Mild Coronavirus Disease 2019 (COVID-19) Is Marked by Systemic Oxidative Stress: A Pilot Study

Oxidative stress has been implicated to play a critical role in the pathophysiology of coronavirus disease 2019 (COVID-19) and may therefore be considered as a relevant therapeutic target. Serum free thiols (R-SH, sulfhydryl groups) comprise a robust marker of systemic oxidative stress, since they are readily oxidized by reactive oxygen species (ROS). In this study, serum free thiol concentrations were measured in hospitalized and non-hospitalized patients with COVID-19 and healthy controls and their associations with relevant clinical parameters were examined. Serum free thiol concentrations were measured colorimetrically (Ellman’s method) in 29 non-hospitalized COVID-19 subjects and 30 age-, sex-, and body-mass index (BMI)-matched healthy controls and analyzed for associations with clinical and biochemical disease parameters. Additional free thiol measurements were performed on seven serum samples from COVID-19 subjects who required hospitalization to examine their correlation with disease severity. Non-hospitalized subjects with COVID-19 had significantly lower concentrations of serum free thiols compared to healthy controls (p = 0.014), indicating oxidative stress. Serum free thiols were positively associated with albumin (St. β = 0.710, p < 0.001) and inversely associated with CRP (St. β = −0.434, p = 0.027), and showed significant discriminative ability to differentiate subjects with COVID-19 from healthy controls (AUC = 0.69, p = 0.011), which was slightly higher than the discriminative performance of CRP concentrations regarding COVID-19 diagnosis (AUC = 0.66, p = 0.042). This study concludes that systemic oxidative stress is increased in patients with COVID-19 compared with healthy controls. This opens an avenue of treatment options since free thiols are amenable to therapeutic modulation.

Novel Redox Tests for Maillard Abuse-Induced Redox Imbalance: a Pilot Single Case Paradigm Analyzing Dietary Oxidized-Browned Foods and Their Instant-Influence on Oral-Intestinal, Extracellular, and Intracellular Systemic Oxidative and Reductive Stress and Eventual Association with COVID-19 Sepsis and Other Leading Causes of Morbidity and Mortality Globally

The public health hazards associated with Maillard end-products such as melanoidins and advanced lipoxidation end-products (ALEs) and advanced glycation end-products (AGEs), intermediary Maillard reaction creations, include most of the leading causes of morbidity and mortality globally. At the same time, only a few clinicians understand the intricacies linking redox biophysics and disease to humans and animals, explained here and in companion articles in simple to conceptualize terms. Maillard abuse causes increased systemic oxidative stress (SOS: pE-> pH+), an accelerant to the fatal vascular complications of type 1 diabetes. Maillard abuse-induced SOS (pE-> pH+) is also linked to type 2 diabetes, thyroid disorders, polycystic ovary syndrome, low testosterone, and osteoporosis. Many studies have shed light on exotic, intricate, and pricey markers to test extracellular and intracellular Maillard reaction-induced redox imbalance. And their corresponding influence on soluble and cell receptor signaling and the Maillard-induced redox-based diseases and deaths they cause. Inconclusive and pricey new markers for measuring extracellular and intracellular redox balance and imbalance cost thousands of US Dollars (USD) per in vivo assay. The author presents seven extracellular and intracellular redox markers costing less than 150 USD per in vivo assay, using standard laboratory tests available to medical centers worldwide. A PubMed search revealed no studies testing colas, pizza, burgers, and wings-specific intra-day Maillard-rich food binges on TSH, TG/HDL ratio (THR), VLDL/HDL ratio (VHR), LDL/HDL ratio (LHR), and urine pH+ extracellular redox markers, and neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) intracellular redox indicators. The objective of this pilot single case study is to test the feasibility of replication on a much larger scale. The second objective is to analyze the potential influence or lack of impact of Maillard intermediate and end-products on oral-intestine, corporal extracellular, and intracellular redox biophysics, soluble and cell receptor signaling, immunosuppression, inflammation, and risk for developing one or more of the leading causes of morbidity and mortality worldwide at three targeted intraday-pH+ points. The participant met inclusion criteria and drank acidic tide-inducing Maillard-rich colas to prompt an intra-oral-intestinal and the body’s extracellular systemic oxidative stress (SOS: pE-> pH+)-associated plasma acidic-tide. And had blood drawn for CBC with differential and platelet count, comprehensive metabolic panel, lipid panel, and TSH, and provided a sample for a routine urinalysis after an at-home confirmation of extracellular acidic-tide using ‘Just Fitter pH Test Strips pH 4.5 – pH 9.0.’ In a concerted attempt to reach an at-home urine pH+ strip value of 5.5, the top of the 4.5 to 5.5 urine and 7.35 to 7.38 blood systemic oxidative stress range (SOS: pE-> pH+). Before driving to the lab to give blood and urine samples for CBC with differential, comprehensive metabolic panel, lipid panel, TSH, and routine urinalysis. A similar procedure occurred to consuming mainly alkaline-botanical pizza, peanut butter shake, stronger alkaline tide-inducing acidic bacon double cheeseburgers and twelve fried chicken wings. The move from cola-associated urine pH+ 6 to pizza-associated pH+ 6.5 within the prime systemic energy PSE (pE- = pH+) urine pH+ range increased oral-intestinal, extracellular, and intracellular SOS by a factor of 50. The move from pizza-associated urine pH+ 6.5 to burgers and wings-associated pH+ 7.0 within the systemic reductive stress (SRS: pE-< pH+) urine pH+ range of 6.7 to 7.7, increased oral-intestinal, extracellular, and intracellular SOS (SOS: pE- > pH+) by a massive score of 556. This pilot study warrants reproduction on a larger scale with similarly healthy participants with elevated antioxidant tone. Such Maillard-intense trials require safe inclusionary criteria that limit initial subject sample pools to the equivalent of less than 25% of healthy females and males 8 to 80 years of age within or close to their ideal body mass indices and waist-to-height ratios.

