Serum free fatty acids are associated with severe coronary artery calcification, especially in diabetes: a retrospective study.

BACKGROUND: Serum free fatty acid (FFA) concentrations are associated with coronary heart disease and diabetes mellitus (DM). Few studies focused on the relationship between serum FFA levels and coronary artery calcification (CAC). METHODS: This was a retrospective, single-centered study recruiting patients underwent FFA quantification, coronary angiography and intravascular ultrasound (IVUS). CAC severity was assessed with the maximum calcific angle (arc) of the calcified plaque scanned by IVUS. Patients with an arc ≥ 180° were classified into the severe CAC (SCAC) group, and those with an arc < 180° were classified into the non-SCAC group. Clinical characteristics, serum indices were compared between 2 groups. Logistic regression, receiver operating characteristic (ROC) curves and area under the curves (AUC) were performed. RESULTS: Totally, 426 patients with coronary artery disease were consecutively included. Serum FFA levels were significantly higher in the SCAC group than non-SCAC group (6.62 ± 2.17 vs. 5.13 ± 1.73 mmol/dl, p < 0.001). Logistic regression revealed that serum FFAs were independently associated with SCAC after adjusting for confounding factors in the whole cohort (OR 1.414, CI 1.237-1.617, p < 0.001), the non-DM group (OR 1.273, CI 1.087-1.492, p = 0.003) and the DM group (OR 1.939, CI 1.388-2.710, p < 0.001). ROC analysis revealed a serum FFA AUC of 0.695 (CI 0.641-0.750, p < 0.001) in the whole population. The diagnostic predictability was augmented (AUC = 0.775, CI 0.690-0.859, p < 0.001) in the DM group and decreased (AUC = 0.649, CI 0.580-0.718, p < 0.001) in the non-DM group. CONCLUSIONS: Serum FFA levels were independently associated with SCAC, and could have some predictive capacity for SCAC. The association was strongest in the DM group.

1-butyltryptophan inhibits cell proliferation, migration, and invasion through the Akt pathway in human gastric cancer cells.

We have previously demonstrated that novel 1-alkyl-tryptophan analogs 1-butyltryptophan (1-BT) can serve as a potential antitumor agent. However, the molecular mechanisms of 1-BT on cancer cells remain to be elucidated. The effect of 1-BT on cell proliferation was detected by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and clone formation assay in SGC7901 and AGS cells. Cell cycle was determined by flow cytometry. Cell migration and invasion was determined by wound healing assay and transwell assay. The expression of cyclin-dependent kinase 4 (CDK4), cyclin D1, p16, PCNA, phosphorylated Akt, total Akt, phosphorylated ERK1/2, and total ERK1/2 was examined using Western blotting. Our data demonstrated that 1-BT inhibited cell proliferation in a dose- and time-dependent manner by the downregulation of expression of cyclin D1 and CDK4 and by the upregulation of p16 expression. The inhibition of cell growth was also demonstrated by cell cycle arrest at the G1/S phase. Furthermore, 1-BT inhibited cell migration and invasion in SGC7901 cells. In addition, we found that phosphorylated Akt was suppressed in 1-BT treated SGC7901 cells. Overexpression of activated Akt reversed the effects of 1-BT on cell migration and invasion in SGC7901 cells. These results indicated that 1-BT inhibited gastric cancer cells proliferation and migration through the Akt pathway, which has the potential clinical significance in the prevention and treatment of gastric cancer.

Endocardial focal activation originating from Purkinje fibers plays a role in the maintenance of long duration ventricular fibrillation.

AIM: To determine the role of repetitive endocardial focal activations and Purkinje fibers in the maintenance of long duration ventricular fibrillation (LDVF, VF>1 minute) in canine hearts in vivo. METHODS: The study was conducted in electrophysiological laboratory of Shanghai Ruijin hospital from July 2010 to August 2012. A 64-electrode basket was introduced through a carotid artery into the left ventricle (LV) of 11 beagle dogs for global endocardial electrical mapping. In the Lugol's solution group (n=5), the subendocardium was ablated by washing with Lugol's solution. In the control group, (n=6) saline was used for ablation. Before and after saline or Lugol ablation, we determined QRS duration and QT/QTc interval in sinus rhythm (SR). We also measured the activation rates in the first 2 seconds of each minute during 7 minutes of VF for each group. If VF terminated spontaneously in less than 7 minutes, the VF segments used in activation rate analysis were reduced accordingly. RESULTS: At the beginning of VF there was no difference between the groups in the activation rate. However, after 1 minute of LDVF the Lugol's solution group had significantly slower activation rate than the control group. In the control group, all episodes of LDVF (6/6) were successfully sustained for 7 minutes, while in the Lugol's solution group 4/5 episodes of LDVF spontaneously terminated before 7 minutes (4.8±1.4 minutes) (P=0.015). In the control group, at 5.1±1.3 minutes of LDVF, a successive, highly organized focal LV endocardial activation pattern was observed. During this period, activations partly arose in PF and spread to the working ventricular myocardium. Mapping analysis showed that these events were consistent with repetitive endocardial focal activations. No evidence of similar focal activations was observed in the Lugol's solution group. CONCLUSIONS: Repetitive endocardial focal activations in the LV endocardium may be associated with activation of subendocardial PFs. This mechanism may play an important role in the maintenance of LDVF.

Defibrillation threshold varies during different stages of ventricular fibrillation in canine hearts.

BACKGROUND: Recent studies have shown that short duration ventricular fibrillation (SDVF) and long duration ventricular fibrillation (LDVF) are maintained by different mechanisms. The objective of this study is to evaluate how the defibrillation threshold (DFT) varies over the duration of fibrillation since the mechanism of VF maintenance changes as VF progresses. METHODS: Twelve canines were randomly divided into two groups (Group A and B, n=6 each). DFTs were measured three times in each group: SDVF (20s), LDVF (3min in Group A and 7min in Group B) and the first episode of refibrillation after successful defibrillation for LDVF. Two 64-electrode baskets used to globally map the endocardium were deployed into the left ventricle and right ventricle, respectively. RESULTS: LDVF-DFT in Group A was significantly higher than that of Group B (628±98V vs 313±81V, P<0.001). In Group B, the DFT of refibrillation was significantly increased compared with the LDVF-DFT (570±199V vs 313±81V, P=0.035) but did not differ from the DFT of refibrillation in Group A (570±199V vs 638±116V, P=0.39). Highly synchronised activation patterns on the left ventricular endocardium were observed between 3 and 7min of LDVF in Group B but not within 3min-LDVF in Group A or during refibrillation in each group. CONCLUSIONS: DFT varied during different stages of VF. The highly synchronised activation patterns exhibiting after 3min VF might contribute to the decreased LDVF-DFT.