Mass Spectrometric Analysis of Oxidized Eicosapentaenoic Acid Sodium Salt

Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid (PUFA) with 20 carbon atoms and 5 carbon-carbon double bonds. Mammalian cells cannot synthesize long chain PUFAs such as EPA de novo, and, thus, the most effective way to enrich cells in EPA is by dietary intake of fish oils. EPA supplementation causes an increase in its concentration in plasma lipids and in cell membrane phospholipids. Many beneficial effects of EPA supplementation have been noted, including (1) the potential to sensitize cancerous tumors towards chemotherapy, (2) the promotion of cardiovascular health, and (3) the alleviation of some mental disorders, but results from clinical trials have sometimes been disparate. In this study, we report the use of mass spectrometry to investigate the autoxidation of EPA, thereby demonstrating the formation of a variety of oxidized products. The oxidative stress of the patient may affect the response to EPA and may, in part, explain divergent results from clinical trials

Mass Spectrometric Analysis of Oxidized Eicosapentaenoic Acid Sodium Salt

Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid (PUFA) with 20 carbon atoms and 5 carbon-carbon double bonds. Mammalian cells cannot synthesize long chain PUFAs such as EPA de novo, and, thus, the most effective way to enrich cells in EPA is by dietary intake of fish oils. EPA supplementation causes an increase in its concentration in plasma lipids and in cell membrane phospholipids. Many beneficial effects of EPA supplementation have been noted, including (1) the potential to sensitize cancerous tumors towards chemotherapy, (2) the promotion of cardiovascular health, and (3) the alleviation of some mental disorders, but results from clinical trials have sometimes been disparate. In this study, we report the use of mass spectrometry to investigate the autoxidation of EPA, thereby demonstrating the formation of a variety of oxidized products. The oxidative stress of the patient may affect the response to EPA and may, in part, explain divergent results from clinical trials

Eicosapentaenoic Acid Modulates Trichomonas 1 vaginalis Activity

Trichomonas vaginalis is a sexually transmitted parasite and, while it is often asymptomatic in 50 males, the parasite is associated with disease in both sexes. Metronidazole is an effective 51 treatment for trichomoniasis, but resistant strains have evolved and, thus, it has become 52 necessary to investigate other possible therapies. In this study, we examined the effects of native 53 and oxidized forms of the sodium salts of eicosapentaenoic, docosahexaenoic and arachidonic 54 acids on T. vaginalis activity. Eicosapentaenoic acid was the most toxic with 190 μM and 380 55 μM causing approximately 90% cell death in Casu2 and ATCC 50142 strains, respectively. In 56 contrast, oxidized eicosapentaenoic acid was the least toxic, requiring \u3e3 mM to inhibit activity, 57 while low levels (10μM) were associated with increased parasite density. Mass spectrometric 58 analysis of oxidized eicosapentaenoic acid revealed C20 products containing one to six 59 additional oxygen atoms and various degrees of bond saturation. These results indicate that 60 eicosapentaenoic acid has different effects on T. vaginalis survival, depending on whether it is 61 present in the native or oxidized form. A better understanding of lipid metabolism in T. vaginalis 62 may facilitate the design of synthetic fatty acids that are effective for the treatment of 63 metronidazole-resistant T. vaginalis

An exploratory survey on the awareness and usage of clinical practice guidelines among clinical pharmacists

