Six-Month Comparison of Coronary Endothelial Dysfunction Associated With Sirolimus-Eluting Stent Versus Paclitaxel-Eluting Stent

ObjectivesThis study was designed to investigate whether endothelial dysfunction is related to drug-eluting stent (DES) implantation at 6 months after stenting.BackgroundCurrent available DES could delay vessel healing and subsequently impair endothelial function.MethodsEndothelial function was estimated at 6-month follow-up in 75 patients (31 men, mean age 62.1 years) with a DES (39 sirolimus-eluting stents [SES], 36 paclitaxel-eluting stents [PES]), and 10 patients with a bare-metal stent (BMS) to the left anterior descending artery, by incremental acetylcholine (Ach) infusion (20 μg/min, 50 μg/min, 100 μg/min) and nitrate (200 μg/min) into the left coronary ostium. Vascular responses were quantitatively measured in arterial segments 5 mm proximal and distal to DES and compared with corresponding segments in the BMS group and midsegments in the left circumflex artery as a reference nonstented artery. All antianginal agents were withheld for at least 72 h before coronary angiography.ResultsGreater vasoconstriction to Ach was observed in both the SES and PES groups than in the BMS group or control segments of left circumflex artery. Vasoconstriction to Ach was more prominent in arterial segments distal to stents in both SES and PES groups compared with those in the BMS group (p < 0.001). The degree of vasoconstriction to Ach was similar between the SES and PES groups. Endothelium-independent vasodilatation to nitrate did not differ significantly between the study groups.ConclusionsAbnormal vasoconstriction to Ach was found in the SES and PES groups, especially in arterial segments distal to DES at 6 months after stenting, which suggests that DES has a potential long-term adverse effect on local coronary endothelial dysfunction

Fimasartan Ameliorates Nonalcoholic Fatty Liver Disease through PPAR δ

To investigate the effects of fimasartan on nonalcoholic fatty liver disease in hyperlipidemic and hypertensive conditions, the levels of biomarkers related to fatty acid metabolism were determined in HepG2 and differentiated 3T3-L1 cells treated by high fatty acid and liver and visceral fat tissue samples of spontaneously hypertensive rats (SHRs) given high-fat diet. In HepG2 cells and liver tissues, fimasartan was shown to increase the protein levels of peroxisome proliferator-activated receptor delta (PPARδ), phosphorylated 5′ adenosine monophosphate-activated protein kinase (p-AMPK), phosphorylated acetyl-CoA carboxylase (p-ACC), malonyl-CoA decarboxylase (MCD), medium chain acyl-CoA dehydrogenase (MCAD), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and it led to a decrease in the protein levels of 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSDH1), fatty acid synthase (FAS), and tumor necrosis factor-alpha (TNF-α). Fimasartan decreased lipid contents in HepG2 and differentiated 3T3-L1 cells and liver tissues. In addition, fimasartan increased the adiponectin level in visceral fat tissues. The antiadipogenic effects of fimasartan were offset by PPARδ antagonist (GSK0660). Consequently, fimasartan ameliorates nonalcoholic fatty liver disease mainly through the activation of oxidative metabolism represented by PPARδ-AMPK-PGC-1α pathway

Bare-metal stents versus drug-eluting stents in large (≥3.5mm) single coronary artery: Angiographic and clinical outcomes at 6 months

SummaryBackgroundAlthough drug-eluting stents (DES) have been shown to dramatically reduce restenosis and improve the rate of event-free survival in large randomized trials, the benefit of DES appears to be limited to restenosis. In large arteries, it is not clear which type of stent is more superior in angiographic and clinical outcomes between DES and bare-metal stents (BMS). We compared the angiographic and clinical outcomes of DES versus BMS in large arteries (≥3.5mm).MethodTwo hundred and forty patients from March 2002 to March 2007 received stents; 196 patients were treated with DES (44.9% sirolimus-eluting stents; 43.9% paclitaxel-eluting stents; 11.2% zotarolimus-eluting stents) and 44 with cobalt–chromium BMS for single de novo lesions in a large vessel. All subjects received aspirin, clopidogrel, and/or cilostazol as the standard antiplatelet regimen. The angiographic and clinical outcomes were evaluated at 6 months.ResultsFor the baseline characteristics, there were no significant differences between the DES and BMS groups. In addition, for the initially implanted stent there was no difference in the length, stent diameter, and lesion site between the two groups. After 6 months, the follow-up angiogram showed that in-stent diameter restenosis and late loss was more common with BMS than DES (39±21% vs. 19±17%, p=0.007; 1.44±0.83mm vs. 0.62±0.58mm, p=0.009, respectively). However, the target-lesion revascularization/target-vessel revascularization, and total major adverse cardiac events showed no significant differences between the groups (5.3% vs. 3.6%, p=0.62; 5.3% vs. 4.6%, p=0.86, respectively).ConclusionThe DES and cobalt–chromium BMS placed in large coronary arteries showed equally favorable 6-month clinical outcomes, although the 6-month angiographic results appeared more favorable in the DES group than in the BMS group

