Primary Angioplasty in a Catastrophic Presentation: Acute Left Main Coronary Total Occlusion—The ATOLMA Registry

Objectives. To determine the outcome predictors of in-hospital mortality in acute total occlusion of the left main coronary artery (ATOLMA) patients referred to emergent angioplasty and to describe the clinical presentation and the long-term outcome of these patients.Background. ATOLMA is an uncommon angiographic finding that usually leads to a catastrophic presentation. Limited and inconsistent data have been previously reported regarding true ATOLMA, yet comprehensive knowledge remains scarce.Methods. This is a multicenter retrospective cohort that includes patients presenting with myocardial infarction due to a confirmed ATOLMA who underwent emergency percutaneous coronary intervention (PCI).Results. In the period of the study, 7930 emergent PCI were performed in the five participating centers, and 46 of them had a true ATOLMA (0.58%). At admission, cardiogenic shock was present in 89% of patients, and cardiopulmonary resuscitation was required in 67.4%. All the patients had right dominance. Angiographic success was achieved in 80.4% of the procedures, 13 patients (28.2%) died during the catheterization, and the in-hospital mortality rate was 58.6% (27/46). At one-year and at the final follow-up, 18 patients (39%) were alive, including four cases successfully transplanted. Multivariate analysis showed that postprocedural TIMI flow was the only independent predictor of in-hospital mortality (OR 0.23, (95% CI 0.1-0.36),p<0.001).Conclusions. Our study confirms that the clinical presentation of ATOLMA is catastrophic, presenting a high in-hospital mortality rate; nevertheless, primary angioplasty in this setting is feasible. Postprocedural TIMI flow resulted as the only independent predictor of in-hospital mortality. In-hospital survivors presented an encouraging outcome. ATOLMA and left dominance could be incompatible with life

Concentration-dependent effects of resveratrol and metabolites on the redox status of human erythrocytes in single-dose studies

AbstractDietary trans-resveratrol (RES) is rapidly metabolized into sulfated and glucuronated conjugates in humans. This study focused on the in vitro determination of the antioxidant capacity of RES and its main physiological metabolites and on its relevance in vivo. In vitro, RES, RES-3-O-sulfate (R3S) and 3-O-glucuronide (R3G) showed antioxidant activities at a concentration of 1mM when compared to Trolox using an assay in which the antioxidant inhibits iron-induced linoleic acid oxidation: 0.87±0.08mM Trolox equivalents (TE) for RES, 0.52±0.01mM TE for R3S and 0.36±0.02mM TE for R3G. At a concentration of 1μM, compounds promoted linoleic acid peroxidation (RES −0.30±0.09mM TE, R3S −0.48±0.05mM TE and R3G −0.57±0.07mM TE). To elucidate whether these effects were reflected in vivo, total antioxidant capacity, reactive oxygen species (ROS), conjugated fatty acid dienes (CD), superoxide dismutase (SOD) and catalase (CAT) activities were determined in human plasma and erythrocytes over 24h, after oral intake of either 0.05g RES as piceid or 5g RES. Oral administration of RES did not show an impact on total antioxidant capacity, ROS or CD. However, enzymatic activities of ROS scavenging SOD and CAT were significantly lower after high-dose compared to low-dose administration of RES (P<.03 and P<.01). In conclusion, in healthy subjects, neither 0.05g nor 5g RES changed blood oxidative state, although our in vitro data point to a prooxidative activity of low concentrations of RES and its metabolites, which could be important in vivo for individuals with compromised antioxidant defense capacity

Stromal and therapy-induced macrophage proliferation promotes PDAC progression and susceptibility to innate immunotherapy

Tumor-associated macrophages (TAMs) are abundant in pancreatic ductal adenocarcinomas (PDACs). While TAMs are known to proliferate in cancer tissues, the impact of this on macrophage phenotype and disease progression is poorly understood. We showed that in PDAC, proliferation of TAMs could be driven by colony stimulating factor-1 (CSF1) produced by cancer-associated fibroblasts. CSF1 induced high levels of p21 in macrophages, which regulated both TAM proliferation and phenotype. TAMs in human and mouse PDACs with high levels of p21 had more inflammatory and immunosuppressive phenotypes. p21 expression in TAMs was induced by both stromal interaction and/or chemotherapy treatment. Finally, by modeling p21 expression levels in TAMs, we found that p21-driven macrophage immunosuppression in vivo drove tumor progression. Serendipitously, the same p21-driven pathways that drive tumor progression also drove response to CD40 agonist. These data suggest that stromal or therapy-induced regulation of cell cycle machinery can regulate both macrophage-mediated immune suppression and susceptibility to innate immunotherapy

Mediterranean Diet and Breast Density in the Minnesota Breast Cancer Family Study