Novel Redox Tests for Maillard Abuse-Induced Redox Imbalance: a Pilot Single Case Paradigm Analyzing Dietary Oxidized-Browned Foods and Their Instant-Influence on Oral-Intestinal, Extracellular, and Intracellular Systemic Oxidative and Reductive Stress and Eventual Association with COVID-19 Sepsis and Other Leading Causes of Morbidity and Mortality Globally

The public health hazards associated with Maillard end-products such as melanoidins and advanced lipoxidation end-products (ALEs) and advanced glycation end-products (AGEs), intermediary Maillard reaction creations, include most of the leading causes of morbidity and mortality globally. At the same time, only a few clinicians understand the intricacies linking redox biophysics and disease to humans and animals, explained here and in companion articles in simple to conceptualize terms. Maillard abuse causes increased systemic oxidative stress (SOS: pE-> pH+), an accelerant to the fatal vascular complications of type 1 diabetes. Maillard abuse-induced SOS (pE-> pH+) is also linked to type 2 diabetes, thyroid disorders, polycystic ovary syndrome, low testosterone, and osteoporosis. Many studies have shed light on exotic, intricate, and pricey markers to test extracellular and intracellular Maillard reaction-induced redox imbalance. And their corresponding influence on soluble and cell receptor signaling and the Maillard-induced redox-based diseases and deaths they cause. Inconclusive and pricey new markers for measuring extracellular and intracellular redox balance and imbalance cost thousands of US Dollars (USD) per in vivo assay. The author presents seven extracellular and intracellular redox markers costing less than 150 USD per in vivo assay, using standard laboratory tests available to medical centers worldwide. A PubMed search revealed no studies testing colas, pizza, burgers, and wings-specific intra-day Maillard-rich food binges on TSH, TG/HDL ratio (THR), VLDL/HDL ratio (VHR), LDL/HDL ratio (LHR), and urine pH+ extracellular redox markers, and neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) intracellular redox indicators. The objective of this pilot single case study is to test the feasibility of replication on a much larger scale. The second objective is to analyze the potential influence or lack of impact of Maillard intermediate and end-products on oral-intestine, corporal extracellular, and intracellular redox biophysics, soluble and cell receptor signaling, immunosuppression, inflammation, and risk for developing one or more of the leading causes of morbidity and mortality worldwide at three targeted intraday-pH+ points. The participant met inclusion criteria and drank acidic tide-inducing Maillard-rich colas to prompt an intra-oral-intestinal and the body’s extracellular systemic oxidative stress (SOS: pE-> pH+)-associated plasma acidic-tide. And had blood drawn for CBC with differential and platelet count, comprehensive metabolic panel, lipid panel, and TSH, and provided a sample for a routine urinalysis after an at-home confirmation of extracellular acidic-tide using ‘Just Fitter pH Test Strips pH 4.5 – pH 9.0.’ In a concerted attempt to reach an at-home urine pH+ strip value of 5.5, the top of the 4.5 to 5.5 urine and 7.35 to 7.38 blood systemic oxidative stress range (SOS: pE-> pH+). Before driving to the lab to give blood and urine samples for CBC with differential, comprehensive metabolic panel, lipid panel, TSH, and routine urinalysis. A similar procedure occurred to consuming mainly alkaline-botanical pizza, peanut butter shake, stronger alkaline tide-inducing acidic bacon double cheeseburgers and twelve fried chicken wings. The move from cola-associated urine pH+ 6 to pizza-associated pH+ 6.5 within the prime systemic energy PSE (pE- = pH+) urine pH+ range increased oral-intestinal, extracellular, and intracellular SOS by a factor of 50. The move from pizza-associated urine pH+ 6.5 to burgers and wings-associated pH+ 7.0 within the systemic reductive stress (SRS: pE-< pH+) urine pH+ range of 6.7 to 7.7, increased oral-intestinal, extracellular, and intracellular SOS (SOS: pE- > pH+) by a massive score of 556. This pilot study warrants reproduction on a larger scale with similarly healthy participants with elevated antioxidant tone. Such Maillard-intense trials require safe inclusionary criteria that limit initial subject sample pools to the equivalent of less than 25% of healthy females and males 8 to 80 years of age within or close to their ideal body mass indices and waist-to-height ratios.

