Abstract 14456: Rethinking The Treatment Of Cardiac Arrest To Include Non-oxygen Metabolite Supplementation: Plasma Lysophosphatidylcholine Level Maintenance After Cardiac Arrest Is Critical For Survival

Cardiac arrest (CA) is a loss of circulation that curtails the supply of oxygen and non-oxygen metabolites to the whole body resulting in ischemia and death. Subsequent resuscitation is vital for survival, but also causes reperfusion injury. Oxygen deprivation as one arm of ischemia-reperfusion injury and its relationship with death is well-established, but its counterpart, metabolite dysfunction, is overlooked and poorly understood. We have previously shown that many metabolites are not normalized as efficiently or rapidly after resuscitation especially, particularly those that are severely decreased after CA. As such, we hypothesize that appropriate replenishment of certain metabolites is essential for survival. Lysophosphatidylcholine (LPC), an important family of phospholipids, is an example of such non-oxygen metabolites required post-CA. With multifactorial roles for maintaining homeostasis, such as acting as an energy substrate, maintaining membrane integrity, and functioning in inter- and intra-cellular signaling, decreased levels of LPC post-CA disrupts the various physiologic responsibilities resulting in profound systemic effects causing cellular and organ system injury. In this analysis, 1) phospholipid screening using HPLS-MS on plasma samples obtained from asphyxial-CA rats and human CA patients shows that LPC significantly decreases post-CA, especially during the reperfusion phase, and is strongly correlated with the duration of preceding CA and poor neurological/survival outcomes, and 2) individual supplementation of three species of LPC (LPC 18:0, LPC 18:1, and LPC 22:6) following resuscitation after 10 and 12 min rat CA helps improve survival and brain function as compared with vehicle. Overall, our study highlights that LPC is an essential, non-oxygen metabolite that is necessary to help promote survival after CA in rats that has therapeutic potential for human translation.

Energy expenditure across immune challenge severities in a lizard: consequences for innate immunity, locomotor performance, and oxidative status

Reptiles, like other vertebrates, rely on immunity to defend themselves from infection. The energetic cost of an immune response is liable to scale with infection severity, prompting constraints on other self-maintenance traits if immune prioritization exceeds energy budget. In this study, adult male side-blotched lizards (Uta stansburiana) were injected with high (20 µg/g body mass), low (10 µg/g body mass), or control (0 µg/g body mass) concentrations of lipopolysaccharide (LPS) to simulate bacterial infections of discrete severities. The costs and consequences of the immune response were assessed through comparisons of change in resting metabolic rates (RMR), energy metabolites (glucose, glycerol, triglycerides), innate immunity (bactericidal ability), sprint speed changes, and oxidative status (antioxidant capacity, reactive oxygen metabolites). High-LPS lizards had the lowest glucose levels and greatest sprint reductions, while their RMR and bactericidal ability were similar to control lizards. Low-LPS lizards had elevated RMR and bactericidal ability, but glucose levels and sprint speed changes between that of high-LPS and control lizards. Levels of glycerol, triglycerides, reactive oxygen metabolites, and antioxidant capacity did not differ by treatment. Taken together, energy expenditure for the immune response differentially varies with challenge severity, posing consequences for self-maintenance processes in a reptile.

Effects of Non-Surgical Periodontal Treatment on Reactive Oxygen Metabolites and Glycemic Control in Diabetic Patients with Chronic Periodontitis

Background: Periodontal infection may contribute to poor glycemic control and systemic inflammation in diabetic patients. The aim of the present study is to evaluate the efficacy of non-surgical periodontal treatment in diabetic patients by measuring oxidative stress outcomes. Methods: Sixty diabetic patients with periodontitis were enrolled, treated with scaling and full-mouth disinfection, and randomly prescribed chlorhexidine mouthwash, antioxidant mouthwash, or ozone therapy. Reactive oxygen metabolites (ROMs), periodontal parameters, and glycated hemoglobin were measured at baseline and then at 1, 3, and 6 months after. Results: At baseline, all patients presented with pathologic levels of plasmatic ROM (388 ± 21.36 U CARR), higher than the normal population. Probing depth, plaque index, and bleeding on probing values showed significant clinical improvements after treatment, accompanied by significant reductions of plasma ROM levels (p < 0.05). At the 6-month evaluation, the mean ROM relapsed to 332 ± 31.76 U CARR. Glycated hemoglobin decreased significantly (∆ = −0.52 units) after treatment. Both the test groups showed longer-lasting improvements of periodontal parameters. Conclusion: In diabetic patients, periodontal treatment was effective at reducing plasma ROM, which is an indicator of systemic oxidative stress and inflammation. The treatment of periodontal infection might facilitate glycemic control and decrease systemic inflammation.