Background: The NHLBI has not developed clinical practice guidelines since 2007. As a result, multiple organizations have released competing guidelines. This has created confusion and debate among clinicians as to which recommendations are most applicable for practice. Objectives: To explore preliminary attitudes, awareness, and usage of clinical practice guidelines in practice and teaching for hypertension, dyslipidemia and asthma among clinical pharmacists. Methods: Clinical pharmacists across the US were surveyed electronically over a two week period in Spring 2019 regarding utilization and knowledge of practice guidelines for hypertension, dyslipidemia, and asthma. Clinical cases were included to evaluate application of guidelines. Descriptive statistics, Chi-square analysis, and Wilcoxon signed-rank test were conducted. Statistical significance level was set to 0.01 to account for multiple tests conducted on the same survey participants. Results: Forty-eight, 34, and 28 pharmacists voluntarily completed hypertension, dyslipidemia, and asthma survey questions, respectively. Interactions by disease state (p \u3c 0.001) revealed more pharmacists (93%) reporting to have ≤50% patient load in managing asthma and more pharmacists (95%) had read the full summary/report of the most recent hypertension guideline. Primary reasons why the most recent guideline was not selected were also significantly different by disease state (interaction; p \u3c 0.001). For dyslipidemia and asthma, pharmacists had a higher mean rating of agreement (p \u3c0.007) in having the most confidence in the most recent as compared to older guidelines. Proportionally more clinical cases were answered correctly (interaction; p \u3c0.001) when pharmacists applied the most recent guideline for hypertension (84%), while the opposite outcome was found for asthma (27%). Conclusion: While more pharmacists selected the most recent guideline for practice and teaching, there was inconsistent application of guidelines to clinical cases. Further studies with a larger representation of pharmacists are warranted to more definitively determine factors influencing guideline preference and usage

Analysis of Sex-Specific Prostanoid Production Using a Mouse Model of Selective Cyclooxygenase-2 Inhibition

Background: Prostanoids are a family of lipid mediators formed from arachidonic acid by cyclooxygenase enzymes and serve as biomarkers of vascular function. Prostanoid production may be different in males and females indicating that different therapeutic approaches may be required during disease. Objecti ves: We examined sex-dependent differences in COX-related metabolites in genetically modified mice that produce a cyclooxygenase- 2 (COX2) enzyme containing a tyrosine 385 to phenylalanine (Y385F) mutation. This mutation renders the COX2 enzyme unable to form a key intermediate radical required for complete arachidonic acid metabolism and provides a model of selective COX2 inhibition. Design and Methods: Mice heterozygous for the Y385F mutation in COX2 were mated to produce cohorts of wild-type, heterozygous, and COX2 mutant mice. We investigated whether the genotype distribution followed Mendelian genetics and studied whether sex-specific differences could be found in certain prostanoid levels measured in peritoneal macrophages and in urinary samples. Results : The inheritance of the COX2 mutation displayed a significant deviation with respect to Mendel’s laws of genetics, with a lowerthan- expected progeny of weaned COX2 mutant pups. In macrophages, prostaglandin E2 (PGE2) production following lipopolysaccharide (LPS) and interferon gamma (IFNγ) stimulation was COX2-dependent in both males and females, and data indicated that crosstalk between the nitric oxide (NO) and COX2 pathways may be sex specific. We observed significant differences in urinary PGE2 production by male and female COX2 mutant mice, with the loss of COX2 activity in male mice decreasing their ability to produce urinary PGE2. Finally, female mice across all 3 genotypes produced similar levels of urinary thromboxane (measured as 11-dehydro TxB2) at significantly higher levels than males, indicating a sex-related difference that is likely COX1-derived. Conclusions: Our findings clearly demonstrate that sex-related differences in COX-derived metabolites can be observed, and that other pathways (such as the NO pathway) are affected