Predictors of 5-year survival in patients with chronic heart failure and reduced left ventricular ejection fraction depending on the presence of type 2 diabetes mellitus

The aim – to determine the predictors of 5-year survival of patients with CHF and reduced LV EF depending on the presence of type 2 diabetes mellitus.Materials and methods. 490 case histories of patients in the period from 2011 to 2018 with CHF, 40–80 years of age (median – 64 years), II–IV NYHA functional class, LVEF ≤ 40 % were analyzed. For the analysis of all patients with CHF and reduced LV EF were divided into two groups: Group I included 338 (69 %) patients without diabetes mellitus type 2, group II consisted of 152 (31 %) patients diagnosed with diabetes mellitus type 2. To measure the values ​​of the independent predictors, we calculated the value of the odds ratio (OR) with a 95 % confidence interval. To determine predictors of mortality/survival of the studied patients, was calculated the Хі-square criterion. Additionally, we calculated the estimate of the frequency difference between the groups, the odds ratio, the confidence interval for the odds ratio, the Pearson correlation coefficient r, for all the calculated characteristics we determined the probability of error of the first kind p. As a result, we formed a final table of indicators-predictors of mortality/survival of patients with CHF with reduced LV EF with and without diabetes mellitus type 2 for which there is a statistical relationship between mortality / survival and the studied indicator.Results and discussion. In patients without diabetes, many indicators are associated with the prognosis of long-term survival. These include hemodynamic parameters (heart rate, the left atrium size (LV) and indexed left ventricular (LV) volumes, LV myocardial mass index, right ventricular size (RV) and LV ejection fraction, renal function parameters (microalbuminuria (UIA), glomerular filtration rate (GFR), urea nitrogen), systemic inflammatory marker (C-reactive protein (CRP)), markers of systemic oxidative stress (myeloperoxidase, citrulline, uric acid) and antioxidant defence – SOD, as well as the N-terminal fragment of the precursor of natriuretic peptide (NT-proBNP), flow-dependent vasodilatory response (FDVR), high-density lipoprotein cholesterol (HDL), insulin and the relative content of lymphocytes in the blood. Patients with diabetes had significantly fewer such predictors: in addition to parameters of intracardiac hemodynamics and heart modeling, other significant predictors of 5-year survival were daily UIA level, CRP, SOD, HDL, insulin and the lymphocyte level.Conclusions. Quantitative predictors of poor 5-year survival prognosis among patients with CHF and reduced LV EF with and without concomitant diabetes mellitus type 2 are parameters of heart remodeling, LV systolic function-EF, UIA level, antioxidant stress marker (SOD), HDL level, blood lymphocytes and the level of circulating insulin. Patients without diabetes are characterized by a wider range of poor long-term survival predictors, which include indicators of renal nitrogen function, markers of systemic oxidative stress (myeloperoxidase, citrulline, uric acid), flow-dependent vasodilatory response and circulating NT-proBNP. The determined quantitative predictors can be used in algorithms of individual prediction of the course of CHF and reduced LV EF, which should be created separately for patients with and without concomitant diabetes mellitus type 2

