scholarly journals Ceramide Levels and COVID-19 Respiratory Distress, a Causal Relationship

2021 ◽  
Author(s):  
Mehran Khodadoust
Keyword(s):  
Respiratory Distress ◽  
Causal Relationship ◽  
Fold Increase ◽  
Plasma Samples ◽  
Total Plasma ◽  
Lipidomic Analysis ◽  
Distress Symptoms ◽  
Concentration Dependency ◽  
Ceramide Synthesis ◽  
Total Plasma Concentration

Abstract A causal relationship between plasma ceramide concentration and respiratory distress symptoms in COVID-19 patients is presented. In this study, plasma samples of 52 individuals infected with COVID-19 were utilized in a lipidomic analysis. Lipids belonging to the ceramide class exhibited a 400-fold increase in total plasma concentration in infected patients. Further analysis led to the demonstration of concentration dependency for severe COVID-19 respiratory symptoms in a subclass of ceramides. The subclasses Cer(d18:0/24:1), Cer(d18:1/24:1), and Cer(d18:1/22:0) were shown to be increased by 48-, 40-, and 33-fold, respectively, in infected plasma samples and to 116-, 91- and 50-fold, respectively, in plasma samples with respiratory distress. Hence, monitoring plasma ceramide concentration, targeting ceramide synthesis, its salvage and its regulatory mechanisms are validated approaches towards enhancing survival from COVID-19 respiratory distress.

scholarly journals Ceramide Levels and Covid-19 Respiratory Distress, a Causal Relationship

2021 ◽  
Author(s):  
Mehran Khodadoust
Keyword(s):  
Respiratory Distress ◽  
Causal Relationship ◽  
Fold Increase ◽  
Plasma Samples ◽  
Total Plasma ◽  
Lipidomic Analysis ◽  
Distress Symptoms ◽  
Concentration Dependency ◽  
Ceramide Synthesis ◽  
Total Plasma Concentration

Abstract A causal relationship between plasma ceramide concentration and Covid-19 patients with respiratory distress symptoms is presented. In this study, plasma samples of 52 individuals infected with Covid-19 were utilized in a lipidomic analysis. Lipids belonging to ceramide class exhibited a 400-fold increase in total plasma concentration in infected patients. Further analysis lead to demonstration of concentration dependency, for severe Covid-19 respiratory symptoms, in a subclass of ceramides. The subclasses Cer(d18:0/24:1), Cer(d18:1/24:1), and Cer(d18:1/22:0) are shown to be increased by 48, 40, and 33–folds respectively in infected plasma samples, and to 116, 91 and 50-folds in plasma samples with respiratory distress. Hence, monitoring of plasma ceramide concentration, targeting ceramide synthesis, its salvage and its regulatory mechanisms, are validated approach towards enhancing survival from Covid-19 respiratory distress.

scholarly journals Ceramide Levels and Covid-19 Respiratory Distress, a Causal Relationship

2021 ◽  
Author(s):  
Mehran Khodadoust
Keyword(s):  
Respiratory Distress ◽  
Causal Relationship ◽  
Fold Increase ◽  
Plasma Samples ◽  
Total Plasma ◽  
Lipidomic Analysis ◽  
Distress Symptoms ◽  
Concentration Dependency ◽  
Ceramide Synthesis ◽  
Total Plasma Concentration

Abstract A causal relationship between plasma ceramide concentration and Covid-19 patients with respiratory distress symptoms is presented. Hence, monitoring of plasma ceramide concentration, targeting ceramide synthesis, its salvage and its regulatory mechanisms, are validated approach towards enhancing survival from Covid-19 respiratory distress. In this study, plasma samples of 52 individuals infected with Covid-19 were utilized in a lipidomic analysis. Lipids belonging to ceramide class exhibited a 400-fold increase in total plasma concentration in infected patients. Further analysis lead to demonstration of concentration dependency, for severe Covid-19 respiratory symptoms, in a subclass of ceramides. The subclasses Cer(d18:0/24:1), Cer(d18:1/24:1), and Cer(d18:1/22:0) are shown to be increased by 48, 40, and 33–folds respectively in infected plasma samples, and to 116, 91 and 50-folds in plasma samples with respiratory distress.

scholarly journals Inferring a causal relationship between ceramide levels and COVID-19 respiratory distress

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mehran M. Khodadoust
Keyword(s):  
Respiratory Distress ◽  
Causal Relationship ◽  
Respiratory Symptoms ◽  
Fold Increase ◽  
Plasma Samples ◽  
Total Plasma ◽  
Lipidomic Analysis ◽  
Distress Symptoms ◽  
Concentration Dependency ◽  
Total Plasma Concentration

