction and poor patient outcomes, including mortality.

Clinical outcomes and left ventricular function in diabetic patients with acute myocardial infarction treated by primary coronary angioplasty.

The objective of the present study was to compare left ventricular (LV) function and clinical outcomes in diabetics versus nondiabetics with acute myocardial infarction (AMI) treated by primary coronary angioplasty. A total of 327 consecutive AMI subjects were reperfused by primary coronary angioplasty within 12 hours from onset. Diabetes mellitus (DM) was present in 104 of the 327 patients. LV function was serially determined by left ventriculograms taken in the acute and chronic phases (6 months after onset). (I) The early ST-segment resolution rate was lower in DM patients compared with non-DM patients (59% versus 83%, P < 0.0001). (II) During a 6-month follow-up, the percentages of target vessel revascularization (TVR), coronary aorta bypass grafting (CABG), and cardiac death were higher in the DM patients compared with the non-DM patients (TVR: 29% versus 19%; P < 0.05, CABG: 10% versus 5% ; P < 0.05, cardiac death: 12% versus 4%; P = 0.01). (III) The differences in left ventricular ejection fraction (LVEF) between two stages (delta-LVEF) were significantly lower in the DM patients than the non-DM patients (1 +/- 9% versus 7 +/- 10%, P < 0.0001). (IV) Multivariate analysis identified DM as an independent predictor of cardiac death (Odds ratio 5.5, 95% CI, 1.3-23.7, P < 0.05) and as a sole independent predictor of LVEF deterioration (Odds ratio 5.8, 95% CI, 2.8-11.8, P < 0.001). In patients with AMI treated using primary coronary angioplasty, DM is closely related to left-ventricular systolic dysfunction and a poor patient outcome, including mortality.

Clinical significance of acute-phase endothelin-1 in acute myocardial infarction patients treated with direct coronary angioplasty.

BACKGROUND: The aim of the present study was to investigate the relationship between plasma concentrations of endothelin (ET)-1 and clinical outcome (including mortality) and left ventricular (LV) systolic function in acute myocardial infarction (AMI). METHODS AND RESULTS: The study group comprised 110 consecutive first-AMI patients who were successfully reperfused by primary coronary intervention. Plasma ET-1 concentrations were evaluated 24 h from onset and the patients were divided into 2 groups according to the median value, either a high group (H group: > or = 2.90 pg/ml plasma ET-1; n = 55) or low group (L group: < 2.90 pg/ml plasma ET-1; n = 55). Major complications and LV systolic function were monitored in the 2 groups. Both highly sensitive C-reactive protein (hs-CRP) and brain natriuretic peptide (BNP) showed a significant positive correlation with ET-1 (BNP: r = 048, p < 0.0001, hs-CRP: r = 0.43, p < 0.001). Chronic stage left ventricular ejection fraction (LVEF) and left ventricular end-diastolic volume index (LVEDVI) were significantly poorer in the H group (LVEF: 51+/-15% vs 60+/-13%, p = 0.003, LVEDVI: 74+/-19 ml/m2 vs 66+/-14 ml/m2, p < 0.05). There were significantly more major complications in the H group than in the L group (cardiogenic shock: 18% vs 5%, p = 0.04; cardiac death: 13% vs 0%, p < 0.01). CONCLUSIONS: In the setting of AMI, plasma ET-1 concentrations may be closely related to LV systolic dysfunction and poor patient outcome, including mortality.

Predictors of mortality in patients with acute myocardial infarction and cardiogenic shock.

BACKGROUND: Although cardiogenic shock (CS) is the leading cause of death for acute myocardial infarction (AMI) patients, reliable predictive factors in the acute stage, such as cardiovascular peptides, have not yet been identified. METHODS AND RESULTS: In 42 consecutive AMI patients with CS on admission, successfully treated by primary percutaneous coronary intervention (PCI) within 12 h of onset, related factors including brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), renin, aldosterone, catecholamines, and adrenomedullin, were investigated 24 h from onset, as well as the 1-year mortality rates. During the 12-month follow-up period, 15 patients died from cardiovascular causes (group D). There were no significant differences in patient characteristics, angiographic findings, and left ventricular systolic function between group D subjects and the survivors (group S: n=27). Multivariate analysis identified high levels of adrenomedullin as an independent predictor of 1-year mortality (risk ratio: 6.42, 95% confidence interval, 1.49-43.31, p<0.05). CONCLUSIONS: The acute-phase plasma concentration of adrenomedullin may be a reliable predictor of mortality in patients with AMI complicated by CS and successfully treated by direct PCI, as may be BNP concentration, peak-creatine kinase value, and ventricular fibrillation.

Segmental mediolytic arteriopathy involving celiac to splenic and left renal arteries.

A 46-year-old man presented with a huge splenic artery dissecting aneurysm that had been incidentally found and was successfully resected before rupture. The histopathologic findings were compatible with segmental mediolytic arteriopathy (SMA). Simultaneous involvement of the left renal and right common iliac artery was observed. The patient was also found to have an adrenocortical adenoma, gastrointestinal stromal tumor, hepatocellular carcinoma and schizophrenia. The relationship between SMA and other accompanying diseases was discussed.