Concert recording 2019-04-16

[Track 1]. Rotation #2 / Eric Sammut -- [Track 2]. Pines of Rome mvt 1 / Ottorino Respighi -- [Track 3]. Chart #2 / Fernando Valencia -- [Track 4]. Chopstakovich / Jesse Sieff -- [Track 5]. Drei Skizzen mvt. III / Matthias Schmitt -- [Track 6]. Sonata no. 1 for G in violoncello. Prelude [Track 7]. Sarabande [Track 8]. Courante / J.S. Bach -- [Track 9]. #1 from Douze Etudes / Jacques Delecluse -- [Track 10]. The offering / Michael Burritt -- [Track 11]. Prelude and blues / Ney Rosauro -- [Track 12]. Danny boy / traditional arranged by Brian Mueller -- [Track 13]. Ransom / Mark Ford -- [Track 14]. Sonata for timpani mvt III / John Beck -- [Track 15]. Dr. Gradus ad Parnassum / Claude Debussy arranged by Paul Bissell -- [Track 16]. Etude #1 / Vic Firth -- [Track 17]. Highlights from Northern lights / Eric Ewazen -- [Track 18]. Jesus loves me / Chad Floyd -- [Track 19]. Faded lines / Andrea Venet - [Track 20]. Triplets / George Hamilton Green arranged by Bob Becker -- [Track 21]. Girlfriends medley / Bob Becker -- [Track 22]. Selections from Oru Secu. Guaguancó [Track 23]. Guarapachangueo / Traditional trans. Valencia

A Measurement of the Interference Structure Function, R_LT, for the 12C(e,e'p) reaction in the Quasielastic Region

The coincidence cross-section and the interference structure function, R_LT, were measured for the 12C(e,e'p) 11B reaction at quasielastic kinematics and central momentum transfer of q=400 MeV/c. The measurement was at an opening angle of theta_pq=11 degrees, covering a range in missing energy of E_m = 0 to 65 MeV. The R_LT structure function is found to be consistent with zero for E_m > 50 MeV, confirming an earlier study which indicated that R_L vanishes in this region. The integrated strengths of the p- and s-shell are compared with a Distorted Wave Impulse Approximation calculation. The s-shell strength and shape are compared with a Hartree Fock-Random Phase Approximation calculation. The DWIA calculation overestimates the cross sections for p- and s-shell proton knockout as expected, but surprisingly agrees with the extracted R_LT value for both shells. The HF-RPA calculation describes the data more consistently, which may be due to the inclusion of 2-body currents in this calculation.Comment: 8 Pages LaTex, 5 postscript figures. Submitted to Phys. Rev.

YAP and TAZ Mediate Osteocyte Perilacunar/Canalicular Remodeling

Bone fragility fractures are caused by low bone mass or impaired bone quality. Osteoblast/osteoclast coordination determines bone mass, but the factors that control bone quality are poorly understood. Osteocytes regulate osteoblast and osteoclast activity on bone surfaces but can also directly reorganize the bone matrix to improve bone quality through perilacunar/canalicular remodeling; however, the molecular mechanisms remain unclear. We previously found that deleting the transcriptional regulators Yes-associated protein (YAP) and Transcriptional co-activator with PDZ-motif (TAZ) from osteoblast-lineage cells caused lethality in mice due to skeletal fragility. Here, we tested the hypothesis that YAP and TAZ regulate osteocyte-mediated bone remodeling by conditional ablation of both YAP and TAZ from mouse osteocytes using 8kb-DMP1-Cre. Osteocyte-conditional YAP/TAZ deletion reduced bone mass and dysregulated matrix collagen content and organization, which together decreased bone mechanical properties. Further, YAP/TAZ deletion impaired osteocyte perilacunar/canalicular remodeling by reducing canalicular network density, length, and branching, as well as perilacunar flourochrome-labeled mineral deposition. Consistent with recent studies identifying TGF-β as a key inducer of osteocyte expression of matrix-remodeling enzymes, YAP/TAZ deletion in vivo decreased osteocyte expression of matrix proteases MMP13, MMP14, and CTSK. In vitro, pharmacologic inhibition of YAP/TAZ transcriptional activity in osteocyte-like cells abrogated TGF-β-induced matrix protease gene expression. Together, these data show that YAP and TAZ control bone matrix accrual, organization, and mechanical properties by regulating osteocyte-mediated bone remodeling. Elucidating the signaling pathways that control perilacunar/canalicular remodeling may enable future therapeutic targeting of bone quality to reverse skeletal fragility