Malondialdehyde Acetaldehyde Adducts (MAA-Adducts) Direct Distinctive Pro-Inflammatory Responses in Endothelial and Macrophage Cell Lines

Chronic inflammation plays a critical role in the pathogenesis of atherosclerosis. At present, the mechanism(s) by which inflammation contributes to this disease isnot entirely understood. Inflammation is known to induce oxidative stress, of which one consequence is lipid peroxidation. This process leads to the production of malondialdehyde (MDA), which can subsequently break down to form acetaldehyde (AA). These two aldehyde by-products can covalently interact with the ε-amino group of lysineswithin proteins and lipoproteins leading to the formation of highly immunogenic malondialdehyde-acetaldehyde adducts (MAA-adducts). The aim of this study was to determine the in-vitro cytokine response of endothelial cells and macrophages treated with MAA-modified human serum albumin (HSA-MAA) and low-density lipoprotein (LDL-MAA). In addition, cells isolated from mice with exposure to MAA and high fat diets were stained and imaged for uptake of the modified macromolecules of interest. We found that exposure of endothelial cells resulted in increased expression of IL-6, TNF-α, ICAM-1, VCAM-1, and MCP-1 in response to incubation with HSA-MAA; whereas, the same treatment of macrophages resulted in increased expression of IL-6, TNF-α, and IL-1b. LDL-MAA incubationresulted in increased TNF-α expression in macrophages, but MCP-1 was elevated in endothelial cells. Interestingly, the quantitative and qualitative uptake of triglycerides was increased in both endothelial and macrophage cells when exposed to LDL-MAA compared to LDL alone. The results of these studies demonstrate that different MAA-adducts elicit unique responses in different cell types. Additionally, the presence of MAA appears to modulate the cells leading to increased uptake of triglycerides and further progression of the inflammatory response.https://digitalcommons.unmc.edu/emet_posters/1003/thumbnail.jp

Novel Antioxidant Properties of Doxycycline

Doxycycline (DOX), a derivative of tetracycline, is a broad-spectrum antibiotic that exhibits a number of therapeutic activities in addition to its antibacterial properties. For example, DOX has been used in the management of a number of diseases characterized by chronic inflammation. One potential mechanism by which DOX inhibits the progression of these diseases is by reducing oxidative stress, thereby inhibiting subsequent lipid peroxidation and inflammatory responses. Herein, we tested the hypothesis that DOX directly scavenges reactive oxygen species (ROS) and inhibits the formation of redox-mediated malondialdehyde-acetaldehyde (MAA) protein adducts. Using a cell-free system, we demonstrated that DOX scavenged reactive oxygen species (ROS) produced during the formation of MAA-adducts and inhibits the formation of MAA-protein adducts. To determine whether DOX scavenges specific ROS, we examined the ability of DOX to directly scavenge superoxide and hydrogen peroxide. Using electron paramagnetic resonance (EPR) spectroscopy, we found that DOX directly scavenged superoxide, but not hydrogen peroxide. Additionally, we found that DOX inhibits MAA-induced activation of Nrf2, a redox-sensitive transcription factor. Together, these findings demonstrate the under-recognized direct antioxidant property of DOX that may help to explain its therapeutic potential in the treatment of conditions characterized by chronic inflammation and increased oxidative stress

Direct antioxidant properties of methotrexate: Inhibition of malondialdehyde-acetaldehyde-protein adduct formation and superoxide scavenging.