AbstractA causal relationship between plasma ceramide concentration and respiratory distress symptoms in COVID-19 patients is inferred. In this study, plasma samples of 52 individuals infected with COVID-19 were utilized in a lipidomic analysis. Lipids belonging to the ceramide class exhibited a 400-fold increase in total plasma concentration in infected patients. Further analysis led to the demonstration of concentration dependency for severe COVID-19 respiratory symptoms in a subclass of ceramides. The subclasses Cer(d18:0/24:1), Cer(d18:1/24:1), and Cer(d18:1/22:0) were shown to be increased by 48-, 40-, and 33-fold, respectively, in infected plasma samples and to 116-, 91- and 50-fold, respectively, in plasma samples with respiratory distress. Hence, monitoring plasma ceramide concentration, can be a valuable tool for measuring effects of therapies on COVID-19 respiratory distress patients.

Long-Term Performance and Stability of Molecular Shotgun Lipidomic Analysis of Human Plasma Samples

2013 ◽  
Vol 85 (18) ◽  
pp. 8757-8763 ◽  
Author(s):  
Laura A. Heiskanen ◽  
Matti Suoniemi ◽  
Hung Xuan Ta ◽  
Kirill Tarasov ◽  
Kim Ekroos
Keyword(s):  
Human Plasma ◽  
Plasma Samples ◽  
Lipidomic Analysis ◽  
Human Plasma Samples ◽  
Long Term Performance ◽  
Term Performance

scholarly journals Quantifying Oxidized Lipids in Oven Fried and Deep Fried Potatoes: A Three-Way Analysis by LOI, Chemical Assays, and Lipidomics

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 789-789
Author(s):  
Traycie Williams ◽  
Paul Plummer ◽  
Mandy Blackburn ◽  
Timothy Garrett ◽  
Vasilis Vasiliou ◽  
...  
Keyword(s):  
Lipid Oxidation ◽  
Fold Increase ◽  
Oxidized Lipids ◽  
Walnut Oil ◽  
Lipidomic Analysis ◽  
Funding Sources ◽  
Relative Value ◽  
Conjugated Triene ◽  
Fried Potatoes ◽  
Good Agreement

Abstract Objectives Standard chemical methods that determine oxidized lipids in foods are laborious and require toxic chemicals. Our goal was to develop a mathematical lipid oxidation index (LOI) to predict oxidized lipid content of oven fried (OF) and deep fried (DF) potatoes and compare it to standard chemical assays and redox lipidomic analyses. Methods We calculated the LOI value of each recipe using a mathematical formula which consisted of the parameters of 16 nutrients, time and temperature. Next, we OF and DF potatoes in soy, olive, and walnut oils and then extracted oil from the cooked potatoes using the modified Hara and Radin method. We assayed samples of each oil to quantify the conjugated diene (CD), conjugated triene (CT), peroxide (PV), acid (AV), and p-Anisidine (p-Ad) values. In addition, aliquots of each oil sample were sent to collaborators to determine the relative value of oxidized lipids by mass spectrometry and lipidomic informatics. Results Overall, the chemical assays demonstrated that oven frying promoted significantly more oxidation than deep frying. Potatoes OF in walnut oil had greater mean CD (24.1 ± 0.44 vs 19.45 ± 0.06), CT (16.43 ± 0.25 vs 15.67 ± 0.12), AV (0.29 ± 0.01 vs 0.14 ± 0.003), PV (361 ± 7.6 vs 200 ± 6.06), and p-Ad (0.50 ± 0.03 vs 0.14 ± 0.01) when compared to DF potatoes (P ≤ 0.05). This increase in lipid oxidation was not consistent for potatoes prepared with soy and olive oils. LOI predicted a two-fold increase in lipid oxidation in OF potatoes as compared to DF potatoes no matter the type of oil (soy: 308 vs 150; olive: 319 vs; walnut: 330 vs 161). Finally, lipidomic analysis revealed a similar trend in the relative amounts of total oxidized lipids in OF potatoes (soy oil: 24% vs 12%; olive oil: 22% vs 7%; walnut oil 31% vs 17%) and was used to tentatively annotate over 3000 unique oxidized lipids. Conclusions This preliminary study demonstrates that two of the three methods, LOI and lipidomic analysis, are in good agreement in quantifying lipid oxidation in OF and DF potatoes. However, the suboptimal agreement of the chemical assays suggests that the parameters of LOI require further examination. Funding Sources MP is funded by a grant from the Research Dietetic Practice Group (RDPG)/Sugar Association. TW is funded by the Regina Myers McClain Foundation at UCM for his work as a research assistant.