Chemotherapy agents reduce protein synthesis and ribosomal capacity in myotubes independent of oxidative stress

Chemotherapeutic agents (CAs) are first-line antineoplastic treatments in a wide variety of cancers. These agents can induce oxidative stress and promote muscle loss. CAs trigger local and systemic oxidative stress by increasing mitochondrial reactive oxygen species (ROS) and thereby stimulate protein breakdown. However, whether CAs can directly impact muscle protein synthesis independent of ROS production is currently unknown. To address this problem, first, we identified the mechanism by which oxidative stress impairs myotube protein synthesis. Transient elevations in ROS production resulted in protein synthesis deficits, reduced ribosomal (r)RNA levels and increased rRNA oxidation. We then investigated the effects of CAs on protein synthesis in the absence of detectable elevations in ROS levels (sub-ROS). Paclitaxel (PTX), Doxorubicin (DXR) and Marizomib (Mzb) diminished protein synthesis and ribosomal capacity, and also impaired transcription of the rRNA genes (rDNA). These results indicate that while oxidative stress disrupted protein synthesis by compromising ribosome quantity and quality, CAs at sub-ROS doses also impaired protein synthesis and ribosomal capacity by reducing rDNA transcription. Therefore, CAs can negatively modulate myotube protein synthesis in a ROS-independent manner by altering the capacity for protein synthesis.

The Effect of Lifestyle Intervention on Systemic Oxidative Stress in Women with Obesity and Infertility: A Post-Hoc Analysis of a Randomized Controlled Trial

We aimed to study whether lifestyle intervention could reduce systemic oxidative stress (OS) and the association between OS and cardiometabolic outcomes in women with obesity and infertility. From 2009 to 2012, infertile women with a BMI ≥ 29 kg/m2 were randomly assigned to a six-month lifestyle intervention followed by infertility treatment (N = 289) or to prompt infertility treatment (N = 285). Fasting serum free thiols (FT) concentrations were determined by colorimetry at baseline, at three and six months after randomization. Generalized estimating equations and restricted cubic spline regressions were used to estimate mean differences in serum FT levels between groups and to explore associations between serum FT levels and cardiometabolic outcomes. Baseline serum FT levels did not differ between the two groups (N = 203 in the intervention group vs. N = 226 in the control group, 222.1 ± 48.0 µM vs. 229.9 ± 47.8 µM, p = 0.09). Body weight decreased by 3.70 kg in the intervention group compared with the control group at six months (95% confidence interval [CI]: −7.61 to 0.21, p = 0.06). No differences in serum FT levels were observed between groups at either three months (N = 142 vs. N = 150, mean differences: −1.03 µM, 95% CI: −8.37 to 6.32, p = 0.78) or six months (N = 104 vs. N = 96, mean differences: 2.19 µM, 95% CI: −5.90 to 10.28, p = 0.60). In a pooled analysis of all available measurements, triglycerides (crude B: 5.29, 95% CI: 1.08 to 9.50, p = 0.01), insulin (crude B: 0.62, 95% CI: 0.26 to 0.98, p = 0.001), and homeostasis model assessment of insulin resistance (crude B: 2.50, 95% CI: 1.16 to 3.38, p < 0.001) were positively associated with serum FT levels. High-sensitivity C-reactive protein (hs-CRP) was negatively associated with serum FT levels (crude B: −0.60, 95% CI: −1.11 to −0.10, p = 0.02). The change in hs-CRP during the lifestyle intervention was strongly and inversely associated with serum FT levels (crude B: −0.41, 95% CI: −0.70 to −0.13, p = 0.005). No significant deviations from linear associations were observed between serum FT and hs-CRP. We do not observe an improvement in systemic OS in women with obesity and infertility with modest weight loss. There were potential associations between OS and biomarkers of cardiometabolic health. Trial registration: This trial was registered on 16 November 2008 at the Dutch trial register (NTR1530).