Clinical Significance of Serum Levels of ROM (Reactive Oxygen Metabolites) in Patients With Rheumatoid Arthritis Treated With Biologic Agents as a Predictor for the CDAI-, SDAI-, and Boolean-Remission

We previously showed that reactive oxygen metabolites (ROM) serum levels were associated with the DAS28 in patients with rheumatoid arthritis (RA). In this study, we aimed to investigate whether ROM would be predictive of the CDAI-, SDAI- or Boolean-remission. Fifty-one biologic agents (BA)-naïve RA patients were included in this observational study. Associations between ROM, C-reactive protein (CRP), MMP (matrix metalloproteinase)-3, DAS28-ESR, CDAI, SDAI, and health assessment questionnaire (HAQ) at 12 weeks and the DAS28-, CDAI-, SDAI-, and Boolean-remission at 52 weeks were investigated. The DAS28-, CDAI-, SDAI- and Boolean-remission rates at 52 weeks were 66.7, 52.9, 54.9 and 54.9%, respectively. A multivariate logistic regression analysis revealed that ROM and HAQ at 12 weeks were associated with the CDAI-, SDAI- and Boolean-remission at 52 weeks. Receiver operating characteristic (ROC) analyses demonstrated that the cut-off value for CDAI remission was 389.5 U.Carr, and that for SDAI and Boolean remission was 389.5 U.Carr. ROM at 12 weeks of initial treatment with BAs was a predictor for the CDAI-, SDAI-, and Boolean-remission at 52 weeks. Serum levels of ROM may be a useful biomarker in the current treatment strategy aiming at the early remission of RA.

Raising the ‘Good’ Oxidants for Immune Protection

Redox medicine is a new therapeutic concept targeting reactive oxygen species (ROS) and secondary reaction products for health benefit. The concomitant function of ROS as intracellular second messengers and extracellular mediators governing physiological redox signaling, and as damaging radicals instigating or perpetuating various pathophysiological conditions will require selective strategies for therapeutic intervention. In addition, the reactivity and quantity of the oxidant species generated, its source and cellular location in a defined disease context need to be considered to achieve the desired outcome. In inflammatory diseases associated with oxidative damage and tissue injury, ROS source specific inhibitors may provide more benefit than generalized removal of ROS. Contemporary approaches in immunity will also include the preservation or even elevation of certain oxygen metabolites to restore or improve ROS driven physiological functions including more effective redox signaling and cell-microenvironment communication, and to induce mucosal barrier integrity, eubiosis and repair processes. Increasing oxidants by host-directed immunomodulation or by exogenous supplementation seems especially promising for improving host defense. Here, we summarize examples of beneficial ROS in immune homeostasis, infection, and acute inflammatory disease, and address emerging therapeutic strategies for ROS augmentation to induce and strengthen protective host immunity.

Free radical reactions in socially significant infectious diseases: HIV infection, hepatitis, tuberculosis

The analysis of current literature data on the study of the features of the course of free-radical reactions, as well as the state of the antioxidant defense system at socially significant infectious diseases HIV infection, hepatitis, tuberculosis was carried out. The role of this kind of reaction in the genesis and progression of socially significant infections a long time has been studied. Foreign studies of recent years have been focused on the identification of specific markers of oxidative and carbonyl stress, which make it possible to identify the redox imbalance of the cell under conditions of infection and target affect it to modulate the activity of the main transcription factors of viral proteins and the bacteria pathogenicity. Numerous sources indicate the involvement of active oxygen metabolites in a wide range of events in infected cells and tissues, including neoplastic transformation processes. These biochemical markers can be used as additional criteria for monitoring the progression of infection. At the same time, noticeable gaps in this area there are that may become the goal of future research. The issues of changing free radical reactions depending on gender, age, place of residence of patients remain practically unstudied. There is little data about intensity of oxidative stress in patients of reproductive age with HIV, hepatitis B and C, and pulmonary tuberculosis, as well as the relationship of antioxidant deficiency with reproductive disorders in conditions of infection. These data could serve as the basis for the development of pathogenetically substantiated methods for the correction of socially significant infectious diseases. Modulation of the production of reactive oxygen metabolites and oxidative stress is a potentially new pharmacological approach to reduce the effects of viral and bacterial exposure.