scholarly journals Sex-related differences in human plasma NAD+/NADH levels depend on age

2021 ◽  
Author(s):  
Luisa Schwarzmann ◽  
Rainer Ullrich Pliquett ◽  
Andreas Simm ◽  
Babett Bartling
Keyword(s):  
Older Women ◽  
Human Plasma ◽  
Nicotinamide Adenine Dinucleotide ◽  
Pulse Wave ◽  
Plasma Samples ◽  
Total Plasma ◽  
Men And Women ◽  
Nadh Ratio ◽  
Metabolic Reactions ◽  
Two Parameters

Nicotinamide adenine dinucleotide (NAD) is coenzyme in metabolic reactions and cosubstrate in signaling pathways of cells. While the intracellular function of NAD is well described, much less is known about its importance as extracellular molecule. Moreover, there is only little information about the concentration of extracellular NAD and the ratio between its oxidized (NAD+) and reduced (NADH) form in human. Therefore, our study aimed at the analysis of total NAD and NAD+/NADH ratio in human plasma depending on sex and age. Firstly, an enzymatic assay was established for detecting NAD+ and NADH in human plasma samples. Then, plasma NAD was analyzed in 205 probands without severe diseases (91 men, 114 women) being 18 to 83 years old. The total plasma NAD concentration was determined with median 1.34 µM (0.44 – 2.88 µM) without difference between men and women. Although the amounts of NAD+ and NADH were nearly balanced, women had higher plasma NAD+/NADH ratios than men (median 1.33 vs. 1.09, P < 0.001). The sex-related difference in the plasma NAD+/NADH ratio reduces with increasing age, an effect that was more obvious for two parameters of the biological age (skin autofluorescence, brachial-femoral pulse wave velocity) than for the chronological age. However, plasma values for total NAD and NAD+/NADH ratio did not generally alter with increasing age. In conclusion, human plasma contains low micromolar concentrations of total NAD with higher NAD+/NADH redox ratios in adult but not older women compared with same-aged men.

scholarly journals Direct detection of humoral marker corelates of COVID-19, glycated HSA and hyperglycosylated IgG3, by MALDI-ToF mass spectrometry.

2021 ◽  
Author(s):  
Raymond Kruse Iles ◽  
Jason Kruse Iles ◽  
Raminta Zmuidinaite ◽  
Anna Gardiner ◽  
Jonathan Lacey ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Respiratory Distress ◽  
Direct Detection ◽  
Plasma Samples ◽  
Total Blood ◽  
Laser Desorption Mass Spectrometry ◽  
Maldi Tof Ms ◽  
Maldi Tof ◽  
Immune Correlates ◽  
Tof Ms

The prefusion Spike protein of SARS-CoV2 binds advanced glycation end product (AGE) glycated human serum albumin (HSA) and a higher mass, hyperglycosylated/glycated, IgG3, as determined by matrix assisted laser desorption mass spectrometry (MALDI-ToF MS). We set out to investigate if the total blood plasma of patients who had recovered from acute respiratory distress as a result of COVID-19, contained more glycated HSA and higher mass (glycosylated/glycated) IgG3 than those with only clinically mild or asymptomatic infections. A direct dilution and disulphide bond reduction method was development and applied to plasma samples from SARS-CoV2 seronegative (N = 30) and seropositive (N = 31) healthcare workers and 38 convalescent plasma samples from patients who had been admitted with acute respiratory distress syndrome (ARDS) associated with COVID-19. Patients recovering from COVID-19 ARDS had significantly higher mass, AGE-glycated HSA and higher mass IgG3 levels. This would indicate that increased levels and/or ratios of hyper-glycosylation (probably terminal sialic acid) IgG3 and AGE glycated HSA may be predisposition markers for development of ARDS as a result of COVID-19 infection. Furthermore, rapid direct analysis of plasma samples by MALDI-ToF MS for such humoral immune correlates of COVID-19 presents a feasible screening technology for the most at risk; regardless of age or known health conditions.

