Complex Electrograms Within the Coronary Sinus: Time- and Frequency-Domain Characteristics, Effects of Antral Pulmonary Vein Isolation, and Relationship to Clinical Outcome in Patients with Paroxysmal and Persistent Atrial Fibrillation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73243/1/j.1540-8167.2008.01175.x.pd

Cytochrome P450-derived epoxyeicosatrienoic acids and coronary artery disease in humans: a targeted metabolomics study

Cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) exhibit potent cardiovascular protective effects in preclinical models, and promoting the effects of EETs has emerged as a potential therapeutic strategy for coronary artery disease (CAD). The relationship between circulating EET levels and CAD extent in humans, however, remains unknown. A panel of free (unesterified) plasma eicosanoid metabolites was quantified in 162 patients referred for coronary angiography, and associations with extent of CAD [no apparent CAD (N = 39), nonobstructive CAD (N = 51), and obstructive CAD (N = 72)] were evaluated. A significant relationship between free EET levels and CAD extent was observed (P = 0.003) such that the presence of obstructive CAD was associated with lower circulating EET levels. This relationship was confirmed in multiple regression analysis where CAD extent was inversely and significantly associated with EET levels (P = 0.013), and with a biomarker of EET biosynthesis (P < 0.001), independent of clinical and demographic factors. Furthermore, quantitative enrichment analysis revealed that these associations were the most pronounced compared with other eicosanoid metabolism pathways. Collectively, these findings suggest that the presence of obstructive CAD is associated with lower EET metabolite levels secondary to suppressed EET biosynthesis. Novel strategies that promote the effects of EETs may have therapeutic promise for patients with obstructive CAD

Characterization of the Cytochrome P450 epoxyeicosanoid pathway in non-alcoholic steatohepatitis

Non-alcoholic steatohepatitis (NASH) is an emerging public health problem without effective therapies. Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into bioactive epoxyeicosatrienoic acids (EETs), which have potent anti-inflammatory and protective effects. However, the functional relevance of the CYP epoxyeicosanoid metabolism pathway in the pathogenesis of NASH remains poorly understood. Our studies demonstrate that both mice with methionine-choline deficient (MCD) diet-induced NASH and humans with biopsy-confirmed NASH exhibited significantly higher free EET concentrations compared to healthy controls. Targeted disruption of Ephx2 (the gene encoding for soluble epoxide hydrolase) in mice further increased EET levels and significantly attenuated MCD diet-induced hepatic steatosis, inflammation and injury, as well as high fat diet-induced adipose tissue inflammation, systemic glucose intolerance and hepatic steatosis. Collectively, these findings suggest that dysregulation of the CYP epoxyeicosanoid pathway is a key pathological consequence of NASH in vivo, and promoting the anti-inflammatory and protective effects of EETs warrants further investigation as a novel therapeutic strategy for NASH

Microarray analysis of mRNA from cumulus cells following in vivo or in vitro maturation of mouse cumulus-oocyte complexes

The IVM of mammalian cumulus–oocyte complexes (COCs) yields reduced oocyte developmental competence compared with oocytes matured in vivo. Altered cumulus cell function during IVM is implicated as one cause for this difference. We have conducted a microarray analysis of cumulus cell mRNA following IVM or in vivo maturation (IVV). Mouse COCs were sourced from ovaries of 21-day-old CBAB6F1 mice 46 h after equine chorionic gonadotrophin (5 IU, i.p.) or from oviducts following treatment with 5 IU eCG (61 h) and 5 IU human chorionic gonadotrophin (13 h). IVM was performed in α-Minimal Essential Medium with 50 mIU FSH for 17 h. Three independent RNA samples were assessed using the Affymetrix Gene Chip Mouse Genome 430 2.0 array (Affymetrix, Santa Clara, CA, USA). In total, 1593 genes were differentially expressed, with 811 genes upregulated and 782 genes downregulated in IVM compared with IVV cumulus cells; selected genes were validated by real-time reverse transcription–polymerase chain reaction (RT-PCR). Surprisingly, haemoglobin α (Hba-a1) was highly expressed in IVV relative to IVM cumulus cells, which was verified by both RT-PCR and western blot analysis. Because haemoglobin regulates O2 and/or nitric oxide availability, we postulate that it may contribute to regulation of these gases during the ovulatory period in vivo. These data will provide a useful resource to determine differences in cumulus cell function that are possibly linked to oocyte competence.Karen L. Kind, Kelly M. Banwell, Kathryn M. Gebhardt, Anne Macpherson, Ashley Gauld, Darryl L. Russell and Jeremy G. Thompso

Some reactions of tris(trimethylstannyl)- and tetrakis(trimethylstannyl)-methane

With a variety of electrophilic reagents reaction occurs exclusively at the CHSn bonds of [(CH)Sn]C and [(CH)Sn]CH. While the inner SnC bonds remain intact, methyl groups may be progressively cleaved off, one from each of the trimethylstannyl groups; in the case of bromine a second Me group may be cleaved from each of the SnMeBr groups. The various products were identified by H, C and Sn NMR spectroscopy

Faculty Recital, Dr. Darryl Harper, jazz clarinet

Second Half of Performance Y\u27all Got It: Music from The Wiz by Charlie Small

Rates of Oral Anticoagulant Use in Patients With Atrial Fibrillation Managed By Primary Care and Cardiology Providers With or Without Use of a Structured Note For Pinnacle Registry Reporting

Background Oral anticoagulant (OAC) therapy is underutilized in patients with atrial fibrillation (AF) and a CHA2DS2-VASc score ≥2. However, the patterns of OAC selection, adherence with recommendations, and impact of structured note reporting among different specialties has not been well described. Methods As a part of an internal Quality Improvement initiative, records at Swedish Medical Center (Seattle, WA) from 2016 were reviewed. 10,928 patients had a diagnosis of AF. 3362 were seen by a Primary Care Provider (PCP) and not cardiology, 4439 were seen by cardiology and not a PCP, and 3127 seen by both PCP and cardiology. Rates of discrete reporting of the CHA2DS2-VASc score were noted and for those with a CHA2DS2-VASc score \u3e2, overall use, and specific use of Direct Oral Anticoagulant (DOAC), warfarin, antiplatelet alone, or no therapy was tabulated. Individual provider data for the 8 cardiology providers routinely using the PINNACLE Note were tabulated, and also adjusted for why not given codes. Results Of the overall PCP patients (N=6489), 1862 (29%) had a CHA2DS2-VASc score, and 1552 (24%) had a CHA2DS2-VASc score ≥2. Of the overall cardiology patients (N= 7566), 4261 (56%) had a CHA2DS2-Vasc score documented, and of those, 3517 (46%) had a CHA2DS2-Vasc score ≥2. Of the PCP patients with a CHA2DS2-Vasc of ≥2, 35% were treated with warfarin, 36% were treated with a DOAC, 29% with an antiplatelet, and 19% were not treated. Of the cardiology patients, 31% were treated with warfarin, 38% with DOAC, 27% with an antiplatelet, and 23% were not treated. Among the PINNACLE note providers, overall adherence with recommendations was 75%, but after adjusting for why not given codes, adherence was 95% (p \u3c0.05). Conclusion CHA2DS2-Vasc scores are inconsistently documented by both PCP and cardiology providers. Among patients with documented CHA2DS2-Vasc scores of ≥2, 19% of PCP patients and 23% of cardiology patients did not have documented anticoagulation. DOAC use was more prevalent among cardiologists. Of the providers using the PINNACLE Note, following adjustment for why not given codes, documentation of adherence with guideline recommended treatment was 95%