Evidence for Two Modes of Synergistic Induction of Apoptosis by Mapatumumab and Oxaliplatin in Combination with Hyperthermia in Human Colon Cancer Cells

Colorectal cancer is the third leading cause of cancer-related mortality in the world-- the main cause of death from colorectal cancer is hepatic metastases, which can be treated with isolated hepatic perfusion (IHP). Searching for the most clinically relevant approaches for treating colorectal metastatic disease by isolated hepatic perfusion (IHP), we developed the application of oxaliplatin concomitantly with hyperthermia and humanized death receptor 4 (DR4) antibody mapatumumab (Mapa), and investigated the molecular mechanisms of this multimodality treatment in human colon cancer cell lines CX-1 and HCT116 as well as human colon cancer stem cells Tu-12, Tu-21 and Tu-22. We showed here, in this study, that the synergistic effect of the multimodality treatment-induced apoptosis was caspase dependent and activated death signaling via both the extrinsic apoptotic pathway and the intrinsic pathway. Death signaling was activated by c-Jun N-terminal kinase (JNK) signaling which led to Bcl-xL phosphorylation at serine 62, decreasing the anti-apoptotic activity of Bcl-xL, which contributed to the intrinsic pathway. The downregulation of cellular FLICE inhibitory protein long isoform (c-FLIPL) in the extrinsic pathway was accomplished through ubiquitination at lysine residue (K) 195 and protein synthesis inhibition. Overexpression of c-FLIPL mutant (K195R) and Bcl-xL mutant (S62A) completely abrogated the synergistic effect. The successful outcome of this study supports the application of multimodality strategy to patients with colorectal hepatic metastases who fail to respond to standard chemoradiotherapy that predominantly targets the mitochondrial apoptotic pathway. © 2013 Song et al

Localized Gastric Amyloidosis with Kappa and Lambda Light Chain Co-Expression

Esophagogastroduodenoscopy for cancer screening was performed in a 55-year-old woman as part of a health screening program, and revealed a depressed lesion approximately 20 mm in diameter in the lesser curvature of the mid-gastric body. Several biopsy specimens were collected as the lesion resembled early gastric cancer; however, histopathologic evaluation revealed chronic active gastritis with an ulcer and amorphous eosinophilic material deposition. Congo red staining identified amyloid proteins, and apple-green birefringence was shown using polarized light microscopy. Immunohistochemical staining revealed the presence of kappa and lambda chain-positive plasma cells. There was no evidence of underlying plasma cell dyscrasia or amyloid deposition in other segments of the gastrointestinal tract. Echocardiography and computed tomography of the chest, abdomen, and pelvis did not show any significant findings. Thus, the patient was diagnosed with localized gastric amyloidosis with kappa and lambda light chain coexpression

Characterization of glucose uptake metabolism in visceral fat by 18 F-FDG PET/CT reflects inflammatory status in metabolic syndrome.

OBJECTIVE:The inflammatory activity of visceral adipose tissue (VAT) is elevated in metabolic syndrome (MS), and associated with vulnerability to atherosclerosis. Inflammation can be assessed by glucose uptake in atherosclerotic plaques. We investigated whether the glucose uptake of VAT, assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), is associated with systemic inflammatory status, and related to the number of MS components. METHODS:18F-FDG PET/CT was performed in a total of 203 participants: 59 without MS component; M(0), 92 with one or two MS components; M(1-2), and 52 with MS. Glucose uptake in VAT was evaluated using the mean standardized uptake value (SUVmean) and the maximum SUV (SUVmax). Glucose uptakes of immune-related organs such as the spleen and bone marrow (BM) were evaluated using the SUVmax. RESULTS:VAT SUVmax correlated with high-sensitivity C-reactive protein (hsCRP) and the SUVmax of spleen and BM, which reflect the status of systemic inflammation. Both hsCRP and the SUVmax of the spleen and BM were higher in the MS group than in the M(1-2) or M(0) groups. In VAT, SUVmax increased with increasing number of MS components, while SUVmean decreased. CONCLUSIONS:The SUVmax and SUVmean of VAT assessed by 18F-FDG PET/CT reflected inflammation-driven unique glucose metabolism in the VAT of MS patients, distinct from that of atherosclerotic plaques