Specificity of Antisera to Human Fibrinopeptide A Used in Clinical Fibrinopeptide A Assays

1976 ◽  
Vol 35 (01) ◽  
pp. 101-109 ◽  
Author(s):  
Hymie L Nossel ◽  
Vincent P Butler ◽  
George D Wilner ◽  
Robert E Canfield ◽  
Elizabeth J Harfenist
Keyword(s):  
Fold Increase ◽  
Clinical Results ◽  
The Other ◽  
Antigenic Determinants ◽  
Fibrinopeptide A ◽  
Plasma Samples ◽  
Practical Consequence ◽  
Amino Terminal ◽  
Molar Basis ◽  
Specific Antisera

SummaryDistinction between fibrinopeptide A (FPA) and larger polypeptides containing the FPA sequence is critical for the interpretation of clinical results with FPA immunoassay methods. Therefore, the immunochemical reactivity of 14 rabbit anti-FPA sera with six different FPA containing antigens was studied in detail. Antigens tested included: fibrinogen; fragment E of fibrinogen; the amino-terminal disulfide knot of fibrinogen; Aα 1 (Ala)-51 (Met); Aα l(Ala)-23(Arg); and, FPA. Synthetic partial sequences of FPA were also tested. The 14 FPA-specific antisera were divided into 3 distinct categories with: I, FPA immuno-reactivity of larger polypeptides containing FPA approximately 1/100 of FPA on a molar basis; II, FPA immunoreactivity of the larger polypeptides intermediate between I and III; and III, FPA immunoreactivity of the larger polypeptides approximately equal to that of FPA on a molar basis. The antigenic determinants of a category I antiserum (R 2) are included in Aα 7(Asp)-16(Arg) with Asp(7), Phe(8) and Arg(16) being essential. When attached to FPA, the sequence Gly(17)-Arg(23) decreases the immunoreactivity of FPA with category I antisera 100-fold.The practical consequence of these findings is that, when category III antisera are employed, both FPA and larger FPA-containing polypeptides are equally immunoreactive. Since thrombin treatment of the larger polypeptides does not alter their immunoreactivity, category III antisera cannot discriminate between FPA and the larger polypeptides. On the other hand, with category I antisera, although the immunoreactivity of FPA itself is unaltered by thrombin treatment, larger polypeptides [e.g., Aα l(Ala)-23(Arg)] show a 100-fold increase in immunoreactivity following thrombin treatment and thus can readily be identified and separately quantitated. It is concluded that antisera with the specificity of category I are essential for the specific and accurate measurement of FPA, and for its distinction from larger FPA-containing polypeptides, in clinical plasma samples.

Lovastatin induces synthesis of cholesterol, which acts as a secretagogue of biliary phospholipids in rats

1995 ◽  
Vol 268 (2) ◽  
pp. G242-G250
Author(s):  
W. G. Linscheer ◽  
B. Atreyee ◽  
K. M. Uma ◽  
W. John ◽  
N. Sandor ◽  
...  
Keyword(s):  
Fold Increase ◽  
Hepatic Metabolism ◽  
Biliary Secretion ◽  
Total Plasma ◽  
Elastic Light Scattering ◽  
Phosphocholine Cytidylyltransferase ◽  
Hepatic Microsomes ◽  
Scattering Measurements ◽  
Rate Limiting ◽  
Hepatic Synthesis

The effects of treatment with lovastatin (LS), a hypocholesterolemic drug, on hepatic metabolism of cholesterol (CH) and phosphatidylcholine (PC) were studied in rats. Hepatic synthesis of CH was increased, as previously reported by our laboratory. Total plasma CH was increased, and biliary secretion of CH was raised fourfold, but biliary secretion of bile salts was not affected. Because CH is practically insoluble in an aqueous milieu, we tested the hypothesis that excessive CH is solubilized and secreted into bile as cholesterol-phospholipid (CH-PL) vesicles. The effects of LS-induced increase in CH synthesis on hepatic metabolism of PC after 7 days of oral LS treatment (17.5 mg/day) were studied. Our results showed accelerated synthesis of PC and increased biliary secretion of newly formed PC into bile, as evidenced by the following. 1) Phosphocholine cytidylyltransferase (EC 2.7.7.15) activity, the rate limiting enzyme in the synthesis of PC, increased 2.5-fold in the hepatic microsomes of the hepatocytes. 2) After intravenous administration of [14C]choline, a precursor of PC, [14C]PC increased significantly in bile. 3) Biliary output of PC increased twofold. 4) Quasi-elastic light scattering measurements of bile showed a 3.5-fold increase in intensity of the CH-PL vesicles, indicating higher concentrations of CH-PL vesicles, but there was no change in the intensity of the micelles. These observations support the hypothesis that PC synthesis was enhanced as a transport mechanism for secretion of the excessive amounts of cholesterol from the hepatocytes into bile as CH-PC vesicles.

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