Methotrexate (MTX) is an immunosuppressant commonly used for the treatment of autoimmune diseases. Recent observations have shown that patients treated with MTX also exhibit a reduced risk for the development of cardiovascular disease (CVD). Although MTX reduces systemic inflammation and tissue damage, the mechanisms by which MTX exerts these beneficial effects are not entirely known. We have previously demonstrated that protein adducts formed by the interaction of malondialdehyde (MDA) and acetaldehyde (AA), known as MAA-protein adducts, are present in diseased tissues of individuals with rheumatoid arthritis (RA) or CVD. In previously reported studies, MAA-adducts were shown to be highly immunogenic, supporting the concept that MAA-adducts not only serve as markers of oxidative stress but may have a direct role in the pathogenesis of inflammatory diseases. Because MAA-adducts are commonly detected in diseased tissues and are proposed to mitigate disease progression in both RA and CVD, we tested the hypothesis that MTX inhibits the generation of MAA-protein adducts by scavenging reactive oxygen species. Using a cell free system, we found that MTX reduces MAA-adduct formation by approximately 6-fold, and scavenges free radicals produced during MAA-adduct formation. Further investigation revealed that MTX directly scavenges superoxide, but not hydrogen peroxide. Additionally, using the Nrf2/ARE luciferase reporter cell line, which responds to intracellular redox changes, we observed that MTX inhibits the activation of Nrf2 in cells treated with MDA and AA. These studies define previously unrecognized mechanisms by which MTX can reduce inflammation and subsequent tissue damage, namely, scavenging free radicals, reducing oxidative stress, and inhibiting MAA-adduct formation

Public awareness and support for use of wastewater for SARS-CoV-2 monitoring: A community survey in Louisville, Kentucky

The majority of sewer systems in the United States and other countries, are operated by public utilities. In the absence of any regulation, public perception of monitoring wastewater for population health biomarkers is an important consideration for a public utility commission when allocating resources for this purpose. In August 2021, we conducted a survey as part of an ongoing COVID-19 community prevalence study in Louisville/Jefferson County, KY. The survey comprised of seven questions about awareness of and privacy concerns and was sent to 32,000 households randomly distributed within the county. A total of 1,220 sampled adults participated in the probability sample, and 981 were used in analysis. A total of 2,444 adults additionally responded in the convenience sample, and 1,751 were used in analysis. The samples were weighted to produce estimates representative of all adults in the county. Public awareness of tracking COVID-19 virus in the sewers was low. Opinions about how data from this activity are shared strongly supported public disclosure of monitoring results. Responses showed more support for measuring the largest areas (\u3e30,000 to 50,000 households) typically representing population levels found in a community or regional wastewater treatment plant. Those who had a history of COVID-19 infection were more likely to support highly localized monitoring. Understanding wastewater surveillance strategies and thresholds of privacy concerns requires in-depth, comprehensive analysis of public opinion for continued success and efficacy of public health monitoring

Language, Religion, and Ethnic Civil War

Are certain ethnic cleavages more conflict-prone than others? While only few scholars focus on the contents of ethnicity, most of those who do argue that political violence is more likely to occur along religious divisions than linguistic ones. We challenge this claim by analyzing the path from linguistic differences to ethnic civil war along three theoretical steps: (1) the perception of grievances by group members, (2) rebel mobilization, and (3) government accommodation of rebel demands. Our argument is tested with a new data set of ethnic cleavages that records multiple linguistic and religious segments for ethnic groups from 1946 to 2009. Adopting a relational perspective, we assess ethnic differences between potential challengers and the politically dominant group in each country. Our findings indicate that intrastate conflict is more likely within linguistic dyads than among religious ones. Moreover, we find no support for the thesis that Muslim groups are particularly conflict-prone