Mediterranean populations’ lower breast cancer incidence has been attributed to a traditional Mediterranean diet, but few studies have quantified Mediterranean dietary pattern intake in relation to breast cancer. We examined the association of a Mediterranean diet scale (MDS) with mammographic breast density as a surrogate marker for breast cancer risk. Participants completed a dietary questionnaire and provided screening mammograms for breast density assessment using a computer-assisted method. Among 1,286 women, MDS was not clearly associated with percent density in multivariate linear regression analyses. Because of previous work suggesting dietary effects limited to smokers, we conducted stratified analyses and found MDS and percent density to be significantly, inversely associated among current smokers (β = –1.68, P = 0.002) but not among nonsmokers (β = –0.08, P = 0.72; P for interaction = 0.008). Our results confirm a previous suggestion that selected dietary patterns may be protective primarily in the presence of procarcinogenic compounds such as those found in tobacco smoke

Preventive effects of dietary hydroxytyrosol acetate, an extra virgin olive oil polyphenol in murine collagen-induced arthritis

Scope: Hydroxytyrosol acetate (HTy-Ac), an extra virgin olive oil (EVOO) polyphenol, has recently been reported to exhibit antioxidant and anti-inflammatory effects on LPS-stimulated macrophagesand ulcerative colitis. This study was designed to evaluate dietary HTy-Ac supplementation effects on collagen-induced arthritis (CIA) in mice. Methods and results: DBA-1/J mice were fed from weaning with 0.05% HTy-Ac. After 6 weeks, arthritis was induced by type II collagen. Mice were sacrificed 42 days after first immunization. Blood was recollected and paws were histological and biochemically processed. HTy-Ac diet significantly prevent edarthritis development and decreased serum IgG1 and IgG2a, cartilage olimeric matrix protein (COMP) and metalloproteinase-3 (MMP-3) levels, as well as, pro-inflammatory cytokines levels (TNF-alpha, IFN-gamma, IL-1 beta, IL-6 and IL-17A). The activation of Janus kinase-signal transducer and activator of transcription (JAK/STAT), mitogen-activated protein kinases (MAPKs) and nuclear transcription factor-kappa B (NF-kappa B) pathways were drastically ameliorated whereas nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) protein expressions were significantly up-regulated in those mice fed with HTy-Ac. Conclusion: HTy-Ac improved the oxidative events and returned pro-inflammatory proteins expression to basal levels probably through JAK/STAT, MAPKs and NF-kappa B pathways. HTy-Ac supplement might provide a basis for developing a new dietary strategy for the prevention of rheumatoid arthritis

Tissue Engineering Scaffolds Fabricated in Dissolvable 3D-Printed Molds for Patient-Specific Craniofacial Bone Regeneration

The current gold standard treatment for oral clefts is autologous bone grafting. This treatment, however, presents another wound site for the patient, greater discomfort, and pediatric patients have less bone mass for bone grafting. A potential alternative treatment is the use of tissue engineered scaffolds. Hydrogels are well characterized nanoporous scaffolds and cryogels are mechanically durable, macroporous, sponge-like scaffolds. However, there has been limited research on these scaffolds for cleft craniofacial defects. 3D-printed molds can be combined with cryogel/hydrogel fabrication to create patient-specific tissue engineered scaffolds. By combining 3D-printing technology and scaffold fabrication, we were able to create scaffolds with the geometry of three cleft craniofacial defects. The scaffolds were then characterized to assess the effect of the mold on their physical properties. While the scaffolds were able to completely fill the mold, creating the desired geometry, the overall volumes were smaller than expected. The cryogels possessed porosities ranging from 79.7% to 87.2% and high interconnectivity. Additionally, the cryogels swelled from 400% to almost 1500% of their original dry weight while the hydrogel swelling did not reach 500%, demonstrating the ability to fill a defect site. Overall, despite the complex geometry, the cryogel scaffolds displayed ideal properties for bone reconstruction

Essential oil of Dittrichia viscosa ssp. viscosa: analysis by 13C-NMR and antimicrobial activity

The essential oil of Dittrichia viscosa ssp. viscosa from Corsica was investigated by GC and 13C-NMR spectroscopy. First, the sample was submitted to an acido-basic partition and the neutral part was repeatedly chromatographed. The analysis of all the fractions led to the identification of 71 components. The main constituents were fokienol (21.1%), (E)-nerolidol (8.6%) and eudesm-6-en-4alpha-ol (6.2%). The antimicrobial activity of the neutral and acidic fractions were investigated. While the neutral part appeared to be inactive, the acidic part was active against all the tested microorganisms. The highest activity was obtained against Staphylococcus epidermidis, Streptococcus foecalis and Proteus vulgaris. Copyright © 2005 John Wiley & Sons, Ltd