Crop Updates 2000 Cereals - part 3

This session covers eighteen papers from different authors: BARLEY AND OAT AGRONOMY 1. Unicorn barley must meet malting specifications to be a viable option, Roslyn Jettnerand Blakely Paynter, Agriculture Western Australia 2. Optimum oat seed rates, Glenn McDonald, Agriculture Western Australia 3. Production and Quality of export Oaten Hay (1998 and 1989), Pierre Fievez, Pierre Fievez and Associates FROST 4. Climatology of Frost in Southern Western Australia, Ian Foster, Agriculture Western Australia 5. Flowering calculator, David Tennant, Agriculture Western Australia 6. Some options for managing the risk of frost damage, Wal Anderson, Agriculture Western Australia PASTURE 7. TIMERITE® Control of redlegged earth mite in south western Australia with a spring spray to pastures, James Ridsdill-Smith and Celia Pavri, CSIRO Entomology, University of Western Australia 8. The pattern of seed softening in subterranean clover in relation to presicted false break risk, Ross Chapman and Senthold Asseng, CSIRO Plant Industry, Centre for Mediterranean Agricultural Research 9. Charano serradella – a viable option for 1:1 cropping, Steve Carr and Brad Nutt IAMA Agri-Services Western Australia and Centre for Legumes in Mediterranean Agriculture, University of Western Australia 10. Alfalfa mosaic virus in alternative annual pasture and forage legumes, Lindrea Latham and Roger Jones, Crop Improvement Institute, Agriculture Western Australia and Centre for Legumes in Mediterranean Agriculture, University of Western Australia 11. Pasture mixture performs better than single-species-based pasture – 1999, Anyou Liu, Clinton Revell and David Ferris, Centre for Cropping Systems, Agriculture Western Australia 12. Better pasture management improves performance of following crops – 1999, Anyou Liu, Clinton Revell and David Ferris, Centre for Cropping Systems, Agriculture Western Australia 13. Lucerne Benefits Crop Production, Roy Latta1, Lisa-Jane Blacklow2, Chris Matthews1 1Agriculture Western Australia 2University of Western Australia 14. Does size count? Determining optimum release number of red apion for biocontrol of doublegee, Tim Woodburn and Paul Yeoh, CSIRO Entomology/CRC Weed Management Systems, Perth 15. Herbicide tolerance of some new cultivars of annual pasture legumes, Clinton Revell and Ian Rose, Centre for Cropping Systems, Agriculture Western Australia 16. Lucerne – crop rotations in the Esperance region, Anita Lyons, Roy Latta and Chris Matthews,Agriculture Western Australia PRECISION AGRICULTURE 17. Assessing the results of on-farm experiments using yield monitors, Simon Cook and Matthew Adams, CSIRO Land and Water 18. Achiever: A GIS based achievable yield and fertiliser recommendation system for precision agriculture, Robert J. Corner, Matthew L. Adams, Precision Agriculture Research Group CSIRO Land and Wate

What rheumatologists in the United States think of complementary and alternative medicine: results of a national survey

<p>Abstract</p> <p>Background</p> <p>We aimed to describe prevailing attitudes and practices of rheumatologists in the United States toward complementary and alternative medicine (CAM) treatments. We wanted to determine whether rheumatologists' perceptions of the efficacy of CAM therapies and their willingness to recommend them relate to their demographic characteristics, geographic location, or clinical practices.</p> <p>Methods</p> <p>A National Institutes of Health-sponsored cross-sectional survey of internists and rheumatologists was conducted regarding CAM for treatment of chronic back pain or joint pain. In this study we analyzed responses only from rheumatologists. Response items included participant characteristics and experience with 6 common CAM categories, as defined by the National Institutes of Health. Descriptive statistics were used to describe attitudes to CAM overall and to each CAM category. Composite responses were devised for respondents designating 4 or more of the 6 CAM therapies as "very" or "moderately" beneficial or "very likely" or "somewhat likely" to recommend.</p> <p>Results</p> <p>Of 600 rheumatologists who were sent the questionnaire, 345 responded (58%); 80 (23%) were women. Body work had the highest perceived benefit, with 70% of respondents indicating benefit. Acupuncture was perceived as beneficial by 54%. Most were willing to recommend most forms of CAM. Women had significantly higher composite benefit and recommend responses than men. Rheumatologists not born in North America were more likely to perceive benefit of select CAM therapies.</p> <p>Conclusions</p> <p>In this national survey of rheumatologists practicing in the United States, we found widespread favorable opinion toward many, but not all, types of CAM. Further research is required to determine to what extent CAM can or should be integrated into the practice of rheumatology in the United States.</p